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A Phase 1/2 Open Label Nonrandomized Clinical Trial Of Intravenous 2-Hydroxypropyl-Β-Cyclodextrin For Acute Liver Disease In Infants With Niemann-Pick C1, Margaret Reynolds, Laura A Linneman, Sofia Luna, Barbara B Warner, Yumirle P Turmelle, Sakil S Kulkarni, Xuntian Jiang, Geetika Khanna, Marwan Shinawi, Forbes D Porter, Daniel S Ory, F. Sessions Cole, Patricia I Dickson Sep 2021

A Phase 1/2 Open Label Nonrandomized Clinical Trial Of Intravenous 2-Hydroxypropyl-Β-Cyclodextrin For Acute Liver Disease In Infants With Niemann-Pick C1, Margaret Reynolds, Laura A Linneman, Sofia Luna, Barbara B Warner, Yumirle P Turmelle, Sakil S Kulkarni, Xuntian Jiang, Geetika Khanna, Marwan Shinawi, Forbes D Porter, Daniel S Ory, F. Sessions Cole, Patricia I Dickson

Open Access Publications

Introduction: Niemann-Pick C (NPC) is an autosomal recessive disease due to defective NPC1 or NPC2 proteins resulting in

Methods: Infants received intravenous 2HPBCD twice a week for 6 weeks, followed by monthly infusion for 6-months. Primary outcome measure was reduction of plasma (3β,5α,6β-trihydroxy-cholan-24-oyl) glycine (TCG), a bile acid generated from cholesterol sequestered in lysosome.

Results: Three participants completed this protocol. A fourth patient received intravenous 2HPBCD under an emergency investigational new drug study but later expired from her underlying condition. The three protocol patients are living and have improved liver enzymes and TCG. No patient has experienced a drug-related adverse …


Mapt R406w Increases Tau T217 Phosphorylation In Absence Of Amyloid Pathology, Chihiro Sato, Nipun Mallipeddi, Nupur Ghoshal, Brenton A Wright, Gregory S Day, Albert A Davis, Albert H Kim, Gregory J Zipfel, Randall J Bateman, Audrey Gabelle, Nicolas R Barthélemy Sep 2021

Mapt R406w Increases Tau T217 Phosphorylation In Absence Of Amyloid Pathology, Chihiro Sato, Nipun Mallipeddi, Nupur Ghoshal, Brenton A Wright, Gregory S Day, Albert A Davis, Albert H Kim, Gregory J Zipfel, Randall J Bateman, Audrey Gabelle, Nicolas R Barthélemy

Open Access Publications

OBJECTIVE: Tau hyperphosphorylation at threonine 217 (pT217) in cerebrospinal fluid (CSF) has recently been linked to early amyloidosis and could serve as a highly sensitive biomarker for Alzheimer's disease (AD). However, it remains unclear whether other tauopathies induce pT217 modifications. To determine if pT217 modification is specific to AD, CSF pT217 was measured in AD and other tauopathies.

METHODS: Using immunoprecipitation and mass spectrometry methods, we compared CSF T217 phosphorylation occupancy (pT217/T217) and amyloid-beta (Aβ) 42/40 ratio in cognitively normal individuals and those with symptomatic AD, progressive supranuclear palsy, corticobasal syndrome, and sporadic and familial frontotemporal dementia.

RESULTS: Individuals with …


Interplay Of Trypanosome Lytic Factor And Innate Immune Cells In The Resolution Of Cutaneous Leishmania Infection, Jyoti Pant, Marie Samanovic, Maria T. Nelson, Mert K. Keceli, Joseph Verdi, Stephen M. Beverley, Jayne Raper Sep 2021

Interplay Of Trypanosome Lytic Factor And Innate Immune Cells In The Resolution Of Cutaneous Leishmania Infection, Jyoti Pant, Marie Samanovic, Maria T. Nelson, Mert K. Keceli, Joseph Verdi, Stephen M. Beverley, Jayne Raper

Open Access Publications

Trypanosome Lytic Factor (TLF) is a primate-specific high-density lipoprotein (HDL) complex that, through the cation channel-forming protein apolipoprotein L-1 (APOL1), provides innate immunity to select kinetoplastid parasites. The immunoprotective effects of TLF have been extensively investigated in the context of its interaction with the extracellular protozoan Trypanosoma brucei brucei, to which it confers sterile immunity. We previously showed that TLF could act against an intracellular pathogen Leishmania, and here we dissected the role of TLF and its synergy with host-immune cells. Leishmania major is transmitted by Phlebotomine sand flies, which deposit the parasite intradermally into mammalian hosts, where neutrophils are …


