tbuckley/cabot-search huggingface dataset:
Abstract 16343: Sarpogrelate, a Selective Serotonin <sub>2a</sub> Receptor Antagonist, Suppresses Pressure Overlaod-induced Cardiac Hypertrophy and Systolic Dysfunction Through Inhibiting Erk1/2/gata4 Pathway
Authors: Kana Shimizu, Masafumi Funamoto, Yoichi Sunagawa, Yasufumi Katanasaka, Yusuke Miyazaki, Noriyuki Murai, Hiroki Honda, Yoshiki Kawakami, Satoshi Shimizu, nurmila sari, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
Journal: Circulation (2020)

Introduction: Serotonin (5-HT), a neurohormone involved in a wide range of physiological functions, has generated much interest in recent years regarding its potential role in cardiac function. It is reported that sarpogrelate, a selective 5-HT2A receptor antagonist, possesses cardioprotective effect against myocardial infarction, however, the precise molecular mechanism of the effect is still unclear. In this study, we examined the effect of sarpogrelate on pressure overload-induced development of heart failure, another heart failure model. Methods: First, primary cultured cardiomyocytes were treated with 1 μM sarpogrelate and then stimulated with various hypertrophic stimuli. Cardiomyocytes were stained with anti-actinin antibody and the surface area of the cells were measured. The phosphorylation levels of ERK1/2 and GATA4 were assessed by western blotting. Next, C57BL/6j male mice were subjected to a transverse aortic constriction (TAC) and sham operation. One day after the operation, the mice were randomly divided into 3 groups: sarpogrelate at 1 mg/kg or 5 mg/kg, and vehicle as a control. Daily oral administration was repeated for 8 weeks. Results: Sarpogrelate significantly suppressed an increase in the surface area of cardiomyocytes induced not only by 5-HT, but also by phenylephrine, angiotensin II and ET-1. Sarpogrelate suppressed phenylephrine-induced phosphorylation of ERK1/2 and GATA4. In a mice model of heart failure, echocardiographic analysis showed that 5 mg/kg sarpogrelate significantly prevented a TAC-induced increase in posterior left ventricular wall thickness and a decrease in fractional shortening at 8 weeks after the operation. One mg/kg sarpogrelate also suppressed TAC-induced increase in HW/BW ratio, myocardial cell diameter and the mRNA levels of ANF and BNP. Moreover, 1 mg/kg sarpogrelate significantly suppressed TAC-induced phosphorylation of ERK1/2. Conclusions: These results indicate that sarpogrelate significantly suppresses cardiomyocyte hypertrophy and the development of heart failure via at least, in part, by inhibition of ERK1/2/GATA4 pathway. These findings suggest that sarpogrelate may be an effective agent for heart failure therapy.
The impact of voluntary front-of-pack nutrition labelling on packaged food reformulation: A difference-in-differences analysis of the Australasian Health Star Rating scheme
Authors: Laxman Bablani, Cliona Ni Mhurchu, Bruce Neal, Christopher L. Skeels, Kevin E. Staub, Tony Blakely
Journal: PLoS Medicine (2020)

