The interplay of oxidative stress and immune dysfunction in Hashimoto's thyroiditis and polycystic ovary syndrome: a comprehensive review.

In recent years, there has been a significant increase in the concomitant incidence of Hashimoto's thyroiditis (HT) and polycystic ovary syndrome (PCOS), both in terms of incidence, etiology, and clinical consequences. PCOS patients suffering from autoimmune thyroid diseases show insulin resistance, impaired glucose tolerance, weight gain, and metabolic and reproductive complications. Studies have shown that chronic stress and its consequence, i.e. oxidative stress, play an important role in the pathomechanism of both disorders. It has also been shown that long-term exposure to stress triggers biological mechanisms, in particular related to the regulation of the inflammatory cascade, which plays a key role in autoimmune diseases. The paper is a review of the literature on the role of chronic stress, oxidative stress, and immune processes in the pathogenesis of HT and PCOS. In addition, the review is a source of knowledge about the treatment of these diseases, and in particular the use of antioxidants in therapeutic management.

The Impact of Digital Screen Time on Dietary Habits and Physical Activity in Children and Adolescents.

Background: Over the last few decades, the time children spend using electronic devices has increased significantly. The aim of the study was to evaluate the impact of screen time on dietary behaviors and physical activity in children and adolescents. Methods: An online survey was conducted among parents of preschool and school-aged children during the COVID-19 lockdown in Poland. There were 3127 surveys used in the analysis. Results: Survey responses referred to 1662 (53%) boys and 1465 (47%) girls, with a mean age of 12.1 ± 3.4 years. During a routine weekday, most children (71%) spent >4 h on educational activities using electronic devices, and 43% of children spent 1−2 h using devices for recreational purposes. The majority of children (89%) were exposed to screens during meals, and ate snacks between main meals (77%). There was an association between screen time and the exposure to screens during meals, and between screen time and time spent performing physical activity. Conclusions: This study revealed that the majority of children were exposed to screens during meals, which is a risk factor of obesity. The promotion of the judicious use of digital devices and healthy dietary habits associated with the use of screens may be an important component of obesity prevention strategies.

Interleukin 6: Biological significance and role in inflammatory bowel diseases.

Cytokines affect a number of processes in the living body. Interleukin 6 (IL-6) is a cytokine involved in inflammation, infection response and also regulation of metabolism. It stimulates target cells through a membrane-bound IL-6 receptor. Inflammatory bowel diseases (IBD) are autoimmune diseases whose incidence and prevalence are increasing worldwide. It is a group of chronic gastrointestinal disorders characterized by multifactorial, still unknown pathogenesis, varied symptomatology, course with periods of exacerbation and remission, and polymorphic infiltration in histopathological examination. As it is known, pro-inflammatory cytokines, including IL-6, in IBD initiate, intensify and support the development of the inflammatory process in the intestine. Our knowledge of IL-6 biology has important consequences for therapeutic strategies. Elevation of IL-6 concentration can be considered as an early and sensitive, although non-specific marker for various inflammatory conditions and may be used in the diagnosis and monitoring of patients with IBD.

Interleukin 10 and interleukin 10 receptor in paediatric inflammatory bowel disease: from bench to bedside lesson.

BACKGROUND: The differences between adults and children in inflammatory bowel disease (IBD) phenotype, severity, complications, co-morbidities, and response to the therapy resulted in the extraction of paediatric IBD. It has been revealed that the substantial role in the development of IBD in children under 6 years of age plays a single genetic mutation (monogenic IBD). On the other hand, in older children and adolescents IBD is usually associated with number of interactions between susceptibility loci (polygenic IBD). MAIN BODY: Until now there have been described about 60 monogenic defects which affect the variety of immune mechanisms in IBD pathogenesis including epithelial barrier, function of neutrophil granulocytes and phagocytes, T- and B-cell selection and activation, immune inhibitory mechanisms, or apoptosis. Il-10 is an anti-inflammatory cytokine which modulates innate and adaptive immunity affecting expression of pro-inflammatory molecules and function of the variety of immune cells. Patients with identified defects in Il-10 pathway manifest with life-threating colitis with perianal lesions which occurs within first months of life. Allogenic hematopoietic stem cell transplantation is curative therapy in children with Il-10 signalling defects. CONCLUSION: Clinical awareness of Il-10 signalling defects enables early recognition and prompt management of the disease.

Biomarkers and Hematological Indices in the Diagnosis of Iron Deficiency in Children with Inflammatory Bowel Disease.

