Impact of COVID-19 pandemic on physician-scientist trainees to faculty one year into the pandemic.

PURPOSE: Physician-scientists play a crucial role in advancing biomedical sciences. Proportionally fewer physicians are actively engaged in scientific pursuits, attributed to attrition in the training and retention pipeline. This national study evaluated the ongoing and longer-term impact of the COVID-19 pandemic on stress levels, research productivity, and optimism for physician-scientists at all levels of training. METHODS: A multi-institutional cross-sectional survey of medical students, graduate students, and residents/fellows/junior faculty (RFJF) was conducted from April to August 2021 to assess the impact of COVID-19 on individual stress, productivity, and optimism. Multivariate regression analyses were performed to identify associated variables and unsupervised variable clustering techniques were employed to identify highly correlated responses. RESULTS: A total 677 respondents completed the survey, representing different stages of physician-scientist training. Respondents report high levels of stress (medical students: 85%, graduate students: 63%, RFJF: 85%) attributed to impaired productivity concerns, concern about health of family and friends, impact on personal health and impairment in training or career development. Many cited impaired productivity (medical students: 65% graduate students: 79%, RFJF: 78%) associated with pandemic impacts on training, labs closures and loss of facility/resource access, and social isolation. Optimism levels were low (medical students: 37%, graduate students: 38% and RFJF: 39%) with females less likely to be optimistic and more likely to report concerns of long-term effects of COVID-19. Optimism about the future was correlated with not worrying about the long-term effects of COVID-19. Since the COVID-19 pandemic, all respondents reported increased prioritization of time with family/friends (67%) and personal health (62%) over career (25%) and research (24%). CONCLUSIONS: This national survey highlights the significant and protracted impact of the COVID-19 pandemic on stress levels, productivity, and optimism among physician-scientists and trainees. These findings underscore the urgent need for tailored support, including mental health, academic, and career development assistance for this biomedical workforce.

Characteristics, barriers, and career intentions of a national cohort of LGBTQ+ MD/PhD and DO/PhD trainees.

BACKGROUND: Lesbian, gay, bisexual, transgender, queer, non-binary, intersex, and/or asexual (LGBTQ+) individuals continue to suffer worse health outcomes compared to the general population. Data on LGBTQ+ individuals in medicine, particularly in medical training, remain sparse. National studies of LGBTQ+ students in MD/PhD and DO/PhD training programs have not been reported. METHODS: Trainees pursuing MD, DO, MD/PhD, and DO/PhD degrees at 32 nationally representative institutions completed a 70-item survey about their future career and anticipated challenges using an online survey tool from September 2012 to December 2014. There were 4,433 respondents to the survey. Of those, 2,837 completed the gender identity questions and 2,849 completed the sexual orientation questions. Completion of these questions was required for inclusion. Survey results were analyzed to examine differences between LGBTQ+ and non-LGBTQ+ medical and dual degree trainees. RESULTS: LGBTQ+ students were underrepresented among MD/PhD and DO/PhD trainees (8.70%) compared to the US population, though their representation was higher than among MD and DO trainees (5.20%). LGBTQ+ dual degree trainees endorsed the greatest interest in pursuing careers involving academic medicine, with varying career focuses including research, clinical duties, education, and advocacy. LGBTQ+ dual degree trainees prioritized opportunities in patient care, work-life balance, and research as the most important factors for their career selection. Importantly, a higher percentage of LGBTQ+ dual degree trainees (15.50%) identified sexual harassment as a past barrier to career advancement compared to their non-LGBTQ+ peers (8.27%). LGBTQ+ dual degree trainees were more likely to report having a mentor who advocated for them. CONCLUSIONS: LGBTQ+ physician scientist trainees remain under-represented and under-studied. It is vital that medical institutions devote more time and resources towards identifying and addressing the unique needs of this group in training. Training programs should be aware of the current and prior challenges faced by their LGBTQ+ dual degree trainees, work to overcome the unique barriers they face, highlight the strengths and unique perspectives they bring, and foster their professional growth and goals during and beyond their training.

