tbuckley/cabot-search huggingface dataset:
Early-onset colorectal cancer in younger patients: A population-based study.
Authors: Hu Huang, Suwei Wang, Elisabeth Scheufele, Irene Dankwa-Mullan, Gretchen Purcell Jackson, Yull Edwin Arriaga
Journal: Journal of Clinical Oncology (2020)

124 Background: In the US, the incidence of colorectal cancer (CRC) is increasing in patients younger than 50 years who may present with advanced stage, high grade, left-sided colon or rectal cancers with signet ring cell histopathology, aggressive clinical course, and reduced overall survival. Understanding the characteristics of this population could inform screening, early detection, and optimal treatment. In this study, we describe the attributes of adults who are 50 years and younger with a first diagnosis of CRC and ascertain molecular testing rates and time to surgery by using data from a commercially insured cohort in the U.S. Methods: This retrospective study of patients ages 50 and younger with a first diagnosis of CRC utilizes the IBM MarketScan database, and focuses on claims from January 2013 to December 2018. Included patients had continuous insurance enrollment of 12 months before and 6 months after diagnosis. We determined rates of tumor testing for microsatellite instability (MSI) or immunohistochemistry (IHC) for mismatch repair (MMR) proteins and referral to genetic services in all patients, as well as mutational analysis of KRAS, NRAS, and BRAF in metastatic CRC patients. Time to surgical resection of primary tumor (TTS) in non-metastatic colon cancer patients was measured. Results: During the 5-year period, 10,577 patients ages 18 to 50 years had a first diagnosis of CRC, which was 15.6% of the 67,921 adults of all ages with CRC. Claims for MSI or IHC for MMR proteins within 120 days of initial diagnosis were done in 4,429 (41.9%) patients and referral to genetics services/counseling within 1 year of initial diagnosis were done in 443 (4.1%) patients. Among metastatic CRC patients, KRAS, NRAS, or BRAF tumor mutational analyses within 120 days of initial diagnosis were documented in 323 (31.5%). The median TTS ranged from 7 to 15 days with no statistically significant differences based on geographic region or health insurance plan type. Conclusions: Younger patients with early onset CRC had low rates of referral to genetics services, tumor MSI or IHC for MMR proteins testing, and KRAS, NRAS, and BRAF mutational analysis. There were no geographic or insurance type trends in TTS in non-metastatic colon cancer patients. Although underreporting is possible in our study, the findings of low utilization of genetic services and tumor genomic testing in these younger patients with early onset CRC should alert the oncology community to critical management gaps in the care of this population.
Identifying Important Clinical Symptoms in Children With Severe Neurological Impairment Using Parent-Reported Outcomes of Symptoms
Authors: James A. Feinstein, Chris Feudtner, Robert J. Valuck, Diane L. Fairclough, Jacqueline A. Holstein, Sadaf Samay, Allison Kempe
Journal: JAMA Pediatrics (2020)

This cross-sectional study evaluates whether the Parent-Reported Outcomes of Symptoms system identifies more symptoms than clinicians do among children with severe neurological impairment.
Age-sex specific pulmonary embolism-related mortality in the USA and Canada, 2000–18: an analysis of the WHO Mortality Database and of the CDC Multiple Cause of Death database
Authors: Stefano Barco, Luca Valerio, Walter Ageno, Alexander T Cohen, Samuel Z Goldhaber, Beverley J Hunt, Alfonso Iorio, David Jimenez, Frederikus A Klok, Nils Kucher, Seyed Hamidreza Mahmoudpour, Saskia Middeldorp, Thomas Münzel, Vicky Tagalakis, Aaron M Wendelboe, Stavros V Konstantinides
Journal: The Lancet Respiratory Medicine (2020)
iMOKA: k-mer based software to analyze large collections of sequencing data
Authors: Claudio Lorenzi, Sylvain Barriere, Jean-Philippe Villemin, Laureline Dejardin Bretones, Alban Mancheron, William Ritchie
Journal: Genome biology (2020)

