Digital Commons Network^™

Spatial Proteomics Of Onchocerca Volvulus With Pleomorphic Neoplasms Shows Local And Systemic Dysregulation Of Protein Expression, Lucia S. Di Maggio, Kerstin Fischer, Bruce A. Rosa, Devyn Yates, Byoung-Kyu Cho, Jessica Lukowski, Antonia Zamacona Calderon, Minsoo Son, Young Ah Goo, Nicholas O. Opoku, Gary J. Weil, Makedonka Mitreva, Peter U. Fischer

2020-Current year OA Pubs

Onchocerca volvulus is the agent of onchocerciasis (river blindness) and targeted by WHO for elimination though mass drug administration with ivermectin. A small percentage of adult female worms develop pleomorphic neoplasms (PN) which occur more frequently after ivermectin treatment. Worms with PN have a lower life expectancy and improved understanding of proteins expressed in PN and their impact on different tissues could help elucidate the mechanisms of macrofilaricidal activity of ivermectin. Within paraffin embedded nodules removed after ivermectin treatment, we detected 24 (5.6%) O. volvulus females with PN. To assess the protein inventory of the PN and identify proteins potentially …

Transcranial Vibration Stimulation At 40 Hz Induced Neural Activity And Promoted The Coupling Of Global Brain Activity And Cerebrospinal Fluid Flow, Linghan Kong, Wei Jin, Yue Jiang, Fuhua Yan, Jun Liu, Eric C Leuthardt, Guang-Zhong Yang, Yuan Feng

2020-Current year OA Pubs

BACKGROUND: Neuroscience advances have highlighted the potential of non-invasive brain stimulation in influencing cognitive and emotional processes. Conventional stimulation methods such as electrical, magnetic, and ultrasound have been studied intensively, but little is known about the mechanical stimulation.

OBJECTIVE: To investigate the effects of 40 Hz transcranial vibration stimulation (TVS) on human brain activity, specifically focusing on changes in the Amplitude of Low-Frequency Fluctuation (ALFF), fractional ALFF (fALFF) and Regional Homogeneity (ReHo) as measures of spontaneous brain activity. Additionally, this study investigates alterations in the global blood-oxygen-level-dependent (gBOLD) signal and cerebrospinal fluid (CSF) inflow coupling, which serve as indicators of …

Effect Of Midwife-Led Pelvic Floor Muscle Training On Prolapse Symptoms And Quality Of Life In Women With Pelvic Organ Prolapse In Ethiopia: A Cluster-Randomized Controlled Trial, Melese Siyoum, Rahel Nardos, Biniyam Sirak, Theresa Spitznagle, Wondwosen Teklesilasie, Ayalew Astatkie

2020-Current year OA Pubs

BACKGROUND: Pelvic organ prolapse (POP) is a common condition that can significantly impact a woman's quality of life. Pelvic floor muscle training (PFMT) is recommended as a first-line conservative treatment for prolapse, but evidence on its effectiveness from low-resource settings is limited. This study aimed to assess the effect of midwife-led PFMT on prolapse symptoms and health-related quality of life (HRQoL) among women with mild-to-moderate POP in Ethiopia.

METHODS AND FINDINGS: A community-based, parallel-groups, two-arm cluster-randomized controlled trial was conducted in Dale and Wonsho districts of Sidama Region, Ethiopia. Women with symptomatic POP stages I-III were randomized by cluster to …

Upper Cervical Spinal Cord Atrophy In Ms: Sex, Menopause, And Neurodegeneration, Burcu Zeydan, Jiye Son, Nur Neyal, Christopher G Schwarz, Elizabeth J Atkinson, Holly A Morrison, Nabeela Nathoo, Kejal Kantarci, Eoin P Flanagan, John D Port, Orhun H Kantarci

Faculty, Staff and Students Publications

Background: Spinal cord (SC) atrophy is a key imaging biomarker of progressive multiple sclerosis (MS). Progressive MS is more common in men and postmenopausal women.

Objective: Investigate the impact of sex and menopause on SC measurements in persons with MS (pwMS).

