Medical Specialties Commons^™

Interventions To Prevent And Manage Infections In Pregnancy, Rahima Yasin, Li Jiang, Jai K. Das, Zulfiqar Ahmed Bhutta

Institute for Global Health and Development

Background: Care interventions aimed at preventing and treating maternal infections during the gestational period are of paramount importance. Timely immunizations, screening strategies, and management of maternal infections reduce the risk of complications for the developing fetus and play a pivotal role in improving neonatal outcomes.
Summary: We aim to summarize evidence for a total of thirteen interventions, pertaining to the prevention and treatment of maternal infections during the antenatal period, from Every Newborn Series published in The Lancet 2014. We identified the most recent systematic reviews, extracted data from each review, and conducted a sub-group meta-analysis for low-income countries and …

Hispanic Patients Undergoing Spinal Fusion For Neuromuscular Scoliosis Sustain Health Inequalities, Armando S Martinez, David Momtaz, Travis Kotzur, Alexandra Mclennan, Abdullah Ghali, Farhan Ahmad, Ebubechi Adindu, Alan C Santiago-Rodriquez, Ali Seifi, Brian Smith

Faculty, Staff and Students Publications

INTRODUCTION: Pre- and postoperative optimization remains a complex process impacted by various demographic factors. Our study aims to identify and describe those demographic factors associated with poor outcomes after spinal fusion with instrumentation in neuromuscular scoliosis to reduce health disparities and improve postoperative outcomes.

METHODS: A retrospective analysis was conducted using Healthcare Cost and Utilization Project data from 2016 to 2020, encompassing a random sample of 20% of procedures in the United States. Data included demographic and hospital variables, including days from admission to the procedure, length of stay, recovery time, total charge, discharge disposition, and mortality rates. In addition …

Pulmonary Pathology In Culture-Negative Sepsis: A Potential Confounder For Sepsis Treatment And Research, Brett Biebelberg

SKMC Student Presentations and Publications

No abstract provided.

Use Of Multi-Modal Non-Contrast Mri To Predict Functional Outcomes After Stroke: A Study Using Dp-Pcasl, Dti, Noddi, And Map Mri, Julia Diamandi, Christian Raimondo, Keenan Piper, Joanna Roy, Stephanie Serva, Mahdi Alizadeh, Adam Flanders, Stavropoula Tjoumakaris, Michael Gooch, Pascal Jabbour, Robert Rosenwasswer, Nikolaos Mouchtouris

Department of Neurosurgery Faculty Papers

PURPOSE: This study aims to assess whether water exchange rate (k_w), a surrogate for blood-brain barrier (BBB) permeability, is associated with functional outcomes in patients with acute ischemic stroke (AIS).

METHODS: We studied 22 AIS patients enrolled from 1/2022 to 4/2024 who underwent multi-modal non-contrast imaging on a 3.0-Tesla scanner, including DP-pCASL, DTI, NODDI and MAP imaging. For each parametric map, the intensity and standard deviation (SD) were calculated for the infarcted region. The diffusion maps included were b0, Fractional Anisotropy (FA), Mean Diffusivity (MD), Intra-cellular Volume Fraction (ICVF), Free Water Fraction (FWF), and Orientation Dispersion Index (ODI), …

Prevalence Of Autoimmune Diseases In Patients Treated With Immune Checkpoint Inhibitors: An Epidemiological Study Using A Global Network Of Health Care Organizations, Pushti Khandwala, Devashish Desai, Arthur Lau

Einstein Health Papers

OBJECTIVE: Evaluate prevalence of new onset autoimmune conditions (ACs) after commencement of immune checkpoint inhibitors (ICIs).

