tbuckley/cabot-search huggingface dataset:
Implementing an early discharge initiative for patients receiving high-dose methotrexate.
Authors: Adam Binder, Samantha Burdette, Patricia Galanis, Katlin Birchmeier, Nathan Handley, Maria Piddoubny
Journal: Journal of Clinical Oncology (2019)

90 Background: Over 70% of patients are hospitalized in the first year after a cancer diagnosis. While some admissions are unplanned and potentially preventable, many are planned admissions for intensive chemotherapy. High Dose Methotrexate (HD-MTX) is commonly used for the treatment of osteosarcoma or CNS involvement in lymphoproliferative neoplasms. It is given in the inpatient setting due to monitoring requirements after administration. We postulated that changing discharge criteria for HD-MTX from 0.05 µmol/L to ≤0.1 µmol/L would be feasible and safe, and would reduce length of stay (LOS) for patients receiving HD-MTX. Cost savings were also calculated. Methods: Following an assessment of drivers of LOS amongst patients receiving HD-MTX, we identified discharge criteria as an actionable factor. We developed a workflow to discharge patients with 3 days of oral leucovorin and sodium bicarbonate when MTX level reached ≤0.1 µmol/L. Patient demographics, chemotherapy regimen, cycle, dose, and LOS data were collected for a 7 month period before and a 4 month period after the intervention. Cost savings were estimated based on the daily cost of a hospital bed at the institution. Results: Mean LOS for the pre-intervention and post-intervention group was 4.84 days (n=49) and 3.67 days (n=42), respectively (p=0.007). This resulted in a 24.4% reduction in length of stay. Average reduction in LOS of 1.17 days resulted in a decrease in cost of $1,828.73 per admission, with a 4 months savings of $76, 806.56 and projected annualized savings of $230,419.67. No patient experienced complications because of change in discharge criteria. Conclusions: Liberalizing discharge criteria for HD-MTX is feasible, safe, and cost-effective. Further efforts to reduce LOS for elective chemotherapy admissions or safely transition some of these complex regimens to the home setting are currently underway at our institution.
Implementation of a pregnancy screening protocol prior to chemotherapy for women of childbearing potential.
Authors: Christian Eastlake, Kate Jeffers
Journal: Journal of Clinical Oncology (2019)

246 Background: Many cancer therapies currently available are teratogenic in nature. Several patients cared for within our community ambulatory oncology infusion center are women of childbearing potential (WOCP). Pregnancy testing of these women within our oncology infusion center was sporadic at best. There currently are no standardized guidelines related to pregnancy testing of these women. Methods: A retrospective chart analysis of WOCP receiving chemotherapy was done to determine baseline pregnancy screening rates. Subsequently a protocol was developed in which WOCP was defined as women under 50 years of age, without a history of hysterectomy or tubal ligation. The nurse-driven protocol allowed the infusion nursing staff to order a pregnancy screen to be done within the infusion center if testing had not already taken place within 48 hours of initiation of treatment. Following protocol implementation a retrospective chart analysis was performed to re-examine screening rates. Results: Utilizing patients with an active treatment plan within a one month time period, retrospective analysis of pregnancy screening prior to initiation of chemotherapy was performed. Baseline pregnancy screening rate was 21%. Point of care pregnancy equipment was obtained and nursing staff was educated on the protocol to include a medical delegation. Post-implementation chart analysis of WOCP initiating chemotherapy within a six-week timeframe resulted in improved pregnancy screening to 57% compliance. Continued education and clarification of the protocol was provided to the nurses in an effort to further improve compliance. Conclusions: Lack of standard guidelines regarding pregnancy screening of WOCP led to the development and implementation of a protocol for pregnancy screening for this at-risk population. Medical delegation allowed nursing to initiate the screening for these patients allowing for improvements in the safety and quality of patient care provided.
34-Year Single Center Observational Review of Ex-Vivo T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplants for Chronic Myeloid Leukemia
Authors: Philippa Woolley, David Slade, Richard Syzdlo, George Nasry Nesr, Simone Claudiani, Irene Caballes, Fiona Fernando, Jiri Pavlu, Renuka Palani, Edward Kanfer, Eduardo Olavarria, Dragana Milojkovic, Jane Apperley
Journal: Blood (2018)
Global Gene Expression Analysis Reveals Genotoxic Effect of Nrf2 Pharmacological Inhibitor Brusatol in Myeloid Leukemia Cells- a Promising Novel Anticancer Agent
Authors: Raveen Stephen Stallon Illangeswaran, Sreeja Karathedath, Bharathi M Rajamani, Poonkuzhali Balasubramanian
Journal: Blood (2018)
Abstract 886: Mitochondrial Stress Response by Lonp1 in Cardiac Function and Protection
Authors: Venkatesh Sundararajan, Mingming Tong, Erdene Baljinnyam, Anjaneyalu Murari, Peiyong Zhai, Edward Owusu-Ansah, Diego Fraidenraich, Junichi Sadoshima, Carolyn K Suzuki
Journal: Circulation Research (2019)

