Increased mortality after total hip prosthetic joint infection is mainly caused by the comorbidities rather than the infection itself.

BACKGROUND AND PURPOSE: Periprosthetic joint infection (PJI) is a feared complication of arthroplasty surgery. There is controversy as to whether PJI also correlates with increased mortality. Our aim was to investigate in a nationwide cohort if PJI is an independent risk factor for dying. PATIENTS AND METHODS: We performed a retrospective cohort study based on data from the Swedish Hip Arthroplasty Register (SHAR). All patients with a revision THA performed between 1998 and 2017 were included. The outcome is mortality; exposure is PJI according to SHAR. The control group was study participants who underwent aseptic revision. Confounders were age, sex, diagnosis, and comorbidity according to the Elixhauser index. The outcome was analyzed with a Cox proportional hazards model. RESULTS: 4,943 PJI revisions and 12,529 non-infected revisions were included in the analysis. The median follow-up time was 4.1 years. In the PJI group, 1,972 patients died and in the control group, 4,512. The incidence rate ratio was 1.19 (95% confidence interval [CI] 1.13-1.25), the crude hazard ratio (HR) 1.19 (CI 1.13-1.25), and the adjusted HR 1.05 (CI 0.99-1.12) for the exposed versus the unexposed group. The strongest confounder was comorbidity. CONCLUSION: The increased mortality risk after revision due to PJI is mainly caused by the comorbidity of the patient, rather than by the infection itself.

Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines.

The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. Inflammatory markers in plasma and SF in OA patients and controls were measured using a 44-multiplex immunoassay. We found consistently 29 markers detected in both plasma and SF. The difference in their concentration and the low correlation when comparing SF and plasma suggests an independent inflammatory environment in the two biofluids. Only plasma MCP-4 and TARC increased in our patient cohort compared to control plasma. To address the second task, we concluded that plasma markers were irrelevant for a direct connection with SF glycosylation. Hence, we correlated the SF-inflammatory marker concentrations with the level of altered glycosylation of SF-lubricin. We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. These data suggest that truncated glycans of lubricin, as found in OA, promote synovial proinflammatory cytokine production and exacerbate local synovial inflammation.

EPOS trial: the effect of air filtration through a plasma chamber on the incidence of surgical site infection in orthopaedic surgery: a study protocol of a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: There is controversy regarding the importance of air-transmitted infections for surgical site infections (SSIs) after orthopaedic surgery. Research has been hindered by both the inability in blinding the exposure, and by the need for recruiting large enough cohorts. The aim of this study is to investigate whether using a new form of air purifier using plasma air purification (PAP) in operating rooms (ORs) lowers the SSI rate or not. METHODS AND ANALYSIS: Multicentre, double-blind, cluster-randomised, placebo-controlled trial conducted at seven hospitals in 2017-2022. All patients that undergo orthopaedic surgery for minimum 30 min are included. Intervention group: patients operated in OR with PAP devices turned on. CONTROL GROUP: patients operated in OR with PAP devices turned off. Randomisation: each OR will be randomised in periods of 4 weeks, 6 weeks or 8 weeks to either have the devices on or off. PRIMARY OUTCOME: any SSI postoperatively defined as a composite endpoint of any of the following: use of isoxazolylpenicillin, clindamycin or rifampicin for 2 days or more, International Classification of Diseases codes or Nordic Medico-Statistical Committee codes indicating postoperative infection. In a second step, we will perform a chart review on those patients with positive indicators of SSI to further validate the outcome. Secondary outcomes are described in the Methods section. Power: we assume an SSI rate of 2%, an SSI reduction rate of 25% and we need approximately 45 000 patients to attain a power of 80% at a significance level of 0.05. ETHICS AND DISSEMINATION: The study is approved by the Swedish Ethical Review Authority. The interim analysis results from the study will be presented only to the researchers involved unless the study thereafter is interrupted for whatever reason. Publication in a medical journal will be presented after inclusion of the last patient. TRIAL REGISTRATION NUMBER: NCT02695368.

The Sernbo score as a predictor of 1-year mortality after hip fracture: a registry study on 55,716 patients.

