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ID PMID Title PublicationDate abstract
28317489 Ankylosing Spondylitis and Pregnancy: A Literature Review. 2017 BACKGROUND: Ankylosing Spondylitis (AS) is the prototype of a group of systemic rheumatic diseases collectively referred to as Spondylarthitides (SpA). It has now become clear that AS is not as rare as previously thought and, although it has an early onset in life affecting patients in their reproductive years, it has not been proved to adversely affect fertility in females. OBJECTIVE: The aim of this review is to summarize all the recent data on AS and pregnancy in terms of fertility, disease course and pregnancy outcome from a clinical perspective. METHOD: A literature research was conducted based on the following medical databases: Pubmed/ Medline and the Cochrane Library. We searched for randomized controlled studies, casecontrol studies, cohort studies, patient and drug registers in relation to pregnancy and AS. RESULTS: The existing data do not support a causal relationship between AS and infertility. The state of pregnancy is not associated with reduced disease activity in patients with AS. Additionally, AS tends to adversely affect health-related quality of life during pregnancy, in comparison with normal population and patients with rheumatoid arthritis. As far as the obstetrical outcome is concerned, there is no consensus on the significant association between AS and specific pregnancy, delivery and fetal complications. CONCLUSION: Previous studies are highly heterogenous and mainly retrospective and thus, the existing data are controversial and inconclusive. Subsequent studies are required to enlighten our knowledge on the interaction between AS and pregnancy.
27755179 Imaging in knee osteoarthritis. 2017 Jan PURPOSE OF REVIEW: Osteoarthritis is the most prevalent and disabling disease still necessitating research in pathogenic mechanisms, predictors of disease progression and responsive techniques to detect the slow structural changes within a short time frame. In this scenario, imaging modalities are essential. With recent advancements in technology and availability of large longitudinal datasets, tremendous advances are occurring. The present review discusses and summarizes recent original publications in this area. RECENT FINDINGS: MRI has been the most popular modality used to evaluate the different roles of structural disorders in incident knee osteoarthritis, to compare predictability of individual features of semiquantitative scores for knee replacement and to formulate different disease progression models. More ultrasound studies have been published, including the proposed semiquantitative scoring system by the Outcome Measures in Rheumatoid Arthritis Clinical Trial group. SUMMARY: As more advanced emerging technologies are developed in imaging, there are great opportunities to formulate new incident and prediction osteoarthritis models and to discover tissue-targeted disease-modifying drugs.
29312536 The shared and specific mechanism of four autoimmune diseases. 2017 Dec 12 Interaction between genetic and epigenetic mechanisms may lead to autoimmune diseases. The features of these diseases show familial aggregation. The generality and specificity are keys to studying pathogenesis and etiology of them. This research integrated data of genetics and epigenetics, to find disease-related genes based on the levels of expression and regulation, and explored then to the shared and specific mechanism of them by analyzing shared and specific pathways of common four autoimmune diseases, including Type 1 Diabetes Mellitus (T1D), Multiple Sclerosis (MS), Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE). The results showed that Lysosome and Fc gamma R-mediated phagocytosis are shared pathways of the four diseases. It means that the occurrence and development of them may associate with lysosomes and phagocytosis. And there were 2 pathways are shared pathways of three diseases, ribosome pathway associated with susceptibility to MS, RA and SLE, and Pathogenic Escherichia coli infection associated with susceptibility to T1D, MS and RA; 9 pathways are shared pathways of two diseases. The corporate underlying causes of these diseases may be these shared pathways activated. Furthermore, we found that T1D-related specific pathways (Insulin signaling,etc.) were 9, MS (Proteasome,etc.) is also 9, RA and SLE is 10 and 6 respectively. These pathways could help us to reveal shared and specific mechanisms of the four diseases.
