Acroparesthesias: An Overview.

Acroparesthesia is a symptom characterized by a subjective sensation, such as numbness, tingling, prickling, and reduced sensation, affecting the extremities (fingers and toes). Despite its frequency, data regarding its diagnostic approach and management are scarce. The etiological diagnosis of acroparesthesia is sometimes challenging since it can be due to abnormality anywhere along the sensory pathway from the peripheral nervous system to the cerebral cortex. Acroparesthesia can reveal several diseases. It can be associated with rheumatic complaints such as arthritis or myalgia. Further cautions are required when paresthesia is acute (within days) in onset, rapidly progressive, severe, asymmetric, proximal, multifocal, or associated with predominant motor signs (limb weakness) or severe dysautonomia. Acroparesthesia may reveal Guillain-Barré syndrome or vasculitis, requiring rapid management. Acroparesthesia is a predominant symptom of polyneuropathy, typically distal and symmetric, often due to diabetes. However, it can occur in other diseases such as vitamin B12 deficiency, monoclonal gammopathy of undetermined significance, or Fabry's disease. Mononeuropathy, mainly carpal tunnel syndrome, remains the most common cause of acroparesthesia. Ultrasonography contributes to the diagnosis of nerve entrapment neuropathy by showing nerve enlargement, hypoechogenic nerve, and intraneural vascularity. Besides, it can reveal its cause, such as space-occupying lesions, anatomical nerve variations, or anomalous muscle. Ultrasonography is also helpful for entrapment neuropathy treatment, such as ultrasound-guided steroid injection or carpal tunnel release. The management of acroparesthesia depends on its causes. This article aimed to review and summarize current knowledge on acroparesthesia and its causes. We also propose an algorithm for the management of acroparesthesia.

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.

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.

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.

Increased serum interleukin 22 levels in patients with axial spondyloarthritis.

OBJECTIVES: The role of IL-22 in radiographic axial spondyloarthritis is not fully elucidated. Thus, there is a need for new insights into this cytokine in this disease. We aimed to compare interleukin (IL)-22 level between spondyloarthritis, nonspecific-low back pain patients, and pain-free controls, and to evaluate associations between this cytokine and spondyloarthritis characteristics. METHODS: We conducted a case-control study including 62 patients with radiographic axial spondyloarthritis (G1), 46 with nonspecific low back pain (G2), and 42 healthy volunteers (G3). IL-22 was measured using Enzyme-linked immunosorbent assay. We evaluate disease activity and structural damage of spondyloarthritis. RESULTS: IL-22 level was higher in G1 than in G2 and G3 (38±40 versus14.42±8.17 versus14.3±18.67 pg/mL, p<0.01). IL-22 discriminated patients in G1 from G2 with a cutoff of 22.28pg/mL (Sensitivity: 62.9%, Specificity: 97.8%, area under the curve (AUC): 0.808). IL-22 cutoff of 19.27pg/mL discriminated patients in G1 from G3 (Sensitivity: 67%, Specificity: 94.3%, AUC: 0.855). No associations were found between IL-22 levels and disease activity and structural damage. CONCLUSIONS: Our study showed that IL-22 level was higher in radiographic axial spondyloarthritis patients compared to controls. It was also able to differentiate G1 patients from G2 and G3. This finding suggests that the IL-22 pathway showed to play a pathological role in spondyloarthritis.

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.

Associated Factors with the Severity of Hip Involvement in Spondyloarthritis and Efficacy of TNF α Inhibitors in these Patients.

INTRODUCTION: Hip involvement in patients with spondyloarthritis is responsible for disability and functional impairment. Its treatment is not codified. Our study aimed to determine the associated factors with moderate and severe hip involvement in spondyloarthritis patients. It also aimed to assess the efficacy of tumour necrosis factor inhibitors (TNFi) on hip disease. METHODS: We conducted a cross-sectional study, including 44 spondyloarthritis patients with hip involvement. Hip involvement was diagnosed based on radiographic findings. We assessed the following parameters: Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Radiology Index (BASRI), patient global assessment (PGA), and Lequesne index. We compared these parameters and the mean radiographic joint space width between the time of the study to those right before the use of TNFi. RESULTS: Hip involvement was bilateral in 31 patients. The mean age was 44.56±12.21 years. There were 29 men. Severe and moderate involvement (BASRI-hip>3) was reported in 21 hips from 75 affected. These patients were older and had longer diagnosis delays than patients with BASRI- hip<3. They had a higher body mass index and more limited spine mobility (BASMI). Functional hip impairment assessed by the Lequesne index was higher in these patients. TNFi prescribed in 23 patients with hip involvement, led to an improvement in the Lequesne index (12.75 vs 7.5, p: 0.001) and PGA (7 vs 2, p: 0.001). However, the mean joint space width remained unchanged (3.8 vs 3.7mm, p: 0.532). CONCLUSION: Our study showed that higher body mass and Lequesne indexes are associated with moderate and severe hip involvement. TNFi may improve both the Lequesne index and PGA and stabilize the radiological findings.

Factors associated with hip involvement in spondyloarthritis: a retrospective study.

