Nichole Korpi-Steiner

Osteoporosis in men

Osteoporosis in men causes significant morbidity and mortality. Bone health declines gradually, often insidiously; and in light of the advancing aging population poses a serious public health issue that is not well recognized. Studies of the past decade have expanded our understanding of the events within, as well as the regulation of, bone remodeling and provided better insight into the physiology and pathophysiology specific to the adult male skeleton. The clinical measurement of bone mineral density using dual-energy X-ray absorptiometry remains the gold standard for diagnosis of osteoporosis in males; and fracture risk assessment is now recognized as a preferred approach to guide treatment decisions. Utilizing surrogate end-points such as increasing bone mineral density and decreasing concentrations of bone resorption markers, clinical trials have demonstrated efficacy in pharmacological treatment of osteoporosis in the adult male. Unfortunately, few studies have evaluated the anti-fracture benefits in this population. Measurement of bone turnover markers may be an additional tool to monitor therapeutic responsiveness in addition to the measurement of bone mineral density.

Reducing analytical variation between point-of-care and laboratory HbA1c testing

Point‐of‐care (POC) HbA1c testing allows for timely treatment changes, improved glycemic control, and patient and provider satisfaction. Substantial variation between POC and laboratory HbA1c results has been reported. At our university hospital diabetes clinic, we observed significant negative bias in HbA1c with the DCA Vantage™ (Siemens Healthcare Diagnostics, Tarrytown, NY, USA) compared with the Tosoh G8 HPLC laboratory analyzer (Tosoh Bioscience, San Francisco, CA, USA). This led us to systematically analyze the bias with the goal of recalibrating the DCA to minimize bias.

Using a simulation model to assess risk of false negative point-of-care urinary human chorionic gonadotropin device results due to high-dose hook interference

BACKGROUND It is unclear if the point-of-care (POC) Clinitest hCG device is subject to high-dose hook interference from physiological concentrations of intact human chorionic gonadotropin (hCG), β-core fragment of hCG (hCGβcf), and hCG free β-subunit (hCGβ) found in urine during pregnancy. We used a simulation model to address this question and related our findings to our institutions pregnant population in order to assess risk for potential false-negative hCG results. METHODS The expected distribution of days relative to ovulation during routine POC hCG testing was estimated from 182 patients. Clinitest-Clinitek Status hCG device susceptibility to high-dose hook interference from hCG variants and potential risk of false-negative results as it relates to this population were evaluated by testing increasing concentrations of hCG, hCGβcf, hCGβ as well as urine simulating physiological hCG, hCGβcf and hCGβ concentrations expected during early pregnancy (≤44 days post-ovulation). RESULTS The Clinitest-Clinitek Status hCG device exhibited high-dose hook interference from hCGβcf alone, but not from hCG, hCGβ, or simulated physiological urinary concentrations of combined hCG, hCGβcf and hCGβ expected during early pregnancy. The majority of our patient population had urinary hCG testing conducted during early pregnancy. CONCLUSION The Clinitest-Clinitek Status hCG device is unlikely to exhibit false-negative urinary hCG results due to high-dose hook interference for women in early healthy pregnancy, although additional studies are necessary to determine potential risk in other patient populations. Visual interpretation of POC urinary hCG device results is an important failure mode to consider in risk analyses for erroneous urinary hCG device results.

Emerging Considerations for Noninvasive Prenatal Testing

Approaches to prenatal screening for common fetal chromosomal aneuploidies are undergoing a dynamic transformation in response to a greater understanding surrounding advances in the clinical utilities and limitations of noninvasive prenatal testing (NIPT).10 NIPT has been clinically adopted as a screening tool for aneuploidies, such as Down, Edwards, and Patau syndromes, and methodologies are primarily based on next generation sequencing of cell-free DNA (cfDNA) from maternal plasma. The cfDNA comprises maternal DNA fragments as well as placental DNA fragments that serve as a fetal surrogate marker. While NIPT was initially recommended as a screening option for high-risk women from about 10 weeks of gestation, recent clinical studies demonstrate that NIPT outperforms conventional screening approaches (e.g., first trimester combined test) regardless of the maternal age spectrum. The American College of Medical Genetics and Genomics updated recommendations in 2016 to include informing all pregnant women that NIPT is a screening option for conventionally screened aneuploidies. However, the potential expansion of NIPT utilization in prenatal care practices is faced with evolving challenges. Depending upon the laboratory, test methodology, and bioinformatics processes used, NIPT result reporting is not standardized. The decision of whether to use NIPT screening is ultimately that of the informed patient. However, it will also be driven by the ability to clearly communicate the risks and benefits of screening approaches by the clinical care team. This highlights the need for multidisciplinary collaboration in the clinical implementation of NIPT. To address these exciting advancements and emerging considerations, we invited a group of experts and early adopters of NIPT screening from multiple disciplines (genetic counseling, obstetrics, genomics, ethics, and clinical chemistry) to share their views on this topic. Does NIPT have a role beyond screening for fetal chromosomal aneuploidies in high-risk pregnancies? Judith Jackson: NIPT plays an important role in screening for …

