Characteristics and outcome of knee prosthetic joint infections (PJI): A 10-year cohort study (2000-2009)

Background: Prosthetic joint infections (PJI) lead to significant long-term morbidity with high cost of healthcare. We evaluated characteristics of infections and the infection and functional outcome of knee PJI over a 10-year period. Methods: All patients hospitalized at our institution from 1/2000 through 12/2009 with knee PJI (defined as growth of the same microorganism in ≥2 tissue or synovial fluid cultures, visible purulence, sinus tract or acute inflammation on tissue histopathology) were included. Patients, their relatives and/or treating physicians were contacted to determine the outcome. Results: During the study period, 61 patients with knee PJI were identified. The median age at the time of diagnosis of infection was 73 y (range, 53-94 y); 52% were men. Median hospital stay was 37 d (range, 1-145 d). Most reasons for primary arthroplasty was osteoarthritis (n = 48), trauma (n = 9) and rheumatoid arthritis (n = 4). 23 primary surgeries (40%) were performed at CHUV, 34 (60%) elsewhere. After surgery, 8 PJI were early (<3 months), 16 delayed (3-24 months) and 33 late (>24 months). PJI were treated with (i) open or arthroscopic debridement with prosthesis retention in 26 (46%), (ii) one-stage exchange in 1, (iii) two-stage exchange in 22 (39%) and (iv) prosthesis removal in 8 (14%). Isolated pathogens were S. aureus (13), coagulase-negative staphylococci (10), streptococci (5), enterococci (3), gram-negative rods (3) and anaerobes (3). Patients were followed for a median of 3.1 years, 2 patients died (unrelated to PJI). The outcome of infection was favorable in 50 patients (88%), whereas the functional outcome was favorable in 33 patients (58%). Conclusions: With the current treatment concept, the high cure rate of infection (88%) is associated with a less favorable functional outcome o 58%. Earlier surgical intervention and more rapid and improved diagnosis of infection may improve the functional outcome of PJI.

CPPD crystal deposition disease in patients with rheumatoid arthritis.

The aim of this study was to assess the frequency and the outcome of patients suffering from rheumatoid arthritis in which calcium pyrophosphate dihydrate (CPPD) crystal deposits were found to coexist in synovial fluid analysis. Such association was more frequent than previously believed with CPPD crystals found in 25.8% of 93 patients with rheumatoid arthritis. As a group, a trend toward a worse outcome was suggested by more frequent prostheses of the lower limb.

Adult native septic arthritis: 10 years in review in order to establish local guidelines on empiric antibiotic therapy.

Objective: Antibiotic stewardship includes development of practice guidelines incorporating local microbiology and resistance patterns. In case of septic arthritis (SA), addition of vancomycin to the empiric therapy and broad-spectrum antibiotherapy in some clinical settings are subjects of discussion. Our objective was to review the local epidemiology of native septic arthritis in adults, in order to establish local guidelines for empiric therapy. Methods: Retrospective study based on positive synovial fluid cultures and hospital discharge diagnoses of SA obtained from 1999 to 2008 in patients _16 years. Medical records were reviewed to assess the diagnosis and complete relevant clinical information. Results: During this ten-year period, we identified 233 SA on native joints in 231 patients. 107 episodes (46%) were obtained through positive synovial fluid cultures, and 126 episodes (54%) through the discharge diagnosis. 147 SA (63%) were large joint infections (LJI). 35 SA (15%) occurred in intravenous drug users. Preexisting arthropathy was present in 51% of cases. 42% of patients with small joint infection (SJI) were diabetic, vs. 23% with LJI (p = 0.003). When available, synovial fluid direct examination was positive in 35% of cases. Etiologic agents are reported in the table. Five of the 11 MRSA SA (45%) occurred in known carriers. SJI were more frequently polymicrobial (24% vs. 1%, p<0.001). For LJI, an empiric treatment with amoxicillin/clavulanate (A/C) would have been appropriate in 85% of cases. MRSA (8 cases) and tuberculous (7 cases) arthritis would have been the most frequently untreated pathogens. Addition of vancomycin to A/C in MRSA carriers would rise the adequacy to 87%. In contrast, A/C would cover only 75% of SJI (82% if restricted to non-diabetic patients). MRSA (3 cases) and P. aeruginosa (9 cases, 7 monomicrobial) would be the main untreated pathogens. An anti-pseudomonal penicillin would have been appropriate in 94% of cases of SJI (P = 0.002 vs. A/C, p = 0.19 if diabetic patients not included). Conclusions: Treatment with A/C seems adequate for empiric coverage of LJI in our setting. Broad-spectrum antibiotherapy was significantly superior for SJI in diabetic patients, due to different causative bacteria. In an area of low MRSA incidence, our results do not justify a systematic empiric therapy for MRSA, which should be considered in a known carrier.

