tbuckley/cabot-search huggingface dataset:
Assessing the roles of inflammation and blood brain barrier permeability in cognitive impairment: A nationwide longitudinal study of patients receiving chemotherapy and non-cancer controls.
Authors: Elizabeth Belcher, Nikesha Gilmore, Amber Kleckner, Ian Kleckner, Eva Culakova, Louis Lotta, Bryan Thompson, Jodi Geer, Judith O. Hopkins, Joan Long, Michelle Christine Janelsins
Journal: Journal of Clinical Oncology (2020)

12070 Background: Cognitive impairment is a prevalent side effect of chemotherapy. We have previously shown that chemotherapy treatment is associated with worse performance on the Rapid Visual Processing test (RVP), an objective measure of sustained attention, over time compared to non-cancer controls. Better understanding of the biologic mechanisms underlying cognitive impairment in cancer patients is needed. The pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) has been implicated in increasing blood brain barrier (BBB) permeability, which in turn is associated with cognitive impairment. This study assessed the relationships of TNFα and S100β, a biomarker of BBB permeability, to each other and to RVP performance over time. Methods: We analyzed a subset of participants (n = 89 patients, n = 52 controls, mean age = 60) from a prospective longitudinal study of women with breast cancer receiving chemotherapy and non-cancer controls. TNFα and S100β were measured in serum pre-chemotherapy (T1, ≤7 days before first treatment) and post-chemotherapy (T2, ≤1 month after last treatment) and at corresponding times for controls. Sustained attention was assessed by total correct rejections on the RVP test at T1 and T2. Separate linear regression models including all participants were used to relate 1) baseline TNFα and S100β levels to change in RVP performance over time, 2) change in TNFα and S100β to change in RVP performance over time, and 3) change in TNFα to change in S100β. Models were adjusted for age. 4) T-tests were used to compare the TNFα and S100β change scores (T1 to T2) of patients vs controls. Results: Greater increase (T1 to T2) in the pro-inflammatory cytokine TNFα was associated with worse cognition, measured by performance on RVP over time (p = 0.02). Higher baseline S100β, a biomarker of BBB permeability, was associated with worse performance on RVP over time (p = 0.09). Increase in TNFα was associated with increase in S100β (p = 0.11). S100β increased from T1 to T2 in patients relative to controls (p = 0.09). Conclusions: These results suggest that higher TNFα may be related to increases in blood brain barrier permeability and worse cognition. Future studies will further define the link between inflammation, blood brain barrier permeability and chemotherapy-related cognitive decline, with the goal of informing the development of new interventions. Funding: R01CA231014, T32CA102618, DP2CA195765, UG1CA189961.
Abstract 10195: Prediminance of Th1 and Th17 During Myocardial Infarction in Sr-bi Ko/apoer61h/h Mice
Authors: Hiroyasu Inui, Makoto Nishida, Jo Kyuyou, Zhu Yinghong, Kanno Kotaro, Takeshi Okada, Ohama Toru, Masahiro Koseki, Sakata Yasushi, Yamashita Shizuya
Journal: Circulation (2019)

Introduction: We have examined the process of myocardial infarction in SR-BI KO/ApoeR61h/h mice which is a valuable, high-fat-diet (HFD) induced myocardial infarction model mice (Plos One. 2013, J ...
Results of a first-in-human phase I study of SRF231, a fully human, high-affinity anti-CD47 antibody.
Authors: Amita Patnaik, Anna Spreafico, Alison M. Paterson, Marisa Peluso, Jou-Ku Chung, Beth Bowers, Demi Niforos, Alison M. O'Neill, Muralidhar Beeram, Marco Iafolla, Julia Lester, Alison M. Schram
Journal: Journal of Clinical Oncology (2020)

