Increased Rate of Complications Following Total Knee Arthroplasty in Patients Who Have Polymyositis.

BACKGROUND: Polymyositis (PM) is a systemic connective tissue disorder that can lead to early onset degenerative joint disease and a need for total knee arthroplasty (TKA). Outcomes of TKA in patients who have PM are not well documented in the literature. The purpose of this study was to evaluate PM as a risk factor for complications after TKA. METHODS: Using a national private payer insurance database from 2010 to 2022, PM patients undergoing primary TKA were compared to 10:1 matched controls based on age, sex, and comorbidities. Multivariable logistic regression analyses were done for medical complications up to 90 days and surgical complications up to 2 years. 90-day emergency department visits and inpatient readmissions were also documented. A total of 25,039 patients undergoing primary TKA were queried, of which 2,290 had PM. RESULTS: Compared to the matched controls, patients who had PM demonstrated higher rates of medical and surgical complications, including pulmonary embolism (1.0% versus 0.5%, P = .001), cerebrovascular accident (1.3% versus 0.7%, P = .002), wound complications (3.4% versus 2.1%, P < .001), and periprosthetic joint infection at 1 year (1.7% versus 1.3%, P = .042) and 2 years (2.6% versus 1.9%, P = .006). Patients who had PM displayed elevated 90-day emergency department (14.9% versus 13.3%, P = .032) and hospital readmission rate (7.1% versus 4.8%, P < .001). CONCLUSIONS: Patients who have PM are at higher risks of postoperative medical and surgical complications, including pulmonary embolism, cerebrovascular accident, wound complication, and periprosthetic joint infection. Given these results, it is helpful for orthopedic surgeons and patients to consider these risks when considering TKA for patients who have PM.

Increased Rate of Complications Following Total Knee Arthroplasty in Patients Who Have Marfan Syndrome.

BACKGROUND: Outcomes of Marfan syndrome (MFS) patients after total knee arthroplasty (TKA) are poorly documented in the literature. The purpose of this study was to evaluate MFS as a potential risk factor for complications after TKA. METHODS: Using a national private payer insurance database from 2010 to 2022, MFS patients undergoing primary TKA were identified and compared to 10:1 matched controls based on age, sex, obesity, diabetes mellitus, and a comorbidity index. A total of 4,092 patients undergoing primary TKA were analyzed, of which 372 had MFS. Multivariable logistic regression analyses were done for medical complications up to 90 days and surgical complications up to 2 years. 90-day emergency department-visits and inpatient readmissions were also documented. RESULTS: Compared to the matched controls, patients who have MFS displayed elevated rates of surgical complications, including prosthetic instability (1-year, odds ratio (OR) 3.88, 95% confidence interval (CI) [1.58 to 8.66]; 2-year, OR 4.39, 95% CI [2.16 to 8.44]), and revision surgery (2 year, OR 1.79, 95% CI [1.05 to 2.91]). Additionally, patients who have MFS demonstrated significant higher rates of medical complications, including aortic dissection (2.15 versus 0%) and transfusion (OR 2.63, 95% CI [1.31 to 4.90]). CONCLUSIONS: Patients who have MFS are at higher risks of postoperative complications after TKA, encompassing both medical and surgical complications. Specifically, patients who have MFS have a significantly higher likelihood of experiencing prosthetic instability and requiring revision surgery. Given these results, it is crucial for orthopedic surgeons and patients alike to consider these risks when determining a course of TKA for patients who have MFS.

