Diaphyseal Impaction Grafting Combined with Metaphyseal Cones: Outcomes in 88 Revision Total Knee Arthroplasties.

BACKGROUND: Metaphyseal cones with cemented stems can be successfully utilized in most revision total knee arthroplasties (TKAs). However, if the diaphysis has been previously violated, fixation of the cemented stem, which is important for cone ingrowth and construct survival, can be compromised. The initial results of our novel technique combining diaphyseal impaction bone-grafting with a metaphyseal cone were promising but required additional study. The purpose of the present study was to assess results of this technique in a larger cohort. METHODS: A metaphyseal cone combined with diaphyseal impaction grafting and a cemented stem was utilized in 88 revision TKAs at our institution, including 35 from our prior study. The mean age at the time of revision was 67 years, and 67% of patients were male. Patients had had a mean of 4 prior knee arthroplasty procedures. The 2 most common reasons for revision were aseptic loosening (78%) and 2-stage reimplantation for periprosthetic joint infection (PJI) (19%). The mean follow-up was 4 years. RESULTS: At the time of the latest follow-up, no cone-impaction grafting constructs required re-revision for aseptic loosening. Five-year survivorship free from any revision of the cone-impaction grafting construct and free from any reoperation was 95% and 65%, respectively. A total of 25 knees (28%) underwent reoperation, with the 2 most common indications being PJI and periprosthetic fracture. All cones were osseointegrated, and all bone graft appeared stable or incorporated. One patient had radiographic evidence of tibial component loosening despite a well-fixed cone; however, this patient was asymptomatic and had not undergone revision at 9 years. CONCLUSIONS: When presented with a sclerotic, polished diaphyseal canal with deficient cancellous bone and concomitant metaphyseal bone loss, our technique of combining diaphyseal impaction grafting with a metaphyseal cone proved extremely durable in this larger series of patients. No cone-impaction grafting constructs required re-revision for aseptic loosening. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Efficacy of ADIPOR1 and ADIPOR2 peptide-agonist AdipoRon in preventing contracture in a rabbit model of arthrofibrosis.

AdipoRon is an adiponectin receptor 1, 2 (ADIPOR1 and ADIPOR2) agonist with potential antifibrotic effects. Whether AdipoRon can mitigate joint stiffness in a rabbit model of arthrofibrosis is unknown. We examined the efficacy of intravenous (IV) AdipoRon at mitigating contracture in a rabbit model of knee arthrofibrosis. Fifty-six female New Zealand White rabbits were divided into three dosing groups: vehicle (dimethyl sulfoxide, DMSO), 2.5 mg/kg AdipoRon, and 5 mg/kg AdipoRon. AdipoRon, in DMSO, was administered IV preoperatively and for 5 days postoperatively (30 rabbits, Aim 1). AdipoRon was again dosed similarly after Kirschner wire (K-wire) removal at 8 weeks (26 rabbits; Aim 2). The primary outcome of joint passive extension angle (PEA,°) was measured at 8, 10, 12, 16, and 24 weeks following index surgery. At 24 weeks, rabbits were euthanized and limbs were harvested to measure posterior capsular stiffness (N cm/°). In Aim 1, the 5 mg/kg treated rabbits had a significant increase in PEA when compared to controls at 16-week (p < 0.05). In Aim 2, the 5 mg/kg treated rabbits had a significant increase in PEA when compared to controls at 10-week (p < 0.05). In both aims, no significant differences were observed at later time points. Capsular stiffness was no different in any group. We are the first to report the efficacy of IV AdipoRon in a rabbit model of arthrofibrosis. We identified a significant dose-dependent decrease in joint PEA at early time points; however, no differences were observed between groups at later time points. Clinical Significance: The present investigation provided the first assessment of AdipoRon's efficacy in mitigating knee stiffness in the current gold standard rabbit model of arthrofibrosis. Results of this investigation provided further evidence as to the potential role of AdipoRon as a preventative for arthrofibrosis in large mammals.

Two Iron(II), α-Ketoglutarate-Dependent Enzymes Encoded by the PPZ Gene Cluster of Metarhizium majus Enable Production of 8-Hydroxyperamine.

