“Common DNA methylation dynamics in endometriod adenocarcinoma and glioblastoma suggest universal epigenomic alterations in tumorigenesis” (2021) Communications Biology
Common DNA methylation dynamics in endometriod adenocarcinoma and glioblastoma suggest universal epigenomic alterations in tumorigenesis
(2021) Communications Biology, 4 (1), art. no. 607, .
Karlow, J.A.a , Miao, B.a b , Xing, X.a , Wang, T.a c , Zhang, B.a b
a The Edison Family Center for Genome Sciences and Systems Biology, Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
b Center of Regenerative Medicine, Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States
c McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Trends in altered DNA methylation have been defined across human cancers, revealing global loss of methylation (hypomethylation) and focal gain of methylation (hypermethylation) as frequent cancer hallmarks. Although many cancers share these trends, little is known about the specific differences in DNA methylation changes across cancer types, particularly outside of promoters. Here, we present a comprehensive comparison of DNA methylation changes between two distinct cancers, endometrioid adenocarcinoma (EAC) and glioblastoma multiforme (GBM), to elucidate common rules of methylation dysregulation and changes unique to cancers derived from specific cells. Both cancers exhibit significant changes in methylation over regulatory elements. Notably, hypermethylated enhancers within EAC samples contain several transcription factor binding site clusters with enriched disease ontology terms highlighting uterine function, while hypermethylated enhancers in GBM are found to overlap active enhancer marks in adult brain. These findings suggest that loss of original cellular identity may be a shared step in tumorigenesis. © 2021, The Author(s).
Funding details
National Institutes of HealthNIHR25DA027995, U01HG009391, U24ES026699
Foundation for the National Institutes of HealthFNIHU01CA200060, U41HG010972
American Cancer SocietyACSRSG-14-049-01-DMC
Document Type: Article
Publication Stage: Final
Source: Scopus
“Electronic clinical decision support for children with minor head trauma and intracranial injuries: a sociotechnical analysis” (2021) BMC Medical Informatics and Decision Making
Electronic clinical decision support for children with minor head trauma and intracranial injuries: a sociotechnical analysis
(2021) BMC Medical Informatics and Decision Making, 21 (1), art. no. 161, .
Greenberg, J.K.a , Otun, A.a , Nasraddin, A.b , Brownson, R.C.b , Kuppermann, N.d , Limbrick, D.D.a , Yen, P.-Y.c , Foraker, R.E.c
a Departments of Neurological Surgery, Washington University School of Medicine, 660 S. Euclid Ave., Box 8057, St. Louis, MO 63110, United States
b Brown School of Social Work, Washington University School of Medicine, St. Louis, MO, United States
c Institute for Informatics, Washington University School of Medicine, St. Louis, MO, United States
d Department of Emergency Medicine, University of California Davis, Davis, CA, United States
Abstract
Background: Current management of children with minor head trauma (MHT) and intracranial injuries is not evidence-based and may place some children at risk of harm. Evidence-based electronic clinical decision support (CDS) for management of these children may improve patient safety and decrease resource use. To guide these efforts, we evaluated the sociotechnical environment impacting the implementation of electronic CDS, including workflow and communication, institutional culture, and hardware and software infrastructure, among other factors. Methods: Between March and May, 2020 semi-structured qualitative focus group interviews were conducted to identify sociotechnical influences on CDS implementation. Physicians from neurosurgery, emergency medicine, critical care, and pediatric general surgery were included, along with information technology specialists. Participants were recruited from nine health centers in the United States. Focus group transcripts were coded and analyzed using thematic analysis. The final themes were then cross-referenced with previously defined sociotechnical dimensions. Results: We included 28 physicians and four information technology specialists in seven focus groups (median five participants per group). Five physicians were trainees and 10 had administrative leadership positions. Through inductive thematic analysis, we identified five primary themes: (1) clinical impact; (2) stakeholders and users; (3) tool content; (4) clinical practice integration; and (5) post-implementation evaluation measures. Participants generally supported using CDS to determine an appropriate level-of-care for these children. However, some had mixed feelings regarding how the tool could best be used by different specialties (e.g. use by neurosurgeons versus non-neurosurgeons). Feedback from the interviews helped refine the tool content and also highlighted potential technical and workflow barriers to address prior to implementation. Conclusions: We identified key factors impacting the implementation of electronic CDS for children with MHT and intracranial injuries. These results have informed our implementation strategy and may also serve as a template for future efforts to implement health information technology in a multidisciplinary, emergency setting. © 2021, The Author(s).
Author Keywords
Electronic clinical decision support; Head trauma; Health information technology; Implementation science; Sociotechnical analysis; Traumatic brain injury
Funding details
Agency for Healthcare Research and QualityAHRQ
Thrasher Research FundTRF
Document Type: Article
Publication Stage: Final
Source: Scopus
“Altered mapping of sound frequency to cochlear place in ears with endolymphatic hydrops provide insight into the pitch anomaly of diplacusis” (2021) Scientific Reports
Altered mapping of sound frequency to cochlear place in ears with endolymphatic hydrops provide insight into the pitch anomaly of diplacusis
(2021) Scientific Reports, 11 (1), art. no. 10380, .
Guinan, J.J., Jr.a b , Lefler, S.M.c , Buchman, C.A.c , Goodman, S.S.d , Lichtenhan, J.T.c
a Eaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA, United States
b Department of Otolaryngology, Harvard Medical School, Boston, MA, United States
c Department of Otolaryngology, School of Medicine, Washington University St. Louis, Campus Box 8115, 660 South Euclid Avenue, Saint Louis, MO 63110, United States
d Department of Communication Sciences and Disorders, University of Iowa, Iowa City, IA, United States
Abstract
A fundamental property of mammalian hearing is the conversion of sound pressure into a frequency-specific place of maximum vibration along the cochlear length, thereby creating a tonotopic map. The tonotopic map makes possible systematic frequency tuning across auditory-nerve fibers, which enables the brain to use pitch to separate sounds from different environmental sources and process the speech and music that connects us to people and the world. Sometimes a tone has a different pitch in the left and right ears, a perceptual anomaly known as diplacusis. Diplacusis has been attributed to a change in the cochlear frequency-place map, but the hypothesized abnormal cochlear map has never been demonstrated. Here we assess cochlear frequency-place maps in guinea-pig ears with experimentally-induced endolymphatic hydrops, a hallmark of Ménière’s disease. Our findings are consistent with the hypothesis that diplacusis is due to an altered cochlear map. Map changes can lead to altered pitch, but the size of the pitch change is also affected by neural synchrony. Our data show that the cochlear frequency-place map is not fixed but can be altered by endolymphatic hydrops. Map changes should be considered in assessing hearing pathologies and treatments. © 2021, The Author(s).
Funding details
National Institute on Deafness and Other Communication DisordersNIDCDR01 DC014997
Document Type: Article
Publication Stage: Final
Source: Scopus
“Probabilistic mapping of human functional brain networks identifies regions of high group consensus” (2021) NeuroImage
Probabilistic mapping of human functional brain networks identifies regions of high group consensus
(2021) NeuroImage, 237, art. no. 118164, .
Dworetsky, A.a g , Seitzman, B.A.b , Adeyemo, B.b , Neta, M.f , Coalson, R.S.a b , Petersen, S.E.a b c d e , Gratton, C.g h i
a Department of Radiology, Washington University School of Medicine, USA, United States
b Department of Neurology, Washington University School of Medicine, United States
c Department of Psychological and Brain Sciences, Washington University School of Medicine, United States
d Department of Neuroscience, Washington University School of Medicine, United States
e Department of Biomedical Engineering, Washington University School of Medicine, United States
f Department of Psychology, University of Nebraska-Lincoln, United States
g Department of Psychology, Northwestern University, United States
h Department of Neurology, Northwestern University, United States
i Interdepartmental Neuroscience Program, Northwestern University, United States
Abstract
Many recent developments surrounding the functional network organization of the human brain have focused on data that have been averaged across groups of individuals. While such group-level approaches have shed considerable light on the brain’s large-scale distributed systems, they conceal individual differences in network organization, which recent work has demonstrated to be common and widespread. This individual variability produces noise in group analyses, which may average together regions that are part of different functional systems across participants, limiting interpretability. However, cost and feasibility constraints may limit the possibility for individual-level mapping within studies. Here our goal was to leverage information about individual-level brain organization to probabilistically map common functional systems and identify locations of high inter-subject consensus for use in group analyses. We probabilistically mapped 14 functional networks in multiple datasets with relatively high amounts of data. All networks show “core” (high-probability) regions, but differ from one another in the extent of their higher-variability components. These patterns replicate well across four datasets with different participants and scanning parameters. We produced a set of high-probability regions of interest (ROIs) from these probabilistic maps; these and the probabilistic maps are made publicly available, together with a tool for querying the network membership probabilities associated with any given cortical location. These quantitative estimates and public tools may allow researchers to apply information about inter-subject consensus to their own fMRI studies, improving inferences about systems and their functional specializations. © 2021
Author Keywords
fMRI; Functional connectivity; Individual differences; Networks
Funding details
National Institutes of HealthNIHR01MH118370
James S. McDonnell FoundationJSMF
Secretaría de Educación PúblicaSEPR01MH111640
Document Type: Article
Publication Stage: Final
Source: Scopus
“Characterizing eating disorder diagnosis and related outcomes by sexual orientation and gender identity in a national sample of college students” (2021) Eating Behaviors
Characterizing eating disorder diagnosis and related outcomes by sexual orientation and gender identity in a national sample of college students
(2021) Eating Behaviors, 42, art. no. 101528, .
Grammer, A.C.a , Vázquez, M.M.a , Fitzsimmons-Craft, E.E.a , Fowler, L.A.a , Rackoff, G.N.b , Schvey, N.A.c , Lipson, S.K.d , Newman, M.G.b , Eisenberg, D.e , Taylor, C.B.f g , Wilfley, D.E.a
a Department of Psychiatry, Washington University School of Medicine, Mailstop 8134-29-2100, 660 S. Euclid Ave., St. Louis, MO 63110, United States
b Department of Psychology, The Pennsylvania State University, 371 Moore Building, University Park, PA 16802, United States
c Department of Medical and Clinical Psychology, Uniformed Services University of the Health Sciences, DoD, 4301 Jones Bridge Road, Bethesda, MD 20814, United States
d Department of Health Law Policy and Management, Boston University School of Public Health, 715 Albany Street, Talbot Building, T2W, Boston, MA 02118, United States
e Department of Health Policy and Management, Fielding School of Public Health, University of California at Los Angeles, 650 Charles E. Young Dr. South 16-035 Center for Health Sciences, Los Angeles, CA 90095, United States
f Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305, United States
g Center for m<sup>2</sup>Health, Palo Alto University, 5150 El Camino Real, Los Altos, CA 94022, United States
Abstract
Objective: In a national sample of college students, the current study aimed to: 1) examine differences in probable diagnoses of EDs (i.e., anorexia nervosa (AN), clinical/subthreshold bulimia nervosa (BN), or binge eating disorder (BED)) and weight and shape concerns by sexual orientation and gender identity, and 2) examine differences in ED chronicity and probable comorbid psychiatric diagnoses by sexual orientation and gender identity. Method: Students across nine U.S. universities completed an online screener for DSM-5 clinical or subthreshold ED diagnoses, comorbid depression and anxiety disorders, and self-reported ED chronicity. Self-reported sexual orientation and gender identity were also collected. Tukey-corrected logistic and linear regressions examined differences in outcomes separately by sexual orientation and gender identity, adjusting for age, race, and ethnicity. Results: A total of 8,531 students (24% sexually diverse (SD); 2.7% gender diverse (GD)) were studied. Students who identified as bisexual or other sexual orientation reported significantly greater odds of a probable ED diagnosis and greater elevations in weight and shape concerns compared to heterosexual students. Cisgender female students and GD students reported significantly greater odds of a probable ED diagnosis and greater elevations in weight and shape concerns compared to cisgender male students. Some SD students and GD students who met criteria for probable EDs were also more likely to report chronic ED symptoms and probable comorbid psychiatric diagnoses compared to heterosexual students and cisgender males, respectively. Discussion: Some SGD students may be at heightened risk for EDs, highlighting the need to identify mechanisms that contribute to disparities. © 2021 Elsevier Ltd
Author Keywords
College students; Comorbidities; Eating disorders; Sexual and gender diverse
Funding details
National Institute of Mental HealthNIMHR01MH115128
Document Type: Article
Publication Stage: Final
Source: Scopus
“Localizing focal brain injury via EEG spectral variance” (2021) Biomedical Signal Processing and Control
Localizing focal brain injury via EEG spectral variance
(2021) Biomedical Signal Processing and Control, 68, art. no. 102746, .