Effect of Patient Age on Total Hip Arthroplasty Outcomes in Patients Who Have Osteonecrosis of the Femoral Head Compared to Patients Who Have Hip Osteoarthritis.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) affects both young and old patients. However, outcomes following total hip arthroplasty (THA) for these patients may vary with age. This study aimed to examine the effect of age on THA outcomes for non-traumatic ONFH patients, an area currently lacking research. METHODS: Patients who had non-traumatic ONFH undergoing THA with at least 2 years of follow-up were identified using a database and divided into four groups by age. Then, 4 matched control groups of patients who had hip osteoarthritis (OA) were created. Multivariate logistic regression analyses were used to evaluate the rates of medical and surgical complications. Additionally, cohorts with a minimum 5-year follow-up were filtered to obtain further data on surgical outcomes. The study analyzed 85,462 non-traumatic ONFH and 80,120 hip OA patients undergoing THA. RESULTS: Multiple medical complications in ONFH patients increased with age. Periprosthetic fracture within 2 years increased with age, while 90-day wound complications, 2-year periprosthetic joint infections, dislocations, and revisions decreased. The trends for complications continued at the 5-year follow-up. Compared to OA patients, those who had ONFH had higher risks of most complications, but this discrepancy decreased with age. CONCLUSIONS: In ONFH patients undergoing THA, medical complications generally rise with age, while most surgical complications, including revisions, decrease. It is notable that ONFH patients experienced more complications than those who had OA, but this difference diminished with age.

Formyl peptide receptors in bone research.

PURPOSE/AIM OF THE STUDY: The formyl peptide receptor (FPR) participates in the immune response, with roles in infection and inflammation. In this review article, we summarize the current literature on these roles before discussing the function of FPRs in the pathogenesis of musculoskeletal disorders including osteoarthritis (OA), degenerative disc disease (DDD), and rheumatoid arthritis (RA). Additionally, we discuss the potential diagnostic and therapeutic roles of FPRs in these domains. METHODS: PubMed and Ovid MEDLINE searches were performed from 1965 through March 2022. Keywords included "FPR, tissue expression, inflammation, infection, musculoskeletal disorder, bone, rheumatoid arthritis, osteoarthritis, degenerative disc disease, mitochondria." RESULTS: Sixty-nine studies were included in this review article. FPRs appear to be ubiquitous in the pathogenesis, diagnosis, and treatment of common musculoskeletal disorders. They can potentially be utilized for the earlier diagnosis of OA and DDD. They may be employed with mesenchymal stem cells (MSCs) to reverse OA and DDD pathologies. With anti-inflammatory, anti-osteolytic, and pro-angiogenic functions, they may broaden treatment options in RA. CONCLUSIONS: FPRs appear to be heavily involved in the pathogenesis of common musculoskeletal conditions, including arthritis, degenerative disc disease, and rheumatoid arthritis. Furthermore, they demonstrate much promise in the diagnosis and treatment of these conditions. Their roles should continue to be explored.

Fewer Than One in 20 Current Academic Orthopaedic Surgeons Have Obtained National Institutes of Health Funding.

BACKGROUND: National Institutes of Health (NIH) funding is a key driver of orthopaedic research, but it has become increasingly difficult to obtain in recent years. An understanding of the types of grants that are commonly funded, how productive they are, and the factors associated with obtaining funding may help orthopaedic surgeons better understand how to earn grants. QUESTIONS/PURPOSES: In this study, we sought to determine (1) the proportion of current academic orthopaedic surgeons who have obtained NIH grant funding, (2) the productivity of these grants by calculating grant productivity metrics, and (3) the factors (such as gender, subspecialty, and additional degrees) that are associated with obtaining grant funding. METHODS: Current academic orthopaedic surgeons at the top 140 NIH-funded institutions were identified via faculty webpages; 3829 surgeons were identified. Demographic information including gender (men constituted 88% of the group [3364 of 3829]), academic rank (full professors constituted 22% [856 of 3829]), additional degrees (those with MD-PhD degrees constituted 3% [121 of 3829]), leadership positions, and orthopaedic subspecialty was collected. Funding histories from 1985 through 2021 were collected using the NIH Research Portfolio Online Reporting Tools Expenditures and Results. Grant type, funding, publications, and citations of each article were collected. A previously used grant impact metric (total citations per USD 0.1 million) was calculated to assess grant productivity. Multivariable binomial logistic regression was used to evaluate factors associated with obtaining funding. RESULTS: Four percent (150 of 3829) of academic orthopaedic surgeons obtained USD 338.3 million in funding across 301 grants, resulting in 2887 publications over the entire study period. The R01 was the most commonly awarded grant in terms of the total number awarded, at 36% (108 of 301), as well as by funding, publications, and citations, although other grant types including T32, F32, R03, R13, and R21 had higher mean grant impact metrics. There was no difference between men and women in the by-gender percentage of academic orthopaedic surgeons who obtained funding (4% [135 of 3229] versus 3% [15 of 450]; odds ratio 0.9 [95% confidence interval 0.5 to 1.7]; p = 0.80). A department having a single funded PhD researcher may be associated with surgeon-scientists obtaining grant funding, but with the numbers available, we could not demonstrate this was the case (OR 1.4 [95% CI 0.9 to 2.2]; p = 0.12). CONCLUSION: Fewer than one in 20 academic orthopaedic surgeons have received NIH funding. R01s are the most commonly awarded grant, although others demonstrate increased productivity metrics. Future studies should investigate the role of co-principal investigators on productivity and the role of different funding sources. CLINICAL RELEVANCE: Individuals should pursue both R01 and non-R01 grants, and departments should consider cultivating relationships with funded PhDs. The specific research infrastructure and departmental policies of the most productive institutions and grants should be surveyed and emulated.

