Adult Hematology and Clinical Chemistry Laboratory Reference Ranges in a Zimbabwean Population

BackgroundLaboratory reference ranges used for clinical care and clinical trials in various laboratories in Zimbabwe were derived from textbooks and research studies conducted more than ten years ago. Periodic verification of these ranges is essential to track changes over time. The purpose of this study was to establish hematology and chemistry laboratory reference ranges using more rigorous methods.MethodsA community-based cross-sectional study was carried out in Harare, Chitungwiza, and Mutoko. A multistage sampling technique was used. Samples were transported from the field for analysis at the ISO15189 certified University of Zimbabwe-University of California San Francisco Central Research Laboratory. Hematology and clinical chemistry reference ranges lower and upper reference limits were estimated at the 2.5^th and 97.5^th percentiles respectively.ResultsA total of 769 adults (54% males) aged 18 to 55 years were included in the analysis. Median age was 28 [IQR: 23–35] years. Males had significantly higher red cell counts, hemoglobin, hematocrit, and mean corpuscular hemoglobin compared to females. Females had higher white cell counts, platelets, absolute neutrophil counts, and absolute lymphocyte counts compared to males. There were no gender differences in eosinophils, monocytes, and absolute basophil count. Males had significantly higher levels of urea, sodium, potassium, calcium, creatinine, amylase, total protein, albumin and liver enzymes levels compared to females. Females had higher cholesterol and lipase compared with males. There are notable differences in the white cell counts, neutrophils, cholesterol, and creatinine kinase when compared with the currently used reference ranges.ConclusionData from this study provides new country specific reference ranges which should be immediately adopted for routine clinical care and accurate monitoring of adverse events in research studies.     

Testosterone Trajectories and Reference Ranges in a Large Longitudinal Sample of Male Adolescents

Purpose

Pubertal dynamics plays an important role in physical and psychological development of children and adolescents. We aim to provide reference ranges of plasma testosterone in a large longitudinal sample. Furthermore, we describe a measure of testosterone trajectories during adolescence that can be used in future investigations of development.

Methods

We carried out longitudinal measurements of plasma testosterone in 2,216 samples obtained from 513 males (9 to 17 years of age) from the Avon Longitudinal Study of Parents and Children. We used integration of a model fitted to each participant’s testosterone trajectory to calculate a measure of average exposure to testosterone over adolescence. We pooled these data with corresponding values reported in the literature to provide a reference range of testosterone levels in males between the ages of 6 and 19 years.

Results

The average values of total testosterone in the ALSPAC sample range from 0.82 nmol/L (Standard Deviation [SD]: 0.09) at 9 years of age to 16.5 (SD: 2.65) nmol/L at 17 years of age; these values are congruent with other reports in the literature. The average exposure to testosterone is associated with different features of testosterone trajectories such as Peak Testosterone Change, Age at Peak Testosterone Change, and Testosterone at 17 years of age as well as the timing of the growth spurt during puberty.

Conclusions

The average exposure to testosterone is a useful measure for future investigations using testosterone trajectories to examine pubertal dynamics.     

Valoración de niveles de testosterona mediante diferentes métodos analíticos en varones sanos

Plasma testosterone concentrations are essential for the diagnosis of several causes of hypogonadism, including late-onset hypogonadism. Defining the normal range for testosterone concentrations poses certain difficulties due to the changes that occur with age and the variability of the different analytical methods used.ObjectivesTo study normal ranges of testosterone in healthy young men and to compare the results of distinct analytical methods.Material and methodsWe recruited 20 healthy men with a mean age of 24.5 years (standard deviation (SD): 5.04) and a mean body mass index (BMI) of 23.8% (SD: 3.3). Total testosterone (TT) was measured by immunochemiluminescence (ICLA) and free testosterone (FT) by radioimmunoassay (RIA). Calculated free testosterone (FTc) and bioavailable testosterone (BT) were calculated using Vermeulen's formula. Serum lutropin (LH), follitropin (FSH) and sex hormone binding globulin (SHBG) were measured by immunoradiometric assays (IRMA).ResultsThe mean concentrations were 20 nmol/l (SD: 4.96) for TT, 0.054 nmol/L (SD: 0.01) for FT, 0.3834 nmol/L (SD: 0.09) for FTc and 9.9 nmol/L (SD: 2.8) for BT. There was no correlation between testosterone measured by different methods other than an association between FT and FTc (r=0.662, p<0.003) and between FTc and BT (r=0.979, p<0.0001). An inverse correlation was found between BMI and TT concentrations (r: ?0.52, p<0.017).ConclusionsThe normal range for testosterone in healthy young men should be established in each laboratory based on the analytical method used.     

