tbuckley/cabot-search huggingface dataset:
Improving documentation of pain and constipation management within the cancer center of a large urban academic hospital.
Authors: Iloabueke Gabriel Chineke, Marjorie Adams Curry, Giselle Dutcher, Steve Power, Leon Bernal-Mizrachi
Journal: Journal of Clinical Oncology (2019)

192 Background: Pain and constipation are common among patients with cancer and remain inadequately controlled in many. Quality Oncology Practice Initiative (QOPI) assessment of pain and constipation at the Georgia Cancer Center for Excellence at Grady Health System identified documentation to be below benchmark levels. A quality improvement initiative to improve pain and constipation management was conducted. Methods: Given the low baseline documentation rates for pain (60%) and constipation (20%), we aimed for a 20-percentage point increase within one year. Based on cause and effect analysis and questionnaires to providers, our multidisciplinary team developed a new provider note template to integrate nurse’s assessment of pain and constipation into the provider’s documentation. A new order panel was developed in the electronic medical record (EPIC) to link appropriate orders with the pain and constipation plan. Results: Integrating the initial nursing assessment into the provider note template increased pain score documentation from 66.7% to 100%, P &lt; 0.01 and pain management plan from 65.3% to 86.4%, P = 0.06. Similarly, constipation assessment documentation improved from 20.4% to 100%, P &lt; 0.01 and a documented constipation plan improved accordingly from 11.2% to 29.1%, P &lt; 0.01. As a result of this intervention, pain control at the 3rd clinic visit improved from 61.5% to 86.8%, P &lt; 0.01. Emergency room visits related to pain and constipation decreased (16.2% to 14.9%, P = 0.19) and hospitalizations marginally increased (1.6% to 3.6%) during the study period. Conclusions: A standardized visit template and mandated assessment of pain and constipation exceeded the goal for improvement in documentation and positively impacted outcomes.
Abstract 330: A HaloTag-TEV Genetic Cassette for Mechanically Probing Native Titin
Authors: Jaime Andrés Rivas-Pardo, Yong Li, Zsolt Mártonfalvi, Rafael Tapia-Rojo, Andreas Unger, Ángel Fernández-Trasancos, Elías Herrero-Galán, Diana Velázquez-Carreras, Wolfgang A Linke, Julio M Fernández, Jorge Alegre-Cebollada
Journal: Circulation Research (2019)

Single-molecule methods using recombinant proteins have generated transformative hypotheses on how mechanical forces interact with titin in the sarcomere, enabling muscle contraction. However, testing these mechanical hypotheses on native titin in its natural environment has remained inaccessible to conventional genetics, biophysics and molecular biology tools. To overcome these limitations, here we demonstrate a genetically engineered knock-in mouse model carrying a HaloTag-TEV insertion in titin. Using our system, we have specifically severed the titin filament by digestion with TEV protease, and found that the response of muscle fibers to length changes requires mechanical transduction through titin’s intact polypeptide chain. HaloTag-based covalent tethering has enabled directed examination of the dynamics of native titin under physiological forces using recently developed magnetic tweezers. At physiological pulling forces lower than 10 pN, titin domains are readily recruited to the unfolded state, and produce 41.5 zJ mechanical work during refolding. Our results support an active role of titin in muscle contraction in coordination with actomyosin motors.
Ex Vivo Expanded Multi-Specific Cytotoxic T Lymphocytes Derived From HIV+ Patients and HIV Negative Donors Using GMP Compliant Methodologies Recognize Multiple HIV Antigens and Suppress HIV Replication
Authors: Sharon Lam, Julia Marsh Sung, Conrad RY Cruz, Paul Castillo-Caro, Minh T. Ngo, Carolina Garrido, Joann Kuruc, Cliona M. Rooney, David Margolis, Catherine M. Bollard
Journal: Blood (2013)
Acral lentiginous melanoma: differences in survival compared with other subtypes
Authors: M.D. Howard, C. Xie, E. Wee, R. Wolfe, C.A. McLean, J.W. Kelly, Y. Pan
Journal: British Journal of Dermatology (2019)

