Total Femur Antibiotic Spacers: Effective Salvage for Complex Periprosthetic Joint Infections.

BACKGROUND: A simultaneous periprosthetic joint infection (PJI) of an ipsilateral hip and knee arthroplasty is a challenging complication of lower extremity reconstructive surgery. We evaluated the use of total femur antibiotic-impregnated polymethylmethacrylate (PMMA) bone cement spacers in the staged treatment of such limb-threatening PJIs. METHODS: Thirteen patients were treated with a total femur antibiotic spacer. The mean age at the time of spacer placement was 65 years. Nine patients had polymicrobial PJIs. All spacers incorporated vancomycin (3.0 g/40 g PMMA) and gentamicin (3.6 g/40 g PMMA), while 8 also included amphotericin (150 mg/40 g PMMA). Eleven spacers were biarticular. Twelve spacers were implanted through one longitudinal incision, while 8 of 12 reimplantations occurred through 2 smaller, separate hip and knee incisions. Mean follow-up after reimplantation was 3 years. RESULTS: Twelve (92%) patients underwent reimplantation of a total femur prosthesis at a mean of 26 weeks. One patient died of medical complications 41 days after spacer placement. At latest follow-up, 3 patients had experienced PJI recurrence managed with irrigation and debridement. One required acetabular component revision for instability. All 12 reimplanted patients retained the total femur prosthesis with no amputations. Eleven (91%) were ambulatory, and 7 (58%) remained on suppressive antibiotics. CONCLUSION: Total femur antibiotic spacers are a viable, but technically demanding, limb-salvage option for complex PJIs involving the ipsilateral hip and knee. In the largest series to date, there were no amputations and 75% of reimplanted patients remained infection-free. Radical debridement, antimicrobial diversity, prolonged spacer retention, and limiting recurrent soft tissue violation are potential tenets of success. LEVEL OF EVIDENCE: IV.

Comparison of Three Commercial Tools for Metagenomic Shotgun Sequencing Analysis.

Metagenomic shotgun sequencing for the identification of pathogens is being increasingly utilized as a diagnostic method. Interpretation of large and complicated data sets is a significant challenge, for which multiple commercial tools have been developed. Three commercial metagenomic shotgun sequencing tools, CosmosID, One Codex, and IDbyDNA, were compared to determine whether they result in similar interpretations of the same sequencing data. We selected 24 diverse samples from a previously characterized data set derived from DNA extracted from biofilms dislodged from the surfaces of resected arthroplasties (sonicate fluid). Sequencing data sets were analyzed using the three commercial tools and compared to culture results and prior metagenomic analysis interpretation. Identical interpretations from all three tools occurred for 6 samples. The total number of species identified included 28 by CosmosID, 59 by One Codex, and 41 by IDbyDNA. All of the tools performed similarly in detecting those microorganisms identified by culture, including polymicrobial mixes. These data show that while all of the tools performed well overall, there were some differences, particularly in their predilection for identifying low-abundance or contaminant organisms as present.

Aseptic Reoperations Within 1 Year of Primary Total Knee Arthroplasty Markedly Increase the Risk of Later Periprosthetic Joint Infection.

BACKGROUND: Despite the high rate of success of primary total knee arthroplasty (TKA), some patients are candidates for early aseptic reoperation. The goal of this study is to evaluate the risk of subsequent periprosthetic joint infection (PJI) in patients treated with an aseptic reoperation within 1 year of primary TKA. METHODS: A retrospective review of our total joint registry compared 249 primary TKAs requiring an aseptic reoperation within 1 year following index arthroplasty to a control group of 17,867 TKAs not requiring reoperation within 1 year. Patients were divided into groups based on time from index TKA: (1) 90 days or less (114 TKAs) and (2) 91 to 365 days (135 TKAs). Mean age was 68 years with 57% female. Mean follow-up was 7 years. RESULTS: At 2 years postoperatively, patients undergoing an aseptic reoperation within 90 days subsequently had a 9% PJI rate, while patients undergoing an aseptic reoperation between 91 and 365 days subsequently had a 3% PJI rate. The control group had a 0.4% PJI rate. Compared to the control group, patients undergoing an aseptic reoperation within 90 days had an elevated risk of PJI (hazard ratio, 9; P < .0001), as did patients who had a reoperation between 91 and 365 days (hazard ratio, 4; P < .0001). CONCLUSION: Aseptic reoperation within 1 year of primary TKA was associated with a notably increased risk of subsequent PJI.

The Lawrence D. Dorr Surgical Techniques & Technologies Award: Aseptic Reoperations Within One Year of Primary Total Hip Arthroplasty Markedly Increase the Risk of Later Periprosthetic Joint Infection.

