Citations

Abstract Background The ACC/AHA Pooled Cohort Equation (PCE) for atherosclerotic cardiovascular disease (ASCVD) has been recommended as the initial step in cardiovascular risk assessment. The sensitivity of this tool to detect those who will develop ASCVD within 10-years, while considering age and sex groups, has not been extensively studied. Methods Using the Rochester Epidemiology Project (REP) we evaluated a community-based cohort of consecutive patients that sought primary care in Olmsted County, MN, between the years 1998–2000 and were followed up through March 1st 2016. Inclusion criteria were ages 40–79 and complete data to calculate the PCE. We excluded those with known ASCVD, atrial fibrillation or heart failure. Criteria were similar to those used to derive the PCE. Events were validated in duplicate and included fatal and non-fatal myocardial infarction and ischemic stroke. Patient information was ascertained using the record linkage system of the REP. Follow-up was truncated at 10 years. We assessed the ASCVD predicted risk (categorized as low <5%, intermediate 5–9.9%, high 10–19.9%, and very high ≥20% risk) at baseline, in subjects having an ASCVD event within 10-years in the community across age (<65 years) and sex categories. We also categorized ideal cardiovascular health as ≥4 metrics [non-smoker, body mass index <25 kg/m2, and not having of elevated blood pressure (≥130/80 mmHg), LDL cholesterol (>100 mg/dL), or fasting blood glucose (>100 mg/dL), in the absence of a medical diagnosis or treatment]. Results We included 30,042 adults, mean ± SD age 48.5±12.2 years, 54% women, with a median follow-up of 16.5±5.3 years. There were 1,555 ASCVD events (5.2%) at 10 years of follow-up. The performance of the PCE was similar to what was described in the original report (0.78 vs 0.79). Overall, among those who suffered an ASCVD, 54% of women and 41% of men were not high risk as predicted by PCE (Figure 1A). Most women (73%) <65 years of age would had been considered low risk within 10-years before the event, and only 10% would have been considered to be high risks (Figure 1B). Nonetheless, women <65 years who had an ASCVD event and low 10-year predicted ASCVD risk by PCE were less likely to have ideal cardiovascular health [55 (0.40%) vs 3884 (28.39%), p-value<0.0001], when compared to women in the low risk category without an event. Conclusion The PCE fails to identify most women who will develop an ASCVD event, particularly women <65 years of age. These results underscore the importance of using additional information when estimating ASCVD risk among women and the need for better cardiovascular risk prediction tools. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Mayo Clinic

Impaired AhR ligand production by the gut microbiota decreases AhR pathway activation, promoting inflammation in celiac disease.

At the beginning of the SARS Co V2 (COVID-19) pandemic, women worldwide represented the majority of health care workers. As part of the fight against the pandemic, women health care workers became a part of the significant frontline response. This led to unique challenges that affected women physicians as well as the women patients they were taking care of. The American College of Cardiology Women in Cardiology International Working Group set up a webinar to discuss the challenges being faced by women physicians and women patients in various parts of the world and look towards finding possible solutions for these issues in a webinar themed ?WIC Global Perspectives: COVID-19.?

Abstract The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine, in a 3- to 4-year recurring cycle of topics. These topics will be presented at the 2020 International Conference. Below is the adult critical care medicine core including complications of chemotherapy, acute-on-chronic liver failure, alcohol withdrawal syndrome, mechanical circulatory support, direct oral anticoagulants, upper gastrointestinal hemorrhage, and vasopressor selection.

Abstract The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine in a 3- to 4-year recurring cycle of topics. The topics of the 2020 Pulmonary Core Curriculum include pulmonary vascular disease (submassive pulmonary embolism, chronic thromboembolic pulmonary hypertension, and pulmonary hypertension) and pulmonary infections (community-acquired pneumonia, pulmonary nontuberculous mycobacteria, opportunistic infections in immunocompromised hosts, and coronavirus disease [COVID-19]).

Chloroethylagelastatin A (CEAA) is an analogue of agelastatin A (AA), a natural alkaloid derived from a marine sponge. It is under development for therapeutic use against brain tumors as it has excellent central nervous system (CNS) penetration and pre-clinical therapeutic activity against brain tumors. Recently, AA was shown to inhibit protein synthesis by binding to the ribosomal A-site. In this study, we developed a novel virtual screening platform to perform a comprehensive screening of various AA analogues showing that AA analogues with proven therapeutic activity including CEAA have significant ribosomal binding capacity whereas therapeutically inactive analogues show poor ribosomal binding and revealing structural fingerprint features essential for drug-ribosome interactions. In particular, CEAA was found to have greater ribosomal binding capacity than AA. Biological tests showed that CEAA binds the ribosome and contributes to protein synthesis inhibition. Our findings suggest that CEAA may possess ribosomal inhibitor activity and that our virtual screening platform may be a useful tool in discovery and development of novel ribosomal inhibitors.