The Role and Impact of Social Media in Cardio-oncology During the COVID-19 Pandemic.

PURPOSE OF REVIEW: To give an overview of the role of social media (SoMe) in cardio-oncology during the COVID-19 pandemic. RECENT FINDINGS: SoMe has been critical in fostering education, outreach, awareness, collaboration, dissemination of information, and advocacy in cardio-oncology. This has become increasingly evident during the COVID-19 pandemic, during which SoMe has helped share best practices, community, and research focused on the impact of COVID-19 in cardiology and hematology/oncology, with cardio-oncology at the interface of these two subspecialty fields. A strength of SoMe is the ability to amplify a message in real-time, globally, with minimal investment of resources. This has been particularly beneficial for the emerging field of cardio-hematology/cardio-oncology, a field focused on the interplay of cancer and cardiovascular disease. SoMe field especially during the COVID-19 pandemic. We illustrate how social media has supported innovation (including telemedicine), amplification of healthcare workers' voice, and illumination of pre-existing and continued health disparities within the field of cardio-oncology during the pandemic.

Gender disparities among medical students choosing to pursue careers in medical research: a secondary cross-sectional cohort analysis.

BACKGROUND: Though the proportion of women in medical schools has increased, gender disparities among those who pursue research careers still exists. In this study, we seek to better understand the main factors contributing to the existing gender disparities among medical students choosing to pursue careers in medical research. METHODS: A secondary cross-sectional cohort analysis of previously published data was conducted using a 70-item survey that was sent to 16,418 medical students at 32 academic medical centers, and was IRB exempt from the need for ethical approval at the University of Illinois at Chicago and the University of Pennsylvania. Data was collected from September 2012 to December 2014. Survey results were analyzed using chi-square tests and Cramer's V to determine gender differences in demographic characteristics (training stage, race/ethnicity, marital status, parental status, financial support, and parental career background), career sector choice, career content choice, specialty choice, foreseeable career obstacles, and perceptions about medical research careers. RESULTS: Female respondents were more likely to be enrolled in MD-only programs, while male respondents were more likely to be enrolled in MD/PhD programs. More male students selected academia as their first-choice career sector, while more female respondents selected hospitalist as their first-choice career sector. More female respondents identified patient care and opportunities for community service as their top career selection factors, while more male respondents identified research and teaching as their top career selection factors. Student loan burden, future compensation, and work/life balance were the most reported obstacles to pursuing a career in medical research. CONCLUSIONS: There are many factors from a medical student's perspective that may contribute to the existing gender disparities in pursuing a career in medical research. While much progress has been made in attracting nearly equal numbers of men and women to the field of medicine, active efforts to bridge the gap between men and women in medical research careers are needed.

Factors associated with underrepresented minority physician scientist trainee career choices.

BACKGROUND: Recently, there have been concerted efforts to improve racial and ethnic diversity in the physician-scientist workforce. Identifying factors associated with career choices among those underrepresented in medicine and science is a necessary first step to advance this objective. The aim of the present study was to assess the attitudes and factors associated with academic and research career interests among underrepresented predoctoral physician-scientists. METHODS: A cross-sectional 70-question survey was distributed to all predoctoral single degree (MD or DO) and dual degree (MD/PhD or DO/PhD) trainees at 32 medical schools in the United States from 2012 to 2014. Main outcomes included factors important to advancement in academic medicine, intended medical specialty, and future career plans. To test the post-hoc hypothesis of whether trainees from underrepresented groups have differing perceptions of career trajectories and obstacles than their counterparts, we evaluated responses according to self-identified race/ethnic status using Chi-square and Fisher's exact tests. All tests were two-sided and significance level of < 0.05 was used. RESULTS: There were a total of 4433 responses representing all predoctoral training stages. The response rate was 27%. Most respondents were single degree trainees (MD/DO 79% vs MD/DO-PhD 21%). Most respondents self-identified as White (67%), followed by Multi-racial or Other (14.3%), Asian or Pacific Islander (10.4%), Hispanic (6%), and Black or African American (4.1%). Desired career sector, career intention, and clinical specialty interest differed across race/ethnic groups. With respect to career selection factors, anticipated non-work related responsibilities during residency were also significantly different between these groups. By multivariable regression analysis, Black or African American trainees were significantly less likely than White trainees to indicate a career in academia (OR 0.496, 95% CI 0.322-0.764) and basic research (OR 0.314, 95% CI 0.115-0.857), while Multi-racial or Other trainees were also less likely than White trainees to indicate a career in academia (OR 0.763, 95% CI 0.594-0.980). CONCLUSIONS: These data represent the first in-depth survey of career aspirations, perceptions, and interests between demographically underrepresented and non-underrepresented predoctoral physician-scientist trainees. Our results identify key differences between these cohorts, which may guide efforts to improve diversity within the physician-scientist workforce.