Dear editor, acral lentiginous melanoma (ALM) is typically diagnosed at an advanced stage which may be due its unique presentation 1 .Studies have evaluated whether the ALM subtype is an independent prognostic factor with conflicting results 2, 3 .Previous reports have been limited by small numbers and lacked adjustment for confounders [1][2][3] .Therefore, the aim of this study was to compare melanoma specific survival (MSS) of ALM with other subtypes.Institutional ethics approval was obtained for this cohort study.All invasive cutaneous primary melanoma cases reviewed at the Victorian Melanoma Service from 1994 until January 2016 underwent independent pathology review by an expert melanoma dermatopathologist.Survival information was obtained by linkage with the Victorian Cancer Registry.For patients with multiple melanomas, the case with the greatest thickness was retained.After exclusion of insitu cases (n=1329), non-registry linked cases (n= 317), unknown thickness (n= 44), and multiple melanomas (n= 334), 2951 invasive superficial spreading, acral lentiginous and nodular melanoma cases were available for analysis.
Detection of ADAMTS13 Autoantibodies and Elevated ADAMTS13/fXI Complex in Lupus Anticoagulant Positive Plasmas Suggest a Potential Role for ADAMTS13 in Antiphospholipid Syndrome.
Authors: Enriqueta R. Guinto, Ellyn Ercolano, Nicholas Grafos, Hugh J.L. Fryer, Clare Santulli, Jeffrey S. Dlott, Maryellen Belter, Robert S. Greenfield
Journal: Blood (2007)
Data Mining of Hematopoietic Stem Cell Microarray Studies Reveals a Novel Stem Cell Gene Expression Signature and Demonstrates Feasibility of Integrating Data from Different Labs and Different Microarray Platforms.
Authors: D. Sohal, A. Yeatts, K. Ye, A. Pellagatti, L. Zhou, P. Pahanish, J. Mariadason, A. Melnick, J. Greally, J. Boultwood, A. Verma
Journal: Blood (2007)
A PROM pilot in GI oncology clinic: Outcomes and lessons in real-world implementation.
Authors: Brian Halbert, Jim Doolin, Noah Xavier Tocci, Jessica A. Zerillo
Journal: Journal of Clinical Oncology (2019)