Background Front-of-pack nutrition labelling (FoPL) of packaged foods can promote healthier diets. Australia and New Zealand (NZ) adopted the voluntary Health Star Rating (HSR) scheme in 2014. We studied the impact of voluntary adoption of HSR on food reformulation relative to unlabelled foods and examined differential impacts for more-versus-less healthy foods. Methods and findings Annual nutrition information panel data were collected for nonseasonal packaged foods sold in major supermarkets in Auckland from 2013 to 2019 and in Sydney from 2014 to 2018. The analysis sample covered 58,905 unique products over 14 major food groups. We used a difference-in-differences design to estimate reformulation associated with HSR adoption. Healthier products adopted HSR more than unhealthy products: &gt;35% of products that achieved 4 or more stars displayed the label compared to &lt;15% of products that achieved 2 stars or less. Products that adopted HSR were 6.5% and 10.7% more likely to increase their rating by ≥0.5 stars in Australia and NZ, respectively. Labelled products showed a −4.0% [95% confidence interval (CI): −6.4% to −1.7%, p = 0.001] relative decline in sodium content in NZ, and there was a −1.4% [95% CI: −2.7% to −0.0%, p = 0.045] sodium change in Australia. HSR adoption was associated with a −2.3% [−3.7% to −0.9%, p = 0.001] change in sugar content in NZ and a statistically insignificant −1.1% [−2.3% to 0.1%, p = 0.061] difference in Australia. Initially unhealthy products showed larger reformulation effects when adopting HSR than healthier products. No evidence of a change in protein or saturated fat content was observed. A limitation of our study is that results are not sales weighted. Thus, it is not able to assess changes in overall nutrient consumption that occur because of HSR-caused reformulation. Also, participation into labelling and reformulation is jointly determined by producers in this observational study, impacting its generalisability to settings with mandatory labelling. Conclusions In this study, we observed that reformulation changes following voluntary HSR labelling are small, but greater for initially unhealthy products. Initially unhealthy foods were, however, less likely to adopt HSR. Our results, therefore, suggest that mandatory labelling has the greatest potential for improving the healthiness of packaged foods.
Development and Validation of a Modified Full Age Spectrum Creatinine-Based Equation to Estimate Glomerular Filtration Rate
Authors: Hans Pottel, Jonas Björk, Marie Courbebaisse, Lionel Couzi, Natalie Ebert, Björn O. Eriksen, R. Neil Dalton, Laurence Dubourg, François Gaillard, Cyril Garrouste, Anders Grubb, Lola Jacquemont, Magnus Hansson, Nassim Kamar, Edmund J. Lamb, Christophe Legendre, Karin Littmann, Christophe Mariat, Toralf Melsom, Lionel Rostaing, Andrew D. Rule, Elke Schaeffner, Per-Ola Sundin, Stephen Turner, Arend Bökenkamp, Ulla Berg, Kajsa Åsling-Monemi, Luciano Selistre, Anna Åkesson, Anders Larsson, Ulf Nyman, Pierre Delanaye
Journal: Annals of Internal Medicine (2020)

The Chronic Kidney Disease in Children Study (CKiD) equation for children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults are recommended serum creatinine (SCr)-based calculations for estimating glomerular filtration rate (GFR). However, these equations, as well as their combination, have limitations, notably the problem of implausible changes in GFR during the transition from adolescence to adulthood and overestimation of GFR in young adults. The full age spectrum (FAS) equation addresses these issues but overestimates GFR when SCr levels are low.To develop and validate a modified FAS SCr-based equation combining design features of the FAS and CKD-EPI equations.Cross-sectional analysis with separate pooled data sets for development and validation.Research and clinical studies (n = 13) with measured GFR available.11 251 participants in 7 studies (development and internal validation data sets) and 8378 participants in 6 studies (external validation data set).Clearance of an exogenous marker (reference method), SCr level, age, sex, and height were used to develop a new equation to estimate GFR.The new European Kidney Function Consortium (EKFC) equation is a FAS equation with low bias (-1.2 mL/min/1.73 m2 [95% CI, -2.7 to 0.0 mL/min/1.73 m2] in children and -0.9 mL/min/1.73 m2 [CI, -1.2 to -0.5 mL/min/1.73 m2] in adults) across the FAS (2 to 90 years) and SCr range (40 to 490 µmol/L [0.45 to 5.54 mg/dL]) and with fewer estimation errors exceeding 30% (6.5% [CI, 3.8% to 9.1%] in children and 3.1% [CI, 2.5% to 3.6%] in adults) compared with the CKiD and CKD-EPI equations.No Black patients were included.The new EKFC equation shows improved accuracy and precision compared with commonly used equations for estimating GFR from SCr levels.Swedish Research Council (Vetenskapsrådet).
Comparative Assessment of the Performance of Pharmacokinetic Tools for Prophylactic Dosing of Antihemophilic Factor Recombinant Plasma/Albumin-Free Method (rAHF-PFM) Concentrate in Patients with Hemophilia A
Authors: Phillip Staibano, Alanna McEneny-King, Massimo Morfini, Gary Foster, Nicholas Hobson, Tamara Navarro-Ruan, Andrea N Edginton, Alfonso Iorio
Journal: Blood (2017)
Glucocorticoids: surprising new findings on their mechanisms of actions
Authors: Frank Buttgereit
Journal: Annals of the Rheumatic Diseases (2020)