Reference values and the effect of clinical parameters on thyroid hormone levels during early pregnancy

Objective: Thyroid dysfunction is a common endocrine problem during pregnancy; correct diagnosis and appropriate treatments are essential to avoid adverse pregnancy outcomes. Besides, it is vital to identify and quantify the major risk factors for gestational thyroid dysfunction, including thyroid autoimmunity, human chorionic gonadotropin (HCG) concentration, body mass index (BMI) and parity. The study objective was to establish reference ranges during early pregnancy and to explore the relationship between risk factors and thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyroxine (FT3).Design, patients and measurements: To establish the reference ranges of thyroid hormone during early pregnancy in China and to identify the risk factors for thyroid dysfunction, woman in the first trimester of pregnancy (4–12 weeks gestation) were recruited. After excluding thyroid peroxidase antibody (TPO-Ab) positive and/or thyroglobulin antibody (TG-Ab) positive women, previous thyroid disease, a lack of iodine intake, reference values were calculated by 2.5th to 97.5th percentiles.Results: After exclusion of TPO-Ab and/or TG-Ab positive women, reference values were as follows: TSH, 0.11–3.67 mIU/l; FT3, 3.19–5.91 pmol/l; FT4 10.95–16.79 pmol/l. Higher BMI was associated with lower FT4 concentrations (P=0.005). In multiple regression analysis, TSH was significantly and positively associated with TG (P=0.03). Maternal parity and maternal age may be risk factors for the abnormal thyroidal response to hCG concentrations.Conclusions: Our study defined first trimester-specific reference ranges for serum TSH, FT4, FT3 in a Chinese population, and demonstrated that BMI ≥23kg/m², maternal parity ≥3 and maternal age ≥30 years may increase the risk of thyroid dysfunction.     

Effects and interaction of meteorological factors on hemorrhagic fever with renal syndrome incidence in Huludao City,northeastern China, 2007–2018

BackgroundHemorrhagic fever with renal syndrome (HFRS), a rodent-borne disease, is a severe public health threat. Previous studies have discovered the influence of meteorological factors on HFRS incidence, while few studies have concentrated on the stratified analysis of delayed effects and interaction effects of meteorological factors on HFRS.ObjectiveHuludao City is a representative area in north China that suffers from HFRS with primary transmission by Rattus norvegicus. This study aimed to evaluate the climate factors of lag, interaction, and stratified effects of meteorological factors on HFRS incidence in Huludao City.MethodsOur researchers collected meteorological data and epidemiological data of HFRS cases in Huludao City during 2007–2018. First, a distributed lag nonlinear model (DLNM) for a maximum lag of 16 weeks was developed to assess the respective lag effect of temperature, precipitation, and humidity on HFRS incidence. We then constructed a generalized additive model (GAM) to explore the interaction effect between temperature and the other two meteorological factors on HFRS incidence and the stratified effect of meteorological factors.ResultsDuring the study period, 2751 cases of HFRS were reported in Huludao City. The incidence of HFRS showed a seasonal trend and peak times from February to May. Using the median WAT, median WTP, and median WARH as the reference, the results of DLNM showed that extremely high temperature (97.5^th percentile of WAT) had significant associations with HFRS at lag week 15 (RR = 1.68, 95% CI: 1.04–2.74) and lag week 16 (RR = 2.80, 95% CI: 1.31–5.95). Under the extremely low temperature (2.5^th percentile of WAT), the RRs of HFRS infection were significant at lag week 5 (RR = 1.28, 95% CI: 1.01–1.67) and lag 6 weeks (RR = 1.24, 95% CI: 1.01–1.57). The RRs of relative humidity were statistically significant at lag week 10 (RR = 1.19, 95% CI: 1.00–1.43) and lag week 11 (RR = 1.24, 95% CI: 1.02–1.50) under extremely high relative humidity (97.5^th percentile of WARH); however, no statistically significance was observed under extremely low relative humidity (2.5^th percentile of WARH). The RRs were significantly high when WAT was -10 degrees Celsius (RR = 1.34, 95% CI: 1.02–1.76), -9 degrees Celsius (1.37, 95% CI: 1.04–1.79), and -8 degrees Celsius (RR = 1.34, 95% CI: 1.03–1.75) at lag week 5 and more than 23 degrees Celsius after 15 weeks. Interaction and stratified analyses showed that the risk of HFRS infection reached its highest when both temperature and precipitation were at a high level.ConclusionsOur study indicates that meteorological factors, including temperature and humidity, have delayed effects on the occurrence of HFRS in the study area, and the effect of temperature can be modified by humidity and precipitation. Public health professionals should pay more attention to HFRS control when the weather conditions of high temperature with more substantial precipitation and 15 weeks after the temperature is higher than 23 degrees Celsius.     