202 Background: Patient reported outcome measures (PROM) can prolong survival, improve quality of life and reduce ED visits. However, implementation of PROM into practice is challenging. We present the results of a PROM pilot in a tertiary GI oncology clinic. Methods: We recruited a convenience sample of 20 patients undergoing infusional chemotherapy. Patients were English speaking and &gt; 18 years old. We developed a PROM instrument targeting pain, nausea, diarrhea, constipation and fever symptoms in a third party secure online application. Symptoms were scored by frequency and severity on a 5-point Likert scale. The survey was distributed weekly to patients via the patient portal from March to April 2019. Survey results were monitored in real-time. Clinical teams were notified for any symptom score of 4 or 5, increase by 2 or more points between weeks, or self-identified concern. We conducted telephone interviews of non-responders halfway through the pilot to assess reasons for non-response. Results: The mean age was 59 years. Most were female (55%) and self-identified as white (75%). Colorectal (45%) and pancreatic (40%) cancer were the most common cancer types. Most (80%) had metastatic disease and FOLFOX (45%) was the most common regimen. Of the 121 weekly surveys sent, we received 40 responses (33%). Individual response rates ranged from 0% to 100% with a median rate of 25%. Of the 40 responses, 24 (60%) resulted in a clinical trigger. Pain was the most common trigger (n = 15; 63%) followed by self-identified concern (n = 9; 38%). Five triggers resulted in change in management; recommendation of an OTC medication was the most common intervention. There were 6 ED visits or hospitalizations among 5 patients. Of 9 non-responding patients, 4 reported not seeing the e-mail and 3 reported illness as the reason for non-response. All reported continued enthusiasm for the project. Conclusions: Despite known benefits, successful implementation of PROM remains challenging. We found difficulties with automated integration into the electronic medical record and patient response rates. These factors must be addressed to allow a successful PROM program. Despite these limitations, significant enthusiasm remains for the future of PROM.
Amplification of the ABL Gene in T-Cell Acute Lymphoblastic Leukemia (T-ALL).
Authors: Paolo Bernasconi, Silvia Calatroni, Ilaria Giardini, Alessandro Inzoli, Paola Maria Cavigliano, Marina Boni, Enrico Motta, Barbara Rocca, Maurizio Grassi, Clara Bianchessi, Rita Zappatore, Jessica Quarna, Marilena Caresana, Cesare Astori, Enrico Bobbio Pallavicini, Mario Lazzarino
Journal: Blood (2004)
Association of Occupational Exposure to Disinfectants With Incidence of Chronic Obstructive Pulmonary Disease Among US Female Nurses
Authors: Orianne Dumas, Raphaëlle Varraso, Krislyn M. Boggs, Catherine Quinot, Jan-Paul Zock, Paul K. Henneberger, Frank E. Speizer, Nicole Le Moual, Carlos A. Camargo
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Exposure to disinfectants in health care workers has been associated with respiratory health outcomes, including asthma. Despite the biological plausibility of an association between disinfectants (irritant chemicals) and risk of chronic obstructive pulmonary disease (COPD), available data are sparse. <h3>Objective</h3> To investigate the association between exposure to disinfectants and COPD incidence in a large cohort of US female nurses. <h3>Design, Setting, and Participants</h3> The Nurses’ Health Study II is a US prospective cohort study of 116 429 female registered nurses from 14 US states who were enrolled in 1989 and followed up through questionnaires every 2 years since. The present study included women who were still in a nursing job and had no history of COPD in 2009, and used data from the 2009 through 2015 questionnaires. Clean and complete data used for this analysis were available in July 2018, and analyses were conducted from September 2018 through August 2019. <h3>Exposures</h3> Occupational exposure to disinfectants, evaluated by questionnaire and a job-task-exposure matrix (JTEM). <h3>Main Outcomes and Measures</h3> Incident physician-diagnosed COPD evaluated by questionnaire. <h3>Results</h3> Among the 73 262 women included in the analyses, mean (SD) age at baseline was 54.7 (4.6) years and 70 311 (96.0%) were white, 1235 (1.7%) black, and 1716 (2.3%) other; and 1345 (1.8%) Hispanic, and 71 917 (98.2%) non-Hispanic. Based on 368 145 person-years of follow-up, 582 nurses reported incident physician-diagnosed COPD. Weekly use of disinfectants to clean surfaces only (16 786 [22.9%] of participants exposed) and to clean medical instruments (13 899 [19.0%] exposed) was associated with COPD incidence, with adjusted hazard ratios of 1.38 (95% CI, 1.13-1.68) for cleaning surfaces only and 1.31 (95% CI, 1.07-1.61) for cleaning medical instruments after adjustment for age, smoking (pack-years), race, ethnicity, and body mass index. High-level exposure, evaluated by the JTEM, to several specific disinfectants (ie, glutaraldehyde, bleach, hydrogen peroxide, alcohol, and quaternary ammonium compounds) was significantly associated with COPD incidence, with adjusted hazard ratios ranging from 1.25 (95% CI, 1.04-1.51) to 1.36 (95% CI, 1.13-1.64). Associations were not modified by smoking or asthma status (<i>P</i>for interaction &gt; .15). <h3>Conclusions and Relevance</h3> These longitudinal results suggest that regular use of chemical disinfectants among nurses may be a risk factor for developing COPD. If future studies confirm these results, exposure-reduction strategies that are compatible with infection control in health care settings should be developed.
Abstract 434: Acidifying Nanoparticle Upregulates Autophagy and Enhances Cardiomyocyte Survival after Chemotherapy
Authors: Zehedina Khatun, Lin Meng, Gregory Martin, Tanjheela Jahan, Lan Wei, Hushan Yuan, Lee Josephson, Choukri Mekkaoui, David E Sosnovik, Robert M Blanton, Howard H Chen
Journal: Circulation Research (2019)

