Medicine and Health Sciences Commons^™

Transcranial Direct Current Stimulation Combined With Repetitive Transcranial Magnetic Stimulation For Depression: A Randomized Clinical Trial, Dongsheng Zhou, Xingxing Li, Shuochi Wei, Chang Yu, Dongmei Wang, Yuchen Li, Jiaxin Li, Junyao Liu, Shen Li, Wenhao Zhuang, Yanli Li, Ruichenxi Luo, Zhiwang Liu, Jimeng Liu, Yongming Xu, Jialin Fan, Guidong Zhu, Weiqian Xu, Yiping Tang, Raymond Y Cho, Thomas R Kosten, Xiang-Yang Zhang

Staff and Researcher Publications

IMPORTANCE: Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are both recognized as effective treatments for depression when applied individually. However, it is unknown whether rTMS combined with tDCS has better efficacy in the treatment of major depressive disorder (MDD).

OBJECTIVE: To investigate the clinical effectiveness and safety of rTMS, tDCS, tDCS + rTMS, and sham tDCS + sham rTMS after 2 weeks of treatment in patients with MDD.

DESIGN, SETTING, AND PARTICIPANTS: This double-blind, sham-controlled randomized clinical trial was conducted from November 2021 to April 2023 at 3 hospitals in China (Kangning Hospital affiliated with Ningbo …

Transport Of Β-Amyloid From Brain To Eye Causes Retinal Degeneration In Alzheimer’S Disease, Qiuchen Cao, Shige Yang, Xiaowei Wang, Huaiqing Sun, Weijie Chen, Yuliang Wang, Junying Gao, Yanchi Wu, Qiuhua Yang, Xue Chen, Songtao Yuan, Ming Xiao, Maiken Nedergaard, Yuqing Huo, Qinghuai Liu

Faculty, Staff and Students Publications

The eye is closely connected to the brain, providing a unique window to detect pathological changes in the brain. In this study, we discovered β-amyloid (Aβ) deposits along the ocular glymphatic system in patients with Alzheimer's disease (AD) and 5×FAD transgenic mouse model. Interestingly, Aβ from the brain can flow into the eyes along the optic nerve through cerebrospinal fluid (CSF), causing retinal degeneration. Aβ is mainly observed in the optic nerve sheath, the neural axon, and the perivascular space, which might represent the critical steps of the Aβ transportation from the brain to the eyes. Aquaporin-4 facilitates the influx …

Actionable Structural Variant Detection Via Rns-Ngs And Dna-Ngs In Patients With Advanced Non-Small Cell Lung Cancer, Dwight Owen, Daniel Morgensztern, Et Al.

2020-Current year OA Pubs

IMPORTANCE: The National Comprehensive Cancer Network (NCCN) guidelines for non-small cell lung cancer suggest that RNA next-generation sequencing (NGS) may improve the detection of fusions and splicing variants compared with DNA-NGS alone. However, there is limited adoption of RNA-NGS in routine oncology clinical care today.

OBJECTIVE: To analyze clinical evidence from a diverse cohort of patients with advanced lung adenocarcinoma and compare the detection of NCCN-recommended actionable structural variants (aSVs; fusions and splicing variants) via concurrent DNA and RNA-NGS vs DNA-NGS alone.

DESIGN, SETTING, AND PARTICIPANTS: This multisite, retrospective cohort study examined patients sequenced between February 2021 and October 2023 …

Race, Gender, And Faculty Retention In Academic Medicine, Taneisha S Scheuermann, Lauren Clark, Nasrin Sultana, Nathalia Machado, Elena Shergina, Deepika Polineni, Grace H Shih, Robert D Simari, Jo A Wick, Kimber P Richter

2020-Current year OA Pubs

IMPORTANCE: Poor retention may be associated with lack of faculty diversity in academic medicine.

OBJECTIVE: To examine differences in faculty retention by gender, degree type, and race and ethnicity using data from US medical schools.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data from 155 medical schools for 1978 to 2021, which were obtained from the Association of American Medical Colleges. Retention rates were calculated by gender, race and ethnicity, and degree type. Time to attrition was estimated using Kaplan-Meier curves and adjusted Cox proportional hazards models were used to examine the differences in retention by gender and race. …

Multicenter Validation Of An Rna-Based Assay To Predict Anti-Pd-1 Disease Control In Patients With Recurrent Or Metastatic Head And Neck Squamous Cell Carcinoma: The Predapt Study, Kevin C Flanagan, Jessica Ley, Douglas Adkins, Eric J Duncavage, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients. There is a critical clinical need to identify patients who benefit from these antiprogrammed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors.