BACKGROUND: Despite the success of primary total hip arthroplasties (THAs), some patients will require an aseptic reoperation within 1 year of the index THA. The goal of this study is to evaluate the risk of subsequent periprosthetic joint infection (PJI) in patients undergoing an aseptic reoperation within 1 year of a primary THA. METHODS: A retrospective review utilizing our institutional joint registry identified 211 primary THAs requiring aseptic reoperation within 1 year following index arthroplasty. A control group of 15,357 primary THAs not requiring reoperation within 1 year was identified. Patients were divided into groups based on time from primary THA to reoperation: (1) within 90 days (n = 112 THAs; 40% for dislocation, 34% for periprosthetic fracture) or (2) 91-365 days (n = 99 THAs; 37% for dislocation, 29% for periprosthetic fracture). Mean follow-up was 7 years. RESULTS: Patients undergoing an aseptic reoperation within 90 days had a PJI rate of 4.8% at 2 years, while the 91-365 day group had a PJI rate of 3.2% at 2 years. The control group had a PJI rate of 0.2% at 2 years. Employing a multivariate analysis, reoperation within 90 days of index arthroplasty had an elevated risk of PJI (hazard ratio 8, P < .001) as did a reoperation between 91 and 365 days (hazard ratio 13, P < .001). CONCLUSION: Aseptic reoperations within 1 year following primary THA resulted in an 8- to 13-fold increased risk of subsequent PJI. The risk was similar whether the aseptic reoperation was early (within 90 days) or later (91-365 days). LEVEL OF EVIDENCE: Level III (Prognostic).

Elevated Infection and Complication Rates in Patients Undergoing a Primary THA With a History of a PJI in a Prior Hip or Knee Arthroplasty: A Matched Cohort Study.

BACKGROUND: There are little data on the outcomes of primary total hip arthroplasties (THAs) in patients with a prior surgically treated hip or knee periprosthetic joint injection (PJI). The goal of this study was to compare the risk of infection in this population with matched controls. METHODS: We retrospectively reviewed 48 patients whom underwent 50 primary THAs from 2000 to 2014 with a history of a PJI in a total knee arthroplasty or contralateral THA. Thirteen patients (27%) were on chronic antibiotic suppression at the time of primary THA. Mean age was 67 years, and mean body mass index was 35 kg/m2. Mean follow-up was 6 years. We 1:3 matched (age, sex, body mass index, cemented vs cementless femoral fixation, and surgical year) these cases to 150 primary THAs. Competing risk analysis, with death as the competing risk, was performed. RESULTS: The cumulative incidence of PJI with death as a competing risk was 1.5-fold higher in the study cohort (2.0%) compared with matched controls (1.4%) (hazards ratio, 1.5; P = .75). The cumulative incidence of any infection with death as a competing risk was 2-fold higher in the study cohort (4.0%) compared with matched controls (2.1%) (hazards ratio, 2.0; P = .45). However, these were both statistically similar given the relatively small cohort. The overall complication rate, including infections and reoperations, was 17% in the study cohort. CONCLUSION: Patients undergoing a clean primary THA with a history of a total knee arthroplasty or contralateral THA PJI in another joint have a 2% and 4% risk of PJI and any infection, respectively. Moreover, nearly 1 in 5 patients experience at least 1 complication.

Infection After Unicompartmental Knee Arthroplasty: A High Risk of Subsequent Complications.

BACKGROUND: Unicompartmental knee arthroplasty restores function and improves pain in appropriately selected patients. Scant evidence exists regarding the treatment of periprosthetic joint infection (PJI) after unicompartmental knee arthroplasty (UKA). QUESTIONS/PURPOSES: (1) What was the overall survivorship free from reinfection? (2) What is the survivorship free of all-cause revision? (3) What are the Knee Society scores (KSS) and complications after surgical treatment of UKA PJI? METHODS: This retrospective study with data drawn from a longitudinally maintained institutional registry identified 15 UKA PJIs between 1992 and 2014. The median age at PJI diagnosis was 58 years (range, 41-82 years), nine of 15 were men, and the median body mass index was 29 kg/m (range, 23-36 kg/m). Ten patients (10 of 15) satisfied major Musculoskeletal Infection Society diagnostic criteria. There were five patients (five of 15) with early postoperative infections, five (five of 15) with acute hematogenous infections, and five (five of 15) with chronic PJIs. Two-stage exchange was performed in four patients with PJIs (four of 15), and débridement, antibiotics, and implant retention (DAIR) was performed in 11 patients (11 of 15) with PJIs. We performed Kaplan-Meier survivorship analysis for reinfection and revision procedures. Thirteen patients had a minimum of 2 years' followup and were included in the clinical analysis. Median followup was 4 years (range, 2-6 years). We calculated KSS. RESULTS: Infection-free survivorship was 71% at 5 years (95% confidence interval [CI], 46%-96%). Treatment success was higher for patients undergoing two-stage exchange (100% at 5 years; 95% CI, 100%-100%) versus DAIR (61% at 5 years; 95% CI, 31%-92%). Four of 11 patients undergoing DAIR had developed a reinfection at final followup. Survivorship free of any revision was 49% at 5 years (95% CI, 19%-79%). One patient from the two-stage exchange cohort underwent femoral component revision for aseptic loosening 5 years after PJI treatment, and two patients from the DAIR group were converted to TKA for disease progression at a mean of 4 years. In patients with a minimum of 2 years' followup, median KSS improved from 73 (range, 50-93) before index UKA to 94 (range, 55-100; p = 0.016). CONCLUSIONS: Treatment of UKA PJI with DAIR was associated with a lower infection-free survivorship at 5 years compared with two-stage exchange with conversion to TKA. Among those patients who were infection-free, a number needed reoperations for disease progression (in the DAIR group) or component loosening (in both groups). UKA PJI results in substantial morbidity, and patients with these infections should be followed closely for aseptic causes of failure in addition to infection recurrence. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Molecular pathology of total knee arthroplasty instability defined by RNA-seq.

