Research Spotlight

Posted September 20th 2020

Integrated Genomic Characterization of the Human Immunome in Cancer.

Erxi Wu, Ph.D.

Erxi Wu, Ph.D.

Li, Y., Burgman, B., McGrail, D.J., Sun, M., Qi, D., Shukla, S.A., Wu, E., Capasso, A., Lin, S.Y., Wu, C.J., Eckhardt, S.G., Mills, G.B., Li, B., Sahni, N. and Yi, S.S. (2020). “Integrated Genomic Characterization of the Human Immunome in Cancer.” Cancer Res Aug 27;canres.0384.2020. [Epub ahead of print.].

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Alterations in immune-related pathways are common hallmarks of cancer. A comprehensive understanding of how cancer mutations rewire immune signaling networks and functional output across cancer types is instrumental to realize the full potential of immunotherapy. Here we systematically interrogated somatic mutations involved in immune signaling that alter immune responses in cancer patients. To do so, we developed a Network-based Integrative model to Prioritize Potential immune respondER genes (NIPPER). Identified mutations were enriched in essential protein domains and genes identified by NIPPER were associated with responsiveness to multiple immunotherapy modalities. These genes were used to devise an interactome network propagation framework integrated with drug-associated gene signatures to identify potential immunomodulatory drug candidates. Together, our systems-level analysis results help interpret the heterogeneous immune responses among patients and serve as a resource for future functional studies and targeted therapeutics.


Posted September 20th 2020

Ethical decision-making in simultaneous heart-liver transplantation.

Anji Wall, M.D.

Anji Wall, M.D.

Cheng, X.S., Wall, A. and Teuteberg, J. (2020). “Ethical decision-making in simultaneous heart-liver transplantation.” Curr Opin Organ Transplant Aug 31. [Epub ahead of print.].

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PURPOSE OF REVIEW: Simultaneous heart-liver (SHL) transplants are only a small proportion of overall heart and liver transplantation, they have been increasing in frequency and thus challenge the equitable allocation of organs. RECENT FINDINGS: The incidence of SHL transplants is reviewed along with the outcomes of SHL transplants and their impact on the waitlist, particularly in the context of solitary heart and liver transplantation. The ethical implications, most importantly the principles of utility and equity, of SHL transplant are addressed. In the context of utility, the distinction of a transplant being life-saving versus life-enhancing is investigated. The risk of hepatic decompensation for those awaiting both solitary and combined organ transplantation is an important consideration for the principle of equity. Lastly, the lack of standardization of programmatic approaches to SHL transplant candidates, the national approach to allocation, and the criteria by which programs are evaluated are reviewed. SUMMARY: As with all multiorgan transplantation, SHL transplantation raises ethical issues of utility and equity. Given the unique patient population, good outcomes, lack of alternatives, and overall small numbers, we feel there is continued ethical justification for SHL, but a more standardized nationwide approach to the evaluation, listing, and allocation of organs is warranted.


Posted September 20th 2020

Hot topics in interventional cardiology: Proceedings from the society for cardiovascular angiography and interventions 2020 think tank.

Molly Szerlip M.D.

Molly Szerlip M.D.

Naidu, S.S., Coylewright, M., Hawkins, B.M., Meraj, P., Morray, B.H., Devireddy, C., Ing, F., Klein, A.J., Seto, A.H., Grines, C.L., Henry, T.D., Rao, S.V., Duffy, P.L., Amin, Z., Aronow, H.D., Box, L.C., Caputo, R.P., Cigarroa, J.E., Cox, D.A., Daniels, M.J., Elmariah, S., Fagan, T.E., Feldman, D.N., Forbes, T.J., Hermiller, J.B., Herrmann, H.C., Hijazi, Z.M., Jeremias, A., Kavinsky, C.J., Latif, F., Parikh, S.A., Reilly, J., Rosenfield, K., Swaminathan, R.V., Szerlip, M., Yakubov, S.J., Zahn, E.M., Mahmud, E., Bhavsar, S.S., Blumenthal, T., Boutin, E., Camp, C.A., Cromer, A.E., Dineen, D., Dunham, D., Emanuele, S., Ferguson, R., Govender, D., Haaf, J., Hite, D., Hughes, T., Laschinger, J., Leigh, S.M., Lombardi, L., McCoy, P., McLean, F., Meikle, J., Nicolosi, M., O’Brien, J., Palmer, R.J., Patarca, R., Pierce, V., Polk, B., Prince, B., Rangwala, N., Roman, D., Ryder, K., Tolve, M.H., Vang, E., Venditto, J., Verderber, P., Watson, N., White, S. and Williams, D.M. (2020). “Hot topics in interventional cardiology: Proceedings from the society for cardiovascular angiography and interventions 2020 think tank.” Catheter Cardiovasc Interv Aug 25. [Epub ahead of print.].

