Glucagon-like peptide-1 receptor agonists as a disease-modifying therapy for knee osteoarthritis mediated by weight loss: findings from the Shanghai Osteoarthritis Cohort.

OBJECTIVE: Obesity is a risk factor for knee osteoarthritis (KOA) development and progression. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are indicated for type 2 diabetes mellitus (T2DM) and obesity. However, whether KOA patients can benefit from GLP-1RA therapies has not been sufficiently investigated, especially in the long term. METHODS: The Shanghai Osteoarthritis Cohort study is a prospective, observational, multicentre study of >40 000 adults with clinically diagnosed osteoarthritis aged >45 years in Shanghai. We identified all KOA participants with comorbid T2DM enrolled from 1 January 2011 to 1 January 2017. Primary outcome was incidence of knee surgery after enrolment. Secondary outcomes included pain-relieving medication use, number of intra-articular therapies, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and medial femorotibial joint cartilage thickness. To evaluate the effects of GLP-1RA, we performed before-and-after comparison and comparison with participants who had no GLP-1RA exposure. RESULTS: For an intergroup comparison (non-GLP-1RA vs GLP-1RA), more weight loss (adjusted mean difference in weight change from baseline -7.29 kg (95% CI -8.07 to -6.50 kg), p<0.001) and lower incidence of knee surgery (93/1574 (5.9%) vs 4/233 (1.7%), adjusted p=0.014) were observed in the GLP-1RA group. Statistically significant differences in mean change from baseline for the WOMAC total and pain subscale scores were observed (adjusted mean difference in WOMAC total score -1.46 (95% CI -2.84 to -0.08), p=0.038; adjusted mean difference in WOMAC pain subscore -3.37 (95% CI -5.79 to -0.94), p=0.007). Cartilage-loss velocity of the medial femorotibial joint was significantly lower in the GLP-1RA group postadjustment for baseline characteristics (adjusted mean difference -0.02 mm (95% CI -0.03 to -0.002 mm), p=0.004). For the before-and-after comparison within the GLP-1RA group, we observed a significant decrease of symptom-relieving medication consumption and cartilage loss velocity of medial femorotibial joint (after-treatment vs before-treatment: -0.03±0.05 vs -0.05±0.07 mm/year, p<0.001). The association between GLP-1RA exposure and decreased incidence of knee surgery was mediated by weight reduction (mediation proportion: 32.1%), instead of glycaemic control (too small to calculate). CONCLUSION: With sufficient treatment duration, GLP-1RA therapies might be disease-modifying for KOA patients with comorbid T2DM, possibly mediated by weight loss. Further investigation is needed to elucidate effects of GLP-1RA on disease process, joint structure and patient-reported outcomes of osteoarthritis.

A scoping review of how early-stage knee osteoarthritis has been defined.

BACKGROUND: Early-stage knee osteoarthritis (KOA) classification criteria will enable consistent identification and trial recruitment of individuals with knee osteoarthritis (OA) at an earlier stage of the disease when interventions may be more effective. Toward this goal, we identified how early-stage KOA has been defined in the literature. METHODS: We performed a scoping literature review in PubMed, EMBASE, Cochrane, and Web of Science, including human studies where early-stage KOA was included as a study population or outcome. Extracted data included demographics, symptoms/history, examination, laboratory, imaging, performance-based measures, gross inspection/histopathologic domains, and the components of composite early-stage KOA definitions. RESULTS: Of 6142 articles identified, 211 were included in data synthesis. An early-stage KOA definition was used for study inclusion in 194 studies, to define study outcomes in 11 studies, and in the context of new criteria development or validation in six studies. The element most often used to define early-stage KOA was Kellgren-Lawrence (KL) grade (151 studies, 72%), followed by symptoms (118 studies, 56%), and demographic characteristics (73 studies, 35%); 14 studies (6%) used previously developed early-stage KOA composite criteria. Among studies defining early-stage KOA radiographically, 52 studies defined early-stage KOA by KL grade alone; of these 52, 44 (85%) studies included individuals with KL grade 2 or higher in their definitions. CONCLUSION: Early-stage KOA is variably defined in the published literature. Most studies included KL grades of 2 or higher within their definitions, which reflects established or later-stage OA. These findings underscore the need to develop and validate classification criteria for early-stage KOA.

