Thomas Both

All Publications

• Recurrent Status Epilepticus in the Setting of Chimeric Antigen Receptor (CAR)-T Cell Therapy The Neurohospitalist Reveron-Thornton, R., Scott, B. J., Post, D., Finley Caulfield, A., Werbaneth, K., Hovsepian, D. A., Spiegel, J., Miklos, D., Thomas, R. P., Patel, C. B. 2021: 74-79

  Abstract

  Axicabtagene ciloleucel (AC) is an FDA-approved anti-CD19 autologous chimeric antigen receptor T-cell (CAR-T) therapy for refractory diffuse large B cell lymphoma (DLBCL). While its efficacy in DLBCL has been promising, neurotoxicity remains a significant concern. We present a case of a 22-year-old woman with chemotherapy-refractory DLBCL who exhibited Grade IV neurotoxicity in the setting of sepsis, after undergoing AC infusion. Despite prophylactic levetiracetam given per guidelines,1,2 she experienced a precipitous mental status decline on post-infusion day 8 (D8) followed by hypoxic respiratory failure in the setting of clinical status epilepticus on D11 and nonconvulsive status epilepticus (NCSE) on D18. While neuroimaging was unremarkable, EEG demonstrated diffuse slowing and 2.5-3 Hz generalized periodic discharges consistent with NCSE. Seizures were initially refractory to lorazepam, increasing doses of levetiracetam, and phenobarbital, requiring a midazolam drip titrated to 50-70% burst suppression for resolution. Methylprednisolone and tocilizumab were used to treat neurotoxicity and cytokine release syndrome, respectively. Empiric antibiotics were used for sepsis. After cessation of sedatives on D19, mental status improved to near baseline. PET/CT just prior to discharge showed a complete response of the DLBCL (Deauville 3). She was discharged on D37 with no further seizure activity. Unfortunately, a 3-month interval PET/CT demonstrated disease progression which continued through salvage pembrolizumab eventually leading to death 1.2 years post-CAR-T infusion. This case illustrates the clinical management challenges of a complex and rare neurotoxic side effect of CAR-T cell therapy, namely NCSE following status epilepticus.

  View details for DOI 10.1177/19418744211000980

  View details for PubMedCentralID PMC8689529

• Toward platelet transcriptomics in cancer diagnosis, prognosis and therapy British Journal of Cancer Krishnan, A., Thomas, S. 2021

  View details for DOI 10.1038/s41416-021-01627-z

• Portopulmonary Hypertension: From Bench to Bedside Frontiers in Medicine Thomas , C., Ginskii, V., de Jesus Perez, V., Sahay, S. 2020

  View details for DOI 10.3389/fmed.2020.569413

• The Death of George Floyd: Bending the Arc of History Towards Justice for Generations of Children Pediatrics Dreyer, B., Trent, M., et. al. 2020

  View details for DOI 10.1542/peds.2020-009639

• Measuring aspects of high-reliability culture in healthcare settings J Pt Saf Risk Manag Etchegaray, J., Thomas, E. J., Profit, J. 2019

  View details for DOI 10.1177/2516043519838185

• Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis Marinkovich, M. P., et al 2018

  Abstract

  Inflammation is critical to atherogenesis. Psoriasis is a chronic inflammatory skin disease that accelerates atherosclerosis in humans and provides a compelling model to understand potential pathways linking these diseases. A murine model capturing the vascular and metabolic diseases in psoriasis would accelerate our understanding and provide a platform to test emerging therapies. We aimed to characterize a new murine model of skin inflammation (Rac1V12) from a cardiovascular standpoint to identify novel atherosclerotic signaling pathways modulated in chronic skin inflammation. The RacV12 psoriasis mouse resembled the human disease state, including presence of systemic inflammation, dyslipidemia, and cardiometabolic dysfunction. Psoriasis macrophages had a proatherosclerotic phenotype with increased lipid uptake and foam cell formation, and also showed a 6-fold increase in cholesterol crystal formation. We generated a triple-genetic K14-RacV12-/+/Srb1-/-/ApoER61H/H mouse and confirmed psoriasis accelerates atherogenesis (~7-fold increase). Finally, we noted a 60% reduction in superoxide dismutase 2 (SOD2) expression in human psoriasis macrophages. When SOD2 activity was restored in macrophages, their proatherogenic phenotype reversed. We demonstrate that the K14-RacV12 murine model captures the cardiometabolic dysfunction and accelerates vascular disease observed in chronic inflammation and that skin inflammation induces a proatherosclerotic macrophage phenotype with impaired SOD2 function, which associated with accelerated atherogenesis.

  View details for DOI 10.1172/jci.insight.97179

  View details for PubMedCentralID PMC5821196