Common Rheumatic Disorders Research Articles

Methotrexate Intolerance in Juvenile Idiopathic Arthritis: Definition, Risks, and Management.

Juvenile idiopathic arthritis is the most common rheumatic disorder in childhood and adolescence posing a significant threat of short-term and long-term disability if left untreated. Methotrexate is a folic acid analog with various immunomodulatory properties. It has demonstrated significant efficacy for the treatment of juvenile idiopathic arthritis, often considered the preferred first-line disease-modifying anti-rheumatic drug given as monotherapy or in combination with biological drugs. Despite this, there is a considerable risk for treatment disruptions owing to the high prevalence of methotrexate intolerance, with symptoms such as nausea, stomach ache, vomiting, and behavioral symptoms. Many different risk factors for the intolerance have been proposed including gender, age, disease activity, treatment duration, dosing and administration, and genetic and psychological factors. As the studies have shown contradictory results, many questions are left unanswered. Therefore, a consensus regarding outcome measures and reporting is crucial. In this review, we describe the identification and assessment of methotrexate intolerance and evaluate potential risk factors, genetic associations as well as management strategies.

Prevalence of temporomandibular disorders in juvenile idiopathic arthritis evaluated with diagnostic criteria for temporomandibular disorders: A systematic review with meta-analysis.

Juvenile idiopathic arthritis (JIA) is a very common systemic inflammatory rheumatic disorder affecting the musculoskeletal system in children below 16 years of age. Joint inflammation and tissue destruction is the prime characteristic of the disease. Along with the systemic involvement in the long joints, several studies are mentioning the increased association of temporomandibular disorders (TMDs) in JIA. This current systematic review intends to find the prevalence rate of TMD in JIA-affected individuals as compared to healthy controls. We have searched in PubMed, Scopus and Ovid SP for articles published between the timeframe 1 January 1990 and 1 June 2023. All the searched articles were subjected to the Population, Exposure, Comparison, and Outcome model (PECO) based on which inclusion or exclusion is carried out. Participants (P) are children below 18 years of age, Exposure (E) is children or adolescents with a diagnosis of JIA, Comparator is age and gender-matched healthy controls who has no JIA or any systemic disorder, Outcome (O) is the prevalence of TMD. Only the studies that evaluated TMD using diagnostic criteria for evaluation of TMD (DC/TMD) were included in the analysis. We have set the exclusion to the following reasons- diagnostic sensitivity studies, case reports, and systematic reviews. The software Review Manager Version 5.4 (Cochrane Collaboration) was used to perform the pooled analysis. We measured the risk ratio (RR) between the two groups (JIA and no JIA) for the outcome TMD. The pooled total included subjects were 366 in this review with an established diagnosis of JIA as evaluated by DC/TMD. The overall effect of the pooled data suggests that there is a significant difference in the TMD prevalence in the JIA group when compared to the control, results suggest that TMD is more prevalent in the JIA group RR 3.86; 95% CI [2.59, 5.76]. Overall, based on the data we can suggest a positive relationship between JIA and TMD, hence presence of JIA can be a risk factor for the development of TMD. The sensitivity of DC/TMD is low when compared to magnetic resonance imaging.

E09 Juvenile idiopathic athritis: a desk review of the available standard treatment guidelines in East Africa

