Combination of cobalt, chromium and titanium nanoparticles increases cytotoxicity in vitro and pro-inflammatory cytokines in vivo.

Background: The mixture of different metallic nanoparticles released from intended and unintended wearing of orthopaedic implants such as the Co/Cr cup and head, Co/Cr sleeves or tapers and their interface with Ti stems in the case of hip prostheses are a leading cause of adverse inflammatory responses and cytotoxicity to the host. Methods: This study assessed the in vitro cytotoxic effects of three metallic nanoparticles (Co, Cr and Ti) separately and in combination on macrophages. The in vivo effects were also evaluated after peri-tibial soft tissue injection in mice. Results: The results demonstrated that Co, Cr, and Ti nanoparticles and their combination were phagocytosed by macrophages both in vitro and in vivo. High doses of nanoparticles from each individual metal caused a variable rate of cell death in vitro. However, the mixture of Co/Cr/Ti nanoparticles was more toxic than the Co, Cr or Ti metals alone at low doses. Intracellular distribution of Co, Cr, and Ti in the combined group was heterogeneous and associated with distinct morphological features. The results from in vivo experiments showed a significant increase in the mRNA levels of interleukin (IL)-1ß, IL-6, IL-8 and tumour necrosis factor (TNF)-α in peri-tibial soft tissue following the administration of Co alone as well as the combination of nanoparticles. Conclusion: This study demonstrated that the combination of Co/Cr/Ti nanoparticles was more cytotoxic than any of the individual metals in vitro and induced higher expression of genes encoding pro-inflammatory cytokines than single metals in vivo. The in vivo model utilised in this study might provide a useful tool for rapid assessment of the effects of unintended release of metal nanoparticles from implants in pre-/post-marketing studies. Translational potential of this article: This study highlights the importance of preclinical assessments of potential nanoparticles produced by wear and tear of metal implants using macrophages and animal models, in particular their combinational toxicity in addition to the assessments of the bulk metallic materials.

PDIA3 epitope-driven immune autoreactivity contributes to hepatic damage in type 2 diabetes.

A diet rich in saturated fat and carbohydrates causes low-grade chronic inflammation in several organs, including the liver, ultimately driving nonalcoholic steatohepatitis. In this setting, environment-driven lipotoxicity and glucotoxicity induce liver damage, which promotes dendritic cell activation and generates a major histocompatibility complex class II (MHC-II) immunopeptidome enriched with peptides derived from proteins involved in cellular metabolism, oxidative phosphorylation, and the stress responses. Here, we demonstrated that lipotoxicity and glucotoxicity, as driven by a high-fat and high-fructose (HFHF) diet, promoted MHC-II presentation of nested T and B cell epitopes from protein disulfide isomerase family A member 3 (PDIA3), which is involved in immunogenic cell death. Increased MHC-II presentation of PDIA3 peptides was associated with antigen-specific proliferation of hepatic CD4+ immune infiltrates and isotype switch of anti-PDIA3 antibodies from IgM to IgG3, indicative of cellular and humoral PDIA3 autoreactivity. Passive transfer of PDIA3-specific T cells or PDIA3-specific antibodies also exacerbated hepatocyte death, as determined by increased hepatic transaminases detected in the sera of mice subjected to an HFHF but not control diet. Increased humoral responses to PDIA3 were also observed in patients with chronic inflammatory liver conditions, including autoimmune hepatitis, primary biliary cholangitis, and type 2 diabetes. Together, our data indicated that metabolic insults caused by an HFHF diet elicited liver damage and promoted pathogenic immune autoreactivity driven by T and B cell PDIA3 epitopes.

Synchrotron-based characterization of arthroprosthetic CoCrMo particles in human bone marrow.

