Adequate versus deep response to ursodeoxycholic acid in primary biliary cholangitis: To what extent and under what conditions is normal alkaline phosphatase level associated with complication-free survival gain?

BACKGROUND AND AIMS: Normal alkaline phosphatase (ALP) levels in ursodeoxycholic acid (UDCA)-treated patients with primary biliary cholangitis (PBC) are associated with better long-term outcome. However, second-line therapies are currently recommended only when ALP levels remain above 1.5 times the upper limit of normal (×ULN) after 12-month UDCA. We assessed whether, in patients considered good responders to UDCA, normal ALP levels were associated with significant survival gains. APPROACH AND RESULTS: We performed a retrospective cohort study of 1047 patients with PBC who attained an adequate response to UDCA according to Paris-2 criteria. Time to liver-related complications, liver transplantation, or death was assessed using adjusted restricted mean survival time (RMST) analysis. The overall incidence rate of events was 17.0 (95% CI: 13.7-21.1) per 1000 out of 4763.2 patient-years. On the whole population, normal serum ALP values (but not normal gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST); or total bilirubin < 0.6 ×ULN) were associated with a significant absolute complication-free survival gain at 10 years (mean 7.6 months, 95% CI: 2.7 - 12.6 mo.; p = 0.003). In subgroup analysis, this association was significant in patients with a liver stiffness measurement ≥ 10 kPa and/or age ≤ 62 years, with a 10-year absolute complication-free survival gain of 52.8 months (95% CI: 45.7-59.9, p < 0.001) when these 2 conditions were met. CONCLUSIONS: PBC patients with an adequate response to UDCA and persistent ALP elevation between 1.1 and 1.5 ×ULN, particularly those with advanced fibrosis and/or who are sufficiently young, remain at risk of poor outcome. Further therapeutic efforts should be considered for these patients.

Dynamics of Liver Stiffness Measurement and Clinical Course of Primary Biliary Cholangitis.

BACKGROUND & AIMS: In primary biliary cholangitis (PBC), static liver stiffness measurement (LSM) has proven prognostic value. However, the added prognostic value of LSM time course in this disease remains uncertain. METHODS: We conducted an international retrospective cohort study among patients with PBC treated with ursodeoxycholic acid and followed by vibration-controlled transient elastography between 2003 and 2022. Using joint modeling, the association of LSM trajectory and the incidence of serious clinical events (SCE), defined as cirrhosis complications, liver transplantation, or death, was quantified using the hazard ratio and its confidence interval. RESULTS: A total of 6362 LSMs were performed in 3078 patients (2007 on ursodeoxycholic acid alone; 13% with cirrhosis), in whom 316 SCE occurred over 14,445 person-years (median follow-up, 4.2 years; incidence rate, 21.9 per 1000 person-years). LSM progressed in 59% of patients (mean, 0.39 kPa/year). After adjusting for prognostic factors at baseline, including LSM, any relative change in LSM was associated with a significant variation in SCE risk (P < .001). For example, the adjusted hazard ratios (95% confidence interval) associated with a 20% annual variation in LSM were 2.13 (1.89-2.45) for the increase and 0.40 (0.33-0.46) for the decrease. The association between LSM trajectory and SCE risk persisted regardless of treatment response or duration, when patients with cirrhosis were excluded, and when only death or liver transplantation was considered. CONCLUSIONS: Tracking longitudinal changes in LSM using vibration-controlled transient elastography provides valuable insights into PBC prognosis, offering a robust predictive measure for the risk of SCE. LSM could be used as a clinically relevant surrogate end point in PBC clinical trials.

Liver stiffness measurement by vibration-controlled transient elastography improves outcome prediction in primary biliary cholangitis.

