tbuckley/cabot-search huggingface dataset:
E-cigarettes can help people quit smoking but more evidence needed on long term harms, review concludes
Authors: Jacqui Wise
Journal: BMJ (2020)

An updated Cochrane review has concluded that electronic cigarettes containing nicotine could increase the number of people who successfully stop smoking compared with other approaches such as nicotine gum or patches.1 The review authors did not detect any clear evidence of serious harms from nicotine e-cigarettes but said that more evidence was needed.

In September the Committee on Toxicity of Chemicals in Food, Consumer Products, and the Environment concluded that e-cigarettes were significantly less harmful than smoking but were not risk-free.2 In 2015 a review commissioned by Public Health England, which concluded that e-cigarettes were 95% less harmful than tobacco, led to widespread criticism …
After PCI and short-term DAPT, P2Y12 inhibitors alone vs. ongoing DAPT reduce major bleeding; CV events do not differ
Authors: Francisco Alvarado, Steven Borzak
Journal: Annals of Internal Medicine (2020)

Source Citation Malik AH, Yandrapalli S, Shetty SS, et al. Meta-analysis of dual antiplatelet therapy versus monotherapy with P2Y12 inhibitors in patients after percutaneous coronary intervention. Am J Cardiol. 2020;127:25-9. 32389351
Retraction notice to “Molecular forms of HMGB1 and keratin-18 as mechanistic biomarkers for mode of cell death and prognosis during clinical acetaminophen hepatotoxicity”
Authors: Daniel J. Antoine, Rosalind E. Jenkins, James W. Dear, Dominic P. Williams, Mitchell R. McGill, Matthew R. Sharpe, Darren G. Craig, Kenneth J. Simpson, Hartmut Jaeschke, B. Kevin Park
Journal: Journal of Hepatology (2020)
67P Evaluation of genetic variants in miR-146-a, miR-618, and miR-181b as risk factors of colorectal cancer in Bulgarian patients
Authors: M. Radanova, G.M. Mihaylova, D. Ivanova, O. Tasinov, N. Nazifova-Tasinova, R. Manev, N. Conev, Z. Mihaylova, I. Donev
Journal: Annals of Oncology (2020)
Ocular barriers to retinal delivery of intravitreal liposomes: Impact of vitreoretinal interface
Authors: Shirin Tavakoli, Karen Peynshaert, Tatu Lajunen, Joke Devoldere, Eva M. del Amo, Marika Ruponen, Stefaan C. De Smedt, Katrien Remaut, Arto Urtti
Journal: Journal of Controlled Release (2020)

Drug delivery to the posterior segment of the eye is challenging due to several anatomical and physiological barriers. Thus, there is a need for prolonged action and targeted drug delivery to treat retinal diseases. Intravitreal injections avoid anterior eye barriers, but the vitreoretinal interface and inner limiting membrane (ILM) may prevent access of drug delivery systems to the retina. Existing data on retinal permeation of intravitreal nanoparticles are sparse and probably misleading due to the inter-species differences of retinal structures in rodents and humans. To bridge this gap, retinal permeation of light-activated liposomes was studied in an ex vivo bovine explant system that simulates the structure of vitreoretinal interface and intact ILM. Our findings indicate that the particle size plays a significant role in determining the retinal penetration as the liposomes of >100 nm sized failed to overcome the ILM and could not permeate into the retina. In addition, our results demonstrate the impact of surface charge and PEG-coating on retinal penetration. Small (≈ 50 nm) anionic liposomes with PEG coating showed the most extensive distribution and cellular localization in the retina. In summary, this study extends understanding of ocular barriers, and provides valuable information to augment design of retinal drug delivery systems.
Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment
Authors: Julia López de Andrés, Carmen Griñán-Lisón, Gema Jiménez, Juan Antonio Marchal
Journal: Journal of Hematology & Oncology (2020)