Khanmohammadi, S.a b , Laurido-Soto, O.b , Eisenman, L.N.b , Kummer, T.T.b , Ching, S.a c d
a Department of Electrical & Systems Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States
d Division of Biology and Biomedical Science, Washington University in St. Louis, St. Louis, MO 63130, United States
Abstract
In this study, we consider the problem of localizing focal brain injuries from surface electroencephalogram (EEG) recordings. To this end, we introduce a new analysis technique termed frequency-based intrinsic network dynamic reactivity (FINDR), which quantifies the extent to which different brain regions (defined in EEG channel space) are responsive to each other in terms of their frequency-domain activity. The technique generalizes the idea of EEG reactivity, a measure of how well EEG signals react/respond to exogenous stimuli. In the present work we generalize this notion to endogenous ‘stimuli,’ defined as short-time window frequency domain motifs that are most predominant on a per channel basis. For each of these predominant motifs, we quantify the variance of the activity in all other channels as a measure of ‘intrinsic reactivity’, under the hypothesis that channels proximal to injured regions will be systematically disassociated from other brain areas. We use this method as a front-end to a neural network classifier to predict injury location in a cohort of etiologically heterogeneous comatose patients. We achieve a 0.6 correlation between the predicted injury location and the actual brain injury. These results suggest a possibility of precise localization of brain injury using EEG. © 2021 Elsevier Ltd
Author Keywords
Brain injury; Electroencephalography; Injury location; Spectral variance
Funding details
National Science FoundationNSF1R21-EY027590-01, ECCS 1509342, NSF CMMI 1537015, UL1 TR000448
National Institutes of HealthNIH
Burroughs Wellcome FundBWF
Document Type: Article
Publication Stage: Final
Source: Scopus
“Sonothermogenetics for noninvasive and cell-type specific deep brain neuromodulation” (2021) Brain Stimulation
Sonothermogenetics for noninvasive and cell-type specific deep brain neuromodulation
(2021) Brain Stimulation, 14 (4), pp. 790-800.
Yang, Y.a , Pacia, C.P.a , Ye, D.b , Zhu, L.a , Baek, H.a , Yue, Y.a , Yuan, J.a , Miller, M.J.c , Cui, J.a , Culver, J.P.a d e , Bruchas, M.R.f , Chen, H.a g
a Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO 63130, United States
b Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, Saint Louis, MO 63130, United States
c Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, United States
d Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, United States
e Department of Physics, Washington University in St. Louis, Saint Louis, MO 63110, United States
f Department of Anesthesiology and Pain Medicine. Center for Neurobiology of Addiction, Pain, and Emotion. University of Washington, Seattle, WA 98195, United States
g Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, MO 63108, United States
Abstract
Background: Critical advances in the investigation of brain functions and treatment of brain disorders are hindered by our inability to selectively target neurons in a noninvasive manner in the deep brain. Objective: This study aimed to develop sonothermogenetics for noninvasive, deep-penetrating, and cell-type-specific neuromodulation by combining a thermosensitive ion channel TRPV1 with focused ultrasound (FUS)-induced brief, non-noxious thermal effect. Methods: The sensitivity of TRPV1 to FUS sonication was evaluated in vitro. It was followed by in vivo assessment of sonothermogenetics in the activation of genetically defined neurons in the mouse brain by two-photon calcium imaging. Behavioral response evoked by sonothermogenetic stimulation at a deep brain target was recorded in freely moving mice. Immunohistochemistry staining of ex vivo brain slices was performed to evaluate the safety of FUS sonication. Results: TRPV1 was found to be an ultrasound-sensitive ion channel. FUS sonication at the mouse brain in vivo selectively activated neurons that were genetically modified to express TRPV1. Temporally precise activation of TRPV1-expressing neurons was achieved with its success rate linearly correlated with the peak temperature within the FUS-targeted brain region as measured by in vivo magnetic resonance thermometry. FUS stimulation of TRPV1-expressing neurons at the striatum repeatedly evoked locomotor behavior in freely moving mice. FUS sonication was confirmed to be safe based on inspection of neuronal integrity, inflammation, and apoptosis markers. Conclusions: This noninvasive and cell-type-specific neuromodulation approach with the capability to stimulate deep brain has the promise to advance the study of the intact nervous system and uncover new ways to treat neurological disorders. © 2021 The Author(s)
Author Keywords
Calcium imaging; Focused ultrasound; Ion channel; Neuromodulation; Sonothermogenetics
Funding details
National Institutes of HealthNIHR01MH116981
National Institute of Biomedical Imaging and BioengineeringNIBIBR01EB027223, R01EB030102
University of WashingtonUW
Document Type: Article
Publication Stage: Final
Source: Scopus
“BRAF-MEK inhibitors as steroid-sparing bridge prior to checkpoint blockade therapy in symptomatic intracranial melanoma” (2021) Melanoma Management
BRAF-MEK inhibitors as steroid-sparing bridge prior to checkpoint blockade therapy in symptomatic intracranial melanoma
(2021) Melanoma Management, 8 (2), art. no. 0022, .
Khaddour, K., Johanns, T.M., Ansstas, G.
Department of Medicine, Division of Medical Oncology, Washington University School of Medicine, Saint Louis, MO 63110, United States
Abstract
The introduction of immune checkpoint blockade (ICB) and BRAF-MEK inhibitors has substantially improved outcomes in patients with metastatic melanoma. However, several challenging factors may hinder the efficacy of ICB in patients with symptomatic intracranial metastatic melanoma who are immunosuppressed due to the use of steroids prior to the administration of ICB. This has resulted in the exclusion of patients treated with high dose steroid at baseline from the majority of ICB clinical trials. In addition, despite the high efficacy of BRAF-MEK inhibitors in BRAF-mutant intracranial metastatic melanoma, most tumors will eventually progress. This demonstrates a gap in addressing the best management in such patients. Here, we present a case demonstrating our approach in this patient population. © 2021 Future Medicine Ltd.. All rights reserved.
Author Keywords
BRAF-MEK; brain; immune checkpoint blockade; intracranial; ipilimumab; metastatic melanoma; nivolumab; steroids; symptomatic; targeted therapy
Document Type: Article
Publication Stage: Final
Source: Scopus
“Temporal and spectral unmixing of photoacoustic signals by deep learning” (2021) Optics Letters
Temporal and spectral unmixing of photoacoustic signals by deep learning
(2021) Optics Letters, 46 (11), pp. 2690-2693.
Zhou, Y., Zhong, F., Hu, S.
Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States
Abstract
Improving the imaging speed of multi-parametric photoacoustic microscopy (PAM) is essential to leveraging its impact in biomedicine.However, to avoid temporal overlap, the A-line rate is limited by the acoustic speed in biological tissues to a few megahertz.Moreover, to achieve high-speed PAMof the oxygen saturation of hemoglobin, the stimulated Raman scattering effect in optical fibers has been widely used to generate 558 nm from a commercial 532 nm laser for dual-wavelength excitation. However, the fiber length for effective wavelength conversion is typically short, corresponding to a small time delay that leads to a significant overlap of the A-lines acquired at the two wavelengths. Increasing the fiber length extends the time interval but limits the pulse energy at 558 nm. In this Letter, we report a conditional generative adversarial network-based approach that enables temporal unmixing of photoacoustic A-line signals with an interval as short as ~38 ns, breaking the physical limit on the A-line rate. Moreover, this deep learning approach allows the use of multi-spectral laser pulses for PAM excitation, addressing the insufficient energy of monochromatic laser pulses. This technique lays the foundation for ultrahigh-speed multi-parametric PAM. © 2021 Optical Society of America.
Funding details
National Science FoundationNSF2023988
National Institutes of HealthNIHNS099261
Document Type: Article
Publication Stage: Final
Source: Scopus
“Long-term inflammatory pain does not impact exploratory behavior and stress coping strategies in mice” (2021) Pain
Long-term inflammatory pain does not impact exploratory behavior and stress coping strategies in mice
(2021) Pain, 162 (6), pp. 1705-1721.
Burek, D.J.a b c , Massaly, N.a c , Doering, M.d , Zec, A.a c , Gaelen, J.a c , Morón, J.A.a b c e
a Departments of Anesthesiology and
b Neuroscience, Washington University in St. Louis, St. Louis, MO, United States
c Washington University Pain Center Basic Research Division, St. Louis, MO, United States
d Bernard Becker Medical Library, Washington University School of Medicine, St. Louis, MO, United States
e Department of Psychiatry, Washington University in St. Louis, St. Louis, MO, United States
Abstract
ABSTRACT: Pain puts patients at risk for developing psychiatric conditions such as anxiety and depression. Preclinical mouse models of pain-induced affective behavior vary widely in methodology and results, impairing progress towards improved therapeutics. To systematically investigate the effect of long-term inflammatory pain on exploratory behavior and stress coping strategy, we assessed male C57BL/6J mice in the forced swim test (FST), elevated zero maze, and open field test at 4 and 6 weeks postinjection of Complete Freund’s Adjuvant, while controlling for testing order and combination. Inflammatory pain did not induce a passive stress coping strategy in the FST and did not reduce exploratory behavior in the elevated zero maze or the open field test. Using systematic correlational analysis and composite behavioral scores, we found no consistent association among measures for mice with or without inflammatory pain. A meta-analysis of similar studies indicated a modest, significant effect of Complete Freund’s Adjuvant on exploratory behavior, but not immobility in the FST, and high heterogeneity among effect sizes in all 3 paradigms. Given the urgency for understanding the mechanisms of pain comorbidities and identifying novel therapies, these findings support the reallocation of our limited resources away from such unreliable assays and toward motivated and naturalistic behaviors. Future studies in pain and psychiatric translational research may benefit by considering outcomes beyond binary categorization, quantifying the associations between multiple measured behaviors, and agnostically identifying subtle yet meaningful patterns in behaviors. Copyright © 2021 International Association for the Study of Pain.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Investigating Predictors of Increased Length of Stay After Resection of Vestibular Schwannoma Using Machine Learning” (2021) Otology & Neurotology: Official Publication of the American Otological Society, American Neurotology Society and European Academy of Otology and Neurotology
Investigating Predictors of Increased Length of Stay After Resection of Vestibular Schwannoma Using Machine Learning
(2021) Otology & Neurotology: Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 42 (5), pp. e584-e592.
Dang, S.a , Manzoor, N.F.b , Chowdhury, N.c , Tittman, S.M.c , Yancey, K.L.c , Monsour, M.A.d , O’Malley, M.R.c , Rivas, A.b , Haynes, D.S.c , Bennett, M.L.c
a Department of Otolaryngology – Head and Neck Surgery, Washington University, St. Louis, MO, United States
b Department of Otolaryngology – Head and Neck Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
c Department of Otolaryngology – Head and Neck Surgery, Vanderbilt University Medical Center
d Vanderbilt University School of Medicine, Nashville, TN, United States
Abstract
OBJECTIVE: To evaluate the predictors of prolonged length of stay (LOS) after vestibular schwannoma resection. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Patients who underwent vestibular schwannoma resection between 2008 and 2019. INTERVENTIONS: Variables of interest included age, body mass index, comorbidities, symptoms, previous intervention, microsurgical approach, extent of resection, operative time, preoperative tumor volume, and postoperative complications. Predictive modeling was done through multivariable linear regression and random forest models with 80% of patients used for model training and the remaining 20% used for performance testing. MAIN OUTCOME MEASURES: LOS was evaluated as the number of days from surgery to discharge. RESULTS: Four hundred one cases from 2008 to 2019 were included with a mean LOS of 3.0 (IQR = 3.0-4.0). Postoperatively, 14 (3.5%) of patients had LOS greater than two standard deviations from the mean (11 days). In a multivariate linear regression model (adjusted R2 = 0.22; p < 0.001), preoperative tumor volume (p < 0.001), coronary artery disease (p = 0.002), hypertension (p = 0.029), and any major complication (p < 0.001) were associated with increased LOS (by 0.12, 3.79, 0.87, and 3.20 days respectively). A machine learning analysis using a random forest identified several potential nonlinear relationships between LOS and preoperative tumor dimensions (length, volume) and operative time that were not captured on regression. The random forest model had lower prediction error compared to the regression model (RMSE 5.67 vs. 44.59). CONCLUSIONS: Tumor volume, coronary artery disease, hypertension, and major complications impact LOS. Machine learning methods may identify nonlinear relationships worthy of targeted clinical investigation and allow for more accurate patient counseling. Copyright © 2020, Otology & Neurotology, Inc.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Simultaneous imaging of amyloid deposition and cerebrovascular function using dual-contrast photoacoustic microscopy” (2021) Optics Letters
Simultaneous imaging of amyloid deposition and cerebrovascular function using dual-contrast photoacoustic microscopy
(2021) Optics Letters, 46 (11), pp. 2561-2564.
