Digital Commons Network^™

Better Operating Room Ventilation As Determined By A Novel Ventilation Index Is Associated With Lower Rates Of Surgical Site Infections, Bernard Surial, Andrew Atkinson, Rüdiger Külpmann, Arnold Brunner, Kurt Hildebrand, Benoît Sicre, Nicolas Troillet, Andreas Widmer, Eveline Rolli, Judith Maag, Jonas Marschall

2020-Current year OA Pubs

OBJECTIVE: The aim was to assess the impact of operating room (OR) ventilation quality on surgical site infections (SSIs) using a novel ventilation index.

BACKGROUND: Previous studies compared laminar air flow with conventional ventilation, thereby ignoring many parameters that influence air flow properties.

METHODS: In this cohort study, we surveyed hospitals participating in the Swiss SSI surveillance and calculated a ventilation index for their ORs, with higher values reflecting less turbulent air displacement. For procedures captured between January 2017 and December 2019, we studied the association between ventilation index and SSI rates using linear regression (hospital-level analysis) and with the …

Assessment Of Infectious Diseases Risks From Dental Aerosols In Real-World Settings, Shruti Choudhary, Tracey Bach, Meghan A Wallace, Daniel C Stoeckel, Martin H Thornhill, Peter B Lockhart, Jennie H Kwon, Stephen Y Liang, Carey-Ann D Burnham, Pratim Biswas, Heidi M Steinkamp, Michael J Durkin

2020-Current year OA Pubs

BACKGROUND: Infectious diseases physicians are leaders in assessing the health risks in a variety of community settings. An understudied area with substantial controversy is the safety of dental aerosols. Previous studies have used in vitro experimental designs and/or indirect measures to evaluate bacteria and viruses from dental surfaces. However, these findings may overestimate the occupational risks of dental aerosols. The purpose of this study was to directly measure dental aerosol composition to assess the health risks for dental healthcare personnel and patients.

METHODS: We used a variety of aerosol instruments to capture and measure the bacterial, viral, and inorganic composition …

Human Immunodeficiency Virus Pre-Exposure Prophylaxis Knowledge, Attitudes, And Self-Efficacy Among Family Planning Providers In The Southern United States: Bridging The Gap In Provider Training, Aditi Ramakrishnan, Jessica M Sales, Micah Mccumber, Leah Powell, Anandi N Sheth

2020-Current year OA Pubs

BACKGROUND: Pre-exposure prophylaxis (PrEP) is an effective human immunodeficiency virus (HIV) prevention intervention, but its access and use are suboptimal, especially for women. Healthcare providers provision of PrEP is a key component of the

METHODS: We used data from providers in clinics that did not currently provide PrEP from a web-based survey administered to Title X clinic staff in 18 Southern states from February to June 2018. We developed generalized linear mixed models to evaluate associations between provider-, clinic-, and county-level variables with provider knowledge, attitudes, and self-efficacy in PrEP care, guided by the Consolidated Framework for Implementation Research.

RESULTS: …

Association Of Noncontrast Computed Tomography And Perfusion Modalities With Outcomes In Patients Undergoing Late-Window Stroke Thrombectomy, Guilherme B F Porto, Joshua Osbun, Et Al.

2020-Current year OA Pubs

IMPORTANCE: There is substantial controversy with regards to the adequacy and use of noncontrast head computed tomography (NCCT) for late-window acute ischemic stroke in selecting candidates for mechanical thrombectomy.

OBJECTIVE: To assess clinical outcomes of patients with acute ischemic stroke presenting in the late window who underwent mechanical thrombectomy stratified by NCCT admission in comparison with selection by CT perfusion (CTP) and diffusion-weighted imaging (DWI).

DESIGN, SETTING, AND PARTICIPANTS: In this multicenter retrospective cohort study, prospectively maintained Stroke Thrombectomy and Aneurysm (STAR) database was used by selecting patients within the late window of acute ischemic stroke and emergent large vessel …

Upper Limb Nerve Transfer Surgery In Patients With Tetraplegia, Saad Javeed, Christopher F Dibble, Jacob K Greenberg, Justin K Zhang, Jawad M Khalifeh, Yikyung Park, Thomas J Wilson, Eric L Zager, Amir H Faraji, Mark A Mahan, Lynda J Yang, Rajiv Midha, Neringa Juknis, Wilson Z Ray

2020-Current year OA Pubs

IMPORTANCE: Cervical spinal cord injury (SCI) causes devastating loss of upper extremity function and independence. Nerve transfers are a promising approach to reanimate upper limbs; however, there remains a paucity of high-quality evidence supporting a clinical benefit for patients with tetraplegia.

