tbuckley/cabot-search huggingface dataset:
Implementing a quality improvement curriculum for medical oncology residents: A pilot study at the Ottawa Hospital Cancer Centre.
Authors: Stephanie Yasmin Brule
Journal: Journal of Clinical Oncology (2019)

10540 Background: With increasing cancer care costs and demands in Canada, quality improvement (QI) efforts are urgently needed. Yet no formal QI education exists in the Canadian Medical Oncology setting. We created an Oncology-specific QI curriculum and sought to assess its feasibility and efficacy among Medical Oncology residents. Methods: In this prospective, pre-experimental pilot study using a pre-post curriculum design, Medical Oncology residents at The Ottawa Hospital Cancer Centre participated in a new QI curriculum. It consisted of four 2-hour sessions encompassing a combination of didactic and interactive learning. The primary measures were self-assessment of confidence in QI skills with the Self-Assessment Program (SAP) and objective assessment of QI knowledge with the revised QIKAT (QIKAT-R). The SAP and QIKAT-R were completed at baseline and post-curriculum. The primary outcome was feasibility of the educational approach. Results: Five Medical Oncology participated, while four (80%) completed the assessments at both timepoints. Self-assessment in the skills needed to execute a process improvement project improved with participation in the curriculum. Mean SAP scores improved from 19.6 pre-curriculum to 33.5 post-curriculum. SAP scores improved for each of the 10 quality improvement skills evaluated. Objective assessment using the QIKAT-R also improved post-curriculum, with a mean score of 17 pre-curriculum and 24 post-curriculum. Mean scores of each domain of “Aim, Measure, and Change” evaluated by the QIKAT-R improved. Conclusions: Self-assessed confidence and objective knowledge in QI concepts in Medical Oncology residents improved after participation in this Oncology-specific QI curriculum. Feasibility of this approach was demonstrated, and therefore a larger scale study will be implemented in the future.
Lung cancer prediction: Phase transitions and cell ratio factors
Authors: O. Kshivets
Journal: Journal of Clinical Oncology (2009)

e22170 Background: Search of precise prognostic factors for non-small lung cancer (LC) patients (LCP) was realized. Methods: In trial (1985–2008) the data of consecutive 490 LCP after complete resections R0 (age=56.7±8 years; m=439, f=51; tumor diameter: D=4.5±2.1 cm; pneumonectomies=206, lobectomies=284, combined procedures with resection of pericardium, atrium, aorta, VCS, carina, diaphragm, ribs=130; squamous=308, adenocarcinoma=147, large cell=35; T1=143, T2=217, T3=107, T4=23; N0=282, N1=115, N2=93; G1=114, G2=140, G3=236; early LC: LC till 2 cm in D with N0=58, invasive LC=432) was reviewed. Variables selected for 5-year survival (5YS) study were input levels of blood cell subpopulations, TNMG, D. Neural networks computing, Cox regression, clustering, structural equation modeling, Monte Carlo and bootstrap simulation were used to determine any significant regularity. Results: For total of 490 LCP overall life span (LS) was 1824±1304 days (median=1879) and real 5YS reached 62%, 10 years - 50.3%, 20 years - 45.3%. 304 LCP (LS=2597.3±1037 days) lived more than 5 years without LC progressing. 186 LCP (LS=559.8±383.1 days) died because of LC during first 5 years after surgery. 5YS of early LCP was significantly superior (100%) compared with invasive LCP (56.9%) (P=0.000 by log-rank test). 5YS of LCP with N0 was significantly better (78.4%) compared with LCP with N1–2 (39.9%) (P=0.000). Cox modeling displayed that 5YS significantly depended on: phase transition (PT) in terms of synergetics “early-invasive LC”, PT N0-N12, histology, G1–3, cell ratio factors: ratio between the total populations of leucocytes, lymphocytes, neutrophils and LC cells (P=0.000–0.044). Neural networks computing, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT “early-invasive LC”, (rank=1), PT N0-N12 (2), histology (3), G1–3 (4), T1–4 (5), ratio of lymphocytes/LC cells (6), healthy cells/LC cells (7), erythrocytes/LC cells (8), thrombocytes/LC cells (9), eosinophils/LC cells (10), neutrophils/LC cells (11). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; urea under ROC curve=1.0). Conclusions: 5YS of LCP after radical procedures depended on: 1) PT “early-invasive LC”; 2) PT N0-N12; 3) cell ratio factors; 4) LC characteristics. No significant financial relationships to disclose.
Role of Molecular Drivers in Coagulation By Integral Assessment in Primary Myelofibrosis Patients
Authors: Elizaveta Efremova, Olesya Matvienko, Natalya Korsakova, Mikhail Fominykh, Natalya Silina, Ludmila Papayan, Lyubov Polushkina, Ekaterina Motyko, Irina Martynkevich, Vasily Shuvaev, Sergei Voloshin
Journal: Blood (2018)
The development of a nomogram to determine the risk for inappropriate opioid use in cancer patients.
Authors: Sriram J. Yennu, Rony Dev, Tonya Edwards, Joseph Anthony Arthur, Zhanni Lu, Elif Erdogan, Jimi S. Malik, Syed M. Naqvi, Jimin Wu, Diane D. Liu, Janet L. Williams, David Hui, Suresh Reddy, Eduardo Bruera
Journal: Journal of Clinical Oncology (2019)

