Digital Commons Network^™

Unilateral Radiation Therapy For Tonsillar Cancer: Treatment Outcomes In The Era Of Human Papillomavirus, Positron-Emission Tomography, And Intensity Modulated Radiation Therapy, Nicolette Taku, Gregory Chronowski, G Brandon Gunn, William H Morrison, Neil D Gross, Amy C Moreno, Renata Ferrarotto, Steven J Frank, C David Fuller, Ryan P Goepfert, Jack Phan, Stephen Y Lai, Jay P Reddy, David I Rosenthal, Adam S Garden

Faculty, Staff and Student Publications

Purpose: The goal of this study was to evaluate disease, survival, and toxic effects after unilateral radiation therapy treatment for tonsillar cancer.

Methods and materials: A retrospective study was performed of patients treated at our institution within the period from 2000 to 2018. Summary statistics were used to assess the cohort by patient characteristics and treatments delivered. The Kaplan-Meier method was used to determine survival outcomes.

Results: The cohort comprised 403 patients, including 343 (85%) with clinical and/or radiographic evidence of ipsilateral cervical nodal disease and 181 (45%) with multiple involved nodes. Human papillomavirus was detected in 294 (73%) tumors. …

Insulin Resistance In Depression: A Large Meta-Analysis Of Metabolic Parameters And Variation, Brisa S Fernandes, Estela Salagre, Nitesh Enduru, Iria Grande, Eduard Vieta, Zhongming Zhao

Faculty, Staff and Student Publications

Increased insulin resistance is recognized in psychiatric disorders, such as schizophrenia and bipolar disorder, but its occurrence in depression is less clear. Our aims were to verify if insulin resistance is altered in depression, to test the metabolic subgroup hypothesis of depression and if there are changes with antidepressants. Inclusion criteria were studies including adult subjects with depression and either a control group or follow-up after treatment with antidepressants, and assessing fasting insulin or glucose levels or the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index. Seventy studies with 240,704 participants were included. Both insulin levels and the HOMA-IR index …

The Geriatric Nutritional Risk Index As A Predictor Of Complications In Geriatric Trauma Patients: Author Reply In Response To: “The Admission Serum Level Of Albumin Cannot Thoroughly Represent The Nutritional Status Of Trauma Patients”, Heather R Kregel, Patrick B Murphy, Mina Attia, David E Meyer, Rachel S Morris, Ezenwa C Onyema, Sasha D Adams, Charles E Wade, John A Harvin, Lillian S Kao, Thaddeus J Puzio

Faculty, Staff and Student Publications

BACKGROUND: Malnutrition is associated with increased morbidity and mortality after trauma. The Geriatric Nutritional Risk Index (GNRI) is a validated scoring system used to predict the risk of complications related to malnutrition in nontrauma patients. We hypothesized that GNRI is predictive of worse outcomes in geriatric trauma patients.

METHODS: This was a single-center retrospective study of trauma patients 65 years or older admitted in 2019. Geriatric Nutritional Risk Index was calculated based on admission albumin level and ratio of actual body weight to ideal body weight. Groups were defined as major risk (GNRI98). The primary outcome was mortality. Secondary outcomes …

Strategy For Generating Blinded Evidence For Single-Arm Trials With External Controls Using Expert Review Of Home Video, Bharti Manwani, Carson Finger, Lynda Lisabeth

Faculty, Staff and Student Publications

Stroke risk and prevalence increase with advanced age and women tend to be older than men at the time of their first stroke. Advanced age in women confers unique stroke risks that are beyond reproductive factors. Previous reviews and guidelines have largely focused on risk factors specific to women, with a predominant focus on reproductive factors and, therefore, younger to middle-aged women. This review aims to specifically describe stroke risk factors in elderly women, the population of women where the majority of strokes occur, with a focus on atrial fibrillation, hormone therapy, psychosocial risk factors, and cognitive impairment. Our review …

Randomized Placebo-Controlled Trial Of Losartan For Pediatric Nafld, Miriam B Vos, Mark L Van Natta, Niviann M Blondet, Srinivasan Dasarathy, Mark Fishbein, Paula Hertel, Ajay K Jain, Saul J Karpen, Joel E Lavine, Saeed Mohammad, Laura A Miriel, Jean P Molleston, Marialena Mouzaki, Arun Sanyal, Emily P Sharkey, Jeffrey B Schwimmer, James Tonascia, Laura A Wilson, Stavra A Xanthakos, Nash Clinical Research Network

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects.

