Elevated Expression of CCN3 in Articular Cartilage Induces Osteoarthritis in Hip Joints Irrespective of Age and Weight Bearing.

Osteoarthritis (OA) occurs not only in the knee but also in peripheral joints throughout the whole body. Previously, we have shown that the expression of cellular communication network factor 3 (CCN3), a matricellular protein, increases with age in knee articular cartilage, and the misexpression of CCN3 in cartilage induces senescence-associated secretory phenotype (SASP) factors, indicating that CCN3 promotes cartilage senescence. Here, we investigated the correlation between CCN3 expression and OA degenerative changes, principally in human femoral head cartilage. Human femoral heads obtained from patients who received total hip arthroplasty were categorized into OA and femoral neck fracture (normal) groups without significant age differences. Gene expression analysis of RNA obtained from femoral head cartilage revealed that CCN3 and MMP-13 expression in the non-weight-bearing part was significantly higher in the OA group than in the normal group, whereas the weight-bearing OA parts and normal cartilage showed no significant differences in the expression of these genes. The expression of COL10A1, however, was significantly higher in weight-bearing OA parts compared with normal weight-bearing parts, and was also higher in weight-bearing parts compared with non-weight-bearing parts in the OA group. In contrast, OA primary chondrocytes from weight-bearing parts showed higher expression of CCN3, p16, ADAMTS4, and IL-1ß than chondrocytes from the corresponding normal group, and higher ADAMTS4 and IL-1ß in the non-weight-bearing part compared with the corresponding normal group. Acan expression was significantly lower in the non-weight-bearing group in OA primary chondrocytes than in the corresponding normal chondrocytes. The expression level of CCN3 did not show significant differences between the weight-bearing part and non-weight-bearing part in both OA and normal primary chondrocytes. Immunohistochemical analysis showed accumulated CCN3 and aggrecan neoepitope staining in both the weight-bearing part and non-weight-bearing part in the OA group compared with the normal group. The CCN3 expression level in cartilage had a positive correlation with the Mankin score. X-ray analysis of cartilage-specific CCN3 overexpression mice (Tg) revealed deformation of the femoral and humeral head in the early stage, and immunohistochemical analysis showed accumulated aggrecan neoepitope staining as well as CCN3 staining and the roughening of the joint surface in Tg femoral and humeral heads. Primary chondrocytes from the Tg femoral head showed enhanced expression of Ccn3, Adamts5, p16, Il-6, and Tnfα, and decreased expression of Col2a1 and -an. These findings indicate a correlation between OA degenerative changes and the expression of CCN3, irrespective of age and mechanical loading. Furthermore, the Mankin score indicates that the expression level of Ccn3 correlates with the progression of OA.

eNAMPT Is Localised to Areas of Cartilage Damage in Patients with Hip Osteoarthritis and Promotes Cartilage Catabolism and Inflammation.

Obesity increases the risk of hip osteoarthritis (OA). Recent studies have shown that adipokine extracellular nicotinamide phosphoribosyltransferase (eNAMPT or visfatin) induces the production of IL-6 and matrix metalloproteases (MMPs) in chondrocytes, suggesting it may promote articular cartilage degradation. However, neither the functional effects of extracellular visfatin on human articular cartilage tissue, nor its expression in the joint of hip OA patients of varying BMI, have been reported. Hip OA joint tissues were collected from patients undergoing joint replacement surgery. Cartilage explants were stimulated with recombinant human visfatin. Pro-inflammatory cytokines and MMPs were measured by ELISA and Luminex. Localisation of visfatin expression in cartilage tissue was determined by immunohistochemistry. Cartilage matrix degradation was determined by quantifying proteoglycan release. Expression of visfatin was elevated in the synovial tissue of hip OA patients who were obese, and was co-localised with MMP-13 in areas of cartilage damage. Visfatin promoted the degradation of hip OA cartilage proteoglycan and induced the production of pro-inflammatory cytokines (IL-6, MCP-1, CCL20, and CCL4) and MMPs. The elevated expression of visfatin in the obese hip OA joint, and its functional effects on hip cartilage tissue, suggests it plays a central role in the loss of cartilage integrity in obese patients with hip OA.

