Changes in serum hepcidin levels in children with inflammatory bowel disease during anti-inflammatory treatment.

AIM: The aim of this study was to compare changes in serum hepcidin levels in paediatric patients with inflammatory bowel disease during therapy and correlate them with markers of iron metabolism, inflammation and type of treatment. METHODS: Children with newly diagnosed Crohn's disease (CD) and ulcerative colitis (UC) were included in this longitudinal study. Blood and stool samples were collected to assess levels of serum hepcidin and markers of iron metabolism parameters and inflammation. The parameters were examined before treatment (baseline levels) and compared with levels in the follow-up period during maintenance therapy (mean follow-up of 39 months after diagnosis). RESULTS: Patients with CD (n = 30) had higher serum hepcidin levels (expressed as a median and interquartile range) at diagnosis than subjects with UC (n = 13). These levels significantly decreased during the follow-up (from 36.5 (11.5-79.6) to 2.1 (0.9-6.7) ng/mL). In contrast, no significant serum hepcidin level changes were observed in the UC patients (5.4 (3.4-16.6) vs. 4.8 (0.9-8.1) ng/mL). While hepcidin level changes correlated with disease activity and inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein), in CD patients, they correlated only with serum iron levels in patients with UC. Biological therapy was accompanied by a significant decrease in C-reactive protein and interleukin-6 compared to conventional anti-inflammatory therapy in CD patients. CONCLUSIONS: Children with CD had higher serum hepcidin levels on diagnosis compared to subjects with UC. During an anti-inflammatory therapy, serum hepcidin decreased in the CD group but remained consistently low in children with UC.

Prediction of Thiopurine Metabolite Levels Based on Haematological and Biochemical Parameters.

OBJECTIVES: Therapeutic drug monitoring of thiopurine erythrocyte levels is not available in all centers and it usually requires quite a long time to obtain the results. The aims of this study were to build a model predicting low levels of 6-thioguanine and 6-methylmercaptopurine in pediatric inflammatory bowel disease (IBD) patients and to build a model to predict nonadherence in patients treated with azathioprine (AZA). METHODS: The study consisted of 332 observations in 88 pediatric IBD patients. Low AZA dosing was defined as 6-thioguanine levels <125 pmol/8 × 10 erythrocytes and 6-methylmercaptopurine levels <5700 pmol/8 × 10 erythrocytes. Nonadherence was defined as undetectable levels of 6-thioguanine and 6-methylmercaptopurine <240 pmol/8 × 10 erythrocytes. Data were divided into training and testing part. To construct the model predicting low 6-thioguanine levels, nonadherence, and the level of 6-thioguanine, the modification of random forest method with cross-validation and resampling was used. RESULTS: The final models predicting low 6-thioguanine levels and nonadherence had area under the curve, 0.87 and 0.94; sensitivity, 0.81 and 0.82; specificity, 0.80 and 86; and distance, 0.31 and 0.21, respectively, when applied on the testing part of the dataset. When the final model for prediction of 6-thioguanine values was applied on testing dataset, a root-mean-square error of 110 was obtained. CONCLUSIONS: Using easily obtained laboratory parameters, we constructed a model with sufficient accuracy to predict patients with low 6-thioguanine levels and a model for prediction of AZA treatment nonadherence (web applications: https://hradskyo.shinyapps.io/6TG_prediction/ and https://hradskyo.shinyapps.io/Non_adherence/).

Hepcidin in newly diagnosed inflammatory bowel disease in children.

