The Interferon-Gamma Release Assay versus the Tuberculin Skin Test in the Diagnosis of Mycobacterium tuberculosis Infection in BCG-Vaccinated Children and Adolescents Exposed or Not Exposed to Contagious TB.

BACKGROUND: Children have an increased risk of developing active tuberculosis (TB) after exposure to Mycobacterium tuberculosis (M.tb), and they are more likely to develop the most severe forms of TB. Rapid diagnosis and treatment of latent M.tb infection (LTBI) is essential to lessen the devastating consequences of TB in children. OBJECTIVE: The aim of the study was to evaluate TST (tuberculin skin test) and IGRA (interferon-gamma release assay) utility in identifying LTBI in a cohort of Bacille Calmette-Guérin (BCG)-vaccinated Polish children and adolescents exposed or not exposed to contagious TB. In addition, we asked whether quantitative assessment of IGRA results could be valuable in predicting active TB disease. RESULTS: Of the 235 recruited volunteers, 89 (38%) were TST-positive (TST+), 74 (32%) were IGRA-positive (IGRA+), and 62 (26%) were both TST+ and IGRA+. The frequency of TST positivity was significantly higher in the group with (59%) than without TB contact (18%). The percentage of TST+ subjects increased with age from 36% in the youngest children (<2 years) to 47% in the oldest group (>10 years). All positive IGRA results were found solely in the group of children with TB contact. There was a significant increase in the rate of positive IGRA results with age, from 9% in the youngest to 48% in the oldest group. The 10 mm TST cutoff showed good sensitivity and specificity in both TB exposed and nonexposed children and was associated with excellent negative predictive value, especially among nonexposed volunteers. Mean IFN-γ concentrations in IGRA cultures were significantly higher in the group of LTBI compared to the children with active TB disease, both TST+ and TST-. CONCLUSIONS: Both TST and IGRA can be used as screening tests for BCG-vaccinated children and adolescents exposed to contagious TB.

Brain-Derived Neurotrophic Factor (BDNF) as an Indicator for Effects of Cognitive Behavioral Therapy (CBT): A Systematic Review.

Brain-derived neurotrophic factor (BDNF) is a protein affecting survival of existing neurons and neuronal maturation. Patients suffering from several mental disorders exhibit reduced BDNF levels comparing to healthy population. In this systematic review we aim to evaluate the effect of broadly defined cognitive behavioral therapy (CBT) on BDNF levels in psychiatric patients. A literature search was performed using PubMed and Google Scholar data bases. The resources were searched between 14 January and 3 February 2022. Following the inclusion criteria, a total of 10 randomized-controlled trials were included. The results of our research indicate that BDNF levels might be considered an indicator of a result achieved in psychotherapy of cognitive functions. However, no such correlation was observed for mindfulness-based practices intended to lower stress levels or improve the quality of life. It is important to notice that present research showed no consistent correlation between the increase in BDNF levels and the perceived effectiveness of the procedures. Thus, the exact role of BDNF remains unknown, and so far, it cannot be taken as an objective measure of the quality of the interventions.

Cytokine Biosignature of Active and Latent Mycobacterium Tuberculosis Infection in Children.

None of the currently used diagnostic tools are efficient enough in diagnosing Mycobacterium tuberculosis (M.tb) infection in children. The study was aimed to identify cytokine biosignatures characterizing active and latent tuberculosis (TB) in children. Using a multiplex bead-based technology, we analyzed the levels of 53 Th17-related cytokines and inflammatory mediators in sera from 216 BCG-vaccinated children diagnosed with active TB (TB) or latent TB (LTBI) as well as uninfected controls (HC). Children with active TB, compared to HC children, showed reduced serum levels of IL-17A, MMP-2, OPN, PTX-3, and markedly elevated concentrations of APRIL/TNFSF13. IL-21, sCD40L, MMP-2, and IL-8 were significantly differentially expressed in the comparisons between groups: (1) HC versus TB and LTBI (jointly), and (2) TB versus LTBI. The panel consisting of APRIL/TNFSF13, sCD30/TNFRSF8, IFN-α2, IFN-γ, IL-2, sIL-6Rα, IL-8, IL-11, IL-29/IFN-λ1, LIGHT/TNFSF14, MMP-1, MMP-2, MMP-3, osteocalcin, osteopontin, TSLP, and TWEAK/TNFSF12 possessed a discriminatory potential for the differentiation between TB and LTBI children. Serum-based host biosignatures carry the potential to aid the diagnosis of childhood M.tb infections. The proposed panels of markers allow distinguishing not only children infected with M.tb from uninfected individuals but also children with active TB from those with latent TB.

Usefulness of parametric renal clearance images in the assessment of basic risk factors for renalnal clearance images in the assessment of basic risk factors for renal scarring in children with recurrent urinary tract infections.