Methods: In pwMS and age- and sex-matched controls, upper cervical SC area from brain MRI (UCCbrain) was obtained. Impact of sex and menopause on UCCbrain (adjusted for total intracranial volume) and its association with progression and disability, including MS functional composite (MSFC), were investigated.

Results: UCCbrain was smaller in pwMS (n = 118, 51.4 ± 5.3 mm2) than …

Immunogenetic Studies In Patients With Gad-Positive Stiff-Person Syndrome Reveal Novel Lymphocytic Genes And Klk10 -Gene Variants, Popianna Tsiortou, Harry Alexopoulos, Konstantinos Kyriakidis, Michalis Kosmidis, Chrysanthi Barba, Sofia Akrivou, Ioannis Michalopoulos, Panagiotis Politis, Marinos Dalakas

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: The aim of this study was to identify genetic markers and immunologic characteristics of glutamic acid decarboxylase (GAD) antibody-positive patients with stiff-person syndrome (SPS).

METHODS: We conducted systemic immunogenetic studies in 11 GAD-positive patients: 8 with sporadic SPS and 3 from a three-generation family with very high GAD-ab titers but diverse symptomatology (one with GAD-epilepsy and SPS and 2 only with diabetes), by performing complete immunologic profile and whole-exome sequencing analysis.

RESULTS: Two genes expressed in immune and neuronal tissues were identified: the ORAI1 that codes for a calcium release–activated channel protein with a role in the …

Care Utilization For Acute Respiratory Infections In Children Requiring Invasive Long-Term Mechanical Ventilation, Carolyn C Foster, Todd A Florin, Derek J Williams, Katherine L Freundlich, Rebecca L Steuart, Julia A Heneghan, Cara Cecil, Nathan M Pajor, Robert J Graham, Sriram Ramgopal

Faculty, Staff and Student Publications

Introduction: Children who use invasive long-term mechanical ventilation (LTMV) are a rare, clinically heterogenous population with relatively high hospitalization rates, most commonly for acute respiratory infection (ARI). We sought to describe patterns of ARI-related utilization and mortality in pediatric patients with LTMV, evaluating the association of a pre-existing neurologic diagnoses with outcomes.

Methods: We studied a longitudinal retrospective cohort across 40 U.S. children's hospital emergency department (ED) and hospital encounters for patients (< 21 years) with LTMV and an ARI diagnosis code (10/1/2016-6/30/2023). We examined mortality and ED/hospital utilization outcomes, defining short-stay hospitalizations as ≤ 2 calendar days. We stratified analyses by high intensity neurologic impairment (HINI) using a validated coding algorithm.

Results: We included 4866 patients (median age 4.5 years; 58.6% male) with LTMV and ≥ 1 ARI encounter. Most (95.1%) were hospitalized on their index encounter, and …

Pharmacodynamics Of Aspirin Through Gestation: Predictors Of Aspirin Response And Association With Pregnancy Outcome, A Prospective Cohort Study, Rupsa C. Boelig, Emily Foecke Munden, Tingting Zhan, Steven E. Mckenzie, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Low-dose aspirin is recommended for prevention of hypertensive disorders of pregnancy (HDP) and preterm birth (PTB) in high-risk pregnancies. There is limited data on factors impacting aspirin response in pregnancy. We aimed to evaluate predictors of aspirin response and association with pregnancy outcome with a prospective study of high-risk pregnancies taking 81 mg aspirin daily. Aspirin response was evaluated with Platelet Function Assay-100 (PFA-100) epinephrine closure time at baseline (< 16 weeks' gestation), follow-up 1 (2-4 weeks after aspirin initiation), and follow-up 2 (28-32 weeks gestation). Multivariable regression was used to identify factors associated with PFA-100 at each visit, and results presented with beta coefficient (B) and confidence interval. The median difference (MD) in PFA-100 in those with and without HDP or PTB was compared. Results included 108 who completed follow-up 1 and 96 who completed both visits with > 75% adherence. PFA-100 was increased from baseline at follow-ups 1 and 2 (MD 37 (27-49); MD 26 (15.5-38.5) respectively). At follow-up 1, obesity (B = -30 (-53 to -7) seconds), …

Training Protocol And Calibration Of The International Caries Detection And Assessment System In A School-Based Clinical Trial Of Elementary School-Age Children, Jose-Miguel Yamal, Dania Mofleh, Ru-Jye Chuang, Mengxi Wang, Kila Johnson, Alejandra Garcia-Quintana, Tolulope Titiloye, Suchitra Nelson, Shreela V Sharma

Faculty, Staff and Student Publications

Objectives: This paper demonstrates International Caries Detection and Assessment System (ICDAS) training procedures and inter/intra-examiner reliability for lesion severity, activity, and filling criteria in an elementary school setting.

