tbuckley/cabot-search huggingface dataset:
Assessment of Routine Esophagram for Detecting Anastomotic Leak After Esophagectomy
Authors: Kelly R. Haisley, Missy L. DeSouza, Elizabeth N. Dewey, Sabrina E. Drexel, Yalini Vigneswaran, John G. Hunter, James P. Dolan
Journal: JAMA Surgery (2019)

This study assesses the value of routine esophagrams in detecting anastomotic leaks after esophagectomy.
Preliminary results in colorectal cancer (CRC) patients enrolled in the GATTO study, a phase I study of Tomuzotuximab in combination with Gatipotuzumab in patients with EGFR positive solid tumors
Authors: E. Garralda, W. Fiedler, I. Matos, C. Rolling, M. Kebenko, K. Klinghammer, G. Conte, F. Raspagliesi, B. Habel, H. Baumeister, S. Ochsenreither, A. Zurlo
Journal: Annals of Oncology (2019)
Oxidative stress as candidate therapeutic target to overcome microenvironmental protection of CLL
Authors: Deyan Yordanov Yosifov, Irina Idler, Nupur Bhattacharya, Michaela Reichenzeller, Viola Close, Daria Ezerina, Annika Scheffold, Billy Michael Chelliah Jebaraj, Sabrina Kugler, Johannes Bloehdorn, Jasmin Bahlo, Sandra Robrecht, Barbara Eichhorst, Kirsten Fischer, Anja Weigel, Hauke Busch, Peter Lichter, Hartmut Döhner, Tobias P. Dick, Stephan Stilgenbauer, Daniel Mertens
Journal: Leukemia (2019)
A combination phase I study of biweekly docetaxel and 5’-DFUR in patients with unresectable or recurrent gastric cancer
Authors: S. Yoshino, M. Oka, S. Hazama, R. Shimizu, T. Yamamoto
Journal: Journal of Clinical Oncology (2006)

14115 Background: Docetaxel (DOC) and 5’-DFUR (an intermetamolite of capecitabine) have single-agent activity in gastric cancer and have distinct mechanisms of action and no overlap of key toxicities. Synergistic interaction between DOC and 5’-DFUR is mediated by taxane-induced up-regulation of thymidine phosphorylase. The objectives of this study were to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT) and the recommended dose (RD) of the combination therapy of biweekly DOC and 5’-DFUR. The DLT was set in low grade to treat the patients in the outpatient clinic. Methods: Eligibility criteria included patients with histologically proven unresectable or recurrent gastric cancer, no requirement of prior chemotherapy, a performance status of 0–2, adequate organ function and written informed consent. DOC was administered by 1-hour intravenous infusion (level 1, 2, 3, 4: 30, 35, 40, 45 mg/m 2 ) biweekly for 4 weeks. 5’-DFUR was administered orally at a fixed dose of 600mg/body everyday. Toxicity and efficacy were evaluated during the 2 cycles for 8 weeks. Three or 6 patients were enrolled at each dose level. Administration of DOC was skipped in the event of grade 2 hematologic toxicity. DLT was defined as grade 3 hematologic toxicity, grade 2 non-hematologic toxicity. The MTD was defined as the dose level at which at least two of three patients or three of six patients presented with DLT. Results: Twelve patients with a median age of 58 years (range, 29 to 75) were enrolled in this study. Five patients have received prior chemotherapy. Eight patients were unresectable and 4 had recurrent tumors. At level 1 (n=3), 2 (n=3), 3 (n=3), no patients developed DLT. Two patients developed DLT at level 4 (n=3). All DLT was neutropenia. Only 1 developed grade 4 neutropenia at level 4. Non-hematological toxicity was uncommon. Level 4 was determined as the MTD. Of 8 evaluable patients, responses included 4 PR, 3 SD and 1 PD for an overall response rate of 50%. Conclusions: The MTD of DOC in this combination is 45 mg/m 2 and the RD is 40 mg/m 2 . This regimen is well-tolerated with high response rate in outpatient setting. A phase II study is necessary to evaluate the response of this regimen. No significant financial relationships to disclose.
Comparison of care patterns for hospitalized immune-related adverse events (irAEs) between melanoma patients on combination immune checkpoint inhibitor (ICI) therapy versus ICI monotherapy.
Authors: RuiQui Chen, Elliot Charles Smith, Sze Wah Samuel Chan, Katrina Hueniken, M. Catherine Brown, Habeeb Majeed, Kendra Ross, Diana Gray, Wei Xu, David Hogg, Srikala S. Sridhar, Adrian G. Sacher, Natasha B. Leighl, Monika K. Krzyzanowska, Marcus O. Butler, Geoffrey Liu, Lawson Eng
Journal: Journal of Clinical Oncology (2019)

