No Impact of Enteral Nutrition on Fecal Short-Chain Fatty Acids in Children with Cerebral Palsy.

Bacteria can impact the host organism through their metabolites, with short-chain fatty acids (SCFAs) being the most important, including acetate (C2), propionate (C3), butyrate (C4), valerate (C5n), and isovalerate (C5i). This study aimed to identify the impact of enteral nutrition on SCFAs in children with cerebral palsy and to test the hypothesis that the type of nutrition in cerebral palsy affects gut SCFA levels. Cerebral palsy is a heterogeneous syndrome resulting from non-progressive damage to the central nervous system. The study group included 30 children diagnosed with cerebral palsy, receiving enteral nutrition (Cerebral Palsy Enteral Nutrition (CPEN)) via gastrostomy. The first reference group (Cerebral Palsy Controls (CPCs)) consisted of 24 children diagnosed with cerebral palsy and fed orally on a regular diet. The second reference group (Healthy Controls (HCs)) consisted of 24 healthy children with no chronic disease and fed on a regular diet. Isolation and measurement of SCFAs were conducted using gas chromatography. Differences were observed in the median contents of isobutyric acid, valeric acid, and isovaleric acid between the CPC group, which had significantly higher levels of those acids than the HC group. No differences were found between the CPEN and CPC groups nor between the CPEN and HC groups. We conclude that enteral nutrition in cerebral palsy has no influence on the levels of SCFAs.

Does Massive Bowel Resection in Newborns Affect Further Immunity in Children?

BACKGROUND: The massive resection of the small intestine leading to short bowel syndrome (SBS) deprives an organism of many immunocompetent cells concentrated in gut-associated lymphoid tissue, the largest immune organ in humans. We have aimed to access the influence of bowel resection on adaptive immunity in children, based on peripheral lymphocyte subsets and serum immunoglobulins. METHODS: 15 children who underwent bowel resection in the first months of their life and required further home parenteral nutrition were enrolled into the study. Based on flow cytometry, the following subsets of lymphocytes were evaluated: T, B, NK, CD4+, C8+, and activated T cells. RESULTS: Statistically significant differences were found for the rates of lymphocytes B, T, CD8+, and NK cells. The absolute count of NK cells was lower in the SBS group than in the control group. Absolute counts of lymphocytes, lymphocytes B, T, CD4+, and percentages of lymphocytes CD4+, and activated T cells inversely correlated with age in SBS group. CONCLUSIONS: Children with SBS do not present with clinical signs of immunodeficiency as well as deficits in peripheral lymphocyte subsets and serum immunoglobulins. The tendency of the lymphocyte subpopulations to decrease over time points out the necessity for longer follow- up.

DeltaF508 CFTR Hetero- and Homozygous Paediatric Patients with Cystic Fibrosis Do Not Differ with Regard to Nutritional Status.

The purpose of this study was to compare the nutritional status between deltaF508 CFTR hetero- and homozygous paediatric patients with cystic fibrosis. We assessed the percentage profiles of fatty acids measured in erythrocyte membranes and the serum levels of vitamins A, D3, E and K1 in the studied groups. We also measured the weights and heights and calculated the body mass indexes (BMIs). The studied groups consisted of 34 heterozygous and 30 homozygous patients. No statistically significant differences were found in the serum vitamins or erythrocyte membrane fatty acid profiles between the hetero- and homozygous patient groups, except for heptadecanoic acid (p = 0.038). The mean percentiles of height, weight and BMI did not differ significantly between the two groups. The homozygous and heterozygous paediatric patients with cystic fibrosis were similar in terms of their nutritional statuses.

Histamine Intolerance in Children: A Narrative Review.

