tbuckley/cabot-search huggingface dataset:
Abstract 12904: Ticagrelor Removal From Human Blood
Authors: George O Angheloiu, Bogdan G Gugiu, Rishikesh Pandey, Cristian Ruse, Cheryl Brooks, Ramachandra Dasari, Alyssa Hawranko, Carl Whatling
Journal: Circulation (2015)

Background: In acute coronary events, ticagrelor is recommended to be loaded prior to cardiac catheterization. In the PLATO study the rate of severe bleeding on ticagrelor in patients who needed urgent bypass graft surgery was high but similar for ticagrelor and clopidogrel. The reversible binding mode of action of ticagrelor onto the P2Y12 receptor provides an opportunity for drug removal not possible for the thienopyridines (clopidogrel and prasugrel) which are all irreversibly binding to P2Y12. Objective: Our goal was to devise an efficient method for ticagrelor removal from blood. Methods: Ticagrelor removal was measured in two sets of experiments. The first set was performed in a first-pass manner and used as drug vehicle bovine serum albumin (BSA) solution (0.4% and 4%), while the second set employed in three experiments blood either bought from BioreclamationIVT (older than 24 hours) or freshly collected from a healthy volunteer and mixed with ticagrelor at a concentration of approximately 5.1 ug/mL. BSA solution as well as blood carrying ticagrelor were passed at various velocities through columns containing two types of sorbent (Cytosorb and Porapak Q). Ticagrelor concentration was measured from the affluent and effluent solution using a liquid chromatography technique with tandem mass spectrometric detection LC/MS/MS). Results: Ticagrelor removal peaked at 99% and 100% using 40 mL Cytsorb and Porapak Q columns, respectively, during BSA experiments. The most efficient ticagrelor drug removal from blood was obtained with 260 mL sorbent (113 g of Cytosorb), with a peak removal from whole blood of 100% and 99% from blood cells during a 10-hour recirculating experiment reaching blood and plasma levels of 15 and 2 ng/mL, respectively, much below the ticagrelor platelet aggregation inhibition IC50 levels (30 ng/mL). Cytosorb has been also shown to absorb in bench experiments 99% of dabigatran in albumin solution and up to 96% of radiocontrast, creating the premises of a possible all-inclusive method of antiplatelets, anticoagulants, and radiocontrast removal. Conclusion: Sorbent adsorption demonstrates robust removal of ticagrelor from BSA solution and human blood samples.
Use of 18F-FDG PET/CT for the Evaluation of Carcinoma Arising From Choledochal Cysts
Authors: Qiao He, Linqi Zhang, Bing Zhang, Xiangsong Zhang
Journal: Clinical Nuclear Medicine (2018)

Choledochal cysts are rare congenital anomalies of the biliary tree, which are more prevalent in female Asian population. Malignant transformation occurs in 10% to 30% of adults with choledochal cysts. A 39-year-old man presented with abdominal pain for 2 months, with irregular thickening of bile duct wall on ultrasound and enhanced CT. Staging with F-FDG PET/CT demonstrated lymph node and liver metastasis. F-FDG PET/CT may become a valuable imaging procedure in diagnosing and staging of carcinoma arising from choledochal cysts.
Abstract 11389: Presentation Symptoms and Outcomes in Diabetic Patients With Acute Coronary Syndromes: Insights From the Second Gulf Registry of Acute Coronary Events
Authors: Amar M Salam, Khalid AlHabib, Wael Almahmeed, Alawi Alsheikh-Ali, Kadhim Sulaiman, Haitham Amin, Jawad Al-Lawati, Ahmed Al-Motarreb, Nidal Asaad, Rajvir Singh, Jassim Al-Suwaidi
Journal: Circulation (2014)