Entomopathogenic fungus Metarhizium majus contains the nine-gene PPZ cluster, with ppzA, encoding a peramine-producing nonribosomal peptide synthetase, as the central component. In this work, the roles of two α-ketoglutarate, iron-dependent oxygenases encoded by the PPZ genes ppzC and ppzD were elucidated. PpzD was found to produce both trans-4-hydroxy-l-proline and trans-3-hydroxy-l-proline in a 13.1:1 ratio, yielding a key precursor for peramine biosynthesis. PpzC was found to act directly on peramine, yielding the novel analogue 8-hydroxyperamine.

Green Space and Internalizing or Externalizing Symptoms Among Children.

Importance: Evidence suggests that living near green space supports mental health, but studies examining the association of green space with early mental health symptoms among children are rare. Objective: To evaluate the association between residential green space and early internalizing (eg, anxiety and depression) and externalizing (eg, aggression and rule-breaking) symptoms. Design, Setting, and Participants: Data for this cohort study were drawn from the Environmental Influences on Child Health Outcomes cohort; analysis was conducted from July to October 2023. Children born between 2007 and 2013 with outcome data in early (aged 2-5 years) and/or middle (aged 6-11 years) childhood who resided in 41 states across the US, drawing from clinic, hospital, and community-based cohorts, were included. Cohort sites were eligible if they recruited general population participants and if at least 30 children had outcome and residential address data to measure green space exposure. Nine cohorts with 13 sites met these criteria. Children diagnosed with autism or developmental delay were excluded, and 1 child per family was included. Exposures: Green space exposure was measured using a biannual (ie, summer and winter) Normalized Difference Vegetation Index, a satellite image-based indicator of vegetation density assigned to monthly residential history from birth to outcome assessment. Main Outcome and Measures: Child internalizing and externalizing symptoms were assessed using the Child Behavior Checklist for Ages 1½ to 5 or 6 to 18. The association between green space and internalizing and externalizing symptoms was modeled with multivariable linear regression using generalized estimating equations, adjusting for birthing parent educational level, age at delivery, child sex, prematurity, and neighborhood socioeconomic vulnerability. Models were estimated separately for early and middle childhood samples. Results: Among 2103 children included, 1061 (50.5%) were male; 606 (29.1%) identified as Black, 1094 (52.5%) as White, 248 (11.9%) as multiple races, and 137 (6.6%) as other races. Outcomes were assessed at mean (SD) ages of 4.2 (0.6) years in 1469 children aged 2 to 5 years and 7.8 (1.6) years in 1173 children aged 6 to 11 years. Greater green space exposure was associated with fewer early childhood internalizing symptoms in fully adjusted models (b = -1.29; 95% CI, -1.62 to -0.97). No associations were observed between residential green space and internalizing or externalizing symptoms in middle childhood. Conclusions and Relevance: In this study of residential green space and children's mental health, the association of green space with fewer internalizing symptoms was observed only in early childhood, suggesting a sensitive period for nature exposure. Policies protecting and promoting access to green space may help alleviate early mental health risk.

Smooth muscle cell-derived Cxcl12 directs macrophage accrual and sympathetic innervation to control thermogenic adipose tissue.

Sympathetic innervation of brown adipose tissue (BAT) controls mammalian adaptative thermogenesis. However, the cellular and molecular underpinnings contributing to BAT innervation remain poorly defined. Here, we show that smooth muscle cells (SMCs) support BAT growth, lipid utilization, and thermogenic plasticity. Moreover, we find that BAT SMCs express and control the bioavailability of Cxcl12. SMC deletion of Cxcl12 fosters brown adipocyte lipid accumulation, reduces energy expenditure, and increases susceptibility to diet-induced metabolic dysfunction. Mechanistically, we find that Cxcl12 stimulates CD301+ macrophage recruitment and supports sympathetic neuronal maintenance. Administering recombinant Cxcl12 to obese mice or leptin-deficient (Ob/Ob) mice is sufficient to boost macrophage presence and drive sympathetic innervation to restore BAT morphology and thermogenic responses. Altogether, our data reveal an SMC chemokine-dependent pathway linking immunological infiltration and sympathetic innervation as a rheostat for BAT maintenance and thermogenesis.

Porous Tantalum Tibial Metaphyseal Cones in Revision TKA: Excellent 10-Year Survivorship.