METHODS: Here, we report findings from a multicenter observational study, PREDicting immunotherapy efficacy from …

Antibacterial And Wound Healing Stimulant Nanofibrous Dressing Consisting Of Soluplus And Soy Protein Isolate Loaded With Mupirocin., Maryam Jahani, Azadeh Asefnejad, Mastafa H Al-Musawi, Ahmed A Mohammed, Basma Talib Al-Sudani, Maha Hameed Al-Bahrani, Nada A Kadhim, Mina Shahriari-Khalaji, Hamideh Valizadeh, Fariborz Sharifianjazi, Morteza Mehrjoo, Ketevan Tavamaishvili, Mohamadreza Tavakoli

Rowan-Virtua School of Translational Biomedical Engineering & Sciences Departmental Research

Severe cutaneous injuries may not heal spontaneously and may necessitate the use of supplementary therapeutic methods. Electrospun nanofibers possess high porosity and specific surface area, which provide the necessary microenvironment for wound healing. Here in, the nanofibers of Soluplus-soy protein isolate (Sol-SPI) containing mupirocin (Mp) were fabricated via electrospinning for wound treatment. The fabricated nanofibers exhibited water absorption capacities of about 300.83 ± 29.72% and water vapor permeability values of about 821.8 ± 49.12 g/m2 day. The Sol/SPI/Mp nanofibers showed an in vitro degradability of 33.73 ± 3.55% after 5 days. The ultimate tensile strength, elastic modulus, and elongation of …

Protein Consumption And Risk Of Cvd Among Us Adults: The Multi-Ethnic Study Of Atherosclerosis (Mesa), Ji Yun Tark, Ruosha Li, Bing Yu, Alexis C Wood, Nikhil S Padhye, Marcia C De Oliveira Otto

Faculty, Staff and Students Publications

BACKGROUND: Although some randomized trials have reported beneficial effects of protein intake on cardiometabolic risk factors, evidence from prospective studies have not supported a strong link between protein intake and cardiovascular disease (CVD) risk. It is also unclear whether diversity in protein intake plays a role in CVD risk.

OBJECTIVE: We investigated prospective associations of (1) protein intake, overall and by food source and (2) diversity of protein sources with risk of CVD, coronary heart disease (CHD), and stroke.

METHODS: In a multi-ethnic cohort of 5879 U.S. adults (45-84 years), who were free of CVD at baseline, protein intake was …

Act With Cf: A Randomized Trial Of Acceptance And Commitment Therapy Vs Supportive Psychotherapy For Adults With Cystic Fibrosis, C. Virginia O'Hayer, Patrick J. Smith, Christopher F. Drescher, Heather Bruschwein, Chelsi N. Nurse, Hallie M. Kushner, Krista Ingle, Michael J. Stephen, Jeffrey B. Hoag

Department of Psychiatry and Human Behavior Faculty Papers

PURPOSE: Psychological distress, including anxiety and depression, is common among adults with CF, associating with poor quality of life, lung function, and healthcare utilization. This 3-year, multi-site, telehealth-delivered randomized trial sought to determine whether Acceptance and Commitment Therapy (ACT with CF) is superior to supportive psychotherapy (SP), in improving psychological functioning for adults with CF.

METHODS: One hundred twenty-four adults with CF and elevated anxiety and/or depressive symptoms were recruited coincident with the first COVID lockdown, from Thomas Jefferson University Hospitals, University of Virginia, Augusta University, Duke University Medical Center, and social media. Participants were randomized to 6 weeks of …

Genetic Alterations In Chromatin Regulatory Genes In Upper Tract Urothelial Carcinoma And Urothelial Bladder Cancer., Shuo Wang, Xuzhi Yan, Weihua Lan, Yapeng Wang, Ze Wang, Dali Tong, Yao Zhang, Qiang Ran, Haoyang Li, Junhao Jin, Haiyang Xiao, Jing Xu, Qian Yan, Dianzheng Zhang, Qiang Ma, Hualiang Xiao, Jun Qin, Luofu Wang, Jun Jiang, Qiuli Liu

PCOM Scholarly Works

PURPOSE: Upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) share histomorphological and therapeutic features but distinct epidemiologic and clinicopathologic characteristics. We examined alterations of chromatin regulatory genes in molecular subtypes, clonal relatedness, and T-cell receptor (TCR) diversity in UTUC and UCB.

