Citations

Abstract Context SDHB mutations are found in an increasing number of neoplasms, most notably in paragangliomas and pheochromocytomas (PPGLs). SDHB-PPGLs are slow-growing tumors, but ∼50% of them may develop metastasis. The molecular basis of metastasis in these tumors is a long-standing and unresolved problem. Thus, a better understanding of the biology of metastasis is needed. Objective This study aimed to identify gene methylation changes relevant for metastatic SDHB-PPGLs. Design We performed genome-wide profiling of DNA methylation in diverse clinical and genetic PPGL subtypes, and validated protocadherin γ-C3 (PCDHGC3) gene promoter methylation in metastatic SDHB-PPGLs. Results We define an epigenetic landscape specific for metastatic SDHB-PPGLs. DNA methylation levels were found significantly higher in metastatic SDHB-PPGLs than in SDHB-PPGLs without metastases. One such change included long-range de novo methylation of the PCDHA, PCDHB, and PCDHG gene clusters. High levels of PCDHGC3 promoter methylation were validated in primary metastatic SDHB-PPGLs, it was found amplified in the corresponding metastases, and it was significantly correlated with PCDHGC3 reduced expression. Interestingly, this epigenetic alteration could be detected in primary tumors that developed metastasis several years later. We also show that PCDHGC3 down regulation engages metastasis-initiating capabilities by promoting cell proliferation, migration, and invasion. Conclusions Our data provide a map of the DNA methylome episignature specific to an SDHB-mutated cancer and establish PCDHGC3 as a putative suppressor gene and a potential biomarker to identify patients with SDHB-mutated cancer at high risk of metastasis who might benefit from future targeted therapies.

Aims The aims of this study were to characterize antibiotic choices for perioperative total knee arthroplasty (TKA) and total hip arthroplasty (THA) prophylaxis, assess antibiotic allergy testing efficacy, and determine rates of prosthetic joint infection (PJI) based on perioperative antibiotic regimen. Patients and Methods We evaluated all patients undergoing primary TKA or THA at a single academic institution between January 2004 and May 2017, yielding 29 695 arthroplasties (22 705 patients), with 3411 arthroplasties in 2576 patients (11.5%) having undergone preoperative allergy testing. A series of institutional databases were combined to identify allergy consultation outcomes, perioperative antibiotic regimen, and infection-free survivorship until final follow-up. Results Among 2576 allergy-tested patients, 2493 patients (97%) were cleared to use cephalosporins. For the entire cohort, 28 174 arthroplasties (94.9%) received cefazolin and 1521 (5.1%) received non-cefazolin antibiotics. Infection-free survivorship was significantly higher among arthroplasties receiving cefazolin compared with non-cefazolin antibiotics, with 0.06% higher survival free of infection at one month, 0.56% at two months, 0.61% at one year, and 1.19% at ten years (p < 0.001). Overall, the risk of PJI was 32% lower in patients treated with cefazolin after adjusting for the American Society of Anesthesiologists (ASA) classification, joint arthroplasty (TKA or THA), and body mass index (BMI; p < 0.001). The number needed to treat with cefazolin to prevent one PJI was 164 patients at one year and 84 patients at ten years. Therefore, potentially 6098 PJIs could be prevented by one year and 11 905 by ten years in a cohort of 1 000 000 primary TKA and THA patients. Conclusion PJI rates are significantly higher when non-cefazolin antibiotics are used for perioperative TKA and THA prophylaxis, highlighting the positive impact of preoperative antibiotic allergy testing to increase cefazolin usage. Given the low rate of true penicillin allergy positivity, and the readily modifiable risk factor that antibiotic choice provides, we recommend perioperative testing and clearance for all patients presenting with penicillin and cephalosporin allergies. Cite this article: Bone Joint J 2019;101-B(6 Supple B):9–15.