Glucocorticoids are highly effective drugs that are used very widely to inhibit inflammation and to modulate the immune system.1–3 Their great importance in the treatment of various rheumatic diseases is undisputed.4–7 However, although their introduction into clinical medicine was more than 70 years ago, we have understood only a fraction of their mechanisms of action. This is mainly due to their highly pleiotropic effects.8 9 A therapeutically used monoclonal antibody against tumour necrosis factor alpha (TNFalpha) neutralises this molecule, and that is it. In contrast, glucocorticoids as hormones regulate an estimated 20% of the entire genome.10 11 The synthesis of cytokines, chemokines, adhesion molecules, receptors and many enzymes, mediators and other proteins is either upregulated or downregulated. In addition, various mechanisms of their action exist whereby we distinguish between genomic and non-genomic effects. These underlying mechanisms of action are known in principle and discussed in detail elsewhere,3 12–14 so the current knowledge is only summarised here in the form of table 1. However, our understanding of glucocorticoid-mediated immunoregulation still has substantial gaps, not only but especially regarding effects of glucocorticoids in specific cell types and their key cellular targets in particular disease states, and the actions these hormones broadly induce in cells and tissues versus those that are unique to the immune system.9 15 

View this table:

Table 1 
Molecular mechanisms of GC actions3 12–14 



Given this background, research in the field of glucocorticoids—sometimes justifiably referred to as ‘old friends’1—continues to be very active. If one enters the search term “glucocorticoids” in PubMed, …
Abstract 16782: A Nationwide Look at Hospitalized Patients With COVID-19 - Clinical Features and Key Events
Authors: Monica R Shah, Tanya F Partridge, Xiaoqiang Xue
Journal: Circulation (2020)

Introduction: While there have been single-center and regional reports describing patients with the coronavirus disease 2019 (COVID-19), to date there has not been a national characterization of hospitalized COVID-19 patients (pts) in the US. Hypothesis: To examine baseline features and key clinical events in US hospitalized COVID-19 pts. Methods: We interrogated a verified US medical claims database from Jan to May 2020 (110 million pts; 76% private insurance claims, 21% Medicare claims, 4% Medicaid claims). Using the COVID-19 ICD-10 code (U07.1), we assessed baseline characteristics, medications, and key event rates in hospitalized COVID-19 pts. Results: From Jan to May 2020, we identified 368,365 pts with a diagnosis of COVID-19. Demographics were: age 60 (IQR 46-72); female sex 198,917 (54%). Key comorbidities were: hypertension 111,940 (30%), coronary artery disease 79,398 (22%), diabetes 70,337 (19%), obesity 33,208 (9%), and heart failure 29,556 (8%). Key medications after admission were: hydroxychloroquine 7,656 (2%), azithromycin 15,361 (4%), methylprednisolone 416 (0.1%), dexamethasone 1,873 (0.5%), and ACE inhibitors/angiotensin receptor blockers/sacubitril-valsartan 18,534 (5%). Among COVID-19 pts, 52,443 (14%) were diagnosed with pneumonia. Key clinical events (ICU admission, intubation, ARDS, and the composite) were significantly higher in COVID-19 pts with pneumonia compared to those without pneumonia (Figure). Conclusions: To the best of our knowledge, this is the first national description of hospitalized COVID-19 pts. We observed an equitable distribution by sex, and high rates of cardiometabolic disease. The rates of key clinical events were significantly higher in COVID-19 pts with pneumonia compared to those without pneumonia. This information can be used in a variety of ways - from refining prognosis, resource planning in hospitals, and estimating event rates for COVID-19 clinical trials.
Abstract 315: Time Adaptive Model for Real-time Cardiopulmonary Resuscitation Outcome Prediction: A Nationwide Out-of-hospital Cardiac Arrest Study
Authors: Ji Woong Kim, Juhyung Ha, Sung Yeon Hwang, Taerim Kim, Wonchul Cha
Journal: Circulation (2020)