Methods: ICDAS training was conducted in December 2021 prior to a school-based cluster-randomized controlled trial. A total of 59 children (6-8 years old) in grades 1-2 from one school in Houston, Texas were recruited. Two licensed dentists received a 5-day training from an ICDAS trainer at the participating school. Thirty-eight children were evaluated at least once by each dental trainee, and 18 had repeat examinations. The ICDAS criteria were used to classify …

Predicting Fatal Opioid-Involved Overdoses: A Social-Ecological Framework Matched To A Linked-Data Warehouse, Ric Bayly, Jack Cordes, Dana Bernson, Leland K Ackerson, Marc R Larochelle, Ghada H Hassan, Cici X Bauer, Thomas J Stopka

Faculty, Staff and Student Publications

Background: An estimated 60 million people used opioids non-medically worldwide in 2021. In 2019, opioid use disorder caused the loss of over 12.5 million healthy years of life due to disability and premature deaths, including those resulting from opioid-involved overdoses. Factors associated with opioid-involved overdoses are numerous, multi-layered, and interrelated. Using the social-ecological model as a foundation, we sought to comprehensively identify risk and preventive factors of fatal opioid-involved overdoses and operationalize them with quantifiable measures.

Methods: With our Community Advisory Board, investigators' expertise, and an examination of the literature, we created an expansive, opioid-overdose specific social-ecological model structured as …

Risk Of Traumatic Brain Injury In Deployment And Nondeployment Settings Among Members Of The Millennium Cohort Study, Kalyn C Jannace, Lisa Pompeii, David Gimeno Ruiz De Porras, William Brett Perkison, Jose-Miguel Yamal, Daniel W Trone, Rudolph P Rull

Faculty, Staff and Student Publications

Objective: To describe and quantify the prevalence and risk of deployment and nondeployment service-related traumatic brain injury (TBI) among participants of the Millennium Cohort Study.

Setting: Survey data.

Participants: 28 759 Millennium Cohort Study participants who were active duty, Reserves, or National Guard at the time of the survey.

Design: Cross-sectional secondary data analysis.

Main measures: Estimates of prevalence and rates of TBI were calculated. Multivariable Poisson regression estimated rate ratios of TBI overall and stratified by deployment and nondeployment settings.

Results: The rate of TBI over the 362 535 person-years (PY) was 2.95 p/100 PY. the nondeployment rate was …

An Adaptive Antiretroviral Therapy Adherence Intervention For Youth With Hiv Through Text Message And Cell Phone Support With And Without Incentives: A Sequential Multiple Assignment Randomized Trial (Smart), Marvin E Belzer, Karen Macdonell, Demetria Cain, Samiran Ghosh, Richard Zhao, Julie Mcavoy-Banerjea, Sitaji Gurung, Sylvie Naar

Faculty, Staff and Student Publications

Youth living with HIV have low rates of medication adherence. Youth ages 15-24 years with adherence ≤ 80% or with HIV RNA PCRs (VL) ≥ 200 recruited through social media and clinical sites were randomized to brief weekday cell phone support (CPS) calls or daily, two-way, personalized text message (SMS) reminders for 3 months. Those with VL ≥ 200 or adherence ≤ 80% were rerandomized to receive SMS or CPS with monthly incentives for those utilizing the intervention at least 75% of days for 3 months. Those with VL < 200 or adherence > 80% after the initial 3 months were rerandomized to usual care …

Sacubitril/Valsartan Attenuates Inflammation And Myocardial Fibrosis In Takotsubo-Like Cardiomyopathy, Jiangying Kuang, Zhiyi Jia, Tou Kun Chong, Jian Chen, Kan Liu, Xin Wang, Zhaohua Li, Jing Zhang, Yanru Kong, Lin Deng, Martin Cadieras, Yuanyuan Sun, Rong Sun, Qinghua Lu, Yusheng Liu

2020-Current year OA Pubs

BACKGROUND: Takotsubo syndrome (TTS) primarily manifests as a cardiomyopathy induced by physical or emotional stress, remains a poorly understood condition with no established treatments. In this study, we investigated the potential of sacubitril/valsartan (sac/val) to increase the survival of TTS patients and reduce inflammation and myocardial fibrosis in experimental models.

