Time domain parameters of heart rate variability in children born as small-for-gestational age.

According to metabolic programming theory, small-for-gestational age patients are at high risk of cardiovascular diseases also because of the possible malfunction of the autonomic nervous system. Autonomic disorders can be assessed by heart rate variability. The aims of this study were to compare time domain parameters of heart rate variability in children born as small-for-gestational age and appropriate-for-gestational age and to assess the correlation of the postnatal and current somatic parameters with the time domain parameters. The small-for-gestational age group consisted of 68 children aged 5-10 years who were born with birth weight below the 10th percentile. The appropriate-for-gestational age group consisted of 30 healthy peers, matched in terms of gender and age. On the basis of Holter monitoring, slightly higher average heart rate was observed in the small-for-gestational age group than in the appropriate-for-gestational age group. It was found that all the time domain parameters (SDNN, SDNNi, SDANNi, rMSSD, pNN50) were lower in the small-for-gestational age group than in the appropriate-for-gestational age group. In the small-for-gestational age group, girls had lower heart rate and some of the heart rate variability parameters (SDNN, SDNNi, SDANNi) in comparison with boys. Children born as small-for-gestational age have impaired function of the autonomic nervous system. Moreover, in the small-for-gestational age group, autonomic balance moved towards the sympathetic component, which was evidenced by higher heart rate. Children with faster heart rate and lower heart rate variability parameters may be at risk of cardiovascular disease.

Influence of biologic therapy on growth in children with chronic inflammatory connective tissue diseases.

OBJECTIVES: Connective tissue diseases (CTD) are a heterogeneous group of chronic inflammatory conditions. One of their complications in children is the inhibition of growth velocity. Due to direct inflammation within the musculoskeletal system as well as glucocorticoid therapy, this feature is the most essential and is mainly expressed in the course of juvenile spondyloarthropathies and juvenile idiopathic arthritis (JIA). Duration of the disease, but predominantly the activity of the inflammatory process, seems to have a significant impact on the abnormal growth profile in children. Effective biological therapy leads to improvement of the patient's clinical condition and also, through the extinction of disease activity and reduction of daily doses of glucocorticosteroids (GCS), it gradually accelerates and normalizes the growth rate in children with CTD. Our objective was to evaluate the impact of biological therapy on growth in children with chronic inflammatory CTD. MATERIAL AND METHODS: Data from 24 patients with CTD treated with tumor necrosis factor-α-blockers (etanercept, adalimumab, golimumab) and an interleukin-6 receptor blocker (tocilizumab) were reviewed at the time of disease onset, biological treatment initiation and at least 12 up to 24 months onwards. The rate of growth was correlated with the daily doses of GCS, and the type and duration of biological therapy. RESULTS: Patient median height, measured as the change in height standard deviation score, was 0.36 ±1.07 at disease onset and -0.13 ±1.02 at biologic therapy initiation. The growth velocity accelerated in 17 patients (70.1%) during the biological treatment. Mean height-SDS improvement between biological treatment initiation up to two years was 0.51 ±0.58. In 47% of patients daily doses of GCS were reduced to 0 mg/kg/day. CONCLUSIONS: In the treatment of CTD, biological agents restore growth velocity not only by inflammation inhibition, but also through limiting GCS daily doses.

Imbalance of Th17 and T-regulatory cells in peripheral blood and synovial fluid in treatment naïve children with juvenile idiopathic arthritis.

