tbuckley/cabot-search huggingface dataset:
Abstract 12605: Brain Metabolic Activity Within Regions Involved in Stress Perception Associates Directly With Arterial Inflammation and Inversely With Aortic Distensibility in Psoriasis
Authors: Tsion M Aberra, Abhishek Chaturvedi, Joseph B Lerman, Amit K Dey, Parag Shukla, Aditya A Joshi, Justin A Rodante, Joanna I Silverman, Qimin Ng, Heather L Teague, Mark A Ahlman, David A Bluemke, Martin P Playford, Ahmed A Tawakol, Nehal N Mehta
Journal: Circulation (2016)

Introduction: Psychological stress and depression are linked to increased cardiovascular (CV) events in the general population and in psoriasis (PSO), a chronic inflammatory disease that increases CV risk. 18-FDG-PET/CT enables quantification of metabolic activity of the amygdala, a neural tissue critically involved in the pathobiology of stress and depression. In individuals without chronic inflammatory diseases, amygdalar activity (AmygAct) associates with greater vascular inflammation (VI) and CV events. However, it is not known whether PSO maintains this relationship with VI and whether AmygAct associates with other measures of subclinical CVD. Hypothesis: In PSO, AmygAct: 1) is higher in individuals who report depression/anxiety, and 2) associates with greater VI and decreased aortic distensibility. Methods: Subjects with PSO (n=82) completed a questionnaire at baseline, reporting psychiatric history and were placed into two groups accordingly: patients with depression/anxiety and age and sex matched controls with no psychiatric diagnoses. AmygAct was quantified using 18-FDG PET/CT by an analyst blinded to clinical data. Mean standardized uptake values (SUV) for the left amygdala were corrected for background brain activity. VI was quantified as a ratio of aortic to blood background SUV. Aortic distensibility was measured using phase contrast MRI. Results: Subjects had a mean age of 49.2 years, were 49% males, and had a median Framingham risk score of 3. Patients with a history of depression and/or anxiety had significantly higher AmygAct than those without (mean±SEM 0.85±0.01 vs. 0.81±0.01; p=0.01). AmygAct correlated with VI (β= 0.26, p=0.02) as well as aortic distensibility (β= -0.50, p&lt;0.001). Moreover, AmygAct remained associated with aortic distensibility after adjustment for Framingham risk score and hypertension (β= -0.37, p=0.007). Conclusions: Metabolic activity within neural tissues involved in stress perception significantly associates with indices of atherosclerotic disease in PSO. Future studies should further evaluate the mechanisms linking neural and atherosclerotic tissues in chronic inflammatory conditions such as PSO, and probe whether perturbing this mechanism may reduce the burden of atherosclerosis.
A pilot study of adjuvant bevacizumab after neoadjuvant chemotherapy for high-risk breast cancer
Authors: E. L. Mayer, K. D. Miller, H. S. Rugo, J. M. Peppercorn, L. A. Carey, N. Ryabin, E. P. Winer, H. J. Burstein
Journal: Journal of Clinical Oncology (2007)

561 Background: Patients with residual breast cancer after neoadjuvant chemotherapy are at increased risk of recurrence and may have chemotherapy-resistant disease. We sought to explore the role of novel antiangiogenic therapy in this patient population. Methods: This phase II trial evaluated the feasibility and toxicity of adjuvant antiangiogenic therapy. Eligible patients had stage II-III breast cancer with residual invasive carcinoma at surgery following anthracycline-containing neoadjuvant chemotherapy. Treatment consisted of bevacizumab 15 mg/kg given every three weeks for one year, starting no less than 1 month after surgery or 2 weeks after radiation. Concurrent endocrine and/or trastuzumab therapy was allowed. The primary endpoint was feasibility and tolerability of single agent bevacizumab. Results: 40 patients were treated with bevacizumab monotherapy. Median age was 50 years, 45% were stage III, 58% were hormone receptor positive, and 8% were HER2+. There were 11 delays in treatment administration (average delay = 7.2 days). To date, patients are on average through 10.4 of 17 planned cycles of therapy, with 3 patients completing treatment and 3 patients with tumor recurrence on study. Treatment-related toxicities include mild arthralgias (50%), headache (50%), epistaxis (20%), and hypertension (23%). One patient experienced reversible posterior leukencephalopathy related to hypertension, one patient had GI bleeding, and 4 subjects voluntarily removed themselves from the protocol. No cardiac dysfunction has been observed. Definitive feasibility/safety data and preliminary correlative studies will be available by June 2007. Conclusions: Adjuvant bevacizumab after neoadjuvant chemotherapy appears tolerable and feasible with side effects including hypertension, arthralgias, epistaxis, and headache. Three recurrences within a median follow-up of 7.5 months underscore the need for novel treatments among such patients. Ongoing trials are evaluating bevacizumab with oral chemotherapy. [Table: see text]
Abstract P198: Connected Health Remote Monitoring in Atrial Fibrillation Care Management
Authors: Robert Scales, Kathryn Lew, Colin Parker, Aasaf Raad, Steven Lester
Journal: Circulation (2020)

