Medicine and Health Sciences Commons^™

Modeling The Prognostic Impact Of Circulating Tumor Cells Enumeration In Metastatic Breast Cancer For Clinical Trial Design Simulation, Lorenzo Gerratana, Andrew A Davis, Et Al.

2020-Current year OA Pubs

Despite the strong prognostic stratification of circulating tumor cells (CTCs) enumeration in metastatic breast cancer (MBC), current clinical trials usually do not include a baseline CTCs in their design. This study aimed to generate a classifier for CTCs prognostic simulation in existing datasets for hypothesis generation in patients with MBC. A K-nearest neighbor machine learning algorithm was trained on a pooled dataset comprising 2436 individual MBC patients from the European Pooled Analysis Consortium and the MD Anderson Cancer Center to identify patients likely to have CTCs ≥ 5/7 mL blood (StageIVaggressive vs StageIVindolent). The model had a 65.1% accuracy and …

Prediction Of Patient Outcomes Through Social Determinants Of Health: The Pulmonary Hypertension Association Registry (Phar) Evaluation, Dan Grinnan, Murali Chakinala, Et Al.

2020-Current year OA Pubs

Outcomes of patients with pulmonary arterial hypertension (PAH) may be associated with social determinants of health (SDOH) and other baseline patient characteristics. At present, there is no prognostic model to predict important patient outcomes in PAH based on SDOH. Utilizing information from the Pulmonary Hypertension Association Registry (PHAR), we derive a model (PHAR Evaluation or PHARE) to predict an important composite patient outcomes based on SDOH and other patient characteristics. Baseline data regarding SDOH from adult patients with PAH enrolled in the PHAR between 2015 and March 23, 2020, were included for analysis. We performed repeated measures logistic regression modeling …

Impact Of The Covid-19 Pandemic On Daily Life, Mood, And Behavior Of Adults With Down Syndrome, Sigan L Hartley, Beau M Ances, Et Al.

2020-Current year OA Pubs

BACKGROUND: The Down syndrome population has been disproportionately affected by Coronavirus 2019 (COVID-19) in terms of experiencing severe illness and death. Societal efforts to curb the spread of COVID-19 may also have taken a heavy toll on the daily lives of individuals with Down syndrome.

OBJECTIVE/HYPOTHESIS: The goal of the study was to understand how the COVID-19 pandemic has altered daily life (including residence, employment, and participation in adult disability day programs) and influenced the mood and behavior of adults with Down syndrome.

METHODS: Between September 2020 and February 2021, caregivers of 171 adults with Down syndrome (aged 22-66 years) …

Changes In Adiposity Over The Life Course And Gene Expression In Postmenopausal Women, Yunan Han, Graham A Colditz, Adetunji T Toriola

2020-Current year OA Pubs

BACKGROUND: Early life adiposity and changes in adiposity over the life course are associated with mammographic breast density among postmenopausal women. However, the underlying mechanisms are unknown; therefore, we comprehensively examined the associations of early life body mass index (BMI) and changes in BMI from ages 10, 18 to age at mammogram with growth factor, RANK pathway, and sex hormone gene expression in 372 postmenopausal women.

METHODS: We estimated early life BMI at age 10 using the validated 9-level Stunkard pictogram. We calculated BMI at other ages (18, 30, and current age at mammogram) by dividing weight in kilograms at …

Environmental Conditions To Promote Healthy Childhood Brain/Behavioral Development: Informing Early Preventive Interventions For Delivery In Routine Care, Joan L Luby, Cynthia Rogers, Katie A Mclaughlin

2020-Current year OA Pubs

Environmental experiences early in life have strong and enduring consequences for cognitive, emotional, and neurobiological development and related physical and mental health trajectories. The powerful influence of early caregiver nurturance and stimulation on promoting positive neurodevelopmental outcomes has been demonstrated across species. These findings elucidate the environmental conditions known to facilitate healthy neurodevelopment and underscore the potential for modifiable psychosocial factors in the environment to be harnessed to inform early preventive interventions to promote health and adaptive development. A framework for early preventive interventions to enhance nurturing and responsive caregiving for implementation during early sensitive periods of brain development delivered …

Outcomes After Intracranial Rescue Stenting For Acute Ischemic Stroke, Christine Tschoe, Joshua Osbun, Et Al.

