tbuckley/cabot-search huggingface dataset:
Association of NO<sub>2</sub> and Other Air Pollution Exposures With the Risk of Parkinson Disease
Authors: Sungyang Jo, Ye-Jee Kim, Kye Won Park, Yun Su Hwang, Seung Hyun Lee, Bum Joon Kim, Sun Ju Chung
Journal: JAMA Neurology (2021)

<h3>Importance</h3> The development of Parkinson disease (PD) may be promoted by exposure to air pollution. <h3>Objective</h3> To investigate the potential association between exposure to particulate matters (PM<sub>2.5</sub>and PM<sub>10</sub>), nitrogen dioxide (NO<sub>2</sub>), ozone (O<sub>3</sub>), sulfur dioxide (SO<sub>2</sub>), and carbon monoxide (CO) and the risk of incident PD. <h3>Design, Setting, and Participants</h3> This retrospective cohort study used data from the Korean National Health Insurance Service. Among the 1 021 208 Korean individuals in the database, those who had lived in Seoul from January 2002 to December 2006 (n = 176 875) were screened for eligibility. A total of 78 830 adults older than 40 years without PD and who lived in Seoul between January 2002 and December 2006 were included in this study. Individuals diagnosed with PD before 2006 (n = 159) and individuals 40 years or younger (n = 97 886) were excluded. Each participant was followed up with annually from January 2007 to December 2015, thereby adding up to 757 704 total person-years of follow-up. Data were analyzed from January to September 2020. <h3>Exposures</h3> Individual exposure levels to PM<sub>2.5</sub>, PM<sub>10</sub>, NO<sub>2</sub>, O<sub>3</sub>, SO<sub>2</sub>, and CO were estimated based on the participants’ residential address at the district level. To evaluate long-term exposure to air pollution, time-varying 5-year mean air pollutant exposure was calculated for each participant. <h3>Main Outcomes and Measures</h3> The outcome measure was the association between air pollution and the risk of incident PD measured as hazard ratios after adjusting for demographic factors, socioeconomic factors, and medical comorbidities. <h3>Results</h3> At baseline, the mean (SD) age of the 78 830 participants was 54.4 (10.7) years, and 41 070 (52.1%) were female. A total of 338 individuals with newly diagnosed PD were identified during the study period. Exposure to NO<sub>2</sub>was associated with an increase in risk of PD (hazard ratio for highest vs lowest quartile, 1.41; 95% CI, 1.02-1.95;<i>P</i>for trend = .045). No statistically significant associations between exposure to PM<sub>2.5,</sub>PM<sub>10</sub>, O<sub>3</sub>, SO<sub>2</sub>, or CO and PD incidence were found. <h3>Conclusions and Relevance</h3> In this large cohort study, a statistically significant association between NO<sub>2</sub>exposure and PD risk was identified. This finding suggests the role of air pollutants in PD development, advocating for the need to implement a targeted public health policy.
Abstract 12624: Pathological Analysis Reveals Causes of Poor Patency After Endovascular Therapy for Below-the-knee Lesions
Authors: Katsumi Inoue, Yusuke Tomoi, Yoshimitsu Soga, Kenji Ando, Takeshi Kimura
Journal: Circulation (2020)

Introduction: Endovascular therapy for below-the-knee (BTK) lesions often ends in unsatisfactory outcomes not only by balloon angioplasty (BA) alone but also by adding drug-eluting stent (DES) implantation to BA. We assessed the hypothesis that a histopathological analysis of the amputated tissues would reveal the causes of poor patency after BTK endovascular therapy. Methods: We examined tissue specimens from BTK lesions obtained by surgical resection after BA alone (n = 15) and after BA and DES implantation (n = 9). All of them were 100 mm or more in length and had rapid worsening of distal leg ischemia within three months after successful revascularization. More than 60% of them had chronic total occlusion. DESs for coronary arteries of similar sizes were repurposed and used for BTK arteries (drug type: everolimus; size: 2.5-3.0 mm х 28-38 mm). Results: Histologically, severe atherosclerosis and intimal-medial calcification were observed in all specimens. Many cases treated by BA alone suffered large semilunar dissection caused by guide-wire failure via the true lumen. There were cases where initial luminal expansion was impaired by vessel shrinkage, in which significant intimal-medial disruption, medial dissection, and massive thrombus formation were observed. Also, there were cases where remarkable lumen loss was caused by neointima formation with a considerable amount of smooth muscle cells and proteoglycan. All cases treated by BA and DES implantation suffered total lumen occlusion due to thrombi which were organized by moderate smooth muscle cell proliferation. Their proximal edge segments had moderate to severe intimal hyperplasia caused by balloon dilatation. Three DESs implanted in the middle portion of the BTK lesions were markedly deformed under compression by the surrounding muscles. Conclusions: After BTK endovascular therapy, cases treated by BA alone had poor patency due to insufficient luminal expansion, whereas those treated by BA and DES implantation had organized thrombus formation caused by slow and limited flow inside the DES due to intimal hyperplasia in the proximal segment. Smooth muscle cell proliferation inside the DES may be inhibited by the effect of the drug coated on the DES.
An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility
Authors: Liuyang Wang, Thomas J. Balmat, Alejandro L. Antonia, Florica J. Constantine, Ricardo Henao, Thomas W. Burke, Andy Ingham, Micah T. McClain, Ephraim L. Tsalik, Emily R. Ko, Geoffrey S. Ginsburg, Mark R. DeLong, Xiling Shen, Christopher W. Woods, Elizabeth R. Hauser, Dennis C. Ko
Journal: Genome Medicine (2021)

