Translational Medical Research Commons^™

Design Of The Strive-Ipf Trial-Study Of Therapeutic Plasma Exchange, Rituximab, And Intravenous Immunoglobulin For Acute Exacerbations Of Idiopathic Pulmonary Fibrosis, Tejaswini Kulkarni, Gerard Criner, Daniel Kass, Ivan Rosas, Mary Beth Scholand, Daniel Dilling, Ross Summer, Steven Duncan

Division of Pulmonary and Critical Care Medicine Faculty Papers

BACKGROUND: Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) affect a significant proportion of patients with IPF. There are limited data to inform therapeutic strategies for AE-IPF, despite its high mortality. We discuss the rationale and design of STRIVE-IPF, a randomized, multi-center, open-label Phase IIb clinical trial to determine the efficacy of combined therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIG), in comparison to treatment as usual (TAU), among patients with acute IPF exacerbations.

METHODS: The STRIVE-IPF trial will randomize 51 patients among five sites in the United States. The inclusion criteria have been designed to select a study population …

Operative Versus Nonoperative Management For Diverticulitis Complicated By Abscess, Alix Bernholtz, Abbie R. Bauer

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

You K, Bendl R, Taut C, et al. Randomized clinical trial of elective resection versus observation in diverticulitis with extraluminal air or abscess initially managed conservatively. Br J Surg. 2018;105(8):971-979. https://doi.org/10.1002/bjs.10868

for a patient with a recurrent diverticulitis complicated by abscess formation.

Simplifying Treatment From Double-Inhaler To Single-Inhaler Triple Therapy In Patients With Chronic Obstructive Pulmonary Disease, Kelly Yang, Leah Warren

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using

Ferguson GT, Brown N, Compton C, et al. Once-daily single-inhaler versus twice-daily multiple-inhaler triple therapy in patients with COPD: lung function and health status results from two replicate randomized controlled trials. Respir Res. 2020;21(1):131. https://doi.org/10.1186/s12931-020-01360-w

for a patient requesting a simplified therapeutic regimen with equal efficacy for chronic obstructive pulmonary disease (COPD) management.

Effects Of Chaplain Care On Coping With Cancer, Sarah Battiston, Scott L. Baughan

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical case decision report using:

Piderman KM, Radecki CR, Jenkins SM, et al. Hearing and heeding the voices of those with advanced illnesses. Journal of Palliative Care. 2020;35(4):248-255. https://doi.org/10.1177/0825859720928623

for a patient having difficulty coping with cancer

Efficacy Of Observational Care Versus Antibiotic Therapy For Treatment Of Acute Uncomplicated Diverticulitis, Morgan Mooty, Abbie R. Bauer

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

van Dijk ST, Daniels L, Ünlü Ç, et al. Long-Term Effects of Omitting Antibiotics in Uncomplicated Acute Diverticulitis. Am J Gastroenterol. 2018;113(7):1045-1052. https://doi.org/10.1038/s41395-018-0030-y

for a patient with acute uncomplicated diverticulitis.

Avaren-Fc, A Novel Immunotherapeutic, Recruits Nk Cells In B16f10 Melanoma Tumor Tissue, Sreevatsa Vemuri, Katarina Mayer, Nobuyuki Matoba

Posters-at-the-Capitol

Melanoma is the fifth most common cancer in the US, with limited effective immunotherapeutic options available for patients. Avaren-Fc (AvFc) is a novel experimental immunotherapeutic agent with a unique “lectibody” property. It is capable of targeting cancer cells through the selective recognition of high mannose glycans, which are aberrantly overrepresented on the surface of malignant cells. AvFc can interact with circulating effector immune cells equipped with Fc receptors, such as natural killer (NK) cells to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and kill cancer cells. Previous work has shown that AvFc effectively induces ADCC activity against B16F10 cancer cells in vitro …

Promoting Mammography Screenings In African American Women: Media, Church, And Health Providers, Lasonya Little, Debra C. Wallace, K.Jay Poole

Journal of Health Disparities Research and Practice

Due to the underutilization of screening mammography, African American women (AAW) are more likely to experience negative health outcomes after receiving a late-stage breast cancer diagnosis than White Women (WW). The purpose of this article is to examine the roles of the media, health community and the African American church and pastor and their potential impact in AAW screening decisions. Fifteen AAW, ages 45 and older, were invited to participate in a semi-structured interview. Most women agreed the African American pastor and church as well as the health community, and media are an integral part of their lives. Therefore, specific …

An American Medical Economics Phenomenon, Richard Guthmann Md, Mph

Clinical Research in Practice: The Journal of Team Hippocrates

The author reflects on his own experience with medical economics-driven phenomena in healthcare.