METHODS: This retrospective observational study was done using TriNetX. Patients with neoplasm for which ICIs were approved were stratified into two groups based on ICI use. Multivariate Cox proportional hazard models and Kaplan Meier method were used to assess risk of developing ACs among the groups. Subgroup analysis was done to evaluate risk of ACs in patients receiving cytotoxic T-lymphocyte-associated protein 4 inhibitor (CTLA4i) versus program cell death protein 1 inhibitor (PD1i) and program death ligand 1 inhibitor (PDL1i) inhibitors and combination treatment (CT) …

Ethnic Disparities In Hba1c And Hypoglycemia Among Youth With Type 1 Diabetes: Beyond Access To Technology, Social Deprivation And Mean Blood Glucose, J. Pemberton, Zhide Fang, Stuart Chalew, S. Uday

School of Public Health Faculty Publications

Introduction The UK national pediatric diabetes audit reports higher HbA1c for children and young people (CYP) with type 1 diabetes (T1D) of Black ethnicity compared with White counterparts. This is presumably related to higher mean blood glucose (MBG) due to lower socioeconomic status (SES) and less access to technology. We aimed to determine if HbA1c ethnic disparity persists after accounting for the above variables. Research design and methods A retrospective analysis of participants who received structured education in continuous glucose monitoring (CGM) use was conducted at a tertiary center. HbA1c was paired with glucose metrics from 90-day CGM data. The …

A Randomized, Placebo-Controlled, Cross-Over Trial Of Ketamine In Rett Syndrome, Kathleen Campbell, Jeffrey L Neul, David N Lieberman, Elizabeth Berry-Kravis, Tim A Benke, Cary Fu, Alan Percy, Bernhard Suter, David Morris, Randall L Carpenter, Eric D Marsh, Jana Von Hehn

Faculty, Staff and Students Publications

BACKGROUND: Preclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy.

DESIGN: This was a sequentially initiated, dose-escalating cohort, placebo-controlled, double blind, randomized sequence, cross-over study of oral ketamine in 6-12-year-old girls with RTT to evaluate short-term safety and tolerability and explore efficacy.

METHODS: Participants were randomized to either five days treatment with oral ketamine or matched placebo, followed by a nine-day wash-out period and then crossed-over to the opposite …

Atm Expression And Activation In Ataxia Telangiectasia Patients With And Without Class Switch Recombination Defects, Fereshte Salami, Tannaz Moeini Shad, Nazanin Fathi, Hanieh Mojtahedi, Marzie Esmaeili, Sepideh Shahkarami, Ladan Gol Mohammad Pour Afrakoti, Parisa Amirifar, Samaneh Delavari, Hassan Nosrati, Azadehsadat Razavi, Mohammad Reza Ranjouri, Mahsa Yousefpour, Zahra Hamidi Esfahani, Gholamreza Azizi, Mahmoudreza Ashrafi, Nima Rezaei, Reza Yazdani, Hassan Abolhassani

Department of Neurology Faculty Papers

BACKGROUND: Ataxia telangiectasia mutated (ATM) kinase plays a critical role in DNA double-strand break (DSB) repair. Ataxia telangiectasia (A-T) patients exhibit abnormalities in immunoglobulin isotype expression and class switch recombination (CSR). This study investigates the role of residual ATM kinase expression and activity in the severity of A-T disease.

METHODS: A-T patients with defined genetic diagnoses were classified based on CSR and based on the severity of their medical complications. Isolated peripheral blood mononuclear cells from any patient were evaluated before and after exposure to 0.5 Gy ionizing radiation for one minute. Western blotting was performed to identify the expression …

Case Report On Endocrine Induced Paralysis - " Unraveling The Impact Of Thyrotoxicosis On Potassium Homeostasis.", Srujith Pullipudi, Basava Chethan, Srinath K. M, Savitha Vijayakumar, Meghna B.S.

