Aims. A revision for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) has a major effect on the patient’s quality of life, including walking capacity. The objective of this case control study was to investigate the histological and ultrastructural changes to the gluteus medius tendon (GMED) in patients revised due to a PJI, and to compare it with revision THAs without infection performed using the same lateral approach. Methods. A group of eight patients revised due to a PJI with a previous lateral approach was compared with a group of 21 revised THAs without infection, performed using the same approach. The primary variables of the study were the fibril diameter, as seen in transmission electron microscopy (TEM), and the total degeneration score (TDS), as seen under the light microscope. An analysis of bacteriology, classification of infection, and antibiotic treatment was also performed. Results. Biopsy samples from the GMED from infected patients revealed a larger fibril diameter than control patients, as seen in the TEM (p < 0.001). Uninfected patients were slightly older and had their revisions performed significantly later than the infected patients. Histologically, samples from infected patients revealed significantly more vascularity (p < 0.001), the presence of glycosaminoglycans (p < 0.001), and a higher TDS (p = 0.003) than the control patients. The majority of patients had staphylococcal infections of various species. Conclusion. More histological degeneration in the GMED was found in patients undergoing THA revision surgery due to PJI than in patients undergoing THA revision surgery due to other reasons. Cite this article: Bone Jt Open 2023;4(8):628–635

Aims. The duration of systemic antibiotic treatment following first-stage revision surgery for periprosthetic joint infection (PJI) after total hip arthroplasty (THA) is contentious. Our philosophy is to perform an aggressive debridement, and to use a high local concentration of targeted antibiotics in cement beads and systemic prophylactic antibiotics alone. The aim of this study was to assess the success of this philosophy in the management of PJI of the hip using our two-stage protocol. Methods. The study involved a retrospective review of our prospectively collected database from which we identified all patients who underwent an intended two-stage revision for PJI of the hip. All patients had a diagnosis of PJI according to the major criteria of the Musculoskeletal Infection Society (MSIS) 2013, a minimum five-year follow-up, and were assessed using the MSIS working group outcome-reporting tool. The outcomes were grouped into ‘successful’ or ‘unsuccessful’. Results. A total of 299 two-stage revision THAs in 289 patients met the inclusion criteria, of whom 258 (86%) proceeded to second-stage surgery. Their mean age was 68.1 years (28 to 92). The median follow-up was 10.7 years (interquartile range (IQR) 6.3 to 15.0). A 91% success rate was seen in those patients who underwent reimplantation, decreasing to 86% when including those who did not proceed to reimplantation. The median duration of postoperative systemic antibiotics following the first stage was five days (IQR 5 to 9). There was no significant difference in outcome between those patients who were treated with antibiotics for ≤ 48 hours (p = 0.961) or ≤ five days (p = 0.376) compared with those who were treated with longer courses. Greater success rates were seen for Gram-positive PJIs (87%) than for Gram-negative (84%) and mixed-Gram PJIs (72%; p = 0.098). Conclusion. Aggressive surgical debridement with a high local concentration of targeted antibiotics at the time of first-stage revision surgery for PJI of the hip, without prolonged systemic antibiotics, provides a high rate of success, responsible antibiotic stewardship, and reduced hospital costs. Cite this article: Bone Joint J 2023;105-B(5):511–517

Aims. The number of revision arthroplasties being performed in the elderly is expected to rise, including revision for infection. The primary aim of this study was to measure the treatment success rate for octogenarians undergoing revision total hip arthroplasty (THA) for periprosthetic joint infection (PJI) compared to a younger cohort. Secondary outcomes were complications and mortality. Methods. Patients undergoing one- or two-stage revision of a primary THA for PJI between January 2008 and January 2021 were identified. Age, sex, BMI, American Society of Anesthesiologists grade, Charlson Comorbidity Index (CCI), McPherson systemic host grade, and causative organism were collated for all patients. PJI was classified as ‘confirmed’, ‘likely’, or ‘unlikely’ according to the 2021 European Bone and Joint Infection Society criteria. Primary outcomes were complications, reoperation, re-revision, and successful treatment of PJI. A total of 37 patients aged 80 years or older and 120 patients aged under 80 years were identified. The octogenarian group had a significantly lower BMI and significantly higher CCI and McPherson systemic host grades compared to the younger cohort. Results. The majority of patients were planned to undergo two-stage revision, although a significantly higher proportion of the octogenarians did not proceed with the second stage (38.7% (n = 12) vs 14.8% (n = 16); p = 0.003). Although there was some evidence of a lower complication rate in the younger cohort, this did not reach statistical significance (p = 0.065). No significant difference in reoperation (21.6% (n = 8) vs 25.0% (n = 30); p = 0.675) or re-revision rate (8.1% (n = 3) vs 16.7% (n = 20); p = 0.288) was identified between the groups. There was no difference in treatment success between groups (octogenarian 89.2% (n = 33) vs control 82.5% (n = 99); p = 0.444). Conclusion. When compared to a younger cohort, octogenarians did not show a significant difference in complication, re-revision, or treatment success rates. However, given they are less likely to be eligible to proceed with second stage revision, consideration should be given to either single-stage revision or use of an articulated spacer to maximize functional outcomes. Cite this article: Bone Joint J 2024;106-B(8):802–807

Aims. One-stage exchange for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) is gaining popularity. The outcome for a repeat one-stage revision THA after a failed one-stage exchange for infection remains unknown. The aim of this study was to report the infection-free and all-cause revision-free survival of repeat one-stage exchange, and to investigate the association between the Musculoskeletal Infection Society (MSIS) staging system and further infection-related failure. Methods. We retrospectively reviewed all repeat one-stage revision THAs performed after failed one-stage exchange THA for infection between January 2008 and December 2016. The final cohort included 32 patients. The mean follow-up after repeat one-stage exchange was 5.3 years (1.2 to 13.0). The patients with a further infection-related failure and/or all-cause revision were reported, and Kaplan-Meier survival for these endpoints determined. Patients were categorized according to the MSIS system, and its association with further infection was analyzed. Results. A total of eight repeat septic revisions (25%) developed a further infection-related failure, and the five-year infection-free survival was 81% (95% confidence interval (CI) 57 to 92). Nine (28%) underwent a further all-cause revision and the five-year all-cause revision-free survival was 74% (95% CI 52 to 88). Neither the MSIS classification of the host status (p = 0.423) nor the limb status (p = 0.366) was significantly associated with further infection-related failure. Conclusion. Repeat one-stage exchange for PJI in THA is associated with a favourable five-year infection-free and all-cause revision-free survival. Notably, the rate of infection control is encouraging when compared with the reported rates after repeat two-stage exchange. The results can be used to counsel patients and help clinicians make informed decisions about treatment. With the available number of patients, further infection-related failure was not associated with the MSIS host or limb status. Cite this article: Bone Joint J 2022;104-B(1):27–33

Aims

The aim of this study was to examine whether socioeconomic status (SES) is associated with a higher risk of infections following total hip arthroplasty (THA) at 30 and 90 days.