Introduction: Chemotherapy-induced cardiotoxicity remains prevalent and deadly, with no effective therapy to slow the progression to irreversible heart failure, which in the case of doxorubicin (Dox) can reach 50% mortality. Dox impact on cardiomyocytes (CMs) is multifocal, including oxidative stress, lysosome alkalinization, and apoptosis. PLGAs, poly(DL-lactide-co-glycolide), are FDA-approved polymers, form defined nanoparticles (NPs). We hypothesize that PLGA NPs target the lysosomal compartments, restore lysosomal acidity after Dox, and confer cardioprotective effects. Methods: We synthesized fluorescent PLGA NPs by click chemistry. In H9C2 myocytes exposed to 1-5 μM of Dox +/- 1 mg/ml of PLGA, we measured cell viability (MTT), lysosomal pH (OG-514), mitochondrial membrane potential (JC-1), and autophagy proteins (western blot). We further co-injected C57Bl6 mice with PLGA (10 mg/kg, i.v.) and Dox (15 mg/kg, i.p.), to image apoptosis (Annexin) and autophagy (cathepsin-activatable autophagy probe, ADN, unpublished) after 24 hrs, or 4 mg/kg Dox weekly, 5x, i.p. and echo after 3-4 weeks. Results: PLGA NPs formulated are of controlled size and valency, emits near-infrared fluorescence (Fig. A). In H9C2s, PLGA significantly improved survival after Dox (Fig. B), acidified lysosomes (Fig. C), did not impact cell energetics (Fig. D), and further restored autophagic flux (Fig. E). Imaging in Dox mice revealed significant apoptosis reduction and autophagy activation (Fig. F-H), and cardiac function recovery (Fig. I). Conclusions: PLGA NPs may represent a novel class of cardioprotective therapeutics of early chemotherapy stress, and with translational potential.
Inactivation of Stage-Specific B-Cell Commitment Genes Generates Distinct Molecular Subtypes of BCR-ABL1 Lymphoblastic Leukemia
Authors: Jaeseung C. Kim, Michelle Chan-Seng-Yue, Gavin W. Wilson, Andrea Arruda, Karen Ng, Olga I. Gan, Stephanie M. Dobson, Paul M. Krzyzanowski, Johann K. Hitzler, Anne Tierens, John E. Dick, Mark D. Minden, John D. McPherson, Faiyaz Notta
Journal: Blood (2018)
Human Telomerase Reverse Transcriptase-Specific T-Cell Receptor Gene Transfer Redirects T-Lymphocytes to Exert Effective Antitumor Reactivity Against Adult T-Cell Leukemia,
Authors: Yukihiro Miyazaki, Hiroshi Fujiwara, Toshiki Ochi, Hiroaki Asai, Kozo Nagai, Takashi Ishida, Sachiko Okamoto, Junichi Mineno, Kiyotaka Kuzushima, Hiroshi Shiku, Masaki Yasukawa
Journal: Blood (2011)
Abstract 725: A Transcriptional Basis for Neonatal Heart Regeneration at Single Cell Resolution
Authors: Zhaoning Wang, Miao Cui, Akansha Shah, Wei Tan, Ning Liu, Rhonda Bassel-Duby, Eric N Olson
Journal: Circulation Research (2019)