OBJECTIVES: The imbalance between Th17 and T regulatory cells (Tregs) may be a key event in development of autoimmunity. The problem is poorly explored in juvenile idiopathic arthritis (JIA) so far. In this study, peripheral blood (PB) and synovial fluid (SF) Tregs and Th17 cells from were assessed in untreated JIA children. MATERIAL AND METHODS: In 50 children with JIA the PB or SF percentages of Tregs and Th17 cells were assessed by flow cytometry, in comparison with PB Tregs and Th17 cells from 28 healthy controls. Additionally, in both groups the levels of proinfammatory cytokines, such as interleukin (IL)-1ß, IL -6, IL -17, IL -21, IL -23 and tumor necrosis factor α (TN F-α) were assessed using ELI SA method. RESULTS: The proportion of JIA PB Th17 cells was significantly higher than in the controls (p = 0.01). Serum levels of IL -1ß, IL -6, IL -17, IL -23 were also significantly higher in JIA (p = 0.011, p = 0.007, p = 0.008 and p = 0.023, respectively). The highest serum IL -6 levels were observed in oligoarthritis JIA (p = 0.031). Synovial fluid IL -21 concentration was distinctly higher in polyarticular JIA. Synovial fluid levels of TN F-α, IL -1ß and IL -6 were significantly higher than in JIA PB (p = 0.038, p = 0.013 and p < 0.001, respectively). There was a significant correlation between IL -6 and PB Tregs (p = 0.02). CONCLUSIONS: The results of this comprehensive analysis indicate a role of Th17 cell activation in the pathogenesis of JIA.

Mixed connective tissue disease presenting with progressive scleroderma symptoms in a 10-year-old girl.

Mixed connective tissue disease (MCTD) is a systemic inflammatory disease affecting connective tissue with the underlying autoimmunological mechanism. The core of MCTD is an appearance of symptoms of several other inflammatory diseases of connective tissue - systemic lupus erythematosus, systemic scleroderma, poly- or dermatomyositis, rheumatoid arthritis at the same time, accompanied by a high level of anti-ribonucleoprotein antibodies (anti-U1RNP). The disease was described more than 40 years ago by Sharp et al. During recent years, many efforts to better understand clinical and serological features of MCTD have been made. Diagnosis of MCTD can be difficult. Obligatory international diagnostic criteria are required to be fulfilled. Several versions of such criteria have been proposed, but the most widely used one was described by Kasukawa. There is no consensus about treatment - a choice of drugs depends on symptoms. We present a case of a 10-year-old girl with sclerodactyly and trophic damages of fingers accompanied by symptoms of Raynaud's phenomenon. After an almost 2-year course of the disease, a diagnosis of MCTD has been established.

Why and How Should We Assess the Cardiovascular Risk in Patients with Juvenile Idiopathic Arthritis? A Single-Centre Experience with Carotid Intima-Media Measurements.

BACKGROUND: Children diagnosed with juvenile idiopathic arthritis (JIA) are thought to be more likely to develop cardiovascular disease in adulthood. The factors modulating the cardiovascular risk, involving exposure to secondhand smoking, sedentary lifestyle and abnormal body mass index, might have had a stronger impact during the COVID-19 pandemic. The lack of reliable prognostic markers for a higher probability of cardiovascular events might be solved by carotid intima-media thickness (cIMT) measurement. The paramount goal of the study was to assess its usefulness in JIA patients. MATERIALS AND METHODS: The results of cIMT measured by a single physician in 45 children diagnosed with JIA were compared to 37 age- and sex-matched healthy counterparts. The analysis also involved anthropometric parameters, laboratory tests, and a survey regarding lifestyle-related factors. RESULTS: Four JIA patients appeared to have cIMT above the 94th percentile. A positive correlation between erythrocytes sedimentation rate (ESR) and right carotid artery percentiles was found. Passive smoking increased the cardiovascular risk regardless of JIA. Doubling the daily screen time during the pandemic led to a significant reduction in children's physical activity. However, the number of enrolled subjects was not enough to make significant recommendations. CONCLUSIONS: cIMT measurements remain an interesting perspective for future cardiovascular screening of children with JIA. It has yet to be determined whether it should be considered in all JIA patients on a reliable basis.

Assessment of Cardiovascular Risk Factors in Patients with Juvenile Idiopathic Arthritis.

