Digital Commons Network^™

Longitudinal Care Cascade Outcomes Among People Eligible For Antiretroviral Therapy Who Are Newly Linking To Care In Zambia: A Multistate Analysis, Aaloke Mody, David V Glidden, Ingrid Eshun-Wilson, Kombatende Sikombe, Sandra Simbeza, Njekwa Mukamba, Paul Somwe, Laura K Beres, Jake Pry, Carolyn Bolton-Moore, Nancy Padian, Charles B Holmes, Izukanji Sikazwe, Elvin H Geng

2020-Current year OA Pubs

BACKGROUND: Retention in human immunodeficiency virus (HIV) care is dynamic, with patients frequently transitioning in and out of care. Analytical approaches (eg, survival analyses) commonly used to assess HIV care cascade outcomes fail to capture such transitions and therefore incompletely represent care outcomes over time.

METHODS: We analyzed antiretroviral therapy (ART)-eligible adults newly linking to care at 64 clinics in Zambia between 1 April 2014 and 31 July 2015. We used electronic medical record data and supplemented these with updated care outcomes ascertained by tracing a multistage random sample of patients lost to follow-up (LTFU, >90 days late for last …

Coronary Computed Tomography Angiography Compared With Single Photon Emission Computed Tomography Myocardial Perfusion Imaging As A Guide To Optimal Medical Therapy In Patients Presenting With Stable Angina: The Rescue Trial, Arthur E Stillman, Constantine Gatsonis, Joao A C Lima, Tao Liu, Bradley S Snyder, Jean Cormack, Vinay Malholtra, Mitchell D Schnall, James E Udelson, Udo Hoffmann, Pamela K Woodard, Rescue Investigators

Open Access Publications

Background The RESCUE (Randomized Evaluation of Patients with Stable Angina Comparing Utilization of Noninvasive Examinations) trial was a randomized, controlled, multicenter, comparative efficacy outcomes trial designed to assess whether initial testing with coronary computed tomographic angiography (CCTA) is noninferior to single photon emission computed tomography (SPECT) myocardial perfusion imaging in directing patients with stable angina to optimal medical therapy alone or optimal medical therapy with revascularization. Methods and Results The end point was first major adverse cardiovascular event (MACE) (cardiac death or myocardial infarction), or revascularization. Noninferiority margin for CCTA was set a priori as a hazard ratio (HR) of …

Positive Information Facilitates Response Inhibition In Older Adults Only When Emotion Is Task-Relevant, Samantha E Williams, Eric J Lenze, Jill D Waring

Open Access Publications

Emotional information is integral to everyday life and impacts a variety of cognitive abilities including response inhibition, a critical skill for maintaining appropriate and flexible behaviour. However, reported effects of emotion on response inhibition are inconsistent in younger adults, and very limited in older adults. Effects of aging are especially relevant because emotion regulation improves with aging despite declining inhibitory control over neutral information. Across three studies, we assessed the impact of emotional facial expressions on response inhibition in younger and older adults while manipulating attention to task stimuli. Emotional faces (versus neutral faces) altered response inhibition only when task …

A Randomized, Placebo-Controlled Trial Evaluating Effects Of Lebrikizumab On Airway Eosinophilic Inflammation And Remodelling In Uncontrolled Asthma (Clavier), Cary D Austin, Kaharu Sumino, Et Al.

2020-Current year OA Pubs

BACKGROUND: The anti-interleukin 13 (IL-13) monoclonal antibody lebrikizumab improves lung function in patients with moderate-to-severe uncontrolled asthma, but its effects on airway inflammation and remodelling are unknown. CLAVIER was designed to assess lebrikizumab's effect on eosinophilic inflammation and remodelling.

OBJECTIVE: To report safety and efficacy results from enrolled participants with available data from CLAVIER.

METHODS: We performed bronchoscopy on patients with uncontrolled asthma before and after 12 weeks of randomized double-blinded treatment with lebrikizumab (n = 31) or placebo (n = 33). The pre-specified primary end-point was relative change in airway subepithelial eosinophils per mm

RESULTS: There was a baseline …

Carfilzomib, Lenalidomide, And Dexamethasone Plus Transplant In Newly Diagnosed Multiple Myeloma, Jagoda K Jasielec, Ravi Vij, Et Al.

