tbuckley/cabot-search huggingface dataset:
Abstract 17070: Efficacy and Safety of Alirocumab: Pooled Analyses of 1048 Individuals With Diabetes Mellitus From Five Placebo-controlled Phase 3 Studies of at Least 52 Weeks Duration
Authors: Henry N Ginsberg, Michel Farnier, Jennifer G Robinson, Christopher P Cannon, Naveed Sattar, Marie T Baccara-Dinet, Christelle Lorenzato, Maja Bujas-Bobanovic, Michael J Louie, Helen M Colhoun
Journal: Circulation (2015)

Background: Individuals with diabetes (DM) are at high risk for CVD and may not achieve adequate control of LDL-C levels with current lipid-lowering therapies. Aim: To assess alirocumab (ALI) efficacy and safety in individuals with and without baseline DM. Methods: Five placebo (PBO)-controlled Phase 3 studies of 52-78 weeks were analyzed, comprising 1048 individuals with DM at study entry and 2444 with no DM (safety population). All individuals had hypercholesterolemia, and were on maximally tolerated background statin therapy. Efficacy data were pooled by initial ALI dose; 3 studies (n=1043, ITT analysis) used PBO or ALI 75 mg every 2 weeks (Q2W), increasing to 150 mg Q2W at W12 if LDL-C at W8 ≥ 70 mg/dL; 2 studies (n=2416, ITT analysis) initiated treatment with PBO or ALI 150 mg Q2W. All doses were 1 mL SC injection. Safety data were pooled for all 5 studies. Efficacy data are reported to W24, safety for ≥52 weeks. Results: Individuals with DM had lower mean baseline LDL-C levels. At W12, ALI 75 mg Q2W significantly reduced LDL-C levels from baseline vs PBO with treatment effect consistent regardless of DM status (Table). A higher proportion of participants with no DM received a dose increase at W12, leading to a greater magnitude of reduction at W24 in that group. For those initiating at ALI 150 mg Q2W, LDL-C reductions of 58.3% (DM) and 62.3% (no DM) vs PBO were achieved at W24 (Table). Improvements were seen in other parameters, including TGs, HDL-C, and Lp(a), largely irrespective of baseline DM status. Adverse event (AE) rates were generally comparable in both groups. AEs occurring in ≥5% of individuals in all subgroups were nasopharyngitis and URI. Injection site reactions (ISRs) were less frequent in those with DM: ALI 3.6% and PBO 2.8%, vs no DM: ALI 8.4% and PBO 6.1%. Conclusions: ALI demonstrated robust LDL-C reductions in individuals with and without DM. Safety observations were generally similar regardless of DM status, although those with DM reported fewer ISRs than those without.
Government will give equal weight to mental health in 1.6 million disability benefit reviews
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The UK government has accepted that it will need to review 1.6 million disability benefit claims, after dropping its challenge against a court ruling that found that its proposed changes to payments discriminated against people with mental health conditions.

Last year ministers altered the way that personal independence payments (PIPs) were paid, to exclude people who cited mental health as a reason for claiming a higher rate of the benefit. But in December 2017 the High Court over-ruled the move on the grounds that …
Abstract 20523: Immune Responsive Gene 1-Itaconate Induces Mitochondrial Dysfunction to Impair Ischemic Muscle Revascularization and Perfusion Recovery
Authors: Vijay C Ganta, Min Choi
Journal: Circulation (2017)

Introduction: IRG1 processes citrate to itaconate in mitochondrial Krebs cycle. We have recently shown that IRG1 expression inversely correlates with perfusion recovery in preclinical PAD model (hi...
Development and validation of a gene expression-based signature to predict distant metastasis in locoregionally advanced nasopharyngeal carcinoma: a retrospective, multicentre, cohort study
Authors: Xin-Ran Tang, Ying-Qin Li, Shao-Bo Liang, Wei Jiang, Fang Liu, Wen-Xiu Ge, Ling-Long Tang, Yan-Ping Mao, Qing-Mei He, Xiao-Jing Yang, Yuan Zhang, Xin Wen, Jian Zhang, Ya-Qin Wang, Pan-Pan Zhang, Ying Sun, Jing-Ping Yun, Jing Zeng, Li Li, Li-Zhi Liu, Na Liu, Jun Ma
Journal: The Lancet Oncology (2018)
Abstract 18588: Clinical Impact of New-Generation Atrial Antitachycardia Pacing on Termination of Atrial Tachyarrhytmias in Patients With Bradycardia After Cardiac Surgery
Authors: Shozo Konishi, Hitoshi Minamiguchi, Ozu Kentaro, Hiroya Mizuno, Tomohito Ohtani, Osamu Yamaguchi, Yasushi Sakata
Journal: Circulation (2016)