29230210 Checkpoint Blockade Toxicity and Immune Homeostasis in the Gastrointestinal Tract. 2017 Monoclonal antibodies targeting the regulatory immune "checkpoint" receptors CTLA-4, PD-1, and PD-L1 are now standard therapy for diverse malignancies including melanoma, lung cancer, and renal cell carcinoma. Although effective in many patients and able to induce cures in some, targeting these regulatory pathways has led to a new class of immune-related adverse events. In many respects, these immune toxicities resemble idiopathic autoimmune diseases, such as inflammatory bowel disease, autoimmune hepatitis, rheumatoid arthritis, and vitiligo. Understanding the pathogenesis of these immune toxicities will have implications not only for care of patients receiving checkpoint blockade but may also provide critical insights into autoimmune disease. The gastrointestinal (GI) mucosa is arguably the most complex barrier in the body, host to a diverse commensal microflora and constantly challenged by ingested foreign proteins both of which must be tolerated. At the same time, the GI mucosa must defend against pathogenic microorganisms while maintaining sufficient permeability to absorb nutrients. For these reasons, regulatory cells and receptors are likely to play a central role in maintaining the gut barrier and GI toxicities, such as colitis and hepatitis are indeed among the most common side effects of CTLA-4 blockade and to a lesser extent blockade of PD-1 and PD-L1. High-dose corticosteroids are typically effective for management of both checkpoint colitis and hepatitis, although a fraction of patients will require additional immune suppression such as infliximab. Prompt recognition and treatment of these toxicities is essential to prevent more serious complications.
29193951 [Disseminated tuberculosis in a patient with overlap syndrome, challenges in preventing]. 2017 Sep Patients with autoimmune rheumatic diseases are at increased risk for developing infections and these are associated with increased morbidity and mortality from these diseases, especially in patients with systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis and autoimmune inflammatory myopathies. The objective of this paper is to address the challenges in detecting latent tuberculosis in immunosuppressed patients and the initiation of prophylactic treatment because currently there are no well-defined guidelines indicating what action to take for detection and treatment; so far the available scientific evidence is scarce and some methodological shortcomings.
28392952 Clinical Implications for the Timely Diagnosis of Mycobacterium marinum in the Age of Biol 2017 Mycobacterium marinum infections typically present as cutaneous nodular lesions with a sporotrichoid lymphatic spread on extensor surfaces of extremities. The natural history of this infection can be altered if the host is immunosuppressed, leading to disseminated presentations. A detailed exposure history and high degree of suspicion for this indolent pathogen are often required for the correct diagnosis of this disease. We present a case of a 67-year-old male misdiagnosed with seronegative rheumatoid arthritis presenting with rheumatic nodules. Initiation of chronic immunosuppressant therapy including biologic monoclonal antibodies resulted in the exacerbation of initially localized disease to broadly disseminated lymphatic, joint, and myotendinous granulomatous disease and led to delay in the correct diagnosis. Cessation of immunosuppressants, with a prolonged course of antimicrobial therapy and multiple surgical debridements were required for cure.
28108765 SCORE study: quality indicators for rheumatology nursing clinics. 2017 Mar Nursing clinics in rheumatology (NCR) are organizational care models that provide care centred within the scope of nurses abilities. To analyse patients differences in the knowledge of the disease, adherence to the treatment, quality indicators of the Rheumatology Departments included quality perceived by the patients with and without NCR. National multicenter observational prospective cohort study 1 year follow-up, comparing patients attending rheumatology services with and without NCR. NCR was defined by the presence of: (1) office itself; (2) at least one dedicated nurse; (3) its own appointment schedule, and (4) phone. Variables included were (baseline and 12 months) Batalla, Haynes-Sackett, Morisky-Green and quality perceived tests. In addition, another specific questionnaire was drawn up to collect the healthcare, teaching and research activities of each Rheumatology Department. A total of 393 patients were included; 181 NCR and 212 not NCR, corresponding to 39 units, 21 with NCR and 18 without NCR (age 53 ± 11.8 vs 56 ± 13.5 years). Significant differences in favour of the NCR group were found in Haynes-Sackett (p = 0.033) and Morisky-Green (p = 0.03) tests in the basal visit. Significant differences were found in questions about "the courtesy and/or kindness received by the nurse", being "good or very good" in greater proportion in the NCR group. The publications from the last 5 years were significantly higher in the NCR group in both, national (p = 0.04) and international (p = 0.03) journals. A higher research activity and quality perceived by the patients are observed in the Rheumatology Departments with NCR.