Particles released from cobalt-chromium-molybdenum (CoCrMo) alloys are considered common elicitors of chronic inflammatory adverse effects. There is a lack of data demonstrating particle numbers, size distribution and elemental composition of bone marrow resident particles which would allow for implementation of clinically relevant test strategies in bone marrow models at different degrees of exposure. The aim of this study was to investigate metal particle exposure in human periprosthetic bone marrow of three types of arthroplasty implants. Periprosthetic bone marrow sections from eight patients exposed to CoCrMo particles were analyzed via spatially resolved and synchrotron-based nanoscopic X-ray fluorescence imaging. These analyses revealed lognormal particle size distribution patterns predominantly towards the nanoscale. Analyses of particle numbers and normalization to bone marrow volume and bone marrow cell number indicated particle concentrations of up to 1 × 1011 particles/ml bone marrow or 2 × 104 particles/bone marrow cell, respectively. Analyses of elemental ratios of CoCrMo particles showed that particularly the particles' Co content depends on particle size. The obtained data point towards Co release from arthroprosthetic particles in the course of dealloying and degradation processes of larger particles within periprosthetic bone marrow. This is the first study providing data based on metal particle analyses to be used for future in vitro and in vivo studies of possible toxic effects in human bone marrow following exposure to arthroprosthetic CoCrMo particles of different concentration, size, and elemental composition. Graphical abstract.

The contribution of the histopathological examination to the diagnosis of adverse local tissue reactions in arthroplasty.

The histopathological examination of the periprosthetic soft tissue and bone has contributed to the identification and description of the morphological features of adverse local tissue reactions (ALTR)/adverse reactions to metallic debris (ARMD). The need of a uniform vocabulary for all disciplines involved in the diagnosis and management of ALTR/ARMD and of clarification of the parameters used in the semi-quantitative scoring systems for their classification has been considered a pre-requisite for a meaningful interdisciplinary evaluation.This review of key terms used for ALTR/ARMD has resulted in the following outcomes: (a) pseudotumor is a descriptive term for ALTR/ARMD, classifiable in two main types according to its cellular composition defining its clinical course; (b) the substitution of the term metallosis with presence of metallic wear debris, since it cannot be used as a category of implant failure or histological diagnosis; (c) the term aseptic lymphocytic-dominated vasculitis- associated lesion (ALVAL) should be replaced due to the absence of a vasculitis with ALLTR/ALRMD for lymphocytic-predominant and AMLTR/AMRMD for macrophage-predominant reaction.This review of the histopathological classifications of ALTR/ARMD has resulted in the following outcomes: (a) distinction between cell death and tissue necrosis; (b) the association of corrosion metallic debris with adverse local lymphocytic reaction and tissue necrosis; (c) the importance of cell and particle debris for the viscosity and density of the lubricating synovial fluid; (d) a consensus classification of lymphocytic infiltrate in soft tissue and bone marrow; (e) evaluation of the macrophage infiltrate in soft tissues and bone marrow; (f) classification of macrophage induced osteolysis/aseptic loosening as a delayed type of ALTR/ARMD; (g) macrophage motility and migration as possible driving factor for osteolysis; (h) usefulness of the histopathological examination for the natural history of the adverse reactions, radiological correlation, post-marketing surveillance, and implant registries.The review of key terms used for the description and histopathological classification of ALTR/ARMD has resulted in a comprehensive, new standard for all disciplines involved in their diagnosis, clinical management, and long-term clinical follow-up. Cite this article: EFORT Open Rev 2021;6:399-419. DOI: 10.1302/2058-5241.6.210013.

The Disappearing Phalanx: A Case Report of a Vascular Tumor of the Toe.

We report a unique case of an epithelioid hemangioma of the third middle phalanx in which the lesion replaced the phalanx, became symptomatic, and then required resection, bone grafting, and joint arthroplasty. To the best of our knowledge, this is the first report of an epithelioid hemangioma in the toe that was treated using this approach.

Radiological and histological analysis of two replaced interphalangeal joints with active subchondral bone resorption in erosive hand osteoarthritis: a novel mechanism?

