Harmonization initiatives in laboratory medicine have a long history. Nevertheless, despite substantial efforts by international federations, scientific societies, and expert working groups, their implementation and widespread adoption remain incomplete, with many initiatives still at a relatively early stage of development. More recently, several initiatives have sought to identify scientifically sound yet pragmatic approaches to the harmonization of measurement units. To contribute to this debate, we invited experts from different disciplines of laboratory medicine, as well as a clinician, to provide their perspectives on the challenges, opportunities, and priorities for achieving greater harmonization. This Forum offers a unique opportunity to assess the current state of the art across multiple areas of laboratory medicine, including clinical chemistry, immunoassays, hematology, coagulation, molecular diagnostics, and serology. The contributions presented herein aim not only to highlight discipline-specific challenges but also to identify common principles and practical strategies that may guide future harmonization efforts. Although this paper does not propose a definitive roadmap for the harmonization of measurement units, its ultimate goal is to stimulate informed discussion and present a comprehensive spectrum of perspectives to international federations, national societies, regulatory authorities, and scientific journals. By doing so, it aims to support the identification of the most effective strategies for achieving greater consistency, comparability, and harmonization of laboratory reporting units worldwide.

Background: Bone turnover markers (BTMs) are increasingly used to assess bone remodeling and to monitor osteoporosis treatment. However, reference intervals remain largely undefined for African populations, limiting their clinical utility in these settings. Methods: We established reference intervals for intact procollagen type I N-propeptide (iPINP) and C-terminal telopeptide of type I collagen (beta-CTX-I) in a rigorously selected cohort of healthy adult Black African blood donors from C & ocirc;te d'Ivoire. Participants were screened for factors affecting bone metabolism, including kidney function, vitamin D status, and infectious diseases. Serum samples were processed under standardized conditions and analyzed using the IDS iSYS platform. Reference intervals were determined according to the CLSI C28-A3 guideline using the bootstrap non-parametric method, complemented by a Box-Cox transformation to verify robustness. The Bone Balance Index (BBI), defined as the standardized difference between observed and expected beta-CTX-I based on IPINP, was also explored in women >45 years. Results: In men (n = 90), beta-CTX-I concentrations showed reference interval of 181-610 ng/L (90 % CI: 168-196 / 480-745), and in women <= 45 years (n = 86), 167-378 ng/L (90 % CI: 166-166 / 343-413). For iPINP, the corresponding reference intervals were 30-169 mu g/L (90 % CI: 19-41 / 151-187) in men and 28-142 mu g/L (90 % CI: 24-33 / 107-176) in women <= 45 years. Box-Cox-based intervals were comparable, confirming the robustness of the bootstrap results. Compared to published data in non-African populations, beta-CTX-I values were generally lower, while iPINP values, particularly in men, tended to be higher. Among 27 women > 45 years, BBI values ranged from -1.36 to +8.59, with a median of 0.13; 20 (74 %) showed BBI > 0, suggesting a predominance of resorption, while 2 (7 %) had BBI < -1. Conclusions: This study provides the first rigorously derived reference intervals for beta-CTX-I and iPINP in a sub-Saharan African population, enabling more accurate interpretation of BTMs in African clinical contexts. The BBI may further help characterize bone remodeling balance at the individual level, though its clinical significance warrants further study.