OBJECTIVES: It is well recognized that cardiac autonomic neuropathy associated with diabetes mellitus (DM) can cause silent myocardial ischemia, however there is limited research examining how the cardiac symptoms reported by patients with DM presenting with acute coronary syndromes (ACS) can affect the immediate and long term outcomes. The aim of the current study was to examine the prognostic impact of lack of chest pain symptoms in DM patients presenting with ACS and enrolled in a multicenter multinational ACS registry from the Middle East. METHODS: For a period of 9 months in 2008 to 2009, 7,930 consecutive patients with ACS were enrolled from 65 hospitals in 6 Middle East countries. A cohort of 3135 patients with DM were selected of whom 2686 (85.7%) presented with chest pain while 449 patients (14.3%) had no chest pain. Clinical features and outcomes were examined and compared among the two groups. RESULTS: Diabetic patients without chest pain were 5 years older and had significantly higher rates of hypertension (76.1% vs. 63.2%), prior myocardial infarction (35.9% vs. 24.3%), chronic kidney disease (CKD) (17.1% vs. 5.9%) and had significantly higher GRACE risk scores (55.3% vs. 21.4%) at presentation compared to patients with chest pain [All P &lt;0.001]. Covariates independently associated with lack of chest pain in DM patients were; higher Killip class on presentation (OR, 6.2 [95%CI, 4.80-7.88]), female gender (OR, 1.50 [95%CI, 1.14-1.96]), CKD (OR, 1.8 [95%CI, 1.27-2.61]), tachycardia (OR, 2.50 [95%CI, 1.94-3.19]) and advanced age (OR, 1.03 [95%CI, 1.02-1.04]), [All P =0.001]. DM patients without chest pain had a significantly higher in-hospital and 1-year mortality rates (11.4% vs. 3.8%, P =0.001, and 25.7% vs. 12.2%, P =0.001, respectively). Lack of chest pain was an independent predictor of in-hospital and one year mortality (OR, 3.05 [95%CI, 2.05-4.54], P =0.001, and OR, 2.0 [95%CI, 1.52-2.75], P =0.001, respectively). CONCLUSIONS: DM patients with ACS presenting without chest pain are at an increased risk of immediate and long term mortality. Understanding the factors associated with atypical presentations of ACS in patients with DM may help in the earlier detection and more appropriate management of these high risk patients.
First report of invasive pulmonary infection by Didymella microchlamydospora and successful treatment with voriconazole
Authors: M. Salehi, E. Zibafar, S. Mahmoudi, S.J. Hashemi, S.M. Gatmiri, M. Gerami Shoar, S.A. Dehghan Manshadi, B. Jahanbin, R. Alizadeh, L. Hosseinpour, P. Ardi, R. Daie Ghazvini
Journal: Clinical Microbiology and Infection (2018)
Improving the protective effects of aFGF for peripheral nerve injury repair using sulfated chitooligosaccharides
Authors: Yanmei Liu, Fenglin Yu, Beibei Zhang, Meng Zhou, Yu Bei, Yifan Zhang, Jianzhong Tang, Yan Yang, Yadong Huang, Qi Xiang, Yueping Zhao, Qian Liang, Yang Liu
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Injury to the peripheral nerves can result in temporary or life-long neuronal dysfunction and subsequent economic or social disability. Acidic fibroblast growth factor (aFGF) promotes the growth and survival of neurons and is a possible treatment for peripheral nerve injury. Yet, the actual therapeutic utility of aFGF is limited by its short half-life and instability in vivo. In the present study, we prepared sulfated chitooligosaccharides (SCOS), which have heparin-like properties, to improve the bioactivity of aFGF. We investigated the protective effects of SCOS with or without aFGF on RSC96 cells exposed to Na2S2O4 hypoxia/reoxygenation injury. Cell viability was measured by MTT assay and cytotoxicity induced by Na2S2O4 was assessed by lactate dehydrogenase (LDH) release into the culture medium. Pretreatment with aFGF and SCOS dramatically decreased LDH release after injury compared to pretreatment with aFGF or SCOS alone. We subsequently prepared an aFGF/SCOS thermo-sensitive hydrogel with poloxamer and examined its effects in vivo. Paw withdrawal thresholds and thermal withdrawal latencies were measured in rats with sciatic nerve injury. Local injection of the aFGF/SCOS hydrogels (aFGF: 40, 80 µg/kg) increased the efficiency of sciatic nerve repair compared to aFGF (80 µg/kg) hydrogel alone. Especially aFGF/SCOS thermo-sensitive hydrogel decreased paw withdrawal thresholds from 117.75 ± 8.38 (g, 4 d) to 65.74 ± 3.39 (g, 10 d), but aFGF alone group were 140.58 ± 27.54 (g, 4 d) to 89.12 ± 5.60 (g, 10 d) (aFGF dose was 80 µg/kg, P < 0.05, n = 8). The thermal withdrawal latencies decreased from 11.61 ± 2.26 (s, 4 d) to 2.37 ±0.67 (s, 10 d). However, aFGF alone group were from 17.69 ± 1.47 (s, 4 d) to 4.65 ± 1.73 (s, 10 d) (P < 0.05, n = 8). Furthermore, the aFGF/SCOS hydrogels also exhibited good biocompatibility in mice. In summary, SCOS improved the protective effects of aFGF in RSC96 cells injured with Na2S2O4 and increased the efficiency of nerve repair and recovery of function in rats with sciatic nerve injury. These findings pave an avenue for the development of novel prophylactic and therapeutic strategies for peripheral nerve injury.
24-Hour Intraocular Pressure Control with Fixed-dose Combination Brinzolamide 1%/Brimonidine 0.2%
Authors: Robert N. Weinreb, Jason Bacharach, Robert D. Fechtner, Malik Y. Kahook, David Wirta, Steve Burmaster, Xiangyi Meng, Douglas A. Hubatsch
Journal: Ophthalmology (2018)