2020-Current year OA Pubs

BACKGROUND: In cases of failed recanalization despite modern mechanical thrombectomy (MT) techniques, intracranial rescue stenting (RS) may be beneficial. However, outcomes and complications of RS relative to the natural history of ongoing emergent large vessel occlusion are unknown. To evaluate whether RS for ongoing emergent large vessel occlusion after failed MT achieves superior outcomes to the natural history of persistent emergent large vessel occlusion.

METHODS: Patients from the Stroke Thrombectomy and Aneurysm Registry who underwent RS after failed MT from 2014 to 2019 were analyzed. For outcome comparisons, patients were screened for inclusion/exclusion criteria of 3 major randomized, controlled MT …

Accuracy And Reliability Of Diffusion Imaging Models, Nicole A. Seider, Babatunde Adeyemo, Ryland Miller, Dillan J. Newbold, Jacqueline M. Hampton, Kristen M. Scheidter, Jerrel Rutlin, Timothy O. Laumann, Jarod L. Roland, David F. Montez, Andrew N. Van, Annie Zheng, Scott Marek, Benjamin P. Kay, G. Larry Bretthorst, Yong Wang, Steven E. Petersen, Deanna M. Barch, Evan M. Gordon, Abraham Z. Snyder, Joshua S. Shimony, Nico U. F. Dosenbach

2020-Current year OA Pubs

Diffusion imaging aims to non-invasively characterize the anatomy and integrity of the brain's white matter fibers. We evaluated the accuracy and reliability of commonly used diffusion imaging methods as a function of data quantity and analysis method, using both simulations and highly sampled individual-specific data (927-1442 diffusion weighted images [DWIs] per individual). Diffusion imaging methods that allow for crossing fibers (FSL's BedpostX [BPX], DSI Studio's Constant Solid Angle Q-Ball Imaging [CSA-QBI], MRtrix3's Constrained Spherical Deconvolution [CSD]) estimated excess fibers when insufficient data were present and/or when the data did not match the model priors. To reduce such overfitting, we developed …

A Staged Reconstruction Technique Utilizing Bioprosthetic Mesh Reinforcement In The Repair Of Giant Omphalocele, Annahita R. Fotouhi, Justin M. Sacks, Martin S. Keller, Kamlesh B. Patel

2020-Current year OA Pubs

No abstract provided.

Retrospective Analysis Of Pacritinib In Patients With Myelofibrosis And Severe Thrombocytopenia, Srdan Verstovsek, Ruben Mesa, Moshe Talpaz, Jean-Jacques Kiladjian, Claire N. Harrison, Stephen T. Oh, Alessandro M. Vannucchi, Raajit Rampal, Bart L. Scott, Sarah A. Buckley, Adam R. Craig, Karisse Roman-Torres, John O. Mascarenhas

2020-Current year OA Pubs

Thrombocytopenia is common in patients with myelofibrosis (MF) and is a well-established adverse prognostic factor. Both of the approved Janus kinase (JAK) inhibitors, ruxolitinib and fedratinib, can worsen thrombocytopenia and have not been evaluated in patients with severe thrombocytopenia (platelet counts <50×109/L). Pacritinib, a novel JAK2/interleukin-1 receptor-associated kinase 1 inhibitor, has been studied in two phase III trials (PERSIST-1 and PERSIST- 2), both of which enrolled patients with MF and severe thrombocytopenia. In order to better characterize treatment outcomes for this population with advanced disease, we present a retrospective analysis of efficacy and safety data in the 189 patients with severe thrombocytopenia treated in the PERSIST studies. The proportion of patients in the pacritinib group meeting efficacy endpoints was greater than in the BAT group for ≥35% spleen volume reduction (23% vs. 2%, P=0.0007), ≥50% modified Total Symptom Score reduction (25% vs. 8%, P=0.044), and self-reported symptom benefit ("much" or "very much" improved; 25% vs. 8%, P=0.016) at the primary analysis time point (week 24). The adverse event profile of pacritinib was manageable, and dose modification was rarely required. There was no excess in bleeding or death in pacritinib-treated patients. These results indicate that pacritinib is a promising treatment for patients with MF who lack safe and effective therapeutic options due to severe thrombocytopenia.