OBJECTIVE: To evaluate the clinical utility of nerve transfers for reanimation of upper limb function in tetraplegia.

DESIGN, SETTING, AND PARTICIPANTS: In this prospective case series, adults with cervical SCI and upper extremity paralysis whose recovery plateaued were enrolled between September 1, 2015, and January 31, 2019. Data analysis was performed from August 2021 to February 2022.

INTERVENTIONS: Nerve …

Engineering Diverse Fatty Acid Compositions Of Phospholipids In Escherichia Coli, Wenqin Bai, Winston E Anthony, Christopher J Hartline, Shaojie Wang, Bin Wang, Jie Ning, Fong-Fu Hsu, Gautam Dantas, Fuzhong Zhang

2020-Current year OA Pubs

Bacterial fatty acids (FAs) are an essential component of the cellular membrane and are an important source of renewable chemicals as they can be converted to fatty alcohols, esters, ketones, and alkanes, and used as biofuels, detergents, lubricants, and commodity chemicals. Most prior FA bioconversions have been performed on the carboxylic acid group. Modification of the FA hydrocarbon chain could substantially expand the structural and functional diversity of FA-derived products. Additionally, the effects of such modified FAs on the growth and metabolic state of their producing cells are not well understood. Here we engineer novel Escherichia coli phospholipid biosynthetic pathways, …

Clinical Characteristics Of Children With Cerebral Injury Preceding Treatment Of Diabetic Ketoacidosis, Nicole S Glaser, Kimberly S Quayle, Et Al.

2020-Current year OA Pubs

Previous studies have identified more severe acidosis and higher blood urea nitrogen (BUN) as risk factors for cerebral injury during treatment of diabetic ketoacidosis (DKA) in children; however, cerebral injury also can occur before DKA treatment. We found that lower pH and higher BUN levels also were associated with cerebral injury at presentation.

A Randomized Phase Ii Study Of Sm-88 Plus Methoxsalen, Phenytoin, And Sirolimus In Patients With Metastatic Pancreatic Cancer Treated In The Second Line And Beyond, Marcus S Noel, Semmie Kim, Marion L Hartley, Steve Wong, Vincent J Picozzi, Harry Staszewski, Dae Won Kim, Jan M Van Tornout, Philip Agop Philip, Vincent Chung, Allyson J Ocean, Andrea Wang-Gillam

2020-Current year OA Pubs

BACKGROUND: This trial explores SM-88 used with methoxsalen, phenytoin, and sirolimus (MPS) in pretreated metastatic pancreatic ductal adenocarcinoma (mPDAC) METHODS: Forty-nine patients were randomized to daily 460 or 920 mg oral SM-88 with MPS (SM-88 Regimen). The primary endpoint was objective response rate (RECIST 1.1).

RESULTS: Thirty-seven patients completed ≥ one cycle of SM-88 Regimen (response evaluable population). Disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) did not differ significantly between dose levels. Stable disease was achieved in 9/37 patients (DCR, 24.3%); there were no complete or partial responses. Quality-of-life (QOL) was maintained and trended in favor …

Importance Of First Pass Reperfusion In Endovascular Stroke Care - Insights From Thrombectomy And Aneurysm Registry (Star), Ilko L Maier, Joshua Osbun, Et Al.

2020-Current year OA Pubs

BACKGROUND: Mechanical thrombectomy has become the first-line treatment strategy for patients with large-vessel occlusion strokes. Often >1 thrombectomy maneuver is necessary to achieve reperfusion. A first-pass (FP) effect with improved functional outcomes after mechanical thrombectomy has been described. Aim of the present study is to investigate the FP effect in a large, international, multicenter stroke database.

METHODS: Patients who underwent mechanical thrombectomy for large-vessel occlusion stroke in the anterior cerebral circulation between January 2014 and January 2021 and achieved complete reperfusion were identified from the STAR (Stroke Thrombectomy and Aneurysm Registry). We compared functional outcomes of patients with FP (defined …

Real-World Evidence Supporting Tandem Control-Iq Hybrid Closed-Loop Success In The Medicare And Medicaid Type 1 And Type 2 Diabetes Populations, Gregory P Forlenza, Anders L Carlson, Rodolfo J Galindo, Davida F Kruger, Carol J Levy, Janet B Mcgill, Guillermo Umpierrez, Grazia Aleppo

2020-Current year OA Pubs

No abstract provided.