AIM: Hepcidin is a central regulator of iron homeostasis. Its production is also influenced by systemic inflammation. The aims of this study were to compare hepcidin levels in paediatric patients newly diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) and to determine the association of hepcidin levels with laboratory and clinical parameters of inflammatory bowel disease (IBD) activity. METHODS: Children with newly diagnosed IBD between January 2012 and September 2016 were enrolled in this comparative cross-sectional study. We analysed levels of serum hepcidin, C-reactive protein, iron, ferritin, soluble transferrin receptors, blood count and faecal calprotectin in all subjects. Serum hepcidin levels were measured by reverse-phase liquid chromatography. The Paediatric Crohn's Disease Activity Index was used to evaluate CD in children, and Paediatric Ulcerative Colitis Activity Index was used for the assessment of UC disease activity. RESULTS: Subjects with CD (n = 53) had significantly higher serum hepcidin levels compared with subjects with UC (n = 23) - 22.6 ng/mL (range 8.5-65.0) versus 6.5 ng/mL (range 2.4-25.8) (P < 0.05). Hepcidin was independently associated with ferritin levels in all IBD patients (P < 0.05). Moreover, there was a significant positive correlation between hepcidin and platelet count (P < 0.05) in children with CD and a negative correlation between hepcidin and faecal calprotectin (P < 0.05) in children with UC. CONCLUSION: Different hepcidin levels between children with newly diagnosed CD and UC suggest the distinct contribution of iron deficiency and/or systemic inflammation to anaemia and may help clinicians choose the best anti-anaemic treatment.

Bilateral position-related ulnar neuropathy at elbow in pediatric population and review of the literature.

Perioperative ulnar neuropathies attributed to inappropriate arm positioning and padding during surgical procedures are commonly found in adults. However, their extremely rare incidence in the pediatric population may cause absent awareness of the risk of nerve injury in anesthetized pediatric patients. Furthermore, young patients respond to conservative treatment of neuropathy less favorably than adults and their response also depends on the pathomechanism of the ulnar nerve injury. A surgeon's or anesthetist's failure to recognize all of these specifics in children may result in substantial morbidity of young patients leading to lawsuits. Fortunately, with an adequate knowledge of surgical anatomy and types of procedures and positions in which the ulnar nerve is particularly vulnerable, and familiarity with measures to minimize the potential for neuropathy, this serious complication can be prevented. The aims of this review are to highlight personal experience and current knowledge of the rare position-related ulnar neuropathy, both from a clinical and anatomical-pathophysiological perspective, and to raise awareness about this rare but serious complication in the pediatric population.

Measuring hope: Standardization of the Czech version of the Adult Dispositional Hope Scale in healthy adults.

OBJECTIVES: Hope is an important factor that influences mental state of individuals and efficacy of systematic and supportive psychotherapy. The goal of the study was to translate the Adult Dispositional Hope Scale (ADHS) to Czech, evaluate its psychometric properties and create norms to interpret the scale scores. METHODS: The scale consists of twelve items. Four items assess the ability of pathway thinking, four items measure agency, and the remaining four items are fillers that are not interpreted. There were 394 adult participants with negative psychiatric history who completed the ADHS and BDI-II. Their mean age was 27.1±11.7 years, most of them were women (n=303; 76.9%). RESULTS: There was no significant relationship between age or sex and hope. Reliability was analyzed by Cronbach alpha (α=0.82) and the split-half method (Spearman-Brown coefficient = 0.81). The factor structure of the scale was approved by the results of exploratory and confirmatory factor analysis, except the ninth item that similarly saturated both subscales. The ADHS moderately negatively correlated with BDI-II. Norms were created for the scores of the entire scale and both subscales. CONCLUSION: The Czech version of the Adult Dispositional Hope Scale shows adequate psychometric properties.

Unmet psychosocial needs in adolescents with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel diseases (IBD) are severe medical conditions with adverse impact on the quality of life of both children and their caregivers. IBD are associated with many limitations in personal and interpersonal functioning, and it also restricts the patients' ability to use the full potential (extent) of their capabilities. With the progress and humanization in society, the issue of patients' needs became an important topic; however, the psychosocial functioning and quality of life of adolescents suffering from IBD and their caregivers have been understudied. The aim of this article is to provide a comprehensive, up-to-date literature review of the unmet needs of patients with IBD and their caregivers. METHOD: A computerized search of MEDLINE publications from 1990 to 2016 using the keywords "inflammatory bowel disease", "Crohn disease", "ulcerative colitis" and "unmet needs". In the period 1990-2016, the MEDLINE searches identified 54 publications. Articles cited in the papers from these searches were also used. The total number of 132 particular articles were collected, sorted by their relevance and key articles (n=72) listed in reference lists were searched. RESULTS: Patients' needs differ at various stages of the illness and may have different origins and goals. Thus, we divided the needs into five groups according to their nature; i.e. needs to be connected with symptoms, treatment, quality of life, family and age-related challenges. We provide implications of the patients' needs for pharmacotherapy and psychotherapy. CONCLUSION: Following the needs of patients with IBD may be a crucial part of the therapeutic process. Due to the better understanding and cooperation, the impact of disease could be reduced, and the physical and mental condition of the patient could be improved. However, many needs remain unmet due to both medical and social factors.

Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and biological entity: a collaborative study by the International-Berlin-Frankfurt-Munster AML-study group.

In pediatric acute myeloid leukemia (AML), cytogenetic abnormalities are strong indicators of prognosis. Some recurrent cytogenetic abnormalities, such as t(8;16)(p11;p13), are so rare that collaborative studies are required to define their prognostic impact. We collected the clinical characteristics, morphology, and immunophenotypes of 62 pediatric AML patients with t(8;16)(p11;p13) from 18 countries participating in the International Berlin-Frankfurt-Münster (I-BFM) AML study group. We used the AML-BFM cohort diagnosed from 1995-2005 (n = 543) as a reference cohort. Median age of the pediatric t(8;16)(p11;p13) AML patients was significantly lower (1.2 years). The majority (97%) had M4-M5 French-American-British type, significantly different from the reference cohort. Erythrophagocytosis (70%), leukemia cutis (58%), and disseminated intravascular coagulation (39%) occurred frequently. Strikingly, spontaneous remissions occurred in 7 neonates with t(8;16)(p11;p13), of whom 3 remain in continuous remission. The 5-year overall survival of patients diagnosed after 1993 was 59%, similar to the reference cohort (P = .14). Gene expression profiles of t(8;16)(p11;p13) pediatric AML cases clustered close to, but distinct from, MLL-rearranged AML. Highly expressed genes included HOXA11, HOXA10, RET, PERP, and GGA2. In conclusion, pediatric t(8;16)(p11;p13) AML is a rare entity defined by a unique gene expression signature and distinct clinical features in whom spontaneous remissions occur in a subset of neonatal cases.

Heart rate variability in children with inflammatory bowel diseases.

OBJECTIVE: Heart rate variability (HRV) oscillations are used in the detection of autonomic instabilities in various clinical disorders. METHODS: We compared the HRV as a possible marker of chronic distress in children with inflammatory bowel disease (IBD) with HRV frequencies in the healthy controls. Participants were 29 children with IBD (19 Crohn's disease and 10 ulcerative colitis), 25 children were in remission and 4 presented mild disease activity. They were compared with the control group of 35 healthy children of the same age (13-16 years-old). RESULTS: In HRV assessment, adolescents with IBD had significantly lower levels of the spectral activity in an LF band in all three positions; lower levels of VLF in both supine positions; and the ratio of the spectral activity at LF/HF was significantly lower in the second post (standing). CONCLUSION: These results indicate children with IBD have less adaptability to stress.

Quality of life in adolescents with inflammatory bowel disease and their parents--comparison with healthy controls.

OBJECTIVE: Inflammatory bowel diseases (IBD) are chronic diseases with a significant impact on quality of life (QoL). The aim of the study was to examine the QoL in children with IBD and their families, depression and anxiety for both the children and their parents. METHODS: Participants were 29 adolescents with IBD (19 individuals suffered from the Crohn disease, another ten had ulcerative colitis) and 40 healthy controls of the same age (13-16 years). The probands and their parents completed questionnaires measuring the quality of life (KidScreen-10, PedsQL), depression (CDI, BDI-II), and anxiety (SAD, BAI). RESULTS: The QoL measured by questionnaires did not differ between the adolescent participants, but it was significantly lower in the parents of the children with IBD than in the parents of the healthy controls. The parents of the IBD children scored lower in the Family Impact Module Total Scale Score and the parental Health-Related QoL Summary Score. The fathers of the IBD children also had a lower level of the Family Functioning Summary Score. There wasn't any difference in the levels of anxiety and depressive symptoms among the IBD adolescents and the controls. CONCLUSIONS: The parents of the children with IBD experience lower QoL than the parents with the healthy children. The children with IBD show similar symptoms of depression, anxiety, and QoL as the healthy controls.

