Digital Commons Network^™

Microbiota, Metabolic Profiles And Immune Biomarkers In Infants Receiving Formula With Added Bovine Milk Fat Globule Membrane: A Randomized, Controlled Trial, Chloe Christensen, Car Reen Kok, Cheryl L. Harris, Nancy Moore, Jennifer L. Wampler, Weihong Zhuang, Steven S. Wu, Robert Hutkins, Jacques Izard, Jennifer M. Auchtung

Journal Articles: Internal Medicine

INTRODUCTION: Few studies have evaluated the effects of milk fat globule membrane (MFGM) on microbiota and immune markers in early infant nutrition.

METHODS: In this double-blind randomized study, infants (7-18 days of age) received either bovine milk-based infant formula (Control) or similar formula with an added source (5 g/L) of bovine MFGM (INV-MFGM) for 60 days. A reference group received mother's own human milk over the same period (HM). Oral and stool samples were collected (Baseline and Day 60) to evaluate microbiota, immune markers, and metabolites.

RESULTS: At Day 60, stool bacterial diversity and richness were higher in formula groups …

From Biliary Dilatation To Meningitis: Finding Listeria In A Patient With Advanced Cholangiocarcinoma, Molly Jain Md, Mallika Gyawali Md, Sophia Lubrin Md

Internal Medicine Residency

This presentation won 1^st prize for the 2024 ACP Indiana conference in the oral clinical vignette. Case Presentation.

A Randomized Trial Of Vaginal Antiseptic Preparation Solutions To Reduce Bacteria Colony Counts In Patients Undergoing Vaginal Surgery, James R. Saelens, Adam J. Langer, Andrew N. Boeckley, Natalie M. Castillo, Julie A. Desouza, Jennifer L. Drerup, Kelly M. Muterspaw, Hannah M. Stump, Rose A. Maxwell, Geoffrey Towers

Obstetrics and Gynecology Faculty Publications

Antiseptic preparation of surgical sites is known to reduce the rate of infective complications. However, surgical site infections (SSI) remain a leading cause of post-operative hospitalizations, increasing patient stress and cost for the healthcare system.1-7 In gynecologic surgery, preparation of the vagina is performed to reduce bacterial load prior to surgery, though it is known to remain contaminated.3 In the US, only solutions containing povidone-iodine (PI) are FDA approved for vaginal preparation; though, a 2018 ACOG Practice Bulletin lists chlorhexidine gluconate (CHG) with low (<4%) alcohol concentrations as a reasonable option for off-label use.3 Other preparations for vaginal surgery have been reported including baby shampoo (BS) and a commercially available preparation, containing PCMX (para-chloro-meta-xylenol, Techni-care®, chloroxylenol), that is marketed specifically for use with mucous membranes.8-12 There is a growing need to establish evidence-based alternatives to iodine for vaginal preparation for patients with allergies or sensitivity to iodine-containing products while minimizing postoperative irritation. One retrospective study comparing BS to PI in gynecologic surgeries showed a non-significant lower rate of surgical site infection with BS.9 One major challenge for determining effectiveness of surgical scrubs for reducing SSI is the relatively rare occurrence of postoperative infection. As an alternative proxy for infection colony counts of bacteria/fungi, before and after preparation, have been used.12,13 BS has been shown to reduce bacterial loads in non-gynecologic surgery, but there is limited data regarding its use in vaginal surgery, even though surgeons have been using BS in cases of iodine allergy or intolerance to other antiseptics.9-12CHG use in vaginal surgery has been debated due to concerns about vaginal irritation, however studies have demonstrated that alteration of the solution to 2-4% chlorhexidine with low (4%) alcohol concentration was associated with mild to no vaginal irritation. CHG showed similar reduction in post-incision bacterial counts and wound infections in cesarean delivery, and reduced colony counts during hysterectomy (when compared to PI).14-20 PCMX and CHG were shown to significantly reduce bacterial colonization of extracted root canals, and PCMX has been marketed specifically for vaginal antiseptic preparation.21 While some information on the effectiveness of these four antiseptic preparations has been documented in the literature, at this time there are no randomized controlled trials comparing these solutions in the context of vaginal surgery. Further evaluation and research of antiseptic solutions is warranted to provide evidence for best practices in minimizing infection and irritation. The purpose of this study was to compare the effectiveness of three antiseptic solutions with the standard, PI, for reducing bacterial colonies as a proxy for SSI, and to assess postoperative irritation and infection symptoms.

