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Introduction

Dear Colleagues and Friends of CIRC,

 

This month’s introduction is focused on the efforts within CIRC to better understand the cardiovascular disease associated with novel cancer therapies. 

As this group is aware, there are many factors that lead to increase in cardiovascular disease in cancer patients. Some of these factors include shared risk factors for cancer and cardiovascular disease, overlapping biological mechanisms, and in some, an adverse effect of cancer therapies. Example of the shared risk factors are highlighted by work from this group (Pursani et al, JCO, 2017), where in a community-based primary prevention cohort, guideline-based statin eligibility accurately identified patients at a higher risk of developing cancer and cancer-related mortality. Paralleling these efforts to better understand the cross-section of risk factors for cancer and cardiovascular disease is a focus on adverse cardiac events related to cancer therapies. Several established cancer therapies have been linked to an increase in cardiovascular events. In July, this group completed enrollment for STOP-CA. STOP-CA is funded by the National Heart, Lung, and Blood Institute (R01HL130539) and is an investigator-initiated double-blind placebo controlled clinical trial testing whether statin therapy is associated with preservation of cardiac function (LV EF by cardiac MRI) among patients with lymphoma. Other endpoints include cardiac fibrosis by MRI, global longitudinal strain by echocardiography and serum biomarkers. 

The treatment of patients with cancer has evolved and continues to evolve. Immune checkpoint inhibitors (ICI’s) represent a paradigm shift in the care of patients with cancer. They leverage the remarkable power of the immune system to target and kill cancer cells (Figure, Zhang, Neilan, JACC CO, 2020). In brief, cancer cells escape immune recognition by triggering the overexpression or activation of inhibitor checkpoint pathways. These pathways include those that block programmed death receptor 1 (PD-1), programmed death receptor 1 ligand (PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Immune checkpoint inhibitors are monoclonal antibodies (e.g., anti-PD-1, anti-PD-L1 and anti-CTLA-4) that block this process, thus activating T cells and initiating an adaptive immune response, allowing the immune system to recognize abnormal cancerous cells. However, work from CIRC and others has highlighted how ICIs are also associated with both acute and chronic adverse effects on the cardiovascular system. Acutely, these ICIs are associated with an acute and fulminant myocarditis (Mahmood, JACC, 2018) , an increase in arrythmias (D’Souza, EHJ, 2021), and pericardial disease (Gong, JITC, 2021). Sub-acutely, a collaboration within CIRC, showed that these ICIs are associated with a 3-fold increase in progression of atherosclerosis (Drobni, Circulation, 2020) using CT and parallel 3-fold increase in atherosclerotic-related cardiovascular events (Drobni, Circulation, 2020). 
These insights on the effect of ICIs on the cardiovascular system have led to many scientific questions. We hope that you will continue to join us at CIRC as we strive to address some of these. 

Sincerely,
Tom
 
Tomas Neilan, MD, MPH

Co-Director of the MGH Cardiovascular Imaging Research Center (CIRC)

Director, Cardio-Oncology Program, MGH
Research Highlights
Dr. Shady Abohashem and Dr. Azar Radfar

"Stress-associated neurobiological activity associates with the risk for and timing of subsequent Takotsubo syndrome " European Heart Journal 2021

Our Study reveals that a stressed brain is linked to " Broken Heart " Syndrome (aka-Takotsubo Syndrome {TTS}), a rare (was first described in 1990) and stress-driven heart condition that is usually the result of severe emotional or physical stress, such as a sudden illness, a breakup, the loss of a loved one or a serious accident. 
 
The name 'Takotsubo syndrome' comes from the shape the heart takes during an episode of heartbreak. The left pumping chamber of the heart stretches outward like a balloon, while the base of the muscle inverts, pulling inward. The combined effect renders the heart too weak to pump blood properly. And, according to the Japanese scientists that first discovered the phenomenon, the contorted heart resembles a 'Takotsubo' - an octopus-catching pot.
 
Broken heart syndrome's exact cause and mechanisms aren't clear – but this study shows stress-related activity in the amygdala could be a cause. The amygdala is an almond-shaped structure in the brain that controls emotions, motivation, learning and memory - and are essential to the ability to feel certain emotions and to perceive them in other people. TTS is more common in women, with only 10 per cent of cases occurring in men.
 