Zhou, Y.a , Zhong, F.a , Yan, P.b , Lee, J.-M.a b , Hu, S.a
a Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Pathological aggregation of Aβ peptides results in the deposition of amyloid in the brain parenchyma (senile plaques in Alzheimer’s disease [AD]) and around cerebral microvessels (cerebral amyloid angiopathy [CAA]). Our current understanding of the amyloid-induced microvascular changes has been limited to the structure and hemodynamics—leaving the oxygen-metabolic aspect unattended. In this Letter, we report a dual-contrast photoacoustic microscopy (PAM) technique, which integrates the molecular contrast of dichroism PAM and the physiological contrast of multi-parametric PAM for simultaneous, intravital imaging of amyloid deposition and cerebrovascular function in a mouse model that develops AD and CAA. This technique opens up new opportunities to study the spatiotemporal interplay between amyloid deposition and vascular-metabolic dysfunction in AD and CAA. © 2021 Optical Society of America
Document Type: Article
Publication Stage: Final
Source: Scopus
“Elementary mechanisms of calmodulin regulation of NaV1.5 producing divergent arrhythmogenic phenotypes” (2021) Proceedings of the National Academy of Sciences of the United States of America
Elementary mechanisms of calmodulin regulation of NaV1.5 producing divergent arrhythmogenic phenotypes
(2021) Proceedings of the National Academy of Sciences of the United States of America, 118 (21), .
Kang, P.W.a b , Chakouri, N.c , Diaz, J.c , Tomaselli, G.F.d , Yue, D.T.e , Ben-Johny, M.c f
a Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218; mbj2124@cumc.columbia.edu
b Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130
c Department of Physiology and Cellular Biophysics, Columbia University, NY, NY 10032
d Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461
e Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, United States
f Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218; kang.powei@wustl.edu mbj2124@cumc.columbia.edu
Abstract
In cardiomyocytes, NaV1.5 channels mediate initiation and fast propagation of action potentials. The Ca2+-binding protein calmodulin (CaM) serves as a de facto subunit of NaV1.5. Genetic studies and atomic structures suggest that this interaction is pathophysiologically critical, as human mutations within the NaV1.5 carboxy-terminus that disrupt CaM binding are linked to distinct forms of life-threatening arrhythmias, including long QT syndrome 3, a “gain-of-function” defect, and Brugada syndrome, a “loss-of-function” phenotype. Yet, how a common disruption in CaM binding engenders divergent effects on NaV1.5 gating is not fully understood, though vital for elucidating arrhythmogenic mechanisms and for developing new therapies. Here, using extensive single-channel analysis, we find that the disruption of Ca2+-free CaM preassociation with NaV1.5 exerts two disparate effects: 1) a decrease in the peak open probability and 2) an increase in persistent NaV openings. Mechanistically, these effects arise from a CaM-dependent switch in the NaV inactivation mechanism. Specifically, CaM-bound channels preferentially inactivate from the open state, while those devoid of CaM exhibit enhanced closed-state inactivation. Further enriching this scheme, for certain mutant NaV1.5, local Ca2+ fluctuations elicit a rapid recruitment of CaM that reverses the increase in persistent Na current, a factor that may promote beat-to-beat variability in late Na current. In all, these findings identify the elementary mechanism of CaM regulation of NaV1.5 and, in so doing, unravel a noncanonical role for CaM in tuning ion channel gating. Furthermore, our results furnish an in-depth molecular framework for understanding complex arrhythmogenic phenotypes of NaV1.5 channelopathies.
Author Keywords
Brugada syndrome; calmodulin; ion channels; long QT syndrome; Nav1.5
Document Type: Article
Publication Stage: Final
Source: Scopus
“Cell-autonomous retinoic acid receptor signaling has stage-specific effects on mouse enteric nervous system” (2021) JCI Insight
Cell-autonomous retinoic acid receptor signaling has stage-specific effects on mouse enteric nervous system
(2021) JCI Insight, 6 (10), art. no. e145854, .
Gao, T.a , Wright-Jin, E.C.b , Sengupta, R.a , Anderson, J.B.a , Heuckeroth, R.O.a b c
a Children’s Hospital of Philadelphia Research Institute, Philadelphia, PA, United States
b Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
c Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
Abstract
Retinoic acid (RA) signaling is essential for enteric nervous system (ENS) development, since vitamin A deficiency or mutations in RA signaling profoundly reduce bowel colonization by ENS precursors. These RA effects could occur because of RA activity within the ENS lineage or via RA activity in other cell types. To define cell-autonomous roles for retinoid signaling within the ENS lineage at distinct developmental time points, we activated a potent floxed dominant-negative RA receptor α (RarαDN) in the ENS using diverse CRE recombinase–expressing mouse lines. This strategy enabled us to block RA signaling at premigratory, migratory, and postmigratory stages for ENS precursors. We found that cell-autonomous loss of RA receptor (RAR) signaling dramatically affected ENS development. CRE activation of RarαDN expression at premigratory or migratory stages caused severe intestinal aganglionosis, but at later stages, RarαDN induced a broad range of phenotypes including hypoganglionosis, submucosal plexus loss, and abnormal neural differentiation. RNA sequencing highlighted distinct RA-regulated gene sets at different developmental stages. These studies show complicated context-dependent RA-mediated regulation of ENS development. Copyright: © 2021, Gao et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
Funding details
MD-II2013-269, R01 DK087715
Burroughs Wellcome FundBWF1008525
Document Type: Article
Publication Stage: Final
Source: Scopus
“Prospective Quantification of CSF Biomarkers in Antibody-Mediated Encephalitis” (2021) Neurology
Prospective Quantification of CSF Biomarkers in Antibody-Mediated Encephalitis
(2021) Neurology, 96 (20), pp. e2546-e2557.
Day, G.S., Yarbrough, M.Y., Körtvelyessy, P., Prüss, H., Bucelli, R.C., Fritzler, M.J., Mason, W., Tang-Wai, D.F., Steriade, C., Hébert, J., Henson, R.L., Herries, E.M., Ladenson, J.H., Lopez-Chiriboga, A.S., Graff-Radford, N.R., Morris, J.C., Fagan, A.
From the Department of Neurology (G.S.D., A.S.L.-C., N.R.G.-R.), Mayo Clinic, Jacksonville, FL; Departments of Pathology and Immunology (M.Y.Y., E.M.H., J.H.L.) and Neurology (R.C.B., R.L.H., E.M.H., J.H.L., J.C.M., A.F.) and The Charles F. and Joanne Knight Alzheimer Disease Research Center (R.L.H., J.C.M., A.F.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (P.M.D.K.), University of Magdeburg; Department of Neurology and Experimental Neurology (P.M.D.K., H.P.) Charité, Universitätmedizin Berlin, Germany; Department of Medicine (M.J.F.), Cumming School of Medicine, University of Calgary; Department of Medicine (W.M., D.F.T.-W., J.H.), Division of Neurology, University of Toronto, Canada; and NYU Langone Comprehensive Epilepsy Center (C.S.), NYU Langone Health, New York, NY
Abstract
OBJECTIVE: To determine whether neuronal and neuroaxonal injury, neuroinflammation, and synaptic dysfunction associate with clinical course and outcomes in antibody-mediated encephalitis (AME), we measured biomarkers of these processes in CSF from patients presenting with AME and cognitively normal individuals. METHODS: Biomarkers of neuronal (total tau, VILIP-1) and neuroaxonal damage (neurofilament light chain [NfL]), inflammation (YKL-40), and synaptic function (neurogranin, SNAP-25) were measured in CSF obtained from 45 patients at the time of diagnosis of NMDA receptor (n = 34) or LGI1/CASPR2 (n = 11) AME and 39 age- and sex-similar cognitively normal individuals. The association between biomarkers and modified Rankin Scale (mRS) scores were evaluated in a subset (n = 20) of longitudinally followed patients. RESULTS: Biomarkers of neuroaxonal injury (NfL) and neuroinflammation (YKL-40) were elevated in AME cases at presentation, whereas markers of neuronal injury and synaptic function were stable (total tau) or decreased (VILIP-1, SNAP-25, neurogranin). The log-transformed ratio of YKL-40/SNAP-25 optimally discriminated patients from cognitively normal individuals (area under the receiver operating characteristic curve 0.99; 95% confidence interval 0.97, >0.99). Younger age (ρ = -0.56; p = 0.01), lower VILIP-1 (ρ = -0.60; p < 0.01) and SNAP-25 (ρ = -0.54; p = 0.01), and higher log10(YKL-40/SNAP-25) (ρ = 0.48; p = 0.04) associated with greater disease severity (higher mRS score) in prospectively followed patients. Higher YKL-40 (ρ = 0.60; p = 0.02) and neurogranin (ρ = 0.55; p = 0.03) at presentation were associated with higher mRS scores 12 months following hospital discharge. CONCLUSIONS: CSF biomarkers suggest that neuronal integrity is acutely maintained in AME, despite neuroaxonal compromise. Low levels of biomarkers of synaptic function may reflect antibody-mediated internalization of cell surface receptors and may represent an acute correlate of antibody-mediated synaptic dysfunction, with the potential to inform disease severity and outcomes. © 2021 American Academy of Neurology.
Document Type: Article
Publication Stage: Final
Source: Scopus
“EAAT5 Glutamate Transporter-Mediated Inhibition in the Vertebrate Retina” (2021) Frontiers in Cellular Neuroscience
EAAT5 Glutamate Transporter-Mediated Inhibition in the Vertebrate Retina
(2021) Frontiers in Cellular Neuroscience, 15, art. no. 662859, .
Lukasiewcz, P.D.a b , Bligard, G.W.a , DeBrecht, J.D.a
a Department of Ophthalmology Visual Sciences, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
b Department of Neuroscience, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
Abstract
Glutamate transporters typically remove glutamate from the synaptic cleft. In addition, all glutamate transporters have a chloride channel, which is opened upon glutamate binding to the transporter. There are five types of glutamate transporter (EAATs 1–5, excitatory amino acid transporters), which have distinct chloride conductances. Some EAATs that have low chloride conductances, remove glutamate from the synaptic cleft most effectively (e.g., EAAT1). By contrast, EAATs that have high chloride conductances, remove glutamate less effectively (e.g., EAAT5). We have studied EAAT5 in the retina. In the retina, light activates a chloride current, mediated by the glutamate activation of EAAT5. EAAT5 is not a significant contributor to lateral inhibition in the retina. Instead, it is the main source of autoinhibition to rod bipolar cells (RBCs). EAAT5-mediated inhibition has a substantial effect on synaptic transmission from RBCs to downstream retinal neurons. © Copyright © 2021 Lukasiewcz, Bligard and DeBrecht.
Author Keywords
EAAT5; glutamate; inhibition; light-response; retina; transporter
Funding details
National Eye InstituteNEIEY013360, EY02687, EY08922
Research to Prevent BlindnessRPB
Document Type: Review
Publication Stage: Final
Source: Scopus
“Prediction of suicidal ideation and attempt in 9 and 10 year-old children using transdiagnostic risk features” (2021) PLoS ONE
Prediction of suicidal ideation and attempt in 9 and 10 year-old children using transdiagnostic risk features
(2021) PLoS ONE, 16 (5 May), art. no. e0252114, .
Harman, G.a b , Kliamovich, D.c , Morales, A.M.b , Gilbert, S.b , Barch, D.M.d , Mooney, M.A.a , Ewing, S.W.F.e , Fair, D.A.f , Nagel, B.J.b c
a Department of Medical Informatics and Computational Epidemiology, Oregon Health and Science University, Portland, OR, United States
b Department of Psychiatry, Oregon Health and Science University, Portland, OR, United States
c Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, United States
d Departments of Psychological & Brain Sciences, Psychiatry, Radiology, Washington University, St. Louis, MO, United States
e Department of Psychology, University of Rhode Island, Kingston, RI, United States
f Department of Pediatrics and Institute of Child Development, University of Minnesota, Minneapolis, MN, United States
Abstract
The objective of the current study was to build predictive models for suicidal ideation in a sample of children aged 9-10 using features previously implicated in risk among older adolescent and adult populations. This case-control analysis utilized baseline data from the Adolescent Brain and Cognitive Development (ABCD) Study, collected from 21 research sites across the United States (N = 11,369). Several regression and ensemble learning models were compared on their ability to classify individuals with suicidal ideation and/or attempt from healthy controls, as assessed by the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version. When comparing control participants (mean age: 9.92±0.62 years; 4944 girls [49%]) to participants with suicidal ideation (mean age: 9.89±0.63 years; 451 girls [40%]), both logistic regression with feature selection and elastic net without feature selection predicted suicidal ideation with an AUC of 0.70 (CI 95%: 0.70-0.71). The random forest with feature selection trained to predict suicidal ideation predicted a holdout set of children with a history of suicidal ideation and attempt (mean age: 9.96±0.62 years; 79 girls [41%]) from controls with an AUC of 0.77 (CI 95%: 0.76-0.77). Important features from these models included feelings of loneliness and worthlessness, impulsivity, prodromal psychosis symptoms, and behavioral problems. This investigation provided an unprecedented opportunity to identify suicide risk in youth. The use of machine learning to examine a large number of predictors spanning a variety of domains provides novel insight into transdiagnostic factors important for risk classification Copyright: © 2021 Harman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Aging-associated deficit in CCR7 is linked to worsened glymphatic function, cognition, neuroinflammation, and β-amyloid pathology” (2021) Science Advances
Aging-associated deficit in CCR7 is linked to worsened glymphatic function, cognition, neuroinflammation, and β-amyloid pathology
(2021) Science Advances, 7 (21), art. no. eabe4601, .
