Upper Limit Of Reference Interval Research Articles

Reporting of Hyperprolactinaemia Post-polyethylene Glycol (PEG) Precipitation at Hospital Tengku Ampuan Rahimah Klang, Malaysia

Introduction: Macroprolactinaemia is defined as hyperprolactinaemia due to excess macroprolactin in the presence of normal monomeric prolactin. Failure to identify macroprolactinaemia may result in patients being subjected to unnecessary investigations and inappropriate treatment for hyperprolactinaemia. In our centre, screening for macroprolactinaemia is currently performed at the request of the treating physician. The study thus aimed to determine the frequency of macroprolactinaemia in samples with serum prolactin ≥700 mIU/L in Hospital Tengku Ampuan Rahimah (HTAR) and to determine the presence of true hyperprolactinaemia in these cases. Methods: A cross-sectional study among hyperprolactinaemic subjects in HTAR, using serum specimens received by the laboratory for measurement of prolactin between October 2018 and September 2019. Samples with prolactin ≥700 mIU/L were screened for macroprolactinaemia using the polyethylene glycol (PEG) precipitation technique. Macroprolactinaemia was present when the percentage recovery of prolactin post-PEG was <40%. Assay-specific post-PEG monomeric prolactin levels were also reported, with levels above the upper limit of reference intervals indicated the presence of true hyperprolactinaemia. Results: A total of 101 samples were subjected to PEG precipitation. Macroprolactinaemia was found in four (4%) samples, whilst eight (7.9%) were categorised as indeterminate (percentage recovery of 40-60%). The remaining 89 (88.1%) samples had a percentage recovery >60%, hence considered negative for macroprolactinaemia. All four samples with macroprolactinaemia also had raised monomeric prolactin levels indicating the co-existence of macroprolactinaemia in subjects with true hyperprolactinaemia. Similarly, in the indeterminate group, all eight had raised monomeric prolactin levels. Conclusion: In one-year period in HTAR, macroprolactinaemia was detected in 4% of subjects with prolactin ≥700 mIU/L, all of whom also had raised monomeric prolactin levels. The common occurrence of both macroprolactinaemia and true hyperprolactinaemia warrants the reporting of both percentage recovery and monomeric prolactin levels post-PEG.

Method Validation and Establishment of Reference Intervals for an Insulin-like Growth Factor-1 Chemiluminescent Immunoassay in Cats.

Previously, radioimmunoassay (RIA) has been the only assay to measure insulin-like growth factor-1 (IGF-1) to diagnose hypersomatotropism (HS). Due to radiation concerns, availability, and the cost of IGF-1 RIA, validation of assays for automated analysers such as a chemiluminescent immunoassay (CLIA) is needed. The aim of this study was to validate a CLIA for measurement of feline IGF-1 (IMMULITE 2000® XPi, Siemens Medical Solutions Diagnostics, Malvern, PA, USA) compared to IGF1 RIA, establish reference interval (RI), and determine a cut-off value for diagnosis of HS in diabetic cats. Validation of assay performance included precision, linearity, and recovery studies. Right-sided RI was determined using surplus serum of 50 healthy adult cats. Surplus serum samples of diabetic cats with known IGF-1 concentration with (n = 32/68) and without HS (n = 36/68) were used for method comparison with RIA. The cut-off for diagnosis of HS was established using receiver operating characteristic (ROC) analysis. The intra-assay coefficient of variation (CV) was ≤4.7%, and the inter-assay CV was ≤5.6% for samples with low, medium, and high IGF-1 concentration. Linearity was excellent (R2 > 0.99). The correlation between CLIA and RIA was very high (rs = 0.97), with a mean negative bias for CLIA of 24.5%. The upper limit of RI was 670 ng/mL. ROC analysis showed an area under the curve of 0.94, with best cut-off for diagnosis of HS at 746 ng/mL (sensitivity, 84.4%; specificity, 97.2%). The performance of CLIA was good, and the RI and cut-off for HS diagnosis established in this study allow for CLIA to be used in routine work-up of diabetic cats.

Kidney Involvement in Pediatric COVID-19 Cases: A Single-Center Experience.

