Diseases Commons^™

Identification And Initial Validation Of Maximal Tumor Area As A Novel Prognostic Factor For Overall And Disease-Free Survival In Patients With Resectable Colon Cancer: A Retrospective Study, Fei-Long Ning, Wan-Jie Gu, Lin-Zheng Dai, Wan-Ying Du, Yong-Ji Zeng, Jia-Kui Zhang, Masanobu Abe, Yan-Long Liu, Rui Zhang, Chun-Dong Zhang

Faculty, Staff and Students Publications

BACKGROUND: The tumor area may be a potential prognostic indicator. The present study aimed to determine and validate the prognostic value of tumor area in curable colon cancer.

METHODS: This retrospective study included a training and validation cohorts of patients who underwent radical surgery for colon cancer. Independent prognostic factors for overall survival (OS) and disease-free survival (DFS) were identified using Cox proportional hazards regression models. The prognostic discrimination was evaluated using the integrated area under the receiver operating characteristic curves (iAUCs) for prognostic factors and models. The prognostic discrimination between tumor area and other individual factors was compared, along …

Idiopathic Dilatation Of The Right Atrium: Diagnosis And Management, Ljiljana Rankovic-Nicic, Milica Dragicevic-Antonic, Goran Loncar, Masa Petrovic, Zelimir Antonic, Milovan Bojic

The Texas Heart Institute Journal

Idiopathic dilatation of the right atrium is a rare condition with an unknown etiology. It is characterized by a significant enlargement of the right atrium without the presence of other valvopathies, intracardiac shunts, or pulmonary hypertension. This report presents the case of a 50-year-old woman with a significantly enlarged right atrium that was identified at birth; however, a definitive diagnosis was made later in life. The patient did not have any genetic diseases. Through the help of regular follow-up, anticoagulant therapy, previous radio-frequency ablation, and antiarrhythmic medications, she was able to carry a pregnancy to full term and live a …

Human Intestinal Organoids From Cronkhite-Canada Syndrome Patients Reveal Link Between Serotonin And Proliferation, Victoria Poplaski, Carolyn Bomidi, Amal Kambal, Hoa Nguyen-Phuc, Sara C Di Rienzi, Heather A Danhof, Xi-Lei Zeng, Linda A Feagins, Nan Deng, Eduardo Vilar, Florencia Mcallister, Cristian Coarfa, Soyoun Min, Hyun Jung Kim, Richa Shukla, Robert Britton, Mary K Estes, Sarah E Blutt

Faculty, Staff and Student Publications

Cronkhite-Canada Syndrome (CCS) is a rare, noninherited polyposis syndrome affecting 1 in every million individuals. Despite over 50 years of CCS cases, the etiopathogenesis and optimal treatment for CCS remains unknown due to the rarity of the disease and lack of model systems. To better understand the etiology of CCS, we generated human intestinal organoids (HIOs) from intestinal stem cells isolated from 2 patients. We discovered that CCS HIOs are highly proliferative and have increased numbers of enteroendocrine cells producing serotonin (also known as 5-hydroxytryptamine or 5HT). These features were also confirmed in patient tissue biopsies. Recombinant 5HT increased proliferation …

Establishment Of A Consensus Protocol To Explore The Brain Pathobiome In Patients With Mild Cognitive Impairment And Alzheimer’S Disease: Research Outline And Call For Collaboration, Richard Lathe, Nikki M Schultek, Brian J Balin, Garth D Ehrlich, Lavinia Alberi Auber, George Perry, Edward B Breitschwerdt, David B Corry, Richard L Doty, Robert A Rissman, Peter L Nara, Ruth Itzhaki, William A Eimer, Rudolph E Tanzi, Intracell Research Group Consortium Collaborators

Faculty, Staff and Students Publications

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will …

Obesity Dominates Early Effects On Cardiac Structure And Arterial Stiffness In People With Type 2 Diabetes, Layla A Abushamat, Daniel Enge, Takashi Fujiwara, Michal Schäfer, Ethan W Clark, Erin K Englund, Rebecca L Scalzo, Aspen Johnston, Deirdre Rafferty, Irene E Schauer, Mary O Whipple, Kendall Hunter, Amy G Huebschmann, Kristen J Nadeau, Kelly Jarvis, Alex J Barker, Judith G Regensteiner, Jane E B Reusch

Faculty, Staff and Students Publications

OBJECTIVE: Type 2 diabetes (T2D) and obesity are global epidemics leading to excess cardiovascular disease (CVD). This study investigates standard and novel cardiac MRI parameters to detect subclinical cardiac and central vascular dysfunction in inactive people with and without T2D.

