tbuckley/cabot-search huggingface dataset:
Precision-Panc Master Protocol: Personalizing treatment for pancreatic cancer ISRCTN14879538—Part of Precision-Panc United Kingdom.
Authors: Juan W. Valle, T.R. Jeffry Evans, Colin J McKay, Judith Dixon-Hughes, James Paul, Jamie Stobo, Susie Cooke, Christine Willshire, Nicola Williams, Fraser Duthie, Andrew Biankin, David Kuang-Fu Chang
Journal: Journal of Clinical Oncology (2019)

TPS460 Background: A major challenge of lower incidence cancer types is that to make significant advances a network approach is required to coordinate research, generate greater clinical capacity and recruit sufficient patients. This is particularly the case for pancreatic cancer (PC). To address this, we established Precision-Panc, a synergistic and dynamic platform aligning “discovery”, “preclinical” and “clinical” therapeutic development. Methods: Central to the clinical development is the Precision-Panc Master Protocol, a multi-centre “portal” protocol recruiting patients with known or suspected PC, to enable enrolment into PRIMUS (Pancreatic canceR Individualised Multi-arm Umbrella Study), examining different treatment regimens and/or biomarker development. Eligible patients are identified prior to the diagnostic biopsy to obtain Stage 1 (Screening) Consent for extra tissue to be taken in the same biopsy setting. Patients who already have a diagnosis are asked to provide additional research biopsy. Once the PC diagnosis is made, Stage 2 (Registration) Consent is obtained for molecular profiling at the central reference laboratory using Precision-Panc NGS Diagnostic (bespoke clinical grade assay), including germline testing of 12 PC predisposition genes. The results may inform eligibility for a PRIMUS study. There is no sample size calculation due to the nature of the Master Protocol; however, individual PRIMUS studies will be appropriately powered according to their study design and primary endpoint. Results: Adults (aged &gt;16 years) with either a hypodense pancreatic mass highly suspicious of PC (+/- distant metastases) or histologically/cytologically confirmed PC and its variants; willing and able to undergo tumour biopsy to obtain sufficient tissue for molecular profiling; deemed suitable to receive chemotherapy and/or radiotherapy and/or surgery pending stage of disease; must give both Stage 1 and 2 informed consent. Conclusions: The study opened on 28 Dec 2017; by 25 Sep 2018, 67 patients have been screened for Precision-Panc, 43 of whom have gone on to be registered and 19 have then been randomised to the PRIMUS-001 study (first-line metastatic). Clinical trial information: ISRCTN14879538.
ESAM on the Cells of Endothelial Lineage Plays an Important Role in the Development of Definitive Hematopoiesis
Authors: Tomoaki Ueda, Takafumi Yokota, Yoshihiro Uno, Tomoji Mashimo, Takao Sudo, Tomohiko Ishibashi, Yukiko Doi, Yasuhiro Shingai, Akira Tanimura, Michiko Ichii, Sachiko Ezoe, Hirohiko Shibayama, Kenji Oritani, Yuzuru Kanakura
Journal: Blood (2018)
How Do We Reconcile Echocardiography, Computed Tomography, and Hybrid Imaging in Assessing Discordant Grading of Aortic Stenosis Severity?
Authors: Victoria Delgado, Marie-Annick Clavel, Rebecca T. Hahn, Linda Gillam, Jeroen Bax, Partho P. Sengupta, Philippe Pibarot
Journal: JACC. Cardiovascular imaging (2019)
Clara Cell 10-kd Protein (CC10) Modulates Superoxide Generation and Arachidonic Acid Metabolism via Formyl Peptide Receptor-Like 1 (FPRL1)
Authors: Li-Chen Chen, Jing Long Huang, Shau-Ku Huang, Ming-Ling Kuo, Ai-Hsuan Wu
Journal: Journal of Allergy and Clinical Immunology (2019)
Coca-Cola and obesity: study shows efforts to influence US Centers for Disease Control
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Correspondence between the Coca-Cola Company and the US Centers for Disease Control and Prevention (CDC) has revealed Coke’s efforts to influence the agency’s approach to tackling obesity, a new study has found.

Published in the Milbank Quarterly ,1 the paper said that emails reveal Coke’s interest in “gaining access to CDC employees, to lobby policymakers, and to frame the obesity debate by shifting attention and blame away from sugar-sweetened beverages.”

The emails also demonstrate Coke’s efforts to “advance corporate objectives, rather than health, including to influence the World Health Organization,” says the study.

