tbuckley/cabot-search huggingface dataset:
Abstract 19443: Riociguat for the Treatment of Raynaud’s Phenomenon: A Single-dose, Double-blind, Randomised, Placebo-controlled Cross-over Study (DIGIT)
Authors: Michael Huntgeburth, Johannes Kieβling, Gerrit Weimann, Verena Kiepsel, Soundos Saleh, Nicolas Hunzelmann, Stephan Rosenkranz
Journal: Circulation (2015)

Background: Raynaud’s phenomenon (RP) is a digital ischemia caused by vasoconstriction in the digital blood vessels. Triggers of RP include cold and stress. Medical therapy for RP is unsatisfactory, with many patients not responding to treatment. Here we investigated the safety, efficacy and pharmacokinetics of riociguat, a soluble guanylate cyclase stimulator, in patients with RP. Methods: Patients who had primary RP or secondary RP associated with systemic sclerosis (SSc), and a symptom duration of ≥1 year, were randomized to receive a single oral dose of riociguat 2 mg or placebo. Digital blood flow (DBF) in the right index finger was determined by Laser Speckle Contrast Analysis at room temperature (RT) and after 5 minutes of cold water exposure (CWE), both at baseline and 2 hours after study drug administration. Results: In the patients valid for evaluation (n=20), treatment with riociguat led to an increase in DBF versus baseline of 40.6% at RT and 15.1% after CWE. Based on predefined criteria, patients were considered responders if the placebo-corrected DBF after CWE increased by ≥10% versus baseline at 2 hours after drug intake. This was the case in 12/20 (60%) patients. The highest response rates were seen in patients with primary RP and limited cutaneous SSc, whereas patients with RP associated with diffuse cutaneous SSc responded less well. In responders, riociguat led to an increase in DBF versus baseline of 135.7% at RT and 38.9% after CWE. Riociguat Cmax (SD) 2 hours after drug intake was 76 (1.5) μg/ml, which is in the range previously seen in healthy volunteers and patients with pulmonary hypertension. Comparable Cmax values were observed in responders (81 [1.5] μg/ml) and non-responders (71 [1.6] μg/ml). AEs were reported in 5 patients receiving riociguat (headache, n=4; dyspepsia, n=1) and 1 patient receiving placebo (malaise). No serious AEs were reported. Conclusions: In this small pilot study, riociguat was well tolerated in patients with primary and secondary RP, and improved DBF versus placebo in 60% of patients after cold exposure.
Modifiable Risk Factors in Young Adults With First Myocardial Infarction
Authors: Srikanth Yandrapalli, Christopher Nabors, Abhishek Goyal, Wilbert S. Aronow, William H. Frishman
Journal: Journal of the American College of Cardiology (2019)

Modifiable risk factors (RFs) play an important role in the development and prognosis of acute myocardial infarction (AMI).This study sought to study the prevalence rates of modifiable RFs during a first AMI, sex/race differences, and temporal trends in U.S. young adults.This was a retrospective cohort analysis of the U.S. National Inpatient Sample years 2005 and 2015 to identify adults 18 to 59 years of age hospitalized for a first AMI. Prevalence rates, race and sex differences, and temporal trends of hypertension, diabetes mellitus, obesity, smoking, dyslipidemia, and drug abuse were analyzed in these patients.The authors' study included 1,462,168 young adults with a first AMI (mean age 50 ± 7 years, 71.5% men, 58.3% white) of whom 19.2% were 18 to 44 years of age, and 80.8% were 45 to 59 years of age. In the 18- to 44-year group, smoking (56.8%), dyslipidemia (51.7%), and hypertension (49.8%) were most prevalent, and 90.3% of patients had at least 1 RF. In the 45- to 59-year group, hypertension (59.8%), dyslipidemia (57.5%), and smoking (51.9%) were most prevalent, and 92% patients had at least 1 RF. Significant sex and racial disparities were observed in the prevalence of individual RFs. Women had a higher prevalence of diabetes mellitus, hypertension, and obesity, and men had a higher prevalence of dyslipidemia, drug abuse, and smoking. The prevalence of all these RFs increased temporally except for the rate of dyslipidemia, which decreased more recently. Trends were generally consistent across sex and racial groups.During a first AMI in young adults in whom preventive measures are more likely to be effective, modifiable RFs were highly prevalent and progressively increased over time. Significant sex and racial disparities were observed for individual RFs.