Abstract Cancer stem cells (CSCs) represent a tumor subpopulation responsible for tumor metastasis and resistance to chemo- and radiotherapy, ultimately leading to tumor relapse. As a consequence, the detection and eradication of this cell subpopulation represent a current challenge in oncology medicine. CSC phenotype is dependent on the tumor microenvironment (TME), which involves stem and differentiated tumor cells, as well as different cell types, such as mesenchymal stem cells, endothelial cells, fibroblasts and cells of the immune system, in addition to the extracellular matrix (ECM), different in composition to the ECM in healthy tissues. CSCs regulate multiple cancer hallmarks through the interaction with cells and ECM in their environment by secreting extracellular vesicles including exosomes, and soluble factors such as interleukins, cytokines, growth factors and other metabolites to the TME. Through these factors, CSCs generate and activate their own tumor niche by recruiting stromal cells and modulate angiogenesis, metastasis, resistance to antitumor treatments and their own maintenance by the secretion of different factors such as IL-6, VEGF and TGF-ß. Due to the strong influence of the CSC secretome on disease development, the new antitumor therapies focus on targeting these communication networks to eradicate the tumor and prevent metastasis, tumor relapse and drug resistance. This review summarizes for the first time the main components of the CSC secretome and how they mediate different tumor processes. Lastly, the relevance of the CSC secretome in the development of more precise and personalized antitumor therapies is discussed.
Patient-Reported Social and Behavioral Determinants of Health and Estimated Risk of Hospitalization in High-Risk Veterans Affairs Patients
Authors: Donna M. Zulman, Matthew L. Maciejewski, Janet M. Grubber, Hollis J. Weidenbacher, Dan V. Blalock, Leah L. Zullig, Liberty Greene, Heather E. Whitson, Susan N. Hastings, Valerie A. Smith
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Despite recognition of the association between individual social and behavioral determinants of health (SDH) and patient outcomes, little is known regarding the value of SDH in explaining variation in outcomes for high-risk patients. <h3>Objective</h3> To describe SDH factors among veterans who are at high risk for hospitalization, and to determine whether adding patient-reported SDH measures to electronic health record (EHR) measures improves estimation of 90-day and 180-day all-cause hospital admission. <h3>Design, Setting, and Participants</h3> A survey was mailed between April 16 and June 29, 2018, to a nationally representative sample of 10 000 Veterans Affairs (VA) patients whose 1-year risk of hospitalization or death was in the 75th percentile or higher based on a VA EHR-derived risk score. The survey included multiple SDH measures, such as resilience, social support, health literacy, smoking status, transportation barriers, and recent life stressors. <h3>Main Outcomes and Measures</h3> The EHR-based characteristics of survey respondents and nonrespondents were compared using standardized differences. Estimation of 90-day and 180-day hospital admission risk was assessed for 3 logistic regression models: (1) a base model of all prespecified EHR-based covariates, (2) a restricted model of EHR-based covariates chosen via forward selection based on minimizing Akaike information criterion (AIC), and (3) a model of EHR- and survey-based covariates chosen via forward selection based on AIC minimization. <h3>Results</h3> In total, 4685 individuals (response rate 46.9%) responded to the survey. Respondents were comparable to nonrespondents in most characteristics, but survey respondents were older (eg, &gt;80 years old, 881 [18.8%] vs 800 [15.1%]), comprised a higher percentage of men (4391 [93.7%] vs 4794 [90.2%]), and were composed of more White non-Hispanic individuals (3366 [71.8%] vs 3259 [61.3%]). Based on AIC, the regression model with survey-based covariates and EHR-based covariates better estimated hospital admission at 90 days (AIC, 1947.7) and 180 days (AIC, 2951.9) than restricted models with only EHR-based covariates (AIC, 1980.2 at 90 days; AIC, 2981.9 at 180 days). This result was due to inclusion of self-reported measures such as marital or partner status, health-related locus of control, resilience, smoking status, health literacy, and medication insecurity. <h3>Conclusions and Relevance</h3> Augmenting EHR data with patient-reported social information improved estimation of 90-day and 180-day hospitalization risk, highlighting specific SDH factors that might identify individuals who are at high risk for hospitalization.
Abstract 10979: Real-world Impact of a Novel Digital Medicine Program on Clinical Outcomes and Total Healthcare Costs in Patients With Drug-refractory Hypertension, Diabetes, and/or Hyperlipidemia
Authors: Xue Wang, Maxfield Frohlich, Lindsey Valenzuela, Cheri Sacks, R. Scooter Plowman, Teresa Hodgkins
Journal: Circulation (2019)

Introduction: Medication adherence is critical to ensure optimal treatment outcomes in patients with chronic conditions. Traditional methods to measure adherence (e.g., self-reporting, refill recor...
Annals Graphic Medicine - Hats
Authors: Zachary G. Jacobs
Journal: Annals of Internal Medicine (2020)

