tbuckley/cabot-search huggingface dataset:
Abstract 14764: Left Atrial Appendage Function and Risk of Stroke After Left Atrial Appendage Electrical Isolation in Patients With Long-Standing Persistent AF: Results From the BELIEF Randomized Trial
Authors: Luigi Di Biase, J. David Burkhardt, Prasant Mohanty, Sanghamitra Mohanty, Javier Sanchez, Chintan Trivedi, Mahmut Gunes, Yalçin Gökoglan, Carola Gianni, Rodney Horton, G. Joseph Gallinghouse, Shane Bailey, Jason Zagrodzky, Steven Hao, Richard Hongo, Salwa Beheiry, Pasquale Santangeli, Michela Casella, Antonio Dello Russo, Amin Al-Ahmad, Patrick Hranitzky, Dhanujaya Lakkireddy, Claudio Tondo, Andrea Natale
Journal: Circulation (2015)

Introduction: The Belief Randomized trial sought to assess whether the empirical isolation of the left atrial appendage (LAA) in addition to an extensive ablation could improve success at follow up in patients with long standing persistent (LSP) atrial fibrillation (AF). The aim of this sub-analysis of the trial aimed to evaluate the LAA contraction at the 6 month repeat Trans-esophageal echocardiogram (TEE). Methods: Patients with LSP AF undergoing ablation were enrolled and randomly assigned to undergo empirical LAA isolation along with an extensive ablation or extensive ablation alone. All patients undergoing LAA isolation received a TEE at the 6 months follow up, irrespective of their underlying rhythm. We evaluated TEE parameters and compared thromboembolic complication between groups. Results: We enrolled 173 pts with average age of 63.8 ± 8.5 years and 85.5% male pts. LAA isolation was performed in 101 pts. LAA was not isolated in 72 pts. Follow-up TEE was performed in all pts with LAA isolation. The peak flow velocity in the appendage was low (&lt;0.4 m/s) in 56.4% (57/101) patients. The doppler across the mitral valve demonstrated E-wave to A-wave ratio (E/A) of 2.64 ± 1.4. All patients had E/A &gt;1, out of which 55.4 %( 56/101) had E/A &gt; 2 (p=0.16). One (1.2%) LAA thrombus [Oral anticoagulant warfarin INR subtherapeutic] and 1 (1.2%) LAA smoke [Oral anticoagulant warfarin, INR : 2.24] were detected in the LAA isolation group as an incidental finding at TEE before redo ablation procedure. One patient (0.99%) had stroke in the LAA isolation group after warfarin discontinuation due to a surgical procedure, while 3 (4.2%) stoke/TIA occurred (p=0.31) in the no LAA isolation group (2 pts on warfarin, 1 pt on aspirin). Conclusion: The results of this study show that LAA isolation does not increase the risk of tia/stroke at follow up. This risk appears to be related to the compliance to oral anticoagulation.
A strong adjuvant based on glycol-chitosan-coated lipid-polymer hybrid nanoparticles potentiates mucosal immune responses against the recombinant Chlamydia trachomatis fusion antigen CTH522
Authors: Fabrice Rose, Jeanette Erbo Wern, Francesca Gavins, Peter Andersen, Frank Follmann, Camilla Foged
Journal: Journal of Controlled Release (2017)
Unique strengthening mechanisms of ultrahigh pressure Mg alloys
Authors: Bingcheng Ge, Hui Fu, Kunkun Deng, Qingrui Zhang, Qiuming Peng
Journal: Bioactive Materials (2017)

Ultrahigh pressure technique remarkably extends solid solubility limitation of Al alloying element (∼25 at.%) in Mg alloys, resulting in unique solid-solution strengthening and age hardening response. Microhardness, yield strength and ultimate compressive strength are improved simultaneously without degrading plasticity by forming homogeneous and globular-shaped Mg17Al12 precipitates of 10–30 nm. In addition, thermal resistance is enhanced by eliminating the dominant growth of (101) plane and anchoring dense stacking faults in phase interface.
Abstract 9458: Left Ventricular Deformation Analysis Using Vendor Dependent and Vendor Independent Three-Dimensional Speckle Tracking Software: A Validation Study
Authors: Eriko Shimada, Meihua Zhu, Sumito Kimura, Cole Streiff, Muhammad Ashraf, David J Sahn
Journal: Circulation (2013)

