tbuckley/cabot-search huggingface dataset:
Preeclampsia
Authors: Sarosh Rana, Elizabeth Lemoine, Joey P. Granger, S. Ananth Karumanchi
Journal: Circulation Research (2019)

Hypertensive disorders of pregnancy—chronic hypertension, gestational hypertension, and preeclampsia—are uniquely challenging as the pathology and its therapeutic management simultaneously affect mother and fetus, sometimes putting their well-being at odds with each other. Preeclampsia, in particular, is one of the most feared complications of pregnancy. Often presenting as new-onset hypertension and proteinuria during the third trimester, preeclampsia can progress rapidly to serious complications, including death of both mother and fetus. While the cause of preeclampsia is still debated, clinical and pathological studies suggest that the placenta is central to the pathogenesis of this syndrome. In this review, we will discuss the current evidence for the role of abnormal placentation and the role of placental factors such as the antiangiogenic factor, sFLT1 (soluble fms-like tyrosine kinase 1) in the pathogenesis of the maternal syndrome of preeclampsia. We will discuss angiogenic biomarker assays for disease-risk stratification and for the development of therapeutic strategies targeting the angiogenic pathway. Finally, we will review the substantial long-term cardiovascular and metabolic risks to mothers and children associated with gestational hypertensive disorders, in particular, preterm preeclampsia, and the need for an increased focus on interventional studies during the asymptomatic phase to delay the onset of cardiovascular disease in women.
Advanced endoscopic resection using endoscopic submucosal dissection technique to resect a giant, lumen-occluding esophageal polyp
Authors: Mario Rey Ferro, Raul Pinilla Morales
Journal: Endoscopy (2019)

Fibrovascular polyps tend to appear as lesions of up to 7 cm in length, and cause symptoms that range from dysphagia to episodes of asphyxiation due to prolapse into the respiratory tract [1] [2]. Traditionally, surgical treatment is performed because there is a risk of hemorrhaging during endoscopic resection [3].
A Device on Trial — Intermittent Pneumatic Compression in Critical Care
Authors: François Lauzier, James D. Douketis, Deborah J. Cook
Journal: New England Journal of Medicine (2019)

The intensive care unit (ICU) is replete with devices used for monitoring, prevention, diagnosis, treatment, and rehabilitation in critically ill patients. The approval process for high-risk medical devices in the United States is intended to give reasonable assurance of their safety and effectiveness. For approval of noninvasive and non–life-sustaining moderate-risk devices such as those used for intermittent pneumatic compression, the Food and Drug Administration requirements are less stringent and instead focus on showing "substantial equivalence" to devices already on the market.1 In addition, the postmarketing monitoring of medical devices aims primarily to confirm safety rather than show effectiveness. Consequently, apparently . . .
Changes in Time of Gastric Emptying After Surgical and Endoscopic Bariatrics and Weight Loss: A Systematic Review and Meta-Analysis
Authors: Eric J. Vargas, Fateh Bazerbachi, Gerardo Calderon, Larry J. Prokop, Victoria Gomez, M. Hassan Murad, Andres Acosta, Michael Camilleri, Barham K. Abu Dayyeh
Journal: Clinical Gastroenterology and Hepatology (2019)
Abstract 21323: Intralipid Fails to Rescue Bupivacaine-Induced Cardiac Arrest in Pregnant Rats
Authors: Caitlin Sherman, Nancy Cao, Shayan Moazeni, Mylene Vaillancourt, Anamaria Marijic Buljubasic, Andriana Marijic Buljubasic, Mansoureh Eghbali, Soban Umar
Journal: Circulation (2017)

