Reference Range Research Articles

The erythrocyte sedimentation rate and other markers of inflammation in cats tested for Leishmania infantum and feline immunodeficiency virus antibodies

BackgroundIn endemic areas, Leishmania infantum and feline immunodeficiency virus (FIV) co-infection occurs in cats, and may favour a progressive course of feline leishmaniosis. Abnormalities in serum protein fractions have been reported, but inflammation markers have scarcely been studied. Erythrocyte sediment rate (ESR) is a marker of inflammation that is poorly used in veterinary medicine, but it has been evaluated in EDTA blood using a recently introduced automatic device. We studied ESR and a pool of feline markers of inflammation (MoI) in cats L. infantum (Li+) and/or FIV antibody-positive (Li+FIV+/FIV+) with the aims (a) to evaluate ESR as MoI in cats with the infectious and clinical conditions considered and (b) to provide data about a pool of MoI never investigated in the feline infections studied and in other cat diseases before.MethodsThis prospective controlled study included 35 study group cats (Li+, n = 20; FIV +, n = 8; Li+FIV+, n = 7) and ten healthy antibody-negative control cats. Clinical findings at physical examination and selected clinical pathological abnormalities related to inflammation were statistically analysed in relation to the infectious status and ESR values.ResultsESR values were higher in Li+, FIV+, and Li+FIV+ cats compared with control cats, and 40% of the study group cats had ESR values above the reference interval (RI). ESR positively correlated with some positive MoI and negatively with some negative MoI studied. Additionally, a higher prevalence of ESR values above the RI has been detected in cats with hypoalbuminemia or hypergammaglobulinemia and higher ESR values were measured in cats with serum protein electrophoresis (SPE) fraction abnormalities. Correlations were also found with erythrocytes, hemoglobin, hematocrit and some erythrocyte indices. FIV+ and Li+FIV+ cats had a higher prevalence of increased ESR values, and almost all had SPE abnormalities and more severe clinical presentations compared with Li+ cats.ConclusionsAbnormal levels of MoI were found in almost all parameters studied, particularly in FIV+ and Li+FIV+ cats. Also, ESR can be used as a marker of inflammation in cats with L. infantum and/or FIV infection.Graphical

A Novel Tool for the Rapid and Transparent Verification of Reference Intervals in Clinical Laboratories.

Background/Objectives: We present a software package called reflimR (Version 1.0.6), which enables rapid and transparent verification of reference intervals from routine laboratory measurements. Our method makes it easy to compare the results with specified target values and facilitates the interpretation of deviations using traffic light colors. Methods: The algorithm includes three procedural steps: (a) definition of an appropriate distribution model, based on Bowley's quartile skewness, (b) iterative truncation, based on a modified boxplot method to obtain the central 95% of presumably inconspicuous results, and (c) extrapolation of reference limits from a truncated normal quantile-quantile plot. Results: All algorithms have been combined into one consolidated library, which can be called in the R environment with a single command reflim (x). Using an example dataset included in the package, we demonstrate that our method can be applied to mixed data containing a substantial proportion of pathological values. It leads to similar results as the direct guideline approach as well as the more sophisticated indirect refineR software package. As compared to the latter, reflimR works much faster and needs smaller datasets for robust estimates. For the interpretation of the results, we present an intuitive color scheme based on tolerance ranges (permissible uncertainty of laboratory results). We show that a relatively high number of published reference limits require careful reevaluation. Conclusions: The reflimR package closes the gap between direct guideline methods and the more sophisticated indirect refineR method. We recommend reflimR for the rapid routine verification of large amounts of reference limits and refineR for a careful analysis of unclear or doubtful results from this check.

Trace Elements in Hermann's Tortoises (Testudo hermanni) According to Sex, Season, and Sampling Region in Central Europe.

Some trace elements are essential for the health of vertebrates, but little is known about their function, the amounts required, and the factors influencing their metabolism in tortoises. The aim of this study was therefore to measure trace elements (chromium (Cr), cobalt (Co), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), molybdenum (Mo), selenium (Se), zinc (Zn)) in heparinized blood plasma of Hermann's tortoises (Testudo hermanni) (n = 520) from March to September 2022 using inductively coupled plasma mass spectrometry (ICP-MS) and to establish specific reference intervals. Additionally, the influence of sex, season, and region of sample collection on the measured values were evaluated. Significant (p ≤ 0.05) sex-specific differences were found for Cu, Mg, and Mn; seasonal differences were found for Cr, Cu, Mn, Mo, and Se; and the region in which the tortoises were kept significantly impacted Cr, Cu, Fe, Mg, Mo, and Se levels. The results show that all of these factors should be consider when establishing and interpreting blood trace element levels in tortoises.

