No Correlation between Anti-drug Antibodies and Therapeutic Response in Tunisian Patients with Chronic Inflammatory Diseases Treated by TNF Blockers.

INTRODUCTION: Tumor necrosis factor alpha (TNF alpha) blockers such as infliximab (IFX) and adalimumab (ADA) had significantly changed the course of inflammatory diseases such as rheumatoid arthritis (RA), spondyloarthritis (SpA) and Crohn's disease (CD). However, about 30% of patients do not respond to these treatments. This lack of response may be due to the formation of antibodies against these drugs (anti-drug antibodies: ADAbs). The aim of this study was to determine the prevalence of ADAbs against IFX and ADA, and the trough serum concentration of IFX and ADA in RA, SpA or CD patients and to assess their impact on the therapeutic response. METHODS: A cross sectional, multi-centric study was conducted, including patients with RA, SpA or CD treated with IFX or ADA as a first biotherapy for at least 6 months. ADAbs and trough levels were measured by an Enzyme Linked Immunosorbent assay (ELISA). RESULTS: 197 patients were included (57 RA, 73 SpA and 67 CD). ADAbs were positive in 40% of cases for IFX and 25% for ADA. They were positive in 40% of SpA, 35% of RA, and 21% of CD. The presence of ADAbs was inversely correlated to the trough levels of IFX and ADA during RA (p = 0.01 and p < 0.0001), SpA (p < 0.01 and p < 0.0001) and CD (p = 0.001 and p = 0.04). For all pathologies, the presence of ADAbs was not correlated with disease activity. Concomitant methotrexate significantly reduced immunogenicity. CONCLUSION: In our study, the presence of ADAb and low trough levels seem to not affect the therapeutic response in patients on TNF alpha antagonists. Other tracks more than immunogenicity should be investigated to explain the loss of response to these biotherapies.

Spinal Tuberculosis: Features and Early Predictive Factors of Poor Outcomes.

Introduction: Tuberculosis is still endemic in Tunisia. Among musculoskeletal involvement, spinal tuberculosis (STB) or «Pott's Disease¼ is the most common and can lead to serious neurological complications. The purpose of our study was to focus on STB features (clinical, biological, and radiological) and to identify factors associated with early unfavorable outcomes. Methods: This was a monocentric retrospective study, over a period of 20 years (2000-2020). Only patients treated appropriately were included. Patients' informations were noted. We defined the favorable outcome criterion as weight gain, apyrexia, improvement of the general state, relief of pain, improvement in the classic inflammatory markers (CRP), and absence of vertebral deformities, neurological impairment, or sepsis. The outcome was considered unfavorable otherwise. Results: Our study involved 52 patients. Their average age was 55.21 years±17.79. The average symptom duration was 8.9 months±6.54. Spinal pain was the most common functional sign (90.4%) often inflammatory. Physical signs were dominated by segmental spinal stiffness (71.2%). Spinal magnetic resonance imaging was performed in 38 patients. The disco-vertebral biopsy puncture confirmed the diagnosis in 15 cases. All patients received anti-tuberculosis treatments with an average duration of 10.02±1.97months. The outcome at one month of follow-up was favorable in 32 cases. Poor prognosis factors were normochromic normocytic anaemia (p=0.018), initial lymphocytosis (p=0.048), and fever (p=0.01). However, vertebral fracture at standard X-ray was predictive of favorable outcome (p=0.001). Conclusion: STB is a frequent condition that needs to be treated rapidly. Poor prognosis factors were identified in this study such as normocytic normochromic anemia, initial lymphocytosis, and fever at baseline.

Focal Segmental Glomerulosclerosis and Hyalinosis in a Patient with Spondyloarthritis: A Rare Renal Involvement Case Report.

