Adult Reference Range Research Articles

Tenapanor Improves Long-Term Control of Hyperphosphatemia in Patients Receiving Maintenance Dialysis: the NORMALIZE Study.

Most patients with end-stage kidney disease and hyperphosphatemia have difficulty controlling serum phosphate concentrations (sP) despite maintenance dialysis, dietary restriction, and phosphate binder treatment. NORMALIZE evaluated the efficacy and safety of tenapanor 30 mg twice daily alone or in combination with phosphate binders to achieve sP within the adult population reference range (2.5-4.5 mg/dL). Patients who completed the phase 3 PHREEDOM study could enroll in NORMALIZE. Patients enrolled in NORMALIZE who had received tenapanor during the PHREEDOM study (n=111) added sevelamer carbonate if sP was >4.5 mg/dL. Patients who had received sevelamer carbonate during the PHREEDOM study (n=61) added tenapanor and decreased sevelamer carbonate if sP was ≤4.5 mg/dL, per protocol titration schedule. Patients were followed in NORMALIZE for up to 18 months. We assessed efficacy in the full analysis set (FAS), defined as patients who received ≥1 dose of study drug and had ≥1 posttreatment sP measurement (n=171). We assessed safety in all patients who received ≥1 dose of study drug (n=172). At the endpoint visit, 57 of 171 patients (33%) in the FAS achieved sP between 2.5 and 4.5 mg/dL. Eight of 23 patients (35%) who were on tenapanor alone at the endpoint visit achieved sP between 2.5 and 4.5 mg/dL. The mean reduction from PHREEDOM baseline to end of NORMALIZE in sP was 2.0 mg/dL. Serum iFGF23 was significantly reduced; serum iPTH was significantly reduced among patients with iPTH ≥300 pg/mL at PHREEDOM baseline. The most commonly reported treatment-emergent adverse event was diarrhea in 38 of 172 patients (22%), which led to tenapanor discontinuation in 4 patients (2%). Tenapanor alone or in combination with phosphate binders helped adult patients on maintenance dialysis achieve normal sP concentrations. Safety was consistent with previous studies of tenapanor. A Long-Term Study to Evaluate the Ability of Tenapanor Alone or in Combination With Sevelamer to Treat to Goal Serum Phosphorus in Patients With End-Stage Kidney Disease on Dialysis (NORMALIZE), NCT03988920.

A-112 A Consensus Reference Range for Ionized Magnesium

Abstract Objective Ionized magnesium (iMg) is the physiologically active form of the analyte. Despite this, clinical adoption of iMg is infrequent, and there is only one commercially available analyzer that measures iMg. There are now numerous studies that have examined iMg levels in healthy individuals, and this report will summarize their findings and report a consensus reference range. Relevance Although reference ranges may vary based on population and location, among other factors, a baseline reference range is an important starting point to introducing a new test to any laboratory. Methods A literature search was performed using the search term “ionized magnesium”. Papers with reference ranges for healthy individuals measured by ion-selective electrodes were selected and an attempt was made to establish a reference range for adults and children. Results A total of 10 studies were identified, with 422 healthy individuals [1–10]. There were 322 adults and 100 children. Studies looked at venous samples and serum samples. Venous samples were anticoagulated with lithium heparin.Reference ranges for adults and children are shown below: To convert from mg/dL to mmol/L multiply by 0.41. To convert from mg/dL to MEq/L multiply by 1.22. Conclusions Although a large-scale study would be helpful in determining a more precise reference range, there is reasonably good agreement among studies evaluating iMg reference ranges in healthy adults and children. Further work to evaluate differences among different age groups, genders, and ethnic groups would be helpful to clinicians and researchers. There has been a call for updating reference ranges for total magnesium, as there is a wide variation in reported ranges [11].

Identifying elevated plasma free triiodothyronine levels: age-adapted reference intervals for pediatrics.

Elevated free T3 (FT3) is an important feature for the early diagnosis of several diseases among which Grave's disease or Allan-Hernon-Dudley syndrome. However, there is a lack of age-adapted reference intervals for plasma thyroid hormones in children. We conducted a study to define reference values of peripheral FT3 in children using a commonly used automated immunoassay. All thyroid function test (TFT) results from our lab collected during 9 months were extracted anonymously, and reference intervals establishment followed recommendations validated by International Federation of Clinical Chemistry (IFCC). We defined five reference intervals covering the whole pediatric period. Overall, 26.1% of peripheral FT3 measured in children with normal TSH are out of the adult reference range, and 22.2% are upper it leading to misinterpretation. In a 9-month old patient with severe neurodevelopmental disorders, a pathological elevated FT3 has been securely interpreted using the newly established interval. The study highlights the poor relevance of adult intervals in pediatric cares, as it confirms that plasmatic FT3 is higher during the whole pediatric period. This work reports useful age-adapted reference intervals for free T3 in pediatrics using a widely used electrochemiluminescent Immunoassay (ECLIA) kit.

