Digital Commons Network^™

Vagus Nerve Stimulation In Treatment-Resistant Depression: A One-Year, Randomized, Sham-Controlled Trial, Charles R Conway, Christopher L Kriedt, Et Al.

2020-Current year OA Pubs

BACKGROUND: Few treatments are available for individuals with marked treatment-resistant depression (TRD).

OBJECTIVE: Evaluate the safety and effectiveness of FDA-approved adjunctive vagus nerve stimulation (VNS) in patients with marked TRD.

METHODS: This 12-month, multicenter, double-blind, sham-controlled trial included 493 adults with marked treatment-resistant major depression who were randomized to active or no-stimulation sham VNS for 12 months. The primary outcome was percent time in response across months 3-12, with response defined as a ≥50 % change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS). Several secondary endpoints were evaluated.

RESULTS: Overall, 88.4 % of participants completed the trial. Percent …

Effects Of Vagus Nerve Stimulation On Daily Function And Quality Of Life In Markedly Treatment-Resistant Major Depression: Findings From A One-Year, Randomized, Sham-Controlled Trial, A John Rush, Charles R Conway, Et Al.

2020-Current year OA Pubs

BACKGROUND: Depression treatments aim to minimize symptom burden and optimize quality of life (QoL) and psychosocial function.

OBJECTIVE: Compare the effects of adjunctive versus sham vagus nerve stimulation (VNS) on QoL and function in markedly treatment-resistant depression (TRD).

METHODS: In this multicenter, double-blind, sham-controlled trial, 493 adults with TRD and ≥4 adequate but unsuccessful antidepressant treatment trials (current episode) were randomized to active (n = 249) or sham (n = 244) VNS (plus treatment as usual) over a 12-month observation period. Quarterly outcomes included QoL with the Q-LES-Q, Mini-Q-LES-Q, and EQ-5D-5L, and function with the WHODAS 2.0 and Work Productivity …

Barriers And Facilitators To Implementing A Single-Visit, Screen-And-Treat Approach With Thermal Ablation For Cervical Cancer Prevention In Kenya, Harriet Fridah Adhiambo, Thomas Odeny, Et Al.

2020-Current year OA Pubs

Cervical cancer continues to be a major global threat to women's health, with approximately 660,000 women diagnosed annually, 94% of whom are in low- and middle-income countries (LMICs). The high disease burden in LMICs is partly due to suboptimal adoption and widespread implementation of effective preventive interventions. This study explored drivers of implementation success and failure for a future single-visit, screen, and treat approach with thermal ablation (SV-SAT + TA), referred to as TIBA in Kenya. Guided by the Consolidated Framework for Implementation Research (CFIR framework), we conducted in-depth interviews with 34 participants (frontline health workers, health facility managers, and …

Carpal Tunnel Syndrome And Occupational Co-Exposure To Biomechanical Factors And Neurotoxic Chemicals Using Job-Exposure Matrices And Self-Reported Exposure: Findings From The Constances Cohort, Julie Bodin, Clémence Rapicault, Alexis Descatha, Marc Fadel, Fabien Gilbert, Bradley Evanoff, Nathalie Bonvallot, Marcel Goldberg, Marie Zins, Yves Roquelaure

2020-Current year OA Pubs

OBJECTIVE: To study the association between occupational co-exposure to biomechanical risk factors, potentially neurotoxic chemicals and carpal tunnel syndrome (CTS) in a large cohort of French workers, using two methods to estimate chemical exposure: job-exposure matrices (JEM) and self-reported exposure.

