tbuckley/cabot-search huggingface dataset:
Abstract 16353: Triglyceride Reduction With Omega-3 Fatty Acids is Associated With Regression of Coronary Plaque Volume in Subjects With Coronary Artery Disease on Maximal Statin Therapy
Authors: Tarec K Elajami, Abdulhamied Alfaddagh, Francine K Welty
Journal: Circulation (2016)

Introduction: High-dose statin treatment resulted in coronary plaque regression measured by intravascular ultrasound. The benefit of triglyceride (TG) reduction on plaque regression with maximal st...
Abstract P325: Utilization of Cardiac Rehabilitation in Eligible Medical Cardiac Patients
Authors: Timothy R Larsen, Jedediah McMunn, Salman Gohar, Joseph L Austin
Journal: Circulation (2017)

Introduction: Cardiac rehabilitation (CR) is recommended for patients who suffer an acute coronary syndrome (STEMI, non-STEMI, or unstable angina), stable angina, or who receive a percutaneous coronary intervention (PCI). CR reduces both all-cause and cardiovascular mortality and reduces hospitalizations. Despite these benefits the rate of participation among eligible patients in the United States is low- estimated around 20%. Our aim is to identify the rate of participation among our patients, identify patient subsets with low levels of participation, and to identify and remove barriers to participation. Methods: We performed a review of all patients treated at a tertiary care hospital from February 2014 to January 2015 with a condition that qualifies for CR based on current ACC/AHA guidelines. We excluded patients with a surgical indication. We limited our search to patients residing in zip codes within 40 miles of a CR facility within our hospital system (five centers in southwest Virginia). Patients were considered to have participated in CR if they attended at least 1 session of phase two CR occurring within 1 year of hospitalization. Results: We identified 1910 eligible patients, of these 249 (13%) participated in cardiac rehabilitation. Those who participated in CR tended to be younger (mean age 65 versus 70 years), male (71% versus 59%), and nonsmokers (smoking rate 19% in participants versus 25% in nonparticipants). Those with ACS were most likely to participate (167 of 879 eligible patients, 19%), followed by stable angina (19 of 134, 14%) and PCI (63 of 897, 7%). Conclusion: The benefits of CR are substantial including enhanced quality of life and improved survival. We believe all eligible patients should be encouraged to participate in CR. The next phase of our analysis will include identification and removal of barriers to participation. We are actively educating providers on patient eligibility and the benefits of CR with an emphasis on underrepresented demographics (women, elderly, smokers, after PCI, etc).
Obinutuzumab Versus Rituximab in Combination with ACVBP-14 or CHOP-14 Following a PET-Driven Strategy in Aa-IPI 1-3 DLBCL Patients (< 60 years): Third Planned Interim and Final Analyses of the Gained Trial
Authors: Rene-Olivier Casasnovas, Gilles Andre Salles, Lucie Oberic, Caroline Bodet-Milin, Josette Briere, Franck Morschhauser, Herve Tilly, Vincent Ribrag, Thierry Lamy, Catherine Thieblemont, Herve Maisonneuve, Remy Gressin, Krimo Bouabdallah, Corinne Haioun, Gandhi Damaj, Luc Mathieu Fornecker, Reda Bouabdallah, Pierre Feugier, Richard Delarue, Anna Schmitt, Christophe Bonnet, Guillaume Cartron, Jean-Philippe Jais, Alina Berriolo-Riedinger, Thierry Jo Molina, Emmanuel Itti, Steven Le Gouill
Journal: Blood (2017)
Abstract 11609: Neurological Effects of Proprotein Convertase Subtilisin/kexin Type 9(PCSK9) Inhibitors: Direct and Indirect Comparisons
Authors: Nirav Patel, Rajat Kalra, Anand Venkatraman, Hemant Godara, Garima Arora, NavKaranbir S Bajaj, Pankaj Arora
Journal: Circulation (2016)