METHODS: Physically inactive age and BMI-similar premenopausal women and men with ( n  = 22) and without [ n  = 34, controls with overweight/obesity (CWO)] uncomplicated T2D were compared to an age-similar and sex-similar reference control cohort ( n  = 20). Left ventricular (LV) structure, function, and aortic stiffness were assessed by MRI. Global arterial pulse wave velocity (PWV) was …

Bone Health In Children With Recurrent And Chronic Pancreatitis: A Multi-Center Cross Sectional Analysis, Maisam Abu-El-Haija, Lindsey Hornung, Kate Ellery, Douglas S Fishman, Tanja Y Gonska, Cheryl Gariepy, Mark Lowe, Katie Larson Ode, Asim Maqbool, Maria Mascarenhas, Veronique D Morinville, Chee Y Ooi, Emily R Perito, Sarah Jane Schwarzenberg, Zachary M Sellers, Babette S Zemel, Ying Yuan, Fuchenchu Wang, Aliye Uc, Heidi J Kalkwarf

Faculty, Staff and Students Publications

BACKGROUND/OBJECTIVES: Bone health of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) is not well studied.

METHODS: This retrospective study was performed at three sites and included data from INSPPIRE-2.

RESULTS: Of the 87 children in the study: 46 had ARP (53%), 41 had CP (47%). Mean age was 13.6 ± 3.9 years at last DXA scan. The prevalence of low height-for-age (Z-score < -2) (13%, 10/78) and low bone mineral density (BMD) adjusted for height (Z-score < -2) (6.4%, 5/78) were higher than a healthy reference sample (2.5%, p < 0.0001 and p = 0.03, respectively).

CONCLUSION: Children with ARP or CP have lower height and BMD than healthy peers. Attention to deficits in growth and bone mineral accrual in children with pancreatic disease is warranted.

“Is My Brain Ever Going To Work Fully Again?”: Challenges And Needs Of Cancer Survivors With Persistent Cancer-Related Cognitive Impairment, Darren Haywood, Evan Dauer, Frank D. Baughman, Blake J. Lawrence, Susan L. Rossell, Nicolas H. Hart, Moira O’Connor

Research outputs 2022 to 2026

Many cancer survivors experience cognitive impairments that impact memory, concentration, speed of information processing, and decision making. These impairments, collectively known as cancer-related cognitive impairments (CRCIs), are a key domain of unmet needs and can significantly impact a cancer survivor’s identity and quality of life. However, there are no purpose-built, multi-domain, needs assessment tools specifically for CRCI. The development of such tools requires an in-depth understanding of cancer survivors’ CRCI-specific challenges and associated needs. This study explored the challenges and associated needs of cancer survivors with persistent CRCI. An in-depth qualitative design using semi-structured interviews with (a) cancer survivors with …

Improving Outcomes For Infants After Cardiopulmonary Bypass Surgery For Congenital Heart Disease: A Commentary On Recent Randomized Controlled Trials, Luregn J Schlapbach, Kristen S Gibbons, Warwick Butt, Prince J Kannankeril, Jennifer S Li, Kevin D Hill

Faculty, Staff and Students Publications

The recent NITRIC and STRESS trials demonstrate opportunities to perform pragmatic large randomized trials in congenital heart disease. We discuss lessons learnt from these trials which can inform future trial design and conduct in the field of pediatric heart surgery.

Health-Related Quality Of Life In A Systematically Assessed Cohort Of Children And Adults With Urea Cycle Disorders, Chaya N Murali, John R Barber, Robert Mccarter, Anqing Zhang, Natalie Gallant, Kara Simpson, Naghmeh Dorrani, Greta N Wilkening, Ron D Hays, Uta Lichter-Konecki, Members Of The Urea Cycle Disorders Consortium, Lindsay C Burrage, Sandesh C S Nagamani

Faculty, Staff and Students Publications

PURPOSE: Individuals with urea cycle disorders (UCDs) may develop recurrent hyperammonemia, episodic encephalopathy, and neurological sequelae which can impact Health-related Quality of Life (HRQoL). To date, there have been no systematic studies of HRQoL in people with UCDs.