Introduction: Symptomatic bradycardia and paroxysmal atrial tachyarrhythmias are sometimes clinically problematic in patients after cardiac surgery. Large clinical trial demonstrated that new-gener...
Intrabiliary resection of metastasis originating from colorectal carcinoma during direct peroral cholangioscopy: a new tool for biliary palliation
Authors: Andrea Anderloni, Alessandro Fugazza, Francesco Auriemma, Roberta Maselli, Ferdinando D’Amico, Edoardo Troncone, Alessandro Repici
Journal: Endoscopy (2018)

Intrabiliary growth of a liver metastasis originating from colorectal carcinoma is a rare manifestation of metastatic liver carcinoma, with only a few cases reported in the literature [1] [2] [3]. Radiological characteristics of the "classic" liver metastases are well established, and generally preoperative biopsy to plan a proper surgical strategy is not required. However, the radiological features of intrabiliary liver metastasis may not be distinctive, leading to possible misdiagnosis.
PEPFAR — 15 Years and Counting the Lives Saved
Authors: Anthony S. Fauci, Robert W. Eisinger
Journal: New England Journal of Medicine (2018)

PEPFAR — 15 Years and Counting the Lives Saved Launched in 2003, the President’s Emergency Plan for AIDS Relief has had a major impact on the HIV/AIDS pandemic. Support for the program should continue, allowing it to serve as a model for the control and elimination of other devastating infectious diseases.
Association of Dietary Inflammatory Potential With Colorectal Cancer Risk in Men and Women
Authors: Fred K. Tabung, Li Liu, Weike Wang, Teresa T. Fung, Kana Wu, Stephanie A. Smith-Warner, Yin Cao, Frank B. Hu, Shuji Ogino, Charles S. Fuchs, Edward L. Giovannucci
Journal: JAMA Oncology (2018)

Inflammation is important in colorectal cancer development. Diet modulates inflammation and may thus be a crucial modifiable factor in colorectal cancer prevention.To examine whether proinflammatory diets are associated with increased colorectal cancer risk by using an empirical dietary inflammatory pattern (EDIP) score based on a weighted sum of 18 food groups that characterizes dietary inflammatory potential based on circulating levels of inflammation biomarkers.Cohort study of 46 804 men (Health Professionals Follow-up Study: 1986-2012) and 74 246 women (Nurses' Health Study: 1984-2012) followed for 26 years to examine associations between EDIP scores and colorectal cancer risk using Cox regression. We also examined associations in categories of alcohol intake and body weight. Data analysis began January 17, 2017, and was completed August 9, 2017.EDIP scores calculated from food frequency questionnaires administered every 4 years.Incident colorectal cancer.We documented 2699 incident colorectal cancer cases over 2 571 831 person-years of follow-up. Compared with participants in the lowest EDIP quintile (Q) who had a colorectal cancer incidence rate (per 100 000 person-years) of 113 (men) and 80 (women), those in the highest Q had an incidence rate of 151 (men) and 92 (women), leading to an unadjusted rate difference of 38 and 12 more colorectal cancer cases, respectively, among those consuming highly proinflammatory diets. Comparing participants in the highest vs lowest EDIP Qs in multivariable-adjusted analyses, higher EDIP scores were associated with 44% (men: hazard ratio [HR], 1.44; 95% CI, 1.19-1.74; P < .001 for trend), 22% (women: HR, 1.22; 95% CI, 1.02-1.45; P = .007 for trend), and 32% (men and women: pooled HR, 1.32; 95% CI, 1.12-1.55; P < .001 for trend) higher risk of developing colorectal cancer. In both men and women, associations were observed in all anatomic subsites except for the rectum in women. In subgroups (P ≤ .02 for all interactions), associations differed by alcohol intake level, with stronger associations among men (Q5 vs Q1 HR, 1.62; 95% CI, 1.05-2.49; P = .002 for trend) and women (Q5 vs Q1 HR, 1.33; 95% CI, 0.97-1.81; P = .03 for trend) not consuming alcohol; and by body weight, with stronger associations among overweight/obese men (Q5 vs Q1 HR, 1.48; 95% CI, 1.12-1.94; P = .008 for trend) and lean women (Q5 vs Q1 HR, 1.31; 95% CI, 0.99-1.74; P = .01 for trend).Findings suggest that inflammation is a potential mechanism linking dietary patterns and colorectal cancer development. Interventions to reduce the adverse role of proinflammatory diets may be more effective among overweight/obese men and lean women or men and women who do not consume alcohol.
Abstract 17706: Differentially Expressed Genes in Early and Late Treatment for Occlusive Pulmonary Vasculopathy in Sugen/hypoxia Models: Molecular Basis for Early Treatment
Authors: Yoshihide Mitani, Hirofumi Sawada, Tsutomu Shinohara, Shoichirou Ohtsuki, Noriko Yodoya, Hiroyuki Ohashi, Taichi Kato, Erquan Zhang, Yuhei Nishimura, Toshio Tanaka, Kazuo Maruyama, Masahiro Hirayama
Journal: Circulation (2017)

