Laboratorio de función tiroidea en pediatría. Ventajas y limitaciones de los métodos indirectos para la obtención de intervalos de referencia / Thyroid function laboratory in pediatrics. Advantages and limitations of indirect methods to obtain reference intervals

Obtener intervalos de referencia (IRs) confiables para pruebas de laboratorio en pediatría es particularmente complejo y costoso. Una alternativa a este problema es el uso de métodos indirectos, donde se usan grandes bases de datos preexistentes de pacientes. Nuestros objetivos fueron: calcular IR para TSH y hormonas tiroideas (Perfil tiroideo, PT) en población pediátrica que asiste al Hospital de Pediatría Juan P. Garrahan, por método indirecto y verificar la confiabilidad de los mismos para su aplicación. Se recolectaron datos de 19.842 pacientes entre enero de 2020 y diciembre de 2021. Se aplicaron filtros para eliminar los pacientes que pudieran tener afectado el PT. Los 4.861 pacientes incorporados al análisis fueron divididos en 3 grupos: G1: 0-12 meses (n: 551), G2:13 meses- 7 años (n: 1347) y G3: 8 -18 años (n: 2963). Los IR fueron calculados por 2 métodos: el de Hoffman adaptado y el de CLSI EP28A3, para cada grupo de edad. TSH, TT3 y T4L se analizaron con Architect i4000-Abbott y TT4 con Immulite 2000XPi-Siemens. Para la primera etapa de verificación se utilizaron 20 sueros de pacientes provenientes de análisis prequirúrgicos. Los outliers se detectaron aplicando el método de Tukey. Los datos fueron procesados según CLSI EP28A3c. Los IR obtenidos fueron similares a los previamente publicados obtenidos por método directo. Los resultados de la verificación fueron en su mayoría aceptados. Por lo tanto, los métodos indirectos son una buena alternativa de cálculo de IR en pediatría (AU)

Obtaining reliable reference ranges (RRs) for laboratory tests in pediatrics is particularly complex and costly. An alternative to this problem is to use of indirect methods, where large pre-existing patient databases are used. Our aims were to calculate RRs for TSH and thyroid hormones (thyroid profile, PT) in children seen at Hospital de Pediatría Juan P. Garrahan by indirect methods and to verify their reliability for their application. Data were collected from 19,842 patients seen between January 2020 and December 2021. Filters were applied to eliminate patients in whom the PT was potentially affected. The remaining 4,861 patients included in the analysis were divided into 3 groups: G1: 0-12 months (n: 551), G2: 13 months-7 years (n: 1347) and G3: 8-18 years (n: 2963). RRs were calculated by 2 methods: the adapted Hoffman method and the CLSI EP28A3 method, for each age group. TSH, TT3, and FT4 were analyzed with Architect i4000-Abbott and TT4 with Immulite 2000XPi-Siemens. For the first stage of verification, 20 patient sera from pre-surgical analysis were used. Outliers were detected by applying the Tukey method. The data were processed according to CLSI EP28A3c. The RRs obtained were similar to those previously published using the direct method. The verification results were mostly acceptable. Therefore, indirect methods are a good option for calculating RRs in children (AU)

Revisión del intervalo de referencia del recuento plaquetario: ¿son adecuados los valores que estamos utilizando? / Review of the platelet count reference range: are the values we are using appropriate?

Los intervalos de referencia (IR) dependen de la población y de las características metrológicas del procedimiento de medida utilizado. A pesar de las recomendaciones internacionales, son pocos los laboratorios que establecen sus propios IR para cada magnitud por la dificultad para conseguir voluntarios de referencia y el elevado costo económico asociado. La International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) acepta la adopción de IR bibliográficos o su cálculo por métodos indirectos dado su bajo costo y fácil obtención. Existen varias fuentes confiables de IR bibliográficos para el hemograma. No obstante, para el recuento plaquetario, es una práctica común de los laboratorios emplear el rango de valores de 150-450.109 /L independiente de la metodología utilizada y grupo etario. El objetivo de este trabajo fue revisar los IR bibliográficos disponibles para el recuento plaquetario y estimarlo empleando el método indirecto de Hoffmann a partir de nuestra población. Los métodos indirectos se basan en aplicar criterios de exclusión y cálculos matemáticos sobre los resultados de una base de datos de laboratorio. Nuestros IR para el recuento plaquetario se comparan con los bibliográficos, que han sido establecidos por técnicas de muestreo directo. Por este motivo y dado que no existen estudios poblacionales que lo avalen, sería apropiado reemplazar el rango de 150-450.109 / L. Estos límites podrían seguir empleándose como puntos de corte o niveles de decisión médica para definir, según la clínica y otros resultados de laboratorio, los pacientes que ameritan un seguimiento posterior (AU)

