“Harmonization of large MRI datasets for the analysis of brain imaging patterns throughout the lifespan” (2020) NeuroImage
Harmonization of large MRI datasets for the analysis of brain imaging patterns throughout the lifespan
(2020) NeuroImage, 208, art. no. 116450, .
Pomponio, R.a , Erus, G.a , Habes, M.a b , Doshi, J.a , Srinivasan, D.a , Mamourian, E.a , Bashyam, V.a , Nasrallah, I.M.a g , Satterthwaite, T.D.l , Fan, Y.a , Launer, L.J.c , Masters, C.L.d , Maruff, P.d , Zhuo, C.e f , Völzke, H.h , Johnson, S.C.i , Fripp, J.j , Koutsouleris, N.k , Wolf, D.H.l , Gur, R.g l , Gur, R.g l , Morris, J.m , Albert, M.S.n , Grabe, H.J.o , Resnick, S.M.p , Bryan, R.N.q , Wolk, D.A.b , Shinohara, R.T.a r s , Shou, H.a r , Davatzikos, C.a
a Center for Biomedical Image Computing and Analytics, Department of Radiology, University of Pennsylvania, United States
b Department of Neurology, University of Pennsylvania, United States
c Laboratory of Epidemiology and Population Sciences, National Institute on Aging, United States
d Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia
e Tianjin Mental Health Center, Nankai University Affiliated Tianjin Anding Hospital, Tianjin, China
f Department of Psychiatry, Tianjin Medical University, Tianjin, China
g Department of Radiology, University of Pennsylvania, United States
h Institute for Community Medicine, University of Greifswald, Germany
i Wisconsin Alzheimer’s Institute, University of Wisconsin School of Medicine and Public Health, United States
j CSIRO Health and Biosecurity, Australian e-Health Research Centre CSIRO, Australia
k Department of Psychiatry and Psychotherapy, Ludwig Maximilian University of Munich, Germany
l Department of Psychiatry, University of Pennsylvania, United States
m Department of Neurology, Washington University in St. Louis, United States
n Department of Neurology, Johns Hopkins University School of Medicine, United States
o Department of Psychiatry and Psychotherapy, Ernst-Moritz-Arndt University, Germany
p Laboratory of Behavioral Neuroscience, National Institute on Aging, United States
q Department of Diagnostic Medicine, University of Texas at Austin, United States
r Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, United States
s Penn Statistics in Imaging and Visualization Center, Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, United States
Abstract
As medical imaging enters its information era and presents rapidly increasing needs for big data analytics, robust pooling and harmonization of imaging data across diverse cohorts with varying acquisition protocols have become critical. We describe a comprehensive effort that merges and harmonizes a large-scale dataset of 10,477 structural brain MRI scans from participants without a known neurological or psychiatric disorder from 18 different studies that represent geographic diversity. We use this dataset and multi-atlas-based image processing methods to obtain a hierarchical partition of the brain from larger anatomical regions to individual cortical and deep structures and derive age trends of brain structure through the lifespan (3–96 years old). Critically, we present and validate a methodology for harmonizing this pooled dataset in the presence of nonlinear age trends. We provide a web-based visualization interface to generate and present the resulting age trends, enabling future studies of brain structure to compare their data with this reference of brain development and aging, and to examine deviations from ranges, potentially related to disease. © 2019 The Authors
Author Keywords
Brain; FreeSurfer; MRI; MUSE; ROI; Segmentation
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Correction of respiratory artifacts in MRI head motion estimates” (2020) NeuroImage
Correction of respiratory artifacts in MRI head motion estimates
(2020) NeuroImage, 208, art. no. 116400, .
Fair, D.A.a b c , Miranda-Dominguez, O.a , Snyder, A.Z.d e , Perrone, A.a , Earl, E.A.a , Van, A.N.f , Koller, J.M.g , Feczko, E.a h , Tisdall, M.D.i , van der Kouwe, A.j , Klein, R.L.b , Mirro, A.E.d k , Hampton, J.M.g , Adeyemo, B.d , Laumann, T.O.g , Gratton, C.l , Greene, D.J.e g , Schlaggar, B.L.m u v , Hagler, D.J., Jr.n , Watts, R.o , Garavan, H.p , Barch, D.M.e g q , Nigg, J.T.a b , Petersen, S.E.d e f q r , Dale, A.M.n s , Feldstein-Ewing, S.W.b , Nagel, B.J.a b , Dosenbach, N.U.F.d e f k t
a Department of Behavioral Neuroscience, Oregon Health & Sciences University, Portland, OR, United States
b Department of Psychiatry, Oregon Health & Sciences University, Portland, OR, United States
c Advanced Imaging Research Center, Oregon Health & Sciences University, Portland, OR, United States
d Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
e Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
f Department of Biomedical Engineering, Washington University, St. Louis, MO, United States
g Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
h Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Sciences University, Portland, OR, United States
i Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
j Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, United States
k Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
l Department of Psychology & Neurology, Northwestern University, Chicago, IL, United States
m Kennedy Krieger Institute, Baltimore, MD, United States
n Department of Radiology, University of California San Diego, La Jolla, CA, United States
o Department of Psychology, Yale University, New Haven, CT, United States
p Department of Psychiatry, University of Vermont, Burlington, VT, United States
q Department of Psychological & Brain Sciences, Washington University, St. Louis, MO, United States
r Department of Neuroscience, Washington University, St. Louis, MO, United States
s Department of Neurosciences, University of California San Diego, La Jolla, CA, United States
t Program in Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United States
u Department of Neurology, Johns Hopkins University, Baltimore, MD, United States
v Department of Pediatrics, Johns Hopkins University, Baltimore, MD, United States
Abstract
Head motion represents one of the greatest technical obstacles in magnetic resonance imaging (MRI) of the human brain. Accurate detection of artifacts induced by head motion requires precise estimation of movement. However, head motion estimates may be corrupted by artifacts due to magnetic main field fluctuations generated by body motion. In the current report, we examine head motion estimation in multiband resting state functional connectivity MRI (rs-fcMRI) data from the Adolescent Brain and Cognitive Development (ABCD) Study and comparison ‘single-shot’ datasets. We show that respirations contaminate movement estimates in functional MRI and that respiration generates apparent head motion not associated with functional MRI quality reductions. We have developed a novel approach using a band-stop filter that accurately removes these respiratory effects from motion estimates. Subsequently, we demonstrate that utilizing a band-stop filter improves post-processing fMRI data quality. Lastly, we demonstrate the real-time implementation of motion estimate filtering in our FIRMM (Framewise Integrated Real-Time MRI Monitoring) software package. © 2019 The Authors
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Sex may influence motor phenotype in a novel rodent model of cerebral palsy” (2020) Neurobiology of Disease
Sex may influence motor phenotype in a novel rodent model of cerebral palsy
(2020) Neurobiology of Disease, 134, art. no. 104711, .
Aravamuthan, B.R.a b c , Gandham, S.a , Young, A.B.c d , Rutkove, S.B.c e
a Washington University in St. Louis School of Medicine, St. Louis, MO, United States
b Boston Children’s Hospital, Boston, MA, United States
c Harvard Medical School, Boston, MA, United States
d Massachusetts General Hospital, Boston, MA, United States
e Beth Israel Deaconess Medical Center, Boston, MA, United States
Abstract
Cerebral palsy (CP) is the most common cause of childhood motor disability, manifesting most often as spasticity and/or dystonia. Spasticity and dystonia are often co-morbid clinically following severe injury at term gestation. Currently available animal CP models have not demonstrated or differentiated between these two motor phenotypes, limiting their clinical relevance. We sought to develop an animal CP model displaying objectively identifiable spasticity and dystonia. We exposed rat pups at post-natal day 7–8 (equivalent to human 37 post-conceptional weeks) to global hypoxia. Since spasticity and dystonia can be difficult to differentiate from each other in CP, objective electrophysiologic markers of motor phenotypes were assessed. Spasticity was inferred using an electrophysiologic measure of hyperreflexia: soleus Hoffman reflex suppression with 2 Hz tibial nerve stimulation. Dystonia was assessed during voluntary isometric hindlimb withdrawal at different levels of arousal by calculating tibialis anterior and triceps surae electromyographic co-activation as a surrogate of overflow muscle activity. Hypoxia affected spasticity and dystonia measures in a sex-dependent manner. Males had attenuated Hoffman reflex suppression suggestive of spasticity but no change in antagonist muscle co-activation. In contrast, females demonstrated increased co-activation suggestive of dystonia but no change in Hoffman reflex suppression. Therefore, there was an unexpected segregation of electrophysiologically-defined motor phenotypes based on sex with males predominantly demonstrating spasticity and females predominantly demonstrating dystonia. These results require human clinical confirmation but suggest that sex could play a critical role in the motor manifestations of neonatal brain injury. © 2019
Author Keywords
Animal models of disease; Cerebral palsy; Dystonia; Neonatal brain injury; Spasticity
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Early Detection of Endolymphatic Hydrops using the Auditory Nerve Overlapped Waveform (ANOW)” (2020) Neuroscience
Early Detection of Endolymphatic Hydrops using the Auditory Nerve Overlapped Waveform (ANOW)
(2020) Neuroscience, 425, pp. 251-266.