Mobile health supported multi-domain recovery trajectories after major arthroplasty or spine surgery: a pilot feasibility and usability study.

BACKGROUND: Recovery after surgery intersects physical, psychological, and social domains. In this study we aim to assess the feasibility and usability of a mobile health application called PositiveTrends to track recovery in these domains amongst participants undergoing hip, knee arthroplasty or spine surgery. Our secondary aim was to generate procedure-specific, recovery trajectories within the pain and medication, psycho-social and patient-reported outcomes domain. METHODS: Prospective, observational study in participants greater than eighteen years of age. Data was collected prior to and up to one hundred and eighty days after completion of surgery within the three domains using PositiveTrends. Feasibility was assessed using participant response rates from the PositiveTrends app. Usability was assessed quantitatively using the System Usability Scale. Heat maps and effect plots were used to visualize multi-domain recovery trajectories. Generalized linear mixed effects models were used to estimate the change in the outcomes over time. RESULTS: Forty-two participants were enrolled over a four-month recruitment period. Proportion of app responses was highest for participants who underwent spine surgery (median = 78, range = 36-100), followed by those who underwent knee arthroplasty (median = 72, range = 12-100), and hip arthroplasty (median = 62, range = 12-98). System Usability Scale mean score was 82 ± 16 at 180 days postoperatively. Function improved by 8 and 6.4 points per month after hip and knee arthroplasty, respectively. In spine participants, the Oswestry Disability Index decreased by 1.4 points per month. Mood improved in all three cohorts, however stress levels remained elevated in spine participants. Pain decreased by 0.16 (95% Confidence Interval: 0.13-0.20, p < 0.001), 0.25 (95% CI: 0.21-0.28, p < 0.001) and 0.14 (95% CI: 0.12-0.15, p < 0.001) points per month in hip, knee, and spine cohorts respectively. There was a 10.9-to-40.3-fold increase in the probability of using no medication for each month postoperatively. CONCLUSIONS: In this study, we demonstrate the feasibility and usability of PositiveTrends, which can map and track multi-domain recovery trajectories after major arthroplasty or spine surgery.

Outcomes Following Total Hip Arthroplasty in Patients Who Have Charcot Neuroarthropathy of the Hip.

BACKGROUND: Historically, Charcot neuroarthropathy hip (CNH) was deemed a contraindication for total hip arthroplasty (THA). However, as implant design and surgical techniques advance, THA for CNH has been performed and documented in literature. Information regarding the outcomes of THA for CNH is limited. The objective of the study was to assess outcomes following THA in patients who have CNH. METHODS: Patients who have CNH underwent primary THA and had at least 2 years of follow-up were identified in a national insurance database. For comparison, a 1:10 matched control cohort of patients who did not have CNH was created based on age, sex, and relevant comorbidities. Eight hundred and ninety-five CNH patients who underwent primary THA were compared to 8,785 controls. Medical outcomes, emergency department visits, hospital readmissions, and surgical outcomes including revisions between cohorts were evaluated using multivariate logistic regressions. RESULTS: The CNH patients were found to have higher risks of 90-day wound complications (P = .014), periprosthetic joint infection (P = .013) (P = .021), dislocation (P < .001) (P < .001), aseptic loosening (P = .040) (P = .002), periprosthetic fracture (P = .003) (P < .001), and revision (P < .001) (P < .001) at 1-year and 2-year follow-up, respectively. CONCLUSION: While patients who have CNH are at a higher risk of wound and implant-related complications, they are comparatively lower than previously reported in literature. Orthopaedic surgeons should be cognizant of the increased risk in this population to provide appropriate preoperative counseling and enhanced perioperative medical management.