2020-Current year OA Pubs

In this phase 2 multicenter study, we evaluated the incorporation of autologous stem cell transplantation (ASCT) into a carfilzomib-lenalidomide-dexamethasone (KRd) regimen for patients with newly diagnosed multiple myeloma (NDMM). Transplant-eligible patients with NDMM received 4 cycles of KRd induction, ASCT, 4 cycles of KRd consolidation, and 10 cycles of KRd maintenance. The primary end point was rate of stringent complete response (sCR) after 8 cycles of KRd with a predefined threshold of ≥50% to support further study. Seventy-six patients were enrolled with a median age of 59 years (range, 40-76 years), and 35.5% had high-risk cytogenetics. The primary end point …

A Phase 1b Study Of Afm13 In Combination With Pembrolizumab In Patients With Relapsed Or Refractory Hodgkin Lymphoma, Nancy L Bartlett, Et Al.

2020-Current year OA Pubs

In relapsed/refractory Hodgkin lymphoma (R/R HL), immunotherapies such as the anti-programmed death-1 inhibitor pembrolizumab have demonstrated efficacy as monotherapy and are playing an increasingly prominent role in treatment. The CD30/CD16A-bispecific antibody AFM13 is an innate immune cell engager, a first-in-class, tetravalent antibody, designed to create a bridge between CD30 on HL cells and the CD16A receptor on natural killer cells and macrophages, to induce tumor cell killing. Early studies of AFM13 have demonstrated signs of efficacy as monotherapy for patients with R/R HL and the combination of AFM13 with pembrolizumab represents a rational new treatment modality. Here, we describe a …

Genetics And Geography Of Leukocyte Telomere Length In Sub-Saharan Africans, Steven C Hunt, Michael A Province, Et Al.

2020-Current year OA Pubs

Leukocyte telomere length (LTL) might be causal in cardiovascular disease and major cancers. To elucidate the roles of genetics and geography in LTL variability across humans, we compared LTL measured in 1295 sub-Saharan Africans (SSAs) with 559 African-Americans (AAms) and 2464 European-Americans (EAms). LTL differed significantly across SSAs (P = 0.003), with the San from Botswana (with the oldest genomic ancestry) having the longest LTL and populations from Ethiopia having the shortest LTL. SSAs had significantly longer LTL than AAms [P = 6.5(e-16)] whose LTL was significantly longer than EAms [P = 2.5(e-7)]. Genetic variation in SSAs explained 52% of …

Geff: Graph Embedding For Functional Fingerprinting, Kausar Abbas, Enrico Amico, Diana Otero Svaldi, Uttara Tipnis, Duy Anh Duong-Tran, Mintao Liu, Meenusree Rajapandian, Jaroslaw Harezlak, Beau M Ances, Joaquín Goñi

2020-Current year OA Pubs

It has been well established that Functional Connectomes (FCs), as estimated from functional MRI (fMRI) data, have an individual fingerprint that can be used to identify an individual from a population (subject-identification). Although identification rate is high when using resting-state FCs, other tasks show moderate to low values. Furthermore, identification rate is task-dependent, and is low when distinct cognitive states, as captured by different fMRI tasks, are compared. Here we propose an embedding framework, GEFF (Graph Embedding for Functional Fingerprinting), based on group-level decomposition of FCs into eigenvectors. GEFF creates an eigenspace representation of a group of subjects using one …

Prospective, Randomized, Double-Blind, Placebo-Controlled Evaluation Of The Pharmacokinetics, Safety And Efficacy Of Recombinant Antithrombin Versus Placebo In Preterm Preeclampsia, Michael J Paidas, George A Macones, Et Al

Open Access Publications

BACKGROUND: Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin, which displays antiinflammatory and anticoagulant properties, may have a therapeutic role in treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation, and activation of the coagulation system.

OBJECTIVE: This randomized, placebo-controlled clinical trial aimed to evaluate whether intravenous recombinant human antithrombin could prolong gestation and therefore improve maternal and fetal outcomes.

