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ID PMID Title PublicationDate abstract
27196876 Burden of Visual Impairment and Chronic Diseases. 2016 Jul 1 IMPORTANCE: Visual impairment (VI) is an emerging public health concern, especially considering the aging population. However, unlike other major chronic diseases, VI is often overlooked by investigators assessing the burden of diseases. OBJECTIVES: To provide a description of preference weights for VI and chronic diseases from a national survey and estimate the corresponding burden of these diseases. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was conducted using a multistage, probability-cluster survey, which can produce nationally representative estimates. Data on 29 639 participants 19 years or older from the 2008-2012 Korean National Health and Nutrition Examination Survey were analyzed in terms of vision assessment, status of chronic diseases, and the European Quality of Life-Five Dimensions Questionnaire (EQ-5D). Visual impairment was defined as the presenting distance best-corrected visual acuity of worse than decimal 0.5. Data analysis was conducted from August 14, 2008, and September 7, 2015. MAIN OUTCOMES AND MEASURES: Preference weights (utilities) and prevalence-based quality-adjusted life-year (QALY) losses. RESULTS: Of the 29 639 participants, 28 382 with VA or EQ-5D measurements were included in the analysis; they had a mean (SE) age of 45.05 (0.19) years and a mean EQ-5D index of 0.948 (0.001). The preference weight for VI was -0.0549 (95% CI, -0.0777 to -0.0321), which was the third highest value among the 12 diseases analyzed-preceded only by the preference weights for osteoarthritis or rheumatoid arthritis (-0.0688; 95% CI, -0.748 to -0.0628) and stroke (-0.0666; 95% CI, -0.0854 to -0.0479). The estimated annual QALY loss from VI was -74.93 years per 100 000 person-years; this loss is comparable to or higher than that associated with other major chronic conditions (eg, diabetes mellitus, dyslipidemia, stroke, myocardial infarction/ischemic heart disease, asthma, obesity, and anemia). Visual impairment accounted for 4.77% of the total estimated QALY loss in the Korean population aged 19 years or older. CONCLUSIONS AND RELEVANCE: The present study provides a description of preference weights for VI and various chronic diseases from a national survey. Furthermore, it reveals the distributions of public burden from these conditions, and compared them in this regard. Although details might vary across the populations having different cultural and socioeconomic backgrounds, the results underscore the importance of VI for quality of life and as a public health burden compared with other major chronic diseases.
27144583 Regulatory T Cells Contribute to the Inhibition of Radiation-Induced Acute Lung Inflammati 2016 Apr 30 Bee venom has long been used to treat various inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis. Previously, we reported that bee venom phospholipase Aâ‚‚ (bvPLAâ‚‚) has an anti-inflammatory effect through the induction of regulatory T cells. Radiotherapy is a common anti-cancer method, but often causes adverse effects, such as inflammation. This study was conducted to evaluate the protective effects of bvPLAâ‚‚ in radiation-induced acute lung inflammation. Mice were focally irradiated with 75 Gy of X-rays in the lung and administered bvPLAâ‚‚ six times after radiation. To evaluate the level of inflammation, the number of immune cells, mRNA level of inflammatory cytokine, and histological changes in the lung were measured. BvPLAâ‚‚ treatment reduced the accumulation of immune cells, such as macrophages, neutrophils, lymphocytes, and eosinophils. In addition, bvPLAâ‚‚ treatment decreased inflammasome-, chemokine-, cytokine- and fibrosis-related genes' mRNA expression. The histological results also demonstrated the attenuating effect of bvPLAâ‚‚ on radiation-induced lung inflammation. Furthermore, regulatory T cell depletion abolished the therapeutic effects of bvPLAâ‚‚ in radiation-induced pneumonitis, implicating the anti-inflammatory effects of bvPLAâ‚‚ are dependent upon regulatory T cells. These results support the therapeutic potential of bvPLAâ‚‚ in radiation pneumonitis and fibrosis treatments.