Urinary fluticasone propionate-17beta-carboxylic acid to assess asthma therapy adherence

Although the National Asthma Education and Prevention Program Expert Panel Report 3 recommends referral to specialists to address adherence, guidelines do not provide a tool to determine nonadherence. This study was designed to prospectively evaluate the characteristics of urinary analysis of fluticasone propionate-17beta-carboxylic acid (FP17betaCA) as a test to verify if a specific patient has not taken fluticasone propionate (FP) within 16-24 hours. Urine of asthmatic subjects was prospectively analyzed 16-24 hours after witnessed administration of orally inhaled FP using liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis; limit of quantitation was 10.3 pg/mL. Results were compared with those from asthmatic subjects not receiving inhaled FP. Thirty asthmatic subjects receiving inhaled FP (2 oral inhalations of FP at 110 micrograms each or 1 oral inhalation twice daily of fluticasone and salmeterol in fixed combination at 250/50 micrograms for 1 week) were compared with 30 asthmatic subjects not receiving FP. FP17betaCA was detected in the urine of 30 of 30 asthmatic subjects receiving FP (median, interquartile range [IQR; 413.5, 212.8-1230.0] range 12.4-3290.0 pg/mL [corrected for urine creatinine: median, IQR {576.2, 188.1-1306.6} range 6.3-5425.9 ng/g Cr]) and was undetectable in 30 of 30 subjects not receiving inhaled FP. The sensitivity and specificity of LC-MS/MS to detect FP17betaCA in urine were 100% (95% exact binomial confidence interval, 88-100) and 100% (95% exact binomial confidence interval, 88-100), respectively. Analysis of FP17betaCA in urine provides a sensitive method that may be used to verify that a specific patient may not have administered FP within a 16- to 24-hour window before testing.

Suspected Testosterone-Producing Tumor in a Patient Taking Biotin Supplements

Abstract A perimenopausal woman presented with palpitations, hirsutism, and inability to lose weight. Laboratory tests revealed an unusual endocrine hormonal profile including pituitary hormones (TSH, ACTH, and prolactin) below reference intervals and gonadal (testosterone) and adrenal (cortisol) hormones above reference intervals. Ultimately, after a comprehensive workup including a scheduled surgical procedure, abnormal laboratories were determined due to biotin interference. Biotin (vitamin B7) is a water-soluble vitamin and essential cofactor for the metabolism of fatty acids, glucose, and amino acids. The recommended daily intake of biotin for adults is 30 µg/d. Many over-the-counter products, particularly those marketed for hair, skin, and nail growth, contain biotin 100-fold of recommended daily intake. This case is unique due to the abnormalities observed not only in the well-described TSH “sandwich” immunoassay, but also in tests for gonadal steroids, adrenal, and pituitary hormones. Falsely high as well as falsely low results can be ascribed to biotin. Competitive immunoassays (Fig. 1A)— in this case, tests used initially for serum cortisol and testosterone— can demonstrate falsely high results. Interference falsely lowers the immunometric “sandwich” immunoassay (Fig. 1B)—in this case, TSH. Biotin effect on our patient’s endocrine testing led to decidedly abnormal findings, unnecessary medical referrals and diagnostic studies, and comprehensible psychological distress. Interference with one immunoassay, TSH, persisted a full 2 weeks after discontinuation of biotin; indeed, some tests demonstrate sensitivity to lesser quantities of biotin. Improved communication between patients, health care providers, and laboratory professionals is required concerning the likelihood of biotin interference with immunoassays.

Advances in Cardiac Biomarkers of Acute Coronary Syndrome

Acute coronary syndrome (ACS) encompasses a pathophysiological spectrum of cardiovascular diseases, all of which have significant morbidity and mortality. ACS was once considered an acute condition; however, new treatment strategies and improvements in biomarker assays have led to ACS being an acute and chronic disease. Cardiac troponin is the preferred biomarker for the diagnosis of myocardial infarction, and there is considerable interest and efforts toward development and implementation of high-sensitivity cardiac troponin (hs-cTn) assays worldwide. Analytical and clinical performance characteristics of hs-cTn assays as well as testing limitations are important for laboratorians and clinicians to understand in order to utilize testing appropriately. Furthermore, expanding the clinical utility of hs-cTn into other cohorts such as asymptomatic community dwelling populations, heart failure, and chronic kidney disease populations supports novel opportunities for improved short- and long-term prognosis.