tbuckley/cabot-search huggingface dataset:
Genetic Regulation of Atherosclerosis-Relevant Phenotypes in Human Vascular Smooth Muscle Cells
Authors: Redouane Aherrahrou, Liang Guo, V. Peter Nagraj, Aaron Aguhob, Jameson Hinkle, Lisa Chen, Joon Yuhl Soh, Dillon Lue, Gabriel F. Alencar, Arjan Boltjes, Sander W. van der Laan, Emily Farber, Daniela Fuller, Rita Anane-Wae, Ngozi Akingbesote, Ani W. Manichaikul, Lijiang Ma, Minna U. Kaikkonen, Johan L.M. Björkegren, Suna Önengüt-Gümüşcü, Gerard Pasterkamp, Clint L. Miller, Gary K. Owens, Aloke Finn, Mohamad Navab, Alan M. Fogelman, Judith A. Berliner, Mete Civelek
Journal: Circulation Research (2020)

Rationale: Coronary artery disease (CAD) is a major cause of morbidity and mortality worldwide. Recent genome-wide association studies revealed 163 loci associated with CAD. However, the precise molecular mechanisms by which the majority of these loci increase CAD risk are not known. Vascular smooth muscle cells (VSMCs) are critical in the development of CAD. They can play either beneficial or detrimental roles in lesion pathogenesis, depending on the nature of their phenotypic changes. Objective: To identify genetic variants associated with atherosclerosis-relevant phenotypes in VSMCs. Methods and Results: We quantified 12 atherosclerosis-relevant phenotypes related to calcification, proliferation, and migration in VSMCs isolated from 151 multiethnic heart transplant donors. After genotyping and imputation, we performed association mapping using 6.3 million genetic variants. We demonstrated significant variations in calcification, proliferation, and migration. These phenotypes were not correlated with each other. We performed genome-wide association studies for 12 atherosclerosis-relevant phenotypes and identified 4 genome-wide significant loci associated with at least one VSMC phenotype. We overlapped the previously identified CAD loci with our data set and found nominally significant associations at 79 loci. One of them was the chromosome 1q41 locus, which harbors MIA3 . The G allele of the lead risk single nucleotide polymorphism (SNP) rs67180937 was associated with lower VSMC MIA3 expression and lower proliferation. Lentivirus-mediated silencing of MIA3 (melanoma inhibitory activity protein 3) in VSMCs resulted in lower proliferation, consistent with human genetics findings. Furthermore, we observed a significant reduction of MIA3 protein in VSMCs in thin fibrous caps of late-stage atherosclerotic plaques compared to early fibroatheroma with thick and protective fibrous caps in mice and humans. Conclusions: Our data demonstrate that genetic variants have significant influences on VSMC function relevant to the development of atherosclerosis. Furthermore, high MIA3 expression may promote atheroprotective VSMC phenotypic transitions, including increased proliferation, which is essential in the formation or maintenance of a protective fibrous cap.
Characteristics and outcomes of patients (pts) who developed immune-related adverse events (irAEs) with an initial presentation in the emergency department (ED).
Authors: Ryan Holstead, Baskoro Kartolo, Tara D. Baetz
Journal: Journal of Clinical Oncology (2020)

201 Background: Management of irAEs due to immune checkpoint inhibitors (ICIs) requires a high degree of suspicion, and management of severe irAEs require timely initiation of corticosteroids (CS). This can be challenging in the ED, where providers may not be aware of an individual pt’s cancer treatment or its toxicities. Methods: We performed a retrospective single-center chart review for pts treated with ICIs in 2018 and 2019 who subsequently presented to ED. New irAEs with first presentation in ED were analyzed and pt outcomes were recorded. Descriptive statistics compared this population to irAEs identified in outpatient setting, as well as rates of ED utilization in pts on doublet ICI (dICI). Results: Of 351 evaluable pts treated with an ICI, 129 (37%) had at least one presentation to ED. Seventeen pts had a first presentation of a new irAE. These pts had received a median 2 cycles of ICI prior to presentation (interquartile range [IQR] 1-3) Twelve of these pts presented with generalized fatigue or pain, twelve required admission, 4 were admitted to intensive care within 30 days, and two died. Toxicities included hypophysitis (5), arthritis (2), colitis (2), myocarditis (2), neuritis (2), pneumonitis (2), adrenalitis (1), hepatitis (1). Median admission was 8.5 days (IQR 2-32), and median time to corticosteroids was 30.5 hours (range 4-269). Grade 3 or higher toxicity was more frequent in the ED pts compared to the total ICI pt population (70.5% vs. 32.2%). Pts on dICI (n = 41) had a higher rate of ED utilization (n = 23, 56.1%) and ED visits were more likely to be for first presentation of a new irAE (n = 7, 30.4% of dICI ED visits) compared to single-agent ICI regimens. Conclusions: Pts with irAEs that first present at the ED often have generalized symptoms, prolonged hospitalizations, and can have long delays to initiation of CS. Development of a protocolized approach for pts on ICI at the point of care in the ED may improve identification of irAEs, ‘door-to-steroid’ time, and patient outcomes.
Improving the therapeutic index in adoptive cell therapy: key factors that impact efficacy
Authors: Ena Wang, Alessandra Cesano, Lisa H Butterfield, Francesco Marincola
Journal: Journal for ImmunoTherapy of Cancer (2020)