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors dramatically reduce low-density lipoprotein (LDL) cholesterol levels which may lead to lower cerebrovascular (CVA) events. However, randomized control trials (RCTs) have reported increased neurocognitive (NC) deficits in patients using PCSK9 inhibitors. Hypothesis: CVA and NC event rates are similar in patients treated with or without PCSK9 inhibitors. Methods: RCTs reporting rates of stroke, transient ischemic attacks (TIAs), and NC deficits in patients using PCSK9 inhibitors were identified. Standard meta-analyses techniques were used to compare these outcomes among patients treated with and without PCSK9 inhibitors. Network meta-analyses (NMA) were also conducted to indirectly compare Evolocumab and Alirocumab on aforementioned outcomes. Results: Seventeen RCTs with 14,516 patients were included. Evolocumab was used in 10 RCTS in 6,403 patients whereas Alirocumab was used in 2,932 patients in 7 RCTs. Ten RCTs with 10,318 patients reported stroke. Fourteen RCTs with 12,578 patients reported NC event rates. Five RCTs with 6,710 patients reported TIAs ( Table ). None of the studies using Alirocumab reported data on TIAs. We did not observe any difference in stroke rate, NC deficits or TIAs among 2 studied groups (RR; 1.22, (95% CI: 0.50-2.96), 0.97 (0.43-2.20), and 0.37 (0.06-2.23)) respectively. We observed no difference in stroke and NC deficits among Evolocumab and Alirocumab with NMA ( Figure ). Conclusions: PCSK9 inhibitors did not render any protection from stroke or TIAs. Furthermore, our pooled analysis does not show any increase in NC deficits as reported in previous studies.
Clinical Impact of Iron Overload on Morbidity in Patients with Sickle Cell Disease
Authors: Anuj Shrestha, Punita Grover, Zaheer Ahmed, Daulath Singh, Simran Arora, Sashidhar Manthravadi, Jill Moormeier, An-lin Cheng, Lejla Music-Aplenc, Sheshadri Madhusudhana
Journal: Blood (2017)
Electronic cigarettes for smoking cessation
Authors: Jamie Hartmann-Boyce, Rachna Begh, Paul Aveyard
Journal: BMJ (2018)

### What you need to know

A 42 year old electrician has tried to stop smoking several times, including with the aid of pharmacotherapy and behavioural support. He asks you about using electronic cigarettes (e-cigarettes). His work partner stopped smoking a year ago and is still using e-cigarettes now. He has heard that e-cigarettes are as damaging as the real things and worries that if he ends up addicted to e-cigarettes he’ll not have gained anything. 

About 60% of current adult smokers in Great Britain have tried electronic cigarettes (e-cigarettes), and 18% are current e-cigarette users.1 In England, over 40% of people who try to stop smoking do so with the aid of e-cigarettes.2 About 52% of current e-cigarettes users are former smokers.1 Some people who stop smoking with an e-cigarette are still using e-cigarettes a year later.1 In this article we look at whether e-cigarettes help people who smoke to cut down and stop smoking, what are the health risks from e-cigarette use, and how these compare with smoking.

### Cigarette and nicotine addiction

Most people who smoke cigarettes are addicted, and the main vehicle of that addiction is nicotine. When stopping smoking, people experience cravings for cigarettes, which drives return to smoking. These cravings for smoking are less intense when nicotine is substituted; thus replacing nicotine from sources other than cigarettes can facilitate achieving abstinence.

Transferring from cigarettes to other nicotine delivery devices, such as nicotine replacement therapy (NRT) or e-cigarettes, can transfer cigarette addiction to nicotine addiction. …
Power Doppler ultrasound diagnosis of papillary thyroid carcinoma
Authors: Kuen-Yuan Chen, Ming-Hsun Wu, Chiung-Nien Chen, Koung-Yi Liaw, Fon-Jou Hsieh, Kun-Ming Chen, King-Jen Chang
Journal: Cancer Research (2006)