Introduction: Immature smooth muscle cells and macrophages contribute to the development of occlusive pulmonary vascular disease (PVD) in Sugen/hypoxia-treated (SH) rats, and an endothelin receptor...
Residual adenoma after cold snare polypectomy for small colorectal adenomas: a prospective clinical study
Authors: Daisuke Maruoka, Makoto Arai, Naoki Akizue, Kentaro Ishikawa, Shingo Kasamatsu, Takashi Taida, Hideaki Ishigami, Kenichiro Okimoto, Keiko Saito, Tomoaki Matsumura, Tomoo Nakagawa, Tatsuro Katsuno, Naoya Kato
Journal: Endoscopy (2018)

Abstract Background Endoscopic resection of all colonic adenomas prevents the occurrence of colon cancer and death. The European Society of Gastrointestinal Endoscopy Clinical Guideline recommends resection of all polyps predicted to be adenomas and cold snare polypectomy (CSP) for removal of adenomas ≤ 9 mm on the basis of safety; however, it also states that this recommendation lacks adequate evidence of efficacy. The residual adenoma rate after resection is an important indicator of efficacy, but there have been no reports showing this prospectively. Therefore, we aimed to investigate the residual adenoma rate after CSP of small colonic polyps. Methods Between March 2015 and April 2017, patients who were endoscopically diagnosed with colorectal adenomas &lt; 9 mm underwent CSP, the site being marked with endoscopic clips. Patients with pathologically confirmed adenomas underwent follow-up colonoscopy 3 weeks after CSP and any post-CSP scars were biopsied. The primary endpoint was the presence of pathological residual adenoma 3 weeks after CSP. Results Overall, 126 lesions in 39 patients were removed and 125 (99.2 %) were resected en bloc using CSP. Pathologically, 111 lesions (88.1 %) were confirmed as adenomas (4.2 ± 1.5 mm), with 36 of these (32.4 %) determined to be R0 resections. No complications were observed. All 37 patients with pathologically confirmed adenomas underwent follow-up colonoscopy, and 102 of 111 scars were detected in 33 patients. One pathological residual adenoma (0.98 %, 95 % confidence interval 0.02 % – 5.3 %) was identified. Conclusions CSP appears to be an effective treatment for diminutive and small colorectal adenomas, with a low residual adenoma rate.
Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks
Authors: Theingi Aung, Jim Halsey, Daan Kromhout, Hertzel C. Gerstein, Roberto Marchioli, Luigi Tavazzi, Johanna M. Geleijnse, Bernhard Rauch, Andrew Ness, Pilar Galan, Emily Y. Chew, Jackie Bosch, Rory Collins, Sarah Lewington, Jane Armitage, Robert Clarke
Journal: JAMA Cardiology (2018)