A Novel Intervention Combining Supplementary Food And Infection Control Measures To Improve Birth Outcomes In Undernourished Pregnant Women In Sierra Leone: A Randomized, Controlled Clinical Effectiveness Trial, David Taylor Hendrixson, Kristie Smith, Patrick Lasowski, Meghan Callaghan-Gillespie, Jacklyn Weber, Peggy Papathakis, Per Ole Iversen, Aminata Shamit Koroma, Mark J. Manary Sep 2021

A Novel Intervention Combining Supplementary Food And Infection Control Measures To Improve Birth Outcomes In Undernourished Pregnant Women In Sierra Leone: A Randomized, Controlled Clinical Effectiveness Trial, David Taylor Hendrixson, Kristie Smith, Patrick Lasowski, Meghan Callaghan-Gillespie, Jacklyn Weber, Peggy Papathakis, Per Ole Iversen, Aminata Shamit Koroma, Mark J. Manary

Open Access Publications

BACKGROUND: Innovations for undernourished pregnant women that improve newborn survival and anthropometry are needed to achieve the Sustainable Development Goals 1 and 3. This study tested the hypothesis that a combination of a nutritious supplementary food and several proven chemotherapeutic interventions to control common infections would increase newborn weight and length in undernourished pregnant women.

METHODS AND FINDINGS: This was a prospective, randomized, controlled clinical effectiveness trial of a ready-to-use supplementary food (RUSF) plus anti-infective therapies compared to standard therapy in undernourished pregnant women in rural Sierra Leone. Women with a mid-upper arm circumference (MUAC) ≤23.0 cm presenting for antenatal …


Future Directions For Hiv Service Delivery Research: Research Gaps Identified Through Who Guideline Development, Nathan Ford, Ingrid Eshun-Wilson, Wole Ameyan, Morkor Newman, Lara Vojnov, Meg Doherty, Elvin Geng Sep 2021

Future Directions For Hiv Service Delivery Research: Research Gaps Identified Through Who Guideline Development, Nathan Ford, Ingrid Eshun-Wilson, Wole Ameyan, Morkor Newman, Lara Vojnov, Meg Doherty, Elvin Geng

Open Access Publications

Nathan Ford and co-authors discuss the systematic identification of research gaps in improving HIV service delivery.


Reactive Arthritis Post-Sars-Cov-2, Faizal Ouedraogo, Rachita Navara, Rusha Thapa, Kunj G. Patel Sep 2021

Reactive Arthritis Post-Sars-Cov-2, Faizal Ouedraogo, Rachita Navara, Rusha Thapa, Kunj G. Patel

Open Access Publications

Reactive arthritis (ReA) following bacterial infection from the urogenital and gastrointestinal tract is widely described but is not typical post-viral infections. This report presents the second case of ReA after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States. A 45-year-old black male with chronic low back pain was hospitalized for 45 days with coronavirus disease 2019 (COVID-19), complicated due to the development of multiorgan failure managed with intubation, extracorporeal membrane oxygenation, and hemodialysis. He was subsequently discharged to an acute rehabilitation facility where he complained of new-onset pain in his shoulders, left elbow, and left knee …


Evaluation Of Admission Chest X-Ray Findings In Patients With Respiratory Infection During The Covid-19 Pandemic, Dimitrios Velissaris, Maria Lagadinou, Themistoklis Paraskevas, Eleousa Oikonomou, Vasileios Karamouzos, Fotios Sampsonas, Markos Marangos, Menelaos Karanikolas Sep 2021

Evaluation Of Admission Chest X-Ray Findings In Patients With Respiratory Infection During The Covid-19 Pandemic, Dimitrios Velissaris, Maria Lagadinou, Themistoklis Paraskevas, Eleousa Oikonomou, Vasileios Karamouzos, Fotios Sampsonas, Markos Marangos, Menelaos Karanikolas

Open Access Publications

AIMS: To evaluate the prevalence of X-ray findings in hospitalized patients requiring hospitalization with suspected Coronavirus disease 2019 (COVID-19) infection and potential differences in the laboratory values and clinical outcomes related to the presence of abnormal chest X-ray (CXR) findings.

METHODS:

RESULTS:

CONCLUSION: CXR is a routine examination in all patients with symptoms of lower respiratory tract disease and its findings relate to in-hospital mortality and PaO


Covid-19 In Patients With Neuromyelitis Optica Spectrum Disorders And Myelin Oligodendrocyte Glycoprotein Antibody Disease In North America: From The Covims Registry, Scott D Newsome, Anne H Cross, Robert J Fox, June Halper, Pamela Kanellis, Bruce Bebo, David Li, Gary R Cutter, Kottil W Rammohan, Amber Salter Sep 2021

Covid-19 In Patients With Neuromyelitis Optica Spectrum Disorders And Myelin Oligodendrocyte Glycoprotein Antibody Disease In North America: From The Covims Registry, Scott D Newsome, Anne H Cross, Robert J Fox, June Halper, Pamela Kanellis, Bruce Bebo, David Li, Gary R Cutter, Kottil W Rammohan, Amber Salter

Open Access Publications

BACKGROUND AND OBJECTIVE: To describe the impact of coronavirus disease 2019 (COVID-19) on people with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD).