Metabolism Shapes Immune Responses To Staphylococcus Aureus., Prabhakar Arumugam, Tammy Kielian

Journal Articles: Pathology and Microbiology

BACKGROUND: Staphylococcus aureus (S. aureus) is a common cause of hospital- and community-acquired infections that can result in various clinical manifestations ranging from mild to severe disease. The bacterium utilizes different combinations of virulence factors and biofilm formation to establish a successful infection, and the emergence of methicillin- and vancomycin-resistant strains introduces additional challenges for infection management and treatment.

SUMMARY: Metabolic programming of immune cells regulates the balance of energy requirements for activation and dictates pro- versus anti-inflammatory function. Recent investigations into metabolic adaptations of leukocytes and S. aureus during infection indicate that metabolic crosstalk plays a crucial role in …

Elucidating Granulocytic Myeloid-Derived Suppressor Cell Heterogeneity During Staphylococcus Aureus Biofilm Infection, Blake P. Bertrand, Cortney E. Heim, Scott A. Koepsell, Tammy Kielian

Journal Articles: Pathology and Microbiology

Myeloid-derived suppressor cells (MDSCs) are pathologically activated immature myeloid cells with immunosuppressive activity that expand during chronic inflammation, such as cancer and prosthetic joint infection (PJI). Myeloid-derived suppressor cells can be broadly separated into 2 populations based on surface marker expression and function: monocytic myeloid-derived suppressor cells (M-MDSCs) and granulocytic myeloid-derived suppressor cells (G-MDSCs). Granulocytic myeloid-derived suppressor cells are the most abundant leukocyte infiltrate during PJI; however, how this population is maintained in vivo and cellular heterogeneity is currently unknown. In this study, we identified a previously unknown population of Ly6G+Ly6C+F4/80+MHCII+ MDSCs during PJI that displayed immunosuppressive properties ex vivo. …

C1q Is Elevated During Chronic Staphylococcus Epidermidis Central Nervous System Catheter Infection, Matthew K. Beaver, Lara Bergdolt, Anna Dunaevsky, Tammy Kielian, Gwenn Skar

Journal Articles: Pathology and Microbiology

INTRODUCTION: Significant neurologic morbidity is caused by pediatric cerebrospinal fluid (CSF) shunt infections. The underlying mechanisms leading to impaired school performance and increased risk of seizures are unknown, however, a better understanding of these mechanisms may allow us to temper their consequences. Recent evidence has demonstrated important roles for complement proteins in neurodevelopment and neuroinflammation.

METHODS: We examined complement activation throughout

RESULTS: We found that MASP2 predominated early in catheter infection, but that Factor B was elevated at intermediate time points. Unexpectedly C1q was elevated at late timepoints when bacterial burdens were low or undetectable. Based on these findings and …

Antimicrobial Activity Of Gallium(Iii) Compounds: Pathogen-Dependent Targeting Of Multiple Iron/Heme-Dependent Biological Processes, Seoung-Ryoung Choi, Mohammed A. Hassan, Bradley E. Britigan, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

Metals play vital roles in biological systems, with iron/heme being essential for cellular and metabolic functions necessary for survival and/or virulence in many bacterial pathogens. Given the rise of bacterial resistance to current antibiotics, there is an urgent need for the development of non-toxic and novel antibiotics that do not contribute to resistance to other antibiotics. Gallium, which mimics iron, has emerged as a promising antimicrobial agent, offering a novel approach to combat bacterial infections. Gallium does not have any known functions in biological systems. Gallium exerts its effects primarily by replacing iron in redox enzymes, effectively inhibiting bacterial growth …