Mesquita, S.D.a , Herz, J.b c , Wall, M.a , Dykstra, T.b c , de Lima, K.A.b c , Norris, G.T.d , Dabhi, N.a , Kennedy, T.a , Baker, W.a , Kipnis, J.a b c
a Department of Neuroscience, Center for Brain Immunology and Glia (BIG), University of Virginia, Charlottesville, VA, United States
b Center for Brain Immunology and Glia (BIG), Washington University in St. Louis, St. Louis, MO, United States
c Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
d Department of Immunology, University of Washington, Seattle, WA 98109, United States
Abstract
Aging leads to a progressive deterioration of meningeal lymphatics and peripheral immunity, which may accelerate cognitive decline. We hypothesized that an age-related reduction in C-C chemokine receptor type 7 (CCR7)–dependent egress of immune cells through the lymphatic vasculature mediates some aspects of brain aging and potentially exacerbates cognitive decline and Alzheimer’s disease–like brain β-amyloid (Aβ) pathology. We report a reduction in CCR7 expression by meningeal T cells in old mice that is linked to increased effector and regulatory T cells. Hematopoietic CCR7 deficiency mimicked the aging-associated changes in meningeal T cells and led to reduced glymphatic influx and cognitive impairment. Deletion of CCR7 in 5xFAD transgenic mice resulted in deleterious neurovascular and microglial activation, along with increased Aβ deposition in the brain. Treating old mice with anti-CD25 antibodies alleviated the exacerbated meningeal regulatory T cell response and improved cognitive function, highlighting the therapeutic potential of modulating meningeal immunity to fine-tune brain function in aging and in neurodegenerative diseases. © 2021 The Authors, some rights reserved;
Document Type: Article
Publication Stage: Final
Source: Scopus
“Sex-related Differences in Tau Positron Emission Tomography (PET) and the Effects of Hormone Therapy (HT)” (2021) Alzheimer Disease and Associated Disorders
Sex-related Differences in Tau Positron Emission Tomography (PET) and the Effects of Hormone Therapy (HT)
(2021) Alzheimer Disease and Associated Disorders, 35 (2), pp. 164-168. Cited 2 times.
Wisch, J.K.a , Meeker, K.L.a , Gordon, B.A.a , Flores, S.a , Dincer, A.a , Grant, E.A.b c , Benzinger, T.L.c d , Morris, J.C.a c , Ances, B.M.a c d
a Departments of Neurology
b Biostatistics
c Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO
d Radiology, Washington University in St. Louis
Abstract
IMPORTANCE: Female sex is a major risk factor for late-onset Alzheimer disease (AD), and sex hormones have been implicated as a possible protective factor. Neuroimaging studies that evaluated the effects of sex hormones on brain integrity have primarily emphasized neurodegenerative measures rather than amyloid and tau burden. OBJECTIVE: We compared cortical amyloid and regional tau positron emission tomography (PET) deposition between cognitively normal males and females. We also compared preclinical AD pathology between females who have and have not used hormone therapy (HT). Finally, we compared the effects of amyloid and tau pathology on cognition, testing for both sex and HT effects. DESIGN, SETTING, AND PARTICIPANTS: We analyzed amyloid, tau, and cognition in a cognitively normal cross-sectional cohort of older individuals (n=148) followed at the Knight Alzheimer Disease Research Center. Amyloid and tau PET, medication history, and neuropsychological testing were obtained for each participant. RESULTS: Within cognitively normal individuals, there was no difference in amyloid burden by sex. Whether or not we controlled for amyloid burden, female participants had significantly higher tau PET levels than males in multiple regions, including the rostral middle frontal and superior and middle temporal regions. HT accounted for a small reduction in tau PET; however, males still had substantially lower tau PET compared with females. Amyloid PET and tau PET burden were negatively associated with cognitive performance, although increasing amyloid PET did not have a deleterious effect on cognitive performance for women with a history of HT. CONCLUSIONS AND RELEVANCE: Regional sex-related differences in tau PET burden may contribute to the disparities in AD prevalence between males and females. The observed decreases tau PET burden in HT users has important implications for clinical practice and trials and deserves future consideration in longitudinal studies. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Racial Associations Between Gambling and Suicidal Behaviors Among Black and White Adolescents and Young Adults” (2021) Current Addiction Reports
Racial Associations Between Gambling and Suicidal Behaviors Among Black and White Adolescents and Young Adults
(2021) Current Addiction Reports, .
Ahuja, M.a , Werner, K.B.b , Cunningham-Williams, R.M.c , Bucholz, K.K.d
a Department of Health Services Management and Policy, East Tennessee State University, Johnson City, TN 37604, United States
b College of Nursing, University of Missouri at St. Louis, St. Louis, MO, United States
c Brown School of Social Work, Washington University in St. Louis, St. Louis, MO, United States
d Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Purpose of Review: Suicide is the second leading cause of death among Black youth ages 10–19 years. Between 1991 and 2017, rates of suicide among Black youth have been increasing faster than rates among any other race/ethnic group. There are many factors that may explain this increase, with gambling being suggested as one such potential risk factor. This review examines the association between gambling and suicide behaviors, and how these associations may vary between Black and White youth and young adults. The current review examines these associations using data from the Missouri Family Study (MOFAM). Recent Findings: Recent findings have revealed distinct patterns of substance use initiation and gambling behaviors between Black youth and White youth. While strong links between gambling and suicide behaviors have also been reported, whether the associations were consistent across race/ethnicity groups was not investigated, nor in these cross-sectional analyses was it possible to determine whether the gambling behaviors preceded or followed suicidality. Thus, there is a need to investigate whether there are differences in the associations of gambling and suicide behaviors at the race/ethnicity level in tandem with data that examine the sequence of the behaviors. The current report focuses on racial/ethnic differences using data that allow for sequencing the occurrence of the behaviors via the age of first gambling experience, and of first suicidal symptom, to better distinguish the nature of the association. Summary: The current findings revealed that gambling initiation predicted suicide ideation among Black youth, while no significant association was found among White youth. This is of major public health concern, given the rising rates of suicide among Black youth, and the increased availability of gambling. The report did not find a link between gambling and suicide attempts. Culturally tailored interventions should be considered among schools, families, and clinicians/providers, to highlight the risk of adolescent gambling, particularly among Black youth. © 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Author Keywords
Adolescent gambling; African American gambling; Black youth suicide; Gambling among Black youth; Gambling and suicide; Gambling risk
Document Type: Review
Publication Stage: Article in Press
Source: Scopus
“Undetected Neurodegenerative Disease Biases Estimates of Cognitive Change in Older Adults” (2021) Psychological Science
Undetected Neurodegenerative Disease Biases Estimates of Cognitive Change in Older Adults
(2021) Psychological Science, .
Harrington, K.D.a b c , Aschenbrenner, A.J.d e , Maruff, P.a f , Masters, C.L.a , Fagan, A.M.d e g , Benzinger, T.L.S.d h i , Gordon, B.A.d g h , Cruchaga, C.j k , Morris, J.C.d e l m n , Hassenstab, J.d e o
a The Florey Institute, The University of Melbourne, Australia
b Cooperative Research Centre for Mental Health, Parkville, VIC, Australia
c Center for Healthy Aging, The Pennsylvania State University, United States
d Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St. Louis, United States
e Department of Neurology, Washington University in St. Louis, United States
f CogState, Melbourne, VIC, Australia
g Hope Center for Neurological Disorders, Washington University in St. Louis, United States
h Department of Radiology, Washington University in St. Louis, United States
i Department of Neurological Surgery, Washington University in St. Louis, United States
j Department of Psychiatry, Washington University in St. Louis, United States
k Department of Developmental Biology, Washington University in St. Louis, United States
l Department of Pathology and Immunology, Washington University in St. Louis, United States
m Department of Physical Therapy, Washington University in St. Louis, United States
n Department of Occupational Therapy, Washington University in St. Louis, United States
o Department of Psychological & Brain Sciences, Washington University in St. Louis, United States
Abstract
Neurodegenerative disease is highly prevalent among older adults and, if undetected, may obscure estimates of cognitive change among aging samples. Our aim in this study was to determine the nature and magnitude of cognitive change in the absence of common neuropathologic markers of neurodegenerative disease. Cognitively normal older adults (ages 65–89 years, N = 199) were classified as normal or abnormal using neuroimaging and cerebrospinal-fluid biomarkers of β-amyloid, tau, and neurodegeneration. When cognitive change was modeled without accounting for biomarker status, significant decline was evident for semantic memory, processing speed, and working memory. However, after adjusting for biomarker status, we found that the rate of change was attenuated and that the biomarker-normal group demonstrated no decline for any cognitive domain. These results indicate that estimates of cognitive change in otherwise healthy older adults will be biased toward decline when the presence of early neurodegenerative disease is not accounted for. © The Author(s) 2021.
Author Keywords
cognitive aging; memory; neurodegeneration; processing speed; tau; β-amyloid
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Responsible Use of Open-Access Developmental Data: The Adolescent Brain Cognitive Development (ABCD) Study” (2021) Psychological Science
Responsible Use of Open-Access Developmental Data: The Adolescent Brain Cognitive Development (ABCD) Study
(2021) Psychological Science, .
Simmons, C.a , Conley, M.I.a , Gee, D.G.a , Baskin-Sommers, A.a , Barch, D.M.b c d , Hoffman, E.A.e , Huber, R.S.f , Iacono, W.G.g h i , Nagel, B.J.j k , Palmer, C.E.l , Sheth, C.S.f , Sowell, E.R.m , Thompson, W.K.n , Casey, B.J.a
a Department of Psychology, Yale University, United States
b Department of Psychological & Brain Sciences, Washington University in St. Louis, United States
c Department of Psychiatry, Washington University in St. Louis, United States
d Department of Radiology, Washington University in St. Louis, United States
e National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, United States
f Department of Psychiatry, University of Utah, School of Medicine, United States
g Department of Psychology, University of Minnesota, United States
h Department of Psychiatry, University of Minnesota, United States
i Department of Neuroscience, University of Minnesota, United States
j Department of Psychiatry, Oregon Health Science University, United States
k Department of Behavioral Neuroscience, Oregon Health Science University, United States
l Center for Human Development, University of California San Diego, United States
m Department of Pediatrics, Children’s Hospital Los Angeles, University of Southern California, United States
n The Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, United States
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Non-Vitamin K Antagonist Oral Anticoagulants for the Treatment of Cerebral Venous Sinus Thrombosis: a Retrospective, Matched Cohort Analysis” (2021) Neurocritical Care
Non-Vitamin K Antagonist Oral Anticoagulants for the Treatment of Cerebral Venous Sinus Thrombosis: a Retrospective, Matched Cohort Analysis
(2021) Neurocritical Care, .
Giles, J.A.a , Balasetti, V.K.S.b , Zazulia, A.R.a c
a Department of Neurology, Washington University School of Medicine in St. Louis, 660 S. Euclid Ave., Campus Box 8111, St. Louis, MO 63110, United States
b Baptist Medical Center South, Montgomery, AL, United States
c Department of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
Abstract
Background: The management of cerebral venous sinus thrombosis (CVT) is a common problem facing vascular neurologists. American Heart Association/American Stroke Association guidelines suggest the use of heparin followed by vitamin K antagonists (VKAs) for anticoagulation in CVT. In recent years, the evidence base has solidified for the use of non-vitamin K antagonist oral anticoagulants (NOACs) in lower extremity deep vein thrombosis. Because data supporting their use in CVT are limited, with the strongest evidence comprising one randomized controlled trial of dabigatran, we sought to review our experience with NOACs in the treatment of CVT at a tertiary care center to address efficacy and safety. Methods: We retrospectively reviewed charts of all patients with CVT treated with an NOAC at our tertiary care facility in the years 2011–2019. We collected data on demographics, risk factors for CVT, clinical features at presentation, imaging results, anticoagulation regimen, bleeding complications, and disability at follow-up. We compared disability at follow-up and major hemorrhagic events with age-matched and sex-matched controls treated with VKAs over the same time period and with historical controls. Results: We identified 29 patients with CVT treated with an NOAC, 27 of whom had follow-up within our system. NOACs that were used for treatment included apixaban (20 patients), rivaroxaban (6 patients) and dabigatran (1 patient). NOAC use was associated with stabilization of a clot or partial recanalization in 55.6% of patients and complete recanalization in 14.8% at a median follow-up time of 6 months. The median modified Rankin Score (mRS) at follow-up was 0, with one death. Three patients (11.1%) had major bleeding complications, including two with symptomatic worsening of intracranial hemorrhage. Comparisons of 27 age-matched and sex-matched controls treated with VKAs showed no significant differences in terms of partial recanalization (55.6% vs. 63.0%, p = 0.29), complete recanalization (14.8% vs. 25.9%, p = 0.73), mRS at follow-up (median 0 vs. 0, p = 0.23), or major bleeding (11.1% vs. 11.1%, p > 0.99). Comparisons with the historical International Study on Cerebral Vein and Dural Sinus Thrombosis cohort showed similar functional outcomes: 92.6% of patients treated with NOACs and 88.9% of patients treated with VKAs at the Washington University School of Medicine in St. Louis, as well as 86.2% of patients treated with VKAs in the historical study cohort, had mRS of 0–2 at follow-up (p = 0.60). Rates of major bleeding compared with this cohort were also similar (11.1% vs. 11.1% vs. 14.5%, p = 0.80). Conclusions: The safety and efficacy results of NOAC use for CVT were similar to those for age-matched and sex-matched controls treated with VKAs, as well as historical published controls. Assessment of NOAC efficacy and safety in CVT in multicenter cohort studies and randomized controlled trials is warranted. © 2021, Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.
