Translational Medical Research Commons^™

A Fully-Automated, Deep Learning-Based Framework For Ct-Based Localization, Segmentation, Verification And Planning Of Metastatic Vertebrae, Tucker Netherton, Tucker James Netherton

Dissertations and Theses (Open Access)

Palliative radiotherapy is an effective treatment for the palliation of symptoms caused by vertebral metastases. Visible evidence of disease is localized on medical images as part of the treatment planning process. However, complicating factors such as time pressures, anatomic variants in the spine, and similarities in adjacent vertebrae are associated with wrong level treatments of the spine. In addition, erroneous manual contouring of anatomic structures is a major failure mode in radiotherapy treatment planning.

The purpose of this study is to mitigate the challenges associated with treatment planning of the spine by automating the treatment planning process for three-dimensional conformal …

Non-Selective Primary Human Tumor Cell Line Generation From Surgical Resections To Be Paired With Flash Frozen And Paraffin Embedded Tissue: Advancements In Democratizing Translational Research Materials To Rural Institutions, Jennifer Hawkins, Rebecca Russell, Logan M. Lawrence, Amrita Valluri, Jessica Wellman, Krista Denning

Marshall Journal of Medicine

Translational cancer research relies on the availability of human patient tissue demonstrating the specific disease process under investigation. Biobanks of human tissue have historically been and remain to date the primary access point for cancer research samples. Biorepositories routinely supply researchers with varying sample types for use in biomedical studies; most commonly formalin-fixed and paraffin-embedded (FFPE) tissue, or fresh snap-frozen tissue. In conjunction with preserved tissue samples, viable tumor cell lines derived from patient tissue have emerged to be a new gold standard in cancer research particularly in drug discovery and functional prognostic assays. Tissue banks providing these samples are …

Streptococcus Anginosus Lung Infection And Empyema: A Case Report And Review Of The Literature, Nishita Tripathi, Kuldeep Ghosh, Anupama Raghuram

The University of Louisville Journal of Respiratory Infections

Streptococcus milleri group (SMG) also referred to as the Streptococcus anginosus group. These are Gram-positive, variable hemolysis, catalase negative, microaerophilic, non-motile facultative anaerobes which have been known to cause abscesses in humans. We report a case of empyema caused by Streptococcus anginosus in a patient with an unresolved pneumonia for over a month. In early October 2018, the patient presented to an emergency room with the complaints of shortness of air, productive cough, chills, subjective fever and weight loss for 4 weeks. A chest X-ray revealed a left lower lobe pneumonia. He was treated with 250 mg of azithromycin for …

Characteristics And Outcomes Of Bacteremic Pneumococcal Pneumonia Of Patients With And Without Hiv Infection In Argentina, Alejandra González

The University of Louisville Journal of Respiratory Infections

Streptococcus pneumoniae is the main causative agent of pneumonia, with a 10 to 25 percent rate of isolation in blood cultures. Controversies exist regarding the prognostic impact of a history of human immunodeficiency virus (HIV) infection on community-acquired pneumonia.

The aim of our work was to analyze and compare the clinical presentation, radiological findings and progression of pneumococcal pneumonia in patients infected with and not infected with HIV. We retrospectively analyzed adult patients with positive blood cultures for Streptococcus pneumoniae and clinical and radiological findings compatible with pneumonia in the period between January 2012 and May 2017. Age, sex, comorbidities, …

Invasive Pneumococcal Serotype 3 Disease Despite Pneumococcal Polysaccharide Vaccine-23, B. Frank Parker Jr, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

Pneumococcal disease has a high global morbidity and mortality. We report a case of a 63-year old female with a history of vaccination with pneumococcal polysaccharide vaccine-23 (PPSV-23) who was transferred to a tertiary care facility with fever and seizures due to an unknown etiology. The diagnosis of invasive pneumococcal disease (IPD) was based the identification of Streptococcus pneumoniae in the blood (culture; serogroup 3) and cerebrospinal fluid (antigen), and the finding of purulence under pressure at craniotomy. The pneumococcal vaccine should provide protection from IPD. The findings reported here display that IPD can overcome immunity proffered by the pneumococcal …

To Preprint Or Not To Preprint, Forest W. Arnold, Kimberley A. Buckner, Alex Glynn, Jessica Petrey, Jose Bordon