Web Exclusives20 October 2020Annals Graphic Medicine - HatsFREEZachary G. Jacobs, MDZachary G. Jacobs, MDOregon Health & Science University, Portland, Oregon (Z.G.J.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G20-0012 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment DOUG DELONGBassett Healthcare, Cooperstown, NY20 October 2020 Hats off to you Always love this section. Another brilliant one. However, as resident of village where baseball was born [or not], and especially at time of the world series, I would have opted for a baseball cap rather than an inadequate concussion prevention device. Author, Article, and Disclosure InformationAffiliations: Oregon Health & Science University, Portland, Oregon (Z.G.J.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G20-0012.Author/Illustrator Information: Zachary G. Jacobs, MD, is a hospitalist at Oregon Health & Science University. He uses creative writing, photography, and graphic arts to combine his two passions: healing and storytelling. To see more of his work, visit https://zgjmd.wordpress.com. E-mail: [email protected]edu; Twitter: @ZacharyGJacobs. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 October 2020Volume 173, Issue 8Page: W133-W134 ePublished: 20 October 2020 Issue Published: 20 October 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Endothelial extracellular vesicles contain protective proteins and rescue ischemia-reperfusion injury in a human heart-on-chip
Authors: Moran Yadid, Johan U. Lind, Herdeline Ann M. Ardoña, Sean P. Sheehy, Lauren E. Dickinson, Feyisayo Eweje, Maartje M.C. Bastings, Benjamin Pope, Blakely B. O’Connor, Juerg R. Straubhaar, Bogdan Budnik, Andre G. Kleber, Kevin Kit Parker
Journal: Science Translational Medicine (2020)

Endothelial extracellular vesicles containing cardioprotective proteins rescue engineered human cardiac tissue in an ischemia-reperfusion injury model.
Infiltrating pattern and prognostic value of tertiary lymphoid structures in resected non-functional pancreatic neuroendocrine tumors
Authors: Wu-Hu Zhang, Wen-Quan Wang, Xuan Han, He-Li Gao, Shuai-Shuai Xu, Shuo Li, Tian-Jiao Li, Hua-Xiang Xu, Hao Li, Long-Yun Ye, Xuan Lin, Chun-Tao Wu, Jiang Long, Xian-Jun Yu, Liang Liu
Journal: Journal for ImmunoTherapy of Cancer (2020)

Tertiary lymphoid structures (TLS) are associated with favorable survival and play a critical role in most solid tumors. However, investigations of TLS are lacking in patients with grade 1 or grade 2 (G1/G2) non-functional pancreatic neuroendocrine tumors (NF-PanNETs). This study aimed to investigate the presence, cellular composition, association with tumor-infiltrating immune cells, and prognostic value of TLS in G1/G2 NF-PanNETs.Tumor tissues from a 182-patient Fudan cohort and a 125-patient external validation set were assessed by H&E staining, immunohistochemistry, and/or multispectral fluorescent immunohistochemistry.TLS were identified in more than one-third of patients with G1/G2 NF-PanNETs and were located peritumorally, either just outside the tumor tissue or in the stromal area. TLS were mainly composed of B-cell follicles with germinal centers and T-cell zones with dendritic cells. Kaplan-Meier analyses showed that the presence of TLS correlated with both longer recurrence-free survival (RFS, p<0.001) and overall survival (OS, p=0.001), but the number of TLS had no prognostic significance. Multivariate Cox-regression analyses demonstrated that the presence of TLS, WHO classification, and 8th edition American Joint Committee on Cancer (AJCC8th) tumor-node-metastasis (TNM) stage were independent prognostic factors for RFS (p=0.004, p=0.001, and p<0.001, respectively) and OS (p=0.009, p=0.008, and p=0.019, respectively). These results were confirmed using an external validation set. Finally, a nomogram incorporating the presence of TLS was constructed to predict the probability of 5-year RFS of resected G1/G2 NF-PanNETs, which improved on the current WHO classification and AJCC8th TNM stage.The presence of TLS is an independent and favorable predictor of resected G1/G2 NF-PanNETs, which may play a role in cancer immunobiology.
Carboplatin and Paclitaxel for Advanced Endometrial Cancer: Final Overall Survival and Adverse Event Analysis of a Phase III Trial (NRG Oncology/GOG0209)
Authors: David S. Miller, Virginia L. Filiaci, Robert S. Mannel, David E. Cohn, Takashi Matsumoto, Krishnansu S. Tewari, Paul DiSilvestro, Michael L. Pearl, Peter A. Argenta, Matthew A. Powell, Susan L. Zweizig, David P. Warshal, Parviz Hanjani, Michael E. Carney, Helen Huang, David Cella, Richard Zaino, Gini F. Fleming
Journal: Journal of Clinical Oncology (2020)