Utility of anthropometry in defining overweight and obesity in urban South Indian children.

Waist-based indicators of obesity are being used to detect central obesity and are predictive for metabolic syndrome (MS). The aim of the study is to assess the basic anthropometric indices in children, to determine the prevalence of overweight and obesity, and to determine the association between various waist-based measurements and body mass index (BMI). A cross-sectional study was conducted among children aged 10 to 15 years attending government corporation schools in Chennai. Basic anthropometric measurements were taken. BMI, waist circumference/height ratio (WHtR), and waist circumference/hip circumference ratio (WHR) were calculated. The percentiles (Indian reference cutoffs) were determined for waist circumference (WC) and BMI. The prevalence of overweight and obesity was determined and compared to waist-based parameters. Of 820 children, males constituted 47.1%. Stunting was seen in 9.8% and 7.8% were underweight. 8.2% had BMI less than the 3rd percentile. The prevalence of overweight and obese children was 9% and 3.2%, respectively, with female predominance. The majority had WC less than the 5th percentile. The prevalence of children under risk for MS based on WC >70th percentile was 4.5% and based on WHtR >0.5 was 8.2%. A significant association was identified between all waist-based anthropometric measurements to detect children at risk for MS and overweight/obese children as per BMI category. WHtR >0.5 was an indicator of overweight/obese children in logistic regression analysis. Early identification of children at risk of MS would require a combination of BMI to detect general obesity and waist-based anthropometric measurements to identify central obesity.

Determination of the reference interval for urinary klotho to creatinine ratio of healthy dogs.

For several years, alpha klotho has been considered as a candidate biomarker in chronic kidney disease (CKD), progression of CKD and CKD mineral bone disorders (CKD-MBD). The evidence on the relationship between klotho and kidney function is controversial in some areas. The aim of the study was to identify the influence of age, sex and breed on urinary alpha klotho, values in the early stages of CKD within the studied population and determine a reference interval in a group of healthy dogs. Significantly higher values were measured in older dogs over 6 years old (p = 0.026, p = 0.0007) and in the breed German Shepherd than Belgian Shepherd (p = 0.0401). On the basis of sex and in small breed dogs, no significant differences were noted. In dogs with CKD stage 2, alpha klotho values were significantly lower (p = 0.0135) than in healthy dogs. Within the studied population, a reference interval for urinary klotho to creatinine ratio (UrKl/Cr) was determined in the range of 3.94-23.55 pg/gCr. Since our findings show that alpha klotho is associated with older age, we assume that this may have influenced the results in the group of dogs with CKD stage 1 due to the presence of predominantly old dogs in this group. Future studies would be needed to consider age as a factor affecting urinary alpha klotho in dogs with CKD.

The use of serum paraoxonase-1 to assess inflammation in horses with colitis.

Paraoxonase-1 (PON-1) has been suggested as a marker of inflammation and oxidative stress in horses and could potentially be used for prognostication in horses with colitis. Assessment of PON-1 in horses with colitis and comparison of two methods. Serum PON-1 was measured by two methods (paraoxon and p-nitrophenyl acetate) in 161 horses with colitis and 57 controls. Follow-up samples obtained during hospitalization were available from 106 horses with colitis. The two methods were compared. Serum PON-1 was significantly lower in horses with colitis than in healthy horses (P < .0001 for both methods) as well as in nonsurvivors compared with survivors (P = .0141 [paraoxon-based method] and P < .0001 [p-nitrophenyl acetate-based method]), but with marked overlap between groups. PON-1 activity did not change parallel to a change in inflammatory status in response to treatment when assessed at admission and in up to seven follow-up samples. Admission PON-1 activity could not reliably classify horses as survivors or nonsurvivors, with sensitivity and specificity ranging between 53.1% and 72.9%. Results from the two methods were comparable. Both methods reliably measured serum PON-1 activity. Significant differences in PON-1 activity were found between healthy horses and horses with colitis and between survivors and nonsurvivors. However, PON-1 activity varied considerably within groups. Both the proposed reference intervals as well as alternative cutoff values resulted in suboptimal diagnostic and prognostic performance, and the use of serum PON-1 in horses with colitis thus seems to add little to existing diagnostic and prognostic markers.