Accordingly, we leveraged 18F-FDG-PET/CT imaging in a retrospective cohort of individuals who underwent clinically indicated imaging prior to TTS onset to test our hypotheses that (i) individuals who develop TTS have heightened AmygA prior to TTS onset, and (ii) among those with subsequent TTS, higher AmygA associates with a shorter duration between imaging and TTS. We discovered that people who went on to develop TTS had higher 'stress-related amygdalar activity' on initial scanning compared to individuals who did not subsequently develop TTS. This heightened stress-associated neurobiological activity is present years before disease onset and may represent a previously unrecognized TTS risk factor. It was notable that among the patients who developed TTS, the top 15 per cent with the very highest amygdalar activity developed TTS within a year of imaging, while those with less elevated activity developed TTS several years later. Collectively, these findings shed light on a ‘heart–brain connection’ representing a neurobiological mechanism that contributes to TTS and suggests potential targets to reduce TTS risk.
 
Dr. Jingyi Gong

"Pericardial disease in patients treated with immune checkpoint inhibitors" Journal for ImmunoTherapy of Cancer 2021

This is was a retrospective study leveraging the Mass General Brigham cancer patients who received immune checkpoint inhibitors (ICIs). We included 2842 patients who received ICIs for cancer treatment and 2699 age- and cancer-type matched patients with metastatic disease who did not receive ICI.  We reviewed rates of pericardial events (defined as pericarditis and new or worsening moderate or large pericardial effusion) between the two groups and found that there was a more than fourfold increase in risk for pericarditis or a pericardial effusion among patients on an ICI compared with controls not treated with ICI, after adjusting for potential confounders (HR 4.37, 95% CI 2.09 to 9.14, p<0.001). The median time of onset of pericardial disease was approximately 6 months. Patients who developed pericardial disease while on an ICI had a trend for increased all-cause mortality compared with patients who did not develop a pericardial event (HR 1.53, 95% CI 0.99 to 2.36, p=0.05). The study further evaluated risk factors associated with development of pericardial disease in patients treated with ICIs by comparing patients who developed an event on an ICI with patients treated with an ICI who did not develop a pericardial event. We observed that a higher dose of corticosteroid pre-ICI (>0.7 mg/kg prednisone) was associated with increased risk of pericardial disease (HR 2.56, 95% CI 1.00 to 6.57, p=0.049).  This was the first large cohort study that outlined the risk of pericardial disease in patients treated with ICI in comparison to a control group. Our findings further highlight that pericardial disease is an under-recognized toxicity with ICI use.

Link to paper: https://pubmed.ncbi.nlm.nih.gov/34145031/
Dr. Kenechukwu Mezue

"Alcohol's beneficial effect on cardiovascular disease is partially mediated through modulation of stress-associated brain activity" JACC 2021

Our study aimed to find out if moderate alcohol intake's protective effect on cardiovascular disease could be due to its effects on reducing stress-associated neural activity. Of the 50,559 participants, 6,648 (13.1%) experienced a major adverse cardiovascular event: 15% in the low alcohol intake group and 11% in the moderate alcohol intake group. People who reported moderate alcohol intake were found to have a 13% lower chance of having a major event compared to low alcohol intake. This remained significant even after controlling for demographic variables, cardiovascular risk factors, socioeconomic variables, and psychological factors. We also found that stress-related activity in the brain was higher in non-drinkers when compared with people who drank moderately. Path analyses (mediation analysis) showed that the link between moderate alcohol intake and lowered cardiovascular event risk is significantly mediated through reductions in stress-associated neural activity. Our study suggests that moderate alcohol intake beneficially impacts the brain-heart connection. However, alcohol has several important side effects, including an increased risk of cancer, liver damage, and dependence, so other interventions with better side effect profiles that beneficially impact brain-heart pathways are needed.

Link to abstract: https://www.jacc.org/doi/10.1016/S0735-1097%2821%2901349-8
Dr. Hadil Zureigat

"Exercise lowers stress-associated neurobiological activity: potential mechanism contributing to cardiovascular risk reduction" JACC 2021

Our findings suggest that brain mechanisms may be in-part responsible for exercise’s beneficial effects on cardiovascular disease (CVD) risk. We observed a dose-dependent association between increased exercise and reduced stress-related neurobiological activity. Further, the reductions in stress-related activity related to increased exercise were primarily achieved by enhancing the activity of the medial prefrontal cortex (a cortical area that attenuates  the stress response). Additionally, we observed that exercise associates with greater CVD reductions among the subset of individuals with stress-related conditions (such as anxiety and depression), compared to the general population. These findings thus highlight the importance of stress-related pathways in mediating some of the beneficial impacts of exercise on CVD risk.