Aconitate Decarboxylase 1 Mediates The Acute Airway Inflammatory Response To Environmental Exposures, Aaron Schwab, Amy J. Nelson, Angela Gleason, Oliver Schanze, Todd A. Wyatt, Dhananjay Shinde, Peng Xiao, Vinai Chittezham Thomas, Chittibabu Guda, Kristina L. Bailey, Tammy Kielian, Geoffrey M. Thiele, Jill A. Poole

Journal Articles: Pathology and Microbiology

Background: Environmental lipopolysaccharide (LPS) and microbial component-enriched organic dusts cause significant lung disease. These environmental exposures induce the recruitment and activation of distinct lung monocyte/macrophage subpopulations involved in disease pathogenesis. Aconitate decarboxylase 1 (Acod1) was one of the most upregulated genes following LPS (vs. saline)exposure of murine whole lungs with transcriptomic profiling of sorted lung monocyte/macrophage subpopulations also highlighting its significance. Given monocyte/macrophage activation can be tightly linked to metabolism, the objective of these studies was to determine the role of the immunometabolic regulator ACOD1 inenvironmentalexposure-induced lung inflammation.

Methods: Wild-type (WT) mice were intratracheally (i.t.) instilled with 10 …

Bacterial Single-Cell Rna Sequencing Captures Biofilm Transcriptional Heterogeneity And Differential Responses To Immune Pressure, Lee E. Korshoj, Tammy Kielian

Journal Articles: Pathology and Microbiology

Biofilm formation is an important mechanism of survival and persistence for many bacterial pathogens. These multicellular communities contain subpopulations of cells that display metabolic and transcriptional diversity along with recalcitrance to antibiotics and host immune defenses. Here, we present an optimized bacterial single-cell RNA sequencing method, BaSSSh-seq, to study Staphylococcus aureus diversity during biofilm growth and transcriptional adaptations following immune cell exposure. BaSSSh-seq captures extensive transcriptional heterogeneity during biofilm compared to planktonic growth. We quantify and visualize transcriptional regulatory networks across heterogeneous biofilm subpopulations and identify gene sets that are associated with a trajectory from planktonic to biofilm growth. BaSSSh-seq …

Increasing The Efficacy Of Actinomycin D With Resveratrol In Aerodigestive Tract Cancers, Lukmon Morenikeji Raji

Theses, Dissertations and Capstones

Chemotherapy poses a significant challenge for cancer patients due to drug-associated toxicity, which often results from their effects on both healthy (normal) and cancerous cells. While various options aim to reduce toxicity and optimize beneficial effects, a comprehensive solution remains elusive. Cyclotherapy is one such approach developed to protect normal cells from the toxic effects of chemotherapy drugs. The basic principle underlying cyclotherapy is p53- dependent cell cycle arrest of normal cells while killing cancer cells via a p53-independent mechanism using a second drug. In our research, we investigated the inhibitory effects of a combination of two low-dose anticancer drugs, …

Management Considerations In A Case Of Sepsis Induced Takotsubo Cardiomyopathy In A Post-Operative Patient., Avraham Fox, Rachel Groening, Carsten Z. Steinmetz, Callaham A. Brock, Saptarshi Biswas

South Atlantic Division GME Research Day 2024

No abstract provided.