Digital Journal of Clinical Medicine

Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism, marked by episodes of muscle weakness and hypokalaemia. Although it predominantly affects young Asian men, it can also occur in females and individuals from non-Asian ethnic groups. TPP is a treatable form of hypokalaemic periodic paralysis and can often be the first indication of thyrotoxicosis. Triggers such as a high-carbohydrate diet, strenuous exercise, emotional stress, and steroid use can provoke TPP attacks. During an acute episode, the key diagnostic indicators are hypokalaemia along with elevated levels of thyroxine (T4) and triiodothyronine (T3). Treatment consists of two phases: promptly correcting hypokalaemia …

Comparative Outcomes Of Endovascular Vs. Surgical Treatment In Craniocervical Junction Dural Arteriovenous Fistulas: A Systematic Review And Meta-Analysis, Basel Musmar, Joanna Roy, Atakan Orscelik, Sravanthi Koduri, Spyridon Karadimas, Saman Sizdahkhani, Elias Atallah, Stavropoula Tjoumakaris, Michael Gooch, Hekmat Zarzour, Ritam Ghosh, Richard Schmidt, Robert Rosenwasser, Pascal Jabbour

Department of Neurosurgery Faculty Papers

BACKGROUND: Craniocervical junction dural arteriovenous fistulas (CCJ-DAVFs) are rare and complex vascular malformations that are challenging to diagnose and treat. This study aims to compare surgical and endovascular treatments for CCJ-DAVFs through a systematic review and meta-analysis.

METHODS: A systematic review and meta-analysis was conducted according to the PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched from inception to July 2024.

RESULTS: Fifteen studies involving 266 patients were included. Of these, 143 (53.8 %) patients underwent surgical treatment alone and 123 (46.2 %) underwent endovascular treatment alone. In the surgical group, the complete obliteration rate at last …

Superotemporal Predisposition To Traumatic Subretinal Fibrosis In Stargardt Disease: A Case Report, Jaime Nassur, Jose Pulido, Jose Pulido, Alaa Ghoneim, Anton Orlin, Richard Kaiser, Saif Hamdan

Wills Eye Hospital Papers

PURPOSE: Subretinal fibrosis has been reported as a presumed late sequela of orbital trauma in those with Stargardt disease (STGD). This case report highlights the sequential pathologic changes in response to trauma utilizing multimodal imaging.

OBSERVATIONS: An asymptomatic 19-year-old female with no significant ocular history presented for possible drusen. Initial imaging noted yellow-white pisciform perifoveal flecks in both eyes with corresponding hyper-and hypo-fluorescent lesions on fundus autofluorescence and hyperreflective deposits on near-infrared and spectral-domain optical coherence tomography (SD-OCT). A few months later, the patient presented with a new onset "black shadow" in the right eye after a traumatic periorbital injury, …

Management And Outcome Of Invasive Clindamycin-Resistant Mrsa Community-Associated Infections In Children, Amanda E Macias, Grant Stimes, Sheldon L Kaplan, Jesus G Vallejo, Kristina G Hulten, J Chase Mcneil

Faculty, Staff and Students Publications

Background: Clindamycin resistance among community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) complicates the management of a challenging infection. Little data exist to guide clinicians in the management of invasive clindamycin-resistant CA-MRSA infections in children and studies using oral regimens such as trimethoprim-sulfamethoxazole (TMP-SMX) and linezolid for treatment of these infections are limited. We sought to reevaluate antibiotic management among invasive CA-MRSA at a tertiary children’s hospital.

Methods: Cases of invasive clindamycin-resistant MRSA infections in children were identified through an ongoing S. aureus surveillance study. Eligible cases were those occurring in otherwise healthy children from 2011–2021. Medical records were reviewed.

Results: Thirty-four subjects …

Congenital Rickets, Melissa Intriago

Mako: NSU Undergraduate Student Journal

No abstract provided.

