Unnamed: 0
int64 0
10k
| id
int64 0
68.8k
| abstract
stringlengths 17
6.97k
| conclusion
stringlengths 1
3.23k
⌀ |
|---|---|---|---|
3,600 | 67,463 | This study was undertaken to clarify the mechanisms responsible for the generation of anti-52-kd SS-A/Ro autoantibodies and to elucidate why, as has recently been reported, anti-52-kd autoantibodies preferentially recognize the denatured form rather than the native 52-kd molecule.
Using a series of truncated 52-kd autoantigens, produced as beta-galactosidase fusion proteins in Escherichia coli, the B cell epitope distribution was probed with 18 anti-Ro-positive sera by immunoblotting and by enzyme-linked immunosorbent assay.
Nearly all the antigenicity of the molecule was found to be linked to its leucine zipper region. In a further study using 9 of the 18 sera, the antigenicity of the molecule was found to be mainly formed by multiple conformational epitopes, and one of these epitopes appeared to be universally recognized by all the sera tested. | The recognition of multiple epitopes indicates that the Ro 52-kd antigen itself drives the autoimmunity to this molecule. Further, the concentration of the antigenicity at the leucine zipper region may explain why anti-52-kd antibodies preferentially recognize the denatured protein rather than its native form. |
3,601 | 52,447 | To examine the role of hand dual-energy x ray absorptiometry (DEXA) compared with radiography in the assessment of bone involvement in patients with early rheumatoid arthritis (RA) who have active disease.
The study population (n = 79) had RA of <12 months' duration and were selected for poor prognostic features. Clinical data and bone mineral density (BMD) data were collected at baseline, 24 and 48 weeks. Hand radiographs were performed at baseline and 48 weeks. Bone damage analyses were performed for the group and individuals using the smallest detectable change (SDC) method.
At baseline, mean disease duration was 8.5 months, erythrocyte sedimentation rate was 34.3 mm/hour, C-reactive protein was 40.2 mg/l, Health Assessment Questionnaire score was 1.35 and 81% of patients were positive for rheumatoid factor. Mean (95% CI) hand BMD loss was 2.5% (-3.5 to -1.5) at 24 weeks and 2.6% (-3.8 to -1.5) at 48 weeks. Individual hand bone loss exceeding the SDC was seen in 46.8% at 24 weeks and in 58.2% at 48 weeks. In the subgroup of 58 patients who had undergone radiography, radiographic joint damage score evaluated by the Sharp-van der Heijde method increased from 4.8 to 10.6 (p = 0.001). Individual hand bone loss in this subgroup exceeding the SDC was seen in 50.0% at 24 weeks and in 56.9% at 48 weeks, whereas at 48 weeks only 22.4% had deteriorated in modified Sharp score. | The study results indicate that hand DEXA is a more sensitive tool than radiology (radiographic joint-damage scores), for measuring disease-related bone damage in early RA. |
3,602 | 19,638 | This study aimed to evaluate the relationship between circulating adiponectin and visfatin levels and rheumatoid arthritis (RA) and to establish a correlation between serum adipokine levels and RA activity.
We conducted meta-analyses on serum/plasma adiponectin or visfatin levels in patients with RA and controls and correlation coefficients between circulating adiponectin and visfatin levels and Disease Activity Score of 28 joints (DAS28) in RA patients.
Eleven studies comprising 813 RA patients and 684 controls were included in this meta-analysis. The meta-analysis revealed that adiponectin levels were significantly higher in the RA group than in the control group (standardized mean difference [SMD] = 1.529, 95% confidence interval [CI] = 0.354-2.704, P = 0.011). Circulating adiponectin level was not associated with RA activity based on DAS28 and C-reactive protein (CRP) levels. Visfatin levels were significantly higher in the RA group than in the control group (SMD = 2.575, 95% CI: = 0.963-4.189, P = 0.002). A trend of positive correlation among circulating visfatin levels and DAS28 and CRP levels was found (correlation coefficient = 0.416, 95% CI: = -0.917 to 0.795, P = 0.177; correlation coefficient = 0.366, 95% CI: = -0.074 to 0.687, P = 0.101, respectively). | Our meta-analysis demonstrated that circulating adiponectin levels were significantly higher in patients with RA than in controls. Circulating visfatin levels were significantly higher in patients with RA than in controls and a positive correlation between circulating visfatin level and RA activity is suggested. |
3,603 | 67,457 | To describe acute local reactions following intraarticular hylan injection and determine their frequency.
Retrospective review of all patients with osteoarthritis of the knee treated with hylan by 3 rheumatologists.
Twenty-two patients had 88 injections to 28 knees. Six patients had reactions within 24 h of injection characterized by pain, warmth, and swelling, lasting up to 3 weeks. This occurrence was unpredictable. Corticosteroid injections were sometimes required. Synovial fluid cell counts were 5.0-75.0 x 10(9)/l, often with a prominent mononuclear component. Crystal studies and cultures were negative. Radiographic chondrocalcinosis was present in only 1 patient. One patient had serum antibodies to chicken serum proteins. | Intraarticular hylan was associated with significant local inflammatory reactions in 27% of patients, or 11% of injections. The mechanism(s) and long term sequelae are unclear. |
3,604 | 41,737 | In patients with systemic lupus erythematosus (SLE), to determine 1) the prevalence and clinical features of peripheral neuropathies (PN) and whether they were SLE related, 2) whether there are associations between other SLE features and PN.
Patients who met the American College of Rheumatology case definition criteria for SLE peripheral neuropsychiatric syndromes were selected from the University of Toronto Lupus Clinic database. Demographic data and SLE-related clinical and laboratory data were extracted. Health-related quality of life was assessed using the mental and physical component summary score of the SF-36 questionnaire. In a nested case-control study, SLE patients with PN were matched by disease duration and compared with those without PN.
Of 1533 patients in the database, 207 (14%) had PN. Of these, 40% were non-SLE-related. Polyneuropathy was diagnosed in 56%, mononeuritis multiplex in 9%, cranial neuropathy in 13%, and mononeuropathy in 11% of patients. Asymmetric presentation was most common (59%) and distal weakness occurred in 34%. Electrophysiologic studies indicated axonal neuropathy in 70% and signs of demyelination in 20% of patients. Compared with patients without PN, those with PN had significantly more central nervous system involvement, higher SLE-disease activity index 2000 and lower SF-36-PCS. | The prevalence of PN is relatively high in SLE and occurs more frequently in patients with central nervous system involvement and high SLE-disease activity index. There is a predilection for asymmetric and lower extremities involvement, especially peroneal and sural nerves. This manifestation of the disease has a significant impact on the patient's quality of life. |
3,605 | 14,958 | To assess the association between smoking, anti-cyclic citrullinated peptide (anti-CCP) antibody status, and clinical efficacy of biological therapies in rheumatoid arthritis (RA) patients.
This retrospective clinical practice setting study included 1349 RA patients from the METEOR database (aged >18 years). We collected data on sociodemographics, smoking status (smoker, <10, 10-19, and >20 cigarettes/day; ex-smoker; non-smoker), baseline disease activity parameters and anti-CCP, previous disease-modifying anti-rheumatic drugs (DMARDs), biological therapy, combined therapy (steroids and DMARDs), and follow-up disease activity. Clinical efficacy was assessed by European League Against Rheumatism (EULAR) good/moderate response rates for all aggregated biological therapies, based on both smoking and anti-CCP status.
The non-smoking RA patients were more often female at biological therapy initiation than the ex-smokers and smokers (91.1% vs 60.4% and 67.9%, respectively, p < 0.001), and ex-smokers were older than non-smokers and smokers (mean ± sd 56.5 ± 11.1, 53.5 ± 13.3 and 51.3 ± 11.0 years old, respectively; p < 0.001). In total, 845 (62.6%) were non-smokers, 214 (15.9%) ex-smokers, and 290 (21.5%) smokers [daily cigarettes smoked: 148 (11%) <11; 61 (4.5%) 11-20; and 81 (6%) >20]. Anti CCP-antibody status was similar in both groups. Non-smokers showed higher baseline DAS28 than ex-smokers and smokers (5.0 ± 1.5 vs 4.7 ± 1.4 and 4.7 ± 1.4, respectively; p < 0.001) and used more baseline steroids and DMARDs. A higher EULAR response rate was observed in non-smokers than in ex-smokers and smokers (73% vs 65% and 64.1%, respectively; p = 0.004). Drug survival was higher in non-smokers compared to ex-smokers and smokers [57.7 months (46.4-53.8), 38.6 (30.3-46.8), and 50.1 (41.8-58.4); p < 0.001, respectively]. | In daily clinical practice, non-smokers respond better than smokers to biological therapy, but this does not result in better drug survival. |
3,606 | 16,427 | Fetal exposure to maternal rheumatoid arthritis (RA) might impact the long-term risk of disease in the offspring. We examined a possible association between maternal RA and 15 selected groups of chronic diseases in the offspring.
This nationwide cohort study was based on the Danish health registries and included data on all children born alive in Denmark between January 1, 1989 and December 31, 2013. The cohort comprised 2,106 children born by women with RA (exposed), and 1,378,539 children born by women without RA (unexposed). Cox proportional hazards regression models were used, taking a large range of confounders into consideration, and the hazard ratios (HRs) of child and adolescent diseases were calculated.
In children exposed to maternal RA in utero, the HR of thyroid diseases was 2.19 (95% confidence interval [95% CI] 1.14-4.21), epilepsy 1.61 (95% CI 1.16-2.25), and RA 2.89 (95% CI 2.06-4.05). The HRs for anxiety and personality disorders and chronic lung disease including asthma were in the range of 1.15-1.16, but these were not statistically significant associations. | Our results suggest that in utero exposure to maternal RA is associated with an increased risk of thyroid disease and epilepsy in childhood and adolescence, and in particular an increased risk of RA, compared to children born to mothers without RA. These important findings should encourage pediatricians and general practitioners to have an increased awareness of certain chronic diseases in children exposed to RA in utero. |
3,607 | 31,551 | This meta-analysis investigates the efficacy of tumour necrosis factor α (TNFα) blockers versus placebo for the treatment of ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA).
A systematic literature search was conducted independently by two reviewers. Double-blind randomised controlled trials (RCTs) investigating the efficacy of adalimumab, certolizumab, etanercept, golimumab or infliximab in approved dosages in comparison with placebo were included. The use of concomitant non-steroidal antirheumatic drugs was allowed. The outcome parameters were improvement in disease activity and function measured by the Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI) and ASAS40 response. The effect sizes of the changes in BASDAI/BASFI between TNFα blocker and placebo comparator groups were calculated. Mixed effect models were applied separately for RCTs with AS and nr-axSpA patients and differences between those groups were evaluated in a joint model.
20 studies with data from 3096 patients were included in the analysis: 15 studies with AS patients, four with nr-axSpA patients and one with both. For AS patients, TNFα blockers showed better efficacy than placebo for BASDAI (effect size 1.00), BASFI (effect size 0.67) and ASAS40 response (OR 4.7). For nr-axSpA patients, the differences were smaller (effect sizes 0.73, 0.57; OR 3.6). However, after adjustment for the year of publication as a proxy for disease severity, no differences in the effect sizes between the AS and nr-axSpA trials were observed. | Compared with placebo, TNFα blockers improve disease activity and functional capacity clinically meaningful for both AS and nr-axSpA patients. |
3,608 | 10,539 | The primary objective was to develop and test an artificial neural network (ANN) that learns and predicts length of stay (LOS), inpatient charges, and discharge disposition for total hip arthroplasty. The secondary objective was to create a patient-specific payment model (PSPM) accounting for patient complexity.
Using 15 preoperative variables from 78,335 primary total hip arthroplasty cases for osteoarthritis from the National Inpatient Sample and our institutional database, an ANN was developed to predict LOS, charges, and disposition. Validity metrics included accuracy and area under the curve of the receiver operating characteristic curve. Predictive uncertainty was stratified by All Patient Refined comorbidity cohort to establish the PSPM.
The dynamic model demonstrated "learning" in the first 30 training rounds with areas under the curve of 82.0%, 83.4%, and 79.4% for LOS, charges, and disposition, respectively. The proposed PSPM established a risk increase of 2.5%, 8.9%, and 17.3% for moderate, major, and severe comorbidities, respectively. | The deep learning ANN demonstrated "learning" with good reliability, responsiveness, and validity in its prediction of value-centered outcomes. This model can be applied to implement a PSPM for tiered payments based on the complexity of the case. |
3,609 | 67,616 | To analyze Antonovsky's Sense of Coherence (SOC) Scale, in 828 patients with rheumatoid arthritis (RA) from 15 private rheumatology practices. This scale is designed to evaluate strengths within individuals that allow them to select appropriate strategies to deal with stressors; both the total 29-item (SOC-29) total scale and a 13-item (SOC-13) short form of the 29-item scale were analyzed.
Data were collected through mailed self-report questionnaires as a component of a long-term monitoring program. Internal consistency was evaluated according to Cronbach's alpha. Split-halves reliability was estimated according to the Spearman-Brown prophecy formula. Associations of the SOC-29 and the SOC-13 scale scores with demographic, clinical, and psychological variables were analyzed according to Pearson product moment correlations.
Lower SOC-29 and SOC-13 scale scores were correlated significantly with higher scores for difficulty in performing activities of daily living (ADL), a visual analog pain scale score, global health status, and perceived learned helplessness. The levels of correlation for these variables suggest that each measure represents a construct that differs from the SOC. Lower scale scores were also correlated significantly with fewer years of formal education, adjusted for age, sex, and disease duration. | The SOC-29 and SOC-13 scales are reliable and valid in patients with RA. The SOC scale explained in part variation in clinical status in patients with RA. The SOC-13 provides utility comparable to the SOC-29 in patients with RA. |
3,610 | 1,998 | Involving the end-users of scientific research (patients, carers and clinicians) in setting research priorities is important to formulate research questions that truly make a difference and are in tune with the needs of patients. We therefore aimed to generate a national research agenda for Juvenile Idiopathic Arthritis (JIA) together with patients, their caregivers and healthcare professionals through conducting a nationwide survey among these stakeholders.
The James Lind Alliance method was used, tailored with additional focus groups held to involve younger patients. First, research questions were gathered through an online and hardcopy survey. The received questions that were in scope were summarised and a literature search was performed to verify that questions were unanswered. Questions were ranked in the interim survey, and the final top 10 was chosen during a prioritisation workshop.
Two hundred and seventy-eight respondents submitted 604 questions, of which 519 were in scope. Of these 604 questions, 81 were generated in the focus groups with younger children. The questions were summarised into 53 summary questions. An evidence checking process verified that all questions were unanswered. A total of 303 respondents prioritised the questions in the interim survey. Focus groups with children generated a top 5 of their most important questions. Combining this top 5 with the top 10s of patients, carers, and clinicians led to a top 21. Out of these, the top 10 research priorities were chosen during a final workshop. Research into pain and fatigue, personalised treatment strategies and aetiology were ranked high in the Top 10. | Through this study, the top 10 research priorities for JIA of patients, their caregivers and clinicians were identified to inform researchers and research funders of the research topics that matter most to them. The top priority involves the treatment and mechanisms behind persisting pain and fatigue when the disease is in remission. |
3,611 | 60,566 | To investigate whether the occurrence of pulmonary embolism (PE) and/or deep vein thrombosis (DVT) are influenced by use of a tourniquet or not in the patients who underwent total knee arthroplasty for rheumatoid arthritis (RA).
The patients were randomly divided into a with-tourniquet group (19 patients) and a without-tourniquet group (18 patients). In the first group, snowstorm-like echogenic particles were observed after deflation of the tourniquet in all patients according to the transesophageal echocardiography.
In addition, the PaO(2) level was significantly decreased. Also, one had a PE, and DVT was confirmed in two patients. In the without-tourniquet group, none of these conditions was noted. | These results suggest that the use of a tourniquet will promote the risk of developing postoperative PE and/or DVT after total knee arthroplasty. |
3,612 | 27,330 | To explore the function and mechanism of CCL19 in the pathogenesis of rheumatoid arthritis.
Synovial fibroblasts were collected from 5 cases of rheumatoid arthritis. Peripheral blood mononuclear cells (PBMCs) were obtained from 5 healthy people by Ficoll-Hypaque density gradien centrifugation. The cells were stimulated with IL-1beta, TNF-alpha, IL-17 and other cytokines, and then the expression of CCL19 was detected by RT-PCR. The cells also were treated with different concentration of CCL19, then the expressions of IL-1beta, TNF-alpha were detected by RT-PCR, the expressions of p-ERK, p-p38 were detected by western blot.
IL-1beta promoted the CCL19/CCR7 expression in both synovial fibroblasts and PBMCs. CCL19 upregulated the expression of IL-10 in both synovial fibroblasts and PBMCs. The stimulation of CCL19 also increased its receptor CCR7 expression. CCL19 activated p-ERK and p-p38 in PBMCs. | The positive feedback loop between CCL19 and IL-1 participate in the development of rheumatoid arthritis. |
3,613 | 43,827 | To evaluate impact of persistence on therapy on sustained major patient-, physician- and laboratory-reported outcomes (PROs, PHYROs and LAROs, respectively) in 112 recent-onset rheumatoid arthritis (RA) patients.
At each visit a rheumatologist interviewed patients regarding therapy, morning stiffness and fatigue, scored the 28-joint disease activity score and a visual analogue scale (VAS) and determined acute-phase-reactants. The patients completed the Hispanic version of the Rheumatoid Arthritis Disease Activity Index, the Medical Outcome Short Form 36 (SF-36), the Health Assessment Questionnaire (HAQ), a pain-VAS and an overall-disease activity-VAS. Persistence was defined by self-report through directed interview. Sustained major PROs, PHYROs and LAROs were defined according to cut-offs, when maintained for ≥6 months and until last follow-up. Descriptive statistics, Kaplan-Meier curves and Cox models were used.