11602 Background: Non-Medical opioid use is a growing crisis. Cancer patients at risk of harmful use of prescribed opioids are frequently underdiagnosed. The aim was to develop a nomogram to predict the probability of occurrence of Inappropriate opioid use that is, presence of SOAPP ≥ 7) among patients receiving outpatient supportive care consultation at a comprehensive cancer center. Methods: 3588 consecutive cancer patients referred to a supportive care clinic from March 1, 2016 to July 15, 2018 were reviewed. Patients were eligible if they had diagnosis of cancer, and were on opioids for pain for at least a week. All patients were assessed using Edmonton Symptom Assessment Scale with spiritual pain and financial distress (ESAS-FS), MEDD (morphine equivalent daily dose), SOAPP-14 (validated questionnaire for assessment of risk of inappropriate opioid use, and CAGE-AID (screening questionnaire for alcoholism/substance use disorder). Patients at with SOAPP+ were defined by SOAPP score ≥7. A nomogram was devised based on the risk factors determined in the multivariate logistic regression model and it can be used to estimate the probability of inappropriate opioid use. Results: Median age was 62yrs. Median ESAS pain item score on consultation was 5, Median ECOG was 2.20.4% were SOAPP+ and 10.1% were CAGE-AID+. SOAPP+ was significantly associated with gender, race, marital status, smoking status, depression, anxiety, financial distress, MEDD and CAGE score. The C-index is 0.8(CI 0.78, 0.82). A nomogram was developed. For example, for a male Hispanic patient, who is married, never smoked, with the following ESAS scores: (depression = 3, anxiety = 3, financial distress = 8), CAGE score of 0, and MEDD of 20, the total score is 9+9+0+0+6+10+26+0+1 = 61. In the nomogram a score of 58 indicates the probability of inappropriate opioid use being 0.1 and a score of 88 indicates the probability of 0.2. Based on the patient’s total score of 61, the probability of his aberrant behavior is between 10% to 20% (close to 10%). Conclusions: A nomogram can predict the risk of inappropriate opioid use in cancer patients.
Different clinical outcome of metastatic colorectal cancer (MCRC) patients treated with intensive triplet chemotherapy plus bevacizumab (FIr-B/FOx) according to <i>KRAS </i>genotype and disease extension.
Authors: Gemma Bruera, Katia Cannita, Daniela Di Giacomo, Aude Lamy, Giancarlo Troncone, Antonella Dal Mas, Gino Coletti, Thierry Frébourg, Jean-Christophe Sabourin, Mario Tosi, Corrado Ficorella, Enrico Ricevuto
Journal: Journal of Clinical Oncology (2012)

