Digital Commons Network^™

Sars-Cov-2 Reverse Genetics Reveals A Variable Infection Gradient In The Respiratory Tract, Yixuan J. Hou, Kenichi Okuda, Caitlin E. Edwards, David R. Martinez, Takanori Asakura, Kenneth H. Dinnon, Takafumi Kato, Rhianna E. Lee, Boyd L. Yount, Teresa M. Mascenik, Gang Chen, Kenneth N. Olivier, Andrew Ghio, Longping V. Tse, Sarah R. Leist, Lisa E. Gralinski, Alexandra Schäfer, Hong Dang, Rodney Gilmore, Satoko Nakano, Ling Sun, M Leslie Fulcher, Alessandra Livraghi-Butrico, Nathan I. Nicely, Mark Cameron, Cheryl Cameron, David J. Kelvin, Aravinda De Silva, David M. Margolis, Alena Markmann, Luther Bartelt, Ross Zumwalt, Fernando J. Martinez, Steven P. Salvatore, Alain Borczuk, Purushothama R. Tata, Vishwaraj Sontake, Adam Kimple, Ilona Jaspers, Wanda K. O'Neal, Scott H. Randell, Richard C. Boucher, Ralph S. Baric

Pathology Research and Scholarship

The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 …

Trial Of Roflumilast Cream For Chronic Plaque Psoriasis, Mark G. Lebwohl, Kim A. Papp, Linda F. Stein Gold, Melinda J. Gooderham, Leon H. Kircik, Zoe D. Draelos, Steven E. Kempers, Mathew Zirwas, Kathleen Smith, David W. Osborne, Marie-Louise Trotman, Lynn Navale, Charlotte Merritt, David R. Berk, Howard Welgus

Dermatology Articles

BACKGROUND: Systemic oral phosphodiesterase type 4 (PDE-4) inhibitors have been effective in the treatment of psoriasis. Roflumilast cream contains a PDE-4 inhibitor that is being investigated for the topical treatment of psoriasis.

METHODS: In this phase 2b, double-blind trial, we randomly assigned adults with plaque psoriasis in a 1:1:1 ratio to use roflumilast 0.3% cream, roflumilast 0.15% cream, or vehicle (placebo) cream once daily for 12 weeks. The primary efficacy outcome was the investigator's global assessment (IGA) of a status of clear or almost clear at week 6 (assessed on a 5-point scale of plaque thickening, scaling, and erythema; a …

The Influence Of Telehealth For Better Health Across Communities., Jane A. Mcelroy, Tamara M. Day, Mirna Becevic

Project ECHO Bibliography

Rapid spread of coronavirus disease 2019 (COVID-19) forced an abrupt shift in the traditional US health care delivery model to meet the needs of patients, staff, and communities. Through federal policy changes on telehealth, patient care shifted from in-person to telephone or video visits, and health care providers reached out to patients most at risk for exacerbation of chronic disease symptoms. ECHO (Extension for Community Healthcare Outcomes), a videoconferencing peer learning application, engaged health care providers across Missouri in the treatment and management of complex COVID-19-positive patients. Re-envisioning health care in the digital age includes robust utilization of telehealth to …

Molecular And Clinicopathologic Features Of Gliomas Harboring Ntrk Fusions, Matthew Torre, Sonika Dahiya, Et Al

Open Access Publications

Fusions involving neurotrophic tyrosine receptor kinase (NTRK) genes are detected in ≤2% of gliomas and can promote gliomagenesis. The remarkable therapeutic efficacy of TRK inhibitors, which are among the first Food and Drug Administration-approved targeted therapies for NTRK-fused gliomas, has generated significant clinical interest in characterizing these tumors. In this multi-institutional retrospective study of 42 gliomas with NTRK fusions, next generation DNA sequencing (n = 41), next generation RNA sequencing (n = 1), RNA-sequencing fusion panel (n = 16), methylation profile analysis (n = 18), and histologic evaluation (n = 42) were performed. All infantile NTRK-fused gliomas (n = 7) …