LonP1 is a mitochondrial protease that is crucial for maintaining cardiac mitochondrial homeostasis. We recently showed that LonP1 mediates cardioprotection during cardiac ischemia-reperfusion (I/R) by reducing oxidative stress and infarct size. We hypothesize that LonP1 promotes mitochondrial biogenesis during cardiac differentiation and development and protects the heart from oxidative injury by recalibrating bioenergetics. Here, we employ human induced pluripotent stem cells differentiated into cardiomyocytes (iPSC-CMs), rat neonatal ventricular myocytes (rNVMs), and mouse models with cardiac-specific LonP1 overexpression (LonTg) and heterozygous LonP1 knockout ( LONP1 +/- ). In iPSC-CMs, LonP1 is induced 4.8-fold at 39 vs. 12 days after differentiation. During the maturation of murine hearts, LonP1 is increased 4.6-fold at 3 months vs. during 1 day. Upregulation was also observed in rNVMs in which LonP1 is induced 5- fold after 5 days culturing, compared to 0 days. LonP1 induction in rNVMs is accompanied by substantial 2-fold upregulation of mitochondrial transcripts, MT-CYB and MT-COI. However, the levels of another mitochondrial matrix protease ClpP was not altered, suggesting that LonP1 specifically may play an important role during mitochondrial biogenesis and proteostasis in the heart. In vivo, LonTg protected the myocardium against ischemia-reperfusion (I/R) injury by preventing oxidative damage. In LonTg hearts, basal complex I activity was significantly (p&lt;0.05) reduced (Ntg-0.01 ± 0.001 vs. LonTg-0.0078 ± 0.001 mOD/min), as well as during I/R (Ntg-0.0139 ± 0.0005 vs LonTg-0.0102 ± 0.001 mOD/min) (n=3 each). However, no difference was observed in the complex I activity in LONP1 +/+ (0.0118 ± 0.0 mOD/min) and LONP1 +/- (0.0121 ± 0.0 mOD/min) mice (n=3 each). In addition, our preliminary native gel data of LonTg hearts shows a 40% reduction (n=1) in the levels of mitochondrial supercomplexes, compared to NTg hearts (n=4). Further studies are underway to explore the role of LonP1 during differentiation, and in response to mitochondrial cardiac stress. Together, our findings show a novel role of LonP1 in regulating cardiac function during mitochondrial biogenesis and in mitigating cardiac stress-induced injury.
Abstract 103: Single Cell Transcriptome Analyses Reveal Novel Targets for Therapeutic Neovascularisation by Resident Endothelial Cells in the Heart
Authors: Ziwen Li, Emmanouil G Solomonidis, Rodger Duffin, Ross Dobie, Marlene S Mahalhaes, Beth E Henderson, Pieter A Louwe, Gabriela D'Amico, Kairbaan M Hodivala-Dilke, Ajay M Shah, Nicholas L Mills, Benjamin D Simons, Gillian A Gray, Neil C Henderson, Andrew H Baker, Mairi Brittan
Journal: Circulation Research (2019)