The paper follows an investigation published by The BMJ last month,2 which showed how Coke had shaped obesity science and steered public health policy towards its own interests in China.

The latest study was based on emails …
Anticytokine Agents
Authors: Paul M Ridker
Journal: Circulation Research (2019)

The recognition that atherosclerosis is a complex chronic inflammatory disorder mediated through both adaptive and innate immunity has led to the hypothesis that anticytokine therapies targeting specific IL (interleukin) signaling pathways could serve as powerful adjuncts to lipid lowering in the prevention and treatment of cardiovascular disease. Cytokines involved in human atherosclerosis can be broadly classified as proinflammatory and proatherogenic (such as IL-1, IL-6, and TNF [tumor necrosis factor]) or as anti-inflammatory and antiatherogenic (such as IL-10 and IL-1rA). The recent CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) has shown that specific targeting of IL-1β can significantly reduce cardiovascular event rates without lipid or blood pressure lowering. In CANTOS, the magnitude of benefit of this cytokine-targeted approach to atherosclerosis treatment was associated to the magnitude of reduction of the central signaling cytokine IL-6 and the downstream clinical biomarker high-sensitivity CRP (C-reactive protein). By contrast, in the recent CIRT (Cardiovascular Inflammation Reduction Trial), low-dose methotrexate neither reduced IL-1β, IL-6, or high-sensitivity CRP nor lowered cardiovascular event rates. Taken together, these 2 contemporary trials provide proof of principle that focused cytokine inhibition, not broad-spectrum anti-inflammatory therapy, is likely to be crucial for atheroprotection. This review provides an overview of cytokines in atherosclerosis, the potential benefits and risks associated with targeted anticytokine therapies, and a look to the future of clinical practices addressing residual inflammatory risk.
Long-term outcome of laparoscopic versus open total gastrectomy for advanced gastric cancer: A propensity score-matched analysis.
Authors: Hayemin Lee, Junhyun Lee
Journal: Journal of Clinical Oncology (2019)

77 Background: Laparoscopic total gastrectomy (LTG) for advanced gastric cancer (AGC) is technically and oncologically challenging procedure for surgeons. The aim of this study is to compare technical safety and long-term oncologic feasibility of LTG for AGC patients compared to open total gastrectomy (OTG) using propensity score (PS)-matched analysis. Methods: Between 2004 and 2014, 185 patients (OTG: 127, LTG: 58) underwent total gastrectomy due to advanced gastric cancer. PS-matching was done using patients’ age, sex, American Society of Anesthesiologist (ASA) physical status, extent of lymph node dissection, presence of combined resection and pathological stage of gastric cancer. Comparisons were made based on surgical outcomes and long-term survival rates. Results: After PS-matching, 102 patients, respectively 51 patients for each group, were enrolled. LTG had longer tumor-free proximal resection margin (OTG 2.5 cm vs. LTG 3.0 cm, p = 0.008). Total number of retrieved lymph node and metastasized lymph node was similar in both groups. The retrieved number of lymph nodes around splenic hilum (#10 and #11d) was similar in both groups (p = 0.105). Longer operation time was required in LTG (OTG 240 min. vs. LTG 320 min, p = 0.002) but less intraoperative bleeding was observed in LTG (OTG 390 cc vs. LTG 276 cc, p &lt; 0.001). Patients of LTG were discharged earlier than OTG (OTG 12 days vs. LTG 10 days, p = 0.043). Overall morbidity and mortality of both group was similar. Between two groups, there was not a difference in 5-year overall survival rate (OTG 56.3% vs. LTG 56.5%, p = 0.597) or disease free survival rate (OTG 59.0% vs. LTG 67.6%, p = 0.455). Conclusions: For treating proximal AGC, LTG may be a technically and oncologically safe and feasible method.
Targeting Both BET and Crebbp/EP300 Proteins with the Novel Dual Inhibitor NEO2734 Leads to More Preclinical Anti-Tumor Activity in Diffuse Large B Cell Lymphomathan with Single BET or Crebbp/EP300 Inhibitors
Authors: Filippo Spriano, Eugenio Gaudio, Chiara Tarantelli, Gaetanina Golino, Luciano Cascione, Emanuele Zucca, Anastasios Stathis, Francis J. Giles, Francesco Bertoni
Journal: Blood (2018)
Precision Medicine for Sickle Cell Disease through Whole Genome Sequencing
Authors: Evadnie Rampersaud, Lance E. Palmer, Jane S. Hankins, Vivien A Sheehan, Wenjian Bi, Heather Mulder, Guolian Kang, Jeremie H. Estepp, Shuoguo Wang, Andrew Thrasher, Martha Villavicencio, Jason R Hodges, Wenan Chen, Ti-Cheng Chang, Yong Cheng, Michael Rusch, Yadav Sapkota, Akshay Sharma, Pavel Sumazin, Xing Tang, Amanda M. Brandow, Shawn Levy, Nidal Boulos, Celeste Rosencrance, Donald Yergeau, Jeffrey Lebensburger, Winfred Wang, Yutaka Yasui, John Easton, Michael R. DeBaun, James R. Downing, Jinghui Zhang, Gang Wu, Mitchell J. Weiss
Journal: Blood (2018)
Mechanical activation of noncoding-RNA-mediated regulation of disease-associated phenotypes in human cardiomyocytes
Authors: Aditya Kumar, Stephanie K. Thomas, Kirsten C. Wong, Valentina Lo Sardo, Daniel S. Cheah, Yang-Hsun Hou, Jesse K. Placone, Kevin P. Tenerelli, William C. Ferguson, Ali Torkamani, Eric J. Topol, Kristin K. Baldwin, Adam J. Engler
Journal: Nature Biomedical Engineering (2019)
Biofilm Propensity of Staphylococcus aureus Skin Isolates is Associated with Increased Severity and Barrier Dysfunction in the Mechanisms of the Progression of Atopic Dermatitis to Asthma in Children (MPAACH) Cohort
Authors: Tammy Gonzalez, Mariana L. Stevens, Asel Baatyrbek kyzy, Rosario Alarcon, Hua He, John Kroner, Daniel Spagna, Elaine Sidler, Lisa J. Martin, Jocelyn M. Biagini Myers, Gurjit K. Khurana Hershey, Andrew Herr
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 16976: Putting the Diabetes Prevention Program into Practice: 10 Years of Outcomes
Authors: Vidthya C Abraham, Patrick E McBride
Journal: Circulation (2017)