Il-1Β In Neoplastic Disease And The Role Of Its Tumor-Derived Form In The Progression And Treatment Of Metastatic Prostate Cancer, Yetunde Oyende, Luke Taus, Alessandro Fatatis

Kimmel Cancer Center Faculty Papers

Since its discovery, IL-1β has taken center stage as a key mediator of a very broad spectrum of diseases revolving around immuno-mediated and inflammatory events. Predictably, the pleiotropic nature of this cytokine in human pathology has led to the development of targeted therapeutics with multiple treatment indications in the clinic. Following the accumulated findings of IL-1β's central modulatory role in the immune system and the implication of inflammatory pathways in cancer, the use of IL-1β antagonists was first proposed and then also pursued for oncology disorders. However, this approach has consistently relied on the perceived need of interfering with IL-1β …

Atrial Fibrillation Recurrence Risk After Catheter Ablation In Patients With Rheumatoid Arthritis: A Systematic Review And Meta-Analysis, Pongprueth Rujirachun, Phuuwadith Wattanachayakul, Svita Taveeamornrat, Patompong Ungprasert, Nithi Tokavanich, Krit Jongnarangsin

Einstein Health Papers

BACKGROUND: The association between rheumatoid arthritis (RA) and the risk of developing atrial fibrillation (AF) is well-established. However, data on the impact of RA on AF recurrence postcatheter ablation (CA) remain unclear. This current study aimed to assess the impact of RA on AF recurrence after catheter-based pulmonary vein isolation.

METHODS: Potentially eligible studies were identified from Medline and EMBASE databases from inception to December 20, 2023. Eligible study must consist of two cohorts of patients with and without RA who underwent catheter ablation for AF. Pooled risk ratio (RR) and 95% CI were calculated using Dersimonian and Laird's random-effect, …

Expansion Of Genotypic And Phenotypic Findings In Adamts18-Related Ocular Pathology, Ari August, Rebecca Procopio, Christopher Rapuano, Jose Pulido

Wills Eye Hospital Papers

Purpose: ADAMTS18-related ocular pathology is rare with few described cases. Features include distinctive facies, refractive error, anterior segment dysgenesis, and retinal dystrophy. Previous patients were found to have ho- mozygous variants in ADAMTS18. Here, we present a patient with compound heterozygous ADAMTS18-related pathology and its associated findings. Observations: A 37-year-old male with a history of bilateral congenital nasolacrimal duct obstruction, dry eye syndrome, mild myopia, and accommodative esotropia presented to the Retina Service. He was found to have multiple features of anterior segment dysgenesis and retinal dystrophy, some of which have not been previously reported in association with ADAMTS18 variants. …

Discontiguous Recurrences Of Idh-Wildtype Glioblastoma Share A Common Origin With The Initial Tumor And Are Frequently Hypermutated, Malcolm F Mcdonald, Sricharan Gopakumar, Tareq A Juratli, Ilker Y Eyüpoglu, Ganesh Rao, Jacob J Mandel, Ali Jalali

Faculty, Staff and Students Publications

Glioblastoma is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after treatment. While most recurrences are local, patients rarely present with a new discontiguous focus of glioblastoma. Little is currently known about the genetic profile of discontiguous recurrences. In our institutional database, we identified 22 patients with targeted exome sequencing of pairs of initial and recurrent IDH-wildtype glioblastoma. Recurrences were classified as contiguous or discontiguous based on the presence or absence of T2 FLAIR signal connection to the initial site of disease on MRI. Exome analysis revealed shared driver and passenger mutations between discontiguous recurrences …

Adenosine-Sensitive Upper Septal Fascicular Ventricular Tachycardia Associated With Takotsubo Syndrome, Parker O'Neill, Daniel Underberg, Reginald Ho, Darius Farzad, Gregary Marhefka

Department of Medicine Faculty Papers

We describe a rare case of upper septal fascicular ventricular tachycardia (VT) associated with takotsubo syndrome that failed to convert with synchronized shock but converted to normal sinus rhythm after intravenous adenosine administration. The excess catecholamine state of takotsubo syndrome likely provided substrate for cyclic adenosine monophosphate–mediated triggered activity, causing fascicular VT.