Ventilation Strategies During Extracorporeal Membrane Oxygenation For Neonatal Respiratory Failure: Current Approaches Among Level Iv Neonatal Icus, John Ibrahim, Rakesh Rao, Et Al.

2020-Current year OA Pubs

UNLABELLED: To describe ventilation strategies used during extracorporeal membrane oxygenation (ECMO) for neonatal respiratory failure among level IV neonatal ICUs (NICUs).

DESIGN: Cross-sectional electronic survey.

SETTING: Email-based Research Electronic Data Capture survey.

PATIENTS: Neonates undergoing ECMO for respiratory failure at level IV NICUs.

INTERVENTIONS: A 40-question survey was sent to site sponsors of regional referral neonatal ECMO centers participating in the Children's Hospitals Neonatal Consortium. Reminder emails were sent at 2- and 4-week intervals.

MEASUREMENTS AND MAIN RESULTS: Twenty ECMO centers responded to the survey. Most primarily use venoarterial ECMO (65%); this percentage is higher (90%) for congenital diaphragmatic hernia. …

Amyloid-Β And Tau Deposition Influences Cognitive And Functional Decline In Down Syndrome, Monika Grigorova, Beau Ances, Et Al.

2020-Current year OA Pubs

This study investigates whether tau has (i) an independent effect from amyloid-β on changes in cognitive and functional performance and (ii) a synergistic relationship with amyloid-β in the exacerbation of decline in aging Down syndrome (DS). 105 participants with DS underwent baseline PET [

Covariance-Based Vs. Correlation-Based Functional Connectivity Dissociates Healthy Aging From Alzheimer Disease, Jeremy F. Strain, Matthew R. Brier, Aaron Tanenbaum, Brian A. Gordon, John E. Mccarthy, Aylin Dincer, Daniel S. Marcus, Richard J. Perrin, John C. Morris, Tammie L. S. Benzinger, Randall J. Bateman, Beau M. Ances, Abraham Z. Snyder, Et Al.

2020-Current year OA Pubs

Prior studies of aging and Alzheimer disease have evaluated resting state functional connectivity (FC) using either seed-based correlation (SBC) or independent component analysis (ICA), with a focus on particular functional systems. SBC and ICA both are insensitive to differences in signal amplitude. At the same time, accumulating evidence indicates that the amplitude of spontaneous BOLD signal fluctuations is physiologically meaningful. We systematically compared covariance-based FC, which is sensitive to amplitude, vs. correlation-based FC, which is not, in affected individuals and controls drawn from two cohorts of participants including autosomal dominant Alzheimer disease (ADAD), late onset Alzheimer disease (LOAD), and age-matched …

Transgenic Force Sensors And Software To Measure Force Transmission Across The Mammalian Nuclear Envelope In Vivo, Kelli D Fenelon, Evan Thomas, Mohammad Samani, Min Zhu, Hirotaka Tao, Yu Sun, Helen Mcneill, Sevan Hopyan

2020-Current year OA Pubs

Nuclear mechanotransduction is a growing field with exciting implications for the regulation of gene expression and cellular function. Mechanical signals may be transduced to the nuclear interior biochemically or physically through connections between the cell surface and chromatin. To define mechanical stresses upon the nucleus in physiological settings, we generated transgenic mouse strains that harbour FRET-based tension sensors or control constructs in the outer and inner aspects of the nuclear envelope. We knocked-in a published esprin-2G sensor to measure tensions across the LINC complex and generated a new sensor that links the inner nuclear membrane to chromatin. To mitigate challenges …

Associations Between Transcranial Doppler Vasospasm And Clinical Outcomes After Aneurysmal Subarachnoid Hemorrhage: A Retrospective Observational Study, Abhijit V. Lele, Rafael Wabl, Sarah Wahlster, Jade Keen, Andrew M. Walters, Christine T. Fong, Vasu B. Dhulipala, Umeshkumar Athiraman, Anne Moore, Monica S. Vavilala, Louis J. Kim, Michael R. Levitt

2020-Current year OA Pubs

OBJECTIVE: The objective is to examine the relationship between transcranial Doppler cerebral vasospasm (TCD-vasospasm), and clinical outcomes in aneurysmal subarachnoid hemorrhage (aSAH).

METHODS: In a retrospective cohort study, using univariate and multivariate analysis, we examined the association between TCD-vasospasm (defined as Lindegaard ratio >3) and patient's ability to ambulate without assistance, the need for tracheostomy and gastrostomy tube placement, and the likelihood of being discharged home from the hospital.

