Reduced Likelihood of Hospitalization With the JN.1 or HV.1 Severe Acute Respiratory Syndrome Coronavirus 2 Variants Compared With the EG.5 Variant.

Within a multistate viral genomic surveillance program, we evaluated whether proportions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections attributed to the JN.1 variant and to XBB-lineage variants (including HV.1 and EG.

Liquid Biopsy for Advanced Cancer: An Amplicon-Based Massively Parallel Sequencing Panel Approach to Precision Oncology.

Although discovered in the 1940s (Mandel and Metais, C R Seances Soc Biol Fil 142:241-243, 1948), cell-free DNA has only recently become a tool practical for use in clinical settings. The challenges associated with detection of circulating tumor DNA (ctDNA) in patient plasma are many and exist in the pre-analytical, analytical, and post-analytical periods. Initiation of a ctDNA program in a small academic clinical laboratory setting can be challenging.

Next-Generation Sequencing Informatic Architecture Considerations.

Clinically relevant sequencing methodologies continue to expand in number, diversity, complexity, and scale. This evolving and varied landscape requires unique implementations in all aspects of the assay, including the wet bench, bioinformatics, and reporting. Following implementation, the informatics of many of these tests continue to change over time, from software and annotation source updates, guidelines, and knowledgebase changes to changes in underlying information technology (IT) infrastructure.

Managing a PCR Contamination Event in a Molecular Pathology Laboratory.

Contamination in a molecular laboratory may lead to erroneous results with potential to cause patient harm if not promptly identified and corrected. A general overview of the practices used in molecular laboratories to identify and address contamination once an event has occurred is discussed. The process used to assess the risk associated with the identified contamination event, determine the appropriate course of immediate action, perform a root cause analysis to determine the source of contamination, and assess and document the results of the decontamination process will be reviewed.

Novel high-risk acute myeloid leukemia subgroup with ERG amplification and Biallelic loss of TP53.

ETS-related gene (ERG) amplification, observed in 4-6% of acute myeloid leukemia (AML), is associated with unfavorable prognosis. To determine coincident effects of additional genomic abnormalities in AML with ERG amplification (ERGamp), we examined 11 ERGamp cases of 205 newly diagnosed AML using chromosomal microarray analysis and next generation sequencing. ERGamp cases demonstrated a distinct pattern of high genetic complexity: loss of 5q, chromothripsis and TP53 loss of function variants.

Clinical utility of chromosomal microarray in establishing clonality and high risk features in patients with Richter transformation.

Richter transformation (RT) refers to the development of an aggressive lymphoma in patients with pre-existing chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). It carries a poor prognosis secondary to poor response to therapy or rapid disease relapse. Currently there are no randomized trials to guide treatment.

Integrated genomic analysis using chromosomal microarray, fluorescence in situ hybridization and mate pair analyses: Characterization of a cryptic t(9;22)(p24.1;q11.2)/BCR-JAK2 in myeloid/lymphoid neoplasm with eosinophilia.

The 2016 World Health Organization entity 'Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1, or with PCM1-JAK2' encompasses a group of rare neoplasms that result from the formation of a fusion gene that leads to expression of an aberrant tyrosine kinase. This entity also contains variant JAK2 fusion partners, and detection of this defining event can be facilitated by various cytogenetic and molecular methods. Cryptic rearrangements of 9p24/JAK2 can be particularly challenging to identify.

Molecular profiling of vitreous fluid by massively parallel sequencing: a case series.

Introduction: In cases of suspected intraocular malignancy, vitreous may be the preferred pathologic sample; however, cellularity may be insufficient for definitive cytopathological diagnosis. Ancillary methodology to study vitreous fluid aspiration for mutational analysis may assist in treatment decisions.

Materials And Methods: Three individual patient vitreous humor samples were received in the laboratory for mutation testing.

Cryptic and atypical KMT2A-USP2 and KMT2A-USP8 rearrangements identified by mate pair sequencing in infant and childhood leukemia.

Infant leukemias are a rare group of neoplasms that are clinically and biologically distinct from their pediatric and adult counterparts. Unlike leukemia in older children where survival rates are generally favorable, infants with leukemia have a 5-year event-free survival rate of <50%. The majority of infant leukemias are characterized by KMT2A (MLL) rearrangements (~70 to 80% in acute lymphoblastic leukemia), which appear to be drivers of early leukemogenesis.

Glycogen Storage Disease Type IV Diagnosed at Fetal Autopsy.

Glycogen storage disease type IV (GSD IV; Andersen's disease) is a rare autosomal recessive disorder that results from defects in the gene (3p12.2) and subsequent deficiencies of glycogen branching. We report a case of GSD IV diagnosed at autopsy in a 35 4/7 weeks gestational age female neonate that died shortly after birth.