Inflammation And Autoimmune Responses Are Independent Of Peripheral Mhc Class Ii Expression Driven By Ciita Piv In Collagen Induced Arthritis

Background In rheumatoid arthritis (RA), non-professional antigen presenting cells (APCs) such as fi broblast-like synoviocytes (FLS) can express MHC class II (MHCII) molecules and function as non-professional APCs in vitro.Objective To examine the regulation of MHCII expression in FLS and to investigate the role of FLS as non-professional APCs in collagen-induced arthritis (CIA). Methods Expression of MHCII, CIITA and Ciita isoforms pI, pIII and pIV was examined by RT-qPCR, immunohistochemistry and fl ow cytometry in human synovial tissues, arthritic mouse joints and human as well as mouse FLS. CIA was induced in mice knockout for the isoform IV of Ciita (pIV-/-), in pIV-/- mice transgenic for CIITA in the thymus (pIV-/- K14 CIITA) and in control littermates in the DBA/1 background by immunising with bovine collagen type II (CII) in complete Freund's adjuvant.Results HLA-DRA, total CIITA and CIITA pIII mRNA levels were signifi cantly increased in the synovial tissues from RA compared to osteoarthritis patients. Human FLS expressed surface MHCII via CIITA pIII and pIV, while MHCII expression in murine FLS was entirely mediated by pIV. pIV-/- mice lacked both inducible MHCII expression on non-professional APCs including FLS, and in the thymic cortex. The thymic defect in pIV-/- mice impaired CD4+ positive selection, thus protecting pIV-/- mice from CIA by preventing CD4+ T cells immune responses against CII and blocking the release of IFN-γ and IL-17 in ex vivo stimulated lymph node cells. The production of T dependent, arthritogenic anti-CII antibodies was also impaired in pIV-/- mice. A normal thymic expression of MHCII and CD4+ T cell repertoire was obtained in pIV-/- K14 CIITA Tg mice. Immune responses against CII were restored in pIV-/- K14 CIITA Tg mice, as well as the arthritis incidence and clinical severity despite the lack of MHCII expression by mouse FLS. At histology, infl ammation andneutrophils infi ltration scores were not reduced in pIV-/- K14 CIITA Tg mice, while the bone erosion score was signifi cantly lower than in controls.Conclusion Over expression of MHCII is tightly correlated with CIITA pIII in the arthritic human synovium. MHCII is induced via CIITA pIII and pIV in human FLS. In the mouse, MHCII expression in the thymic cortex and in FLS is strictly dependent upon Ciita pIV. The lack of Ciita pIV in the periphery of pIV-/- K14 CIITA Tg mice lowered the bone erosion score but did not signifi cantly protect from infl ammation and autoimmune responses in CIA.

Expression and function of the NALP3 inflammasome in rheumatoid synovium.

