Allergy and Immunology Commons^™

Braf V600e-Positive Mononuclear Cells In Blood At Diagnosis Portend Treatment Failure And Neurodegeneration In Pediatric Lch, Howard Lin, Akanksha Batajoo, Erin Peckham-Gregory, Daniel Zinn, Olive S Eckstein, Nader Kim El-Mallawany, Nitya Gulati, Zachary D Prudowsky, Brooks Scull, Jessica Velazquez, Harshal Abhyankar, Stephen J Simko, Daria Vakula, Ryan Fleischmann, Vivekanudeep Karri, M John Hicks, Kevin E Fisher, Choladda V Curry, Angshumoy Roy, Deborah Schiff, Kenneth M Heym, Michael E Scheurer, D Williams Parsons, Miriam Merad, Tsz-Kwong Man, Kenneth L Mcclain, Jennifer Picarsic, Carl E Allen

Faculty, Staff and Students Publications

Langerhans cell histiocytosis (LCH) is a myeloid neoplastic disorder driven by mitogen-activated protein kinase (MAPK) activation in hematopoietic cells. Historically, LCH has been staged according to involvement of "risk organs" (bone marrow, liver, and spleen), based on risk of death. With improvements in supportive care and efficacy of MAPK pathway inhibitors, patients with LCH now rarely die. However, most patients with LCH with multisystem disease are not cured with current front-line chemotherapy, and treatment failure is associated with long-term morbidity, including LCH-associated neurodegeneration (LCH-ND). In this study, we evaluated the impact of extent of LCH at presentation, tumor genotype, and …

Infantile Pyknocytosis Revisited: Possible Familial Trend In A Study Of 9 Patients, Aileen Y Hu, Amy M Coffey, Jyotinder N Punia, Andrea N Marcogliese, Choladda V Curry, M Tarek Elghetany

Faculty, Staff and Students Publications

Context.—: Infantile pyknocytosis (IP) is an uncommon cause of transient neonatal hemolytic anemia and hyperbilirubinemia occurring in approximately 10% of cases of unexplained neonatal hemolytic anemia.

Objective.—: To study cases of IP with focus on long-term follow-up, perinatal events, and family history.

Design.—: Cases were prospectively identified during review of peripheral blood smears for neonatal hyperbilirubinemia during an 11-year period. Clinical and laboratory parameters, follow-up data, and family history were recorded.

Results.—: Nine cases of IP were identified from the morphologic recognition of pyknocytes and clinical and laboratory evidence of hemolysis, and included 6 males and 3 females. Age at …

Alfred Russel Wallace Notes 37. What About Wallace On Vaccination . . . ?, Charles H. Smith

Faculty/Staff Personal Papers

Best known for his natural history studies on evolution and biogeography, Alfred Russel Wallace (1823−1913) had a significant second career as a social critic. One of his most controversial stances was his position on (smallpox) vaccination. Anti-vaxxers of the present frequently bring up his name as a resource for their side, but the situation is not so easily reducible to that.

Genomic Reporting Practices Across 5 Molecular Disciplines: A Study From The College Of American Pathologists, Larissa V Furtado, Annette S Kim, Ann M Moyer, Joel T Moncur, Rena R Xian, Angshumoy Roy, Avni B Santani, Yassmine Akkari, Karl V Voelkerding, Rhona J Souers, Jaimie Halley, Glenn E Palomaki

Faculty, Staff and Students Publications

Context.—: Genomic reports are primarily organized in a narrative and unstructured format with variations in content and format. Regulatory requirements and professional guidelines for genetic test reporting exist but provide little guidance for effective communication of information.

Objective.—: To assess clinical genomic reporting practices across 5 disciplines within molecular diagnostics, including germline, somatic solid tumors, somatic hematologic malignancies, pharmacogenomics, and prenatal cell-free DNA screening.

Design.—: Reporting practices were assessed by using a structured review of clinical genomic reports from multiple laboratories in 5 molecular disciplines spanning different practice settings. Report content was reviewed by the presence/absence of from 27 to …

Gut Virome Profile In New Onset Treatment Naïve Saudi Children With Ulcerative Colitis, Mohammad El Mouzan, Tor C Savidge, Ahmed Al Sarkhy, Shyam Badu, Badr Alsaleem, Mohammad Al Mofarreh, Abdullah Almasood, Asaad Assiri

Faculty, Staff and Students Publications

Background: Gut microbiome imbalance is well established in ulcerative colitis (UC) in Western populations. Significantly less is known about the gut virome and whether geography impacts the UC-associated microbiome. The aim of this study was to characterize gut bacteriophage changes, as well as to identify phage-bacterial associations that can serve as potential biomarkers of UC.

