bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complicating breast cancer treatment: Reasons patients present to the ED.
Authors: Hsiung Jayla , Taneja Kamil , Patel Karan , Benedict William , Sprankle Kenyon , Diaz Michael J. , Cohen Jules A. 
Published: June 2023

e13668 Background: Breast cancer is a very common cancer that provides a significant amount of stress on patients’ lives. These patients can have many cancer-related complications, which lead them to present to the ED. However, few studies have identified common reasons for these patients to present to the ED and factors associated with high risk of admission. Methods: We utilized the 2006-2012 Nationwide Emergency Department Sample to identify the common primary diagnoses of breast cancer patients in the ED. A multivariate logistic regression was used to identify characteristics that were significantly associated with a higher chance of inpatient admission. A p-value less than 0.05 was considered significant. Results: Between 2006 and 2012, 2,160,701 breast cancer patients presented to the ED. Most patients were at least 80 years old (53.0%), female (99.1%), Medicare beneficiaries (64.4%), of the highest income quartile (26.2%), living in the South (36.8%), presented to non-trauma hospitals (52.7%), and presented to metropolitan non-teaching hospitals (44.8%). Most patients were admitted (53.1%). The most common primary diagnoses of breast cancer patients were chest pain (5.4%), urinary tract infection (3.3%), pneumonia (3.1%), secondary malignancy (3.0%), and cardiac arrhythmia (3.0%). The primary diagnoses associated with the highest risk of inpatient admission are the following: septicemia (odds ratio: 39.4, 95% confidence interval (CI): 33.8-45.9,p < 0.001), femur fracture (OR:19.1, 95% CI: 16.6-22.0,p < 0.001), secondary malignancy (OR:17.7, 95% CI: 16.2-19.4,p < 0.001), acute cerebrovascular disease (OR:5.8, 95% CI:5.3-6.3,p < 0.001), pneumonia (OR:4.9, 95% CI:4.7-5.2,p < 0.001), and complication of previous surgical or medical therapy (OR:2.2, 95% CI:2.0-2.3,p < 0.001). Primary diagnoses associated with a lower risk of admission are the following: contusion (OR:0.06, 95% CI:0.06-0.07,p < 0.001), abdominal pain (OR:0.14, 95% CI:0.13-0.15,p < 0.001), and connective tissue disorder (OR:0.17, 95% CI:0.16-0.19,p < 0.001). Interestingly, patients that paid with Medicaid (OR:0.84, 95% CI:0.79-0.89,p < 0.001) or private insurance (OR:0.89, 95% CI:0.86-0.93,p < 0.001) were less likely to be admitted. Furthermore, uninsured patients were also less likely to be admitted (OR:0.52, 95% CI:0.48-0.57, p < 0.001). Conclusions: Breast cancer patients frequently present to the ED for many reasons, with septicemia and femur being the most severe diagnoses. Physicians should keep these risk factors in mind to prevent these complications and reduce patient stress.
Association of patient age and insurance status with in-hospital mortality for patients with lung cancer.
Authors: Hsiung Jayla , Taneja Kamil , Patel Karan , Metz Kevin , Chen Steven , Benedict William , Wolfe Jared , Diaz Michael J. , Cohen Jules A. 
