Citations

Background: Some prior reports of total knee arthroplasty after high tibial osteotomy have shown high rates of aseptic loosening. As such, the goal of this study was to analyze the outcomes of contemporary total knee arthroplasty after high tibial osteotomy, with particular emphasis on survivorship free from aseptic loosening, any revision, and any reoperation; complications; radiographic results; and clinical outcomes. Methods: We retrospectively reviewed 207 patients who underwent 231 total knee arthroplasties using cemented prostheses after high tibial osteotomy from 2000 to 2012 through our total joint registry: 87% were after a closing-wedge osteotomy and 13% were after an opening-wedge osteotomy. The mean follow-up from total knee arthroplasty was 8 years. At the time of the total knee arthroplasty, the mean age was 64 years and the mean body mass index was 31 kg/m 2 . The majority of total knee arthroplasties had a posterior-stabilized design (93%), and 4% had a varus-valgus constraint design. Tibial stems were utilized in 8% of cases. Bivariate and multivariate Cox regression analyses were utilized to analyze risk factors for poorer survival. Results: At 10 years, survivorship free from aseptic loosening was 97%, survivorship free from any revision was 90%, and survivorship free from any reoperation was 85%. Fifteen patients (15 total knee arthroplasties [6%]) underwent aseptic revision, most commonly for instability (3%), aseptic loosening (2%), and periprosthetic fracture (1%). On bivariate analysis, patient age of <60 years was a significant risk factor for poorer revision-free survival (hazard ratio, 2.9; p = 0.02); on multivariate analysis, younger age was the only significant risk factor for revision (p = 0.04). There were 14 complications (6%), the most common being a manipulation under anesthesia in 9 cases (4%). No unrevised total knee arthroplasties had definitive radiographic evidence of loosening. Knee Society scores improved from a mean preoperative score of 59 points to a mean postoperative score of 93 points (p < 0.001). Conclusions: Contemporary total knee arthroplasty with a cemented prosthesis after high tibial osteotomy demonstrated excellent long-term durability, with 10-year survivorship free from aseptic loosening of 97%. There was reliable improvement in clinical outcomes, but perfect knee balance was sometimes challenging, as reflected by a 4% prevalence of manipulation under anesthesia and a 3% prevalence of revision for instability. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

AimsThere is little literature about total knee arthroplasty (TKA) after distal femoral osteotomy (DFO). Consequently, the purpose of this study was to analyze the outcomes of TKA after DFO, with particular emphasis on: survivorship free from aseptic loosening, revision, or any re-operation; complications; radiological results; and clinical outcome.Patients and MethodsWe retrospectively reviewed 29 patients (17 women, 12 men) from our total joint registry who had undergone 31 cemented TKAs after a DFO between 2000 and 2012. Their mean age at TKA was 51 years (22 to 76) and their mean body mass index 32 kg/m2(20 to 45). The mean time between DFO and TKA was ten years (2 to 20). The mean follow-up from TKA was ten years (2 to 16). The prostheses were posterior-stabilized in 77%, varus-valgus constraint (VVC) in 13%, and cruciate-retaining in 10%. While no patient had metaphyseal fixation (e.g. cones or sleeves), 16% needed a femoral stem.ResultsThe ten-year survivorship was 95% with aseptic loosening as the endpoint, 88% with revision for any reason as the endpoint, and 81% with re-operation for any reason as the endpoint. Three TKAs were revised for instability (n = 2) and aseptic tibial loosening (n = 1). No femoral component was revised for aseptic loosening. Patients under the age of 50 years were at greater risk of revision for any reason (hazard ratio 7; p = 0.03). There were two additional re-operations (6%) and four complications (13%), including three manipulations under anaesthetic (MUA; 10%). The Knee Society scores improved from a mean of 50 preoperatively (32 to 68) to a mean of 93 postoperatively (76 to 100; p < 0.001).ConclusionA cemented posterior-stabilized TKA has an 88% ten-year survivorship with revision for any reason as the endpoint. No femoral component was revised for aseptic loosening. Patients under the age of 50 years have a greater risk of revision. The clinical outcome was significantly improved but balancing the knee was challenging in 13% of TKAs requiring VVC. Overall, 10% of TKAs needed an MUA, and 6% of TKAs were revised for instability. Cite this article: Bone Joint J 2019;101-B:660–666.