BACKGROUND: Highly porous metal tibial metaphyseal cones (TMCs) are commonly utilized in revision total knee arthroplasty (TKA) to address bone loss and obtain biologic fixation. Mid-term (5 to 10 year) studies have previously demonstrated excellent survivorship and high rates of osseointegration, but longer-term studies are lacking. We aimed to assess long-term (≥ 10 year) implant survivorship, complications, and clinical and radiographic outcomes after revision TKA with TMCs. METHODS: Between 2004 and 2011, 228 revision TKAs utilizing porous tantalum TMCs with stemmed tibial components were performed at a single institution and were retrospectively reviewed. The mean age at revision was 65 years, the mean BMI was 33, and 52% were women. Implant survivorship, complications, and clinical and radiographic outcomes were assessed. The mean follow-up was 6.3 years. RESULTS: The 10-year survivorship free of aseptic loosening leading to TMC removal was 97%, free of any TMC removal was 88%, free of any re-revision was 66%, and free of any reoperation was 58%. The most common indications for re-revision were periprosthetic joint infection (PJI), instability, and aseptic femoral component loosening. The 10-year non-operative complication rate was 24%. The mean Knee Society scores increased from 38 preoperatively to 69 at 10 years. There were eight knees that had evidence of partial, progressive tibial radiolucencies at 10 years. CONCLUSIONS: Porous tantalum TMCs demonstrated persistently durable longer-term survivorship with a low rate of implant removal. The rare implant removals for component loosening or instability were offset by those required for PJI, which accounted for 80% of cone removals. Porous tantalum TMCs provide an extremely reliable tool to address tibial bone loss and achieve durable long-term fixation in revision TKA.

Modular fluted tapered stems in two-stage reimplantation of previously infected total hip arthroplasties.

Aims: Uncemented implants are now commonly used at reimplantation of a two-stage revision total hip arthoplasty (THA) following periprosthetic joint infection (PJI). However, there is a paucity of data on the performance of the most commonly used uncemented femoral implants - modular fluted tapered (MFT) femoral components - in this setting. This study evaluated implant survival, radiological results, and clinical outcomes in a large cohort of reimplantation THAs using MFT components. Methods: We identified 236 reimplantation THAs from a single tertiary care academic institution from September 2000 to September 2020. Two designs of MFT femoral components were used as part of an established two-stage exchange protocol for the treatment of PJI. Mean age at reimplantation was 65 years (SD 11), mean BMI was 32 kg/m2 (SD 7), and 46% (n = 109) were female. Mean follow-up was seven years (SD 4). A competing risk model accounting for death was used. Results: The 15-year cumulative incidence of any revision was 24%. There were 48 revisions, with the most common reasons being dislocation (n = 25) and infection (n = 16). The 15-year cumulative incidence of any reoperation was 28%. Only 13 revisions involved the fluted tapered component (FTC), for a 15-year cumulative incidence of any FTC revision of 8%. Only two FTCs were revised for aseptic loosening, resulting in a 15-year cumulative incidence of FTC revision for aseptic loosening of 1%. Stem subsidence ≥ 5 mm occurred in 2% of unrevised cases. All stems were radiologically stable at most recent follow-up. Mean Harris Hip Score was 69 (SD 20) at most recent follow-up. Conclusion: This series demonstrated that MFT components were durable and reliable in the setting of two-stage reimplantation THA for infection. While the incidence of aseptic loosening was very low, the incidence of any revision was 24% at 15 years, primarily due to dislocation and recurrent PJI.

Is the Rise of Medicare Advantage Impacting the Fidelity of Traditional Medicare Claims Data? Implications for Reporting of Long-Term Total Hip Arthroplasty Survivorship.