METHODS: We reviewed HRQoL and clinical data for 190 children and 203 adults enrolled in a multicenter UCD natural history study. Physical and psychosocial HRQoL in people with UCDs were compared to HRQoL in healthy people and people with phenylketonuria (PKU) and diabetes mellitus. We assessed relationships between HRQoL, UCD diagnosis, and disease severity. Finally, we calculated sample sizes required to detect …

Monitoring The Treatment Of Urea Cycle Disorders Using Phenylbutyrate Metabolite Analyses: Still Many Lessons To Learn, Kevin E Glinton, Charles G Minard, Ning Liu, Qin Sun, Sarah H Elsea, Lindsay C Burrage, Sandesh C S Nagamani

Faculty, Staff and Students Publications

Medications that elicit an alternate pathway for nitrogen excretion such as oral sodium phenylbutyrate (NaPBA) and glycerol phenylbutyrate (GPB) and intravenous sodium phenylacetate (NaPAA) are important for the management of urea cycle disorders (UCDs). Plasma concentrations of their primary metabolite, phenylacetate (PAA), as well as the ratio of PAA to phenylacetylglutamine (PAGN) are useful for guiding dosing and detecting toxicity. However, the frequency of toxic elevations of metabolites and associated clinical covariates is relatively unknown. A retrospective analysis was conducted on 1255 plasma phenylbutyrate metabolite measurements from 387 individuals. An additional analysis was also conducted on a subset of 68 …

Geographic Variation In Late-Stage Cervical Cancer Diagnosis, Itunu O Sokale, Aaron P Thrift, Jane Montealegre, Victor Adekanmbi, Onyema G Chido-Amajuoyi, Ann Amuta, Lorraine R Reitzel, Abiodun O Oluyomi

Faculty, Staff and Students Publications

IMPORTANCE: There are stark disparities in cervical cancer burden in the United States, notably by race and ethnicity and geography. Late-stage diagnosis is an indicator of inadequate access to and utilization of screening.

OBJECTIVE: To identify geospatial clusters of late-stage cervical cancer at time of diagnosis in Texas.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional study used incident cervical cancer data from the Texas Cancer Registry from 2014 to 2018 of female patients aged 18 years or older. Late-stage cervical cancer cases were geocoded at the census tract level (n = 5265) using their residential coordinates (latitude and longitude) at …

Political Ideology And Trust In Government Health Agencies For Cancer Information, Onyema G Chido-Amajuoyi, Henry K Onyeaka, Itunu O Sokale, Somto Nwani, Carlos H Barcenas, Hermioni L Amonoo, Sanjay Shete

Faculty, Staff and Students Publications

This cross-sectional study assesses the association between political ideology and trust in government health agencies for cancer information.

Epidemiology Of Giardiasis And Assemblages A And B And Effects On Diarrhea And Growth Trajectories During The First 8 Years Of Life: Analysis Of A Birth Cohort In A Rural District In Tropical Ecuador, Tannya Sandoval-Ramírez, Victor Seco-Hidalgo, Evelyn Calderon-Espinosa, Diana Garcia-Ramon, Andrea Lopez, Manuel Calvopiña, Irene Guadalupe, Martha Chico, Rojelio Mejia, Irina Chis Ster, Philip J Cooper

Faculty, Staff and Students Publications

BACKGROUND: There are limited longitudinal data on the acquisition of Giardia lamblia infections in childhood using molecular assays to detect and type assemblages, and measure effects of infections on diarrhea risk and childhood growth.

METHODS: We analysed stool samples from a surveillance sample within a birth cohort in a rural district in tropical Ecuador. The cohort was followed to 8 years of age for the presence of G. lamblia in stools by quantitative PCR and A and B assemblages by Taqman assay or Sanger sequencing. We explored risk factors associated with infection using generalized estimating equations applied to longitudinal binary …

Protein Advanced Glycation End Products And Their Implications In Pancreatic Cancer, Lakmini Senavirathna, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

Protein advanced glycation end products (AGE) formed by nonenzymatic glycation can disrupt the normal structure and function of proteins, and stimulate the receptor for AGEs (RAGE), triggering intricate mechanisms that are etiologically related to various chronic diseases, including pancreatic cancer. Many common risk factors of pancreatic cancer are the major sources for the formation of protein AGEs and glycative stress in the human body. Abnormal accumulation of protein AGEs can impair the cellular proteome and promote AGE-RAGE driven pro-inflammatory signaling cascades, leading to increased oxidative stress, protease resistance, protein dysregulation, transcription activity of STAT, NF-κB, and AP-1, aberrant status in …

