Jason Y. Park

Introduction: Detection of Measles virus (MeV) RNA is an important method for confirming infection. This study described the clinical validation of a qualitative real-time reverse transcriptase–polymerase chain reaction (RT-PCR) assay for MeV detection. Methods: A real-time RT-PCR assay was developed and validated using primers and probes previously reported in the literature. The assay was evaluated using reference materials, cultured virus, and previously tested clinical throat swab samples. An automated workflow was established for RNA extraction, RT-PCR amplification, and result reporting using robotic platforms and a real-time PCR instrument. The assay targets the measles nucleoprotein (N) and hemagglutinin (H) genes, with human RNase P gene used as an internal control. Results: The MeV RT-PCR assay has a limit of detection of 500 genome copies per milliliter. The assay was tested against 85 different samples: 50 positive clinical samples and reference materials and 35 negative clinical samples or reference materials. All expected results were correctly identified, giving 100% sensitivity (50/50) and specificity (35/35). The assay showed 100% interassay and intra-assay reproducibility. No cross-reactivity was observed with other respiratory viruses or common bacterial and fungal pathogens. Discussion: This automated measles RT-PCR assay demonstrated high accuracy, sensitivity, specificity, and reproducibility.

Background Years into the immune checkpoint inhibitor (ICI) era, immune-related adverse events (irAE) remain largely unpredictable. Prior studies have examined irAE associations with weight and metabolic diseases, yielding mixed findings. We therefore analyzed these and other variables potentially associated with heightened inflammation and irAE development. Methods For ICI-treated individuals enrolled in a prospective institutional clinical and biospecimen registry, we collected demographic, clinical, laboratory, and residence data, pre-ICI serum cytokine levels, and irAE details. We calculated metabolic syndrome (MetS) and area deprivation index (ADI, a measure of neighborhood socioeconomic status), both of which have been associated with heightened inflammation. Patients were categorized as having MetS if they had ≥ 3 of 5 criteria at ICI initiation: hypertension, obesity, elevated HbA1c, low HDL, elevated triglycerides. Baseline serum cytokine/chemokine levels were determined using a multiplex platform. We analyzed associations across variables using logistic regression, Mann–Whitney U, and Cochran Armitage tests, accounting for multiple comparisons. Results Overall, 178 ICI-treated patients were included in the analysis, of whom 99 (56%) were classified as having MetS. In multivariable analysis, patients with MetS had greater odds of both grade ≥ 2 irAE (OR 2.82; 95% CI, 1.35–6.14; P = 0.007) and grade ≥ 3 irAE (OR 3.53; 95% CI 1.27–11.68; P = 0.02). However, MetS was not associated with pre-treatment cytokine levels. In contrast, ADI was associated with multiple inflammatory cytokines but not with MetS or irAE. Conclusions MetS is associated with increased likelihood of moderate and severe irAE. The mechanism and mitigation of this risk merit further investigation.

Introduction: Racial and ethnic disparities in the presentation and outcomes of lung cancer are widely known. To evaluate potential factors contributing to these observations, we measured systemic immune parameters in Black and White patients with lung cancer. Methods: Patients scheduled to receive cancer immunotherapy were enrolled in a multi-institutional prospective biospecimen collection registry. Clinical and demographic information were obtained from electronic medical records. Pre-treatment peripheral blood samples were collected and analyzed for cytokines using a multiplex panel and for immune cell populations using mass cytometry. Differences between Black and White patients were determined and corrected for multiple comparisons. Results: A total of 187 patients with non-small cell lung cancer (Black, 19; White, 168) were included in the analysis. There were no significant differences in baseline characteristics between Black and White patients. Compared to White patients, Black patients had significantly lower levels of CCL23 and CCL27, and significantly higher levels of CCL8, CXCL1, CCL26, CCL25, CCL1, IL-1 b, CXCL16, and IFN-γ (all P P <0.05). Conclusions: Black and White patients with lung cancer exhibit several differences in immune parameters, with Black patients exhibiting greater levels of numerous pro-inflammatory cytokines and cell populations. The etiology and clinical significance of these differences warrant further evaluation.