Risks Following Total Knee Arthroplasty in Patients Who Have Antiphospholipid Syndrome.

BACKGROUND: Antiphospholipid syndrome (APS) is recognized as a thrombophilic autoimmune condition characterized by a tendency to develop venous thromboembolism. Total knee arthroplasty (TKA) is a prevalent procedure in patients who have advanced knee arthritis. Notably, TKA is unequivocally considered a thrombotic risk factor. However, outcomes of APS patients after TKA are still poorly documented in literature. The purpose of this study was to evaluate APS as a potential risk factor for complications after TKA. METHODS: Using the PearlDiver Mariner database from 2010 to 2022, APS patients undergoing primary TKA were identified and compared to 10:1 matched control based on age, sex, and relevant comorbidities. A total of 7,478 patients undergoing primary TKA were analyzed, of which 683 had APS. Multivariable logistic regression analyses were done for medical complications up to 90 days and surgical complications including revision up to 2 years. Ninety-day emergency department visit and inpatient readmission were also documented. RESULTS: Within 90 days after TKA, patients who have APS exhibited higher rates of cerebrovascular accident (adjusted odds ratio 2.04, 95% confidence interval 1.12 to 3.57; P = .014) and deep vein thrombosis (adjusted odds ratio 2.87, 95% confidence interval 1.99 to 4.06; P < .001) as compared to matched controls. No difference in surgical or nonthrombotic medical complications was observed between 2 cohorts. CONCLUSIONS: There were significantly higher rates of stroke and deep vein thrombosis in APS patients. Our study did not find statistical differences in other surgical complications or readmissions between the 2 groups. Orthopaedic surgeons should consider appropriate prophylaxis of thrombosis in this patient population undergoing TKA perioperatively.

Outcomes Following Hemiarthroplasty for Femoral Neck Fracture in Patients Who Have Hemiparesis.

BACKGROUND: Hemiparesis increases the risk of femoral neck fracture (FNF) in the elderly, which frequently necessitates hemiarthroplasty. There are limited reports on the outcomes of hemiarthroplasty in patients who have hemiparesis. The purpose of this study was to evaluate hemiparesis as a potential risk factor for medical and surgical complications following hemiarthroplasty. METHODS: Hemiparetic patients who have concomitant FNF and underwent hemiarthroplasty with at least 2 years of follow-up were identified using a national insurance database. A 10:1 matched control cohort of patients who did not have hemiparesis was created for comparison. There were 1,340 patients who have and 12,988 patients who did not have hemiparesis undergoing hemiarthroplasty for FNF. Multivariate logistic regression analyses were used to evaluate rates of medical and surgical complications between the 2 cohorts. RESULTS: Aside from increased rates of medical complications including cerebrovascular accident (P < .001), urinary tract infection (P = .020), sepsis (P = .002), and myocardial infarction (P < .001), patients who have hemiparesis also experienced higher rates of dislocation within 1 and 2 years (Odds Ratio (OR) 1.54, P = .009; OR 1.52, P = .010). Hemiparesis was not associated with higher risk of wound complications, periprosthetic joint infection, aseptic loosening, and periprosthetic fracture, but was associated with higher incidence of 90-day ED-visits (OR 1.16, P = .031) and 90-day readmission (OR 1.32, P < .001). CONCLUSION: While patients who have hemiparesis do not have increased risk of implant-related complications other than dislocation, they are at increased risk of developing medical complications following hemiarthroplasty for FNF.