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities In Lung Adenocarcinoma, Michael A. Gillette, Song Cao, Yize Li, Wen-Wei Liang, Michael C Wendl, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. …

Comparison Of Tissue Molecular Biomarker Testing Turnaround Times And Concordance Between Standard Of Care And The Biocartis Idylla Platform In Patients With Colorectal Cancer, Gregory J. Tsongalis, M Rabie Al Turkmani, Michael Suriawinata, Michael J. Babcock, Kristi Mitchell, Yi Ding, Lisa Scicchitano, Adrian Tira, Lela Buckingham, Sara Atkinson, Amy Lax, Dara L. Aisner, Kurtis D. Davies, Holly N. Wood, Stacey S. O'Neill, Edward A. Levine, Judy Sequeira, Shuko Harada, Gina Defrank, Ravikumar Paluri, Bradford A. Tan, Heather Colabella, Christopher Snead, Marcia Cruz-Correa, Virginia Ramirez, Arnaldo Rojas, Huiya Huang, Alexander C. Mackinnon, Fernando U. Garcia, Sharon M. Cavone, Mutasim Elfahal, Gyorgy Abel, Mohammad A. Vasef, Andrew Judd, Mark W. Linder, Khaled Alkhateeb, William L. Skinner, Ralph Boccia, Kashyap Patel

Pathology Research and Scholarship

OBJECTIVES: Management of colorectal cancer warrants mutational analysis of KRAS/NRAS when considering anti-epidermal growth factor receptor therapy and BRAF testing for prognostic stratification. In this multicenter study, we compared a fully integrated, cartridge-based system to standard-of-care assays used by participating laboratories.

METHODS: Twenty laboratories enrolled 874 colorectal cancer cases between November 2017 and December 2018. Testing was performed on the Idylla automated system (Biocartis) using the KRAS and NRAS-BRAF cartridges (research use only) and results compared with in-house standard-of-care testing methods.

RESULTS: There were sufficient data on 780 cases to measure turnaround time compared with standard assays. In-house polymerase chain …

Metformin Enhances Autophagy And Normalizes Mitochondrial Function To Alleviate Aging-Associated Inflammation, Leena P Bharath, Madhur Agrawal, Grace Mccambridge, Dequina A Nicholas, Hatice Hasturk, Jing Liu, Kai Jiang, Rui Liu, Zhenheng Guo, Jude Deeney, Caroline M Apovian, Jennifer Snyder-Cappione, Gregory S Hawk, Rebecca M Fleeman, Riley M F Pihl, Katherine Thompson, Anna C Belkina, Licong Cui, Elizabeth A Proctor, Philip A Kern, Barbara S Nikolajczyk

Faculty, Staff and Student Publications

Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 …

Screening And Treatment Outcomes In Adults And Children With Type 1 Diabetes And Asymptomatic Celiac Disease: The Cd-Diet Study., Farid H Mahmud, Antoine B M Clarke, Kariym C Joachim, Esther Assor, Charlotte Mcdonald, Fred Saibil, Heather A Lochnan, Zubin Punthakee, Amish Parikh, Andrew Advani, Baiju R Shah, Bruce A Perkins, Caroline S Zuijdwijk, David R Mack, Dror Koltin, Emilia N De Melo, Eugene Hsieh, Geetha Mukerji, Jeremy Gilbert, Kevin Bax, Margaret L Lawson, Maria Cino, Melanie D Beaton, Navaaz A Saloojee, Olivia Lou, Patricia H Gallego, Premysl Bercik, Robyn L Houlden, Ronnie Aronson, Susan E Kirsch, William G Paterson, Margaret A Marcon

Paediatrics Publications

OBJECTIVE: To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD.

RESEARCH DESIGN AND METHODS: Asymptomatic patients (8-45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA

RESULTS: Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9-8.2%,

CONCLUSIONS: CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.

