tbuckley/cabot-search huggingface dataset:
Specialized new patient scheduling unit to improve patient access.
Authors: Tony Philip, Karen Gleason, Rosemarie Weisman
Journal: Journal of Clinical Oncology (2019)

131 Background: New patient unit is responsible for scheduling initial appointment, obtaining pertinent medical records and pathology slides prior to initial visit. Original workflow utilized dedicated schedulers to answer new patient appointment phone calls and emails, obtain patient demographics, brief medical history, and financial counseling referral. A separate chart preparation team gathered records for clinical review by two nurse navigators the day prior to the appointment. There were on average 6 patients/day waiting for appointments on the Pending List and phone wait times were thought to contribute to abandoned call rate and missed appointments. Methods: A workgroup of administrators, schedulers and clinicians was formed to redesign the workflow. The new workflow, starting April 2018, combined new patient and chart preparation team and divided them into three disease specific scheduling teams. Based on appointment volume, there is Team 1 Breast/GYN, Team 2 GI/GU/Thoracic/Head &amp; Neck, Team 3 Malignant/Benign Hematology. Team members are responsible for answering phones, completing intake, and gathering records customized to needs of the specific care teams and enabled nurse navigator to be deployed elsewhere. Results: New workflow has reduced call volume, wait time, call abandonment and no show rates with increased new patient visits. Conclusions: Creating sub-specialty based scheduling teams to work with the clinical team has improved patient access to cancer care and reduced wait time. Further steps are being taken to further streamline process. [Table: see text]
Feasibility of collecting survey-based patient-reported outcome measures (PROMs) from patients living with advanced cancer: Emerging findings from the Living with Colorectal Cancer study.
Authors: Marc Kerba, Shireen Kassam, Crystal Beaumont, Patricia Biondo, Madalene Earp, Patricia A. Tang, Jessica Simon, Sharon Watanabe, Aynharan Sinnarajah
Journal: Journal of Clinical Oncology (2019)

207 Background: The “Living with Colorectal Cancer study” seeks to characterize the experiences of patients diagnosed with advanced colorectal cancer to inform care improvements. Here we describe our experiences recruiting patients and collecting patient reported outcome measures (PROMs). Methods: Eligible patients were identified by oncologists in Alberta, Canada’s two tertiary cancer centres and approached for consent to participate during routine appointments. Following baseline surveys, participants were given a choice of completing monthly surveys via email, phone, post, or in person. We purposively chose previously validated surveys already in use provincially, including EQ-5D-5L and Putting Patients First. We endeavoured to include non-English speaking participants by providing translated study materials and interpretation. Results: In one year of recruitment, 88 patients were enrolled. Edmonton, Alberta’s patient recruitment (N = 62) is double that of Calgary, Alberta (N = 26), despite similar population sizes. In Calgary and Edmonton, 81% and 56% of participants chose email-based PROMs surveys, respectively. The current missing survey rate is 12% (i.e. surveys not completed per month). Forty-eight participants (55%) completed ≥6 sets of monthly PROMs data; 26 (30%) transferred “off study” (61% of which died). Several participants expressed the desire to describe their experiences beyond what the surveys could accommodate. Despite language accommodation, all participants chose to complete surveys in English; however, 21% reported speaking another language daily. Conclusions: It is challenging but possible to engage and retain patients with advanced cancer in research focused on PROMs. Speaking with patients face-to-face in cancer clinics increased the burden on healthcare providers (i.e. clinic flow and time spent with patients), but appears to be a practical and appropriate way to recruit participants. Offering multiple methods of communication allowed patients to participate in a manner most practical for their lifestyle and did not impact PROMs collection. Clinical trial information: NCT03572101.
Abstract 845: Distinctive Inflammatory and Fibrotic Signature of Extracellular Vesicles from Epicardial Fat of Patients with Atrial Fibrillation
Authors: Olga Shaihov-Teper, Eilon Ram, La-Paz Levin-Kotler, Nili Naftali-Shani, Jonathan Leor
Journal: Circulation Research (2019)