<h3>Purpose</h3> To determine the intraocular pressure (IOP)-lowering effect of fixed-combination brinzolamide 1%/brimonidine 0.2% (BBFC) over a 24-hour period. <h3>Design</h3> Prospective, multicenter, double-masked, parallel-group clinical trial conducted at 16 academic and nonacademic sites in the United States. <h3>Participants</h3> Subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT) aged ≥18 years with mean baseline IOP measurements in at least 1 eye of ≥21 and <28 mmHg. <h3>Methods</h3> Duplicate mean pneumatonometer IOP measurements were collected every 2 hours over a 24-hour period in controlled light conditions in overnight facilities. Daytime (8 am–8 pm) and nocturnal (10 pm–6 am) IOP measurements were collected in a sitting or supine position, respectively. Baseline 24-hour IOP was measured in untreated subjects after a washout (up to 4 weeks) and eligibility phase. After the baseline visit, participants were randomized 1:1 to receive masked BBFC or vehicle, 1 drop 3 times daily (8 am, 3 pm, and 10 pm) for 4 weeks. At week 4, IOP measurements were repeated in both groups under the same conditions. <h3>Main Outcome Measure</h3> Mean change from baseline in 24-hour IOP at week 4. <h3>Results</h3> Of 125 participants randomized, 123 (98%; BBFC, n = 62; vehicle, n = 61) completed the study. No subjects randomized to BBFC discontinued the study. At week 4, BBFC-treated eyes had significantly reduced mean 24-hour IOP vs. vehicle (least squares mean difference [95% confidence interval]: −2.5 [−3.3, −1.7]; <i>P</i> < 0.001); daytime (−3.4 [−4.3, −2.6]; <i>P</i> < 0.001) and nocturnal (−1.2 [−2.3, 0.0]; <i>P</i> = 0.053) reductions were observed. Mean change from baseline was significantly different between BBFC- and vehicle-treated eyes at all daytime points and 3 of 5 nocturnal time points (10 pm, 12 am, and 6 am; secondary end point). The frequency of adverse events was similar between treatment groups; in the BBFC arm, ocular hyperemia, corneal abrasion, and dysgeusia were the most frequently reported, consistent with events described in the drug label. <h3>Conclusions</h3> This large, multicenter study of 24-hour IOP control with BBFC met its primary end point; BBFC demonstrated significantly superior 24-hour IOP-lowering efficacy versus vehicle after 4 weeks of 3-times-daily treatment in subjects with OAG or OHT.
Safety and Efficacy of Durvalumab With or Without Tremelimumab in Patients With PD-L1–Low/Negative Recurrent or Metastatic HNSCC
Authors: Lillian L. Siu, Caroline Even, Ricard Mesía, Eva Remenar, Amaury Daste, Jean-Pierre Delord, Jürgen Krauss, Nabil F. Saba, Lisle Nabell, Neal E. Ready, Irene Braña, Nuria Kotecki, Dan P. Zandberg, Jill Gilbert, Hisham Mehanna, Marcelo Bonomi, Anthony Jarkowski, Giovanni Melillo, Jon M. Armstrong, Sophie Wildsmith, Jérôme Fayette
Journal: JAMA Oncology (2018)