Published: June 2023

e13669 Background: In 2022, the National Cancer Institute estimated that more than 240,000 individuals will be diagnosed with lung cancer. Furthermore, over 130,000 patients will die. To help minimize this death rate, it is important to identify death risk factors. Methods: We utilized the 2006-2012 Nationwide Emergency Department Sample to identify risk risk factors for death in lung cancer patients. A multivariate logistic regression was used to identify patient and hospital characteristics that were significantly associated with a higher chance of in-hospital death. The top 20 primary diagnoses of these patients were included in the analysis to take into account the reason to visit the ED. A p-value less than 0.05 was considered significant. Results: During this time period, 1,344,817 lung cancer patients presented to the emergency departments (ED) across the US. The majority of patients at least 70 years old (50.8%), male (51.1%), Medicare beneficiaries (67.5%), of the lowest income quartile (28.1%), living in the South (40.3%), presented to non-trauma hospitals (54.3%), and presented to metropolitan non-teaching hospitals (43.3%). Out of the 1,344,817 lung cancer patients that presented to the ED, 6.1% died in the hospital. The primary diagnoses associated with increased mortality are the following: respiratory failure (odds ratio (OR): 9.05, 95% confidence interval (CI): 8.47-9.67, p < 0.001), septicemia (OR: 8.46, 95% CI: 7.98-8.97,p < 0.001), acute cerebrovascular disease (OR: 3.04, 95% CI: 2.71-3.35,p < 0.001), secondary malignancy (OR: 2.00, 95% CI: 1.88-2.13,p < 0.001), pulmonary heart disease (OR: 1.97, 95% CI: 1.75-2.20,p < 0.001), and pneumonia (OR: 1.90, 95% CI: 1.80-2.01, p < 0.001). Patients at least 70 years old (OR: 3.09, 95% CI: 1.72-5.53, p < 0.001), males (OR: 1.28, 95% CI: 1.24-1.32,p < 0.001), and uninsured patients (OR: 1.29, 95% CI: 1.15-1.46, p < 0.001) are patient groups at higher risk for in-hospital mortality. 5 primary diagnoses associated with decreased risk of death are the following: fluid/electrolyte disorder (OR: 0.81, 95% CI:0.70-0.93), p = 0.003), central nervous system disease (OR: 0.76, 95% CI: 0.640.91, p = 0.002), arrhythmia (OR: 0.74, 0.65-0.83, p < 0.001), anemia (OR:0.68, 95% CI: 0.55-0.83, < 0.001), complication related to previous surgery of medical therapy (OR:0.64, 95% CI:0.51-0.80, < 0.001), and chronic obstructive pulmonary disease (OR: 0.45, 95% CI: 0.39-0.62, p < 0.001). Conclusions: Older, uninsured, and male lung cancer patients are at high risk for in-hospital mortality. Patients presenting to the ED with respiratory failure and septicemia are at the highest risk for mortality.
Knowledge gaps and educational needs for common cancer therapy-related cardiovascular toxicities and related drug interactions.
Authors: Kaspari Sarah , Moore Heather , Beavers Craig , Hayes Sarah Maryon , Peterson Kristen , Yaseen Israa , Skersick Preston , Truitt Kelsey , Casselli Stephen , Rodgers Jo Ellen E. 
Published: June 2023

e13672 Background: Unprecedented growth in novel oncolytic agents has led to an increase in the complexity of cancer management, including cancer therapy-related cardiovascular toxicities (CTR-CVTs) and related pharmacodynamic (PD) and pharmacokinetic (PK) drug-drug interactions (DDIs). The intent of this survey is to assess the landscape of CTR-CVTs including health care provider (HCP) educational needs. Methods: A 20-question survey was distributed to HCPs primarily specializing in cardiology, oncology, hematology and cardio-oncology. The survey was distributed on email listservs of targeted organizations, including the International Cardio-Oncology Society. In addition to demographics, the survey assessed CTR-CVTs and related DDIs encountered. Perceived knowledge gaps were also assessed. Data was analyzed and summarized utilizing descriptive statistics. Results: Of 220 survey respondents, 46% were pharmacists and 54% were other HCPs ( > 80% physicians). Respondents predominately practiced in North America (59%) or Europe (20%), with the majority at academic medical centers (65% academic, 35% community) and primarily specializing in cardiology (71%, cardiology, 26% oncology, 14% hematology). Types of malignancies managed were primarily solid tumors (74%), however hematological malignancy management was also common ( > 60%). All HCPs reported encountering the following CTR-CVTs most commonly: cancer therapy-related cardiac dysfunction (CTRCD) (88%), hypertension (HTN) (79%) and thromboembolic disease (71%). Overall, pharmacists reported managing CTR-CVTs less frequently than other HCPs, especially regarding atrial fibrillation/flutter, coronary artery disease/vasospasm and bradycardia/AV block. The most common cardio-oncology-related PD DDIs encountered were CTRCD and QT prolongation/Torsades de Pointes (QTP/TdP). The most frequently managed cardio-oncology-related PK DDIs included antiarrhythmic agents, direct-acting oral anticoagulants and antiplatelet agents. All HCPs reported greatest comfort managing anthracycline/HER2 targeted therapy-associated CTRCD and least comfort managing arsenic-associated QTP. Immune checkpoint inhibitor-associated myocarditis (74%), immune modulator-associated thrombosis/thrombotic events (64%), Bruton tyrosine kinase inhibitor associated bleeding (58%) and atrial fibrillation (55%) were ranked of highest educational need. Overall, responses for PD/PK DDIs and educational recommendations were similar between pharmacists and other HCPs. Conclusions: This survey provides insight on the most commonly encountered CTR-CVTs and related DDIs as well as knowledge gaps of HCPs managing CTR-CVTs. These specific areas should be targeted for future educational initiatives to optimize the cardiovascular care of patients with cancer.