Aims. Periprosthetic joint infection (PJI) in total hip arthroplasty in the elderly may occur but has been subject to limited investigation. This study analyzed infection characteristics, surgical outcomes, and perioperative complications of octogenarians undergoing treatment for PJI in a single university-based institution. Methods. We identified 33 patients who underwent treatment for PJIs of the hip between January 2010 and December 2019 using our institutional joint registry. Mean age was 82 years (80 to 90), with 19 females (57%) and a mean BMI of 26 kg/m. 2. (17 to 41). Mean American Society of Anesthesiologists (ASA) grade was 3 (1 to 4) and mean Charlson Comorbidity Index was 6 (4 to 10). Leading pathogens included coagulase-negative Staphylococci (45%) and Enterococcus faecalis (9%). Two-stage exchange was performed in 30 joints and permanent resection arthroplasty in three. Kaplan-Meier survivorship analyses were performed. Mean follow-up was five years (3 to 7). Results. The two-year survivorship free of any recurrent PJI was 72% (95% confidence interval (CI) 56 to 89; 18 patients at risk). There were a total of nine recurrent PJIs at a mean of one year (16 days to eight years), one for the same pathogen as at index infection. One additional surgical site infection was noted at two weeks, resulting in a 69% (95% CI 52 to 86; 17 patients at risk) survivorship free of any infection at two years. There were two additional revisions for dislocations at one month each. As such, the two-year survivorship free of any revision was 61% (95% CI 42 to 80; 12 patients at risk). In addition to the aforementioned revisions, there was one additional skin grafting for a decubitus ulcer, resulting in a survivorship free of any reoperation of 54% (95% CI 35 to 73; ten patients at risk) at two years. Mean Clavien-Dindo score of perioperative complications was two out of five, with one case of perioperative death noted at six days. Conclusion. Octogenarians undergoing surgery for PJI of the hip are at low risk of acute mortality, but are at moderate risk of other perioperative complications. One in two patients will undergo a reoperation within two years, with 70% attributable to recurrent infections. Cite this article: Bone Joint J 2023;105-B(2):135–139

Aims. The prevalence of obesity is increasing substantially around the world. Elevated BMI increases the risk of complications following total hip arthroplasty (THA). We sought to evaluate trends in BMI and complication rates of obese patients undergoing primary THA over the last 30 years. Methods. Through our institutional total joint registry, we identified 15,455 primary THAs performed for osteoarthritis from 1990 to 2019. Patients were categorized according to the World Health Organization (WHO) obesity classification and groups were trended over time. Cox proportional hazards regression analysis controlling for confounders was used to investigate the association between year of surgery and two-year risk of any reoperation, any revision, dislocation, periprosthetic joint infection (PJI), venous thromboembolism (VTE), and periprosthetic fracture. Regression was stratified by three separate groups: non-obese; WHO Class I and Class II (BMI 30 to 39 kg/m. 2. ); and WHO Class III patients (BMI ≥ 40 kg/m. 2. ). Results. There was a significant increase in the proportion of all obesity classes from 1990 to 2019, and the BMI values within each WHO class significantly increased over time. Risk of any reoperation did not change over time among non-obese or WHO Class I/II patients, but increased for WHO Class III patients (hazard ratio (HR) 1.04; p = 0.044). Risk of dislocation decreased over time for non-obese (HR 0.96; p < 0.001) and WHO Class I/II (HR 0.96; p = 0.002) patients, but did not change over time for WHO Class III (HR 0.94; p = 0.073) patients. Risks of any revision and PJI did not change over time for any group. Conclusion. The proportion of patients undergoing THA who are obese has increased dramatically at our institution between 1990 and 2019. Despite BMI values increasing within all WHO classes over time, two-year complication risks have remained stable or decreased in WHO Class I/II patients. However, continued efforts will be required to mitigate risks in the heaviest WHO Class III patients. Cite this article: Bone Joint J 2024;106-B(11):1223–1230

Aims. This study aims to assess the relationship between history of pseudotumour formation secondary to metal-on-metal (MoM) implants and periprosthetic joint infection (PJI) rate, as well as establish ESR and CRP thresholds that are suggestive of infection in these patients. We hypothesized that patients with a pseudotumour were at increased risk of infection. Methods. A total of 1,171 total hip arthroplasty (THA) patients with MoM articulations from August 2000 to March 2014 were retrospectively identified. Of those, 328 patients underwent metal artefact reduction sequence MRI and had minimum two years’ clinical follow-up, and met our inclusion criteria. Data collected included demographic details, surgical indication, laterality, implants used, history of pseudotumour, and their corresponding preoperative ESR (mm/hr) and CRP (mg/dl) levels. Multivariate logistic regression modelling was used to evaluate PJI and history of pseudotumour, and receiver operating characteristic curves were created to assess the diagnostic capabilities of ESR and CRP to determine the presence of infection in patients undergoing revision surgery. Results. The rate of PJI for all identified MoM THAs was 3.5% (41/1,171), with a mean follow-up of 10.9 years (2.0 to 20.4). Of the patients included in the final cohort, 8.2% (27/328) had PJI, with a mean follow-up of 12.2 years (2.3 to 20.4). Among this cohort, 31.1% (102/328) had a history of pseudotumour. The rate of PJI in these patients was 14.7% (15/102), which was greater than those without pseudotumour, 5.3% (12/226) (p = 0.008). Additionally, logistic regression analysis showed an association between history of pseudotumour and PJI (odds ratio 4.36 (95% confidence interval 1.77 to 11.3); p = 0.002). Optimal diagnostic cutoffs for PJI in patients with history of pseudotumour versus those without were 33.1 mm/hr and 24.5 mm/hr for ESR and 7.37 mg/dl and 1.88 mg/dl for CRP, respectively. Conclusion. Patients with history of pseudotumour secondary to MoM THA had a higher likelihood of infection than those without. While suspicion of infection should be high for these patients, ESR and CRP cutoffs published by the European Bone and Joint Infection Society may not be appropriate for patients with a history of pseudotumour, as ESR and CRP levels suggestive of PJI are likely to be higher than for those without a pseudotumour. Additional investigation, such as aspiration, is highly recommended for these patients unless clinical suspicion and laboratory markers are low. Cite this article: Bone Joint J 2024;106-B(6):555–564