BACKGROUND: Clinically confirmed incidents of acute pyelonephritis (APN) following recurrent infections of urinary tract (UTI) form basic risk factors for renal scarring in children. Vesico-uretheral reflux (VUR) of higher grade is additional risk factor for this scarring. Opinions on diagnostic value of summed sequential images of renal uptake phase (SUM) of dynamic renal scintigraphy in detection of renal scars are diverse. However, several publications point to higher diagnostic efficacy of clearance parametric images (PAR) generated from this study. THE AIM OF THE STUDY: To establish a clinical value of parametric renal clearance images in detection of renal scarring. MATERIAL AND METHODS: A prospective study was performed in a group of 91 children at the age of 4 to 18 years with recurrent UTI. Clinically documented incidents of APN were noted in 32 children: in 8 cases - one and in the remaining 24 - 2 to 5 (mean 3) incidents. In the remaining 59 patients only infections of the lower part of urinary tract were diagnosed. Static renal 99mTc-DMSA SPECT study and after 2-4 days dynamic renal studies (99mTc-EC) were performed in every patient not earlier than 6 months after the last documented incident of UTI. PAR images generated from a dynamic study by in-house developed software and SUM images were compared with a gold standard SPECT study. RESULTS: Percentages of children with detected renal scar(s) with SPECT and PAR methods amounted to 55% and 54%, respectively and were statistically significantly higher (p < 0.0001) than with SUM method - 31%. Scars in children with history of APN detected with SPECT and PAR methods were significantly more frequent than with infections of only lower part of urinary tract (72% vs. 46%; p = 0.017 and 69% vs. 46%; p = 0.036, respectively). A SUM method did not reveal statistically significant differences between frequencies of detection of scars in groups specified above - 38% vs. 27% (p = 0.31). Both SPECT and PAR methods showed also that frequencies of occurrence of renal scars in children with higher grades of VUR were higher than without or with lower grades of VUR: 79% vs. 50% (p = 0.048) and 79% vs. 49% (p = 0.04). A SUM method did not reveal higher frequency of renal scars in children with high VUR grades: 36% vs. 30% (p = 0.44). CONCLUSION: Results obtained with PAR and SPECT methods were similar. An advantage of PAR over SUM images obtained from a dynamic renal scintigraphy in detection of renal scars in children with UTI was confirmed.

[Chlamydophila pneumoniae infections in younger children. Experience of one centre. Preliminary report]. / Zakazenia chlamydophila pneumoniae u dzieci mlodszych. Doswiadczenia jednego osrodka. Doniesienie wstepne.

BACKGROUND: Very few recent Polish data are available on the epidemiology of Chlamydophil pneumoniae (C. pneumoniae) as causative agent among paediatric patients, hospitalized with respiratory tract disorders. Extending these data would serve as rationale for empirical antimicrobial therapy. The aim of the study was to evaluate the frequency of C. pneumoniae infections in younger children hospitalized with prolonged cough and/or prolonged pneumonia. MATERIAL AND METHODS: 110 children, aged 0.3-7.0 yrs., hospitalized from January 1st to March 3 1st 2009 for the above reasons were retrospectively enrolled in the study. Diagnosis of C. pneumoniae was based on ELISA IgM antibodies positive test. Patients with ambiguous IgM titre were excluded from further study (n=12). RESULTS: Of 98 finally investigated children, C. pneumoniae infection was found in 28 patients (28.5%) with the highest frequency in February 2009 (15 cases). It was diagnosed more frequentlyin toddlers (over 1.73 yrs. of age) than in infants and youngest children (p=0,014; OR=4,10 95%C1=1,4-12,0). In patients with active C pneumoniae infection WBC were significantly lower (p=0,001), but within normal range (8647/mm3, +/- SD: 3247/mm3). Other factors such as sex, clinical symptoms and some chosen laboratory markers did not differ significantly between subgroups of sero-positive/sero-negative patients. CONCLUSIONS: Performed analysis suggests a significant role of C. pneumoniae etiology in younger children with prolonged respiratory tract symptoms and can be a useful tool in empirical antibacterial treatment. Further studies for a longer period, larger groups of patients and additional confirmation of sero-positive cases are needed.

Assessment of clinical usefulness of parametric clearance images in diagnosis of kidney cicatrisation in children with chronic infections of the urinary tract.