The adult mammalian heart has limited capacity for regeneration following injury, whereas the neonatal heart can readily regenerate within a short period after birth. Deciphering the molecular underpinnings of neonatal heart regeneration and the blockade to regeneration in later life may provide novel insights for heart repair. Neonatal heart regeneration is orchestrated by multiple cell types including cardiac resident cells and immune cells that infiltrate the heart after injury. To systematically elucidate the transcriptional response after injury at cellular level during heart regeneration, we performed single cell RNA-sequencing on hearts at various time points post P1 or P8 myocardial infarction injury, and coupled that with bulk tissue RNA-sequencing data collected at the same time points. This integrated approach provides detailed transcriptome landscape and dynamics during heart regeneration at single cell resolution. We further depict a ligand-receptor interaction network that potentially reveal cellular signaling and cell-cell cross-talks during heart regeneration in cell autonomous and non-autonomous manners. Furthermore, to uncover the transcriptional dynamics in a single cardiomyocyte (CM), which was technically challenging due to incompatibility of CM diameter with Drop-Seq platforms, we performed single nucleus RNA-sequencing for CM population, and identified a subset of CMs in the regenerative hearts with unique molecular properties. Taken together, our data provide , and suggest numerous inroads that might be therapeutically manipulated to enhance cardiac function in response to injury.
The mitochondrial permeability transition pore in cell death: A promising drug binding bioarchitecture
Authors: Salvatore Nesci
Journal: Medicinal Research Reviews (2019)

Abstract Bioenergetic failure often features programmed cell death involved in some severe pathologies. When the cell is fated to die, the inner mitochondrial membrane becomes permeable to ions and solutes, due to the formation and opening of a channel known as mitochondrial permeability transition pore (mPTP). Up to now, the still‐elusive mPTP structure and mechanism prevented any attempt to identify/design drugs to rule its formation and limit cell death. Latest advances, which strongly suggest that the F 1 F O ‐ATPase can coincide with the mPTP, open new perspectives in therapy. Compounds targeting and inhibiting cyclophilin D, a known mPTP promoter, could be exploited to block mPTP formation. Moreover, if the mPTP‐F 1 F O ‐ATPase connection will be consolidated, selected F 1 F O ‐ATPase inhibitors could represent novel therapeutic options to attenuate mPTP‐related diseases by directly acting on mPTP molecular mechanism. This intriguing perspective, which raises new hopes to counteract mPTP‐related diseases, stimulates further studies to clarify the mPTP architecture and mechanism.
Nonmyeloablative Allogeneic Transplantation (NMT) for Relapsed Follicular Lymphoma (FL): Continuous Complete Remission with Longer Follow-Up.
Authors: Issa F. Khouri, Rima M. Saliba, Martin Korbling, Chitra Hosing, Luis Fayad, Ming S. Lee, Felipe Samaniego, Barry I. Samuels, Daniel Couriel, Fredrick Hagemeister, Peter McLaughlin, Richard E. Champlin
Journal: Blood (2007)
Tailoring implementation for a cancer self-management support intervention for patients starting chemotherapy.
Authors: Ryan Lawrence Kirkby, Doris Howell, Melanie Lynn Powis, Heidi Amernic, Lesley Moody, Mary Ann O'Brien, Sara Rask, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2019)

287 Background: Multiple implementation strategies are described in the literature; however, there is limited consensus on how to best tailor implementation to organizational and clinician readiness. We undertook a mixed-methods evaluation to inform tailored implementation of self-management support (SMS) in ambulatory cancer care as the first phase of a pilot randomized trial of the intervention in patients starting chemotherapy. Methods: Validated surveys, focus groups and interviews were undertaken with key stakeholders (oncologists, nurses, allied health, and administrative leaders) in the lung, colorectal and lymphoma disease site groups at 3 regional cancer centres in Ontario, Canada. Median responses to individual survey questions were classified as an enabler, barrier or neutral based on predetermined cut-offs. Enablers and barriers were triangulated with qualitative data and mapped to the Consolidated Framework for Implementation Research domains. Implementation strategies to address barriers were identified using the Expert Recommendations for Implementing Change tool. Results: Survey respondents represented all stakeholder groups (n = 78; respondent rate = 50%). Minimal variation was noted across stakeholders and centres. Overall, respondents held positive beliefs about the value of SMS, were familiar with the principles of SMS and felt there was a tangible fit among the intervention, individual beliefs, and existing workflows. Suboptimal communication networks and access to information about the adoption of SMS, as well as a lack of organizational commitment to implementing the intervention were identified as key implementation barriers. Qualitative data reinforced quantitative findings, namely that stakeholders value SMS but were unsure if it would translate into reduced treatment toxicities. 46 implementation strategies were identified based on perceived barriers, of which 28 (61%) were common to all 3 centres. Conclusions: Stakeholders at cancer centres acknowledged that SMS is valuable, but potential barriers to integration of SMS into routine ambulatory practice exist. The impact of the tailored implementation plans will be evaluated as part of the trial.
Using Lean methodology to improve the time to antibiotics in oncology patients on chemotherapy who present to the ED with neutropenic fever.
Authors: Brian J. Byrne, Frederick Bailey, Pat Montanaro, Patricia Anne DeFusco
Journal: Journal of Clinical Oncology (2019)