Background: During its course, spondyloarthritis (SpA) may be associated with extra-articular manifestations affecting several organs. Renal involvement is one of the most common extra-articular manifestations and is dominated by secondary amyloidosis (AA), immunoglobulin A (IgA) nephropathy, and urolithiasis. Other nephropathies such as Focal segmental glomerulosclerosis and hyalinosis (FSGS) are less common and are limited to few case reports. Case: We report the case of a patient followed for axial SpA, who consulted, after being lost to follow-up for 3 years, for elevated blood pressure and edema of both lower limbs associated with an hydrocele and bilateral pleural effusion. Biological examinations showed hypoproteinemia, hypoalbuminemia, and proteinuria. In this context of nephrotic syndrome, the diagnosis of FSGS was confirmed by renal biopsy. Furthermore, the etiological investigation ruled out the causes of secondary FSGS. Conclusion: Renal involvement is a sign of severity in SpA. Its detection and management should be part of the overall management of SpA.

Green Fabrication of Sustainable Porous Chitosan/Kaolin Composite Membranes Using Polyethylene Glycol as a Porogen: Membrane Morphology and Properties.

One of the major challenges in membrane manufacturing today is to reduce the environmental footprint by promoting biobased raw materials and limiting the use of toxic solvents. In this context, environmentally friendly chitosan/kaolin composite membranes, prepared using phase separation in water induced by a pH gradient, have been developed. Polyethylene glycol (PEG) with a molar mass ranging from 400 to 10,000 g·mol-1 was used as a pore forming agent. The addition of PEG to the dope solution strongly modified the morphology and properties of the formed membranes. These results indicated that PEG migration induced the formation of a network of channels promoting the penetration of the non-solvent during the phase separation process, resulting in an increase in porosity and the formation of a finger-like structure surmounted by a denser structure of interconnected pores of 50-70 nm in diameter. The hydrophilicity of the membrane surface increased likely related to PEG trapping in the composite matrix. Both phenomena were more marked as the PEG polymer chain was longer, resulting in a threefold improvement in filtration properties.

Influencing Factors in Tunisian Rheumatoid Arthritis Patients' Quality of Life: Burden and Solutions.

BACKGROUND: Rheumatoid Arthritis (RA) is a disease with a heavy functional, psychological, and socioeconomic impact. The management of Quality of Life (QoL) as a therapeutic objective is a fairly recent notion, especially in Tunisia. We aimed to evaluate QoL in RA patients and to identify its affecting factors. METHODS: This was a cross-sectional study in a Tunisian rheumatology center. To assess QoL, we used the Short Form Health Survey (SF-36) and the Arthritis Impact Measurement Scales Short Form (AIMS2-SF). Health Assessment Questionnaire Disability Index (HAQ), the Hospital Anxiety and Depression Scale (HAD) for psychological disorders, Visual Analog Scale for Pain (VAS Pain), and for fatigue (VAS Fatigue) were also used. Disease activity was assessed by the Disease Activity Score (DAS28 CRP). RESULTS: We enrolled 120 established RA, the mean age of our patients was 56.9 ± 11.4 years, with a predominance of women (83.3%). The mean disease duration was 10.97 ± 7.7 years. According to the HAD scale, 27% of our patients presented anxiety, and 26.7% had depressive disorders. There was significantly impaired QoL in patients with low educational level, dependent financial situation, long disease duration, high disease activity, high pain and fatigue levels, poor therapeutic education, functional disability, and psychological disorders (p < 0.001). A strong negative correlation was detected between inflammatory markers, structural damage, and the scores of QoL. Patients under biologics scored significantly higher in the SF36 mental health domain (p < 0.001). CONCLUSION: QoL is significantly poor in Tunisian RA. These patients should be managed using a multidisciplinary approach involving the patients themselves.

Foot Functional Disability in Rheumatoid Arthritis: The Involvement of Body Mass Index.