Objective:The kidney is the second most commonly affected organ by severe acute respiratory syndrome coronavirus-2, characterized by hematuria, proteinuria, and acute kidney injury. There are few studies describing renal involvement in pediatric cases.Materials and Methods:This retrospective study evaluated the prevalence of hematuria, proteinuria, and acute kidney injury in severe acute respiratory syndrome coronavirus-2-positive pediatric cases (1-18 years old) who visited emergency department between March and November 2020. Patients with urinary tract infections were excluded. An age-specific upper limit of reference interval was used to define “elevated serum creatinine” (greater than upper limit of reference interval) and acute kidney injury (>1.5 times upper limit of reference interval).Results:A total of 228 patients were evaluated, median age was 12.7 years (interquartile range: 7.5; 16.1), and 51.3% were male. The prevalence of asymptomatic, mild, and moderate-to-severe disease was 12.7% (29/228), 77.2% (176/228), and 10.1% (23/228), respectively. The prevalence of hematuria, proteinuria, and elevated serum creatinine was 15.8% (36/228), 6% (14/228), and 3% (7/228), respectively. Kidney involvement (i.e., at least 1 of these findings) was 23.2% (53/228) and significantly higher in the moderate-to-severe disease (43.5%). None of the patients met the acute kidney injury criterion. In logistic regression analysis, female sex (odds ratio: 1.97, 95 CI%: 1.03; 3.70, P = .040) and fever (odds ratio: 2.28, 95% CI: 1.19; 4.36, P = .012) were independent predictors of kidney involvement. Three patients demonstrated a kidney presentation (macroscopic hematuria) on admission, and another patient was diagnosed with C3 glomerulonephritis during hospitalization.Conclusion:Kidney involvement was found about in 1 quarter of children with coronavirus disease 2019. Awareness and recognition of kidney involvement and follow-up are important in the management.

Impact of Sex and Cardiovascular Risk Factors on Myocardial T1, Extracellular Volume Fraction, and T2 at 3 Tesla: Results From the Population-Based, Hamburg City Health Study.

Reliable reference intervals are crucial for clinical application of myocardial T1 and T2 mapping cardiovascular magnetic resonance imaging. This study evaluated the impact of sex and cardiovascular risk factors on myocardial T1, extracellular volume fraction (ECV), and T2 at 3T in the population-based HCHS (Hamburg City Health Study). The final study sample consisted of 1576 consecutive HCHS participants between 46 and 78 years without prevalent heart disease, including 1020 (67.3%) participants with hypertension and 110 (7.5%) with diabetes. T1 and T2 mapping were performed on a 3T scanner using 5b(3b)3b modified Look-Locker inversion recovery and T2 prepared, fast-low-angle shot sequence, respectively. Stepwise regression analyses were performed to identify variables with an independent impact on T1, ECV, and T2. Reference intervals were defined as the interval between the 2.5% and 97.5% quantiles. Sex was the major independent influencing factor of myocardial native T1, ECV, and T2. Female patients had significantly higher upper limits of reference intervals for native T1 (1112-1261 versus 1079-1241 ms), ECV (23%-33% versus 22%-32%), and T2 (36-46 versus 35-45 ms) compared with male patients (all P<0.001). Cardiovascular risk factors, such as diabetes and hypertension, did not systematically affect native T1. There was an independent association of T2 by hypertension and, to a lesser degree, by left ventricular mass, heart rate (all P<0.001), and body mass index (P=0.001). Sex needs to be considered as the major, independent influencing factor for clinical application of myocardial T1, ECV, and T2 measurements. Consequently, sex-specific reference intervals should be used in clinical routine. Our findings suggest that there is no need for specific reference intervals for myocardial T1 and ECV measurements in individuals with cardiovascular risk factors. However, hypertension should be considered as an additional factor for clinical application of T2 measurements. URL: https://www. gov; Unique identifier: NCT03934957.