Background: Avoiding early hospital readmission after a diagnosis of atrial fibrillation (AF) lowers healthcare costs. Purpose: This investigation pilot tested the process of using a Connected Health (CH) communication platform in AF care management. Subjects: A self-selected group of patients (n=18, 56% male, mean age=69 years, SD =12.6) diagnosed with hemodynamically stable AF and an uncontrolled ventricular response with heart rates &gt; 110 bpm were recruited. MethodS: Eligibility criteria included a recent AF related emergency department or outpatient clinic visit and the new prescription of a rate control medication. This included AV node modifying medications (either a beta blocker or nondihydropyradine calcium channel blocker) at a starting dose determined by the supervising physician. A care management team (CMT) coordinated by a nurse practitioner provided individualized telephone medical management with no planned clinical visits during a period of early recovery. Patients were equipped with the AliveCor TM Kardia electrocardiogram (ECG) home monitoring device and a supporting mobile device application. Patients returned home with medical guidance from the CMT and ECG recording instructions. Heart rate and rhythm were monitored remotely by the NP and the medication dose was adjusted to reach a target resting heart rate &lt;110 bpm. Patients were managed for 3-weeks before being discharged back to primary care or outpatient cardiology for consideration of a rate versus rhythm control strategy if spontaneous restoration of sinus rhythm had not occurred. ResultS: Patients recorded an average of 50 ( SD =40.0) ECG tracings with a mean of 13 ( SD =3.79) related CMT telephone contacts. The mean resting heart rate was significantly lower ( p &lt;0.05) at the completion of the intervention (72.9 bpm, SD =17.31) compared to baseline (102.3 bpm, SD =27.17). All of the AF patients achieved adequate heart rate control or spontaneously returned to sinus rhythm. However, 4 patients (22%) required a related emergency room visit and unplanned hospitalization. Conclusion: In this small feasibility study, an electronic healthcare device (biosensor) paired with a mobile-heath application provided a practical remote monitoring communication platform to support tele-management, but the intervention did not prevent hospital readmission. Future Directions: Further research is needed to identify factors that will improve the process of applying CH to AF care management.
Reply to Kobayashi <i>et al.</i>: Too Premature to Deny the Potential of Thrombomodulin Alfa in Idiopathic Pulmonary Fibrosis
Authors: Yasuhiro Kondoh, Arata Azuma, Jun Tagawa, Natsuki Yamamori, Sakae Homma
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
The mycobiota of the human body: a spark can start a prairie fire
Authors: Di Zhang, Ying Wang, Sunan Shen, Yayi Hou, Yugen Chen, Tingting Wang
Journal: Gut Microbes (2020)

Mycobiota are inseparable from human health, shaking up the unique position held by bacteria among microorganisms. What is surprising is that this seemingly small species can trigger huge changes in the human body. Dysbiosis and invasion of mycobiota are confirmed to cause disease in different parts of the body. Meanwhile, our body also produces corresponding immune changes upon mycobiota infection. Several recent studies have made a connection between intestinal mycobiota and the human immune system. In this review, we focus on questions related to mycobiota, starting with an introduction of select species, then we summarize the typical diseases caused by mycobiota in different parts of the human body. Moreover, we constructed a framework for the human anti-fungal immune system based on genetics and immunology. Finally, the progression of fungal detection methods is also reviewed.
CD8+ T Cells Impact Rising PSA in Biochemically Relapsed Cancer Patients Using Immunotherapy Targeting Tumor-Associated Antigens
Authors: Neal D. Shore, Matthew P. Morrow, Trevor McMullan, Kimberly A. Kraynyak, Albert Sylvester, Khamal Bhatt, Jocelyn Cheung, Jean D. Boyer, Li Liu, Brian Sacchetta, Samantha Rosencranz, Elizabeth I. Heath, Luke Nordquist, Heather H. Cheng, Scott T. Tagawa, Leonard J. Appleman, Ronald Tutrone, Jorge A. Garcia, Young E. Whang, W. Kevin Kelly, David B. Weiner, Mark L. Bagarazzi, Jeffrey M. Skolnik
Journal: Molecular Therapy (2020)