METHODS: The COVID-19 Infections in Multiple Sclerosis (MS) and Related Diseases (COViMS) Registry collected data on North American patients with MS and related diseases with laboratory-positive or highly suspected SARS-CoV-2 infection. Deidentified data were entered into a web-based registry by health care providers. Data were analyzed using

RESULTS: As of June 7, 2021, 77 patients with NMOSD and 20 patients with MOGAD were reported in the COViMS Registry. Most patients with NMOSD were …


Impact Of Nerve Surgery On Opioid And Medication Use In Patients With Chronic Nerve Injuries, John M Felder, Ivica Ducic Sep 2021

Impact Of Nerve Surgery On Opioid And Medication Use In Patients With Chronic Nerve Injuries, John M Felder, Ivica Ducic

Open Access Publications

Introduction: Limited information is available regarding the ability of nerve surgery to affect medication use patterns in patients with chronic pain or neuropathy due to nerve injury.

Methods: A retrospective survey was distributed to all operative patients (N = 767) from a single nerve surgeon's practice between 2014 and 2020. Data collected included demographics, specifics of the injury and symptoms, medication and opioid use before surgery, and medication/opioid use following surgery.

Results: Out of the 767 patients, 209 (27.2%) completed the survey. Average age was 48.8 (SD = 19.1) years; 68.9% female and 31.1% male. More than 50% of the …


Thrombolysis Improves Reperfusion And The Clinical Outcome In Tandem Occlusion Stroke Related To Cervical Dissection: Titan And Etis Pooled Analysis, Gaultier Marnat, Mohammad Anadani, Et Al Sep 2021

Thrombolysis Improves Reperfusion And The Clinical Outcome In Tandem Occlusion Stroke Related To Cervical Dissection: Titan And Etis Pooled Analysis, Gaultier Marnat, Mohammad Anadani, Et Al

Open Access Publications

BACKGROUND AND PURPOSE: Despite the widespread adoption of mechanical thrombectomy (MT) for the treatment of large vessel occlusion stroke (LVOS) in the anterior circulation, the optimal strategy for the treatment tandem occlusion related to cervical internal carotid artery (ICA) dissection is still debated. This individual patient pooled analysis investigated the safety and efficacy of prior intravenous thrombolysis (IVT) in anterior circulation tandem occlusion related to cervical ICA dissection treated with MT.

METHODS: We performed a retrospective analysis of two merged prospective multicenter international real-world observational registries: Endovascular Treatment in Ischemic Stroke (ETIS) and Thrombectomy In TANdem occlusions (TITAN) registries. Data …


Anterior Cruciate Ligament Reconstruction With Concomitant Meniscal Repair: Is Graft Choice Predictive Of Meniscal Repair Success?, Hytham Salem, Laura Huston, Alexander Zajichek, Eric Mccarty, Armando Vidal, Jonathan Bravman, Kurt Spindler, Rachel Frank, Annunziato Amendola, Jack Andrish, Robert Brophy, Morgan Jones, Christopher Kaeding, Robert Marx, Matthew Matava, Richard Parker, Michelle Wolcott, Brian Wolf, Rick Wright Sep 2021

Anterior Cruciate Ligament Reconstruction With Concomitant Meniscal Repair: Is Graft Choice Predictive Of Meniscal Repair Success?, Hytham Salem, Laura Huston, Alexander Zajichek, Eric Mccarty, Armando Vidal, Jonathan Bravman, Kurt Spindler, Rachel Frank, Annunziato Amendola, Jack Andrish, Robert Brophy, Morgan Jones, Christopher Kaeding, Robert Marx, Matthew Matava, Richard Parker, Michelle Wolcott, Brian Wolf, Rick Wright

Open Access Publications

Background: When meniscal repair is performed during anterior cruciate ligament (ACL) reconstruction (ACLR), the effect of ACL graft type on meniscal repair outcomes is unclear.

Hypothesis: The authors hypothesized that meniscal repairs would fail at the lowest rate when concomitant ACLR was performed with bone--patellar tendon--bone (BTB) autograft.

Study Design: Cohort study; Level of evidence, 3.