The aim of this study was to describe the histological features of erosive hand osteoarthritis (EHOA), which is considered an aggressive subset of hand osteoarthritis (OA) characterized by severe local inflammation and degeneration of the distal and proximal interphalangeal joints. Two patients with EHOA underwent replacement with a cement-free press fit ceramic prosthesis of a proximal interphalangeal joint (PIPJ). Clinical and radiological data were collected and histological examination was performed. Radiological examination with histological correlation showed complete erosion of the articular cartilage with focal presence of peripheral fibrocartilaginous resurfacing, sclerosis, and remodeling of the exposed bone, osteoclastic activity with resorptive lacunae in the subchondral bone and around degenerative fibromyxoid pseudocysts, coarse trabeculation of the cancellous bone, and marginal osteophytes. The synovial membrane showed non-specific mild hypertrophy and mildly cellular fibromyxoid stroma. The histological findings in patients with EHOA suggest a pathogenesis of cartilage resorption from the subchondral bone, via osteoclastic-mediated activity and formation of periarticular reactive fibrocartilaginous proliferation with partial resurfacing of the articular surface.

Valgus Stress Radiographs Predict Lateral-Compartment Cartilage Thickness but Not Cartilage Degeneration in Varus Osteoarthritis.

BACKGROUND: Intact cartilage in the lateral compartment is an important requirement for medial unicompartmental knee arthroplasty. This study sought to determine how measurements of joint space width in the lateral compartment on valgus stress radiographs compare to cartilage thickness as measured with a precise needle test, and whether cartilage thickness is a predictor of cartilage degeneration. METHODS: A consecutive series of 100 knees undergoing total knee arthroplasty for end-stage varus osteoarthritis was studied. Twenty-eight knees were retrospectively excluded because not all data were available, leaving 72 knees (61 patients; mean age, 67 years [49-87]). On calibrated valgus stress radiographs, lateral-compartment joint space width was measured. During surgery, osteochondral samples of the distal lateral femur and the lateral tibia plateau were harvested. Cartilage thickness and histology were assessed. Cartilage thickness of tibia and femur was defined as lateral-compartment cartilage thickness. RESULTS: Lateral-compartment joint space width on valgus stress radiographs and lateral-compartment cartilage thickness correlated well (rs = 0.671, P < .001). However, no correlation of cartilage histology according to the osteoarthritis cartilage histopathology assessment system, and cartilage thickness on the lateral tibia plateau (rs = -0.060, P = .614) and cartilage thickness on the distal lateral femur (rs = -0.128, P = .282) was observed. CONCLUSION: Valgus stress radiographs can assess combined cartilage thickness in the lateral compartment of the knee. Cartilage thickness, however, is a poor predictor of cartilage degeneration.

Non-Lethal Type VIII Osteogenesis Imperfecta Has Elevated Bone Matrix Mineralization.

CONTEXT: Type VIII osteogenesis imperfecta (OI; OMIM 601915) is a recessive form of lethal or severe OI caused by null mutations in P3H1, which encodes prolyl 3-hydroxylase 1. OBJECTIVES: Clinical and bone material description of non-lethal type VIII OI. DESIGN: Natural history study of type VIII OI. SETTING: Pediatric academic research centers. PATIENTS: Five patients with non-lethal type VIII OI, and one patient with lethal type VIII OI. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Clinical examinations included bone mineral density, radiographs, and serum and urinary metabolites. Bone biopsy samples were analyzed for histomorphometry and bone mineral density distribution by quantitative backscattered electron imaging microscopy. Collagen biochemistry was examined by mass spectrometry, and collagen fibrils were examined by transmission electron microscopy. RESULTS: Type VIII OI patients have extreme growth deficiency, an L1-L4 areal bone mineral density Z-score of -5 to -6, and normal bone formation markers. Collagen from bone and skin tissue and cultured osteoblasts and fibroblasts have nearly absent 3-hydroxylation (1-4%). Collagen fibrils showed abnormal diameters and irregular borders. Bone histomorphometry revealed decreased cortical width and very thin trabeculae with patches of increased osteoid, although the overall osteoid surface was normal. Quantitative backscattered electron imaging showed increased matrix mineralization of cortical and trabecular bone, typical of other OI types. However, the proportion of bone with low mineralization was increased in type VIII OI bone, compared to type VII OI. CONCLUSIONS: P3H1 is the unique enzyme responsible for collagen 3-hydroxylation in skin and bone. Bone from non-lethal type VIII OI children is similar to type VII, especially bone matrix hypermineralization, but it has distinctive features including extremely thin trabeculae, focal osteoid accumulation, and an increased proportion of low mineralized bone.