STUDY DESIGN: We performed a double-blind, placebo-controlled trial at 23 hospitals. Women were eligible if they had a singleton pregnancy, early-onset or superimposed preeclampsia at 23 0/7 to 30 0/7 weeks' gestation, and planned …

Brain Function Distinguishes Female Carriers And Non-Carriers Of Familial Risk For Autism, Adam T Eggebrecht, Ally Dworetsky, Zoë Hawks, Rebecca Coalson, Babatunde Adeyemo, Savannah Davis, Daniel Gray, Alana Mcmichael, Steven E Petersen, John N Constantino, John R Pruett

2020-Current year OA Pubs

BACKGROUND: Autism spectrum disorder (ASD) is characterized by high population-level heritability and a three-to-one male-to-female ratio that occurs independent of sex linkage. Prior research in a mixed-sex pediatric sample identified neural signatures of familial risk elicited by passive viewing of point light motion displays, suggesting the possibility that both resilience and risk of autism might be associated with brain responses to biological motion. To confirm a relationship between these signatures and inherited risk of autism, we tested them in families enriched for genetic loading through undiagnosed ("carrier") females.

METHODS: Using functional magnetic resonance imaging, we examined brain responses to passive …

Relationships Between Accelerometry And General Compensatory Movements Of The Upper Limb After Stroke, Jessica Barth, Joeseph W Klaesner, Catherine E Lang

2020-Current year OA Pubs

BACKGROUND: Standardized assessments are used in rehabilitation clinics after stroke to measure restoration versus compensatory movements of the upper limb. Accelerometry is an emerging tool that can bridge the gap between in- and out-of-clinic assessments of the upper limb, but is limited in that it currently does not capture the quality of a person's movement, an important concept to assess compensation versus restoration. The purpose of this analysis was to characterize how accelerometer variables may reflect upper limb compensatory movement patterns after stroke.

METHODS: This study was a secondary analysis of an existing data set from a Phase II, single-blind, …

Factor Structure Of The Opening Minds Stigma Scale For Health Care Providers And Psychometric Properties Of Its Hungarian Version, Dorottya Őri, Sándor Rózsa, Péter Szocsics, Lajos Simon, György Purebl, Zsuzsa Győrffy

2020-Current year OA Pubs

BACKGROUND: The Opening Minds Stigma Scale for Health Care Providers (OMS-HC) is a widely used questionnaire to measure the stigmatising attitudes of healthcare providers towards patients with mental health problems. The psychometric properties of the scale; however, have never been investigated in Hungary. We aimed to thoroughly explore the factor structure of the OMS-HC and examine the key psychometric properties of the Hungarian version.

METHODS: The OMS-HC is a self-report questionnaire that measures the overall stigmatising attitude by a total score, and three subscales can be calculated: Attitude, Disclosure and Help-seeking, and Social Distance. Our study population included specialists and …

Trem2 Activation On Microglia Promotes Myelin Debris Clearance And Remyelination In A Model Of Multiple Sclerosis, Francesca Cignarella, Fabia Filipello, Bryan Bollman, Claudia Cantoni, Alberto Locca, Robert Mikesell, Melissa Manis, Adiljan Ibrahim, Li Deng, Bruno A Benitez, Carlos Cruchaga, Danilo Licastro, Kathie Mihindukulasuriya, Oscar Harari, Michael Buckland, David M Holtzman, Arnon Rosenthal, Tina Schwabe, Ilaria Tassi, Laura Piccio

2020-Current year OA Pubs

Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) triggered by autoimmune mechanisms. Microglia are critical for the clearance of myelin debris in areas of demyelination, a key step to allow remyelination. TREM2 is expressed by microglia and promotes microglial survival, proliferation, and phagocytic activity. Herein we demonstrate that TREM2 was highly expressed on myelin-laden phagocytes in active demyelinating lesions in the CNS of subjects with MS. In gene expression studies, macrophages from subjects with TREM2 genetic deficiency displayed a defect in phagocytic pathways. Treatment with a new TREM2 agonistic antibody promoted the …

Comprehensive Pulmonary Safety Review Of Inhaled Technosphere® Insulin In Patients With Diabetes Mellitus, Janet B Mcgill, Anne Peters, John B Buse, Susanne Steiner, Tiffany Tran, Frank M Pompilio, David M Kendall

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVE: Technosphere

METHODS: Pooled data from 13 phase 2/3 clinical studies in 5505 patients with T1DM or T2DM treated with TI, Technosphere inhalation powder without insulin (TP; placebo), or active-comparator treatment were analyzed for incidences of respiratory treatment-emergent adverse events (TEAEs), changes in pulmonary function, and lung malignancies. Radiographic changes in the lungs were monitored in a subset of 229 patients.

