tbuckley/cabot-search huggingface dataset:
Abstract 11890: S100A8/A9 is Increased in Psoriasis Serum, Relates to Vascular Diseases and Activates Human Endothelial Cells
Authors: Heather Teague, Qimin Ng, Monica Purmalek, Balaji Natarajan, Taufiq Salahuddin, Elena Stansky, Tarek Aridi, Martin P Playford, Mariana J Kaplan, Nehal N Mehta
Journal: Circulation (2015)

Introduction: Psoriasis is a chronic inflammatory disorder of the skin affecting 2-4% of the population and is associated with an increased risk of cardiovascular events, specifically myocardial infarction. Methods: In a large, ongoing prospective cohort study of psoriasis and cardiovascular diseases (NCT01778569), we studied a consecutive sample (n=100) and aimed to investigate the potential role that S100A8/A9 may have in linking psoriasis to CV disease measured by FDG PET CT and coronary CTA. Furthermore, we conducted in vitro experiments on human aortic endothelial cells (ECs) to examine whether treatement with S100A9 activates these cells. We hypothesized that S100A8/A9 would relate to psoriasis severity, relate to in vivo vascular inflammation by FDG PET CT, non-calcified burden of coronary disease by CCTA and increase endothelial cell activation. Results: We observed that the S100A8/A9 heterodimer was elevated in serum (mean psoriasis: 2019 ± 100.1; non-psoriasis: 1634 ± 160.7; p = 0.02), correlating both with psoriasis severity score (adjusted β = 0.53, p = 0.02) and overall aortic vascular inflammation measured by FDG PET CT (adjusted β = 0.48, p = 0.02) beyond the Framingham Risk Score. Additionally, we found that S100A8/A9 was associated with direct coronary atherosclerosis measured by coronary CTA demonstrating an increase in total (β = 0.16, p = 0.04) and non-calcified plaque burden (β = 0.23, p = 0.003) but not dense calcified burden. When EC's were treated with S100A9, ICAM1, E-Selectin and VCAM1 gene expression levels increased 10-fold (p = 0.001), 86-fold (P = 0.007) and 20-fold (p = 0.0002) respectively compared to the untreated human aortic endothelial cells. Conclusions: S100A8/A9 related to psoriasis severity, in vivo vascular inflammation, non-calcified plaque in the coronary arteries and EC activation. These findings suggest this protein may play a role in linking psoriasis to CVD and a role in early atherosclerotic plaque formation. Ongoing studies aim to elucidate the source of S100A8/A9 in the blood and to characterize the signaling pathway utilized by S100A8/A9 to understand whether this pathway is broadly applicable to vascular diseases associated with chronic inflammation.
Thoracic ultrasound can be a trustable tool in untouchable lung nodule surgery
Authors: H. Zhang
Journal: Annals of Oncology (2019)

