tbuckley/cabot-search huggingface dataset:
Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19
Authors: Eric J. Lenze, Caline Mattar, Charles F. Zorumski, Angela Stevens, Julie Schweiger, Ginger E. Nicol, J. Philip Miller, Lei Yang, Michael Yingling, Michael S. Avidan, Angela M. Reiersen
Journal: JAMA (2020)

Coronavirus disease 2019 (COVID-19) may lead to serious illness as a result of an excessive immune response. Fluvoxamine may prevent clinical deterioration by stimulating the σ-1 receptor, which regulates cytokine production.To determine whether fluvoxamine, given during mild COVID-19 illness, prevents clinical deterioration and decreases the severity of disease.Double-blind, randomized, fully remote (contactless) clinical trial of fluvoxamine vs placebo. Participants were community-living, nonhospitalized adults with confirmed severe acute respiratory syndrome coronavirus 2 infection, with COVID-19 symptom onset within 7 days and oxygen saturation of 92% or greater. One hundred fifty-two participants were enrolled from the St Louis metropolitan area (Missouri and Illinois) from April 10, 2020, to August 5, 2020. The final date of follow-up was September 19, 2020.Participants were randomly assigned to receive 100 mg of fluvoxamine (n = 80) or placebo (n = 72) 3 times daily for 15 days.The primary outcome was clinical deterioration within 15 days of randomization defined by meeting both criteria of (1) shortness of breath or hospitalization for shortness of breath or pneumonia and (2) oxygen saturation less than 92% on room air or need for supplemental oxygen to achieve oxygen saturation of 92% or greater.Of 152 patients who were randomized (mean [SD] age, 46 [13] years; 109 [72%] women), 115 (76%) completed the trial. Clinical deterioration occurred in 0 of 80 patients in the fluvoxamine group and in 6 of 72 patients in the placebo group (absolute difference, 8.7% [95% CI, 1.8%-16.4%] from survival analysis; log-rank P = .009). The fluvoxamine group had 1 serious adverse event and 11 other adverse events, whereas the placebo group had 6 serious adverse events and 12 other adverse events.In this preliminary study of adult outpatients with symptomatic COVID-19, patients treated with fluvoxamine, compared with placebo, had a lower likelihood of clinical deterioration over 15 days. However, the study is limited by a small sample size and short follow-up duration, and determination of clinical efficacy would require larger randomized trials with more definitive outcome measures.ClinicalTrials.gov Identifier: NCT04342663.
Abstract 12889: Clathrin-mediated Endocytosis Plays a Key Role in Stem Cell Therapy for Ischemic Heart Disease
Authors: Shunsuke Eguchi, Mikito Takefuji, Toyoaki Murohara
Journal: Circulation (2020)

Background and Aim: Cell therapy represents a potential frontier to transform the treatment and prognosis of heart failure and acute myocardial infarction (AMI). Extracellular vesicles (EVs) have come out as key mediators of intercellular communication to improve cardiac function in cell therapy. However, the mechanisms by which cardiomyocytes respond to EVs remain unclear. Here, we sought to clarify the effect of cardiomyocyte endocytosis on AMI. Methods and Results: Treatment with the culture supernatant of adipose-derived regenerative cells (ADRCs) prevented cardiomyocyte cell damage under conditions of hypoxia in vitro. In vivo, the injection of ADRCs in the heart simultaneous with coronary artery ligation decreased infarct area in the heart in a dose-dependent manner. In addition, the injection of ADRCs prevented cardiac rupture after AMI and significantly reduced apoptosis in cardiomyocytes at 1 and 2 days. To examine the efficacy of cardiomyocyte endocytosis, cardiomyocytes were cultured with EVs previously isolated from ADRC culture supernatant and labeled with the fluorescent dye, PKH67. Notably, hypoxic culture conditions increased the intensity of the labeled EVs in cardiomyocytes. An inhibitor of clathrin-mediated endocytosis (chlorpromazine), but not inhibitors of caveolae-mediated endocytosis, micropinocytosis, and phagocytosis (genistein, cytochalasin D, or amiloride), significantly suppressed the ADRC culture supernatant-induced decreases of hypoxia-damaged cardiomyocytes. Chlorpromazine treatment also decreased hypoxia-induced cardiomyocyte capture of labeled EVs secreted from ADRCs. To investigate whether communication between cardiomyocytes and ADRCs affords cardiac protection through clathrin-mediated endocytosis in vivo, mice were treated with ADRCs alone or in combination with chlorpromazine following coronary artery ligation. Chlorpromazine treatment failed to show ADRC-induced cardiac protection such as prevention of cardiac rupture and anti-apoptotic effect. Conclusions: Our results indicate that EVs secreted from ADRCs prevent cardiac rupture after AMI and that clathrin-mediated endocytosis plays a critical role in transporting the EVs into cardiomyocytes.
PREDICTORS OF OUTCOMES OF COVID-19 IN PATIENTS WITH CHRONIC LIVER DISEASE: US MULTI-CENTER STUDY
Authors: Adeniji, Nia, Kim, Donghee, Latt, Nyan L., Kumar, Sonal, Bloom, Patricia P., Elizabeth S. Aby, Ponni V. Perumalswami, Roytman, Marina, Li, Michael, Vogel, Alexander S., Andreea M. Catana, Wegermann, Kara, Carr, Rotonya M., Zhou, Kali, Lizaola-Mayo, Blanca, Debes, Jose D., Lee, Tzu-Hao, Branch, Andrea D., Viveiros, Kathleen, Chan, Walter W., David M. Chascsa, Paul Y. Kwo, Renumathy Dhanasekaran
Journal: Hepatology (2020)
Abstract 15076: County-level Subgroups With Unique Cardiovascular Outcomes: An Unsupervised Clustering Analysis
Authors: Matthew W Segar, Shreya Rao, Amy E Hughes, Ambarish Pandey
Journal: Circulation (2020)