Background and Aim: Epicardial fat (eFat) has been linked to atrial remodeling and fibrillation (AF). We aimed to determine whether extracellular vesicles (EVs) derived from eFat play a role in the pathogenesis of AF. Methods and Results: We collected small specimens of eFat from patients (pts) with and without (w/o) AF undergoing heart surgery. eFat specimens were incubated as organ cultures and EVs were isolated from the culture medium by ultra-centrifugation. We used immunoblotting, electron microscopy, and nanoparticle tracking analysis to characterize the EVs ( Fig. A-C ). Significantly, eFat specimens from AF pts secreted greater amounts of EVs compared with patients w/o AF ( Fig. D ). Moreover, eFat EVs from AF pts secreted a higher concentration of inflammatory and fibrotic cytokines but less anti-inflammatory cytokines, compared with patients w/o AF ( Fig. E-H ). Notably, EV cytokines reflected the inflammatory and fibrotic status of eFat in AF pts better than free cytokines ( Fig. I-L ). Next, we tested several miRNA that could influence cardiac fibrosis. For example, miR-133 inhibits TGF-β, decreases collagen content and inhibits atrial remodeling. Expression of EV miR-133 was lower in eFat of AF pts than in patients w/o AF ( Fig. M ). Eventually, “wound healing” scratch assay show that fibroblast migration was greater after incubation with eFat EVs from AF patients, compared with pts w/o AF. ( Fig. N ). Conclusions: eFat from AF patients secretes a higher number of EVs with an inflammatory and fibrotic profile. Our findings suggest that eFat EVs contribute to inflammation and fibrosis, both of which contribute to the pathogenesis of atrial remodeling and fibrillation.
Abstract 497: Studying Cardiovascular Effects of Marijuana on Healthy Individuals Using Human Derived Induced Pluripotent Stem Cells
Authors: Tzu-Tang " Wei, Mark Chandy, Ian Y Chen, Hung-Ta Wo, Saereh Khanamiri, Masataka Nishiga, Fritz Seidl, Nazish Sayed, Chun Liu, June-Wha Rhee, Detlef Obal, Tony Chour, Joseph C Wu
Journal: Circulation Research (2019)

Marijuana is the most widely used illicit drug worldwide. Epidemiological studies indicate that marijuana increases the risk of coronary artery disease (CAD). Adverse cerebrovascular and peripheral vascular effects are also associated with marijuana use. In addition, three synthetic cannabis drugs have been approved by the FDA for treating chemotherapy-induced nausea and vomiting, which also show cardiovascular side effects. Thus, both medical and recreational marijuana have adverse cardiovascular side effects. Cannabinoid CB1 receptor signaling is involved in a variety of pathophysiological processes and selective CB1 antagonists show therapeutic potential. However, the current repertoire of CB1 antagonists has psychiatric side effects and limited application. Therefore, developing new CB1 antagonists are an unmet and growing clinical need with marijuana use on the rise. Here we found compound JW-1, an isoflavone abundantly presenting in soybeans, partially docked into the CB1 receptor and inhibited CB1 activity, suggesting that compound JW-1 was a novel CB1 antagonist. Human endothelial cells were more sensitive to Δ 9 -tetrahydrocannabinol (Δ 9 -THC) than cardiomyocytes and cardiac fibroblasts. To determine the mechanism of Δ 9 -THC pathological effects on the vasculature, we generated human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) from 5 healthy individuals. CB1 receptor was expressed in all hiPSC-ECs, whilst CB2 expression was low. Δ 9 -THC induced inflammation and oxidative stress via NF-κB signaling activated in hiPSC-ECs. Knockdown of CB1 receptor with siRNA, abrogation of receptor expression with CRISPRi and compound JW-1 treatment could rescue the effect of Δ 9 -THC. Furthermore, compound JW-1 blocked Δ 9 -THC-induced endothelial dysfunction in mice models. Our investigations reveal that Δ 9 -THC causes endothelial dysfunction via the CB1 receptor. Compound JW-1 is a novel CB1 antagonist that can be used for preventing Δ 9 -THC-induced side effects.
Abstract 937: Etv2 Regulates Endothelial Gene Expression With Its Novel Binding Partner Vezf1
Authors: Satyabrata Das, Bhairab N Singh, Wuming Gong, Erik Skie, Daniel J Garry, Mary G Garry, Vinayak Gupta, Joshua Theisen
Journal: Circulation Research (2019)