Summary The NACHT, LRR and PYD domains containing protein (NALP3) inflammasome is a key regulator of interleukin-1beta (IL-1beta) secretion. As there is strong evidence for a pro-inflammatory role of IL-1beta in rheumatoid arthritis (RA) and in murine models of arthritis, we explored the expression of the different components of the NALP3 inflammasome as well as other nucleotide oligomerization domain (NOD)-like receptors (NLRs) in synovium obtained from patients with RA. The expression of NLRs was also studied in fibroblast lines derived from joint tissue. By immunohistology, NALP3 and apoptosis-associated speck-like protein containing a CARD domain (ASC) were expressed in myeloid and endothelial cells and B cells. T cells expressed ASC but lacked NALP3. In synovial fibroblast lines, NALP3 expression was not detected at the RNA and protein levels and stimulation with known NALP3 agonists failed to induce IL-1beta secretion. Interestingly, we were unable to distinguish RA from osteoarthritis synovial samples on the basis of their basal level of RNA expression of known NLR proteins, though RA samples contained higher levels of caspase-1 assayed by enzyme-linked immunsorbent assay. These results indicate that myeloid and endothelial cells are the principal sources of inflammasome-mediated IL-1beta production in the synovium, and that synovial fibroblasts are unable to activate caspase-1 because they lack NALP3. The NALP3 inflammasome activity does not account for the difference in level of inflammation between RA and osteoarthritis.

