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Objectives: Obesity is a well-recognised risk factor for osteoarthritis (OA). Our aim is to characterise body mass index (BMI)-associated pathological changes in the osteochondral unit and determine if obesity is the major causal antecedent of early joint replacement in patients with OA., Methods: We analysed the correlation between BMI and the age at which patients undergo total knee replacement (TKR) in 41 023 patients from the Australian Orthopaedic Association National Joint Replacement Registry. We then investigated the effect of BMI on pathological changes of the tibia plateau of knee joint in a representative subset of the registry., Results: 57.58% of patients in Australia who had TKR were obese. Patients with overweight, obese class I & II or obese class III received a TKR 1.89, 4.48 and 8.08 years earlier than patients with normal weight, respectively. Microscopic examination revealed that horizontal fissuring at the osteochondral interface was the major pathological feature of obesity-related OA. The frequency of horizontal fissure was strongly associated with increased BMI in the predominant compartment. An increase in one unit of BMI (1 kg/m 2 ) increased the odds of horizontal fissures by 14.7%. 84.4% of the horizontal fissures were attributable to obesity. Reduced cartilage degradation and alteration of subchondral bone microstructure were also associated with increased BMI., Conclusions: The key pathological feature in OA patients with obesity is horizontal fissuring at the osteochondral unit interface. Obesity is strongly associated with a younger age of first TKR, which may be a result of horizontal fissures., Competing Interests: Competing interests: The conduct of work is supported by the general funding of the University of Western Australia. LC has received Scholarship for International Research Fees from the University of Western Australia. All authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of this study was to compare overall survival (OS) of women with advanced ovarian cancer treated with primary debulking surgery (PDS) or neoadjuvant chemotherapy (NAC) using a large national cohort., Methods: The 1998-2011 National Cancer Database was queried to identify women with stage III or IV ovarian cancer treated with multiagent chemotherapy and stage-appropriate surgery. Overall survival was estimated and compared using Kaplan-Meier analysis between women who received PDS followed by multiagent chemotherapy or NAC followed by interval surgery. Multivariable Cox proportional hazards regression model tested for associations of potential explanatory variables with OS. Analyzed confounders included age, composite comorbidity scores, stage, grade, histology, insurance status, income quartile, and race., Results: Overall, 44,907 women (85.9%) underwent PDS, and 7348 women (14.1%) received NAC. Women who received NAC were older (64 vs 61 years, P < 0.001), had higher comorbidity scores (P < 0.001), and more often had stage IV disease (44.1% vs 26.1%, P < 0.001). Median OS was 41.1 (40.5-41.7) months among women who underwent PDS compared with 30.3 (29.3-31.1) months among women who received NAC (log-rank, P < 0.001). Among women with stage III disease, PDS was associated with increased OS compared with NAC (median OS, 44.9 [44.2-45.7] vs 31.4 [30.2-33.0] months; hazard ratio [95% confidence interval], 0.70 [0.66-0.76]; P < 0.001). Among women with stage IV disease, there was no OS difference between PDS and NAC cohorts (median OS, 31.2 [30.4-32.3] vs 28.4 [27.2-30.2] months; hazard ratio [95% confidence interval], 0.93 [0.85-1.02]; P = 0.12)., Conclusions: Primary debulking surgery was associated with increased OS among women with stage III but not stage IV ovarian cancer in a nationally representative cohort with low NAC use. If this finding reflects treatment assignment bias, it suggests that providers often well select candidates for PDS rather than NAC, although median OS times remain low.

Objective: To determine overall survival (OS) and factors associated with OS after pelvic exenteration for cervical cancer., Methods: Women with cervical cancer who underwent exenteration (n = 517) were identified from the 1998 to 2011 National Cancer Database. Kaplan-Meier and multivariate Cox proportional-hazards survival analyses were performed to test for associations of potential explanatory variables with OS. Analyzed confounders included age, insurance status, income, distance from home to treatment center, stage, exenteration type, surgical margin status, and treatment with adjuvant radiation and/or chemotherapy., Results: Among the entire cohort with clinical follow-up (n = 313), median OS was 24 months. Stage (P = 2.5 × 10), lymph node status (P = 1.3 × 10), insurance status (P = 1.5 × 10), and histologic type (P = 0.04) were significantly associated with OS by the log-rank test. Unadjusted median OS was 24.2 and 61.8 months for women with squamous and adenocarcinoma histologies, respectively. By multivariate Cox regression, age, insurance status, stage, margin status, and adjuvant radiation were associated with OS. Histology was not independently associated with OS on multivariate regression. Among women with node-negative disease, median OS was 73.2 months., Conclusions: Exenteration may be curative for more than half of women with node-negative cervical cancer. Stage, insurance status, lymph node status, and surgical margin are independently associated with differential OS after exenteration.