85 Background: Prior clinical trials in melanoma have demonstrated higher rates of irAEs from combination ICI therapy compared to monotherapy. However, this has not been well studied in the real-world where patients often have greater co-morbidities and less organ reserve. We aim to compare irAEs hospitalizations for melanoma patients on combination vs monotherapy ICIs. Methods: We performed a single centre retrospective chart review (Princess Margaret Cancer Centre, Toronto, ON) for all melanoma patients receiving ICI as standard of care (2012-2017) admitted with irAEs. Data collected include demographics, investigations, management and outcomes of hospitalizations. Descriptive analyses were performed to characterize hospitalizations and compare between ICI combination vs monotherapy groups. Results: Among 381 melanoma patients identified on standard of care ICI, 41 (11%) were admitted for irAE. Among those admitted, 10% received monotherapy with nivolumab, 22% pembrolizumab, 39% ipilimumab and 29% combination ICI. Admission rates were higher among patients receiving combination ICI compared to monotherapy (20% vs 8% p = 0.003). Prevalence of the most common irAEs were similar between combination and monotherapy groups: colitis (58% vs 59%), pneumonitis (8% vs 14%) and hepatitis (8% vs 10%). Less than half received invasive diagnostic tests (i.e, endoscopy) (42% combination vs 35% monotherapy, p = 0.50) with 3 (60%) and 5 (50%) confirming irAEs, respectively. Rates of infliximab use were similar between the combination and monotherapy group (25% vs 21%, p = 0.70). Average length of stay was shorter for patients on combination ICI compared to monotherapy (5 days vs 15 days, p = 0.08). irAE readmission rates were similar between patients receiving combination ICI compared to monotherapy (20% vs 17%, p = 0.65). Conclusions: Despite higher admission rates among patients receiving combination ICI, there was a trend towards shorter hospitalizations. Other outcomes including diagnoses, investigations and management were not significantly different between patients receiving combination vs ICI monotherapy.
Isolated Muscular Sarcoidosis Revealed by Hypercalcemia and 18F-FDG PET/CT
Authors: Anthony Dhomps, Thibault Foret, Nathalie Streichenberger, Andrea Skanjeti, Jeremie Tordo
Journal: Clinical Nuclear Medicine (2019)

Abstract A 43-year-old woman, with previous history of renal lithiasis, was admitted on an emergency for severe hypercalcemia fortuitously discovered in a context of rapidly progressive kidney failure. An 18 F-FDG PET/CT performed to rule out underlying malignancy revealed an intense diffuse and isolated muscular FDG uptake with fascia infiltration on the CT finding. A muscular biopsy was performed and demonstrated a non-necrosing granuloma with multinucleated giant cells consistent with muscular sarcoidosis. A corticotherapy was started with a rapid normalization of serum calcium level. The follow-up 18 F-FDG PET/CT 4 months later showed a complete response of the sarcoidosis myositis.
Effect of solution condition on hydroxyapatite formation in evaluating bioactivity of B2O3 containing 45S5 bioactive glasses
Authors: Xiaonan Lu, Jessica Kolzow, Roberto R. Chen, Jincheng Du
Journal: Bioactive Materials (2019)