Increased rate of complications following total knee arthroplasty in patients with systemic sclerosis.

PURPOSE: Outcomes after total knee arthroplasty (TKA) for patients with systemic sclerosis (SSc) are poorly documented in the literature. The purpose of this study was to evaluate SSc as a potential risk factor for increased rate of complications after TKA. METHODS: Using the PearlDiver Mariner database, 2,002 patients with SSc undergoing primary TKA were identified and compared to matched controls of 19,892 patients without SSc. Multivariable logistic regression analyses were done for medical complications up to 90 days and surgical complications up to two years. 90-day ED-visit and inpatient readmission were also documented. RESULTS: Compared to the matched controls, patients with SSc demonstrated higher rates of medical complications such as cerebrovascular accident (1.5% vs 0.6%, p < 0.001), myocardial infarction (1.3% vs 0.3%, p < 0.001), and sepsis (1.1% vs 0.4%, p < 0.001). Additionally, patients with SSc displayed elevated rates of surgical complications, including wound complications (3.9% vs 2.2%, p < 0.001) and aseptic loosening at 90 days (0.2% vs 0.1%; OR 3.53 [1.13-9.28]), one year (0.7% vs 0.4%; OR 1.78 [0.96-3.05]), and two years (1.4% vs 0.9%; OR 1.68 [1.10-2.45]). Patients with SSc also had higher rates of emergency department visits (21.2% vs 11.4%, p < 0.001). CONCLUSIONS: Patients with SSc are at higher risks of postoperative complications, encompassing both medical and surgical complications. Specifically, patients with SSc have a significantly higher likelihood of experiencing wound complications, cerebrovascular accident, and myocardial infarction. It is crucial for orthopaedic surgeons and patients alike to consider the elevated risks when determining a course of TKA for patients with SSc.

The impact of Behcet syndrome on total knee arthroplasty outcomes: a retrospective matched cohort study.

PURPOSE: Articu lar involvement is a common manifestation of Behcet syndrome (BS), which can eventually result in significant arthralgia and necessitate total knee arthroplasty (TKA). However, outcomes of BS patients after TKA are still poorly documented in the literature. The purpose of this study was to evaluate BS as a potential risk factor for complications after TKA. METHODS: BS patients undergoing primary TKA were identified from the PearlDiver Mariner database from 2010 to 2021 and compared to 10:1 matched controls. Multivariable logistic regression analyses were done for medical complications up to 90 days and surgical complications up to two years. Ninety-day emergency department (ED) visit and inpatient readmission were also documented. RESULTS: A total of 4286 patients undergoing primary TKA were queried, of which 390 had BS. Patients with BS demonstrated significantly higher rates of medical complications, including deep venous thrombosis. The rates of surgical complications were similar between the two groups with the exception of periprosthetic instability, aseptic loosening, and wound complications in BS patients. Additionally, a significantly higher rate of ED visits but markedly lower rates of 90-day readmissions were noted in patients with BS. CONCLUSION: Patients with BS undergoing TKA are at higher risks of medical and surgical complications. Special considerations for a unique postoperative course with the higher complications should be made. It is crucial for orthopedic surgeons and patients alike to consider these risks when determining the expected course after TKA for patients with BS.

The 2021 Association Research Circulation Osseous Classification for Early-Stage Osteonecrosis of the Femoral Head to Computed Tomography-Based Study.