A Foldable Nonpenetrating Keratoprosthesis: Medium To Long-Term Clinical Results In Patients With Corneal Blindness Due To Noninflammatory Anterior Cornea Disease., Jose M Vargas, Eric Shiuey

Department of Medicine Faculty Papers

PURPOSE: To report the medium to long-term safety and performance outcomes of the KeraKlear nonpenetrating artificial cornea (KeraKlear) as the primary procedure in patients with corneal blindness due to noninflammatory anterior cornea disease.

METHODS: Fifteen patients with corneal blindness (preoperative visual acuity [VA] of ≥20/200) due to a non-inflammatory anterior corneal condition were included in this prospective, single-center study. Preoperative diagnoses included corneal scars, keratoconus, and corneal dystrophies. Diseased corneas were implanted with the KeraKlear (KeraMed Inc., Irvine, California, USA) by a single surgeon (JMV) using a femtosecond laser to create all incisions. Participants were followed up with for as …

Development Of The Uncertainty Communication Checklist: A Patient-Centered Approach To Patient Discharge From The Emergency Department, Kristin L. Rising, Rhea E. Powell, Kenzie A Cameron, David H Salzman, Dimitrios Papanagnou, Amanda Doty, Lori Latimer, Katherine Piserchia, William C Mcgaghie, Danielle M Mccarthy

Department of Emergency Medicine Faculty Papers

Clear communication with patients upon emergency department (ED) discharge is important for patient safety during the transition to outpatient care. Over one-third of patients are discharged from the ED with diagnostic uncertainty, yet there is no established approach for effective discharge communication in this scenario. From 2017 to 2019, the authors developed the Uncertainty Communication Checklist for use in simulation-based training and assessment of emergency physician communication skills when discharging patients with diagnostic uncertainty. This development process followed the established 12-step Checklist Development Checklist framework and integrated patient feedback into 6 of the 12 steps. Patient input was included as …

Physiological Factors Of Female Runners With And Without Stress Fracture Histories: A Pilot Study., Therese E Johnston, Colleen Dempsey, Frances Gilman, Ryan Tomlinson, Ann-Katrin Jacketti, Jeremy Close

Department of Physical Therapy Faculty Papers

BACKGROUND: Female runners are at increased risk of stress fractures (SFs) compared with men. Literature is lacking with regard to best practice for preventing and treating SFs in women. The purpose of the study was to compare physiological measures and running-related factors between women of various ages and running abilities with and without a history of running-related SFs.

HYPOTHESIS: Women with and without SF histories will differ with regard to medical and menstrual history, bone health, body composition, nutrition, and running history.

STUDY DESIGN: Prospective cohort study.

LEVEL OF EVIDENCE: Level 2.

METHODS: A total of 20 female runners with …

Association Of Interleukin 7 Immunotherapy With Lymphocyte Counts Among Patients With Severe Coronavirus Disease 2019 (Covid-19), Pierre Francois Laterre, Bruno François, Christine Collienne, Philippe Hantson, Robin Jeannet, Kenneth E. Remy, Richard S. Hotchkiss

Open Access Publications

No abstract provided.

Association Analysis Of Driver Gene-Related Genetic Variants Identified Novel Lung Cancer Susceptibility Loci With 20,871 Lung Cancer Cases And 15,971 Controls, Yuzhuo Wang, Olga Y Gorlova, Ivan P Gorlov, Meng Zhu, Juncheng Dai, Demetrius Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Gary E Goodman, Stig E Bojesen, Maria Teresa Landi, Mattias Johansson, Angela Risch, Heunz-Erich Wichmann, Heike Bickeboller, David C Christiani, Gad Rennert, Susanne M Arnold, Paul Brennan, John K Field, Sanjay Shete, Loïc Le Marchand, Olle Melander, Hans Brunnstrom, Geoffrey Liu, Rayjean J Hung, Angeline S Andrew, Lambertus A Kiemeney, Shanbeh Zienolddiny, Kjell Grankvist, Mikael Johansson, Neil E Caporaso, Penella J Woll, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Victoria L Stevens, Hongxia Ma, Guangfu Jin, Zhibin Hu, Christopher I Amos, Hongbing Shen

Faculty, Staff and Students Publications

BACKGROUND: A substantial proportion of cancer driver genes (CDG) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated.