Relationship of Thyroid Function with Metabolic Parameters in Euthyroid Adults

Objective: Thyroid hormones have a significant effect on carbohydrate, lipid metabolism disorders, and insulin resistance (HOMA-IR) development. Vitamin D (25(OH)D) has been shown also can affect not only the musculoskeletal system, but also almost all tissues in the body, including the thyroid in recent years. In the study, we aim of this study is to investigate the relationship between the levels of thyroid-stimulating hormone (TSH) within the reference range and metabolic parameters in adults. Methods: 561 adult outpatients were divided into 2 groups low normal range (0.27-2.5 mIU/mL) and high normal range (2.5-4.2 mIU/mL) according to TSH, and HOMA-IR, 25(OH)D, and lipid levels were compared. Results: A statistically significant positive correlation was found between TSH and HOMA-IR in both the low normal range group (r = 0.123, p = 0.041) and the high normal range group (r = 0.196, p = 0.001). In the high normal range group, the relationship between TSH with vitamin D (r =-0.200, p =0.003), cholesterol (r =0.143, p =0.024), LDL cholesterol (r =0.154, p =0.018), non-HDL cholesterol (r = 0.134, p = 0.035) levels was statistically significant. Conclusion: Our study shows that high normal TSH levels in euthyroid adults are related to higher insulin resistance and lower 25(OH)D levels, and this interaction is a major contributor to dyslipidemia. Thyroid hormones explain the metabolic disorder in the early stages of T2DM. Therefore, we believe that screening TSH levels and determining the optimal TSH target will be beneficial.

Circulating interleukin-38 concentrations in healthy adults.

Interleukin (IL)-38 is the latest discovered member of the interleukin-1 family, which has anti-inflammatory properties similar to IL-36Ra. Several studies compared circulating IL-38 concentrations in healthy and diseased populations to characterize its role in both auto-immune and inflammatory pathologies, with both higher and lower concentrations being associated with certain diseases. However, in order to use IL-38 as a biomarker, a reference range in healthy adults is needed. To establish a reference IL-38 circulating concentration, accessible data from 25 eligible studies with IL-38 concentrations in healthy adults was collected. To validate the values found in literature, we measured IL-38 concentrations by enzyme-linked immunosorbent assay (ELISA) in several cohorts from our own institute. Additionally, the effect of blood collection techniques, freeze thawing cycles, and hemolysis on IL-38 measurements was assessed. To evaluate the importance of the genetic background of individuals as confounding factor of IL-38 synthesis, we used publicly available eQTL databases with matched data on allele frequencies in individuals of different ethnicities. Mean IL-38 concentrations in the various studies were weighted by their corresponding sample size, resulting in a weighted mean, and weighted upper and lower limits were calculated by mean ± 2 SD. Differences of over 10.000-fold were found in the weighted means between studies, which could not be attributed to the blood collection method or assessment of IL-38 in plasma or serum. Although IL-38 concentrations were markedly higher in Chinese then in European population studies, we could not show an association with the genetic background. From our analysis, a reference range for circulating IL-38 in healthy adults could thus not yet be established.

Hyperphosphatemia: A Clue to Diagnosis

Serum phosphate level reference range in adults is 2.5 mg/dL to 4.5 mg/dL and in children is 3 mg/dL to 6 mg/dL. The causes of hyperphosphatemia fall into four categories. These are decreased renal excretion of phosphorus, exogenous phosphorus administration, redistribution of phosphorus, and pseudohyperphosphatemia. We report a 69-year-old gentleman presented with the history of swelling of feet and facial puffiness of 1 month duration. He had renal failure with normal sized kidneys. Serum phosphorus was high. Advanced investigations revealed plasma cell proliferative disorder (clonal bone marrow plasma cells >10%) on bone marrow examination, presence of M band at the junction of beta-2 and gamma region, and elevated serum IgG and serum beta-2 microglobulin. Hyperphosphatemia in multiple myeloma may be true, or pseudohyperphosphatemia. Diligent history, examination, and investigations have yielded the possibility of pseudohyperphosphatemia owing to multiple myeloma in our patient. The interference with the phosphomolybdate ultraviolet assay for serum phosphorus estimation is one of the reasons of pseudohyperphosphatemia in multiple myeloma. The other mechanism of pseudohyperphosphatemia could be the direct binding of paraprotein to phosphorus.