AIM: This study aimed to evaluate whether sac/val could improve survival rates in TTS patients, mitigate cardiac remodeling in vivo, and explore its anti-inflammatory and antifibrotic mechanisms in vitro.

METHODS: Clinical cases from the Chinese Takotsubo syndrome (ChiTTS) registry were analyzed to assess patient survival rates. In addition, we used …

Regional Lung Ventilation During Supraglottic And Subglottic Jet Ventilation: A Randomized Cross-Over Trial, Marita Windpassinger, Michal Prusak, Jana Gemeiner, Maximilian Edlinger-Stanger, Imme Roesner, Doris-Maria Denk-Linnert, Olga Plattner, Ahmed Khattab, Eugenijus Kaniusas, Lu Wang, Daniel I Sessler

Faculty, Staff and Student Publications

Objective: Test the hypothesis that the center of ventilation, a measure of ventro-dorsal atelectasis, is posterior during supraglottic ventilation indicating better dependent-lung ventilation. Secondarily, we tested the hypothesis that supraglottic ventilation improves oxygenation and carbon dioxide elimination.

Background: Supraglottic and subglottic jet ventilation are both used during laryngotracheal surgery. Supraglottic jet ventilation may better prevent atelectasis and provide superior ventilation.

Design: Randomized, cross-over trial.

Setting: Operating rooms.

Patients: Patients having elective micro-laryngotracheal surgery.

Interventions: Patients were sequentially ventilated for 5 min with one randomly selected type of jet ventilation before being switched to the alternative method.

Measurements: Regional ventilation distribution …

Association Of The Child Opportunity Index On Severity Of Pediatric Asthma Exacerbation Admissions, Magda Haj, Daniel L Brinton, Elizabeth Oddo, Daniel Williams, Ronald J Teufel Ii

Faculty, Staff and Student Publications

Background: Asthma is one of the most common chronic childhood diseases and reason for hospital admission. Previous studies using Childhood Opportunity Index (COI), a 5-level scale assessing neighborhood opportunity, have demonstrated mixed associations with asthma admissions and less often considered a child's initial presentation to a children's hospital.

Objective: Among children presenting to the emergency department (ED), explore the association of COI with asthma admission and admission severity.

Methods: This was a retrospective study using the Pediatric Health Information System database including patients aged 2 to 18 years presenting to the ED for asthma exacerbations from May 1, 2022, to …

Early Achievement Of Hemostasis Defined By Transfusion Velocity: A Possible Mechanism For Whole Blood Survival Benefit, Amanda M Chipman, James F Luther, Francis X Guyette, Bryan A Cotton, Jeremy W Cannon, Martin A Schreiber, Ernest E Moore, Nicholas Namias, Joseph P Minei, Mark H Yazer, Laura Vincent, Abigail L Cotton, Vikas Agarwal, Joshua B Brown, Christine M Leeper, Matthew D Neal, Raquel M Forsythe, Stephen R Wisniewski, Jason L Sperry, Swat Study Group

Faculty, Staff and Student Publications

Introduction: Whole blood resuscitation is associated with survival benefits in observational cohort studies. The mechanisms responsible for outcome benefits have not been adequately determined. We sought to characterize the achievement of hemostasis across patients receiving early whole blood versus component resuscitation. We hypothesized that achieving hemostasis would be associated with outcome benefits and patients receiving whole blood would be more likely to achieve hemostasis.

