tbuckley/cabot-search huggingface dataset:
IMPACT OF HISTORY OF CHRONIC VIRAL HEPATITIS AND LIVER FIBROSIS ON RISK OF HOSPITALIZATION AND DEATH AMONG PATIENTS WITH SARS-COV-2 INFECTION
Authors: Mei Lu, Loralee B Rupp, J A Boscarino, M A Schmidt, Y Daida, Yueren Zhou, Sheri Trudeau, Jia Li, Stuart C Gordon
Journal: Hepatology (2020)

Background: We investigated factors associated with Covid-19 related hospitalization and death among patients with and without a history of chronic viral hepatitis B or C (CHB/CHC) in a single large, integrated health system located in metropolitan Detroit, Michigan, an area that experienced a significant outbreak of SARS-Cov-2 in Spring 2020  Methods: Baseline data were collected before date of first positive SARS-CoV-2 test or Covid-related hospitalization, whichever was earlier Risk of hospitalization was analyzed with logistic regression;risk of death with Cox regression Variables with p-values <0 05 were retained in the final multivariable models Results: Of 6661 patients that tested SARS-CoV-2 positive from March 12-April 26, 2020, 94 (1 4%) had a history of CHB or CHC A total of 2604 were hospitalized due to Covid-19, 55 (58 5%) with CHB or CHC and 2549 (38 8%) without CHB/CHC Among hospitalized patients, 10 (18 2%) CHB/CHC patients and 426 (16 7%) non-hepatitis patients died In multivariable analyses, viral hepatitis was not a risk factor for hospitalization, but approached significance for death (adjusted Hazard Ratio [aHR] 1 82, 95% Confidence Interval [CI] 0 96-3 46) In addition to recognized risk factors for Covid-19 severity such as increasing age, obesity, type 2 diabetes, and multiple co-morbidities, we found that increasing Fibrosis-4 (FIB4) score (a biomarker for liver fibrosis and cirrhosis) was associated with risk of hospitalization (adjusted Odds Ratio [aOR] 95%CI 1 32, 1 16-1 51) African American and male patients were also at higher risk of hospitalization Notably, a number of risk factors for hospitalization were not associated with or were associated with reduced risk of death among hospitalized patients;African American patients and those with BMI ≥30 had lower mortality than White patients and those with BMI <25 (aHR 0 73, 95%CI 0 60-0 89;and aHR 0 69, 95%CI 0 54-0 88) respectively Conclusion: Increasing baseline FIB4 index is associated with higher risk of hospitalization among patients with Covid-19 History of CHB or CHC trended toward increased risk of Covid-related mortality;future studies in larger samples of patients with chronic viral hepatitis are warranted
Eating disorder services in England need urgent changes, says coroner
Authors: Clare Dyer
Journal: BMJ (2020)

A coroner has called for urgent changes to eating disorder services nationwide after concluding that a 19 year old student with anorexia nervosa died because of gross and systemic NHS failures and neglect.

The assistant coroner for Cambridgeshire, Sean Horstead, said that Averil Hart’s death in December 2012 could have been avoided and was partly caused by neglect.

Hart, a creative writing student, started her first term at the University of East Anglia in September 2012. She had a three year history of anorexia and had been discharged from the eating disorder unit at Addenbrooke’s Hospital the previous month after an 11 month stay.

She was found collapsed in her room on 7 December and was taken to Norfolk and Norwich University …
Crossing Boundaries—Violation or Obligation?
Authors: Gordon D. Schiff
Journal: JAMA (2013)

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Abstract 13764: Chronic Electronic Cigarette Vapor Exposure Leads to Impaired Cardiac Function in Experimental Rat Myocardial Ischemia/reperfusion Model
Authors: Wangde Dai, Jianru Shi, Juan Carreno, Lifu Zhao, Michael T Kleinman, David A Herman, Rebecca M Johnson, Samantha Renusch, Irene Hasen, Amanda Ting, Robert A Kloner
Journal: Circulation (2020)