433  Introduction: Thyroid cancer accounts for approximately 1% of total cancer cases in developed countries; worldwide, there are about 122,000 new cases per year. Clinically, 4 to 7 percent of adult population has a palpable thyroid nodule and 17% to 27% of cases can be found when examined by sonography. Although the incidence of the thyroid nodules is high, only 1 out of 20 clinically identified nodules is malignant. Several gray scale sonographic characteristics have been suggested to be malignant, including hypoechoigenicity, microcalcification and blurred margin. Although the intranodular vascularity has been published in several studies, the previous studies usually evaluated the vascularity by color Doppler sonography and only by semi-quantitative methods. The evaluation of the tumor microcirculation by Doppler sonography has been used in many tumors and defined as vascularity index (VI). Our power Doppler sonography method provides continuous images and has many advantages over conventional color Doppler sonography methods in studying the vascularity. It is more sensitive and less noisy. Purpose: We evaluated the microcirculation of benign and malignant thyroid tumors by power Doppler ultrasound and quantitatively analyzed the vascularity of the thyroid tumors by a self-developed software. Currently, we want to demonstrate an objective method to study whether the intranodular vascularity of thyroid tumors can be a predictive factor for malignant tumors. Method: We performed power Doppler ultrasonography of thyroid tumors before operation from August 2003 to July 2004. The indication for thyroidectomy includes malignancy, suspicious malignancy, large goiter and follicular neoplasm. Totally, 54 patients were enrolled in this study. There were 26 cases of papillary thyroid carcinoma, 21 cases of benign nodular goiters and 7 cases of follicular adenoma. The paired normal samples from the papillary cases or nodular goiters were evaluated in the same time as the control group. The ultrasound unit we used was power Doppler mode (HDI 3500; Phillips, with a 5-12MHz broad band linear array transducer ). All scanned images were analyzed off line through dicom format and by a self-developed software (Institute of Applied Mechanics, National Taiwan University ). Result and Conclusion: In our study, the power Doppler vascular index (PDV) of papillary thyroid carcinoma was higher than nodular goiter and normal control (PTC=20.1021.07, NG=9.789.23, normal=5.415.74), P
Ixazomib for Chronic Graft-Versus-Host Disease (cGVHD) Prophylaxis in Patients Undergoing Allogeneic Transplantation (alloHCT): Preliminary Results of a Phase I/II Study
Authors: Saurabh Chhabra, Parameswaran Hari, Alexis Visotcky, Nirav N Shah, J. Douglas Rizzo, Wael Saber, Anita D'Souza, Binod Dhakal, Ashish Anshu, Robert Thompson, Timothy S. Fenske, Bronwen E. Shaw, William R. Drobyski, Marcelo C. Pasquini, Mehdi Hamadani
Journal: Blood (2017)
Abstract 12746: A Case of Biopsy-Proven Erdheim-Chester Disease Manifesting With Pan-Aortitis, Coronary Artery Encasement, a Large Pericardial Effusion, Orbital Pseudotumors, and a Right Heart Mass
Authors: Daniel M Blumenthal, Cory Perugino, Brian B Ghoshhajra, Adolph M Hutter
Journal: Circulation (2016)