Histamine intolerance is defined as a disequilibrium of accumulated histamine and the capacity for histamine degradation. This clinical term addresses a non-immunologically mediated pathology when histamine ingested with food is not particularly high, however its degradation is decreased. This paper aims to provide a narrative review on etiopathology, epidemiology, possible diagnostic algorithms and diagnostic challenges of histamine intolerance in children. The clinical picture of histamine intolerance in children is similar to that observed in adults apart from male predominance found in paediatric patients. Both in children and adults, a histamine-reduced diet is typically the treatment of choice. Diamine oxidase supplementation offers another treatment option. There is no symptom or test pathognomonic for histamine intolerance. Nevertheless, manifestations of chronic gastrointestinal symptoms, measurements of diamine oxidase deficits, positive results of histamine provocation tests and improvement in symptoms with histamine-reduced diet considerably increase the probability of histamine intolerance diagnosis. These factors have been included in the proposed diagnostic algorithm for histamine intolerance. In children histamine intolerance most likely co-occurs with allergies and bowel diseases, which creates an additional diagnostic challenge. As the evidence for children is poor further research is needed the determine epidemiology, validate diagnostic algorithms and establish possible treatment options regarding histamine intolerance.

Immunogenicity of cholera vaccination in children with inflammatory bowel disease.

The cholera vaccine can protect patients with inflammatory bowel disease (IBD) against both cholera and travelers' diarrhea. However, both immunosuppressive treatment and IBD can affect its vaccine immunogenicity. The aim of this study was to assess the immunogenicity and safety of the cholera vaccine in children with IBD. Children older than 6 years with diagnosed IBD were enrolled in this multicenter study. All patients were administered two doses of the oral cholera vaccine (Dukoral®). Anti-cholera toxin B subunit IgA and IgG seroconversion rates were evaluated in a group with immunosuppressive (IS) treatment and a group without IS treatment (NIS). Immunogenicity was assessed in 70 children, 79% of whom received IS treatment. Post-vaccination seroconversion was displayed by 33% of children, for IgA, and 70% of children, for IgG. No statistically significant differences were found in the immune responses between the IS and NIS groups: 35% vs. 27% (p = .90), for IgA, and 68% vs. 80.0% (p = .16), for IgG, respectively. One case of IBD exacerbation after vaccination was reported. The oral cholera vaccine is safe. The immunogenicity of the oral cholera vaccine in children with IBD was lower than previously observed in healthy ones. The treatment type does not seem to affect the vaccine immunogenicity.

No Evidence for Sex-specificity in Vitamins C, E, and Fatty Acid Content of Human Milk from Healthy Polish Mothers.

OBJECTIVES: Human milk (HM) is a complex fluid that meets the nutritional needs of infants. Its composition is associated with environmental, maternal, and fetal variables. It provides nutrients and bioactive substances, including cytokines, immunoglobulins, and constituents with antioxidative properties. Boys are reportedly more susceptible to oxidative stress. This study aimed to determine the relationship between infant sex and the antioxidants vitamins C and E, and the fatty acid (FA) profile of HM. Results of this investigation may infer sex differences for the composition of infant formulas. METHODS: Thirty days after delivery, a sample of HM was collected from 152 healthy, non-smoking mothers of full-term new-borns (77 males) born in good clinical condition. After FAs were extracted from the fat component, they were converted into methyl esters and separated using high-performance gas chromatography. Tocopherol content was determined using a method described in a previous study. Vitamin C content was determined using reversed-phase high-performance liquid chromatography with ultraviolet detection, as described in the same study. RESULTS: The study groups (male vs female offspring) did not differ in terms of vitamin and FA content in HM. The only difference found was in gondoic acid 20:1 (n-9), with a higher concentration in the HM of mothers with female offspring (mean 0.63 ±â€Š0.18 vs 0.59 ±â€Š0.15 g/100 g FA; P < 0.047). CONCLUSIONS: Despite the acknowledged differences in the composition of HM associated with infant sex and the increased oxidative stress in males, antioxidant content did not appear to differ according to infant sex. These results suggest that there is no need for the antioxidant content of infant formulas to be sex-specific.

Enhancement of Circulating and Intestinal T Regulatory Cells and Their Expression of Helios and Neuropilin-1 in Children with Inflammatory Bowel Disease.

