Comparison of reticulocyte hemoglobin equivalent with traditional markers of iron and erythropoiesis in pediatric dialysis

Background

Anemia is a major complication for patients on chronic dialysis. Erythropoietin is effective if iron is available, however unnecessary iron supplementation results in iron overload. Reticulocyte hemoglobin equivalent (Ret-He) may be useful for assessing iron status.

Methods

A national retrospective cohort study including all children on chronic dialysis in New Zealand between 2007 and 2013, pairing Ret-He with demographic information, anemia indices, and markers of iron status.

Results

In 606 observations, we found a modest relationship between Ret-He and transferrin saturation (TSAT) (r?=?0.34, p?<?0.001) and a poor correlation between Ret-He and ferritin (r?=?0.09, p?=?0.04). There was a negative correlation between ferritin and hemoglobin (r?=??0.14, p?=?0.002), a weak positive correlation between TSAT and hemoglobin (r?=?0.12, p?=?0.007), and a modest positive correlation between Ret-He and hemoglobin (r?=?0.22, p?<?0.001). The diagnostic performance of Ret-He to detect absolute iron deficiency (cut-off value 28.9 pg, sensitivity 90 %, specificity 75 %, AUC 0.87) was good.

Conclusions

Ret-He is a more relevant marker of iron status than ferritin and TSAT. This supports prospectively testing Ret-He to distinguish between iron deficiency and suboptimal erythropoietin dosing as competing causes for anemia. Ferritin is an unhelpful biomarker of iron deficiency in this setting.

     

Visceral fat area and cardiometabolic risk: The Kardiovize study

BackgroundVisceral fat is associated with adiposity-based complications. Bioimpedance measurement allows estimation of visceral fat area (VFA) in an easy manner. However, a validated cut-off value for VFA by bioimpedance associated with cardiometabolic risk is lacking in European population.AimTo determine cut-off values of VFA measured via bioimpedance associated with cardiometabolic risk.MethodsRandom cross-sectional Czech population-based sample of 25–64 years old subjects. Receiver Operating Characteristic (ROC) curves were used and the area under the curve (AUC), sensitivity, and specificity were calculated. The Cardiometabolic Disease Staging System (CMDS) was used to classify cardiometabolic risk: Stage 1 – 1 or 2 metabolic syndrome (MetS) components, without impaired fasting glucose (IFG); Stage 2 – MetS or IFG; Stage 3 – MetS with IFG; Stage 4 – type 2 diabetes and/or cardiovascular disease.Results2052 participants (54.5% females, median age 49 years) were included. Median VFA (inter-quartile range) were 82.2 cm² (54.8) in men and 89.8 cm² (55.6) in women. The best VFA cut-offs associated with Stage 1 in men and women were 71 cm² (sensitivity = 0.654; specificity = 0.427) and 83 cm² (sensitivity = 0.705; specificity = 0.556) ; Stage 2: 84 cm² (sensitivity = 0.673; specificity = 0.551) and 98 cm² (sensitivity = 0.702; specificity = 0.628) ; Stage 3: 90 cm² (sensitivity = 0.886; specificity = 0.605) and 109 cm² (sensitivity = 0.755; specificity = 0.704); Stage 4: 91 cm² (sensitivity = 0.625; specificity = 0.611) and 81 cm² (sensitivity = 0.695; specificity = 0.448), respectively.ConclusionA cut-off value of VFA of 71 cm² in men and 83 cm² in women exhibited the earliest stage of cardiometabolic risk, and 90 cm² in men and 109 cm² in women showed the best performance to detect risk.     

High-throughput sequencing of T-cell receptor alpha chain clonal rearrangements at the DNA level in lymphoid malignancies

Rearrangements of T- and B-cell receptor (TCR and BCR) genes are useful markers for clonality assessment as well as for minimal residual disease (MRD) monitoring during the treatment of haematological malignancies. Currently, rearrangements of three out of four TCR and all BCR loci are used for this purpose. The fourth TCR gene, TRA, has not been used so far due to the lack of a method for its rearrangement detection in genomic DNA. Here we propose the first high-throughput sequencing based method for the identification of clonal TRA gene rearrangements at the DNA level. The method is based on target amplification of the rearranged TRA locus using an advanced multiplex polymerase chain reaction system and high-throughput sequencing, and has been tested on DNA samples from peripheral blood of healthy donors. Combinations of all functional V- and J-segments were detected, indicating the high sensitivity of the method. Additionally, we identified clonal TRA rearrangements in 57 out of 112 tested DNA samples of patients with various T-lineage lymphoproliferative disorders. The method fills the existing gap in utilizing the TRA gene for a wide range of studies, including clonality assessment, MRD monitoring and clonal evolution analysis in different lymphoid malignancies.     