Reference limits for blood gas analysis performed from coccygeal vessels of multiparous Holstein dairy cows: Effects of stage of lactation and season of sampling

Blood gas analysis is a great support to the diagnostic process of critically ill patients. Its correct application to the medicine of dairy cows depends on the availability of specific reference intervals that are still difficult to find in the literature. They may vary according to the type of blood sampled, animals' age and production stage, and climatic conditions. This study aimed at calculating the reference limits for some blood gas parameters in the blood collected from the coccygeal vessels of multiparous Holstein dairy cows. This site of sampling implies the risk of withdrawing blood of unknown origin (venous, arterial, or mixed), but has a high practical interest for the easy and quick performance and the minimal animal restraint required. Data from 379 cows were used, and reference limits were produced for pH, partial pressure of carbon dioxide (pCO2), bicarbonate concentration (HCO3), total carbon dioxide concentration (tCO2), oxygen saturation (sO2), hemoglobin (Hb), hematocrit (Hct), base excess (BE), glucose, Na, K, and ionized calcium (iCa). The effects of stage of lactation (5 to 60 vs. > 60 DIM) and season of sampling (cold vs. hot) were investigated, and specific reference limits were produced for each variable and each level of the factors whenever a significant effect was detected. The pH, sO2, K, and iCa were not influenced by season or stage of lactation. All the other blood gas parameters were significantly affected by season of sampling, and Hb, Hct, glucose, and Na were also affected by stage of lactation. Reference limits provided in this study are specific to the site of sampling (coccygeal vessels) and the animal category considered. Further studies are needed to produce reference intervals for other blood gas parameters, cow categories, and blood types.

The time course of lactate and endocrine changes in dogs suffering from dog bite wounds.

The stress response after acute trauma in humans and animals has been well-recognised in the literature. However, data on temporal changes in endocrine parameters after acute trauma in previously healthy dogs are scant. To longitudinally track endocrine variables and lactate concentrations in dogs with canine bite wounds. Prospective study involving 20 dogs hospitalised after being bitten by another dog. Serum cortisol, thyroxine (total T4), thyrotropin (TSH), and lactate concentrations were measured on admission and every 8 hours after the recorded bite incident, for a 72-hour period. Median cortisol concentration was markedly elevated on admission (314.6 nmol/L; IQR 229.3-369.6) but returned to within the reference interval by 16 hours post-bite (99.5 nmol/L; IQR 48.7-225.4) and reached a nadir at 48 hours post-bite (38.5 nmol/L; IQR 32.1-115.9). Median total T4 concentration was within the reference interval on admission (20.6 nmol/L; IQR 12.7-27.9) but decreased below the reference interval by 8 hours (11.0 nmol/L; IQR 5.0-14.1) and reached a nadir 16 hours postbite (7.0 nmol/L; IQR 2.9-19.7), before gradually increasing after 64 hours to reach the reference range by 72 hours. The median TSH concentrations remained within the reference interval throughout the study period. Median lactate concentration was mildly elevated on admission (3.0 mmol/L; IQR 2.0-3.9). This study produced novel data on the temporal relationships of the hypothalamic-pituitary-adrenal and hypothalamicpituitary- thyroidal axes alterations after an acute traumatic insult in dogs.

Field measurement study of indoor thermal environment of badminton halls in a hot summer and cold winter region in different seasons in China