Background: Anterior cruciate ligament (ACL) injury is one of the most frequent orthopaedic injuries and reasons for time loss in sports and carries significant implications, including posttraumatic osteoarthritis (OA). Instability associated with ACL injury has been linked to the development of secondary meniscal tears (defined as tears that develop after the initial ACL injury). To date, no study has examined secondary meniscal tears after ACL injury and their effect on OA and arthroplasty risk. Purpose: To describe the rates and natural history of secondary meniscal tears after ACL injury and to determine the effect of meniscal tear treatment on the development of OA and conversion to total knee arthroplasty (TKA). Study Design: Cohort study; Level of evidence, 3. Methods: A geographic database of >500,000 patients was reviewed to identify patients with primary ACL injuries between January 1, 1990, and December 31, 2005. Information was collected with regard to ACL injury treatment, rates/characteristics of the secondary meniscal tears, and outcomes, including development of OA and conversion to TKA. Kaplan-Meier and adjusted multivariate survival analyses were performed to test for the effect of meniscal treatment on survivorship free of OA and TKA. Results: Of 1398 primary ACL injuries, the overall rate of secondary meniscal tears was 16%. Significantly lower rates of secondary meniscal tears were noted among patients undergoing acute ACL reconstruction within 6 months (7%) as compared with patients with delayed ACL reconstruction (33%, P < .01) and nonoperative ACL management (19%, P < .01). Of the 235 secondary meniscal tears identified (196 patients), 11.5% underwent repair, 73% partial meniscectomy, and 16% were treated nonoperatively. Tears were most often medial in location (77%) and complex in morphology (56% of medial tears, 54% of lateral tears). At the time of final follow-up, no patient undergoing repair of a secondary meniscal tear (0%) underwent TKA, as opposed to 10.9% undergoing meniscectomy and 6.1% receiving nonoperative treatment ( P = .28). Conclusion: Secondary meniscal tears after ACL injury are most common among patients undergoing delayed surgical or nonoperative treatment of their primary ACL injuries. Secondary tears often present as complex tears of the medial meniscus and result in high rates of partial meniscectomy.

3501 Background: 6m of oxaliplatin-based treatment is an option as adj chemotherapy for patients with high risk stage II CC (T4, inadequate nodal harvest, poorly differentiated, obstruction, perforation or vascular/perineural invasion). The IDEA collaboration showed shorter treatment duration to be appropriate for most pts with stage III colon cancer. The results of the 4 IDEA studies with stage II pts are presented here. Methods: A prospective, pre-planned pooled analysis of high-risk stage II patients from 4 concurrently conducted randomized phase III trials (SCOT, TOSCA, ACHIEVE-2, HORG) was performed to evaluate non-inferiority (NI) of 3m compared with 6m (ref) of adj FOLFOX/CAPOX (regimen preselected, not randomized). The primary endpoint was disease-free survival (DFS), NI was to be declared if the 2-sided 80% confidence interval (CI) for DFS hazard ratio (HR 3m v 6m) estimated by a stratified Cox model was below 1.2. 542 DFS events were required to provide 80% power to declare NI. NI was also examined within regimen, T4 (Yes v No) and inadequate nodal harvest (Yes v No) as pre-planned subgroups. Results: The primary analysis included 3273 randomised pts of which 1254 had FOLFOX and 2019 had CAPOX. There were 552 events and the median follow-up was 60.2 m. There was significantly less grade 3-5 toxicity with 3m treatment (p < .0001). The 5-year DFS rate was 80.7% and 84.0% for 3m and 6m treatment with an estimated DFS HR of 1.18 (80% CI:1.05-1.31, p for NI = 0.404). For CAPOX the estimated HR was 1.02 (80% CI: 0.88-1.17, p for NI = 0.087) and for FOLFOX the estimated HR was 1.42 (80% CI: 1.19-1.70, p for NI = 0.894). The test for interaction between duration and regimen was not statistically significant (p = .174 adjusted for multiple testing) but was stronger than that for the other subgroups examined. Conclusions: In the overall population non-inferiority for 3m adj treatment in pts with high-risk stage II CC was not shown. As with the stage III population the choice of adj regimen appears important (although this did not reach statistical significance) with a small difference in DFS between 3 and 6 m treatment if CAPOX is used. Clinical trial information: ISRCTN59757862.

Abstract Focal cartilage defects lead to significant pain and disability, prompting the development of various options for biologic restoration of the articular surface. Although each technique and biologic implant provides various advantages and associated limitations, matrix‐induced autologous chondrocyte implantation (MACI) has gained popularity given promising long‐term results. We present a technique for the facile implantation of MACI membranes using cookie cutter instrumentation to aid in defect debridement and graft preparation. The technique described allows for efficient operative workflow while ensuring the creation of vertical, stable defect edges and a form‐fitting MACI membrane in a readily implemented fashion. Technique Video video See video under supplementary data.