The therapeutic index (TI) is a quantitative assessment of a drug safety proportional to its effectiveness. The estimation is intuitive when the engagement of the product with its target is dependent on stable chemistry and predictable pharmacokinetics as is the case for small molecules or antibodies. But for therapeutics with complex biodistribution and context-dependent potency such as adoptive cell therapy (ACT) products, TI estimations need to consider a broader array of factors. These include product-dependent variability such as functional fitness, unpredictable pharmacokinetics due to non-specific trapping, sequestration and extravasation into normal tissues and variable rates of in vivo expansion. In the case of solid malignancies, additional modifiers dependent on individual tumor immune biology may affect pharmacodynamics, including differential trafficking to benign compared with cancer tissue, hampered engagement with target cells, immune suppression and cellular dysfunction due to unfavorable metabolic conditions. Here, we propose a patient-specific assessment of factors affecting on-tumor from off-tumor activity in disparate immunologic environments that impact ACT’s clinical efficacy and may favorably balance the TI. for ACT products.
An Incidental Uptake of 18F-Choline at PET/CT in Gastric Neuroendocrine Tumor
Authors: Laura Evangelista, Gianluca Cassarino, Decio Capobianco, Michele Povolato, Serena Battista, Marco Rensi
Journal: Clinical Nuclear Medicine (2020)

Abstract We present a case of neuroendocrine tumor localized in the gastric mucosa, incidentally detected by 18 F-choline PET/CT in a 69-year-old man with prostate cancer. 18 F-choline PET/CT scan showed an increased activity in the stomach, later diagnosed as a well-differentiated neuroendocrine tumor, at biopsy. A careful attention of reading 18 F-choline PET/CT images should be made, in order to avoid the missing of potential concomitant neoplasia in patients with prostate cancer.
Utilization of a clinical pathways decision support (CPDS) tool to guide myeloid growth factor usage in metastatic cancer.
Authors: Jeff Dang, Sang Chau, Jessy Delaisla, Andrew Allan Hertler
Journal: Journal of Clinical Oncology (2020)