e14010 Background: Bevacizumab (BEV) plus triplet chemotherapy can increase efficacy of first-line treatment of MCRC, particularly if integrated with secondary liver surgery in liver-limited (L-L) patients (pts). Clinical outcome of FIr-B/FOx regimen was evaluated according to KRAS genotype in L-L and other MCRC pts. Methods: Tumoral and metastatic samples were screened for KRAS codon 12 and 13, and BRAF mutations by SNaPshot and/or direct sequencing. MCRC pts were classified as L-L and other or multiple metastatic (O/MM). Activity and efficacy were evaluated and compared using log-rank test. Results: Fifty-nine pts were evaluated: 31 KRAS wild-type, 53%; 28 KRAS mutant, 47%. At 21.5 months median follow-up, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were, respectively: KRAS wild-type 90%, 14 months, 38 months; KRAS mutant 67%, 11 months, 20 months. PFS and OS were, respectively: overall in 25 L-L compared to 32 O/MM evaluable pts, 17 and 12 months, 47 and 21 months, significantly different; in KRAS wild-type, 12 L-L compared to 18 O/MM, 21 and 12 months, 47 and 28 months, significantly different; in KRAS mutant, 13 L-L compared to 14 O/MMS, 11 months equivalently, 39 and 19 months, not significantly different. Conclusions: First line FIr-B/FOx regimen can increase activity and efficacy of KRAS wild-type and mutant MCRC pts; integration with secondary liver surgery significantly discriminates increased clinical outcome in KRAS wild-type L-L compared to O/MM pts while not in KRAS mutant pts.
ERCC1 mRNA expression and XRCC1 polymorphism as predictive factors for overall survival in gastric cancer patients receiving platinum based chemotherapy
Authors: J. Wei, B. Liu, Z. Zou, X. Qian, W. Zhang, L. Yu
Journal: Journal of Clinical Oncology (2007)

2512 Background: DNA repair was considered to play the key role in the platinum chemotherapy. ERCC1, XPD and XRCC1, three major components of the DNA repair pathway, are critical to outcome for patients treated with platinum based chemotherapy. Methods: Overall survival times in 48 stage III (47.9%) and IV (52.1%) gastric cancer patients were investigated. mRNA was isolated from formalin- fixed paraffin-embeded pretreatment primary tumor specimens and the relative expression of ERCC1 to the internal reference geneβ-actin was measured using real-time quantitative reverse transcriptase polymerase chain reaction. Two single nucleotide polymorphisms (SNPs) (XPD Lys751Gln and XRCC1 Arg399Gln) were also investigated using 5’ nuclease allelic discrimination assay (TaqMan). Results: Median age was 55 years (range: 23 to 75 years); 35 males and 13 females; median survival time was 397 days. The median ERCC1 gene expression level from all 48 gastric tumors was 1.16, and the cutoff values for chemotherapy was 0.30. The median survival time for patients with lower ERCC1 expression (31 of 48 patients) was 496 days, compared with 218 days for patients with higher ERCC1 expression (P &lt; 0.0001). SNP of XRCC1 Arg399Gln was measured in 47 gastric cancer patients (97.92%). Median overall survival time was longer in patients with favorite allele G in codon 399 of XRCC1 (40 of 47 patients) than in others (respectively 420 days vs 218 days, P = 0.017). No significant relationship was found between SNP of XPD Lys751Gln and outcome of gastric cancer patients. Conclusions: These findings suggested that intratumoral ERCC1 mRNA expression and polymorphism of XRCC1 might be prominent predictive factors for overall survival of gastric cancer patients treated with platinum based chemotherapy. Multi-center clinical trial has been suggested. No significant financial relationships to disclose.
Screening of <i>CHEK2</i> and <i>TP53 p.R337H</i> germ-line mutations in high-risk patients for hereditary breast and ovarian cancer from northeast of Brazil.
Authors: Ivana Lucia Oliveira Nascimento, Gabriela Espirito Santo Felix, Taisa Manuela Bonfim Machado-Lopes, Thais Bomfim, Maura Romeo, Betania Toralles, Bernardo Garicochea, Roberto Meyer, Kiyoko Abe-Sandes
Journal: Journal of Clinical Oncology (2013)

