tbuckley/cabot-search huggingface dataset:
Abstract 17074: Methadone Potently Blocks Cardiac IK1 Leading to Membrane Instability
Authors: Michael Klein, Robert Geiger, Mori J Krantz, Robert Goldstein, Thomas P Flagg, Mark C HAIGNEY
Journal: Circulation (2020)

Introduction: Methadone is the second most frequently reported cause of drug-induced cardiac arrest in pharmacovigilance databases, yet the mechanism of its pro-arrhythmia is unclear. Methadone-induced QTU wave prolongation has been repeatedly observed and attributed to inhibition of the delayed rectifier hERG current, but QTU fusion suggests the inwardly rectifying K + current (IK1) might also be affected by methadone. Hypothesis: Methadone pro-arrhythmia is associated with potent block of the IK1 current responsible for rapid terminal repolarization of the cardiac action potential (AP). Methods: Human Kir2.2, encoding the IK1 current, was transiently expressed in COS cells. hERG1a was stably expressed in CHO cells. Cardiac myocytes from swine were obtained by ventricular enzymatic dissociation. Ionic current and APs were measured using patch-clamp methods. Methadone HCl (R+S racemates) was dissolved in Tyrode solution. Results: Methadone suppressed IK1 current with an IC 50 of 1.47 uM (Fig 1A). Methadone also suppressed outward IK1 (-60 mV) measured in swine myocytes (Ba 2+ -sensitive current) with an IC 50 of 1.52 μM. Methadone suppressed hERG currents with an IC 50 of 2.1 μM. APs measured in swine myocytes exhibited significant prolongation (13 ± 4 % increase of APD 90 , p&lt;0.029, n=7) as well as slowing of the rate of terminal repolarization (a specific marker of IK1 blockade) in the presence of 1 μM methadone (Fig. 1B). Fluctuations of diastolic voltage increased by 30 ± 12 and 151 ± 27 % (n=3; p&lt;0.04) in 0.1 and 1 μM methadone, respectively, consistent with a reduction in membrane stability. Conclusions: Methadone is an equipotent blocker of IK1 and hERG. The effect of IK1 block coupled with modest hERG block has a synergistic effect on terminal repolarization that may partially explain the pro-arrhythmic impact of methadone. Moreover, this observation may be generalized to other drugs where unsuspected IK1 blockade may contribute to pro-arrhythmia and torsade de pointes.
HEPATIC STEATOSIS IS ASSOCIATED WITH ELEVATED ALANINE AMINOTRANSFERASE (ALT) BUT NOT ELEVATED BILIRUBIN OR HEPATIC DECOMPENSATION IN PATIENTS WITH NOVEL CORONAVIRUS DISEASE 2019 (COVID-19)
Authors: I. A. Kassab, F. Hawa, J. A. Berinstein, C. A. Steiner, K. D. Platt, J. Louissaint, C. Y. Hsu, C. A. Reddy, N. T. Gunaratnam, V. Chen, P. Sharma
Journal: Hepatology (2020)

