tbuckley/cabot-search huggingface dataset:
Proteinase-activated receptor 1, 3 expression in primary human carcinoma cells
Authors: Wan-Zhou Xie, Martin Leibl, Michael R. Clark, Thomas Kunze, Peter Dohrmann, Michael Steiner, Frank Gieseler
Journal: Cancer Research (2005)

4894   The coagulation system is regularly activated in patients with cancer, especially with lung cancer and gastrointestinal tumors. Up to 30 % of these patients suffer from thromboembolic complications. Obviously, activation of thrombin occurs in the natural course of cancer. During tumor progression, many patients develop malignant effusions; treatment is complicated by increased resistance of tumor cells to chemotherapy. Thrombin-mediated activation of cellular receptor(s), such as proteinase-activated receptor-1(PAR-1), plays an important role in tumor growth, local progression, and distant metastasis. Our hypothesis is, that tumor cells that express PAR-1 have a survival benefit if they are activated by thrombin within the malignant effusion. We harvested primary cancer cells from pleural and peritoneal effusions of 110 patients with different carcinomas. In 22 cases we were able to establish long time cultures (2 pancreatic, 4 colon, 3 SCLC, 5 NSCLC, 3 mesothelioma, 1 gastric, 1 rectum, 1 breast, 1 melanoma and 1 NHL). We detected PAR-1, 3 expression using reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence activated cell sorting (FACS) scan. We found that in 76% the primary cancer cells were PAR-1 positive using RT-PCR assays, and in 70% the expression of PAR-1 receptor was positive using FACS scan. In contrast, we found that PCR for PAR-3 was positive in only 37.5% and the expression of the receptor in 6%. As a sign of thrombin activation, we regularly found increased levels of prothrombin fragment F1+2 in the malignant effusions compared to serum of patients (12.0 +/− 4.1 nmol/L vs 1.9 +/− 0.4 nmol/L). In summary, we found that most of the primary cancer cells in malignant effusions exhibit a positive PAR-1 expression, but PAR-3 expression is low. Also, thrombin is activated in most malignant effusions as shown by prothrombin fragment 1+2 elevation. Further experiments will show if these cell-biological mechanisms aggravate cellular resistance in primary tumor cells found in malignant effusion in end-stage cancer. Therapeutic consequences, such as therapeutic thrombin inhibition in addition to chemotherapy are discussed.
Fidaxomicin versus oral vancomycin for severe Clostridium difficile infection: a retrospective cohort study
Authors: C.A. Gentry, P.K. Nguyen, S. Thind, G. Kurdgelashvili, G.H. Skrepnek, R.J. Williams
Journal: Clinical Microbiology and Infection (2018)

This study was conducted to compare clinical outcomes of fidaxomicin versus oral vancomycin in the management of severe Clostridium difficile infection (CDI).The investigation was a retrospective, multicentre, propensity score-matched analysis using a national clinical administrative database. Veterans treated for severe CDI from any Veterans Affairs Medical Center between 1 June 2011 and 30 June 2017 were included if they received fidaxomicin or an oral vancomycin regimen for treatment. The two groups were matched by the nearest-neighbour method from a propensity score derived from independent variables associated with the selection of a fidaxomicin course.Propensity score matching resulted in two well-matched cohorts consisting of 213 fidaxomicin and 639 oral vancomycin courses. No statistically-significant difference was found for the primary outcome of combined clinical failure or recurrence (68/213 (31.9%) versus 163/639 (25.5%), respectively, p 0.071). Additionally, no statistically significant differences were found for the secondary outcomes of 30-day (23/213 (10.8%) versus 75/639 (11.7%), respectively, p 0.71), 90-day (48/213 (22.5%) versus 140/639 (21.9%), respectively, p 0.85), and 180-day mortality (62/213 (29.1%) versus 186/639 (29.1%), respectively, p 1.0) between the two treatment groups.Courses of fidaxomicin or oral vancomycin for severe CDI resulted in similar treatment outcomes. Study findings are consistent with current treatment guideline recommendations for the use of either agent in the management of severe CDI.
Efficacy and safety of switching to ixekizumab in secukinumab nonresponder patients with psoriasis: results from a multicentre experience
Authors: A. Conti, F. Peccerillo, P. Amerio, A. Balato, F. Bardazzi, L. Bianchi, M. Burlando, S.P. Cannavò, A. Chiricozzi, P. Dapavo, C. De Simone, M.C. Fargnoli, A. Gambardella, P. Gisondi, P. Malagoli, G. Malara, C. Mugheddu, A.M. Offidani, S. Piaserico, F. Prignano, L. Stingeni, G. Pellacani
Journal: British Journal of Dermatology (2018)
Abstract 18555: Endothelial Microparticles Induced by TNF-α Vary in miRNA Content and Physical Properties: Implications for Their Role in Cell-to-Cell Communication
Authors: Tamas Alexy, Kimberly Rooney, Martina Weber, Charles D Searles
Journal: Circulation (2014)

