Search

Introduction: Degenerative diseases, such as Alzheimer's disease, heart disease and arthritis cause great suffering and are major socioeconomic burdens. An attractive treatment approach is stem cell transplantation to regenerate damaged or destroyed tissues. However, this can be problematic. For example, donor cells may not functionally integrate into the host tissue. An alternative methodology is to deliver bioactive agents, such as small molecules, directly into the diseased tissue to enhance the regenerative potential of endogenous stem cells. Areas covered: In this review, the authors discuss the necessity of developing these small molecules to treat degenerative diseases and survey progress in their application as therapeutics. They describe both the successes and caveats of developing small molecules that target endogenous stem cells to induce tissue regeneration. This article is based on literature searches which encompass databases for biomedical research and clinical trials. These small molecules are also categorized per their target disease and mechanism of action. Expert opinion: The development of small molecules targeting endogenous stem cells is a high-profile research area. Some compounds have made the successful transition to the clinic. Novel approaches, such as modulating the stem cell niche or targeted delivery to disease sites, should increase the likelihood of future successes in this field.

Purpose: Patellar dislocation can occur in isolation or be associated with chronic instability. The goals of this study are to describe the rate and factors associated with additional patellar instability events (ipsilateral recurrence and contralateral dislocation), as well as the development of patellofemoral arthritis in patients who are skeletally immature at the time of first patellar dislocation., Methods: The study included a population-based cohort of 232 skeletally immature patients who experienced a first-time lateral patellar dislocation between 1990 and 2010. A chart review was performed to collect information related to the initial injury, treatment, and outcomes. Subjects were followed for a mean of 12.1 years to determine the rate of subsequent patellar dislocation (ipsilateral recurrence or contralateral dislocation) as well as clinically significant patellofemoral arthritis., Results: 104 patients had ipsilateral recurrent patellar dislocation. The cumulative incidence of recurrent dislocation was 11% at 1 year, 21.1% at 2 years, 37.0% at 5 years, 45.1% at 10 years, 54.0% at 15 years, and 54.0% at 20 years. Patella alta (HR 10.6, 95% CI 3.6, 36.1), TT-TG ≥ 20 mm (HR 18.7, 95% CI 1.7, 228.2), and trochlear dysplasia (HR 23.7, 95% CI 1.0, 105.2) were associated with recurrence. Similarly, 18 patients (7.8%) had contralateral patellar dislocation. The cumulative incidence of patellofemoral arthritis was 0% at 2 years, 1.0% at 5 years, 2.0% at 10 years, 10.1% at 15 years, 17% at 20 years, and 39.0% at 25 years. Osteochondral injury was associated with arthritis (HR 25.7, 95% CI 6.2, 143.8). There was no association with trochler dysplasia (HR 1.2, 95% CI 0.2, 5.0), recurrent patellar instability (HR 1.2, 95% CI 0.2, 7.2), gender (HR 1.3, 95% CI 0.3, 5.6), or patellar-stabilizing surgery (HR 0.7, 95% CI 0.2, 3.5) and arthritis., Conclusion: Skeletally immature patients had a high rate of recurrent patellar instability that was associated with structural abnormalities such as patella alta,TT-TG ≥ 20 mm, and trochlear dysplasia. Approximately 10% of patients experienced a contralateral dislocation and 20% of patients developed arthritis by 20 years following initial dislocation. Osteochondral injury was associated with arthritis., Level of Evidence: Retrospective case series, Level IV.

Background: An unfavorable body composition is often present in chronic arthritis patients. This unfavorable composition is a loss of muscle mass, with a stable or increased (abdominal) fat mass. Since it is unknown when this unfavorable composition develops, we compared body composition in disease-modifying antirheumatic drugs (DMARD)-naive early arthritis patients with non-arthritis controls and explored the association, in early arthritis patients, with disease activity and traditional cardiovascular risk factors., Methods: 317 consecutive early arthritis patients (84% rheumatoid arthritis according to 2010 ACR/EULAR criteria) and 1268 age-/gender-/ethnicity-matched non-arthritis controls underwent a Dual-energy X-ray absorptiometry scan to assess fat percentage, fat mass index, fat mass distribution and appendicular lean (muscle) mass index. Additionally, disease activity, health assessment questionnaire (HAQ), acute phase proteins, lipid profile and blood pressure were evaluated., Results: Loss of muscle mass (corrected for age suspected muscle mass) was 4-5 times more common in early arthritis patients, with a significantly lower mean appendicular lean mass index (females 6% and males 7% lower, p<0.01). Patients had more fat distributed to the trunk (females p<0.01, males p = 0.07) and females had a 4% higher mean fat mass index (p<0.01). An unfavorable body composition was associated with a higher blood pressure and an atherogenic lipid profile. There was no relationship with disease activity, HAQ or acute phase proteins., Conclusion: Loss of muscle mass is 4-5 times more common in early arthritis patients, and is in early arthritis patients associated with a higher blood pressure and an atherogenic lipid profile. Therefore, cardiovascular risk is already increased at the clinical onset of arthritis making cardiovascular risk management necessary in early arthritis patients.

Purpose: Provide baseline and preliminary follow-up results in a 5-year longitudinal study of Blau syndrome., Design: Multicenter, prospective interventional case series., Methods: Baseline data from 50 patients from 25 centers worldwide, and follow-up data for patients followed 1, 2, or 3 years at the end of study enrollment. Ophthalmic data were collected at baseline and yearly visits by means of a standardized collection form., Results: Median age at onset of eye disease was 60 months and duration of eye disease at baseline 145 months. At baseline 38 patients (78%) had uveitis, which was bilateral in 37 (97%). Eight patients (21%) had moderate to severe visual impairment. Panuveitis was found in 38 eyes (51%), with characteristic multifocal choroidal infiltrates in 29 eyes (39%). Optic disc pallor in 9 eyes (12%) and peripapillary nodules in 9 eyes (12%) were the commonest signs of optic nerve involvement. Active anterior chamber inflammation was noted in 30 eyes (40%) at baseline and in 16 (34%), 17 (57%), and 11 (61%) eyes at 1, 2, and 3 years, respectively. Panuveitis was associated with longer disease duration. At baseline, 56 eyes (75%) were on topical corticosteroids. Twenty-six patients (68%) received a combination of systemic corticosteroids and immunomodulatory therapy., Conclusions: Blau uveitis is characterized by progressive panuveitis with multifocal choroiditis, resulting in severe ocular morbidity despite continuous systemic and local immunomodulatory therapy. The frequency and severity of Blau uveitis highlight the need for close ophthalmologic surveillance as well as a search for more effective therapies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The purpose of this study was to assess the long-term outcomes of radioscapholunate fusion, with and without distal pole of scaphoid excision and excision of the triquetrum. These compromised three operative groups. Seventeen patients were identified with a minimum of 10 years follow-up, with a mean of 15 years (range 10-19). Fifteen of the 17 patients were satisfied with their outcome. Two were converted to total wrist fusion. The mean outcomes scores were; pain visual analogue scale score 2.1/10, Quick Disabilities of the Arm, Shoulder, and Hand 29 and Modified Mayo Wrist score 60. Patients with excision of the triquetrum had a mean radial-ulnar arc increase of 10° compared with the other two groups, but this was not statistically significant. The mean space for the scaphocapitate joint was 1.7 mm and lunocapitate joint was 1.3 mm at latest follow-up. Close adherence to the indications and surgical technique provided a sustainable good clinical outcome. Patients who obtained a good result at 2 years were likely to achieve a good long-term outcome., Level of Evidence: IV.

