Citations

Aims The aim of this study was to compare the ability of tantalum, 3D porous titanium, antibiotic-loaded bone cement, and smooth titanium alloy to inhibit staphylococci in an in vitro environment, based on the evaluation of the zone of inhibition (ZOI). The hypothesis was that there would be no significant difference in the inhibition of methicillin-sensitive or methicillin-resistant Staphylococcus aureus (MSSA/MRSA) between the two groups. Methods A total of 30 beads made of three different materials (tantalum/3D porous titanium and smooth titanium alloy) were bathed for one hour in a solution of 1 g vancomycin in 20 ml of sterile water for injection (bath concentration: 50 mg/mL). Ten 1 cm3 cylinders of antibiotic-loaded cement were also created by mixing standard surgical cement with 1 g of vancomycin in standardized sterile moulds. The cylinders were then placed on agar plates inoculated with MSSA and MRSA. The ZOIs were measured each day and the cylinders were transferred onto a new inoculated plate. Results For MSSA and MRSA, no inhibitory effect was found in the control group, and antibiotic-loaded smooth titanium alloy beads showed a short inhibitory effect until day 2. For MSSA, both tantalum and 3D porous titanium beads showed significantly larger mean ZOIs than cement beads (all p < 0.01) each day until day 7 for tantalum and until day 3 for 3D porous titanium. After six days, antibiotic-loaded cement had significantly larger mean ZOIs than the 3D porous titanium (p = 0.027), but no significant difference was found with tantalum (p = 0.082). For MRSA, both tantalum and 3D porous titanium beads had significantly larger mean ZOIs than antibiotic-loaded cement each day until day 6 for tantalum (all p < 0.01) and until day 3 for 3D porous titanium (all p < 0.04). Antibiotic-loaded cement had significantly larger mean ZOIs than tantalum and 3D porous titanium from day 7 to 9 (all p < 0.042). Conclusion These results show that porous metal implants can deliver local antibiotics over slightly varying time frames based on in vitro analysis. Cite this article: Bone Joint J 2020;102-B(6 Supple A):158–162.

Aims Arthrodesis is rarely used as a salvage procedure for patients with a chronically infected total knee arthroplasty (TKA), and little information is available about the outcome. The aim of this study was to assess the reliability, durability, and safety of this procedure as the definitive treatment for complex, chronically infected TKA, in a current series of patients. Methods We retrospectively identified 41 patients (41 TKAs) with a complex infected TKA, who were treated between 2002 and 2016 using a deliberate, two-stage knee arthrodesis. Their mean age was 64 years (34 to 88) and their mean body mass index (BMI) was 39 kg/m2 (25 to 79). The mean follow-up was four years (2 to 9). The extensor mechanism (EM) was deficient in 27 patients (66%) and flap cover was required in 14 (34%). Most patients were host grade B (56%) or C (29%), and limb grade 3 (71%), according to the classification of McPherson et al. A total of 12 patients (29%) had polymicrobial infections and 20 (49%) had multi-drug resistant organisms; fixation involved an intramedullary nail in 25 (61%), an external fixator in ten (24%), and dual plates in six (15%). Results Survivorship free from amputation, persistent infection, and reoperation, other than removal of an external fixator, at five years was 95% (95% confidence interval (CI) 89% to 100%), 85% (95% CI 75% to 95%), and 64% (95% CI 46% to 82%), respectively. Reoperation, other than removal of an external fixator, occurred in 13 patients (32%). After the initial treatment, radiological nonunion developed in ten knees (24%). Nonunion was significantly correlated with persistent infection (p = 0.006) and external fixation (p = 0.005). Of those patients who achieved limb salvage, 34 (87%) remained mobile and 31 (79%) had ‘absent’ or ‘minimal’ pain ratings. Conclusion Knee arthrodesis using a two-stage protocol achieved a survivorship free from amputation for persistent infection of 95% at five years with 87% of patients were mobile at final follow-up. However, early reoperation was common (32%). This is not surprising as this series included worst-case infected TKAs in which two-thirds of the patients had a disrupted EM, one-third required flap cover, and most had polymicrobial or multi-drug resistant organisms. Cite this article: Bone Joint J 2020;102-B(6 Supple A):170–175.