Exploring intentions of physician-scientist trainees: factors influencing MD and MD/PhD interest in research careers.

BACKGROUND: Prior studies have described the career paths of physician-scientist candidates after graduation, but the factors that influence career choices at the candidate stage remain unclear. Additionally, previous work has focused on MD/PhDs, despite many physician-scientists being MDs. This study sought to identify career sector intentions, important factors in career selection, and experienced and predicted obstacles to career success that influence the career choices of MD candidates, MD candidates with research-intense career intentions (MD-RI), and MD/PhD candidates. METHODS: A 70-question survey was administered to students at 5 academic medical centers with Medical Scientist Training Programs (MSTPs) and Clinical and Translational Science Awards (CTSA) from the NIH. Data were analyzed using bivariate or multivariate analyses. RESULTS: More MD/PhD and MD-RI candidates anticipated or had experienced obstacles related to balancing academic and family responsibilities and to balancing clinical, research, and education responsibilities, whereas more MD candidates indicated experienced and predicted obstacles related to loan repayment. MD/PhD candidates expressed higher interest in basic and translational research compared to MD-RI candidates, who indicated more interest in clinical research. Overall, MD-RI candidates displayed a profile distinct from both MD/PhD and MD candidates. CONCLUSIONS: MD/PhD and MD-RI candidates experience obstacles that influence their intentions to pursue academic medical careers from the earliest training stage, obstacles which differ from those of their MD peers. The differences between the aspirations of and challenges facing MD, MD-RI and MD/PhD candidates present opportunities for training programs to target curricula and support services to ensure the career development of successful physician-scientists.

Akt-dependent Skp2 mRNA translation is required for exiting contact inhibition, oncogenesis, and adipogenesis.

The requirement of Akt for cell proliferation and oncogenesis is mammalian target of rapamycin complex 1 (mTORC1) dependent. SV40 large T expression in Akt-deficient cells restores cell proliferation rate, but is insufficient for exiting contact inhibition and oncogene-induced anchorage-independent growth, because of a failure to promote Skp2 mRNA translation. Skp2 mRNA and protein are induced upon exiting contact inhibition, which enables entry into mitosis. While Skp2 mRNA is induced in Akt-deficient cells, it is not translated, preventing entry into mitosis. Restoring Skp2 expression in Akt-deficient cells is sufficient to restore exit from contact inhibition and oncogenesis. Skp2 mRNA translation is dependent on mTORC1 and the eukaryotic translation initiation factor 4E (eIF4E). Thus, the requirement of Akt for exiting contact inhibition is mediated by the induction of Skp2 mRNA translation in eIF4E-dependent mechanism. These results provide a new insight into the role of the Akt/mTORC1/eIF4E axis in tumourigenesis. Akt-dependent Skp2 mRNA translation is also required for mitotic clonal expansion (MCE)--the earliest event in adipogenesis. Skp2 re-expression in Akt-deficient preadipocytes, which are impaired in adipogenesis, is sufficient to restore adipogenesis. These results uncover the mechanism by which Akt mediates adipogenesis.

T cells and lung injury. Impact of rapamycin.