MATERIALS AND METHODS: Targeted next-generation sequencing or whole-exome DNA sequencing and TCR sequencing were conducted with 34 UTUC and 49 UCB specimens from 63 patients. Tumors were subtyped based on the expression of CK5 and GATA3. Results of tissue microarray of 78 muscle-invasive bladder cancer (MIBC) samples were used as prognostic factors of different subtypes …

Three-Year Outcomes Following Tavr In Younger (<75 Years) Low-Surgical-Risk Severe Aortic Stenosis Patients., Thomas Modine, Didier Tchétché, Nicolas M Van Mieghem, G Michael Deeb, Stanley J Chetcuti, Steven J Yakubov, Paul Sorajja, Hemal Gada, Mubashir Mumtaz, Basel Ramlawi, Tanvir Bajwa, John Crouch, Paul S Teirstein, Neal S Kleiman, Ayman Iskander, Rodrigo Bagur, Michael W A Chu, Pierre Berthoumieu, Arnaud Sudre, Rik Adrichem, Saki Ito, Jian Huang, Jeffrey J Popma, John K Forrest, Michael J Reardon

Heart and Vascular Articles

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an alternative to surgery in patients with severe aortic stenosis, but data are limited on younger, low-risk patients. This analysis compares outcomes in low-surgical-risk patients agedsurgery.

METHODS: The Evolut Low Risk Trial randomized 1414 low-risk patients to treatment with a supra-annular, self-expanding TAVR or surgery. We compared rates of all-cause mortality or disabling stroke, associated clinical outcomes, and bioprosthetic valve performance at 3 years between TAVR and surgery patients aged < 75 >years.

RESULTS: In patients < 75 >years, 352 were randomized to TAVR and 351 to surgery. Mean age was 69.1±4.0 years (minimum 51 and maximum …

Association Between E-Scooter Temporal Usage Patterns With Injuries Resulting In Admission To A Level One Trauma Center, Kevin C Rix, Andrew E Springer, Katelyn Jetelina, Nalini Ranjit, Catherine C Mcdonald, Douglas J Wiebe, Thomas B Coopwood

Faculty, Staff and Student Publications

Background: As e-scooters have become common modes of transportations in urban environments, riding e-scooters has become a common mechanism of injury. This study examines the relationship between when riders are using these devices (i.e. day of week, and time of the day) and injury incidence based on data from a large U.S. city.

Methods: This study is a retrospective cohort study of patients in the trauma registry at a level one trauma center. Registry data were combined with a publicly available dataset of all e-scooter trips that occurred during the study period. Frequency of injuries and trips were analyzed using …

Roflumilast Cream, 015%, For Atopic Dermatitis In Adults And Children: Integument-1 And Integument-2 Randomized Clinical Trials, Eric L Simpson, Lawrence F Eichenfield, Javier Alonso-Llamazares, Zoe D Draelos, Laura K Ferris, Seth B Forman, Melinda Gooderham, Mercedes E Gonzalez, Adelaide A Hebert, Leon H Kircik, Mark Lomaga, Angela Moore, Kim A Papp, Vimal H Prajapati, Diane Hanna, Scott Snyder, David Krupa, Patrick Burnett, Erin Almaraz, Robert C Higham, David H Chu, David R Berk

Faculty, Staff and Student Publications

Importance: Safe, effective, and well-tolerated topical treatment options available for long-term use in patients with atopic dermatitis (AD) are limited and associated with low adherence rates.

Objective: To evaluate efficacy and safety of once-daily roflumilast cream, 0.15%, vs vehicle cream in patients with AD.