Methods: Patients who underwent meniscal repair at primary ACLR were identified from a longitudinal, prospective cohort. Meniscal repair failures, defined as any subsequent surgical procedure addressing the meniscus, were identified. A logistic regression model was built to assess the association of graft type, patient-specific …


Efficacy And Safety Of Belimumab In Paediatric And Adult Patients With Systemic Lupus Erythematosus: An Across-Study Comparison, Hermine Brunner, Carlos Abud-Mendoza, Masaaki Mori, Clarissa Pilkington, Reema Syed, Syuji Takei, Diego Viola, Richard Furie, Sandra Navarra, Fengchun Zhang, Damon Bass, Gina Eriksson, Anne Hammer, Beulah Ji, Mohamed Okily, David Roth, Holly Quasny, Nicolino Ruperto Sep 2021

Efficacy And Safety Of Belimumab In Paediatric And Adult Patients With Systemic Lupus Erythematosus: An Across-Study Comparison, Hermine Brunner, Carlos Abud-Mendoza, Masaaki Mori, Clarissa Pilkington, Reema Syed, Syuji Takei, Diego Viola, Richard Furie, Sandra Navarra, Fengchun Zhang, Damon Bass, Gina Eriksson, Anne Hammer, Beulah Ji, Mohamed Okily, David Roth, Holly Quasny, Nicolino Ruperto

Open Access Publications

OBJECTIVE: To assess the efficacy and safety of belimumab in paediatric versus adult patients with systemic lupus erythematosus (SLE).

METHODS: We performed across-study comparisons of patients with active SLE who received belimumab or placebo, plus standard therapy, in PLUTO (paediatric phase II) and BLISS-52, BLISS-76, BLISS-NEA and EMBRACE (adult phase III). Analysed efficacy data included Week 52 SLE Responder Index (SRI)-4 response rate (EMBRACE: SRI with modified Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) proteinuria scoring (SRI-S2K)); SRI-4 response rate (EMBRACE: SRI-S2K) according to baseline disease activity indicators (Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity …


Early Experience Of Covid-19 Vaccination In Adults With Systemic Rheumatic Diseases: Results From The Covid-19 Global Rheumatology Alliance Vaccine Survey, Sebastian Eduardo Sattui, Jean Liew, Alfred Hyoungju Kim, Et Al Sep 2021

Early Experience Of Covid-19 Vaccination In Adults With Systemic Rheumatic Diseases: Results From The Covid-19 Global Rheumatology Alliance Vaccine Survey, Sebastian Eduardo Sattui, Jean Liew, Alfred Hyoungju Kim, Et Al

Open Access Publications

BACKGROUND: We describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine.

METHODS: From 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination.

RESULTS: We analysed 2860 adults with systemic rheumatic diseases who received COVID-19 vaccination (mean age 55.3 years, 86.7% female, 86.3% white). Types of COVID-19 vaccines were Pfizer-BioNTech (53.2%), Oxford/AstraZeneca (22.6%), Moderna (21.3%), …


A Study Of Elective Genome Sequencing And Pharmacogenetic Testing In An Unselected Population, Meagan Cochran, Kelly East, Veronica Greve, Melissa Kelly, Whitley Kelley, Troy Moore, Richard M Myers, Katherine Odom, Molly C Schroeder, David Bick Sep 2021

A Study Of Elective Genome Sequencing And Pharmacogenetic Testing In An Unselected Population, Meagan Cochran, Kelly East, Veronica Greve, Melissa Kelly, Whitley Kelley, Troy Moore, Richard M Myers, Katherine Odom, Molly C Schroeder, David Bick

Open Access Publications

BACKGROUND: Genome sequencing (GS) of individuals without a medical indication, known as elective GS, is now available at a number of centers around the United States. Here we report the results of elective GS and pharmacogenetic panel testing in 52 individuals at a private genomics clinic in Alabama.

METHODS: Individuals seeking elective genomic testing and pharmacogenetic testing were recruited through a private genomics clinic in Huntsville, AL. Individuals underwent clinical genome sequencing with a separate pharmacogenetic testing panel.