Abstract Background Juvenile Idiopathic Arthritis (JIA) is a common rheumatic disorder in children, with an estimated prevalence of 1 out of every 1000 children worldwide. In Tanzania, a retrospective review of pediatric patients with pediatric rheumatology conditions for seven years, reported JIA as the most prevalent condition. Timely initiation of therapy and availability of appropriate pharmacotherapy halts morbidity and mortality. Treatment guidelines for this condition is a key in guiding appropriate management. Aim This review was conducted to determine the availability of treatment guidelines for JIA in East Africa and compare them with the international guidelines. Methodology This was a desk review of available treatment guidelines for juvenile idiopathic arthritis in East Africa and as well international guidelines for comparison. The search was done on google, google scholar, Medline, HINARI and PubMed. The international guidelines were obtained from the respective webpages of the academic associations for rheumatology disorders. The search words entered in the data bases included ‘JIA treatment guidelines’, ‘Systemic arthritis treatment guidelines’, and ‘treatment guidelines for pediatric arthritis’. Each of the words was entered in the search engine with the names of the East African countries separately. Results There are no available standard guidelines for treatment of juvenile idiopathic arthritis in East Africa. However, available experts contextualize the international guidelines to attend local patients. This happens amidst a region with scarce resources. In a few available studies including ones conducted by A. Migowa et al. and M. Kamau et al. treatment includes use of NSAIDS for pain management, and corticosteroids for treatment bridging until Disease Modifying Anti-Rheumatic Drugs (DMARDS) become effective. Availability of biologics is not consistent in all the hospitals and their access is limited in third world countries (M. Kamau et al.). The reliable Disease Modifying Anti-Rheumatic Drugs of choice remain to be the convectional ones. The international guidelines exist for other regions including Europe (EULAR), America (ACR), and Asia pacific regions (APLAR). Conclusion There is a need to develop standard treatment guidelines in our settings in order to guide clinicians to best manage patients with JIA with the available treatment options in our setting.

A novel Anti-ROS osteoblast-specific delivery system for ankylosing spondylitis treatment via suppression of both inflammation and pathological new bone formation

Ankylosing spondylitis (AS) is a common rheumatic disorder distinguished by chronic inflammation and heterotopic ossification at local entheses sites. Currently available medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs) and TNF inhibitors, are limited by side effects, high costs and unclear inhibitory effects on heterotopic ossification. Herein, we developed manganese ferrite nanoparticles modified by the aptamer CH6 (CH6-MF NPs) that can efficiently scavenge ROS and actively deliver siRNA into hMSCs and osteoblasts in vivo for effective AS treatment. CH6-MF NPs loaded with BMP2 siRNA (CH6-MF-Si NPs) effectively suppressed abnormal osteogenic differentiation under inflammatory conditions in vitro. During their circulation and passive accumulation in inflamed joints in the Zap70mut mouse model, CH6-MF-Si NPs attenuated local inflammation and rescued heterotopic ossification in the entheses. Thus, CH6-MF NPs may be an effective inflammation reliever and osteoblast-specific delivery system, and CH6-MF-Si NPs have potential for the dual treatment of chronic inflammation and heterotopic ossification in AS.

Clinical Presentation and Treatment of Juvenile Idiopathic Arthritis Combined with Lung Disease: A Narrative Review.

Juvenile idiopathic Arthritis (JIA) is a common rheumatic disorder in children that can cause multiple systems to be affected simultaneously, leading to severe clinical symptoms and a high mortality rate in those with pulmonary involvement. Pleurisy is the most common manifestation of pulmonary involvement. At the same time, other conditions, such as pneumonia, interstitial lung disease, occlusive bronchiectasis, and alveolar protein deposition, have been increasingly reported in recent years. This review aims to provide an overview of the clinical manifestations of JIA lung damage and the current treatment options to assist in identifying and treating JIA lung involvement.

Comparison of the efficacy and safety of methotrexate alone or in combination with leflunomide in the treatment of juvenile idiopathic arthritis: a double-blind, placebo-controlled, randomized trial.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disorder in children. Although methotrexate (MTX) is the first line disease-modifying antirheumatic drug for JIA, many patients do not respond well or cannot tolerate MTX. The aim of this study was to compare the effect of combination therapy of MTX and leflunomide (LFN) with MTX in patients who do not respond to MTX. Eighteen patients (2-20 years old) with polyarticular, oligoarticular or extended oligoarticular subtypes of JIA who did not respond to conventional JIA therapy participated in this double-blind, placebo-controlled, randomized trial. The intervention group received LFN and MTX for 3 months while the control group received oral placebo and MTX at a similar dose to the intervention group. Response to treatment was assessed every 4 weeks using the American College of Rheumatology Pediatric criteria (ACRPed) scale. Clinical criteria, including number of active joints and restricted joints, physician and patient global assessment, Childhood Health Assessment Questionnaire (CHAQ38) score, and serum erythrocyte sedimentation ratelevel, did not differ significantly between groups at baseline and at the end of the 4th and 8th weeks of treatment. Only the CHAQ38 score was significantly higher in the intervention group at the end of the 12th week of treatment. Analysis of the effect of treatment on study parameters revealed that only the global patient assessment score differed significantly between groups (p = 0.003). The results of this study showed that combining LFN with MTX does not improve clinical outcomes of JIA and may increase side effects in patients who do not respond to MTX.