29264078 Disseminated Mycobacterium intracellulare infection with multiple abscesses on extremities 2017 Dec A 78-year-old Japanese woman with rheumatoid arthritis was admitted to our hospital due to fever. She had been prescribed prednisolone and bucillamine. Computed tomography revealed abscesses on extremities. M. intracellulare was cultured from her calcaneus osteomyelitis, and this result pointed to a disseminated mycobacterial infection. We drained the abscesses and found M. intracellulare. We started antimycobacterial agents, but the patient died finally. Disseminated mycobacterial infection is rare but critical, and the possibility of such an infection in an immunocompromised patient should be a prime consideration when choosing appropriate drugs and surgical approaches.
29201039 Multitemporal Volume Registration for the Analysis of Rheumatoid Arthritis Evolution in th 2017 This paper describes a method based on an automatic segmentation process to coregister carpal bones of the same patient imaged at different time points. A rigid registration was chosen to avoid artificial bone deformations and to allow finding eventual differences in the bone shape due to erosion, disease regression, or other eventual pathological signs. The actual registration step is performed on the basis of principal inertial axes of each carpal bone volume, as estimated from the inertia matrix. In contrast to already published approaches, the proposed method suggests splitting the 3D rotation into successive rotations about one axis at a time (the so-called basic or elemental rotations). In such a way, singularity and ambiguity drawbacks affecting other classical methods, for instance, the Euler angles method, are addressed. The proposed method was quantitatively evaluated using a set of real magnetic resonance imaging (MRI) sequences acquired at two different times from healthy wrists and by choosing a direct volumetric comparison as a cost function. Both the segmentation and registration steps are not based on a priori models, and they are therefore able to obtain good results even in pathological cases, as proven by the visual evaluation of actual pathological cases.
28875003 Inhibition of Angiogenesis: A Novel Effect of Zataria Multiflora. 2017 Apr 1 Background: Angiogenesis, the formation of new blood vessels from preexisting ones, is among the most important physiological and pathological processes that occur in the body. Under pathological conditions such as tumor growth, psoriasis, corneal neovascularization and rheumatoid arthritis, angiogenesis is substantial for the development of the disease. Zataria multiflora is a member of the Labiatae family with a vast range of traditional uses which has been long known and applied in Iran old medicine. The aim of this study was the evaluation of anti-angiogenic potential of Zataria multiflora. Materials and Methods: In this study, human umbilical vein endothelial cells (HUVECs) were isolated from newborn umbilical veins and then cultured for cytotoxicity (LDH test) assay. Regarding LDH results, following tests such as angiogenesis (cytodex-3 micro carrier) and migration (wound healing) tests were designed. Results: The cytotoxicity assays showed no toxicity of Z.multiflora toward HUVECs in the range of 10-450µg/mL of the extract. This extract was also able to inhibit angiogenesis and migration at 200µg/mL. Conclusion: Our data clearly demonstrated an inhibitory effect of Z. multiflora on angiogenesis and migration of HUVECs. Z. multiflora could be introduced as a significant angiogenesis inhibitor for angiogenesis-dependent diseases in further complementary studies.
28258476 Psychomotor Agitation Following Treatment with Hydroxychloroquine. 2017 Dec We describe the case of an elderly woman with elderly-onset rheumatoid arthritis, where the use of 4 mg/kg/day of hydroxychloroquine (HCQ) was followed by the onset of psychomotor agitation with marked physical and verbal violence towards her partner, including throwing objects at her partner. No disturbance in sleep and no anxiety, nervousness, or irritability had emerged before the onset of her psychomotor agitation. The disappearance of agitation following targeted pharmacologic intervention and HCQ interruption, its re-onset after reintroduction of the drug, and the high score (9) of Naranjo's algorithm are surely linked to the existence of a causal relationship between HCQ and psychomotor agitation. HCQ may produce undesirable effects on the central nervous system, mainly irritability, nervousness, emotional changes, and nightmares. To the best of our knowledge, there are only a few case reports of psychosis due to HCQ. No favoring condition such as pharmacokinetic interactions or a personal and family psychiatric history was present in our patient. The neuropsychiatric manifestations we observed could be considered a bizarre-type adverse drug reaction linked to an individual's hypersensitivity.
