Dina N. Greene

For cervical cancer screening, testing for high-risk human papillomavirus (hrHPV) detects more high-grade precancerous lesions, has a higher negative predictive value, and requires fewer lifetime screenings compared to cytology. As a result, both the US Preventive Services Task Force and the World Health Organization have endorsed hrHPV testing as the preferred screening method. Despite the utility, there are significant implementation challenges to adopting hrHPV primary screening across patients, providers, and institutions that must be addressed to ensure its widespread effectiveness. Here, we take a laboratory-centric approach to reviewing hrHPV primary screening, including discussion of specimen types and collection methods. For user experience, clinical and analytical validations, we focused on self-collected vaginal swab specimens stored dry during transport. Our analysis indicates that clinical laboratories should do their part to engage with institutional and clinical leadership to validate and promote the use of vaginal self-sampling for cervical cancer screening options within and outside the clinic. This work highlights the multiple studies that have validated dry swab collection as a simplified and high-quality method for hrHPV detection.

Introduction: Currently, there are few tools for monitoring recovery in substance use disorder. As substance use has increased in prevalence, tools for measuring recovery are needed to improve therapeutic outcomes. Measuring the kynurenine pathway for imbalances in metabolites could be a possible solution to monitor recovery. Methods: We developed a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method to quantify tryptophan, kynurenine, kynurenic acid, and quinolinic acid in urine. Metabolites were separated using a stepwise gradient and detected with an Agilent 6460 triple quadrupole mass analyzer. The samples were extracted using a simple protein precipitation protocol. Method validation was performed using routine toxicology urine samples and laboratory contrived samples. The performance characteristics assessed included precision, linearity, stability, interference, and matrix effects. Additionally, urine samples from two cohorts (illicit drug-negative and drug-positive; n = 120 per cohort) were analyzed for significant concentration differences in the four metabolites using Mann–Whitney, PCA, and Area Under the Receiver Operating Characteristic Curve statistical analysis. Results: The LC-MS/MS assay was linear from 195 to 100,000 ng/mL for tryptophan, 6 to 3000 ng/mL for kynurenine, 14 to 7200 ng/mL for kynurenic acid, and 125 to 64,000 ng/mL for quinolinic acid using an 8-point calibration curve. Imprecision ranged from 1.17% to 12.46% CV using two controls that spanned the analytical measurement range. Matrix effects were observed; however, the use of labeled internal standards matching the metabolites of interest minimized the impact on quantification. The extraction recovery efficiency was acceptable for the analytical validation. Ambient stability extended to 10 days, resulting in individual sample biases of up to 22%. A statistically significant increase in TRP, KYN, and QA was observed in drug-positive urine compared to illicit drug-negative urine (p < 0.01). Conclusion: We developed a rapid and sensitive LC-MS/MS method for quantifying tryptophan, kynurenine, kynurenic acid, and quinolinic acid in urine that can aid in future research elucidating the relationship between substance use disorders and tryptophan metabolism.

Background: There have been conflicting messages about the influence of female sex hormones on women's health, with historical messaging indicating that use of estrogen and/or progesterone in peri- or postmenopause poses a significant clinical risk to cisgender women. More recent guidance indicates that the benefit of hormone therapy (HT) outweighs the risks for symptomatic women. Exogenous estrogen use is also indicated for contraception and gender-affirming care. Despite the potential for broad applications, robust reference intervals for estradiol, progesterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are lacking, and guidelines indicate that measurement of 17-β-estradiol (E2), progesterone, LH, or FSH does not facilitate care in women who may be experiencing menopausal symptoms or women taking exogenous HT. Content: Here we review the physiological roles of estrogen, progesterone, LH, and FSH. We examine the modes of administration for estrogen and progesterone, clarify the nomenclature related to exogenous hormone use, and comprehensively review the literature for studies evaluating normal concentrations of these female gonadal axis hormones during the menstrual cycle. The content primarily focuses on cisgender women, but some aspects of these hormones in transgender women will also be discussed. Summary: Currently, E2, LH, FSH, and progesterone reference intervals for women remain incomplete. Although there are a variety of clinical indications that benefit women using HT, symptoms and shared decision-making should guide care. Collaborative efforts between clinicians and laboratory professionals to better define therapeutic or reference intervals for these hormones can advance women's health globally.