Total knee arthroplasty (TKA) is a durable and reliable procedure to alleviate pain and improve joint function. However, failures related to flexion instability sometimes occur. The goal of this study was to define biological differences between tissues from patients with and without flexion instability of the knee after TKA. Human knee joint capsule tissues were collected at the time of primary or revision TKAs and analyzed by RT-qPCR and RNA-seq, revealing novel patterns of differential gene expression between the two groups. Interestingly, genes related to collagen production and extracellular matrix (ECM) degradation were higher in samples from patients with flexion instability. Partitioned clustering analyses further emphasized differential gene expression patterns between sample types that may help guide clinical interpretations of this complication. Future efforts to disentangle the effects of physical and biological (e.g., transcriptomic modifications) risk factors will aid in further characterizing and avoiding flexion instability after TKA.

Cost Analysis of Dual-Mobility Versus Large Femoral Head Constructs in Revision Total Hip Arthroplasty.

BACKGROUND: The purpose of this study is to report healthcare payer costs of dual-mobility (DM) and large femoral head (LFH) constructs in revision total hip arthroplasties (THAs). METHODS: A Markov model was constructed to analyze costs of re-interventions incurred by Medicare and private payers over a 3-year time horizon in patients who underwent unilateral revision THA with DM (n = 126) or LFH (n = 176) implants. Model states and probabilities were derived from prospectively collected registry data. Medicare costs were estimated as the weighted-average national Medicare payment for revision THA. Private payer costs were estimated by using a multiplier of Medicare costs. RESULTS: Over a 3-year period following revision THA, re-interventions were performed in 11 (9%) DM patients and 34 (19%) LFH patients, costing $263-$1898 in DM THAs and $1285-$3946 in LFH THAs for Medicare. When compared to LFH implants, DM constructs were less costly to Medicare and private payers, resulting in cost differentials of $1536 and $2611, respectively. CONCLUSIONS: At mid-term follow-up, DM constructs utilized in revision THAs were associated with 11% lower absolute risk of re-intervention and payer savings of $1500-$2500 per case when compared to LFH constructs. LEVEL OF EVIDENCE: Economic and decision analysis, Level III.

Mild Coronal Stem Malalignment Does Not Negatively Impact Survivorship or Clinical Results in Uncemented Primary Total Hip Arthroplasties With Dual-Tapered Implants.

BACKGROUND: Proper component positioning in total hip arthroplasty (THA) is crucial for implant fixation and hip stability. The purpose of this study is to assess if neutral coronal stem alignment (0° ± 3°) improved long-term survivorship in uncemented femoral components. METHODS: Between 2005 and 2010, 1028 primary THAs were performed with 2 contemporary dual-tapered, proximally coated uncemented stem types. Alignment was measured immediately postoperatively and at most recent follow-up. In total, 978 femoral stems (95%) were within 0° ± 3° of the neutral anatomic coronal axis, and the 50 stems (5%) outside that range were considered outliers (3.1° of valgus to 4.8° of varus). Outcomes analyzed included implant survivorship, Harris Hip Scores, and incidence of dislocation. Mean follow-up was 5 years. RESULTS: Survivorship free of aseptic femoral component loosening was 99.3% and 98.2% at 5 and 8 years in the neutral group vs 100% at 5 and 8 years in the outlier group (P = .98). Survivorship free of femoral component revision for any reason was 99.1% and 97.3% at 5 and 8 years vs 100% at 5 and 8 years, respectively (P = .80). Harris Hip Scores were similar (89 in both groups; P = .84) at most recent follow-up. The incidence of mild to moderate thigh pain was also similar in both groups (6.1% vs 6%, P = .85). The incidence of dislocation was 1.5% at 8 years, and similar between both groups (P = .77). CONCLUSION: Slight malalignment of contemporary dual-tapered uncemented THA femoral components does not appear to negatively impact survivorship or clinical outcomes, which is in contrast to cemented femoral components. LEVEL OF EVIDENCE III: Case-control study.