Acute lung injury (ALI) is characterized by pulmonary inflammation and edema. Innate immune cells (e.g., neutrophils and macrophages) are major contributors to inflammation in ALI. Less is known regarding the role of T cells. We examined the effects of rapamycin on inflammation in a LPS-induced murine model of ALI. Rapamycin was administered before and after initiation of injury. Inflammatory parameters, including bronchoalveolar lavage cell counts, T cell surface markers (i.e., cytotoxic T lymphocyte antigen 4 [CTLA4] and fork head-winged helix transcription factor [Foxp3]), T cell activation (CD69), IL-6, and IL-10 were analyzed. Rapamycin significantly decreased inflammatory parameters and decreased Foxp3, CTLA4, and CD69 in CD4(+) T cells. Rapamycin administration before or after the onset of lung injury, as well as systemically or by pulmonary routes, ameliorates inflammation in ALI.

Clinical Biochemistry of Serum Troponin.

Accurate measurement and interpretation of serum levels of troponin (Tn) is a central part of the clinical workup of a patient presenting with chest pain suspicious for acute coronary syndrome (ACS). Knowledge of the molecular characteristics of the troponin complex and test characteristics of troponin measurement assays allows for a deeper understanding of causes of false positive and false negative test results in myocardial injury. In this review, we discuss the molecular structure and functions of the constituent proteins of the troponin complex (TnT, TnC, and TnI); review the different isoforms of Tn and where they are from; survey the evolution of clinical Tn assays, ranging from first-generation to high-sensitivity (hs); provide a primer on statistical interpretation of assay results based on different clinical settings; and discuss potential causes of false results. We also summarize the advances in technologies that may lead to the development of future Tn assays, including the development of point of care assays and wearable Tn sensors for real-time continuous measurement.

Clinical Interpretation of Serum Troponin in the Era of High-Sensitivity Testing.

Cardiac troponin (Tn) plays a central role in the evaluation of patients with angina presenting with acute coronary syndrome. The advent of high-sensitivity assays has improved the analytic sensitivity and precision of serum Tn measurement, but this advancement has come at the cost of poorer specificity. The role of clinical judgment is of heightened importance because, more so than ever, the interpretation of serum Tn elevation hinges on the careful integration of findings from electrocardiographic, echocardiographic, physical exam, interview, and other imaging and laboratory data to formulate a weighted differential diagnosis. A thorough understanding of the epidemiology, mechanisms, and prognostic implications of Tn elevations in each cardiac and non-cardiac etiology allows the clinician to better distinguish between presentations of myocardial ischemia and myocardial injury-an important discernment to make, as the treatment of acute coronary syndrome is vastly different from the workup and management of myocardial injury and should be directed at the underlying cause.

Clinical Outcomes Among Immunotherapy-Treated Patients With Primary Cardiac Soft Tissue Sarcomas: A Multicenter Retrospective Study.

Background: Primary cardiac soft tissue sarcomas (CSTS) affect young adults, with dismal outcomes. Objectives: The aim of this study was to investigate the clinical outcomes of patients with CSTS receiving immune checkpoint inhibitors (ICIs). Methods: A retrospective, multi-institutional cohort study was conducted among patients with CSTS between 2015 and 2022. The patients were treated with ICI-based regimens. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates were determined according to Response Evaluation Criteria in Solid Tumors version 1.1. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events version 5.0. Results: Among 24 patients with CSTS, 17 (70.8%) were White, and 13 (54.2%) were male. Eight patients (33.3%) had angiosarcoma. At the time of ICI treatment, 18 patients (75.0%) had metastatic CSTS, and 4 (16.7%) had locally advanced disease. ICIs were administered as the first-line therapy in 6 patients (25.0%) and as the second-line therapy or beyond in 18 patients (75.0%). For the 18 patients with available response data, objective response rate was 11.1% (n = 2 of 18). The median PFS and median OS in advanced and metastatic CSTS (n = 22) were 5.7 months (95% CI: 2.8-13.3 months) and 14.9 months (95% CI: 5.7-23.7 months), respectively. The median PFS and OS were significantly shorter in patients with cardiac angiosarcomas than in those with nonangiosarcoma CSTS: median PFS was 1.7 vs 11 months, respectively (P < 0.0001), and median OS was 3.0 vs 24.0 months, respectively (P = 0.008). Any grade treatment-related adverse events occurred exclusively in the 15 patients with nonangiosarcoma CSTS (n = 7 [46.7%]), of which 6 (40.0%) were grade ≥3. Conclusions: Although ICIs demonstrate modest activity in CSTS, durable benefit was observed in a subset of patients with nonangiosarcoma, albeit with higher toxicity.

