Medicine and Health Sciences Commons^™

Prophylactic Corticosteroid Use In Patients Receiving Axicabtagene Ciloleucel For Large B-Cell Lymphoma, Olalekan O. Oluwole, Krimo Bouabdallah, Javier Muñoz, Sophie De Guibert, Julie M. Vose, Nancy L. Bartlett, Yi Lin, Abhinav Deol, Peter A. Mcsweeney, Andre H. Goy, Marie José Kersten, Caron A. Jacobson, Umar Farooq, Monique C. Minnema, Catherine Thieblemont, John M. Timmerman, Patrick Stiff, Irit Avivi, Dimitrios Tzachanis, Jenny J. Kim, Zahid Bashir, Jeff Mcleroy, Yan Zheng, John M. Rossi, Lisa Johnson, Lovely Goyal, Tom Van Meerten

Journal Articles: Internal Medicine

ZUMA-1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi-cel), an autologous CD19-directed chimaeric antigen receptor (CAR)-T cell therapy, in refractory large B-cell lymphoma. To reduce treatment-related toxicity, several exploratory safety management cohorts were added to ZUMA-1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end-points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days -5 through -3), 2 × 10⁶ CAR-T cells/kg (day 0) …

Elevated S-Adenosylhomocysteine Induces Adipocyte Dysfunction To Promote Alcohol-Associated Liver Steatosis, Madan Kumar Arumugam, Srinivas Chava, Karuna Rasineni, Matthew C. Paal, Terrence Donohue, Natalia A. Osna, Kusum K. Kharbanda

Journal Articles: Internal Medicine

It has been previously shown that chronic ethanol administration-induced increase in adipose tissue lipolysis and reduction in the secretion of protective adipokines collectively contribute to alcohol-associated liver disease (ALD) pathogenesis. Further studies have revealed that increased adipose S-adenosylhomocysteine (SAH) levels generate methylation defects that promote lipolysis. Here, we hypothesized that increased intracellular SAH alone causes additional related pathological changes in adipose tissue as seen with alcohol administration. To test this, we used 3-deazaadenosine (DZA), which selectively elevates intracellular SAH levels by blocking its hydrolysis. Fully differentiated 3T3-L1 adipocytes were treated in vitro for 48 h with DZA and analysed for …

Natural Recovery By The Liver And Other Organs After Chronic Alcohol Use, Paul G. Thomes, Karuna Rasineni, Viswanathan Saraswathi, Kusum K. Kharbanda, Dahn L. Clemens, Sarah A. Sweeney, Jacy L. Kubik, Terrence M. Donohue, Carol A. Casey

Journal Articles: Internal Medicine

Chronic, heavy alcohol consumption disrupts normal organ function and causes structural damage in virtually every tissue of the body. Current diagnostic terminology states that a person who drinks alcohol excessively has alcohol use disorder. The liver is especially susceptible to alcohol-induced damage. This review summarizes and describes the effects of chronic alcohol use not only on the liver, but also on other selected organs and systems affected by continual heavy drinking-including the gastrointestinal tract, pancreas, heart, and bone. Most significantly, the recovery process after cessation of alcohol consumption (abstinence) is explored. Depending on the organ and whether there is relapse, …

Drug Susceptibility Patterns Of Mycobacterium Tuberculosis From Adults With Multidrug-Resistant Tuberculosis And Implications For A Household Contact Preventive Therapy Trial, Anne-Marie Demers, Soyeon Kim, Sara Mccallum, Kathleen Eisenach, Michael Hughes, Linda Naini, Alberto Mendoza-Ticona, Neeta Pradhan, Kim Narunsky, Selvamuthu Poongulali, Sharlaa Badal-Faesen, Caryn Upton, Elizabeth Smith, N Sarita Shah, Gavin Churchyard, Amita Gupta, Anneke Hesseling, Susan Swindells, Actg A5300/Impaact I2003 Phoenix Feasibility Study Team

Journal Articles: Internal Medicine

BACKGROUND: Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs).

METHODS: As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations …

Lipid Droplet Membrane Proteome Remodeling Parallels Ethanol-Induced Hepatic Steatosis And Its Resolution, Carol A. Casey, Terrence Donohue, Jacy L. Kubik, Vikas Kumar, Michael J. Naldrett, Nicholas T. Woods, Cole P. Frisbie, Mark A. Mcniven, Paul G. Thomes

Journal Articles: Internal Medicine

Lipid droplets (LDs) are composed of neutral lipids enclosed in a phospholipid monolayer, which harbors membrane-associated proteins that regulate LD functions. Despite the crucial role of LDs in lipid metabolism, remodeling of LD protein composition in disease contexts, such as steatosis, remains poorly understood. We hypothesized that chronic ethanol consumption, subsequent abstinence from ethanol, or fasting differentially affects the LD membrane proteome content and that these changes influence how LDs interact with other intracellular organelles. Here, male Wistar rats were pair-fed liquid control or ethanol diets for 6 weeks, and then, randomly chosen animals from both groups were either refed …

High-Throughput Analysis Of Lung Immune Cells In A Combined Murine Model Of Agriculture Dust-Triggered Airway Inflammation With Rheumatoid Arthritis, Rohit Gaurav, Ted R. Mikuls, Geoffrey M. Thiele, Amy J. Nelson, Meng Niu, Chittibabu Guda, James D. Eudy, Austin E. Barry, Todd A. Wyatt, Debra J. Romberger, Michael J. Duryee, Bryant R. England, Jill A. Poole

Journal Articles: Internal Medicine

Rheumatoid arthritis (RA)-associated lung disease is a leading cause of mortality in RA, yet the mechanisms linking lung disease and RA remain unknown. Using an established murine model of RA-associated lung disease combining collagen-induced arthritis (CIA) with organic dust extract (ODE)-induced airway inflammation, differences among lung immune cell populations were analyzed by single cell RNA-sequencing. Additionally, four lung myeloid-derived immune cell populations including macrophages, monocytes/macrophages, monocytes, and neutrophils were isolated by fluorescence cell sorting and gene expression was determined by NanoString analysis. Unsupervised clustering revealed 14 discrete clusters among Sham, CIA, ODE, and CIA+ODE treatment groups: 3 neutrophils (inflammatory, resident/transitional, …

Alcohol-Induced Lysosomal Damage And Suppression Of Lysosome Biogenesis Contribute To Hepatotoxicity In Hiv-Exposed Liver Cells, Moses New-Aaron, Paul G. Thomes, Murali Ganesan, Raghubendra Singh Dagur, Terrence Donohue, Kusum K. Kharbanda, Larisa Y. Poluektova, Natalia A. Osna

Journal Articles: Internal Medicine

Although the causes of hepatotoxicity among alcohol-abusing HIV patients are multifactorial, alcohol remains the least explored “second hit” for HIV-related hepatotoxicity. Here, we investigated whether metabolically derived acetaldehyde impairs lysosomes to enhance HIV-induced hepatotoxicity. We exposed Cytochrome P450 2E1 (CYP2E1)-expressing Huh 7.5 (also known as RLW) cells to an acetaldehyde-generating system (AGS) for 24 h. We then infected (or not) the cells with HIV-1_ADA then exposed them again to AGS for another 48 h. Lysosome damage was assessed by galectin 3/LAMP1 co-localization and cathepsin leakage. Expression of lysosome biogenesis–transcription factor, TFEB, was measured by its protein levels and by …