Background: OHCA patients use lots of hospital resources, and predicting prognosis is important in decision making for patient treatment. However, no algorithm can predict survival to hospital discharge rates in real-time. Aim: This study aimed to develop and validate the time adaptive model for real-time outcome prediction of OHCA patients. Methods: We performed a retrospective observational study using data from the Korea OHCA Registry in South Korea. In this study, we exclude patients with trauma, experienced ROSC before arriving in the ED, and patient who did not execute CPR in ED to select patients who executed CPR in ED. To develop the time adaptive prediction model, we organize training dataset as ongoing CPR patients by the minute. We used XGBoost as a machine-learning method and find the area under the receiver operating characteristic curve (AUROC) and predict the probability of the time adaptive prediction model. Results: The entire study population is 67270 and the majority were male patients (64%) with a median age of 70 years (IQR 23 years); 2632 (4.0%) had a shockable first documented rhythm at the ED. The subject was split into derivation and validation datasets at a ratio of 8 to 2. The AUROC of the model is 0.72 when the CPR starts, 0.68 after 30 minutes, and 0.62 after 60 minutes. Prediction probability of the time adaptive prediction model is shown in Fig. 1. Conclusions: We developed and validated the time adaptive prediction model by training ongoing CPR patients by minute to predict the CPR outcome of OHCA patients in real-time. This study showed the potential of a machine-learning-based algorithm model for decision making of patients about the termination of resuscitation.
Management of patients after failed peroral endoscopic myotomy: a multicenter study
Authors: Yervant Ichkhanian, Daniella Assis, Pietro Familiari, Michael Ujiki, Baily Su, Sarah R. Khan, Mathieu Pioche, Peter V. Draganov, Joo young Cho, Nikolas Eleftheriadis, Maximilien Barret, Amyn Haji, Vic Velanovich, Marcel Tantau, Jeffrey M. Marks, Amol Bapaye, Alireza Sedarat, Eduardo Albeniz, Robert Bechara, Nikhil A. Kumta, Guido Costamagna, Yaseen B. Perbtani, Mehul Patel, Megan Sippey, Sravan K. Korrapati, Rishabh Jain, Fermín Estremera, Mohamad H. El Zein, Olaya I. Brewer Gutierrez, Mouen A. Khashab
Journal: Endoscopy (2020)

Although peroral endoscopic myotomy (POEM) is highly effective for the management of achalasia, clinical failures may occur. The optimal management of patients who fail POEM is not well known. This study aimed to compare the outcomes of different management strategies in patients who had failed POEM.This was an international multicenter retrospective study at 16 tertiary centers between January 2012 and November 2019. All patients who underwent POEM and experienced persistent or recurrent symptoms (Eckardt score > 3) were included. The primary outcome was to compare the rates of clinical success (Eckardt score ≤ 3) between different management strategies. RESULTS : 99 patients (50 men [50.5 %]; mean age 51.4 [standard deviation (SD) 16.2]) experienced clinical failure during the study period, with a mean (SD) Eckardt score of 5.4 (0.3). A total of 29 patients (32.2 %) were managed conservatively and 70 (71 %) underwent retreatment (repeat POEM 33 [33 %], pneumatic dilation 30 [30 %], and laparoscopic Heller myotomy (LHM) 7 [7.1 %]). During a median follow-up of 10 (interquartile range 3 - 20) months, clinical success was highest in patients who underwent repeat POEM (25 /33 [76 %]; mean [SD] Eckardt score 2.1 [2.1]), followed by pneumatic dilation (18/30 [60 %]; Eckardt score 2.8 [2.3]), and LHM (2/7 [29 %]; Eckardt score 4 [1.8]; P = 0.12). A total of 11 patients in the conservative group (37.9 %; mean Eckardt score 4 [1.8]) achieved clinical success. CONCLUSION : This study comprehensively assessed an international cohort of patients who underwent management of failed POEM. Repeat POEM and pneumatic dilation achieved acceptable clinical success, with excellent safety profiles.
Treatment of Alzheimer's Disease
Authors: R Mayeux, M Sano
Journal: New England Journal of Medicine (1999)