Untargeted Metabolomic Analysis Investigating Links Between Unprocessed Red Meat Intake And Markers Of Inflammation, Alexis C Wood, Goncalo Graca, Meghana Gadgil, Mackenzie K Senn, Matthew A Allison, Ioanna Tzoulaki, Philip Greenland, Timothy Ebbels, Paul Elliott, Mark O Goodarzi, Russell Tracy, Jerome I Rotter, David Herrington

Faculty, Staff and Students Publications

BACKGROUND: Whether red meat consumption is associated with higher inflammation or confounded by increased adiposity remains unclear. Plasma metabolites capture the effects of diet after food is processed, digested, and absorbed, and correlate with markers of inflammation, so they can help clarify diet-health relationships.

OBJECTIVE: To identify whether any metabolites associated with red meat intake are also associated with inflammation.

METHODS: A cross-sectional analysis of observational data from older adults (52.84% women, mean age 63 ± 0.3 y) participating in the Multi-Ethnic Study of Atherosclerosis (MESA). Dietary intake was assessed by food-frequency questionnaire, alongside C-reactive protein (CRP), interleukin-2, interleukin-6, fibrinogen, …

Time To Consider The Potential Role Of Alternative Resistance Training Methods In Cancer Management?, Francesco Bettariga, Chris Bishop, Dennis R. Taaffe, Daniel A. Galvão, Luca Maestroni, Robert U. Newton

Research outputs 2022 to 2026

Exercise has emerged as fundamental therapeutic medicine in the management of cancer. Exercise improves health-related outcomes, including quality of life, neuromuscular strength, physical function, and body composition, and it is associated with a lower risk of disease recurrence and increased survival. Moreover, exercise during or post cancer treatments is safe, can ameliorate treatment-related side effects, and may enhance the effectiveness of chemotherapy and radiation therapy. To date, traditional resistance training (RT) is the most used RT modality in exercise oncology. However, alternative training modes, such as eccentric, cluster set, and blood flow restriction are gaining increased attention. These training modalities …

Gastrointestinal Infections Modulate The Risk For Insulin Autoantibodies As The First-Appearing Autoantibody In The Teddy Study, Maria Lönnrot, Kristian F Lynch, Marian Rewers, Åke Lernmark, Kendra Vehik, Beena Akolkar, William Hagopian, Jeffrey Krischer, Rickhard A Mcindoe, Jorma Toppari, Anette-G Ziegler, Joseph F Petrosino, Richard Lloyd, Heikki Hyöty, Teddy Study Group

Faculty, Staff and Students Publications

OBJECTIVE: To investigate gastrointestinal infection episodes (GIEs) in relation to the appearance of islet autoantibodies in The Environmental Determinants of Diabetes in the Young (TEDDY) cohort.

RESEARCH DESIGN AND METHODS: GIEs on risk of autoantibodies against either insulin (IAA) or GAD (GADA) as the first-appearing autoantibody were assessed in a 10-year follow-up of 7,867 children. Stool virome was characterized in a nested case-control study.

RESULTS: GIE reports (odds ratio [OR] 2.17 [95% CI 1.39-3.39]) as well as Norwalk viruses found in stool (OR 5.69 [1.36-23.7]) at(OR 0.48 [0.35-0.68]). GIE reports at any other age were associated with an increase in …

Sarcopenia Is Associated With Osteopenia And Impaired Quality Of Life In Children With Genetic Intrahepatic Cholestatic Liver Disease, Julia M Boster, Nathan P Goodrich, Cathie Spino, Kathleen M Loomes, Estella M Alonso, Binita M Kamath, Ronald J Sokol, Saul Karpen, Alexander Miethke, Benjamin L Shneider, Jean P Molleston, Rohit Kohli, Simon P Horslen, Philip Rosenthal, Pamela L Valentino, Jeffrey H Teckman, Thomas N Hangartner, Shikha S Sundaram

Faculty, Staff and Students Publications

BACKGROUND: Sarcopenia occurs in pediatric chronic liver disease, although the prevalence and contributing factors in genetic intrahepatic cholestasis are not well-described. The objective of this study was to measure muscle mass in school-aged children with genetic intrahepatic cholestasis and assess relationships between sarcopenia, clinical variables, and outcomes.