Link to abstract: https://www.jacc.org/doi/10.1016/S0735-1097%2821%2901358-9
Awards and Honors
Shady Abohashem, MD, M.B.,B.Ch., clinical research fellow in the Cardiology Division, has been selected to participate in the American Society of Nuclear Cardiology's (ASNC) 2021-2022 Leadership Development Program (LDP). Selection to the program was based on demonstrated dedication to nuclear cardiology; participation in ASNC and other imaging society activities; and research, advocacy and leadership potential. As LDP participants, they willl participate in a series of activities designed to help them grow as leaders both in ASNC and the specialty of cardiovascular imaging.
Marton Kolossvary, PhD, MD was awarded an Ralph Schlaeger Charitable Foundation Research Fellow Grant.
Title: Deep Learning Analysis of Chest X-rays to Expedite Safe Discharge of Patients Presenting to the Emergency Department with Acute Chest Pain
Description: In the United States alone, over 7 million patients are evaluated for acute chest pain annually, constituting 5.5% of all ED visits. In the majority of cases, patients are discharged from the hospitals after several costly imaging exams. With the support of the Ralph Schlaeger grant, we wish to develop a deep learning model using chest X-rays to help identify patients who may be safely discharged from the ED without the use of additional imaging studies.
Michael Osborne, MD was awarded an NIH K23 Career Development Award from the NHLBI to further his study of the neuro-immune mechanisms linking chronic stress to cardiovascular disease. He will implement multi-system 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging to study the impact of a stress reduction intervention on brain activity, inflammation, and atherosclerosis in individuals with stable coronary artery disease in a randomized controlled trial under the mentorship of Dr. Ahmed Tawakol. The study will run through January 2026. In addition, in the past year, Dr. Osborne was named the Associate Director of Nuclear Cardiology: Education at MGH, was named an Associate Editor for the Journal of Translational Medicine, was appointed to the American Society of Nuclear Cardiology Leadership Development Program and PET Committee, and was nominated for the Harvard Medical School Excellence in Mentoring Award and Brian A. McGovern Memorial Clinical Teaching Award by MGH Internal Medicine residents.
Pedro V. Staziaki, MD was awarded an Ralph Schlaeger Charitable Foundation Research Fellow Grant.
Title: Development of a machine learning model for prediction of cardiovascular imaging CT exam protocol with prospective validation
Description: This project will develop a machine learning model that utilizes easily accessible information to suggest to the cardiovascular resident/fellow the most likely protocol for a CT order. The main objective is for the model to become an automated protocol predictor, bringing the most likely protocol to the trainee’s attention.
CIRC at Upcoming Conferences
Promotions
Shady Abohashem has been promoted to a faculty position of Instructor at CIRC and Harvard Medical School. Shady is focused on studying a Neuro-Immuno-Arterial biological axis, via employing Advanced non-invasive multimodality molecular imaging approaches (i.e., PET/CT, MRI), to understand the underlying link between socio-environmental stressors and cardiovascular disease risk in different populations including those with RA and HIV. His current projects aim to investigate the interaction between genetic risk, environmental pathogens, lifestyle factors, imaging indices and their contributions to aortic valve disease risk and other cardiovascular disorders.
Vinit Baliyan has been promoted to assistant professor. He is a radiologist with subspeciality expertise in Cardiovascular imaging and Emergency radiology. Vinit's research is focused on advancing the use of novel CT and MRI technology in the imaging of heart, abdomen, and blood vessels. A large part of this research is focused on advancing the use of Dual energy CT (DECT) technology. His research in cardiac domain is focused on bringing new insights in the understanding cardiovascular disease processes, improving implementation of CT technology in heart disease, and highlighting the preventive opportunities offered by coronary CTA. 
Vineet K. Raghu has been promoted to research faculty and an Instructor of Radiology at CIRC. He earned a PhD degree in computer science from the University of Pittsburgh prior to joining CIRC as a T32 fellow in July 2019. Vineet will continue to develop the machine learning group at CIRC, whose main focus is to develop computational tools to estimate chronic disease risk and aging from routine medical imaging. 
Hannah Gilman has been promoted to Project Manager. She manages the STOP-CA trial with Dr. Tomas Neilan.
Welcome New Members!
 
