tbuckley/cabot-search huggingface dataset:
Effect of point-of-care C-reactive protein testing on antibiotic prescription in febrile patients attending primary care in Thailand and Myanmar: an open-label, randomised, controlled trial
Authors: Thomas Althaus, Rachel C Greer, Myo Maung Maung Swe, Joshua Cohen, Ni Ni Tun, James Heaton, Supalert Nedsuwan, Daranee Intralawan, Nithima Sumpradit, Sabine Dittrich, Zoë Doran, Naomi Waithira, Hlaing Myat Thu, Han Win, Janjira Thaipadungpanit, Prapaporn Srilohasin, Mavuto Mukaka, Pieter W Smit, Ern Nutcha Charoenboon, Marco Johannes Haenssgen, Tri Wangrangsimakul, Stuart Blacksell, Direk Limmathurotsakul, Nicholas Day, Frank Smithuis, Yoel Lubell
Journal: The Lancet Global Health (2018)

In southeast Asia, antibiotic prescription in febrile patients attending primary care is common, and a probable contributor to the high burden of antimicrobial resistance. The objective of this trial was to explore whether C-reactive protein (CRP) testing at point of care could rationalise antibiotic prescription in primary care, comparing two proposed thresholds to classify CRP concentrations as low or high to guide antibiotic treatment.
Universal health coverage in Indonesia: concept, progress, and challenges
Authors: Rina Agustina, Teguh Dartanto, Ratna Sitompul, Kun A Susiloretni, None Suparmi, Endang L Achadi, Akmal Taher, Fadila Wirawan, Saleha Sungkar, Pratiwi Sudarmono, Anuraj H Shankar, Hasbullah Thabrany, Rina Agustina, Teguh Dartanto, Ratna Sitompul, Kun Aristiati Susiloretni, None Suparmi, Endang L Achadi, Akmal Taher, Fadila Wirawan, Saleha Sungkar, Pratiwi Sudarmono, Anuraj H Shankar, Hasbullah Thabrany, Prastuti Soewondo, Sitti Airiza Ahmad, Muhammad Kurniawan, Budi Hidayat, Donald Pardede, None Mundiharno, Erni J Nelwan, Okky Lupita, Ery Setyawan, Atik Nurwahyuni, Dwi Martiningsih, Helda Khusun
Journal: The Lancet (2018)
Greetings from the editor 2019
Authors: Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2018)

First of all, let me wish you a healthy, happy and prosperous New Year—may your personal and professional wishes come true. Second, let me thank you for your continued support of the Annals of the Rheumatic Diseases (ARD) —as readers, as authors, as reviewers or as members of our team. Finally, please allow me to look back at the past year from the perspective of the Editor.

As I had promised in my previous greetings note,1 we started three new sections in 2018: ‘Views on News’, ‘Heroes and Pillars of Rheumatology’ and ‘Thinking the Unthinkable’. Three ‘Views on News’ were published last year and conveyed what the authors thought were publications in other journals with important implications for our field.2–4 A first publication on a hero in the ‘Heroes and Pillars of Rheumatology’ part has also appeared,5 a section intended to tell the younger rheumatologists about people (or publications) that paved the roads to modern rheumatology—more will follow. Finally, ARD also made an initial blink into the ‘unthinkable’ future,6 which already elicited an interesting online discussion.7 8 

A RD has also promised to provide readers with actual data for all data points in all figures in articles on clinical trials.1 This is in the process of implementation, as can be seen already in some trial papers published in recent months; the data are shown either directly in the publication (such as in ref 9) or in supplementary materials (such as …
A Patient With an Elevated α-Fetoprotein Level and Liver Masses
Authors: Adam E. Mikolajczyk, Lindsay J. Yassan, Anjana A. Pillai
Journal: JAMA (2018)

A 55-year-old man with several weeks of malaise, a 6.8-kg weight loss, a CT scan with multifocal liver masses and elevated alkaline phosphatase, ALT, and AFP levels had a heterogeneously enhancing pancreatic-tail mass on triple-phase CT. What would you do next?
Migraine (Japanese Version)
Authors: E. Anne MacGregor
Journal: Annals of Internal Medicine (2017)