BACKGROUND & AIMS: Liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) has been shown to predict outcomes of patients with primary biliary cholangitis (PBC) in small-size studies. We aimed to validate the prognostic value of LSM in a large cohort study. METHODS: We performed an international, multicentre, retrospective follow-up study of 3,985 patients with PBC seen at 23 centres in 12 countries. Eligibility criteria included at least 1 reliable LSM by VCTE and a follow-up ≥ 1 year. Independent derivation (n = 2,740) and validation (n = 568) cohorts were built. The primary endpoint was time to poor clinical outcomes defined as liver-related complications, liver transplantation, or death. Hazard ratios (HRs) with CIs were determined using a time-dependent multivariable Cox regression analysis. RESULTS: LSM was independently associated with poor clinical outcomes in the derivation (5,324 LSMs, mean follow-up 5.0 ± 3.1 years) and validation (1,470 LSMs, mean follow-up 5.0 ± 2.8 years) cohorts: adjusted HRs (95% CI) per additional kPa were 1.040 (1.026-1.054) and 1.042 (1.029-1.056), respectively (p <0.0001 for both). Adjusted C-statistics (95% CI) at baseline were 0.83 (0.79-0.87) and 0.92 (0.89-0.95), respectively. Between 5 and 30 kPa, the log-HR increased as a monotonic function of LSM. The predictive value of LSM was stable in time. LSM improved the prognostic ability of biochemical response criteria, fibrosis scores, and prognostic scores. The 8 kPa and 15 kPa cut-offs optimally separated low-, medium-, and high-risk groups. Forty percent of patients were at medium to high risk according to LSM. CONCLUSIONS: LSM by VCTE is a major, independent, validated predictor of PBC outcome. Its value as a surrogate endpoint for clinical benefit in PBC should be considered. LAY SUMMARY: Primary biliary cholangitis (PBC) is a chronic autoimmune disease, wherein the body's immune system mistakenly attacks the bile ducts. PBC progresses gradually, so surrogate markers (markers that predict clinically relevant outcomes like the need for a transplant or death long before the event occurs) are often needed to expedite the drug development and approval process. Herein, we show that liver stiffness measurement is a strong predictor of clinical outcomes and could be a useful surrogate endpoint in PBC trials.

Young adult patients with type 1 diabetes have a higher risk of mortality than those of similar age with type 2 diabetes: A nationwide analysis in Hungary.

BACKGROUND: There are few papers comparing complications of type 1 diabetes with those of a similarly young age with type 2 diabetes. The aim of our nationwide study was to compare the risks of mortality and morbidities between the two types of diabetes (age ≤ 40). METHODS: We identified all young adult patients with type 1 diabetes who were recorded in the database of the Hungarian National Health Insurance Fund between 2001 and 2014 (n = 11 863) and compared them with a population of similar age with young adult type 2 diabetes (n = 47 931). The incidence of all-cause mortality, myocardial infarction, stroke, any type of cancer, diabetic ketoacidosis, and hypoglycemia was followed from the onset of diabetes to the date of death or end of study period. RESULTS: The risks of all-cause mortality were significantly higher in patients with type 1 compared with patients with type 2 diabetes (hazard ratio, 95%CI; 2.17, 1.95-2.41; P < .0001). The risks of myocardial infarction (0.90, 0.71-1.13; P = 0.36) and stroke (1.06, 0.87-1.29; P = .582) were not significantly different in type 1 compared with type 2. In contrast, the risk of cancer (1.35, 1.15-1.59; P = .0003), dialysis (2.20, 1.76-2.75; P < .0001), hypoglycemia (7.70, 6.45-9.18; P < .0001), and ketoacidosis (22.12, 19.60-25.00; P < .0001) was higher among patients with type 1 compared with those with type 2 diabetes. CONCLUSIONS: A comparatively higher incidence of diabetic ketoacidosis and hypoglycemia and higher risk of cancer and dialysis in patients with type 1 diabetes than in those with type 2 may play a role in the higher risk of mortality.

Health-related quality of life of adolescents with type 1 diabetes in the context of resilience.