Introduction: Regional heterogeneity in cardiovascular disease (CVD) risk has been demonstrated in the United States (US), however associations between county-level social and demographic risk factors and CVD mortality have not previously been described. To address this, we evaluated whether unsupervised machine learning-based clustering could identify distinct US county subgroups with unique CVD outcomes. Methods: The study included 2,676 counties from the 2020 County Health Rankings program. Unsupervised hierarchical clustering of 46 candidate variables encompassing demographic, health behaviors, socioeconomic factors, and healthcare access domains was used to derive phenogroups. The association of phenogroups and age-adjusted CVD mortality was assessed by linear regression. Results: Clustering identified 4 phenogroups based on within-cluster inertia. Cluster 1 (N=924; 24.5%) counties were largely white, suburban households with high income and access to healthcare. Cluster 2 counties (N=451; 16.9%) were large with predominantly Hispanic residents and below average prevalence of CVD risk factors. Cluster 3 (N=951; 35.5%) counties included rural, white residents with the lowest levels of healthcare access. Cluster 4 (350; 13.1%) counties were comprised of predominantly black residents with substantial cardiovascular comorbidities and physical and socioeconomic burdens. Age-adjusted cardiovascular mortality increased in a stepwise fashion from 247 in cluster 1 to 349 per 100,000 residents in cluster 4 (FigA) with the phenogroups demonstrating regionality across the US (FigB). Addition of phenogroup in linear regression improved model performance with a R 2 of 0.70. Conclusions: Unsupervised machine learning clustering based on demographic and behavior data can identify unique county phenogroups with differential risk of CVD mortality and may aid in identifying communities at highest risk for CVD-related adverse events.
Abstract 17133: The Use of Novel Hematological Markers in Predicting Stroke After TAVR Using a Machine Learning Algorithm
Authors: Aliaskar Z Hasani, Kusha Rahgozar, Aaron Wengrofsky, Narasimha Kuchimanchi, Mohammad Hashim Mustehsan, Azeem Latib, Ythan Goldberg
Journal: Circulation (2020)

Introduction: Aortic Stenosis is the most common valvular disorder with a predominance in the elderly. Trans-Aortic Valve Replacement (TAVR) has been an effective procedure with marked improvement in quality of life for patients. The procedure carries a small, yet clinically significant risk of stroke. The use of Neutrophil-Lymphocyte Ratios (NLR) and Platelet-Lymphocyte Ratios (PLR) have been growing as novel markers of systemic inflammation. We investigated the ability of a machine learning algorithm (Light GBM) to predict and weigh these ratios along with other clinical parameters for prediction of stroke after TAVR. Objective: To demonstrate the efficacy of the Supervised Machine Learning algorithm, Light GBM, in identifying important variables to predict stroke after TAVR. Methods: We performed a retrospective analysis of 291 patients who underwent TAVR from 2015-2019 at Montefiore Medical Center. Age (80±8), 50.2% Female, BMI (28.7 ±6.3). Clinical data was collected through our Hospital EMR. NLR and PLR averages were obtained using the mean of baseline (prior to surgery), Immediate Post-operative, and Post-operative Day 1 values. A supervised machine learning algorithm, Light GBM, used decision tree algorithms with both level-wise growth and leaf-wise growth. The algorithm was trained on 80% of the data and internally validated on the other 20%. Results: We identified NLR and PLR as the second and third most important feature of importance (Table 1) Clinical and demographic features of importance included BMI, Age, and Sex. Our model when internally validated yield a Sensitivity of 75.0%, Specificity of 91.5%, Accuracy of 91.5%, and F1 of 0.75. The AUC for the model was 0.84. Conclusions: Using Novel hematological parameters in conjunction with machine learning algorithms have highlighted important variables in predicting stroke after TAVR. Extrapolated, average NLR and PLR can be an inexpensive tool in stratifying patients those patients most at risk.
Abstract 14672: Differential Risk Factor Profiles and Management of Acute Coronary Syndrome in Us Women With or Without Active Breast Cancer
Authors: Robert Weidling, Prakash Acharya, Zubair Shah, Charles Porter
Journal: Circulation (2020)

