Citations

AimsDislocation 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.MethodsWe 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).ResultsThere 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.ConclusionWhile 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.Cite this article: Bone Joint J 2024;106-B(4):352–358.

AimsBreast 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.MethodsOur 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).ResultsBreast 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).ConclusionBreast 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.Cite this article: Bone Joint J 2024;106-B(4):365–371.

AbstractBackgroundFor many patients with lung disease the only proven intervention to improve survival and quality of life is lung transplantation (LTx). Esophageal dysmotility and gastroesophageal reflux (GER) are common in patients with respiratory disease, and often associate with worse prognosis following LTx. Which, if any patients, should be excluded from LTx based on esophageal concerns remains unclear. Our aim was to understand the effect of LTx on esophageal motility diagnosis and examine how this and the other physiological and mechanical factors relate to GER and clearance of boluses swallowed.MethodsWe prospectively recruited 62 patients with restrictive (RLD) and obstructive (OLD) lung disease (aged 33–75 years; 42 men) who underwent high resolution impedance manometry and 24‐h pH‐impedance before and after LTx.Key ResultsRLD patients with normal motility were more likely to remain normal (p = 0.02), or if having abnormal motility to change to normal (p = 0.07) post‐LTx than OLD patients. Esophageal length (EL) was greater in OLD than RLD patients' pre‐LTx (p < 0.001), reducing only in OLD patients' post‐LTx (p = 0.02). Reduced EL post‐LTx associated with greater contractile reserve (r = 0.735; p = 0.01) and increased likelihood of motility normalization (p = 0.10). Clearance of reflux improved (p = 0.01) and associated with increased mean nocturnal baseline impedance (p < 0.001) in RLD but not OLD. Peristaltic breaks and thoraco‐abdominal pressure gradient impact both esophageal clearance of reflux and boluses swallowed (p < 0.05).Conclusions and InferencesRLD patients are more likely to show improvement in esophageal motility than OLD patients post‐LTx. However, the effect on GER is more difficult to predict and requires other GI, anatomical and pulmonary factors to be taken into consideration.

Abstract Background: Analyzing interactions and the microanatomical distribution of the tumor immune microenvironment (TIME) is essential for a comprehensive understanding of tumor progression. Imaging Mass Cytometry (IMC) is a high-dimensional tissue imaging system that enables the deeper and multiparametric in situ exploration of tumor microenvironments at a single-cell level. This study describes a pipeline for analyzing 39-plex IMC images of human HPV(+) oropharyngeal squamous cell carcinoma (OPSCC) tumor sections, elucidating immune cells' nature, functions, and interactions with tumor cells. The IMC data analysis provides valuable information for clinical studies that could be used for the identification of prognostic biomarkers and mechanisms of resistance to current immunotherapies. Methods: A retrospective study was conducted on (N=20) patients (10 progressors and 10 non-progressors) with HPV(+) OPSCC. The dataset comprises paired hematoxylin and eosin (H&E) images with IMC data from multiple Regions of Interest (ROIs) (N=82), enabling the in-situ profiling of 39 proteins in primary tumor tissue. Cell segmentation was followed by employing original images and their segmentation masks for cell phenotype identification using a probabilistic neural network method to spatially profile cancer cells, macrophages, NK-M cells, B-cells, and distinct T-cell populations. We identified protein expression at single-cell resolution and investigated the impact of multicellular spatial organization on the disease progression. The spatial neighborhood interaction score of tumor cells with various other cells was computed for all the ROIs across the two groups. Results: The markers showed varying expression levels of intensity distribution, likely due to differences in tissue sample composition. Specifically, CD3, CD4, CD8, CD19, CD20, and CD68 showed significantly higher intensity in non-progressors. Interestingly, FoxP3 also had a significantly higher intensity level in non-progressors. Cell phenotyping emphasized that non-progressors generally have increased levels of NK-M cell markers. Spatial analysis revealed a significant increase in interaction between CD3 cells and tumor cells in non-progressors (p-value=0.07, Mann-Whitney U test). Furthermore, a significant rise in the interaction between B-cells and FoxP3+ cells was observed in non-progressors (p-value&lt;0.05, Mann-Whitney U test) suggesting a coordinated suppression of tumor growth. Conclusion: We developed a deep learning-based pipeline to analyze spatial relationships in the TIME of IMC data, demonstrating its clinical relevance in predicting disease progression. Our findings emphasize the importance of spatial relationships in the TME for response and suggest that proximity between either CD3+ T-cells to cancer cells or B-cells to FoxP3+ cells are candidate biomarkers. Citation Format: Sumanth Reddy Nakkireddy, Routman David, Kathleen Bartemes, Daniel Ma, Tae Hyun Hwang, Kathryn Van Abel, Chadi Nimeh Abdel-Halim. AI-enhanced spatial proteomics reveals B-cells & FoxP3+ cells interactions in HPV(+) oropharyngeal squamous cell carcinoma Progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5488.

