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3,500 | 68,417 | To compare the B cell repertoire of normal individuals and patients with rheumatoid arthritis (RA) and, specifically, to identify precursor B cells with the potential to secrete rheumatoid factor (RF) and to understand the T helper cell requirements for the production of this autoantibody.
Frequencies of precursors of IgM-, IgG-, and RF-producing B cells were measured in a limiting-dilution system. Two distinct sources of T cell help were compared. T cell help was provided by anti-CD3-activated CD4+ human T cell clones, or T cell-B cell interaction was facilitated by the bacterial super-antigen staphylococcal enterotoxin D (SED).
A subset of 2-14% of peripheral blood B cells secreted IgM and IgG in SED-driven cultures. The SED-responsive B cell subpopulation was present at 10 times higher frequency in normal donors compared with RA patients. However, the repertoires were very similar, particularly for RF+ precursors, which represented approximately one-third of all SED-responsive B cells. In normal individuals, most of these RF+ precursor B cells did not respond to anti-CD3-activated T helper cells, with only a very small fraction of B cells activated by anti-CD3-driven helper cells maturing into RF-secreting B cells (from 1 of 182 to 1 of 889 IgM-producing B cells). This subset was expanded approximately 50-fold in RA patients. | Normal subjects and RA patients share a pool of B cells which secrete RF when activated in the presence of SED and T helper cells. These B cells are frequent and obviously anergic in normal individuals. The B cell subset with the potential to produce RF when help is provided in noncognate T-B interaction (anti-CD3-driven T cells) is considerably expanded in RA patients, probably reflecting an increased responsiveness of such B cells to helper signals. |
3,501 | 21,792 | Bone deformities in the varus osteoarthritic knee may influence soft-tissue balancing and therefore knee correctability. The hypothesis of the present study was that the grade of coronal plane knee deformity may influence directly knee correctability along the entire range of motion from 0° to 90°. Tibial and femoral epiphyseal bone deformities were also analyzed to determine which kind had the greater impact on knee correctability.
A coronal plane deformity radiographic assessment and an intraoperative correctability assessment using computer-assisted surgery were performed on 118 varus osteoarthritic knees undergoing total knee arthroplasty. Knees were divided into groups taking into account the kind of bone deformity (tibial, femoral, and combined).
A significant inverse correlation was found between coronal plane deformity and knee correctability at every 10 degrees of flexion. Correlation was strong at 0° and progressively got weaker at further flexion angles. According to literature, knees with a varus deformity >10° were rarely correctable in full extension, but often correctable in flexion, whereas knees with varus deformity >15° showed to be almost never correctable. Combined deformity group had a significantly lower rate of correctability along the entire range of motion. | The severity of varus knee malalignment always influenced knee correctability with the knee in full extension, in further flexion (20°-60°), correctability was mildly affected. Isolated tibial epiphyseal deformity and combined epiphyseal deformity have the greatest impact on knee correctability. |
3,502 | 17,114 | Determine the presence and assess the extent of fatty infiltration of the minor salivary glands (SG) of primary SS patients (pSS) as compared to those with non-SS sicca (nSS).
Minor SG biopsy samples from 134 subjects with pSS (n = 72) or nSS (n = 62) were imaged. Total area and fatty replacement area for each glandular cross-section (n = 4-6 cross-sections per subject) were measured using Image J (National Institutes of Health, Bethesda, MD). The observer was blinded to subject classification status. The average area of fatty infiltration calculated per subject was evaluated by logistic regression and general linearized models (GLM) to assess relationships between fatty infiltration and clinical exam results, extent of fibrosis and age.
The average area of fatty infiltration for subjects with pSS (median% (range) 4.97 (0.05-30.2)) was not significantly different from that of those with nSS (3.75 (0.087-41.9). Infiltration severity varied widely, and subjects with fatty replacement greater than 6% were equivalently distributed between pSS and nSS participants (χ | Fatty infiltration is an age-associated phenomenon and not a selective feature of Sjögren's syndrome. Sicca patients who do not fulfil pSS criteria have similar rates of fatty infiltration of the minor SG. |
3,503 | 1,585 | While anatomic total shoulder arthroplasty (TSA) has historically been considered the ideal treatment for end-stage glenohumeral osteoarthritis, reverse shoulder arthroplasty (RSA) has recently gained popularity. With substantial differences in implant design and cost between TSA and RSA, further investigation of outcomes and value is needed to support recent trends. The purpose of this study was to use the average and incremental cost-effectiveness ratio (ACER and ICER) and the procedure value index (PVI) to examine differences in outcomes and value between TSA and RSA for treatment of glenohumeral osteoarthritis with an intact rotator cuff.
We performed a retrospective matched-cohort study of patients treated with primary shoulder arthroplasty for osteoarthritis with an intact rotator cuff who had a minimum 2-year follow-up. Outcome measures analyzed included the Simple Shoulder Test (SST), American Shoulder and Elbow Surgeons (ASES) questionnaire, visual analog scale (VAS) for pain, Single Assessment Numeric Evaluation (SANE), and overall satisfaction. Patients treated with TSA were matched 4:1 to those treated with RSA based on sex, age, and preoperative SST score. Value differences between TSA and RSA were calculated. Radiographs were analyzed for preoperative glenoid classification and postoperative radiolucent lines and gross loosening.
Two hundred and fifty-two TSA-treated patients were matched to 63 RSA-treated patients with no significant differences in sex, age, or preoperative SST score. Total hospitalization costs, charges, and reimbursements along with outcome improvements in units of minimal clinically important differences (MCIDs) and patient satisfaction did not differ between the groups. For RSA, the implant cost was significantly higher than that for TSA, but the operating room, anesthesia, and cement costs were lower. The TSA group had a 3.2% rate of gross glenoid loosening and a 2.4% revision rate. There was no loosening or revision in the RSA group. None of the value analytics differed between groups even after inclusion of the outcomes and costs of early TSA revisions.
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. | TSA and RSA demonstrated similar outcomes and value when used to manage glenohumeral osteoarthritis with an intact rotator cuff. |
3,504 | 3,729 | The aim of this study is to describe 4 of the most common autoantibodies against components of the Th/To complex: human POP1 (hPOP1), RPP25, RPP30, and RPP40. We report their prevalence and clinical characteristics in a systemic sclerosis (SSc) population, and determine whether these specificities are associated with cancer.
A case-control study was performed using data from the Johns Hopkins Scleroderma Center Cohort. A total of 804 adult patients with SSc were included; 401 SSc patients with no history of cancer after at least 5 years of disease were compared to 403 SSc patients who ever had a history of cancer. Antibodies against hPOP1, RPP25, RPP30, and RPP40 were assayed by immunoprecipitation of
Of 804 patients, 67 (8.3%) had antibodies against any component of the Th/To complex. Patients with antibodies to any component were significantly more likely to have limited cutaneous disease, less likely to have tendon friction rubs, and more likely to have findings consistent with interstitial lung disease or pulmonary hypertension. Patients with antibodies against hPOP1, RPP25, RPP30, and/or RPP40 were significantly less likely to develop cancer within 2 years of SSc onset (0% versus 11% of antibody-negative patients; P = 0.009). | SSc patients who produce autoantibodies to components of the Th/To complex have a clinical phenotype characterized by limited cutaneous disease and pulmonary involvement. Our findings show that the presence of any Th/To autoantibody may have a protective effect against contemporaneous cancer. |
3,505 | 37,241 | In the United Kingdom, organizations involved in health-care commissioning have recently introduced legislation limiting access to total knee arthroplasty through the introduction of arbitrary thresholds unsupported by the literature and based on body mass index. This study aimed to establish the relationship between body mass index and patient-reported specific and general outcomes on total knee arthroplasty.
Using national patient-reported outcome measures (PROMs) linked to the National Joint Registry, we identified 13,673 primary total knee arthroplasties performed for the treatment of osteoarthritis. The PROMs project involves the collection of condition-specific and general health outcomes before and at six months following total knee arthroplasty. The relationships between body mass index and the Oxford Knee Score, EuroQol 5D index, and EuroQol 5D Visual Analogue Scale were assessed with use of scatterplots and linear regression. The improvement in these measures was compared for three distinct groups based on body mass index (Group I [15 to 24.9 kg/m(2)], Group II [25 to 39.9 kg/m(2)], and Group III [40 to 60 kg/m(2)]) with use of multiple regression analysis to adjust for differences in age, sex, American Society of Anesthesiologists grade, general health rating, and number of comorbidities.
The preoperative and postoperative patient-reported outcome measures declined to a similar extent with increasing body mass index. The gradient of the linear regression equation relating to the change in scores was positive in all cases, indicating that there was a tendency for scores to improve to a greater extent as body mass index increased. After adjustment, the changes in patient-reported outcome measures in Group I and Group III were equivalent for the Oxford Knee Score (mean difference, 0.5 point [95% confidence interval, -0.5 to 1.5 points]; p = 0.78), the EuroQol 5D index (mean difference, 0.014 point [95% confidence interval, -0.021 to 0.048 point]; p = 1.00), and the EuroQol 5D Visual Analogue Scale (mean difference, 1.9 points [95% confidence interval, -0.4 to 4.1 points]; p = 0.13). Wound complications were significantly higher (p < 0.001) at a rate of 17% (168 of 1018 patients) in Group III compared with 9% (121 of 1292 patients) in Group I. | The improvements in patient-reported outcome measures experienced by patients were similar, irrespective of body mass index. Health policy should be based on the overall improvements in function and general health gained through surgery. Obese patients should not be excluded from the benefit of total knee arthroplasty, given that their overall improvements were equivalent to those of patients with a lower body mass index. |
3,506 | 22,796 | To assess the effect of allopurinol use on the risk of incident atrial fibrillation (AF) in the elderly.
We used the 5% random Medicare Claims data from 2006 to 2012 to examine the association of allopurinol use and incident AF in a cohort of patients with an absence of AF at baseline (at least 365 days). Multivariable-adjusted Cox regression analyses compared allopurinol exposed and non-exposed periods for the risk of AF, controlling for age, sex, race, Charlson-Romano comorbidity index and use of statins, diuretics, ACE inhibitors and β-blockers. HR with 95% CIs was calculated. Sensitivity analyses considered a longer baseline period (365 days vs 183 days) and individual comorbidities.
There were 9244 episodes of incident allopurinol use in 8569 beneficiaries, of which 1366 episodes (14.8%) had incident AF. In multivariable-adjusted analyses, allopurinol use was associated with an HR of 0.83 (95% CI 0.74 to 0.93) for incident AF. In a separate multivariable-adjusted model, compared with no allopurinol use, longer allopurinol use durations were associated with a lower HR of AF: 180 days-2 years, 0.85 (95% CI 0.73 to 0.99) and >2 years, 0.65 (95% CI 0.52 to 0.82). Other factors significantly associated with a higher hazard of AF were: age 75-<85 years and ≥85 years, higher Charlson index score and current β-blocker use. Sensitivity analyses confirmed these findings with minimal/no attenuation of HRs. | Allopurinol use was associated with a reduced risk of incident AF in the elderly, especially its use for >6 months duration. Future studies should assess the mechanisms underlying this beneficial effect of allopurinol. |
3,507 | 27,024 | We evaluated the safety of current treatment regimens for patients with RA and HBV in a large US cohort.
We identified biologic and nonbiologic treatment episodes of RA patients using 1997 to 2011 national data from the US Veterans Health Administration. Eligible episodes had evidence of HBV infection (HBV surface antigen, HBV core antibody, HBV e-antibody and/or HBV DNA) and had a baseline alanine aminotransferase (ALT) <1.5 times the upper limit of laboratory normal within 90 days prior to initiation of a new biologic or nonbiologic DMARD. The main outcome of interest was hepatotoxicity, defined as ALT elevation >100 IU/mL. Results were reported as the cumulative incidence of treatment episodes achieving hepatotoxicity at 3, 6 and 12 months post biologic exposure.
Five hundred sixty-six unique RA patients with HBV contributed 959 treatment episodes. Mean age was 62.1 ± 10.3 years; 91.8% were male. Hepatotoxicity was uncommon, with 26 events identified among 959 episodes (2.7%) within 12 months. Hepatotoxicity was comparable between biologic and nonbiologic DMARDs (2.6% vs. 2.8%, P = 0.87). The median time between HBV screening and starting a new RA drug was 504 days (IQR 144, 1,163). Follow-up HBV testing occurred among 14 hepatotoxicity episodes (53.8%) at a median of 202 days (IQR 82, 716) from the date of ALT elevation. A total of 146 (15.2%) treatment episodes received at least one test for HBV DNA at any point in the observation period. | Among US veterans with RA and HBV the risk of hepatotoxicity is low (2.7%), and comparable between biologic and nonbiologic DMARDS (2.8% vs. 2.6%, P = 0.87). HBV testing associated with DMARD initiation or hepatotoxicity was infrequent. |
3,508 | 8,197 | The aim of this study is to evaluate the efficacy of genicular nerve block (GNB) and intraarticular corticosteroid injection (IACSI) in patients with knee osteoarthritis (OA).
Forty patients with Kellgren-Lawrence grade 2-4 knee OA were included for the study. Patients were divided into two groups randomly as IACS and IACS + GNB groups. All patients were evaluated with ultrasound for cartilage thickness, patellar tendon thickness, quadriceps tendon thickness and quadriceps muscle cross-sectional area (QMA). Pain intensity of the patients was evaluated with visual analogue scale and the Leeds Assessment of Neuropathic Symptoms and Signs pain scale. Functional status of the patients was evaluated with Western Ontario and Mc Master Universities Osteoarthritis Index. Quality of life of the patients was assessed with Nottingham Health Profile (NHP). All assessments were measured and compared at baseline, 1st month and 3rd month after treatment.
All evaluation parameters were significantly improved in IACSI and IACSI + GNB groups. However, the improvement was better in IACSI + GNB group compared to those in IACSI group in terms of all evaluation parameters except QMA (0.10 ± 0.18 and 0.11 ± 0.22, respectively) and NHP scores in 1st month evaluation (- 3.11 ± 6.99 and - 3.54 ± 1.74, respectively). | When combined with IACSI, GNB yields better analgesic effect and improves function in patients with knee OA compared to only IACSI. |
3,509 | 12,536 | To investigate the impact of body mass index (BMI) on clinical disease activity indices and clinical and sonographic remission rates in patients with rheumatoid arthritis (RA).
Sixty-three patients with RA were categorized according to BMI score into three groups: normal (BMI<25), overweight (BMI 25-30) and obese (BMI≥30). Thirty-three of them were treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), and 30 with biologic DMARDs (bDMARDs). Patients underwent clinical and laboratory assessment and musculoskeletal ultrasound examination (MSUS) at baseline and at 6 months after initiation of therapy. We evaluated the rate of clinical and sonographic remission (defined as Power Doppler score (PD) = 0) and its correlation with BMI score.
In the csDMARDs group, 60% of the normal weight patients reached DAS28 remission; 33.3% of the overweight; and 0% of the obese patients. In the bDMARDs group, the percentage of remission was as follows: 60% in the normal weight subgroup, 33.3% in the overweight; and 15.8% in the obese. Within the csDMARDs treatment group, two significant correlations were found: BMI score-DAS 28 at 6th month, rs = .372, p = .033; BMI score-DAS 28 categories, rs = .447, p = .014. Within the bDMARDs group, three significant correlations were identified: BMI score-PDUS at sixth month, rs = .506, p =.004; BMI score-DAS 28, rs = .511, p = .004; BMI score-DAS 28 categories, rs = .592, p = .001. Sonographic remission rates at 6 months were significantly higher in the normal BMI category in both treatment groups. | BMI influences the treatment response, clinical disease activity indices and the rates of clinical and sonographic remission in patients with RA. Obesity and overweight are associated with lower remission rates regardless of the type of treatment. |
3,510 | 39,544 | To evaluate the efficacy of topical nonsteroidal anti-inflammatory drugs (NSAID) to relieve temporomandibular joint (TMJ) degenerative joint disease (DJD) pain.
A search of the literature was made using electronic databases complemented with a manual search. Clinical trials comparing topical NSAID with either placebo or an alternative active treatment to treat TMJ DJD pain were identified. Outcomes evaluated were pain reduction/pain control and/or incidence of side effects.
A single study (double-blind randomized placebo-controlled trial) with 20 patients was identified that evaluated the efficacy of a topically prepared NSAID over a 12-week duration, measuring functional pain intensity, voluntary and assisted mouth opening, pain disability index, and a brief pain inventory analysis. This study revealed a pain intensity decrease within treatment groups but no significant difference between treatment groups. | Presently, there is insufficient evidence to support the use of topically applied NSAID medications to palliate TMJ DJD pain. |
3,511 | 23,770 | Patients with resolved hepatitis B virus (HBV) infection, i.e., hepatitis B surface antigen (HBsAg)-negative/antihepatitis B core antigen (anti-HBc)-positive, undergoing rituximab (RTX)-based chemotherapy for hematological malignancies without anti-HBV prophylaxis are at risk of HBV reactivation, but the risk in such patients receiving RTX for rheumatological disorders is not clear. We evaluated this risk in HBsAg-negative/anti-HBc-positive patients with rheumatoid arthritis (RA) undergoing RTX without prophylaxis.
Thirty-three HBsAg-negative/anti-HBc-positive outpatients with RA with undetectable HBV DNA by sensitive PCR assay [73% women, median age 60 years, 85% with HBsAg antibodies (anti-HBs), 37% with antihepatitis B envelope antigen] received a median of 3 cycles of RTX (range 1-8) over 34 months (range 0-80) combined with disease-modifying antirheumatic drugs (DMARD) without prophylaxis. All underwent clinical and laboratory monitoring during and after RTX administration, including serum HBsAg and HBV DNA measurements every 6 months or whenever clinically indicated.
None of the patients seroreverted to HBsAg during RTX treatment, but 6/28 (21%) showed a > 50% decrease in protective anti-HBs levels, including 2 who became anti-HBs-negative. One patient (3%) who became HBV DNA-positive (44 IU/ml) after 6 months of RTX treatment was effectively rescued with lamivudine before any hepatitis flare occurred. Among the 14 patients monitored for 18 months (range 0-70) after RTX discontinuation, no HBV reactivation was observed. | The administration of RTX + DMARD in patients with RA with resolved HBV infection leads to a negligible risk of HBV reactivation, thus suggesting that serum HBsAg and/or HBV DNA monitoring but not universal anti-HBV prophylaxis is justified. |
3,512 | 33,071 | To identify inefficiencies in drug and medical service utilization related to pain management in patients with osteoarthritis and chronic low back pain.
This retrospective cohort study applied revised measures of pain management inefficiencies to Humana Medicare members with osteoarthritis and/or chronic low back pain.