Design, setting, and participants: Two phase 3, randomized, double-blind, vehicle-controlled trials (Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 [INTEGUMENT-1 and INTEGUMENT-2]), included patients from sites in the US, Canada, and Poland. Participants were 6 years or older with mild to moderate AD based on Validated Global Assessment for Atopic …

Relationship Between Mri Brain-Age Heterogeneity, Cognition, Genetics And Alzheimer's Disease Neuropathology, Mathilde Antoniades, Pamela Lamontagne, Tammie Benzinger, Daniel S Marcus, John C Morris, Et Al.

2020-Current year OA Pubs

BACKGROUND: Brain ageing is highly heterogeneous, as it is driven by a variety of normal and neuropathological processes. These processes may differentially affect structural and functional brain ageing across individuals, with more pronounced ageing (older brain age) during midlife being indicative of later development of dementia. Here, we examined whether brain-ageing heterogeneity in unimpaired older adults related to neurodegeneration, different cognitive trajectories, genetic and amyloid-beta (Aβ) profiles, and to predicted progression to Alzheimer's disease (AD).

METHODS: Functional and structural brain age measures were obtained for resting-state functional MRI and structural MRI, respectively, in 3460 cognitively normal individuals across an age …

Effectiveness Of Original Monovalent And Bivalent Covid-19 Vaccines Against Covid-19-Associated Hospitalization And Severe In-Hospital Outcomes Among Adults In The United States, September 2022-August 2023, Jennifer Decuir, Jennie H Kwon, Et Al.

2020-Current year OA Pubs

BACKGROUND: Assessments of COVID-19 vaccine effectiveness are needed to monitor the protection provided by updated vaccines against severe COVID-19. We evaluated the effectiveness of original monovalent and bivalent (ancestral strain and Omicron BA.4/5) COVID-19 vaccination against COVID-19-associated hospitalization and severe in-hospital outcomes.

METHODS: During September 8, 2022 to August 31, 2023, adults aged ≥ 18 years hospitalized with COVID-19-like illness were enrolled at 26 hospitals in 20 US states. Using a test-negative case-control design, we estimated vaccine effectiveness (VE) with multivariable logistic regression adjusted for age, sex, race/ethnicity, admission date, and geographic region.

RESULTS: Among 7028 patients, 2924 (41.6%) were …

A Finite Element Model For Biomechanical Characterization Of Ex Vivo Peripheral Nerve Dysfunction During Stretch, Nicholas C Vasas, Adam M Forrest, Nathaniel A Meyers, Michael B Christensen, Jenny L Pierce, Sidney M Kaufmann, Kimberly B Lanaghen, Randal C Paniello, Julie M Barkmeier-Kraemer, Jonathan P Vande Geest

2020-Current year OA Pubs

Peripheral nerve damage can cause debilitating symptoms ranging from numbness and pain to sensory loss and atrophy. To uncover the underlying mechanisms of peripheral nerve injury, our research aims to develop a relationship between biomechanical peripheral nerve damage and function through finite element modeling. A noncontact, ex vivo electrophysiology chamber, capable of axially stretching explanted nerves while recording electrical signals, was used to investigate peripheral nerve injury. Successive stretch trials were run on eight sciatic nerves (four females and four males) excised from Sprague-Dawley rats. Nerves were stretched until 50% compound action potential (CAP) amplitude reduction was obtained. A constitutive …

Fusobacterium Nucleatum Abundance Is Associated With Cachexia In Colorectal Cancer Patients: The Colocare Study, Mmadili N Ilozumba, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cachexia accounts for about 20% of all cancer-related deaths and indicates poor prognosis. The impact of Fusobacterium nucleatum (Fn), a microbial risk factor for colorectal cancer (CRC), on the development of cachexia in CRC has not been established.

METHODS: We evaluated the association between Fn abundance in pre-surgical stool samples and onset of cachexia at 6 months post-surgery in n = 87 patients with stages I-III CRC in the ColoCare Study.

