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ID PMID Title PublicationDate abstract
29292085 Investigation of autoantibodies to SP-1 in Chinese patients with primary Sjögren's syndro 2018 Mar In order to evaluate autoantibody to SP-1 as an early biomarker in pSS, we investigated autoantibody to SP-1 in Chinese patients with primary Sjögren's syndrome (pSS). Autoantibodies to SP-1 are significantly increased in pSS patients compared to RA patients, SLE patients, and healthy people without secondary SS. The presence of anti SP-1 antibodies was negatively correlated with the focus score (FS), RF, and salivary gland function. It was positively correlated with FS=0, RF≤20, and normal salivary gland function. In further studies, the autoantigen SP-1 was identified in ductal epithelia of salivary glands in il14α TG mice by IIF. SP-1 mRNAs expression increased with growing age in il14α TG mice. SP-1 mRNA was also identified in labial biopsies of patients with pSS. In conclusion, autoantibody to SP-1 is an early marker in pSS. It is useful to diagnose pSS patients who lack RF or antibodies to Ro/La.
30279267 Tocilizumab in patients with adult-onset still's disease refractory to glucocorticoid trea 2018 Dec OBJECTIVE: To evaluate the efficacy and safety of tocilizumab, an interleukin-6 receptor antibody, in patients with adult-onset Still's disease. METHODS: In this double-blind, randomised, placebo-controlled phase III trial, 27 patients with adult-onset Still's disease refractory to glucocorticoids were randomised to tocilizumab at a dose of 8 mg/kg or placebo given intravenously every 2 weeks during the 12-week, double-blind phase. Patients received open-label tocilizumab for 40 weeks subsequently. The primary outcome was American College of Rheumatology (ACR) 50 response at week 4. The secondary outcomes included ACR 20/50/70, systemic feature score, glucocorticoid dose and adverse events at each point. RESULTS: In the full analysis set, ACR50 response at week 4 was achieved in 61.5% (95% CI 31.6 to 86.1) in the tocilizumab group and 30.8% (95% CI 9.1 to 61.4) in the placebo group (p=0.24). The least squares means for change in systemic feature score at week 12 were -4.1 in the tocilizumab group and -2.3 in the placebo group (p=0.003). The dose of glucocorticoids at week 12 decreased by 46.2% in the tocilizumab group and 21.0% in the placebo group (p=0.017). At week 52, the rates of ACR20, ACR50 and ACR70 were 84.6%, 84.6% and 61.5%, respectively, in both groups. Serious adverse events in all participants who received one dose of tocilizumab were infections, aseptic necrosis in the hips, exacerbation of adult-onset Still's disease, drug eruption and anaphylactic shock. CONCLUSION: The study suggests that tocilizumab is effective in adult-onset Still's disease, although the primary endpoint was not met and solid conclusion was not drawn.
30299247 Prevalence of sicca syndrome in the Peruvian population. 2019 May OBJECTIVES: Sjögren's syndrome is a complex and heterogeneous autoimmune disease characterised by ocular and oral dryness (1), which mainly affects the exocrine glands. The objective of this study was to determine the prevalence of sicca syndrome (SS) in the Peruvian population. The age and gender of patients with SS and their national prevalence and in each of the departments were defined. METHODS: This was a cross-sectional prevalence study. All the people for whom the Ministry of Health (MINSA) in Peru covered health treatments from January to December 2016 were taken into account. The patients with SS were either newly or previously diagnosed with sicca syndrome (Sjögren's) according to the international classification of diseases version 10 (ICD-10) of the World Health Organization (WHO). The prevalence was determined considering the number of cases of SS in the total population registered by the Ministry of Health (MINSA). RESULTS: 1,301 cases of SS were observed in a total population of 15,417,345 people served in 25 territories. The prevalence of SS in this population was 0.0084%, the prevalence rate was 8.4 cases per 100,000 persons (95% CI: 7.99-8.91). The prevalence of SS was higher in the territories of Tacna, Lima, La Libertad, Arequipa, Callao, and Apurímac. CONCLUSIONS: The results of this study show the prevalence of SS in the Peruvian population and serve to strengthen the health strategies of rheumatology, ophthalmology, and oral health to improve the diagnosis, treatment, follow-up of the disease, and the quality of life of patients with SS.
