tbuckley/cabot-search huggingface dataset:
Abstract 13191: Acute Renal Injury and Mortality After Transcatheter Aortic Valve Replacement
Authors: Rafael A Meneguz-Moreno, Antonio D Castro-Filho, Tannas Jatene, Guilherme Barreto G Silva, Mário Barbosa G Nunes, Andreia D Jeronimo, Auristela Isabel d Ramos, Dimytri Siqueira, Alexandre Antonio C Abizaid, Amanda Guerra M Sousa, Jose Eduardo M Sousa
Journal: Circulation (2015)

Introduction: The presence of acute renal injury (AKI) enhances morbimortality after surgical aortic valve. Hypothesis: This prospective observational study aims to determine the incidence of AKI after transcatheter aortic valve replacement (TAVR), its predictors and impact on 30-days and 1-year mortality. Methods: We assessed data from 224 consecutive patients with severe symptomatic aortic stenosis submitted to TAVR between January 2009 and February 2015 on two tertiary cardiologic centers, conducted by the same heart team. All patients used an ionic, low-osmolar, low-viscosity contrast. Kidney injury was defined according to VARC criteria, following AKIN system, and data collected until the seventh day post-procedure. Three patients were excluded due to death during the procedure, considering those deaths not related to renal dysfunction, remaining 221 patients analysed separated in two groups: AKI group and non-AKI group. Follow-up was performed on 30 days and after one year. Results: Fifty two patients (23.5%) developed AKI until seventh day of procedure. Groups 1 and 2 were similar, except for EuroSCORE II (8.66% ± 5.64% vs 7.34% ± 8.58%, p = 0.02) and glomerular filtration rate (GFR) (39.59 ml/min.1.73m2 ± 13.62 vs. 48.49 ± 19.6, p = 0.002). Overall 30 days-mortality and 1-year mortality was 6.3% and 14.0%, respectively. Both 30-day mortality (23.1% vs 1.2%, p &lt; 0.001) and 1-year mortality (44.2% vs 4.7%, p&lt; 0.001) were higher in group 1. In multivariable-adjusted models, the only independent predictor for AKI after TAVR was baseline GFR [hazard ratio (HR) 1.37, CI 95% 1.08-1.77, p = 0.01]. Regarding long term follow-up, AKI (HR 19.86, CI 95% 7.31-53.98, p &lt;0.001) and COPD (HR 3.14, CI 95% 1.05-9.40, p = 0.04) were independent risk factors for 1-year mortality, whilst hypertension (HR 0.269, CI 95% 0.09-0.80, p = 0.01) was shown to be protective for long term mortality. Conclusion: In this TAVR sample, baseline GFR was the only independent predictor of AKI, and patients who developed it had significantly higher mortality at 30 days and 1 year. Acute renal impairment was the strongest risk factor for mortality and adverse cardiovascular events that provided risk information beyond the traditional scores, as EuroSCORE II and STS.
Abstract 15563: Characterization and Prognostic Value of Chromosomal Microarray Findings of Undetermined Significance in Hypoplastic Left Heart Syndrome
Authors: Andrew L Dailey-Schwartz, Mahshid Sababi, Seema Lalani, Shaine A Morris, Hugh Allen, Jeffrey J Kim, Andrew P Landstrom
Journal: Circulation (2017)

Introduction: Chromosomal microarray (CMA) testing for children with hypoplastic left heart syndrome (HLHS) has become common. While CMA-identified known genetic syndromes are often associated with increased mortality, the prognostic significance of variants of unknown significance (VUS) remains unknown. We sought to determine the spectrum, prevalence, and prognostic significance of CMA-associated VUSs in children with HLHS. Hypothesis: VUSs in HLHS are not associated with increased mortality compared to those with no copy number variation detected on CMA. Methods: Neonates with HLHS at our institution that underwent CMA testing prior to staged surgical palliation from June 2008 to December 2016 were reviewed. CMA results were abstracted and genome mapping conducted and compared against ostensibly healthy CNV (DGV genome browser). The primary outcome was death or cardiac transplant. Secondary endpoints were tracheostomy, feeding tube, requiring cardiopulmonary resuscitation or extracorporeal membrane oxyg...
Epigenetically upregulated oncoprotein PLCE1 drives esophageal carcinoma angiogenesis and proliferation via activating the PI-PLCε-NF-κB signaling pathway and VEGF-C/ Bcl-2 expression
Authors: Yunzhao Chen, Dandan Wang, Hao Peng, Xi Chen, Xueping Han, Jie Yu, Wenjie Wang, Lirong Liang, Zheng Liu, Yi Zheng, Jianming Hu, Lan Yang, Jun Li, Hong Zhou, Xiaobin Cui, Feng Li
Journal: Molecular Cancer (2019)

