OBJECTIVE Endocuff Vision (ECV) is the second generation of a device designed to improve polyp detection. The aim of this study was to evaluate its impact on adenoma detection rate (ADR) in routine colonoscopy. DESIGN This cluster-randomised crossover trial compared Endocuff-assisted (ECV+) with standard (ECV-) colonoscopy. Two teams of 11 endoscopists each with prior ECV experience, balanced in terms of basal ADR, gender and case volume were compared. In randomised fashion, the teams started with ECV+ or ECV- and switched group after inclusion of half of the cases. The main outcome criterion was ADR difference between ECV+ and ECV-. Subgroup analysis was done for physicians with low and high ADR ( less then or ≥ 25%). RESULTS During two periods of 20 and 21 weeks, respectively, the 22 endoscopists included 2058 patients (1032 ECV- vs 1026 ECV+, both groups being comparable). Overall ADR for both groups taken together was higher with ECV (39.2%) than without (29.4%; p less then 0.001) irrespective of the sequence of use (ECV+ or ECV- first), but mostly in adenomas less then 1 cm. In the physician subgroup analysis, only high detectors showed a significant ADR increase (from 31% to 41%, p less then 0.001), while the increase in the low detectors was not significant (from 24% to 30%, p=0.11). ECV had a positive impact in all colonic locations, except for the rectum. No ECV- related complication was reported. CONCLUSION We observed a significant ADR difference of approximately 10% by the use of ECV. By subgroup analysis, this increase was significant only in physicians classified as high detectors. TRIAL REGISTRATION NUMBER ClinicalTrials.gov (NCT03344055). © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.Immune checkpoint blockade is arguably the most effective current cancer therapy approach; however, its efficacy is limited to patients with "hot" tumors, warranting an effective approach to transform "cold" tumors. Oncolytic viruses (especially properly armed ones) have positive effects on almost every aspect of the cancer-immunity cycle and can change the cancer-immune set point of a tumor. Here, we tested whether oncolytic vaccinia virus delivering tethered interleukin 12 (IL-12) could turn a "cold" tumor into a "hot" tumor while avoiding IL-12's systemic toxicity. Our data demonstrated that tethered IL-12 could be maintained in the tumor without treatment-induced toxic side effects. Moreover, the treatment facilitated tumor infiltration of more activated CD4+ and CD8+ T cells and less Tregs, granulocytic myeloid-derivedsuppressor cells, and exhausted CD8+ T cells, with increased interferon γ and decreased transforming growth factor β, cyclooxygenase-2, and vascular endothelial growth factor expression, leading to transformed, immunogenic tumors and improved survival. Combined with programmed cell death 1 blockade, vaccinia virus expressing tethered IL-12 cured all mice with late-stage colon cancer, suggesting immediate translatability to the clinic. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Checkpoint inhibitors (CPIs) are thought to be effective against cutaneous melanoma in part because of the large burden of somatic mutations (neoantigens) generated from exposure to ultraviolet radiation. However, rare melanoma subtypes arising from acral skin, mucosal surfaces, and the uveal tract are largely sun-shielded. Genomic studies show these sun-shielded melanomas have a paucity of neoantigens and unique biology; they are thought to be largely resistant to immunotherapy. It has not been definitively shown that CPI improves survival in metastatic sun-shielded melanoma. METHODS We reviewed a single institutional experience using antibodies against CTLA-4, PD-1 and/or PD-L1 to treat patients with metastatic melanoma. Primary tumor histology was categorized as cutaneous, unknown, acral, mucosal, or uveal. We studied demographic data, treatment characteristics, and overall survival (OS) after CPI. RESULTS We treated 428 patients with metastatic melanoma from 2007 to 2019. Primary tumors were cuocal therapy was frequently employed to control disease progression. While sun-shielded melanomas exhibit worse outcomes after CPI than cutaneous melanomas, with an aggressive multidisciplinary approach, 5-year survival is still possible for 25%-32% of these patients. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Given the steep learning curve for neuraxial and peripheral nerve blocks, utilization of general anesthesia may increase as new house staff begin their residency programs. We sought to determine whether "July effect" affects the utilization of neuraxial anesthesia, peripheral nerve blocks, and opioid prescribing for lower extremity total joint arthroplasties (TJA) in July compared with June in teaching and non-teaching hospitals. METHODS Neuraxial anesthesia, peripheral nerve block use, and opioid prescribing trends were assessed using the Premier database (2006-2016). Analyses were conducted separately for teaching and non-teaching hospitals. Differences in proportions were evaluated via χ2 test, while differences in opioid prescribing were analyzed via Wilcoxon rank-sum tests. RESULTS A total of 1 723 256 TJA procedures were identified.  https://www.selleckchem.com/  The overall proportion of neuraxial anesthesia use in teaching hospitals was 14.4% in both June and July (p=0.940). No significant changes in neuraxial use were seen in non-teaching hospitals (24.