29320472 Subjective Complaints of Ocular Dryness and Xerostomia Among the Non-Sjögren Adult Popula 2018 Jan 10 BACKGROUND Eye and mouth dryness are the most common symptoms reported during ophthalmological and dental examinations, and their frequency increases with age. In connection with population aging and the huge variety of factors and conditions that can induce this condition, it is becoming a serious and growing problem. The purpose of the present study was to determine whether ocular dryness and concomitant xerostomia is associated with particular systemic diseases. MATERIAL AND METHODS We enrolled 642 non-Sjögren patients referred for examination to the ophthalmology or dental clinic of Lublin region, Poland. The research was conducted using a standardized interview: The Interview and Examination Questionnaire. All patients responded to the survey questions, which concerned systemic diseases, lifestyle, with special emphasis on computer work, spending time in polluted and air-conditioned rooms, and subsequent questions about the subjective symptoms of ocular and mouth dryness. RESULTS There were 424 patients who presented signs and symptoms of both ocular and mouth dryness. Our study showed a statistically significant association between this condition and the age and sex of the patients and systemic diseases such as hypertension (p=0.0000), cardiovascular disease (p=0.057), and stress (p=0.036), and time spent at the computer (p=0.00015). CONCLUSIONS Ocular dryness and concomitant xerostomia may occur in apparently healthy individuals, but is more frequent in patients with systemic disorders. The lack of dry eye and dry mouth symptoms does not exclude insufficient tearing and salivation; thus, the disorders are usually underestimated. Our study indicates that ocular and mouth dryness are the most common conditions seen in out-patients, due to increased use of medications, computers, and air conditioning.
29468503 Abnormal lipid metabolism in a rat model of arthritis: one possible pathway. 2018 Nov Collagen-induced arthritis (CIA) animal model is associated with systemic manifestations, including alteration of lipid metabolism. In the present study, one possible pathway of altered lipid metabolism is proposed. Specimens of joint tissue and plasma were collected from the CIA and control rats, and quantitative analysis of lipid components was performed by nuclear magnetic resonance (NMR) spectroscopy technique. Correlation analysis was performed between the level of lipid components and antioxidant enzymes, lactate dehydrogenase (LDH), lipid peroxidation (LP), and cytokines in joint tissue and plasma. Differentiation between the CIA and control rats was established on the basis of the quantity of lipid components in the joint tissue and plasma. Positive correlation was observed for all the enzymes vs. lipid components as well as LP vs. lipid components in plasma and joint tissue. Positive correlation was observed for enzymes in plasma and joint tissue. A negative correlation was observed in between the plasma and joint tissue with the level of lipid components. Cytokine levels were also correlated with the level of lipid components and ratios of saturated fatty acids/unsaturated fatty acids in plasma and joint tissue. Inflammatory disease activity in CIA rats with synovitis brought about a significant change in lipid metabolism. Taken together, the results of our study are delineating a possible pathway of altered lipid metabolism in the CIA rat model, thereby contributing further to an understanding of the pathophysiology of rheumatoid arthritis (RA).
29576791 A Systematic Review about the Efficacy and Safety of Tripterygium wilfordii Hook.f. Prepar 2018 Tripterygium wilfordii Hook.f. (TWHF) is a traditional Chinese herb long used for rheumatoid arthritis (RA) treatment, in modern times, often in the form of various Tripterygium wilfordii Hook.f. preparations (TWPs). This systematic review and meta-analysis focuses on analyzing the clinical efficacy and safety of TWPs in the treatment of RA. Databases were searched to collect the randomized controlled trials (RCTs) on TWPs treating RA published on or before April 10, 2017. Data from 11 studies were included in this meta-analysis. Compared with the control group, TWPs can increase effectiveness, while decreasing erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), and risk of adverse events. TWPs treatment was also more effective than treatment by conventional western medicine (CWM) and Chinese patent medicine or placebo (COP). TWPs significantly decreased the risk of adverse events compared with the CWM group, but not compared with the COP group. Current evidence shows that TWPs are more effective than other western or Chinese medicines we included in this meta-analysis for RA treatment with relatively lower toxicity.