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies. Neovascularization during tumorigenesis supplies oxygen and nutrients to proliferative tumor cells, and serves as a conduit for migration. Targeting oncogenes involved in angiogenesis is needed to treat organ-confined and locally advanced ESCC. Although the phospholipase C epsilon-1 (PLCE1) gene was originally identified as a susceptibility gene for ESCC, how PLCE1 is involved in ESCC is unclear. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used to measure the methylation status of the PLCE1 promoter region. To validate the underlying mechanism for PLCE1 in constitutive activation of the NF-κB signaling pathway, we performed studies using in vitro and in vivo assays and samples from 368 formalin-fixed esophageal cancer tissues and 215 normal tissues with IHC using tissue microarrays and the Cancer Genome Atlas dataset. We report that hypomethylation-associated up-regulation of PLCE1 expression was correlated with tumor angiogenesis and poor prognosis in ESCC cohorts. PLCE1 can activate NF-κB through phosphoinositide-phospholipase C-ε (PI-PLCε) signaling pathway. Furthermore, PLCE1 can bind p65 and IκBα proteins, promoting IκBα-S32 and p65-S536 phosphorylation. Consequently, phosphorylated IκBα promotes nuclear translocation of p50/p65 and p65, as a transcription factor, can bind vascular endothelial growth factor-C and bcl-2 promoters, enhancing angiogenesis and inhibiting apoptosis in vitro. Moreover, xenograft tumors in nude mice proved that PLCE1 can induce angiogenesis, inhibit apoptosis, and increase tumor aggressiveness via the NF-κB signaling pathway in vivo. Our findings not only provide evidence that hypomethylation-induced PLCE1 confers angiogenesis and proliferation in ESCC by activating PI-PLCε-NF-κB signaling pathway and VEGF-C/Bcl-2 expression, but also suggest that modulation of PLCE1 by epigenetic modification or a selective inhibitor may be a promising therapeutic approach for the treatment of ESCC.
Double-Blind, Placebo-Controlled Randomized Trial of Epicutaneous Immunotherapy in Children of Milk-Induced Eosinophilic Esophagitis
Authors: Jonathan M. Spergel, Okan Elci, Amanda Muir, Chris A. Liacouras, Benjamin Wilkins, Deirdre D. Burke, Megan Ott Lewis, Terri F. Brown-Whitehorn, Antonella Cianferoni
Journal: Journal of Allergy and Clinical Immunology (2019)
Legalise and regulate illicit drugs to reduce poverty, say campaigners
Authors: Richard Hurley
Journal: BMJ (2019)

Prohibiting drugs such as heroin, cocaine, and cannabis perpetuates global inequality, the international development organisation Health Poverty Action has said in a new report.

The international development sector has a duty, therefore, to advocate for the urgent reform of punitive policies and for legalised and regulated drug supply markets, it says.

Criminalising low level activity in the drug trade punishes people for being poor, the report claims, while failing to reduce drug supply. Harms could be immediately reduced, it says, by decriminalising all low level activity, including small scale crop growing and trafficking.

“Current drug policies remove any realistic …
Any public health guidelines should always be developed from a consistent, clear evidence base
Authors: Emmanuel Stamatakis, Ding Ding, Mark Hamer, Adrian E Bauman, I-Min Lee, Ulf Ekelund
Journal: British Journal of Sports Medicine (2019)

We thank Chaput and colleagues1 for their comments on our recent review2 that examined the timeliness of sitting guidelines and provided a critical overview of the sedentary behaviour evidence base. To recap for the reader: we argued that evidence of sitting and health is limited and we urged caution to prevent enthusiastic but premature guideline development. Chaput and colleagues argued that the sedentary behaviour evidence base is adequate and that a provisional screen time-based benchmark is better than no benchmark at all. We see four main areas for debate and discuss them in turn.