Aims: A better understanding of the pathways that regulate regeneration of the coronary vasculature is important for future strategies to treat patients with heart disease. We investigated (i) the clonal dynamics of endothelial cells (EC) associated with neovascularization in the ischemic border region (ii) transcriptional signatures of regenerative EC in the ischemic heart using single cell RNA-sequencing (iii) the functional relevance of selected targets. Methods: MI was induced in ‘EC-Confetti’ mice by coronary artery ligation. EC clonal proliferation was quantified or hearts dissociated for scRNAseq. Immunofluorescence staining for targets identified by scRNAseq was performed on cardiac tissue from patients with ischemic heart disease. EC proliferation was assessed in vitro following siRNA gene silencing. Results: EC-Confetti mice express YFP, RFP, GFP, or CFP specifically in EC. Fluorophores are inherited by EC progeny following proliferation, allowing quantitative clonal analysis. Clonal proliferation was significantly increased in the infarct border at 7 days post-MI compared to healthy hearts ( P &lt;0.0001). Ten transcriptionally discrete EC clusters were defined following scRNAseq with 3 clusters predominantly composed of cells from the MI group, indicating their gene expression profiles may be relevant to neovasculogenic pathways. We selected plasmalemma vesicle associated protein (Plvap) for further study and confirmed EC-specific increased Plvap expression in ischemic border regions of human ( P =0.002) and mouse ( P =0.002) hearts, compared to healthy myocardium. siRNA gene silencing of Plvap significantly inhibited EC proliferation ( P = 0.0038), strong evidence that Plvap can directly modulate EC function. Conclusions: Generation of new blood vessels following ischemic injury in the mouse heart is predominantly mediated by clonal proliferation of resident EC. We present a gene expression atlas of resident cardiac EC, and the transcriptional hierarchy underpinning endogenous vascular repair following MI. This resource identifies novel targets, including Plvap, that may augment myocardial perfusion post-MI, and inform future design of strategies aimed at promoting vascular perfusion in ischemic heart disease.
Implementation of a geriatric oncology screening tool (G8) in an academic oncology practice serving a Hispanic-rich population.
Authors: Mary Salazar, Deborah James, Carolyn Welch, Jeremy Viles, Anand B. Karnad, Sukeshi Patel Arora
Journal: Journal of Clinical Oncology (2019)

87 Background: ASCO recommends utilization of the G8 screening tool to assist in predicting mortality, but there are limited data in Hispanic patients. Our practice utilizes the G8 to identify patients who may need additional support and/or treatment modifications to decrease risk of mortality. Therefore, we built the G8 in our Electronic Medical Record (EMR) with reflex to geriatric consultation in our Hispanic-rich patient population. Methods: This is an implementation study with a team-based approach to improve the utilization and increase geriatric oncology assessments in our practice. The G8 is a geriatric screening tool of eight questions (completion time: 3 to 5 minutes). If the score is &lt;/=14, a reflexive geriatric consultation box appears on the screen to recommend a referral to Geriatrics for a Comprehensive Geriatric Assessment (CGA). Nurses were empowered to complete the G8 on all new cancer patients 65+ years. Results: 215 patients had a G8 recorded in the EMR between August 2018 - March 2019. Providers completing: 10 (5%) MD/APP, 205 (95%) RNs. 119 patients were non-Hispanic, 96 were Hispanic. Of Hispanic patients, 74 (77%) spoke English, 5 (5%) spoke English and Spanish, 16 (17%) spoke Spanish, 1 (1%) spoke other. 205 patients (95.3%) were 65+ years. Average G8 score for all patients 65+ was 11.1. Of patients 65+, 169 patients (82%), scored &lt;/=14, indicating higher mortality risk. Conclusions: Integration of the G8 into our practice has been slow and steady. We believe this is partly due to lack of awareness of the benefit of the G8. Empowering nurses to complete the G8 has improved screening at our cancer center. To further improve awareness and utilization, we have initiated an interprofessional education lecture series regarding care of geriatric oncology patients, which provides nurses CNE. As we gather data on the reflex referrals to geriatricians for CGA, we will work on goals to increase MD/APP engagement. [Table: see text]
Abstract 924: The Role of Protein Kinase C Isoforms in Cardiomyocyte Hypertrophy
Authors: Lotta Pohjolainen, Reesha Solanki, Heikki Ruskoaho, Virpi Talman
Journal: Circulation Research (2019)