METHODS: Estimated skeletal muscle mass (eSMM) was calculated on dual-energy x-ray absorptiometry obtained in a Childhood Liver Disease Research Network study of children with bile acid synthesis disorders(BASD) alpha-1 antitrypsin deficiency (a1ATd), chronic intrahepatic cholestasis (CIC), and Alagille syndrome (ALGS). Relationships between eSMM, liver disease, and transplant-free survival were assessed.

RESULTS: eSMM was …

Relationships Among Intragastric Meal Distribution During Gastric Emptying Scintigraphy, Water Consumption During Water Load Satiety Testing, And Symptoms Of Gastroparesis, Henry P Parkman, Laura A Wilson, Paul Silver, Alan H Maurer, Irene Sarosiek, Robert S Bulat, Braden Kuo, Madhusudan Grover, Gianrico Farrugia, Bruno P Chumpitazi, Robert J Shulman, Zubair Malik, Laura A Miriel, James Tonascia, Frank Hamilton, Thomas L Abell, Pankaj J Pasricha, Richard W Mccallum, Kenneth L Koch, Niddk Gastroparesis Clinical Research Consortium

Faculty, Staff and Students Publications

Gastric emptying scintigraphy (GES) measures total gastric retention after a solid meal and can assess intragastric meal distribution (IMD). Water load satiety test (WLST) measures gastric capacity. Both IMD immediately after meal ingestion [ratio of proximal gastric counts after meal ingestion to total gastric counts at time 0 (IMD⁰)] and WLST (volume of water ingested over 5 min) are indirect measures of gastric accommodation. In this study, IMD⁰ and WLST were compared with each other and to symptoms of gastroparesis to gauge their clinical utility for assessing patients with symptoms of gastroparesis. Patients with symptoms of gastroparesis …

Preterm Pigs Fed Donor Human Milk Have Greater Liver Β-Carotene Concentrations Than Pigs Fed Infant Formula, Nancy E Moran, Joshua Wade, Rachel Stroh, Barbara Stoll, Gregory Guthrie, Amy B Hair, Douglas G Burrin

Faculty, Staff and Students Publications

BACKGROUND: Milk carotenoids may support preterm infant health and neurodevelopment. Infants fed human milk often have higher blood and tissue carotenoid concentrations than infants fed carotenoid-containing infant formula (IF). Donor human milk (DHM) is a supplement to mother's own milk, used to support preterm infant nutrition.

OBJECTIVES: We tested whether tissue and plasma β-carotene concentrations would be higher in preterm pigs fed pasteurized DHM versus premature IF.

METHODS: This is a secondary analysis of samples collected from a study of the effects of enteral diet composition on necrotizing enterocolitis incidence. Preterm pigs received partial enteral feeding of either DHM (n …

Ewing's Sarcoma Of The Hand: An Unusual Presentation In A Young Hispanic Male, Dylan B Mcbee, Hope A Bentley, Giancarlo Toledanes

Faculty, Staff and Students Publications

Ewing's sarcoma is a neuroectodermal malignancy classically associated with innocuous and chronic symptomatology. Although tumors typically involve the axial skeleton, some malignancies may be confined to extraosseous tissue only. This report presents the case of a 15-year-old Hispanic male with a tender, slow-growing mass of seven months in the subcutaneous tissue of the right hand. Core needle biopsy and fine needle aspiration confirmed the diagnosis of high-grade extraosseous Ewing's sarcoma and the patient was treated via surgical resection and chemotherapy. Nonspecific findings of Ewing's sarcoma may mimic infection or trauma and contribute to a delay in diagnosis. However, social and …

The Development, Content And Response Process Validation Of A Caregiver-Reported Severity Measure For Cdkl5 Deficiency Disorder, Sonja I Ziniel, Alexandra Mackie, Jacinta Saldaris, Helen Leonard, Peter Jacoby, Eric D Marsh, Bernhard Suter, Elia Pestana-Knight, Heather E Olson, Dana Price, Judith Weisenberg, Rajsekar Rajaraman, Gina Vanderveen, Tim A Benke, Jenny Downs, Scott Demarest

Faculty, Staff and Students Publications

BACKGROUND: CDKL5 Deficiency Disorder (CDD) is a severe X-linked developmental and epileptic encephalopathy. Existing developmental outcome measures have floor effects and cannot capture incremental changes in symptoms. We modified the caregiver portion of a CDD clinical severity assessment (CCSA) and assessed content and response-process validity.