Epidemiology of pre-eclampsia and the other hypertensive disorders of pregnancy

Hypertensive disorders of pregnancy include chronic hypertension, gestational hypertension, pre-eclampsia and chronic hypertension with superimposed pre-eclampsia. Pre-eclampsia complicates about 3% of pregnancies, and all hypertensive disorders affect about five to 10% of pregnancies. Secular increases in chronic hypertension, gestational hypertension and pre-eclampsia have occurred as a result of changes in maternal characteristics (such as maternal age and pre-pregnancy weight), whereas declines in eclampsia have followed widespread antenatal care and use of prophylactic treatments (such as magnesium sulphate). Determinants of pre-eclampsia rates include a bewildering array of risk and protective factors, including familial factors, sperm exposure, maternal smoking, pre-existing medical conditions (such as hypertension, diabetes mellitus and anti-phospholipid syndrome), and miscellaneous ones such as plurality, older maternal age and obesity. Hypertensive disorders are associated with higher rates of maternal, fetal and infant mortality, and severe morbidity, especially in cases of severe pre-eclampsia, eclampsia and haemolysis, elevated liver enzymes and low platelets syndrome.     

Changes in the expression of P-cadherin in the normal, cryptorchid and busulphan-treated rat testis

Adhesion between Sertoli cells and germ cells is important for spermatogenesis. Cadherins are Ca(2+)-dependent transmembrane proteins that mediate cell-cell adhesion. The aim of this study was to compare the expression of P-cadherin in unilaterally cryptorchid and busulphan-treated rat testes using immunohistochemistry. The pattern of expression of P-cadherin in the seminiferous epithelium changed with the stage of the seminiferous epithelium. The membranes of round spermatids and membranes and cytoplasm of spermatocytes were strongly positive. Our experiments revealed that busulphan treatment (2 doses - 10 mg/kg of body weight - 21 days apart) and cryptorchism led to destructive changes in the structure of seminiferous tubules, together with the decrease in P-cadherin expression. The expression of P-cadherin disappeared in the spermatids segregated from the epithelium while segregated spermatocytes remained still positive for P-cadherin during the 3- to 11-day cryptorchid period. In busulphan-treated animals, the expression of P-cadherin was dependent on the presence or absence of the spermatocytes and spermatids in the tubules. Strong positivity for P-cadherin was observed in the spermatocytes that re-appeared in the regenerating seminiferous epithelium. We suggest that P-cadherin participates in the architecture of adherens junctions in testis, plays an important role in maintaining normal spermatogenesis and that cryptorchism and busulphan treatment lead to adherens junction disintegration.     

The importance of advanced parental age in the origin of neurofibromatosis type 1

Von Recklinghausen neurofibromatosis (NF1) is an autosomal dominant disorder with a prevalence about 1/3,000 (1/2,000-1/5,000 in various population-based studies). About 30-50% of cases are sporadic, resulting from a new mutation. NF1 is fully penetrant by mid-childhood, stigmata, and medical problems (neurological, dermatological, endocrine, ophthalmological, oncological) are highly variable. Advanced paternal age (APA) has been known to increase the risk of new germline mutations that contribute to the presence of a variety of genetic diseases in the human population. The trend in developed countries has been toward higher parental age due to various reasons. In a cross-sectional study, in two university hospital centers, data on parental age of 103 children (41 female) born between 1976 and 2005 with sporadic NF1 were analyzed. Parental age at birth was compared with the Czech general population matched to birth year. The mean NF1 sporadic case paternal age at birth was 32.0 years (95% CI 30.7-33.3 years) compared with 28.8 years (95% CI 28.6-29.1 years) in the general population (P?相似文献