Internal Medicine Commons^™

The Efficacy Of Sequential Biologic Agents In Refractory Rheumatoid Arthritis After Failure Of Initial Dmard And Anti-Tumor Necrosis Factor Therapy, Antonio Giovanni Versace, Caterina Oriana Aragona, Daniela La Rosa, Marianna Chiappalone, Maria Concetta Tringali, Alberta De Gaetano, Charles Frederick Moore Jr., Donatella Sangari, William Neal Roberts, Gianluca Bagnato

Internal Medicine Faculty Publications

Introduction/Objective: The efficacy of biologic therapy in the treatment of rheumatoid arthritis (RA) has been well-established but, in practice, a quarter of patients will either not respond to the first biologic agent or will suffer an adverse event requiring a switch to a different drug. While clinical guidelines exist to help guide therapy and previous studies have examined sequential use of anti-TNF agents, there is little data to inform a multiple switch strategy. Our aim was to measure the efficacy of multiple switches of biologic in severe refractory RA. Methods: We enrolled 111 patients whose therapy with one anti-TNF agent …

Does Anyone Remember "Fingerprints On An X-Ray?", Vincent L. Sorrell

Gill Heart & Vascular Institute Faculty Publications

No abstract provided.

A Step-By-Step Guide To Implementing A Multidisciplinary Endocarditis Team, Sami El-Dalati, Daniel Cronin, James Riddell, Michael Shea, Richard L. Weinberg, Emily Stoneman, Twisha Patel, Kirra Ressler, George Michael Deeb

Internal Medicine Faculty Publications

Over the last several years multiple studies, primarily from European centers have demonstrated the clinical and outcomes benefits of multidisciplinary endocarditis teams. Despite this literature, adoption of this approach to patient care has been slower in the United States. While there is literature outlining the optimal composition of an endocarditis team, there is little information to guide providers as they attempt to transform practice from a fragmented, disjointed process to an efficient, collaborative care model. In this review, the authors will outline the steps they took to create and implement a successful multidisciplinary endocarditis team at the University of Michigan. …

Role Of Serum Amyloid A In Abdominal Aortic Aneurysm And Related Cardiovascular Diseases, Preetha Shridas, Avery C. Patrick, Lisa R. Tannock

Internal Medicine Faculty Publications

Epidemiological data positively correlate plasma serum amyloid A (SAA) levels with cardiovascular disease severity and mortality. Studies by several investigators have indicated a causal role for SAA in the development of atherosclerosis in animal models. Suppression of SAA attenuates the development of angiotensin II (AngII)-induced abdominal aortic aneurysm (AAA) formation in mice. Thus, SAA is not just a marker for cardiovascular disease (CVD) development, but it is a key player. However, to consider SAA as a therapeutic target for these diseases, the pathway leading to its involvement needs to be understood. This review provides a brief description of the pathobiological …

Macrophages Expressing Uncoupling Protein 1 Increase In Adipose Tissue In Response To Cold In Humans, Brian S. Finlin, Hasiyet Memetimin, Amy L. Confides, Beibei Zhu, Philip M. Westgate, Esther E. Dupont-Versteegden, Philip A. Kern

Internal Medicine Faculty Publications

Acute cold induces beige adipocyte protein marker expression in human subcutaneous white adipose tissue (SC WAT) from both the cold treated and contralateral leg, and the immune system regulates SC WAT beiging in mice. Cold treatment significantly increased the gene expression of the macrophage markers CD68 and 86 in SC WAT. Therefore, we comprehensively investigated the involvement of macrophages in SC WAT beiging in lean and obese humans by immunohistochemistry. Cold treatment significantly increased CD163/CD68 macrophages in SC WAT from the cold treated and contralateral legs of lean and obese subjects, and had similar effects on CD206/CD68 macrophages, whereas the …

Characterizing Long Covid: Deep Phenotype Of A Complex Condition, Rachel R. Deer, Madeline A. Rock, Nicole Vasilevsky, Leigh Carmody, Halie Rando, Alfred J. Anzalone, Marc D. Basson, Tellen D. Bennett, Timothy Bergquist, Eilis A. Boudreau, Carolyn T. Bramante, James Brian Byrd, Tiffany J. Callahan, Lauren E. Chan, Haitao Chu, Christopher G. Chute, Ben D. Coleman, Hannah E. Davis, Joel Gagnier, Casey S. Greene, Ramakanth Kavuluru

Institute for Biomedical Informatics Faculty Publications

BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or "long COVID"), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies.

