Increased serum levels of fractalkine and mobilisation of CD34+CD45- endothelial progenitor cells in systemic sclerosis.

BACKGROUND: The disruption of endothelial homeostasis is a major determinant in the pathogenesis of systemic sclerosis (SSc) and is reflected by soluble and cellular markers of activation, injury and repair. We aimed to provide a combined assessment of endothelial markers to delineate specific profiles associated with SSc disease and its severity. METHODS: We conducted an observational, single-centre study comprising 45 patients with SSc and 41 healthy control subjects. Flow cytometry was used to quantify circulating endothelial microparticles (EMPs) and CD34+ progenitor cell subsets. Colony-forming unit-endothelial cells (CFU-ECs) were counted by culture assay. Circulating endothelial cells were enumerated using anti-CD146-based immunomagnetic separation. Blood levels of endothelin-1, vascular endothelial growth factor (VEGF) and soluble fractalkine (s-Fractalkine) were evaluated by enzyme-linked immunosorbent assay. Disease-associated markers were identified using univariate, correlation and multivariate analyses. RESULTS: Enhanced numbers of EMPs, CFU-ECs and non-haematopoietic CD34+CD45- endothelial progenitor cells (EPCs) were observed in patients with SSc. Patients with SSc also displayed higher serum levels of VEGF, endothelin-1 and s-Fractalkine. s-Fractalkine levels positively correlated with CD34+CD45- EPC numbers. EMPs, s-Fractalkine and endothelin-1 were independent factors associated with SSc. Patients with high CD34+CD45- EPC numbers had lower forced vital capacity values. Elevated s-Fractalkine levels were associated with disease severity, a higher frequency of pulmonary fibrosis and altered carbon monoxide diffusion. CONCLUSIONS: This study identifies the mobilisation of CD34+CD45- EPCs and high levels of s-Fractalkine as specific features of SSc-associated vascular activation and disease severity. This signature may provide novel insights linking endothelial inflammation and defective repair processes in the pathogenesis of SSc.

Efficacy of Autologous Microfat Graft on Facial Handicap in Systemic Sclerosis Patients.

BACKGROUND: Autologous adipose tissue injection is used in plastic surgery for correction of localized tissue atrophy and has also been successfully offered for treatment of localized scleroderma. We aimed to evaluate whether patients with systemic sclerosis (SSc) and facial handicap could also benefit from this therapy. METHODS: We included 14 patients (mean age of 53.8 ± 9.6 years) suffering from SSc with facial handicap defined by Mouth Handicap in Systemic Sclerosis Scale (MHISS) score more than or equal to 20, a Rodnan skin score on the face more than or equal to 1, and maximal mouth opening of less than 55 mm. Autologous adipose tissue injection was performed under local anesthesia using the technique of subcutaneous microinjection. The main objective of this study was an improvement of the MHISS score 6 months after the surgical treatment. RESULTS: The procedure was well tolerated. We observed a mean decrease in the MHISS score of 10.7 points (±5.1; P < 0.0001) at 6 months (35% improvement). Secondary efficacy parameters assessing perioral skin sclerosis, maximum mouth opening, sicca syndrome, and facial pain significantly improved at 3 and 6 months postsurgery. At a 6-month follow-up, 75% of patients were satisfied or very satisfied of the adipose tissue microinjection therapy. CONCLUSIONS: Our study suggests that subcutaneous perioral microfat injection in patients with SSc is beneficial in the treatment of facial handicap, skin sclerosis, mouth opening limitation, sicca syndrome, and facial pain. Thus, this minimally invasive approach offers a new hope for face therapy for patients with SSc.

99mTc DPD is the preferential bone tracer for diagnosis of cardiac transthyretin amyloidosis.

We emphasize the role of Tc-99m-3,3-diphosphono-1,2-propanodicarboxylicacid (DPD) scintigraphy as a noninvasive tool to distinguish transthyretin (TTR)-related cardiac amyloidosis from other forms of cardiac amyloidosis. We report the case of a 76-year-old male patient suffering from congestive heart failure in whom imaging investigation by DPD scintigraphy showed a strong cardiac uptake highly suggestive of TTR amyloidosis variant. TTR-related cardiac amyloidosis was confirmed on myocardial biopsies by immunohistochemistry analysis. This case supports the growing interest in DPD scintigraphy for typing cardiac amyloidosis and for its contribution in the place of invasive myocardial biopsy.

Incidence, risk profile and morphological pattern of lower extremity venous thromboembolism after urological cancer surgery.