RESULTS: Among 3017 patients receiving TI, the median duration of TI exposure was 168 days; median active-comparator and TP exposure durations were 363 and 149 days for 2198 and 290 patients, respectively. Respiratory TEAEs were comparable across …

Safety And Immunogenicity Of Fc-Eda, A Recombinant Ectodysplasin A1 Replacement Protein, In Human Subjects, Iris Körber, Ophir D Klein, Patrick Morhart, Florian Faschingbauer, Dorothy K Grange, Angus Clarke, Christine Bodemer, Silvia Maitz, Kenneth Huttner, Neil Kirby, Caroline Durand, Holm Schneider

2020-Current year OA Pubs

In X-linked hypohidrotic ectodermal dysplasia, the most frequent ectodermal dysplasia, an inherited deficiency of the signalling protein ectodysplasin A1 (EDA1) impairs the development of the skin and its appendages, various eccrine glands, and dentition. The severe hypohidrosis common to X-linked hypohidrotic ectodermal dysplasia patients may lead to life-threatening hyperthermia, especially during hot weather or febrile illness. Fc-EDA, an EDA1 replacement protein known to prevent the disease in newborn animals, was tested in 2 clinical trials (human adults and neonates) and additionally administered under compassionate use to 3 infants in utero. The data support the safety of Fc-EDA and efficacy if …

Phase 1 Study Of The Mdm2 Antagonist Ro6839921 In Patients With Acute Myeloid Leukemia, Geoffrey L Uy, Sarit Assouline, Anne-Marie Young, Steven Blotner, Brian Higgins, Lin-Chi Chen, Karen Yee

2020-Current year OA Pubs

In acute myeloid leukemia (AML), TP53 mutations and dysregulation of wild-type p53 is common and supports an MDM2 antagonist as a therapy. RO6839921 is an inactive pegylated prodrug of the oral MDM2 antagonist idasanutlin (active principle [AP]) that allows for IV administration. This phase 1 monotherapy study evaluated the safety, pharmacokinetics, and pharmacodynamics of RO6839921 in patients with AML. Primary objectives identified dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Secondary objectives assessed pharmacokinetic, pharmacodynamic, and antileukemic activity. A total of 26 patients received 120-300 mg AP of idasanutlin. The MTD was 200 mg, with DLTs at 250 (2/8 patients) …

Oral Leukoplakia And Risk Of Progression To Oral Cancer: A Population-Based Cohort Study, Anil K Chaturvedi, Natalia Udaltsova, Eric A Engels, Jed A Katzel, Elizabeth L Yanik, Hormuzd A Katki, Mark W Lingen, Michael J Silverberg

2020-Current year OA Pubs

BACKGROUND: The optimal clinical management of oral precancer remains uncertain. We investigated the natural history of oral leukoplakia, the most common oral precancerous lesion, to estimate the relative and absolute risks of progression to cancer, the predictive accuracy of a clinician's decision to biopsy a leukoplakia vis-à-vis progression, and histopathologic predictors of progression.

METHODS: We conducted a retrospective cohort study (1996-2012) of patients with oral leukoplakia (n = 4886), identified using electronic medical records within Kaiser Permanente Northern California. Among patients with leukoplakia who received a biopsy (n = 1888), we conducted a case-cohort study to investigate histopathologic predictors of …

Five Years Of Ocrelizumab In Relapsing Multiple Sclerosis: Opera Studies Open-Label Extension, Stephen L Hauser, Robert T Naismith, Et Al

Open Access Publications

OBJECTIVE: To assess over 3 years of follow-up the effects of maintaining or switching to ocrelizumab (OCR) therapy on clinical and MRI outcomes and safety measures in the open-label extension (OLE) phase of the pooled OPERA: I/II studies in relapsing multiple sclerosis.