Background: Accurate quantification of myocardial deformation by three dimensional speckle-tracking echocardiography (3DSTE) is useful. A high variability in 3DSTE-derived values has been observed among different ultrasound machines and analysis software. The aim of this study was to compare vendor dependent and vendor independent speckle-tracking software packages using 3D data acquired by the same machine with sonomicrometry as reference method and to elucidate the feasibility of a vendor-independent software. Methods: Ten harvested porcine hearts with 3 sonomicrometry crystals in the endomyocardium of the anterior walls were attached to a pulsatile pump. Hearts are pumped at 5 stroke volumes ranging 30 to 70 ml, with constant rotation and compaction to simulate normal cardiac motion. Echo images were acquired using a Siemens Acuson SC2000. After baseline imaging, glutaraldehyde was injected in the mid-anterior segment simulating myocardial infarction (MI). Images were analyzed using a Siemens analysis package and TomTec Arena program to evaluate the circumferential and longitudinal strain (CS, LS) values in the mid-anterior segment. Results: When comparing strain data obtained by each software systems and sonomicrometry, Pearson correlation coefficients ( R ) of CS and LS determined by the Siemens program were 0.84 and 0.89 (both p&lt;0.05). TomTec Arena produced data with R value of 0.84 and 0.9 (both p&lt;0.05). After simulated MI induction, CS and LS derived from both software systems were significantly decreased and had a good correlation with sonomicrometry with R values ranging from 0.73 to 0.76 (all p&lt;0.05). Conclusions: Both vendor-dependent and independent software systems for 3D speckle-tracking echocardiography showed the ability to accurately detect myocardial deformation.
Association Between Marginal Jawbone Loss and Onset of Rheumatoid Arthritis and Relationship to Plasma Levels of RANKL
Authors: Elin Kindstedt, Linda Johansson, Py Palmqvist, Cecilia Koskinen Holm, Heidi Kokkonen, Ingegerd Johansson, Solbritt Rantapää Dahlqvist, Pernilla Lundberg
Journal: Arthritis & Rheumatology (2017)

To investigate whether periodontitis, characterized by marginal jawbone loss, precedes the onset of symptoms of rheumatoid arthritis (RA), and to analyze plasma levels of RANKL (a cytokine that is crucial for bone resorption) and anti-citrullinated peptide antibodies (ACPAs) in presymptomatic individuals compared with matched referent controls.Marginal jawbone loss was measured on dental radiographs of the premolar/molar regions in the jaws in 176 subjects, 93 of whom subsequently developed RA. Among these participating subjects, 46 had documented radiographs predating symptom onset, and 45 cases could be matched to controls, according to sex, age, and smoking status. Plasma RANKL concentrations were analyzed using enzyme-linked immunosorbent assay. A receiver operating characteristic curve was used to define the cutoff value for RANKL positivity.Bone loss was significantly greater in presymptomatic subjects classified as never smokers compared with that in controls, and increasing levels of bone loss were associated with a higher risk of the subsequent development of RA (hazard ratio 1.03, 95% confidence interval 1.01-1.05). No association between jawbone loss and RA was observed in smokers. A significantly greater extent of marginal jawbone loss was detected in RANKL-positive presymptomatic subjects, and even more pronounced jawbone loss was observed in those who were positive for both RANKL and ACPA.Marginal jawbone loss preceded the clinical onset of RA symptoms, but this was observed only in nonsmokers. Moreover, marginal jawbone loss was significantly greater in RANKL-positive presymptomatic subjects compared with RANKL-negative presymptomatic subjects and was highest in presymptomatic subjects positive for both ACPA and RANKL.
Urine lipoarabinomannan glycan in HIV-negative patients with pulmonary tuberculosis correlates with disease severity
Authors: Luisa Paris, Ruben Magni, Fatima Zaidi, Robyn Araujo, Neal Saini, Michael Harpole, Jorge Coronel, Daniela E. Kirwan, Hannah Steinberg, Robert H. Gilman, Emanuel F. Petricoin, Roberto Nisini, Alessandra Luchini, Lance Liotta
Journal: Science Translational Medicine (2017)

The Mycobacterium tuberculosis –specific antigen lipoarabinomannan measured in the urine of HIV-negative, pulmonary TB-infected patients correlates with disease severity.
Syndecan-1 promotes Wnt/β-catenin signaling in multiple myeloma by presenting Wnts and R-spondins
Authors: Zemin Ren, Harmen van Andel, Wim de Lau, Robin B. Hartholt, Madelon M. Maurice, Hans Clevers, Marie José Kersten, Marcel Spaargaren, Steven T. Pals
Journal: Blood (2017)
Oral Contraceptives and the Small Increased Risk of Breast Cancer
Authors: David J. Hunter
Journal: New England Journal of Medicine (2017)