Is Combined Surgical Dislocation And Proximal Femoral Osteotomy A Safe Procedure For Correction Of Complex Hip Deformities?, Frank W Parilla, Jeffrey J Nepple, Gail E Pashos, Perry L Schoenecker, John C Clohisy

2020-Current year OA Pubs

Complex deformities of the hip requiring intra-articular and proximal femoral correction are challenging with regard to surgical access and complication risk. Combined surgical dislocation and proximal femoral osteotomy (SD/PFO) is a surgical strategy that provides unrestricted access to the joint with the capability for adjunctive PFO. Although providing excellent surgical access, concerns over a potentially high risk of postoperative complications remain, and published information on the safety of this technique remain scarce. In this study, we defined the early complication profile of combined surgery across 48 hips with a variety of complex deformities using a standardized, validated complication grading scheme …

Community-Based Trial Assessing The Impact Of Annual Versus Semiannual Mass Drug Administration With Ivermectin Plus Albendazole And Praziquantel On Helminth Infections In Northwestern Liberia, Obiora A Eneanya, Lincoln Gankpala, Charles W Goss, Aaron T Momolu, Enoch S Nyan, Emmanuel B Gray, Kerstin Fischer, Kurt Curtis, Fatorma K Bolay, Gary J Weil, Peter U Fischer

2020-Current year OA Pubs

We assessed the impact of three annual vs five semiannual rounds of mass drug administration (MDA) with ivermectin plus albendazole followed by praziquantel for the control or elimination of lymphatic filariasis (LF), onchocerciasis, soil-transmitted helminth (STH) infections and schistosomiasis in Lofa County, Liberia. The study started in 2012 and was interrupted in 2014 during the Ebola virus outbreak. Repeated cross-sectional surveys were conducted in individuals 5 years and older to measure infection markers. Wuchereria bancrofti antigenemia prevalences decreased from 12.5 to 1.2% (90% reduction) and from 13.6 to 4.2% (69% reduction) one year after three rounds of annual or five …

Loss Of Stathmin-2, A Hallmark Of Tdp-43-Associated Als, Causes Motor Neuropathy, Kelsey L Krus, Amy Strickland, Yurie Yamada, Laura Devault, Robert E Schmidt, A Joseph Bloom, Jeffrey Milbrandt, Aaron Diantonio

2020-Current year OA Pubs

TDP-43 mediates proper Stathmin-2 (STMN2) mRNA splicing, and STMN2 protein is reduced in the spinal cord of most patients with amyotrophic lateral sclerosis (ALS). To test the hypothesis that STMN2 loss contributes to ALS pathogenesis, we generated constitutive and conditional STMN2 knockout mice. Constitutive STMN2 loss results in early-onset sensory and motor neuropathy featuring impaired motor behavior and dramatic distal neuromuscular junction (NMJ) denervation of fast-fatigable motor units, which are selectively vulnerable in ALS, without axon or motoneuron degeneration. Selective excision of STMN2 in motoneurons leads to similar NMJ pathology. STMN2 knockout heterozygous mice, which better model the partial loss …