Lee, C.a , Valenzuela, C.V.a , Goodman, S.S.b , Kallogjeri, D.a , Buchman, C.A.a , Lichtenhan, J.T.a
a Washington University School of Medicine in St. Louis, Department of Otolaryngology, Saint Louis, MO, United States
b University of Iowa, Department of Communication Sciences and Disorders, Iowa City, IA, United States
Abstract
Endolymphatic hydrops is associated with low-frequency sensorineural hearing loss, with a large body of research dedicated to examining its putative causal role in low-frequency hearing loss. Investigations have been thwarted by the fact that hearing loss is measured in intact ears, but gold standard assessments of endolymphatic hydrops are made postmortem only; and that no objective low-frequency hearing measure has existed. Yet the association of endolymphatic hydrops with low-frequency hearing loss is so strong that it has been established as one of the important defining features for Ménière’s disease, rendering it critical to detect endolymphatic hydrops early, regardless of whether it serves a causal role or is the result of other disease mechanisms. We surgically induced endolymphatic hydrops in guinea pigs and employed our recently developed objective neural measure of low-frequency hearing, the Auditory Nerve Overlapped Waveform (ANOW). Hearing loss and endolymphatic hydrops were assessed at various time points after surgery. The ANOW detected low-frequency hearing loss as early as the first day after surgery, well before endolymphatic hydrops was found histologically. The ANOW detected low-frequency hearing loss with perfect sensitivity and specificity in all ears after endolymphatic hydrops developed, where there was a strong linear relationship between degree of endolymphatic hydrops and severity of low-frequency hearing loss. Further, histological data demonstrated that endolymphatic hydrops is seen first in the high-frequency cochlear base, though the ANOW demonstrated that dysfunction begins in the low-frequency apical cochlear half. The results lay the groundwork for future investigations of the causal role of endolymphatic hydrops in low-frequency hearing loss. © 2019 IBRO
Author Keywords
cochlea; cochlear action potential; compound action potential; low frequency hearing; Ménière’s disease; otoacoustic emissions
Document Type: Article
Publication Stage: Final
Source: Scopus
“BOLD-MRI demonstrates acute placental and fetal organ hypoperfusion with fetal brain sparing in response to phenylephrine but not ephedrine” (2020) Placenta
BOLD-MRI demonstrates acute placental and fetal organ hypoperfusion with fetal brain sparing in response to phenylephrine but not ephedrine
(2020) Placenta, 90, pp. 52-57.
Shapiro, J.a , Ginosar, Y.a b c , Gielchinsky, Y.d , Elchalal, U.d , Bromberg, Z.e , Corchia-Nachmanson, N.c e , Abramovitch, R.c e
a Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, Ein Karem, Jerusalem, Israel
b Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, United States
c Wohl Institute of Translational Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel
d Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center, Ein Karem, Jerusalem, Israel
e The Goldyne Savad Institute of Gene Therapy and MRI Laboratory, Hadassah Hebrew University Medical Center, Ein Karem, Jerusalem, Israel
Abstract
Introduction: We previously reported blood oxygen level dependent MRI (BOLD-MRI) for monitoring placental and fetal hemodynamic changes in mice following maternal hypercapnia. Here we use BOLD-MRI to compare the placental and fetal hemodynamic effects of different maternal vasopressors in mice. Methods: Pregnant ICR mice (n = 16; E17.5) anesthetized with pentobarbital (80 mg/kg i.p.) were placed supine in a 4.7-T Bruker Biospec MRI. Following baseline images, equipotential doses of ephedrine (10 mg/kg) or phenylephrine (10mcg/kg) were administered intravenously. Changes in placental and fetal signal were analyzed from T2*-weighted gradient echo MR images (TR/TE = 147/10 ms). Different regions of interest (placenta, fetal heart, fetal liver and fetal brain) were identified. Percentage change of BOLD-MRI signal intensity (SI) were presented as time curves. Results: Ephedrine and phenylephrine elicited markedly different effects. Phenylephrine caused an approximate 50% reduction in placental, fetal heart and fetal liver BOLD-MRI-SI, but fetal brain BOLD-MRI-SI was unchanged (statistically different from placenta and other fetal organs; p < 0.001), and the fetal brain/liver BOLD-MRI-SI ratio was markedly increased versus baseline (p < 0.001). Following ephedrine, placental BOLD-MRI-SI increased 30% and fetal heart BOLD-MRI-SI was reduced 26%; other fetal organs were unchanged. Blood gases were unchanged. Discussion: Phenylephrine induced BOLD-MRI-SI changes suggestive of placental and fetal hypoperfusion with brain sparing. Ephedrine induced BOLD-MRI-SI changes suggestive of increased cardiac output; we speculate that reduced fetal heart BOLD-MRI-SI may be due to increased fetal myocardial oxygen extraction or metabolic acidosis. The result demonstrates the potential of BOLD-MRI as a non-invasive hemodynamic tool for assessing pharmacodynamics effects in the placental and fetus. © 2019
Author Keywords
Animal models; Functional MRI; Pharmacodynamics; Placental blood flow; Vasopressors
Document Type: Article
Publication Stage: Final
Source: Scopus
“Atomistic basis of opening and conduction in mammalian inward rectifier potassium (Kir2.2) channels” (2020) The Journal of General Physiology
Atomistic basis of opening and conduction in mammalian inward rectifier potassium (Kir2.2) channels
(2020) The Journal of General Physiology, 152 (1), .
Zangerl-Plessl, E.-M.a , Lee, S.-J.b , Maksaev, G.b , Bernsteiner, H.a , Ren, F.b , Yuan, P.b , Stary-Weinzinger, A.a , Nichols, C.G.b
a Department of Pharmacology and Toxicology, University of ViennaVienna, Austria
b Department of Cell Biology and Physiology and the Center for Investigation of Membrane Excitability Diseases, Washington University School of Medicine, St. Louis, MO
Abstract
Potassium ion conduction through open potassium channels is essential to control of membrane potentials in all cells. To elucidate the open conformation and hence the mechanism of K+ ion conduction in the classic inward rectifier Kir2.2, we introduced a negative charge (G178D) at the crossing point of the inner helix bundle, the location of ligand-dependent gating. This “forced open” mutation generated channels that were active even in the complete absence of phosphatidylinositol-4,5-bisphosphate (PIP2), an otherwise essential ligand for Kir channel opening. Crystal structures were obtained at a resolution of 3.6 Å without PIP2 bound, or 2.8 Å in complex with PIP2. The latter revealed a slight widening at the helix bundle crossing (HBC) through backbone movement. MD simulations showed that subsequent spontaneous wetting of the pore through the HBC gate region allowed K+ ion movement across the HBC and conduction through the channel. Further simulations reveal atomistic details of the opening process and highlight the role of pore-lining acidic residues in K+ conduction through Kir2 channels. © 2019 Zangerl-Plessl et al.
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Clinical Practice Guideline to Improve Locomotor Function Following Chronic Stroke, Incomplete Spinal Cord Injury, and Brain Injury” (2020) Journal of Neurologic Physical Therapy : JNPT
Clinical Practice Guideline to Improve Locomotor Function Following Chronic Stroke, Incomplete Spinal Cord Injury, and Brain Injury
(2020) Journal of Neurologic Physical Therapy : JNPT, 44 (1), pp. 49-100.
Hornby, T.G., Reisman, D.S., Ward, I.G., Scheets, P.L., Miller, A., Haddad, D., Fox, E.J., Fritz, N.E., Hawkins, K., Henderson, C.E., Hendron, K.L., Holleran, C.L., Lynskey, J.E., Walter, A., and the Locomotor CPG Appraisal Team
Department of Physical Medicine and Rehabilitation, Indiana University, Indianapolis (T.G.H., C.E.H.); Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, Illinois (T.G.H.); Department of Physical Therapy, University of Delaware, Newark (D.S.R., A.M.); Kessler Institute for Rehabilitation, West Orange, New Jersey (I.G.W., A.M., D.H.); Rutgers, New Jersey Medical School, Newark (I.G.W.); Infinity Rehab, Wilsonville, Oregon (P.L.S.); Department of Physical Therapy, University of Florida, Gainesville and Brooks Rehabilitation Center, Jacksonville, Florida (E.J.F., K.A.H.); Department of Physical Therapy, Wayne State University, Detroit, Michigan (N.E.F.); Sargent College of Health and Rehabilitation Sciences, Boston University, Boston, Massachusetts (K.L.H.); Program in Physical Therapy, Washington University in St Louis, St Louis, Missouri (C.L.H.); Department of Physical Therapy, A.T. Still University, Mesa, Arizona (J.V.L.); and Sheltering Arms Hospital, Mechanicsville, Virginia (A.W.)