Subjects had either 2 or more claims for osteoarthritis on different days or 2 or more claims for low back pain 90 or more days apart, from January 1, 2008, to June 30, 2010, with the first occurrence assigned the index date. Inefficiencies were identified for 365 days postindex.Pain-related healthcare costs postindex were compared between members with and without inefficiencies. A generalized linear model calculated adjusted costs per member controlling for age, sex, and comorbidities.
Most members diagnosed with osteoarthritis, chronic low back pain, or both (N = 68,453) had at least 1 inefficiency measure (n = 37,863) during the postindex period. High per member costs were for repeated surgical procedures ($26,451) and inpatient admissions ($19,372) compared with members without inefficiencies ($781; P < .0001). High total costs (prevalence times per member cost) were for repeated diagnostic testing and excessive office visits. Members with an inefficiency had adjusted pain-related costs 5.42 times higher than those of members without an inefficiency (P <.0001). | Pain management inefficiencies are common and costly among Humana Medicare members with osteoarthritis and/or chronic low back pain. Further work by providers and payers is needed to determine benefits of member identification and early intervention for these inefficiencies. |
3,513 | 65,314 | We investigated the effects of intraarticularly applied hyaluronic acid on the cartilage-integrity with early-forms of retropatellar cartilage degeneration (chondromalacia patellae) in dogs.
We used the Pond-Nuki model (tenotomy and resection of the anterior cruciate ligament = ACL) in 27 dogs (foxhounds) (3 groups of 9 animals) PILOT STUDY: ACL-tenotomy and resection, no therapy, specimens retrieval after 3, 6, 12 weeks (3 animals each period). VERUM: ACL-tenotomy and resection, hyaluronic acid (start after 3, 6, 12 weeks), 5 injections in 4 weeks, specimens retrieval after 5 weeks following final injection (12, 15, 21 weeks postoperatively, 3 dogs each period). PLACEBO: same procedure as verum, but saline-injections. Specimens were taken from the medial/lateral patellar pole from both, the operated and the normal knee and examined histologically using various staining methods (HE, Azan, Toluidin, Masson-Goldner, Safranin-O). A modified Mankin score was used to grade cartilage degeneration.
Our results demonstrate that the Pond-Nuki model is suitable to experimentally induce chondromalacia patellae. There were significantly less degenerative cartilage changes in the knees treated with hyaluronic acid compared to the placebo-group. | Our results let assume that hyaluronic acid could be indicated i.e. after arthroscopically diagnosed early cartilage-degeneration, the final conclusions concerning the actual mechanisms and therapeutical effectiveness need however further prospective clinical and experimental investigations. |
3,514 | 761 | To investigate whether thermogenesis and the hypothalamus may be involved in the physiopathology of experimental arthritis (EA).
EA was induced in male Lewis rats by intradermal injection of Freund's complete adjuvant (CFA). Food intake, body weight, plasma cytokines, thermographic analysis, gene and protein expression of thermogenic markers in brown adipose tissue (BAT) and white adipose tissue (WAT), and hypothalamic AMP-activated protein kinase (AMPK) were analyzed. Virogenetic activation of hypothalamic AMPK was performed.
We first demonstrated that EA was associated with increased BAT thermogenesis and browning of subcutaneous WAT leading to elevated energy expenditure. Moreover, rats experiencing EA showed inhibition of hypothalamic AMPK, a canonical energy sensor modulating energy homeostasis at the central level. Notably, specific genetic activation of AMPK in the ventromedial nucleus of the hypothalamus (a key site modulating energy metabolism) reversed the effect of EA on energy balance, brown fat, and browning, as well as promoting amelioration of synovial inflammation in experimental arthritis. | Overall, these data indicate that EA promotes a central catabolic state that can be targeted and reversed by the activation of hypothalamic AMPK. This might provide new therapeutic alternatives to treat rheumatoid arthritis (RA)-associated metabolic comorbidities, improving the overall prognosis in patients with RA. |
3,515 | 65,876 | This study was conducted to measure the intra-articular levels of prostaglandin E2 (PGE2), hyaluronic acid, and chondroitin-4 and -6 sulfate in patients with temporomandibular joint (TMJ) internal derangement involving a closed lock, and to see if these levels correlate with the clinical or arthroscopic findings.
Fifteen female patients (16 joints) with a mean age of 36.7 years were diagnosed as having a closed lock by clinical examination and diagnostic MR imaging. The patient's subjective pain was assessed by a visual analog scale (VAS) and a pain questionnaire (pain score), and the interincisal opening was measured. TMJ aspirates were obtained by washing of the joint with saline containing vitamin B12 as a marker for calibration of data. The samples were assayed for PGE2 with a radioimmunoassay, and the concentrations of unsaturated disaccaride isomers of hyaluronic acid (delta di-HA), chondroitin-4 sulfate (delta di-4S), and chondroitin-6 sulfate (delta di-6S) were measured by high-performance liquid chromatography. Immediately after collection of the synovial aspirates, diagnostic arthroscopy was performed on all but three joints to evaluate the severity of synovitis and cartilage degeneration. The degree of arthroscopic pathology was scored quantitatively. Intra-articular levels of PGE2, delta di-HA(HA), delta di-4S(C4S), and delta di-6S(C6S) were compared with patient's age, mouth opening, VAS rating, pain scores, and arthroscopic scores for synovitis and cartilage degeneration.
The PGE2 level did not correlate with the clinical or arthroscopic parameters. HA had a weak correlation with mouth opening (0.54). C4S and C6S were correlated with arthroscopic scores of TMJ degeneration (0.97, 0.89) and with age (0.75, 0.62). The ratio of C4S and C6S to HA was also correlated with the arthroscopic indices of degeneration (0.93, 0.8) and PGE2 level (0.74, 0.69), but not with age. | The PGE2 level in the TMJ synovial fluid does not specifically reflect the intensity of pain or synovitis, but the detection of high concentrations of C4S and C6S, compared with the amount of HA, is a possible marker of proteoglycan degradation in the TMJ. |
3,516 | 10,932 | Cyclic phosphatidic acid (cPA) has an inhibitory effect on the autotaxin (ATX)/lysophosphatidic acid (LPA) axis, which has been implicated to play an important role in the progression of fibrosis in systemic sclerosis (SSc). The purpose of this study is to assess the antifibrotic activity of cPA for the treatment of SSc using SSc skin fibroblasts and an animal model of bleomycin-induced skin fibrosis.
We used a chemically stable derivative of cPA (2ccPA). First, we investigated the effect of 2ccPA on extracellular matrix (ECM) expression in skin fibroblasts. Next, the effect of 2ccPA on the intracellular cAMP levels was determined to investigate the mechanisms of the antifibrotic activity of 2ccPA. Finally, we administered 2ccPA to bleomycin-induced SSc model mice to evaluate whether 2ccPA prevented the progression of skin fibrosis.
2ccPA decreased ECM expression in SSc skin fibroblasts and TGF-β1-treated healthy skin fibroblasts without LPA stimulation. 2ccPA increased the intracellular cAMP levels in skin fibroblasts, suggesting that the antifibrotic effect of 2ccPA was the consequence of the increase in the intracellular cAMP levels. Administration of 2ccPA also ameliorated the progression of bleomycin-induced skin fibrosis in mice. | Our data indicated that 2ccPA had inhibitory effects on the progression of skin fibrosis by abrogating ECM production from activated skin fibroblasts. These cells were repressed, at least in part, by increased intracellular cAMP levels. 2ccPA may be able to be used to treat fibrotic lesions in SSc. |
3,517 | 47,359 | The pathophysiology underlying methotrexate (MTX)-induced pneumonitis has been considered as a hypersensitive reaction. The lymphocyte transformation test (LTT) is frequently used to detect hypersensitivity. Whereas previous reports have proposed that the LTT is not ideal to detect hypersensitivity to MTX, it has not been directly confirmed.
Forty rheumatoid arthritis (RA) patients (24 patients currently taking MTX and 16 patients with a past history of MTX administration) and 13 healthy subjects were recruited. LTT with MTX was used to assess thymidine incorporation. An MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay was also performed. The mitogenic activity was expressed as the Stimulatory Index (SI). The activity of RA was assessed by the disease activity score 28 (DAS28).
In the presence of MTX, the SI measured by the LTT and by the MTS assay showed an inverse correlation. The presence of MTX significantly elevated the SI values measured by the LTT. However, the SI values were significantly lower in RA patients currently taking MTX than those of patients not currently taking MTX, although DAS28 was not different. Furthermore, a past history of MTX-induced pneumonitis did not affect the SI values. | LTT with MTX in RA patients is not appropriate to detect MTX-induced pneumonitis. |
3,518 | 26,767 | The goal of the Outcome Measures in Rheumatology (OMERACT) 12 (2014) equity working group was to determine whether and how comprehensibility of patient-reported outcome measures (PROM) should be assessed, to ensure suitability for people with low literacy and differing cultures.
The English, Dutch, French, and Turkish Health Assessment Questionnaires and English and French Osteoarthritis Knee and Hip Quality of Life questionnaires were evaluated by applying 3 readability formulas: Flesch Reading Ease, Flesch-Kincaid grade level, and Simple Measure of Gobbledygook; and a new tool, the Evaluative Linguistic Framework for Questionnaires, developed to assess text quality of questionnaires. We also considered a study assessing cross-cultural adaptation with/without back-translation and/or expert committee. The results of this preconference work were presented to the equity working group participants to gain their perspectives on the importance of comprehensibility and cross-cultural adaptation for PROM.
Thirty-one OMERACT delegates attended the equity session. Twenty-six participants agreed that PROM should be assessed for comprehensibility and for use of suitable methods (4 abstained, 1 no). Twenty-two participants agreed that cultural equivalency of PROM should be assessed and suitable methods used (7 abstained, 2 no). Special interest group participants identified challenges with cross-cultural adaptation including resources required, and suggested patient involvement for improving translation and adaptation. | Future work will include consensus exercises on what methods are required to ensure PROM are appropriate for people with low literacy and different cultures. |
3,519 | 64,857 | To describe the way in which the fibromyalgia patients understand the meaning of their illness.
Qualitative, empirical phenomenological psychological method.
A collaborative transdisciplinary interview study of patients' described experiences of living with fibromyalgia. No therapeutic relationships existed between patients and researchers.
Eighteen patients with fibromyalgia were interviewed. Ten of the 18 taped interviews were transcribed and analysed.
Patients' narratives, described experiences of living with fibromyalgia.
The patients were intensively involved in efforts to get their self-images as ill persons confirmed. Their experience was that the disease started dramatically, with a variety of capriciously appearing symptoms of unknown cause that gave rise to the suffering. The fibromyalgia patients seemed to develop strategies to cope with a precarious self-image and find ways to manage the thought of what the future would bring. | The meaning structures revealed in the patients' ways of describing their experiences of living with fibromyalgia seemed to be partially constituted by their efforts to stand forth as afflicted with a disease, which could be a way to help them to manage the demands that they placed upon themselves. |
3,520 | 23,657 | Indoleamine 2,3-dioxygenase-1 (IDO1) is an immune-modulatory enzyme that catalyzes the degradation of tryptophan (Trp) to kynurenine (Kyn) and is strongly induced by interferon (IFN)-γ. We previously reported highly increased levels of IFN-γ and corresponding IDO activity in patients with hemophagocytic lymphohistiocytosis (HLH), a hyper-inflammatory syndrome. On the other hand, IFN-γ and IDO were low in patients with systemic juvenile idiopathic arthritis (sJIA), an autoinflammatory syndrome. As HLH can occur as a complication of sJIA, the opposing levels of both IFN-γ and IDO are remarkable. In animal models for sJIA and HLH, the role of IFN-γ differs from being protective to pathogenic. In this study, we aimed to unravel the role of IDO1 in the pathogenesis of sJIA and HLH.
Wild-type and IDO1-knockout (IDO1-KO) mice were used in 3 models of sJIA or HLH: complete Freund's adjuvant (CFA)-injected mice developed an sJIA-like syndrome and secondary HLH (sHLH) was evoked by either repeated injection of unmethylated CpG oligonucleotide or by primary infection with mouse cytomegalovirus (MCMV). An anti-CD3-induced cytokine release syndrome was used as a non-sJIA/HLH control model.
No differences were found in clinical, laboratory and hematological features of sJIA/HLH between wild-type and IDO1-KO mice. As IDO modulates the immune response via induction of regulatory T cells and inhibition of T cell proliferation, we investigated both features in a T cell-triggered cytokine release syndrome. Again, no differences were observed in serum cytokine levels, percentages of regulatory T cells, nor of proliferating or apoptotic thymocytes and lymph node cells. | Our data demonstrate that IDO1 deficiency does not affect inflammation in sJIA, sHLH and a T cell-triggered cytokine release model. We hypothesize that other tryptophan-catabolizing enzymes like IDO2 and tryptophan 2,3-dioxygenase (TDO) might compensate for the lack of IDO1. |
3,521 | 59,100 | To characterize the expression pattern of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its cognate receptors (TRAIL R1, R2, R3, and R4) on rheumatoid arthritis (RA) synovial fluid (SF) lymphocytes and monocyte/macrophages and on cultured RA synovial fibroblasts.
The expression of TRAIL and TRAIL receptors on RA SF lymphocytes and monocyte/macrophages, normal macrophages, and RA synovial fibroblasts was examined by flow cytometry with previously characterized monoclonal antibodies. The ability of adenoviral-mediated delivery of TRAIL to induce macrophage or RA synovial fibroblast apoptosis was examined by flow cytometry.
By flow cytometry, neither TRAIL nor its cognate receptors was detectable on RA SF lymphocytes or RA synovial fibroblasts. In contrast, RA SF macrophages expressed TRAIL R3, a decoy receptor (P < 0.01 versus isotype control), but not TRAIL, or TRAIL R1, R2, or R4. Normal peripheral blood-derived monocyte-differentiated macrophages expressed TRAIL R2 (P < 0.01), but not TRAIL or the other TRAIL receptors. Adenoviral-mediated delivery of TRAIL had no effect on the survival of normal macrophages or RA synovial fibroblasts but readily induced apoptosis in the prostate cancer cell line (PC-3) that expressed TRAIL R1 and R2. | TRAIL R1 and R2, which are required for signal transmission by TRAIL, were not detected on RA SF lymphocytes, macrophages, or synovial fibroblasts. These observations do not support a potential therapeutic role for TRAIL in RA. |
3,522 | 4,516 | To determine whether changes in ultrasonography (US) features of monosodium urate crystal deposition is associated with the number of gouty flares after stopping gout flare prophylaxis.
We performed a 1-year multicentre prospective study including patients with proven gout and US features of gout. The first phase of the study was a 6-month US follow-up after starting urate-lowering therapy (ULT) with gout flare prophylaxis. After 6 months of ULT, gout flare prophylaxis was stopped, followed by a clinical follow-up (M6 to 12) and ULT was maintained. Outcomes were the proportion of relapsing patients between M6 and M12 according to changes of US features of gout and determining a threshold decrease in tophus size according to the probability of relapse.
We included 79 gouty patients [mean (±SD) age 61.8±14 years, 91% males, median disease duration 4 (IQR 1.5;10) years]. Among the 49 completers at M12, 23 (47%) experienced relapse. Decrease in tophus size ≥50% at M6 was more frequent without than with relapse (54% vs. 26%, P=0.049). On ROC curve analysis, a threshold decrease of 50.8% in tophus size had the best sensitivity/specificity ratio to predict relapse [AUC 0.649 (95% confidence interval 0.488; 0.809)]. Probability of relapse was increased for patients with a decrease in tophus size <50% between M0 and M6 [OR 3.35 (95% confidence interval 0.98; 11.44)]. | A high reduction in US tophus size is associated with lower probability of relapse after stopping gout prophylaxis. US follow-up may be useful for managing ULT and gout flare prophylaxis. |
3,523 | 45,558 | To study the regulatory effect of fengshiqing (FSQ) on interleukin 4 (IL-4), gamma-interferon (gamma-IFN), macrophage inflammatory protein 1alpha (MIP-1alpha) and collagen type II antibody (C II Ab) in serum and supernatant of synovial cell culture of rat with rheumatoid arthritis (RA), to explore the mechanism of action of clearing-heat and activating blood method for treatment of RA.
RA rat model was induced by C II Ab combined with Freund's complete adjuvant, and the levels of IL-4, gamma-IFN, MIP-1alpha and C II Ab in serum and supernatant of synovial cell were detected by ELISA.
As compared with the normal group, serum level of C II Ab in the model group was significantly higher (P < 0.01), serum and supernatant contents of IL-4 on the 14th and 28th day of modeling were lower and those of gamma-IFN and MIP-1alpha were higher, the difference showed statistical significance (P < 0.05 or P < 0.01). After being treated with FSQ and IL-4 contents in serum and supernatant as well as MIP-1alpha in supernatant restored on the 14th day (P < 0.05 or P < 0.01), while all the indexes restored on the 28th day. | FSQ could evidently up-regulate the level of IL-4 and down-regulate that of MIP-1alpha in serum and local synovial membrane in RA rats, and shows a suppressive trend of gamma-IFN, so as to maintain the Th1/Th2 equilibrium, suppress the cellular and humoral immune response in the local synovial membrane, and alleviate the chronic changes of arthritis, synovitis and vasculitis. |
3,524 | 53,921 | To quantify the urinary concentration of cartilage oligomeric matrix protein (COMP), and to evaluate the relationship between urinary COMP concentration and the catabolic activity of synovial fluid (SF) in diseased horses.
COMP in horse urine was detected by immunoblotting with a monoclonal antibody (mAb; 14G4) raised against equine COMP from articular cartilage. Urine and serum samples were obtained from 83 Thoroughbred horses with aseptic joint diseases (AJD, 79 horses) or septic joint diseases (SJD, four horses) at the time of anesthesia induction, and samples of SF were obtained during surgery. Control samples of urine (n=111) were collected from normal horses free of any orthopedic diseases after they had been racing. COMP concentration was determined in all samples using inhibition enzyme-linked immunosorbent assay (ELISA) with mAb 14G4. SF samples were also used for the quantification of gelatinase activity.
Positive bands of COMP fragments were determined on the immunoblots with mAb 14G4. The urinary COMP concentrations in AJD and SJD horses (1.02+/-0.75 and 1.55+/-1.17 microg/100mg creatinine, respectively) were significantly higher than normal (0.57+/-0.29 microg/100mg creatinine). In 55 horses with fractures in the AJD group there was a logarithmic relationship (r=-0.45, P<0.001) between the urinary and SF COMP measurements, while the urinary COMP level was positively correlated with matrix metalloproteinase (MMP)-2 and -9 activities (r=0.30, P<0.05 and r=0.51, P<0.001, respectively) in SF. | The urinary COMP assay with mAb 14G4 is useful for discriminating horses with osteoarthritis. The higher COMP levels in urine from such horses would be indicative of enhanced proteolytic activity, in addition to the increased COMP levels in the diseased joints. |
3,525 | 61,946 | To explore the perceptions of multidisciplinary health care professionals (HCPs) and patients of the pharmaceutical care issues (PCIs) relating to rheumatoid arthritis (RA).