Total person-time of receiving therapy was of 375.5 patient-years. From February 2004 to June 2009, 36 (32.1%) patients were persistent. Baseline PROs/PHYROs/LAROs showed active disease and poor health status in both groups, but persistent patients (PP) had significantly lower HAQ (p=0.03) and overall-disease activity-VAS (p=0.01). More PP reached a sustained major SF-36-physical function-score (p=0.02). Persistence was the greatest independent risk factor for sustained major PROs (but absence of fatigue) and PHYROs, (p≤0.04). Time from baseline to major and sustained PROs (excluded absence of fatigue), PHYROs and C-reactive protein were shorter in PP (p≤0.04). | Persistence was a strong predictor for major and sustained outcomes in early RA. Favourable outcomes appear earlier in persistent than in non-persistent patients. |
3,614 | 7,173 | Previous investigations showed inconsistent results for associations between vitamin D and knee osteoarthritis (OA). The present study aimed to make a systematic review and meta-analysis for the association between vitamin D and knee OA.
We systematically searched for articles published in the databases PubMed, Web of Science, EMBASE, Medline, and Google Scholar through July 2019. All statistical analyses were made using STATA 12.0 software. The Q test and I
The study indicated that there were no significant associations between serum levels of 25-hydroxy (OH) vitamin D and prevalence, incidence or progression of knee radiographic OA (ROA), and joint space narrowing (JSN). However, a subgroup study showed significant associations of low vitamin D levels with the progression of knee OA. Additionally, the present study showed no significant effect of vitamin D supplementation on knee OA.
Frühere Untersuchungen ergaben inkonsistente Ergebnisse für Assoziationen zwischen Vitamin D und Knie-Osteoarthritis (Knie-OA). Die vorliegende Studie zielte auf eine systematische Überprüfung und Metaanalyse des Zusammenhangs zwischen Vitamin D und Knie-OA ab.
Wir haben systematisch nach Artikeln gesucht, die in folgenden Datenbanken (PubMed, Web of Science, EMBASE, Medline und Google Scholar) bis Juli 2019 veröffentlicht wurden. Alle statistischen Analysen wurden mit der Software STATA 12.0 durchgeführt. Der Q-Test und I
Die Studie ergab, dass keine signifikanten Zusammenhänge zwischen dem Serumspiegel von 25-Hydroxy-Vitamin D (25-OH-Vitamin D) und der Prävalenz, Inzidenz oder Progression von radiografischem OA (ROA) und Gelenkspaltverengung (JSN) im Knie bestehen. Eine Subgruppenstudie zeigte jedoch signifikante Assoziationen niedriger Vitamin-D-Spiegel mit dem Fortschreiten der Knie-OA. Zusätzlich zeigte die vorliegende Studie keinen signifikanten Effekt der Vitamin-D-Supplementierung auf die Knie-OA.
Die Ergebnisse belegen nicht, dass Serumspiegel von 25-OH-Vitamin D mit dem Risiko einer Knie-OA assoziiert waren, außer vielleicht mit dem Fortschreiten der Knie-OA. Darüber hinaus hat eine Vitamin-D-Supplementierung möglicherweise keinen klinisch signifikanten Einfluss auf die Schmerzkontrolle oder den Strukturverlauf (Tibiaknorpelvolumen und JSW) bei Patienten mit Knie-OA. Langfristige klinische Studien sind unerlässlich, um die Wirkung der Vitamin-D-Supplementierung auf die Knie-OA zu untersuchen. | The results do not support that serum levels of 25(OH) vitamin D are associated with the risks of knee OA, except perhaps with progression of knee OA. In addition, vitamin D supplementation may not have a clinically significant effect on pain control or structure (tibial cartilage volume and JSW) progression in patients with knee OA. Longer-term clinical trials are essential to explore the effect of vitamin D supplementation on knee OA. |
3,615 | 21,239 | To determine whether differentially methylated CpGs in synovium-derived fibroblast-like synoviocytes (FLS) of patients with rheumatoid arthritis (RA) were also differentially methylated in RA peripheral blood (PB) samples.
For this study, 371 genome-wide DNA methylation profiles were measured using Illumina HumanMethylation450 BeadChips in PB samples from 63 patients with RA and 31 unaffected control subjects, specifically in the cell subsets of CD14+ monocytes, CD19+ B cells, CD4+ memory T cells, and CD4+ naive T cells.
Of 5,532 hypermethylated FLS candidate CpGs, 1,056 were hypermethylated in CD4+ naive T cells from RA PB compared to control PB. In analyses of a second set of CpG candidates based on single-nucleotide polymorphisms from a genome-wide association study of RA, 1 significantly hypermethylated CpG in CD4+ memory T cells and 18 significant CpGs (6 hypomethylated, 12 hypermethylated) in CD4+ naive T cells were found. A prediction score based on the hypermethylated FLS candidates had an area under the curve of 0.73 for association with RA case status, which compared favorably to the association of RA with the HLA-DRB1 shared epitope risk allele and with a validated RA genetic risk score. | FLS-representative DNA methylation signatures derived from the PB may prove to be valuable biomarkers for the risk of RA or for disease status. |
3,616 | 64,877 | To examine the association of HLA-DRB1 alleles with polymyalgia rheumatica (PMR) in a Mediterranean country and to explore the role of HLA-DRB1 genes in determining disease severity.
A five year prospective follow up study of 92 consecutive PMR patients diagnosed by the secondary referral centre of rheumatology of Reggio Emilia, Italy was conducted. HLA-DRB1 alleles were determined in the 92 patients, in 29 DR4 positive rheumatoid arthritis (RA) patients, and in 148 controls from the same geographical area by polymerase chain reaction amplification and oligonucleotide hybridisation.
No significant differences were observed in the frequencies of HLA-DRB1 types and in the expression of HLA-DRB 70-74 shared motif between PMR and controls. The frequency of the patients with double dose of epitope was low and not significantly different in PMR and in controls. No significant differences in the distribution of HLA-DR4 subtypes were observed between DR4+ PMR, DR+ RA, and DR4+ controls. Results of the univariate analysis indicated that an erythrocyte sedimentation rate (ESR) at diagnosis > 72 mm 1st h, the presence of HLA-DR1, DR10, rheumatoid epitope, and the type of rheumatoid epitope were significant risk factors associated with relapse/recurrence. Cox proportional hazards modelling identified two variables that independently increased the risk of relapse/recurrence: ESR at diagnosis > 72 mm 1st h (RR=1.5) and type 2 (encoded by a non-DR4 allele) rheumatoid epitope (RR=2.7). | These data from a Mediterranean country showed no association of rheumatoid epitope with PMR in northern Italian patients. A high ESR at diagnosis and the presence of rheumatoid epitope encoded by a non-DR4 allele are independent valuable markers of disease severity. |
3,617 | 61,444 | This study was undertaken to compare trabecular bone mineral density (BMD) in premenopausal rheumatoid arthritis (RA) patients and normal age-matched controls.
A protocol was designed to record age, duration of disease, use of corticosteroids (CS) and/or slow-acting antirheumatic drug (SAARD) therapy together with duration of such therapy. BMD was measured using the Hologic QDR 1,000 dual energy X-ray absorptiometer. The first four lumbar vertebrae and the left femur were measured in 56 RA patients and 165 controls. Height and weight were measured. Comparisons were made between RA patients and controls, as well as between subgroups of RA patients based on CS therapy.
Patients with RA had significantly lower BMD (P < 0.05) at all the sites than the normal controls. The mean duration of RA at the time of study was 60 months (standard deviation 58 months). Thirteen RA patients had used CS in doses less than 10 mg daily for 6 months or longer (mean 19 months), while 25 patients had been on SAARD for an excess of 6 months (mean 23 months). The CS-treated patients had significantly lower BMD than untreated subjects at the femoral neck and inter-trochanteric region (P < 0.05), but not at the lumbar spine. However, when compared with normal controls, the CS-treated subgroups had significantly lower BMD at the lumbar spine and all femoral areas. Trochanteric BMD was the best determinant of the RA group, with a sensitivity of 65% and specificity of 77%. The positive predictive value was 16%, while the negative predictive value was 10%. Using Bayes' theorem, the prevalence of osteopenia in RA was found to be 6%. | We conclude that generalised bone loss is a systemic feature of RA and that loss at the spine and femur may be aggravated by CS therapy. |
3,618 | 59,505 | The relationship between Osteoarthritis (OA) and Osteoporosis (OP) is not well defined due to lacking in longitudinal data, mainly regarding correlations between biochemical factors and OA incidence. Aim of this paper was to investigate the predictive value for OA incidence of bone mass variations and of selected biochemical markers in healthy women participating in a population-based longitudinal study carried out in Naples (Italy).
High completion rate (85.2%) and statistically adequate sample size were obtained: 139 women (45 to 79 years of age) were examined and follow up visit was performed after two years (24+/-2 months), following the same protocol. Patients underwent medical examination, questionnaire, anthropometric measurements, blood sampling and urine collection. Bone mineral density (BMD) measurement was performed by dual energy X-ray absorptiometry (DEXA) at the lumbar spine (L1-L4) and femoral neck. Radiographs of dorsal and lumbar spine in lateral view were performed at basal and at 24 months visits; a team of three experts scored radiographs using Kellgren and Lawrence grading.
The score was calculated for two individual radiographic features (narrowing of the joint space, presence of osteophytes) and as a global score. Results show a relevant percentage, 23% up, of subjects presenting both OA and OP. In the cross-sectional study the presence of osteophytosis correlates with anthropometric variables and PTH levels. In the longitudinal study results show a correlation between serum vitamin D and delta score for osteophytosis (beta=0.02 p<0.05). | Data obtained outline the importance of further studies on the pathogenetic link between OA and bone metabolism. |
3,619 | 14,674 | Prevalence of anxiety and depression is high in people with Primary Sjögren's syndrome (pSS). However, there are currently no known reported studies about anxiety/depression in pSS patients from China. Our aim was to compare anxiety/depression in pSS patients and healthy controls; to investigate the prevalence of anxiety and/or depression among pSS patients in China; to evaluate its relationship with the disease activity, fatigue, pain, education, ocular surface disease, oral health, swallowing disorders, employment status, European League Against Rheumatism Sjögren's Syndrome Patient Reported Index(ESSPRI) as well as to analyze potential determinants of anxiety and depression.
In this study, 160 pSS patients and 170 age- and sex- matched healthy controls were included. Participants completed self-administered questionnaires, Hospital Anxiety and Depression Scale (HADS) and so on. Independent samples t-tests, χ
We found 33.8% pSS patients were anxiety, and 36.9% had depression, which were significantly higher than controls. And there were significant correlations among education, employment status, disease activity, fatigue, ocular surface disease, ESSPRI, oral health, swallowing disorders and anxiety/depression. Meanwhile, logistic regression analysis revealed that oral health and swallowing disorders were significantly associated with anxiety in pSS patients; as well as fatigue was significantly associated with depression. | The prevalence of depression and anxiety was high in adult pSS patients. Interestingly, oral health and swallowing disorders were the most important predictors of anxiety in pSS patients. Therefore, rheumatologists should pay attention to the potential mental comorbidities while managing patients with pSS and provide the basis for mental health providers in order to identify effective strategies for preventing and treating depression and anxiety among adult pSS patients. Simultaneously, rheumatologists should also focus on the oral health and swallowing disorders in pSS patients. |
3,620 | 38,299 | We aimed to determine the prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies in a large group of Korean patients with Behçet's disease (BD), with and without joint involvement, and to compare these findings with the prevalences of anti-CCP antibodies in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).
We tested 189 patients with BD, 105 with RA, and 36 with SLE for anti-CCP antibodies and IgM rheumatoid factor in serum. We reviewed the medical records of patients with BD to investigate their personal and clinical characteristics as well as their laboratory test results.
Anti-CCP antibodies were detected in seven of the 189 BD patients (3.7%), at a mean titer of 30.6±44.4 U/mL, in 86 of the 105 RA patients (81.9%) with a mean titer of 198.8±205.7 U/mL, and in nine of the 36 SLE patients (25%) with a mean titer of 180.4±113.9 U/mL. One of the seven anti-CCP-positive BD patients fulfilled the diagnostic criteria for both BD and RA. Five of the seven anti-CCP-positive BD patients (71.4%) had polyarticular joint involvement, and the other two patients (28.6%) had oligoarticular involvement. | We determined the prevalence of anti-CCP antibodies in a large group of Korean BD patients with and without joint involvement. Negative anti-CCP test in patients with BD may help to differentiate BD from RA and SLE, all of which present with similar clinical features. |
3,621 | 27,943 | The current study was designed to test the hypothesis that the fibromyalgia survey criteria would be directly associated with increased opioid consumption after hysterectomy even when accounting for other factors previously described as being predictive for acute postoperative pain.
Two hundred eight adult patients undergoing hysterectomy between October 2011 and December 2013 were phenotyped preoperatively with the use of validated self-reported questionnaires including the 2011 fibromyalgia survey criteria, measures of pain severity and descriptors, psychological measures, preoperative opioid use, and health information. The primary outcome was the total postoperative opioid consumption converted to oral morphine equivalents.
Higher fibromyalgia survey scores were significantly associated with worse preoperative pain characteristics, including higher pain severity, more neuropathic pain, greater psychological distress, and more preoperative opioid use. In a multivariate linear regression model, the fibromyalgia survey score was independently associated with increased postoperative opioid consumption, with an increase of 7-mg oral morphine equivalents for every 1-point increase on the 31-point measure (Estimate, 7.0; Standard Error, 1.7; P < 0.0001). In addition to the fibromyalgia survey score, multivariate analysis showed that more severe medical comorbidity, catastrophizing, laparotomy surgical approach, and preoperative opioid use were also predictive of increased postoperative opioid consumption. | As was previously demonstrated in a total knee and hip arthroplasty cohort, this study demonstrated that increased fibromyalgia survey scores were predictive of postoperative opioid consumption in the posthysterectomy surgical population during their hospital stay. By demonstrating the generalizability in a second surgical cohort, these data suggest that patients with fibromyalgia-like characteristics may require a tailored perioperative analgesic regimen. |
3,622 | 67,249 | We compared gouty diathesis with uric acid versus calcium stones.
We retrospectively reviewed clinical and laboratory data from 95 gouty diathesis patients (28 with uric acid and 67 with calcium stones) and 99 normal subjects.
Of the gouty diathesis patients gouty arthritis was present in 21% of those with uric acid and 12% of those with calcium stones. Hyperuricemia developed in 43% of those with uric acid and 27% of those with calcium stones, and 2% of controls. Urinary pH was independent of the net gastrointestinal absorption of alkali in the gouty diathesis groups. Urinary pH and citrate increased after potassium citrate treatment. | The characteristic features of primary gout were present in both gouty diathesis groups and both are responsive to treatment. |
3,623 | 62,677 | We examined the temporal changes in the expression of interleukin 1beta (IL-1beta), tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in the rat antigen-induced arthritis (AIA) model and investigated how their expression was modulated following disease amelioration by liposomally conjugated methotrexate (G-MLV).
On the day of arthritis induction (day 0), rats were treated with a single intra-articular injection of G-MLV, methotrexate (MTX), a dose of lipid equivalent to G-MLV (E-LIPO) or saline. On days 3 and 7 after disease induction, animals from each experimental group were killed. Joint tissue was examined histologically and for mRNA expression (IL-6, IL-1beta and TNF-alpha) using semiquantitative reverse transcription-polymerase chain reaction.
There was no significant difference (ANOVA) in knee swelling between MTX-, E-MLV- or saline-treated animals from day 0 to day 7. By day 1, G-MLV significantly reduced knee swelling (1.94+/-0.12 mm; P<0.0001) compared with rats treated with MTX (3.17+/-0.18 mm). G-MLV treatment also significantly inhibited the histological progression of AIA. This reduction in disease severity was accompanied by a reduction in IL-1beta mRNA expression in synovial tissue extracts on day 3 and IL-6 mRNA expression on both day 3 and day 7. | Liposomally conjugated MTX may exert its beneficial effects in experimental arthritis through IL-1beta and IL-6 inhibition. |
3,624 | 41,408 | Mortality in systemic lupus erythematosus (SLE) patients is influenced by an increased occurrence of severe cardiovascular complications. Statins have been proven to protect a wide spectrum of SLE patients from these complications. This study was conducted to determine the possible efficacy of atorvastatin in SLE patients as assessed by multi-detector computed tomography (MDCT)-based coronary calcium scoring and single photon emission computed tomography (SPECT) of the myocardium.
Sixty SLE patients in stable clinical conditions were randomized to receive either atorvastatin (40 mg daily; n = 28) or placebo (n = 32). Clinical and biochemical evaluation together with MDCT-based coronary calcium scoring and SPECT studies (Tc-99 m sestamibi) were performed at the time of randomization and after 1 year of treatment.