Alzheimer's disease, which is characterized by progressive loss of memory and cognitive function, affects 15 million people worldwide. The incidence increases steadily from 0.5 percent per year at the age of 65 years to nearly 8 percent per year after the age of 85 years.1 Because survival for a decade is common, the prevalence increases from 3 percent at the age of 65 years to 47 percent after the age of 85 years.2 Mutations in the gene for the amyloid precursor protein and the genes for presenilin 1 and 2 cause rare, dominantly inherited forms of the disease occurring before . . .
Placental inflammasome signaling: Protection for mother and baby
Authors: Sabrina Sofia Burgener, Kate Schroder
Journal: The Journal of Experimental Medicine (2020)

The second trimester of pregnancy is traditionally viewed as an immunosuppressive state. Megli et al. (https://doi.org/10.1084/jem.20200649) change this paradigm, showing that midgestation induces inflammasome signaling in placental trophoblasts to promote fetal and maternal antimicrobial defense. The placenta is thus a dynamic immunological organ.
Abstract 13466: Gender and Racial Disparities in Clinical Outcomes Among Patients With Preserved Ejection Fraction Heart Failure
Authors: Chiamaka S Diala, Vivian Chukwuma, Abdulkareem Lukan, Habeeb Sanni, Keziah Aibangbee, Oluwafisayo Fasanmi, Oseiwe Eromosele, Adedotun A Ogunsua, Olakanmi Olagoke, Hawa O Abu, Efehi Igbinomwanhia
Journal: Circulation (2020)

Background: Heart failure is a chronic cardiovascular condition with associated high morbidity, mortality and health-related costs. The disparities of varying sociodemographic factors associated with clinical outcomes in patients with preserved ejection fraction heart failure (HFpEF) is yet to be extensively studied. Aim: To evaluate gender and racial disparities in length of hospital stay (LOS), cost of hospitalization, and in-hospital (IH) mortality in patients with HFpEF. Method: Adults (&gt;18 years) with a primary diagnosis of Acute on Chronic Diastolic dysfunction were identified from the 2016 and 2017 National Inpatient Sample using ICD 10 codes. The relationship between gender or racial groups (Non-Hispanic Whites (NHW)-Ref, Non-Hispanic Blacks (NHB), Hispanics, Asian/Pacific Islanders and Native Americans and study clinical outcomes were assessed using weighted multivariable logistic and linear regression models as appropriate. Results: Among patients with HFpEF (n=595,936), 59.8% were females; 73.4%, 15.6%, 6.6%, 1.9%, and 2.5% were NHW, NHB, Hispanics, Native Americans, and Asians/Pacific Islanders respectively. Females had lower IH mortality [adjusted OR (aOR) 0.9; 95% CI: 0.87 - 0.92) compared to males. Compared to NHW, NHB (aOR 0.81; 95%CI: 0.77 - 0.84) and Hispanics (aOR 0.91; 95%CI: 0.86 - 0.96) had lower odds of IH mortality, while IH mortality in Asian/Pacific Islander and Native American was not significantly different from NHW. Females had lower LOS (mean difference(mD) -0.34 days; 95%CI -0.38 to -0.30) and lower hospital cost (mD -$1967; 95%CI: -2097 to -1838) than males. NHB had similar rates of LOS (mD 0.04days; 95%CI: -0.02 - 0.11) and hospital cost (mD -$176; 95%CI: -412 - 60) compared to NHW. Hispanics had similar rates of LOS but higher hospital cost (mD 0.07 days; 95%CI -0.04 - 0.18; mD $1182; 95%CI: 754 - 1609), Asians/Pacific Islander (mD 0.32 days; 95%CI: 0.14 - 0.49, mD $2846; 95%CI 2173 - 3519) and Native American had a higher LOS and hospital cost compared to NHW (mD 0.49 days; 95%CI: 0.33 - 0.64, mD $2793; 95%CI: 2048 - 3539). Conclusion: Our study highlights racial and gender disparities in important clinical outcomes among patients with HFpEF, buttressing the need to tailor intervention to higher risk groups.
Abstract 10789: TRACP5b is Associated With High Mortality in Hospitalized Patients With Heart Failure
Authors: Satoshi Abe, Akiomi Yoshihisa, Yusuke Kimishima, Yu Sato, Yuki Kanno, Tetsuro Yokokawa, Tomofumi Misaka, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2019)