Author Keywords
Anticoagulants; Cerebrovascular disorders; Factor Xa inhibitors; Sinus thrombosis (intracranial)
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“PedsQL Multiple Sclerosis Module Domain and Item Development: Qualitative Methods” (2021) Journal of Child Neurology
PedsQL Multiple Sclerosis Module Domain and Item Development: Qualitative Methods
(2021) Journal of Child Neurology, .
Gaudioso, C.a , Oo, S.a , Mar, S.a , Hendricks-Ferguson, V.L.b , Newland, P.c , Varni, J.W.d
a Department of Neurology, Division of Pediatric Neurology, Washington University School of Medicine, St Louis, MO, United States
b Trudy Busch Valentine School of Nursing, Saint Louis University, St Louis, MO, United States
c Goldfarb School of Nursing, Barnes Jewish College, St Louis, MO, United States
d Department of Pediatrics, College of Medicine, Department of Landscape Architecture and Urban Planning, College of Architecture, Texas AM University, College Station, TX, United States
Abstract
Background: The objective of this qualitative methods study was to develop the domains and items to support the content validity for the Pediatric Quality of Life Inventory (PedsQL) Multiple Sclerosis Module for youth with pediatric-onset multiple sclerosis. Methods: A literature review of multiple sclerosis–specific questionnaires and clinical research was conducted to generate domains. An expert panel composed of 12 neurologists who were pediatric-onset multiple sclerosis specialists provided feedback on the conceptual framework. Focus interviews with 9 youth with pediatric-onset multiple sclerosis and 6 parents were conducted to develop the relevant domains and item content from the patient and parent perspective. In the cognitive interviews phase, 9 youth with pediatric-onset multiple sclerosis and 6 parents provided feedback on item content, relevance, importance, and understandability of the pediatric-onset multiple sclerosis–specific domains and items. The final interview phase with 5 youth with pediatric-onset multiple sclerosis and 5 parents comprised a pilot testing of the new PedsQL MS Module. Results: Eighteen domains were derived from the qualitative methods with item content saturation achieved at 100 items based on 40 interviews with 23 youth with pediatric-onset multiple sclerosis aged 10-21 years and 17 parents. The domains derived include general fatigue, sleep/rest fatigue, cognitive functioning, tingling sensations, numbness sensations, physical weakness, pain, speech, balance, fine motor, vision, urination, constipation, bowel incontinence, worry, communication, treatment, and medicines. Conclusions: Qualitative methods involving 23 youth with pediatric-onset multiple sclerosis and 17 parents in the domain and item development process support the content validity for the new PedsQL MS Module. Future plans include a national field test of the PedsQL MS Module scales and items. © The Author(s) 2021.
Author Keywords
health-related quality of life; multiple sclerosis; patient-reported outcomes; pediatrics; PedsQL; qualitative methods; symptoms
Funding details
National Multiple Sclerosis Society
PP-1712-29484
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“The Longitudinal Early-onset Alzheimer’s Disease Study (LEADS): Framework and methodology” (2021) Alzheimer’s and Dementia
The Longitudinal Early-onset Alzheimer’s Disease Study (LEADS): Framework and methodology
(2021) Alzheimer’s and Dementia, .
Apostolova, L.G.a b aa , Aisen, P.c , Eloyan, A.d , Fagan, A.e , Fargo, K.N.f , Foroud, T.b , Gatsonis, C.d , Grinberg, L.T.g h , Jack, C.R., Jr.i , Kramer, J.h , Koeppe, R.j , Kukull, W.A.k , Murray, M.E.l , Nudelman, K.b , Rumbaugh, M.b , Toga, A.m , Vemuri, P.i , Trullinger, A.n , Iaccarino, L.h , Day, G.S.o , Graff-Radford, N.R.o , Honig, L.S.p , Jones, D.T.i q , Masdeu, J.r , Mendez, M.s , Musiek, E.e , Onyike, C.U.t , Rogalski, E.u , Salloway, S.v , Wolk, D.A.w , Wingo, T.S.x , Carrillo, M.C.y , Dickerson, B.C.z , Rabinovici, G.D.h , the LEADS Consortiumaa
a Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine Indianapolis, Indianapolis, IN, United States
b Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States
c Alzheimer’s Therapeutic Research Institute, University of Southern California, San Diego, CA, United States
d Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, RI, United States
e Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
f Charcot-Marie Tooth Research Foundation, Naperville, IL, United States
g Department of Pathology, University of California, San Francisco, CA, United States
h Department of Neurology, University of California, San Francisco, CA, United States
i Department of Radiology, Mayo Clinic, Rochester, MN, United States
j Department of Radiology, University of Michigan, Ann Arbor, MI, United States
k Department of Epidemiology, University of Washington, Seattle, WA, United States
l Department of Neuroscience, Mayo Clinic, Jacksonville, FL, United States
m Laboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Los Angeles, CA, United States
n Indiana Clinical and Translational Sciences Institute, Indiana University School of Medicine Indianapolis, Indianapolis, IN, United States
o Department of Neurology, Mayo Clinic, Jacksonville, FL, United States
p Taub Institute and Department of Neurology, Columbia University Irving Medical Center, New York, NY, United States
q Department of Neurology, Mayo Clinic, Rochester, MN, United States
r Nantz National Alzheimer Center, Houston Methodist and Weill Cornell Medicine, Houston, TX, United States
s Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
t Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
u Department of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer’s Disease, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
v Department of Neurology, Alpert Medical School, Brown University, Providence, RI, United States
w Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
x Department of Neurology and Human Genetics, Emory University School of Medicine, Atlanta, GA, United States
y Medical & Scientific Relations Division, Alzheimer’s Association, Chicago, IL, United States
z Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
aa Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, United States
Abstract
Patients with early-onset Alzheimer’s disease (EOAD) are commonly excluded from large-scale observational and therapeutic studies due to their young age, atypical presentation, or absence of pathogenic mutations. The goals of the Longitudinal EOAD Study (LEADS) are to (1) define the clinical, imaging, and fluid biomarker characteristics of EOAD; (2) develop sensitive cognitive and biomarker measures for future clinical and research use; and (3) establish a trial-ready network. LEADS will follow 400 amyloid beta (Aβ)-positive EOAD, 200 Aβ-negative EOnonAD that meet National Institute on Aging–Alzheimer’s Association (NIA-AA) criteria for mild cognitive impairment (MCI) or AD dementia, and 100 age-matched controls. Participants will undergo clinical and cognitive assessments, magnetic resonance imaging (MRI), [18F]Florbetaben and [18F]Flortaucipir positron emission tomography (PET), lumbar puncture, and blood draw for DNA, RNA, plasma, serum and peripheral blood mononuclear cells, and post-mortem assessment. To develop more effective AD treatments, scientists need to understand the genetic, biological, and clinical processes involved in EOAD. LEADS will develop a public resource that will enable future planning and implementation of EOAD clinical trials. © 2021 the Alzheimer’s Association
Author Keywords
Alzheimer’s disease; early-onset; EOAD; LEADS; YOAD; young onset
Funding details
National Institutes of HealthNIH
Foundation for the National Institutes of HealthFNIH
National Institute on AgingNIA
Mayo Clinic
Alzheimer’s AssociationAALEADS GENETICS‐19‐639372, P30 AG010124, P30 AG010133, P30 AG013854, P30 AG062421, P30 AG062422, P50 AG005146, P50 AG005681, P50 AG008702, P50 AG023501, P50 AG025688, U01 AG016976
Alzheimer’s Drug Discovery FoundationADDF
Novartis
Roche
Biogen
Janssen Pharmaceuticals
American College of RadiologyACR
Rainwater Charitable FoundationRCF
Eisai
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Cataloguing and characterizing interests in typically developing toddlers and toddlers who develop ASD” (2021) Autism Research
Cataloguing and characterizing interests in typically developing toddlers and toddlers who develop ASD
(2021) Autism Research, .
Burrows, C.A.a , Bodfish, J.W.b , Wolff, J.J.c , Vollman, E.P.d , Altschuler, M.R.e , Botteron, K.N.f , Dager, S.R.g , Estes, A.M.h , Hazlett, H.C.i , Pruett, J.R., Jr.f , Schultz, R.T.j , Zwaigenbaum, L.k , Piven, J.i , Elison, J.T.e , the IBIS Networkl
a Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States
b Department of Hearing & Speech Sciences, Department of Psychiatry & Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, United States
c Department of Educational Psychology, University of Minnesota, Minneapolis, MN, United States
d Department of Psychology and Comparative Human Development, University of Chicago, Chicago, IL, United States
e Institute of Child Development, University of Minnesota, Minneapolis, MN, United States
f Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
g Department of Radiology, University of Washington, Seattle, WA, United States
h Center on Human Development and Disability, University of Washington, Seattle, WA, United States
i Department of Psychiatry, University of North Carolina, Chapel Hill, NC, United States
j Children’s Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
k Autism Research Centre, Department of Pediatrics, University of Alberta, Edmonton, Canada
Abstract
Intense interests are common in children with and without autism spectrum disorder (ASD), and little research has characterized aspects of interests that are unique to or shared among children with and without ASD. We aimed to characterize interests in a sample of infants at high-familial-risk (HR) and low-familial-risk (LR) for ASD using a novel interview. Participants included HR siblings who were diagnosed with ASD at 24 months (HR-ASD, n = 56), HR siblings who did not receive an ASD diagnosis at 24 months (HR-Neg, n = 187), and a LR comparison group (n = 109). We developed and collected data with the Intense Interests Inventory at 18- and 24-months of age, a semi-structured interview that measures intensity and peculiarity of interests in toddlers and preschool-aged children. Intensity of interests differed by familial risk at 24 months, with HR-ASD and HR-Neg groups demonstrating equivalent intensity of interests that were higher than the LR group. By contrast, peculiarity of interest differed by ASD diagnosis, with the HR-ASD group showing more peculiar interests than the HR-Neg and LR groups at 24 months. At 18 months the HR-ASD group had more peculiar interests than the LR group, though no differences emerged in intensity of interests. This measure may be useful in identifying clinically-relevant features of interests in young children with ASD. We also replicated previous findings of males showing more intense interests at 18 months in our non-ASD sample. These results reveal new information about the nature of interests and preoccupations in the early autism phenotype. Lay summary: Intense interests are common in young children with autism and their family members. Intense interests are also prevalent among typically-developing children, and especially boys. Here we catalog interests and features of these interests in a large sample of toddlers enriched for autism risk. Children who had family members with autism had more intense interests, and those who developed autism themselves had more unusual interests at 24 months. These results highlight the importance of different aspects of interest in autism. © 2021 International Society for Autism Research and Wiley Periodicals LLC.
Author Keywords
attention; autism spectrum disorder; intense interests; problem behavior; restricted interests; toddlers
Funding details
National Institutes of HealthNIHHD079124, HD86984, K12‐HD055887, R01 HD055741
Autism SpeaksAS6020
Simons FoundationSF140209, MH118362‐02S1, R01 MH118362
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“NF1 mutation drives neuronal activity-dependent initiation of optic glioma” (2021) Nature
NF1 mutation drives neuronal activity-dependent initiation of optic glioma
(2021) Nature, .