The effects of testing solutions and conditions on hydroxyapatite (HAp) formation as a means of in vitro bioactivity evaluation of B2O3 containing 45S5 bioactive glasses were systematically investigated. Four glass samples prepared by the traditional melt and quench process, where SiO2 in 45S5 was gradually replaced by B2O3 (up to 30%), were studied. Two solutions: the simulated body fluid (SBF) and K2HPO4 solutions were used as the medium for evaluating in vitro bioactivity through the formation of HAp on glass surface as a function of time. It was found that addition of boron oxide delayed the HAp formation in both SBF and K2HPO4 solutions, while the reaction between glass and the K2HPO4 solution is much faster as compared to SBF. In addition to the composition and medium effects, we also studied whether the solution treatments (e.g., adjusting to maintain a pH of 7.4, refreshing solution at certain time interval, and no disturbance during immersion) affect HAp formation. Fourier transform infrared spectrometer (FTIR) equipped with an attenuated total reflection (ATR) sampling technique and scanning electron microscopy (SEM) were conducted to identify HAp formation on glass powder surfaces and to observe HAp morphologies, respectively. The results show that refreshing solution every 24 h produced the fastest HAp formation for low boron-containing samples when SBF was used as testing solution, while no significant differences were observed when K2HPO4 solution was used. This study thus suggests the testing solutions and conditions play an important role on the in vitro bioactivity testing results and should be carefully considered when study materials with varying bioactivities.
Clinical relevance of circulating CK-19 mRNA-positive cells detected during the period of adjuvant tamoxifen treatment in patients with early breast cancer
Authors: N. Xenidis, V. Markos, S. Apostolaki, M. Perraki, A. Pallis, G. Sfakiotaki, M. Kafousi, E. Stathopoulos, S. Kakolyris, D. Mavroudis, V. Georgoulias
Journal: Journal of Clinical Oncology (2007)

10534 Background: To evaluate the effect of adjuvant treatment with tamoxifen on the CK-19 mRNA+ circulating tumor cells (CTCs) in patients with early-stage breast cancer. Methods: CTCs were prospectively and longitudinally detected using a specific real-time PCR for CK-19 mRNA in 119 patients with estrogen and/or progesterone receptor-positive tumors during the period of tamoxifen administration. Results: Twenty-two (18.5%) patients had detectable CK-19 mRNA+ CTCs after the completion of adjuvant chemotherapy and in 15 (68.2%) of them adjuvant tamoxifen could not eliminate these cells (persistently positive). In 68 (57.1%) patients no CK-19 mRNA+ CTCs could be detected throughout the follow up period (persistently negative). Seven (46.7%) of the 15 persistently positive and six (8.8%) of the 68 persistently negative patients developed disease recurrence (p=0.00026). Persistence of CK-19 mRNA+ CTCs was associated with a significantly shorter median disease-free interval (p=0.0001) and overall survival (0.0005). Multivariate analysis revealed that the detection of CK-19 mRNA+ CTCs during the administration of tamoxifen was associated with an increased risk of relapse (HR=22.318, p=0.00006) and death (HR=13.954, p&lt; 0.00001). Conclusions: The detection of CK-19 mRNA+ CTCs throughout the period of adjuvant tamoxifen treatment is an independent poor prognostic factor in patients with early breast cancer. No significant financial relationships to disclose.
SET Domain–Containing Protein 4 Epigenetically Controls Breast Cancer Stem Cell Quiescence
Authors: Sen Ye, Yan-Fu Ding, Wen-Huan Jia, Xiao-Li Liu, Jing-Yi Feng, Qian Zhu, Sun-Li Cai, Yao-Shun Yang, Qian-Yun Lu, Xue-Ting Huang, Jin-Shu Yang, Sheng-Nan Jia, Guo-Ping Ding, Yue-Hong Wang, Jiao-Jiao Zhou, Yi-Ding Chen, Wei-Jun Yang
Journal: Cancer Research (2019)