Impact of COVID-19 Pandemic on Physician-Scientist Trainees to Faculty One Year into the Pandemic.

Purpose: Physician-scientists play a crucial role in advancing biomedical sciences. Proportionally fewer physicians are actively engaged in scientific pursuits, attributed to attrition in the training and retention pipeline. This national study evaluated the ongoing and longer-term impact of the COVID-19 pandemic on research productivity for physician-scientists at all levels of training. Methods: A survey of medical students, graduate students, and residents/fellows/junior faculty (RFJF) was conducted from April to August 2021 to assess the impact of COVID-19 on individual stress, productivity, and optimism. Multivariate regression analyses were performed to identify associated variables and unsupervised variable clustering techniques were employed to identify highly correlated responses. Results: A total 677 respondents completed the survey, representing different stages of physician-scientist training. Respondents report high levels of stress (medical students: 85%, graduate students: 63%, RFJF: 85%) attributed to impaired productivity concerns, concern about health of family and friends, impact on personal health and impairment in training or career development. Many cited impaired productivity (medical students: 65% graduate students: 79%, RFJF: 78%) associated with pandemic impacts on training, labs closures and loss of facility/resource access, and social isolation. Optimism levels were low (medical students: 37%, graduate students: 38% and RFJF: 39%) with females less likely to be optimistic and more likely to report concerns of long-term effects of COVID-19. Optimism about the future was correlated with not worrying about the long-term effects of COVID-19. Since the COVID-19 pandemic, all respondents reported increased prioritization of time with family/friends (67%) and personal health (62%) over career (25%) and research (24%). Conclusions: This national survey highlights the significant and protracted impact of the COVID-19 pandemic on stress levels, productivity, and optimism among physician-scientists and trainees. These findings underscore the urgent need for tailored support, including mental health, academic, and career development assistance for this biomedical workforce.

Quantitative cardiovascular magnetic resonance findings and clinical risk factors predict cardiovascular outcomes in breast cancer patients.

BACKGROUND: Cardiac magnetic resonance (CMR) global longitudinal strain and circumferential strain abnormalities have been associated with left ventricular ejection fraction (LVEF) reduction and cardiotoxicity from oncologic therapy. However, few studies have evaluated the associations of strain and cardiovascular outcomes. OBJECTIVES: To assess CMR circumferential and global longitudinal strain (GLS) correlations with cardiovascular outcomes including myocardial infarction, systolic dysfunction, diastolic dysfunction, arrhythmias and valvular disease in breast cancer patients treated with and without anthracyclines and/or trastuzumab therapy. METHODS: Breast cancer patients with a CMR from 2013-2017 at Yale New Haven Hospital were included. Patient co-morbidities, medications, and cardiovascular outcomes were obtained from chart review. Biostatistical analyses, including Pearson correlations, competing risk regression model, and competing risk survival curves comparing the two groups were analyzed. RESULTS: 116 breast cancer with CMRs were included in our analysis to assess differences between Anthracycline/Trastuzumab (AT) (62) treated versus non anthracycline/trastuzumab (NAT) (54) treated patients in terms of imaging characteristics and outcomes. More AT patients 17 (27.4%) developed systolic heart failure compared to the NAT group 6 (10.9%), p = 0.025. Statin use was associated with a significant reduction in future arrhythmias (HR 0.416; 95% CI 0.229-0.755, p = 0.004). In a sub-group of 13 patients that underwent stress CMR, we did not find evidence of microvascular dysfunction by sub-endocardial/sub-epicardial myocardial perfusion index ratio after adjusting for ischemic heart disease. CONCLUSIONS: In our study, CMR detected signs of subclinical cardiotoxicity such as strain abnormalities despite normal LV function and abnormal circumferential strain was associated with adverse cardiovascular outcomes such as valvular disease and systolic heart failure. Thus, CMR is an important tool during and after cancer treatment to identity and prognosticate cancer treatment-related cardiotoxicity.