Abstract iMOKA (interactive multi-objective k -mer analysis) is a software that enables comprehensive analysis of sequencing data from large cohorts to generate robust classification models or explore specific genetic elements associated with disease etiology. iMOKA uses a fast and accurate feature reduction step that combines a Naïve Bayes classifier augmented by an adaptive entropy filter and a graph-based filter to rapidly reduce the search space. By using a flexible file format and distributed indexing, iMOKA can easily integrate data from multiple experiments and also reduces disk space requirements and identifies changes in transcript levels and single nucleotide variants. iMOKA is available at https://github.com/RitchieLabIGH/iMOKA and Zenodo 10.5281/zenodo.4008947 .
Outcomes with sequential FLT3-inhibitor-based therapies in patients with AML
Authors: Musa Yilmaz, Mansour Alfayez, Courtney D. DiNardo, Gautam Borthakur, Tapan M. Kadia, Marina Y. Konopleva, Sanam Loghavi, Rashmi Kanagal-Shamanna, Keyur P. Patel, Elias J. Jabbour, Guillermo Garcia-Manero, Naveen Pemmaraju, Sherry A. Pierce, Issa Ghayas, Nicholas J. Short, Guillermo Montalban-Bravo, Koichi Takahashi, Rita Assi, Ahmad S. Alotaibi, Maro Ohanian, Michael Andreeff, Jorge E. Cortes, Hagop M. Kantarjian, Farhad Ravandi, Naval G. Daver
Journal: Journal of Hematology & Oncology (2020)

Second-generation FLT3-inhibitors (FLT3i) demonstrated single-agent composite CR rates (CRc) of 45-55% in patients with relapsed/refractory (R/R) FLT3-mutated AML in phase II/III trials. However, > 85% of patients treated were prior FLT3i naïve. The response rates to sequential FLT3i exposure remain poorly defined. We retrospectively reviewed patients with FLT3-mutated AML between November 2006 and December 2019. In frontline patients treated with a FLT3i (cohort 1), the CRc rates and median overall survival (OS) with the first (n = 56), second (n = 32), and third FLT3i-based (n = 8) therapy were 77%, 31%, and 25%, and 16.7 months, 6.0 months, and 1.4 months, respectively. In patients receiving a FLT3i-based therapy for the first time in a R/R AML setting (cohort 2), the CRc rates and median OS were 45%, 21%, and 10%, and 7.9 months, 4.0 months, and 4.1 months with the first (n = 183), second (n = 89), and third/fourth (n = 29) FLT3i-based therapy, respectively. In cohort 1, CRc rates with single-agent FLT3i (n = 21) versus FLT3i-based combinations (n = 19) in second/third sequential FLT3i exposures were 19% versus 42%, respectively. In cohort 2, the CRc rates with single-agent FLT3i (n = 82) versus FLT3i-based combinations (n = 101) in first FLT3i exposure were 34% versus 53%, respectively, and those with single-agent FLT3i (n = 63) versus FLT3i-based combinations (n = 55) in second/third/fourth sequential FLT3i exposures were 13% versus 25%, respectively. CRc rates drop progressively with sequential exposure to FLT3i's in FLT3-mutated AML. In all settings, CRc rates were higher with FLT3i-based combinations compared with single-agent FLT3i therapy in similar FLT3i exposure settings.
Dye‐Loaded Nanoemulsions: Biomimetic Fluorescent Nanocarriers for Bioimaging and Nanomedicine
Authors: Andrey S. Klymchenko, Fei Liu, Mayeul Collot, Nicolas Anton
Journal: Advanced Healthcare Materials (2020)

