High-serum phosphate and parathyroid hormone distinctly regulate bone loss and vascular calcification in experimental chronic kidney disease.

BACKGROUND: In chronic kidney disease (CKD), increases in serum phosphate and parathyroid hormone (PTH) aggravate vascular calcification (VC) and bone loss. This study was designed to discriminate high phosphorus (HP) and PTH contribution to VC and bone loss. METHODS: Nephrectomized rats fed a HP diet underwent either sham operation or parathyroidectomy and PTH 1-34 supplementation to normalize serum PTH. RESULTS: In uraemic rats fed a HP diet, parathyroidectomy with serum PTH 1-34 supplementation resulted in (i) reduced aortic calcium (80%) by attenuating osteogenic differentiation (higher α-actin; reduced Runx2 and BMP2) and increasing the Wnt inhibitor Sclerostin, despite a similar degree of hyperphosphataemia, renal damage and serum Klotho; (ii) prevention of bone loss mostly by attenuating bone resorption and increases in Wnt inhibitors; and (iii) a 70% decrease in serum calcitriol levels despite significantly reduced serum Fgf23, calcium and renal 24-hydroxylase, which questions that Fgf23 is the main regulator of renal calcitriol production. Significantly, when vascular smooth muscle cells (VSMCs) were exposed exclusively to high phosphate and calcium, high PTH enhanced while low PTH attenuated calcium deposition through parathyroid hormone 1 receptor (PTH1R) signalling. CONCLUSIONS: In hyperphosphataemic CKD, a defective suppression of high PTH exacerbates HP-mediated osteogenic VSMC differentiation and reduces vascular levels of anti-calcifying sclerostin.

Prevalence of thyroid dysfunction in women in early pregnancy: does it increase with maternal age?

OBJECTIVE: Recent studies report high rates of thyroid disorders in pregnant women. However, the need for universal thyroid screening remains controversial. Our aim was to estimate the prevalence of thyroid dysfunction (TD) during pregnancy and to analyse the association with maternal age. DESIGN AND METHODS: We conducted a cross-sectional study in a referral centre in collaboration with the primary care units from April 2010 to March 2011. The study included 2509 consecutive pregnant women resident in an iodine-sufficient area, mean age 32 years (range 16-47) who were universally screened for TD in their first trimester (median gestation 8 weeks, range 4-13 weeks). Thyroid-stimulating hormone (TSH) and free T4 (FT4) were analysed during the first antenatal visit. We applied first trimester-specific population-based TSH and FT4 reference ranges. RESULTS: We identified 416 women with positive TD screening [16·6%, 95% confidence interval (95% CI) 15·1-18·0]. Of these, 47 had overt hypothyroidism (1·9%), 90 subclinical hypothyroidism (3·6%), 23 overt hyperthyroidism (0·9%), 20 subclinical hyperthyroidism (0·8%) and 236 had isolated hypothyroxinaemia (9·4%). Applying a logistic regression model, age ≥30 years was not associated with a higher risk of TD [odds ratio (OR) 0·85, 95% CI 0·67-1·08] or hypothyroidism (OR 0·72, 95% CI 0·50-1·06). CONCLUSIONS: TD affects one in six pregnant women in an iodine-sufficient population. Maternal age ≥30 years do not increase the risk of TD.

Can vitamin D status be assessed by serum 25OHD in children?

BACKGROUND: To examine the relationship of serum 25-hydroxyvitamin D (25OHD) concentrations with serum parathyroid hormone (PTH) levels, body mass index (BMI), and environmental factors in a population of Caucasian children living at latitude 43°N. METHODS: Cross-sectional study on 288 children aged 1 month to 13 years who presented to a pediatric emergency unit during a 21-month period. RESULTS: Mean (SD) serum 25OHD concentrations were 40.6 (17.6), 30.9 (12.0), and 26.4 (9.9) ng/ml (1 ng/ml = 2.5 nmol/l), in children aged 0-1, 2-5, and ≥ 6 years, respectively. Serum PTH levels were 26.6 (13.6), 24.3 (11.9), and 32.7 (12.1) pg/ml in the same groups. Infants had 25OHD concentrations significantly higher. PTH levels were significantly higher in children aged ≥ 6 years. There was no significant correlation between serum 25OHD and PTH concentrations. Totals of 15.6 % and 2.1 % of children had 25OHD values less than 20 and 10 ng/ml, respectively, but none had elevated serum PTH or clinical manifestations related with vitamin D deficiency. Age (inverse correlation) and season (higher values in summer), but not BMI, sex, and time spent outdoors, influenced serum 25OHD concentrations. CONCLUSIONS: Our results raise doubt on the assumption of only a serum 25OHD threshold as indicative of vitamin D deficiency in children.