INTRODUCTION: The aim of this study was to assess the exposure to cardiovascular disease (CVD) risk factors in patients with juvenile idiopathic arthritis (JIA). Intima-media complex thickness (IMT), selected metabolic parameters and health behaviors were assessed in the course of the study. METHODS: The study included study group, which consisted of 45 patients with JIA and 37 healthy age- and sex-matched children in the control group. Analyses in both groups included anthropometric parameters, laboratory tests, IMT and a questionnaire on exposure to modifiable CVD risk factors. RESULTS: The study confirmed that CVD risk factors were present in both groups of patients. Significantly more children with JIA had abnormal BMI (p = 0.006) compared to the control group. Children in the study group were more likely to consume fruit regularly (p = 0.021) and less likely to consume fast food (p = 0.011) and sweetened beverages (p = 0.042) than children in the control group. Only 1 patient with JIA met criteria for ideal cardiovascular health. Dietary habits were not associated with IMT values, BMI, presence of joint pain or biochemical parameters in the study group. CONCLUSIONS: Patients with JIA are exposed to cardiovascular risk factors equally to their healthy peers. Ideal cardiovascular health should be pursued in the pediatric population with particular attention paid to patients with chronic diseases (i.e., JIA). The application of carotid artery IMT measurement in the assessment of CVD risk requires studies on a larger group of patients.

Takayasu's arteritis mimicking Kawasaki disease in 7-month-old infant, successfully treated with glucocorticosteroids and intravenous immunoglobulins.

Takayasu's arteritis (TA) rarely occurs in infants. There are only four reports on TA in children below 1 year of age, revealing diversity of its symptoms. We describe a 7-month-old female infant hospitalized for hectic fever, irritability, high acute phase indices, and coronary artery dilatations found on echocardiography, which suggested Kawasaki disease (KD). Despite of standard treatment, rapid development of thoracic and abdominal aorta aneurysms occurred, while coronary artery abnormalities regressed. The initial diagnosis was changed for TA. Subsequently implemented glucocorticosteroids led to clinical and laboratory normalization. However, 2 months after treatment discontinuation, TA relapsed. Glucocorticosteroid therapy was restarted with additional introduction of intravenous immunoglobulins (IVIG), resulting in full and stable remission lasting over 1 year. Thus, diagnosis and treatment of infant TA pose a big challenge to physicians. TA onset in infants may mimics KD. Prolonged glucocorticosteroids and IVIG administration can be recommended in the youngest patients with TA.

Association of c.802C>T polymorphism of NOD2/CARD15 gene with the chronic gastritis and predisposition to cancer in H. pylori infected patients.

This paper shows analysis of the association of the 802C>T polymorphism of the NOD2/CARD15 gene with the occurrence of the chronic inflammation of the gastric mucosa associated with the Helicobacter pylori infections, development of intestinal metaplasia and dysplasia and, in the result of this, gastric cancer. Genomic DNA samples were extracted from paraffin blocks of gastric mucosal biopsies and from peripheral blood. H. pylori infection was confirmed by histological analysis and urease test. Pyrosequencing of 802C>T polymorphism of the NOD2/CARD15 gene was performed for H. pylori infected patients (131) and population group (100). Analysis of the NOD2/CARD15 gene showed that frequency of the T allele was significantly higher (32.8%) in the group of patients in comparison with the population group (18.1%), with the relative risk of 1.8. In the patient group, the frequency of the CC genotype was 51.1%, CT 32.1% and TT 16.8% (relative risk: 0.7, 1.1 and 4.2, respectively), while in the population group it was 69.0%, 25.7% and 5.3% (relative risk: 1.0, 0.9 and 1.3, respectively). The increasing frequency of the T allele and CT and TT genotypes in the patients with increasingly deeper changes in the gastric mucosa becomes apparent. Our findings suggest that polymorphism 802C>T is associated with changes in gastric mucosa and plays a significant role in the initiation and the progression of carcinogenesis. The number of observed mutations in gastric mucosa correlated with severity of disease.

Prenatal diagnosis and follow-up of 23 cases of cardiac tumors.