BACKGROUND/AIMS: The proportions of intestinal and peripheral regulatory T cells (Tregs) in pediatric inflammatory bowel disease (IBD) were poorly investigated, as well as different subsets of these cells. Helios and Neuropilin-1 were proposed as markers differentiating between thymic and peripheral Tregs. Therefore, the aim of current work was to investigate the proportions of Tregs and expression of Helios and Neuropilin-1 in Tregs in peripheral blood and intestinal mucosa of children with inflammatory bowel disease. MATERIALS AND METHODS: Fifteen patients newly diagnosed with inflammatory bowel disease: ulcerative colitis (n=7) and Crohn's disease (n=8) were included in the study. Nine children who presented with no abnormalities in colonoscopy served as a control group. Quantification of regulatory T cells of the CD4+CD25highFOXP3+ phenotype, as well as Helios+ and Neuropilin-1+ in peripheral blood and bowel mucosa was based on multicolor flow cytometry. RESULTS: The rates of circulating and intestinal Tregs were significantly higher in the studied group than in the control group. The rate of intestinal T regulatory lymphocytes was significantly higher than circulating Tregs in patients with IBD, but not in the control group. The median proportion of circulating FOXP3+Helios+ cells amounted to 24.83% in IBD patients and 15.93% in the controls. The median proportion of circulating FOXP3+Nrp-1+ cells was 34.23% in IBD and 21.01% in the control group. No statistically significant differences were noted for the circulating FOXP3+Helios+ cells and FOXP3+Nrp-1+ cells between the studied and the control group. CONCLUSION: The rates of circulating and intestinal T regulatory cells are increased in naïve pediatric patients with IBD. The rate of Tregs is higher in intestinal mucosa than in peripheral blood in patients with IBD. Flow cytometry is a valuable method assessing the composition of infiltrates in inflamed tissue. Helios and Neuropilin-1 likely cannot serve as markers to differentiate between natural and adaptive Tregs.

Serum chemerin level, cytokine profile and nutritional status in children with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is characterized by malnutrition and chronic inflammation predominantly occurring in lungs. Evidence suggests a relation between inflammatory activity and nutritional status. Proinflammatory cytokines, playing crucial role in pulmonary destruction in CF, are regarded as a component of the pathogenesis of illness-related malnutrition. Chemerin - a novel marker of a crosstalk between nutrition and inflammation, has not been investigated in children with cystic fibrosis. The aim of this study was to determine serum level of chemerin, interleukin-1b (IL-1b), interleukin-6 (IL-6), tumor necrosing factor α (TNF-α) and interleukin-10 (IL-10) and to verify if they correlate with the nutritional status in children with CF. METHODS: The study included 72 pediatric patients with cystic fibrosis. The control group was comprised of 30 healthy children. Nutritional status parameters: Body Mass Index (BMI), fat mass percentage (FM %) and fat free mass percentage (FFM%) have been assessed in all the subjects basing on bioimpedance and anthropometry according to Slaughter. Serum concentrations of chemerin and cytokines were estimated with ELISA. RESULTS: No statistically significant difference in serum chemerin was found between the studied and the control group. We have documented a significantly higher level of IL-1b, IL-6, TNF-α and IL-10 in CF patients when compared to healthy controls. Neither the chemerin nor the cytokine levels correlated with parameters of nutritional status in our cohort. No statistically significant correlation was found between the serum chemerin and the inflammatory cytokines: IL-1b, IL-6, and TNFα. CONCLUSIONS: Our results show that chemerin is not associated with the nutritional status in children with cystic fibrosis. Chemerin has no impact on the levels of IL-1b, IL-6, TNFα in CF patients. IL-1b, IL6, TNFα and also IL10 are upregulated in cystic fibrosis.