PURPOSE: Patients sustaining a hip fracture have a high mortality rate during the first postoperative year and the Sernbo score may stratify patients into a high, intermediate and low risk of death during this period. We assessed its predictive properties on patients from the National Swedish Hip Fracture Register. PATIENTS AND METHODS: 55,716 hip fracture patients, 69% women older than 65 years at surgery (registered between 2010 and 2015) with complete Sernbo scores and mortality data were studied. Receiver-operating characteristics analyses (ROC) were used. Validation of Sernbo score was performed. RESULTS: The overall 1-year mortality rate was 26%-and 17%, 27.4% and 55.6% in the low, intermediate and high-risk groups, respectively. The ROC analysis indicated a predictive ability of the Sernbo score, with an AUC of 0.69 (CI 0.68-0.69). CONCLUSION: In this registry-based study, the easy-to-use Sernbo scoring system proved to be appropriate and useful way to identify hip fracture patients with a high-risk mortality during the first postoperative year.

Decrease of core 2 O-glycans on synovial lubricin in osteoarthritis reduces galectin-3 mediated crosslinking.

The synovial fluid glycoprotein lubricin (also known as proteoglycan 4) is a mucin-type O-linked glycosylated biological lubricant implicated to be involved in osteoarthritis (OA) development. Lubricin's ability to reduce friction is related to its glycosylation consisting of sialylated and unsialylated Tn-antigens and core 1 and core 2 structures. The glycans on lubricin have also been suggested to be involved in crosslinking and stabilization of the lubricating superficial layer of cartilage by mediating interaction between lubricin and galectin-3. However, with the spectrum of glycans being found on lubricin, the glycan candidates involved in this interaction were unknown. Here, we confirm that the core 2 O-linked glycans mediate this lubricin-galectin-3 interaction, shown by surface plasmon resonance data indicating that recombinant lubricin (rhPRG4) devoid of core 2 structures did not bind to recombinant galectin-3. Conversely, transfection of Chinese hamster ovary cells with the core 2 GlcNAc transferase acting on a mucin-type O-glycoprotein displayed increased galectin-3 binding. Both the level of galectin-3 and the galectin-3 interactions with synovial lubricin were found to be decreased in late-stage OA patients, coinciding with an increase in unsialylated core 1 O-glycans (T-antigens) and Tn-antigens. These data suggest a defect in crosslinking of surface-active molecules in OA and provide novel insights into OA molecular pathology.

A cohort study comparing internal fixation for undisplaced versus hip arthroplasty for displaced femoral neck fracture in the elderly: a pilot study for a clinical trial.

INTRODUCTION: The literature regarding undisplaced femoral neck fractures (FNF) is sparse. The aim of this prospective feasibility study is to compare the clinical outcome after undisplaced FNF treated with internal fixation (IF) and displaced FNF treated with hip arthroplasty. We hypothesized that hip arthroplasty would give a lower incidence of reoperations. METHODS: A total of 235 patients were included with a median age of 84 years (range 65-99). A consecutive series of 65 patients with undisplaced FNF were treated with IF, and 170 patients with displaced FNF were treated with either a total hip arthroplasty or a hemiarthroplasty. Follow-up interviews were conducted at 1 year using the Harris Hip Score (HHS), WOMAC, and pain numeric rating scale (PNRS). The minimum follow-up time was 22 months. There was no difference in baseline data between the groups. RESULTS: Nineteen (8%) hips required reoperation at least once at a mean of 6 months (range 0-35). The rate of reoperation was higher in the IF group compared to the hip arthroplasty group (13.8% vs. 5.9%, 95% CI 0.9-6.4). The overall 1-year and 2-year mortality was 28% and 40%, respectively, with no difference between the groups. The most common reasons for reoperations in the IF group were non-union and avascular necrosis, and 6 patients were treated with hip or excision arthroplasty. In the arthroplasty group, the most common indications were deep infection and dislocation. We did not find any differences between the groups in terms of HHS, WOMAC, and PNRS. CONCLUSIONS: In this feasibility study, we found no differences in patient-reported outcomes between the groups although IF required a higher rate of reoperations. Further randomized trials are needed to establish the optimal treatment of undisplaced FNF in the elderly. TRIAL REGISTRATION: ClinicalTrial.org, NCT03392285. Retrospectively registered on 5 February 2018.