Pan, Y.a , Hysinger, J.D.a , Barron, T.a , Schindler, N.F.a , Cobb, O.b , Guo, X.b , Yalçın, B.a , Anastasaki, C.b , Mulinyawe, S.B.a , Ponnuswami, A.a , Scheaffer, S.b , Ma, Y.b , Chang, K.-C.c , Xia, X.c , Toonen, J.A.b , Lennon, J.J.a , Gibson, E.M.a d , Huguenard, J.R.a , Liau, L.M.e , Goldberg, J.L.c , Monje, M.a d f g h , Gutmann, D.H.b
a Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, United States
b Department of Neurology, Washington University School of Medicine, St Louis, MO, United States
c Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Stanford, CA, United States
d Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States
e Department of Neurosurgery, University of California Los Angeles, Los Angeles, CA, United States
f Department of Pediatrics, Stanford University, Stanford, CA, United States
g Department of Neurosurgery, Stanford University, Stanford, CA, United States
h Department of Pathology, Stanford University, Stanford, CA, United States
Abstract
Neurons have recently emerged as essential cellular constituents of the tumour microenvironment, and their activity has been shown to increase the growth of a diverse number of solid tumours1. Although the role of neurons in tumour progression has previously been demonstrated2, the importance of neuronal activity to tumour initiation is less clear—particularly in the setting of cancer predisposition syndromes. Fifteen per cent of individuals with the neurofibromatosis 1 (NF1) cancer predisposition syndrome (in which tumours arise in close association with nerves) develop low-grade neoplasms of the optic pathway (known as optic pathway gliomas (OPGs)) during early childhood3,4, raising the possibility that postnatal light-induced activity of the optic nerve drives tumour initiation. Here we use an authenticated mouse model of OPG driven by mutations in the neurofibromatosis 1 tumour suppressor gene (Nf1)5 to demonstrate that stimulation of optic nerve activity increases optic glioma growth, and that decreasing visual experience via light deprivation prevents tumour formation and maintenance. We show that the initiation of Nf1-driven OPGs (Nf1-OPGs) depends on visual experience during a developmental period in which Nf1-mutant mice are susceptible to tumorigenesis. Germline Nf1 mutation in retinal neurons results in aberrantly increased shedding of neuroligin 3 (NLGN3) within the optic nerve in response to retinal neuronal activity. Moreover, genetic Nlgn3 loss or pharmacological inhibition of NLGN3 shedding blocks the formation and progression of Nf1-OPGs. Collectively, our studies establish an obligate role for neuronal activity in the development of some types of brain tumours, elucidate a therapeutic strategy to reduce OPG incidence or mitigate tumour progression, and underscore the role of Nf1mutation-mediated dysregulation of neuronal signalling pathways in mouse models of the NF1 cancer predisposition syndrome. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
Funding details
National Institutes of HealthNIHDP1NS111132
U.S. Department of DefenseDODW81XWH-15-1-0131, W81XWH-19-1-0260
National Eye InstituteNEIF32EY029137, P30EY026877
National Cancer InstituteNCIP50CA165962
National Institute of Neurological Disorders and StrokeNINDSR01NS092597, R35NS07211
Alex’s Lemonade Stand Foundation for Childhood CancerALSF
Research to Prevent BlindnessRPB
Ian’s Friends FoundationIFF
Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation
Stanford Maternal and Child Health Research InstituteMCHRI
Gilbert Family FoundationGFF
Cancer Research UKCRUK
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Cognitive Recovery After Stroke: A Meta-analysis and Metaregression of Intervention and Cohort Studies” (2021) Neurorehabilitation and Neural Repair
Cognitive Recovery After Stroke: A Meta-analysis and Metaregression of Intervention and Cohort Studies
(2021) Neurorehabilitation and Neural Repair, .
Saa, J.P.a b , Tse, T.a , Baum, C.M.c d , Cumming, T.b , Josman, N.e , Rose, M.a , O’Keefe, S.a , Sewell, K.a b , Nguyen, V.a , Carey, L.M.a b
a La Trobe University, Melbourne, VIC, Australia
b University of Melbourne, Melbourne, Australia
c Washington University, Saint Louis, MO, United States
d Washington University School of Medicine, St Louis, MO, United States
e University of Haifa, Haifa, Israel
Abstract
Background: Cognition affects poststroke recovery, but meta-analyses of cognition have not yet provided a comparison of observational and intervention evidence. Objective: To describe the trajectory of poststroke cognition and the factors that moderate it across intervention and observational cohorts. Methods: Six databases were searched up to January 2020. Studies describing quantitative changes in cognition in adults poststroke were included. Interventions were classified into pharmacological, therapist-led, nonroutine/alternative, and usual care. Summary estimates were compared via hierarchical mixed-effects models. Age, recovery stage, stroke etiology, cognitive domain targeted in studies, and intervention types were investigated as moderators of cognition. Recovery stage and intervention were further analyzed in a multiplicative metaregression model. Results: A total of 43 intervention trials and 79 observation cohorts involving 28 222 stroke participants were included. Heterogeneity was significant (τ2 = 0.09; CI = 0.01-0.21, P <.001) with no evidence of publication bias. Cognitive recovery was greater in intervention trials (g = 0.47; CI = 0.37-0.58) than observational cohorts (g = 0.28; CI = 0.20-0.36) across all moderators analyzed. Nonroutine/alternative and pharmacological trials achieved the best overall results (g = 0.57, CI = 0.42-0.73, and g = 0.52, CI = 0.30-0.74, respectively), followed by therapist-led (g = 0.46; CI = 0.17-0.74), and usual care (g = 0.28; CI = 0.11-0.45) interventions. Medium recovery effects (ie, g ≥ 0.5) were observed in examining first-ever stroke, executive function, visuo-perceptual, consciousness, and psychomotor skills, 61 to 180 days poststroke, in participants aged 65 to 70 years. Conclusion: Cognitive recovery is possible using different controlled interventions in all recovery stages, with smaller benefits ≥2 years poststroke. Longer-term studies are needed to determine the role of nonroutine/alternative therapies and the association between cognitive recovery and performance in everyday activities. © The Author(s) 2021.
Author Keywords
cognition; executive function; longitudinal studies; meta-analysis; rehabilitation; stroke
Funding details
James S. McDonnell FoundationJSMF220020413
National Health and Medical Research CouncilNHMRC1077898, 1113352, 1153236, 2004443
Commonwealth Scientific and Industrial Research OrganisationCSIRO
La Trobe University
Document Type: Review
Publication Stage: Article in Press
Source: Scopus
“Hemispheric CSF volume ratio quantifies progression and severity of cerebral edema after acute hemispheric stroke” (2021) Journal of Cerebral Blood Flow and Metabolism
Hemispheric CSF volume ratio quantifies progression and severity of cerebral edema after acute hemispheric stroke
(2021) Journal of Cerebral Blood Flow and Metabolism, .
Dhar, R.a , Hamzehloo, A.a , Kumar, A.a , Chen, Y.a , He, J.b , Heitsch, L.a c , Slowik, A.d , Strbian, D.e , Lee, J.-M.a f g
a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, United States
d Department of Neurology, Jagiellonian University Medical College, Krakow, Poland
e Department of Neurology, Helsinki University Hospital, Helsinki, Finland
f Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
g Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, United States
Abstract
As swelling occurs, CSF is preferentially displaced from the ischemic hemisphere. The ratio of CSF volume in the stroke-affected hemisphere to that in the contralateral hemisphere may quantify the progression of cerebral edema. We automatically segmented CSF from 1,875 routine CTs performed within 96 hours of stroke onset in 924 participants of a stroke cohort study. In 737 subjects with follow-up imaging beyond 24-hours, edema severity was classified as affecting less than one-third of the hemisphere (CED-1), large hemispheric infarction (LHI, over one-third the hemisphere), without midline shift (CED-2) or with midline shift (CED-3). Malignant edema was LHI resulting in deterioration, requiring osmotic therapy, surgery, or resulting in death. Hemispheric CSF ratio was lower on baseline CT in those with LHI (0.91 vs. 0.97, p < 0.0001) and decreased more rapidly in those with LHI who developed midline shift (0.01 per hour for CED-3 vs. 0.004/hour CED-2). The ratio at 24-hours was lower in those with midline shift (0.41, IQR 0.30–0.57 vs. 0.66, 0.56–0.81 for CED-2). A ratio below 0.50 provided 90% sensitivity, 82% specificity for predicting malignant edema among those with LHI (AUC 0.91, 0.85–0.96). This suggests that the hemispheric CSF ratio may provide an accessible early biomarker of edema severity. © The Author(s) 2021.
Author Keywords
brain edema; cerebrospinal fluid; CT; imaging; Stroke
Funding details
National Institutes of HealthNIHK23NS099440, K23NS099487, R01NS085419, U24NS107230
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Mechanisms of Broad-Band UVB Irradiation‒Induced Itch in Mice” (2021) Journal of Investigative Dermatology
Mechanisms of Broad-Band UVB Irradiation‒Induced Itch in Mice
(2021) Journal of Investigative Dermatology, .
Cao, L.a b , Yue, X.a b , Zhao, Y.a b , Du, L.a b , Xie, Z.a b , Yuan, Y.a b , Zhang, S.c , Li, F.c , Feng, J.a b , Hu, H.a b
a Washington University School of Medicine in St. Louis, St. Louis, MO, United States
b Department of Anesthesiology, Center for the Study of Itch & Sensory Disorders, Washington University School of Medicine in St. Louis, St. Louis, MO, United States
c Department of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang, China
Abstract
Although sunburn can produce severe uncontrollable itching, the underlying mechanisms of UV irradiation‒induced itch are poorly understood because of a lack of experimental animal models of sunburn itch. In this study, we established a sunburn-related mouse model and found that broad-band UVB irradiation elicited scratching but not wiping behavior in mice. Using a combination of live-cell calcium ion imaging and quantitative RT-PCR on dorsal root ganglion neurons, H&E staining, immunofluorescence staining of skin preparations, and behavioral testing, in combination with genetic and pharmacological approaches, we showed that TRPV1-positive dorsal root ganglion neurons but not mast cells are involved in broad-band UVB irradiation‒induced itch. Moreover, both genetic and pharmacological inhibition of TRPV1 function significantly alleviated the broad-band UVB irradiation‒induced itch response. Collectively, our results suggest that broad-band UVB irradiation evokes itch sensation in mice by promoting TRPV1 channel function in dorsal root ganglion neurons and provide potential therapeutic targets for sunburn-related itch. © 2021 The Authors
Funding details
National Institutes of HealthNIHR01AA027065, R01AR077183, R01DK103901
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Cognitive functioning of older adults prior to hematopoietic stem cell transplantation” (2021) Bone Marrow Transplantation
Cognitive functioning of older adults prior to hematopoietic stem cell transplantation
(2021) Bone Marrow Transplantation, .
Lacy, M.a , Fong, M.b , Bolton, C.c , Maranzano, M.d , Bishop, M.a , Artz, A.e
a University of Chicago Medical Center, Chicago, United States
b Washington University in St. Louis, St. Louis, MO, United States
c Vanderbilt University, Nashville, TN, United States
d University of California, Los Angeles, CA, United States
e City of Hope National Medicine Center, Duarte, CA, United States
Abstract
Hematopoietic cell transplantation is increasingly used in older adults with hematological malignancies. Younger adult patients who undergo HCT have shown to commonly present with cognitive impairment and depression prior to transplant; however, little research has been done to understand the cognitive and emotional functioning of older adults undergoing HCT. This study aimed to investigate the rate of cognitive impairment in a retrospective sample of older adult HCT candidates prior to transplant using a comprehensive battery. Ninety-three patients over the age of 60 completed a neuropsychology test battery that assessed standard domains of cognitive and emotional functioning. Impairment was defined as z-scores = < −1.5 on at least two tests or a z score = < −2.0 on at least one test. Results indicated that over 68% of patients were impaired with nearly a third of the sample showing impairment in verbal learning and memory and approximately one fifth showing impairments in aspects of executive function, processing speed, and visual learning. Ten percent of the patients endorsed symptoms indicative of a clinical level of depression. Medical comorbidities nor depression predicted cognitive impairment. These findings suggest that older adults candidates for HCT are at risk for cognitive impairment prior to transplant and thus cognition should be a consideration when developing treatment plans. © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation” (2021) Genetics in Medicine
Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation
(2021) Genetics in Medicine, . Cited 1 time.