AimsMetaphyseal fixation during revision total knee arthroplasty (TKA) is important, but potentially difficult when using historical designs of cone. Material and manufacturing innovations have improved the size and shape of the cones which are available, and simplified the required bone preparation. In a large series, we assessed the implant survivorship, radiological results, and clinical outcomes of new porous 3D-printed titanium metaphyseal cones featuring a reamer-based system.MethodsWe reviewed 142 revision TKAs in 139 patients using 202 cones (134 tibial, 68 femoral) which were undertaken between 2015 and 2016. A total of 60 involved tibial and femoral cones. Most cones (149 of 202; 74%) were used for Type 2B or 3 bone loss. The mean age of the patients was 66 years (44 to 88), and 76 (55 %) were female. The mean body mass index (BMI) was 34 kg/m2(18 to 60). The patients had a mean of 2.4 (1 to 8) previous operations on the knee, and 68 (48%) had a history of prosthetic infection. The mean follow-up was 2.4 years (2 to 3.6).ResultsSurvivorship free of cone revision for aseptic loosening was 100% and survivorship free of any cone revision was 98%. Survivorships free of any revision and any reoperation were 90% and 83%, respectively. Five cones were revised: three for infection, one for periprosthetic fracture, and one for aseptic tibial loosening. Radiologically, three unrevised femoral cones appeared loose in the presence of hinged implants, while the remaining cones appeared stable. All cases of cone loosening occurred in patients with Type 2B or 3 defects. The mean Knee Society score (KSS) improved significantly from 50 (0 to 94) preoperatively to 87 (72 to 94) (p < 0.001). Three intraoperative fractures with cone impaction (two femoral, one tibial) healed uneventfully.ConclusionNovel 3D-printed titanium cones, with a reamer-based system, yielded excellent early survivorship and few complications in patients with severe bone loss undergoing difficult revision TKA. The diversity of cone options, relative ease of preparation, and outcomes rivalling those of previous designs of cone support their continued use. Cite this article: Bone Joint J 2020;102-B(6 Supple A):107–115.

Aims Metaphyseal cones with cemented stems are frequently used in revision total knee arthroplasty (TKA). However, if the diaphysis has been previously violated, the resultant sclerotic canal can impair cemented stem fixation, which is vital for bone ingrowth into the cone, and long-term fixation. We report the outcomes of our solution to this problem, in which impaction grafting and a cemented stem in the diaphysis is combined with an uncemented metaphyseal cone, for revision TKA in patients with severely compromised bone. Methods A metaphyseal cone was combined with diaphyseal impaction grafting and cemented stems for 35 revision TKAs. There were two patients with follow-up of less than two years who were excluded, leaving 33 procedures in 32 patients in the study. The mean age of the patients at the time of revision TKA was 67 years (32 to 87); 20 (60%) were male. Patients had undergone a mean of four (1 to 13) previous knee arthroplasty procedures. The indications for revision were aseptic loosening (80%) and two-stage reimplantation for prosthetic joint infection (PJI; 20%). The mean follow-up was four years (2 to 11). Results Survival free from revision of the cone/impaction grafting construct due to aseptic loosening was 100% at five years. Survival free from any revision of the construct and free from any reoperation were 92% and 73% at five years, respectively. A total of six patients (six TKAs, 17%) required a further revision, four for infection or wound issues, and two for periprosthetic fracture. Radiologically, one unrevised TKA had evidence of loosening which was asymptomatic. In all unrevised TKAs the impacted diaphyseal bone graft appeared to be incorporated radiologically. Conclusion When presented with a sclerotic diaphysis and substantial metaphyseal bone loss, this technique combining diaphyseal impaction grafting with a metaphyseal cone provided near universal success in relation to implant fixation. Moreover, radiographs revealed incorporation of the bone graft and biological fixation of the cone. While long-term follow-up will be important, this technique provides an excellent option for the management of complex revision TKAs. Cite this article: Bone Joint J 2020;102-B(6 Supple A):116–122.