A machine learning approach reveals features related to clinicians' diagnosis of clinically relevant knee osteoarthritis.

OBJECTIVES: To identify highly ranked features related to clinicians' diagnosis of clinically relevant knee OA. METHODS: General practitioners (GPs) and secondary care physicians (SPs) were recruited to evaluate 5-10 years follow-up clinical and radiographic data of knees from the CHECK cohort for the presence of clinically relevant OA. GPs and SPs were gathered in pairs; each pair consisted of one GP and one SP, and the paired clinicians independently evaluated the same subset of knees. A diagnosis was made for each knee by the GP and SP before and after viewing radiographic data. Nested 5-fold cross-validation enhanced random forest models were built to identify the top 10 features related to the diagnosis. RESULTS: Seventeen clinician pairs evaluated 1106 knees with 139 clinical and 36 radiographic features. GPs diagnosed clinically relevant OA in 42% and 43% knees, before and after viewing radiographic data, respectively. SPs diagnosed in 43% and 51% knees, respectively. Models containing top 10 features had good performance for explaining clinicians' diagnosis with area under the curve ranging from 0.76-0.83. Before viewing radiographic data, quantitative symptomatic features (i.e. WOMAC scores) were the most important ones related to the diagnosis of both GPs and SPs; after viewing radiographic data, radiographic features appeared in the top lists for both, but seemed to be more important for SPs than GPs. CONCLUSIONS: Random forest models presented good performance in explaining clinicians' diagnosis, which helped to reveal typical features of patients recognized as clinically relevant knee OA by clinicians from two different care settings.

Tips and Tricks in surgical reduction of the posterior column of AO/OTA C3 pilon fractures.

BACKGROUND: Accurate posterior column reduction remains a challenging and controversial topic in the management of complex pilon fractures (AO/OTA C3). We aim to report the outcomes of surgical treatment for 22 AO/OTA C3 pilon fracture cases between January 2015 and May 2017 and highlight some traps and tips. METHODS: Three patients underwent two-stage early plating on the posterior column through a posterolateral approach. The remaining 19 patients were treated with two-stage delayed plating on the posterior column: 11 patients were treated with a posterolateral approach, five patients with a modified posteromedial approach, and three patients with a single anterior approach. The reduction of the posterior column was evaluated according to the Burwell-Charnley's radiographic criteria, and functional outcomes were assessed using the American Orthopedic Foot and Ankle Society (AOFAS) scores. RESULTS: Posterior column malreduction occurred in five cases, including in one case that was re-adjusted immediately and in another case that was re-adjusted during a two-staged delayed operation. According to Burwell-Charnley's criteria, the satisfactory rate of fracture reduction was 81.8%. After 1 year, the mean AOFAS score was 81.9 (81.9 ± 9.9); the outcome was excellent in three (20.0%), good in nine (60.0%), and fair in three (20.0%). Excellent or good outcomes were noted in 12 patients (80.0%). CONCLUSIONS: The combined anterior and posterior approach is suggested in the second stage of plating so that the posterior column fragments can be re-adjusted intraoperatively, if necessary. Following these procedures, satisfactory reduction and recovery of good ankle function can be anticipated.

Cancellous bone allograft is comparable to fibular strut allograft for augmentation in three- or four-part proximal humeral fractures.