APPROACH AND RESULTS: The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double-masked, placebo-controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020). Inclusion criteria were age 8-17 years, histologic NAFLD activity score ≥ 3, and serum alanine aminotransferase (ALT) ≥ 50 U/l. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT …

Salivary Biomarker Evaluation Of Chronic Pancreatitis Patients Reveals Alterations In Human Proteins, Cytokines, Prostaglandin E2 Levels, And Bacterial Diversity, Richard T Waldron, Elaina K Jones, Vincent I Anani, Jolaine M Hines, Jing Zhao, Aurelia Lugea, Marcio A Diniz, Sungjin Kim, Aida Habtezion, Kristi L Hoffman, Joseph F Petrosino, William E Fisher, Liang Li, Ryan J Lennon, Ravinder Jit Singh, Santhi Swaroop Vege, Stephen J Pandol, Mark D Topazian

Faculty, Staff and Students Publications

OBJECTIVES: Chronic pancreatitis (CP) is a chronic fibroinflammatory condition of the pancreas difficult to diagnose in early stages. Novel biomarkers useful to facilitate early diagnosis or treatment responses may be found in biofluids. Although saliva can be easily and noninvasively collected from patients, useful salivary biomarkers from CP patients have not yet been identified.

METHODS: Here, we analyzed the proteome by quantitative proteomics, cytokine/chemokine levels by Luminex analysis, prostaglandin E2 (PGE2) levels by a mass spectrometry-based assay, and bacterial species diversity by 16S ribosomal ribonucleic acid sequencing in saliva samples from confirmed CP patients and healthy controls.

RESULTS: Our results …

Fetal Loss In Pregnant Rhesus Macaques Infected With High-Dose African-Lineage Zika Virus, Lauren E. Raasch, Kevin K. Noguchi, Nicole A. Fuhler, Et Al

2020-Current year OA Pubs

Countermeasures against Zika virus (ZIKV), including vaccines, are frequently tested in nonhuman primates (NHP). Macaque models are important for understanding how ZIKV infections impact human pregnancy due to similarities in placental development. The lack of consistent adverse pregnancy outcomes in ZIKV-affected pregnancies poses a challenge in macaque studies where group sizes are often small (4-8 animals). Studies in small animal models suggest that African-lineage Zika viruses can cause more frequent and severe fetal outcomes. No adverse outcomes were observed in macaques exposed to 1x104 PFU (low dose) of African-lineage ZIKV at gestational day (GD) 45. Here, we exposed eight pregnant …

Adipose Tissue-Specific Ablation Of Ces1d Causes Metabolic Dysregulation In Mice, Gang Li, Xin Li, Li Yang, Shuyue Wang, Yulin Dai, Baharan Fekry, Lucas Veillon, Lin Tan, Rebecca Berdeaux, Kristin Eckel-Mahan, Philip L Lorenzi, Zhongming Zhao, Richard Lehner, Kai Sun

Faculty, Staff and Student Publications

Carboxylesterase 1d (Ces1d) is a crucial enzyme with a wide range of activities in multiple tissues. It has been reported to localize predominantly in ER. Here, we found that Ces1d levels are significantly increased in obese patients with type 2 diabetes. Intriguingly, a high level of Ces1d translocates onto lipid droplets where it digests the lipids to produce a unique set of fatty acids. We further revealed that adipose tissue-specific Ces1d knock-out (FKO) mice gained more body weight with increased fat mass during a high fat-diet challenge. The FKO mice exhibited impaired glucose and lipid metabolism and developed exacerbated liver …