Cathepsin g Degrades Both Glycosylated and Unglycosylated Regions of Lubricin, a Synovial Mucin.

Lubricin (PRG4) is a mucin type protein that plays an important role in maintaining normal joint function by providing lubrication and chondroprotection. Improper lubricin modification and degradation has been observed in idiopathic osteoarthritis (OA), while the detailed mechanism still remains unknown. We hypothesized that the protease cathepsin G (CG) may participate in degrading lubricin in synovial fluid (SF). The presence of endogenous CG in SF was confirmed in 16 patients with knee OA. Recombinant human lubricin (rhPRG4) and native lubricin purified from the SF of patients were incubated with exogenous CG and lubricin degradation was monitored using western blot, staining by Coomassie or Periodic Acid-Schiff base in gels, and with proteomics. Full length lubricin (∼300 kDa), was efficiently digested with CG generating a 25-kDa protein fragment, originating from the densely glycosylated mucin domain (∼250 kDa). The 25-kDa fragment was present in the SF from OA patients, and the amount was increased after incubation with CG. A CG digest of rhPRG4 revealed 135 peptides and 72 glycopeptides, and confirmed that the protease could cleave in all domains of lubricin, including the mucin domain. Our results suggest that synovial CG may take part in the degradation of lubricin, which could affect the pathological decrease of the lubrication in degenerative joint disease.

A randomized double-blind noninferiority trial, evaluating migration of a cemented vitamin E-stabilized highly crosslinked component compared with a standard polyethylene component in reverse hybrid total hip arthroplasty.

AIMS: Radiostereometric analysis (RSA) studies of vitamin E-doped, highly crosslinked polyethylene (VEPE) liners show low head penetration rates in cementless acetabular components. There is, however, currently no data on cemented VEPE acetabular components in total hip arthroplasty (THA). The aim of this study was to evaluate the safety of a new cemented VEPE component, compared with a conventional polyethylene (PE) component regarding migration, head penetration, and clinical results. PATIENTS AND METHODS: We enrolled 42 patients (21 male, 21 female) with osteoarthritis and a mean age of 67 years (sd 5), in a double-blinded, noninferiority, randomized controlled trial. The subjects were randomized in a 1:1 ratio to receive a reverse hybrid THA with a cemented component of either argon-gas gamma-sterilized PE component (controls) or VEPE, with identical geometry. The primary endpoint was proximal implant migration of the component at two years postoperatively measured with RSA. Secondary endpoints included total migration of the component, penetration of the femoral head into the component, and patient-reported outcome measurements. RESULTS: In total, 19 control implants and 18 implants in the VEPE group were analyzed for the primary endpoint. We found a continuous proximal migration of the component in the VEPE group that was significantly higher with a difference at two years of a mean 0.21 mm (95% confidence interval (CI) 0.05 to 0.37; p = 0.013). The total migration was also significantly higher in the VEPE group, but femoral head penetration was lower. We found no difference in clinical outcomes between the groups. CONCLUSION: At two years, this cemented VEPE component, although having a low head penetration and excellent clinical results, failed to meet noninferiority compared with the conventional implant by a proximal migration above the proposed safety threshold of RSA. The early proximal migration pattern of the VEPE component is a reason for continued monitoring, although a specific threshold for proximal migration and risk for later failure cannot be defined and needs further study. Cite this article: Bone Joint J 2019;101-B:1192-1198.

Aseptic loosening after total hip arthroplasty and the risk of cardiovascular disease: A nested case-control study.

