Medicine and Health Sciences Commons^™

Treatment De-Escalation For Hpv-Associated Oropharyngeal Squamous Cell Carcinoma With Radiotherapy Vs. Trans-Oral Surgery (Orator2): Study Protocol For A Randomized Phase Ii Trial., Anthony C Nichols, Pencilla Lang, Eitan Prisman, Eric Berthelet, Eric Tran, Sarah Hamilton, Jonn Wu, Kevin Fung, John R De Almeida, Andrew Bayley, David P Goldstein, Antoine Eskander, Zain Husain, Houda Bahig, Apostolos Christopoulous, Michael Hier, Khalil Sultanem, Keith Richardson, Alex Mlynarek, Suren Krishnan, Hien Le, John Yoo, S Danielle Macneil, Adrian Mendez, Eric Winquist, Nancy Read, Varagur Venkatesan, Sara Kuruvilla, Andrew Warner, Sylvia Mitchell, Martin Corsten, Murali Rajaraman, Stephanie Johnson-Obaseki, Libni Eapen, Michael Odell, Shamir Chandarana, Robyn Banerjee, Joseph Dort, T Wayne Matthews, Robert Hart, Paul Kerr, Samuel Dowthwaite, Michael Gupta, Han Zhang, Jim Wright, Christina Parker, Bret Wehrli, Keith Kwan, Julie Theurer, David A Palma

Paediatrics Publications

BACKGROUND: Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches. …

A Ten-Year Retrospective Evaluation Of Acute Flaccid Myelitis At 5 Pediatric Centers In The United States, 2005-2014., Margaret M. Cortese, Anita K. Kambhampati, Jennifer E. Schuster, Zaid Alhinai, Gary R. Nelson, Gloria J. Guzman Perez-Carrillo, Arastoo Vossough, Michael A. Smit, Robert C. Mckinstry, Timothy Zinkus, Kevin R. Moore, Jeffrey M. Rogg, Meghan S. Candee, James J. Sejvar, Sarah E. Hopkins

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Acute flaccid myelitis (AFM) is a severe illness similar to paralytic poliomyelitis. It is unclear how frequently AFM occurred in U.S. children after poliovirus elimination. In 2014, an AFM cluster was identified in Colorado, prompting passive US surveillance that yielded 120 AFM cases of unconfirmed etiology. Subsequently, increased reports were received in 2016 and 2018. To help inform investigations on causality of the recent AFM outbreaks, our objective was to determine how frequently AFM had occurred before 2014, and if 2014 cases had different characteristics.

METHODS: We conducted a retrospective study covering 2005-2014 at 5 pediatric centers in 3 …

Global Longitudinal Strain And Cardiac Events In Patients With Immune Checkpoint Inhibitor-Related Myocarditis., Magid Awadalla, Syed S Mahmood, John D Groarke, Malek Z O Hassan, Anju Nohria, Adam Rokicki, Sean P Murphy, Nathaniel D Mercaldo, Lili Zhang, Daniel A Zlotoff, Kerry L Reynolds, Raza M Alvi, Dahlia Banerji, Shiying Liu, Lucie M Heinzerling, Maeve Jones-O'Connor, Rula B Bakar, Justine V Cohen, Michael C Kirchberger, Ryan J Sullivan, Dipti Gupta, Connor P Mulligan, Sachin P Shah, Sarju Ganatra, Muhammad A. Rizvi Md, Gagan Sahni, Carlo G Tocchetti, Donald P Lawrence, Michael Mahmoudi, Richard B Devereux, Brian J Forrestal, Anant Mandawat, Alexander R Lyon, Carol L Chen, Ana Barac, Judy Hung, Paaladinesh Thavendiranathan, Michael H Picard, Franck Thuny, Stephane Ederhy, Michael G Fradley, Tomas G Neilan

Department of Medicine

BACKGROUND: There is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving standard chemotherapy. There are no data on the use of GLS in ICI myocarditis.

OBJECTIVES: This study sought to evaluate the role of GLS and assess its association with cardiac events among patients with ICI myocarditis.

