tbuckley/cabot-search huggingface dataset:
AB0863 RADIOGRAPHY VERSUS ULTRASONOGRAPHY – WHICH IMAGING MODALITY TELLS US MORE ABOUT PAIN SEVERITY IN KNEE OSTEOARTHRITIS?
Authors: G. Gerganov, T. Georgiev, T. Shivacheva
Journal: Annals of the Rheumatic Diseases (2020)

Background: Osteoarthritis (OA) is a leading cause of disability worldwide and pain is its cardinal symptom. Ranging from structural injuries to central sensitization, multifactorial mechanisms play an important role in pain perception in patients with knee OA (KOA) defining a discrepancy between pain and structural damage. Imaging modalities such as radiography and musculoskeletal ultrasonography may assess those structural findings and both are well embedded in routine clinical practice. However, their association with pain severity is poorly studied. Objectives: To evaluate the place of X-ray- and ultrasound-derived parameters of structural damage for pain perception in knee osteoarthritis patients. Methods: Sixty-four knees from 38 patients with KOA fulfilling the ACR criteria were assessed. The pain severity was evaluated in all knees by 100-millimeters (mm) visual analogue scale (VAS). Anteroposterior radiographs of the fully extended knees in an upright weight-bearing position were obtained and images were evaluated according to the Kellgren-Lawrence (KL) and OARSI atlas. All patients were investigated with a portable MyLab 25 Gold system equipped with an LA435 transducer (Esaote SpA, Genoa, Italy) by two experienced ultrasonographers. The presence or absence of synovial thickening, effusion in the suprapatellar bursa, and popliteal cyst were assessed. Medial meniscal extrusion and medial and lateral femoral cartilage thickness (medial and lateral) were measured in mm in full extension and flexion position, respectively. Femoral osteophytes were semi-quantitatively scored using a scale consisted of four grades (0-3). Results: The levels of pain differed significantly in the KL groups (p = .001) and in the groups classified according to the medial tibiofemoral compartment narrowing defined in line with the OARSI atlas (p = .005). The other knee osteoarthritis radiographic characteristics derived from the OARSI atlas did not correlate with the pain. From the assessed ultrasound parameters, medial meniscal extrusion and medial femoral cartilage showed a weak correlation with pain levels (r = .254, p = .043; r = -.265, p = 0.034, respectively). Nevertheless, in the multivariate analysis after adjusting for age and BMI, both variables did not reach significance for explaining the differences in VAS levels. No association between the presence of synovial effusion and popliteal cyst and pain severity was found. Conclusion: Plain radiography and ultrasonography reflect different structural changes in osteoarthritis that may play an important role in pain perception. Both imaging modalities can complement each other in order to improve the evaluation of the patient with KOA. Acknowledgments: None Disclosure of Interests: None declared
AB1349-HPR IMPLEMENTATION OF A GROUP EDUCATION SERVICE FOR RHEUMATOLOGY OUTPATIENTS COMMENCING BIOLOGIC THERAPY AT UNIVERSITY COLLEGE LONDON HOSPITAL (UCLH)
Authors: M. Naja, E. Hawkins, S. Moore, M. Castelino
Journal: Annals of the Rheumatic Diseases (2020)

