Digital Commons Network^™

A Pragmatic Machine Learning Model To Predict Carbapenem Resistance, Ryan J Mcguire, Sean C Yu, Philip R O Payne, Albert M Lai, M Cristina Vazquez-Guillamet, Marin H Kollef, Andrew P Michelson

Open Access Publications

Infection caused by carbapenem-resistant (CR) organisms is a rising problem in the United States. While the risk factors for antibiotic resistance are well known, there remains a large need for the early identification of antibiotic-resistant infections. Using machine learning (ML), we sought to develop a prediction model for carbapenem resistance. All patients >18 years of age admitted to a tertiary-care academic medical center between 1 January 2012 and 10 October 2017 with ≥1 bacterial culture were eligible for inclusion. All demographic, medication, vital sign, procedure, laboratory, and culture/sensitivity data were extracted from the electronic health record. Organisms were considered CR …

Prognostic Factors For Chronic Post-Surgical Pain After Lung Or Pleural Surgery: A Protocol For A Systematic Review And Meta-Analysis, Pascal Richard David Clephas, Sanne Elisabeth Hoeks, Marialena Trivella, Christian S Guay, Preet Mohinder Singh, Markus Klimek, Michael Heesen

Open Access Publications

INTRODUCTION: Chronic post-surgical pain (CPSP) after lung or pleural surgery is a common complication and associated with a decrease in quality of life, long-term use of pain medication and substantial economic costs. An abundant number of primary prognostic factor studies are published each year, but findings are often inconsistent, methods heterogeneous and the methodological quality questionable. Systematic reviews and meta-analyses are therefore needed to summarise the evidence.

METHODS AND ANALYSIS: The reporting of this protocol adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) checklist. We will include retrospective and prospective studies with a follow-up of …

Outcomes Of Rescue Endovascular Treatment Of Emergent Large Vessel Occlusion In Patients With Underlying Intracranial Atherosclerosis: Insights From Star, Sami Al Kasab, Joshua Osbun, Et Al

Open Access Publications

Background Some emergent large vessel occlusions (ELVOs) are refractory to reperfusion because of underlying intracranial atherosclerosis (ICAS), often requiring rescue therapy (RT) with balloon angioplasty, stenting, or both. In this study, we investigate the safety, efficacy, and long-term outcomes of RT in the setting of mechanical thrombectomy for ICAS-related ELVO. Methods and Results We queried the databases of 10 thrombectomy-capable centers in North America and Europe included in STAR (Stroke Thrombectomy and Aneurysm Registry). Patients with ELVO who underwent ICAS-related RT were included. A matched sample was produced for variables of age, admission National Institute of Health Stroke Scale, Alberta …

A Phase 2a Randomized Clinical Trial Of Intravenous Vedolizumab For The Treatment Of Steroid-Refractory Intestinal Acute Graft-Versus-Host Disease, Yngvar Fløisand, Mark A Schroeder, Patrice Chevallier, Dominik Selleslag, Steven Devine, Anne S Renteria, Mohamad Mohty, Ibrahim Yakoub-Agha, Chunlin Chen, Andrejus Parfionovas, Syed Quadri, Johan Jansson, Mona Akbari, Yi-Bin Chen

Open Access Publications

Steroid-refractory (SR) acute graft-versus-host disease (aGvHD) remains a significant complication after allogeneic hematopoietic cell transplantation. Systemic corticosteroids are first-line therapy for aGvHD, but apart from ruxolitinib, there are no approved treatments for SR aGvHD. Vedolizumab is approved for treatment of ulcerative colitis and Crohn's disease, and may be effective for treatment of SR intestinal aGvHD. We conducted a phase 2a trial (NCT02993783) to evaluate the clinical efficacy, tolerability, and safety of vedolizumab 300 and 600 mg for SR intestinal aGvHD. This study was terminated before full enrollment was completed because early results failed to demonstrate positive proof-of-concept in efficacy. Before …

Balancing Serendipity And Reproducibility: Pluripotent Stem Cells As Experimental Systems For Intellectual And Developmental Disorders, Nickesha C Anderson, Pin-Fang Chen, Kesavan Meganathan, Wardiya Afshar Saber, Andrew J Petersen, Anita Bhattacharyya, Kristen L Kroll, Mustafa Sahin, Cross-Iddrc Human Stem Cell Working Group

Open Access Publications

Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) and their differentiation into neural lineages is a revolutionary experimental system for studying neurological disorders, including intellectual and developmental disabilities (IDDs). However, issues related to variability and reproducibility have hindered translating preclinical findings into drug discovery. Here, we identify areas for improvement by conducting a comprehensive review of 58 research articles that utilized iPSC-derived neural cells to investigate genetically defined IDDs. Based upon these findings, we propose recommendations for best practices that can be adopted by research scientists as well as journal editors.