Aims. Two-stage exchange revision total hip arthroplasty (THA) performed in case of periprosthetic joint infection (PJI) has been considered for many years as being the gold standard for the treatment of chronic infection. However, over the past decade, there have been concerns about its safety and its effectiveness. The purposes of our study were to investigate our practice, collecting the overall spacer complications, and then to analyze their risk factors. Methods. We retrospectively included 125 patients with chronic hip PJI who underwent a staged THA revision performed between January 2013 and December 2019. All spacer complications were systematically collected, and risk factors were analyzed. Statistical evaluations were performed using the Student's t-test, Mann-Whitney U test, and Fisher's exact test. Results. Our staged exchange practice shows poor results, which means a 42% mechanical spacer failure rate, and a 20% recurrent infection rate over the two years average follow-up period. Moreover, we found a high rate of spacer dislocation (23%) and a low rate of spacer fracture (8%) compared to the previous literature. Our findings stress that the majority of spacer complications and failures is reflecting a population with high comorbid burden, highlighted by the American Society of Anesthesiology grade, Charlson Comorbidity Index, and Lee score associations, as well as the cardiac, pulmonary, kidney, or hepatic chronic conditions. Conclusion. Our experience of a two-stage hip exchange revision noted important complication rates associated with high failure rates of polymethylmethacrylate spacers. These findings must be interpreted in the light of the patient’s comorbidity profiles, as the elective population for staged exchange has an increasing comorbid burden leading to poor results. In order to provide better results for this specific population, our conclusion suggests that comparative strategy studies are required to improve our therapeutic indication. Cite this article: Bone Jt Open 2022;3(6):485–494

Aims. The aims of this study were to determine the incidence and factors for developing periprosthetic joint infection (PJI) following hemiarthroplasty (HA) for hip fracture, and to evaluate treatment outcome and identify factors associated with treatment outcome. Methods. A retrospective review was performed of consecutive patients treated for HA PJI at a tertiary referral centre with a mean 4.5 years’ follow-up (1.6 weeks to 12.9 years). Surgeries performed included debridement, antibiotics, and implant retention (DAIR) and single-stage revision. The effect of different factors on developing infection and treatment outcome was determined. Results. A total of 1,984 HAs were performed during the study period, and 44 sustained a PJI (2.2%). Multiple logistic regression analysis revealed that a higher CCI score (odds ratio (OR) 1.56 (95% confidence interval (CI) 1.117 to 2.187); p = 0.003), peripheral vascular disease (OR 11.34 (95% CI 1.897 to 67.810); p = 0.008), cerebrovascular disease (OR 65.32 (95% CI 22.783 to 187.278); p < 0.001), diabetes (OR 4.82 (95% CI 1.903 to 12.218); p < 0.001), moderate-to-severe renal disease (OR 5.84 (95% CI 1.116 to 30.589); p = 0.037), cancer without metastasis (OR 6.42 (95% CI 1.643 to 25.006); p = 0.007), and metastatic solid tumour (OR 15.64 (95% CI 1.499 to 163.087); p = 0.022) were associated with increasing PJI risk. Upon final follow-up, 17 patients (38.6%) failed initial treatment and required further surgery for HA PJI. One-year mortality was 22.7%. Factors associated with treatment outcome included lower preoperative Hgb level (97.9 g/l (SD 11.4) vs 107.0 g/l (SD 16.1); p = 0.009), elevated CRP level (99.1 mg/l (SD 63.4) vs 56.6 mg/l (SD 47.1); p = 0.030), and type of surgery. There was lower chance of success with DAIR (42.3%) compared to revision HA (66.7%) or revision with conversion to total hip arthroplasty (100%). Early-onset PJI (≤ six weeks) was associated with a higher likelihood of treatment failure (OR 3.5 (95% CI 1.2 to 10.6); p = 0.007) along with patients treated by a non-arthroplasty surgeon (OR 2.5 (95% CI 1.2 to 5.3); p = 0.014). Conclusion. HA PJI initially treated with DAIR is associated with poor chances of success and its value is limited. We strongly recommend consideration of a single-stage revision arthroplasty with cemented components. Cite this article: Bone Jt Open 2022;3(12):924–932

Aims. The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time. Methods. Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces. Results. All animals tolerated surgery well, with preservation of gait mechanics and weightbearing in control individuals. Postoperative in vivo imaging demonstrated predictable evolution of infection with logarithmic signal decay coinciding with abscess formation. Postmortem mCT qualitative volumetric analysis showed high contact area and both cement-bone and cement-implant interdigitation. FE-SEM revealed biofilm formation on the prosthetic head. Conclusion. This study demonstrates the utility of a new, high-fidelity model of in vivo PJI using cemented hip hemiarthroplasty in rats. Inoculation with bioluminescent bacteria allows for non-invasive, real-time monitoring of infection. Cite this article: Bone Joint J 2021;103-B(7 Supple B):9–16