INTRODUCTION: Overweight and obesity are common in patients with Rheumatoid Arthritis (RA), with a probable impact on bearing foot joints. AIM: Our study aimed to explore the impact of Body Mass Index (BMI) on foot health parameters in RA patients. METHODS: It was a cross-sectional study. Domains of foot health explored were: foot pain (Numeric Rating Scale), foot-related activity limitations (Foot Function Index (FFI), and WOMAC scale), foot synovitis, foot deformity (Platto Score (PS)), radiological joint damage and footwear problems. RESULTS: Fifty RA were included, 82% were female. The mean age was 45.68 ± 10.3 years. The mean DAS28-CRP was 3.25 ± 0.98. Sixty-six percent were overweight or obese, with a mean BMI of 29 Kg/m2 ± 5.74. The average foot pain intensity while walking was 6 ± 1.75. The mean swollen foot joint was 2.2 ± 1.55. The average foot structural index was 7.8 ± 2.73. The mean FFI Disability score was 32 ± 14.2 and WOMAC score was 33.8 ± 13.98. Half of our patients had footwear problems predominantly because of claw toe (40%). High BMI was significantly correlated with foot pain and foot-related activity limitations. It was also correlated with foot deformities assessed with PS (B=4.78; CI(3.87-5.68); p = 0.02), foot synovitis (OR=4.66, CI(2.61-8.32); p < 0.001) and problems with footwear (OR= 0.32; CI(0.18-0.56); p = 0.05). However, it was significantly associated with less radiological joint damage (CI(-0.7-1.1); p = 0.01) and lower foot sharp score (B = -13.9; CI(-0.34-0.01); P = 0.06). CONCLUSION: Despite our findings of a possible protective effect of obesity on structural damage, obesity is still an important cause of increased pain, functional disability, and impaired QoL in RA patients.

Low Back Pain Among Students of Medical University of Tunis.

OBJECTIVE: Low Back Pain (LBP) is the most common musculoskeletal disorder among working adults. It is one of the most prevalent complaints among students. Medical students are among those who are most exposed to this condition; due to stress, numerous hours of studying, and the sedentary lifestyle. Our study aimed to determine the prevalence and associated factors of LBP among the students of Tunis Faculty of Medicine and to assess its impact on student life. METHODS: This cross-sectional study was carried out on the Tunis Faculty of Medicine students. Data were collected through an online self-administered questionnaire. Sociodemographic, personal, and lifestyle characteristics were collected. LBP was assessed using the Nordic Musculoskeletal Health Questionnaire and Its impact using the Oswestry Disability Index (ODI). RESULTS: One hundred and forty-eight students were included. The mean age was 22.9 ± 2.3 years (19.64-38.21). The sex ratio was 0.29. According to the Nordic questionnaire, the point, annual and lifetime prevalence of LBP were 37.8%, 80.4%, and 90.5%, respectively. The mean ODI score was 10.32 ± 8.48 % (0-32). The ODI score was minimal in 87.3% and moderated in 12.7% of cases. The associated factors with LBP were: young age (p = 0.015), spending more than 4 hours in a sitting position (p = 0.059), second cycle of medical studies (p = 0.006), low screen projection in the amphitheater (p = 0.029) and poor layout of the amphitheatres (p = 0.000). The feeling of depression was significantly higher among LBP students (p = 0.018). In the multivariate analysis, the factors that remained statistically significant were the second cycle of medical studies (OR= 3.41), feeling of depression (OR = 3.7), and the belief in the responsibility for the poor layout of the amphitheaters in the genesis or maintenance of LBP (OR = 7.66). CONCLUSION: LBP in medical students is multifactorial across both personal and college-life domains.

Ultrasonography Enthesitis and Synovitis Screening in Psoriatic Patients: A Case Control Study.

Background: The clinical screening of enthesitis and synovitis in patients with psoriasis lacks specificity and sensitivity during the preclinical phase. Aims: to assess US subclinical synovitis and enthesitis in psoriatic patients compared with healthy controls. Methods: A cross-sectional study on 40 psoriatic patients and 40 healthy sex- and age-matched controls. US examination of 18 joints was performed along with 22 entheseal sites on the upper and lower limbs. US subscores were established according to the US abnormalities: inflammatory score (tendon thickening, hypoechogenicity, bursitis, Doppler signal), damage score (calcification, enthesophytes, bone erosion) and total score (the sum of inflammatory and damage scores). Results: US synovitis were more frequent in psoriatic patients (0.68%) than in controls (0.29%), but the difference was not significant. Patients with psoriasis had more US enthesitis (92,5%) compared to controls (40%)(p<0.001). The total number of enthesitis was higher in the psoriatic group (20.90%) compared to controls (4,78%)(p<0.001). There were more US abnormalities in the psoriatic group compared to controls for calcaneal tendon enthesis(p<0.001), distal patellar tendon enthesis(p<0.001) and deep flexor tendons of the finger enthesis(p<0.001). Compared to controls, psoriatic patients had a significantly higher inflammatory score (Mean±SD) (2.85±3.34 versus 0.58±1.17), damage score (3±2.57 versus 0.60±1.41), and total score (5.85±5.20 versus 1.18±2.07) (p < 0.001 each). Patients with scalp psoriasis had more US enthesitis (p=0.020). Conclusion: Our results indicate that US enthesitis and synovitis are more frequent in patients with psoriasis. Prospective studies with larger sample size are needed to define the contribution of US in predicting the clinical onset of PsA.