Background: Protein kinase C (PKC) has been linked to cardiomyocyte hypertrophy. However, the exact role of different PKC isoforms in mediating the hypertrophic response remains controversial and both classical and novel isoforms have been suggested to play a critical role. The aim of this study was to characterize the role of PKC isoforms in cardiomyocyte hypertrophy using pharmacological tools and high content screening (HCS). Methods: Neonatal rat ventricular cardiomyocytes (NRVCs) isolated from 1-3 days old Wistar rats and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) differentiated from iPS(IMR90)-4 line were exposed to endothelin-1 (ET-1) and PKC modulators for 48 h followed by fixing and immunofluorescence staining for nuclei, α-actinin and F-actin. Imaging and morphological analysis of thousands of cells were carried out using automated HCS platform. Results: NRVCs exposed to ET-1 (100 nM) or PKC agonists (HMI-1b11 at 10 μM or bryostatin-1 at 10 nM) or inhibitor of classical PKC isoforms, Gö6976 (1 μM), showed a hypertrophic phenotype measured by increased area and number of alpha-actinin and F-actin fibers in HCS. In contrast, inhibition of all PKC isoforms with Gö6983 (1 μM) attenuated ET-1 and PKC agonist-induced hypertrophy similarly to mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor U0126 (10 μM). In turn, these HCS parameters did not show ET-1 or PKC agonist -induced hypertrophy in hiPSC-CMs. However, qRT-PCR analysis of the expression of NPPA and NPPB genes showed hypertrophic responses to ET-1 and PKC agonists also in hiPSC-CMs. Conclusions: These results confirm the central role of PKC in cardiomyocyte hypertrophy and indicate that either classical PKC isoforms have a direct anti-hypertrophic role in cardiomyocytes or, when classical PKCs are inhibited, the balance is moved towards activation of novel isoforms, which mediate the hypertrophic response. Due to the morphological differences between NRVCs and hiPSC-CMs, similar phenotypic analysis readouts cannot be reliably applied to compare hypertrophic responses in these cell types. These findings may help in developing new drugs that target specific PKC isoforms to treat cardiac hypertrophy.
Evaluation of Hospital Admission Patterns in Children Receiving Treatment for Acute Lymphoblastic Leukemia: What Does a Typical Leukemia Experience Look like?
Authors: Allison Barz Leahy, Caitlin W Elgarten, Yimei Li, Yuan-Shung V. Huang, Brian T. Fisher, Dean Delp, Richard Aplenc, Kelly D Getz
Journal: Blood (2018)
Risk and Prognostic Factors of Extra-Nodal Hodgkin Lymphoma: Single Jordanian Center Experience
Authors: Tariq Zuheir Kewan, Deeb Jamil Zahran, Abdel-Hameed WASFI AL-Mistarehi, Hassan Awada, Valentina Giudice, Valeria Visconte, Mahmoud H Ayesh (Haj Yousef)
Journal: Blood (2018)
Lower Relapse and Better PFS Among Chemosensitive Patients Undergoing Allogeneic Transplantation By Haploidentical Compared With HLA-Identical DONOR: Results On A Cohort Of 94 Patients With Hodgkin’S Lymphoma
Authors: Luca Castagna, Roberto Crocchiolo, Stefania Bramanti, Sabine Furst, Barbara Sarina, Jean El Cheikh, Angela Granata, Raynier Devillier, Sylvain Garciaz, Reda Bouabdallah, Armando Santoro, Didier Blaise
Journal: Blood (2013)
"Ultrasensitive Reactive C-Protein As an Affordable Biomarker of Quantitative Expression of the BCR-ABL Transcript in Chronic Myeloid Leukemia. an Exploratory Study."
Authors: Luis Villela, Melani Otañez Arce, Carlos Best, Alicia Guzman, Elva Gabriela Estrada, Laura Rivera Mendoza, Juan Carlos Lopez Hernandez, Arianna Robles, David Gomez-Almaguer
Journal: Blood (2018)
Dietary Adherence in a Clinical Trial of a Nutritional and Behavioral Intervention
Authors: Philip Greenland
Journal: JAMA (2019)