Background: Biologic therapies are commonly prescribed in a range of rheumatic conditions. From 2016 - 2018, a mean of 226 rheumatology outpatients at UCLH commenced biologic therapy per year for inflammatory arthritis alone 1 . Patient education is required prior to initiation. At UCLH this is delivered via individual appointments with specialist nurses, contributing to waiting times for nurse appointments and thus delays in starting treatment. Objectives: 1.To evaluate patient satisfaction following group education. 2.To reduce the burden on specialist nurses delivering multiple individual sessions. Methods: A once-weekly group education service was set up at UCLH. This comprised: an oral PowerPoint presentation; injection demonstration; question and answer session; and written leaflets. Patients were provided with pre- and post-session questionnaires to evaluate the service. Results: Over the first five weeks of the service, 18 patients attended group education (a median of 4 patients per session). Nine patients (50%) had previously researched the medication via internet search engines. Patients’ questions prior to the session were most commonly centred on side effects and long-term risks. All of the patients (100%) felt that “most or all” of their questions were answered during the session. Patients gave their awareness of the reason for therapy a median score of 7/10 pre-education; this rose to a median of 10/10 post-education. The median score given for confidence to self-administer the drug was 5.5/10 pre-education; this rose to a median of 10/10 post-education. The median anxiety score was 3/5 pre-education; this dropped to 2/5 post-education. The presentation was adapted based on questions that arose during the sessions. Multiple patients gave informal, verbal feedback stating that they found the group environment to be beneficial, providing a chance to meet others with similar conditions, share experiences and feel reassured that they are not alone in starting biologic therapy. Conclusion: Patient feedback demonstrated that the group education sessions at UCLH were effective in improving their understanding of the rationale for biologic treatment, increasing their confidence in self-administration, and reducing anxiety. Verbal feedback illustrated that many patients enjoyed the group environment, and the opportunity to interact and share experiences with others. At an average rate of 4 patients currently being seen a week, it is estimated that this will save 192 specialist nurse appointments per year (out of an estimated 226 commencing biologic therapy). There is scope for further research into the effects that this has had on waiting times to receive education / start treatment, and on drug compliance. References: [1]Greenwood, Mandy. UCLH Rheumatology Database. UCLH, 2020. Disclosure of Interests: None declared
Abstract PL01-01: Personal regulome navigation of cancer
Authors: Howard Y. Chang
Journal: Cancer Research (2020)

Abstract Cancer is a disease of genes. Yet the elucidation of cancer genomes does not mean we have conquered cancer; the central challenge is in their interpretation. In every human cell, two meters of DNA is packed into a ~10 micron nucleus. The genome is extensively compacted, except for the active regulatory DNA elements that remain accessible. I will describe new technologies based on DNA transposition that reveals the epigenomic profiles of single cells or from clinical biopsies of disease states. The landscape of active DNA regulatory elements are further linked to 3D genome architecture, mutational profiles, and RNA output to reveal the targets of disease associated DNA elements, such as inherited genetic variants or those modified by environmental stimuli. Our analysis of 23 human cancer types reveal nearly half a million active DNA elements across human cancers, disclose oncogenic extrachromosomal DNA, and identify gene-regulatory interactions underlying cancer immune evasion. These results suggest a systematic approach to understanding the noncoding genome in cancer to advance diagnosis and therapy. Citation Format: Howard Y. Chang. Personal regulome navigation of cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr PL01-01.
Abstract 15537: Poor Recovery From Receptor Tyrosine Kinase Inhibitor Cardiotoxicity is Linked to Toxic Effects on Cardiac Stem Cells
Authors: Andrew J Smith, Prashant Ruchaya, Robert Walmsley, Kathleen E Wright, Bernardo Nadal-Ginard, Georgina M Ellison-Hughes
Journal: Circulation (2018)

Introduction: Receptor tyrosine kinase inhibitors (RTKIs) improve cancer survival but have cardiotoxic side effects, the mechanisms for which warrant further investigation. Endogenous cardiac stem ...
Abstract 13130: The Fontan Immunophenotype and Post-Transplant Outcomes in Children: A Multi-Institutional Study
Authors: Benjamin S Mantell, Estela Azeka, Ryan S Cantor, Waldemar F Carlo, Maryanne Chrisant, John C Dykes, Timothy M Hoffman, James K Kirklin, Devin Koehl, Thomas J L’Ecuyer, Jennie M McAllister, Adriana C Prada-Ruiz, Marc E Richmond
Journal: Circulation (2019)

Introduction: Patients (pts) after Fontan palliation often have an altered immunophenotype with lymphopenia (L) and hypogammaglobinemia that may be exacerbated by protein losing enteropathy (PLE, P...
Abstract IA22: Realizing the potential of targeted therapy in non-muscle invasive bladder cancer
Authors: Peter C. Black
Journal: Clinical Cancer Research (2020)