MicroRNAs-mediated regulation pathways in rheumatic diseases.

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are two common rheumatic disorders marked by persistent inflammatory joint disease. Patients with RA have osteodestructive symptoms, but those with AS have osteoproliferative manifestations. Ligaments, joints, tendons, bones, and muscles are all affected by rheumatic disorders. In recent years, many epigenetic factors contributing to the pathogenesis of rheumatoid disorders have been studied. MicroRNAs (miRNAs) are small, non-coding RNA molecules implicated as potential therapeutic targets or biomarkers in rheumatic diseases. MiRNAs play a critical role in the modulation of bone homeostasis and joint remodeling by controlling fibroblast-like synoviocytes (FLSs), chondrocytes, and osteocytes. Several miRNAs have been shown to be dysregulated in rheumatic diseases, including miR-10a, 16, 17, 18a, 19, 20a, 21, 27a, 29a, 34a, 103a, 125b, 132, 137, 143, 145, 146a, 155, 192, 203, 221, 222, 301a, 346, and 548a.The major molecular pathways governed by miRNAs in these cells are Wnt, bone-morphogenic protein (BMP), nuclear factor (NF)-κB, receptor activator of NF-κB (RANK)-RANK ligand (RANKL), and macrophage colony-stimulating factor (M-CSF) receptor pathway. This review aimed to provide an overview of the most important signaling pathways controlled by miRNAs in rheumatic diseases.

CHARACTERISATION OF SENESCENCE MARKERS IN VIVO IN AN AGE-RELATED OSTEOARTHRITIS MURINE MODEL AND IN VITRO IN AN IL-1β-INDUCED INFLAMMATORY OSTEOARTHRITIS MODEL AND AN ETOPOSIDE-INDUCED SENESCENCE MODEL

Purpose: Osteoarthritis (OA), the main osteoarticular disease is characterized by cartilage breakdown, synovial inflammation, osteophytes production, and subchondral bone remodeling. While OA is one of the most common rheumatic disorders, no efficient disease-modifying drugs still exist today. Ageing, a complex physiological process, consists of a gradual decline in certain functions, coordination, loss of homeostasis and physiological integrity, is a major risk factor for OA. Like in ageing, an accumulation of senescent cells is observed within the OA joint, and elimination of senescent cells has been shown to reduce pain and increase cartilage development in murine post-traumatic OA.

Gender influence on clinical manifestations, depressive symptoms and brain-derived neurotrophic factor (BDNF) serum levels in patients affected by fibromyalgia