Background: Revision total hip arthroplasty (revision THA) occurs for a wide variety of indications and in the United States it is coded under Diagnosis-Related Groups (DRGs) 466, 467, and 468, which do not account for revision etiology, a potentially substantial driver of cost. This study investigates revision THA costs and 30-day complications by indication, both locally and nationally. Methods: Hospitalization costs and complication rates for 1,422 aseptic revision THAs performed at a high-volume center between 2009 and 2014 were retrospectively reviewed. Additionally, charges for 28,133 revision THAs in the National Inpatient Sample (NIS) were converted to costs using the Healthcare Cost and Utilization Project cost-to-charge ratios, and 30-day complication rates for 3,224 revision THAs were obtained with use of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Costs and complications were compared between revision THAs performed for fracture, wear/loosening, and dislocation/instability with use of simultaneous and pairwise comparisons and a multivariable model accounting for American Society of Anesthesiologists (ASA) score, age, and sex. Results: Local hospitalization costs for fracture (median, $25,672) were significantly higher than those for wear/loosening ($20,228; p < 0.001) or dislocation/instability ($17,911; p < 0.001), with differences remaining significant even after adjusting for patient comorbidities (p < 0.001). NIS costs for fracture (median, $27,596) were higher than those for other aseptic indications (wear/loosening: $21,176, p < 0.001; dislocation/instability: $16,891, p< 0.001). Local 30-day orthopaedic complication rates for fracture (20.7%) were higher those than for dislocation/instability (9.0%; p = 0.007) and similar to those for wear/loosening (17.6%; p = 0.434). Nationally, combined medical and surgical complication rates for fracture (71.3% of patients with ≥1 complication) were significantly higher than those for wear/loosening (35.2%; p < 0.001) or dislocation/instability (35.1%; p < 0.001). Conclusions: Hospitalization costs for revision THA for fracture were 33% to 48% higher than for all other aseptic revision THAs, both locally and nationally. This increased cost persisted even after multivariable comorbidity adjustment, the current DRG basis for stratifying revision THA reimbursement. Additionally, 30-day complication rates suggest that increased resource utilization for fracture patients continues even after discharge. Indication-specific coding and reimbursement systems are necessary to maintain sustainable access to revision THA for all patients. Level of Evidence: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Background: Hip arthroscopy is becoming more advanced and commonly performed. However, significant controversy exists regarding whether high-grade acetabular cartilage lesions should be treated with debridement/abrasion or microfracture. In addition, patients treated with microfracture are subject to extended protected weightbearing rehabilitation to mitigate risk of subchondral plate fracture and to protect fibrocartilage tissue formation. Purpose: To determine the midterm patient-reported outcomes and failure rate of patients with grade 3 and 4 acetabular labrum articular disruption (ALAD) lesions managed with debridement/abrasion or microfracture. Study Design: Cohort study; Level of evidence, 3. Methods: Primary arthroscopic labral repair cases at 2 centers from November 2008 to April 2016 were reviewed for patients aged <55 years with unipolar ALAD grade 3 and 4 chondrolabral acetabular delamination. Patients undergoing microfracture and debridement/abrasion were compared using the visual analog pain scale (VAS), modified Harris Hip Score (mHHS), and Hip Outcome Score–Sports-Specific Subscale (HOS-SSS) to determine predictors of outcomes and failure. Results: A total of 113 hips in 110 patients (66 males, 44 females; mean age, 34.5 ± 1.1 years) undergoing debridement/abrasion (n = 82) or microfracture (n = 31) were followed for a mean of 4.9 years (range, 2.0-8.5 years). Lesion size was not statistically different between the debridement/abrasion (1.3 ± 1.0 cm 2 ) and microfracture cohorts (1.4 ± 1.0 cm 2 ) ( P = .47). Patients undergoing debridement/abrasion achieved 3.6-point mean improvements in VAS ( P < .01), 21.2-point improvements in mHHS ( P < .01), and 25.4-point improvements in HOS-SSS ( P < .01), which were not significantly different from those observed in microfracture patients ( P≥ .20). The 5-year rate of survival free of revision surgery was 84.0% in the debridement/abrasion group and 85.6% in the microfracture group ( P = .78). The cartilage treatment technique was found not to be predictive of revision risk during both univariate (hazard ratio [HR], 1.01; P = .98) and multivariate (HR, 0.93; P = .90) analysis accounting for patient age, lesion grade, and acetabular coverage. Conclusion: Patients undergoing debridement/abrasion of high-grade unipolar acetabular cartilage lesions demonstrate similar outcome scores and revision rates compared with those of patients undergoing microfracture. These outcomes support the consideration of preferential debridement/abrasion at the discretion of the treating surgeon to optimize recovery while maintaining established positive outcomes after hip arthroscopy.