BACKGROUND: Bone grafts have been used for augmentation and improving stability of reduced fractures in proximal humeral fractures. The aim of this study was to analyze the clinical and radiological outcomes after the use of cancellous bone allografts (CAs) for augmentation in 3- or 4-part proximal humeral fractures, and compare with fibular strut allografts (FAs). METHODS: Between November 2016 and February 2018, 55 patients, followed for at least 1 year, with 3- or 4-part proximal humeral fractures fixed with locking plates were included and grouped according to the type of allograft bone used for augmentation. In this retrospective analysis, we assessed and compared the clinical and radiological outcomes of the 2 groups, using the visual analog scale score, the Constant-Murley score (CMS), the disability of the arm, shoulder, and hand (DASH) score, the range of movement, neck-shaft angle (NSA), humeral head height (HHH), and the changes of NSA and HHH, as well as recording any complications. The repeatedly measured clinical and radiological outcomes were analyzed by linear mixed models. The differences in outcomes between groups at the final follow-up were compared using Student's t test. RESULTS: There were 28 patients in the CA group and 27 patients in the FA group with an average follow-up of 14.5 months. The mean age of all patients was 64 (36-86). Nonsignificant group effects were observed on CMS (ß = -8.792, P = .216), DASH (ß = 1.329, P = .094), NSA (ß = 1.432, P = .752), and HHH (ß = 1.660, P = .628). At the final follow-up, the patients in the CA group showed no significant differences in visual analog scale (1.8 vs. 2.2, P = .276), CMS (81.5 vs. 75.4, P = .072), and DASH (11.0 vs. 13.5, P = .235) scores compared with the FA group. There were no significant differences in the change of NSA (6 vs. 4, P = .387) or HHH (1 vs. 2, P = .261). CONCLUSIONS: Patients with 3- or 4-part proximal humeral fractures treated with locking plates combined with CAs have good clinical and radiographic outcomes, similar to those treated with FAs.

Optimal viewing angles of intraoperative fluoroscopy for detecting screw penetration in proximal humeral fractures: a cadaveric study.

BACKGROUND: To identify the optimal viewing angles for every proximal screw in PHILOS plate-fixed proximal humeral fractures. METHODS: Three fresh-frozen human cadaveric bodies with six intact shoulders were studied. All three bodies were put in the beach chair position and PHILOS plates were placed on the proximal humerus. Head screws penetrating 1 mm into the joint were fitted one by one. Fluoroscopy was conducted in the 180° horizontal plane and the 120° coronal plane to analyze each screw's penetration in every shoulder. Images were taken every 5°, then all images were analyzed to identify the sensitive angles. RESULTS: The range of optimal viewing angles to visualize penetration of every head screw was identified. In the coronal plane, the angles in the range between 0° and 10° were sensitive to all screws except No. 8 and No. 9. Furthermore, penetration of screws No. 8 and 9 could not be identified on any axillary view, but could be identified in the horizontal plane from - 30° to - 10° and from 10° to 35° respectively. CONCLUSIONS: We recommend a 0°-10° axillary view with 30° arm abduction combined with two horizontal angles in the range of - 30° to - 10° and 10° to 35° for routine fluoroscopy during surgery. Our results will be helpful in avoiding primary screw penetration.

Production of Composite Scaffold Containing Silk Fibroin, Chitosan, and Gelatin for 3D Cell Culture and Bone Tissue Regeneration.

BACKGROUND Bone tissue engineering, a powerful tool to treat bone defects, is highly dependent on use of scaffolds. Both silk fibroin (SF) and chitosan (Cs) are biocompatible and actively studied for reconstruction of tissue engineering. Gelatin (Gel) is also widely applied in the biomedical field due to its low antigenicity and physicochemical stability. MATERIAL AND METHODS In this study, 4 different types of scaffolds were constructed - SF, SF/Cs, SF/Gel, and SF/Cs/Gel - and we compared their physical and chemical properties as well as biological characterization of these scaffolds to determine the most suitable scaffold for use in bone regeneration. First, these scaffolds were produced via chemical cross-linking method and freeze-drying technique. Next, the characterization of internal structure was studied using scanning electron microscopy and the porosity was evaluated by liquid displacement method. Then, we compared physicochemical properties such as water absorption rate and degradation property. Finally, MC3T3-E1 cells were inoculated on the scaffolds to study the biocompatibility and osteogenesis of the three-dimensional (3D) scaffolds in vitro. RESULTS The composite scaffold formed by all 3 components was the best for use in bone regeneration. CONCLUSIONS We conclude that the best scaffold among the 4 studied for MC3T3-E1 cells is our SF/Cs/Gel scaffold, suggesting a new choice for bone regeneration that can be used to treat bone defects or fractures in clinical practice.