Mrna Vaccine Boosting Enhances Antibody Responses Against Sars-Cov-2 Omicron Variant In Individuals With Antibody Deficiency Syndromes, Ofer Zimmerman, Alexa Michelle Altman Doss, Paulina Kaplonek, Chieh-Yu Liang, Laura A. Vanblargan, Rita E. Chen, Jennifer Marie Monroy, H. James Wedner, Anthony Kulczycki, Tarisa L. Mantia, Caitlin C. O'Shaughnessy, Hannah G. Davis-Adams, Harry L. Bertera, Lucas J. Adams, Saravanan Raju, Fang R. Zhao, Christopher J. Rigell, Tiffany Biason Dy, Andrew L. Kau, Zhen Ren, Jackson S. Turner, Jane A. O'Halloran, Rachel M. Presti, Daved H. Fremont, Peggy L. Kendall, Ali H. Ellebedy, Galit Alter, Michael S. Diamond

2020-Current year OA Pubs

Individuals with primary antibody deficiency (PAD) syndromes have poor humoral immune responses requiring immunoglobulin replacement therapy. We followed individuals with PAD after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination by evaluating their immunoglobulin replacement products and serum for anti-spike binding, Fcγ receptor (FcγR) binding, and neutralizing activities. The immunoglobulin replacement products tested have low anti-spike and receptor-binding domain (RBD) titers and neutralizing activity. In coronavirus disease 2019 (COVID-19)-naive individuals with PAD, anti-spike and RBD titers increase after mRNA vaccination but wane by 90 days. Those vaccinated after SARS-CoV-2 infection develop higher and more sustained responses comparable with healthy donors. …

Perceptions Of Covid-19 Self-Testing And Recommendations For Implementation And Scale-Up Among Black/African Americans: Implications For The Covid-19 Step Project, Ucheoma Nwaozuru, Thembekile Shato, Et Al.

2020-Current year OA Pubs

BACKGROUND: COVID-19 self-testing (ST) is an innovative strategy with the potential to increase the access and uptake of testing and ultimately to limit the spread of the virus. To maximize the uptake and reach of this promising strategy and inform intervention development and scale up, research is needed to understand the acceptability of and willingness to use this tool. This is vital to ensure that Black/African Americans are reached by the Biden-Harris Administration's free national COVID-19 ST program. This study aimed to explore the acceptability and recommendations to promote and scale-up the uptake of COVID-19 ST among Black/African Americans.

METHODS: …

Cryo-Em Structure Of The Prothrombin-Prothrombinase Complex, Eliza A Ruben, Brock Summers, Michael J Rau, James A J Fitzpatrick, Enrico Di Cera

2020-Current year OA Pubs

The intrinsic and extrinsic pathways of the coagulation cascade converge to a common step where the prothrombinase complex, comprising the enzyme factor Xa (fXa), the cofactor fVa, Ca2+ and phospholipids, activates the zymogen prothrombin to the protease thrombin. The reaction entails cleavage at 2 sites, R271 and R320, generating the intermediates prethrombin 2 and meizothrombin, respectively. The molecular basis of these interactions that are central to hemostasis remains elusive. We solved 2 cryogenic electron microscopy (cryo-EM) structures of the fVa-fXa complex, 1 free on nanodiscs at 5.3-Å resolution and the other bound to prothrombin at near atomic 4.1-Å resolution. In …

Csf Tau Phosphorylation At Thr205 Is Associated With Loss Of White Matter Integrity In Autosomal Dominant Alzheimer Disease, Jeremy F. Strain, Nicolas Barthelemy, Kanta Horie, Brian A. Gordon, Collin Kilgore, Andrew Aschenbrenner, Carlos Cruchaga, Chengjie Xiong, Nelly Joseph-Mathurin, Jason Hassenstab, Anne M. Fagan, Yan Li, Celeste M. Karch, Richard J. Perrin, Sarah B. Berman, Jasmeer P. Chhatwal, Neill R. Graff-Radford, Hiroshi Mori, Johannes Levin, James M. Noble, Ricardo Allegri, Peter R. Schofield, Daniel S. Marcus, David M. Holtzman, John C. Morris, Tammie L. S. Benzinger, Eric M. Mcdade, Randall J. Bateman, Beau M. Ances

2020-Current year OA Pubs

BACKGROUND: Hyperphosphorylation of tau leads to conformational changes that destabilize microtubules and hinder axonal transport in Alzheimer's disease (AD). However, it remains unknown whether white matter (WM) decline due to AD is associated with specific Tau phosphorylation site(s).