BACKGROUND: The Association Research Circulation Osseous developed a novel classification for early-stage (precollapse) osteonecrosis of the femoral head (ONFH). We hypothesized that the novel classification is more reliable and valid when compared to previous 3 classifications: Steinberg, modified Kerboul, and Japanese Investigation Committee classifications. METHODS: In the novel classification, necrotic lesions were classified into 3 types: type 1 is a small lesion, where the lateral necrotic margin is medial to the femoral head apex; type 2 is a medium-sized lesion, with the lateral necrotic margin being between the femoral head apex and the lateral acetabular edge; and type 3 is a large lesion, which extends outside the lateral acetabular edge. In a derivation cohort of 40 early-stage osteonecrotic hips based on computed tomography imaging, reliabilities were evaluated using kappa coefficients, and validities to predict future femoral head collapse by chi-squared tests and receiver operating characteristic curve analyses. The predictability for future collapse was also evaluated in a validation cohort of 104 early-stage ONFH. RESULTS: In the derivation cohort, interobserver reliability (k = 0.545) and intraobserver agreement (63%-100%) of the novel method were higher than the other 3 classifications. The novel classification system was best able to predict future collapse (P < .05) and had the best discrimination between non-progressors and progressors in both the derivation cohort (area under the curve = 0.692 [0.522-0.863], P < .05) and the validation cohort (area under the curve = 0.742 [0.644-0.841], P = 2.46 × 10-5). CONCLUSION: This novel classification is a highly reliable and valid method of those examined. Association Research Circulation Osseous recommends using this method as a unified classification for early-stage ONFH. LEVEL OF EVIDENCE: Level III, diagnostic study.

Association of Fpr1 gene expression with osteogenesis and adipogenesis of adipose derived stem cells.

Formyl peptide receptors (Fprs) play fundamental roles in multiple cell functions including promotion of osteogenesis and bone fracture healing. In this study, the role of Fpr1 gene in osteogenic and adipogenic differentiation of adipose derived stem cells (ADSCs) was investigated. Primary ADSCs (mADSCs) from either Fpr1 knockout (KO) or wild type (WT) mice and human ADSCs (hADSCs) were treated by osteogenic (OM) or adipogenic (AM) medium, with basal medium as control. Osteogenesis and adipogenesis were measured by histological and biochemical methods. In both hADSCs and mADSCs, Fpr1 gene expression, osteogenic gene expression, as well as mineralization were increased after osteogenic induction. The osteogenic capacity of KO ADSCs was remarkably reduced compared to WT ADSCs, with decreased levels of expression of osteogenic markers, alkaline phosphatase activity, and mineralization. In contrast, the adipogenesis of KO ADSCs was remarkably enhanced compared with WT ADSCs, forming more lipid droplets, and increasing expression of adipogenic markers PPARγ and aP2. Expression of the nuclear transcription factor Forkhead box protein O1 (FoxO1) was decreased in KO ADSCs, while OM and AM caused increase and decrease in FoxO1 expression, respectively. The current study revealed a correlation of Fpr1 gene expression with osteogenesis and adipogenesis of mADSCs, underlying a mechanism involving FoxO1. Our present research suggests that targeting Fpr1 might be a novel strategy to enhance osteogenesis of ADSCs.

ARCO Consensus on the Pathogenesis of Non-traumatic Osteonecrosis of the Femoral Head.

Osteonecrosis of the femoral head (ONFH) is a devastating disease frequently leading to femoral head collapse and hip arthritis. Specifically, non-traumatic ONFH primarily affects young and middle-aged adults. Although compromised local circulation of the femoral head seems to be pathognomonic for the disease, the pathogenesis is perplexing and continues to be an area of scrutiny and research. Comprehension of the pathogenesis is of crucial importance for developing and guiding treatments for the disease. Therefore, we provide an up-to-date consensus on the pathogenesis of non-traumatic ONFH.

Osteonecrosis of the Femoral Head: an Updated Review of ARCO on Pathogenesis, Staging and Treatment.

Non-traumatic osteonecrosis of the femoral head (ONFH) usually affects adults younger than 50 years and frequently leads to femoral head collapse and subsequent arthritis of the hip. It is becoming more prevalent along with increasing use of corticosteroids for the adjuvant therapy of leukemia and other myelogenous diseases as well as management of organ transplantation. This review updated knowledge on the pathogenesis, classification criteria, staging system, and treatment of ONFH.

Diagnosis and Treatment of Femoral Head Osteonecrosis: A Protocol for Development of Evidence-Based Clinical Practice Guidelines.

