Medicine and Health Sciences Commons^™

Priorities To Promote Participant Engagement In The Participant Engagement And Cancer Genome Sequencing (Pe-Cgs) Network, Anne Lr Schuster, Graham A Colditz, Li Ding, Bettina F Drake, Ryan C Fields, Et Al.

2020-Current year OA Pubs

BACKGROUND: Engaging diverse populations in cancer genomics research is of critical importance and is a fundamental goal of the NCI Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network. Established as part of the Cancer Moonshot, PE-CGS is a consortium of stakeholders including clinicians, scientists, genetic counselors, and representatives of potential study participants and their communities. Participant engagement is an ongoing, bidirectional, and mutually beneficial interaction between study participants and researchers. PE-CGS sought to set priorities in participant engagement for conducting the network's research.

METHODS: PE-CGS deliberatively engaged its stakeholders in the following four-phase process to set the network's research priorities …

On-The-Go Adaptation Of Implementation Approaches And Strategies In Health: Emerging Perspectives And Research Opportunities, Elvin H Geng, Aaloke Mody, Byron J Powell

2020-Current year OA Pubs

In many cases, implementation approaches (composed of one or more strategies) may need to change over time to work optimally. We use a literature review to inform a mechanistic analysis of such on-the-go adaptations. We suggest that such adaptations of implementation strategies consist of three necessary steps. The first component is the initial effect of the implementation approach on intended implementation, service delivery, or clinical outcomes. Second, these initial effects must in turn be used to modify, alter, intensify, or otherwise change the implementation approach. Third, the modified approach itself has effects. Conceiving of adaptation as all three steps implies …

Advanced Care Planning For Hospitalized Patients Following Clinician Notification Of Patient Mortality By A Machine Learning Algorithm, Stephen Chi, Seunghwan Kim, Matthew Reuter, Katharine Ponzillo, Debra Parker Oliver, Randi Foraker, Kevin Heard, Jingxia Liu, Kyle Pitzer, Patrick White, Nathan Moore

2020-Current year OA Pubs

IMPORTANCE: Goal-concordant care is an ongoing challenge in hospital settings. Identification of high mortality risk within 30 days may call attention to the need to have serious illness conversations, including the documentation of patient goals of care.

OBJECTIVE: To examine goals of care discussions (GOCDs) in a community hospital setting with patients identified as having a high risk of mortality by a machine learning mortality prediction algorithm.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study took place at community hospitals within 1 health care system. Participants included adult patients with a high risk of 30-day mortality who were admitted to 1 …

Estimated Clinical Outcomes And Cost-Effectiveness Associated With Provision Of Addiction Treatment In Us Primary Care Clinics, Raagini Jawa, Yjuliana Tin, Samantha Nall, Susan L Calcaterra, Alexandra Savinkina, Laura R Marks, Simeon D Kimmel, Benjamin P Linas, Joshua A Barocas

2020-Current year OA Pubs

IMPORTANCE: US primary care practitioners (PCPs) are the largest clinical workforce, but few provide addiction care. Primary care is a practical place to expand addiction services, including buprenorphine and harm reduction kits, yet the clinical outcomes and health care sector costs are unknown.

OBJECTIVE: To estimate the long-term clinical outcomes, costs, and cost-effectiveness of integrated buprenorphine and harm reduction kits in primary care for people who inject opioids.

DESIGN, SETTING, AND PARTICIPANTS: In this modeling study, the Reducing Infections Related to Drug Use Cost-Effectiveness (REDUCE) microsimulation model, which tracks serious injection-related infections, overdose, hospitalization, and death, was used to examine …

Rapid Profiling Of Dna Replication Dynamics Using Mass Spectrometry-Based Analysis Of Nascent Dna, Mohamed E Ashour, Andrea K Byrum, Alice Meroni, Jun Xia, Saurabh Singh, Roberto Galletto, Susan M Rosenberg, Alessandro Vindigni, Nima Mosammaparast