Background: Many surgeons are reluctant to use a constrained liner at the time of acetabular component revision because of concerns that doing so might result in early acetabular component loosening related to high bone-implant interface stresses transmitted from the constrained liner. We hypothesized that, with appropriate initial implant stabilization using highly porous acetabular components with robust supplemental screw fixation, constrained liners could be safely used at the time of acetabular revision. Methods: We retrospectively identified 148 revision total hip arthroplasties (THAs) in which a constrained liner of 1 design was cemented into a newly placed highly porous acetabular component fixed with supplemental screws (mean, 5 screws). The mean age at the time of revision THA was 69 years, and 68% of the patients were female. The most common indications for revision were 2-stage reimplantation (33%), recurrent dislocation (30%), and aseptic loosening of the acetabular component (22%) or both the acetabular and femoral components (9%). The mean duration of follow-up was 7 years. Results: There were no failures at the bone-implant interface. No cases of acetabular metal shell loosening were identified on radiographic analysis. The 10-year survival rates with acetabular revision and any reoperation as the end points were 75% and 67%, respectively. Overall, 33 hips (22%) required revision or reoperation because of infection or wound complications (n = 12), dislocation or mechanical failure of the constrained liner (n = 11), periprosthetic femoral fracture (n = 4), femoral loosening (n = 3), or other reasons (n = 3). The 10-year survival rate with re-revision for instability as the end point was 88% overall, which was similar to the 85% 10-year survival rate with re-revision for instability as the end point among hips that were specifically revised because of instability during index revision THA (p = 0.9). Conclusions: Implanting a constrained liner at the time of acetabular revision in high-risk patients resulted in no cases of aseptic metal acetabular component loosening in this large series. This finding is likely related to the fact that a highly porous acetabular component was utilized with robust supplemental screw fixation in each case. Such information is valuable as these data favor a paradigm shift when compared with some traditionally held tenets. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Background: The periacetabular region is a common location for metastatic disease. Although large lytic acetabular defects are commonly treated with a hip arthroplasty with a cemented component according to a Harrington-style reconstruction, the use of highly porous uncemented tantalum acetabular components has been described. Currently, there are no direct comparisons of these reconstructive techniques. The purpose of this study was to compare the outcomes of the Harrington technique and tantalum acetabular component reconstruction for periacetabular metastases. Methods: From 2 tertiary sarcoma centers, we retrospectively reviewed 115 patients (70 female and 45 male) with an acetabular metastatic defect who had been treated between 2002 and 2015 with a total hip arthroplasty using either the cemented Harrington technique (78 patients) or a tantalum acetabular reconstruction (37 patients). The mean patient age was 61 years, and the most common Eastern Cooperative Oncology Group status was 3 (39 patients). The mean follow-up for surviving patients was 4 years. Results: An additional surgical procedure was performed in 24 patients (21%). Harrington-style reconstructions were more likely to require a reoperation compared with tantalum reconstructions (hazard ratio [HR], 4.59; p = 0.003). The acetabular component was revised in 13 patients (11%); 5 patients (4%) underwent revisions that were due to loosening of the acetabular component. The 10-year cumulative incidence of revision of the acetabular component for loosening was 9.6% in the Harrington group and 0% in the tantalum group (p = 0.09). The mean Harris hip score significantly improved following reconstruction (31 to 67 points; p < 0.001), with no significant difference (p = 0.29) between groups. Conclusions: In patients with periacetabular metastatic disease treated with total hip arthroplasty, an acetabular reconstruction strategy utilizing highly porous tantalum acetabular components and augments successfully provided patients with a more durable construct with fewer complications compared with the cemented Harrington-style technique. Levels of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