RESULTS: High fecal Fn abundance compared to negative/low fecal Fn abundance was associated with 4-fold increased risk of cachexia onset at 6 months post-surgery (OR = 4.82, 95% …

Evaluation Of Combat Harmonization For Reducing Across-Tracer Differences In Regional Amyloid Pet Analyses, Braden Yang, Tom Earnest, Sayantan Kumar, Deydeep Kothapalli, Tammie Benzinger, Brian Gordon, Aristeidis Sotiras

2020-Current year OA Pubs

Differences in amyloid positron emission tomography (PET) radiotracer pharmacokinetics and binding properties lead to discrepancies in amyloid-β uptake estimates. Harmonization of tracer-specific biases is crucial for optimal performance of downstream tasks. Here, we investigated the efficacy of ComBat, a data-driven harmonization model, for reducing tracer-specific biases in regional amyloid PET measurements from [

A Site-Wise Reliability Analysis Of The Abcd Diffusion Fractional Anisotropy And Cortical Thickness: Impact Of Scanner Platforms, Yezhi Pan, L Elliot Hong, Ashley Acheson, Paul M Thompson, Neda Jahanshad, Alyssa H Zhu, Jiaao Yu, Chixiang Chen, Tianzhou Ma, Ho-Ling Liu, Jelle Veraart, Els Fieremans, Nicole R Karcher, Peter Kochunov, Shuo Chen

2020-Current year OA Pubs

The Adolescent Brain and Cognitive Development (ABCD) project is the largest study of adolescent brain development. ABCD longitudinally tracks 11,868 participants aged 9-10 years from 21 sites using standardized protocols for multi-site MRI data collection and analysis. While the multi-site and multi-scanner study design enhances the robustness and generalizability of analysis results, it may also introduce nonbiological variances including scanner-related variations, subject motion, and deviations from protocols. ABCD imaging data were collected biennially within a period of ongoing maturation in cortical thickness and integrity of cerebral white matter. These changes can bias the classical test-retest methodologies, such as intraclass correlation …

Can Acetabular Dysplasia Be Measured On Axial Ct? A Measurement For Trauma Surgeons, Ravi R Agrawal, Eric R Barnard, Helena F Barber, Anna N Miller

2020-Current year OA Pubs

BACKGROUND: Acetabular dysplasia has been theorized as a risk factor instability amongst common acetabular fractures, such as posterior wall (PW) fractures. However, common radiographic measurements often cannot be acquired in trauma patients. We evaluated axial computed tomography (CT) scans to identify novel, easily-obtained measurements that correlate with acetabular dysplasia for use in surgical indications and planning.

METHODS: Patients with known acetabular dysplasia undergoing elective periacetabular osteotomy were selected. A different group of patients without pelvic ring or acetabular fractures from an institutional trauma registry were selected as a comparison group. Standard indices of dysplasia were collected, such as center-edge angle …

Iglon5 Frequency In Idiopathic Rem Sleep Behavior Disorder: A Multicenter Study, Ronald Postuma, Jennifer Mcleland, Albert A. Davis, Yo-El S. Ju, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.

METHODS: Participants were enrolled in the North American Prodromal Synucleinopathy cohort with polysomnography-confirmed iRBD, free of parkinsonism and dementia. Plasma samples were systematically screened for the autoantibodies IGLON5, DPPX, LGI1, and CASPR2 using plasma …

A Phase 1 First-In-Human Study Of The Mcl-1 Inhibitor Azd5991 In Patients With Relapsed/Refractory Hematologic Malignancies, Pinkal Desai, Amanda Cashen, Et Al.

2020-Current year OA Pubs

PURPOSE: AZD5991, a human MCL-1 inhibitor, was assessed for safety, tolerability, pharmacokinetics, and antitumor activity as monotherapy and in combination with venetoclax in patients with relapsed or refractory hematologic malignancies.

PATIENTS AND METHODS: In the monotherapy cohort (n = 61), patients with hematologic malignancies received AZD5991 intravenously in escalating doses either once or twice weekly, following intrapatient dose escalation, during a 3-week cycle. In the combination cohort (n = 17), patients with acute myeloid leukemia and myelodysplastic syndrome received escalating doses of AZD5991 and venetoclax during either a 3- or 4-week cycle. Primary objectives were safety and maximum tolerated dose; …

Multiomic Profiling Identifies Predictors Of Survival In African American Patients With Acute Myeloid Leukemia, Andrew Stiff, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