Introduction: The Diabetes Prevention Program (DPP) was a landmark trial that demonstrated an intensive lifestyle modification program targeting moderate weight loss decreases the progression of prediabetes to type 2 diabetes mellitus (DM) by 58%. Global efforts to translate this study into the community are ongoing due to a rising incidence and prevalence of prediabetes and diabetes. The Active Living and Learning Program (ALL) utilizes existing cardiac rehabilitation infrastructure at the University of Wisconsin to provide a community based lifestyle modification intervention based on the DPP. This study provides outcomes of the ALL over the past 10 years. Methods: Participants with prediabetes or newly diagnosed DM completed an 11-month group program, meeting once weekly for 12 weeks, then monthly for the remaining 8 months. Meetings were led by a registered dietician and an exercise physiologist, and included both group exercise sessions and an educational curriculum covering topics in behavioral chan...
Preventability of SCARs
Authors: G. Chaby, L. Valeyrie‐Allanore, T.A. Duong, B. Lebrun‐Vignes, B. Milpied, B. Sassolas, F. Tetart, P. Wolkenstein, O. Chosidow, L. Fardet
Journal: British Journal of Dermatology (2018)
Hemocyanin Is A Shrimp Allergen In The U.S.: Clinical And Immunological Profiles Of Food Challenge-Proven Shrimp Allergic Patients
Authors: Karen Thursday S. Tuano, Sara Anvari, Joud Hajjar, Filiz O. Seeborg, Lenora Mendoza Noroski, Jordan Scott Orange, Carla M. Davis
Journal: Journal of Allergy and Clinical Immunology (2019)
Quinidine-Responsive Polymorphic Ventricular Tachycardia in Patients With Coronary Heart Disease
Authors: Sami Viskin, Ehud Chorin, Dana Viskin, Aviram Hochstadt, Amir Halkin, Oholi Tovia-Brodie, John K. Lee, Elad Asher, Avishag Laish-Farkash, Guy Amit, Ofer Havakuk, Bernard Belhassen, Raphael Rosso
Journal: Circulation (2019)