7523 Background: tALL is a recently appreciated but poorly defined clinical entity. We define tALL as any prior exposure to cytotoxic chemotherapy and/or radiation for another malignancy, and we report a comparative analysis of characteristics, cytogenetics and outcomes for this subset among a modern unselected ALL cohort from the Mayo Clinic Cancer Center (MCCC). Methods: We performed a systematic search in the 3-site MCCC registry and included all patients (pts) diagnosed and received at least 1 cycle of ALL-directed therapy and/or underwent allogeneic transplantation (AlloHCT) between 2008-2018. Comparisons of characteristics between tALL and dnALL were made using a Wilcoxon rank sum test (continuous variables) and Fisher’s exact test (categorical variables). Time-to-event variables were compared using unadjusted Cox proportional hazards regression models. Results: 431 ALL pts were identified during the study period, including n = 69 (16%) classified as tALL. Median follow-up from diagnosis was 2.3 years (range 0-18 years). The most common prior malignancies among tALL pts were Breast (24.6%), Lymphoma (15.9%), Myeloid (15.9%), GU/GYN (14.5%) and Myeloma (11.6%). In comparison to dnALL, pts with tALL were significantly older (63.2 vs 45.2 years, P < 0.001), more often female (65.2% vs 39.8%, P < 0.001), less frequently Hispanic (3.5% vs 13.1%, P = 0.042); more often of B-lineage (92.8% vs 81.8%, P = 0.022). On review of cytogenetics, tALL pts more often had hypodiploidy/near triploidy (Ho/Tr) (21.7% vs 4.1%, P < 0.001), more often had monosomal (MDS-like) (33.3% vs 12.4%, P = 0.0047) and complex karyotype (38% vs 17.3%, P = 0.0069). Importantly, incidence of BCR/ABL-positive (Ph+) ALL was not significantly different. Latency period between exposure to prior cancer therapy and development of tALL was significantly longer for Ph+ compared to Ph-negative ALL (median 9 vs. 4 years, P = 0.007). Patients with tALL had a 3-year OS after diagnosis of 37% [vs 59.7% for dnALL (HR death 1.86, 95% CI 1.31-2.65, P < 0.001)]. However, the two groups did not differ significantly regarding occurrence of AlloHCT (HR = 0.91, 95% CI 0.63-1.31, P = 0.61) or post-AlloHCT survival (HR = 1.29, 95% CI 0.75-2.23, P = 0.35). Conclusions: Therapy-related ALL represents an important & unique clinical entity with poor prognosis & adverse cytogenetic features. Ph+ tALL has a longer latency and similar frequency in both tALL and dnALL. AlloHCT appears to be an appropriate treatment strategy, possibly abrogating the poor prognosis of tALL.

PURPOSE There is no consensus on the best choice of an alternative donor (umbilical cord blood [UCB], haploidentical, one-antigen mismatched [7/8]–bone marrow [BM], or 7/8-peripheral blood [PB]) for hematopoietic cell transplantation (HCT) for patients lacking an HLA-matched related or unrelated donor. METHODS We report composite end points of graft-versus-host disease (GVHD)–free relapse-free survival (GRFS) and chronic GVHD (cGVHD)–free relapse-free survival (CRFS) in 2,198 patients who underwent UCB (n = 838), haploidentical (n = 159), 7/8-BM (n = 241), or 7/8-PB (n = 960) HCT. All groups were divided by myeloablative conditioning (MAC) intensity or reduced intensity conditioning (RIC), except haploidentical group in which most received RIC. To account for multiple testing, P < .0071 in multivariable analysis and P < .00025 in direct pairwise comparisons were considered statistically significant. RESULTS In multivariable analysis, haploidentical group had the best GRFS, CRFS, and overall survival (OS). In the direct pairwise comparison of other groups, among those who received MAC, there was no difference in GRFS or CRFS among UCB, 7/8-BM, and 7/8-PB with serotherapy (alemtuzumab or antithymocyte globulin) groups. In contrast, the 7/8-PB without serotherapy group had significantly inferior GRFS, higher cGVHD, and a trend toward worse CRFS (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.69; P = .002) than the 7/8-BM group and higher cGVHD and trend toward inferior CRFS (HR, 1.36; 95% CI, 1.14 to 1.63; P = .0006) than the UCB group. Among patients with RIC, all groups had significantly inferior GRFS and CRFS compared with the haploidentical group. CONCLUSION Recognizing the limitations of a registry retrospective analysis and the possibility of center selection bias in choosing donors, our data support the use of UCB, 7/8-BM, or 7/8-PB (with serotherapy) grafts for patients undergoing MAC HCT and haploidentical grafts for patients undergoing RIC HCT. The haploidentical group had the best GRFS, CRFS, and OS of all groups.