Reference ranges (RR) depend on the population and the metrological characteristics of the measurement procedure used. Despite international recommendations, few laboratories establish their own RRs for each magnitude because of the difficulty in obtaining reference volunteers and the associated high economic cost. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) accepts the use of literaturebased RRs or RRs calculated by indirect methods because of their low cost and easy collection. There are several reliable sources of literature-based RRs for the Cell Blood Count. However, for platelet count, it is common laboratory practice to use the range of 150-450,109 /L regardless of the methodology used and age group. The aim of this study was to review the available literature regarding RRs for platelet count and to establish it using the indirect Hoffmann method in our population. Indirect methods are based on applying exclusion criteria and mathematical calculations on the results of a laboratory database. Our RRs for platelet counts are compared with those in the literature, which have been established by direct sampling techniques. Therefore, and given that there are no population studies to support these findings, it would be appropriate to replace the 150-450,109 /L range. These limits may continue to be used as cut-off points or medical decision levels to define, according to clinical manifestations and other laboratory results, patients who warrant further follow-up (AU)

Impact of high-sensitivity troponin as a selection criterion for healthy people on the reference range of N-terminal pro-B-type natriuretic peptide / 中华检验医学杂志

Objective:The 97.5th percentile upper reference limit (97.5th URL) of N-terminal prob-type natriuretic peptide (NT-proBNP) is influenced by multiple factors and depends on the inclusion criteria of apparently healthy people. In this study, the reference upper limit of NT-proBNP was established on apparently healthy people in Beijing area with abnormal hs-cTn as the exclusion criterion.Methods:According to the latest expert consensus recommendation standards of natriuretic peptide in the detection and clinical application of heart failure published by the Clinical Application Group of Cardiac Bio-Markers of the International Union of Clinical Chemistry, 1 635 healthy people without abnormal appearance of routine indicators such as sex, age, glycated hemoglobin, estimated glomerular filtration rate and medical history were collected. After excluding participants with potential myocardial injury according to hs-cTnI and/or hs-cTnT concentration>99th URL, NT-proBNP 97.5th URL was established in healthy subjects aged 21-40 years ( n=205), 41-50 years ( n=535), 51-60 years ( n=556) and >60 years ( n=339) based on non-parametric statistics. Results:The level of NT-proBNP was positively correlated with age ( r=0.254, P<0.001). The levels of NT-proBNP were positively correlated with hs-cTnI, hs-cTnT in males ( r=0.377 and r=0.429, both P<0.001). The levels of NT-proBNP were also positively correlated with hs-cTnI, hs-cTnT in females ( r=0.132 and r=0.296, both P<0.001). When hs-cTn>99th URL was used as the criterion to exclude patients with potential myocardial injury, among apparently healthy people aged 21-40 years old, 41-50 years old, 51-60 years old and >60 years old, male NT-proBNP 97.5th URL was 81.9 (90% CI 60.0-588.8), 141.2 (90% CI 100.0-263.6), 272.0 (90% CI 193.0-494.0) and 547.9 (90% CI 311.2-738.6), respectively; For females, the rates were 227.5 (90% CI 81.9-360.8), 153.2 (90% CI 128.2-239.5), 300.6 (90% CI 211.0-376.4) and 395.8 (90% CI 242.3-543.5) ng/L, respectively. Conclusions:This study confirmed that hs-cTn>99th URL can be used as an apparent population screening criterion for natriuretic peptide reference interval studies, which is helpful to remove conventional means to include individuals with occult myocardial injury in apparently healthy patients, so as to establish a more rigorous healthy cohort and establishing solid normal NT-proBNP reference interval.

A multi-center analysis of thyroid-stimulating hormone level in apparently healthy elderly population in China / 南方医科大学学报

OBJECTIVE@#To investigate serum thyroid stimulating hormone (TSH) level and its changes with age in apparently healthy Chinese elderly population and analyze the differences between TSH levels detected using Roche and Snibe electrochemiluminescence immunoassay analyzers.@*METHODS@#General clinical data and frozen fasting serum samples were collected from 5451 apparently healthy Chinese elderly individuals (> 60 years) from 10 centers in different geographic regions in China. Thyroid function indexes including TSH level were detected using Roche and Snibe electrochemiluminescence immunoassay analyzer, and the median (2.5% and 97.5% quantiles) TSH level was calculated. The variations of TSH level among the participants with geographic regions, gender, and age (with an interval of 5 years) were analyzed to determine the influence of these factors on TSH level.@*RESULTS@#The reference ranges of serum TSH level established using Roche and Snibe electrochemiluminescence immunoassay analyzers were 0.42-9.47 mU/L and 0.36-7.98 mU/L, respectively, showing significant differences between the two methods (P < 0.001). The TSH levels measured at two centers in Western China were significantly higher than those at the other centers (P < 0.05). In elderly male population, serum TSH level tended to increase with age, which was not observed in elderly female population. At the age of 60-75 years, women generally had higher serum TSH level than men, but this difference was not observed in the population beyond 75 years.@*CONCLUSION@#In elderly population, serum TSH level can vary with geographic region, gender, and age, but there was no need for establishing specific reference ranges for these factors. The differences between different detection methods should be evaluated when interpreting the detection results of TSH level.