Introduction: Endothelial microparticles (EMPs) have traditionally been considered to be markers of inflammation and endothelial dysfunction; they have been shown to disrupt vascular homeostasis an...
Type 2 Diabetes Presenting With Persistent Chorea
Authors: Mayur Chalia, Thyagarajan Subramanian
Journal: JAMA Neurology (2018)

A man in his late 60s with a diagnosis of type 2 diabetes for more than 10 years that was complicated by neuropathy and retinopathy presents with persistent chorea in the left upper extremity for about 1 month despite aggressive correction with insulin. What is your diagnosis?
Inhalation of combustion-derived air pollution impairs endogenous fibrinolysis in patients with ischemic heart disease
Authors: N L Mills, H Tornqvist, M Gonzalez, S D Robinson, A E Finlayson, W MacNee, F R Cassee, A Blomberg, T Sandstrom, N A Boon, K Donaldson, D E Newby
Journal: Journal of the American College of Cardiology (2006)
Detection of novel mutations associated with independent resistance and cross-resistance to isoniazid and prothionamide in Mycobacterium tuberculosis clinical isolates
Authors: M.M. Islam, Y. Tan, H.M.A. Hameed, Z. Liu, C. Chhotaray, Y. Liu, Z. Lu, X. Cai, Y. Tang, Y. Gao, G. Surineni, X. Li, S. Tan, L. Guo, X. Cai, W.W. Yew, J. Liu, N. Zhong, T. Zhang
Journal: Clinical Microbiology and Infection (2018)
Abstract 17548: Low Serum Triglyceride Level and Low Body Mass Index Associate Increased Risk of Long-term Cardiovascular Mortality in Patients Undergoing Percutaneous Coronary Intervention, 20 Years Follow-up
Authors: Shinichiro Doi, Hiroshi Iwata, Ryo Naito, Hirohisa Endo, Hideki Wada, Hirokazu Konishi, Shuta Tsuboi, Manabu Ogita, Yoshiteru Kato, Tomotaka Dohi, Takatoshi Kasai, Hiroshi Tamura, Shinya Okazaki, Katsumi Miyauchi, Hiroyuki Daida
Journal: Circulation (2016)

Introduction: Increased risk of adverse cardiovascular events in patients with low body mass index (BMI) undergoing percutaneous coronary intervention (PCI) has been reported as “obesity paradox”. ...
Abstract 14850: An Educational Intervention Reduces the Rate of Inappropriate Echocardiograms Ordered on an Inpatient Medical Service
Authors: Rajan S Bhatia, Michael H Picard, Creagh E Milford, Rory B Weiner
Journal: Circulation (2012)