METHODS: After 2 years of double-blind, controlled treatment, patients continued OCR (600 mg infusions every 24 weeks) or switched from interferon (IFN)-β-1a (44 μg 3 times weekly) to OCR when entering the OLE phase (3 years). Adjusted annualized relapse rate, time to onset of 24-week confirmed disability progression (CDP)/improvement (CDP), brain MRI activity (gadolinium-enhanced and new/enlarging T2 lesions), …

Phenotypic Diversity In An International Cure Vcp Disease Registry, Chiseko Ikenaga, Andrew R Findlay, Michelle Seiffert, Allison Peck, Nathan Peck, Nicholas E Johnson, Jeffrey M Statland, Conrad C Weihl

2020-Current year OA Pubs

BACKGROUND: Dominant mutations in valosin-containing protein (VCP) gene cause an adult onset inclusion body myopathy, Paget's disease of bone, and frontotemporal dementia also termed multisystem proteinopathy (MSP). The genotype-phenotype relationships in VCP-related MSP are still being defined; in order to understand this better, we investigated the phenotypic diversity and patterns of weakness in the Cure VCP Disease Patient Registry.

METHODS: Cure VCP Disease, Inc. was founded in 2018 for the purpose of connecting patients with VCP gene mutations and researchers to help advance treatments and cures. Cure VCP Disease Patient Registry is maintained by Coordination of Rare Diseases at Sanford. …

Severe Immunosuppression And Not A Cytokine Storm Characterizes Covid-19 Infections, Kenneth E Remy, Monty Mazer, David A Striker, Ali H Ellebedy, Andrew H Walton, Jacqueline Unsinger, Teresa M Blood, Philip A Mudd, Daehan J Yi, Daniel A Mannion, Dale F Osborne, R Scott Martin, Nitin J Anand, James P Bosanquet, Jane Blood, Anne M Drewry, Charles C Caldwell, Isaiah R Turnbull, Scott C Brakenridge, Lyle L Moldwawer, Richard S Hotchkiss

Open Access Publications

COVID-19-associated morbidity and mortality have been attributed to a pathologic host response. Two divergent hypotheses have been proposed: hyperinflammatory cytokine storm; and failure of host protective immunity that results in unrestrained viral dissemination and organ injury. A key explanation for the inability to address this controversy has been the lack of diagnostic tools to evaluate immune function in COVID-19 infections. ELISpot, a highly sensitive, functional immunoassay, was employed in 27 patients with COVID-19, 51 patients with sepsis, 18 critically ill nonseptic (CINS) patients, and 27 healthy control volunteers to evaluate adaptive and innate immune status by quantitating T cell IFN-ɣ …

Impact Of Annual And Semi-Annual Mass Drug Administration For Lymphatic Filariasis And Onchocerciasis On Hookworm Infection In Côte D'Ivoire, Agodio Loukouri, Aboulaye Méité, Benjamin G. Koudou, Charles W. Goss, Daphne Lew, Gary J. Weil, Eliezer K. N'Goran, Peter U. Fischer

Open Access Publications

Mass Drug Administration (MDA) programs to eliminate Lymphatic Filariasis (LF) in western Africa use the anthelminthics ivermectin plus albendazole. These drugs have the potential to impact also Soil-Transmitted Helminth (STH) infections, since the drugs have a broad range of anthelminthic activity. Integration of preventive chemotherapy efforts for LF, onchocerciasis and STH is recommended by the World Health Organization (WHO) in order to avoid duplication of MDA and to reduce costs. The objective of the current study was to determine whether five semi-annual rounds of community-wide MDA to eliminate LF and onchocerciasis have a greater impact on STH than three annual …

Aadc Deficiency From Infancy To Adulthood: Symptoms And Developmental Outcome In An International Cohort Of 63 Patients, Toni S Pearson, Laura Gilbert, Kathleen D Meeks, Et Al.

