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ID PMID Title PublicationDate abstract
29375397 The Cerebral Brain-Derived Neurotrophic Factor Pathway, Either Neuronal or Endothelial, Is 2017 Cognitive abilities are largely dependent on activation of cerebral tropomyosin-related kinase B receptors (TrkB) by brain-derived neurotrophic factor (BDNF) that is secreted under a bioactive form by both neurons and endothelial cells. In addition, there is mounting evidence for a link between endothelial function and cognition even though the underlying mechanisms are not well known. Therefore, we investigated the cerebral BDNF pathway, either neuronal or endothelial, in rheumatoid arthritis (RA) that combines both endothelial dysfunction (ED) and impaired cognition. Adjuvant-induced arthritis (AIA) in rats was used as a model of RA. Clinical inflammatory symptoms were evaluated from an arthritis score and brains were collected at day 31 ± 2 post-immunization. Neuronal expression of BDNF and TrkB phosphorylated at tyrosine 816 (p-TrkB) was examined in brain slices. Endothelial BDNF and p-TrkB expression was examined on both brain slices (hippocampal arterioles) and isolated cerebral microvessels-enriched fractions (vessels downstream to arterioles). The connection between endothelial nitric oxide (NO) and BDNF production was explored on the cerebrovascular fractions using endothelial NO synthase (eNOS) levels as a marker of NO production, N(ω)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) as a NOS inhibitor and glyceryl-trinitrate as a slow releasing NO donor. Brain slices displayed lower BDNF and p-TrkB staining in both neurons and arteriolar endothelial cells in AIA than in control rats. For endothelial cells but not neurons, a strong correlation was observed between BDNF and p-TrkB staining. Of note, a strong correlation was also observed between neuronal p-TrkB and endothelial BDNF staining. In cerebral microvessels-enriched fractions, AIA led to decreased BDNF and eNOS levels with a positive association between the 2 parameters. These effects coincided with decreased BDNF and p-TrkB staining in endothelial cells. The exposure of AIA cerebrovascular fractions to GTN increased BDNF levels while the exposure of control fractions to L-NAME decreased BDNF levels. Changes in the cerebral BDNF pathway were not associated with arthritis score. The present study reveals that AIA impairs the endothelial and neuronal BDNF/TrkB pathway, irrespective of the severity of inflammatory symptoms but dependent on endothelial NO production. These results open new perspectives for the understanding of the link between ED and impaired cognition.
29158925 Splenic Infarct and Pulmonary Embolism as a Rare Manifestation of Cytomegalovirus Infectio 2017 Cytomegalovirus (CMV) is a type of herpes infection that has a characteristic feature of maintaining lifelong latency within the host cell. CMV manifestations can cover a broad spectrum from fever to as severe as pancytopenia, hepatitis, retinitis, meningoencephalitis, Guillain-Barre syndrome, pneumonia, and thrombosis. Multiple case reports of thrombosis associated with CMV have been reported. Deep vein thrombosis or pulmonary embolism is more common in immunocompetent patients while splenic infarct is more common in immunocompromised patients. However, here we report a female patient on low-dose methotrexate for rheumatoid arthritis who presented with both pulmonary embolism and splenic infarct.
29032452 Treatment Outcomes with Biosimilars: Be Aware of the Nocebo Effect. 2017 Dec Over the years, biologic agents have proven their importance in the management of chronic autoimmune diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. Biosimilars, which are biologic medicines, are highly similar to approved biologic medicines, and are comprehensively developed and rigorously tested to ensure efficacy and safety are similar to the reference product. A broader armamentarium of biosimilars is expected to improve patients' access to safe and effective biologic medicines, thus offering benefits to healthcare systems around the globe. Here we consider the factors that may compromise the benefits of biosimilars being realized, including patient and physician perception of biosimilars, and an often overlooked factor, the nocebo effect, which is re-emerging with the widespread adoption of biosimilar medicines. We have also described a variety of strategies and recommendations that could help limit the nocebo effect. FUNDING: Biogen.
28299772 Immunology proves a great success for treating systemic autoimmune diseases - a perspectiv 2017 Jul Recent advances in the bioengineering of monoclonal antibodies (mAbs) have revolutionized the treatment of several immunological and rheumatic diseases. mAbs exhibit high specificity and affinity, and are very effective targeting agents, associated with minimal off-target adverse effects. Of several relevant immunological diseases, rheumatoid arthritis was the condition initially treated with mAbs, with great success. Currently, many immunological disorders are targeted and successfully treated using such novel approaches; these include inflammatory bowel diseases, multiple sclerosis, lupus and psoriasis. Today, the efforts of researchers in basic immunology (with a long history) have borne fruit; bioengineered mAbs are employed in clinical practice. In this brief review, I will describe the current and emerging therapeutic mAbs and molecular targeted agents, and discuss the future of the field, especially from the viewpoint of pharmacology.
29104284 JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. 2017 Dec The discovery of cytokines as key drivers of immune-mediated diseases has spurred efforts to target their associated signalling pathways. Janus kinases (JAKs) are essential signalling mediators downstream of many pro-inflammatory cytokines, and small-molecule inhibitors of JAKs (jakinibs) have gained traction as safe and efficacious options for the treatment of inflammation-driven pathologies such as rheumatoid arthritis, psoriasis and inflammatory bowel disease. Building on the clinical success of first-generation jakinibs, second-generation compounds that claim to be more selective are currently undergoing development and proceeding to clinical trials. However, important questions remain about the advantages and limitations of improved JAK selectivity, optimal routes and dosing regimens and how best to identify patients who will benefit from jakinibs. This Review discusses the biology of jakinibs from a translational perspective, focusing on recent insights from clinical trials, the development of novel agents and the use of jakinibs in a spectrum of immune and inflammatory diseases.
28679953 Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartila 2017 Jul 6 Today, it is known that autoimmune diseases start a long time before clinical symptoms appear. Anti-citrullinated protein antibodies (ACPAs) appear many years before the clinical onset of rheumatoid arthritis (RA). However, it is still unclear if and how ACPAs are arthritogenic. To better understand the molecular basis of pathogenicity of ACPAs, we investigated autoantibodies reactive against the C1 epitope of collagen type II (CII) and its citrullinated variants. We found that these antibodies are commonly occurring in RA. A mAb (ACC1) against citrullinated C1 was found to cross-react with several noncitrullinated epitopes on native CII, causing proteoglycan depletion of cartilage and severe arthritis in mice. Structural studies by X-ray crystallography showed that such recognition is governed by a shared structural motif "RG-TG" within all the epitopes, including electrostatic potential-controlled citrulline specificity. Overall, we have demonstrated a molecular mechanism that explains how ACPAs trigger arthritis.
28122760 The unclosing premature mortality gap in gout: a general population-based study. 2017 Jul OBJECTIVE: Gout, the most common inflammatory arthritis, is associated with premature mortality. Whether this mortality gap has improved over time, as observed in rheumatoid arthritis (RA), is unknown. METHODS: Using an electronic medical record database representative of the UK general population, we identified incident gout cases and controls between 1999 and 2014. The gout cohort was divided based on year of diagnosis into early (1999-2006) and late (2007-2014) cohorts. We compared the mortality rates and HRs, adjusting for potential confounders between the cohorts. We conducted sensitivity analyses among patients with gout who received at least one prescription for urate-lowering therapy, which has been found to have a validity of 90%. RESULTS: In both cohorts, patients with gout showed similar levels of excess mortality compared with their corresponding comparison cohort (ie, 29.1 vs 23.5 deaths/1000 person-years and 23.0 vs 18.8 deaths/1000 person-years in the early and late cohorts, respectively). The corresponding mortality HRs were 1.25 (95% CI 1.21 to 1.30) and 1.24 (95% CI 1.20 to 1.29), and the multivariable HRs were 1.10 (95% CI 1.06 to 1.15) and 1.09 (95% CI 1.05 to 1.13), respectively (both p values for interaction >0.72). Our sensitivity analyses showed similar findings (both p values for interaction >0.88). CONCLUSIONS: This general population-based cohort study indicates that the level of premature mortality among patients with gout remains unimproved over the past 16 years, unlike RA during the same period. This unclosing premature mortality gap calls for improved management of gout and its comorbidities.
28923775 Immunoadsorption using Immusorba TR and PH. 2017 Oct Immusorba TR (IM-TR) and PH (IM-PH) were developed as immunoadsorbents from nonbiological materials as affinity ligands for removal of pathogenic substances. The immunoadsorbents in IM-TR and IM-PH are immobilized on a polyvinyl alcohol gel with tryptophan and phenylalanine, respectively, as a ligand. IM-TR is mainly clinically applied to autoimmune neurological diseases such as myasthenia gravis, Guillain-Barré syndrome, and multiple sclerosis. IM-PH is also applied to neurological diseases but mainly to rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. Many autoantibodies with different specificities have been found to have similar affinity for the ligand of Immusorba, and it is expected that Immusorba will be used against more diseases and help to elucidate the pathogenesis of diseases via identification of unknown pathogenic substances adsorbed to Immusorba.
28840675 Spontaneous rupture of the digital extensor tendons of the hand in unrecognized carpal lun 2017 Mar Spontaneous rupture of the digital extensor tendons of the hand has been reported after Kienbocks disease, rheumatoid arthritis, Vaughan-Jackson syndrome, distal radial fracture. Rupture may also occur as a consequence of unrecognized carpal lunate fracture. We present a case report of a man affected with spontaneous rupture of the digital extensor tendons secondary to unrecognized carpal lunate fracture with partial dorsal dislocation. The edges of the tendon were debrided and sutured using a locked modified Kessler suture. A dynamic splinting cast was applied in moderate extension of the wrist. The aim of this case report is to highlight that in absence of a clear etiology for rupture of the extensor tendons of the hand, carpal lunate fracture, though rare, is an important cause of spontaneous extensor tendons rupture.
27381347 Methotrexate induced pneumatosis intestinalis under hemodialysis patient. 2017 Jan Pneumatosis intestinalis (PI) is a rare disorder characterized by the gas within the intestinal mucosa. This is the first report methotrexate (MTX) induced PI under hemodialysis (HD) patient. A 46-year-old man suffered rheumatoid arthritis and underwent HD at local HD center. After the initial induction of MTX, the patient showed epigastralgia and diarrhea. He was referred to our hospital and abdominal computed tomography showed significant large intestinal edema and free intraperitoneal air consistent with PI. Physicians should aware that MTX is contraindication drug for chronic kidney disease and high-flux HD may decrease MTX toxicity and oxidative stress, improving PI.
29074827 [Update on recent progress in vitamin D research. The effects of vitamin D in autoinflamma 2017 Various kinds of immune cells -including dendritic cells, macrophages, T cells and B cells- express the vitamin D receptor and 1α-hydroxylase(CYP27B1). In vitro studies have shown the anti-inflammatory effect of 1,25-dihydroxyvitamin D:the active form of vitamin D. As vitamin D deficiency spread in our society, epidemiological studies have established the association between vitamin D deficiency and incidence or progression of several inflammatory diseases, including rheumatoid arthritis(RA), systemic lupus erythematosus(SLE), and multiple sclerosis(MS). In addition, recently the property of vitamin D for treatment or prevention is debated. Here, we review the recent epidemiological evidence associated with vitamin D and inflammatory diseases, and describe the immunomodulatory effect of vitamin D underlying it.
29199167 Which diseases are risk factors for developing gastroesophageal reflux disease? 2017 Dec Although the pathophysiology of gastroesophageal reflux disease (GERD) remains unclear, it is accepted as a multifactorial disease. It is thought that some of the interventions that might cause alterations in the normal gastrointestinal tract anatomy and diseases that affect the lower esophageal sphincter, esophageal clearance, and stomach motility (gastric emptying) might lay a foundation for GERD development. Moreover, it is common knowledge that GERD might cause various extraesophageal symptoms and complications. A possible connection between GERD and sarcoidosis, amyloidosis, hypothyroidism, rheumatoid arthritis, mixed connective tissue disorders, Sjögren's syndrome, systemic sclerosis, diabetes mellitus, cholecystectomy, sleeve gastrectomy, sleep apnea syndrome, chronic obstructive pulmonary disease, and asthma were summarized in this literature review.
29018757 Macular edema might be a rare presentation of hydroxychloroquine-induced retinal toxicity. 2017 Jan The aim of this study is to report a rare case of macular edema as a presentation of hydroxychloroquine-related retinal toxicity. We presented a case of a 46-year-old female patient using hydroxychloroquine for underlying rheumatoid arthritis (RA) with blurred vision over the left eye. Uveitis and macular edema were found initially. Systemic survey did not reveal any other etiology. Topical corticosteroid was given under the impression of RA-related uveitis. The uveitis resolved 1 week later, but macular edema persisted in spite of treatment. Under the suspicion of drug-related complication, we try to discontinue hydroxychloroquine. Her symptoms improved gradually after cessation of hydroxychloroquine, and further serial image study confirmed subsiding of the macular edema without any further treatment. Except the well-known signs of the retinal toxicity, macular edema might be a rare presentation of hydroxychloroquine-related retinal toxicity.