Background: Localization of ground-glass opacifications (GGOs) with more than 1cm distance to the pleura are still a challenge to thoracic surgeons during video-assisted thoracoscopic surgery (VATS). Efficiency, damage avoidance, and safety are uppermost factors to be considered when choosing the location technique. Our center tested the thoracoscopic ultrasound (US) as a complementary method during VATS GGOs surgery. Methods: We evaluated 40 patients with GGOs divided into group A (VATS-US) and group B (VATS). We used positive pressure in the chest cavity during surgery in group A to decrease the time needed to collapse the lung. With the same excision standard between the two groups, we recorded and compared the time needed, ratio of converting to thoracotomy, blooding volume, and any complications observed. Results: We found that the use of ultrasound during VATS surgery could improve the success rate of localization (p < 0.05), especially in patients where it was difficult to conduct preoperative CT guided localization (p < 0.01). There were no statistically significant differences between the two groups in operation time, bleeding during the operation, or postoperative complications (p > 0.05). Conclusions: We concluded that thoracoscopic ultrasound could be an excellent supplement to preoperative CT localizing technique for localization of GGOs, if not a replacement at present. Legal entity responsible for the study: Hongbin Zhang. Funding: Peking University International Hospital. Disclosure: The author has declared no conflicts of interest.
FRI-353-Metabolic implications of methionine adenosyltransferase 1A depletion during fasting
Authors: David Fernández Ramos, Laura Mosca, Naroa Goikoetxea, Marina Serrano-Macia, Teresa Cardoso Delgado, Fernando Lopitz Otsoa, Virginia Gutiérrez de Juan, Diego Saenz de Urturi, Francisco Gonzalez-Romero, Asier Ruiz-Nuñez, Juan Falcon-Perez, Ashwin Woodhoo, Patricia Apichueta, Shelly C. Lu, José M. Mato, María Luz Martínez-Chantar, Marta Varela-Rey
Journal: Journal of Hepatology (2019)
Lung tumorspheres as a drug screening platform against cancer stem cells
Authors: A. Herreros Pomares, H. Amado, S. Calabuig Fariñas, E. Escorihuela, J. Murga, S. Torres, E. Durendez-Saez, F. Zhang, A. Blasco, A. Navarro, C. Sampedro, E. Jantus-Lewintre, C. Camps
Journal: Annals of Oncology (2019)

Background: Treatment resistance and metastasis are linked to cancer stem cells (CSCs). This population represents a promising target, but remains unexplored in lung cancer. The main objective of this study was to characterize lung CSCs and discover new therapeutic strategies. Methods: The study was performed on NSCLC cells from 8 resected patients and 12 cell lines. Suspension cultures (tumorspheres) were established for CSCs enrichment and differentiated tumor cells were cultured as monolayers (2D). The CSCs properties of tumorspheres were assessed in vitro and in vivo. The expression of 60 CSC-related genes was analyzed by RTqPCR and the expression of 12 proteins was evaluated by immunoblot (IB) and immunofluorescence (IF). High-throughput screening was performed using Prestwick and Myria libraries. Selected drugs were administered intraperitoneally to NOD/SCID mice with tumors induced by NSCLC patient and H1650 tumorspheres. Results: Lung tumorspheres showed unlimited exponential growth (>30 passages), great tumor initiation potential, differentiation capacity, and high resistance to chemotherapy agents, but not to salinomycin. Tumorspheres had significantly higher expression of CSC-related genes (ALDH1A1, KLF4, NANOG, CD44, CD90, CDKN1A, JUNB, MDM2), invasion promoters (MMP9, SNAI1, ITGA6), and Notch (NOTCH1, NOTCH3, DLL4, JAG1) and Wnt (CTNNB1, GSK3B) components than their paired adherent-cultured cells. IB confirmed the overexpression of proteins encoded by CD44, NANOG, CDKN1A, SNAI1, ITGA6, and NOTCH3, and IF showed different localization patterns on lung adenocarcinoma tumorspheres compared with the 2D cultures. Three novel drugs [Disulfiram (DSF), Compound 1 (COMP1) and Compound 2 (COMP2)] with greater cytotoxic potential against lung tumorspheres than monolayer cells were identified. These results were validated in vivo, demonstrating the capacity of these drugs to reduce tumor growth in mice. Conclusions: Tumorspheres are a useful culture platform for CSCs characterization in a simple and cost-effective way. We found three drugs which are able to diminish the formation and viability of tumorspheres, constituting promising therapies against lung CSCs. Supported by CB16/12/00350, PI12-02838, and PI15-00753 from ISCIII. Legal entity responsible for the study: Fundación de Investigación Hospital General Universitario de Valencia. Funding: Centro de Investigación Biomédica en Red de Oncología (CIBERONC) and Instituto de Salud Carlos III (ISCIII). Disclosure: All authors have declared no conflicts of interest.
Abstract 20439: Generation of Novel Fluorescent Reporter Cells and Transgenic Mice for Identification and Characterization of Cardiomyocytes Derived From Adrenergic Progenitor Cells
Authors: Jixiang Xia, Celines Martinez, Karl Pfeifer, Steven Ebert
Journal: Circulation (2010)