Placental Pathology In An Unsuspected Case Of Mucolipidosis Type Ii With Secondary Hyperparathyroidism In A Premature Infant, Parith Wongkittichote, Garland Michael Upchurch, Louis P Dehner, Timothy Wood, Jorge L Granadillo

Open Access Publications

Mucolipidosis type II (MLII, MIM 252500) is a lysosomal storage disorders caused by defects in

N-Cadherin In Osteolineage Cells Modulates Stromal Support Of Tumor Growth, Francesca Fontana, Jingyu Xiang, Xinming Su, Eric Tycksen, Rachel Nassau, Gregory Fox, Giulia Leanza, Katherine Weilbaecher, Roberto Civitelli

Open Access Publications

Tumor growth and metastases are dependent on interactions between cancer cells and the local environment. Expression of the cell-cell adhesion molecule N-cadherin (Ncad) is associated with highly aggressive cancers, and its expression by osteogenic cells has been proposed to provide a molecular "dock" for disseminated tumor cells to establish in pre-metastatic niches within the bone. To test this biologic model, we conditionally deleted the Ncad gene (

Clinical Implications Of Estimated Glomerular Filtration Rate Dip Following Sodium-Glucose Cotransporter-2 Inhibitor Initiation On Cardiovascular And Kidney Outcomes, Yan Xie, Benjamin Bowe, Andrew K Gibson, Janet B Mcgill, Geetha Maddukuri, Ziyad Al-Aly

Open Access Publications

Background The frequency of the initial short-term decline in estimated glomerular filtration rate (eGFR), eGFR dip, following initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and its clinical implications in real-world practice are not clear. Methods and Results We built a cohort of 36 638 new users of SGLT2i and 209 025 new users of other antihyperglycemics. Inverse probability weighting was used to estimate the excess rate of eGFR dip, risk of the composite cardiovascular outcome of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, or all-cause mortality, and risk of the composite kidney outcome of eGFR decline >50%, end-stage kidney …

Cardiovascular Adverse Events Associated With Braf Versus Braf/Mek Inhibitor: Cross-Sectional And Longitudinal Analysis Using Two Large National Registries, Avirup Guha, Prantesh Jain, Michael G Fradley, Daniel Lenihan, Jahir M Gutierrez, Chhavi Jain, Marcos De Lima, Jill S Barnholtz-Sloan, Guilherme H Oliveira, Afshin Dowlati, Sadeer Al-Kindi

Open Access Publications

BACKGROUND: Cardiovascular adverse events (CVAEs) associated with BRAF inhibitors alone versus combination BRAF/MEK inhibitors are not fully understood.

METHODS: This study included all adult patients who received BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) or combinations BRAF/MEK inhibitors (vemurafenib/cobimetinib; dabrafenib/trametinib; encorafenib/binimetinib). We utilized the cross-sectional FDA's Adverse Events Reporting System (FAERS) and longitudinal Truven Health Analytics/IBM MarketScan database from 2011 to 2018. Various CVAEs, including arterial hypertension, heart failure (HF), and venous thromboembolism (VTE), were studied using adjusted regression techniques.

RESULTS: In FAERS, 7752 AEs were reported (40% BRAF and 60% BRAF/MEK). Median age was 60 (IQR 49-69) years with 45% females …

Cardiac Safety Of Trabectedin Monotherapy Or In Combination With Pegylated Liposomal Doxorubicin In Patients With Sarcomas And Ovarian Cancer, Robin L Jones, Thomas J Herzog, Shreyaskumar R Patel, Margaret Von Mehren, Scott M Schuetze, Brian A Van Tine, Robert L Coleman, Roland Knoblauch, Spyros Triantos, Peter Hu, Waleed Shalaby, Tracy Mcgowan, Bradley J Monk, George D Demetri

Open Access Publications

BACKGROUND: As with other alkylating agents, cardiac dysfunction can occur with trabectedin therapy for advanced soft tissue sarcomas (STS) or recurrent ovarian cancer (ROC) where treatment options for advanced disease are still limited. Cardiac safety for trabectedin monotherapy (T) for STS or in combination with pegylated liposomal doxorubicin (T+PLD) for ROC was evaluated in this retrospective postmarketing regulatory commitment.