Abstract
BACKGROUND: Individuals with acute-onset central nervous system (CNS) injury, including stroke, motor incomplete spinal cord injury, or traumatic brain injury, often experience lasting locomotor deficits, as quantified by decreases in gait speed and distance walked over a specific duration (timed distance). The goal of the present clinical practice guideline was to delineate the relative efficacy of various interventions to improve walking speed and timed distance in ambulatory individuals greater than 6 months following these specific diagnoses. METHODS: A systematic review of the literature published between 1995 and 2016 was performed in 4 databases for randomized controlled clinical trials focused on these specific patient populations, at least 6 months postinjury and with specific outcomes of walking speed and timed distance. For all studies, specific parameters of training interventions including frequency, intensity, time, and type were detailed as possible. Recommendations were determined on the basis of the strength of the evidence and the potential harm, risks, or costs of providing a specific training paradigm, particularly when another intervention may be available and can provide greater benefit. RESULTS: Strong evidence indicates that clinicians should offer walking training at moderate to high intensities or virtual reality-based training to ambulatory individuals greater than 6 months following acute-onset CNS injury to improve walking speed or distance. In contrast, weak evidence suggests that strength training, circuit (ie, combined) training or cycling training at moderate to high intensities, and virtual reality-based balance training may improve walking speed and distance in these patient groups. Finally, strong evidence suggests that body weight-supported treadmill training, robotic-assisted training, or sitting/standing balance training without virtual reality should not be performed to improve walking speed or distance in ambulatory individuals greater than 6 months following acute-onset CNS injury to improve walking speed or distance. DISCUSSION: The collective findings suggest that large amounts of task-specific (ie, locomotor) practice may be critical for improvements in walking function, although only at higher cardiovascular intensities or with augmented feedback to increase patient’s engagement. Lower-intensity walking interventions or impairment-based training strategies demonstrated equivocal or limited efficacy. LIMITATIONS: As walking speed and distance were primary outcomes, the research participants included in the studies walked without substantial physical assistance. This guideline may not apply to patients with limited ambulatory function, where provision of walking training may require substantial physical assistance. SUMMARY: The guideline suggests that task-specific walking training should be performed to improve walking speed and distance in those with acute-onset CNS injury although only at higher intensities or with augmented feedback. Future studies should clarify the potential utility of specific training parameters that lead to improved walking speed and distance in these populations in both chronic and subacute stages following injury. DISCLAIMER: These recommendations are intended as a guide for clinicians to optimize rehabilitation outcomes for persons with chronic stroke, incomplete spinal cord injury, and traumatic brain injury to improve walking speed and distance.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Editorial: On Collective Ownership of the Prevention of Mass Casualties Perpetrated by Youth” (2020) Journal of the American Academy of Child and Adolescent Psychiatry
Editorial: On Collective Ownership of the Prevention of Mass Casualties Perpetrated by Youth
(2020) Journal of the American Academy of Child and Adolescent Psychiatry, 59 (1), pp. 27-29.
Constantino, J.N.
Washington University School of Medicine, St. Louis, MO, United States
Abstract
A great deal has been learned in the aftermath of the Columbine High School massacre, and the science of prevention of mass casualties has matured over the past two decades. This article provides commentary on a new synthesis of the knowledge base, and incorporates very recent work from disparate disciplines that have further bearing on the prevention of such catastrophic events. Collective ownership of evidence-informed facets of primary, secondary, and tertiary prevention by all practicing child and adolescent psychiatrists–in concert with efforts of primary care physicians, educators, policy-makers, law enforcement, and the general public–stands to avert progression of at-risk youth through stages of violent radicalization and the acquisition of means to perpetrate these incidents. © 2019 American Academy of Child and Adolescent Psychiatry
Document Type: Editorial
Publication Stage: Final
Source: Scopus
“Dopamine D3 receptor: A neglected participant in Parkinson Disease pathogenesis and treatment?” (2020) Ageing Research Reviews
Dopamine D3 receptor: A neglected participant in Parkinson Disease pathogenesis and treatment?
(2020) Ageing Research Reviews, 57, art. no. 100994, .
Yang, P.a , Perlmutter, J.S.a b c d e , Benzinger, T.L.S.a , Morris, J.C.b , Xu, J.a
a Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd, St. Louis, MO 63110, United States
b Department of Neurology, Washington University School of Medicine, 510 S. Kingshighway Blvd, St. Louis, MO 63110, United States
c Department of Neuroscience, Washington University School of Medicine, 510 S. Kingshighway Blvd, St. Louis, MO 63110, United States
d Department of Physical Therapy, Washington University School of Medicine, 510 S. Kingshighway Blvd, St. Louis, MO 63110, United States
e Department of Occupational Therapy, Washington University School of Medicine, 510 S. Kingshighway Blvd, St. Louis, MO 63110, United States
Abstract
Parkinson disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms which relentlessly and progressively lead to substantial disability and economic burden. Pathologically, these symptoms follow the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) associated with abnormal α-synuclein (α-Syn) deposition as cytoplasmic inclusions called Lewy bodies in pigmented brainstem nuclei, and in dystrophic neurons in striatal and cortical regions (Lewy neurites). Pharmacotherapy for PD focuses on improving quality of life and primarily targets dopaminergic pathways. Dopamine acts through two families of receptors, dopamine D1-like and dopamine D2-like; dopamine D3 receptors (D3R) belong to dopamine D2 receptor (D2R) family. Although D3R’s precise role in the pathophysiology and treatment of PD has not been determined, we present evidence suggesting an important role for D3R in the early development and occurrence of PD. Agonist activation of D3R increases dopamine concentration, decreases α-Syn accumulation, enhances secretion of brain derived neurotrophic factors (BDNF), ameliorates neuroinflammation, alleviates oxidative stress, promotes neurogenesis in the nigrostriatal pathway, interacts with D1R to reduce PD associated motor symptoms and ameliorates side effects of levodopa (L-DOPA) treatment. Furthermore, D3R mutations can predict PD age of onset and prognosis of PD treatment. The role of D3R in PD merits further research. This review elucidates the potential role of D3R in PD pathogenesis and therapy. © 2019 The Authors
Author Keywords
BDNF; Dopamine D3 receptor; Neuroinflammation; Parkinson disease; α-Synuclein
Document Type: Review
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Sensory coding mechanisms revealed by optical tagging of physiologically defined neuronal types” (2019) Science (New York, N.Y.)
Sensory coding mechanisms revealed by optical tagging of physiologically defined neuronal types
(2019) Science (New York, N.Y.), 366 (6471), pp. 1384-1389.
Lee, D., Kume, M., Holy, T.E.
Department of Neuroscience, Washington University School of Medicine in St. Louis, St. Louis, MO, USA
Abstract
Neural circuit analysis relies on having molecular markers for specific cell types. However, for a cell type identified only by its circuit function, the process of identifying markers remains laborious. We developed physiological optical tagging sequencing (PhOTseq), a technique for tagging and expression profiling of cells on the basis of their functional properties. PhOTseq was capable of selecting rare cell types and enriching them by nearly 100-fold. We applied PhOTseq to the challenge of mapping receptor-ligand pairings among pheromone-sensing neurons in mice. Together with in vivo ectopic expression of vomeronasal chemoreceptors, PhOTseq identified the complete combinatorial receptor code for a specific set of ligands. Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Gantenerumab reduces amyloid-β plaques in patients with prodromal to moderate Alzheimer’s disease: A PET substudy interim analysis” (2019) Alzheimer’s Research and Therapy
Gantenerumab reduces amyloid-β plaques in patients with prodromal to moderate Alzheimer’s disease: A PET substudy interim analysis
(2019) Alzheimer’s Research and Therapy, 11 (1), art. no. 101, .