RESULTS: Six participants (11.5%) had pathogenic or likely pathogenic variants that may explain one or more aspects of their medical history. Ten …


Lung Epithelial Signaling Mediates Early Vaccine-Induced Cd4 + T Cell Activation And Mycobacterium Tuberculosis Control, Shibali Das, Nancy D Marin, Ekaterina Esaulova, Mushtaq Ahmed, Amanda Swain, Bruce A Rosa, Makedonka Mitreva, Javier Rangel-Moreno, Mihai G Netea, Luis B Barreiro, Maziar Divangahi, Maxim N Artyomov, Deepak Kaushal, Shabaana A Khader Aug 2021

Lung Epithelial Signaling Mediates Early Vaccine-Induced Cd4 + T Cell Activation And Mycobacterium Tuberculosis Control, Shibali Das, Nancy D Marin, Ekaterina Esaulova, Mushtaq Ahmed, Amanda Swain, Bruce A Rosa, Makedonka Mitreva, Javier Rangel-Moreno, Mihai G Netea, Luis B Barreiro, Maziar Divangahi, Maxim N Artyomov, Deepak Kaushal, Shabaana A Khader

Open Access Publications

Tuberculosis (TB) is one of the leading causes of death due to a single infectious agent. The development of a TB vaccine that induces durable and effective immunity to Mycobacterium tuberculosis (


Vesicular Stomatitis Virus Chimeras Expressing The Oropouche Virus Glycoproteins Elicit Protective Immune Responses In Mice, Sarah Hulsey Stubbs, Marjorie Cornejo Pontelli, Nischay Mishra, Changhong Zhou, Juliano De Paula Souza, Rosa Maria Mendes Viana, W Ian Lipkin, David M Knipe, Eurico Arruda, Sean P J Whelan Aug 2021

Vesicular Stomatitis Virus Chimeras Expressing The Oropouche Virus Glycoproteins Elicit Protective Immune Responses In Mice, Sarah Hulsey Stubbs, Marjorie Cornejo Pontelli, Nischay Mishra, Changhong Zhou, Juliano De Paula Souza, Rosa Maria Mendes Viana, W Ian Lipkin, David M Knipe, Eurico Arruda, Sean P J Whelan

Open Access Publications

Oropouche virus (OROV) infection of humans is associated with a debilitating febrile illness that can progress to meningitis or encephalitis. First isolated from a forest worker in Trinidad and Tobago in 1955, the arbovirus OROV has since been detected throughout the Amazon basin with an estimated 500,000 human infections over 60 years. Like other members of the family


Critical Care Service Delivery Across Healthcare Systems In Low-Income And Low-Middle-Income Countries: Protocol For A Systematic Review, Andrew George Lim, Nicole Benzoni, Et Al Aug 2021

Critical Care Service Delivery Across Healthcare Systems In Low-Income And Low-Middle-Income Countries: Protocol For A Systematic Review, Andrew George Lim, Nicole Benzoni, Et Al

Open Access Publications

INTRODUCTION: Critical care in low-income and low-middle income countries (LLMICs) is an underdeveloped component of the healthcare system. Given the increasing growth in demand for critical care services in LLMICs, understanding the current capacity to provide critical care is imperative to inform policy on service expansion. Thus, our aim is to describe the provision of critical care in LLMICs with respect to patients, providers, location of care and services and interventions delivered.

METHODS AND ANALYSIS: We will search PubMed/MEDLINE, Web of Science and EMBASE for full-text original research articles available in English describing critical care services that specify the location …


Host Fecal Mrnas Predicted Environmental Enteric Dysfunction Among Children With Moderate Acute Malnutrition In Sierra Leone, Akriti Singh, Isabel Potani, Stacy P Griswold, Devika Suri, Breanne Langlois, Ye Shen, Shelley M Walton, Kenneth Kwan Ho Chui, Mark J Manary, Patrick Webb, Beatrice L Rogers, Irwin H Rosenberg Aug 2021

Host Fecal Mrnas Predicted Environmental Enteric Dysfunction Among Children With Moderate Acute Malnutrition In Sierra Leone, Akriti Singh, Isabel Potani, Stacy P Griswold, Devika Suri, Breanne Langlois, Ye Shen, Shelley M Walton, Kenneth Kwan Ho Chui, Mark J Manary, Patrick Webb, Beatrice L Rogers, Irwin H Rosenberg

Open Access Publications

Examining the role of environmental enteric dysfunction (EED) in child growth requires noninvasive, field-appropriate biomarkers. Alternatives to the traditionally used lactulose:mannitol (L:M) test have been explored, but few studies have compared the L:M test to host fecal mRNA transcripts. The objectives of this study were to examine whether 1) host fecal mRNA transcripts could predict presence and severity of EED, measured using the L:M test, and 2) EED modifies the effect of specialized nutritious foods (SNFs) on recovery from moderate acute malnutrition (MAM). This substudy was nested within a cluster randomized trial comparing four SNFs in the treatment of MAM …


Progression Of Sars-Cov-2 Seroprevalence In St. Louis, Missouri, Through January 2021, Brittany K Smith, Andrew B Janowski, Arim C Fremont, Lucas J Adams, Ya-Nan Dai, Christopher W Farnsworth, Ann M Gronowski, Stephen M Roper, David Wang, Daved H Fremont Aug 2021