Background: Pregnant patients routinely get neuraxial anesthesia. Bupivacaine is one of the most commonly used local anesthetics in obstetric anesthesia. Studies have suggested that pregnancy increases Bupivacaine cardiotoxicity. We and others have previously shown that Intralipid (ILP) rescues the heart from Bupivacaine cardiotoxicity in male rats. ILP mediates its cardioprotective effects via glycogen synthase kinase-3b (GSK-3b) phosphorylation. We aimed to investigate Bupivacaine cardiotoxicity and potential for ILP’s rescue in pregnant rats, that has not been studied before. Methods: Late pregnant rats (200-300 g, n=12) at day 20 of pregnancy were used for the study. A group of pregnant rats received Bupivacaine bolus (10 mg/kg, IV over ~20 seconds, n=7) to induce asystole under anesthesia. Resuscitation with ILP 20% (5 ml/kg bolus, and 0.5 ml/kg/min maintenance, n=7) and chest compressions were initiated. The ejection-fraction (EF%), and heart rate (HR) were calculated from echocardiography and EKG at baseline and at 1, 5, and 10 min after ILP treatment. A group of pregnant rats that did not undergo Bupivacaine-induced cardiac arrest and ILP rescue served as sham controls (n=5). Hearts were collected and Western blot was performed to assess GSK-3b phosphorylation. Results: All 7 late pregnant rats developed cardiac arrest a few seconds after Bupivacaine. Interestingly, 6 out of the 7 rats were not rescued with ILP using the same dose as in male rats. In these 6 rats, the average baseline EF and HR were 67.344.47% and 34130.44 bpm. One, five and ten minutes after ILP administration, the EF and HR were 0. Western blots showed that pregnant rats which were not rescued by ILP failed to have GSK-3b activation (pGSK/GSK=0.80±0.51 vs. 1.00±0.56 in late pregnant sham controls; p=0.578). In the late pregnant rat that recovered with ILP, baseline EF and HR (66.302.99% and 31034 bpm), were not different than the rats that did not recover. Conclusions: ILP failed to rescue Bupivacaine-induced cardiac arrest in pregnant rats. This failure of rescue is most likely attributed to the inability of ILP to activate GSK-3b, a known mediator of ILP’s cardioprotection.
Immunological methods for diagnosis and monitoring of IgE‐mediated allergy caused by industrial sensitizing agents (IMExAllergy)
Authors: Xaver Baur, Cezmi A. Akdis, Lygia Therese Budnik, Maria Jesus Cruz, Axel Fischer, Ulrike Förster‐Ruhrmann, Thomas Göen, Ozlem Goksel, Astrid R. Heutelbeck, Meinir Jones, Harald Lux, Piero Maestrelli, Xavier Munoz, Benoit Nemery, Vivi Schlünssen, Torben Sigsgaard, Claudia Traidl‐Hoffmann, Paul Siegel
Journal: Allergy (2019)

Abstract Industrial sensitizing agents (allergens) in living and working environments play an important role in eliciting type 1 allergic disorders including asthma and allergic rhinitis. Successful management of allergic diseases necessitates identifying their specific causes (ie, identify the causative agent(s) and the route of contact to allergen: airborne, or skin contact) to avoid further exposure. Identification of sensitization by a sensitive and validated measurement of specific IgE is an important step in the diagnosis. However, only a limited number of environmental and occupational allergens are available on the market for use in sIgE testing. Accordingly, specific in‐house testing by individual diagnostic and laboratory centers is often required. Currently, different immunological tests are in use at various diagnostic centers that often produce considerably divergent results, mostly due to lack of standardized allergen preparation and standardized procedures as well as inadequate quality control. Our review and meta‐analysis exhibited satisfactory performance of sIgE detection test for most high molecular weight (HMW) allergens with a pooled sensitivity of 0.74 and specificity of 0.71. However, for low molecular weight (LMW) allergens, pooled sensitivity is generally lower (0.28) and specificity higher (0.89) than for HMW tests. Major recommendations based on the presented data include diagnostic use of sIgE to HMW allergens. A negative sIgE result for LMW agents does not exclude sensitization. In addition, the requirements for full transparency of the content of allergen preparations with details on standardization and quality control are underlined. Development of standard operating procedures for in‐house sIgE assays, and clinical validation, centralized quality control and audits are emphasized. There is also a need for specialized laboratories to provide a custom service for the development of tests for the measurement of putative novel occupational allergens that are not commercially available.
Abstract 13166: The Sodium-Glucose Co-Transporter 2 Inhibitor Empagliflozin Exhibits Cardiac and Renal Protection in Hypertensive Heart Failure Rats
Authors: Hsiang-Chun Lee, Yi-Lin Shiou, Shih-Jie Jhou, Chia-Yuan Chang, Po-Len Liu, Wun-Jyun Jhuang, An-Sheng Lee
Journal: Circulation (2018)

Introduction: Sodium glucose co-transporter 2 inhibitor (SGLT2i), a new class of anti-diabetic medicine acting on inhibiting glucose resorption by kidneys, is shown beneficial in reduction of heart...
Discontinuing Psychotropic Drugs from Participants in Randomized Controlled Trials: A Systematic Review
Authors: David Cohen, Alexander Recalt
Journal: Psychotherapy and Psychosomatics (2019)