At randomization, SPECT revealed perfusion defects at rest in 22 (36.7%) patients and exercise-induced defects in 8 (13.3%), whereas MDCT revealed coronary calcifications in 15 subjects (25%). Coronary calcium deposits increased after 1 year in the placebo group (plaque volume change from 35.2 ± 44.9 to 62.9 ± 72.4, P < 0.05; calcium score from 32.1 ± 39.1 to 59.5 ± 64.4; P < 0.05), but not in the atorvastatin group (plaque volume 54.5 ± 62.4 vs. 51.0 ± 47.6, P not significant; calcium score 44.8 ± 50.6 vs. 54.9 ± 62.5, P not significant). The atorvastatin group showed a decrease in total serum cholesterol (from 5.1 ± 1.2 to 4.4 ± 0.7 mmol/L, P < 0.05), LDL cholesterol (2.9 ± 1.0 to 2.3 ± 0.6 mmol/L, P < 0.05), triglycerides (1.6 ± 0.6 to 1.2 ± 0.5 mmol/L, P < 0.05), and C-reactive protein (CRP) (4.4 ± 4.1 to 2.7 ± 1.7 mg/L, P < 0.05). There was no change in the mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score in patients from both groups. Perfusion defects observed at randomization showed no change after one year treatment with atorvastatin. | In SLE patients 40 mg of atorvastatin daily for 1 year led to a decrease in serum lipids and CRP levels. Additionally the progression of atherosclerosis, as assessed by MDCT-based coronary calcium scoring, is restrained by atorvastatin treatment. The value of statin treatment in patients with SLE free from cardiovascular disease clinical symptoms should be addressed in large, prospective clinical trials. |
3,625 | 38,345 | Rheumatoid arthritis(RA) is a debilitating condition.Early diagnosis of RA can be difficult as the disease may initially be indistinguishable from Undifferentiated arthritis(UA). American College of Rheumatology criteria(ACR)is not suitable for early diagnosis as its characteristics are fulfilled when bone damage has already taken place.Anti-cyclic citrullinated antibodies(Anti-CCP) are highly specific for RA and have been used to confirm early diagnosis.
To determine the prevalence and clinical utility of Anti-CCP antibodies in patients with rheumatoid and undifferentiated arthritis at presentation to KNH medical clinics. Design: A cross-sectional descriptive study.
Kenyatta National Hospital Medical Outpatient Clinics (MOPCs) between the month of October 2008 to February 2009.
A total of 95 patients were recruited.The mean age of the patients studied in the RA and UA was 44.7 and 41.2(p=0.356) respectively. Sixty four patients(64) satisfied ACR criteria.The overall prevalence of Anti-ccp antibodies in the population studied was 47.4%.The prevalence of Anti-ccp antibodies in patients who satisfied the ACR criteria was 62.5%.The prevalence of Rheumatoid Factor (RF) in patients who satisfied the ACR criteria was 50% compared to 9.7% for those who did not(p=0.000). The male to female ratio of subjects studied was 1:11. | Anti-ccp antibodies are more prevalent in this cohort of patients with rheumatoid and undifferentiated arthritis than RF It was also concluded that ACR characteristics correlated well with Anti-ccp and RF. A greater percentage of patients who were RF negative were Anti-ccp positive. |
3,626 | 44,972 | The definition of generalized osteoarthritis in the literature is just as controversial as the discussion about correlations between GOA and Heberden's nodes (HN). Therefore, both questions were investigated in patients with proven heredity in a genealogical study of 931 family members.
In 106 patients with HN and 109 control subjects, 70 joints and spinal segments were investigated with respect to characteristic functional parameters. In addition, 44 joints and spinal segments were investigated radiologically.
GOA affects both the small and large joints as well as the spine. This phenomenon is the more pronounced the more finger joints are affected by Heberden's and Bouchard's nodes. | GOA affects the entire musculoskeletal system. The varying manifestation in individual joints and spinal segments is probably attributable to multifactorial local and systemic factors. In an earlier study, a genetic disposition with a maximum HA prevalence of 30% was identified in the study population. Since HA is considered a genetic marker for GOA, it can be assumed that the same is true of GOA prevalence. |
3,627 | 38,370 | To assess whether there are cis-regulatory polymorphisms that regulate protein tyrosine phosphatase, non-receptor type 22 (PTPN22) expression in rheumatoid arthritis (RA).
RNA was extracted from positively selected CD56+, CD8+, and CD4+ mononuclear cells and the 'residual' cells from 12 RA patients heterozygous for the PTPN22 C1858T single nucleotide polymorphism (SNP) (rs2476601). Relative allelic expression was measured by single base extension (SBE) assay.
There was relative differential allelic expression (DAE ≥ 20%) in eight patients (p < 10(-5)); seven patients demonstrated DAE in more than one cell type; four patients had statistically significant differences between these cell populations (p(corrected) < 0.05). | We have demonstrated significant differences in expression of PTPN22 alleles in RA patients, indicating the probable existence of cis-acting regulatory elements. |
3,628 | 41,195 | To assess whether an increased volume of local anaesthetic injection given with intra-articular steroids improves symptom relief in osteoarthritis of the hip.
One hundred and ten patients with hip osteoarthritis were randomized into two groups (A and B). All patients were given 40 mg triamcinolone and 2 ml bupivicaine, and patients from group B were also given 6 ml of sterile water for injection. Change in WOMAC (Western Ontario and McMaster University Osteoarthritis Index Version 3.1) scores from baseline to 3 months were calculated and assessed for clinical and statistical significance. The patients were assessed for pain at 2 weekly intervals using the Oxford pain chart.
Patients from group B showed some reduction in stiffness (7%) and improved function (3%) compared with group A, and there were more clinical responders in these two categories. However, there was no significant statistical or clinical difference in WOMAC scores between the two groups at 3 months. There was also no statistical difference in pain symptoms between the two groups during the study period, measured at 2 weekly intervals. One hundred and two patients reached the study endpoint; eight patients who had bilateral hip injections were subsequently included in the analysis, and these patients did not alter the findings significantly. | Published total injection volumes used for treating osteoarthritis of the hip with intra-articular steroids vary from 3 to 12 ml. The present study has shown that there is no detriment to using a larger volume of injectate, and recommends that practitioners use total volumes between 3 and 9 ml. |
3,629 | 39,634 | Existing productivity questionnaires do not capture sufficient information to enable the proper valuation of an individual's productivity loss to a society. The purpose of this article is to develop a questionnaire that captures the time lost from work due to a health problem and job and workplace characteristics so that the value of productivity loss to society can be calculated.
First, a questionnaire battery was developed by selecting items from existing productivity questionnaires. Next, items with similar content were identified and duplications were eliminated. Third, the draft questionnaire's feasibility was pretested in a focus group (n = 15). Finally, after appropriate refinements, its applicability was tested in 140 employed patients with rheumatoid arthritis recruited from a cohort in the United Kingdom. Multipliers relating the wage to marginal productivity were also derived using the questionnaire.
The final questionnaire includes items on employment status; absenteeism; presenteeism; unpaid work; and job characteristics, which includes questions on team dynamics, availability of substitutes and their substitutability, time sensitivity, and compensation mechanisms. The importance of incorporating these questions demonstrated that when one employee was absent, or present at work but unable to work at full capacity, the consequent output loss could exceed the output of the employee alone. Multipliers were shown to be greater than one and represented the excess output loss. | The new questionnaire enabled the job and workplace characteristics to be captured so that the actual productivity loss at the societal level attributable to absenteeism and presenteeism could be valued. |
3,630 | 51,485 | To evaluate the clinical efficacy of anti-inflammatory therapy in the management of primary Sjögren syndrome.
Thirty-eight patients with primary Sjögren syndrome were included in this study. The diagnosis of Sjögren syndrome was made on the basis of the classification criteria of the American-European Consensus Group. Fluorescein staining score, rose-bengal staining score, Schirmer test score, tear film breakup time, and functional parameters including ocular surface disease index (OSDI) and visual analog scale (VAS) score were measured at the first visit. Anti-inflammatory therapy included topical corticosteroids, topical autologous serum, and topical cyclosporin A. The clinical efficacy of anti-inflammatory treatment was evaluated in terms of subjective symptoms and objective signs (including Schirmer-1 test, breakup time, rose-bengal score, and fluorescein score).
Patients with Sjögren syndrome had higher rose-bengal scores than patients with non-Sjögren dry eye (P < 0.05). The OSDI score showed better correlation with fluorescein score than with VAS score. Subjective symptoms improved with anti-inflammatory treatment in 70% of patients with primary Sjögren syndrome. Anti-inflammatory treatment provided significant improvement in visual acuity and fluorescein score but did not affect Schirmer score, tear breakup time, or rose-bengal score. | Anti-inflammatory therapy in primary Sjögren syndrome significantly improved subjective symptoms and objective ocular signs; however, we did not find evidence that anti-inflammatory treatment increases tear production in patients with Sjögren syndrome. |
3,631 | 50,609 | To examine the comparative internal and external responsiveness of the generic Medical Outcome Study Short Form-36 Health Survey (SF-36) and disease-specific measures in patients with rheumatoid arthritis (RA).
Data were collected from 280 RA patients starting anti-tumor necrosis factor treatment. A total of 168 patients completed a questionnaire including the SF-36, the Arthritis Impact Measurement Scales 2 (AIMS2), the Health Assessment Questionnaire (HAQ), a visual analog scale for general health (VAS-GH), and an 11-point numerical rating scale for pain (NRS pain) at baseline and after 12 months. Internal responsiveness was evaluated with paired samples t-tests and standardized response means (SRM). External responsiveness was investigated with receiver-operating characteristic statistics and Spearman rank-order correlation coefficients. A health transition item was used as the external indicator of change.
No significant differences in internal and external responsiveness were found between the SF-36 and disease-specific measures within the domains physical function, pain, and psychological function. In the domain social function, the SF-36 was more responsive than the AIMS2. In the domain general health, the SF-36 was less responsive (only internal) than the AIMS2 and VAS-GH. | Our study showed comparable internal and external responsiveness of the SF-36 compared with disease-specific measures (AIMS2, HAQ, NRS pain) in all health domains, except social function and general health domains. The assumption that disease-specific measures are more responsive to detect intervention-related changes over time is not confirmed by our data. |
3,632 | 48,103 | To evaluate plasma amino acid (AA) concentrations in patients affected by fibromyalgia (FM) and to study the relationships between their levels and FM clinical parameters.
20 AAs were assessed in 34 FM patients and in 18 healthy volunteers by means of a modified version of the Waters picotag method.
Significant lower plasma taurine, alanine, tyrosine (Tyr), valine, methionine, phenylalanine and threonine concentrations, and the sum of essential AAs were observed in FM patients vs healthy controls (P<0.05). Tyr CAA' ratio and the sum of AAs competing with tryptophan for brain uptake were significantly reduced in FM (P<0.05). A significant correlation was found between FM clinical parameters and certain AAs. | Our results suggest probable defects of gut malabsorption of certain AAs in FM patients. Moreover, given the reduced Tyr CAA' ratio in FM patients, a possible impairment of the cathecolaminergic system in the FM syndrome may be suggested. |
3,633 | 21,604 | It is widely held that most Baker's cysts resolve after treatment of the intra-articular knee pathology. The present study aimed to evaluate the fate of Baker's cysts and their associated symptoms after total knee arthroplasty (TKA).
In this prospective cohort study, 102 patients with (105 were included, however three were lost to follow-up) an MRI-verified Baker's cyst, primary osteoarthritis and scheduled for TKA were included. Ultrasound was performed to evaluate the existence and the gross size of the cyst before and at one year after TKA. Additionally, associated symptoms of Baker's cyst were recorded pre- and post-operatively.
After one year, a Baker's cyst was still present in 87 patients (85%). There was a significant reduction in associated symptoms arising from the Baker's cyst before (71%) to after surgery (31%). No patients developed a new Baker's cyst associated symptoms. However, of the 72 patients who had reported Baker's cyst associated symptoms pre-operatively, 32 patients (44%) still complained of such symptoms one year after surgery. | Baker's cysts had resolved in only a small number of patients (15%) one year after TKA and symptoms from the cysts persisted in 31%. Cite this article: Bone Joint J 2016;98-B:1185-8. |
3,634 | 62,926 | Indications, results, advantages and disadvantages of the computer-guided femoral preparation in total hip arthroplasty (Robodoc) in our patients are recorded and represented.
41 patients who underwent a computer-guided femoral preparation in total hip arthroplasty (Robodoc) were examined after 1 year on average in a prospective study. The evaluation was made using the Harris Hip Score. The advantages and disadvantages of the Robodoc-assisted surgery are described.
More than 80% of the patients had a good or very good result (> 80 points of Harris Hip Score) 3 month after surgery; after 6 months in 20 of 21 patients a score of more than 85 pts. was calculated. The following complications were noticed: thrombotic embolism (2) with one lethal embolism included, fracture of the greater trochanter using the straight stem (3), aseptic drainage due to hematoma (2). 12 patients noticed a postoperative pain at the distal marking pin location (condylus femoris medialis) for an average of 3 months. | Generally, Robodoc-assisted surgery may be performed in all uncemented total hip arthroplasties. The individual indication should be checked because of the increased effort of surgery, the advantages and disadvantages, and the non-proven better long-term results in comparison to the regular technique. It seems that the Robodoc system provides advantages in post-traumatic arthritis and deformities of the proximal femur (varus and valgus neck) on account of the computer-aided preoperative planning and correct operative realization. |
3,635 | 54,179 | To investigate the morphological characteristics of the axis of rheumatoid arthritis (RA) patients with atlantoaxial instability and to determine, by means of sagittal reconstructed computed tomography (CT), the suitability for atlantoaxial transarticular screw fixation.
Twenty-seven patients, who had undergone reconstructed cervical spine CT scanning preoperatively and posterior atlantoaxial arthrodesis for atlantoaxial instability, were identified from a database for inclusion in this study. The isthmus height and internal height of the lateral mass of the axis were measured using digital imaging software.
The mean isthmus height and internal height of the lateral mass of the axis in RA patients (n=14) were significantly lower than in non-RA patients (n=13) (P<0.01). A high-riding vertebral artery (VA) was present in 54% (15 joints, 9 patients) of the 28 atlantoaxial joints in the RA group and in 12% (3 joints, 2 patients) of the 26 atlantoaxial joints in the non-RA group (P<0.01). | In RA patients, the axis showed more extensive thinning of the isthmus and lateral mass than in non-RA patients. A precise preoperative evaluation of screw trajectory using reconstruction CT imaging may be useful in atlantoaxial transarticular fixation, particularly for RA patients with atlantoaxial instability. |
3,636 | 54,917 | To compare the primary therapist model (PTM), provided by a single rheumatology-trained primary therapist, with the traditional treatment model (TTM), provided by a physical therapy (PT) and/or occupational therapy (OT) generalist, for treating patients with rheumatoid arthritis (RA).
Eligible patients were adults requiring rehabilitation treatment who had not received PT/OT in the past 2 years. Participants were randomized to the PTM or TTM group. The primary outcome was defined as the proportion of clinical responders who experienced a > or =20% improvement in 2 of the following measures from baseline to 6 months: Health Assessment Questionnaire, pain visual analog scale, and Arthritis Community Research and Evaluation Unit RA Knowledge Questionnaire.
Of 144 consenting patients, 33 (10 PTM participants, 23 TTM participants) dropped out without completing any followup assessment, leaving 111 for analysis (63 PTM participants, 48 TTM participants). The majority were women (PTM 87.3%, TTM 79.2%), with a mean age of 54.2 years and 56.8 years for the PTM and TTM groups, respectively. Average disease duration was 10.6 years and 13.2 years for each group, respectively. At 6 months, 44.4% of patients in the PTM group were clinical responders versus 18.8% in the TTM group (chi(2) = 8.09, P = 0.004). | Compared with the TTM, the PTM was associated with better outcomes in patients with RA. The results, however, should be interpreted with caution due to the high dropout rate in the TTM group. |
3,637 | 68,733 | To determine and describe the clinical, radiographic, and toxicity profile in a cohort of rheumatoid arthritis patients receiving weekly oral methotrexate (MTX) over a mean period of 90 months, and to compare and contrast these data with our previous data on this cohort, reported after 53 months.
Prospective, open observational study over a mean treatment period of 90 months (range 79-107 months). Standard clinical and laboratory measures of disease activity were assessed by the same investigator at baseline, 1 month, 3 months, and every 3 months thereafter.
A significant improvement from baseline was maintained in all clinical parameters but the number of tender joints. Toxic reactions were as common in months 54-90 as during the first 53 months. The mean dosage of MTX decreased from 14.6 mg/week at the time of the last report to 11.7 mg/week, while the mean prednisone dosage increased from 1.9 mg/day to 2.1 mg/day. Radiographic scores for erosive disease became statistically significantly different from baseline at year 8, and scores for joint space narrowing differed significantly from baseline at years 5 and 8. Since study entry, 2 patients (6.9%) have experienced MTX pneumonitis. | We conclude that a majority of rheumatoid arthritis patients are able to continue MTX treatment with generally sustained efficacy, for intervals that meaningfully exceed those reported previously. |
3,638 | 63,893 | To investigate bone mineral density (BMD) in men with symptomatic osteoporosis and compare BMD in patients with idiopathic, secondary and corticosteroid associated osteoporosis.
Age, number of vertebral fractures at presentation and BMD were investigated in men presenting to a bone metabolism clinic with idiopathic (n=105; group 1), secondary (n=67; group 2) and corticosteroid osteoporosis (n=48; group 3). BMD was measured in 176 healthy men (controls). Osteoporosis was diagnosed if there was >/=20% vertebral deformity.
Age at peak BMD in controls was 20-29 years at spine (LS-BMD) and femoral neck (FN-BMD). LS-BMD did not change with age but FN-BMD decreased in controls and groups 1 and 2. Mean (SD) age was similar in groups 1 (62.8 (11.5) years, 2 (60.2 (11.0)) years and 3 (62.7 (10.4) years with 45%, 51% and 40% of patients respectively presenting before 60 years. Back pain, present for up to 12 months, was the commonest cause of referral. Vertebral fractures at presentation averaged mean (SD) 2.51 (1.9) in group 1, 2.76 (2.2) in group 2 and 2.48 (1.8) in group 3. LS-BMD Z scores and T scores were more negative in group 1 patients with </=3 vertebral fractures compared with FN-BMD suggesting a greater trabecular bone deficit. LS-BMD Z score in group 1 is -1.71, lower than in population studies. LS T score associated with fracture was about -2.4 in all groups. T8, T12 and L1 were the most frequent levels for fracture. | Men with symptomatic osteoporosis present in middle age, have low BMD with similar T scores irrespective of aetiology and sustain >/= 1 fracture. |
3,639 | 24,926 | A considerable proportion of patients with rheumatoid arthritis (RA) do not have a satisfactory response to biological therapies. We investigated the use of metabolomics approach to identify biomarkers able to anticipate the response to biologics in RA patients.
