Search

BACKGROUND Analytical characteristics of methods to measure biomarkers determine how well the methods measure what they claim to measure. Transparent reporting of analytical characteristics allows readers to assess the validity and generalizability of clinical studies in which biomarkers are used. Our aims were to assess the reporting of analytical characteristics of biomarkers used in clinical research and to evaluate the extent of reported characterization procedures for assay precision. METHODS We searched 5 medical journals (Annals of Internal Medicine, JAMA: The Journal of the American Medical Association, The Lancet, The New England Journal of Medicine, and PLOS Medicine) over a 10-year period for the term “biomarker” in the full-text field. We included studies in which biomarkers were used for inclusion/exclusion of study participants, for patient classification, or as a study outcome. We tabulated the frequencies of reporting of 11 key analytical characteristics (such as analytical accuracy of test results) in the included studies. RESULTS A total of 544 studies and 1299 biomarker uses met the inclusion criteria. No information on analytical characteristics was reported for 67% of the biomarkers. For 65 biomarkers (3%), ≥4 characteristics were reported (range, 4–8). The manufacturer of the measurement procedure could not be determined for 688 (53%) of the 1299 biomarkers. The extent of assessments of assay imprecision, when reported, did not meet expectations for clinical use of biomarkers. CONCLUSIONS Reporting of the analytical performance of biomarker measurements is variable and often absent from published clinical studies. We suggest that readers need fuller reporting of analytical characteristics to interpret study results, assess generalizability of conclusions, and compare results among clinical studies.

Background Low initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers dropping to undetectable levels within months after infection have raised concerns about long-term immunity. Both the antibody levels and the avidity of the antibody–antigen interaction should be examined to understand the quality of the antibody response. Methods A testing-on-a-probe “plus” panel (TOP-Plus) was developed to include a newly developed avidity assay built into the previously described SARS-CoV-2 TOP assays that measured total antibody (TAb), surrogate neutralizing antibody (SNAb), IgM, and IgG on a versatile biosensor platform. TAb and SNAb levels were compared with avidity in previously infected individuals at 1.3 and 6.2 months after infection in paired samples from 80 patients with coronavirus disease 2019 (COVID-19). Sera from individuals vaccinated for SARS-CoV-2 were also evaluated for antibody avidity. Results The newly designed avidity assay in this TOP panel correlated well with a reference Bio-Layer Interferometry avidity assay (r = 0.88). The imprecision of the TOP avidity assay was Conclusions This highly precise and versatile TOP-Plus panel with the ability to measure SARS-CoV-2 TAb, SNAb, IgG, and IgM antibody levels and avidity of individual sera on one sensor can become a valuable asset in monitoring not only patients infected with SARS-CoV-2 but also the status of individuals’ COVID-19 vaccination response.

A 31-year-old Chinese woman with bilateral upper extremity swelling presented to the emergency department at the 20th week of gestation. According to the patient, “normal fetal movement” had stopped 3 days before admission. No abdominal pain or obvious vaginal bleeding was noted. Her body temperature was 36.5 °C and blood pressure was 110/70 mmHg with a heart rate of 80 beats/min. However, there was no fetal heart rate or movement that could be detected by ultrasonography examination, suggesting spontaneous abortion. Although there was no significant family history, the patient had 1 stillbirth 3 years ago at 27 weeks of gestation, accompanied by eclampsia before her labor induction. Because her fetus showed no signs of life with ultrasonography examination, the patient agreed to have ethacridine (Rivanol)-induced labor on day 3 of her hospitalization. On the day of her induction, her blood pressure went up to 158/82 mmHg with proteinuria (urine chemistry: protein +4) and low platelet count (90 × 109/L, normal range 100–300 × 109/L), consistent with a diagnosis of preeclampsia. Magnesium sulfate was administrated during and after the delivery for seizure prophylaxis. After delivery, her blood pressure decreased to 133/81 mmHg and other preeclampsia symptoms resolved in the next few days before discharge. According to the patient's medical record, she had unremarkable endocrine status and negative screening results for infections [toxoplasmosis, rubella cytomegalovirus, herpes simplex, HIV, syphilis, HBV (hepatitis B virus), and HCV (hepatitis C virus)]. The patient had a triple test (α-fetoprotein, human chorionic gonadotropin, and estriol) in her second trimester that showed low risk for Down syndrome. The fetus was sent for autopsy and developmental anomalies were excluded. Relevant laboratory values are shown in Table 1. View this table: Table 1. APS testing and autoimmune antibody testing results. ### QUESTIONS TO CONSIDER 1. How is recurrent pregnancy loss (RPL)4 defined and what …