<h3>Importance</h3> Dual blockade of programmed death ligand 1 (PD-L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) may overcome immune checkpoint inhibition. It is unknown whether dual blockade can potentiate antitumor activity without compromising safety in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) and low or no PD-L1 tumor cell expression. <h3>Objective</h3> To assess safety and objective response rate of durvalumab combined with tremelimumab. <h3>Design, Setting, and Participants</h3> The CONDOR study was a phase 2, randomized, open-label study of Durvalumab, Tremelimumab, and Durvalumab in Combination With Tremelimumab in Patients With R/M HNSCC. Eligibility criteria included PD-L1–low/negative disease that had progressed after 1 platinum-containing regimen in the R/M setting. Patients were randomized (N = 267) from April 15, 2015, to March 16, 2016, at 127 sites in North America, Europe, and Asia Pacific. <h3>Interventions</h3> Durvalumab (20 mg/kg every 4 weeks) + tremelimumab (1 mg/kg every 4 weeks) for 4 cycles, followed by durvalumab (10 mg/kg every 2 weeks), or durvalumab (10 mg/kg every 2 weeks) monotherapy, or tremelimumab (10 mg/kg every 4 weeks for 7 doses then every 12 weeks for 2 doses) monotherapy. <h3>Main Outcomes and Measures</h3> Safety and tolerability and efficacy measured by objective response rate. <h3>Results</h3> Among the 267 patients (220 men [82.4%]), median age (range) of patients was 61.0 (23-82) years. Grade 3/4 treatment-related adverse events occurred in 21 patients (15.8%) treated with durvalumab + tremelimumab, 8 (12.3%) treated with durvalumab, and 11 (16.9%) treated with tremelimumab. Grade 3/4 immune-mediated adverse events occurred in 8 patients (6.0%) in the combination arm only. Objective response rate (95% CI) was 7.8% (3.78%-13.79%) in the combination arm (n = 129), 9.2% (3.46%-19.02%) for durvalumab monotherapy (n = 65), and 1.6% (0.04%-8.53%) for tremelimumab monotherapy (n = 63); median overall survival (95% CI) for all patients treated was 7.6 (4.9-10.6), 6.0 (4.0-11.3), and 5.5 (3.9-7.0) months, respectively. <h3>Conclusions and Relevance</h3> In patients with R/M HNSCC and low or no PD-L1 tumor cell expression, all 3 regimens exhibited a manageable toxicity profile. Durvalumab and durvalumab + tremelimumab resulted in clinical benefit, with minimal observed difference between the two. A phase 3 study is under way. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT02319044
Mast cell disorders: From infancy to maturity
Authors: Amy Wilcock, Rajia Bahri, Silvia Bulfone‐Paus, Peter D. Arkwright
Journal: Allergy (2018)

Abstract Mast cells are typically linked to immediate hypersensitivity and anaphylaxis. This review looks beyond this narrow role, focusing on how these cells have evolved and diversified via natural selection promoting serine protease gene duplication, augmenting their innate host defense function against helminths and snake envenomation. Plasticity of mast cell genes has come at a price. Somatic activating mutations in the mast cell growth factor KIT gene cause cutaneous mastocytosis in young children and systemic mastocytosis with a more guarded prognosis in adults who may also harbor other gene mutations with oncogenic potential as they age. Allelic TPSAB1 gene duplication associated with higher basal mast cell tryptase is possibly one of the commonest autosomal dominantly inherited multi‐system diseases affecting the skin, gastrointestinal tract, circulation and musculoskeletal system. Mast cells are also establishing a new‐found importance in severe asthma, and in remodeling of blood vessels in cancer and atherosclerotic vascular disease. Furthermore, recent evidence suggests that mast cells sense changes in oxygen tension, particularly in neonates, and that subsequent degranulation may contribute to common lung, eye, and brain diseases of prematurity classically associated with hypoxic insults. One hundred and forty years since Paul Ehrlich's initial description of “mastzellen,” this review collates and highlights the complex and diverse roles that mast cells play in health and disease.
“Shocking” number of clinical trials are never reported, say MPs
Authors: Nigel Hawkes
Journal: BMJ (2018)

The proportion of clinical trials that do not publish any results is “shocking,” says a new report from an influential parliamentary committee.