Peripheral regulatory T cells and anti-inflammatory cytokines in children with juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a chronic, heterogenous inflammatory disease of unclear pathogenesis. JIA is hypothesized to be linked to a defective immune regulation. Anti-inflammatory cytokines belong to the best known regulatory factors. T-regulatory cells are a crucial cellular component of immune tolerance. One of their functions is synthesis of interleukin 10 (IL-10) and transforming growth factor beta1 (TGF-ß1). The aim of this study was to determine the proportion of T-regulatory cells (CD4+CD25highFOXP3+) in peripheral blood, and serum levels of TGF-ß1 and IL-10 in patients with JIA. METHODS: The study included 25 patients with newly diagnosed JIA: oligoarthritis (n=17) and polyarthritis (n=8). The control group was comprised of 17 healthy children. CD4+CD25highFOXP3+ T cells in peripheral blood were quantified by means of three-color flow cytometry. Serum concentrations of TGF-ß1 and IL-10 were estimated with ELISA. RESULTS: The proportion of peripheral CD4+CD25highFOXP3+ cells in patients with JIA was significantly higher than in the controls (p=0.04). The two groups did not differ significantly in terms of their TGF-ß1 and IL-10 concentrations. CONCLUSIONS: At the time of diagnosis, children with JIA presented with an elevated proportion of T-regulatory cells (CD4+CD25highFOXP3+) in peripheral blood. Anti-inflammatory cytokines, IL-10 and TGF-ß1, are not upregulated in the serum of patients with JIA, and therefore should not be considered as biomarkers of this condition.

PD-L1 expression on immune cells is a favorable prognostic factor for vulvar squamous cell carcinoma patients.

BACKGROUND: Anti-immune programmed death-ligand 1 (PD-L1) pathway is used by the tumor to overcome immune system and serves as immunotherapy target in various malignancies. AIM: To investigate the expression of PD-L1 in vulvar squamous cell carcinoma (vSCC) and to assess it's clinicopathological and prognostic significance. METHODS: Immunohistochemical PD-L1 expression was evaluated in 84 vSCCs with previously defined status of p16 and DNA-HPV, infiltration of immune cells: CD8+, CD4+, FOXP3+, CD56+, CD68+, and GZB+ cells. PD-L1 positivity was defined as ≥5% of PD-L1-positive cells. Survival analyses included the Kaplan-Meier method, log-rank test and Cox proportional hazards model. RESULTS: PD-L1 expression was detected on cancer and peritumoral immune cells. PD-L1-positivity of cancer nests (27/84, 32.1%) was correlated with higher infiltration of CD4+ (p=0.037), CD8+ (p=0.02), FOXP3+ (p=0.007), CD68+ (p=0.021) cells, while PD-L1 positivity of peritumoral immune cells (51/84, 60.7%) was correlated with higher infiltration of intraepithelial FOXP3+ cells only (p=0.037).PD-L1-positivity of cancer cells but not immune cells, was more frequently observed in p16-negative tumors (p=0.004). High-risk HPV-status did not correlate with the PD-L1 status of cancer and immune cells (p=1.000) and (p=1.000) respectively). Median follow up was 89.20 months (range 1.7-189.5). PD-L1 positivity of peritumoral immune cells was found to be an independent favorable prognostic factor for OS. Conclusion: This study highlights the importance of comprehensive PD-L1 assessment in both cancer and immune cells. PD-L1 expression on peritumoral immune cells seems to be an additional prognostic factor in vSCC patients and may influence the results by anti-PD-L1 treatment.

Association between uridin diphosphate glucuronosylotransferase 1A1 (UGT1A1) gene polymorphism and neonatal hyperbilirubinemia.