Postoperative Vitamin Profile after Receiving a Novel Peripheral Parenteral Nutrition Solution: Multicenter Randomized Controlled Phase III Trial

Introduction: We assessed the efficacy and safety of OPF-105, a novel all-in-one peripheral parenteral nutrition (PPN) solution containing multivitamins by the U.S. Food and Drug Administration in 2000 (FDA2000 recommendation). Methods: We conducted a phase III trial administering OPF-105 or BFL (combination of a commercially available PPN solution and fat emulsion) to patients after gastrointestinal (GI) tract surgery from postoperative day (POD) 1 up to POD14. Until POD7, nutrients were provided only with OPF-105 or BFL. After blood sampling on POD8, oral food intake was permitted. PPN was administered according to the amount of food intake. Results: Efficacy endpoints were assessed in 99 subjects (OPF group: 52; BFL group: 47). The levels of blood proteins and fatty acids in the two groups were similar on POD8. The transition of these mean levels was similar in both groups from POD1 or 2 to POD9 to 15. The mean preoperative blood vitamin levels were within reference intervals (RIs). On POD1 (before administration), the mean levels of most blood vitamins decreased compared to those of the preoperative levels. In the BFL group, the mean blood levels of vitamin B2, B6, pantothenic acid (PA), folic acid (FA), biotin, and C decreased below or near the lower limit of RIs on POD8, and the mean blood levels of vitamin B6 and C remained low from POD9 to 15. In the OPF group, the mean blood levels of vitamins, excluding vitamin K, were within RIs on POD8 and POD9 to 15. The mean levels of blood vitamin K increased over the upper limit of RIs on POD8 but within RIs from POD9 to 15. There was no obvious difference in the incidence of adverse events between the two groups, which is common after GI tract surgeries. Conclusion: Blood vitamin levels decreased when patients were administered PPN without vitamin supplementation during the first week after surgery. The novel PPN formula containing multivitamins recommended by FDA2000 can be safely administered to postoperative patients to maintain blood vitamin levels.

Determination of diagnostic threshold in harmonization and comparison of clinical utility for five major antiphospholipid antibody assays used in Japan.

Anticardiolipin antibodies (aCL) and anti-β2 -glycoprotein I antibodies (aβ2 GPI) are essential in diagnosing antiphospholipid syndrome (APS) according to the international APS guideline. Five commercial assays for aCL and aβ2 GPI are available in Japan, but their test results are quite discordant. For harmonization of diagnosing APS, upper reference limit (URL) and diagnostic accuracy of each assay were evaluated and compared by testing common sets of specimens across all assays. We evaluated two manual and three automated assays for aCL and aβ2 GPI of IgG- and IgM classes. 99%URL (the upper limit of reference interval: as per guideline) together with 97.5%URL were determined by testing sera from 198 to 400 well-defined healthy subjects. Both URLs were compared with the cutoff values, which were determined based on ROC analysis by testing 50 each of plasma specimens from patients with/without APS. Diagnostic accuracy was evaluated as area under curve (AUC) of the ROC curve. A variable degree of discrepancy between URLs and the cutoff values was observed, which was partly attributable to between-year assay variability. 97.5%URLs were set lower and closer to the cutoff values than 99%URLs. For all assays, diagnostic accuracies of both aβ2 GPI-IgG and aCL-IgG were generally high (AUC: 0.84-0.93); whereas those for IgM-class assays were low (AUC: 0.57-0.67), implicating its utility is limited to rare IgG negative APS cases. To ensure harmonized APS diagnosis, the diagnostic thresholds of the five assays were evaluated by common procedures. Contrary to the guideline, 97.5%URL is rather recommended for diagnosing APS, which showed a closer match to the cutoff value.

Acute kidney injury in paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is not associated with progression to chronic kidney disease

BackgroundPaediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) is a rare complication of SARS-CoV-2 associated with single or multiorgan dysfunction.ObjectiveWe aimed to evaluate the incidence of acute kidney injury...