Norman Lamb, a former health minister and now chair of the House of Commons Science and Technology Committee, said, “An astonishing amount of information from clinical trials is going unreported. Many of these are funded with public money, and the taxpayer has a right to expect those who benefit from public funding to follow the rules and publish in full.”

The committee heard evidence that around 50% of trials did not publish any results and that academic researchers were less likely than those working in the pharmaceutical industry to publish. It also found that the Health Research Authority, despite having the promotion of research transparency in the UK as a statutory objective since 2014, had not brought about significant change.

In the report of its findings the committee …
FRI0582 Change in muscle volume and muscle fat fraction as potential non-invasive biomarkers of disease progression: machine learning framework for quantitative analysis of mri data
Authors: D. Fischer, P. Hafner, S. Schmidt, M. Hinton, J. Gonzalez, O. Kubassova
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Change in muscle volume and muscle fat fraction are potential non-invasive biomarkers of disease progression in a number of diseases, including sporadic inclusion body myositis<sup>1</sup> and osteoarthritis<sup>2</sup>. Their measurement from magnetic resonance images (MRI) usually involves time consuming manual segmentations of the images by trained readers, which limits the use of these biomarkers in clinical research and practise. <h3>Objectives</h3> In this study, we present a novel unsupervised k-means-classifier based image processing framework, developed for machine learning approach to segmentation of thigh muscles from MRI and the subsequent calculation of fat fraction from Dixon images. Further, we present validation of the new approach against manual segmentation using longitudinal retrospectively acquired data. <h3>Methods</h3> Axial MR images from the upper thighs including in-phase and out of phase sequences were recorded in a group of 8 subjects at baseline and at a follow up. The 16 imaging time points were manually segmented by an expert reader, who delineated the muscle. For these regions the mean fat fraction was calculated from the in-phase and out of phase Dixon images. The fully automated segmentation was then run on the same images and the resulting fat fractions compared with the manual results. The proposed k-means approach classifies each image pixel according to signal intensity and creates image masks for bone, muscle and fat in three dimensions. The pixel counts from bone, muscle and fat are automatically measured to produce the volume and mean fat fraction. <h3>Results</h3> We compared the mean fat fraction for the two approaches and found linear correlation was good (R<sup>2</sup>=0.9396). Manual segmentations typically took 40 min or more to execute, compared to the automated segmentations, which required less than 5 min on a standard desktop computer <h3>Conclusions</h3> In the present study, we reported a segmentation framework based on unsupervised k-means to measure muscle volume and fat fraction. It offers time savings versus manual segmentations and correlates well with fat fraction measurements. This could be useful for muscle quantification in the fields of osteoarthritis, sports medicine and rehabilitation. Further studies are planned to compare sensitivity of automatically acquired measures to clinical progression. <h3>Acknowledgements</h3> 1. Amato AA et al. Neurology. 2014 83( 24:2239–46. 2. Beattie, K., Davison, M.J., Noseworthy, M. et al. Rheumatol Int (2016) 36: 855. https://doi.org/10.1007/s00296-016-3455-x <h3>Disclosure of Interest</h3> None declared
A phase II trial of prolonged, continuous infusion of low-dose gemcitabine plus cisplatin in patients with advanced malignant pleural mesothelioma.
Authors: Oscar Rodriguez, Diego López, Victor Osvaldo Mendoza-Garcia, Ludwing Alexander Bacon Fonseca, Wendy Muñoz-Montaño, Omar Macedo, Sae Muñiz-Hernandez, Monika Blake, Jose F Corona, Jaime G. De La Garza
Journal: Journal of Clinical Oncology (2014)