BACKGROUND: Arthroplasty registries often use traditional Medicare (TM) claims data to report long-term total hip arthroplasty (THA) survivorship. The purpose of this study was to determine whether the large number of patients leaving TM for Medicare Advantage (MA) has compromised the fidelity of TM data. METHODS: We identified 10,962 THAs in 9,333 Medicare-eligible patients who underwent primary THA from 2000 to 2020 at a single institution. Insurance type was analyzed, and 83% of patients had TM at the time of THA. Survivorship free from any revision or reoperation was calculated for patients who have TM. The same survivorship end points were recalculated with censoring performed when a patient transitioned to an MA plan after their primary THA to model the impact of losing patients from the TM dataset. Differences in survivorship were compared. The mean follow-up was 7 years. RESULTS: From 2000 to 2020, there was a decrease in TM insurance (93 to 73%) and a corresponding increase in MA insurance (0 to 19%) among THA patients. Following THA, 23% of TM patients switched to MA. For patients who had TM at the time of surgery, 15-year survivorship free from any reoperation or revision was 90% and 93%, respectively. When censoring patients upon transition from TM to MA, survivorship free from any reoperation became significantly higher (92 versus 90% at 15 years; hazard ratio = 1.16, P = .033), and there was a trend toward higher survivorship free from any revision (95 versus 93% at 15 years; hazard ratio = 1.16, P = .074). CONCLUSIONS: Approximately 1 in 4 patients left TM for MA after primary THA, effectively making them lost to follow-up within TM datasets. The mass exodus of patients out of TM appears to have led to a slight overestimation of survivorship free from any reoperation and trended toward overestimating survivorship free from any revision. If MA continues to grow, efforts to obtain MA data will become even more important.

Cemented dual-mobility constructs in uncemented revision acetabular components.

Aims: Dislocation remains a leading cause of failure following revision total hip arthroplasty (THA). While dual-mobility (DM) bearings have been shown to mitigate this risk, options are limited when retaining or implanting an uncemented shell without modular DM options. In these circumstances, a monoblock DM cup, designed for cementing, can be cemented into an uncemented acetabular shell. The goal of this study was to describe the implant survival, complications, and radiological outcomes of this construct. Methods: We identified 64 patients (65 hips) who had a single-design cemented DM cup cemented into an uncemented acetabular shell during revision THA between 2018 and 2020 at our institution. Cups were cemented into either uncemented cups designed for liner cementing (n = 48; 74%) or retained (n = 17; 26%) acetabular components. Median outer head diameter was 42 mm. Mean age was 69 years (SD 11), mean BMI was 32 kg/m2 (SD 8), and 52% (n = 34) were female. Survival was assessed using Kaplan-Meier methods. Mean follow-up was two years (SD 0.97). Results: There were nine cemented DM cup revisions: three for periprosthetic joint infection, three for acetabular aseptic loosening from bone, two for dislocation, and one for a broken cup-cage construct. The two-year survivals free of aseptic DM revision and dislocation were both 92%. There were five postoperative dislocations, all in patients with prior dislocation or abductor deficiency. On radiological review, the DM cup remained well-fixed at the cemented interface in all but one case. Conclusion: While dislocation was not eliminated in this series of complex revision THAs, this technique allowed for maximization of femoral head diameter and optimization of effective acetabular component position during cementing. Of note, there was only one failure at the cemented interface.

Do breast cancer patients have increased risk of complications after primary total hip and total knee arthroplasty?

Aims: Breast cancer survivors have known risk factors that might influence the results of total hip arthroplasty (THA) or total knee arthroplasty (TKA). This study evaluated clinical outcomes of patients with breast cancer history after primary THA and TKA. Methods: Our total joint registry identified patients with breast cancer history undergoing primary THA (n = 423) and TKA (n = 540). Patients were matched 1:1 based upon age, sex, BMI, procedure (hip or knee), and surgical year to non-breast cancer controls. Mortality, implant survival, and complications were assessed via Kaplan-Meier methods. Clinical outcomes were evaluated via Harris Hip Scores (HHSs) or Knee Society Scores (KSSs). Mean follow-up was six years (2 to 15). Results: Breast cancer patient survival at five years was 92% (95% confidence interval (CI) 89% to 95%) after THA and 94% (95% CI 92% to 97%) after TKA. Breast and non-breast cancer patients had similar five-year implant survival free of any reoperation or revision after THA (p ≥ 0.412) and TKA (p ≥ 0.271). Breast cancer patients demonstrated significantly lower survival free of any complications after THA (91% vs 96%, respectively; hazard ratio = 2 (95% CI 1.1 to 3.4); p = 0.017). Specifically, the rate of intraoperative fracture was 2.4% vs 1.4%, and venous thromboembolism (VTE) was 1.4% and 0.5% for breast cancer and controls, respectively, after THA. No significant difference was noted in any complications after TKA (p ≥ 0.323). Both breast and non-breast cancer patients experienced similar improvements in HHSs (p = 0.514) and KSSs (p = 0.132). Conclusion: Breast cancer survivors did not have a significantly increased risk of mortality or reoperation after primary THA and TKA. However, there was a two-fold increased risk of complications after THA, including intraoperative fracture and VTE.

