Medicine and Health Sciences Commons^™

First-In-Human Phase I/Ib Study Of Niz985, A Recombinant Heterodimer Of Il-15 And Il-15rα, As A Single Agent And In Combination With Spartalizumab In Patients With Advanced And Metastatic Solid Tumors, Rom Leidner, Kevin Conlon, Douglas G Mcneel, Andrea Wang-Gillam, Sumati Gupta, Robert Wesolowski, Monica Chaudhari, Nadia Hassounah, Jong Bong Lee, Lang Ho Lee, Jessica A O'Keeffe, Nancy Lewis, George N Pavlakis, John A Thompson

2020-Current year OA Pubs

BACKGROUND: Preclinically, interleukin-15 (IL-15) monotherapy promotes antitumor immune responses, which are enhanced when IL-15 is used in combination with immune checkpoint inhibitors (ICIs). This first-in-human study investigated NIZ985, a recombinant heterodimer comprising physiologically active IL-15 and IL-15 receptor α, as monotherapy and in combination with spartalizumab, an anti-programmed cell death protein-1 (anti-PD-1) monoclonal antibody, in patients with advanced solid tumors.

METHODS: This phase I/Ib study had two dose-escalation arms: single-agent NIZ985 administered subcutaneously thrice weekly (TIW, 2 weeks on/2 weeks off) or once weekly (QW, 3 weeks on/1 week off), and NIZ985 TIW or QW administered subcutaneously plus spartalizumab (400 …

Difelikefalin Suppresses Itch And Reduces Scratching Independent Of Inflammation In A Murine Model Of Atopic Dermatitis, Masato Tamari, Lydia Zamidar, Aaron M Ver Heul, Kristine Nograles, Joana Goncalves, Emma Guttman-Yassky, Mark Lebwohl, Brian S Kim

2020-Current year OA Pubs

BACKGROUND: Therapies specifically targeting nonhistaminergic pruritus are largely lacking. Difelikefalin (DFK) has been found to reduce itch in various chronic pruritic conditions, including atopic dermatitis (AD).

OBJECTIVE: We sought to investigate the ability of DFK to impact scratching behavior, inflammatory mediators, and neuronal signaling in a murine model of AD.

METHODS: The ears of C57BL/6 mice were topically treated with MC903 for 12 consecutive days to induce AD-like inflammation and itch. Before MC903 treatment, mice were treated with either DFK (0.5 mg/kg, intraperitoneal injection twice daily) or vehicle (saline). Skin ear thickness, histological analysis, flow cytometry, RNA-sequencing, and differential gene …

Management Of Severe Tricuspid Valve Regurgitation Due To Ruptured Papillary Muscle In A Patient With Mediastinitis Early After Heart Transplant, Erin M Schumer, Kunal D Kotkar, M Faraz Masood, Tsuyoshi Kaneko, Ralph J Damiano, Amit Pawale

2020-Current year OA Pubs

OBJECTIVE: Even though severe tricuspid regurgitation is not uncommon after cardiac transplantation, primary severe tricuspid regurgitation is rare. We present such a case with additional complexities.

METHODS: The patient was 44-year-old man with a HeartWare durable left ventricular assist device (Heartware Inc) who received a temporary right ventricular assist device (RVAD) with a ProtekDuo cannula (LivaNova Inc USA) for refractory ventricular fibrillation and underwent a heart transplant as United Network for Organ Sharing Status 1, in the presence of partially compensated cardiogenic shock, renal failure. Given complex re-operative surgery in a volume-overloaded patient with unknown pulmonary vascular resistance, an RVAD …

Clinical Classification Of Variants In The Valosin-Containing Protein Gene Associated With Multisystem Proteinopathy, Marianela Schiava, Jil Daw, Conrad Chris Weihl, Et Al.

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Pathogenic variants in the valosin-containing protein (

METHODS: A 6-item clinical score was developed to evaluate the phenotypic level of evidence to support the pathogenicity of the novel variants. Each item is allocated a value, a score ranging from 0.5 to 5.5 points. A receiver-operating characteristic curve was used to identify a cutoff value of 3 to consider a variant as high likelihood disease associated. The scoring system results were confronted with results of in vitro ATPase activity assays and with in silico analysis.