Background: Appropriate Use Criteria (AUC) for transthoracic echocardiography (TTE) was developed in response to concerns about inappropriate utilization of TTE. Our aim was to prospectively study the impact of an AUC-based educational intervention on TTE ordering among housestaff on the inpatient General Internal Medicine Service at an academic medical center. Methods: We conducted a prospective, time series analysis of an educational intervention designed to reduce inappropriate TTE ordering from February-May 2012, which was compared to TTE ordering on the same general medical service during a control period (February-May 2011). The intervention consisted of: 1) a lecture to housestaff on the 2011 AUC for TTE, 2) a pocketcard that applies the AUC to common clinical scenrarios and, 3) bimonthly feedback on ordering behavior via email. The primary outcome was the proportion of inappropriate and appropriate TTEs ordered during the intervention period. Results: 98.2% of all TTEs ordered in the control and s...
Taking the bull by the horn: the frontline use of infliximab for the treatment of immune checkpoint inhibitor-induced enterocolitis
Authors: Khashayar Esfahani
Journal: Journal for ImmunoTherapy of Cancer (2018)

Immune checkpoint inhibitors which activate the host’s immune system to fight cancer have brought dramatic improvements to the overall survival of a growing number of deadly malignancies. Their use comes at the expense of often serious immune-related adverse events which consist of an off-target attack of the immune system on potentially any of the human body’s healthy organs. For lack of better-validated evidence, and regardless of the organ affected, clinicians often use the same immunosuppressive regimens consisting of high dose corticosteroids followed by the introduction of biologic agents such as the tumor-necrosis alpha inhibitor infliximab for corticosteroid-refractory toxicities. The article by Johnson et al. is timely in providing a more personalized approach for the management of immune-related toxicities affecting the lower digestive tract with many positive clinical outcomes associated with the upfront use of infliximab in association with corticosteroids. This commentary will provide a narrative summary of their findings in light of the current clinical knowledge relevant to the understanding of immune-related enterocolitis.
Sargassum seaweed on Caribbean islands: an international public health concern
Authors: Dabor Resiere, Ruddy Valentino, Rémi Nevière, Rishika Banydeen, Papa Gueye, Jonathan Florentin, André Cabié, Thierry Lebrun, Bruno Mégarbane, Gilles Guerrier, Hossein Mehdaoui
Journal: The Lancet (2018)
Abstract 19556: Mortality and Morbidity Outcomes Based on Affected Coronary Region in Patients With Acute Myocardial Infraction
Authors: Saman Setareh-Shenas, Di Pan, Sung Lee, Nader Ishak Gabra, Eyal Herzog
Journal: Circulation (2017)

Background: Data on morbidity and mortality on acute myocardial infarction (AMI) based on coronary region is obtained from studies conducted over three decades ago. The aim of this study is to evaluate morbidity and mortality outcomes, in respect to coronary anatomy region in one of the largest public national databases available. Methods: This is a retrospective analysis based on the 2014 Nationwide Inpatient Sample, the largest publicly available inpatient database in the U.S. Patients older than 18 years and with primary diagnosis of AMI were included in the analysis. Primary outcome was mortality. Secondary outcomes include ICU admission, and cardiogenic shock. Multivariate regression analyses were performed to test for independent associations between outcomes and variables of interest. Diagnoses and procedures were identified using ICD-9-CM codes. Analysis was performed using Stata 14.2. Results: We identified a total of 612,575 patients with a primary diagnosis of AMI. Among these patients 2.2% had...
Abstract 18351: Improving Reproducibility of Left Ventricular Ejection Fraction by 5/6 Area-length Method in a Pediatric Echocardiographic Laboratory - A Quality Improvement Initiative
Authors: Hollie Carron, Kimberly Reid, Anitha Parthiban
Journal: Circulation (2017)