Dr. Wesam Aldosoky joins CIRC to work with Dr. Ahmed Tawakol. Dr. Aldosoky comes from Mansoura, Egypt where she earned her MD. Her research aims to investigate the Brain-Immuno-Heart axis via leveraging advanced multimodality imaging techniques and MGB biobank to understand the pathological drivers and underlying mechanisms of cardiovascular diseases among different populations including ones with chronic inflammatory conditions. Additionally, she will be studying the impact of lifestyle modifications and socio-environmental factors and their interplay with imaging and genetic biomarkers on CVD risk.
Kanako Ando joins us as a Clinical Research Coordinator I. She works on the GOLDILOX-MEDI6570-TIMI69 trial with AstraZeneca as well as the UGANDA project with Dr. Mark Siedner. She also handles IRBs for CIRC.
Radhika Barve joins as a Clinical Research Coordinator I. Radhika works on the REPRIEVE trial, EPIC HIV and Sandeeps project.
Dr. Kenechukwu Mezue joins us as a Research Fellow. Kene is interested in the complex relationships of various demographic, social, behavioral, environmental, and genetic risk factors that predispose individuals to cardiovascular disease and venous thromboembolism. His research utilizes clinical data from the Mass General Brigham Biobank and EKG/multimodality imaging data from the Mass General Brigham health system to define these relationships and proposes novel mechanistic insights into the pathways that are both protective and deleterious to cardiovascular health.
Trinity Nguyen is joining CIRC as a Grants Coordinator. She will also handle HR and administrative issues for the team. Trinity has a BS in Pharmaceutical Sciences from the Massachusetts College of Pharmacy and Health Sciences. She is currently working on getting her MBA with a focus in Healthcare Management.
Sophia Nikolaidou joins us as a Clinical Research Coordinator I. Sophia is coordinating Dr. Tomas Nelian's STOP-CA project.
Supraja Sama joins us as a Clinical Research Coordinator I. Supraja is coordinating Dr. Tomas Neilan’s STOP-CA project.
Audra Sturniolo is joining CIRC as a Clinical Research Coordinator II. She will be assisting with IT tasks and learning more about the ongoing research studies at CIRC. Audra has a BA in Psychology from Rollins College and is currently a student at Sacred Heart University in the Healthcare Informatics graduate program. 
Audra has five years of clinical experience working at AdventHealth and Orlando Health and also has experience working in psychiatry. She is excited to learn more about working in clinical research and data analytics, and studies programming on her own time. Outside of work, Audra enjoys trail running and video games.
 
Dr. Angelo Takigami joins us as a Research Fellow. Angelo will be working on the epidemiology of cardiovascular disease among people with HIV in Uganda with Dr. Mark Siedner.
Farewell
Zsofia Drobni has returned to Semmelweis University, where she has started cardiology training. She is working on establishing a university wide cardio-oncology program.
Sarah Hartmann was a Clinical Research Coordinator working with Dr. Tomas Neilan's group. She has recently started medical school at the University of Connecticut. 
Rochelle Louis primarily worked on three clinical trials, REPRIVE, EPIC-HIV and GOLDILOX, that employ serial CCTAs to evaluate the progression of non-calcified coronary atherosclerotic plaque (NCP) and inflammatory biomarkers. She also worked on the PREPARE sub-study to measure muscle density in people living with HIV. Rochelle is now pursuing her Master of Business Administration with a specialization in Health Sector Management at the Rotman School of Management at the University of Toronto. She is working towards a career in the healthcare industry, with the long-term goal of tackle challenging problems like the lack of diversity in clinical trials and the barriers to accessing drugs and vaccines.
Vikas Thondapu recently left CIRC to begin diagnostic radiology residency at Yale New Haven Hospital and School of Medicine. After completing medical training, he undertook at PhD in biomedical engineering, focused on the combination of intracoronary optical coherence tomography and computational fluid dynamics. He then completed post-doctoral research fellowships in the Cardiac Laboratory for Integrative Physiology and Imaging and then at CIRC, where he focused on coronary computed tomography in Ugandan patients with HIV.
Namrata Upadhyay was a Clinical Research Coordinator working on the UGANDA CAD trial. Namrata is starting a 3 year direct-entry nurse practitioner program at Yale University. She'll be in the acute care specialty. Upon graduation, she is hoping to work as a NP in a cardiac ICU setting.
New Publications