METHODS: A randomly selected sample of adults were included between 2012 and 2018 in the French cohort CONSTANCES. Self-reported CTS was assessed using the first self-administered follow-up questionnaire, sent out approximately one year after baseline. Occupational exposure to biomechanical risk factors was assessed using self-administered questionnaire completed at inclusion. Lifetime occupational exposure to chemicals was assessed using two different methods: …

Colorectal Cancer Incidence Trends In Younger Versus Older Adults: An Analysis Of Population-Based Cancer Registry Data, Hyuna Sung, Rebecca L Siegel, Mathieu Laversanne, Chenxi Jiang, Eileen Morgan, Mariam Zahwe, Yin Cao, Freddie Bray, Ahmedin Jemal

2020-Current year OA Pubs

BACKGROUND: Previous studies have shown that colorectal cancer incidence is increasing among younger adults (aged < 50 years) in multiple high-income western countries in contrast with stabilising or decreasing trends in incidence in older adults (aged ≥50 years). This study aimed to investigate contemporary colorectal cancer incidence trends in younger adults versus older adults.

METHODS: Colorectal cancer incidence data, including year of diagnosis, sex, and 5-year age group for 50 countries and territories, were extracted from the WHO-International Agency for Research on Cancer Cancer Incidence in Five Continents Plus database. The Human Development Index 2022 was retrieved from the United Nations Development Programme and grouped into very high (>0·80), high (0·70-0·79), medium (0·55-0·69), and low (< 0·55) categories. Age-standardised incidence rates (ASR) per 100 000 person-years of early-onset (diagnosed between ages 25 to 49 years) and late-onset (diagnosed between ages 50 to 74 years) colorectal cancer (ICD 10th revision, C18-20), diagnosed between 1943-2003 and 2015-17, were calculated using the direct method and Segi-Doll world standard population). The primary study objective was to examine contemporary colorectal cancer incidence trends in younger adults versus older adults using data until 2017 from 50 countries and territories. Temporal trends were visualised and quantified with joinpoint regression, stratified by age at diagnosis (25-49 years or 50-74 years). Average annual percentage changes (AAPC) were estimated.

FINDINGS: In the most recent 5 years (2013-17 for all countries analysed, except for Japan [2011-15], Spain [2012-16], and Costa Rica [2012-16]), …

Recombinant Human Alpha-N-Acetylglucosamine-6-Sulfatase Delivered To Sanfilippo D Mice With Repeated Intracerebroventricular Injections Corrects Cns Pathology, Grant L. Austin, Feng Wang, Steven Q. Le, Alexander Sorensen, Shan Li, Lai C. Foong, Srikanth Singamsetty, Jill Wood, Tsui-Fen Chou, Patricia I. Dickson

2020-Current year OA Pubs

Mucopolysaccharidosis type IIID (MPS IIID; Sanfilippo D) is caused by biallelic pathogenic variants in N-acetylglucosamine-6-sulfatase (GNS), which participates in catabolism of heparan sulfate (HS) glycosaminoglycans. Characterization of MPS IIID disease at a cellular level has not been robustly achieved. We used unbiased quantitative proteomics to establish a cellular phenotype for MPS IIID mice. Recombinant human GNS (rhGNS), a variant of which previously demonstrated single dose efficacy in MPS IIID human fibroblasts and in MPS IIID neonatal mice, was used to establish a repeat dosing schedule to treat MPS IIID mice. Adult Gns KO mice or heterozygous carriers were treated via …

Development Of A High-Throughput Platform For Quantitation Of Histone Modifications On A New Qtof Instrument, Emily Zahn, Yixuan Xie, Xingyu Liu, Rashmi Karki, Richard M Searfoss, Francisca N De Luna Vitorino, Joanna K Lempiäinen, Joanna Gongora, Zongtao Lin, Chenfeng Zhao, Zuo-Fei Yuan, Benjamin A Garcia

2020-Current year OA Pubs

Histone post-translational modifications (PTMs) regulate gene expression patterns through epigenetic mechanisms. The five histone proteins (H1, H2A, H2B, H3, and H4) are extensively modified, with over 75 distinct modification types spanning more than 200 sites. Despite strong advances in mass spectrometry (MS)-based approaches, identification and quantification of modified histone peptides remains challenging because of factors, such as isobaric peptides, pseudo-isobaric PTMs, and low stoichiometry of certain marks. Here, we describe the development of a new high-throughput method to identify and quantify over 150 modified histone peptides by LC-MS. Fast gradient microflow liquid chromatography and variable window sequential windows acquisition of …

A Clinical Practice Review Of Optimizing The Approach For Correction Of Thoracolumbar Deformity— When And How To Perform Anterior Releases And Fusion, Brian M. Phelps, Munish C. Gupta

2020-Current year OA Pubs

No abstract provided.