RESULTS: We studied 346 patients with aSAH; median age 55 years (Interquartile range IQR 46,64), median Hunt and Hess 3 [IQR 1-5]. Overall, 68.6% (n=238) had TCD-vasospasm, and 28% (n=97) had …

Quantitative Tumor Depth Determination Using Dual Wavelength Excitation Fluorescence, Christine M. O'Brien, Kevin W. Bishop, Haini Zhang, Xiao Xu, Leo Shmuylovich, Elizabeth Conley, Karen Nwosu, Kathleen Duncan, Suman B. Mondal, Gail Sudlow

2020-Current year OA Pubs

No abstract provided.

Self-Care Management Of Bothersome Symptoms As Recommended By Clinicians For Patients With A Chronic Condition: A Delphi Study, Heleen Westland, Shayleigh Dickson Page, Michelle Van Rijn, Subhash Aryal, Kenneth E Freedland, Christopher Lee, Anna Strömberg, Ercole Vellone, Douglas J Wiebe, Tiny Jaarsma, Barbara Riegel

2020-Current year OA Pubs

BACKGROUND: Chronically medically ill patients often need clinical assistance with symptom management, as well as self-care interventions that can help to reduce the impact of bothersome symptoms. Experienced clinicians can help to guide the development of more effective self-care interventions.

OBJECTIVE: To create a consensus-based list of common bothersome symptoms of chronic conditions and of self-care management behaviors recommended to patients by clinicians to reduce the impact of these symptoms.

METHODS: A two-round Delphi study was performed among an international panel of 47 clinicians using online surveys to identify common and bothersome symptoms and related self-care management behaviors recommended to …

Guidance For The Diagnosis And Treatment Of Hypolipidemia Disorders, Cindy Bredefeld, Nicholas O Davidson, Et Al.

2020-Current year OA Pubs

The Abetalipoproteinemia and Related Disorders Foundation was established in 2019 to provide guidance and support for the life-long management of inherited hypocholesterolemia disorders. Our mission is "to improve the lives of individuals and families affected by abetalipoproteinemia and related disorders". This review explains the molecular mechanisms behind the monogenic hypobetalipoproteinemia disorders and details their specific pathophysiology, clinical presentation and management throughout the lifespan. In this review, we focus on abetalipoproteinemia, homozygous hypobetalipoproteinemia and chylomicron retention disease; rare genetic conditions that manifest early in life and cause severe complications without appropriate treatment. Absent to low plasma lipid levels, in particular cholesterol …

To Calibrate Or Not To Calibrate? A Methodological Dilemma In Experimental Pain Research, Waclaw M Adamczyk, Tibor M Szikszay, Hadas Nahman-Averbuch, Jacek Skalski, Jakub Nastaj, Philip Gouverneur, Kerstin Luedtke

2020-Current year OA Pubs

To calibrate or not to calibrate? This question is raised by almost everyone designing an experimental pain study with supra-threshold stimulation. The dilemma is whether to individualize stimulus intensity to the pain threshold / supra-threshold pain level of each participant or whether to provide the noxious stimulus at a fixed intensity so that everyone receives the identical input. Each approach has unique pros and cons which need to be considered to i) accurately design an experiment, ii) enhance statistical inference in the given data and, iii) reduce bias and the influence of confounding factors in the individual study e.g., body …

Local Failure Events In Prostate Cancer Treated With Radiotherapy: A Pooled Analysis Of 18 Randomized Trials From The Meta-Analysis Of Randomized Trials In Cancer Of The Prostate Consortium (Leviathan), Ting Martin Ma, Jeff M Michalski, Et Al.

2020-Current year OA Pubs

CONTEXT: The prognostic importance of local failure after definitive radiotherapy (RT) in National Comprehensive Cancer Network intermediate- and high-risk prostate cancer (PCa) patients remains unclear.

OBJECTIVE: To evaluate the prognostic impact of local failure and the kinetics of distant metastasis following RT.

EVIDENCE ACQUISITION: A pooled analysis was performed on individual patient data of 12 533 PCa (6288 high-risk and 6245 intermediate-risk) patients enrolled in 18 randomized trials (conducted between 1985 and 2015) within the Meta-analysis of Randomized Trials in Cancer of the Prostate Consortium. Multivariable Cox proportional hazard (PH) models were developed to evaluate the relationship between overall survival …

Hospital Trajectories And Early Predictors Of Clinical Outcomes Differ Between Sars-Cov-2 And Influenza Pneumonia, Patrick G Lyons, Aaloke Mody, Alice Bewley, Katherine Dittman, Aisling Doyle, Samuel L Windham, Tej M Patel, Bharat Neelam Raju, Matthew Keller, Andrew P Michelson, Thomas Kannampallil, Elvin H Geng, Pratik Sinha, Et Al.