Intrinsic cardiac adrenergic cells contribute to pacemaking, conduction, and working myocardium during prenatal heart development. To study these cells, we generated knock-in transgenic mice that e...
LBP-24-Safety, tolerability and efficacy of volixibat, an apical sodium-dependent bile acid transporter inhibitor, in adults with nonalcoholic steatohepatitis: 24-week interim analysis results from a phase 2 study
Authors: Philip Newsome, Melissa Palmer, Bradley Freilich, Muhammad Sheikh, Aasim Sheikh, Harry Sarles, Robert Herring, Parvez Mantry, Zeid Kayali, Tarek Hassanein, Yi Chen, Guruprasad Aithal
Journal: Journal of Hepatology (2019)
Abstract 12445: A Detailed Analysis of Peripheral Blood Cytokines 2-3 weeks After Acute Myocardial Infarction: IL-6-Related Impairment of Bone Marrow Function
Authors: Mahan Shahrivari, Elizabeth Wise, Doris A Taylor, Carl J Pepine, Timothy D Henry, Jay H Traverse, John P Cooke, Roberto Bolli, Christopher R Cogle
Journal: Circulation (2015)

Background: Intracoronary infusion of bone marrow (BM) mononuclear cells (BM-MNCs) late after acute myocardial infarction (AMI) has shown no improvement in global or regional left ventricular (LV) function (LateTIME and SWISS-AMI). Studies in experimental AMI models suggest a possible cytokine-related depression of progenitor cell function. Furthermore, BM cell content is correlated with the LV functional response. Accordingly, we hypothesize that inflammatory cytokines associated with the late phase of AMI may impair BM function and alter progenitor cell subsets. Method: Patients with previous AMI (n=87) were recruited in a multicenter cell therapy trial by the Cardiovascular Cell Therapy Research Network (CCTRN LateTIME, NCT00684060). BM and peripheral blood (PB) were collected 2-3 weeks after AMI and examined for cell phenotypes and progenitor capacities as well as PB inflammatory and angiogenic cytokines in a core laboratory. Multiple regression analyses were conducted and correlations between cytokine levels and cell phenotypes, cell functions, and post-MI cardiac function were determined. BM from healthy donors, handled in the same manner, was used as a reference. Result: Of 26 cytokines analyzed, IL-6 showed a negative correlation with ECFC colony maximum in BM (estimate±SE (SEE) -0.13±0.04 P=0.007, multivariableR2: 0.59) and Healthy BM showed decreased ECFC colony outgrowth in the presence of IL-6 (P &lt;0.05), in a dose-dependent manner. PDGF-BB positively correlated with CFU-EC colony maximum in BM (SEE 0.006± 0.002, P=0.023, R2: 0.22), MSC colony maximum in BM (SEE 0.006±0.002, P=0.023, R2: 0.17) and MSC colony maximum in PB (SSE 0.018±0.005, P=0.00005, R2:0.24). No significant correlations were found between cardiac function after AMI and PB cytokine levels. Conclusions: At 2-3 weeks after AMI, PB levels of the angiogenic cytokine, PDGF-BB and the pro-inflammatory cytokine, IL-6, were associated with BM cell phenotype and function. IL-6 has the potential to impair endothelial progenitor cell capacity; inhibiting IL-6 may be a target for improving the regenerative capacity of BM cells after AMI.
Treatment of metastatic bone tumors in the pelvis with bipolar radiofrequency ablation with and without PMMA cement placement.
Authors: Andrew Bruner, Melissa Potts, Michael Schacht, Mary Hubert, Martin Sven Vyleta, Goetz Kloecker, Vivek R. Sharma, Rebecca A. Redman, Douglas M. Coldwell
Journal: Journal of Clinical Oncology (2015)