Abstract Quiescent cancer stem cells (CSC) play important roles in tumorigenesis, relapse, and resistance to chemoradiotherapy. However, the determinants of CSC quiescence and how they sustain themselves to generate tumors and relapse beyond resistance to chemoradiotherapy remains unclear. Here, we found that SET domain–containing protein 4 (SETD4) epigenetically controls breast CSC (BCSC) quiescence by facilitating heterochromatin formation via H4K20me3 catalysis. H4K20me3 localized to the promoter regions and regulated the expression of a set of genes in quiescent BCSCs (qBCSC). SETD4-defined qBCSCs were resistant to chemoradiotherapy and promoted tumor relapse in a mouse model. Upon activation, a SETD4-defined qBCSC sustained itself in a quiescent state by asymmetric division and concurrently produced an active daughter cell that proliferated to produce a cancer cell population. Single-cell sequence analysis indicated that SETD4+ qBCSCs clustered together as a distinct cell type within the heterogeneous BCSC population. SETD4-defined quiescent CSCs were present in multiple cancer types including gastric, cervical, ovarian, liver, and lung cancers and were resistant to chemotherapy. SETD4-defined qBCSCs had a high tumorigenesis potential and correlated with malignancy and chemotherapy resistance in clinical breast cancer patients. Taken together, the results from our previous study and current study on six cancer types reveal an evolutionarily conserved mechanism of cellular quiescence epigenetically controlled by SETD4. Our findings provide insights into the mechanism of tumorigenesis and relapse promoted by SETD4-defined quiescent CSCs and have broad implications for clinical therapies. Significance: These findings advance our knowledge on the epigenetic determinants of quiescence in cancer stem cell populations and pave the way for future pharmacologic developments aimed at targeting drug-resistant quiescent stem cells.
Costs of case-finding uncovered: time to revisit COPD’s value pyramid?
Authors: Job F M van Boven
Journal: Thorax (2019)

To screen or to target the missing millions with chronic obstructive pulmonary disease (COPD)? Moreover, what if we decide to invest in case-finding: do we get value for our money? Now, that’s the real question! First, however, we should establish what to pay for. Earlier research showed that one-third to half of COPD patients have not been diagnosed.1 2 Indeed, even if patients are already on the radar of a general practitioner (GP), opportunities to diagnose COPD are frequently being missed.3 COPD is still a major cause of severe patient symptoms (eg, breathlessness), costly hospital admissions and death.4 5 Notably, it is likely that earlier diagnosis and treatment to lessen breathlessness could reduce the risk of comorbidities associated with low physical activity developing and so contribute to healthier ageing.5 Those in favour of case-finding have, therefore, recently highlighted the need for early detection.6 Sceptics, on the other hand, argue that it is only useful if we can effectively slow down or halt the natural course of the disease.7 

Over the last decade, multiple COPD case-finding strategies have been described.8 9 Most strategies seem effective, but generally few large, well-designed randomised controlled trials (RCTs) have been performed and outcomes have been very heterogeneous.10 Notably, this heterogeneity has limited our evidence on the optimal population at-risk to target, the best screening tools and diagnostic tests to use and, moreover, the cost-effectiveness of active case-finding. Limited evidence has also resulted in guideline committees and policymakers being hesitant in widely promoting case-finding.

This brings us back to the first question: what do the current guidelines actually tell us? The updated Global Initiative for Chronic Obstructive Lung Disease (GOLD) report discourages spirometry in asymptomatic populations without exposure to tobacco or other noxious stimuli. However, since 2019, it …
Response by Fearon et al to Letter Regarding Article, “Accuracy of Fractional Flow Reserve Derived From Coronary Angiography”
Authors: William F. Fearon, Ran Kornowski, Bernard De Bruyne
Journal: Circulation (2019)