Qualitative study using semi-structured one to one interviews and focus groups to explore patient perceptions. Interviews and focus groups were taped and transcribed verbatim, then described and coded for meaning to produce 'in-vivo' codes, which were then grouped to form themes. Nominal group methodology was used to generate and rank a list of HCP perceptions of the key PCIs of RA patients. The PCIs were ranked according to clinical importance and order of occurrence from admission as perceived by the HCP group.
Rheumatology ward and outpatient clinic in a teaching hospital.
Generation and ranking of PCIs, generation of themes from patient interviews.
Optimisation of pain control was identified by the nominal group as being the primary aim for patients on admission and was also the most commonly described symptom by patients. Two PCIs not predicted by the HCPs' nominal group was the frequency of infections and the associated discharge and patients described experiencing 'over-education' by HCPs, which could lead to anxiety. Complementary medicine in conjunction with traditional therapy was raised as a significant health benefit by patients. | Many patients' views mirrored the PCIs identified by HCPs, but some were not anticipated; the value of patient interviews to ensure appropriate service development was demonstrated. Several PCIs emerged for future incorporation by the multi-disciplinary team into standardised models of pharmaceutical care for use in secondary care and at the secondary/primary care interface for improvement of seamless care. There is a need to target educational interventions and to identify those who will benefit from advice on complementary medicine. Further work is required to develop a tool to identify the educational needs of RA patients and targeting of the information provided. This will help ensure the delivery of pharmaceutical care is designed to match the needs of individual patients. |
3,526 | 14,235 | We aimed to assess risk factors for the development of severe infection in patients with antineutrophil cytoplasm antibody-associated vasculitis (AAV) receiving rituximab.
192 patients with AAV were identified. Univariate and multivariate analyses were performed to identify risk factors for severe infection following rituximab. Severe infections were classified as grade ≥3 as proposed by the Common Terminology Criteria for Adverse Events V.4.0.
95 severe infections were recorded in 49 (25.52%) patients, corresponding to an event rate of 26.06 per 100 person-years. The prophylactic use of trimethoprim-sulfamethoxazole was associated with a lower frequency of severe infections (HR 0.30, 95% CI 0.13 to 0.69), while older age (HR 1.03, 95% CI 1.01 to 1.05), endobronchial involvement (HR 2.21, 95% CI 1.14 to 4.26), presence of chronic obstructive pulmonary disease (HR 6.30, 95% CI 1.08 to 36.75) and previous alemtuzumab use (HR 3.97, 95% CI 1.50 to 10.54) increased the risk. When analysis was restricted to respiratory tract infections (66.3% of all infections), endobronchial involvement (HR 4.27, 95% CI 1.81 to 10.06), severe bronchiectasis (HR 6.14, 95% CI 1.18 to 31.91), higher neutrophil count (HR 1.19, 95% CI 1.06 to 1.33) and major relapse (HR 3.07, 95% CI 1.30 to 7.23) as indication for rituximab use conferred a higher risk, while refractory disease (HR 0.25, 95% CI 0.07 to 0.90) as indication had a lower frequency of severe infections. | We found severe infections in one quarter of patients with AAV receiving rituximab. Trimethoprim-sulfamethoxazole prophylaxis reduced the risk, while especially bronchiectasis and endobronchial involvement are risk factors for severe respiratory infections. |
3,527 | 37,064 | Fibromyalgia (FM) is a condition characterized by widespread pain and is estimated to affect 0.5-5% of the general population. Historically, it has been classified as a rheumatologic disorder, but patients consult physicians from a variety of specialties in seeking diagnosis and ultimately treatment. Patients report considerable delay in receiving a diagnosis after initial presentation, suggesting diagnosis and management of FM might be a challenge to physicians.
A questionnaire survey of 1622 physicians in six European countries, Mexico and South Korea was conducted. Specialties surveyed included primary care physicians (PCPs; n=809) and equal numbers of rheumatologists, neurologists, psychiatrists and pain specialists.
The sample included experienced doctors, with an expected clinical caseload for their specialty. Most (>80%) had seen a patient with FM in the last 2 years. Overall, 53% of physicians reported difficulty with diagnosing FM, 54% reported their training in FM was inadequate, and 32% considered themselves not knowledgeable about FM. Awareness of American College of Rheumatology classification criteria ranged from 32% for psychiatrists to 83% for rheumatologists. Sixty-four percent agreed patients found it difficult to communicate FM symptoms, and 79% said they needed to spend more time to identify FM. Thirty-eight percent were not confident in recognizing the symptoms of FM, and 48% were not confident in differentiating FM from conditions with similar symptoms. Thirty-seven percent were not confident developing an FM treatment plan, and 37% were not confident managing FM patients long-term. In general, rheumatologists reported least difficulties/greatest confidence, and PCPs and psychiatrists reported greatest difficulties/least confidence. | Diagnosis and managing FM is challenging for physicians, especially PCPs and psychiatrists, but other specialties, including rheumatologists, also express difficulties. Improved training in FM and initiatives to improve patient-doctor communication are needed and may help the management of this condition. |
3,528 | 23,922 | Methotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug (DMARD) in juvenile idiopathic arthritis (JIA). In Dutch patients, MTX intolerance occurred frequently and was associated with subcutaneous (SC) administration. The aim of this study was to assess the prevalence of MTX intolerance and its association with the route of administration in a German cohort of JIA patients.
A cross-sectional study of JIA patients on MTX was performed. Primary outcome was MTX intolerance, which was determined using the validated Methotrexate Intolerance Severity Score (MISS) questionnaire. The prevalence of gastrointestinal adverse effects and MTX intolerance was compared between patients on MTX SC and MTX administered orally (PO).
Of 179 JIA patients on MTX, 73 (40.8%) were intolerant. The odds of MTX intolerance were higher in patients using MTX exclusively SC compared to exclusively PO (adjusted odds ratio 3.37 [95% confidence interval 1.19-10.0]). There was strong evidence that the former experienced more behavioural complaints (76.1% vs. 47.4%, p=0.001) and weak evidence that they experienced more abdominal pain after MTX intake (43.5% vs. 27.4%, p=0.056). | The prevalence of MTX intolerance was high and exclusively SC administration of MTX was associated with MTX intolerance and behavioural adverse effects. The prevalence of gastrointestinal adverse effects was at least as high as in patients on MTX PO. The frequently held assumption that SC causes fewer side effects than PO seems unwarranted. Definite answers about the differences between SC and PO administration with respect to safety and efficacy should be obtained by randomised trials. |
3,529 | 33,557 | Hyperuricemia is associated with the presence and severity of obstructive sleep apnea (OSA). Previous work has shown that treatment of OSA with continuous positive airway pressure (CPAP) therapy reduces urinary uric acid excretion and serum urate, but there has been no previous randomized controlled investigation on the effects of CPAP therapy on serum urate; we aimed to assess this association.
Serum urate was measured in samples from participants of a previously published randomized controlled trial. Samples were taken at baseline and after 3months from men with known type 2 diabetes mellitus (T2DM) and newly diagnosed OSA, randomized to receive either therapeutic (n=19) or placebo (n=19) CPAP for 3months.
Both groups were well matched at baseline, with no significant difference in age, body mass index (BMI), glycosylated hemoglobin (HbA1c), or oxygen desaturation index (ODI). There was no significant difference in therapeutic or placebo CPAP usage. There was no significant difference in urate levels between groups at baseline (362μmol/L [standard deviation {SD}, 96] vs 413μmol/L [SD, 91] [reference range, 110-428μmol/L]) or at 3months. Baseline urate did not correlate with ODI, BMI, or HbA1c. The mean change in urate at 3months did not significantly differ between treatment groups (-7.6μmol/L [SD, 35.9] vs -6.2μmol/L [SD, 46.2]) (P=.9; [95% confidence interval, -28.7 to +25.9]). | Our randomized controlled trial has shown no significant reduction in serum urate following 3months treatment with therapeutic or placebo CPAP. |
3,530 | 38,744 | The purpose of this study was to compare the clinical and radiographic outcomes of opening- and closing-wedge valgus high tibial osteotomy (HTO) for the treatment of medial unicompartmental knee osteoarthritis with a minimum follow-up of 3 years, with a focus on patellofemoral alignment and anterior knee pain.
We performed a retrospective comparison of 50 patients who underwent closing-wedge HTO and 50 patients who underwent opening-wedge HTO for isolated medial joint arthritis of the knee with varus deformity. All patients were evaluated and the 2 study groups were compared after a minimum follow-up of 3 years with a focus on patellofemoral alignment, patellofemoral osteoarthritis, and anterior knee pain while climbing stairs.
Patellar alignment (patellar tilt and lateral patellar displacement) was not significantly different in the 2 groups either preoperatively or at follow-up. Furthermore, there were no significant differences in the extent of patellofemoral arthritis and incidence of anterior knee pain at follow-up between the 2 groups. In addition, no significant intergroup difference was found in terms of the incidence of anterior knee pain (28% in closing-wedge group and 32% in opening-wedge group at follow-up).
Level III, retrospective comparative study. | The results of closing- and opening-wedge valgus HTO were not found to be significantly different with respect to patellar alignment, osteoarthritis of the patellofemoral joint, or anterior knee pain. |
3,531 | 15,578 | To explore the variables associated with initial favorable power Doppler (PD) ultrasound (US) response induced by biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in patients with rheumatoid arthritis (RA).
We have been prospectively investigating the course of active RA patients using US after the introduction of b/tsDMARDs in the Kyushu region of Japan since June 2013. A total of 150 patients have completed the first 6 months of observation at present and have been evaluated. US was assessed in 22 joints of bilateral hands using gray-scale and PD images on a scale from 0-3. The sum of these scores was used as the indicator of US disease activity. We defined PD remission as attaining a total PD score of 0 at 6 months and investigated the associated variables by multivariate logistic regression analysis.
The total PD and gray-scale scores and the clinical composite measures significantly improved at 6 months, whereas these reductions were less in bDMARD switchers as compared with bDMARD-naive patients. Multivariate logistic regression analysis showed that short disease duration, the absence of any previous use of bDMARDs, and low total PD scores at baseline were independent predictors of PD remission at 6 months. | This present prospective US cohort has for the first time shown the variables that are associated with initial PD response to b/tsDMARDs. |
3,532 | 17,561 | This analysis evaluated whether osteoarthritis patients achieving the greatest pain control and lowest pain states also have the greatest improvement in functioning and quality of life.
Patients (n=419) who failed prior therapies and who were switched to etoricoxib 60mg were categorized as pain responders or non-responders at 4 weeks based on responder definitions established by the Initiative on Methods, Measurement, and Pain (IMMPACT) criteria, including changes from baseline of ≥15%, ≥30%, ≥50%, ≥70% and a final pain status of ≤3/10 (no worse than mild pain). Pain was assessed at baseline and 4 weeks using 4 questions from the Brief Pain Inventory (BPI) (worst pain, least pain, average pain, and pain right now), and also using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale. We examined the relationship between pain responses with changes from baseline in two functional measures (the BPI Pain Interference questions and the WOMAC Function Subscale) as well as changes from baseline in quality of life (assessed on the SF-36 Physical and Mental Component Summaries). We also sought to understand whether these relationships were influenced by the choice of the pain instrument used to assess response. We contrast the mean difference in improvements in the functional and quality of life instruments based on pain responder status (responder versus non-responder) and the associated 95% confidence limits around this difference.
Patients with better pain responses were much more likely to have improved functional responses and improved quality of life, with higher mean changes in these outcomes versus pain non-responders, regardless of the choice of IMMPACT pain response definition (e.g., using any of 15%, 30%, 50%, 70% change from baseline) or the final pain state of ≤3/10. There was an evident gradient, where higher levels of pain response were associated with greater mean improvements in function and quality of life. The finding that greater pain responses led to greater functional improvements and quality of life gains was not dependent on the manner in which pain was evaluated. Five different pain instruments (e.g., the 4 questions on pain from the BPI pain questionnaire and the WOMAC pain subscale) consistently demonstrated that pain responders had statistically significantly greater improvements in function and quality of life compared to pain non-responders. This suggests these results are likely to be generalizable to any validated pain measure for osteoarthritis.
Good pain improvements in osteoarthritis with a valid pain instrument are a proxy for good improvements in both function and quality of life. Therefore proper osteoarthritis pain assessment can lead to efficient evaluations in the clinic. | Pain is an efficient outcome measure for predicting broader patient response in osteoarthritis. Patients who do not achieve timely, acceptable pain states over 4 weeks were less likely to experience functional or quality of life improvements. |
3,533 | 15,955 | Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that affects different end organs, including skin and brain. We and others have previously shown the importance of macrophages in the pathogenesis of cutaneous and neuropsychiatric lupus. Additionally, autoantibodies produced by autoreactive B cells are thought to play a role in both the skin and central nervous system pathologies associated with SLE.
We used a novel inhibitor of Bruton's tyrosine kinase (BTK), BI-BTK-1, to target both macrophage and B cell function in the MRL-lpr/lpr murine model of SLE, and examined the effect of treatment on skin and brain disease.
We found that treatment with BI-BTK-1 significantly attenuated the lupus associated cutaneous and neuropsychiatric disease phenotypes in MRL/lpr mice. Specifically, BI-BTK-1 treated mice had fewer macroscopic and microscopic skin lesions, reduced cutaneous cellular infiltration, and diminished inflammatory cytokine expression compared to control mice. BTK inhibition also significantly improved cognitive function, and decreased accumulation of T cells, B cells, and macrophages within the central nervous system, specifically the choroid plexus. | Directed therapies may improve the response rate in lupus-driven target organ involvement, and decrease the dangerous side effects associated with global immunosuppression. Overall, our results suggest that inhibition of BTK may be a promising therapeutic option for cutaneous and neuropsychiatric disease associated with SLE. |
3,534 | 11,357 | We reviewed the associations between paraoxonase 1 (PON1) polymorphisms and susceptibility and PON1 activity in rheumatoid arthritis (RA) patients and compared PON1 activity between RA patients and controls.
We conducted a meta-analysis of PON1 Q192R and L55M polymorphism and RA risk data and determined the associations between PON1 Q192R polymorphism and PON1 activity in RA patients. We also compared serum/plasma PON1 activity levels in RA patients and controls.
Twelve studies were included in this meta-analysis. No association was observed between RA and the PON1 192R allele in any study subject (OR = 0.967, 95% CI = 0.829-1.129, p = 0.674). Analysis using recessive, dominant, or homozygous contrast models revealed no association between the PON1 192R allele and RA. Meta-analysis showed no association between RA and the PON1 55M allele (OR = 1.400, 95% CI = 0.738-2.658, p = 0.308). In the meta-analysis, PON1 activity was significantly higher in the RR genotype than in the QQ (SMD = 2.975, 95% CI = 2.157-3.792, p < 0.001) and QR (SMD = 1.265, 95% CI = 0.898-1.633, p < 0.001) genotypes. PON1 activity was significantly lower in the RA group than in the control group (SMD = - 3.176, 95% CI = - 5.070 to - 1.283, p < 0.001). | We found no association between the PON1 Q192R and L55M polymorphisms and susceptibility to RA, while PON1 Q192R polymorphism was associated with PON1 activity in RA patients; we found significantly lower PON1 activity in RA patients.Key points• PON1 Q192R polymorphism is associated with PON1 activity in RA patients..• PON1 activity is significantly lower in RA patients.. |
3,535 | 8,783 | To report the most up-to-date evidence on the effects of tumour necrosis factor (TNF)-alpha inhibition on cartilage with a focus on its clinical relevance.
A systematic review was performed by searching PubMed, Embase and Cochrane Library databases. Inclusion criteria were studies of any level of evidence published in peer-reviewed journals reporting clinical or preclinical results written in English. Relative data were extracted and critically analysed. PRISMA guidelines were applied, and risk of bias was assessed as well as the methodological quality of the included studies.
13 studies were included after applying the inclusion and exclusion criteria. Three were in vitro human studies from osteoarthritis (OA) patients. Ten were animal modal studies including two in vitro studies, and eight in vivo studies. TNF-alpha inhibition in in vitro studies was generally reported beneficial due to the improved osteochondral viability, proliferation and chondrogenesis. In addition, TNF-alpha inhibition was noted to be beneficial in promoting the natural repair of osteochondral lesions and has a chondroprotective effect in in vivo studies. | Based on current evidence, TNF might have the potential to interfere with the healing process of chondral and osteochondral defects occurring naturally or in low inflammatory environment after a cartilage repair procedure. Therefore, the use of biological agents to inhibit its action in cartilage repair surgery could be beneficial, and this could translate into a promising therapy that improves the outcome of currently available cartilage procedures. |
3,536 | 29,614 | Anticyclic citrullinated peptide antibodies (anti-CCP) are considered specific markers of rheumatoid arthritis (RA) and have been included in the revised classification criteria for RA diagnosis. However, these antibodies have also been detected in patients with other types of chronic inflammatory rheumatism. Our objectives were to identify the prevalence of positive anti-CCP patients in non-RA diseases, to determine the diagnostic value of anti-CCP for the diagnosis of RA, to specify the clinical characteristics of non-RA patients positive for anti-CCP, and to determine the discriminatory value of the levels of anti-CCP in patients among the various diseases.
We carried out an observational and descriptive study. All the determinations of anti-CCP requested by the 2 rheumatology departments at Cochin Hospital over a period of 18 months were analyzed. Such determinations were requested for 1162 patients in total. Anti-CCP levels were determined with the Euro Diagnostica ELISA kit, with values ≥ 25 U for this test being considered positive. The diagnosis of rheumatic conditions was the responsibility of the treating physician.
Anti-CCP antibodies were detected in 357 (30.7%) of the 1162 patients. The prevalence of anti-CCP was 292/417 (70.0%) in RA, 13/122 (10.6%) in patients with psoriatic arthritis, 13/62 (20.9%) in patients with unclassified rheumatism, 11/33 (33.3%) in patients with primary Sjögren syndrome, 5/30 (16.6%) in patients with systemic lupus erythematosus, 3/28 (10.7%) in patients with mixed connective tissue disorder, 3/36 (8.3%) in patients with systemic sclerosis, 7/44 (15.9%) in patients with juvenile arthritis, and 6/220 (2.7%) in patients with noninflammatory diseases. In the population of patients positive for anti-CCP, mean anti-CCP levels were 869.4 (± 978.4) U/ml, with no significant difference between RA [854.8 (± 959.8) U/ml] and any of the non-RA conditions [922.7 (± 1070.0) U/ml]. | Anti-CCP are a hallmark of RA, but may be observed in other inflammatory, systemic, or mechanical diseases. In this large cohort of patients, the presence of second-generation anti-CCP (anti-CCP2) antibodies is useful in diagnosing RA (70% sensitivity, 91.3% specificity), but examining the levels of these antibodies does not appear to offer further discriminatory power among patients who are anti-CCP2-positive. |
3,537 | 1,181 | To assess the safety, tolerability, pharmacokinetics, and efficacy of rituximab (RTX) in pediatric patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).
