Impairment of Bone Health in Pediatric Patients with Hemolytic Anemia

Introduction Sickle cell anemia and thalassemia result in impaired bone health in both adults and youths. Children with other types of chronic hemolytic anemia may also display impaired bone health. Study Design To assess bone health in pediatric patients with chronic hemolytic anemia, a cross-sectional study was conducted involving 45 patients with different forms of hemolytic anemia (i.e., 17 homozygous sickle cell disease and 14 hereditary spherocytosis patients). Biochemical, radiographic and anamnestic parameters of bone health were assessed. Results Vitamin D deficiency with 25 OH-vitamin D serum levels below 20 ng/ml was a common finding (80.5%) in this cohort. Bone pain was present in 31% of patients. Analysis of RANKL, osteoprotegerin (OPG) and osteocalcin levels indicated an alteration in bone modeling with significantly elevated RANKL/OPG ratios (control: 0.08+0.07; patients: 0.26+0.2, P = 0.0007). Osteocalcin levels were found to be lower in patients compared with healthy controls (68.5+39.0 ng/ml vs. 118.0+36.6 ng/ml, P = 0.0001). Multiple stepwise regression analysis revealed a significant (P<0.025) influence of LDH (partial r2 = 0.29), diagnosis of hemolytic anemia (partial r2 = 0.05) and age (partial r2 = 0.03) on osteocalcin levels. Patients with homozygous sickle cell anemia were more frequently and more severely affected by impaired bone health than patients with hereditary spherocytosis. Conclusion Bone health is impaired in pediatric patients with hemolytic anemia. In addition to endocrine alterations, an imbalance in the RANKL/OPG system and low levels of osteocalcin may contribute to this impairment

Prevalence of osteopathologies in a single center cohort of survivors of childhood primary brain tumor

BackgroundChildhood primary brain tumors (CPBT) are the second largest group of childhood malignancies and associated with a high risk for endocrine late effects.ObjectiveTo assess endocrine late effects and their relevance for the development of osteopathologies in survivors.MethodsThis single center cross sectional study investigated data from 102 CPBT survivors with a mean age of 13.0 years and a mean age at diagnosis of 8.7 years. Clinical, biochemical, radiographic, and anamnestic data regarding endocrine and bone health were obtained at study visits. In addition, data regarding tumor stage and therapy was obtained by chart review. An expert opinion was applied to define presence of osteopathologies.ResultsImpaired bone health, defined by at least one pathological screening parameter, was present in 65% of patients. 27.5% were found to have overt osteopathologies per expert opinion. 37.8% displayed a severe vitamin D deficiency (25-OH vitamin D &lt; 10 ng/ml) and 11% a secondary hyperparathyroidism. Patients with osteopathologies had lower 25-OH vitamin D levels compared to patients without osteopathologies. Multiple endocrine late effects were present: diabetes insipidus in 10.8%, aberrant pubertal development in 13.7%, central hypocortisolism in 14.9%, thyroid dysfunction in 23.8% and growth hormone deficiency in 21.8%. A total of 31.3% of survivors displayed any endocrinopathy. Tumors located near hypothalamic structures and patients who received irradiation had a higher likelihood of endocrine morbidity.ConclusionThis study indicates that endocrine deficiencies are common in pediatric survivors of CPBTs. Osteopathologies are present in this cohort. A prominent effect of hormonal deficiencies on bone health was not detected, possibly because patients were sufficiently treate for their endocrine conditions or indicating resilience of the childhood bone remodeling process. Vitamin D deficiency is frequent and should be treated as recommended

Does Product Familiarity Matter for Participation? #

Regulation of investor access to financial products is often based on product familiarity indicated by previous use. The underlying premise that lack of familiarity with a product class causes unwarranted participation is difficult to test. This paper uses household-level data from the ‘experiment ’ of German reunification that (exogenously) offered to East Germans access to capitalist products (exogenously) unfamiliar to them. We compare the evolution of post-unification participation of former East and West Germans in financial products, controlling for relevant household characteristics. We vary familiarity differentials by considering (i) both unfamiliar ‘capitalist ’ products (stocks, bonds, and consumer credit) and ones available in the East (savings accounts and life insurance); and (ii) cohorts with different exposure to capitalism. We find that East Germans participated immediately in unfamiliar risky securities, at rates comparable to West Germans of similar characteristics. They phased out disproportionate participation in previously familiar assets as familiarity with capitalist products grew. They were more likely to use consumer debt, partly to catch up with richer new peers. We find no signs of abrupt participation drops that could suggest mistakes or regret related to lack of familiarity

Maternal vitamin D status in preeclampsia: seasonal changes are not influenced by placental gene expression of vitamin D metabolizing enzymes.