Abstract Targeted therapies have revolutionized the management of most cancers, but the era of targeted therapy has mostly passed by bladder cancer. Ramicurimab (targeting VEGR) and erdafitinib and infigratinib (both targeting FGFR) have recently provided some reason for optimism that targeted therapies with highly potent inhibitors may yet find a role in advanced bladder cancer. Targeting genomic alterations in FGFR3 holds the most promise, but this molecular event is probably even more relevant in non-muscle invasive bladder cancer (NMIBC), and trials in this space are essential. Similarly, KDMT6a appears to be particularly important in NMIBC, and drugs targeting chromatin modification pathways are likely to be relevant in NMIBC. Novel therapies are also under development that are not specific to an individual cancer's genomic makeup, but instead target specific cancer-related pathways. Such agents include oportuzumab monatox and BC-819. Most clinical trial activity has focused on BCG-unresponsive high-risk NMIBC patients, but this is partly due to the pathway for drug registration, and we are likely to see some of the successful drugs in this disease state move forward to earlier disease states, especially to intermediate-risk patients. These therapies will need to be positioned in the treatment landscape along with other nontargeted intravesical agents such as nadofaragene firadenovec (rAd-IFN) and systemic immune checkpoint blockade. Citation Format: Peter C. Black. Realizing the potential of targeted therapy in non-muscle invasive bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA22.
Abstract IA21: Intravesical gene therapy for NMIBC
Authors: Sharada Mokkapati, Jon Duplisea, Michael Metcalfe, Amy Lim, Vikram Narayan, Devin Plote, Debashish Sundi, James E. Furguson, Nigel R. Parker, Seppo Yla-Herttuala, David McConkey, Kimberly S. Shluns, Colin P.N. Dinney
Journal: Clinical Cancer Research (2020)

Abstract BCG is our most effective therapy for treating NMIBC, but over time, most patients will eventually recur. Alternative therapies to avoid cystectomy are needed as to date, only valrubicin, with a CR approaching 10% at 12 months in BCG-refractory CIS, has been FDA approved. Significant unmet need thus remains for an effective second-line therapy for patients facing cystectomy. The elucidation of a pathway for registration of new agents for BCG-unresponsive NMIBC has drawn the attention of pharma, and a variety of new approaches are under evaluation. Gene therapy is a promising approach for the management of BCG-unresponsive NMIBC. Effective gene transfer across the urothelium has been accomplished, and several agents are being evaluated in ongoing clinical trials. Coldgenesys reported a 47% CR at 6 months for BCG-unresponsive NMIBC using a replication-competent oncolytic adenovirus. The SUO CTC reported a 35% RFS at 12 months for patients treated with rAd-IFNα2b/Syn3 gene therapy in a phase II trial. The RFS for patients with papillary disease was 50% and the CR for patients with CIS was 30%. The SUO-CTC have recently completed recruitment for the phase III trial and further preclinical work has progressed to elucidate rAd-IFN/Syn3 treatment efficacy via predictive efficacy biomarkers for patient selection, vectors that might improve transduction efficiency and the design of novel therapeutic combination strategies to take advantage of rAd-IFN's immunologic activity. Citation Format: Sharada Mokkapati, Jon Duplisea, Michael Metcalfe, Amy Lim, Vikram Narayan, Devin Plote, Debashish Sundi, James E. Furguson III, Nigel R. Parker, Seppo Yla-Herttuala, David McConkey, Kimberly S. Shluns, Colin P.N. Dinney. Intravesical gene therapy for NMIBC [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA21.
Extracorporeal Membrane Oxygenation for Critically Ill Patients with COVID-19–related Acute Respiratory Distress Syndrome: Worth the Effort!
Authors: Tobias Wengenmayer, Ralf M. Muellenbach, Fabio Silvio Taccone, Markus Kredel, Armin Kalenka, Jan Bělohlávek, Tobias Spangenberg, Hendrik Haake, Hendrik Bracht, Onnen Moerer, Roberto Lorusso, Philipp M. Lepper
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
A Biomimetic Nano‐Engineered Platform for Functional Tissue Engineering of Cartilage Superficial Zone
Authors: Dorsa Dehghan‐Baniani, Babak Mehrjou, Paul K. Chu, Hongkai Wu
Journal: Advanced Healthcare Materials (2020)