IntroductionObjectivesFibromyalgia (FM) is a common rheumatic disorder characterized by chronic, widespread pain associated with several not painful symptoms. The contribution of gender to the manifestation of the disease may influence the higher prevalence of FM among women. In spite of this, how patients’ gender influences the clinical manifestation of FM is still not well understood. The frequent association with neuropsychiatric symptoms raised the attention on the role of neurotrophins, including the brain-derived neurotrophic factor (BDNF) as potential biomarkers of the condition. Aims of the study were to evaluate the influence of gender on clinical manifestations and to investigate BDNF serum levels as a potential biomarker of FM.MethodsWe consecutively enrolled 201 adult patients of both sexes diagnosed with FM. For each patient, we collected clinical and clinimetric data and, in a subgroup of 40 patients, we measured serum BDNF levels. BDNF levels have been measured also in 40 matched healthy controls (HC).ResultsSeveral symptoms were significantly higher in women compared with men, including pain, fatigue, memory problems, tenderness, balance problems and sensitivity to environmental stimuli. On the contrary, men reported a significant higher frequency of coexisting depressive symptoms. BDNF levels were significantly lower in FM patients compared with HC, discriminating with good accuracy the condition.ConclusionGender influences FM clinical manifestations, with a higher prevalence of pain, fatigue and other common FM symptoms among women while higher frequency of neuropsychiatric symptoms among men. BDNF offers promises as a potential biomarker of the disease.Key Points• Gender-related differences in the clinical manifestations of FM may contribute to the higher prevalence of FM among females. Indeed, women show higher levels of pain and symptoms traditionally associated to FM, which are evaluated to establish the diagnosis according to the clinical criteria.• The new insights into the pathogenesis of the disease raised the attention on the role of brain mediators in FM. Among these, BNDF shows potential as a diagnostic biomarker.

O05 A case of cancer mimicking inflammatory arthritis

Abstract Case report - Introduction Rheumatic disease occurring as a paraneoplastic manifestation such as dermatomyositis is well recognised, whilst the symptoms of cancer may frequently mimic the presentations of common rheumatic disorders. It is essential to recognise these differential diagnoses to avoid delay in the detection of malignancy. We present an unusual case of rheumatoid arthritis where, conversely, the diagnosis of inflammatory arthritis was delayed due to the attribution of musculoskeletal symptoms to existing malignancy undergoing treatment. This case highlights the importance of careful history and examination. Cancer and inflammatory disorders may co-exist and delayed diagnosis of either condition can result in increased morbidity. Case report - Case description A 65-year-old male presented to Ear, Nose and Throat (ENT) clinic with a facial lump in association with swelling in his throat, tongue and neck associated with a decrease in appetite and weight loss. He reported an active lifestyle, including mountain climbing until a month prior. He was a non-smoker with alcohol intake of less than 10units/week. Other medical history included osteoarthritis of his left knee which did not limit function. Imaging of the head and neck confirmed a mass in the oropharynx, tonsils, and tongue muscles. Subsequent biopsy revealed moderate to poorly differentiated squamous cell carcinoma (SCC) of the left tonsil. 11 months prior to this presentation, he had developed pain and swelling involving knees, shoulders, and small joints of hands. His mobility became progressively impaired eventually requiring a wheelchair for any outdoor excursion. The systemic and musculoskeletal symptoms were attributed to a paraneoplastic manifestation of his malignant process. A rheumatology opinion was eventually requested in view of the persistence of joint symptoms despite effective cancer treatment with radical radiotherapy. He described early morning stiffness lasting more than 3 hours. Synovitis was evident at his hands, wrists and knees, whilst shoulder movement was restricted, resulting in a high disease activity score (DAS) of 7.44. Blood workup showed normal rheumatoid factor and cyclic citrullinated peptide (CCP). Acute phase markers were elevated with ESR 99 mm/hr, CRP 79 mg/l and ferritin 1194 ng/ml. Ultrasound (US) hands confirmed widespread active synovitis involving bilateral wrist and metacarpophalangeal joints. X-rays showed only degenerative changes. A diagnosis of seronegative inflammatory arthritis was established, and he was initiated on hydroxychloroquine with reducing regime of prednisolone. Methotrexate (MTX) was briefly deferred pending oncology advice. Following initiation of MTX he improved dramatically, returning to normal mobility, and steroids were successfully tapered off. Case report - Discussion Our patient had symptoms of inflammatory arthritis prior to identification of a SCC with local spread; however, his systemic and musculoskeletal features were initially regarded as paraneoplastic. Paraneoplastic arthritides encompass the musculoskeletal manifestations of malignancy. This includes polyarthritis, inflammatory myopathies, hypertrophic osteoarthropathy and palmar fasciitis. Symptoms may precede or occur concurrently with cancer presentations and often respond to treatment of the underlying cancer. Persistence of musculoskeletal symptoms may be a clue to co-existence of a rheumatic diagnosis. Reassessment of history and examination can guide physicians to a concurrent second diagnosis when clinical progress is not as expected. Our case also highlights the question of safe use of immunosuppressive drugs in rheumatic patients with cancer and whether they may promote or induce malignant disease. Literature is challenging to assess as many systemic inflammatory disorders, including RA, have an established increased risk of certain cancers, including lymphoproliferative disease. He was managed by prednisolone and hydroxychloroquine, followed rapidly by MTX, leading to dramatic symptomatic improvement. Low-dose MTX (25—30mg weekly) is considered first-line treatment in RA. Of the commonly used anti-rheumatic therapies it has the least evidence to suggest a potential increased malignancy risk. Other anti -rheumatic drugs such as Tumour Necrosis Factor (TNF) inhibitors also have a favourable risk profile regarding cancer development. Most observational studies evaluating the use of biologic therapy in RA patients with previous solid tumours do not show an increased risk of recurrence. Coordination of care with the patient and their oncologist is essential in the management of cases of individuals with rheumatic disease and concomitant cancer. Case report - Key learning points