Increase In Hnrnpa1 Expression Suffices To Kill Motor Neurons In Transgenic Rats, Xionghao Liu, Tingting Zhang, Qinxue Wu, Cao Huang, Xu-Gang Xia, Hongxia Zhou, Bo Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A dominant mutation in hnRNPA1 causes amyotrophic lateral sclerosis (ALS), but it is not known whether this mutation leads to motor neuron death through increased or decreased function. To elucidate the relationship between pathogenic hnRNPA1 mutation and its native function, we created novel transgenic rats that overexpressed wildtype rat hnRNPA1 exclusively in motor neurons. This targeted expression of wildtype hnRNPA1 caused severe motor neuron loss and subsequent denervation muscle atrophy in transgenic rats that recapitulated the characteristics of ALS. These findings demonstrate that the augmentation of hnRNPA1 expression suffices to trigger motor neuron degeneration and the manifestation of ALS-like phenotypes. …

Renal Disease Rehabilitation And Delaying Dialysis, Spencer Brown, Natalie Sterner

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Greenwood SA, Koufaki P, Mercer TH, et al. Effect of exercise training on estimated GFR, vascular health, and cardiorespiratory fitness in patients with CKD: a pilot randomized controlled trial. Am J Kidney Dis. 2015;65(3):425-434. https://doi.org/10.1053/j.ajkd.2014.07.015

for a patient with non-dialysis CKD interested in slowing the progression toward necessary dialysis.

Slow Surgical Correction Affects More Than Just The Bowels, Emilia M. Clementi

Clinical Research in Practice: The Journal of Team Hippocrates

Reflection on how delayed colostomy reversal affects a patient's mental and physical well-being.

An Ngqd Based Diagnostic Tool For Pancreatic Cancer, Ryan Ketan Ajgaonkar, Bong Lee, Alina Valimukhametova, Anton Naumov, Giridhar Akkaraju

Research Symposium

Background: Pancreatic cancer remains difficult to detect at early stages which contributes to a poor five-yearsurvival rate. Therefore, early detection approaches based on novel technologies should be explored to address this critical health issue. Nanomaterials have recently emerged as frontrunners for diagnostic applications due to their small size in the 1-100 nm range, which facilitates one-on-one interactions with a variety of biomolecules like oligonucleotides and makes them suitable for a plethora of detection and delivery applications. In this work, the presence of specific pancreatic cancer miRNA (pre-miR-132) is detected utilizing the fluorescence properties of highly biocompatible nitrogen-doped graphene quantum dots …

Evaluation Of A Novel Lupus Anticoagulant Assay Designed To Reduce False Positive Results Due To Anticoagulation: A Retrospective Study At A Single Health System, Jessica D. Anderson, Tamara Sabih, Yuying Xing, Lili Zhao, Marc D. Smith

Conference Presentation Abstracts

Introduction: Lupus anticoagulants (LA) are antibodies directed against phospholipids/phospholipid-protein complexes involved in coagulation and are associated with thrombotic events and recurrent fetal loss. There is no gold standard test for LA, therefore at least two LA-specific tests are recommended before excluding LA. Potential testing methods involve dilute Russell viper venom time (dRVVT) and hexagonal phase phospholipid assays (HPPA); however, many of these tests are susceptible to interference with anticoagulant therapy which can lead to false positive results. In this study, we compared the performance of our current HPPA, StaClot LA (SCLA), with a novel assay reported to have relatively minimal …

Neurotropic Manifestations As A Potential Risk Factor For Schizophrenia Following In Utero Exposure To Sars-Cov-2, Mir Ali R Talpur, Omar H. Elsayed, Rif S. El-Mallakh

The University of Louisville Journal of Respiratory Infections

Background: COVID-19 infection is associated with neurologic and psychiatric morbidity that suggests a direct effect of the virus or secondary effect of an inflammatory process. These neuropsychiatric consequences may increase the likelihood of schizophrenia in the offspring of women who become infected with COVID-19 during their pregnancy.