Abstract Articular cartilage has limited regeneration capacity because of its acellular and avascular nature. Although tissue engineering has been shown to be life‐saving, reforming cartilage zones required by the appropriate tissue functions are challenging. Herein, the need is addressed by designing and producing a nano‐engineered structure mimicking the superficial zone (SZ) of articular cartilage. The substrate is based on silk with good mechanical properties in conjunction with nano‐topographical and biochemical cues. Nanopillar arrays are produced on the silk surface to regulate the stem cell morphology rendering them with a flattened ellipsoidal shape that is similar to that of chondrocytes in the SZ of natural cartilage. The cell interactions are enhanced by nitrogen ion implantation and the biomolecule, kartogenin (KGN), is loaded to promote chondrogenesis of the stem cells and furthermore, a thermosensitive chitosan hydrogel is formed on the nanopatterned silk to produce rheological properties similar to those of a synovial fluid. Based on the in vitro results and mechanical properties, it is a desirable implantable smart structure mimicking the cartilage SZ with the ability of continuous drug release for cartilage regeneration.
Management and Outcomes of Patients With STEMI During the COVID-19 Pandemic in China
Authors: Dingcheng Xiang, Xin Xiang, Wei Zhang, Shaodong Yi, Jinxia Zhang, Xiaolong Gu, Yawei Xu, Kai Huang, Xi Su, Bo Yu, Yan Wang, Weiyi Fang, Yong Huo, Junbo Ge
Journal: Journal of the American College of Cardiology (2020)

ST-segment elevation myocardial infarction (STEMI) is a fatal cardiovascular emergency requiring rapid reperfusion treatment. During the coronavirus disease-2019 (COVID-19) pandemic, medical professionals need to strike a balance between providing timely treatment for STEMI patients and implementing infection control procedures to prevent nosocomial spread of COVID-19 among health care workers and other vulnerable cardiovascular patients.This study evaluates the impact of the COVID-19 outbreak and China Chest Pain Center's modified STEMI protocol on the treatment and prognosis of STEMI patients in China.Based on the data of 28,189 STEMI patients admitted to 1,372 Chest Pain Centers in China between December 27, 2019 and February 20, 2020, the study analyzed how the COVID-19 outbreak and China Chest Pain Center's modified STEMI protocol influenced the number of admitted STEMI cases, reperfusion strategy, key treatment time points, and in-hospital mortality and heart failure for STEMI patients.The COVID-19 outbreak reduced the number of STEMI cases reported to China Chest Pain Centers. Consistent with China Chest Pain Center's modified STEMI protocol, the percentage of patients undergoing primary percutaneous coronary intervention declined while the percentage of patients undergoing thrombolysis increased. With an average delay of approximately 20 min for reperfusion therapy, the rate of in-hospital mortality and in-hospital heart failure increased during the outbreak, but the rate of in-hospital hemorrhage remained stable.There were reductions in STEMI patients' access to care, delays in treatment timelines, changes in reperfusion strategies, and an increase of in-hospital mortality and heart failure during the COVID-19 pandemic in China.
Pharmacokinetic, Pharmacodynamic and Blood Analytes Associated with Clinical Response and Safety in Relapsed/Refractory Aggressive B-NHL Patients Treated with JCAR017
Authors: Mark Heipel, Jeffrey Smith, William Brown, Mandana Karimi, Benhuai Xie, Daniel Li, Tina Albertson, Jacob Garcia, Todd Devries, Claire L Sutherland
Journal: Blood (2017)
Abstract IA25: Molecular biomarkers of chemoradiation response in bladder preservation therapy
Authors: David T. Miyamoto
Journal: Clinical Cancer Research (2020)