BACKGROUND: Cicatrisation of the renal cortex is closely related to chronic infections of the urinary system. Static renal scintigraphy is used as the method enabling detection of local defects of radiopharmaceutical uptake, and is treated as the "gold standard" in the diagnosis of renal scars. The aim of the reported investigation was a comparison of the diagnostic efficacy of parametric clearance images and the conventional summation images - obtained from dynamic scintigraphy - in the detection of local defects of renal function. As the "gold standard" for the above comparison, the static scintigraphy of kidneys was accepted. MATERIAL AND METHODS: Forty-one patients (age 4-19 years), 28 girls and 13 boys, participated in the study. Altogether, 73 kidneys were analyzed (in 9 patients, only one kidney). In each patient dynamic renal scintigraphy was performed after IV administration of 99mTc EC (ethylenedicysteine) and static planar renal scintigraphy using 99mTc-DMSA (dimercaptosuccinic acid) as a reference method. From the dynamic study, summation and parametric clearance images were generated. Each kidney was divided into 3 segments (upper, middle, lower); altogether 219 segments were evaluated by modified Howard's scale. Planar and oblique projection images were compared with corresponding summation and parametric clearance images. RESULTS AND CONCLUSIONS: Parametric clearance imaging has a higher sensitivity and accuracy for detection of regional post-inflammatory changes in the kidneys than conventional summation images (p < 0.05) and shows parenchymal changes similarly to static scintigraphy (high Cohen's kappa index).

TGF-beta1 gene polymorphisms and primary vesicoureteral reflux in childhood.

The aim of this study was to assess the association between the transforming growth factor-beta1 (TGF-beta1) gene polymorphisms rs1800469 (commonly known as T-509C) and rs1982073 (commonly known as Leu (10)-->Pro) and primary vesicoureteral reflux (VUR) and renal scarring. Using a case-control approach, we examined 121 children with primary VUR and 169 controls. Genotyping of the TGF-beta1 gene polymorphisms was performed by restriction fragment length polymorphism (RFLP) analysis. The (99m)Tc-DMSA- or (99m)Tc-unitiol-single photon emission computed tomography method was used to evaluate renal scars in 84 of 121 VUR children. Statistical analysis revealed differences in rs1800469 genotype frequencies between VUR patients and controls (p = 0.0021). Our data demonstrate that individuals homozygous for the TT genotype are at risk of primary VUR [odds ratio (95% confidence interval) = 2.7 (1.46-5.08)]. Distribution of the rs1982073 polymorphism was similar in VUR children and controls. In terms of renal scarring, patients were stratified into non-scar and scar subgroups, and no differences in the genotype frequencies of either polymorphism was found. Previous reports have shown that the TT genotype of the rs1800469 polymorphism is a risk factor for renal scarring in primary VUR, and the results of our study suggest that this same polymorphism is associated with susceptibility to this congenital uropathy.

[Evaluation of the podocytes in urine in the nephrotic syndrome in childhood]. / Ocena podocytów w osadzie moczu u dzieci z zespolem nerczycowym.

UNLABELLED: The pathogenesis of nephrotic syndrome in childhood is still not clear. In most cases minimal change disease, diffuse mesangial proliferation or focal and segmental glomerulosclerosis (FSGS) cause the nephrotic syndrome. To date many studies have revealed that podocytes are the major players in the pathogenesis. The loss of podocytes in urine resulting in podocytopenia is involved in the development of the FSGS. THE AIM OF THE STUDY: We introduced the method of detection of the podocytes in urine and evaluated the podocytes in urine and their association with the clinical course of the idiopathic nephritic syndrome in childhood. We also preliminary estimated this method as a diagnostic tool. MATERIAL AND METHODS: The study group consisted of 50 children with nephrotic syndrome. The podocytes in urine were identified by antibodies against podocalyxin with immunofluorescence method. Statistical analysis looking for correlations between clinical characteristic of nephrotic syndrome and podocyturia was done. RESULTS: Podocyturia was detected in 6 patients. No correlation between clinical characteristic of nephrotic syndrome and podocyturia was found. CONCLUSIONS: Podocyturia is not a constant sign. Podocyturia does not correlate exclusively with FSGS and is present in different histopathological types of glomerulonephritis. Podocyturia does not correlate with proteinuria and clinical characteristics of nephrotic syndrome. Evaluation of the podocyte presence in urine may be a valuable fulfillment of the standard diagnostic methods in glomerulopathies, but its role in the differential diagnosis of glomerulopathies needs further studies.

Cortical scintigraphy in the evaluation of renal defects in children with vesico-ureteral reflux--optimization of the procedure and study interpretation.

