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.

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.

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.

[Fournier's gangrene : what are the prognostic factors? Our experience with 40 patients].

BACKGROUND: Fournier's gangrene (FG) is a serious, extensive fulminant infection of the genitals and perineum. Indeed, despite antibiotics and aggressive debridement, the mortality rate of FG remains high. AIM: Through our experience, we intent to identify effective factors in the survival of patients with FG and we try to determine how the Fournier's gangrene severity index score (FGSIS) is accurate. METHODS: Between 1995 and 2010, 40 patients with Fournier's gangrene were treated in our institution. All of them were treated with broad spectrum triple antimicrobial therapy, broad debridement and exhaustive cleaning. Then they underwent skin grafts or delayed closure as needed. Data were collected on demographics, medical history, predisposing factors of FG, etiological infection agents, admission signs and symptoms, physical examination, admission laboratory studies and bacteriology. Timing and degree of surgical debridement as well as outcomes were also reviewed. The extent of disease was calculated from body surface area nomograms. RESULTS: All the 40 patients included in this study were males; their mean age was 52,75 years (21-75 years). Twelve patients (30%) had FG secondary to anorectal pathological conditions. No etiologic factors of FG were found in 6 patients (15%). Diabetes mellitus as predisposing factor was found in 13 patients (32.5%). The mean hospital stay was 8.72 days (range, 3 to 30). All the patients underwent surgical debridement. Orchidectomy was done in 7 cases (17.5%). Skin grafts were applied to 6 patients (15%) and the remaining wounds, once cleaned, were approximated. The overall mortality rate was 17.5% (7 patients) due to severe metabolic acidosis in relation to diabetic decompensation and sepsis. We individualized two groups: those who died (n = 7) and those who survived (n = 33). We evaluated the admission laboratory parameters that are significantly correlated with outcome included hematocrit (p=0.003) and serum sodium (p=0.05). The extent of body surface area involved among patients who died was not found significantly different statistically between the two groups (4.07% and 3,14%, p=0,4). The mean FGSIS (without counting bicarbonate serum level) for survivors was 9.1 compared with 6,8 for nonsurvivors (p=0.16). CONCLUSION: FG is a rapidly progressive, fulminant infection's condition. Hematocrit and serum sodium levels were found to be the only prognostic factors. It doesn't seem that the FGSIS has a prognostic value.

Nonunion of the scaphoid treated by anterior vascularized bone graft: a review of 26 cases.

OBJECTIVE: To evaluate the clinical and radiological outcome of anterior vascularized bone graft in the treatment of primitive nonunion of the scaphoid. METHODS: This is a retrospective study of 26 scaphoid nonunion cases treated by this technique between 2004 and 2009. The mean age was 38 years. Nonunion was of types IIA and IIB according to the Alnot's classification and only one case showed a proximal pole necrosis (type IV). The fixation was ensured by K-wire. The mean immobilization period was 9 weeks. RESULTS: At mean 19 months follow-up, the bone union rate was 88.5%. Failure was noted in three cases. No significant complications secondary to this technique were observed. The mobility in extension and flexion had an average recovery of 18 degree Nineteen patients (73%) were free of pain, and the others had occasional pain. CONCLUSIONS: It is a meticulous surgical technique that provides better union rates than those of conventional scaphoid graft. This technique is first adopted in cases of failure of conventional grafts in the treatment of scaphoid nonunion but the encouraging results suggest expanding indications to primitive nonunion.

[Pseudotumoral villonodular synovitis : a case report]. / La synovite villonodulaire pseudotumorale : à propos d'un cas.

BACKGROUND: Pseudotumoral pigmented villonodular synovitis is rare and diagnosis is difficult. AIM: Report of new case. CASE: We report an original observation of a pseudotumoral pigmented villonodular synovitis occurred in a 28 years old patient with no recurrence after surgical treatment. A review of the literature was made in order to precise the epidemiological, diagnostic and therapeutic characteristics.