Single-center real-life experience with testosterone treatment in adult men with Prader-Willi syndrome.

Hypogonadism is the most frequent hormonal deficiency in individuals with Prader‐Willi syndrome (PWS). This often necessitates testosterone treatment, but limited data are available to guide testosterone treatment in adult men with PWS. We aimed to evaluate the serum testosterone concentrations and adverse effects of testosterone treatment in individuals with PWS attending a specialist obesity management service. A retrospective audit was undertaken at Austin Health, Melbourne between January 2010 and April 2021. Main outcome measures were testosterone formulation and dose, serum total testosterone concentration, and prevalence of polycythemia and behavioral disturbance. Data were available for eight individuals with median baseline age 19 years (range, 19–42) and BMI 37 kg/m2 (range, 27–71). Six men had obstructive sleep apnea; none were smokers. Baseline testosterone concentration was 1.8 nmol/L (IQR, 1.1–3.3) with hematocrit 0.43. Testosterone formulations were intramuscular testosterone undecanoate (TU) 1000 mg (n = 5), transdermal testosterone gel 50 mg daily (n = 1), and oral TU 80–120 mg daily (n = 2). Median total testosterone concentration was 9.7 nmol/L (IQR, 8.5–14.7). Nine of 25 (36%) hematocrit results in six patients measured >0.50 (range, 0.50–0.56). Intramuscular TU was well tolerated and was the only formulation to achieve serum total testosterone concentrations in the adult male reference range. Worsening behavioral disturbance resulted in treatment discontinuation in one individual. Our experience reinforces the need to regular monitoring of hematocrit in men with PWS treated with testosterone. However, a worsening of behavior problems was uncommon in this series.

Therapeutic drug monitoring in children and adolescents with schizophrenia and other psychotic disorders using risperidone

Risperidone is commonly used to treat different psychiatric disorders worldwide. Knowledge on dose–concentration relationships of risperidone treatment in children and adolescents with schizophrenia or other psychotic disorders is, however, scarce and no age-specific therapeutic ranges have been established yet. Multicenter data of a therapeutic drug monitoring service were analyzed to evaluate the relationship between risperidone dose and serum concentration of the active moiety (risperidone (RIS) plus its main metabolite 9-hydroxyrisperidone (9-OH-RIS)) in children and adolescents with psychotic disorders. Patient characteristics, doses, serum concentrations and therapeutic outcomes were assessed by standardized measures. The study also aimed to evaluate whether the therapeutic reference range for adults (20–60 ng/ml) is applicable for minors. In the 64 patients (aged 11–18 years) included, a positive correlation between daily dose and the active moiety (RISam) concentration was found (rs = 0.49, p = 0.001) with variation in dose explaining 24% (rs2 = 0.240) of the variability in serum concentrations. While the RISam concentration showed no difference, RIS as well 9-OH-RIS concentrations and the parent to metabolite ratio varied significantly in patients with co-medication of a CYP2D6 inhibitor. Patients with extrapyramidal symptoms (EPS) had on average higher RISam concentrations than patients without (p = 0.05). Considering EPS, the upper threshold of the therapeutic range of RISam was determined to be 33 ng/ml. A rough estimation method also indicated a possibly decreased lower limit of the preliminary therapeutic range in minors compared to adults. These preliminary data may contribute to the definition of a therapeutic window in children and adolescents with schizophrenic disorders treated with risperidone. TDM is recommended in this vulnerable population to prevent concentration-related adverse drug reactions.

Collegiate male athletes exhibit conditions of the Male Athlete Triad.

