A cross-sectional study of growth,nutritional status and body proportions in children and adolescents at a medical center specializing in the treatment of cystic fibrosis in Poland

Introduction

Malnutrition, delayed growth and delayed puberty are commonly seen in children with cystic fibrosis. The aim of this study was to evaluate growth, nutritional status and body proportions in children and adolescents suffering from cystic fibrosis.

Material and methods

The evaluation was based on 19 somatic measurements and indices calculated from these measurements. Somatic development was evaluated in relation to several factors connected to the clinical picture or the course of the disease. Anthropometric data were extracted from the medical histories of 41 boys and 48 girls diagnosed and treated at the Institute of Mother and Child in Warsaw (Poland). Mean values for somatic parameters and body build indices for the children suffering from CF were compared to those for the reference group.

Results

The results revealed that growth in these children was significantly delayed in comparison to that seen in the healthy population (Z-score = –0.56, p < 0.001). Nutritional status was also adversely affected (Z-score = –0.85, p < 0.001). The children suffered more from a deficit in muscularity than in adiposity (Z-score = –0.75 and Z-score = –0.34, p < 0.01, respectively). This was especially true for boys. The children had infantile body proportions and defects in trunk and chest structure.

Conclusions

The factors that most affected somatic development were infection by Pseudomonas aeruginosa and the time at which the disease was diagnosed. Chronic infection by P. aeruginosa and type of CFTR mutation were the factors that most affected pulmonary function parameters.     

The Complement Cascade and Renal Disease

Serum complement cascade, a part of innate immunity required for host protection against invading pathogens, is also a mediator of various forms of disease and injury. It is activated by classical, lectin, and alternative pathways that lead to activation of C3 component by C3 convertases, release of C3b opsonin, C5 conversion and eventually membrane attack complex formation. The tightly regulated activation process yields also C3a and C5a anaphylatoxins, which target a broad spectrum of immune and non-immune cells. The review discusses the involvement of the complement cascade in kidney disease pathogenesis and injury. The role of the complement pathways in autoantibody-mediated forms of glomerulonephritis (lupus nephritis, anti-glomerular basement membrane disease, anti-neutrophil cytoplasmic autoantibody-induced or membranoproliferative glomerulonephritis, membranous nephropathy), C3 glomerulopathy, atypical forms of hemolytic uremic syndrome, ischemic-reperfusion injury of transplanted kidney, and antibody-mediated renal allograft rejection are discussed. The disturbances in complement activation and regulation with underlying genetics are presented and related to observed pathology. Also promising strategies targeting the complement system in complement-related disorders are mentioned.     

Tumor location determines midkine level and its association with the disease progression in colorectal cancer patients: a pilot study

Purpose

The purpose of this study was to evaluate midkine, multipotential cytokine, and growth factor in colorectal cancer (CRC) stratified by tumor location.

Methods

Midkine was assessed immunoenzymatically in paired cancerous and noncancerous tissues from 53 CRCs and referred to CRC stage, tumor location, and size, and circulating cytokine levels.

Results

Midkine was higher in cancerous versus noncancerous tissue in 98?% cases (424.2 vs. 31.1?pg/mg, p?p?=?0.005) due to higher midkine level in noncancerous rectal than colonic tissue (45.5 vs. 26.2?pg/mg, p?=?0.074). Tumor location affected midkine association with CRC stage. Midkine fold change was higher in advanced stages of rectal cancers (16.8 vs. 5.3, respectively in III/IV vs. I/II, p?=?0.013), while it tended to be lower in colonic ones (25.3 vs. 47.8, p?=?0.134). In addition, fold change in midkine level was higher in rectal N1 than N0 cancers (17.3 vs. 16.5, p?=?0.032), while it tended to be lower in colonic cancers (23.6 vs. 50.1, p?=?0.085). Midkine negatively correlated with tumor size (r?=?0.40, p?=?0.017), while it tended to positively correlate with its serum levels (r?=?0.45, p?=?0.081).

Conclusions

Midkine is differently expressed in tumors arising from colonic and rectal mucosa, where it may play diverse roles in carcinogenesis. High midkine expression in noncancerous rectal mucosa might contribute to, a characteristic for rectal cancers, higher incidence of local recurrence. Divergent expression of midkine and its association pattern ought to be taken into account while designing midkine-directed therapies for CRC.     

FGF23 contributes to insulin sensitivity in obese adolescents - preliminary results

Fibroblast growth factor‐23 (FGF23) is a hormonal regulator of circulating phosphate and vitamin D levels. Recent investigations revealed that besides a key role in the pathogenesis of calcium–phosphorus disorders, in some patients FGF23 may be an indicator of cardiovascular complications. As a ‘hormone‐like’ factor, it may also be involved in some metabolic processes, especially in the metabolism of glucose and fat. Its potential contribution to metabolic syndrome (MS) development has not been confirmed yet. Objective The study was to examine the possible correlations between FGF23 serum levels and body composition, blood pressure and selected parameters of glucose, insulin and fat metabolism in adolescents with simple obesity. Patients and design In 68 (35 female) adolescents (mean age 13·9 years) with simple obesity [mean BMI SDS 4·9 (95% CI 4·4–5·4)], the levels of FGF23, total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol and triglycerides were measured. Standard oral glucose tolerance tests were performed with the assessment of fasting and after 120′ postload glucose and insulin levels; the insulin resistance index HOMA‐IR was calculated. Results Regardless of gender, there was a significant inverse correlation between FGF23 and fasting insulin level (r = ?0·3), as well as HOMA‐IR (r = ?0·29). Multiple regression model showed the independent association between FGF23 and HOMA‐IR. Conclusion FGF23 seems to be a novel factor contributing to insulin sensitivity. Further investigations are needed to define its role in the development of MS.     

Prognostic impact of high ABC transporter activity in 111 adult acute myeloid leukemia patients with normal cytogenetics when compared to FLT3, NPM1, CEBPA and BAALC

ATP-binding cassette transporter (and specially P-glycoprotein) activity is a well known prognostic factor in acute myeloid leukemia, but when compared to other molecular markers its prognostic value has not been well studied. Here we study relationships between this activity, fms-like tyro-sine kinase 3(FLT3/ITD), nucleophosmin(NPM1), CAAT-enhancer binding protein alpha(CEBPα), and brain and acute leukemia cytoplasmic protein (BAALC), in 111 patients with normal cytogenetics who underwent the same treatment, and evaluate its prognostic impact. Independent factors for survival were age (P=0.0126), ATP-binding cassette transporter activity (P=0.018) and duplications in the fms-like tyrosine kinase 3 (P=0.0273). In the 66 patients without fms-like tyrosine kinase 3 duplication and without nucleophosmin mutation, independent prognostic factors for complete remission achievement and survival were age and ATP-binding cassette transporter activity. In conclusion, ATP-binding cassette transporter activity remains an independent prognostic factor, and could assist treatment decisions in patients with no nucleophosmin mutation and no fms-like tyrosine kinase 3 duplication.