In this issue of the Journal, Mørch et al.1 present the results of a large prospective study of the association between the use of hormonal contraceptives and the risk of breast cancer among women in Denmark who were younger than 50 years of age. They observed a 20% higher risk among women who were currently using or had recently used hormonal contraceptives than among those who had never used them, and the risk increased with a longer duration of use. The association between the current use of oral contraceptives and breast cancer is well established; the relative risk of 1.20 . . .
The short- and long-term outcomes of pancreatic resection for pancreatic adenocarcinoma in patients older than 75 years.
Authors: Keisuke Kazama, Toru Aoyama, Yosuke Atsumi, Masaaki Murakawa, Manabu Shiozawa, Satoshi Kobayashi, Makoto Ueno, Manabu Morimoto, Norio Yukawa, Takashi Oshima, Takaki Yoshikawa, Yasushi Rino, Munetaka Masuda, Soichiro Morinaga
Journal: Journal of Clinical Oncology (2017)

470 Background: The short- and long-term outcomes of pancreatic resection for pancreatic adenocarcinoma have not been evaluated in elderly patients. Methods: This retrospective study selected patients who underwent curative surgery for pancreatic cancer at our institution. Patients were categorized into two groups; non-elderly patients(age &lt;75 years: group A) and non-elderly patients (age ≥75 years: group B). The surgical morbidity, motality, overall survival (OS), and recurrence-free survival (RFS) rates in the two groups were compared. Results: A total of 221 patients were evaluated in the study. The overall complication rates are 44.8% in Group A and 52.6% in Group B. Surgical mortality was observed in 2 patients due to an abdominal abcess and cardiovascular disease in Group A (1.1%) and in 1 patient due to postoperative bleeding in Group B (2.6%). There were no significant differences (p=0.379 and p=0.456, respectively). Furthermore, the 5-year OS and RFS rates were similar between the elderly patients and non-elderly patients (18.55% vs. 20.2%, p=0.946 and 13.1% vs. 16.0%, p=0.829 respectively). Conclusions: The short-term outcomes and long-term outcomes survival after pancreatic resection for pancreatic adenocarcinoma were almost equal in the elderly and the non-elderly patients in this study. Therefore, it is unnecessary to avoid pancreatic resection for pancreatic adenocarcinoma in elderly patients simply because of their age.
Abstract 16149: Warfarin Use is Associated With Reduced Mortality in Hemodialysis Patients With Atrial Fibrillation
Authors: Brandon Kai, Yuliya Bogorad, Leigh-Anh Nguyen, Su-Jau Yang, Albert Y Shen, Ming-Sum Lee
Journal: Circulation (2016)

Introduction:  The optimal management of stroke prophylaxis in hemodialysis patients with atrial fibrillation is controversial. Studies have yielded conflicting results: some studies have suggested warfarin use is associated with an increased risk of stroke and bleeding, while other studies showed that warfarin use lowers risk of stroke and death.   Methods:  This is a population-based retrospective cohort study of hemodialysis patients with a diagnosis of atrial fibrillation in the Kaiser Permanente Southern California Health System between Jan 1, 2006 to Sept 30, 2015. Patients with at least 7 days of follow-up were grouped into warfarin users and non-warfarin users based on prescription filled for warfarin. We determined the association between warfarin use and the risk of all-cause death, stroke, and bleeding using Cox-proportional hazard models. Survival curves were estimated using the Kaplan-Meier method and analyzed by log-rank test.   Results:  We identified 4286 patients with atrial fibrillation on hemodialysis. Among this group, 989 (23%) patients were prescribed warfarin. When compared to non-warfarin users, patients prescribed warfarin were older, had more congestive heart failure, coronary artery disease, higher CHA2DS2-VASc Score and higher HASBLED score. Warfarin use was associated with lower all-cause death (see figure) (p   Conclusion:  In this cohort of hemodialysis patients with atrial fibrillation, warfarin use is associated with lower all-cause death and ischemic stroke but not with more bleeding complications.
A phase 1, open-label, dose-escalation study of olaratumab as a single agent and in combination with doxorubicin, vincristine/irinotecan, or high-dose ifosfamide in pediatric patients with relapsed or refractory solid tumors.
Authors: Leo Mascarenhas, Datchen Fritz Tai, Michael William Bishop, Steven G. DuBois, Theodore Willis Laetsch, Donna Elise Levy, Sada Pillay
Journal: Journal of Clinical Oncology (2017)

