The Warburg effect in tumour cells is associated with the upregulation of glycolysis to generate ATP, even under normoxic conditions and the presence of fully functioning mitochondria. However, scientific advances made over the past 15 years have reformed this perspective, demonstrating the importance of oxidative phosphorylation (OXPHOS) as well as glycolysis in malignant cells. The metabolic phenotypes in melanoma display heterogeneic dynamism (metabolic plasticity) between glycolysis and OXPHOS, conferring a survival advantage to adapt to harsh conditions and pathways of chemoresistance. Furthermore, the simultaneous upregulation of both OXPHOS and glycolysis (metabolic symbiosis) has been shown to be vital for melanoma progression. The tumour microenvironment (TME) has an essential supporting role in promoting progression, invasion and metastasis of melanoma.Mesenchymal stromal cells (MSCs) in the TME show a symbiotic relationship with melanoma, protecting tumour cells from apoptosis and conferring chemoresistance. With the significant role of OXPHOS in metabolic plasticity and symbiosis, our review outlines how mitochondrial transfer from MSCs to melanoma tumour cells plays a key role in melanoma progression and is the mechanism by which melanoma cells regain OXPHOS capacity even in the presence of mitochondrial mutations. The studies outlined in this review indicate that targeting mitochondrial trafficking is a potential novel therapeutic approach for this highly refractory disease.

Customized individually manufactured total knee arthroplasty (CIM-TKA) was developed to improve kinematic total knee arthroplasty (TKA) performance. Component placement accuracy may influence the success of CIM-TKA designs. We performed this study to compare radiographic component alignment and revision rates of a cruciate retaining (CR) CIM-TKA and a contemporary posterior stabilized TKA (PS-TKA). After obtaining Institutional Review Board approval, we identified 94 CR CIM-TKAs (76 patients) and 91 PS-TKAs (82 patients) performed between July 1, 2013 and December 31, 2014 with a minimum 2-year follow-up (mean 41.1 months, range 24–59 months). We performed a retrospective electronic medical record review to identify patient demographic characteristics and revision procedures performed. Postoperative plain radiographs were reviewed to assess component alignment including cruciate ligament imbalance, femoral overhang, and femoral notching. Demographic characteristics, component malalignment, and revision surgery rates were assessed using a student's t-test or two-tailed Fisher's exact test, with a p-value < 0.05 designating significance. Technical errors were more commonly identified with CR CIM-TKA (29.8 vs. 9.9%, p < 0.001), including higher rates of tibiofemoral instability (13.8 vs. 1.1%, p < 0.01), femoral notching (12.8 vs. 3.3%, p = 0.03), and patellofemoral malalignment (20.2 vs. 7.7%, p = 0.02). CR CIM-TKA had more frequent coronal plane malposition (26.6 vs. 9.9%, p < 0.01) or sagittal plane reconstruction > 3 degrees outside of an optimized range (20.2 vs. 9.9%, p = 0.06). Aseptic revisions occurred more frequently with the CR CIM-TKA design (9.6 vs. 3.3%, p = 0.13). Demographic characteristics were not significantly different between the treatment groups. CR CIM-TKA may improve kinematic performance for patients undergoing knee replacement surgery. However, our study observations suggest that careful attention to surgical technique is important for optimizing implant survivorship with the CR CIM-TKA design. Additional study is needed to determine whether higher revision rates identified during this study are related to patient selection, surgical technique, or implant design.

IntroductionThere is a huge variation in the depth and breadth of content taught regarding orthopaedic examinations. Undergraduate students are often confused by the variability in examination teaching, therefore increasing concerns for upcoming objectively structured clinical examinations (OSCEs). Doctors, despite being expected to teach, rarely receive formal preparation, with only a handful of institutions providing necessary training. The Clinical Orthopaedic Teaching programme for Students (COTS) was designed to equip medical students with the knowledge to perform orthopaedic examinations and to synergistically provide senior students with the necessary experience for the future teaching required of them.MethodsSix fortnightly sessions were delivered, each focusing on a specific joint examination. Student and tutor recruitment were voluntary. Pre-session and post-session multiple-choice questions (MCQs) were provided to students to assess improvement in knowledge. Anonymous feedback forms were provided to both students and tutors.ResultsFrom 61 student responses, 98.4% of students stated that COTS met the learning outcomes, with content relevant for their medical curriculum. 96.7% supported COTS’ near-peer teaching (NPT) style for OSCE preparation. Based on a five-point Likert scale, students displayed a mean improvement in confidence (1.7±1.2, p<0.001) and MCQ scores (1.3±1.2, p<0.001). All 10 tutors perceived an improvement of their teaching skills and confidence to teach (1.0±0.9, p=0.016).ConclusionCOTS shows that an NPT style can be used to effectively teach orthopaedic examinations, with benefits for students and tutors. With our aim to refine and upscale this programme, we publish our pilot study findings to encourage similar teaching programmes to be adopted at other universities.

inhibits acute myeloid leukaemia metabolic capacity by blocking mitochondrial transfer from mesenchymal stromal cells.