Methods: Twenty children with UC and 20 healthy controls were enrolled in the study. Inclusion criteria included newly diagnosed treatment-naïve children with UC with no antibiotic exposure for at least six months prior to sample collection. Deoxyribonucleic acid (DNA) was extracted from stool and rectal …

Impact Of Optimal Medical Therapy In Heart Failure Certification For Hospitalists On Guideline-Directed Medical Therapy Utilization, Farhan Ishaq, Duc T Nguyen, Edward A Graviss, Ebun Ebunlomo, Arvind Bhimaraj, Nadia Fida

Faculty, Staff and Students Publications

Background: Significant gaps in guideline-directed medical therapy (GDMT) for heart failure (HF) stem from shortages of cardiologists and advanced HF providers, as well as a lack of optimal HF management knowledge among hospitalists. This study compared the impact of optimal medical therapy in HF (OMT-HF) certification on GDMT implementation and patient outcomes between an intervention group (IG) of hospitalists and a standard-of-care comparison group (SOC-CG).

Aim: To evaluate if OMT-HF has a difference in GDMT and patients in outcomes between IG and SOC-CG.

Methods: This study was implemented from November 2022 to May 2023. Hospitalized cardiology patients with HF and …

A Family Navigator Improves Post-Discharge Treatment Adherence Among Adolescents With Anorexia Nervosa: A Pilot Study, Elizabeth V Franklin, Margaret Mathias, Duc T Nguyen, Albert C Hergenroeder, Constance M Wiemann

Faculty, Staff and Students Publications

Background: Adolescent patients with Anorexia Nervosa (AN) and Atypical Anorexia Nervosa (AAN) admitted to an inpatient medical unit are at risk of relapse if they do not receive follow up treatment. Yet treatment adherence following discharge remains poor. One possible reason for poor treatment adherence is insufficient support for parents. This pilot study explored the preliminary impact of a novel family navigator (FN) intervention on adolescent patient treatment adherence following inpatient care.

Methods: This was a pilot prospective study with a retrospective control cohort. Twenty-three adolescent patients with AN or AAN discharging from an Adolescent Medicine inpatient medical unit whose …

Antibiofilm Properties Of 4-Hydroxy-3-Methyl-2-Alkenylquinoline, A Novel Burkholderia-Derived Alkaloid, Mckinley D Williams, Taylor R Sweeney, Sabrina Trieu, Ravi Orugunty, Abdelahhad Barbour, Fereshteh Younesi, Michael Glogauer, Nopakorn Hansanant, Ronald Shin, Shi-En Lu, Kevin Cao, Abraham Tenorio, Sigmund J Haidacher, Anthony M Haag, Thomas D Horvath, Leif Smith

Faculty, Staff and Students Publications

Biofilms are an important colonization mechanism employed by several microbial species to better establish themselves and monopolize the acquisition of resources across different environs. Some bacteria have evolved specialized metabolites that, when secreted, disrupt the formation and stability of biofilms generated by competing heterospecies, providing the producing organism with an ecological advantage. Soil-derived species are probable candidates for the identification of such compounds, given the intense level of competition that occurs within the terrestrial ecosystem. The MS14 strain of Burkholderia contaminans isolated from soil in Mississippi has previously been shown to produce antimicrobial compounds like occidiofungin and ornibactin. In this …

Identification And Preclinical Assessment Of Novel Therapeutic Modalities In Environmental Exposure-Induced Lung Disease, Aaron D. Schwab

Theses & Dissertations

Environmental lung diseases are preventable respiratory conditions either caused or made worse by inhaled environmental exposures. Contemporarily, environmental lung diseases are most associated with workplace exposures given specific occupational processes aerosolize inflammatory agents that can be inhaled at high concentrations. Although a considerable amount is known regarding immunoglobulin (Ig)E-mediated responses to environmental exposures, little is known about non-IgE mediated respiratory conditions resulting from lipopolysaccharide (LPS)-enriched organic dust exposure(s). Chronic respiratory diseases such as asthma, hypersensitivity pneumonitis, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis have all been identified as environmental lung diseases caused or exacerbated by such environmental dusts. Therapeutic …

Drug-Induced Hypersensitivity Syndrome Resulting In Hepatotoxicity And Epstein-Barr Virus Reactivation Following Initiation Of Levetiracetam, Zechariah Jung, Xavier Zonna, Samuel J. Wlasowicz, Conor Banta, Lawrence Canale, Joseph Bielecki