TPS2599 Background: Olaratumab (LY3012207, IMC-3G3), a PDGFRα antagonist, is a targeted human IgG1 monoclonal antibody that specifically binds PDGFRα, blocking PDGF-AA, -BB, and -CC binding and receptor activation. Preclinical studies of olaratumab with or without chemotherapy have demonstrated antitumor activity in human sarcoma xenograft models. Positive survival outcomes were observed in adult patients with advanced soft tissue sarcoma when they were treated with olaratumab + doxorubicin vs doxorubicin alone in a randomized phase 2 trial. Methods: This multicenter clinical trial (NCT02677116) includes patients &lt; 18 years of age with a diagnosis of relapsed or refractory solid tumors not amenable to curative treatment, for whom chemotherapy with doxorubicin, vincristine/irinotecan, or high-dose ifosfamide is deemed appropriate. The primary objective is to determine a recommended dose of olaratumab + ≥1 chemotherapy regimen(s) in pediatric patients based on any dose-limiting toxicity, and olaratumab serum exposure-matching between adult and pediatric patients. Secondary objectives include assessment of antitumor activity of each combination, immunogenicity, and pharmacokinetics. At least 12 pediatric patients will be treated with 1 cycle (21 days) of olaratumab monotherapy (dose level 1 [Part A] and dose level 2 [Part B]) on Days 1 and 8. If the patient does not experience a dose-limiting toxicity in the first cycle of monotherapy, the patient will then receive olaratumab plus either doxorubicin, vincristine/irinotecan, or high-dose ifosfamide per investigator discretion. Dose-limiting toxicity criteria will also be evaluated for the respective combinations in cycle 2. Treatment will continue until disease progression or other discontinuation criteria are met. Dose level 2 will be initiated after acceptable safety results from dose level 1 monotherapy (a minimum of 6 evaluable patients, and the pharmacokinetic profile). As of December 2016, enrollment is currently occurring in dose level 1. Clinical trial information: NCT02677116.
FAM3 gene family: A promising therapeutical target for NAFLD and type 2 diabetes
Authors: Xiaoyan Zhang, Weili Yang, Junpei Wang, Yuhong Meng, Youfei Guan, Jichun Yang
Journal: Metabolism (2017)

Non-alcoholic fatty liver disease (NAFLD) and diabetes are severe public health issues worldwide. The Family with sequence similarity 3 (FAM3) gene family consists of four members designated as FAM3A, FAM3B, FAM3C and FAM3D, respectively. Recently, there had been increasing evidence that FAM3A, FAM3B and FAM3C are important regulators of glucose and lipid metabolism. FAM3A expression is reduced in the livers of diabetic rodents and NAFLD patients. Hepatic FAM3A restoration activates ATP-P2 receptor-Akt and AMPK pathways to attenuate steatosis and hyperglycemia in obese diabetic mice. FAM3C expression is also reduced in the liver under diabetic condition. FAM3C is a new hepatokine that activates HSF1-CaM-Akt pathway and represses mTOR-SREBP1-FAS pathway to suppress hepatic gluconeogenesis and lipogenesis. In contrast, hepatic expression of FAM3B, also called PANDER, is increased under obese state. FAM3B promotes hepatic lipogenesis and gluconeogenesis by repressing Akt and AMPK activities, and activating lipogenic pathway. Under obese state, the imbalance among hepatic FAM3A, FAM3B and FAM3C signaling networks plays important roles in the pathogenesis of NAFLD and type 2 diabetes. This review briefly discussed the latest research progress on the roles and mechanisms of FAM3A, FAM3B and FAM3C in the regulation of hepatic glucose and lipid metabolism.
Nivolumab (nivo) in sorafenib (sor)-naive and -experienced pts with advanced hepatocellular carcinoma (HCC): CheckMate 040 study.
Authors: Todd S. Crocenzi, Anthony B. El-Khoueiry, Thomas Cheung Yau, Ignacio Melero, Bruno Sangro, Masatoshi Kudo, Chiun Hsu, Jorg Trojan, Tae-You Kim, Su-Pin Choo, Tim Meyer, Yoon-Koo Kang, Winnie Yeo, Akhil Chopra, Adyb Baakili, Christine Marie Dela Cruz, Lixin Lang, Jaclyn Neely, Theodore Welling
Journal: Journal of Clinical Oncology (2017)