Trends and ranges of blood pressure during the first 7 days after birth in extremely premature infants / 中国新生儿科杂志

Objective:To study the trends and ranges of blood pressure in extremely premature infants (EPIs) during the first 7 days after birth.Methods:From January 2016 to December 2020, EPIs born in our hospital were retrospectively analyzed. Their blood pressure were monitored using umbilical arterial catheters and no patients needed anti-hypotension treatment. The clinical data of the infants and their mothers, blood pressure data during the first 7 days after birth, clinical outcomes and complications were collected. The trends of blood pressure in untreated EPIs were analyzed and the blood pressure ranges of EPIs of different gestational ages (GA) were established.Results:A total of 145 cases of EPIs were included and their systolic pressure, diastolic pressure and mean blood pressure showed upward trends during 2~168 h after birth ( P<0.001). The diastolic pressure increased significantly within 24 h after birth ( P<0.05), systolic pressure and mean blood pressure increased significantly within 72 h after birth ( P<0.05). Blood pressure increased with age and GA. Conclusions:The blood pressure of EPIs will increase spontaneously during 7 days after birth. The ranges of blood pressure are measured for infants with different GA to provide clinical evidence for blood pressure management of EPIs during early postnatal period.

Establishment of the normal reference range of neurotransmitters in Han-nationality children aged 3-12 in Hubei province / 中华实用儿科临床杂志

Objective:To establish the normal reference range of neurotransmitters in Han-nationality children aged 3-12 in Hubei province.Methods:A prospective study was conducted on healthy Han-nationality children aged 3-12 who took physical examination in Wuhan Children′s Hospital, Hubei province from January to August 2021.The children were asked for their medical histories, and those with neurological diseases, psychiatric diseases, infection, trauma, and a drug history in the past 2 weeks were excluded.The plasma of 324 children (262 males, 62 females; 217 cases in the 3-7 years old, 107 cases in the 8-12 years old) and urine of 391 children (302 males, 89 females; 266 cases in the 3-7 years old, 125 cases in the 8-12 years old) were collected.They ultra performance liquid chromatography-mass spectrometry multiple techniques (UPLC-MS/MS) were used to detect 10 kinds of neurotransmitters (e.g., dopamine, epinephrine, glutamic acid, etc.) in plasma and 8 kinds of neurotransmitters (e.g., dopamine, epinephrine, 5-hydroxyindoleacetic acid, etc.) in random urine.The normal reference range of neurotransmitters in Han-nationality children aged 3-12 in Hubei province was established.The Kruskal- Wallis H test was made for statistical analysis of the differences in neurotransmitter levels among different age groups and gender groups.The neurotransmitter levels between different groups were compared by the Nemenyi test. Results:There were no significant differences in the levels of various neurotransmitters in children of different genders(all P>0.05). There were significant differences in the levels of dopamine, methoxy-norepinephrine, tryptophan and γ-aminobutyric acid in the plasma of children aged 3-7 years and 8-12 years.There were significant differences in the levels of dopamine, epinephrine, norepinephrine, methoxy-norepinephrine, high vanillic acid and 5-hydroxyindoleacetic acid in the random urine between the 3-7 years old group and the 8-12 years old group. Conclusions:The normal reference range of neurotransmitters in Han-nationality children aged 3-12 in Hubei province is established.This study provides reference for clinical practice and lays a foundation for the study of neurotransmitter-related diseases in children.

Discussion on the reference range and alert level of amisulpride in the treatment of schizophrenia / 四川精神卫生

ObjectiveTo study a therapeutic reference range and laboratory alert level of amisulpride in the clinical treatment of schizophrenia. MethodsPatients who met the diagnostic criteria for schizophrenia in the International Classification of Diseases， tenth edition （ICD-10） were enrolled， and all patients received amisulpride treatment. Data including age， gender， duration of treatment， single daily dose， clinical diagnosis， amisulpride concentration， the scores of the Scale for the Assessment of Positive Symptoms （SAPS）， Scale for the Assessment of Negative Symptoms （SANS） and Positive and Negative Syndrome Scale （PANSS）， the adverse reaction rate and multitherapy were collected. The concentration of amisulpride was compared within different efficacy groups and different dosage groups， meantime， the incidence rate of adverse reactions was compared within different amisulpride concentration groups， and between monotherapy and multitherapy groups. Thereafter， the therapeutic reference range and laboratory alert level of amisulpride in the clinical treatment of schizophrenia were explored via estimating the negative and positive predictive values. ResultsThe amisulpride concentration yielded no statistical difference within different dosage groups and different efficacy groups （F=0.745， 1.343， P>0.05）. The single daily dose among patients in different efficacy groups demonstrated no significant difference （F=0.902， P>0.05）. The correlation between amisulpride treatment efficacy and its concentration denoted no statistical significance （r=0.023， P=0.744）. The clinical efficacy and adverse reaction rate showed no significant difference between monotherapy group and multitherapy group （F=2.198， 0.095， P>0.05）. The concentration of amisulpride was not linearly correlated with the adverse reaction rates ［y=100x/（78.13+x）， r=0.960］. When amisulpride concentrations ranged from 100 to 600 ng/mL， the mean reduction rate was equal to or above 42%， the effective detection rate of the reference cut-off value was equal to or above 1.485， and the incidence of adverse reactions was equal to or below 85%. When amisulpride concentrations ranged from 1400 to 1800 ng/mL， there was a decreasing trend in reduction rate （all<42%） and an increasing trend in adverse reaction rate （all>85%） as the concentration of amisulpride increased. ConclusionA reference range of 100~600 ng/mL and an alert level of 1400 ng/mL are recommended for the clinical safety of amisulpride.