Recent data suggest that the lectin-like oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1)/ox-LDL system may be involved in the pathogenesis of arthritis. We aimed to demonstrate the roles of the LOX-1/ox-LDL system in arthritis development by using LOX-1 knockout (KO) mice. Arthritis was induced in the right knees of C57Bl/6 wild-type (WT) and LOX-1 KO mice via zymosan injection. Saline was injected in the left knees. Arthritis development was evaluated using inflammatory cell infiltration, synovial hyperplasia, and cartilage degeneration scores at 1, 3, and 7 days after administration. LOX-1, ox-LDL, and matrix metalloproteinase-3 (MMP-3) expression in the synovial cells and chondrocytes was evaluated by immunohistochemistry. The LOX-1, ox-LDL, and MMP-3 expression levels in synovial cells were scored on a grading scale. The positive cell rate of LOX-1, ox-LDL, and MMP-3 in chondrocytes was measured. The correlation between the positive cell rate of LOX-1 or ox-LDL and the cartilage degeneration score was also examined. Inflammatory cell infiltration, synovial hyperplasia, and cartilage degeneration were significantly reduced in the LOX-1 KOmice with zymosan-induced arthritis (ZIA) compared to WT mice with ZIA. In the saline-injected knees, no apparent arthritic changes were observed. LOX-1 and ox-LDL expression in synovial cells and chondrocytes were detected in the knees of WT mice with ZIA. No LOX-1 and ox-LDL expression was detected in the knees of LOX-1 KOmice with ZIA or the saline-injected knees of both mice. MMP-3 expression in the synovial cells and chondrocytes was also detected in knees of both mice with ZIA, and was significantly less in the LOX-1 KO mice than in WT mice. The positive cell rate of LOX-1 or ox-LDL and the cartilage degeneration score showed a positive correlation. Our data show the involvement of the LOX-1/ox-LDL system in murine ZIA development. LOX-1-positive synovial cells and chondrocytes are potential therapeutic targets for arthritis prevention.

Autoimmune disease encompasses an array of conditions with a variety of presentations and the involvement of multiple organs. Though the etiologies of many autoimmune conditions are unclear, uncontrolled inflammatory immune response is believed to be a major cause of disease development and progression. Progranulin (PGRN), an anti-inflammatory molecule with therapeutic effect in inflammatory arthritis, was identified as an endogenous antagonist of TNFα by competitively binding to TNFR. PGRN exerts its anti-inflammatory activity through multiple pathways, including induction of T reg differentiation and IL-10 expression and inhibition of chemokine release from macrophages. In addition, the protective role of PGRN has also been demonstrated in osteoarthritis, inflammatory bowel disease, and psoriasis. Intriguingly, PGRN was reported to contribute to development of insulin resistance in high-fat diet induced diabetes. Emerging evidences indicate that PGRN may also be associated with various autoimmune diseases, including systemic lupus erythematous, systemic sclerosis, multiple sclerosis and Sjogren's syndrome. This review summarizes recent studies of PGRN as a novel target molecule in the field of autoimmune disease, and provides updated information to inspire future studies., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Monogenic autoinflammatory diseases (AIDs) are a group of inflammatory disorders induced by deregulation of the innate immune system and characterised by inflammatory bouts with fever as well as a large spectrum of other possible manifestations involving most organs and tissues. In this context, musculoskeletal manifestations represent a frequent finding in the clinical picture of patients with AIDs and may range from less severe affections including myalgia and arthralgia to severe arthritis, muscle fasciitis, bone erosions, and joint deformities. Therefore, as diagnostic suspicions originates from a careful and detailed clinical evaluation, physicians dealing with mono- genic AIDs should bear in mind their possible muscle and joint manifestations, some of which are typical and very useful for diagnostic purposes. Indeed, their prompt recognition may reduce the diagnostic delay thus allowing an early and appropriate therapeutic management. For these reasons, the present review is aimed at providing a wide overview on the different patterns of joint and muscle affections in the four main monogenic AIDs.

Arthropathy of the hand is commonly encountered. Contributing factors such as aging, trauma, and systemic illness all may have a role in the evolution of this pathology. Besides rheumatoid arthritis, other diseases affect the small joints of the hand. A review of nonrheumatoid hand arthropathies is beneficial for clinicians to recognize these problems., (Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Chikungunya virus (CHIKV), a member of Alphavirus genus, is responsible for chikungunya fever (CHIKF), which is characterized by the presence of fever, rash, myalgia, and arthralgia. Reemergence of CHIKV has become a significant public health concern in Asian and African countries and is newly emerging in the Middle East, Pacific, American, and European countries. Cytokines, innate (monocytes, natural killer cells) and adaptive immune response (role of B cells and T cells i.e. CD4 + and CD8 + ), and/or viral factors contribute to CHIKV-induced arthritis. Vector factors such as vector competence (that includes extrinsic and intrinsic factors) and effect of genome mutations on viral replication and fitness in mosquitoes are responsible for the spread of virus, although they are not directly responsible for CHIKV-induced arthritis. CHIKV-induced arthritis mimics arthritis by involving joints and a common pattern of leukocyte infiltrate, cytokine production, and complement activation. Successful establishment of CHIKV infection and induction of arthritis depends on its ability to manipulate host cellular processes or host factors. CHIKV-induced joint damage is due to host inflammatory response mediated by macrophages, T cells, and antibodies, as well as the possible persistence of the virus in hidden sites. This review provides insight into mechanisms of CHIKV-induced arthritis. Understanding the pathogenesis of CHIKV-induced arthritis will help in developing novel strategies to predict and prevent the disease in virus-infected subjects and combat the disease, thereby decreasing the worldwide burden of the disease.

Objective: The purpose of this study was to compare the stability and feasibility of four fixation constructs in a posterior column acetabular fracture: one reconstruction plate, one reconstruction plate and lag screw, two reconstruction plates, and a W-shaped acetabular angular plate., Methods: Twenty embalmed cadaveric pelvises with a posterior column acetabular fractures were allocated to one of four groups: 1) a reconstruction plate, 2) a reconstruction plate with a posterior column lag screw, 3) double reconstruction plates, and 4) a W-shaped acetabular angular plate. These constructs were mechanically loaded on a testing machine, and construct stiffness values were measured. Strain gauges were utilized to measure the mechanical behavior in the condition of compressive force., Results: Final stiffness was not different between the two reconstruction plates (445.81±98.30 N/mm) and the W-shaped acetabular angular plate (447.43±98.45 N/mm, p = 0.524), both of which were superior to a single reconstruction plate (248.90±61.95 N/mm) and a combined plate and lag screw (326.41±94.34 N/mm). Following the fixation of the W-shaped acetabular angular plate, the strain distribution was similar to the intact condition around the acetabulum. The parameters of the W-shaped acetabular angular plate that were observed at the superior region of the acetabulum were less than those of a single reconstruction plate (p<0.05), a single reconstruction plate with lag screw (p<0.05), and two reconstruction plates (p<0.05)., Conclusions: The novel W-shaped acetabular angular plate fixation technique was able to provide the biomechanically stiffest construct for stabilization of a posterior column acetabular fracture; it also resulted in a partial restoration of joint loading parameters toward the intact state.

Background: The causes and health risks associated with obesity in young people have been extensively documented, but elderly obesity is less well understood, especially in sub-Saharan Africa. This study examines the relationship between obesity and the risk of chronic diseases, cognitive impairment, and functional disability among the elderly in Ghana. It highlights the social and cultural dimensions of elderly obesity and discusses the implications of related health risks using a socio-ecological model., Methodology: We used data from wave 1 of the Ghana Study on Global Ageing and Adult Health (SAGE) survey-2007/8, with a restricted sample of 2,091 for those 65 years and older. Using random effects multinomial, ordered, and binary logit models, we examined the relationship between obesity and the risk of stage 1 and stage 2 hypertension, arthritis, difficulties with recall and learning new tasks, and deficiencies with activities of daily living and instrumental activities of daily living., Findings: Elderly Ghanaians who were overweight and obese had a higher risk of stage 1 and stage 2 hypertension, and were more likely to be diagnosed with arthritis and report severe deficiencies with instrumental activities of daily living. Those who were underweight were 1.71 times more likely to report severe difficulties with activities of daily living. A sub analysis using waist circumference as a measure of body fat showed elderly females with abdominal adiposity were relatively more likely to have stage 2 hypertension., Conclusions: These findings call for urgent policy initiatives geared towards reducing obesity among working adults given the potentially detrimental consequences in late adulthood. Future research should explore the gendered pathways leading to health disadvantages among Ghanaian women in late adulthood.