The synovial fluid fibroblast-like synoviocyte: A long-neglected piece in the puzzle of rheumatoid arthritis pathogenesis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease during which fibroblast-like synoviocytes (FLS) contribute to both joint inflammation and destruction. FLS represent the core component of the synovial membrane. Following inflammation of this membrane, an effusion of cell-rich synovial fluid (SF) fills the joint cavity. Unlikely, SF has been shown to contain fibroblasts with some shared phenotypic traits with the synovial membrane FLS. These cells are called SF-FLS and their origin is still unclear. They are either brought into the synovium via migration through blood vessels, or they could originate within the synovium and exist in projections of the synovial membrane. SF-FLS function and phenotype are poorly documented compared to recently well-characterized synovial membrane FLS subsets. Furthermore, no study has yet reported a SF-FLS single-cell profiling analysis. This review will discuss the origin and cellular characteristics of SF-FLS in patients with RA. In addition, recent advances on the involvement of SF-FLS in the pathogenesis of RA will be summarized. Current knowledge on possible relationships between SF-FLS and other types of fibroblasts, including synovial membrane FLS, circulating fibrocytes, and pre- inflammatory mesenchymal (PRIME) cells will also be addressed. Finally, recent therapeutic strategies employed to specifically target SF-FLS in RA will be discussed.

Unknown Extra-Articular Manifestation of Spondyloarthritis: What About Retroperitoneal Fibrosis? A Case Based Literature Review.

INTRODUCTION: Retroperitoneal fibrosis (RPF) is a rare disease characterized by fibroinflammatory tissue proliferation in the retroperitoneum. It results in a chronic inflammatory and fibrosis condition, possibly leading to compression of the retroperitoneal structures, especially to encasement of the ureters and the inferior vena cava. It may have an idiopathic or a secondary origin. Spondyloarthritis (SpA) is one of the rare conditions described among the secondary forms. CASE PRESENTATION: Herein, we report a new case of RPF in a patient with AS presented with acute abdominal pain radiating to the lumbar region and the left testicle. On clinical examination, we found a mild stiffness of the lumbar spine and a decrease in chest expansion. Sacroiliac joint pain was also found. The rest of the physical examination was normal. Laboratory tests showed inflammation with increased C-reactive protein (130 mg/l) and creatinine (112 micromol/l) levels. The computed tomography scan revealed a soft tissue density mass located around the sub-renal aorta. Diagnosis of idiopathic RPF associated with AS was retained. The patient was treated with a daily dosage of 1 mg/kg of oral glucocorticoid with a good outcome. CONCLUSION: RPF is a rare condition that can be either idiopathic or secondary. Its association with spondyloarthritis, mainly in its ankylosing spondylitis form, seems to be more than anectodal. Treatment may involve medical therapy and/or surgical management. KEY MESSAGE: In the presence of back pain, fatigue, weight loss, and low grade fever in spondyloarthritis patients, physicians should screen for retroperitoneal fibrosis as it could be a possible cause.

The effects of autoimmune rheumatic-related diseases on male reproductive health: A systematic review.