Reference range of serum uric acid and prevalence of hyperuricemia: a cross-sectional study from baseline data of ELSA-Brasil cohort

Abstract Background: Most of the few studies that have established reference ranges for serum uric acid (SUA) have not taken into account factors which may interfere with its levels and followed rigorous laboratory quality standards. The aim of this study was to establish reference ranges for SUA and determine the prevalence of hyperuricemia. Method: Cross-sectional study including 15,100 participants (all sample) aged 35 to 74 years from baseline data of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multicentric cohort of volunteer civil servants from five universities and one research institute located in different regions of Brazil. It was established a reference sample excluding participants with factors that directly influence SUA levels: glomerular filtration rate lower than 60 ml/min, excessive alcohol intake, use of diuretics, aspirin, estrogen or urate-lowering therapy. SUA was measured using the uricase method and following rigorous international quality standards. Reference ranges were defined as values between percentiles 2.5 (P2.5) and 97.5 (P97.5) of SUA distribution in the reference sample, stratified by sex. Hyperuricemia was defined as SUA ≥ 7 mg/100 ml in the all sample. Results: The reference sample was composed of 10,340 individuals (55.3% women, median age 50 years). Reference ranges (P2.5 to P97.5) for SUA were: 4.0 to 9.2 mg/100 ml for men and 2.8 to 6.9 mg/100 ml for women. Sex was a major determinant for SUA levels (median [IQR], mg/100 ml: 6.1 [5.3-7.0] for men versus 4.5 [3.9-5.3] for women, p < 0.001). Higher levels of SUA were found in patients with higher BMI. Higher age had (a modest) influence only for women. The prevalence of hyperuricemia for all sample (N = 15,100) was 31.9% (95% confidence interval [CI] 30.8- 33.0%) in men and 4.8% (95% CI 4.3-5.3%) in women. Conclusion: SUA reference ranges were 4.0 to 9.2 mg/100 ml for men and 2.8 to 6.9 mg/100 ml for women. Prevalence of hyperuricemia was 31.9% in men and 4.8% in women. Updated SUA reference ranges and prevalence of hyperuricemia are higher nowadays and might be used to guide laboratories and the screening for diseases related to SUA.

Discussion on the reference range of thromboelastogram in 916 healthy adults in Shenzhen area / 中国输血杂志

【Objective】 To determine the reference range of thromboelastogram(TEG) and establish a TEG feature for local population by measuring TEG parameters in healthy adults in Shenzhen comparing the difference between gender and age, and analyzing the reference data provided by reagent manufacturer. 【Methods】 A total of 916 healthy adults, aged between 19 to 59, who did their regular health checks in our hospital from September 2020 to August 2021 were selected. The TEG(from Lepu Medical Technology Co., Ltd.) was performed, and the clot reaction time(R), clot formation time(K), coagulation angle(α-Angle), maximum amplitude(MA), coagulation index(CI), fibrinolysis index LY30 and the estimated percent lysis (EPL) were analyzed. 【Results】 The reference ranges of TEG parameters, including R, K, α-Angle, MA, CI, LY30 and EPL, of 916 healthy adults from Shenzhen were 3.25~8.19 min, 0.66~3.18min, 47.70~76.56deg, 50.05~72.91mm, -4.3~3.4, 0~2.2% and 0~3%, respectively. The value of α-Angle, CI, K, LY30, MA and R didn’t all meet the given range provided by the manufacturer; some were exceeding and some inferior to. A total of 227 out of 916 individuals presented abnormal results, relative to the references, in at least one parameter, and 78 were diagnosed of abnormal coagulation based on the given reference range, with a specificity of 75.2%. 【Conclusion】 The reference range of TEG parameters of Shenzhen locals is significantly different from that provided by manufacturers. And it is imperative for local TEG laboratories to establish their own reference ranges according to age and gender groups based on local population characteristics.

Julat Rujukan Bagi Jumlah Homosisteina Dalam Plasma Di Kalangan Kanak-Kanak Di Malaysia (Reference range for plasma total homocysteine among Malaysian’s children) / Jurnal Sains Kesihatan Malaysia

@#Homocystineimia is an Inborn Errors of Metabolism (IEM) which can occur due to accumulation of homocysteine. Homocysteine is one of the sulfur-containing amino acid with thiol group that is formed by demethylation of methionine. Deficiency of enzymes involves in homocysteine metabolism can give rise to seven types of homocystinemia subject to total homocysteine level. Therefore reference ranges are needed to differentiate between normal and abnormal population as well as the type of homocystineimia depending on the enzymes defect in the pathway. Hence, homocysteine reference ranges in children for the Malaysian population were postulated. 3 mL of blood was collected from 86 normal individuals (52 boys and 34 girls) and then subsequently processed and analysed using High Performance Liquid Chromatogrphy – Ion Exchange Chromatography (HPLC-IEC). The calculated mean total homocysteine for the population was 8.1 ± 3.89 µM (95% confidence interval, l 7.3-8.9 µM). Reference range was 2.5 – 16.2 µM with lower and upper cut-off were 1.0 µM dan 21.0 µM, respectively. The newly developed reference range of total homocysteine for Malaysian children is able to reduce false negative cases in the laboratory.