Histopathological characterization of corrosion product associated adverse local tissue reaction in hip implants: a study of 285 cases.

BACKGROUND: Adverse local tissue reaction (ALTR), characterized by a heterogeneous cellular inflammatory infiltrate and the presence of corrosion products in the periprosthetic soft tissues, has been recognized as a mechanism of failure in total hip replacement (THA). Different histological subtypes may have unique needs for longitudinal clinical follow-up and complication rates after revision arthroplasty. The purpose of this study was to describe the histological patterns observed in the periprosthetic tissue of failed THA in three different implant classes due to ALTR and their association with clinical features of implant failure. METHODS: Consecutive patients presenting with ALTR from three major hip implant classes (N = 285 cases) were identified from our prospective Osteolysis Tissue Database and Repository. Clinical characteristics including age, sex, BMI, length of implantation, and serum metal ion levels were recorded. Retrieved synovial tissue morphology was graded using light microscopy. Clinical characteristics and features of synovial tissue analysis were compared between the three implant classes. Histological patterns of ALTR identified from our observations and the literature were used to classify each case. The association between implant class and histological patterns was compared. RESULTS: Our histological analysis demonstrates that ALTR encompasses three main histological patterns: 1) macrophage predominant, 2) mixed lymphocytic and macrophagic with or without features of associated with hypersensitivity/allergy or response to particle toxicity (eosinophils/mast cells and/or lymphocytic germinal centers), and 3) predominant sarcoid-like granulomas. Implant classification was associated with histological pattern of failure, and the macrophagic predominant pattern was more common in implants with metal-on-metal bearing surfaces (MoM HRA and MoM LHTHA groups). Duration of implantation and composition of periprosthetic cellular infiltrates was significantly different amongst the three implant types examined suggesting that histopathological features of ALTR may explain the variability of clinical implant performance in these cases. CONCLUSIONS: ALTR encompasses a diverse range of histological patterns, which are reflective of both the implant configuration independent of manufacturer and clinical features such as duration of implantation. The macrophagic predominant pattern and its mechanism of implant failure represent an important subgroup of ALTR which could become more prominent with increased length of implantation.

Prevention of Defective Placentation and Pregnancy Loss by Blocking Innate Immune Pathways in a Syngeneic Model of Placental Insufficiency.

Defective placentation and subsequent placental insufficiency lead to maternal and fetal adverse pregnancy outcome, but their pathologic mechanisms are unclear, and treatment remains elusive. The mildly hypertensive BPH/5 mouse recapitulates many features of human adverse pregnancy outcome, with pregnancies characterized by fetal loss, growth restriction, abnormal placental development, and defects in maternal decidual arteries. Using this model, we show that recruitment of neutrophils triggered by complement activation at the maternal/fetal interface leads to elevation in local TNF-α levels, reduction of the essential angiogenic factor vascular endothelial growth factor, and, ultimately, abnormal placentation and fetal death. Blockade of complement with inhibitors specifically targeted to sites of complement activation, depletion of neutrophils, or blockade of TNF-α improves spiral artery remodeling and rescues pregnancies. These data underscore the importance of innate immune system activation in the pathogenesis of placental insufficiency and identify novel methods for treatment of pregnancy loss mediated by abnormal placentation.