Aims. The purpose of this study was to evaluate unexpected positive cultures in total hip arthroplasty (THA) revisions for presumed aseptic loosening, to assess the prevalence of low-grade infection using two definition criteria, and to analyze its impact on implant survival after revision. Methods. A total of 274 THA revisions performed for presumed aseptic loosening from 2012 to 2016 were reviewed. In addition to obtaining intraoperative tissue cultures from all patients, synovial and sonication fluid samples of the removed implant were obtained in 215 cases (79%) and 101 cases (37%), respectively. Histopathological analysis was performed in 250 cases (91%). Patients were classified as having low-grade infections according to institutional criteria and Musculoskeletal Infection Society (MSIS) International Consensus Meeting (ICM) 2013 criteria. Low-grade infections according to institutional criteria were treated with targeted antibiotics for six weeks postoperatively. Implant failure was defined as the need for re-revision resulting from periprosthetic joint infection (PJI) and aseptic reasons. The mean follow-up was 68 months (26 to 95). Results. Unexpected positive intraoperative samples were found in 77 revisions (28%). Low-grade infection was diagnosed in 36 cases (13%) using institutional criteria and in nine cases (3%) using MSIS ICM 2013 criteria. In all, 41 patients (15%) had single specimen growth of a low-virulent pathogen and were deemed contaminated. Coagulase-negative Staphylococcus and anaerobes were the most commonly isolated bacteria. Implant failure for PJI was higher in revisions with presumed contaminants (5/41, 12%) compared to those with low-grade infections (2/36, 6%) and those with negative samples (5/197, 3%) (p = 0.021). The rate of all-cause re-revision was similar in patients diagnosed with low-grade infections (5/36, 14%) and those with presumed contaminants (6/41, 15%) and negative samples (21/197, 11%) (p = 0.699). Conclusion. Our findings suggest that the presumption of culture contamination in aseptic revision hip arthroplasty may increase the detection of PJI. In this cohort, the presence of low-grade infection did not increase the risk of re-revision. Further studies are needed to assess the relevance of single specimen growth and the benefits of specific postoperative antibiotic regimens. Cite this article: Bone Joint J 2021;103-B(6):1070–1077

Aims. There is a paucity of long-term studies analyzing risk factors for failure after single-stage revision for periprosthetic joint infection (PJI) following total hip arthroplasty (THA). We report the mid- to long-term septic and non-septic failure rate of single-stage revision for PJI after THA. Methods. We retrospectively reviewed 88 cases which met the Musculoskeletal Infection Society (MSIS) criteria for PJI. Mean follow-up was seven years (1 to 14). Septic failure was diagnosed with a Delphi-based consensus definition. Any reoperation for mechanical causes in the absence of evidence of infection was considered as non-septic failure. A competing risk regression model was used to evaluate factors associated with septic and non-septic failures. A Kaplan-Meier estimate was used to analyze mortality. Results. The cumulative incidence of septic failure was 8% (95% confidence interval (CI) 3.5 to 15) at one year, 13.8% (95% CI 7.6 to 22) at two years, and 19.7% (95% CI 12 to 28.6) at five and ten years of follow-up. A femoral bone defect worse than Paprosky IIIA (hazard ratio (HR) 13.58 (95% CI 4.86 to 37.93); p < 0.001) and obesity (BMI ≥ 30 kg/m. 2. ; HR 3.88 (95% CI 1.49 to 10.09); p = 0.005) were significantly associated with septic failure. Instability and periprosthetic fracture were the most common reasons for mechanical failure (5.7% and 4.5%, respectively). The cumulative incidence of aseptic failure was 2% (95% CI 0.4 to 7) at two years, 9% (95% CI 4 to 17) at five years, and 12% (95% CI 5 to 22) at ten years. A previous revision to treat PJI was significantly associated with non-septic failure (HR 9.93 (95% CI 1.77 to 55.46); p = 0.009). At the five-year timepoint, 93% of the patients were alive (95% CI 84% to 96%), which fell to 86% (95% CI 75% to 92%) at ten-year follow-up. Conclusion. Massive femoral bone loss was associated with greater chances of developing a further septic failure. All septic failures occurred within the first five years following the one-stage exchange. Surgeons should be aware of instability and periprosthetic fracture being potential causes of further aseptic revision surgery. Cite this article: Bone Joint J 2021;103-B(7):1247–1253

Aims. We aimed to report the mid- to long-term rates of septic and aseptic failure after two-stage revision surgery for periprosthetic joint infection (PJI) following total hip arthroplasty (THA). Methods. We retrospectively reviewed 96 cases which met the Musculoskeletal Infection Society criteria for PJI. The mean follow-up was 90 months (SD 32). Septic failure was assessed using a Delphi-based consensus definition. Any further surgery undertaken for aseptic mechanical causes was considered as aseptic failure. The cumulative incidence with competing risk analysis was used to predict the risk of septic failure. A regression model was used to evaluate factors associated with septic failure. The cumulative incidence of aseptic failure was also analyzed. Results. There were 23 septic failures at final follow-up, with a cumulative incidence of 14% (95% confidence interval (CI) 8% to 22%) at one year, 18% (95% CI 11% to 27%) at two years, 22% (95% CI 14% to 31%) at five years, and 23% (95% CI 15% to 33%) at ten years. Having at least one positive culture (hazard ratio (HR) 2.38 (interquartile range (IQR) 1.19 to 4.74); p = 0.013), or a positive intraoperative frozen section (HR 2.55 (IQR 1.06 to 6.15); p = 0.037) was significantly associated with septic failure after reimplantation. With dislocation being the most common cause of aseptic revision (5.2%), the cumulative incidence of aseptic failure was 1% (95% CI 0% to 5%) at one year, 6% (95% CI 1% to 8%) at five years, and 8% (95%CI 3% to 17%) at ten years. Conclusion. If there is no recurrent infection in the five years following reimplantation, the chances of further infection thereafter are remote. While the results of a frozen section may be a reliable guide to the timing of reimplantation, intraoperative culture has, currently, only prognostic value. Surgeons should be aware that instability remains a potential indication for further revision surgery. Cite this article: Bone Joint J 2021;103-B(1):79–86