METHODS: The Human Phenotype Ontology …

Adult Spiny Mice (Acomys) Exhibit Endogenous Cardiac Recovery In Response To Myocardial Infarction, Hsuan Peng, Kazuhiro Shindo, Renée R. Donahue, Erhe Gao, Brooke M. Ahern, Bryana M. Levitan, Himi Tripathi, David Powell, Ahmed Noor, Garrett A. Elmore, Jonathan Satin, Ashley W. Seifert, Ahmed K. Abdel-Latif

Physiology Faculty Publications

Complex tissue regeneration is extremely rare among adult mammals. An exception, however, is the superior tissue healing of multiple organs in spiny mice (Acomys). While Acomys species exhibit the remarkable ability to heal complex tissue with minimal scarring, little is known about their cardiac structure and response to cardiac injury. In this study, we first examined baseline Acomys cardiac anatomy and function in comparison with commonly used inbred and outbred laboratory Mus strains (C57BL6 and CFW). While our results demonstrated comparable cardiac anatomy and function between Acomys and Mus, Acomys exhibited a higher percentage of cardiomyocytes displaying …

Biotinylation As A Tool To Enhance The Uptake Of Small Molecules In Gram-Negative Bacteria, Ankit Pandeya, Ling Yang, Olaniyi Alegun, Chamikara Karunasena, Chad Risko, Zhenyu Li, Yinan Wei

Chemistry Faculty Publications

Antibiotic resistance is a major public health concern. The shrinking selection of effective antibiotics and lack of new development is making the situation worse. Gram-negative bacteria more specifically pose serious threat because of their double layered cell envelope and effective efflux systems, which is a challenge for drugs to penetrate. One promising approach to breach this barrier is the “Trojan horse strategy”. In this technique, an antibiotic molecule is conjugated with a nutrient molecule that helps the antibiotic to enter the cell through dedicated transporters for the nutrient. Here, we explored the approach using biotin conjugation with a florescent molecule …

Perspectives On Extended-Release Naltrexone Induction Among Patients Living With Hiv And Opioid Use Disorder: A Qualitative Analysis, Kim A. Hoffman, Robin Baker, Laura C. Fanucchi, Paula J. Lum, Lynn E. Kunkel, Javier Ponce Terashima, Dennis Mccarty, Petra Jacobs, P. Todd Korthuis

Internal Medicine Faculty Publications

BACKGROUND: The CHOICES study randomized participants with HIV and opioid use disorder (OUD) to HIV clinic-based extended-release naltrexone (XR-NTX), which requires complete cessation of opioid use, versus treatment-as-usual (i.e., buprenorphine, methadone). Study participants randomized to XR-NTX were interviewed to assess their experiences with successful and unsuccessful XR-NTX induction.

METHODS: Semi-structured qualitative interviews were completed with a convenience sample of study participants with HIV and OUD (n = 37) randomized to XR-NTX in five HIV clinics between 2018 and 2019. All participants approached agreed to be interviewed. Interviews were digitally recorded, professionally transcribed, and analyzed using thematic analysis.