[The prospects for children with acute lymphoblastic leukemia of being cured has increased in the Czech Republic in the 21st century to 90% - outcome of the ALL-IC BFM 2002 trial]. / Sance na vylécení detí s akutní lymfoblastickou leukémií stoupla v Ceské republicev 21. století na 90 % - výsledky studie ALL IC-BFM 2002.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most frequent childhood malignancy. Treatment has been unified in the middle of 1980 in the Czech Republic. In 2002-2007 children and adolescents with acute lymphoblastic leukemia were treated in an international randomized trial ALL-IC BFM 2002 in the Czech Republic. 291 patients aged 1-18 years were enrolled; infants below 1 year entered a separate trial. METHODS AND RESULTS: Patients were stratified into three risk groups according to their age, initial leukocyte count, prednisone response, presence of fusion genes BCR/ABL or MLL/AF4, bone marrow D+15 and remission status D+33. The whole therapy took 24 months. Randomized late intensification compared standard BFM therapy with extended, usually more intensive experimental treatment. The median follow-up was 8.7 years. Complete remission was achieved in 97.9% patients, 1% died in remission. 11% of children relapsed, 1.7% with CNS involvement. Six children (2.1%) developed secondary malignancy. Event free survival (EFS) 8 years from diagnosis was 83.5%, overall survival (OS) 91.4%. EFS and OS of the risk groups were: standard risk: 89.4%; 98.1%; intermediate risk: 82.6%; 89.6%; high risk: 68.8%; 78.1%. Male sex and age above 10 years were adverse prognostic factors. CONCLUSIONS: In comparison with the previous trial ALL-BFM 95, significant improvement was achieved.

Minimal residual disease in peripheral blood at day 15 identifies a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with superior prognosis.

BACKGROUND: Most minimal residual disease-directed treatment interventions in current treatment protocols for acute lymphoblastic leukemia are based on bone marrow testing, which is a consequence of previous studies showing the superiority of bone marrow over peripheral blood as an investigational material. Those studies typically did not explore the prognostic impact of peripheral blood involvement and lacked samples from very early time points of induction. DESIGN AND METHODS: In this study, we employed real-time quantitative polymerase chain reaction analysis to examine minimal residual disease in 398 pairs of blood and bone marrow follow-up samples taken from 95 children with B-cell precursor acute lymphoblastic leukemia treated with the ALL IC-BFM 2002 protocol. RESULTS: We confirmed the previously published poor correlation between minimal residual disease in blood and marrow at early treatment time points, with levels in bone marrow being higher than in blood in most samples (median 7.9-fold, range 0.04-8,293-fold). A greater involvement of peripheral blood at diagnosis was associated with a higher white blood cell count at diagnosis (P=0.003) and with enlargement of the spleen (P=0.0004) and liver (P=0.05). At day 15, a level of minimal residual disease in blood lower than 10(-4) was associated with an excellent 5-year relapse-free survival in 78 investigated patients (100% versus 69 ± 7%; P=0.0003). Subgroups defined by the level of minimal residual disease in blood at day 15 (high-risk: ≥ 10(-2), intermediate-risk: <10(-2) and ≥ 10(-4), standard-risk: <10(-4)) partially correlated with bone marrow-based stratification described previously, but the risk groups did not match completely. No other time point analyses were predictive of outcome in peripheral blood, except for a weak association at day 8. CONCLUSIONS: Minimal residual disease in peripheral blood at day 15 identified a large group of patients with an excellent prognosis and added prognostic information to the risk stratification based on minimal residual disease at day 33 and week 12.

Is It Useful to Monitor Thiopurine Metabolites in Pediatric Patients with Crohn's Disease on Combination Therapy? A Multicenter Prospective Observational Study.