Bloom, J. P., Attia, R. Q., Sundt, T. M., Cameron, D. E., Hedgire, S. S., Bhatt, A. B., Isselbacher, E. M., Srivastava, S. D., Kwolek, C. J., Eagleton, M. J., Mohebali, J., & Jassar, A. S. (2021). Outcomes of open and endovascular repair of Kommerell diverticulum. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, 60(2), 305–311. https://doi.org/10.1093/ejcts/ezab072

Foldyna, B., Zeleznik, R., Eslami, P., Mayrhofer, T., Scholtz, J. E., Ferencik, M., Bittner, D. O., Meyersohn, N. M., Puchner, S. B., Emami, H., Pellikka, P. A., Aerts, H., Douglas, P. S., Lu, M. T., & Hoffmann, U. (2021). Small whole heart volume predicts cardiovascular events in patients with stable chest pain: Insights from the PROMISE trial. European radiology, 31(8), 6200–6210. https://doi.org/10.1007/s00330-021-07695-2

de Souza, T. F., Silva, T. Q., Antunes-Correa, L., Drobni, Z. D., Costa, F. O., Dertkigil, S., Nadruz, W., Brenelli, F., Sposito, A. C., Matos-Souza, J. R., Jr, Coelho, O. R., Neilan, T. G., Jerosch-Herold, M., & Coelho-Filho, O. R. (2021). Cardiac magnetic resonance assessment of right ventricular remodeling after anthracycline therapy. Scientific reports, 11(1), 17132. https://doi.org/10.1038/s41598-021-96630-y

Guidon, A. C., Burton, L. B., Chwalisz, B. K., Hillis, J., Schaller, T. H., Amato, A. A., Betof Warner, A., Brastianos, P. K., Cho, T. A., Clardy, S. L., Cohen, J. V., Dietrich, J., Dougan, M., Doughty, C. T., Dubey, D., Gelfand, J. M., Guptill, J. T., Johnson, D. B., Juel, V. C., Kadish, R., … Reynolds, K. L. (2021). Consensus disease definitions for neurologic immune-related adverse events of immune checkpoint inhibitors. Journal for immunotherapy of cancer, 9(7), e002890. https://doi.org/10.1136/jitc-2021-002890

Hoffmann U, Lu MT, Foldyna B, Zanni MV, Karady J, Taron J, Zhai BK, Burdo T, Fitch KV, Kileel EM, Williams K, Fichtenbaum CJ, Overton ET, Malvestutto C, Aberg J, Currier J, Sponseller CA, Melbourne K, Floris-Moore M, Van Dam C, Keefer MC, Koletar SL, Douglas PS, Ribaudo H, Mayrhofer T, Grinspoon SK; REPRIEVE trial. Assessment of Coronary Artery Disease With Computed Tomography Angiography and Inflammatory and Immune Activation Biomarkers Among Adults With HIV Eligible for Primary Cardiovascular Prevention. JAMA Netw Open. 2021 Jun 1;4(6):e2114923. https://doi.org/10.1001/jamanetworkopen.2021.14923

Lopez, D. M., Divakaran, S., Gupta, A., Bajaj, N. S., Osborne, M. T., Zhou, W., Hainer, J., Bibbo, C. F., Skali, H., Dorbala, S., Taqueti, V. R., Blankstein, R., & Di Carli, M. F. (2021). Role of Exercise Treadmill Testing in the Assessment of Coronary Microvascular Disease. JACC. Cardiovascular imaging, S1936-878X(21)00567-2. Advance online publication. https://doi.org/10.1016/j.jcmg.2021.07.013

Meyersohn, N. M., Mayrhofer, T., Corey, K. E., Bittner, D. O., Staziaki, P. V., Szilveszter, B., Hallett, T., Lu, M. T., Puchner, S. B., Simon, T. G., Foldyna, B., Voora, D., Ginsburg, G. S., Douglas, P. S., Hoffmann, U., & Ferencik, M. (2021). Association of hepatic steatosis with major adverse cardiovascular events, independent of coronary artery disease. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association, 19(7), 1480–1488.e14. https://doi.org/10.1016/j.cgh.2020.07.030