Progression Of Sars-Cov-2 Seroprevalence In St. Louis, Missouri, Through January 2021, Brittany K Smith, Andrew B Janowski, Arim C Fremont, Lucas J Adams, Ya-Nan Dai, Christopher W Farnsworth, Ann M Gronowski, Stephen M Roper, David Wang, Daved H Fremont

Open Access Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity was assessed for 3,066 individuals visiting hospitals in St. Louis, Missouri, during July 2020, November 2020, or January 2021. Seropositivity in children increased from 5.22% in July to 21.16% in January. In the same time frame, seropositivity among adults increased from 4.52% to 19.03%, prior to initiation of mass vaccination.


Device Design Modifications Informed By In Vitro Testing Of Bacterial Attachment Reduce Infection Rates Of Cochlear Implants In Clinical Practice, Lynne Turnbull, Roger Leigh, Rosalia Cavaliere, Sarah R Osvath, Laura M Nolan, Daniel Smyth, Kristien Verhoeven, Richard A Chole, Cynthia B Whitchurch Aug 2021

Device Design Modifications Informed By In Vitro Testing Of Bacterial Attachment Reduce Infection Rates Of Cochlear Implants In Clinical Practice, Lynne Turnbull, Roger Leigh, Rosalia Cavaliere, Sarah R Osvath, Laura M Nolan, Daniel Smyth, Kristien Verhoeven, Richard A Chole, Cynthia B Whitchurch

Open Access Publications

Recalcitrant chronic infections of implanted medical devices are often linked to the presence of biofilms. The prevention and treatment of medical device-associated infections is a major source of antibiotic use and driver of antimicrobial resistance globally. Lowering the incidence of infection in patients that receive implanted medical devices could therefore significantly improve antibiotic stewardship and reduce patient morbidity. Here we determined if modifying the design of an implantable medical device to reduce bacterial attachment, impacted the incidence of device-associated infections in clinical practice. Since the 1980s cochlear implants have provided long-term treatment of sensorineural hearing deficiency in hundreds of thousands …


Predictive Accuracy And Densitometric Analysis Of Point-Of-Care Immunoassay For Adenoviral Conjunctivitis, Spencer D Johnson, Mary K Migneco, Mathew S Margolis, Leonard W Haertter, Julia B Huecker, Richard S Buller, Gregory A Storch, Mae O Gordon, Et Al Aug 2021

Predictive Accuracy And Densitometric Analysis Of Point-Of-Care Immunoassay For Adenoviral Conjunctivitis, Spencer D Johnson, Mary K Migneco, Mathew S Margolis, Leonard W Haertter, Julia B Huecker, Richard S Buller, Gregory A Storch, Mae O Gordon, Et Al

Open Access Publications

Purpose: Accurate diagnosis of adenoviral conjunctivitis (Ad-Cs) is important for timely and appropriate patient management to reduce disease transmission. This study assessed the diagnostic accuracy of a commercially available point-of-care adenovirus immunoassay and determined whether its predictive accuracy is influenced by signal intensities of test result bands.

Methods: Point-of-care immunoassay (AdenoPlus) testing and quantitative polymerase chain reaction (qPCR) testing was performed on conjunctival swab samples obtained from eyes of 186 eligible adult participants with presumed infectious conjunctivitis and symptoms of ≤4 days. Masked observers assessed signal intensities of the immunoassay test and control bands using densitometry.

Results: Ad-Cs was confirmed …


Cd7-Deleted Hematopoietic Stem Cells Can Restore Immunity After Car T Cell Therapy, Miriam Y. Kim, Matthew L. Cooper, Miriam T. Jacobs, Julie K. Ritchey, Julia Hollaway, Todd A. Fehniger, John F. Dipersio Aug 2021

Cd7-Deleted Hematopoietic Stem Cells Can Restore Immunity After Car T Cell Therapy, Miriam Y. Kim, Matthew L. Cooper, Miriam T. Jacobs, Julie K. Ritchey, Julia Hollaway, Todd A. Fehniger, John F. Dipersio

Open Access Publications

Targeting T cell malignancies with universal CD7-targeting chimeric antigen receptor T cells (UCART7) can lead to profound immune deficiency due to loss of normal T and NK cells. While a small population of endogenous CD7- T cells exists, these cells are unlikely to be able to repopulate the entire immune repertoire after UCART7 treatment, as they are limited in number and proliferative capacity. To rescue T and NK cells after UCART7, we created hematopoietic stem cells genetically deleted for CD7 (CD7-KO HSCs). CD7-KO HSCs were able to engraft immunodeficient mice and differentiate into T and NK cells lacking CD7 expression. …