Obesity and Primary Total Hip Arthroplasty: The Absolute versus Relative Risk of Periprosthetic Joint Infection at 15 Years.

BACKGROUND: To make an informed decision about total hip arthroplasty (THA), surgeons and patients need to understand the absolute and relative risks of periprosthetic joint infection (PJI). We sought to evaluate the long-term risk of PJI following primary THA stratified by body mass index (BMI) and PJI-related risk factors. METHODS: We identified 21,550 primary THAs performed from 2000 to 2021 at a single institution. Patients were stratified as having 0, 1, or ≥ 2 PJI risk factors (diabetes, chronic kidney disease, nonprimary osteoarthritis, immunosuppression, or active smoking) and into BMI categories. The 15-year cumulative risk of PJI was evaluated by BMI and PJI risk factors. RESULTS: For the entire cohort, the 15-year absolute risk of PJI was 2%. For patients who did not have PJI risk factors, the absolute risk of PJI at 15 years was 1% in normal weight, 2% in class III obesity, and 4% in class IV obesity. Patients who had class III and IV obesity had a 3-times and 9-times higher relative risk of PJI, respectively (P = .03, P < .001). Among patients who had ≥ 2 PJI risk factors, the absolute risk of PJI at 15 years was 2% in normal weight, 4% in class III obesity, and 18% in class IV obesity. CONCLUSIONS: Healthy patients who had class III and IV obesity had a 3-times and 9-times increased risk of PJI at 15 years relative to normal weight patients. However, the absolute risk of PJI at 15 years was 2 and 4%, respectively. Given emerging data questioning whether BMI modification decreases PJI risk, surgeons and patients must consider both a 3-times to 9-times increased relative risk of PJI and a 2 to 4% absolute risk of PJI at 15 years for healthy patients who had a BMI ≥ 40. LEVEL OF EVIDENCE: IV.

Periprosthetic Hip and Knee Infection: Is an Ipsilateral Uninfected Total Joint Arthroplasty at Risk?

BACKGROUND: Periprosthetic joint infections (PJIs) of total hip arthroplasty (THA) or total knee arthroplasty (TKA) may occur in the setting of an uninfected ipsilateral prosthetic joint. However, the risk to that uninfected ipsilateral joint is unknown. We analyzed the survivorship free from PJI in at risk THAs and TKAs following treatment of an ipsilateral knee or hip PJI, respectively. METHODS: Using our institutional total joint registry, we identified 205 patients who underwent treatment for PJI (123 THAs and 83 TKAs) with an at-risk ipsilateral in situ knee or hip, respectively, between 2000 and 2019. In total, 54% of index PJIs were chronic and 46% were acute. The mean age was 70 years, 47% were female, and the mean body mass index was 32. Kaplan-Meier survivorship analyses were performed. Mean follow-up was 6 years. RESULTS: The 5-year survivorship free of PJI in an at-risk THA after an ipsilateral TKA was treated for PJI was 97%. The 5-year survivorship free of PJI in an at-risk TKA when the ipsilateral THA was treated for PJI was 99%. Three PJIs occurred (2 THAs and 1 TKA), all over 1 year from the index ipsilateral PJI treatment. One hip PJI was an acute hematogenous infection that resulted from pneumonia. The other 2 new PJIs were caused by the same organism as the index PJI and were due to a failure of source control at the index joint. CONCLUSIONS: When diagnosed with PJI in a single joint, the risk of developing PJI in an ipsilateral prosthetic joint within 5 years was low (1 to 3% risk). In the rare event of an ipsilateral infection, all occurred greater than one year from the index PJI and 2 of 3 were with the same organism when source infection control failed. LEVEL OF EVIDENCE: Prognostic Level III.

BioCloneBot: A versatile, low-cost, and open-source automated liquid handler.