Establishment of the reference interval for high-sensitivity cardiac troponin T in healthy children of Chongqing Nan’an district

Objective To detect the concentration of high-sensitivity cardiac troponin T (hs-cTnT) in healthy children aged 0–14 years by electrochemiluminescence immunoassay (ECLIA), so as to explore the differences in different ages and genders. The aim of this study is to establish the reference interval for hs-cTnT in healthy children aged 0–14 years. Methods After screening, 3463 healthy children, including 1924 boys and 1539 girls, were selected from 4617 children aged 0–14 years. They were divided into nine groups: one day (umbilical cord blood; ‘UCB’), one day (venous blood; ‘VB’), 2–28 days, 29 days–<3 months, 3–<6 months, 6 months–<1 year old, 1–< 3 years old, 3–< 6 years old and 6–14 years old. A nonparametric test was used to detect the hs-cTnT concentration. The upper limit of the reference interval is the mean of the 99th percentile after bootstrap sampling. Results Hs-cTnT levels conformed to a non-Gaussian distribution. There was no significant difference in the concentration of hs-cTnT between boys and girls in the general data, but there were differences between boys and girls in the 3–<6 years old and 6–14 years old age groups. Except for UCB and 2–28 days, the concentration of hs-cTnT was significantly different in other age groups. The level of hs-cTnT in neonatal serum (2–28 days) was the highest. In other groups, it decreased gradually with age and dropped to the reference range of adults (0–14ng/L) at one-year old. The upper limit of reference interval of hs-cTnT concentration in each group was, respectively, 60.8, 78.8, 96.6, 58.6, 34.2, 16.2, 11.4, 8.0 (7.8 female), and 7.9 (7.3 female) ng/L. Conclusions Referring to WS/T 402-2012 establishment of reference intervals for clinical laboratory testing projects and CLSI (Clinical and Laboratory Standards Institute) C28-A3 documents and the joint expert consensus of ESC (European Society of Cardiology) and ACC (American College of Cardiology) in 2007, we established the reference interval of hs-cTnT concentration in children aged 0–14 years in Chongqing Nan’an district of China which can provide certain reference value for clinical diagnosis and treatment of myocarditis and myocardial (micro) injury in children.

Age and seasonal variation and establishment of reference intervals for water-soluble vitamins determined by liquid chromatography tandem mass spectrometry

ObjectivesWe aimed to establish reference intervals for water-soluble vitamins determined by liquid chromatography tandem mass spectrometry to improve the diagnosis of vitamin deficiency and outcomes of associated conditions. MethodsIn this retrospective analysis of 24 810 specimens, we aimed to examine sex-, age-, and season-related variations in vitamin levels in different groups, set reference-value intervals for vitamin levels, and evaluate these reference values against those recommended by manufacturers. ResultsLevels of vitamins B3, B5, B6, B7, and B12 were higher, and those of vitamins B2, B9, and C were lower, in men than in women. There were seasonal variations in levels of vitamins B1, B3, B5, B6, B9, B12, and C. Levels of vitamins B1, B2, B3, B5, B6, B7, B9, and C differed across age groups; vitamin B1 displayed significant differences between ages 0 to 14 years and adults compared with reference change values. The lower limits of vitamins B1 (ages 15–100 y), B2, B3, B7, and C were lower, and that of vitamin B5 was higher, than the recommended reference values. Finally, the upper limits of vitamins B1, B3, B5, B6, and B7 were lower than the recommended values. ConclusionsFor values obtained using liquid chromatography tandem mass spectrometry, the lower limits of reference intervals for vitamins B1 (ages 15–100 y), B2, B3, B7, and C should be lowered, that of vitamin B5 should be raised, and the upper limits of reference intervals for vitamins B1, B3, B5, B6, and B7 should be lowered.

Oscillations of C-peptide in the euglycemic clamp and their effect on the pharmacodynamic assessment of insulin preparations.