BACKGROUND The use of serum human chorionic gonadotropin (hCG) and progesterone to identify patients with ectopic pregnancy (EP) has been shown to have poor clinical utility. Pregnancy-associated circulating microRNAs (miRNAs) have been proposed as potential biomarkers for the diagnosis of pregnancy-associated complications. This proof-of-concept study examined the diagnostic accuracy of various miRNAs to detect EP in an emergency department (ED) setting. METHODS This study was a retrospective case–control analysis of 89 women who presented to the ED with vaginal bleeding and/or abdominal pain/cramping and received a diagnosis of viable intrauterine pregnancy (VIP), spontaneous abortion (SA), or EP. Serum hCG and progesterone concentrations were measured by immunoassays. The serum concentrations of miRNAs miR-323-3p, miR-517a, miR-519d, and miR-525-3p were measured with TaqMan real-time PCR. Statistical analysis was performed to determine the clinical utility of these biomarkers, both as single markers and as multimarker panels for EP. RESULTS Concentrations of serum hCG, progesterone, miR-517a, miR-519d, and miR-525-3p were significantly lower in EP and SA cases than in VIP cases (P < 0.01). In contrast, the concentration of miR-323-3p was significantly increased in EP cases, compared with SA and VIP cases (P < 0.01). As a single marker, miR-323-3p had the highest sensitivity of 37.0% (at a fixed specificity of 90%). In comparison, the combined panel of hCG, progesterone, and miR-323-3p yielded the highest sensitivity (77.8%, at a fixed specificity of 90%). A stepwise analysis that used hCG first, added progesterone, and then added miR-323-3p yielded a 96.3% sensitivity and a 72.6% specificity. CONCLUSIONS Pregnancy-associated miRNAs, especially miR-323-3p, added substantial diagnostic accuracy to a panel including hCG and progesterone for the diagnosis of EP.

A 40-year-old woman with a history of Takayasu arteritis, Sjogren syndrome, Raynaud phenomenon, and endometriosis status after hysterectomy with salpingo-oophorectomy presented for participation in a research protocol. Her serum human chorionic gonadotropin (hCG)2 concentration was 7 IU/L (reference interval ≤5 IU/L) (Table 1). The patient did not have a history of gestational trophoblastic disease (GTD) or malignancy. The physician asked how …

To the Editor: Current clinical practice guidelines recommend measuring serum cystatin C (CysC)1 and using the CKD-EPI 2012 CysC-based equations to report estimated glomerular filtration rate (eGFR) to evaluate chronic kidney disease in situations where eGFR based on serum creatinine is inaccurate. These conditions include individuals with early-stage kidney disease or low muscle mass, children, and the elderly (1). Despite the introduction of ERM-DA471/IFCC international reference materials in 2010, widespread use of CysC has been compromised by lack of agreement among commercial assays. A report of the College of American Pathologists (CAP) 2014 CYS survey showed substantial variability among results by participating laboratories using different methods (2). For example, with CysC target values of 0.96 and 2.37 mg/L, method-specific mean values varied by 29% and 36%, respectively (2). The BN II (Siemens) assay was used in the original study that developed and validated the CKD-EPI 2012 CysC-based equations (3). However, it is not widely appreciated (even by experts in the field) that the BN II CysC results in that study were not directly traceable to …