IntroductionCancer vaccination has been researched as a means of treating and preventing cancer, but successful translational efforts yielding clinical therapeutics have been limited. Numerous reasons have been offered in explanation, pertaining both to the vaccine formulation, and the clinical trial methodology used. This study aims to characterize the tumor vaccine clinical trial landscape quantitatively, and explore the possible validity of the offered explanations including the translational obstacles posed by the current common endpoints.MethodsWe performed a detailed cross-sectional and longitudinal analysis of tumor vaccine trials (n=955) registered in the US Clinical Trials database.ResultsThe number of tumor vaccine trials initiated per annum has declined 30% since a peak in 2008. In terms of vaccine formulation, 25% of trials use tumor cell/lysate preparations; whereas, 73% of trials vaccinate subjects against defined protein/peptide antigens. Also, 68% of trials do not use vectors for antigen delivery. Both these characteristics of tumor vaccines have remained unchanged since 1996. The top five types of cancer studied are: melanoma (22.6%); cervical cancer (13.0%); breast cancer (11.3%); lung cancer (9.5%); and prostate cancer (9.4%). In addition, 86% of the trials are performed where there is established disease rather than prophylactically, of which 67% are performed exclusively in the adjuvant setting. Also, 42% of Phase II trials do not measure any survival-related endpoint, and only 23% of Phase III trials assess the immune response to vaccination.ConclusionThe clinical trial effort in tumor vaccination is declining, necessitating a greater urgency in identifying and removing the obstacles to clinical translation. These obstacles may include: 1) vaccination against a small range of antigens; 2) naked delivery of antigen; 3) investigation of less immunogenic cancer types; and 4) investigation in the setting of established disease. In addition, the prevalence of late phase failure may be due to inadequate assessment of survival-related endpoints in Phase II trials. The clinical trial development of tumor vaccines should include mechanism-based translational endpoints, as well as the discovery of immune biomarkers with which to stratify, monitor, and prognosticate patients.

ObjectiveTo investigate the association between troponin positivity in patients hospitalised with COVID-19 and increased mortality in the short term.SettingHomerton University Hospital, an inner-city district general hospital in East London.DesignA single-centre retrospective observational study.ParticipantsAll adults admitted with swab-proven RT-PCR COVID-19 to Homerton University Hospital from 4 February 2020 to 30 April 2020 (n=402).Outcome measuresWe analysed demographic and biochemical data collected from the patient record according to the primary outcome of death at 28 days during hospital admission.MethodsTroponin positivity was defined above the upper limit of normal according to our local laboratory assay (>15.5 ng/L for females, >34 ng/L for males). Univariate and multivariate logistical regression analyses were performed to evaluate the link between troponin positivity and death.ResultsMean age was 65.3 years for men compared with 63.8 years for women. A χ2 test showed survival of patients with COVID-19 was significantly higher in those with a negative troponin (p=3.23×10−10) compared with those with a positive troponin. In the multivariate logistical regression, lung disease, age, troponin positivity and continuous positive airway pressure were all significantly associated with death, with an area under the curve of 0.889, sensitivity of 0.886 and specificity of 0.629 for the model. Within this model, troponin positivity was independently associated with short-term mortality (OR 2.97, 95% CI 1.34 to 6.61, p=0.008).ConclusionsWe demonstrated an independent association between troponin positivity and increased short-term mortality in COVID-19 in a London district general hospital.

Current NICE guidance recommends CT coronary angiography (CTCA) as first line for investigation of new onset stable chest pain, however; CTCA is not yet readily available in all UK centres. DSE remains recommended in current ESC guidance and provides a readily available, low cost alternative (1). Indeed, a negative test has been demonstrated to have an excellent negative predictive value in the region of >98% (2). Aim We sought to evaluate the rate of cardiac events within two years of a negative DSE. Methods We performed a retrospective data interrogation of all DSE's performed in the Mater Hospital Cardiac Investigations Department between 2017 and 2019. MACE was evaluated at two years. Data were extracted using local electronic healthcare records. Statistical analysis performed using SPSS software.Results 302 DSE's were performed during the study period. The mean age was 64.1±10.4years with 41.7% male. Of the population, 16.2% had a prior history of IHD with 19.2% being diabetic. All tests were requested by the Cardiology team on an outpatient. 15 patients had a positive test. At two years the negative predictive value of a negative DSE was 98.3%. A positive test had a sensitivity for predicting coronary artery disease of 86.7% with a false positive rate of approximately of 13.3%. The overall complication rate was low at 0.7%. Using a combined endpoint of time to ACS or revascularisation; there was a significant difference (p<0.001) in event free survival between groups (figure 1).Conclusion DSE is a safe test with a high sensitivity for detecting coronary artery disease. Furthermore, compared to a positive test, a negative test has a strong negative predictive value for cardiac events at two years.

ConclusionOur results are concordant with previous studies demonstrating that diagnostic accuracy of hTTE is heavily influenced by operator experience. It is less known how much training should be given to operators before hTTE assessment is reliable enough to base clinical decisions upon. However with simple education, we hope to demonstrate that discrepancy between hTTE and sTTE can be reduced. Moving forwards, we plan to introduce a dedicated training day for new ST3 cardiology trainees and observe how this influences performance. The discrepancy and underestimation with hTTE raises the question of clinical implications, particularly of underestimating MR. It may be the case that cardiology trainees should be more prudent when commenting on MR, spend slightly longer obtaining images if MR is present and liaise more closely with medical colleagues informing them about the limitations of HHE.Abstract 14 Figure 2 Graph demonstrating the proportion of underestimation and overestimation in discordant scans across each parameter Abstract 14 Table 1 Severity grading system used to assess left ventricular systolic function (LVSF), mitral regurgitation (MR), aortic regurgitation (AR) and aortic stenosis (AS) Abstract 14 Table 2 Table showing average error for each parameter pre-and post-intervention with respective weighted kappa statistics (κ) Kappa values of <0.2 were interpreted as poor, 0.21-0.4 as fair, 0.41-0.6 as moderate, 0.61-0.8 as good, and 0.Abstract 15 Figure 1 Case 1-severe disease in mid LAD (arrow) on invasive angiography (A) but no ischaemid scar on LGE imaging (B & C)

Objective: We performed a single-centre retrospective observational study investigating the association between troponin positivity in patients hospitalised with COVID-19 and increased mortality in the short term. Methods: All adults admitted with swab-proven RT-PCR COVID-19 to Homerton University Hospital (HUH) from 04.02.20 to 30.04.20 were eligible for inclusion. We retrospectively analysed demographic and biochemical data collected from the physical and electronic patient records according to the primary outcome of death at 28 days during hospital admission. Troponin positivity was defined above the upper limit of normal according to our local laboratory assay (>15.5ng/l for females, >34 ng/l for males). Univariate and multivariate logistical regression analyses were performed to evaluate the link between troponin positivity and death. Results: Mean length of stay for all 402 hospitalised COVID-19 patients at HUH was 9.1 days (SD 12.0). Mean age was 65.3 years for men compared to 63.8 years for women. A chi-squared test showed that survival of COVID-19 patients was significantly higher in those with a negative troponin (p = 3.23 x10-10) compared to those with a positive troponin. In the multivariate logistical regression, lung disease, age, troponin positivity and CPAP were all significantly associated with death, with an AUC of 0.8872, sensitivity of 0.9004 and specificity of 0.6292 for the model. Within this model, troponin positivity was independently associated with short term mortality (OR 3.23, 95% CI 1.53-7.16, p=0.00278). Conclusions: We demonstrated an independent association between troponin positivity and increased short-term mortality in COVID-19 in a London district general hospital.