Height at Late Adolescence and Incident Diabetes among Young Men

Background

Short stature was suggested as a risk factor for diabetes onset among middle age individuals, but whether this is the case among young adults is unclear. Our goal was to assess the association between height and incident diabetes among young men.

Methods and Findings

Incident diabetes was assessed among 32,055 men with no history of diabetes, from the prospectively followed young adults of the MELANY cohort. Height was measured at two time points; at adolescence (mean age 17.4±0.3 years) and grouped according to the US-CDC percentiles and at young adulthood (mean age 31.0±5.6 years). Cox proportional hazards models were applied. There were 702 new cases of diabetes during a mean follow-up of 6.3±4.3 years. There was a significant increase in the crude diabetes incidence rate with decreasing adolescent height percentile, from 4.23 cases/10⁴ person-years in the <10^th percentile group to 2.44 cases/10⁴ person-years in the 75^th≤ percentile group. These results persisted when clinical and biochemical diabetes risk factors were included in multivariable models. Compared to the 75^th≤ percentile group, height below the 10^th percentile was associated with a hazard ratio (HR) of 1.64 (95%CI 1.09–2.46, p = 0.017) for incident diabetes after adjustment for age, body mass index (BMI), fasting plasma glucose, HDL-cholesterol and triglyceride levels, white blood cells count, socioeconomic status, country of origin, family history of diabetes, sleep quality and physical activity. At age 30 years, each 1-cm decrement in adult height was associated with a 2.5% increase in diabetes adjusted risk (HR 1.025, 95%CI 1.01–1.04, p = 0.001).

Conclusions

Shorter height at late adolescence or young adulthood was associated with an increased risk of incident diabetes among young men, independent of BMI and other diabetes risk factors.     

Analyse de l’algorithme décisionnel basé sur la testostérone totale et recommandé pour le diagnostic de l’hypogonadisme acquis

Introduction

The diagnosis of acquired hypogonadism is still an important issue for laboratory medicine. Hypogonadism is defined as a sustained decrease of total testosterone confirmed by the biochemistry laboratory and total testosterone measurement is proposed as the initial step in the investigation of hypogonadism. If TT is over 12 nmol/l, the probability of hypogonadism is considered low and it is suggested that patients be referred to others methods of investigation. Only a small percentage of men aged 50 and over are treated for hypogonadism. Seventy percent of men investigated for hypogonadism have a TT of over 12 nmol/l and there is an unpredictable increase of SHBG during this period, reducing the bioavailability of circulating testosterone. The hypothalamic-pituitary gonadal axis is modified with age and contributes to hypogonadism. The efficacy of biochemical investigation of hypogonadism needs to be reassessed.

Materials and methods

Total testosterone and LH were measured on the Centaur immunoanalyser (Siemens) and SHBG was analysed on the Immulite 2000 (Siemens). Bioavailable testosterone was calculated using the formula provided by ISSAM.

Results

Using the algorithm based on TT, only 27.9% of men would have been investigated for hypogonadism. Of the 638 patients considered as normal, 325 showed an index of hypothalamic-pituitary gonadal axis stimulation and possible hypogonadism, revealed by an elevated LH. In these patients with TT superior to 12 nmol/l and a LH superior to 7 UI/l, SHBG level was at the upper limit of or over the reference range. No correlation was observed between calculated BT and the abnormal LH level found in these patients. Calculated BT was not considered a good marker of hypogonadism for these patients.