Dna Methylation Profile In Buffy Coat Identifies Methylation Differences Between Cirrhosis With And Without Hepatocellular Carcinoma, Hyeyeun Lim, Hashem B El-Serag, Michelle Luster, Megan L Grove, Jinyoung Byun, Yuri Jung, Younghun Han, Eric Boerwinkle, Christopher I Amos, Aaron P Thrift

Faculty, Staff and Students Publications

Background/Objectives: Cirrhosis is the precursor to most cases of hepatocellular carcinoma (HCC). Understanding the mechanisms leading to the transition from cirrhosis to HCC and identifying key biomarkers is crucial to developing effective screening strategies and reducing HCC-related mortality. DNA methylation is associated with gene inactivation and plays an important role in physiological and pathological processes; however, its role in cirrhosis progression to HCC is unknown.

Methods: We performed genome-wide DNA methylation profiling using Illumina Infinium MethylationEPI BeadChip in pre-diagnostic samples from 22 cirrhosis patients who subsequently developed HCC and 22 cirrhosis patients who remained HCC-free during an average 4-year follow-up. …

Nitroglycerine For Retained Placenta: A Meta-Analysis Of Randomized Controlled Trials, Alessandro Petrecca, Gabriele Saccone, Vincenzo Berghella

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: To evaluate the effect of nitroglycerine on placenta delivery after retained placenta.

DESIGN: Systematic review with meta-analysis.

DATA SOURCES: MEDLINE, PROSPERO, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect, the Cochrane Library, Scielo were searched from their inception until February 2024.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included all randomized clinical trials comparing use of nitroglycerine (i.e. intervention group) with placebo or with no treatment (i.e. control group) given for retained placenta after vaginal delivery.

DATA SYNTHESIS: The primary outcome was rate of manual removal of the placenta. The summary measures were reported as relative risk (RR) or as mean difference (MD) with …

A Longer Duration Of Intravenous Antibiotic Treatment For Patients With Early Periprosthetic Joint Infections Is Not Associated With A Lower Failure Rate, Janneke Meijer, Alex Soriano, Wierd Zijlstra, Bas Ten Have, Saad Tarabichi, Paul Jutte, Javad Parvizi, Marjan Wouthuyzen-Bakker

Rothman Institute Papers

BACKGROUND: In recent years, many studies have demonstrated the efficacy of an early switch to oral antibiotics after surgical treatment in orthopedic-related infections. However, large analyses on periprosthetic joint infections (PJIs) are lacking.

MATERIAL AND METHODS: We conducted a retrospective observational multicenter study in patients diagnosed with an early post-operative PJI, defined as one occurringdebridement, antibiotics, and implant retention (DAIR). Patients from Europe and the USA were included. We took advantage of the fact that an early oral antibiotic switch is routine practice in Europe as opposed to a long duration of intravenous (IV) antibiotic treatment in the USA. Failure …

Hyperleukocytosis In A Neuroblastoma Patient After Treatment With Natural Killer T Cells Expressing A Gd2-Specific Chimeric Antigen Receptor And Il-15, Gengwen Tian, Amy N Courtney, Hangjin Yu, Saleh Bhar, Xin Xu, Gabriel A Barragán, Claudia Martinez Amador, Nisha Ghatwai, Michael S Wood, Deborah Schady, Antonino Montalbano, Shantan Reddy, Aoife M Roche, David De La Cerda, Donald Williams Parsons, Erica J Di Pierro, Frederic D Bushman, Andras Heczey, Leonid S Metelitsa

Faculty, Staff and Students Publications

The ability of immune cells to expand numerically after infusion distinguishes adoptive immunotherapies from traditional drugs, providing unique therapeutic advantages as well as the potential for unmanageable toxicities. Here, we describe a case of lethal hyperleukocytosis in a patient with neuroblastoma treated on phase 1 clinical trial (NCT03294954) with autologous natural killer T cells (NKTs) expressing a GD2-specific chimeric antigen receptor and cytokine interleukin 15 (GD2-CAR.15). This patient was the first to be treated on dose level (DL) 5 and the first patient whose product was restimulated with K562-derived artificial antigen-presenting cells (aAPCs) instead of autologous peripheral blood mononuclear cells …

