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Endoplasmic reticulum (ER) stress has been shown to promote chondrocyte apoptosis and osteoarthritis (OA) progression, but the precise mechanisms via which ER stress is modulated in OA remain unclear. Here we report that DEP domain‐containing mTOR‐interacting protein (DEPTOR) negatively regulated ER stress and OA development independent of mTOR signaling. DEPTOR is ubiquitinated in articular chondrocytes and its expression is markedly reduced along with OA progression. Deletion of DEPTOR in chondrocytes significantly promoted destabilized medial meniscus (DMM) surgery‐induced OA development, whereas intra‐articular injection of lentivirus‐expressing DEPTOR delayed OA progression in mice. Proteomics analysis revealed that DEPTOR interplayed with TRC8, which promoted TRC8 auto‐ubiquitination and degraded by the ubiquitin–proteasome system (UPS) in chondrocytes. Loss of DEPTOR led to TRC8 accumulation and excessive ER stress, with subsequent chondrocyte apoptosis and OA progression. Importantly, an inhibitor of ER stress eliminated chondrocyte DEPTOR deletion‐exacerbated OA in mice. Together, these findings establish a novel mechanism essential for OA pathogenesis, where decreasing DEPTOR in chondrocytes during OA progression relieves the auto‐ubiquitination of TRC8, resulting in TRC8 accumulation, excessive ER stress, and OA progression. Targeting this pathway has promising therapeutic potential for OA treatment. © 2020 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Background: Having a senior surgeon present for high-risk patients is an important safety measure in emergency surgery, but 24-h consultant cover is not efficient. We aimed to develop a user-friendly toolbox (risk identification, outcome prediction and patient stratification) to support when to involve a senior surgeon.Materials and Methods: We included 11,901 general surgery patients (10.0% emergencies) in a multicenter prospective cohort in China (2015-2016). Patient information and surgeons' seniority were compared between emergency and elective surgery with the same procedure codes. Risk indicators common in these two surgical timings and specific to emergency surgery were identified, and their clinical importance was evaluated by a working group of 48 experienced surgeons. Predictive models for mortality and morbidity were built using logistic regression models. Stratification rules were created to balance patients' risk and surgeons' caseload with an Acute Call Team (ACT) model.Results: Emergency patients had significantly higher risks of mortality (3.6% vs 0.6%) and morbidity (7.8% vs 4.3%) than elective patients, but disproportionally fewer senior surgeons (59.9% vs 91.4%) were present. Using three risk indicators (American Society of Anesthesiologists score, age, blood urea nitrogen), C-statistic (95% CI) for prediction of emergency mortality was high [0.90 (0.84-0.96)]. It was less complex but equally accurate as two existing and validated models (0.86 [0.79-0.93] and 0.86 [0.77-0.95]). Using five indicators, C-statistic (95% CI) was moderate for prediction of overall morbidity [0.77 (0.72-0.83)], but high for severe morbidity [0.92 (0.88-0.97)]. Based on stratification rules of the ACT model, patient mortality and morbidity were 0.5% and 5.3% in the low-risk stratum (composing 64.6% of emergency caseload), and 15.9% and 29.0% in the very high-risk stratum (6.9% of caseload).Conclusion: These findings show the practical feasibility of using a risk assessment tool to direct senior surgeons' involvement in emergency general surgery. [ABSTRACT FROM AUTHOR]

Objectives To examine trends in the initial prescription of commonly-prescribed analgesics and patient- as well as practice-level factors related to their selection in incident OA. Methods Patients consulting with incident clinical OA between 2000–2016 were identified within The Health Improvement Network in the United Kingdom (UK) general practice. Excluded were patients who had history of cancer or were prescribed the analgesics of interest within 6 months before diagnosis of OA. Initial analgesic prescription included oral non-selective NSAID, oral selective cyclooxygenase-2 inhibitor, topical NSAID, paracetamol, topical salicylate or oral/transdermal opioid within 1 month after OA diagnosis. Results ∼44% of patients with incident OA (n  = 125 696) were prescribed one of these analgesics. Incidence of oral NSAID prescriptions decreased whereas other analgesic prescriptions, including oral opioid prescriptions, increased (all P -for-trend < 0.001). Patients with a history of gastrointestinal disease were more likely to receive topical NSAIDs, paracetamol or oral/transdermal opioids. Only 38% of patients with history of gastrointestinal disease and 21% of patients without it had co-prescription of gastroprotective agent with oral NSAIDs. Oral/transdermal opioid prescription was higher among the elderly (≥65 years), women, obesity, current smoker, and patients with gastrointestinal, cardiovascular or chronic kidney disease. Prescription of oral opioids increased with social deprivation (P -for-trend < 0.05) and was highest in Scotland, whereas transdermal opioid prescription was highest in Northern Ireland (all P -for-homogeneity-test < 0.05). Conclusion The initial prescription pattern of analgesics for OA has changed over time in the UK. Co-prescription of gastroprotective agents with oral NSAIDs remains suboptimal, even among those with prior gastrointestinal disease. [ABSTRACT FROM AUTHOR]

Objectives: Osteoarthritis is a leading cause of immobility and joint replacement, two strong risk factors for venous thromboembolism (VTE). We aimed to examine the relation of knee, hip and hand osteoarthritis to the risk of VTE and investigate joint replacement as a potential mediator.Methods: We conducted three cohort studies using data from The Health Improvement Network. Up to five individuals without osteoarthritis were matched to each case of incident knee (n=20 696), hip (n=10 411) or hand (n=6329) osteoarthritis by age, sex, entry time and body mass index. We examined the relation of osteoarthritis to VTE (pulmonary embolism and deep vein thrombosis) using a multivariable Cox proportional hazard model.Results: VTE developed in 327 individuals with knee osteoarthritis and 951 individuals without osteoarthritis (2.7 vs 2.0 per 1000 person-years), with multivariable-adjusted HR being 1.38 (95% CI 1.23 to 1.56). The indirect effect (HR) of knee osteoarthritis on VTE through knee replacement was 1.07 (95% CI 1.01 to 1.15), explaining 24.8% of its total effect on VTE. Risk of VTE was higher in hip osteoarthritis than non-osteoarthritis (3.3 vs 1.8 per 1000 person-years; multivariable-adjusted HR=1.83, 95% CI 1.56 to 2.13). The indirect effect through hip replacement yielded an HR of 1.14 (95% CI 1.04 to 1.25), explaining 28.1% of the total effect. No statistically significant difference in VTE risk was observed between hand osteoarthritis and non-osteoarthritis (1.5 vs 1.6 per 1000 person-years; multivariable-adjusted HR=0.88, 95% CI 0.67 to 1.16).Conclusion: Our large population-based cohort study provides the first evidence that knee or hip osteoarthritis, but not hand osteoarthritis, was associated with an increased risk of VTE, and such an association was partially mediated through knee or hip replacement. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy and safety of individual devices for femoral and/or tibial graft fixation in anterior cruciate ligament (ACL) reconstruction.Methods: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to December 12, 2018. Randomized controlled trials comparing individual devices for ACL graft fixation were included. Bayesian network meta-analysis was performed to assess the efficacy profile using the following outcomes: Lysholm score, International Knee Documentation Committee (IKDC) category, laxity, range of motion, and Tegner score. The incidence of infection, effusion, and graft rupture for each device was reported.Results: We included 57 randomized controlled trials involving 4,304 patients aged 23.8 to 40.9 years. The female proportion ranged from 0% to 100%. The length of follow-up ranged from 6 to 144 months. Of the 13 studied femoral fixation devices, none was significantly different from the others regarding the Lysholm score, IKDC category, range of motion, and Tegner score. Bioabsorbable interference screws (standardized mean difference, 1.3; 95% credible interval, 0.0-2.5) showed higher laxity than the EndoPearl at a borderline level of statistical significance, but the difference varied substantially within multiple sensitivity