Legius, E.a , Messiaen, L.b , Wolkenstein, P.c , Pancza, P.d , Avery, R.A.e , Berman, Y.f , Blakeley, J.g , Babovic-Vuksanovic, D.h , Cunha, K.S.i , Ferner, R.j , Fisher, M.J.k , Friedman, J.M.l , Gutmann, D.H.m , Kehrer-Sawatzki, H.n , Korf, B.R.b , Mautner, V.-F.o , Peltonen, S.p q , Rauen, K.A.r , Riccardi, V.s , Schorry, E.t , Stemmer-Rachamimov, A.u , Stevenson, D.A.v , Tadini, G.w , Ullrich, N.J.x , Viskochil, D.y , Wimmer, K.z , Yohay, K.aa , Gomes, A.b , Jordan, J.T.ad , Mautner, V.o , Merker, V.L.ad , Smith, M.J.ac , Stevenson, D.v , Anten, M.ae , Aylsworth, A.af , Baralle, D.ag , Barbarot, S.ah , Barker, F., IIai , Ben-Shachar, S.aj , Bergner, A.ak , Bessis, D.al , Blanco, I.am , Cassiman, C.an , Ciavarelli, P.ao , Clementi, M.ap , Frébourg, T.aq , Giovannini, M.ar , Halliday, D.as , Hammond, C.at , Hanemann, C.O.au , Hanson, H.av , Heiberg, A.aw , Joly, P.ax , Kalamarides, M.ay , Karajannis, M.az , Kroshinsky, D.ba , Larralde, M.bb , Lázaro, C.bc , Le, L.bd , Link, M.be , Listernick, R.bf , MacCollin, M.bg , Mallucci, C.bh , Moertel, C.bi , Mueller, A.bj , Ngeow, J.bk , Oostenbrink, R.bl , Packer, R.bm , Papi, L.bn , Parry, A.bo , Peltonen, J.bp , Pichard, D.bq , Poppe, B.br , Rezende, N.bs , Rodrigues, L.O.bt , Rosser, T.bt , Ruggieri, M.bu , Serra, E.bv , Steinke-Lange, V.bw , Stivaros, S.M.bx , Taylor, A.by , Toelen, J.bz , Tonsgard, J.ca , Trevisson, E.ap , Upadhyaya, M.cb , Varan, A.cc , Wilson, M.cd , Wu, H.ce , Zadeh, G.cf , Huson, S.M.ab , Evans, D.G.ac , Plotkin, S.R.ad , International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC)cg
a Department of Human Genetics, KU Leuven and University Hospital, Leuven, Belgium
b Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, United States
c Assistance Publique-Hôpital Paris (AP-HP), Hôpital Henri-Mondor, UPEC, Service de Dermatologie, Créteil, France
d Children’s Tumor Foundation, New York, NY, United States
e Division of Ophthalmology, The Children’s Hospital of Philadelphia, Philadelphia, PA, United States
f Clinical Genetics, Royal North Shore Hospital, St. Leonards, NSW, Australia and University of Sydney, Sydney, Australia
g Johns Hopkins Comprehensive Neurofibromatosis Center, Baltimore, MD, United States
h Department of Clinical Genomics, Mayo Clinic College of Medicine, Rochester, MN, United States
i Department of Pathology, Universidade Federal Fluminense, Niteroi, Brazil
j Neurology, Guy’s and St. Thomas’ Hospital and NHS Trust, London, United Kingdom
k Division of Oncology, The Children’s Hospital of Philadelphia, Philadelphia, PA, United States
l Medical Genetics, University of British Columbia, Vancouver, BC, Canada
m Neurology, Washington University, St. Louis, MO, United States
n Institute of Human Genetics, University of Ulm, Ulm, Germany
o Neurology, University Hospital of Hamburg-Eppendorf, Hamburg, Germany
p Dermatology, University of Turku and Turku University Hospital, Turku, Finland
q Department of Dermatology and Venereology, University of Gothenburg, Gothenburg, Sweden
r Pediatrics, University of California Davis, Sacramento, CA, United States
s The Neurofibromatosis Institute, La Crescenta, CA, United States
t Medical Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States
u Neuropathology, Massachusetts General Hospital, Boston, MA, United States
v Medical Genetics, Stanford University, Stanford, CA, United States
w Pediatric Dermatology, University of Milan, Milan, Italy
x Department of Neurology, Boston Children’s Hospital, Boston, MA, United States
y Medical Genetics, University of Utah, Salt Lake City, UT, United States
z Institute of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria
aa NYU Langone Health, New York, NY, United States
ab Clinical Genetics, (Formerly) Manchester Center for Genomic Medicine, Manchester University Hospitals, NHS Foundation Trust, Manchester, United Kingdom
ac Department of Genomic Medicine, St Mary’s Hospital, Manchester Academic Health Sciences Centre (MAHSC), Division of Evolution and Genomic Science, University of Manchester, Manchester, United Kingdom
ad Department of Neurology and Cancer Center, Massachusetts General Hospital, Boston, MA, United States
ae Department of Neurology, Maastricht University Medical Center, Maastricht, Netherlands
af Department of Genetics, University of North Carolina, Chapel Hill, NC, United States
ag Department of Human Development and Health, University of Southampton, Southampton, United Kingdom
ah Centre Hospitalier Universitaire de Nantes, Nantes, France
ai Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, United States
aj Clalit Research Institute, & Schneider Children’s Medical Center, Ramat-Gan, Israel
ak Department of Genetics and Development, Columbia University Medical Center, New York, NY, United States
al Department of Dermatology, Centre Hospitalier Universitaire de Montpellier, Montpellier, France
am Department of Clinical Genetics, Hospital Universitari Germans Trias I Pujol, Badalona, Spain
an Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium
ao Department of Neurosurgery, Hospital de Clinicas Gral San Martin, San Martin, Argentina
ap Department of Clinical Genetics, University of Padova, Padova, Italy
aq Department of Genetics, University Hospital Rouen, Rouen, France
ar Department of Head and Neck Surgery, David Geffen School of Medicine, University of California–Los Angeles, Los Angeles, CA, United States
as Department of Clinical Genetics, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
at Department of Ophthalmology, King’s College London, London, United Kingdom
au Institute of Translational and Stratified Medicine, Peninsula Medical School, University of Plymouth, Plymouth, United Kingdom
av Department of Genetics, St George’s University Hospitals, London, United Kingdom
aw Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
ax Department of Dermatology, University Hospital Rouen, Rouen, France
ay Department of Neurosurgery, Hôpital Pitié Salpêtrière, Paris, France
az Department of Pediatrics and Otolaryngology, Memorial Sloan Kettering Cancer Center, New York, NY, United States
ba Department of Dermatology, Massachusetts General Hospital, Boston, MA, United States
bb Department of Dermatology, Hospital Aleman, Buenos Aires, Argentina
bc Institut Català d’Oncologia (ICO-IDIBELL-CIBERONC), Hospitalet de Llobregat, Barcelona, Spain
bd Department of Dermatology, University of Texas, Southwestern, Dallas, TX, United States
be Department of Neurosurgery and Otolaryngology, Mayo Clinic, Rochester, MN, United States
bf Department of Pediatrics, Ann and Robert H Lurie Children’s Hospital of Chicago, Chicago, IL, United States
bg Bend, OR, United States
bh Department of Neurosurgery, Alder Hey Children’s Hospital NHS, Liverpool, United Kingdom
bi Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States
bj Cancer Genetics, Massachusetts General Hospital, Boston, MA, United States
bk Lee Kong Chian School of medicine, Nanyang Technological University, Singapore and Cancer Genetics Service, National Cancer Center, Singapore, Singapore
bl Department of Pediatrics, Erasmus University Medical Center, Rotterdam, Netherlands
bm The Brain Tumor Institute, Gilbert Family Neurofibromatosis Institute, Children’s National Medical Center, Washington, DC, United States
bn Department of Experimental and Clinical Biomedical Science “Mario Serio”, University of Florence, Florence, Italy
bo Department of Neurology, John Radcliff Hospital, Oxford, United Kingdom
bp Institute of Biomedicine, University of Turku and Turku University Hospital, Turku, Finland
bq National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, United States
br Department of Medical Genetics, University Hospital Ghent, Ghent, Belgium
bs School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil
bt Department of Neurology, Children’s Hospital Los Angeles, Los Angeles, CA, United States
bu Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
bv The Institute for Health Science Research Germans Trias i Pujol (IGTP), Barcelona, Spain
bw Center of Medical Genetics, Munich, Germany
bx Division of Informatics, Imaging and Data Sciences, University of Manchester, Manchester, United Kingdom
by Clinical Genetics Department, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
bz Department of Pediatrics, University Hospital Leuven, Leuven, Belgium
ca Department of Pediatrics and Neurology, University of Chicago Medicine, Chicago, IL, United States
cb Institute of Cancer Genetics, Cardiff University, Cardiff, United Kingdom
cc Department of Pediatric Oncology, Hacettepe University, Ankara, Turkey
cd Department of Clinical Genetics, Children’s Hospital Westmead, Sydney, Australia
ce Shanghai Ninth People’s Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shangai, China
cf Princess Margaret Cancer Centre, Toronto Western Hospital, Toronto, ON, Canada
Abstract
Purpose: By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). Methods: We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. Results: We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. Conclusion: The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS. [Figure not available: see fulltext.] © 2021, The Author(s).
Funding details
IS-BRC-1215-20007
Children’s Tumor FoundationCTF
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Intracochlear Electrocochleography and Speech Perception Scores in Cochlear Implant Recipients” (2021) Laryngoscope
Intracochlear Electrocochleography and Speech Perception Scores in Cochlear Implant Recipients
(2021) Laryngoscope, .
Valenzuela, C.V.a , Lichtenhan, J.T.a , Lefler, S.M.a , Koka, K.b , Buchman, C.A.a , Ortmann, A.J.a
a Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States
b Department of Research and Technology, Advanced Bionics Corporation, Valencia, CA, United States
Abstract
Objectives/Hypothesis: Previous studies have demonstrated that electrocochleography (ECochG) measurements made at the round window prior to cochlear implant (CI) electrode insertion can account for 47% of the variability in 6-month speech perception scores. Recent advances have made it possible to use the apical CI electrode to record intracochlear responses to acoustic stimuli. Study objectives were to determine 1) the relationship between intracochlear ECochG response amplitudes and 6-month speech perception scores and 2) to determine the relationship between behavioral auditory thresholds and ECochG threshold estimates. The hypothesis was that intracochlear ECochG response amplitudes made immediately after electrode insertion would be larger than historical controls (at the extracochlear site) and explain more variability in speech perception scores. Study Design: Prospective case series. Methods: Twenty-two adult CI recipients with varying degrees of low-frequency hearing had intracochlear ECochG measurements made immediately after CI electrode insertion using 110 dB SPL tone bursts. Tone bursts were centered at five octave-spaced frequencies between 125 and 2,000 Hz. Results: There was no association between intracochlear ECochG response amplitudes and speech perception scores. But, the data suggest a mild to moderate relationship between preoperative behavioral audiometric testing and intraoperative ECochG threshold estimates. Conclusion: Performing intracochlear ECochG is highly feasible and results in larger response amplitudes, but performing ECochG before, rather than after, CI insertion may provide a more accurate assessment of a patient’s speech perception potential. Level of Evidence: 4 Laryngoscope, 2021. © 2021 The American Laryngological, Rhinological and Otological Society, Inc.
Author Keywords
cochlear implant performance; Electrocochleography; intracochlear
Funding details
National Institutes of HealthNIHT32DC000022, UL1 TR002345
National Institute on Deafness and Other Communication DisordersNIDCD
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Venovenous versus venoarterial extracorporeal membrane oxygenation among infants with hypoxic-ischemic encephalopathy: is there a difference in outcome?” (2021) Journal of Perinatology
Venovenous versus venoarterial extracorporeal membrane oxygenation among infants with hypoxic-ischemic encephalopathy: is there a difference in outcome?
(2021) Journal of Perinatology, .