We thank Westra and colleagues for their interest in the FAST-FFR (Fractional Flow Reserve Derived From Routine Coronary Angiography [FFR angio ] Accuracy Versus Standard Fractional Flow Reserve [FFR]) study. 1 On their concern about the disqualification of 4.2% of FFR angio tracings by the core laboratory run by CathWorks, the sponsor of the FAST-FFR trial, we remind the reader that the FFR angio tracings were evaluated by the core laboratory in a blinded fashion to the FFR results, which were sent directly from the enrolling site to an independent core laboratory, and that the FFR angio tracings were excluded based on strict prespecified criteria and communicated to the investigators at the enrolling site.Other groups investigating alternative methods for deriving FFR from the coronary angiogram also excluded cases (up to 9%) based on core laboratory review, and it is unclear if their results represent the site-reported or core laboratory-reported values. 2,3 In the FAST-FFR trial, when on-site FFR angio results (without any excluded cases) were compared with FFR, the sensitivity was 89.7% (95% CI, 84.8-94.7)and the specificity was 89.8% (95% CI, 85. 5-94.2),both well above the prespecified performance goals.About quantifying the total time required to complete the FFR angio analysis, this was not within the scope of the trial.Of note, the acquisition of additional angiographic images after attempting FFR angio analysis was prohibited.We agree that further comparisons of the time requirements for FFR angio with FFR will provide important data and will be the goal of future studies.
Fully Automated, Quality-Controlled Cardiac Analysis From CMR
Authors: Bram Ruijsink, Esther Puyol-Antón, Ilkay Oksuz, Matthew Sinclair, Wenjia Bai, Julia A. Schnabel, Reza Razavi, Andrew P. King
Journal: JACC. Cardiovascular imaging (2019)

This study sought to develop a fully automated framework for cardiac function analysis from cardiac magnetic resonance (CMR), including comprehensive quality control (QC) algorithms to detect erroneous output.Analysis of cine CMR imaging using deep learning (DL) algorithms could automate ventricular function assessment. However, variable image quality, variability in phenotypes of disease, and unavoidable weaknesses in training of DL algorithms currently prevent their use in clinical practice.The framework consists of a pre-analysis DL image QC, followed by a DL algorithm for biventricular segmentation in long-axis and short-axis views, myocardial feature-tracking (FT), and a post-analysis QC to detect erroneous results. The study validated the framework in healthy subjects and cardiac patients by comparison against manual analysis (n = 100) and evaluation of the QC steps' ability to detect erroneous results (n = 700). Next, this method was used to obtain reference values for cardiac function metrics from the UK Biobank.Automated analysis correlated highly with manual analysis for left and right ventricular volumes (all r > 0.95), strain (circumferential r = 0.89, longitudinal r > 0.89), and filling and ejection rates (all r ≥ 0.93). There was no significant bias for cardiac volumes and filling and ejection rates, except for right ventricular end-systolic volume (bias +1.80 ml; p = 0.01). The bias for FT strain was <1.3%. The sensitivity of detection of erroneous output was 95% for volume-derived parameters and 93% for FT strain. Finally, reference values were automatically derived from 2,029 CMR exams in healthy subjects.The study demonstrates a DL-based framework for automated, quality-controlled characterization of cardiac function from cine CMR, without the need for direct clinician oversight.
Regulatory T cells mediate resistance to radiotherapy in head and neck squamous cell carcinoma.
Authors: Ayman Oweida, Laurel Darragh, Shilpa Bhatia, David Raben, Lynn Heasley, Raphael Nemenoff, Eric Clambey, Sana Karam
Journal: Journal of Clinical Oncology (2019)