Abstract Background While genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to pathophysiology remains an important challenge. Methods are needed to systematically bridge this crucial gap to facilitate experimental testing of hypotheses and translation to clinical utility. Results Here, we leveraged cross-phenotype associations to identify traits with shared genetic architecture, using linkage disequilibrium (LD) information to accurately capture shared SNPs by proxy, and calculate significance of enrichment. This shared genetic architecture was examined across differing biological scales through incorporating data from catalogs of clinical, cellular, and molecular GWAS. We have created an interactive web database (interactive Cross-Phenotype Analysis of GWAS database (iCPAGdb)) to facilitate exploration and allow rapid analysis of user-uploaded GWAS summary statistics. This database revealed well-known relationships among phenotypes, as well as the generation of novel hypotheses to explain the pathophysiology of common diseases. Application of iCPAGdb to a recent GWAS of severe COVID-19 demonstrated unexpected overlap of GWAS signals between COVID-19 and human diseases, including with idiopathic pulmonary fibrosis driven by the DPP9 locus. Transcriptomics from peripheral blood of COVID-19 patients demonstrated that DPP9 was induced in SARS-CoV-2 compared to healthy controls or those with bacterial infection. Further investigation of cross-phenotype SNPs associated with both severe COVID-19 and other human traits demonstrated colocalization of the GWAS signal at the ABO locus with plasma protein levels of a reported receptor of SARS-CoV-2, CD209 (DC-SIGN). This finding points to a possible mechanism whereby glycosylation of CD209 by ABO may regulate COVID-19 disease severity. Conclusions Thus, connecting genetically related traits across phenotypic scales links human diseases to molecular and cellular measurements that can reveal mechanisms and lead to novel biomarkers and therapeutic approaches. The iCPAGdb web portal is accessible at http://cpag.oit.duke.edu and the software code at https://github.com/tbalmat/iCPAGdb .
Ongoing and future COVID-19 vaccine clinical trials: challenges and opportunities
Authors: Rafael Dal-Ré, Linda-Gail Bekker, Christian Gluud, Søren Holm, Vivekanand Jha, Gregory A Poland, Frits R Rosendaal, Brigitte Schwarzer-Daum, Esperança Sevene, Halidou Tinto, Teck Chuan Voo, Nadarajah Sreeharan
Journal: The Lancet Infectious Diseases (2021)
Abstract 15673: Racial Disparities in Referral for Pre-operative Cardiovascular Evaluation, Surgical Wait Time, and Weight Loss in Patients Undergoing Bariatric Surgery
Authors: Lauren Tragesser, Kaitlyn Ibrahim, Rohit Soans, Abdullah Haddad, Raj K Dalsania, Vikram Eddy, Liti Zhang, Joseph McComb, Martin G Keane, Isaac Whitman
Journal: Circulation (2020)