Abstract Introduction Implant sonication is useful for recovery of periprosthetic joint infection (PJI) pathogens in culture, but exact cutoff points for definition of clinically significant sonicate fluid culture results vary from study to study. The aim of this study was to define ideal sonicate fluid culture cutoff points for PJI diagnosis. Methods Sonicate fluid cultures from hip and knee prosthesis components removed between February 2007 and December 2020 were studied. Prosthesis components were placed in solid containers in the operating room; in the clinical microbiology laboratory, 400 mL Ringer's solution was added, and containers subjected to vortexing, sonication and then vortexing, followed by centrifugation. Concentrated sonicate fluid was plated on aerobic and anaerobic solid media, and culture results reported semiquantitatively, as no growth, &lt;20, 20–50, 51–100, or &gt;100 CFU/10 mL sonicate fluid. Sonicate cultures from cement spacers and cultures yielding more than 1 microorganism were excluded. Sensitivity and specificity of each cutoff point was evaluated. Results A total of 1448 sonicate fluid cultures were evaluated, 68% from knees and 32% from hips. PJI was present in 644 (44%) cases. Sensitivity of sonicate culture was 75.0% at &lt;20 CFU/10 mL, 55.3% at ≥20 CFU/10 mL, 46.9% at &gt;51 CFU/10 mL, and 39.8% at &gt;100 CFU/10 mL. Specificity was 78.2%, 99.8%, 100%, and 100%, at the 4 cutoff points, respectively. Conclusions A cutoff point for sonicate fluid culture positivity of ≥20 CFU/10 mL is suitable for PJI diagnosis.

Introduction The Pipeline Embolization Device (PED) is commonly used for intracranial aneurysm treatment. While its effectiveness for certain types of aneurysms is well‐established, its efficacy for saccular aneurysms remains debatable. This review and meta‐analysis aimed to assess the long‐term outcomes of PED treatment for unruptured intracranial aneurysms (UIA). Methods A systematic review and meta‐analysis were conducted following PRISMA guidelines. Studies with at least one year of follow‐up after PED treatment for saccular aneurysms were included. The primary endpoint was angiographic complete aneurysm occlusion at long‐term (≥ 12 mo.) follow‐up. Secondary outcomes included long‐term complications. We conducted a meta‐regression analysis to explore the potential sources of heterogeneity across studies. Results Eleven studies on 594 patients with 726 aneurysms were included, of which 5% were previously treated. The mean age was 55.7 years, and 78.3% were women. The mean aneurysm size was 7.72 mm, 8.95% were treated with more than one device, and 2.9% had adjunct coiling. The long‐term complete occlusion rate was 81% (CI 95%: 72% to 88%, p<0.01). Regarding long‐term complications, the rate of symptomatic ischemic stroke was 1% (CI 95%: 0% to 4%, p=0.07), the rate of delayed rupture was 1% (95%, CI 0% to 3%, p=0.02), and the rate of intracranial hemorrhage was 3% (CI 95%: 1% to 6%, p=0.81). The meta‐regression analysis revealed a decreasing trend per year for aneurysmal occlusion, ischemic stroke rate, and aneurysmal rupture rate over time and an increasing trend for ICH over time. Conclusion PED demonstrates high long‐term occlusion and low complication rates, suggesting it is a safe and effective treatment option for unruptured intracranial saccular aneurysms. However, studies with greater than 5‐10 years of follow‐up are needed to evaluate the clinical and radiographical outcomes of incompletely occluded aneurysms Additionally, as newer devices exhibit reduced thrombogenic profiles and ICH rates increase over time, reevaluation of antiplatelet therapy's role, including dosage and DAPT, is warranted.