2020-Current year OA Pubs

The primary method for probing DNA replication dynamics is DNA fiber analysis, which utilizes thymidine analog incorporation into nascent DNA, followed by immunofluorescent microscopy of DNA fibers. Besides being time-consuming and prone to experimenter bias, it is not suitable for studying DNA replication dynamics in mitochondria or bacteria, nor is it adaptable for higher-throughput analysis. Here, we present mass spectrometry-based analysis of nascent DNA (MS-BAND) as a rapid, unbiased, quantitative alternative to DNA fiber analysis. In this method, incorporation of thymidine analogs is quantified from DNA using triple quadrupole tandem mass spectrometry. MS-BAND accurately detects DNA replication alterations in both …

The Value And Impacts Of Academic Public Health Departments, Paul C Erwin, Julie H Grubaugh, Stephanie Mazzucca-Ragan, Ross C Brownson

2020-Current year OA Pubs

The academic health department (AHD) is a partnership between an academic institution and a governmental health agency. These partnerships are meant to provide mutual benefits that include opportunities for student field placements and internships, practice-informed curriculum, and practice-based research. The term academic health department dates back only to 2000, although there are several examples of academic-practice partnerships prior to that date. In addition to AHDs that have been established over the past two decades, other forms of academic-practice engagement provide similar mutual benefits, such as prevention research centers and public health training centers. Current research on AHDs explores how these …

Utilization Of Microwave Ablation As A Novel Approach For Refractory Chylothorax Following Esophagectomy: A Case Report, Khashayar Farahnak, Alejandro De Filippis Falcon, Hailey M Shepherd, Carlos J Guevara, Mayank R Patel, G Alexander Patterson, Varun Puri, Daniel Kreisel, Ruben G Nava

2020-Current year OA Pubs

No abstract provided.

Logistical, Technical, And Radiation Safety Aspects Of Establishing A Radiopharmaceutical Therapy Program: A Case In Lutetium-177 Prostate-Specific Membrane Antigen (Psma) Therapy, Jacqueline E Zoberi, Jose Garcia-Ramirez, David Luechtefeld, Nichole M Maughan, Maxwell Amurao, Reiko Oyama, Brian C Baumann, Hiram A Gay, Jeff M Michalski

2020-Current year OA Pubs

Prostate-specific membrane antigen (PSMA) is a cell surface protein highly expressed in nearly all prostate cancers, with restricted expression in some normal tissues. The differential expression of PSMA from tumor to non-tumor tissue has resulted in the investigation of numerous targeting strategies for therapy of patients with metastatic prostate cancer. In March of 2022, the FDA granted approval for the use of lutetium-177 PSMA-617 (Lu-177-PSMA-617) for patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. Therefore, the use of Lu-177-PSMA-617 is expected to increase and become more widespread. Herein, …

Management Of Infusion-Related Reactions (Irrs) In Patients Receiving Amivantamab In The Chrysalis Study, Keunchil Park, Ramaswamy Govindan, Et Al.

2020-Current year OA Pubs

BACKGROUND: Amivantamab, a fully humanized EGFR-MET bispecific antibody, has antitumor activity in diverse EGFR- and MET-driven non-small cell lung cancer (NSCLC) and a safety profile consistent with associated on-target activities. Infusion-related reaction(s) (IRR[s]) are reported commonly with amivantamab. We review IRR and subsequent management in amivantamab-treated patients.

METHODS: Patients treated with the approved dose of intravenous amivantamab (1050 mg, <80 kg; 1400 mg, ≥80 kg) in CHRYSALIS-an ongoing, phase 1 study in advanced EGFR-mutated NSCLC-were included in this analysis. IRR mitigations included split first dose (350 mg, day 1 [D1]; remainder, D2), reduced initial infusion rates with proactive infusion interruption, and steroid premedication before initial dose. For all doses, pre-infusion antihistamines and antipyretics were required. Steroids were optional after the initial dose.