Introduction: Paget’s disease affects 3–4% of the population; however, literature describing outcomes of total hip arthroplasty (THA) in this population are limited. Given the known concerns with bleeding, heterotopic ossification (HO), and component loosening, we describe our results with primary and revision THAs in Paget’s disease with emphasis on implant survivorship, radiographic results, and clinical outcomes. Methods: We identified 25 THAs performed with contemporary uncemented acetabular components in patients with Paget’s disease from 1999 to 2014. Mean age and follow-up were 78 and 7 years. Results: In primary THAs, survivorship free from aseptic acetabular and femoral loosening was 100% and 94% at 8 years. 7 patients (41%) received blood transfusions. HO was seen in 9 (53%). Mean Harris Hip Score (HHS) improved from 49 to 76. In revision THAs, survivorship free from acetabular and/or femoral aseptic loosening was 100% at 5 years. 3 patients (38%) received a transfusion. HO was seen in 5 (63%). Mean HHS improved from 52 to 77. There were no radiographic signs of aseptic loosening among unrevised cases in either group. Discussion: Our investigation demonstrates that concerns with acetabular fixation in Paget’s disease have been mitigated with contemporary uncemented acetabular components. Complications previously noted, namely intraoperative bleeding and HO, continue to be of concern.

Abstract PURPOSE: Recent advances in understanding of the molecular alterations that occur at the genetic and epigenetic levels in Multiple Myeloma (MM) have led to major leaps in identifying molecular pathways that regulate progression and resistance to therapeutic agents. However, despite great scientific advances at the genomic level, studies to identify signaling pathways deregulated at the functional proteomic level in MM are limited. In this study, we used a rapid and reproducible antibody-based protein microarray technique to screen the functional differences between malignant plasma cells in samples obtained from patients with MM compared to normal plasma cells (NPC) from the bone marrow of healthy volunteers. METHODS: We determined the protein expression level of 512 polypeptides in 12 samples of newly diagnosed patients with MM using high-throughput proteomic analysis with antibody-based protein microarray. Primary CD138+ sorted MM cells were obtained from the bone marrow of patients after informed consent. MM1.S was used in this study. Using immunohistochemistry and immunoblotting were confirmed. Lentivirus was used to knockdown CRIK. Gene expression datasets from the Mayo Clinic (accession number GSE 6477) and the UAMS (accession number GSE 2658) were obtained from the Gene Expression Omnibus for analysis. The Mayo dataset was generated using Affymetrix U133A platform whereas the UAMS dataset was generated using Affymetrix U133plus 2.0 platform. RESULTS: We identified four subgroups of MM using unsupervised clustering analysis. We confirmed overexpression of some of these proteins including CRIK and CDK4 using immunohistochemistry and immunoblotting. Many of these proteins are known to be deregulated in MM, indicating that this technique can accurately identify proteins that are over or under-expressed in MM in a high-throughput fashion. In addition, we identified novel proteins that are not previously known to be differentially expressed in MM, including the small GTPase member of the Rho family, CRIK protein. We then showed using knockdown of CRIK that this novel protein specifically regulates migration and adhesion in MM. There was no effect on survival of MM cells using the CRIK knockdown. Analyzing the GEP data of the 15 NPC, 46 monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM) and 101 MM samples from the Mayo Clinic, there was a significant increase in expression of CIT from NPC to MM. Among the 351 patients entered into TTII trials from UAMS, CIT expression was similar across the different TC class. Using a cut-off normalized expression level of 1.25 (a level above expression in NPC), MM with a high CIT expression (n=81) had a significantly shorter survival than the other patients. CONCLUSION: In this study, we show that MM cells express a high level of CRIK, and that inhibition of this protein leads to significant inhibition of adhesion and migration of MM cells. In addition, CRIK protein expression correlated with CIT gene expression, with high expression in MM samples compared to NPC. In addition, high CIT expression correlated with poor survival in patients with MM.