Autoimmune rheumatic-related diseases (ARRDs) have physical and psychological impact on patients, including their sexual life. While many studies have investigated fertility problems in females, data on males-related fertility are scarce, which explains the lack of guidance. The main objective of this systematic review was to evaluate the reproductive health in males with ARRDs. This systematic review followed the preferred reporting items for systematic reviews guidelines. Original articles from Pubmed and Scopus, published until September 16, 2021, and tackling the effects of ARRDs and/or ARRDs treatments on male fertility and/or pregnancy outcomes, were included. A total of twenty-five studies met the inclusion criteria. They were published between 1981 and 2018. The studied ARRDs were spondyloarthritis (n = 9), systematic lupus erythematosus (SLE, n = 6), Behcet disease (BD, n = 5), rheumatoid arthritis (RA, n = 5), antiphospholipid syndrome (n = 1), and dermatomyositis (n = 1). The most reported effects of ARRDs on fertility are i) high levels of reproductive hormones, mainly in RA and SLE; ii) impaired semen quality in SLE, spondyloarthritis, and BD; and iii) higher rate of varicocele in BD and spondyloarthritis. Regarding the treatments effects, i) conventional synthetic disease-modifying anti-rheumatic drugs (e.g.; methotrexate and salazopyrine) increase testosterone level, ii) cyclophosphamide impairs fertility, iii) anti-tumor necrosis factor agents are associated with improvement in semen quality, and iv) no increased number of miscarriages or congenital abnormalities in children fathered by BD was reported. To conclude, both ARRDs and their treatments alter fertility in males with ARRDs. In practice, in addition to the conventional semen analysis, screening for infertility seems legitimate in males with ARRDs.

Poor work outcomes in patients with spondyloarthritis: causes, consequences, and solutions.

BACKGROUND: Spondyloarthritis (SpA) affects patients in the prime of their economic productivity and can cause loss of work productivity and unemployment. We aim to identify factors associated with poor work outcomes in patients with SpA. METHODS: A cross-sectional study was performed in 100 patients with SpA who were employed, retired, or off work because of SpA. Data on sociodemographic and professional characteristics were collected as well as specific indices: BASDAI, ASDAS-CRP, BASFI, and BASMI. Work productivity in employed patients was assessed by the Work Productivity and Activity Impairment scale (WPAI:SpA). RESULTS: Patients were divided into 73 men and 27 women; the mean age was 43.68 ± 10.3 years. Fifty-nine percent of patients were employed and 26% were off work. The average disease duration was 12.24 ± 8.73 years. The mean BASDAI score was 4.4 ± 2.4, the average BASFI score was 4.6 ± 2.7, and the average ASDAS-CRP score was 2.77 ± 1.18. The mean BASMI was 4.4 ± 2.8. Among employed patients, the mean of absenteeism, presenteeism, and work productivity loss was 21.8 ± 33.13%, 42 ± 32%, and 46.5 ± 35.31%, respectively. In multivariable analysis, absenteeism was associated with ASDAS ≥ 2.1 (ß = 20.14), peripheral joint involvement (ß = 15.6), manual work (ß = 14.31), low level of education (ß = 7.92), and BASFI ≥ 4 (ß = 6.39). Presenteeism and work productivity loss were associated with manual work, BASFI ≥ , body mass index ≥ 25 kg/m2, smoking, the use of symptomatic treatment, and ASDAS-CRP ≥ 2.1. CONCLUSION: Spondyloarthritis affects work productivity. Screening for predictive factors should be considered by the clinician in the overall management of the disease. Key Points • SpA occurs among young and active patients; it could affect their professional lives and thus lead to loss of work productivity and unemployment. • The management of patients with SpA must be multidisciplinary; this includes assessing contextual factors in order to act on modifiable factors such as smoking and BMI, optimal management of the disease to maintain at least a low disease activity, and to ensure workstation layout and elimination of professional constraints that can affect work outcomes in patients with SpA.

Primitive pelvic bone hydatidosis: What an amazing extension.