Background: Novel coronavirus disease 2019 (COVID-19) is a global pandemic with significant morbidity and mortality  Possible association between non-alcoholic fatty liver disease (NAFLD) and worse COVID-19 disease progression has been suggested but not well described in the United States We investigated whether COVID-19 was associated with elevations in liver enzymes or hepatic decompensation in patients with underlying hepatic steatosis Methods: We retrospectively reviewed the charts of consecutive adults treated at the University of Michigan for COVID-19 between March 1 and April 30, 2020  Hepatic steatosis was defined based on imaging >30 days prior to COVID-19 diagnosis  Outcomes were: (1) peak ALT or bilirubin following COVID-19 diagnosis, (2) ALT >2 or 5 times upper limit of normal (ULN), defined as the higher of baseline ALT or 19 U/L in women and 30 U/L in men, and (3) jaundice defined as bilirubin >2 or 4 mg/dl We conducted regressions with the above outcomes as dependent variables and hepatic steatosis as the primary predictor These regression models were logistic for outcomes of abnormal ALT or bilirubin and linear for maximal ALT or bilirubin Results: Evidence of steatosis on prior imaging was found in 80/159 (50 3%) patients Overall, 89% of patients were hospitalized, 51% were admitted to intensive care unit, and 16% died Chronic liver disease other than NAFLD was found in 14% of patients, 5% had cirrhosis, and 2 7% had prior liver decompensation with ascites, variceal bleeding, or hepatic encephalopathy Patients with steatosis were younger, more often African-American with higher body mass index than those without steatosis Baseline ALT and total bilirubin were higher in the steatosis group Hepatic steatosis was associated with higher incidence of ALT >2x ULN (OR 2 93 [1 23-6 97]) or >5x ULN (OR 6 21 [1 45-26 62]), and with peak ALT (beta 39 7 [7 85-71 49]) Hepatic steatosis was not associated with increased bilirubin Rates of liver decompensation were very low: 1 3% and 2 5%, respectively, with no difference based on NAFLD status (p > 0 4 for both) (Table 1) Conclusion: Analysis from our cohort showed that NALFD is associated with acute hepatocellular injury in patients with COVID-19 Strengths of this study include granularity of data available for review Weaknesses include the observational and single-center nature of the study Larger scale multi-center studies are needed to corroborate these findings (Table Presented)
Abstract 19339: The Establishment of Tumorigenicity Assay Promise the Safety in the Cardiomyogenesis Therapy Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Clinical Application
Authors: Emiko Ito, Shigeru Miyagawa, Satsuki Fukushima, Ai Kawamura, Maki Takeda, Akima Harada, Nagako Sougawa, Hiroko Iseoka, Motoko Shiozaki, Noriko Mochizuki-oda, Atsuhiro Saito, Yoji Sato, Yoshiki Sawa
Journal: Circulation (2017)

Background: Although transplantation of human induced pluripotent stem cells derived cardiomyocytes (hiPSCs-CMs) have a possibility of treatment for heart failure, potential tumorigenicity is major...
Self-assembling A6K peptide nanotubes as a mercaptoundecahydrododecaborate (BSH) delivery system for boron neutron capture therapy (BNCT)
Authors: Hiroyuki Michiue, Mizuki Kitamatsu, Asami Fukunaga, Nobushige Tsuboi, Atsushi Fujimura, Hiroaki Matsushita, Kazuyo Igawa, Tomonari Kasai, Natsuko Kondo, Hideki Matsui, Shuichi Furuya
Journal: Journal of Controlled Release (2020)

Boron neutron capture therapy (BNCT) is a tumor selective therapy, the effectiveness of which depends on sufficient 10B delivery to and accumulation in tumors. In this study, we used self-assembling A6K peptide nanotubes as boron carriers and prepared new boron agents by simple mixing of A6K and BSH. BSH has been used to treat malignant glioma patients in clinical trials and its drug safety and availability have been confirmed; however, its contribution to BNCT efficacy is low. A6K nanotube delivery improved two major limitations of BSH, including absence of intracellular transduction and non-specific drug delivery to tumor tissue. Varying the A6K peptide and BSH mixture ratio produced materials with different morphologies-determined by electron microscopy-and intracellular transduction efficiencies. We investigated the A6K/BSH 1:10 mixture ratio and found high intracellular boron uptake with no toxicity. Microscopy observation showed intracellular localization of A6K/BSH in the perinuclear region and endosome in human glioma cells. The intracellular boron concentration using A6K/BSH was almost 10 times higher than that of BSH. The systematic administration of A6K/BSH via mouse tail vein showed tumor specific accumulation in a mouse brain tumor model with immunohistochemistry and pharmacokinetic study. Neutron irradiation of glioma cells treated with A6K/BSH showed the inhibition of cell proliferation in a colony formation assay. Boron delivery using A6K peptide provides a unique and simple strategy for next generation BNCT drugs.
Endoscopic retrieval of a huge gastric trichobezoar using an electrosurgical knife
Authors: Seung Gyun Baek, Chi Hyuk Oh, Ga Young Shin, Jung-Wook Kim, Jae-Young Jang
Journal: Endoscopy (2020)

A trichobezoar is a rare type of bezoar and usually located in the stomach; however, sometimes it extends through the pylorus into the small bowel, even reaching the transverse colon [1]. Trichobezoars may cause potentially life-threatening complications, such as intestinal obstruction, gastric bleeding, and perforation. Epigastric surgical incision is the most common method of large trichobezoar removal [2]. Herein, we report a case of successful endoscopic retrieval of a trichobezoar after its fragmentation using an electrosurgical knife.
Judge rules that GP suspended for excessive prescribing must be struck off
Authors: Clare Dyer
Journal: BMJ (2020)

A GP who was suspended from the UK medical register for 12 months has now been struck off by a High Court judge after a successful appeal by the Professional Standards Authority for Health and Social Care.1

Mrs Justice Farbey ruled that a medical practitioners tribunal, which decided not to erase David Dighton from the register in October 2019, had reached an “unreasonable” conclusion and that its reasoning was “flawed.”