Liquid handler systems can provide significant benefits to researchers by automating laboratory work, however, their unaffordable price provides a steep barrier to entry. Therefore, we provide the BioCloneBot, a versatile, low-cost, and open-source automated liquid handler. This system can be easily built with 3D-printed parts and readily available commercial components. The BioCloneBot is highly adaptive to user needs and facilitates various liquid handling tasks in research and diagnostics. Its user-friendly interface and programmable nature make it suitable for a wide range of applications, from small-scale experiments to larger laboratory setups. By utilizing BioCloneBot, researchers and scientists can streamline their liquid handling processes without the financial constraints posed by traditional systems. In this paper, we detail the design, construction, and validation of BioCloneBot, showcasing its precise control, accuracy, and repeatability in various liquid handling tasks. The open-source nature of the system encourages collaboration and customization, enabling researchers to contribute and adapt the technology to specific experimental requirements.

Solvent Suppression in Pure Shift NMR.

Intense solvent signals in 1H solution-state NMR experiments typically cause severe distortion of spectra and mask nearby solute signals. It is often infeasible or undesirable to replace a solvent with its perdeuterated form, for example, when analyzing formulations in situ, when exchangeable protons are present, or for practical reasons. Solvent signal suppression techniques are therefore required. WATERGATE methods are well-known to provide good solvent suppression while enabling retention of signals undergoing chemical exchange with the solvent signal. Spectra of mixtures, such as pharmaceutical formulations, are often complicated by signal overlap, high dynamic range, the narrow spectral width of 1H NMR, and signal multiplicity. Here, we show that by combining WATERGATE solvent suppression with pure shift NMR, ultrahigh-resolution 1H NMR spectra can be acquired while suppressing intense solvent signals and retaining exchangeable 1H signals. The new method is demonstrated in the analysis of cyanocobalamin, a vitamin B12 supplement, and of an eye-drop formulation of atropine.

The Chitranjan S. Ranawat Award: Manipulation Under Anesthesia to Treat Postoperative Stiffness After Total Knee Arthroplasty: A Multicenter Randomized Clinical Trial.

BACKGROUND: Manipulation under anesthesia (MUA) occurs in 4% of patients after total knee arthroplasty (TKA). Anti-inflammatory medications may target arthrofibrosis pathogenesis, but the data are limited. This multicenter randomized clinical trial investigated the effect of adjuvant anti-inflammatory medications with MUA and physical therapy on range of motion (ROM) and outcomes. METHODS: There were 124 patients (124 TKAs) who developed stiffness after primary TKA for osteoarthritis enrolled across 15 institutions. All received MUA when ROM was < 90° at 4 to 12 weeks postoperatively. Randomization proceeded via a permuted block design. Controls received MUA and physical therapy, while the treatment group also received one dose of pre-MUA intravenous dexamethasone (8 mg) and 14 days of oral celecoxib (200 mg). The ROM and clinical outcomes were assessed at 6 weeks and 1 year. This trial was registered with ClinicalTrials.gov. RESULTS: The ROM significantly improved a mean of 46° from a pre-MUA ROM of 72 to 118° immediately after MUA (P < .001). The ROM was similar between the treatment and control groups at 6 weeks following MUA (101 versus 99°, respectively; P = .35) and at one year following MUA (108 versus 108°, respectively; P = .98). Clinical outcomes were similar at both end points. CONCLUSIONS: In this multicenter randomized clinical trial, the addition of intravenous dexamethasone and a short course of oral celecoxib after MUA did not improve ROM or outcomes. However, MUA provided a mean ROM improvement of 46° immediately, 28° at 6 weeks, and 37° at 1 year. Further investigation in regards to dosing, duration, and route of administration of anti-inflammatory medications remains warranted. LEVEL OF EVIDENCE: Level 1, RCT.

New Ceramic Heads With Titanium Sleeves on Retained Femoral Components: Results of Over 500 Revision Total Hip Arthroplasties.

