Improving Time-to-Treatment for Advanced Non-Small Cell Lung Cancer Patients through Faster Single Gene EGFR Testing Using the Idylla™ EGFR Testing Platform.

Introduction: Patients with advanced-stage non-small cell lung cancer (NSCLC) may benefit from a short time-to-treatment (TTT). Predictive biomarker testing is performed prior to treatment, as recommended by various international expert consensus bodies. Genetic testing is more time-intensive than immunohistochemistry (IHC) and commonly contributes to prolonged TTT.

Detailed neuropathologic report of COVID-19 complicated by large intracerebral hemorrhage and periventricular lesions with macrophagic infiltrates.

Infection with the SARS-CoV-2 virus affects a wide range of systems. Significant involvement of the central nervous system has been described, including ischemic and hemorrhagic strokes. Thus far, neuropathologic reports of patients who passed away from COVID-19 have generally described non-specific findings, such as variable reactive gliosis and meningeal chronic inflammatory infiltrates, as well as the consequences of the infection's systemic complications on the brain, including ischemic infarcts and hypoxic/ischemic encephalopathy.

EGFR circulating tumour DNA testing: identification of predictors of ctDNA detection and implications for survival outcomes.

Background: EGFR T790M testing is the standard of care for activating EGFR mutation (EGFRm) non-small cell lung cancer (NSCLC) progressing on 1st/2nd generation TKIs to select patients for osimertinib. Despite sensitive assays, detection of circulating tumour deoxyribonucleic acid (ctDNA) is variable and influenced by clinical factors. The number and location of sites of progressive disease at time of testing were reviewed to explore the effect on EGFR ctDNA detection.

No Differences in Outcomes Between JAK2 V617F-Positive Patients with Variant Allele Fraction < 2% Versus 2-10%: A 6-Year Province-wide Retrospective Analysis.

Introduction: JAK2 V617F mutation is one of the major criteria in the diagnosis of myeloproliferative neoplasms (MPN) and its variant allele fraction (VAF) determines the disease phenotype and outcomes. This study aimed to define characteristics and outcomes of patients with JAK2 V617F VAF < 2% compared to patients with VAF 2%-10%.

Patients And Methods: We included 5079 patients with JAK2 V617F tested during 2010-2015 and identified 216 patients (4.

An actionable test using loss of heterozygosity in identifying high-risk oral premalignant lesions.

Objectives: To develop an actionable test using fluorescence capillary electrophoresis (FCE) to assess loss of heterozygosity (LOH) of histologically similar low-grade lesions (LGLs) to identify high-risk lesions for oral cancer progression.

Study Design: To determine the cutoffs of LOH, the FCE results of 52 surgical margin samples were used to compare with the existing LOH results from the previously validated P-GE approach. Using the developed FCE workflow, an independent set of 102 LGLs with known progression status was used to determine the LOH molecular risk (MR) patterns and associated risk of progression.

Initial Diagnosis of ALK-Positive Non-Small-Cell Lung Cancer Based on Analysis of ALK Status Utilizing Droplet Digital PCR.

We describe a novel droplet digital PCR (ddPCR) assay capable of detecting genomic alterations associated with inversion translocations. It is applied here to detection of rearrangements in the anaplastic lymphoma kinase (ALK) gene associated with ALK-positive non-small-cell lung cancer (NSCLC). NSCLC patients may carry a nonreciprocal translocation on human chromosome 2, in which synchronized double stranded breaks (DSB) within the echinoderm microtubule-associated protein-like 4 (EML4) gene and ALK lead to an inversion of genetic material that forms the non-natural gene fusion EML4-ALK encoding a constitutively active tyrosine kinase that is associated with 3 to 7% of all NSCLCs.

Quantitative Detection and Resolution of BRAF V600 Status in Colorectal Cancer Using Droplet Digital PCR and a Novel Wild-Type Negative Assay.

A need exists for robust and cost-effective assays to detect a single or small set of actionable point mutations, or a complete set of clinically informative mutant alleles. Knowledge of these mutations can be used to alert the clinician to a rare mutation that might necessitate more aggressive clinical monitoring or a personalized course of treatment. An example is BRAF, a (proto)oncogene susceptible to either common or rare mutations in codon V600 and adjacent codons.

Initial diagnosis of chronic myelogenous leukemia based on quantification of M-BCR status using droplet digital PCR.