The management of men with prostate cancer (PCa) with biochemical recurrence following local definitive therapy remains controversial. Early use of androgen deprivation therapy (ADT) leads to significant side effects. Developing an alternative, clinically effective, and well-tolerated therapy remains an unmet clinical need. INO-5150 is a synthetic DNA therapy that includes plasmids encoding for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA), and INO-9012 is a synthetic DNA plasmid encoding for interleukin-12 (IL-12). This phase 1/2, open-label, multi-center study enrolled men with PCa with rising PSA after surgery and/or radiation therapy. Patients were enrolled into one of four treatment arms: arm A, 2 mg of INO-5150; arm B, 8.5 mg of INO-5150; arm C, 2 mg of INO-5150 + 1 mg of INO-9012; and arm D, 8.5 mg of INO-5150 + 1 mg of INO-9012. Patients received study drug with electroporation on day 0 and on weeks 3, 12, and 24, and they were followed for up to 72 weeks. Sixty-two patients were enrolled. Treatment was well tolerated. 81% (50/62) of patients completed all visits. 85% (53/62) remained progression-free at 72 weeks. PSA doubling time (PSADT) was increased when assessed in patients with day 0 PSADT ≤12 months. Immunogenicity was observed in 76% (47/62) of patients by multiple assessments. Analysis indicated that CD38 and perforin co-positive CD8 T cell frequency correlated with attenuated PSA rise (p = 0.05, n = 50).
Abstract P144: The Modification Effect of Genetic Variants on the Association Between Dietary Red Meat Intake and Telomere Length
Authors: Xuling Chang, Rajkumar Dorajoo, Ye Sun, Ling Wang, Renwei Wang, Yechiel Friedlander, Jianjun Liu, Chiea Chuen Khor, Jian-Min Yuan, Woon-Puay Koh, Chew-Kiat Heng
Journal: Circulation (2020)

Background: Telomeres are repetitive nucleotide sequences (TTAGGG) combined with associated protein at the end of eukaryote chromosomes. They shorten with each cell division and thus can act as a biomarker of cellular aging. Many factors can influence telomere length, including nutrition, physical activity and other lifestyle factors. However, the effects of diet, such as consumption of red meat on telomere length, is controversial. In East-Asians, the effect of red meat on telomeres as well as the modification effect of red meat on the association between genetic variants and telomeres are largely unknown. Method: Study included 20,011 individuals with complete information. Relative telomere length was determined using monochrome multiplex quantitative PCR (qPCR) and expressed as T/S ratio from 20,011 participants of the prospective Singapore Chinese Health Study (SCHS) Dietary information was collected using a semi-quantitative food frequency questionnaire. Red meat consumption was first adjusted for total energy intake by linear regression and then dichotomized based on median value. Telomere length was standardised by z score transformation. Linear regression was used to test the association between telomere length and red meat consumption. Interaction analyses were performed by introducing the interaction term (red meat x SNP) in the same regression model with adjustment for age, gender, total energy intake and population structure as covariates. Result: Higher intake of red meat was significantly associated with longer telomere length in SCHS (β = 0.027, se = 0.013, p = 0.042). Red meat intake can modify the association between rs7536250 and telomere length (β = -0.170, se = 0.025, p int = 1.35 х 10 -11 ). Rs7536250 was intergenic and found to affect the expression level of several genes through expression quantitative trait loci (eQTL), some of which are known to be involved in T-cell activation, apoptosis and programmed cell death. Conclusion: The association between red meat intake and telomeres is consistent with some previous findings. We also found that genetic variant can modify the association between dietary red meat intake and telomere length.
Abstract P236: Breastfeeding and Drug Free Moms and Babies Project: Comparing Rates in a Rural Appalachia Project to Project Watch to Support Healthy Baby Outcomes
Authors: Christa LILLY, Amna Umer, Janine Breyel, Candice Hamilton, Collin C John
Journal: Circulation (2020)