BACKGROUND: The additional value of azathioprine concomitant treatment on infliximab pharmacokinetics in children is not well described yet. AIMS: In the present study, we aimed to describe the relationship between thiopurine metabolite levels, infliximab trough levels, anti-IFX antibody formation, and clinical and laboratory markers of disease activity in pediatric patients with Crohn's disease, and to assess non-adherence. METHODS: Data were collected prospectively during repeated visits from pediatric patients followed for Crohn's disease in two Czech pediatric inflammatory bowel disease centers between January 2016 and June 2017. Thiopurine metabolites (6-thioguanine and 6-methylmercaptopurine) were measured by high-performance liquid chromatography. Infliximab trough levels and anti-IFX antibody serum levels were measured routinely by ELISA. The risk of loss of response to infliximab therapy was also assessed. RESULTS: A significant association between infliximab serum levels and 6-thioguanine erythrocyte levels was observed when tested as categorical variables (63 patients, 321 observations). To predict infliximab levels > 5 µg/mL, we propose a 6-thioguanine cutoff of 278 pmol/8 × 108 erythrocytes (sensitivity, 0.799; specificity, 0.347). A higher loss-of-response-to-infliximab rate (tested in a subgroup of 51 patients) was observed in patients with undetectable 6-thioguanine levels than in those with detectable levels (p = 0.026). Non-adherence to azathioprine therapy was suspected in 20% of patients. CONCLUSION: Thiopurine metabolite monitoring in pediatric patients with Crohn's disease is useful when optimizing combination therapy. Pediatric patients with undetectable 6-thioguanine levels are more likely to lose response to infliximab therapy. When targeting optimal infliximab levels, the 6-thioguanine cutoff levels in children appear to be higher than in adults.

Prognosis of children with mixed phenotype acute leukemia treated on the basis of consistent immunophenotypic criteria.

BACKGROUND: Mixed phenotype acute leukemia (MPAL) represents a diagnostic and therapeutic dilemma. The European Group for the Immunological Classification of Leukemias (EGIL) scoring system unambiguously defines MPAL expressing aberrant lineage markers. Discussions surrounding it have focused on scoring details, and information is limited regarding its biological, clinical and prognostic significance. The recent World Health Organization classification is simpler and could replace the EGIL scoring system after transformation into unambiguous guidelines. DESIGN AND METHODS: Simple immunophenotypic criteria were used to classify all cases of childhood acute leukemia in order to provide therapy directed against acute lymphoblastic leukemia or acute myeloid leukemia. Prognosis, genotype and immunoglobulin/T-cell receptor gene rearrangement status were analyzed. RESULTS: The incidences of MPAL were 28/582 and 4/107 for children treated with acute lymphoblastic leukemia and acute myeloid leukemia regimens, respectively. In immunophenotypic principal component analysis, MPAL treated as T-cell acute lymphoblastic leukemia clustered between cases of non-mixed T-cell acute lymphoblastic leukemia and acute myeloid leukemia, while other MPAL cases were included in the respective non-mixed B-cell progenitor acute lymphoblastic leukemia or acute myeloid leukemia clusters. Analogously, immunoglobulin/T-cell receptor gene rearrangements followed the expected pattern in patients treated as having acute myeloid leukemia (non-rearranged, 4/4) or as having B-cell progenitor acute lymphoblastic leukemia (rearranged, 20/20), but were missing in 3/5 analyzed cases of MPAL treated as having T-cell acute lymphobastic leukemia. In patients who received acute lymphoblastic leukemia treatment, the 5-year event-free survival of the MPAL cases was worse than that of the non-mixed cases (53+/-10% and 76+/-2% at 5 years, respectively, P=0.0075), with a more pronounced difference among B lineage cases. The small numbers of MPAL cases treated as T-cell acute lymphoblastic leukemia or as acute myeloid leukemia hampered separate statistics. We compared prognosis of all subsets with the prognosis of previously published cohorts. CONCLUSIONS: Simple immunophenotypic criteria are useful for therapy decisions in MPAL. In B lineage leukemia, MPAL confers poorer prognosis. However, our data do not justify a preferential use of current acute myeloid leukemia-based therapy in MPAL.