Disclosing Disabilities: Barriers For Medical School Applicants, Sarah Leah Solomon, Aitan E. Magence, Harry Haran, Fern R. Juster, Kristina H. Petersen

2020-Current year OA Pubs

This study investigated the availability of accommodation request procedures for medical school admissions interviews and the accessibility of Technical Standards (TS) for candidates with disabilities (CWD) across Liaison Committee on Medical Education (LCME)-accredited institutions in the United States and Canada. Utilizing a cross-sectional study methodology, surveys were distributed to Deans of Admissions and Disabilities Resource Professionals (DRP) at all LCME-accredited US and Canadian MD programs. Surveys gathered data about interview formats, interview accommodation procedures, and TS accessibility during the 2018-2019 academic year. We received responses from 71 institutions (41.3%), with 56.3% survey completion rate (n = 40). Among respondents, interview …

Tourette Syndrome Research Highlights From 2024 [Version 3; Peer Review: 2 Approved, 1 Approved With Reservations], Andreas Hartmann, Per Andrén, Cyril Atkinson-Clement, Virginie Czernecki, Cécile Delorme, Simon Morand-Beaulieu, Nanette Mol Debes, Kirsten Müller-Vahl, Peristera Paschou, Natalia Szejko, Apostolia Topaloudi, Kevin J Black

2020-Current year OA Pubs

We summarize research reports from 2024 relevant to Tourette syndrome, which the authors consider the most important or interesting. This working draft aims to submit this content for publication around the beginning of 2025 in the yearly Tourette Syndrome Research Highlights series on F1000Research. The authors welcome article suggestions and thoughtful feedback from readers, who can add a comment by clicking on the rectangular comment box icon to the left of the LOG IN link at the top of this page. For private comments, you can reach us by email ( [email protected] or [email protected]).

Comparison And Clinical Applicability Analysis Of All-Posterior, Combined Anterior-Posterior, And Combined Lateral-Posterior Approaches In Adult Spinal Deformities: A Narrative Review, Garrison P. Bentz, Christopher Diaz, Nicholas A. Pollatta, Mark J. Lambrechts

2020-Current year OA Pubs

No abstract provided.

Treatment Of Hereditary Hemorrhagic Telangiectasias With Sclerotherapy: A Case Series, Jenny Ji, Andrew M Peterson, Jay F Piccirillo

2020-Current year OA Pubs

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is characterized by abnormal blood vessel formation. One treatment for HHT-related arteriovenous malformations (AVMs) is sclerotherapy, which collapses the blood vessels by irritating the endothelial lining.

METHODS: This case series describes two HHT patients undergoing in-office sodium tetradecyl sulfate sclerotherapy for non-nasal telangiectasias and AVMs. The first patient had AVMs on the red lip while the second patient had an AVM and several telangiectasias on the tongue.

RESULTS: Both patients' AVMs required only one treatment visit and were no longer noticeable within a week. Neither of the patients had any side effects from treatment.

CONCLUSION: …

Expert Consensus On The Diagnosis And Management Of Digoxin Toxicity, Jason B Hack, Sue Wingate, Ron Zolty, Michael W Rich, Paul J Hauptman

2020-Current year OA Pubs

While there has been a decline in the use of digoxin in patients with heart failure and atrial fibrillation, acute and chronic digoxin toxicity remains a significant clinical problem. Digoxin's narrow therapeutic window and nonspecific signs and symptoms of toxicity create clinical challenges and uncertainty around the diagnostic criteria of toxicity and responsive treatment choices for the bedside clinician. A systematic review of published literature on digoxin toxicity (34,587 publications over 6 decades, with 114 meeting inclusion criteria) was performed to develop 33 consensus statements on diagnostic and therapeutic approaches which were then evaluated through a modified Delphi process involving …

Validating A Novel Measure For Assessing Patient Openness And Concerns About Using Artificial Intelligence In Healthcare, Bryan A Sisk, Alison L Antes, Sunny C Lin, Paige Nong, James M Dubois

2020-Current year OA Pubs

OBJECTIVES: Patient engagement is critical for the effective development and use of artificial intelligence (AI)-enabled tools in learning health systems (LHSs). We adapted a previously validated measure from pediatrics to assess adults' openness and concerns about the use of AI in their healthcare.