Whole-body 18F-FDG PET/CT (WBP) has the potential to impact management of infective endocarditis (IE) through identification of areas of occult primary or metastatic infection. This study compares the characteristics and outcomes in groups of patients with IE who did and did not have WBP as part of their evaluation to help guide how this imaging may be optimally utilized. We performed a retrospective cohort study of hospitalized patients discussed at the multidisciplinary endocarditis meeting at a tertiary care center in Michigan, USA between June 2018 and January 2022. Protocolized chart review was performed by three study team members. Although a mortality benefit was not observed, WBP played an important role in the management of patients with IE with identification of areas of metastatic infection that required longer antimicrobial treatment or addition of suppressive antimicrobials. Further analyses are planned to understand which patients with IE may benefit most from WBP. All Authors: No reported disclosures

In 1955, Clinical Chemistry was established as a peer-reviewed scientific journal by the American Association of Clinical Chemists. In 1976, the association changed its name to reflect broadening membership to become the American Association for Clinical Chemistry. This year, which is the association’s 75th anniversary, the association again changed its name and is now the Association for Diagnostics & Laboratory Medicine. Beginning with the August 2023 issue, the journal’s cover reflects the transition from the American Association of Clinical Chemists to the Association for Diagnostics & Laboratory Medicine. While the association has changed its name, the journal still maintains its title Clinical Chemistry and its content continues to reflect a wide variety of laboratory medicine topics. In keeping with the times, the breadth of subject matter in the transitional August issue illustrates the changes in the association and journal that have occurred over the past 30 years. In that issue alone there are articles on diabetes, Helicobacter pylori, preimplantation genetic testing, population newborn screening by genomic approaches, and epidemiologic studies of N-terminal pro b-type natriuretic peptide. The most recent change in the name of the association and the diverse subjects covered in the journal represent the wide scope of the current and future practice of laboratory medicine.

Metabolic flux augmentation via glucose transport activation may be desirable in Glucose transporter 1 (Glut1) deficiency (G1D) and dementia, whereas suppression might prove useful in cancer. Using lung adenocarcinoma cells that predominantly express Glut1 relative to other glucose transporters, we screened 11,613 compounds for effects on the accumulation of an extracellularly-applied fluorescent glucose analog. 5 drugs currently prescribed for unrelated indications or preclinically-characterized robustly enhanced intracellular fluorescence. Additionally identified were 37 novel activating and 9 inhibitory compounds lacking previous biological characterization. Because few glucose-related mechanistic or pharmacological studies were available for these compounds, we developed a method to quantify G1D mouse behavior to infer potential therapeutic value. To this end, we designed a 5-track apparatus to record and evaluate spontaneous locomotion videos. We applied this to a G1D mouse model that replicates the ataxia and other manifestations cardinal to the human disorder. Because the first two drugs that we examined in this manner (baclofen and acetazolamide) exerted various impacts on several gait aspects, we used deep learning neural networks to more comprehensively assess drug effects. Using this method, 49 locomotor parameters differentiated G1D from control mice. Thus, we used parameter modifiability to quantify efficacy on gait. We tested this by measuring the effects of saline as control and glucose as G1D therapy. The results indicate that this in vivo approach can estimate preclinical suitability from the perspective of G1D locomotion. This justifies the use of this method to evaluate our drugs or other interventions and sort candidates for further investigation. Significance Statement One approach to Glucose transporter I (Glut1) deficiency syndrome (G1D), dementia and cancer treatment is modulation of glucose transport. Using lung adenocarcinoma cells rich in Glut1, we identified, in high-throughput fashion, activators and inhibitors of fluorescent glucose analog transport. We also developed a gait testing platform for the deep learning neural network analysis of G1D mice that quantifies drug impact on 49 gait parameters, thus evaluating the potential preclinical efficacy of these drugs and other interventions via analysis of locomotion.

For almost 70 years, Clinical Chemistry has been a leading journal that has communicated advances in the clinical laboratory and shaped the identity of laboratory professionals. As a journal of the American Association for Clinical Chemistry (AACC), Clinical Chemistry continues to serve the members of AACC and the larger healthcare community. This current issue is the first published under a new editorial board. The tenure of the former editor-in-chief, Nader Rifai, was marked by success in the publication of landmark original research and the expansion of educational content including innovations such as clinical case studies, podcasts, and journal clubs. A key opportunity for the new editorial board will be to maintain and build upon the achievements of Dr. Rifai and of previous editors.