METHODS: We conducted cognitive interviews with 15 parent caregivers of 1-39-year-old children with CDD. Caregivers discussed their understanding and concerns regarding appropriateness of both questions and answer options. Item wording and questionnaire structure were adjusted iteratively to ensure questions were understood as intended.

RESULTS: The CCSA was refined during three rounds of cognitive interviews into …

Multidimensional Biomarker Predicts Disease Control In Response To Immunotherapy In Recurrent Or Metastatic Head And Neck Squamous-Cell Carcinoma, Kevin C Flanagan, Jon Earls, Ian Schillebeeckx, Jeffrey Hiken, Rachel L Wellinghoff, Natalie A Lafranzo, Zachary S Bradley, Joey Babbitt, William H Westra, Raymond Hsu, Lincoln Nadauld, Howard Mcleod, Sean D Firth, Brittany Sharp, Josh Fuller, Vera Vavinskaya, Leisa Sutton, Ida Deichaite, Samuel D Bailey, Vlad C Sandulache, Matthew J Rendo, Orlan K Macdonald, Karim Welaya, James L Wade, Andrew W Pippas, Jennifer Slim, Bruce Bank, Steven J Saccaro, Xingwei Sui, Adil Akhtar, Savitha Balaraman, Steven E Kossman, Scott A Sonnier, Todd D Shenkenberg, Warren L Alexander, Katherine A Price, Charles L Bane, Jessica Ley, David N Messina, Jarret I Glasscock, Ezra E W Cohen, Douglas R Adkins, Eric J Duncavage

Faculty, Staff and Students Publications

PURPOSE: Anti-PD-1 therapy provides clinical benefit in 40-50% of patients with relapsed and/or metastatic head and neck squamous cell carcinoma (RM-HNSCC). Selection of anti- PD-1 therapy is typically based on patient PD-L1 immunohistochemistry (IHC) which has low specificity for predicting disease control. Therefore, there is a critical need for a clinical biomarker that will predict clinical benefit to anti-PD-1 treatment with high specificity.

METHODS: Clinical treatment and outcomes data for 103 RM-HNSCC patients were paired with RNA-sequencing data from formalin-fixed patient samples. Using logistic regression methods, we developed a novel biomarker classifier based on expression patterns in the tumor immune …

Prospective Clinical And Biomarker Validation Of The American Society For Transplantation And Cellular Therapy Consensus Definition For Transplantation-Associated Thrombotic Microangiopathy, Shengling Ma, Saleh Bhar, Danielle Guffey, Rock Bum Kim, Mahrukh Jamil, Christopher I Amos, Stephanie J Lee, Sangeeta R Hingorani, Sarah E Sartain, Ang Li

Faculty, Staff and Students Publications

Transplantation-associated thrombotic microangiography (TA-TMA) is a disorder that causes severe complications after allogeneic hematopoietic cell transplantation (allo-HCT). Diagnosing TA-TMA is challenging because of the lack of standardized criteria. In this study, we aimed to evaluate the new TA-TMA consensus definition from the American Society for Transplantation and Cellular Therapy (ASTCT) panel as part of an ongoing prospective pediatric cohort study, and also to compare the impact and outcomes of using the current definition of clinical TMA (cTMA) versus the new consensus definition. We included patients age 0 to 18 years who underwent their first allo-HCT between May 2021 and January …

Controversies Regarding Management Of Helicobacter Pylori Infections, Alyssa Price, David Y Graham, Mimi C Tan

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: The recognition that Helicobacter pylori should be considered and treated as an infectious disease has yet to fundamentally change diagnostic and treatment practices and has resulted in many controversies.

RECENT FINDINGS: We discuss the following controversies: whether the current 'per-patient' approach to H. pylori testing based on symptoms should be expanded to include achieving population-level H. pylori eradication, whether H. pylori should be approached as an infectious gastrointestinal disease similar to that of other infectious diseases of similar severity and outcome, whether treatment of H. pylori should be primarily empiric or based on antibiotic susceptibility and locally …

The Impact Of Vaccine-Linked Chemotherapy On Liver Health In A Mouse Model Of Chronic Trypanosoma Cruzi Infection, Duc Minh Nguyen, Cristina Poveda, Jeroen Pollet, Fabian Gusovsky, Maria Elena Bottazzi, Peter J Hotez, Kathryn Marie Jones