Residual Traditional Risk In Non-Traditional Atherosclerotic Diseases, Federico Biscetti, Giorgia Polito, Maria Margherita Rando, Maria Anna Nicolazzi, Luis H. Eraso, Paul J. Dimuzio, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Surgery Faculty Papers

Individuals with chronic inflammatory and immune disorders are at an increased risk of atherosclerotic events and premature cardiovascular (CV) disease. Despite extensive literature exploring the relationship between "non-traditional" atherosclerotic conditions and CV risk, many aspects remain unresolved, including the underlying mechanisms promoting the "non-traditional CV risk", the development of an innovative and comprehensive CV risk assessment tool, and recommendations for tailored interventions. This review aims to evaluate the available evidence on key "non-traditional" CV risk-enhancer conditions, with a focus on assessing and managing CV risk factors. We conducted a comprehensive review of 412 original articles, narrative and systematic reviews, and …

Microrna 133a Regulates Squalene Epoxidase Expression In Colorectal Cancer Cells To Control Cell Proliferation And Cholesterol Production, Ji Su Mo, Santosh Lamichhane, Grinsun Sharma, Soo Cheon Chae

School of Medicine Faculty Publications

Background/Objectives: Colorectal cancer (CRC) is one of the most common cancers worldwide, with high incidence and mortality rates. MicroRNAs are endogenous and non-coding RNAs that play a pivotal role in the development and progression of various cancers by targeting specific genes. Previously, we identified MIR133A to be significantly decreased in human CRC tissues. This study aims to identify the relationship with SQLE, one of the candidate target genes of MIR133A, and study their interaction in CRC cells. Methods: Through the luciferase reporter assay, quantitative RT-PCR (qRT-PCR), and Western blot analysis. Results: We identified SQLE as a direct target gene of …

Advancing Monogenic Diabetes Research And Clinical Care By Creating A Data Commons: The Precision Diabetes Consortium (Predict), Michael E Mccullough, Lisa R Letourneau-Freiberg, Rochelle N Naylor, Siri Atma W Greeley, David T Broome, Mustafa Tosur, Raymond J Kreienkamp, Erin Cobry, Neda Rasouli, Toni I Pollin, Miriam S Udler, Liana K Billings, Cyrus Desouza, Carmella Evans-Molina, Suzi Birz, Brian Furner, Michael Watkins, Kaitlyn Ott, Samuel L Volchenboum, Louis H Philipson

Faculty, Staff and Students Publications

Monogenic diabetes mellitus (MDM) is a group of relatively rare disorders caused by pathogenic variants in key genes that result in hyperglycemia. Lack of identified cases, along with absent data standards, and limited collaboration across institutions have hindered research progress. To address this, the UChicago Monogenic Diabetes Registry (UCMDMR) and UChicago Data for the Common Good (D4CG) created a national consortium of MDM research institutions called the PREcision DIabetes ConsorTium (PREDICT). Following the D4CG model, PREDICT has successfully established a multicenter MDM data commons. PREDICT has created a consensus data dictionary that will be utilized to address critical gaps in …

Molecular Logic For Cellular Specializations That Initiate The Auditory Parallel Processing Pathways, Junzhan Jing, Ming Hu, Tenzin Ngodup, Qianqian Ma, Shu-Ning Natalie Lau, M Cecilia Ljungberg, Matthew J Mcginley, Laurence O Trussell, Xiaolong Jiang