The primary purpose of this study was to determine prevalence of the Male Athlete Triad (MAT) conditions: low energy availability (EA), low bone mineral density (BMD), and low testosterone in male collegiate athletes from different sports. Participants included 44 collegiate male athletes (age, 20.4 ± 0.2 years; body mass index, 25.3 ± 1.3kg/m2) from 7 sports (cross country, soccer, basketball, wrestling, track, golf, and baseball). Resting metabolic rate, 3-day food intake, 7-day exercise energy expenditure, body composition, and reproductive and metabolic hormones were assessed. Of the total participants, 15% had low EA, 0% had low BMD, 28% had low total testosterone (TT), and 80% had low calculated free testosterone (cFT). There were no significant correlations between EA, BMD, TT, and cFT. Insulin and sex hormone binding globulin (SHBG) were below and on the upper end of the reference range for healthy male adults, respectively. Insulin was negatively correlated with total (r = -0.330, p= 0.043) and lumbar spine BMD z-scores (r = -0.413, p= 0.010). Low TT and low cFT were the most prevalent MAT conditions among all athletes. Further research should investigate the relationship between insulin and SHBG and the role of these hormones in the MAT. Novelty: Assessment of energy availability alone is not sufficient to identify physiological disturbances in collegiate male athletes. Low total and/or free testosterone may be present in some collegiate male athletes, regardless of BMD status. Low insulin and high SHBG concentration may portray the presence of conditions of the MAT in male collegiate athletes.

Symmetric dimethylarginine concentrations in healthy neonatal foals and mares.

BackgroundSymmetric dimethylarginine (SDMA) is a renal biomarker correlated with glomerular filtration rate (GFR).ObjectivesDescribe changes in SDMA in clinically healthy foals and their mares during the first month postfoaling.AnimalsConvenience sampling of healthy periparturient Thoroughbred mares and their full‐term foals from a population of client‐owned horses.MethodsSerum and EDTA whole blood samples were collected from mares in their last month of pregnancy and then from mares and foals at approximately <12 hours, 48 hours, 7 days, and 30 days postbirth. Samples were processed at a commercial reference laboratory for CBC and serum biochemistry, including SDMA concentrations.ResultsA total of 125 foals and 104 mares were included. Upper limits for SDMA concentrations in foals were above the adult horse reference interval for the first 20 or more days of life. Median SDMA concentrations decreased from 70 μg/dL (range, 7‐100 μg/dL) to 18 μg/dL (range, 6‐27 μg/dL) during the first 3 to 4 weeks of life. At birth, the SDMA concentration reference range was established as 0 to 100 μg/dL (upper limit of the assay); 0 to 85 μg/dL for 1 to 4 days old, 0 to 36 μg/dL for 5 to 10 days old, and 0 to 24 μg/dL for 20 to 30 days old. The upper reference limits for SDMA concentrations in mares did not differ from the general reference interval for adult horses. No correlation was identified between mare and foal SDMA concentrations (ρ = .06, P = .58).Conclusions and Clinical ImportanceFoal SDMA concentrations remained higher than the upper limit of the adult reference range and foals require a different reference range dependent on age.

Quantitative Videofluoroscopic Analysis of Swallowing Physiology and Function in Individuals With Chronic Obstructive Pulmonary Disease.

PurposeDysphagia is a serious extra pulmonary manifestation of chronic obstructive pulmonary disease (COPD). However, the nature of abnormalities in swallowing physiology in COPD has yet to be clearly established. We explored the frequency of swallowing measures outside the healthy reference range in adults with COPD.MethodParticipants were 28 adults aged 41–79 years (18 men, 20 women) with stable COPD. Disease severity was classified as GOLD (Global Initiative For Chronic Obstructive Lung Disease) Stages 1 (4%), 2 (25%), 3 (53%), and 4 (18%). Participants underwent a videofluoroscopy and swallowed 20% w/v thin barium in, followed by 20% w/v mildly, moderately, and extremely thick barium prepared with a xanthan gum thickener. Blinded duplicate ratings of swallowing safety, efficiency, kinematics, and timing were performed according to the ASPEKT method (Analysis of Swallowing Physiology: Events, Kinematics and Timing). Comparison data for healthy adults aged < 60 years were extracted from an existing data set. Chi-square and Fisher's exact tests compared the frequencies of measures falling < 1 SD/ > 1 SD from mean reference values (or < the first or > the third quartile for skewed parameters).ResultsParticipants with COPD did not display greater frequencies of penetration–aspiration, but they were significantly more likely (p < .05) to display incomplete laryngeal vestibule closure (LVC), longer time-to-LVC, and shorter LVC duration. They also displayed significantly higher frequencies of short upper esophageal sphincter opening, reduced pharyngeal constriction, and pharyngeal residue.ConclusionThis analysis reveals differences in swallowing physiology in patients with stable COPD characterized by impaired safety related to the mechanism, timing, and duration of LVC and by impaired swallowing efficiency with increased pharyngeal residue related to poor pharyngeal constriction.