3064 Background: CD47 is a transmembrane protein that acts as a “Don’t Eat Me” signal to evade immune recognition. It is overexpressed in multiple cancer subtypes and is associated with poor prognosis. SRF231 is an investigational, fully human, high-affinity CD47-targeting antibody that delivers an activating signal to myeloid cells and displays favorable preclinical characteristics regarding its receptor occupancy/tumor exposure/efficacy relationship. Methods: In a Phase 1 study, SRF231-101 (NCT03512340), patients with advanced solid and hematologic malignancies who had failed standard therapy were enrolled in dose escalation cohorts (accelerated single-patient followed by standard 3+3) to establish the preliminary safety of SRF231 as a monotherapy and identify a dose and schedule suitable for expansion. In addition to collection of safety data, clinical outcomes were evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and SRF231 pharmacokinetic (PK) and pharmacodynamic (receptor occupancy) analyses were performed. Results: As of January 11, 2020, a total of 46 patients were enrolled, 25 in every-3-week intravenous (IV) dosing schedules and 21 in weekly IV dosing schedules. Weekly dosing schedules also explored the use of a 1.0 mg/kg initiation dose. Other than one patient with recurrent follicular lymphoma, all patients had recurrent/refractory solid tumors. The most common treatment emergent adverse events across dosing schedules were low-grade fatigue (43%), headache (35%), and pyrexia (30%). On every-3-week dosing schedules, 2 dose-limiting toxicities (DLTs) were observed: Grade 3 febrile neutropenia and Grade 3 hemolysis, both at a 12.0 mg/kg dose level. On weekly dosing schedules, 3 DLTs were observed: Grade 4 thrombocytopenia (6.0 mg/kg), Grade 4 amylase and lipase increased (4.0 mg/kg with initiation dose), and Grade 3 fatigue (4.0 mg/kg). The maximum tolerated dose was 9.0 mg/kg on an every-3-week and 4.0 mg/kg on a weekly schedule. Receptor occupancy was maintained at &gt; 90% throughout the dosing period with a 4.0 mg/kg weekly dose schedule. Out of 37 patients who were response evaluable by RECIST, there were no complete or partial responders, although prolonged stable disease has been observed. Conclusions: Preliminary data from a Phase 1 study of SRF231, an anti-CD47 antibody, demonstrate that SRF231 may be administered safely and doses of 4.0 mg/kg weekly maintain &gt; 90% receptor occupancy throughout the dosing period. Updated safety data, clinical outcomes, and PK/pharmacodynamic data will be presented. Clinical trial information: NCT03512340 .
Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the <scp>C</scp>ardio‐<scp>O</scp>ncology <scp>S</scp>tudy <scp>G</scp>roup of the <scp>H</scp>eart <scp>F</scp>ailure <scp>A</scp>ssociation of the <scp>E</scp>uropean <scp>S</scp>ociety of <scp>C</scp>ardiology in collaboration with the <scp>I</scp>nternational <scp>C</scp>ardio‐<scp>O</scp>ncology <scp>S</scp>ociety
Authors: Alexander R. Lyon, Susan Dent, Susannah Stanway, Helena Earl, Christine Brezden‐Masley, Alain Cohen‐Solal, Carlo G. Tocchetti, Javid J. Moslehi, John D. Groarke, Jutta Bergler‐Klein, Vincent Khoo, Li Ling Tan, Markus S. Anker, Stephan von Haehling, Christoph Maack, Radek Pudil, Ana Barac, Paaladinesh Thavendiranathan, Bonnie Ky, Tomas G. Neilan, Yury Belenkov, Stuart D. Rosen, Zaza Iakobishvili, Aaron L. Sverdlov, Ludhmila A. Hajjar, Ariane V.S. Macedo, Charlotte Manisty, Fortunato Ciardiello, Dimitrios Farmakis, Rudolf A. de Boer, Hadi Skouri, Thomas M. Suter, Daniela Cardinale, Ronald M. Witteles, Michael G. Fradley, Joerg Herrmann, Robert F. Cornell, Ashutosh Wechelaker, Michael J. Mauro, Dragana Milojkovic, Hugues de Lavallade, Frank Ruschitzka, Andrew J.S. Coats, Petar M. Seferovic, Ovidiu Chioncel, Thomas Thum, Johann Bauersachs, M. Sol Andres, David J. Wright, Teresa López‐Fernández, Chris Plummer, Daniel Lenihan
Journal: European Journal of Heart Failure (2020)
Chemotherapy-induced peripheral neuropathy as a predictor of neuropathic pain in breast cancer patients previously treated with paclitaxel
Authors: C. C. Reyes-Gibby, P. Morrow
Journal: Journal of Clinical Oncology (2009)