METHODS: This study retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI myocarditis (cases, n = 101) to that from patients receiving an ICI who did not …

A Broad-Spectrum Antiviral Molecule, Ql47, Selectively Inhibits Eukaryotic Translation, Mélissanne De Wispelaere, Margot Carocci, Dominique J Burri, William J Neidermyer, Calla M Olson, Imme Roggenbach, Yanke Liang, Jinhua Wang, Sean P J Whelan, Nathanael S Gray, Priscilla L Yang

Faculty, Staff and Students Publications

Small-molecule inhibitors of translation are critical tools to study the molecular mechanisms of protein synthesis. In this study, we sought to characterize how QL47, a host-targeted, small-molecule antiviral agent, inhibits steady-state viral protein expression. We demonstrate that this small molecule broadly inhibits both viral and host protein synthesis and targets a translation step specific to eukaryotic cells. We show that QL47 inhibits protein neosynthesis initiated by both canonical cap-driven and noncanonical initiation strategies, most likely by targeting an early step in translation elongation. Our findings thus establish QL47 as a new small-molecule inhibitor that can be utilized to probe the …

Association Of Time-Varying Blood Pressure With Chronic Kidney Disease Progression In Children., Ben Christopher Reynolds, Jennifer Lynn Roem, Derek Kai Sing Ng, Mina Matsuda-Abedini, Joseph Thomas Flynn, Susan Lynn Furth, Bradley A. Warady, Rulan Savita Parekh

Manuscripts, Articles, Book Chapters and Other Papers

Importance: Optimal blood pressure (BP) management in children with chronic kidney disease (CKD) slows progression to end-stage renal disease. Studies often base progression risk on a single baseline BP measurement, which may underestimate risk.

Objective: To determine whether time-varying BP measurements are associated with a higher risk of progression of CKD than baseline BP measurements.

Design, Setting, and Participants: The ongoing longitudinal, prospective cohort study Chronic Kidney Disease in Children (CKID) recruited children from January 19, 2005, through March 19, 2014, from pediatric nephrology centers across North America, with data collected at annual study visits. Participants included children aged 1 …

The Role Of Noninvasive Tests For Differentiating Nash From Nafl And Diagnosing Advanced Fibrosis Among Patients With Nafld, Maya Balakrishnan, Rohit Loomba

Faculty, Staff and Students Publications

Assessing for the presence of non-alcoholic steatohepatitis (NASH) and the presence of advanced fibrosis is vital among patients with non-alcoholic fatty liver disease (NAFLD) as each is predictive of disease outcomes. A liver biopsy is the gold standard method for doing so but is impossible to perform among all patients with NAFLD. Reliable methods for noninvasively detecting for the presence of NASH and advanced fibrosis are thus a pressing need. The search for noninvasive tests has been more successful for advanced fibrosis than for NASH. Clinical prediction models and elastography have acceptable accuracy for ruling out advanced fibrosis; when used …

De Novo Mutations Across 1,465 Diverse Genomes Reveal Mutational Insights And Reductions In The Amish Founder Population, Michael D Kessler, Douglas P Loesch, James A Perry, Nancy L Heard-Costa, Daniel Taliun, Brian E Cade, Heming Wang, Michelle Daya, John Ziniti, Soma Datta, Juan C Celedón, Manuel E Soto-Quiros, Lydiana Avila, Scott T Weiss, Kathleen Barnes, Susan S Redline, Ramachandran S Vasan, Andrew D Johnson, Rasika A Mathias, Ryan Hernandez, James G Wilson, Deborah A Nickerson, Goncalo Abecasis, Sharon R Browning, Sebastian Zöllner, Jeffrey R O'Connell, Braxton D Mitchell, Timothy D O'Connor

Faculty, Staff and Student Publications

De novo mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole-genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) Program, we called 93,325 single-nucleotide DNMs across 1,465 trios from an array of diverse human populations, and used them to directly estimate and analyze DNM counts, rates, and spectra. We find a significant positive correlation between local recombination rate and local DNM rate, and that DNM rate explains a …

Patients' Perspectives Of Tuberculosis Treatment Challenges And Barriers To Treatment Adherence In Ukraine: A Qualitative Study, Omowunmi Aibana, Emily Dauria, Tetiana Kiriazova, Olena Makarenko, Mariya Bachmaha, Natasha Rybak, Timothy Palen Flanigan, Vasyl Petrenko, Anne E Becker, Megan B Murray

Faculty, Staff and Student Publications

OBJECTIVES: To understand the challenges faced by patients with tuberculosis (TB) and factors that influence TB treatment adherence in Ukraine.

DESIGN: Qualitative study.