Dual Gallium Drug Treatment Against Carbapenem-Resistant Klebsiella Pneumoniae: Efficacy And Potential Mechanism(S) Of Action And Resistance, Zachary Scott, Seoung-Ryoung Choi, Bradley E. Britigan, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

Klebsiella pneumoniae (KLP) is a Gram-negative pathogen that can be highly antibiotic-resistant. Our group has worked with gallium-based compounds as a means of treating bacterial infections. Here the possible mechanism is investigated for dual therapy comprised of gallium nitrate (Ga(NO₃)₃) and gallium protoporphyrin (GaPP) on KLP. It is found that in vitro the combination of Ga(NO₃)₃ and GaPP is synergistic against KLP. The in vivo efficacy is of the dual therapy is additionally tested by treating pulmonary KLP infections in mice. Much greater effectiveness are observed in bacterial clearance and survival of mice …

Tetracycline And Oxacillin Act Synergistically On Biofilms And Display Increased Efficacy In Vivo Against Staphylococcus Aureus, Amy K. Tooke, Rebecca E. Hodges, Josie F. Pyrah, Kenneth W. Bayles, Stephen A. Renshaw, Simon J. Foster

Journal Articles: Pathology and Microbiology

Oxacillin (bactericidal) and tetracycline (bacteriostatic) are clinically relevant antibiotics that are routinely prescribed to treat Staphylococcus aureus infections but not conventionally used in combination. There is an urgent need for treatment regimens that can act upon biofilms during infection, associated with chronic infections on indwelling devices, as well as acute planktonic (systemic) infection. Here we show that in an in vitro model oxacillin and tetracycline act synergistically against S. aureus UAMS-1 biofilms, reducing the concentration of both antibiotics necessary to eradicate an established biofilm. Using an in vivo zebrafish larval infection model with S. aureus NewHG, they display improved bacterial …

How Does Plasma L-Fabp Level Correlate With Cardiovascular Disease Risk In Patients With Chronic Kidney Disease, And Can It Serve As A Reliable Biomarker For Risk Stratification?”, Nehad Refat Ibrahim, Ghadir Elsawy

Journal of Medicine in Scientific Research

Chronic kidney disease (CKD) affects up to 10% of the global adult population, with cardiovascular disease (CVD) being a major concern. CKD patients face increased CVD-related morbidity and mortality. While the exact mechanisms linking CKD and CVD are complex, traditional risk factors (e.g., diabetes, hypertension) and nontraditional factors (e.g., inflammation, oxidative stress) play a role. Liver-type fatty acid-binding protein (L-FABP) is associated with lipid metabolism and kidney injury. Few studies suggest L-FABP as a potential biomarker for CVD risk in CKD patients, but further research is needed to fully understand its role. This study aims to explore the link between …

Biotin For Hair Loss: Teasing Out The Evidence, Allyson Yelich, Hannah Jenkins, Sara Holt, Richard Miller

West Florida Division GME Research Day 2024

No abstract provided.

2-Methyl-2-Butanol (2m2b) Ingestion Related Toxicity, Elizabeth Diaz, Darshan B. Bhatty, Ngoc Vu, Sathish Karmegam

North Texas GME Research Forum 2024

2-methyl-2-butanol known as Tert-amyl alcohol (TAA) was previously used in the past for its hypnotic, anticonvulsant, and sedative properties.1 Both ethanol and 2M2B stimulate GABA-A receptors causing similar CNS effects.1 Animal studies have shown that toxicity is greater than 2-pentanol, 3-methyl-1-butanol, and ethanol1. 2M2B is replacing ethanol due to its low cost per dose, high potency, and does not produce a hangover as it is not metabolized to aldehydes.1 This case report describes the clinical course of a patient after intoxication with 2M2B and bringing awareness as it is difficult to confirm diagnosis since there are no specific clinical features …

Multidisciplinary Simulation-Based Trauma Education For General Surgery Interns, Jennifer Austin, April Miller, Jeremiah Avarana, Alicia Lay

North Texas GME Research Forum 2024

Introduction: According to the American Society of Gastroenterology Endoscopy (ASGE), choledocholithiasis is defined as the presence of gallstones in biliary tree. Choledocholithiasis is concomitantly present in approximately 1 to 10 percent of patients with cholelithiasis. Choledocholithiasis can be described as small <15 >mm, large >15 mm, and difficult due to anatomic location, impaction, or unusual hardness/ shape. Choledocholithiasis is managed endoscopically with large balloon papillary dilation, cholangioscopy-guided intraductal laser and electrohydraulic lithotripsy (EHL), and escalation to laparoscopic common bile duct exploration, if endoscopic procedures fail. Thus far, there are sparse studies that show the requirement of choledochotomy in large and …

Cancer Care Annual Report 2022-2023, Children's Mercy Kansas City

Cancer Center Annual Reports

Annual report of cancer care and oncology services at the Children's Mercy Kansas City, a pediatric medical center. This year’s report focuses on Brain Tumors.