Expanding Acta2 Genotypes With Corresponding Phenotypes Overlapping With Smooth Muscle Dysfunction Syndrome, Anita Kaw, Kaveeta Kaw, Ellen M Hostetler, Ana Beleza-Meireles, Adam Smith-Collins, Catherine Armstrong, Ingrid Scurr, Timothy Cotts, Rajani Aatre, Michael J Bamshad, Dawn Earl, Abraham Groner, Katherine Agre, Yehuda Raveh, Callie S Kwartler, Dianna M Milewicz

Faculty, Staff and Student Publications

Pathogenic variants in ACTA2, encoding smooth muscle α-actin, predispose to thoracic aortic aneurysms and dissections. ACTA2 variants altering arginine 179 predispose to a more severe, multisystemic disease termed smooth muscle dysfunction syndrome (SMDS; OMIM 613834). Vascular complications of SMDS include patent ductus arteriosus (PDA) or aortopulmonary window, early-onset thoracic aortic disease (TAD), moyamoya-like cerebrovascular disease, and primary pulmonary hypertension. Patients also have dysfunction of other smooth muscle-dependent systems, including congenital mydriasis, hypotonic bladder, and gut hypoperistalsis. Here, we describe five patients with novel heterozygous ACTA2 missense variants, p.Arg179Gly, p.Met46Arg, p.Thr204Ile, p.Arg39Cys, and p.Ile66Asn, who have clinical complications that align or …

An Integrated Proteomic And Glycoproteomic Investigation Reveals Alterations In The N-Glycoproteomic Network Induced By 2-Deoxy-D-Glucose In Colorectal Cancer Cells, Cheng Ma, Hong-Yuan Tsai, Qi Zhang, Lakmini Senavirathna, Lian Li, Lih-Shen Chin, Ru Chen, Sheng Pan

Faculty, Staff and Students Publications

As a well-known glycolysis inhibitor for anticancer treatment, 2-Deoxy-D-glucose (2DG) inhibits the growth and survival of cancer cells by interfering with the ATP produced by the metabolism of D-glucose. In addition, 2DG inhibits protein glycosylation in vivo by competing with D-mannose, leading to endoplasmic reticulum (ER) stress and unfolded protein responses in cancer cells. However, the molecular details underlying the impact of 2DG on protein glycosylation remain largely elusive. With an integrated approach to glycoproteomics and proteomics, we characterized the 2DG-induced alterations in N-glycosylation, as well as the cascading impacts on the whole proteome using the HT29 colorectal cancer …

Targeting De Novo Lipogenesis And The Lands Cycle Induces Ferroptosis In Kras-Mutant Lung Cancer, Caterina Bartolacci, Cristina Andreani, Gonçalo Vale, Stefano Berto, Margherita Melegari, Anna Colleen Crouch, Dodge L Baluya, George Kemble, Kurt Hodges, Jacqueline Starrett, Katerina Politi, Sandra L Starnes, Daniele Lorenzini, Maria Gabriela Raso, Luisa M Solis Soto, Carmen Behrens, Humam Kadara, Boning Gao, Ignacio I Wistuba, John D Minna, Jeffrey G Mcdonald, Pier Paolo Scaglioni

Faculty, Staff and Student Publications

Mutant KRAS (KM), the most common oncogene in lung cancer (LC), regulates fatty acid (FA) metabolism. However, the role of FA in LC tumorigenesis is still not sufficiently characterized. Here, we show that KMLC has a specific lipid profile, with high triacylglycerides and phosphatidylcholines (PC). We demonstrate that FASN, the rate-limiting enzyme in FA synthesis, while being dispensable in EGFR-mutant or wild-type KRAS LC, is required for the viability of KMLC cells. Integrating lipidomic, transcriptomic and functional analyses, we demonstrate that FASN provides saturated and monounsaturated FA to the Lands cycle, the process remodeling oxidized phospholipids, such as PC. Accordingly, …

Persistent Ethnicity-Associated Disparity In Anti-Tumor Effectiveness Of Immune Checkpoint Inhibitors Despite Equal Access, Marcus A Florez, Jan O Kemnade, Nan Chen, Wendy Du, Anita L Sabichi, Daniel Y Wang, Quillan Huang, Courtney N Miller-Chism, Aparna Jotwani, Albert C Chen, David Hernandez, Vlad C Sandulache