RESULTS: Participants …

Serum Concentrations Of Legacy And Emerging Per- And Polyfluoroalkyl Substances In The Anniston Community Health Surveys (Achs I And Achs Ii), Michael C. Petriello, M. Abdul Mottaleb, Tara C. Serio, Bharat Balyan, Matthew C. Cave, Marian Pavuk, Linda S. Birnbaum, Andrew J. Morris

Internal Medicine Faculty Publications

Background

Residents of Anniston Alabama were highly exposed to polychlorinated biphenyls (PCBs) due to longstanding manufacturing in the area. The Anniston Community Health Surveys (ACHS I-2005–2007 and II, 2014) have linked these exposures with a variety of deletereous health outcomes. In addition to PCBs, these individuals were likely simultaneously exposed to other persistent organic pollutants including per and polyfluoroalkyl substances (PFAS), which are an emerging class of ubiquitous industrial chemicals that are measurable in the blood of most individuals and have themselves been linked increased risk of some non communicable diseases.

Methods

To characterize PFAS exposures in ACHS I and …

Rapid Response To Mycophenolate Mofetil In Combination With Romiplostim In A Case Of Severe Refractory Immune Thrombocytopenia Post Covid-19 Vaccination, Snigdha Nutalapati, Garima Gupta, Gerhard C. Hildebrandt

Internal Medicine Faculty Publications

Vaccine mediated immune mediated thrombocytopenia (ITP) is exceedingly rare. We present a case of a young female who developed severe refractory ITP with multiple bleeding sites post second dose of COVID-19 vaccination. She was treated with a combination of romiplostim and mycophenolate mofetil that resulted in rapid platelet count recovery.

Euglycemic Diabetic Ketoacidosis Due To Sglt2 Inhibitor In A Patient With Gitelman Syndrome: A Therapeutic Dilemma, Taha Ahmed, Hussain Karimi, Vishwajit Hegde, Samra Haroon Lodhi

Internal Medicine Faculty Publications

Euglycemic diabetic ketoacidosis (DKA) is a rarely reported side effect of sodium-glucose cotransporter-2 inhibitor (SGLT2i) empagliflozin. A 51-year-old female with Gitelman syndrome and type 2 diabetes mellitus (DM) presented with abdominal pain after a recent hospitalization for acute pancreatitis. Her diabetes medications included metformin, pioglitazone, and empagliflozin. Diabetic ketoacidosis was suspected; however, glucose levels were below the cutoff for DKA; therefore, she was diagnosed with euglycemic DKA. Her pancreatitis workup was insignificant. Severe symptomatic hypokalemia despite aggressive repletion limited the management of DKA with insulin infusion therapy. As her ketonemia resolved, she was initiated on subcutaneous insulin with a small …

Androgen Receptor Signaling In Prostate Cancer And Therapeutic Strategies, Aasems Jacob, Rishi Raj, Derek B. Allison, Zin W. Myint

Markey Cancer Center Faculty Publications

Understanding of the molecular mechanisms of prostate cancer has led to development of therapeutic strategies targeting androgen receptor (AR). These androgen-receptor signaling inhibitors (ARSI) include androgen synthesis inhibitor-abiraterone and androgen receptor antagonists-enzalutamide, apalutamide, and darolutamide. Although these medications provide significant improvement in survival among men with prostate cancer, drug resistance develops in nearly all patients with time. This could be through androgen-dependent or androgen-independent mechanisms. Even weaker signals and non-canonical steroid ligands can activate AR in the presence of truncated AR-splice variants, AR overexpression, or activating mutations in AR. AR splice variant, AR-V7 is the most studied among these and …

The Compounding Effect Of Rurality On Health Disparities Among Black Patients With Covid-19, Jessica E. Johnson, Ruchi Bhandari, Allison Lastinger, Rebecca Reece

Journal of Appalachian Health

Background: West Virginia had garnered national attention for its vaccination rollout against coronavirus 2019 (COVID-19). Outcomes of this mostly rural population, however, have been underreported. As the pandemic continues, identifying high risk populations remains important to further epidemiologic information and target vaccines.

Purpose: The objective of this study is to examine the effects of COVID-19 and the influence of race and rurality on hospitalization and outcomes in Appalachians.