Abstract Lipid nanoemulsions (NEs), owing to their controllable size (20 to 500 nm), stability and biocompatibility, are now frequently used in various fields, such as food, cosmetics, pharmaceuticals, drug delivery, and even as nanoreactors for chemical synthesis. Moreover, being composed of components generally recognized as safe (GRAS), they can be considered as “green” nanoparticles that mimic closely lipoproteins and intracellular lipid droplets. Therefore, they attracted attention as carriers of drugs and fluorescent dyes for both bioimaging and studying the fate of nanoemulsions in cells and small animals. In this review, the composition of dye‐loaded NEs, methods for their preparation, and emerging biological applications are described. The design of bright fluorescent NEs with high dye loading and minimal aggregation‐caused quenching (ACQ) is focused on. Common issues including dye leakage and NEs stability are discussed, highlighting advanced techniques for their characterization, such as Förster resonance energy transfer (FRET) and fluorescence correlation spectroscopy (FCS). Attempts to functionalize NEs surface are also discussed. Thereafter, biological applications for bioimaging and single‐particle tracking in cells and small animals as well as biomedical applications for photodynamic therapy are described. Finally, challenges and future perspectives of fluorescent NEs are discussed.
Patient characteristics associated with time-to-consult for inpatient palliative radiotherapy.
Authors: Jon X Wang, Lauren Boreta, Emily Yee, Steve E. Braunstein, Julian C. Hong
Journal: Journal of Clinical Oncology (2020)

27 Background: Delayed inpatient radiotherapy (RT) consultation can result in delayed treatment, extended hospitalization, and increased costs. There are limited data characterizing populations that may have longer time-to-consult (TTC). Methods: A single institutional electronic health record deidentified corporate data warehouse was used to identify adult inpatients with a consultation to radiation oncology between 2014-2019. TTC was defined as time from admission to placement of consultation. Multivariate linear regression was used to examine adjusted associations for factors including age, diagnosis, admission date, admitting service, and patient-reported sex, race and ethnicity to TTC. Continuous variables were normalized to generate standardized beta coefficients (B). Results: A total of 856 admissions with radiation oncology consult were identified. Median TTC was 21 hours (interquartile range [IQR] 5-69). Median age was 61 (IQR 49-68) and 51% of patients were male. Most patients were white (58%) and non-Hispanic or Latino (80%). The most common admission primary diagnoses were brain metastasis (14%), bone metastasis (10%), and primary brain neoplasm (9%), Most common admitting services were Neurosurgery (49%), Hospital Medicine (22%), Malignant Hematology (8%), and Gynecologic Oncology (8%). Primary brain neoplasms (vs brain metastases B = 64; P &lt; .001), other non-metastatic diagnoses (vs brain metastases B = 45; P &lt; .001) and admission on the malignant hematology service (vs neurosurgery; B = 37; P = .03) were associated with longer TTC. Patient demographic characteristics (age sex, race, ethnicity), and admission date did not have significant associations with TTC. Longer TTC was correlated with longer hospitalization (Pearson’s corr = 0.48). Conclusions: No clear demographic disparities in inpatient RT consultation were identified. Certain diagnoses and services were associated with longer TTC, potentially related to clinical practice. Increased TTC was associated with longer hospital length of stay.
CD19-specific CAR T Cells that Express a PD-1/CD28 Chimeric Switch-Receptor are Effective in Patients with PD-L1–positive B-Cell Lymphoma
Authors: Hui Liu, Wen Lei, Chaoting Zhang, Chunmei Yang, Juying Wei, Qunyi Guo, Xiaojun Guo, Zhilu Chen, Ying Lu, Ken H. Young, Zheming Lu, Wenbin Qian
Journal: Clinical Cancer Research (2020)