2020-Current year OA Pubs

BACKGROUND: A comparison of pneumonias due to SARS-CoV-2 and influenza, in terms of clinical course and predictors of outcomes, might inform prognosis and resource management. We aimed to compare clinical course and outcome predictors in SARS-CoV-2 and influenza pneumonia using multi-state modelling and supervised machine learning on clinical data among hospitalised patients.

METHODS: This multicenter retrospective cohort study of patients hospitalised with SARS-CoV-2 (March-December 2020) or influenza (Jan 2015-March 2020) pneumonia had the composite of hospital mortality and hospice discharge as the primary outcome. Multi-state models compared differences in oxygenation/ventilatory utilisation between pneumonias longitudinally throughout hospitalisation. Differences in predictors of …

Infectious Complications Of Abortion, L. Lewis Wall, Awol Yemane

2020-Current year OA Pubs

This article reviews the infectious complications of abortion (both spontaneous and induced) and the management of this condition. The key points are: (1) Making abortion illegal does not reduce its incidence or prevalence; rather, it only makes abortions unsafe, increasing the likelihood of infectious complications. (2) Timely recognition of developing sepsis in the pregnant patient is critical. This requires constant vigilance and a high index of suspicion. (3) Rapid intravenous administration of broad-spectrum antibiotics targeted to the likely intrauterine source of infection as soon as sepsis is diagnosed is critical to prevent severe sepsis, septic shock, and multisystem organ failure. …

Comparison Of Indirect Fungal Diagnostic Tests In Patients With Proven Histoplasmosis, Gayathri Krishnan, Margaret Power, J Ryan Bariola, Ryan Dare

2020-Current year OA Pubs

BACKGROUND: Histoplasmosis is a common cause of invasive fungal infection in endemic regions and accurate diagnosis is difficult without direct tissue culture or pathology. Indirect fungal antigen testing for various fungal pathogens are typically performed to assist with diagnostic workup, though cross-reaction can lead to difficulty in interpreting results. We aimed to compare indirect fungal diagnostic tests and evaluate prevalence of positive antigen testing for non-

METHODS: We performed a single-center retrospective review of adult patients with proven histoplasmosis diagnosed by fungal culture and/or cytology from January 2010 to March 2018. Patient demographics, clinical characteristics, and results of fungal antigen …

Profilin-1 Regulates Dna Replication Forks In A Context-Dependent Fashion By Interacting With Snf2h And Bod1l, Cuige Zhu, Mari Iwase, Ziqian Li, Faliang Wang, Annabel Quinet, Alessandro Vindigni, Jieya Shao

2020-Current year OA Pubs

DNA replication forks are tightly controlled by a large protein network consisting of well-known core regulators and many accessory factors which remain functionally undefined. In this study, we report previously unknown nuclear functions of the actin-binding factor profilin-1 (PFN1) in DNA replication, which occur in a context-dependent fashion and require its binding to poly-L-proline (PLP)-containing proteins instead of actin. In unperturbed cells, PFN1 increases DNA replication initiation and accelerates fork progression by binding and stimulating the PLP-containing nucleosome remodeler SNF2H. Under replication stress, PFN1/SNF2H increases fork stalling and functionally collaborates with fork reversal enzymes to enable the over-resection of unprotected …

An Assessment Of Pediatric Residency Applicant Perceptions Of "Fit" During The Virtual Interview Era, Jason D. Vadhan, Jorge G. Zarate Rodriguez, Michael Wallendorf, Michael M. Awad, Andrew J. White

2020-Current year OA Pubs

PURPOSE: Residency recruitment events and interviews are widely considered an integral component of the residency match experience. Due to the COVID-19 pandemic, residency recruitment and interviewing throughout the 2020-2021 academic year were performed virtually, which created challenges for applicants' ability to discern "fit" to a program. Given this change, it is reasonable to suspect that applicants would be less able to discern program fit. Therefore, this study evaluated how virtual interviews impacted pediatric residency applicants' ability to assess factors contributing to fit and subsequently how applicants assessed their self-perceived fit to their top-ranked programs.