Current guidelines advocate the use of marine-derived omega-3 fatty acids supplements for the prevention of coronary heart disease and major vascular events in people with prior coronary heart disease, but large trials of omega-3 fatty acids have produced conflicting results.
Marked antitumor activity of NK012, 7-ethyl-10-hydroxycamptothecin-incorporating micellar nanoparticle, in liver metastatic tumor model of colorectal cancer
Authors: Takeshi Onda, Eiji Ichimura, Shin-ichi Matsumoto, Kazuya Okamoto, Kiyohiro Nishikawa
Journal: Cancer Research (2007)

1495    Background : NK012 is a micellar-forming nanoparticle of 7-ethyl-10-hydroxycamptothecin (EHC or SN-38), an active metabolite of irinotecan hydrochloride (CPT-11), and gradually releases EHC in enzyme-independent manner at physiological pH. We reported that NK012 maintained high EHC concentrations in tumor tissue for more than 7 days after intravenous administration and exerted superior antitumor activity to CPT-11 against various subcutaneously transplanted solid tumors in rodents (2006 AACR Annual Meeting, #3062). Here, we further evaluated the efficacy of NK012 in liver metastatic model of mouse colon cancer. In addition, the difference of the distribution of NK012 and CPT-11 in metastatic liver tissue was visually demonstrated.   Methods : A suspension of 10 5  cells of Colon 26-L5 (a liver metastatic variant of mouse colon adenocarcinoma Colon 26) was injected via portal vein of anesthetized BALB/c female mice at Day 0. When the metastases were established (Day 5), maximal tolerated dose of NK012 (30 mg/kg/day) or CPT-11 (66.7 mg/kg/day) was administered intravenously by the optimal schedule (q4dx3). On the eighteenth day, liver weight of each mouse was recorded, and growth inhibition of metastatic tumor was estimated. Cell proliferation of liver metastatic tumor was microscopically evaluated by immunohistochemical staining of Ki-67.   Results : NK012 exhibited marked inhibition (96%) of liver metastatic weight of Colon 26-L5, whereas CPT-11 showed moderate growth inhibition (39%). Cell proliferation index of remained region of tumor estimated by Ki-67 immunostaining was much lower in NK012-treated group (26%) than CPT-11-treated (52%) or control group (43%). Distribution of NK012 and CPT-11 in tumor tissue was compared by observing fluorescence of each drug with a fluorescence microscope. Micellar NK012 clearly distributed in tumor tissue and retained for a long period (> 2 days). On the contrary, CPT-11 disappeared rapidly from tumor tissue and could not be detected after 24 hours of administration.   Conclusion : NK012 showed superior antitumor activity to CPT-11 in the liver metastatic tumor model of colon cancer. The improvement of efficacy was accounted for by the sustained exposure time and concentration of EHC released from the micellar NK012, which specifically accumulated in tumor tissue due to leakiness of tumor blood vessel to nano-size molecules. NK012 has potential usefulness for treating patients with liver metastasis of colon cancer. The phase I study of NK012 starts soon in the United States.
Diagnosis and Significance of Pulmonary Microvascular Disease in Diabetes
Authors: Timothy J. Roberts, Andrew T. Burns, Richard J. MacIsaac, Andrew I. MacIsaac, David L. Prior, André La Gerche
Journal: Diabetes Care (2018)