302 Background: Myeloid growth factors (MGF) are used to prevent and treat febrile neutropenia caused by immunosuppressive therapy. In the curative setting, the use of a full dose-intensity chemotherapy plus an MGF are recommended based on the febrile neutropenic risk levels, as maintaining the full dose intensity has been shown to increase the chance of cure. In the metastatic setting, instead of administering an MGF to maintain dose-intensity, decreasing the dose and/or delaying the chemotherapy to allow recovery of the neutrophils is a reasonable alternative. This is supported by the American Society of Clinical Oncology (ASCO) where a review did not find data to support the use of MGFs to maintain dose-intensity in the treatment of metastatic cancer. In addition, no improvements in disease-free or overall survival were reported for any common cancer with the use of MGFs. New Century Health’s goal is to proactively educate and promote appropriate utilization of MGFs in the metastatic setting by incorporating several non-invasive questions into a Clinical Pathways Decision Support (CPDS) tool that aligns with ASCO’s recommendation (e.g. has a dose reduction/delay been attempted?). Methods: For a Medicare population, approved treatment requests involving the use of chemotherapy in metastatic cancer in the baseline period (baseline: January 2019 to May 2019, n = 606) were compared to requests approved in the implementation period (intervention: June 2019 to November 2019, n = 615). Two states were included in the analyses: Arizona (baseline: n = 200, intervention: n = 237) and Florida (baseline: n = 442, intervention: n = 422). Chi-square ( χ 2 ) tests were performed to evaluate differences in requests during the baseline period as compared to the intervention period. Results: In Arizona, Florida, and total sample, treatment requests for MGF in metastatic cancer were lower in the intervention period as compared to the baseline period (Arizona: 21.52% vs. 28.50%, Florida: 18.48% vs. 23.98%, and total sample: 18.86% vs. 25.25%). In the total sample, the findings suggest that treatment requests for MGF in metastatic cancer were significantly lower in the intervention period as compared to the baseline period (χ 2 = 7.25, p = .007). Conclusions: ASCO recommendations were incorporated into a CPDS tool to help align prescribing behavior. Real world data was used to help evaluate whether this change led a reduction in the utilization of MGFs in metastatic cancer. These findings suggest that such approaches can help guide providers to best practice.
Admission to the ICU in the last 30 days of life and systemic anticancer therapy in the last two weeks of life at Lifespan Cancer Institute (LCI).
Authors: Han You, Don S. Dizon, Nathan Wong, Edward W. Martin, Mary Anne Fenton
Journal: Journal of Clinical Oncology (2020)

214 Background: The ASCO Quality Oncology Practice Initiative identifies ICU admission in the last 30 days and systemic anticancer therapy in the last 14 days of life as indicators of overly aggressive end-of-life care. We sought to delineate clinical factors associated with these indicators. Methods: An IRB approved retrospective chart review was conducted on patients with solid tumors at LCI who died in timepoints ending in January, July and November of 2016 and 2017. Patients were identified through our tumor registry. Patients’ medical records were reviewed for cancer stage, care received, palliative care contact, site of death, ICU admission in last 30 days, and receipt of systemic anticancer therapy (excluding antihormonal therapy) in last 6 months and 2 weeks of life. Results: A total of 250 patients were included in our analysis. 18.8% of LCI patients were admitted to the ICU in the last 30 days of life, 12.8% received systemic anticancer therapy in the last 2 weeks of life, and 19.2% experienced death in the hospital. Significant factors associated with an ICU admission in the last 30 days of life were a diagnosis of lymphoma compared to breast, gynecologic, gastrointestinal, lung, genitourinary, melanoma/carcinoma of unknown primary/head and neck cancer, or other (42.9% vs 20% vs 14.3% vs 9% vs 23.1% vs 25% vs 0% vs 26.3%; P = 0.01), systemic anticancer therapy in last 2 weeks of life (40.6% vs 16.1%; P &lt; 0.005), and age ≤ 45 years at time of metastatic disease compared to age 46-65 or age ≥ 66 (50% vs 15.9% vs 18.1%; P &lt; 0.05). A significant factor associated with systemic anticancer therapy in the last 2 weeks of life was age ≤ 45 years at time of metastatic disease compared to age 46-65 or age ≥ 66 (35.7% vs 16.9% vs 9.4%; P &lt; 0.05). Lastly, a significant factor associated with death in the hospital was lack of palliative care team contact (28.9% vs 15%; P &lt; 0.05). Conclusions: Understanding factors associated with intensive care at the end of life is critical to the provision of value-based cancer care. In this study, a diagnosis of lymphoma, systemic anticancer treatment in the last 2 weeks of life, and age ≤ 45 years at time of metastatic disease were associated with ICU stays in the last 30 days of life. Age ≤ 45 years at time of metastatic disease was associated with systemic anticancer treatment in the last 2 weeks of life, while lack of palliative care involvement was associated with greater chance of death in the hospital. Further understanding of the complex interplay that governs care and decision making at the end of life is required.
Abstract 11518: Blood Pressure Variability Improves With Digital Management Over Usual Care
Authors: Richard V Milani, Jonathan K Wilt, Alexander R Milani, Robert Bober, Eric Malamud, Jonathan Entwisle, Carl J Lavie
Journal: Circulation (2019)