A 72 year-old woman with a distant history of a cryptogenic right middle cerebral artery stroke presented with three days of fatigue, confusion, and recrudescence of old stroke symptoms. . Head and neck imaging demonstrated a small subarachnoid hemorrhage, orbital pseudotumors, cerebellar lesions, and circumferential thickening of the aortic arch and great vessels. Additional imaging of the chest, abdomen, pelvis, and legs revealed a large pericardial effusion, pan-aortitis, and sclerotic intramedullary lesions in both femurs. An electrocardiogram showed sinus rhythm, RBBB, and low voltage. Pulsus paradoxus was 10 mmHg. Laboratory analysis was notable for elevated serum inflammatory markers. Echocardiogram showed brief right ventricular diastolic inversion and a right atrioventricular groove mass. Diagnostic and therapeutic pericardiocentesis yielded 350cc of serosanguinous fluid, and evaluation for rheumatologic, infectious, and neoplastic etiologies was unremarkable. Cardiac magnetic resonance imaging (MRI) confirmed the presence of a right atrioventricular groove pseudotumor with avid late gadolinium enhancement and non-obstructive fibrotic encasement of the right and left anterior descending coronary arteries. The combination of pan-aortitis, orbital pseudotumors, pericardial effusion, coronary encasement, and right heart pseudotumor raised suspicion for Erdheim-Chester disease. Femoral bone biopsy revealed infiltration by CD68 (+), CD1a (-) histiocytes, confirming this diagnosis. Genetic testing identified a mutation in the gene for B-type RAF Kinase (BRAF) protein. Treatment with vemurafenib, a BRAF inhibitor, was initiated, and the patient’s disease has not progressed in the eighteen months since starting this treatment. Erdheim-Chester disease is a rare systemic illness caused by proliferation of non-Langerhans cell histiocytes. Cardiovascular manifestations—such as those seen in this case—complicate a majority of cases, and are the predominant cause of death. At least 50% of cases have mutations in the BRAF gene. While Erdheim-Chester disease has no known cure, vemurafenib represents a promising new therapy for BRAF mutation (+) cases.
JCAR017 Is a Defined Composition CAR T Cell Product with Product and Process Controls That Deliver Precise Doses of CD4 and CD8 CAR T Cell to Patients with NHL
Authors: Christopher G. Ramsborg, Paul Guptill, Clinton Weber, Brian Christin, Ryan P Larson, Kenneth Lewis, Mary Mallaney, Michael Bowen, Eileen Higham, Tina Albertson
Journal: Blood (2017)
A Phase 1/2 Study of the Oral Novel JAK1 Inhibitor INCB052793 As Monotherapy and in Combination with Standard Therapies in Patients with Advanced Hematologic Malignancies
Authors: Amer M. Zeidan, Rachel J. Cook, Rodolfo Bordoni, Ekaterine Asatiani, Gongfu Zhou, Théa Faivre, Michael Byrne, Michael R. Savona
Journal: Blood (2017)
Self-Reactive B Cells in the Germinal Center Reaction
Authors: Robert Brink, Tri Giang Phan
Journal: Annual Review of Immunology (2018)

Maintenance of immunological self-tolerance requires lymphocytes carrying self-reactive antigen receptors to be selectively prevented from mounting destructive or inflammatory effector responses. Classically, self-tolerance is viewed in terms of the removal, editing, or silencing of B and T cells that have formed self-reactive antigen receptors during their early development. However, B cells activated by foreign antigen can enter germinal centers (GCs), where they further modify their antigen receptor by somatic hypermutation (SHM) of their immunoglobulin genes. The inevitable emergence of activated, self-reactive GC B cells presents a unique challenge to the maintenance of self-tolerance that must be rapidly countered to avoid autoantibody production. Here we discuss current knowledge of the mechanisms that enforce B cell self-tolerance, with particular focus on the control of self-reactive GC B cells. We also consider how self-reactive GC B cells can escape self-tolerance to initiate autoantibody production or instead be redeemed via SHM and used in productive antibody responses.
A novel post-surgical prognostic system for colorectal liver metastases treated by preoperative systemic treatment, using tumoral and non tumoral pathological changes, Ras mutation and immunoscore
Authors: P. Baldin, M. Van Den Eynde, B. Mlecnik, G. Bindea, G. Beniuga, J. Carrasco, C. Hubert, B. Navez, A. Jouret-Mourin, J. Galon, M. Komuta
Journal: Journal of Hepatology (2018)
Abstract 19533: Pro-Inflammatory Biomarkers in Heart Failure With Preserved Ejection Fraction in Stable Versus Acutely Decompensated Patients
Authors: Abraham Abernethy, Sadi Raza, Russell Tracy, Peter VanBuren, Jie-Lena Sun, Steven McNulty, Kevin Anstrom, Martin LeWinter
Journal: Circulation (2016)

Introduction: There is limited information about the pathophysiology of decompensation in heart failure with preserved ejection fraction (HFpEF). One proposed mechanism involves intermittent exacer...
Ki67 Proliferative Index in Carcinoid Tumors Involving Ovary
Authors: Xiaotun Zhang, Andrea Jones, Sarah M. Jenkins, Yajue Huang
Journal: Endocrine Pathology (2018)