The Pediatric Polyangiitis Rituximab Study was a phase IIa, international, open-label, single-arm study. During the initial 6-month remission-induction phase, patients received intravenous infusions of RTX (375 mg/m
Twenty-five pediatric patients with new-onset or relapsing disease were enrolled at 11 centers (19 with GPA [76%] and 6 with MPA [24%]). The median age was 14 years (range 6-17 years). All patients completed the remission-induction phase. During the overall study period (≤4.5 years), patients received between 4 and 28 infusions of RTX. All patients experienced ≥1 adverse event (AE), mostly grade 1 or grade 2 primarily infusion-related reactions. Seven patients experienced 10 serious AEs, and 17 patients experienced 31 infection-related AEs. No deaths were reported. RTX clearance correlated with body surface area. The body surface area-adjusted RTX dosing regimen resulted in similar exposure in both pediatric and adult patients with GPA or MPA. Remission, according to the Pediatric Vasculitis Activity Score, was achieved in 56%, 92%, and 100% of patients by months 6, 12, and 18, respectively. | In pediatric patients with GPA or MPA, RTX is well tolerated and effective, with an overall safety profile comparable to that observed in adult patients with GPA or MPA who receive treatment with RTX. RTX is associated with a positive risk/benefit profile in pediatric patients with active GPA or MPA. |
3,538 | 53,451 | The primary goal of the Genetics of Generalized Osteoarthritis (GOGO) study is to identify chromosomal regions associated with increased susceptibility to generalized osteoarthritis (OA). Here we describe the study design and phenotype of the 2728 participants from the 1145 families recruited for this study.
GOGO is an investigator-initiated collaboration involving seven clinical academic sites and sponsored by GlaxoSmithKline. Family ascertainment was carried out between 1999 and 2002. A qualifying family required self-reported Caucasian ethnicity and at least two affected siblings with clinical hand OA. We hypothesized that this clinical phenotype would facilitate identification of participants with multijoint radiographic OA (rOA) in and beyond the hand. The "gold standard" case definition, however, was based on rOA (Kellgren-Lawrence grade > or =2) involving > or =3 hand joints distributed bilaterally and including at least one distal interphalangeal joint, with two of the three involved joints within a joint group (distal interphalangeal, proximal interphalangeal, or carpometacarpal). Radiographs of hips, knees and spine were also obtained. Additional siblings and living parents from qualifying families, both affected and unaffected, were invited to participate.
A total of 2706 participants had complete clinical and radiological examination data. Of these, 2569 participants met clinical examination criteria for affected status; while 1963 (73%) participants met the prespecified radiographic criteria for affected status. This corresponded to a total of 707 families with at least two affected siblings that met the hand rOA criteria. Of those individuals with rOA of the hand, the frequency of rOA at other sites was highest for the knee (51%) and spine (54%), and less common for the hip (25%). Concordance rates among hand affected siblings were greatest for spine (36%) followed by knee (31%) and hip (9%); a total of 53% of the affected sib pairs were concordant for specific patterns of generalized rOA involving the hand and large joints (knees, hips or spine). | GOGO represents a large multicenter collection of families with multiple joint OA that have been characterized both clinically and radiographically. The GOGO study will employ a comprehensive strategy for genetic screening based upon both qualitative and quantitative radiographic trait analyses, circulating biomarkers in a quantitative trait-based analysis, fine mapping, and candidate gene analysis. This sample should provide sufficient power to detect linkage to OA associated genes. |
3,539 | 41,799 | In this observational longitudinal study we estimate knee joint cartilage glycosaminoglycan (GAG) content, in patients with an acute anterior cruciate ligament (ACL) injury, with or without a concomitant meniscus injury.
29 knees (19 men/10 women) were prospectively examined by repeat delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), approximately 3 weeks and 2.3±1.3 (range 4.5) years after the injury. We estimated the GAG content (T1Gd) in the central weight-bearing parts of the medial and lateral femoral cartilage and compared results with a reference cohort (n=24) with normal knees and no history of injury examined by dGEMRIC at one occasion previously.
The healthy reference group had longer T1Gd values compared with the ACL-injured patients at follow-up both medially: 428±38 vs 363±61ms (P<0.0001) and laterally: 445±41 vs 396±48ms (P=0.0002). At follow-up T1Gd was lower in meniscectomized patients compared to those without a meniscectomy, both medially (-84ms, P=0.002) and laterally (-38ms, P=0.05). In the injured group, the medial femoral cartilage showed similar T1Gd at the two dGEMRIC investigations: 357±50 vs 363±61ms (P=0.57), whereas the lateral femoral cartilage T1Gd increased: 374±48 vs 396±48ms (P=0.04). | The general decrease in cartilage T1Gd in ACL-injured patients compared with references provide evidence for structural matrix GAG changes that seem more pronounced if a concomitant meniscal injury is present. The fact that post-traumatic OA commonly develops in ACL-injured patients, in particularly those with meniscectomy, suggests that shorter T1Gd may be an early biomarker for OA. |
3,540 | 50,022 | To develop and validate a disease-specific quality of life (QOL) measure for osteoarthritis (OA), the OAQoL, using the needs-based conceptual model.
In the first phase of this study, in-depth, semistructured interviews were conducted with 44 OA patients to explore the issues associated with impact of OA and to derive items for a draft OAQoL questionnaire. In phase 2, 17 OA patients were interviewed on the relevance, clarity, and ease of completion of the measure in structured interviews. In phase 3, the draft questionnaire was mailed to 635 patients to test the psychometric properties of the questionnaire using Rasch analysis. Test-retest assessment of the revised questionnaire was performed in phase 4 by mailing the questionnaire to an additional 201 participants, with a second questionnaire repeated 2 weeks later.
A 38-item draft measure was devised during phase 1 and mailed in phase 2. Rasch analysis of the draft questionnaire (n = 259) indicated initial misfit, which was rectified with the removal of 13 problematic items (chi(2)[75] = 83.602, P = 0.232). For the test-retest assessment (n = 60), 3 additional items were removed, leaving a 22-item OAQoL that demonstrated good fit to the Rasch model (chi(2)[44] = 44.559, P = 0.533) with excellent test-retest correlation (rho = 0.925, P < 0.001; z = -0.06, P = 0.995). | The OAQoL is a simple and easy to use 22-item unidimensional questionnaire developed specifically to assess the impact of OA on QOL. The measure has been developed as a true patient-based questionnaire and demonstrates good psychometric properties, including test-retest reliability. |
3,541 | 42,859 | The objective of this study was to compare ecological and recalled pain intensity assessments over 29 days in hip and knee osteoarthritis (O) and chronic low back pain (L).
Rheumatologists were asked to enroll patients with O and L, with pain intensity above 40 mm, in a prospective study for 29 days. Pain intensity was assessed with physicians on Days 1 and 29, and ecologically, over the intervening 28-day period, by random phone calls.
We carried out correlation analyses for 353 (159 O, 194 L) patients: Overall recalled daily pain was strongly correlated with calculated 3-day mean pain assessments (r=0.96 [O]; 0.93 [L]) and evening pain (r=0.96 [O], 0.90 [L]). Correlations between ecological and recalled measures were stronger for recall over the last 7 days than for recall over the last 28 days in osteoarthritis patients (r=0.78, r=0.63), but were similar for both recall periods in low back pain patients (r=0.70, r=0.72). Correlations between assessments for the last 7 and 28 days were stronger for ecological (r=0.88 [O], 0.91 [L]) than for clinical (r=0.77 [O]; 0.86 [L]) assessments. After adjustment for current pain intensity, correlations remained significant for ecological assessments, but not for clinical assessments. Recalled pain assessments were more accurate when made after 24 hours (r=0.71 [O]; 0.70 [L]) than when made after 48 hours (r=0.63 [O]; 0.61 [L]). | For both low back pain and osteoarthritis, overall daily pain recall is a reliable measurement correlated with daily ecological measurements, whereas a rapid decrease in recall occurs after 48 hours. The most reliable period for pain recall was 7 days, but the results obtained were influenced by current pain. |
3,542 | 56,777 | To investigate the effect of mechanical stress on finger osteoarthritis (OA) by comparing women from two occupations with different hand load but the same socio-economic grade, and to investigate whether hand load may affect the pattern of joint involvement in OA.
Radiographs of both hands of 295 dentists and 248 teachers were examined. Each interphalangeal (distal, proximal and thumb interphalangeal) and the metacarpophalangeal joints were graded (0 = no OA, 4 = severe OA) separately by using reference images. The co-involvement of different hand joints was analysed by logistic regression.
The distal interphalangeal joints were the most frequently involved joints. The non-dominant hand was more frequently affected by OA of grade 2 or more than the dominant hand. The prevalence of OA of grade 2 or more in any finger joint and also in any distal interphalangeal joint was higher among the teachers compared with the dentists (59 vs 48%, P = 0.020 and 58 vs 47%, P < 0.010 respectively). Finger OA showed more clustering in the ring and little fingers and more row clustering and symmetry in the teachers than in the dentists [age-adjusted odds ratio (OR) = 1.57, 95% confidence interval (CI) 1.10-2.23, OR = 1.84, 95% CI 1.28-2.64, and OR = 1.98, 95% CI 1.38-2.86 respectively]. The OR of more severe OA (grade 3 or more) in the right-hand thumb and the index and middle fingers was significantly elevated among the dentists compared with the teachers (OR 2.61, 95% CI 1.03-6.59). | Our findings indicate that finger OA in middle-aged women is highly prevalent and often polyarticular. Hand use may have a protective effect on finger joint OA, whereas continuing joint overload may lead to joint impairment. |
3,543 | 17,880 | To assess the intra- and inter-observer reliability of Ultrasound (US) in scoring B-mode, Doppler synovitis and combined B-mode and Doppler synovitis scores in different peripheral joints of Rheumatoid Arthritis (RA) patients.
Four rheumatologists with a formal training in Musculoskeletal US (MSKUS) particularly focus on definitions and scoring synovitis on B-mode and Doppler mode participated in a patient- based reliability exercise on 16 active RA patients. The four rheumatologists independently and consecutively performed a B-mode and Power Doppler (PD) US assessment of 7 joints of each patient in two rounds in a blinded fashion. Each joint was semi quantitatively scored from 0 to 3 for B-mode Synovitis (BS), Doppler Synovitis (DS), and combined B-mode/Doppler synovitis (CS). Intraobserver reliability was assessed by Cohen's κ. Interobserver reliability was assessed by unweight Light's κ.
The mean prevalence of synovitis on B-mode was 83% of joints; scores ranging from grade 1 in 18% of joints, to grade 3 in 33%. In 55% of joints synovial PD signal was detected and the distribution of scores range from 14% of joints for grade 3, to 26% for grade 2. After a total of 448 joints scanned with 896 adquired images our intraobserver and interobserver reliability was good to excellent for most of the joints. | Formal, structured and continuous training in musculoskeletal ultrasound would bring a good to excellent reproducibility in rheumatological hands with a high reliability in real time acquisition BS, DS and CS modalities for scoring synovitis in patients with active rheumatoid arthritis. |
3,544 | 12,935 | The aims of this study were to establish the likelihood of additional surgery after ankle fusion, determine the interval for developing osteoarthrosis in the ipsilateral subtalar or Chopart joints, and evaluate its clinical relevance.
A retrospective clinical and radiological study with a minimum follow-up of 24 months was performed. Short-Form 36 Heath Survey, Foot Function Index, American Orthopaedic Foot and Ankle Society Score (AOFAS) and a visual analog scale (VAS) were used to evaluate pain level and quality of life in at least 62 adult patients.
A total of 57% of our patients developed osteoarthrosis in at least one of the related joints and 28% of them required additional surgery due to pain. Patients who received workers' compensation had significantly lower AOFAS and higher VAS pain values. | More than half of the study cohort developed osteoarthrosis in the related joints after ankle fusion, but fewer than one-third required further joint fusion surgery as a consequence. |
3,545 | 26,714 | The risk of cardiovascular disease is increased in rheumatoid arthritis (RA). A meta-analysis showed increased intima media thickness (IMT) in RA. It has been shown that disease modifying antirheumatic drugs (DMARDs) may influence the progression of atherosclerosis. However, it was suggested that biologics may be more efficient than other DMARDs (including methotrexate--MTX) in protecting against atherosclerosis.
The aim of this study was to assess the influence of different RA characteristics and treatment regimens on IMT and atherosclerotic plaques.
317 RA patients and 111 controls were included in the study. IMT was measured in carotid (CIMT) and femoral (FIMT) arteries. Arteries were screened for the presence of plaques.
CIMT, FIMT, and prevalence of plaques were lower in patients treated with methotrexate (MTX) ≥ 20 mg/wk, cyclosporine (CsA), or biologics than in patients treated with lower doses of MTX and other disease modifying antirheumatic drugs. No differences in IMT between patients treated with MTX ≥ 20 mg/wk, biologics, or CsA were found. | We found a beneficial effect of MTX ≥ 20 mg/wk, biologics, and CsA on atherosclerosis. We do not confirm a stronger influence of biologics on IMT compared with therapeutic doses of MTX. |
3,546 | 54,737 | To identify the most significant salivary biomarkers in Sjögren's syndrome (SS) using proteomic methods.
Parotid saliva from 20 non-SS subjects and 41 primary SS patients was analysed. Protein expression profiles for each sample were generated by surface-enhanced laser desorption/ionization time-of-flight-mass spectrometry (SELDI-TOF-MS). Mean peak intensities of SS patients and non-SS subjects were compared by univariate analyses. Samples pooled by diagnosis (SS and non-SS) and labelled with different Cy dyes were compared by two-dimensional difference gel electrophoresis (2D-DIGE). Two protein levels that were most significantly different by SELDI-TOF-MS and 2D-DIGE were validated by enzyme-linked immunosorbent assay in individual samples.
SELDI-TOF-MS of 10-200 kDa peaks revealed eight peaks with >2-fold changes in the SS group that differed from non-SS at P < 0.005. Peaks of 11.8, 12.0, 14.3, 80.6 and 83.7 kDa were increased, while 17.3, 25.4, and 35.4 kDa peaks were decreased in SS samples. 2D-DIGE identified significant increases of beta-2-microglobulin, lactoferrin, immunoglobulin (Ig) kappa light chain, polymeric Ig receptor, lysozyme C and cystatin C in all stages of SS. Two presumed proline-rich proteins, amylase and carbonic anhydrase VI, were reduced in the patient group. Three of these ten biomarkers have not been associated previously with SS. | The salivary proteomic profile of SS is a mixture of increased inflammatory proteins and decreased acinar proteins when compared with non-SS. Future studies will test the ability of these biomarker levels, alone and in combination, to diagnose the salivary component of SS. |
3,547 | 12,438 | Chondrocyte apoptosis is a central pathological feature of cartilage in osteoarthritis (OA). Accumulating evidence suggests that calcium ions (Ca2+) are an important regulator of apoptosis. Previously, we reported that the transient receptor potential channel vanilloid (TRPV5) is upregulated in monoiodoacetic acid (MIA)-induced OA articular cartilage.
The protein levels of TRPV5, phosphorylated Ca2+/calmodulin-dependent kinase II (p-CaMKII), and total CaMKII were detected in vivo using western blotting techniques. Primary chondrocytes were isolated and cultured in vitro. Then, p-CAMKII was immunolocalized by immunofluorescence in chondrocytes. Fluo-4AM staining was used to assess intracellular Ca2+. Annexin V-fluorescein isothiocyanate / propidium iodide flow cytometric analysis was performed to determine chondrocyte apoptosis. Western blotting techniques were used to measure the expression of apoptosis-related proteins.
We found that ruthenium red (aTRPV5inhibitor)or(1-[N,O-bis-(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperaze (KN-62) (an inhibitor of Ca2+/calmodulin-dependent kinase II (CaMKII) phosphorylation) can relieve or even reverse OA in vivo. We found that TRPV5 has a specific role in mediating extracellular Ca2+ influx leading to chondrocyte apoptosis in vitro. The apoptotic effect in chondrocytes was inhibited by KN-62. We found that activated p-CaMKII could elicit the phosphorylation of extracellular signal-regulated protein kinase 1/2, c-Jun N-terminal kinase, and p38, three important regulators of the mitogen-activated protein kinase (MAPK) cascade. Moreover, we also showed that activated p-CaMKII could elicit the phosphorylation of protein kinase B (Akt) and two important downstream regulators of mammalian target of rapamycin (mTOR): 4E-binding protein, and S61 kinase. | Our results demonstrate that upregulated TRPV5 may be an important initiating factor that activates CaMKII phosphorylation via the mediation of Ca2+ influx. In turn, activated p-CaMKII plays a critical role in chondrocyte apoptosis via MAPK and Akt/mTOR pathways. |
3,548 | 7,658 | This study aimed to identify factors associated with rotational mismatch after total knee arthroplasty (TKA) using fixed-bearing posterior stabilized prosthesis and to evaluate the impact of the rotational mismatch on clinical outcomes.
This retrospective cohort study included 159 cases that underwent TKA. Whole-leg computed tomography images were obtained 2 weeks after TKA, with three-dimensional measures of alignment. Rotational alignment of the femoral and tibial components and rotational mismatch between components and between the femur and tibia bones were evaluated. The new Knee Society Score (KSS) was obtained at the final outpatient visit, which was defined as the final follow-up timepoint. Predictive factors were identified for rotational mismatch of the lower extremity and poor new KSS.
The mean follow-up period was 42 ± 16 months. Rotational mismatch ≥ 10° between bones was identified in 56 cases (35%), with a mean mismatch angle of 5.0° ± 9.1° of external rotation of the tibia relative to the femur. Rotational mismatch ≥ 10° between components was identified in three cases (2%; mean 0.3° ± 3.6° of internal tibial rotation). A multivariate regression analysis showed that component malrotation was predictive of post-operative rotational mismatch between bones (p < 0.01) and rotational mismatch ≥ 10° associated with poor new KSS (odds ratio 4.22; p < 0.01).
III. | Malrotation of the fixed-bearing posterior stabilized TKA causes a rotational mismatch between the femur and tibia bones. Excessive rotational mismatch between bones greater than 10° is a risk factor for poor postoperative functional outcome. Precise component positioning is essential for improving TKA outcomes. |
3,549 | 53,568 | Depression and anxiety is prevalent among patients with dementia but the extent to which these conditions are treated with antidepressants has not previously been investigated.