Identification of Prosthetic Joint Infection Pathogens Using a Shotgun Metagenomics Approach.

Background: Metagenomic shotgun sequencing has the potential to change how many infections, particularly those caused by difficult-to-culture organisms, are diagnosed. Metagenomics was used to investigate prosthetic joint infections (PJIs), where pathogen detection can be challenging. Methods: Four hundred eight sonicate fluid samples generated from resected hip and knee arthroplasties were tested, including 213 from subjects with infections and 195 from subjects without infection. Samples were enriched for microbial DNA using the MolYsis basic kit, whole-genome amplified, and sequenced using Illumina HiSeq 2500 instruments. A pipeline was designed to screen out human reads and analyze remaining sequences for microbial content using the Livermore Metagenomics Analysis Toolkit and MetaPhlAn2 tools. Results: When compared to sonicate fluid culture, metagenomics was able to identify known pathogens in 94.8% (109/115) of culture-positive PJIs, with additional potential pathogens detected in 9.6% (11/115). New potential pathogens were detected in 43.9% (43/98) of culture-negative PJIs, 21 of which had no other positive culture sources from which these microorganisms had been detected. Detection of microorganisms in samples from uninfected aseptic failure cases was conversely rare (7/195 [3.6%] cases). The presence of human and contaminant microbial DNA from reagents was a challenge, as previously reported. Conclusions: Metagenomic shotgun sequencing is a powerful tool to identify a wide range of PJI pathogens, including difficult-to-detect pathogens in culture-negative infections.

Direct Detection and Identification of Prosthetic Joint Infection Pathogens in Synovial Fluid by Metagenomic Shotgun Sequencing.

Metagenomic shotgun sequencing has the potential to transform how serious infections are diagnosed by offering universal, culture-free pathogen detection. This may be especially advantageous for microbial diagnosis of prosthetic joint infection (PJI) by synovial fluid analysis since synovial fluid cultures are not universally positive and since synovial fluid is easily obtained preoperatively. We applied a metagenomics-based approach to synovial fluid in an attempt to detect microorganisms in 168 failed total knee arthroplasties. Genus- and species-level analyses of metagenomic sequencing yielded the known pathogen in 74 (90%) and 68 (83%) of the 82 culture-positive PJIs analyzed, respectively, with testing of two (2%) and three (4%) samples, respectively, yielding additional pathogens not detected by culture. For the 25 culture-negative PJIs tested, genus- and species-level analyses yielded 19 (76%) and 21 (84%) samples with insignificant findings, respectively, and 6 (24%) and 4 (16%) with potential pathogens detected, respectively. Genus- and species-level analyses of the 60 culture-negative aseptic failure cases yielded 53 (88%) and 56 (93%) cases with insignificant findings and 7 (12%) and 4 (7%) with potential clinically significant organisms detected, respectively. There was one case of aseptic failure with synovial fluid culture growth; metagenomic analysis showed insignificant findings, suggesting possible synovial fluid culture contamination. Metagenomic shotgun sequencing can detect pathogens involved in PJI when applied to synovial fluid and may be particularly useful for culture-negative cases.

Otto Aufranc Award: Dual-mobility Constructs in Revision THA Reduced Dislocation, Rerevision, and Reoperation Compared With Large Femoral Heads.