2020-Current year OA Pubs

Aromatic l-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive neurodevelopmental disorder characterized by impaired synthesis of dopamine, noradrenaline, adrenaline and serotonin, leading to a complex syndrome of motor, behavioral, and autonomic symptoms. This retrospective study assessed the symptoms and developmental outcome of a large international cohort of patients with AADCD via physician and/or caregiver responses to a detailed, standardized questionnaire. Sixty-three patients (60% female; ages 6 months-36 years, median 7 years; 58 living) from 23 individual countries participated. Common symptoms at onset (median age 3 months, range 0-12 months) were hypotonia, developmental delay, and/or oculogyric crises. Oculogyric crises …

Periacetabular Osteotomy With Or Without Arthroscopic Management In Patients With Hip Dysplasia: Study Protocol For A Multicenter Randomized Controlled Trial, Geoffrey P Wilkin, Stéphane Poitras, John Clohisy, Etienne Belzile, Ira Zaltz, George Grammatopoulos, Gerd Melkus, Kawan Rakhra, Tim Ramsay, Kednapa Thavorn, Paul E Beaulé

2020-Current year OA Pubs

BACKGROUND: Hip dysplasia is one of the most common causes of hip arthritis. Its incidence is estimated to be between 3.6 and 12.8% (Canadian Institute for Health Information, Hip and knee replacements in Canada, 2017-2018: Canadian joint replacement registry annual report, 2019; Jacobsen and Sonne-Holm, Rheumatology 44:211-8, 2004). The Periacetabular Osteotomy (PAO) has been used successfully for over 30 years (Gosvig et al., J Bone Joint Surg Am 92:1162-9, 2010), but some patients continue to exhibit symptoms post-surgery (Wyles et al., Clin Orthop Relat Res 475:336-50, 2017). A hip arthroscopy, performed using a small camera, allows surgeons to address torn …

Diarrhea As A Potential Cause And Consequence Of Reduced Gut Microbial Diversity Among Undernourished Children In Peru, Saba Rouhani, Nicholas W Griffin, Pablo Peñataro Yori, Jeanette L Gehrig, Maribel Paredes Olortegui, Mery Siguas Salas, Dixner Rengifo Trigoso, Lawrence H Moulton, Eric R Houpt, Michael J Barratt, Margaret N Kosek, Jeffrey I Gordon

2020-Current year OA Pubs

BACKGROUND: Detrimental effects of diarrhea on child growth and survival are well documented, but details of the underlying mechanisms remain poorly understood. Recent evidence demonstrates that perturbations to normal development of the gut microbiota in early life may contribute to growth faltering and susceptibility to related childhood diseases. We assessed associations between diarrhea, gut microbiota configuration, and childhood growth in the Peruvian Amazon.

METHODS: Growth, diarrhea incidence, illness, pathogen infection, and antibiotic exposure were assessed monthly in a birth cohort of 271 children aged 0-24 months. Gut bacterial diversity and abundances of specific bacterial taxa were quantified by sequencing 16S …

Safety, Tolerability, And Immunogenicity Of Plasmodium Falciparum Sporozoite Vaccine Administered By Direct Venous Inoculation To Infants And Young Children: Findings From An Age De-Escalation, Dose-Escalation, Double-Blind, Randomized Controlled Study In Western Kenya, Laura C Steinhardt, Ginnie Abarbanell, Et Al.

2020-Current year OA Pubs

BACKGROUND: The whole Plasmodium falciparum sporozoite (PfSPZ) vaccine is being evaluated for malaria prevention. The vaccine is administered intravenously for maximal efficacy. Direct venous inoculation (DVI) with PfSPZ vaccine has been safe, tolerable, and feasible in adults, but safety data for children and infants are limited.