Development of a novel cell-based assay to diagnose recurrent focal segmental glomerulosclerosis patients
Authors: Pankaj Srivastava, Ashish K. Solanki, Ehtesham Arif, Bethany J. Wolf, Michael G. Janech, Milos N. Budisavljevic, Sang-Ho Kwon, Deepak Nihalani
Journal: Kidney International (2019)
Reply to: ‘‘Splenic artery aneurysms, portal hypertension and pregnancy”
Authors: Filipe Andrade, Akash Shukla, Christophe Bureau, Marco Senzolo, Louis D'Alteroche, Alexandra Heurgué, Fanny Turon, Juan-Carlos Garcia-Pagan, Frédéric Oberti, Dhiraj Tripathi, Pierre-Emmanuel Rautou
Journal: Journal of Hepatology (2019)
Urinary leukotriene E4 measurement in exercise-induced anaphylaxis provocation test
Authors: Chikako Motomura, Takeshi Oki, Yuki Okamoto, Toshiaki Kawano, Masatoshi Wakatsuki, Koki Okabe, Yuki Okamoto, Takahito Ninomiya, Yuko Akamine, Youko Murakami, Naohiko Taba, Satoshi Honjho, Hiroshi Odajima
Journal: Journal of Allergy and Clinical Immunology (2019)
FOLFIRINOX in pancreatic cancer patients age 75 years or older.
Authors: Jonathan Mizrahi, Jane Rogers, Kenneth R. Hess, Robert A. Wolff, Gauri Rajani Varadhachary, Rachna T. Shroff, Linus Ho, David R. Fogelman, Kanwal Pratap Singh Raghav, Michael J. Overman, Shubham Pant
Journal: Journal of Clinical Oncology (2019)

362 Background: Although FOLFIRINOX (5-Fluorouracil + leucovorin + irinotecan + oxaliplatin) is now the standard of care for patients (pts) with metastatic pancreatic cancer (PC) based on the 2011 study by Conroy et al. which demonstrated improved median overall survival (mOS) (11.1 vs 6.8 months [m] with gemcitabine, P &lt; 0.001), pts &gt; 75 yrs old were excluded from this study. As per SEER 2011-2015 data, 38% of new PC cases are diagnosed in pts age &gt; 75. The purpose of this study was to assess the safety and efficacy of FOLFIRINOX in this group of pts. Methods: We retrospectively analyzed unresectable PC pts, age ≥ 75, treated with FOLFIRINOX at MD Anderson since 2011. Data obtained include demographics, line of treatment (tx), starting dose, progression free survival (PFS), OS and toxicities. Response was determined by chart documentation. Primary outcomes were mOS and rates of grade 3/4 hematologic toxicity (HT). Results: A total of 24 pts (19 male) were included with median age of 76 (range 75 to 84). 18 had metastatic disease, and FOLFIRINOX was the 1st line of tx for 18 of the 24 pts. The median number of cycles administered was 4 (range 1 to 12). The most frequent starting doses of infusional 5-FU, irinotecan and oxaliplatin were 2400, 150 and 75 mg/m 2 , respectively. Bolus 5-FU and leucovorin were omitted in all but 3 pts. Median PFS was 3.7 m (95% CI: 3.0-5.7) with mOS of 11.6 m (95% CI: 6.14-15.7). 16 pts (67%) experienced disease control (response to tx or stable disease). Grade 3 or 4 HT occurred in 11 pts (46%), and 9 (38%) were supported with granulocyte colony-stimulating factor at some point during tx. 6 pts (25%) required hospital admission for any toxicity, most commonly infection (3 pts), and 10 (42%) stopped FOLFIRINOX due to toxicity, most commonly fatigue (6 pts). Conclusions: In this single-center retrospective analysis of 24 unresectable PC pts age 75 or older given FOLFIRINOX, OS outcomes were similar to those reported by Conroy et al in the original trial which excluded pts older than 75. In our review, toxicities including incidences of grade 3 or 4 HT were similar to those reported in the initial study. These data indicate that the use of modified dosing FOLFIRINOX in advanced PC pts older than 75 appears to maintain similar efficacy and toxicity when compared to younger pts.