Initially, our respected international colleagues1 proposed that the field needs to move towards ‘activity mixes’ that take into account the 24-hour compositional nature of the physical activity, sedentary behaviour and sleep data. Consider a weekend day when a person goes for a 3-hour bike ride. That reduces potential sitting time by 3 hours, so these physical activity elements, moderate to vigorous physical activity (MVPA) (bike ride), and sedentary …
Two Randomized Trials of the Effect of Live Attenuated Influenza Vaccine on Pneumococcal Colonization
Authors: Jamie Rylance, Wouter A. A. de Steenhuijsen Piters, Michael J. Mina, Debby Bogaert, Neil French, Daniela M. Ferreira, Jamie Rylance, Wouter A. A. de Steenhuijsen Piters, Sherin Pojar, Elissavet Nikolaou, Esther German, Elena Mitsi, Simon P. Jochems, Beatriz Carniel, Carla Solórzano, Jesús Reiné, Jenna F. Gritzfeld, Mei Ling J. N. Chu, Kayleigh Arp, Angela D. Hyder-Wright, Helen Hill, Caz Hales, Rachel Robinson, Cath Lowe, Hugh Adler, Seher Zaidi, Victoria Connor, Lepa Lazarova, Katherine Piddock, India Wheeler, Emma L. Smith, Ben Morton, John Blakey, Hassan Burhan, Artemis Koukounari, Duolao Wang, Michael J. Mina, Stephen B. Gordon, Debby Bogaert, Neil French, Daniela Ferreira
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

The human nasopharynx is frequently colonized by Streptococcus pneumoniae (the pneumococcus), serving as the reservoir for transmission, a state which necessarily precedes invasive pneumococcal infection. Influenza infection increases pneumococcal colonization density and dysregulates host immune responses, increasing the risk of secondary bacterial pneumonia and death.
Abstract 19398: Interventions to Reduce Sedentary Behavior at Work
Authors: Ariel Bodker, Michael Widlansky, Scott Strath, David Gutterman, Jacquelyn Kulinski
Journal: Circulation (2017)

Introduction: Sedentary behavior is associated with all-cause and CVD morbidity and mortality, independent of physical activity. However, the biological mechanisms underlying the deleterious conseq...
Decrease of Anti-DSG3, but Not Anti-DSG1 Antibody, After Cessation of Sitagliptin Treatment in a Patient With Pemphigus Vulgaris
Authors: Toshiya Handa, Takafumi Kamiya, Yasuyuki Sumikawa, Tomoyuki Minowa, Ayako Kumagai, Masahide Sawada, Hisashi Uhara
Journal: JAMA Dermatology (2019)
Abstract P181: Temporal Relationship Between Changes in Body Weight and Insulin Resistance and Its Impact on Blood Pressure in Response to 2-year Weight-loss Diet Interventions: the POUNDS Lost Trial
Authors: Liyuan Han, Tao Zhang, Dianjianyi Sun, Wenjie Ma, Tiange Wang, Yoriko Heianza, Wei Chen, George A. Bray, Frank M Sacks, Lu Qi
Journal: Circulation (2017)