BACKGROUND: Dislocation is one of the most common complications after revision THA. Dual-mobility constructs and large femoral heads (ie, 40 mm) are two contemporary, nonconstrained bearing options used in revision THA to minimize the risk of dislocation; however, it is not currently established if there is a clear benefit to using dual-mobility constructs over large femoral heads in the revision setting. QUESTIONS/PURPOSES: We sought to determine if dual-mobility constructs would provide a reduction in dislocation, rerevision for dislocation, and reoperation or other complications as compared with large femoral heads in revision THA. METHODS: From 2011 to 2014, a series of 355 THAs underwent revision for any reason and received either a dual-mobility construct (146 THAs) or a 40-mm large femoral head (209 THAs). Indications for either construct were based on surgeon judgment; however, there is a preference to use dual-mobility constructs in patients believed to be at higher risk of dislocation. In the dual-mobility group, 20 of 146 (14%) were excluded because of loss of followup before 2 years or because they had a dual-mobility shell cemented into a preexisting acetabular component. In the large head group, 33 of 209 (16%) were lost to followup before 2 years. Followup in the dual-mobility group was 3.3 ± 0.8 years and followup in the large head group was 3.9 ± 0.9 years. Primary endpoints included dislocation, rerevisions for dislocation, and reoperations, which were determined through our institution's total joint registry and verified by individual patient chart review. Age and body mass index were not different with the numbers available between the groups, but there was a slight predominance of females in the dual-mobility group (52% [66 of 126] female) versus the 40-mm large head group (41% [72 of 176] female) (p = 0.05). Notably, 33% (41 of 126) of patients receiving the dual-mobility constructs had the index revision THA done for a diagnosis of recurrent dislocation versus 9% (17 of 176) in the 40-mm large head group. Mean effective head size in the dual-mobility group was 47 mm (range, 38-58 mm). RESULTS: The subsequent frequency of dislocation in the dual-mobility construct group was less (3% [four of 126] dual-mobility versus 10% [17 of 176] in the 40-mm large head group; hazard ratio, 3.2 [1.1-9.4]; p = 0.03). Rerevision for dislocation in the dual-mobility construct group was less frequent (1% [one of 126] dual-mobility versus 6% [10 of 176] in the 40-mm large head group; hazard ratio, 7.1 [0.9-55.6]; p = 0.03). Reoperation for any cause in the dual-mobility construct group was less frequent (6% [eight of 126] dual-mobility versus 15% [27 of 176] in the 40-mm large head group; hazard ratio, 2.5 [1.1-5.5]; p = 0.02); there were no differences between the groups in terms of the overall percentage of complications in each group. CONCLUSIONS: When compared with patients treated with a 40-mm large femoral head, patients undergoing revision THA who received a dual-mobility construct had a lower risk of subsequent dislocation, rerevision for dislocation, and reoperation for any reason in the first several years postoperatively. Those findings were present despite selection bias in this study to use the dual-mobility construct in patients at the highest risk for subsequent dislocation. Given the lower risk of subsequent dislocation, rerevision, and reoperation with the dual-mobility construct, some surgeons may wish to consider whether the role of dual-mobility should be judiciously expanded in contemporary revision THA. LEVEL OF EVIDENCE: Level III, therapeutic study.

Two-Stage Revision Total Hip Arthroplasty With a Specific Articulating Antibiotic Spacer Design: Reliable Periprosthetic Joint Infection Eradication and Functional Improvement.

BACKGROUND: Two-stage revision utilizing spacers loaded with high-dose antibiotic cement prior to reimplantation remains the gold standard for treatment of periprosthetic joint infections (PJI) in total hip arthroplasty (THA) in North America, but there is a paucity of data on mid-term outcomes. We sought to analyze the survivorship free of infection, clinical outcomes, and complications of a specific articulating spacer utilized during 2-stage revision. METHODS: One hundred thirty-five hips (131 patients) undergoing a 2-stage revision THA for PJI with a specific articulating antibiotic spacer design from 2005 to 2013 were retrospectively reviewed. Infections were classified according to the Musculoskeletal Infection Society criteria. Mean age at resection was 65 years and mean follow-up was 5 years (rang, 2-10). RESULTS: Survivorship free of any infection after reimplantation was 92% and 88% at 2 and 5 years, respectively. Patients with a host-extremity grade of C3 compared to all patients with a host grade of A [hazard ratio (HR) 4.1, P = .05] were significant risk factors for poorer infection-free survivorship after reimplantation. Harris hip scores improved from a mean of 58 to a mean of 71 in the spacer phase (P = .002) and a mean of 81 post-reimplantation (P = .001). Fourteen (10%) patients dislocated after reimplantation, 9 (7%) of which required re-revision. Trochanteric deficiency (HR 19, P < .0001), dislocation of the articulating spacer prior to reimplantation [which occurred in 7 (5%) patients, 5 of whom subsequently dislocated the definitive implant] (HR 16, P < .0001), and female gender (HR 5, P = .002) were significant risk factors for post-reimplantation dislocation. CONCLUSION: Insertion of an articulating antibiotic spacer during a 2-stage revision THA for PJI demonstrates reliable infection eradication and improvement in clinical function, including the spacer phase. Patients with trochanteric deficiency and an articulating spacer dislocation are at high risk of post-reimplantation dislocation; judicial use of a dual-mobility or constrained device should be considered in these patients.

High Rate of Positive Cultures in Patients Referred With Antibiotic Spacers as Part of 2-Stage Exchange.