METHODS: An online, anonymous survey was …

Inositol Phosphorylceramide Synthase Null Leishmania Are Viable And Virulent In Animal Infections Where Salvage Of Host Sphingomyelin Predominates, F Matthew Kuhlmann, Phillip N Key, Suzanne M Hickerson, John Turk, Fong-Fu Hsu, Stephen M Beverley

2020-Current year OA Pubs

Many pathogens synthesize inositol phosphorylceramide (IPC) as the major sphingolipid (SL), differing from the mammalian host where sphingomyelin (SM) or more complex SLs predominate. The divergence between IPC synthase and mammalian SL synthases has prompted interest as a potential drug target. However, in the trypanosomatid protozoan Leishmania, cultured insect stage promastigotes lack de novo SL synthesis (Δspt2

Brain Volume In Chronic Ketamine Users - Relationship To Sub-Threshold Psychotic Symptoms And Relevance To Schizophrenia, Robert A Chesters, Fiona Pepper, Celia Morgan, Jonathan D Cooper, Oliver D Howes, Anthony C Vernon, James M Stone

2020-Current year OA Pubs

RATIONALE: Ketamine may model aspects of schizophrenia arising through NMDA receptor activity deficits. Although acute ketamine can induce effects resembling both positive and negative psychotic symptoms, chronic use may be a closer model of idiopathic psychosis.

OBJECTIVES: We tested the hypotheses that ketamine users had lower brain volumes, as measured using MRI, and greater sub-threshold psychotic symptoms relative to a poly-drug user control group.

METHODS: Ketamine users (n = 17) and poly-drug using controls (n = 19) were included in the study. All underwent volumetric MRI imaging and measurement of sub-threshold psychotic symptoms using the Comprehensive Assessment of At-Risk Mental …

Age-Dependent Rebound In Asthma Exacerbations After Covid-19 Lockdown, Guy Hazan, Carolyn Fox, Huram Mok, Jeffrey Haspel

2020-Current year OA Pubs

BACKGROUND: Virus mitigation measures enacted early in the coronavirus infectious disease 2019 (COVID-19) pandemic suppressed common respiratory viruses and reduced the number of obstructive lung disease exacerbations. However, many localities began to ease these precautions in the year 2021, leading to a resurgence of non-COVID viruses. How asthma and chronic obstructive pulmonary disease (COPD) activity responded to this upswing in viral abundance is unclear.

OBJECTIVE: Our aim was to examine how viral resurgence during the relaxation of COVID-19 restrictions affected asthma and COPD exacerbations.

METHODS: We analyzed electronic medical records for emergency department (ED) respiratory virus positivity, asthma visits, and …

Pembrolizumab For Patients With Non-Hodgkin Lymphoma: Phase 1b Keynote-013 Study, John Kuruvilla, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

The multicohort phase 1b KEYNOTE-013 study (NCT01953692) evaluated the safety and efficacy of pembrolizumab in patients with relapsed or refractory NHL who were ineligible for or failed hematopoietic cell transplantation (HCT). Patients received pembrolizumab (cohort 4) or pembrolizumab plus lenalidomide (cohort 5). Primary end points were safety and objective response rate (ORR) per IWG 2007 criteria. Cohort 4 included 89 patients. ORR was 22% (19/86; 90% CI 15-31; 10 CR, nine PR); ORRs by disease type were 48% (10/21), 10% (2/20), 12% (5/41), and 50% (2/4), for PMBCL, FL, DLBCL, and 'other' NHL, respectively. Toxicity was as predicted. Cohort 5 …

Dose-Dependent Seizure Control With Mek Inhibitor Therapy For Progressive Glioma In A Child With Neurofibromatosis Type 1, Evan Cantor, Ashley Meyer, Stephanie M Morris, Judith L Z Weisenberg, Nicole M Brossier

2020-Current year OA Pubs

BACKGROUND: Low-grade gliomas (LGGs) occurring in children can result in many different neurologic complications, including seizures. MEK inhibitors are increasingly being used to treat LGG, but their effect on associated neurologic symptoms has not been established.

RESULTS: Here, we report a patient with neurofibromatosis type 1 (NF1), medically refractory epilepsy (MRE), and an extensive optic pathway glioma (OPG) who developed dose-dependent seizure control while being treated with selumetinib. Seizure frequency rebounded after dose reduction for cardiac toxicity, then improved, and finally ceased after restarting full dosing, allowing confidence in the cause of improvement.

CONCLUSION: Selumetinib may have promise in epilepsy …