tbuckley/cabot-search huggingface dataset:
Mismatch repair/microsatellite instability (MMR/MSI) testing practices among United States physicians treating patients (pts) with advanced/metastatic colorectal cancer (mCRC).
Authors: Jennifer Eriksson, Mayur Amonkar, Gemma Thomson, Jeremy Lambert, Mia Malmenas, Monica Chase, Lucy Sun, Linda Grossman Kollmar, Michelle Vichnin
Journal: Journal of Clinical Oncology (2019)

533 Background: Approximately 12-15% of all CRCs are associated with defects in the DNA MMR pathway. NCCN 2017 guidelines endorsed universal MMR/MSI testing for all pts with a personal history of CRC. The study objective was to assess US physicians’ MMR/MSI genetic testing practices for mCRC pts. Methods: A non-interventional, cross-sectional online survey was conducted among 151 physicians (91 oncologists, 15 surgeons and 45 pathologists) treating mCRC pts in the US. A draft survey was first developed based on a targeted literature review and exploratory interviews with 15 physicians, and then pilot tested with a new series of 10 physicians. Physicians were eligible if they were US based with at least 5 years of experience treating CRC pts, had at least one mCRC pt in their routine care in the past 6 months of practice, and experienced with MMR/MSI testing including having ordered at least 1 MMR/MSI test for CRC in the past 6 months. Physicians were invited to participate through a market research panel. Descriptive and logistic regression analyses were performed. Results: Awareness of specific MMR/MSI testing guidelines was high (N = 127, 84.1%). Of those, 93.7% (119/127) physicians had awareness of specific published guidelines with majority 67.2% (80/119) being aware of NCCN guidelines. Universal testing for all CRC pts was performed by 68.9% (104/151) physicians, while 29.8% (45/151) selectively orders the test for some CRC pts. Key barriers for testing included insufficient tissue sample to enable running the test (48.3%, 73/151), patient refusal to have the test done (35.8%, 54/151) and insurance cost concerns for the pts (31.1%, 47/151), while 27.2% (41/151) reported no barriers. There were no statistically significant differences based on physician specialty, practice type and years of practice. Conclusions: The survey demonstrated high awareness and compliance with MMR/MSI testing guidelines although universal testing rates seem to be suboptimal. Addressing the key physician barriers to testing along with increased communication and education on the benefits of testing may help to enhance testing rates.
Surgical Resection of SCLC: Prognostic Factors and the Tumor Microenvironment
Authors: Xiaoliang Zhao, Bhaskar Kallakury, Joeffrey J. Chahine, Dan Hartmann, YuWen Zhang, Yulong Chen, Hua Zhang, Bin Zhang, Changli Wang, Giuseppe Giaccone
Journal: Journal of Thoracic Oncology (2019)
Left Ventricular Spherical Index Is an Independent Predictor for Clinical Outcomes in Patients With Nonischemic Dilated Cardiomyopathy
Authors: Yaodan Liang, Weihao Li, Rui Zeng, Jiayu Sun, Ke Wan, Yuanwei Xu, Yu Cao, Qing Zhang, Yuchi Han, Yucheng Chen
Journal: JACC. Cardiovascular imaging (2019)
A retrospective analysis of third-line treatment in advanced gastric cancer.
Authors: Yasunobu Ishizuka, Tetsuji Terazawa, Hiroki Yukami, Toshifumi Yamaguchi, Shin Kuwakado, Takayuki Kii, Masahiro Goto, Kazuhide Higuchi
Journal: Journal of Clinical Oncology (2019)