Methods: We performed a post hoc retrospective secondary analysis of data from a recent prospective observational cohort study comparing early whole blood and component resuscitation in patients at risk of hemorrhagic shock. Achievement of hemostasis was …

The Associations Of Sensory Impairment With 10-Year Risk Of Dementia And Alzheimer's Disease: The Health And Retirement Study, 2010-2020, Kun Li, Rahul Ghosal, Donglan Zhang, Yike Li, Matthew C Lohman, Monique J Brown, Anwar T Merchant, Chih-Hsiang Yang, Jean Neils-Strunjas, Daniela B Friedman, Jingkai Wei

Faculty, Staff and Student Publications

Background: Studies have examined the association between dual sensory impairment and late-life cognitive outcomes in the U.S with inconsistent findings.

Objective: To examine the associations between sensory impairment and 10-year risk of dementia or Alzheimer's disease among U.S. adults aged ≥ 50.

Methods: A prospective cohort study based on the Health and Retirement Study from 2010 to 2020. Individuals aged ≥ 50 years without self-reported dementia and Alzheimer's disease in 2010 were included in the analysis. Self-reported visual and hearing impairments were measures in 2010. Main failure events included self-reported incident dementia and Alzheimer's disease over a 10-year follow-up period. …

Nulliparous With Class Iii Obesity At Term: Labor Induction Or Cesarean Delivery Without Labor, Yossi Bart, Rachel L Wiley, Ipsita Ghose, Michal Fishel Bartal, Khalil M Chahine, Suneet P Chauhan, Sean Blackwell, Baha M Sibai

Faculty, Staff and Student Publications

Objective: This study aimed to compare maternal and neonatal outcomes between labor induction versus cesarean delivery (CD) without labor among nulliparous individuals with class III obesity (body mass index [BMI] ≥40 kg/m2).

Study design: A retrospective cohort study of all nulliparous singleton deliveries at ≥37 weeks with a BMI of ≥40 kg/m2 at delivery between March 2020 and February 2022. We excluded individuals with spontaneous labor, fetal malformations, and stillbirths. The primary outcome was a composite of maternal mortality and morbidity, including infectious and hemorrhagic morbidity. The secondary outcome was a neonatal composite. A subgroup analysis evaluated patients with a …

Intra- And Postoperative Complications In 4565 Vnotes Hysterectomies: International Registry Cohort Study., Andrea Stuart, Johanna Wagenius, Levon Badiglian-Filho, Jens Schnabel, Alvaro Montealegre, Sophia Ehrström, Michael Hartmann, Jona Vercammen, Daniela Huber, Anna Lingström, Jan Baekelandt

Faculty, Staff and Student Publications

Objective: To present the rates of intra- and postoperative complications and conversions in a large cohort of unselected vNOTES hysterectomies, performed by surgeons with different levels of expertise.

Design: International register-based cohort study.

Setting: Hysterectomies in the iNOTESs registry, 2015 to January 2024, performed by 201 surgeons from multiple countries.

Population: 4565 patients undergoing vNOTES hysterectomy.

Methods: Descriptive data are presented in frequencies (n) and percent (%).

Main outcome measure: Intra- and postoperative complications. Conversions.

Results: Intraoperative and postoperative complication rates were 3.2% (n = 144) and 2.5% (n = 115), respectively. Conversions occurred in 1.6% (n = 72), of …

Liver Involvement In A Large Cohort Of Patients With Erythropoietic Protoporphyria Or X-Linked Protoporphyria, Cynthia Levy, Hetanshi Naik, Jessica Overbey, Karli Hedstrom, Kelly Wang, Catherine Mcdonough, Mary Freeman, Siobán B Keel, Angelika L Erwin, Amy K Dickey, Rebecca K Leaf, John Quigley, Marshall Mazepa, Bruce Wang, John Phillips, Charles Parker, Brendan Mcguire, Mohamed Kazamel, Herbert Bonkovsky, Sean Rudnick, Karl E Anderson, Akshata Moghe, Manish Thapar, Behnam Saberi, Kristen Wheeden, Robert Desnick, Manisha Balwani, Porphyrias Consortium Of The Rare Diseases Clinical Research Network

Faculty, Staff and Student Publications

Background: Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are characterized by the accumulation of protoporphyrin in the marrow, erythrocytes, plasma, skin, and liver, and present clinically with painful cutaneous phototoxicity. Liver abnormalities have been reported in over 25% of patients with EPP. Further characterization of liver involvement in protoporphyria is needed.