BACKGROUND: Ceramic heads are frequently combined with titanium sleeves in revision total hip arthroplasties (THAs), ostensibly to protect the ceramic head from existing damage to the retained trunnion. Although widely adopted, data on the performance and safety of this construct are minimal. The purpose of this study was to describe implant survivorships, radiographic results, and clinical outcomes of patients who underwent revision THA with a ceramic head and titanium sleeve on a retained femoral component. METHODS: We identified 516 revision THAs with femoral component retention (328 acetabular-only revisions and 188 bearing surface exchanges) treated with a new ceramic head and titanium sleeve between 2000 and 2020. Mean age at revision was 64 years, 56% were women, and mean body mass index was 30. The indications for revision THA were adverse local tissue reaction (25%), acetabular loosening (24%), dislocation (17%), infection (5%), and other (29%). Kaplan-Meier survivorships were analyzed, radiographs reviewed, and Harris Hip Scores evaluated. Mean follow-up was 4 years (range, 2 to 10). RESULTS: There were no reoperations or failures for ceramic head fracture, taper corrosion, or head/sleeve disengagement. The 10-year survivorship free of any re-revision was 85%. Indications for the 57 re-revisions included dislocation (33), infection (13), acetabular component loosening (7), periprosthetic fracture (2), psoas impingement (1), and sciatic nerve irritation (1). The 10-year survivorship free of any reoperation was 82%. There were an additional 14 reoperations. Radiographically, 1.9% had progressive femoral radiolucent lines, and 4.7% had progressive acetabular radiolucent lines. Mean Harris Hip Score was 81 at 2 years. CONCLUSIONS: New ceramic heads with titanium sleeves in revision THAs with retained femoral components were durable and reliable with no cases of ceramic head fracture or taper complications at mean 4-year follow-up, including those revised for adverse local tissue reaction. LEVEL OF EVIDENCE: IV.

Platelet-derived growth factor receptor beta is required for embryonic specification and confinement of the adult white adipose lineage.

White adipose tissue (WAT) development and adult homeostasis rely on distinct adipocyte progenitor cells (APCs). While adult APCs are defined early during embryogenesis and generate adipocytes after WAT organogenesis, the mechanisms underlying adult adipose lineage determination and preservation remain undefined. Here, we uncover a critical role for platelet-derived growth factor receptor beta (Pdgfrß) in identifying the adult APC lineage. Without Pdgfrß, APCs lose their adipogenic competency to incite fibrotic tissue replacement and inflammation. Through lineage tracing analysis, we reveal that the adult APC lineage is lost and develops into macrophages when Pdgfrß is deleted embryonically. Moreover, to maintain the APC lineage, Pdgfrß activation stimulates p38/MAPK phosphorylation to promote APC proliferation and maintains the APC state by phosphorylating peroxisome proliferator activated receptor gamma (Pparγ) at serine 112. Together, our findings identify a role for Pdgfrß acting as a rheostat for adult adipose lineage confinement to prevent unintended lineage switches.

Whole Blood Metal Levels in the Setting of an Oncologic Endoprosthesis: Is There Cause for Concern?

BACKGROUND: Massive modular endoprostheses have become a primary means of reconstruction after oncologic resection of a lower extremity tumor. These implants are commonly made with cobalt-chromium alloys that can undergo wear and corrosion, releasing cobalt and chromium ions into the surrounding tissue and blood. However, there are few studies about the blood metal levels in these patients. QUESTION/PURPOSE: What is the whole blood cobalt and chromium ion level in patients with massive modular endoprostheses? METHODS: We performed a cross-sectional study of our total joints registry to identify patients with a history of an endoprosthetic reconstruction performed at our institution. Patients who were alive at the time of our review in addition to those undergoing an endoprosthetic reconstruction after an oncologic resection were included. Whole blood samples were obtained from 27 (14 male and 13 female) patients with a history of a lower extremity oncologic endoprosthesis. The median time from surgery to blood collection was 8 years (range 6 months to 32 years). Blood samples were collected and stored in metal-free ethylenediaminetetraacetic acid tubes. Samples were analyzed on an inductively coupled plasma mass spectrometer in an International Organization for Standardization seven-class clean room using polytetrafluoroethylene-coated instruments to reduce the risk of metal contamination. The analytical measuring range was 1 to 200 ng/mL for chromium and cobalt. Cobalt and chromium levels were considered elevated when the blood level was ≥ 1 ppb. RESULTS: Cobalt levels were elevated in 59% (16 of 27) of patients, and chromium levels were elevated in 26% (seven of 27). In patients with elevated metal ion values, 15 of 17 patients had a reconstruction using a Stryker/Howmedica Global Modular Replacement System implant. CONCLUSION: Blood metal levels were elevated in patients who received reconstructions using modular oncology endoprostheses Future work is needed to establish appropriate follow-up routines and determine whether and when systemic complications occur because of elevated metal levels and how to potentially address these elevated levels when complications occur. Prospective and retrospective collaboration between multiple centers and specialty societies will be necessary to address these unknown questions in this potentially vulnerable patient group. LEVEL OF EVIDENCE: Level IV, therapeutic study.