Methods: In this retrospective study, data from patients who tested positive and were admitted for COVID-19 and seen within the state’s largest health system (West Virginia University Health System) between March …

Exploring Perceived Importance Of A Novel Emergency Food Program During Covid-19 And Program Recipient Characteristics, Makenzie L. Barr, Kendra Oonorasak, Kristin Hughes, Lauren Batey, Kaela Jackson, Haley Marshall, Tammy Stephenson

Dietetics and Human Nutrition Faculty Publications

Following rising unemployment rates and consequent loss of income due to COVID-19, many people have been seeking meal assistance. This study examines the impact of a community-based free meal distribution program during the pandemic in Kentucky, reviewing characteristics of recipients of the program. Demographics, health behaviors, food insecure classification, and rating of importance of the meal program were collected. Qualitative feedback on the impact of the program was collected via open response. Of the 92 participants using the meal service, the cohort was female, Black, 43 years of age (43.5 ± 15.0 years), with a household income under 30,000 USD …

Long-Term Survival Of Older Patients Hospitalized For Covid-19. Do Clinical Characteristics Upon Admission Matter?, Michał Chojnicki, Agnieszka Neumann-Podczaska, Mikołaj Seostianin, Zofia Tomczak, Hamza Tariq, Jerzy Chudek, Sławomir Tobis, Iwona Mozer-Lisewska, Aleksandra Suwalska, Andrzej Tykarski, Piotr Merks, Sylwia Kropińska, Małgorzata Sobieszczańska, Frank Romanelli, Katarzyna Wieczorowska-Tobis

Pharmacy Practice and Science Faculty Publications

Older adults are particularly susceptible to COVID-19 in terms of both disease severity and risk of death. To compare clinical differences between older COVID-19 hospitalized survivors and non-survivors, we investigated variables influencing mortality in all older adults with COVID-19 hospitalized in Poznań, Poland, through the end of June 2020 (n = 322). In-hospital, post-discharge, and overall 180-day mortality were analyzed. Functional capacity prior to COVID-19 diagnosis was also documented. The mean age of subjects was 77.5 ± 10.0 years; among them, 191 were females. Ninety-five (29.5%) died during their hospitalization and an additional 30 (9.3%) during the post-discharge period …

Cellular Origins Of Egfr-Driven Lung Cancer Cells Determine Sensitivity To Therapy, Fan Chen, Jinpeng Liu, Robert M. Flight, Kassandra J. Naughton, Alexsandr Lukyanchuk, Abigail R Edgin, Xiulong Song, Haikuo Zhang, Kwok-Kin Wong, Hunter N. B. Moseley, Chi Wang, Christine F. Brainson

Toxicology and Cancer Biology Faculty Publications

Targeting the epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors (TKIs) is one of the major precision medicine treatment options for lung adenocarcinoma. Due to common development of drug resistance to first- and second-generation TKIs, third-generation inhibitors, including osimertinib and rociletinib, have been developed. A model of EGFR-driven lung cancer and a method to develop tumors of distinct epigenetic states through 3D organotypic cultures are described here. It is discovered that activation of the EGFR T790M/L858R mutation in lung epithelial cells can drive lung cancers with alveolar or bronchiolar features, which can originate from alveolar type 2 (AT2) cells …

Engaging Patients With Late-Stage Non-Small Cell Lung Cancer In Shared Decision Making About Treatment, Ronald E. Myers, Shailesh M. Advani, Pamela Myers, Preethi Selvan, Gregory Garber, Brooke Worster, Neal Flomenberg, Andrew Chapman, Ralph Zinner

Internal Medicine Faculty Publications

Few treatment decision support interventions (DSIs) are available to engage patients diagnosed with late-stage non-small cell lung cancer (NSCLC) in treatment shared decision making (SDM). We designed a novel DSI that includes care plan cards and a companion patient preference clarification tool to assist in shared decision making. The cards answer common patient questions about treatment options (chemotherapy, chemotherapy plus immunotherapy, targeted therapy, immunotherapy, clinical trial participation, and supportive care). The form elicits patient treatment preference. We then conducted interviews with clinicians and patients to obtain feedback on the DSI. We also trained oncology nurse educators to implement the prototype. …