RESULTS: All variants were missense, except for one small deletion-insertion, 18 led to …

Modeling X-Chromosome Inactivation And Reactivation During Human Development, Shafqat A Khan, Thorold W Theunissen

2020-Current year OA Pubs

Stem-cell-based embryo models generate much excitement as they offer a window into an early phase of human development that has remained largely inaccessible to scientific investigation. An important epigenetic phenomenon during early embryogenesis is the epigenetic silencing of one of the two X chromosomes in female embryos, which ensures an equal output of X-linked gene expression between the sexes. X-chromosome inactivation (XCI) is thought to be established within the first three weeks of human development, although the inactive X-chromosome is reactivated in primordial germ cells (PGCs) that migrate to the embryonic gonads. Here, we summarize our current understanding of X-chromosome …

The Association Of Long-Term Exposure To Criteria Air Pollutants, Fine Particulate Matter Components, And Airborne Trace Metals With Late-Life Brain Amyloid Burden In The Atherosclerosis Risk In Communities (Aric) Study, Erin E Bennett, Dean F Wong, Et Al.

2020-Current year OA Pubs

BACKGROUND: Studies suggest associations between long-term ambient air pollution exposure and outcomes related to Alzheimer's disease (AD). Whether a link exists between pollutants and brain amyloid accumulation, a biomarker of AD, is unclear. We assessed whether long-term air pollutant exposures are associated with late-life brain amyloid deposition in Atherosclerosis Risk in Communities (ARIC) study participants.

METHODS: We used a chemical transport model with data fusion to estimate ambient concentrations of PM

RESULTS: At PET imaging, eligible participants (N = 318) had a mean age of 78 years, 56% were female, 43% were Black, and 27% had mild cognitive impairment. We …

Comprehensive Mr Imaging Qa Of 0.35 T Mr-Linac Using A Multi-Purpose Large Fov Phantom: A Single-Institution Experience, Shanti Marasini, Hailei Zhang, Lara Dyke, Mike Cole, Benjamin Quinn, Austen Curcuru, Bruce Gu, Rocco Flores, Taeho Kim

2020-Current year OA Pubs

PURPOSE: Magnetic resonance-guided radiotherapy (MRgRT) is desired for the treatment of diseases in the abdominothoracic region, which has a broad imaging area and continuous motion. To ensure accurate treatment delivery, an effective image quality assurance (QA) program, with a phantom that covers the field of view (FOV) similar to a human torso, is required. However, routine image QA for a large FOV is not readily available at many MRgRT centers. In this work, we present the clinical experience of the large FOV MRgRT Insight phantom for periodic daily and monthly comprehensive magnetic resonance imaging (MRI)-QA and its feasibility compared to …

Non-Small Cell Lung Cancer Epigenomes Exhibit Altered Dna Methylation In Smokers And Never-Smokers, Jennifer A Karlow, Erica C Pehrsson, Xiaoyun Xing, Mark Watson, Siddhartha Devarakonda, Ramaswamy Govindan, Ting Wang

2020-Current year OA Pubs

Epigenetic alterations are widespread in cancer and can complement genetic alterations to influence cancer progression and treatment outcome. To determine the potential contribution of DNAmethylation alterations to tumor phenotype in non-small cell lung cancer (NSCLC) in both smoker and never-smoker patients, we performed genome-wide profiling of DNA methylation in 17 primary NSCLC tumors and 10 matched normal lung samples using the complementary assays, methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation sensitive restriction enzyme sequencing (MRE-seq). We reported recurrent methylation changes in the promoters of several genes, many previously implicated in cancer, including FAM83A and SEPT9 (hypomethylation), as well as PCDH7, …

Allogeneic Hematopoietic Cell Transplantation Improves Outcome In Myelodysplastic Syndrome Across High-Risk Genetic Subgroups: Genetic Analysis Of The Blood And Marrow Transplant Clinical Trials Network 1102 Study, Jurjen Versluis, Peter Westervelt, Et Al.