Genomic profiles and prognostic biomarkers in patients with acute myeloid leukemia (AML) from ancestry-diverse populations are underexplored. We analyzed the exomes and transcriptomes of 100 patients with AML with genomically confirmed African ancestry (Black; Alliance) and compared their somatic mutation frequencies with those of 323 self-reported white patients with AML, 55% of whom had genomically confirmed European ancestry (white; BeatAML). Here we find that 73% of 162 gene mutations recurrent in Black patients, including a hitherto unreported PHIP alteration detected in 7% of patients, were found in one white patient or not detected. Black patients with myelodysplasia-related AML were younger …

Posttreatment Surveillance Intensity And Overall Survival In Prostate Cancer Survivors (Aft-30), Ronald C Chen, Ramsankar Basak, Stacie Dusetzina, Deborah S Usinger, Zahed Mohammed, Aaron D Falchook, Jessica R Schumacher, Amanda B Francescatti, Amanda Cuddy, George J Chang, Benjamin D Kozower, Caprice C Greenberg, Anne K Barber, Aaron J Katz

2020-Current year OA Pubs

BACKGROUND: Posttreatment surveillance affects millions of cancer survivors, but empiric data to guide clinical practice are lacking. This study assessed whether the intensity of surveillance testing after radical prostatectomy or radiation therapy for localized prostate cancer is associated with overall survival.

METHODS: Men diagnosed with localized prostate cancer between 2005 and 2010 who underwent radical prostatectomy or radiation therapy at a Commission on Cancer-accredited facility were randomly sampled. Primary data collected from 10 147 patients sampled across 1007 facilities were linked with existing data from the National Cancer Database. Analysis examined whether intensity of surveillance measured as the number of …

Determining The N-Glycan And Collagen/Extracellular Matrix Protein Compositions In A Novel Outcome Cohort Of Prostate Cancer Tissue Microarrays Using Maldi-Msi, Jordan P Hartig, Joseph E Ippolito, Et Al.

2020-Current year OA Pubs

Using matrix-assisted laser desorption/ionization mass spectrometry imaging techniques on a unique cohort of prostate cancer tissues, we highlighted several molecular characteristics of matrix that have potential to act as early predictors of prostate cancer metastasis.

Transmembrane Protein 53 Craniotubular Dysplasia (Omim # 619727): The Skeletal Disease And Consequent Blindness Of This New Disorder, Michael P Whyte, Robert S Weinstein, Paul H Phillips, William H Mcalister, Raghuhr H Ramakrishnaiah, G Bradley Schaefer, Rongsheng Cai, Michele R Hutchison, Shenghui Duan, Gary S Gottesman, Steven Mumm

2020-Current year OA Pubs

Craniotubular dysplasia, Ikegawa type (OMIM #619727) denotes the autosomal recessive skeletal disease identified in 2021 featuring blindness acquired in childhood. Five young members of four Indian families harbored a homozygous indel within TMEM53 (OMIM *619722), the gene that encodes transmembrane protein 53 (TMEM53). When intact, TMEM53 spans the nuclear envelope of osteoprogenitor cells, dampens BMP-SMAD signaling, and thereby slows bone formation. Consequently, defective TMEM53 accelerates osteogenesis. Herein, an American boy is compound heterozygous for a novel deletion and a novel missense mutation within TMEM53. His vision and sensorineural hearing became impaired. Radiographic survey revealed diploic thickening of his skull, broad …

Cohort Expansion And Genotype-Phenotype Analysis Of Rab11a-Associated Neurodevelopmental Disorder, Maria Carla Borroto, Jorge L Granadillo, Et Al.

2020-Current year OA Pubs

BACKGROUND: GTPases of the Rab family are important orchestrators of membrane trafficking, and their dysregulation has been linked to a variety of neuropathologies. In 2017, we established a causal link between RAB11A variants and developmental and epileptic encephalopathy. In this study, we expand the phenotype of RAB11A-associated neurodevelopmental disorder and explore genotype-phenotype correlations.

METHODS: We assessed 16 patients with pathogenic or likely pathogenic RAB11A variants, generally de novo, heterozygous missense variants. One individual had a homozygous nonsense variant, although concomitant with a pathogenic LAMA2 variant, which made their respective contributions to the phenotype difficult to discriminate.