Limitations of the paclitaxel-doxorubicin-cisplatin (TAP) regimen in the treatment of endometrial cancer include tolerability and cumbersome scheduling. The Gynecologic Oncology Group studied carboplatin plus paclitaxel (TC) as a noninferior alternative to TAP.GOG0209 was a phase III, randomized, noninferiority, open-label trial. Inclusion criteria were stage III, stage IV, and recurrent endometrial cancers; performance status 0-2; and adequate renal, hepatic, and marrow function. Prior radiotherapy and/or hormonal therapy were permitted, but chemotherapy, including radiosensitization, was not. Patients were treated with doxorubicin 45 mg/m2 and cisplatin 50 mg/m2 (day 1), followed by paclitaxel 160 mg/m2 (day 2) with granulocyte colony-stimulating factor or paclitaxel 175 mg/m2 and carboplatin area under the curve 6 (day 1) every 21 days for seven cycles. The primary endpoint was overall survival (OS; modified intention to treat). Progression-free survival (PFS), health-related quality of life (HRQoL), and toxicity were secondary endpoints.From 2003 to 2009, 1,381 women were enrolled. Noninferiority of TC to TAP was concluded for OS (median, 37 v 41 months, respectively; hazard ratio [HR], 1.002; 90% CI, 0.9 to 1.12), and PFS (median, 13 v 14 months; HR, 1.032; 90% CI, 0.93 to 1.15). Neutropenic fever was reported in 7% of patients receiving TAP and 6% of those receiving TC. Grade > 2 sensory neuropathy was recorded in 26% of patients receiving TAP and 20% receiving TC (P = .40). More grade ≥ 3 thrombocytopenia (23% v 12%), vomiting (7% v 4%), diarrhea (6% v 2%), and metabolic (14% v 8%) toxicities were reported with TAP. Neutropenia (52% v 80%) was more common with TC. Small HRQoL differences favored TC.With demonstrated noninferiority to TAP, TC is the global first-line standard for advanced endometrial cancer.
Abstract 10744: The Impact of Polypharmacy on the Predictive Value of Cognitive Function in Patients With Acute Decompensated Heart Failure; Insights From Osaka Prefectural Acute Heart Failure Registry (OPAR)
Authors: Kiyomi Kayama, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Masato Kawasaki, Atsushi Kikuchi, Tsutomu Kawai, Masahiro Seo, Makoto Abe, Jun Nakamura, Kyoko Yamamoto, Masatsugu Kawahira, Kazuya Tanabe
Journal: Circulation (2019)

Background: In heart failure (HF), the use of multiple drugs based on the therapeutic regimen is common and recommended by international guidelines. Furthermore, HF is common disease in the elderly...
Abstract 246: Development of a Reflex Work of Breathing Scale for Easy Implementation Outside Intensive Care Environments
Authors: Raul J Gazmuri, Mylene Apigo, Nyembezi Dhliwayo, Mohammed Al Tameemi, Jeffrey Schechtman
Journal: Circulation (2019)

Introduction: A common misconception is that increased work of breathing (WOB) in hospitalized patients can be ruled-out when arterial O 2 tension (or saturation) is adequate and arterial PCO 2 is not elevated. Unrecognized WOB increase leads to respiratory muscle fatigue, cessation of respiratory function, and cardiac arrest. We previously developed a WOB Scale for bedside use adding points (maximum 7) based on respiratory rate (1 to 20 bpm = 1 point; 21 to 25 bpm = 2 points; 26 to 30 bpm = 3 points; and &gt; 30 bpm = 4 points), nasal flaring (No = 0 points; Yes = 1 point), activation of the sternocleidomastoid muscle (No = 0 points; Yes = 1 point), and activation of abdominal muscles (No = 0 points; Yes = 1 point). A WOB Scale &gt; 3 points typical identifies a patient in need of intervention to reduce or support WOB increase. However, widespread application of our WOB Scale - especially outside intensive care environments - would likely benefit from a simplified approach. Thus, we investigated developing a “reflex” approach whereby measurement of all four components would be contingent on the respiratory rate level. Methods: We analyzed 110 WOB Scale measurements in a mixed population of ICU and General Ward patients and assessed WOB Scale levels hypothesizing that a respiratory rate of 1 point (1 to 20 bpm) would be predictive of a low WOB Scale (i.e., not exceeding 3 points); thus, obviating the need to perform a complete WOB Scale evaluation. Results: The WOB Scale distribution showed that most patients had normal WOB with only 14 patients (12.7%) having a WOB Scale &gt; 3 points (i.e., 1 point = 60; 2 points = 24; 3 points = 12; 4 points = 6; 5 points = 7; 6 points = 1; 7 points = 0). A respiratory rate level of 1 point (i.e., 1 to 20 bpm), occurred in 68 patients and only 3 (1.5%) had a WOB Scale &gt; 3 points. Yet, when the respiratory rate level was 2 points (i.e., 21 to 25 bpm), which occurred in 28 patients, 3 (10.7%) had a WOB Scale &gt; 3 points. Respiratory rate levels of 3 or 4 points (&gt; 26 bpm) were associated with activation of at least one accessory respiratory muscle examined in 64% of the patients. Conclusions: A respiratory rate of 20 bpm or less predicted low WOB in most patients supporting a Reflex WOB Scale whereby respiratory accessory muscle activation is assessed only when the respiratory rate exceeds 20 bpm.
The natural history of vestibular schwannoma growth—prospective 40-year data from an unselected national cohort
Authors: Martin Reznitsky, Mette Marie Babiel Schmidt Petersen, Niels West, Sven-Eric Stangerup, Per Cayé-Thomasen
Journal: Neuro-Oncology (2020)