Faculty, Staff and Students Publications

We reviewed response to immune checkpoint inhibitors (ICI) of 207 patients with diagnoses of lung or head and neck cancer treated with chemotherapy/ICI combination therapy and ICI monotherapy between 2015 and 2020 at one of three clinical pavilions associated with the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine. Two of these pavilions (Harris Health System and the Michael E. DeBakey Veterans Affairs Medical Center) serve large minority populations and provide equal access to care regardless of means. 174 patients had a diagnosis of lung cancer (non-small cell or small cell) and 33 had a diagnosis of …

Characteristics Of Eating Behavior Profiles Among Preschoolers With Low-Income Backgrounds: A Person-Centered Analysis, Jennifer Orlet Fisher, Sheryl O Hughes, Alison L Miller, Mildred A Horodynski, Holly E Brophy-Herb, Dawn A Contreras, Niko Kaciroti, Karen E Peterson, Katherine L Rosenblum, Danielle Appugliese, Julie C Lumeng

Children’s Nutrition Research Center Staff Publications

Background: Individual differences in eating behaviors among young children are well-established, but the extent to which behaviors aggregate within individuals to form distinct eating behavior profiles remains unknown. Our objectives were to identify eating behavior profiles among preschool-aged children and evaluate associations with temperament and weight.

Methods: A secondary, cross-sectional analysis of baseline data from 2 cohort studies was conducted involving 1004 children aged 3-4 years and their parents with low-income backgrounds. Children's eating behaviors and temperament were assessed by parental report. Body mass index z-scores and weight status were calculated using measured heights and weights. Latent profile analysis (LPA) …

Tumor Microenvironment In Pancreatic Ductal Adenocarcinoma: Implications In Immunotherapy, Caitlyn Smith, Wei Zheng, Jixin Dong, Yaohong Wang, Jinping Lai, Xiuli Liu, Feng Yin

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma is one of the most aggressive and lethal cancers. Surgical resection is the only curable treatment option, but it is available for only a small fraction of patients at the time of diagnosis. With current therapeutic regimens, the average 5-year survival rate is less than 10% in pancreatic cancer patients. Immunotherapy has emerged as one of the most promising treatment options for multiple solid tumors of advanced stage. However, its clinical efficacy is suboptimal in most clinical trials on pancreatic cancer. Current studies have suggested that the tumor microenvironment is likely the underlying barrier affecting immunotherapy drug …

The Role Of Natural Products And Their Multitargeted Approach To Treat Solid Cancer, Naoshad Muhammad, Darksha Usmani, Mohammad Tarique, Huma Naz, Mohammad Ashraf, Ramesh Raliya, Shams Tabrez, Torki A Zughaibi, Ahdab Alsaieedi, Israa J Hakeem, Mohd Suhail

2020-Current year OA Pubs

Natural products play a critical role in the discovery and development of numerous drugs for the treatment of various types of cancer. These phytochemicals have demonstrated anti-carcinogenic properties by interfering with the initiation, development, and progression of cancer through altering various mechanisms such as cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis. Treating multifactorial diseases, such as cancer with agents targeting a single target, might lead to limited success and, in many cases, unsatisfactory outcomes. Various epidemiological studies have shown that the steady consumption of fruits and vegetables is intensely associated with a reduced risk of cancer. Since ancient period, plants, …

Association Of Cardiovascular Health Through Young Adulthood With Genome-Wide Dna Methylation Patterns In Midlife: The Cardia Study, Yinan Zheng, Brian T Joyce, Shih-Jen Hwang, Jiantao Ma, Lei Liu, Norrina B Allen, Amy E Krefman, Jun Wang, Tao Gao, Drew R Nannini, Haixiang Zhang, David R Jacobs, Myron D Gross, Myriam Fornage, Cora E Lewis, Pamela J Schreiner, Stephen Sidney, Dongquan Chen, Philip Greenland, Daniel Levy, Lifang Hou, Donald M Lloyd-Jones

Faculty, Staff and Student Publications

Background: Cardiovascular health (CVH) from young adulthood is strongly associated with an individual's future risk of cardiovascular disease (CVD) and total mortality. Defining epigenomic biomarkers of lifelong CVH exposure and understanding their roles in CVD development may help develop preventive and therapeutic strategies for CVD.