27109480 Anti-inflammatory activity of chloroquine and amodiaquine through p21-mediated suppression 2016 May 27 Chloroquine (CQ) and amodiaquine (AQ) have been used for treating or preventing malaria for decades, and their application has expanded into treating inflammatory disease in humans. CQ and AQ are applicable for controlling rheumatoid arthritis, but their molecular mechanisms of anti-inflammatory activity remain to be elucidated. In this study, we examined the effects of CQ and AQ on T cell activation and T cell-mediated immune response. CQ had no significant effect on T cell numbers, but decreased the population of T cells with a high division rate. However, AQ treatment significantly increased the number of cells with low division rates and eliminated cells with high division rates, resulting in the inhibition of T cell proliferation triggered by T cell receptor stimulation, of which inhibition occurred in developing effector T helper and regulatory T cells, regardless of the different exogenous cytokines. Interestingly, the cyclin-dependent kinase inhibitor p21 was significantly and dose-dependently increased by CQ, and more potently by AQ, while other cell cycle regulators were unchanged. Both CQ and AQ elevated the transcription level of p21 though the activation of p53, but also blocked p21 protein degradation in the presence of cycloheximide, causing p21 protein accumulation mainly in the nucleus. Sustained treatment of developing T cells with either CQ or AQ suppressed IFN-γ production in a dose dependent manner and potently inhibited the differentiation of IFN-γ-producing Th1 cells. These results demonstrate that CQ and AQ increase the expression level of p21 and inhibit T cell proliferation and the development of IFN-γ-producing Th1 cells, thereby revealing beneficial roles in treating a wide range of chronic inflammatory diseases mediated by inflammatory T cells.
27001307 Intercellular Communication between Keratinocytes and Fibroblasts Induces Local Osteoclast 2016 Jun 1 Bone homeostasis is maintained by a balance in activity between bone-resorbing osteoclasts and bone-forming osteoblasts. Shifting the balance toward bone resorption causes osteolytic bone diseases such as rheumatoid arthritis and periodontitis. Osteoclast differentiation is regulated by receptor activator of nuclear factor κB ligand (RANKL), which, under some pathological conditions, is produced by T and B lymphocytes and synoviocytes. However, the mechanism underlying bone destruction in other diseases is little understood. Bone destruction caused by cholesteatoma, an epidermal cyst in the middle ear resulting from hyperproliferation of keratinizing squamous epithelium, can lead to lethal complications. In this study, we succeeded in generating a model for cholesteatoma, epidermal cyst-like tissue, which has the potential for inducing osteoclastogenesis in mice. Furthermore, an in vitro coculture system composed of keratinocytes, fibroblasts, and osteoclast precursors was used to demonstrate that keratinocytes stimulate osteoclast differentiation through the induction of RANKL in fibroblasts. Thus, this study demonstrates that intercellular communication between keratinocytes and fibroblasts is involved in the differentiation and function of osteoclasts, which may provide the molecular basis of a new therapeutic strategy for cholesteatoma-induced bone destruction.
26892362 Progranulin inhibits expression and release of chemokines CXCL9 and CXCL10 in a TNFR1 depe 2016 Feb 19 Progranulin (PGRN), a pleiotrophic growth factor, is known to play an important role in the maintenance and regulation of the homeostatic dynamics of normal tissue development, proliferation, regeneration, and host-defense. PGRN also has potent anti-inflammatory functionality, and deregulated PGRN is associated with rheumatoid arthritis and inflammatory bowel disease. We have previously reported that PGRN directly binds to TNFR and significantly enhances Treg population and stimulates IL-10 production. To further investigate PGRN's function in the immune system we performed a gene array analysis on CD4+ T cells from wild type B6 mice and PGRN -/- mice. We identified many chemokines and their receptors, among which CXCL9 and CXCL10 were most prominent, that were significantly induced in PGRN null mice. Administration of recombinant PGRN protein strongly inhibited TNF and IFN-γ-induced CXCL9 and CXCL10 expression. In addition, CXCL9 expression is strongly upregulated in PGRN KO mice and its level is correlated with severity of inflammation in a dermatitis model. Further, we have demonstrated that PGRN-mediated inhibition of chemokine expression largely depends on TNFR1. Taken together, this study provides new insights into the mechanisms underlying PGRN mediated regulation of various inflammatory and autoimmune diseases.