RESULTS: As of 3/30/2021, 380 patients received amivantamab. IRRs were reported in 256 (67%) patients. Signs/symptoms of IRR included chills, dyspnea, flushing, nausea, chest discomfort, and vomiting. Most of the 279 IRRs were grade 1 or 2; grade 3 and 4 …

Mitochondrial Pyruvate Carrier Inhibition Initiates Metabolic Crosstalk To Stimulate Branched Chain Amino Acid Catabolism, Daniel Ferguson, Sophie J Eichler, Nicole K H Yiew, Jerry R Colca, Kevin Cho, Gary J Patti, Trevor M Shew, Andrew J Lutkewitte, Sandip Mukherjee, Kyle S Mccommis, Natalie M Niemi, Brian N Finck

2020-Current year OA Pubs

OBJECTIVE: The mitochondrial pyruvate carrier (MPC) has emerged as a therapeutic target for treating insulin resistance, type 2 diabetes, and nonalcoholic steatohepatitis (NASH). We evaluated whether MPC inhibitors (MPCi) might correct impairments in branched chain amino acid (BCAA) catabolism, which are predictive of developing diabetes and NASH.

METHODS: Circulating BCAA concentrations were measured in people with NASH and type 2 diabetes, who participated in a recent randomized, placebo-controlled Phase IIB clinical trial to test the efficacy and safety of the MPCi MSDC-0602K (EMMINENCE; NCT02784444). In this 52-week trial, patients were randomly assigned to placebo (n = 94) or 250 mg …

Presentation And Prognosis Of Excessive Asymptomatic Atrial Ectopy In Children And Adolescents With Structurally And Functionally Normal Hearts, Thomas R Joyce, James J Joyce, Marye J Gleva, Sunita J Ferns

2020-Current year OA Pubs

Excessive premature atrial complexes (PACs) in pediatric patients with a structurally normal heart are presumed to be benign and self-resolving, but no studies have confirmed this. Adults with excessive PACs, however, are at increased risk for future sustained atrial arrhythmias and cardiovascular morbidity and mortality. Therefore, we sought to evaluate the clinical course of frequent PACs in asymptomatic children. Patients < 21 years old with numerous asymptomatic PACs (>50/24 hours) were retrospectively selected over a 10-year period. Demographics, clinical characteristics, and results of cardiovascular testing were tabulated. Two groups were defined: those with a significant (>20%) reduction in burden of atrial ectopy versus those with an insignificant …

Translingual Neurostimulation Combined With Physical Therapy To Improve Walking And Balance In Multiple Sclerosis (Neuromstrals): Study Protocol For A Randomized Controlled Trial, Michelle Ploughman, Ganeswara Rao Melam, Syamala Buragadda, Keith R Lohse, Fraser Clift, Mark Stefanelli, Michael Levin, Sarah J Donkers

2020-Current year OA Pubs

INTRODUCTION: Physical rehabilitation restores lost function and promotes brain plasticity in people with Multiple Sclerosis (MS). Research groups worldwide are testing the therapeutic effects of combining non-invasive neuromodulation with physical therapy (PT) to further improve functional outcomes in neurological disorders but with mixed results. Whether such devices enhance function is not clear. We present the rationale and study design for a randomized controlled trial evaluating if there is additional benefit to the synergistic pairing of translingual neurostimulation (TLNS) with PT to improve walking and balance in MS.

METHODS AND ANALYSIS: A parallel group [PT + TLNS or PT + Sham], …

Using Synthetic Mr Images For Distortion Correction, David F Montez, Andrew N Van, Ryland L Miller, Nicole A Seider, Scott Marek, Annie Zheng, Dillan J Newbold, Kristen Scheidter, Benjamin P Kay, Abhinav K Jha, Aristeidis Sotiras, Timothy O Laumann, Evan M Gordon, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Functional MRI (fMRI) data acquired using echo-planar imaging (EPI) are highly distorted by magnetic field inhomogeneities. Distortion and differences in image contrast between EPI and T1-weighted and T2-weighted (T1w/T2w) images makes their alignment a challenge. Typically, field map data are used to correct EPI distortions. Alignments achieved with field maps can vary greatly and depends on the quality of field map data. However, many public datasets lack field map data entirely. Additionally, reliable field map data is often difficult to acquire in high-motion pediatric or developmental cohorts. To address this, we developed Synth, a software package for distortion correction and …

Expanding The Muscle Imaging Spectrum In Dysferlinopathy: Description Of An Outlier Population From The Classical Mri Pattern, Laura Llansó, Alan Pestronk, Et Al.