Introduction:Sickle cell disease (SCD) carries a high risk of chronic kidney disease, necessitating accurate glomerular filtration rate (GFR) monitoring. This study evaluated the performance of creatinine-based (eGFRcrea), cystatin C-based (eGFRcys), and combined (eGFRcrea+cys) equations against directly measured GFR (mGFR). Methods:Clinically stable Congolese adults with SCD were recruited in 13 medical centers from Kinshasa. GFR was measured using iohexol plasma clearance. We compared the bias, precision, and accuracy of Chronic Kidney Disease Epidemiology (CKD-EPI) and European Kidney Function Consortium (EKFC) equations. Results:Among 207 patients included (24 [20;31] years and 58% of women), mean mGFR was 129 ± 38 ml/min/1.73 m2 with 41% of patients hyperfiltrating (mGFR >135 ml/min/1.73 m2). Among eGFRcrea equations, CKD-EPI was superior in hyperfiltrating patients, while EKFC performed better in normofiltrating patients. However, all eGFRcrea equations were suboptimal with only around 80% of estimated GFR (eGFR) results within 30% of mGFR. eGFRcys equations showed severe underestimation and poor accuracy. eGFRcrea+cys equations offered no clear added value. Conclusion:All eGFR equations were suboptimal in this young SCD population, with cystatin C performing particularly poorly. Given the limitations of current biomarkers, measuring GFR by a reference method remains the recommended standard. However, given the cost and logistical challenges of mGFR in low-income settings, relying on creatinine-based EKFC equation for normofiltrating patients and on creatinine based Chronic Kidney Disease Epidemiology Equation (CKD-EPIcrea) for hyperfiltrants appears to be a more feasible and pragmatic approach.

BACKGROUND:Dyslipidemia is frequent during critical illness, but its post-ICU evolution remains poorly characterized. This study evaluated changes in total cholesterol and triglyceride levels three months (M3) after ICU discharge. METHOD:We retrospectively analyzed a prospective cohort of ICU survivors who attended the M3 post-ICU consultation, with available measurements of total cholesterol, triglycerides, and C-reactive protein (CRP) blood levels. M3 lipid levels were compared to those obtained during the first ICU week and, when available, within three months before ICU admission. Hypertriglyceridemia (HTG) and hypocholesterolemia were defined as triglycerides >210 mg/dL (non-fasting) and total cholesterol ≤120 mg/dL, respectively. RESULTS:Among 188 patients, HTG was present in 42 (22.3%) at M3, with median triglycerides of 250 [223-329] mg/dL. In 69% of these patients, HTG occurred de novo. HTG was unrelated to diabetes, BMI, or ICU exposures, and correlated weakly with CRP (rs = 0.15, p = 0.025). Hypocholesterolemia was observed in 23 (12.2%) patients, mostly under lipid-lowering therapy. No significant associations were found between lipid abnormalities and muscle strength or readmissions. In a subgroup of 49 patients with pre-admission blood measurements, total cholesterol was higher at M3 than during or before ICU (p < 0.0001), while triglycerides were higher at M3 than before ICU admission (p = 0.019). CONCLUSION:Three months after ICU discharge, lipid recovery in survivors appears incomplete. While total cholesterol levels tend to normalize, HTG emerges in approximately 20% of the patients as an underrecognized metabolic sequela of critical illness.

An interlaboratory comparison study was conducted among five laboratories for determining 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) in human serum using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. The Centers for Disease Control and Prevention (CDC), Imperial College Healthcare NHS Trust, University College Cork, University of Liège, and University of Washington analyzed 50 single-donor samples and two new Standard Reference Materials (SRMs®). The results from each laboratory were compared with target values assigned by the National Institute of Standards and Technology (NIST) using a reference measurement procedure (RMP) and evaluated using Ordinary Deming linear regression and Bland-Altman analysis. Three of the five laboratory methods provided results that were in good agreement with the NIST RMP results showing linear regression slopes ranging from 0.972 to 1.003 and Bland-Altman mean bias of −0.092 nmol/L, 0.025 nmol/L, and 0.035 nmol/L. Two laboratories demonstrated a significant positive bias with linear regression slopes of 1.158 and 1.214 and Bland-Altman mean bias of 0.162 nmol/L and 0.708 nmol/L. The CDC method is currently used to assign “information only” values for 24,25(OH)2D3 in the quarterly distributions of the Vitamin D External Quality Assessment Scheme (DEQAS). Given the agreement (linear regression slope = 0.984, R2 = 0.996 and mean bias of −0.092 nmol/L) between the CDC method and the NIST RMP observed in this study, the CDC-assigned 24,25(OH)2D3 values in DEQAS may provide a more accurate reference than the current participant consensus mean values.