26790429 Implementation of the Kids-CAT in clinical settings: a newly developed computer-adaptive t 2016 Mar PURPOSE: To describe the implementation process of a computer-adaptive test (CAT) for measuring health-related quality of life (HRQoL) of children and adolescents in two pediatric clinics in Germany. The study focuses on the feasibility and user experience with the Kids-CAT, particularly the patients' experience with the tool and the pediatricians' experience with the Kids-CAT Report. METHODS: The Kids-CAT was completed by 312 children and adolescents with asthma, diabetes or rheumatoid arthritis. The test was applied during four clinical visits over a 1-year period. A feedback report with the test results was made available to the pediatricians. To assess both feasibility and acceptability, a multimethod research design was used. To assess the patients' experience with the tool, the children and adolescents completed a questionnaire. To assess the clinicians' experience, two focus groups were conducted with eight pediatricians. RESULTS: The children and adolescents indicated that the Kids-CAT was easy to complete. All pediatricians reported that the Kids-CAT was straightforward and easy to understand and integrate into clinical practice; they also expressed that routine implementation of the tool would be desirable and that the report was a valuable source of information, facilitating the assessment of self-reported HRQoL of their patients. CONCLUSIONS: The Kids-CAT was considered an efficient and valuable tool for assessing HRQoL in children and adolescents. The Kids-CAT Report promises to be a useful adjunct to standard clinical care with the potential to improve patient-physician communication, enabling pediatricians to evaluate and monitor their young patients' self-reported HRQoL.
26785714 What Strategies Do Physicians and Patients Discuss to Reduce Out-of-Pocket Costs? Analysis 2016 Oct BACKGROUND: More than 1 in 4 Americans report difficulty paying medical bills. Cost-reducing strategies discussed during outpatient physician visits remain poorly characterized. OBJECTIVE: We sought to determine how often patients and physicians discuss health care costs during outpatient visits and what strategies, if any, they discussed to lower patient out-of-pocket costs. DESIGN: Retrospective analysis of dialogue from 1,755 outpatient visits in community-based practices nationwide from 2010 to 2014. The study population included 677 patients with breast cancer, 422 with depression, and 656 with rheumatoid arthritis visiting 56 oncologists, 36 psychiatrists, and 26 rheumatologists, respectively. RESULTS: Thirty percent of visits contained cost conversations (95% confidence interval [CI], 28 to 32). Forty-four percent of cost conversations involved discussion of cost-saving strategies (95% CI, 40 to 48; median duration, 68 s). We identified 4 strategies to lower costs without changing the care plan. They were, in order of overall frequency: 1) changing logistics of care, 2) facilitating co-pay assistance, 3) providing free samples, and 4) changing/adding insurance plans. We also identified 4 strategies to reduce costs by changing the care plan: 1) switching to lower-cost alternative therapy/diagnostic, 2) switching from brand name to generic, 3) changing dosage/frequency, and 4) stopping/withholding interventions. Strategies were relatively consistent across health conditions, except for switching to a lower-cost alternative (more common in breast oncology) and providing free samples (more common in depression). LIMITATION: Focus on 3 conditions with potentially high out-of-pocket costs. CONCLUSIONS: Despite price opacity, physicians and patients discuss a variety of out-of-pocket cost reduction strategies during clinic visits. Almost half of cost discussions mention 1 or more cost-saving strategies, with more frequent mention of those not requiring care-plan changes.
26705675 Mitochondrial DNA haplogroups modify the risk of osteoarthritis by altering mitochondrial 2016 Apr Haplogroup G predisposes one to an increased risk of osteoarthritis (OA) occurrence, while haplogroup B4 is a protective factor against OA onset. However, the underlying mechanism is not known. Here, by using trans-mitochondrial technology, we demonstrate that the activity levels of mitochondrial respiratory chain complex I and III are higher in G cybrids than in haplogroup B4. Increased mitochondrial oxidative phosphorylation (OXPHOS) promotes mitochondrial-related ATP generation in G cybrids, thereby shifting the ATP generation from glycolysis to OXPHOS. Furthermore, we found that lower glycolysis in G cybrids decreased cell viability under hypoxia (1% O2) compared with B4 cybrids. In contrast, G cybrids have a lower NAD(+)/NADH ratio and less generation of reactive oxygen species (ROS) under both hypoxic (1% O2) and normoxic (20% O2) conditions than B4 cybrids, indicating that mitochondrial-mediated signaling pathways (retrograde signaling) differ between these cybrids. Gene expression profiling of G and B4 cybrids using next-generation sequencing technology showed that 404 of 575 differentially expressed genes (DEGs) between G and B4 cybrids are enriched in 17 pathways, of which 11 pathways participate in OA. Quantitative reverse transcription PCR (qRT-PCR) analyses confirmed that G cybrids had lower glycolysis activity than B4 cybrids. In addition, we confirmed that the rheumatoid arthritis pathway was over-activated in G cybrids, although the remaining 9 pathways were not further tested by qRT-PCR. In conclusion, our findings indicate that mtDNA haplogroup G may increase the risk of OA by shifting the metabolic profile from glycolysis to OXPHOS and by over-activating OA-related signaling pathways.