2020-Current year OA Pubs

PURPOSE: Allogeneic hematopoietic cell transplantation (HCT) in patients with myelodysplastic syndrome (MDS) improves overall survival (OS). We evaluated the impact of MDS genetics on the benefit of HCT in a biological assignment (donor

METHODS: We performed targeted sequencing in 309 patients age 50-75 years with International Prognostic Scoring System (IPSS) intermediate-2 or high-risk MDS, enrolled in the Blood and Marrow Transplant Clinical Trials Network 1102 study and assessed the association of gene mutations with OS. Patients with

RESULTS: The distribution of gene mutations was similar in the donor and no donor arms, with

CONCLUSION: HCT improved OS compared with non-HCT …

Dmrt1 Regulates Human Germline Commitment, Naoko Irie, Sun-Min Lee, Valentina Lorenzi, Haiqi Xu, Jinfeng Chen, Masato Inoue, Toshihiro Kobayashi, Carmen Sancho-Serra, Elena Drousioti, Sabine Dietmann, Roser Vento-Tormo, Chun-Xiao Song, M Azim Surani

2020-Current year OA Pubs

Germline commitment following primordial germ cell (PGC) specification during early human development establishes an epigenetic programme and competence for gametogenesis. Here we follow the progression of nascent PGC-like cells derived from human embryonic stem cells in vitro. We show that switching from BMP signalling for PGC specification to Activin A and retinoic acid resulted in DMRT1 and CDH5 expression, the indicators of migratory PGCs in vivo. Moreover, the induction of DMRT1 and SOX17 in PGC-like cells promoted epigenetic resetting with striking global enrichment of 5-hydroxymethylcytosine and locus-specific loss of 5-methylcytosine at DMRT1 binding sites and the expression of DAZL representing …

Interrater Reliability Of Motor Severity Scales For Hemifacial Spasm, Ha Yeon Lee, Ingyun Park, Minnie P Luu, Jerry Zhao, Jeanne P Vu, Elizabeth Cisneros, Brian D Berman, H A Jinnah, Han-Joon Kim, Catherine Y Liu, Joel S Perlmutter, Sarah Pirio Richardson, Anne Weissbach, Glenn T Stebbins, David A Peterson

2020-Current year OA Pubs

To compare the inter-rater reliability (IRR) of five clinical rating scales for video-based assessment of hemifacial spasm (HFS) motor severity. We evaluated the video recordings of 45 HFS participants recruited through the Dystonia Coalition. In Round 1, six clinicians with expertise in HFS assessed the participants' motor severity with five scales used to measure motor severity of HFS: the Jankovic rating scale (JRS), Hemifacial Spasm Grading Scale (HSGS), Samsung Medical Center (SMC) grading system for severity of HFS spasms (Lee's scale), clinical grading of spasm intensity (Chen's scale), and a modified version of the Abnormal Involuntary Movement Scale (Tunc's scale). …

Good Manufacturing Practice Production Of Cd34+ Progenitor-Derived Nk Cells For Adoptive Immunotherapy In Acute Myeloid Leukemia, P K J D De Jonge, P M M Van Hauten, L D Janssen, A L De Goede, M M Berrien-Elliott, J M R Van Der Meer, C M Mousset, M W H Roeven, M Foster, N Blijlevens, W Hobo, T A Fehniger, J H Jansen, N P M Schaap, H Dolstra

2020-Current year OA Pubs

Allogeneic natural killer (NK) cell-based immunotherapy is a promising, well-tolerated adjuvant therapeutic approach for acute myeloid leukemia (AML). For reproducible NK cell immunotherapy, a homogenous, pure and scalable NK cell product is preferred. Therefore, we developed a good manufacturing practice (GMP)-compliant, cytokine-based ex vivo manufacturing process for generating NK cells from CD34

Evaluating Adult Care In Dravet Syndrome Upon Transferring From Pediatrics In The U.S.: A Caregiver-Based Survey Study, Fábio A Nascimento, Veronica Hood, Samantha V Yap, Irfan S Sheikh, Mary Anne Meskis, Elizabeth A Thiele