Glomus Tumors in the Foot: Case Series.

UNLABELLED: Glomus tumors are painful, benign neoplasms that frequently are associated with delayed diagnosis. Commonly in the hand, they rarely present in the foot. The purpose of this case series is to characterize the clinical presentation, radiology, pathology, and surgical outcomes associated with foot glomus tumors. We reviewed our pathology database for patients with foot glomus tumors diagnosed between 1995 and 2013. Medical records including physician notes, pathology, and radiology were reviewed. Eleven patients had foot glomus tumors excised at our institution during the study period. The mean age was 45.4 (range = 28-60) years. One patient was lost to follow-up. Mean follow-up for the remaining 10 patients was 44.7 (range = 3-142) months. Ten tumors were located in the subungual region, while 1 was located in the plantar pulp of the distal phalanx. All patients presented with pain. Point tenderness, cold hypersensitivity, and nail abnormalities were variably documented but frequently present. Four patients had had prior surgery for an ingrown toenail prior to presentation at our institution. Six patients had preoperative magnetic resonance imaging studies, which were diagnostic of glomus tumor in all cases except one. Radiographs failed to provide diagnosis in all 8 patients for whom they were obtained. Postoperatively, all patients had complete symptom relief with no recurrences.In conclusion, this case series demonstrates that foot glomus tumors frequently present with classic symptoms including pain, point tenderness, and cold hypersensitivity. When clinically suspected, magnetic resonance imaging should be obtained. Marginal excision results in symptom relief and cure. LEVEL OF EVIDENCE: Therapeutic, Level IV: Case series.

Molecular analysis of chromium and cobalt-related toxicity.

Occupational and environmental exposure to Co and Cr has been previously linked to a wide array of inflammatory and degenerative conditions and cancer. Recently, significant health concerns have been raised by the high levels of Cr and Co ions and corrosion products released by biomedical implants. Herein, we set to analyze the biological responses associated with Co and Cr toxicity. Histological, ultrastructural, and elemental analysis, performed on Cr and Co exposed patients reveal the presence of corrosion products, metallic wear debris and metal ions at varying concentrations. Metallic ions and corrosion products were also generated in vitro following macrophage phagocytosis of metal alloys. Ex vivo redox proteomic mapped several oxidatively damaged proteins by Cr(III) and Co(II)-induced Fenton reaction. Importantly, a positive correlation between the tissue amounts of Cr(III) and Co(II) ions and tissue oxidative damage was observed. Immobilized- Cr(III) and Co(II) affinity chromatography indicated that metal ions can also directly bind to several metallo and non-metalloproteins and, as demonstrated for aldolase and catalase, induce loss of their biological function. Altogether, our analysis reveals several biological mechanisms leading to tissue damage, necrosis, and inflammation in patients with Cr and Co-associated adverse local tissue reactions.

Does intraarticular inflammation predict biomechanical cartilage properties?

BACKGROUND: Intact cartilage in the lateral compartment is an important requirement for medial unicompartmental knee arthroplasty (UKA). Progression of cartilage degeneration in the lateral compartment is a common failure mode of medial UKA. Little is known about factors that influence the mechanical properties of lateral compartment cartilage. QUESTIONS/PURPOSES: The purposes of this study were to answer the following questions: (1) Does the synovial fluid white blood cell count predict the biomechanical properties of macroscopically intact cartilage of the distal lateral femur? (2) Is there a correlation between MRI grading of synovitis and the biomechanical properties of macroscopically intact cartilage? (3) Is there a correlation between the histopathologic assessment of the synovium and the biomechanical properties of macroscopically intact cartilage? METHODS: The study included 84 patients (100 knees) undergoing primary TKA for varus osteoarthritis between May 2010 and January 2012. All patients underwent preoperative MRI to assess the degree of synovitis. During surgery, the cartilage of the distal lateral femur was assessed macroscopically using the Outerbridge grading scale. In knees with an Outerbridge grade of 0 or 1, osteochondral plugs were harvested from the distal lateral femur for biomechanical and histologic assessment. The synovial fluid was collected to determine the white blood cell count. Synovial tissue was taken for histologic evaluation of the degree of synovitis. RESULTS: The mean aggregate modulus and the mean dynamic modulus were significantly greater in knees with 150 or less white blood cells/mL synovial fluid compared with knees with greater than 150 white blood cells/mL synovial fluid. There was no correlation among MRI synovitis grades, histopathologic synovitis grades, and biomechanical cartilage properties. CONCLUSIONS: The study suggests that lateral compartment cartilage in patients with elevated synovial fluid white blood cell counts has a reduced ability to withstand compressive loads. LEVEL OF EVIDENCE: Level III, diagnostic study. See the Instructions for Authors for a complete description of levels of evidence.