2020-Current year OA Pubs

Dysferlinopathy is a muscle disease characterized by a variable clinical presentation and is caused by mutations in the DYSF gene. The Jain Clinical Outcome Study for Dysferlinopathy (COS) followed the largest cohort of patients (n=187) with genetically confirmed dysferlinopathy throughout a three-year natural history study, in which the patients underwent muscle function tests and muscle magnetic resonance imaging (MRI). We previously described the pattern of muscle pathology in this population and established a series of imaging criteria for diagnosis. In this paper, we describe the muscle imaging and clinical features of a subgroup of COS participants whose muscle imaging results …

Outcome Prediction By The 2022 European Leukemianet Genetic-Risk Classification For Adults With Acute Myeloid Leukemia: An Alliance Study, Krzysztof Mrózek, Geoffrey L Uy, Et Al.

2020-Current year OA Pubs

Recently, the European LeukemiaNet (ELN) revised its genetic-risk classification of acute myeloid leukemia (AML). We categorized 1637 adults with AML treated with cytarabine/anthracycline regimens according to the 2022 and 2017 ELN classifications. Compared with the 2017 ELN classification, 2022 favorable group decreased from 40% to 35% and adverse group increased from 37% to 41% of patients. The 2022 genetic-risk groups seemed to accurately reflect treatment outcomes in all patients and patients aged <60 years, but in patients aged ≥60 years, relapse rates, disease-free (DFS) and overall (OS) survival were not significantly different between intermediate and adverse groups. In younger African-American patients, DFS and OS did not differ between intermediate-risk and adverse-risk patients nor did DFS between favorable and intermediate groups. In Hispanic patients, DFS and OS did not differ between favorable and intermediate groups. Outcome prediction abilities of 2022 and 2017 ELN classifications were similar. Among favorable-risk patients, myelodysplasia-related mutations did not affect patients with CEBPA

Social Disadvantage During Pregnancy: Effects On Gestational Age And Birthweight, Joan L Luby, Sarah K England, Deanna M Barch, Barbara B Warner, Cynthia Rogers, Christopher D Smyser, Regina Triplett, Jyoti Arora, Tara A Smyser, George M Slavich, Peinan Zhao, Molly Stout, Erik Herzog, J Philip Miller

2020-Current year OA Pubs

OBJECTIVE: Whether psychosocial adversity during pregnancy impacts fetal health outcomes at birth remains underexplored. This is a critical issue given significant social disadvantage and psychosocial stress faced by pregnant women worldwide.

STUDY DESIGN: Measures of social disadvantage and psychological factors, and medical/reproductive and nutritional health status in pregnant women were obtained at each trimester. Using Structural Equation Modeling (SEM), we investigated the relationship of forms of adversity to each other and to infant gestational age, and birthweight.

RESULTS: Among 399 singletons, Social Disadvantage significantly predicted gestational age (p = 0.003), and residual birthweight (p = 0.006). There was a 0.4 …

Understanding Misimplementation In U.S. State Health Departments: An Agent-Based Model, Matt Kasman, Ross A Hammond, Rob Purcell, Louise Farah Saliba, Stephanie Mazzucca-Ragan, Margaret Padek, Peg Allen, Douglas A Luke, Sarah Moreland-Russell, Paul C Erwin, Ross C Brownson

2020-Current year OA Pubs

INTRODUCTION: The research goal of this study is to explore why misimplementation occurs in public health agencies and how it can be reduced. Misimplementation is ending effective activities prematurely or continuing ineffective ones, which contributes to wasted resources and suboptimal health outcomes.