METHODS: We selected expression-related single-nucleotide polymorphisms (eSNP) and nonsynonymous variants of lung CDGs, and tested their associations with lung cancer risk in two large-scale genome-wide association studies (20,871 cases and 15,971 controls of European descent). Conditional and joint association analysis was performed to identify independent risk variants. The associations of independent risk variants with somatic alterations in lung CDGs or recurrently altered pathways were investigated using data …

Impact Of Vancomycin-Induced Changes In The Intestinal Microbiota On The Pharmacokinetics Of Simvastatin, Jung Sunwoo, Sang Chun Ji, Andrew Hyoungjin Kim, Kyung-Sang Yu, Joo-Youn Cho, In-Jin Jang, Seunghwan Lee

2020-Current year OA Pubs

The pharmacokinetic (PK) properties of drugs are affected in several ways by interactions with microbiota. The aim of this study was to investigate the effects of oral vancomycin on the gut microbiota and, consequently, on the PKs of simvastatin. An open-label, single arm, sequential crossover study was conducted in six healthy Korean male subjects. After 6 days on a control diet, simvastatin 40 mg was orally administered to the subjects before and after 1 week of oral vancomycin treatment. Blood samples for PK analysis and fecal samples for metagenomic and metabolomic analyses were collected. After vancomycin treatment, the richness of …

Combined Lenvatinib And Pembrolizumab As Salvage Therapy In Advanced Adrenal Cortical Carcinoma, Sara Bedrose, Kevin Charles Miller, Lina Altameemi, Mohamed S Ali, Sameh Nassar, Naveen Garg, Marilyne Daher, Keith D Eaton, Jeffrey Thomas Yorio, Davey B Daniel, Matthew Campbell, Keith C Bible, Mabel Ryder, Ashish V Chintakuntlawar, Mouhammed Amir Habra

Faculty, Staff and Students Publications

BACKGROUND: There is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC.

METHODS: A retrospective case series describing the use of LEN/PEM …

A Domain-General Cognitive Core Defined In Multimodally Parcellated Human Cortex, Moataz Assem, Matthew F Glasser, David C Van Essen, John Duncan

2020-Current year OA Pubs

Numerous brain imaging studies identified a domain-general or "multiple-demand" (MD) activation pattern accompanying many tasks and may play a core role in cognitive control. Though this finding is well established, the limited spatial localization provided by traditional imaging methods precluded a consensus regarding the precise anatomy, functional differentiation, and connectivity of the MD system. To address these limitations, we used data from 449 subjects from the Human Connectome Project, with the cortex of each individual parcellated using neurobiologically grounded multimodal MRI features. The conjunction of three cognitive contrasts reveals a core of 10 widely distributed MD parcels per hemisphere that …

Prevalence, Incidence, And Clearance Of Human Papillomavirus Types Covered By Current Vaccines In Men With Human Immunodeficiency Virus In The Sun Study, Pragna Patel, Tim Bush, Lois Conley, Elizabeth R Unger, Teresa M Darragh, Keith Henry, Gerome Escota, John T Brooks, Erna Milunka Kojic

2020-Current year OA Pubs

BACKGROUND: High-risk anal human papillomavirus (HPV) infection is prevalent among men living with human immunodeficiency virus (HIV); the association between 9-valent (9v) high-risk HPV (HR-HPV) vaccine types and abnormal cytology has not been well characterized.