30632540 Turkish League Against Rheumatism (TLAR) Recommendations for the Pharmacological Managemen 2018 Sep OBJECTIVES: This study aims to report the assessment of the Turkish League Against Rheumatism (TLAR) expert panel on the compliance and adaptation of the European League Against Rheumatism (EULAR) 2016 recommendations for the management of rheumatoid arthritis (RA) in Turkey. PATIENTS AND METHODS: The EULAR 2016 recommendations for the treatment of RA were voted by 27 specialists experienced in this field with regard to participation rate for each recommendation and significance of items. Afterwards, each recommendation was brought forward for discussion and any alteration gaining ≥70% approval was accepted. Also, Turkish version of each item was rearranged. Last version of the recommendations was then revoted to determine the level of agreement. Levels of agreement of the two voting rounds were compared with Wilcoxon signed-rank test. In case of significant difference, the item with higher level of agreement was accepted. In case of no difference, the changed item was selected. RESULTS: Four overarching principles and 12 recommendations were assessed among which three overarching principles and one recommendation were changed. The changed overarching principles emphasized the importance of physical medicine and rehabilitation specialists as well as rheumatologists for the care of RA patients in Turkey. An alteration was made in the eighth recommendation on treatment of active RA patients with unfavorable prognostic indicators after failure of three conventional disease modifying anti-rheumatic drugs. Remaining principles were accepted as the same although some alterations were suggested but could not find adequate support to reach significance. CONCLUSION: Expert opinion of the TLAR for the treatment of RA was composed for practices in Turkish rheumatology and/or physical medicine and rehabilitation clinics.
29565986 An unfavorable body composition is common in early arthritis patients: A case control stud 2018 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.
30886973 In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494). 2018 BACKGROUND: Anti-cytokine therapies such as adalimumab, tocilizumab, and the small molecule JAK inhibitor tofacitinib have proven that cytokines and their subsequent downstream signaling processes are important in the pathogenesis of rheumatoid arthritis. Tofacitinib, a pan-JAK inhibitor, is the first approved JAK inhibitor for the treatment of RA and has been shown to be effective in managing disease. However, in phase 2 dose-ranging studies tofacitinib was associated with dose-limiting tolerability and safety issues such as anemia. Upadacitinib (ABT-494) is a selective JAK1 inhibitor that was engineered to address the hypothesis that greater JAK1 selectivity over other JAK family members will translate into a more favorable benefit:risk profile. Upadacitinib selectively targets JAK1 dependent disease drivers such as IL-6 and IFNγ, while reducing effects on reticulocytes and natural killer (NK) cells, which potentially contributed to the tolerability issues of tofacitinib. METHODS: Structure-based hypotheses were used to design the JAK1 selective inhibitor upadacitinib. JAK family selectivity was defined with in vitro assays including biochemical assessments, engineered cell lines, and cytokine stimulation. In vivo selectivity was defined by the efficacy of upadacitinib and tofacitinib in a rat adjuvant induced arthritis model, activity on reticulocyte deployment, and effect on circulating NK cells. The translation of the preclinical JAK1 selectivity was assessed in healthy volunteers using ex vivo stimulation with JAK-dependent cytokines. RESULTS: Here, we show the structural basis for the JAK1 selectivity of upadacitinib, along with the in vitro JAK family selectivity profile and subsequent in vivo physiological consequences. Upadacitinib is ~ 60 fold selective for JAK1 over JAK2, and > 100 fold selective over JAK3 in cellular assays. While both upadacitinib and tofacitinib demonstrated efficacy in a rat model of arthritis, the increased selectivity of upadacitinib for JAK1 resulted in a reduced effect on reticulocyte deployment and NK cell depletion relative to efficacy. Ex vivo pharmacodynamic data obtained from Phase I healthy volunteers confirmed the JAK1 selectivity of upadactinib in a clinical setting. CONCLUSIONS: The data presented here highlight the JAK1 selectivity of upadacinitinib and supports its use as an effective therapy for the treatment of RA with the potential for an improved benefit:risk profile.