Klein, G.a , Delmar, P.b , Voyle, N.c , Rehal, S.c , Hofmann, C.a , Abi-Saab, D.b , Andjelkovic, M.b , Ristic, S.b , Wang, G.d , Bateman, R.d , Kerchner, G.A.b , Baudler, M.b , Fontoura, P.b , Doody, R.b e
a Roche Pharma Research and Early Development, Basel, Switzerland
b Roche/Genentech Product Development, Neuroscience, Basel, Switzerland
c Roche Products Ltd, Welwyn Garden, United Kingdom
d Washington University School of Medicine in St. Louis, St. Louis, MO, United States
e Genentech, Inc., South San Francisco, CA, United States
Abstract
Background: We previously investigated low doses (105 or 225 mg) of gantenerumab, a fully human monoclonal antibody that binds and removes aggregated amyloid-β by Fc receptor-mediated phagocytosis, in the SCarlet RoAD (SR) and Marguerite RoAD (MR) phase 3 trials. Several lines of evidence suggested that higher doses may be necessary to achieve clinical efficacy. We therefore designed a positron emission tomography (PET) substudy to evaluate the effect of gantenerumab uptitrated to 1200 mg every 4 weeks on amyloid-β plaques as measured using florbetapir PET in patients with prodromal to moderate Alzheimer’s disease (AD). Methods: A subset of patients enrolled in the SR and MR studies who subsequently entered the open-label extensions (OLEs) were included in this substudy. Patients were aged 50 to 90 years with a clinical diagnosis of probable prodromal to moderate AD and were included based on a visual read of the original screening scan in the double-blind phase. Patients were assigned to 1 of 5 titration schedules (ranging from 2 to 10 months) with a target gantenerumab dose of 1200 mg every 4 weeks. The main endpoint of this substudy was change in amyloid-β plaque burden from OLE baseline to week 52 and week 104, assessed using florbetapir PET. Florbetapir global cortical signal was calculated using a prespecified standard uptake value ratio method converted to the Centiloid scale. Results: Sixty-seven of the 89 patients initially enrolled had ≥ 1 follow-up scan by August 15, 2018. Mean amyloid levels were reduced by 39 Centiloids by the first year and 59 Centiloids by year 2, a 3.5-times greater reduction than was seen after 2 years at 225 mg in SR. At years 1 and 2, 37% and 51% of patients, respectively, had amyloid-β plaque levels below the amyloid-β positivity threshold. Conclusion: Results from this exploratory interim analysis of the PET substudy suggest that gantenerumab doses up to 1200 mg resulted in robust amyloid-β plaque removal at 2 years. PET amyloid levels were consistent with sparse-to-no neuritic amyloid-β plaques in 51% of patients after 2 years of therapy. Amyloid reductions were similar to those observed in other placebo-controlled studies that have suggested potential clinical benefit. Trial registration: ClinicalTrials.gov, NCT01224106 (SCarlet RoAD) and NCT02051608 (Marguerite RoAD). © 2019 The Author(s).
Author Keywords
Alzheimer’s disease; Amyloid-β plaque; Centiloid; Disease-modification therapies; Florbetapir; Gantenerumab; Open-label extension; Positron emission tomography
Document Type: Article
Publication Stage: Final
Source: Scopus
“Dementia is not synonymous with Alzheimer’s disease” (2019) Science Translational Medicine
Dementia is not synonymous with Alzheimer’s disease
(2019) Science Translational Medicine, 11 (522), art. no. eaav0511, .
Jack, C.a , Holtzman, D.b , Sperling, R.c
a Department of Radiology, Mayo Clinic, Rochester, MN 55905, United States
b Department of Neurology, Washington University, St. Louis, MO 63130, United States
c Department of Neurology, Brigham and Women’s Hospital, Boston, MA 02115, United States
Document Type: Editorial
Publication Stage: Final
Source: Scopus
“NF1 glioblastoma clonal profiling reveals KMT2B mutations as potential somatic oncogenic events” (2019) Neurology
NF1 glioblastoma clonal profiling reveals KMT2B mutations as potential somatic oncogenic events
(2019) Neurology, 93 (24), pp. 1067-1069.
Wong, W.H., Junck, L., Druley, T.E., Gutmann, D.H.
From the Division of Hematology and Oncology (W.H.W., T.E.D.), Department of Pediatrics, Washington University School of Medicine; Edison Family Center for Genome Sciences and Systems Biology (W.H.W., T.E.D.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (L.J.), University of Michigan Health System, Ann Arbor; Department of Neurology (D.H.G.), Washington University School of Medicine, St. Louis, MO
Document Type: Article
Publication Stage: Final
Source: Scopus
“Multicenter, Prospective, Phase II and Biomarker Study of High-Dose Bevacizumab as Induction Therapy in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannoma” (2019) Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Multicenter, Prospective, Phase II and Biomarker Study of High-Dose Bevacizumab as Induction Therapy in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannoma
(2019) Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology, 37 (35), pp. 3446-3454.
Plotkin, S.R.a , Duda, D.G.a , Muzikansky, A.a , Allen, J.b , Blakeley, J.c , Rosser, T.d , Campian, J.L.e , Clapp, D.W.f , Fisher, M.J.g , Tonsgard, J.h , Ullrich, N.i , Thomas, C.j , Cutter, G.j , Korf, B.j , Packer, R.k , Karajannis, M.A.b
a Massachusetts General Hospital, MA, Boston
b New York University, NY, NY
c Johns Hopkins University, MD, Baltimore, United States
d University of Southern California, Los Angeles, CA
e Washington University, St Louis, MO
f Indiana University, IN, Indianapolis, United States
g Children’s Hospital of Philadelphia, Philadelphia, United States
h University of Chicago, Chicago, Mexico
i Boston Children’s Hospital, MA, Boston
j University of Alabama, Birmingham, AL
k Children’s National Medical Center, DCWA
Abstract
PURPOSE: Bevacizumab treatment at 7.5 mg/kg every 3 weeks results in improved hearing in approximately 35%-40% of patients with neurofibromatosis type 2 (NF2) and progressive vestibular schwannomas (VSs). However, the optimal dose is unknown. In this multicenter phase II and biomarker study, we evaluated the efficacy and safety of high-dose bevacizumab in pediatric and adult patients with NF2 with progressive VS. PATIENTS AND METHODS: Bevacizumab was given for 6 months at 10 mg/kg every 2 weeks, followed by 18 months at 5 mg/kg every 3 weeks. The primary end point was hearing response defined by word recognition score (WRS) at 6 months. Secondary end points included toxicity, radiographic response, quality of life (QOL), and plasma biomarkers. RESULTS: Twenty-two participants with NF2 (median age, 23 years) with progressive hearing loss in the target ear (median baseline WRS, 53%) were enrolled. Nine (41%) of 22 participants achieved a hearing response at 6 months (1 of 7 children and 8 of 15 adults; P = .08). Radiographic response was seen in 7 (32%) of 22 patients with VS at 6 months (7 of 15 adults and 0 of 7 children; P = .05). Common mild to moderate adverse events included hypertension, fatigue, headache, and irregular menstruation. Improvement in NF2-related QOL and reduction in tinnitus-related distress were reported in 30% and 60% of participants, respectively. Paradoxically, high-dose bevacizumab treatment was not associated with a significant decrease in free vascular endothelial growth factor but was associated with increased carbonic anhydrase IX, hepatocyte growth factor, placental growth factor, stromal cell-derived factor 1α, and basic fibroblast growth factor concentrations in plasma. CONCLUSION: High-dose bevacizumab seems to be no more effective than standard-dose bevacizumab for treatment of patients with NF2 with hearing loss. In contrast to adults, pediatric participants did not experience tumor shrinkage. However, adult and pediatric participants reported similar improvement in QOL during induction. Novel approaches using bevacizumab should be considered for children with NF2.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Confronting the Opioid Crisis: Practical Pain Management and Strategies: AOA 2018 Critical Issues Symposium” (2019) The Journal of Bone and Joint Surgery. American volume
Confronting the Opioid Crisis: Practical Pain Management and Strategies: AOA 2018 Critical Issues Symposium
(2019) The Journal of Bone and Joint Surgery. American volume, 101 (23), p. e126.
Mir, H.R.a , Miller, A.N.b , Obremskey, W.T.c , Jahangir, A.A.c , Hsu, J.R.d
a Department of Orthopaedic Surgery, University of South Florida, Florida Orthopedic Institute, Tampa, FL, Romania
b Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, United States
c Department of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, TN, United States
d Atrium Health Musculoskeletal Institute, Carolinas Medical Center, Charlotte, North Carolina
Abstract
The United States is in the midst of an opioid crisis. Clinicians have been part of the problem because of overprescribing of narcotics for perioperative pain management. Clinicians need to understand the pathophysiology and science of addiction to improve perioperative management of pain for their patients. Multiple modalities for pain management exist that decrease the use of narcotics. Physical strategies, cognitive strategies, and multimodal medication can all provide improved pain relief and decrease the use of narcotics. National medical societies are developing clinical practice guidelines for pain management that incorporate multimodal strategies and multimodal medication. Changes to policy that improve provider education, access to naloxone, and treatment for addiction can decrease narcotic misuse and the risk of addiction.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Association of Longitudinal Changes in Cerebrospinal Fluid Total Tau and Phosphorylated Tau 181 and Brain Atrophy With Disease Progression in Patients With Alzheimer Disease” (2019) JAMA Network Open
Association of Longitudinal Changes in Cerebrospinal Fluid Total Tau and Phosphorylated Tau 181 and Brain Atrophy With Disease Progression in Patients With Alzheimer Disease
(2019) JAMA Network Open, 2 (12), p. e1917126.