28785483 Peripheral Ulcerative Keratitis Associated with Autoimmune Disease: Pathogenesis and Treat 2017 Peripheral ulcerative keratitis (PUK) is type of crescent-shaped inflammatory damage that occurs in the limbal region of the cornea. PUK is always combined with an epithelial defect and the destruction of the peripheral corneal stroma. PUK may have a connection to systemic conditions, such as long-standing rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Wegener granulomatosis (WG), relapsing polychondritis, classic polyarteritis nodosa and its variants, microscopic polyangiitis, and Churg-Strauss syndrome. However, the most common connection is with RA, which is also the focus of this review. The pathogenesis of PUK is still unclear. It is thought that circulating immune complexes and cytokines exert an important influence on the progression of this syndrome. Treatment is applied to inhibit certain aspects of PUK pathogenesis.
28583053 The Use of MDHAQ/RAPID3 in Different Rheumatic Diseases A Review of the Literature. 2017 Apr Composite indices are frequently used for most rheumatic diseases because of the absence of a single "gold standard" measure applicable to all individual patients with a specific diagnosis. Some of the most commonly used composite indices in rheumatology are too complex and time-consuming for usual clinical care. Nowadays, there is an increasing focus on patient-centered care, and the use of patient-reported outcome measures (PROMs) might offer a patient-friendly, time and cost efficient strategy to monitor chronic diseases. Although initially developed for rheumatoid arthritis (RA), a multidimensional health assessment questionnaire (MDHAQ), which only includes PROMs, has been found informative in many rheumatic diseases. Assessment of a patient with any rheumatic disease requires information beyond what is found on a patient questionnaire, including a careful history and physical examination, as well as relevant laboratory tests and imaging studies, to formulate an optimal treatment plan for each individual patient. Nonetheless, documentation of patient clinical status and change in status may be best accomplished through patient questionnaires. This review summarizes all the evidence relevant to the use of MDHAQ in other rheumatic diseases apart from RA.
28530766 Right Ring Finger Volar Mass in a 14-Year-Old Boy. 2017 Sep 1 A trigger digit is relatively uncommon in adolescents and often has a different etiology in that age group vs adults. In the pediatric population, trigger digits frequently arise from a variety of underlying anatomic situations, including thickening of the flexor digitorum superficialis or flexor digitorum profundus tendons, an abnormal relationship between the flexor digitorum superficialis and flexor digitorum profundus tendons, a proximal flexor digitorum superficialis decussation, or constriction of the pulleys. In addition, underlying conditions such as mucopolysaccharidosis, juvenile rheumatoid arthritis, Ehlers-Danlos syndrome, and central nervous system disorders such as delayed motor development have been associated with triggering. Less commonly, triggering secondary to intratendinous or peritendinous calcifications or granulations has been described, which is what occurred in the current case. This report describes a case of tenosynovitis with psammomatous calcification treated with excision of the mass from the flexor digitorum superficialis tendon and release of both the A1 and palmar aponeurosis pulleys in an adolescent patient. [Orthopedics. 2017; 40(5):e918-e920.].
28088881 An industry update: the latest developments in therapeutic delivery. 2017 Feb This Industry Update covers the period from 1 October through to 31 October 2016, and is based on information sourced from company press releases, scientific literature, patents and various news websites. The month saw several news items covering drug-delivery devices, including a new sensor to monitor and support the use of inhalers; launch in the UK of a new autoinjector for Cimzia(®), UCB's rheumatoid arthritis drug; and approval of Roche's Lucentis(®) in a prefilled syringe. Research was also published to show the value of continuous blood pressure monitoring in dementia management. Astellas announced the acquisition of German pharmaceutical company Ganymed while Sunovion completed its purchase of Cynapsus. A new EU-funded collaboration was announced looking at the value of PET-based biomarkers in Alzheimer's disease. GSK gained USA approval for its shingles vaccine, but Novo Nordisk and Sanofi received complete response letters from the US FDA, requiring further information before regulatory review of their drug submissions can be completed. The UK's NICE concluded that a drug marketed by BMS to treat a common type of lung cancer was not cost-effective and Cornell University announced results showing that its nanoparticle technology, originally developed as a tumor biomarker, could be effective in directly treating the disease.