METHODS: In autosomal dominant AD (ADAD) mutation carriers (MC) and non-carriers (NC) we compared cerebrospinal fluid (CSF) phosphorylation at tau sites (pT217, pT181, pS202, and pT205) and total tau with WM measures, as derived from diffusion tensor imaging (DTI), and cognition. A WM composite metric, derived from a principal component analysis, was used to identify spatial decline seen in ADAD.

RESULTS: The …

A Dual-Center Cohort Study On The Association Between Early Deep Sedation And Clinical Outcomes In Mechanically Ventilated Patients During The Covid-19 Pandemic: The Covid-Sed Study, Robert J Stephens, Erin M Evans, Michael J Pajor, Ryan D Pappal, Haley M Egan, Max Wei, Hunter Hayes, Jason A Morris, Nicholas Becker, Brian W Roberts, Marin H Kollef, Nicholas M Mohr, Brian M Fuller

2020-Current year OA Pubs

BACKGROUND: Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes.

STUDY DESIGN AND METHODS: Dual-center, retrospective cohort study conducted over …

Indoleamine 2,3-Dioxygenase 1 Activation In Mature Cdc1 Promotes Tolerogenic Education Of Inflammatory Cdc2 Via Metabolic Communication, Marco Gargaro, Carlos G. Briseño, Prachi Bagadia, Vivek Durai, Derek J. Theisen, Sunkyung Kim, Marco Colonna, Theresa L. Murphy, Kenneth M. Murphy, Et Al.

2020-Current year OA Pubs

Conventional dendritic cells (cDCs), cDC1 and cDC2, act both to initiate immunity and maintain self-tolerance. The tryptophan metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is used by cDCs in maintaining tolerance, but its role in different subsets remains unclear. At homeostasis, only mature CCR7

Synthesizing Pseudo-T2w Images To Recapture Missing Data In Neonatal Neuroimaging With Applications In Rs-Fmri, Sydney Kaplan, Dimitrios Alexopoulos, Jeanette K Kenley, Deanna M Barch, Jeffrey J Neil, Cynthia E Rogers, Aristeidis Sotiras, Christopher D Smyser, Et Al.

2020-Current year OA Pubs

T1- and T2-weighted (T1w and T2w) images are essential for tissue classification and anatomical localization in Magnetic Resonance Imaging (MRI) analyses. However, these anatomical data can be challenging to acquire in non-sedated neonatal cohorts, which are prone to high amplitude movement and display lower tissue contrast than adults. As a result, one of these modalities may be missing or of such poor quality that they cannot be used for accurate image processing, resulting in subject loss. While recent literature attempts to overcome these issues in adult populations using synthetic imaging approaches, evaluation of the efficacy of these methods in pediatric …

Deceased Donor Procurement Biopsy Practices, Interpretation, And Histology-Based Decision-Making: A Survey Of Us Kidney Transplant Centers, Krista L. Lentine, Jason R. Wellen, Melissa Lichtenberger, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The utility of kidney procurement biopsies is controversial. Understanding the current landscape of how clinicians obtain and use biopsies in organ evaluation may help inform consensus-building efforts.

METHODS: An electronic survey was distributed to clinicians at US kidney transplant programs (April 22, 2021-June 30, 2021) to evaluate donor biopsy indications, frequency, processing and interpretation, and impact of findings on practices.