The indoor thermal environment has a direct impact on human thermal comfort and health. In order to assess the status of the indoor thermal environment of typical sports buildings in hot summer and cold winter climate zones in China, 14 badminton halls in 10 cities in Hubei Province (including 5 venues in Wuhan) in this climate zone are chosen as research objects for field testing of indoor thermal environment parameters in 4 seasons. All the tested stadiums are naturally ventilated in non-event conditions. The results reveal that the average indoor temperature of badminton halls in summer is excessively high (i.e., 31.89 °C), which is higher than the regulation specified in JGJ31-2003 or GB-T18883-2022 on the reference interval of the indoor air temperature of venues in summer, (i.e., (26–28 °C) or (22–28 °C), respectively). The average indoor temperature of badminton halls in winter is too low (i.e., 12.95 °C), and it is lower than the recommendations of JGJ31-2003 or GB-T18883-2022 on the reference interval of the indoor air temperature of venues in winter (i.e., (16–18 °C) or (16–24 °C), respectively), relative humidity and air velocity are in the thermal comfort interval for all seasons, and the indoor thermal environment factors of badminton courts in spring and autumn meet the comfort requirements. The indoor and outdoor temperatures and the relative humidity of badminton courts are highly correlated. The indoor temperature and relative humidity vary according to changes in those factors outdoors, whereas the air velocity is not affected by outdoor changes. In the hot summer and cold winter climate zones, some discrepancies in the indoor temperature variation patterns of badminton halls at various altitudes are detectable. The results of this study aim to provide a solid basis for the development of indoor thermal-comfort standards for sports stadiums in China.

Reference interval of free light chains ratio in patients with end-stage renal disease on chronic hemodialysis.

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Single intravenous and oral dose pharmacokinetics of the antiseizure medication brivaracetam in healthy cats.

The number of available antiseizure medications with demonstrated efficacy in cats is limited. As such, there is a need to evaluate the pharmacokinetics of newer medications so that proper dosing regimens can be made. Brivaracetam (BRV) is a more potent analogue of levetiracetam, and is Food and Drug Administration approved for use in people. The goal of this study was to describe the pharmacokinetics of intravenous and oral doses of BRV in healthy cats. A cross-over study involving eight healthy cats, that were administered 10 mg of BRV intravenously as a bolus and orally in the fasted state. Blood samples were collected over 24 h. Analysis was performed using liquid chromatography-mass spectrometry. Data were subjected to non-compartmental analysis. Median (min-max) of maximal concentration, time to maximal concentration, area under the curve, elimination half-life and oral absolute bioavailability were 902 (682-1036) ng/mL, 0.6 (0.5-2.0) h, 6.4 (5.2-7.2) h, 8145 (6669-9351) ng × h/mL and 100% (85-110) respectively. BRV appeared to be well tolerated by all cats. A single dose of BRV is well tolerated both orally and intravenously. Maximal concentrations are produced rapidly and within the human reference interval considered to be therapeutic.

Towards Personalized TSH Reference Ranges: A Genetic and Population-Based Approach in Three Independent Cohorts.

Background: Serum thyroid-stimulating hormone (TSH) measurement is the diagnostic cornerstone for primary thyroid dysfunction. There is high inter-individual but limited intra-individual variation in TSH concentrations, largely due to genetic factors. The currently used wide population-based reference intervals may lead to inappropriate management decisions. Methods: A polygenic score (PGS) including 59 genetic variants was used to calculate genetically determined TSH reference ranges in a thyroid disease-free cohort (n = 6,834). Its effect on reclassification of diagnoses was investigated when compared to using population-based reference ranges. Next, results were validated in a second independent population-based thyroid disease-free cohort (n = 3,800). Potential clinical implications were assessed in a third independent population-based cohort including individuals without thyroid disease (n = 26,321) as well as individuals on levothyroxine (LT4) treatment (n = 1,132). Results: PGS was a much stronger predictor of individual TSH concentrations than FT4 (total variance in TSH concentrations explained 9.2-11.1% vs. 2.4-2.7%, respectively) or any other nongenetic factor (total variance in TSH concentrations explained 0.2-1.8%). Genetically determined TSH reference ranges differed significantly between PGS quartiles in all cohorts, while the differences in FT4 concentrations were absent or only minor. Up to 24.7-30.1% of individuals, previously classified as having subclinical hypo- and hyperthyroidism when using population-based TSH reference ranges, were reclassified as euthyroid when genetically determined TSH reference ranges were applied. Individuals in the higher PGS quartiles had a higher probability of being prescribed LT4 treatment compared to individuals from the lower PGS quartiles (3.3% in Q1 vs. 5.2% in Q4, Pfor trend =1.7 × 10-8). Conclusions: Individual genetic profiles have the potential to personalize TSH reference ranges, with large effects on reclassification of diagnosis and LT4 prescriptions. As the currently used PGS can only predict approximately 10% of inter-individual variation in TSH concentrations, it should be further improved when more genetic variants determining TSH concentrations are identified in future studies.