Context:Primary hyperparathyroidism (PHPT) is a common endocrine disorder for which minimally invasive parathyroidectomy (MIP) is the standard surgical approach. Intraoperative parathyroid hormone (IOPTH) monitoring is commonly performed using second-generation (2G) parathyroid hormone (PTH) assay. Objective:To compare the performance of IOPTH central sampling peripheral sampling, and third-generation (3G) vs 2G assays in patients with PHPT. Methods:This is a prospective cohort study conducted at American University of Beirut Medical Center, a tertiary hospital in Beirut, Lebanon. The study included 68 subjects with confirmed PHPT who achieved surgical cure, defined as normocalcemia at ≥6 months. IOPTH levels were measured from central and peripheral venous samples using 2G and 3G assays at various time points. Results:The median age was 57 years, and 80% were female. One-fourth had osteoporosis or reported kidney stones. Median preoperative calcium was 10.8 mg/dL with PTH 104 pg/mL, and 82% had single-gland disease. IOPTH levels were significantly higher with 2G assay and central sampling vs 3G assay and peripheral sampling. The proportion of patients meeting the Miami criterion did not differ between assays or sampling sites. Median percentage drop in IOPTH was greater with the 3G assay compared to 2G, across all time points, at both sampling sites. Conclusion:Although both assays similarly identified a ≥50% intraoperative decline, 3G assays demonstrated a steeper and more consistent drop, suggesting that higher assay-specific thresholds may improve decision-making. Central and peripheral sampling showed comparable predictive performance, although central sampling may allow earlier detection of PTH decline.

BACKGROUND:Osteoporosis increases fracture risk in older adults and is associated with impaired health-related quality of life (HRQoL). Osteoporosis-specific HRQoL instruments are widely used, but their measurement performance in older populations has not been comprehensively synthesised. OBJECTIVE:To systematically identify and synthesise development and validation studies of osteoporosis-specific HRQoL instruments for older adults, and to appraise their measurement properties using COSMIN criteria and a modified GRADE approach to inform instrument selection for clinical trials, routine care, and research. DESIGN:Systematic review. SETTING:Community-dwelling; Long-term care facility; Primary care facility. SUBJECTS:Older persons aged 60 years or over. METHODS:We searched Medline (Ovid), Embase, PsycINFO (Ovid), and AMED (Ovid) from inception to August 2024. We extracted and appraised evidence for COSMIN-defined measurement properties: content validity, structural validity, internal consistency, cross-cultural validity or measurement invariance, reliability, measurement error, criterion validity, hypothesis testing for construct validity, and responsiveness. Methodological quality was assessed using the COSMIN Risk of Bias checklist, measurement properties were rated against COSMIN criteria for good measurement properties, and certainty of evidence was graded using a modified GRADE approach. RESULTS:Forty-three studies reported the development and/or validation of nine osteoporosis-specific HRQoL instruments; language and version adaptations resulted in 15 instrument variants. Content validity was the most prominent limitation: only OPTQoL and the English Mini-OQLQ demonstrated sufficient evidence for multiple content validity components, while most widely used instruments lacked adequate evidence on item relevance, comprehensiveness, or comprehensibility. Evidence for internal structure was limited, with structural validity sufficient for ECOS-16 and QoLOS-NVFX, insufficient for QUALEFFO-41, and indeterminate for most other instruments. Cross-cultural validity and measurement invariance were almost entirely unexamined. By contrast, reliability and hypothesis testing for construct validity were more consistently supported, often with moderate-to-high certainty. Measurement error, interpretability, and responsiveness were poorly reported across instruments. CONCLUSIONS:The evidence base supports purpose-driven selection of osteoporosis-specific HRQoL instruments rather than a single preferred instrument. Across included studies, ECOS-16 shows the most consistently supported measurement properties in older adults for longitudinal assessment, although important evidence gaps remain (notably measurement error and cross-cultural validity). When brevity is the primary feasibility constraint in routine care, the Mini-OQLQ may be considered; however, evidence for responsiveness is limited.