Background: Polymorphic ventricular tachycardia (VT) without QT prolongation is well described in patients without structural heart disease (mainly idiopathic ventricular fibrillation and Brugada syndrome) and in patients with acute ST-elevation myocardial infarction. Methods: Retrospective study of patients with polymorphic VT related to coronary artery disease, but without evidence of acute myocardial ischemia. Results: The authors identified 43 patients in whom polymorphic VT developed within days of an otherwise uncomplicated myocardial infarction or coronary revascularization procedure. The polymorphic VT events were invariably triggered by extrasystoles with short (364±36 ms) coupling interval. Arrhythmic storms (4–16 events of polymorphic VT deteriorating to ventricular fibrillation) occurred in 23 (53%) patients. These arrhythmic storms were always refractory to conventional antiarrhythmic therapy, including intravenous amiodarone, but invariably responded to quinidine therapy. In-hospital mortality was 17% for patients with arrhythmic storm. Patients treated with quinidine invariably survived to hospital discharge. During long-term follow-up (of 5.6±6 years; range, 1 month to 18 years), 3 (16%) of patients discharged without quinidine developed recurrent polymorphic VT. There were no recurrent arrhythmias during quinidine therapy Conclusions: Arrhythmic storm with recurrent polymorphic VT in patients with coronary disease responds to quinidine therapy when other antiarrhythmic drugs (including intravenous amiodarone) fail.
Abstract 19447: Correlation of Early Echocardiographic Right Ventricular Dimension and MRI Right Ventricular Volumes Late After Tetralogy of Fallot Repair
Authors: Sara Hussain, Osman Al-Radi, Prisca Pondorfer, Lars Grosse-Wortmann, Luc Mertens, Glen Van Arsdell
Journal: Circulation (2015)

Introduction: Right Ventricular End-Diastolic Volume indexed (RVEDVi) obtained by MRI is an accurate measure of RV size and a marker for secondary complications. Echo RV measurements are used early in life after TOF repair for practical reasons. We sought to examine the correlation between early echo Right Ventricular End-Diastolic Dimension z-score (RVEDDz) and MRI RVEDVi at 15 years post-repair. The relationship between these parameters and repair technique is investigated. Methods: 185 TOF patients were repaired at our institution from 1996-2002. Repair techniques were: annulus preservation (AP=124), trans-annular patch (TAP=56), and Pulmonary valve replacement (n=5, patients excluded). Data was reviewed for outcomes, echo studies, and MRI reports. A linear ordinary least square model demonstrated the relationship between early RVEDDz and late RVEDVi (n=57) . Longitudinal analysis with mixed effects model was performed on 783 serial echocardiograms (n=146) to demonstrate the effect of technique on RVEDDz progression. Results: RVEDDz at 1-5 years post-repair was a significant predicator for late RVEDVi (p=0.0016). A change in RVEDDz from 0-3 predicted an increase in RVEDVi of 28 mL. TAP repair was an independent predictor of a larger RVEDVi (p=0.0011). TAP was associated with more RV dilation throughout follow-up (0.37 RVEDDz higher every 5 years, p&lt;0.0001). TAP patients had larger late RV volumes for the same early RVEDDz as those with AP repair (Fig. 1). The same findings were demonstrated in a sub-analysis of anatomically matched patients who could have had either TAP or AP based on surgeon choice. Conclusion: These results from a single institution support the use of RVEDDz by echo as an early maker for late MRI RV volumes in TOF. Early identification of high risk patients may influence decisions around follow-up and re-interventions. Larger population studies are needed to confirm these findings and the effects of technique on long-term RV health. Fig 1.
A PET Glutamate Analogue to Measure Cancer Cell Redox State and Oxidative Stress: Promise and Paradox
Authors: Hsiaoju S. Lee, Austin R. Pantel, Rong Zhou, David A. Mankoff
Journal: Cancer Research (2019)

Abstract [18F]FSPG was shown to provide an indirect measure of the cellular redox state and may be used as an early indicator of therapy response to cancer therapies that cause oxidative stress. A somewhat paradoxical finding was that reduced [18F]FSPG cellular uptake was associated with either lower cellular concentrations of cystine or glutamate, despite opposing the transport of these substances in the Xc− antiporter, for which [18F]FSPG is also a substrate. Further studies of the kinetics of [18F]FSPG will help elucidate the factors mediating a decline in [18F]FSPG with oxidative stress. See related article by McCormick et al, p. 853
TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer
Authors: Roisin M. Connolly, Jeffrey P. Leal, Lilja Solnes, Chiung-Yu Huang, Ashley Carpenter, Katy Gaffney, Vandana Abramson, Lisa A. Carey, Minetta C. Liu, Mothaffar Rimawi, Jennifer Specht, Anna Maria Storniolo, Vicente Valero, Christos Vaklavas, Ian E. Krop, Eric P. Winer, Melissa Camp, Robert S. Miller, Antonio C. Wolff, Ashley Cimino-Mathews, Ben H. Park, Richard L. Wahl, Vered Stearns
Journal: Journal of Clinical Oncology (2019)