83 Background: As a result of ATTRACTION2, nivolumab was added to the third line treatment in advanced gastric cancer (AGC), but the response rate was about 10%. As there is no predictive biomarker and no comparison with cytotoxic regimen, it is difficult to choice the regimen. Therefore, we examined the treatment outcome of cytotoxic regimen in third line treatment in the real world retrospectively. Methods: We retrospectively evaluated efficacy and safety of cytotoxic regimen as third-line treatment in patients with AGC between July 2015 and December 2017. Results: Among 138 patients received chemotherapy as first line, 29 patients (21%) received third line therapy. The characteristics were as follows; the median age, 70 years old (range 34-80); male/female, 19 (66%)/10 (34%); performance status (PS) 0/1/2, 7/18/4. The overall response rate was 19% and the disease control rate was 38%. The median overall survival (OS) was 6.6 months and the progression free survival was 3.8 months. The most common grade 3/4 hematological toxicities were neutropenia (27%), followed by anemia (27%) and febrile neutropenia (13.7%). Grade 3/4 nonhematological toxicities included anorexia (27.6%), diarrhea (10%), nausea (10%). Conclusions: Cytotoxic regimen as third line showed acceptable activity, but only 21% of patients could received the third line chemotherapy. The further investigation of predictive biomarker of nivolumab is expected.
Celecoxib With Neoadjuvant Chemotherapy for Breast Cancer Might Worsen Outcomes Differentially by COX-2 Expression and ER Status: Exploratory Analysis of the REMAGUS02 Trial
Authors: Anne-Sophie Hamy, Sandrine Tury, Xiaofei Wang, Junheng Gao, Jean-Yves Pierga, Sylvie Giacchetti, Etienne Brain, Barbara Pistilli, Michel Marty, Marc Espié, Gabriel Benchimol, Enora Laas, Marick Laé, Bernard Asselain, Brice Aouchiche, Martin Edelman, Fabien Reyal
Journal: Journal of Clinical Oncology (2019)

PURPOSE The overexpression of cyclooxygenase 2 (COX-2) gene, also known as prostaglandin-endoperoxide synthase 2 ( PTGS2), occurs in breast cancer, but whether it affects response to anticox drugs remains unclear. We investigated the relationships between PTGS2 expression, celecoxib use during neoadjuvant chemotherapy (NAC), and both event-free survival (EFS) and overall survival (OS). MATERIALS AND METHODS We analyzed a cohort of 156 patients with human epidermal growth factor receptor 2 –negative breast cancer from the REMAGUS02 (ISRCTN Registry No. 10059974) trial with pretreatment PTGS2 expression data. Patients were treated by sequential NAC (epirubicin plus cyclophosphamide followed by docetaxel with or without celecoxib). Experimental validation was performed on breast cancer cell lines. The Cancer and Leukemia Group B (CALGB) 30801 ( ClinicalTrials.gov identifier: NCT01041781) trial that tested chemotherapy with or without celecoxib in patients with lung cancer served as an independent validation cohort. RESULTS After 94.5 months of follow-up, EFS was significantly lower in the celecoxib group (hazard ratio [HR], 1.7; 95% CI, 1 to 2.88; P = .046). A significant interaction between PTGS2 expression and celecoxib use was detected ( P interaction = .01). In the PTGS2-low group (n = 100), EFS was lower in the celecoxib arm (HR, 3.01; 95% CI, 1.45 to 6.24; P = .002) than in the standard treatment arm. Celecoxib use was an independent predictor of poor EFS, distant relapse–free survival, and OS. Celecoxib in addition to docetaxel enhanced cell viability in PTGS2-low cell lines but not in PTGS2-high cell lines. In CALGB 30801, a trend toward poorer progression-free survival was observed in the patients with low urinary metabolite of prostaglandin E2 who received celecoxib (HR = 1.57; 95% CI, 0.87 to 2.84; P = .13). CONCLUSION Celecoxib use during chemotherapy adversely affected survival in patients with breast cancer, and the effect was more marked in PTGS2-low and/or estrogen receptor–negative tumors. COX-2 inhibitors should preferably be avoided during docetaxel use in patients with breast cancer who are undergoing NAC.
Esophageal Eosinophilia is Present in Some Peanut Allergic Patients
Authors: Nielsen Fernandez-Becker, Benjamin L. Wright, Neeraja Kambham, Kelly P. Shim, Natasha Purington, Andrew J. Long, Mindy Tsai, Scott Boyd, Stephen J. Galli, Kari C. Nadeau, R. Sharon Chinthrajah
Journal: Journal of Allergy and Clinical Immunology (2019)
Transfusion Practice Following Intracranial Hemorrhage in Acute Leukemia: An Institutional Review
Authors: Shannon Nixon, Dawn Maze, Eshetu G Atenafu, Danielle Brandys, Cindy Susan Murray, Suzanne Rowland, Mary Clementine Doherty, Amanda Wolfe, Benjamin YM Kwan, Eugene Yu, Breanne Lechner, Lani Lieberman
Journal: Blood (2018)
Incidence of Thrombocytopenia and Heparin Induced Thrombocytopenia in Patients Receiving Extracorporeal Membrane Oxygenation (ECMO) Compared to Cardiopulmonary Bypass and the Limited Sensitivity of Pre-Test Probability Score
Authors: Deepa Jayakody Arachchillage, Sanjay Khanna, Christophe Vandenbriele, Jonthan Dutton, Alex Rosenberg, TC Aw, Winston Banya, Maurizio Passariello, Michael Laffan, Stephane Ledot, Brijesh Patel
Journal: Blood (2018)
Abstract 17250: Clinical Outcomes of Catheter Ablation of Atrial Fibrillation in Patients With Left Ventricular Dysfunction When Compare to Pharmacological Rate Control
Authors: Yutao Xi, Xiaomeng Yin, Lianjun Gao, Dong Chang, Yanzong Yang, Yunlong Xia, Jie Cheng
Journal: Circulation (2016)