e20505 Background: Neuropathic pain (NP) remains difficult to control for a significant proportion of patients with cancer. Chemotherapy induced peripheral neuropathy (CIPN) is postulated as an initial stage to the development of NP. Among breast cancer patients, taxanes, platinum agents, and vinca alkaloids are most likely to cause NP. The purpose of this study was to assess the extent to which those who experienced CIPN (NCI toxicity criteria ≥ grade 2 sensory neuropathy) during paclitaxel chemotherapy were at risk of developing chronic NP, controlling for disease- and treatment-related variables (e.g., stage of disease, location of tumor chemotherapy and other cancer therapies, dose of chemotherapy and duration of treatment), clinical health status (e.g., comorbid conditions), and sociodemographic characteristics (e.g., age, race). Methods: We conducted a follow-up survey of breast cancer patients who previously participated in clinical trials for paclitaxel. Patients were asked if they have ever been diagnosed by the physician or healthcare provider for NP during the survey. Clinical trial data (NCI Toxicity, cummulative dose) were abstracted from a clinical database. Results: Of the 430 potential respondents, 240 responded to the survey. Mean follow-up time was 9.5 years (SD=2.1). Sixty three percent of the respondents had grade 2 or greater sensory neuropathy during their previous treatment with paclitaxel. Follow-up data showed that 18% (43/240) were subsequently diagnosed by their physician to have NP. Logistic regression analysis showed that those with CIPN during the trial were 3 times more likely to having been diagnosed with NP (OR=3; 95%CI=1.2; 7.2; p&lt;0.001), which persisted in the multivariable model. Other variables found to be associated with NP included cummulative dose of paclitaxel, and comorbid conditions such as diabetes and osteoarthritis. Patients with NP reported twice as many visits to their health care provider (p=0.028); had taken more prescription (50% versus 19%; p=0.0001) for pain relative to those without NP. Conclusions: We provide empirical evidence on the importance CIPN as a risk factor for NP in breast cancer patients.Prospective studies with larger cohorts are needed to validate our findings. No significant financial relationships to disclose.
坚持院办院管的社区卫生服务管理体制
Authors: 江捍平, 罗乐宣, 李创, 张英姬, 陈皞璘, 赖光强
Journal: BMJ (2011)

深圳市有607个社区健康服务中心(简称社康中心,即社区卫生服务中心),均由医院作为法人机构举办,这些社康中心与一级医院、门诊部、诊所、医务室一起,构成本市社区15分钟医疗服务圈.每个社康中心平均面积629 km2,医务人员平均10.23人,平均服务人口2.3万人,服务半径平均为3.5 km2,以灵活、快捷、方便的服务模式受到广大基层群众的欢迎。
Overcoming clinical trial accrual barriers at UPMC: A successful experience.
Authors: Vincent Edgar Reyes, Terry L. Evans, Robert Alan VanderWeele, Christopher Ritchie Marsh, Sajid M. Peracha, Gauri J. Kiefer, Nishant Tageja, Rushir J. Choksi, Bhanu Pappu, Antoinette J. Wozniak, Robert L. Ferris, Stanley M. Marks
Journal: Journal of Clinical Oncology (2020)