OBJECTIVE: To assess the prevalence of UGT1A1*28 and UGT1A1*60 polymorphisms of UGT1A1 gene and their association with hyperbilirubinemia. STUDY DESIGN: The study was performed at a single centre - at the Department of Obstetrics of the Medical University of Gdansk in Poland. DNA was isolated from Guthrie cards of 171 infants. Only full term newborns (gestational age 38-42 weeks) were included in the study. Fluorescent molecular probes were used for UGT1A1 promoter variation analysis. The presence of UGT1A1*28 polymorphism was detected with a dual-probe system, and UGT1A1*60 with a SimpleProbe™. RESULT: Homozygous UGT1A1*28 and UGT1A1*60 genotypes were detected in 14.6% and 20.5% of the newborns, respectively. Homozygous (G/G) genotypes of UGT1A1*60 polymorphism were found in all of the UGT1A1*28 (i.e. (TA)7/(TA)7) homozygotes. More than 80% (55/66) of the children with "wild" type UGT1A1*28 genotype (where no polymorphism was detected) (i.e. (TA)6/(TA)6) carried the "wild" (T/T) genotype of UGT1A1*60 as well. The UGT1A1*28 polymorphism was detected more often among neonates with elevated bilirubin. Hyperbilirubinemia was diagnosed more frequently in boys. CONCLUSION: Polymorphisms of the UGT1A1 gene frequently co-exist in neonates. The presence of UGT1A1*28 polymorphism and male gender seem to predispose to neonatal hyperbilirubinemia.

A new topical panthenol-containing emollient: skin-moisturizing effect following single and prolonged usage in healthy adults, and tolerability in healthy infants.

PURPOSE: Two studies were conducted with a new topical panthenol-containing emollient (NTP-CE) to investigate the skin-moisturizing effect in healthy adults and tolerability in healthy infants. METHODS: In Study 1 (N = 44), a single skin application of NTP-CE was performed followed by a 4-week twice-daily application. Skin hydration and stratum corneum (SC) water content change (using Raman spectroscopy) were measured. In the 4-week Study 2 (N = 65, aged 3-25 months), NTP-CE tolerability was assessed using a 5-point scoring system; skin hydration was determined in a subset (N = 21). RESULTS: In Study 1, mean AUC0 - 24 h for skin capacitance change from baseline was 302.03 i.u. with NTP-CE and -15.90 i.u. in control areas (p < .001). With NTP-CE (at 4 h), the water content within the upper SC part was reduced (-45.10 vs. -13.39 g/cm2, p = .013) and the water gradient increased (0.51 vs. 0.11 g/cm4, p = .036), indicating relocation of water into deeper layers. In Study 2, there was no statistically significant change from baseline in mean cutaneous tolerability scores. At days 7, 14, and 28, skin hydration had increased by 42%, 54%, and 49%, respectively (all p < .001). CONCLUSIONS: Single and prolonged NTP-CE usage is associated with sustained and deep skin moisturization. NTP-CE is well tolerated by healthy infants.

Peripheral and Intestinal T-regulatory Cells are Upregulated in Children with Inflammatory Bowel Disease at Onset of Disease.

BACKGROUND/AIMS: To determine the proportion of T-regulatory cells (CD4+CD25highFOXP3+ cells) in peripheral blood and the number of FOXP3+ cells in intestinal mucosa of children with inflammatory bowel disease (IBD), and to verify whether these parameters correlate with the activity of the disease. MATERIAL AND METHODS: 24 patients newly diagnosed for IBD were included in the study: ulcerative colitis (UC; n = 13) and Crohn's disease (CD; n = 11). Seventeen healthy controls (HC) and 16 patients with irritable bowel syndrome (IBS) served as a control group for peripheral and intestinal Tregs assessment, respectively. The disease activity was assessed by Pediatric Ulcerative Colitis Activity Index (PUCAI) and Pediatric Crohn's Disease Activity Index (PCDAI). Quantification of regulatory T cells of CD4+CD25highFOXP3+ phenotype in peripheral blood was based on three-color flow cytometry. Mucosal Tregs represented by FOXP3+ cells were evaluated using immunohistochemistry. RESULTS: Median proportion of CD4+CD25highFOXP3+ cells among CD4+ T cells in peripheral blood (5.1%, range 1.7-84% vs. 4.3%, range 2-8.1%, p = 0.023) and median number of intestinal FOXP3+ cells (115.33 per high-power field, hpf, range 39.33-375.67 vs. 10.16 per hpf, range 5-30, p = 0.0001) were significantly higher in children with IBD than in the controls. The proportion of circulating Tregs and the number of intestinal FOXP3+ cells did not correlate with clinical activity of the disease, as well as with endoscopic and histopathologic scoring. No significant correlation was found between the percentage of peripheral CD4+CD25highFOXP3+ cells and the number of intestinal FOXP3+cells. CONCLUSIONS: Children with IBD likely do not present with a quantitative deficiency of circulating and intestinal Tregs at the moment of diagnosis.