PURPOSE: We examined the incidence of asymptomatic and symptomatic lower extremity venous thromboembolism in patients who underwent urological surgery for cancer, and identified preoperative and operative risk factors predictive of the thromboembolism. MATERIALS AND METHODS: A cohort of 583 consecutive patients undergoing urological cancer surgery was prospectively assessed using complete lower limb ultrasound at postoperative day 7 from January 2005 to July 2009. In all patients heparin and mechanical thromboprophylaxis were prescribed until complete ambulation. Potential variables predictive of venous thrombosis were analyzed. RESULTS: Complete data were available in 538 patients (463 male and 75 female), of whom 177 underwent nephrectomy, 86 radical cystectomy and 275 radical prostatectomy. A total of 40 deep venous thrombosis cases were found (7.4%), most of which were asymptomatic (92%) and limited to deep calf veins (80%). Of those asymptomatic deep venous thrombosis cases 86% were limited to deep calf veins. In all, 12 pulmonary embolisms were diagnosed, of which 4 were lethal. On multivariate analysis history of venous thromboembolism (OR 5.16, p = 0.02) and radical cystectomy (OR 3.47, p = 0.002) were independently associated with venous thromboembolism. CONCLUSIONS: Lower extremity venous thromboembolism has a high rate of occurrence after urological surgery for cancer despite the recommended venous thromboembolism prophylaxis. Most cases are asymptomatic and limited to deep calf veins. Our results suggest that complete lower limb ultrasound should be performed early after radical cystectomy and in patients with a personal history of venous thromboembolism.

Respective roles of preterm birth and fetal growth restriction in blood pressure and arterial stiffness in adolescence.

PURPOSE: Recent studies show that low birth weight infants are at a risk of increased arterial blood pressure (BP) in adulthood. This study aimed to distinguish the influence of low birth weight either as a result of fetal growth restriction or preterm birth on arterial properties in adolescents. METHODS: The effect of low birth weight on BP and arterial stiffness was examined among 90 adolescents aged 14 years who were either born at term with an appropriate birth weight for gestational age (controls, n = 41); born preterm with an appropriate birth weight for gestational age (n = 25); or born at term and small for gestational age (SGA) (n = 24). The pulse wave velocity between the carotid and radial arteries was measured to assess arterial stiffness. RESULTS: As compared with control subjects, adolescents born with low birth weight as a result of preterm birth were found to have increased systolic BP and carotid-radial pulse wave velocity (117 ± 11 mm Hg vs. 123 ± 11 mm Hg, p = .04 and 7.0 ± .9 m/s vs. 7.7 ± 1.0 m/s, p = .01, respectively), whereas those who were born at term and SGA exhibited values similar to the controls (114 ± 15 mm Hg and 6.8 ± .9 m/s). CONCLUSION: Preterm birth, rather than being SGA at term, increases BP and arterial stiffness in adolescents.

Gender differences in artery wall biomechanical properties throughout life.

Elevated large artery stiffness and pulse pressure have emerged as important risk factors for cardiovascular disease. The genders differ in large artery biomechanical properties throughout the lifespan with females displaying higher stiffness than males during the prepubertal years and a dramatic increase after menopause. Males on the other hand experience an increase in arterial stiffness postpuberty and a linear increase thereafter, suggesting that females have intrinsically stiffer large arteries than males, but that such effects are mitigated by sex steroids during the reproductive years. This review discusses anthropometric and sex steroid influences on gender differences in large artery stiffness and pressure dynamics from childhood to senescence. In particular, the sex-specific effects of estrogen, progesterone and testosterone on vascular structure and function and how these influence arterial stiffness are explored. These factors may contribute in part to the observed gender differences in the pathophysiology and clinical manifestations of cardiovascular disease.

Lumbar septic arthritis and psoas abscess due to Aggregatibacter aphrophilus.

Invasive infections due to Aggregatibacter aphrophilus mainly include negative blood culture endocarditis and osteoarticular infections. The authors present herein a rare case of posterior septic arthritis related to A aphrophilus involving lumbar spine with contiguous abscesses of psoas and paravertebral muscles. The infection likely originated from oral cavity. A good outcome was observed after a prolonged and targeted antibiotherapy.