“You matter”: Patient reported outcomes on cancer disparities related to the COVID-19 pandemic.
Authors: Mohanna Mohamed , Sabbagh Saad , Dominguez Barbara , Itani Mira , Saba Ludovic , Iska Sindu , Liang Hong , Diaz Caroline , Nahleh Zeina A. 
Published: June 2023

e13674 Background: Disparities in cancer care have been exacerbated by the COVID-19 pandemic. Understanding the challenges encountered by patients can help alleviate the burden of cancer and improve access to care. Methods: We recruited consecutive patients with cancer at a comprehensive academic cancer center and analyzed patient reported socioeconomic and mental health challenges, and their perception of access to care since the start of the pandemic using a modified version of the You Matter: COVID-19 Mental Health Impact Survey. The survey instrument was self-administered once from November 11, 2022 to January 12, 2023 and consisted of 21 items with questions focused on demographics, social health, telehealth attitudes, and mental health. Established patients diagnosed at the cancer center prior to the start of the COVID-19 pandemic and who are continuing care were included in the study. Results: A total of 136 participants were included in this analysis. Participants characteristics were as follows: 70% had age>65, 75% white, 70% female, 43 % had bachelor's degree or higher, 62.5% with non-private insurance, 95% maintained same insurance throughout the pandemic, and 80% had household of > 1 person. Since April 2020, 49.3% reported increased level of stress and 60.6% reported increased anxiety, stress or experience of distress as a direct result of COVID-19. Among the patients that reported they had participated in telehealth, 84.4% described it as easy and effective, and 70.6% found it either comfortable or neutral. Black participants were more likely to have less contact with providers compared to white participants (OR=5.54, p=0.0180); participants age ≥65 were more likely to report worse overall health compared to younger participants (OR=2.67, p=0.0359); male participants were more likely to experience challenges because of COVID-19 (OR=2.12, p=0.0496), were less uncomfortable with telehealth (OR=0.034, p=0.0350), had increased anxiety and stress, and experienced less distress due to COVID19 (OR=0.47, p=0.0490) compared to female participants. Conclusions: Challenges reported during the COVID-19 pandemic varied across sociodemographic groups, with elderly, male and black reporting the worst impact related to the pandemic. The vast majority of the survey participants reported increased stress, anxiety, or distress affecting quality of life and hindering access to care. The results of the study, however, suggest the important role of telehealth in addressing challenges and narrowing disparities in access to cancer care across the majority of participants.
Barriers and facilitators to implementing the Veterans Health Administration National Teleoncology Service: A qualitative descriptive study.
Authors: King Heather , Kelley Michael J. , Blue Colleen , Miller Julie , Raska Whitney , McWhirter Gina , Pura John A. , Jeffreys Amy , Zullig Leah L. 
Published: June 2023

e13684 Background: Many Veterans lack local access to specialized cancer services. When timely VA care is not accessible, the VA covers the cost of care provided in a Veteran’s community. This benefit disrupts integrated care delivery within VA and may be less applicable for Veterans in areas where specialized cancer services may also not be available locally. The National TeleOncology (NTO) service was established to provide remotely delivered cancer services and increase access for Veterans to specialized cancer care. We sought to understand early implementation experiences as part of an ongoing evaluation of the VA National TeleOncology (NTO) service. Methods: Informed by the Consolidated Framework for Implementation Research (CFIR), we conducted a qualitative descriptive study using virtual individual interviews with Veterans (results not reported) and focus groups with clinicians. To identify and describe implementation barriers and facilitators, oncologists, nurse practitioners (NPs), and registered nurses (RNs) who provide care via teleoncology were asked about the need for NTO, its advantages/disadvantages compared to alternatives, and how to operationalize and measure NTO’s success. Additionally, Veterans who have participated in the teleoncology program were asked about their experiences; the analysis of this data is ongoing. We employed a team-based, rapid qualitative analysis using structured forms for notetaking. Theme matrix techniques facilitated data analysis and presentation. Findings were mapped to CFIR domains and constructs. Results: Guided by information power, we conducted 15 individual interviews with Veterans and three focus groups, separated by clinician type. The individual interviews lasted approximately 36 minutes, and focus groups lasted approximately 30 minutes. Most Veteran participants were male (87%), white (60%), and had prostate cancer (47%). Results from our analysis suggest that clinicians feel there are key challenges/barriers to engaging NTO: 1) can delay care; 2) perception that NTO may not be as personable as in-person care; 3) technology access/use can be difficult for some Veterans. They also reported key advantages/facilitators: 1) provides Veterans nationwide with accessibility to cancer specialists; 2) keeps patients in VA system to support better care coordination and team-based care that expedites needed follow-up services. Conclusions: Those involved in implementing NTO feel supported and that it works well overall, especially to provide better coordinated cancer care for Veterans. These data will support an ongoing NTO evaluation. Separate data collection efforts are underway to understand the quality of care delivered to inform the widespread scale-out and delivery of NTO.