Reference Intervals of Mass Coefficients and Absolute Weights of Mini Pigs’ Organs

Introduction. Measurement of weights and calculation of mass coefficients of the laboratory animals’ internal organs are the integral stages of toxicological research. However, the absence of the correct intra-laboratory reference intervals corresponding to the normal values established for the animal population of a research laboratory could hinder the analysis of the mass coefficient changes in the experiment. For example, the data on weights and mass coefficients of mini pigs’ organs is being an issue due to its insufficient availability in the open sources. At the same time, in the literature there is a lot of such kind of data referring to the industrial pig breeds. Due to the wide use of the mini pigs in the pre-clinical research and because in the pig species taxonomy they are considered to be a weight category representing the pigs with reduced mass of the body with similar morphology of the organs and body systems, we have set an objective to determine and calculate the reference intervals of mass coefficients of internal organs relative to the mass of the body and brain, as well as the absolute weights of mini pigs’ internal organs and compare the results with the data on mini and industrial pig breeds in the literature sources.Materials and Methods. The data on 29 males and 29 females of the Vietnamese lop-bellied mini pig breed aged 6 months and older, who used to be in control groups of the various experiments held at JSC “SPA “House of Pharmacy” (Leningrad region) in the period from January 2018 to March 2024, was used to calculate the reference intervals. The statistical analysis was peRussian Federationormed using Microsoft Excel and Reference Value Advisor v2.1 software in compliance with the CLSI guidelines. Calculation of the reference intervals for all parameters was carried out by a robust method, the compliance with the normal distribution law was determined by Anderson–Darling test, in case of abnormal distribution of data, calculation of the reference interval was carried out with the Box–Cox transformation.Results. The data on the absolute weights of organs and their coefficients relative to the body and brain masses were presented in the form of the lower and upper reference limits and confidence intervals for each of the limit. The reference intervals of masses of organs across all parameters in males and females had similar limits, the most comparable values were found for the heart and brain parameters. The calculated interval of the heart absolute weight in males was 28.3–253 g, that of the brain was 46.5–93.7 g; in females these intervals were 42.9–279 g and 55.5–81.8 g respectively. Upon comparing the obtained data with the literature sources, it was found that the majority of the absolute weights of all measured mini pigs’ organs had fitted in the limits of the reference values, whereas the masses of the lungs and liver were at the lower limit or below the calculated intervals. The values of the absolute weights of most of the organs of the industrial pig breeds were higher than that of mini pigs, which was due to the difference in the body size and mass of the studied animal breeds. When comparing the mass coefficients of organs in relation to the body mass, it was found that the coefficients of most organs of the industrial breeds and mini pigs, on the contrary, were within the calculated reference intervals or slightly exceeded them.Discussion and conclusion. The calculated reference intervals of the mass coefficients of some organs in relation to the body mass, as well as the absolute weights of the spleen in mini pigs are comparable with the data available in literature for the industrial meat pig breeds. At the same time, the data available in the literature sources on the absolute weights of organs and their mass coefficients relative to the body mass of mini pigs, in most cases, have fitted into the calculated intervals. To increase the prognostic value of the obtained reference intervals, the analysis of a larger size sample is necessary.

Interference by vitamin B12-macrocomplexes: towards an effective detection and correct interpretation of hypo- and hypervitaminemia