Drug-inducible synergistic gene silencing with multiple small hairpin RNA molecules for gene function study in animal model.

Gene targeting is a critical tool for construction of disease models. However, the application of traditional homologous recombination-mediated gene knockout technology is limited by the absence of rapid frequency-guaranteed targeting methods. Although conventional small hairpin RNA (shRNA)-mediated gene silencing offers an alternative for gene targeting, its application is frequently compromised by lower expression efficiency via RNA interference compared to gene knockout. Here we provide an efficient gene targeting strategy involving drug-inducible synergistic silencing with multiple shRNA molecules. On induction, the levels of the target proteins decreased to undetectable levels in all the tested stable transgenic mammalian cell lines, including HEK293 and embryonic stem cell-derived progenies carrying shRNA silencing cassettes. In a transgenic mouse model carrying a silencing cassette targeting the rhodopsin gene, short-time inducer treatment was sufficient to ablate the rhodopsin protein in the retina, resulting in similar retinal phenotypic changes as those observed in rhodopsin mutant mice. Therefore, on a broad basis, this inducible shRNA gene targeting strategy offers a true gene knockout alternative comparable to conventional RNA interference approaches.

Evaluation of the Diagnostic Performance of American College of Rheumatology, EULAR, and National Institute for Health and Clinical Excellence Criteria Against Clinically Relevant Knee Osteoarthritis: Data From the CHECK Cohort.

OBJECTIVE: Our objective was to evaluate the diagnostic performance of the EULAR, American College of Rheumatology (ACR), and National Institute for Health and Care Excellence (NICE) criteria by using clinical experts' diagnosis of clinically relevant knee osteoarthritis (OA) as the outcome of interest. METHODS: In a previous study, we recruited clinical experts to evaluate longitudinal (5-, 8-, and 10-year follow-up) clinical and radiographic data of symptomatic knees from the Cohort Hip and Cohort Knee (CHECK) study for the presence or absence of clinically relevant OA. In the current study, ACR, EULAR, and NICE criteria were applied to the same 5-, 8-, and 10-year follow-up data; then a knee was diagnosed with OA if fulfilling the criteria at one of the three time points (F1), two of the time points (F2), or at all three time points (F3). Using clinically relevant OA as the reference standard, the sensitivity, specificity, and positive and negative predictive values for the three criteria were assessed. RESULTS: A total of 539 participants for a total of 833 examined knees were included. Thirty-six percent of knees were diagnosed with clinically relevant OA by experts. Sixty-seven percent to 74% of the knees received the same diagnosis (OA or non-OA) by the three criteria sets for the different definitions (F1 to F3). EULAR consistently (F1 through F3) had the highest specificity, and NICE consistently had the highest sensitivity. CONCLUSION: The diagnoses only moderately overlapped among the three criteria sets. The EULAR criteria seemed to be more suitable for study enrollment (when aimed at recruiting clinically relevant OA knees), given the highest specificities. The NICE criteria, given the highest sensitivities, could be more useful for an initial diagnosis in clinical practice.

TUBA1A licenses APC/C-mediated mitotic progression to drive glioblastoma growth by inhibiting PLK3.