METHODS: We followed a prospective cohort study of persons with HIV at 7 HIV clinics in 4 US cities from March 2004 through June 2012. Annually, providers collected separate anal swabs for HPV detection and cytopathologic examination. Among men, we examined prevalence, incidence, and clearance of 9v HR-HPV vaccine types, compared with other HR types, and associations with abnormal cytology to assess potential vaccine impact. …

Vitamin A And Fish Oils For Preventing The Progression Of Retinitis Pigmentosa., Stephen G. Schwartz, Xue Wang, Pamela Chavis, Ajay E. Kuriyan, Samuel A. Abariga

Wills Eye Hospital Papers

BACKGROUND: Retinitis pigmentosa (RP) comprises a group of hereditary eye diseases characterized by progressive degeneration of retinal photoreceptors. It results in severe visual loss that may lead to blindness. Symptoms may become manifest during childhood or adulthood which include poor night vision (nyctalopia) and constriction of peripheral vision (visual field loss). Visual field loss is progressive and affects central vision later in the disease course. The worldwide prevalence of RP is approximately 1 in 4000, with 100,000 individuals affected in the USA. At this time, there is no proven therapy for RP.

OBJECTIVES: The objective of this review was to …

Highlights Of Studies In Cardiovascular Disease Prevention Presented At The 2020 American College Of Cardiology Annual Scientific Session, Xiaoming Jia, Mahmoud Al Rifai, Jing Liu, Anandita Agarwala, Martha Gulati, Salim S Virani

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: The review highlights selected studies related to cardiovascular disease (CVD) prevention that were presented at the American College of Cardiology 2020 Virtual Scientific Session (ACC.20)/World Cardiology Congress (WCC).

RECENT FINDINGS: The studies reviewed include clinical trials on the efficacy and safety of alirocumab (Study in Participants with Homozygous Familial Hypercholesterolemia [ODYSSEY HoFH]) and evinacumab in the treatment of homozygous familial hypercholesterolemia (HoFH); Evaluating the Efficacy of E-cigarettes for Smoking Cessation (E3); the use of renal denervation in the treatment of hypertension (SPYRAL HTN-OFF MED PIVOTAL); and the assessment of vericiguat in the treatment of heart failure (A …

Effect Of Continuous Glucose Monitoring On Hypoglycemia In Older Adults With Type 1 Diabetes: A Randomized Clinical Trial, Richard E. Pratley, Lauren G. Kanapka, Michael R. Rickels, Andrew Ahmann, Grazia Aleppo, Roy Beck, Anuj Bhargava, Bruce W. Bode, Anders Carlson, Naomi S. Chaytor, D Steven Fox, Robin Goland, Irl B. Hirsch, Davida F. Kruger, Yogish C. Kudva, Carol Levy, Janet B. Mcgill, Anne Peters, Louis Philipson, Athena Philis-Tsimikas, Rodica Pop-Busui, Viral N. Shah, Michael Thompson, Francesco Vendrame, Alandra Verdejo, Ruth S. Weinstock, Laura Young, Kellee M. Miller

Endocrinology Articles

Importance: Continuous glucose monitoring (CGM) provides real-time assessment of glucose levels and may be beneficial in reducing hypoglycemia in older adults with type 1 diabetes.

Objective: To determine whether CGM is effective in reducing hypoglycemia compared with standard blood glucose monitoring (BGM) in older adults with type 1 diabetes.

Design, Setting, and Participants: Randomized clinical trial conducted at 22 endocrinology practices in the United States among 203 adults at least 60 years of age with type 1 diabetes.

Interventions: Participants were randomly assigned in a 1:1 ratio to use CGM (n = 103) or standard BGM (n = 100).

Main …

A Genome-Wide Association Study Identifies Two Novel Susceptible Regions For Squamous Cell Carcinoma Of The Head And Neck, Sanjay Shete, Hongliang Liu, Jian Wang, Robert Yu, Erich M Sturgis, Guojun Li, Kristina R Dahlstrom, Zhensheng Liu, Christopher I Amos, Qingyi Wei

Faculty, Staff and Students Publications

To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which 434,839 typed and 7,423,250 imputed SNPs as the discovery. SNPs with P <1×10–3 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from dbGaP. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 (P = 2.96×10–9 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, HLA-DQB1) and 6p21.33 (rs1265081, CCHCR1) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 (P = 2.54×10–9 for the leading SNP rs142021700) was identified for hypo-pharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and eQTL analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of HLA loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN.