Mechanosensory Encoding In Ex Vivo Muscle–Nerve Preparations, Stephen N. Housley, Evelyn A. Gardolinski, Paul Nardelli, J'Ana Reed, Mark M. Rich, Timothy C. Cope

Neuroscience, Cell Biology & Physiology Faculty Publications

Our objective was to evaluate an ex vivo muscle-nerve preparation used to study mechanosensory signalling by low threshold mechanosensory receptors (LTMRs). Specifically, we aimed to assess how well the ex vivo preparation represents in vivo firing behaviours of the three major LTMR subtypes of muscle primary sensory afferents, namely type Ia and II muscle spindle (MS) afferents and type Ib tendon organ afferents. Using published procedures for ex vivo study of LTMRs in mouse hindlimb muscles, we replicated earlier reports on afferent firing in response to conventional stretch paradigms applied to non-contracting, that is passive, muscle. Relative to in vivo …

Targeting Transitioning Lung Monocytes/Macrophages As Treatment Strategies In Lung Disease Related To Environmental Exposures, Aaron Schwab, Todd A. Wyatt, Grace Moravec, Geoffrey M. Thiele, Amy J. Nelson, Angela Gleason, Oliver Schanze, Michael J. Duryee, Debra J. Romberger, Ted R. Mikuls, Jill A. Poole

Journal Articles: Pulmonary & Critical Care Med

Background: Environmental/occupational exposures cause significant lung diseases. Agricultural organic dust extracts (ODE) and bacterial component lipopolysaccharide (LPS) induce recruited,transitioning murine lung monocytes/macrophages, yet their cellular role remains unclear.

Methods: CCR2 RFP⁺ mice were intratracheally instilled with high concentration ODE (25%), LPS (10 μg), or gram-positive peptidoglycan (PGN, 100 μg) for monocyte/macrophage cell-trafficking studies. CCR2 knockout (KO) mice and administration of intravenous clodronate liposomes strategies were employed to reduce circulating monocytes available for lung recruitment following LPS exposure.Lung tissues and bronchoalveolar lavage fluid (BALF) were collected. Pro-inflammatory and/or pro-fibrotic cytokines, chemokines, and lung extracellular matrix mediators were quantitated by ELISA. …

Recurrent Non-Sustained Ventricular Tachycardias In A Patient With Suspicion Of Transthyretin Amyloid Cardiomyopathy: A Case Report, Chinar Singh, Meng Xie, Poonam Choudhry, Asif Jawaid

East Florida Division GME Research Day 2024

Objective: This case study aims to highlight the mechanisms, clinical presentation, diagnostic strategies, and management approach utilized for recurrent non-sustained ventricular tachycardias in a patient with suspected cardiac amyloidosis.

Background: Amyloidosis is a group of disorders characterized by the abnormal deposition of amyloid proteins in tissues and organs throughout the body. These proteins aggregate into insoluble fibrils that disrupt normal cellular function, leading to a range of clinical manifestations depending on the affected organs. Cardiac amyloidosis is characterized by the deposition of amyloid fibrils specifically in the myocardial tissue, leading to restrictive cardiomyopathy, progressive heart failure and arrhythmias. Ventricular tachycardia …

Exploring Angiotensin Ii And Oxidative Stress In Radiation-Induced Cataract Formation: Potential For Therapeutic Intervention, Vidya P. Kumar, Yali Kong, Riana Dolland, Sandra R. Brown, Kan Wang, Damian Dolland, David Mu, Milton L. Brown