Introduction: White patients undergo bariatric surgery more frequently and with fewer complications compared to non-white patients. Yet, racial disparities in referral pattern for preoperative cardiovascular evaluation (CVE) are unexplored. We hypothesized that racial disparities exist in preoperative CVE in white vs. non-white patients undergoing bariatric surgery. Methods: We identified consecutive patients undergoing bariatric surgery at our institution from 2014-2018. The association of white vs. non-white race with referral for CVE, cardiac testing, surgical wait time, and postoperative weight loss was determined in a multivariate model adjusting for baseline demographic comorbidities and income. Additional adjustment for insurance provider was made for surgical wait time. Results: Of the 797 patients undergoing bariatric surgery during the study period, 86% (n=682) were non-white. White vs. non-white patients had similar age, gender distribution, and prevalence of hypertension, hyperlipidemia, Type 2 diabetes, and heart failure. A similar proportion of whites vs. non-whites were referred to cardiology for pre-operative evaluation (65% vs. 68%, p=0.52), while whites were more likely to undergo further preoperative cardiac testing after adjustment (68% vs. 55%, p=0.04; adjusted, OR 0.6, 95%CI 0.35-1.0, p=0.05). Despite less cardiac testing, non-white patients referred to cardiology waited longer for surgery (9.9 months vs. 12.1 months, p=0.008), including after adjustment (HR 0.7, 95%CI 0.53-0.91, p= 0.008. Weight loss at 6 months was higher in whites (12.9 kg/m 2 vs. 11.95 kg/m 2 , p=0.03), but equivalent at 1 year (whites 14.9 kg/m 2 vs. non-whites 14.3 kg/m 2 , p=0.33). Conclusions: In a bariatric surgery population, white vs. non-white patients were referred for CVE in similar proportion. However, white patients underwent more subsequent cardiac testing pre-operatively when compared to non-whites yet had a shorter wait time for surgery. Early weight loss was greater in whites, but equivalent between groups at 1 year.
Cardiovascular Safety of Hydroxychloroquine in US Veterans With Rheumatoid Arthritis
Authors: Charles Faselis, Qing Zeng‐Treitler, Yan Cheng, Gail S. Kerr, David J. Nashel, Angelike P. Liappis, Amy C. Weintrob, Pamela E. Karasik, Cherinne Arundel, Denise Boehm, Michael S. Heimall, Lawrence B. Connell, Daniel D. Taub, Yijun Shao, Douglas F. Redd, Helen M. Sheriff, Sijian Zhang, Ross D. Fletcher, Gregg C. Fonarow, Hans J. Moore, Ali Ahmed
Journal: Arthritis & Rheumatology (2021)

Hydroxychloroquine (HCQ) may prolong the QT interval, a risk factor for torsade de pointes, a potentially fatal ventricular arrhythmia. This study was undertaken to examine the cardiovascular safety of HCQ in patients with rheumatoid arthritis (RA).We conducted an active comparator safety study of HCQ in a propensity score-matched cohort of 8,852 US veterans newly diagnosed as having RA between October 1, 2001 and December 31, 2017. Patients were started on HCQ (n = 4,426) or another nonbiologic disease-modifying antirheumatic drug (DMARD; n = 4,426) after RA diagnosis, up to December 31, 2018, and followed up for 12 months after therapy initiation, up to December 31, 2019.Patients had a mean ± SD age of 64 ± 12 years, 14% were women, and 28% were African American. The treatment groups were balanced with regard to 87 baseline characteristics. There were 3 long QT syndrome events (0.03%), 2 of which occurred in patients receiving HCQ. Of the 56 arrhythmia-related hospitalizations (0.63%), 30 occurred in patients in the HCQ group (hazard ratio [HR] associated with HCQ 1.16 [95% confidence interval (95% CI) 0.68-1.95]). All-cause mortality occurred in 144 (3.25%) and 136 (3.07%) of the patients in the HCQ and non-HCQ groups, respectively (HR associated with HCQ 1.06 [95% CI, 0.84-1.34]). During the first 30 days of follow-up, there were no long QT syndrome events, 2 arrhythmia-related hospitalizations (none in the HCQ group), and 13 deaths (6 in the HCQ group).Our findings indicate that the incidence of long QT syndrome and arrhythmia-related hospitalization is low in patients with RA during the first year after the initiation of HCQ or another nonbiologic DMARD. We found no evidence that HCQ therapy is associated with a higher risk of adverse cardiovascular events or death.
Perspectives of US General Surgery Program Directors on Cultural and Fiscal Barriers to Maternity Leave and Postpartum Support During Surgical Training
Authors: Manuel Castillo-Angeles, Douglas S. Smink, Erika L. Rangel
Journal: JAMA Surgery (2021)

