Citations

Objective Cartilage formation is stimulated in mixtures of chondrocytes and human adipose–derived mesenchymal stromal cells (MSCs) both in vitro and in vivo. During coculture, human MSCs perish. The goal of this study is to elucidate the mechanism by which adipose tissue–derived MSC cell death occurs in the presence of chondrocytes. Methods Human primary chondrocytes were cocultured with human MSCs derived from 3 donors. The cells were cultured in monoculture or coculture (20% chondrocytes and 80% MSCs) in pellets (200,000 cells/pellet) for 7 days in chondrocyte proliferation media in hypoxia (2% O 2 ). RNA sequencing was performed to assess for differences in gene expression between monocultures or coculture. Immune fluorescence assays were performed to determine the presence of caspase-3, LC3B, and P62. Results RNA sequencing revealed significant upregulation of >90 genes in the 3 cocultures when compared with monocultures. STRING analysis showed interconnections between >50 of these genes. Remarkably, 75% of these genes play a role in cell death pathways such as apoptosis and autophagy. Immunofluorescence shows a clear upregulation of the autophagic machinery with no substantial activation of the apoptotic pathway. Conclusion In cocultures of human MSCs with primary chondrocytes, autophagy is involved in the disappearance of MSCs. We propose that this sacrificial cell death may contribute to the trophic effects of MSCs on cartilage formation.

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

Background: Evidence-based, procedure-specific guidelines for prescribing opioids are urgently needed to optimize pain relief while minimizing excessive opioid prescribing and potential opioid diversion in our communities. A multidisciplinary panel at our institution recently developed procedure-specific guidelines for discharge opioid prescriptions for common orthopaedic surgical procedures. The purpose of this study was to evaluate postoperative opioid prescription quantities, variability, and 30-day refill rates before and after implementation of the guidelines. Methods: This retrospective cohort study was conducted at a single academic institution from December 2016 to March 2018. Guidelines were implemented on August 1, 2017, with a recommended maximum opioid prescription quantity for 14 common orthopaedic procedures. Patients who underwent these 14 procedures during the period of December 2016 to May 2017 made up the pre-guideline cohort (n = 2,223), and patients who underwent these procedures from October 2017 to March 2018 made up the post-guideline cohort (n = 2,300). Opioid prescription quantities were reported as oral morphine equivalents (OME), with medians and interquartile ranges (IQRs). Four levels were established for recommended prescription maximums, ranging from 100 to 400 OME. Results: In the pre-guideline cohort, the median amount of prescribed opioids across all procedures was 600 OME (IQR, 390 to 863 OME), which decreased by 38% in the post-guideline period, to a median of 375 OME (IQR, 239 to 400 OME) in the post-guideline cohort (p < 0.001). The 30-day refill rate did not change significantly, from a rate of 24% in the pre-guideline cohort to 25% in the post-guideline cohort (p = 0.43). Multivariable analysis demonstrated that guideline implementation was the factor most strongly associated with prescriptions exceeding guideline maximums (odds ratio [OR] = 9.9; p < 0.001). Age groups of <80 years (OR = 2.0 to 2.4; p < 0.001) and males (OR = 1.2; p = 0.025) were also shown to have higher odds of exceeding guideline maximums. Conclusions: Procedure-specific guidelines are capable of substantially decreasing opioid prescription amounts and variability. Furthermore, the absence of change in refill rates suggests that pain control remains similar to pre-guideline prescribing practices. Evidence-based guidelines are a readily employable solution that can drive rapid change in practice and enhance the ability of orthopaedic surgeons to provide responsible pain management.

AbstractBackground and ObjectivesThe ACS‐NSQIP surgical risk calculator is an online tool that estimates the risk of postoperative complications. Sacrectomies for chordoma are associated with a high rate of complications. This study was to determine if the ACS‐NSQIP calculator can predict postoperative complications following sacrectomy.MethodsSixty‐five (42 male, 23 female) patients who underwent sacrectomy were analyzed using the Current Procedural Terminology (CPT) codes: 49215 (excision of presacral/sacral tumor), 63001 (laminectomy of sacral vertebrae), 63728 (laminectomy for biopsy/excision of sacral neoplasm) and 63307 (sacral vertebral corpectomy for intraspinal lesion). The predicted rates of complications were compared to the observed rates.ResultsComplications were noted in 44 (68%) patients. Of the risk factors available to input to the ACS‐NSQIP calculator, tobacco use (OR, 20.4; P < .001) was predictive of complications. The predicted risk of complications based off the CPT codes were: 49215 (16%); 63011 (6%); 63278 (11%) and 63307 (15%). Based on ROC curves, the use of the ACS‐NSQIP score were poor predictors of complications (49215, AUC 0.65); (63011, AUC 0.66); (63307, AUC 0.67); (63278, AUC 0.64).ConclusionThe ACS‐NSQIP calculator was a poor predictor of complications and was marginally better than a coin flip in its ability to predict complications following sacrectomy for chordoma.