Aims Modular dual-mobility constructs reduce the risk of dislocation after revision total hip arthroplasty (THA). However, questions about metal ions from the cobalt-chromium (CoCr) liner persist, and are particularly germane to patients being revised for adverse local tissue reactions (ALTR) to metal. We determined the early- to mid-term serum Co and Cr levels after modular dual-mobility components were used in revision and complex primary THAs, and specifically included patients revised for ALTR. Patients and Methods Serum Co and Cr levels were measured prospectively in 24 patients with a modular dual-mobility construct and a ceramic femoral head. Patients with CoCr heads or contralateral THAs with CoCr heads were excluded. The mean age was 63 years (35 to 83), with 13 patients (54%) being female. The mean follow-up was four years (2 to 7). Indications for modular dual-mobility were prosthetic joint infection treated with two-stage exchange and subsequent reimplantation (n = 8), ALTR revision (n = 7), complex primary THA (n = 7), recurrent instability (n = 1), and periprosthetic femoral fracture (n = 1). The mean preoperative Co and Cr in patients revised for an ALTR were 29.7 μg/l (2 to 146) and 21.5 μg/l (1 to 113), respectively. Results Mean Co and Cr levels were 0.30 μg/l and 0.76 μg/l, respectively, at the most recent follow-up. No patient had a Co level ≥ 1 μg/l. Only one patient had a Cr level ≥ 1 μg/l. That patient’s Cr level was 12 μg/l at 57 months after revision THA for ALTR (and decreased ten-fold from a preoperative Cr of 113 μg/l). Conclusion At a mean of four years, no patient with a modular dual-mobility construct and ceramic femoral head had elevated Co levels, including seven patients revised specifically for ALTR. While further studies are required, we support the selective use of a modular dual-mobility construct in revision and complex primary THAs for patients at high risk for instability. Cite this article: Bone Joint J 2019;101-B(6 Supple B):57–61.

Aims Tranexamic acid (TXA) has been shown to significantly reduce transfusion rates in primary total hip arthroplasties (THAs), but high-quality evidence is limited in the revision setting. The purpose of the current study was to compare the rate of blood transfusions and symptomatic venous thromboembolic events (VTEs) in a large cohort of revision THAs treated with or without intravenous (IV) TXA. Patients and Methods We performed a retrospective review of 3264 revision THAs (2645 patients) between 2005 and 2014, of which 1142 procedures received IV TXA (1 g at incision and 1 g at closure). The mean age in the revision group with TXA was 65 years (28 to 95), with 579 female patients (51%). The mean age in the revision group treated without TXA was 67 years (21 to 98), with 1160 female patients (55%). Outcomes analyzed included rates of transfusion and symptomatic VTEs between procedures undertaken with and without TXA. These comparisons were performed for the overall cohort, as well as within cases subcategorized for aseptic or septic aetiologies. A propensity score was developed to minimize bias between groups and utilized age at revision THA, sex, body mass index, American Society of Anesthesiologists (ASA) score, preoperative anticoagulation, and year of surgery. Results Tranexamic acid significantly and substantially reduced the rate of blood transfusions after revision THA overall from 54% to 26% (p < 0.001; adjusted relative risk (RR) 1.6; 95% confidence interval (CI) 1.3 to 1.9), with a significant reduction in both aseptic (49% to 18%; p < 0.001) and septic (73% to 53%; p = 0.04) revisions. The rate of VTE was minimal overall, with three events (0.3%) in the TXA group and four events (0.2%) in the non-TXA group. There were no significant differences in VTE rates based on TXA use or aetiology of revision. Conclusion Intravenous TXA significantly reduced transfusion rates during all-cause revision THAs, including a subgroup analysis of both aseptic and septic cohorts. Adjusted risk using propensity modelling showed no statistical difference in rates of VTEs between either group. Cite this article: Bone Joint J 2019;100-B(6 Supple B):104–109.

e17500 Background: Metastatic head and neck cancer is a diagnosis with poor prognosis and very little in terms of available active therapy. Until recently the mainstay of therapy was chemotherapy with or without cetuximab. The regimen of cetuximab (C), platinum (P) and 5FU has a response rate(RR) of 36% in the first line setting, and a PFS of 5.6 months and OS of 10.1 months. In the setting of post first line therapy immunotherapeutic agents (IO) have average RR of 15% and median OS of 8 months. Methods: We studied all patients with metastatic or recurrent head and neck cancer who were treated with an IO at our institution between May 2016 and July 2018 evaluating their entire history of therapy. 19 patient were treated with IO at our institution in the designated period of whom 9 received nivolumab (N) and 10 received pembrolizumab ( P ). Patients treated on trials were excluded. Patients who received less than 1 cycle of therapy were also excluded. 7 of the 19 patients received an IO in the first line setting after being refractory or resistant to platinum containing definitive therapy, 7 received the IO after a cetuximab (C) containing first line regimen, 1 patient received IO in second line but was naïve to C and 4 received IO in the third line setting. Results: 3 of 19 patients treated with IO had partial response, there were no complete responses, 6 patients had stable disease as their best response and 10 patients progressed at the time of their first evaluation. 11 of 19 patients received additional therapy post IO. 10 patients received taxane based therapy 5 of whom the taxane was combined with C. Of the 5 patients who received a taxane and C combination 2 had CR, 2 had PR and one had PD. Of the 5 who received other taxane regimens, 1 had PR 1 had SD and 1 had PD, 2 expired prior to their first evaluation. The patient who received a non taxane regimen all had progressive disease. Of the 4 responding patients to C regimens 1 had SD during IO therapy and 3 had PD. The longest response duration to a C regimen post IO was 628 days. Conclusions: We observe an unusual response rate among patients treated with a combination of taxanes and cetuximab after IO therapy. This finding may relate to a modifying effect of IO on sensitivity to subsequent therapy. This observation merits further investigation.