Biological Therapy in Primary Sjögren's Syndrome: Effect on Salivary Gland Function and Inflammation.

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease. It is the second most common rheumatic autoimmune disorder, affecting 0.7% of European Americans and up to 1% of people globally. pSS is characterized by the impaired secretory function of exocrine glands, including salivary and lachrymal glands. A lymphocytic infiltration of these organs leads to the common and debilitating symptoms of oral and ocular dryness, majorly affecting the quality of life of these patients. Currently, no disease-modifying drug has been approved for the treatment of pSS, with therapies largely aimed at relieving symptoms of dry mouth and dry eyes. In particular, management of oral dryness still represents a major unmet clinical need in pSS and a significant burden for patients with this condition. Recently, several randomized clinical trials in pSS with biological therapies targeting specific mechanistic pathways implicated in the disease pathogenesis, including B-cell hyperactivity, T-cell co-stimulation and the aberrant role of cytokines, have been completed with mixed results. In this review, we summarize evidence from recent clinical trials investigating biological therapy in pSS, specifically highlighting efficacy, or lack thereof, in modulating local inflammation and improving salivary gland function.

MR Imaging of Rheumatic Diseases Affecting the Pediatric Population.

This article reviews the application of magnetic resonance imaging (MRI) to pediatric rheumatic diseases. MRI can detect early manifestations of arthritis, evaluate the extent of disease, and monitor disease activity and response to treatment.Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disorder, representing a diverse group of related diseases that share a definition of joint inflammation of unknown origin with onset before 16 years of age and lasting > 6 weeks. JIA may lead to significant functional impairment and is increasingly imaged with MRI to assess for active inflammation as a target for therapy. This is particularly true for juvenile spondyloarthritis that includes multiple subgroups of JIA and primarily involves the spine and sacroiliac joints.Other less common pediatric rheumatic diseases considered here are chronic recurrent multifocal osteomyelitis and collagen vascular diseases including polymyositis, dermatomyositis, scleroderma, and juvenile systemic lupus erythematosus.

NMR-based clinical metabolomics revealed distinctive serum metabolic profiles in patients with spondyloarthritis.