Clinical assessment of acid-base balance in Netherland Dwarf rabbit / Avaliação clínica do equilíbrio ácido-básico em coelhos Anã Holandês

Pet rabbits have increased their popularity in a lot of countries. However, most of the laboratory profiles in rabbit medicine come from the observations made in rabbit as biomodels or meat production. So that further researches are necessary to obtain reference values for hematology and biochemical profiles in pet rabbits and the different breeds, especially, in relation to acid-base balance. The aim of this report was to offer the mean values of the main parameters connected with acid-base profile in Netherland Dwarf breed. Thirty-five healthy rabbits (15 males and 20 females) were studied. Venous blood sample from lateral saphenous vein was analyzed to measure: haematocrit, haemoglobin, blood urea nitrogen, glucose, blood pH, partial pressure of CO2 (pCO2), total CO2, ions bicarbonate, chloride, sodium, potassium, base excess and anion Gap. Results showed a shorter range that those reported by different researchers. Moreover, differences between genders were showed in pCO2, its values were higher in males. It may be associated with a greater cellular metabolism. Values obtained in this research should be taken into account by veterinary clinicians for this breed in their clinical assessments. Besides, these values provide new results in parameters with few reference values.

A popularidade de coelhos como animais de estimação aumentou em muitos países. No entanto, a maioria dos perfis de laboratório em medicina de coelhos advém das observações de biomodelos animais ou da produção de carne. Assim, são necessárias pesquisas adicionais para obter valores de referência para hematologia e perfis bioquímicos em coelhos de estimação, e das diferentes raças, especialmente, em relação ao equilíbrio ácido-base. O objetivo deste relatório foi oferecer os valores médios dos principais parâmetros ligados ao perfil ácido-base na raça Anã Holandês. Trinta e cinco coelhos saudáveis ​​(15 machos e 20 fêmeas) foram estudados. A amostra de sangue venoso da veia safena lateral foi analisada para mensuração: hematócrito, hemoglobina, nitrogênio ureico sanguíneo, glicose, pH sanguíneo, pressão parcial de CO2 (pCO2), CO2 total, íons bicarbonato, cloreto, sódio, potássio, excesso de base e ânion Gap. Os resultados apresentaram um intervalo menor do que aqueles relatados por diferentes pesquisadores. Além disso, as diferenças entre os gêneros foram mostradas na pCO2, seus valores foram maiores no sexo masculino. Pode estar associado a um maior metabolismo celular. Os valores obtidos nesta pesquisa devem ser levados em consideração pelos clínicos veterinários para esta raça em suas avaliações clínicas. Além disso, esses valores fornecem novos resultados em parâmetros com poucos valores de referencia.

Reference values of 25-hydroxyvitamin D revisited: a position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society of Clinical Pathology/Laboratory Medicine (SBPC)

ABSTRACT Hypovitaminosis D is a common condition with a negative impact on health. This statement, prepared by experts from the Brazilian Society of Endocrinology and Metabolism and the Brazilian Society of Clinical Pathology/Laboratory Medicine, includes methodological aspects and limitations of the measurement of 25-hydroxyvitamin D [25(OH)D] for identification of vitamin D status, and identifies individuals at increased risk for deficiency of this vitamin in whom 25(OH)D measurement is recommended. For the general population, 25(OH)D levels between 20 and 60 ng/mL are considered normal, while individuals with levels below 20 ng/mL are considered to be vitamin D deficient. This statement identifies potential benefits of maintaining 25(OH)D levels > 30 ng/mL in specific conditions, including patients aged > 65 years or pregnant, those with recurrent falls, fragility fractures, osteoporosis, secondary hyperparathyroidism, chronic kidney disease, or cancer, and individuals using drugs with the potential to affect the vitamin D metabolism. This statement also calls attention to the risk of vitamin D intoxication, a life-threatening condition that occurs at 25(OH)D levels above 100 ng/mL

Establishment of reference interval for thyroid-stimulating hormone using electrochemiluminescence assay in a healthy adult population from Fortaleza, Brazil