Background: Pretreatment variables have been shown to be associated with the fulfillment of patient expectations, yet in treating thumb trapeziometacarpal osteoarthritis (OA) it remains unclear how patient expectations correlate with the effectiveness of treatment. An increased understanding of the variables that affect patient expectations enables tailored patient education and patient-provider communication., Questions/purposes: (1) Is there a correlation between patient demographics and clinical characteristics, and the expectations the patients have when seeking treatment for trapeziometacarpal OA? (2) What factors are independently associated with the total expectations score and frequency of expecting "back to normal" among patients treated for trapeziometacarpal OA?, Methods: Between March 2011 and October 2013, 89 patients of all 96 eligible patients seeking treatment for trapeziometacarpal OA were approached and agreed to participate in this study. Participants completed a validated expectations survey measuring the number of expectations and the degree of improvement expected. Comparative analysis of demographic and clinical characteristics and multivariate regression analysis against patients' expectations were performed to assess and identify factors that correlate with the number and degree of expectations. Sample size was determined with an a priori power analysis (with 80% power and statistical significance set at p < 0.05), which showed that 88 patients were needed to detect the minimal clinical difference of 12 points in the Michigan Hand Questionnaire; we then increased this by 10% to allow for potential dropouts., Results: After controlling for potential confounding variables such as age, hand dominance, and work status, the following factors were associated with a higher expectations score: choice of surgery (β = 11.5; 95% CI, 0.7-23.8; p = 0.044), female gender (β = 19.0; 95% CI, 5.3-32.7; p = 0.007), and dominant side affected (β = -41.6; 95% CI, -63.7 to -19.5; p < 0.001). For the frequency of "back to normal" responses, surgical treatment (β = 7.4; 95% CI, 2.3-12.4; p = 0.005) and history of previous injury (β = 8.2; 95% CI, 0.1-16.3; p = 0.047) were independently associated factors after controlling for confounding variables. There were no independent associations with age, marital status, work status, depression or anxiety, or prior contralateral surgery., Conclusions: Patients whose dominant side was affected, were female, and chose surgical treatment, had higher total expectations. Patients who reported an antecedent injury and chose surgical treatment more frequently expected a return to normal. With identification of these factors, orthopaedic surgeons can recognize patients who are prone to higher expectations, and, thus, have the opportunity to implement efficient pretreatment education. In addition, identification of specific factors enables a focused measure of the effect of these factors on the fulfillment of expectations., Level of Evidence: Level II, prognostic study.

Temporomandibular joint (TMJ) disorders are a group of conditions that result in TMJ pain, which frequently limits basic daily activities. Experimental models that allow the study of the mechanisms underlying these inflammatory and pain conditions are of great clinical relevance. The aim of this study was to evaluate nociception, inflammation and participation of the macrophage/microglia cells in the arthritis of the TMJ induced by two phlogistic agents. 84 rats were divided into 2 groups: Zy, which received zymosan intra-articularly, or Cg, which received carrageenan intra-articularly. Mechanical nociception, total leukocyte influx to the synovial fluid and histopathological analyses were evaluated in the TMJ. The participation of macrophage/microglia located in trigeminal ganglia (TG) and in the subnucleus caudalis (V-SnC) was assessed immunohistochemically. Both agents induced mechanical hyperalgesia 6h after the induction, but a more persistent algesic state was perceived in the Cg group, which lasted for 120h. Even though both groups presented increased leukocyte influx, the Zy-group presented a more intense influx. Zymosan recruited resident macrophage in the trigeminal ganglia 24h after the injection. In the V-SnC, the group Cg presented a more prolonged immunolabeling pattern in comparison with the group Zy. It can be concluded that zymosan induced a more intense infiltrate and peripheral nervous changes, while Cg lead to a moderate TMJ inflammation with prominent changes in the V-SnC., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Post traumatic arthritis and avascular necrosis of the femoral head are common complications after operatively treated acetabular fractures. This may cause severe disabilities for the patient, necessitating a total hip arthroplasty. Even though an arthroplasty may provide good symptomatic relief, the long-term results are more uncertain and no consensus exists according to preferred prosthetic designs. With this cohort study, we aimed to investigate the medium to long term arthroplasty survival and clinical results of total hip arthroplasty after operatively treated acetabular fractures., Methods: We included 52 patients treated with a secondary total hip arthroplasty at a median of 2.4 (0.1-14.1) years after an operatively treated acetabular fracture. The median age was 54 (11-82) years. Cemented arthroplasty was used for 33 patients, 10 patients had an uncemented arthroplasty and 9 patients received a hybrid arthroplasty. Average follow up was 8.0 (SD 5.0) years., Results: Ten-year revision free arthroplasty survival was 79%. Uncemented arthroplasties had a significantly worse 10-year survival of 57%. Arthroplasties performed at a centre without a pelvic fracture service also had a significantly worse 10-years survival of 51%. Cox regression showed similar results with an 8-fold increase in risk of revision for both uncemented arthroplasties and operations performed at a non-pelvic trauma centre., Conclusion: Total hip arthroplasty secondary to an operatively treated acetabular fracture provides good symptomatic relief. These patients are, however, complex cases and are probably best treated at specialist centres with both pelvic trauma surgeons and arthroplasty surgeons proficient in complex revisions present., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: This report aimed to scrutinize the prevalence of Behçet's disease (BD)-related clinical manifestations based on age- and sex-specific subgroups using a Japanese nationwide registration database., Methods: The database of newly registered BD was obtained from the Japanese Ministry of Health, Labour and Welfare. Patients who met the International Criteria for Behçet's Disease were selected and analysed., Results: Among 6627 International Criteria for Behçet's Disease cases, 2651 (40.0%) were men and 3976 (60.0%) were women with a median age of 39 years (interquartile range: 31-50 years). Ocular lesion was more common in male [odds ratio (male: female) 2.64 (95% CI: 2.35, 2.95, P < 0.001)] and genital ulceration was more common in female (odds ratio = 0.29, 95% CI: 0.25, 0.32, P < 0.001). Ocular lesion (P < 0.001), arthritis (P < 0.001) and vascular lesions (P < 0.001) were more frequently observed in elderly registered patients. Contrarily, genital ulceration (P < 0.001), epididymitis of males (P = 0.023) and oral ulceration (P = 0.003) were more common in younger patients. Simultaneous assessment of sex and age revealed that male predominance of ocular involvement was found in the young adult generation, but not in patients over 70 year of age. A female predominance of genital ulcer was prominently observed in patients 20-59 year of age; however, the sex difference was not found in patients over 60 years of age. Sensitivity analysis using International Study Group criteria replicated the results., Conclusion: We showed that clinical phenotype in early phase of BD was different depending on onset age and sex., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Background: While glenoid retroversion and posterior humeral head decentering are common preoperative features of severely arthritic glenohumeral joints, the relationship of postoperative glenoid component retroversion to the clinical results of total shoulder arthroplasty (TSA) is unclear. Studies have indicated concern for inferior outcomes when glenoid components are inserted in 15° or more retroversion., Questions/purposes: In a population of patients undergoing TSA in whom no specific efforts were made to change the version of the glenoid, we asked whether at 2 years after surgery patients having glenoid components implanted in 15° or greater retroversion had (1) less improvement in the Simple Shoulder Test (SST) score and lower SST scores; (2) higher percentages of central peg lucency, higher Lazarus radiolucency grades, higher mean percentages of posterior decentering, and more frequent central peg perforation; or (3) a greater percentage having revision for glenoid component failure compared with patients with glenoid components implanted in less than 15° retroversion., Methods: Between August 24, 2010 and October 22, 2013, information for 201 TSAs performed using a standard all-polyethylene pegged glenoid component were entered in a longitudinally maintained database. Of these, 171 (85%) patients had SST scores preoperatively and between 18 and 36 months after surgery. Ninety-three of these patients had preoperative radiographs in the database and immediate postoperative radiographs and postoperative radiographs taken in a range of 18 to 30 months after surgery. Twenty-two patients had radiographs that were inadequate for measurement at the preoperative, immediate postoperative, or latest followup time so that they could not be included. These excluded patients did not have substantially different mean age, sex distribution, time of followup, distribution of diagnoses, American Society of Anesthesiologists class, alcohol use, smoking history, BMI, or history of prior surgery from those included in the analysis. Preoperative retroversion measurements were available for 11 (11 shoulders) of the 22 excluded patients. For these 11 shoulders, the mean (± SD) retroversion was 15.8° ± 14.6°, five had less than 15°, and six had more than 15° retroversion. We analyzed the remaining 71 TSAs, comparing the 21 in which the glenoid component was implanted in 15° or greater retroversion (mean ± SD, 20.7° ± 5.3°) with the 50 in which it was implanted in less than 15° retroversion (mean ± SD, 5.7° ± 6.9°). At the 2-year followup (mean ± SD, 2.5 ± 0.6 years; range, 18-36 months), we determined the latest SST scores and preoperative to postoperative improvement in SST scores, the percentage of maximal possible improvement, glenoid component radiolucencies, posterior humeral head decentering, and percentages of shoulders having revision surgery. Radiographic measurements were performed by three orthopaedic surgeons who were not involved in the care of these patients. The primary study endpoint was the preoperative to postoperative improvement in the SST score., Results: With the numbers available, the mean (± SD) improvement in the SST (6.7 ± 3.6; from 2.6 ± 2.6 to 9.3 ± 2.9) for the retroverted group was not inferior to that for the nonretroverted group (5.8 ± 3.6; from 3.7 ± 2.5 to 9.4 ± 3.0). The mean difference in improvement between the two groups was 0.9 (95% CI, - 2.5 to 0.7; p = 0.412). The percent of maximal possible improvement (%MPI) for the retroverted glenoids (70% ± 31%) was not inferior to that for the nonretroverted glenoids (67% ± 44%). The mean difference between the two groups was 3% (95% CI, - 18% to 12%; p = 0.857). The 2-year SST scores for the retroverted (9.3 ± 2.9) and the nonretroverted glenoid groups (9.4 ± 3.0) were similar (mean difference, 0.2; 95% CI, - 1.1 to 1.4; p = 0.697). No patient in either group reported symptoms of subluxation or dislocation. With the numbers available, the radiographic results for the retroverted glenoid group were similar to those for the nonretroverted group with respect to central peg lucency (four of 21 [19%] versus six of 50 [12%]; p = 0.436; odds ratio, 1.7; 95% CI, 0.4-6.9), average Lazarus radiolucency scores (0.5 versus 0.7, Mann-Whitney U p value = 0.873; Wilcoxon rank sum test W = 512, p value = 0.836), and the mean percentage of posterior humeral head decentering (3.4% ± 5.5% versus 1.6% ± 6.0%; p = 0.223). With the numbers available, the percentage of patients with retroverted glenoids undergoing revision (0 of 21 [0%]) was not inferior to the percentage of those with nonretroverted glenoids (three of 50; [6%]; p = 0.251)., Conclusion: In this small series of TSAs, postoperative glenoid retroversion was not associated with inferior clinical results at 2 years after surgery. This suggests that it may be possible to effectively manage arthritic glenohumeral joints without specific attempts to modify glenoid version. Larger, longer-term studies will be necessary to further explore the results of this approach., Level of Evidence: Level III, therapeutic study.