Conclusion

Elevated LH is a biochemical marker of hypogonadism and should be interpreted in the context of stimulation of the hypothalamic-pituitary gonadal axis. Based on our data, an initial step in the investigation of hypogonadism based only on TT does not seem suitable for the identification of all patients who might experience hypogonadism. A complete investigation should be offered to all patients with clinical evidence of hypogonadism whatever their TT level. In patients who might benefit from hormonal treatment, calculated BT should be interpreted with caution. A definition of hypogonadism based on TT does not seem appropriate and a new definition based on bioavailable testosterone and the hypothalamopituitary gonadal axis should be considered.     

A Normative Model of Serum Inhibin B in Young Males

Inhibin B has been identified as a potential marker of Sertoli cell function in males. The aim of this study is to produce a normative model of serum inhibin B in males from birth to seventeen years. We used a well-defined search strategy to identify studies containing data that can contribute to a larger approximation of the healthy population. We combined data from four published studies (n = 709) and derived an internally validated model with high goodness-of-fit and normally distributed residuals. Our results show that inhibin B increases following birth to a post-natal peak of 270 pg/mL (IQR 210–335 pg/mL) and then decreases during childhood followed by a rise at around 8 years, peaking at a mean 305 pg/mL (IQR 240–445 pg/mL) at around age 17. Following this peak there is a slow decline to the standard mature adult normal range of 170 pg/mL (IQR 125–215 pg/mL). This normative model suggests that 35% of the variation in Inhibin B levels in young males is due to age alone, provides an age-specific reference range for inhibin B in the young healthy male population, and will be a powerful tool in evaluating the potential of inhibin B as a marker of Sertoli cell function in pre-pubertal boys.     

Contribution de la testostérone biodisponible aux explorations hormonales pour le diagnostic de l’andropause

The measurement of bioavailable testosterone (BT) is considered to be an essential analytical criterion for the diagnosis of male hypogonadism, but the reported normal values differ from one study to another and no consensus has been reached concerning the cut-off values for the diagnosis of androgen deficiency in aging males. Using the lower values measured in a group of clinically normogonadic men between the ages of 40 and 49 years, we have established our own cut-off values: 8 nmol/L for total testosterone and 3.5 nmol/L for BT. By applying these criteria to a group of 87 men with clinical symptoms of androgen deficiency, androgen deficiency was confirmed by laboratory assays in only 14% of these men based on total testosterone, but in 60% of men based on BT. The inverse correlation between BT and SHBG was confirmed regardless of the total testosterone level. SHBG assay is very useful for the diagnosis of androgen deficiency in a population of older males, but cannot replace direct measurement of BT for an accurate individual diagnosis.     

Age-Related Decrements in Heat Dissipation during Physical Activity Occur as Early as the Age of 40

Older adults typically experience greater levels of thermal strain during physical efforts in the heat compared to young individuals. While this may be related to an age-dependent reduction in whole-body sweating, no study has clearly delineated at what age this occurs. In the present study, we report direct measurements of human heat dissipation during physical activity in the heat in males ranging in age from 20–70 years. Eighty-five males performed four 15-min bouts of cycling separated by 15-min rest periods, in a calorimeter regulated to 35°C and 20% relative humidity. Direct calorimetry was used to measure total heat loss (whole-body evaporative heat loss and dry heat exchange). We also used indirect calorimetry as a continuous measure of metabolic heat production. Body heat storage was calculated as the temporal summation of heat production and total heat loss over the experimental session. Whole-body sweat rate (WBSR) was calculated from measurements of evaporative heat loss. Males were divided into five age categories for the analysis of WBSR and body heat storage: 20–31 years (n = 18), 40–44 years (n = 15), 45–49 years (n = 15), 50–55 years (n = 21) and 56–70 years (n = 16). Relative to young males, WBSR was reduced in males aged 56–70 during each exercise (all P<0.05), in males aged 50–55 during the second (P = 0.031) and third exercises (P = 0.028) and in males aged 45–49 during the final exercise bout (P = 0.046). Although not significantly different, 40–44 years old males also had a lower rate of heat loss compared to younger males. Over the sum of two hours, the change in body heat content was greater in males 40–70 years compared to young males (all P<0.05). Our findings suggest that middle-aged and older adults have impairments in heat dissipation when doing physical activity in the heat, thus possibly increasing their risk of heat-related illness under such conditions.     