28163705 Vitamin D in Autoimmunity: Molecular Mechanisms and Therapeutic Potential. 2016 Over the last three decades, it has become clear that the role of vitamin D goes beyond the regulation of calcium homeostasis and bone health. An important extraskeletal effect of vitamin D is the modulation of the immune system. In the context of autoimmune diseases, this is illustrated by correlations of vitamin D status and genetic polymorphisms in the vitamin D receptor with the incidence and severity of the disease. These correlations warrant investigation into the potential use of vitamin D in the treatment of patients with autoimmune diseases. In recent years, several clinical trials have been performed to investigate the therapeutic value of vitamin D in multiple sclerosis, rheumatoid arthritis, Crohn's disease, type I diabetes, and systemic lupus erythematosus. Additionally, a second angle of investigation has focused on unraveling the molecular pathways used by vitamin D in order to find new potential therapeutic targets. This review will not only provide an overview of the clinical trials that have been performed but also discuss the current knowledge about the molecular mechanisms underlying the immunomodulatory effects of vitamin D and how these advances can be used in the treatment of autoimmune diseases.
28024126 Janus kinase (JAK) inhibitors for the treatment of skin and hair disorders: a review of li 2017 Sep Janus kinase family (JAKs) has recently attracted the attention of many researchers, and several JAK inhibitor drugs have been developed targeting different members of the JAK family. Tofacitinib and ruxolitinib are US FDA approved drugs in this family for rheumatoid arthritis and myeloproliferative diseases, respectively. Dysregulation of JAK/STAT pathway is also involved in many skin diseases, specifically inflammatory disorders. The JAK/STAT signaling pathway and its involvement in skin diseases are overviewed in this study. We also review clinical studies of JAK inhibitors in field of dermatology, including psoriasis, atopic dermatitis, alopecia areata and vitiligo. Although the available evidence shows promising results, it is still too early to draw a firm conclusion about the place of these drugs in dermatological treatment.
29019639 Spine Conditions: Cervical Spine Conditions. 2017 Oct There are a variety of causes of neck pain, including trauma and degenerative changes. The history of onset helps to direct evaluation, including the need for imaging or ancillary testing. Patterns of pain, weakness, and other specific physical examination findings also aid in diagnosis. Management of most soft tissue injuries involves early mobilization, whereas fractures are managed based on patterns of instability. Acute spinal cord injury requires emergent care, to include possible decompressive surgery. The role of hypothermia and corticosteroids in these patients remains unclear. Cervical radiculopathy (eg, disk herniation, arthritic changes) can be managed conservatively in most patients. Central cord compression, or myelopathy, often is overlooked but is a common condition among older patients. Although certain patients may benefit from surgery, many have a stable course or slow progression that can be managed nonsurgically. Rheumatoid arthritis can have significant effects on the cervical spine. Patients with inflammatory conditions may improve with steroids, nonsteroidal anti-inflammatory drugs, or biologic drugs, but these drugs rarely have lasting benefit in degenerative conditions. Stretching, strengthening, and other physical therapy modalities have been shown to be helpful for patients with chronic and acute but stable neck conditions.
28961706 Genome-wide association studies using a penalized moving-window regression. 2017 Dec 15 MOTIVATION: Genome-wide association studies (GWAS) have played an important role in identifying genetic variants underlying human complex traits. However, its success is hindered by weak effect at causal variants and presence of noise at non-causal variants. In an effort to overcome these difficulties, a previous study proposed a regularized regression method that penalizes on the difference of signal strength between two consecutive single-nucleotide polymorphisms (SNPs). RESULTS: We provide a generalization to the afore-mentioned method so that more adjacent SNPs can be incorporated. The choice of optimal number of SNPs is studied. Simulation studies indicate that when consecutive SNPs have similar absolute coefficients our method performs better than using LASSO penalty. In other situations, our method is still comparable to using LASSO penalty. The practical utility of the proposed method is demonstrated by applying it to Genetic Analysis Workshop 16 rheumatoid arthritis GWAS data. AVAILABILITY AND IMPLEMENTATION: An implementation of the proposed method is provided in R package MWLasso. CONTACT: kai-wang@uiowa.edu.