Breastfeeding is linked to improved cardiovascular health for both child and mother; however, many hospitals do not encourage or provide support for breastfeeding while either in the hospital or after delivery. This is particular true of mothers with substance use disorder (SUD) more generally or with opioid use disorder (OUD) more specifically. The Drug-Free Moms and Babies Project (DFMB) program was designed to develop and evaluate programs that provide treatment and recovery services for pregnant and postpartum women with SUD; data is now available for 2018 and up to October 2019. Project WATCH collects data on all births in West Virginia (WV) and includes questions about breastfeeding intent and actual breastfeeding practices. A special focus for both programs includes encouraging or assessing breastfeeding in WV, which ranked 46 th in the nation for ever breastfeeding in 2015. There were 688 pregnant women in DFMB 2018-2019 with information on breastfeeding intent; at program entry, 54.8% intended to breastfeed. Relative to all births in WV in 2018 (Project WATCH data; N=18177), 57.4% intended to exclusively breastfeed. Among all births with intrauterine substance exposure (IUSE) in 2018 (N=2558), 31% intended to exclusively breastfeed. Of the 688 in the DFMB program, 528 completed the program through delivery and had breastfeeding information. Of those, 225 (42.6%) actually breastfed after birth, and 80.6% were given the opportunity to breastfeed before leaving the hospital. For actual breastfeeding rates among all births in WV (Project WATCH), 37.4% exclusively breastfed before hospital discharge, and among births with IUSE, 32.0% exclusively breastfed. We also examined breastfeeding rates among those infants born with NAS in the DFMB program (N=220, 42.8%). Of these women, 49.7% intended to breastfeed, 37.4% breastfed after birth, and 73.5% were given the opportunity to breastfeed before hospital discharge. Among all 2018 WV NAS births (N=901), actual breastfeeding rate was 9.1%. Results suggest DFMB programs improve breastfeeding rates when compared against all births in the state, and among births with IUSE. The program continues to intervene with this high-risk group to improve breastfeeding rates, which we believe will later impact cardiovascular health for both mothers and babies.
Survival following recurrence in patients with adjuvant colon cancer: Findings from the 20,800-patient ACCENT dataset
Authors: M. J. O’Connell
Journal: Journal of Clinical Oncology (2007)

4009 Purpose: To examine 4 possible prognostic factors in patients (pts) with recurrent (rec) stage II and III colon cancer: time from randomization to rec (&lt; 1 yr, 1–2 yrs 2–3 yrs 3–4 yrs, 4+ yrs), initial stage (II vs III), initial adjuvant treatment (adj rx) (5-FU based vs no rx control), and era pt entered onto study (1978–1985, 1986–1992, 1993–1999). Methods: The Adjuvant Colon Cancer Endpoints (ACCENT) dataset, including individual pt data from 18 trials and over 20,800 pts testing 5-FU based adj rx for pts with stage II and III colon cancer, was analyzed using univariate and multivariate Cox proportional hazards models, stratified by study. The QUASAR trial (Lancet, 2000) was excluded due to non protocol specified follow-up for rec. No data was available on rx subsequent to rec, or tumor characteristics at time of rec. Results: 5,713 of 17,381 (32.9%) of pts experienced rec. Median survival following rec was 13.4 months. Primary results from univariate models are shown in the table . Time from randomization to rec was highly prognostic of survival following rec (p&lt;0.0001); this result was primarily driven by pts with initial stage III disease. Longer survival following rec was also seen in pts with initial stage II vs III disease (p&lt;0.0001), with a 15% 6 year OS in initial stage II pts, pts entered more recently onto trials (p&lt; 0.0001), and pts initially treated with surgery alone vs 5-FU adj rx (p=0.0005). All relationships were maintained in multivariate models. Conclusions: Time from initial rx and initial stage are important prognostic factors in pts with rec colon cancer. Survival following rec increased modestly from 1980–1995 possibly due to improvements in surgery, chemotherapy, supportive care, or unknown selection effects. Pts who rec following adj rx have poorer prognosis than those untreated, which may be a selection effect (only more aggressive tumors escape adj rx), or a sensitivity effect (those without adj rx retain sensitivity to 5-FU in the rec setting). [Table: see text] No significant financial relationships to disclose.
Covid-19: US health department staff sent to meet citizens returning from China weren’t protected, claims whistleblower
Authors: Owen Dyer
Journal: BMJ (2020)

A senior employee of the US Department of Health and Human Services has filed a whistleblower complaint alleging that untrained staff were sent without proper protective equipment to meet the first Americans evacuated from Wuhan, China.

The government employees greeted the returning Americans in an aircraft hangar, the whistleblower reported in a formal complaint. They later saw them again to hand out coloured ribbons for identification and a third time to give them room keys for their quarantine at US airbases.

But some of the employees were disconcerted when they saw staff from the US Centers for Disease Control working alongside them in “full gown, gloves, and hazmat attire,” says the complaint, which has been seen by the Washington Post .