Endothelial function and hemodynamics in systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is characterized by the development of fibrosis of skin and internal organs that is associated with vascular damage. However, its related parameters have not been fully explored. The aim of this study was to investigate endothelial function in SSc and its relationship with systolic pulmonary artery pressure and systemic arterial compliance (SAC). METHODS: We studied 14 SSc females (4 with diffuse and 10 with limited cutaneous form of the disease) and 14 healthy controls matched for age and for cardiovascular risk factors. Endothelium-dependent dilation (i.e. flow-mediated) and endothelium-independent (i.e. nitroglycerin-induced) dilation of the brachial artery were measured as the percentage of change from baseline (FMD and NMD, respectively). In patients with SSc, SAC, cardiac output (CO), systemic arterial resistance and pulmonary artery pressure were estimated using echocardiography Doppler. RESULTS: Heart rate, brachial artery pressure and body mass index did not differ between patients with SSc and controls. Flow-mediated vasodilation (FMD) and NMD were significantly decreased in patients with SSc (10.3 ± 8.6 versus 26.6 ± 7.4%, P<0.001; 24.2 ± 8.4 versus 33.3 ± 10.1%, P<0.001, respectively). Postischaemia reactive hyperaemia was lower in patients with SSc (275 ± 185 versus 618 ± 366%, P<0.001). FMD and nitrate-mediated dilation (NMD) were associated with CO, but not with SAC; moreover, FMD correlated with pulmonary artery pressure and peripheral arterial resistance conversely to NMD. CONCLUSIONS: Endothelium function in SSc is impaired independently to SAC. Furthermore, the severity of both small artery and pulmonary artery involvement may impact on endothelium-dependent function.

Low prevalence of anti-RNA polymerase III antibodies in a French scleroderma population: anti-RNA polymerase III scleroderma.

BACKGROUND: Anti-RNA polymerase III antibodies (anti-RNAP III) have been reported as potential immune markers of Systemic Sclerosis (SSc). Until now, their clinical use was disregarded because of technical difficulties to perform immunoprecipitation. Recently, ELISA kits became commercially available allowing an easy detection of anti-RNAP III. We intended to clarify the relevance of these antibodies in the diagnosis of SSc by ELISA detection. METHODS: The prevalence of anti-RNAP III was analyzed using two ELISA kits in 50 consecutive SSc patients from Marseilles in South of France. Controls included 66 patients with other systemic autoimmune diseases, 34 viral diseases and 50 healthy subjects. Positive results with at least one ELISA kit were controlled by immunoprecipitation which is the reference assay. RESULTS: In this study, positivity for anti-centromere and/or anti-topoisomerase I antibodies was observed in 84% of SSc patients. The prevalence of anti-RNAP III in SSc patients was 0% to 6% (3/50) depending on the ELISA kit and only 2% by immunoprecipitation. Concerning controls, two rheumatoid arthritis patients were positive using ELISA (6%), including one with immunoprecipitation confirmation. No anti-RNAP III was detected in systemic lupus erythematosus patients. Three blood donors and one viral disease control were positive using ELISA, but all were negative by immunoprecipitation. CONCLUSIONS: Anti-RNAP III was rarely detected in a French population of SSc patients. Their prevalence was even lower than the one observed in rheumatoid arthritis controls. Therefore local immunologic profiles should be established before deciding a change in clinical practice for SSc immune screening.

An atypical pneumococcal arthritis.

Bone and joint infections due to Streptococcus pneumoniae usually occur in patients who are immunocompromised, and involve one site. The unique case of a 49-year-old immunocompetent man, with an unremarkable medical history, with septicaemia and polyarticular septic arthritis involving the shoulder and knee and with cervical spondylodiscitis due to S pneumoniae, is described. In this case, S pneumoniae probably originated from the gingiva, which is commonly colonised in children and adults. S pneumoniae should be considered routinely when facing bone and joint infections, and multiple locations should be carefully sought owing to the possible lack of symptoms.

Association between a CTGF gene polymorphism and systemic sclerosis in a French population.

OBJECTIVE: Systemic sclerosis (SSc) is a life-threatening autoimmune disease characterized by chronic fibrosis of the skin and internal organs. Connective tissue growth factor (CTGF) is believed to be a primary mediator of chronic fibrosis. We assessed the possible association between 7 single-nucleotide polymorphisms (SNP) in the CTGF gene and scleroderma in a French population (registration number 2006/0182). METHODS: We conducted a case-control study with 241 scleroderma patients and 269 controls. Seven SNP were genotyped using the TaqMan system. Univariate and multivariate analyses were performed. In silico electrophoretic mobility shift assay (EMSA), and reverse transcriptase polymerase chain reaction analyses were done to assess the effect of the SNP on CTGF gene expression. RESULTS: The frequency of the rs9399005TT genotype was significantly lower in SSc patients than in controls. This association remained significant after adjustment for gender. An association was detected between the rs9399005 and the diffuse and limited cutaneous forms. Multivariate analysis between SSc patients and controls taking into account all 7 SNP and sex revealed that only sex and the rs9399005 SNP were associated with disease. DNA analysis by EMSA indicated that the T allele bound nuclear factors that were also bound by the C allele. The binding affinity was higher for the T allele. Analysis of the human database and experiments with human hepatocyte cell line indicated the existence of an alternative transcript containing the rs9399005 polymorphism in its 3'UTR region. In silico analysis indicated that this polymorphism may alter the structure of CTGF messenger RNA. CONCLUSION: These findings suggest that CTGF gene polymorphisms may contribute to susceptibility to scleroderma.