Due to gender differences in metabolomic profiling, the analysis was restricted to female patients starting etanercept as the first biological treatment and having a minimum of six months' follow-up. Each patient was evaluated by the same rheumatologist before and after six months of treatment. At this time, the clinical response (good, moderate, none) was determined according to the EUropean League Against Rheumatism (EULAR) criteria, based on both erythrocyte sedimentation rate (EULAR-ESR) and C-reactive protein (EULAR-CRP). Sera collected prior and after six months of etanercept were analyzed by 1H-nuclear magnetic resonance (NMR) spectroscopy in combination with multivariate data analysis.
Twenty-seven patients were enrolled: 18 had a good/moderate response and 9 were non responders according to both EULAR-ESR and EULAR-CRP after six months of etanercept. Metabolomic analysis at baseline was able to discriminate good, moderate, and non-responders with a very good predictivity (Q2 = 0.68) and an excellent sensitivity, specificity, and accuracy (100%). In good responders, we found an increase in isoleucine, leucine, valine, alanine, glutamine, tyrosine, and glucose levels and a decrease in 3-hydroxybutyrate levels after six months of treatment with etanercept with respect to baseline. | Our study confirms the potential of metabolomic analysis to predict the response to biological agents. Changes in metabolic profiles during treatment may help elucidate their mechanism of action. |
3,640 | 20,619 | P-gp and BCRP1 are transporter proteins that may confer drug resistance.
To compare P-gp and BCRP1 function in rheumatoid arthritis patients with active and inactive disease and to define their relation with disease activity.
We included 17 active patients paired (age, gender, disease duration) to 17 inactive patients. All had baseline evaluations and 27 had additional six-month follow-up. P-gp and BCRP1 functional activity was measured in peripheral mononuclear cells by flow cytometry. Percentage of lymphocytes able to extrude substrates for P-gp and BCRP1 were recorded in the presence/absence of selective inhibitors. Informed consent was obtained. Descriptive statistics and linear regression model were applied.
Active patients had higher efflux function of both transporters than inactive patients: median (25-75 IQR) P-gp of 7.1% (1.4-29.3) vs. 1.6% (0.7-3.5), p = 0.02 and BCRP1 of 6.2% (1.3-22.4) vs. 1.3% (0.7-2), p = 0.007. At baseline, disease activity was the only predictor of both transporter functions. At follow-up, changes in disease activity correlated with shift in P-gp (r = 0.35, p = 0.07) and BCRP1 (r = 0.33, p=0.09) function. | Patients with active rheumatoid arthritis had a higher efflux function of P-gp and BCRP1 compared to inactive patients. The behavior of P-gp and BCRP1 appeared to be conditioned by disease activity. |
3,641 | 48,713 | To report on the outcome of 15 cases of pregnancies in women treated with anti-TNF drugs during conception or pregnancy
French rheumatologists connecting to the web-site of CRI site: http://www.cri-net.com were asked to fill in a structured questionnaire reporting the outcome of pregnancy in women still treated by a TNF blocker at the time of conception.
Spondylarthropathies (n=8), rheumatoid arthritis (n=4), juvenile idiopathic arthritis (n=2), and psoriatic arthritis (n=1) were treated by infliximab (n=3), adalimumab (n=2), or etanercept (n=10). Miscarriages occurred twice, and elective termination was preferred once. Anti-TNF had been administered during the first, second and third trimester of pregnancy in 12, three and two cases. The 12 babies were in good condition, without apparent malformation or symptoms of neonatal illnesses. | The number of reported cases exceeds 300, but only 29 women were treated during their whole pregnancy. The rate of congenital malformations observed so far might appear reassuring compared to the general population for women exposed only during conception. Conversely, there are too few reports of exposure during pregnancy to allow any conclusion about the safety of TNF blockers, and additional long term follow-up of children would be welcome in order to rule out minor forms of VACTERL association that might have been overlooked at birth. |
3,642 | 35,972 | TKA is one of the most commonly performed procedures in the elderly, yet whether age influences postoperative pain, function, and complication rates is not fully understood for this group. This is because the current literature has limited followup, small sample sizes, and no comparator group.
We therefore asked if increasing age adversely affects postoperative pain, Knee Society Scores(©), and complication rates.
We retrospectively reviewed all 438 patients 80 years or older who underwent primary TKA between 1995 and 2005. We established a comparator group of 2754 patients younger than 80 years. We assessed pain, the Knee Society Score(©) (KSS), and the Knee Society Function Score(©) (KSFS). The number and type of complications were recorded and those graded 2 or more using the classification of Dindo et al. were analyzed. Minimum followup was 5 years (mean, 6 years; range, 5-15.5 years).
We found no difference in pain scores at 3, 5, and 10 years between the two groups. The KSS was comparable between groups at Year 5, but the KSFS was lower in the octogenarians. Major complications rates were higher in the octogenarian group (19% versus 15%). | When compared with younger patients, octogenarians can expect comparable pain relief and KSS but lower function and more complications. |
3,643 | 16,641 | To examine the feasibility and potential benefits of peer mentoring to improve the disease self-management and quality of life of individuals with systemic lupus erythematosus (SLE).
Peer mentors were trained and paired with up to 3 mentees to receive self-management education and support by telephone over 12 weeks. This study took place at an academic teaching hospital in Charleston, South Carolina. Seven quads consisting of 1 peer mentor and 3 mentees were matched, based on factors such as age, area of residence, and marital and work status. Mentee outcomes of self-management, health-related quality of life, and disease activity were measured using validated tools at baseline, mid-intervention, and post-intervention. Descriptive statistics and effect sizes were calculated to determine clinically important (>0.3) changes from baseline.
Mentees showed trends toward lower disease activity (P = 0.004) and improved health-related quality of life, in the form of decreased anxiety (P = 0.018) and decreased depression (P = 0.057). Other improvements in health-related quality of life were observed with effect sizes >0.3, but did not reach statistical significance. In addition, both mentees and mentors gave very high scores for perceived treatment credibility and service delivery. | The intervention was well received. Training, the peer-mentoring program, and outcome measures were demonstrated to be feasible with modifications. This result provides preliminary support for the efficacy, acceptability, and perceived credibility of a peer-mentoring approach to improve disease self-management and health-related quality of life in African American women with SLE. Peer mentoring may augment current rheumatologic care. |
3,644 | 67,306 | To determine daily production of nitric oxide (NO) measured as urinary nitrate excretion, and the effect of prednisolone in patients with rheumatoid arthritis (RA).
Twenty four hour urinary nitrate was measured by gas chromatography in 10 patients with RA, before and two to four weeks after commencement of prednisolone 0.5 mg/kg body weight, and in 18 healthy controls.
Before the start of prednisolone treatment the urinary nitrate excretion in patients with RA was 2.7-fold greater (p < 0.001) than that in healthy volunteers. After prednisolone it decreased significantly, by 28%, at which time inflammatory activity (as indicated by C reactive protein, erythrocyte sedimentation rate, joint count, and early morning stiffness) was also reduced considerably. Despite this decrease, the urinary nitrate excretion in patients with RA remained twice that in the control group (p < 0.05). | Our data suggest that the endogenous production of NO is enhanced in patients with RA. Furthermore, the results indicate that, in parallel with suppression of inflammation, this increased NO synthesis could be reduced by prednisolone treatment. |
3,645 | 53,610 | Frequency of occurrence of mycotic infections of the oral mucosa is higher in later years. It is connected with common use of antibiotics, intensive cancer treatment (cytostatics, radiation therapy) as well as immunosuppressant drugs and antibiotics, which have an influence on mikroflora disorders of the oral cavity. Candidiasis of oral mucosa occurs in old patients, in people suffering from diabetes mellitus, hypothyreosis, sideropenia, hypovitaminosis and xerostomia, which is often caused by hypofunction of salivary glands during autoimmune diseases and/or drug and systemic treatment. The aim of the study was to make a retrospective evaluation of frequency of occurring mycotic infections in patients treated in the Department of Periodontology and Oral Mucosa Diseases, Medical University of Gdansk in the 2003, as well as recognition of systemic conditioning of these disorders. The Study material was clinical documentation of 4172 patients, treated because of different oral mucose and periodontium disorders. From these patients, selected was a group of 105 (83 women and 22 men) with diagnosis--Candidosis mucosae oris. Clinical and mycotic examination was performed.
Mycotic infections were found in 105 patients (2.5%). Systemic diseases (74.3%) were found in a maturity of the patients, which indicated systemic predispositions to candida infections. | A wide cooperation between general practitioners and dentists, especially perio-dontologists, is necessary to give full care to patients. Early diagnosis of disorders of the oral cavity of patients with systemic diseases and dentistry treatment or taking preventive measures seems to be necessary. |
3,646 | 40,319 | Uses of synthetic vitamin A derivatives (e.g., isotretinoin used for severe acne) and high doses of preformed vitamin A have been implicated in the pathogenesis of hyperuricemia and gout, whereas a trial reported that β-carotene may lower serum uric acid (UA) levels. We evaluated the potential population impact of these factors on serum UA in a nationally representative sample of US adults.
Using data from 14,349 participants ages ≥20 years in the Third National Health and Nutrition Examination Survey (1988-1994), we examined the relationship between serum retinol, β-carotene, and UA levels using weighted linear regression. Additionally, we examined the relationship with hyperuricemia using weighted logistic regression.
Serum UA levels increased linearly with increasing serum retinol levels, whereas serum UA levels decreased with increasing serum β-carotene levels. After adjusting for age, sex, dietary factors, and other potential confounders, the serum UA level differences from the bottom (referent) to the top quintiles of serum retinol levels were 0, 0.16, 0.32, 0.43, and 0.71 mg/dl (P for trend <0.001), and for β-carotene were 0, -0.15, -0.29, -0.27, and -0.40 mg/dl (P for trend <0.001), respectively. Similarly, the multivariate odds ratios of hyperuricemia from the bottom (referent) to top quintiles of serum retinol levels were 1.00, 1.30, 1.83, 2.09, and 3.22 (P for trend <0.001) and for β-carotene were 1.00, 0.85, 0.68, 0.73, and 0.54 (P for trend <0.001), respectively. The graded associations persisted across subgroups according to cross-classification by both serum retinol and β-carotene levels. | These nationally representative data raise concerns that vitamin A supplementation and food fortification may contribute to the high frequency of hyperuricemia in the US population, whereas β-carotene intake may be beneficial against hyperuricemia. The use of β-carotene as a novel preventive treatment for gout deserves further investigation. |
3,647 | 50,519 | To determine if the amounts of collagen IX mRNA and protein are higher in osteoarthritic cartilage from weight-bearing areas of the knee joint compared to non-weight bearing areas in patients with stage IV osteoarthritis (OA).
Normal and OA cartilage samples were obtained from 15 patients undergoing total knee replacement or necropsies. mRNA was measured by real time RT-PCR and proteins were detected by Western blot and localized at the light and ultrastructural level.
Collagen IX was found throughout all cartilage layers in healthy and OA tissue. Cells deposited collagen IX in the pericellular and interterritorial matrix and a 66% higher amount of collagen IX was detected in the pericellular matrix of the weight-bearing areas adjacent to the main defect in comparison to the macroscopically intact areas. This is in line with a 3.72 times higher amount of the respective mRNA. | The increased levels of collagen IX protein and its mRNAs found in the weight-bearing areas adjacent to the main cartilage defect might reflect an attempt on the part of the diseased cartilage tissue to stabilize and protect the remaining matrix of late-stage osteoarthritic cartilage from further destruction. |
3,648 | 5,733 | To study incidence, time trends, and outcomes of serious infections in systemic sclerosis (SSc).
We used the 1998-2016 US National Inpatient Sample data. We examined the epidemiology, time trends, and outcomes of five serious infections (opportunistic infections (OI), skin and soft tissue infections (SSTI), urinary tract infection (UTI), pneumonia, and sepsis/bacteremia) in hospitalized people with SSc. We performed multivariable-adjusted logistic regression analyses to analyze independent association of factors with healthcare utilization (hospital charges, length of hospital stay, discharge to non-home setting) and in-hospital mortality.
There were 49,904,955 hospitalizations with serious infections in people without SSc and 61,615 in those with SSc. During 1998-2016, the most common serious infections in SSc were pneumonia (45%), sepsis (32%), SSTI (19%), UTI (3%), and OI (3%). In 2013-2014, sepsis surpassed pneumonia as the most common serious infection; by 2015-2016, sepsis was 1.8 times more common than pneumonia. Over the study period, hospital charges increased, while length of hospital stay and in-hospital mortality decreased, overall and for each serious infection. Multivariable-adjusted analyses showed that sepsis, age ≥ 80 years, and Deyo-Charlson score ≥ 2 were associated with significantly higher odds of healthcare utilization and in-hospital mortality, and Medicare or Medicaid insurance payer, Northeast location, urban teaching or non-teaching hospital, and medium or large hospital bed size with significantly higher odds of healthcare utilization. | Outcomes in people with SSc hospitalized with serious infections have improved over time, except higher hospital charges. Identification of factors associated with higher healthcare utilization and in-hospital mortality allows for developing interventions to improve outcomes. |
3,649 | 42,109 | Immunisation against pneumococcus has been shown to reduce pneumonia in rheumatoid arthritis (RA). There is concern that methotrexate may reduce its efficacy. There are very few objective data on the effect of methotrexate on the efficacy of pneumococcal vaccination with pneumovax, and no objective evidence on whether revaccination is necessary in RA patients on methotrexate.
The authors collected information from 180 RA patients on methotrexate relating to their vaccination status and assayed their pneumococcal antibody levels. Data on pulmonary infection were retrieved in the same patients over the preceding decade.
Full data were available for 152 patients, of whom 28 had never been vaccinated against pneumococcus. Median levels were significantly higher in those who had been vaccinated. Unvaccinated patients and those taking oral prednisone were more likely to have had pneumonia in the previous 10 years. The RR for developing pneumonia among non-vaccinated patients was 9.7 (p=0.005) and among steroid-treated patients was 6.5 (p=0.001), after adjusting for age, gender, disease duration and comorbidity. No significant correlation was found between pneumococcal antibody levels and time since vaccination. | This study suggests that a single administration of pneumovax early in RA offers up to 10 years protection against the development of pneumococcal pneumonia in RA patients on methotrexate. |
3,650 | 14,690 | Deficient soft tissue following total knee arthroplasty (TKA) can jeopardize outcome. The gastrocnemius flap is an important means of providing coverage of a knee with deficient soft tissue. There is a paucity of long-term studies on the use of the gastrocnemius flap in the setting of TKA. The purpose of this study was to review the outcomes after the use of pedicled gastrocnemius flaps for coverage of a soft-tissue defect at the time of TKA.
Eighty-three patients in whom a gastrocnemius flap had been used to cover the site of a primary (n = 18) or revision (n = 65) TKA over a 25-year period were identified. There were 48 women (58%) and 35 men (42%) with a mean age and body mass index (BMI) of 65 years and 32.6 kg/m. The mean wound size was 49 cm, and the wound was most commonly located over the anterior aspect of the knee/patellar tendon (n = 33). Patients were followed to the time of implant or flap revision, amputation, or death or for a minimum of 2 years (mean, 8 years). Clinical outcomes were assessed using the Knee Society Score (KSS) for pain and the KSS for function. The Kaplan-Meier method was used to assess revision and amputation-free survival. Risk factors for amputation and revision were identified with Cox regression.
The 10-year revision and amputation-free survival rates following gastrocnemius flap coverage were 68% and 79%, respectively. The risk of implant failure was increased by morbid obesity (BMI of ≥40 kg/m) (hazard ratio [HR] = 2.82, 95% confidence interval [CI] = 1.09 to 7.32, p = 0.03) and ≥5 prior surgical procedures on the knee (HR = 2.68, 95% CI = 1.04 to 6.88, p = 0.04). The risk of amputation was increased in patients with ≥5 prior surgical procedures (HR = 10.76, 95% CI = 2.38 to 48.58, p = 0.002), an age of ≥65 years (HR = 4.94, 95% CI = 1.10 to 22.09, p = 0.03), and a wound size of ≥50 cm (HR = 3.29, 95% CI = 1.14 to 9.53, p = 0.02). Preoperatively the mean KSSs for pain and function were 46 and 28, and these scores significantly (p < 0.05) improved to 78 and 43, respectively, at the time of follow-up.
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. | The gastrocnemius flap reliably provides coverage of components used in complex knee reconstruction. A history of multiple surgical procedures on the knee and larger soft-tissue defects increase the risk of revision TKA and of amputation. |
3,651 | 9,034 | This study was conducted to determine long-term survival rates and the factors associated with mortality in Turkish primary Sjögren syndrome (pSS) patients.
All patients diagnosed with pSS between 2004 and 2014 were included in this study. By January 2019, all subjects still living by the end of the study, as well as any death, were identified. Survival rates and standard mortality rates (SMRs) using general population mortality data were calculated. Mortality-related factors were determined by univariate and multivariate analysis.
During follow-up, 33 cases of 372 pSS patients resulted in death (8.9%). Of those patients, they were typically older at disease onset, at recruitment, and had shorter follow-up times (p < 0.001 for all). The overall SMR of all pSS patients compared with the general population was 2.11 (95% confidence interval (CI) 1.39-2.83). Male pSS patients had a higher SMR than that of general male patients. Overall survival rates were 97.8% at five years, 90.2% at 10 years, and 87.1% at 15 years in patients with pSS. The survival rate of pSS patients was significantly lower than the general Turkish population (p = 0.011). Multivariate Cox regression analysis showed that older age at disease onset and the presence of interstitial lung disease (ILD) were independent risk factors for mortality. | Based on these data, mortality rates of Turkish pSS patients are higher compared with the general population. Survival significantly decreased in the pSS patients with ILD, especially in older male patients at disease onset. Male gender and malignancy may also be associated with a worse prognosis in pSS patients.Key Point• Mortality in Sjögren's syndrome. |
3,652 | 29,949 | The aim of this study was to investigate the outcomes of cement arthroplasty used as a primary salvage procedure to treat ankle joint destruction.