OBJECTIVE To determine whether pulmonary microvascular disease is detectable in subjects with diabetes and associated with diminished exercise capacity using a novel echocardiographic marker quantifying the pulmonary transit of agitated contrast bubbles (PTAC). RESEARCH DESIGN AND METHODS Sixty participants (40 with diabetes and 20 control subjects) performed cardiopulmonary (maximal oxygen consumption [VO2peak]) and semisupine bicycle echocardiography exercise tests within a 1-week period. Pulmonary microvascular disease was assessed using PTAC (the number of bubbles traversing the pulmonary circulation to reach the left ventricle, categorized as low PTAC or high PTAC). Echocardiographic measures of cardiac output, pulmonary artery pressures, and biventricular function were obtained during exercise. RESULTS Subjects with diabetes and control subjects were of similar age (44 ± 13 vs. 43 ± 13 years, P = 0.87) and sex composition (70% vs. 65% male, P = 0.7). At peak exercise, low PTAC was present in more participants with diabetes than control subjects (41% vs. 12.5%, χ2 P = 0.041) and, in particular, in more subjects with diabetes with microvascular complications compared with both those without complications and control subjects (55% vs. 26% vs. 13%, χ2 P = 0.02). When compared with high PTAC, low PTAC was associated with a 24% lower VO2peak (P = 0.006), reduced right ventricular function (P = 0.015), and greater pulmonary artery pressures during exercise (P = 0.02). CONCLUSIONS PTAC is reduced in diabetes, particularly in the presence of microvascular pathology in other vascular beds, suggesting that it may be a meaningful indicator of pulmonary microvascular disease with important consequences for cardiovascular function and exercise capacity.
Association of BTLA upregulation with impaired cytotoxic CD8+ T-cell function and disease progression of patients with hepatocellular carcinoma.
Authors: Junliang Fu, Lin Zhou, Zhixian Hong, Yan Chen, Fu-Sheng Wang
Journal: Journal of Clinical Oncology (2014)

e15117 Background: B- and T-lymphocyte attenuator (BTLA) negatively regulates immune responses; however, it remains unknown the expression profile and functional role of BTLA in patients with hepatocellular carcinoma (HCC). Methods: One-hundred and fifty HCC patients, 33 liver cirrhosis (LC) patients, and 45 healthy individuals were enrolled in the study. Flow cytometry performed to analyze the properties of circulating, tumor- and non-tumor-infiltrating BTLA+ cytotoxic CD8+ T cells in these HCC patients with various stages of disease progression. The Mann-Whitney U test, Kruskal-Wallis H test and Wilcoxon signed ranks test were used to compare groups. Results: We found that BTLA expression was progressively up-regulated on cytotoxic CD8+ T cells in peripheral blood and correlated with disease progression in HCC patients. And tumor-infiltrating cytotoxic CD8+ T cells had higher BTLA expression compared with non-tumor regions. Further analysis revealed that BTLA expression was negatively correlated with granzyme and perforin expression in CD8+ T cells both in peripheral blood and liver. And BTLA+CD8+ T-cell proliferation and degranulation were significantly decreased compared with BTLA-CD8+ T-cell. Importantly, increased BTLA expression on cytotoxic CD8+ T cells were associated with high recurrence rates after HCC resection. Conclusions: These novel findings suggest that BTLA-mediated inhibitory function may play an important role in disease progression of HCC, and represent both a potential prognostic marker and a therapeutic target for the treatment of HCC.
Albumin infusion improves endothelial function in septic shock patients: a pilot study
Authors: Geoffroy Hariri, Jérémie Joffre, Stephanie Deryckere, Naïke Bigé, Guillaume Dumas, Jean-Luc Baudel, Eric Maury, Bertrand Guidet, Hafid Ait-Oufella
Journal: Intensive Care Medicine (2018)
Consultant is jailed for four years for sexual assaults on military recruits
Authors: Clare Dyer
Journal: BMJ (2018)

A former consultant cardiologist and director of medicine at Frimley Park Hospital in Surrey has been jailed for four years for sexual assaults on seven young male military recruits during naked examinations.

Neil Ineson, 62, a former army colonel, was examining the men as part of a contract between Frimley Health NHS Foundation Trust and …
Treat suspected flu with antivirals, hospital doctors are told
Authors: Nigel Hawkes
Journal: BMJ (2018)

Patients admitted to acute hospitals in England with suspected flu should be treated with antiviral drugs as quickly as possible, NHS trusts have been told in a letter from the national medical director, Bruce Keogh.

The value of antivirals such as oseltamivir (Tamiflu) in treating flu is hotly contested—a fact Keogh acknowledges in the letter, noting “divergent views” on how useful they are.