SETTING: TB treatment facilities in Kyiv Oblast, Ukraine.

PARTICIPANTS: Sixty adults who had undergone treatment for drug-sensitive TB between June 2012 and August 2015.

METHODS: We conducted semistructured, in-depth, individual interviews among a purposively selected clinical sample of patients previously treated for drug-sensitive TB. Interview content encompassed WHO's framework for barriers to adherence to long-term therapies and included questions about patient preferences and motivators concerning treatment adherence. We examined treatment experience across strata defined by previously identified …

Insights Image For "Evidence Of Increased Hypoxia Signalling In Fetal Liver From Maternal Nutrient Restriction In Mice"., Bethany N Radford, Victor K M Han

Paediatrics Publications

No abstract provided.

Reactive Stepping After A Forward Fall In People Living With Incomplete Spinal Cord Injury Or Disease, Katherine Chan, Jae Woung Lee, Janelle Unger, Jaeeun Yoo, Kei Masani, Kristin E Musselman

Physical Therapy Publications

STUDY DESIGN: Cross sectional.

OBJECTIVES: To compare the reactive stepping ability of individuals living with incomplete spinal cord injury or disease (SCI/D) to that of sex- and age-matched able-bodied adults.

SETTING: A tertiary SCI/D rehabilitation center in Canada.

METHODS: Thirty-three individuals (20 with incomplete SCI/D) participated. Participants assumed a forward lean position in standing whilst 8-12% of their body weight was supported by a horizontal cable at waist height affixed to a rigid structure. The cable was released unexpectedly, simulating a forward fall and eliciting one or more reactive steps. Behavioral responses (i.e., single step versus non-single step) were compared …

Safety And Immunogenicity Of The Oral, Inactivated, Enterotoxigenic Escherichia Coli Vaccine Etvax In Bangladeshi Children And Infants: A Double-Blind, Randomised, Placebo-Controlled Phase 1/2 Trial, Firdausi Qadri, Marjahan Akhtar, Taufiqur R Bhuiyan, Mohiul I Chowdhury, Tasnuva Ahmed, Tanzeem A Rafique, Arifuzzaman Khan, Sadia I A Rahman, Farhana Khanam, Anna Lundgren, Gudrun Wiklund, Joanna Kaim, Madeleine Löfstrand, Nils Carlin, A Louis Bourgeois, Nicole Maier, Alan Fix, Thomas Wierzba, Richard I Walker, Ann-Mari Svennerholm

Faculty and Staff Publications

Background: Enterotoxigenic Escherichia coli causes diarrhoea, leading to substantial mortality and morbidity in children, but no specific vaccine exists. This trial tested an oral, inactivated, enterotoxigenic E coli vaccine (ETVAX), which has been previously shown to be safe and highly immuongenic in Swedish and Bangladeshi adults. We tested the safety and immunogenicity of ETVAX, consisting of four E coli strains overexpressing the most prevalent colonisation factors (CFA/I, CS3, CS5, and CS6) and a toxoid (LCTBA) administered with or without a double-mutant heat-labile enterotoxin (dmLT) as an adjuvant, in Bangladeshi children.

Methods: We did a randomised, double-blind, placebo-controlled, dose-escalation, age-descending, phase …

Final Two-Year Outcomes For The Sentry Bioconvertible Inferior Vena Cava Filter In Patients Requiring Temporary Protection From Pulmonary Embolism., Michael D Dake, Timothy P Murphy, Albrecht H Krämer, Michael D Darcy, Luke E Sewall, Michael A Curi, Matthew S Johnson, Frank Arena, James L Swischuk, Gary M Ansel, Mitchell J Silver, Souheil Saddekni, Jayson S Brower, Robert Mendes, Sentry Trial Investigators

Heart and Vascular Articles

PURPOSE: To report final 2-year outcomes with the Sentry bioconvertible inferior vena cava (IVC) filter in patients requiring temporary protection against pulmonary embolism (PE).

MATERIALS AND METHODS: In a prospective multicenter trial, the Sentry filter was implanted in 129 patients with documented deep vein thrombosis (DVT) and/or PE (67.5%) or who were at temporary risk of developing DVT/PE (32.6%). Patients were monitored and bioconversion status ascertained by radiography, computed tomography (CT), and CT venography through 2 years.