STUDY DESIGN: Cross-sectional survey.

METHODS: We adapted the 33-item "Attitudes toward Artificial Intelligence in Healthcare for Parents" measure for administration to adults in the general US population (AAIH-A), recruiting participants through Amazon's Mechanical Turk (MTurk) crowdsourcing platform. AAIH-A assesses openness to AI-driven technologies and includes 7 subscales assessing participants' openness and concerns about these technologies. The openness …

Persistent Advanced Hiv Disease In Rural Kwazulu-Natal, South Africa: Trends, Characteristics, And The Urgent Need For Targeted Interventions, Marcel K. Kitenge, Geoffrey Fatti, Ingrid Eshun-Wilson, Peter S. Nyasulu

2020-Current year OA Pubs

BACKGROUND: Advanced HIV disease (AHD) remains a persistent public health challenge. Data regarding the burden, characteristics and predictors of AHD is scarce specifically for rural settings of sub-Saharan Africa. This study aimed to describe trends in annual CD4 count distribution and to characterise adult persons living with HIV (PLWH) on ART who have AHD in rural KwaZulu-Natal, South Africa.

METHODS: A retrospective cohort design of annual CD4 count distribution was conducted among antiretroviral therapy (ART) patients aged 18 years and older. We used routinely collected data from adults receiving ART in Eshowe and Mbongolwane areas in KwaZulu-Natal, South Africa, between …

Revisiting Abdominal Wall "Morbidity" Of The Extensile Anterolateral Approach To The Thoracolumbar Spine, Alekos A Theologis, Andrew P Collins, Kanwar Parhar, Munish C Gupta

2020-Current year OA Pubs

PURPOSE: To assess patients' perceptions of their abdominal wall following extensile anterolateral approaches to the thoracolumbar spine for adult spinal deformity (ASD) using validated questionnaires.

METHODS: Adults who underwent anterior-posterior thoracolumbar spinal operations to the pelvis for ASD in which the anterior fusion was performed through an extensile anterolateral approach were reviewed. Three questionnaires were administered at least 1 year following surgery and included The Abdominal Core Health Quality Collaborative Survey (AHS-QC), The Patient Scar Assessment Scale (PSAS), and The Anterior Abdominal Incision Questionnaire (AAIQ).

RESULTS: Fifty-one patients (80.4% female, median age 65 years) were included. Average follow-up was 2.8 …

Novel Loci For Triglyceride/Hdl-C Ratio Longitudinal Change Among Subjects Without T2d, Lihua Wang, Siyu Wang, Jason A Anema, Vaha A Moghaddam, Yanli Lu, Shiow Lin, E Warwick Daw, Allison L Kuipers, Iva Miljkovic, Michael Brent, Gary J Patti, Bharat Thygarajan, Joseph M Zmuda, Michael A Province, Ping An

2020-Current year OA Pubs

Triglyceride (TG)/HDL-C ratio (THR) is a surrogate predictor of hyperinsulinemia. To identify novel genetic loci for THR change over time (ΔTHR), we conducted genome-wide association study (GWAS) and genome-wide linkage scan (GWLS) among nondiabetic Europeans from the Long Life Family Study (n = 1,384). Subjects with diabetes or on dyslipidemia medications were excluded. ΔTHR was derived using growth curve modeling and adjusted for age, sex, field centers, and principal components. GWAS used a linear mixed model accounting for familial relatedness. GWLS employed haplotype-based identity-by-descent estimation with 0.5 cM average spacing. Heritability of ΔTHR was moderate (46%). Our GWAS identified a …

Measuring Stigma In Pediatric Oncology: A Cross-Sectional Analysis Of Three Global Sites, Lara E Counts, Sara M Malone, Et Al.