e14152 Background: UPMC Hillman Cancer Center Medical Oncology Network is one of the largest integrated community oncology network in the United States. A large gap exists between trial participation rates and the willingness of patients and physicians. There are numerous barriers to clinical trial accrual in the medical oncology community. UPMC identified and created solutions to overcome barriers, and thus dramatically increase clinical trial accrual in 2019. Methods: A physician led advisory board was created to identity problems and find solutions to increase clinical trial accrual in the community. Processes that were implemented in the community to increase physician engagement included identifying more community friendly clinical trials, highlighting high impact clinical trials, and reprioritizing available clinical trials. Also, community physician champions were selected and directly linked with the academic faculty by disease site at UPMC Hillman Cancer Center. Other marketing tools were utilized like a newly developed mobile clinical trial app, community physician dedicated clinical trial retreat, and clinical trial newsletter. High volume community sites were identified as flagship clinical trial accrual centers. Results: With the implementation of physician led initiatives, total (interventional + non interventional) clinical trial accrual increased in the UPMC medical oncology network from 216 in 2018 to 660 in 2019. In 2019 there were 631 interventional trial accruals and 363 therapeutic trial accruals. In 2018 there were only 186 interventional trial accruals and 46 therapeutic trial accruals. Conclusions: The community oncology-directed initiatives created a culture change among the community physicians. UPMC implemented new processes in the medical oncology network that significantly increased clinical trial accrual. [Table: see text]
The imaging substudy of the randomized ARTE trial: MRI and 18FET PET associations with overall survival benefit from bevacizumab in elderly patients with newly diagnosed IDH wildtype glioblastoma.
Authors: Hans-Georg Wirsching, Ulrich Roelcke, Jonathan Weller, Thomas Hundsberger, Andreas Felix Hottinger, Roger Anton Fredy Von Moos, Francesca Caparrotti, Katrin Lisa Conen, Luca Remonda, Patrick Roth, Adrian Ochsenbein, Ghazaleh Tabatabai, Michael Weller
Journal: Journal of Clinical Oncology (2020)

2520 Background: Bevacizumab failed to demonstrate overall survival benefit despite markedly prolonged progression-free survival in glioblastoma patients. Reasons for this divergence may include suboptimal patient selection and delayed diagnosis of progression on MRI scans under bevacizumab. Imaging analyses of retrospective and uncontrolled clinical trial cohorts suggest MRI diffusion mapping as a predictor of benefit from bevacizumab. Moreover, amino acid PET has been proposed by the RANO working group for the differentiation of tumor versus edema or gliosis based on proof-of-principle studies demonstrating earlier detection of progression with PET compared to MRI. Methods: ARTE (NCT01443676) was a 2:1 randomized, multi-center, open-label trial of hypofractionated radiotherapy in combination with intravenous bevacizumab every 2 weeks (BEV/RT) versus RT alone in patients with newly diagnosed glioblastoma aged 65 years or older. Patients with histologically and molecularly confirmed IDH wildtype glioblastoma aged 65 years or older were analyzed. MRI was available from 67 and serial 18 FET PET from 30 patients in this post hoc analysis. 18 FET PET intensity ratios and herein reported MRI parameters including tumor volumetric analyses and ADC were analyzed blinded for outcome and study arm. Results: Demographic, clinical and molecular parameters were balanced between treatment arms. Overall survival benefit from bevacizumab was observed for larger contrast-enhancing tumor volumes (hazard ratio [HR] per cm 3 0.94, 95% CI 0.89-0.99, p = 0.032) and higher ADC (HR 0.18, 95% CI 0.05-0.66, p = 0.025) on pre-treatment MRI. Response in the BEV/RT arm by the standard MRI-based RANO criteria was associated with overall survival by trend (HR 0.56, 95% CI 0.30-1.10, time-dependent p = 0.094). In a multivariate model controlling for established risk factors, 18 FET tumor-to-brain uptake ratios (TBR) of non-contrast-enhancing tumor portions predicted inferior overall survival specifically in the BEV/RT arm (HR [per 0.1 18 FET TBR] 1.50, 95% CI 1.05-2.13, time-dependent p = 0.025). Controlling for 18 FET TBR at first follow-up identified benefit from BEV/RT by trend (HR 0.41, 95% CI 0.16-1.07, p = 0.069). Conclusions: Large contrast-enhancing tumor mass and high ADC identify patients with overall survival benefit from bevacizumab. Under bevacizumab, non-contrast enhancing tumor portions can be adequately monitored by amino acid PET.
A randomized controlled trial (RCT) testing a mobile application (app) to identify cancer treatment-related financial assistance.
Authors: Aaron Tarnasky, George Nhat Tran, Jonathan Nicolla, Fred Andrew Paul Friedman, Steven Wolf, Jesse D Troy, Anthony Derek Sung, Kanan Shah, Jakob Oury, Jillian C Thompson, Ben Gagosian, Kathryn I. Pollak, Ian Manners, Yousuf Zafar
Journal: Journal of Clinical Oncology (2020)