Role of the inflammasome in murine experimental models of arthritis

Summary : The purpose of this study was to investigate the role of the inflammasome in human and experimental murine models (such as ΑΙΑ and K/BxN) of rheumatoid arthritis (RA)RA, affecting 1% of the population is the most frequent inflammatory disease characterized by synovial hyperplasia and cartilage and bone erosion, leading to joint destruction. In general, women are 3 times more affected by RA suggesting a role of estrogen in this disease. The inflammasome is a multiproteic complex triggering the activation of caspase-1 leading to the activation of IL-1 β, an important pro-inflammatory cytokine implicated in arthritis. The inflammasome has been implicated in several inflammatory diseases and particularly in gout. To highlight a possible role of the inflammasome in murine arthritis, we obtained ASC, caspase-1 and NALP3 +/+ and -/- littermate mice to perform ΑΙΑ and K/BxN arthritis. NALP3 -/- and caspase-1 -/- mice were as arthritic as wild type littermate mice in both ΑΙΑ and K/BxN models implicating that the NALP3 inflammasome is not involved in experimental arthritis. By contrast, ΑΙΑ severity was significantly diminished in ASC- deficient male and female mice, and in the K/BxN model, in ASC-deficient female mice. These results were supported by histological scoring and acute phase protein serum amyloid A (SAA) levels that were equivalent between NALP+/+ and NALP3-/- mice and diminished in ASC -/- mice. In ΑΙΑ and K/BxN murine experimental models, we observed a sexdependent phenotype. We studied the role of estradiol in both the ALA and the K/BxN models. Castrated female or male ASC -/- mice that received estradiol had a decreased arthritis severity. This implies a protective role of estrogen in the absence of ASC. In the ΑΙΑ model, proliferation assay were performed using splenocytes from mBSA- immunized ASC +/+ and -/- mice. The mBSA-induced proliferation was significantly lower in ASC-/- splenocytes. Moreover the CD3-specific proliferation of purified splenic Τ cells was significantly lower in ASC-/- cells. Finally, Τ cells from ASC-/- mice produced significantly decreased levels of IFN-gamma associated with increased levels of IL-10. These results imply a possible role of ASC in the TCR-signaling pathway and Τ cell cytokine production. In parallel the expression of the different inflammasome components were analyzed in biopsies from rheumatoid arthritis (RA) and osteoarthritis (OA) patiens. The expression of the 14 different NALPs, their effector protein ASC, and caspase-1 and -5 was readily measurable by RT-PCR in a similar proportion in RA and OA synovial samples, with the exception of NALP-5 and NALP-13, which weren't found in samples from either disease. The corresponding NALP1, -3, -12 and ASC proteins were expressed at similar levels in both OA and RA biopsies, as determined by immunohistochemistry and Western-blot analysis. By contrast, caspase-1 levels were significantly enhanced in RA synovial tissues compared to those from OA patients. NALP-1, -2, -3, -10, -12 and -14, as well as ASC, caspase-1, and -5 were detected in RNA from unstimulated and stimulated RA synoviocytes. In FLS, only ASC and caspase-1 were expressed at the protein level. NALP1, 3 and 12 were not detected. However, upon stimulation, no secreted IL-Ιβ was detectable in either RA or in OA synoviocytes culture medium. Résumé : Le but de ce projet était d'étudier le rôle de l'inflammasome dans des modèles expérimentaux d'arthrite tels que les modèles ΑΙΑ et K/BxN ainsi que dans la polyarthrite humaine (RA). La polyarthrite est une maladie inflammatoire très fréquente avec 1 % de la population affectée et touche 3 fois plus les femmes que les hommes, suggérant un rôle des hormones sexuelles dans cette pathologie. L'inflammasome est un complexe multiprotéique qui permet l'activation de la caspase-1, une cystéine protéase qui va ensuite cliver et activer rinterleukine-ΐβ (IL-Ιβ). L'inflammasome a été impliqué ces dernières années dans de nombreuses maladies inflammatoires notamment dans la goutte. Pour mettre en évidence un éventuel rôle de l'inflammasome dans l'arthrite expérimentale nous avons obtenu des souris déficientes pour certains des composants de l'inflammasome tels que ASC, NALP3 et caspase-1. Les souris NALP3 déficientes et caspase-1 déficientes sont aussi arthritiques que les souris wild type correspondantes que ce soit dans le modèle ΑΙΑ ou K/BxN. Par contre les souris mâles et femelles ASC-déficientes sont moins arthritiques que les souris +/+ correspondantes dans le modèle ΑΙΑ. Dans le modèle KRN, le même phénotype (diminution de la sévérité de l'arthrite) est observé uniquement chez les femelles ASC-/- Ce phénotype est corrélé avec l'histologie ainsi qu'avec le dosage du serum amyloid A (SAA) qui reflète l'inflammation systémique et qui est diminué chez les souris ASC-déficientes. Nous avons ensuite étudié le rôle de Γ estradiol (une des formes active des estrogènes) dans les modèles K/BxN et ΑΙΑ. Les souris castrées maies ou femelles déficientes pour ASC ayant reçu de l'estradiol ont une arthrite moins sévère ce qui implique que les estradiol ont un effet protecteur en l'absence de ASC. Dans le modèle ΑΙΑ, nous nous sommes aussi intéressés à la réponse immune. Des tests de prolifération ont été effectués sur des splénocytes en présence de mBSA (qui est l'antigène utilisé dans le modèle ΑΙΑ). Les splénocytes ASC -/- ont une proliferation qui est diminuée en présence de l'antigène. De plus la proliferation de cellules Τ spléniques purifiées en présence d'anti-CD3 est diminuée chez les cellules Τ ASC-/-. Ces résultats nous indiquent une éventuelle implication de ASC dans la signalisation par le récépteur des cellules T. En parallèle l'expression des différents composants de l'inflammasome a été analysée dans des biopsies de patients atteints de polyarthrite rhumatoide (RA) et d'arthrose (OA). L'expression des 14 différents NALPs, de l'adaptateur ASC, ainsi que des caspase-1 et -5 était similaires dans les échantillons RA et OA, à l'exception de NALP5 et 13 qui n'étaient pas détéctables. L'expression protéique de NALP1, 3, 12 et ASC effectuée par Western blot et immunohistochimie était similaire dans les biopsies RA et OA. Par contre la quantité de la caspase-1 mesurée par ELISA était augmentée de façon significative dans les extraits protéiques de biopsies RA. NALP-1, -2. -3, -10, -12, and -14 ainsi que ASC, caspase-1 et -5 étaient exprimés de façon similaire par les synoviocytes RA non stimulés et stimulés. Dans les synoviocytes seuls ASC et caspase-1 étaient détéctable au niveau protéique. NALP-1, -3 et -12 n'était pas détéctables. Cependant après stimulation il n'y avait d'IL-Ιβ sécrété que ce soit dans les surnageants de cultures de synoviocytes RA ou OA.