ABSTRACT Objective This study aimed to determine the thyroid-stimulating hormone (TSH) reference interval (RI) and to assess the influence of the use of thyroid ultrasonography (TUS) on reference individual selection from a healthy adult population in Fortaleza, Brazil. Subjects and methods This cross-sectional study recruited patients (N = 272; age = 18-50 years) with normal thyroid function (NTF) and placed them in three groups according to their test results: NTF (n = 272; all participants), TUS (n = 170; participants who underwent thyroid US), RI (n = 124; reference individuals with normal TSH levels). TSH, FT4, TT3, TgAb, and TPOAb concentrations were determined by electrochemiluminescence assay. TUS was performed using a 7-12 MHz multifrequency linear transducer by two radiologists. The 2.5th and 97.5th percentiles of the distribution curve corresponded to lower and upper TSH RI levels, respectively. Results The mean TSH level was 1.74 ± 0.96 mIU/L, and TSH range was 0.56-4.45 mIU/L. There was no difference in the TSH concentrations between men and women nor between the groups. TUS did not appear to be an essential tool for the reference group selection. Conclusion The upper limit of TSH was comparable to the reference interval provided by the assay manufacturer (4.45 vs. 4.20 mIU/L) but the lower limit was not (0.56 vs. 0.27 mIU/L). This finding may have a clinical impact since these values may lead to the misdiagnosis of euthyroid patients with subclinical hyperthyroidism.

Distribution of peripheral blood lymphocyte subpopulations in 654 children of preschool age / 国际儿科学杂志

Objective To investigate the distribution of peripheral blood lymphocyte subpopulations in 654 children aged 28 days to 7 years,and to provide a basis for establishing a normal reference range.Methods A total of 654 healthy Han children aged 28 days to 7 years were enrolled.The children were divided into infant group (28 days-12 months) (180 cases,27.52％),toddler group (1-3 years) (184 cases,28.13 ％),and preschooler group (3-7 years) (290 cases,44.34％).Peripheral blood samples were collected,and the percentages of lymphocyte subpopulation were detected by flow cytometry.Results There were statistically significant differences between boys and girls in CD3+ CD4 + T cells,CD3 + CD8 + T cells percentages and the CD4 +/CD8 + ratio in infant group (Z =-2.595,3.317,-3.492,all P ＜ 0.05);in CD3 +CD4 + T cells percentage in toddler group (Z =2.312,P ＜ 0.05);in CD3 + T cells,CD3 + CD4 + T cells,CD3-CD19 + B cells,CD3-CD16 + CD56 + NK cells percentages and the CD4 +/CD8 + ratio in preschool age group (Z =4.088,4.991,3.129,-6.949,2.141,all P ＜ 0.05).The comparison in all age groups showed significant differences in CD3 + T cells,CD3 + CD4 + T cells,CD3-CD19 + B cells,CD3-CD16 +CD56 + NK cells percentages and the CD4 +/CD8 + ratio in boys (x2 =6.925,51.543,39.563,87.751,30.334,all P ＜ 0.05),in CD3 + CD4 + T cells,CD3 + CD8 + T cells,CD3-CD16 + CD56 + NK cells percentages and the CD4 +/CD8 + ratio in girls (x2 =27.646,44.046,26.066,54.238,all P ＜ 0.05).The CD3 +CD4+ T cells and CD3-CD19+ B cells percentages declined with age (x2 =82.345,40.214,all P ＜0.05);The CD3+ CD8+ T cells and CD3-CD16+ CD56+ NK cells percentages increased with age (x2 =38.43,108.302,all P ＜0.05).Conclusion The peripheral blood lymphocyte subpopulation values differ by gender and age.It is necessary to establish the reference range of lymphocyte subpopulations for children in Lanzhou according to gender and age.

Distribution of peripheral blood lymphocyte subpopulations in 654 children of preschool age / 国际儿科学杂志

Objective@#To investigate the distribution of peripheral blood lymphocyte subpopulations in 654 children aged 28 days to 7 years, and to provide a basis for establishing a normal reference range.@*Methods@#A total of 654 healthy Han children aged 28 days to 7 years were enrolled.The children were divided into infant group(28 days-12 months)(180 cases, 27.52%), toddler group(1-3 years)(184 cases, 28.13%), and preschooler group(3-7 years)(290 cases, 44.34%). Peripheral blood samples were collected, and the percentages of lymphocyte subpopulation were detected by flow cytometry.@*Results@#There were statistically significant differences between boys and girls in CD3+ CD4+ T cells, CD3+ CD8+ T cells percentages and the CD4+ /CD8+ ratio in infant group(Z=-2.595, 3.317, -3.492, all P<0.05); in CD3+ CD4+ T cells percentage in toddler group(Z=2.312, P<0.05); in CD3+ T cells, CD3+ CD4+ T cells, CD3-CD19+ B cells, CD3-CD16+ CD56+ NK cells percentages and the CD4+ /CD8+ ratio in preschool age group(Z=4.088, 4.991, 3.129, -6.949, 2.141, all P<0.05). The comparison in all age groups showed significant differences in CD3+ T cells, CD3+ CD4+ T cells, CD3-CD19+ B cells, CD3-CD16+ CD56+ NK cells percentages and the CD4+ /CD8+ ratio in boys(χ2=6.925, 51.543, 39.563, 87.751, 30.334, all P<0.05), in CD3+ CD4+ T cells, CD3+ CD8+ T cells, CD3-CD16+ CD56+ NK cells percentages and the CD4+ /CD8+ ratio in girls(χ2=27.646, 44.046, 26.066, 54.238, all P<0.05). The CD3+ CD4+ T cells and CD3-CD19+ B cells percentages declined with age(χ2=82.345, 40.214, all P<0.05); The CD3+ CD8+ T cells and CD3-CD16+ CD56+ NK cells percentages increased with age(χ2=38.43, 108.302, all P<0.05).@*Conclusion@#The peripheral blood lymphocyte subpopulation values differ by gender and age.It is necessary to establish the reference range of lymphocyte subpopulations for children in Lanzhou according to gender and age.