Inflammation may affect many routinely available parameters of iron homeostasis. Thus, the recognition of iron deficiency in inflammatory bowel disease (IBD) remains a diagnostic challenge in a clinical routine. The aim of the study was to detect the most efficient marker of iron deficiency in IBD children. In a group of 75 IBD children, we evaluated the sensitivity, specificity, accuracy, and positive and negative predictive values of erythrocytes' indices, including MCV, MCH, MCHC and RDW, and biochemical markers, including iron, transferrin, sTfR and sTfR/log ferritin, for identifying iron deficiency. Receiver operating characteristic (ROC) analysis was used to compare the ability of these parameters to detect iron deficiency. The best predictors of iron deficiency were sTfR/log ferritin, with accuracy 0.86, sensitivity 0.98, specificity 0.63, positive predictive value 0.83 and negative predictive value 0.94, and sTfR, with accuracy 0.77, sensitivity 0.82, specificity 0.67, positive predictive value 0.82 and negative predictive value 0.67. Moreover, sTfR/log ferritin exhibited the largest area under ROC (0.922), followed by sTfR (0.755) and MCH (0.720). The sTfR/log ferritin index appears to be the most efficient marker of iron depletion in pediatric IBD, and it may give an added value in the management of IBD patients.

Soluble transferrin receptor and soluble transferrin receptor/log ferritin index in diagnosis of iron deficiency anemia in pediatric inflammatory bowel disease.

BACKGROUND: There is no single reliable marker of iron homeostasis in inflammatory bowel disease. AIMS: To determine diagnostic usefulness of soluble transferrin receptor and soluble transferrin receptor/log ferritin index in iron deficiency anemia in children with inflammatory bowel disease. METHODS: We assessed soluble transferrin receptor in serum and calculated soluble transferrin receptor/log ferritin index in 75 children with inflammatory bowel disease. Diagnostic ability to identify iron deficiency anemia was examined by receiver operating characteristic analysis. RESULTS: Study group comprised 27 cases of iron deficiency anemia, 6 anemia of chronic disease with iron deficiency, 5 anemia of chronic disease. Soluble transferrin receptor was significantly increased in children with iron deficiency anemia (median: 1.63 µg/ml) compared to non-anemic children (median: 1.02 µg/ml). Soluble transferrin receptor/log ferritin index was significantly higher in iron deficiency anemia (median: 1.76) than in anemia of chronic disease (median: 0.55), anemia of chronic disease with iron deficiency (median: 0.68) or patients without anemia (median: 0.72). Soluble transferrin receptor and its index were not correlated with disease activity or inflammatory markers. Diagnostic power for soluble transferrin receptor/log ferritin index (0.864) was superior to soluble transferrin receptor (0.768) in iron deficiency anemia recognition. CONCLUSION: Soluble transferrin receptor/log ferritin index has better diagnostic utility than soluble transferrin receptor for iron deficiency anemia detection in pediatric inflammatory bowel disease.

Serum Hepcidin in Children with Inflammatory Bowel Disease.

BACKGROUND: Hepcidin is a major regulator of iron homeostasis and a mediator of innate immunity. To date, the role of hepcidin in inflammatory bowel disease (IBD) children is not clearly established. We aimed to assess serum hepcidin concentration in IBD children and correlate hepcidin with iron status parameters and inflammatory markers. METHODS: The study group included 46 pediatric patients with ulcerative colitis and 29 with Crohn's disease. In control group, there were 21 children with functional gastrointestinal disorders. The complete blood count, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, iron, ferritin, transferrin, hepcidin, soluble transferrin receptor, transferrin saturation, and interleukin-6 were measured. The study was approved by the local bioethical committee (KE-0254/22/2013). RESULTS: Mean serum hepcidin concentration was significantly decreased in IBD children (5.98 ng/mL) compared with controls (10 ng/mL) (P = 0.03). Hepcidin did not differ significantly between patients with Crohn's disease (6.9 ± 4.5 ng/mL) and ulcerative colitis (5.4 ± 5.3 ng/mL) (P = 0.07). Hepcidin was significantly decreased in IBD children with iron deficiency (4.9 ± 3.2 ng/mL) compared with healthy controls (10.5 ± 10 ng/mL) (P = 0.02). In anemic children with IBD, serum hepcidin (5.3 ± 4.4 ng/mL) was significantly reduced compared with healthy controls (10.5 ± 10 ng/mL) (P = 0.04), but comparable to nonanemic IBD children (6.6 ± 5.6 ng/mL) (P = 0.62). In IBD, children hepcidin was correlated solely with ferritin (P = 0.007; R = 0.3). CONCLUSIONS: In our study, serum hepcidin concentration was significantly decreased in IBD children compared with controls. Hepcidin correlated positively with ferritin, but not with any of inflammatory markers. It may suggest that in our cohort, hepcidin was regulated predominantly by iron storage level.

Closure of the thoracic duct from the left-side access: A case report.