BACKGROUND: Adolescents with type 1 diabetes (T1D) can be faced with deterioration in glycemic control (GC), reduced health-related quality of life (HRQoL), and other psychosocial problems. It is important to understand how the disease and its clinical conditions influence HRQoL and how adolescents are able to overcome the life adjustment difficulties. OBJECTIVE: To assess HRQoL of adolescents with T1D from demographic, clinical, personal, and behavioral point of view. SUBJECTS: A total of 229 adolescents with T1D (51.2% males) with a mean age of 15.35 (2.29) years old were recruited from three diabetes centers. The mean diabetes duration was 7.48 (3.87), the mean hemoglobin A1C (HbA1c) level was 10.3 (1.76) mmol/L. METHODS: A multicenter quantitative correlational design study was applied to investigate the influence of sex, age, diabetes duration, GC expressed by HbA1c, intensive insulin regimen, physical activity (PA), resilience (RS), and socioeconomic background on HRQoL. RESULTS: Presence of the diabetes symptoms and worry about the disease has negative impact on the patients' HRQoL. Stepwise multiple regression analyses indicated that insulin pump therapy, male sex, and higher level of RS were significantly related to an increase in HRQoL, whereas the higher level of PA, male sex, and better HRQoL was significantly related to positive change in RS. Patients treated with insulin pump therapy had significantly better HRQoL. CONCLUSIONS: Significant association can be observed between HRQoL and RS. Supposedly, higher level of PA promotes higher level of RS that in turn helps increase HRQoL in adolescents with T1D. Treatment with insulin pump therapy also promotes better HRQoL.

Rupatadine is effective in the treatment of chronic spontaneous urticaria in children aged 2-11 years.

BACKGROUND: Recommendations in current guidelines for the treatment of chronic spontaneous urticaria (CSU) in infants and children are mostly based on extrapolation of data obtained in adults. This study reports the efficacy and safety of rupatadine, a modern H1 and PAF antagonist recently authorized in Europe for children with allergic rhinitis and CSU. METHODS: A double-blind, randomized, parallel-group, multicentre, placebo-controlled compared study to desloratadine was carried out in children aged 2-11 years with CSU, with or without angio-oedema. Patients received either rupatadine (1 mg/ml), or desloratadine (0.5 mg/ml) or placebo once daily over 6 weeks. A modified 7-day cumulative Urticaria Activity Score (UAS7) was employed as the primary end-point. RESULTS: The absolute change of UAS7 at 42 days showed statistically significant differences between active treatments vs. placebo (-5.5 ± 7.5 placebo, -11.8 ± 8.7 rupatadine and -10.6 ± 9.6 desloratadine; p < 0.001) and without differences between antihistamines compounds. There was a 55.8% decrease for rupatadine followed by desloratadine (-48.4%) and placebo (-30.3%). Rupatadine but not desloratadine was statistically superior to placebo in reduction of pruritus (-57%). Active treatments also showed a statistically better improvement in children's quality of life compared to placebo. Adverse events were uncommon and non-serious in both active groups. CONCLUSION: Rupatadine is effective and well tolerated in the relief of urticaria symptoms, improving quality of life over 6 weeks in children with CSU. This is the first study using a modified UAS to assess severity and efficacy outcome in CSU in children.

[Metabolic complications of obesity during adolescence, particularly regarding elevated uric acid levels]. / Az elhízás anyagcsere-szövodményei serdülokorban, különös tekintettel az emelkedett húgysavszintek elofordulására.