Methods: In 1085 CARDIA study (Coronary Artery Risk Development in Young Adults) participants, we defined a clinical cumulative CVH score that combines body mass index, blood pressure, total cholesterol, and fasting glucose measured longitudinally from young adulthood through middle age over 20 years (mean age, 25-45). Blood DNA methylation at >840 000 methylation markers was …

Validation Of Remote Height And Weight Assessment In A Rural Randomized Clinical Trial., Bethany Forseth Hanson, Ann M. Davis, Dana Bakula, Megan Murray, Kelsey Dean, Rebecca E. Swinburne Romine, Kandace Fleming

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The purpose of this study is to describe and assess a remote height and weight protocol that was developed for an ongoing trial conducted during the SARS COV-2 pandemic.

METHODS: Thirty-eight rural families (children 8.3 ± 0.7 years; 68% female; and caregivers 38.2 ± 6.1 years) were provided detailed instructions on how to measure height and weight. Families obtained measures via remote data collection (caregiver weight, child height and weight) and also by trained staff. Differences between data collection methods were examined.

RESULTS: Per absolute mean difference analyses, slightly larger differences were found for child weight (0.21 ± 0.21 …

Urinary Metabolites Of Polycyclic Aromatic Hydrocarbons In Firefighters: A Systematic Review And Meta-Analysis, Jooyeon Hwang, Chao Xu, Paul Grunsted, Robert J Agnew, Tara R Malone, Shari Clifton, Krista Thompson, Xin Xu

Faculty, Staff and Student Publications

Firefighters are intermittently exposed to complex, mixed pollutants in random settings. Of those pollutants, PAHs (polycyclic aromatic hydrocarbons) are the most commonly studied and best understood. PAH exposure can occur via multiple routes; therefore, the levels of hydroxylated metabolites of PAHs in urine have been used as a biomonitoring tool for risk assessment. We performed a systematic review and meta-analysis of the literature to estimate the levels of urinary hydroxylated PAH (OHPAH) among firefighters, determine risk attributions, and, finally, evaluate the scope of preventive efforts and their utility as diagnostic tools. The meta-regression confirmed increases in OHPAH concentrations after fire …

Microbial Liberation Of N-Methylserotonin From Orange Fiber In Gnotobiotic Mice And Humans, Nathan D Han, Daniel Webber, Stacey Marion, Michael J Barratt, Andrew C Heath, Et Al.

2020-Current year OA Pubs

Plant fibers in byproduct streams produced by non-harsh food processing methods represent biorepositories of diverse, naturally occurring, and physiologically active biomolecules. To demonstrate one approach for their characterization, mass spectrometry of intestinal contents from gnotobiotic mice, plus in vitro studies, revealed liberation of N-methylserotonin from orange fibers by human gut microbiota members including Bacteroides ovatus. Functional genomic analyses of B. ovatus strains grown under permissive and non-permissive N-methylserotonin "mining" conditions revealed polysaccharide utilization loci that target pectins whose expression correlate with strain-specific liberation of this compound. N-methylserotonin, orally administered to germ-free mice, reduced adiposity, altered liver glycogenesis, shortened gut transit …

Birth Length Is The Strongest Predictor Of Linear Growth Status And Stunting In The First 2 Years Of Life After A Preconception Maternal Nutrition Intervention: The Children Of The Women First Trial, Nancy F Krebs, K Michael Hambidge, Jamie L Westcott, Ana L Garcés, Lester Figueroa, Antoinette K Tshefu, Adrien L Lokangaka, Shivaprasad S Goudar, Sangappa M Dhaded, Sarah Saleem, Sumera Aziz Ali, Melissa S Bauserman, Richard J Derman, Robert L Goldenberg, Abhik Das, Dhuly Chowdhury

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: The multicountry Women First trial demonstrated that nutritional supplementation initiated prior to conception (arm 1) or early pregnancy (arm 2) and continued until delivery resulted in significantly greater length at birth and 6 mo compared with infants in the control arm (arm 3).