Department of Biomedical and Translational Sciences Faculty Publications

Radiation-induced cataracts (RICs) represent a significant public health challenge, particularly impacting individuals exposed to ionizing radiation (IR) through medical treatments, occupational settings, and environmental factors. Effective therapeutic strategies require a deep understanding of the mechanisms underlying RIC formation (RICF). This study investigates the roles of angiotensin II (Ang II) and oxidative stress in RIC development, with a focus on their combined effects on lens transparency and cellular function. Key mechanisms include the generation of reactive oxygen species (ROS) and oxidative damage to lens proteins and lipids, as well as the impact of Ang II on inflammatory responses and cellular apoptosis. …

Evaluating The Efficacy Of The Archaeal Proteasome To Alleviate Protein-Misfolding Retinopathy, Celine Brooks

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nearly all neurodegenerative diseases (NDs) and some eye diseases are characterized by the presence of misfolded and aggregated proteins. The ubiquitin proteasome system (UPS) is responsible for degrading the majority of proteins including misfolded and aggregated proteins. However, in NDs the performance of the UPS is impaired, and this impairment partially comes from these protein aggregates inhibiting the proteasome. This inhibition leads to an accumulation of protein aggregates, more proteasomal inhibition, and fewer chaperones for newly synthesized proteins, triggering a collapse in proteostasis, which is thought to contribute to the pathogenesis of NDs. Consequently, stimulating proteasome function is being investigated …

Lung-Delivered Il-10 Therapy Elicits Beneficial Effects Via Immune Modulation In Organic Dust Exposure-Induced Lung Inflammation, Aaron D. Schwab, Todd A. Wyatt, Amy J. Nelson, Angela Gleason, Rohit Gaurav, Debra J. Romberger, Jill A. Poole

Journal Articles: Pulmonary & Critical Care Med

Efficacious therapeutic options capable of resolving inflammatory lung disease associated with environmental and occupational exposures are lacking. This study sought to determine the preclinical therapeutic potential of lung-delivered recombinant interleukin (IL)-10 therapy following acute organic dust exposure in mice. Here, C57BL/6J mice were intratracheally instilled with swine confinement organic dust extract (ODE) (12.5%, 25%, 50% concentrations) with IL-10 (1 μg) treatment or vehicle control intratracheally-administered three times: 5 hr post-exposure and then daily for 2 days. The results showed that IL-10 treatment reduced ODE (25%)-induced weight loss by 66% and 46% at Day 1 and Day 2 post-exposure, respectively. IL-10 …

Single-Cell Profiling Reveals A Conserved Role For Hypoxia-Inducible Factor Signaling During Human Craniotomy Infection, Zachary Van Roy, Gunjan Kak, Lee E. Korshoj, Joseph P. Menousek, Cortney E. Heim, Rachel W. Fallet, James Campbell, Carol Reynolds Geary, Bo Liu, Santhi Gorantla, Larisa Y Poluektova, Bin Duan, Walter S. Campbell, William Thorell, Tammy Kielian

Journal Articles: Pathology and Microbiology

Neurosurgeries complicated by infection are associated with prolonged treatment and significant morbidity. Craniotomy is a common neurosurgical procedure; however, the cellular and molecular signatures associated with craniotomy infection in human subjects are unknown. A retrospective study of over 2,500 craniotomies reveals diverse patient demographics, pathogen identity, and surgical landscapes associated with infection. Leukocyte profiling in patient tissues from craniotomy infection characterizes a predominance of granulocytic myeloid-derived suppressor cells that may arise from transmigrated blood neutrophils, based on single-cell RNA sequencing (scRNA-seq) trajectory analysis. Single-cell transcriptomic analysis identifies metabolic shifts in tissue leukocytes, including a conserved hypoxia-inducible factor (HIF) signature. The …