Background: We investigated the effects of long-term electronic cigarettes with nicotine (eC) vaping on cardiac function and structure in rats subjected to myocardial infarction (MI). Methods: After 8 weeks of exposure to either pure air (n=20) or eC (n=20), rats were anesthetized, and were subjected to 30 minutes of coronary artery occlusion followed by 3 hours of reperfusion. Cardiac function was assessed by echocardiogram and pressure measurements of the aorta and left ventricle (LV). Cardiac output (CO) was measured using a thermodilution catheter. At 3 hours of reperfusion, ischemic risk zone, no-reflow and infarct areas were determined. Results: Prior to coronary artery occlusion, chronic eC exposure was associated with a lower CO (45 ± 2 ml/min ) compared to air (55 ± 4 ml/min; p&lt;0.05)) and a decrease in +dP/dt (5226 ± 294 mmHg/s versus 6062 ± 271 mmHg/s; p=0.05). After 30 minutes of coronary occlusion and 2.5 hours of reperfusion, CO and LV + dp/dt fell in both groups, but remained significantly lower in eC compared to the pure air group (Table). LV systolic and diastolic dimensions were significantly smaller in the E-Cig group compared to the air group. Systolic and diastolic anterior LV wall thickness were significantly thicker in the eC group after reperfusion. The ischemic risk size was comparable between the 2 groups. MI size was 48.8 ± 4.8% of the ischemic risk zone in the air group and 45.4 ± 4.4 % in the eC group (p=0.603). The area of no reflow was 26.7 ± 4.0% of the ischemic risk zone in the air group and 21.1 ± 3.5% in the E-C group (p=0.298). Chronic eC exposure did not change heart rate and blood pressure, but the significantly increased the systemic arterial resistance. Conclusions: Chronic exposure to eC significantly impaired cardiac function in rats prior to and during ischemia/reperfusion, increased arterial resistance, but did not increase infarct size or no-reflow zone. Increased LV wall thickness of the risk zone suggested that eC may have increased edema.
Hypoxic burden and heart rate variability predict stroke incidence in sleep apnoea
Authors: Margaux Blanchard, Chloé Gervès-Pinquié, Mathieu Feuilloy, Marc Le Vaillant, Wojciech Trzepizur, Nicole Meslier, François Goupil, Thierry Pigeanne, Frédéric Balusson, Emmanuel Oger, AbdelKebir Sabil, Jean-Marc Girault, Frédéric Gagnadoux
Journal: European Respiratory Journal (2020)

<b>Indices of sleep apnoea-related hypoxic burden and heart rate variability derived from full-night polysomnography might be useful for identifying sleep apnoea patients at risk for stroke</b>https://bit.ly/3eIYVsc
Prevalence of impaired physiological function consistent with Relative Energy Deficiency in Sport (RED-S): an Australian elite and pre-elite cohort
Authors: Margot Anne Rogers, Renee Newcomer Appaneal, David Hughes, Nicole Vlahovich, Gordon Waddington, Louise M Burke, Michael Drew
Journal: British Journal of Sports Medicine (2020)

Objectives Athlete health, training continuity and performance can be impeded as a result of Relative Energy Deficiency in Sport (RED-S). Here we report the point prevalence of symptoms described by the RED-S model in a mixed-sport cohort of Australian female athletes. Methods Elite and pre-elite female athletes (n=112) from eight sports completed validated questionnaires and underwent clinical assessment to assess the point prevalence of RED-S symptoms. Questionnaires included the Depression, Anxiety and Stress Questionnaire (DASS-21), Generalized Anxiety Disorder (GAD-7), Center for Epidemiological Studies Depression Scale (CES-D), SCOFF questionnaire for disordered eating, Low Energy Availability in Females Questionnaire (LEAF-Q), and a custom questionnaire on injury and illness. Clinical assessment comprised resting metabolic rate (RMR) assessment, dual-energy X-ray absorptiometry-derived body composition and bone mineral density, venous and capillary blood samples, and the Mini International Neuropsychiatric Interview (MINI 7.0.2). Descriptive prevalence statistics are presented. Results Almost all (80%) participants (age 19 (range 15–32) years; mass 69.5±10.3 kg; body fat 23.1%±5.0%) demonstrated at least one symptom consistent with RED-S, with 37% exhibiting between two and three symptoms. One participant demonstrated five symptoms. Impaired function of the immunological (28%, n = 27), haematological (31%, n = 33) and gastrointestinal (47%, n = 51) systems were most prevalent. A moderate to high (11%–55%) prevalence of risk of low energy availability was identified via RMR and LEAF-Q, and identified mental illnesses were prevalent in one-third of the assessed cohort. Conclusion Symptoms described by the RED-S model were prevalent in this cohort, supporting the need for improved awareness, monitoring and management of these symptoms in this population.
Abstract 14935: Targeted Optical Molecular Imaging of Atheroma Calcification Using Novel Aldendronate-based Probe
Authors: Dong Oh Kang, Yong Geun Lim, Joon Woo Song, Ye Hee Park, Hyun Jung Kim, Hyeong Soo Nam, Yeon Hoon Kim, Wang-Yuhl Oh, Hongki Yoo, Kyeongsoon Park, Jin Won Kim
Journal: Circulation (2020)