RESULTS: Responses from staff involved in organ acceptance (73% surgeons, 20% nephrologists, 6% coordinators) at 95 transplant centers were analyzed, representing 40% of US transplant centers and 50% of recent deceased donor kidney transplant volume. More than a third …

Low Housing Quality, Unmet Social Needs, Stress And Depression Among Low-Income Smokers, Rachel Garg, Amy Mcqueen, Jennifer M Wolff, Karen E Skinner, Michelle C Kegler, Matthew W Kreuter

2020-Current year OA Pubs

Smokers are at greater risk of multiple health conditions that are exacerbated by environmental hazards associated with low housing quality. However, little is known about the prevalence of low housing quality among low-income smokers. Using correlations and logistic regression, we examined associations among eight housing quality indicators - pests, water leaks, mold, lead paint, and working smoke detectors, appliances, heating, and air conditioning - and between housing quality and social needs, depressive symptoms, perceived stress, sleep problems, and self-rated health in a community-based sample of 786 low-income smokers from 6 states. Most participants were female (68%), and White (45%) or …

Escape-Noncapture Bigeminy, Lisa M. Roelle, George F. Van Hare

2020-Current year OA Pubs

No abstract provided.

22q11.2 Deletion Syndrome - A Series Of Patients With Midline Skull Base Defects, Spencer S. Souza, Lia Jacobson, Dylan Chan, Anna Meyer, Jarod L. Roland, Kimberly Luu

2020-Current year OA Pubs

No abstract provided.

Management Of Diarrhea In Patients With Her2-Positive Breast Cancer Treated With Neratinib: A Case Series And Summary Of The Literature, Megan L Kruse, Irene M Kang, Nusayba A Bagegni, W Todd Howell, Halle C F Moore, Cynthia H Bedell, Christopher T Stokoe

2020-Current year OA Pubs

INTRODUCTION: Neratinib and neratinib-based combinations have demonstrated efficacy for treatment of human epidermal growth factor receptor 2-positive (HER2+) early-stage and metastatic breast cancers. However, diarrhea has been reported as a common adverse event leading to neratinib discontinuation. Results from the CONTROL trial suggest that proactive diarrhea management with antidiarrheal prophylaxis or dose escalation of neratinib from a lower starting dose to the full FDA-approved dose of 240 mg/day can reduce the incidence, duration, and severity of neratinib-associated diarrhea in patients with early-stage breast cancer. Dose escalation has been included in the FDA-approved label for both early-stage and metastatic HER2+ breast …

Intracorporeal And Extracorporeal Anastomosis For Robotic-Assisted And Laparoscopic Right Colectomy: Short-Term Outcomes Of A Multi-Center Prospective Trial, Robert K Cleary, Matthew Silviera, Et Al.

2020-Current year OA Pubs

BACKGROUND: Studies to date show contrasting conclusions when comparing intracorporeal and extracorporeal anastomoses for minimally invasive right colectomy. Large multi-center prospective studies comparing perioperative outcomes between these two techniques are needed. The purpose of this study was to compare intracorporeal and extracorporeal anastomoses outcomes for robotic assisted and laparoscopic right colectomy.

METHODS: Multi-center, prospective, observational study of patients with malignant or benign disease scheduled for laparoscopic or robotic-assisted right colectomy. Outcomes included conversion rate, gastrointestinal recovery, and complication rates.

RESULTS: There were 280 patients: 156 in the robotic assisted and laparoscopic intracorporeal anastomosis (IA) group and 124 in the robotic …

A Short-Term Multicenter Analysis Of Radiolucent Lines In A Single Uncemented Rotating Platform Implant For Total Knee Arthroplasty, Jason Desmarais, David Dalury, Thomas L. Bernasek, David A. Fisher, Ryan M. Nunley, Marie-Claire Fickenscher, Robert S Gorab

2020-Current year OA Pubs

BACKGROUND: Uncemented total knee arthroplasty is increasing as a potential solution for aseptic loosening via biologic fixation and to increase operative efficiency. However, postoperative radiolucent lines (RLLs) remain a concern for some clinicians. We report on a multicenter analysis of these RLLs over a 2-year period to identify their incidence, progression, and clinical significance.