Nouvelles méthodes pour le diagnostic des infections liées aux implants [New methods for the diagnosis of implant-associated infections]

For successful treatment of prosthetic joint infection, the identification of the infecting microorganism is crucial. Cultures of synovial fluid and intraoperative periprosthetic tissue represent the standard method for diagnosing prosthetic joint infection. Rapid and accurate diagnostic tools which can detect a broad range of causing microorganisms and their antimicrobial resistance are increasingly needed. With newer diagnostic techniques, such as sonication of removed implants, microcalorimetry, molecular methods and mass spectrometry, the sensitivity has been significantly increased. In this article, we describe the conventional and newer diagnostic techniques with their advantages and potential future applications.

Failure of surgical treatment in 115 infected total hip arthroplasties - analysis of a 12-year prosthetic joint cohort study (1999-2010)

Infection of total hip arthroplasties (THA) leads to significant long-termmorbidity and high healthcare costs. We evaluated the differentreasons for treatment failure using different surgical modalities in a12-year prosthetic joint infection cohort study.Method: All patients hospitalized at our institution with infected THAwere included either retrospectively (1999-2007) or prospectively(2008-2010). THA infection was defined as growth of the same microorganismin ≥2 tissue or synovial fluid culture, visible purulence, sinustract or acute inflammation on tissue histopathology. Outcome analysiswas performed at outpatient visits, followed by contacting patients,their relatives and/or treating physicians afterwards.Results: During the study period, 117 patients with THA were identified.We exclude 2 patients due to missing data. The median age was69 years (range, 33-102 years); 42% were women. THA was mainlyperformed for osteoarthritis (n = 84), followed by trauma (n = 22),necrosis (n = 4), dysplasia (n = 2), rheumatoid arthritis (n = 1), osteosarcoma(n = 1) and tuberculosis (n = 1). 28 infections occurred early(≤3 months), 25 delayed (3-24 months) and 63 late (≥24 months aftersurgery). Infected THA were treated with (i) two-stage exchange in59 patients (51%, cure rate: 93%), (ii) one-stage exchange in 5 (4.3%,cure rate: 100%), (iii) debridement with change of mobile parts in18 (17%, cure rate: 83%), (iv) debridement without change of mobileparts in 17 (14%, cure rate: 53% ), (v) Girdlestone in 13 (11%, curerate: 100%), and (vi) two-stage exchange followed by removal in 3(2.6%). Patients were followed for a mean of 3.9 years (range, 0.1 to 9years), 7 patients died unrelated to the infected THA. 15 patients (13%)needed additional operations, 1 for mechanical reasons (dislocationof spacer) and 14 for persistent infection: 11 treated with debridementand retention (8 without change and 3 with change of mobile parts)and 3 with two-stage exchange. The mean number of surgery was 2.2(range, 1 to 5). The infection was finally eradicated in all patients, butthe functional outcome remained unsatisfactory in 20% (persistentpain or impaired mobility due to spacer or Girdlestone situation).Conclusions: Non-respect of current treatment concept leads totreatment failure with subsequent operations. Precise analysis of eachtreatment failures can be used for improving the treatment algorithmleading to better results.

Inflammatory role of ASC in antigen-induced arthritis is independent of caspase-1, NALP-3, and IPAF.

Because IL-1beta plays an important role in inflammation in human and murine arthritis, we investigated the contribution of the inflammasome components ASC, NALP-3, IPAF, and caspase-1 to inflammatory arthritis. We first studied the phenotype of ASC-deficient and wild-type mice during Ag-induced arthritis (AIA). ASC(-/-) mice showed reduced severity of AIA, decreased levels of synovial IL-1beta, and diminished serum amyloid A levels. In contrast, mice deficient in NALP-3, IPAF, or caspase-1 did not show any alteration of joint inflammation, thus indicating that ASC associated effects on AIA are independent of the classical NALP-3 or IPAF inflammasomes. Because ASC is a ubiquitous cytoplasmic protein that has been implicated in multiple cellular processes, we explored other pathways through which ASC may modulate inflammation. Ag-specific proliferation of lymph node and spleen cells from ASC-deficient mice was significantly decreased in vitro, as was the production of IFN-gamma, whereas IL-10 production was enhanced. TCR ligation by anti-CD3 Abs in the presence or absence of anti-CD28 Abs induced a reduction in T cell proliferation in ASC(-/-) T cells compared with wild-type ones. In vivo lymph node cell proliferation was also significantly decreased in ASC(-/-) mice, but no effects on apoptosis were observed either in vitro or in vivo in these mice. In conclusion, these results strongly suggest that ASC modulates joint inflammation in AIA through its effects on cell-mediated immune responses but not via its implication in inflammasome formation.