We read with interest the article by Messerlian et al., which endorsed continued use of race-specific alpha-fetoprotein (AFP) medians for open neural tube defect (ONTD) risk estimation ( 1). The authors retrospectively analyzed ONTD risk stratification results and demonstrated, using a cutoff of 2.5 AFP multiples of the median (MoMs), that adjusting AFP MoMs for race resulted in similar screen-positive rates (SPR) between Black (1.00%) and White (0.74%; P = 0.1) patients. Using race-agnostic AFP MoMs and weight adjustment factors led to a statistically significant difference of 0.86% in the SPR between Black and White patients, which corresponded to 17 (0.49%) additional positive screens in Black patients and 11 (0.11%) fewer positive screens in White patients. The authors assert that an increased SPR can burden Black patients with additional follow-up, anxiety, and possibly costly and invasive diagnostic testing, and that achieving equivalent SPRs using race-specific medians and weight adjustments provides the most racially equitable outcome.

Background: The integration of ChatGPT, a large language model (LLM) developed by OpenAI, into healthcare has sparked significant interest due to its potential to enhance patient care and medical education. With the increasing trend of patients accessing laboratory results online, there is a pressing need to evaluate the effectiveness of ChatGPT in providing accurate laboratory medicine information. Our study evaluates ChatGPT's effectiveness in addressing patient questions in this area, comparing its performance with that of medical professionals on social media. Methods: This study sourced patient questions and medical professional responses from Reddit and Quora, comparing them with responses generated by ChatGPT versions 3.5 and 4.0. Experienced laboratory medicine professionals evaluated the responses for quality and preference. Evaluation results were further analyzed using R software. Results: The study analyzed 49 questions, with evaluators reviewing responses from both medical professionals and ChatGPT. ChatGPT's responses were preferred by 75.9% of evaluators and generally received higher ratings for quality. They were noted for their comprehensive and accurate information, whereas responses from medical professionals were valued for their conciseness. The interrater agreement was fair, indicating some subjectivity but a consistent preference for ChatGPT's detailed responses. Conclusions: ChatGPT demonstrates potential as an effective tool for addressing queries in laboratory medicine, often surpassing medical professionals in response quality. These results support the need for further research to confirm ChatGPT's utility and explore its integration into healthcare settings.

Home sample collection for sexually transmitted infection (STI) screening options can improve access to sexual healthcare across communities. For Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), genital infections have classically been the focus for remote collection options. However, infections may go undiagnosed if sampling is limited to urogenital sites because some individuals only participate in oral and/or anal intercourse. Here we evaluated samples for CT/NG detection after several pre-analytical collection challenges. A paired provider to self-collection validation was performed on rectal [ n = 162; 22 + for CT and 9 + for NG by provider-collected (PC)] and throat ( N = 158; 2 + for CT and 11 + for NG by provider-collected) swabs. The positive percent agreement for CT and NG ranged from 90.9% to 100%. The discrepancies were more often positive on self-collected (SC) ( n = 9 SC+/PC−; n = 1 PC+/SC−; n = 1 PC+/SC Equiv.; n = 2 PC−/SC Equiv.). An empirical limit of detection (LoD) lower than the manufacturer’s claim (0.031 vs 2.5 IFU/mL for CT and 0.063 vs 124.8 CFU/ml for NG, respectively) was used to challenge additional variables. Common hand contaminants, including soap, hand sanitizer, lotion, and sunscreen were added to known positive (3× empirical LoD) or negative samples and did not influence detection. Samples at 2× and 10× the empirical LoD were challenged with extreme temperature cycling and extended room temperature storage. Detection was not affected by these conditions. These results indicate that remote self-collection is an appropriate method of sample acquisition for detecting extragenital CT/NG infections. Additionally, they provide a foundation towards meeting the regulatory standards for commercial testing of home collected extragenital samples. IMPORTANCE: There is a clinical need for expanded extragenital bacterial sexually transmitted infection (STI) testing options, but the current regulatory landscape limits the wide-spread promotion and adoption of such services. Improved access, particularly for the LGBTQ+ community, can be achieved by validating testing for specimens that are self-collected at a remote location and arrive at the laboratory via a postal carrier or other intermediary route. Here we provide valuable data showing that self-collected samples for anal and oropharyngeal STI testing are equally or increasingly sensitive compared with those collected by a provider. We systematically consider the effects of storage time, exposure to temperature extremes, and the addition of common toiletries on results.