BACKGROUND: Two-stage exchange for periprosthetic joint infection (PJI) in total knee arthroplasty (TKA) remains the gold standard treatment in North America. Occasionally, patients with knee PJI are referred for definitive management after resection and antibiotic spacer placement. Currently, little literature exists to suggest how these patients should be managed. The purpose of this study is to report the clinical outcomes of these patients. METHODS: We retrospectively identified 54 patients (54 knees) from 2000 to 2012 treated for PJI with initial TKA resection and spacer placement performed somewhere other than the definitive treatment center. The mean age at reimplantation was 64 years, with 59% being male. Redebridement and antibiotic spacer exchange was performed for all patients. Mean follow-up was 6.5 years. RESULTS: Of the 54 knees, 22 (41%) grew an organism from a culture taken at the time of redebridement and spacer exchange. The most common organism identified at redebridement was Staphylococcus aureus (41%). Obtaining positive cultures at redebridement was not associated with presenting erythrocyte sedimentation rate (P = .46), C-reactive protein (P = .57), or the presence of retained cement (P = .13). Forty-nine of 54 (91%) knees were ultimately reimplanted. Two-year survivorship free of infection in reimplanted knees was 98%. CONCLUSION: Patients referred with an antibiotic knee spacer for PJI have a high rate of positive cultures at the time of redebridement. Neither the presenting serology nor the identification of retained cement was associated with obtaining positive cultures at the time of redebridement. Nevertheless, this unique cohort of patients has favorable outcomes when redebrided with spacer exchange prior to reimplantation.

Periprosthetic Joint Infection With Fungal Pathogens.

BACKGROUND: Although there is abundant information about bacterial periprosthetic joint infections (PJIs), there is a notable paucity of information about fungal PJIs. The goals of this study are to describe the patient demographics, diagnostic findings, and treatment results of fungal PJIs after total joint arthroplasty. METHODS: We identified 31 fungal PJIs (13 total hip arthroplasties and 18 total knee arthroplasties) in 31 patients treated between 1996 and 2014. This represented 0.9% of the 3525 PJIs treated at our institution during this time period. Candida species accounted for 81% of infections. The mean patient age at diagnosis of fungal PJI was 68 years. Mean follow-up after initiation of treatment was 4 years. RESULTS: In the total hip arthroplasty cohort, survivorship free from all-cause revision or implant removal was 44% at 2 years. Survivorship free from reinfection was 38% at 2 years. Mean Harris hip score was 27 at final follow-up.In the total knee arthroplasty cohort, survivorship free from all-cause revision was 70% at 2 years. Survivorship free from reinfection was 76% at 2 years. Mean Knee Society scores were 36 at final follow-up. CONCLUSION: Fungal PJIs are rare (0.9% of diagnosed PJIs). Survivorship free of all-cause revision or implant removal was very low in the hip group (44% at 2 years), but slightly better in the knee group (70% at 2 years). Moreover, clinical outcomes were poor with high perioperative complication rates. Improved treatment regimens are needed for this unsolved clinical problem.

Impact of Contaminating DNA in Whole-Genome Amplification Kits Used for Metagenomic Shotgun Sequencing for Infection Diagnosis.

Whole-genome amplification (WGA) is a useful tool for amplification of very small quantities of DNA for many uses, including metagenomic shotgun sequencing for infection diagnosis. Depending on the application, background DNA from WGA kits can be problematic. Three WGA kits were tested for their utility in a metagenomics approach to identify the pathogens in sonicate fluid comprised of biofilms and other materials dislodged from the surfaces of explanted prosthetic joints using sonication. The Illustra V2 Genomiphi, Illustra single cell Genomiphi, and Qiagen REPLI-g single cell kits were used to test identical sonicate fluid samples. Variations in the number of background reads, the genera identified in the background, and the number of reads from known pathogens known to be present in the samples were observed between kits. These results were then compared to those obtained with a library preparation without prior WGA using an NEBNext Ultra II paired-end kit, which requires a very small amount of input DNA. This approach also resulted in the presence of contaminant bacterial DNA and yielded fewer reads from the known pathogens. These findings highlight the impact that WGA kit selection can have on metagenomic analysis of low-biomass samples and the importance of the careful selection and consideration of the implications of using these tools.

What Risks are Associated with Primary THA in Recipients of Hematopoietic Stem Cell Transplantation?