e20543 Background: Boney metastatic disease is common in many tumors but predominantly in renal cell cancer, lung cancer, prostate, and breast cancer. Systemic therapy is effective in treating most as well as localized radiation therapy. However, approximately 30-40% of patients do not receive benefit from these modalities and direct treatment of the tumors causing pain is then indicated. Methods: Review of 58 patients (26 women, 32 men), mean age 62 years (range 41-83 yo.) had locoregional directed treatment of bone metastases from a variety of tumors was reviewed. These patients had metastatic disease to the pelvic bones (56) and to the sternum (2). Both lytic (47) and blastic metastases were evaluated for efficacy of the use of a purpose designed bipolar radiofrequency tumor ablation device for bone tumors (DFINE, Inc., San Jose, CA). After treatment with RFA, the lytic tumors were filled with PMMA cement while the blastic tumors were too dense to allow cement to be utilized. Results: In all cases, initial pain scores, mean 8/10 (range 5-10), and 2 hours after the procedure the pain scores had dropped to 2/10 mean (range 0-4). Further improvements were seen over time with the mean pain scores dropping to 1.8 after one week and 1 after one month. No complications causing increased level of care were noted. The further deacrease in the pain scores was likely due to the healing of the skin, muscle, and bone puncture sites to treat the tumors. Conclusions: This treatment is an effective and safe method for treating extra-vertebral metastases.
Proteomics-Derived Biomarker Panel Improves Diagnostic Precision to Classify Endometrioid and High-grade Serous Ovarian Carcinoma
Authors: Dylan Z. Dieters-Castator, Peter F. Rambau, Linda E. Kelemen, Gabrielle M. Siegers, Gilles A. Lajoie, Lynne-Marie Postovit, Martin Köbel
Journal: Clinical Cancer Research (2019)

Ovarian carcinomas are a group of distinct diseases classified by histotypes. As histotype-specific treatment evolves, accurate classification will become critical for optimal precision medicine approaches.To uncover differences between the two most common histotypes, high-grade serous (HGSC) and endometrioid carcinoma, we performed label-free quantitative proteomics on freshly frozen tumor tissues (HGSC, n = 10; endometrioid carcinoma, n = 10). Eight candidate protein biomarkers specific to endometrioid carcinoma were validated by IHC using tissue microarrays representing 361 cases of either endometrioid carcinoma or HGSC.More than 500 proteins were differentially expressed (P < 0.05) between endometrioid carcinoma and HGSC tumor proteomes. A ranked set of 106 proteins was sufficient to correctly discriminate 90% of samples. IHC validated KIAA1324 as the most discriminatory novel biomarker for endometrioid carcinoma. An 8-marker panel was found to exhibit superior performance for discriminating endometrioid carcinoma from HGSC compared with the current standard of WT1 plus TP53 alone, improving the classification rate for HGSC from 90.7% to 99.2%. Endometrioid carcinoma-specific diagnostic markers such as PLCB1, KIAA1324, and SCGB2A1 were also significantly associated with favorable prognosis within endometrioid carcinoma suggesting biological heterogeneity within this histotype. Pathway analysis of proteomic data revealed differences between endometrioid carcinoma and HGSC pertaining to estrogen and interferon signalling.In summary, these findings support the use of multi-marker panels for the differential diagnosis of difficult cases resembling endometrioid carcinoma and HGSC.
SAT-002-Lusutrombopag is a safe treatment option for thrombocytopenia in patients with chronic liver disease undergoing an invasive procedure: Pooled safety analysis from 3 studies
Authors: Nezam Afdhal, Robert Brown, Namiki Izumi, Takeshi Kano, Toshimitsu Ochiai, Masayuki Kurosaki, Francesco Violi, Pomy Shrestha
Journal: Journal of Hepatology (2019)
15 years of the Scandinavian knee ligament registries: lessons, limitations and likely prospects
Authors: Eric Hamrin Senorski, Eleonor Svantesson, Lars Engebretsen, Martin Lind, Magnus Forssblad, Jon Karlsson, Kristian Samuelsson
Journal: British Journal of Sports Medicine (2019)