Methods: Patients with EPP or XLP enrolled in the longitudinal studies of the NIH-supported Porphyrias Consortium were included. Medical history, laboratory, and liver histology data were abstracted and described.

Results: A total of 322 patients were enrolled; 28 (8.7%) had XLP, 52% were female, and the median age at …

Assessment Of Skin Fibrosis In A Murine Model Of Systemic Sclerosis With Multifunctional Optical Coherence Tomography, Harshdeep Singh Chawla, Yanping Chen, Minghua Wu, Pavel Nikitin, Jessica Gutierrez, Chandra Mohan, Manmohan Singh, Salavat R Aglyamov, Shervin Assassi, Kirill V Larin

Faculty, Staff and Student Publications

Significance: Systemic sclerosis (SSc) is a chronic idiopathic disease that causes immune dysregulation, vasculopathy, and organ fibrosis that affects more than 3 million people in the US alone. The modified Rodnan skin score (mRSS) is the current gold standard for diagnosing and staging skin fibrosis in SSc. However, mRSS is subjective, requires extensive training, and has high observer variability.

Aim: We aim to provide a quantitative method for the assessment of fibrosis.

Approach: We utilized optical coherence tomography (OCT), its extensions, optical coherence elastography (OCE), and OCT angiography (OCTA) to evaluate SSc-like fibrosis and therapy response in a mouse model. …

[Treatment Adherence For Attention Deficit Hyperactivity Disorder (Adhd) In The Champ Ut-Health Houston Program], Rachitha P Jadala, Hali Temkin, Kerri L Daniel, Cesar A Soutullo

Faculty, Staff and Student Publications

Introduction: ADHD has a safe and effective treatment, but treatment adherence is often low. Several factors contribute to this low adherence, some of which are modifiable.

Methods: We conducted a literature review of recent studies on medication adherence in children and adolescents with ADHD. We gathered data on ADHD treatment adherence from our clinic in the ADHD Program and the Child and Adolescent Mood Disorders Program (ChAMP) at the University of Texas Health-Houston Program. We analyzed factors related to medication adherence, such as patient age, sex, prescription type, release formula, and their association with adherence in 117 patients with ADHD …

The Changing Faces Of Academic Family Medicine Leadership: A Cera Secondary Analysis., Bryce A Ringwald, Yasamine Edwards, Sarah Vengal, Jon Montemayor, Carter Ringwald

Medical Education Articles

BACKGROUND AND OBJECTIVES: Diversity, equity, and inclusion (DEI) efforts strive to create a physician workforce that represents the general population. Barriers remain, however, regarding the promotion of women and underrepresented in medicine (URiM) physicians. We sought to describe gender and race trends in academic family medicine leadership over the past decade.

METHODS: We performed a secondary analysis of Council of Academic Family Medicine Educational Research Alliance clearinghouse data, examining demographic survey responses from available surveys of family medicine clerkship directors (CDs), program directors (PDs), and department chairs from 2011 to 2023.

RESULTS: During the time studied, family medicine CDs female …

Predicting Chemotherapy Responsiveness In Gastric Cancer Through Machine Learning Analysis Of Genome, Immune, And Neutrophil Signatures, Shota Sasagawa, Yoshitaka Honma, Xinxin Peng, Kazuhiro Maejima, Koji Nagaoka, Yukari Kobayashi, Ayako Oosawa, Todd A Johnson, Yuki Okawa, Han Liang, Kazuhiro Kakimi, Yasuhide Yamada, Hidewaki Nakagawa

Faculty, Staff and Student Publications

Background: Gastric cancer is a major oncological challenge, ranking highly among causes of cancer-related mortality worldwide. This study was initiated to address the variability in patient responses to combination chemotherapy, highlighting the need for personalized treatment strategies based on genomic data.

Methods: We analyzed whole-genome and RNA sequences from biopsy specimens of 65 advanced gastric cancer patients before their chemotherapy treatment. Using machine learning techniques, we developed a model with 123 omics features, such as immune signatures and copy number variations, to predict their chemotherapy outcomes.