CD19-specific chimeric antigen receptor (CAR) T-cell therapy is effective against refractory or relapsed (R/R) B-cell lymphoma, but the efficacy is hindered by the existence of PD-1/PD-L1 pathway.
Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors
Authors: Albiruni RA Razak, James M Cleary, Victor Moreno, Michael Boyer, Emiliano Calvo Aller, William Edenfield, Jeanne Tie, R Donald Harvey, Annemie Rutten, Manish A Shah, Anthony J Olszanski, Dirk Jäger, Nehal Lakhani, David P Ryan, Erik Rasmussen, Gloria Juan, Hansen Wong, Neelesh Soman, Marie-Anne Damiette Smit, Dirk Nagorsen, Kyriakos P Papadopoulos
Journal: Journal for ImmunoTherapy of Cancer (2020)

To determine the safety and efficacy of the anti-colony-stimulating factor 1 receptor (anti-CSF1R) monoclonal antibody AMG 820 in combination with pembrolizumab in patients with select solid tumors.Patients had advanced, refractory mismatch repair-proficient colorectal cancer, pancreatic cancer, or non-small cell lung cancer (NSCLC) with low (<50%) programmed cell death-ligand 1 (PD-L1) expression and were naïve to anti-programmed cell death-1 (PD-1)/PD-L1 or had relapsed/refractory NSCLC after anti-PD-1/PD-L1 treatment with low or high (≥50%) PD-L1 expression; all were anti-CSF1/CSF1R naïve. Patients received 1100 mg or 1400 mg AMG 820 plus 200 mg pembrolizumab intravenously every 3 weeks. The primary endpoints were incidence of dose-limiting toxicities (DLTs) and adverse events (AEs) and objective response rate per immune-related Response Evaluation Criteria in Solid Tumours at the recommended combination dose.Overall, 116 patients received ≥1 dose of AMG 820 plus pembrolizumab (18 at 1400 mg AMG 820; 98 at 1100 mg AMG 820). Most patients (64%) were male; the median age was 64 (range 30-86) years. Seven patients had DLTs (1 at 1400 mg AMG 820; 6 at 1100 mg AMG 820). Almost all patients (99.1%) had AEs, 87.9% with grade ≥3 AEs. The most common AEs were increased aspartate aminotransferase (59.5%), fatigue (48.3%), periorbital/face edema (48.3%), and rash/maculopapular rash (37.1%). The best response was immune-related partial response in 3 patients (3%; duration of response 9.2, 10.0, 12.5 months) and immune-related stable disease in 39 patients (34%). None of the completed phase II cohorts met the predefined threshold for efficacy. Post-treatment there was accumulation of serum colony-stimulating factor 1 (CSF1) and interleukin-34, reduction in CSF1-dependent CD16-expressing monocytes, and increased PD-L1 expression and CD4 and CD8 cell numbers in tumor biopsies.The recommended combination dose of 1100 mg AMG 820 plus 200 mg pembrolizumab had an acceptable safety profile. Although pharmacodynamic effects were observed, antitumor activity was insufficient for further evaluation of this combination in selected patient populations.NCT02713529.
Advances and Challenges in Pediatric and Childhood Cancers
Authors: Cynthia Hawkins, Stefan Pfister, David T.W. Jones, Nirali N. Shah, Richard J. Gilbertson, E. Alejandro Sweet-Cordero, Michael A. Dyer, Yael P. Mossé, Michelle Haber, Steven G. DuBois
Journal: Cancer Cell (2020)
Longitudinal egg‐specific regulatory T‐ and B‐cell development: Insights from primary prevention clinical trials examining the timing of egg introduction
Authors: Catherine L. Lai, Dianne E. Campbell, Debra J. Palmer, Maria Makrides, Brigitte Santner‐Nanan, Michael Gold, John Wei‐Liang Tan, Carol Valerio, Ralph Nanan, Susan L. Prescott, Peter S. Hsu
Journal: Allergy (2020)