SOMATIC MUTATIONS IN THE KREBS CYCLE ENZYME ISOCITRATE DEHYDROGENASE 1 (IDH1) CAUSE METAPHYSEAL ENCHONDROMATOSIS WITH D-2-HYDROXYGLUTARIC ACIDURIA

Metaphyseal chondromatosis with hydroxyglutaric aciduria (MC-HGA) is a generalized skeletal dysplasia, accompanied by urinary excretion of D-2- hydroxyglutarate (HGA), and variable cerebral involvement. By wholeexome sequencing 2 unrelated patients with MC-HGA, we have found mutations in isocitrate dehydrogenase 1 (IDH1) at codon 132, as apparent somatic mosaicism. IDH1 is a key enzyme of the Krebs cycle, which converts isocitrate into alpha-ketoglutarate (a-KG). Mutations at IDH1 Arg132 residue have originally been identified in different tumour types (isolated gliomas, leukemias, and chondrosarcomas). These mutations trans-specify the enzyme activity resulting in HGA accumulation and a-KG depletion. This induces activation of hypoxia-inducible factor 1-alpha (HIF-1a), an important regulator of chondrocyte proliferation at the growth plate. Differently from Arg132 somatic mutations found in isolated tumours, themutation in our patientsmust have occurred very early in embryogenesis to cause a generalized dysplasia with involvement of all long bones metaphyses and mutation detectability in blood. Identical mutations have subsequently been identified in chondromas excised from patients with multiple chondromatosis (Ollier disease). Tissue distribution of themutationmay explain variable cerebral involvement and the susceptibility to develop tumours in other organs. The postulated pathophysiology ofMC-HGA points out the link between Krebs cycle, hypoxia sensing and bone growth.

Amyloid arthropathy in patients undergoing periodical haemodialysis for chronic renal failure: a new complication.

Seven patients (five male and two female) with chronic renal failure (CRF) treated by periodical haemodialysis presented with swelling and effusion of more than three months' duration in knees (four bilateral), shoulders (two, one of them bilateral), elbow (one), and ankle (one). Four had a carpal tunnel syndrome both clinically and electromyographically (three bilateral). All patients had hyperparathyroidism secondary to their CRF, which was not due to amyloidosis in any of them. The dialysis duration period varied from five to 14 years, with an average of 8.6 years. Amyloid deposits (Congo red positive areas with green birefringence under polarising microscopy) were shown in six of the seven synovial biopsy specimens of the knee, in five of the sediments of the synovial fluids, and in specimens removed during carpal tunnel syndrome surgery. No amyloid was found in the biopsy specimen of abdominal fat of six of the patients. The finding of amyloid only in the synovial membrane and fluid, and carpal tunnel, its absence in abdominal fat, and the lack of other manifestations of generalised amyloidosis (cardiomyopathy, malabsorption syndrome, macroglossia, etc.) and of Bence Jones myeloma (protein immunoelectrophoresis normal) raises the possibility that this is a form of amyloidosis which is peculiar to CRF treated by periodical haemodialysis.

Postmortem diagnosis of hypothermia.