4087 Background: The management of CCA has evolved as targeted and immune checkpoint inhibitor (ICPI) therapies have emerged. We used comprehensive genomic profiling (CGP) to characterize the genomic alterations (GA) that have potential to personalize therapy for CCA. Methods: 3634 CCA underwent hybrid capture based CGP on 0.8-1.1 Mb of the coding genome to identify GAs in exons and select introns in up to 404 genes, TMB, microsatellite status (MSI) and % monoallelic genome (gLOH). PD-L1 expression was determined by IHC (Dako 22C3). Results: 52% of CCA were female with a median age of 62 years (range 16 - > 89). The most common biopsy sites were liver (74%), lymph node (4%), bile duct (3.3%), and lung (2%). MSI-high was rare (1%), 118 and 47 cases had TMB > 10 and > 20 mut/mb respectively. Of the latter, 51% (24/47) were MSI-H. PD-L1 amplification (AMP) was present in 0.27%. Of 490 CCA tested, 43 (9%) were positive for PD-L1 expression. 11% of cases had gLOH > 16%, only 2 cases had both TMB > 20 and gLOH > 16%. GA were most common in TP53 (31%), CDKN2A (29%), KRAS (20%) and ARID1A (17%). Potentially targetable GAs included FGFR2 (11%, 85% fusions), BRAF (5%, 50% V600E), ERBB2 (5%, 72% AMP), MET (2%, 90% AMP), EGFR (0.52%) and rarer ( < 0.5%) FGFR3, RET, FGFR1, ALK, and ROS1 fusions. The FGFR2 fusions had 128 unique 3’ partner genes including BICC1 (26%), CCDC6 (3.2%), AHCYL1 (2.6%) and KIAA1217 (2.6%). FGFR2 fusions occurred in a mutually exclusive fashion from high gLOH (p < 0.002), but not high TMB. GA in IDH1 (15%) were mutually exclusive of FGFR2 fusions (p < 1e-13), but co-occurred with PBRM1 GA (23%, p < 1e-21), ARID1A (26% p < 1e-10). IDH1 GA had gLOH similar to the overall CCA population but were enriched for low TMB (p < 1e-3). Conclusions: Nearly 20% of CCA cases harbor targetable kinase GA, half of which were FGFR2 fusions. Independently, an additional 10% (gLOH) and 1% (high TMB, MSI and/or PD-L1 AMP) may benefit from PARP inhibitors and ICPI respectively. Independently, co-mutation of IDH1 and PBRM1/ARID1A defines a class of CCA that warrants further investigation for sensitivity to PARP inhibitors and may serve as a paradigm for other tumors (ie. gliomas) with a similar co-occurrence landscape.