Evaluation of clinical usefulness of serum neopterin determination in children with bacterial infections.

UNLABELLED: Neopterin (NPT) (6-D-erythro-trihydroxypropyl pteridin) is one of the indicators of the immune system activity. Elevated neopterin concentration occurs in diseases mostly involving stimulation of cellular immunity. The determination of neopterin concentration, usually in blood serum and urine but also in many other bodily fluids, has already been applied in many areas of medicine, such as transfusiology, transplantology, oncology, infectious diseases and autoimmunological diseases. OBJECTIVE: The aim of this work is to evaluate clinical usefulness of serum neopterin determination in children with urinary tract infections of confirmed bacterial etiology. MATERIAL: The study involved 56 children with bacterial urinary tract infections - patients of the Clinic of Paediatrics, Paediatric Gastroenterology, Hepatology & Paediatric Nutrition of Medical University of Gdansk in the years 2012-2013. The control group included 105 healthy children. RESULTS: The values of NPT concentration in blood serum obtained in the group of children with urinary tract infections did not significantly differ from the values obtained in the control group. CONCLUSIONS: The determination of neopterin concentration in children with bacterial urinary tract infections is not a clinically useful parameter.

Graves' disease, Celiac disease and liver function abnormalities in a patient--clinical manifestation and diagnostic difficulties.

Autoimmune diseases due to probable common pathogenesis tend to coexist in some patients. Complex clinical presentation with diverse timing of particular symptoms and sophisticated treatment with numerous side effects, may cause diagnostic difficulties, especially in children. The paper presents diagnostic difficulties and pitfalls in a child with Graves' disease, celiac disease and liver function abnormalities.

Reorganization of nutritional therapy can markedly reduce the rate of catheter-related blood stream infections in pediatric patients receiving parenteral nutrition - a 7-year prospective follow-up study.

BACKGROUND: Implementation of hygienic measures and simple changes in the structure of medical team may considerably reduce the rate of catheter-related bloodstream infections (CRBSIs) in parenterally nourished patients. AIM: To analyze the effects of organizational changes in parenteral nutrition services on the CRBSI rates in pediatric patients. METHODS: We compared the CRBSI rates documented prior to, during and after the implementation of the organizational changes (introduction of a nutritional support team and related procedures, medical staff training). FINDINGS: A total of 260 courses of parenteral nutrition were offered to 141 pediatric patients during the analyzed period. Thirty CRBSIs were documented during this period. The most frequent etiological factors were staphylococci (21/30), followed by Klebsiella pneumoniae, Escherichia coli and Candida albicans (2/30 each). The reorganization was reflected by more than 8-fold reduction of the CRBSI incidence rate: from the initial value of 10.14 to 6.89 per 1000 catheter days and 1.17 per 1000 catheter days during and after the reorganization, respectively. CONCLUSION: Introduction of a nutritional support team, accompanied by extensive training of medical staff, can result in a marked reduction of CRBSI rate in pediatric patients nourished parenterally in a hospital setting.