Introduction: Reliable echocardiographic assessment of left ventricular (LV) size and ejection fraction (EF) is critical to the management of multiple medical conditions in children. Studies suggest that >10% variation can occur in EF measurement by 2-dimensional echocardiography due to inter-observer variability (IOV). Hypothesis: We hypothesized that IOV for LV EF and volumes by the 5/6 area -length method can be improved by systematic implementation of quality improvement interventions designed to standardize image acquisition and measurement. Methods: Sonographers were graded on quality of image acquisition (maximum score = 10) by review of 3 random studies and on measurement technique (maximum score =12) by measuring the same 5 sets of images blinded to each other. Data were obtained at baseline, after a general teaching session and following a second teaching session along with individual training for sonographers with lower score. To assess IOV, difference from an expert reader (cardiologist) was c...
Leukemic Cell Expressing a Novel Kinase Fusion Protein NCOR1-LYN Exhibits High Sensitivity to Dasatinib and Rapamycin
Authors: Toshihiro Tomii, Toshihiko Imamura, Mio Yano, Kenichi Sakamoto, Itaru Kato, Kuniaki Tanaka, Takashi Mikami, Makiko Morita, Souichi Adachi, Junko Takita, Nobutaka Kiyokawa, Keizo Horibe, Hajime Hosoi
Journal: Blood (2018)
SP0119 The evolving role of mepolizumab in egpa
Authors: F. Moosig
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> There is overwhelming evidence that eosinophiles play a key role in the pathogenesis of EGPA. Il-5 is the central cytokine for eosinophil maturation, eosinophil release from the bone marrow and eosinophil survival. Mepolizumab is an antibody neutralising IL-5, which proved efficient in the hypereosinophilic syndrome and eosinophilc asthma, amongst other conditions. Targeting this cytokine in EGPA therefore seemed plausible. Two small uncontrolled trials demonstrated the safety of mepolizumab in EGPA and indicated the potential for induction of remission, maintenance and steroid sparing. A randomised controlled trial (MIRRA) confirmed those findings and showed higher rates of accrued remission for mepolizumab when given as ad-on medication to conventional immunosupressants and/or glucocorticoids. Steroid sparing properties were also confirmed. MIRRA and previous trials in different indications issued no major safety concerns. Based on this trial drug approval for EGPA might be feasible. To date the major problems in the treatment of EGPA are 1) refractory disease 2) a high frequency of relapses and 3) the need for high glucocorticoid doses in many patients. Mepolizumab could be used for induction of remission in addition to glucocorticoids. However, its not yet clear, which subgroup of patients might profit most. Especially patients with severe disease have not been investigated. For patients with refractors non-severe disease mepolizumab is a potential option. Mepolizumab also was efficient in preventing relapses and therefore may also be used for maintenance of remission, especially in patients suffering from prevalent relapses. Finally, patients with high need for glucococrticoids could profit from mepolizumab, particularly in case of steroid-sensitive comorbidities or steroid-induced complications. <h3>Disclosure of Interest</h3> F. Moosig Consultant for: Chugai, GSK
Abstract 18611: Sex Differences in the Influence of Body Mass Index on Incidence of Atrial Fibrillation: The Tromsø Study 1979-2013
Authors: Jocasta Ball, Maja-Lisa Løchen, Tom Wilsgaard, Henrik Schirmer, Laila A Hopstock, Bente Morseth, Ellisiv B Mathiesen, Inger Njølstad, Sweta Tiwari, Simon Stewart, Ekaterina Sharashova
Journal: Circulation (2017)

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia and imparts substantial burden. Prevalence is increasing in parallel with aging, improved survival and emerging epidemic...
Electrocardiography Screening for Atrial Fibrillation—Reply
Authors: Susan J. Curry, Alex H. Krist, Douglas K. Owens
Journal: JAMA (2018)