The identification of hypothermia as the cause of death has always been somewhat problematic in forensic pathology because of unspecific, inconstant, or even negative macroscopic and microscopic findings. Though the simultaneous presence of frost erythema, Wischnewski spots, hemorrhages into the synovial membrane, bloody discoloration of synovial fluid of the knee, and basal vacuolization of the renal tubular epithelial cells has been indicated as strongly supportive of fatal hypothermia, their absence does not allow the diagnosis of hypothermia to be ruled out. Postmortem biochemical investigations are valuable in detecting adaptation responses to cold stress and metabolic changes that occur following cold exposure. However, ethanol intoxication prevents appearance of adaptation responses to cold, rendering the diagnosis less obvious. Immunohistochemistry, postmortem imaging, and molecular pathology have shown promising results, although at present, they do not provide pathognomonic signs of fatal hypothermia. The aim of this article is to present a review of the literature covering the significance of different postmortem investigations that are associated with hypothermia fatalities.

Myeloid-related proteins 8 and 14 contribute to monosodium urate monohydrate crystal-induced inflammation in gout.

OBJECTIVE: Monosodium urate monohydrate (MSU) crystal-induced interleukin-1β (IL-1β) secretion is a critical factor in the pathogenesis of gout. However, without costimulation by a proIL-1β-inducing factor, MSU crystals alone are insufficient to induce IL-1β secretion. The responsible costimulatory factors that act as a priming endogenous signal in vivo are not yet known. We undertook this study to analyze the costimulatory properties of myeloid-related protein 8 (MRP-8) and MRP-14 (endogenous Toll-like receptor 4 [TLR-4] agonists) in MSU crystal-induced IL-1β secretion and their relevance in gout. METHODS: MRP-8/MRP-14 was measured in paired serum and synovial fluid samples by enzyme-linked immunosorbent assay (ELISA) and localized in synovial tissue from gout patients by immunohistochemistry. Serum levels were correlated with disease activity, and MSU crystal-induced release of MRPs from human phagocytes was measured. Costimulatory effects of MRP-8 and MRP-14 on MSU crystal-induced IL-1β secretion from phagocytes were analyzed in vitro by ELISA, Western blotting, and polymerase chain reaction. The impact of MRP was tested in vivo in a murine MSU crystal-induced peritonitis model. RESULTS: MRP-8/MRP-14 levels were elevated in the synovium, tophi, and serum of patients with gout and correlated with disease activity. MRP-8/MRP-14 was released by MSU crystal-activated phagocytes and increased MSU crystal-induced IL-1β secretion in a TLR-4-dependent manner. Targeted deletion of MRP-14 in mice led to a moderately reduced response of MSU crystal-induced inflammation in vivo. CONCLUSION: MRP-8 and MRP-14, which are highly expressed in gout, are enhancers of MSU crystal-induced IL-1β secretion in vitro and in vivo. These endogenous TLR-4 ligands released by activated phagocytes contribute to the maintenance of inflammation in gout.

Lytic lesions of the femoral neck in rheumatoid arthritis simulating pigmented villonodular synovitis or malignancy

Large lytic lesions, relatively asymptomatic, involving the femoral neck and the base of the head are described in two patients suffering from a classical seropositive rheumatoid arthritis. Histological examination failed to reveal signs of malignancy, infection or pigmented villonodular synovitis. There were no rheumatoid nodules but a chronic hypertrophic villous synovitis was found. Rheumatoid synovium may invade the superior extremity of the femur; this fact is important in the differential diagnosis of destructive lesions of the femoral neck in RA.

Pie plano astrágalo vertical asociado a sinovitis. Fases de tratamiento

El pie plano astrágalo vertical congénito es una deformidad poco frecuente que se puede encontrar de forma aislada, dentro de un cuadro polimalformativo o en relación con afectaciones neurológicas. Se caracteriza por una luxación del escafoides por encima del astrágalo,lo que provoca un pie rígido o de dificil manipulación. En este artículo los autores describen un caso clínico de un paciente que acude a consulta por presentar una inflamación dolorosa en la zona de la cabeza del astrágalo del pie derecho. Una vez realizado todo el protocolo exploratorio, se plantea la resolución mediante un plan de tratamiento en dos fases: una primera fase consistente en la realización de paracentesis evacuadora o terapéutica-curativa; y una segunda fase en la que se diseña tratamiento ortopodológlco de descarga.