Introduction: Higher systolic blood pressure (SBP) variability (SBPV) has been shown to be a better predictor of all-cause and cardiovascular (CV) mortality, stroke, and cardiac disease compared wi...
Utilisation of artificial intelligence for the development of an EUS-convolutional neural network model trained to enhance the diagnosis of autoimmune pancreatitis
Authors: Neil B Marya, Patrick D Powers, Suresh T Chari, Ferga C Gleeson, Cadman L Leggett, Barham K Abu Dayyeh, Vinay Chandrasekhara, Prasad G Iyer, Shounak Majumder, Randall K Pearson, Bret T Petersen, Elizabeth Rajan, Tarek Sawas, Andrew C Storm, Santhi S Vege, Shigao Chen, Zaiyang Long, David M Hough, Kristin Mara, Michael J Levy
Journal: Gut (2020)

Objective The diagnosis of autoimmune pancreatitis (AIP) is challenging. Sonographic and cross-sectional imaging findings of AIP closely mimic pancreatic ductal adenocarcinoma (PDAC) and techniques for tissue sampling of AIP are suboptimal. These limitations often result in delayed or failed diagnosis, which negatively impact patient management and outcomes. This study aimed to create an endoscopic ultrasound (EUS)-based convolutional neural network (CNN) model trained to differentiate AIP from PDAC, chronic pancreatitis (CP) and normal pancreas (NP), with sufficient performance to analyse EUS video in real time. Design A database of still image and video data obtained from EUS examinations of cases of AIP, PDAC, CP and NP was used to develop a CNN. Occlusion heatmap analysis was used to identify sonographic features the CNN valued when differentiating AIP from PDAC. Results From 583 patients (146 AIP, 292 PDAC, 72 CP and 73 NP), a total of 1 174 461 unique EUS images were extracted. For video data, the CNN processed 955 EUS frames per second and was: 99% sensitive, 98% specific for distinguishing AIP from NP; 94% sensitive, 71% specific for distinguishing AIP from CP; 90% sensitive, 93% specific for distinguishing AIP from PDAC; and 90% sensitive, 85% specific for distinguishing AIP from all studied conditions (ie, PDAC, CP and NP). Conclusion The developed EUS-CNN model accurately differentiated AIP from PDAC and benign pancreatic conditions, thereby offering the capability of earlier and more accurate diagnosis. Use of this model offers the potential for more timely and appropriate patient care and improved outcome.
Evaluation of the Therapeutic Response by 11C-Methionine PET in a Case of Neuro-Sweet Disease
Authors: Katsuya Mitamura, Yuka Yamamoto, Takashi Norikane, Tadayuki Takata, Yoshihiro Nishiyama
Journal: Clinical Nuclear Medicine (2020)

Abstract Sweet disease is a multisystem inflammatory disorder characterized by fever, cutaneous erythematous plaques, and aseptic neutrophilic infiltration of various organs. Neuro-Sweet disease is a known rare central nervous system complication of Sweet disease. A 67-year-old Japanese woman who was diagnosed with neuro-Sweet disease underwent 11 C-methionine ( 11 C-MET) PET. 11 C-MET PET revealed increased accumulation in the affected brain tissues. After steroid therapy, she became asymptomatic, and a follow-up 11 C-MET PET scan showed disappearance of the abnormal uptake of 11 C-MET.
The relationships between rugby union, and health and well-being: a scoping review
Authors: Steffan A Griffin, Nirmala Kanthi Panagodage Perera, Andrew Murray, Catherine Hartley, Samantha G Fawkner, Simon P T Kemp, Keith A Stokes, Paul Kelly
Journal: British Journal of Sports Medicine (2020)

Objective To scope the relationships between rugby union, and health and well-being. Design Scoping review. Data sources Published and unpublished reports of any age, identified by searching electronic databases, platforms and reference lists. Methods A three-step search strategy identified relevant published primary, secondary studies and grey literature, which were screened using a priori inclusion criteria. Data were extracted using a standardised tool, to form (1) a numerical analysis and (2) a thematic summary. Results and discussion 6658 records were identified, and 198 studies met the inclusion criteria. All forms of rugby union can provide health-enhancing physical activity (PA). ‘Non-contact’ and wheelchair rugby in particular provide a wide range of physical and mental health and well-being benefits. The evidence is either mixed or unclear in relation to ‘contact’ rugby union and its effects on a range of physical health domains. Injury and concussion incidence rates are high for contact rugby union relative to other sports. Conclusions A wide range of stakeholders as well as existing and potential participants can use this information to make a more informed decision about participating in and promoting rugby union as a health-enhancing activity. Industry and policy-makers can use this review to inform policies and strategies that look to increase participation rates and use rugby union as a vehicle to contribute positively to population health. Further research understanding rugby union’s contribution to PA as well as to muscle-strengthening and balance is indicated, as well as research examining more health and well-being outcomes across more diverse cohorts.
Utilization of telemedicine to meet the demand throughout the COVID-19 pandemic at a community oncology practice.
Authors: Larry Edward Bilbrey, Susan A Frailley, Stacey L Poole, Cheryl Crouse, Amanda Trader, L. Johnetta Blakely, Luke Frailley, Natalie R. Dickson
Journal: Journal of Clinical Oncology (2020)