OBJECTIVE: To evaluate the prenatal characteristics and postnatal outcome of cardiac tumors diagnosed at two prenatal Polish cardiology centers. METHODS: Descriptive analysis of 23 fetuses with cardiac tumors (12 multiple and 11 single) diagnosed over 16 years (from 1993 to 2009). Congestive heart failure was diagnosed when the cardiovascular profile score was seven or less. RESULTS: Associated structural congenital heart defects were present in three fetuses, extracardiac anomalies in three, and chromosomal anomalies in two. Congestive heart failure developed in five cases. Perinatal survival was not different between cases with and without cardiac failure (2/5 vs 12/18, p = 0.28). The main ultrasonographic signs observed prenatally in association with cardiac tumors were cardiomegaly, left ventricular outflow tract obstruction, pericardial effusion, and hypokinesis. A diagnosis of tuberous sclerosis was eventually made in all 12 fetuses with multiple tumors. Perinatal death occurred in 4/11 cases with single tumors and in 5/12 with multiple tumors (p = 0.57). Surgical resection of the tumor was performed in 3/11 neonates with single tumors (histopathologically: rhabdomyoma, teratoma, and fibroma) and in 2/12 with multiple tumors (both rhabdomyomas). CONCLUSIONS: Survival is not different between neonates with single and multiple tumors and between those with and without congestive heart failure.

DNA variants in Helicobacter pylori infected patients with chronic gastritis, dysplasia and gastric cancer.

PURPOSE: The main scope of this study was to evaluate the importance of selected DNA variants for developing inflammation of gastric mucosa and carcinogenesis in gastrointestinal diseases in patients infected with Helicobacter pylori. PATIENTS AND METHODS: Patients subjected to analysis constituted a group of 131 consecutive cases, with control groups consisting of 100 healthy volunteers and 13 dyspeptic patients. Molecular analysis included the following genes: TP53 (c.743 G > A, c.746 G > A, c.749C > T), MSH2 (c.942 + 3A > T), MLH1 (c.2041 G > A), NOD2/CARD15 (c.3016_3017insC, c.802C > T), IL1A (c.-949C > T) and IL1B (c.315C > T). DNA variants were detected using PCR-RFLP, pyrosequencing and sequencing. RESULTS: Mutations of the analyzed genes were observed more frequently in patients with a higher degree of mucosal lesions (50.9%) than in patients with milder mucosal changes (27.6%). Single mutations and polymorphisms did not affect the course of the disease. Our analysis confirms the influence of the NOD2/CARD15 c.802C > T polymorphism on the development of mucosal changes. A correlation of the frequency of the CT genotype of the NOD2/CARD15 c.802C > T polymorphism with the NOD2/CARD15 c.3016_3017insC mutation was observed. The TT genotype frequency in the c.315C > T IL1B gene polymorphism was statistically significantly higher in patients with mucosa changes. CONCLUSIONS: Accumulation of molecular abnormalities may increase the susceptibility to inflammatory response of the gastric mucosa in H. pylori-infected patients and play an important role in the development of chronic active gastritis, atrophy, intestinal metaplasia, dysplasia and the intestinal type of gastric cancer. The severity of gastric mucosal damage correlates with the presence of mutations in the gastric mucosa and the age of patients.

Relationship between impaired apoptosis of lymphocytes and distribution of dendritic cells in peripheral blood and synovial fluid of children with juvenile idiopathic arthritis.