&lt;b&gt;&lt;i&gt;Background and Objective:&lt;/i&gt;&lt;/b&gt; Methods and justifications for discontinuing psychotropic drugs in randomized controlled trials (RCTs), and RCTs’ acknowledgement of possible withdrawal symptoms following discontinuation, have not been examined systematically, which this review aims to do. &lt;b&gt;&lt;i&gt;Study Eligibility, Data Extraction, and Synthesis:&lt;/i&gt;&lt;/b&gt; Publications in MEDLINE, EMBASE, and PsycINFO (2000–2017) randomly assigning participants diagnosed with mental disorders to discontinue antipsychotic, antidepressant, anticonvulsant, antimanic, mood-stabilizing, benzodiazepine, or stimulant drugs. Authors independently extracted data, devised a typology of trials, and assessed trials’ recognition of with­drawal symptoms. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Eighty RCTs (70% with industry participation) discontinued drugs from 5,757 participants to investigate relapse prevention (44%), successful dis­continuation (26%), architecture of withdrawal (14%), and practicality of discontinuation (10%). RCTs of stimulants, antidepressants, and antipsychotics mostly aimed to reach conclusions about relapse prevention by testing abrupt or rapid discontinuations; RCTs of benzodiazepines mostly aimed to reduce drug use by testing longer-lasting, supportive discontinuations. In 67% of RCTs, no justification was given for the specific discontinuation strategy, which lasted under 2 weeks in 60% of RCTs. Possible withdrawal confounding of trial outcomes was addressed in 14% of eligible RCTs. &lt;b&gt;&lt;i&gt;Limitations:&lt;/i&gt;&lt;/b&gt; Only the published literature was searched. &lt;b&gt;&lt;i&gt;Conclusions and Implications:&lt;/i&gt;&lt;/b&gt; RCTs use drug discontinuation to study several key issues in psychopharmacology but infrequently justify how they implement it or acknowledge that possible withdrawal symptoms may threaten internal validity. Reappraising the use of drug discontinuation and the recognition of withdrawal symptoms in RCTs is required.
Survival in Out-of-Hospital Cardiac Arrest After Standard Cardiopulmonary Resuscitation or Chest Compressions Only Before Arrival of Emergency Medical Services
Authors: Gabriel Riva, Mattias Ringh, Martin Jonsson, Leif Svensson, Johan Herlitz, Andreas Claesson, Therese Djärv, Per Nordberg, Sune Forsberg, Sten Rubertsson, Anette Nord, Mårten Rosenqvist, Jacob Hollenberg
Journal: Circulation (2019)

Background: In out-of-hospital cardiac arrest, chest compression–only cardiopulmonary resuscitation (CO-CPR) has emerged as an alternative to standard CPR (S-CPR), using both chest compressions and rescue breaths. Since 2010, CPR guidelines recommend CO-CPR for both untrained bystanders and trained bystanders unwilling to perform rescue breaths. The aim of this study was to describe changes in the rate and type of CPR performed before the arrival of emergency medical services (EMS) during 3 consecutive guideline periods in correlation to 30-day survival. Methods: All bystander-witnessed out-of-hospital cardiac arrests reported to the Swedish register for cardiopulmonary resuscitation in 2000 to 2017 were included. Nonwitnessed, EMS-witnessed, and rescue breath–only CPR cases were excluded. Patients were categorized as receivers of no CPR (NO-CPR), S-CPR, or CO-CPR before EMS arrival. Guideline periods 2000 to 2005, 2006 to 2010, and 2011 to 2017 were used for comparisons over time. The primary outcome was 30-day survival. Results: A total of 30 445 patients were included. The proportions of patients receiving CPR before EMS arrival changed from 40.8% in the first time period to 58.8% in the second period, and to 68.2% in the last period. S-CPR changed from 35.4% to 44.8% to 38.1%, and CO-CPR changed from 5.4% to 14.0% to 30.1%, respectively. Thirty-day survival changed from 3.9% to 6.0% to 7.1% in the NO-CPR group, from 9.4% to 12.5% to 16.2% in the S-CPR group, and from 8.0% to 11.5% to 14.3% in the CO-CPR group. For all time periods combined, the adjusted odds ratio for 30-day survival was 2.6 (95% CI, 2.4–2.9) for S-CPR and 2.0 (95% CI, 1.8–2.3) for CO-CPR, in comparison with NO-CPR. S-CPR was superior to CO-CPR (adjusted odds ratio, 1.2; 95% CI, 1.1–1.4). Conclusions: In this nationwide study of out-of-hospital cardiac arrest during 3 periods of different CPR guidelines, there was an almost a 2-fold higher rate of CPR before EMS arrival and a concomitant 6-fold higher rate of CO-CPR over time. Any type of CPR was associated with doubled survival rates in comparison with NO-CPR. These findings support continuous endorsement of CO-CPR as an option in future CPR guidelines because it is associated with higher CPR rates and overall survival in out-of-hospital cardiac arrest.
Hemap: An Interactive Online Resource for Characterizing Molecular Phenotypes across Hematologic Malignancies
Authors: Petri Pölönen, Juha Mehtonen, Jake Lin, Thomas Liuksiala, Sergei Häyrynen, Susanna Teppo, Artturi Mäkinen, Ashwini Kumar, Disha Malani, Virva Pohjolainen, Kimmo Porkka, Caroline A. Heckman, Patrick May, Ville Hautamäki, Kirsi J. Granberg, Olli Lohi, Matti Nykter, Merja Heinäniemi
Journal: Cancer Research (2019)

