564 Freedom from Urethral Catherisation – Using QI Methodology to Improve Patient Outcome and Experiences

Aim To reduce catheter burden on patients who could instead be free of urethral catheter and taught intermittent self-catheterisation (ISC). Method 2 PDSA (Plan, Do, Study, Act) cycles were performed over a 21-month period from February 2018 to November 2020. Using multiple nurse-led TWOC clinics, data was extracted using nurse-completed proformas and electronic patient records to determine: TWOC rate; urethral catheter-free rate; and ISC rate. Following baseline measurement, interventions were made, such as centralisation of TWOC services, emphasis on ISC teaching and the introduction of industry-nurse led clinics. Results At baseline, TWOC rate, urethral catheter-free rate and ISC rate were 55.7%, 68% and 28.2%, respectively. Following centralisation of TWOC services and emphasis on ISC teaching in Cycle 1, urethral catheter-free rate rose to 77.8% whilst ISC rate fell to 25%. Cycle 2 followed the introduction of industry-nurse led clinics. Following this, urethral catheter-free rate rose further to 81.6%, with ISC rate rising dramatically to 56.3% Conclusions To those capable, ISC frees patients of catheter burden and its sequalae. Evidently, a greater onus on ISC training will increase the number of patients left catheter-free.

Challenges and opportunities in improving left ventricular remodelling and clinical outcome following surgical and trans-catheter aortic valve replacement

Over the last half century, surgical aortic valve replacement (SAVR) has evolved to offer a durable and efficient valve haemodynamically, with low procedural complications that allows favourable remodelling of left ventricular (LV) structure and function. The latter has become more challenging among elderly patients, particularly following trans-catheter aortic valve implantation (TAVI). Precise understanding of myocardial adaptation to pressure and volume overloading and its responses to valve surgery requires comprehensive assessments from aortic valve energy loss, valvular-vascular impedance to myocardial activation, force-velocity relationship, and myocardial strain. LV hypertrophy and myocardial fibrosis remains as the structural and morphological focus in this endeavour. Early intervention in asymptomatic aortic stenosis or regurgitation along with individualised management of hypertension and atrial fibrillation is likely to improve patient outcome. Physiological pacing via the His-Purkinje system for conduction abnormalities, further reduction in para-valvular aortic regurgitation along with therapy of angiotensin receptor blockade will improve patient outcome by facilitating hypertrophy regression, LV coordinate contraction, and global vascular function. TAVI leaflet thromboses require anticoagulation while impaired access to coronary ostia risks future TAVI-in-TAVI or coronary interventions. Until comparable long-term durability and the resolution of TAVI related complications become available, SAVR remains the first choice for lower risk younger patients.

Identification of distinct immune landscapes using an automated nine-color multiplex immunofluorescence staining panel and image analysis in paraffin tumor tissues

Immune profiling is becoming a vital tool for identifying predictive and prognostic markers for translational studies. The study of the tumor microenvironment (TME) in paraffin tumor tissues such as malignant pleural mesothelioma (MPM) could yield insights to actionable targets to improve patient outcome. Here, we optimized and tested a new immune-profiling method to characterize immune cell phenotypes in paraffin tissues and explore the co-localization and spatial distribution between the immune cells within the TME and the stromal or tumor compartments. Tonsil tissues and tissue microarray (TMA) were used to optimize an automated nine-color multiplex immunofluorescence (mIF) panel to study the TME using eight antibodies: PD-L1, PD-1, CD3, CD8, Foxp3, CD68, KI67, and pancytokeratin. To explore the potential role of the cells into the TME with this mIF panel we applied this panel in twelve MPM cases to assess the multiple cell phenotypes obtained from the image analysis and well as their spatial distribution in this cohort. We successful optimized and applied an automated nine-color mIF panel to explore a small set of MPM cases. Image analysis showed a high degree of cell phenotype diversity with immunosuppression patterns in the TME of the MPM cases. Mapping the geographic cell phenotype distribution in the TME, we were able to identify two distinct, complex immune landscapes characterized by specific patterns of cellular distribution as well as cell phenotype interactions with malignant cells. Successful we showed the optimization and reproducibility of our mIF panel and their incorporation for comprehensive TME immune profiling into translational studies that could refine our ability to correlate immunologic phenotypes with specific patterns of cells distribution and distance analysis. Overall, this will improve our ability to understand the behavior of cells within the TME and predict new treatment strategies to improve patient outcome.

