Inappropriate Laboratory Testing: Significant Waste Quantified by a Large-Scale Year-Long Study of Medicare and Commercial Payer Reimbursement.

Context.—: Laboratory testing, beyond what is essential for managing health, is considered low-value care, posing patient risks and wasting resources. Measuring excess testing on a national level is crucial to identify waste and optimize healthcare resource allocation for maximum impact.

Structure and Funding of Clinical Informatics Fellowships: A National Survey of Program Directors.

Background: In 2011, the American Board of Medical Specialties established clinical informatics (CI) as a subspecialty in medicine, jointly administered by the American Board of Pathology and the American Board of Preventive Medicine. Subsequently, many institutions created CI fellowship training programs to meet the growing need for informaticists. Although many programs share similar features, there is considerable variation in program funding and administrative structures.

Performance of six SARS-CoV-2 RNA detection systems in symptomatic and asymptomatic pediatric and maternal patients.

This study evaluated the real-world performance of six test systems for detection of SARS-CoV-2 in 138 pediatric and 110 adult maternal patients. Nasopharyngeal swabs were tested directly using the Aptima™ SARS-CoV-2 (Aptima) and Simplexa™ COVID-19 Direct (Simplexa), and with Altona RealStar RT-PCR and CDC RT-PCR with nucleic acid extracted on the Roche MagNA Pure 96 (Altona-MP96) or bioMérieux EMAG (Altona-EMAG). Overall percent-positive and percent-negative agreements among the six test systems were, respectively: Aptima: 94.

Characteristics and Clinical Outcomes of Children and Adolescents Aged <18 Years Hospitalized with COVID-19 - Six Hospitals, United States, July-August 2021.

During June 2021, the highly transmissible B.1.617.

A Daily Operational Huddle and a Real-Time Communication Application Improve Efficiency of Laboratory Processes.

Context.—: Clinical laboratory processes that require cooperation among geographically distinct sections often face challenges. We describe these challenges as related to the Gram staining of cerebrospinal fluid, a key test in the management of patients with suspected central nervous system infections, and our attempts to improve quality outcomes.

Changes in Test Volumes During Coronavirus Disease 2019 (COVID-19): A Laboratory Stewardship Opportunity.

Context.—: Coronavirus disease 2019 (COVID-19) changed the dynamics of health care delivery, shifting patient priorities and deferring care perceived as less urgent. Delayed or eliminated care may place patients at risk for adverse outcomes.

Plasma Metagenomic Next-Generation Sequencing Assay for Identifying Pathogens: a Retrospective Review of Test Utilization in a Large Children's Hospital.

Plasma metagenomic next-generation sequencing (mNGS) is a new diagnostic method used to potentially identify multiple pathogens with a single DNA-based diagnostic test. The test is expensive, and little is understood about where it fits into the diagnostic schema. We describe our experience at Texas Children's Hospital with the mNGS assay by Karius from Redwood City, CA, to determine whether mNGS offers additional diagnostic value when performed within 1 week before or after conventional testing (CT) (i.

The Importance of Genetics Experts in Optimizing Genetic Test Orders Through Prospective and Retrospective Reviews.

Objectives: To demonstrate the impact of genetics specialists on identifying test order errors and improving reimbursement for genetic testing.

Methods: Forty-four cases in which whole exome sequencing (WES) was performed but not reimbursed were reviewed by a genetic counselor through simulated prospective and retrospective reviews.

Results: Fifty-two percent of WES requests were ordered by nongenetics providers.

Transforming Laboratory Utilization Review into Laboratory Stewardship: Guidelines by the PLUGS National Committee for Laboratory Stewardship.

Appropriate utilization of clinical laboratory services is important for patient care and requires institutional stewardship. Clinical laboratory stewardship programs are dedicated to improving the ordering, retrieval, and interpretation of appropriate laboratory tests. In addition, these programs focus on developing, maintaining, and improving systems to provide proper financial coverage for medically necessary testing.

T2Candida Provides Rapid and Accurate Species Identification in Pediatric Cases of Candidemia.

Objectives: The goal of this study is to assess the ability of the T2Candida platform (T2 Biosystems, Lexington, MA) to accurately identify Candida species from pediatric blood specimens with low volumes.

Methods: Whole blood from 15 children with candidemia was collected immediately following blood culture draw. The amount of blood required by the system was reduced by pipetting whole blood directly onto the T2Candida cartridge.

Detecting retroviral sequences in chronic fatigue syndrome.

XMRV or xenotropic murine leukemia virus-related retrovirus, a recently discovered retrovirus, has been linked to both prostate cancer and chronic fatigue syndrome (CFS). Recently, the teams of Drs. Shyh-Ching Lo and Harvey Alter discovered the presence of sequences closely related to XMRV in the blood of 86.