analyses. Infection (2.0%) was most commonly seen with the EndoPearl, whereas the bone mulch screw had the highest incidence of effusion (5.5%) and graft rupture (5.5%). For the 9 studied tibial fixation devices, no significant difference was observed in the aforementioned efficacy measurements. Bioabsorbable interference screws with staples had the highest incidence of infection (11.1%) and effusion (15.6%), whereas graft rupture was most commonly seen with the bone plug (4.0%).Conclusions: Graft fixation devices in ACL reconstruction share a similar efficacy profile in terms of the Lysholm score, IKDC category, range of motion, and Tegner score but not laxity. On the other hand, safety profiles seem to vary among different devices. These findings can support surgeons, alongside their experience and preference, as well as the relative cost of each device, in delivering an individualized plan for an optimal operation.Level Of Evidence: Level II, meta-analysis of Level I and II studies. [ABSTRACT FROM AUTHOR]

Several professional organizations have recommended tramadol as one of the first‐line or second‐line therapies for patients with chronic noncancer pain and its prescription has been increasing rapidly worldwide; however, the safety profile of tramadol, such as risk of fracture, remains unclear. This study aimed to examine the association of tramadol with risk of hip fracture. Among individuals age 50 years or older without a history of hip fracture, cancer, or opioid use disorder in The Health Improvement Network (THIN) database in the United Kingdom general practice (2000–2017), five sequential propensity score–matched cohort studies were assembled, ie, participants who initiated tramadol or those who initiated one of the following medications: codeine (n = 146,956) (another commonly used weak opioid), naproxen (n = 115,109) or ibuprofen (n = 107,438) (commonly used nonselective nonsteroidal anti‐inflammatory drugs [NSAIDs]), celecoxib (n = 43,130), or etoricoxib (n = 27,689) (cyclooxygenase‐2 inhibitors). The outcome was incident hip fracture over 1 year. After propensity‐score matching, the included participants had a mean age of 65.7 years and 56.9% were women. During the 1‐year follow‐up, 518 hip fracture (3.7/1000 person‐years) occurred in the tramadol cohort and 401 (2.9/1000 person‐years) occurred in the codeine cohort. Compared with codeine, hazard ratio (HR) of hip fracture for tramadol was 1.28 (95% confidence interval [CI] 1.13 to 1.46). Risk of hip fracture was also higher in the tramadol cohort than in the naproxen (2.9/1000 person‐years for tramadol, 1.7/1000 person‐years for naproxen; HR = 1.69, 95% CI 1.41 to 2.03), ibuprofen (3.4/1000 person‐years for tramadol, 2.0/1000 person‐years for ibuprofen; HR = 1.65, 95% CI 1.39 to 1.96), celecoxib (3.4/1000 person‐years for tramadol, 1.8/1000 person‐years for celecoxib; HR = 1.85, 95% CI 1.40 to 2.44), or etoricoxib (2.9/1000 person‐years for tramadol, 1.5/1000 person‐years for etoricoxib; HR = 1.96, 95% CI 1.34 to 2.87) cohort. In this population‐based cohort study, the initiation of tramadol was associated with a higher risk of hip fracture than initiation of codeine and commonly used NSAIDs, suggesting a need to revisit several guidelines on tramadol use in clinical practice. © 2020 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Objective: The aim was to examine the association between dietary selenium intake and nonalcoholic fatty liver disease (NAFLD) in a large group of middle-aged and elderly Chinese persons.Method: The data included in this analysis were from a population-based study, the Xiangya Hospital Health Management Center Study. NAFLD was diagnosed by (1) imaging or histological evidence of hepatic steatosis; (2) absence of specific etiologies of NAFLD; and (3) no heavy consumption of alcohol. Dietary selenium intake was assessed using a validated semi-quantitative food frequency questionnaire. The association between dietary selenium intake and the prevalence of NAFLD was evaluated using logistic and spline regression in a cross-sectional study of 5436 subjects.Results: The prevalence of NAFLD was 36.8%. Compared with the lowest quintile, the energy-adjusted odds ratios for NAFLD were 1.27 (95% confidence interval [CI], 1.07-1.52), 1.30 (95% CI, 1.09-1.55), and 1.58 (95% CI, 1.33-1.89) for