This study included sixteen patients who underwent primary cement arthroplasty from May 2004 to March 2012 because of an ankle disorder, including intractable infection, nonunion, or a large bone defect or tumor. The mean age of the patients was fifty-seven years (range, twenty-three to seventy-four years), and the mean follow-up period was thirty-nine months (range, fourteen to 100 months). The cement spacer position, cement breakage, osteolysis around the inserted cement, and alignment of the joint were evaluated radiographically. American Orthopaedic Foot & Ankle Society (AOFAS) scores and visual analogue scale (VAS) pain scores were recorded preoperatively and at the time of final follow-up. Functional questionnaires were used to assess the duration for which the patient could walk continuously, use of walking aids, sports activity, consumption of pain medication, and the patient's subjective assessment of the percentage of overall improvement compared with before the cement arthroplasty.
The cement spacer was retained without breakage for a mean of thirty-nine months (range, fourteen to 100 months). Osteolysis around the cement was observed in one patient at seventy-eight months, and subluxation developed in one patient. The mean AOFAS and VAS pain scores improved from 39 (range, 11 to 71) preoperatively to 70 (range, 47 to 88) postoperatively (p = 0.001) and from 8 (range, 4 to 9) to 3 (range, 1 to 7) (p = 0.001), respectively. At the final follow-up evaluation, nine of the sixteen patients did not require walking aids, ten used no pain medication, and nine were able to walk continuously for more than an hour. One patient complained of persistent pain and was considered to have had a failure of the procedure.
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. | Primary cement arthroplasty might be a treatment option for advanced ankle destruction in elderly and less active patients. |
3,653 | 55,383 | To investigate the association between biochemical markers of bone, cartilage, and synovial turnover with the presence and severity of knee osteoarthritis (OA) in men.
176 men aged 59-70 years from the MRC Hertfordshire Cohort were studied. Weightbearing anteroposterior and lateral semiflexed radiographs were taken of both knees. A lifestyle questionnaire including basic demographic details and a questionnaire detailing knee pain was completed. This random sample was stratified based on the Kellgren and Lawrence (K&L) score, and the following biochemical markers were analysed: serum osteocalcin, serum C-terminal crosslinked telopeptide of type I collagen (CTX-I), urinary C-terminal crosslinked telopeptide of type II collagen (CTX-II), and urinary glucosyl-galactosyl-pyridinoline (Glc-Gal-Pyd).
Age, body mass index (BMI), social class, smoking, and alcohol consumption were similar across K&L grades. Only one subject had a grade 4 K&L score, and was amalgamated with grade 3 subjects. A strong significant association was found between the presence of knee OA and urinary CTX-II and urinary Glc-Gal-Pyd (p=0.0001 and p=0.009), which persisted after adjustment for age and BMI. A significant positive association was also found between urinary CTX-II and urinary Glc-Gal-Pyd and the severity of K&L grade, joint space narrowing, and osteophytes scores, which persisted after adjustment for age and BMI. No associations between the presence and severity of knee OA were found for serum CTX-I or serum osteocalcin. | Urinary CTX-II and Glc-Gal-Pyd, but not systemic markers of bone turnover, are strongly associated with disease severity and the presence of OA at the tibiofemoral and patellofemoral joints in men. |
3,654 | 48,203 | To uncover the mechanism by which chondroitin sulfate (CS) enhances hyaluronan (HA) production by human osteoarthritic (OA) fibroblast-like synoviocytes (FLS).
The production of HA was investigated by exposing human OA FLS to CS in the presence or absence of interleukin-1beta (IL-1beta). HA levels were determined by enzyme-linked immunosorbent assay, and levels of messenger RNA (mRNA) for HA synthase 1 (HAS-1), HAS-2, and HAS-3 were determined by real-time polymerase chain reaction analysis. The effect of CS and IL-1beta on signaling pathways was assessed by Western blotting. Specific inhibitors were used to determine their effects on both HA production and HAS expression. The molecular size of HA was analyzed by high-pressure liquid chromatography.
CS increased HA production by FLS through up-regulation of the expression of HAS1 and HAS2. This was associated with activation of ERK-1/2, p38, and Akt, although to a lesser extent. Both p38 and Akt were involved in CS-induced HA accumulation. IL-1beta increased HA production and levels of mRNA for HAS1, HAS2, and HAS3. CS enhanced the IL-1beta-induced level of HAS2 mRNA and reduced the level of HAS3 mRNA. IL-1beta-induced activation of p38 and JNK was slightly decreased by CS, whereas that of ERK-1/2 and Akt was enhanced. More high molecular weight HA was found in CS plus IL-1beta-treated FLS than in FLS treated with IL-1beta alone. | CS stimulates the synthesis of high molecular weight HA in OA FLS through up-regulation of HAS1 and HAS2. It reduces the IL-1beta-enhanced transcription of HAS3 and increases the production of HA of large molecular sizes. These effects may be beneficial for maintaining viscosity and antiinflammatory properties in the joint. |
3,655 | 36,146 | Osteoarthritis is the most common joint disease and the leading cause of chronic disability in the U.S. However, symptomatic osteoarthritis at the ankle occurs nine times less frequently than at the knee and hip, even though the ankle experiences greater pressure and is the most commonly injured joint in the human body. This study sought to quantify the shape and coverage of the talar and tibial articular surfaces by comparing the three-dimensional morphology of the ankle in patients with ankle osteoarthritis and in those without arthritis, including a subset of different foot shapes.
We created three-dimensional models of the joint surfaces of ankles with and without arthritis. We fit cylinders to the joint surfaces, and measured the radius of the tibial and talar articular surfaces, the tibial coverage angle of the talus, and the degree of joint skew. We hypothesized that these measurements would be different between those with and without ankle osteoarthritis and among foot types. We evaluated a total of 108 limbs.
The mean tibial and talar radii were significantly higher and the mean coverage angle was significantly lower in feet with ankle osteoarthritis than in all other foot categories. The mean coronal skew in limbs with ankle osteoarthritis was significantly higher than in the neutral and flatfoot groups. The high arched feet had several significantly different skew angles from other foot types. No significant differences in joint morphology measures between neutrally aligned feet and flatfeet were found. | Ankles with osteoarthritis had larger tibial and talar radii, a smaller coverage angle, and larger skew angles than ankles without osteoarthritis. Together, these findings suggest a flatter ankle joint with less stability, depth, and containment and reduced articular constraint and support. |
3,656 | 21,353 | To prospectively evaluate the relationship between the presence or persistence of anterior knee pain (AKP) during the first 2-years following anterior cruciate ligament reconstruction (ACLR) and patellofemoral osteoarthritis (PFOA) at 15- and 20-years.
This study was ancillary to a long-term prospective cohort study of 221 participants following bone-patellar-tendon-bone ACLR. AKP was assessed at 1- and 2-years post-ACLR using part of the Cincinnati knee score with an additional pain location question (persistence defined as presence at both follow-ups). Radiographic PFOA (definite patellofemoral osteophyte) and symptomatic PFOA (patellofemoral osteophyte, with knee pain during past 4 weeks) was assessed at 15- and 20-years follow-up. We used generalized linear models with Poisson regression to assess the relationship between AKP and PFOA.
Of the 181 participants (82%) who were assessed at 15-years post-ACLR (age 39 ± 9 years; 42% female), 36 (24%) and 33 (22%) had AKP at 1- and 2-years, respectively, while 14 (8%) reported persistent AKP. Radiographic and symptomatic PFOA was observed at 15-years in 130 (72%) and 70 (39%) participants, respectively, and at 20-years in 115 (80%) and 60 (42%) participants, respectively. Neither the presence nor persistence of AKP at 1- and/or 2-years post-ACLR was associated with significantly higher risk of radiographic or symptomatic PFOA at 15- or 20-years (risk ratios <2.1). | Although AKP and PFOA were prevalent, AKP does not appear to be associated with long-term PFOA following ACLR. |
3,657 | 44,929 | Childhood susceptibility to diseases linked with immune dysfunction affects over a quarter of the pediatric population in some countries. While this alone is a significant health issue, the actual impact of immune-related diseases extends over a lifetime and involves additional secondary conditions. Some comorbidities are well known (e.g., allergic rhinitis and asthma). However, no systematic approach has been used to identify life-long patterns of immune-based disease where the primary condition arises in childhood. Such information is useful for both disease prevention and treatment approaches.
Recent primary research papers as well as review articles were obtained from PubMed, Chem Abstracts, Biosis and from the personal files of the authors. Search words used were: the diseases and conditions shown Figs. 1 and 2 in conjunction with comorbid, comorbidities, pediatric, childhood, adult, immune, immune dysfunction, allergy, autoimmune, inflammatory, infectious, health risks, environment, risk factors.
Childhood diseases such as asthma, type-1 diabetes, inflammatory bowel disease, respiratory infections /rhinitis, recurrent otitis media, pediatric celiac, juvenile arthritis and Kawasaki disease are examples of significant childhood health problems where immune dysfunction plays a significant role. Each of these pediatric diseases is associated with increased risk of several secondary conditions, many of which appear only later in life. To illustrate, four prototypes of immune-related disease patterns (i.e., allergy, autoimmunity, inflammation and infectious disease) are shown as tools for: 1) enhanced disease prevention; 2) improved management of immune-based pediatric diseases; and 3) better recognition of underlying pediatric immune dysfunction. | Identification of immune-related disease patterns beginning in childhood provides the framework for examining the underlying immune dysfunctions that can contribute to additional diseases in later life. Many pediatric diseases associated with dysfunctional immune responses have been linked with an elevated risk of other diseases or conditions as the child ages. Diseases within a pattern may be interlinked based on underlying immune dysfunctions and/or current therapeutic approaches for managing the entryway diseases. It may be beneficial to consider treatment options for the earliest presenting diseases that will concomitantly reduce the risk of immune-linked secondary conditions. Additionally, improved disease prevention is possible with more relevant and age-specific immune safety testing. |
3,658 | 41,842 | We examined the relationship between antinuclear antibody (ANA) data and the presence of anti-double stranded DNA antibodies (anti-dsDNA).
De-identified demographic, ANA and anti-dsDNA data were available for 30,196 individuals aged ≥ 20 years, whose sera were submitted sequentially to our laboratory. When multiple sera were received for the same subject, data from the earliest sample were used. Anti-dsDNA frequency was stratified by ANA titer and pattern, sample referral source, and by the patient's age, gender, and diagnosis.
For sera with ANA titer ≥ 256 and an accompanying diagnosis of systemic lupus erythematosus, anti-dsDNA frequency was 53.7%, 35.3%, and 37.5% for homogeneous, speckled, or multiple ANA patterns, respectively. Among remaining sera with ANA titer ≥ 256, anti-dsDNA frequency was highest for the homogeneous pattern (15.9%). Anti-dsDNA frequency was three-fold higher among sera submitted by rheumatologists compared with other providers. However, its relative distribution by ANA pattern and titer was similar between these groups. Patient age and gender had no significant effect on anti-dsDNA frequency after ANA data were taken into account. | ANA pattern and titer, together with the diagnosis submitted with the serum sample, can be used to guide decisions for reflexive anti-dsDNA testing in a clinical laboratory setting. |
3,659 | 14,825 | To compare 2-year outcomes of total knee replacement (TKR) followed by non-surgical treatment to that of non-surgical treatment alone and outcomes of the same non-surgical treatment to that of written advice.
In two randomized trials, 200 (mean age 66) adults with moderate to severe knee osteoarthritis (OA), 100 eligible for TKR and 100 not eligible for TKR, were randomized to TKR followed by non-surgical treatment, non-surgical treatment alone, or written advice. Non-surgical treatment consisted of 12 weeks of supervised exercise, education, dietary advice, use of insoles, and pain medication. The primary outcome was the mean score of the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales, covering pain, symptoms, activities of daily living (ADL), and quality of life (QOL).
Patients randomized to TKR had greater improvements than patients randomized to non-surgical treatment alone (difference of 18.3 points (95% CI; 11.3 to 25.3)), who in turn improved more than patients randomized to written advice (difference of 7.0 points (95% CI; 0.4 to 13.5)). Among patients eligible for TKR, 16 (32%) from the non-surgical group underwent TKR during 2 years and among those initially ineligible, seven patients (14%) from the non-surgical group and ten (20%) from the written advice group underwent TKR.
ClinicalTrials.gov numbers NCT01410409 and NCT01535001. | TKR followed by non-surgical treatment is more effective on pain and function than non-surgical treatment alone, which in turn is more effective than written advice. Two out of three patients with moderate to severe knee OA eligible for TKR delayed surgery for at least 2 years following non-surgical treatment. |
3,660 | 68,656 | To reassess synovial intimal cell populations by light microscopy.
Non-inflamed, rheumatoid and osteoarthritic synovia were analyzed as tissue sections and cytospin preparations by a series of combined immunohistochemical and cytochemical staining techniques.
Two populations of intimal cells were identified. The first carried macrophage markers. The second showed high uridine diphosphoglucose dehydrogenase (UDPGD) activity, minimal cytoplasmic CD68, absent non-specific esterase (NSE) activity, and absent leukocyte and endothelial antigens. The majority of these cells showed a high content of prolyl hydroxylase. | Combined cytochemical staining for NSE and UDPGD activity allows effective separation of intimal cell populations. We suggest that the cells of high UDPGD activity are the fibroblast-like or type B synovial intimal cells defined by electron microscopy. High UDPGD activity probably reflects a preferential ability to synthesize glycosaminoglycans, including hyaluronan. |
3,661 | 67,175 | To validate the European League Against Rheumatism (EULAR), the American College of Rheumatology (ACR), and the World Health Organization (WHO)/International League Against Rheumatism (ILAR) response criteria for rheumatoid arthritis (RA).
EULAR response criteria were developed combining change from baseline and level of disease activity attained during follow up. In a trial comparing hydroxychloroquine and sulfasalazine, we studied construct (radiographic progression), criterion (functional capacity), and discriminant validity.
EULAR response criteria had good construct, criterion, and discriminant validity, ACR and WHO/ILAR criteria showed only good criterion validity. | EULAR response criteria showed better construct and discriminant validity than did the ACR and the WHO/ILAR response criteria for RA. |
3,662 | 41,885 | Intercellular adhesion molecule-1 (ICAM-1) is involved in migration and co-stimulation of T and B cells. Membrane bound ICAM-1 is over expressed in the salivary glands (SG) of Sjögren's syndrome (SS) patients and has therefore been proposed as a potential therapeutic target. To test the utility of ICAM-1 as a therapeutic target, we used local gene therapy in Non Obese Diabetic (NOD) mice to express soluble (s)ICAM-1 to compete with membrane bound ICAM-1 for binding with its receptor. Therapy was given prior to and just after the influx of immune cells into the SG.
A recombinant serotype 2 adeno associated virus (rAAV2) encoding ICAM-1/Fc was constructed and its efficacy tested in the female NOD mice after retrograde instillation in SG at eight (early treatment) and ten (late treatment) weeks of age. SG inflammation was evaluated by focus score and immunohistochemical quantification of infiltrating cell types. Serum and SG tissue were analyzed for immunoglobulins (Ig).
Early treatment with ICAM-1/Fc resulted in decreased average number of inflammatory foci without changes in T and B cell composition. In contrast, late treated mice did not show any change in focus scores, but immunohistochemical staining showed an increase in the overall number of CD4+ and CD8+ T cells. Moreover, early treated mice showed decreased IgM within the SGs, whereas late treated mice had increased IgM levels, and on average higher IgG and IgA. | Blocking the ICAM-1/LFA-1 interaction with sICAM-1/Fc may result in worsening of a SS like phenotype when infiltrates have already formed within the SG. As a treatment for human SS, caution should be taken targeting the ICAM-1 axis since most patients are diagnosed when inflammation is clearly present within the SG. |
3,663 | 11,661 | Parotidomegaly is a criterion of the EULAR Primary Sjögren Syndrome Disease Activity Index (ESSDAI). The cut-off value was set at 3 cm in length for the parotid gland, 2 cm for the submandibular glands. However, clinical appreciation of salivary glands size remains hazardous. The objective is to evaluate inter-observer reproducibility of parotid gland measurement by palpation, and to secondary evaluate its reliability compared to US assessment.
Outpatients with primary Sjögren Syndrome (pSS) or with a diagnostic suspicion, in a single reference centre, were included. They underwent clinical examination by two independent investigators (VDP and DC), evaluating: parotid gland swelling, parotid gland size (direct measurement with a decameter under the mandibular angle), and pain. Cohen's kappa coefficient was calculated to determine inter-observer concordance for parotid gland swelling, and intraclass correlation coefficient to determine inter-observer agreement of gland size measurement.
Thirty-four patients (33 women, 1 man) were included. Clinical data were complete for 33 patients. Inter-observer concordance Kappa coefficient was 0.90 [0.76-1.00] for detection of parotidomegaly over 66 parotid glands. It was of 0.60 [0.42-0.73] for gland length measurement. For one observer, the median cut-off for defining parotidomegaly was 4.15 cm; for the second observer, it was of 4.92 cm. For submandibular glands palpation, no correlation was found between investigators. A significant association between clinical parotidomegaly and a larger echographic surface was found. | Clinical measurement of parotidomegaly was concordant between two observers on a binary mode (presence/absence). However, concordance on direct measurement was weak. US could be a complementary examination. |
3,664 | 35,099 | The present study was undertaken to replicate the association of candidate genes for anti-TNF response in rheumatoid arthritis. Candidate genes were selected from a recent genome-wide association study on anti-TNF response performed in a population from Denmark.