Identification of mutations in the ribosomal protein L5 (RPL5) and ribosomal protein L11 (RPL11) genes in Czech patients with Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is a congenital red blood cell aplasia that is usually diagnosed during early infancy. Apart from defects in red blood cell maturation, the disorder is also associated with various physical anomalies in 40% of patients. Mutations in the ribosomal protein (RP) S19 are found in 25% of patients, while mutations in other proteins of the small ribosomal subunit--RPS17 and RPS24--have been found in a fraction of patients. Recently, mutations in RPL5, RPL11, and RPL35a of the large ribosomal subunit have also been reported in several DBA patients. Here, we present the identification of mutations in the RPL5 and RPL11 genes in patients from the Czech DBA Registry. Mutations in RPL5 were identified in eight patients from 6 out of 28 families (21.4%), and mutations in RPL11 in two patients from 2 out of 28 families (7.1%). Interestingly, all 10 patients with either an RPL5 or RPL11 mutation exhibited one or more physical anomalies; specifically, thumb anomalies (flat thenar) were always present, while no such anomaly was observed in seven patients with an RPS19 mutation. Moreover, 9 out of 10 patients with either an RPL5 or RPL11 mutation were born small for gestational age (SGA) compared to 3 out of 7 patients from the RPS19-mutated group. These observations may suggest that mutations, at least in RPL5, seem to generally have more profound impact on fetal development than mutations in RPS19. Since RPL5 and RPL11, together with RPL23, are also involved in the MDM2-mediated p53 pathway regulation, we also screened the RPL23 gene for mutations; however, no mutations were identified.

Most pediatric patients with essential thrombocythemia show hypersensitivity to erythropoietin in vitro, with rare JAK2 V617F-positive erythroid colonies.

Essential thrombocythemia (ET), a Philadelphia (Ph) chromosome negative chronic myeloproliferative disorder, is usually a disease of middle age and it is extremely rare in pediatric patients. In this report we studied 12 children diagnosed with ET and one child with thrombocytosis and family history of ET. We failed to detect JAK2 V617F mutation either in peripheral blood leukocytes or in separated platelets and granulocytes. Monoclonal hematopoiesis was noted in only one female patient. Erythroid progenitors of most of the patients displayed hypersensitivity to erythropoietin (Epo) in vitro; Epo-independent erythroid colonies (EECs) were detected in seven patients. Among EECs of three patients we observed rare colonies heterozygous or homozygous for the JAK2 V617F mutation. Our data suggest that childhood ET patients could bear minor JAK2 V617F-positive subclones.

Multifarious diagnostic possibilities of the S100 protein family: predominantly in pediatrics and neonatology.

BACKGROUND: Numerous articles related to S100 proteins have been recently published. This review aims to introduce this large protein family and its importance in the diagnostics of many pathological conditions in children and adults. DATA SOURCES: Based on original publications found in database systems, we summarize the current knowledge about the S100 protein group and highlight the most important proteins with focus on pediatric use. RESULTS: The S100 family is composed of Ca2+ and Zn2+ binding proteins, which are present only in vertebrates. Some of these proteins can be used as diagnostic markers in cardiology (S100A1, S100A12), oncology (S100A2, S100A5, S100A6, S100A14, S100A16, S100P, S100B), neurology (S100B), rheumatology (S100A8/A9, S100A4, S100A6, and S100A12), nephrology and infections (S100A8, S100A9, S100A8/A9, S100A12). The most useful S100 proteins in pediatrics are S100A8, S100A9, heterodimers S100A8/A9, S100B and S100A12. CONCLUSIONS: The S100 family members are promising biomarkers and provide numerous possibilities for implementation into clinical practice to optimize the differential diagnostic process.

Acute lymphoblastic leukemia in a child with Leri-Weill syndrome and complete SHOX gene deletion: A Case Report.

BACKGROUND: Leri-Weill syndrome (LWS) ranks among conditions with short stature homeobox gene (SHOX) haploinsufficiency. Data on possible association of SHOX aberrations with malignant diseases are scarce. METHODS AND RESULTS: We report a unique case of an 8-year-old girl who was successfully treated for acute lymphoblastic leukemia (pre-B ALL, intermediate risk) and was subsequently diagnosed with LWS due to characteristic clinical appearance (short disproportionate stature, Madelung deformity of the wrist) and molecular genetic examination (complete deletion of SHOX). An identical SHOX deletion was identified also in the patient's mother. Leukemic cells of the patient were retrospectively examined by array comparative genomic hybridization (aCGH), which revealed five regions of deletions at chromosome X, including the SHOX gene locus. CONCLUSION: Growth retardation in children with hemato-oncologic malignancies cannot always be attributed to cytotoxic treatment and should be carefully evaluated, especially with regards to growth hormone therapy.

Prospective study of hypothalamo-hypophyseal dysfunction in children and adolescents following traumatic brain injury.