28816770 Prevalence of Disability in Patients With Musculoskeletal Pain and Rheumatic Diseases in a 2017 Sep OBJECTIVE: The aim of this study was to determine the prevalence of disability in patients with musculoskeletal pain and rheumatic diseases in Cuenca, Ecuador. METHODS: We performed a cross-sectional analytical study with randomized sampling in 4877 subjects, from urban and rural areas. COPCORD (Community Oriented Program for Control of Rheumatic Diseases)-validated questionnaire was administered house-to-house to identify subjects with nontraumatic musculoskeletal pain and rheumatic diseases. The subjects were assessed by rheumatologists for diagnostic accuracy, and the Health Assessment Questionnaire Disability Index was administered to assess functional capacity. A logistic regression analysis was conducted to determine the association of rheumatic diseases with functional disability. RESULTS: Functional disability was found in 221 subjects (73.1% women), with mean age 62 (SD, 18.2) years, residing in rural areas (201 [66.5%]), with education of 6.9 (SD, 5.3) years, and of low income (77 [47.2%]). The value of HAQ-DI was a mean of 0.2 (0-2.9). The real prevalence of physical disability was 9.5%. Moderate and severe disability predominated in activities such as kneeling (4.9% and 3.3%), squatting (4.8% and 2.7%), and leaning to pick up objects (3.7% and 0.9%), respectively. Rheumatic diseases associated with physical disabilities were knee osteoarthritis (95 [31.4%]) and hand osteoarthritis (69 [22.8%]), mechanical low-back pain (43 [14.2%]), fibromyalgia (27 [9.5%]), and rheumatoid arthritis (11 [3.6%]; P < 0.001). CONCLUSIONS: Physical disability was associated with older age, female sex, rural residence, lower education, and lower income. Moderate and severe disability predominated in the dimensions of kneeling, squatting, and picking up objects. Rheumatic diseases associated with disability were hand and knee osteoarthritis, back pain, fibromyalgia, and rheumatoid arthritis.
28744810 Krüppel-like factor 4 regulates the expression of inducible nitric oxide synthase induced 2018 Jan Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, has been implicated in the inflammation mediated by macrophages and endothelial cells by regulating the expression of inflammatory mediators. Here, we investigated whether KLF4 affects the expression of inducible nitric oxide synthase (iNOS), an important inflammatory mediator, in the human RA fibroblast-like synovial cell line MH7A. A pcDNA3.1-KLF4 plasmid or short interfering RNA KLF4 was transfected into MH7A cells, and the iNOS expression and nitric oxide (NO) production were analyzed by quantitative PCR, immunoblotting, and nitrite measurement. The iNOS promoter activity was determined by luciferase assay. The results showed overexpression of KLF4 increased iNOS expression and NO production in the presence or absence of TNF-α. Conversely, KLF4 knockdown markedly reduced iNOS expression and NO production induced by TNF-α. KLF4 activated the transcription activity of iNOS promoter in MH7A cells stimulated by TNF-α. This study indicates that KLF4 is important for regulating the expression of iNOS by TNF-α in human synoviocytes.
27535275 [Differences in chronic back pain and joint disorders among health insurance funds : Resul 2017 Apr BACKGROUND: Health services research uses increasingly data from health insurance funds. It is well known that the funds differ with regard to sociodemographic characteristics and morbidity. It is uncertain if there are also differences in the prevalence of musculoskeletal disorders. OBJECTIVE: To compare the sociodemographic characteristics in various health insurance funds and the prevalence of joint disorders and chronic back pain. METHOD: The 30(th) wave (2013) of the German Socioeconomic Panel served as a database. Average age, sex distribution, nationality, education, and employment status were evaluated according to the health insurance funds. The prevalence of joint disorders and chronic back pain were also stratified according to the insurance funds and standardized according to age and sex. RESULTS: A total of 19,146 participants were included. Most participants (4,934) were insured by AOK, followed by BKK (2,632) and BARMER GEK (2,398). There were huge differences among the health insurance funds with regard to the sociodemographic characteristics. For example, the proportion of unemployed insurants was between 33.3 % (IKK) and 50.6 % (AOK). The prevalence of joint disorders standardized according to age and sex (20.7 %; 95 % CI: 20.1-21.3) was between 17.4 % (95 % CI: 15.8-19.0; PKV) and 22.4 % (95 % CI: 21.1-23.6; AOK). The prevalence of chronic back pain (18.0 %; 95 % CI: 17.4-18.5) was between 13.5 % (95 % CI: 12.2-14.9; PKV) and 20.6 % (95 % CI: 19.4-21.8; AOK). CONCLUSION: There are differences in the prevalence of musculoskeletal disorders among health insurance funds. The extrapolation of analyses of one health insurance fund to the German population is thus limited.