Microfluidic Immuno-Serolomic Assay Reveals Systems Level Association with COVID-19 Pathology and Vaccine Protection.

How to develop highly informative serology assays to evaluate the quality of immune protection against coronavirus disease-19 (COVID-19) has been a global pursuit over the past years. Here, a microfluidic high-plex immuno-serolomic assay is developed to simultaneously measure50 plasma or serum samples for50 soluble markers including 35proteins, 11 anti-spike/receptor binding domian (RBD) IgG antibodies spanningmajor variants, and controls. This assay demonstrates the quintuplicate test in a single run with high throughput, low sample volume, high reproducibilityand accuracy. It is applied to the measurement of 1012 blood samples including in-depth analysis of sera from 127 patients and 21 healthy donors over multiple time points, either with acute COVID infection or vaccination. The protein analysis reveals distinct immune mediator modules that exhibit a reduced degree of diversity in protein-protein cooperation in patients with hematologic malignancies or receiving B cell depletion therapy. Serological analysis identifies that COVID-infected patients with hematologic malignancies display impaired anti-RBD antibody response despite high level of anti-spike IgG, which can be associated with limited clonotype diversity and functional deficiency in B cells. These findings underscore the importance to individualize immunization strategies for these high-risk patients and provide an informative tool to monitor their responses at the systems level.

Myocardial Injury on CMR in Patients With COVID-19 and Suspected Cardiac Involvement.

BACKGROUND: Myocardial injury in patients with COVID-19 and suspected cardiac involvement is not well understood. OBJECTIVES: The purpose of this study was to characterize myocardial injury in a multicenter cohort of patients with COVID-19 and suspected cardiac involvement referred for cardiac magnetic resonance (CMR). METHODS: This retrospective study consisted of 1,047 patients from 18 international sites with polymerase chain reaction-confirmed COVID-19 infection who underwent CMR. Myocardial injury was characterized as acute myocarditis, nonacute/nonischemic, acute ischemic, and nonacute/ischemic patterns on CMR. RESULTS: In this cohort, 20.9% of patients had nonischemic injury patterns (acute myocarditis: 7.9%; nonacute/nonischemic: 13.0%), and 6.7% of patients had ischemic injury patterns (acute ischemic: 1.9%; nonacute/ischemic: 4.8%). In a univariate analysis, variables associated with acute myocarditis patterns included chest discomfort (OR: 2.00; 95% CI: 1.17-3.40, P = 0.01), abnormal electrocardiogram (ECG) (OR: 1.90; 95% CI: 1.12-3.23; P = 0.02), natriuretic peptide elevation (OR: 2.99; 95% CI: 1.60-5.58; P = 0.0006), and troponin elevation (OR: 4.21; 95% CI: 2.41-7.36; P < 0.0001). Variables associated with acute ischemic patterns included chest discomfort (OR: 3.14; 95% CI: 1.04-9.49; P = 0.04), abnormal ECG (OR: 4.06; 95% CI: 1.10-14.92; P = 0.04), known coronary disease (OR: 33.30; 95% CI: 4.04-274.53; P = 0.001), hospitalization (OR: 4.98; 95% CI: 1.55-16.05; P = 0.007), natriuretic peptide elevation (OR: 4.19; 95% CI: 1.30-13.51; P = 0.02), and troponin elevation (OR: 25.27; 95% CI: 5.55-115.03; P < 0.0001). In a multivariate analysis, troponin elevation was strongly associated with acute myocarditis patterns (OR: 4.98; 95% CI: 1.76-14.05; P = 0.003). CONCLUSIONS: In this multicenter study of patients with COVID-19 with clinical suspicion for cardiac involvement referred for CMR, nonischemic and ischemic patterns were frequent when cardiac symptoms, ECG abnormalities, and cardiac biomarker elevations were present.