Osteoprotegerin and receptor activator of nuclear factor-kappaB ligand (RANKL) in the serum of healthy adults

AIMS: Osteoprotegerin and the receptor activator of the nuclear factor-kappaB ligand (RANKL) are decisive factors for maintaining the balance between bone formation and bone resorption. As new, sensitive ELISAs have been developed recently, reference serum ranges should be established to use these analytes for possible diagnostic purposes. METHODS: Measurements were performed in serum samples of 142 healthy adults (82 women, 60 men) between 20 and 70 years of age (mean age: 46 years) using ELISA kits from Immundiagnostik, Bensheim, Germany. RESULTS: Serum concentrations of osteoprotegerin were age and gender independent and showed a Gaussian distribution, while RANKL concentrations were also age independent but differed between males and females, with a non-Gaussian distribution. For osteoprotegerin a gender-independent upper 97.5 percentile limit of 3.6 pmol/L was calculated while the corresponding limits for RANKL and the ratio of RANKL to osteoprotegerin amounted to 3.29 pmol/L and 2.78 in women and 1.66 pmol/L and 2.18 in men, respectively. CONCLUSIONS: Both osteoprotegerin and RANKL were quantifiable in serum of healthy adults, which means that these compounds can be used as potential diagnostic tools.     

Application of Probabilistic Multiple-Bias Analyses to a Cohort- and a Case-Control Study on the Association between Pandemrix?and Narcolepsy

Background

An increase in narcolepsy cases was observed in Finland and Sweden towards the end of the 2009 H1N1 influenza pandemic. Preliminary observational studies suggested a temporal link with the pandemic influenza vaccine Pandemrix™, leading to a number of additional studies across Europe. Given the public health urgency, these studies used readily available retrospective data from various sources. The potential for bias in such settings was generally acknowledged. Although generally advocated by key opinion leaders and international health authorities, no systematic quantitative assessment of the potential joint impact of biases was undertaken in any of these studies.

Methods

We applied bias-level multiple-bias analyses to two of the published narcolepsy studies: a pediatric cohort study from Finland and a case-control study from France. In particular, we developed Monte Carlo simulation models to evaluate a potential cascade of biases, including confounding by age, by indication and by natural H1N1 infection, selection bias, disease- and exposure misclassification. All bias parameters were evidence-based to the extent possible.

Results

Given the assumptions used for confounding, selection bias and misclassification, the Finnish rate ratio of 13.78 (95% CI: 5.72–28.11) reduced to a median value of 6.06 (2.5^th- 97.5^th percentile: 2.49–15.1) and the French odds ratio of 5.43 (95% CI: 2.6–10.08) to 1.85 (2.5^th—97.5^th percentile: 0.85–4.08).

Conclusion

We illustrate multiple-bias analyses using two studies on the Pandemrix^™-narcolepsy association and advocate their use to better understand the robustness of study findings. Based on our multiple-bias models, the observed Pandemrix^™-narcolepsy association consistently persists in the Finnish study. For the French study, the results of our multiple-bias models were inconclusive.     

Reference Ranges of Cholesterol Sub-Fractions in Random Healthy Adults in Ouagadougou,Burkina Faso

In Burkina Faso, the values that serve as clinical chemistry reference ranges are those provided by European manufacturers’ insert sheets based on reference of the Western population. However, studies conducted so far in some African countries reported significant differences in normal laboratory ranges compared with those of the industrialized world. The aim of this study was to determine reference values of cholesterol fractions in apparently normal adults in Burkina Faso that could be used to better assess the risks related to cardiovascular diseases. Study population was 279 healthy subjects aged from 15 to 50 years including 139 men and 140 women recruited at the Regional Center of Blood Transfusion of Ouagadougou, capital city of Burkina Faso (West Africa). Exclusion criteria based on history and clinical examination were used for defining reference individuals. The dual-step precipitation of HDL cholesterol sub-fractions using dextran sulfate was performed according to the procedure described by Hirano. The medians were calculated and reference values were determined at 2.5^th and 97.5^th percentiles. The median and upper ranges for total cholesterol, LDL cholesterol, total HDL cholesterol and HDL2 cholesterol were observed to be higher in women in comparison to men (p <0.05). These reference ranges were similar to those derived from other African countries but lower than those recorded in France and in USA. This underscores the need for such comprehensible establishment of reference values for limited resources countries. Our study provides the first cholesterol sub-fractions (HDL2 and HDL3) reference ranges for interpretation of laboratory results for cardiovascular risk management in Burkina Faso.     