Detecting Periprosthetic Joint Infection by Using Mass Spectrometry.

BACKGROUND: Novel methods for diagnosing periprosthetic joint infection (PJI) are currently being explored. Mass spectrometry (MS) is an approach that can detect whole-protein changes in synovial fluid and may represent a promising method. METHODS: Between March 2017 and July 2018, we successively collected synovial fluid samples from patients who were undergoing diagnostic hip or knee aspiration because PJI was suspected. A PJI diagnosis was based on the modified Musculoskeletal Infection Society (MSIS) criteria. Cluster analysis and receiver operating characteristic (ROC) curves were used to evaluate the results, which were quantitatively confirmed with parallel reaction monitoring in another patient group who underwent aspiration between August 2018 and January 2019. RESULTS: A total of 117 synovial samples, including 51 PJI and 66 non-PJI samples, were analyzed with liquid chromatography-tandem MS (LC-MS/MS). The cluster analysis sensitivity and specificity based on differentially expressed proteins were 0.961 (95% confidence interval [CI], 0.854 to 0.993) and 0.924 (95% CI, 0.825 to 0.972), respectively. Myeloid nuclear differentiation antigen (MNDA) and polymorphonuclear leukocyte serine protease 3 (PRTN3) were the 2 most important markers for detecting PJI. The areas under the curves (AUCs) of MNDA and PRTN3 were 0.969 (95% CI, 0.936 to 1.000) and 0.900 (95% CI, 0.844 to 0.956), respectively. When MNDA and PRTN3 were combined as variables of a predictive model to diagnose PJI, the AUC reached 0.975 (95% CI, 0.943 to 1.000). Our parallel reaction monitoring-based quantitative analysis of another 40 synovial samples confirmed this result. CONCLUSIONS: MS could be a powerful tool for diagnosing PJI using proteome information or 2 specific markers, MNDA and PRTN3. The parallel reaction monitoring strategy simplified the PJI detection process and provided quantitative results with similar conclusions. CLINICAL RELEVANCE: The clinical application of MS adds a new powerful tool for the diagnosis of PJI, and the parallel reaction monitoring strategy lays a foundation for the clinical application of MS. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Proteomics analysis of hip articular cartilage identifies differentially expressed proteins associated with osteonecrosis of the femoral head.

OBJECTIVE: The cartilage degeneration that accompanies subchondral bone necrosis plays an important role in the development of osteonecrosis of femoral head (ONFH). To better understand the molecular basis of cartilage degradation in ONFH, we compared the proteomic profiles of ONFH cartilage with that of fracture control. DESIGN: Hip cartilage samples were collected from 16 ONFH patients and 16 matched controls with femoral neck fracture. Proteomics analysis was conducted using tandem mass tag-based quantitation technique. Gene ontology (GO) analysis, KEGG pathway and protein-protein interaction analysis were used to investigate the functions of the altered proteins and biological pathways. Differentially expressed proteins including alpha-2-HS-glycoprotein (AHSG) and Cytokine-like protein 1 (Cytl1) were validated by Western blot (WB) and immunohistochemistry (IHC). RESULTS: 303 differentially expressed proteins were identified in ONFH cartilage with 72 up-regulated and 231 down-regulated. Collagen turnover, glycosaminoglycan biosynthesis, metabolic pathways, and complement and coagulation cascades were significantly modified in ONFH cartilage. WB and IHC confirmed the increased expression of AHSG and decreased expression of Cytl1 in ONFH cartilage. CONCLUSIONS: Our results reveal the implication of altered protein expression in the development of ONFH, and provide novel clues for pathogenesis studies of cartilage degradation in ONFH.

Circ_0088194 Promotes the Invasion and Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes via the miR-766-3p/MMP2 Axis.