Introduction: Changes of body weight and insulin resistance (IR) are closely correlated, and their temporal sequences in affecting blood pressure (BP) remain poorly defined. We examined the temporal sequences of weight loss and change of IR, and their relations with blood pressure in the Pounds Lost trial, a randomized weight-loss diet intervention study. Hypothesis: We hypothesized a one-directional temporal relation between weight loss and change of IR in affecting BP during weight-loss diet interventions. Methods: The present study included overweight/obese adults, who were randomized in a 2х2 factorial design to diets containing 20% or 40% fat and 15% or 25% protein (diets with 65%, 55%, 45% and 35% carbohydrate). Weight, IR, systolic and diastolic BP levels were measured at baseline, 6 and 24 months. After excluding the subjects who took antihypertensive or weight-loss drugs, cross-lagged path and mediation analysis were performed among 540 participants. Results: After adjusting for age, race, sex, and diets groups, the cross-lagged path coefficient from baseline weight to 24-month IR (β 1 =0.135, P =0.04) was significantly greater than the path coefficient (β 2 =0.022, P &gt;0.05) from baseline IR to 24-month weight ( P &lt;0.05 for the difference in βs), indicating that weight-loss preceded change of IR. The mediation effects of 24-month IR on the 24-month systolic BP and diastolic BP were estimated at 17.03%( P =0.004) and 20.94% ( P =0.034), respectively. Conclusions: Our dataindicate that weight loss precedes change of IR in affecting changes of BP in response to weight loss diet interventions. Figure 1 . Covariate-adjusted path coefficients from baseline weight to 24-month IR; β 1 and β 2 are cross-lagged path coefficients; r 2 and r 3 are tracking correlations; The difference between β 1 and β 2 was tested using Fisher Z test; * P&lt;0.01, † P&lt;0.05 for difference between β 1 and β 1 .
An open-label, phase II basket study of olaparib and durvalumab (MEDIOLA): Results in patients with relapsed gastric cancer.
Authors: Yung-Jue Bang, Bella Kaufman, Ravit Geva, Salomon M. Stemmer, Sook-Hee Hong, Jong-Seok Lee, Susan M. Domchek, Mark C. Lanasa, Mei Tang, Christopher Gresty, Helen K Angell, Laura L.M. Opincar, Pia Maarit Herbolsheimer, T.R. Jeffry Evans
Journal: Journal of Clinical Oncology (2019)

140 Background: Olaparib is a PARP inhibitor that has shown activity in relapsed gastric cancer (GC) when combined with chemotherapy. MEDIOLA assesses the efficacy and safety of a chemo-free combination of olaparib and durvalumab, an anti-programmed cell death ligand-1 (PD-L1) agent in patients (pts) with solid tumors, including relapsed GC (NCT02734004). Methods: Eligible pts had GC that relapsed following platinum-containing therapy. Pts received olaparib 300 mg PO BID for a 4-wk run-in to allow for serial biopsies, followed by combination olaparib and durvalumab (1.5 g IV q 4 wks) until progressive disease (PD) as measured by RECIST 1.1. Tumor measurements were taken at baseline, 4 wks and q 8 wks thereafter. Primary endpoints were disease control rate (DCR) at 12 wks, safety, and tolerability. The secondary endpoints included DCR at 28 wks, objective response rate (ORR), duration of response (DoR), progression-free survival, and OS. Biomarker endpoints included PD-L1 expression and evaluation of tumor infiltrating lymphocytes. Bayesian predictive probability design was used for statistical analysis. Results: Forty pts were included in the safety and 39 in the efficacy analysis. Among 39 pts, median age was 57 yrs (range 28–77). Nineteen pts (48%) had a grade 3 AE; three pts (8%) a grade 4 AE. Most common AEs were anemia, lipase increase, fatigue, dysphagia, hyponatremia, and alkaline phosphatase increase. Ten pts (25%) had immune-mediated AEs, most commonly rash. The ORR was 10%; two pts had complete response; two had partial response. Median DoR was 11.1 months. DCR at 12 wks was 26%. Further efficacy and biomarker data will be presented. Conclusions: The combination of olaparib and durvalumab was tolerable, with no unexpected AEs. All responses occurred after the addition of durvalumab and were durable, suggesting synergistic treatment effect of the combination in some pts. Furthermore, several pts with early PD showed unexpectedly long survival. DCR at 12 wks was below the target (70%) due to a high rate of early PDs following the olaparib run-in. To address the early treatment failures, an upfront addition of more aggressive therapies to the combination should be explored. Clinical trial information: NCT02734004.
NPM1 Mutated AML Is Characterized By Pre-Leukemic Mutations and the Persistence and Acquisition of Co-Mutations in Molecular Remission Leads to Inferior Prognosis
Authors: Luca Vincenzo Cappelli, Manja Meggendorfer, Constance Baer, Niroshan Nadarajah, Wolfgang Kern, Torsten Haferlach, Claudia Haferlach, Alexander Höllein
Journal: Blood (2018)
Corrigendum to “The effect of enoxacin on osteoclastogenesis and reduction of titanium particle-induced osteolysis via suppression of JNK signaling pathway” [Biomaterials 35 (2014) 5721–5730]
Authors: Xuqiang Liu, Xinhua Qu, Chuanlong Wu, Zanjing Zhai, Bo Tian, Haowei Li, Zhengxiao Ouyang, Xinchen Xu, Wengang Wang, Qiming Fan, Tingting Tang, An Qin, Kerong Dai
Journal: Biomaterials (2019)
Therapeutic targeting of somatostatin receptors in patients with metastatic Merkel cell carcinoma: A retrospective case series.
Authors: Austin Anderson, Jamiluddin Qazi, Erica Shantha, Seesha Takagishi, Jayasri G Iyer, Astrid Blom, Fatemeh Sanaz Behnia, Hubert Vesselle, Paul Nghiem, Shailender Bhatia
Journal: Journal of Clinical Oncology (2015)

