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Isolated patellofemoral arthritis is an increasingly recognized entity, and is usually associated with previous patellofemoral dysplasia or instability. Patellofemoral arthroplasty (PFA) has evolved significantly in recent years, both in terms of implant design and importantly in the understanding of appropriate patient selection. This review outlines the indications and investigations for PFA, provides a brief history of the development of contemporary implants, and presents the clinical outcomes for the prostheses most commonly used in the UK. In addition, it provides a detailed surgical technique for implantation of an onlay implant, with tips on how to optimize patellofemoral biomechanics and thus achieve a consistently good outcome.  相似文献   
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PurposeTo determine whether change in shoulder position between internal rotation (IR) and external rotation (ER) during magnetic resonance arthrography (MRA) affects previously defined capsular measurements and to determine the utility of rotation in the diagnosis of instability.MethodsA retrospective study was conducted of patients who received a shoulder MRA with humeral IR and ER views. Patients with an arthroscopically confirmed diagnosis of instability and those with clinically stable shoulders, no history of instability, and no MRA findings of instability were identified and compared. Humeral rotation, glenoid retroversion, humeral head subluxation, capsular length, and capsular area using axial sequences of IR and ER views were recorded. Analysis compared IR, ER, and Δ capsular measurements between groups using independent t tests and univariate and multivariate regression.ResultsThirty-one subjects who were diagnosed with instability were included, along with 28 control subjects. Capsular length, capsular area, and humeral subluxations were significantly greater with ER compared with IR views (P < .001, P < .001, P < .001). Patients with instability displayed greater ER capsular length (P = .0006) and ER capsular area (P = .005) relative to controls. Multivariate logistic regression identified age, weight, sex, ER capsular length, and retroversion to be significant predictors of instability. ER capsular length independently predicts instability with 86% sensitivity and 84% specificity. Interobserver reliability using the intraclass correlation coefficient was rated good or excellent on all measurements.ConclusionVariance in humeral rotation during shoulder MRA significantly affects capsular measurements. Rotational views increase the utility of capsular measurements when assessing for instability, particularly capsular length and capsular area. The implementation of ER positioning enhances the ability to examine capsular changes of the shoulder joint and can assist in the diagnosis of instability.Level of EvidenceIII, retrospective comparative study  相似文献   
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Venetoclax is a promising agent in the treatment of acute myeloid leukemia (AML), though its antileukemic activity is limited to combination therapies. Mcl-1 downregulation, Bim upregulation, and DNA damage have been identified as potential ways to enhance venetoclax activity. In this study, we combine venetoclax with the dual PI3K and histone deacetylase inhibitor CUDC-907, which can downregulate Mcl-1, upregulate Bim, and induce DNA damage, as well as downregulate c-Myc. We establish that CUDC-907 and venetoclax synergistically induce apoptosis in AML cell lines and primary AML patient samples ex vivo. CUDC-907 downregulates CHK1, Wee1, RRM1, and c-Myc, which were found to play a role in venetoclax-induced apoptosis. Interestingly, we find that venetoclax treatment enhances CUDC-907-induced DNA damage potentially through inhibition of DNA repair. In vivo results show that CUDC-907 enhances venetoclax efficacy in an AML cell line derived xenograft mouse model, supporting the development of CUDC-907 in combination with venetoclax for the treatment of AML.  相似文献   
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BackgroundQuinacrine plus a fluoropyrimidine has in vivo efficacy against metastatic colorectal cancer (mCRC). This phase 1b trial evaluated the combination of quinacrine plus capecitabine in patients with treatment-refractory mCRC.Patients and MethodsUsing a modified Simon accelerated titration design, adults with treatment-refractory mCRC were treated with capecitabine 1000 mg/m2 twice daily for 14/21-day cycle, and escalating doses of quinacrine 100 mg daily, 100 mg twice daily, and 200 mg twice daily for 21 days. The primary endpoint was identifying the maximum tolerated dose, determining tolerability and safety. In an expansion cohort, it was overall response rate and time to tumor progression (TTP).ResultsTen patients (median age of 60 years) were treated in phase 1b. The first 2 quinacrine dosing levels were well tolerated. Dose-limiting toxicities were seen in 3 patients treated with quinacrine 200 mg twice daily. Five additional patients tolerated quinacrine 100 mg twice daily without further dose-limiting toxicities, thus establishing the maximum tolerated dose. Seven additional expansion-cohort patients enrolled onto the study before quinacrine manufacturing ceased within the United States. Five patients experienced stable disease, 1 partial response, and 10 disease progression. Median TTP overall was 2.12 months and median overall survival 5.22 months for the 17 patients.ConclusionCapecitabine and quinacrine can be safely administered at the maximum tolerated dose of capecitabine 1000 mg/m2 by mouth twice daily on days 1-14 and quinacrine 100 mg by mouth twice daily on days 1-21 of a 21-day cycle in mCRC patients. Although the expansion study was halted early, TTP was in line with other studies of refractory mCRC, suggesting activity of this regimen in heavily pretreated patients.  相似文献   
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Many airports are surfaced with grooved Marshall-designed dense graded asphalt. Grooving is required to satisfy regulatory aircraft skid resistance requirements, but introduces the risk of groove-related distress, such as groove closure. Consequently, airports seek an ungrooved runway surface option that performs similarly to dense graded asphalt but allows grooving to be avoided. Stone mastic asphalt is the most viable ungrooved runway surface solution and has been used on runways in Europe and China. However, before being accepted as an ungrooved runway surface in Australia, stone mastic asphalt must be shown to meet regulatory runway aircraft skid resistance requirements, and to otherwise perform similarly to typical dense graded asphalt mixtures for runway surfacing, including deformation resistance, fatigue cracking resistance and durability. Based on laboratory performance-related testing, 10-mm and 14-mm sized stone mastic asphalt mixtures, produced with four different aggregate sources, were found to generally meet the airport asphalt performance requirements. The 14 mm mixture was found to perform better than the 10 mm mixture, particularly regarding surface macrotexture and deformation resistance. It was concluded that airports should consider 14 mm sized stone mastic asphalt as an ungrooved runway surface in the future.  相似文献   
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