Grip strength deficit is a measure of pain-induced functional disability in rheumatic disease. We tested whether this parameter and tactile allodynia, the standard pain measure in preclinical studies, show parallels in their response to analgesics and basic mechanisms. Mice with periarticular injections of complete Freund's adjuvant (CFA) in the ankles showed periarticular immune infiltration and synovial membrane alterations, together with pronounced grip strength deficits and tactile allodynia measured with von Frey hairs. However, inflammation-induced tactile allodynia lasted longer than grip strength alterations, and therefore did not drive the functional deficits. Oral administration of the opioid drugs oxycodone (1-8 mg/kg) and tramadol (10-80 mg/kg) induced a better recovery of grip strength than acetaminophen (40-320 mg/kg) or the nonsteroidal antiinflammatory drugs ibuprofen (10-80 mg/kg) or celecoxib (40-160 mg/kg); these results are consistent with their analgesic efficacy in humans. Functional impairment was generally a more sensitive indicator of drug-induced analgesia than tactile allodynia, as drug doses that attenuated grip strength deficits showed little or no effect on von Frey thresholds. Finally, ruthenium red (a nonselective TRP antagonist) or the in vivo ablation of TRPV1-expressing neurons with resiniferatoxin abolished tactile allodynia without altering grip strength deficits, indicating that the neurobiology of tactile allodynia and grip strength deficits differ. In conclusion, grip strength deficits are due to a distinct type of pain that reflects an important aspect of the human pain experience, and therefore merits further exploration in preclinical studies to improve the translation of new analgesics from bench to bedside., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Total ankle arthroplasty (TAA) is an alternative to arthrodesis, but no randomized trial has examined whether a fixed bearing or mobile bearing implant provides improved gait mechanics., Questions/purposes: We wished to determine if fixed- or mobile-bearing TAA results in a larger improvement in pain scores and gait mechanics from before surgery to 1 year after surgery, and to quantify differences in outcomes using statistical analysis and report the standardized effect sizes for such comparisons., Methods: Patients with end-stage ankle arthritis who were scheduled for TAA between November 2011 and June 2013 (n = 40; 16 men, 24 women; average age, 63 years; age range, 35-81 years) were prospectively recruited for this study from a single foot and ankle orthopaedic clinic. During this period, 185 patients underwent TAA, with 144 being eligible to participate in this study. Patients were eligible to participate if they were able to meet all study inclusion criteria, which were: no previous diagnosis of rheumatoid arthritis, a contralateral TAA, bilateral ankle arthritis, previous revision TAA, an ankle fusion revision, or able to walk without the use of an assistive device, weight less than 250 pounds (114 kg), a sagittal or coronal plane deformity less than 15°, no presence of avascular necrosis of the distal tibia, no current neuropathy, age older than 35 years, no history of a talar neck fracture, or an avascular talus. Of the 144 eligible patients, 40 consented to participate in our randomized trial. These 40 patients were randomly assigned to either the fixed (n = 20) or mobile bearing implant group (n = 20). Walking speed, bilateral peak dorsiflexion angle, peak plantar flexion angle, sagittal plane ankle ROM, peak ankle inversion angle, peak plantar flexion moment, peak plantar flexion power during stance, peak weight acceptance, and propulsive vertical ground reaction force were analyzed during seven self-selected speed level walking trials for 33 participants using an eight-camera motion analysis system and four force plates. Seven patients were not included in the analysis owing to cancelled surgery (one from each group) and five were lost to followup (four with fixed bearing and one with mobile bearing implants). A series of effect-size calculations and two-sample t-tests comparing postoperative and preoperative increases in outcome variables between implant types were used to determine the differences in the magnitude of improvement between the two patient cohorts from before surgery to 1 year after surgery. The sample size in this study enabled us to detect a standardized shift of 1.01 SDs between group means with 80% power and a type I error rate of 5% for all outcome variables in the study., Results: This randomized trial did not reveal any differences in outcomes between the two implant types under study at the sample size collected. In addition to these results, effect size analysis suggests that changes in outcome differ between implant types by less than 1 SD. Detection of the largest change score or observed effect (propulsive vertical ground reaction force [Fixed: 0.1 ± 0.1; 0.0-1.0; Mobile: 0.0 ± 0.1; 0.0-0.0; p = 0.0.051]) in this study would require a future trial to enroll 66 patients. However, the smallest change score or observed effect (walking speed [Fixed: 0.2 ± 0.3; 0.1-0.4; Mobile: 0.2 ± 0.3; 0.0-0.3; p = 0.742]) requires a sample size of 2336 to detect a significant difference with 80% power at the observed effect sizes., Conclusions: To our knowledge, this is the first randomized study to report the observed effect size comparing improvements in outcome measures between fixed and mobile bearing implant types. This study was statistically powered to detect large effects and descriptively analyze observed effect sizes. Based on our results there were no statistically or clinically meaningful differences between the fixed and mobile bearing implants when examining gait mechanics and pain 1 year after TAA., Level of Evidence: Level II, therapeutic study.

This study evaluated the feasibility and effectiveness of translating the evidence-based program, Fit & Strong!, into a Spanish program, ¡En Forma y Fuerte!. A single-group, quasi-experimental design (n = 34, mean age = 58.8 [8.1], 87.2% female, 87.2% reported speaking mostly Spanish) was used to assess implementation feasibility and the impact of ¡En Forma y Fuerte! on arthritis-related outcomes in Hispanics with arthritis. Significant improvements in lower-extremity strength, perceived physical function, and pain were observed from baseline to 8 weeks (p < .05); these improvements were maintained at 6 months. Significant improvements in aerobic endurance and stiffness were observed from baseline to 6 months (p < .05). No major program adaptations (other than language) were observed or reported. However, the instructors provided several suggestions for program improvements, including adjusting the literacy level and length of the program. Findings suggest ¡En Forma y Fuerte! is feasible and effective, potentially providing a much-needed program for older Hispanics with arthritis.

Objective: To examine the association between arthritis diagnosis and education and employment participation among young adults, and to determine whether findings differ by self-rated health and age., Methods: Data from the National Health Interview Survey, in the years 2009-2015, were combined and analyzed. The study sample was restricted to those ages 18-29 years, either diagnosed with arthritis (n = 1,393) or not (n = 40,537). The prevalence and correlates of employment and education participation were compared by arthritis status. Demographic characteristics, social role participation restrictions, health factors, and health system use variables were included as covariates. Models were stratified for age (18-23 versus 24-29 years) and self-rated health. Weighted proportions and univariate and multivariate associations were calculated to examine the association between arthritis and education and employment participation., Results: Respondents with arthritis were more likely to be female, married, and report having more social participation restrictions, fair/poor health, and more functional limitations than those without arthritis. In multivariate models, arthritis was significantly associated with lower education (prevalence ratio [PR] 0.75 [95% confidence interval (95% CI) 0.57-0.98]) and higher employment participation (PR 1.07 [95% CI 1.03-1.13]). Additional stratified analyses indicated an association between arthritis diagnosis and greater employment participation in those ages 18-23 years and reporting higher self-rated health., Conclusion: Young adults with arthritis may be transitioning into employment at an earlier age than their peers without arthritis. To inform the design of interventions that promote employment participation, future research on the education and employment experiences of young adults with arthritis is needed., (© 2016, American College of Rheumatology.)

Introduction: We have limited knowledge about the underlying disease mechanisms and causes of pain in hand osteoarthritis (OA). Consequently, no disease-modifying drug exists, and more knowledge about the pathogenesis of hand OA is needed, as well as a validation of different outcome measures. Our first aim of this study is to explore the validity of various imaging modalities for the assessment of hand OA. Second, we want to gain a better understanding of the disease processes, with a special focus on pain mechanisms., Methods and Analysis: The Nor-Hand study is a hospital-based observational study including 300 patients with evidence of hand OA by ultrasound and/or clinical examination. The baseline examination consists of functional tests and joint assessment of the hands, medical assessment, pain sensitisation tests, ultrasound (hands, acromioclavicular joint, hips, knees and feet), CT and MRI of the dominant hand, conventional radiographs of the hands and feet, fluorescence optical imaging of the hands, collection of blood and urine samples as well as self-reported demographic factors and OA-related questionnaires. Two follow-up examinations are planned. Cross-sectional analyses will be used to investigate agreements and associations between different relevant measures at the baseline examination, whereas the longitudinal data will be used for evaluation of predictors for clinical outcomes., Ethics and Dissemination: The protocol is approved by the Norwegian Regional Committee for Medical and Health Research Ethics (Ref. no: 2014/2057). The participants receive oral and written information about the project and sign a consent form before participation. They can, whenever they want, withdraw from the study, and all de-identified data will be safely stored on the research server at Diakonhjemmet Hospital. Results will be presented at international and national congresses and in peer-reviewed rheumatology journals., Trial Registration Number: NCT03083548; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: To conduct a comprehensive analysis of cytokine concentrations in sera and mononuclear cell supernatants in order to examine inter- and intra-individual cytokine variations in undifferentiated arthritis progressing to rheumatoid arthritis and healthy control groups., Methods: Patients with UA (undifferentiated arthritis) developing RA (rheumatoid arthritis) (UA→RA) (n=16) and healthy controls (n=16) were enrolled into the study. UA→RA patients were followed up for six months since the final RA diagnosis. Cytokines IFN-γ, IL-10, TNF, IL-17A, IL-6, IL-1β, IL-2 in sera and mononuclear cell supernatants in 72h and 120h culture variants with- and without anti-CD3 stimulations were assayed using flow cytometric bead array., Results: The cytokine profile of UA→RA differs from the healthy individual cytokine profile. It is possible to observe specific cytokine pattern characterizing each patient, which alters during course of disease. Specifically, we can distinguish three UA→RA cohorts: the group of patients susceptible to the therapy, characterized by the drop of cytokine levels between 1st and 3rd visit with visible decrease of cytokines in 2nd visit and then secondary slighter increase in 3rd visit; the group of patients refractory or clinically worsening on the therapy, characterized by the highest cytokine levels at 2nd visit with secondary decrease in 3rd visit; and the group of patients with variable responses to the therapy without any specific common cytokine pattern. The cytokine patterns in supernatants of PBMC stimulated anti-CD3 for 72h and 120h are very similar., Conclusions: The personal profile including multiplexed cytokine patterns in serum and supernatant may be potentially used for optimization of therapy introduction and monitoring., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose of Review: Polyarthritis can have numerous reasons and may thus constitute a challenge for differential diagnosis. One rare potential reason for sterile polyarthritis is underlying pancreatic disease with systemic hyperlipasemia, most often accompanied by painful skin lesions caused by a subcutaneous inflammatory process known as panniculitis. Systematic evidence on pancreatic panniculitis and polyarthritis is limited, particularly regarding its feature as facultative paraneoplasia with underlying intra- or even extra-pancreatic malignancy. Therefore, we will summarize the current knowledge about this orphan disease including epidemiological, pathophysiological, diagnostic, and treatment aspects in the present review., Recent Findings: Although direct evidence is lacking, it is highly probable that pancreatic polyarthritis and panniculitis are caused by peripheral lipolytic activity of lipase systemically circulating due to benign (e.g., acute or chronic pancreatitis) or malign (e.g., acinar cell carcinoma (ACC) or adenocarcinoma) pancreatic disease. In the latter case, pancreatic polyarthritis and panniculitis are associated with poor outcome. Pancreatic polyarthritis and panniculitis should always be included into diagnostic considerations, and once suspected, a thorough work-up to identify the underlying disease has to be performed.

TNF-α plays a key role in the development of rheumatoid arthritis (RA) and inflammatory bone loss. Unfortunately, treatment of RA with anti-inflammatory glucocorticoids (GCs) also causes bone loss resulting in osteoporosis. Our previous studies showed that overexpression of glucocorticoid-induced leucine zipper (GILZ), a mediator of GC's anti-inflammatory effect, can enhance osteogenic differentiation in vitro and bone acquisition in vivo. To investigate whether GILZ could antagonize TNF-α-induced arthritic inflammation and protect bone in mice, we generated a TNF-α-GILZ double transgenic mouse line (TNF-GILZ Tg) by crossbreeding a TNF-α Tg mouse, which ubiquitously expresses human TNF-α, with a GILZ Tg mouse, which expresses mouse GILZ under the control of a 3.6kb rat type I collagen promoter fragment. Results showed that overexpression of GILZ in bone marrow mesenchymal stem/progenitor cells protected mice from TNF-α-induced inflammatory bone loss and improved bone integrity (TNF-GILZ double Tg vs. TNF-αTg, n = 12-15). However, mesenchymal cell lineage restricted GILZ expression had limited effects on TNF-α-induced arthritic inflammation as indicated by clinical scores and serum levels of inflammatory cytokines and chemokines.

Purpose: Common variable immunodeficiency (CVID) is a complex, heterogeneous immunodeficiency characterized by hypogammaglobulinemia, recurrent infections, and poor antibody response to vaccination. While antibiotics and immunoglobulin prophylaxis have significantly reduced infectious complications, non-infectious complications of autoimmunity, inflammatory lung disease, enteropathy, and malignancy remain of great concern. Previous studies have suggested that CVID patients diagnosed in childhood are more severely affected by these complications than adults diagnosed later in life. We sought to discern whether the rates of various infectious and non-infectious conditions differed between pediatric-diagnosed (ages 17 or younger) versus adult-diagnosed CVID (ages 18 or older)., Methods: Using the United States Immunodeficiency Network (USIDNET) database, we performed a retrospective analysis of 457 children and adults with CVID, stratified by age at diagnosis. Chi-squared testing was used to compare pediatric versus adult groups., Results: After correcting for multiple comparisons, we identified few statistically significant differences (p ≤ 0.0004) between pediatric and adult groups. Pediatric-onset CVID patients had more frequent diagnoses of otitis media, developmental delay, and failure to thrive compared with adult-onset CVID patients. Adult CVID patients were more frequently diagnosed with bronchitis, arthritis, depression, and fatigue. Diagnoses of autoimmunity, lymphoma, and other malignancies were higher in adults but not to a significant degree. Serum immunoglobulins (IgG, IgA, and IgM) and lymphocyte subsets did not differ significantly between the two groups. When complications of infections and co-morbid conditions were viewed categorically, there were few differences between pediatric-onset and adult-onset CVID patients., Conclusions: These results suggest that pediatric CVID is not a distinct phenotype. Major features were comparable across the groups. This study underscores the need for continued longitudinal study of pediatric and early-onset CVID patients to further characterize accrual of features over time.

IL-17 is a pro-inflammatory cytokine implicated a variety of autoimmune diseases. We have recently reported that FGF2 cooperates with IL-17 to protect intestinal epithelium during dextran sodium sulfate (DSS)-induced colitis. Here, we report a pathogenic role of the FGF2-IL-17 cooperation in the pathogenesis of autoimmune arthritis. Combined treatment with FGF2 and IL-17 synergistically induced ERK activation as well as the production of cytokines and chemokines in human synovial intimal resident fibroblast-like synoviocytes (FLS). Furthermore, ectopic expression of FGF2 in mouse joints potentiated IL-17-induced inflammatory cytokine and chemokine production in the tissue. In the collagen-induced arthritis (CIA) model, while ectopic expression of FGF2 in vivo exacerbated tissue inflammation and disease symptom in the wild-type controls, the effect was largely blunted in Il17a -/- mice. Taken together, our study suggests that FGF2 cooperates with IL-17 to promote the pathogenesis of autoimmune arthritis by cooperating with IL-17 to induce inflammatory response.

Objective: To determine major symptoms and signs in patients of systemic lupus erythematosus., Methods: This cross-sectional study was conducted at the Lady Reading Hospital, Khyber Teaching Hospital and Hayatabad Medical Complex, Peshawar, Pakistan, from January 15, 2014, to August 15, 2016, and comprised patients of systemic lupus erythematosus. Data was collected through an interview-based questionnaire containing questions about different symptoms. SPSS 20 was used for data analysis., Results: Of the 663 patients, 606(91.4%) were females and 57(8.6%) males. The overall mean age of patients was 33.09 ± 12.40 years and the mean age of diagnosis was 31.85 ± 12.40 years. The most common general symptom in our study was fatigue which was present in 524(79.03%) patients. Other constitutional symptoms were fever 334(50.04%), body aches 443(66.08%) and weakness 411(62%). The most common clinical manifestation in our study was arthritis 518(78.1%). Malar rash was found in 487(73.5%) patients. Dry eye was in 227(34.2%) patients, followed by conjunctivitis 156(23.5%). Anaemia was present in 444(66.96%) patients, followed by leukopenia 166(25.03%) and thrombocytopenia 42(6.33%)., Conclusions: Significant regional differences existed in the clinical manifestations of systemic lupus erythematosus in Khyber Pakhtunkhwa compared to other regions.

Alarmins are endogenous molecules with homeostatic roles that have reached the focus of research in inflammatory arthritis in the last two decades, mostly due to their ability to indicate tissue related damage after active or passive release from injured cells. From HMGB1, S100A8/A9 and S100A12 proteins, over heat-shock proteins (HSPs) and purine metabolites (e.g. uric acid, ATP) to altered matrix proteins and interleukin-33 (IL-33), a number of alarmins have been determined until now as having a role in rheumatoid arthritis, psoriatic and juvenile idiopathic arthritis, as well as spondyloarthritis and gout. Although formerly being linked to initiation and chronification of inflammatory arthritis, driving auto- and paracrine inflammatory loops, more recent research has also unraveled the alarmins' role in the crosstalk between innate and adaptive immunity and in resolution of inflammation. Providing a state-of-the-art overview of known alarmins, this review lists the known modes of action and pathologic contribution of alarmins to inflammatory arthritis, as well as biomarker potential of alarmins in the clinical setting for tracking disease severity. Based upon research on animal experimental models (CIA, AIA) and clinical trials, a look is made into potentially viable strategies for modifying alarmin secretion and their target receptor (e.g. TLR, RAGE) interaction with the purpose of attenuating arthritic disease., (Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Preclinical and clinical studies using cannabis-based therapy have been shown to provide both analgesia and anti-inflammatory effects, with an overall alleviation of clinical symptoms in animal models of arthritis, highlighting its promising therapeutic application for humans. Despite this, the development of cannabis-based therapeutics remains in its infancy, with further investigation into its efficacy and safety profile in patients still required. This synopsis reviews the various components of the endocannabinoid system in health and disease and their potential as therapeutic targets., (© 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Approaches providing the positioning of human amniotic membrane (HAM) within the intra-articular space of arthritic TMJs have never been investigated. This contrasts with the increasing amount of evidence suggesting the potential positive effects of HAM on a number of surgical conditions, even included the interpositional arthroplasty for TMJ ankylosis. Thus, the possible usefulness of HAM to restore joint functions in severely damaged TMJs could be hypothesized. Based on these premises, the clinical research question "Is human amniotic membrane positioning effective to reduce symptoms and restore jaw function in patients with severe inflammatory-degenerative disorders of the temporomandibular joint?" has been addressed by performing a systematic review of the literature. Out of potential 11988 and 8883 citations in the PubMed and Scopus databases, respectively, only five were of possible interest for inclusion in the review, but none of them addressed specifically the clinical research question. Thus, the hypothetical background for usefulness was discussed. The benefits of HAM positioning in TMJs with severe inflammatory-degenerative disorders could be related with its anti-inflammatory and anti-microbial and analgesic properties as well as its low immunogenicity. Studies in which HAM is positioned within the joint space of patients with severe TMJ degeneration, either as a disc-replacing film during major surgeries for discectomy and arthroplasty or as an injectable solution that can be needle-inserted after an arthrocentesis procedure, should be designed to test the hypothesis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Bowel inflammation is closely linked to chronic joint inflammation. Research reported in the 1980s demonstrated bowel inflammation with gross and microscopic pathological features identical to those of Crohn's disease in over 60% of patients with spondyloarthritis (SpA). Numerous prospective studies have evidenced joint involvement in patients with chronic inflammatory bowel disease (IBD) and bowel inflammation in patients with SpA. Nevertheless, the interactions of joint disease and chronic bowel inflammation remain incompletely elucidated. Two main hypotheses have been suggested to explain potential links between inflammation of the mucosal immune system and peripheral arthritis: one identifies gut bacteria as potentially implicated in the development of joint inflammation and the other involves the recruitment of gut lymphocytes or activated macrophages to the joints. Pathophysiological investigations have established that HLA-B27 is a pivotal pathogenic factor. Here, we review current data on links between chronic bowel inflammation and inflammatory joint disease., (Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Introduction: In arthritis, inflammatory processes are triggered by numerous factors that are released from joint tissues, promoting joint destruction and pathological progression. During inflammation, a novel family of pro-inflammatory molecules called alarmins is released, amplifying inflammation and joint damage. Areas covered: With regard to the role of the alarmins S100A8 and S100A9 in the pathogenesis of arthritis, recent advances and the future prospects in terms of therapeutic implications are considered. Expert opinion: There is still an urgent need for novel treatment strategies addressing the local mechanisms of joint inflammation and tissue destruction, offering promising therapeutic alternatives. S100A8 and S100A9, which are the most up-regulated alarmins during arthritis, are endogenous triggers of inflammation, defining these proteins as promising targets for local suppression of arthritis. In murine models, the blockade of S100A8/S100A9 ameliorates inflammatory processes, including arthritis, and there are several lines of evidence that S100-alarmins may already be targeted in therapeutic approaches in man.

Arthritis secondary to invasive meningococcemia is rare and has been described as a direct result of bacteremia or as immunoallergic-type arthritis, related to the immune complex. Only a few case series have been reported.This multicenter study aimed to describe the clinical characteristics and therapeutic outcomes of arthritis secondary to meningococcal infection.We performed a 5-year retrospective study. We included all patients with inflammatory joint symptoms and proven meningococcal disease defined by the identification of Neisseria meningitidis in blood, cerebrospinal fluid, or synovial fluid. Septic arthritis was defined by the identification of N meningitidis in joint fluid. Immune-mediated arthritis was considered to be arthritis occurring after at least 1 day of invasive meningococcal disease without positive joint fluid culture.A total of 7 patients (5 males) with joint symptoms and meningococcal disease were identified. The clinical presentation was mainly oligoarticular and the knee was the most frequent joint site. Five patients had septic arthritis and 4 had immune-mediated arthritis; 2 had septic arthritis followed by immune-mediated arthritis. Immune-mediated arthritis occurred 3 to 7 days after meningococcal meningitis, and treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) led to improvement without complications.Physicians must be vigilant to the different clinical presentations in patients with arthritis associated with invasive meningococcal disease. If immune-mediated arthritis is suspected, NSAIDs are usually efficient.

Background: Nocturnal leg cramps (NLC) are common and poorly understood., Objective: To determine the prevalence of NLC and associations with cardiometabolic, sleep, and behavioral risk factors in the US population., Design: Cross-sectional epidemiology., Participants: National Health and Nutrition Examination Survey, 2005-2006 and 2007-2008 waves., Main Outcome(s) and Measure(s): NLC were assessed with, "In the past month, how often did you have leg cramps while trying to sleep?" Responses were categorized as None, Mild, or Moderate-Severe. Demographics, medical history, sleep disturbances, and cardiometabolic risk factors were evaluated using the 2005-2006 dataset. Variables that demonstrated significant relationships to NLC after adjusting for age, sex, education, and BMI were assessed in the 2007-2008 dataset. Variables that were still significant were entered into a forward stepwise regression model combining both waves, to determine which variables best explained the variance in NLC., Results: Prevalence was 24-25% reporting mild and 6% reporting moderate-severe NLC. NLC increased with age, lower education, unemployment, shorter sleep duration, all assessed sleep symptoms (nocturnal "leg jerks", snoring, snorting/gasping, difficulty falling asleep, difficulty maintaining sleep, non-restorative sleep, sleepiness, use of sleep medications), higher BMI, smoking, medical history (hypertension, heart failure, angina, stroke, arthritis, respiratory disease, and cancer), depression symptoms, and biomarkers (CRP, HbA1c, calcium, cadmium, red blood cells). Stepwise analysis showed that moderate-severe nocturnal leg cramps were associated with (in decreasing order of partial R2): leg jerks, poor overall health, arthritis, difficulty falling asleep, age, nonrestorative sleep, red blood cell count, lower education, angina, and difficulty maintaining sleep., Conclusions and Relevance: Based on this first large, representative study, NLC occurring >5x per month are reported by 6% of the adult US population. Sleep disturbance symptoms and health conditions are associated with higher frequency of NLC, suggesting that NLC is a marker, and possibly contributor, to poor sleep and general health.

Background: Total ankle arthroplasty (TAA) is becoming an increasingly utilized procedure for the management of end-stage ankle arthritis. Elderly patients are the fastest growing segment of the population in the western world, creating a unique challenge to the health economics of our era. Determining if elderly patients with end-stage ankle arthritis demonstrate the same improvements in clinical outcomes and functional measures of gait following TAA would be valuable. This can aid to evaluate the utilization of TAA in this enlarging cohort of our population., Methods: Consecutive series of twenty-one patients over the age of 70, who underwent TAA for end-stage ankle arthritis, was prospectively compared to a series of twenty-one patients aged 50-60, who underwent the same procedure by single surgeon during same time period. Clinical outcomes were measured with outcome scores including VAS pain score, AOFAS Ankle and Hindfoot Score, and the SF-36. Three-dimensional gait analysis was performed preoperatively and at a minimum of one year postoperatively, to measure temporal-spatial, kinematic, and kinetic parameters of gait. Mixed model multivariate statistical analysis was used to evaluate and compare the independent contributions to outcomes of the surgical intervention over time; of patient age; and of time-plus-age interaction, as these influenced both the clinical outcomes and the functional gait outcomes., Results: Statistically significant improvements in VAS pain scores, AOFAS ankle/hindfoot scores, and SF-36 scores were demonstrated in both age groups. Following surgery, there were improvements in all parameters of gait, including temporal-spatial parameters as step length and walking velocity; kinematic parameters, including, increase in total range of motion to a total of 17-19°; and kinetic parameters, including increase in ankle power and moment. The improvements both in clinical and gait outcomes were equivalent in the two age groups., Conclusions: In this comparative study, it is shown that both elderly patients over the age of 70 and younger patients aged 50-60 demonstrated equivalent improvements clinical and gait outcomes following ankle arthroplasty. This may be important data both for clinical decision-making and the health economics for our ageing population., (Copyright © 2016 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

Purpose: To determine the microstructure of the fovea in patients with Stickler syndrome using imaging by spectral-domain optical coherence tomography (SD OCT) and swept-source OCT., Design: Retrospective case series study., Participants: A total of 39 eyes of 25 patients with genetically confirmed Stickler syndrome were studied., Methods: All of the patients had mutations in the COL2A1 gene and were diagnosed with Stickler syndrome. Cross-sectional OCT images, OCT angiography (OCTA), and en face OCT images were assessed. The ratio of the foveal inner retinal layer (fIRL) thickness to the parafoveal inner retinal layer (pIRL) thickness, the ratio of the foveal outer retinal layer (fORL) thickness to the parafoveal outer retinal layer (pORL) thickness, and the size of the foveal avascular zone (FAZ) were determined., Main Outcome Measures: The degree of foveal hypoplasia and the best-corrected visual acuity in patients with Stickler syndrome., Results: A persistence of the inner retinal layers in the fovea with an fIRL/pIRL ratio >0.2 was present in 32 of the 39 eyes (82%). Optical coherence tomography angiography showed that the FAZ was smaller, 0 to 0.19 mm 2 , than that of normal eyes, in 25 eyes of 17 patients who underwent OCTA. There was no significant correlation between the visual acuities and the fIRL/pIRL ratios., Conclusions: A mild foveal hypoplasia with a persistence of the IRL is characteristic of eyes with Stickler syndrome. The visual acuities were not correlated with the fIRL/pIRL ratios., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aim: It has been reported in the literature that patients with poor preoperative mental health are more likely to have worse functional outcomes following primary total hip and knee arthroplasty. We could find no studies investigating whether preoperative mental health also affects length of hospital stay following surgery. The aim of this study was to determine whether preoperative mental health affects length of hospital stay and long-term functional outcomes following primary total hip and knee arthroplasty. We also aimed to determine whether mental health scores improve after arthroplasty surgery and, finally, we looked specifically at a subgroup of patients with diagnosed mental illness to determine whether this affects length of hospital stay and functional outcomes after surgery., Method: Through a review of prospectively collected regional joint registry data, we compared preoperative mental health scores (SF-12 MH) with length of hospital stay and post-operative (1 and 5 years) functional outcome scores (Oxford and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)) in 2279 primary total hip and knee arthroplasty surgeries performed in the Bay of Plenty District Health Board between 2006 and 2010., Results: Based on Pearson product-moment correlation coefficients, there was a significant correlation between preoperative mental health scores and post-operative Oxford scores at 1 year as well as post-operative WOMAC scores at both 1 and 5 years. There was no significant correlation between preoperative mental health and length of hospital stay. Mental health scores improved significantly after arthroplasty surgery. Those patients with a formally diagnosed mental illness had significantly worse preoperative mental health and function scores. Following surgery, they had longer hospital stays although their improvement in function was not significantly different to those without mental illness., Conclusion: The results of this study support reports in the literature that there is a correlation between preoperative mental health and long-term functional outcomes following primary total hip and knee arthroplasty. Patients with poor preoperative mental health are more likely to have worse functional outcomes at 1 and 5 years following surgery. No correlation between preoperative mental health and length of hospital stay was identified. Mental health scores improved significantly after surgery. Patients with mental illness had longer hospital stays and despite worse preoperative mental health and function had equal improvements in functional outcomes.

Objective: To investigate the prevalence of conduction disorders in patients with early arthritis and the relationship with inflammation and traditional cardiovascular (CV) risk factors., Methods: Patients with rheumatoid arthritis (RA) have a 2-fold higher risk of sudden cardiac death, possibly owing to conduction disorders. This increased risk might already be present at the clinical onset of arthritis. Therefore, we assessed electrocardiography, blood pressure, 28-joint Disease Activity Score (DAS28), lipid profile, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level in 480 patients with early arthritis at baseline and after 1 year., Results: The prevalence of conduction disorders was 12.5%. Conduction times at baseline were not associated with DAS28, ESR, or CRP levels and did not change during antirheumatic treatment. Baseline and the improvement in DAS28 (European League Against Rheumatism response), ESR, and CRP were significantly associated with heart rate, lipid profile, and blood pressure. Elevated total cholesterol and blood pressure were associated with an increased QRS time. The change in heart rate differed 7.3 bpm between patients with the least versus largest DAS improvement., Conclusion: The prevalence of conduction disorders in patients with early arthritis was 12.5%, which is similar to the general population and was not associated with changes in inflammation markers. However, a high cholesterol was associated with a prolonged QRS time. Therefore, the emphasis of CV risk management in arthritis should not be only on treatment of disease activity but also on traditional CV risk factors. The relationship between the improvement in disease activity and heart rate is remarkable because this could imply a 10-year CV mortality risk difference of 24%.