the third, fourth, and fifth quintiles of selenium intake, respectively, and there was a positive dose-response relationship (r = 0.88, p for trend = 0.008). Similar results were observed for men and women separately. The findings were not materially altered by adjustment for potential confounders (i.e., age, gender, body mass index, smoking status, diabetes, hypertension, activity level, nutritional supplements, energy intake, fat intake, fiber intake, cholesterol and saturated fatty acid intake).Conclusions: In this middle-aged and elderly population, subjects with higher dietary selenium intake, even below the recommended nutrient intake in China, had higher prevalence of NAFLD in a dose-response relationship manner. [ABSTRACT FROM AUTHOR]

• A fluorescence method was developed for comprehensive evaluation of CTCV. • PARAFAC completed the spectra characterization of CTCV. • The classification models were established by LDA, PLS-DA and N -PLS-DA. • The fluorescence components were strongly related to antioxidant activity of CTCV. • Antioxidant properties were accurately quantified through PSO-VWLS-SVM model. In this work, a rapid and accurate strategy for classification of Chinese traditional cereal vinegars (CTCV) and antioxidant property predication was proposed by using the combination fluorescence spectroscopy and machine learning. Three characteristic fluorescent components were extracted by parallel factor analysis (PARAFAC), which have correlations greater than 0.8 with antioxidant activity of CTCV obtained by Pearson correlation analysis. Machine learning methods, including linear discriminant analysis (LDA), partial least squares-discriminant analysis (PLS-DA) and N -way partial least squares discriminant analysis (N -PLS-DA), were used for the classification of different types of CTCV, and the correct classification rates was higher than 97%. The antioxidant property of CTCV were further quantified by using optimized variable-weighted least-squares support vector machine based on particle swarm optimization (PSO-VWLS-SVM). The proposed strategy provides a basis for further research on antioxidant active ingredients and antioxidant mechanisms of CTCV, and enable the continued exploration and application of CTCV from different types. [ABSTRACT FROM AUTHOR]

The authors responds to a commentary on a study which described nonsteroidal anti-inflammatory drug (NSAID)-aspirin interactions and the risk of cardiovascular disease (CVD) in patients with osteoarthritis. They agree with the need to confirm the concurrent-use status of low-dose aspirin and pain-relief medication in patients with osteoarthritis. They identify the hazard ratio for the association between initiation of naproxen versus other NSAIDs and CVID events in persons with CVD history.

National epidemiological data in China are absent for revision total knee arthroplasty (TKA). This study aimed to investigate the burden and characteristics of revision TKA in China. We reviewed 4,503 revision TKA cases registered in the Hospital Quality Monitoring System in China between 2013 and 2018 using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Revision burden was determined by the ratio of the number of revision procedures to the total number of TKA procedures. Demographic characteristics, hospital characteristics, and hospitalization charges were identified. The revision TKA cases accounted for 2.4% of all TKA cases. The revision burden showed an increasing trend from 2013 to 2018 (2.3% to 2.5%) (P for trend =.034). Gradual increases in revision TKA were observed in patients aged > 60 years. The most common causes for revision TKA were infection (33.0%) and mechanical failure (19.5%). More than 70% of the patients were hospitalized in provincial hospitals. A total of 17.6% patients were hospitalized in a hospital outside the province of their residence. The hospitalization charges continued to increase between 2013 and 2015 and remained roughly stable over the next three years. This study provided epidemiological data for revision TKA in China based on a national database. There was a growing trend of revision burden during the study period. The focalized nature of operations in a few higher volume regions was observed and many patients had to travel to obtain their revision procedure. [ABSTRACT FROM AUTHOR]