7073 Background: Insured cancer patients face high treatment-related, out-of-pocket costs. While philanthropic- and pharmaceutical-sponsored financial assistance programs exist, patients are often unaware of them. We developed “Bridge”, a patient-facing app that identified financial assistance programs for which a patient might be eligible based on treatment, disease, insurance, and financial characteristics. We hypothesized that patients in the Bridge study arm would be more likely than controls to apply for and receive financial assistance. Methods: We enrolled patients at a single institution from January 2018-March 2019. Patients were receiving treatment for any cancer, had a life expectancy of ≥6 months, and self-reported out-of-pocket costs. We randomized patients 1:1 to intervention (Bridge) vs. control (financial assistance educational websites). We assessed subjective financial distress with the validated COST measure. Outcomes included application for and receipt of financial assistance. Data on outcomes was collected from the medical record, institutional pharmacy database, and Bridge. We compared patient characteristics between study arms using chi-square and Mann-Whitney-Wilcoxon tests. We used an unadjusted logistic regression model to compare differences in outcomes. Results: We randomized 200 patients and found no significant differences between arms in baseline characteristics (Table). At 6 months from enrollment, patients in the Bridge arm were more likely than controls to apply for financial assistance [35% Bridge vs. 10% control, OR 3.53, 95%CI 1.69-7.34, p &lt; 0.01]. Bridge patients were also more likely than controls to receive financial assistance (30% Bridge vs. 9% control, OR 3.39, 95%CI 1.78-6.46, p &lt; 0.01). Conclusions: Among patients with treatment-related out-of-pocket costs, those who interacted with a financial assistance app were significantly more likely to apply for and receive treatment-related financial assistance. [Table: see text]
Lung cancer gender differences: An analysis of 1599 patients diagnosed between 1996 and 2018.
Authors: Sharareh Seifi, Adnan Khosravi, Babak Salimi, Zahra Esfahani Monfared
Journal: Journal of Clinical Oncology (2020)