Background: Catheter ablation (CA) of atrial fibrillation (AF) in patients with heart failure (HF) is increasing in use, but long-term outcomes are controversial and sparse. This study compared the efficacy and safety of CA to medical treatment of AF in patients with HF. Methods: Three groups of HF patients who underwent AF treatment were enrolled: 120 patients with congestive HF who were referred for first CA (AFHF-CA); 150 patients with congestive HF who were underwent medical rate control (AFHF-Medical); and 150 patients with normal heart function (AF-CA) who have matched age, gender and classification of atrial fibrillation with AFHF-CA. Patients were followed for 30-month, primary outcomes of AF recurrence, hospitalization, heart failure, stroke, death, and cardiac function were measured. Results: Recruited patients’ average age was 61±8.7 years old, and 60% male. All classifications of AF were even distributed within the three treatment groups (p=0.57); with average AF duration of 80 ± 83 days (p=0....
Survival of Single Positive Thymocytes Depends upon Developmental Control of RIPK1 Kinase Signaling by the IKK Complex Independent of NF-κB
Authors: Louise V. Webb, Alessandro Barbarulo, Jelle Huysentruyt, Tom Vanden Berghe, Nozomi Takahashi, Steven Ley, Peter Vandenabeele, Benedict Seddon
Journal: Immunity (2019)

NF-κB (nuclear factor κB) signaling is considered critical for single positive (SP) thymocyte development because loss of upstream activators of NF-κB, such as the IKK complex, arrests their development. We found that the compound ablation of RelA, cRel, and p50, required for canonical NF-κB transcription, had no impact upon thymocyte development. While IKK-deficient thymocytes were acutely sensitive to tumor necrosis factor (TNF)-induced cell death, Rel-deficient cells remained resistant, calling into question the importance of NF-κB as the IKK target required for thymocyte survival. Instead, we found that IKK controlled thymocyte survival by repressing cell-death-inducing activity of the serine/threonine kinase RIPK1. We observed that RIPK1 expression was induced during development of SP thymocytes and that IKK was required to prevent RIPK1-kinase-dependent death of SPs in vivo. Finally, we showed that IKK was required to protect Rel-deficient thymocytes from RIPK1-dependent cell death, underscoring the NF-κB-independent function of IKK during thymic development.
Abstract A073: Metabolism of saturated fatty acids accelerates Src-mediated prostate tumor progression
Authors: SUNGJIN KIM, Xiangkun Yang, Qianjin Li, Meng Wu, Zanna Beharry, Michael Bartlett, Alicja Bielawska, Houjian Cai
Journal: Cancer Research (2018)