BACKGROUND: We report a 16-year-old patient with a massive left-sided chylothorax after chemotherapy due to mixed germinal tumor of the testis with massive metastases located in the retroperitoneal space and posterior mediastinum. Chemotherapy resolved the metastases in the mediastinum but evoked a huge pleural effusion in the left pleural cavity, requiring surgical intervention.Left-sided access was used. The 5-mm camera and 3 5-mm working ports were inserted. The parietal pleura was incised and the esophagus located and protected. Behind the esophagus, the thoracic duct and concomitant tissue were clipped with titanium clips, and additionally, thrombin glue was used. Stopping of the lymph leakage was observed during surgery. A local argon pleurodesis was used to finish the procedure. The thoracic tube was removed on the third postoperative day. CONCLUSION: Left-side access may be a good alternative in the left-sided chylothorax, but the crucial points are location and protection of the esophagus during the procedure, which is also the landmark that allows for locating the thoracic duct.

Inflammatory and Lipid-Associated Markers of Cardiovascular Diseases in Children with First Exacerbation of Inflammatory Bowel Disease.

BACKGROUND Adult patients with inflammatory bowel disease (IBD) are at increased risk of early atherosclerosis and atherosclerosis-driven cardiovascular diseases. However, data on the development of early, subclinical atherosclerosis in children with IBD are scarce. The aim of this study was to assess selected biomarkers of atherosclerosis in children with IBD. MATERIAL AND METHODS The study group comprised 30 children with first exacerbation of IBD. Twenty healthy children were enrolled into the control group. Total cholesterol, triglycerides, low-density lipoproteins (LDL), high-density lipoproteins (HDL), lipoprotein (a) (Lp(a)), interleukin 6 (Il-6), high sensitivity C-reactive protein (hs-CRP), and oxidized LDL (ox LDL) were determined. RESULTS There were no significant differences in lipids profiles in IBD children and controls. Mean IL-6 level (8.996 pg/ml) was significantly higher in the IBD group compared to controls (3.502 pg/ml). Mean hs-CRP concentration was significantly higher in IBD children than in controls (7.648 and 1.290 µg/ml, respectively). In the IBD group, mean ox-LDL concentration (144.837 ng/ml) was lower than in controls (162.352 ng/ml), but the difference was non-significant (P=0.4). Mean Lp(a) serum level was higher in patients with IBD (19.418 mg/dl) than in controls (10.970 mg/dl), but it was also non-significant. CONCLUSIONS No significant differences were found in biomarkers of atherosclerosis in children with IBD compared to controls. Elevated IL-6 and hs-CRP level are well-established inflammatory markers. Further studies are needed to fully determine cardiovascular risk factors in IBD children.

Fitting the pieces of the puzzle together: a case report of the Dunnigan-type of familial partial lipodystrophy in the adolescent girl.

BACKGROUND: Familial partial lipodystrophy of the Dunnigan type (FPLD 2) is a rare autosomal dominant disorder caused by the mutations of the lamin A/C gene leading to the defective adipogenesis, premature death of adipocytes and lipotoxicity. FPLD 2 is characterized by a progressive loss of subcutaneous adipose tissue in the limbs and trunk, and accumulation of body fat in the face and neck with accompanying severe metabolic derangements including insulin resistance, glucose intolerance, diabetes, dyslipidemia, steatohepatitis. Clinical presentation of FPLD 2 can often lead to misdiagnosis with metabolic syndrome, type 2 diabetes or Cushing syndrome. CASE PRESENTATION: We report a case of a 14-year-old girl admitted to the Department of Paediatrics due to chronic hypertransaminasemia. On physical examination the girl appeared to have athletic posture. She demonstrated the absence of subcutaneous adipose tissue in the extremities, sparing the face, neck and gluteal area, pseudo-hypertrophy of calves, prominent peripheral veins of limbs, massive acanthosis nigricans around the neck, in axillary and inguinal regions and natural skin folds, hepatosplenomegaly. Laboratory results revealed hypertransaminasemia, elevated γ-glutamyltranspeptydase, and dyslipidemia, hyperinsulinaemia with insulin resistance, impaired glucose tolerance, and hyperuricemia. Diffuse steatoheptitis in the liver biopsy was stated. Clinical suspicion of FPLD 2 was confirmed genetically. The pathogenic mutation, R482W (p.Arg482Trp), responsible for the FPLD 2 phenotype was identified in one allele of the LMNA gene. CONCLUSIONS: Presented case highlights the importance of the holistic approach to a patient and the need of accomplished collaboration between paediatricians and geneticists. FPLD 2 should be considered in the differential diagnosis of diabetes, dyslipidemia, steatohepatitis, acanthosis nigricans and polycystic ovary syndrome.

[Coexistence of coeliac disease and inflammatory bowel disease in children]. / Wspólwystepowanie celiakii i nieswoistych zapalen jelit u dzieci.