Summary Non‐steroidal anti‐inflammatory drugs (NSAIDs) are one of the mainstays of multimodal pain management. While effective for acute pain control, recent pre‐clinical evidence has raised concerns regarding an association between NSAIDs and chronic pain and potential opioid use. Our objective was to explore the association between peri‐operative use of prescription NSAIDs and the need for continued opioid prescriptions lasting 90–180 days in previously opioid‐naïve patients undergoing total knee arthroplasty. A database of health claims in the USA was used to identify all opioid‐naïve adult patients who underwent primary knee arthroplasty between January 2010 and October 2021. We evaluated the magnitude of association between peri‐operative prescription NSAID claims and claims for opioids at 90 days postoperatively using multivariable logistic regression models. Secondary outcomes included: the magnitude of association between peri‐operative NSAID prescription and claims for opioids at 180 days postoperatively; and identifying other potential factors associated with opioid claims at 90 days postoperatively. After risk adjustment using multivariable logistic regression models in the 789,736‐patient cohort, the adjusted odds ratio (95%CI) for a continuous claim of opioids at 90 and 180 days postoperatively among patients with a peri‐operative NSAID prescription within 30 days was 1.32 (1.30–1.35), p < 0.001; and 1.12 (1.10–1.15), p < 0.001, respectively. This estimate of effect remained robust at 90 days after accounting for known potential confounders, including pre‐existing knee pain and acute postoperative pain severity. Similar analysis of other pain medications (e.g. paracetamol) did not detect such an association. This population‐based cohort study suggests that peri‐operative prescription NSAID use may be associated with continued opioid prescription claims at 90 and 180 days after knee arthroplasty, even after adjusting for other observed covariates for continuous opioid claims. These novel findings can inform clinical decision‐making for post‐surgical pain management, risk–benefit discussions with patients and future research.

Marlex mesh reconstruction of the extensor mechanism following total knee arthroplasty (TKA) has demonstrated excellent early results. The purpose of the present study was to evaluate longer-term results of Marlex mesh reconstruction of the extensor mechanism in 93 TKAs. Seventy-seven reconstructions were aseptic, and 16 were performed as part of a 2-stage exchange for the treatment of infection. Mean follow-up was 8 years. Twenty-eighty patients experienced mesh failure. Seventeen failures were treated with mesh revision (8 for patellar tendon rupture, 7 for quadriceps tendon rupture, and 2 for symptomatic lengthening). The 10-year cumulative incidence of mesh revision for mesh failure was 20%. Extensor lag improved by a mean of 28°, with a mean extensor lag of 9° at most recent follow-up. At a mean follow-up of 8 years, Marlex mesh reconstruction was a durable and reliable technique to treat both aseptic and septic ruptures of the extensor mechanism. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

AbstractArthrofibrosis, which causes joint motion restrictions, is a common complication following total knee arthroplasty (TKA). Key features associated with arthrofibrosis include myofibroblast activation, knee stiffness, and excessive scar tissue formation. We previously demonstrated that adiponectin levels are suppressed within the knee tissues of patients affected by arthrofibrosis and showed that AdipoRon, an adiponectin receptor agonist, exhibited anti‐fibrotic properties in human mesenchymal stem cells. In this study, the therapeutic potential of AdipoRon was evaluated on TGFβ1‐mediated myofibroblast differentiation of primary human knee fibroblasts and in a mouse model of knee stiffness. Picrosirius red staining revealed that AdipoRon reduced TGFβ1‐induced collagen deposition in primary knee fibroblasts derived from patients undergoing primary TKA and revision TKA for arthrofibrosis. AdipoRon also reduced mRNA and protein levels of ACTA2, a key myofibroblast marker. RNA‐seq analysis corroborated the anti‐myofibrogenic effects of AdipoRon. In our knee stiffness mouse model, 6 weeks of knee immobilization, to induce a knee contracture, in conjunction with daily vehicle (DMSO) or AdipoRon (1, 5, and 25 mg/kg) via intraperitoneal injections were well tolerated based on animal behavior and weight measurements. Biomechanical testing demonstrated that passive extension angles (PEAs) of experimental knees were similar between vehicle and AdipoRon treatment groups in mice evaluated immediately following immobilization. Interestingly, relative to vehicle‐treated mice, 5 mg/kg AdipoRon therapy improved the PEA of the experimental knees in mice that underwent 4 weeks of knee remobilization following the immobilization and therapy. Together, these studies revealed that AdipoRon may be an effective therapeutic modality for arthrofibrosis.