Abstract The standard definitive treatment options for muscle-invasive bladder cancer are radical cystectomy or bladder-sparing trimodality therapy (TMT), consisting of maximal transurethral resection of bladder tumor followed by chemoradiation therapy. Although multiple series show these two treatment approaches have similar overall long-term outcomes, recent studies suggest that molecular biomarkers may identify subgroups of patients who may preferentially benefit from one type of therapy over the other. Such biomarkers include tumor-intrinsic genes involved in DNA repair and signal transduction, which confer sensitivity or resistance to radiation therapy based on the intrinsic biology of the tumor. Emerging biomarkers also include molecular signatures of the tumor microenvironment, suggesting an important role for tumor-extrinsic factors in governing therapeutic sensitivity or resistance. This presentation will review the evidence and rationale underlying potential prognostic and predictive molecular biomarkers in bladder preservation therapy. A specific focus will be on our recent gene expression profiling of 136 muscle-invasive bladder cancer patients treated with bladder-sparing TMT. Our analysis showed that higher immune infiltration was associated with improved disease-specific survival after TMT, whereas higher stromal infiltration was associated with shorter disease-specific survival in a comparison cohort treated with radical cystectomy after neoadjuvant chemotherapy. These findings require validation studies in additional cohorts, which are currently ongoing. An additional focus of the presentation will be on emerging liquid biopsy biomarkers of minimal residual disease after bladder cancer therapy. The standard follow-up for patients after bladder-sparing TMT includes cystoscopies with biopsies and imaging studies at regular intervals. Liquid biopsy approaches such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) may enable noninvasive monitoring of response and detection of minimal residual disease after therapy, with a substantial lead time over conventional follow-up approaches including imaging. If validated in prospective clinical trials, molecular biomarkers may guide the tailored selection of appropriate treatments for individual patients with muscle-invasive bladder cancer, as well as enable noninvasive monitoring of patients after therapy. Such biomarkers also have potential to guide the use of synergistic combinations of immunotherapy with chemoradiation therapy for bladder cancer. Citation Format: David T. Miyamoto. Molecular biomarkers of chemoradiation response in bladder preservation therapy [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA25.
Abstract 10715: Spanish-speaking Heart Failure Patients Perceive Increased Confidence and Health Communication Skills Following a Spanish-language Self-care Intervention
Authors: Jill H Esquivel, Linda K Ottoboni, Lucy Selman
Journal: Circulation (2019)

Introduction: Patient education is essential for HF self-care. Hispanic/Latino Americans are the largest US ethnic group and have a higher incidence of HF hospital admissions than non-Hispanic whit...
Abstract IA04: Molecular alterations in variant morphology
Authors: Donna E. Hansel
Journal: Clinical Cancer Research (2020)

Abstract Bladder cancer can be divided into several major subtypes that include urothelial carcinoma, squamous cell carcinoma, adenocarcinoma and neuroendocrine carcinoma. Urothelial carcinoma, the most common form of bladder cancer, is further subdivided into numerous histologic variants based on distinct morphologic features. While histologic characterization remains the most important factor in diagnosis and patient management, emerging molecular data across bladder cancer subtypes and variants may potentially alter how bladder cancer is classified. Large scale -omic analytics have uncovered unique signatures within major bladder cancer subtypes. In addition, molecular groupings and unique single-gene alterations have been identified within urothelial carcinoma and its many morphologic variants, including plasmacytoid urothelial carcinoma and micropapillary urothelial carcinoma. We will review molecular alterations in major categories of bladder cancer and urothelial carcinoma variants. Many of these molecular alterations could potentially be used in revised classification, diagnosis, and therapy of bladder cancer. Citation Format: Donna E. Hansel. Molecular alterations in variant morphology [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA04.