Abstract Background Black race is associated with worse outcomes in early breast cancer. We evaluated clinicopathologic characteristics, the 21-gene recurrence score (RS), treatment delivered, and clinical outcomes by race and ethnicity among women who participated in the Trial Assigning Individualized Options for Treatment. Methods The association between clinical outcomes and race (White, Black, Asian, other or unknown) and ethnicity (Hispanic vs non-Hispanic) was examined using proportional hazards models. All P values are 2-sided. Results Of 9719 eligible women with hormone receptor–positive, HER2-negative, node-negative breast cancer, there were 8189 (84.3%) Whites, 693 (7.1%) Blacks, 405 (4.2%) Asians, and 432 (4.4%) with other or unknown race. Regarding ethnicity, 889 (9.1%) were Hispanic. There were no substantial differences in RS or ESR1, PGR, or HER2 RNA expression by race or ethnicity. After adjustment for other covariates, compared with White race, Black race was associated with higher distant recurrence rates (hazard ratio [HR] = 1.60, 95% confidence intervals [CI] = 1.07 to 2.41) and worse overall survival in the RS 11-25 cohort (HR = 1.51, 95% CI = 1.06 to 2.15) and entire population (HR = 1.41, 95% CI = 1.05 to 1.90). Hispanic ethnicity and Asian race were associated with better outcomes. There was no evidence of chemotherapy benefit for any racial or ethnic group in those with a RS of 11-25. Conclusions Black women had worse clinical outcomes despite similar 21-gene assay RS results and comparable systemic therapy in the Trial Assigning Individualized Options for Treatment. Similar to Whites, Black women did not benefit from adjuvant chemotherapy if the 21-gene RS was 11-25. Further research is required to elucidate the basis for this racial disparity in prognosis.

AbstractBackgroundAlthough coronavirus disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data describing agents with potential antiviral activity continue to expand such that updated guidance is needed regarding use of these agents in children.MethodsA panel of pediatric infectious diseases physicians and pharmacists from 20 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of the best available evidence and expert opinion.ResultsGiven the typically mild course of COVID-19 in children, supportive care alone is suggested for most cases. For children with severe illness, defined as a supplemental oxygen requirement without need for noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), remdesivir is suggested, preferably as part of a clinical trial if available. Remdesivir should also be considered for critically ill children requiring invasive or noninvasive mechanical ventilation or ECMO. A duration of 5 days is appropriate for most patients. The panel recommends against the use of hydroxychloroquine or lopinavir-ritonavir (or other protease inhibitors) for COVID-19 in children.ConclusionsAntiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For children with severe or critical disease, this guidance offers an approach for decision-making regarding use of remdesivir.

8008 Background: Morphology remains the best biomarker for chemotherapy selection in NSCLC. Both bevacizumab and pemetrexed (in first line) are FDA indicated for non-SC histology only, making precise diagnosis key, although data are few on the reproducibility of their categorization. The standard of care, consensus-based World Health Organization diagnostic classification system, Ed. 4 (WHOC) includes 44 diagnostic categories (DC), does not include immunohistochemical (IHC) data, and is not independently validated. In this study, we estimate the reproducibility of SC versus non-SC classification to be only moderately precise. Methods: Pathologists (P) assigned WHOC diagnoses to virtual H&E slides from an incident surgical cohort of 96 primary lung tumors. At a power of 80% we estimated 24 P reviewing 48 slides each would allow for a reproducibility measure in the clinically useful range kappa=0.7, standard error=0.09. In addition to the 44 DC, we also considered the reproducibility of a simplified 10 category system and a chemotherapy-directed 2 class system. Results: 12 self-identified “lung experts” (E) and 12 community (C) P scored slides based on the 44 possible WHOC DC totaling 222 pathologist-pairs and 7130 slides-pairs. P rated confidence in their choices as: high 53%, somewhat 38%, and not confident 8%. 92% of slides were rated as having sufficient quality. Distribution of DC included SC 30% and adenocarcinoma 36%. Conclusions: To our knowledge this is the largest study ever performed of the WHOC, the only one to consider all 44 DC and to distinguish E vs C P. Although this model tests the reproducibility of the WHOC, not clinical lung cancer diagnoses, it shows that reproducible diagnosis of SC based on H&E morphology alone is inadequate. In the era of histology guided therapy, it highlights the need for strict diagnostic criteria and confirmatory IHC stains in the diagnosis of SC. [Table: see text] No significant financial relationships to disclose.