Spondyloarthritis (SpA) is a common rheumatic disorder of the young, marred by delay in diagnosis, and paucity of biomarkers of disease activity. The present study aimed to explore the potential of serum metabolic profiling of patients with SpA to identify biomarker for the diagnosis and assessment of disease activity. The serum metabolic profiles of 81 patients with SpA were compared with that of 86 healthy controls (HCs) using nuclear magnetic resonance (NMR)-based metabolomics approach. Seventeen patients were followed up after 3 months of standard treatment, and paired sera were analyzed for effects of therapy. Comparisons were done using the multivariate partial least squares discriminant analysis (PLS-DA), and the discriminatory metabolic entities were identified based on variable importance in projection (VIP) statistics and further evaluated for statistical significance (p value < 0.05). We found that the serum metabolic profiles differed significantly in SpA as compared with HCs. Compared with HC, the SpA patients were characterized by increased serum levels of amino acids, acetate, choline, N-acetyl glycoproteins, Nα-acetyl lysine, creatine/creatinine, and so forth and decreased levels of low-/very low-density lipoproteins and polyunsaturated lipids. PLS-DA analysis also revealed metabolic differences between axial and peripheral SpA patients. Further metabolite profiles were found to differ with disease activity and treatment in responding patients. The results presented in this study demonstrate the potential of serum metabolic profiling of axial SpA as a useful tool for diagnosis, prediction of peripheral disease, assessment of disease activity, and treatment response.

Endothelial Dysfunction in Patients with Rheumatoid Arthritis: the Role of Hypertension.

To review the data on the role of endothelial dysfunction and the impact of hypertension as a potent mediator of cardiovascular disease in patients with rheumatoid arthritis (RA). RA represents the most common autoimmune rheumatic disorder and is characterized by chronic systemic inflammation predisposing to cardiovascular complications. Cardiovascular mortality is increased among patients with RA and represents the leading cause of death. Although the exact prevalence is debated, hypertension is increased in RA. Hypertension acts synergistically with chronic inflammation and accounts, at least partially, for the increased cardiovascular morbidity in this group of patients. Endothelial dysfunction is considered a primary process in the pathogenesis of hypertension and cardiovascular diseases and contributes significantly to the development and progression of the associated micro- and macrovascular complications. Even though several studies in patients with RA have shown the presence of endothelial dysfunction with traditional methods, novel biochemical and vascular methods for the evaluation of endothelial dysfunction have been scarcely applied. In addition, it remains unclear whether and to which extent endothelial dysfunction in RA is present regardless of concomitant hypertension, even in well-controlled patients. Hypertension, endothelial dysfunction, and chronic systemic inflammation appear as a mutually reinforcing triad aggravating cardiovascular risk in patients with RA. Detection of endothelial dysfunction in patients with RA in the early stages further aiming at the development of novel therapeutic targets might contribute to prevention of cardiovascular complications and remains under investigation.

Similar Transition Processes in Synovial Fibroblasts from Rheumatoid Arthritis and Osteoarthritis: A Single-Cell Study.

Rheumatoid arthritis (RA) and osteoarthritis (OA) are common rheumatic disorders that primarily involve joints. The inflammation of the synovium can be observed in both of the two diseases. Synovial fibroblasts (SFs) play an important role in the inflammatory process of the synovium. The functional states of synovial fibroblasts are heterogeneous, and the detailed transition process of their functional states is still unclear. By using transcriptomic data of SFs at a single-cell level, we found a similar transition process for SFs in RA and OA. We also identified the potential regulatory effects of the WNT signaling pathway, the TGF-β signaling pathway, the FcεRI signaling pathway, and the ERBB signaling pathway on modifying the SFs' functional state. These findings indicate potentially overlapped pathogenic mechanisms in these two diseases, which may help uncover new therapeutic targets to ameliorate disease progression.