26476844 Prevalence of Drug Combinations Increasing Bleeding Risk Among Warfarin Users With and Wit 2015 Nov PURPOSE: The aim of this study was to analyse the prevalence and predictors of drug combinations increasing bleeding risk among warfarin users with and without Alzheimer's disease (AD). METHODS: This retrospective observational study utilised data from the Finnish MEDALZ-2005 cohort. The MEDALZ-2005 study included all community-dwelling persons with a clinically verified diagnosis of AD at the end of 2005, and one comparison person without AD for each case. Data on drug use was collected from the Prescription Register. We included persons who were warfarin users during the study period 2006-2009. Drug combinations increasing bleeding risk with warfarin included selective serotonin reuptake inhibitors (SSRIs), non-steroidal anti-inflammatory agents (NSAIDs), other antithrombotic drugs and tramadol. Factors associated with combination use were investigated with logistic regression. RESULTS: During the follow-up, 3385 persons with AD and 4830 persons without AD used warfarin. Drug combinations increasing bleeding risk were more common in warfarin users with AD than without AD [35.9 and 30.5%, respectively (p < 0.0001)]. The most common combination was SSRIs and warfarin, which was more common among persons with AD (23.8%) than among persons without AD (10.9%). NSAIDs and warfarin combination was more common among persons without AD. Combination use was associated with AD, female gender, younger age, diabetes mellitus, rheumatoid arthritis and asthma/chronic obstructive pulmonary disease (COPD). CONCLUSIONS: Use of drug combinations increasing bleeding risk was more common among warfarin users with AD. Special attention should be paid to minimise the duration of concomitant use and to find safer alternatives without increased bleeding risk.
26471424 Chlorogenic acid and luteolin synergistically inhibit the proliferation of interleukin-1β 2015 CONTEXT: Chlorogenic acid (CGA) and luteolin (Lut) are the predominant constituents of Caulis Lonicerae, which is usually used in the treatment for rheumatoid arthritis (RA). OBJECTIVE: In this study, we investigated whether CGA and Lut could synergistically inhibit the proliferation of fibroblast-like synoviocytes (FLSs) in RA synovial tissues. METHODS: Rat FLS cells (RSC-364) induced by interleukin (IL)-1β were treated by CGA, Lut or both of them. The apoptosis rates were detected by flow cytometer. Protein expression of key molecules of NF-κB and JAK/STAT signaling pathways were detected by Western blot. RESULTS AND DISCUSSION: Treatment with CGA and Lut inhibited the proliferation of RSC-364 cells stimulated by IL-1β significantly and induced cell apoptosis notably. The ratio of apoptosis in RSC-364 cells induced with IL-1β accompanied by both CGA and Lut increased approximately 7-fold compared with those incubated with IL-1β alone. The results of immunoblot analysis revealed that the key molecules involved in the NF-κB and JAK/STAT-signaling pathways, including NF-κB p50, p100, IKKα/β, gp103, JAK1 and STAT3, were decreased significantly in RSC-364 cells treated by IL-1β plus CAG and Lut compared with those incubated with IL-1β alone. Additionally, the amounts of phospho-IKKα/β and phospho-STAT3 were also decreased significantly in cells treated with CGA and Lut. Furthermore, the synergistic effect of CGA and Lut was superior to the effect of one of these two ingredients. CONCLUSION: Our finding suggested that the combination of CGA and Lut may be a potential therapeutic treatment for the inflammatory proliferation of synoviocytes in patients with RA.