High-quality national health registries provide the opportunities to: (1) improve patient outcomes by giving medical units and clinicians relevant feedback about their work; (2) detect inferior treatments and (3) identify prognostic factors associated with both good and bad outcomes. The Scandinavian knee ligament registries were established in 2004 and 2005, include data from 70 000 patients,1 and have led to more than 70 studies publications already (2019). This editorial reflects on lessons learnt, limitations identified and what the future may hold.

Two systematic reviews including all studies from the registries focused on factors associated with (1) additional anterior cruciate ligament (ACL) reconstruction and (2) patient-reported outcomes after ACL injury and reconstruction are summarised in table 1.2 3 

View this table:

Table 1 
Primary findings of the systematic reviews on the Scandinavian knee ligament registries



There is a balance in health registry studies between the large number of patients that decrease the type-II error (false negative) risk, and the multiple analyses and similar questions that are addressed which increase the type-I error (false positive) risk. Registry data are also susceptible to confounding interactions, some of which are unknown. Nevertheless, the registries produce results that reflect day-to-day practice owing to two key factors, a high rate of coverage (proportion of medical units who participate in relation to all eligible medical units) and completeness (proportion of target population in the registry). However, it must be remembered that the response rates from patient-reported follow-ups are a persistent challenge for health registries, where at …
SAT-154-Acute hemodynamic response to I.V propranolol during hepatic hemodynamic study in 26 cirrhotic patients with portal hypertention and nonbleeding esophageal varices. Correlation with esophageal bleeding and survival
Authors: Eyal Ashkenazi, Yulia Kovalev, Alex Haimovich, Eli Zuckerman
Journal: Journal of Hepatology (2019)
Challenges in the management of stage III non-small cell lung cancer (NSCLC) within multidisciplinary team (MDT): A lung cancer center experience
Authors: K. Harbegue, N. Mejri, H. El Benna, S. Labidi, N. Daoud, H. Boussen
Journal: Annals of Oncology (2019)

Background: We aimed to report patterns of care and difficulties during the management of patients with newly diagnosed stage III NSCLC who were presented at our MDT meeting. Methods: Medical records of 88 patients diagnosed with stage III NSCLC between 2011-2017 presented at least once at our weekly lung cancer MDT meeting, were reviewed. Tumor characteristics and treatment receipt were described. Results: Median age was 61 years old, with a disease stage: IIIA in 48 % and IIIB 52% before MDT meeting. We observed 27.3% of patients referred without histological diagnosis; median delay time from first visit to having a histological diagnosis was 17 days. Median time from first visit to presentation at MDT meeting was 11.8 days (SD = 15.3), and to the start of first therapy was 21.4 days (DS = 43.5). TNM stage was reconsidered after the MDT meeting in 16 % of cases. Treatment decision was upfront surgery in 20%, neoadjuvant chemotherapy (NACT) in 59 %, concurrent chemoradiation (CCRT) in 20%. MDT indications were in adherence to ESMO guidelines in 90 %. Treatment receipt was 81 % for surgery, 84% for NACT and 44% for CCRT. For NACT, the median delay between MDT presentation and start of therapy was 19 days, 15 days for surgery and 19 days for CCRT. Discordance between the planned and administered treatment was recorded in 58% of cases. The reasons for discordance were: 14% patient's refusal, 8% patient's general condition decline, 4% of cases for medical contraindications, 8% for the delay in radiation therapy initiation, and lost to follow up in 33 % of cases. Progression occurred during the planned treatment in 23% of cases and 10% of patients died before the end of the planned therapy. The MDT meeting was consulted for the same patient twice in 41% of cases, 3 times 1%. We observed a statistically significant difference between patients who had their treatment as decided by the MDT meeting with 49 months median overall survival versus 22 months in non-adherent patients (p < 0.01). Conclusions: Management of stage III NSCLC within a MDT showed a role in staging assessment and was characterized by a relatively rapid start of therapy and high impact on survival but a low receipt rate for CCRT. Legal entity responsible for the study: Medical Oncology Department Abderrahmen Mami Hospital. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
The world-wide burden of musculoskeletal diseases: a systematic analysis of the World Health Organization Burden of Diseases Database
Authors: Eden Sebbag, Renaud Felten, Flora Sagez, Jean Sibilia, Hervé Devilliers, Laurent Arnaud
Journal: Annals of the Rheumatic Diseases (2019)