The Covid-19 Assessment For Survival At Admission (Casa) Index: A 12 Months Observational Study, Gianluca Bagnato, Daniela La Rosa, Carmelo Ioppolo, Alberta De Gaetano, Marianna Chiappalone, Natalia Zirilli, Valeria Viapiana, Maria Concetta Tringali, Simona Tomeo, Caterina Oriana Aragona, Francesca Napoli, Sara Lillo, Natasha Irrera, William Neal Roberts, Egidio Imbalzano, Antonio Micari, Elvira Ventura Spagnolo, Giovanni Squadrito, Sebastiano Gangemi, Antonio Giovanni Versace

Internal Medicine Faculty Publications

Objective: Coronavirus disease 2019 (COVID-19) is a disease with a high rate of progression to critical illness. However, the stratification of patients at risk of mortality is not well defined. In this study, we aimed to define a mortality risk index to allocate patients to the appropriate intensity of care.

Methods: This is a 12 months observational longitudinal study designed to develop and validate a pragmatic mortality risk score to stratify COVID-19 patients aged ≥18 years and admitted to hospital between March 2020 and March 2021. Main outcome was in-hospital mortality.

Results: 244 patients were included in the study (mortality …

Longitudinal Cognitive Performance Of Alzheimer's Disease Neuropathological Subtypes, Madeline Uretsky, Laura E. Gibbons, Shubhabrata Mukherjee, Emily H. Trittschuh, David W. Fardo, Patricia A. Boyle, C. Dirk Keene, Andrew J. Saykin, Paul K. Crane, Julie A. Schneider, Jesse Mez

Sanders-Brown Center on Aging Faculty Publications

Introduction: Alzheimer's disease (AD) neuropathological subtypes (limbic predominant [lpAD], hippocampal sparing [HpSpAD], and typical [tAD]), defined by relative neurofibrillary tangle (NFT) burden in limbic and cortical regions, have not been studied in prospectively characterized epidemiological cohorts with robust cognitive assessments.

Methods: Two hundred ninety-two participants with neuropathologically confirmed AD from the Religious Orders Study and Memory and Aging Project were categorized by neuropathological subtype based on previously specified diagnostic criteria using quantitative regional NFT counts. Rates of cognitive decline were compared across subtypes using linear mixed-effects models that included subtype, time, and a subtype-time interaction as predictors and four cognitive …

A Case Report Of Metastatic Castration-Resistant Prostate Cancer Harboring A Pten Loss, Zin W. Myint, Derek B. Allison, Carleton S. Ellis

Internal Medicine Faculty Publications

The treatment landscape of metastatic castration-resistant prostate cancer (mCRPC) has dramatically improved over the last decade; however, patients with visceral metastases are still faced with poor outcomes. Phosphatase and tensin homolog (PTEN) loss is observed in 40%–60% of mCRPC patients and is also associated with a poor prognosis. Several PI3K/AKT/mTOR pathway inhibitors have been studied, with disappointing anti-tumor activity. Here, we present a case of a patient with heavily treated mCRPC who had a modest tumor response to concurrent carboplatin, abiraterone acetate/prednisone, and liver-directed radiation therapy. We discuss the potential rationale supporting the use of this combination therapy …

Rapid 3d Reconstruction Guided Embolization For Catastrophic Bleeding Following Vacuum Assisted Breast Biopsy; A Case Report And Review Of The Literature, Martin Halicek, Chenghao Qian, Driss Raissi, Xiaoqin Wang, Yevgen Chornenkyy, William B. Bates, Michael Winkler

Radiology Faculty Publications

The most clinically significant complication associated with stereotactic core needle biopsy of the breast is hematoma formation, which only occurs in less than 1% of biopsies and may require treatment. Cases of uncontrollable bleeding, refractory to repeated compression, resulting from biopsy are exceedingly rare. We present a case of catastrophic, uncontrollable bleeding and large hematoma formation resulting from stereotactic vacuum-assisted breast biopsy of a breast mass identified in screening mammography. Percutaneous embolization was planned and guided using 3D reconstructions from computed tomographic angiography, and bleeding was successfully controlled with micro-coil embolization.