FISHing for 1p19q codel in oligodendroglioma

@#Together with isocitrate dehydrogenase (IDH) mutation, co-deletion of 1p19q (1p19q codel) is a prerequisite for diagnosis of oligodendroglioma, making it imperative that histopathology laboratories introduce testing for 1p19q codel. To date there is still no consensus reference range and cut-offs that confirm deletion of 1p or 19q. We embarked on determining our reference range in 11 formalinfixed, paraffin-embedded non-neoplastic brain tissue using fluorescence in situ hybridisation (FISH) with the Vysis 1p36/1q25 and 19q13/19p13 FISH Probe Kit (Abbott Molecular Inc., USA). At same time we attempted to validate our methodology in 13 histologically-confirmed IDH-mutant oligodendrogliomas. For 1p, percentage cells with deletion (range=8-23%; mean±SD = 15.73±5.50%) and target: control (1p36:1q25) ratio (range = 0.89-0.96; mean±SD = 0.92±0.03) in non-neoplastic brain, differed significantly (p<0.000) from oligodendroglioma (percentage cells with deletion: range = 49-100%; mean±SD = 82.46±15.21%; target:control ratio range:0.50-0.76; mean±SD = 0.59±0.08). For 19q, percentage cells with deletion (range = 7-20%; mean±SD = 12.00±3.49%) and target:control (19q13/19p13) ratio (range:0.90-0.97; mean±SD = 0.94±0.02) in non-neoplastic brain also differed significantly from oligodendroglioma (percentage cells with deletion: range = 45-100%; mean±SD = 82.62±18.13%; target:control ratio range:0.50-0.78; mean±SD = 0.59±0.09). Using recommended calculation method, for diagnosis of 1p deletion, percentage of cells showing deletion should be >32-33% and/or target:control ratio <0.83. For 19q, percentage of cells showing deletion should be >22% and target:control ratio <0.88. Using these cut-offs all 13 oligodendroglioma demonstrated 1p19q codel.

Evaluation of immunological parameters in pregnant women: low levels of B and NK cells / Avaliação dos parâmetros imunológicos em mulheres gestantes: baixos níveis de células B e NK

Abstract Objective To describe the immunological and hematological reference intervals of low-risk pregnant women. Methods A cross-sectional retrospective database analysis of a basic and translational study analyzing the hematological evaluation blood counts and immunophenotyping of TCD3 + , TCD4 + , TCD8 + , B, and natural killer (NK) cells of the peripheral blood in 79 low-risk pregnant women and of 30 control women from the state of Pernambuco, Brazil, was performed. Results No significant differences were detected between the hematological profiles of the 2nd and 3rd trimesters. Nevertheless, the median level of B cells decreased significantly in the 2nd (174 x 103 μL; p < 0.002) and 3rd trimesters (160 x 103 μL; p < 0.001), compared with the control group (296 x 103 μL). Similarly, the median level of NK cells was lower in the 2nd (134 x 103 μL; p < 0.0004) and 3rd trimesters (100 x 103 μL, p < 0.0004), compared with the control group (183 x 103 μL). In contrast, relative TCD4+ and TCD8+ levels increased in the 2nd and 3rd trimesters compared with the controls (TCD4 + : 2nd trimester = 59%; p < 0.001; 3rd trimester = 57%; p < 0.01; control = 50%; and TCD8 + : 2nd trimester = 31%; p < 0.001; 3rd trimester = 36%; p < 0.01; control = 24%). Conclusion Low-risk pregnant women have ~ 40% less B and NK cells in the peripheral blood, compared with non-pregnant women. These parameters may improve health assistance for mothers and contribute to define reference values for normal pregnancies.