Genomic DNA was obtained from 315 Spanish rheumatoid arthritis patients having received an anti-TNF agent as their first biological therapy. SNPs from NR2FR2, MAP2K6, CBLN2 and PDE3A-SLCO1C1 candidate loci were genotyped.
The PDE3A-SLCO1C1 locus rs3794271 SNP showed a highly significant association with anti-TNF treatment response (p = 1.74 × 10⁻⁵). Combining the statistical evidence from the Spanish and Danish rheumatoid arthritis cohorts, the associated rs3794271 SNP reached a genome-wide significance level of association (p = 3.3 × 10⁻¹⁰). | The present findings establish the PDE3A-SLCO1C1 locus as a strong genetic marker of anti-TNF therapy response. |
3,665 | 27,811 | To evaluate the impact of RA on work capacity and identify factors related to work capacity impairment in patients with RA.
A cross-sectional multicentre study was performed in 21 tertiary care hospitals across China. A consecutive sample of 846 patients with RA was recruited, of which 589 patients of working age at disease onset constituted the study population. Information on the socio-demographic, clinical, working and financial conditions of the patients was collected. Logistic regression analyses were used to identify factors associated with work capacity impairment.
The rate of work capacity impairment was 48.0% in RA patients with a mean disease duration of 60 months (interquartile range 14-134 months), including 11.7% leaving the labour force early, 33.6% working reduced hours and 2.7% changing job. Multivariable logistic regression analysis showed that reduced working hours was significantly related to current smoking [odds ratio (OR) 2.07 (95% CI 1.08, 3.97)], no insurance [OR 1.94 (95% CI 1.20, 3.12)], in manual labour [OR 2.66 (95% CI 1.68, 4.20)] and higher HAQ score [OR 2.22 (95% CI 1.36, 3.60)]. There was an association of current smoking [OR 3.75 (95% CI 1.54, 9.15)], in manual labour [OR 2.33 (95% CI 1.17, 4.64)], longer disease duration [OR 1.01 (95% CI 1.00, 1.01)] and lower BMI [OR 0.90 (95% CI 0.82, 0.99)] with leaving the labour force early. | There is a substantial impact of RA on the work capacity of patients in China. Social-demographic, disease- and work-related factors are all associated with work capacity impairment. |
3,666 | 63,708 | To examine the cellular mechanisms by which the proinflammatory cytokine interleukin-17 (IL-17) induces the synthesis of 92-kd gelatinase (matrix metalloproteinase 9 [MMP-9]) by human monocyte/ macrophages in primary culture.
IL-17-stimulated human monocytes isolated from the peripheral blood of healthy donors were cultured in the presence of antiinflammatory cytokines, neutralizing antibodies against IL-1beta, tumor necrosis factor alpha (TNFalpha), or IL-1 receptor antagonist, and with protein kinase inhibitors of diverse specificity. MMP measurements were performed using specific enzyme-linked immunosorbent assays, while the expression of specific messenger RNA was determined by Northern blotting. Detection of phosphorylated proteins and specific transcriptional factors was performed by Western blotting and by gel retardation experiments, respectively.
Biologically active IL-17 was detected in the synovial fluid of patients with rheumatoid arthritis. IL-17-induced MMP-9 production in human monocyte/ macrophages was dependent on endogenous prostaglandin E2 synthesis and related to autocrine stimulation by TNFalpha, but was IL-1beta independent. This activation involves both p42/44 and p38 kinases and nuclear factor kappaB. IL-17-inducible activator protein 1 and signal transducer and activator of transcription 1/3 may transactivate the MMP-9 promoter. | IL-17 may contribute to an unbalanced production of proinflammatory cytokines and MMP-9 in diseased articular joint tissues by interacting with the macrophages in the rheumatoid synovium. |
3,667 | 28,549 | To examine the association of socioeconomic status (SES) and delays in disease-modifying antirheumatic drug (DMARD) treatment with clinical measures in rheumatoid arthritis (RA) patients.
RA patients were recruited from rheumatology practices. We assessed SES based on education, occupation, and income, and divided patients into tertiles. The time from RA symptom onset to DMARD initiation (DMARD lag) was determined by self-report of the 2 dates, and distance to the rheumatologist (Distance) was obtained from Google Maps. We examined disease activity, determined by the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR); joint damage, determined from hand radiographs by Sharp scores; and physical disability, determined by the modified Health Assessment Questionnaire (M-HAQ). We used linear regression models to examine the relationship between clinical measures and SES, Distance, and DMARD lag.
We recruited 1,209 RA patients, 1,159 of whom had received DMARD treatment. Mean ± SD DMARD lag was 6.9 ± 9.0 years. On average, patients with lower SES waited 8.5 ± 10.2 years after onset of RA symptoms to begin DMARD treatment, compared to those in the middle and upper SES tertiles who waited 6.1 ± 7.9 years (P = 0.002) and 6.1 ± 8.6 years (P = 0.009), respectively. Each year of delayed treatment was associated with a DAS28-ESR increase of 0.02 (P ≤ 0.001), a Sharp score increase of 1.33 (P ≤ 0.001), and an M-HAQ score increase of 0.01 (P ≤ 0.001). | Low SES was associated with delay in DMARD initiation, and both were independently associated with worse clinical measures in RA. Strategies to reduce treatment delay in low-SES RA patients are needed. |
3,668 | 42,632 | The present study examines the possibility that a chronic pain condition, such as fibromyalgia, was associated with deficits in decision making and associative learning.
Fifteen patients with fibromyalgia (aged 42-59 years) and 15 healthy controls (aged 39-61 years) participated in the experiment. Subjects completed anxiety (STAI) and depression (BDI) questionnaires, as well as standardized neuropsychological tests (Stroop and WAIS subscales). In addition, an emotional decision-making task (Iowa Gambling Task) and a conditional associative learning task (CALT) were administered to all participants.
Results indicated that fibromyalgia had a poorer performance than healthy controls in both tasks, showing more perseveration errors in the learning task, and more disadvantageous decisions, as well as a more random behavior in the gambling task. Moreover, we observed that poor performance on the associative learning task was mediated by depression, whereas performance on the gambling task was not influenced by depression. No group differences were found on the standardized neuropsychological tests. | These findings indicate that pain and depressive symptoms in fibromyalgia might lead to significant deficits in emotionally charged cognitive tasks. Furthermore, it suggests that chronic pain might impose a high cost on executive control, undermining mainly affective processes involved in learning, memory, attention, and decision-making. |
3,669 | 33,781 | Doppler echocardiography has been demonstrated to be accurate in diagnosing valvular lesions in rheumatic heart disease (RHD) when compared to clinical evaluation alone.
To perform Doppler echocardiography in children clinically diagnosed by the Jones criteria to have acute rheumatic fever (ARF), and to then compare the effectiveness of echo in detecting single/multi-valvular lesions with that of the initial clinical evaluation.
We enrolled 93 children who were previously diagnosed with ARF by clinical examination. Presence of valvular lesions were enlisted, first by clinical auscultation, and then by performing Doppler echocardiography. We found that Doppler echocardiography was a sensitive technique, capable of detecting valvular lesions that were missed by clinical auscultation alone. Echocardiography of patients with carditis revealed mitral regurgitation to be the most common lesion present (53 patients, 56.98%), followed by aortic regurgitation in 21 patients (22.6%). The difference between clinical and echocardiographic diagnosis in ARF children with carditis was statistically significant for mitral regurgitation, aortic regurgitation and tricuspid regurgitation. Clinical auscultation alone revealed 4 cases of mitral stenosis, 39 mitral regurgitation, 14 aortic regurgitation, 9 tricuspid regurgitation; in contrast, echo revealed 5 cases of mitral stenosis, 53 mitral regurgitation, 21 aortic regurgitation, 18 tricuspid regurgitation. | Doppler echocardiography is a more sensitive technique for detecting valvular lesions. In the setting of ARF, echo enables a 46.9% higher detection level of carditis, as compared to the clinical examination alone. Echo was very significant in detecting regurgitation lesions, especially for cases of tricuspid regurgitation in the setting of multivalvular involvement. The results of our study are in accordance with previous clinical studies, all of which clearly demonstrate the advantages of Doppler echocardiography, paving the way for its probable inclusion as one of the Jones major criteria for diagnosing ARF. |
3,670 | 10,497 | The rheumatoid nodule is the most common extra-articular manifestation of rheumatoid arthritis. When present, it is readily identified in conventional hematoxylin and eosin sections.
We report a case with several rheumatoid nodules in a thyroid gland of a 33-year-old Greek woman with a 3-year history of rheumatoid arthritis treated with methotrexate, after having total thyroidectomy for hypothyroidism. | To the best of our knowledge, this is the first time that rheumatoid nodules have been encountered in the thyroid gland. |
3,671 | 54,542 | Chondrocytes in articular cartilage are surrounded by a narrow pericellular matrix (PCM), which together with the enclosed cell(s) are termed the "chondron". Although the precise function of this tissue region is unknown, previous studies provide indirect evidence that the PCM plays an important role in governing the local mechanical environment of chondrocytes. In particular, theoretical models of the chondron under mechanical loading suggest that the shape, size, and biomechanical properties of the PCM significantly influence the stress-strain and fluid flow environment of the cell. The goal of this study was to quantify the three-dimensional morphology of chondron in situ using en bloc immunolabeling of type VI collagen coupled with fluorescence confocal microscopy.
Three-dimensional reconstructions of intact, fluorescently labeled chondrons were made from stacks of confocal images recorded in situ from the superficial, middle, and deep zones of porcine articular cartilage of the medial femoral condyle.
Significant variations in the shape, size, and orientation of chondrocytes and chondrons were observed with depth from the tissue surface, revealing flattened discoidal chondrons in the superficial zone, rounded chondrons in the middle zone, and elongated, multicellular chondrons in the deep zone. | The shape and orientation of the chondron appear to reflect the local collagen architecture of the interterritorial matrix, which varies significantly with depth. Quantitative measurements of morphology of the chondron and its variation with site, disease, or aging may provide new insights into the influence of this structure on physiology and the pathology of articular cartilage. |
3,672 | 45,721 | Modern cementing techniques have improved glenoid fixation, reduced glenoid lucency seen with keeled components, and may eliminate differences attributable to glenoid design. The purpose of this study was to determine the effect of glenoid design on immediate and follow-up radiographic lucency of pegged and keeled glenoid components, using modern cementing techniques.
Fifty-three total shoulder arthroplasties were performed in patients with primary glenohumeral osteoarthritis. Patients were randomized prospectively to receive either a pegged or keeled glenoid component. Three raters graded radiographic glenoid lucencies.
On immediate radiographs, there was no significant difference in the rate of glenoid lucency between pegged (0%) and keeled (15%) glenoid components (P = .128). However, after an average of 26 months, the rate of glenoid lucency was significantly higher in patients with keeled components (46%) compared to patients with pegged components (15%) (P = .003). | Even with modern cementing techniques, pegged glenoid components remain radiographically superior to keeled glenoid components. |
3,673 | 5,725 | Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is characterized by variable clinical outcomes, activation of innate immune pattern-recognition receptors (PRRs), and accumulation of α-smooth muscle actin (α-SMA)-expressing myofibroblasts. The aim of this study was to identify an association between these entities and mitochondrial DNA (mtDNA), an endogenous ligand for the intracellular DNA-sensing PRRs Toll-like receptor 9 (TLR-9) and cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING), which has yet to be determined.
Human lung fibroblasts (HLFs) from normal donors and SSc-ILD explants were treated with synthetic CpG DNA and assayed for α-SMA expression and extracellular mtDNA using quantitative polymerase chain reaction for the human MT-ATP6 gene. Plasma MT-ATP6 concentrations were evaluated in 2 independent SSc-ILD cohorts and demographically matched controls. The ability of SSc-ILD and control plasma to induce TLR-9 and cGAS/STING activation was evaluated with commercially available HEK 293 reporter cells. Plasma concentrations of type I interferons (IFNs), interleukin-6 (IL-6), and oxidized DNA were measured using electrochemiluminescence and enzyme-linked immunosorbent assay-based methods. Extracellular vesicles (EVs) precipitated from plasma were evaluated for MT-ATP6 concentrations and proteomics via liquid chromatography mass spectrometry.
Normal HLFs and SSc-ILD fibroblasts developed increased α-SMA expression and MT-ATP6 release following CpG stimulation. Plasma mtDNA concentrations were increased in the 2 SSc-ILD cohorts, reflective of ventilatory decline, and were positively associated with both TLR-9 and cGAS/STING activation as well as type I IFN and IL-6 expression. Plasma mtDNA was not oxidized and was conveyed by EVs displaying a proteomics profile consistent with a multicellular origin. | These findings demonstrate a previously unrecognized connection between EV-encapsulated mtDNA, clinical outcomes, and intracellular DNA-sensing PRR activation in SSc-ILD. Further study of these interactions could catalyze novel mechanistic and therapeutic insights into SSc-ILD and related disorders. |
3,674 | 32,226 | Although chemokine stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 induce degradation of articular cartilage in rheumatoid arthritis (RA) and osteoarthritis (OA), the association between the SDF-1/CXCR4 pathway and degradation of the cartilaginous endplate and nucleus pulposus has not been thoroughly clarified. We investigated the expression of SDF-1 and CXCR4 in intervertebral discs (IVDs).
SDF-1 and CXCR4 levels in human IVDs and the rat L5/6 motion segment were quantified by enzyme-linked immunosorbent assay. SDF-1 staining was quantified using a microscope and Image-Pro Plus software. Integrated optical density (IOD) served as the measurement parameter. The number of CXCR4 immunoreactive cells was expressed as a percentage of the total number of cells.
SDF-1 and CXCR4 were both expressed in IVDs, and the levels of SDF-1 and CXCR4 were both significantly higher in the degeneration group than in the normal group of human (or rat) discs. Both nucleus pulposus cells and cartilaginous endplate cells expressed the CXCR4 protein. Furthermore, a positive correlation was observed between the SDF-1 IOD value and the percentage of CXCR4-positive disc cells in the nucleus pulposus and cartilaginous endplate. The SDF-1 IOD values were significantly higher in the outer annular fibrosus and bone/endplate junction region than in the nucleus pulposus and cartilaginous endplate in the rat specimens. | Our findings suggest upregulated expression of SDF-1 and its receptor CXCR4 in degenerated IVD. |
3,675 | 62,287 | Excess tissue matrix accumulates in systemic sclerosis (SSc), accounting for both visceral and dermal fibrosis. It is suggested that decreased serum levels of matrix metalloproteinases (MMPs) or increased levels of tissue inhibitors of matrix metalloproteinases (TIMPs) may account for this matrix accumulation.
To measure serum levels of tissue inhibitors of metalloproteinases, TIMP-1, TIMP-2, and collagenase-1 (MMP-1), in patients with diffuse cutaneous systemic sclerosis (dcSSc), limited cutaneous systemic sclerosis (lcSSc), primary Raynaud's phenomenon (RP), and in normal controls.
Serum samples from patients with dcSSc (n=83), lcSSc (n=87), RP (n=80), and normal controls (n=98) were analysed using enzyme linked immunosorbent assays (ELISAs) for total TIMP-1, TIMP-2, and MMP-1. Results from each assay were analysed by the Kruskal-Wallis test. Dunn's multiple comparison post-test was then applied between groups.
TIMP-1 levels were significantly raised in dcSSc and lcSSc groups compared with the RP group and normal controls (p<0.01 to p<0.001). In the dcSSc group, TIMP-1 levels were significantly higher in early disease (<2 years) than in late stage disease (>4 years) (p<0.05). This was not found for the lcSSc group. Serum TIMP-2 and MMP-1 levels in dcSSc and lcSSc did not differ significantly from those in normal controls. Increased levels of TIMPs were not convincingly associated with organ disease. No assay result correlated with autoantibody status (anti-topoisomerase 1 (anti-Scl-70), anticentromere antibody, or anti-RNA polymerase). No significant differences in serum TIMP-1, TIMP-2, or MMP-1 levels were shown in the RP group compared with normal controls. | Raised TIMP-1 levels in the SSc groups support the hypothesis that matrix accumulation occurs in SSc at least in part owing to decreased degradation. Moreover, the variation in TIMP-1 levels between the early and late disease stages of dcSSc seems to reflect the early progressive course of dermal fibrosis seen clinically. The expected reduction in serum MMP-1 levels in the SSc groups was not found. This suggests that tissue matrix accumulation is due to increased inhibitors rather than to decreased MMPs. |
3,676 | 51,717 | Optimal matrix metabolism by articular chondrocytes is controlled by the 'set-point' volume which is determined mainly by membrane transporters. The signal transduction pathway(s) for the key membrane transporter which responds to cell swelling ('osmolyte channel') and mediates regulatory volume decrease (RVD) is poorly understood, so here the role of Ca2+ and the effects of 2D culture have been clarified.
Changes to the volume and intracellular calcium levels ([Ca2+]i) of freshly isolated and 2D cultured bovine articular chondrocytes subjected to hypotonic challenge using a 43% reduction in medium osmolarity were studied by single-cell fluorescence microscopy. The effects of ethylene glycol tetraacetic acid (EGTA), REV5901 and Gd(3+) were studied and the role of Ca2+ influx determined by Mn2+ quench.
In freshly isolated cells, approximately 50% of chondrocytes exhibited 'robust RVD' (6[120]). RVD was inhibited by REV 5901 (4+/-2% responding) (3[23]) and 2 mM EGTA (18+/-5% responding) (4[166]) whereas Gd3+ had no effect (3[89]). The hypotonic challenge resulted in a Gd3+-insensitive rise in [Ca2+]i that did not correlate with RVD in all cells. Following 2D culture, chondrocytes also demonstrated Gd3+-insensitive RVD, but in contrast, the [Ca2+]i rise was blocked by this agent. | The data suggested that in freshly isolated and 2D cultured chondrocytes, the rise in [Ca2+]i occurring during hypotonic challenge could be related to RVD, but only in some cells. However, with 2D culture, the Ca2+ response switched to being Gd3+-sensitive, suggesting that as a result of changes to chondrocyte shape, stretch-activated cation channels although present, do not appear to play a role in volume regulation. |
3,677 | 38,318 | To define for the first time the transcriptomes of normal and end-stage osteoarthritis (OA) hip cartilage.