BACKGROUND: Patients with surgically treated osteoarthritis of the hip have an increased risk of cardiovascular morbidity and mortality many years after the operation compared with controls. Our hypothesis is that this increased risk after total hip arthroplasty (THA) is mediated by development of periprosthetic osteolysis leading to aseptic loosening of the implant. METHODS: We conducted a nation-wide, nested, case-control study consisting of patients receiving a cemented THA due to osteoarthritis between the years 1992 and 2005. Our study population included a total of 14,430 subjects identified in the Swedish hip arthroplasty register and linked to the Swedish National Patient Register. The case group consisted of patients (n = 2,886) who underwent reoperation of the treated hip due to osteolysis or aseptic loosening at any time within five years after the index surgery. Each case was matched with four controls (n = 11,544) who had not undergone reoperation. The main outcomes were cardiovascular events i.e. myocardial infarction, heart failure and cerebral infarction according to ICD-codes and time to the first cardiovascular event during the exposure period. Outcomes were subgrouped into cardiac and cerebral events. We used regression models to calculate the incidence rates and adjusted our results for confounders. FINDINGS: Overall, 5.1% of patients had cardiac events, with slightly more overall cardiovascular events occurring in the control group (8.1% vs. 6.7%, odds ratio 0.8, 95% confidence interval (CI) 0.7 to 1.0). After adjusting for confounders, the case group had an increased relative risk of 1.3 (95% confidence interval (CI) 1.1 to 1.3) for total number of cardiovascular events. Similar effect sizes were observed for time to first event. INTERPRETATION: Patients with osteoarthritis who received THA and subsequently underwent a revision operation due to loosening had a higher relative risk of developing cardiovascular events than controls. Thus there is an association which could be explained by a common inflammatory disease pathway that requires further experimental research.

Revision for Symptomatic Pseudotumor After Primary Metal-on-Polyethylene Total Hip Arthroplasty with a Standard Femoral Stem.

BACKGROUND: Pseudotumor formation following total hip arthroplasty (THA) is a well-known complication mainly associated with metal-on-metal (MoM) bearings and taper corrosion on modular-neck femoral stems. The purpose of this study was to determine the prevalence of revision surgery for symptomatic pseudotumors in a large cohort of patients treated with primary THA with a standard stem and a non-MoM articulation. METHODS: We included 2,102 patients treated with a total of 2,446 THAs from 1999 until May 2016 in a prospective, observational cohort study. All patients underwent THA with the same uncemented, non-modular-neck femoral stem and metal-on-polyethylene (MoP) (n = 2,409) or ceramic-on-polyethylene (n = 37) articulation. All patients were followed by means of a combination of surgical and medical chart review, follow-up visits, and the Swedish Hip Arthroplasty Register. Metal artifact reduction sequence magnetic resonance imaging (MARS MRI) was used for diagnosis of the pseudotumors, and serum metal ion levels and inflammatory marker levels were measured for all patients who underwent a revision due to pseudotumor. RESULTS: The prevalence of revision for symptomatic pseudotumor formation was 0.5% (13 cases) at a mean follow-up time of 7 years. The incidence rate was 0.9 case per 1,000 person-years. All 13 revisions were done in patients with an MoP articulation. CONCLUSIONS: This study demonstrated a 0.5% prevalence of revision due to symptomatic pseudotumor formation in a cohort of patients who underwent THA with a non-MoM construct. Surgeons should be aware that symptomatic pseudotumor formation requiring revision surgery is a tangible complication even after standard MoP THA. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Nurses' Experience of Patient Care in Multibed Hospital Rooms: Results From In-Depth Interviews With Nurses After Further Education in Anesthesia.

PURPOSE: The purpose of this study was to investigate and explore nurse's previous experiences of patient care in MBRs before their further education in anesthesia. DESIGN: Qualitative research. METHODS: Data were collected through three focus group interviews using content data analysis. FINDINGS: Maintaining patient privacy, providing conditions for communication between health care professionals and patients, and undertaking daily practical care were stated as the main problems in MBR care. Inferior conditions for providing sensitive information and communication with proxies, especially in association with language problems, were frequently encountered. Patient's proxies could facilitate several problematic issues in MBR care. CONCLUSIONS: The present study characterized well-defined and easily recognizable clinical problems experienced in the care of patients in an MBR setting from a nurse's perspective. The opinion shared by most nurses was that the inability to implement privacy, dignity, and sound communication with patients should be taken into account in future hospital designs. General dissatisfaction with work environment, increased stress, and the risk of errors in care may otherwise follow.

Lubricin binds cartilage proteins, cartilage oligomeric matrix protein, fibronectin and collagen II at the cartilage surface.