RESULTS: We reinforce the …

Effect Of Surgical Fixation Timing On In-Hospital Mortality And Morbidity Of Distal Femur Fractures, Joseph T Gutbrod, Dustin Stwalley, Anna N Miller

2020-Current year OA Pubs

INTRODUCTION: The literature lacks a large-scale study investigating the effect of surgical fixation timing on early mortality and morbidity outcomes in distal femur fractures. The aims of this study were to determine the effect of fixation timing on in-hospital mortality and morbidity outcomes for operatively treated distal femur fractures retrospectively using large database data.

METHODS: This study is a retrospective analysis using data from the National Trauma Data Bank. Patients were stratified into a fragility cohort (age ≥ 60, ISS < 16) and polytrauma cohort (age < 60, ISS ≥16), with both cohorts analyzed separately. Within each cohort, patients were split into three fixation timing groups: within 24 h, between 24 and 48 h, and greater than 48 h from presentation to the hospital. Fixation-timing groups were compared based on the primary outcome of in-hospital mortality rate. Secondary outcomes included hospital length of stay (LOS), ICU length of stay (ICU LOS), days on a ventilator, and complications.

RESULTS: The fragility and polytrauma cohorts included 22,045 and 5,905 patients, respectively. The in-hospital mortality rate was 1.23 % in …

Concurrent Optogenetic Motor Mapping Of Multiple Limbs In Awake Mice Reveals Cortical Organization Of Coordinated Movements, Nischal Khanal, Jonah A Padawer-Curry, Trevor Voss, Kevin A Schulte, Annie R Bice, Adam Q Bauer

2020-Current year OA Pubs

BACKGROUND: Motor mapping allows for determining the macroscopic organization of motor circuits and corresponding motor movement representations on the cortex. Techniques such as intracortical microstimulation (ICMS) are robust, but can be time consuming and invasive, making them non-ideal for cortex-wide mapping or longitudinal studies. In contrast, optogenetic motor mapping offers a rapid and minimally invasive technique, enabling mapping with high spatiotemporal resolution. However, motor mapping has seen limited use in tracking 3-dimensonal, multi-limb movements in awake animals. This gap has left open questions regarding the underlying organizational principles of motor control of coordinated, ethologically-relevant movements involving multiple limbs.

OBJECTIVE: Our …

Mean Arterial Pressure (Map) Augmentation In Traumatic Spinal Cord Injuries: Early Hyperperfusion Treatment Influences Neurologic Outcomes., Aimee K Lariccia, Kimberly Sperwer, Michael L Lieber, M Chance Spalding

Trauma and Acute Care Articles

Context: Hyperperfusion therapy, mean arterial blood pressure (MAP) > 85 mmHg, is a recommended treatment of blunt traumatic spinal cord injury (SCI). We hypothesized the first 24 h of MAP augmentation would be most influential on neurological outcomes.Design: This retrospective study from a level 1 urban trauma center dating 1/2017 to 12/2019 included all blunt traumatic spinal cord injured patients receiving hyperperfusion therapy. Patients were grouped as "No improvement" vs "Improvement" measured by change in American Spinal Injury Association (ASIA) score during their hospitalization. MAP values for the first 12, first 24 and last 72 h were compared between the …

Systemic Effects Of Anti-Vegf Intravitreal Injection In Patients With Age-Related Macular Degeneration: A Multi-Institutional Real-World Study, Tzu-Yi Lin, Yi-Ting Hsieh, Sunir J. Garg, Lee-Jen Chen, Kuan-Jen Chen, Wei-Chi Wu, Chi-Chun Lai, Yih-Shiou Hwang, Eugene Yu-Chuan Kang

Wills Eye Hospital Papers

PURPOSE: In individuals aged >50 years, age-related macular degeneration (AMD) is the leading cause of irreversible blindness. Intravitreal injections of antivascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab, and aflibercept) show good efficacy and similar incidences of systemic adverse events (SAEs). However, comparative studies between agents are limited. Our study aimed to compare the real-world SAE risks of bevacizumab, ranibizumab, and aflibercept users.

METHODS: This retrospective cohort study identified new bevacizumab, ranibizumab, and aflibercept users in a multi-institutional database in Taiwan between 2014 and 2019. Inverse probability of treatment weights (IPTW) with propensity scores was conducted to achieve homogeneity among …