Preeclampsia, a hypertensive disorder in pregnancy develops in 2-8% of pregnancies worldwide. Winter season and vitamin D deficiency have been associated with its onset.To investigate the influence of season on maternal vitamin D status and placental vitamin D metabolism.25-OH vitamin D and 1,25-(OH)2 vitamin D were measured in maternal serum obtained during the winter or summer months from 63 pregnant women at delivery (43 healthy, 20 preeclampsia). In a subgroup, mRNA expression of CYP24A1 (24-hydroxylase), CYP27B1 (1α-hydroxylase) and VDR (vitamin D receptor) were quantified by real time PCR in placental samples of 14 women with normal pregnancies and 13 with preeclampsia.In patients with preeclampsia,25-OH vitamin D levels were lower, but differed significantly from controls only in summer (18.21±17.1 vs 49.2±29.2 ng/mL, P<0.001), whereas 1,25-(OH)2 vitamin D levels were significantly lower only in winter (291±217 vs 612.3±455 pmol/mL, P<0.05). A two-factorial analysis of variance produced a statistically significant model (P<0.0001) with an effect of season (P<0.01) and preeclampsia (P = 0.01) on maternal 25-OH vitamin D levels, as well as a significant interaction between the two variables (P = 0.02). Placental gene expression of CYP24A1, CYP27B1, and VDR did not differ between groups or seasons. A negative correlation between placental gene expression of CYP24A1 and CYP27B1 was observed only in healthy controls (r = -0.81, P<0.0001).Patients with preeclampsia displayed lower vitamin D serum levels in response to seasonal changes.The regulation of placental CYP24A1, but not of the VDR or CYP27B1 might be altered in preeclampsia

Assessing key clinical parameters before and after intraventricular hemorrhage in very preterm infants

Intraventricular cerebral hemorrhage (IVH) is one of the most severe complications of premature birth, potentially leading to lifelong disability. The purpose of this paper is the assessment of the evolution of three of the most relevant parameters, before and after IVH: mean arterial pressure (MAP), arterial carbon dioxide pressure (pC

mRNA expression of placental CYP24A1, CYP27B1 and VDR (mean ± SD and (range) do not differ between patients with preeclampsia and healthy controls.

<p>mRNA expression of placental CYP24A1, CYP27B1 and VDR (mean ± SD and (range) do not differ between patients with preeclampsia and healthy controls.</p

Boxplots showing the smallest observation (lower bar), lower and upper quartile (box), median (line in the box) and largest observation (upper bar) of a) maternal 25-OH vitamin D serum levels (ng/mL) in winter (grey box) and summer (open box).

<p>Maternal 25-OH vitamin D levels differ between patients with preeclampsia and healthy controls in the summer (** p<0.01). b) Maternal 1,25-(OH)₂ vitamin D (pmol/mL) serum levels are similar in both groups, but significantly lower during winter months in patients with preeclampsia (** p<0.01).</p

Correlation of placental mRNA expression of CYP24A1 (x-axis) and a) CYP27B1 or b) maternal 25-OH vitamin D (ng/ml) in healthy controls (black circles) and patients with preeclampsia (transparent circles).

<p>a) Placental gene expression of CYP24A1 correlates negatively with CYP27B1 expression in healthy controls (r = −0.81, <i>P</i><0.0001, solid line) but not in the patients with preeclampsia (dotted line). b) CYP24A1 correlates negatively with maternal 25-OH vitamin D levels (r = −0.76, <i>P</i> = 0.01) in patients with preeclampsia (dotted line).</p