Introduction: Acute Coronary Syndrome (ACS) and breast cancer are major contributors to United States mortality. Breast cancer is a known risk factor for coronary artery disease, yet questions remain regarding the clinical impact of the intersection of these two diseases. We evaluated the patient characteristics, interventions and outcomes during ACS hospitalizations of US women with active breast cancer. Methods: We retrospectively analyzed the US National Readmissions Database years 2016-2017 to identify adult women with or without active breast cancer admitted with ACS defined asUA, NSTEMI or STEMI. Differences in baseline characteristics, interventions, and in-hospital mortality of these two groups were determined and analyzed. Results: Among 544,698 ACS cases in adult women identified, 2,782 (0.52%) had active breast cancer. Those with breast cancer were 3 years younger (mean age 69 vs 72 years, p &lt; .001), and had significantly lower prevalences of dyslipidemia, hypertension, obesity and tobacco use. Although incidence of STEMIs were equivalent in both groups, those with breast cancer were less likely to undergo PCI (28.8% vs 34.36%, P&lt;0.001) or CABG (5.67% vs 8.89%, p&lt;0.001). Complication rates were not significantly different between groups, but those with breast cancer were less likely to undergo CPR in case of cardiac arrest (0.96% vs 1.47%, p =0.027). No significant difference was found between inpatient mortality rates or readmission rates. Conclusions: Women admitted for ACS with active breast cancer were younger and had more favorable CV risk profiles compared to those without breast cancer. These findings suggest that the presence of breast cancer is associated with a risk of ACS that is inadequately recognized by conventional CV risk assessment tools. Despite the more favorable CV risk profiles, STEMI rates were equivalent between groups, but revascularization was less common in those with breast cancer. Comparable outcomes with less invasive therapies suggest a difference in ACS pathophysiology. More specific predictive tools for ACS in the breast cancer population may be needed especially in light of contemporary era hormonal and targeted therapies which are increasing the rate of survivorship.
Abstract 13445: Patterns and Outcomes of Thoracic Organ Transplantation Across Citizenship Status in the United Status
Authors: Lauren Sinnenberg, Sara R Machado, John Ostrominski, Josef Stehlik, Mandeep R Mehra, Muthiah Vaduganathan
Journal: Circulation (2020)

Introduction: The volume of solid organ transplantation in the US has increased in recent years. Few data are available characterizing thoracic transplantation patterns and outcomes by citizenship status. Methods: Citizenship at the time of transplantation was characterized among thoracic organ transplantation recipients in the US between 2013 and 2018 using United Network for Organ Sharing data. The non-US citizen group included non-US citizen/US residents, non-US citizen/non-US residents who travelled to the US for transplantation, and non-US citizen/non-US residents who travelled to the US for reasons other than transplantation. Cox regression models were constructed to examine the association between citizenship status and death or graft failure, accounting for age, sex, race, and payment method. Results: Among 31,174 thoracic organ transplantations, number of non-US citizen thoracic organ recipients increased from 90 in 2013 to 221 in 2018 (a 146% increase). Proportion of non-US citizen recipients (of all recipients) similarly increased from 2.0% in 2013 to 3.7% in 2018 (Figure 1a). Non-US citizens were, on average, younger than US citizens (46±19 vs 51±19 years, p&lt;0.001) and were less likely to be supported by Medicaid (13% vs. 22%, p&lt;0.001). By 6 months, there were 2,228 deaths or graft failures, which similarly occurred among non-US citizens and US-citizens (6.1% vs 6.8%, P=0.38) (Figure 1b). Non-US citizens did not experience higher covariate-adjusted risk of post-transplant death or graft failure compared with US citizens (adj. HR 0.93; 95% CI 0.70-1.25; P=0.64). Conclusions: Between 2013 and 2018, there was a modest increase in non-US citizen recipients of thoracic organ transplantation. Non-US citizens have similar risk-adjusted patient and graft survival when undergoing thoracic organ transplantation compared with US citizens.
Abstract 119: Association of Acute Exposure to Ambient Air Particulate Matter and Ozone with Risk of Out-of-hospital Cardiac Arrest
Authors: Ali Malik, Philip Jones, Robert Brook, Andy T Tran, Paul S Chan
Journal: Circulation (2020)