INTRODUCTION: The pathogenesis of juvenile idiopathic arthritis (JIA) is not fully understood. Recently the present authors described disturbed apoptosis of JIA lymphocytes in both peripheral blood (PB) and synovial fluid (SF) as well as an abnormal distribution of blood dendritic cells (BDCs) between the PB and SF in this disease. Possible relationships between these events during the development of JIA process are assessed here. MATERIALS AND METHODS: Lymphocyte apoptosis and BDC counts were assessed in the PB and SF of untreated JIA children. Lymphocyte apoptosis was analyzed by the Annexin-V/propydium iodide assay. Total DC (TDC) number was based on the sum of three BDC subpopulations determined using a panel of monoclonal antibodies against BDC antigens (BDCA): myeloid type 1 (mDC1, BDCA-1(+)/HLA-DR(+)/CD19(-)), myeloid type 2 (mDC2, BDCA-3(+)/HLA-DR(+)/CD14(-)), and plasmacytoid (pDC, BDCA-2(+)/HLA-DR(+)/CD123(+)). Cells were enumerated by the flow cytometric "single-platform" method. The concentration of tumor necrosis factor (TNF)-alpha and the distribution of particular lymphocyte subtypes in both PB and SF were also investigated. RESULTS: There was significant positive correlation between apoptosis of PB lymphocytes and SF TDC count (p=0.002) as well as SF TNF-alpha concentration (p=0.007). SF TNF-alpha levels also correlated with SF TDC count (p=0.003). Moreover, JIA SF was distinctly enriched with CD4+ and CD8+ T lymphocytes and included CD4(+)/CD25(high) cells as well. There was significant positive correlation between the number of CD4(+)/CD25(high) cells and SF JIA BDC count (p=0.015). CONCLUSIONS: These data suggest a possible link between impaired apoptosis of PB/SF lymphocytes and increased recruitment of PB BDCs to SF and other elements of the immune system in JIA, including regulatory CD4+/CD25high cells.

Myocardial dysfunction in children with intrauterine growth restriction: an echocardiographic study.

INTRODUCTION: The prevalence of intrauterine growth restriction (IUGR) is about 3-10% of live-born newborns and can be as high as 20% in developing countries. It may result in the occurrence of cardiovascular diseases later in life. METHODS: The aim of this study was echocardiographic evaluation, with the use of conventional and tissue Doppler parameters, of cardiac function in children born with IUGR, and comparison with healthy peers born as normally grown foetuses. RESULTS: In the IUGR group, E wave and E/A ratio were significantly lower compared to the control group. A wave, isovolumetric relaxation time, deceleration time, myocardial performance index as well as E/E' septal and E/E' lateral indices were significantly higher compared to healthy peers. CONCLUSION: Children with IUGR presented with subclinical myocardial dysfunction.

Serum Angiogenesis Markers and Their Correlation with Ultrasound-Detected Synovitis in Juvenile Idiopathic Arthritis.

Synovial angiogenesis is considered to be an important early step in the pathogenesis of juvenile idiopathic arthritis (JIA). In this study we assessed levels of angiogenic markers in serum or synovial fluid and their possible relevance to disease activity or degree of ultrasound signs of synovial inflammation and angiogenesis in early JIA. The concentration of vascular endothelial growth factor (VEGF), its soluble receptors 1 and 2 (sVEGF-R1, sVEGF-R2), and angiopoietins 1 and 2 (ANG-1, ANG-2) were evaluated in 43 JIA patients and 23 healthy controls. Synovial angiogenesis was assessed by means of Power-Doppler Ultrasonography (PDUS), according to the fourth-grade vascularity scale. VEGF and its receptors' (sVEGF-R1, sVEGF-R2) serum levels were significantly higher in JIA patients (p = 0.002). We found large variation in serum ANG-1 and ANG-2 levels. The PDUS imaging identified increased synovial microvascular blood flow in 15 (35.7%) examined JIA children. Intensity of joint vascularization correlated with higher serum VEGF and its levels was lowest in grade 0 and highest in grade 3 (p < 0.007 and p < 0.001, resp.). In conclusion, the high correlation between synovial microvascular blood flow, serum angiogenic proteins, and symptoms of synovitis may indicate its important role in pathogenesis of JIA.

Myocardial dysfunction measured by tissue Doppler echocardiography in children with primary arterial hypertension.