70 Background: Head and neck tumors are highly enriched in regulatory T cells which dampen the response to radiotherapy by creating an immune-inhibitory microenvironment. We explored mechanisms of Treg infiltration and assessed their modulation by RT in murine models of HNSCC. Methods: Mechanisms of Treg infiltration were investigated in murine HNSCC tumors using whole genome sequencing and flow cytometry. Mice were treated with anti-CTLA-4, anti-CD-25 and/or anti-PD-L1 alone and in combination with RT. Tumor growth and survival were assessed. Flow cytometry was used to assess phenotypic and functional changes in intratumoral T cell populations. Multiplex ELISA was performed for assessment of cytokines. RNA Sequencing was performed to interrogate mechanisms of response and resistance to treatment. Results: Treatment with anti-CD-25 concurrently with RT led to significant tumor growth delay, enhanced T cell cytotoxicity, decreased Tregs and improved survival. In contrast CTLA-4 blockade did not affect tumor growth or survival. Treg depletion induced an influx of CD8 and CD4 T cells when combined with RT. In addition, Treg depletion in combination with RT transformed myeloid populations decreasing M2 macrophages and MDSCs and increasing M1 macrophages. Mechanistically, tumors secrete CCL20, a potent Treg chemoattractant responsible for creating a highly immunuosuppressive tumor microenvironment and potentially responsible for treatment resistance. Conclusions: These data reveal a critical role for regulatory T cells in mediating resistance to RT. Targeted depletion of Tregs represents an important mechanism of sensitizing tumors to RT. Our data support the design of clinical trials integrating targeted Treg inhibitors in the standard of care for cancer patients receiving RT.
Control of Synaptic Specificity by Establishing a Relative Preference for Synaptic Partners
Authors: Chundi Xu, Emma Theisen, Ryan Maloney, Jing Peng, Ivan Santiago, Clarence Yapp, Zachary Werkhoven, Elijah Rumbaut, Bryan Shum, Dorota Tarnogorska, Jolanta Borycz, Liming Tan, Maximilien Courgeon, Tessa Griffin, Raina Levin, Ian A. Meinertzhagen, Benjamin de Bivort, Jan Drugowitsch, Matthew Y. Pecot
Journal: Neuron (2019)
High C-reactive protein (CRP) level and leukocytosis as a prognostic factor for metastatic pancreatic cancer (MPC) patients with good performance status.
Authors: Masato Ozaka, Hiroshi Ishii, Seigo Yukisawa
Journal: Journal of Clinical Oncology (2012)

e14677 Background: Prognostic factor for metastatic pancreatic cancer patients (pts) with good performance status has not been fully evaluated. The objective is to investigate the prognostic factor for metastatic pancreatic cancer patients with good performance status. Methods: Data was collected from the medical records of patients at our hospital. The selection criteria were as follows: 1) histologically proven MPC, 2) ECOG performance status 0 or 1, 3) inoperable or recurrent metastatic disease treated with systemic chemotherapy between Sep. 2007 and June 2011. Results: There were 123 pts who met selection criteria in this study. The median age was 65 years (range, 41-86); male/female, 70/53 pts; the metastatic site was liver/peritoneum/lung/lymph nodes/others in 75/31/15/10/ pts. Median overall survival was 9.5 months, respectively. Of the 123, 11 pts showed leukocytosis (WBC&gt;10000) and 19 pts showed High CRP level (CRP&gt;2.0). Pts with leukocytosis and high CRP level showed significantly poor overall survival (4.44 and 4.44 months). A multivariate analysis demonstrated that a leukocytosis and high CRP level were independent unfavorable prognostic factors. Conclusions: High CRP level and leukocytosis may be a poor prognostic factor for MPC patients with good performance status.
Abstract 14117: Method of Assessing Medication Persistence and Clinical Outcomes: A Comparison of Patient Report and Pharmacy Fill Data From the ARTEMIS Trial
Authors: Alexander C Fanaroff, Eric D Peterson, Lisa A Kaltenbach, Gregg C Fonarow, Niteesh K Choudhry, Kevin J Anstrom, Timothy D Henry, David J Cohen, Eileen Fonseca, Naeem D Khan, Christopher P Cannon, Tracy Y Wang
Journal: Circulation (2018)

Background: While assessing medication persistence is important, the agreement and accuracy of patient report versus pharmacy fill records remain uncertain. Methods: In ARTEMIS, a randomized trial ...