Relationship between efficacy of phase I/II drug ispinesib in medulloblastoma, molecular subtypes, and p53-mutant status.
Authors: Teo Wan-Yee , Huang Shiying , Du Yuchen , Major Angela , Su Jack M. , Hui Kam Man , Elghetany M. Tarek , Li Xiao-Nan 
Published: June 2023

e14001 Background: KIF11, a mitotic kinesin, is responsible for assembly and maintenance of mitotic spindle during mitosis. Tumor cells can upregulate KIF11 to enhance tumor proliferation. Many cancers overexpress KIF11, including medulloblastoma (MB), the most common malignant brain tumor in children. MB is molecularly classified into 4 molecular subtypes: sonic-hedgehog (SHH)-activated MB, Wingless (WNT)-activated, and less characterized Group 3 and 4 subtypes. Group 3 and 4 MBs are the most aggressive subtypes and Group 3 MBs have the worst survival outcome. p53 mutation defines a high-risk group in MB patients. We evaluated the efficacy of a Phase I/II KIF11 inhibitor, ispinesib on MB. Methods: We employed in-vitro proliferation assays (CCK), flow cytometry (Annexin V, Propidium Iodide), western blot, Hoechst staining, and two patient-derived orthotopic xenograft (PDOX) mouse models for in-vivo drug testing. Results: Ispinesib effectively inhibited proliferation at nanomolar concentrations for all 5 MB cell lines. A comparison of IC50 (day 4) indicated that p53-mutational-status did not influence sensitivity to ispinesib. In all five cell lines, regardless of p53 mutational status, ispinesib led to G2/M arrest. However, different p53-mutational-status led to different modes of cell death. High levels of necrotic cell death were observed in p53-mutant, while apoptosis was the predominant mode of cell death in p53-wildtype, on flow cytometry. Apoptotic nuclei were more significantly observed in p53-wildtype (p = 0.002) while p53-mutant cell line demonstrated more micronuclei (p = 0.0302) and multi-nucleation (p= 0.0161), compared to respective DMSO-control cells on Hoechst staining. Ispinesib has demonstrated effective blood brain barrier penetration in brain xenografts. We compared 2 PDOX models of MB. Ispinesib significantly improved survival outcome of Group 3 MB (Control=6, Treated=7, Log-rank p=0.0003), but worsened the survival outcome of p53-mutant SHH MB (Control=14, Treated=11, Log-rank p=0.169). This differential efficacy of ispinesib was recapitulated in the matched 3D-neurosphere cultures of both PDOX models. Cancer-stem-cell (CSC)-enriched neurospheres derived from aggressive Group 3 subtype demonstrated susceptibility to 7-day in-vitro treatment with ispinesib (AUC=0.7743). Monolayer tumor cells demonstrated similar susceptibility (AUC=0.7757). Area under curve (AUC)>0.7 was the significant cut-off. In contrast, both CSC-enriched neurospheres (AUC=0.379) and monolayer tumor cells (AUC=0.491) derived from p53-mutant SHH MB did not demonstrate susceptibility to ispinesib, consistent with matching PDOX models. Conclusions: Preclinically, our results indicate feasibility of ispinesib treatment in MB, specifically aggressive Group 3 MB. Importantly, p53-mutant SHH MB represents a poor molecular-subtype candidate for ispinesib therapy.
Outcomes with bevacizumab for radiation induced-brain necrosis.
Authors: Muminovic Meri , Uribe Carlos Carracedo , Dalal Shivani , Castellon Ignacio , Falchook Aaron , Nano Olger , Raez Luis E. 