Glioblastoma (GBM) is the most common, aggressive, and chemorefractory primary brain tumor in adults. Identifying novel drug targets is crucial for GBM treatment. Here, we demonstrate that tubulin alpha 1a (TUBA1A) is significantly upregulated in GBM compared to low-grade gliomas (LGG) and normal tissues. High TUBA1A expression is associated with poor survival in GBM patients. TUBA1A knockdown results in mitotic arrest and reduces tumor growth in mice. TUBA1A interacts with the polo-like kinase 3 (PLK3) in the cytoplasm to inhibit its activation. This interaction licenses activation of the anaphase-promoting complex or cyclosome (APC/C) to ensure proper Foxm1-mediated metaphase-to-anaphase transition and mitotic exit. Overall, our findings demonstrate that targeting TUBA1A attenuates GBM cell growth by suppressing mitotic progression in a PLK3-dependent manner.

Allografts are not necessary for displaced proximal humeral fractures in patients less than 65 years old, a retrospective cohort study.

INTRODUCTION: Displaced proximal humeral fractures (PHF) are frequently treated with locking plates to achieve osteosynthesis. Bone grafts are used as augmentation techniques to improve stability in osteoporotic patients. However, there has been little research into whether bone grafts are necessary for patients younger than 65 years old. This study compared radiographic and clinical outcomes between PHFs augmented with bone grafts or not in a younger population. METHODS: Between January 2016 and June 2020, 91 patients treated with a locking plate alone (LP), and 101 patients treated with locking plates augmented with bone grafts (BG) were analyzed. Potential confounding factors for outcomes were adjusted by propensity score-matching analyses. For the retrospective cohort study, 62 patients from each group were evaluated for radiographic outcomes and clinical outcomes and compared. RESULTS: Sixth-two patients in each group, both with a mean age of 52 years old, were with a mean follow-up time of 25 months in the LP group and 26 months in the BG group. There was no difference in demographic or surgical characteristics between the two groups after propensity score-matching. With regard to radiographic outcomes, the changes in neck-shaft angle (-5.1 ± 4.9 vs. -3.1 ± 5.3, p = 0.015) and humeral head height (-1.5 ± 2.5 vs. -0.4 ± 2.7, p = 0.002) were more obvious in the BG group. However, regarding functional outcomes, there were no significant differences between the two groups in DASH score, Constant-Murley score, or VAS score. Moreover, the complication rate was not significantly different between two groups. DISCUSSION: Allografts only provide minor improvements of stability in radiography for patients less than 65 years old after locking plate fixation of PHFs, but don't improve shoulder function, relieve pain or reduce complications. We concluded that allografts are unnecessary for younger patients with displaced PHFs.

Nonanatomic healing of the greater tuberosity after plating in proximal humeral fractures: a case control study.

BACKGROUND: Open reduction and plate internal fixation (ORIF) is one of the most common treatment methods for proximal humeral fractures. Complications associated with the greater tuberosity (GT) are rarely reported, therefore, the purpose of this study was to analyze the complications associated with the GT and the risk factors after locked-plate internal fixation. METHODS: We retrospectively analyzed the medical and radiographic data of patients with proximal humeral fractures involving the GT treated with locking plates between January 2016 and July 2019. We divided all patients into two groups, the anatomic GT healing group and the nonanatomic GT healing group, depending on the radiographic outcomes of the GT. Clinical outcome was assessed by the Constant scoring system. Potential risk factors included preoperative and intraoperative factors. Preoperative factors included sex, age, body mass index, fracture type, fracture-dislocation, proximal humeral bone mineral density, humeral head extension, hinge integrity, comminuted GT, volume and surface area of the main GT fragment, and displacement of the main GT fragment. Intraoperative factors were adequate medial support, residual head-shaft displacement, head-shaft angle and residual GT displacement. Univariate logistic regression and multivariate logistic regression were used to identify risk factors. RESULTS: There were 207 patients (130 women and 77 men; mean age, 55 years). GT anatomic healing was observed in 139 (67.1%) patients and nonanatomic healing in 68 (32.9%). Patients with GT nonanatomic healing had significantly inferior Constant scores than those with GT anatomic healing (75.0 ± 13.9 vs. 83.9 ± 11.8, P < 0.001). Patients with high GT malposition had worse Constant scores than patients with low GT malposition (73.3 ± 12.7 vs. 81.1 ± 11.4, P = 0.039). The multivariate logistic model showed that GT fracture characteristics were not risk factors for nonanatomic GT healing, while residual GT displacement was. CONCLUSIONS: Nonanatomic healing of the GT is a high-rate complication of proximal humeral fractures, resulting in inferior clinical outcomes, especially for high GT malposition. Fracture characteristics of the GT are not risk factors for GT nonanatomic healing and GT comminution should not be regarded as a contraindication to ORIF for proximal humeral fractures.