Antecedentes: La implementación de medidas higiénicas y cambios sencillos en la estructura del personal médico puede reducir considerablemente la tasa de bacteriemia asociada al catéter (BAC) en pacientes que reciben nutrición parenteral. Objetivo: Analizar el impacto de los cambios organizacionales dentro de los servicios de nutrición parenteral sobre las tasas de BAC en pacientes pediátricos. Métodos: Hemos comparado las tasas de BAC documentadas antes, durante y después de la implementación de los cambios organizacionales (introducción de un grupo de apoyo nutricional y los procedimientos relacionados, formación del personal médico). Descubrimientos: Un total de 260 series de nutrición parenteral fueron ofrecidos a 141 pacientes pediátricos durante el periodo analizado. Se documentaron treinta BAC durante este periodo. Los factores etiológicos más frecuentes eran staphylococci (21/30), seguidos por Klebsiella pneumoniae, Escherichia coli y Candida albicans (2/30 cada uno). Los cambios organizacionales fueron reflejados en una reducción de la incidencia de BAC en más de 8 veces: el valor inicial disminuyó desde 10.14 hasta 6.89 por 1000 días-catéter y hasta 1.17 por 1000 días-catéter durante y después de la reorganización, respectivamente. Conclusión: La introducción de un grupo de apoyo nutricional, acompañada de una extensa formación del personal médico puede resultar en una reducción considera ble de la tasa de BAC en pacientes pediátricos que reciben nutrición parenteral en en un entorno hospitalario.

Serum Concentrations of Tryptase in Children.

Background: Mast cells are dispersed in many tissues, especially in digestive and respiratory-tract mucosal membranes. Tryptase, considered a marker of mast-cell activity, is the most important protease released from these cells during degranulation. Tryptase concentration is mainly accessed in anaphylaxis and mastocytosis, being one diagnostic criteria of this disease. There are no data concerning tryptase activity in healthy children in the current literature. Aim: The aims of this study were the analysis of concentrations of serum tryptase in healthy children, and determining reference values of the enzyme at different developmental ages. Materials and methods: The investigated group consisted of 131 healthy children (75 girls, 56 boys) aged 3 months-18 years. The concentration of tryptase in the studied samples was evaluated by the fluoro-immuno-enzymatic method with UniCAP. Results: The mean concentration of serum tryptase in the studied group was 2.8±2.2 ng/dL: 2.5±2.2 ng/dL in girls and 3.2±2.1 ng/dL in boys. Conclusion: The upper reference limit of 7.2 ng/dL was lower than in adults.

Expression of indoleamine 2,3-dioxygenase predicts shorter survival in patients with vulvar squamous cell carcinoma (vSCC) not influencing on the recruitment of FOXP3-expressing regulatory T cells in cancer nests.

OBJECTIVE: Regulatory T cells (Tregs), and the enzyme indoleamine 2,3-dioxygenase (IDO), have potential regulatory properties for immune escape in cancer. Inhibitors of IDO are available and could potentially be used in vulvar cancer if IDO was proved to drive progression of the disease. The aim of this study was to evaluate the expression of factor forkhead boxP3 (FOXP3), a marker of Tregs, and IDO in vulvar squamous cell carcinoma (vSCC), and to verify their prognostic significance. METHODS: 76 primary tumors and 35 lymph node metastases derived from 76 patients with full clinical history were analyzed. The intratumoral infiltration of Tregs and IDO expression within cancer were evaluated by immunohistochemistry. RESULTS: The number of Tregs in primary tumor and in corresponding lymph node metastasis was significantly correlated. Intensity of Treg infiltrates in the primary and metastatic sites was not correlated to IDO expression and had no influence on the overall patient survival. High IDO expression was associated with significantly worse overall survival among vSCC patients and was found to be an independent prognostic factor similarly to the tumor grade and patient's age. CONCLUSIONS: The degree of intratumoral Treg infiltrates is an individual feature and remains stable throughout the course of the disease without impact on the patient's survival. IDO expression predicts shorter survival of vSCC patients. If immunologic tolerance of the tumor is promoted by the overexpression of IDO it will not influence the number of intratumoral Tregs. IDO expression seems to be an independent prognostic factor in patients with vSCC.

[Gene polymorphism of transforming growth factor beta1 (TGF-beta1) in the pathogenesis and clinical course of chronic hepatitis in children]. / Polimorfizm genu transformujacego czynnika wzrostu beta1 (TGF-beta1) w etiopatogenezie i przebiegu klinicznym przewleklych zapalen watroby u dzieci.