Egg allergy affects almost 1 in 10 Australian infants. Early egg introduction has been associated with a reduced risk in developing egg allergy; however, the immune mechanisms underlying this protection remain unclear.To examine the role of regulatory immune cells in tolerance induction during early egg introduction.Cryopreserved peripheral blood mononuclear cells (PBMC) were obtained from infants from 2 randomized controlled trials of early introduction of egg for the primary prevention of egg allergy; BEAT (at 12 months, n = 42) and STEP (at 5 months n = 82; 12 months n = 82) study cohorts. In vitro ovalbumin-stimulated PBMC were analyzed by flow cytometry for presence of ovalbumin-specific regulatory T cells, using activation markers, FoxP3, and IL-10 expression. Ovalbumin-specific regulatory B cells were identified by co-expression of fluorescence-conjugated ovalbumin and IL-10.Specific, age-dependent expansion of ovalbumin-specific regulatory T cells was only observed in infants who (a) had early egg introduction and (b) did not have egg allergy at 12 months. This expansion was blunted or impaired in children who did not undergo early egg introduction and in those with clinical egg allergy at 12 months. Infants with egg allergy at 12 months of age also had reduced frequency of ovalbumin-specific regulatory B cells compared to egg-tolerant infants.Early egg introduction and clinical tolerance to egg were associated with expansion of ovalbumin-specific T and B regulatory cells, which may be an important developmental process for tolerance acquisition to food allergens.
2,5-dimethylcelecoxib improves immune microenvironment of hepatocellular carcinoma by promoting ubiquitination of HBx-induced PD-L1
Authors: Zhanfei Chen, Yiyin Chen, Lirong Peng, Xiaoqian Wang, Nanhong Tang
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background 2,5-dimethylcelecoxib (DMC) is a targeted inhibitor of microsomal prostaglandin E synthase-1 (mPGES-1), a key enzyme in the PGE2 synthesis pathway of inflammatory mediators. Previous studies have confirmed that DMC can inhibit the growth of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, it is not known whether DMC is involved in the changes of tumor immune microenvironment. Methods In this study, we explored the effects of DMC on HBV-related HCC immune microenvironment, and deeply analyzed its unique effect and mechanism on programmed death receptor 1 (PD-1)/and its ligand 1 (PD-L1) pathway. Results Clinical hepatoma tissues detection showed that compared with non-virus-related HCC, the level of CD8 of HBV-related HCC was significantly lower, while the levels of PD-L1 and CD163 were higher. In vivo experiments indicated that DMC could increase the level of tumor infiltrating CD8 + T cells in hepatitis B virus X (HBx) (+) hepatoma cells implanted mouse models, and inhibit the expression of PD-L1 and CD163 in tumor tissues. DMC combined with atezolizumab had more significant antitumor effect and stronger blocking effect on PD-1/PD-L1 pathway. Mechanism studies have shown that DMC can promote ubiquitin degradation of HBx-induced PD-L1 protein in HCC cells by activating adenosine 5′-monophosphate-activated protein kinase pathway. Further experiments confirmed that this process was mainly mediated by E3 ligase RBX1. Conclusions Our results uncover a role for DMC in promoting HBV-related HCC immune microenvironment, which not only enrich the relationship between inflammatory factors (mPGES-1/PGE2 pathway) and immunosuppression (PD-L1), but also provide an important strategic reference for multitarget or combined immunotherapy of HBV-related HCC.
Prognostic value of the “surprise question” among UPMC Hillman Cancer Center patients with select stage IV cancer diagnoses.
Authors: Kristine Gade, Neal Spada, Ellen Ormond, Mamta Bhatnagar, Maria Guyette, Aaron Brown, Kevin Cullison, Roby Antony Thomas
Journal: Journal of Clinical Oncology (2020)