In the Clinic4 April 2017Migraine (Japanese Version)Correction(s) for this article:CorrectionsNov 2022Correction: Japanese Translations of In the ClinicFREEE. Anne MacGregor, MB BS, MDE. Anne MacGregor, MB BS, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/IsTranslatedFrom_AITC201704040_Japanese SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Editors' Note: This article (available in PDF format) is the translated Japanese version of In the Clinic: Migraine (MacGregor EA. Migraine. Ann Intern Med. 2017;166:ITC49-ITC64. doi:10.7326/AITC201704040). Author, Article, and Disclosure InformationAffiliations: Correction: This article was updated on 1 November 2022 to remove the glossary of terms, which was not present on the original publication, and to indicate the translators of the article.Funding Source: American College of Physicians.Disclosures: Dr. MacGregor, ACP Contributing Author, reports personal fees from Menarini outside the submitted work. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-0193.With the assistance of additional physician writers, the editors of Annals of Internal Medicine develop In the Clinic using MKSAP and other resources of the American College of Physicians.In the Clinic does not necessarily represent official ACP clinical policy. For ACP clinical guidelines, please go to https://www.acponline.org/clinical_information/guidelines/. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMigraine E. Anne MacGregor Correction: Japanese Translations of In the Clinic Metrics Cited byCorrection: Japanese Translations of In the Clinic 4 April 2017Volume 166, Issue 7Page: JITC49-JITC64 ePublished: 18 December 2018 Issue Published: 4 April 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Impact of Minimal Residual Disease and Achievement of Complete Remission/Complete Remission with Partial Hematologic Recovery (CR/CRh) on Overall Survival Following Treatment with Gilteritinib in Patients with Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) with FLT3 Mutations
Authors: Mark J. Levis, Alexander E. Perl, Jessica K. Altman, Jorge E. Cortes, Catherine C. Smith, Maria R. Baer, David F. Claxton, Joseph G. Jurcic, Ellen K. Ritchie, Stephen A. Strickland, Raoul Tibes, Jason E. Hill, Matt Rosales, Erkut Bahceci
Journal: Blood (2018)
1-Pyrroline-5-carboxylate released by prostate Cancer cell inhibit T cell proliferation and function by targeting SHP1/cytochrome c oxidoreductase/ROS Axis
Authors: Yutao Yan, Lei Chang, Hongzhe Tian, Lu Wang, Yawei Zhang, Tao Yang, Guohao Li, Weifeng Hu, Kavita Shah, Gang Chen, Yonglian Guo
Journal: Journal for ImmunoTherapy of Cancer (2018)

Tumor cell mediated immune-suppression remains a question of interest in tumor biology. In this study, we focused on the metabolites that are released by prostate cancer cells (PCC), which could potentially attenuate T cell immunity. Prostate cancer cells (PCC) media (PCM) was used to treat T cells, and its impact on T cell signaling was evaluated. The molecular mechanism was further verified in vivo using mouse models. The clinical significance was determined using IHC in human clinical specimens. Liquid chromatography mass spectroscopy (LC/MS-MS) was used to identify the metabolites that are released by PCC, which trigger T cells inactivation. PCM inhibits T cells proliferation and impairs their ability to produce inflammatory cytokines. PCM decreases ATP production and increases ROS production in T cells by inhibiting complex III of the electron transport chain. We further show that SHP1 as the key molecule that is upregulated in T cells in response to PCM, inhibition of which reverses the phenotype induced by PCM. Using metabolomics analysis, we identified 1-pyrroline-5-carboxylate (P5C) as a vital molecule that is released by PCC. P5C is responsible for suppressing T cells signaling by increasing ROS and SHP1, and decreasing cytokines and ATP production. We confirmed these findings in vivo, which revealed changed proline dehydrogenase (PRODH) expression in tumor tissues, which in turn influences tumor growth and T cell infiltration. Our study uncovered a key immunosuppressive axis, which is triggered by PRODH upregulation in PCa tissues, P5C secretion in media and subsequent SHP1-mediated impairment of T cell signaling and infiltration in PCa.
Associations of Hemoglobin A1c With Cardiovascular Disease and Mortality in Chinese Adults With Diabetes
Authors: Jieli Lu, Weiqing Wang, Mian Li, Yufang Bi, Yu Xu, Lulu Chen, Jiajun Zhao, Yiming Mu, Ralph A. DeFronzo, Guang Ning
Journal: Journal of the American College of Cardiology (2018)
High cortactin expression in B-cell acute lymphoblastic leukemia is associated with increased transendothelial migration and bone marrow relapse
Authors: Martha Velázquez-Avila, Juan Carlos Balandrán, Dalia Ramírez-Ramírez, Mirella Velázquez-Avila, Antonio Sandoval, Alfonso Felipe-López, Porfirio Nava, José Antonio Alvarado-Moreno, David Dozal, Jessica L. Prieto-Chávez, Matthias Schaks, Klemens Rottner, Elisa Dorantes-Acosta, Briceida López-Martínez, Michael Schnoor, Rosana Pelayo
Journal: Leukemia (2018)