Hydatidosis is an anthropozoonosis mainly encountered in pastoral areas. It mostly affects the liver, lung, and rarely the bone and the soft tissues. Skeletal involvement is usually secondary to visceral hydatidosis. We report a case of a 49-year-old man presenting with one-year history of a progressive left hip pain. On local examination, there was tenderness in the left gluteal region with reduction in the hip range of motion. Pelvic X-ray revealed an expansive bone destruction involving the left hemi pelvis without periosteal reaction. A magnetic resonance imaging showed multiple cystic lesions extending from pelvic bones to the gluteal region. The possibility of hydatid disease was raised, and hydatid serology test was positive. No visceral involvement was found by additional examinations investigations revealed visceral hydatidosis. Thus, the diagnosis of a primary bone hydatid disease was established. No surgical excision was possible, and the patient was put on Albendazole. Echinococcosis should be ruled out while dealing with progressive expansive bony lesions. Surgical management remains a challenge especially if the involvement is very extensive.

Acute transverse myelitis revealing ankylosing spondylitis: A case report and literature review.

When faced with a patient with acute myelopathy, thorough investigations should be undertaken to determine the cause. Ankylosing spondylitis should be kept in mind as a possible cause.

SFRP5 Enhances Wnt5a Induced-Inflammation in Rheumatoid Arthritis Fibroblast-Like Synoviocytes.

Background: Tissue derived fibroblast-like synoviocytes (td-FLS) are key actors in pannus formation and contribute to joint destruction and inflammation during rheumatoid arthritis (RA). Several members of the Wnt family, including Wnt5a, may contribute to RA td-FLS activation and can potentially serve as therapeutic targets. Objective: The present work aimed to investigate the expression of Wnt5a signaling elements in RA td-FLS and their potential precursors (fluid derived (fd) FLS and fibrocytes). We also studied the role of Wnt5a in RA td-FLS pro-inflammatory activity and whether the inhibitor SFRP5 could restore Wnt5a-induced synovial dysfunction in vitro. Materials and Methods: The levels of Wnt5a, SFRP5, Wnt5a receptors/coreceptors and Wnt5a pro-inflammatory targets were determined in cultured RA td-FLS, fd-FLS and fibrocytes using qPCR under basal conditions. The expression of pro-inflammatory molecules was assessed after RA td-FLS stimulation with Wnt5a and SFRP5 at different time points. Results: Our data showed that td-FLS, fd-FLS and fibrocytes from patients with RA expressed similar levels of Wnt5a and a set of Wnt5a receptors/coreceptors. We also demonstrated that Wnt5a stimulated the expression of the pro-inflammatory targets, especially IL1ß, IL8 and IL6 in RA td-FLS. Wnt5a-induced inflammation was enhanced in the presence of SFRP5. Furthermore, Wnt5a alone and in conjunction with SFRP5 inhibited the gene expression of TCF4 and the protein levels of the canonical coreceptor LRP5. Conclusion: Wnt5a pro-inflammatory effect is not inhibited but enhanced by SFRP5 in RA td-FLS. This research highlights the importance of carefully evaluating changes in Wnt5a response in the presence of SFRP5.

A Rare Case of Hypophosphataemic Osteomalacia in von Recklinghausen Neurofibromatosis.

BACKGROUND: Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is a one of the more common hereditary autosomal disorders. However, osteomalacia in neurofibromatosis type 1 is very rare tumour-induced osteomalacia; fibroblast growth factor-23 is usually implicated. PATIENTS AND METHODS: We report the case of a patient with a history of von Recklinghausen neurofibromatosis who presented with hypophosphataemic osteomalacia. RESULTS: The patient was treated with high-dose calcitriol and oral phosphate with clinical improvement. CONCLUSION: Even though it is a rare entity, we must consider the diagnosis of hypophosphataemic osteomalacia in patients with neurofibromatosis in order to deliver appropriate treatment. LEARNING POINTS: Osteomalacia during von Recklinghausen disease is a rare presentation of an uncommon condition and has a poorly understood mechanism.The treatment of oncogenic osteomalacia includes tumour removal which, however, is not always possible.Administration of calcitriol alone is not sufficient and phosphorus intake is mandatory to improve symptoms.

Multifocal tuberculosis on certolizumab pegol in a patient followed for rheumatoid arthritis.