25 Background: The “Surprise Question” — Would I be surprised if this patient died in the next 12 months? — was developed to help clinicians predict when patients are nearing the end of life. Limited data has shown that the “Surprise Question” is modestly predictive of mortality (CMAJ 2017 Apr 3;189(13):E484-E493), though its performance seems to be superior among cancer patients (Palliat Med 2014 Jul;28(7):959-964). Via Oncology Pathways, a platform used by UPMC Hillman Cancer Center and other institutions nationwide to guide treatment decisions, asks physicians the “Surprise Question” when a new treatment plan is implemented for patients with metastatic cancer. We assessed the “Surprise Question’s” ability to predict survival among Hillman Cancer Center patients with select stage IV diagnoses. Methods: We queried the UPMC Hillman Cancer Center Registry Information and Reporting Services for cases of colorectal, non-small cell lung, prostate, pancreatic, and breast cancer with clinic visits between 1/1/2016 and 12/31/2017 and residence in Allegheny County, the primary referral base for the UPMC Hillman Cancer Center network’s flagship facility. Results: The “Surprise Question” was completed for 1,584 patients with metastatic disease of the 5,330 patients that were screened. “No” was the response for 891 patients (56.3%). Mortality at 12 months for patients for whom the answer to the “Surprise Question” was “no” was 63.1%, compared to 32.5% for patients for whom the answer was “yes” (P &lt; 0.0001). The sensitivity of the “Surprise Question” was 71.4% (95% CI 69.0 – 73.8%), and the specificity was 58.7% (95% CI 56.3 – 61.0%). The positive predictive value was 63.1% (95% CI 60.9 – 65.2%) and negative predictive value 67.5% (64.8% – 70.2%). Finally, the positive likelihood ratio was 1.73 (95% CI 1.58 – 1.89) and negative likelihood ratio 0.49 (0.43 – 0.55). Conclusions: While a “no” response to the “Surprise Question” for UPMC oncology patients with select stage IV diagnoses was more likely to predict 12-month mortality than a “yes” response, the “Surprise Question” was only modestly predictive of 12-month mortality. Future work will focus on determining if there are patient populations for whom the “Surprise Question” is more predictive and assessing the ability of the “Surprise Question” to predict other clinical outcomes, such as ED visits and hospitalizations.
Optimization of the triage nurse's time by decreasing time spent on non-nursing functions.
Authors: Jennifer Pugh, Dhaval Shah, Lee Ann Ladics, Elizabeth Wade
Journal: Journal of Clinical Oncology (2020)

293 Background: Triage nurses are an essential part of the multidisciplinary management of the oncology patient. Because of the nature of their role, they spend a significant amount of time performing non-nursing functions, resulting in a delay in patient care and decreased job satisfaction. This study will examine whether implementing a central phone triage system and commensurate process improvements in a large oncology practice will decrease the amount of time that the triage nurses spend on non-nursing functions. Methods: Nine triage nurses at our practice participated in a survey to obtain baseline data. The survey focused on data regarding the non-nursing issues that are encountered during the work day. We then developed a survey for the nurses to determine how much time per 8-hour work day, was spent on the identified non-nursing functions. A new telephone operator system was evaluated for suitability and then implemented. With the new system, the central operator answers all phone calls coming into the practice, and directs them to appropriate department via a messaging system, thus eliminating phone calls to the triage nurses’ direct extensions. Two months after the implementation of this new system, we recollected data to measure the time spent on the previously identified non-nursing functions. A job satisfaction survey was collected pre- and post-study. Results: The initial data collected showed that triage nurses spent approximately 60 minutes per day on non-nursing functions. These functions included the following: the amount of time listening to and taking off patient messages, pre-cert issues, order clarifications and social work issues. The data collected after implementing a new telephone system showed that this time dropped to approximately 12 minutes per day, a 78% reduction in non-nursing calls received by nurses. Additionally, there was a 7% increase in the triage nurse job satisfaction. Conclusions: After implementing a new telephone operator system, the nurses at this large oncology practice were able to better optimize their time taking care of patient related nursing functions. This improved their work flow, increased their time performing direct patient care related functions, and increased their overall job satisfaction. During this process, we also learned the importance of taking triage nurses input to improve their job function. Further research is recommended to better define the role of the phone triage nurse with the multidisciplinary care team of complex hematology/oncology patients.