e20031 Background: Merkel cell carcinoma (MCC) is an uncommon and aggressive skin cancer with neuroendocrine features. Current therapeutic options for metastatic MCC are suboptimal. Somatostatin receptors (SSTR), usually expressed in most neuroendocrine tumors (NETs), may represent a therapeutic target in MCC tumors. However, there are limited data on the characteristics of SSTR expression and the efficacy of somatostatin analogues (SSA) in metastatic MCC, a high-grade NET. Methods: We performed retrospective analyses on 45 metastatic MCC patients (pts) who had undergone somatostatin receptor scintigraphy (SRS) using In111-pentetreotide. Metastatic MCC pts who were treated with SSA were included in efficacy analysis. Pts were categorized as having a clinical benefit (CB) if the progression-free survival (PFS) was 4 months or longer after initiation of SSAs. Results: The majority (35/45 or 78%) of metastatic MCC pts who underwent SRS had In111-pentetreotide uptake in MCC tumors suggesting expression of SSTR (subtypes 2, 5). 33 of 35 pts received SSA (octreotide-LAR 20-30 mg IM monthly). Therapy was generally well tolerated with no significant treatment-related adverse events. 19 of 33 pts who received SSA had no other concurrent systemic therapy and were evaluable for efficacy analyses. 7 of these 19 pts had at least one target lesion, among which 3 (3 of 7, or 43%) pts had CB with median PFS of 8 months. The other 12 of the 19 pts treated with SSA had received radiation therapy concurrently with SSA and did not have any measurable target lesion; 5 of 12 (42%) pts had CB with a median PFS of 13 months. Characterization of inter-lesional heterogeneity of In111-pentetreotide uptake and of tumor cell SSTR expression by immunohistochemical staining for SSTR-subtypes (1,2,3,4,5), and their correlation with clinical benefit are ongoing. Conclusions: SSTRs are expressed in the majority of metastatic MCC tumors. Carefully selected metastatic MCC patients can benefit from SSA therapy with minimal toxicity. These results suggest SSTRs to be a valid target to pursue for the treatment of metastatic MCC.
Abstract 17138: Eleclazine, a Novel and Selective Late Sodium Current Inhibitor, Suppresses Ventricular Arrhythmias Induced by Acute Global Low-Flow Ischemia
Authors: Xiaoyan Liu, Ping Wang, Shandong Yu, Lin Wu
Journal: Circulation (2017)

Introduction: An increase in late sodium current (INa,L) associated with myocardial ischemia is prone to trigger life-threatening ventricular arrhythmias (VAs). Hypothesis: Eleclazine (GS-6615), a novel and selective INa,L inhibitor, was hypothesized to suppress VAs induced by acute global low-flow ischemia. Methods: Hearts from New Zealand female rabbits were perfused with modified Krebs-Henseleit (K-H) solution in Langendorff mode at a rate of 20 mL/min. Continuous ventricular septal pacing (1HZ) was induced after themo-ablated of the AV nodal. Electrical signals form multiple channel monophasic action potentials (MAP), pseudo 12-lead electrocardiograms and 64-electrode epicardial ventricular mapping were recorded simultaneously. After a minimum of 15min normal perfusion, acute low-flow ischemia was induced by perfusion of 5ml/min. Results: Low-flow ischemia was associated with shortening of epicardial (Epi-) MAPD90 and QT interval from 183±4 and 270±7 ms to 162±4 and 249±6 ms, and prolongation of intra...
Impact of double-flap technique for reconstruction after proximal gastrectomy.
Authors: Kazuki Asanuma, Hirofumi Kawakubo, Shuhei Mayanagi, Rieko Nakamura, Tomoyuki Irino, Kazumasa Fukuda, Norihito Wada, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2019)