2020-Current year OA Pubs

PURPOSE: Stigma contributes to fear and shame, resulting in delays in care-seeking behavior among individuals with cancer. As a social construct, stigma is affected by language, religion, culture, and local norms. This study explored pediatric cancer stigma at the time of diagnosis across diverse settings through the adaptation of two stigma measures.

METHODS: This study was conducted with adolescents and caregivers of children with osteosarcoma and retinoblastoma at three centers in Jordan, Guatemala, and Zimbabwe. The Stigma-related Social Problems (SSP) and the eight-item Stigma Scale for Chronic Illness (SSCI-8) measures were translated into Arabic, Spanish, and Shona and contextually adapted …

Alternative Approaches For Monitoring And Evaluation Of Lymphatic Filariasis Following Mass Drug Treatment With Ivermectin, Diethylcarbamazine And Albendazole In East New Britain Province, Papua New Guinea, Krufinta Bun, Benedict Mode, Melinda Susapu, Joyceline Salo, Catherine Bjerum, Michael Payne, Daniel Tisch, Makoto Sekihara, Emanuele Giorgi, Gary J. Weil, Peter U. Fischer, Leanne Robinson, Moses Laman, Christopher L. King

2020-Current year OA Pubs

BACKGROUND: WHO recommends two annual rounds of mass drug administration (MDA) with ivermectin, diethylcarbamazine, and albendazole (IDA) for lymphatic filariasis (LF) elimination in treatment naïve areas that are not co-endemic for onchocerciasis such as Papua New Guinea (PNG). Whether two rounds of MDA are necessary or sufficient and the optimal sampling strategies and endpoints for stopping MDA remain undefined.

METHODS AND FINDINGS: Two cross-sectional studies were conducted at baseline (N = 49 clusters or villages) and 12 months after mass drug administration (MDA) with IDA (N = 47 villages) to assess lymphatic filariasis (LF) by circulating filarial antigenemia (CFA) and …

Patient Stratification By Genetic Risk In Alzheimer's Disease Is Only Effective In The Presence Of Phenotypic Heterogeneity, Jack Euesden, Muhammad Ali, Chloe Robins, Praveen Surendran, Padhraig Gormley, Alzheimer’S Disease Neuroimaging Initiative, David Pulford, Carlos Cruchaga

2020-Current year OA Pubs

Case-only designs in longitudinal cohorts are a valuable resource for identifying disease-relevant genes, pathways, and novel targets influencing disease progression. This is particularly relevant in Alzheimer's disease (AD), where longitudinal cohorts measure disease "progression," defined by rate of cognitive decline. Few of the identified drug targets for AD have been clinically tractable, and phenotypic heterogeneity is an obstacle to both clinical research and basic science. In four cohorts (n = 7241), we performed genome-wide association studies (GWAS) and Mendelian randomization (MR) to discover novel targets associated with progression and assess causal relationships. We tested opportunities for patient stratification by deriving …

Prevention And Management Of Posterior Wound Complications Following Oncologic Spine Surgery: Narrative Review Of Available Evidence And Proposed Clinical Decision-Making Algorithm, Owen P Leary, Matthew L Goodwin, Et Al.

2020-Current year OA Pubs

STUDY DESIGN: Narrative Review.

OBJECTIVE: Contextualized by a narrative review of recent literature, we propose a wound complication prevention and management algorithm for spinal oncology patients. We highlight available strategies and motivate future research to identify optimal and individualized wound management for this population.

METHODS: We conducted a search of recent studies (2010-2022) using relevant keywords to identify primary literature in support of current strategies for wound complication prevention and management following spine tumor surgery. When primary literature specific to spine tumor cases was not available, data were extrapolated from studies of other spine surgery populations. Results were compiled into …

Overview Of Molecular Prognostication For Common Solid Tumor Histologies - What The Surgeon Should Know, C Rory Goodwin, Matthew L Goodwin, Et Al.