Nationwide register-based data in Denmark were used to identify all patients diagnosed with dementia or osteoarthritis at hospital admission or at first outpatient contact during the period 1995-2000. Rates of subsequent purchase of antidepressants from pharmacies were then calculated. Further, the rate of antidepressant use for patients with dementia was compared with the rate in a gender-, age-, and calendar-matched sample of the general population.
In total, 24,137 patients with a main diagnosis of dementia and 100,378 patients with a main first diagnosis of osteoarthritis were incorporated in the study. A total of 43.2% of patients with dementia received antidepressants during follow-up compared to 16.0% of patients with osteoarthritis. Among patients with a diagnosis of dementia, the rate of subsequently purchasing antidepressants was 4.17 times higher (95% CI = 4.05-4.29) than that of patients with a first diagnosis of osteoarthritis, and 8.85 times higher (95% CI = 8.68-9.03) than that of a gender-, age- and calendar-matched sample of the general population. The rate was increased in all subgroups of patients regardless of gender, age, socio-economic group and time since diagnosis. | The findings challenge the widely held contention that depression and anxiety in patients with dementia is underdiagnosed and undertreated in clinical practice. |
3,550 | 29,895 | Cigarette smoking increases the risk of seropositive adult rheumatoid arthritis. The relationship of smoking with juvenile idiopathic arthritis (JIA), a heterogeneous group of 7 mutually exclusive categories of chronic childhood inflammatory arthritides, is unknown. Our objective was to evaluate the association between JIA and its categories with maternal prenatal smoking.
This case-control study used International Classification of Diseases, Ninth Revision codes from hospital records to identify 1,196 JIA cases born in Washington state and diagnosed at a quaternary pediatric center from 1997-2010. Controls (n = 5,618) were randomly selected from birth records of children without JIA, frequency matched on birth year. Prenatal smoking exposure was assessed from subjects' birth certificates. Chart review categorized JIA into International League of Associations for Rheumatology categories. Adjusted odds ratios (OR) and 95% confidence intervals (95% CIs) were calculated using logistic regression.
We did not observe an increased risk of JIA in relation to maternal prenatal smoking. Prenatal smoking was reported less often among mothers of JIA cases (11%), than among control mothers (17%; OR 0.71 [95% CI 0.58-0.87]), a relationship somewhat more marked for oligoarticular/extended oligoarticular JIA. Although this relationship persisted after adjustment, we cannot rule out that the effect may have been due to residual confounding by socioeconomic status. | We did not observe an increased risk of JIA or its individual categories with maternal prenatal smoking. |
3,551 | 30,968 | Total Hip Arthroplasty (THA) is being used more commonly in younger higher demand patients. The purpose of this randomized pilot study was to explore a) feasibility of comprehensive postoperative rehabilitation compared to usual care following primary THA in subjects <65 years, b) appropriate outcome measures including performance-based measures and c) timing of assessments.
21 subjects who underwent primary THA were randomized to receive a three-month out-patient rehabilitation program (Intervention) or usual postoperative care (Control). Subjects were assessed preoperatively, six-weeks postoperatively (Pre-intervention) and four and 12 months postoperatively (Post-intervention). Self-report measures were the Western Ontario McMaster Osteoarthritis Index (WOMAC) and Rand 36-Item Health Survey (RAND-36). Performance-based measures included lower extremity strength, walking speed and endurance, and gait laboratory assessment.
Ten Control and 11 Intervention subjects with an average age of 53.4 (SD9.3) years were randomized. All Intervention subjects completed the program without adverse effects. Although no statistically significantly results were reported, four months postoperatively, Intervention subjects had clinically important differences (CID) in strength compared with Control subjects. Walking endurance, WOMAC and RAND scores improved significantly with no CID noted between groups. Ten (48%) subjects reported a ceiling effect on the WOMAC (9 (43%) subjects on Pain; 1 (5%) subject on Function). No group CID were noted in gait measures. | Our recommendations would be that performance-based strength measures should be considered for the primary outcome in this younger cohort. Because of the ceiling effects with WOMAC Pain, a different pain measure is indicated. Other more challenging functional performance-based tests should be considered such as a more prolonged endurance test. There is merit in one-year follow-up as strength improved after four months in both groups. |
3,552 | 34,699 | Functional magnetic resonance imaging (fMRI) technology was used to study changes to the resting state blood flow in the brains of patients with knee osteoarthritis (KOA) before and after treatment with moxibustion at the acupoint of the left Dubi (ST 35) and to probe the cerebral mechanism underlying the effect of moxibustion.
The resting state brain function of 30 patients with left KOA was scanned with fMRI before and after treatment with moxibustion. The analytic methods of fractional amplitude of low frequency fluctuation (fALFF) and regional homogeneity (ReHo) were used to observe changes in resting state brain function.
The fALFF values of the right cerebrum, extra-nucleus, left cerebellum, left cerebrum and white matter of patients after moxibustion treatment were higher than before treatment, and the fALFF values of the precentral gyrus, frontal lobe and occipital lobe were lower than before treatment (P < 0.05, K > or = 85). The ReHo values of the thalamus, extra-nucleus and parietal lobe of patients were much higher than those before moxibustion treatment, and the ReHo values of the right cerebrum, left cerebrum and frontal lobe were lower than before treatment (P < 0.05, K > or = 85). | The influence of moxibustion on obvious changes in brain regions basically conforms to the way that pain and warmth is transmitted in the body, and the activation of sensitive systems in the body may be objective evidence of channel transmission. The regulation of brain function by moxibustion is not in a single brain region but rather in a network of many brain regions. |
3,553 | 28,050 | To evaluate the association between radiographically-assessed knee osteoarthritis and femoral neck bone characteristics in women with mild knee radiographic osteoarthritis and those without radiographic osteoarthritis.
Ninety postmenopausal women (mean age [SD], 58 [4] years; height, 163 [6] cm; weight, 71 [11] kg) participated in this cross-sectional study. The severity of radiographic knee osteoarthritis was defined using Kellgren-Lawrence grades 0=normal (n=12), 1=doubtful (n=25) or 2=minimal (n=53). Femoral neck bone mineral content (BMC), section modulus (Z), and cross-sectional area (CSA) were measured with DXA. The biochemical composition of ipsilateral knee cartilage was estimated using quantitative MRI measures, T2 mapping and dGEMRIC. The associations between radiographic knee osteoarthritis grades and bone and cartilage characteristics were analyzed using generalized linear models.
Age-, height-, and weight-adjusted femoral neck BMC (p for linearity=0.019), Z (p for linearity=0.033), and CSA (p for linearity=0.019) increased significantly with higher knee osteoarthritis grades. There was no linear relationship between osteoarthritis grades and knee cartilage indices. | Increased DXA assessed hip bone strength is related to knee osteoarthritis severity. These results are hypothesis driven that there is an inverse relationship between osteoarthritis and osteoporosis. However, MRI assessed measures of cartilage do not discriminate mild radiographic osteoarthritis severity. |
3,554 | 22,411 | Dynamic balance and quiet standing balance are decreased in knee osteoarthritis (OA), with dynamic balance being more affected. This study aimed to investigate the effectiveness of a group exercise programme of lower extremity muscles integrated with education on dynamic balance using the Star Excursion Balance test (SEBT) in knee OA.
Experimental before-and-after pilot study design. Nineteen participants with knee OA attended the exercise sessions once a week for six weeks, in addition to home exercises. Before and after the exercise programme, dynamic balance was assessed using the SEBT in the anterior and medial directions in addition to hip and knee muscle strength, pain, and function.
Fourteen participants completed the study. Dynamic balance on the affected side demonstrated significant improvements in the anterior and medial directions (p=0.02 and p=0.01, respectively). The contralateral side demonstrated significant improvements in dynamic balance in the anterior direction (p<0.001). However, balance in the medial direction did not change significantly (p=0.07). Hip and knee muscle strength, pain, and function significantly improved (p<0.05) after the exercise programme. | This is the first study to explore the effect of an exercise programme on dynamic balance using the SEBT in knee OA. The exercise programme was effective in improving dynamic balance which is required in different activities of daily living where the patients might experience the risk of falling. This might be attributed to the improvement in muscle strength and pain after the exercise programme. |
3,555 | 2,002 | The optimal interval between staged bilateral total knee arthroplasty (STBTKA) is unclear. Studies have reported STBTKA being performed at the same admission, with a seven day interval. The safety and outcomes of patients submitted to same-admission STBTKA (SA-STBTKA) are questionable and need further investigation.
A prospective non-randomized study was performed to compare the early postoperative outcomes, systemic complications, and surgical-related complications between the first and second knees, as well as between SA-STBTKA and STBTKA groups. From July 2018 to November 2019, a total of 430 patients were recruited. Analyzed parameters included the Knee Society score (KSS), Knee Society functional score (KSFS), range of motion (ROM), Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score, WOMAC stiffness score, and WOMAC score for daily life difficulty.
Pre-operatively, the demographic data and functional scores were not significantly different between the two groups. The KSS, WOMAC pain score, and WOMAC stiffness score of the second knee in the STBTKA group were significantly better than those of the first knee. A total of 426 patients completed the last follow-up one year after surgery, and the post-operative functional scores were not significantly different between the two groups and between the two knees within the same group. Before the second operation, more systemic complications were identified in the SA-STBTKA group, while the rate of surgical complication was not significantly different when compared to STBTKA patients. | With equivalent post-operative function and a higher frequency of minor complications, SA-STBTKA should be cautiously selected as a treatment option for bilateral osteoarthritis. |
3,556 | 42,923 | This study aimed to establish the effects of hospital- and home-based proprioceptive and strengthening exercise programs on proprioception, pain, and functional status in patients with knee osteoarthritis (OA).
Sixty patients with bilateral knee OA were randomly allocated into either a home-based or hospital-based exercise program. Hospital-based exercise group (n=30, mean age 50.23±9.07 years) received functional training program with proprioceptive ability, ice, and home exercises. Home-based exercise group (n=30, mean age 54.4±7.9 years) had a program of ice and home exercises. Treatment programs was conducted 5 days per week for 6 weeks (30 sessions). Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Monitorized Functional Squat System-Proprioceptive Test (MFSS), timed performance test (TUG), and visual analogue scale (VAS) for the intensity of pain were used to quantify the variables.
Both groups demonstrated significant improvement when pre- and post-treatment results were compared for pain intensity, WOMAC, and TUG test scores (p<0.05). No statistically significant improvement was found in proprioception of the home-based group (p>0.05). Hospital-based group demonstrated significantly greater improvement in MFSS, TUG test, and VAS in activity when compared with the home-based group (p<0.05). | Both hospital- and home-based exercise programs decreased joint symptoms and improved function in patients with knee OA. |
3,557 | 63,836 | To determine whether polymorphism in the manganese superoxide dismutase (MnSOD) gene is associated with susceptibility or disease outcome in rheumatoid arthritis (RA).
We used a case-control approach with 153 RA patients and 218 control subjects to examine for any associations between MnSOD genotypes and susceptibility to RA. We also investigated the influence of genotypes on radiologic outcome, as measured using the Larsen score for radiographs of the hands and feet, and on functional outcome, as assessed by the Health Assessment Questionnaire. MnSOD typing was carried out using polymerase chain reaction-based methods. Results were analyzed using multiple regression analysis, with adjustment for age, sex, and disease duration. In separate analyses, we corrected for rheumatoid factor (RF) status and/or the presence of the HLA-DRB1 "shared epitope" (SE). We also examined whether radiologic outcome was influenced by interactions between MnSOD and glutathione S-transferase (GST) genes.
No association between MnSOD genotype and development of RA was found. The MnSOD VV genotype was associated with a significantly higher (P = 0.04) Larsen score (104.4) than MnSOD AA (83.0), while MnSOD AV was associated with an intermediate score (91.8). Correction for RF status had no significant effect on the results of the analysis, but significance was lost (P = 0.09) after correction for the presence of the SE. There was evidence of interaction between the GSTT1 and MnSOD genotypes, with the MnSOD VV/GSTT1-null combination being associated with the highest Larsen score (142.1; P = 0.007 after correction for the SE). | Polymorphism in the MnSOD gene is not associated with susceptibility to RA. Our data suggest that MnSOD VV is associated with more severe radiologic outcome, although this relationship may not be independent of the effect of the SE. However, interaction between MnSOD and GST genes appears to influence radiologic outcome independently of the SE. |
3,558 | 57,396 | To determine matrix metalloproteinase-8 (MMP-8) secretion from rheumatoid arthritis (RA) peripheral blood polymorphonuclear leucocytes (PMNs), in response to immune complexes (IC), cytokines and their combinations, and to study correlation of serum MMP-8 with disease activity.
PMNs from RA patients and controls were stimulated in vitro with interleukin-15 (IL-15), IL-18, adherent immune complexes, rabbit anti-human immunoglobulin G (anti-HIgG), human immunoglobulin G (HIgG), and their F (ab') 2 prongs, phorbol myristate acetate (PMA) or combinations of above. Supernatants from these experiments and sera from both groups were assayed for MMP-8 using ELISA and correlated with disease activity measures in patients.
MMP-8 secretion from stimulated PMNs was compared to unstimulated PMNs. Immune complexes elicited significant MMP-8 secretion (p = 0.006 and 0.001, control and RA respectively). Unlike HIgG and its F (ab')2 fragment, very high secretion was elicited by anti-HIgG (242.37 +/- 10.85 ng/ml) and its F (ab')2 prong (195.85 +/- 28.67 ng/ml). IL-15 did not elicit any secretion. IL-18 with PMA increased secretion significantly only from RA PMNs (p = 0.003). Serum MMP-8 correlated positively with serum CRP (p = 0.017) and not with disease activity score (p = 0.199). | We for the first time demonstrate that immune complexes elicit MMP-8 secretion from PMNs. Except for higher secretion from RA PMNs in response to combination of IL-18 and PMA, both control and RA PMNs respond similarly to various stimuli. Secretion by anti-HIgG occurs by a mechanism independent of Fc receptor. Correlation with CRP suggest that serum MMP-8 may be an indicator of acute inflammatory activity. |
3,559 | 48,770 | Investigating the association between plasma levels of cytokines and chemokines, Selenoprotein S (SELS) gene variation and osteoarthritis (OA) subtypes.
The genetics of osteoarthritis and progression (GARP) study consists of 191 sibling pairs with symptomatic OA at multiple joint sites. We have measured plasma levels of 17 cytokines and chemokines and genetic variation at the SELS gene.
Nine out of 17 serum markers could be assessed quantitatively, whereas eight markers were assessed qualitatively. Principal component analysis (PCA) on the quantitatively assessed markers and serum high sensitive C-reactive protein (S-HsCRP) revealed that three components underlie 61% of the total plasma variation. Three single nucleotide polymorphisms (SNPs) in the SELS gene revealed four common haplotypes, one of which, GAG (frequency 3.5%) showed significant association to an anti-inflammatory (P=0.019) and acute phase related (P=0.036) component. OA subtype analysis showed that one component (mainly representing chemokine variation) was significantly associated to hand OA and disc degeneration (P=0.029 and P=0.010 respectively) as well as a physical component score (PCS) (P=0.042). The CRP related component also showed a strong association to the PCS (P=0.007). SELS haplotypes showed no association to OA subtypes in the GARP study. | Genetic variation in the SELS gene associates to components representing inflammatory signaling. Another component, representing chemokine variation, showed association to hand OA and disc degeneration in the GARP study indicating chemokines may contribute to OA pathogenesis. |
3,560 | 2,924 | To determine the impact of difficult-to-treat rheumatoid arthritis (D2T RA) on (costs related to) healthcare utilization, other resource use and work productivity.
Data regarding healthcare utilization, other resource use and work productivity of 52 D2T (according to the EULAR definition) and 100 non-D2T RA patients were collected via a questionnaire and an electronic patient record review during a study visit. Annual costs were calculated and compared between groups. Multivariable linear regression analysis was performed to assess whether having D2T RA was associated with higher costs.
Mean (95% CI) annual total costs were €37 605 (€27 689 - €50 378) for D2T and €19 217 (€15 647 - €22 945) for non-D2T RA patients (P<0.001). D2T RA patients visited their rheumatologist more frequently, were more often admitted to day-care facilities, underwent more laboratory tests and used more drugs (specifically targeted synthetic DMARDs), compared with non-D2T RA patients (P<0.01). In D2T RA patients, the main contributors to total costs were informal help of family and friends (28%), drugs (26%) and loss of work productivity (16%). After adjustment for physical functioning (HAQ), having D2T RA was no longer statistically significantly associated with higher total costs. HAQ was the only independent determinant of higher costs in multivariable analysis. | The economic burden of D2T RA is significantly higher than that of non-D2T RA, indicated by higher healthcare utilization and higher annual total costs. Functional disability is a key determinant of higher costs in RA. |
3,561 | 23,096 | Gout is associated with dyslipidaemia. Association of the apolipoprotein A1-C3-A4 gene cluster with gout has previously been reported in a small study. To investigate a possible causal role for this locus in gout, we tested the association of genetic variants from APOA1 (rs670) and APOC3 (rs5128) with gout.
We studied data for 2452 controls and 2690 clinically ascertained gout cases of European and New Zealand Polynesian (Māori and Pacific) ancestry. Data were also used from the publicly available Atherosclerosis Risk in Communities study (n = 5367) and the Framingham Heart Study (n = 2984). Multivariate adjusted logistic and linear regression was used to test the association of single-nucleotide polymorphisms with gout risk, serum urate, triglyceride and high-density lipoprotein cholesterol (HDL-C).
In Polynesians, the T-allele of rs670 (APOA1) increased (odds ratio, OR = 1.53, P = 4.9 × 10(-6)) and the G-allele of rs5128 (APOC3) decreased the risk of gout (OR = 0.86, P = 0.026). In Europeans, there was a strong trend to a risk effect of the T-allele for rs670 (OR = 1.11, P = 0.055), with a significant protective effect of the G-allele for rs5128 being observed after adjustment for triglycerides and HDL-C (OR = 0.81, P = 0.039). The effect at rs5128 was specific to males in both Europeans and Polynesians. Association in Polynesians was independent of any effect of rs670 and rs5128 on triglyceride and HDL-C levels. There was no evidence for association of either single-nucleotide polymorphism with serum urate levels (P ⩾ 0.10). | Our data, replicating a previous study, supports the hypothesis that the apolipoprotein A1-C3-A4 gene cluster plays a causal role in gout. |
3,562 | 41,011 | To develop and validate a magnetic resonance imaging (MRI) method of assessment of joint space narrowing (JSN) in rheumatoid arthritis (RA).
Phase A: JSN was scored 0-4 on MR images of 5 RA patients and 3 controls at 15 wrist sites and 2nd-5th metacarpophalangeal (MCP) joints by 8 readers (7 once, one twice), using a preliminary scoring system. Phase B: Image review, discussion, and consensus on JSN definition, and revised scoring system. Phase C: MR images of 15 RA patients and 4 controls were scored using revised system by 5 readers (4 once, one twice), and results compared with radiographs [Sharp-van der Heijde (SvdH) method].