Background/Objectives: Vascular spotty calcification is an actively regulated biological process resulting in plaque vulnerability. We investigated the feasibility of a novel alendronate-based near-infrared fluorescence (NIRF)-emitting probe to specifically target atherosclerotic calcification in a murine model in vivo using our customized high-resolution multichannel intravital molecular imaging system (IVFM). Methods/Results: We have fabricated a calcium-binding NIRF probe by chemically coupling alendronate, a specific targeting ligand, and NIRF-emitting Cy5.5 to the ends of azide-PEG-NHS ester (Al-Cy5.5). Prepared Al-Cy5.5 has high affinity for calcium phosphate-containing bone minerals. In vitro, Al-Cy5.5 specifically binds to RANKL-induced osteogenic-macrophages as compared to macrophages (p&lt;0.01). On whole body fluorescence imaging to assess time-dependent excretion, NIRF signals remained visible up to 48 hrs. Then, in mice with calcified plaque induced by a combination diet of high-cholesterol and warfarin, Al-Cy5.5 (2.5 mg/kg) was intravenously injected. 48 hrs after administration, murine calcified atheroma was assessed using a customized high-resolution multichannel IVFM, which demonstrated highly enhanced NIRF signals in vivo in the calcified areas of murine carotid plaques (p&lt;0.01, Figure). Ex vivo laser scanning fluorescence microscopic and immune-histological findings from the corresponding sister sections well corroborated the in vivo imaging results, which demonstrated the co-localization of NIRF signals with plaque calcifications (von-Kossa stain). Conclusions: Our novel calcification targeted probe, Al-Cy5.5, was able to selectively target atheroma calcification in vivo in a murine model as assessed by optical IVFM. This novel targetable strategy is expected to provide a promising theranostic basis for calcified high-risk plaques by integration with multimodal customized catheter imaging system.
Abstract 13897: Native T1-mapping by Cardiac MRI as a Biomarker of Remodeling in Boys With Duchenne Muscular Dystrophy
Authors: Seraina A Dual, Nyasha G Maforo, Doff B McElhinney, Ashley Prosper, Holden Wu, Shiraz A Maskatia, Pierangelo Renella, Nancy J Halnon, Daniel Ennis
Journal: Circulation (2020)

Cardiac magnetic resonance (CMR) is an important tool to assess cardiac disease progression in boys with Duchenne muscular dystrophy (DMD), with native (pre-contrast) myocardial T1-mapping considered a possible biomarker of fibrosis. Due to its thin wall and highly trabeculated structure, the right ventricle (RV) remains understudied in DMD despite pre-clinical evidence of RV involvement. After determining the most robust method of obtaining RV-T1, we assessed the hypothesis that RV-T1 distinguishes healthy controls from boys with DMD. Boys with DMD (N=27) and age-matched healthy control boys (N=17) were prospectively enrolled for a 3T CMR exam (Skyra, Siemens). The CMR exam included standard functional imaging, LGE imaging, and native T1 maps acquired at diastasis. Native RV-T1 was evaluated in four regions of interest (ROIs): 1 pixel (px) along the RV centerline, 3px dilated RV centerline, a segment within the RV lateral wall, and the RV inferior wall (Figure 1). Robustness was assessed in controls only and was defined as an acceptable number of pixels, coefficient of variation (COV) per ROI, percentage of readable images, and lowest inter-observer variability across three observers. Subsequently, a t-test assessed the difference between boys with DMD and controls using the most robust RV ROI. Comparing the four ROIs, we found an average size of the ROI of 65, 196, 23, 25 px; a COV of 13.4%, 16.6%, 6.0%, 9.9%; and 75%, 75%, 93%, 81% of readable images. Intra-class correlation (0.75) was highest and both mean bias (20ms) and limits of agreement (100ms) were lowest for the RV 1px ROI. Using the 1px ROI, the RV-T1 was higher and more variable in boys with DMD compared to controls (1526 [1457,1650] ms vs. 1432 [1390,1486] ms; p&lt;0.0001). Native RV-T1 is elevated in boys with DMD, if measured along a 1px centerline ROI. The methods described herein may enable using native RV-T1 as a biomarker of fibrosis in DMD and other pathologies. Correlation with functional indices is pending.
<i>QuickStats:</i> Percentage* of Currently Employed Adults Aged ≥18 Years Who Reported an Average of ≤6 Hours of Sleep<sup>†</sup> per 24-Hour Period, by Employment Category<sup>§</sup> — National Health Interview Survey, United States, 2008–2009 and 2017–2018<sup>¶</sup>
Journal: MMWR Morbidity and Mortality Weekly Report (2020)
Abstract PO-035: Overcoming adaptive resistance to mutant KRAS and MEK inhibitors by co-targeting mTORC1/2 in pancreatic cancer
Authors: Wells Brown, Paul McDonald, Shoukat Dedhar
Journal: Cancer Research (2020)