29125905 Arthritis After Cancer Immunotherapy: Symptom Duration and Treatment Response. 2019 Mar OBJECTIVE: Musculoskeletal manifestations of immune-related adverse events (irAEs) after checkpoint inhibitor immunotherapy for cancer remain incompletely characterized and poorly understood. A recently published case series suggested that immunotherapy-induced arthritis is an aggressive process requiring high-dose corticosteroids. METHODS: This was a retrospective chart review of all patients with musculoskeletal irAEs first seen by one of the authors between 2014 and 2016. All patients had been treated for a malignancy with immune checkpoint inhibitors targeting PD-1 (nivolumab, pembrolizumab), PD-L1 (durvalumab), and/or CTLA-4 (ipilimumab, tremelimumab) at Memorial Sloan Kettering Cancer Center. RESULTS: We identified 10 patients with a mean ± SD age of 63.2 ± 9.7 years. Seven were treated with a combination of checkpoint inhibitors and 3 with nivolumab monotherapy. Four patients developed inflammatory polyarthritis, 4 oligoarthritis, and 2 tenosynovitis. Six were antinuclear antibody positive and 2 had anti-cyclic citrullinated peptide antibodies. Mean ± SD time from the first dose of immunotherapy until joint involvement was 6.3 ± 4.3 months. All 10 patients were treated with systemic corticosteroids, but 6 of 10 required ≤20 mg per day of prednisone. Five patients received steroid-sparing agents. Mean ± SD time until resolution of joint symptoms after the last dose of immunotherapy was 9.2 ± 6.1 months. CONCLUSION: Musculoskeletal irAEs can manifest as a rheumatoid arthritis-like polyarthritis, oligoarthritis, tenosynovitis, or polymyalgia rheumatica. Musculoskeletal symptoms can last more than a year, but they can generally be managed with low to moderate doses of corticosteroids.
29657223 Distal renal tubular acidosis in Sjögren's syndrome. 2018 Mar Interstitial nephritis and immune complex-mediated glomerulonephritis are the two common renal manifestations of primary Sjögren's syndrome (SS). Here, we discuss three cases of primary SS where presenting manifestation was distal renal tubular acidosis. The possibility of an underlying autoimmune disorder should be considered in a patient presenting with distal tubular acidosis or recurrent hypokalemic periodic paralysis as treatment of primary disease improves the outcome of illness.
30411528 Clinical features and potential relevant factors of renal involvement in primary Sjögren' 2019 Feb OBJECTIVE: To investigate distinct features of renal involvement in patients with primary Sjögren's syndrome (pSS) and to identify potential factors associated with renal involvement. METHODS: Four hundred and thrity-four pSS patients from the Rheumatology Department of the First Affiliated Hospital of Wenzhou Medical University from 2013 to 2017 were included in a cross-sectional study. Patients with renal involvement were compared with their age- and gender-matched controls (pSS without renal involvement). Demographic, clinical, histological, nephritic, immunological features of renal involvement in pSS were systematically analyzed. Possible factors related to renal involvement were identified using multivariate logistic regression analyses. RESULTS: One hundred and ninety-two pSS patients (88.48%) with renal involvement were women with mean age of nearly 58 years and mean disease duration of above 4 years. Clinical manifestation, serologic and immunological features and renal biopsy class of the pSS patients with renal involvement were presented. By multivariate analyses, xerophthalmia, histological positivity for lower salivary gland biopsy (LSGB), anti-SSA/Ro52-positive, reduced complement 3 (C3) levels, hypoalbuminemia and anemia retained significant association with renal involvement in pSS (all P < 0.05). CONCLUSION: In addition to LSGB pattern, anti-SSA/Ro52-positivity, reduced C3 levels, hypoalbuminemia and anemia, also indicate significant association with renal involvement in pSS. Therefore, early vigilance is required for patients with these clinical manifestations.
30006919 Prevalence of overlap of antineutrophil cytoplasmic antibody associated vasculitis with sy 2019 Jan We aimed to estimate the frequency of overlap of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with systemic autoimmune diseases. Retrospective single-center study to identify patients with AAV diagnosis and concomitant autoimmune systemic diseases, simultaneously, before or after the diagnosis of AAV. Sociodemographic characteristics, such as comorbidities; follow-up time; type of AAV; disease duration; relapses; treatment and response; clinical, serological, and histological characteristics; disease activity and damage; prognosis; dialysis requirements, and death were assessed. Twenty-eight of two hundred and forty-seven patients (11.3%) with AAV had a concomitant diagnosis of autoimmune disease. The predominant AAV type was renal-limited vasculitis (39%), followed by granulomatosis with polyangiitis (29%), mycroscopic polyangiitis (25%), and eosinophilic granulomatosis with polyangiitis (7%). Mean age at AAV diagnosis was 50 ± 17 years and 24/28 were ANCA positive. The main clinical manifestations were renal (79%), otorhinolaryngologic (43%), and pulmonary and peripheral neuropathy (32%). Sixteen patients (57%) experienced partial or total remission at a median follow-up of 34 months, and four patients (14%) died. The most frequent autoimmune disease overlapped was rheumatoid arthritis (39%), followed by Sjögren's syndrome and systemic sclerosis (14%), mixed connective tissue disease (11%), systemic lupus erythematosus and juvenile idiopathic arthritis (7%), and ankylosing spondylitis and IgG4-related disease (4%). In nine patients (32%), both diagnoses were simultaneous; in the rest, median time elapsed between the autoimmune disease and AAV diagnosis was 173 months. The prevalence of overlap AAV with other autoimmune diseases was low. The most common AAV phenotype was renal-limited vasculitis, and the most frequent overlap disease was rheumatoid arthritis.