Although pregnancy during surgical residency is increasingly common, studies of surgical residents have identified challenges associated with pregnancy and motherhood. These include perceptions of different maternity leave policies among institutions, lack of mentorship, stigma, and desire for greater lactation support.To describe the perspective and experience of US surgical program directors regarding maternity leave and postpartum support for surgical residents.This qualitative study included surgical program directors of US general surgery residency programs who were selected using purposive-stratified, criterion-based sampling. Transcripts were collected from semi-structured interviews, which were audio-recorded and transcribed verbatim, from October 21, 2018, to June 1, 2019.Maternity leave and postpartum support.Perspectives of program directors regarding maternity leave and postpartum support were categorized into common themes identified using content analysis.A total of 40 US general surgical programs directors (28 [70.0%] male; mean [SD] age, 49.7 [6.8] years) were interviewed, of whom 36 (90.0%) were from university-based programs. All reported having maternity leave policies allowing a duration of leave of 6 weeks or longer. Analysis of program director interviews identified 5 themes: (1) residents are reluctant to extend training despite being offered multiple leave options; (2) childbearing negatively impacts the quality of work of certain residents; (3) lack of formal lactation policies creates practical challenges in supporting residents who are nursing; (4) resentment from coresidents who are asked to provide maternity leave coverage varies based on the prepregnancy reputation of the resident on leave; and (5) lack of salary support limits the practicality of extended leave options. Complex interpersonal issues affected residents differently, including stigma, reluctance to change established surgical training patterns, and challenges with work-life balance.This qualitative study found that sociopolitical issues within surgical training culture and fiscal constraints created obstacles against program directors supporting pregnant residents. These findings suggest that a multidimensional approach to supporting residents through written maternity and lactation policies, structured mentorship and coaching programs, and efforts by leadership to enforce family priorities is needed to promote a surgical culture that normalizes pregnancy and motherhood during training.
Abstract 16076: Elevated Body Mass Index and Blood Pressure Among Male High-School American Style Football Athletes
Authors: Prashant Rao, Drew Johnson, Abhinav Nair, Max Weiss, David Shipon
Journal: Circulation (2020)

Introduction: The impact of American Style Football (ASF) participation on cardiovascular health is unclear. Early-life weight gain among ASF athletes is common and is associated with risk of multiple later-life health afflictions. Despite the popularity of ASF participation among the youth, a rigorous comparison of the cardiovascular health profiles between ASF and non-ASF athletes at the high-school level has not been undertaken. We performed an observational cross-sectional study comparing the body mass index and blood pressures of ASF and non-ASF high-school athletes. Methods: Between October 2012 to November 2018 we performed voluntary cardiac screens including height, weight and blood pressure among predominantly high-school students. Inclusion criteria included the following: male sex; &gt;10 hours of exercise per week; single-sport athlete; age &gt;14 years old. Of the 6973 young individuals who underwent screening, 508 athletes were included in the analyzed data. Results: ASF athletes represented 18% of all high-school athletes. The mean age of ASF and non-ASF athletes was 18.5 and 18.0 years, respectively. BMI was higher in ASF athletes compared to non-ASF participating athletes (26.9 vs 21.2 p&lt;0.0001). There was a higher prevalence of class I and class II obesity among ASF athletes (class I obesity: 15% vs 1%; class II obesity: 10% vs 1%, p&lt;0.0001 for each). ASF athletes had an increased systolic (SBP) and diastolic blood pressure (DBP) compared to non-ASF participating athletes (SBP: 121 vs 114 p&lt;0.0001; DBP: 73 vs 70 p=0.0028). Among all athletes, there was a positive correlation between blood pressure and BMI (SBP: R=0.4149, DBP: R=0.2076, p&lt;0.0001 for each). Conclusions: High-school athletes that participate in ASF have a higher BMI, prevalence of obesity and blood pressure compared to their non-ASF counterparts. It is important to screen young ASF athletes for obesity and hypertension in order to optimize cardiovascular health at an early age.
Abstract 12916: Outcomes of Magnetic Resonance Imaging in Patients With Pacemakers/ICDs and Fractured or Abandoned Leads
Authors: Mark Greenhill, Paul Kang, Wilber Su, Michael Zawaneh, Peter Weiss, Sameul Unzek, Michael Morris
Journal: Circulation (2020)