Sars-Cov-2 Infection Of The Pancreas Promotes Thrombofibrosis And Is Associated With New-Onset Diabetes, Mirza Muhammad Fahd Qadir, Manika Bhondeley, Wandy Beatty, Dina D Gaupp, Lara A Doyle-Meyers, Tracy Fischer, Ishitri Bandyopadhyay, Robert V Blair, Rudolf Bohm, Jay Rappaport, Eric Lazartigues, Richard S Vander Heide, Jay K Kolls, Xuebin Qin, Franck Mauvais-Jarvis Aug 2021

Sars-Cov-2 Infection Of The Pancreas Promotes Thrombofibrosis And Is Associated With New-Onset Diabetes, Mirza Muhammad Fahd Qadir, Manika Bhondeley, Wandy Beatty, Dina D Gaupp, Lara A Doyle-Meyers, Tracy Fischer, Ishitri Bandyopadhyay, Robert V Blair, Rudolf Bohm, Jay Rappaport, Eric Lazartigues, Richard S Vander Heide, Jay K Kolls, Xuebin Qin, Franck Mauvais-Jarvis

Open Access Publications

Evidence suggests an association between severe acute respiratory syndrome-cornavirus-2 (SARS-CoV-2) infection and the occurrence of new-onset diabetes. We examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), the cell entry factors for SARS-CoV-2, using publicly available single-cell RNA sequencing data sets, and pancreatic tissue from control male and female nonhuman primates (NHPs) and humans. We also examined SARS-CoV-2 immunolocalization in pancreatic cells of SARS-CoV-2-infected NHPs and patients who had died from coronavirus disease 2019 (COVID-19). We report expression of ACE2 in pancreatic islet, ductal, and endothelial cells in NHPs and humans. In pancreata from SARS-CoV-2-infected …


The Use Of Dexmedetomidine In The Emergency Department: A Cohort Study, Joseph Sinnott, Christopher V Holthaus, Enyo Ablordeppey, Brian T Wessman, Brian W Roberts, Brian M Fuller Aug 2021

The Use Of Dexmedetomidine In The Emergency Department: A Cohort Study, Joseph Sinnott, Christopher V Holthaus, Enyo Ablordeppey, Brian T Wessman, Brian W Roberts, Brian M Fuller

Open Access Publications

INTRODUCTION: Management of sedation, analgesia, and anxiolysis are cornerstone therapies in the emergency department (ED). Dexmedetomidine (DEX), a central alpha-2 agonist, is increasingly being used, and intensive care unit (ICU) data demonstrate improved outcomes in patients with respiratory failure. However, there is a lack of ED-based data. We therefore sought to: 1) characterize ED DEX use; 2) describe the incidence of adverse events; and 3) explore factors associated with adverse events among patients receiving DEX in the ED.

METHODS: This was a single-center, retrospective, cohort study of consecutive ED patients administered DEX (January 1, 2017-July 1, 2019) at an academic, …


Evaluation Of Total Body Weight Versus Adjusted Body Weight Liposomal Amphotericin B Dosing In Obese Patients, Michelle H Ting, Andrej Spec, Scott T Micek, David J Ritchie, Tamara Krekel Aug 2021

Evaluation Of Total Body Weight Versus Adjusted Body Weight Liposomal Amphotericin B Dosing In Obese Patients, Michelle H Ting, Andrej Spec, Scott T Micek, David J Ritchie, Tamara Krekel

Open Access Publications

Liposomal amphotericin B (LAmB) is used for various fungal infections, but it is unclear which dosing weight to use in obese patients. The purpose of this study was to compare clinical outcomes of adjusted body weight (adjBW) versus total body weight (TBW) dosing of LAmB. This single-center, retrospective cohort study included patients who received LAmB for definitive therapy and whose TBW exceeded 120% of their ideal body weight (IBW). Analyses were conducted for 3 mg/kg for adjBW versus TBW and 5 mg/kg for adjBW versus TBW. A total of 238 patients were included. For the 68 patients who received LAmB …


Rheumatic Heart Disease In The United States: Forgotten But Not Gone: Results Of A 10 Year Multicenter Review, Sarah R De Loizaga, Lakshmi R Gokanapudy Hahn, Et Al Aug 2021

Rheumatic Heart Disease In The United States: Forgotten But Not Gone: Results Of A 10 Year Multicenter Review, Sarah R De Loizaga, Lakshmi R Gokanapudy Hahn, Et Al