4013 Background: Many pts with advanced HCC progress on SOC therapy. Nivo is a fully human anti–PD-1 IgG4 mAb that demonstrated durable responses (20% ORR with a median DOR of 9.9 mo; 9-mo OS rate was 74%) in pts with advanced HCC in the dose-expansion (EXP) phase of the CheckMate 040 study (NCT01658878; Melero et al. 2017). Here we present survival and durability of response data in both sor-naive and -experienced pts with advanced HCC in CheckMate 040. Methods: Pts naive to or previously treated with sor received nivo in phase 1/2 dose-escalation (ESC; 0.1–10 mg/kg) and -EXP (3 mg/kg) cohorts Q2W regardless of PD-L1 status. Primary endpoints were safety/tolerability (ESC) and ORR (EXP; ORR by investigator [INV] and blinded independent central review [BICR]) using RECIST v1.1. Secondary endpoints included DOR, DCR, and OS. Biomarkers were assessed using pre-treatment tumor samples. Results: Overall, pts (N=262) had a median follow-up of 12.9 mo, and 98% had Child-Pugh scores 5–6. In sor-naive pts (n=80), the ORR (INV) was 23%, with 44% of responses (8/18) ongoing (Table). The DCR was 63%; 40% of pts had stable disease ≥6 mo. In sor-experienced pts (n=182; 91% progressed on sor), the ORRs (INV) were 16%–19%. Overall, responses occurred regardless of etiology or tumor cell PD-L1 expression. Nivo had a manageable safety profile consistent with that reported in other tumor types. Updated data with additional 4 mo of follow-up will be presented. Conclusions: Nivo demonstrated durable responses with long-term survival and favorable safety in both sor-naive and -experienced pts with advanced HCC. Clinical trial information: NCT01658878. [Table: see text]
Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial
Authors: Michael Wang, Simon Rule, Pier Luigi Zinzani, Andre Goy, Olivier Casasnovas, Stephen D Smith, Gandhi Damaj, Jeanette Doorduijn, Thierry Lamy, Franck Morschhauser, Carlos Panizo, Bijal Shah, Andrew Davies, Richard Eek, Jehan Dupuis, Eric Jacobsen, Arnon P Kater, Steven Le Gouill, Lucie Oberic, Taduesz Robak, Todd Covey, Richa Dua, Ahmed Hamdy, Xin Huang, Raquel Izumi, Priti Patel, Wayne Rothbaum, J Greg Slatter, Wojciech Jurczak
Journal: The Lancet (2017)
Liver fibrosis scores in the general population: Better risk indices are needed!
Authors: Fredrik Åberg
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. TO THE EDITOR: Unalp‐Arida and Ruhl are to be congratulated on their analysis of liver fibrosis scores in predicting liver mortality in the unselected general population.1 With the increasing population burden of liver disease, especially nonalcoholic fatty liver disease (NAFLD), it is a great unmet need to be able to detect individuals in the general population that are at high risk of developing clinical, complicated liver disease, in order to target a more intense diagnostic liver workup, possible specific treatment, and closer follow‐up to these individuals. Liver enzymes or simple steatosis alone are insufficient given that only a small fraction of those with elevated transaminases or steatosis will ever develop clinical liver disease. With the degree of liver fibrosis being the strongest prognostic factor, estimates of liver fibrosis based on readily available laboratory measurements are attractive. Unalp‐Arida and Ruhl1 found increased liver mortality among individuals with high fibrosis risk as estimated by aspartate aminotransferase to platelet ratio index (APRI), NAFLD fibrosis score, Fibrosis‐4 (FIB‐4), and Forns score. However, among subjects deemed to have such high fibrosis risk, the proportion of deaths attributable to liver disease was small: 4% for NAFLD fibrosis score, 7% for FIB‐4, and 19% for APRI (intermediate and high risk combined because of small numbers!). Moreover, the proportion of liver deaths captured by a high fibrosis risk was also quite unsatisfactory: 34% for APRI (intermediate to high), 24% for FIB‐4, and 25% for NAFLD fibrosis score. Taking into account the population prevalence of high fibrosis risk and based on the numbers given in the article, the age‐adjusted population attributable fraction for the various scores is estimated to range from 30% to 40%. This is the proportion of liver deaths in the general population that is attributed to a high fibrosis risk score, as measured in the study. In other words, 60%‐70% of liver deaths are not captured by a high liver fibrosis score. Therefore, none of the scores tested showed sufficient utility to be useful in the unselected general population. Although serial measurements would likely improve the utility of these scores because the study spanned 23 years, an issue also acknowledged by the researchers, there seems to be a need for better risk indices. Such risk indices should ideally incorporate key environmental and genetic drivers of liver disease.2
Missing several GP appointments could be warning sign, say researchers
Authors: Jacqui Wise
Journal: BMJ (2017)

Patients who repeatedly fail to attend GP appointments are likely to be among the most socioeconomically deprived, says new research. The researchers said that missing several appointments could be a warning sign that something major is wrong and that follow-up action is needed.

The three year retrospective study published in the Lancet Public Health examined the appointment histories between 2013 and 2016 of 550 083 patients from 134 general practices in Scotland. It found that nearly half (46%) of patients missed one or more appointment and that 19% missed more …