Comparison of the handheld RETeval ERG system with a routine ERG system in healthy adults and in paediatric patients.

Electroretinograms (ERG) are necessary for the evaluation of retinal function, however testing children is challenging and only performed at a few specialised centres. The handheld RETeval ERG instrument could prove a valuable tool for clinicians in assessing retinal function. This study evaluates this device using an ISCEV approved modified paediatric protocol and compares it to standard methods using a photic stimulator. Cone and rod ERGs were recorded using a standard photic stimulator (Grass) and the RETeval device. Both methods involve using skin electrodes, without mydriasis and under dark and light conditions. Two groups of participants were recruited: 44 healthy adult subjects (mean age = 39 years) and 37 paediatric patients (mean = 5 years). Three of the paediatric patients were not sufficiently compliant to undertake the RETeval recording. Adult ERG reference range data are presented for the RETeval and compared to the standard system. There is lack of absolute agreement in the measurements between the two devices, highlighting the need for device-specific reference data. In the paediatric group there is a high level of diagnostic agreement between both systems (Cohen's Kappa k = 0.80). The relative sensitivity and specificity of the RETeval was 1.0 and 0.91. Qualitative patient and user feedback is discussed. ERGs are similar between the two methodologies. This study demonstrates that the RETeval device is a useful tool for assessing retinal function in children. Importantly, it is quick, relatively easy to use and can potentially reduce the burden and costs of paediatric electrodiagnostic assessments.

Trends of Fecal Calprotectin and Lactoferrin Results for Infants

Abstract Calprotectin and lactoferrin can be measured in stool to test for inflammation in the gastrointestinal tract associated with inflammatory bowel disease (IBD) versus irritable bowel syndrome (IBS). The clinical specificity of these markers decreases in children versus adults because of the broader differential diagnosis for intestinal inflammation in children. Surprisingly, these tests are frequently ordered for infants (age = 0 years). Therefore, we wanted to assess our historical data in order to understand how infant calprotectin and lactoferrin concentrations change over time and review literature for the potential differential diagnosis for intestinal inflammation in infants. Data were analyzed on 19,543 infants/toddlers ages 0 to 2 years who had a stool test result of either the quantitative ELISA calprotectin PhiCal assay (Eurospital) or qualitative ELISA Lactoferrin Chek assay (Techlab). For the quantitative calprotectin test, the averages and medians were graphed over time in infants. And for the qualitative lactoferrin test, the positivity rate was graphed over time in infants. Both were compared to toddlers of ages 1 to 2 years old. The average level of calprotectin in neonates (0-1 months old) was 336 ± 348 μg/g with a median of 192 μg/g. While these values were dramatically above the adult normal reference range of 0 to 50 μg/g, the average level decreased over time to 119 ± 218 μg/g with a median of 39 μg/g for toddlers 2 years old. The presence of elevated lactoferrin was detected in 89% of neonates versus 34% of toddlers age 2 years. These trends demonstrate that both calprotectin and lactoferrin may be elevated early in life for many infants, but rapidly decline with time. Ordering trends show that, for infants/toddlers age 0 to 2 years, fecal calprotectin ordering has grown rapidly, whereas fecal lactoferrin has remained stable. In conclusion, while fecal calprotectin and lactoferrin are widely used markers of pathologic intestinal inflammation in adults, results in infants must be interpreted with great care. An elevated calprotectin or lactoferrin concentration in infant stool may be pathological, perhaps due to necrotizing enterocolitis or food-associated enteropathy, but is also associated with nonpathological reasons such as intestinal exposure to food antigens or commensal bacteria. Literature studies have shown associations of elevated calprotectin or lactoferrin with diet, gestational age at birth, and even mode of delivery. Thus, it is essential that clinicians interpret calprotectin levels or the presence of elevated lactoferrin in the context of the entire clinical picture and understand the lack of specificity of these markers for pathological conditions in infants.