2020-Current year OA Pubs

Patients with Dravet syndrome (DS) and their caregivers must navigate a complex process upon transitioning from pediatric to adult healthcare settings. Our study examines the state of care transfer of patients with DS in the U.S. A 34-question e-survey evaluating patient demographics, clinical features, and details of the transfer process was sent to caregivers of adults with DS (≥18 years old) residing in the U.S. through the Dravet Syndrome Foundation. Forty-six responses were included in the analysis. Twenty-nine patients (n = 29/46) did not undergo transfer of care - mostly because they were still followed by pediatric neurologists/epileptologists (71%), whereas …

Introduction To A Compendium Of Strategies To Prevent Healthcare-Associated Infections In Acute-Care Hospitals: 2022 Updates, Deborah S Yokoe, Hilary M Babcock, Erik R Dubberke, Jonas Marschall, Et Al.

2020-Current year OA Pubs

Since the initial publication of

Intra-Individual Variability Adaptively Increases Following Inhibition Training During Middle Childhood, Roser Cañigueral, Keertana Ganesan, Claire R Smid, Abigail Thompson, Nico U F Dosenbach, Nikolaus Steinbeis

2020-Current year OA Pubs

There is ongoing debate on the relationship between intra-individual variability (IIV) of cognitive processes and task performance. While psychological research has traditionally assumed that lower intra-individual variability (IIV) aids consistent task performance, some studies suggest that greater IIV can also be adaptive, especially when flexible responding is required. Here we selectively manipulate inhibitory control (Stopping) and response speed (Going) by means of a training paradigm to 1) assess how this manipulation impacts Stopping IIV and its relationship to task performance, and 2) replicate previous findings showing that reductions in Going IIV are adaptive. A group of 208 6-13-year-old children were …

Antibody Response To Sars-Cov-2 Vaccines In Patients With Relapsing Multiple Sclerosis Treated With Evobrutinib: A Bruton's Tyrosine Kinase Inhibitor, Amit Bar-Or, Anne H Cross, Anthony L Cunningham, Yann Hyvert, Andrea Seitzinger, Hans Gühring, Elise E Drouin, Nektaria Alexandri, Davorka Tomic, Xavier Montalban

2020-Current year OA Pubs

BACKGROUND: Evobrutinib is an oral, central nervous system (CNS)-penetrant and highly selective covalent Bruton's tyrosine kinase inhibitor under clinical development for patients with relapsing multiple sclerosis (RMS).

OBJECTIVE: To investigate the effect of evobrutinib on immune responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinated patients with RMS from a Phase II trial (NCT02975349).

METHODS: A

RESULTS: In the vaccinated subgroup, mean/minimum evobrutinib exposure pre-vaccination was 105.2/88.7 weeks. In total, 43 of 45 patients developed/increased S1/S2 IgG antibody levels post-vaccination; one patient's antibody response remained negative post-vaccination and the other had antibody levels above the upper limit of detection, …

N7-Methylguanosine Methylation Of Trnas Regulates Survival To Stress In Cancer, Raquel García-Vílchez, Ana M Añazco-Guenkova, Judith López, Sabine Dietmann, Mercedes Tomé, Sonia Jimeno, Mikel Azkargorta, Félix Elortza, Laura Bárcena, Monika Gonzalez-Lopez, Ana M Aransay, Manuel A Sánchez-Martín, Pablo Huertas, Raúl V Durán, Sandra Blanco

2020-Current year OA Pubs

Tumour progression and therapy tolerance are highly regulated and complex processes largely dependent on the plasticity of cancer cells and their capacity to respond to stress. The higher plasticity of cancer cells highlights the need for identifying targetable molecular pathways that challenge cancer cell survival. Here, we show that N

Development Of A Comprehensive Cardiac Atlas On A 1.5 Tesla Magnetic Resonance Linear Accelerator, Aronne M Schottstaedt, Eric S Paulson, Jason C Rubenstein, Xinfeng Chen, Eenas A Omari, X Allen Li, Chris J Schultz, Lindsay L Puckett, Clifford G Robinson, Filippo Alongi, Elizabeth M Gore, William A Hall

2020-Current year OA Pubs

BACKGROUND AND PURPOSE: The 1.5 Tesla (T) Magnetic Resonance Linear Accelerator (MRL) provides an innovative modality for improved cardiac imaging when planning radiation treatment. No MRL based cardiac atlases currently exist, thus, we sought to comprehensively characterize cardiac substructures, including the conduction system, from cardiac images acquired using a 1.5 T MRL and provide contouring guidelines.