Abstract Activating KRAS mutations are found in over 90% of pancreatic ductal adenocarcinomas (PDAC), yet KRAS has remained a difficult target to inhibit pharmacologically. While mutant KRAS-specific inhibitors have recently been developed, there is increasing awareness that adaptive resistance to these inhibitors limits their efficacy as single agents. Here, we demonstrate, using several human and mouse models of PDAC, rapid acquisition of tumor resistance in response to genetic or pharmacologic targeting of KRAS or MEK, associated with increased phosphorylation of Akt and Rictor, in an ILK-dependent manner. While pharmacologic inhibition ofmTORC1/2 results in a compensatory increase in ERK phosphorylation, combinatorial treatment of PDAC cells with either KRAS or MEK inhibitors together with mTORC1/2 inhibitors results in synergistic cytotoxicity and cell death reflected by sustained inhibition of p-ERK and p-Rictor/p-Akt, and of downstream regulators of protein synthesis and cell survival. Importantly, relative to single agents alone, this combination leads to significant inhibition of tumor growth in vivo, including durable tumor regressions and increased survival. We have identified a highly effective combinatorial treatment strategy, using clinically viable inhibitors, which can be applied to PDAC tumors with different KRAS mutations. Citation Format: Wells Brown, Paul McDonald, Shoukat Dedhar. Overcoming adaptive resistance to mutant KRAS and MEK inhibitors by co-targeting mTORC1/2 in 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 PO-035.
Abstract 16785: Student Abstractors Reduce the Cost of Registry Use Without Compromising Quality
Authors: Nasser Lakkis, Allison P Capetillo, Cherie S Boxberger, Stephanie Chapman
Journal: Circulation (2020)

Introduction: Accurate data abstraction is the cornerstone of successful implementation of Get With The Guidelines-Heart Failure, but abstraction costs are the single largest barrier to participation. Objective: The Heart Failure Abstraction Internship was established to test the efficacy of part-time, graduate students as GWTG-HF abstractors in comparison to a registered nurse using an acceptable Data Element Agreement Rate (DEAR). Methods: The selection criteria for the pilot hospital, Ben Taub Hospital, Houston Texas was: not a GWTG-HF participant; serving diverse populations; administrative and physician support and available supervision for interns. Intern abstractors were recruited and paid as American Heart Association (AHA) employees. For the pilot term, the interns were onboarded as volunteers for the pilot hospital. They met the onboarding requirements of AHA and the pilot institution’s requirements for hospital volunteers. The interns; worked on-site at the pilot institution; were given computer access to EPIC electronic medical records and GWTG-HF; were trained by AHA Quality staff and the pilot hospital Cardiology Program Manager; and abstracted all patients with a primary diagnosis of heart failure from October 2017 to December 2018. An AHA nurse auditor virtually re-abstracted 5 records with the pilot, Cardiology Program Manager. The audit was conducted using the July 2018 Clinical Registry Form (CRF) that was also used during the pilot. Results: The intern abstractors matched the re-abstractor at a DEAR of 86.4% with 340 total elements and 46 mismatches. Conclusions: The hypothesis was proven with a DEAR of 86.4%, suggesting hospitals can be successful participants in GWTG utilizing student abstractors for data collection needs. The median payrate for a nurse abstractor is $24.50 per hour, not including benefits*. The rate for part time employment for the abstraction interns was $10.00 per hour. In addition to financial savings for the pilot organization, the interns worked efficiently as they focused on one task allowing the clinical team to focus on process improvement based on the data collected. This PI focus led to other outcome improvements including reduced readmission and increased compliance with GDMT. *Payscale.com
Abstract 14200: Prognostic Significance of Dipstick Proteinuria in Heart Failure With Preserved Ejection Fraction - Insight From the Pursuit-hfpef Registry
Authors: Bolrathanak Oeun, Shungo Hikoso, Daisaku Nakatani, Hiroya Mizuno, Tetsuhisa Kitamura, Katsuki Okada, Tomoharu Dohi, Yohei Sotomi, Hirota Kida, Akihiro Sunaga, Taiki Sato, Takahisa Yamada, Yoshio Yasumura, Akito Nakagawa, Yusuke Nakagawa, Shunsuke Tamaki, Takaharu Hayashi, Masamichi Yano, Yasushi Sakata
Journal: Circulation (2020)