Monoarticular arthritis is inflammation characterized by joint pain, swelling, and sometimes periarticular erythema. Although chronic causes are seen, the onset is often acute. An infected joint can quickly lead to permanent damage, making it a medical emergency. However, acute gout presenting as monoarticular arthritis is often so uncomfortable it requires urgent attention. Monoarticular crystalline arthritis is common and a septic joint is a medical emergency so it is no surprise that these diagnoses come to mind with complaint of inflammation in 1 joint. However, there are many causes of monoarticular arthritis that clinicians must consider., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The development of valgus tibiotalar tilt following hindfoot arthrodesis is rarely discussed in the literature. The purpose of this study was to determine the incidence of valgus tibiotalar tilt and to evaluate if there were any radiographic predictors for the development of valgus tibiotalar tilt., Methods: Patients who underwent hindfoot fusion between January 1, 2004 and December 31, 2013 were identified. Charts were reviewed for demographic information and operative details. Preoperative and postoperative radiographs were reviewed for the development of tibiotalar tilt, and standardized measurements and angles were calculated. A total of 187 patients were included. There were 106 (56.7%) females and 81 (43.3%) males. The average age was 52 years (range, 11-82 years). The most common indication for surgery was adult-acquired flatfoot deformity (n = 92, 49.2%), followed by arthritis (n = 83, 44.4%). The most common procedure was triple arthrodesis (n = 101, 54%). Twenty-seven patients demonstrated tibiotalar tilt preoperatively., Results: A total of 51 patients (27.3%) developed valgus tibiotalar tilt postoperatively at an average of 3.6 months after surgery. We found that an increase in the preoperative Meary (lateral talar-first metatarsal) angle (hazard ratio, 1.039; 95% confidence interval, 1.002-1.077; P < .05) was associated with the development of tibiotalar tilt. An increase in the postoperative Meary angle (hazard ratio, 1.052; 95% confidence interval, 0.999-1.108; P = .0528) approached significance for the development of tibiotalar tilt., Conclusion: The development of valgus tibiotalar tilt following hindfoot fusion was a notable phenomenon, occurring in 27% of our patient population. The preoperative Meary angle was the only radiographic measurement that was significantly associated with the development of valgus tibiotalar tilt, although the postoperative Meary angle approached significance. These findings should encourage surgeons to be aware of patients with large deformities and of their propensity to develop a valgus deformity about the ankle., Level of Evidence: Level III, retrospective comparative series.

The tibiotalar joint's unique biomechanics and associated structures carry management implications that vary from those in knee or hip arthritis.

Herein we report the synthesis of twelve 2,5-substituted 4-(trifluoromethyl)-spirochromeno[4,3-d]pyrimidines (7-10), as well as an evaluation of their analgesic effect in a mouse pain model. The nine new chromeno[4,3-d]pyrimidines (7-9) were synthesized from the cyclocondensation reactions of three 2,2,2-trifluoro-1-(4-methoxyspiro[chromene-2,1'-cycloalkane]-3-yl)ethanones (3) containing 5-, 6- and 7-membered spirocycloalkanes, with some well-known amidine salts (4-6) [NH 2 CR(NH)]-in which R=Me, Ph, and NH 2 -at yields of 60-95%. Subsequently, three new 2-(pyrrol-1-yl)-4-(trifluoromethyl)-chromeno[4,3-d]pyrimidines (10) were obtained through a Clauson-Kaas reaction between the respective 2-(amino)-4-(trifluoromethyl)-chromeno[4,3-d]pyrimidines (9) and 2,5-dimethoxy-tetrahydrofuran. The analgesic evaluation showed that these 4-(trifluoromethyl)chromeno[4,3-d]pyrimidines (100mg/kg, p.o.) and Ketoprofen (100mg/kg, p.o.) significantly reduced capsaicin-induced spontaneous nociception. Moreover, the 2-pyrrolyl-spirocyclohexane derivative 10b (100 and 300mg/kg, p.o.) had an anti-allodynic effect comparable to Ketoprofen (100 and 300mg/kg, p.o.) in the arthritic pain model, without causing locomotor alterations in the mice. These results suggest that the compound 10b is a promising molecule for new analgesic drugs in the treatment of pathological pain, such as in arthritis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose The purpose of the study was to determine the extent to which arthritis-related limitations are salient in predicting less than the recommended amount of time for adults with prediabetes to spend on moderate or vigorous physical activity. Methods Data from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) in the United States were used to identify the predictors of insufficient physical activity in a large sample of adults with prediabetes 20 years of age and older (n = 2536). Results When extrapolated to more than 45 million adults in the United States at least 20 years of age with prediabetes, 42.7% had insufficient physical activity. Having arthritis-related functional limitations was a significant predictor of insufficient physical activity, even after accounting for the statistically significant contributions of female sex, older age, lower education level, higher body mass index, and depression. Conclusion When educating and counseling adults with prediabetes, diabetes educators should assess for arthritis-related functional limitations when examining factors that may affect prediabetes progression. Recommendations for physical activity for those with mobility and other limitations need to be individualized within a tailored exercise program to accommodate their specific limitations.

Background: In the United States, doctor-diagnosed arthritis is a common and disabling chronic condition. Arthritis can lead to severe joint pain and poor physical function, and it can negatively affect quality of life., Methods: CDC analyzed 2013-2015 data from the National Health Interview Survey, an annual, nationally representative, in-person interview survey of the health status and behaviors of the noninstitutionalized civilian U.S. adult population, to update previous prevalence estimates of arthritis and arthritis-attributable activity limitations., Results: On average, during 2013-2015, 54.4 million (22.7%) adults had doctor-diagnosed arthritis, and 23.7 million (43.5% of those with arthritis) had arthritis-attributable activity limitations (an age-adjusted increase of approximately 20% in the proportion of adults with arthritis reporting activity limitations since 2002 [p-trend <0.001]). Among adults with heart disease, diabetes, and obesity, the prevalences of doctor-diagnosed arthritis were 49.3%, 47.1%, and 30.6%, respectively; the prevalences of arthritis-attributable activity limitations among adults with these conditions and arthritis were 54.5% (heart disease), 54.0% (diabetes), and 49.0% (obesity)., Conclusions and Comments: The prevalence of arthritis is high, particularly among adults with comorbid conditions, such as heart disease, diabetes, and obesity. Furthermore, the prevalence of arthritis-attributable activity limitations is high and increasing over time. Approximately half of adults with arthritis and heart disease, arthritis and diabetes, or arthritis and obesity are limited by their arthritis. Greater use of evidence-based physical activity and self-management education interventions can reduce pain and improve function and quality of life for adults with arthritis and also for adults with other chronic conditions who might be limited by their arthritis.

Objectives: Previous studies have shown a tendency for reduced motor cortex inhibition in chronic pain populations. People with chronic pain also routinely demonstrate motor deficiencies, including skill learning. The goals of the current study were to (1) provide a thorough analysis of corticomotor and intracortical excitability in people with chronic arthritic hand pain, and (2) examine the relationship between these measures and performance on a motor skill learning task., Methods: Twenty-three people with arthritic hand pain and 20 pain-free controls participated in a cross-sectional study. Transcranial magnetic stimulation was used to assess corticomotor and intracortical excitability of the first dorsal interosseus muscle. Participants then completed a 30-minute motor skill training task involving the index finger of the same hand., Results: Hand arthritis participants showed evidence of reduced intracortical inhibition and enhanced facilitation, which correlated with duration of hand pain. Arthritis participants were initially poorer at the motor skill task but over the total training time performance was equivalent between groups. There were no associations found between measures of intracortical excitability and motor skill learning., Discussion: Our findings are the first to provide evidence of cortical disinhibition in people with painful arthritis, as previously demonstrated in other chronic pain populations. Cortical excitability changes may progress the longer pain persists, with increased pain duration being associated with greater cortical disinhibition. There was no evidence that these changes in cortical excitability are related to impaired motor function or skill learning.