29619205 Deformylation reaction-based probe for in vivo imaging of HOCl. 2018 Jan 14 The detection of hypochlorous acid (HOCl) in vivo is vitally important because the local concentration of HOCl is highly correlated with some diseases such as atherosclerosis and rheumatoid arthritis. However, in vivo detection of HOCl remains a challenge due to the lack of a suitable probe. We report here a near-infrared (NIR) emissive "turn-on" probe (FDOCl-1) based on a methylene blue derivative, which can quickly detect HOCl via a newly found deformylation mechanism. FDOCl-1 displays remarkable selectivity and sensitivity towards HOCl. The dramatic changes in colour and NIR emission were used to detect HOCl in vitro and in vivo in a mouse arthritis model.
28544822 Cost-Effectiveness of Tight Control of Inflammation in Early Psoriatic Arthritis: Economic 2018 Mar OBJECTIVE: Treat-to-target approaches have proved to be effective in rheumatoid arthritis, but have not been studied in psoriatic arthritis (PsA). This study was undertaken to examine the cost-effectiveness of tight control (TC) of inflammation in early PsA compared to standard care. METHODS: Cost-effectiveness analyses were undertaken alongside a UK-based, open-label, multicenter, randomized controlled trial. Taking the perspective of the health care sector, effectiveness was measured using the 3-level EuroQol 5-domain, which allows for the calculation of quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratios (ICERs) are presented, which represent the additional cost per QALY gained over a 48-week time horizon. Sensitivity analyses are presented assessing the impact of variations in the analytical approach and assumptions on the cost-effectiveness estimates. RESULTS: The mean cost and QALYs were higher in the TC group: £4,198 versus £2,000 and 0.602 versus 0.561. These values yielded an ICER of £53,948 per QALY. Bootstrapped uncertainty analysis suggests that the TC has a 0.07 probability of being cost-effective at a £20,000 threshold. Stratified analysis suggests that with certain costs being controlled, an ICER of £24,639 can be calculated for patients with a higher degree of disease severity. CONCLUSION: A tight control strategy to treat PsA is an effective intervention in the treatment pathway; however, this study does not find tight control to be cost-effective in most analyses. Lower drug prices, targeting polyarthritis patients, or reducing the frequency of rheumatology visits may improve value for money metrics in future studies.
29973288 Bilateral septic arthritis of the sternoclavicular joint complicating infective endocardit 2018 Jul 5 BACKGROUND: Septic arthritis is an infectious disease that commonly affects weight-bearing or proximal joints such as the knee and the hip. The sternoclavicular joint is an unusual site of this entity. It usually occurs in patients with diabetes mellitus, intravenous drug abusers, or those with rheumatoid arthritis. Analysis of the previous literature showed few articles and these described essentially cases of unilateral presentation. CASE PRESENTATION: We report a rare case of a bilateral septic arthritis of the sternoclavicular joint sustained by a 71-year-old Tunisian woman whose medical history was significant for methicillin-resistant Staphylococcus aureus infective endocarditis 6 months ago. Imaging investigations revealed destruction of the medial extremities of her two clavicles and bilateral collections in the soft tissues around her sternoclavicular joints. She was treated successfully by needle aspiration drainage combined with a 12-week antibiotherapy. CONCLUSIONS: Bilateral septic arthritis of the sternoclavicular joint is an extremely rare entity, with a paucity of literature. Only early diagnosis, which is obtained from the culture of the joint fluid using needle aspiration, allows satisfactory functional outcome and a good prognosis. Osteoarticular infections should be considered in patients with recent infective endocarditis in cases of fever recurrence.
31657698 Polyarthritis and its differential diagnosis. 2019 Oct Polyarthritis is a term used when at least five joints are affected with arthritis. Several different diseases ranging from rheumatoid arthritis to infection diseases can lead to polyarthritis. Anamnesis, physical examination, laboratory findings and imaging methods are important tools to differential diagnosis.