Large collections of genome-wide data can facilitate the characterization of disease states and subtypes, permitting pan-cancer analysis of molecular phenotypes and evaluation of disease context for new therapeutic approaches. We analyzed 9,544 transcriptomes from more than 30 hematologic malignancies, normal blood cell types, and cell lines, and showed that disease types could be stratified in a data-driven manner. We then identified cluster-specific pathway activity, new biomarkers, and in silico drug target prioritization through interrogation of drug target databases. Using known vulnerabilities and available drug screens, we highlighted the importance of integrating molecular phenotype with drug target expression for in silico prediction of drug responsiveness. Our analysis implicated BCL2 expression level as an important indicator of venetoclax responsiveness and provided a rationale for its targeting in specific leukemia subtypes and multiple myeloma, linked several polycomb group proteins that could be targeted by small molecules (SFMBT1, CBX7, and EZH1) with chronic lymphocytic leukemia, and supported CDK6 as a disease-specific target in acute myeloid leukemia. Through integration with proteomics data, we characterized target protein expression for pre-B leukemia immunotherapy candidates, including DPEP1. These molecular data can be explored using our publicly available interactive resource, Hemap, for expediting therapeutic innovations in hematologic malignancies. SIGNIFICANCE: This study describes a data resource for researching derailed cellular pathways and candidate drug targets across hematologic malignancies.
Correction to: Treatment duration with immune-based therapies in Cancer: an enigma
Authors: Shanta Bantia, Nirmal Choradia
Journal: Journal for ImmunoTherapy of Cancer (2019)

Following publication of the original article [1], the authors reported an error in the typesetting of their article. The first section of the main text was mistakenly included in the abstract. The original article can be found online at 10.1186/s40425-018-0465-0
Inhibition of the Hypoxia-Inducible Factor 1α–Induced Cardiospecific HERNA1 Enhance-Templated RNA Protects From Heart Disease
Authors: Peter Mirtschink, Corinne Bischof, Minh-Duc Pham, Rahul Sharma, Sanjay Khadayate, Geetha Rossi, Niklaus Fankhauser, Shuyang Traub, Samuel Sossalla, Eman Hagag, Corinne Berthonneche, Alexandre Sarre, Sebastian. N. Stehr, Phillip Grote, Thierry Pedrazzini, Stefanie Dimmeler, Wilhelm Krek, Jaya Krishnan
Journal: Circulation (2019)

Enhancers are genomic regulatory elements conferring spatiotemporal and signal-dependent control of gene expression. Recent evidence suggests that enhancers can generate noncoding enhancer RNAs, but their (patho)biological functions remain largely elusive.We performed chromatin immunoprecipitation-coupled sequencing of histone marks combined with RNA sequencing of left ventricular biopsies from experimental and genetic mouse models of human cardiac hypertrophy to identify transcripts revealing enhancer localization, conservation with the human genome, and hypoxia-inducible factor 1α dependence. The most promising candidate, hypoxia-inducible enhancer RNA ( HERNA)1, was further examined by investigating its capacity to modulate neighboring coding gene expression by binding to their gene promoters by using chromatin isolation by RNA purification and λN-BoxB tethering-based reporter assays. The role of HERNA1 and its neighboring genes for pathological stress-induced growth and contractile dysfunction, and the therapeutic potential of HERNA1 inhibition was studied in gapmer-mediated loss-of-function studies in vitro using human induced pluripotent stem cell-derived cardiomyocytes and various in vivo models of human pathological cardiac hypertrophy.HERNA1 is robustly induced on pathological stress. Production of HERNA1 is initiated by direct hypoxia-inducible factor 1α binding to a hypoxia-response element in the histoneH3-lysine27acetylation marks-enriched promoter of the enhancer and confers hypoxia responsiveness to nearby genes including synaptotagmin XVII, a member of the family of membrane-trafficking and Ca2+-sensing proteins and SMG1, encoding a phosphatidylinositol 3-kinase-related kinase. Consequently, a substrate of SMG1, ATP-dependent RNA helicase upframeshift 1, is hyperphoshorylated in a HERNA1- and SMG1-dependent manner. In vitro and in vivo inactivation of SMG1 and SYT17 revealed overlapping and distinct roles in modulating cardiac hypertrophy. Finally, in vivo administration of antisense oligonucleotides targeting HERNA1 protected mice from stress-induced pathological hypertrophy. The inhibition of HERNA1 postdisease development reversed left ventricular growth and dysfunction, resulting in increased overall survival.HERNA1 is a novel heart-specific noncoding RNA with key regulatory functions in modulating the growth, metabolic, and contractile gene program in disease, and reveals a molecular target amenable to therapeutic exploitation.
The emergence of melatonin in oncology: Focus on colorectal cancer
Authors: Emilio Gil‐Martín, Javier Egea, Russel J. Reiter, Alejandro Romero
Journal: Medicinal Research Reviews (2019)