Phase A: Intraobserver agreement: intraclass correlation coefficient (ICC) = 0.99; smallest detectable difference (SDD, for mean of readings) = 2.8 JSN units (4.9% of observed maximal score). Interobserver agreement: ICC = 0.93; SDD = 6.4 JSN units (9.9%). Phase B: Agreement was reached on JSN definition (reduced joint space width compared to normal, as assessed in a slice perpendicular to the joint surface), and revised scoring system (0-4 at 17 wrist sites and 2nd-5th MCP; 0: none; 1: 1-33%; 2: 34-66%; 3: 67-99%; 4: ankylosis). Phase C: Intraobserver agreement: ICC = 0.90; SDD = 6.8 JSN units (11.0%). Interobserver agreement: ICC = 0.92 and SDD = 6.2 JSN units (8.7%). The correlation (ICC) with the SvdH radiographic JSN score of the wrist/hand was 0.77. Simplified approaches evaluating fewer joint spaces demonstrated similar reliability and correlation with radiographic scores. | An MRI scoring system of JSN in RA wrist and MCP joints was developed and showed construct validity and good intra- and interreader agreements. The system may, after further validation in longitudinal data sets, be useful as an outcome measure in RA. |
3,563 | 47,608 | The present study aimed to assess neuropathic symptoms, their stability over time and relationship to pain intensity, pain distribution, and emotional distress in patients with musculoskeletal disorders.
This is a prospective study.
The study was done at the Department of Physical Medicine and Rehabilitation at Ulleval University Hospital.
Eighty-six subjects between 18 years and 70 years with chronic musculoskeletal pain participated. Forty-nine subjects had widespread pain and 39 subjects fulfilled the American College of Rheumatology (ACR) criteria for fibromyalgia.
McGill pain drawing, pain intensity (visual analog scales), emotional distress (Hopkins Symptom Checklist v 25), and fibromyalgia impact questionnaire were the recorded predictors, and neuropathic symptoms (Leeds assessment of neuropathic symptoms and signs-LANSS) were the main outcome variable which was assessed over 4 months.
The mean LANSS score was 6.7 (standard deviation 5.6). Thirteen percent of the subjects had a score of 12 or more. Self-reported LANSS symptoms did not change over the 4 months follow-up, and the reliability of measurements as evaluated by intraclass correlation coefficient was 0.78. In a backward multiple regression analysis, the presence of fibromyalgia diagnosis and emotional distress remained the final predictors for neuropathic symptoms. | Our study demonstrates that neuropathic symptoms are prominent features of chronic musculoskeletal pain and are stable over time. These symptoms were closely related to emotional distress and to the diagnosis of fibromyalgia. The results lend support to the theory that neuropathic symptoms represent an underlying sensitization. |
3,564 | 18,141 | To evaluate the effectiveness and safety of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, establishing the optimized regimen and switching from intravenous (IV) to subcutaneous (SC) therapy.
Retrospective observational study. We included 53 RA patients treated with TCZ. The main outcome was TCZ effectiveness at week 24. Secondary outcome variables included effectiveness at week 52, therapeutic maintenance, physical function and safety. The effectiveness of optimization and the switch from IV to SC was evaluated at 3 and 6 months. The efficacy was measured with the Disease Activity Score. Paired t-tests or Wilcoxon were used to evaluate effectiveness and survival time using Kaplan-Meier.
The proportion of patients who achieved remission or low disease activity at weeks 24 and 52 was 75.5% and 87.3%, respectively. The mean retention time (95% confidence interval [95% CI] was 81.7 months [76.6-86.7]). Twenty-one of 53 patients (39.6%) optimized the TCZ dose and 35 patients switched from IV TCZ to SC, with no changes in effectiveness. The adverse event rate was 13.6 events/100 patient-years. | Tocilizumab appears to be effective and safe in RA in clinical practice. The optimized regimen appears to be effective in most patients in remission, even when they change from IV to SC. |
3,565 | 11,418 | Consensus guidelines are not available for the use of immunoglobulin replacement therapy (IGRT) in patients developing iatrogenic secondary antibody deficiency following B-cell targeted therapy (BCTT) in autoimmune rheumatic disease.
To evaluate the role of IGRT to manage hypogammaglobulinemia following BCTT in autoimmune rheumatic disease (AIRD).
Using an agreed search string we performed a systematic literature search on Medline with Pubmed as vendor. We limited the search to English language papers with abstracts published over the last 10 years. Abstracts were screened for original data regarding hypogammaglobulinemia following BCTT and the use of IGRT for hypogammaglobulinemia following BCTT. We also searched current recommendations from national/international organisations including British Society for Rheumatology, UK Department of Health, American College of Rheumatology, and American Academy of Asthma, Allergy and Immunology.
222 abstracts were identified. Eight papers had original relevant data that met our search criteria. These studies were largely retrospective cohort studies with small patient numbers receiving IGRT. The literature highlights the induction of a sustained antibody deficiency, risk factors for hypogammaglobulinemia after BCTT including low baseline serum IgG levels, how to monitor patients for the development of hypogammaglobulinemia and the limited evidence available on intervention thresholds for commencing IGRT. | The benefit of BCTT needs to be balanced against the risk of inducing a sustained secondary antibody deficiency. Consensus guidelines would be useful to enable appropriate assessment prior to and following BCTT in preventing and diagnosing hypogammaglobulinemia. Definitions for symptomatic hypogammaglobulinemia, intervention thresholds and treatment targets for IGRT, and its cost-effectiveness are required. |
3,566 | 65,717 | To determine the prevalence of sicca symptoms and Sjögren's syndrome (SS) in spondyloarthropathy (SpA) patients with ankylosing spondylitis (AS) and undifferentiated SpA (uSpA).
Patients with SpA with inflammatory back pain and/or peripheral arthritis presenting to the university outpatient clinic were diagnosed as AS (n = 40) and uSpA (n = 65) according to established criteria. Patients with SpA with sicca symptoms and/or positive antinuclear antibody (ANA) were investigated for SS by minor salivary gland biopsy and/or sialography. To assess sicca symptoms in this cohort systematically we mailed a validated questionnaire with 6 questions on dryness of eyes and mouth to all 105 SpA patients and 150 healthy controls, a positive answer to > or = 3 questions was taken as suggestive of SS. There was no significant difference in baseline characteristics between patients and controls.
In 8/105 SpA patients (5 uSpA, 3 AS; 6 female, 2 male) SS diagnosis by the European criteria indicated a frequency of 7.6%. Of 105 SpA patients, 12 were ANA+ (11.4%), of whom 7 had SS; thus, ANA were detected in 7/8 SpA patients with SS (88%). Of the 84 SpA patients responding to the questionnaire (80%), 10 gave a positive answer to > or = 3 questions (11.9%) compared to 2 of 131 (1.5%) controls (87.3%) (odds ratio = 8.7, 95% CI 2.3-32.5, p < 0.01). | The data suggest increased prevalence of sicca symptoms and SS in SpA patients with AS and uSpA. The occurrence of a secondary SS in a variety of inflammatory diseases suggests that salivary gland involvement in these conditions results from as yet unidentified shared pathogenic mechanisms resulting in nonspecific inflammation in this location. |
3,567 | 35,997 | Osteoporosis is a metabolic disorder characterized by a reduction in bone mass and deterioration in the microarchitectural structure of the bone, leading to a higher risk for spontaneous and fragility fractures.The main aim was to study the differences between human bone from osteoporotic and osteoarthritic patients about gene expression (osteogenesis and apoptosis), bone mineral density, microstructural and biomechanic parameters.
We analyzed data from 12 subjects: 6 with osteoporotic hip fracture (OP) and 6 with hip osteoarthritis (OA), as the control group. All subjects underwent medical history, analytical determinations, densitometry, histomorphometric and biochemical study. The expression of 86 genes of osteogenesis and 86 genes of apoptosis was studied in pool of bone samples from patients with OP and OA by PCR array.
We observed that most of the genes of apoptosis and osteogenesis show a decrease in gene expression in the osteoporotic group in comparison with the osteoarthritic group. The histomorphometric study shows a lower bone quality in the group of patients with hip fractures compared to the osteoarthritic group. | The bone tissue of osteoporotic fracture patients is more fragile than the bone of OA patients. Our results showed an osteoporotic bone with a lower capacities for differentiation and osteoblastic activity as well as a lower rate of apoptosis than osteoarthritic bone. These results are related with structural and biochemical parameters. |
3,568 | 9,202 | Sleep and pain-related experiences are consistently associated, but the pathways linking these experiences are not well understood. We evaluated whether pain catastrophizing and arthritis self-efficacy mediate the association between sleep disturbance and osteoarthritis (OA) symptom severity in patients with knee OA.
We analyzed cross-sectional baseline data collected from Veterans Affairs (VA) patients enrolled in a clinical trial examining the effectiveness of a positive psychology intervention in managing pain from knee OA. Participants indicated how often in the past two weeks they were bothered by trouble falling asleep, staying asleep, or sleeping too much. We used validated scales to assess the primary outcome (OA symptom severity) and potential mediators (arthritis self-efficacy and pain catastrophizing). To test the proposed mediation model, we used parallel multiple mediation analyses with bootstrapping, controlling for sociodemographic and clinical characteristics with bivariate associations with OA symptom severity.
The sample included 517 patients (Mage = 64 years, 72.9% male, 52.2% African American). On average, participants reported experiencing sleep disturbance at least several days in the past two weeks (M = 1.41, SD = 1.18) and reported moderate OA symptom severity (M = 48.22, SD = 16.36). More frequent sleep disturbance was associated with higher OA symptom severity directly (b = 3.08, P <0.001) and indirectly, through higher pain catastrophizing (b = 0.60, 95% confidence interval [CI] = 0.20 to 1.11) and lower arthritis self-efficacy (b = 0.84, 95% CI = 0.42 to 1.42). | Pain catastrophizing and arthritis self-efficacy partially mediated the association between sleep disturbance and OA symptom severity. Behavioral interventions that address pain catastrophizing and/or self-efficacy may buffer the association between sleep disturbance and OA symptom severity. |
3,569 | 38,975 | To assess the clinical characteristics and outcome of a rheumatic fever case-series from a referral hospital over the last 20 years.
Patients under the age of 18 years, diagnosed with rheumatic fever between 1986 and 2007 were retrospectively assessed to estimate the carditis and relapse rates, by use of descriptive and survival analysis.
Of 178 cases identified, 134 were included. During the acute phase, 66.4% had polyarthritis, 56.8% had carditis, 28.6% had chorea, 1.5% had subcutaneous nodules, and 1.5% had erythema marginatum. The association of carditis and arthritis occurred in 40%. Carditis and chorea were more frequent among female gender. High antistreptolysin-O titres were found in 58.3%, and family history of rheumatic fever, in 14.5%. Mean follow-up was 6.8 years (1.1 to 16.9). Relapse was observed in 15%, hospital admissions in 27.6%, and follow-up discontinuation in 47.4% after a mean of 5.1 years. Carditis and relapse probabilities were 17.5% and 13.2%, respectively, five years after the initial attack. | The risk of carditis and relapse of rheumatic fever was higher within the first five years. Follow-up discontinuation was frequent, pointing to the need of measures to improve adherence to prophylaxis and follow-up. |
3,570 | 9,571 | To investigate the influence of micro ribonucleic acid (miR)-21 on rats with rheumatoid arthritis (RA) through the Wnt signaling pathway.
A total of 30 rats were divided into three groups: control group (healthy rats, n=10), model group (rat model of RA, n=10), and MiR group (rat model of RA injected with miR-21 lentivirus, n=10). The paw volume, arthritis indexes, and protein expression level in each group were analyzed by means of paw volume and arthritis index measurement, reverse transcription-polymerase chain reaction (RT-PCR) assay, and fluorescent Western blotting.
The expression levels of inflammatory factors declined in MiR group compared with those in model group, while they were higher in model group than those in control group and MiR group (p<0.05). At 15 d after transfection with lentivirus, the paw volume in MiR group was smaller than that in model group, which was decreased markedly with the extended time of transfection (p<0.05). On the 30th d, MiR group had a remarkably smaller paw volume than model group. In comparison with that in control group, the paw volume in model group was increased notably from the 7th d and displayed a significant difference in the 30th d (p<0.05). The arthritis indexes in MiR group were lower than those in model group; however, there were no apparent inflammations at the joints at 15 d after drug administration. Moreover, the longer the time of drug administration was, the less apparent the inflammations at the joints will be. The inflammations at the joints were ameliorated evidently on the 30th d in MiR group (p<0.05). Compared with those in control group, the inflammations in model group were increased significantly from the 7th d, with significant differences in the 30th d (p<0.05). The messenger RNA (mRNA) expression levels of interleukin-6 (IL-6), IL-8, and Wnt in MiR group were higher than those in control group, but lower than those in model group (p<0.05), while they were higher in model group than those in control group (p<0.05). The expression level of Wnt protein was decreased in MiR group compared with that in model group (p<0.05), and model group had a prominently elevated expression level of Wnt protein in comparison with control group (p<0.05). | MiR-21 overexpression can repress the expressions of IL-6 and IL-8 and relieve the symptoms of RA by down-regulating the Wnt signal. |
3,571 | 62,037 | Primary fibromyalgia syndrome (PFS) is a nonarticular rheumatological syndrome characterized by disturbances in the hypothalamo-pituitary-adrenal (HPA) axis. The site of the defect in the HPA axis is a matter of debate. Our aim was to evaluate the HPA axis by the insulin-tolerance test (ITT), standard dose (250 microg) ACTH test (SDT) and low dose (1 microg) ACTH test (LDT) in patients with PFS.
Sixteen patients (13 female, three male) with PFS were included in the study. Sixteen healthy subjects (12 female, four male) served as matched controls. ACTH stimulation tests were carried out by using 1 microg and 250 microg intravenous (i.v.) ACTH as a bolus injection after an overnight fast, and blood samples were drawn at 0, 30 and 60 min. The ITT was performed by using i.v. soluble insulin, and serum glucose and cortisol levels were measured before and after 30, 60, 90 and 120 min. The 1 microg and 250 microg ACTH stimulation tests and the ITT were performed consecutively.
Peak cortisol responses to both the low dose test (LDT) and standard dose test (SDT) (589 +/- 100 nmol/l; 777 +/- 119 nmol/l, respectively) were lower in the PFS group than in the control group (1001 +/- 370 nmol/l; 1205 +/- 386 nmol/l, respectively) (P < 0.0001). Peak cortisol responses to ITT (730 +/- 81 nmol/l) in the PFS group were lower than in the control group (1219 +/- 412 nmol/l) (P < 0.0001). Six of the 16 patients with PFS had peak cortisol responses to LDT lower than the lowest peak cortisol response of 555 nmol/l obtained in healthy subjects after LDT. There was a significant difference between the peak cortisol responses to LDT (589 +/- 100 nmol/l) and peak cortisol responses to ITT (730 +/- 81 nmol/l) in the PFS group (P < 0.0001). Peak cortisol responses to SDT (777 +/- 119 nmol/l) were similar to peak cortisol responses to ITT (730 +/- 81 nmol/l) in the PFS group. | We conclude that the perturbation of the HPA axis in PFS is characterized by underactivation of the HPA axis. Some patients with PFS may have subnormal adrenocortical function. LDT is more sensitive than SDT or ITT in the investigation of the HPA axis to determine the subnormal adrenocortical function in patients with PFS. |
3,572 | 62,705 | To investigate the expression and regulation of CD80, CD86, and CD28 costimulatory molecules in sialoadenitis and interstitial nephritis in patients with Sjögren's syndrome (SS).
Expression of CD80, CD86, and CD28 molecules was studied by immunohistochemical staining of lip biopsy specimens obtained from patients who had sialoadenitis associated with SS, and renal biopsy specimens obtained from patients who had interstitial nephritis associated with SS. To elucidate the mechanism of de novo expression of CD80 and CD86 antigens, their induction by cytokines in human salivary duct cell line (HSG) and renal cortical epithelial cells (HRCE) by cell enzyme linked immunosorbent assay (ELISA) was quantitatively investigated.
In patients with severe sialoadenitis, CD80 and CD86 were strongly expressed on ductal epithelial cells. In contrast, these antigens were not found in the minor salivary glands of normal subjects or of patients with mild sialoadenitis. Some infiltrating cells expressed CD28. In patients who had interstitial nephritis associated with SS, some tubular epithelial cells expressed CD86 but not the CD80 antigen. Unstimulated HSG cells did not express CD80 or CD86. Interferon gamma (IFNgamma) consistently up regulated levels of CD80 and CD86. In contrast, tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), IL2, and IL4 had no effect on either CD80 or CD86 levels. Unstimulated HRCE did not express CD80 or CD86. IFNgamma consistently up regulated CD86 expression. No CD80 expression was found on tubular cells. TNFalpha, IL1beta, IL2, and IL4 had no discernible effects. | Salivary ductal cells in patients with SS can express CD80 and CD86 costimulatory molecules in response to IFNgamma. Tubular epithelial cells in patients who have interstitial nephritis associated with SS express only CD86 molecules. In patients with SS, salivary ductal cells and tubular epithelial cells may activate infiltrating CD28 positive T lymphocytes by presenting antigens to T cells, potentially leading to tissue destruction. |
3,573 | 1,707 | Few reports have described the association between rheumatoid arthritis (RA) cervical lesions and osteoporosis, especially in patients with vertical subluxation (VS) that could be induced by the collapse of lateral masses in the upper cervical spine. Therefore, this study aimed to investigate the prevalence and risk factors for cervical lesions in patients with RA under current pharmacological treatments with biological agents, and to investigate the relationship between osteoporosis and VS development.
One hundred eighty-five consecutive patients with RA who underwent both cervical plain radiography and bone mineral density (BMD) scanning were enrolled. RA cervical lesions included atlantoaxial subluxation (AAS), VS, and subaxial subluxation (SAS). We assigned patients with AAS, VS, or SAS to the cervical-lesion group, and all other patients to the non-cervical-lesion group. Radiological findings, BMD, and clinical data on RA were collected. We used multivariate logistic regression analyses to assess the risk factors for cervical lesions in patients with RA.
The cervical-lesion and non-cervical-lesion groups included 106 and 79 patients, respectively. There were 79 patients with AAS, 31 with VS, and 41 with SAS. The cervical-lesion group had a younger age of RA onset, longer RA disease duration, higher RA stage, and lower femoral neck BMD than the non-cervical-lesion group. Multivariate analyses showed that the risk factors for RA cervical lesions were prednisolone usage, biological agent usage, and higher RA stage. Prednisolone usage and femoral neck BMD were the risk factors for VS. | Cervical lesions were confirmed in 57 % of the patients. Prednisolone usage, biological agent usage, and higher RA stage were significant risk factors for cervical lesions in patients with RA. The general status of osteoporosis might contribute to the development of VS. |
3,574 | 23,135 | Emerging evidence suggests that diabetes may be a risk factor for osteoarthritis (OA). However, previous results on the association between diabetes and all OA were conflicting. We aimed to comprehensively analyse the association between type II diabetes mellitus (T2DM) and osteoarthritis of the hand (HOA) specifically.