Abstract The association of dietary fatty acids (FAs) with the risk of aggressive prostate cancer is controversial. The mechanisms of supporting how dietary FAs promote cancer progression are largely unknown. The expression and/or activity of Src family kinases are frequently elevated in several cancers, including advanced prostate cancer. This study demonstrates that dietary FAs accelerated Src-mediated prostate tumorigenesis and prostate cancer cell growth in vivo. Additionally, high dietary fat compromised the ability of dasatinib to block the oncogenic signaling of Src kinase. Metabolism of exogenous FAs, in particular palmitic and myristic acids, increased biosynthesis of acyl-CoAs and altered ceramide levels, in particular C16:0 ceramide. The combination of these effects elevated levels of myristoylated Src, increased the amount of Src in detergent resistant membranes, and enhanced Src kinase mediated oncogenic signaling. Targeting myristoylation of Src kinase, which is required for its association at the cellular membrane, blocked high fat diet-accelerated tumorigenesis in vivo. These findings illustrate how the metabolism of saturated FAs can accelerate Src-driven prostate tumor progression and suggest that prostate cancer survivors may benefit from a diet low in saturated fat. Citation Format: SUNGJIN KIM, Xiangkun Yang, Qianjin Li, Meng Wu, Zanna Beharry, Michael Bartlett, Alicja Bielawska, Houjian Cai. Metabolism of saturated fatty acids accelerates Src-mediated prostate tumor progression [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A073.
When binary and continuous responses disagree
Authors: Fengchen Ouyang
Journal: Annals of the Rheumatic Diseases (2019)

Figure 1 Non-responders commonly, but variably, discontinue drug.The LUNDEX method multiplies the proportion of responders with proportion of adherers, at a fixed time point.It is an elegant solution to variable non-responder discontinuation when response is defined using adherers as the denominator, but not all patients.The latter is a common approach to define response in observational studies, but is not compatible with the LUNDEX.Readers should also note that patients who would have otherwise responded may discontinue for other reasons (eg, adverse events), which the LUNDEX does not account for.on July 17,
Reproductive health outcomes in women with psoriatic arthritis
Authors: Kieran Murray, Louise Moore, Fionnuala McAuliffe, Douglas J Veale
Journal: Annals of the Rheumatic Diseases (2019)

Reproductive health outcomes in women with psoriatic arthritisThere are now high-quality data showing rheumatoid arthritis improves in pregnancy and flares post partum, and that active disease in pregnancy may be associated with adverse fetal outcomes such as low birth weights.However, in psoriatic arthritis (PsA), the data are less clear.][3] Only one of those studies was prospective and many lack disease activity scores.Much of the data also predate the widespread use of biologic disease-modifying antirheumatic drugs (bDMARDs) in pregnancy and so may not reflect current clinical practice.A recent abstract reviewing a Swedish patient registry reported increased odds of preterm birth, induction of labour and caesarean section in PsA pregnancies compared with population comparators. 4onsecutive female patients with PsA planning pregnancy or were pregnant seen by our multidisciplinary rheumatology reproductive health service were managed using our evidence-based reproductive care pathway and followed prospectively.Age,
Selinexor in Combination with Cladribine, Cytarabine and G-CSF for Relapsed or Refractory AML
Authors: Geoffrey L. Uy, Michael P Rettig, Theresa Fletcher, Peter A Riedell, Keith E. Stockerl-Goldstein, Armin Ghobadi, Meagan Jacoby, Amanda F. Cashen, Rizwan Romee, Iskra Pusic, Camille N. Abboud, Mark A. Schroeder, Ravi Vij, Peter Westervelt, John F DiPersio
Journal: Blood (2017)
Correlation between MPN-SAF TSS and EORTC QLQ-C30 Scores in Patients with PV: Data from the Reveal Study
Authors: Ivy Altomare, Aaron T. Gerds, David Lessen, Philomena Colucci, Shreekant Parasuraman, Dilan Chamikara Paranagama, Ruben A. Mesa
Journal: Blood (2018)
Abstract IA05: Early steps in lung oncogenesis
Authors: Samuel M. Janes
Journal: Clinical Cancer Research (2018)