Back Pain and Common Musculoskeletal Problems

Knowledge of the common nonarticular regional rheumatic disorders is important because of their high prevalence in primary care practice, the dependence on clinical findings for diagnosis, and the high cost that can result from unnecessary laboratory evaluations. The ability to recognize important patterns of pain and associated physical signs is essential to making a correct diagnosis; in most cases, radiographic and laboratory studies are not needed. This review covers the common causes of pain in the neck, back, shoulder, chest wall, elbow, hand and wrist, hip girdle, knee and lower leg, and ankle and foot. This review contains 5 figures, 11 tables, and 96 references. Key words Acute back pain, Chronic back pain, Lumbar stenosis, Shoulder pain, Chest wall pain, Elbow pain, Hand and wrist pain, Carpal Tunnel Syndrome, Hip girdle pain, Knee and lower leg pain, Ankle and foot pain

Development and characterization of a humanized mouse model of osteoarthritis

Purpose: Normal 0 21 false false false FR X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tableau Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman",serif; border:none;} <Osteoarthritis (OA) is mainly characterized by cartilage breakdown and synovial inflammation. While OA is one of the most common rheumatic disorders, no efficient disease-modifying drugs still exist today. Mesenchymal stem cells (MSC) have generated significant medical considerations since they exhibit tissue-regenerative properties through the secretion of bioactive factors. Phase I-II clinical trials have shown that intra-articular (IA) injection of MSC is well-tolerated and exhibited promising clinical results. However, MSC display a poor survival and engraftment rate in vivo. Using encapsulating systems could protect MSC and maintain their bioactivity after intra-articular injection. Considering the pivotal role of inflammation and immune system in OA and with regards to the differences between MSC-mediated immunomodulation in human and mice (12), the development of sophisticated animal models that could more closely mimic the human immune system, could be instrumental. Amongst these models, immunologically humanized mice may represent a preclinical bridge between in vitro studies and the in vivo evaluation of human stem cells in OA. Our objective is therefore to develop an experimental model of osteoarthritis by destabilizing the medial meniscus (DMM) in humanized mice.> Methods: Normal 0 21 false false false FR X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tableau Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman",serif; border:none;} <4 weeks-old NOD/LtSz-scid IL2Rγnull (NSG) mice were humanized as follow. After irradiation (1,5Gy), 5.106 CD34+ human hematopoietic stem cells were injected intravenously. 120 days after the humanization procedure, the level of human immune cells CD45+ (leukocytes), CD3+ (T lymphocytes), CD19+ (B lymphocytes), CD56+ (NK cells) and CD14+ (macrophages) were evaluated by flow cytometry. Humanized NSG mice then had undergone a DMM or a SHAM surgery. 6 and 12 weeks after OA induction the development of osteoarthritis was assessed histologically by safranin-o staining, OA score and histomorphometric analysis of the knees. In addition, to evidence the presence of human immune cells in the joint, Immunohistochemicals stainings for human CD45+, CD3+, CD19+ et CD56+ and CD14+ cells have also been performed.> Results: Normal 0 21 false false false FR X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tableau Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman",serif; border:none;} <Our results showed that 120 days after the humanization procedure, NSG mice exhibit engraftment level (hCD45+) from 10% to 75 % and the presence of human T and B lymphocytes as well as macrophages and NK cells in blood and spleen. Our histological results show that the DMM procedure induce a significant increase in OA score at 12 weeks compared to sham mice. Our histomorphometric results also evidence a significant increase in bone volume of the anterior medial meniscus. However, no significant differences have been observed between DMM and Sham mice on the OA score at 6 weeks and on the subchondral bone morphometry at 6 and 12 weeks’ post-surgery. Immunohistochemical analyses have however revealed the presence of human B lymphocytes and macrophages in the subchondral bone marrow but not in the synovial membrane at 6 and 12 weeks post-surgery.> Conclusions: Normal 0 21 false false false FR X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Tableau Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman",serif; border:none;} <Finally, using 2 methods of analysis (histology and histomorphometry), we have demonstrated that humanized NSG mice could develop post-traumatic OA after a DMM surgery. The presence of human immune cell in the spleen and subchondral bone marrow confirms the success of the hematopoietic transplant. However, we failed to detect any immune cells in the synovial membrane or articular cartilage although human immune cells were observed near the joint in the subchondral bone marrow. The search for these immune cells in the synovial membrane would be more appropriate during the inflammatory burst, meaning within the first 2 weeks following the DMM surgery. Our results therefore evidence the feasibility to induce OA by DMM in humanized mice. This model could constitute a useful tool to study the therapeutic efficacy of encapsulated human mesenchymal stem cells.>