Cancer is a major cause of death in children worldwide, with B-lineage cell acute lymphoblastic leukemia (B-ALL) being the most frequent childhood malignancy. Relapse, treatment failure and organ infiltration worsen the prognosis, warranting a better understanding of the implicated mechanisms. Cortactin is an actin-binding protein involved in cell adhesion and migration that is overexpressed in many solid tumors and in adult B-cell chronic lymphocytic leukemia. Here, we investigated cortactin expression and potential impact on infiltration and disease prognosis in childhood B-ALL. B-ALL cell lines and precursor cells from bone marrow (BM) and cerebrospinal fluid (CSF) of B-ALL patients indeed overexpressed cortactin. In CXCL12-induced transendothelial migration assays, transmigrated B-ALL cells had highest cortactin expression. In xenotransplantation models, only cortactinhigh-leukemic cells infiltrated lungs, brain, and testis; and they colonized more easily hypoxic BM organoids. Importantly, cortactin-depleted B-ALL cells were significantly less efficient in transendothelial migration, organ infiltration and BM colonization. Clinical data highlighted a significant correlation between high cortactin levels and BM relapse in drug-resistant high-risk B-ALL patients. Our results emphasize the importance of cortactin in B-ALL organ infiltration and BM relapse and its potential as diagnostic tool to identify high-risk patients and optimize their treatments.
Combination of Nilotinib and Pegylated Interferon Alfa-2b Results in High Molecular Response Rates in Chronic Phase CML: Interim Results of the ALLG CML 11 Pinnacle Study
Authors: David T Yeung, Andrew P. Grigg, Naranie Shanmuganathan, Ilona Cunningham, Jake Shortt, Philip Rowling, John Reynolds, Rachel Cushion, Rosemary Anne Harrup, David M Ross, David Kipp, Anthony K Mills, Christopher K Arthur, Anthony P Schwarer, Kathryn Jackson, Nicholas Viiala, Robert Weinkove, Agnes S. M. Yong, Deborah L White, Susan Branford, Timothy P. Hughes, On Behalf of the ALLG
Journal: Blood (2018)
Abstract 19606: PZ-128: First in Human Pepducin Inhibitor of PAR-1 Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability
Authors: Paul A Gurbel, Kevin P Bliden, Udaya S Tantry, Susan E Turner, Martin Gesheff, Lidija Covic, Athan Kuliopulos
Journal: Circulation (2015)

Background: PZ-128 is a first-in-class cell penetrating lipopeptide pepducin that inhibits PAR-1-G protein signaling by forming a structure highly similar to the corresponding off-state juxtamembrane region of the GPCR. PZ-128 inhibited PAR-1 and thrombosis in non-human primates. Its effects in humans are unknown. Methods and Results: PZ-128 was administered by continuous intravenous infusion (0.01 mg/kg to 2 mg/kg) to patients with multiple cardiovascular risk factors (n=31). Safety, tolerability, and pharmacokinetic (PK) effects were assessed. Platelet receptor function was assessed by conventional aggregation at baseline and 0.5, 1, 2, 6, 24 h and 8-11 d post-dosing. There were no effects on ECG, hematologic or clinical chemistry parameters. At 0.5 mg/kg given over 2 h there was 40 % and 50 % inhibition (8 μM SFLLRN) at 0.5 and 2 h, respectively. At 1-2 mg/kg, there was 25% and 75% inhibition at 0.5 h and 95-100% inhibition at 1-2 h (p&lt;0.05 for 1 mg dose). Maximal platelet aggregation (8 μM SFLLRN) was 66-100% recovered by 24 h at 0.5-2 mg/kg. There was no significant inhibition of PAR-4, ADP, or collagen receptors at any time point. PZ-128 plasma levels were linear with dose (R=0.99) and reached Cmax levels of 2 μM, 2.5 μM, 5 μM, and 12 μM at 0.3, 0.5, 1 and 2 mg/kg doses, respectively. The terminal elimination plasma half-life was 49 ± 6 min. Conclusion: PZ-128 is a promising parenteral antiplatelet agent that provided rapid, specific, dose-dependent, and reversible inhibition of platelet PAR-1 through a novel mechanism.
An explainable deep-learning algorithm for the detection of acute intracranial haemorrhage from small datasets
Authors: Hyunkwang Lee, Sehyo Yune, Mohammad Mansouri, Myeongchan Kim, Shahein H. Tajmir, Claude E. Guerrier, Sarah A. Ebert, Stuart R. Pomerantz, Javier M. Romero, Shahmir Kamalian, Ramon G. Gonzalez, Michael H. Lev, Synho Do
Journal: Nature Biomedical Engineering (2018)
Tim Evans: respiratory medicine and intensive care physician who advised the Department of Health on clinical productivity
Authors: Janet Fricker
Journal: BMJ (2018)