Within the last few decades, melatonin has increasingly emerged in clinical oncology as a naturally occurring bioactive molecule with substantial anticancer properties and a pharmacological profile optimal for joining the currently available pharmacopeia. In addition, extensive experimental data shows that this chronobiotic agent exerts oncostatic effects throughout all stages of tumor growth, from initial cell transformation to mitigation of malignant progression and metastasis; additionally, melatonin alleviates the side effects and improves the welfare of radio/chemotherapy-treated patients. Thus, the support of clinicians and oncologists for the use of melatonin in both the treatment and proactive prevention of cancer is gaining strength. Because of its epidemiological importance and symptomatic debut in advanced stages of difficult clinical management, colorectal cancer (CRC) is a preferential target for testing new therapies. In this regard, the development of effective forms of clinical intervention for the improvement of CRC outcome, specifically metastatic CRC, is urgent. At the same time, the need to reduce the costs of conventional anti-CRC therapy results is also imperative. In light of this status quo, the therapeutic potential of melatonin, and the direct and indirect critical processes of CRC malignancy it modulates, have aroused much interest. To illuminate the imminent future on CRC research, we focused our attention on the molecular mechanisms underlying the multiple oncostatic actions displayed by melatonin in the onset and evolution of CRC and summarized epidemiological evidence, as well as in vitro, in vivo and clinical findings that support the broadly protective potential demonstrated by melatonin.
Acute Illness Associated With Cannabis Use, by Route of Exposure
Authors: Andrew A. Monte, Shelby K. Shelton, Eleanor Mills, Jessica Saben, Andrew Hopkinson, Brandon Sonn, Michael Devivo, Tae Chang, Jacob Fox, Cody Brevik, Kayla Williamson, Diana Abbott
Journal: Annals of Internal Medicine (2019)

Background: Little is known about the relative harms of edible and inhalable cannabis products. Objective: To describe and compare adult emergency department (ED) visits related to edible and inhaled cannabis exposure. Design: Chart review of ED visits between 1 January 2012 and 31 December 2016. Setting: A large urban academic hospital in Colorado. Participants: Adults with ED visits with a cannabis-related International Classification of Diseases, Ninth or 10th Revision, Clinical Modification (ICD-9-CM or ICD-10-CM), code. Measurements: Patient demographic characteristics, route of exposure, dose, symptoms, length of stay, disposition, discharge diagnoses, and attribution of visit to cannabis. Results: There were 9973 visits with an ICD-9-CM or ICD-10-CM code for cannabis use. Of these, 2567 (25.7%) visits were at least partially attributable to cannabis, and 238 of those (9.3%) were related to edible cannabis. Visits attributable to inhaled cannabis were more likely to be for cannabinoid hyperemesis syndrome (18.0% vs. 8.4%), and visits attributable to edible cannabis were more likely to be due to acute psychiatric symptoms (18.0% vs. 10.9%), intoxication (48% vs. 28%), and cardiovascular symptoms (8.0% vs. 3.1%). Edible products accounted for 10.7% of cannabis-attributable visits between 2014 and 2016 but represented only 0.32% of total cannabis sales in Colorado (in kilograms of tetrahydrocannabinol) during that period. Limitation: Retrospective study design, single academic center, self-reported exposure data, and limited availability of dose data. Conclusion: Visits attributable to inhaled cannabis are more frequent than those attributable to edible cannabis, although the latter is associated with more acute psychiatric visits and more ED visits than expected. Primary Funding Source: Colorado Department of Public Health and Environment.