Results: The model demonstrated a prediction accuracy of 70-80% in forecasting chemotherapy responses in …

A Neoantigen Vaccine Generates Antitumour Immunity In Renal Cell Carcinoma, David A Braun, Giorgia Moranzoni, Vipheaviny Chea, Bradley A Mcgregor, Eryn Blass, Chloe R Tu, Allison P Vanasse, Cleo Forman, Juliet Forman, Alexander B Afeyan, Nicholas R Schindler, Yiwen Liu, Shuqiang Li, Jackson Southard, Steven L Chang, Michelle S Hirsch, Nicole R Leboeuf, Oriol Olive, Ambica Mehndiratta, Haley Greenslade, Keerthi Shetty, Susan Klaeger, Siranush Sarkizova, Christina B Pedersen, Matthew Mossanen, Isabel Carulli, Anna Tarren, Joseph Duke-Cohan, Alexis A Howard, J Bryan Iorgulescu, Bohoon Shim, Jeremy M Simon, Sabina Signoretti, Jon C Aster, Liudmila Elagina, Steven A Carr, Ignaty Leshchiner, Gad Getz, Stacey Gabriel, Nir Hacohen, Lars R Olsen, Giacomo Oliveira, Donna S Neuberg, Kenneth J Livak, Sachet A Shukla, Edward F Fritsch, Catherine J Wu, Derin B Keskin, Patrick A Ott, Toni K Choueiri

Faculty, Staff and Student Publications

Personalized cancer vaccines (PCVs) can generate circulating immune responses against predicted neoantigens1-6. However, whether such responses can target cancer driver mutations, lead to immune recognition of a patient's tumour and result in clinical activity are largely unknown. These questions are of particular interest for patients who have tumours with a low mutational burden. Here we conducted a phase I trial (ClinicalTrials.gov identifier NCT02950766) to test a neoantigen-targeting PCV in patients with high-risk, fully resected clear cell renal cell carcinoma (RCC; stage III or IV) with or without ipilimumab administered adjacent to the vaccine. At a median follow-up of 40.2 …

Wmh Contributions To Cognitive Impairment: Rationale And Design Of The Diverse Vcid Study, Charles Decarli, Kumar B Rajan, Lee-Way Jin, Jason Hinman, David K Johnson, Danielle Harvey, Myriam Fornage

Faculty, Staff and Student Publications

As awareness of dementia increases, more individuals with minor cognitive complaints are requesting clinical assessment. Neuroimaging studies frequently identify incidental white matter hyperintensities, raising patient concerns about their brain health and future risk for dementia. Moreover, current US demographics indicate that ≈50% of these individuals will be from diverse backgrounds by 2060. Racial and ethnic minority populations bear a disproportionate burden of vascular risk factors magnifying dementia risk. Despite established associations between white matter hyperintensities and cognitive impairment, including dementia, no study has comprehensively and prospectively examined the impact of individual and combined magnetic resonance imaging measures of white matter …

Genetic Characterization Of A Large Cohort Of Individuals With A Clinical Suspicion Of Hypophosphatasia In The United States., Eric T. Rush, Guillermo Del Angel, Juan Dong, Toby Bates, Robert D. Steiner, Allison Cox

Manuscripts, Articles, Book Chapters and Other Papers

Hypophosphatasia (HPP) is a rare metabolic disease resulting from variants in ALPL, inherited in an either autosomal recessive or autosomal dominant manner. Sponsored clinical ALPL testing was offered in the US for individuals with a clinical suspicion of HPP. Gene variants were assessed to determine the likelihood of identifying disease-causing variants, uncover genotype-phenotype relationships, and for further understanding of ALPL variants in the US HPP population. Variants were detected by Sanger sequencing and classified as pathogenic or likely pathogenic (P/LP; positive test result), variant(s) of uncertain significance (indeterminate test result), benign or likely benign (negative test result), or no variants …

Early Life Epigenetics And Childhood Outcomes: A Scoping Review, Srirupa Hari Gopal, Theresa Alenghat, Mohan Pammi