A Retrospective Analysis of 122 Immune Thrombocytopenia Patients Treated with Dapsone: Efficacy, Safety and Factors Associated with Treatment Response
Authors: Marina Pereira Colella, Elizio Chiacchio Ferraz Alves, Gabriela de França Delmoro, Gabriela G Yamaguti-Hayakawa, Fernanda Andrade Orsi, Erich Vinicius De Paula, Joyce Maria Annichino- Bizzacchi
Journal: Blood (2018)
Health Related Quality of Life and Fatigue in Patients with Pyruvate Kinase Deficiency
Authors: Eduard J. Van Beers, Kevin H. M. Kuo, D. Holmes Morton, Wilma Barcellini, Stefan W. Eber, Bertil Glader, Hassan M. Yaish, Satheesh Chonat, Nina Kollmar, Jenny M. Despotovic, Dagmar Pospisilova, Christine M. Knoll, Janet L. Kwiatkowski, Yves D. Pastore, Alexis A. Thompson, Winfred Wang, Marcin W. Wlodarski, Peter E. Newburger, Yaddanapudi Ravindranath, Jennifer A. Rothman, Heng Wang, Suzanne Holzhauer, Vicky R. Breakey, Madeleine M Verhovsek, Joachim B. Kunz, Sujit Sheth, Mukta Sharma, Melissa J. Rose, Heather A. Bradeen, Melissa A. McNaull, Kathryn Addonizio, David N Williams, Rachael F. Grace
Journal: Blood (2018)
Validation of a Model for Identification of Patients With Compensated Cirrhosis at High Risk of Decompensation
Authors: Indra Neil Guha, Rebecca Harris, Sarah Berhane, Audrey Dillon, Lisa Coffey, Martin W. James, Alessandro Cucchetti, David J. Harman, Guruprasad P. Aithal, Omar Elshaarawy, Imad Waked, Stephen Stewart, Philip J. Johnson
Journal: Clinical Gastroenterology and Hepatology (2019)
Abstract P008: Have Trends in Preventable Hospitalizations Related to Hypertension Decreased Among Elderly Americans? Results From National Inpatient Sample, 2005-2014
Authors: Anshul Saxena, Muni Rubens, Sankalp Das, Lara Arias, Emir Veledar, Khurram Nasir
Journal: Circulation (2018)

Introduction: As number of elderly Americans is projected to double by 2050, population aged ≥65 years will have the highest impact on Medicare spending. The prevalence of elderly population with hypertension (HTN) is around 65% and if patients receive good primary care or an early intervention, these HTN related hospitalizations could be prevented saving millions in Medicare spending. Our objective was to examine the trends in hospitalizations related to HTN and total cost over 10 years among aged ≥65 years. Methods: Using data from Nationwide Inpatient Sample database from 2005-2014, we explored the existence of trends in HTN admission rates and corresponding hospitalization costs among adults ≥65 years vs other age groups. Weighted estimates for rates and mean total cost were reported using SUDAAN after adjusting for complex survey design. Results: Overall, hospitalizations due to HTN increased by 26% in 2014 from 2005. Hospitalizations were highest among patients ≥65 years (57.8%) followed by 40-64 (32.6%) and 18-39 years (9.6%). During 2005-2014, hospitalization rates among ≥65 years increased significantly (10.7%, p &lt;0.001), where as a decreasing trend was observed in other age groups. The total cost of hospitalization significantly increased from $302M in 2005 to $472M in 2014 among ≥65 years ( p &lt;0.001). In general, highest change in total cost was observed among Medicare patients where it increased by 53% to $145 million in 2014 compared to 2005. Conclusion: Hospitalizations and costs associated with HTN, especially Medicare, have increased over the past 10 years among elderly. Although these trends are alarming, these events could be prevented through symptom management at primary care, medication adherence, care coordination, or modifying care-seeking behavior resulting in potential savings of 851M over a year. This would reduce burden of Medicare spending, which is projected to surpass the rate of growth in federal revenues.