DEMOGRAPHIC AND ETIOLOGIC INVESTIGATION OF GOUT ARTHRITIS CASES IN THE KARS REGION, A COMPARATIVE RETROSPECTIVE STUDY

Introduction: Gout arthritis is a very common rheumatic disorder. The hyperuricemia develops due to increased serum uric acid synthesis and/or decreased renal excretion.&#x0D; Material and Method: This study was conducted after permission was obtained from the Kafkas University Ethics Committee (KAU-26-06-2018-09). We included patients who presented to the Kars Harakani State Hospital and the Kafkas University Faculty of Medicine Orthopedics and Traumatology outpatient department between May 2012 and December 2018 and were diagnosed with gout arthritis into the study. The patients were divided into two groups as Group I (n:87) consisting of patients who received Allopurinol (Xanthine Oxidase Inhibitor) at a dose of 100 mg 1x1 po for 4 weeks together with a purine-poor diet (provided as a list) and Group II (n:77) consisting of patients recommended abundant water consumption (2 lt/day), decreased tea consumption, increased milk and dairy products consumption and a purine-poor diet (given as a list) without the administration of any drugs. Both groups were called 4 weeks later for clinical follow-up and they underwent a physical examination and laboratory evaluations at the outpatient department. Treatment protocols were evaluated comparatively according to the uric acid levels and physical examination findings.&#x0D; RESULTS: Group I received a xanthine oxidase inhibitor + purine-poor diet and consisted of 5 female and 19 male patients aged 18-60 years and 17 female and 46 male patients aged 60 and over. Group II received optimal Hydration + milk and dairy products + purine-poor diet and consisted of 24 females and 53 males aged 60 and over without any patients in the 18-60 years age group. Pretreatment uric acid levels and posttreatment 4th week uric acid levels were compared.&#x0D; CONCLUSION: In addition to gout arthritis treatment with drugs, it is possible to treat these patients without giving any drugs by increasing the consumption of milk and dairy products together with optimal hydration.&#x0D; Key Words: Gout arthritis, Xanthine oxidase inhibitor, optimal hydration, Milk

Back Pain and Common Musculoskeletal Problems

Knowledge of the common nonarticular regional rheumatic disorders is important because of their high prevalence in primary care practice, the dependence on clinical findings for diagnosis, and the high cost that can result from unnecessary laboratory evaluations. The ability to recognize important patterns of pain and associated physical signs is essential to making a correct diagnosis; in most cases, radiographic and laboratory studies are not needed. This review covers the common causes of pain in the neck, back, shoulder, chest wall, elbow, hand and wrist, hip girdle, knee and lower leg, and ankle and foot. This review contains 5 figures, 11 tables, and 96 references. Key words Acute back pain, Chronic back pain, Lumbar stenosis, Shoulder pain, Chest wall pain, Elbow pain, Hand and wrist pain, Carpal Tunnel Syndrome, Hip girdle pain, Knee and lower leg pain, Ankle and foot pain

Back Pain and Common Musculoskeletal Problems

Knowledge of the common nonarticular regional rheumatic disorders is important because of their high prevalence in primary care practice, the dependence on clinical findings for diagnosis, and the high cost that can result from unnecessary laboratory evaluations. The ability to recognize important patterns of pain and associated physical signs is essential to making a correct diagnosis; in most cases, radiographic and laboratory studies are not needed. This review covers the common causes of pain in the neck, back, shoulder, chest wall, elbow, hand and wrist, hip girdle, knee and lower leg, and ankle and foot. This review contains 5 figures, 11 tables, and 96 references. Key words Acute back pain, Chronic back pain, Lumbar stenosis, Shoulder pain, Chest wall pain, Elbow pain, Hand and wrist pain, Carpal Tunnel Syndrome, Hip girdle pain, Knee and lower leg pain, Ankle and foot pain