MATERIALS AND METHODS: Five volunteers were enrolled in a prospective protocol (NCT03500081) and were imaged on the 1.5 T MRL with Half Fourier Single-Shot Turbo Spin-Echo (HASTE) and 3D Balanced Steady-State Free Precession (bSSFP) sequences in axial, short axis, and vertical long axis. Cardiac …

Immune Adjuvant Therapy With Interleukin-7 In A Lymphopenic Patient With Aplastic Anemia And Mucormycosis, Zachary D. Crees, Dilan A. Patel, Alexandra Dram, Miriam Kim, Michael D. Bern, Allison R. Eberly, Kristan Augustin, Richard S. Hotchkiss, John F. Dipersio

2020-Current year OA Pubs

BACKGROUND: We report the case of a patient with aplastic anemia and pancytopenia on immune-suppressive therapy who developed invasive pulmonary infection with mucormycosis and was treated with immune adjuvant therapy.

CASE SUMMARY: Given the patient's profound lymphopenia and progressive invasive mucor despite dual antifungal drug therapy, interleukin (IL)-7, a cytokine that induces lymphocyte activation and proliferation, was instituted and resulted in normalization of absolute lymphocyte counts and was temporally associated with clearance of fungal pathogens and resolution of clinical symptoms.

CONCLUSION: Patients with life-threatening fungal infections are frequently immune suppressed and immune adjuvant therapies should be considered in patients who …

Characterization Of Copy-Number Variants In A Large Cohort Of Patients With Von Willebrand Disease Reveals A Relationship Between Disrupted Regions And Disease Type, Brooke Sadler, Pamela A Christopherson, Crystal L Perry, Daniel B Bellissimo, Sandra L Haberichter, Gabe Haller, Lilian Antunes, Veronica H Flood, Jorge Di Paola, Robert R Montgomery, Zimmerman Program Investigators

2020-Current year OA Pubs

BACKGROUND: Genetic analysis for von Willebrand disease (VWD) commonly utilizes DNA sequencing to identify variants in the von Willebrand factor (

OBJECTIVES: This study aimed to characterize CNVs in a large sample of VWF mutation-negative VWD patients.

METHODS: To determine the role of CNVs in VWD, a VWF high-resolution comparative genomic hybridization array was custom-designed to avoid multiple sequence variations, repeated sequences, and the

RESULTS: Among the 204 patients, 7 unique CNVs were found, with a total of 24 CNVs (12%). Of the 7 unique CNVs, 1 was novel, 1 was found in a VWF database, and 5 were previously …

Knowledge, Beliefs, And Practices Related To Coronavirus Disease 2019 (Covid-19) Infection And Vaccination In Healthcare Personnel Working At Nonacute Care Facilities, Armaghan-E-Rehman Mansoor, Caroline A O'Neil, David Mcdonald, Victoria J Fraser, Hilary M Babcock, Jennie H Kwon, Cdc Prevention Epicenters Program

2020-Current year OA Pubs

OBJECTIVE: To characterize experiences, beliefs, and perceptions of risk related to coronavirus disease 2019 (COVID-19), infection prevention practices, and COVID-19 vaccination among healthcare personnel (HCP) at nonacute care facilities.

DESIGN: Anonymous survey.

SETTING: Three non-acute-care facilities in St. Louis, Missouri.

PARTICIPANTS: In total, 156 HCP responded to the survey, for a 25.6% participation rate). Among them, 32% had direct patient-care roles.

METHODS: Anonymous surveys were distributed between April-May 2021. Data were collected on demographics, work experience, COVID-19 exposure, knowledge, and beliefs about infection prevention, personal protective equipment (PPE) use, COVID-19 vaccination, and the impact of COVID-19.