26457691 Cigarette Smoking and Activities of Daily Living in Ocular Myasthenia Gravis. 2016 Mar BACKGROUND: Myasthenia gravis is an autoimmune disease of the neuromuscular junction, commonly affecting the ocular muscles. Cigarette smoking has been shown to influence many autoimmune diseases, including multiple sclerosis and rheumatoid arthritis, but its effect on myasthenia gravis has not been well studied. We sought to determine whether cigarette smoking influenced disease-related symptoms in ocular myasthenia gravis (OMG). METHODS: We performed a prospective, clinic-based cross-sectional study in a single academic neuro-ophthalmology practice. All patients diagnosed with OMG between November 2006 and April 2014 were included. A prospective telephone survey was administered to determine smoking status and myasthenia gravis-related symptom severity. The main outcome measure was the myasthenia gravis-specific activities of daily living (MG-ADL) score, a well-validated marker of symptoms and quality of life in myasthenia gravis. RESULTS: Forty-four patients were included in the analysis. Comparison of MG-ADL ocular subscores between current smokers (3.4 ± 2.6), former smokers (1.8 ± 2.1), and never smokers (1.1 ± 1.5) revealed a statistically significant relationship (P = 0.031) where current smokers had the highest MG-ADL ocular subscores and never smokers the lowest. Comparison of MG-ADL total scores revealed the same relationship (current 5.6 ± 4.5, former 2.9 ± 3.1, never 1.4 ± 2.5, P = 0.003). There were borderline significant correlations of pack years with MG-ADL ocular subscore (r = 0.27, P = 0.074) and MG-ADL total score (r = 0.30, P = 0.051). CONCLUSIONS: Our findings indicate an association between cigarette smoking and symptom severity in OMG. This association suggests that smoking cessation in OMG patients may lead to improved symptom-related quality of life.
26388830 Cathepsin B is a New Drug Target for Traumatic Brain Injury Therapeutics: Evidence for E64 2015 There is currently no therapeutic drug treatment for traumatic brain injury (TBI) despite decades of experimental clinical trials. This may be because the mechanistic pathways for improving TBI outcomes have yet to be identified and exploited. As such, there remains a need to seek out new molecular targets and their drug candidates to find new treatments for TBI. This review presents supporting evidence for cathepsin B, a cysteine protease, as a potentially important drug target for TBI. Cathepsin B expression is greatly up-regulated in TBI animal models, as well as in trauma patients. Importantly, knockout of the cathepsin B gene in TBI mice results in substantial improvements of TBI-caused deficits in behavior, pathology, and biomarkers, as well as improvements in related injury models. During the process of TBI-induced injury, cathepsin B likely escapes the lysosome, its normal subcellular location, into the cytoplasm or extracellular matrix (ECM) where the unleashed proteolytic power causes destruction via necrotic, apoptotic, autophagic, and activated glia-induced cell death, together with ECM breakdown and inflammation. Significantly, chemical inhibitors of cathepsin B are effective for improving deficits in TBI and related injuries including ischemia, cerebral bleeding, cerebral aneurysm, edema, pain, infection, rheumatoid arthritis, epilepsy, Huntington's disease, multiple sclerosis, and Alzheimer's disease. The inhibitor E64d is unique among cathepsin B inhibitors in being the only compound to have demonstrated oral efficacy in a TBI model and prior safe use in man and as such it is an excellent tool compound for preclinical testing and clinical compound development. These data support the conclusion that drug development of cathepsin B inhibitors for TBI treatment should be accelerated.
26339942 Pregnancy-Related Challenges in Systemic Autoimmune Diseases. 2015 Sep The awareness of pregnancy-related physiologic changes and complications is critical for the appropriate assessment and management of pregnant patients with systemic autoimmune diseases. The overlapping features of physiologic and pathological changes, selected autoantibodies, and the use of potentially teratogenic medications can complicate their management during pregnancy. While pregnancy in lupus patients presents an additional risk to an already complex situation, in patients with no disease activity, the risk of a future pregnancy-related complication is relatively low. Anti-Ro and anti-La antibodies increase the risk of neonatal lupus erythematosus, eg, photosensitive rash and irreversible congenital heart block. Antiphospholipid antibodies increase the risk of pregnancy morbidity, eg, fetal loss and early preeclampsia. Pregnancy usually has a positive effect on rheumatoid arthritis; however, a disease flare is common during the postpartum period. Both the rheumatologist and the obstetrician should partner throughout the pregnancy to manage patients for successful outcomes.