C-peptide should be continuously suppressed. However, increased postdosing C-peptide is not an uncommon phenomenon in euglycemic clamp studies involving healthy participants. This study aimed to determine the extent to which the postdosing C-peptide increases from the baseline that could affect the accuracy of glucodynamics in euglycemic clamp studies involving healthy subjects. First, 10 healthy males underwent a 10-h euglycemic clamp without exogenous insulin administration to obtain a reference interval (RI) for the ratio of C-peptide after 0min (CPt ) to baseline C-peptide (CP0 ). Then, the data from a pharmacokinetic and pharmacodynamic study of insulin aspart (IAsp) were analyzed, and 70 eligible clamps were grouped by CPt /CP0 : group A ([CPt /CP0 ]max >upper limit of RI), group B (1<[CPt /CP0 ]max ≤upper limit of RI), and group C ([CPt /CP0 ]max ≤1). The differences in basal and clamped blood glucose, CPt /CP0 , and the pharmacokinetics and pharmacodynamics of IAsp were compared, and the relationship between elevated CPt and the accuracy of pharmacodynamics was analyzed. The RI of CPt /CP0 was 22.7%-152.1%; 1.5×baseline might be a ceiling for the increase in CPt under stable conditions. The maximum glucose infusion rate (GIR) in group A tended to be higher than that in group B or C (Pfor trend =0.033). The AUCGIR,0-10h in groups A, B, and C was 1983±650,1682±454, and 1479±440mg/kg (P=0.047), respectively, under comparable IAsp exposure. No intergroup difference was detected in clamped glucose, IAsp dose, or body mass index. In conclusion, postdosing C-peptide over 1.5× baseline indicates insufficient inhibition of endogenous insulin secretion, which could compromise the pharmacodynamics of insulin preparations.

Selective application of neuroendocrine markers in the diagnosis and treatment of small cell lung cancer

AimsHere, we explored the potential application and selection of neuroendocrine biomarkers in the diagnosis and treatment of small cell lung cancer. MethodsWe retrospectively analyzed 118 patients with small cell lung cancer (SCLC), 166 patients with non-small cell lung cancer (NSCLC), 33 patients with benign lung disease (BLD), and 200 healthy individuals admitted to Zhejiang Provincial People’s Hospital between January 1, 2015 and May 31, 2019. All the patients were newly diagnosed with either SCLC, NSCLC, or BLD and previously untreated. Peripheral blood levels of ProGRP, NSE, CEA, and CYFRA21-1 were analyzed during the follow-up treatment, and 2-fold upper limit of reference intervals were defined as effective elevation. We used paired results to analyze the diagnostic efficiency of proGRP and NSE on SCLC. ResultsIn the 118 SCLC patients, proGRP levels were significantly higher compared with NSE levels. The diagnostic efficiencies of NSE and ProGRP for SCLC were 0.8554 and 0.9053, respectively. The combined diagnostic efficiency (0.9426) was higher relative to NSE, but there was no significant difference compared with proGRP. The effective elevation rate of proGRP was 45.3% higher than that of NSE in the limited stage of SCLC. In the extensive disease of SCLC patients, 70.7% cases had more than 10-fold increase in proGRP value, whereas 56.9% cases had less than 5-fold increase in NSE value. Compared with pre-treatment, the median concentrations of proGRP increased by 204.0% higher than that of NSE (71.3%) in the progressive group. Besides, the dynamic change in imaging characteristics and tumor size had a strong correlation with the levels of proGRP. SignificanceProGRP is a reliable neuroendocrine biomarker in SCLC. The effective elevation of proGRP has a potential diagnostic and efficacy value in the evaluation of SCLC. However, the combined detection of proGRP and NSE does not significantly improve the diagnosis of lung cancer.

SUN-222 Pre- and Post-Pubertal Reference Ranges for Oxygenated Androgens in Saliva