RESULTS: Nearly all respondents …

Is Retention Of The Acetabular Component At Revision Surgery A Long-Term Solution?, Elizabeth Lieberman, Lee Sasala, Tanner Thornton, Robert Barrack, Ryan Nunley, Susan Thapa, John Clohisy

2020-Current year OA Pubs

BACKGROUND: Acetabular retention in revision total hip arthroplasty (THA) may be advantageous, yet long-term survival data is limited. Thus, we investigated long-term survivorship of retained acetabular components in revision THA with analysis of rerevision rate, instability risk, and clinical outcomes.

METHODS: We reviewed 98 hips with polyethylene wear and/or osteolysis that were revised with retained acetabular components. Acetabular inclination and anteversion were measured from prerevision radiographs. A retrospective chart review was performed, collecting outcomes of interest including Harris hip score, instability events, and rerevision surgery. Kaplan-Meier analysis was used to calculate the risk of revision over time. Predictors of survival …

Coverage For Continuous Glucose Monitoring For Individuals With Type 2 Diabetes Treated With Nonintensive Therapies: An Evidence-Based Approach To Policymaking, Grazia Aleppo, Irl B Hirsch, Christopher G Parkin, Janet Mcgill, Rodolfo Galindo, Davida F Kruger, Carol J Levy, Gregory P Forlenza, Guillermo E Umpierrez, George Grunberger, Richard M Bergenstal

2020-Current year OA Pubs

Numerous studies have demonstrated the clinical benefits of continuous glucose monitoring (CGM) in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) who are treated with intensive insulin regimens. Based on this evidence, CGM is now a standard of care for individuals within these diabetes populations and widely covered by commercial and public insurers. Moreover, recent clinical guidelines from the American Diabetes Association and American Association of Clinical Endocrinology now endorse CGM use in individuals treated with nonintensive insulin regimens. However, despite increasing evidence supporting CGM use for individuals treated with less-intensive insulin therapy or noninsulin medications, insurance …

Short Tandem Repeat Profiling Via Next-Generation Sequencing For Cell Line Authentication, Yi-Hsien Chen, Jon P Connelly, Colin Florian, Xiaoxia Cui, Shondra M Pruett-Miller

2020-Current year OA Pubs

Cell lines are indispensable models for modern biomedical research. A large part of their usefulness derives from the ability of a cell line to proliferate over multiple passages (often indefinitely), allowing multiple experiments to be performed. However, over time, cell line identity and purity can be compromised by human errors. Cross-contamination from other cell lines and complete misidentification are both possible. Routine cell line authentication is a necessary preventive measure and has become a requirement for many funding applications and publications. Short tandem repeat (STR) profiling is the most common method for cell line authentication and is usually carried out …

Predicting Severe Disease In Patients Diagnosed With Seasonal Influenza In The Emergency Department, Michael J Pajor, Satish Munigala, Dan Reynolds, Julie Zeigler, Danaye Gebru, Phillip V Asaro, Steven J Lawrence, Stephen Y Liang, Philip A Mudd

2020-Current year OA Pubs

OBJECTIVES: We sought to develop an evidence-based tool to risk stratify patients diagnosed with seasonal influenza in the emergency department (ED).

METHODS: We performed a single-center retrospective cohort study of all adult patients diagnosed with influenza in a large tertiary care ED between 2008 and 2018. We evaluated demographics, triage vital signs, chest x-ray and laboratory results obtained in the ED. We used univariate and multivariate statistics to examine the composite primary outcome of death or need for intubation. We validated our findings in patients diagnosed between 2018 and 2020.

RESULTS: We collected data from 3128 subjects; 2196 in the …

Derivation, Validation, And Clinical Relevance Of A Pediatric Sepsis Phenotype With Persistent Hypoxemia, Encephalopathy, And Shock, L. Nelson Sanchez-Pinto, Tellen D. Bennett, Emily K. Stroup, Yuan Luo, Mihir Atreya, Juliane Bubeck-Wardenburg, Grace Chong, Alon Geva, E. Vincent S. Faustino, Reid W. Farris, Mark W. Hall, Colin Rogerson, Sareen S. Shah, Scott L. Weiss, Robinder G. Khemani

2020-Current year OA Pubs

OBJECTIVES: Untangling the heterogeneity of sepsis in children and identifying clinically relevant phenotypes could lead to the development of targeted therapies. Our aim was to analyze the organ dysfunction trajectories of children with sepsis-associated multiple organ dysfunction syndrome (MODS) to identify reproducible and clinically relevant sepsis phenotypes and determine if they are associated with heterogeneity of treatment effect (HTE) to common therapies.