Faculty, Staff and Students Publications

BACKGROUND: Chagas disease, chronic infection with Trypanosoma cruzi, mainly manifests as cardiac disease. However, the liver is important for both controlling parasite burdens and metabolizing drugs. Notably, high doses of anti-parasitic drug benznidazole (BNZ) causes liver damage. We previously showed that combining low dose BNZ with a prototype therapeutic vaccine is a dose sparing strategy that effectively reduced T. cruzi induced cardiac damage. However, the impact of this treatment on liver health is unknown. Therefore, we evaluated several markers of liver health after treatment with low dose BNZ plus the vaccine therapy in comparison to a curative dose of BNZ. …

Identification Of Factors In Moderate-Severe Tbi Related To A Functional Decline In Cognition Decades After Injury, Christian Lobue, Jeff Schaffert, Kristen Dams-O'Connor, Zinat Taiwo, Angelle Sander, Umesh M Venkatesan, Therese M O'Neil-Pirozzi, Flora M Hammond, Kristin Wilmoth, Kan Ding, Kathleen Bell, C Munro Cullum

Faculty, Staff and Students Publications

OBJECTIVE: To investigate whether a functional decline in cognitive activities decades after moderate-to-severe traumatic brain injury (m-sTBI) might relate to injury features and/or lifetime health factors, some of which may emerge as consequences of the injury.

DESIGN: Secondary analysis of the TBI Model Systems National Database, a prospective, multi-center, longitudinal study of patients with m-sTBI.

SETTING: TBI Model Systems Centers.

PARTICIPANTS: Included were 732 participants rated on the cognitive subscale of the Functional Independence Measure (FIM Cognitive), a metric for everyday cognitive skills, across 3 time points out to 20 years (visits at 2-, 10-, and 20-year follow-ups; N=732).

INTERVENTIONS: …

Pediatric Microsurgery And Free-Tissue Transfer, Heather R Burns, Anna J Skochdopole, Richardo Alfaro Zeledon, William C Pederson

Faculty, Staff and Students Publications

Advancements in microsurgery, along with increased microsurgical experience in pediatric patients, have made free-tissue transfer a reliable modality for pediatric bone and soft tissue reconstruction today. Free-tissue transfer is most commonly used in children for the coverage of large or complex defects resulting from traumatic, oncologic, or congenital etiologies. While flap success and complication rates between pediatric and adult populations are similar, special considerations must be taken into account within the pediatric population. In this article, we will describe common indications, technical nuances, and clinical considerations for the management of the pediatric free-tissue transfer patient.

Cardiac Muscle-Restricted Partial Loss Of Nos1ap Expression Has Limited But Significant Impact On Electrocardiographic Features, Alexa Smith, Dallas Auer, Morgan Johnson, Ernesto Sanchez, Holly Ross, Christopher Ward, Aravinda Chakravarti, Ashish Kapoor

Faculty, Staff and Student Publications

Genome-wide association studies have identified sequence polymorphisms in a functional enhancer of the NOS1AP gene as the most common genetic regulator of QT interval and human cardiac NOS1AP gene expression in the general population. Functional studies based on in vitro overexpression in murine cardiomyocytes and ex vivo knockdown in zebrafish embryonic hearts, by us and others, have also demonstrated that NOS1AP expression levels can alter cellular electrophysiology. Here, to explore the role of NOS1AP in cardiac electrophysiology at an organismal level, we generated and characterized constitutive and heart muscle-restricted Nos1ap knockout mice to assess whether NOS1AP disruption alters the QT …

Circulating Neutrophil-Related Proteins Associate With Incident Heart Failure And Cardiac Dysfunction: The Aric Study, Leo F Buckley, Pranav Dorbala, Brian L Claggett, Peter Libby, Weihong Tang, Josef Coresh, Christie M Ballantyne, Ron C Hoogeveen, Bing Yu, Amil M Shah

Faculty, Staff and Student Publications

AIMS: Neutrophil activity contributes to adverse cardiac remodelling in experimental acute cardiac injury and is modifiable with pharmacologic agents like colchicine.

METHODS AND RESULTS: Neutrophil activity-related plasma proteins known to be affected by colchicine treatment were measured at Visit 3 (1993-1995) and Visit 5 (2011-2013) of the ARIC cohort study. A protein-based neutrophil activity score was derived from 10 candidate proteins using LASSO Cox regression. Associations with incident heart failure (HF) and with cardiac function using Cox proportional hazards regression and linear regression models, respectively. The mean ages at Visits 3 and 5 were 60 ± 6 and 75 ± …