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Rigorous control of vesicle-forming lipid pKa by fluorine-conjugated bioisosteres for gene-silencing with siRNA
Authors: Ayaka Okamoto, Hiroyuki Koide, Naoki Morita, Yusuke Hirai, Yuji Kawato, Hiromichi Egami, Yoshitaka Hamashima, Tomohiro Asai, Takehisa Dewa, Naoto Oku
Journal: Journal of Controlled Release (2018)
Effects of Anti–Helicobacter pylori Therapy on Incidence of Autoimmune Diseases, Including Inflammatory Bowel Diseases
Authors: Kun-Der Lin, Guei-Fen Chiu, Akbar K. Waljee, Stephanie Y. Owyang, Mohamad El-Zaatari, Shrinivas Bishu, Helmut Grasberger, Min Zhang, Deng-Chyang Wu, John Y. Kao
Journal: Clinical Gastroenterology and Hepatology (2018)
Chronic Intermittent Hypoxia effects are not mediated by guinea pig carotid body sensitization
Authors: Angela Gomez-Niño, Inmaculada Docio, Elena Olea, Jesus Prieto-Lloret, Ana Obeso, Asuncion Rocher
Journal: European Respiratory Journal (2018)

Resumen del trabajo presentado al European Respiratory Society (ERS) International Congress, celebrado en Paris (Francia) del 15 al 19 de septiembre de 2018.
Inhibition of Dipeptidyl Peptidase-4 Accelerates Epithelial–Mesenchymal Transition and Breast Cancer Metastasis via the CXCL12/CXCR4/mTOR Axis
Authors: Fan Yang, Yuta Takagaki, Yasuo Yoshitomi, Takayuki Ikeda, Jinpeng Li, Munehiro Kitada, Asako Kumagai, Emi Kawakita, Sen Shi, Keizo Kanasaki, Daisuke Koya
Journal: Cancer Research (2018)

Dipeptidyl peptidase (DPP)-4 is a multifunctional glycoprotein involved in various biological and pathologic processes. DPP-4 has been widely recognized as a therapeutic target for type 2 diabetes mellitus but is also implicated in the development of human malignancies. Here, we show that inhibition of DPP-4 accelerates breast cancer metastasis via induction of CXCL12/CXCR4, which activates mTOR to promote epithelial-mesenchymal transition (EMT). In cultured cells, DPP-4 knockdown induced EMT and cell migration. Treatment with the DPP-4 inhibitor KR62436 (KR) promoted primary tumor growth and lung metastasis in a 4T1 tumor allograft mouse model; DPP-4 knockdown in 4T1 cells displayed similar phenotypes in vivo and in vitro. KR treatment enhanced the levels of CXCL12/CXCR4 and phosphorylated mTOR, which were associated with the induction of EMT in metastatic cancer cells. KR-induced EMT in cancer cells was inhibited by treatment with the CXCR4 inhibitor AMD3100 or the mTOR inhibitor rapamycin, and AMD3100 suppressed KR-induced metastasis in vivo. Our findings suggest that DPP-4 plays a significant role in cancer biology and that inhibition of DPP-4 promotes cancer metastasis via induction of the CXCL12/CXCR4/mTOR/EMT axis. SIGNIFICANCE: These findings reveal that inhibition of DPP-4 increases the metastatic potential of breast cancer. This is especially important given the potential use of DPP-4 inhibition as a therapeutic strategy for type 2 diabetes.
Tremelimumab in Combination With Microwave Ablation in Patients With Refractory Biliary Tract Cancer
Authors: Changqing Xie, Austin G. Duffy, Donna Mabry‐Hrones, Bradford Wood, Elliot Levy, Venkatesh Krishnasamy, Javed Khan, Jun S. Wei, David Agdashian, Manoj Tyagi, Vineela Gangalapudi, Suzanne Fioravanti, Melissa Walker, Victoria Anderson, David Venzon, William D. Figg, Milan Sandhu, David E. Kleiner, Maria Pia Morelli, Charalampos S. Floudas, Gagandeep Brar, Seth M. Steinberg, Firouzeh Korangy, Tim F. Greten
Journal: Hepatology (2018)