Abstract Objectives The presence of macro-B12 is a cause of factual hypervitaminemia B12. Precipitation with polyethylene glycol (PEG) is a simple method of removing high-molecular-weight biomolecules. However, “free” molecule may co-precipitate. This fact imposes the need to establish new reference values for the post-precipitation result. The main aims of the study were to (Baeza I, Corchón A, Pérez JM, Remacha AF, Rocha H, Rodríguez-Portugal E, et al. Basic Aspects of vitamin B12. In: Communication Committee of the Spanish Society of Laboratory Medicine (SEQCML). Clinical significance of vitamin B12 deficiency. Beyond megaloblastic anemia; 2022. ISBN: 978-84-89975-60-6): establish post-PEG reference intervals (RIs) for total vitamin B12 (Iqtidar N, Chaudary MN. Misdiagnosed vitamin B12 deficiency a challenge to be confronted by use of modern screening markers. J Pak Med Assoc 2012;62:1223–9); compare the two bibliographic criteria for defining the presence of macro-B12 (Green R. Vitamin B12 deficiency from the perspective of a practicing hematologist. Blood 2017;129:2603–11); evaluate the joint usefulness of percentage post-PEG vitamin B12 recovery and post-PEG RIs to inform the real vitamin B12 status; and (Carmel R. Diagnosis and management of clinical and subclinical cobalamin deficiencies: why controversies persist in the age of sensitive metabolic testing. Biochimie 2013;95:1047–55), propose interpretative comments for ease of interpretation. Methods Prospective study in which 488 serum samples from “healthy” individuals were included and analyzed to determine recovery and RIs following PEG precipitation. Subsequently, a retrospective analysis was carried out in order to evaluate the joint usefulness of both definitions for a suspicion of macro-B12. A total of 297 cases were included. Results Recovery and post-PEG RIs determined on an Alinity i platform ranged from 60 to 107 % and from 118 to 506 pmol/L, respectively. McNemar’s test revealed statistically significant differences between both criteria for estimating interference. However, both methodologies showed good agreement. In 27 cases, the presence of macro-B12 coexisted with true hypervitaminemia B12. No case of coexistence of macro-B12 with vitamin B12 deficiency was detected in our series. Conclusions Laboratory reports should include total vitamin B12 concentration, recovery and post-PEG vitamin B12 concentration with their adjusted RIs to better assess the body vitamin status.

Coagulation Profile of the Healthy Miranda's Donkey.

Miranda's donkey, originating in northern Portugal, is an autochthonous breed that is deeply intertwined with the region's culture and economy. Knowledge of the physiological characteristics of the breed is important for its preservation, and several studies have been carried out, but none have focused on its coagulation profile. The aim of this study was to establish reference intervals (RIs) for coagulation in healthy Miranda's donkey and to assess the influence of sex and age. Blood samples from 75 clinically healthy animals were analyzed for seven coagulation parameters: four using IDEXX ProCyte Dx and three using Start® 4-Diagnostica-Stago. The RI values were calculated following the ASVCP guidelines and with the Reference Advisor V.2.1 software. To analyze the influence of sex and age, SPSS version 29 was used. No significant differences were found between sexes (p > 0.05), but statistically significant differences were found between ages (p < 0.05) for platelet count and plateletcrit (both higher in young animals). The RIs described here can help monitor health and guide the diagnosis and treatment of diseased Miranda's donkeys, contributing to their preservation. Our study encourages further research on coagulation in donkeys and the use of different methodologies to obtain information for veterinarians working with this species.

Complete Blood Count and Biochemistry Reference Intervals for Healthy Adult Donkeys in the United States.

Previous hematologic and serum biochemistry reference interval (RI) values have been established for donkeys in various geographic regions, life-stages, or for specific donkey breeds. The last extensive investigation establishing RIs for adult donkeys in the United States (U.S.) was published over three decades ago. We aimed to establish updated robust RIs using a reference population of apparently healthy adult donkeys from across the U.S. Standard sized (n = 102), miniature (n = 17), and mammoth (n = 1) donkeys from four different states were enrolled, with 20% of the study population including donkeys captured directly from the wild in Death Valley National Park, CA. RIs were established in accordance with the American Society for Veterinary Clinical Pathology and Clinical Laboratory Standards Institute guidelines. The findings will assist practitioners with the interpretation of their complete blood count and biochemistry panel results in U.S. donkeys. This study also highlights a comparison of results for some important analytes in U.S. donkeys compared to U.S. horses and previously established donkey RIs.

Comparison of 2 Serum Free Light Chain Assays with Creatinine Normal and Abnormal Populations Demonstrates the Need for Standardization.

The objective of this study was to compare The Binding Site's Freelite on Optilite and Diazyme's Kappa/Lambda free light chains (K/L FLC) on Abbott Architect c8000 with healthy and renal insufficient populations and to evaluate their respective reference intervals for serum free light chains (sFLCs). Two hundred sixty serum samples were measured for creatinine and sFLCs by both assays and a subset by immunofixation electrophoresis. Verification of manufacturer-defined reference intervals was assessed. Kappa free light chains (KFLC) showed excellent correlation of 0.998 R2 with a slope of 0.73. For Lambda free light chains (LFLC), an acceptable correlation of 0.953 R2 was found with a slope of 1.50 as well as a skewness-based difference with a -12.70 intercept. Healthy estimated glomerular filtration rate (eGFR) ≥60 reference interval verification of central 95% could not be confirmed for either Freelite or Diazyme although LFLC was much closer than KFLC for both assays with Freelite KFLC recovering only 37% of values within reference interval claims. The K/L FLC ratio did not meet 100% claim for both Freelite (91%) and Diazyme (95%) among those with eGFR ≥60. Samples with eGFR ≤59 had increasingly higher levels of KFLC and LFLC for both assays. When comparing worsening eGFR status, Freelite recovered increasingly higher ratios while Diazyme recovered increasingly lower ratios. Healthy reference intervals could not be verified for either Freelite or Diazyme. Renal reference intervals for Freelite are currently warranted while they are not recommended for Diazyme. The differences between these 2 assays can be minimized by standardization efforts such as recalibration.