Effect of Fibular Allograft Augmentation in Medial Column Comminuted Proximal Humeral Fractures: A Randomized Controlled Trial.

BACKGROUND: Previous observational studies and meta-analyses have recommended augmentation with a fibular allograft (FA) during the treatment of proximal humeral fractures with locking plates (LPs). However, to our knowledge, randomized controlled trials comparing open reduction and internal fixation (ORIF) with and without FA have not been performed to date. METHODS: This was a randomized controlled trial in which adults with a medial column comminuted proximal humeral fracture were randomly allocated to undergo ORIF with an LP (the LP group) or with an LP augmented with an FA (the FA group). Patients were followed for 24 months. The primary outcome was the Disabilities of the Arm, Shoulder and Hand (DASH) score at 12 months after the surgical procedure. The secondary outcomes included the DASH score at other time points, shoulder function, pain score, satisfaction, complications, and changes in neck-shaft angle and humeral head height. RESULTS: From October 20, 2016, to December 24, 2019, 80 patients were randomized. There were 52 women (65%), and the mean patient age (and standard deviation) was 65 ± 14 years. Of the 80 patients, 39 were allocated to the FA group and 41 were allocated to the LP group. At the primary time point (12 months), the unadjusted mean between-group difference in DASH score was -1.2 (95% confidence interval [CI], -7.3 to 5.0; p = 0.71) favoring the FA group, and, with adjustment for smoking, alcohol drinking, and diabetes, the between-group difference was -1.4 (95% CI, -7.7 to 5.0; p = 0.67) favoring FA. No significant differences between the 2 groups were found among the secondary outcomes. CONCLUSIONS: No additional benefit was found for FA augmentation in treating medial column comminuted proximal humeral fractures. LEVEL OF EVIDENCE: Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence.

Diagnosis for early stage knee osteoarthritis: probability stratification, internal and external validation; data from the CHECK and OAI cohorts.

OBJECTIVE: To internally and externally validate our diagnostic criteria of early stage knee osteoarthritis (OA) in the CHECK and OAI cohorts. DESIGN: We applied two previously developed diagnostic models to all knees in CHECK and OAI cohorts to calculate probabilities of early stage knee OA at baseline. Knees were categorized into three groups based on probability: 'no OA' (probability ≤ 30%), 'uncertain' (probability between 30% and 70%) and 'early stage OA' (probability ≥ 70%). To validate the diagnosis, we obtained OA related outcome measures at 10-year follow-up in the CHECK cohort, and at 8-9-year follow-up in the OAI cohort. We compared outcome measures between 'no OA' and 'early stage OA' knees, and between 'no OA' and 'uncertain' knees using generalized estimating equations. RESULTS: In CHECK (n = 1042 knees) both models showed 'early stage OA' knees presented with significant and clinically relevant higher WOMAC scores, higher Kellgren & Lawrence (KL) grade, and higher rates of joint space narrowing (JSN) progression after 10 years, compared to 'no OA' knees. In OAI (n = 2937 knees) both models showed 'early stage OA' knees presented with significant and clinically relevant higher WOMAC scores, higher KL grade, and higher rates of KL and JSN progression after 8-9 years, compared to 'no OA' knees. Smaller, but still significant differences between 'uncertain' and 'no OA' knees were observed in both cohorts. CONCLUSIONS: These results support internal and external validity of the two sets of diagnostic criteria for early stage knee OA.

Effect of Intramuscular vs Intra-articular Glucocorticoid Injection on Pain Among Adults With Knee Osteoarthritis: The KIS Randomized Clinical Trial.