Llibre-Guerra, J.J.a , Li, Y.b , Schindler, S.E.a , Gordon, B.A.c , Fagan, A.M.a d , Morris, J.C.a e f , Benzinger, T.L.S.c , Hassenstab, J.a , Wang, G.g , Allegri, R.h , Berman, S.B.c i , Chhatwal, J.j , Farlow, M.R.k , Holtzman, D.M.a e f , Jucker, M.g l , Levin, J.m n o , Noble, J.M.p , Salloway, S.q , Schofield, P.r s , Karch, C.t , Fox, N.C.u , Xiong, C.b , Bateman, R.J.a , McDade, E.a
a Department of Neurology, Washington University in St Louis, St Louis, MO, United States
b Department of Biostatistics, Washington University in St Louis, St Louis, MO, United States
c Department of Radiology, Washington University in St Louis, St Louis, MO, United States
d Department of Pathology and Immunology, Washington University School of Medicine in St Louis, St Louis, MO, United States
e Hope Center for Neurological Disorders, St Louis, MO, United States
f Knight Alzheimer’s Disease Research Center, St Louis, MO, United States
g Hertie Institute for Clinical Brain Research, Department of Cellular Neurology, University of Tübingen, Tübingen, Germany
h Department of Cognitive Neurology, Institute for Neurological Research FleniBuenos Aires, Argentina
i Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States
j Massachusetts General Hospital, Harvard Medical School, Boston
k Neuroscience Center, Indiana University, Bloomington, United States
l DZNE-German Center for Neurodegenerative Diseases, Tübingen, Germany
m Department of Neurology, Ludwig-Maximilians-University, Munich, Germany
n DZNE-German Center for Neurodegenerative Diseases, Munich, Germany
o SyNergy, Munich Cluster for Systems Neurology, Munich, Germany
p Taub Institute for Research on Alzheimer’s Disease, Aging Brain G.H. Sergievsky Center, Department of Neurology, Columbia University Medical CenterNY
q Memory & Aging Program, Butler Hospital, Brown University, Providence, RI, United States
r Neuroscience Research Australia, Randwick, Sydney, New South Wales, Australia
s School of Medical Sciences, UNSW Sydney, Sydney, NSW, Australia
t Department of Psychiatry, Washington University in St Louis, St Louis, MO, United States
u Dementia Research Centre, University College London, London, United Kingdom
Abstract
Importance: The amyloid/tau/neurodegeneration (A/T/N) framework uses cerebrospinal fluid (CSF) levels of total tau (tTau) as a marker of neurodegeneration and CSF levels of phosphorylated tau 181 (pTau181) as a marker of tau tangles. However, it is unclear whether CSF levels of tTau and pTau181 have similar or different trajectories over the course of Alzheimer disease. Objectives: To examine the rates of change in CSF levels of tTau and pTau181 across the Alzheimer disease course and how the rates of change are associated with brain atrophy as measured by magnetic resonance imaging. Design, Setting, and Participants: This cohort study was set in tertiary research clinics. Each participant was a member of a pedigree with a known mutation for dominantly inherited Alzheimer disease. Participants were divided into 3 groups on the basis of the presence of a mutation and their Clinical Dementia Rating score. Data analysis was performed in June 2019. Main Outcomes and Measures: Rates of change of CSF tTau and pTau181 levels and their association with the rate of change of brain volume. Results: Data from 465 participants (283 mutation carriers and 182 noncarriers) were analyzed. The mean (SD) age of the cohort was 37.8 (11.3) years, and 262 (56.3%) were women. The mean (SD) follow-up duration was 2.7 (1.5) years. Two or more longitudinal CSF and magnetic resonance imaging assessments were available for 160 and 247 participants, respectively. Sixty-five percent of mutation carriers (183) did not have symptoms at baseline (Clinical Dementia Rating score, 0). For mutation carriers, the annual rates of change for CSF tTau and pTau181 became significantly different from 0 approximately 10 years before the estimated year of onset (mean [SE] rates of change, 5.5 [2.8] for tTau [P = .05] and 0.7 [0.3] for pTau 181 [P = .04]) and 15 years before onset (mean [SE] rates of change, 5.4 [3.9] for tTau [P = .17] and 1.1 [0.5] for pTau181 [P = .03]), respectively. The rate of change of pTau181 was positive and increased at the early stages of the disease, showing a positive rate of change starting at 15 estimated years before onset until 5 estimated years before onset (mean [SE], 0.4 [0.3]), followed by a positive but decreasing rate of change at year 0 (mean [SE], 0.1 [0.3]) and then negative rates of change at 5 years (mean [SE], -0.3 [0.4]) and 10 years (mean [SE], -0.6 [0.6]) after symptom onset. In individuals without symptoms (Clinical Dementia Rating score, 0), the rates of change of CSF tTau and pTau181 were negatively associated with brain atrophy (high rates of change in CSF measures were associated with low rates of change in brain volume in asymptomatic stages). After symptom onset (Clinical Dementia Rating score, >0), an increased rate of brain atrophy was not associated with rates of change of levels of both CSF tTau and pTau181. Conclusions and Relevance: These findings suggest that CSF tTau and pTau181 may have different associations with brain atrophy across the disease time course. These results have implications for understanding the dynamics of disease pathobiology and interpreting neuronal injury biomarker concentrations in response to Alzheimer disease progression and disease-modifying therapies.
Document Type: Article
Publication Stage: Final
Source: Scopus
“22q11.2 duplication: a review of neuropsychiatric correlates and a newly observed case of prototypic sociopathy” (2019) Cold Spring Harbor Molecular Case Studies
22q11.2 duplication: a review of neuropsychiatric correlates and a newly observed case of prototypic sociopathy
(2019) Cold Spring Harbor Molecular Case Studies, 5 (6), .
Vyas, S.a , Constantino, J.N.b , Baldridge, D.c
a St. Louis University School of Medicine, St. Louis, MO 63104, United States
b Division of Child Psychiatry, Department of Psychiatry, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, United States
c Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Callous-unemotional (CU) traits are highly disabling behavioral characteristics, common predictors of delinquency and criminality, and pathognomonic for antisocial personality disorder. They are highly heritable, but their specific molecular genetic causes are unknown. Here, we briefly review the literature on neuropsychiatric correlates of 22q11.2 duplication and describe a newly identified case of a 737-kb microduplication within the low copy repeat (LCR) B-D region, involving a 13-yr-old early adoptee with mild developmental delay and severe, chronic antisocial behavior of early childhood onset. When psychiatric symptoms have been reported in relation to duplications in this specific region, 19% of the reports feature aggression-but never previously CU traits-as a component of the phenotype. We discuss the potential implications of gain of function in this chromosomal region for heritable origins of sociopathy and their possible relation to genetic influences on aggression. © 2019 Vyas et al.; Published by Cold Spring Harbor Laboratory Press.
Author Keywords
aggressive behavior; attention deficit hyperactivity disorder; oppositional defiant disorder
Document Type: Article
Publication Stage: Final
Source: Scopus
“TRPV1 activity and substance P release are required for corneal cold nociception” (2019) Nature Communications
TRPV1 activity and substance P release are required for corneal cold nociception
(2019) Nature Communications, 10 (1), art. no. 5678, .
Li, F.a b , Yang, W.a , Jiang, H.a , Guo, C.a , Huang, A.J.W.c , Hu, H.a , Liu, Q.a c
a Department of Anesthesiology, Center for the Study of Itch and Sensory Disorders, Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, United States
b Department of Anesthesiology, Zhujiang Hospital of Southern Medical University, Guangdong, China
c Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States
Abstract
As a protective mechanism, the cornea is sensitive to noxious stimuli. Here, we show that in mice, a high proportion of corneal TRPM8+ cold-sensing fibers express the heat-sensitive TRPV1 channel. Despite its insensitivity to cold, TRPV1 enhances membrane potential changes and electrical firing of TRPM8+ neurons in response to cold stimulation. This elevated neuronal excitability leads to augmented ocular cold nociception in mice. In a model of dry eye disease, the expression of TRPV1 in TRPM8+ cold-sensing fibers is increased, and results in severe cold allodynia. Overexpression of TRPV1 in TRPM8+ sensory neurons leads to cold allodynia in both corneal and non-corneal tissues without affecting their thermal sensitivity. TRPV1-dependent neuronal sensitization facilitates the release of the neuropeptide substance P from TRPM8+ cold-sensing neurons to signal nociception in response to cold. Our study identifies a mechanism underlying corneal cold nociception and suggests a potential target for the treatment of ocular pain. © 2019, The Author(s).
Document Type: Article
Publication Stage: Final
Source: Scopus
“Executive task-based brain function in children with type 1 diabetes: An observational study” (2019) PLoS Medicine
Executive task-based brain function in children with type 1 diabetes: An observational study
(2019) PLoS Medicine, 16 (12), p. e1002979.