1539 Background: CHEK2 is a molecular messenger that interacts with a checkpoint network of other susceptibility genes like ATM, BRCA1, TP53, MDM2, Cdc25A and Cdc25C. The mission of these checkpoints is to preserve the genome integrity during the cell division by regulating the cellular response to DNA damages. The TP53 p.R337H germline mutation was studied in patients with Li-Fraumeni Syndrome, breast cancer and Choroid plexus carcinomas in Southern of Brazil, but never in the Northeast. In the hereditary breast cancer the mutation frequencies of susceptibility genes of low penetrance like CHEK2 is 1-10%, while for genes of high penetrance as TP53 is &lt;1%. Thus, the aim of this study was to screening for CHEK2 and TP53 most common germline mutations in high-risk patients for hereditary breast and ovarian cancer (HBOC) from Northeast of Brazil. Methods: It was analyzed 100 high-risk patients for HBOC from Bahia, Brazil. The genomic DNA was extract from peripheral blood. The CHEK2 mutations, c.1100delC, c.444+1G&gt;A and p.I157T, and TP53 p.R337H mutation were genotyped by Allelic Specific-PCR or PCR-RFLP. Results: Most of the subjects had only breast cancer (86.0%), followed by ovarian (7.0%) and both breast and ovarian cancer (7.0%). Among the breast cancer cases the most common histological type was the ductal (71.0%), while among the ovarian cancer cases were the serous (57.14%). The mean age at diagnostic was 42 yrs (± 9.99). Any of the patient presented c.1100delC, c.444+1G&gt;A and p.I157T mutations. But, two have the p.R337H mutation. Conclusions: Though there is the hypothesis that mutations of low penetrance genes, such as CHEK2, are more likely to be found than high penetrance genes, such as TP53, here it was demonstrate that three of most predisposing variants of CHEK2, c.1100delC, c.444+1G&gt;A and p.I157T, do not have major contribution in HBOC in the population studied. While, the p.R337H, though presented in low frequency compared with the Southern of Brazil (Ashton-Prolla et al., 2012), seems to have a significant contribution in HBOC.
Antibody barriers to going viral
Authors: Dennis R. Burton
Journal: The Journal of Experimental Medicine (2019)

Antibody neutralization of a virus in vitro is often associated with protection against viral exposure in vivo, but the mechanisms operational in vivo are often unclear. By investigating a large number of antibodies, Earnest et al. (https://doi.org/10.1084/jem.20190736) show the importance of antibody effector function in neutralizing antibody protection against an emerging alphavirus in a mouse model.
NCI 8609: Interim fluoro-3’-deoxythymidine (FLT) PET imaging findings from the phase I trial of PARP inhibitor veliparib (V) and carboplatin (C) in advanced breast cancer.
Authors: Bhuvaneswari Ramaswamy, Jun Zhang, Nathan Hall, Katharina Schregel, Maryam B. Lustberg, Robert Wesolowski, Ewa Mrozek, Rachel M. Layman, Erin Macrae Olson, Susan Ottman, Andrea Camp, Jeffrey J. Chalmers, Susan Michelle Geyer, Miguel Angel Villalona-Calero, Charles L. Shapiro, Michael R. Grever, Michael V. Knopp
Journal: Journal of Clinical Oncology (2013)