AbstractBackgroundConventional primary pelvic chondrosarcoma often presents as a low‐ or intermediate‐grade tumor in older patients. Although this is the most common variant of pelvic chondrosarcoma, studies examining treatment outcomes are lacking. The purpose of this study was to evaluate patients with these tumors to determine their outcomes of treatment.MethodsSeventy‐three patients (grade I [n = 19, 26%] and grade II [n = 54, 74%]) were reviewed including 55 (75%) males and 18 (25%) females, with a mean age of 51 (range, 17‐81) years and follow‐up of 9 ± 5 years.ResultsThe 10‐year disease‐specific survival was 71%. Grade II disease (hazard ratio [HR], 6.74; P = .04) and age ≥50 years (HR, 3.97; P = .02) was associated with death due to disease. The 10‐year local recurrence‐ and metastatic‐free survival were 79% and 72%. Of the patients with a local recurrence (n = 11), 7 (64%) recurred at a higher histological grade. Patient age ≥50 years was associated with local recurrence (HR, 10.03; P = .02) and metastatic disease (HR, 4.20; P = .02).ConclusionAdvancing patient age was an independent risk factor for worse survival and disease recurrence. Tumors often recurred locally at a higher grade and as such wide local excision remains the treatment of choice for these tumors.

Background: Periacetabular osteotomy (PAO) can be used for joint preservation in symptomatic developmental dysplasia of the hip (DDH) and femoroacetabular impingement (FAI). 1 of the most common procedures following PAO is hardware removal. The aims of this study were to determine the rate of hardware removal and patient characteristics associated with this outcome following PAO. Methods: Data from a prospectively-collected registry was retrospectively reviewed at one institution managing DDH or FAI patients with PAO from July 2008–December 2015. Patients who completed preoperative and postoperative patient reported outcome (PRO) questionnaires with minimum 1-year follow-up were evaluated, resulting in 221 patients followed for a mean of 2.8 years (range 1.0–7.7 years). There were 80% women, mean age was 25 years and mean body mass index (BMI) was 25 kg/m 2 . Fully-threaded 4.5-mm screws were used for internal fixation. Results: Hardware removal occurred in 30 patients (13.6%) at a mean of 1.0 years after PAO. Patients undergoing hardware removal were younger (mean age 20.4 vs. 26.3 years), thinner (mean BMI 22.2 vs. 25.1), had less severe dysplasia (DDH patients only: mean lateral centre-edge angle 21.0 vs. 16.2, mean Tönnis angle 12.9 vs. 16.8), and were more likely to have PAO for FAI (33% vs. 11%) compared to patients with retained hardware. At final follow-up, multivariable analysis demonstrated a trend toward inferior patient reported outcomes in the hardware removal group. Conclusions: This study defines the incidence and characteristics of patients undergoing hardware removal after PAO and demonstrates similar outcomes to patients who do not require hardware removal.

Objective. Osteochondral allograft (OCA) transplantation has demonstrated good long-term outcomes in treatment of cartilage defects. Viability, a key factor in clinical success, decreases with peri-implantation storage at 4°C during pathogen testing, matching logistics, and transportation. Modern, physiologic storage conditions may improve viability and enhance outcomes. Design. Osteochondral specimens from total knee arthroplasty patients (6 males, 5 females, age 56.4 ± 2.2 years) were stored in media and incubated at normoxia (21% O 2 ) at 22°C or 37°C, and hypoxia (2% O 2 ) at 37°C. Histology, live-dead staining, and quantitative polymerase chain reaction (qPCR) was performed 24 hours after harvest and following 7 days of incubation. Tissue architecture, cell viability, and gene expression were analyzed. Results. No significant viability or gene expression deterioration of cartilage was observed 1-week postincubation at 37°C, with or without hypoxia. Baseline viable cell density (VCD) was 94.0% ± 2.7% at day 1. At day 7, VCD was 95.1% (37°C) with normoxic storage and 92.2% (37°C) with hypoxic storage ( P ≥ 0.27). Day 7 VCD (22°C) incubation was significantly lower than both the baseline and 37°C storage values (65.6%; P < 0.01). COL1A1, COL1A2, and ACAN qPCR expression was unchanged from baseline ( P < 0.05) for all storage conditions at day 7, while CD163 expression, indicative of inflammatory macrophages and monocytes, was significantly lower in the 37°C groups ( P < 0.01). Conclusion. Physiologic storage at 37°C demonstrates improved chondrocyte viability and metabolism, and maintained collagen expression compared with storage at 22°C. These novel findings guide development of a method to optimize short-term fresh OCA storage, which may lead to improved clinical results.