METHODS: The study team created an agent-based model that represents how information flow, filtered through organizational structure, capacity, culture, and leadership priorities, shapes continuation decisions. This agent-based model used survey data and interviews with state health department personnel across the U.S. between 2014 and 2020; model design and analyses were conducted with substantial input from stakeholders between 2019 …

Air Pollution And Acute Kidney Injury In The U.S. Medicare Population: A Longitudinal Cohort Study, Whanhee Lee, Ziyad Al-Aly, Et Al.

2020-Current year OA Pubs

BACKGROUND: Recent studies have reported the association between air pollution exposure and reduced kidney function. However, it is unclear whether air pollution is associated with an increased risk of acute kidney injury (AKI).

OBJECTIVES: To address this gap in knowledge, we investigated the effect estimates of long-term exposures to fine particulate matter [PM

METHODS: This nationwide population-based longitudinal cohort study included 61,300,754 beneficiaries enrolled in Medicare Part A fee-for-service (FFS) who were

RESULTS: Exposure to

DISCUSSION: This study found an association between exposures to air pollution and the risk of the first hospital admission with AKI, and this association persisted …

Myeloid Autophagy Genes Protect Mice Against Fatal Tnf- And Lps-Induced Cytokine Storm Syndromes, Ya-Ting Wang, Amy Sansone, Asya Smirnov, Christina L Stallings, Anthony Orvedahl

2020-Current year OA Pubs

ATG5: autophagy related 5; ATG7: autophagy related 7; ATG14: autophagy related 14; ATG16L1: autophagy related 16-like 1 (S. cerevisiae); BECN1: beclin 1, autophagy related; CASP1: caspase 1; CASP4/CASP11: caspase 4, apoptosis-related cysteine peptidase; CIM: conditionally immortalized macrophage; CLP: cecal ligation and puncture; CSS: cytokine storm syndrome; DC: dendritic cell; IFNG/IFNγ: interferon gamma; IFNGR1: interferon gamma receptor 1; ip: intraperitoneal; iv: intravenous; IL12/p70: interleukin 12, p70 heterodimer; IL18: Interleukin 18; ITGAX/CD11c: integrin alpha X; LAP: LC3-associated phagocytosis; LPS: lipopolysaccharide; LYZ2/LYSM: lysozyme 2; MAP1LC3A/LC3: microtubule-associated protein 1 light chain 3 alpha; RB1CC1/FIP200: RB1-inducible coiled-coil 1; S100A8/MRP8: S100 calcium binding protein A8 (calgranulin …

Complete Remission Of Widely Metastatic Human Epidermal Growth Factor Receptor 2-Amplified Pancreatic Adenocarcinoma After Precision Immune And Targeted Therapy With Description Of Sequencing And Organoid Correlates, Daniel A King, S Peter Goedegebuure, Xiuli Zhang, Jasreet Hundal, Malachi Griffith, William E Gillanders, Haeseong Park, Et Al.

2020-Current year OA Pubs

No abstract provided.

Persistent Molecular Disease In Adult Patients With Aml Evaluated With Whole-Exome And Targeted Error-Corrected Dna Sequencing, Michael J Slade, Reza Ghasemi, Michelle O'Laughlin, Tasha Burton, Robert S Fulton, Haley J Abel, Eric J Duncavage, Timothy J Ley, Meagan A Jacoby, David H Spencer

2020-Current year OA Pubs

PURPOSE: Persistent molecular disease (PMD) after induction chemotherapy predicts relapse in AML. In this study, we used whole-exome sequencing (WES) and targeted error-corrected sequencing to assess the frequency and mutational patterns of PMD in 30 patients with AML.