1023 Background: We are currently conducting a phase I trial of PARP inhibitor, V on an intermittent (7 or 14 day) or continuous (21 day) schedule in combination with C in patients (pts) with advanced breast cancer. We are using FLT PET/CT sequentially to assess DNA damage induced by varying dose schedules of PARP inhibitor, where uptake of FLT depends on the proliferation rate of the tumor. Methods: Eligible pts received C-AUC 5 Q 3weeks (except dose level 1-AUC 6) plus escalating doses of V, BID on 7, 14, or 21-day schedules based on a standard 3+3 dose escalation design. We performed FLT PET/CT at baseline, cycle 1 day 7 and 14 and after cycle 3. Lesions were track-matched with the FDG PET/CT and semi-quantitatively assessed using 2D ROI placement in a matched, blinded fashion. Results: 38 pts have been accrued to 7 dose levels and FLT-PET imaging was successfully obtained in all pts with the proliferative whole body mapping revealing expected bone-marrow, liver and RESuptake. FLT-PET uptake showed a significant (p &lt; 0.001) decrease between baseline and day 7 (N = 25) with an overall trend to rebound nearly to baseline at day 14 for pts that did not show a significant decrease in FLT uptake reduction after cycle 3. The 14-day (n = 15) dosing schedule resulted in more pronounced day 14 reduction in FLT uptake when compared to those on the 7-day (n = 7) schedule. A FLT rebound to baseline level appeared to be associated with limited therapy response. There were no reported toxicities from FLT imaging. Conclusions: FLT-PET was consistently obtained with excellent whole body quality. All lesions revealed a FLT (proliferation) uptake that was different from the FDG (metabolism) uptake. FLT uptake indicated an initial reduction of proliferation at day 7, followed by a rebound at day 21 in all patients on the 7 or 14 day schema. The trial protocol was therefore amended to include a 21 day schema which is currently still ongoing. FLT appears to be a promising in-vivo imaging marker that may serve as a guiding tool to optimize dosing schema in addition to assessing/ predicting overall response. Study support- U01 CA076576 /Wright Center of Innovation ODSA TECH09-028. Clinical trial information: NCT01251874.
MELK mediates the stability of EZH2 through site-specific phosphorylation in extranodal natural killer/T-cell lymphoma
Authors: Boheng Li, Junli Yan, The Phyu, Shuangyi Fan, Tae-Hoon Chung, Nurulhuda Mustafa, Baohong Lin, Lingzhi Wang, Pieter Johan Adam Eichhorn, Boon-Cher Goh, Siok-Bian Ng, Dennis Kappei, Wee-Joo Chng
Journal: Blood (2019)
Helen Salisbury: Balancing patient safety and autonomy
Authors: Helen Salisbury
Journal: BMJ (2019)

If a 90 year old is climbing ladders, should your first instinct be to congratulate her or to warn her of the dangers? I discussed this recently with a friend, whose elderly patient kept chickens that had taken to roosting in the trees. On balance, we agreed that the benefit of tending her allotment and chickens probably outweighed the risks of ladder climbing, even though her balance wasn’t what it used to be.

Nearly five years after the publication of Atul Gawande’s Being Mortal , with its urgent call to reconsider how our society …
How sport and exercise medicine research can protect athlete health and promote athlete performance
Authors: Margo Mountjoy, Lars Engebretsen
Journal: British Journal of Sports Medicine (2019)

American swimming legend, Fran Crippen died on the 23 October 2010 during an open water FINA World Cup event in the heat of Dubai. His untimely death—likely as a result of hyperthermia but never confirmed1—directly led to FINA implementing a limit to how hot water could be for swimming competitions. FINA refers to this as the ‘upper limit safe water temperature rule’.2 This rule followed extensive collaborative research with the IOC and the International Triathlon Union (ITU) to investigate how swimmers respond to varying degrees of warm water temperature. Utilising sport medicine and science research to determine rule changes should be ‘the gold standard’ practice to protect athlete health.