Optimal management of vestibular schwannoma (VS) is still debated and thus international consensus has not been achieved. Treatment options are observation, radiotherapy, and surgery. Knowledge on the natural history of tumor growth is essential for choice of treatment modality. The aim is to present intra-/extrameatal tumor growth and management data from a prospective, unselected national cohort of patients diagnosed with VS during the period 1976-2015.Since 1976, all data from patients diagnosed with sporadic VS in Denmark have been referred to our national treatment center, where they have been entered prospectively into the national database. Data on tumor localization, growth, and treatment were retrieved. Growth definition: >2 mm by linear measurement, in accordance with the Tokyo 2001 consensus-meeting recommendations.3637 cases of VS were diagnosed, in which 1304 patients had surgery and 21 received radiotherapy post diagnosis. 2312 patients were observed with mean follow-up of 7.33 years. Of these, 434(19%; 102 intra-and 332 extrameatal tumors) changed to active treatment during the observation period due to tumor growth. 5 years after diagnosis, 21% of the intrameatal tumors exhibited growth during observation, whereas 37% of extrameatal tumors had grown, increasing to 25% intrameatal and 42% extrameatal after 10 years. Following growth, the intrameatal tumors were mostly observed further and the extrameatal mostly underwent surgery. Tumor growth occurred mainly within the first 5 years post diagnosis.This natural history study documents the growth occurrence of both intra-and extrameatal VS during the first 12 years after diagnosis and should be used in patient counseling, management, and treatment decision making.
Repolarization of HSC attenuates HSCs failure in Shwachman–Diamond syndrome
Authors: Sachin Kumar, Kalpana J. Nattamai, Aishlin Hassan, Amanda Amoah, Rebekah Karns, Cuiping Zhang, Ying Liang, Akiko Shimamura, M. Carolina Florian, Ute Bissels, Martha Luevano, Andreas Bosio, Stella M. Davies, Medhanie Mulaw, Hartmut Geiger, Kasiani C. Myers
Journal: Leukemia (2020)
Angiotensin-converting enzyme 2 (ACE2): SARS-CoV-2 receptor and RAS modulator
Authors: Jingwei Bian, Zijian Li
Journal: Acta Pharmaceutica Sinica B (2020)

The coronavirus disease 2019 (COVID-19) outbreak is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) was rapidly identified as the critical functional receptor for SARS-CoV-2. ACE2 is well-known as a counter-regulator of the renin-angiotensin system (RAS) and plays a key role in the cardiovascular system. Given that ACE2 functions as both a SARS-CoV-2 receptor and a RAS modulator, the treatment for COVID-19 presents a dilemma of how to limit virus entry but protect ACE2 physiological functions. Thus, an in-depth summary of the recent progress of ACE2 research and its relationship to the virus is urgently needed to provide possible solution to the dilemma. Here, we summarize the complexity and interplay between the coronavirus, ACE2 and RAS (including anti-RAS drugs). We propose five novel working modes for functional receptor for SARS-CoV-2 infection and the routes of ACE2-mediated virus entering host cells, as well as its regulatory mechanism. For the controversy of anti-RAS drugs application, we also give theoretical analysis and discussed for drug application. These will contribute to a deeper understanding of the complex mechanisms of underlying the relationship between the virus and ACE2, and provide guidance for virus intervention strategies.