Oxygenated androgens such as 11 β-hydroxyandrostenedione (11OHA4) and 11-ketotestosterone (11KT) contribute significantly to the androgen pool in humans and their measurement has been shown to be useful in diagnosing disorders such as polycystic ovarian syndrome or premature adrenarche and also in monitoring treatment of congenital adrenal hyperplasia, alongside the classical androgens. Their measurement in saliva is particularly advantageous due to the non-invasive nature of sampling, meaning samples can easily be taken regularly to monitor treatment; however reference range data is not currently available for 11OHA4 and 11KT, limiting their clinical use. These analytes were measured in saliva samples from pre and post-pubertal males and females to inform reference ranges for these analytes. Samples collected into salivettes as part of the PRIMMS study (Technische Universität Dresden) were used for this work. A total of 130 samples (35 from pre-pubertal females, 43 from post-pubertal females, 42 from pre-pubertal males and 20 from post-pubertal males) were analysed for 11OHA4 and 11KT by LC-MS/MS. The ages of the participants ranged from 3.77 to 14.0 years in the pre-pubertal samples and 13.9-17.9 years in the post-pubertal samples. Pubertal status was determined clinically. The upper cut-off of the reference interval for 11OHA4 was 560 pmol/L in pre-pubertal females and 590 pmol/L in males, whilst 11KT had an upper limit of 216 pmol/L in females and 205 pmol/L in males. The upper limits of the ranges were higher in post-pubertal samples, with ranges of up to 1542 pmol/L in females and 1775 pmol/L in males for 11OHA4; the ranges for 11KT were up to 654 pmol/L for post pubertal females and 585 pmol/L for post-pubertal males. The data shows, as expected, a rise in the 11 oxygenated androgens post puberty. The upper limits of reference intervals for both analytes were very similar in males and females both pre- and post pubertally. These data can be used to inform clinical interpretation of the 11-oxygenated androgens; further work is required with larger cohorts of samples to develop more robust reference ranges.

Biochemical testing for neuroblastoma using plasma free 3-O-methyldopa, 3-methoxytyramine, and normetanephrine.

Neuroblastoma, the most common extracranial solid tumor of childhood, produces catecholamines that are metabolized within tumor cells. Homovanillic acid (HVA) and vanillylmandelic acid (VMA), the end products of catecholamine metabolism, have limited accuracy for testing of the tumors. This study assessed whether metabolites produced in earlier steps of catecholamine metabolism might offer improved diagnostic accuracy over urinary HVA and VMA. Plasma concentrations of 3-methoxytyramine, normetanephrine, and metanephrine were measured in two pediatric cohorts: (i) 96 children with confirmed neuroblastoma and (ii) 41 children with signs and symptoms of a catecholamine-producing tumor or other neoplasms and in whom neuroblastoma was excluded. Additional measurements of plasma 3-O-methyldopa and relationships of metabolites to MYCN amplification were examined in patient subgroups. Overall, 94 of the 96 patients with neuroblastoma had concentrations of 3-methoxytyramine or normetanephrine above age-specific upper limits of reference intervals, providing a diagnostic sensitivity of 97.9% that was higher (P<0.0001) than that of 82.2% for HVA and VMA. One of the two patients with normal plasma results showed an elevation of plasma 3-O-methyldopa. Diagnostic specificities were, respectively, 95.1% and 84.8%. Areas under receiver-operating characteristic curves confirmed the superior diagnostic power of the plasma than the urinary test (0.994 vs 0.945; P=0.0095). Ratios of plasma 3-methoxytyramine to normetanephrine were 7.2-fold higher (P<0.0001) for patients who had neuroblastomas with MYCN amplification than without MYCN amplification. Measurements of plasma 3-methoxytyramine and normetanephrine provide a highly accurate diagnostic test for neuroblastoma and also offer potential for prognostic risk stratification.

Retrospective evaluation of a local protocol used to enhance laboratory savings through minimizing the performance of alkaline phosphatase isoenzyme analysis.