MATERIALS AND METHODS: The study cohort included 30 patients with adult AML younger than 65 years who were uniformly treated with standard induction chemotherapy. Tumor/normal WES was performed for all patients at presentation. PMD analysis was evaluated in bone marrow samples obtained during clinicopathologic remission using repeat WES and analysis of patient-specific mutations and error-corrected sequencing of 40 recurrently mutated AML genes …

Circadian Rhythm Disrupting Behaviours And Cancer Outcomes In Breast Cancer Survivors: A Systematic Review, Kelly D'Cunha, Yikyung Park, Melinda M Protani, Marina M Reeves

2020-Current year OA Pubs

PURPOSE: Circadian rhythm disruptors (e.g., night-shift work) are risk factors for breast cancer, however studies on their association with prognosis is limited. A small but growing body of research suggests that altered sleep patterns and eating behaviours are potential mechanistic links between circadian rhythm disruptors and breast cancer. We therefore systematically summarised literature examining the influence of circadian rhythm disrupting behaviours on cancer outcomes in women with breast cancer.

METHODS: A systematic search of five databases from inception to January 2021 was conducted. Original research published in English, assessing the relationship between post-diagnosis sleep patters and eating behaviours, and breast …

Baseline Characteristics Of The North American Prodromal Synucleinopathy Cohort, Jonathan E Elliott, Jennifer Mcleland, Susan R Criswell, Yo-El S Ju, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Rapid eye movement (REM) sleep behavior disorder (RBD) is widely considered a prodromal synucleinopathy, as most with RBD develop overt synucleinopathy within ~10 years. Accordingly, RBD offers an opportunity to test potential treatments at the earliest stages of synucleinopathy. The North American Prodromal Synucleinopathy (NAPS) Consortium has created a multisite RBD participant, primarily clinic-based cohort to better understand characteristics at diagnosis, and in future work, identify predictors of phenoconversion, develop synucleinopathy biomarkers, and enable early stage clinical trial enrollment.

METHODS: Participants ≥18 years of age with overnight polysomnogram-confirmed RBD without Parkinson's disease, dementia, multiple system atrophy, or narcolepsy were …

Is Local Review Of Positron Emission Tomography Scans Sufficient In Diffuse Large B-Cell Lymphoma Clinical Trials? A Calgb 50303 Analysis, Pallawi Torka, Levi D Pederson, Michael V Knopp, David Poon, Jun Zhang, Brad S Kahl, Howard R Higley, Gary Kelloff, Jonathan W Friedberg, Lawrence H Schwartz, Wyndham H Wilson, John P Leonard, Nancy L Bartlett, Heiko Schöder, Amy S Ruppert

2020-Current year OA Pubs

BACKGROUND: Quantitative methods of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) interpretation, including the percent change in FDG uptake from baseline (ΔSUV), are under investigation in lymphoma to overcome challenges associated with visual scoring systems (VSS) such as the Deauville 5-point scale (5-PS).

METHODS: In CALGB 50303, patients with DLBCL received frontline R-CHOP or DA-EPOCH-R, and although there were no significant associations between interim PET responses assessed centrally after cycle 2 (iPET) using 5-PS with progression-free survival (PFS) or overall survival (OS), there were significant associations between central determinations of iPET ∆SUV with PFS/OS. In this patient cohort, we retrospectively compared local …

Lrp6 High Bone Mass Characterized In Two Generations Harboring A Unique Mutation Of Low-Density Lipoprotein Receptor-Related Protein 6, Michael P Whyte, Steven Mumm, Jonathan C Baker, Fan Zhang, Homer Sedighi, Shenghui Duan, Tim Cundy

2020-Current year OA Pubs

Osteoblast Wnt/

Area Deprivation Index And Segregation On The Risk Of Hiv: A U.S. Veteran Case-Control Study, Abiodun O Oluyomi, Angela L Mazul, Yongquan Dong, Donna L White, Christine M Hartman, Peter Richardson, Wenyaw Chan, Jose M Garcia, Jennifer R Kramer, Elizabeth Chiao

2020-Current year OA Pubs

BACKGROUND: Preventing HIV infection remains a critically important tool in the continuing fight against HIV/AIDS. The primary aim is to evaluate the effect and interactions between a composite area-level social determinants of health measure and an area-level measure of residential segregation on the risk of HIV/AIDS in U.S. Veterans.