Introduction: Tarterate-resistant acid phosphatase Type 5b (TRACP5b) is derived from osteoclast, and elevated in patients with osteoporosis. Heart failure (HF) is associated with catabolic bone rem...
Abstract 17177: Furosemide Promotes Myocardial Fibrosis in Swine Heart Failure
Authors: Nisha Plavelil, Mark C Haigney, Robert E Goldstein, Michael Klein, Matie Shou, Luke Michaelson, Vincent B Ho, Maureen N Hood
Journal: Circulation (2020)

Introduction: Although frequently used in heart failure (HF), long-term furosemide exacerbates HF in a swine model. This paradoxical phenomenon may reflect furosemide-induced alterations in signaling proteins of the extracellular matrix (ECM) to increase fibrosis. Examination of the ECM may clarify how treatments like furosemide enhance the progression of HF. Hypothesis: The administration of furosemide increased inflammation and fibrosis of the heart, leading to accelerated HF deterioration in a swine model. Methods: After Institutional Animal Care and Use Committee (IACUC) approval, Yorkshire swine (N=10, 5 = furosemide, 5 = saline) were paced 3 to 5 weeks at 200 beats per minute to induce HF (left ventricular fractional shortening &lt;16% on echocardiogram). Animals were treated with furosemide (1 mg/kg intramuscularly) or saline. Western Blot and histology with Masson’s trichrome stain were performed on transmural LV myocardium to quantify critical determinants of fibrosis. ANOVA with Tukey HSD correction and descriptive statistics were performed using SPSS with significance by α of 0.05; mean ± SEM. Results: The overall increase in ECM fibrosis in HF was clearly demonstrated on Masson’s trichrome histology associated with significant, uniform increase in signaling pathways leading to fibrosis associated with furosemide use. SMAD 2-HF Furosemide to Control (p&lt;.05): HF Furosemide 0.266 ±.05, HF Saline 0.183±.02, Control 0.163±.01 ERK-all (p&lt;.05): HF Furosemide 0.312±.02, HF Saline 0.209±.01,Control 0.149±.01 GDF-15-HF Furosemide to Control (p&lt;.05): HF Furosemide 0.095 ±.00, HF Saline 0.073±.01, Control 0.062±.01 MMP-14-all (p&lt;.05): HF Furosemide 0.451±.02, HF Saline 0.374±.03,Control 0.231±.02 TIMP-1-all (p&lt;.05): HF Furosemide 0.184±.01, HF Saline 0.0135±.03,Control 0.033±.01 PAI-1-all (p&lt;.05): HF Furosemide 0.105±.01, HF Saline 0.046±.01,Control 0.043±.00 Conclusions: Histologic and biochemical analysis showed worsening HF in furosemide-treated paced swine was associated with consistent increases in fibrosis and indices of adverse ECM remodeling. The diuretic intended to reduce water retention during HF appeared to enhance myocardial fibrosis, paradoxically accelerating pathological processes responsible for HF.