Aqueous Fluid as a Viable Substitute for Vitreous Fluid in Postmortem Chemistry Analysis.

Vitreous fluid sampling for postmortem chemistry analysis is discouraged in pediatric forensic cases involving head trauma due to the risk of introducing retinal artifacts. Aqueous fluid is physically separated from the posterior chamber of the eye, and therefore, unlikely to produce vitreal artifact when sampled. Analysis of aqueous fluid is therefore proposed as a substitute for vitreous.

Maternal Epidural Steroids to Prevent Neonatal Exposure to Hyperthermia and Inflammation.

Background: Epidural analgesia is associated with a fourfold increased rate of intrapartum fever. The likely pathophysiology is a noninfectious maternal inflammatory activation. Safe interventions to reduce maternal and neonatal exposures to intrapartum fever and inflammation are needed.

Benign Fibromyxoid Lesion of the Breast: A Distinct Entity From Benign Spindle Cell Tumors of the Mammary Stroma?

Myxoid lesions of the breast can be diagnostically challenging entities. We report 4 cases of CD34+ fibromyxoid lesion that have been previously diagnosed as "benign myxoid lesion," "nodular mucinosis," or "mammary myofibroblastoma, myxoid type" on the basis of CD34-positivity. The lesions were microscopically well circumscribed and composed of a paucicellular spindle cell proliferation in a background of myxoid stroma.

First Report of Prenatal Ascertainment of a Fetus With Homozygous Loss of the SOX10 Gene and Phenotypic Correlation by Autopsy Examination.

The SOX10 gene plays a vital role in neural crest cell development and migration. Abnormalities in SOX10 are associated with Waardenburg syndrome Types II and IV, and these patients have recognizable clinical features. This case report highlights the first ever reported homozygous loss of function of the SOX10 gene in a human.

IgM Myeloma with Plasma Cell Leukemia: Case Report and Literature Review.

IgM multiple myeloma (MM) is a rare entity representing approximately 0.5% of all MM. It should be distinguished from malignant neoplasms of B cells with plasmacytic differentiation such as Waldenstrom macroglobulinemia (WM) and marginal zone lymphoma with plasmacytic differentiation.

Use of an Automated Nested Multiplex Respiratory Pathogen PCR Panel Postmortem in the Pediatric Forensic Setting.

Respiratory pathogens have been detected in forensic investigations using multiple techniques; however, no study has examined the use of automated, nested, multiplex polymerase chain reaction (ANM-PCR), commonly used in living patients, in the forensic setting. This retrospective study assessed the utility of ANM-PCR in detecting respiratory pathogens in the pediatric forensic setting. Respiratory samples from 35 cases were tested for up to 20 respiratory pathogens.

Urothelial carcinoma of donor origin in a kidney transplant patient.

Background: Malignancy after transplantation is an uncommon multifactorial occurrence. Immunosuppression to prevent graft rejection is described as a major risk factor in malignancy development in the post-transplant state. Donor-derived malignancy is a rare reported complication.

Amyloidosis and Unexpected Death: A Review of Seven Cases.

Amyloidosis, deposition of improperly folded insoluble proteins, may affect one organ or may be systemic. Although plasma cell dyscrasia is frequently implicated in etiology and is due to immunoglobulin light chain production (AL amyloidosis), age-related amyloidosis is believed to be secondary to transthyretin production (ATTR), chronic inflammation-related amyloidosis is thought due to acute phase reactants (AA amyloidosis), and dozens of others are also described. Clinical presentation is dependent upon the organ(s) involved and those associated with unexpected death are expected to involve the cardiovascular system.

Sudden Cardiac Death in a Young Man with Migraine-associated Arrhythmia.

A 31-year-old man with migraine-induced syncope and bradycardia with subsequent pacemaker implantation died unexpectedly. Clinically unsuspected cardiac anomalies were found at autopsy including myocardial bridging of the left anterior descending artery and shelf-like coronary artery ostia. Nortriptyline was identified by toxicologic analysis.

A case example of asphyxia due to occupational exposure to airborne chemicals and review of workplace fatalities.

Although worker injury and fatalities have decreased since adoption of the Occupational Safety and Health Act in 1970, it remains an important safety issue. This article describes a 27-year-old white male who died from occupational exposure to airborne chemicals. Several trends in the last several decades, both in the types of injuries and the occupations associated with fatalities, are noted.

The importance of microscopic examination of the lungs in decedents with sustained central intravascular catheters: a nine-case series.

Indwelling intravascular catheters provide convenient access to healthcare personnel and also recreational intravenous drug users who inject suspensions of oral medications. A nine-case series of autopsies of clinically stable decedents with indwelling catheters and sudden death is herein presented. Pulmonary histologic findings were consistent with intravenous administration of oral medications in all cases.