Upper limb compartment syndrome after an adder bite: a case report.

Compartment syndrome after an adder bite is extremely rare, whose effects are only secondary to the cytotoxic and hemorrhagic effects of venom. Here we reported a case of compartment syndrome in the upper limb following an adder bite in the thenar eminence. Elevated compartment pressure was documented and immediate surgical fasciotomy was practiced. The patient achieved complete recovery with a good functional result. We discussed the controversies on fasciotomy and non-invasive measures in such a situation, and recommended intracompartmental pressure monitoring during the management of compartment syndrome following adder bites.

[Osteomalacia and giant cell tumor: a rare case]. / Ostéomalacie et tumeur a cellule géante: une entité rare.

BACKGROUND: Oncogenic octeomalacia is an unusual and rare clinicopathologic syndrome characterized by mesenchymal tumors that apparently produce osteomalacia and biochemical abnormalities consisting of hypophosphatemia and normocalcemia. AIM: We have investigated the mechanism by which a giant cell tumor of bone caused biopsy-proved osteomalacia in a 50-year-old woman. CASE REPORT: A 50-year-old woman presented with generalized bone and pelvicrural pain, associated with fatiguability and muscle weakness. The diagnosis of osteomalacia was retained, associated with a giant cell tumor. The coexistence of giant cell tumor of bone and osteomalacia suggested the diagnosis of oncogenic osteomalacia. Resolution of the biochemical abnormalities of the syndrome after tumor resection, established this diagnosis. CONCLUSION: oncogenic osteomalacia can be a form of vitamin-D-refractory osteomalacia due to altered vitamin D3 metabolism.

[About a short series of Swanson arthroplasty]. / A propos d'une courte série d'arthroplastie de swanson.

The authors report a series of 12 patients who underwent digital arthroplasty using a swanson implant. Six patients had the sequellae of an injured hand, and the other six patients had rheumatoid arthritis. The majority of patients were men with an average age of 33 years. The patients were examined again about 4 years later on average. The lateral stability of the operated finger was considered to be satisfactory in 11 cases. The mean movement gain was 40 degrees. There was no sign of silicone particle synovitis, because it was fixed arthroplasty.

[The sacrified of sacrifice day]. / Les sacrifies de la fete du sacrifice.

This prospective study was carried out in the plastic and reconstructive surgery department of Kassab's hospital in Tunis and the hospital of Monastir (Tunisa) during the sacrifice day (Aïd el kebir). The study involved 50 patients. Our purpose was to identify the injuries of the hand occurring during this religions festival. The average age of patients was 39 years with sex ratio of 1.17. All socials and occupational sectors were affected. The lesions concern the dorsal face of non dominant hand (72%) with a peak in the frequency for the thumb (40%) and the index (37%). Extensor system of the radial finger on the non dominant hand was the main delicate element witch is most exposed during such festival. The thumb is being worthy of special mention, for it is the most serious lesions (amputation 10%) The lesions of flexor tendons are generally associated with nerve and vascular injury. 46% of patients had to undergo surgery.

[Central agenesis of the hand]. / Les agénésies centrales de la main.

Central aplasia represent under 10% of congenital malformations of the hand. It is characterised by the partial or complete absence of the median ray. We adopted the classification of Swanson and considered this anomaly a stop of median longitudinal development. We separate 2 groups: Hand in folk: the aplasia interested only the median digits, all metacarpal are present. Hand in lobster's pincer: all median rays are absent including the metacarpal. We report a set of 16 children carriers of 23 central aplasia of the hand, it was about 14 hands in lobster'pincer and 9 hands in folk. In any case, the gene was merely aesthetic, the hand's function was complete. A child has been operated, and benefitted a closing of the median crack defect, he had a free thumb. For the other cases, abstention has been decided, indeed to close this cracks deprive these hands of a first corner the alone present.