Coeliac disease and inflammatory bowel disease are chronic inflammatory conditions of gastrointestinal tract with complex aetiology with genetic, environmental and immunological factors contributing to its pathogenesis. It was noted that immune-mediated disorders often coexist. There is well-known association between coeliac disease and type 1 diabetes and ulcerative colitis and primary sclerosing cholangitis. However, growing body of literature suggests the association between coeliac disease and inflammatory bowel disease, particularly ulcerative colitis. This is an extremely rare problem in paediatric gastroenterology. To date there have been reported several cases of children with coexisting coeliac disease and inflammatory bowel disease. Herewith we present review of current literature on coexistence of coeliac disease and inflammatory bowel disease in children.

Accumulation of CD5+CD19+ B lymphocytes expressing PD-1 and PD-1L in hypertrophied pharyngeal tonsils.

Programmed death-1 (PD-1) is one of the most important inhibitory co-receptors expressed predominantly on activated T and B lymphocytes whose expression could be sustained by permanent antigenic stimulation accompanying chronic or recurrent tonsillitis. The expression of PD-1 and PD-1L was analyzed using flow cytometry on hypertrophied tonsils collected from 57 children. We observed high expression of PD-1 and PD-1L on certain lymphocytes subpopulations of hypertrophied tonsils; among T cells, the expression of PD-1 on protein level was higher on CD4+ cells (70.3 %) than on CD8+ cells (35 %). Interestingly, a limited expression of PD-1 was observed on CD19+ B lymphocytes (6.5 %), while CD5+CD19+ B cells overexpressed PD-1 (52.5 %). Moreover, the expression of PD-1L was also higher on CD5+CD19+ B cells (16.5 %) than on CD19+ B cells (3.5 %) and on CD4+ T cells (20 %) than on CD8+ T cells (10 %). PD-1 and PD-1L expressions correlated only on CD5+CD19+ cells. In conclusion, high expression of PD-1 and PD-1L on T and B cells could represent hallmark of immune system adaptation to chronic antigenic exposition in patients with tonsillitis.

Esophageal Duplication Cyst Treated Thoracoscopically During the Neonatal Period: Clinical Case Report.

Esophageal duplication cysts (EDCs) are rare developmental anomalies. They may occur anywhere along the esophagus with the predominant location in the thoracic segment. Presently, most are diagnosed prenatally or in early childhood. The prevalence of EDCs is estimated at 1 in 8200 live births. Usually, cysts are asymptomatic in the neonatal period, but they may cause respiratory distress or feeding difficulties depending on the size and location of the lesion.This report presents a female neonate with a cyst located in the right pleural cavity recognized prenatally. Computed tomography confirmed the diagnosis and revealed a round cystic mass in proximity to the left lung base. Thoracoscopic cyst excision was undertaken on day 15 after delivery. The postoperative period was uneventful. Histological cyst examination confirmed the diagnosis of foregut duplication.This case underlines the importance of early diagnosis and treatment of EDC, before symptoms and complications arise, and confirms that surgery in the neonatal period is safe and effective.

[The role of hepcidin in iron metabolism in inflammatory bowel diseases]. / Rola hepcydyny w metabolizmie zelaza w przebiegu nieswoistych zapalen jelit.

Hepcidin is a 25-amino-acid peptide synthesized predominantly in hepatocytes, which plays an essential role in the regulation of systemic iron homeostasis. As a result of inflammation, hepcidin binds to ferroportin resulting in its internalization and degradation in enterocytes and macrophages. Thus iron is trapped in both enterocytes and macrophages, leading to functional hypoferremia. In iron deficiency or enhanced erythropoiesis, hepcidin expression is reduced. That fact results in increase of iron absorption and releasing iron storage from macrophages. The discovery of the biological properties of hepcidin clarified the relationship between iron homeostasis, immune response, and anaemia of chronic disease. Anaemia is the most common extra intestinal manifestation of inflammatory bowel disease. Anaemia significantly reduces the quality-of-life among patients and can lead to a number of serious complications, even life-threatening. The main types of anaemia in inflammatory bowel diseases are iron deficiency anaemia and anaemia of chronic disease. These two types of anaemia coexist commonly. The key issue is differentiation these types of anaemia to implement a proper management. Commonly used parameters as iron concentration, ferritin and transferrin, are rather unreliable indices for the evaluation of anaemia in inflammatory bowel diseases. In recent studies the important role of hepcidin as a potential alternative marker of anemia and iron status has been shown. Moreover, there are data that antihepcidin treatment may be an effective treatment of anaemia of chronic disease in inflammatory bowel disease. This paper presents hepcidin structure, mechanism of action and regulation, and highlights hepcidin function in anaemia in inflammatory bowel disease.