Published: June 2023

e14006 Background: Radiation necrosis (RN) is post-radiation complication that leads to increased permeability and disruption of the blood brain barrier (BBB). This in turn leads to a pro-inflammatory state and an increased production of vascular-endothelial growth factor (VEGF). Bevacizumab is a monoclonal antibody against VEGF and is a potential treatment for RN. The objective of the study is to assess effectiveness of bevacizumab (BEV) for the treatment of brain RN in adults. Methods: Retrospective chart review of 22 patients with various solid malignancies including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), metastatic melanoma and breast cancer with clinical or radiographic diagnosis of RN seen at Memorial Cancer Institute (MCI) in a 3-year period, from January 1st, 2019 to January 1st, 2023. Radiation doses ranged from 18-24 Gy (single fraction) or 24-27 Gy (3-fraction) for radiosurgery and 30-37.5 Gy for whole brain radiotherapy. Patients were identified that developed RN and VEGF inhibitors were subsequently given to assess effectiveness in the treatment of the condition. We evaluated the dose, frequency, number of treatments received, adverse effects and therapeutic benefits of BEV. Therapeutic benefit was defined as patients that received bevacizumab had a radiological and clinical improvement of the RN (clinical benefit). Brain imaging with MRI or PET/CT scan was completed both pre and post treatment to evaluate efficacy of treatment. Patients were initially given 4 cycles with a subsequent 4 more cycles if it was beneficial and tolerated treatment. Results: 22 patients were included in the study, 9 were males (41%) and median age 66 (range 31-81). 91% (20/22) had a diagnosis of lung cancer. 1 patient had a diagnosis of SCLC, while 19 were diagnosed with NSCLC. The study had a good representation of different races including Non-Hispanic Whites 7 (32%), Hispanics 10 (45%), Blacks 13% (3) and Asians 10% (2). Over 95% (21/22) of patients achieved a clinical benefit, while one patient did not (5%). Patients experienced improvement in cognitive function, headaches, dizziness, weakness, and other symptoms with BEV. MRIs showed improvement in edema and a reduction/stabilization of brain lesions. The most frequent dosing regimen used was BEV 10 mg/kg every two weeks. The median number of cycles given was 4 cycles (1-12). The most common adverse events were hypertension, minor nose bleeding, an occasional protein found in urine. There were no severe AEs or discontinuation of therapy with bevacizumab. Conclusions: This study demonstrated treatment with BEV 10 mg/kg every two weeks for a total of 12 cycles is well tolerated and has potential clinical benefit in RN in lung cancer patients with CNS metastasis. The therapeutic effects of VEGF inhibitors were seen in our small population study but warrants further investigation in a larger population study.
A characteristic comparison of cell-free DNA isolated from plasma and cerebrospinal fluid in patients with cancer.
Authors: Zhang Jian , Wang Wei , Li Yingmei 
Published: June 2023

e14008 Background: Cell-free DNA (cfDNA) from plasma has proved its power as a liquid biopsy analyte in many cancer types, except cancers from central nervous system (CNS). CfDNA from cerebrospinal fluid (CSF) better recapitulates mutations for primary CNS tumors or cancer brain metastasis. The characteristics of cfDNA from plasma, including concentration range, mutation frequency, length, end motif etc. have been thoroughly studied, while the features of cfDNA from CSF are yet to be investigated. Methods: We retrospectively reviewed records since 2021 from a clinical sequencing center, and selected samples from patients with non-small cell lung cancer. CfDNA from 30 CSF and 85 plasma samples was isolated, followed by NGS library preparation procedures, and enriched with a 680-gene panel. Fragmentation features including cfDNA length distribution and frequency of 6-bp end motif sequences were analyzed after removal of UMI. K-means clustering algorithm was utilized to analyze fragment motifs. Results: The mean concentration of cfDNA isolated from plasma and CSF was 13.46 ng/mL (1.28 – 96.40, 95%) and 26.82 ng/mL (2.80-382.00, 95%) respectively. A larger proportion of longer cfDNA fragments (>200bp) in CSF sample was observed, 37.8% in CSF VS 22.8% in plasma. Several end motifs were identified to be highly enriched in either sample type, and we found that sample types could be separated by K-means clustering from top 10 motifs. Conclusions: CSF is a less complicated solution system than plasma, regarding chemical constitutes. The cfDNA length distribution and motif patters are distinguishable in CSF and plasma. Our analysis demonstrated that the characteristics of cfDNA in CSF are obviously different from cfDNA in plasma, and the underlying mechanism remains to be clarified.