Carmen Sayón-Orea, MD; Cristina Razquin, PhD; Mónica Bulló, PhD; Dolores Corella, PhD; Montserrat Fitó, MD; Dora Romaguera, PhD; Jesús Vioque, MD; Ángel M. Alonso-Gómez, MD; Julia Wärnberg, PhD; J. Alfredo Martínez, MD; Luís Serra-Majem, MD; Ramón Estruch, MD; Francisco J. Tinahones, MD; José Lapetra, MD; Xavier Pintó, MD; Josep A. Tur, PhD; José López-Miranda, MD; Aurora Bueno-Cavanillas, MD; Miguel Delgado-Rodríguez, MD; Pilar Matía-Martín, MD; Lidia Daimiel, PhD; Vicente Martín Sánchez, MD; Josep Vidal, MD; Clotilde Vázquez, MD; Emilio Ros, MD; Miguel Ruiz-Canela, PhD; José V. Sorlí, MD; Olga Castañer, MD; Miquel Fiol, MD; Eva M. Navarrete-Muñoz, PhD; Fernando Arós, MD; Enrique Gómez-Gracia, MD; M. Angeles Zulet, PhD; Almudena Sánchez-Villegas, PhD; Rosa Casas, PhD; Rosa Bernal-López, PhD; José M. Santos-Lozano, MD; Emili Corbella, PhD; Cristina Bouzas, PhD; Ana García-Arellano, MD; Josep Basora, MD; Eva M. Asensio, PhD; Helmut Schröder, PhD; Manuel Moñino, PhD; Manoli García de la Hera, MD; Lucas Tojal-Sierra, MD; Estefanía Toledo, MD; Andrés Díaz-López, PhD; Albert Goday, MD; Jordi Salas-Salvadó, MD; Miguel A. Martínez-González, MD
Early Deaths After Allogeneic Stem Cell Transplantation in Adult T Cell Leukemia/Lymphoma (ATLL) Patients - A Single Institute Retrospective Analysis
Authors: Shogo Takeuchi, Nobuaki Nakano, Ayumu Kubota, Yoshifusa Takatsuka, Mayumi Tokunaga, Takahiro Itoyama, Atae Utsunomiya, Kentarou Yonekura
Journal: Blood (2011)
Leaders responsible for sexist culture at BMA should consider quitting, says doctor
Authors: Abi Rimmer
Journal: BMJ (2019)

One of the doctors who raised the issue of sexism at the BMA has called for those responsible for the behaviour or for perpetuating it to consider leaving their posts to allow a culture change at the association.

The review, led by Daphne Romney QC, revealed a culture in which women (doctors and staff) at the BMA were bullied, undermined, and in some cases sexually harassed. It criticised the discriminatory culture at the BMA and the leadership for failing to call out bad behaviour.1

The review followed allegations of sexist remarks made to Zoe Norris and Katie Bramall-Stainer, senior representatives of the BMA GP committee, at the conference of UK local medical committees earlier this year.2 The allegations prompted other doctors, including Stephanie deGiorgio and Amy Small, to …
Abstract 777: Dual-Specificity Phosphatase 6 Deficiency Protects Against Intimal Hyperplasia After Arterial Injury
Authors: Shaw-Fang Yet
Journal: Circulation Research (2019)