MON-597 Association of Serum TSH with Atrial Fibrillation in the Elderly

INTRODUCTION: Hypothyroidism and atrial fibrillation (Afib) are both common conditions in elderly patients. Levothyroxine, the most common therapy for hypothyroidism, has a narrow therapeutic window and requires monitoring to ensure that thyroid-stimulating hormone (TSH) remains within the reference range. Subclinical hyperthyroidism whether endogenous or induced by over-treatment with levothyroxine, has been associated with higher rates of Afib. Therefore, the American Thyroid Association has proposed that thyroid hormone replacement be adjusted to maintain a higher TSH in the elderly, with a proposed goal of 4-6 mcIU/mL; however, the evidence behind this target is limited. The purpose of our study was to determine whether TSH outside this target, but within the reference range for young adults, is associated with higher rates of AFib in elderly patients treated with levothyroxine. METHODS: This was a retrospective cohort study of patients aged 65 and older who were treated with levothyroxine therapy. Exclusion criteria included: pre-existing diagnosis of AFib; use of amiodarone in the prior year; recent diagnosis of thyroid cancer; history of pituitary disorders. Patients were followed from their first visit in 2010 through the end of 2017 and stratified into four groups based on median TSH value obtained in 2010. This grouping was maintained throughout the course of the study regardless of changes in TSH values in subsequent years. Primary outcome was incidence of AFib. Descriptive and comparative statistics were performed with continuous variables being assessed with one-way ANOVA or Kruskal-Wallis tests, as appropriate. Categorical variables were assessed with the chi-squared test. Rates of AFib between groups were assessed via Poisson regression with control of underlying confounders. RESULTS: Patients (n=11274) were divided into the following groups: TSH <0.5 (n=989), TSH 0.5-2 (n=3827), TSH 2.0-6.0 (n=5574), and TSH >6.0 (n=883). Age and sex distribution between TSH quartiles was fairly matched, although a trend was seen toward older age and male sex with higher TSH values. Incidence of AFib in the entire cohort was 17%. No association was found between TSH quartile and incidence or severity of AFib. Increased risk of AFib was seen with increasing age and with male sex. DISCUSSION: When compared to patients with subclinical hyperthyroidism, no significant difference was found in incidence of AFib in any of the TSH quartiles. Interestingly, patients with subclinical hyperthyroidism did not have a higher rate of AFib. A limitation of the study is that only TSH during one calendar year was used to form cohorts, which does not allow correlation with TSH changes over time. However, it is reassuring that at least in the short term, a TSH outside recommended ranges does not convey an increased risk of AFib in the elderly.

Serum Procollagen Type I N-Terminal Propeptide and Osteocalcin Levels in Korean Children and Adolescents.

PurposeBone markers can be useful for the diagnosis and treatment of skeletal diseases in children and adolescents. Owing to high skeletal growth velocity and rapid bone turnover, children and adolescents have higher bone marker levels than adults. Thus, a valid age- and sex-specific reference should be established for pediatric populations living in similar environments. We aimed to assess the associations of procollagen type I N-terminal propeptide (P1NP) and osteocalcin with age and sex in a group of healthy Korean children and adolescents.Materials and MethodsThe participants (290 boys and 290 girls, age range 0–18 years) were Korean outpatients. Serum P1NP and osteocalcin levels were measured in control materials and patient samples by electrochemiluminescence immunoassay using an automated Cobas e411 analyzer.ResultsSignificant age-dependent variations in bone marker levels were observed in both sexes (p<0.001). The highest P1NP levels were observed during the first year of life; thereafter, levels decreased until puberty. There was no postnatal peak for osteocalcin; however, its levels remained higher than the adult reference range throughout childhood. Significant differences were observed between boys and girls (p<0.05), especially between the ages of 12 and 17 years. Cobas e411 results for P1NP showed satisfactory precision and linearity.ConclusionWe established reference data for P1NP and osteocalcin levels in healthy Korean children and adolescents, as the first and only study of these parameters in pre-adulthood in Korea. Cobas e411-quantified bone markers may be useful for determining bone metabolism indices.

Ultrasound reference values for inferior vena cava diameter and collapsibility index among adult Nigerians

Background: Correct estimation of intravascular volume is crucial in critically ill and traumatized patients. Measurement of the central venous pressure (CVP) is invasive and time consuming. Studies have shown that inferior vena cava diameter (IVCD) correlates with CVP. Sonographic assessment of IVCD and its respirophasic changes (collapsibility index; CI) is a non-invasive, quick and reliable means of estimating CVP and hence, intravascular fluid volume. Data on such studies are scanty among adult Nigerians. Aim: To establish normograms of IVCD and CI for healthy adults in Benin City, Nigeria as well as determine the relationship of IVCD and CI with height, weight, body mass index (BMI), age and gender. Method: Four hundred apparently healthy adult volunteers were prospectively studied by means of ultrasound. Demographic data and BMI were obtained. The IVCD was measured during inspiration, expiration and sniff. The CI was subsequently calculated for each subject. Statistical Package for the Social Sciences (SPSS) version 17.0 was used for data analysis including tests of significance. Probability values less than or equal to 0.05 were considered significant. Results: The mean IVCD in this study was 6.1±2.2mm and 13.0±4.0 mm for inspiration and expiration respectively. The mean CI was 49.7±0.5%. There was no statistically significant correlation between IVCD and CI with height and BMI. Conclusion: This study has determined normal IVCD and CI reference range for healthy Nigerian adults. The CI is independent of height, weight, BMI and gender. Since the CI is not dependent on physical attributes and gender, it may serve as an objective tool for monitoring the fluid status of patient