MATERIAL AND METHODS: Institutional review board approval was obtained for this retrospective, multicenter case series. A total of 312 patients treated with a single cruciate-retaining, fully porous coated femoral and tibial component design were included in the study. All patients were evaluated clinically and radiographically in …

Real-Time Motion Monitoring Improves Functional Mri Data Quality In Infants, Carolina Badke D'Andrea, Jeanette K Kenley, David F Montez, Amy E Mirro, Ryland L Miller, Eric A Earl, Jonathan M Koller, Sooyeon Sung, Essa Yacoub, Jed T Elison, Damien A Fair, Nico U F Dosenbach, Cynthia E Rogers, Christopher D Smyser, Deanna J Greene

2020-Current year OA Pubs

Imaging the infant brain with MRI has improved our understanding of early neurodevelopment. However, head motion during MRI acquisition is detrimental to both functional and structural MRI scan quality. Though infants are typically scanned while asleep, they commonly exhibit motion during scanning causing data loss. Our group has shown that providing MRI technicians with real-time motion estimates via Framewise Integrated Real-Time MRI Monitoring (FIRMM) software helps obtain high-quality, low motion fMRI data. By estimating head motion in real time and displaying motion metrics to the MR technician during an fMRI scan, FIRMM can improve scanning efficiency. Here, we compared average …

Age-Dependent White Matter Disruptions After Military Traumatic Brain Injury: Multivariate Analysis Results From Enigma Brain Injury, Heather C Bouchard, Paul M Thompson, Aristeidis Sotiras, Et Al.

2020-Current year OA Pubs

Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age-related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non-negative matrix factorization (NMF) is a data-driven approach that detects covarying patterns (components) within high-dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self-reported TBI history. NMF identified 12 independent components derived from fractional …

Phase I Trial Of Atm Inhibitor M3541 In Combination With Palliative Radiotherapy In Patients With Solid Tumors, Saiama N Waqar, Clifford Robinson, Anthony J Olszanski, Alexander Spira, Melissa Hackmaster, Luisa Lucas, Laura Sponton, Hulin Jin, Ursula Hering, Damien Cronier, Marianna Grinberg, Annick Seithel-Keuth, Ivan Diaz-Padilla, Jordan Berlin

2020-Current year OA Pubs

BACKGROUND: Ataxia telangiectasia mutated (ATM) kinase orchestrates DNA double strand break (DSB) repair; ATM inhibitors may therefore enhance the therapeutic effect of DSB-inducing treatments such as radiotherapy (RT). M3541 is an orally administered selective inhibitor of ATM.

METHODS: This phase I dose-escalation study evaluated the maximum-tolerated dose (MTD), recommended phase II dose(s) (RP2D), safety, pharmacokinetics (PK) and antitumor activity of M3541 in combination with fractionated palliative RT in patients with solid tumors. Fifteen patients received palliative RT (30 Gy in 10 fractions) and escalating doses of M3541 (50-300 mg administered on RT fraction days) guided by a Bayesian 2-parameter logistic …

A Single-Center Experience Comparing First- Versus Second-Generation Insertable Cardiac Monitors In Pediatric Patients, Nathan Miller, Lisa Roelle, Dean Lorimer Jr, Aarti S Dalal, William B Orr, George F Van Hare, Jennifer N Avari Silva

2020-Current year OA Pubs

Insertable cardiac monitors (ICMs) have undergone advancements in size and functionality over the past decade, resulting in the introduction of small, easily insertable devices capable of long-term remote monitoring. We define first-generation ICMs as implantable cardiac monitoring devices that require an incision and surgical creation of a subcutaneous pocket and second-generation ICMs as devices implanted using a custom-made tool for subcutaneous insertion, respectively. The aim of this study was to understand the differences between first- and second-generation pediatric ICM implants, implant indications, and time to diagnosis. We performed a retrospective, single-center chart review of patients who underwent ICM implantation from …