28593060 Fracture of the Tibial Baseplate 16 Years after Miller-Galante II Total Knee Arthroplasty. 2017 We report a rare case of tibial baseplate fracture of Miller-Galante II (MG II) prosthesis. We examine the factors that may cause such late fracture and review the literature on radiographic analysis and retrieval studies. A 76-year-old woman, who had undergone bilateral MG II total knee arthroplasty due to rheumatoid arthritis 16 years earlier, presented to our department with a 3-month history of left knee pain. Plain radiographs revealed severe distortion of the medial tibial component. During revision knee arthroplasty, we observed severe metallosis in the knee joint, polyethylene insert deformation, and posteromedial coronal baseplate fracture. After removal of the fractured tray, a bone deficit due to osteolysis was noted. The revision prosthesis (LCCK, Zimmer-Biomet) was implanted uneventfully. Four months after revision surgery, the patient was ambulating and had no complications. The implants on the right side had survived without complications for 17 years. We speculate that the primary causative factor of the fatigue fracture of the base plate due to loss of bony support most likely secondary to osteolysis was varus malalignment at primary implantation. This case highlights the importance of paying close attention to the correct alignment of each component at primary implantation.
29197623 Dual effects of sulfasalazine on rat sperm characteristics, spermatogenesis, and steroidog 2018 Mar 1 There are reports of sulfasalazine (Salazosulfapyridine; SASP)-induced reproductive toxicity, but there it is not known whether the SASP molecule or its intestinal metabolites are responsible for this effect. Rats received SASP (150, 300, and 600mg/kg) for 60 consecutive days (in vivo). Additionally, epididymal sperm was isolated and incubated with SASP (10μM-1600μM) (in vitro). Markers of oxidative stress, mitochondrial function, and sperm functionality, along with testis histopathology as well as several steroidogenic genes and proteins, including steroidogenic acute regulatory (StAR) protein, cytochrome P450 side chain cleavage enzyme (P450scc; Cyp11a), 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD) were measured. SASP toxicity was evident as shown by severe testicular histopathological alterations, along with poor sperm parameters and increased markers of oxidative stress. Plasma testosterone level and steroidogenesis-related gene and protein (StAR, 3-beta-HSD, 17-beta-HSD) expressions, as well as mitochondrial membrane potential, were significantly decreased at high doses of SASP (in vivo). Interestingly, in vitro treatment of sperm with SASP not only caused no significant detrimental effect on rat sperm but also increased parameters of sperm functionality and decreased markers of oxidative stress. SASP had paradoxical actions on the rat sperm in these experimental models. The findings might be useful in understanding the mechanism(s) of SASP-induced reproductive toxicity. The present findings have opened a new molecular window into the relationship between disrupted steroidogenesis and mammalian reproduction indices and also are vital regarding clinical administration of SASP and human reproductive health.
28948984 Scoring ultrasound synovitis in rheumatoid arthritis: a EULAR-OMERACT ultrasound taskforce 2017 OBJECTIVES: To test the reliability of new ultrasound (US) definitions and quantification of synovial hypertrophy (SH) and power Doppler (PD) signal, separately and in combination, in a range of joints in patients with rheumatoid arthritis (RA) using the European League Against Rheumatisms-Outcomes Measures in Rheumatology (EULAR-OMERACT) combined score for PD and SH. METHODS: A stepwise approach was used: (1) scoring static images of metacarpophalangeal (MCP) joints in a web-based exercise and subsequently when scanning patients; (2) scoring static images of wrist, proximal interphalangeal joints, knee and metatarsophalangeal joints in a web-based exercise and subsequently when scanning patients using different acquisitions (standardised vs usual practice). For reliability, kappa coefficients (κ) were used. RESULTS: Scoring MCP joints in static images showed substantial intraobserver variability but good to excellent interobserver reliability. In patients, intraobserver reliability was the same for the two acquisition methods. Interobserver reliability for SH (κ=0.87) and PD (κ=0.79) and the EULAR-OMERACT combined score (κ=0.86) were better when using a 'standardised' scan. For the other joints, the intraobserver reliability was excellent in static images for all scores (κ=0.8-0.97) and the interobserver reliability marginally lower. When using standardised scanning in patients, the intraobserver was good (κ=0.64 for SH and the EULAR-OMERACT combined score, 0.66 for PD) and the interobserver reliability was also good especially for PD (κ range=0.41-0.92). CONCLUSION: The EULAR-OMERACT score demonstrated moderate-good reliability in MCP joints using a standardised scan and is equally applicable in non-MCP joints. This scoring system should underpin improved reliability and consequently the responsiveness of US in RA clinical trials.