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Assessing Pre-Exposure Prophylaxis Screening And Need Among Men Who Have Sex With Men And Transgender Persons Of Color: A Mixed Methods Case Study Of The Impact Dmv Demonstration Project, Brittany C. Wilbourn

Doctor of Philosophy in Translational Health Sciences Dissertations

Men who have sex with men (MSM) and transgender persons of color experience disproportionate, multi-level HIV risks. Pre-exposure prophylaxis (PrEP) is an evidence-based HIV prevention strategy; however, access to PrEP has been limited among this population. PrEP demonstration projects that target MSM and transgender persons and test the implementation of PrEP in real-world settings are underway. However, PrEP demonstration projects specific to MSM and transgender persons of color are limited and most demonstration projects do not consider the impact of the implementation process or organization contextual characteristics on PrEP outcomes. The Improve Measurable Participation and Access to Care and Treatment …

Diagnosis And Management Of Adolescents With Polycystic Ovary Syndrome In Primary Care: A Mixed Method Study To Explore Provider Behaviors And Barriers And Facilitators To Practice, J. Leocadia Conlon

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder in women of reproductive age, associated with complications of metabolic, reproductive, and psychological health. Adolescence is an optimal time for early identification of PCOS in order to mitigate long-term health risks. Pediatric primary care providers (pedPCPs) are the first-line for early identification and coordination of longterm comprehensive management. Limited information exists to describe how PCOS is addressed in primary care and if adolescent-specific guidelines are applied.

Objectives: Describe practice behaviors of pedPCPs in the diagnosis and management of PCOS, and identify barriers and facilitators to inform future interventions to optimize …

Pvn Activity In Cardiac Sympathetic Afferent Reflex (Csar) Control And Cardiovascular Function, Shane H. Boomer

Honors Thesis

Regulation of blood pressure is essential in bodily health. Hypertension and hypotension can be associated with varying diseases that could potentiate further disease. From this, understanding the mechanisms that regulate blood pressure is important within medicine. In my study, I will be focusing on a cardiovascular reflex that is less well understood, the cardiac sympathetic afferent reflex (CSAR). In particular, this work will examine sex differences in this reflex in overall function and in the involvement of an area of the brain called the paraventricular nucleus (PVN). We will test the hypothesis that there will be a significant difference between …

Translating Assessments Into Practice Using Principles Of Patient-Centered Measurement: An Exemplar Using The Coma Recovery Scale-Revised, Jennifer Ann Craft Weaver

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Disorders of consciousness (DoC) include different states (e.g., comatose, vegetative state/unresponsive wakefulness syndrome, minimally conscious state (MCS), and emerging minimally conscious state (eMCS)) following a severe brain injury. Yet, effective communication about treatment of patients with DoC is often inhibited because family caregivers and rehabilitation practitioners do not interpret recovery of consciousness in the same way (Epstein & Street, 2007; Weaver et al., 2018). Because a person may remain in a disordered state of consciousness for as long as two decades and receive multiple episodes of rehabilitation during that time, ensuring clear communication among family caregivers and rehabilitation practitioners …

Combinatorial Use Of Both Epigenetic And Non-Epigenetic Mechanisms To Efficiently Reactivate Hiv Latency, Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

The persistence of latent HIV provirus pools in different resting CD4+ cell subsets remains the greatest obstacle in the current efforts to treat and cure HIV infection. Recent efforts to purge out latently infected memory CD4+ T-cells using latency-reversing agents have failed in clinical trials. This review discusses the epigenetic and non-epigenetic mechanisms of HIV latency control, major limitations of the current approaches of using latency-reversing agents to reactivate HIV latency in resting CD4+ T-cells, and potential solutions to these limitations.

International Respiratory Infections Society Covid Research Conversations: Podcast 3 With Dr. Antoni Torres, Julio A. Ramirez, Antoni Torres

The University of Louisville Journal of Respiratory Infections

Section(s) Topics

1–4 Introductions

5 “Spanish” influenza

6–9 Dr. Torres’ personal thoughts and experiences

10 COVID-19 hospitalizations in Barcelona

11 A threatening phone call

12–13 Origin of the CIBERESUCICOVID project

14 Baseline characteristics

15 Bloodwork at hospital admission; ICU admission vs. day 3

16 Treatments

17 Complications

18 Outcomes related to interventions

19 Viral RNA load in plasma associated with critical illness and dysregulated response

20 Follow-up with health care workers

21 Medical education

22 Conclusions

23–26 Interleukin 6

27–29 Ventilatory approach

30–33 Post-COVID syndrome

34–38 Impact on health care workers

39–41 Holidays and COVID-19 infection

42–43 New paradigm for …

A New Chapter In The Life Of The Journal, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

A Transition Of Uljri Leadership, Forest W. Arnold, Jose Bordon

The University of Louisville Journal of Respiratory Infections

No abstract provided.

International Respiratory Infections Society Covid Research Conversations: Podcast 2 With Dr. Michael S. Niederman And Dr. Edward J. Schenck, Julio A. Ramirez, Michael S. Niederman, Edward J. Schenck

The University of Louisville Journal of Respiratory Infections

Section(s) Topics

1–4 Introductions

5 COVID-19 in New York City

6–7 Telemedicine, long-term sequelae

8 Development of a multi-disciplinary ICU team

9–10 Treatment of ARDS, COVID-19 pathogenesis

11–12 Prioritizing treatment at research

13 Challenges in tracing the natural history of severe COVID-19

14–15 Experience with mechanically ventilated patients; non-pulmonary organ failure

16–17 Mapping COVID-19 trajectories by SOFA score

18–20 Findings: additive organ dysfunction, improving vs. worsening trajectory

21 ARDS therapeutic approaches

22 Clinical trials involving Cornell

23–25 Lessons learned: patient care, research, education, caring for critical care workers

26–30 2021 predictions: improved therapies and research, endemic COVID-19, vaccines

31–33 Prioritizing …

Defining Early And Late Clinical Outcomes In Patients With Sars-Cov-2 Pneumonia, Julio A. Ramirez, Jose Bordon, Rodrigo Cavallazzi, Stephen P. Furmanek, Jiapeng Huang, Timothy L. Wiemken, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.

H1n1 Influenza Virus (Swine Flu): A Comprehensive Insight Into Escalating Catch-22 Scenarios, Muhammad Shahzaib, Ehsan Ul Haq

The University of Louisville Journal of Respiratory Infections

Introduction: Viruses have always been a major cause of various disastrous pandemics in mankind’s history. H1N1 became a threat when its original strain was first discovered back in the swine flu pandemic of 2009. It became highly catastrophic on a large scale because none of the therapeutic interventions and methodologies that were already present at the time were effective against the virus.

Methods: A vast amount of literature and research is available regarding H1N1 influenza from different reputable sources online. The data were gathered with the contrasting and relative situations of 1918 and 2009 pandemics in mind. The overall extracted …

Ap-1 And Nf-Κb Synergize To Transcriptionally Activate Latent Hiv Upon T-Cell Receptor Activation., Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Latent HIV-1 proviruses are capable of reactivating productive lytic infection, but the precise molecular mechanisms underlying emergence from latency are poorly understood. In this study, we determined the contribution of the transcription factors NF-κB, NFAT, and AP-1 in the reactivation of latent HIV following T-cell receptor (TCR) activation using Jurkat T-cell clones harboring single latent HIV proviruses. Our findings demonstrate that during reactivation from latency, NF-κB enhances HIV transcription while NFAT inhibits it by competing with NF-κB for overlapping binding sites on the HIV long terminal repeat (LTR). We have also demonstrated for the first time the molecular contribution of …

International Respiratory Infections Society Covid Research Conversations: Podcast 1 With Dr. Francesco Blasi, Julio A. Ramirez Md, Francesco Blasi Md, Phd

The University of Louisville Journal of Respiratory Infections

Section(s) Topics

1–2 Introductions

3 Foundations of best practice

4 COVID-19 as stimulus for innovation

5 Adapting and evolving therapeutic approach

6 Age and comorbidities as risk factors

7 Over-capacity ICU

8 Adapting the ER for COVID-19

9 Training personnel for COVID-19

10 Psychological support, healthcare heroes, and COVID fatigue

11 Increased oxygen requirement

12–13 Milan’s multi-disciplinary unit

14 Standardizing respiratory support measures

15 Nutrition, sedation, and life support

16 CPAP successes and failures

17 Prone and lateral positioning of patients on CPAP

18 Different COVID-19 phenotypes?

19 Thromboembolism risk score, age, and comorbidities

20 Cardiorespiratory considerations: hypertension, echocardiography

21 …

An Update On The Leading Covid-19 Vaccines, Ahmed A. Eladely, Javaria Anwer Mbbs, Ashwini Gotimukul Mbbs, Manish Kc Mbbs, Jessica Petrey Msls, Alex Glynn Ma, Ruth M. Carrico Phd, Dnp, Julio A. Ramirez Md

The University of Louisville Journal of Respiratory Infections

We reviewed the COVID-19 vaccines that reached phase III of clinical development. For each of the 10 vaccines identified, we described the technology used for vaccine development, the available data from phase III clinical trials, data on vaccine safety, and the role of new SARS-CoV-2 variants on vaccine efficacy.

Detection And Profiling Of Human Coronavirus Immunoglobulins In Critically Ill Coronavirus Disease 2019 Patients, Douglas Fraser

Data and Test Instruments

No abstract provided.

Chloroquine: Autophagy Inhibitor, Antimalarial, Bitter Taste Receptor Agonist In Fight Against Covid-19, A Reality Check?, Pawan Sharma, Kielan D. Mcalinden, Saeid Ghavami, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

The recent SARS-CoV-2 pandemic poses one of the greatest challenges to modern medicine. Therefore, identification of new therapeutic strategies seems essential either based on novel vaccines or drugs or simply repurposing existing drugs. Notably, due to their known safety profile, repurposing of existing drugs is the fastest and highly efficient approach to bring a therapeutic to a clinic for any new indication. One such drug that has been used extensively for decades is chloroquine (CQ, with its derivatives) either for malaria, lupus and rheumatoid arthritis. Accumulating body of evidence from experimental pharmacology suggests that CQ and related analogues also activate …

Impact Of A Multidisciplinary Group On Management Of Patent Foramen Ovale In Cryptogenic Stroke And Outcome Measures: A Retrospective Study, Laura Meissner, Diana L. Tzeng, Md

Phase 1

Patent foramen ovale (PFO) is a common cardiac abnormality present in roughly 25% of the adult population. Although typically benign, patients with a PFO account for 50% of the population of cryptogenic stroke, an ischemic stroke with an unknown cause. Guidelines suggest closure in patients with a cryptogenic stroke found to have a PFO; however, it is unclear whether medical treatment should be given to all patients, regardless of PFO closure, and data is limited on the treatment outcomes. This retrospective chart analysis of 80 patients with a cryptogenic stroke found to have a PFO will investigate the criteria a …

Genetic Profiling Of Cell Types In The Pathogenesis Of Nonalcoholic Steatohepatitis (Nash), Yanki Yarman, Raj Vadigepalli

Phase 1

NASH is the progressive form of non-alcoholic fatty liver disease (NAFLD) which affects 25% of adults in the US. We are interested in identifying genetic markers for specific cell populations in the liver and hypothesize that cells undergo genetic reprogramming to handle the molecular stresses of the NASH disease state.

Using previously published single-cell RNA sequencing datasets from mouse liver whole tissue, we identified the top 25 most highly variable genes per cell type in NASH liver tissue. Using R-programming language, datasets from both healthy and diseases livers were deconvoluted, normalized, linearized and dimensionally reduced to create a 3D map …

Evaluating Barriers To Clinical Trial Enrollment In Head And Neck Surgical Oncology, Gregory Schneider, Emily Sagalow, Kealan Hobelmann, Md, Richard Goldman, Md, David Cognetti, Md, Joseph M. Curry, Md, Adam Luginbuhl, Md

Phase 1

Introduction and Objectives: Clinical trials are an important focus in academic otolaryngology practices, but busy practices may pose difficulty for identification and enrollment of patients eligible for trials. We will identify barriers to enrollment from the perspective of both head and neck surgical oncologists and their patients.

Methods: Patients who were eligible for any of the eight clinical trials offered at Jefferson between August and November 2020 were identified. We utilized an Epic EMR phrase to capture if a trial was offered or not and why, whether a patient refused enrollment and why, and patient wait time.

Results: During the …

Reduced Recovery Times With Total Intravenous Anesthesia In Patients With Obstructive Sleep Apnea, Leonard Estephan, Matthew Stewart, Maurits Boon, Colin Huntley

Phase 1

Introduction: There are currently no specific anesthetic guidelines for patients with obstructive sleep apnea (OSA) undergoing upper airway surgery. Two consistently utilized anesthetic approaches during such procedures include inhalational gas anesthesia and total intravenous anesthesia (TIVA), however whether either is more efficacious remains undefined. We hypothesize that administration of TIVA will lead to reduced post-operative recovery time in patients with comorbid OSA undergoing upper airway surgery.

Methods: A retrospective chart review was performed for patients with comorbid OSA that underwent surgery (upper airway stimulation, nasal surgery, palate surgery) between January 2019 and December 2019. Included patients received either inhaled …

A Comparative Analysis Of Anterior & Lateral Cranial Base Csf Leaks, Rahul Alapati, Glen D. Souza, Md, Prachi Patel, Chandala Chitguppi, Md, Rashiqah Syed, Tawfiq Khoury, Md, Mindy R. Rabinowitz, Md, Christopher J. Farrell, Md, Elina Toskala, Md, Phd, Marc R. Rosen, Md, James J. Evans, Md, Gurston Nyquist, Md

Phase 1

Introduction

The optimal strategy for management of Idiopathic Intracranial Hypertension (IIH) in anterior and lateral cranial base meningoencephaloceles remains debated. The purpose of this study is to present a comparison of the surgical management of anterior and lateral cranial base meningoencephalocele and a treatment algorithm for the diagnosis and management of IIH in this patient population.

Methods

Retrospective study of 109 patients who underwent anterior or lateral CSF leak repair at TJU from 2004-2020. Epic & RedCap were utilized to record data. Patient demographics, presenting symptoms, imaging, Beta-2 Transferring testing, surgery, repair, and post-op data were collected. Two-sided Chi-squared tests …

Comparison Of Endovascular Therapy Versus Medical Therapy In The Management Of Descending Thoracic Aortic Dissection, Eli Cehelyk, Babak Abai, Md

Phase 1

Introduction: This retrospective review aimed to compare clinical outcomes between patients with descending aortic dissections, with and without organ malperfusion, who were managed with thoracic endovascular aortic repair (TEVAR) or best medical therapy (BMT).

Methods: Thirty-eight patients diagnosed with descending aortic dissections between 2013 and 2020 were identified for analysis. Patients with dissection secondary to trauma and death unrelated to cardiothoracic pathology were excluded. Participants were divided into three groups based on their management: TEVAR (without side branch stenting), TEVAR+ (with additional branch stenting) and BMT. The primary outcome measure was length of hospital stay (LOS) and statistics were analyzed …

Otologic Opioid Usage And Pain Control In The Postoperative Period, Matthew Stewart, Eric Mastrolonardo, Joann Butkus, Raphael Banoub, Md, Tingting Zhan, Phd, Sophia Dang, Md, David Cognetti, Md, Rebecca Chiffer, Md, Thomas Wilcox, Md

Phase 1

Introduction: Patients’ unused prescription opioids can be diverted and increase the overall opioid burden on society. Therefore, otolaryngologists can reduce opioid influx by minimizing excess tablets in opioid prescriptions. We hypothesize that otology patients at TJUH receive more opioid tablets than needed to effectively manage postoperative pain.

Methods: Patients ages ≥18 years old who received otologic surgery at TJUH were included in this prospective observational study between November 2019 and August 2020. Patients were provided a survey for recording pain on postoperative days 0, 1, 3, and 7 and the amount of remaining opioids from their prescription. Opioid amounts were …

Postoperative Opioid-Prescribing Practices In Nasal Surgery: A Prospective Study, Brian M. Yan, S. Hamad Sagheer, Cory D. Bovenzi, Uche Nwagu, David Cognetti, Howard Krein, Ryan Heffelfinger

Phase 1

Introduction: Within facial plastic and reconstructive surgery (FPRS), prescription practices have trended toward prescribing larger amounts of perioperative opioids. However, there is limited literature regarding the postoperative pain experience and opioid consumption for FPRS. The purpose of our study was to investigate opioid prescription and consumption following procedures of the nose, with the aim of developing evidence-based guidelines for postoperative pain management.

Methods: In this prospective single center study, morphine milligram equivalents (MME) consumption and pain scores were collected in 72 patients who underwent nasal surgery. Patient demographics, MME use, and pain scores were examined. MME use was compared …