Treatment options for patients with advanced biliary tract cancer are limited. Dysregulation of the immune system plays an important role in the pathogenesis of biliary tract cancer (BTC). This study aimed to investigate whether tremelimumab, an anti‐CTLA4 (cytotoxic T‐lymphocyte–associated protein 4) inhibitor, could be combined safely with microwave ablation to enhance the effect of anti‐CTLA4 treatment in patients with advanced BTC. Patients were enrolled to receive monthly tremelimumab (10 mg/kg, intravenously) for six doses, followed by infusions every 3 months until off‐treatment criteria were met. Thirty‐six days after the first tremelimumab dose, patients underwent subtotal microwave ablation. Interval imaging studies were performed every 8 weeks. Adverse events (AEs) were noted and managed. Tumor and peripheral blood samples were collected to perform immune monitoring and whole‐exome sequencing (WES). Twenty patients with refractory BTC were enrolled (median age, 56.5 years). No dose‐limiting toxicities were encountered. The common treatment‐related AEs included lymphopenia, diarrhea, and elevated transaminases. Among 16 patients evaluable for efficacy analysis, 2 (12.5%) patients achieved a confirmed partial response (lasting for 8.0 and 18.1 months, respectively) and 5 patients (31.3%) achieved stable disease. Median progression free survival (PFS) and overall survival (OS) were 3.4 months (95% confidence interval [CI], 2.5‐5.2) and 6.0 months (95% CI, 3.8‐8.8), respectively. Peripheral blood immune cell subset profiling showed increased circulating activated human leukocyte antigen, DR isotype ([HLA‐DR] positive) CD8+ T cells. T‐cell receptor (TCR)β screening showed tremelimumab expanded TCR repertoire, but not reaching statistical significance (P = 0.057). Conclusion: Tremelimumab in combination with tumor ablation is a potential treatment strategy for patients with advanced BTC. Increased circulating activated CD8+ T cells and TCR repertoire expansion induced by tremelimumab may contribute to treatment benefit.
The genetics and clinical characteristics of children morphologically diagnosed as acute promyelocytic leukemia
Authors: Jie Zhao, Jian-Wei Liang, Hui-Liang Xue, Shu-Hong Shen, Jing Chen, Yan-Jing Tang, Li-Sha Yu, Huan-Huan Liang, Long-Jun Gu, Jing-Yan Tang, Ben-Shang Li
Journal: Leukemia (2018)
CD30-Chimeric Antigen Receptor (CAR) T Cells for Therapy of Hodgkin Lymphoma (HL)
Authors: Carlos A. Ramos, Mrinalini Bilgi, Claudia P. Gerken, Olga Dakhova, Zhuyong Mei, Bambi J. Grilley, Adrian P. Gee, Cliona M. Rooney, Gianpietro Dotti, Barbara Savoldo, Helen E. Heslop, Malcolm K. Brenner
Journal: Blood (2018)
Socioeconomic Disparities and Health Outcomes
Authors: Rameela Chandrasekhar
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

5 consecutive years.Moreover, the age of the study subjects does not influence the serum sRAGE levels.Indeed, our data show no differences in serum sRAGE levels between young (average 23.5 yr) and old (average 54.7 yr) subjects in either the never-smokers group or the smokers group (Figure 1B).In addition, our young subjects were even younger than the study population of Biswas, which had an average age of 34.1 years.Our data therefore indicate that neither age nor chronic smoke exposure affects serum sRAGE levels.The discrepancy in study results when comparing the serum sRAGE levels in smokers and nonsmokers may be explained by our finding that smoking before blood sampling acutely decreases serum sRAGE levels (1).Therefore, controlling or monitoring smoking behavior before blood sampling may be used as a precautionary measure to decrease the variability between measurements and increase the value of sRAGE as a biomarker for COPD.Lastly, we agree with Biswas that more research is needed regarding the effect of smoking on serum sRAGE levels and the underlying mechanisms before sRAGE can be clinically used as a biomarker for COPD.