Magnetic resonance imaging findings in symptomatic versus asymptomatic subjects following metal-on-metal hip resurfacing arthroplasty.

BACKGROUND: Although pseudotumors have been reported at the sites of well-functioning and painful metal-on-metal hip prostheses, there are no objective data on the magnitude of the adverse reaction. This observational study was performed to investigate the ability of modified magnetic resonance imaging (MRI) to detect and quantify adverse synovial responses in symptomatic and asymptomatic subjects following metal-on-metal hip resurfacing. We hypothesized that the magnitude of the synovial reactions would be greater in symptomatic patients. METHODS: Sixty-nine patients (seventy-four hips) with hip resurfacing were divided into three groups: asymptomatic (twenty-two hips), symptomatic with a mechanical cause (twenty), and unexplained pain (thirty-two). The volume of synovitis was calculated on MRI for all patients. RESULTS: Synovitis was detected in fifteen asymptomatic hips (68%), fifteen (75%) with symptoms with a mechanical causes, and twenty-five (78%) with unexplained pain. The mean volume (and standard deviation) of the synovitis in these groups was 5 ± 7 cm³, 10 ± 16 cm³, and 31 ± 47 cm³, respectively. The coefficient of repeatability between the examiners was 1.8 cm³ for measurement of synovitis. Of the thirteen subjects with revision arthroplasty, six had an adverse local tissue reaction. This subgroup had the highest volumes of synovitis on MRI. CONCLUSIONS: An adverse synovial reaction was detected on MRI in both symptomatic and asymptomatic subjects. We found a larger volume of synovitis in symptomatic patients; this increase reached significance only in the group with an adverse local tissue reaction. Synovial volume on MRI may be a valuable marker in the longitudinal assessment of asymptomatic patients with a metal-on-metal hip resurfacing and in identifying patients with adverse local tissue reaction.

MRI findings in painful metal-on-metal hip arthroplasty.

OBJECTIVE: The objective of our study was to compare the frequency of osseous and soft-tissue abnormalities in patients presenting with hip pain after resurfacing arthroplasty and after total hip arthroplasty (THA), correlate the MRI findings with histologic results, and determine which MRI findings are predictive of aseptic lymphocytic vasculitis-associated lesions. MATERIALS AND METHODS: The MRI examinations of patients with metal-on-metal hip prostheses placed at resurfacing arthroplasty (n=31) or THA (n=29) were reviewed for osteolysis, synovitis, extracapsular disease, synovial pattern, and mode of decompression into adjacent bursae. Regional muscles and tendons were assessed for tendinosis, tear, atrophy, and edema. Histologic and operative findings were reviewed in 19 patients (20 hips) who underwent revision surgery. Chi-square tests were performed to detect differences between the resurfacing arthroplasty and THA groups. The Wilcoxon rank sum test was performed to detect differences in MRI findings in patients with and those without aseptic lymphocytic vasculitis-associated lesions. RESULTS: Synovitis was detected in 77.4% of resurfacing arthroplasty hips and 86.2% of THA hips. Extracapsular disease was present in 6.5% of resurfacing arthroplasty hips and 10.3% of THA hips. Osteolysis was detected in 9.7% of resurfacing arthroplasty hips and 24.1% of THA hips. There was no difference in the incidence of synovitis (p=0.51), osteolysis (p=0.17), or extracapsular disease (p=0.67) between the resurfacing arthroplasty and THA groups. Patients with aseptic lymphocytic vasculitis-associated lesions had higher volumes of synovitis (p=0.04) than patients without aseptic lymphocytic vasculitis-associated lesions. Extracapsular disease and muscle edema were seen only in patients with aseptic lymphocytic vasculitis-associated lesions. CONCLUSION: Synovitis is common in patients with metal-on-metal hip prostheses and occurs with a similar incidence after resurfacing arthroplasty and after THA; osteolysis and extracapsular disease are uncommon. The MRI signs most suggestive of aseptic lymphocytic vasculitis-associated lesions are high volumes of synovitis, extracapsular disease, and intramuscular edema.