However, given the current strain on services, he writes, “The question arises as to whether antiviral medication could reduce hospital stay, freeing up beds and relieving some of the pressure.” After consulting the chief medical officer and Public Health England, Keogh has decided that the answer …
Abstract 425: Doxorubicin Upregulation of the Fibrotic Transforming Growth Factor-beta Pathway
Authors: Trevi A Ramirez, Greg Aune
Journal: Circulation Research (2016)

Childhood cancer survivors are at an increased risk of heart disease as a result of their cancer treatments. Drugs like doxorubicin (DOX) are an effective part of treatment regimens, but have been proven to cause acute and chronic cardiotoxicity (DOX tox). An under-investigated aspect of DOX tox is the interstitial fibrosis that the majority of patients develop. This project aims to better understand the pathology of DOX-induced cardiac fibrosis and the role of the pro-fibrotic transforming growth factor-beta (TGFb) signaling pathway. Research in the area of fibrosis and the effect of DOX on cardiac fibroblasts will increase our understanding of DOX tox. This understanding will allow for improved treatment of pediatric cancer patients by reducing the cardiotoxic sequelae of many standard chemotherapy regimens. Cardiac fibroblasts, isolated from 3 week old mice and treated with 5 μM DOX, showed an increase in nuclear pSMAD compared to control cells via fluorescent immunocytology (2.06 ± 0.26 vs 1.13 ± 0.15, p&lt;0.05). Mice treated with 3 mg/kg DOX injections from 2 weeks to 6 weeks of age showed increased TGFb staining in the left ventricle (1.83 ± 0.34 vs 0.87 ± 0.28, p&lt;0.05) a week after treatment ceased. A subset of mice were followed into old age and sacrificed at 80 weeks. A clear increase in TGFb was seen with age. However, 80 week mice that were exposed to DOX early in life showed a greater increase in TGFb staining compared to untreated 80 week old mice (44.50 ± 2.48 vs 30.93 ± 2.30, p&lt;0.001). Early DOX exposure causes chronic molecular changes as evidenced by acute and chronic changes in signaling molecules in cardiac tissue. Changes in collagen seen in earlier studies and increases in MMP-2 from the literature suggest a cardiac remodeling phenotype in DOX-exposed animals. This project demonstrates that DOX initiates changes to pro-fibrotic pathways, seemingly driven by the TGFb signaling pathway.
Re: “Comparison of antipseudomonal betalactams for febrile neutropenia empiric therapy: systematic review and network metaanalysis” by Horita et al.
Authors: D. Averbuch, C. Orasch, M. Mikulska, D.M. Livermore, C. Viscoli, I.C. Gyssens, W.V. Kern, G. Klyasova, O. Marchetti, D. Engelhard, M. Akova, T. Calandra, C. Cordonnier
Journal: Clinical Microbiology and Infection (2018)
The T-Cell Receptor Repertoire Predicts Interim-PET in Patients with DLBCL Treated with R-CHOP: An Observational Study from a Prospective Clinical Trial
Authors: Mohamed Shanavas, Mark Hertzberg, Rodney J Hicks, John F Seymour, Joshua W.D. Tobin, Marina Mathews, Santiyagu Francis, Frank Vari, Maher K Gandhi, Colm Keane
Journal: Blood (2017)
Risk of Oral and Upper Gastrointestinal Cancers in Persons With Positive Results From a Fecal Immunochemical Test in a Colorectal Cancer Screening Program
Authors: Manon van der Vlugt, Esmée J. Grobbee, Patrick M. Bossuyt, Amanda C.R.K. Bos, Ernst J. Kuipers, Iris Lansdorp-Vogelaar, Manon C.W. Spaander, Evelien Dekker
Journal: Clinical Gastroenterology and Hepatology (2018)
Managing the Risk of Hepatitis B Virus Reactivation in Patients with B-Cell Lymphomas Treated with Obinutuzumab or Rituximab Immunochemotherapy
Authors: Shigeru Kusumoto, Luca Arcaini, Xiaonan Hong, Jie Jin, Won Seog Kim, Yok Lam Kwong, Marion Peters, Yasuhito Tanaka, Andrew D. Zelenetz, Hiroshi Kuriki, Günter Fingerle-Rowson, Tina Nielsen, Eisuke Ueda, Hanna Piper-Lepoutre, Gila Sellam, Kensei Tobinai
Journal: Blood (2017)