Alkaline phosphatase isoenzyme analysis is an expensive and time-consuming laboratory test. We evaluated the effect of a locally derived screening algorithm for alkaline phosphatase isoenzyme requests on the number of alkaline phosphatase isoenzyme analyses performed, laboratory cost and patient care. A total of 110 alkaline phosphatase isoenzyme analysis requests from the year 2015 were reviewed and subsequent alkaline phosphatase concentrations were monitored over a two-year period, to determine if the decision of performing/not performing alkaline phosphatase isoenzyme analysis, based on the algorithm, had an impact on patient care and laboratory cost. All alkaline phosphatase isoenzyme analysis requests with two consecutive elevated alkaline phosphatase concentrations (>upper limit of reference interval) were screened and, subject to the gamma glutamyl transferase being within the reference interval, either Bone alkaline phosphatase or 25 hydroxyvitamin D was measured depending on the age of the patient. Compliance with this algorithm led to the normalization of subsequent serum alkaline phosphatase in 97% of patients without requiring alkaline phosphatase isoenzyme analysis. The cost of performing Bone alkaline phosphatase and 25 hydroxyvitamin D in-house was £778.50, while the cost of performing alkaline phosphatase isoenzyme analysis would have been £3040. This resulted in a laboratory saving of £2261.50. Implementation of this algorithm led to a significant reduction in alkaline phosphatase isoenzyme analysis, without compromising patient care. Total savings could be increased if 25 hydroxyvitamin D was used as a first-line test, for all patients with an elevated alkaline phosphatase and a normal gamma glutamyl transferase regardless of age. This algorithm is cost-effective and can be implemented in laboratories with 25 hydroxyvitamin D assay.

Reference intervals of carbohydrate antigen 19-9 in the apparently healthy adult population.

To establish reference intervals of carbohydrate antigen 19-9(CA 19-9) according to the CLSI CA28-A3 guideline and to evaluate age- and gender-related variations. Serum CA 19-9 values of 10149 healthy subjects (from 20years old to 60years old) were measured from location health checkups. The relationship between CA 19-9 and age was analyzed using Spearman's approach. The reference intervals of CA19-9 were established using Q2.5 and Q97.5 , and the 90% confidence intervals of upper limits were calculated. The reference intervals of CA 19-9 were 1.98-25.12 U/mL for males (1.97-25.06 U/mL for 20-50years old and 2.31-26.13 U/mL for 50-60years old) and 2.36-29.29 U/mL for adult (20-60years old) females. The upper limit of reference intervals for all individuals was 26.45U/mL; the level of CA 19-9 is higher in females than males. Carbohydrate antigen (CA) 19-9 is significantly associated with aging in adult males(r=.0930, P<.0001), but not in females (P=.4734). Establishing reference intervals for CA19-9 and giving age-related reference intervals of CA19-9 using a big data of healthy adult, we first discovered that CA19-9 tends to increase with age in adult males but not in females.

The limit of reference range of TSH: long-term discussion and possibilities of modern diagnostic.

The review considers problem of upper limit of reference interval of TSH that is discussed predominantly by endocrinologists out of laboratory community. The common values of 0.4-4.0 mE/l combine as a matter of fact two ranges: zone of practically full wellbeing (0.4-2.5 mE/l) and zone of latent pathology and/or high possibility of development of clinically significant hypothyroidism (2.5-4.0 mE/l). At one time, the proposal to diminish upper limit of reference interval provoked many discussions and on balance received no approval. However, no unanimity concerning this issue is still to be achieved. The article discusses data forcing medical specialists to be wary of values of TSH in the range of 2.5-4.0 mE/l. At the same time, the question is putted concerning suitability of using population reference intervals in the case of both of TSH and number of other indices of laboratory diagnostic.

Analysis and comparison of reference intervals of complete blood cell count with the published standards

Objective To analyze the status of reference intervals（RIs）of complete blood cell count（CBC）in China and compare them with the published standards. Methods The RIs information of CBC（containing the items of WBC, RBC, Hb, HCT, MCV, MCH, MCHC and PLT）were collected by the External Quality Assessment（EQA）software from laboratories participated in the Second Complete Blood Cell Count EQA Program in 2013, which including the sources of RIs, the lower and upper limits of RIs and the validation information of RIs. The sources and validation information of RIs were analyzed by Microsoft Excel 2007 using all data except those from maternal and child care service center, children′s hospital and corporations. The outliers of limits of RIs were excluded according to the International Federation of Clinical Chemistry（IFCC）guidelines ，then data were analyzed by SPSS 13.0. The mean of the upper and lower limits of the RIs were compared with the published standards by the t-test. Results Totally 299（57.72%）of 518 laboratories reported were using RIs according to National Clinical Laboratory Operation Rules, while 112（26.62%）labs were using RIs from instrument/reagent manufacturer instructions, 411（80.00%）labs did not validate the RIs they used, of which 258（50.00%）did not know how to validate RIs. The deviation of the maximum and the minimum ranged from 16% to 70%. More than one third laboratories did not separate RIs of RBC, Hb and HCT according to the gender. The upper and lower limits of WBC and MCV of most laboratories were higher, while those of RBC(male/female), PLT and Hb(male) were lower than that from the published standard. The RIs of MCH was narrower than that from the published standard. Meanwhile, HCT, MCHC (male/female) and Hb (female) were near the upper and lower limits of published standards. Conclusions At present, the RIs of CBC used in laboratories is chaotic, which is significantly different from the published standard. On the basis of standardization, the RIs of published standard result from a multi-center study in Chinese people should be preferred.（Chin J Lab Med,2014,37:539-543） Key words: Blood cell count; Reference values; Quality control