Importance: Intra-articular (IA) glucocorticoid injection is widely used in patients with knee osteoarthritis (OA), but the safety of this technique is in question among physicians. Intramuscular (IM) glucocorticoid injection could be an alternative approach. Objective: To investigate whether an IM glucocorticoid injection is noninferior to an IA glucocorticoid injection in reducing knee pain for patients with knee OA in primary care. Design, Setting, and Participants: The KIS trial, a multicenter, open-label, randomized clinical noninferiority trial including patients with symptomatic knee OA, was conducted in 80 primary care general practices in the southwest of the Netherlands. The study was conducted from March 1, 2018, to July 28, 2020. Interventions: Patients were randomly allocated to receive an injection of triamcinolone acetonide, 40 mg, either IM in the ipsilateral ventrogluteal region or IA in the knee joint. All patients were followed up for 24 weeks. Main Outcomes and Measures: The pain score at 4 weeks measured with Knee Injury and Osteoarthritis Outcome Score (range, 0-100; 0 indicates extreme pain), with a noninferiority margin of -7 (IM minus IA). A per-protocol analysis was prespecified as the primary analysis. Results: A total of 145 patients (94 women [65%]; mean [SD] age, 67 [10] years) were included; of these, 138 patients (IM, 72; IA, 66) were included in the per-protocol analysis. Clinically relevant improvements in knee pain were reached up to 12 weeks after the injection in both groups. At 4 weeks, the estimated mean difference in the Knee Injury and Osteoarthritis Outcome Score between the 2 groups was -3.4 (95% CI, -10.1 to 3.3). Noninferiority could not be declared because the lower limit exceeded the noninferiority margin. Intramuscular injection was noninferior to IA injection at 8 (mean difference, 0.7; 95% CI, -6.5 to 7.8) and 24 (mean difference, 1.6; 95% CI, -5.7 to 9.0) weeks. No significant difference was found among all the secondary outcomes. These results were similar for the sensitivity analysis in an intention-to-treat population. The most frequently reported adverse events were hot flush (IM, 7 [10%] vs IA, 14 [21%]) and headache (IM, 10 [14%] vs IA, 12 [18%]), and all events were classified as nonserious. Conclusions and Relevance: Based on the findings of this trial, among patients with knee OA in primary care, IM glucocorticoid injection could present an inferior effect in reducing pain at 4 weeks compared with IA injection. Noninferiority of an IM injection was observed at 8 and 24 weeks after injection. This trial provides data for shared decision-making, taking into account the advantages and disadvantages of both types of injections. Trial Registration: Dutch Trial Registry: NTR6968.

Diagnosis of early stage knee osteoarthritis based on early clinical course: data from the CHECK cohort.

BACKGROUND: Early diagnosis of knee osteoarthritis (OA) is important in managing this disease, but such an early diagnostic tool is still lacking in clinical practice. The purpose of this study was to develop diagnostic models for early stage knee OA based on the first 2-year clinical course after the patient's initial presentation in primary care and to identify whether these course factors had additive discriminative value over baseline factors. METHODS: We extracted eligible patients' clinical and radiographic data from the CHECK cohort and formed the first 2-year course factors according to the factors' changes over the 2 years. Clinical expert consensus-based diagnosis, which was made via evaluating patients' 5- to 10-year follow-up data, was used as the outcome factor. Four models were developed: model 1, included clinical course factors only; model 2, included clinical and radiographic course factors; model 3, clinical baseline factors + clinical course factors; and model 4, clinical and radiographic baseline factors + clinical and radiographic course factors. All the models were built by a generalized estimating equation with a backward selection method. Area under the receiver operating characteristic curve (AUC) and its 95% confidence interval (CI) were calculated for assessing model discrimination. Delong's method compared AUCs. RESULTS: Seven hundred sixty-one patients with 1185 symptomatic knees were included in this study. Thirty-seven percent knees were diagnosed as OA at follow-up. Model 1 contained 6 clinical course factors; model 2: 6 clinical and 3 radiographic course factors; model 3: 6 baseline clinical factors combined with 5 clinical course factors; and model 4: 4 clinical and 1 radiographic baseline factors combined with 5 clinical and 3 radiographic course factors. Model discriminations are as follows: model 1, AUC 0.70 (95% CI 0.67-0.74); model 2, 0.74 (95% CI 0.71-0.77); model 3, 0.77 (95% CI 0.74-0.80); and model 4, 0.80 (95% CI 0.77-0.82). AUCs of model 3 and model 4 were slightly but significantly higher than corresponding baseline-factor models (model 3 0.77 vs 0.75, p = 0.031; model 4 0.80 vs 0.76, p = 0.003). CONCLUSIONS: Four diagnostic models were developed with "fair" to "good" discriminations. First 2-year course factors had additive discriminative value over baseline factors.