Radiotracers to Address Unmet Clinical Needs in Cardiovascular Imaging, Part 1: Technical Considerations and Perfusion and Neuronal Imaging.

The development of new radiotracers for PET and SPECT is central to addressing unmet diagnostic needs related to systemwide trends toward molecular characterization and personalized therapies in cardiovascular medicine. In the following 2-part review, we discuss select emerging radiotracers that may help address important unmet diagnostic needs in central areas of cardiovascular medicine, such as heart failure, arrhythmias, valvular disease, atherosclerosis, and thrombosis. Part 1 examines key technical considerations pertaining to cardiovascular radiotracer development and reviews emerging radiotracers for perfusion and neuronal imaging. Highlights of this work include discussions on the development of 18F-flurpiridaz, an emerging PET perfusion tracer, and the development of 18F-based radiotracers for cardiovascular neuronal imaging, such as 18F-flubrobenguane. Part 2 of this review covers emerging radiotracers for the imaging of inflammation, fibrosis, thrombosis, calcification, and cardiac amyloidosis.

Radiotracers to Address Unmet Clinical Needs in Cardiovascular Imaging, Part 2: Inflammation, Fibrosis, Thrombosis, Calcification, and Amyloidosis Imaging.

Cardiovascular imaging is evolving in response to systemwide trends toward molecular characterization and personalized therapies. The development of new radiotracers for PET and SPECT imaging is central to addressing the numerous unmet diagnostic needs that relate to these changes. In this 2-part review, we discuss select radiotracers that may help address key unmet clinical diagnostic needs in cardiovascular medicine. Part 1 examined key technical considerations pertaining to cardiovascular radiotracer development and reviewed emerging radiotracers for perfusion and neuronal imaging. Part 2 covers radiotracers for imaging cardiovascular inflammation, thrombosis, fibrosis, calcification, and amyloidosis. These radiotracers have the potential to address several unmet needs related to the risk stratification of atheroma, detection of thrombi, and the diagnosis, characterization, and risk stratification of cardiomyopathies. In the first section, we discuss radiotracers targeting various aspects of inflammatory responses in pathologies such as myocardial infarction, myocarditis, sarcoidosis, atherosclerosis, and vasculitis. In a subsequent section, we discuss radiotracers for the detection of systemic and device-related thrombi, such as those targeting fibrin (e.g., 64Cu-labeled fibrin-binding probe 8). We also cover emerging radiotracers for the imaging of cardiovascular fibrosis, such as those targeting fibroblast activation protein (e.g., 68Ga-fibroblast activation protein inhibitor). Lastly, we briefly review radiotracers for imaging of cardiovascular calcification (18F-NaF) and amyloidosis (e.g., 99mTc-pyrophosphate and 18F-florbetapir).

Multimodality Advanced Cardiovascular and Molecular Imaging for Early Detection and Monitoring of Cancer Therapy-Associated Cardiotoxicity and the Role of Artificial Intelligence and Big Data.

Cancer mortality has improved due to earlier detection via screening, as well as due to novel cancer therapies such as tyrosine kinase inhibitors and immune checkpoint inhibitions. However, similarly to older cancer therapies such as anthracyclines, these therapies have also been documented to cause cardiotoxic events including cardiomyopathy, myocardial infarction, myocarditis, arrhythmia, hypertension, and thrombosis. Imaging modalities such as echocardiography and magnetic resonance imaging (MRI) are critical in monitoring and evaluating for cardiotoxicity from these treatments, as well as in providing information for the assessment of function and wall motion abnormalities. MRI also allows for additional tissue characterization using T1, T2, extracellular volume (ECV), and delayed gadolinium enhancement (DGE) assessment. Furthermore, emerging technologies may be able to assist with these efforts. Nuclear imaging using targeted radiotracers, some of which are already clinically used, may have more specificity and help provide information on the mechanisms of cardiotoxicity, including in anthracycline mediated cardiomyopathy and checkpoint inhibitor myocarditis. Hyperpolarized MRI may be used to evaluate the effects of oncologic therapy on cardiac metabolism. Lastly, artificial intelligence and big data of imaging modalities may help predict and detect early signs of cardiotoxicity and response to cardioprotective medications as well as provide insights on the added value of molecular imaging and correlations with cardiovascular outcomes. In this review, the current imaging modalities used to assess for cardiotoxicity from cancer treatments are discussed, in addition to ongoing research on targeted molecular radiotracers, hyperpolarized MRI, as well as the role of artificial intelligence (AI) and big data in imaging that would help improve the detection and prognostication of cancer-treatment cardiotoxicity.