Six-Minute Walk Test: Reference Values and Prediction Equation in Healthy Boys Aged 5 to12 Years

OBJECTIVE

This study aimed to (1) generate normative data in healthy boys aged 5–12 years for the six-minute walk test (6MWT), an outcome measure currently used in clinical trials in Duchenne muscular dystrophy (DMD), (2) to describe the relation with anthropometric variables and myometry, and (3) to compare our data with published equations.

METHODS

The 6MWT was conducted in 442 boys according to a standardized protocol, as currently used in clinical trials in DMD. Maximal voluntary isometric contractions for knee flexion and extension were recorded with a hand-held myometer.

RESULTS

The 6MWD increased significantly with age, from 478.0±44.1 m at age 5, to 650.0±76.8 m at age 12, with the steepest increase between 5 and 8 years. Age- and height related percentile curves of the 6MWD were developed. Correlations with anthropometric variables were fair to good (age r = 0.60, height r = 0.57, weight r = 0.44). Myometric variables (knee flexors and extensors) showed correlations of 0.46 and 0.50 respectively. When dividing into two age categories (5–8 years, 9–12 years), these magnitudes of correlations only applied to the younger age group. Additionally, predicted values were calculated according to available reference equations (Geiger and Ben Saad), indicating an overestimation by those equations. Finally, the Geiger equation was refitted to our population.

CONCLUSION

The percentile curves according to age and height provide a useful tool in the assessment of ambulatory capacity in boys aged 5 to 12 years. Significant correlations with anthropometric variables and myometry were only found in the 5–8 years age group. The Geiger prediction equation, currently used to assess ambulatory capacity in DMD was refitted to obtain a more accurate prediction model based on a large sample with a homogenous distribution across the age categories 5 to 12 years and applying the methodology as currently used in clinical trials in DMD.     

Normal serum biochemical and hematological values of the Sulawesi macaques

Sulawesi macaque (SM) species are currently of interest to primatologists for genetic and behavioral studies world wide. However, there are no published reference hematological and serum biochemical profile values for several of the seven SM species. Twenty-five clinically healthy, outdoor housed, ketamine sedated Macaca tonkeana and Macaca maurus were serially sampled (two to four times) over a 16-month period (N = 68). Normal ranges were defined to include two standard deviations and 2.5–97.5 percentile. Significant differences in single sample date comparisons (P < 0.05) of species (serum Ca, MCHC), age (BUN, BUN/creatinine, alkaline phosphatase, phosphorus), gender (total protein, RBC, hemoglobin, HCT) and pregnancy (phosphorus and neutrophil count) groups were found. This normative data facilitates clinical evaluation of SM species and allows comparison to other macaque species.     

Age‐related changes in mean corpuscular volumes in patients without anaemia: An analysis of large‐volume data from a single institute

Although the mean corpuscular volume (MCV) has been associated with various diseases, these associations in relation to the age‐related trends in MCV remain unclear. Therefore, we used a dataset with over one million values to identify the relationship between ageing and MCV changes. All laboratory data obtained between November 1998 and November 2019 at Chungbuk National University Hospital were retrospectively collected. After excluding cases with missing values for individual complete blood count parameters, outlier MCV values, and ages less than 1 year and more than 88 years, 977,335 MCV values were obtained from 309,393 patients. Principal component analysis of blood components with ages and analysis of the median value changes for each blood component across decade‐wise age groups were conducted to identify relationships between ageing and changes in blood components. The median values of MCV showed gradual increments with age. The linear relationship for patients aged 1–25 years had a larger slope than that for patients aged 26–88 years. For MCV, the equation for patients aged 1–25 years was 0.40*(age) + 81.24 in females and 0.45*(age) + 79.58 in males. The equation for patients aged 26–90 years was 0.04*(age) + 88.97 in females and 0.06*age + 88.30 in males. Among patients aged >40 years, the MCV value was higher in men than in women. Analysis of a large dataset showed that the MCV gradually increased with age and the linear relationship differed between patients aged 1–25 and 26–88 years.     