26209624 Au-ACRAMTU-PEt3 Alters Redox Balance To Inhibit T Cell Proliferation and Function. 2015 Sep 1 Although T cells play a critical role in protection from viruses, bacteria, and tumors, they also cause autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. Unwanted T cell responses during organ transplant, graft-versus-host disease, and allergies are also major clinical problems. Although drugs are available to suppress unwanted immune responses, they have limited efficacy with serious side effects. Thus, new therapeutics limiting T cell activation, proliferation, and function can make an immediate clinical impact. To identify new suppressors of lymphocyte activation, proliferation, and function, we examined the immunosuppressive activity of gold(I) analogs of platinum-acridine antitumor agents. We found that the gold complex Au-ACRAMTU-PEt3 is a potent suppressor of murine and human T cell activation. Preincubation with Au-ACRAMTU-PEt3 suppresses the proliferation of CD4(+) and CD8(+) T cells at a similar concentration as pharmaceutical grade cyclosporine A. Au-ACRAMTU-PEt3 pretreatment decreases the production of IFN-γ, TNF-α, IL-2, and IL-17 by human and murine CD4(+) and CD8(+) T cells. When mice were treated with Au-ACRAMTU-PEt3 during viral infection, the expansion of virus-specific CD8(+) T cells was decreased 10-fold and viral load was elevated. Taken together, these results demonstrate that Au-ACRAMTU-PEt3 has potent immunosuppressive activity that could be used to suppress immune responses during transplantation and autoimmunity.
26165503 Autophagy protects chondrocytes from glucocorticoids-induced apoptosis via ROS/Akt/FOXO3 s 2015 Dec OBJECTIVE: Glucocorticoids (GCs) have been widely used in the management of osteoarthritis (OA) and rheumatoid arthritis (RA). Nevertheless, there has been some concern about their ability of increasing reactive oxygen species (ROS) in the cartilage. Forkhead-box class O (FOXO) transcription factors have been proved to have a protective role in chondrocytes through regulation of autophagy and defending oxidative stress. The objective of this study was to investigate the role of FOXO3 in Dex-induce up-regulation of ROS. DESIGN: Healthy cartilages debris from six patients were used for chondrocytes culture. After the treatment of dexamethasone (Dex), the ROS levels, autophagic flux, the expression of FOXO3 in chondrocytes were measured. RNA interference technique was also used to determine the role of FOXO3 in Dex-induced autophagy. The metabolism of the extra-cellular matrix was also investigated. THE RESULTS: Dex increased intracellular ROS level, the expression of Akt, FOXO3 as well as autophagy flux in human chondrocytes. The expression of aggrecanases also increased after the treatment of Dex. Catalase, the ROS scavenger, suppressed Dex-induced up-regulation of autophagy flux and expression of aggrecanases and Akt. MK-2206 and LY294002, the PI3K/Akt inhibitors, repressed Dex-induced up-regulation of FOXO3. Silencing FOXO3 resulted in down-regulation of Dex-induced autophagy. Moreover, knockdown of FOXO3 increased Dex-induced apoptosis as well as ROS levels in chondrocytes. In addition, up-regulation of autophagy by Rapamycin resulted in decreasing ROS level in chondrocytes. CONCLUSION: Dex could advance the degenerative process in cartilage. Autophagy was induced in response to Dex-induced up-regulation of ROS via ROS/Akt/FOXO3 signal pathway.
26044064 Systemic adalimumab induces peripheral corneal infiltrates: a case report. 2015 Jun 6 BACKGROUND: Tumor necrosis factor-alpha inhibitors are widely used agents in the treatment of immune disorders such as rheumatoid arthritis and inflammatory bowel disease. Despite their anti-inflammatory action, paradoxical drug-induced inflammatory events have been occasionally associated with the use of infliximab, etanercept, and in a lesser extent adalimumab. However, eye involvement is uncommon and anterior uveitis is the only reported ocular adverse manifestation. It can be induced by etanercept, but has also been described during adalimumab therapy. We present here the first report of recurrent peripheral corneal infiltrates following subcutaneous injections of adalimumab. CASE PRESENTATION: A 34 year-old Caucasian woman with Crohn's disease presented to the emergency department with bilateral red eyes and discomfort 36 hours after she received her bimonthly dose of subcutaneous adalimumab. Examination revealed bilateral peripheral corneal infiltrates with characteristic features of immune infiltrates. Symptoms and infiltrates regressed after topical corticosteroid therapy, but recurred after each adalimumab injection over the following weeks. CONCLUSION: Paradoxical immune reactions associated with tumor necrosis factor-alpha inhibitors may result either from hypersensitivity mechanisms, or from immune-complex deposition via anti-adalimumab antibodies. Both mechanisms could explain this newly described manifestation. Care should be taken to search for corneal infiltrates in the event of red eye symptoms during adalimumab therapy since they respond to topical corticosteroids and do not necessarily prompt the discontinuation of the immunosuppressive therapy.