Foland-Ross, L.C.a , Buckingam, B.b , Mauras, N.c , Arbelaez, A.M.d , Tamborlane, W.V.e , Tsalikian, E.f , Cato, A.g , Tong, G.a , Englert, K.c , Mazaika, P.K.a , Reiss, A.L.a h i , Diabetes Research in Children Network (DirecNet)j
a Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States
b Division of Pediatric Endocrinology and Diabetes, Stanford University School of Medicine, Stanford, CA, United States
c Division of Endocrinology, Diabetes and Metabolism, Nemours Children’s Health System, Jacksonville, FL, United States
d Division of Endocrinology, Washington University, Saint Louis, Missouri, United States of America
e Division of Endocrinology, Yale University, New Haven, CT, United States
f Division of Endocrinology, University of Iowa, Iowa City, IA, United States
g Division of Neurology, Nemours Children’s Health System, Jacksonville, FL, United States
h Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, United States
i Department of Radiology, Stanford University School of Medicine, Stanford, CA, United States
Abstract
BACKGROUND: Optimal glycemic control is particularly difficult to achieve in children and adolescents with type 1 diabetes (T1D), yet the influence of dysglycemia on the developing brain remains poorly understood. METHODS AND FINDINGS: Using a large multi-site study framework, we investigated activation patterns using functional magnetic resonance imaging (fMRI) in 93 children with T1D (mean age 11.5 ± 1.8 years; 45.2% female) and 57 non-diabetic (control) children (mean age 11.8 ± 1.5 years; 50.9% female) as they performed an executive function paradigm, the go/no-go task. Children underwent scanning and cognitive and clinical assessment at 1 of 5 different sites. Group differences in activation occurring during the contrast of “no-go > go” were examined while controlling for age, sex, and scan site. Results indicated that, despite equivalent task performance between the 2 groups, children with T1D exhibited increased activation in executive control regions (e.g., dorsolateral prefrontal and supramarginal gyri; p = 0.010) and reduced suppression of activation in the posterior node of the default mode network (DMN; p = 0.006). Secondary analyses indicated associations between activation patterns and behavior and clinical disease course. Greater hyperactivation in executive control regions in the T1D group was correlated with improved task performance (as indexed by shorter response times to correct “go” trials; r = -0.36, 95% CI -0.53 to -0.16, p < 0.001) and with better parent-reported measures of executive functioning (r values < -0.29, 95% CIs -0.47 to -0.08, p-values < 0.007). Increased deficits in deactivation of the posterior DMN in the T1D group were correlated with an earlier age of T1D onset (r = -0.22, 95% CI -0.41 to -0.02, p = 0.033). Finally, exploratory analyses indicated that among children with T1D (but not control children), more severe impairments in deactivation of the DMN were associated with greater increases in hyperactivation of executive control regions (T1D: r = 0.284, 95% CI 0.08 to 0.46, p = 0.006; control: r = 0.108, 95% CI -0.16 to 0.36, p = 0.423). A limitation to this study involves glycemic effects on brain function; because blood glucose was not clamped prior to or during scanning, future studies are needed to assess the influence of acute versus chronic dysglycemia on our reported findings. In addition, the mechanisms underlying T1D-associated alterations in activation are unknown. CONCLUSIONS: These data indicate that increased recruitment of executive control areas in pediatric T1D may act to offset diabetes-related impairments in the DMN, ultimately facilitating cognitive and behavioral performance levels that are equivalent to that of non-diabetic controls. Future studies that examine whether these patterns change as a function of improved glycemic control are warranted.
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Upfront Magnetic Resonance Imaging-Guided Stereotactic Laser-Ablation in Newly Diagnosed Glioblastoma: A Multicenter Review of Survival Outcomes Compared to a Matched Cohort of Biopsy-Only Patients” (2019) Clinical Neurosurgery
Upfront Magnetic Resonance Imaging-Guided Stereotactic Laser-Ablation in Newly Diagnosed Glioblastoma: A Multicenter Review of Survival Outcomes Compared to a Matched Cohort of Biopsy-Only Patients
(2019) Clinical Neurosurgery, 85 (6), pp. 762-772.
Mohammadi, A.M.a , Sharma, M.a , Beaumont, T.L.b , Juarez, K.O.c , Kemeny, H.d , Dechant, C.d , Seas, A.d , Sarmey, N.a , Lee, B.S.a , Jia, X.e , Fecci, P.E.d , Baehring, J.c , Moliterno, J.c , Chiang, V.L.c , Ahluwalia, M.S.a , Kim, A.H.b , Barnett, G.H.a , Leuthardt, E.C.b f g
a Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Department of Neurosurgery, Neurological Institute, Cleveland Clinic, Lerner College of Medicine, 9500 Euclid Ave. CA-51, Cleveland, OH 44195, United States
b Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, United States
c Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, United States
d Department of Neurosurgery, Duke University Medical Center, Durham, NC, United States
e Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, United States
f Department of Biomedical Engineering, Center for Innovation in Neuroscience and Technology, Washington University School of Medicine, St. Louis, MO, United States
g Department of Mechanical Engineering and Material Science, Center for Innovation in Neuroscience and Technology, Washington University, School of Medicine, St. Louis, MO, United States
Abstract
BACKGROUND: Laser ablation (LA) is used as an upfront treatment in patients with deep seated newly diagnosed Glioblastoma (nGBM). OBJECTIVE: To evaluate the outcomes of LA in patients with nGBM and compare them with a matched biopsy-only cohort. METHODS: Twenty-four nGBM patients underwent upfront LA at Cleveland clinic, Washington University in St. Louis, and Yale University (6/2011-12/2014) followed by chemo/radiotherapy. Also, 24 out of 171 nGBM patients with biopsy followed by chemo/radiotherapy were matched based on age (< 70 vs ≥ 70), gender, tumor location (deep vs lobar), and volume (<11 cc vs ≥11 cc). Progression-free survival (PFS), overall survival (OS), and disease-specific PFS and OS were outcome measures. Three prognostic groups were identified based on extent of tumor ablation by thermal-damage-threshold (TDT)-lines. RESULTS: The median tumor volume in LA (n = 24) and biopsy only (n = 24) groups was 9.3 cm3 and 8.2 cm3 respectively. Overall, median estimate of OS and PFS in LA cohort was 14.4 and 4.3 mo compared to 15.8 mo and 5.9 mo for biopsy only cohort. On multivariate analysis, favorable TDT-line prognostic groups were associated with lower incidence of disease specific death (P =. 03) and progression (P =. 05) compared to other groups including biopsy only cohort. Only age (<70 yr, P =. 02) and tumor volume (<11 cc, P =. 03) were favorable prognostic factors for OS. CONCLUSION: The maximum tumor coverage by LA followed by radiation/chemotherapy is an effective treatment modality in patients with nGBM, compared to biopsy only cohort. The TDT-line prognostic groups were independent predictor of disease specific death and progression after LA. © 2018 by the Congress of Neurological Surgeons.
Author Keywords
Brain tumor; GBM; LITT; Minimally invasive; NeuroBlate; Novel treatment
Document Type: Review
Publication Stage: Final
Source: Scopus
“Cantú syndrome: Findings from 74 patients in the International Cantú Syndrome Registry” (2019) American Journal of Medical Genetics, Part C: Seminars in Medical Genetic
Cantú syndrome: Findings from 74 patients in the International Cantú Syndrome Registry
(2019) American Journal of Medical Genetics, Part C: Seminars in Medical Genetics, 181 (4), pp. 658-681. Cited 1 time.
Grange, D.K.a b , Roessler, H.I.c , McClenaghan, C.b d , Duran, K.c , Shields, K.a , Remedi, M.S.b e , Knoers, N.V.A.M.f g , Lee, J.-M.h , Kirk, E.P.i j , Scurr, I.k , Smithson, S.F.k , Singh, G.K.a b , van Haelst, M.M.l m , Nichols, C.G.b d , van Haaften, G.c
a Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
b Center for the Investigation of Membrane Excitability Diseases (CIMED), United States
c Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
d Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO, United States
e Department of Medicine, Division of Endocrinology, Washington University School of Medicine, St. Louis, MO, United States
f Department of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
g Department of Genetics, University Medical Center Groningen, Groningen, Netherlands
h Department of Neurology and Radiology, Washington University School of Medicine, St. Louis, MO, United States
i Centre for Clinical Genetics, Sydney Children’s Hospital, Randwick, NSW, Australia
j School of Women’s and Children’s Health, University of New South Wales, Randwick, NSW, Australia
k Department of Clinical Genetics, University Hospitals, Bristol, United Kingdom
l Department of Clinical Genetics, VU Medical Center, VU University Amsterdam, Amsterdam, Netherlands
m Department of Clinical Genetics, Amsterdam Medical Center, University of Amsterdam, Amsterdam, Netherlands
Abstract
Cantú syndrome (CS), first described in 1982, is caused by pathogenic variants in ABCC9 and KCNJ8, which encode the regulatory and pore forming subunits of ATP-sensitive potassium (KATP) channels, respectively. Multiple case reports of affected individuals have described the various clinical features of CS, but systematic studies are lacking. To define the effects of genetic variants on CS phenotypes and clinical outcomes, we have developed a standardized REDCap-based registry for CS. We report phenotypic features and associated genotypes on 74 CS subjects, with confirmed ABCC9 variants in 72 of the individuals. Hypertrichosis and a characteristic facial appearance are present in all individuals. Polyhydramnios during fetal life, hyperflexibility, edema, patent ductus arteriosus (PDA), cardiomegaly, dilated aortic root, vascular tortuosity of cerebral arteries, and migraine headaches are common features, although even with this large group of subjects, there is incomplete penetrance of CS-associated features, without clear correlation to genotype. © 2019 Wiley Periodicals, Inc.