OBJECTIVES: We evaluated intervention effects on infants' longitudinal growth trajectory from birth through 24 mo and identified predictors of length status and stunting at 24 mo.

METHODS: Infants' anthropometry was obtained at 6, 12, 18, and 24 mo after the Women First trial (registered at clinicaltrials.gov as NCT01883193), which was conducted in low-resource settings: Democratic Republic …

Epixplorer: A Web Server For Prediction, Analysis And Visualization Of Enhancer-Promoter Interactions, Li Tang, Zhizhou Zhong, Yisheng Lin, Yifei Yang, Jun Wang, James F Martin, Min Li

Children’s Nutrition Research Center Staff Publications

Long distance enhancers can physically interact with promoters to regulate gene expression through formation of enhancer-promoter (E-P) interactions. Identification of E-P interactions is also important for profound understanding of normal developmental and disease-associated risk variants. Although the state-of-art predictive computation methods facilitate the identification of E-P interactions to a certain extent, currently there is no efficient method that can meet various requirements of usage. Here we developed EPIXplorer, a user-friendly web server for efficient prediction, analysis and visualization of E-P interactions. EPIXplorer integrates 9 robust predictive algorithms, supports multiple types of 3D contact data and multi-omics data as input. The …

Antibody Responses To Sars-Cov-2 After Infection Or Vaccination In Children And Young Adults With Inflammatory Bowel Disease., Joelynn Dailey, Lina Kozhaya, Mikail Dogan, Dena Hopkins, Blaine Lapin, Katherine Herbst, Michael Brimacombe, Kristen Grandonico, Fatih Karabacak, John Schreiber, Bruce Tsan-Liang Liang, Juan C Salazar, Derya Unutmaz, Jeffrey S Hyams

Faculty Research 2022

BACKGROUND: Characterization of neutralization antibodies to SARS-CoV-2 infection or vaccination in children and young adults with inflammatory bowel disease (IBD) receiving biologic therapies is crucial.

METHODS: We performed a prospective longitudinal cohort study evaluating SARS-CoV-2 spike protein receptor binding domain (S-RBD) IgG positivity along with consistent clinical symptoms in patients with IBD receiving infliximab or vedolizumab. Serum was also obtained following immunization with approved vaccines. The IgG antibody to the spike protein binding domain of SARS-CoV-2 was assayed with a fluorescent bead-based immunoassay that takes advantage of the high dynamic range of fluorescent molecules using flow cytometry. A sensitive and …

Drive Leg Ground Reaction Forces And Rate Of Force Development Over Consecutive Windmill Softball Pitches, Erin R. Pletcher, Kenzie B. Friesen, Gretchen D. Oliver, Mita Lovalekar, Keith Gorse, Takashi Nagai, Chris Connaboy

Department of Exercise Science Faculty Papers

BACKGROUND: Windmill softball pitching is a highly skilled movement, combining whole body coordination with explosive force. Successful pitching requires sequential movement to transfer energy produced by the lower extremity to the pitching arm. Therefore, drive leg ground reaction force (GRF) and the time over which a pitcher can develop force during push off, defined as rate of force development (RFD), is essential for optimal performance. The aim of this study was to examine GRF and RFD in the drive leg during the windmill softball pitch, as well as pitch velocity, throughout a simulated game.

METHODS: Fourteen softball pitchers (17.9±2.3 years, …

Disease Burden And Management Of Crigler-Najjar Syndrome: Report Of A World Registry, Sem J Aronson, Norman Junge, Mediha Trabelsi, Wided Kelmemi, Aurelie Hubert, Karlla W Brigatti, Michael D. Fox, Robert J De Knegt, Johanna C Escher, Virginia M Ginocchio, Raffaele Iorio, Yan Zhu, Figen Özçay, Fakher Rahim, Mortada H F El-Shabrawi, Eyal Shteyer, Angelo Di Giorgio, Lorenzo D'Antiga, Federico Mingozzi, Nicola Brunetti-Pierri, Kevin A Strauss, Philippe Labrune, Ridha Mrad, Ulrich Baumann, Ulrich Beuers, Piter J Bosma

Department of Pediatrics Faculty Papers

Background and Aims Crigler-Najjar syndrome (CNS) is a disorder of bilirubin conjugation leading to brain damage and death without treatment. Although cohort studies of limited size have been published, uncertainty about outcome, co-morbidities, occurence of liver fibrosis and treatment outcome remains. With this worldwide cohort study, we aim to add substantial knowledge to the previously published data.