Femoral head-neck offset measurements in 339 subjects: distribution and implications for femoroacetabular impingement

The α-angle is a frequently used measurement to quantify head-neck offset pathology in cam-type femoroacetabular impingement. However, diverging norm values and reference intervals have been described, especially in men. The α-angle, the head-neck offset ratio and the triangular index were measured on anteroposterior and lateral radiographs of 339 (170 men and 169 women) subjects without evident underlying hip pathology. For male subjects, the mean α-angle was 49.4° (SD 10.5°) on anteroposterior and 49.1° (SD 10.6°) on lateral radiographs, whereas for female subjects, it was 45.0° (SD8.0°) and 46.1° (SD 9.9°), respectively. Thus, calculated upper limits of reference intervals in the population screened were 70° for both radiographic projections in men and 61° (anteroposterior) and 66° (lateral) in women. These data substantiate recent findings that the pathological threshold of the α-angle in male subjects may be lower than that previously assumed. Diagnostic, Level III.

Reference Intervals for Common Laboratory Tests in Melanesian Children

Pediatric reference intervals for biochemical tests are often derived from studies in Western countries and may not be applicable to the developing world. No such intervals exist for Melanesian populations. The aim of this study was to provide specific reference intervals for children from Papua New Guinea (PNG). We assayed plasma from 327 healthy Melanesian children living in Madang Province for common biochemical and hematological analytes. We used well-validated commercially available assay methodology. Compared with reference intervals from children from Western countries and/or African children, there were substantial differences in hemoglobin, soluble transferrin receptor, ferritin, calcium, phosphate, and C-reactive protein. Differences in the upper limits of reference intervals for bilirubin and alanine aminotransferase were also observed. Available reference intervals from Western and African countries may be inappropriate in PNG and other Melanesian countries. This has implications for clinical care and safety monitoring in pharmaceutical intervention trials and vaccine studies.

Value of ischemia-modified albumin in the diagnosis of pulmonary embolism

Background Pulmonary embolism (PE) is a common condition, but the diagnostic strategy for the evaluation of suspected PE is somewhat controversial. Despite the use of various biochemical markers (such as D-dimer and C-reactive protein) and various probability calculation algorithms based on clinical findings for that purpose, there is still a need for more specific and practical markers in PE diagnosis. The aim of this study was to investigate the diagnostic value of ischemia-modified albumin (IMA) levels in the diagnosis of PE. Methods This case-control study was performed in the emergency department between March and September 2006. The serum IMA levels of a total of 60 individuals, consisting of 30 PE patients who had been definitively diagnosed via spiral computed tomographic angiography and 30 healthy volunteers, were examined. Results The measurement of IMA levels in patient plasma yielded mean values of 0.724 ± 0.122 absorbance unit (ABSU) in the PE group and 0.360 ± 0.090 ABSU in the control group. When plasma IMA levels in the PE group were compared with those in the control group, statistically significant increases in IMA were observed in the former ( t = 13.19, df = 56, P < .0005). The value of 0.540 ABSU was calculated as the upper limit of reference interval. In the PE group, 97.7% (n = 29) had values exceeding 0.540 ABSU; none of the control subjects had values exceeding this cutoff value. Conclusions In conclusion, our data suggest that IMA levels may be useful as a discriminative marker to exclude pulmonary embolism.