Formed from a reciprocal translocation t(9:22)(q34;q11) of genetic material between the long arms of human chromosomes 9 and 22, the constitutively active breakpoint cluster region (BCR) Abelson 1 (ABL) tyrosine kinase BCR-ABL is known to be causative of chronic myelogenous leukemia (CML). In 98% of CML patients harboring the t(9:22)(q34;q11) translocation, known as the Philadelphia chromosome, the chimeric BCR-ABL oncogene is created through cleavage of the BCR gene within its major breakpoint region (M-BCR) and breakage of the ABL gene within a 100-kbp region downstream of exon 2a. Clinical detection of the fused BCR-ABL oncogene currently relies on direct visualization by fluorescence in situ hybridization (FISH), a relatively tedious assay that typically offers a detection limit of ca.

Sleep interruption associated with house staff work schedules alters circadian gene expression.

Background: Epidemiological studies indicate that disruption of circadian rhythm by shift work increases the risk of breast and prostate cancer. Our studies demonstrated that carcinogens disrupt the circadian expression of circadian genes (CGs) and circadian-controlled genes (CCGs) during the early stages of rat mammary carcinogenesis. A chemopreventive regimen of methylselenocysteine (MSC) restored the circadian expression of CGs and CCGs, including PERIOD 2 (PER2) and estrogen receptor β (ERS2), to normal.

A controlled trial of acute effects of human exposure to traffic particles on pulmonary oxidative stress and heart rate variability.

Background: For many individuals, daily commuting activities on roadways account for a substantial proportion of total exposure, as well as peak-level exposures, to traffic-related air pollutants (TRAPS) including ultrafine particles, but the health impacts of these exposures are not well-understood. We sought to determine if exposure to TRAPs particles during commuting causes acute oxidative stress in the respiratory tract or changes in heart rate variability (HRV), a measure of autonomic activity.

Methods: We conducted a randomized, cross-over trial in which twenty-one young adults took two 1.

Controlled exposure to diesel exhaust causes increased nitrite in exhaled breath condensate among subjects with asthma.

Objective: To determine whether oxidative/nitrosative stress plays a role in the acute effects of diesel exhaust (DE) on subjects with asthma.

Methods: In this crossover study, 16 subjects with mild to moderate asthma were exposed to clean filtered air or diluted DE (300 μg/m as PM2.5) for 1 hour with intermittent exercise.

Unique features of obstructive sleep apnea in World Trade Center responders with aerodigestive disorders.

Objectives: To compare obstructive sleep apnea (OSA) in World Trade Center (WTC) responders with aerodigestive disorders and snoring with non-WTC habitual snorers, and to distinguish features of OSA in a subset of responders with worsening of snoring after 9/11 from responders with previous habitual snoring.

Methods: Cross-sectional comparative study of 50 WTC Medical Monitoring and Treatment Program responders with aerodigestive disorders and snoring and 50 nonresponders with snoring. Responders with worsening of snoring after 9/11 were compared with previous habitual snorers.

Sickness response symptoms among healthy volunteers after controlled exposures to diesel exhaust and psychological stress.

Background: Interactions between acute exposures to environmental chemical contaminants and psychological stress may be important in situations where they are likely to co-occur, ranging in intensity from daily urban living to participation in war. Modification of symptomatic responses by stress may play a role in medically unexplained symptoms attributed to low-level chemical exposures.

Objectives: We hypothesized that the combination of exposure to diesel exhaust (DE) and acute psychological stress would cause sickness responses in healthy volunteers.

Quantification of 1-aminopyrene in human urine after a controlled exposure to diesel exhaust.

Diesel exhaust (DE) is a significant source of air pollution that has been linked to respiratory and cardiovascular morbidity and mortality. Many components in DE, such as polycyclic aromatic hydrocarbons, are present in the environment from other sources. 1-Nitropyrene appears to be a more specific marker of DE exposure.

Sensory and cognitive effects of acute exposure to hydrogen sulfide.

Background: Some epidemiologic studies have reported compromised cognitive and sensory performance among individuals exposed to low concentrations of hydrogen sulfide (H2S).

Objectives: We hypothesized a dose-response increase in symptom severity and reduction in sensory and cognitive performance in response to controlled H2S exposures.

Methods: In separate exposure sessions administered in random order over three consecutive weeks, 74 healthy subjects [35 females, 39 males; mean age (+/- SD) = 24.

Negative affect and chemical intolerance as risk factors for building-related symptoms: a controlled exposure study.

Objective: To assess whether differences in negative affect (NA) and chemical intolerance (CI) affect responses to chemical mixtures and stress in a controlled experimental model.