25993350 [10-Year Follow-Up of the NexGen CR Total Knee Prosthesis]. 2015 Oct BACKGROUND: The purpose of this study was to evaluate long-term clinical and radiological results as well as survival rates of the NexGen® CR posterior cruciate retaining prosthesis. PATIENTS AND METHODS: We evaluated a consecutive series of 761 total knee replacements performed on 716 patients from 1999 to 2001 at our institution. All patients had been recorded prospectively in our in-house arthroplasty register. Follow-up data were available for 379 patients at 10 years postoperatively. Functional outcome was evaluated using the Knee Society score. An additional radiographic evaluation was performed on 224 patients at 10 years. The mean age of the patients at the time of surgery was 71 years. 75 % of the patients were female, 25 % were male. Mean BMI of the patients was 29.2 kg/m(2). The preoperative diagnosis was osteoarthritis in 91 %, rheumatoid arthritis in 5,5 % and posttraumatic osteoarthritis in 2 %. Patella resurfacing was performed in 4 %. All components were cemented. RESULTS AND DISCUSSION: Mean Knee Society clinical score improved from 26.7 points preoperatively to 88.5 points at the time of the latest follow-up, and mean Knee Society function score improved from 48.3 to 55.2 points. Flexion improved from a mean of 106.7° preoperatively to 111.4° at 10 years. Patellofemoral pain was indicated by 66 % of the patients before surgery and 4 % at the latest follow-up. 96 % were satisfied with the result of the surgery at 10 years. Radiographic evaluation was performed on 224 patients at the time of the latest follow-up. 203 patients (91 %) had normal radiographic findings, 21 patients (9 %) showed pathological findings. Radiolucencies were seen in 18 patients on the AP view of the tibia, 1 patient had an additional femoral radiolucency. There was an osteolysis located in the lateral tibia seen in 1 patient and an occurrence of heterotopic ossification in another patient. One knee showed a patella subluxation. No patient had radiographic evidence of loosening. 17 knees had required revision surgery with exchange of at least one of the components up to 10 years after the index procedure. 5 of the patients had revision for a deep infection, 2 for periprosthetic fractures of the distal femur with loosening of the prosthesis, 1 for fracture of the proximal tibia due to osteoporosis, 4 for aseptic loosening, 3 for instability and 2 for severe pain. Kaplan-Meier survival of all components using revision for any reason as the end point was 97.8 % at 10 years. CONCLUSION: The good clinical and radiological long-term results as well as the satisfactory survival rate after total knee replacement with the NexGen CR® prosthesis are comparable with the results of other long-term studies using the NexGen CR® and assimilable prosthesis. Our results demonstrate that quality of life was improved by the implantation of the NexGen CR® prosthesis even a long time after the index procedure despite old age and comorbidity of the patients.
25910534 An in vivo and in vitro assessment of the anti-inflammatory, antinociceptive, and immunomo 2015 Jul 1 AIM: Clematis terniflora DC. has been widely used as a traditional Chinese medicine for the treatment of tonsillitis, rheumatoid arthritis, and prostatitis. Despite its widespread use in China, there are currently no studies systematically examined its therapeutic effects and mechanism of action. As such, the present study was conducted to evaluate the anti-inflammatory, antinociceptive, and immunomodulatory effects of C. terniflora DC. using rodent and cellular models. METHODS: The anti-inflammatory properties of the 70% ethanol eluted fraction of the 70% ethanol extract of C. terniflora DC. (EECTD) were evaluated using the xylene-induced ear swelling test, the carrageenan-induced edema model, and the cotton pellet granuloma method. Its antinociceptive activities were determined using both the acetic acid-induced writhing test and the hot plate assay. In parallel, we conducted an in vitro assay in LPS-induced RAW264.7 cells to examine the anti-inflammatory effects of EECTD and its purified form, aurantiamide acetate (AA) on inhibition of nitric oxide (NO) and prostaglandin E2 (PGE2) release. RESULTS: EECTD (300mg/kg) significantly reduced the number of writhing, extended the pain response latency, and suppressed xylene-induced ear swelling. Each EECTD treatment group also had significant inhibition of cotton granulation formation in addition to reduced carrageenan-induced paw edema. EECTD was also shown to alleviate signs of inflammation in histopathological paw sections. However, it had a less noticeable effect on mouse ear swelling in the delayed type hypersensitivity test. A purified compound was isolated from EECTD and its structure was identified as AA. In vitro experimental results showed that both EECTD and AA were able to significantly inhibit the release of pro-inflammatory cytokines NO and PGE2 on LPS-induced RAW264.7 cells. CONCLUSION: These results suggest that EECTD has significant anti-inflammatory and antinociceptive activities, partially related to one of the active substances identified as AA. We hypothesize that these effects are related to its ability to inhibit the production of cytokines NO and PGE2. However, further work will be needed to determine its exact mechanism of action.