Lubricin, a heavily O-glycosylated protein, is essential for boundary lubrication of articular cartilage. Strong surface adherence of lubricin is required given the extreme force it must withstand. Disulfide bound complexes of lubricin and cartilage oligomeric matrix protein (COMP) have recently been identified in arthritic synovial fluid suggesting they may be lost from the cartilage surface in osteoarthritis and inflammatory arthritis. This investigation was undertaken to localise COMP-lubricin complexes within cartilage and investigate if other cartilage proteins are involved in anchoring lubricin to the joint. Immunohistochemical analysis of human cartilage biopsies showed lubricin and COMP co-localise to the cartilage surface. COMP knockout mice, however, presented with a lubricin layer on the articular cartilage leading to the further investigation of additional lubricin binding mechanisms. Proximity ligation assays (PLA) on human cartilage biopsies was used to localise additional lubricin binding partners and demonstrated that lubricin bound COMP, but also fibronectin and collagen II on the cartilage surface. Fibronectin and collagen II binding to lubricin was confirmed and characterised by solid phase binding assays with recombinant lubricin fragments. Overall, COMP, fibronectin and collagen II bind lubricin, exposed on the articular cartilage surface suggesting they may be involved in maintaining essential boundary lubrication.

Osteoclasts in Periprosthetic Osteolysis: The Charnley Arthroplasty Revisited.

BACKGROUND: Periprosthetic osteolysis by polyethylene wear debris-triggered osteoclasts is viewed as the main pathophysiological pathway in aseptic loosening in total hip arthroplasty. The present aim was to study osteoclast occurrence in osteolytic lesions in early and late revisions of the Charnley low-friction torque arthroplasty (CLFA). METHODS: Biopsies of the soft interface membrane and the adjacent bone were taken from osteolytic lesions during revision of 16 loose CLFA, early (2-6 years) or late (>10 years) after primary surgery. By light microscopy (LM), cell-dense regions with signs of osteoclast-mediated bone resorption were selected for transmission electron microscopy. Three additional patients were studied in LM for osteoclast markers (tartrate-resistant acid phosphatase and Cathepsin K). RESULTS: LM disclosed a low-grade chronic inflammation and birefringent particles in most sections. Multiple conglomerates of tartrate-resistant acid phosphatase positive and Cathepsin K positive mononuclear and multinucleated cells were found deep in the fibrous interface membrane. Transmission electron microscopy showed traces of polyethylene-like particles in 67%-100% of the cells. Osteoclast-like cells exhibiting resorptive activity were few (mean, 0.7%; standard deviation, 0.2%), and multinucleated cells, possibly osteoclast precursor cells, located immediately on the bone were also scarce (mean, 2.7%; standard deviation, 5.3%). Multinucleated (odds ratio, 3.0; 95% confidence interval, 1.7-5.5) and macrophage-like cells (odds ratio, 3.6; 95% confidence interval, 2.2-5.6) were typically located deeper in the inflammatory interface membrane with a pathologic appearance with distension and abundance of phagocytic vacuoles. There were no systematic differences in cell populations between early or late revisions. CONCLUSION: Despite probable ongoing osteoclastogenesis in the osteolytic lesions, there were few sites of osteoclast-mediated bone resorption. These findings attach a contributing biological explanation to the longevity of the CLFA.

The Sernbo score predicts 1-year mortality after displaced femoral neck fractures treated with a hip arthroplasty.

Background and purpose - Displaced femoral neck fractures (FNFs) are associated with high rates of mortality during the first postoperative year. The Sernbo score (based on age, habitat, mobility, and mental state) can be used to stratify patients into groups with different 1-year mortality. We assessed this predictive ability in patients with a displaced FNF treated with a hemiarthroplasty or a total hip arthroplasty. Patients and methods - 292 patients (median age 83 (65-99) years, 68% female) with a displaced FNF were included in this prospective cohort study. To predict 1-year mortality, we used a multivariate logistic regression analysis including comorbidities and perioperative management. A receiver operating characteristic (ROC) analysis was used to evaluate the predictive ability of the Sernbo score, which was subsequently divided in a new manner into a low, intermediate, or high risk of death during the first year. Results - At 1-year follow-up, the overall mortality rate was 24%, and in Sernbo's low-, intermediate-, and high-risk groups it was 5%, 22%, and 51%, respectively. The Sernbo score was the only statistically significant predictor of 1-year mortality: odds ratio for the intermediate-risk group was 4.2 (95% Cl: 1.5-12) and for the high-risk group it was 15 (95% CI: 5-40). The ROC analysis showed a fair predictive ability of the Sernbo score, with an area under the curve (AUC) of 0.79 (95% CI: 0.73-0.83). Using a cutoff of less than 11 points on the score gave a sensitivity of 61% and a specificity of 83%. Interpretation - The Sernbo score identifies patients who are at high risk of dying in the first postoperative year. This scoring system could be used to better tailor perioperative care and treatment in patients with displaced FNF.