Abstract Lung cancer is the biggest cancer killer of men and women, and there has been no improvement in survival over the last 50 years. To reduce the mortality of lung cancer, we need to both detect and treat it earlier, ideally at a preinvasive cancer stage before progression into full-blown invasive cancer. This would allow us to initiate treatment in a timely manner, increasing the chances of cure and saving lives. Lung cancers arise from preinvasive lesions but, interestingly, not all these lesions progress to cancer. We believe that understanding the differences between the lesions that progress to invasive cancer and those that disappear will direct us to the key proteins and genes that are mis-expressed, or inappropriately switched on or off, that lead to invasive cancer formation. My talk will outline studies that shed new understanding on how lung cancer develops and identify novel biological markers that accurately predict whether a lesion will eventually grow into a cancer. This, I hope, will enable targeting potential therapies to those patients with lesions that are likely to progress and identify the key genes and proteins associated with cancer development, thereby opening the possibility of developing chemoprophylactic therapeutic approaches to prohibit cancer development. Citation Format: Samuel M. Janes. Early steps in lung oncogenesis [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA05.
18β-Glycyrrhetic Acid Modulates Th1/Th17/Th22/Regulatory T Cells Homeostasis Via HMGB1/NF-κB Signaling Pathway in Immune Thrombocytopenia
Authors: Haoyi Wang, Yajing Zhao, Ning An, Panpan Han, Sun Yunqi, Ming Hou
Journal: Blood (2018)
Abstract 18710: Injectable Hydrogels for Minimally Invasive Delivery to Limit Infarct Induced Left Ventricular Remodeling and Mitral Regurgitation
Authors: Christopher B Rodell, Madonna E Lee, Hua Wang, Kia N Zellars, Paige E Perreault, Joseph H Gorman, Jonathan F Wenk, Francis G Spinale, Robert C Gorman, Jason A Burdick
Journal: Circulation (2016)

Introduction and Hypothesis: Injectable hydrogels limit LV remodeling and progressive heart failure post-MI by bulking and stiffening the infarct to reduce wall stress. A material with therapeutic ...
Abstract 20330: Noninvasive Tissue Adhesive for Cardiac Implantable Electrical Device Pocket Closure: The TAPE Study
Authors: Scott M Koerber, Troy Loethen, Mohit Turagam, Frank Cuoco, Sandeep Gautam
Journal: Circulation (2017)

Introduction: Device infection is a known complication for cardiac implantable electrical devices (CIED). Ensuring complete pocket closure can be time consuming, but is vital to prevent infection. The Zip® Surgical Skin Closure (ZIP) is a noninvasive adhesive device applied to the skin as an alternative to sutures for the subcuticular layer. Hypothesis: We hypothesized using this device would decrease pocket closure times while not increasing pocket infections. Methods: Consecutive new implants, upgrades and generator changes from October 2015 to April 2017 were included. Subcutaneous devices were excluded. A total of 175 patients were included, ZIP (n=80) and Suture (n=95). Pocket closure time (subcutaneous suture to dressing application) and total procedure time (local anesthetic to dressing application) and were measured. Pocket infections were defined as infections leading to extraction or wound dehiscence requiring repeat procedure or explant. Statistical analysis was performed using, STATA 14, chi s...
Dupilumab Improves Lung Function and Reduces Severe Exacerbation Rate in Patients With Uncontrolled, Moderate-to-Severe Asthma With or Without Comorbid Allergic Rhinitis: Results From the Phase 3 LIBERTY ASTHMA QUEST Study
Authors: William W. Busse, Jorge F. Maspero, Nicola A. Hanania, J. Mark FitzGerald, Linda B. Ford, Megan Rice, Yufang Lu, Paul Rowe, Heribert Staudinger, Nikhil Amin, Marcella Ruddy, Neil M.H. Graham, Ariel Teper
Journal: Journal of Allergy and Clinical Immunology (2019)
Increased integrity of circulating cell-free DNA in patients suffering from nasopharyngeal carcinoma
Authors: Allen K. Chan, Jun Zhang, Sing Fai Leung, Anthony T. Chan, Dennis Y. Lo
Journal: Cancer Research (2004)