Non-thyroidal illness syndrome and its relationship with mortality risk in critically ill children.

Introduction: Non-thyroidal illness syndrome (NTIS) is considered to be associated with adverse outcomes in critically ill children.The hypothesis that thyroid hormones and inflammatory markers are associated with increased prediction of mortality risk scores is tested in this paper. Methods: A prospective observational study was set up in a pediatric intensive care unit (PICU). One hundred and three patients were included. NTIS was defined as a low free triiodothyronine (FT3) value for the patient's age. Thyroid hormones levels and inflammatory markers were determined at admission: FT3, FT4 (free thyroxine), TSH (thyroid-stimulating hormone), rT3 (reverse triiodothyronine), CRP (C-reactive protein) and PCT (Procalcitonin). They were compared between children with a pediatric risk of mortality score PRISM-III >75th percentile (group A, n= 25) and the rest (group B, n = 78). Results: A FT4 value lower than 16.6 pmol/L showed an area under the curve (AUC) of 0.655 (0.56-0.78, p = 0.02), with 76% sensitivity and 61.5% specificity to detect a high risk of mortality. A multiple regression analysis revealed that a FT4 lower than 16.6 pmol/L [OR: 4.92 (1.60-18.19), p = 0.009] and having NTIS [OR: 6.04 (1.45-27.93), p = 0.016] could predict a high risk of mortality. Conclusions: In unselected critically ill children, FT4 and FT3 values at admission could be used as a good predictor of a high mortality risk. We have not achieved a predictive model that combines hormones with inflammatory markers.

Marker of vitamin D status in healthy children: Free or total 25-hydroxyvitamin D?

OBJECTIVE: To assess if serum free 25-hydroxyvitamin D (25OHD) is a better indicator of vitamin D status than total 25OHD in healthy children. METHODS: Cross-sectional prospective clinical study was designed. We measured serum free 25OHD concentrations and its correlation with calculated free 25OHD, total 25OHD, intact parathyroid hormone (PTH), and vitamin D binding protein (DBP) in children. The influence of age, sex, ethnicity, body mass index (BMI), season of the year, diet intake, vitamin supplements, time spent outdoors and albumin concentrations on free 25OHD was also analyzed. 241 children aged from 0 days to 14 years, and living in the northern Spain (latitude 43° N), were included. RESULTS: Mean (SD) free 25OHD concentrations were 2.48 (1.39), 5.46 (3.12), 4.12 (1,72), 3.82 (1.43) pg/ml in children aged 0 days, 1 month-2 years, 2-6 years and >6 years, respectively. Correlation between directly measured and calculated free 25OHD was high and significant (r = 0.66) as well as the correlation between serum free and total 25OHD concentrations (r = 0.61). No significant correlation was found between PTH and free 25OHD (r = -0.08). The total 25OHD and PTH concentrations' correlation was inverse (r = -0.25) and significant. Neither free nor total 25OHD concentrations correlated with DBP concentrations. Among the analyzed variables, free 25OHD values were higher in spring/summer than in autumn/winter in children older than 6 years. CONCLUSIONS: : These findings do not support that free 25OHD is a better marker of vitamin D deficiency than total 25OHD in healthy pediatric population.

Lung strain and biological response in mechanically ventilated patients.