Early periprosthetic joint infection and debridement, antibiotics and implant retention in arthroplasty for femoral neck fracture.

INTRODUCTION: Periprosthetic joint infection (PJI) is a severe complication of hip arthroplasty for femoral neck fractures (FNF). Debridement, antibiotics and implant retention (DAIR) is recommended in early PJI in association with stable implants. Few studies have evaluated the outcome of DAIR in this fragile population.The purpose of this study was to analyse risk factors for PJI and the short-term outcome of DAIR in FNF patients treated with a hip arthroplasty. METHODS: A consecutive series of 736 patients (median age 81 years, 490 women, 246 men) had been treated with either a total hip arthroplasty or a hemi hip arthroplasty for a displaced FNF at our institution. 33 (4.5%) of the hips developed an early (<6 weeks post operatively) PJI and 28 (3.8%) of these patients were treated according to the DAIR-protocol. Regression analyses were performed to assess risk factors for developing a PJI. RESULTS: DAIR eradicated the PJI in 82% (23/28) of patients at a median follow-up of 31 (SD 29.8) months of the infected hips.The logistic regression analysis indicated that 2 or more changes of the primary dressing due to wound bleeding was associated with an increased risk for developing PJI (OR 4.9, 95% 1.5 to 16.1, p = 0.01). CONCLUSIONS: The short-term success-rate of DAIR was unexpectedly favourable in this fragile patient population; the results being on par with that after PJI in osteoarthritis patients. The need for repeated bandage changes postoperatively indicates an increased risk for PJI and should prompt early surgical intervention.

Migration and head penetration of Vitamin-E diffused cemented polyethylene cup compared to standard cemented cup in total hip arthroplasty: study protocol for a randomised, double-blind, controlled trial (E1 HIP).

INTRODUCTION: In vitro, Vitamin-E-diffused, highly cross-linked polyethylene (PE) has been shown to have superior wear resistance and improved mechanical properties when compared to those of standard highly cross-linked PE liners used in total hip arthroplasty (THA). The aim of the study is to evaluate the safety of a new cemented acetabular cup with Vitamin-E-doped PE regarding migration, head penetration and clinical results. METHODS AND ANALYSIS: In this single-centre, double-blinded, randomised controlled trial, we will include 50 patients with primary hip osteoarthritis scheduled for THA and randomise them in a 1:1 ratio to a cemented cup with either argon gas-sterilised PE (control group) or Vitamin-E-diffused PE (vitamin-e group). All patients and the assessor of the primary outcome will be blinded and the same uncemented stem will be used for all participants. The primary end point will be proximal migration of the cup at 2 years after surgery measured with radiostereometry. Secondary end points include proximal migration at other follow-ups, total migration, femoral head penetration, clinical outcome scores and hip-related complications. Patients will be followed up at 3 months and at 1, 2, 5 and 10 years postoperatively. RESULTS: Results will be analysed using 95% CIs for the effect size. A regression model will also be used to adjust for stratification factors. ETHICS AND DISSEMINATION: The ethical committee at Karolinska Institutet has approved the study. The first results from the study will be disseminated to the medical community via presentations and publications in relevant medical journals when the last patient included has been followed up for 2 years. TRIAL REGISTRATION NUMBER: NCT02254980.