263 Background: A large community oncology practice in Tennessee participates in value-based payment arrangements, the success of which depends on close patient monitoring. Telemedicine as an innovative solution was initiated in 2017. The service was limited, due to regulation, licensure requirements, and lack of reimbursement, to survivorship visits, clinical trial consent visits, rural hospital consults and genetic counseling. During the COVID pandemic and loosening of restrictions, telemedicine services were expanded. Methods: We identified a cloud-based platform that allowed patients to use any device with a camera and microphone and required no software downloads. On-line training sessions were provided to clinical staff. All training and workflow implementation were completed in a 2-week time frame. Telemedicine was expanded to include surveillance, urgent care, psychology, palliative care and post-BMT visits as well as new patient consults for medical, radiation and gynecologic oncology patients. Patient satisfaction surveys were administered. Results: Our telemedicine visits increased weekly beginning March 1, peaking in the month of April with an average of 77 scheduled telemedicine visits per day across the practice. During the month of April, our practice saw a record clinical trial accrual in our Phase-1 Drug Development Unit with a 22% increase over the previous average. Patients who responded to a satisfaction survey were highly satisfied with the telemedicine visit with a 73% positive response rate. Nearly half of our eligible patients did not have the technology or broad-band access to be able to participate in telemedicine. Conclusions: Our prior experience with telemedicine, though limited, facilitated the development of an infrastructure that provided adequate number of devices and internet bandwidth capacity to support rapid expansion of telemedicine. We were able to maintain high quality care and access to clinical trials during the pandemic and see the value of this service long-term. We hope to add tele-pharmacy and care coordination services. Political leadership and patient advocacy groups should explore ways to ensure that all patients may benefit from this technology, especially those in under-served areas.
A pilot study of risk stratification and outreach to hematology/oncology patients during the COVID-19 pandemic.
Authors: Chelsea K. Osterman, Tammy Triglianos, Gary Winzelberg, Angela Nichols, Julia Rodriguez-O'Donnell, Sharon M Bigelow, Hendrik Van Deventer, Hanna Kelly Sanoff, Emily Miller Ray
Journal: Journal of Clinical Oncology (2020)

211 Background: Cancer patients have many medical and psychosocial needs, which may increase during the coronavirus pandemic and may be difficult to identify or address in the absence of in-person patient visits. We sought to (1) risk stratify hematology/oncology patients using general medicine and cancer-specific methods to identify those at high risk for acute care utilization, (2) measure the correlation between risk-stratification methods, and (3) perform a phone-based needs assessment with intervention for these patients. Methods: Patients were risk-stratified using a general medical health composite score (HCS) embedded in the electronic medical record, and a cancer-specific risk (CSR) stratification based on disease and treatment characteristics. The correlation between HCS and CSR was measured using Spearman’s correlation. A multi-disciplinary team developed a focused needs assessment script with recommended interventions for patients categorized as high-risk by either method. The number of patient needs identified and referrals for services made in the first month of outreach are reported. Results: 1,421 patients were risk stratified, with 15% high-risk using HCS and 21.2% high-risk using CSR. Overall correlation between HCS and CSR was modest (r = 0.39). During the first month of the pilot, 287 patients were called for outreach with 245 contacted (85%). Commonly identified needs were financial difficulties (17%), uncontrolled symptoms (15%), and interest in advance care planning (13%), resulting in referral for supportive services for 33% of patients. Conclusions: There is a high burden of unmet medical and psychosocial needs in hematology/oncology patients during the coronavirus pandemic. A phone-based outreach program results in identification of and intervention for these needs, however additional cancer-specific risk models are needed to improve targeting to high-risk patients. This process can serve as a framework for other institutions wishing to implement similar outreach programs during this pandemic. [Table: see text]