Methods: We performed a directed narrative review of the literature focusing on the proposed pathophysiological processes that lead to schizophrenia and known pathological consequences of COVID-19 infection.

Results: Schizophrenia in adult offspring has been associated with maternal infections during pregnancy by a wide range of respiratory and neurotropic pathogens. Spikes in the incidence …

Interpreting P Values In 2023, Jennifer K. Homa-Bonell

Journal of Patient-Centered Research and Reviews

If recent experiences shared among the biostatistician community are indicative of a sea change in research, then a most-welcome culture shift in dialogue surrounding the proper use and interpretation of the P value, which measures statistical probability, is underway. This editorial strives to offer guidance for researchers who would like to incorporate more comprehensive reporting in their research, namely, a broader discussion that goes beyond looking at the P value by itself and includes effect size estimates, confidence intervals, and clinical implications when interpreting quantitative results. Another evolving development in clinical research is the preferred language when referring …

Calcium Carbonate As A Potential Intervention To Prevent Labor Dystocia: Narrative Review Of The Literature, Sabahat Raees, Marie Forgie, Rita Mitchell, Emily Malloy

Journal of Patient-Centered Research and Reviews

Anecdotally, there are attestations from clinicians of calcium carbonate being used successfully for laboring people experiencing labor dystocia. The goal of this narrative review was to provide a synopsis of pertinent literature on calcium use in obstetrics to explore the potential benefit of calcium carbonate as a simple and low-cost intervention for prevention or treatment of labor dystocia. To answer how calcium and carbonate physiologically contribute to myometrium contractility, we conducted a literature search of English-language peer-reviewed articles, with no year limitation, consisting of the keywords “calcium,” “calcium carbonate,” “calcium gluconate,” “pregnancy,” “hemorrhage,” and variations of “smooth muscle contractility” and …

Shedding Light On Hearing In Coma: Investigating The Applicability Of Functional Near-Infrared Spectroscopy For Assessing Auditory Function And Aiding Prognosis In Patients With Acute Disorders Of Consciousness, Reza Moulavi Ardakani

Electronic Thesis and Dissertation Repository

There is a critical need for a bedside neuroimaging tool to aid in the prediction of functional recovery outcomes for patients with acute disorders of consciousness (DoC) in the early days following severe brain injury. Current neurobehavioral examinations and prognosis tools have limitations in predicting good outcomes, leading to potential mistreatment or premature withdrawal of life support. Functional near-infrared spectroscopy (fNIRS) is a viable candidate for such purposes due to its portability and cost-effectiveness. Auditory processing, viewed as a multi-level and multifaceted brain function, could provide a sensitive and specific marker of residual cognitive function in unresponsive patients. This study …

Professionalism And Moral Injury In A Capitalist Healthcare System, James Peter Meza Md, Phd, Kassem Soufan Md, Michael Francis Do, Abbass Berjaoui Md

Clinical Research in Practice: The Journal of Team Hippocrates

Professionalism cautions against profit while capitalism exists for profit. This case is a structural analysis of capitalism in a clinical setting that reveals physicians to be simultaneously wage laborers and professionals. Capitalism generates profit. Professionalism views profit as a conflict of interest that erodes trust in the doctor-patient relationship. Managing these conflicting values causes moral injury for physicians, which is a driver of physician burnout.

Mechanical Thrombectomy For Intermediate Risk Pulmonary Embolism, James Peter Meza, Marissa Costello Md, Angela Moughni Md, Nicholus Yee Md

Clinical Research in Practice: The Journal of Team Hippocrates

An informed consent article using a set of publications to develop an informed consent conversation for a patient with an acute pulmonary embolism being considered for pulmonary artery thrombolysis.