Primary ovarian carcinoid tumors are rare neoplasms that constitute less than 0.1% of all ovarian carcinomas. However, carcinoid tumors metastatic to ovaries are more common. Cell proliferative rate is an important factor in the determination of neuroendocrine tumor prognosis. Limited data are available as regards Ki67 proliferation index in predicting the physiological features of carcinoid tumors involving the ovary. Pathology files of Mayo Clinic Rochester (1995-2014) were searched, and clinical information was collected from medical records. All cases were stained with an antibody against Ki67, and digital analysis was performed with digital imaging analysis. A total of 36 cases (median age 64 years, range 33-83 years), including 9 primary (median age 68 years, range 33-73 years) and 27 metastatic carcinoid cases (median age 64 years, range 36-83 years), were investigated in the current study. Seven out of nine (77.8%) primary ovarian carcinoids are associated with mature teratoma. Twenty two metastatic carcinoids (81.5%) were from the GI tract, four (14.8%) from the pancreas, and one (3.7%) from the posterior thorax location. There was significant difference of Ki67 index between primary (median 2.3%, range, 0.6-8.4%) and metastatic carcinoid tumors (median 9.7%, range, 1.3-46.7%) (p = 0.002). The survival time is much shorter among patients with metastatic carcinoid tumor (median survival 5.8 years) comparing to primary ovarian carcinoid tumor (median 14.2 years) (p = 0.0005). A strong association between Ki67 index and patient survival time was identified (Hazard ratio for 1-percentage point increase 1.11, p = 0.001). Comparing to primary ovarian carcinoid tumor, metastatic carcinoid usually exhibits a higher Ki67 index and a worse outcome.
Cost-effectiveness of daratumumab plus lenalidomide plus dexamethasone versus lenalidomide plus dexamethasone for treatment of patients with multiple myeloma who have received at least one prior therapy: An analysis of the Pollux trial
Authors: Eric M Maiese, Christopher N Graham, Emma Hawe, Jean-Gabriel Le Moine, Ivo Abraham, Mekre Senbetta
Journal: Blood (2017)
Patient Data Supports the Rationale of Low Dose Cyclophosphamide to Potentiate the Anti-Myeloma Activity of Daratumumab through Augmentation of Macrophage-Induced ADCP
Authors: Serika Naicker, Athina Rigalou, Cian McEllistrim, Alessandro Natoni, Christopher Chiu, Kate Sasser, Aideen Ryan, Michael O'Dwyer
Journal: Blood (2017)
Targeting Chondroitin Sulfate Glycosaminoglycans to Treat Cardiac Fibrosis in Pathological Remodeling
Authors: Rong-Rong Zhao, Matthew Ackers-Johnson, Justus Stenzig, Chen Chen, Tao Ding, Yue Zhou, Peipei Wang, Shi Ling Ng, Peter Y. Li, Gavin Teo, Pauline M. Rudd, James W. Fawcett, Roger S.Y. Foo
Journal: Circulation (2018)