Hiv Infection And The Risk Of World Health Organization-Defined Sudden Cardiac Death, Matthew S. Freiberg, Meredith S. Duncan, Charles Alcorn, Chung-Chou H. Chang, Suman Kundu, Asri Mumpuni, Emily K. Smith, Sarah Loch, Annie Bedigian, Eric Vittinghoff, Kaku So-Armah, Priscilla Y. Hsue, Amy C. Justice, Zian H. Tseng

Biostatistics Faculty Publications

Background

People living with HIV have higher sudden cardiac death (SCD) rates compared with the general population. Whether HIV infection is an independent SCD risk factor is unclear.

Methods and Results

This study evaluated participants from the Veterans Aging Cohort Study, an observational, longitudinal cohort of veterans with and without HIV infection matched 1:2 on age, sex, race/ethnicity, and clinical site. Baseline for this study was a participant's first clinical visit on or after April 1, 2003. Participants were followed through December 31, 2014. Using Cox proportional hazards regression, we assessed whether HIV infection, CD4 cell counts, and/or HIV viral …

Bone Quality And Fractures In Women With Osteoporosis Treated With Bisphosphonates For 1 To 14 Years, Hartmut H. Malluche, Jin Chen, Florence Lima, Lucas J. Liu, Marie-Claude Monier-Faugere, David A. Pienkowski

Internal Medicine Faculty Publications

Oral bisphosphonates are the primary medication for osteoporosis, but concerns exist regarding potential bone-quality changes or low-energy fractures. This cross-sectional study used artificial intelligence methods to analyze relationships among bisphosphonate treatment duration, a wide variety of bone-quality parameters, and low-energy fractures. Fourier transform infrared spectroscopy and histomorphometry quantified bone-quality parameters in 67 osteoporotic women treated with oral bisphosphonates for 1 to 14 years. Artificial intelligence methods established two models relating bisphosphonate treatment duration to bone-quality changes and to low-energy clinical fractures. The model relating bisphosphonate treatment duration to bone quality demonstrated optimal performance when treatment durations of 1 to 8 …

Letter To Editor Regarding The Ocean Study, Barbara P. Yawn, Barry Make, David M. Mannino, Fernando J. Martinez, Meilan K. Han

Preventive Medicine and Environmental Health Faculty Publications

No abstract provided.

Management Of Large Cell Neuroendocrine Carcinoma, Virginia Corbett, Susanne M. Arnold, Lowell B. Anthony, Aman Chauhan

Internal Medicine Faculty Publications

Background: Large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive cancer with a dismal prognosis. The majority of cases occur in the lung and the gastrointestinal tract; however, it can occur throughout the body. Recently advances in the understanding of the molecular underpinnings of this disease have paved the way for additional novel promising therapies. This review will discuss the current best evidence for management of LCNEC and new directions in the classification and treatment of this rare disease.

Methods: We performed a PubMed search for “Large cell neuroendocrine carcinoma” and “High grade neuroendocrine carcinoma.” All titles were screened for …

A Randomized Controlled Trial To Determine Whether Beta-Hydroxy-Beta-Methylbutyrate And/Or Eicosapentaenoic Acid Improves Diaphragm And Quadriceps Strength In Critically Ill Mechanically Ventilated Patients, Gerald S. Supinski, Paul F. Netzel, Philip M. Westgate, Elizabeth A. Schroder, Lin Wang, Leigh Ann Callahan

Internal Medicine Faculty Publications

BACKGROUND: Intensive care unit acquired weakness is a serious problem, contributing to respiratory failure and reductions in ambulation. Currently, there is no pharmacological therapy for this condition. Studies indicate, however, that both beta-hydroxy-beta-methylbutyrate (HMB) and eicosapentaenoic acid (EPA) increase muscle function in patients with cancer and in older adults. The purpose of this study was to determine whether HMB and/or EPA administration would increase diaphragm and quadriceps strength in mechanically ventilated patients.