METHODS: Using the individual-level patient data from the U.S. Department of Veterans Affairs, we constructed a case-control study of veterans living with HIV/AIDS (VLWH) and age-, sex assigned at birth- and index date-matched controls. We geocoded patient's residential address to ascertain their neighborhood and linked their information to two measures of …

The Next Phase In Patient Safety Education: Towards A Standardized, Tools-Based Pathology Patient Safety Curriculum: A Call To Action From The Association Of Pathology Chairs' Residency Program Directors Section Training Residents In Patient Safety Workgroup, Cynthia K Harris, Ronald Jackups Jr, Et Al.

2020-Current year OA Pubs

Patient safety education is a mandated Common Program Requirement of the Accreditation Council for Graduate Medical Education and for the Royal College of Physicians and Surgeons of Canada in all medical residency and fellowship programs. Although many hospitals and healthcare environments have general patient safety education tools for trainees, few to none focus on the unique training milieu of pathologists, including a mix of highly automated and manual error-prone processes, frequent multiplicity of events, and lack of direct patient relationships for error disclosure. We established a national Association of Pathology Chairs-Program Directors Section Workgroup focused on patient safety education for …

The Who Aware (Access, Watch, Reserve) Antibiotic Book And Prevention Of Antimicrobial Resistance, Veronica Zanichelli, Michael Sharland, Bernadette Cappello, Lorenzo Moja, Haileyesus Getahun, Carmem Pessoa-Silva, Hatim Sati, Catharina Van Weezenbeek, Hanan Balkhy, Mariângela Simão, Sumanth Gandra, Benedikt Huttner

2020-Current year OA Pubs

Guidance on the appropriate use of antibiotics for common infections is lacking in many settings. The World Health Organization (WHO) has recently released

Axatilimab For Chronic Graft-Versus-Host Disease After Failure Of At Least Two Prior Systemic Therapies: Results Of A Phase I/Ii Study, Carrie L Kitko, Iskra Pusic, Et Al.

2020-Current year OA Pubs

PURPOSE: Chronic graft-versus-host disease (cGVHD) remains the major cause of late morbidity after allogeneic hematopoietic cell transplantation. Colony-stimulating factor 1 receptor (CSF-1R)-dependent macrophages promote cGVHD fibrosis, and their elimination in preclinical studies ameliorated cGVHD. Axatilimab is a humanized monoclonal antibody that inhibits CSF-1R signaling and restrains macrophage development.

PATIENTS AND METHODS: This phase I (phI)/phase II (phII) open-label study (ClinicalTrials.gov identifier: NCT03604692) evaluated safety, tolerability, and efficacy of axatilimab in patients age ≥ 6 years with active cGVHD after ≥ 2 prior systemic therapy lines. Primary objectives in phI were to identify the optimal biologic and recommended phII dose and …

Insights Into The Pathogenesis Of Hereditary Angioedema Using Genetic Sequencing And Recombinant Protein Expression Analyses, Zhen Ren, Shuangxia Zhao, Tiandao Li, H James Wedner, John P Atkinson

2020-Current year OA Pubs

BACKGROUND: The pathogenesis of hereditary angioedema (HAE) type I and type II is linked to defective C1 esterase inhibitor (C1-INH) encoded by the SERPING1 gene. There are substantial variabilities in the clinical presentations of patients with HAE that are not directly correlated to the serum levels of C1-INH. The impact of SERPING1 variants on C1-INH expression, structure, and function is incompletely understood.

OBJECTIVE: To investigate the influence of SERPING1 variants on the C1-INH expression, structure, and function of 20 patients with HAE from 14 families with no prior genetic diagnosis.

METHODS: Patients underwent whole-exome sequencing (WES). If no variants were …