2020-Current year OA Pubs

STUDY DESIGN: Narrative Literature review.

OBJECTIVE: To provide a general overview of important molecular markers and targeted therapies for the most common neoplasms (lung, breast, prostate and melanoma) that metastasize to the spine and offer guidance on how to best incorporate them in the clinical setting.

METHODS: A narrative review of the literature was performed using PubMed, Google Scholar, Medline databases, as well as the histology-specific National Comprehensive Cancer Network guidelines to identify relevant articles limited to the English language. Relevant articles were reviewed for commonly described molecular mutations or targeted therapeutics, as well as associated clinical outcomes, and surgery-related …

Evolution And Recent Radiation Therapy Advancement In Uganda: A Precedent On How To Increase Access To Quality Radiotherapy Services In Low- And Middle-Income Countries, Awusi Kavuma, Solomon Kibudde, Daniel Kanyike, Joseph Kigula-Mugambe, Tianyu Zhao, Hiram Gay, Baozhou Sun, Jackson Orem

2020-Current year OA Pubs

The evolution of radiation therapy in Uganda has been a journey marked by significant milestones and persistent challenges. Since the inception of radiotherapy services in 1988-1989, there has been a concerted effort to enhance cancer treatment services. The early years were characterized by foundational developments, such as the installation of the first teletherapy units, low-dose-rate brachytherapy units, and conventional simulators, and the recognition of radiation oncologists and medical physicist professionals laid the groundwork for radiotherapy treatment modalities. With more support from the International Atomic Energy Agency, the acquisition of dosimetry equipment, treatment planning systems, and additional professional training signaled a …

Menin Inhibition With Revumenib For Kmt2a-Rearranged Relapsed Or Refractory Acute Leukemia (Augment-101), Ghayas C Issa, John Dipersio, Et Al.

2020-Current year OA Pubs

PURPOSE: Revumenib, an oral, small molecule inhibitor of the menin-lysine methyltransferase 2A (KMT2A) interaction, showed promising efficacy and safety in a phase I study of heavily pretreated patients with

METHODS: AUGMENT-101 is a phase I/II, open-label, dose-escalation and expansion study of revumenib conducted across 22 clinical sites in five countries (ClinicalTrials.gov identifier: NCT04065399). We report results from the phase II, registration-enabling portion. Individuals age ≥30 days with R/R

RESULTS: From October 1, 2021, to July 24, 2023, N = 94 patients (median [range] age, 37 [1.3-75] years) were treated. Grade ≥3 adverse events included febrile neutropenia (37.2%), differentiation syndrome (16.0%), …

Social Anxiety, Negative Affect, And Hearing Difficulties In Adults, Katrina Kate S. Mcclannahan, Sarah Mcconkey, Julia M Levitan, Thomas L Rodebaugh, Jonathan E Peelle

2020-Current year OA Pubs

Subjective ratings of communication function reflect both auditory sensitivity and the situational, social, and emotional consequences of communication difficulties. Listeners interact with people and their environment differently, have various ways of handling stressful situations, and have diverse communication needs. Therefore, understanding the relationship between auditory and mental health factors is crucial for the holistic diagnosis and treatment of communication difficulty, particularly as mental health and communication function may have bidirectional effects. The goal of this study was to evaluate the degree to which social anxiety and negative affect (encompassing generalized anxiety, depression, and anger) contributed to subjective communication function (hearing …

Depression And Weight Loss Trajectories During An Integrated Behavioral Intervention: Within-Treatment Analysis Of The Rainbow Trial, Bailey W. Osweiler, Daphne Lew, Nan Lv, Jun Ma, Thomas G. Kannampallil

2020-Current year OA Pubs

INTRODUCTION: Depression and obesity are two of the most common chronic conditions among US adults. The Research Aimed at Improving Both Mood and Weight (RAINBOW) study was the first randomized clinical trial to demonstrate the effectiveness of an integrated behavioral treatment for depression and obesity. We aimed to characterize the trajectories of both depression symptoms and weight loss during the RAINBOW intervention.