Faculty, Staff and Students Publications

Epigenetics is the study of changes in gene expression, without a change in the DNA sequence that are potentially heritable. Epigenetic mechanisms such as DNA methylation, histone modifications, and small non-coding RNA (sncRNA) changes have been studied in various childhood disorders. Causal links to maternal health and toxin exposures can introduce epigenetic modifications to the fetal DNA, which can be detected in the cord blood. Cord blood epigenetic modifications provide evidence of in-utero stressors and immediate postnatal changes, which can impact both short and long-term outcomes in children. The mechanisms of these epigenetic changes can be leveraged for prevention, early …

Epstein-Barr Virus Sequence Variations Among The Understudied Nasopharyngeal Carcinoma Patients Of Diverse Ancestries In Southeast Asia, Hwee Sze Tee, Jingtong Liang, Norazlin Abdul Aziz, Xiang Zhou, Hamidah Akmal Hisham, Ke-En Tan, Yanhong Chen, Zuriani Burhanuddin, Johnny S.H. Kwan, Kwok-Wai Lo, Faridah Hassan, Sha'ariyah Bt Mohd Mokhtar, Alan Soo Beng Khoo, Miao Xu, Yat-Yuen Lim, Lu Ping Tan

Department of Medical Oncology Faculty Papers

Epstein-Barr virus (EBV) is associated with cancers, including lymphomas and nasopharyngeal carcinoma (NPC). To date, risk variants for NPC were mainly identified from Chinese populations, which dominated the world's total number of cases. Although Southeast Asia (SEA) countries have among the world's top yet intriguingly diverse NPC age-standardized incidence rates across subpopulations, data on EBV from SEA remains scarce. In this study, we examined 83 NPC patients of different ancestries for the presence of risk haplotypes associated with the Southern Chinese NPC and generated and analyzed 67 EBV sequences (from tissue, patient-derived xenografts and lymphoblastoid cell lines of 60 NPC …

Prevention And Management Of Infectious Complications In Pediatric Patients With Cancer: A Survey Assessment Of Current Practices Across Children's Oncology Group Institutions., Leonora R. Slatnick, David Hoogstra, Brian T. Fisher, Joshua Wolf, Etan Orgel, C Nathan Nessle, Pratik A. Patel, Tamara P. Miller, Jennifer Wilkes, L Lee Dupuis, Erin Goode, Kasey Jackson, Daniel N. Willis, Caitlin Elgarten, Catherine Aftandilian, Joel Thompson, Sarah Alexander, Melissa P. Beauchemin, Jennifer A. Belsky, Jennifer Hess, Zachary D. Prudowsky, Terri Guinipero, Jenna Rossoff, Jenna Demedis, Alexandra M. Walsh, Rebecca Richards, Daniel K. Choi, Christopher C. Dvorak, Adam J. Esbenshade

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: While clinical practice guidelines (CPGs) for pediatric oncology infection prophylaxis and management exist, few data describe actual management occurring at pediatric oncology centers.

METHODS: An electronic survey querying infection management practices in nontransplant pediatric oncology patients was iteratively created by the Children's Oncology Group (COG) Cancer Control and Supportive Care Infectious Diseases Subcommittee and sent to leaders at all COG institutions, limiting each site to one response to represent their institution.

RESULTS: The response rate was 57% (129/227 institutions). Many sites reported utilizing COG-endorsed CPGs for antibacterial (76%) and antifungal prophylaxis (74%), and fever and neutropenia (FN, 64%). Most …

Cervical Necrotizing Fasciitis And Shock In The Post-Operative Pediatric Patient., Paul Bryan Hankey, Jason R. Brown

Manuscripts, Articles, Book Chapters and Other Papers

Cervical necrotizing fasciitis (CNF) is a rare infection that can quickly lead to devastating patient outcomes. Considering the vital importance of surrounding neck structures, rapid control of the infection is essential. Infection is most frequently polymicrobial and occurs in the adult patient in the context of certain medical comorbidities. Complications are typically limited to tissue destruction in the form of necrosis. There are no current reports describing CNF complicated by acute shock in the post-operative pediatric patient. Here, we present a pediatric case of CNF complicated by acute shock following Sistrunk procedure for removal of a supposed thyroglossal duct cyst. …