Advances in Clinical Medical Research and Healthcare Delivery

A 28-year-old male with a past medical history of alcohol abuse had new-onset seizures suspected to be caused by alcohol use. Twelve days after starting levetiracetam for seizure prophylaxis, he began to develop a pruritic rash, darkening of his urine, periods of jaundice, and hot flashes that correlated with the timing of his levetiracetam dosing. He was subsequently found to have lymphocyte-predominant leukocytosis, elevated aminotransferases, and alkaline phosphatase. Following discontinuation of his levetiracetam, he was found to have positive Epstein-Barr virus (EBV) serology suggestive of reactivation. This case demonstrates levetiracetam as a rare cause of drug-induced hypersensitivity syndrome (DIHS) along …

Interferon Regulatory Factor 3 In Interferon Gamma Receptor Signaling And Cancer Immunology, Zachary P. Guinn

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Every year millions of people die from cancer throughout the world, and tens of millions of people are diagnosed with cancer worldwide. When surgery is not an option, treatment options commonly rely on the host immune system for optimal treatment efficacy. The expression of Interferon gamma (IFN-γ) by host immune cells is often associated with favorable antitumor immune responses. How IFN-γ is optimally induced in immune cells, and how IFN-γ promotes the transcription of genes downstream of the Interferon gamma receptor (IFNGR) is incompletely understood. Understanding how to induce immune cells to express optimal IFN-γ …

Case Report: A Case Of Transient Dress Syndrome (Drug Rash With Eosinophilia And Systemic Symptoms), Dip Patel, James Espinosa, Alan Lucerna

Rowan-Virtua Research Day

We report a case of a 41-year-old female with a history of hypertension who presented with fever and a diffuse erythematous rash after taking trimethoprim-sulfamethoxazole (TMP-SMX) for an ear infection. Due to her symptoms, mild eosinophilia, and elevated liver function tests, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) was suspected. Although the patient’s rash had resolved by the time of initial evaluation, it recurred overnight, reinforcing suspicion for DRESS syndrome. TMP-SMX was discontinued, and acetylcysteine was administered due to the patient’s high-dose use of acetaminophen in the days prior to her hospital presentation. Infectious and autoimmune workups were negative. …

Case Report: Cold Urticaria Diagnosed In The Emergency Department, Philip Carhart, James Espinosa, Alan Lucerna

Rowan-Virtua Research Day

Cold urticaria can be primary (idiopathic) or can be due to underlying hematologic or infectious diseases. Here we present the case of a young female patient with no past medical history who was diagnosed with cold urticaria in the emergency department setting, using a cold stimulation test. Most cases are idiopathic. The reaction can be triggered in individual cases by exposure to cold objects or to generalized cold ambient temperatures, as was the case in the patient presented here. The physical response is most commonly pruritic wheals (urticaria). However, more severe symptoms may occur up to angioedema with hoarseness and …

Case Report: Alpha Gal Syndrome, Eric Haljasmaa, David Parkes, Wayne Tamaska

Rowan-Virtua Research Day

We report a case of a 40-year-old male who presented with sensation of throat closing and shortness of breath while at work at a meat processing facility. The differential diagnosis of shortness of breath is throat closing includes, but is not limited to, allergic reactions to antibiotics in meat, allergy to food additives, Symptom triggers are useful in identifying causes and a good supporting history and exposures can help with diagnosis. In this case, the patient had a known diagnosis of Alpha-gal syndrome (AGS) which is a tick-bite associated, possibly life-threatening immunoglobin E-mediated (IgE) hypersensitivity to galactose-alpha-1,3-galactose (alpha-gal). The patient …

Case Report: Lamotrigine-Induced Rash In An Adult Patient, Dhruvin Patel, James Espinosa, Alan Lucerna

Rowan-Virtua Research Day

Lamotrigine (Lamictal®) is a commonly prescribed anticonvulsant and mood-stabilizing medication. One of the rare but serious adverse effects of lamotrigine is the development of a drug-induced rash, which can be potentially life-threatening. This case report highlights the occurrence of a drug-induced rash in a 33-year-old female patient who was prescribed lamotrigine for the management of bipolar disorder. The patient presented with a characteristic rash, and following timely intervention, the rash resolved without complications. This case emphasizes the importance of monitoring for early signs of rash in patients receiving lamotrigine and outlines management strategies.