INTRODUCTION: There are many treatment options for patients who have osteonecrosis of the femoral head (ONFH) and management strategies vary widely both among and within individual countries. Although many researchers have attempted to elucidate the optimal strategies for managing this disease, the lack of large-scale randomized control trials and the lack of agreement on disease staging have curtailed the development of clear-cut guidelines. MATERIALS AND METHODS: The Association Research Circulation Osseous (ARCO) group sought to address three questions for the management of patients who have ONFH: 1) What imaging studies are most sensitive and specific for the diagnostic evaluation of patients who have ONFH?; 2) What is the best treatment strategy for preventing disease progression in patients who have pre-collapse lesions?; and 3) What is the best treatment strategy for patients who have post-collapse disease? The Patient, Intervention, Comparison, and Outcome (PICO) format was used to formulate the search strategy for each research question. A systematic review will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. ARCO participants have been allocated to three groups, each representing one of the PICO questions. After qualitative and quantitative analysis of the data extracted from studies pertaining to each of the three research questions, a set of evidence-based clinical practice guidelines will be proposed for the management of patients who have ONFH. DISCUSSION: It is not always clear which treatment method is optimal for the management of ONFH. Thus, many surgeons have developed and performed various procedures based on patient-specific factors. As there is no consensus on the optimal treatment for various stages of disease, it was clear that developing evidence-based clinical practice guidelines would provide more structure and uniformity to management of these patients. Therefore, the results of this systematic review will lead to the development guidelines that may improve patient-care strategies and result in better outcomes for patients who have ONFH.

Bromosulfophthalein suppresses inflammatory effects in lipopolysaccharide-stimulated RAW264.7 macrophages.

OBJECTIVE: It has been reported that glutathione (GSH), the most abundant cellular antioxidant, can inhibit production of pro-inflammatory cytokines by activated macrophages. Bromosulfophthalein (BSP) has been recognized as an inhibitor of the efflux of reduced GSH from cells, leading to an increase in the intracellular GSH level. In this study, we evaluated, for the first time, whether BSP possessed anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated macrophages. MATERIALS AND METHODS: RAW 264.7 cells were treated with BSP and the levels of proinflammatory cytokines, GSH, and nitrite were assessed. Gene expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF α), interleukin-1beta (IL-1ß), and interleukin-6 (IL-6) was analyzed via quantitative RT-PCR. We also examined various inflammatory signaling pathways including Akt/forkhead box protein O1 (FoxO1)/toll-like receptor 4 (TLR4), mitogen-activated protein kinases (MAPKs), and Fas protein by Western blot and flow cytometry analysis. RESULTS: Our study demonstrated that BSP induced an increase in intracellular GSH level in LPS-stimulated macrophages. BSP inhibited production of nitric oxide and proinflammatory cytokines. BSP increased phosphorylation of Akt and nuclear exclusion of FoxO1 and suppressed TLR4 expression. Additionally, BSP decreased MAPKs activation and Fas expression. DISCUSSION AND CONCLUSION: Taken together, these data suggest that BSP can attenuate inflammation through multiple signaling pathways. These findings highlight the potential of BSP as a new anti-inflammatory agent.

Outcomes Following Revision Joint Arthroplasty Among Hemodialysis-Dependent Patients.

BACKGROUND: Hemodialysis (HD) dependence is known to impact the integrity of bone and has long been associated with metabolic bone disease and other adverse events postoperatively. The aim of this study is to analyze postoperative outcomes following revision hip and knee arthroplasty in hemodialysis-dependent (HDD) patients and to characterize the common indications for revision procedures among this patient population. METHODS: A total of 1779 HDD patients who underwent a revision joint arthroplasty (930 revision total knee arthroplasty [TKA] and 849 revision total hip arthroplasty [THA]) between 2005 and 2014 were identified from a retrospective database review. Our resulting study groups of revision TKA and THA HDD patients were compared to their respective matched control groups for hospital length of stay (LOS), 90-day mean total cost, hospital readmission, and other major medical and surgical complications. RESULTS: HD was significantly associated with increased LOS (7.7 ± 8.3 vs 4.8 ± 4.5; P < .001), mean 90-day total cost ($47,478 ± $33,413 vs $24,286 ± $21,472; P < .001), hospital readmission (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.96-2.58; P < .001), septicemia (OR, 3.18; 95% CI, 2.70-3.74; P < .001), postoperative infection (OR, 1.72; 95% CI, 1.50-1.98; P < .001), and mortality (OR, 3.99; 95% CI, 3.12-5.06; P < .001) following revision TKA. Among revision THA patients, HD was associated with increased LOS (9.4 ± 9.5 vs 5.7 ± 5.7; P < .001), mean 90-day total cost ($40,182 ± $27,082 vs $26,519 ± $22,856; P < .001), hospital readmission (OR, 2.33; 95% CI, 2.02-2.68; P < .001), septicemia (OR, 3.61; 95% CI, 3.05-4.27; P < .001), and mortality (OR, 3.55; 95% CI, 2.86-4.37; P < .001). CONCLUSION: HD remains a significant risk factor for increased LOS, mean total cost, hospital readmission, septicemia, and mortality following revision joint arthroplasty.