METHODS: Studies were performed on 83 mechanically ventilated patients who were recruited from the Medical Intensive Care Units at the University of Kentucky. Diaphragm strength was assessed as …

Intravesical Cd74 And Cxcr4, Macrophage Migration Inhibitory Factor (Mif) Receptors, Mediate Bladder Pain, Shaojing Ye, Fei Ma, Dlovan F. D. Mahmood, Katherine L. Meyer-Siegler, Raymond E. Menard, David E. Hunt, Lin Leng, Richard Bucala, Pedro L. Vera

Physiology Faculty Publications

BACKGROUND: Activation of intravesical protease activated receptor 4 (PAR4) leads to release of urothelial macrophage migration inhibitory factor (MIF). MIF then binds to urothelial MIF receptors to release urothelial high mobility group box-1 (HMGB1) and elicit bladder hyperalgesia. Since MIF binds to multiple receptors, we investigated the contribution of individual urothelial MIF receptors to PAR4-induced HMGB1 release in vivo and in vitro and bladder pain in vivo.

METHODOLOGY/PRINCIPAL FINDINGS: We tested the effect of intravesical pre-treatment with individual MIF or MIF receptor (CD74, CXCR4, CXCR2) antagonists on PAR4-induced HMGB1 release in vivo (female C57/BL6 mice) and in vitro (primary …

Innate Immune Activation By Checkpoint Inhibition In Human Patient-Derived Lung Cancer Tissues, Teresa W. M. Fan, Richard M. Higashi, Huan Song, Saeed Daneshmandi, Angela L. Mahan, Matthew S. Purdom, Therese J. Bocklage, Thomas A. Pittman, Daheng He, Chi Wang, Andrew N. Lane

Center for Environmental and Systems Biochemistry Faculty Publications

Although Pembrolizumab-based immunotherapy has significantly improved lung cancer patient survival, many patients show variable efficacy and resistance development. A better understanding of the drug’s action is needed to improve patient outcomes. Functional heterogeneity of the tumor microenvironment (TME) is crucial to modulating drug resistance; understanding of individual patients’ TME that impacts drug response is hampered by lack of appropriate models. Lung organotypic tissue slice cultures (OTC) with patients’ native TME procured from primary and brain-metastasized (BM) non-small cell lung cancer (NSCLC) patients were treated with Pembrolizumab and/or beta-glucan (WGP, an innate immune activator). Metabolic tracing with ¹³C₆-Glc/ …

Serum Renin And Major Adverse Kidney Events In Critically Ill Patients: A Multicenter Prospective Study, Alexander H. Flannery, Victor M. Ortiz-Soriano, Xilong Li, Fabiola G. Gianella, Robert D. Toto, Orson W. Moe, Prasad Devarajan, Stuart L. Goldstein, Javier A. Neyra

Pharmacy Practice and Science Faculty Publications

BACKGROUND: Preliminary studies have suggested that the renin-angiotensin system is activated in critical illness and associated with mortality and kidney outcomes. We sought to assess in a larger, multicenter study the relationship between serum renin and Major Adverse Kidney Events (MAKE) in intensive care unit (ICU) patients.

METHODS: Prospective, multicenter study at two institutions of patients with and without acute kidney injury (AKI). Blood samples were collected for renin measurement a median of 2 days into the index ICU admission and 5-7 days later. The primary outcome was MAKE at hospital discharge, a composite of mortality, kidney replacement therapy, or …