BACKGROUND: The objective of this study was to analyse the performance of several variants of kidney scintigraphy in children from the standpoint of: scar detection, an assessment of the rating of the pathology and an investigation of interobserver variability involved in the diagnostic procedure. MATERIAL AND METHODS: The analysis is based on results of a planar kidney scintigraphy and of a tomographic (SPECT) procedure. The latter was performed in two variants: 1) in which slices were obtained with axis of reconstruction identical with longitudinal axis of the body (SPECT I) and 2) in which axes were fitted to the long axis of each kidney separately (SPECT II). The rating of the diagnosed pathology was made using two scales, according to Goldraich and Howard. Evaluation of the images involved on the one hand, 150 individual kidneys and 75 patients on the other. The assessment was made by three independent observers, differing in experience in nuclear medicine and employed in three independent departments. In the statistical analysis, as a measure of observer agreement, a proportion of agreeing readings (%) was accepted; in addition, the kappa index of agreement was calculated. RESULTS: Better agreement among three observers was attained when planar images were read in contrast to SPECT (I and II) results. The reading of SPECT II images yielded a higher frequency of diagnosed pathology (scars) in kidneys and is characterized by better overall agreement in detection by individual observers than a similar evaluation of SPECT I images. The Goldraich scale secures better interobserver agreement of renal scar detection than is seen when the Howard scale was applied to acquire the rating. CONCLUSIONS: The conclusion may be drawn that kidney scintigraphy is a method still burdened with a substantial subjectivism. Planar scintigraphy should be treated as a basic option for imaging post-inflammatory changes in kidneys.

[Iatrogenic hyperlipidemia after l-asparaginase and glucocorticoid treatment in two children with acute lymphoblastic leukemia]. / Jatrogenna hiperlipidemia w przebiegu leczenia L-asparaginaza i glikokortykosteroidami u dwojga dzieci z ostra bialaczka limfoblastyczna.

L-asparaginase and glucocorticosteroides are the main drugs used in the first-line treatment in children with acute lymphoblastic leukaemia. One of the observed side effects in the increase of serum level of triglycerides is synergistic manner. The paper describes two children with acute lymphoblastic leukaemia. In these patients we could observe remarkable hypertriglyceridemia, and hypercholesterolaemia with the increase of LDL-cholesterol after applying high doses of L-asparaginase and glucocorticosteroids simultaneously. The above-mentioned disorders were transient. In the analysis of the possible reasons of this pathology we took into consideration family predispositions, the transient deficit of lipoprotein lipase induced by L-asparaginase, improper diet and hyperthyroidismus.

[The influence of systemic blood pressure on renal function in children and adolescents with type 1 diabetes mellitus]. / Wplyw cisnienia tetniczego na funkcje nerek u dzieci i mlodziezy chorych na cukrzyce typu 1.

Elevated systemic blood pressure is one of the most important risk factor of diabetic nephropathy. The aim of the study was to estimate the influence of systemic blood pressure on renal function in children and adolescents with type 1 diabetes mellitus. Fifty-nine patients without evidence of arterial hypertension were recruited. In all patients 24-hour automatic blood pressure monitoring and renal examination (GFR, ERPF, FF, renoscintigraphy, urinary albumin excretion) were performed. The patients were divided into three groups according to blood pressure load: group I (less than 40% of systolic blood pressure--SBP and diastolic blood pressure--DBP values above 90th percentile for sex, age, height and body weight)--26 persons, group II (more than 40% DBP above 90th percentile)--25 persons, group III (more than. 40% SBP and DBP above 90th percentile)--8 persons. The study suggests that 24-hour automatic blood pressure monitoring is useful for early detection of increased blood pressure in diabetic children and adolescents. The patients with elevated both systolic and diastolic blood pressures had more frequently glomerular hyperfiltration. The persons with elevated only diastolic blood pressure had the lowest glomerular filtration and filtration fraction.

[ACE gene polymorphism and renal scarring in children with urinary tract infection and vesicoureteric reflux: preliminary results]. / Polimorfizm genu konwertazy angiotensyny a powstawanie blizn w nerkach u dzieci z zakazeniami ukladu moczowego w przebiegu odplywu pecherzowo-moczowodowego--doniesienie wstepne.

To investigate angiotensin-converting enzyme (ACE) gene deletion/insertion (D/I) polymorphism as a risk factor of renal scarring in children, we determined ACE genotypes in 63 paediatric patients with primary vesicoureteric reflux (VUR) grade I-V and recurrent urinary tract infections (UTI). Renal cortical scars were evaluated applying Technetium-99-m-unithiol SPECT method in 21 children. No statistically significant differences were found in allele and genotype distribution of the D/I polymorphism within ACE gene between children with VUR/UTI and healthy Caucasians (n = 806, after meta-analysis of literature data) (D allele frequencies--47% vs 54%, respectively). It suggests that ACE gene polymorphism is not associated with primary VUR. Renal scarring was revealed in 7 out of 21 children and there was also no statistically significant difference in D/I distribution between scar (n = 7) and non-scar (n = 14) subgroups of patients and controls. However, higher incidence of D allele (64%) in children with renal parenchymal damage could suggest the hypothesis that this genetic factor plays an important role in renal scarring. Therefore, to verify this assumption further studies on a larger group of patients are needed.