Association Between Changes In Subjective And Objective Measures Of Mobility In People With Lower Limb Amputations After Inpatient Rehabilitation, Gabrielle Cieslak, Humberto Omana, Edward Madou, Courtney Frengopoulos, Ricardo Viana, Michael W Payne, Susan W. Hunter

Physical Therapy Publications

Functional recovery for people with lower limb amputations is quantified using objective or subjective measures of performance. In this brief report, the prospective relationship between objective and subjective mobility after rehabilitation was evaluated in people with lower limb amputations. Adults undergoing inpatient prosthetic rehabilitation for a first unilateral transtibial or transfemoral level lower limb amputation were recruited. Assessment times: discharge and 4-mo follow-up. Gait velocity and the L Test under single- and dual-task conditions measured objective mobility. The Prosthetic Evaluation Questionnaire (section 4 and question 5b) measured subjective mobility. Paired t tests and Pearson correlation analysis evaluated change over time …

Fri0547 The Effect Of Corrected Inflammation, Oxidative Stress And Endothelial Dysfunction On Fmd Levels In Patients With Selected Chronic Diseases: A Quasi-Experimental Study., Mahmut Ilker Yilmaz, Micol Romano, Mustafa Kemal Basarali, Abdelbaset Elzagallaai, Murat Karaman, Zeynep Demir, Muhammet Fatih Demir, Fatih Akcay, Melik Seyrek, Nuri Haksever, David Piskin, Rolando Cimaz, Michael Rieder, Erkan Demirkaya

Paediatrics Publications

While the pathophysiology of chronic disorders varies there are three basic mechanisms - inflammation, oxidative stress and endothelial dysfunction - that are common in many chronic diseases. However, the failure of these mechanisms to work synchronously can lead to morbidity complicating the course of many chronic diseases. We analyzed data of 178 patients from cohorts with selected chronic diseases in this quasi-experimental study. Endothelial dysfunction was determined by flow-mediated dilatation (FMD) and asymmetric dimethylarginine (ADMA) levels. Serum ADMA, high sensitive C-reactive protein (hs-CRP), serum PTX3, malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels and FMD were studied in baseline …

The Effect Of Corrected Inflammation, Oxidative Stress And Endothelial Dysfunction On Fmd Levels In Patients With Selected Chronic Diseases: A Quasi-Experimental Study., Mahmut Ilker Yilmaz, Micol Romano, Mustafa Kemal Basarali, Abdelbaset Elzagallaai, Murat Karaman, Zeynep Demir, Muhammet Fatih Demir, Fatih Akcay, Melik Seyrek, Nuri Haksever, David Piskin, Rolando Cimaz, Michael Rieder, Erkan Demirkaya

Paediatrics Publications

While the pathophysiology of chronic disorders varies there are three basic mechanisms - inflammation, oxidative stress and endothelial dysfunction - that are common in many chronic diseases. However, the failure of these mechanisms to work synchronously can lead to morbidity complicating the course of many chronic diseases. We analyzed data of 178 patients from cohorts with selected chronic diseases in this quasi-experimental study. Endothelial dysfunction was determined by flow-mediated dilatation (FMD) and asymmetric dimethylarginine (ADMA) levels. Serum ADMA, high sensitive C-reactive protein (hs-CRP), serum PTX3, malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels and FMD were studied in baseline …

Evaluation Of Mavacamten In Symptomatic Patients With Nonobstructive Hypertrophic Cardiomyopathy, Carolyn Y Ho, Richard G Bach, Et Al.

2020-Current year OA Pubs

BACKGROUND: Patients with nonobstructive hypertrophic cardiomyopathy (nHCM) often experience a high burden of symptoms; however, there are no proven pharmacological therapies. By altering the contractile mechanics of the cardiomyocyte, myosin inhibitors have the potential to modify pathophysiology and improve symptoms associated with HCM.

OBJECTIVES: MAVERICK-HCM (Mavacamten in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy) explored the safety and efficacy of mavacamten, a first-in-class reversible inhibitor of cardiac-specific myosin, in nHCM.