Dighton, who trained in cardiology and worked in academic medicine before becoming a sole practitioner at a private practice in Essex in …
Review of Artificial Intelligence Techniques in Imaging Data Acquisition, Segmentation, and Diagnosis for COVID-19
Authors: Feng Shi, Jun Wang, Jun Shi, Ziyan Wu, Qian Wang, Zhenyu Tang, Kelei He, Yinghuan Shi, Dinggang Shen
Journal: IEEE Reviews in Biomedical Engineering (2020)

The pandemic of coronavirus disease 2019 (COVID-19) is spreading all over the world. Medical imaging such as X-ray and computed tomography (CT) plays an essential role in the global fight against COVID-19, whereas the recently emerging artificial intelligence (AI) technologies further strengthen the power of the imaging tools and help medical specialists. We hereby review the rapid responses in the community of medical imaging (empowered by AI) toward COVID-19. For example, AI-empowered image acquisition can significantly help automate the scanning procedure and also reshape the workflow with minimal contact to patients, providing the best protection to the imaging technicians. Also, AI can improve work efficiency by accurate delineation of infections in X-ray and CT images, facilitating subsequent quantification. Moreover, the computer-aided platforms help radiologists make clinical decisions, i.e., for disease diagnosis, tracking, and prognosis. In this review paper, we thus cover the entire pipeline of medical imaging and analysis techniques involved with COVID-19, including image acquisition, segmentation, diagnosis, and follow-up. We particularly focus on the integration of AI with X-ray and CT, both of which are widely used in the frontline hospitals, in order to depict the latest progress of medical imaging and radiology fighting against COVID-19.
Abstract 16918: COVID-19 Associated Acute Myocardial Injury With Prolonged Troponin Elevation
Authors: Ly Tran, Charlie Ervin, Mathew J Thomas, David Moore, Rahul Sampath, Steve Isserman
Journal: Circulation (2020)

Introduction: Acute myocardial injury in the setting of COVID-19 has been well described and is associated with higher mortality. Hypothesis: Myocarditis has been reported as a rare cause of myocardial injury in at least seven recent case reports. Methods: A 70-year-old man with coronary artery disease status post bypass surgery with recent hospitalization for left shoulder septic arthritis with MSSA bacteremia was readmitted 10 days later with a positive PCR test for SARS-CoV-2 at a local nursing facility. His symptoms were dyspnea, chest pain, fever, nausea, and diarrhea. Previous hospitalization he underwent evaluation for chest pain with cardiac catheterization revealing ejection fraction (EF) of 45% and patency of all three grafts. Results: Laboratory investigation showed elevated markers of myocardial injury with high sensitivity troponin I (hs-TnI) of 17,643 ng/L and B-type natriuretic peptide of 2,627 pg/mL, elevated C-Reactive Protein, D-dimer, and sedimentation rate. Chest X-ray showed hazy opacity in the infrahilar right lung. ECG notable for a first degree AV block with no ST-segment elevation. Transthoracic echocardiogram (TTE) showed an EF of 20% with global left ventricular dysfunction with hypokinesis of the right ventricle. No evidence of pericardial effusion. Blood cultures were negative. Management of heart failure led to clinical improvement. Over the next three months, Hs-TnI level stayed elevated at 11,339 ng/L for four weeks and trended down to 6,791 ng/L. The patient was seropositive for COVID-19 IgG eight weeks after the diagnosis of COVID-19 was made. Conclusions: We report the first case of COVID-19 related myocardial injury with prolonged and extreme troponin elevation. Recent favorable cardiac catheterization further supports immune mediated myocarditis over ischemic cardiomyopathy. Unfortunately, no endomyocardial biopsy has been performed.
Abstract 14550: Sex Differences on Time-dependent Changes in Brain-type Natriuretic Peptide Among Patients With Hypertrophic Cardiomyopathy
Authors: Nobuyuki Enzan, Shouji Matsushima, Tomomi Ide, Hidetaka Kaku, Takeshi Tohyama, Kouta Funakoshi, Taiki Higo, Hiroyuki Tsutsui
Journal: Circulation (2020)