Natural Killer Cell Effector Function Is Critical For Host Defense Against Alcohol-Associated Bacterial Pneumonia, Daniel Villageliu, Kelly C. Cunningham, Deandra R. Smith, Daren L. Knoell, Mason Mandolfo, Todd A. Wyatt, Derrick R. Samuelson

Journal Articles: Internal Medicine

Alcohol use is an independent risk factor for the development of bacterial pneumonia due, in part, to impaired mucus-facilitated clearance, macrophage phagocytosis, and recruitment of neutrophils. Alcohol consumption is also known to reduce peripheral natural killer (NK) cell numbers and compromise NK cell cytolytic activity, especially NK cells with a mature phenotype. However, the role of innate lymphocytes, such as NK cells during host defense against alcohol-associated bacterial pneumonia is essentially unknown. We have previously shown that indole supplementation mitigates increases in pulmonary bacterial burden and improves pulmonary NK cell recruitment in alcohol-fed mice, which were dependent on aryl hydrocarbon …

A Pediatric Patient With Severe Malaria Successfully Treated With Artesunate, Aoife Schanche, Annabel Ward, Ricardo Zegarra-Linares

South Atlantic Division GME Research Day 2024

No abstract provided.

The Protective And Pathological Role Of The Spleen In Malaria, Julie Hwang, Md, Amy Dechet

Books, Presentations, Posters, Etc.

Case Presentation: • Background: There were 241 million cases of malaria globally. Compared to 2,000 cases in the U.S. Splenomegaly has previously been used to determine the severity of malaria. This is a rare case of hyper reactive malarial splenomegaly (HMS) due to chronic plasmodium ovale • 23 year-old female with gradually worsening left upper quadrant abdominal pain of 1 month. Pain sharp and stabbing in quality, no alleviating or aggravating factors. Associated with subjective early satiety and 10 Ibs weight loss, generalized weakness, shortness of breath • PMH: Schistosomiasis 2008,unclear if treated • Soc: Born in Congo and immigrated …

Glioblastoma Standard Of Care: Effects On Tumor Evolution And Reverse Translation In Preclinical Models, Louis Rodgers, John L. Villano, Anika M. S. Hartz, Björn Bauer

UK CARES Faculty Publications

Glioblastoma (GBM) presents a significant public health challenge as the deadliest and most common malignant brain tumor in adults. Despite standard-of-care treatment, which includes surgery, radiation, and chemotherapy, mortality rates are high, underscoring the critical need for advancing GBM therapy. Over the past two decades, numerous clinical trials have been performed, yet only a small fraction demonstrated a benefit, raising concerns about the predictability of current preclinical models. Traditionally, preclinical studies utilize treatment-naïve tumors, failing to model the clinical scenario where patients undergo standard-of-care treatment prior to recurrence. Recurrent GBM generally exhibits distinct molecular alterations influenced by treatment selection pressures. …

Clinical Trial Protocol For Beach: A Phase 2a Study Of Mw189 In Patients With Acute Nontraumatic Intracerebral Hemorrhage, Radhika Avadhani, Wendy C. Ziai, Richard E. Thompson, W. Andrew Mould, Karen Lane, Angeline Nanni, Michael Lacobelli, Matthew F. Sharrock, Lauren H. Sansing, Linda J. Van Eldik, Daniel F. Hanley

Neurology Faculty Publications

Patients with acute spontaneous intracerebral hemorrhage (ICH) develop secondary neuroinflammation and cerebral edema that can further damage the brain and lead to increased risk of neurologic complications. Preclinical studies in animal models of acute brain injury have shown that a novel small-molecule drug candidate, MW01-6-189WH (MW189), decreases neuroinflammation and cerebral edema and improves functional outcomes. MW189 was also safe and well tolerated in phase 1 studies in healthy adults. The proof-of-concept phase 2a Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) clinical trial is a first-in-patient, multicenter, randomized, double-blind, placebo-controlled trial. It is designed to determine the safety and tolerability …