e13596 Background: Several studies showed disparities in terms of gender in lung cancer pattern. As we know, there is limited available data from lung cancer trends by gender in Iran and information reported in previous Iranian studies has become outdated. Methods: This observational study included data of Lung Cancer which were obtained from National Institute of Tuberculosis and Lung Disease (NRITLD), Masih Daneshvari Hospital,from January 1, 1996 to June 1, 2018. Overall survival (OS) and progression free survival (PFS) were estimated for each gender at several time points by the Kaplan-Meier method. Results: Characteristics of 1599 patients are shown in Table. Adenocarcinoma was most prevalent pathology in both sex and incidence of this histology increased in men during all study periods except 2002-2006. Notably, Adenocarcinoma has an increasing pattern especially after 2006 in women. Most prevalent Stage was advanced stages in both sex. Mean OS were 9.84±0.56 and 10.27±0.91 months in male and female respectively (P = 0.769). Also, mean PFS was non-significantly longer in men than women (7.6±0.49 vs 7.4±0.39, P = 0.903).Cox regression multivariate analysis showed only significant effect for advanced/extensive stages on OS(P = 0.015). Conclusions: The findings highlight important characteristics of the lung cancer epidemic; women are diagnosed at younger age and were less smoker than men. It is necessary for all chealthcare systems to assess the cancer burden periodically and gender differences should be considered for screening guidelines, preventive strategies, and Treatment. [Table: see text]
Prediction of lymph node metastasis using 5-point visual scale criteria of [18F]-fluoro-2-deoxy-D-glucose on positron emission tomography / computed tomography for early stage lung adenocarcinoma.
Authors: Atsushi Kagimoto, Yasuhiro Tsutani, Yoshinori Handa, Takahiro Mimae, Yoshihiro Miyata, Morihito Okada
Journal: Journal of Clinical Oncology (2020)

e21084 Background: This study aimed to investigate the efficacy of the Deauville criteria, a 5-point visual scale criteria to assess the maximum standardized uptake value (SUVmax) of [18F]-fluoro-2-deoxy-D-glucose (FDG) on positron emission tomography (PET)/computed tomography (CT), in predicting lymph node metastasis and other pathological invasive characteristics of early-stage lung adenocarcinoma. Methods: In this retrospective study including 453 patients undergoing lobectomy or segmentectomy with lymph node dissection for clinical N0 lung adenocarcinoma with a whole size ≤ 3 cm between April 2011 and March 2019, the FDG-PET/CT scans were evaluated using the Deauville criteria to analyze the relationship of Deauville score with the clinicopathological characteristics and prognosis.The scoring method was as follows: Deauville score of 1, no FDG uptake by the primary tumor (same as background); Deauville score of 2, tumor FDG uptake that is the same as or weaker than that of mediastinum; Deauville score of 3, tumor FDG uptake that is stronger than that of mediastinum but same as or weaker than that of liver; Deauville score of 4, tumor FDG uptake that is moderately higher than that of liver; Deauville score of 5, tumor FDG uptake that is markedly stronger than that of liver. Results: The lymph node metastases were present in 0 (0%), 2 (1.1%), 6 (9.5%), 6 (15.8%), and 13 (15.7%) patients with Deauville scores of 1, 2, 3, 4 and 5, respectively. The pathological invasive characteristics (lymphatic, vascular, or visceral pleural invasion) were detected in 2 (2.4%), 17 (9.9%), 18 (28.6%), 23 (60.5%), and 54 (65.1%) patients, respectively. Similar results were found when the study cohort was analyzed according to the institutions where the FDG-PET/CT scans were performed. The 3-year recurrence-free survival was longer in the patients with a Deauville score of 1–2 (97.2%) than those with a Deauville score of 3 (86.2%, p &lt; 0.001) or 4–5 (80.7%, p &lt; 0.001). Conclusions: The 5-point-scale evaluation of the SUVmax on FDG-PET/CT using the Deauville score was useful in predicting not only lymph node metastasis but also other malignancy characteristics of early-stage lung adenocarcinoma.
一次性输血器在胸腔穿刺术中的应用
Authors: 蒋毅, 朱清, 昂春臣, 赵宏
Journal: BMJ (2005)

传统的胸腔穿刺针针尾连接着橡皮胶管,以便和注射器相连.在临床应用中,我们体会有如下不足之处:①橡皮胶管口径大,和注射器连接不严密;②穿刺过程中,如需排空注射器时要先用止血钳夹闭橡皮胶管,不方便;③穿刺针尖进入胸膜腔多是以针尖的抵抗感突然消失为标志,有时其抵抗感的变化不明显;④穿刺针重复消毒使用,有造成交叉感染的可能.因此,我们将一次性输血器用于胸腔穿刺术,不但克服了上述不足,也有其自身优越性。