Age-Related Reference Intervals of the Main Biochemical and Hematological Parameters in C57BL/6J, 129SV/EV and C3H/HeJ Mouse Strains

Background

Although the mouse is the animal model most widely used to study the pathogenesis and treatment of human diseases, reference values for biochemical parameters are scanty or lacking for the most frequently used strains. We therefore evaluated these parameters in the C57BL/6J, 129SV/EV and C3H/HeJ mice.

Methodology/Principal Findings

We measured by dry chemistry 26 analytes relative to electrolyte balance, lipoprotein metabolism, and muscle/heart, liver, kidney and pancreas functions, and by automated blood counter 5 hematological parameters in 30 animals (15 male and 15 female) of each mouse strain at three age ranges: 1–2 months, 3–8 months and 9–12 months. Whole blood was collected from the retro-orbital sinus. We used quality control procedures to investigate analytical imprecision and inaccuracy. Reference values were calculated by non parametric methods (median and 2.5^th and 97.5^th percentiles). The Mann-Whitney and Kruskal-Wallis tests were used for between-group comparisons. Median levels of GLU, LDH, Chol and BUN were higher, and LPS, AST, ALP and CHE were lower in males than in females (p range: 0.05–0.001). Inter-strain differences were observed for: (1) GLU, t-Bil, K⁺, Ca⁺⁺, PO₄ ⁻ (p<0.05) and for TAG, Chol, AST, Fe⁺⁺ (p<0.001) in 4–8 month-old animals; (2) for CK, Crea, Mg⁺⁺, Na⁺⁺, K⁺, Cl⁻ (p<0.05) and BUN (p<0.001) in 2- and in 10–12 month-old mice; and (3) for WBC, RBC, HGB, HCT and PLT (p<0.05) during the 1 year life span.

Conclusion/Significance

Our results indicate that metabolic variations in C57BL/6J, 129SV/EV and C3H/HeJ mice after therapeutic intervention should be evaluated against gender- and age-dependent reference intervals.     

Factors Associated with Mortality and Graft Failure in Liver Transplants: A Hierarchical Approach

Background

Liver transplantation has received increased attention in the medical field since the 1980s following the introduction of new immunosuppressants and improved surgical techniques. Currently, transplantation is the treatment of choice for patients with end-stage liver disease, and it has been expanded for other indications. Liver transplantation outcomes depend on donor factors, operating conditions, and the disease stage of the recipient. A retrospective cohort was studied to identify mortality and graft failure rates and their associated factors. All adult liver transplants performed in the state of São Paulo, Brazil, between 2006 and 2012 were studied.

Methods and Findings

A hierarchical Poisson multiple regression model was used to analyze factors related to mortality and graft failure in liver transplants. A total of 2,666 patients, 18 years or older, (1,482 males; 1,184 females) were investigated. Outcome variables included mortality and graft failure rates, which were grouped into a single binary variable called negative outcome rate. Additionally, donor clinical, laboratory, intensive care, and organ characteristics and recipient clinical data were analyzed. The mortality rate was 16.2 per 100 person-years (py) (95% CI: 15.1–17.3), and the graft failure rate was 1.8 per 100 py (95% CI: 1.5–2.2). Thus, the negative outcome rate was 18.0 per 100 py (95% CI: 16.9–19.2). The best risk model demonstrated that recipient creatinine ≥ 2.11 mg/dl [RR = 1.80 (95% CI: 1.56–2.08)], total bilirubin ≥ 2.11 mg/dl [RR = 1.48 (95% CI: 1.27–1.72)], Na⁺ ≥ 141.01 mg/dl [RR = 1.70 (95% CI: 1.47–1.97)], RNI ≥ 2.71 [RR = 1.64 (95% CI: 1.41–1.90)], body surface ≥ 1.98 [RR = 0.81 (95% CI: 0.68–0.97)] and donor age ≥ 54 years [RR = 1.28 (95% CI: 1.11–1.48)], male gender [RR = 1.19(95% CI: 1.03–1.37)], dobutamine use [RR = 0.54 (95% CI: 0.36–0.82)] and intubation ≥ 6 days [RR = 1.16 (95% CI: 1.10–1.34)] affected the negative outcome rate.