Development TACI and Bcma Dual-Antigen Targeted Immunotherapy for Multiple Myeloma

Introduction: Despite recent advances in treatment for multiple myeloma(MM), there remains a need for novel therapeutic approaches. Recently, we have reported that antigen-specific CD8+ cytotoxic T lymphocytes (CTL) with anti-MM activity can be induce by immunogenic peptides to XBP1 (X-box binding protein 1), CD138 (Syndecan-1) and CS1 (SLAMF7). Based on these results, multicenter Phase 1/2a trials are completed in patients with smoldering multiple myeloma (SMM) (JAMA Oncol.2018) and on-going in patients with SMM or triple negative breast cancer, alone and in combination with checkpoint inhibitors, lenalidomide, and HDAC6 inhibitor. We here expand the breadth and extent of MM-specific immunotherapies by targeting additional tumor-associated antigens, including B-cell maturation antigen (BCMA) and transmembrane activator and CAML interactor (TACI), TNF receptor family proteins which are involved in maturation of B-cells and highly expressed in MM. Purpose: We aim to develop a dual antigen targeted immunotherapeutic approach to induce central memory-specific anti-MM immunity and improve patient outcome. Results: We demonstrated that engineered BCMA72-80 (YLMFLLRKI) and BCMA54-62 (YILWTCLGL) peptides can evoke BCMA-specific CTL and their specific activities against MM (Bae et al. 2019). Here, we report the identification of a novel heteroclitic TACI peptide with improved HLA-A2 binding/stability compared to the native TACI peptides. The heteroclitic TACI peptide induces antigen-specific memory CD8+ CTL with robust anti-tumor activities (CD107a degranulation, Granzyme B upregulation, Th1 cytokine production) against HLA-A2+ MM (U266, McCAR) cells, but not against HLA-A2- MM (OPM2, RPMI) nor HLA-A2+ breast cancer (MDA-MB231) cells. In response to HLA-A2+ MM cells, the heteroclitic TACI peptide-specific CTL showed the antigen-specific proliferation of CD8+ CTL expressing costimulatory molecules (CD28 > 41BB > CD40L), which was directly associated with functional anti-tumor activity. These results suggest that the heteroclitic TACI peptide identified is a potential novel therapeutic option to effectively generate TACI-specific CD8+ memory CTL targeting MM. In on-going studies, we are evaluating a combination of immunogenic heteroclitic peptides specific to BCMA and TACI to induce highly functional antigen-specific immune responses by CD8+ Tc and CD4+ Th cells to efficiently target tumor cells. Conclusions: A novel heteroclitic TACI peptide can induce MM-specific central memory CD8+ CTL with robust poly-functional anti-tumor activities. These results provide the framework for therapeutic application targeting combination TACI and BCMA antigens in MM patients, alone and in combination with checkpoint inhibitors, epigenetic regulators and immune modulators, to both enhance anti-MM immunity and improve patient outcome. Disclosures Richardson: Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding. Munshi:Oncopep: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Celgene: Consultancy; Adaptive: Consultancy; Abbvie: Consultancy. Anderson:Oncopep: Other: Scientific Founder; Amgen: Consultancy, Speakers Bureau; Sanofi-Aventis: Other: Advisory Board; Bristol-Myers Squibb: Other: Scientific Founder; Janssen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau.

Role of a Checklist to Improve Patient Safety in Interventional Radiology

A checklist can be defined as a comprehensive formal list of essential actions to be taken in a specific fashion. This concept has been extended from the aviation industry to health care to improve patient outcome and patient satisfaction with a significant reduction in complication rates. This review article aims to assess the importance and benefits associated with the use of a well-formulated checklist while performing the various minimally invasive image-guided procedures. Various databases including PubMed, Medline, Scopus, and Cochrane were searched for using various keywords including “Checklist,” “Radiology,” “Interventional Radiology,” “Image-Guided Procedure,” and “minimally invasive procedure.” The use of a checklist is the way ahead especially when patients today require minimal risk but demand high-quality care. Implementation of such an easy-to-perform tailor-made mechanism can significantly improve patient outcome and patient satisfaction.