A Prospective Observational Study Evaluating Sarcopenia By Using the Bioelectrical Impedance Analysis in Elderly Patients with Hematologic Malignancies
Authors: Takahiro Kamiya, Kota Mizuno, Shinji Ogura, Chisako Ito, Yuriko Fujita, Yoshinobu Aisa, Tomonori Nakazato
Journal: Blood (2018)
The UK DCD Risk Score: Still no consensus on futility in DCD liver transplantation
Authors: Amelia J. Hessheimer, Elisabeth Coll, Patricia Ruíz, Mikel Gastaca, José Ignacio Rivas, Manuel Gómez, Belinda Sánchez, Julio Santoyo, Pablo Ramírez, Pascual Parrilla, Luis Miguel Marín, Miguel Ángel Gómez-Bravo, Juan Carlos García-Valdecasas, Javier López-Monclús, Andrea Boscá, Rafael López-Andújar, Jiliam Fundora-Suárez, Jesús Villar, Álvaro García-Sesma, Carlos Jiménez, Gonzalo Rodríguez-Laíz, Laura Lladó, Juan Carlos Rodríguez, Manuel Barrera, Ramón Charco, Jose Ángel López-Baena, Javier Briceño, Fernando Pardo, Gerardo Blanco, David Pacheco, Beatriz Domínguez-Gil, Víctor Sánchez Turrión, Constantino Fondevila
Journal: Journal of Hepatology (2019)
Prostaglandin E2 Stimulates CREB-Mediated Modification of Histone Variant Nucleosomes at Enhancers to Promote Hematopoietic Stem Cell Fate
Authors: Audrey Sporrij, Eva M. Fast, Brejnev Muhire, Margot Manning, Marian Kalocsay, Robert E. Kingston, Michael Y. Tolstorukov, Leonard I. Zon
Journal: Blood (2018)
Abstract 17583: Autophagy Protects the Heart Against Pressure Overload Induced Heart Failure
Authors: Akihiro Shirakabe, Yoshiyuki Ikeda, Peiyong Zai, Toshiro Saito, Junichi Sadoshima
Journal: Circulation (2015)

Autophagy is an important mechanism for the degradation of cytosolic proteins and organelles. We investigated how autophagy is regulated in the heart in response to pressure overload (PO). Mice were subjected to transverse aortic constriction (TAC) for multiple durations ranging from 1 hour to 30 days. Left ventricular (LV) weight/tibial length (TL) was significantly elevated at Day 5 (6.21 ± 0.10 vs 4.59 ± 0.10, p&lt;0.05) and thereafter. Ejection fraction (EF) was maintained at Day 7 (82.1±3.4 vs 78.4±3.2%), but gradually decreased thereafter (at Day 30, 51.0±4.5, p&lt;0.05). The level of LC3II increased rapidly, peaking at 3 hours (2.4 fold, p&lt;0.05), returned to normal by 24 hours, and then was significantly decreased at Day 5 (-40.0%, p&lt;0.05) and thereafter. Autophagic flux was evaluated with tandem fluorescent LC3. At 6 hours, both GFP/RFP double positive (yellow) dots and RFP dots were significantly increased in the TAC group compared to the sham group, with or without chloroquine (CQ) (yellow 12±2 vs 4±0 CQ(-), 23±3 vs 9±1 CQ(+); RFP 13±2 vs 5±1 CQ(-), 19±1 vs 13±1 CQ(+)). However, both yellow and RFP dots were significantly decreased at Day 7 and thereafter in the TAC group compared to the sham group, with or without CQ. These data suggest that autophagic flux is activated only transiently after TAC, but is inactivated after Day 5. To examine the functional