Tim Evans was a respiratory physician whose sphere of influence grew ever wider as his career evolved. He made his first contribution as a respiratory intensive care consultant at the Royal Brompton and Harefield NHS Foundation Trust (RBHFT). This was followed with administrative roles as medical director and deputy chief executive, and finally he was seconded to the Department of Health as national director for clinical productivity, where he strove to reduce unwarranted variation in practice.

Evans’s achievements included helping to establish intensive care medicine as a recognised specialty in the UK, and becoming a world authority on cardiothoracic intensive care, acute respiratory distress syndrome (ARDS), and extracorporeal membrane oxygenation (ECMO). In addition, his translational research, with many national and international collaborators, advanced understanding of the pathobiology of ARDS and sepsis.

“Tim’s ultimate legacy was using talents he’d accrued over 30 years working in clinical practice and management to drive change in the NHS, improving quality of care and providing best value,” said Tim Briggs, national director for clinical quality and efficiency for the NHS, who worked with Evans on the Getting It Right First Time programme. “In his final role, Tim made a difference not just to his own patients but to the lives of millions of people across the UK. It was a heck of an achievement.”

Evans’s administrative career took flight in 2010 when as academic vice president of the Royal College of Physicians (RCP) he was involved in writing Hospitals on the Edge? The Time for Action , published in September 2012.1 The report set out the magnitude of challenges facing acute hospital services after the Mid Staffs scandal. Next, Evans conceived the idea for the RCP’s future hospital commission, resulting in publication of Future Hospitals: Caring for Medical Patients in 2013, setting out the …
Abstract 21365: Intralipid Fails to Rescue Liposomal Bupivacaine (Exparel)-Induced Cardiac Arrest in Rats
Authors: Marsha Bernardo, Nancy Cao, Shayan Moazeni, Anamaria Marijic Buljubasic, Andriana Marijic Buljubasic, Siamak Rahman, Mansoureh Eghbali, Soban Umar
Journal: Circulation (2017)