31657699 Are there any differences among psoriasis, psoriatic arthritis and rheumatoid arthritis in 2019 Oct OBJECTIVE: Although the frequency of metabolic syndrome has been studied separately in psoriasis, psoriatic arthritis (PsA), and rheumatoid arthritis (RA) patients, there is no study that compares the prevalence of metabolic syndrome in all three diseases. The purpose of this study is to evaluate the relationship between metabolic syndrome (MetS) and chronic low-grade inflammatory diseases, and to determine the frequency of MetS and insulin resistance in psoriasis and PsA as compared to RA. METHODS: A total of 155 patients were included in this cross-sectional study. Fifty patients who were diagnosed with psoriasis, 55 PsA patients who were diagnosed according to the CASPAR criteria, and 50 seropositive RA patients who were diagnosed according to the ACR/EULAR 2010 classification criteria were included in this study. MetS was diagnosed by the 2005 criteria of International Diabetes Federation. The cardiovascular risk factors and parameters associated with MetS were evaluated. RESULTS: The patients' mean age was significantly higher in the RA. MetS was determined in 33.5% of all patients and MetS and insulin resistance showed no significant difference among the three groups (psoriasis: 36%, PsA: 29%, RA: 36%; p: 0.684 and psoriasis: 70%, PsA: 64%, RA: 66%, respectively; p: 0.785). Triglyceride levels were higher in psoriasis and PsA as compared to the RA (psoriasis: 34%, PsA: 32.7%, RA: 16%, respectively; p: 0.045). The frequency of hypertension was 38% in the RA, which was higher than PsA and psoriasis (p: 0.011). CONCLUSION: In all three groups, the prevalence of MetS was shown to be higher than the general population. The lack of difference between these groups may be due to the small number of patients, the retrospective study design, and the inequality of the population with respect to age and gender.
29743640 Trivalent soluble TNF Receptor, a potent TNF-α antagonist for the treatment collagen-indu 2018 May 9 Tumor necrosis factor is a major pro-inflammatory cytokine which triggers various physiological consequences by binding to and trimerizing its receptors, and has been the single most sought-after drug target for intervening autoimmune diseases such as rheumatoid arthritis and psoriasis. However, current TNF-α blockers, including soluble receptor-Fc fusion and therapeutic antibodies, are all dimeric in structure, whereas their target TNF-α itself is homotrimeric in nature. Here we describe the development of a trivalent soluble TNF receptor and show that it is a more potent than the dimeric TNF receptor decoys in inhibiting TNF-α signaling both in vitro and in vivo. The process involves gene fusion between a soluble receptor TNFRII with a ligand binding domain and a trimerization tag from the C-propeptide of human collagen (Trimer-Tag), which is capable of self-assembly into a covalently linked trimer. We show that the homotrimeric soluble TNF receptor (TNFRII-Trimer) produced with such method is more potent in ligand binding kinetics and cell based bioassays, as well as more efficacious in attenuating collagen-induced arthritis (CIA) in a mouse model than its dimeric TNFRII-Fc counterpart. Thus, this work demonstrates the proof of concept of Trimer-Tag and provides a new platform for rational designs of next generation biologic drugs.
29947274 Re-arthrodesis after primary ankle fusion: 134/1,716 cases from the Swedish Ankle Registry 2018 Oct Background and purpose - Arthrodesis is the most common treatment of severe ankle arthritis. Large studies on the occurrence of re-arthrodesis are few, especially with information in terms of risk. We used the National Swedish Ankle Registry to assess incidence and risk factors for re-arthrodesis. Patients and methods - In the Registry, we examined the occurrence of re-arthrodesis in 1,716 patients with a primary ankle arthrodesis. We also analyzed associations between the re-arthrodesis risk and sex, diagnosis, and surgical method. Results - The risk of first re-arthrodesis at 2.5 years was 7.4% and the rate at 9 years 7.8%. The risk following arthroscopic surgery with fixation by screws was 15%, which is statistically significantly higher than the 8% following the gold standard technique with open screw fixation, the 5% following fixation by intramedullary nailing, and the 3% following fixation by plate and screws. Patients with either idiopathic osteoarthritis or posttraumatic arthritis had a higher risk of re-arthrodesis than patients with rheumatoid arthritis. We could not find that the risk of re-arthrodesis was associated with sex. Interpretation - In Sweden, the re-arthrodesis risk varied by primary technique and was especially high after arthroscopic surgery. Reasons are unknown but poor surgical technique and/or surgeon inexperience may contribute, as may patient selection.