Methods Anonymized retrospective data of CNS patients were collected in a web-based registry platform.

Results Clinical data of 221 CNS patients (46% female, severe phenotype n = 209) were collected. At the time of analysis, 59 CNS patients were deceased. Mean serum total …

United States Healthcare Burden Of Pediatric Functional Gastrointestinal Pain Disorder Hospitalizations From 2002 To 2018, John M Hollier, Jason L Salemi, Robert J Shulman

Faculty, Staff and Students Publications

BACKGROUND: The healthcare burden of pediatric functional gastrointestinal pain disorders (FGIDs) is unclear. Our study aimed to characterize the burden of these hospitalizations in the United States (US).

METHODS: We utilized the US National Inpatient Sample from 2002 to 2018 to capture pediatric hospitalizations (ages 4 to 18 years old) with a primary discharge diagnosis of abdominal pain, constipation, irritable bowel syndrome, dyspepsia, abdominal migraine, cyclic vomiting syndrome, or fecal incontinence. We calculated the FGID hospitalization prevalence rate, length of stay (LOS), and inflation-adjusted costs annually and assessed for statistically significant trend changes using joinpoint analyses.

KEY RESULTS: 22.3 million …

Comparative Effectiveness Of Diversion Of Cerebrospinal Fluid For Children With Severe Traumatic Brain Injury, Michael J Bell, Jose Pineda, Et Al.

2020-Current year OA Pubs

Importance: Diversion of cerebrospinal fluid (CSF) has been used for decades as a treatment for children with severe traumatic brain injury (TBI) and is recommended by evidenced-based guidelines. However, these recommendations are based on limited studies.

Objective: To determine whether CSF diversion is associated with improved Glasgow Outcome Score-Extended for Pediatrics (GOS-EP) and decreased intracranial pressure (ICP) in children with severe TBI.

Design, Setting, and Participants: This observational comparative effectiveness study was performed at 51 clinical centers that routinely care for children with severe TBI in 8 countries (US, United Kingdom, Spain, the Netherlands, Australia, New Zealand, South Africa, and …

Maternal Obesity, Pregnancy Weight Gain, And Birth Weight And Risk Of Colorectal Cancer, Caitlin C Murphy, Piera M Cirillo, Nickilou Y Krigbaum, Amit G Singal, Minjae Lee, Timothy Zaki, Ezra Burstein, Barbara A Cohn

Faculty, Staff and Student Publications

Objective: Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. Obesity is a well-established risk factor for CRC, and fetal or developmental origins of obesity may underlie its effect on cancer in adulthood. We examined associations of maternal obesity, pregnancy weight gain, and birth weight and CRC in adult offspring.

Design: The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California (N=18 751 live births among 14 507 mothers). Clinical information was abstracted from mothers' medical records 6 months prior to pregnancy through delivery. Diagnoses of …