Tuberculosis must be considered in front of deterioration in general condition in patient with rheumatic disease under biological therapy. Rheumatologists may pay attention and screen infections before and after prescribing biological therapy.

Expression of extracellular matrix components and cytokine receptors in human fibrocytes during rheumatoid arthritis.

Purpose: Fibroblast-like synoviocytes (FLS) represent one of the principal effectors of joint damage in rheumatoid arthritis (RA). Recent discovery of the circulating fibrocyte, a potential precursor of FLS, has raised issues regarding the characterization of fibrocytes with respect to their morphology and their biological role. In this study, we evaluated the morphology of fibrocytes in vitro and their ability to produce different extracellular matrix (ECM) components in comparison with two populations of RA FLS: synovial fluid FLS (fd-FLS) and intimal lining FLS (td-FLS). We also studied the expression of ECM regulators and a set of cytokine receptors involved in the pathogenesis of RA. Materials and Methods: Fibrocytes were cultured from peripheral blood of patients with RA. FLS were cultured from synovial fluids and tissues. ECM proteins (collagen I (col I) and fibronectin), Matrix metalloproteinases (MMP) (MMP3, and MMP9), ECM regulators (ß catenin, TCF4, and c-fos), and cytokine receptors (CXCR1, CXCR2, CXCR3, IL1RI, IL1RII, and IL6Rα) were analyzed using qRT-PCR and/or western blot. Results: Our results demonstrated that fibronectin and MMP3 levels were higher in FLS compared to fibrocytes. Although MMP9 was expressed in the three cell types, its level was greater in fibrocytes than in td/fd FLS. The three cell types expressed CXCR3, IL1RI, IL1RII, and IL6Rα, while the expression of CXCR1 and CXCR2 was restricted to fibrocytes. Conclusion: Our results demonstrated that fibrocytes express ECM molecules and cytokines receptors. The observed differences between fibrocytes and FLS may be due to their distinct functions or differentiation state during RA.Abbreviations: RA: Rheumatoid ArthritisFLS: fibroblast-like synoviocytestd: tissue derivedfd: fluid derivedSF: Synovial FluidWnt: WinglessMMP: Matrix MetalloproteinaseCIA: murine collagen induced arthritisECM: Extracellular matrixcol I: Collagen ITCF/LEF: T-cell factor/lymphoid enhancer-binding factorAP1: Activator Protein 1.

Mineral bone disorder and osteoporosis in hemodialysis patients.

BACKGROUND: Bone disease is common in patients undergoing hemodialysis. It is the result of bone turnover abnormalities and the decrease of bone mineral density (BMD). We aimed to determine the usefulness of serum bone turnover markers and BMD measurement by dual-energy x-ray absorptiometry (DXA) in hemodialysis patients. METHODS: We conducted a cross-sectional study including 90 hemodialysis for more than 12 months. Bone mineral density was assessed by DXA. Peripheral blood samples were obtained from each patient before dialysis in a fasting state within a week of the DXA. Biochemical variables of calcium and phosphate were measured. One bone formation marker (bone-specific alkaline phosphatase (bAP), one bone resorption marker (carboxy-terminal telopeptides of type 1 collagen (CTX)) were measured. Total alkaline phosphatase (TAP), intact parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) which is a bone-derived hormone were also measured. RESULTS: CTX values were 6.25 times higher than the normal limit of the assay. Bone alkaline phosphatase levels were less than 10 ng/mL in 28.8% of cases. 23% of patients have osteoporosis and 45% have osteopenia. Femoral BMD had negative correlations with age and PTH levels. FGF23 levels were significantly increased in patients with osteoporosis affecting the lumbar. The levels of bAP and CTX showed a positive correlation. Both circulating bAP and CTX levels showed also positive correlations with PTH levels. Fractures, observed in 12.2% of cases, were associated with low PTH values and the existence of osteoporosis. CONCLUSIONS: Our study showed that osteoporosis and fracture are common in dialysis patients. The reduced BMD was associated with advanced age and elevated levels of PTH. Markers of bone turnover and FGF23 may play a role in the diagnosis of bone disease in hemodialysis patients. DXA measurement is necessary for the monitoring for bone loss.