Introduction: Acute exposure to particulate matter &lt; 2.5 μm in diameter (PM 2.5 ) and ozone have been associated with increased all-cause mortality in the U.S. Whether these ambient air pollutants are specifically associated with a higher risk of out-of-hospital cardiac arrest (OHCA) is unknown. Methods: Within the Cardiac Arrest Registry to Enhance Survival, we identified 187,047 individuals with non-traumatic OHCA during 2013-2016 that could be linked to EPA data. We estimated an individual’s exposure to PM 2.5 and ozone using data from the EPA’s Fused Air Quality Surface using a Downscaling tool, which integrates monitoring station data with atmospheric models to predict daily levels by census tract. The associations of acute exposure to PM 2.5 and ozone with OHCA were examined using a time-stratified case-crossover design. Case day was defined as the day of the OHCA. Associations were also assessed for moving average across days 0-1 (lag 1) and days 0-2 (lag 2). Control days were defined as the same weekday from the preceding 2 weeks. Associations were estimated using conditional logistic regression on PM 2.5 and ozone, stratified by patient. We also explored if associations varied by age, sex, race and OHCA rhythm. Results: Mean age was 62.6 ± 19.4 years, 61.1% were male, and 52.6% non-White. Mean pollutant concentrations on case day were 9.2 ± 4.9 μg/m 3 PM 2.5 and 36.9 ± 12.1 parts per billion (ppb) ozone. We found a significant effect of ozone on the case day with a 1.1% increase in odds of OHCA per +12 ppb greater ozone level. There was no association with PM 2.5 on either case or lag days, and no association with ozone on lag days (Table). There was no interaction of age, sex, race and OHCA rhythm with PM 2.5 or ozone with risk of OHCA on either case or any lag days (p &gt;0.2 for all). Conclusion: In the U.S. exposure to higher ozone levels, but not PM 2.5 , was associated with a higher risk of OHCA. Mechanisms by which acute ozone exposure increases risk need to be better defined.
Functionally informed fine-mapping and polygenic localization of complex trait heritability
Authors: Omer Weissbrod, Farhad Hormozdiari, Christian Benner, Ran Cui, Jacob Ulirsch, Steven Gazal, Armin P. Schoech, Bryce van de Geijn, Yakir Reshef, Carla Márquez-Luna, Luke O’Connor, Matti Pirinen, Hilary K. Finucane, Alkes L. Price
Journal: Nature Genetics (2020)
Southeast Asian health system challenges and responses to the ‘Andaman Sea refugee crisis’: A qualitative study of health-sector perspectives from Indonesia, Malaysia, Myanmar, and Thailand
Authors: Helena Legido-Quigley, Fiona Leh Hoon Chuah, Natasha Howard
Journal: PLoS Medicine (2020)

Background Southeast Asian countries host signficant numbers of forcibly displaced people. This study was conducted to examine how health systems in Southeast Asia have responded to the health system challenges of forced migration and refugee-related health including the health needs of populations affected by forced displacement; the health systems–level barriers and facilitators in addressing these needs; and the implications of existing health policies relating to forcibly displaced and refugee populations. This study aims to fill in the gap in knowledge by analysing how health systems are organised in Southeast Asia to address the health needs of forcibly displaced people. Methods and findings We conducted 30 semistructured interviews with health policy-makers, health service providers, and other experts working in the United Nations ( n = 6), ministries and public health ( n = 5), international ( n = 9) and national civil society ( n = 7), and academia ( n = 3) based in Indonesia ( n = 6), Malaysia ( n = 10), Myanmar ( n = 6), and Thailand ( n = 8). Data were analysed thematically using deductive and inductive coding. Interviewees described the cumulative nature of health risks at each migratory phase. Perceived barriers to addressing migrants’ cumulative health needs were primarily financial, juridico-political, and sociocultural, whereas key facilitators were many health workers’ humanitarian stance and positive national commitment to pursuing universal health coverage (UHC). Across all countries, financial constraints were identified as the main challenges in addressing the comprehensive health needs of refugees and asylum seekers. Participants recommended regional and multisectoral approaches led by national governments, recognising refugee and asylum-seeker contributions, and promoting inclusion and livelihoods. Main study limitations included that we were not able to include migrant voices or those professionals not already interested in migrants. Conclusions To our knowledge, this is one of the first qualitative studies to investigate the health concerns and barriers to access among migrants experiencing forced displacement, particularly refugees and asylum seekers, in Southeast Asia. Findings provide practical new insights with implications for informing policy and practice. Overall, sociopolitical inclusion of forcibly displaced populations remains difficult in these four countries despite their significant contributions to host-country economies.
Abstract 218: Novel Blood Biomarker Taurine and Glutamate for Early Predicting Outcomes After Out-of-hospital Cardiac Arrest
Authors: Jing Li, Kevin Qin, Pratik B Doshi, Xiangdong Zhu, Pavitra Kotini-Shah, Misha Granado, Hajwa Kim, Pei-Shan Yen, Richard Gordon, Henry E Wang, Terry L Vanden Hoek
Journal: Circulation (2020)