METHODS: Patient data for multiple cardiac-related treatment-emergent adverse events (cTEAEs) were evaluated in pooled analyses of ten phase 2 trials, one phase 3 trial in STS (n = 982), and two phase 3 trials in ROC (n = 1231).

RESULTS: Multivariate …

Epidemic Preparedness: Prenatal Zika Virus Screening During The Next Epidemic, Luxi Qiao, Celina M Turchi Martelli, Amber I Raja, Nuria Sanchez Clemente, Thalia Velho Barreto De Araùjo, Ricardo Arraes De Alencar Ximenes, Demócrito De Barros Miranda-Filho, Anna Ramond, Elizabeth B Brickley

Open Access Publications

Zika virus (ZIKV) is a vectorborne infectious agent of global public health significance due to its potential to cause severe teratogenic outcomes. The question of whether health systems should consider adopting screening programmes for ZIKV infections during pregnancy warrants consideration. In this analysis, we apply the Wilson-Jungner framework to appraise the potential utility of a prenatal ZIKV screening programme, outline potential screening strategies within the case-finding pathway, and consider other epidemiological factors that may influence the planning of such a screening programme. Our evaluation of a potential prenatal ZIKV screening programme highlights factors affirming its usefulness, including the importance of …

Longitudinal Data Reveal Strong Genetic And Weak Non-Genetic Components Of Ethnicity-Dependent Blood Dna Methylation Levels, Chris Mckennan, Katherine Naughton, Catherine Stanhope, Meyer Kattan, George T O'Connor, Megan T Sandel, Cynthia M Visness, Robert A Wood, Leonard B Bacharier, Avraham Beigelman, Stephanie Lovinsky-Desir, Alkis Togias, James E Gern, Dan Nicolae, Carole Ober

Open Access Publications

Epigenetic architecture is influenced by genetic and environmental factors, but little is known about their relative contributions or longitudinal dynamics. Here, we studied DNA methylation (DNAm) at over 750,000 CpG sites in mononuclear blood cells collected at birth and age 7 from 196 children of primarily self-reported Black and Hispanic ethnicities to study race-associated DNAm patterns. We developed a novel Bayesian method for high-dimensional longitudinal data and showed that race-associated DNAm patterns at birth and age 7 are nearly identical. Additionally, we estimated that up to 51% of all self-reported race-associated CpGs had race-dependent DNAm levels that were mediated through …

Restless Legs Syndrome Shows Increased Silent Postmortem Cerebral Microvascular Disease With Gliosis, Arthur S Walters, Paisit Paueksakon, Charles H Adler, Michael Moussouttas, Leonard B Weinstock, Karen Spruyt, Kanika Bagai

Open Access Publications

Background Patients with restless legs syndrome (RLS) have increased silent microvascular disease by magnetic resonance imaging. However, there has been no previous autopsy confirmation of these magnetic resonance imaging findings. RLS is also frequently associated with inflammatory and immunologically mediated medical disorders. The postmortem cortex in patients with RLS was therefore evaluated for evidence of microvascular and immunological changes. Methods and Results Ten microvascular injury samples of precentral gyrus in 5 patients with RLS (3 men, 2 women; mean age, 81 years) and 9 controls (2 men, 7 women; mean age, 90 years) were studied by hematoxylin and eosin stains …

Examination Of A Blood-Brain Barrier Targeting Β-Galactosidase-Monoclonal Antibody Fusion Protein In A Murine Model Of Gm1-Gangliosidosis, Michael J Przybilla, Christine Stewart, Timothy W Carlson, Li Ou, Brenda L Koniar, Rohini Sidhu, Pamela J Kell, Xuntian Jiang, Jeanine R Jarnes, M Gerard O'Sullivan, Chester B Whitley

Open Access Publications

GM1-gangliosidosis is a lysosomal disease resulting from a deficiency in the hydrolase β-galactosidase (β-gal) and subsequent accumulation of gangliosides, primarily in neuronal tissue, leading to progressive neurological deterioration and eventually early death. Lysosomal diseases with neurological involvement have limited non-invasive therapies due to the inability of lysosomal enzymes to cross the blood-brain barrier (BBB). A novel fusion enzyme, labeled mTfR-GLB1, was designed to act as a ferry across the BBB by fusing β-gal to the mouse monoclonal antibody against the mouse transferrin receptor and tested in a murine model of GM1-gangliosidosis (β-gal