Absence of XMRV retrovirus and other murine leukemia virus-related viruses in patients with chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a multisystem disorder characterized by prolonged and severe fatigue that is not relieved by rest. Attempts to treat CFS have been largely ineffective primarily because the etiology of the disorder is unknown. Recently, CFS has been associated with xenotropic murine leukemia virus-related virus (XMRV) as well as other murine leukemia virus (MLV)-related viruses, though not all studies have found these associations.

Raltegravir is a potent inhibitor of XMRV, a virus implicated in prostate cancer and chronic fatigue syndrome.

Background: Xenotropic murine leukemia-related retrovirus (XMRV) is a recently discovered retrovirus that has been linked to human prostate cancer and chronic fatigue syndrome (CFS). Both diseases affect a large fraction of the world population, with prostate cancer affecting one in six men, and CFS affecting an estimated 0.4 to 1% of the population.

XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors.

Xenotropic murine leukemia virus-related virus (XMRV) was recently discovered in human prostate cancers and is the first gammaretrovirus known to infect humans. While gammaretroviruses have well-characterized oncogenic effects in animals, they have not been shown to cause human cancers. We provide experimental evidence that XMRV is indeed a gammaretrovirus with protein composition and particle ultrastructure highly similar to Moloney murine leukemia virus (MoMLV), another gammaretrovirus.

Mutational analysis of the N-terminal domain of Moloney murine leukemia virus capsid protein.

Retroviral capsid (CA) proteins contain a structurally conserved N-terminal domain (NTD) consisting of a beta-hairpin and six to seven alpha-helices. To examine the role of this domain in Moloney murine leukemia virus (MoMLV) replication, we analyzed 18 insertional mutations in this region. All mutants were noninfectious.

A small loop in the capsid protein of Moloney murine leukemia virus controls assembly of spherical cores.

We report the identification of a novel domain in the Gag protein of Moloney murine leukemia virus (MoLV) that is important for the formation of spherical cores. Analysis of 18 insertional mutations in the N-terminal domain of the capsid protein (CA) identified 3 that were severely defective for viral assembly and release. Transmission electron microscopy of cells producing these mutants showed assembly of Gag proteins in large, flat or dome-shaped patches at the plasma membrane.

Functional analysis of hepatitis C virus envelope proteins, using a cell-cell fusion assay.

Hepatitis C virus (HCV) envelope proteins mediate the entry of virus into cells by binding to cellular receptors, resulting in fusion of the viral membrane with the host cell membrane and permitting the viral genome to enter the cytoplasm. We report the development of a robust and reproducible cell-cell fusion assay using envelope proteins from commonly occurring genotypes of HCV. The assay scored HCV envelope protein-mediated fusion by the production of fluorescent green syncytia and allowed us to elucidate many aspects of HCV fusion, including the pH of fusion, cell types that permit viral entry, and the conformation of envelope proteins essential for fusion.

T-Cell lymphoblastic lymphoma presenting as bilateral multinodular breast masses: a case report and review of the literature.

Non-Hodgkin lymphoma of T-cell lineage involving the breast is rare. We report on a 41-year-old woman with T-cell lymphoblastic lymphoma who presented with multiple bilateral breast masses. The patient was treated with intensive chemotherapy and mediastinal and whole-brain irradiation.

Comprehensive mutational analysis of a herpesvirus gene in the viral genome context reveals a region essential for virus replication.

Essential viral proteins perform vital functions during morphogenesis via a complex interaction with other viral and cellular gene products. Here, we present a novel approach to comprehensive mutagenesis of essential cytomegalovirus genes and biological analysis in the 230-kbp-genome context. A random Tn7-based mutagenesis procedure at the single-gene level was combined with site-specific recombination via the FLP/FLP recognition target site system for viral genome reconstitution.

Functional characterization of a portion of the Moloney murine leukemia virus gag gene by genetic footprinting.

Retroviral Gag proteins perform important functions in viral assembly, but are also involved in other steps in the viral life cycle. Conventional mutational analysis has yielded considerable information about domains essential for these functions, yet many regions of gag remain uncharacterized. We used genetic footprinting, a technique that permits the generation and simultaneous analysis of large numbers of mutations, to perform a near-saturation mutagenesis and functional analysis of 639 nucleotides in the gag region of Moloney murine leukemia virus.

Genetic footprinting of the HIV co-receptor CCR5: delineation of surface expression and viral entry determinants.

Human immunodeficiency virus type 1 (HIV-1) utilizes CD4 as a primary receptor for viral entry and any of several 7-transmembrane chemokine receptors, including CCR5, as a co-receptor. Previous studies have demonstrated that multiple extracellular domains (ECDs) of CCR5 contribute to co-receptor function; here we applied genetic footprinting to CCR5 to confirm and extend those investigations. In genetic footprinting, a duplex oligonucleotide is inserted into the DNA sequence of interest by use of either a bacterial transposase or retroviral integrase.