Introduction: Current guidelines exclude patients with fractured or abandoned leads from MRI scanning due to possible safety concerns. In vitro, the configuration of fractured or abandoned leads impacts lead tip heating during MRI. This study examined the clinical impact of lead length, lead location, and lead shape on patient outcomes in patients with pacemakers/ICDs and fractured or abandoned leads undergoing MRI. Methods: Single center retrospective review of patients with pacemakers/ICDs and fractured or abandoned leads undergoing clinically indicated MRI from 7/2016 through 3/2020. Results: 58 patients with 68 abandoned/fractured leads underwent 112 MRI scans at 1.5T. The average age was 71.8 +/- 13.7 years with 22 (37%) female. Average MRI duration was 32.6 +/- 17 min. There were no significant changes in function of the intact leads or generator battery life after MRI. 58 leads were abandoned and 10 leads were fractured, including 52 pacemaker leads, 12 ICD leads, and 4 epicardial leads. Patients with abandoned leads had significantly longer lead length compared to those with fractured leads (58cm vs 6.8cm, p&lt;0.01), more often had a "c" shape lead configuration on chest xray (p&lt;0.01), and were more likely to terminate in the right ventricle (p&lt;0.01). Patients with fractured leads more often had a vertical (p&lt;0.01), horizontal (p&lt;0.01), or "r" shaped (p=0.05) configuration on chest xray, and lead fragments more often terminated in the left chest wall (p&lt;0.01). There were no adverse clinical events during MRI in any patient. Conclusions: In this study of patients with 68 abandoned/fractured leads undergoing 112 MRIs, neither lead length, lead location, nor lead shape was associated with adverse outcomes. In vitro studies suggesting that the configuration of abandoned/fractured leads can cause patient harm during MRI does not translate to clinical events. Future studies should further assess the safety of MRI scanning in patients with abandoned/fractured leads.
Abstract 16674: Smoking, Its Cessation, and Future Risk of Peripheral Artery Disease
Authors: Ning Ding, Yingying Sang, Shoshana H Ballew, Corey A Kalbaugh, Maya J Salameh, Michael J Blaha, Matthew A Allison, Gerardo Heiss, Elizabeth Selvin, Josef Coresh, Kunihiro Matsushita
Journal: Circulation (2017)

Introduction: Although smoking is a potent risk factor for peripheral artery disease (PAD), few studies have comprehensively evaluated the prospective association of smoking parameters (duration, i...
Abstract 15779: Unfavorable Social Determinants of Health Profile and Financial Toxicity From Healthcare in Atherosclerotic Cardiovascular Disease
Authors: Javier Valero Elizondo, Rohan Khera, Ramzi Dudum, Isaac Acquah, Adnan Hyder, Julia Andrieni, Garima Sharma, Michael J Blaha, Salim S Virani, Ron Blankstein, Miguel Cainzos Achirica, Khurram Nasir
Journal: Circulation (2020)

Introduction: Healthcare expenses for atherosclerotic cardiovascular disease (ASCVD) are associated with substantial financial toxicity (FT). Whether certain social determinants of health (SDOH) portend an increased risk of FT in ASCVD is critical to refine care processes that may be most amenable to interventions. Methods: Using National Health Interview Survey (2013-17), we assessed patients with self-reported ASCVD. We identified 35 discrete SDOH items, rated as favorable/unfavorable, across 6 domains: economic stability, education, food access, neighborhood conditions, social context, and health systems. To capture the cumulative effect of SDOH, an aggregate score was computed as their sum, and divided into quartiles, the highest quartile containing the most unfavorable scores. FT included presence of: difficulty paying medical bills/inability to pay them at all, and/or delayed/foregone care due to cost, and/or cost-related medication non-adherence. Results: Of 164,696 surveyed adults, of which 15,758 (weighted: 8%) reported ASCVD. Mean (SE) age-adjusted SDOH risk scores among ASCVD vs non-ASCVD patients were 11.8 (0.12) vs 9.5 (0.03), respectively. Among individuals with ASCVD, age-adjusted prevalence of any FT was directly proportional to SDOH aggregate scores, with step-wise increases noted. Prevalence of ≥ 2 FT factors among SDOH quartiles 1 st vs 4 th was 8% vs 50% among non-elderly (&lt; 65), and 2% vs 35% among elderly adults with ASCVD, respectively (Figure). Further, in adjusted models, patients in the most unfavorable quartile for SDOH had an 8-fold higher likelihood of FT compared to those in the most favorable group. Conclusions: Among ASCVD patients, a higher number of unfavorable SDOH features is strongly associated with the presence of FT, further calling for the development of interventions to alleviate FT among those with unfavorable SDOH profiles.