Faculty, Staff and Students Publications

The cochlear nuclear complex (CN), the starting point for all central auditory processing, encompasses a suite of neuronal cell types highly specialized for neural coding of acoustic signals. However, the molecular logic governing these specializations remains unknown. By combining single-nucleus RNA sequencing and Patch-seq analysis, we reveal a set of transcriptionally distinct cell populations encompassing all previously observed types and discover multiple hitherto unknown subtypes with anatomical and physiological identity. The resulting comprehensive cell-type taxonomy reconciles anatomical position, morphological, physiological, and molecular criteria, enabling the determination of the molecular basis of the specialized cellular phenotypes in the CN. In particular, …

Toward Personalized Digital Experiences To Promote Diabetes Self-Management: Mixed Methods Social Computing Approach, Tavleen Singh, Kirk Roberts, Kayo Fujimoto, Jing Wang, Constance Johnson, Sahiti Myneni

Faculty, Staff and Student Publications

BACKGROUND: Type 2 diabetes affects nearly 34.2 million adults and is the seventh leading cause of death in the United States. Digital health communities have emerged as avenues to provide social support to individuals engaging in diabetes self-management (DSM). The analysis of digital peer interactions and social connections can improve our understanding of the factors underlying behavior change, which can inform the development of personalized DSM interventions.

OBJECTIVE: Our objective is to apply our methodology using a mixed methods approach to (1) characterize the role of context-specific social influence patterns in DSM and (2) derive interventional targets that enhance individual …

Genetics And Biology Of Pancreatic Ductal Adenocarcinoma, Haoqiang Ying, Alec C Kimmelman, Nabeel Bardeesy, Raghu Kalluri, Anirban Maitra, Ronald A Depinho

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) poses a grim prognosis for patients. Recent multidisciplinary research efforts have provided critical insights into its genetics and tumor biology, creating the foundation for rational development of targeted and immune therapies. Here, we review the PDAC genomic landscape and the role of specific oncogenic events in tumor initiation and progression, as well as their contributions to shaping its tumor biology. We further summarize and synthesize breakthroughs in single-cell and metabolic profiling technologies that have illuminated the complex cellular composition and heterotypic interactions of the PDAC tumor microenvironment, with an emphasis on metabolic cross-talk across cancer and …

Targeted Inhibition Of Aurora Kinase A Promotes Immune Checkpoint Inhibition Efficacy In Human Papillomavirus-Driven Cancers, Soma Ghosh, Madison P O'Hara, Pragya Sinha, Tuhina Mazumdar, Lacin Yapindi, Jagannadha K Sastry, Faye M Johnson

Faculty, Staff and Student Publications

Background: Human papillomavirus (HPV)-driven cancers include head and neck squamous cell carcinoma and cervical cancer and represent approximately 5% of all cancer cases worldwide. Standard-of-care chemotherapy, radiotherapy, and immune checkpoint inhibitors (ICIs) are associated with adverse effects and limited responses in patients with HPV-driven cancers. The integration of targeted therapies with ICIs may improve outcomes. In a previous study, we demonstrated that Aurora kinase A (AURKA, Aurora A) inhibitors lead to apoptosis of human HPV-positive cancer cells in vitro and in vivo. Here, we explored the potential of Aurora A inhibition to enhance response to ICIs in immune-competent …

Recurrent And Metastatic Head And Neck Cancer: Mechanisms Of Treatment Failure, Treatment Paradigms, And New Horizons, William T. Barham, Marshall Patrick Stagg, Rula Mualla, Michael Dileo, Sagar Kansara

School of Medicine Faculty Publications

Background: Head and neck cancer is a deadly disease with over 500,000 cases annually worldwide. Metastatic head and neck cancer accounts for a large proportion of the mortality associated with this disease. Many advances have been made in our understanding of the mechanisms of metastasis. The application of immunotherapy to locally recurrent or metastatic head and neck cancer has not only improved oncologic outcomes but has also provided valuable insights into the mechanisms of immune evasion and ultimately treatment failure. Objectives: This review paper will review our current understanding of biological mechanisms of treatment failure and metastasis. Published and ongoing …