Conclusions

The current study confirms that both donor and recipient characteristics must be considered in post-transplant outcomes and prognostic scores. Our data demonstrated that recipient characteristics have a greater impact on post-transplant outcomes than donor characteristics. This new concept makes liver transplant teams to rethink about the limits in a MELD allocation system, with many teams competing with each other. The results suggest that although we have some concerns about the donors features, the recipient factors were heaviest predictors for bad outcomes.     

Comparison of CT-Determined Pulmonary Artery Diameter,Aortic Diameter,and Their Ratio in Healthy and Diverse Clinical Conditions

BackgroundThe main pulmonary artery diameter (mPA), aortic diameter (Ao), and the mPA/Ao ratio, easily measured using chest computed tomography (CT), provide information that enables the diagnosis and evaluation of cardiopulmonary diseases. Here, we used CT to determine the sex- and age-specific distribution of normal reference values for mPA, Ao, and mPA/Ao ratio in an adult Korean population.MethodsData from non-contrast, ECG-gated, coronary-calcium-scoring CT images of 2,547 individuals who visited the Health Screening Center of the Severance Hospital were analyzed. Healthy individuals (n = 813) included those who do not have hypertension, diabetes, asthma, obstructive lung disease, ischemic heart disease, stroke, smoking, obesity, and abnormal CT findings. Both mPA and Ao were measured at the level of bifurcation of the main pulmonary artery.ResultsThe mean mPA and Ao were 25.9 mm and 30.0 mm in healthy participants, respectively, while the mean mPA/Ao ratio was 0.87. Medical conditions associated with a larger mPA were male, obesity, smoking history, hypertension, and diabetes. A larger mPA/Ao ratio was associated with female, the obese, non-smoker, normotensive, and normal serum level of lipids, while a smaller mPA/Ao ratio was associated with older age. In healthy individuals, the 90th percentile sex-specific mPA, Ao, and mPA/Ao ratio were, 31.3 mm (95% CI 29.9–32.2), 36.8 mm (95% CI 35.7–37.5), and 1.05 (95% CI 0.99–1.07) in males, and 29.6 mm (95% CI 29.1–30.2), 34.5 mm (95% CI 34.1–34.9), and 1.03 (95% CI 1.02–1.06) in females, respectively.ConclusionIn the Korean population, the mean mPA reference values in male and female were 26.5 mm and 25.8 mm, respectively, while the mean mPA/Ao ratio was 0.87. These values were influenced by a variety of underlying medical conditions.     

The Vitamin D Status in Inflammatory Bowel Disease

Context

There is no consensus on the vitamin D status of children and adolescents with inflammatory bowel disease (IBD).

Aim

To determine the vitamin D status of patients with IBD by comparing their serum 25(OH)D concentration to that of healthy controls.

Hypothesis

Serum 25(OH)D concentration will be lower in patients with IBD compared to controls.

Subjects and Methods

A case-controlled retrospective study of subjects with IBD (n = 58) of 2–20 years (male n = 31, age 16.38±2.21 years; female n = 27, age16.56±2.08 years) and healthy controls (n = 116; male n = 49, age 13.90±4.59 years; female n = 67, age 15.04±4.12years). Study subject inclusion criteria: diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC). Vitamin D deficiency was defined as 25(OH)D of (<20 ng/mL) (<50 nmol/L), overweight as BMI of ≥85^th but <95^th percentile, and obesity as BMI ≥95^th percentile. Data were expressed as mean ± SD.

Results

Patients with CD, UC, and their controls had mean serum 25(OH)D concentrations of 61.69±24.43 nmol/L, 53.26±25.51, and 65.32±27.97 respectively (ANOVA, p = 0.196). The overweight/obese controls had significantly lower 25(OH)D concentration compared to the normal-weight controls (p = 0.031); whereas 25(OH)D concentration was similar between the normal-weight and overweight/obese IBD patients (p = 0.883). There was no difference in 25(OH)D between patients with UC and CD, or between subjects with active IBD and controls. However, IBD subjects with elevated ESR had significantly lower 25(OH)D than IBD subjects with normal ESR (p = 0.025), as well as controls (65.3±28.0 nmol/L vs. 49.5±25.23, p = 0.045).

Conclusion

There is no difference in mean serum 25(OH)D concentration between children and adolescents with IBD and controls. However, IBD subjects with elevated ESR have significantly lower 25(OH)D than controls. Therefore, IBD subjects with elevated ESR should be monitored for vitamin D deficiency.