PURPOSE: Lung tissue may exhibit a biochemical response to excessive deformation. Since strain has been proposed as a marker of such deformation, we studied the relationships between strain and matrix remodeling and inflammation markers in mechanically ventilated patients with and without acute lung injury (ALI). METHODS: Twenty-two ventilated patients were studied (16 with ALI, 6 controls). Clinical data, gas exchange and respiratory mechanics were recorded, and end-expiratory lung volume (EELV) was measured by oxygen washin/washout. Extracellular matrix remodeling markers (procollagen, matrix metalloproteinases -2 and -9, TIMP-1) and inflammation markers (IL-6, IL-8, IL-10, IFNγ, IL-17A, and VEGF) were measured in bronchoalveolar lavage fluid (BALF). Strain was computed as the ratio between tidal volume and EELV. Patients with ALI were divided into two subgroups according to the median strain value (0.27). RESULTS: Patients in the ALI group exhibited higher airway pressures, lower EELV and higher strain than the control group. There were no significant differences in gas exchange, respiratory mechanics, or the matrix remodeling markers between ALI patients with normal and high strain. The subgroup of patients with high strain showed a fourfold increase of IL-6 and IL-8 concentrations in BALF, compared with patients with ALI and normal strain or patients without ALI. In the whole sample, IL-6 and IL-8 concentrations in BALF were correlated with strain (Spearman's ρ = 0.67 and 0.77, respectively). CONCLUSIONS: Increased strain is associated with a proinflammatory lung response in patients with ALI.

Clinical utility of NT-proBNP levels in late heart transplantation patients.

BACKGROUND: The present work was aimed to describe NT-proBNP levels in heart transplant patients after the first year postsurgery. METHODS: NT-proBNP concentration was measured in 1231 samples from 142 patients when a routine four-month follow-up was carried out, including other biochemical and clinical examinations. Endomyocardial biopsies were performed only upon clinical suspicion of acute rejection. RESULTS: NT-proBNP concentrations were not significantly correlated to post-transplantation time, though differences were observed according to clinical symptoms (Kruskal-Wallis test, p<0.001). Although multivariate analysis revealed statistically significant association between NT-proBNP concentration and some qualitative (cardiac allograft vasculopathy-CAV-, sex, diabetes) and quantitative (creatinine, hematocrit, age) variables, only moderately relevant contribution was observed for creatinine and CAV. Patients with rejection showed noticeable increases in serum NT-proBNP concentrations, above more than 2.5 times the reference change value (97%). NT-proBNP concentrations higher than 1000ng/L increased in 3.5 times (95%CI: 2.4-5) the risk of death in less than one year. CONCLUSIONS: After the first year from surgery, NT-proBNP concentrations were not associated to post-transplantation time and NT-proBNP could be a useful diagnostic marker for rejection, whenever serial measurements are made. A NT-proBNP cutoff value of 1000ng/L was identified for classifying patients at risk of death after one year.

Umbilical cord blood serum procalcitonin by Time-Resolved Amplified Cryptate Emission (TRACE) technology: reference values of a potential marker of vertically transmitted neonatal sepsis.

BACKGROUND: Neonatal infection remains a major diagnostic problem because of non-specific clinical signs and symptoms, as well as low sensitivity and specificity of routine laboratory tests. C-reactive protein (CRP), white blood cell count, absolute neutrophil count and immature/total neutrophil ratio are the most widely used tests in the diagnosis of sepsis and provide useful information, but none of these has demonstrated to be reliable in detecting all septic infants. Procalcitonin (PCT) has been suggested as a potentially useful laboratory test performed in umbilical cord blood when perinatal bacterial sepsis is under investigation. METHODS: In this study, the reference interval for umbilical cord blood serum PCT was established for the first time by Time-Resolved Amplified Cryptate Emission (TRACE) technology. RESULTS: The reference interval for PCT in umbilical cord blood serum ranged from 0.04 to 0.43 microg/L in 168 non-infected newborn infants (95% CI 0.02-0.06 and 0.35-0.60 microg/L, respectively). Cord blood serum PCT correctly classified one infected patient out of 90 newborn infants at risk of vertically transmitted sepsis and identified another neonate as a potentially infected patient despite having negative blood cultures. However, cord blood CRP misclassified 21 out of the 90 patients as infected neonates. CONCLUSIONS: Cord blood PCT measured by TRACE is a potentially more useful early marker of neonatal sepsis than cord blood CRP.