The 2019 Revised Version of Association Research Circulation Osseous Staging System of Osteonecrosis of the Femoral Head.

BACKGROUND: The Association Research Circulation Osseous (ARCO) presents the 2019 revised staging system of osteonecrosis of the femoral head (ONFH) based on the 1994 ARCO classification. METHODS: In October 2018, ARCO established a task force to revise the staging system of ONFH. The task force involved 29 experts who used a web-based survey for international collaboration. Content validity ratios for each answer were calculated to identify the levels of agreement. For the rating queries, a consensus was defined when more than 70% of the panel members scored a 4 or 5 rating on a 5-point scale. RESULTS: Response rates were 93.1%-100%, and through the 4-round Delphi study, the 1994 ARCO classification for ONFH was successfully revised. The final consensus resulted in the following 4-staged system: stage I-X-ray is normal, but either magnetic resonance imaging or bone scan is positive; stage II-X-ray is abnormal (subtle signs of osteosclerosis, focal osteoporosis, or cystic change in the femoral head) but without any evidence of subchondral fracture, fracture in the necrotic portion, or flattening of the femoral head; stage III-fracture in the subchondral or necrotic zone as seen on X-ray or computed tomography scans. This stage is further divided into stage IIIA (early, femoral head depression ≤2 mm) and stage IIIB (late, femoral head depression >2 mm); and stage IV-X-ray evidence of osteoarthritis with accompanying joint space narrowing, acetabular changes, and/or joint destruction. This revised staging system does not incorporate the previous subclassification or quantitation parameters, but the panels agreed on the future development of a separate grading system for predicting disease progression. CONCLUSION: A staging system has been developed to revise the 1994 ARCO classification for ONFH by an expert panel-based Delphi survey. ARCO approved and recommends this revised system as a universal staging of ONFH.

Etiologic Classification Criteria of ARCO on Femoral Head Osteonecrosis Part 1: Glucocorticoid-Associated Osteonecrosis.

BACKGROUND: Glucocorticoid usage, a leading cause of osteonecrosis of the femoral head (ONFH), and its prevalence was reported in 25%-50% of non-traumatic ONFH patients. Nevertheless, there have been no unified criteria to classify glucocorticoid-associated ONFH (GA-ONFH). In 2015, the Association Research Circulation Osseous addressed the issue of developing a classification scheme. METHODS: In June 2017, a task force was set up to conduct a Delphi survey concerning ONFH. The task force invited 28 experts in osteonecrosis/bone circulation from 8 countries. Each round of the Delphi survey consists of questionnaires, analysis of replies, and feedback reports to the panel. After 3 rounds of the survey, the panel reached a consensus on the classification criteria. The response rates were 100% (Round 1), 96% (Round 2), and 100% (Round 3), respectively. RESULTS: The consensus on the classification criteria of GA-ONFH included the following: (1) patients should have a history of glucocorticoid use >2 g of prednisolone or its equivalent within a 3-month period; (2) osteonecrosis should be diagnosed within 2 years after glucocorticoid usage, and (3) patients should not have other risk factor(s) besides glucocorticoids. CONCLUSION: Association Research Circulation Osseous established classification criteria to standardize clinical studies concerning GA-ONFH.