Resumo Objetivo Descrever o intervalo de referência imunológico e hematológico de gestantes de baixo risco. Métodos Realizou-se uma análise retrospectiva, de um estudo básico e translacional, analisando o perfil hematológico e a imunofenotipagem das células TCD3 + , TCD4 + , TCD8 + , B e natural killer (NK) do sangue periférico de 79 gestantes de baixo risco e de 30 mulheres (controles) do estado de Pernambuco, Brasil. Resultados Não observamos diferenças significativas entre os perfis hematológicos do 2° e 3° trimestres. No entanto, houve redução das células B no 2° (média = 174 x 103 μL; p < 0,002) e no 3° trimestres (160 x 103 μL; p < 0,001), comparado como grupo controle (296 x 103 μL). A mediana das células NK foi menor no 2° (134 x 103 μL; p < 0,0004) e no 3° trimestres (100 x 103 μL; p < 0,0004), comparado com o grupo controle (183 x 103 μL). Porém, o percentual de TCD4+ e de TCD8+ aumentou no 2° e 3° trimestres em relação aos controles (TCD4 + : 2° trimestre = 59%; p < 0,001; 3° trimestre = 57%; p < 0,01; controle = 50%; e TCD8 + : 2° trimestre = 31%; p < 0,001; 3° trimestre = 36%; p < 0,01; controle = 24%). Conclusão Mulheres grávidas de baixo risco têm ~ 40% menos células B e NK no sangue periférico em comparação com mulheres não grávidas. Estes parâmetros podem melhorar a assistência à saúde das mães e contribuir para a definição de valores de referência para gestações normais.

Reference ranges for D-dimer levels in Malaysian women in the three trimesters of pregnancy

@#Introduction: Plasma D-dimer levels rise progressively during pregnancy, so one cannot apply normal reference ranges, or the usual cut-off value (500ng/mL), for the exclusion of venous thromboembolism (VTE), in pregnant women. This study was carried out in pregnant Malaysian women in order to build applicable reference ranges for D-dimer. Materials and Methods: A cross-sectional study was conducted to measure D-dimer in healthy pregnant women, and a non-pregnant control group, using the quantitative HaemosIL D-dimer HS500 assay. Reference ranges were derived using CLSI ‘Robust’ methods, and differences between group medians were tested using the Kruskal-Wallis and Mann-Whitney U tests. Results: Plasma D-dimer levels were measured in 92 pregnant women (distributed across the three trimesters)and 31 control women. The medians (and reference ranges) in ng/mL were: control 265 (<799); first trimester 481 (<1070); second trimester 1073 (357–1748); 3rd trimester 1533 (771–2410). There were significant differences between the D-dimer levels of each group and each of the other groups (P<0.001). Conclusions: Reference ranges for D-dimer in pregnant Malaysian women have been establised by this study. Whether these ranges can be used to determine cut-off levels for the exclusion of VTE at different stages of pregnancy is doubtful, as the levels rise continuously through pregnancy, and some very high outlying values occur in apparently normal near-term pregnancy.

Establishment and application of reference ranges of thyroid function in relation to pregnancy in Hubei / 中华地方病学杂志

Objective This study aims to establish a reference range of thyroid function indicators for women in different periods of pregnancy in Hubei Province.Methods Using the prospective method,1 487 healthy pregnant women who did pregnancy check-up at Wuhan Maternal and Child Healthcare Hospital from March 2017 to May 2018 were asked to complete questionnaires and whose serum samples were examined,aged (29 ± 4) years within the range of 20-41,include 498 in early pregnancy,525 in middle pregnancy,and 464 in late pregnancy.Then their thyroid stimulating hormone (TSH),free triiodothyronine (FT3) and free thyroxine (FT4) levels were determined using chemiluminescence immunoassay method to establish reference ranges of the indexes of thyroid function,reference ranges were in median (M) and percentage (P2.5-P97.5).At the same time,the newly established reference range was compared with the reference range recommended by the American Thyroid Association (ATA) guidelines to evaluate the thyroid function of 10 232 pregnant women in counties (cities,districts) of Hubei Province.Results Reference ranges in early pregnancy,middle pregnancy and late pregnancy were shown as follows,TSH:1.41 (0.19-4.26),1.45 (0.25-4.39),2.04 (0.51-5.10) mU/L;FT3:4.76 (3.78-16.01),4.65 (3.72-5.91),4.22 (3.41-5.33) pmol/L;FT4:63.71(47.40-86.25),58.28 (41.18-82.36),48.95 (33.41-66.82) nmol/L.The thyroid function assessment of pregnant women with the newly established reference range shows that the detection rate of thyroid dysfunction in pregnant women is was 13.58％ (1 390/10 232),which was lower than 37.98％ (3 886/10 232,x2 =102.58,P ＜ 0.05) diagnosed by the ATA guidelines.Conclusions The reference range of women's specific thyroid function indicators in different stages of pregnancy in Hubei Province is established.Compared with the reference range recommended by ATA,it is more suitable for thyroid function monitoring and thyroid disease screening for pregnant women in Hubei Province.

Acetylcholinesterase activity in the brain of wild birds in Korea—2014 to 2016

Acetylcholinesterase (AChE) activity level can be used as a diagnostic marker for anticholinesterase pesticide poisoning. In this study, we aimed to establish a baseline level of normal brain AChE activity in wild birds. AChE activity was measured in the brains of 87dead wild birds (26 species). The level of AChE activity ranged from 6.40 to 15.9 µmol/min/g of brain tissue in normal wild birds. However, the brain tissue AChE activity level in wild birds exposed to organophosphate (OP) pesticide was 48.0%–96.3% of that in the normal birds. These results may serve as reference values to facilitate routine diagnosis and monitoring of OP-poisoned wild birds.