Dysregulation of circular RNAs (circRNAs) is involved in various human diseases. Fibroblast-like synoviocytes (FLSs), which form the lining of the joint, are epigenetically imprinted with an aggressive phenotype and contribute to joint destruction in rheumatoid arthritis (RA). In the present study, we identified a novel circRNA, Circ_0088194, which was upregulated in RA fibroblast-like synoviocytes (RA-FLSs) and correlated with the disease activity score in 28 joints. Overexpression of Circ_0088194 promoted RA-FLS migration and invasion, while inhibition of Circ_0088194 had the opposite effect. Mechanistically, Circ_0088194 acted as a miR-766-3p sponge to relieve the repressive effect of miR-766-3p on its target, MMP2 (encoding matrix metalloproteinase 2), thereby promoting migration and invasion. The expression level of Circ_0088194 was inversely correlated with that of miR-766-3p in RA-FLSs. Importantly, overexpression of miR-766-3p partially blocked the migration and invasion induced by Circ_0088194 overexpression. Collectively, this study identified a novel circRNA Circ_0088194 that promotes RA-FLS invasion and migration via the miR-766-3p/MMP2 axis. Circ_0088194 might represent a novel therapeutic target to prevent and treat RA.

The Glycosaminoglycan Content of Hip Cartilage in Osteonecrosis of Femoral Head: Evaluation with Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage.

OBJECTIVE: Hip cartilage quality is essential for the success of joint-preserving surgery for osteonecrosis. This study aimed to characterize cartilage changes in osteonecrosis of femoral head (ONFH) using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC). DESIGN: Fifteen asymptomatic (control) and 60 ONFH subjects were included in this study. The ONFH subjects were stratified in accordance with the Association Research Circulation Osseous (ARCO) classification (n = 15 hips per ARCO stage). All participant hips were investigated using dGEMRIC and theT1Gd data were collected and analyzed. RESULTS: T1Gd value was significantly lower in the ONFH group (365.1 ± 90.5 ms; range 200-498 ms) compared with the control group (546.1 ± 26.0 ms; range 504-580 ms) (P < 0.001). The T1Gd values of ARCO stage I-IV ONFH were 460.2 ± 17.3 ms (439-498 ms), 408.9 ± 43.4 ms (337-472 ms), 359.9 ± 34.5 ms (303-412 ms), 231.5 ± 15.1 ms (200-253 ms), respectively. Decreased T1Gd value was found to correlate significantly with increased ONFH severity (P < 0.001). T1Gd value in collapse stage was significantly lower than that of noncollapse stage (295.7 ± 70.3 ms [range 200-412 ms] vs. 434.6 ± 41.7 ms [range 337-498 ms]; P < 0.001). CONCLUSIONS: dGEMRIC identified hip cartilage as abnormal in ONFH, even at early-stage, as represented by decreased T1Gd, and this was further aggravated by ONFH collapse.

Piezo2 expressed in proprioceptive neurons is essential for skeletal integrity.

In humans, mutations in the PIEZO2 gene, which encodes for a mechanosensitive ion channel, were found to result in skeletal abnormalities including scoliosis and hip dysplasia. Here, we show in mice that loss of Piezo2 expression in the proprioceptive system recapitulates several human skeletal abnormalities. While loss of Piezo2 in chondrogenic or osteogenic lineages does not lead to human-like skeletal abnormalities, its loss in proprioceptive neurons leads to spine malalignment and hip dysplasia. To validate the non-autonomous role of proprioception in hip joint morphogenesis, we studied this process in mice mutant for proprioceptive system regulators Runx3 or Egr3. Loss of Runx3 in the peripheral nervous system, but not in skeletal lineages, leads to similar joint abnormalities, as does Egr3 loss of function. These findings expand the range of known regulatory roles of the proprioception system on the skeleton and provide a central component of the underlying molecular mechanism, namely Piezo2.

The bone mineral density of hip joint was reduced in the initial stage of ankylosing spondylitis?

The osteoporosis was common complication of ankylosing spondylitis (AS), but it was frequently unrecognized in the initial stage of the disease. This study was to compare areal bone mineral density (BMD) of hip joints in early AS patients with that in healthy controls, to explore the progress of bone loss in cortex and spongiosa in early AS.Quantitative computed tomography (QCT) of hip was performed in 60 AS patients (modified New York criteria for AS, with grade 2 sacroiliitis in computed tomography) and 57 healthy controls. The QCT measurements of AS patients were compared with the measurements of healthy controls.The AS patients had lower areal BMD in cortical bone and total bone of proximal femur in early AS patients (P < .01), than the controls. But there were not significant different of areal BMD in spongiosa of proximal femur between the early AS patients and healthy controls. Strong correlations were found between body mass index BMI, areal BMD in cortical bone (rs = 0.410, P < .001; rs = 0.422, P < .001) and total bone (rs = 0.368, P < .001; rs = 0.266, P = .003) both in AS patients and healthy controls.The results indicate that osteopenia/osteoporosis is general in early stage of AS. What is more, the osteopenia/osteoporosis in cortex is earlier than in spongiosa of proximal femur in early AS.