Objectives. The diagnosis of periprosthetic joint infection (PJI) is difficult and requires a battery of tests and clinical findings. The purpose of this review is to summarize all current evidence for common and new serum biomarkers utilized in the diagnosis of PJI. Methods. We searched two literature databases, using terms that encompass all hip and knee arthroplasty procedures, as well as PJI and statistical terms reflecting diagnostic parameters. The findings are summarized as a narrative review. Results. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were the two most commonly published serum biomarkers. Most evidence did not identify other serum biomarkers that are clearly superior to ESR and CRP. Other serum biomarkers have not demonstrated superior sensitivity and have failed to replace CRP and ESR as first-line screening tests. D-dimer appears to be a promising biomarker, but more research is necessary. Factors that influence serum biomarkers include temporal trends, stage of revision, and implant-related factors (metallosis). Conclusion. Our review helped to identify factors that can influence serum biomarkers’ level changes; the recognition of such factors can help improve their diagnostic utility. As such, we cannot rely on ESR and CRP alone for the diagnosis of PJI prior to second-stage reimplantation, or in metal-on-metal or corrosion cases. The future of serum biomarkers will likely shift towards using genomics and proteomics to identify proteins transcribed via messenger RNA in response to infection and sepsis. Cite this article: A. Saleh, J. George, M. Faour, A. K. Klika, C. A. Higuera. Serum biomarkers in periprosthetic joint infections. Bone Joint Res 2018;7:85–93. DOI: 10.1302/2046-3758.71.BJR-2017-0323

Aims. Septic arthritis of the hip often leads to irreversible osteoarthritis (OA) and the requirement for total hip arthroplasty (THA). The aim of this study was to report the mid-term risk of any infection, periprosthetic joint infection (PJI), aseptic revision, and reoperation in patients with a past history of septic arthritis who underwent THA, compared with a control group of patients who underwent THA for OA. Methods. We retrospectively identified 256 THAs in 244 patients following septic arthritis of the native hip, which were undertaken between 1969 and 2016 at a single institution. Each case was matched 1:1, based on age, sex, BMI, and year of surgery, to a primary THA performed for OA. The mean age and BMI were 58 years (35 to 84) and 31 kg/m. 2. (18 to 48), respectively, and 100 (39%) were female. The mean follow-up was 11 years (2 to 39). Results. The ten-year survival free of any infection was 91% and 99% in the septic arthritis and OA groups, respectively (hazard ratio (HR) = 13; p < 0.001). The survival free of PJI at ten years was 93% and 99% in the septic arthritis and OA groups, respectively (HR = 10; p = 0.002). There was a significantly higher rate of any infection at ten years when THA was undertaken within five years of the diagnosis of septic arthritis compared with those in whom THA was undertaken > five years after this diagnosis was made (14% vs 5%, respectively; HR = 3.1; p = 0.009), but there was no significant difference in ten-year survival free of aseptic revision (HR = 1.14; p = 0.485). The mean Harris Hip Scores at two and five years postoperatively were significantly lower in the septic arthritis group compared with the OA group (p = 0.001 for both). Conclusion. There was a ten-fold increased risk of PJI in patients with a history of septic arthritis who underwent THA compared with those who underwent THA for OA with a ten-year cumulative incidence of 7%. The risk of any infection had a strong downward trend as the time interval between the diagnosis of septic arthritis and THA increased, highlighted by a 3.1-fold higher risk when THAs were performed within five years of the diagnosis being made. Cite this article: Bone Joint J 2022;104-B(2):227–234

Aims. One-stage revision hip arthroplasty for periprosthetic joint infection (PJI) has several advantages; however, resection of the proximal femur might be necessary to achieve higher success rates. We investigated the risk factors for resection and re-revisions, and assessed complications and subsequent re-revisions. Methods. In this single-centre, case-control study, 57 patients who underwent one-stage revision arthroplasty for PJI of the hip and required resection of the proximal femur between 2009 and 2018 were identified. The control group consisted of 57 patients undergoing one-stage revision without bony resection. Logistic regression analysis was performed to identify any correlation with resection and the risk factors for re-revisions. Rates of all-causes re-revision, reinfection, and instability were compared between groups. Results. Patients who required resection of the proximal femur were found to have a higher all-cause re-revision rate (29.8% vs 10.5%; p = 0.018), largely due to reinfection (15.8% vs 0%; p = 0.003), and dislocation (8.8% vs 10.5%; p = 0.762), and showed higher rate of in-hospital wound haematoma requiring aspiration or evacuation (p = 0.013), and wound revision (p = 0.008). The use of of dual mobility components/constrained liner in the resection group was higher than that of controls (94.7% vs 36.8%; p < 0.001). The presence and removal of additional metal hardware (odds ratio (OR) = 7.2), a sinus tract (OR 4), ten years’ time interval between primary implantation and index infection (OR 3.3), and previous hip revision (OR 1.4) increased the risk of proximal femoral resection. A sinus tract (OR 9.2) and postoperative dislocation (OR 281.4) were associated with increased risk of subsequent re-revisions. Conclusion. Proximal femoral resection during one-stage revision hip arthroplasty for PJI may be required to reduce the risk of of recurrent or further infection. Patients with additional metalware needing removal or transcortical sinus tracts and chronic osteomyelitis are particularly at higher risk of needing proximal femoral excision. However, radical resection is associated with higher surgical complications and increased re-revision rates. The use of constrained acetabular liners and dual mobility components maintained an acceptable dislocation rate. These results, including identified risk factors, may aid in preoperative planning, patient consultation and consent, and intraoperative decision-making. Cite this article: Bone Joint J 2021;103-B(11):1678–1685

Aims. Modular dual mobility (MDM) acetabular components are often used with the aim of reducing the risk of dislocation in revision total hip arthroplasty (THA). There is, however, little information in the literature about its use in this context. The aim of this study, therefore, was to evaluate the outcomes in a cohort of patients in whom MDM components were used at revision THA, with a mean follow-up of more than five years. Methods. Using the database of a single academic centre, 126 revision THAs in 117 patients using a single design of an MDM acetabular component were retrospectively reviewed. A total of 94 revision THAs in 88 patients with a mean follow-up of 5.5 years were included in the study. Survivorship was analyzed with the endpoints of dislocation, reoperation for dislocation, acetabular revision for aseptic loosening, and acetabular revision for any reason. The secondary endpoints were surgical complications and the radiological outcome. Results. The overall rate of dislocation was 11%, with a six-year survival of 91%. Reoperation for dislocation was performed in seven patients (7%), with a six-year survival of 94%. The dislocations were early (at a mean of 33 days) in six patients, and late (at a mean of 4.3 years) in four patients. There were three intraprosthetic dissociations. An outer head diameter of ≥ 48 mm was associated with a lower risk of dislocation (p = 0.013). Lumbrosacral fusion was associated with increased dislocation (p = 0.004). Four revision THAs (4%) were further revised for aseptic acetabular loosening, and severe bone loss (Paprosky III) at the time of the initial revision was significantly associated with further revision for aseptic acetabular loosening (p = 0.008). Fourteen acetabular components (15%) were re-revised for infection, and a pre-revision diagnosis of reimplantation after periprosthetic joint infection (PJI) was associated with subsequent PJI (p < 0.001). Two THAs had visible metallic changes on the backside of the cobalt chromium liner. Conclusion. When using this MDM component in revision THA, at a mean follow-up of 5.5 years, there was a higher rate of dislocation (11%) than previously reported. The size of the outer bearing was related to the risk of dislocation. There was a low rate of aseptic acetabular loosening. Longer follow-up of this MDM component and evaluation of other designs are warranted. Cite this article: Bone Joint J 2021;103-B(7 Supple B):66–72