We conducted a matched (1:1) case-control study using the UK-based Clinical Practice Research Datalink (CPRD) of cases aged 30-90 years with an incident diagnosis of HOA from 1995 to 2013. In multivariable conditional logistic regression analyses, we calculated odds ratios (OR) for incident HOA in patients with T2DM, categorized by T2DM severity (HbA1C), duration, and pharmacological treatment. We further performed sensitivity analyses in patients with and without other metabolic diseases (hypertension (HT), hyperlipidaemia (HL), obesity).
Among 13,500 cases and 13,500 controls, we observed no statistically significant association between T2DM and HOA (OR 0.95, 95% confidence interval (CI) 0.87-1.04), regardless of T2DM severity, duration, or pharmacological treatment. Having HT did not change the OR. Although we observed slightly increased ORs in overweight T2DM patients with co-occurring HL with or without coexisting HT, none of these ORs were statistically significant. | Our results provide evidence that T2DM is not an independent risk factor for HOA. Concurrence of T2DM with HT, HL, and/or obesity did not change this association significantly. |
3,575 | 67,908 | We have reviewed 11 women post-augmentation mammoplasty who were referred to our clinic with diffuse rheumatic complaints. All patients had undergone mammoplasty with silicone gel-filled implants prior to the onset of their locomotor symptoms (mean latency time 7.8 years). One physician interviewed and examined each of these patients following a standardized format for clinical retrieval.
Of the patients reviewed, 6 patients had clinical fibromyalgia based on the ACR criteria, and the remaining 5 patients had symptoms consistent with the "chronic fatigue syndrome." None of our patients were found to have evidence of a defined connective tissue disease. Antinuclear antibodies were detected in 4 (36%) patients and low level titres of extractable nuclear antigens in only 2 (18%). | Previously a causal relationship between the use of silicone gel-filled breast implants and the subsequent development of symptoms referred to as human adjuvant disease (HAD) has been proposed. On the basis of currently accepted criteria we have preferred to diagnose our post-mammoplasty patients without specific connective tissue disease, as having chronic fatigue syndrome (CFS), or when tender points are present, as having fibromyalgia (FMS), rather than implying that such cases represent a separate and unique rheumatological disease entity. In the light of our current understanding of CFS and FMS, a relationship between them and the previous silicone mammoplasty seems possible. |
3,576 | 39,008 | To investigate CD25(-)FOXP3(+) cells in RA patients and their possible relationship with disease features and response to glucocorticoids (GCs).
Peripheral blood mononuclear cells were collected from 147 RA patients, 29 healthy controls and 75 SLE patients as disease controls. The proportion of CD4(+)FOXP3(+) cells with negative, low or high CD25 expression and the levels of IL-10-, TNF-α-, IL-17- and IFNγ-producing cells were assessed by flow cytometry. The presence of the high IL-10 genotype (-1082GG), associated with good response to GC, was determined by PCR amplification and hybridization with allele-specific fluorescently labelled probes. Data were related to treatment and clinical parameters.
The CD25(-)FOXP3(+) population was significantly increased in RA patients and negatively correlated with DAS-28 and other disease parameters. The IL-10 genotype did not influence the frequency of these cells in controls or the entire RA group; however, GC-treated patient carriers of the high IL-10 genotype presented significantly higher levels of this population in addition to an increased percentage of IL-10-secreting cells and relatively low amounts of TNF-α-, IFN-γ- and IL-17-positive cells. Finally, a prospective study confirmed that genetically high IL-10 producers significantly increase CD25(-)FOXP3(+) cells after 6 months of GC treatment. | The present study provides the first evidence of increased CD25(-)FOXP3(+) cells in RA patients, which were associated with disease activity and with GC treatment in carriers of the high IL-10 genotype, suggesting that this population plays a role in the clinical response to prednisone in RA. |
3,577 | 44,965 | Targeting joint destruction induced by osteoclasts (OCs) is critical for management of patients with rheumatoid arthritis (RA). Since phosphoinositide 3-kinase (PI3-K) plays a critical role in osteoclastogenesis and bone resorption, we examined the effects of ZSTK474, a novel phosphoinositide 3-kinase (PI3-K)-specific inhibitor, on murine OCs in vitro and in vivo.
The inhibitory effect of ZSTK474 on OC formation was determined and compared with other PI3-K inhibitors by counting tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells after culturing murine bone marrow monocytic OC precursors, and RAW264.7 cells. Activation of Akt and expression of nuclear factor of activated T cells (NFAT) c1 in cultured RAW264.7 cells were examined. The suppressing effect of ZSTK474 on bone resorption was assessed by the pit formation assay. The in vivo effects of ZSTK474 were studied in collagen-induced arthritis (CIA) in the mouse. Oral daily administration of ZSTK474 was started either when more than half or when all mice developed arthritis. Effects of ZSTK474 were evaluated using the arthritis score and histological score of the hind paws.
ZSTK474 inhibited the differentiation of bone marrow OC precursors and RAW264.7 cells in a dose-dependent manner. The inhibitory effect of ZSTK474 was much stronger than that of LY294002, the most commonly used PI3-K inhibitor. In addition, ZSTK474 suppressed the bone resorbing activity of mature OCs. Moreover, oral daily administration of ZSTK474, even when begun after the development of arthritis, ameliorated CIA in mice without apparent toxicity. Histological examination of the hind paw demonstrated noticeable reduction of inflammation and of cartilage destruction in ZSTK474-treated mice. ZSTK474 also significantly decreased OC formation adjacent to the tarsal bone of the hind paw. | These findings suggest that inhibition of PI3-K with ZSTK474 may potentially suppress synovial inflammation and bone destruction in patients with RA. |
3,578 | 8,748 | Abatacept (ABT) demonstrates good clinical efficacy and retention in rheumatoid arthritis (RA) patients. However, no rescue treatment option against inadequate response to ABT exists. Since tacrolimus (TAC) and ABT suppress T lymphocytes via different mechanisms and a combination of these agents could potentially be effective, this study aimed to examine the efficacy and safety of add-on TAC therapy in RA patients with inadequate response to ABT.
Of 550 patients treated with ABT and registered in a Japanese multicenter registry, 25 consecutive patients who underwent add-on TAC therapy and were followed for longer than 24 weeks were included in this study.
Mean patient age was 67.0 years, disease duration was 16.2 years, and duration of ABT treatment was 1.2 years at the initiation of add-on TAC therapy. Mean TAC dose was 1.2 mg/d at baseline and 1.6 mg/d at week 24. Mean Disease Activity Score of 28 joints - erythrocyte sedimentation rate was significantly improved at week 24 (3.35) relative to baseline (4.97). The proportion of patients who achieved low disease activity or remission was 40.0%, and the European League Against Rheumatism moderate or good response was 72.0%. ABT retention rate was 92.0% at week 24, as calculated by Kaplan-Meier analysis. Only one patient discontinued add-on TAC therapy due to an adverse event (itching sensation). | This is the first report describing the efficacy and safety profile of add-on TAC therapy with a focus on RA patients with inadequate response to ABT. Our findings suggest that add-on TAC therapy is a worthwhile complementary treatment option in daily clinical practice. |
3,579 | 14,712 | There is no existing comprehensive report on the cellular composition of synovial fluids (SFs) from knee osteoarthritis (OA). We therefore aimed to characterise the immune cell composition in SFs from knee OA (KOA) and in subgroups according to gender.
The immunophenotyping of monocyte/macrophage lineage cells, T and B cells, NK cells, neutrophils, dendritic and mast cells (MC) present in SFs from 53 patients (24 males/29 females) with KOA was performed using 6-colour flow cytometry.
SFs from patients with OA contained 90% hematopoietic cells. Lymphocytes were the predominant cell population (44.8%) in the SFs of OA patients, with CD4 | Based on the immune cell composition of SFs, data mining analysis revealed distinct phenotypes (monocyte- and lymphocyte-predominant) within each gender group. This first study on the cellular complexity of SFs in KOA showed marked differences between male and female patients. The findings give a rational starting point for patient stratification according to their phenotypes, as is required for phenotype-specific treatment strategies. |
3,580 | 3,526 | Phlomis umbrosa Turczaninow root has been traditionally used to treat fractures, rheumatoid arthritis, and arthralgia. However, the effects and mechanisms of P. umbrosa on osteoarthritis (OA) remain poorly understood and a functional genomic approach has not been investigated.
The purpose of this study was to investigate the effects and mechanisms of P. umbrosa extract (PUE) on OA using transcriptomic analysis.
We performed joint diameter measurements, micro computed tomography, and histopathological analysis of monosodium iodoacetate (MIA)-induced OA rats treated with PUE (200 mg/kg) for 3 weeks. Gene expression profiling in articular cartilage tissue was then performed using RNA sequencing (RNA-seq) followed by signaling pathway analysis of regulatory genes.
PUE treatment improved OA based on decreased joint diameter, increased joint morphological parameters, and histopathological features. Many genes involved in multiple signal transduction pathway and collagen activation in OA were differentially regulated by PUE. These included genes related to Wnt/β-catenin, OA pathway, and sonic hedgehog signaling activity. Furthermore, PUE treatment downregulated cartilage damage factors (MMP-9, MMP-13, ADAMTs4, and ADMATs5) and upregulated chondrogenesis (COL2A1 and SOX-9) by regulating the transcription factors SOX-9, Ctnnb1, and Epas1. | Based on the results of gene expression profiling, this study highlighted the molecular mechanisms underlying the effects of PUE in MIA-induced OA rats. The findings provide novel insight into the mechanisms by which PUE treatment-induced gene expression changes may influence OA disease progression. Taken together, the results suggest that PUE may be used as a source of therapeutic agents for OA. |
3,581 | 20,902 | To explore the potential use of concentrated growth factor (CGF) in the treatment of temporomandibular joint osteoarthritis (TMJ-OA).
Surgical defects were created bilaterally on the condylar cartilage and bone to induce TMJ-OA in goats. CGF was applied to the right joints (CGF group) and physiologic saline was applied to the left joints (unrepaired group). There was a 1-month period of observation after the operation. These joint specimens were evaluated and compared based on gross appearance and histopathologic observations with hematoxylin and eosin (HE). The histopathologic scores of the condylar cartilage and repaired tissue, including cartilage, bone, and connective tissues, were compared between the 2 groups using SPSS 17.0 software.
The unrepaired condylar surface was uneven, whereas the CGF-repaired condylar surface appeared smoother and was covered by cartilage-like tissue. HE staining of the unrepaired condyle showed exposed subchondral bone covered with rare connective tissue and an inflammatory reaction, whereas the CGF-repaired condyle showed tissue repair and regeneration, with bone regeneration and cartilage and a covering of connective tissue over the operated surface. The histologic score of the CGF group was significantly lower than that of the unrepaired group (P = .0127). The CGF group exhibited a significantly larger area of new cartilage and bone generation than the unrepaired group (P = .008 and P = .002, respectively). | CGF might play an important role in processes of the molecular response to TMJ-OA. It can mediate inflammation, protect the subchondral bone, assist cell proliferation, and induce tissue repair in TMJ-OA. |
3,582 | 23,809 | To systematically summarize the literature on: (i) the course of pain and physical functioning; and (ii) predictors of deterioration of pain and physical functioning in patients with osteoarthritis of the hip.
A literature search was conducted in PubMed, CINAHL, Embase, PsychINFO and SPORTDiscus up to July 2015. Meta-analyses and qualitative data syntheses were performed.
Eleven of the 15 included studies were of high quality. With regard to the course of pain and physical functioning, high heterogeneity was found across studies (I² > 71%) and within study populations (reflected by large standard deviations (SDs) of change scores). Therefore, the course of pain and physical functioning was interpreted to be indistinct. Clinical characteristics (higher comorbidity count and presence of knee osteoarthritis), health behaviour factors (no supervised exercise and physical inactivity) and socio-demographics (lower education) were found to predict deterioration of pain (weak evidence). Higher comorbidity count and lower vitality were found to predict deterioration of physical functioning (strong evidence). For several other predictive factors weak evidence was found (e.g. bilateral hip pain, increase in hip pain (change), bilateral knee pain, presence of knee osteoarthritis). | Because of high heterogeneity across studies and within study populations, no conclusions can be drawn with regard to the course of pain and physical functioning. Several clinical characteristics, health behaviours and psychosocial factors prognosticate deterioration of pain and physical functioning. These findings may guide future research aimed at the identification of subgroups of patients with hip osteoarthritis. |
3,583 | 24,791 | Married persons have, on average, better mental health than nonmarried persons. Among married persons, marital satisfaction is associated with better mental health. Studies on mental health in married and nonmarried persons that consider marital satisfaction have categorized patients as satisfied versus unsatisfied, which reduces statistical power and does not generate clinically useful information on mental health across the satisfaction spectrum. Our objective was to demonstrate a novel regression approach to evaluate mental health in women with systemic sclerosis (SSc), comparing married and unmarried women, accounting for continuously measured marital satisfaction.
Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and marital satisfaction with the Dyadic Adjustment Scale-7. A single multiple linear regression model was used to predict CES-D scores from marital status and, among married women, continuously measured marital satisfaction, controlling for demographic and clinical characteristics.
Of 725 women, 494 (68%) were married or living as married. On average, married women had mean CES-D scores that were 2.0 points (0.19 SDs) lower than unmarried women (P = 0.013). Among married women, a 1.0 SD increase in marital satisfaction was associated with a 2.2 point (0.21 SDs) decrease in CES-D scores (P < 0.001). Married women whose marital satisfaction scores were below the 19th percentile had greater predicted depressive symptoms than unmarried women. Married women's predicted CES-D scores ranged from 6.7 points lower to 6.9 points higher than those of unmarried women, depending on marital satisfaction. | Comparisons of mental health in married and unmarried patients with rheumatic diseases should include continuously measured marital satisfaction. |
3,584 | 31,376 | To describe a case of late-onset deep surgical-site infection (SSI) after posterior lumbar interbody fusion in a patient treated with tocilizumab (TCZ) for rheumatoid arthritis (RA), with emphasis on the clinical symptoms and changes in inflammatory markers such as white blood cell (WBC) count and C-reactive protein (CRP) level.
A 74-year-old woman with 3-year history of RA underwent posterior lumbar interbody fusion at the L4/5/S1 level. After confirmation of no clinical symptom of SSI postoperatively, we decided to use TCZ for the patient after 2 months postoperatively. At 8 months after beginning of TCZ, she suffered from sudden onset of severe low back pain (LBP) with fever (38 °C) 1 day after administration of TCZ. Local tissues around the operative wound showed no sign of redness, warmth, or swelling. Increases in body temperature, WBC count, and CRP level were well suppressed by TCZ. Magnetic resonance imaging performed 2 weeks after onset of LBP revealed deep SSI. After surgical debridement and administration of the sensitive antibiotics, no clinical signs of recurrent spondylitis or osteolysis of vertebral body have been seen for 3 years. | As TCZ strongly suppresses inflammatory reactions, detecting deep SSI based on local and systemic findings and laboratory data is quite difficult. Care must be taken regarding SSI when patients treated with TCZ complain of long-lasting LBP after lumbar surgery. |
3,585 | 26,050 | Cardiomyopathy is among the leading causes of death from systemic sclerosis (SSc). Urokinase-type plasminogen activator receptor (uPAR)-deficient mice have been recently reported to display important histopathological hallmarks of SSc, including dermal fibrosis, reduced dermal capillary density, and pulmonary fibrosis. Here, we investigated whether uPAR-deficient mice could display the histopathological features of SSc-related cardiomyopathy.
Ventricular myocardial specimens from uPAR-deficient and wild-type mice at 12 and 24 weeks of age were analysed by both light microscopy and transmission electron microscopy. Picrosirius red staining and hydroxyproline content of myocardial specimens were quantified. Myofibroblast and microvessel counts were determined by immunofluorescence for α-smooth muscle actin and CD31, respectively. Endothelial cell apoptosis was assessed by a combined TUNEL/CD31 immunofluorescence assay. Expression of uPAR in human SSc and control ventricular myocardial autopsy specimens was determined by immunohistochemistry.
The myocardium of 24-week-old uPAR-deficient mice displayed focal ischaemic lesions with cardiomyocyte hypertrophy, myofibril rarefaction and contraction band necrosis. At 24 weeks of age, interstitial and perivascular collagen deposition and myofibroblast counts were significantly greater in myocardial tissue of uPAR-deficient mice than in wild-type mice. In uPAR-deficient mice, myocardial fibrosis was paralleled by microvascular endothelial cell apoptosis and reduced capillary density. uPAR expression was significantly downregulated in the myocardium of patients with SSc. | Typical histopathological features of SSc-related cardiomyopathy are mimicked by uPAR-deficient mice. The downregulation of uPAR in the myocardium of patients with SSc may suggest similar underlying pathogenetic mechanisms. uPAR-deficient mice could be used as a preclinical model to study the mechanisms and therapeutic approaches of myocardial involvement in SSc. |
3,586 | 9,318 | It is not yet known if unicompartmental knee arthroplasty (UKA) patients are more likely to return to work sooner or have improved ability to work (i.e., workability) than total knee arthroplasty (TKA) patients. The following questions were addressed: patients were assessed to determine: (1) whether they returned to work sooner following UKA compared to TKA; (2) whether UKA patients had better WORQ function scores compared to TKA patients; and (3) if UKA patients have higher workability scores and greater satisfaction regarding workability than TKA patients.
A multicenter retrospective cohort study was performed that included patients at least 2 years after having undergone either UKA or TKA surgery and on the condition that patients had been in work in the 2 years prior to surgery. Time period between stopping work and returning to work was assessed; the WORQ scores (0 = worst-100 = best) and the Work Ability Index (WAI = 0-10) and reported satisfaction with work ability.
UKA patients (n = 157, median 60 years, 51% male) were compared to TKA patients (n = 167, median 60 years, 49% male) (n.s.). Of the 157 UKA patients, 115 (73%) returned to work within 2 years compared to 121 (72%) of TKA patients (n.s.). More UKA patients return to work within 3 months (73% versus 48%) (p < 0.01). WORQ scores improved similarly in both groups. The WAI was also comparable between the groups. Dissatisfaction with workability was comparable (UKA 15% versus TKA 18% (n.s.).