28988197 Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansopraz 2018 Jun OBJECTIVE: To assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use. DESIGN: A phase 3, 24-week, multicenter, randomised, double-blind (DB), active-controlled study, followed by a phase 3, ≥28 week, multicenter, single-blind, parallel-group extension study (EXT) in outpatients (n=642) receiving long-term NSAID therapy who are at risk of PU recurrence. The patients received vonoprazan (10 mg or 20 mg) or lansoprazole 15 mg once daily. For DB, non-inferiority of the proportion of patients with recurrent PU within 24 weeks was analysed by Farrington and Manning test (significance level 2.5%, non-inferiority margin 8.3%; primary endpoint), recurrent PU within 12 weeks, bleeding and time-to-event of PU (secondary endpoint) and treatment-emergent adverse events (TEAEs). For EXT, TEAEs (primary endpoint), recurrent PU and safety (secondary) were assessed up to 104 weeks for patients in the extension study. RESULTS: The non-inferiority of vonoprazan 10 mg and 20 mg to lansoprazole 15 mg was verified (percentage difference -2.2%,95% CI -6.2% to 1.8%, p<0.001; -2.1%,95% CI -6.1% to 2.0%, p<0.001, respectively). The proportion of patients with endoscopically confirmed recurrent PU within 24 weeks was 3.3%, 3.4% and 5.5%, for vonoprazan 10 mg, 20 mg and lansoprazole 15 mg, respectively. No significant safety concerns were identified. CONCLUSION: The non-inferiority of vonoprazan (10 and 20 mg) was verified in patients receiving long-term NSAIDs in DB; it was effective and well tolerated in EXT for longer than 1 year, with a safety profile similar to lansoprazole (15 mg). TRIAL REGISTRATION NUMBERS: NCT01452750, NCT01456260; Results.
27854054 Impact of Treatment-Related Beliefs on Medication Adherence in Immune-Mediated Inflammator 2017 Jan INTRODUCTION: Medication adherence is critical in chronic immune-mediated inflammatory diseases (IMIDs) and could be affected by patients' treatment-related beliefs. The objective of this study was to determine beliefs about systemic medications in patients with IMIDs and to explore the association of those beliefs and other factors with adherence. METHODS: This was a multi-country, cross-sectional, self-administered survey study. Included were adults diagnosed with one of six IMIDs receiving conventional systemic medications and/or tumor necrosis factor inhibitors (TNFi). Patients' necessity beliefs/concerns towards and adherence to treatments were assessed by the Beliefs about Medicines Questionnaire and four-item Morisky Medication Adherence Scale. Correlation of patients' beliefs about treatment and other factors with adherence were evaluated by multivariable regression analyses. RESULTS: Among studied patients (N = 7197), 32.0% received TNFi monotherapy, 27.7% received TNFi-conventional combination therapy, and 40.3% received conventional medications. Across IMIDs, high adherence to systemic treatment was more prevalent in TNFi groups (61.3-80.7%) versus corresponding conventional treatment groups (28.4-64.7%). In at least four IMIDs, greater perception of the illness continuing forever (P < 0.001), of the treatment helping (P < 0.001), and more concerns about the illness (P < 0.01), but not clinical parameters, were associated with higher treatment necessity beliefs. Higher treatment necessity beliefs, older age, Caucasian race, and TNFi therapy were associated with high medication adherence in at least four IMIDs. CONCLUSIONS: Treatment necessity beliefs were higher than concerns about current medication in patients with IMID. Illness perceptions had a greater impact on treatment necessity beliefs than clinical parameters. Older age, greater treatment necessity beliefs, and TNFi therapy were associated with high self-reported medication adherence in at least four IMIDs. TRIAL REGISTRATION: ACTRN12612000977875. FUNDING: AbbVie.