Introduction: Sex differences in biomarkers such as brain-type natriuretic peptide (BNP) have not been fully elucidated among patients with hypertrophic cardiomyopathy (HCM). Hypothesis: Sex affects transition of BNP concentration among patients with HCM. Methods: This retrospective cohort study analyzed clinical personal record of HCM, a national database of Japanese Ministry of Health, Labor and Welfare, between 2009 and 2014. This record annually collected HCM patient data. Patients with HCM who were assessed with BNP concentration both at baseline and 2-year follow-up were included. Patients were excluded if they received ventricular assist device or heart transplantation during follow-up period. Outcomes were assessed according to sex. The primary endpoint was BNP concentration at 2-year follow-up. The log-transformed BNP concentration at 2-year was analyzed by analysis of covariance adjusted for baseline characteristics including baseline BNP. The cubic spline analysis of BNP concentration at 2-year for sex by BNP concentration was performed. Results: Out of 3,570 patients enrolled in the clinical personal record of HCM, 611 patients were included in the present analysis. Mean age was 60.4 years and female and male were 254 (41.6%) and 357 (58.4%), respectively. Left ventricular (LV) ejection fraction was higher in female (64.7 ± 14.5 vs. 61.4 ± 16.0%, P =.012), LV diastolic diameter (43.4 ± 7.8 vs. 48.0 ± 8.0 mm, P &lt;.001), LV systolic diameter (27.3 ± 8.9 vs. 31.2 ± 9.0 mm, P &lt;.001), posterior wall thickness (11.2 ± 3.0 vs. 11.9 ± 3.8 mm, P =.011), and left atrial diameter (41.8 ± 8.8 vs. 45.8 ± 10.1 mm, P &lt;.001) were smaller in female. Baseline BNP concentration was higher in female (320.3 [159.0-583.1] vs. 182.8 [86.1-363.9], P &amp;lt;.001). Female sex was associated with higher log-transformed BNP at 2-year in both complete case analysis (coefficient 0.31; 95% confidence interval [CI] 0.13-0.48; P &lt;.001) and multiple imputation analysis (coefficient 0.63: 95% CI 0.44-0.82; P &lt;.001). Cubic spline analysis showed that female sex was associated with higher BNP concentration at 2-year irrespective of baseline BNP concentration. Conclusions: Female sex was associated with higher BNP levels at 2-year follow-up compared with male sex in HCM.
Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation
Authors: Cristina Tecchio, Marco Antonio Cassatella
Journal: Cellular and Molecular Immunology (2020)

Abstract Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a life-saving procedure used for the treatment of selected hematological malignancies, inborn errors of metabolism, and bone marrow failures. The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection. However, recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions. Accordingly, neutrophils are emerging as highly versatile cells that are able to acquire different, often opposite, functional capacities depending on the microenvironment and their differentiation status. Herein, we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT, from the hematopoietic stem cell (HSC) mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion. We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versus-host disease (GVHD) prophylaxis. Finally, the potential involvement of neutrophils in alloHSCT-related complications, such as transplant-associated thrombotic microangiopathy (TA-TMA), acute and chronic GVHD, and cytomegalovirus (CMV) reactivation, is also discussed. Based on the data reviewed herein, the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role. However, much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT.
Cellular context of IL-33 expression dictates impact on anti-helminth immunity
Authors: Li-Yin Hung, Yukinori Tanaka, Karl Herbine, Christopher Pastore, Brenal Singh, Annabel Ferguson, Nisha Vora, Bonnie Douglas, Kelly Zullo, Edward M. Behrens, Tiffany Li Hui Tan, Michael A. Kohanski, Paul Bryce, Cailu Lin, Taku Kambayashi, Danielle R. Reed, Breann L. Brown, Noam A. Cohen, De’Broski R. Herbert
Journal: Science Immunology (2020)

The pore-forming protein perforin-2 facilitates IL-33 release from dendritic cells.
Abstract IA-10: Overcoming the seven deadly hallmarks of pancreatic cancer
Authors: David Tuveson
Journal: Cancer Research (2020)

