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Nuclear receptors (NRs) are implicated in the regulation of tumors and immune cells. We identify a tumor-intrinsic function of the orphan NR, NR2F6, regulating antitumor immunity. NR2F6 was selected from 48 candidate NRs based on an expression pattern in melanoma patient specimens (i.e., IFN-γ signature) associated with positive responses to immunotherapy and favorable patient outcomes. Correspondingly, genetic ablation of NR2F6 in a mouse melanoma model conferred a more effective response to PD-1 therapy. NR2F6 loss in B16F10 and YUMM1.7 melanoma cells attenuated tumor development in immune-competent but not -incompetent mice via the increased abundance of effector and progenitor-exhausted CD8 + T cells. Inhibition of NACC1 and FKBP10, identified as NR2F6 effectors, phenocopied NR2F6 loss. Inoculation of NR2F6 KO mice with NR2F6 KD melanoma cells further decreased tumor growth compared with NR2F6 WT mice. Tumor-intrinsic NR2F6 function complements its tumor-extrinsic role and justifies the development of effective anticancer therapies.

<p><strong><span lang="EN-IN">Background: </span></strong><span lang="EN-IN">Intra-articular calcaneus fracture is relatively rare and morbidity correlates with displacement and relative alignment of fragments. The treatment should address both components to maintain mechanics of foot. Among the available options open reduction and internal fixation is associated with major soft tissue complications and wound healing problems. As an alternative percutaneous fixation offer fewer complications yet good results for less severe calcaneus fractures. Our study aimed to contribute paucity of data available for these rare fractures and help to propose a preferred method of treatment.</span></p><p class="abstract"><strong>Methods:</strong> A hospital based study carried out on 20 patients over period of 2 year with closed displaced intra-articular tongue type of calcaneal fracture treated with percutaneous fixation and outcome was evaluated using clinical, radiological criteria and American Orthopaedic Foot &amp; Ankle Society (AOFAS) score. All patients were followed up for minimum 9 months with mean follow up of 13.5 month.<strong></strong></p><p class="abstract"><strong>Results:</strong> All patients had evidence of union within 2 month follow up. Mean correction in Bohler angle and Gissane angle was 23.2° and 25.4° respectively at final follow up. Mean change in heel height was 3.15 mm and width change was 2.75 mm compare to opposite side. Mean eversion inversion arch was 28° and near normal ankle range of motion. Functional outcome calculated on bases of AOFAS score revealed 18 patients (90%) had good results and 2 patients (10%) had fair results. Mean AOFAS score was 81.25. Complications were reported in three patients, one had signs of peroneal tendinitis and two had persistent pain and heel widening<span lang="EN-IN">. </span></p><p class="abstract"><strong>Conclusions: </strong>We believe percutaneous fixation should be considered as a preferred method for mild to moderately displaced tongue type of intraarticular calcaneus fractures. It potentially allows anatomical fracture reduction with lesser complications and good functional outcome<span lang="EN-IN">.</span></p>

Background: Proximal third femur fractures are common fractures seen in community. Till date large numbers of intramedullary and extramedullary implant were used in the treatment of these fractures. These fractures differ significantly from femoral shaft fractures and more proximal femoral fractures in mechanisms, treatment and complications. In 1996 AO group has introduced proximal femoral nail (PFN) for treatment of these fractures. The use of PFN in both these fractures resulted in rotational stability along with union in more anatomic position. Aims & Objective: To prove the advantages of PFN like (1) close reduction of fracture which decreases the blood loss and chance of infection; (2) controlled impaction of the fracture; (3) rotational stability; and (4) load bearing capacity of the implant. Material and Methods: We have done a retrospective study of proximal femur fractures operated with proximal femoral nailing at our institute with follow up of 5-36 months. Our study included 30 patients with 8 patients having intertrochanteric fracture and 22 patients having subtrochanteric fracture. Patient was asked to come for follow up on 1, 2, 3 and 6 months from the date of surgery. At each follow up patient was assessed clinically as per Harris Hip score12 and x ray AP/LAT view of hip with femur is taken. Results: It concludes that according to Boyd and Griffith classification type II is the most common variety. In our study excellent to good results noted in 74% patients. All of them performing their routine normal activity well. 5 patients had poor results. Complication rate in our study was much lower. There was only one infection which was known case of diabetes mellitus. Conclusion: The procedure takes less time and the patient can be mobilized fast postoperatively as well after fixation with PFN. PFN should always be considered for management of subtrochanteric fractures in young as well as elderly patients who have multiple pre-existing illnesses. PFN is a closed nailing procedure which achieves a Biological Fracture fixation with minimal blood loss, preserving the fracture hematoma and helping easy healing of the unstable subtrochanteric femoral fracture as well as intertrochanteric fracture.