The health department workers were drawn from the Administration for Children and Families (ACF), used normally to help disaster victims access …
Abstract MP44: Nitrite Generating Capacity Assessed Through the Oral Microbial Metagenome is Associated With Cardiometabolic Risk
Authors: Bruno Bohn, Charlene Goh, Lisa Marotz, Rebecca L Molinsky, Sumith Roy, Bruce Paster, Rob Knight, Michael Rosenbaum, Moise Desvarieux, Panos N Papapanou, David R Jacobs, Paolo C Colombo, Ryan Demmer
Journal: Circulation (2020)

Introduction: Nitric oxide (NO) is important for cardiometabolic health. The enterosalivary nitrate-nitrite-NO pathway generates NO following oral microbiota-mediated production of salivary nitrite. We investigated the association between the abundance of genes in this pathway and cardiometabolic biomarkers. Hypothesis: Microbial genes favoring increased oral nitrite generation are associated with better cardiometabolic profile. Methods: We enrolled 784 diabetes-free adults in the Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS). Subgingival plaques were collected from 6-8 teeth/participant. 16S rRNA microbial genes (Illumina, MiSeq) were sequenced; PICRUSt2 estimated abundance of microbial genes in the nitrate-nitrite pathway associated with either nitrite generation or depletion. Gene abundance was summed within each group, and a ratio between nitrite generation to depletion (GDR) was calculated; higher levels suggest increased nitrite generating capacity. Systolic and diastolic blood pressure were measured and HbA1C, insulin, and glucose levels were determined in fasting blood. Z-scores were calculated for cardiometabolic biomarkers and averaged to form a cardiometabolic z-score (CMZ-score). Adjusted multivariable linear models were used to regress the CMZ-score and individual Z-scores on GDR. Results: Participants were 69% female and aged 19-58 years (mean=32±9). Mean CMZ-score was 0.00±0.7. Mean (range) GDR was 1.88 (0.22-7.84). Mean CMZ-scores (SE) across GDR quartiles were 0.17 (0.06), 0.01 (0.05), -0.04 (0.05), and -0.14 (0.05), p-value for trend=0.02. Linear regression coefficients summarizing associations between GDR and individual Z-scores (Table) show lower Z-score for systolic and diastolic blood pressure, HbA1C, and insulin levels in those with higher GDR. Conclusions: Increased capacity for nitrite production by oral bacteria, assessed through a metagenome estimation approach, is associated with lower levels of cardiometabolic risk.
Abstract P151: Race/ethnic Differences in Six Minute Walk Distance Among Older Adults: The Multi-ethnic Study of Atherosclerosis
Authors: Alain G Bertoni, Michael Bancks, Lenore Crago, Haiying Chen, R G Barr, Benjamin Smith, Sanjiv J Shah
Journal: Circulation (2020)

Introduction: Data about race/ethnic differences in functional capacity among U.S. minority groups is limited, although some studies suggest blacks have a shorter six minute walk distance (6MWD), a test of functional capacity. We measured 6MWD in the Multi-Ethnic Study of Atherosclerosis (MESA), and hypothesized that health behaviors, CVD risk factors, prevalent CVD, and pulmonary function may account for any race/ethnic differences observed. Methods: MESA enrolled 6814 adults aged 45-84 years free of clinical CVD during 2000-2002. During the 6 th examination (2016-2018) trained staff measured the distance (in meters) walked by participants who walked laps at their own pace for 6 minutes along a flat and marked 20 meter distance. Race/ethnicity, gender, and education level were ascertained at baseline; Exam 6 values for all other variables were used. Prevalent CVD was defined as having a previously adjudicated event (ischemic heart disease, stroke, or heart failure). The race/ethnicity-6MWD association was evaluated via general linear regression models. We included adjustment for age, sex, education, smoking, alcohol, height, waist circumference, self-reported health status, Kansas City Cardiomyopathy Questionnaire score, diabetes, systolic blood pressure (BP), total cholesterol, BP and cholesterol medication use, creatinine, and prevalent CVD (and FEV1 and FVC for those with spirometry data). Results: A 6MWD was obtained in 2,539 participants (mean age 73 years (range 59-96) 53% female, 41% white, 14% Chinese, 24% Black, and 22% Hispanic; 8% prevalent CVD). The observed 6MWD differed by race/ethnicity by 30-50 m (Table). Covariate adjustment reduced these differences modestly. In the subset (n=2138) with spirometry (Model 4), 6MWD remained different across race/ethnicity. Conclusions: Race/ethnic disparities in functional capacity in this diverse sample are not fully explained by differences in health behaviors, CVD risk factors, prevalent CVD, heart failure symptoms, or pulmonary function.