Ets transcription factors function as important developmental regulators and are known to be modulators of cell fate. Previously, in conjunction with co-factors, we have described Ets variant 2 (Etv2) as an essential regulator of the hematopoietic and endothelial lineages. But the mechanism and the Etv2 interacting partners involved in achieving this critical function remains poorly understood. Through Yeast two-hybrid analysis we identified Vascular Endothelial Zinc Finger 1 (Vezf1) as an interacting factor with Etv2. Vezf1 is a conserved C2H2 zinc finger transcription factor known to regulate the formation, proliferation, and migration of endothelial cells through several gene targets. We verified Vezf1 as a binding partner of Etv2 through co-immunoprecipitation and GST-pull down studies. Bioinformatic analysis of ChIP-seq and Etv2-expressing single cell RNA sequencing was conducted to identify candidate genes containing both Etv2 and Vezf1 binding motifs in their regulatory regions. Histone deacetylase 7 (Hdac7) and angiomotin like protein 2 (Amotl2) were identified as genes of interest involved in endothelial development. Hdac7 is a conserved class II deacetylase that functions in endothelial cell adhesion and vascular integrity. Amotl2 is a Motin family protein that functions in angiogenesis, endothelial cell polarity and migration. RT-qPCR analysis showed upregulation of Hdac7 and Amotl2 in response to doxycycline inducible Etv2 and Vezf1; whereas significant reduction of expression of these two genes was observed in the Etv2 and Vezf1 knockout cells. Chromatin immunoprecipitation (ChIP) and electrophoresis mobility shift assays (EMSA) confirmed Etv2-Vezf1 adjacent binding sites in the promoters of Hdac7 and Amotl2. Histone Acetyl transferase (HAT) assays was performed to investigate Etv2-Vezf1 on global histone acetylation conditions in doxycycline inducible embryoid bodies. Vezf1 overexpression results in a significant reduction of acetylated histone. In summary, this study identifies Vezf1 as a novel binding partner of Etv2 and their combined role in regulating downstream target genes Amotl2 and Hdac7 in hematoendothelial development.
Abstract P277: Exercise is Associated With Social Network Characteristics Among South Asian Immigrants
Authors: Mitali Thanawala, Juned Siddique, Andrew Cooper, John A Schneider, Swapna Dave, Alka M Kanaya, Namratha R Kandula
Journal: Circulation (2018)

Objective: Low physical activity increases cardiovascular disease (CVD) risk. Social context, operationalized through social networks, has been shown to drive health behaviors. This study examined the association between personal social networks and moderate-to-vigorous leisure-time physical activity (LTPA) among South Asian (Indian, Pakistani, Bangladeshi, Sri Lankan, Nepalese) immigrants, a group with high CVD rates. Methods: This study used cross-sectional data from an ancillary study of social networks (2014-2017) in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study cohort. Participants, free from CVD at baseline and living in the San Francisco Bay-area, CA and Chicago, IL, were administered a detailed social networks questionnaire and physical activity questionnaire adapted from the Cross-Cultural Activity Participation Study. Participants reported on the exercise behaviors of each social network member and if they exercised with the network member. Network members who exercised with a participant were categorized as exercise partners. Moderate-vigorous LTPA was calculated as Metabolic Equivalent of Task (MET) minutes per week. Sex-stratified, linear regression models were used to examine associations between social network characteristics and MET-min/week of LTPA, independent of age, marital status, and network size. The effect of having an exercise partner in the network, above simply having network members who exercised, was tested using a partial F-test to compare nested models. Results: Among the 700 participants, this analysis only included the 89% who reported any LTPA (n=623, 43% female). These individuals reported a median of 1335 MET-min/week of LTPA (IQR=735-2212 MET-min/week) and had an average of 4 network members (SD +/- 1). The proportion of network members who exercised was 0.89, and the proportion of exercise partners was 0.28. Exercise partners were most commonly spouses (56%) and friends (20%). Among South Asian men who exercised, having a social network member who exercised instead of having a non-exercising network member, significantly increased LTPA by 310 MET-min/wk (95% CI=152-470). For men, having a social network member who was an exercise partner instead of a non-exercising network member, was associated with an additional 520 MET-min/wk of LTPA (95% CI= 344-696). The effect on LTPA of having an exercise partner in the network was significantly greater than the effect of simply having a network member who exercised (p-value &lt; 0.001). Results were similar for women, but not statistically significant (p-value=0.05). Conclusions: Among South Asian immigrants, having an exercise partner in one’s personal social network was associated with significantly more LTPA. Social network support, in the form of an exercise partner, may be an effective component of interventions to promote LTPA in South Asians.
Improving the Outcomes of Acute Promyelocytic Leukemia in a Limited Resources Setting: The Benefit of Early ATRA Administration in 30-Day Survival
Authors: Bruno Kosa Lino Duarte, Ana Carolina Mourão Toreli, Mariana Dos Santos Pastori, Paulo Vittor Oliveira Peres, Andreza Lamonica, Camilla Maria de Alencar Saraiva, Eduardo Magalhães Rego, Katia B Pagnano
Journal: Blood (2018)
Examining patient and visit characteristics associated with the cancer patient experience.
Authors: Erica Bridge, Simron Singh, Amanda Murdoch, Mindaugas Mozuraitis, Brett Nicholls, Lesley Moody
Journal: Journal of Clinical Oncology (2019)