Predictive biomarkers to identify patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who may benefit from targeted therapy alone are required. We hypothesized that early measurements of tumor maximum standardized uptake values corrected for lean body mass (SULmax) on [18F]fluorodeoxyglucose positron emission tomography/computed tomography would predict pathologic complete response (pCR) to neoadjuvant pertuzumab and trastuzumab (PT).Patients with stage II/III, estrogen receptor-negative, HER2-positive breast cancer received four cycles of neoadjuvant PT. [18F]Fluorodeoxyglucose positron emission tomography/computed tomography was performed at baseline and 15 days after PT initiation (C1D15). Eighty evaluable patients were required to test the null hypothesis that the area under the curve of percentage of change in SULmax by C1D15 predicting pCR is less than or equal to 0.65, with a one-sided type I error rate of 10%.Eighty-eight women were enrolled (83 evaluable), and 85% (75 of 88) completed all four cycles of PT. pCR after PT alone was 34%. Receiver operating characteristic analysis yielded an area under the curve of 0.76 (90% CI, 0.67 to 0.85), which rejected the null hypothesis. Between patients who obtained pCR versus not, a significant difference in median percent reduction in SULmax by C1D15 was observed (63.8% v 33.5%; P < .001), an SULmax reduction greater than or equal to 40% was more prevalent (86% v 46%; P < .001; negative predictive value, 88%; positive predictive value, 49%), and a significant difference in median C1D15 SULmax (1.6 v 3.9; P < .001) and higher proportion of C1D15 SULmax less than or equal to 3 (93% v 38%; P < .001; negative predictive value, 94%; positive predictive value, 55%) were observed.Early changes in SULmax predict response to four cycles of PT in estrogen receptor-negative, HER2-positive breast cancer. Once optimized, this quantitative imaging strategy may facilitate a more tailored approach to therapy in this setting.
The Influence of Adjuvant Systemic Regimens on Contralateral Breast Cancer Risk and Receptor Subtype
Authors: Iris Kramer, Michael Schaapveld, Hester S A Oldenburg, Gabe S Sonke, Danielle McCool, Flora E van Leeuwen, Koen K Van de Vijver, Nicola S Russell, Sabine C Linn, Sabine Siesling, C Willemien Menke-van der Houven van Oordt, Marjanka K Schmidt
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background An increasing number of breast cancer (BC) survivors are at risk of developing contralateral breast cancer (CBC). We aimed to investigate the influence of various adjuvant systemic regimens on, subtype-specific, risk of CBC. Methods This population-based cohort study included female patients diagnosed with first invasive BC between 2003 and 2010; follow-up was complete until 2016. Clinico-pathological data were obtained from the Netherlands Cancer Registry and additional data on receptor status through linkage with PALGA: the Dutch Pathology Registry. Cumulative incidences (death and distant metastases as competing risk) and hazard ratios (HRs) were estimated for all invasive metachronous CBC and CBC subtypes. Results Of 83 144 BC patients, 2816 developed a CBC; the 10-year cumulative incidence was 3.8% (95% confidence interval [CI] = 3.7% to 4.0%). Overall, adjuvant chemotherapy (HR = 0.70, 95% CI = 0.62 to 0.80), endocrine therapy (HR = 0.46, 95% CI = 0.41 to 0.52), and trastuzumab with chemotherapy (HR = 0.57, 95% CI = 0.45 to 0.73) were strongly associated with a reduced CBC risk. Specifically, taxane-containing chemotherapy (HR = 0.48, 95% CI = 0.36 to 0.62) and aromatase inhibitors (HR = 0.32, 95% CI = 0.23 to 0.44) were associated with a large CBC risk reduction. More detailed analyses showed that endocrine therapy statistically significantly decreased the risk of estrogen receptor (ER)-positive CBC (HR = 0.41, 95% CI = 0.36 to 0.47) but not ER-negative CBC (HR = 1.32, 95% CI = 0.90 to 1.93) compared with no endocrine therapy. Patients receiving chemotherapy for ER-negative first BC had a higher risk of ER-negative CBC from 5 years of follow-up (HR = 2.84, 95% CI = 1.62 to 4.99) compared with patients not receiving chemotherapy for ER-negative first BC. Conclusion Endocrine therapy, chemotherapy, as well as trastuzumab with chemotherapy reduce CBC risk. However, each adjuvant therapy regimen had a different impact on the CBC subtype distribution. Taxane-containing chemotherapy and aromatase inhibitors were associated with the largest CBC risk reduction.