The 5th Edition Of The World Health Organization Classification Of Haematolymphoid Tumours: Lymphoid Neoplasms, Rita Alaggio, Catalina Amador, Ioannis Anagnostopoulos, Ayoma D Attygalle, Iguaracyra Barreto De Oliveira Araujo, Emilio Berti, Govind Bhagat, Anita Maria Borges, Daniel Boyer, Mariarita Calaminici, Amy Chadburn, John K C Chan, Wah Cheuk, Wee-Joo Chng, John K Choi, Shih-Sung Chuang, Sarah E Coupland, Magdalena Czader, Sandeep S Dave, Daphne De Jong, Ming-Qing Du, Kojo S Elenitoba-Johnson, Judith Ferry, Julia Geyer, Dita Gratzinger, Joan Guitart, Sumeet Gujral, Marian Harris, Christine J Harrison, Sylvia Hartmann, Andreas Hochhaus, Patty M Jansen, Kennosuke Karube, Werner Kempf, Joseph Khoury, Hiroshi Kimura, Wolfram Klapper, Alexandra E Kovach, Shaji Kumar, Alexander J Lazar, Stefano Lazzi, Lorenzo Leoncini, Nelson Leung, Vasiliki Leventaki, Xiao-Qiu Li, Megan S Lim, Wei-Ping Liu, Abner Louissaint, Andrea Marcogliese, L Jeffrey Medeiros, Michael Michal, Roberto N Miranda, Christina Mitteldorf, Santiago Montes-Moreno, William Morice, Valentina Nardi, Kikkeri N Naresh, Yasodha Natkunam, Siok-Bian Ng, Ilske Oschlies, German Ott, Marie Parrens, Melissa Pulitzer, S Vincent Rajkumar, Andrew C Rawstron, Karen Rech, Andreas Rosenwald, Jonathan Said, Clémentine Sarkozy, Shahin Sayed, Caner Saygin, Anna Schuh, William Sewell, Reiner Siebert, Aliyah R Sohani, Reuben Tooze, Alexandra Traverse-Glehen, Francisco Vega, Beatrice Vergier, Ashutosh D Wechalekar, Brent Wood, Luc Xerri, Wenbin Xiao

Faculty, Staff and Student Publications

We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as …

Insurance Coverage And Respiratory Morbidities In Bronchopulmonary Dysplasia., Joseph M. Collaco, Michael C. Tracy, Catherine A. Sheils, Jessica L. Rice, Lawrence M. Rhein, Leif D. Nelin, Paul E. Moore, Winston M. Manimtim, Jonathan C. Levin, Khanh Lai, Lystra P. Hayden, Julie L. Fierro, Eric D. Austin, Stamatia Alexiou, Amit Agarwal, Natalie Villafranco, Roopa Siddaiah, Antonia P. Popova, Ioana A. Cristea, Christopher D. Baker, Manvi Bansal, Sharon A. Mcgrath-Morrow

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Preterm infants and young children with bronchopulmonary dysplasia (BPD) are at increased risk for acute care utilization and chronic respiratory symptoms during early life. Identifying risk factors for respiratory morbidities in the outpatient setting could decrease the burden of care. We hypothesized that public insurance coverage was associated with higher acute care usage and respiratory symptoms in preterm infants and children with BPD after initial neonatal intensive care unit (NICU) discharge.

METHODS: Subjects were recruited from BPD clinics at 10 tertiary care centers in the United States between 2018 and 2021. Demographics and clinical characteristics were obtained through chart …

A Novel, De Novo Intronic Variant In Pogz Causes White-Sutton Syndrome, Ashanta Merriweather, David R Murdock, Jill A Rosenfeld, Hongzheng Dai, Shamika Ketkar, Lisa Emrick, Sarah Nicholas, Richard A Lewis, Undiagnosed Diseases Network, Carlos A Bacino, Daryl A Scott, Brendan Lee, Vernon Reid Sutton, Lorraine Potocki, Lindsay C Burrage

Center for Medical Ethics and Health Policy Staff Publications

White-Sutton syndrome (WHSUS), which is caused by heterozygous pathogenic variants in POGZ, is characterized by a spectrum of intellectual disabilities and global developmental delay with or without features of autism spectrum disorder. Additional features may include hypotonia, behavioral abnormalities, ophthalmic abnormalities, hearing loss, sleep apnea, microcephaly, dysmorphic facial features, and rarely, congenital diaphragmatic hernia (CDH). We present a 6-year-old female with features of WHSUS, including CDH, but with nondiagnostic clinical trio exome sequencing. Exome sequencing reanalysis revealed a heterozygous, de novo, intronic variant in POGZ (NM_015100.3:c.2546-20T>A). RNA sequencing revealed that this intronic variant leads to skipping of exon 18. …