Allergies Coinciding With Central Sensitization Syndromes (Access), Jacqueline Morey, Alemu Fite, Carl Lauter, Matthew Sims

Posters

Significance of Reported Allergies: Many reported drug allergies are mislabeled side effects or misinterpretations, leading to suboptimal treatment, antibiotic resistance, and worse patient outcomes.¹

Central Sensitization Syndromes (CSS): CSSs are chronic pain conditions linked to altered sensory perception, including pain, fatigue, and neurologic dysfunction.² These patients may be more likely to misattribute medication side effects as allergies.

Previous Findings & Hypothesis: Prior research found high allergy reporting in interstitial cystitis and fibromyalgia—both CSS conditions.⁴ We hypothesized that other CSS diagnoses also correlate with increased allergy reporting, emphasizing the need for better allergy evaluation.

Intratumoral Fibrin As A Novel Immunomodulatory Factor In Pancreatic Ductal Adenocarcinoma, Mazharul Karim

Open Access Theses & Dissertations

In-situ coagulation is a common clinical feature of pancreatic ductal adenocarcinoma (PDAC) that presents a highly thrombotic and crosslinked insoluble fibrin (x-fibrin)-laden tumor stroma (FibTS). However, the specific impact of FibTS on immune cells behavior remains largely unexplored in this poorly infiltrated tumor. We aimed to elucidate how FibTS in PDAC regulates immune cell infiltration, polarization, and crosstalk that favors immunosuppressive microenvironment and tumor growth. We characterized human PDAC tissues by multiplex immunostaining and checked the spatial distribution of immune cells based on the presence of x-fibrin. We investigated how FibTS influences the infiltration of tumor-associated macrophage (TAM) and T-cell …

Natural Killer T Cell-Mediated Control Of Francisella Tularensis-Induced Cytokine Storm Syndrome, Cameron M. Torres

Open Access Theses & Dissertations

Inflammation is critical for the effective clearance of viral and bacterial challenges, while simultaneously a mechanism utilized by many highly infectious pathogens to cause disease. The bacterium Francisella tularensis, the causative agent of human tularemia, elicits a cytokine storm, wherein the immune system over-responds to the presence of the bacterium causing a dysregulated release of proinflammatory and regulatory cytokines. Without treatment, tularemia mortality can be as high as 30%, with inhalation of as few as 10 CFUs inducing respiratory tularemia. Natural Killer T (NKT) cells are innate-like T lymphocytes with a diverse array of regulatory functions. Unlike conventional T cells, …

Macrophage-Mediated Il-6 Signaling Drives Ryanodine Receptor-2 Calcium Leak In Postoperative Atrial Fibrillation, Joshua A Keefe, Yuriana Aguilar-Sanchez, J Alberto Navarro-Garcia, Isabelle Ong, Luge Li, Amelie Paasche, Issam Abu-Taha, Marcel A Tekook, Florian Bruns, Shuai Zhao, Markus Kamler, Ying H Shen, Mihail G Chelu, Na Li, Dobromir Dobrev, Xander Ht Wehrens

Faculty, Staff and Students Publications

Postoperative atrial fibrillation (poAF) is AF occurring days after surgery, with a prevalence of 33% among patients undergoing open-heart surgery. The degree of postoperative inflammation correlates with poAF risk, but less is known about the cellular and molecular mechanisms driving postoperative atrial arrhythmogenesis. We performed single-cell RNA-seq comparing atrial nonmyocytes from mice with and without poAF, which revealed infiltrating CCR2+ macrophages to be the most altered cell type. Pseudotime trajectory analyses identified Il-6 as a gene of interest driving in macrophages, which we confirmed in pericardial fluid collected from human patients after cardiac surgery. Indeed, macrophage depletion and macrophage-specific Il6ra …

Ai Model For Predicting Asthma Prognosis In Children, Elham Sagheb, Chung-Il Wi, Katherine S King, Bhavani Singh Agnikula Kshatriya, Euijung Ryu, Hongfang Liu, Miguel A Park, Hee Yun Seol, Shauna M Overgaard, Deepak K Sharma, Young J Juhn, Sunghwan Sohn

Faculty, Staff and Student Publications

BACKGROUND: Childhood asthma often continues into adulthood, but some children experience remission. Utilizing electronic health records (EHRs) to predict asthma prognosis can aid health care providers and patients in developing effective prioritized care plans.

OBJECTIVE: We aimed to develop artificial intelligence (AI) models using various clinical variables extracted from EHRs to predict childhood asthma prognosis (remission vs no remission) in different age groups.

METHODS: We developed AI models utilizing patients' EHRs during the first 6, 9, or 12 years of their lives to predict their asthma prognosis status at ages 6 to 9, 9 to 12, or 12 to 15 …