Dysregulation of MAPK activation cascades has been implicated in various diseases. Dual-specificity phosphatases (DUSPs) are a subfamily of protein tyrosine phosphatases that dephosphorylate MAPKs and modulate critical signaling pathways. Studies have shown that DUSP6 plays an important role in the heart and diet-induced obesity. However, the role of DUSP6 in vascular disease is largely unclear. Our goal is to investigate whether DUSP6 has a role in occlusive vascular disease. To this end, we used a neointima formation model by denuding endothelium of mouse femoral arteries with a guide wire. We showed that DUSP6 was expressed at very low levels in the normal uninjured mouse arteries; however, DUSP6 expression was increased in the arterial wall of injured blood vessels, suggesting a potential role of DUSP6 in vascular disease. Compared with wild-type mice, DUSP6 deficiency reduced neointima formation 4 weeks after arterial injury in mice. BrdU incorporation assays revealed that lack of DUSP6 resulted in decreased smooth muscle cell (SMC) proliferation in the neointima and media 2 weeks after injury, indicating DUSP6 may promote SMC proliferation in response to injury. Indeed, overexpressing DUSP6 in primary SMCs increased cellular proliferation, similar to that exerted by inflammatory cytokine IL-1&amp;#946; while knocking down DUSP6 expression with siRNA abrogated IL-1&amp;#946;-induced SMC proliferation. Pathway analysis showed that IL-1&amp;#946;-induced ERK1/2 activation preceded DUSP6 induction in SMCs. Intriguingly, ERK1/2 inhibitor U0126 abolished IL-1&amp;#946;-mediated ERK1/2 activation, DUSP6 induction, and SMC proliferation. Taken together, our results indicate that DUSP6 induction promotes vascular remodeling under pathological conditions. DUSP6 might be a therapeutic target for preventing/treating occlusive vascular disease.
Myeloma-Induced Osteocyte Death Was Blunted By Proteasome Inhibitors Through The Modulation Of Autophagy
Authors: Denise Toscani, Carla Palumbo, Benedetta Dalla Palma, Marina Bolzoni, Marzia Ferretti, Paola Sena, Daniela Guasco, Eugenia Martella, Franco Aversa, Nicola Giuliani
Journal: Blood (2013)
The carbon footprint of the Chinese health-care system: an environmentally extended input–output and structural path analysis study
Authors: Rui Wu
Journal: The Lancet Planetary Health (2019)

BackgroundThe health sector plays an important part in adapting to climate change; however, the sector is also responsible for significant greenhouse gas (GHG) emissions. In high-income countries, the carbon footprints of health-care systems have been estimated to be 3–10% of the total national GHG emissions, but no in-depth investigation has been done for China. This study aims to examine the carbon footprint of the Chinese health-care system and identify emission hotspots.MethodsEnvironmentally extended input–output analysis and structural path analysis were used to assess the lifecycle GHG emissions of the Chinese health-care system. A satellite account of GHG emissions was constructed for 46 economic sectors in China using energy data from the National Bureau of Statistics based on the numbers reported by a large number of enterprises. Data on health expenditure for medical institutions, pharmaceuticals, construction, administration, and research were obtained from multiple Chinese official statistics yearbooks and the national input–output table.FindingsIn 2012, China spent CNY 2539 billion on health care, leading to emissions of 315 (68% CI 267–363) megatonnes CO2 equivalent. Health care accounted for 2·7% (68% CI 2·3–3·1) of China's total GHG emissions. The major contributors of GHG emissions in the health-care system were public hospitals (148 megatonnes [47%]), non-hospital purchased pharmaceuticals (56 megatonnes [18%]), and construction (46 megatonnes [15%]). In medical institutions, energy use for buildings and transport accounted for only 16% of the total carbon footprint, whereas 84% was embodied in the purchased goods and services.InterpretationChina has a much smaller health-care carbon footprint per capita than developed countries, such as the USA and Australia. However, its carbon emissions per unit of health expenditure are relatively high because of the expenditure structure and the carbon intensity of the country's entire economy. The results suggest the need for a nationwide carbon-efficient target for health care and use of low-carbon alternatives in making supply chain choices to achieve reductions in the carbon footprint.FundingNatural Science Foundation of China.
One-Mutation Model Can Explain Age Incidence in AML Carrying Nucleophosmin (NPM1) Mutations.
Authors: Arcangelo Liso, Filippo Castiglione, Antonio Cappuccio, Fabrizio Stracci, Christian Thiede, Gerhard Ehninger, Susanne Schnittger, Torsten Haferlach, Peter Valk, Bob Lowenberg, Massimo F. Martelli, Brunangelo Falini
Journal: Blood (2007)