INTRODUCTION: Obesity is a social problem worldwide that leads to several diseases, including metabolic syndrome, hypertension and cardiovascular diseases. It is known that hyperuricemia in adults may be associated with these disorders. AIM: The aim of the authors was to investigate the frequency of metabolic syndrome and hyperuricemia and their relationship among obese adolescents. METHOD: This was a cross-sectional study. The authors analysed the data of 162 overweight or obese adolescents (100 boys and 62 girls) who were previously investigated in a paediatric endocrinology consultation. Anthropometric and metabolic parameters were evaluated in all subjects. Healthy, age-matched, non obese girls (n = 20) and boys (n = 26) were used as controls. The age of overweight or obese boys was: 12 ± 2.1 and overweight or obese girls was 11 ± 2.5 years. In the control group the age of boys was 12.9 ± 2.5 years and the age of girls was 13.2 ± 1.6 years. Linear regression was used to evaluate associations between uric acid and clinical and laboratory findings associated with metabolic syndrome. RESULTS: Obese or overweight subjects had greater BMI SDS (boys, 3.4 ± 1.3 vs 0.05 ± 0.4 in controls, p<0.0001; girls, 3.75 ± 1.4 vs 0.72 ± 0.9 in controls, p = 0.0001), waist circumference (boys, 90.1 ± 9.2 vs 82.3 ± 6.4 cm in controls; girls, 90.2 ± 8.6 vs 78.1 ± 7.2 cm in controls, p<0.001), higher systolic blood pressure (boys, 125 ± 14.3 vs 118.2 ± 10.8 mmHg in controls, p = 0.02; girls, 125.8 ± 11.8 vs 119.8 ± 8.8 mmHg in controls, p<0.01), diastolic blood pressure (boys, 78.4 ± 9.1 vs 71.2 ± 8.0 mmHg in controls, p = 0.0003; girls, 76.45 ± 7.2 vs 73.2 ± 6.3 mmHg in controls, p = 0.0453). The prevalence of metabolic syndrome was 45/162 (27.8%) and the prevalence of hyperuricemia was 62/162 (38.3%). Of the 45 subjects with metabolic syndrome, 30 (66.7%) had hyperuricemia. CONCLUSIONS: It can be concluded that hyperuricemia is strongly associated with metabolic syndrome. The high concentration of uric acid predicts cardiovascular risk in adulthood. It is important for paediatricians to determine and assess uric acid levels in overweight or obese adolescents.

[Prevalence and possible causes of hypospadias]. / A hypospadiasis gyakorisága és lehetséges okai.

Hypospadias is the most common congenital malformation of the male external genitalia. After the heart and circulatory system, it is the second most common developmental disorder in males. It is due to a midline fusion defect of the male urethra, which results in a misplaced urethral meatus. Hypospadias may be distal, medial and proximal. It may occur as an isolated defect or it may develop together with other genital disorders (retention of testes in one or both sides, microphallus, bifid scrotum) or with malformation of other organs. In some cases syndromic forms may also occur. Genetic factors play a crucial role in the occurrence of early developmental defect, but endocrine and environmental factors may also be important in the aetiology of hypospadias. It may be associated with various sex and autosomal chromosomal abnormalities. Monogenic and chromosomal causes of hypospadias accounts for about in 30% of all cases, while genetic factors remain unknown in 70% of cases. The authors summarize the development of the male external genitalia, the prevalence and possible causes of hypospadias. They propose that better understanding of the pathogenesis of the disease may contribute to the prevention and decreased prevalence of the disease.

[Questions and dilemmas in the management of hypospadias]. / A hypospadiasis ellátásában felmerülo kérdések, dilemmák.

Hypospadias is the second most common congenital malformation in males. Etiology remains unknown in about 70% of the cases. Distal hypospadias is considered not only developmental abnormality of the urethra in males, but it may also constitute a mild form of sexual development disorder in 46,XY males. Most urologists and endocrinologists consider that it is necessary to perform a detailed investigation of children presenting with proximal hypospadias associated with a small phallus or poorly developed scrotum and undescended testes. Currently, there is no generally accepted recommendation for the preoperative evaluation of hypospadias and, therefore, masculinizing surgery without preoperative evaluation is performed in these children. The authors summarize the international literature data and their own experience for the assessment and management of hypospadias concerning questions and problems related to preoperative investigation, masculinizing surgery and additional surgery. A detailed algorithm is presented for preoperative evaluation of both proximal and distal hypospadias.

Novel surfactant C variant c.325-47_374del without response to hydroxychloroquine treatment.