Refined profiling of conjugated estrogens and androgens during equine pregnancy using liquid chromatography-tandem mass spectrometry (LC-MS/MS) could provide accurate fetal-sex determination. Current methods for fetal-sex prediction remain limited by timing, accuracy, and operator expertise. This study investigated sex-specific differences in maternal conjugated steroid profiles to develop a reliable, non-invasive predictive method. Samples were collected from 141 mares of various breeds starting at sixteen weeks of pregnancy. The samples were pooled according to gestational stage, divided into 28-day blocks, and analysed using a validated LC-MS/MS method. Quantified analytes included estrone, estradiol, equilin sulfates, glucuronides, and dehydroepiandrosterone sulfate. Method validation encompassed linearity, trueness, precision, accuracy, uncertainty, quantification limits, recovery, matrix effects, carryover, sensitivity, and stability. The effects of fetal sex, breed, parity, and maternal age on steroid concentrations were investigated. Data were split into a Test group for model development and a Validation group for performance assessment. Fetal sex was the principal factor influencing conjugated estrogen and dehydroepiandrosterone profiles (p = 0.01-0.0001). Female pregnancies exhibited higher classical conjugated steroid concentrations at block 5, whereas male pregnancies showed delayed elevations persisting until term. Equilin derivatives were consistently lower in males. Estrone sulfate (E1S) showed reliable univariate performance for fetal-sex prediction (area under the curve (AUC) 0.710-0.865, blocks 5-10). Multivariate models using all conjugated steroids achieved superior accuracy (AUC 0.747-0.912, blocks 5-11), providing an alternative method to univariate model and ultrasonography. The validated LC-MS/MS method improves understanding of equine feto-placental endocrinology and offers a non-invasive tool for practical fetal sexing.

PURPOSE OF REVIEW:Accurate measurement of parathyroid hormone (PTH) remains essential for the diagnosis and management of disorders of mineral metabolism, particularly in parathyroid disorders including in chronic kidney disease-mineral and bone disorder. Persistent inter-assay variability limits the comparability of clinical results across platforms and impedes guideline harmonization. This review focuses on recent advances in methodology, highlighting recent developments that move the field toward harmonization or even standardization of PTH assays. RECENT FINDINGS:Recent landmark studies have applied liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a candidate reference measurement procedure, enabling direct quantification of intact 1-84PTH with improved specificity. Novel immunocapture LC-MS/MS workflows demonstrate enhanced analytical precision and reveal substantive biases among commercial immunoassays. Recent progress in feasibility of harmonizing calibration was shown in a multicenter study where immunoassays were calibrated against LC-MS/MS reference methods, yielding reduced inter-assay bias, facilitating shared reference intervals. High-accuracy isotope-dilution mass spectrometry has been deployed to characterize reference materials, supporting future standard formulation. SUMMARY:Emerging LC-MS/MS methods and harmonization strategies represent significant progress toward future standardization of assays for PTH. While technical complexity and cost still remain barriers, recent developments point towards improved analytical comparability and enhanced clinical interpretation.

Saliva remains underexplored in metabolomics compared with widely used biofluids such as blood and urine. However, its noninvasive, rapid, and cost-effective collection, together with its suitability for self-sampling, makes it attractive for clinical and personalized medicine. Moreover, saliva is expected to provide complementary metabolic information on other biofluids. In this context, this study aims to identify an optimal sample collection and preparation protocol for maximizing informative metabolomic data from salivary nuclear magnetic resonance (NMR) profiles. Four preparation protocols, selected and adapted from the literature, were systematically compared using the number of identified metabolites, their concentrations, and intraday repeatability as evaluation criteria. Among them, an in-house-adapted method combining centrifugation, freeze-drying, and ultrafiltration proved most effective. This approach provided the broadest metabolome coverage, with 42 metabolites quantified. This method was further assessed using analysis of variance to determine intra- and interday precision. Most metabolites demonstrated excellent repeatability (coefficients of variation below 10%), confirming the protocol reliability for quantitative metabolomics. Overall, the optimized approach yields high-quality spectra, wide metabolic coverage, and strong analytical precision, supporting reproducible salivary NMR metabolomics. Beyond its methodological contribution, this work highlights saliva as a promising biofluid for diagnostics, disease monitoring, and personalized medicine, provided that collection and preparation procedures are appropriately standardized.