Proximal femur fat fraction variation in healthy subjects using chemical shift-encoding based MRI.

The objective of this study was to describe the normal variation of bone marrow fat content in the proximal femur considering the influence of side, age, sex and body mass index using fat fraction MRI. From September 2012 to July 2016, the MRI of 131 patients (258 hips) considered to have a normal MRI appearance were retrospectively evaluated. Patient records were searched to allow calculation of the body mass index (BMI). Water-fat based chemical shift MRI was available for all patients included. Proton density fat fraction maps were calculated, and measurements were performed in the femoral epiphysis, intertrochanteric region, and greater trochanter. The influence of patient age, sex, hip side and BMI on fat fraction values was assessed. Fat fraction was significantly different in the different locations evaluated (P = 0.0001). Patient sex and age significantly influenced fat fraction values in all regions evaluated (P < 0.02) with the exception of the epiphysis for sex (p = 0.07). In all locations, PDFF values were higher in men compared to women (3.3%, 4.4% and 13.1% higher in the epiphysis, greater trochanter and intertrochanteric region respectively). The intertrochanteric region presented the lowest fat fraction values with the highest variation compared to the greater trochanter and the epiphysis. BMI only influenced fat fraction values in the intertrochanteric region of females over 42 years old (P = 0.014). The interobserver variability of the measurements performed was considered to be excellent (ICC = 0.968). In conclusion, patient sex, age, and measurement location significantly influenced fat fraction values indicating that specific standards of reference are needed depending on these factors.

Cartilage-gut-microbiome axis: a new paradigm for novel therapeutic opportunities in osteoarthritis.

DNA of gut microbiota can be found in synovium of osteoarthritis and rheumatoid arthritis. This finding could result from the translocation of still alive bacteria from gut to joints through blood, since the diversified dormant microbiota of healthy human blood can be transiently resuscitated in vitro. The recent finding of gut microbiome in human cartilage, which differed between osteoarthritis and controls, suggests that a similar trafficking of dead or alive bacteria from gut microbiota physiologically occurs between gut and epiphysial bone marrow. Subchondral microbiota could enhance cartilage healing and transform components of deep cartilage matrix in metabolites with immunosuppressive properties. The differences of microbiome observed between hip and knee cartilage, either in osteoarthritis or controls, might be the counterpart of subtle differences in chondrocyte metabolism, themselves in line with differences in DNA methylation according to joints. Although bacteria theoretically cannot reach chondrocytes from the surface of intact cartilage, some bacteria enter the vascular channels of the epiphysial growth cartilage in young animals, whereas others can infect chondrocytes in vitro. In osteoarthritis, the early osteochondral plate angiogenesis may further enhance the ability of microbiota to locate close to the deeper layers of cartilage, and this might lead to focal dysbiosis, low-grade inflammation, cartilage degradation, epigenetic changes in chondrocytes and worsening of osteoarthritis. More studies on cartilage across different ethnic groups, weights, and according to age, are needed, to confirm the silent presence of gut microbiota close to human cartilage and better understand its physiologic and pathogenic significance.

Metabolic cost adaptations during training with a soft exosuit assisting the hip joint.

Different adaptation rates have been reported in studies involving ankle exoskeletons designed to reduce the metabolic cost of their wearers. This work aimed to investigate energetic adaptations occurring over multiple training sessions, while walking with a soft exosuit assisting the hip joint. The participants attended five training sessions within 20 days. They walked carrying a load of 20.4 kg for 20 minutes with the exosuit powered and five minutes with the exosuit unpowered. Percentage change in net metabolic cost between the powered and unpowered conditions improved across sessions from -6.2 ± 3.9% (session one) to -10.3 ± 4.7% (session five), indicating a significant effect associated with training. The percentage change at session three (-10.5 ± 4.5%) was similar to the percentage change at session five, indicating that two 20-minute sessions may be sufficient for users to fully adapt and maximize the metabolic benefit provided by the exoskeleton. Retention was also tested measuring the metabolic reduction five months after the last training session. The percent change in metabolic cost during this session (-10.1 ± 3.2%) was similar to the last training session, indicating that the adaptations resulting in reduced metabolic cost are preserved. These outcomes are relevant when evaluating exoskeletons' performance on naïve users, with a specific focus on hip extension assistance.