significance of autophagy during PO, beclin1 heterozygous knockout (beclin1-hetKO) mice, atg7 cardiac-specific knockout (Atg7-CKO) mice, and cardiac-specific U6-shRNA beclin1 (U6shRNAbeclin1) mice were subjected to TAC. At Day 7 and 14 of TAC, decreases in EF (60.7 ± 4.8%, 53.8 ± 2.1% and 46.7 ± 5.9%, p&lt;0.05) and increases in lung weight/TL (8.43 ± 0.87, 11.04 ± 4.16 and 18.76 ± 3.77, p&lt;0.05) were exacerbated in beclin1-hetKO, atg7-CKO and U6shRNAbeclin1 mice compared to in control mice. These results suggest that, after transient activation during the initial 24 hours, PO inhibits autophagy below control levels after Day 5, which coincides with the development of cardiac dysfunction. Since heart failure is exacerbated by further suppression of autophagy, autophagy during PO protects the heart from cardiac dysfunction and PO-induced downregulation of autophagy exacerbates heart failure.
Multifunctional polymeric micelle-based chemo-immunotherapy with immune checkpoint blockade for efficient treatment of orthotopic and metastatic breast cancer
Authors: Jiaojie Wei, Yang Long, Rong Guo, Xinlei Liu, Xian Tang, Jingdong Rao, Sheng Yin, Zhirong Zhang, Man Li, Qin He
Journal: Acta Pharmaceutica Sinica B (2019)

Immunotherapy has become a highly promising paradigm for cancer treatment. Herein, a chemo-immunotherapy was developed by encapsulating chemotherapeutic drug doxorubicin (DOX) and Toll-like receptor 7 agonist imiquimod (IMQ) in low molecular weight heparin (LMWH)-d-
Attitudes of consultant physicians to the Calman proposals: a questionnaire survey
Authors: H. M Mather, R. S Elkeles
Journal: BMJ (1995)

To determine the views of a large and representative group of consultant physicians on the Calman proposals, in which acute general medical services will change from being primarily consultant led to consultant provided.Postal questionnaires.All 236 consultant physicians in acute hospitals in North West and South West Thames regions.Replies were received from 179 (76%). One hundred and thirty seven (77%) indicated that they would not resume emergency residential duties, and 126 (71%) indicated that they would probably withdraw from general medical duties under these circumstances. One hundred and twenty six (70%) and 137 (77%) had not inserted a central venous line or temporary pacemaker, respectively, within the previous five years. Of 157 answering a question on the impact of the Calman proposals on the quality of patient services, 125 considered that it would be detrimental, and only 18 (11%) thought that it would be beneficial.Most consultant physicians are not prepared to resume emergency duties and could not do so without retraining in practical procedures. There is widespread antagonism to the Calman proposals, and most physicians consider that their impact on the quality of patient services will be detrimental.
External beam radiotherapy for hepatocellular carcinoma with right atrium tumor thrombus.