Some of the larger International Sporting Federations, such as football (FIFA), aquatics (FINA), athletics (International Association of Athletics Federation (IAAF)) and skiing (Ski Federation (FIS)) self-fund scientific research on athlete safety; other International Federations accomplish a similar outcome through collaboration with academic institutions that garner research grants from various sources. The IOC funds targeted research through Olympic Solidarity and the IOC Medical and Scientific Commission. In addition, the IOC now has 11 research centres worldwide that carry out sport science research that protects athlete health. This editorial highlights four categories of initiatives by International Federations for athlete protection. All have been …
C3a primes B cell responses to SDF-1/CXCL12 by increasing its binding affinity to the CXCR4 chemokine receptor
Authors: M. Honczarenko, M. Swierkowski, Y. Le, A. M. Glodek, M. Z. Ratajczak, A. Nicholson Weller, L. E. Silberstein
Journal: Blood (2003)
How to start an antimicrobial stewardship programme in a hospital
Authors: M. Mendelson, A.M. Morris, K. Thursky, C. Pulcini
Journal: Clinical Microbiology and Infection (2019)

BackgroundAntimicrobial stewardship (AMS) describes a coherent set of actions that ensure optimal use of antimicrobials to improve patient outcomes, while limiting the risk of adverse events (including antimicrobial resistance (AMR)). Introduction of AMS programmes in hospitals is part of most national action plans to mitigate AMR, yet the optimal components and actions of such a programme remain undetermined.ObjectivesTo describe how health-care professionals can start an AMS programme in their hospital, the components of such a programme and the evidence base for its implementation.SourcesNational and society-led guidelines on AMS, peer-reviewed publications and experience of AMS experts conducting AMS programmes.ContentWe provide a step-by-step pragmatic guide to setting up and implementing a hospital AMS programme in high-income or low-and-middle-income countries.ImplicationsAntimicrobial stewardship programmes in hospitals are a vital component of national action plans for AMR, and have been shown to significantly reduce AMR, particularly when coupled with infection prevention and control interventions. This step-by-step guide of 'how to' set up an AMS programme will help health-care professionals involved in AMS to optimally design and implement their actions.
Doctor, how long?
Authors: A. B. Fêde, V. da Costa Miranda, F. D. Martins, N. P. Magalhães, H. L. Schaffhausser, R. P. Riechelmann, A. Del Giglio
Journal: Journal of Clinical Oncology (2009)

e20653 Background: In practice it is common to start terminal sedation for patients with advanced cancer who develop physical discomfort not amenable to be treated by other means. We aimed at quantifying the average survival time of terminal cancer patients once sedation was started until death and identify potential variables that may influence their survival time on sedation. Methods: This is a retrospective cohort analysis of all consecutive terminal cancer patients who died after starting terminal sedation at public tertiary brazilian Hospital during 2 years (January 2005 to January 2007). Results: 532 cancer patients died in Hospital Estadual Mário Covas during this period and 181 out of them who received terminal sedation were included in this analysis. The median survival was 27 hours. By multivariate analysis, increase in the dose of sedative drug during sedation (Odds Ratio 1.576, 95% CI 1.113–2.232); use of opioids alone for sedation (Odds Ratio 1.438, 95% CI 1.046–1.977); and dyspnea as cause of sedation (Odds Ratio 1.564 95% CI 1.045–2.341) were independent risk factors for a shorter survival time after starting terminal sedation. Conclusions: Sedated, terminal cancer patients usually live about one day. We identified risk factors for a shorter sedation period. This study is limited by its retrospective design and by the frequent use of opioids as the main sedative medications. Prospective studies must be carried out in order to validate these data in settings in which non-opiods are the main sedative medications. No significant financial relationships to disclose.
Personalized Prognostic Predictions for Patients with Myeloproliferative Neoplasms through Integration of Comprehensive Genomic and Clinical Information
Authors: Jacob Grinfeld, Jyoti Nangalia, E. Joanna Baxter, Anna L. Godfrey, Paola Guglielmelli, Rob Cantrill, David Wedge, Nicos Angelopoulos, Gunes Gundem, Charlie Massie, Elli Papaemmanuil, Cathy MacLean, Julia Cook, Francesca Lauren Nice, Christen Lykkegaard Andersen, Hans Carl Hasselbalch, Mary Frances McMullin, Alessandro M. Vannucchi, Claire N. Harrison, Moritz Gerstung, Peter J. Campbell, Anthony R. Green
Journal: Blood (2017)