Ultrasound and clinical features of hip involvement in patients with gout.

OBJECTIVES: To investigate the prevalence of the ultrasound findings indicative of monosodium urate crystal deposits at the hip joint in patients with gout and to explore the association between the ultrasound findings and the clinical and serological features. METHODS: Bilateral ultrasound assessment of the hip joint was carried out in 40 consecutive patients with gout, diagnosed according to the latest Gout American College of Rheumatology/European League Against Rheumatism classification criteria, and 25 disease controls. Ultrasound evidence of crystal deposits was obtained using the Outcome Measures in Rheumatology definitions: hip intra-articular aggregates and/or tophi, and "double contour" sign over the hyaline cartilage of the femoral head. RESULTS: The ultrasound examination revealed crystal deposits in at least one hip in 17 out of 40 patients (42.5%) with gout, and in 2 out of 25 disease controls (8.0%) (P = 0.0029). Aggregates, tophi, and "double contour" sign were found in at least one hip in 13 (32.5%), 6 (15.0%) and 6 (15.0%) out of 40 patients with gout, respectively. A moderate association between disease duration (P = 0.004, Rpb = 0.442), number of gouty "attacks" in the previous year (P = 0.029, Rpb = 0.346), presence of subcutaneous tophi (P = 0.037, V = 0.330) and ultrasound crystal deposits was found. CONCLUSION: Our results indicate that detecting monosodium urate crystals by ultrasound is common at hip joint in patients with gout.

A LINC00341-mediated regulatory pathway supports chondrocyte survival and may prevent osteoarthritis progression.

Osteoarthritis (OA) is the most common degenerative joint disease and results from progressive loss and destruction of articular cartilage and the underlying bone. The disease affects millions of people worldwide with an associated risk of mobility disability. However, the molecular basis underlying OA initiation and progression is not well understood and, currently, there is no effective intervention available to decelerate disease progression or restore degraded cartilage. We have found that lncRNA long intergenic nonprotein coding RNA 341 (LINC00341) is aberrantly downregulated in OA patient tissues and cultured OA chondrocytes. This is likely responsible for the increased apoptosis of chondrocytes and pathological destruction of cartilage. Further investigation has revealed that LINC00341 interacts with miR-141 to suppress its functional binding to the 3'-untranslated region of YY1-associated factor 2 (YAF2) messenger RNA. Aberrant downregulation of LINC00341 thus may ultimately lead to inhibition of the YAF2 protein, which has been implicated to be an antiapoptotic factor. Our study has revealed a new noncoding RNA-mediated regulatory network that highly likely protects chondrocytes by preventing apoptosis under normal conditions. The results will help further explore the molecular details pertaining to the progression of OA and stimulate efforts to develop effective therapies.

Hip Involvement in Patients With Calcium Pyrophosphate Deposition Disease: Potential and Limits of Musculoskeletal Ultrasound.

OBJECTIVE: To preliminarily explore the diagnostic potential of ultrasound (US) in detecting calcium pyrophosphate (CPP) crystal deposits at the hip joint in a cohort of patients with CPP deposition disease (CPPD) who were previously evaluated by conventional radiography (CR) and to assess the sensitivity and specificity as well as the agreement between US and CR in the evaluation of hip CPP crystal deposits. METHODS: Fifty consecutive patients with definite CPPD and 40 age/sex/body mass index-matched disease control subjects who had undergone hip CR within the previous 6 months were enrolled. Bilateral hip US examination was carried out to assess the presence of CCP crystal deposits at the acetabular labrum fibrocartilage and at the femoral head's hyaline cartilage. Two independent radiologists evaluated the presence of hip CPP crystal deposits on CR in both groups. RESULTS: US findings indicative of CPP crystal deposits were found in at least 1 hip in 45 of 50 patients with CPPD (90.0%) and in 73 of 100 hips (73.0%). CPP crystal deposits were more frequently found at the acetabular labrum fibrocartilage than at the femoral head's hyaline cartilage (72% and 17% of the hips in patients with CPPD, respectively). US and CR sensitivity was 90% and 86%, whereas US and CR specificity was 85% and 90%, respectively. Total agreement between the US and CR findings was 77.8%. CONCLUSION: Our results provide new evidence supporting US as a first-line, sensitive, safe, and reliable imaging technique in detecting CPP crystal deposits at the hip level.