Osborn, E. A., Ughi, G. J., Verjans, J. W., Piao, Z., Gerbaud, E., Albaghdadi, M., Khraishah, H., Kassab, M. B., Takx, R., Cui, J., Mauskapf, A., Shen, C., Yeh, R. W., Klimas, M. T., Tawakol, A., Tearney, G. J., & Jaffer, F. A. (2021). Intravascular Molecular-Structural Assessment of Arterial Inflammation in Preclinical Atherosclerosis Progression. JACC. Cardiovascular imaging, S1936-878X(21)00507-6. Advance online publication. https://doi.org/10.1016/j.jcmg.2021.06.017

Osborne, M. T., Naddaf, N., Abohashem, S., Radfar, A., Ghoneem, A., Dar, T., Wang, Y., Patrich, T., Oberfeld, B., Tung, B., Pitman, R. K., Mehta, N. N., Shin, L. M., Lo, J., Rajagopalan, S., Koenen, K. C., Grinspoon, S. K., Fayad, Z. A., & Tawakol, A. (2021). A neurobiological link between transportation noise exposure and metabolic disease in humans. Psychoneuroendocrinology, 131, 105331. https://doi.org/10.1016/j.psyneuen.2021.105331

Raghu, V. K., & Lu, M. T. (2021). Can deep learning classify stroke subtypes from chest X-rays?. EBioMedicine, 70, 103517. https://doi.org/10.1016/j.ebiom.2021.103517
Radfar, A., Abohashem, S., Osborne, M.T., Wang, Y., Dar, T., Hassan, M.Z.O., Ghoneem, A., Naddaf, N., Patrich, T., Abbasi, T., Zureigat, H., Jaffer, J., Ghazi, P., Scott, J.A., Shin, L.M., Pitman, R.K., Neilan, T.G., Wood, M.J., Tawakol, A. (2021). Stress-associated neurobiological activity associates with the risk for and timing of subsequent Takotsubo syndrome. European Heart Journal, 42(19), 1898-1908. https://doi.org/10.1093/eurheartj/ehab029
Strohbehn, I. A., Street, S., Chute, D., Seeethapathy, H., Lee, M., Seethapathy, R., Drobni, Z. D., Rahma, O., Neilan, T. G., Zubiri, L., Reynolds, K., & Sise, M. E. (2021). Immune checkpoint inhibitor-induced thyroiditis is a risk factor for acute and chronic kidney dysfunction. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, gfab240. Advance online publication. https://doi.org/10.1093/ndt/gfab240
Takigami AK, Thondapu V, Goiffon RJ, Depetris J, Gupta S, Garrana S, Knyazev V, Tower-Rader A, Lu MT, Meyersohn N, Hoffmann U, Hedgire S, Ghoshhajra B. Coronary Artery Disease Reporting and Data System (CAD-RADS) Adoption: Analysis of Local Trends in a Large Academic Medical Center. Radiol Cardiothorac Imaging. 2021 Jun 24;3(3):e210016. https://doi.org/10.1148/ryct.2021210016
Tehrani, D. M., Wang, X., Rafique, A. M., Hayek, S. S., Herrmann, J., Neilan, T. G., Desai, P., Morgans, A., Lopez-Mattei, J., Parikh, R. V., & Yang, E. H. (2021). Impact of cancer and cardiovascular disease on in-hospital outcomes of COVID-19 patients: results from the american heart association COVID-19 cardiovascular disease registry. Cardio-oncology (London, England), 7(1), 28. https://doi.org/10.1186/s40959-021-00113-y

Thondapu, V., Montes, D., Rosovsky, R., Dua, A., McDermott, S., Lu, M. T., Ghoshhajra, B., Hoffmann, U., Gerhard-Herman, M. D., & Hedgire, S. (2021). Venous thrombosis, thromboembolism, biomarkers of inflammation, and coagulation in coronavirus disease 2019. Journal of vascular surgery. Venous and lymphatic disorders, 9(4), 835–844.e4. https://doi.org/10.1016/j.jvsv.2020.11.006

Weiss J, Taron J, Jin Z, Mayrhofer T, Aerts HJWL, Lu MT, Hoffmann U. Radiologists can visually predict mortality risk based on the gestalt of chest radiographs comparable to a deep learning network. Sci Rep. 2021 Oct 1;11(1):19586. https://doi.org/10.1038/s41598-021-99107-0

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