Pathogenic variants of SP-C, which cause various lung diseases with varying ages of onset, are inherited in an autosomal dominant manner or appear de novo as new mutations. We present a case of fatal respiratory failure in a female infant. Genetic analysis confirmed an intragenic deletion encompassing exon 4 in the SFTPC gene, starting in the intron region before exon 4, extending into the exon 4 and portion, in a heterozygous state. This variant, c.325-47_374del, in the SFTPC gene has not yet been described in the literature. Despite an experimental therapy with hydroxychloroquine, the baby girl died on Day 162.

Efficacy, drug sustainability, and safety of ustekinumab treatment in Crohn's disease patients over three years.

Long-term data on ustekinumab in real-life Crohn's disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic option. We aimed to evaluate ustekinumab's clinical efficacy, drug sustainability, and safety in a prospective, nationwide, multicenter Crohn's disease patient cohort with a three-year follow-up. Crohn's disease patients on ustekinumab treatment were consecutively enrolled from 9 Hungarian Inflammatory Bowel Disease centers between January 2019 and May 2020. Patient and disease characteristics, treatment history, clinical disease activity (Harvey Bradshaw Index (HBI)), biomarkers, and endoscopic activity (Simple Endoscopic Score for Crohn's Disease (SES-CD)) were collected for three-years' time. A total of 148 patients were included with an overall 48.9% of complex behavior of the Crohn's disease and 97.2% of previous anti-TNF exposure. The pre-induction remission rates were 12.2% (HBI), and 5.1% (SES-CD). Clinical remission rates (HBI) were 52.2%, 55.6%, and 50.9%, whereas criteria of an endoscopic remission were fulfilled in 14.3%, 27.5%, and 35.3% of the subjects at the end of the first, second, and third year, respectively. Dose intensification was high with 84.0% of the patients on an 8-weekly and 29.9% on a 4-weekly regimen at the end of year 3. Drug sustainability was 76.9% during the follow-up period with no serious adverse events observed. Ustekinumab in the long-term is an effective, sustainable, and safe therapeutic option for Crohn's disease patients with severe disease phenotype and high previous anti-TNF biological failure, requiring frequent dose intensifications.

Rupatadine oral solution in children with persistent allergic rhinitis: A randomized, double-blind, placebo-controlled study.

BACKGROUND: Allergic rhinitis (AR) is one of the most common chronic diseases in childhood. No large, multicentre clinical trials in children with persistent allergic rhinitis (PER) have previously been performed. Rupatadine, a newer second-generation antihistamine, effective and safe in adults, is a promising treatment for children with AR. The aim of the present study was to evaluate the efficacy and safety of a new rupatadine oral solution in children aged 6-11 yr with PER. METHODS: A multicenter, randomized, double-blind, placebo-controlled study was carried out worldwide. Patients between 6 and 11 yr with a diagnosis of PER according to ARIA criteria were randomized to receive either rupatadine oral solution (1 mg/ml) or placebo over 6 wk. The primary efficacy end-point was the change from baseline of the total nasal symptoms score (T4SS) after 4 wk of treatment. RESULTS: A total of 360 patients were randomized to rupatadine (n = 180) or placebo (n = 180) treatment. Rupatadine showed statistically significant differences vs. placebo for the T4SS reduction both at 4 (-2.5 ± 1.9 vs. -3.1 ± 2.1; p = 0.018) and 6 wk (-2.7 ± 1.9 vs. -3.3 ± 2.1; p = 0.048). Rupatadine also showed a statistically better improvement in the children's quality of life compared with placebo. Adverse reactions were rare and non-serious in both treatment groups. No QTc or laboratory test abnormalities were reported. CONCLUSIONS: Rupatadine oral solution (1 mg/ml) was significantly more effective than placebo in reducing nasal symptoms at 4 and 6 wk and was well tolerated overall. This is the first large clinical report on the efficacy of an H1 receptor antagonist in children with PER in both symptoms and quality of life.

Benefits of continuous subcutaneous insulin infusion on quality of life.