Gene expression in hip soft tissues in incipient canine hip dysplasia and osteoarthritis.

Canine hip dysplasia and developmental dysplasia of the human hip share demographic, phenotypic, and clinical features including the predisposition to develop osteoarthritis in affected joints. To support the results of genetic mapping studies for CHD and its concomitant osteoarthritis with functional information, we performed RNA-seq on hip capsule and teres ligament of affected and unaffected dogs. RNA seq showed that expressed genes segregated according age, capsule or ligament, and hip phenotype. Expression of HHIP, DACT2, and WIF1 was significantly higher in capsule from control hips than dysplastic hips indicating a disruption of the hedgehog signaling pathway. Expression of SPON 1, a key component of the WNT pathway, was increased significantly in both dysplastic capsule and ligament while FBN2 and EMILIN3 were significantly increased in dysplastic capsule. Of genes associated with human hip osteoarthritis, expression of ACAN, IGF1, CILP2, COL11A1, COL8A1, and HAPLN was increased significantly in dysplastic capsule. The significant increase in expression of PLA2F, TNFRSF, TMEM, and IGFBP in dysplastic capsule indicated an injury response. Gene set enrichment analysis revealed that genes involved in extracellular matrix structure, epithelial to mesenchymal transition, myogenesis, growth factor signaling, cancer and immune pathways were enriched in dysplastic capsule. For teres ligament from dysplastic joints, genes in retinoic signaling pathways and those encoding extracellular matrix molecules, but not proteoglycans, were enriched. Hip tissues respond to abnormal mechanics early in dysplastic hip development and these pathways present targets for intervention in the early synovitis and capsulitis secondary to canine and human hip dysplasia. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:313-324, 2019.

Spread of injectate around hip articular sensory branches of the femoral nerve in cadavers.

BACKGROUND: Anatomical knowledge dictates that regional anaesthesia after total hip arthroplasty requires blockade of the hip articular branches of the femoral and obturator nerves. A direct femoral nerve block increases the risk of fall and impedes mobilisation. We propose a selective nerve block of the hip articular branches of the femoral nerve by an ultrasound-guided injection in the plane between the iliopsoas muscle and the iliofemoral ligament (the iliopsoas plane). The aim of this study was to assess whether dye injected in the iliopsoas plane spreads to all hip articular branches of the femoral nerve. METHODS: Fifteen cadaver sides were injected with 5 mL dye in the iliopsoas plane guided by ultrasound. Dissection was performed to verify the spread of injectate around the hip articular branches of the femoral nerve. RESULTS: In 10 dissections (67% [95% confidence interval: 38-88%]), the injectate was contained in the iliopsoas plane staining all hip articular branches of the femoral nerve without spread to motor branches. In four dissections (27% [8-55%]), the injection was unintentionally made within the iliopectineal bursa resulting in secondary spread. In one dissection (7% [0.2-32%]) adhesions partially obstructed the spread of dye. CONCLUSION: An injection of 5 mL in the iliopsoas plane spreads around all hip articular branches of the femoral nerve in 10 of 15 cadaver sides. If these findings translate to living humans, injection of local anaesthetic into the iliopsoas plane could generate a selective sensory nerve block of the articular branches of the femoral nerve without motor blockade.

Hip Synovial Fluid Cell Counts in Children From a Lyme Disease Endemic Area.