The Effect Of Kidney Preservation At 10°C With Hemopure And Hydrogen Sulfide Donor, Sodium Thiosulfate, In A Syngeneic Model Of Rat Renal Transplantation, Maria Abou Taka

Electronic Thesis and Dissertation Repository

Kidney transplantation is preferred for patients with end-stage renal disease. The current gold standard for preserving kidneys is static cold storage (SCS) at 4°C in University of Wisconsin (UW) solution. However, SCS contributes to ischemia-reperfusion injury (IRI), which involves cell death and inflammation. Our group showed that SCS of kidneys with hydrogen sulfide donors, like sodium thiosulfate (STS), that reduce tissue injury enhanced kidney survival. Though, there is still a risk of cold renal IRI at 4°C. Recent evidence suggests that preserving organs at 10°C enhanced graft function and survival. Therefore, this thesis will evaluate the effect of 10°C kidney …

On The Respiratory Syncytial Virus Vaccine, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Increased Glucose Availability Sensitizes Pancreatic Cancer To Chemotherapy, Ali Vaziri-Gohar, Jonathan J. Hue, Ata Abbas, Hallie J. Graor, Omid Hajihassani, Mehrdad Zarei, George Titomihelakis, John Feczko, Moeez Rathore, Sylwia Chelstowska, Alexander W. Loftus, Rui Wang, Mahsa Zarei, Maryam Goudarzi, Renliang Zhang, Belinda Willard, Li Zhang, Adam Kresak, Joseph E. Willis, Gi-Ming Wang, Curtis Tatsuoka, Joseph M. Salvino, Ilya Bederman, Henri Brunengraber, Costas A. Lyssiotis, Jonathan R. Brody, Jordan M. Winter

Student Papers, Posters & Projects

Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to chemotherapy. Effective alternative therapies have yet to emerge, as chemotherapy remains the best available systemic treatment. However, the discovery of safe and available adjuncts to enhance chemotherapeutic efficacy can still improve survival outcomes. We show that a hyperglycemic state substantially enhances the efficacy of conventional single- and multi-agent chemotherapy regimens against PDAC. Molecular analyses of tumors exposed to high glucose levels reveal that the expression of GCLC (glutamate-cysteine ligase catalytic subunit), a key component of glutathione biosynthesis, is diminished, which in turn augments oxidative anti-tumor damage by chemotherapy. Inhibition of GCLC phenocopies …

A Review Of Isomirs In Colorectal Cancer, Molly A. Lausten, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

As advancements in sequencing technology rapidly continue to develop, a new classification of microRNAs has occurred with the discovery of isomiRs, which are relatively common microRNAs with sequence variations compared to their established template microRNAs. This review article seeks to compile all known information about isomiRs in colorectal cancer (CRC), which has not, to our knowledge, been gathered previously to any great extent. A brief overview is given of the history of microRNAs, their implications in colon cancer, the canonical pathway of biogenesis and isomiR classification. This is followed by a comprehensive review of the literature that is available on …

Particle Arc Single-Isocenter Stereotactic Radiosurgery Of Multiple Brain Metastases, L Volz, S Mein, T Tessonnier, Peilin Liu, A Mairani, M Durante, Xuanfeng Ding, C Graeff, T Li

Conference Presentation Abstracts

Purpose: To develop spot-scanning proton (SPArc) and heavy ion (SHArc) arc therapy for single-isocenter stereotatic radiosurgery (SISRS) of multiple brain metastases (MBMs). First results achieved with dedicated planning infrastructure are compared to state-of-the -art volumetric modulated photon arc therapy (HA-VMAT). Methods: A multi-institutional collaboration was established to develop bespoke SPArc and SHArc SISRS infrastructure with available research and commercial treatment planning systems. Devised planning and delivery methods considered dedicated energy, spot, and multi-arc selection strategies. SPArc and SHArc (carbon and helium ions) plans were generated for MBM patients exhibiting 3-12 intracranial lesions with GTV volumes between 0.03ccm and 19.8ccm, at …

An Analytic Model Of The External Beam Dose Rate Effect On Immune Cells In Blood Dosimetry, Lili Zhao, Peilin Liu, G Liu, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: Radiation therapy is a double-edged sword with regard to its immunomodulatory effect. It is critical to find how it is affected by dose rate. Thus, we developed an analytic model for calculating the number of immune cells receiving radiation. Methods: Suppose the blood is received radiation by constant dose rate. The blood is one-way flow without circulation in the radiation delivery at a constant velocity. Two kinds of lung treatment regimens were considered standard delivery 2Gy per fx total 30fx and hypo-fractionation SBRT 12 Gy per fx total 5 fx. Two different dose rates were simulated for standard treatment: …

Integrative Analysis Of Metabolome And Methylome Identifies The Correlation Of Aminoacyl-Trna Biosynthesis Metabolitesand Sepsecs Gene Methylation In Huntington’S Disease Brain Tissue, Sangeetha Vishweswaraiah, Ali Yilmaz, Nadia Ashrafi, Nazia Saiyed, Abdulla Khalid, Purvesh R. Koladiya, Xiaobei Pan, Shirin Macias, Uppala Radhakrishna, Stewart F. Graham

Conference Presentation Abstracts

No abstract provided.