Reference intervals and percentiles for soluble transferrin receptor and sTfR/log ferritin index in healthy children and adolescents.

Soluble transferrin receptor (sTfR) is a marker of both erythropoiesis and iron status and is considered useful for detecting iron deficiency, especially in inflammatory conditions, but reference intervals covering the entire pediatric age spectrum are lacking. We studied 1,064 (48.5 % female) healthy children of the entire pediatric age spectrum to determine reference values and percentiles for sTfR and the ratio of sTfR to log-ferritin (sTfR-F index) using a standard immunoturbidimetric assay. Soluble TfR levels were highly age-specific, with a peak in infancy and a decline in adulthood, whereas the sTfR-F index was a rather constant parameter. There were positive linear relationships for sTfR with hemoglobin (Hb) (p=0.008) and transferrin (females p<0.001; males p=0.003). Anegative association was observed between sTfR and ferritin in females (p<0.0001) and for transferrin saturation and mean corpuscular volume (MCV) in both sexes (both p<0.0001). We found a positive relationship between sTfR and body height, body mass index (BMI) and inflammatory markers (CrP p<0.0001; WBC p=0.0172), while sTfR-F index was not affected by inflammation. Soluble TfR values appear to reflect the activity of infant erythropoiesis and to be modulated by inflammation and iron deficiency even in a healthy cohort.

On-Field Rule Out of Mild Traumatic Brain Injury: Can Blood-Based Biomarker Testing Change Outcome of Major Sporting Events?

Mild traumatic brain injury (mTBI) is defined as a Glascow Coma Score of between 13 and 15. The diagnosis and rule out of individuals suffering from mTBI on an acute basis is imperfect and involves subjective measures. Serum biomarkers that exhibit narrow within-individual biological variation can be used for the early rule-out of mTBI, when baseline levels are compared during health. This is a descriptive study that applies published biological variation data of serum mTBI biomarkers for early rule out of sports-related injury. Laboratory tests such as glial fibrillary acidic protein, fatty acid binding protein 7, and phosphorylated protein enriched in astrocytes have low within-individual variances and are potential candidates. Aldolase C also rises early in blood but the biological variation is of this marker is currently unknown. The use of blood-based biomarkers, measured in real time using point-of-care testing devices when compared to a pre-competition baseline instead of a population-based reference interval, can provide early rule out of mTBI, and possibly enable on-field evaluations and a medical decision for a return to competition.

Accounting for differences between serum and plasma: An indirect approach to derive reference intervals for total protein, albumin, and globulin

BackgroundObservable quantitative variations exist between plasma and serum in routine protein measurements, often not reflected in standard reference intervals. In this study, we describe an indirect approach for estimating a combined reference interval (RI) (i.e., serum and plasma), for commonly ordered protein measurands: total protein, albumin, and globulin. MethodsWe applied an indirect reference interval estimation for protein measurements in serum and plasma using data from July 2018 to February 2024. The data were divided into three Epochs based on a period of plasma separator tube shortage during the COVID-19 pandemic. Bootstrap resampling was used to calculate RIs and corresponding 95% confidence intervals for each month. ResultsOur results demonstrate notable changes in RI limits for total protein, albumin, and globulin between Epochs, reflecting the influence of changing sample matrix. A combined RI was identified for all components and verified using plasma and serum samples from 20 healthy individuals and retrospective analysis of flagging rates on our outpatient population using new and historical RIs. ConclusionThe study demonstrates notable differences in the RIs for total protein, albumin, and globulin when container type changes. In addition, the results demonstrate the effectiveness of big data analytics in deriving RIs and highlights the necessity of continuous RI assessment and adjustment based on the patient population and acceptable specimen types.