INTRODUCTION: As patients who receive hematopoietic stem cell transplantation are at increased risk of avascular necrosis (AVN) and subsequent degenerative arthritis, THA may be considered in some of these patients, particularly as overall patient survival improves for patients undergoing stem-cell transplants. Patients receiving hematopoietic stem cell transplantation theoretically are at increased risk of experiencing complications, infection, and poorer implant survivorship owing to the high prevalence of comorbid conditions, immunosuppressive therapy regimens including corticosteroids, and often low circulating hematopoietic cell lines; however, there is a paucity of studies elucidating these risks. QUESTIONS/PURPOSES: We asked: (1) What is the overall mortality of patients with hematopoietic stem cell transplantation who have undergone THA? (2) What is the complication rate for these patients? (3) What are the revision and reoperation rates and implant survivorship for these patients? PATIENTS AND METHODS: Between 1999 and 2013, we performed 42 THAs in 36 patients who underwent stem-cell transplants. Other than those who died, all were available for followup at a minimum of 2 years; of the patients whose procedures were done more than 10 years ago and who are not known to have died, two (5%) had not been seen in the last 5 years and so are considered lost to followup. All patients underwent thorough evaluation by the transplant team before arthroplasty; general contraindications included active medical comorbidities or evidence of unstable end-organ damage, active rejection, and critically low circulating hematopoietic cell lines. Underlying primary diseases leading to hematopoietic stem cell transplantation included lymphoma (14/42; 33%), plasma cell disorders (10/42; 24%), leukemia (9/42; 21%), and amyloidosis (3/42; 7%). Complications, reoperations, revisions, and implant and patient survivorship, were recorded from chart review and data from the institutional total joint registry. Mean followup was 5 years (range, 2-15 years). RESULTS: Patient survivorship free of mortality was 91% (95% CI, 81%-100%) and 82% (95% CI, 68%-96%) at 2 and 5 years, respectively. Complications occurred in four of 42 THAs (10%); these complications included an intraoperative fracture and a venous thromboembolism. Revisions occurred in two of 42 (5%) THAs; there were no reoperations. Implant survivorship free of component revision for any reason or implant removal accounting for death as a competing risk was 93% (95% CI, 83%-100%) at 5 years. CONCLUSION: With appropriate medical evaluation and comanagement by transplant specialists, carefully selected patients with hematopoietic stem cell transplants may undergo elective primary THA, although complications do occur in this relatively fragile patient population. Although implant survivorship was modest at 93% at 5 years, there was not a high risk of revision for infection. Improved outcomes for these patients may be expected as their medical management advances and additional comparative studies may clarify other important patient factors. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Antibacterial and Biocompatible Titanium-Copper Oxide Coating May Be a Potential Strategy to Reduce Periprosthetic Infection: An In Vitro Study.

BACKGROUND: Periprosthetic infections are devastating for patients and more efficacious preventive strategies are needed. Surface-modified implants using antibacterial coatings represent an option to cope with this problem; however, manufacturing limitations and cytotoxicity have curbed clinical translation. Among metals with antibacterial properties, copper has shown superior in vitro antibacterial performance while maintaining an acceptable cytotoxicity profile. A thin film containing copper could prevent early biofilm formation to limit periprosthetic infections. This pilot study presents the in vitro antibacterial effect, cytotoxicity, and copper ion elution pattern of a thin film of titanium-copper oxide (TiCuO). QUESTIONS/PURPOSES: (1) Do titanium alloy (Ti6Al4V) discs coated with a thin film of TiCuO reduce Staphylococcus epidermidis biofilm and planktonic cell density compared with uncoated discs? (2) Do Ti6Al4V discs coated with a thin film of TiCuO affect normal human osteoblast viability compared with untreated cells? (3) Is copper ion concentration generated by coated discs lower than previously published copper ion concentrations that cause 50% toxicity in similar human cell lines in vitro (TC50)? METHODS: Ninety Ti6Al4V discs (12.5 mm diameter; 1.25 mm thick) were used in this study. Seventy-two Ti6Al4V discs were coated with a thin film of either titanium oxide (TiO) or TiCuO containing 20%, 40%, or 80% copper using high-power impulse magnetron sputtering (HiPIMS). Eighteen Ti6Al4V discs remained uncoated for control purposes. We tested antibacterial properties of S epidermidis grown on discs in wells containing growth medium. After 24 hours, planktonic bacteria as well as biofilms removed by sonication were quantitatively cultured. Annexin/Pi staining was used to quantify in vitro normal human osteoblast cell viability at 24 hours and Day 7, respectively. Copper elution was measured at Days 1, 2, 3, 7, 14, and 28 using an inductively coupled plasma mass spectrometer to analyze aliquots of culture medium. Copper ion concentration achieved at 24 hours was compared with previously published TC50 for gingival fibroblast, a phenotypically similar cell line with available data regarding copper ion exposure. RESULTS: Discs coated with TiCuO 80% copper showed greater biofilm and planktonic cell density reduction when compared with other tested compositions (analysis of variance [ANOVA]; p < 0.001). Discs coated with TiCuO 80% copper showed mean biofilm and planktonic cell density of 4.0 log10 (SD = 0.4) and 5.7 log10 (SD = 0.2). Discs coated with TiCuO 80% showed a mean difference in biofilm and planktonic cell density of 2.5 log10 (95% confidence interval [CI], 1.9-3.1 log10; p < 0.001) and 1.2 (95% CI, 0.6-1.8; p < 0.001), respectively, when compared with uncoated discs. Normal human osteoblast viability did not differ among all groups at 24 hours (ANOVA; p = 0.2) and Day 7 (ANOVA; p = 0.7). Discs coated with TiCuO 80% copper showed a mean difference (95% CI) in relative cell viability (%) at 24 hours and Day 7 of 31.1 (95% CI, -19.4 to 81.7; p = 0.4) and -5.0 (95% CI, -7.8 to 17.9; p = 0.9), respectively, when compared with untreated cells. For all TiCuO-coated discs, copper ion elution peaked at 24 hours and slowly decreased in a curvilinear fashion to nearly undetectable levels by Day 28. Discs coated with TiCuO 80% copper showed mean copper ion concentration at 24 hours of 269.4 µmol/L (SD = 25.2 µmol/L) and this concentration was lower than previously published TC50 for similar human cell lines at 24 hours (344 µmol/L, SEM = 44 µmol/L). CONCLUSIONS: This pilot study demonstrates a proof of concept that a thin-film implant coating with TiCuO can provide a potent local antibacterial environment while remaining relatively nontoxic to a human osteoblast cell line. Further research in an animal model will be necessary to establish efficacy and safety of this technique and whether it might be useful in the design of implants. CLINICAL RELEVANCE: A thin film coating with TiCuO demonstrates high antibacterial activity and low cellular cytotoxicity to human osteoblasts in vitro. Taken together, these properties represent a potential strategy for preventing periprosthetic infection if further work in animal models can confirm these results in vivo.