METHODS: Participants (N = 201) randomly assigned to the RAINBOW treatment arm who provided serial data on depression symptoms (via the 9-item Patient Health Questionnaire [PHQ9]) and self-measured weight were included. Group-Based Multi-Trajectory Modeling is a statistical technique …

Mechanisms And Environmental Factors Shaping The Ecosystem Of Brain Macrophages, Silvia Penati, Simone Brioschi, Zhangying Cai, Claudia Z Han, Marco Colonna

2020-Current year OA Pubs

Brain macrophages encompass two major populations: microglia in the parenchyma and border-associated macrophages (BAMs) in the extra-parenchymal compartments. These cells play crucial roles in maintaining brain homeostasis and immune surveillance. Microglia and BAMs are phenotypically and epigenetically distinct and exhibit highly specialized functions tailored to their environmental niches. Intriguingly, recent studies have shown that both microglia and BAMs originate from the same myeloid progenitor during yolk sac hematopoiesis, but their developmental fates diverge within the brain. Several works have partially unveiled the mechanisms orchestrating the development of microglia and BAMs in both mice and humans; however, many questions remain unanswered. …

Case Report: Molecular Characterization Of Adult Atypical Teratoid Rhabdoid Tumor And Review Of The Literature, Miguel A Hernandez-Rovira, Michelle Connor, Robert C Osorio, Emilie Russler-Germain, Robert Schmidt, Gabrielle W Johnson, Julie Silverstein, Sonika Dahiya, Nyssa Fox Farrell, Mia C Weiss, Gregory J Zipfel, Jiayi Huang, Dimitrios Mathios

2020-Current year OA Pubs

BACKGROUND AND IMPORTANCE: Atypical teratoid rhabdoid tumors (ATRTs) are typically aggressive pediatric tumors with a median survival of 11 months. Due to the paucity of cases in adults, the clinical behavior of these pathologies is not well understood. Here we present the case of a 41-year-old female patient with postoperative hyperprogression of a sellar ATRT and provide a detailed description of the molecular composition of this tumor, the protocol used to treat this patient, and the ultimate outcome of this patient.

CLINICAL PRESENTATION: The patient is a 41-year-old woman who presented with headaches and double vision. MRI revealed a sellar/suprasellar …

Integrating Mapk Pathway Inhibition Into Standard-Of-Care Therapy For Pediatric Low-Grade Glioma, Erin E Crotty, Aimee A Sato, Mohamed S Abdelbaki

2020-Current year OA Pubs

Pediatric low-grade gliomas (pLGG) are a group of tumors largely driven by alterations in a single genetic pathway, known as the RAS-RAF-mitogen-activated protein kinase (MAPK) pathway. Recent biologic insights and therapeutic targeting of MAPK-alterations have dramatically shifted the treatment approach in pLGG. While chemotherapy remains front-line therapy for unresectable pLGG in most scenarios (with the notable exception of

Case Report: Rosah Syndrome Presents Diagnostic And Therapeutic Challenges, Jenny Shunyakova, Margaret Reynolds, Amal Taylor, Erin G Sieck, James T Walsh, Lynn M Hassman

2020-Current year OA Pubs

BACKGROUND: Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache (ROSAH) syndrome is an autosomal dominant disorder caused by a heterozygous missense mutation in alpha kinase 1 (ALPK1). This series reports the presentation and treatment outcomes of three first-degree relatives with ROSAH syndrome.

METHODS: Retrospective chart review, whole exome sequencing.

RESULTS: A 16-year-old male presented with bilateral optic disc edema, macular edema, retinal degeneration, and vitreous inflammation. His mother and brother had similar clinical features. Whole exome gene sequencing identified a shared heterozygous mutation in the ALPK1 gene c.710C>T, consistent with ROSAH syndrome. Ophthalmic manifestations in this family included …