Author Keywords
ABCC9; Cantú; cardiomegaly; hypertrichosis; PDA; polyhydramnios
Document Type: Article
Publication Stage: Final
Source: Scopus
“Surgery and persistent cognitive decline: a commentary and an independent discussion” (2019) British Journal of Anaesthesia
Surgery and persistent cognitive decline: a commentary and an independent discussion
(2019) British Journal of Anaesthesia, .
Whitlock, E.L.a , Grisell Diaz-Ramirez, L.b , Avidan, M.S.c
a Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, CA, United States
b Division of Geriatrics, Department of Medicine, University of California San Francisco, San Francisco, CA, United States
c Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
Document Type: Editorial
Publication Stage: Article in Press
Source: Scopus
“Outcome of patients with large vessel occlusion stroke after first admission in telestroke spoke versus comprehensive stroke center” (2019) Journal of NeuroInterventional Surgery
Outcome of patients with large vessel occlusion stroke after first admission in telestroke spoke versus comprehensive stroke center
(2019) Journal of NeuroInterventional Surgery, art. no. 015342, .
Kaminsky, A.-L.a , Mione, G.a , Omorou, Y.b , Humbertjean, L.a , Bonnerot, M.a , Lacour, J.C.a , Riou-Comte, N.a , Anadani, M.c d , Gory, B.e , Richard, S.a f
a Department of Neurology, Stroke Unit, University Hospital of Nancy, Nancy, France
b Centre d’Investigation Clinique-CIC 1433 Epidémiologie Clinique, CHU Nancy, Lorraine Nancy, France
c Washington University School of Medicine in St Louis, St Louis, MO, United States
d Neurology, Medical University of South Carolina-College of Medicine, Charleston, SC, United States
e Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Nancy INSERM U1254, Nancy, France
f Centre d’Investigation Clinique Plurithématique CIC 1433, CHRU, Lorraine Nancy, France
Abstract
Introduction: While telestroke allows early intravenous thrombolysis (IVT) for ischemic strokes in spoke centers, mechanical thrombectomy (MT) for large vessel occlusion (LVO) is mainly performed at comprehensive stroke centers (CSCs). We aimed to compare 3 month outcome in patients with LVO after admission to a spoke center using telestroke compared with first CSC admission in our large regional stroke network, irrespective of final treatment decision. Methods: All consecutive LVO patients who were admitted to one of six spoke centers or to the regional CSC within 6 hours of symptom onset were prospectively included from September 1, 2015 to August 31, 2017. All patients admitted to spoke centers were assessed on site with cerebral and vessel imaging. Primary outcome was 3 month favorable outcome (modified Rankin Scale score of 0-2). Results: Distances between spoke centers and CSC ranged from 36 to 77 miles. Among 207 included patients, 132 (63.8%) were first admitted to CSCs and 75 (36.2%) to spoke centers. IVT was administered more in spoke centers (81.3% vs 53.8%, p<0.0001) while MT was performed less (26.7% vs 49.2%, p=0.001) and with a longer time from onset (303 vs 200 min, p<0.0001). No difference was found in 3 month favorable outcome between spoke centers compared with CSCs (32.0% and 35.1%, respectively; OR=0.68; 95% CI 0.42 to 1.10; p=0.12). Conclusions: Despite different distribution of reperfusion therapies for LVO patients managed by telemedicine, we could not demonstrate a difference in functional outcome according to admission location in a large area with long distances between centers. © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
Author Keywords
stroke; thrombectomy; thrombolysis
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“The Relation between Personality and Biomarkers in Sensitivity and Conversion to Alzheimer-Type Dementia” (2019) Journal of the International Neuropsychological Society
The Relation between Personality and Biomarkers in Sensitivity and Conversion to Alzheimer-Type Dementia
(2019) Journal of the International Neuropsychological Society, .
Duchek, J.M.a , Aschenbrenner, A.J.b c , Fagan, A.M.b c , Benzinger, T.L.S.c d e , Morris, J.C.b c , Balota, D.A.a
a Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO 63130, United States
b Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110, United States
c Knight Alzheimer’s Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, United States
d Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, United States
e Department of Neurological Surgery, Washington University in St. Louis, St. Louis, MO 63110, United States
Abstract
Objectives:The present study explored relationships among personality, Alzheimer’s disease (AD) biomarkers, and dementia by addressing the following questions: (1) Does personality discriminate healthy aging and earliest detectable stage of AD? (2) Does personality predict conversion from healthy aging to early-stage AD? (3) Do AD biomarkers mediate any observed relationships between personality and dementia status/conversion?Methods:Both self- and informant ratings of personality were obtained in a large well-characterized longitudinal sample of cognitively normal older adults (N = 436) and individuals with early-stage dementia (N = 74). Biomarkers included amyloid imaging, hippocampal volume, cerebral spinal fluid (CSF) Aβ42, and CSF tau.Results:Higher neuroticism, lower conscientiousness, along with all four biomarkers strongly discriminated cognitively normal controls from early-stage AD individuals. The direct effects of neuroticism and conscientiousness were only mediated by hippocampal volume. Conscientiousness along with all biomarkers predicted conversion from healthy aging to early-stage AD; however, none of the biomarkers mediated the relationship between conscientiousness and conversion. Conscientiousness predicted conversion as strongly as the biomarkers, with the exception of hippocampal volume.Conclusions:Conscientiousness and to a lesser extent neuroticism serve as important independent behavioral markers for AD risk. © INS. Published by Cambridge University Press, 2019.
Author Keywords
Aging; Alzheimer’s disease; Biomarkers; Dementia; Older adults; Personality
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Cannabis vaping and health: regulatory considerations” (2019) Addiction
Cannabis vaping and health: regulatory considerations
(2019) Addiction, .
Borodovsky, J.T., Cavazos-Rehg, P.A., Bierut, L.J., Grucza, R.A.
Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, United States
Author Keywords
Cannabis; concentrates; public health; regulation; respiratory; vaping
Document Type: Letter
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access
“Sorting nexin 27 (SNX27) variants associated with seizures, developmental delay, behavioral disturbance, and subcortical brain abnormalities” (2019) Clinical Genetics
Sorting nexin 27 (SNX27) variants associated with seizures, developmental delay, behavioral disturbance, and subcortical brain abnormalities
(2019) Clinical Genetics, .
Parente, D.J.a , Morris, S.M.b , McKinstry, R.C.c , Brandt, T.d , Gabau, E.e , Ruiz, A.f , Shinawi, M.g
a Department of Family Medicine, University of Kansas Medical Center, Kansas City, KS, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
c Pediatric Radiology and Pediatric Neuroradiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, United States
d GeneDx, Gaithersburg, MD, United States
e Paediatric Unit, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain
f Genetics Laboratory, UDIAT-Centre Diagnòstic, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, Sabadell, Spain
g Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Sorting nexin 27 (SNX27) influences the composition of the cellular membrane via regulation of selective endosomal recycling. Molecular analysis indicates that SNX27 regulates numerous cellular processes through promiscuous interactions with its receptor cargos. SNX27 deficient (Snx27−/−) mice exhibit reduced embryonic survival, marked postnatal growth restriction and lethality. Haploinsufficient mice (Snx27+/−) show a less severe phenotype, with deficits in learning, memory, synaptic transmission and neuronal plasticity. One family previously reported with a homozygous SNX27 frameshift variant (c.515_516del;p.His172Argfs*6), exhibited infantile intractable myoclonic epilepsy, axial hypotonia, startle-like movements, cardiac septal defects, global developmental delay, failure to thrive, recurrent chest infections, persistent hypoxemia and early death secondary to respiratory failure. Here, we report two additional patients with compound heterozygous SNX27 variants, that are predicted to be damaging: (a) c.510C>G;p.Tyr170* and c.1295G>A;p.Cys432Tyr, and (b) c.782dupT;p.Leu262Profs*6 and c.989G>A;p.Arg330His. They exhibit global developmental delay, behavioral disturbance, epilepsy, some dysmorphic features and subcortical white matter abnormalities. In addition, possible connective tissue involvement was noted. Epilepsy, developmental delays and subcortical white matter abnormalities appear to be core features of SNX27-related disorders. We correlate the observed phenotype with available in vitro, in vivo and proteomic data and suggest additional possible molecular mediators of SNX27-related pathology. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Author Keywords
behavioral disturbance; developmental delay; endosome; epilepsy; exome sequencing; retromer; seizures; SNX27; sorting nexin
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“What Is the Role of Ketamine in Postoperative Pain Management?” (2019) Journal of Cardiothoracic and Vascular Anesthesia
What Is the Role of Ketamine in Postoperative Pain Management?
(2019) Journal of Cardiothoracic and Vascular Anesthesia, .
Maranhao, B., Gregory, S.H.
Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, United States
Document Type: Editorial
Publication Stage: Article in Press
Source: Scopus
“Disease-Modifying Therapy Adherence and Associated Factors in a National Sample of Medicare Patients With Multiple Sclerosis” (2019) Value in Health
Disease-Modifying Therapy Adherence and Associated Factors in a National Sample of Medicare Patients With Multiple Sclerosis
(2019) Value in Health, .
Li, P.a , Ladage, V.P.a , Berger, J.a , Chahin, S.b , Jhaveri, M.c , Geremakis, C.d , Doshi, J.A.a
a Division of General Internal Medicine, University of Pennsylvania, Philadelphia, PA, United States
b Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
c Global Value and Access, Biogen, Cambridge, MA, United States
d Medical Value Strategy and Execution, Biogen, WestonMA, United States
Abstract
Objectives: Disease-modifying therapies (DMTs) reduce relapse rates and disability progression for relapsing multiple sclerosis (MS). Although 25% to 30% of all US patients with MS are Medicare beneficiaries, limited information exists on this population. This is the first study using national Medicare data to (1) describe characteristics of patients with MS using DMTs, (2) estimate adherence to DMTs over a 1-year and 3-year follow-up, and (3) examine factors associated with DMT adherence. Methods: This retrospective claims analysis used 2011-2014 100% Medicare files. Monthly adherence to MS DMTs was defined as the proportion of days covered ≥0.80 with any DMT in each month for 1-year (n = 36 593) and 3-year (n = 17 599) follow-up samples of MS DMT users. Generalized estimating equation logistic regressions were used to estimate factors associated with adherence to DMTs. Results: Over 90% of patients were eligible for Medicare owing to disability, and about three-quarters qualified for low-income subsidies. A downward trend in DMT adherence was observed over time in both samples. Monthly adherence dropped significantly between December of the prior year to January of the following year (from 76% to 65% in the 1-year follow-up sample and similar drops seen across all years in the 3-year follow-up sample). Multivariable regressions indicated characteristics such as being low-income, having a disability, and having high patient out-of-pocket DMT costs associated with poor adherence to DMTs. Conclusion: Our study provides important insights into the characteristics and DMT adherence of Medicare patients with MS and highlights the need for interventions and policies mitigating barriers to adherence in this population. © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research
Author Keywords
adherence; administrative claims data; disease-modifying therapies; Medicare; multiple sclerosis
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access
“Screening for cognitive impairment in older adults with hematological malignancies using the Montreal Cognitive Assessment and neuropsychological testing” (2019) Journal of Geriatric Oncology
Screening for cognitive impairment in older adults with hematological malignancies using the Montreal Cognitive Assessment and neuropsychological testing
(2019) Journal of Geriatric Oncology, .
Koll, T.T.a , Sheese, A.N.b , Semin, J.a , Ernst, W.a , High, R.c , Wildes, T.M.d , Fisher, A.a , Murman, D.L.e
a Division of Geriatrics, Gerontology, and Palliative Medicine, Department of Internal Medicine, University of Nebraska Medical Center, 986155 Nebraska Medical Center, Omaha, NE 68198-6155, United States
b Division of Neuropsychology, Department of Neurological Sciences, 988425 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE 68198-8425, United States
c Department of Biostatistics, University of Nebraska Medical Center, 984375 Nebraska Medical Center, Omaha, NE 68198-4375, United States
d Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, 660 South Euclid Ave., Campus Box 8056, St. Louis, MO 63110, United States
e Department of Neurological Sciences, University of Nebraska Medical Center, 988440 Nebraska Medical Center, Omaha, NE 68198-8440, United States
Abstract
Objectives: The primary objective of the current study is to describe the prevalence and profile of cognitive domains affected in older adults with hematological malignancies evaluated for hematopoietic cell transplantation (HCT) using the Montreal Cognitive Assessment (MoCA) and neuropsychological tests. The secondary objective is to determine if a specific MoCA cut-off score would correlate with the identification of cognitive impairment detected by neuropsychological tests. This would facilitate interpretation of cognitive screening and referral of patients who would likely need further neuropsychological testing. Materials and Methods: Fifty-one patients 60 years and older who were evaluated for HCT were assessed using a battery of standardized neuropsychological tests and MoCA. We analyzed Receiver Operating Characteristics (ROC) comparing MoCA scores and four different neuropsychological test criteria for cognitive impairment. Results: The prevalence of cognitive impairment detected by neuropsychological tests was 53 to 70.6% using the criteria for patients with cancer by the International Cancer Cognition Task Force (ICCTF). The following cognitive domains were most affected: language, learning and memory, visuospatial skills, and executive function. MoCA is an appropriate screening test for cognitive impairment. Using the ICCTF criteria, 86 to 100% of patients are correctly classified as having significant cognitive impairment on neuropsychological tests using a cut-off score of 20 or less. Conclusion: There is a high prevalence of cognitive impairment identified by neuropsychological tests in older patients with hematological malignancies evaluated for HCT. Identification of an appropriate MoCA cut-off score in this population is important to identify patients who would benefit from further assessment. © 2019 Elsevier Inc.
Author Keywords
Cognitive impairment; Cognitive screens; Hematological malignancies; Hematopoietic cell transplant; Montreal Cognitive Assessment (MoCA); Neuropsychological tests; Older adults
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Vasopressor drugs for the prevention and treatment of hypotension during neuraxial anaesthesia for Caesarean delivery: a Bayesian network meta-analysis of fetal and maternal outcomes” (2019) British Journal of Anaesthesia
Vasopressor drugs for the prevention and treatment of hypotension during neuraxial anaesthesia for Caesarean delivery: a Bayesian network meta-analysis of fetal and maternal outcomes
(2019) British Journal of Anaesthesia, .
Singh, P.M.a , Singh, N.P.b , Reschke, M.c , Kee, W.D.N.d , Palanisamy, A.a , Monks, D.T.a
a Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, United States
b Department of Anesthesiology, MM Super Specialty Hospital, Mullana, Ambala, Haryana, India
c Department of Anesthesia, Johns Hopkins University, Baltimore, MD, United States
d Department of Anesthesiology, Sidra Medicine, Doha, Qatar
Abstract
Background: The optimal choice of vasopressor drugs for managing hypotension during neuraxial anaesthesia for Caesarean delivery is unclear. Although phenylephrine was recently recommended as a consensus choice, direct comparison of phenylephrine with vasopressors used in other healthcare settings is largely lacking. Therefore, we assessed this indirectly by collating data from relevant studies in this comprehensive network meta-analysis. Here, we provide the possible rank orders for these vasopressor agents in relation to clinically important fetal and maternal outcomes. Methods: RCTs were independently searched in MEDLINE, Web of Science, Embase, The Cochrane Central Register of Controlled Trials, and clinicaltrials.gov (updated January 31, 2019). The primary outcome assessed was umbilical arterial base excess. Secondary fetal outcomes were umbilical arterial pH and PCO2. Maternal outcomes were incidences of nausea, vomiting, and bradycardia. Results: We included 52 RCTs with a total of 4126 patients. Our Bayesian network meta-analysis showed the likelihood that norepinephrine, metaraminol, and mephentermine had the lowest probability of adversely affecting the fetal acid-base status as assessed by their effect on umbilical arterial base excess (probability rank order: norepinephrine > mephentermine > metaraminol > phenylephrine > ephedrine). This rank order largely held true for umbilical arterial pH and PCO2. With the exception of maternal bradycardia, ephedrine had the highest probability of being the worst agent for all assessed outcomes. Because of the inherent imprecision when collating direct/indirect comparisons, the rank orders suggested are possibilities rather than absolute ranks. Conclusion: Our analysis suggests the possibility that norepinephrine and metaraminol are less likely than phenylephrine to be associated with adverse fetal acid-base status during Caesarean delivery. Our results, therefore, lay the scientific foundation for focused trials to enable direct comparisons between these agents and phenylephrine. © 2019 British Journal of Anaesthesia
Author Keywords
Caesarean section, fetal outcomes; maternal outcomes, hypotension; network meta-analysis, vasopressors; spinal anaesthesia
Document Type: Review
Publication Stage: Article in Press
Source: Scopus
“Erratum: Correction to: Qualitative vs. Quantitative Methods in Psychiatric Research: Updated (Methods in molecular biology (Clifton, N.J.))” (2019) Methods in Molecular Biology (Clifton, N.J.)
Erratum: Correction to: Qualitative vs. Quantitative Methods in Psychiatric Research: Updated (Methods in molecular biology (Clifton, N.J.))
(2019) Methods in Molecular Biology (Clifton, N.J.), 2011, p. C1.
Srivastava, A.B.a , Kobeissy, F.H.b , Gold, M.S.c
a Division on Substance Use Disorder, Department of Psychiatry, Columbia University Medical Center, New York State Psychiatric Institute, NY, NY, United States
b Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
c Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
Abstract
Chapter 2 was published with incorrect family name of the chapter author as Kobiessy.
Document Type: Erratum
Publication Stage: Final
Source: Scopus
Access Type: Open Access