The neck-shaft angle is the key factor for the positioning of calcar screw when treating proximal humeral fractures with a locking plate.

AIMS: The aim of this study was to explore why some calcar screws are malpositioned when a proximal humeral fracture is treated by internal fixation with a locking plate, and to identify risk factors for this phenomenon. Some suggestions can be made of ways to avoid this error. METHODS: We retrospectively identified all proximal humeral fractures treated in our institution between October 2016 and October 2018 using the hospital information system. The patients' medical and radiological data were collected, and we divided potential risk factors into two groups: preoperative factors and intraoperative factors. Preoperative factors included age, sex, height, weight, body mass index, proximal humeral bone mineral density, type of fracture, the condition of the medial hinge, and medial metaphyseal head extension. Intraoperative factors included the grade of surgeon, neck-shaft angle after reduction, humeral head height, restoration of medial support, and quality of reduction. Adjusted binary logistic regression and multivariate logistic regression models were used to identify pre- and intraoperative risk factors. Area under the curve (AUC) analysis was used to evaluate the discriminative ability of the multivariable model. RESULTS: Data from 203 patients (63 males and 140 females) with a mean age of 62 years (22 to 89) were analyzed. In 49 fractures, the calcar screw was considered to be malpositioned; in 154 it was in the optimal position. The rate of malpositioning was therefore 24% (49/203). No preoperative risk factor was found for malpositioning of the calcar screws. Only the neck-shaft angle was found to be related to the risk of screw malpositioning in a multivariate model (with an AUC of 0.72). For the fractures in which the neck-shaft angle was reduced to between 130° and 150°, 91% (133/46) of calcar screws were in the optimal position. CONCLUSION: The neck-shaft angle is the key factor for the appropriate positioning of calcar screws when treating a proximal humeral fracture with a locking plate. We recommend reducing the angle to between 130° and 150°. Cite this article: Bone Joint J 2020;102-B(12):1629-1635.

Locking Plate Combined With Endosteal Fibular Allograft Augmentation for Medial Column Comminuted Proximal Humeral Fracture.

The goal of this study was to evaluate the role of endosteal fibular allografts in the treatment of medial column comminuted proximal humerus fractures with a locking plate. The authors retrospectively analyzed the clinical outcomes of 63 patients (21 men and 42 women) who had proximal humerus fractures with a comminuted medial column and were treated at Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China, with a locking plate, either alone or in combination with a fibular strut allograft, between January 2013 and May 2017. Patients were divided into 2 groups: locking plate combined with fibular allograft (41 patients) and locking plate alone (22 patients). After an average follow-up of 16.3 months, all fractures were healed. Statistically significant differences were seen between the 2 groups in changes in the neck-shaft angle, humeral head height (P<.001), and overall incidence of complications (P<.05). However, no statistically significant difference was found in the Constant-Murley score. The use of a locking plate in combination with intramedullary fibular allograft augmentation can help to maintain reduction and reduce postoperative complications in the treatment of proximal humerus fractures that are complicated by medial column comminution. [Orthopedics. 2020;43(6):367-372.].