Open Access Publications

Background Recent evaluation of rheumatic heart disease (RHD) mortality demonstrates disproportionate disease burden within the United States. However, there are few contemporary data on US children living with acute rheumatic fever (ARF) and RHD. Methods and Results Twenty-two US pediatric institutions participated in a 10-year review (2008-2018) of electronic medical records and echocardiographic databases of children 4 to 17 years diagnosed with ARF/RHD to determine demographics, diagnosis, and management. Geocoding was used to determine a census tract-based socioeconomic deprivation index. Descriptive statistics of patient characteristics and regression analysis of RHD classification, disease severity, and initial antibiotic prescription according to community …


Association Between Diagnosis Code Expansion And Changes In 30-Day Risk-Adjusted Outcomes For Cardiovascular Diseases, Lauren Gilstrap, Rishi K Wadhera, Andrea M Austin, Stephen Kearing, Karen E Joynt Maddox, Robert W Yeh Aug 2021

Association Between Diagnosis Code Expansion And Changes In 30-Day Risk-Adjusted Outcomes For Cardiovascular Diseases, Lauren Gilstrap, Rishi K Wadhera, Andrea M Austin, Stephen Kearing, Karen E Joynt Maddox, Robert W Yeh

Open Access Publications

BACKGROUND In January 2011, Centers for Medicare and Medicaid Services expanded the number of inpatient diagnosis codes from 9 to 25, which may influence comorbidity counts and risk-adjusted outcome rates for studies spanning January 2011. This study examines the association between (1) limiting versus not limiting diagnosis codes after 2011, (2) using inpatient-only versus inpatient and outpatient data, and (3) using logistic regression versus the Centers for Medicare and Medicaid Services risk-standardized methodology and changes in risk-adjusted outcomes. METHODS AND RESULTS Using 100% Medicare inpatient and outpatient files between January 2009 and December 2013, we created 2 cohorts of fee-for-service …


Temporal Trends Of Covid-19 Mortality And Hospitalisation Rates: An Observational Cohort Study From The Us Department Of Veterans Affairs, Miao Cai, Benjamin Bowe, Yan Xie, Ziyad Al-Aly Aug 2021

Temporal Trends Of Covid-19 Mortality And Hospitalisation Rates: An Observational Cohort Study From The Us Department Of Veterans Affairs, Miao Cai, Benjamin Bowe, Yan Xie, Ziyad Al-Aly

Open Access Publications

OBJECTIVES: To investigate the temporal trends of 30-day mortality and hospitalisation in US Veterans with COVID-19 and 30-day mortality in hospitalised veterans with COVID-19 and to decompose the contribution of changes in the underlying characteristics of affected populations to these temporal changes.

DESIGN: Observational cohort study.

SETTING: US Department of Veterans Affairs.

PARTICIPANTS: 49 238 US veterans with a positive COVID-19 test between 20 March 2020 and 19 September 2020; and 9428 US veterans hospitalised with a positive COVID-19 test during the same period.

OUTCOME MEASURES: 30-day mortality rate and hospitalisation rate.

RESULTS: Between 20 March 2020 and 19 September …


Variant Allele Fraction Of Genomic Alterations In Circulating Tumor Dna (%Ctdna) Correlates With Suv, Amin Haghighat Jahromi, Matthew Zabel, Ryosuke Okamura, Carl K Hoh, Razelle Kurzrock Aug 2021

Variant Allele Fraction Of Genomic Alterations In Circulating Tumor Dna (%Ctdna) Correlates With Suv, Amin Haghighat Jahromi, Matthew Zabel, Ryosuke Okamura, Carl K Hoh, Razelle Kurzrock

Open Access Publications

The relationship between higher variant allele fraction (VAF) of genomic alterations in circulating tumor DNA (%ctDNA), an indicator of poor outcome, and maximum standardized uptake value (SUV


Year 1 Of The Bundled Payments For Care Improvement-Advanced Model, Karen E Joynt Maddox, E John Orav, Jie Zheng, Arnold M Epstein Aug 2021

Year 1 Of The Bundled Payments For Care Improvement-Advanced Model, Karen E Joynt Maddox, E John Orav, Jie Zheng, Arnold M Epstein

Open Access Publications

BACKGROUND: The Center for Medicare and Medicaid Innovation launched the Medicare Bundled Payments for Care Improvement-Advanced (BPCI-A) program for hospitals in October 2018. Information is needed about the effects of the program on health care utilization and Medicare payments.

METHODS: We conducted a modified segmented regression analysis using Medicare claims and including patients with discharge dates from January 2017 through September 2019 to assess differences between BPCI-A participants and two control groups: hospitals that never joined the BPCI-A program (nonjoining hospitals) and hospitals that joined the BPCI-A program in January 2020, after the conclusion of the intervention period (late-joining hospitals). …