UNLABELLED: Transforming growth factor beta1 (TGF-beta1) is a cytokine modulating the immune response. The role of TGF-beta1 gene polymorphisms in the incidence and modification of the clinical course of these diseases has been recently evaluated. THE AIM of the study was to assess the relation between TGF-beta1gene polymorphism and the incidence of chronic hepatitis, the course of the disease, TGF-beta1 level in plasma and TGF-beta1 mRNA expression in liver tissue. PATIENTS AND METHODS: The studied group comprised 21 patients with chronic hepatitis including 10 with HBV infection, 4 with HCV infection and 7 with autoimmune hepatitis (AIH). Forty-two children were included in the control group. Analysis of four studied polymorphisms of TGF-beta1 gene was based on CAPS (Cleaved Amplified Polymorphic Sequence) method, TGF-beta1 level in plasma was estimated using sandwich ELISA. TGF-beta1 mRNA expression was evaluated by reverse transcription and real-time polymerase chain reaction (Real-Time PCR). RESULTS: No correlation between studied polymorphisms and the incidence or clinical course of chronic hepatitis was found. There were no significant differences in TGF-beta1 level in plasma and mRNA expression depending on polymorphisms of TGF-beta1 gene. CONCLUSIONS: 1. The polymorphisms of TGF-beta1 gene do not appear to influence the incidence and clinical course of chronic hepatitis in children. 2. Due to relatively low number of patients in the analysed groups it seems advisable to perform similar complex studies in larger groups of children with chronic hepatitis.

[Analysis of risk factor treatment failures in therapeutic programme for malignant germ cell tumours in children. Multicentre prospective study of Polish Pediatric Group for Solid Tumours 1998--2006]. / Analiza czynników ryzyka niepowodzenia terapii w programie leczenia dzieci ze zlosliwymi guzami terminalnymi. Wieloosrodkowe badania prospektywne Polskiej Pediatrycznej Grupy Guzów Litych (PPGGL) w Latach 1998--2006.

AIMS: The aim of the study was the analysis of risk factors of therapeutic failures in children with malignant germ cell tumours treated within the multicentre programme of PPGGL from 1999--2006. MATERIALS AND METHODS: The investigated group included 18 (14.3%) patients, of 123 who have finished the treatment of malignant germ cell tumour, in whom no remission was obtained or relapse occurred. All the patients were treated according to the TGM 95 programme. Both clinical and morphological data of the group have been analysed. RESULTS: Among 18 patients with therapeutic failures 12 died. Two patients from the high risk group died of complications of the treatment--sepsis during neutropenia after chemotherapy and one after haemorrhage to the central nervous system. The other 9 died from progression of malignancy, 6 of them belonged to the high risk group. 10 (82%) of 12 patients who died had extragonadal location and in 11 (92%) the tumour was in stage III or IV of the disease. The most frequent histology in this group was mixed germ cell tumour with component of yolk sac tumour or carcinoma embrionale. 92% patients had elevated AFP, in 4 it was above 15000 ng/ml. In 11 (92%) patients primary chemoresistance was observed, and radical surgery was not possible for the reason of advanced stage of the disease. In 6 patients relapse occurred. In 3 patients testis was the primary location (I and II stage), in 3 patients the tumour was localized in the sacrococcygeal region (III and IV stage). All the patients are alive in remission after second line therapy, with 78 months (median) of follow-up. CONCLUSIONS: 1. The main risk factor for therapeutic failures in malignant germ cell tumours was primary chemoresistance in inoperable tumours of the sacrococcygeal region. 2. The mortality of treatment complications was low. 3. The relapse of cancer was not a risk factor for therapeutic failure due to the high probability of second remission 4. Therapeutic failures are mainly observed in patients with mixed germ cell tumour with components of yolk sac tumour or carcinoma embrionale. 5. Tumour chemoresistance should be considered an essential factor in identifying high risk patients.