DESIGN: Multicenter observational cohort study.

SETTING: Thirteen PICUs in the United States.

PATIENTS: Patients admitted with suspected infections to the PICU between 2012 and 2018.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We used subgraph-augmented nonnegative matrix factorization to …

New Devices In Glaucoma, Lilian Chan, Marlene R Moster, Amanda K Bicket, Arsham Sheybani, Steven R Sarkisian, Thomas W Samuelson, Iqbal Ike K Ahmed, Eydie Miller-Ellis, Oluwatosin U Smith, Qi N Cui

2020-Current year OA Pubs

Glaucoma remains a leading cause of blindness globally. Minimally invasive treatment techniques are rapidly expanding the availability of therapeutic options for glaucoma. These include devices aimed at enhancing outflow through the subconjunctival space, Schlemm's canal, and suprachoroidal space, sustained-release drug delivery devices, and extraocular devices aiming to reduce glaucomatous progression through other novel means. In this review, we provide an overview of several novel devices either newly available or in development for the medical and surgical management of glaucoma. Further studies are required to determine the long-term efficacy of these devices and how they will integrate into the current landscape …

Pancreatic Tail Cancer In The Setting Of Pancreatitis With A Review Of The Literature: A Case Report, Shinji Rho, Sooyoung Martin, Zack Nigogosyan, Vladimir Kushnir, Aaron J Mintz, Zishuo Ian Hu

2020-Current year OA Pubs

Environmental risk factors for pancreatic cancer include acute and chronic pancreatitis, obesity, and tobacco use. Differentiating a pancreatic neoplasm in a patient with pancreatitis can be challenging due to their similar presentations. A 57-year-old African American man with a history of congestive heart failure, pancreatitis, and incomplete pancreas divisum presented with an epigastric abdominal pain that radiated to his back. Imaging showed necrotizing pancreatitis, a developing splenic infarct, and a mass at the pancreas tail. The patient was discharged with pain medications and was recommended follow-up imaging after resolution of his pancreatitis. He was readmitted to the emergency department 2 …

The Effect Of Glycemic Control On Left Ventricular Function In Clinical And Experimental Diabetes, Steven J Lavine, Petar Prcevski

2020-Current year OA Pubs

BACKGROUND: Glycemic control in diabetes mellitus (DM) has not improved cardiovascular outcomes with normal left ventricular (LV) function. We assessed the effect on LV dysfunction using a canine model of LV dysfunction and DM, and in patients with DM and LV dysfunction.

METHODS: Chronic LV dysfunction was produced by coronary microsphere embolization in 34 canines (15-25 kg). Following 8 weeks of stabilization, DM was induced in 24 canines and randomized to good or poor glycemic control for 3 months. Ten canines without DM were controls. Hemodynamic and Doppler echocardiographic data were obtained prior to and following pressure loading. We reviewed …

Polygenic Risk Score Predicts Risk Of Primary Sclerosing Cholangitis In Inflammatory Bowel Disease, Ming-Hsi Wang, Jessica J Friton, Laura E Raffals, Jonathan A Leighton, Shabana F Pasha, Michael F Picco, Kelly Monroe, Billy D Nix, Rodney D Newberry, William A Faubion

2020-Current year OA Pubs

BACKGROUND: Forty distinct primary sclerosing cholangitis (PSC) genomic loci have been identified through multiancestry meta-analyses. The polygenic risk score (PRS) could serve as a promising tool to discover unique disease behaviour, like PSC, underlying inflammatory bowel disease (IBD).

AIM: To test whether PRS indicates PSC risk in patients with IBD.

MATERIALS AND METHODS: Mayo Clinic and Washington University at St Louis IBD cohorts were used to test our hypothesis. PRS was modelled through the published PSC loci and weighted with their corresponding effect size. Logistic regression was applied to predict the PSC risk.

RESULTS: In total, 63 (5.6%) among 1130 …