III. | TKA and UKA patients have similar WORQ, WAI, and satisfaction scores. However, in this study population, UKA patients to return to work after surgery significantly sooner than TKA patients, which improves their quality of life and allows them to participate actively in society. This information can help health care providers and patients weigh-up the pros and cons and choose the best treatment and timing for patients in the working population. |
3,587 | 63,493 | To assess the effectiveness of magnetic resonance (MR) imaging for the diagnosis of early-stage rheumatoid arthritis (RA).
Fifty subjects (nine men and 41 women) with polyarthralgia who were suspected of having early-stage RA on the basis of clinical and radiographic findings were selected to undergo gadolinium-enhanced MR imaging of the hands. The MR imaging criterion for the diagnosis of early RA was bilateral enhancement in both wrists and/or the metacarpophalangeal and/or proximal interphalangeal joints. Follow-up continued until a final diagnosis was determined. Two patients left the study before the end of follow-up.
Final diagnoses were established after a mean follow-up of 776 days: rheumatoid arthritis in 26 patients and nonrheumatoid disease in 22. Use of the MR imaging criterion yielded the correct diagnosis in 25 patients with RA and three false-positive results in three patients without RA. As compared with the traditional format and classification tree criteria of the American Rheumatism Association, the MR imaging criterion allowed detection of seven and six additional patients with true RA, respectively. | The introduction of MR imaging into the diagnostic criteria for early RA may contribute to more accurate diagnosis in patients suspected of having RA and thus allow an earlier decision to start proper medication. |
3,588 | 22,978 | To assess whether partial meniscectomy is associated with increased risk of radiographic osteoarthritis (ROA) and worsening cartilage damage in the following year.
We studied 355 knees from the Osteoarthritis Initiative that developed ROA (Kellgren-Lawrence grade ≥ 2), which were matched with control knees. The MR images were assessed using the semi-quantitative MOAKS system. Conditional logistic regression was applied to estimate risk of incident ROA. Logistic regression was used to assess the risk of worsening cartilage damage in knees with partial meniscectomy that developed ROA.
In the group with incident ROA, 4.4 % underwent partial meniscectomy during the year prior to the case-defining visit, compared with none of the knees that did not develop ROA. All (n = 31) knees that had partial meniscectomy and 58.9 % (n = 165) of the knees with prevalent meniscal damage developed ROA (OR = 2.51, 95 % CI [1.73, 3.64]). In knees that developed ROA, partial meniscectomy was associated with an increased risk of worsening cartilage damage (OR = 4.51, 95 % CI [1.53, 13.33]).
• Partial meniscectomy is a controversial treatment option for degenerative meniscal tears. • Partial meniscectomy is strongly associated with incident osteoarthritis within 1 year. • Partial meniscectomy is associated with increased risk of worsening cartilage damage. | The probability of having had partial meniscectomy was higher in knees that developed ROA. When looking only at knees that developed ROA, partial meniscectomy was associated with greater risk of worsening cartilage damage. |
3,589 | 58,414 | The molecular weight (MW) of hyaluronic acid (HA) in joints generally declines in inflammatory arthritis. As inflammation exists in certain temporomandibular disorders (TMD), we measured the MW of HA in synovial fluid (SF) recovered from patients with TMD and compared it with that from normal controls.
Synovial fluid was obtained from patients with TMD (21 TMJs) and normal controls (5 TMJs). The MW of HA was measured using high-performance liquid chromatography (HPLC).
In the controls, the MW of HA in SF exceeded the detection limit, 3000 kDa. In contrast, 19 (90.5%) of 21 SF samples from patients showed a decreased MW of HA. The median MW of HA (1570 kDa) in TMD was significantly lower than that in the controls (P < 0.01). | The MW of HA in SF from patients with TMD is decreased. |
3,590 | 39,813 | The histopathology of Sjogren's syndrome (SS) in the human inner ear correlates with mouse models of autoimmune inner ear disease.
SS is an autoimmune disease in which 25% of patients have sensorineural hearing loss (SNHL). The inner ear histology in a SS mouse model has shown degeneration of the stria vascularis (SV) and immunoglobulin G deposition on the basement membrane of SV blood vessels. Correlation with human temporal bone histopathology has not been addressed.
The histopathology and immunohistochemistry of the inner ear in 4 patients with SS is described and compared with SS mouse models.
The histopathology of the inner ear in 3 patients with SS and SNHL showed severe loss of the intermediate cells of the SV and immunoglobulin G deposition on the basement membrane of SV blood vessels. These results parallel those of known SS mouse models. Additionally, there was shrinkage of the spiral ganglia neurons in 2 patients, whereas vestibular ganglia neurons were preserved. The fourth patient with SS and normal hearing showed only mild SV atrophy. | This is the first study describing the pathologic changes in the inner ear of 4 patients with SS. The 3 SS specimens with SNHL showed pathologic changes in the SV similar to the mouse model of autoimmune inner ear disease. Additionally, we propose that spiral ganglia neurons may be directly affected by SS pathology. These results highlight the importance of correlating the histopathology of human temporal bones with animal models to better understand inner ear disease in future research. |
3,591 | 17,465 | To compare healthcare resource utilization and costs between patients aged 18-64 years with osteoarthritis (OA) and matched controls without OA in a privately insured population.
Patients with OA were selected from de-identified US-based employer claims (Q1:1999-Q3:2011). The index date was defined as the first OA diagnosis indicated by ICD-9-CM codes. One year before and after the index date were defined as the baseline and study periods, respectively. A second OA diagnosis during the study period was also required. Patients with OA were matched one-to-one on age, gender, index date, and minimum length of follow-up to controls without OA. Baseline characteristics and study period resource utilization and costs (2016 USD) were compared between cohorts.
This study identified 199,539 patients with OA (knee: 87,271, hip: 19,953, hand: 15,670, spine: 12,496). The average age was 54 years, and 58% were female. OA patients had higher healthcare resource utilization than matched controls in inpatient, emergency room, and outpatient settings (p < .001 for all). Further, patients with OA had 4-times the excess total medical costs of their matched controls ($14,521 vs $3,629; p < .001). Patients with hip OA had the highest medical costs among all joint locations. Outpatient and pharmacy costs were similar among patients with knee, hip, and hand OA, but higher in patients with spine OA. In sub-group analyses, older patients (45-64 years old) had higher costs.
This sample, obtained using claims data, only includes patients who were actively seeking care for OA and were likely symptomatic. Asymptomatic patients would likely not be captured in this analysis. | Patients with OA incur greater healthcare resource utilization and costs than patients without OA, with substantial variation by joint location. |
3,592 | 13,766 | The Mediterranean diet has been associated with lower mortality and lower risk of cardiovascular diseases and cancer. Although its components have been analysed in several studies, only one study has specifically investigated the association between Mediterranean diet and risk of rheumatoid arthritis (RA), and reported no association.
Data on 1721 patients with incident RA (cases) and 3667 controls, matched on age, gender and residential area, from the Swedish epidemiological investigation of RA (EIRA), a population-based case-control study, were analysed using conditional logistic regression. The Mediterranean diet score, ranging from 0 to 9, was calculated from a 124-item food frequency questionnaire.
In the EIRA study (median age of participants 53 years), 24.1% of the patients and 28.2% of the controls had high adherence to the Mediterranean diet (a score between 6 and 9). After adjustments for body mass index, educational level, physical activity, use of dietary supplements, energy intake, and smoking, high adherence reduced the odds of developing RA by 21% (OR 0.79; 95% CI 0.65-0.96) as compared to low adherence (a score between 0 and 2). The OR was even lower among men (OR 0.49; 95% CI 0.33-0.73), but no significant association was found among women (OR 0.94; 95% CI 0.74-1.18). An association between high diet score and low risk of RA was observed in rheumatoid factor (RF)-positive (OR 0.69; 95% CI 0.54-0.88), but not RF-negative RA (OR 0.96; 95% CI 0.68-1.34), and in RA characterised by presence of antibodies to citrullinated peptides (ACPA), but not in ACPA-negative RA. | In this large population-based case-control study, the Mediterranean diet score was inversely associated with risk of RA. However, an association was only found among men and only in seropositive RA. |
3,593 | 27,799 | Biological therapies against tumor necrosis factor α have revolutionized the treatment of several inflammatory rheumatic diseases. However, 30% of responders will present a clinical failure after having controlled the disease for at least 6 months (secondary clinical failure). Biological therapies may induce an unwanted immune response, which may alter the bioavailability of the drug causing a loss of clinical response.
The objective of this study was to assess the correlation between secondary clinical failure (based on Disease Activity Score in 28 Joints or Bath Ankylosing Spondylitis Disease Activity Index) and the type of mechanism involved in failure (based on drug levels) in patients with inflammatory arthropathies treated with anti-tumor necrosis factor α.
Drug and antidrug antibodies (ADAs) serum levels were determined by enzyme-linked immunosorbent assay immediately before drug administration in patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis who presented secondary clinical failure after at least 6 months of treatment with adalimumab (ADL) or etanercept (ETN).
Thirty-six patients with secondary clinical failure were recruited: 63.88% had rheumatoid arthritis, 22.22% had psoriatic arthritis, and 13.88% had ankylosing spondylitis; 58.33% did not respond to ADL, whereas 41.66% did not to ETN. None of the patients treated with ETN showed either subtherapeutic drugs levels or ADAs (failure due to a primary mechanism) whereas it was found that 23.80% of the patients treated with ADL had subtherapeutic drug levels for reasons attributable to immunogenicity (failure due to a secondary mechanism; P = 0.000048). | We suggest the utility of measuring drug and ADA levels in patients with secondary clinical failure to ADL for a better optimization and rational use, but not in patients who fail to ETN. |
3,594 | 2,618 | While elective primary total hip (THA) and knee (TKA) arthroplasty are effective procedures for addressing the symptoms associated with advanced osteoarthritis, there is evidence to suggest that patient anxiety and depression are linked to poorer outcomes following surgery.
A secondary analysis of prospectively-collected data of people undergoing primary elective THA or TKA for osteoarthritis across 19 hospitals was performed. We assessed outcomes at 1 year post-surgery for people with and without medically treated anxiety and/or depression at the time of surgery (A/D and no-A/D). We used unadjusted and adjusted analyses to compare improvement in Oxford Hip or Knee Scores, the incidences of major post-operative complications, satisfaction and index joint improvement by A/D status.
15.2% (254/1669) of patients were identified with anxiety and/or depression at time of surgery. In the unadjusted analysis, the A/D group had greater mean Oxford score improvement by 2.1 points (95% CI 0.8 to 3.4, p = 0.001), increased major complications (OR 1.39, 95% CI 1.05 to 1.85, p = 0.02), were less likely to report a "much better" global improvement for index joint (OR 0.56, 95% CI 0.38 to 0.83, p = 0.003), and there was no statistically significant difference in the rate of satisfaction with the results of surgery (OR 0.64, 95% CI 0.37 to 1.10, p = 0.10). The adjusted analysis found no significant associations between A/D vs. no-A/D and any of the reported outcomes. | After adjustment for confounding variables, people with anxiety and/or depression pre-operatively, compared to those without, have similar outcomes following hip or knee arthroplasty. |
3,595 | 62,452 | To evaluate ultrasonographic methods, including the Doppler technique, as measures of synovial inflammation in finger joints of patients with rheumatoid arthritis.
Ultrasonography was performed with a high frequency transducer (13 MHz). Evaluation of the sonographic data was conducted by two independent observers and included measurement of synovial area and thickness (grey tone ultrasound), vascularisation (power/colour Doppler), and indices of the intra- and extrasynovial arterial flow (spectral Doppler). The flow pattern was estimated by the indices of pulsatility (PI) and resistance (RI).
The sonographic measurements of joint space were reproducible with intraobserver, intraclass correlation coefficients (ICC) 0.82-0.97 (p<0.0001) and interobserver ICC 0.81 (p<0.0001). The mean (SD) fraction of the synovium vascularised in the patients was 0.15 (0.15). The synovial blood flow was characterised by a diastolic flow-that is, the flow persisting during the diastole. The mean (SD) PI was 1.92 (1.18) and RI 0.70 (0.13). The estimated vascular fraction correlated with the erythrocyte sedimentation rate (ESR) (r(s)=0.53, p=0.03). The relative Pi (rPi), an estimate of an abnormally low resistance to vascularisation, correlated with both ESR (r(s)=-0.557, p<0.05) and Health Assessment Questionnaire score (r(s)=-0.584, p<0.05). After an injection of contrast Levovist the vascular fraction increased, while no difference in PI and RI was observed. | Ultrasonography is a reliable tool for estimating the size of the joint space and the synovial activity measured by the degree of vascularisation and pattern of flow. Ultrasonography may be useful in monitoring the synovial inflammation in rheumatoid arthritis. |
3,596 | 40,345 | To systematically analyse the literature on reported adverse events (AEs) of intravenous pulse glucocorticoids (GCs) (≥ 250 mg prednisone equivalent) for inflammatory diseases.
A literature search was done using PubMed, Embase, and Cochrane databases. Studies were selected by two reviewers (NAMS and ND). Available data on the prevalence of GC-related AEs in patients with inflammatory diseases were retrieved.
In only 8 studies (344 patients), 4 placebo-controlled and 4 not placebo-controlled studies, intravenous pulse GC-related AEs had been documented (in total 323 AEs), with an AE rate of 35/100 patient-years. In the 4 placebo-controlled studies among RA and systemic sclerosis patients, most of the odds ratios of individual AEs were not statistically significant, except for flushing, heart rhythm disorder, disturbance of taste, lower respiratory infection, and headache. In the 4 not placebo-controlled studies increased diastolic blood pressure was most frequent, followed by flushing and diabetes mellitus. Adverse events seen in more than 15% of patients of all included studies were increased blood pressure, flushing, headache, disturbance of taste, tachycardia and hyperglycemia. | GC pulse therapy results in a high AE rate, i.e. 35/100 patient-years. Cardiovascular AEs are most frequently reported in the literature. Furthermore, flushing had the highest odds ratio in the placebo-controlled studies and also a high event rate in the not placebo-controlled studies. |
3,597 | 40,896 | The importance of β(2)-glycoprotein I (β(2)GPI)-specific CD4(+) T cells in the development of pathogenic processes in patients with antiphospholipid syndrome (APS) and APS mouse models is well established. Therefore, our objective is to manipulate the β2GPI specific CD4(+) T cells using tolerogenic dendritic cells (tDCs) to induce tolerance. We aim to evaluate the capability of tDCs to induce antigen-specific tolerance in effector/memory T cells from patients with APS and to elucidate the involved mechanism.
DCs and tDCs were produced from patients with APS peripheral-blood-monocytes, using specific cytokines. β(2)GPI-specific tolerance induction was investigated by coculturing control DC (cDC) or tDC, β(2)GPI-loaded, with autologous effector/memory T cells, evaluating the proliferative response, phenotype, cytokines secretion, viability and regulatory T cells.
Human monocyte-derived DCs treated with interleukin (IL)-10 and transforming growth factor β-1 (10/TGF-DC) induced β(2)GPI-specific-unresponsiveness in effector/memory CD4(+) T cells (46.5% ± 26.0 less proliferation) in 16 of 20 analysed patients with APS, without affecting the proliferative response to an unrelated candidin. In five analysed patients, 10/TGF-DC-stimulated T cells acquired an IL-2(low)interferon γ(low)IL-10(high) cytokine profile, with just a propensity to express higher numbers of Foxp3(+)CTLA-4(+) cells, but with an evident suppressive ability. In four of 10 analysed patients, 10/TGF-DC-stimulated T cell hyporesponsiveness could not be reverted and showed higher percentages of late apoptosis, p<0.02. | The inherent tolerance induction resistance of activated T cells present during the development of autoimmune diseases has delayed the application of tDC as an alternative therapy. This study highlights the 10/TGF-DC feasibility to induce antigen-specific unresponsiveness in autoreactive T cells generated in patients with APS by inducing apoptosis or T cells with regulatory abilities. |
3,598 | 12,449 | The objective was to predict insufficient response to 3 months methotrexate (MTX) in DMARD naïve rheumatoid arthritis patients.
A Multivariable logistic regression model of rheumatoid arthritis patients starting MTX was developed in a derivation cohort with 285 patients starting MTX in a clinical multicentre, stratified single-blinded trial, performed in seven secondary care clinics and a tertiary care clinic. The model was validated in a validation cohort with 102 patients starting MTX at a tertiary care clinic. Outcome was insufficient response (disease activity score (DAS)28 >3.2) after 3 months of MTX treatment. Clinical characteristics, lifestyle variables, genetic and metabolic biomarkers were determined at baseline in both cohorts. These variables were dichotomized and used to construct a multivariable prediction model with backward logistic regression analysis.
The prediction model for insufficient response in the derivation cohort, included: DAS28>5.1, Health Assessment Questionnaire>0.6, current smoking, BMI>25 kg/m2, ABCB1 rs1045642 genotype, ABCC3 rs4793665 genotype, and erythrocyte-folate<750 nmol/L. In the derivation cohort, AUC of ROC curve was 0.80 (95%CI: 0.73-0.86), and 0.80 (95%CI: 0.69-0.91) in the validation cohort. Betas of the prediction model were transformed into total risk score (range 0-8). At cutoff of ≥4, probability for insufficient response was 44%. Sensitivity was 71%, specificity 72%, with positive and negative predictive value of 72% and 71%. | A prognostics prediction model for insufficient response to MTX in 2 prospective RA cohorts by combining genetic, metabolic, clinical and lifestyle variables was developed and validated. This model satisfactorily identified RA patients with high risk of insufficient response to MTX. |
3,599 | 53,183 | Meniscus tears are often presumed to be associated with a traumatic event, but they can also occur as a result of the cartilage degeneration process in osteoarthritis (OA). The aim of this paper is to describe the prevalence and clinical correlates of degenerative meniscus tears in women with knee OA.
The subjects were women screened for a double-blind, sham-exercise controlled clinical trial for women over 40 years of age with OA in at least one knee, according to American College of Rheumatology (ACR) clinical criteria. The presence of meniscus tears was assessed via a 3T Intera (Philips Medical Systems) magnetic resonance image (MRI). Clinical examination included a history of arthritis onset and physical examination of the lower extremities. Physical assessments included body composition, muscle strength, walking endurance, gait velocity, and balance. In addition, pain and disability secondary to OA, physical self-efficacy, depressive symptoms, habitual physical activity level and quality of life were assessed via questionnaires.
Almost three-quarters (73%) of the 41 subjects had a medial, lateral, or bilateral meniscus tear by MRI. Walking endurance and balance performance were significantly impaired in subjects with a degenerative meniscus tear, compared to subjects without tears, despite similar OA duration, symptoms, and disability, body composition, and other clinical characteristics. | Meniscus tears, diagnosed by MRI, are very common in older women with knee OA, particularly in the medial compartment. These incidentally discovered tears are associated with clinically relevant impairments of balance and walking endurance relative to subjects without meniscus tears. The explanation for this association requires further study. |
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