7579 Background: Low-dose, prolonged infusion of gemcitabine has effects similar to standard doses in several cancers. We evaluated the toxicity and efficacy of low-dose gemcitabine in prolonged infusion plus cisplatin in patients with advanced pleural mesothelioma. Methods: Patients with mesothelioma received gemcitabine (250 mg/m2) in a 6-h infusion plus cisplatin (35 mg/m2) on days 1 and 8 every three weeks. We used the modified Response Evaluation Criteria In Solid Tumors. This study is registered in Clinical Trials (NCT01869023). Results: We included 44 patients; 82.1% were low risk according to the European Organisation for Research and Treatment of Cancer prognostic group. 39 patients had an objective evaluable response; partial response was observed in 53.8% (21/39), stable disease in 33.3% (13/39) and progression in 12.8% (5/39). The median progression free survival was 6.9 months (95% IC 3.2-10.6 months) and the associated factors were the EORTC risk and histology. The median overall survival was 20.7 months (95% IC 10.7-30.8 months). The functional, physical and emotional roles and dyspnoea, insomnia and pain symptom scales improved. The most commonly graded 3/4 side effects were neutropenia (24.4%), lymphopenia (14.6%), thrombocytopenia (14.7%) and anaemia (12.2%). Conclusions: Low-dose, prolonged gemcitabine infusion plus cisplatin has acceptable toxicity and high efficacy with improved quality of life, representing an affordable regimen for the low-income population. Clinical trial information: NCT01869023.Efficacy data. Best tumor response n = 39* % Complete response 0 0 Partial response 21 53.8 Stable disease 13 33.3 Progression 5 12.8 Global response 21 53.8 Disease control rate (CR + PR + SD) 34 87.1 Abbreviations: CR, complete response; PR, partial response; SD, stable disease. *39/44 patients with objective evaluable response.
Abstract 11589: Myocardial Fibrosis is Associated with Heart Failure in Hypertensive Patients: Assessment with Cardiac Magnetic Resonance and Biomarkers of Collagen Turnover
Authors: Yusuke Nakagawa, Yoshizumi Takei, Michio Imai, Megumi Kunishige, Akiko Matsuo, Minoru Ichikawa, Akira Nishibe, Yoshiyuki Kijima
Journal: Circulation (2011)

Background: The pathophysiology of heart failure (HF) with preserved ejection fraction is poorly understood. One possible mechanism is an active fibrotic process that produced increased ventricular...
Abstract 19616: M3-RNA Encapsulation Technology Enables Rapid and Temporally Restricted Protein Expression
Authors: Raman D Singh, Tyra A Witt, Christopher Livia, Matthew L Hillestad, Vandana M Dhivya, Ruben J Crespo-diaz, Paul G Stalboerger, Andre Terzic, Atta Behfar
Journal: Circulation (2016)

Introduction: Targeted induction of protein synthesis by exogenous delivery of coding synthetic mRNA would provide a unique new resource for intervention. Here, an M3-RNA (Microencapsulated Modifie...
Abstract 14636: The Effect of Enhanced External Counter Pulsation in Blood Lipid Profile in Patients With Coronary Artery Disease
Authors: Ramasamy Subramanian, Himanshu Padh, Sivakadakham N, Pradeep G Nayar
Journal: Circulation (2016)

Introduction: Enhanced External Counter pulsation is a non invasive treatment option for patients with coronary artery disease. The treatment works by stimulating the exercise training effect in pe...
Rectal Indomethacin and Spraying of Duodenal Papilla With Epinephrine Increases Risk of Pancreatitis Following Endoscopic Retrograde Cholangiopancreatography
Authors: Hui Luo, Xiangping Wang, Rongchun Zhang, Shuhui Liang, Xiaoyu Kang, Xiaofeng Zhang, Qifeng Lou, Kangwei Xiong, Jing Yang, Lijuan Si, Wenming Liu, Yunpeng Liu, Yi Zhou, Suli Wang, Mei Yang, Wei Chen, Yanzhi Han, Guochen Shang, Xiaocui Yang, Yongfeng He, Qiang Zou, Wenwei Guo, Yichen Dai, Wei Zeng, Xiaosan Zhu, Rongqing Gong, Xun Li, Zhanguo Nie, Qi Wang, Ling Wang, Yanglin Pan, Xuegang Guo, Daiming Fan
Journal: Clinical Gastroenterology and Hepatology (2018)