A Cardiac Rehabilitation Program For Breast Cancer Survivors: A Feasibility Study, Filadelfiya Zvinovski, Julie A Stephens, Bhuvaneswari Ramaswamy, Raquel E Reinbolt, Anne M Noonan, Jeffrey Bryan Vandeusen, Robert Wesolowski, Daniel G Stover, Nicole Olivia Williams, Sagar D Sardesai, Laxmi Mehta, Randi Foraker, Martha Gulati, Maryam Lustberg, Allison M Quick

Open Access Publications

Purpose: The purpose of this study was to determine the feasibility and preliminary efficacy of a cardiac rehabilitation (CR) intervention in the breast cancer population.

Methods: This single-arm feasibility study evaluated a 14-week CR intervention program in breast cancer survivors. Feasibility was defined as completion of at least 30/36 sessions of the program without serious adverse events (SAE) in 80% of patients. Secondary endpoints included the change in VO2 max, cardiovascular disease (CVD) risk factors, Duke Activity Secondary Index (DASI), Brief Fatigue Inventory (BFI), and QLQ-C30. All outcomes were reported as mean change and compared using paired

Results: A total …

Spontaneous Neural Synchrony Links Intrinsic Spinal Sensory And Motor Networks During Unconsciousness, Jacob Graves Mcpherson, Maria F. Bandres

Open Access Publications

Non-random functional connectivity during unconsciousness is a defining feature of supraspinal networks. However, its generalizability to intrinsic spinal networks remains incompletely understood. Previously, Barry et al., 2014 used fMRI to reveal bilateral resting state functional connectivity within sensory-dominant and, separately, motor-dominant regions of the spinal cord. Here, we record spike trains from large populations of spinal interneurons in vivo in rats and demonstrate that spontaneous functional connectivity also links sensory- and motor-dominant regions during unconsciousness. The spatiotemporal patterns of connectivity could not be explained by latent afferent activity or by populations of interconnected neurons spiking randomly. We also document connection …

Cellular, Circuit And Transcriptional Framework For Modulation Of Itch In The Central Amygdala, Vijay K. Samineni, Jose G. Grajales-Reyes, Gary E. Grajales-Reyes, Eric Tycksen, Bryan A. Copits, Christian Pedersen, Edem S. Ankudey, Julian N. Sackey, Sienna B. Sewell, Michael R. Bruchas, Robert W. Gereau

Open Access Publications

Itch is an unpleasant sensation that elicits robust scratching and aversive experience. However, the identity of the cells and neural circuits that organize this information remains elusive. Here, we show the necessity and sufficiency of chloroquine-activated neurons in the central amygdala (CeA) for both itch sensation and associated aversion. Further, we show that chloroquine-activated CeA neurons play important roles in itch-related comorbidities, including anxiety-like behaviors, but not in some aversive and appetitive behaviors previously ascribed to CeA neurons. RNA-sequencing of chloroquine-activated CeA neurons identified several differentially expressed genes as well as potential key signaling pathways in regulating pruritis. Finally, viral …

Phenotypic And Genomic Profiling Of Staphylococcus Argenteus In Canada And The United States And Recommendations For Clinical Result Reporting, Alireza Eshaghi, Carl Bommersbach, Sandra Zittermann, C A Burnham, Robin Patel, Audrey N Schuetz, Samir N Patel, Julianne V Kus

Open Access Publications

No abstract provided.

Value Cmr: Towards A Comprehensive, Rapid, Cost-Effective Cardiovascular Magnetic Resonance Imaging, El-Sayed H Ibrahim, Luba Frank, Dhiraj Baruah, V Emre Arpinar, Andrew S Nencka, Kevin M Koch, L Tugan Muftuler, Orhan Unal, Jadranka Stojanovska, Jason C Rubenstein, Sherry-Ann Brown, John Charlson, Elizabeth M Gore, Carmen Bergom

Open Access Publications

Cardiac magnetic resonance imaging (CMR) is considered the gold standard for measuring cardiac function. Further, in a single CMR exam, information about cardiac structure, tissue composition, and blood flow could be obtained. Nevertheless, CMR is underutilized due to long scanning times, the need for multiple breath-holds, use of a contrast agent, and relatively high cost. In this work, we propose a rapid, comprehensive, contrast-free CMR exam that does not require repeated breath-holds, based on recent developments in imaging sequences. Time-consuming conventional sequences have been replaced by advanced sequences in the proposed CMR exam. Specifically, conventional 2D cine and phase-contrast (PC) …

Bundle-Specific Associations Between White Matter Microstructure And Aβ And Tau Pathology In Preclinical Alzheimer's Disease, Alexa Pichet Binette, Tammie Benzinger, John Morris, Randall Bateman, Et Al

Open Access Publications

Beta-amyloid (Aβ) and tau proteins, the pathological hallmarks of Alzheimer's disease (AD), are believed to spread through connected regions of the brain. Combining diffusion imaging and positron emission tomography, we investigated associations between white matter microstructure specifically in bundles connecting regions where Aβ or tau accumulates and pathology. We focused on free-water-corrected diffusion measures in the anterior cingulum, posterior cingulum, and uncinate fasciculus in cognitively normal older adults at risk of sporadic AD and presymptomatic mutation carriers of autosomal dominant AD. In Aβ-positive or tau-positive groups, lower tissue fractional anisotropy and higher mean diffusivity related to greater Aβ and tau …

Recovery Of Consciousness And Cognition After General Anesthesia In Humans, George A. Mashour, Ben J.A. Palanca, Wei Wang, Nan Lin, Maxwell Muench, Hannah Maybrier, Michael S. Avidan, Et Al

Open Access Publications

Understanding how the brain recovers from unconsciousness can inform neurobiological theories of consciousness and guide clinical investigation. To address this question, we conducted a multicenter study of 60 healthy humans, half of whom received general anesthesia for 3 hr and half of whom served as awake controls. We administered a battery of neurocognitive tests and recorded electroencephalography to assess cortical dynamics. We hypothesized that recovery of consciousness and cognition is an extended process, with differential recovery of cognitive functions that would commence with return of responsiveness and end with return of executive function, mediated by prefrontal cortex. We found that, …

Genetic Causes Of Cardiomyopathy In Children: First Results From The Pediatric Cardiomyopathy Genes Study, Stephanie M Ware, Charles E Canter, Et Al

Open Access Publications

Background Pediatric cardiomyopathy is a genetically heterogeneous disease with substantial morbidity and mortality. Current guidelines recommend genetic testing in children with hypertrophic, dilated, or restrictive cardiomyopathy, but practice variations exist. Robust data on clinical testing practices and diagnostic yield in children are lacking. This study aimed to identify the genetic causes of cardiomyopathy in children and to investigate clinical genetic testing practices. Methods and Results Children with familial or idiopathic cardiomyopathy were enrolled from 14 institutions in North America. Probands underwent exome sequencing. Rare sequence variants in 37 known cardiomyopathy genes were assessed for pathogenicity using consensus clinical interpretation guidelines. …

Obese Endometrial Cancer Survivors' Perceptions Of Weight Loss Strategies And Characteristics That May Influence Participation In Behavioral Interventions, Elise M Wilson, Abigail S Zamorano, Jingxia Liu, David Morris, Andrea Leon, Lindsay M Kuroki, Premal H Thaker, Carolyn K Mccourt, Katherine C Fuh, Matthew A Powell, David G Mutch, Graham A Colditz, Andrea R Hagemann

Open Access Publications

We aimed to evaluate obese endometrial cancer (EC) survivors' perceptions of weight loss barriers and previously attempted weight loss methods and to identify characteristics that predicted willingness to enroll in a behavioral intervention trial. We administered a 27-question baseline survey at an academic institution to EC survivors with body mass index ≥ 30 kg/m

Effects Of Community-Based Antiretroviral Therapy Initiation Models On Hiv Treatment Outcomes: A Systematic Review And Meta-Analysis, Ingrid Eshun-Wilson, Ajibola A. Awotiwon, Ashley Germann, Sophia A. Amankwaa, Nathan Ford, Sheree Schwartz, Stefan Baral, Elvin H. Geng

Open Access Publications

BACKGROUND: Antiretroviral therapy (ART) initiation in the community and outside of a traditional health facility has the potential to improve linkage to ART, decongest health facilities, and minimize structural barriers to attending HIV services among people living with HIV (PLWH). We conducted a systematic review and meta-analysis to determine the effect of offering ART initiation in the community on HIV treatment outcomes.

METHODS AND FINDINGS: We searched databases between 1 January 2013 and 22 February 2021 to identify randomized controlled trials (RCTs) and observational studies that compared offering ART initiation in a community setting to offering ART initiation in a …

Epigenomic Regulation Of Human T-Cell Leukemia Virus By Chromatin-Insulator Ctcf, Xiaogang Cheng, Ancy Joseph, Victor Castro, Alice Chen-Liaw, Zachary Skidmore, Takaharu Ueno, Jun-Ichi Fujisawa, Daniel A. Rauch, Grant A. Challen, Michael P. Martinez, Patrick Green, Malachi Griffith, Jacqueline E. Payton, John R. Edwards, Lee Ratner

Open Access Publications

Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes an aggressive T-cell malignancy and a variety of inflammatory conditions. The integrated provirus includes a single binding site for the epigenomic insulator, CCCTC-binding protein (CTCF), but its function remains unclear. In the current study, a mutant virus was examined that eliminates the CTCF-binding site. The mutation did not disrupt the kinetics and levels of virus gene expression, or establishment of or reactivation from latency. However, the mutation disrupted the epigenetic barrier function, resulting in enhanced DNA CpG methylation downstream of the CTCF binding site on both strands of …

Postsurgical Presentation Of Zollinger-Ellison Syndrome After Resection Of Endometrioid Neuroendocrine Tumor, Aymen Almuhaidb, Nicholas O Davidson

Open Access Publications

Zollinger-Ellison syndrome is a functional neuroendocrine tumor with inappropriate gastrin secretion and hyperchlorhydria causing severe peptic ulcer disease and chronic diarrhea. Although 70% of primary gastrinomas occur in the region of the duodenum, the diagnosis and localization of gastrinomas can be challenging because of small lesions that may arise functionally as lymph node metastases at initial presentation. We report a 76-year-old woman presenting with Zollinger-Ellison syndrome several months after surgical resection of endometrioid small cell neuroendocrine carcinoma and endometrioid adenocarcinoma.

A Phase 2, Double-Blind, Randomized, Dose-Ranging Trial Of Reldesemtiv In Patients With Als, Jeremy M. Shefner, Timothy M. Miller, Et Al

Open Access Publications

No abstract provided.

Phenotype Of Peripheral Nk Cells In Latent, Active, And Meningeal Tuberculosis, José Alberto Choreño-Parra, Shabaana A. Khader, Et Al

Open Access Publications

No abstract provided.

A Microbiota-Directed Food Intervention For Undernourished Children, Robert Y Chen, Matthew C Hibberd, Arjun S Raman, Daniel Webber, Cyrus Zhou, Vinaik Sundaresan, Kazi Ahsan, Martin F Meier, Michael J Barratt, Jeffrey I Gordon, Et Al

Open Access Publications

BACKGROUND: More than 30 million children worldwide have moderate acute malnutrition. Current treatments have limited effectiveness, and much remains unknown about the pathogenesis of this condition. Children with moderate acute malnutrition have perturbed development of their gut microbiota.

METHODS: In this study, we provided a microbiota-directed complementary food prototype (MDCF-2) or a ready-to-use supplementary food (RUSF) to 123 slum-dwelling Bangladeshi children with moderate acute malnutrition between the ages of 12 months and 18 months. The supplementation was given twice daily for 3 months, followed by 1 month of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age z scores and mid-upper-arm circumference …

Integrating Neuroimaging Biomarkers Into The Multicentre, High-Dose Erythropoietin For Asphyxia And Encephalopathy (Heal) Trial: Rationale, Protocol And Harmonisation, Jessica L Wisnowski, Robert C Mckinstry, Et Al

Open Access Publications

INTRODUCTION: MRI and MR spectroscopy (MRS) provide early biomarkers of brain injury and treatment response in neonates with hypoxic-ischaemic encephalopathy). Still, there are challenges to incorporating neuroimaging biomarkers into multisite randomised controlled trials. In this paper, we provide the rationale for incorporating MRI and MRS biomarkers into the multisite, phase III high-dose erythropoietin for asphyxia and encephalopathy (HEAL) Trial, the MRI/S protocol and describe the strategies used for harmonisation across multiple MRI platforms.

METHODS AND ANALYSIS: Neonates with moderate or severe encephalopathy enrolled in the multisite HEAL trial undergo MRI and MRS between 96 and 144 hours of age using …