Background Musculoskeletal (MSK) diseases are expected to have a growing impact worldwide. Objective To analyse the worldwide burden of MSK diseases from 2000 to 2015. Methods Disability-adjusted life years (DALYs), which combines the years of life lost (YLLs) and the years lived with disability (YLDs), were extracted for 183 countries from the WHO Global Health Estimates Database. We analysed the median proportion of DALYS, YLLs and YLDs for MSK diseases (ICD-10: M00–M99) among the 23 WHO categories of diseases. Mixed models were built to assess temporal changes. Results Worldwide, the total number of MSK DALYs increased significantly from 80,225,634.6 in 2000 to 107,885,832.6 in 2015 (p &lt; 0.001), with the total number of MSK YLDs increasing from 77,377,709.4 to 103,817,908.4 (p = 0.0008) and MSK diseases being the second cause of YLDs worldwide. YLLs due to MSK diseases increased from 2,847,925.2 to 4,067,924.2 (p = 0.03). In 2015, the median proportion of DALYs attributed to MSK diseases was 6.66% (IQR: 5.30 – 7.88) in Europe versus 4.66% (3.98 – 5.59) in the Americas (p &lt; 0.0001 vs Europe), 4.17% (3.14 – 6.25) in Asia (p &lt; 0.0001), 4.14% (2.65 – 5.57) in Oceania (p = 0.0008) and 1.33% (1.03 – 1.92) in Africa (p &lt; 0.0001). We observed a significant correlation (r = 0.85, p &lt; 0.0001) between the proportion of MSK DALYs and the gross domestic product per capita for the year 2015. Conclusions The burden of MSK diseases increased significantly between 2000 and 2015 and is high in Europe. These results are crucial to health professionals and policy makers to implement future health plan adjustments for MSK diseases.
Photodynamic therapy guidelines for the management of oral leucoplakia
Authors: Qianming Chen, Hongxia Dan, Fan Tang, Jiongke Wang, Xiaoying Li, Junxin Cheng, Hang Zhao, Xin Zeng
Journal: International Journal of Oral Science (2019)

With recent developments in photosensitizers and light delivery systems, topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) has become the fourth alternative therapeutic approach in the management of oral leucoplakia (OLK) due to its minimally invasive nature, efficacy, and low risk of systemic side effects and disfigurement. This report presents step-by-step guidelines for applying topical ALA-PDT in the management of OLK based on both the clinical experience of the authors and a systematic review of the current literature. Studies using protocols with standardized parameters and randomized clinical trials at multiple centres with adequate sample sizes and both interim and long-term follow-ups are needed before universally applicable guidelines can be produced in this field.
THU-293-Increased risk of advanced liver disease independently of classic metabolic risk factors or drug induced hepatotoxicity in patients with psoriasis
Authors: María Teresa Arias Loste, Paula Iruzubieta, Laura Rasines, Juan Carlos Rodriguez Duque, Jose Ignacio Fortea, Agustin Garcia, Angela Puente Sanchez, Susana Armesto, Javier Crespo
Journal: Journal of Hepatology (2019)