BACKGROUND: Patients with septic hip arthritis require surgical drainage, but they can be difficult to distinguish from patients with Lyme arthritis. The ability of synovial fluid white blood cell (WBC) counts to help discriminate between septic and Lyme arthritis of the hip has not been investigated. METHODS: We assembled a retrospective cohort of patients ≤21 years of age with hip monoarticular arthritis and a synovial fluid culture obtained who presented to 1 of 3 emergency departments located in Lyme disease endemic areas. Septic arthritis was defined as a positive synovial fluid culture result or synovial fluid pleocytosis (WBC count ≥50 000 cells per µL) with a positive blood culture result. Lyme arthritis was defined as positive 2-tiered Lyme disease serology results and negative synovial fluid bacterial culture results. All other patients were classified as having other arthritis. We compared median synovial fluid WBC counts by arthritis type. RESULTS: Of the 238 eligible patients, 26 (11%) had septic arthritis, 32 (13%) had Lyme arthritis, and 180 (76%) had other arthritis. Patients with septic arthritis had a higher median synovial fluid WBC count (126 130 cells per µL; interquartile range 83 303-209 332 cells per µL) than patients with Lyme arthritis (53 955 cells per µL; interquartile range 33 789-73 375 cells per µL). Eighteen patients (56%) with Lyme arthritis had synovial fluid WBC counts ≥50 000 cells per µL. Of the 94 patients who underwent surgical drainage, 13 were later diagnosed with Lyme arthritis. CONCLUSIONS: In Lyme disease endemic areas, synovial fluid WBC counts cannot always help differentiate septic from Lyme arthritis. Rapid Lyme diagnostics could help avoid unnecessary operative procedures in patients with Lyme arthritis.

A case report of basic calcium phosphate deposition disease mimicking septic arthritis.

We report a case of a 53-year-old man who presented with a diagnostic dilemma mimicking septic arthritis. It is important to consider the diagnosis of calcific peri-arthritis clinically and recognize the hallmarks on radiograph and magnetic resonance imaging as this disease process resolves completely with conservative management like in our patient, and does not require operative intervention.

Analysis of bearing wear, whole blood and synovial fluid metal ion concentrations and histopathological findings in patients with failed ASR hip resurfacings.

BACKGROUND: Adverse Reaction to Metal Debris (ARMD) is still a major reason for revision surgeries in patients with metal-on-metal (MoM) hip replacements. ARMD consists of a wide range of alterations in periprosthetic tissues, most important of which are metallosis, inflammation, pseudotumors and necrosis. Studies investigating histopathological findings and their association to implant wear or indirect measures of wear have yielded inconsistent results. Therefore, we aimed to investigate bearing surface wear volume, whole blood and synovial fluid metal ion concentrations, histopathological findings in periprosthetic tissues and their associations. METHODS: Seventy-eight patients with 85 hips revised for ARMD were included in the study. Prior to revision surgery, all patients had whole blood chromium and cobalt ion levels assessed. In revision surgery, a synovial fluid sample was taken and analyzed for chromium and cobalt. Periprosthetic tissue samples were taken and analyzed for histopathological findings. Explanted implants were analyzed for bearing wear volume of both acetabular cup and femoral head components. RESULTS: Volumetric wear of the failed components was highly variable. The total wear volume of the head and cup had a strong correlation with whole blood chromium and cobalt ion concentrations (Cr: ρ = 0.80, p < 0.001 and Co: ρ = 0.84, p < 0.001) and a bit weaker correlation with fluid chromium and cobalt ion concentrations (Cr: ρ = 0.50, p < 0.01 and Co: ρ = 0.41, p = 0.027). Most tissues displayed only low-to-moderate amounts of macrophages and lymphocytes. Total wear volume correlated with macrophage sheet thickness (ρ = 0.25, p = 0.020) and necrosis (ρ = 0.35, p < 0.01). Whole blood chromium and cobalt ion concentrations had similar correlations. Lymphocyte cuff thickness did not correlate with either total wear volume or whole blood metal ion concentrations, but correlated with the grade of necrosis. CONCLUSIONS: Bearing wear volume correlated with blood metal ion levels and the degree of necrosis and macrophage infiltration in periprosthetic tissues suggesting a dose-response relationship. Whole blood metal ion levels are a useful tool for clinician to estimate bearing wear and subsequent tissue response.