Periprosthetic joint infection (PJI) is a devastating complication which can follow a total joint arthroplasty (TJA). Although rare, this ongoing threat undermines the success of TJA, a historically reputable procedure. It has haunted the orthopedic community for decades and several ongoing studies have provided insights and new approaches to effectively battle this multilayered problem

Aims. We hypothesised that the synovial white blood cell (WBC) count in patients with a late periprosthetic joint infection (PJI) of the hip would depend on the duration of a patient’s symptoms, and that the optimal diagnostic threshold would also depend on this period of time. Patients and Methods. The synovial WBC count and percentage of polymorphonuclear cells (%PMN), and the serum CRP and ESR levels obtained > six weeks after primary THA were compared between 50 infected and 88 non-infected THAs, and in patients with symptoms for more than or less than two weeks. Diagnostic thresholds for the synovial WBC count were calculated using area under the curve calculation. Results. The synovial WBC count was significantly higher in patients with symptoms for ≤ two weeks compared with those with symptoms for > two weeks (p = 0.03). The optimal threshold for diagnosing PJI for the synovial WBC count was 5750 cells/µL (sensitivity 94; specificity 100; PPV 100%; NPV 89%; AUC 99%) and 1556 cells/µL (sensitivity 91; specificity 94; PPV 87% and NPV 97%; AUC 95%), respectively. The thresholds for the cut-offs based on duration of symptoms improved the diagnostic performance of this test. Conclusion. This study shows that the diagnostic thresholds for synovial fluid analysis in late periprosthetic infection following THA may depend on duration of symptoms. Cite this article: Bone Joint J 2016;98-B:1355–9

Aims. Advocates of debridement, antibiotics and implant retention (DAIR) in hip periprosthetic joint infection (PJI) argue that a procedure not disturbing a sound prosthesis-bone interface is likely to lead to better survival and functional outcome compared with revision. This case-control study aims were to compare outcome of DAIRs for infected primary total hip arthroplasty (THA) with outcomes following primary THA and two-stage revision of infected primary THAs. Patients and Methods. We retrospectively reviewed all DAIRs, performed for confirmed infected primary hip arthropasty (n = 82) at out institution, between 1997 and 2013. Data recorded included full patient information and type of surgery. Outcome measures included complications, mortality, implant survivorship and functional outcome. Outcome was compared with two control groups matched for gender and age; a cohort of primary THAs (n = 120) and a cohort of two-stage revisions for infection (n = 66). Results. Mean age at DAIR was 69 years (33 to 87) and mean follow-up was eight years (2 to 17; standard deviation (. sd). 5). A total of 52 (63%) of DAIRs were for early PJI (less than six weeks). Greater success in the eradication of infection with DAIR was identified with early PJI, comprising an interval less than a week between onset of symptoms and exchange of modular components with the DAIR procedure. Eradication of infection, complications and re-operation rates were similar in the DAIR and two-stage revision groups. For hips with successful eradication of infection with DAIR, the five-year survival (98%; 95% confidence interval (CI) 94 to 100) was similar to the primary THA group (98%; 95% CI 95 to 100) (n = 43; p = 0.3). The DAIR group had inferior mean Oxford Hip Scores (OHS) (38; 12 to 48) compared with the primary THA group (42; 15 to 48) (p = 0.02) but a significantly better mean OHS compared with the two-stage revision group (31; 0 to 48) (p = 0.008). Patients who required only one DAIR for eradication of infection had a similar mean OHS (41; 20 to 48) to the primary THA group (p = 0.2). Conclusion. The DAIR procedure is associated with a similar complication rate and ability to eradicate infection as two-stage revision. This study emphasises the need for exchange of modular components for improved chances of eradication of infection. This is the first study showing that DAIR is better than a two-stage revision regarding functional outcome. Cite this article: Bone Joint J 2017;99-B:614–22

Objectives. A possible solution for the management of proximal femoral bone loss is a modular femoral endoprosthesis (EPR). Although the outcome of EPRs in tumour surgery has been well described, the outcome of their use in revision hip surgery has received less attention. The aim of this study was to describe the outcome of using EPR for non-neoplastic indications. Methods. A retrospective review of 79 patients who underwent 80 EPRs for non-neoplastic indications was performed, including the rates of complication and survival and the mean Oxford Hip Scores (OHS), at a mean of five years post-operatively. The mean age at the time of surgery was 69 years (28 to 93) and the mean number of previous operations on the hip was 2.4 (0 to 17). The most common indications for EPR implantation were periprosthetic joint infection (PJI) (n = 40), periprosthetic fracture (n = 12) and failed osteosynthesis of a proximal femoral fracture or complex trauma (n = 11). Results. Salvage was achieved in all patients. A total of 25 patients (25 EPRs, 31.6%) had a complication, the most common being infection (n = 9) and dislocation (n = 3). Further surgery was required for 18 EPRs (22%), nine of which were revision procedures. The five year survival of the EPR was 87% (95%CI: 76% to 98%). The mean OHS was 28 (4 to 48). Inferior survival and outcomes were seen in EPRs which were performed for the treatment of infection. However, the eradication of infection was achieved in 33 of the 40 (82.5%) which were undertaken for this indication. Conclusion. We recommend the continued use of proximal femoral EPRs for non-neoplastic indications, including PJI. Cite this article: Bone Joint J 2016;98-B:1463–70

Aims

Current diagnostic tools are not always able to effectively identify periprosthetic joint infections (PJIs). Recent studies suggest that circulating microRNAs (miRNAs) undergo changes under pathological conditions such as infection. The aim of this study was to analyze miRNA expression in hip arthroplasty PJI patients.