Multimodality treatment of a multifocal osteoblastoma-like tumor of the lower extremity.

Osteoblastoma-like tumor is a rare condition with limited information on its orthopedic management in the current medical literature. The tumor histologically resembles an osteoblastoma, although the radiographic features are similar to those observed in primary vascular lesions. The treatment in the previously reported cases involved aggressive procedures including amputation, en bloc resection, and chemotherapy because of the uncertainty regarding the biological behavior of the tumor. We present a case of this entity that was successfully treated by a combination therapy including intralesional curettage with adjuvant cryotherapy, in situ and intravenous administration of bisphosphonates and radioablation.

Leiomyoma of the foot: sonographic features with pathologic correlation.

Leiomyomas arising outside of the uterus and gastrointestinal tract are uncommon, though these benign soft tissue neoplasms have been reported in the lower extremity and foot. To our knowledge, the sonographic appearance of a lower extremity leiomyoma has not been described in the literature. This report involves a case of leiomyoma of the foot and its sonographic imaging features. MR correlative imaging and histopathology are also provided.

Proliferative lesions and metalloproteinase activity in murine lupus nephritis mediated by type I interferons and macrophages.

Glomerulonephritis is a major cause of morbidity in patients with systemic lupus erythematosus. Although substantial progress has been made in the identification of pathogenic triggers that result in autoantibody production, little is known about the pathogenesis of aggressive proliferative processes that lead directly to irreversible glomerular damage and compromise of renal function. In this study, we describe a model of polyinosinic: polycytidylic acid-accelerated lupus nephritis in NZB/W mice that is characterized by severe glomerular proliferative lesions with de novo crescent formation, findings that are linked with decreased survival and adverse outcomes in lupus. Proliferative glomerulonephritis was associated with infiltrating kidney macrophages and renal expression of IFN-inducible genes, matrix metalloproteinases (MMPs), and growth factors. Crescent formation and renal MMP and growth factor expression were dependent on renal macrophages that expressed Il10, MMPs, osteopontin, and growth factors, including Pdgfc and Hbegf. Infiltrating macrophages and renal MMP expression were induced by type I IFN. These findings reveal a role for type I IFNs and alternatively activated macrophages in aggressive proliferative lesions of lupus nephritis.

Foreign body reaction to artelon spacer: case report.

Anecdotal reports of painful synovitis after implantation of the Artelon spacer (Small Bone Innovations, Inc., Morrisville, PA) have emerged. The manufacturer claims that this type of reaction is related to the method of fixation and/or to suture material. This report illustrates one case in which a patient exhibited sustained painful synovitis after implantation of the Artelon spacer in the scaphotrapezio-trapezoidal joint, which clinically resolved on removal of the implant. Furthermore, pathology specimens of the soft tissue, synovium, and bone demonstrated an exuberant granulomatous foreign body giant cell reaction to the implant material. Patients should be made aware of the potential of the Artelon spacer to cause a foreign body reaction that may necessitate reoperation for removal of the implant.