Introduction: Although albuminuria evaluated with urinary albumin-to-creatinine ratio (UACR) was shown to be a prognostic marker in patients with heart failure, measurement of UACR needs special equipment. Urine dipstick test is a simple and convenient method which is available even in community-based health care. Hypothesis: We hypothesized that dipstick proteinuria might be a prognosticator in HFpEF. Methods: We assessed 738 discharged-alive patients in the PURSUIT-HFpEF registry. Patients received urine dipstick test, and were divided into 2 groups according to the absence or presence of proteinuria (proteinuria trace or more). The study endpoint was a composite of all-cause mortality and HF hospitalization. Results: Median age was 82 years and 410 patients were female. Four hundred thirty-four patients: proteinuria-(group 1); 304 patients: proteinuria+(group 2). Group 2 was more likely male with higher frequency of diabetes, previous myocardial infarction and chronic kidney disease, but less likely to take ACEIs than group 1. Higher blood pressure, NT-proBNP, creatinine, E/e’, TRPG, and LV mass index were observed in group 2 than group 1. The composite endpoint and HF hospitalization occurred more often in group 2 than group 1 (HR: 1.43, 95%CI: 1.09-1.87, log-rank P=0.009; HR: 1.57, 95%CI: 1.14-2.15, log-rank P=0.005, respectively); but all-cause mortality did not (HR: 1.40, 95%CI: 0.92-2.11, log-rank P=0.113). Multivariable Cox regression adjusting for NT-proBNP, eGFR and other major confounding factors showed that proteinuria was associated with the composite endpoint (HR: 1.42, 95% CI: 1.05-1.94, P=0.026), and HF hospitalization (HR: 1.51, 95%CI: 1.04-2.18, P=0.030), but not with all-cause mortality (HR: 1.51, 95%CI:0.94-2.43, P=0.092). Conclusions: Dipstick proteinuria may be a prognostic marker in patients with HFpEF. Evaluation of proteinuria by urine dipstick test may be a simple but useful method for risk stratification in HFpEF.
Abstract 16401: Duration of Dual Antiplatelet Therapy in Coronary Heart Disease: A 60,000-patient Meta-analysis of Randomised Controlled Trials
Authors: Anda Bularga, Mohammed Meah, Dimitrios Doudesis, Anoop S Shah, Nicholas L Mills, Kuan Ken Lee, David E Newby
Journal: Circulation (2020)

Introduction: Dual antiplatelet therapy (DAPT) is the cornerstone of pharmacological treatment for patients with acute coronary syndrome (ACS) and in those undergoing percutaneous coronary intervention for stable coronary disease. Despite widespread use, the optimal duration of DAPT remains uncertain. We present an updated meta-analysis comparing outcomes in short-term DAPT (≤ 6 months) versus long-term DAPT (≥ 12 months). Methods: Four major databases were searched for randomised controlled trials of interest. The primary outcome was all-cause mortality. Secondary safety outcomes included any bleeding and major bleeding. Efficacy outcomes included cardiovascular death, myocardial infarction, stent thrombosis, coronary revascularization and thrombotic stroke. Further subgroup analysis stratified by index presentation and a sensitivity analysis to evaluate shorter duration DAPT (≤3 months) was performed. Results: Nineteen randomised controlled trials were included (n=60,879) of which 8 compared shorter duration DAPT (≤3 months) with standard duration (12 months) (n=38,036). Short-term DAPT was associated with an apparent modest increase in myocardial infarction (risk ratio [RR] 1.09; 95% confidence interval [CI], 0.98-1.22) with a major reduction in bleeding (RR 0.68; 95% CI, 0.55-0.83) for major bleeding and (RR 0.66; 95% CI, 0.56-0.77 for any bleeding) and an overall apparent reduction in all-cause mortality (RR 0.90; 95% CI 0.81-1.01). These associations persisted when comparing shorter duration DAPT to standard duration. Subgroup analysis of patients with stable disease or ACS identified no significant heterogenicity in efficacy, safety or mortality outcomes. Conclusion: In the largest meta-analysis to date comparing duration of DAPT, we show that short (≤ 6 months) and shorter (≤ 3 months) DAPT is associated with continuing trends for small reductions in all-cause mortality irrespective of index presentation.