Agarwal, P.a , Natarajan, G.a , Sullivan, K.b , Rao, R.c , Rintoul, N.d , Zaniletti, I.e , Keene, S.f , Mietzsch, U.g , Massaro, A.N.h , Billimoria, Z.g , Dirnberger, D.i , Hamrick, S.f , Seabrook, R.B.j , Weems, M.F.k , Cleary, J.P.l , Gray, B.W.m , DiGeronimo, R.g , Piazza, A.n , Sysyn, G.o , Coghill, C.p , Black, A.p , Dhanireddy, R.q , Hansen, A.r , Hossain, T.r , Murthy, K.s , Falciglia, G.s , Haberman, B.t , Nathan, A.t , Nelson, K.t , Kingma, P.t , Riddle, S.t , Merhar, S.t , Kaplan, H.t , Reber, K.u , Savani, R.v , Brion, L.v , Ali, N.v , Grover, T.w , Natarajan, G.x , Nedrelow, J.y , Chi, A.y , Johnson, Y.y , Suresh, G.z , Engle, W.aa , Simpson, L.aa , Sokol, G.aa , Pallotto, E.ab , Lyle, R.ac , Rogers, B.ac , Chin, S.ad , Chapman, R.ad , Limjoco, J.ae , Haack, L.ae , Durand, D.af , Asselin, J.af , D’Harlingue, A.af , Joe, P.af , Evans, J.ag , Padula, M.ag , Munson, D.ag , Touch, S.ah , Yanowitz, T.ai , Brozanski, B.aj , Rao, R.aj , McKay, V.ak , Speziale, M.al , Lane, B.al , Moyer, L.al , Short, B.am , Soghier, L.am , Sullivan, K.an , Ling, C.Y.ao , Patel, S.ao , Uhing, M.ap , Datta, A.ap , Birge, N.aq , Wadhawan, R.ar , Jacobsen-Misbe, E.as , DiGeronimo, R.as , Billimoria, Z.as , Lee, K.-S.at , Mikhael, M.au , Ahmad, I.au , for the Children’s Hospital Neonatal Consortium (CHNC) ECMO and HIE focus groupsav
a Department of Pediatrics, Children’s Hospital of Michigan/Central Michigan University, Detroit, MI, United States
b Department of Pediatrics, AI duPont Hospital for Children/Thomas Jefferson University, Wilmington, DE, United States
c Department of Pediatrics, Washington University in St. Louis, St Louis, MO, United States
d Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
e Children’s Hospital Association, Lenexa, KS, United States
f Department of Pediatrics, Children’s Healthcare of Atlanta and Emory University, Atlanta, GA, United States
g Department of Pediatrics, Seattle Children’s Hospital/University of Washington, Seattle, WA, United States
h Department of Pediatrics, The George Washington University School of Medicine and Children’s National Hospital, Washington, DC, United States
i Department of Pediatrics, AI duPont Hospital for Children, Wilmington, DE, United States
j Department of Pediatrics, Nationwide Children’s Hospital and The Ohio State University College of Medicine, Columbus, OH, United States
k Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, TN, United States
l Department of Pediatrics, Children’s Hospital of Orange County, Orange, CA, United States
m Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, United States
n Children’s Healthcare of Atlanta, Atlanta, GA, United States
o Children’s Healthcare of Atlanta at Scottish Rite, Atlanta, GA, United States
p Children’s Hospital of Alabama, Birmingham, AL, United States
q Le Bonheur Children’s Hospital, Memphis, TN, United States
r Children’s Hospital Boston, Boston, MA, United States
s Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, United States
t Cincinnati Children’s Hospital, Cincinnati, OH, United States
u Nationwide Children’s Hospital, Columbus, OH, United States
v Children’s Medical Center, Dallas, TX, United States
w Children’s Hospital Colorado, Aurora, CO, United States
x Children’s Hospital of Michigan, Detroit, MI, United States
y Cook Children’s Health Care System, Fort Worth, TX, United States
z Texas Children’s Hospital, Houston, TX, United States
aa Riley Children’s Hospital, Indianapolis, IN, United States
ab Children’s Mercy Hospitals & Clinics, Kansas City, MO, United States
ac Arkansas Children’s Hospital, Little Rock, AR, United States
ad Children’s Hospital Los Angeles, Los Angeles, CA, United States
ae American Family Children’s Hospital, Madison, WI, United States
af Children’s Hospital & Research Center Oakland, Oakland, CA, United States
ag The Children’s Hospital of Philadelphia, Philadelphia, PA, United States
ah St. Christopher’s Hospital for Children, Philadelphia, PA, United States
ai Children’s Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States
aj St. Louis Children’s Hospital, St Louis, MO, United States
ak All Children’s Hospital, St. Petersburg, FL, United States
al Rady Children’s Hospital, San Diego, CA, United States
am Children’s National Medical Center, Washington, DC, United States
an AI DuPont Hospital for Children, Wilmington, DE, United States
ao Primary Children’s Medical Center, Salt Lake City, UT, United States
ap Children’s Hospital of Wisconsin, Milwaukee, WI, United States
aq Children’s Hospital & Medical Center, Omaha, NE, United States
ar Florida Hospital for Children, Florida, United States
as Seattle Children’s Hospital, Seattle, WA, United States
at Hospital for Sick Children, Toronto, ON, Canada
au Children’s Hospital Orange County, Los Angeles, CA, United States
Abstract
Objective: Our hypothesis was that among infants with hypoxic-ischemic encephalopathy (HIE), venoarterial (VA), compared to venovenous (VV), extracorporeal membrane oxygenation (ECMO) is associated with an increased risk of mortality or intracranial hemorrhage (ICH). Design/methods: Retrospective cohort analysis of infants in the Children’s Hospitals Neonatal Database from 2010 to 2016 with moderate or severe HIE, gestational age ≥36 weeks, and ECMO initiation <7 days of age. The primary outcome was mortality or ICH. Results: Severe HIE was more common in the VA ECMO group (n = 57), compared to the VV ECMO group (n = 53) (47.4% vs. 26.4%, P = 0.02). VA ECMO was associated with a significantly higher risk of death or ICH [57.9% vs. 34.0%, aOR 2.39 (1.08–5.28)] and mortality [31.6% vs. 11.3%, aOR 3.06 (1.08–8.68)], after adjusting for HIE severity. Conclusions: In HIE, VA ECMO was associated with a higher incidence of mortality or ICH. VV ECMO may be beneficial in this population. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Randomized clinical trial investigating the effect of consistent, developmentally-appropriate, and evidence-based multisensory exposures in the NICU” (2021) Journal of Perinatology
Randomized clinical trial investigating the effect of consistent, developmentally-appropriate, and evidence-based multisensory exposures in the NICU
(2021) Journal of Perinatology, .
Pineda, R.a b c d , Smith, J.e , Roussin, J.f , Wallendorf, M.g , Kellner, P.a , Colditz, G.h
a Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, CA, United States
b Department of Pediatrics, Keck School of Medicine, Los Angeles, CA, United States
c Gehr Family Center for Health Systems Science and Innovation, University of Southern California, Los Angeles, CA, United States
d Program in Occupational Therapy, Washington University, St. Louis, MO, United States
e Department of Quality, Safety, and Practice Excellence, St. Louis Children’s Hospital, St. Louis, MO, United States
f Department of Radiation Oncology, Washington University, St. Louis, MO, United States
g Department of Biostatistics, Washington University, St. Louis, MO, United States
h Department of Surgery, Washington University, St. Louis, MO, United States
Abstract
Objective: Evaluate the effect of a manualized multisensory program, applied across NICU hospitalization, on infant and parent outcomes. Study design: Seventy parent-infant dyads (born ≤32 weeks gestation) in a Level IV NICU were randomized at birth to the multisensory program or standard-of-care. Parents in the multisensory group administered prespecified amounts of age-appropriate, evidence-based sensory interventions to their infants each day during NICU hospitalization according to the Supporting and Enhancing NICU Sensory Experiences (SENSE) program. Results: Infants who received the SENSE program had more lethargy on the NICU Network Neurobehavioral Scale (NNNS) (p = 0.05), even after controlling for medical and social risk (p = 0.043), and had higher Communication scores on the Ages and Stages Questionnaire (p = 0.04) at 1-year corrected age, but this relationship failed to reach significance after controlling for medical and social risk (p = 0.12). Conclusion: The SENSE program shows promise for improving outcomes, but more research with larger sample sizes is needed. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
Funding details
National Institutes of HealthNIH
National Institute of Child Health and Human DevelopmentNICHDP30 HD062171
Gordon and Betty Moore FoundationGBMF
Institute of Clinical and Translational SciencesICTSUL1TR002345
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Brain imaging of cannabinoid type I (CB1) receptors in women with cannabis use disorder and male and female healthy controls” (2021) Addiction Biology
Brain imaging of cannabinoid type I (CB1) receptors in women with cannabis use disorder and male and female healthy controls
(2021) Addiction Biology, .
Spindle, T.R.a , Kuwabara, H.b , Eversole, A.a , Nandi, A.b , Vandrey, R.a , Antoine, D.G.a , Umbricht, A.a , Guarda, A.S.a , Wong, D.F.b c , Weerts, E.M.a
a Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
b Division of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States
c Mallinckrodt Institute of Radiology, Washington University in St Louis, Saint Louis, MO, United States
Abstract
Cannabis effects are predominantly mediated by pharmacological actions on cannabinoid type 1 (CB1) receptors. Prior positron emission tomography (PET) studies in individuals who use cannabis included almost exclusively males. PET studies in females are needed because there are sex differences in cannabis effects, progression to cannabis use disorder (CUD), and withdrawal symptom severity. Females with CUD (N = 10) completed two double-blind cannabis smoking sessions (Session 1: placebo; Session 2: active), and acute cannabis effects were assessed. After Session 2, participants underwent 3 days of monitored cannabis abstinence; mood, craving, and withdrawal symptoms were assessed and a PET scan (radiotracer: [11C]OMAR) followed. [11C]OMAR Distribution volume (VT) from these participants was compared with VT of age/BMI-similar female non-users of cannabis (“healthy controls”; N = 10). VT was also compared between female and male healthy controls (N = 7). Females with CUD displayed significantly lower VT than female healthy controls in specific brain regions (hippocampus, amygdala, cingulate, and insula). Amygdala VT was negatively correlated with mood changes (anger/hostility) during abstinence, but VT was not correlated with other withdrawal symptoms or cannabis effects. Among healthy controls, females had significantly higher VT than males in all brain regions examined. Chronic cannabis use appears to foster downregulation of CB1 receptors in women, as observed previously in men, and there are inherent sex differences in CB1 availability. Future studies should elucidate the time course of CB1 downregulation among females who use cannabis and examine the relation between CB1 availability and cannabis effects among other populations (e.g., infrequent users; medicinal users). © 2021 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.
Author Keywords
cannabis use disorder; PET imaging; sex differences
Funding details
National Institutes of HealthNIHDA000412, MH079017
National Institute on Drug AbuseNIDAR21DA043963, T32DA07209
Klarman Family FoundationKFF
National Center for Advancing Translational SciencesNCATS
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Characteristics and Outcomes among US Patients Hospitalized for Ischemic Stroke before vs during the COVID-19 Pandemic” (2021) JAMA Network Open
Characteristics and Outcomes among US Patients Hospitalized for Ischemic Stroke before vs during the COVID-19 Pandemic
(2021) JAMA Network Open, art. no. 10314, .
De Havenon, A.a g , Ney, J.P.b , Callaghan, B.c , Hohmann, S.d , Shippey, E.d , Yaghi, S.e , Anadani, M.f , Majersik, J.J.a g
a Department of Neurology, University of Utah, 175 N Medical Dr, Salt Lake City, UT 84132, United States
b Department of Neurology, Boston University, Boston, MA, United States
c Department of Neurology, University of Michigan, Ann Arbor, United States
d Research Analytics Vizient, Irving, TX, United States
e Department of Neurology, New York University, New York, United States
f Department of Neurology, Washington University in St Louis, St Louis, MI, United States
g Department of Neurology, University of Utah, 175 N Medical Dr, Salt Lake City, UT 84132, United States
Abstract
Importance: After the emergence of COVID-19, studies reported a decrease in hospitalizations of patients with ischemic stroke (IS), but there are little to no data regarding hospitalizations for the remainder of 2020, including outcome data from a large cohort of patients with IS and comorbid COVID-19. Objective: To assess hospital discharge rates, demographic factors, and outcomes of hospitalization associated with the COVID-19 pandemic among US patients with IS before vs during the COVID-19 pandemic. Design, Setting, and Participants: This retrospective cohort study used data from the Vizient Clinical Data Base on 324013 patients with IS at 478 nonfederal hospitals in 43 US states between January 1, 2019, and December 31, 2020. Patients were eligible if they were admitted to the hospital on a nonelective basis and were not receiving hospice care at the time of admission. A total of 41 166 discharged between January and March 2020 were excluded from the analysis because they had unreliable data on COVID-19 status, leaving 282 847 patients for the study. Exposure: Ischemic stroke and laboratory-confirmed COVID-19. Main Outcomes and Measures: Monthly counts of discharges among patients with IS in 2020. Demographic characteristics and outcomes, including in-hospital death, among patients with IS who were discharged in 2019 (control group) were compared with those of patients with IS with or without comorbid COVID-19 (COVID-19 and non-COVID-19 groups, respectively) who were discharged between April and December 2020. Results: Of the 282 847 patients included in the study, 165 912 (50.7% male; 63.4% White; 26.3% aged ≥80 years) were allocated to the control group; 111 418 of 116 935 patients (95.3%; 51.9% male; 62.8% White; 24.6% aged ≥80 years) were allocated to the non-COVID-19 group and 5517 of 116 935 patients (4.7%; 58.0% male; 42.5% White; 21.3% aged ≥80 years) to the COVID-19 group. A mean (SD) of 13846 (553) discharges per month among patients with IS was reported in 2019. Discharges began decreasing in February 2020, reaching a low of 10846 patients in April 2020 before returning to a prepandemic level of 13639 patients by July 2020. A mean (SD) of 13492 (554) discharges per month was recorded for the remainder of 2020. Black and Hispanic patients accounted for 21.4% and 7.0% of IS discharges in 2019, respectively, but accounted for 27.5% and 16.0% of those discharged with IS and comorbid COVID-19 in 2020. Compared with patients in the control and non-COVID-19 groups, those in the COVID-19 group were less likely to smoke (16.0% vs 17.2% vs 6.4%, respectively) and to have hypertension (73.0% vs 73.1% vs 68.2%) or dyslipidemia (61.2% vs 63.2% vs 56.6%) but were more likely to have diabetes (39.8% vs 40.5% vs 53.0%), obesity (16.2% vs 18.4% vs 24.5%), acute coronary syndrome (8.0% vs 9.2% vs 15.8%), or pulmonary embolus (1.9% vs 2.4% vs 6.8%) and to require intubation (11.3% vs 12.3% vs 37.6%). After adjusting for baseline factors, patients with IS and COVID-19 were more likely to die in the hospital than were patients with IS in 2019 (adjusted odds ratio, 5.17; 95% CI, 4.83-5.53; National Institutes of Health Stroke Scale adjusted odds ratio, 3.57; 95% CI, 3.15-4.05). Conclusions and Relevance: In this cohort study, after the emergence of COVID-19, hospital discharges of patients with IS decreased in the US but returned to prepandemic levels by July 2020. Among patients with IS between April and December 2020, comorbid COVID-19 was relatively common, particularly among Black and Hispanic populations, and morbidity was high.. © 2021 American Medical Association. All rights reserved.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus