Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons^™

Development, Validation, And Diagnostic Performance Of A Novel Radiomic Model For Predicting Prostate Cancer Recurrence, Linda M. Huynh

Theses & Dissertations

Multi-parametric magnetic resonance imaging (MP-MRI)-derived radiomics have been shown to capture sub-visual patterns for the quantitative characterization of prostate cancer (PC) phenotypes. The present dissertation seeks to develop, evaluate, and compare the performance of an MRI-derived radiomic model for the prediction of PC recurrence following definitive treatment with radical prostatectomy (RP).

MP-MRI was obtained from 339 patients who had a minimum of 2 years follow-up following RP at three institutions. The prostate was manually delineated as the region of interest and 924 radiomic features were extracted. All features were evaluated for stability via intraclass correlation coefficient (ICC) and image normalization …

Leukocyte Subsets In The Peripheral Blood And Spleen Of Gastrointestinal Cancer Patients, Kathryn E. Cole

Theses & Dissertations

In 2022, an estimated 62,210 people will be diagnosed with pancreatic ductal adenocarcinoma (PDAC) and approximately 49,830 will die from the disease. Current treatment strategies for gastrointestinal (GI) cancer patients, such as PDAC, have shown limited benefit, suggesting the need to develop novel, multimodality therapeutic approaches. Adoptive cellular therapy (ACT) using autologous tumor infiltrating lymphocytes (TILs) has shown efficacy in patients with melanoma; however, this approach is costly and requires extensive cell culture for sufficient numbers of T-cells for infusion. GI cancer patients with borderline resectable disease, whose primary tumor is adjacent to the splenic vasculature, can sometimes undergo a …

Proof Of Concept: The Use Of Renal Biomarkers In Critically Ill Pediatric Patients For Therapeutic Drug Monitoring, Christopher Lee Shaffer

Theses & Dissertations

Acute kidney injury (AKI) is a serious and common complication in critically ill pediatric patients. The incidence of pediatric AKI continues to increase, especially in patients who undergo surgical correction of congenital heart defects. Serum creatinine and urine output are the most commonly used tools to assess renal function, with international guidelines standardizing AKI-definitions based upon these parameters. However, changes in serum creatinine can occur 24 hours or later after a renal insult event, delaying the diagnosis and potential interventions to reverse injury. It is critical to identify endogenous renal biomarkers within the pediatric population that are both timely and …

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

Biomedical Porcine Models For The Study Of Surgical Hemostasis, Hindlimb Ischemia, And Pancreatic Cancer, Shruthishree Aravind

Theses & Dissertations

Murine models have dominated the world of biomedical research and comparative medicine since their development in the early 1900s. [1] While they may be suitable models to study proteomics and genomics, they may not serve as effective translational models. [2-4] Murine models do not accurately model the pathophysiology of human disease and are limited by their size, application of medical imaging and intervention, which reduces their overall preclinical predictive value. [2-4]

Porcine models on the other hand, are slowly and steadily bridging the gap between murine models and human patients. [5] Pigs …

Effects Of Acute Intracranial Pressure Changes On Optic Nerve Head Morphology In Humnans And Pig Model, Sachin Kedar

Theses & Dissertations

The optic nerve head (ONH) is located at the interface of intracranial and intraocular compartments. It is comprised of lamina cribrosa (LC), a fenestrated connective tissue tethered to the posterior sclera across the scleral canal. Since LC is exposed to intraocular pressure (IOP) anteriorly and intracranial pressure (ICP) posteriorly, it is an ideal site for noninvasively detecting intracranial pressure (ICP) fluctuation. We hypothesized that the pressure differential between IOP and ICP across LC, will determine LC position and meridional diameter of scleral canal (also called Bruch’s membrane opening- BMOD). We tested our hypothesis in 19 human subjects undergoing medically necessary …

Novel Detection And Treatment Strategies For Pancreatic Ductal Adenocarcinoma, Joseph Carmicheal

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with an estimated 5-year survival rate of less than 9%. The high lethality of PDAC is due to two primary reasons: the discovery of PDAC at later stages, with locally invasive or metastatic disease present at the time of initial diagnosis as well as the lack of efficacious therapeutic interventions that significantly impact survival. In this dissertation, we sought to discover and test novel detection and treatment strategies for PDAC. Firstly, serum EVs were investigated as potential non-invasive liquid biopsy biomarkers, to serve as a means of early cancer …

Immersive Virtual Reality Training Improved Upper Extremity Function In Patients With Spinal Cord Injuries: A Case Series, Anqi Zhang

Theses & Dissertations

Virtual reality (VR) is an emerging treatment tool to engage people in environments that appear and feel similar to real-world objects and events.¹ There are various levels of evidence that VR can potentially promote functional activity and neuroplasticity in patients with neurological disorders like spinal cord injury (SCI).^2,3

In this case series, we explored the feasibility of using commercially available immersive VR technology as an augmented treatment in the SCI population and compare participant’s suitability for this intervention. Three male SCI participants were recruited in a subacute inpatient rehabilitation facility and participated in VR intervention twice a week …

Synthesis And Characterization Of Long Acting Darunavir Prodrugs, Mary Banoub

Theses & Dissertations

Patient adherence is critical for ART success to ensure adequate viral suppression, therefore, long-acting antiretrovirals are soon replacing current daily regimens. In recent years, two drugs were successfully transformed into long-acting injectables; CAB LA and RPV LA. These long-acting nanoformulations made it possible to abandon the daily pill burden, instead approximately a bimonthly injection of both drugs is enough to suppress and maintain viral load suppression. Our laboratory has been instrumental in transforming FDA-approved and experimental-HIV medications into long-acting slow effective release drugs, also known as LASER ART. LASER ART consists of slow drug metabolism and high permeability and retention …

Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann

Theses & Dissertations

RATIONALE: Our laboratories birthed the field of human immunodeficiency virus (HIV) theranostics. The new field allows simultaneous detection (diagnostics) and treatment (therapeutic) for the identification, treatment and inevitable elimination of virus in cell and tissue compartments. By employing theranostics, antiretroviral drugs (ARVs) can be tracked in lymph nodes, gut, spleen and liver. Cellular viral reservoirs including CD4+ T cell populations and mononuclear phagocytes (MP; monocytes, macrophages, microglia and dendritic cells) along with subcellular endosomal structures can now be targeted for drug delivery bringing therapeutics to areas where virus replicates. The overarching idea rests in improving precision targeted ARV delivery. …

Evaluation Of The Role Of Microvascular Pathology On Peripheral Artery Disease, Constance Mietus

Theses & Dissertations

Background: Peripheral Artery Disease (PAD) begins with atherosclerotic narrowing of arteries, including those that supply the legs. Individuals with PAD experience pain during walking, which becomes increasingly limiting. Studies from our group and others have shown that a myopathy is present in the skeletal muscle of PAD patients, and is characterized by myofiber degeneration, fibrosis, and remodeling of vessels ranging from 50 – 150 mm in diameter. However, microvascular pathology, particularly of the smallest microvessels (5 – 15 mm in diameter) remains poorly characterized. Furthermore, little is known about the relationships between microvascular architecture, microperfusion, and patient walking performance. We …

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

A Study Of Acoustically Activated Nanodroplets, Songita Choudhury

Theses & Dissertations

Current treatment of acute myocardial infarction (AMI), which is the main pathophysiological event leading to death in the United States, has advanced considerably with the introduction of emergent percutaneous interventions, but there remains an urgent need for novel techniques to rapidly and accurately detect infarcted or ischemic tissue that results from AMI. Ultrasound contrast agents, also known as microbubbles (MB), have become commonplace in echocardiography. However, MBs are purely intravascular tracers and unable to cross endothelial barriers due to size. The limitations of MBs, namely size and short circulation times within the human body, led to the development of phase-change …

Cervical Spine Angles, Craniocervical Posture, Neck Length, And Oropharyngeal Airway Analyses Of Sleep Apnea Patients In Both Supine And Upright Positions: A Retrospective 3-D Imaging Study, Brian Tuan Luong

Theses & Dissertations

Obstructive sleep apnea (OSA) is one of the most common respiratory disorders. Previous airway studies of OSA subjects have largely relied on 2-D radiographs.

The purpose of this study is to use 3-D imaging to the analyze the relationships among cervical spine angles, craniocervical posture, cervical spine length and the oropharyngeal airway volume in OSA patients in both the supine and upright positions.

Twenty-eight OSA subjects with 3-D imaging were included. Airway, craniocervical posture, spine angles, and spine length were assessed using Dolphin 11.8. Correlation analyses were utilized to detect associations among the recorded and measured variables. Mean differences were …

Long-Acting Antiretroviral Nanoformulation Development And Subcellular Trafficking, Dongwei Guo

Theses & Dissertations

The introduction of nanoformulated antiretroviral therapeutic regimens is a promising alternative to standard once a day oral treatment of HIV infection. Our lab has pioneered this effort and was successful in harnessing mononuclear phagocytes (monocytes, dendritic cells and macrophages) as nanoformulated drug carriers. The approach was developed as Trojan horses for drug transport, delivery and distribution to sites of viral replication in order to facilitate microbial elimination in HIV sanctuaries. However, the remaining challenges for current antiretroviral nanoformulations include to formulate a broad range of hydrophilic short-acting drugs, and to elucidate the mechanism of sequestered nanoparticles in macrophages at the …

The Effect Of A Preanaesthesia Clinic Consultation On Adult Patient Anxiety In Aga Khan University Hospital; A Cohort Study, Anthony Kamau

Theses & Dissertations

Background: Preoperative anxiety is a common perioperative complication, according to studies done it is seen in approximately 11-80% of adults undergoing surgery. Various pharmacological and non pharmacological techniques have been used to reduce preop anxiety.

One of the goals of the preanaesthesia clinic is to allay anxiety. Literature shows that a preanaesthesia clinic evaluation reduces anxiety however b current studies done on anxiety and the preanaesthesia clinic have not quantified this reduction.

Objective: To determine the reduction in anxiety in patients evaluated in the clinic versus those evaluated in the ward.

Study Design: A cohort and before – after study …

A Randomized Control Trial Comparing Weight Adjusted Dose Versus Fixed Dose Prophylactic Phenylephrine Infusion On Maintaining Systolic Blood Pressure During Caeserean Section Under Spinal Anaesthesia, Lucy Wambui Mwaura

Theses & Dissertations

Background: Spinal anaesthesia is the standard of care for elective caesarean delivery. Its advantages over general anaesthesia include: decreased blood loss, reduced postoperative pain and faster recovery time. Despite these advantages, the sympathetic blockade induced by spinal anaesthesia results in 80 percent incidence of hypotension without prophylactic management. This hypotension can cause: nausea, vomiting, cardiovascular collapse or even loss of consciousness in the mother, and fetal acidosis.

Current evidence supports co-loading with intravenous fluids in conjunction with the use of vasopressors as the most effective way to prevent and treat the hypotension. Phenylephrine is the accepted vasopressor of choice in …