25884411 Common synonymous variants in ABCA4 are protective for chloroquine induced maculopathy (to 2015 Mar 6 BACKGROUND: Chloroquine (CQ) and hydroxychloroquine (HCQ) are used to treat auto-immune related diseases such as rheumatoid arthritis (RA) or systemic lupus erythematosus. Both drugs however can cause retinal toxicity eventually leading to irreversible maculopathy and retinopathy. Established risk factors are duration and dosage of treatment while the involvement of genetic factors contributing to toxic maculopathy is largely unclear. To address the latter issue, this study aimed to expand on earlier efforts by (1) evaluating risk-altering variants known to be associated with age-related macular degeneration (AMD), a frequent maculopathy in individuals over 55 years of age, and (2) determining the contribution of genetic variants in the coding sequence of the ABCA4 gene. METHODS: The ABCA4 gene was analyzed by deep sequencing technology using a personal genome machine (Ion Torrent) with 200 bp read length. Assessment of AMD variants was done by restriction enzyme digestion of PCR products and TaqMan SNP genotyping. Effect sizes, p-values and confidence intervals of common variants were evaluated by logistic regression (Firth's bias corrected). To account for multiple testing, p-values were adjusted according to the false discovery rate. RESULTS: We found no effects of known AMD-associated variants on the risk of toxic maculopathy. In contrast, we report a statistically significant association of common variants in the ABCA4 gene with retinal disease, assessed by a score-based variance-component test (PSKAT = 0.0055). This association remained significant after adjustment for environmental factors like age and duration of medication and was driven by three common variants in ABCA4 (c.5682G > C, c.5814A > G, c.5844A > G), all conferring a reduced risk for toxic maculopathy. CONCLUSIONS: Our findings demonstrate that minor alleles of common genetic variants in ABCA4 significantly reduce susceptibility to develop toxic maculopathy under CQ treatment. A refined risk profile based on genetic and environmental factors may have implications for revised recommendations in CQ as well as HCQ treatment.
25734250 Organ specificity in autoimmune diseases: thyroid and islet autoimmunity in alopecia areat 2015 May CONTEXT: Multiple autoimmune diseases, such as autoimmunity against the thyroid gland and pancreatic islets, are often observed in a single patient. Although alopecia areata (AA) is one of the most frequent organ-specific autoimmune diseases, the association of AA with other autoimmune diseases and the genetic basis of the association remain to be analyzed. OBJECTIVE: The aim of this study was to clarify the similarities and differences in HLA and clinical characteristics of thyroid and islet autoimmunity in patients with AA. PARTICIPANTS: A total of 126 patients with AA were newly recruited. Anti-islet and antithyroid autoantibodies were tested, and genotypes of HLA genes were determined. RESULTS: Among the autoimmune diseases associated with AA, autoimmune thyroid disease was most frequent (10.0%), followed by vitiligo (2.7%) and rheumatoid arthritis (0.9%) but not type 1 diabetes (0.0%). The prevalence of thyroid-related autoantibodies in patients with AA was significantly higher than that in controls (TSH receptor antibody [TRAb]: 42.7% vs 1.2%, P = 1.6 × 10(-46); thyroid peroxidase antibody: 29.1% vs 11.6%; P = 1.7 × 10(-6)), whereas the prevalence of islet-related autoantibodies was comparable between patients with AA and control subjects. The frequency of DRB1*15:01-DQB1*06:02, a protective haplotype for type 1 diabetes, was significantly higher in TRAb-positive (12.8%, P = .0028, corrected P value [Pc] = .02) but not TRAb-negative (7.1%, not significant) patients with AA than in control subjects (4.5%). The frequency of DRB1*04:05-DQB1*04:01, a susceptible haplotype for type 1 diabetes, was significantly lower in patients with AA (TRAb-positive: 8.5%; TRAb-negative: 11.9%) than in those with type 1 diabetes (29.5%, Pc < .0003 and Pc < .0008, respectively). CONCLUSION: AA was associated with thyroid autoimmunity but not islet autoimmunity, which correlated with class II HLA haplotypes susceptible or resistant to each autoimmune disease.