METHODS: We conducted an age de-escalation, dose-escalation randomized controlled trial in Siaya County, western Kenya. Children and infants (aged 5-9 years, 13-59 months, and 5-12 months) were enrolled into 13 age-dose cohorts of 12 participants and randomized 2:1 to vaccine or normal saline placebo in escalating doses: 1.35 × 105, 2.7 × 105, 4.5 …

Gut Microbiota Features Associated With Campylobacter Burden And Postnatal Linear Growth Deficits In A Peruvian Birth Cohort, Saba Rouhani, Nicholas W Griffin, Pablo Peñataro Yori, Maribel Paredes Olortegui, Mery Siguas Salas, Dixner Rengifo Trigoso, Lawrence H Moulton, Eric R Houpt, Michael J Barratt, Margaret N Kosek, Jeffrey I Gordon

2020-Current year OA Pubs

BACKGROUND: Campylobacter infection is associated with impaired growth of children, even in the absence of symptoms. To examine the underlying mechanisms, we evaluated associations between Campylobacter infection, linear growth, and fecal microbial community features in a prospective birth cohort of 271 children with a high burden of diarrhea and stunting in the Amazonian lowlands of Peru.

METHODS: Campylobacter was identified using a broadly reactive, genus-specific enzyme-linked immunosorbent assay. 16S rRNA-based analyses were used to identify bacterial taxa in fecal samples at ages 6, 12, 18, and 24 months (N = 928). Associations between infection, growth, and gut microbial community composition …

The Efficacy Of Lenvatinib Plus Everolimus In Patients With Metastatic Renal Cell Carcinoma Exhibiting Primary Resistance To Front-Line Targeted Therapy Or Immunotherapy, Lana Hamieh, Rachel L Beck, Valerie H Le, James J Hsieh

2020-Current year OA Pubs

BACKGROUND: Patients with primary refractory metastatic renal cell carcinoma (mRCC) have a dismal prognosis and poor response to subsequent treatments. While there are several approved second-line therapies, it remains critical to choose the most effective treatment regimen.

PATIENTS AND METHODS: We identified 7 patients with clear cell mRCC who had primary resistance to vascular endothelial growth factor (VEGF)-targeted tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitor (ICI) combination therapy. The patients were treated with lenvatinib (a multitargeted TKI) plus everolimus (a mammalian target of rapamycin inhibitor). Among these 7 patients, 2 had prior TKI therapy, 3 had prior ICI therapy, …

Combinatorial Pharmacogenomic Algorithm Is Predictive Of Citalopram And Escitalopram Metabolism In Patients With Major Depressive Disorder, Richard C. Shelton, Charles R. Conway, Et Al.

2020-Current year OA Pubs

Pharmacogenomic tests used to guide clinical treatment for major depressive disorder (MDD) must be thoroughly validated. One important assessment of validity is the ability to predict medication blood levels, which reflect altered metabolism. Historically, the metabolic impact of individual genes has been evaluated; however, we now know that multiple genes are often involved in medication metabolism. Here, we evaluated the ability of individual pharmacokinetic genes (CYP2C19, CYP2D6, CYP3A4) and a combinatorial pharmacogenomic test (GeneSight Psychotropic®; weighted assessment of all three genes) to predict citalopram/escitalopram blood levels in patients with MDD. Patients from the Genomics Used to Improve DEpression Decisions (GUIDED) …

The Brief Case: "Not Positive" Or "Not Sure"-Covid-19-Negative Results In A Symptomatic Patient, Bijal A Parikh, Thomas C Bailey, Patrick G Lyons, Neil W Anderson

Open Access Publications

No abstract provided.

Characterization Of A Multicenter Pediatric-Hydrocephalus Shunt Biobank, Jacob Gluski, Paul Zajciw, Prashant Hariharan, Amanda Morgan, Diego M Morales, Andrew Jea, William Whitehead, Neena Marupudi, Steven Ham, Sandeep Sood, James P Mcallister Ii, David D Limbrick Jr, Carolyn A Harris

Open Access Publications

BACKGROUND: Pediatric hydrocephalus is a devastating and costly disease. The mainstay of treatment is still surgical shunting of cerebrospinal fluid (CSF). These shunts fail at a high rate and impose a significant burden on patients, their families and society. The relationship between clinical decision making and shunt failure is poorly understood and multifaceted, but catheter occlusion remains the most frequent cause of shunt complications. In order to investigate factors that affect shunt failure, we have established the Wayne State University (WSU) shunt biobank.

METHODS: To date, four hospital centers have contributed various components of failed shunts and CSF from patients …