Authors: Danielle Sara Bitterman, Samantha K. Edgington, Bridget N. Noe, Daniel W. Kim, Christine E. Eyler, Lipika Goyal, Andrew X. Zhu, Jennifer Yon-Li Wo, Theodore S. Hong
Journal: Journal of Clinical Oncology (2019)

328 Background: Hepatocellular carcinoma (HCC) with right atrium tumor thrombus (RATT) via progression through hepatic veins into the inferior venal cava is a challenging entity with limited treatment options. Given the significant clinical sequelae of RATT, improved locoregional treatments are needed. We examined our experience with palliative right atrium-directed radiotherapy for HCC RATT. Methods: We conducted a retrospective study of 10 patients with HCC RATT treated with radiotherapy between 2011-2018. Patients with localized (n = 5) and metastatic (n = 5) disease were included. Clinical and treatment factors were collected. Results: Median follow-up was 3 mos. Baseline Childs Pugh score was A in 3 patients and B in 7 patients. The table below shows prescription and dosimetric data. No patients experienced grade ≥ 3 toxicity. The only major adverse cardiac event observed after radiotherapy was heart failure in 2 patients, and it was difficult to determine the contribution of treatment versus RATT. Three months post-radiation, 2 patients experienced a Childs Pugh score decline of &gt; 2 points. At last follow-up, 5 patients were deceased, 4 patients were alive without progression, and 1 patient was alive with progression. Median progression free and overall survival was 3 mos (0.5-7 mos) and 3.5 mos (range 0.5-13 mos), respectively. RATT progression occurred in 1 patient, hepatic progression outside the treatment field occurred in 1 patient, and distant progression occurred in 2 patients. Causes of death included RATT progression (n = 1), HCC progression elsewhere (n = 2), hepatic decompensation (n = 1), and aspiration (n = 1). Conclusions: This unique series suggests HCC RATT-directed radiotherapy may be safe and locally effective. Prospective study is needed to understand the optimal treatment of these patients. [Table: see text]
Liver-Resident NK Cells Control Antiviral Activity of Hepatic T Cells via the PD-1-PD-L1 Axis
Authors: Jing Zhou, Hui Peng, Kun Li, Kun Qu, Baohui Wang, Yuzhang Wu, Lilin Ye, Zhongjun Dong, Haiming Wei, Rui Sun, Zhigang Tian
Journal: Immunity (2019)
Abstract 15658: Arginine-vasopressin Levels Are Increased in Heart Failure With Preserved Ejection Fraction and Correlate With LV Hypertrophy
Authors: Julio A Chirinos, Amer Ahmed Syed, Haideliza Soto-Calderon, Izzah Vassim, Swapna Varakantam, Maheswara R Koppula, Scott R Akers, Alexei Y Bagrov, Wen Wei, Edward G Lakatta, Olga Fedorova
Journal: Circulation (2016)

Abstract: Arginine-Vasopressin (AVP) exerts a variety of effects. in addition to its antidiuretic effect via V2 receptors in the kidneys, AVP has vasoconstrictive effects via its action on V1a receptors in the peripheral vasculature. Whether patients with heart failure and preserved ejection fraction (HFpEF) demonstrate increased levels of AVP, and whether this relates to left ventricular remodeling is unknown. Methods: We studied 26 subjects with heart failure and reduced ejection fraction (HFrEF), 28 subjects with HFpEF, and 95 control subjects without heart failure. AVP was measured ELISA (Cayman Chemicals ; USA). In a subgroup of subjects (n=110) we measured LV mass with magnetic resonance imaging (SSFP cine sequences), with LV segmentation using CMR42 (Circle CV Imaging; Calgary, Canada). Results: AVP levels were significantly greater in HFpEF (1.01; 95%CI=0.84 to 1.19)Compared to either HFrEF (0.72; 95%CI=0.58 to 0.87) or controls without HF (0.69; 95%CI=0.62 to 0.75; ANOVA P<0.0001). After adjustme...
Incidence of second and higher order smoking-related primary cancers following lung cancer: a population-based cohort study
Authors: Matthew E Barclay, Georgios Lyratzopoulos, Fiona M Walter, Sarah Jefferies, Michael D Peake, Robert C Rintoul
Journal: Thorax (2019)

Lung cancer 5-year survival has doubled over 15 years. Although the risk of second primary cancer is recognised, quantification over time is lacking. We describe the incidence of second and higher order smoking-related primary cancers in lung cancer survivors, identifying high-incidence groups and how incidence changes over time from first diagnosis.