OBJECTIVES:Bone status indices (BSIs) are increasingly used in metabolic bone disease, yet global laboratory practices remain poorly characterized. Building on recent IOF-IFCC nomenclature and ESCEO-IOF-IFCC recommendations, we conducted an international descriptive survey of BSI practices. METHODS:A cross-sectional web-based questionnaire was distributed to laboratory professionals through IFCC and IOF networks, email invitations, and professional networks. It covered assay availability, specimen type, analytical platforms, external quality assessment (EQA), reference intervals or clinical decision thresholds, reporting units, interpretation, and reimbursement. Data were analyzed descriptively after duplicate screening, consistency review, and unit standardization. RESULTS:We received 231 responses, including 225 with geographic information from 41 countries across six continents. Marked heterogeneity was observed in analytical platforms, specimen types, reporting units, reference intervals or decision thresholds, EQA participation, and reimbursement. Reference intervals varied considerably, even among laboratories using the same manufacturer and instrument. EQA participation was high for total alkaline phosphatase (ALP) and parathyroid hormone (PTH), but lower for β-isomerized C-terminal telopeptide of type I collagen (β-CTX-I) and procollagen type I N-propeptide (PINP). Adoption of β-CTX-I and PINP was incomplete, although higher among laboratories following osteoporosis patients. Access to bone-specific ALP and tartrate-resistant acid phosphatase 5b remained limited. PTH testing was poorly harmonized because second- and third-generation assays were used in parallel. Vitamin D decision thresholds varied widely, and misordering of 1,25(OH)2D instead of 25(OH)D was frequently perceived. CONCLUSIONS:Global BSI laboratory practice remains highly heterogeneous. Harmonized units, intervals or decision thresholds, interpretative practices, EQA participation, assay access, and clinician education are needed.

This systematic review and meta-analysis aims to identify the most frequently reported blood-based biomarkers (BBMs) in randomised controlled trials (RCTs) addressing sarcopenia management, and to perform a preliminary evaluation of the effects of sarcopenia-specific interventions on BBMs concentrations. Medline, Embase and CENTRAL databases were searched to retrieve RCTs published until March 2024 (PROSPERO: CRD42024603238) on older participants with sarcopenia. Eligible studies applied a consensus definition of sarcopenia and reported BBM values before and after intervention. Meta-analyses were performed for BBMs reported in a minimum of 2 RCTs using a random effects model with a standardised mean difference (SMD) and a 95% confidence interval. Among 58 RCTs on sarcopenia management, only 21 (36.2%) assessed BBMs and none involved pharmacological interventions. Altogether, 47 distinct BBMs were identified. The most frequently reported were C-reactive protein, interleukin 6, tumour necrosis factor α, Insulin-like Growth Factor 1 (IGF-1). Muscle-specific BBM, follistatin, growth differentiation factor 8 and 15 were assessed in only 2 RCTs. Among non-muscle-specific BBMs, IGF-1 was significantly impacted by the studied interventions (SMD = 0.46, CI = [0.04; 0.88]). However, this change was not significant when analyses were restricted to RCTs reporting significant improvement in key sarcopenia measures. Despite substantial heterogeneity, few BBMs assessed in sarcopenia RCTs were muscle-specific and limited biomarkers responded to interventions. There is an urgent need to adopt recommendations regarding muscle-specific BBMs to be assessed in sarcopenia RCTs. Developing a standardised Core Outcome Set for sarcopenia intervention studies would enhance the standardisation of sarcopenia RCTs and ultimately improve disease management.