METHODS: The MAVERICK-HCM trial was a multicenter, double-blind, placebo-controlled, dose-ranging phase II study in adults with symptomatic nHCM (New York Heart Association functional class II/III), left ventricular ejection fraction (LVEF) ≥55%, …

Randomized Controlled Trial Of A Multilevel Intervention To Address Social Determinants Of Refugee Mental Health, Jessica R. Goodkind, Deborah Bybee, Julia Meredith Hess, Suha Amer, Martin Ndayisenga, R Neil Greene, Ryeora Choe, Brian Isakson, Brandon Baca, Mahbooba Pannah

Pediatrics Research and Scholarship

Understanding processes that support the well-being of the unprecedented numbers of forcibly displaced people throughout the world is essential. Growing evidence documents post-migration stressors related to marginalization as key social determinants of refugee mental health. The goal of this RCT was to rigorously test a social justice approach to reducing high rates of distress among refugees in the United States. The 6-month multilevel, strengths-based Refugee Well-being Project (RWP) intervention brought together university students enrolled in a 2-semester course and recently resettled refugees to engage in mutual learning and collaborative efforts to mobilize community resources and improve community and systems responsiveness …

Viscoelastic Testing In Covid-19: A Possible Screening Tool For Severe Disease, Jay S. Raval, Allison E. Burnett, Marian A. Rollins-Raval, Joseph R. Griggs, Lizabeth Rosenbaum, Nathan D. Nielsen, Michelle S. Harkins

Pathology Research and Scholarship

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) that manifests with variable severity. 1 A subset of symptomatic individuals develop proinflammatory or prothrombotic profiles requiring additional testing and interventions. 2-5 It is unclear which COVID-19 patients will ultimately develop severe disease that would have benefitted from early and aggressive interventions.

Traumatic Injury Results In Prolonged Circulation Of Ultralarge Von Willebrand Factor And A Reduction In Adamts13 Activity, Mitchell R. Dyer, William E. Plautz, Margaret V. Ragni, Wyeth Alexander, Shannon Haldeman, Jason L. Sperry, Francis X. Guyette, Brian S. Zuckerbraun, Marian A. Rollins-Raval, Jay S. Raval, Matthew D. Neal

Pathology Research and Scholarship

BACKGROUND: Increases in plasma von Willebrand Factor (VWF) levels, accompanied by decreases in the metalloprotease ADAMTS13, have been demonstrated soon after traumatic injury while downstream effects remain unclear.

STUDY DESIGN AND METHODS: A cohort of 37 injured trauma patients from a randomized control trial investigating the use of prehospital plasma transfusion were analyzed for activity and antigen levels of ADAMTS13 and VWF at 0 and 24 hours after admission. Relevant clinical data were abstracted from the medical records. Trauma patient plasma was analyzed via agarose gel electrophoresis to evaluate the effects of injury on VWF multimer composition compared to healthy …

Relationships Of P16 Immunohistochemistry And Other Biomarkers With Diagnoses Of Cervical Abnormalities: Implications For Last Terminology, Philip E. Castle, Rachael Adcock, Jack Cuzick, Nicolas Wentzensen, Norah E. Torrez-Martinez, Salina M. Torres, Mark H. Stoler, Brigitte M. Ronnett, Nancy E. Joste, Teresa M. Darragh, Patti E. Gravitt, Mark Schiffman, William C. Hunt, Walter K. Kinney, Cosette M. Wheeler

Pathology Research and Scholarship

CONTEXT.—: Lower Anogenital Squamous Terminology (LAST) standardization recommended p16

OBJECTIVE.—: To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses.

DESIGN.—: A statewide, stratified sample of cervical biopsies diagnosed by community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available.

RESULTS.—: Biopsies were more likely to test p16 IHC positive with increasing severity of CP …

Bosutinib For Pretreated Patients With Chronic Phase Chronic Myeloid Leukemia: Primary Results Of The Phase 4 Byond Study, Andreas Hochhaus, Camille Abboud, Et Al

Open Access Publications

Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of …