RNA was isolated from cartilage within 2h of joint replacement surgery. Gene expression was analyzed using Agilent GeneSpring GX 11 following hybridization to Illumina Human HT-12 V3 microarrays. Real-time reverse-transcription polymerase chain reaction (RT-PCR) was used to validate the expression of six genes identified by microarray as differentially expressed. Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) were used to investigate enriched functions or canonical pathways amongst differentially expressed genes respectively.
In total we identified 998 differentially expressed genes (fold change ≥ ±1.5, P-value ≤ 0.01) between neck of femur fracture (NOF) (n = 10) and OA hip (n = 9) patient cartilage. These differentially expressed genes were enriched within 71 canonical pathways. A comparison between a comparable knee dataset(20) only identified 229 genes similarly differentially expressed although remarkably 34 canonical pathways overlapped between experiments. | This study is the first to report a comprehensive gene expression analysis of human hip OA cartilage compared to control (NOF) cartilage at the whole-genome level. Our differential gene expression dataset shows excellent correlation with similar defined studies using comparable tissue but reveals discord between hip and knee OA at the individual gene status but with commonality with regards the molecular pathways involved. |
3,678 | 14,970 | Recent studies demonstrate autoantibodies are powerful tools to interrogate molecular events linking cancer and the development of autoimmunity in scleroderma. Investigating cancer risk in these biologically relevant subsets may provide an opportunity to develop personalised cancer screening guidelines. In this study, we examined cancer risk in distinct serologic and phenotypic scleroderma subsets and compared estimates with the general population.
Patients in the Johns Hopkins Scleroderma Center observational cohort were studied. Overall and site-specific cancer incidence was calculated in distinct autoantibody and scleroderma phenotypic subsets, and compared with the Surveillance, Epidemiology and End Results registry, a representative sample of the US population.
2383 patients with scleroderma contributing 37 686 person-years were studied. 205 patients (8.6%) had a diagnosis of cancer. Within 3 years of scleroderma onset, cancer risk was increased in patients with RNA polymerase III autoantibodies (antipol; standardised incidence ratio (SIR) 2.84, 95% CI 1.89 to 4.10) and those lacking centromere, topoisomerase-1 and pol antibodies (SIR 1.83, 95% CI 1.10 to 2.86). Among antipol-positive patients, cancer-specific risk may vary by scleroderma subtype; those with diffuse scleroderma had an increased breast cancer risk, whereas those with limited scleroderma had high lung cancer risk. In contrast, patients with anticentromere antibodies had a lower risk of cancer during follow-up (SIR 0.59, 95% CI 0.44 to 0.76). | Autoantibody specificity and disease subtype are biologically meaningful filters that may inform cancer risk stratification in patients with scleroderma. Future research testing the value of targeted cancer screening strategies in patients with scleroderma is needed. |
3,679 | 53,580 | To evaluate the development of cataract and the results of cataract surgery with intraocular lens (IOL) implantation in patients with chronic uveitis associated with juvenile idiopathic arthritis (JIA).
A hospital-based retrospective case series consisted of 25 patients with JIA-associated uveitis. The mean age of the patients was 5.8 years at the onset of arthritis and 6.8 years at the onset of uveitis. During the 15-year study period cataract surgery with implantation of an IOL was performed in 36 eyes. In 17 eyes phacoemulsification and initial posterior capsulectomy with anterior core vitrectomy were performed. The treatment of JIA and uveitis was carefully adjusted with systemic immunosuppressive drugs and topical corticosteroids perioperatively. The mean postoperative follow-up period was 3.3 years.
The first signs of cataract were observed 2.3 years (mean) after the diagnosis of uveitis and the cataract operation of the first eye was performed 4.5 years (mean) after the diagnosis of uveitis. After IOL surgery the visual result was good (> or = 0.5) in 64%, moderate (0.3 to < 0.5) in 11% and impaired (< 0.3) in 25% of eyes. Secondary cataract developed in 16 eyes but in none of the eyes with initial posterior capsulectomy and core vitrectomy. Secondary glaucoma developed in 18 eyes, retinal detachment in 2, cystoid macular edema in 16 and band keratopathy in 12 eyes. | Cataract is an early complication of JIA-associated uveitis. Under strict control of uveitis, IOL implantation is an important alternative in visual rehabilitation for this type of patient. |
3,680 | 45,984 | To identify gaps in therapy with urate-lowering drugs for the treatment of gout as well as factors associated with resuming therapy.
From 2 integrated delivery systems, we identified patients 18 years or older with a diagnosis of gout who initiated use of a urate-lowering drug from January 1, 2000 through June 30, 2006 and who had a gap in therapy. A gap was defined as a period of over 60 days after the completion of 1 prescription in which no refill for a urate-lowering drug was obtained. Survival curves were used to assess return to therapy of urate-lowering drugs. Cox proportional hazards analysis estimated the association between covariates and return to therapy.
There were 4166 new users of urate-lowering drugs (97% received allopurinol), of whom 2929 (70%) had a gap in therapy. Among those with a gap, in 75% it occurred in the first year of therapy. Fifty percent of patients with a gap returned to therapy within 8 months, and by 4 years it was 75%. Age 45-74 years (<45 referent) and greater duration of urate-lowering drug use before the gap was associated with resuming treatment within 1 year. In contrast, receipt of nonsteroidal anti-inflammatory drugs or glucocorticoids in the year before the gap was associated with a reduced likelihood of resuming therapy. | The majority of gout patients with gaps in urate-lowering drug use returned to treatment. More investigation is needed to better understand why patients may go for months without refilling prescriptions, given the clinical consequences of nonadherence. |
3,681 | 21,364 | Fibromyalgia (FM) and hyperparathyroidism may present similar symptoms (musculoskeletal pain, cognitive disorders, insomnia, depression and anxiety), causing diagnostic confusion.
To determine the frequency of asymptomatic hyperparathyroidism in a sample of patients with FM and to evaluate the association of laboratory abnormalities to clinical symptoms.
Cross-sectional study with 100 women with FM and 57 healthy women (comparison group). Parathyroid hormone (PTH), calcium and albumin levels were accessed, as well as symptoms in the FM group.
In FM group, mean serum calcium (9.6±0.98mg/dL) and PTH (57.06±68.98pg/mL) values were considered normal, although PTH levels had been significantly higher than in the comparison group (37.12±19.02pg/mL; p=0.001). Hypercalcemic hyperparathyroidism was diagnosed in 6% of patients with FM, and 17% of these women exhibited only high levels of PTH, featuring a normocalcemic hyperparathyroidism, with higher frequencies than those expected for their age. There was no significant association between hyperparathyroidism and FM symptoms, except for epigastric pain, which was more frequent in the group of patients concomitantly with both diseases (p=0.012). | A high frequency of hyperparathyroidism was noted in women with FM versus the general population. Normocalcemic hyperparathyroidism was also more frequent in patients with FM. Longitudinal studies with greater number of patients are needed to assess whether this is an association by chance only, if the increased serum levels of PTH are part of FM pathophysiology, or even if these would not be cases of FM, but of hyperparathyroidism. |
3,682 | 20,479 | To report on the 5-year efficacy and safety results of the AMBITION (Actemra versus Methotrexate double-Blind Investigative Trial In mONotherapy) monotherapy study (ClinicalTrials.gov: NCT00109408, NCT00720798).
Patients with rheumatoid arthritis for whom biologics had not failed or who did not discontinue methotrexate because of lack of efficacy or tolerability were followed up for 5 years to assess the efficacy and serious adverse events (SAE) of tocilizumab (TCZ) monotherapy.
Longterm efficacy results showed that efficacy was maintained or improved for up to 264 weeks in patients receiving TCZ monotherapy. Serious infection was the most frequent SAE; no new safety signals were reported. | Longterm monotherapy with TCZ demonstrated continuing efficacy and safety. |
3,683 | 64,470 | Samarium-153 particulate hydroxyapatite (Sm-153 PHYP) is a relatively new radiation synovectomy agent developed for the treatment of chronic synovitis. Although it has been shown that the levels of unwanted extra-articular radiation are lower after intra-articular injection of Sm-153 PHYP than yttrium-90 colloid, its clinical efficacy has not been rigorously studied.
To establish whether Sm-153 PHYP radiation synovectomy results in a clinically useful benefit sustained at one year.
In a randomised double blind study, patients received either intra-articular 40 mg triamcinolone hexacetonide alone or 40 mg triamcinolone hexacetonide combined with Sm-153 PHYP in an outpatient clinic.
Sixty patients (28 male, 32 female), median age 51 (18-75) with chronic knee synovitis were studied. Diagnoses included: rheumatoid arthritis (n=29); psoriatic arthritis (n=9); ankylosing spondylitis (n=3); reactive arthritis (n=2); undifferentiated seronegative oligoarthritis (n=13) and miscellaneous inflammatory conditions (n=4). More patients who received Sm-153 PHYP/triamcinolone hexacetonide sustained clinical benefit a year after treatment compared with patients who received corticosteroid alone (12 of 31 (39%) v 6 of 29 (21%), a difference of 18% more patients (95% CI -5% to 41%)) though the difference was not significant (chi(2)=2.31, 0.2>p>0.1, n=60). Despite the variation in injected activity (median 563 MBq, range 218-840 MBq), there was no obvious relation between low levels of injected activity (<555 MBq) and relapse within 12 months of treatment (chi(2) =2.61, 0.2>p>0.1, n=31). | There was no clear beneficial clinical effect of combined Sm-153 PHYP/triamcinolone hexacetonide injection over triamcinolone hexacetonide alone a year after treatment for chronic knee synovitis. |
3,684 | 48,705 | Although transforming growth factor beta1 (TGFbeta1) is known to be a potent inhibitor of proliferation in most cell types, it accelerates proliferation in certain mesenchymal cells, such as articular chondrocytes and nucleus pulposus cells. The low ability for self-renewal of nucleus pulposus cells is one obstacle in developing new therapeutic options for intervertebral disc diseases, and utilizing cytokines is one of the strategies to regulate nucleus pulposus cell proliferation. However, the precise cell cycle progression and molecular mechanisms by which TGFbeta1 stimulates cell growth remain unclear. The aim of this study was to elucidate a mechanism that enables cell proliferation with TGFbeta1 stimulation.
We tested cultured rat nucleus pulposus cells for proliferation and cell cycle distribution under exogenous TGFbeta1 stimulation with and without putative pharmaceutical inhibitors. To understand the molecular mechanism, we evaluated the expression levels of key regulatory G1 phase proteins, c-Myc and the cyclin-dependent kinase inhibitors.
We found that TGFbeta1 promoted proliferation and cell cycle progression while reducing expression of the cyclin-dependent kinase inhibitors p21 and p27, which are downregulators of the cell cycle. Robust c-Myc expression for 2 h and immediate phosphorylation of extra cellular signal regulated kinase (ERK1/2) were detected in cultures when TGFbeta1 was added. However, pretreatment with 10058-F4 (an inhibitor of c-Myc transcriptional activity) or PD98059 (an inhibitor of ERK1/2) suppressed c-Myc expression and ERK1/2 phosphorylation, and inhibited cell cycle promotion by TGFbeta1. | Our experimental results indicate that TGFbeta1 promotes cell proliferation and cell cycle progression in rat nucleus pulposus cells and that c-Myc and phosphorylated ERK1/2 play important roles in this mechanism. While the difference between rat and human disc tissues requires future studies using different species, investigation of distinct response in the rat model provides fundamental information to elucidate a specific regulatory pathway of TGFbeta1. |
3,685 | 30,524 | To study the synergistic effects of electroacupuncture on the treatment of knee osteoarthritis after arthroscopic debridement.
From May 2008 to July 2010, 78 patients with knee osteoarthritis were randomly divided into two groups. There were 42 patients in the experimental group, including 16 males and 26 females, ranging in age from 41 to 63 years, with an average of (53.62 +/- 6.53) years; the disease course ranged from 8 to 24 months, with an average of (10.35 +/- 6.42) months. The patients were treated with arthroscopic debridement combined with electroacupuncture after operation. There were 36 patients in the control group, including 14 males and 22 females, ranging in age from 40 to 62 years, with an average of (54.34 +/- 7.67) years; the disease course ranged from 6 to 25 months, with an average of (11.94 +/- 5.13) months. Those patients were treated only with arthroscopic debridment. All the patients performed isometric quadriceps femoris contraction exercise and knee flexion and extension activities after operation. The visual analog scale(VAS) score and Lysholm knee score were used to evaluate the therapeutic effects.
All the patients were followed up, and the duration ranged from 12 to 30 months, with an average of 15.6 months. At the final follow-up, VAS score was significantly decreased, and the Lysholm score, except for the item demanding for support, significantly increased, compared with those before surgery respectively in both groups. There was significant difference in VAS score between two groups after treatment. As to Lysholm score, there were significant differences in limp, pain, swelling, stair activity and squat, but there were no significant differences in items of interlocking and instability between two groups after treatment. | Electroacupuncture can effectively improve the clinical symptoms and knee joint's motor function of knee joints in patients with knee osteoarthritis, as well as the synergistic effects on the treatment of knee osteoarthritis after arthroscopic debridement, leading to a much better long-term therapeutic effect with respect of improving the function of knee joint. This therapy, combined with traditional Chinese medicine and Western Medicine,is worth of clinical application in the treatment of knee osteoarthritis. |
3,686 | 47,690 | To examine adherence to adalimumab (ADA) and etanercept (ETA) and health care costs in rheumatoid arthritis (RA) patients, and to explore the association between adherence, utilization and costs.
Using administrative claims data from a large managed health care plan, RA patients treated with etanercept or adalimumab during the period from 01/01/2005 through 12/31/2005 were identified. The first dispensing date was defined as the index date. Patient adherence and costs were assessed during the 1 year post-index period.
Nonadherence (medication possession ratio <80%) was modeled using logistic regression. Hazard ratios (HR) comparing time to discontinuation were estimated using Cox proportional hazard (PH) models. Propensity score matching with multivariate generalized linear modeling adjustment was done to assess cost difference between ADA and ETA.
Of 3829 eligible RA patients, 1292 (765 existing, 527 naïve) and 2537 (1834 existing, 703 naïve) patients used ADA and ETA, respectively. Compared with ADA users, ETA users had longer average treatment duration (316 vs. 291 days; p < 0.0001). Unadjusted adherence rates for naïve and existing users were 63% and 70% (ADA), and 65% and 73% (ETA). Logistic regression analysis indicated that compared with ETA users, ADA users were more likely to be nonadherent (OR, naïve 1.24; existing; 1.25). Cox PH models indicated that existing ADA users were more likely to discontinue (HR = 1.11; p = 0.06) their medication than existing ETA users. Compared with ADA users, ETA users had significantly lower RA-related pharmacy costs (naïve: $10,892 vs. $12,534, p < 0.01; existing: $12,192 vs. $13,752, p < 0.01) and RA-related total costs (naïve: $11,976.42 vs. $13,511.99, p < 0.05; existing: $14,031 vs. $15,454, p < 0.05). | ETA users had longer treatment duration, were more likely to adhere to their medication regimen and had lower RA-related pharmacy and RA-related total costs compared with ADA users. These findings must be considered within the limitations of this database analysis. |
3,687 | 16,692 | To evaluate the prevalence and type of rheumatic immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs), as well as the correlation with tumour response.
This was a single-centre prospective observational study including all cancer patients receiving ICIs. The occurrence of irAEs and tumour response was assessed on a regular basis. Patients who experienced musculoskeletal symptoms were referred to the department of rheumatology for clinical evaluation and management.
From September 2015 to May 2017, 524 patients received ICIs and 35 were referred to the department of rheumatology (6.6%). All but one of the rheumatic irAEs occurred with anti-programmed cell death protein 1(PD-1)/PD-1 ligand 1(PD-L1) antibodies, with a median exposure time of 70 days. There were two distinct clinical presentations: (1) inflammatory arthritis (3.8%) mimicking either rheumatoid arthritis (n=7), polymyalgia rheumatica (n=11) or psoriatic arthritis (n=2) and (2) non-inflammatory musculoskeletal conditions (2.8%; n=15). One patient with rheumatoid arthritis was anti-cyclic citrullinated peptide (anti-CCP) positive. Nineteen patients required glucocorticoids, and methotrexate was started in two patients. Non-inflammatory disorders were managed with non-steroidal anti-inflammatory drugs, analgesics and/or physiotherapy. ICI treatment was pursued in all but one patient. Patients with rheumatic irAEs had a higher tumour response rate compared with patients without irAEs (85.7% vs 35.3%; P<0.0001). | Since ICIs are used with increasing frequency, knowledge of rheumatic irAEs and their management is of major interest. All patients were responsive either to low-to-moderate doses of prednisone or symptomatic therapies and did not require ICI discontinuation. Furthermore, tumour response was significantly higher in patients who experienced rheumatic irAEs. |
3,688 | 35,115 | To evaluate radiographic progression in patients with ankylosing spondylitis (AS) receiving two different doses of the tumour necrosis factor antagonist golimumab.
356 patients with AS were randomly assigned to placebo, or golimumab 50 mg or 100 mg every 4 weeks (wks). At wk16, patients with inadequate response early escaped with blinded dose adjustments (placebo→golimumab 50 mg, 50 mg→100 mg). At wk24, patients still receiving placebo crossed over to golimumab 50 mg. Lateral view radiographs of the cervical/lumbar spine were obtained at wk0, wk104 and wk208, and scored (two blinded readers, modified Stoke AS Spine Score (mSASSS)). Observed data were used for wk104 analyses; missing wk208 scores were linearly extrapolated.