Denosumab for treating periprosthetic osteolysis; study protocol for a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Wear-induced osteolysis is the main factor in reducing the longevity of total hip arthroplasty (THA). The transmembrane Receptor Activator of Nuclear Factor κ B (RANK) and its corresponding ligand RANKL is an important regulator of osteoclast activity and bone resorption and is associated with osteolysis around implant. Inhibiting RANKL with denosumab is effective in vivo in preventing osteoporosis-related fractures. In vitro, osteoclasts can be blocked in animal models of osteolysis. We hypothesize that denosumab is effective in reducing wear-induced osteolysis around uncemented acetabular implants in THA. METHODS/DESIGN: A randomized, double-blind, placebo-controlled trial will be conducted. We will include 110 patients, 40-85 years of age, with a known osteolytic lesion around an uncemented acetabular component ≥7 years after the primary operation. The patients will be randomized in a 1:1 ratio to subcutaneous injections of 60 mg denosumab or placebo for a total of 6 doses with start on day one and every 6 months with last treatment at 30 months. The primary endpoint will be the change in volume of the osteolytic lesion at 3 years measured with three-dimensional computed tomography (3D-CT). Secondary endpoints include functional outcome scores, change in bone mineral density of the lumbar spine, serological markers of bone turnover and adverse events. DISCUSSION: In vitro results of both bisphosphonates and RANKL inhibitors have been promising, showing reduced osteolysis with treatment. This is, to our knowledge, the first clinical trial testing the efficacy of denosumab in reducing wear-induced osteolysis. The study is an academic, phase II trial from an independent center and is designed to demonstrate efficacy in reducing volume of osteolytic lesions around a total hip arthroplasty. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02299817) 2014-11-20.

Debridement, antibiotics and implant retention in early periprosthetic joint infection.

INTRODUCTION: Periprosthetic joint infection (PJI) is a devastating complication in hip arthroplasty surgery. Debridement, antibiotics (AB) and implant retention (DAIR) is recommended in early PJI in association with stable implants. The aim of this study was to evaluate the success rate of DAIR in early PJI (<4 weeks) and to identify factors predicting the outcome. METHODS: This cohort study included a consecutive series of 35 patients (median age 74 years, 25 women, 26 primary arthroplasties) treated with DAIR for an early PJI in a regional hospital. RESULTS: 28 patients (80%) had their infection eradicated. DAIR-only eradicated the PJI in 22 (63%) patients with a median follow-up of 50 (24-84) months. In 17 (49%) patients, oral AB had been given prior to intraoperative cultures, which delayed first debridement with average 6 days and delayed hospital stay. Primary surgery for a hip fracture increased the risk of DAIR-failure. Surgical experience did not affect the outcome. 17% (n = 6) of the patients sustained a secondary infection during their hospital stay; the majority was beta-lactam resistant coagulase negative Staphylococcus aureus. CONCLUSIONS: The success rate of DAIR was inferior to pervious controls from experienced revision centers. Hip fracture patients should be informed about the increased risk of DAIR treatment failure. In order not to delay surgery, empirically based oral AB should not be administered prior to deep cultures. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02087020.

Increased Long-Term Cardiovascular Risk After Total Hip Arthroplasty: A Nationwide Cohort Study.

Total hip arthroplasty is a common and important treatment for osteoarthritis patients. Long-term cardiovascular effects elicited by osteoarthritis or the implant itself remain unknown. The purpose of the present study was to determine if there is an increased risk of late cardiovascular mortality and morbidity after total hip arthroplasty surgery.A nationwide matched cohort study with data on 91,527 osteoarthritis patients operated on, obtained from the Swedish Hip Arthroplasty Register. A control cohort (n = 270,688) from the general Swedish population was matched 1:3 to each case by sex, age, and residence. Mean follow-up time was 10 years (range, 7-21).The exposure was presence of a hip replacement for more than 5 years. The primary outcome was cardiovascular mortality after 5 years. Secondary outcomes were total mortality and re-admissions due to cardiovascular events.During the first 5 to 9 years, the arthroplasty cohort had a lower cardiovascular mortality risk compared with the control cohort. However, the risk in the arthroplasty cohort increased over time and was higher than in controls after 8.8 years (95% confidence interval [CI] 7.0-10.5). Between 9 and 13 years postoperatively, the hazard ratio was 1.11 (95% CI 1.05-1.17). Arthroplasty patients were also more frequently admitted to hospital for cardiovascular reasons compared with controls, with a rate ratio of 1.08 (95% CI 1.06-1.11).Patients with surgically treated osteoarthritis of the hip have an increased risk of cardiovascular morbidity and mortality many years after the operation when compared with controls.