4267  The existence of circulating cell-free DNA was first described more than 50 years ago. A number of groups have shown that circulating cell-free DNA in cancer patients exhibits certain neoplastic characteristics, thus opening up new possibilities of using plasma nucleic acids for the diagnosis and monitoring of cancers. In this study, we investigated the concentrations of plasma DNA, as well as the integrity of these DNA species, in patients suffering from nasopharyngeal carcinoma. Thirty-one patients with newly diagnosed nasopharyngeal carcinoma and thirty healthy control subjects were recruited for the study. In the first part, plasma DNA concentrations of the subjects were determined by real-time quantitative polymerase chain reaction (qPCR) targeting the beta-globin gene. The median plasma DNA concentrations of the NPC patients and control subjects were 122 copies/ml and 134 copies/ml, respectively. There was no significant difference between the plasma DNA concentrations of the two groups (p=0.708, Mann-Whitney test). For the study of the size distribution of plasma DNA, we developed a panel of nine qPCR reactions targeting the leptin gene with gradually increasing amplicon size ranging from 105 bp to 798 bp. The absolute concentrations of plasma DNA determined by the 105 bp system were not significantly different between the two groups. There was a good correlation between the concentrations determined by qPCR targeting leptin and beta-globin genes. The fractional concentration of each amplicon size was then calculated by dividing the absolute concentration by the concentration of the 105 bp amplicon. The results are shown in figure 1. The fractional concentrations were significantly higher in NPC patients than control subjects for amplicons size 201 bp or longer (p
Single Cell Transcriptomic Characterization of the Immune Microenvironment in Naturally Progressing Chronic Lymphocytic Leukemia (CLL)
Authors: Noelia Purroy, Jean Fan, Shuqiang Li, Laura Z. Rassenti, James A Lederer, Donna S Neuberg, Thomas J. Kipps, Peter Kharchenko, Catherine J. Wu
Journal: Blood (2018)
E‐cigarettes and Western Diet: Important Metabolic Risk Factors for Hepatic Diseases
Authors: Kamrul M. Hasan, Theodore C. Friedman, Xuesi Shao, Meher Parveen, Carl Sims, Desean L. Lee, Jorge Espinoza‐Derout, Indrani Sinha‐Hikim, Amiya P. Sinha‐Hikim
Journal: Hepatology (2019)

The use of electronic nicotine delivery systems (ENDS), also known as e‐cigarettes, with a variety of e‐liquids/e‐juices, is increasing at an alarming rate among adolescents who do not realize the potential harmful health effects. This study examines the harmful effects of ENDS on the liver. Apolipoprotein E null ( ApoE‐/‐ ) mice on a western diet (WD) were exposed to saline or ENDS with 2.4% nicotine aerosol for 12 weeks using our mouse ENDS exposure model system, which delivers nicotine to mice and leads to equivalent serum cotinine levels found in human cigarette users. ApoE‐/‐ mice on a WD exposed to ENDS exhibited a marked increase in hepatic lipid accumulation compared with ApoE‐/‐ on a similar diet exposed to saline aerosol. The detrimental effects of ENDS on hepatic steatosis were associated with significantly greater oxidative stress, increased hepatic triglyceride levels, and increased hepatocyte apoptosis, independent of adenosine monophosphate–activated protein kinase signaling. In addition, hepatic RNA sequencing analysis revealed that 433 genes were differentially expressed in ENDS‐exposed mice on WD compared with saline‐exposed mice. Functional analysis indicates that genes associated with lipid metabolism, cholesterol biosynthesis, and circadian rhythm were most significantly altered in the liver in response to ENDS. Conclusion : These results demonstrate profound adverse effects of ENDS on the liver. This is important information for regulatory agencies as they regulate ENDS.