Introduction: Out-of-Hospital cardiac arrest (OHCA) is the leading cause of death with an overall survival rate of less than 10%. Organ failure and metabolic impairment are two critical elements of post-CA syndrome. Taurine and glutamate are amino acids that are expressed primarily in heart and brain. The compensatory release during osmotic stress, as seen in CA, amplifies reperfusion injury, heart stunning and brain edema. Thus, taurine and glutamate concentrations in blood likely reflects the extent of injury in the heart and brain following CA. Hypothesis: Plasma taurine and glutamate concentration correlates with CA outcomes. Methods: Adult OHCA patients (n=37) at an urban academic ED were enrolled from 2018-2019. Among them, 14 were survivors (S) and 23 were nonsurvivors (NS). Blood samples were collected at various time points including the time at hospital arrival, 6, 24, 48, 72 hours after arrival (T0, 6, 24, 48 and 72 h, respectively), and measured. T-test and GEE were used for mean comparison and longitudinal trend analysis, respectively. p &lt; 0.05 was considered as statistically significant. Results: Plasma taurine and glutamate concentrations were compared between S and NS at T0 and across all time points. Both concentrations were significantly higher in NS vs S group at T0 (for taurine: 77.7 ± 40.0 in NS vs. 60.0 ± 31.9 μM in S, p =0.014; for glutamate: 176.4 ± 98.7 in NS vs. 162.8 ± 111.1 μM in S, p =0.0496), and showed a decreasing trend over time. In the first 6 h, taurine and glutamate level decreased more in S group than NS group (over 30% drop in S compared to &lt;15% drop in NS). In addition, a positive correlation of cerebral performance category was seen at T6 with taurine (p=0.0354), but not with glutamate. Conclusions: Blood taurine and glutamate may serve as early biomarkers in predicting OHCA outcomes. Monitoring their change over time can help physicians tailor treatment decisions and patient management.
Abstract 16331: Prevalence and Outcomes of Arrhythmia in Tumor Lysis Syndrome: A National Perspective
Authors: Rupak Desai, Akhil Jain, Sandeep Singh, Mohammed Faisaluddin, Faizan Ahmad Malik, Virmitra Desai, Vraj Shah, falah abu hassan, Zarna Bambhroliya, Rushik Bhuva
Journal: Circulation (2020)

Introduction: Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency. Epidemiology and mortality outcomes of arrhythmia in TLS are scarcely studied in the literature. Methods: We used the National Inpatient Sample (NIS) to study the prevalence and outcome of arrhythmia in patients hospitalized with TLS (ICD-9 code 277.88) from 2009-2014. Multivariable regression was performed to analyze TLS-related mortality. Results: A total of 9034 cases of arrhythmia among 37,861 TLS patients were identified. The trends in the prevalence of arrhythmia were stable with rates ranging from 19.8% to 25.8%, with the highest frequency recorded in 2014 (25.8%) (Fig. 1A). Atrial fibrillation (13.6%) was the most common arrhythmia followed by ventricular tachycardia in 2.6% of the patients (Fig. 1B). Sixty-seven percent of arrhythmias were among white old (&gt;65) males. Arrhythmic cohort showed a higher frequency of comorbidities like fluid-electrolyte disturbances, congestive heart failure, renal failure, pulmonary circulatory disorders, deficiency anemias, etc. The most common malignancies were leukemia and lymphoma. Overall in-hospital mortality (32% vs 21.3%), the median length of stay (11 vs. 9 days) and hospital charges were higher among arrhythmic TLS patients. Conclusions: In this population-based analysis, arrhythmia in TLS was associated with higher odds of mortality and increased resource utilization. Strategies to improve the management of TLS to prevent arrhythmia is of utmost importance.