A recent study suggests the first pediatric reference intervals (RIs) for a comprehensive trace element panel using both triple quadrupole inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) and high-resolution sector field ICPMS (HR-SF-ICPMS) technology. (J Appl Lab Med 2023; doi: 10.1093/jalm/jfad019).
Elemental deficiency and toxicity can have serious implications, especially in pediatrics. Trace element monitoring in children is an important part of renal, metabolic, and gastrointestinal disease management, but few studies have completed reference value profiling of trace elements in healthy children and adolescents with up-to-date analytical technology.
The researchers reported comprehensive reference values for 13 plasma and 22 whole trace elements from the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER). Study findings suggested that some trace elements require age-specific interpretation for appropriate clinical decision making. ICP-MS/MS and HR-SF-ICPMS were concordant for most assays. This supports the feasibility of common trace element RIs in pediatrics.
The researchers measured trace elements in whole blood and plasma samples using ICP-MS/MS in 172 subjects and HR-SF-ICPMS in 161 subjects. They established RIs and normal exposure limits according to Clinical and Laboratory Standards Institute guidelines.
None of the elements required sex partitioning, although 8 required age partitioning. Reference value distributions determined via ICP-MS/MS and HR-SF-ICPMS demonstrated excellent concordance with few exceptions. They included molybdenum, cobalt, and nickel.
In a discussion of three of the most ordered nutritional elements (copper, zinc, and selenium), the researchers noted that results from both methods had overlapping RIs and 90% confidence intervals. Additionally, the total difference between the upper and lower limits are within 15% for all three elements.
These results suggest that both instruments displayed similar analytical performance in terms of interference removal and results generation.
These findings support the feasibility of common trace element reference intervals in pediatrics, the researchers concluded.
SIMPLE TEST MAY DETERMINE OVARIAN OR BREAST CANCER RISK
Recent proof-of-concept research details a potential inexpensive first-line screening method for BRCA1 and BRCA2 mutations in healthy women at high genetic risk for ovarian or breast cancer (Nat Comm 2023; doi: 10.1038/s41467-023-38925-4).
With an eye toward early detection of cancer, improving prevention efforts, and focusing genetic counseling and testing among high-risk women, the researchers sought to determine whether circulating microRNAs (miRNAs) might vary by BRCA1/2 mutational status and whether circulating miRNAs profiles could be used to identify germline BRCA1/2 mutations among otherwise healthy women.
To derive a serum miRNA-based diagnostic test, the researchers used samples from 653 healthy women from six international cohorts. Of these, 53.6% of samples were from women with BRCA1/2 mutations and 46.4% were from women with wild type BRCA1/2. All individuals were cancer-free before and at least 12 months after sampling.
RNA sequencing followed by differential expression analysis identified 19 miRNAs significantly associated with BRCA mutations, 10 of which were ultimately used for classification: hsa-miR-20b-5p, hsa-miR-19b-3p, hsalet-7b-5p, hsa-miR-320b, hsa-miR-139-3p, hsa-miR-30d-5p, hsa-miR-17-5p, hsamiR-182-5p, hsa-miR-421, and hsa-miR-375-3p. The final logistic regression model achieved area under the receiver of operating characteristic curve 0.89 (95% CI: 0.87–0.93), 93.88% sensitivity and 80.72% specificity, in an independent validation cohort.
Mutated genes, menopausal status, or having preemptive oophorectomy did not affect classification performance.
The researchers concluded that laboratories may use circulating microRNAs to identify BRCA1/2 mutations in patients at high risk of cancer. This method may offer an opportunity to reduce screening costs, they added.
PREDIABETES MAY INCREASE FRACTURE RISK FOR MIDDLE AGED WOMEN
Recent research suggests that prediabetes in mid-life women may be a risk factor for future fractures (JAMA Netw Open 2023; doi: 10.1001/jamanetworkopen.2023.14835).
Diabetic bone disease and fractures are increasingly recognized as end-organ complications of diabetes. However, whether prediabetes is also a risk factor for fractures is uncertain.
In response to this question, researchers conducted a multicenter, longitudinal study of 1,690 women of median age 49.7 and various races and ethnicities from the Study of Women’s Health Across the Nation cohort. The women were premenopausal or early in perimenopause at the study’s start and transitioned to menopause during the study. They did not have type 2 diabetes or take bone-beneficial medication before menopause.
Mean follow-up time was 12 years. During that period, women had a baseline visit and 16 follow-up visits involving fasting blood glucose tests. Type 2 diabetes was defined as a fasting blood glucose level of 126 mg/dL or more, or taking certain drugs: metformin, sulfonylurea, meglitinide, thiazolidinedione, dipeptidyl peptidase 4 inhibitors, glucagonlike peptide-1 receptor agonists, or insulin. Prediabetes was defined as a fasting glucose of 100–125 mg/dL.
Outcome measures were time to first fracture after start of the menopause transition (MT), with censoring at first diagnosis of type 2 diabetes, initiation of bone-beneficial medication, or last follow-up. The researchers used Cox proportional hazards regression to examine the association (before and after adjustment for bone mineral density) of prediabetes before the MT with fracture during the MT and after menopause.
Compared to not having prediabetes at any visit before the menopause transition, having prediabetes at every visit prior to the transition was associated with a 120% greater hazard for fracture during the transition to menopause and after. This association was independent of bone mineral density at the start of the menopause transition.