The Role of Soluble Interleukin-2 Receptor (sIL-2r) in Diagnosis of Adult Hemophagocytic Lymphohistiocytosis (HLH): A Single Center Retrospective Study

Purpose: Serum soluble interleukin-2 receptor (sIL-2r) is considered an important disease marker in hemophagocytic lymphohistiocytosis (HLH). High levels of sIL2r are indicative of T-cell activation, and sIL2r > 2400 U/mL was 93% sensitive and 100% specific for pediatric HLH in the HLH-2004 diagnostic criteria. [1] There are no published data on its performance characteristics in adults and very limited data in children. [2] We conducted a retrospective study to examine the diagnostic sensitivity and specificity of sIL-2r in diagnosing HPS/HLH, to assess how it varies with disease severity, determine its prognostic significance and ability to discriminate between subgroups of HPS/HLH.Methods: Retrospective data was collected on adult patients with at least one sIL-2r level at Vancouver General Hospital in Vancouver, Canada between March 2012 and April 2017. Patients were subdivided into HLH and non-HLH groups. Sensitivity, specificity, prognosis associated with sIL-2r >10,000U/ml, utility as a marker of disease activity and mean sIL-2r between subgroups of HLH were evaluated. Non-HLH patients did not have convincing evidence to suggest HLH and did not receive HLH-specific therapy. Serum sIL-2r levels were enzyme-linked immunosorbent assay (ELISA; Siemens IMMULITE Immunoassay platform, adult reference range 241-846 U/ml).Results: 81 patients were included, 41 with HLH and 40 with an alternate diagnosis (non-HLH). Non-HLH diagnoses included sepsis, histiocyte disorders, multiple transfusions, liver disease, cardiac disease, autoimmune disease/vasculitis, and other inflammatory diseases. The sensitivity of sIL-2r >2400 U/ml was 93% (95% CI 0.79 - 0.98) and specificity 63% (95% CI 0.46 - 0.77). Specificity improved to 93% (95% CI 0.79 - 0.98) with a threshold of sIL-2r >10,000U/ml. Based on ROC curves, sIL2r is a good diagnostic test (AUC of 0.86) with a threshold that optimizes sensitivity and specificity of 2785U/ml and ferritin is a fair test (AUC 0.78) with an optimal threshold of 5775 ug/L. Similar to ferritin, sIL-2r levels correlated with disease activity in seven HLH patients that had multiple sIL-2r levels drawn during their disease course. Within the HLH group, sIL-2r >10,000U/ml was not associated with worse prognosis. Higher sIL-2r levels were seen in malignancy associated HLH (MAHS) as compared to infection associated HLH (IAHS) and macrophage activation syndrome (MAS).Conclusion: sIL-2r >2,400U/ml is a sensitive test for diagnosis of adult HPS/HLH and has utility in monitoring disease activity. At higher levels (sIL-2r >10,000U/ml), this biomarker loses sensitivity but gains specificity in diagnosing HPS/HLH. Higher sIL-2r levels may indicate MAHS when the underlying etiology is unclear. In adults, secondary HPS/HLH is much more common than primary HLH, and all patients in this study were presumed to be secondary. The defining features of secondary HPS/HLH are pathologic immune activation and hypercytokinemia leading to end organ damage. SIL-2r is elevated in numerous conditions associated with T-cell activation and inflammation, such as lymphoma and autoimmune lymphoproliferative syndrome (ALPS), and larger prospective studies of adults with these and other conditions are needed to better define the specificity of increased sIL-2r for HPS/HLH. Since adult secondary HPS/HLH is increasingly diagnosed and treated in many centers, diagnostic criteria for adult secondary HPS/HLH should incorporate markers of hypercytokinemia and immune activation.

Maturation in Serum Thyroid Function Parameters Over Childhood and Puberty: Results of a Longitudinal Study.