The Impact of COVID-19 on Physician-Scientist Trainees and Faculty in the United States: A National Survey.

PURPOSE: Physician-scientists have long been considered an endangered species, and their extended training pathway is vulnerable to disruptions. This study investigated the effects of COVID-19-related challenges on the personal lives, career activities, stress levels, and research productivity of physician-scientist trainees and faculty. METHOD: The authors surveyed medical students (MS), graduate students (GS), residents/fellows (R/F), and faculty (F) using a tool distributed to 120 U.S. institutions with MD-PhD programs in April-June 2020. Chi-square and Fisher's exact tests were used to compare differences between groups. Machine learning was employed to select variables for multivariate logistic regression analyses aimed at identifying factors associated with stress and impaired productivity. RESULTS: The analyses included 1,929 respondents (MS: n = 679, 35%; GS: n = 676, 35%; R/F: n = 274, 14%; F: n = 300, 16%). All cohorts reported high levels of social isolation, stress from effects of the pandemic, and negative impacts on productivity. R/F and F respondents were more likely than MS and GS respondents to report financial difficulties due to COVID-19. R/F and F respondents with a dual degree expressed more impaired productivity compared with those without a dual degree. Multivariate regression analyses identified impacted research/scholarly activities, financial difficulties, and social isolation as predictors of stress and impaired productivity for both MS and GS cohorts. For both R/F and F cohorts, impacted personal life and research productivity were associated with stress, while dual-degree status, impacted research/scholarly activities, and impacted personal life were predictors of impaired productivity. More female than male respondents reported increased demands at home. CONCLUSIONS: This national survey of physician-scientist trainees and faculty found a high incidence of stress and impaired productivity related to the COVID-19 pandemic. Understanding the challenges faced and their consequences may improve efforts to support the physician-scientist workforce in the postpandemic period.

Microfluidic immuno-serology assay revealed a limited diversity of protection against COVID-19 in patients with altered immunity.

The immune response to SARS-CoV-2 for patients with altered immunity such as hematologic malignancies and autoimmune disease may differ substantially from that in general population. These patients remain at high risk despite wide-spread adoption of vaccination. It is critical to examine the differences at the systems level between the general population and the patients with altered immunity in terms of immunologic and serological responses to COVID-19 infection and vaccination. Here, we developed a novel microfluidic chip for high-plex immuno-serological assay to simultaneously measure up to 50 plasma or serum samples for up to 50 soluble markers including 35 plasma proteins, 11 anti-spike/RBD IgG antibodies spanning all major variants, and controls. Our assay demonstrated the quintuplicate test in a single run with high throughput, low sample volume input, high reproducibility and high accuracy. It was applied to the measurement of 1,012 blood samples including in-depth analysis of sera from 127 patients and 21 healthy donors over multiple time points, either with acute COVID infection or vaccination. The protein association matrix analysis revealed distinct immune mediator protein modules that exhibited a reduced degree of diversity in protein-protein cooperation in patients with hematologic malignancies and patients with autoimmune disorders receiving B cell depletion therapy. Serological analysis identified that COVID infected patients with hematologic malignancies display impaired anti-RBD antibody response despite high level of anti-spike IgG, which could be associated with limited clonotype diversity and functional deficiency in B cells and was further confirmed by single-cell BCR and transcriptome sequencing. These findings underscore the importance to individualize immunization strategy for these high-risk patients and provide an informative tool to monitor their responses at the systems level.