BACKGROUND: Hip involvement is a life-changing event during spondyloarthritis (SpA) since it's responsible for significant disability and functional impairment. This study aimed to determine the factors associated with hip involvement in patients with SpA. METHODS: This was a retrospective study, including patients with axial and/or peripheral SpA divided into two groups: patients without and with hip involvement. Hip involvement was defined as pain or abnormality on clinical examination of the hip and/or on imaging. We collected clinical and laboratory data, activity and functional scores, and radiographic parameters. We conducted a multivariate analysis to identify the associated factors of hip involvement. RESULTS: We included 165 patients with a mean age of 46.13 ± 13.07 years, 121 patients were male. The mean duration of disease was 10.91 ± 6.94 years. Hip involvement, defined as SpA-related hip pain, joint limitation, and dysfunction and/or imaging involvement (X-ray/MRI), was noted in 60 cases (36.4%). Multivariate analysis indicated that disease duration over 10 years (OR=3.847, 95% confidence interval (CI95%)[1.324-11.178], p=0.013), radiographic sacroiliitis (OR=8.949, CI95%[1.261-63.513], p=0.028), very high disease activity (Ankylosing Spondylitis Disease Activity Score: ASDASCRP≥3,5) (OR=9.364, CI95%[2.552-34.352], p=0.001), higher Bath Ankylosing Spondylitis Functional Index (BASFI) (OR=1.439, CI95%[1.120-1.850], p=0.004) and higher Bath Ankylosing Spondylitis Metrology Index (BASMI) (OR=1.311, CI95%[1.065-1.615], p=0.011) were independently associated with hip involvement in these patients. Regarding extra-articular features, we found that pulmonary involvement and osteoporosis were significantly more frequent in patients with hip involvement, but neither retained significance in multivariate analysis. CONCLUSION: Disease duration over 10 years, radiographic sacroiliitis, very high disease activity, functional impairment, and limited spine mobility were potential associated factors with hip involvement. Patients with these factors should be closely monitored to detect hip involvement at an early stage.

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.

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.

New Markers of Bone Fragility in Hemodialysis Patients: A Monocentric Study.

INTRODUCTION: Mechanisms underlying bone fragility in patients under dialysis are various. The assessment of bone disorder is not yet codified in these patients. Our study aimed to determine the relationship between the serum fibroblast growth factor 23 (FGF23) level and bone fragility. We also aimed to assess the bone alkaline phosphatase (bAP) to the C-terminal telopeptide of type I (CTX) ratio and the FGF23*bAP product to CTX ratio in patients under hemodialysis. METHODOLOGY: We conducted a cross-sectional study, including 76 patients under hemodialysis. To assess bone fragility, we measured bAP, CTX, and FGF 23. We calculated the bAP to the CTX ratio (bAP/CTX) and the FGF23*bAP product to the CTX ratio (FGF23*bAP/CTX). We defined bone fragility as the existence of osteoporosis or fragility fractures. Receiver operating characteristic (ROC) curves were evaluated for each biological using the existence of osteoporosis or fragility fracture as the gold standard for bone fragility. RESULTS: There were 51 men. The mean age was 53.36 ± 14.27 years. Bone fragility was noted in 25 cases. Patients with osteoporosis had higher FGF*bAP/CTX and bAP/CTX ratios. The ability of the ratio (bAP/CTX) to distinguish patients with osteoporosis from those without osteoporosis was good, with a ROC AUC of 0.707. The optimal ratio cut-off value with the highest accuracy was 9.72. The ability of the ratio (FGF23*bAP/CTX) to distinguish patients with bone fragility was good, with a ROC AUC of 0.701. The optimal ratio cut-off value with the highest accuracy was 1621.89 (sensitivity 60%, specificity 78.4%). CONCLUSION: Our study showed FGF23, FGF23*bAP product to CTX ratio, and the bAP to CTX ratio can be used as markers of bone fragility in hemodialysis patients. Therefore, these noninvasive and relatively inexpensive methods may serve to diagnose bone fragility in patients under hemodialysis.

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.

Mineral bone disorder and osteoporosis in hemodialysis patients

Abstract 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.(AU)

Molecular basis of complement factor I deficiency in Tunisian atypical haemolytic and uraemic syndrome patients.

AIM: The aim of the present study was to characterize the molecular basis of complement factor I deficiency in Tunisian atypical haemolytic and uremic syndrome patients with low factor I levels. METHODS: Six adults and seven children were enrolled in this study. Complement factor I levels were assessed by a homemade sandwich ELISA and ranged between 12.5% and 60%. Genomic DNA was amplified by way of a polymerase chain reaction using intronic primers flanking the 13 coding exons. Sequencing of amplified products was carried out by the dye terminator sequencing method. Molecular study was performed on parental samples for three dead paediatric patients. The control group consisted of 100 healthy Tunisian donors. RESULTS: We identified a total of 13 substitutions and one insertion: seven in introns, four in exons and three in UTR. The new mutations were c.-132G > C, c.71 + 181 T > A in 5'UTR and intron 1, respectively. Three intronic polymorphisms were predicted to have impact on splicing events: c.482 + 6C > T, c.884-42_884-41insTTAAA (rs34422850) and c.1429 + 33 A > G (rs9998151). They were three missense mutations leading to a p.Ile 357Met, p.Ile416Leu and p.GLu548Gln. p.Ile 357Met was found in two patients and one relative. Half of the patients had associated mutation and/or polymorphisms. CONCLUSION: This is the first genetic study in Tunisian and Maghrebin atypical haemolytic and uraemic syndrome patients. The high occurrence of Ile357Met mutation may reflect a founding effect. Functional impact of the two new mutations c.-132G > C and c.71 + 181A > T have to be studied. Association of simultaneous genetic abnormalities may explain the variability of atypical haemolytic and uraemic syndrome, penetrance and disease phenotype.