Context:Serum thyroid hormone levels differ between children and adults, but have not been studied longitudinally through childhood.Objective:To assess changes in thyroid-stimulating hormone (TSH) and thyroid hormone levels over childhood and their interrelationships.Design:Cohort study.Setting:The Avon Longitudinal Study of Parents and Children, a population-based birth cohort.Participants:A total of 4442 children who had thyroid function measured at age 7, and 1263 children who had thyroid function measured at age 15. Eight hundred eighty-four children had measurements at both ages.Main Outcome Measures:Reference ranges for TSH, free tri-iodothyronine (FT3), free thyroxine (FT4), their longitudinal stability, and interrelationships.Results:Children at age 7 years had a higher FT3 [6.17 pmol/L, standard deviation (SD) 0.62] than children at age 15 (5.83 pmol/L, SD 0.74); P < 0.0001 with 23.2% of children at age 7 having FT3 above the adult reference range. Higher FT3 levels at age 7 in boys (P = 0.0001) and girls (P = 0.04) were associated with attainment of a more advanced pubertal stage at age 13. TSH was positively associated with FT3 at age 7 and age 15 even after adjusting for confounders. In contrast, TSH was negatively associated with FT4.Conclusions:There are substantial changes in TSH and thyroid hormone levels over childhood, in particular for FT3, which appear to relate to pubertal readiness. Our data provide increased insight into the evolution of the pituitary–thyroid axis over childhood and may have implications for determining optimal ranges for thyroid hormone replacement in children.

Genotoxic changes in peripheral lymphocytes after therapeutic exposure to crude coal tar and ultraviolet radiation

Goeckerman therapy is based on combined exposure to UV radiation (UVA, UVB) and crude coal tar (PAHs). Some indicators suggest a genotoxic hazard, however, the level of genotoxic risk of the therapy has not yet been investigated sufficiently. This study aims to assesss the genotoxic risk. The studied group consisted of patients with chronic stable plaque psoriasis treated by Goeckerman therapy (n = 29). Heparin-treated peripheral blood samples were collected one day before the first treatment and immediately after the last procedure. The lymphocytes were isolated from the blood. The level of genotoxicity was evaluated using an alkaline version of the Comet assay which detects DNA single strand breaks (DNA-SSBs), a neutral version of the Comet assay which detects DNA double strand breaks (DNA-DSBs), and using chromosomal aberrations. The level of DNA-SSBs increased insignificantly (median; Q1-Q3): 1.4 (0.4; 0.1-1.4) vs. 2.5 (0.6; 0.3-2.7) %tDNA (P = 0.11) and the level of DNA-DSBs increased significantly: 7.8 (6.5; 3.4-10.5) vs. 20.7 (19.3; 14.2-24.6) % DNA (P < 0.001). The total number of aberrated cells (P < 0.001) and structurally aberrated cells (P < 0.001) increased significantly. The elevated levels of the DNA-DSBs and the chromosomal aberrations in the peripheral lymphocytes indicated a genotoxic hazard. However, the elevated level of the chromosomal abnormalities was below the upper level of the reference range for healthy Czech adults. While, the genotoxic risk appears to be low, Goeckerman treatment represents a further contribution to the lifetime load of genotoxic factors.

Evaluation of point-of-care maternal venous lactate testing in normal pregnancy

Objective: There is little information about whether the established non-pregnant adult venous lactate reference range is appropriate for pregnancy. This prospective observational study examined whether the non-pregnant adult reference range is appropriate during pregnancy.Methods: Women attending for routine prenatal appointments or elective cesarean delivery in a tertiary hospital were recruited. Clinical details were recorded and venous lactate concentration was measured using a point-of-care (POC) device.Results: Of the 246 women, 199 were 6–18 weeks’ gestation and 47 were 36–42 weeks’ gestation. Mean lactate concentration was within the non-pregnant reference range in early and late pregnancy (0.86 SD ± 0.46 mmol/L and 1.15 SD ± 0.40 mmol/L, respectively). The mean time between phlebotomy and result was 6.1 SD ± 1.7 min. There was no correlation between lactate levels and either maternal age or time interval from tourniquet placement to lactate measurement. In women of 6–18 weeks’ gestation positive bivariate relationships were found between lactate and BMI (p = 0.03, r = 0.158), earlier gestational age (p = 0.04, r= −0.145), and smoking (p = 0.01, r = 0.183), but these were not found in late pregnancy.Conclusions: The venous lactate reference range for the non-pregnant adult may be applied in pregnancy. Further studies should examine lactate dynamics in labor and postpartum.