Methods: Participants were 130 nonsmoking, healthy women, recruited from a university community. Participants completed the Positive and Negative Affect Scale and the Chemical Odor Intolerance Index.

Nasal effects of a mixture of volatile organic compounds and their ozone oxidation products.

Objective: Our objective was to determine if low levels of a mixture of volatile organic compounds (VOCs) and their ozone (O3) oxidation products, similar to what might be found in "sick buildings," cause nasal irritation and inflammation under controlled exposure conditions.

Methods: Healthy, nonsmoking women (n=130) completed 2-hour controlled exposures to VOCs, VOCs and O3, and a masked air "MA" control in random order at least 1 week apart. VOCs and O3 concentrations were approximately 25 mg/m and approximately 40 ppb, respectively.

Health effects of a mixture of indoor air volatile organics, their ozone oxidation products, and stress.

In our present study we tested the health effects among women of controlled exposures to volatile organic compounds (VOCs), with and without ozone (O3), and psychological stress. Each subject was exposed to the following three conditions at 1-week intervals (within-subject factor): VOCs (26 mg/m3), VOCs + O3 (26 mg/m3 + 40 ppb), and ambient air with a 1-min spike of VOCs (2.5 mg/m3).

Responses to controlled diesel vapor exposure among chemically sensitive Gulf War veterans.

Objective: A significant proportion of Gulf War veterans (GWVs) report chemical sensitivity, fatigue, and unexplained symptoms resulting in ongoing disability. GWVs frequently recall an association between diesel and petrochemical fume exposure and symptoms during service. The purpose of the present study among GWVs was to evaluate the immediate health effects of acute exposure to chemicals (diesel vapors with acetaldehyde) with and without stress.

Loss of heterozygosity for loci on chromosome arms 1p and 10q in oligodendroglial tumors: relationship to outcome and chemosensitivity.

Oligodendroglial tumors frequently have deletions ofchromosomal loci on 1p and 19q. Loss of heterozygosity (LOH) of chromosome 10 may be a negative prognostic factor. We reviewed 23 patients with oligodendroglial tumors, to evaluate the frequency of 1p and 10q LOH and correlate with clinical outcome.

Cognitive effects of chronic exposure to lead and solvents.

Background: Occupational exposure to lead and solvents has declined steadily over the past 20 years, however, construction workers continue to be exposed to these neurotoxicants. The purpose of this study was to investigate the cognitive effects of chronic occupational exposure to lead and solvents.

Method: Based on K-XRF of tibial bone lead and occupational history of solvent exposure, subjects were classified into four exposure groups: lead (N = 40), solvent (N = 39), lead/solvent (N = 45), and control (N = 33).

Anxiety sensitivity and depression in multiple chemical sensitivities and asthma.

Patients with sensitivities to multiple chemicals report symptoms of cognitive dysfunction, respiratory distress, and mood disturbance. Lifetime and current psychiatric disorders, personality traits associated with symptom reporting, and tests of cognitive function were compared between 30 subjects with Multiple Chemical Sensitivities (MCS), 19 asthmatics, and 31 healthy controls. Relative to asthmatics and controls, more MCS subjects met criteria for current depression and somatization disorder.

Effect of vehicle use and maintenance patterns of a self-described group of sensitive individuals and nonsensitive individuals to methyl tertiary-butyl ether in gasoline.

The objective of this study was to compare the driving habits and vehicle maintenance patterns of individuals who report symptoms when exposed to methyl tertiary-butyl ether (MTBE) and those who are asymptomatic when exposed to the oxygenate. Participants were healthy volunteers (CON) and self-reported MTBE-sensitive individuals (SRS) who participated in a controlled exposure study of MTBE in gasoline. A questionnaire was developed to gather information about each participant's automobile usage, engine maintenance habits and fueling and driving patterns.

Stressors, personality traits, and coping of Gulf War veterans with chronic fatigue.

Objectives: preliminary surveys of Persian Gulf veterans revealed a significant prevalence of self-reported symptoms consistent with chronic fatigue syndrome (CFS). The purpose of this study was to compare self-reported life stressors, combat, and chemical exposures, personality and coping between Gulf War veterans with CFS and healthy veterans.

Methods: following a complete physical, psychiatric, and neuropsychological evaluation, 45 healthy veterans, 35 veterans with CFS and co-morbid psychiatric disorder, and 23 veterans with CFS and no co-morbid psychiatric disorder completed questionnaires assessing war and non-war-related life stressors, self-reports of environmental exposure (e.