RESULTS: The composite primary 6-month endpoint of clinical success was achieved in 97.4% (111/114) of patients. The rate of new symptomatic PE was …

Age Of Acquisition Impacts The Brain Differently Depending On Neuroanatomical Metric, Hannah Claussenius-Kalman, Kelly A Vaughn, Pilar Archila-Suerte, Arturo E Hernandez

Faculty, Staff and Student Publications

Although researchers generally agree that a certain set of brain areas underlie bilingual language processing, there is discrepancy regarding what effect timing of language acquisition has on these regions. We aimed to investigate the neuroanatomical correlates of age of acquisition (AoA), which has been examined previously, but with inconsistent results, likely influenced by methodological differences across studies. We analyzed gray matter density, volume, and thickness using whole-brain linear models in 334 bilinguals and monolinguals. Neuroanatomical correlates of AoA differed depending on gray matter metric. Relative to early bilinguals, late bilinguals had thicker cortex in language processing and cognitive control regions, …

Toward Actionable Practice Parameters For "Dual Diagnosis": Principles Of Assessment And Management For Co-Occurring Psychiatric And Intellectual/Developmental Disability., John N. Constantino, Shae Strom, Michael Bunis, Cy Nadler, Teresa Rodgers, Julia Lepage, Connie Cahalan, Amber Stockreef, Lucas Evans, Rachel Jones, Alyssa Wilson

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE OF REVIEW: Although treatment algorithms and parameters for best practice are readily available for all major syndromes of psychiatric impairment, the occurrence of psychiatric syndromes in individuals with intellectual and developmental disability (IDD) invokes serious contextual challenges for interpretation of symptoms, diagnosis, and optimization of treatment, both for clinicians and for the service sectors in which care and support of individuals with IDD are delivered. Recognizing that there exist very few definitive resources for best practice under the circumstance of this form of "dual diagnosis," the Missouri Department of Mental Health convened an expert panel to conduct a focused …

Glopid-R Report On Chikungunya, O'Nyong-Nyong And Mayaro Virus, Part 5: Entomological Aspects, L. Pezzi, M. S. Diamond, Et Al.

2020-Current year OA Pubs

The GloPID-R (Global Research Collaboration for Infectious Disease Preparedness) chikungunya (CHIKV), o'nyong-nyong (ONNV) and Mayaro virus (MAYV) Working Group has been established to investigate natural history, epidemiology and clinical aspects of infection by these viruses. Here, we present a report dedicated to entomological aspects of CHIKV, ONNV and MAYV. Recent global expansion of chikungunya virus has been possible because CHIKV established a transmission cycle in urban settings using anthropophilic vectors such as Aedes albopictus and Aedes aegypti. MAYV and ONNV have a more limited geographic distribution, being confined to Africa (ONNV) and central-southern America (MAYV). ONNV is probably maintained through …

Diroximel Fumarate Demonstrates An Improved Gastrointestinal Tolerability Profile Compared With Dimethyl Fumarate In Patients With Relapsing-Remitting Multiple Sclerosis: Results From The Randomized, Double-Blind, Phase Iii Evolve-Ms-2 Study, Robert T Naismith, Et Al.

2020-Current year OA Pubs

BACKGROUND: Diroximel fumarate (DRF) is a novel oral fumarate approved in the USA for relapsing forms of multiple sclerosis. DRF is converted to monomethyl fumarate, the pharmacologically active metabolite of dimethyl fumarate (DMF). DRF 462 mg and DMF 240 mg produce bioequivalent exposure of monomethyl fumarate and are therefore expected to have similar efficacy/safety profiles; the distinct chemical structure of DRF may contribute to its tolerability profile.

OBJECTIVES: The objective of this study was to compare the gastrointestinal tolerability of DRF and DMF over 5 weeks in patients with relapsing-remitting multiple sclerosis.

METHODS: EVOLVE-MS-2 was a phase III, randomized, double-blind, …

Toward Actionable Practice Parameters For "Dual Diagnosis": Principles Of Assessment And Management For Co-Occurring Psychiatric And Intellectual/Developmental Disability, John N Constantino, Shae Strom, Michael Bunis, Cy Nadler, Teresa Rodgers, Julia Lepage, Connie Cahalan, Amber Stockreef, Lucas Evans, Rachel Jones, Alyssa Wilson

2020-Current year OA Pubs

PURPOSE OF REVIEW: Although treatment algorithms and parameters for best practice are readily available for all major syndromes of psychiatric impairment, the occurrence of psychiatric syndromes in individuals with intellectual and developmental disability (IDD) invokes serious contextual challenges for interpretation of symptoms, diagnosis, and optimization of treatment, both for clinicians and for the service sectors in which care and support of individuals with IDD are delivered. Recognizing that there exist very few definitive resources for best practice under the circumstance of this form of "dual diagnosis," the Missouri Department of Mental Health convened an expert panel to conduct a focused …

Treatment Of Atopic Dermatitis With Ruxolitinib Cream (Jak1/Jak2 Inhibitor) Or Triamcinolone Cream, Brian S Kim, Michael D Howell, Kang Sun, Kim Papp, Adnan Nasir, Michael E Kuligowski, Incb 18424-206 Study Investigators

2020-Current year OA Pubs

BACKGROUND: Atopic dermatitis (AD) is a highly pruritic chronic inflammatory skin disorder. Ruxolitinib, a selective inhibitor of Janus kinase 1 and Janus kinase 2, potently suppresses cytokine signaling involved in AD pathogenesis.

OBJECTIVE: We sought to evaluate the efficacy and safety of ruxolitinib (RUX) cream in adults with AD.

METHODS: In this phase 2 study (NCT03011892), 307 adult patients with AD, an Investigator's Global Assessment score of 2 or 3 (mild or moderate), and 3% to 20% affected body surface area were equally randomized for 8 weeks of double-blind treatment to RUX (1.5% twice daily [BID], 1.5% once daily [QD], …

A Set Of Functionally-Defined Brain Regions With Improved Representation Of The Subcortex And Cerebellum, Benjamin A Seitzman, Caterina Gratton, Scott Marek, Ryan V Raut, Nico U F Dosenbach, Bradley L Schlaggar, Steven E Petersen, Deanna J Greene

2020-Current year OA Pubs

An important aspect of network-based analysis is robust node definition. This issue is critical for functional brain network analyses, as poor node choice can lead to spurious findings and misleading inferences about functional brain organization. Two sets of functional brain nodes from our group are well represented in the literature: (1) 264 volumetric regions of interest (ROIs) reported in Power et al., 2011, and (2) 333 cortical surface parcels reported in Gordon et al., 2016. However, subcortical and cerebellar structures are either incompletely captured or missing from these ROI sets. Therefore, properties of functional network organization involving the subcortex and …

Contemporary Nstemi Management: The Role Of The Hospitalist., Charles V Pollack, Alpesh Amin, Tracy Wang, Steven Deitelzweig, Marc Cohen, David Slattery, John Fanikos, Christopher Dilascia, Regan Tuder, Scott Kaatz

Department of Emergency Medicine Faculty Papers

Non-ST-segment elevation myocardial infarction (NSTEMI) is defined as elevated cardiac biomarkers of necrosis in the absence of persistent ST-segment elevation in the setting of anginal symptoms or other acute event. It carries a poorer prognosis than most ST-segment elevation events, owing to the typical comorbidity burden of the older NSTEMI patients as well as diverse etiologies that add complexity to therapeutic decision-making. It may result from an acute atherothrombotic event ('Type 1') or as the result of other causes of mismatch of myocardial oxygen supply and demand ('Type 2'). Regardless of type and other clinical factors, the hospital medicine specialist …

Periodontal Inflammation: Integrating Genes And Dysbiosis, Shaoping Zhang, Ning Yu, Roger M Arce

Faculty, Staff and Student Publications

Biofilm bacteria co-evolve and reach a symbiosis with the host on the gingival surface. The disruption of the homeostatic relationship between plaque bacteria and the host can initiate and promote periodontal disease progression. Recent advances in sequencing technologies allow researchers to profile disease-associated microbial communities and quantify microbial metabolic activities and host transcriptional responses. In addition to confirming the findings from previous studies, new putative pathogens and novel genes that have not previously been associated with periodontitis, emerge. For example, multiple studies have reported that Synergistetes bacteria are associated with periodontitis. Genes involved in epithelial barrier defense were downregulated in …

Assessing Lymphatic Route Of Csf Outflow And Peripheral Lymphatic Contractile Activity During Head-Down Tilt Using Near-Infrared Fluorescence Imaging, John C Rasmussen, Sunkuk Kwon, Amanda Pinal, Alexander Bareis, Fred C Velasquez, Christopher F Janssen, John R Morrow, Caroline E Fife, Ron J Karni, Eva M Sevick-Muraca

Faculty, Staff and Student Publications

Evidence overwhelmingly suggests that the lymphatics play a critical role in the clearance of cerebrospinal fluid (CSF) from the cranial space. Impairment of CSF outflow into the lymphatics is associated with a number of pathological conditions including spaceflight-associated neuro-ocular syndrome (SANS), a problem that limits long-duration spaceflight. We used near-infrared fluorescence lymphatic imaging (NIRFLI) to dynamically visualize the deep lymphatic drainage pathways shared by CSF outflow and disrupted during head-down tilt (HDT), a method used to mimic the cephalad fluid shift that occurs in microgravity. After validating CSF clearance into the lymph nodes of the neck in swine, a pilot …

Everolimus-Induced Pneumonitis: A Diagnostic Challenge, Andrew Gulde, Elshad Hasanov, Kayla Krug, Gus W Krucke

Faculty, Staff and Student Publications

No abstract provided.

Diagnostic Criteria For Detection Of Retinal Nerve Fibre Layer Thickness And Neuroretinal Rim Width Abnormalities In Glaucoma, Feihui Zheng, Marco Yu, Christopher Kai-Shun Leung

Faculty, Staff and Student Publications

BACKGROUND/AIMS: Although measurements of the Bruch's membrane opening minimum rim width (BMO-MRW) and retinal nerve fibre layer thickness (RNFLT) with optical coherence tomography (OCT) have been widely adopted in the diagnostic evaluation of glaucoma, there is no consensus on the diagnostic criteria to define BMO-MRW and RNFLT abnormalities. This study investigated the sensitivities and specificities of different diagnostic criteria based on the OCT classification reports for detection of glaucoma.

METHODS: 340 eyes of 137 patients with glaucoma and 87 healthy individuals, all with axial length ≤26mm, had global and sectoral BMO-MRW and RNFLT measured with Spectralis OCT (Heidelberg Engineering). Six …

A Characterization Of Gaucher Ips-Derived Astrocytes: Potential Implications For Parkinson's Disease, Elma Aflaki, Barbara K Stubblefield, Ryan P Mcglinchey, Benjamin Mcmahon, Daniel S Ory, Ellen Sidransky

2020-Current year OA Pubs

While astrocytes, the most abundant cells found in the brain, have many diverse functions, their role in the lysosomal storage disorder Gaucher disease (GD) has not been explored. GD, resulting from the inherited deficiency of the enzyme glucocerebrosidase and subsequent accumulation of glucosylceramide and its acylated derivative glucosylsphingosine, has both non-neuronopathic (GD1) and neuronopathic forms (GD2 and 3). Furthermore, mutations in GBA1, the gene mutated in GD, are an important risk factor for Parkinson's disease (PD). To elucidate the role of astrocytes in the disease pathogenesis, we generated iAstrocytes from induced pluripotent stem cells made from fibroblasts taken from controls …

Redefining And Revisiting Cost Estimates Of Routine Art Care In Zambia: An Analysis Of Ten Clinics, Austin Tucker, Tannia Tembo, Radhika P Tampi, Jacob Mutale, Mpande Mukumba-Mwenechanya, Anjali Sharma, David W Dowdy, Carolyn B Moore, Elvin Geng, Charles B Holmes, Izukanji Sikazwe, Hojoon Sohn

2020-Current year OA Pubs

INTRODUCTION: Accurate costing is key for programme planning and policy implementation. Since 2011, there have been major changes in eligibility criteria and treatment regimens with price reductions in ART drugs, programmatic changes resulting in clinical task-shifting and decentralization of ART delivery to peripheral health centres making existing evidence on ART care costs in Zambia out-of-date. As decision makers consider further changes in ART service delivery, it is important to understand the current drivers of costs for ART care. This study provides updates on costs of ART services for HIV-positive patients in Zambia.

METHODS: We evaluated costs, assessed from the health …

Rationale And Design Of The Steroids To Reduce Systemic Inflammation After Infant Heart Surgery (Stress) Trial, Kevin D Hill, H Scott Baldwin, David P Bichel, Ryan J Butts, Reid C Chamberlain, Alicia M Ellis, Eric M Graham, Jesse Hickerson, Christoph P Hornik, Jeffrey P Jacobs, Marshall L Jacobs, Robert Db Jaquiss, Prince J Kannankeril, Sean M O'Brien, Rachel Torok, Joseph W Turek, Jennifer S Li, Stress Network Investigators

Faculty, Staff and Students Publications

For decades, physicians have administered corticosteroids in the perioperative period to infants undergoing heart surgery with cardiopulmonary bypass (CPB) to reduce the postoperative systemic inflammatory response to CPB. Some question this practice because steroid efficacy has not been conclusively demonstrated and because some studies indicate that steroids could have harmful effects. STRESS is a randomized, placebo-controlled, double-blind, multicenter trial designed to evaluate safety and efficacy of perioperative steroids in infants (age < 1 year) undergoing heart surgery with CPB. Participants (planned enrollment = 1,200) are randomized 1:1 to methylprednisolone (30 mg/kg) administered into the CPB pump prime versus placebo. The trial is nested within the existing infrastructure of the Society of Thoracic Surgeons Congenital Heart Surgery Database. The primary outcome is a global rank score of mortality, major morbidities, and hospital length of stay with components ranked commensurate with their clinical severity. Secondary outcomes include several measures of major postoperative morbidity, postoperative hospital length of stay, and steroid-related safety outcomes including prevalence of hyperglycemia and postoperative infectious complications. STRESS will be one of the largest trials ever conducted in children with heart disease and will answer a decades-old question related to safety and efficacy of perioperative steroids in infants undergoing heart surgery with CPB. The pragmatic "trial within a registry" design may provide a mechanism for conducting low-cost, high-efficiency trials in a heretofore-understudied patient population.

Benefit Of Contact Force-Guided Catheter Ablation For Treating Premature Ventricular Contractions, Ziming Zhao, Xiaowei Liu, Lianjun Gao, Yutao Xi, Qi Chen, Dong Chang, Xianjie Xiao, Jie Cheng, Yanzong Yang, Yunlong Xia, Xiaomeng Yin

The Texas Heart Institute Journal

We evaluated whether an irrigated contact force–sensing catheter would improve the safety and effectiveness of radiofrequency ablation of premature ventricular contractions originating from the right ventricular outflow tract.

We retrospectively reviewed the charts of patients with symptomatic premature ventricular contractions who underwent ablation with a contact force–sensing catheter (56 patients, SmartTouch) or conventional catheter (59 patients, ThermoCool) at our hospital from August 2013 through December 2015. During a mean follow-up of 16 ± 5 months, 3 patients in the conventional group had recurrences, compared with none in the contact force group. Complications occurred only in the conventional group (one steam …

Unusual Cause Of Heart Failure In A Patient With Marfan Syndrome: A Late Complication Of Bioprosthetic Valved Graft Replacement, Prerna B Bansal, Hari P Chaliki, Kantha R Kolla, Roger L Click, Alberto Pochettino

The Texas Heart Institute Journal

A high-velocity gradient across the left ventricular outflow tract is most often caused by aortic valve stenosis. We describe the unusual case of a high-velocity gradient caused by a kinked ascending aortic graft in a 69-year-old man who had Marfan syndrome. The patient had a history of ascending aortic aneurysm and had previously undergone replacement of the aortic root and ascending aorta with use of a bioprosthetic valved graft. The kinking was caused by dilation of the native aortic arch. The patient underwent successful hemi-arch replacement and repair of the kinked graft. Late complications and reoperation after proximal aortic surgery …

Obstruction Of 2 Coronary Arteries From Different Causes Immediately After Transapical Transcatheter Aortic Valve Replacement, Umihiko Kaneko, Ryuji Koshima, Hirosato Doi, Tsutomu Fujita

The Texas Heart Institute Journal

Coronary obstruction, a rare complication of transcatheter aortic valve replacement, can be fatal. Few data exist on this phenomenon, and, to date, authors have reported only single coronary lesions. We present a case in which 2 coronary arteries obstructed immediately after transapical transcatheter aortic valve replacement. The patient was an 81-year-old woman with symptomatic severe aortic stenosis who underwent transapical transcatheter aortic valve replacement. Immediately after an Edwards Sapien XT valve was deployed, she experienced sudden cardiogenic shock resulting from obstruction of the left main coronary artery ostium and the distal left anterior descending coronary artery. The left main obstruction …