Heart failure is a leading cause of mortality and morbidity, and the search for novel therapeutic approaches continues. In the monogenic disease mucopolysaccharidosis VI, loss-of-function mutations in arylsulfatase B lead to myocardial accumulation of chondroitin sulfate (CS) glycosaminoglycans, manifesting as myriad cardiac symptoms. Here, we studied changes in myocardial CS in nonmucopolysaccharidosis failing hearts and assessed its generic role in pathological cardiac remodeling. Healthy and diseased human and rat left ventricles were subjected to histological and immunostaining methods to analyze glycosaminoglycan distribution. Glycosaminoglycans were extracted and analyzed for quantitative and compositional changes with Alcian blue assay and liquid chromatography-mass spectrometry. Expression changes in 20 CS-related genes were studied in 3 primary human cardiac cell types and THP-1-derived macrophages under each of 9 in vitro stimulatory conditions. In 2 rat models of pathological remodeling induced by transverse aortic constriction or isoprenaline infusion, recombinant human arylsulfatase B (rhASB), clinically used as enzyme replacement therapy in mucopolysaccharidosis VI, was administered intravenously for 7 or 5 weeks, respectively. Cardiac function, myocardial fibrosis, and inflammation were assessed by echocardiography and histology. CS-interacting molecules were assessed with surface plasmon resonance, and a mechanism of action was verified in vitro. Failing human hearts displayed significant perivascular and interstitial CS accumulation, particularly in regions of intense fibrosis. Relative composition of CS disaccharides remained unchanged. Transforming growth factor-β induced CS upregulation in cardiac fibroblasts. CS accumulation was also observed in both the pressure-overload and the isoprenaline models of pathological remodeling in rats. Early treatment with rhASB in the transverse aortic constriction model and delayed treatment in the isoprenaline model proved rhASB to be effective at preventing cardiac deterioration and augmenting functional recovery. Functional improvement was accompanied by reduced myocardial inflammation and overall fibrosis. Tumor necrosis factor-α was identified as a direct binding partner of CS glycosaminoglycan chains, and rhASB reduced tumor necrosis factor-α-induced inflammatory gene activation in vitro in endothelial cells and macrophages. CS glycosaminoglycans accumulate during cardiac pathological remodeling and mediate myocardial inflammation and fibrosis. rhASB targets CS effectively as a novel therapeutic approach for the treatment of heart failure.
Sagittal orientation and uniform entry for thoracic pedicle screw placement with free-hand technique: A retrospective study on 382 pedicle screws
Authors: H. Bahadir Gokcen, Sinan Erdogan, Sidar Ozturk, Gurkan Gumussuyu, Irem Bayram, Cagatay Ozturk
Journal: International Journal of Surgery (2018)
iRhom2 promotes lupus nephritis through TNF-α and EGFR signaling
Authors: Xiaoping Qing, Yurii Chinenov, Patricia Redecha, Michael Madaio, Joris J.T.H. Roelofs, Gregory Farber, Priya D. Issuree, Laura Donlin, David R. Mcllwain, Tak W. Mak, Carl P. Blobel, Jane E. Salmon
Journal: Journal of Clinical Investigation (2018)

Lupus nephritis (LN) often results in progressive renal dysfunction. The inactive rhomboid 2 (iRhom2) is a newly identified key regulator of A disintegrin and metalloprotease 17 (ADAM17), whose substrates, such as TNF-α and heparin-binding EGF (HB-EGF), have been implicated in the pathogenesis of chronic kidney diseases. Here, we demonstrate that deficiency of iRhom2 protects the lupus-prone Fcgr2b–/– mice from developing severe kidney damage without altering anti-double-stranded DNA (anti-dsDNA) Ab production by simultaneously blocking HB-EGF/EGFR and TNF-α signaling in the kidney tissues. Unbiased transcriptome profiling of kidneys and kidney macrophages revealed that TNF-α and HB-EGF/EGFR signaling pathways are highly upregulated in Fcgr2b–/– mice, alterations that were diminished in the absence of iRhom2. Pharmacological blockade of either TNF-α or EGFR signaling protected Fcgr2b–/– mice from severe renal damage. Finally, kidneys from LN patients showed increased iRhom2 and HB-EGF expression, with interstitial HB-EGF expression significantly associated with chronicity indices. Our data suggest that activation of iRhom2/ADAM17-dependent TNF-α and EGFR signaling plays a crucial role in mediating irreversible kidney damage in LN, thereby uncovering a target for selective and simultaneous dual inhibition of 2 major pathological pathways in the effector arm of the disease.
The Pan-FLT3/BTK Multi-Kinase Inhibitor CG '806 Induces AML Killing in FLT-Mutant and Wild Type Cells, and Exerts Synergistic Pro-Apoptotic Effects with Concomitant Targeting of Anti-Apoptotic Bcl-2 and/or Mcl-1
Authors: Charlie Ly, Weiguo Zhang, Guopan Yu, Hong Mu, Hongying Zhang, William Rice, Michael Andreeff
Journal: Blood (2017)