Abstract Pancreatic cancer remains highly lethal, however recent insights regarding disease pathogenesis coupled with the emergence of new diagnostic methods and therapeutic agents engender a more hopeful outlook. We delineate 7 common characteristics of pancreatic cancer including desmoplastic stroma, dysregulated metabolism, chronic inflammation, undruggable KRAS, early metastasis, diagnostic deficiencies, and rapid deconditioning and posit that these hallmarks are collectively responsible for disease aggressiveness and clinical failure. Finally, we propose a strategic framework to address these challenges and thereby improve patient outcomes. Citation Format: David Tuveson. Overcoming the seven deadly hallmarks of pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr IA-10.
Abstract 16269: Does the “July Effect” Impact Heart Failure Outcomes? A Real-World Analysis of More Than Half a Million Nationwide Admissions
Authors: Ahmed A Kolkailah, Marwan Abougergi, Parth V Desai, Axi Patel, Setri Fugar, Alexis K Okoh, Ahmed Al-ogaili, Sameer Hirji, Tsuyoshi Kaneko, Annabelle S Volgman, Rami Doukky
Journal: Circulation (2020)

Background: The “July effect” is a well-described phenomenon in academic medicine, relating to the annual influx of new trainees. We examined whether the “July effect” impacts inpatient outcomes of admissions for heart failure (HF). Methods: Between 2012 and 2014, we included adult patients (≥18 years) with a primary diagnosis of HF, defined using ICD-9 codes, from the National Inpatient Sample. We excluded non-teaching hospitals. Primary endpoint was in-hospital mortality. Secondary endpoints included hospital length of stay (LOS) and total cost adjusted for inflation. Logistic regression and adjusted odds ratio (OR) were used to adjust for confounders. Based on academic calendar, we classified admissions into 4 quarters (Q1-4). Q1 and Q4 were designated to assess the effect of novice (July effect) vs. seasoned trainees, respectively. Results: We identified 699,675 HF admissions during Q1 and Q4 over the study period. Mean age was 71 years and 48% were females. There were 20,270 in-hospital deaths (Q1 9,695 vs. Q4 10,575). After adjusting for confounders, there was no mortality difference between Q1 and Q4 admissions; adjusted OR 0.96, p = 0.23 (Figure). Similarly, there was no difference in hospital LOS or total cost; 5.8 vs. 5.8 days, p = 0.66 and $13,755 vs. $13,586, p = 0.46, in Q1 and Q4, respectively. Conclusion: In the largest study to date, there was no evidence of a “July effect” on inpatient HF outcomes. This may be credited to the well-defined guidelines which facilitate safe patient care in these patients.
Abstract 14210: Comparison of Two Recent Ceramide-based Coronary Risk Prediction Scores: CERT and CERT-2
Authors: Andreas Leiherer, Axel Muendlein, Christoph H Saely, Reijo Laaksonen, Mitja Laaperi, Alexander Vonbank, Peter Fraunberger, Heinz Drexel
Journal: Circulation (2020)

Introduction: The Coronary Event Risk Test (CERT) is a validated cardiovascular risk predictor that uses circulating ceramide concentrations to allocate patients into one of four risk categories. This test has recently been updated (CERT-2), now additionally including phosphatidylcholine concentrations. Hypothesis: We hypothesize that CERT and CERT-2 have the power to predict cardiovascular mortality in patients with cardiovascular disease (CVD). Methods: We investigated a patient cohort of 999 patients with established CVD. Results: Overall, comparing survival curves (figure) for over 12 years of follow up and the predictive power of survival models using net reclassification improvement (NRI), CERT-2 was the best predictor of cardiovascular mortality, surpassing CERT (NRI=0.456; p=0.01) and also the 2019 ESC-SCORE (NRI=0.163; p=0.04). Patients in the highest risk category of CERT as compared to the lowest category had a HR of 3.63 [2.09-6.30] for cardiovascular death; for CERT-2 the corresponding HR was 6.02 [2.47-14.64]. Among patients with T2DM (n=322), the HR for cardiovascular death was 3.00 [1.44-6.23] using CERT and 7.06 [1.64-30.50] using CERT-2; the corresponding HRs among non-diabetic subjects were 2.99 [1.20-7.46] and 3.43 [1.03-11.43], respectively. Conclusions: We conclude that both, CERT and CERT-2 scores are powerful predictors of cardiovascular mortality in CVD patients, especially in those patients with T2D, performance is even higher with CERT-2.