Wk104 changes from baseline in mSASSS averaged 1.6±4.6 for placebo crossover, 0.9±2.7 for 50 mg and 0.9±3.9 for 100 mg. By wk208, following golimumab therapy for 3.5-4 years, mean changes in mSASSS were 2.1±5.2 for placebo crossover, 1.3±4.1 for 50 mg and 2.0±5.6 for 100 mg. Less than a third of patients (placebo crossover, 19/66 (28.8%); 50 mg, 29/111 (26.1%); 100 mg, 35/122 (28.7%)) had a definitive change from baseline mSASSS (>2). Less radiographic progression was observed through wk208 in patients without baseline syndesmophytes (0.2 vs 2.8 in patients with ≥1 syndesmophyte; p<0.0001) and with baseline C-reactive protein (CRP) levels ≤1.5 mg/dl (0.9 vs 2.9 with CRP >1.5 mg/dl; p=0.0004). | No difference in mSASSS change was observed between golimumab 50 mg and 100 mg. The radiographic progression rate remained stable at years 2 and 4, suggesting no acceleration of new bone formation over time. Golimumab-treated AS patients with no syndesmophytes and less systemic inflammation at baseline had considerably less radiographic progression. |
3,689 | 33,273 | This prospective study assessed the 10-year clinical outcomes of periosteum autologous chondrocyte implantation (ACI) due to cartilage lesions of the femoral condyles.
Thirty-three of 45 patients (3 failures, 7 non-responders, 2 others) were available for clinical and radiographic evaluation at 2, 5, and 10 years. Patients were categorized into groups with focal cartilage lesions, osteochondritis dissecans (OCD), and cartilage lesions with simultaneous ACL reconstruction (ACL). Seven patients in the overall series required an arthroscopic re-intervention (3 ACI related, 4 ACI unrelated).
Subjective knee scores and activity scores were significantly improved at 2 years toward their pre-operative levels and then remained stable up to 10 years; however, patients did not reach their pre-injury activity levels. Upon 10-year examination, using the IKDC knee examination form, there were 15 normal, 11 nearly normal, 5 abnormal, and 2 severely abnormal knees. Radiographic evidence of osteoarthritis was found in 45% of patients (5 focal lesions, 2 OCD, and 8 ACL).
Case series, Level IV. | ACI provided safe and stable performance of operated knees over 10 years with a significant improvement toward pre-operative levels. Patients restrained from high-impact knee joint activities, post-surgery, and their knee radiographs demonstrated a high incidence of knee OA in trauma-related lesions. Optimal long-term performance is expected in localized, low-impact cartilage lesions of young patients. |
3,690 | 56,695 | To report clinical manifestations and demographic characteristics of patients with rheumatic fever treated in a public hospital in the state of Acre.
A cross-sectional study was conducted of patients consecutively seen in the Cardiology Ward at FUNDHACRE Demographic, clinical and laboratory data were assessed through a questionnaire. The diagnosis of rheumatic fever was made based on Jones' criteria, associated with laboratory data, electrocardiography, chest X-ray, and bi-dimensional echocardiography. Patients with other heart diseases, diabetes, obesity, inflammatory disease, and infections were excluded. Those who smoked, were pregnant, or used anti-inflammatory medication or hormone therapy were also excluded.
From July 2003 to February 2004, 99 patients with rheumatic fever were assessed (mean age, 11 years, SD= +/- 10.18) with a predominance of females (59.6%), and a racial phenotype of a mixture of Caucasian and Indian (60.6%). Three individuals were excluded because they did not meet the diagnostic criteria. Mean age was 9.1 years old, and in 30.4% of the patients, the disease was diagnosed at the first episode of rheumatic fever. The most frequent clinical manifestations were carditis (69.7%), arthritis (21.4%), and chorea (6.1%). Mitral regurgitation was the most common lesion (36.4%) followed by the association of mitral regurgitation and aortic regurgitation (9.1%). | Rheumatic carditis was the most common manifestation of rheumatic fever, predominant in the group with a racial mixture of Caucasian and Indian (60.6%). Low compliance with antibiotic therapy contributed to the recurrence of the disease and to cardiac sequelae. |
3,691 | 67,828 | To analyse major histocompatibility complex (MHC) haplotypes in Mexican mestizo patients with seronegative spondyloarthropathies (SSpA) and normal controls, to discover if there are other antigens, besides B27, in the HLA region that might show association with the disease.
The study included 100 Mexican mestizo patients with SSpA and 200 of their first degree relatives. These groups were compared with 85 ethnically matched controls. The class I and class III MHC antigens were obtained by standard methods. The significance of differences between patients and controls was tested by chi 2 analysis; linkage disequilibrium among the different alleles in each haplotype was estimated by computing delta values.
We found a significantly increased frequency of the HLA-B27 antigen (pcorr. = 1 x 10(-5), odds ratio (OR) = 33.4, 95% confidence interval (CI) = 9.3-142.0). In the group of 45 SSpA patients negative for the B27 antigen, independent increased frequencies of HLA-B49 antigen (pcorr. = 0.03, OR = 6.5, 95% CI = 1.5-32.8)) and the FC31 complotype (pcorr. = 0.04, OR = 3.7, 95% CI = 1.2-11.1) were found. Significant delta values were obtained for the [B27;SC30] haplotype (p = 0.0005) but not for haplotypes marked by the FC31 complotype. HLA-B antigens on the homologous chromosome in B27 positive patients were mainly HLA-B51 (18%) and HLA-B60 (16%); however, the observed genotypes B27/B51 and B27/B60 were not significantly different than expected from the allele frequencies alone. | These data suggest that in Mexicans additional genes within the MHC region besides the HLA-B27 antigen, might be related to the genetic susceptibility for developing SSpA. Relevant antigens included the HLA-B49 and the FC31 complotype. |
3,692 | 29,046 | This study has the objective to systematize scientific evidences about the use of muscle stretching exercises in the treatment of FM.
It was performed from retrospective research without chronological and linguistic limits, at databases of MEDLINE, LILACS, SciELO and PEDro, as well as at PubMed search tool. Data collection was performed by two independent reviewers in October 2012, with the search strategy formulated by crossing descriptors and relevant terms to the topic in English, Portuguese and Spanish languages. Randomized clinical trials, only with patients with a clinical diagnosis of fibromyalgia and muscle stretching exercises as a therapeutic measure at least in one of the intervention groups were included. Included studies were assessed for methodological quality using PEDro scale and their references analyzed to highlight additional sources. The search amounted to an average of 6,794 items. Only five articles were selected, one being excluded because of its low methodological quality. Pain was assessed unanimously. The method and timing of interventions varied widely, there was poor mention of the parameters used in the stretches and absence of specific physical examinations.
There was significant improvement in all studies regarding pain, besides as related to quality of life and physical condition. | It is clear the importance of muscle stretching in the treatment of FM, however, there is a need for further studies to establish the real benefits of the technique, because the majority of published studies shows low methodological quality and there is a lack of standardization regarding the use of this resource. |
3,693 | 16,478 | We tested whether GW0742, a peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) agonist, improves endothelial dysfunction induced by plasma from patients with systemic lupus erythematosus (SLE) involving the inhibition of endoplasmic reticulum (ER) stress.
A total of 12 non-pregnant women with lupus and 5 non-pregnant healthy women (controls) participated in the study. Cytokines and double-stranded DNA autoantibodies (anti-dsDNA) were tested in plasma samples. Endothelial cells, isolated from human umbilical cord veins (HUVECs), were used to measure nitric oxide (NO), intracellular reactive oxygen species (ROS) production, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and ER stress markers.
Interferon-γ, interleukin-6, and interleukin-12 levels were significantly increased in plasma from patients with SLE with active nephritis (AN), as compared to both patients with SLE with inactive nephritis (IN) and the control group. The NO production stimulated by both the calcium ionophore A23187 and insulin was significantly reduced in HUVECs incubated with plasma from patients with AN-SLE as compared with the control group. Plasma from patients with IN-SLE did not modify A23187-stimulated NO production. Increased ROS production and NADPH oxidase activity were found in HUVECs incubated with plasma from patients with AN-SLE, which were suppressed by the ER stress inhibitor 4-PBA and the NADPH oxidase inhibitors, apocynin and VAS2870. GW0742 incubation restored the impaired NO production, the increased ROS levels, and the increased ER stress markers induced by plasma from patients with AN-SLE. These protective effects were abolished by the PPARβ/δ antagonist GSK0660 and by silencing PPARβ/δ. | PPARβ/δ activation may be an important target to control endothelial dysfunction in patients with SLE. |
3,694 | 33,595 | The aim of our study was to compare dual-energy CT (DECT) with US for the diagnosis of gouty arthritis and to correlate the imaging findings with results from synovial fluid aspiration whenever possible.
We recruited 21 patients (17 male and 4 female) who presented with a clinical suspicion of acute or chronic gout in 37 joints. DECT scans of the hands, wrists, feet, ankles, knees and elbows were performed. For post-processing, a colour-coding gout software protocol was used. US examinations of the same joints were performed. In addition, joint fluid aspiration was performed in a total of 14 joints.
DECT images were positive for urate crystal deposits in 25 of 37 joints. US findings were positive in 24 of 37 examined joints. In 12 of 14 joints the synovial fluid aspiration was positive. CT and US findings correlated in 32 of 37 joints (86.5%; κ = 0.698, P < 0.001). CT and synovial fluid results correlated in 12 of 14 joints (85.7%; κ = 0.417, P = 0.119). US and cytology findings correlated in 14 of 14 joints (100%; κ = 1, P < 0.001). | DECT and US have comparable sensitivity for the detection of gouty arthritis in a clinical setting. However, DECT results should be interpreted carefully, as there could be some false-negative findings. |
3,695 | 54,887 | Adult-onset Still's disease (AOSD) is considered a rare disease, but few data exist on the incidence and prevalence of AOSD. This study has analysed the epidemiology, disease presentation, and outcome of AOSD in a stable homogeneous population in Northern Norway.
A retrospective cohort study of all AOSD patients registered in 1990-2000 at the only hospital in the region with a Rheumatology Service. Clinical diagnosis and exclusion of patients were directed by the Yamaguchi criteria for AOSD. Demographic and clinical data at baseline were extracted from patient records and supplemented with data gathered at control visits. Data were analysed with nonparametric methods.
AOSD was ascertained in 13 patients; the estimated annual AOSD incidence was 0.4/100,000 adults (95% CI 0.11-0.97), while point prevalence of AOSD increased from 3.4/100,000 (95% CI 0.8-9.4) in 1990 to 6.9/100,000 in 2000 (95% CI 2.7-14.2). Mean diagnostic delay was 5.2 months (range 0.5-18). Serum ferritin > 5 times the normal upper level had 63% diagnostic sensitivity. During 69 months' follow-up, one patient died, 6/13 patients achieved sustained remission, while six patients developed a chronic progressive (n = 3) or a relapsing/remitting disease course (n = 3). Four of these six patents had to enter social security programmes. | The annual incidence of AOSD in Northern Norway is at least 0.4/100,000 adults. AOSD in this region is more prevalent than in France or Japan, affects more males, and approximates to the prevalence of juvenile Still's disease. Half of all patients have a monocyclic disease course, while mortality and invalidity occur in patients with chronic disease. |
3,696 | 20,553 | Patients who undergo either primary or revision total hip arthroplasty (THA) mainly expect improvement in pain, function/activity and quality of life. The purpose of the study was to measure the degree of short-term and medium-term improvement and the differences in patient-reported outcome that can be expected in patients undergoing revision THA, compared to patients undergoing primary THA.
In this study, the results of patient-reported outcome measurements were compared in 124 matched patients, who underwent revision surgery and primary THA between 01/2007 and 12/2009. Assessment was performed at short-term and medium-term follow-up and included the WOMAC score, the UCLA activity score and EuroQol scores.
6 months after revision THA, the mean total WOMAC score improved by 22.1 points, the UCLA activity score by 0.6 points and the EuroQol-Index by 0.2 points. After primary THA, the improvement was 41.4 points on the WOMAC, 1.1 points on the UCLA and 0.3 points on the EuroQol-Index. At medium-term follow-up, 3.6 years after revision surgery and 2.3 years after primary THA, patients undergoing revision THA showed significantly less overall improvement, as well as lower final outcome scores, than patients undergoing primary THA. | Patients undergoing revision arthroplasty, as well as patients undergoing primary THA, can expect major improvement in function, activity and quality of life postoperatively. However, overall level of improvement, as well as peak attainable outcome levels, are lower after revision surgery than after primary THA. Appropriate information for patients who undergo hip revision surgery is necessary in order to avoid unrealistic expectations and postoperative dissatisfaction. |
3,697 | 55,069 | Musculoskeletal conditions are a major burden on individuals, health systems, and social care systems. The objective of the MAPPING study was to assess the impact of musculoskeletal conditions on health-related quality of life (HRQL) in an Italian population sample.
Trained rheumatologists carried out structured visits in which subjects were asked about musculoskeletal symptoms and socio-demographic characteristics, completed validated instruments for measuring HRQL, such as the Short Form 36 items status survey questionnaire (SF-36), the EUROQoL five item questionnaire (EQ-5D), and chronic pain severity (Chronic Pain Grade - CPG questionnaire), and underwent a standardized physical examination. We considered a sample size of 576 patients diagnosed as having had musculoskeletal conditions. For the purposes of this study, musculoskeletal diseases were classified into 4 diagnostic groups: inflammatory rheumatic diseases (IRD), symptomatic peripheral osteoarthritis (SPOA), low back pain (LBP), and soft tissue disorders (STD). Cases were defined by previously validated criteria.
The 4 major musculoskeletal disease groups, compared to non-sufferers, significantly impaired all eight health concepts of the SF-36 in the following order of magnitude: IRD, SPOA, STD, and LBP. Similar results were found for EQ-5D. The most striking impact was seen for SF-36 physical measures. On multiple regression modelling the physical component (PCS) of the SF-36 was influenced by female sex, age, high BMI, and low educational level (all at a p level < 0.001), and by manual occupation (p = 0.028) and chronic co-morbidity (p = 0.035) in LBP In SPOA, factors influencing physical function were age (p = 0.0001), low educational level (p = 0.006), female sex (p = 0.028), and chronic co-morbidity (p = 0.037). Moreover, an association on chronic co-morbidity and low educational level (both at a p level < 0.001), age (p = 0.004), and manual occupation (p = 0.035) was found with IRD, as well as of chronic co-morbidity and low educational level (both at a p level < 0.001), female sex (p = 0.006) and high BMI (p = 0.036) with STD were also found. Similar results were found for EQ-5D. | The MAPPING study indicates that musculoskeletal conditions have a clearly detrimental effect on the HRQL and one third of the adult population in Italy visited at least one physician for musculoskeletal problem in the past year. These results enable a comparison to be made of the burden of musculoskeletal conditions with that of other common chronic conditions. |
3,698 | 5,590 | To report radiologic, functional outcomes, and complications with a long-term follow-up in acute olecranon fractures treated with osteosynthesis and, secondly, to determine the predisposing factors to arthritis.
Forty-two patients treated with osteosynthesis for acute olecranon fractures were reviewed, with a minimum follow-up of 24 months. Radiological and clinical evaluations including DASH, MEPS, active range of motion, pain, arthritis, associated lesions, and complications were recorded. Arthritis was classified according to Broberg-Morrey scale. A logistic regression model was estimated to determine risk factors to develop ulnohumeral arthritis. The association between the types of fractures according to Mayo classification and MEPS, and the association between the type of fracture and the presence of pain were analyzed.
The average follow-up was of 43.64 months. The flexion-extension average range was 135.6°, and the mean MEPS was 89.45; the DASH was 25.26. Eighteen cases (42.86%) were fixed with pre-contoured locking plates, 21 with tension band wiring (50%), and 3 with cannulated screws of 7 mm (7.14%). Six cases (14.29%) needed hardware removal. All fractures healed. Ulnohumeral osteoarthritis was observed in 14 cases (33.3%). We did not find a significant association among the MEPS, pain, and the fracture type, according to Mayo (p > 0.1 for both values). A significant association was found (p < 0.05) between fracture type and the osteoarthritis. | In olecranon fractures, good functional and radiological results with low complications are predictable. The osteoarthritis is possible in more complex fractures and with other associated fractures. |
3,699 | 10,468 | It is accepted that the optimal management of patients with fibromyalgia (FM) requires a combination of non-pharmacological and pharmacological interventions. Our study aimed to analyse the effects of a supplemented physical programme on the quality of life of FM patients.
We enrolled 60 patients, all female (mean age 49±5.7 years), with primary FM (mean years of disease 33±12 months). Patients who agreed to participate in this study met the proposed 1990 American College of Rheumatology classification criteria and the 2010 American College of Rheumatology preliminary diagnostic criteria and were recruited at Policlinico P. Giaccone, University Hospital of Palermo, Italy. Thirty patients undertook a physical programme consisting of group exercises, laser and TENS treatment (Combi-group). The remaining 30 FM patients (Exonly-group) practiced only group exercise (Control group). Ten patients with mechanical pain were considered as unrelated control group disease. Fatigue, sleep dysfunction and pain were reported and evaluated before and after the treatment for each patient. Particularly, the Fibromyalgia Impact Questionnaire (FIQ), SF36 Questionnaire (SF36) and Visual analogue scale for pain and fatigue (VAS pain and fatigue) were administered at baseline (T0) and at the end of the treatment (T1) (after 40 rehabilitation sessions over 20-week).
The combined treatment significantly improved the perception of pain and fatigue and the overall quality of life. In detail, the Combi-group experienced a statistically significant improvement in FIQ but not in the SF36 after the treatment. | According to our results, an intense physical rehabilitation programme could be considered a promising essential step in the management of FM patients. |
Subsets and Splits