204 Background: Your Voice Matters (YVM) is a 28-item patient experience survey for adult cancer outpatients undergoing treatment in Ontario.The purpose was to examine patient and visit characteristics associated with YVM responses. Methods: YVM was administered to eligible patients (n=8,704) at 14 centres in 2017.Respondents answered items on a five-point Likert scale (4 or 5 = positive response). A multivariable logistic regression (MLR) was undertaken for each YVM item.Variables (reference group) included: disease site (heamatology), age group (65+), sex (female), rurality (urban), last visit type (consult), income quintile(highest) and immigration tercile (lowest). Significant results ( p&lt;.05) vary by MLR model. Therefore a p-value range is provided for all significant variables for all MLR models. Results: Patients were more likely to have a less positive experience if they had central nervous system ( p =.000-.013), gastrointestinal ( p =.004-.026), head and neck ( p =.002-.025), or lung cancer ( p =.017-.049); were between the ages of 18-39 years ( p = &lt;.0001-.048); were female ( p =.0001-.022); received chemotherapy( p =.0001-.047); lived in a rural location ( p =.042); from a mid-( p =.027-.045) and mid-high income quartile ( p =.021); and in the high- ( p =.002-.043) and middle-immigrant terciles ( p =.028-.047), when compared to the reference group. Patient were more likely to have a more positive experience if they had skin cancer ( p =.004-.032); were between the ages of 40-64 years ( p =.003-.033); receiving radiation ( p =.0001-.041) or a minor procedure ( p =.015); and were from the mid-low ( p =.003-.042) and low income quartile ( p =.001-.032), when compared to the reference group. Conclusions: The cancer patient experience varies by patient and visit characteristics. Future initiatives should examine these characteristics to better understand their populations to create a more tailored approaches to cancer care.
Is There an Increase in Sickle Cell Related Events Among the Adult Belgian Population?
Authors: Phu-Quoc Le, Beatrice Gulbis, Laurence Dedeken, Laurence Rozen, Christiane Vermylen, Anna Vanderfaeillie, Catherine Heijmans, Christine Devalck, Fleur Samantha Benghiat, Andre Efira, Marie-Françoise Dresse, Alina Ferster
Journal: Blood (2018)
Compartment-Specific Bioluminescence Imaging (CS-BLI): A High-Throughput Approach To Identify Novel Anti-Neoplastic Therapies That Overcome the Protection of Stromal Cells.
Authors: Douglas W. McMillin, Joseph M. Negri, Patrick Hayden, Ellen Weisberg, Steffen Klippel, Robert Schlossman, Nikhil C. Munshi, Nicholas Mitsiades, Paul G. Richardson, Kenneth C. Anderson, Constantine S. Mitsiades
Journal: Blood (2007)
Abstract 812: Mechanisms of Sinus Node Dysfunction and Chronotropic Incompetence in Rats with Heart Failure and Preserved Ejection Fraction
Authors: Thassio Mesquita, Jae H Cho, Rui Zhang, Joshua I Goldhaber, Eduardo Marbán, Eugenio Cingolani
Journal: Circulation Research (2019)