31 Background: Neutropenic fever is a medical emergency. Delays in treatment can lead to increase in morbidity, mortality, and increase length of stay. The American Society of Clinical Oncology currently recommends that antibiotics be prescribed within 60 minutes of triage. Literature review shows through a multidisciplinary effort involving the ED, lab, oncology, and pharmacy significant improvement in time to antibiotics can be achieved. Since many patients with neutropenic fever present with sepsis, these guidelines also will need to be followed. Methods: Three PDSA cycles were conducted. The first involved education of the ED staff on the importance of treating neutropenic fever and using the correct antibiotic. The second PDSA cycle involved the laboratory and the calling of critical white counts and low neutrophil counts. The third PDSA involves patient education on the importance of temperature monitoring and reporting they are on chemotherapy to ED staff. Results: Baseline data show only 33% of patients receive the correct antibiotic and the average time to administration is 3 hours and 41 minutes. Results of the quality improvement project show a substantial improvement in time to antibiotic administration to 1 hour 58 minutes and an increase in the percentage of patients who receive the correct antibiotic. The time from the specimen received in the lab until critical called also improved from 1 hour 14 minutes to 18.5 minutes. Conclusions: This quality improvement led to a significant improvement in time to correct antibiotics, but several additional steps need to be taken to meet ASCO guidelines. [Table: see text]
Preliminary Results of a Phase 2 Study of PD 0332991 in Combination with Bortezomib and Dexamethasone in Patients with Relapsed and Refractory Multiple Myeloma
Authors: Ruben Niesvizky, Luciano J Costa, Nisreen A. Haideri, Georg Hess, Seema Singhal, Ivan Spicka, Edward A. Stadtmauer, Ashraf Z. Badros, Marc S Raab, John L Jakubczak, Sindy T. Kim, Sophia Randolph, Scott A Ely, Selina Chen-Kiang
Journal: Blood (2011)
US paediatric oncologists are forced to prioritise patients for vincristine treatment as supplies run short
Authors: Owen Dyer
Journal: BMJ (2019)

Vincristine, a cornerstone of paediatric cancer treatment, is in critically short supply across the United States after one of the last two makers on the US market, Teva Pharmaceutical Industries, stopped production.

“This is a nightmare situation,” paediatric oncologist Yoram Unguru, of the Herman and Walter Samuelson Children’s Hospital in Baltimore, told the New York Times . “Childhood cancer specialists must now begin the task of prioritising their limited supply of vincristine among equally deserving children.”

Unguru added, “Vincristine is our water. It’s our bread and butter. I can’t think of a disease in childhood cancer that doesn’t use vincristine. There is no substitute that can be recommended. You either have to skip a dose or give a …
FISH Analysis of IgH Rearrangement by 4 Kinds of Probes Involving IgH Genes in Multiple Myeloma: Improved Sensitivity for the Detection by Use of IGH Break-Apart Probe.
Authors: Hye Yoon Chung, Miyoung Kim, Cha Ja See, Hyun Jung Min, Sung-Soo Yoon, Han Ik Cho, Dong Soon Lee
Journal: Blood (2007)