Conversion of Hip Hemiarthroplasty to Total Hip Arthroplasty Utilizing a Dual-Mobility Construct Compared With Large Femoral Heads.

BACKGROUND: Conversion of hemiarthroplasty to total hip arthroplasty (THA) has a historically high, up to 20%, postoperative dislocation rate. As such, dual-mobility (DM) constructs are an attractive option to mitigate this complication. We analyzed survivorship free of revision, complications, and clinical outcomes of hemiarthroplasties conversion to THAs utilizing DM constructs compared with large femoral heads (≥36 mm). METHODS: Conversion of 16 hemiarthroplasties to THAs with a specific DM construct compared with 13 conversions utilizing large femoral heads (≥36 mm) from 2011 to 2014 were reviewed. Mean age at conversion in the DM group was 75 years (range, 57-93 years); 75% were female. Significantly more patients with a dislocated hemiarthroplasty were converted to DM constructs compared to large femoral heads (44% vs 0%; P = .01). Mean follow-up was 3 years. RESULTS: Survivorship free of revision was 100% in the DM group compared with 92% in the large femoral head cohort at 2 years (P = .7). One (8%) patient converted to a large femoral head underwent revision to a constrained liner for recurrent dislocations while no patients experienced a postoperative dislocation in the DM group (P = .4). Harris Hip Scores improved from 54 to 82 (P < .01) in the DM group, and from 52 to 86 in the large femoral head group (P < .01). CONCLUSION: Larger effective femoral heads used during conversion of hemiarthroplasties to THAs resulted in high survivorship free of revision, minimal complications, and excellent clinical outcomes at short-term follow-up. In patients at highest risk for postoperative dislocation, including those with dislocating hemiarthroplasties, DM constructs resulted in no postoperative dislocations.

Retained Antibiotic Spacers After Total Hip and Knee Arthroplasty Resections: High Complication Rates.

BACKGROUND: Prolonged retention of an antibiotic spacer is occasionally chosen during treatment of periprosthetic joint infections after total hip arthroplasty (THA) and total knee arthroplasty (TKA). The purpose of our study was to evaluate the outcome of extended spacer retention. METHODS: We reviewed 1106 cases of periprosthetic joint infection after THA (n = 308) and TKA (n = 798) and identified 17 (5.5%) retained hip and 34 (4.3%) retained knee spacers. Most patients (35 of 51, 69%) underwent spacer retention because they were medically unfit for further surgery. The remaining patients (16 of 51, 31%) had acceptable function and forewent further surgery. Competing risk analyses, with death as the competing risk, determined the cumulative incidence of reinfection and spacer revision. Radiographic analysis and clinical outcomes were analyzed. RESULTS: The 2-year cumulative incidence for reinfection was 7% for retained hip and 13% for retained knee spacers. The cumulative incidence for all-cause spacer revision was 28% at 4 years for hips and 21% at 2 years for knees. The most common complications were implant migration and femoral spacer subsidence in the hip cohort, and supracondylar femur fractures and spacer dislocations in the knee cohort. The cumulative incidence for radiographic signs of mechanical failure was 72% and 87% at late follow-up for the hip and knee groups, respectively. The latest Harris Hip Score and Knee Society Score were 62 and 63, respectively. CONCLUSION: Antibiotic spacer retention is a rare event in the course of planned 2-stage treatment of infected THA or TKA. Failure secondary to recurrent infection is uncommon; however, failure for mechanical reasons is frequent and clinical outcomes are relatively poor.