BACKGROUND AND AIMS: Retrospective studies of TBI have found a neuroendocrine dysfunction following traumatic brain injury in 23 to 60% of adults and 15 to 21% of children. Our aims were to determine the prevalence of hypothalamo-hypophyseal dysfunction in children following brain injury, assess its relationship to the type of injury and the course of the acute post-traumatic phase. PATIENTS AND METHODS: Body development (growth, pubertal development, and skeletal maturity) were evaluated in 58 patients (21 girls) after a brain injury rated 3 to 12 on the Glasgow Coma Scale (GCS). The patients underwent standard endocrine tests - TSH, fT4, IGF-1, PRL, morning cortisol, FSH, LH, and testosterone in boys and estradiol in girls - in the early post-traumatic period (2 to 14 days; T0) and at 3, 6, and 12 months after the injury (T3, T6, and T12). Dynamic tests were carried out in patients with abnormalities in their clinical examination and/or laboratory results. An MRI was performed on all patients at T12. RESULTS: The median age at the time of injury was 11.3 (0.5 to 18.7) years. Of the 58 patients, 23 had GCS < 8, corresponding to severe brain injury. At T0, diabetes insipidus (DI) was diagnosed in 12 patients, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was found in 4 patients. Frequent hormonal changes simulated central hypothyroidism (in 45% of patients) and hypogonadotropic hypogonadism (in 25% of adolescents who were already pubertal at the time of injury > Tanner II). Examination at T3 (n = 58) confirmed a combined pituitary hormone deficiency in two boys and DI in another one. At T6 (n = 49), hormonal dysfunctions were diagnosed in two boys (precocious puberty and growth hormone deficiency). At T12 (n = 39), a new endocrine dysfunction was diagnosed in five patients (growth hormone deficiency in two, hypogonadotropic hypogonadism in two, and in one patient, already diagnosed with a growth hormone deficiency, central hypothyroidism, as well). Brain MRI revealed an empty sella in two patients with growth hormone deficiency. Patients with GCS < 8 had more symptoms of SIADH or DI in the early post-traumatic period 11/23 vs. patients with GCS of 8 to 13 (4/35), and more frequent hormonal disorder (6/23) than individuals with moderate trauma (3/35), P = 0.0135. The incidence of endocrine dysfunction at T0 significantly correlated with the severity of injury (P = 0.05), but it was not an indicator for the development of a late hormonal disorder. CONCLUSION: Within a year after injury, a hormonal disorder was found in 17.6% of the patients. Neuroendocrine dysfunction as a late consequence of craniocerebral trauma in children and adolescents was less frequent than in adults. Risk factors for its development are the gravity of the injury, brain scan pathology, and possibly the development of DI, SIADH, or CSWS in the acute post-traumatic phase.

Increased prevalence of bicuspid aortic valve in Turner syndrome links with karyotype: the crucial importance of detailed cardiovascular screening.

BACKGROUND: Bicuspid aortic valve (BAV) represents one of the strongest risk factors for aortic dissection in Turner syndrome (TS). An exact relation between the occurrence of BAV and a particular karyotype has not been established yet. The aim of this study was to determine the association between karyotype and prevalence of BAV. METHODS: Sixty-seven TS patients aged between 6.6 and 32.5 years underwent cardiac magnetic resonance imaging (MRI) study. They were divided into four cytogenetic subgroups-45,X karyotype (n=27); 45,X/46,XX mosaicism (n=17); structural abnormalities of the X chromosome (n=10); and 45,X/structural abnormality of the X chromosome mosaicism (n=13). Prevalence of BAV and odds ratio (OR) compared with the general population in the whole study group, and statistical comparison of prevalences of BAV among the individual subgroups were determined. RESULTS: Prevalence of BAV in the whole study group was established as 28.4% [OR 208.3 (95% CI - 103.8-418.0); p-value<0.0001]. Individuals with 45,X karyotype had the highest prevalence of BAV - 40.7%, p-value<0.0001. Presence of any 45,X cell line in karyotype significantly predisposed to BAV (p-value=0.05). CONCLUSIONS: The 45,X karyotype is associated with the highest prevalence of BAV. Also, the presence of the 45,X cell line in any mosaic karyotype increases the probability of BAV.