AbstractBackgroundLocal recurrence (LR) of sacral chordoma is a difficult problem and the mortality risk associated with LR remains poorly described. The purpose of this study was to evaluate the risk of mortality in patients with LR and determine if patient age is associated with mortality.MethodsA total of 218 patients (144 male, 69 female; mean age 59 ± 15 years) with sacrococcygeal chordomas were reviewed. Cumulative incidence functions and competing risks for death due to disease and nondisease mortality were employed to analyze mortality trends following LR.ResultsThe 10‐year overall survival (OS) was 55%. Patients with LR had 44% 10‐year OS, similar to patients without (59%; P = .38). The 10‐year OS between those less than 55 compared with ≥55 years were similar (69% vs 48%; P = .52). The 10‐year death due to disease was worse in patients with LR compared with those without (44% vs 84%; P < .001). In patients without LR, patients ≥55 years were 1.6‐fold more likely to experience death due to other causes.ConclusionsPatients with an LR are more likely to die due to disease. Advanced patient age was associated with higher all‐cause mortality following resection of sacral chordoma. LR of chordoma was associated with increased disease‐specific mortality, regardless of age.

Objective This study aims to (1) determine and validate living cartilage allograft transplantation as a novel source for viable osteochondral allograft (OCA) tissues and (2) perform histologic and viability comparisons of living donor cartilage tissues to currently available clinical-grade standard processed grafts. Design Using healthy cartilage from well-preserved contralateral compartments in 27 patients undergoing total knee arthroplasty (TKA) and 10 clinical-grade OCA specimens obtained immediately following operative implantation, standard and living donor OCA quality was evaluated at the time of harvest and following up to 3 weeks of storage on the basis of macroscopic International Cartilage Repair Society grade, histology, and viability. Results Osteochondral samples demonstrated a consistent decrease in viability and histologic quality over the first 3 weeks of storage at 37°C, supporting the utility of an OCA paradigm shift toward early implantation, as was the clinical standard up until recent adoption of transplantation at 14 to 35 days following donor procurement. Samples from the 10 clinical-grade OCAs, implanted at an average of 23 days following graft harvest demonstrated a mean viable cell density of 45.6% at implantation, significantly lower ( P < 0.01) than the 93.6% viability observed in living donor allograft tissues. Conclusions Osteochondral tissue viability and histologic quality progressively decreases with ex vivo storage, even when kept at physiologic temperatures. Currently available clinical OCAs are stored for 2 to 5 weeks prior to implantation and demonstrate inferior viability to that of fresh osteochondral tissues that can be made available through the use of a living donor cartilage program.

Abstract Meniscus tears are commonly encountered in the clinical and operative setting and vary in presentation, including bucket‐handle, radial, and horizontal cleavage tears. Historically, tears were treated with benign neglect or partial meniscectomy. However, a great deal of subsequent research has highlighted the biomechanical consequences of tears and meniscectomy, including increased peak local contact forces, progressive postmeniscectomy arthritis, and subsequent arthroplasty. With the advent and evolution of repair devices, increasing attention is being turned to the ideal restorative treatment of meniscus tears. Successful meniscus repair is centered about the ABCs of repair: Anatomic reduction, Biologic preparation and augmentation, and Circumferential compression. Recent advances in repair techniques have included microfracture of the intercondylar notch to provide healing factors and marrow cells for augmented healing, all‐inside suture devices enabling the reduction and fixation tears without the need for additional assistants and the morbidity of inside‐out exposure, and circumferential compression combined with clot augmentation to reduce and fix horizontal cleavage tears and recreate biomechanics to within 15% of baseline contact forces. Clinical outcomes of meniscus repair using modern techniques have been promising, with reapproximation of native joint biomechanics, substantial improvements in patient subjective outcome scores, and satisfactory reoperation rates. With implementation of the ABCs of meniscus repair as well as the continued expansion of the orthopedic surgeons' meniscus repair toolbox, restoration and preservation of the meniscus are increasingly possible across the spectrum of tear types.