Whether antiretroviral therapy (ART) is always completely suppressive, or HIV might continue to replicate at low levels despite ART in some people with HIV (PWH), is still debated. Here, we intensified the ART regimen by doubling dolutegravir (DTG) dosage and investigated the impact of this strategy on HIV blood and tissue reservoirs, immune activation, and inflammation. Twenty HIV-infected adults, who had received a triple ART consisting of 50 mg DTG/600 mg abacavir/300 mg lamivudine pre-intensification and had been suppressed on ART for at least 2 years, were enrolled in a phase 2 randomized clinical trial (https://clinicaltrials.gov/ identifier: NCT05351684). Half of them received an additional 50 mg of DTG for a period of 84 days. As expected, plasma and tissue DTG concentrations significantly increased during the study period in the intensified group but not in the control group. Accordingly, significant decreases in total HIV DNA, intact HIV DNA, and cell-associated unspliced (US) HIV RNA in peripheral blood mononuclear cells, as well as in the US RNA/total DNA ratio, were observed in the intensified group but not in the control group. Intensification also modestly reduced markers of immune activation and exhaustion but had no measurable impact on systemic or tissue inflammation. Together with this, intensification resulted in a temporary decrease in the CD4/CD8 ratio that returned to baseline by day 84. Our results strongly suggest that the pre-intensification ART regimen was not completely suppressive. If confirmed in larger clinical trials, these results could have an impact on the clinical management of PWH and HIV curative strategies.

CONTEXT:Hypovitaminosis D during pregnancy is common and may have adverse maternal and neonatal effects. While randomized trials show that supplementation improves biochemical vitamin D status, the optimal dose and its effects on neonatal bone outcomes remain uncertain. OBJECTIVE:To compare the effects of 2 vitamin D supplementation doses during pregnancy on maternal and neonatal serum 25-hydroxyvitamin D (25(OH)D) at delivery, and on neonatal bone mineral content. METHODS:In this double-blind trial, pregnant women ≤17.5 weeks' gestation with baseline 25(OH)D 10 to 30 ng/mL were randomized to receive either 20 000 IU/week or 10 000 IU every 2 weeks (equivalent to 714 IU/day) vitamin D3. Primary outcomes were the proportion of women achieving a 25(OH)D level ≥20 ng/mL at delivery and neonatal bone mineral content (BMC) at ∼1 month of age. We used liquid chromatography tandem mass spectrometry (standard LC-MS/MS) at a CDC-certified laboratory. RESULTS:One hundred and ninety-two maternal neonatal pairs had complete biochemical data and 67 neonates had evaluable DXA scans. A significantly higher proportion (100%) of women and neonates (77%) in the higher dose group achieved 25(OH)D levels ≥20 ng/mL at delivery, compared with the lower dose group (85% and 40%, respectively, P = .001). Mean 25(OH)D in mothers and neonates at delivery followed a similar pattern (P = .001). However, neonatal subtotal whole-body BMC did not differ between groups (45.9 ± 8.5 vs 42.2 ± 7.1 g, respectively; P = .059), nor did neonatal bone mineral density or bone area. We did not identify any safety concerns related to supplementation. CONCLUSION:Higher dose vitamin D supplementation safely achieved biochemical sufficiency in mothers and neonates without measurable effect on neonatal bone outcomes.

Studies of humans provide evidence that dark chocolate is beneficial for cardiovascular health, particularly due to the antioxidant and vasorelaxant properties of polyphenols. The European Food Safety Authority (EFSA) delivered a health claim indicating that "cocoa flavan-3-ols help maintain the elasticity of blood vessels, contributing to normal blood flow". To obtain this claim, 200 mg of cocoa flavan-3-ols, equivalent to 10 g of dark chocolate, should be consumed daily. In addition to determining total antioxidant capacity (TAC) by four different methods, we examined if thirteen commercial dark chocolates of different origins (Ecuador, Panama, India, Guatemala, Mexico, Tanzania; % cocoa from 67 to 100%), handcrafted by a Belgian master chocolatier or produced on a large scale by a chocolate manufacturer both according to the more ethical bean-to-bar concept, may make this claim based on their flavan-3-ols content and ex vivo vasorelaxant activity. Among all chocolates tested, data showed that the two handcrafted Ecuadorian chocolates (70 and 100% cocoa) made with Arriba Nacional beans exhibited the highest TAC and total flavan-3-ols content, as well as the best ex vivo vasorelaxant effects. This contrasts with those produced by a chocolate manufacturer in Ecuador using the same beans. Nevertheless, their amount in total flavan-3-ols only reached, respectively 102.3 and 90.0 mg per 10 g raw material, thus none of the analyzed chocolates would meet the EFSA criteria for a cardiovascular health claim.