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The society for cardiovascular angiography and interventions (SCAI) think tank is a collaborative venture that brings together interventional cardiologists, administrative partners, and select members of the cardiovascular industry community for high-level field-wide discussions. The 2020 think tank was organized into four parallel sessions reflective of the field of interventional cardiology: (a) coronary intervention, (b) endovascular medicine, (c) structural heart disease, and (d) congenital heart disease (CHD). Each session was moderated by a senior content expert and co-moderated by a member of SCAI’s emerging leader mentorship program. This document presents the proceedings to the wider cardiovascular community in order to enhance participation in this discussion, create additional dialogue from a broader base, and thereby aid SCAI and the industry community in developing specific action items to move these areas forward.


Posted September 20th 2020

Impact of the COVID-19 pandemic on interventional cardiology training in the United States.

Molly Szerlip M.D.

Molly Szerlip M.D.

Shah, S., Castro-Dominguez, Y., Gupta, T., Attaran, R., Byrum, G.V., 3rd, Taleb, A., Pettyjohn, A., Bartel, R.C., Szerlip, M., Henry, T.D., Mahmud, E. and Applegate, R.J. (2020). “Impact of the COVID-19 pandemic on interventional cardiology training in the United States.” Catheter Cardiovasc Interv Aug 7;10.1002/ccd.29198. [Epub ahead of print.].

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OBJECTIVES: We sought to determine the effect of COVID-19 related reduction in elective cardiac procedures and acute coronary syndrome presentations on interventional cardiology (IC) training. BACKGROUND: The COVID-19 pandemic has significantly disrupted healthcare in the United States, including cardiovascular services. The impact of COVID-19 on IC fellow training in the United States has not been assessed. METHODS: The Society for Cardiovascular Angiography and Interventions (SCAI) surveyed IC fellows training in both accredited and advanced non-accredited programs, as well as their program directors (PD). RESULTS: Responses were received from 135 IC fellows and 152 PD. All respondents noted reductions in procedural volumes beginning in March 2020. At that time, only 43% of IC fellows had performed >250 PCI. If restrictions were lifted by May 15, 2020 78% of IC fellows believed they would perform >250 PCI, but fell to only 70% if restrictions persisted until the end of the academic year. 49% of IC fellows felt that their procedural competency was impaired by COVID-19, while 97% of PD believed that IC fellows would be procedurally competent at the end of their training. Most IC fellows (65%) noted increased stress at work and at home, and many felt that job searches and/or existing offers were adversely affected by the pandemic. CONCLUSION: The COVID-19 pandemic has substantially affected IC training in the United States, with many fellows at risk of not satisfying current program procedural requirements. These observations support a move to review current IC program requirements and develop mitigation strategies to supplement gaps in education related to reduced procedural volume.


Posted September 20th 2020

The utilization of an overground robotic exoskeleton for gait training during inpatient rehabilitation-single-center retrospective findings.

Chad Swank, Ph.D.

Chad Swank, Ph.D.

Swank, C., Trammell, M., Bennett, M., Ochoa, C., Callender, L., Sikka, S. and Driver, S. (2020). “The utilization of an overground robotic exoskeleton for gait training during inpatient rehabilitation-single-center retrospective findings.” Int J Rehabil Res 43(3): 206-213.

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Overground robotic exoskeleton gait training is increasingly utilized during inpatient rehabilitation yet without clear guidelines. We describe clinical characteristics associated with robotic exoskeleton gait training and examine outcomes of people with spinal cord injury and stroke who completed usual rehabilitation care with or without robotic exoskeleton gait training. Retrospective review of medical records over a 36 months period. Inpatients with spinal cord injury or stroke and ≥1 robotic exoskeleton gait training session were included. After obtaining a complete list of robotic exoskeleton gait training participants, medical records were reviewed for comparable matches as determined by gait functional independence measure score <4, age 18-100 years, meeting exoskeleton manufacturer eligibility criteria, and participating in usual care only. Functional independence measure was collected on all patients. For spinal cord injury, we collected the walking index for spinal cord injury II. For stroke, we collected the Stroke Rehabilitation Assessment of Movement Measure. Fifty-nine people with spinal cord injury (n = 31 robotic exoskeleton gait training; n = 28 usual care) and 96 people post-stroke (n = 44 robotic exoskeleton gait training; n = 52 usual care) comprised the medical record review. Fifty-eight percent of patients with spinal cord injury and 56% of patients post-stroke completed 5+ robotic exoskeleton gait training sessions and were included in analyses. Robotic exoskeleton gait training dosage varied between our patients with spinal cord injury and patients post-stroke. Robotic exoskeleton gait training utilization during inpatient rehabilitation required consideration of unique patient characteristics impacting functional outcomes. Application of robotic exoskeleton gait training across diagnoses may require different approaches during inpatient rehabilitation.