Aims

Contemporary outcomes of primary total hip arthroplasties (THAs) with highly cross-linked polyethylene (HXLPE) liners in patients with inflammatory arthritis have not been well studied. This study examined the implant survivorship, complications, radiological results, and clinical outcomes of THA in patients with inflammatory arthritis.

Aims

Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects.

Aims

United Classification System (UCS) B2 and B3 periprosthetic fractures in total hip arthroplasties (THAs) have been commonly managed with modular tapered stems. No study has evaluated the use of monoblock fluted tapered titanium stems for this indication. This study aimed to evaluate the effects of a monoblock stems on implant survivorship, postoperative outcomes, radiological outcomes, and osseointegration following treatment of THA UCS B2 and B3 periprosthetic fractures.

Aims

Periprosthetic hip-joint infection is a multifaceted and highly detrimental outcome for patients and clinicians. The incidence of prosthetic joint infection reported within two years of primary hip arthroplasty ranges from 0.8% to 2.1%. Costs of treatment are over five-times greater in people with periprosthetic hip joint infection than in those with no infection. Currently, there are no national evidence-based guidelines for treatment and management of this condition to guide clinical practice or to inform clinical study design. The aim of this study is to develop guidelines based on evidence from the six-year INFection and ORthopaedic Management (INFORM) research programme.

Aims

Revision total hip arthroplasty in patients with Vancouver type B3 fractures with Paprosky type IIIA, IIIB, and IV femoral defects are difficult to treat. One option for Paprovsky type IIIB and IV defects involves modular cementless, tapered, revision femoral components in conjunction with distal interlocking screws. The aim of this study was to analyze the rate of reoperations and complications and union of the fracture, subsidence of the stem, mortality, and the clinical outcomes in these patients.

Aims

Periprosthetic joint infections (PJIs) with prior multiple failed surgery for reinfection represent a huge challenge for surgeons because of poor vascular supply and biofilm formation. This study aims to determine the results of single-stage revision using intra-articular antibiotic infusion in treating this condition.

Aims

Obesity is associated with an increased risk of hip osteoarthritis, resulting in an increased number of total hip arthroplasties (THAs) performed annually. This study examines the peri- and postoperative outcomes of morbidly obese (MO) patients (BMI ≥ 40 kg/m²) compared to healthy weight (HW) patients (BMI 18.5 to < 25 kg/m²) who underwent a THA using the anterior-based muscle-sparing (ABMS) approach.

Aims

Custom-made partial pelvis replacements (PPRs) are increasingly used in the reconstruction of large acetabular defects and have mainly been designed using a triflange approach, requiring extensive soft-tissue dissection. The monoflange design, where primary intramedullary fixation within the ilium combined with a monoflange for rotational stability, was anticipated to overcome this obstacle. The aim of this study was to evaluate the design with regard to functional outcome, complications, and acetabular reconstruction.

Aims

The aim of this study was to examine the implant accuracy of custom-made partial pelvis replacements (PPRs) in revision total hip arthroplasty (rTHA). Custom-made implants offer an option to achieve a reconstruction in cases with severe acetabular bone loss. By analyzing implant deviation in CT and radiograph imaging and correlating early clinical complications, we aimed to optimize the usage of custom-made implants.

Aims

The aim of this study was to explore the relationship between reason for revision total hip arthroplasty (rTHA) and outcomes in terms of patient-reported outcome measures (PROMs).

Aims

Head-taper corrosion is a cause of failure in total hip arthroplasty (THA). Recent reports have described an increasing number of V40 taper failures with adverse local tissue reaction (ALTR). However, the real incidence of V40 taper damage and its cause remain unknown. The aim of this study was to evaluate the long-term incidence of ALTR in a consecutive series of THAs using a V40 taper and identify potentially related factors.

Aims

With increasing burden of revision hip arthroplasty (THA), one of the major challenges is the management of proximal femoral bone loss associated with previous multiple surgeries. Proximal femoral arthroplasty (PFA) has already been popularized for tumour surgeries. Our aim was to describe the outcome of using PFA in these demanding non-neoplastic cases.

Aims

Femoral cement-in-cement revision is a well described technique to reduce morbidity and complications in hip revision surgery. Traditional techniques for septic revision of hip arthroplasty necessitate removal of all bone cement from the femur. In our two centres, we have been using a cement-in-cement technique, leaving the distal femoral bone cement in selected patients for septic hip revision surgery, both for single and the first of two-stage revision procedures. A prerequisite for adoption of this technique is that the surgeon considers the cement mantle to be intimately fixed to bone without an intervening membrane between cement and host bone. We aim to report our experience for this technique.

Aims

There is evidence that morbidly obese patients have more intra- and postoperative complications and poorer outcomes when undergoing total hip arthroplasty (THA) with the direct anterior approach (DAA). The aim of this study was to determine the efficacy of DAA for THA, and compare the complications and outcomes of morbidly obese patients with nonobese patients.

Aims

As our population ages, the number of octogenarians who will require a total hip arthroplasty (THA) rises. In a value-based system where operative outcomes are linked to hospital payments, it is necessary to assess the outcomes in this population. The purpose of this study was to compare outcomes of elective, primary THA in patients ≥ 80 years old to those aged < 80.

Aims

Total hip arthroplasty (THA) using the direct anterior approach (DAA) is undertaken with the patient in the supine position, creating an opportunity to replace both hips under one anaesthetic. Few studies have reported simultaneous bilateral DAA-THA. The aim of this study was to characterize a cohort of patients selected for this technique by a single, high-volume arthroplasty surgeon and to investigate their early postoperative clinical outcomes.

Aims

The prevalence of ipsilateral total hip arthroplasty (THA) and total knee arthroplasty (TKA) is rising in concert with life expectancy, putting more patients at risk for interprosthetic femur fractures (IPFFs). Our study aimed to assess treatment methodologies, implant survivorship, and IPFF clinical outcomes.