Abstract Background Immune-related adverse events (irAEs) have emerged as a serious clinical issue in the use of immune checkpoint inhibitors (ICIs). Risk factors for irAEs remain controversial. Therefore, we studied sex differences in irAEs in patients treated with anti-programmed cell death protein 1 (PD-1) therapy. Materials and Methods All patients with metastatic melanoma and non-small cell lung cancer (NSCLC) treated with anti-PD-1 therapy at Mayo Clinic Rochester and Florida from 2015 to 2018 were reviewed. Kaplan-Meier method and log-rank test was used for time-to-event analysis. Results In 245 patients with metastatic melanoma, premenopausal women were more likely to experience irAEs (all grades) compared with postmenopausal women and men (67% vs. 60% vs. 46%), primarily because of an increase in endocrinopathies (33% vs. 12% vs. 10%, respectively). In patients with NSCLC (231 patients), women (all ages) were also more likely to develop irAEs of all grades (48% vs. 31%). Women with NSCLC were more likely to develop pneumonitis (11% vs. 4%) and endocrinopathies (14% vs. 5%). No differences in grade ≥3 toxicities were seen across sexes in both cohorts, but women were more likely to receive systemic steroids for the treatment of irAEs compared with men. Better progression-free-survival was observed in women with NSCLC and irAEs (10 months vs. 3.3 months) compared with women without irAEs. Conclusion Women with metastatic melanoma and NSCLC are more likely to experience irAEs compared with men. We also observed differences between sexes in the frequency of certain irAEs. Larger studies are needed to investigate the mechanisms underlying these associations. Implications for Practice The results of this study suggest that women may be at a higher risk for immune-related adverse events (irAEs) compared with men when treated with anti-programmed cell death protein 1 therapy. In addition, women were more likely to develop certain irAEs, including endocrinopathies and pneumonitis. Close follow-up of women undergoing treatment with immune checkpoint inhibitors will allow clinicians to diagnose these treatment-related complications early, potentially reducing their associated morbidity and mortality. In addition, a possible association between irAEs and response to therapy was observed.

Background: Cementation of a constrained liner is a viable option for treating instability after total hip arthroplasty (THA) when the acetabular component is well fixed and well aligned. However, concerns regarding long-term mechanical failure and recurrent instability remain. The aim of this study was to evaluate the long-term survivorship, complications, and clinical and radiographic outcomes of constrained polyethylene liners cemented into well-fixed acetabular components at the time of revision THA. Methods: We identified 125 cases in which a constrained liner of 1 design was cemented into a retained, osseointegrated acetabular component during revision THA between 1998 and 2006. The mean patient age at revision was 70 years. Mean follow-up was 7 years. Survivorship data, risk of instability, and clinical and radiographic outcomes were analyzed. Results: Survivorship free from revision for instability was 86% at 5 years and 81% at 10 years. Survivorship free from aseptic acetabular component revision was 78% at 5 years and 65% at 10 years, with the most common failure mechanism being dissociation of the constrained liner from the acetabular component. Survivorship free from revision for any reason was 76% at 5 years and 60% at 10 years. The most common complications were instability and periprosthetic joint infection, with cumulative incidences at 7 years of 18% and 11%, respectively. Harris hip scores did not significantly improve. Cup position did not affect implant survivorship or risk of dislocation. Conclusions: Cementing a constrained liner into a retained acetabular shell at the time of revision THA has durable long-term results, with 8 in 10 patients free from instability at 10 years. Aseptic acetabular survivorship was worse (65%) at 10 years, primarily due to dissociation of the constrained liner from the acetabular component. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Background: Polyethylene (PE) liner and femoral head exchange is commonly used to treat periprosthetic osteolysis associated with PE wear after total hip arthroplasty (THA). The purpose of our study was to determine long-term implant survivorship, risk factors for mechanical failure, clinical outcomes, and complications following PE liner and head exchange. Methods: We identified 116 hips in 110 patients treated with PE liner and head exchange from 1993 to 2004. There were 64 women (58%) in the series, the mean age at revision surgery was 58 years, and the mean follow-up was 11 years (range, 2 to 23 years). Radiographic review determined the location and size of osteolytic defects before the revision surgery. Implant survivorship was determined using Kaplan-Meier survival analysis. Cox regression analysis was used to determine factors that were predictive of failure. Results: Implant survivorship free of repeat revision for any cause was 91% (95% confidence interval [CI] = 86% to 96%) at 5 years, 81% (95% CI = 74% to 90%) at 10 years, and 69% (95% CI = 55% to 84%) at 15 years. Reasons for repeat revision included aseptic acetabular loosening in 5 hips (4%) and subsequent wear of conventional PE with osteolysis in 5 hips (4%). No patient who underwent revision with highly cross-linked PE subsequently had a repeat revision due to wear. The absolute risk of acetabular component loosening was 23% for patients with osteolysis in 3 zones, 40% for those with osteolysis involving more than half the cup circumference, and 21% for those with osteolytic defects of >600 mm 2 . The mean Harris hip score improved from 77 before the PE liner and head exchange to 87 after it (p < 0.001). The most common complication was dislocation, which occurred in 19 hips (16%). Conclusions: PE liner and head exchange provides acceptable long-term implant survivorship with good clinical outcomes. Complications are not uncommon, and steps should be taken to mitigate hip instability. Acetabular revision may be considered when in situ components have a poor track record or are malpositioned, or when preoperative radiographs demonstrate large osteolytic defects threatening cup fixation. Use of highly cross-linked PE at revision was protective against subsequent PE wear and osteolysis, although this did not reach significance. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.