BACKGROUND AND AIM: To evaluate myocardial function with the use of tissue Doppler echocardiography in children with primary hypertension. METHODS: A total of 64 subjects (34 with hypertension, 30 control) underwent echocardiographic evaluation of systolic and diastolic function with the use of standard and tissue Doppler echocardiography parameters. RESULTS: The left ventricular myocardial performance index was higher in children with hypertension (0.46 ± 0.08 vs. 0.35 ± 0.03; p < 0.01). The value of the A wave was higher in the hypertensive children group (0.59 ± 0.12 m/s vs. 0.49 ± 0.09 m/s; p < 0.01), while the E/A ratio was significantly lower in this group (1.58 ± 0.31 vs. 1.77 ± 0.28; p < 0.01). The values of isovolumetric relaxation time and deceleration time were significantly higher in patients with blood pressure elevation. The velocity of mitral flow propagation was lower (0.61 ± 0.08 m/s vs. 0.72 ± 0.10 m/s; p < 0.01) and E/Vp ratio was higher (1.50 ± 0.27 vs. 1.21 ± 0.23; p < 0.01) in hypertensive children. Evaluation of the left ventricle function with the use of tissue Doppler echocardiography showed significantly worse values of S' and E' septal, and S' and E' lateral in hypertensive children. The value of septal E'/A' ratio was lower in children with hypertension (1.52 ± 0.24 vs. 1.69 ± 0.25; p < 0.01), while the value of this index for lateral wall was similar. The values of E/E' septal and E/E' lateral were higher in patients with hypertension. CONCLUSIONS: In children with primary arterial hypertension, with the use of tissue Doppler echocardiography there are significantly lower values of diastolic and systolic parameters observed, which may be a sign of myocardial function deterioration.

Reactive oxygen species and serum antioxidant defense in juvenile idiopathic arthritis.

In autoimmune inflammatory diseases, including juvenile idiopathic arthritis (JIA), which leads to joint destruction, there is an imbalance between production of reactive oxygen species (ROS) and their neutralization which, as a consequence, leads to "oxidative stress." The aim of the study was to assess the concentration of oxidative stress markers: nitric oxide (NO), a degree of lipid membrane damage, and total antioxidant plasma capacity in children with JIA. Thirty-four children with JIA were included into the study. A degree of lipid membrane damage (lipid peroxidation products) was estimated as thiobarbituric acid-reactive substances (TBARs), NO concentration as NO end-products: nitrite/nitrate (NO2(-)/NO3(-)) and total antioxidant plasma capacity as ferric reducing ability of plasma (FRAP). NO2(-)/NO3(-) serum concentration in children with JIA was statistically significantly higher than that in healthy children (p = 0.00069). There was no significant difference in TBAR levels between children with JIA and the control group. FRAP in sera of children with JIA was lower than that in healthy children, but the difference was not statistically significant. A statistically significant positive correlation was observed between NO end products and the 27-joint juvenile arthritis disease activity score (JADAS-27) and ESR, and a negative correlation was observed between FRAP and C-reactive protein (CRP) and white blood cell count (WBC). Our results confirm the increased oxidative stress in children with JIA. Overproduction of NO and decrease in the antioxidant plasma capacity may be involved in JIA pathogenesis.

Atypical fibrous histiocytoma and atypical fibroxanthoma: presentation of two cases.

We report two rare examples of dermal fibrohistiocytic stromal tumors: one case of atypical fibrous histiocytoma (AFH) and another one of atypical fibroxanthoma (AFX), which can be confused in surgical pathology diagnosis with high-grade malignant neoplasm. Histologically, a proliferation of mononuclear, spindle-shaped, or histiocytoid cells and/or multinucleated cells, usually admixed with inflammatory cells was observed in both cases, but some clinicopathological differences allowed their distinction. Immunohistochemistry is of a little help in differential diagnosis between these two entities however, it is very useful in differentiating with other groups of tumors. Recognition of AFH and AFX is important, especially to prevent incorrect aggressive treatment in those cases that may be confused with high-grade sarcoma. Because of the potentially aggressive behavior in rare cases and the lack of clear-cut predictive morphologic patterns that would specify a poor clinical outcome, complete surgical excision in all cases is recommended.