134 Background: Proximal gastrectomy (PG) has been performed for proximal early gastric cancer as a minimally invasive procedure. In PG, gastroesophageal reflux disease (GERD) becomes problem, thus several techniques have been reported to reduce GERD. So far, we have mainly performed the method of anastomosis based on double stapling technique (DST) using a trans-oral anvil delivery system for reconstruction after PG. For preventing GERD, we recently introduced double-flap technique (DFT) reported to be more physiological anti-reflux reconstruction which can prevent GERD. So, this study shows superiority of DFT compared to DST. Methods: Patients who have undergone PG for proximal gastric cancer during Jan. 2012 to Jul. 2017 in our hospital were reviewed as candidates. Operation time, blood loss, postoperative anastomotic complication, postoperative hospital stay, postoperative reflux symptom or endoscopic findings, intake of proton pump inhibitor (PPI) at 1 year after the operation, and postoperative nutritional status were retrospectively investigated. Results: DFT was performed in 26 patients whereas DST was performed in 38 patients. Average operation time and postoperative hospital stay was not significant in both groups (DFT group; 275.8±41.4 minutes, 13.6±8.9 days, DST group; 252.2±82.9 minutes, 15.2±7.2 days, respectively). As for postoperative complications higher than Clavien-Dindo Grade III, one case of suture failure was observed in DFT group. Postoperative reflux symptoms and endoscopic findings of gastroesophageal reflux were significantly frequent in DST group compared to DFT group (Reflux symptoms, DFT group : DST group = 0 : 7(p = 0.03), Endoscopic findings, DFT group : DST group = 1 : 11(p &lt; 0.01) , respectively). There were significantly more cases of PPI taking one year after the operation in DST group(DFT group : DST group = 8 : 28 (p &lt; 0.01) ). Average weight loss at one year after the operation and serum level of albumin of in DFT group were 6.0±4.7kg and 4.11±0.29 g/dL, respectively and DST group were 7.6±5.3kg and 3.95±0.39 g/dL, respectively and there were no significance between two groups. Conclusions: DFT is superior to DST as a reconstruction method after PG in terms of suppressing GERD.
First Clinical Experience With 3-Dimensional Echocardiographic Transillumination Rendering
Authors: Davide Genovese, Karima Addetia, Kalie Kebed, Eric Kruse, Megan Yamat, Akhil Narang, Amit R. Patel, Luigi P. Badano, Denisa Muraru, Alexandra Gonçalves, Victor Mor-Avi, Roberto M. Lang
Journal: JACC. Cardiovascular imaging (2019)
Disappearance of Slan-Positive Non-Classical Monocytes As a New Parameter for the Diagnosis of Chronic Myelomonocytic Leukemia with Associated Inflammatory State
Authors: Sihem Tarfi, Bouchra Badaoui, Nicolas Freynet, Margot Morabito, Jeffie Lafosse, Andrea Toma, Pierre Fenaux, Eric Solary, Dorothée Selimoglu-Buet, Orianne Wagner Ballon
Journal: Blood (2018)
Contraception Counseling in Patients With SLE and Other Chronic Medical Conditions Requiring Potentially Teratogenic Medications
Authors: Ann Cameron Barr, Martina L. Badell, Theresa E. Vettese
Journal: JAMA Internal Medicine (2019)

This Teachable Moment emphasizes the importance of contraception counseling in patients with systemic lupus erythematosus and other chronic medical conditions requiring potentially teratogenic medications and outlines the means to overcome the present barriers to such counseling.
Peristomal pyoderma gangrenosum: An exceedingly rare and overdiagnosed entity?
Authors: Stephanie T. Le, Jenny Z. Wang, Claire Alexanian, Samantha Ellis, Yocasta C. Martinez-Alvarado, Stephanie Johng, Apra Sood, Emanual Maverakis
Journal: Journal of the American Academy of Dermatology (2019)