Introduction: Chronotropic incompetence is a common feature in patients afflicted by heart failure with preserved ejection fraction (HFpEF). However, the specific mechanisms remain unknown. Aim: To probe the mechanisms of chronotropic incompetence in HFpEF. Methods: Dahl salt-sensitive rats were fed high-salt diet (8% NaCl). Rats fed normal-salt diet (0.3% NaCl) served as controls. Echocardiography was used to confirm the development of diastolic dysfunction and preserved EF. Telemetry devices were implanted and treadmill exercise tests were performed to assess heart rate response to exercise. Sinus node recovery time (SNRT) was measured in vivo, and ex vivo optical mapping was performed in isolated sinoatrial node (SAN) tissue to measure heart rate response to isoproterenol. Results: HFpEF rats showed decreased E/A ratio (17%, p&lt;0.05) and increased E/E’ ratio (40%, p&lt;0.05) compared to controls, indicative of diastolic dysfunction, while EF remained unchanged in both groups. Resting mean blood pressure was elevated in HFpEF rats compared to controls (75%, p&lt;0.05). HFpEF rats exhibited low chronotropic response to maximal exercise, in association with prolonged cSNRT (46%, p&lt;0.05), indicative of abnormal SAN function. Despite unchanged baseline heart rate, ex vivo high-resolution optical mapping in isolated SAN tissue revealed delayed slow diastolic depolarization of spontaneous action potentials underlying the lower β-AR responsiveness, as well as slowed conduction (in association with histologically-evident increases in SA fibrosis). Next-generation RNA sequencing revealed that SAN from HFpEF rats shows numerous changes in transcripts associated with ion channels, protein kinases, and tissue remodeling. At the single SAN cell level, HFpEF rats showed decreased abundance of L-type Ca 2+ channels (Ca v 1.3, 55%) and hyperpolarization-activated "pacemaker" channels (HCN4, 67%) by western blot; such protein changes were associated with remarkable reductions of both currents. Conclusions: Chronotropic incompetence in HFpEF is due, in large measure, to intrinsic abnormalities of the SAN. Among these, a depressed membrane “clock” features prominently in the underlying mechanism.
Host Tissue PD-1 Pathway Contribute To Murine Chronic Graft-Versus-Host Disease Via Th1+Th17+ Cells
Authors: Hideaki Fujiwara, Yoshinobu Maeda, Koichiro Kobayashi, Hisakazu Nishimori, Ken-ichi Matsuoka, Miyuki Azuma, Hideo Yagita, Lieping Chen, Mitsune Tanimoto
Journal: Blood (2013)
Haploidentical transplantation in high‐risk pediatric leukemia: A retrospective comparative analysis on behalf of the Spanish working Group for bone marrow transplantation in children (GETMON) and the Spanish Grupo for hematopoietic transplantation (GETH)
Authors: Antonio Pérez‐Martínez, Cristina Ferreras, Antonia Pascual, Marta Gonzalez‐Vicent, Laura Alonso, Isabel Badell, José María Fernández Navarro, Alexandra Regueiro, Mercedes Plaza, Jose María Pérez Hurtado, Ana Benito, Cristina Beléndez, José Miguel Couselo, José Luis Fuster, Mariana Díaz‐Almirón, David Bueno, Yasmina Mozo, Julia Marsal, Alicia Gómez López, Luisa Sisinni, Cristina Díaz de Heredia, Miguel Ángel Díaz
Journal: American Journal of Hematology (2019)

A total of 192 pediatric patients, median age 8.6 years, with high-risk hematological malignancies, underwent haploidentical stem cell transplantation (haplo-HSCT) using post-transplantation cyclophosphamide (PT-Cy), or ex vivo T cell-depleted (TCD) graft platforms, from January 1999 to December 2016 in 10 centers in Spain. Some 41 patients received an unmanipulated graft followed by PT-Cy for graft-vs-host disease (GvHD) prophylaxis. A total of 151 patients were transplanted with CD3-depleted peripheral blood stem cells (PBSCs) by either CD34+ selection, CD3+ CD19+ depletion, TCRαβ+ CD19+ depletion or CD45RA+ depletion, added to CD34+ selection for GvHD prophylaxis. The PBSCs were the only source in patients following ex vivo TCD haplo-HSCT; bone marrow was the source in 9 of 41 patients following PT-CY haplo-HSCT. Engraftment was achieved in 91.3% of cases. A donor younger than 30 years, and the development of chronic GvHD were positive factors influencing survival, whereas positive minimal residual disease (MRD) before transplant and lymphoid disease were negative factors. The probability of relapse increased with lymphoid malignancies, a donor killer-cell immunoglobulin-like receptor (KIR) haplotype A and positive MRD pretransplant. No difference was found in overall survival, disease-free survival or relapse incidence between the two platforms. Relapse is still of concern in both platforms, and it should be the focus of future efforts. In conclusion, both platforms for haplo-HSCT were effective and could be utilized depending on the comfort level of the center.