Background: Exparel is a formulation of bupivacaine encapsulated in multi-vesicular liposomes, developed for post-surgical anesthesia. The liposomes have been shown to increase the drug’s stability and extend its duration of action. Exparel may prevent accumulation of bupivacaine in blood and/or tissue; thus, decreasing risk of central nervous or cardiovascular toxicities. However, administration of Exparel has its risks. The maximum dosage of Exparel for adults is ~266 mg, but the maximum mg/kg dosing limit is unknown. The role of Intralipid (ILP, 20%) for reversal of Exparel toxicity is not known. Our aim is to determine toxic dose of Exparel in mg/kg and if ILP can reverse its cardiotoxic effects in rats. Methods: Female rats (~250 gm, n=6) were used for the study. Asystole was attempted with different IV doses of Exparel (25 mg/kg, 15 mg/kg, 7.5mg/kg over 10 seconds). For the second part of the study, asystole was induced with Exparel (15 mg/kg over 10 sec, IV), and resuscitation with ILP (5 ml/kg bolus and 0.5 ml/kg/min maintenance) was started immediately along with chest compressions. Heart rate (HR, beats per min) and ejection fraction (EF, %) were measured using echo at 1, 5, and 10 min. Results: We found that a dose of 25 mg/kg of Exparel caused cardiac arrest immediately. Next we decreased the dose of Exparel to 15 mg/kg, that also caused immediate cardiovascular collapse. Exparel 7.5 mg/kg did not induce cardiac arrest; instead, it caused wide complex tachycardia that self resolved in 5 min. ILP rescue of Exparel cardiotoxicity was found to be unpredictable (n=3). EF, HR and EKG improved after cardiac arrest the most at 1 min after ILP. At 1 min, EF was 42.8+/-15% and HR was 169.3 +/- 25 bpm. ILP rescue of Exparel cardiotoxicity was not sustained contrary to ILP’s rescue of Bupivacaine cardiotoxicity in rats. EF and HR continued to deteriorate when measured at 5 and 10 min, with 2 out of 3 rats with EF=0 at 5 and 10 min. Conclusion: We found a dose of Exparel that reliably induced cardiotoxicity in rats. ILP is unreliable in rescuing Exparel induced cardiotoxicity at the dosage regimen typically used for rats with Bupivacaine cardiotoxicity. More experiments are needed to determine ILP’s dosage that can reliably reverse Exparel cardiotoxicity.
Abstract 12572: Stroke Volume and Cardiovascular Event Risk in Heart Failure With Preserved Ejection Fraction
Authors: Shinya Ito, Takeshi Kitai, Takafumi Yamane, Kitae Kim, Mitsuhiko Ota, Yasuhiro Sasaki, Natsuhiko Ehara, Atsushi Kobori, Makoto Kinoshita, Shuichiro Kaji, Yutaka Furukawa
Journal: Circulation (2015)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a significant and increasing public health problem, which has similar outcomes to HF with reduced EF (HFrEF). However, the prognostic factors of HFpEF have not been clarified. Recently, it has been reported that stroke volume (SV) is often reduced in HFpEF patients regardless of preserved EF. This study aimed to determine the importance of SV assessment on clinical outcomes in patients with HFpEF. Methods: We retrospectively reviewed 699 consecutive patients with acutely decompensated heart failure who were admitted in our institution between 2009 and 2011. Among them, both baseline and follow-up data including echocardiography were available in 425 patients. The patients were divided into 3 groups; EF≥50% (HFpEF), 41-49% (borderline), and EF&lt;40%(HFrEF), and clinical outcomes were compared among the groups. SV was estimated noninvasively from LV volume obtained by transthoracic echocardiography. Results: The mean follow-up period was 2.4±1.8 years. There were 176 patients (41%) with HFpEF, 70 (16%) with borderline and 182 (43%) with HFrEF. There were no significant differences among the 3 groups with respect to actuarial survival (67% vs 58% vs 68%, P=0.33), and event-free survival, defined as a composite of death from any cause, HF readmission, myocardial infarction and stroke (44% vs 33% vs 40%, P=0.20) at 3 years. In HFpEF patients, there were 48 patients (28%) with low SV (&lt;35ml) who had significantly worse outcomes than those with preserved SV (≥35ml) regarding all-cause mortality and cardiovascular events (Figure). Conclusions: Low SV regardless of preserved EF could be a possible marker for high risk patients with HFpEF.
CaV2.1 α1 Subunit Expression Regulates Presynaptic CaV2.1 Abundance and Synaptic Strength at a Central Synapse
Authors: Matthias Lübbert, R. Oliver Goral, Christian Keine, Connon Thomas, Debbie Guerrero-Given, Travis Putzke, Rachel Satterfield, Naomi Kamasawa, Samuel M. Young
Journal: Neuron (2018)
COPD and Cardiovascular Disease
Authors: S. André, B. Conde, E. Fragoso, J.P. Boléo-Tomé, V. Areias, J. Cardoso
Journal: Pulmonology (2018)

COPD is one of the major public health problems in people aged 40 years or above. It is currently the 4th leading cause of death in the world and projected to be the 3rd leading cause of death by 2020. COPD and cardiac comorbidities are frequently associated. They share common risk factors, pathophysiological processes, signs and symptoms, and act synergistically as negative prognostic factors. Cardiac disease includes a broad spectrum of entities with distinct pathophysiology, treatment and prognosis. From an epidemiological point of view, patients with COPD are particularly vulnerable to cardiac disease. Indeed, mortality due to cardiac disease in patients with moderate COPD is higher than mortality related to respiratory failure. Guidelines reinforce that the control of comorbidities in COPD has a clear benefit over the potential risk associated with the majority of the drugs utilized. On the other hand, the true survival benefits of aggressive treatment of cardiac disease and COPD in patients with both conditions have still not been clarified. Given their relevance in terms of prevalence and prognosis, we will focus in this paper on the management of COPD patients with ischemic coronary disease, heart failure and dysrhythmia.
Chronic Q fever-related complications and mortality: data from a nationwide cohort
Authors: S.E. van Roeden, P.C. Wever, L.M. Kampschreur, P. Gruteke, W. van der Hoek, A.I.M. Hoepelman, C.P. Bleeker-Rovers, J.J. Oosterheert
Journal: Clinical Microbiology and Infection (2018)