Does Proton Arc Therapy Has Potential Clinical Benefits For Hepatocellular Carcinoma?, Peilin Liu, R Dalfsen, M Soukup, Shupeng Chen, Lili Zhao, Z Wang, X S. Gao, Thomas Quinn, Craig Stevens, Rohan Deraniyagala, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: To investigate the potential clinical benefits and dose-averaged Linear Energy Transfer (LETd) sparing, utilizing proton arc plan for Hepatocellular carcinoma (HCC) patients in comparison with Intensity Modulated Proton Therapy (IMPT). Methods: Ten HCC patients have been retrospectively selected. Two planning groups were created: Proton Arc plans using Monaco ver. 6 and the clinical IMPT plan. Both planning groups used the same robustness parameters. The prescription dose is 67.5 Gy (RBE) in 15 fractions/ 66 GyE in 10 fractions of the Clinical Target Volume (CTV) following clinical IMPT plan. Robustness evaluations were performed to ensure target dose coverage. Normal Tissue …

Investigate The Delivery Efficiency Improvement For Sparc Compared To Impt, Peilin Liu, B A. De Jong, S Chang, Lili Zhao, G Liu, Craig Stevens, Rohan Deraniyagala, E W. Korevaar, J A. Langendijk, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: To assess the efficiency improvement of SPArc compared to IMPT in proton clinical operation.Methods: A random clinical operation day at a proton therapy center with a two room system. Aa total of 10 Head & Neck cancer cases treated on Jan 6th, 2021were selected and SPArc plans were generated for all the cases with similar target coverage and dose constraints of organ at risk (OARs). 3% range uncertainties and 3mm setup uncertainties were applied for robust optimization. The log files of clinical IMPT were exported to calculate true treatment delivery time. The machine-specific delivery sequence model was utilized to …

Test-Retest Reliability Of Virtual Reality Devices In Quantifying For Relative Afferent Pupillary Defect, Prithul Sarker, Nasif Zaman, Joshua Ong, Phani Paladugu, Molly Aldred, Ethan Waisberg, Andrew G. Lee, Alireza Tavakkoli

Student Papers, Posters & Projects

Background: The swinging flashlight test (SFT) is one of the most prominent clinical tests for detecting the relative afferent pupillary defect (RAPD). A positive RAPD localizes the lesion to the affected afferent pupil pathway and is a critical part of any ophthalmic exam. Testing for an RAPD, however, can be challenging (especially when small), and there is significant intrarater and interrater variability.

Methods: Prior studies have shown that the pupillometer can improve the detection and measurement of RAPD. In our previous research, we have demonstrated an automatic SFT by utilizing virtual reality (VR), named VR-SFT. We applied our methods to …

A Comprehensive Investigation Of Linear Energy Transfer Optimization Effectiveness In Intensity-Modulated Proton Therapy Via Alternating Direction Method Of Multipliers (Impt Let-Admm), Q Fan, G Liu, Lili Zhao, Xiaoqiang Li, Xuanfeng Ding, S Dai

Conference Presentation Abstracts

Linear energy transfer (LET)-guided optimization in intensity-modulated proton therapy (IMPT) via alternating direction method of multipliers (ADMM) has the potential to improve its biological effectiveness (IMPTLET- ADMM), in which the LET distribution in target can be escalated, while the LET distribution in the organs at risk can be mitigated. This study aims to quantitatively investigate the effectiveness of LET optimization in IMPT via ADMM with different solvers in its iteration loop. Methods: The clinical dose-volume-histogram (DVH) constraint noted dose sub-problem and clinical LET -volume-histogram (LVH) constraint noted LET sub-problem are combined to generate a composite objective function, which is available …