Aims

Use of the direct anterior approach (DAA) for total hip arthroplasty (THA) has increased in recent years due to proposed benefits, including a lower risk of dislocation and improved early functional recovery. This study investigates the dislocation rate in a non-selective, consecutive cohort undergoing THA via the DAA without any exclusion or bias in patient selection based on habitus, deformity, age, sex, or fixation method.

Aims

It has been suggested that the direct anterior approach (DAA) should be used for total hip arthroplasty (THA) instead of the posterior approach (PA) for better early functional outcomes. We conducted a value-based analysis of the functional outcome and associated perioperative costs, to determine which surgical approach gives the better short-term outcomes and lower costs.

Aims

Advances in surgical technique and implant design may influence the incidence and mechanism of failure resulting in revision total hip arthroplasty (rTHA). The purpose of the current study was to characterize aetiologies requiring rTHA, and to determine whether temporal changes existed in these aetiologies over a ten-year period.

Aims

To compare the functional outcome, health-related quality of life (HRQoL), and satisfaction of patients who underwent primary total hip arthroplasty (THA) and a single debridement, antibiotics and implant retention (DAIR) procedure for deep infection, using either the transgluteal or the posterior surgical approach for both procedures.

Aims

The main aims were to identify risk factors predictive of a radiolucent line (RLL) around the acetabular component with an interface bioactive bone cement (IBBC) technique in the first year after THA, and evaluate whether these risk factors influence the development of RLLs at five and ten years after THA.

Aims

To analyse the effectiveness of debridement and implant retention (DAIR) in patients with hip periprosthetic joint infection (PJI) and the relationship to patient characteristics. The outcome was evaluated in hips with confirmed PJI and a follow-up of not less than two years.

The World Health Organization (WHO) and the Centre for Disease Control and Prevention (CDC) recently published guidelines for the prevention of surgical site infection. The WHO guidelines, if implemented worldwide, could have an immense impact on our practices and those of the CDC have implications for healthcare policy in the United States.

Our aim was to review the strategies for prevention of periprosthetic joint infection in light of these and other recent guidelines.

Cite this article: Bone Joint J 2017;99-B(4 Supple B):3–10.

Aims

The purpose of this study was to validate the diagnosis of periprosthetic joint infection (PJI) in the Danish Hip Arthroplasty Register (DHR).

Adverse reaction to wear and corrosion debris is a cause for concern in total hip arthroplasty (THA). Modular junctions are a potential source of such wear products and are associated with secondary pseudotumour formation.

We present a consecutive series of 17 patients treated at our unit for this complication following metal-on-highly cross-linked polyethylene (MoP) THA. We emphasise the risk of misdiagnosis as infection, and present the aggregate laboratory results and pathological findings in this series.

The clinical presentation was pain, swelling or instability. Solid, cystic and mixed soft-tissue lesions were noted on imaging and confirmed intra-operatively. Corrosion at the head–neck junction was noted in all cases. No bacteria were isolated on multiple pre- and intra-operative samples yet the mean erythrocyte sedimentation rate was 49 (9 to 100) and C-reactive protein 32 (0.6 to 106) and stromal polymorphonuclear cell counts were noted in nine cases.

Adverse soft–tissue reactions can occur in MoP THA owing to corrosion products released from the head–neck junction. The diagnosis should be carefully considered when investigating pain after THA. This may avoid the misdiagnosis of periprosthetic infection with an unidentified organism and mitigate the unnecessary management of these cases with complete single- or two-stage exchange.

Cite this article: Bone Joint J 2015;97-B:1024–1030.

We hypothesised that the use of tantalum (Ta) acetabular components in revision total hip arthroplasty (THA) was protective against subsequent failure due to infection. We identified 966 patients (421 men, 545 women and 990 hips) who had undergone revision THA between 2000 and 2013. The mean follow up was 40.2 months (3 months to 13.1 years). The mean age of the men and women was 62.3 years (31 to 90) and 65.1 years (25 to 92), respectively.

Titanium (Ti) acetabular components were used in 536 hips while Ta components were used in 454 hips. In total, 73 (7.3%) hips experienced subsequent acetabular failure. The incidence of failure was lower in the Ta group at 4.4% (20/454) compared with 9.9% (53/536) in the Ti group (p < 0.001, odds ratio 2.38; 95% CI 1.37 to 4.27). Among the 144 hips (64 Ta, 80 Ti) for which revision had been performed because of infection, failure due to a subsequent infection was lower in the Ta group at 3.1% (2/64) compared with 17.5% (14/80) for the Ti group (p = 0.006).

Thus, the use of Ta acetabular components during revision THA was associated with a lower incidence of failure from all causes and Ta components were associated with a lower incidence of subsequent infection when used in patients with periprosthetic joint infection.

Cite this article: Bone Joint J 2015;97-B:45–9.

Advances in the treatment of periprosthetic joint infections of the hip have once more pushed prosthesis preserving techniques into the limelight. At the same time, the common infecting organisms are evolving to become more resistant to conventional antimicrobial agents. Whilst the epidemiology of resistant staphylococci is changing, a number of recent reports have advocated the use of irrigation and debridement and one-stage revision for the treatment of periprosthetic joint infections due to resistant organisms. This review presents the available evidence for the treatment of periprosthetic joint infections of the hip, concentrating in particular on methicillin resistant staphylococci.

Cite this article: Bone Joint J 2014;96-B(11 Suppl A):60–5.

Louis Pasteur once said that: “Fortune favours the prepared mind.” As one of the great scientists who contributed to the fight against infection, he emphasised the importance of being prepared at all times to recognise infection and deal with it. Despite the many scientific discoveries and technological advances, such as the advent of antibiotics and the use of sterile techniques, infection continues to be a problem that haunts orthopaedic surgeons and inflicts suffering on patients.

The medical community has implemented many practices with the intention of preventing infection and treating it effectively when it occurs. Although high-level evidence may support some of these practices, many are based on little to no scientific foundation. Thus, around the world, there is great variation in practices for the prevention and management of periprosthetic joint infection.

This paper summaries the instigation, conduct and findings of a recent International Consensus Meeting on Surgical Site and Periprosthetic Joint Infection.

Cite this article: Bone Joint J 2013;95-B:1450–2.