PURPOSE: The aim of this study was to compare the general health-related quality of life (HRQoL), the metabolic control (HbA1c), the anthropometric measurement, and the cardiorespiratory fitness (expressed by VO2max) in youths with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) to those receiving multiple daily injections (MDI). We looked for factors influencing the HRQoL and metabolic control. METHODS: A total of 239 patients treated with CSII (51 girls and 53 boys) or MDI (64 girls and 71 boys) between ages 8 and 18 years were assessed with the Pediatric Quality of Life Inventory, Generic Core Scales, and Diabetes Module. VO2max was evaluated using the 20-meter shuttle run test. RESULTS: CSII group had significantly better HRQoL according to both child self-report and parent proxy-report. Youths with CSII reported better physical, emotional, and school-related functioning, and had less diabetes-related fear and symptoms than the MDI group. There were no significant differences in body mass index z-scores, insulin doses, HbA1c, and VO2max between the groups. HRQoL was predicted by the CSII therapy (ß = -0.220; p = .000) and the VO2max (ß = 0.386; p = .000), other clinical and anthropometric parameters had no effect; the HbA1c was predicted only by VO2max (ß = -0.353; p = .000). CONCLUSIONS: Diabetic youths treated with CSII therapy have better HRQoL than those treated with MDI. There are no differences between the investigated groups in anthropometric data, glycated hemoglobin, and physical fitness. Moreover, good physical fitness has an important role in achieving better metabolic control and HRQoL, which underlines the importance of regular aerobic exercise in the treatment and care of type 1 diabetes in childhood.

[Diagnostic difficulties of polycystic ovarian syndrome in adolescent girls]. / A serdülokori polycystás ovarium szindróma diagnosztikai nehézségei.

Polycystic ovary syndrome is a heterogeneous disorder characterized by chronic ovulatory dysfunction and hyperandrogenism. It occurs in 6-8% of the female population in the reproductive age. The syndrome may be associated with various metabolic disorders which may impair the quality of life and life expectancy of patients. The diagnosis in adults is usually established by the presence of three criteria. Polycystic ovary syndrome can be also identified in adolescent girls. Although the clinical, hormonal and metabolic features are similar to those found in adult women, it may be difficult to distinguish normal adolescents from those with polycystic ovary syndrome. Irregular menstruation, anovulatory cycles, and acne are not uncommon in adolescents, and polycystic ovary syndrome may mimic physiological anovulation in adolescents. There is a high probability of polycystic ovary syndrome if anovulatory cycles persist for more than 2 years. The diagnosis of polycystic ovary syndrome in adolescents may require a unique set of criteria, however, there are no generally accepted recommendations for the diagnostic work-up. The authors propose that hyperandrogenemia is often the most reliable finding in this age group, and it may be prudent to define adolescent polycystic ovary syndrome according to the Rotterdam consensus criteria. Obesity in adolescent girls may increase the severity of symptoms of polycystic ovary syndrome and this underlines the importance of early diagnosis and treatment.

[Obesity, hormonal and metabolic abnormalities in adolescent girls with polycystic ovary syndrome]. / Elhízás, hormonális és anyagcserezavarok serdülokori polycystás ovarium szindrómában.

INTRODUCTION: Polycystic ovary syndrome is associated with metabolic abnormalities, such as dyslipidemia, obesity, glucose intolerance, which are also components of the metabolic syndrome. Central obesity and insulin resistance appear to play an important role in the pathogenesis of polycystic ovary syndrome, perhaps via subsequent steroidogenic dysregulation. AIM: The aim of the authors was to assess metabolic and hormonal abnormalities in adolescent girls with polycystic ovary syndrome. METHOD: The study included 52 adolescents diagnosed with polycystic ovary syndrome based on the Rotterdam criteria. Anthropometric, hormonal and metabolic parameters were evaluated among all subjects. 20 healthy, age-matched, non-obese, regularly menstruating girls were used as controls. Of the 52 patients, 15 patients were born with low-birth-weight and 37 patients were born with normal birth weight. Oral glucose tolerance test was performed in all patients and controls. The age of patients was 16.8±3.1 years, and the age of controls was 16.95±2.1 years. RESULTS: Among patients with polycystic ovary syndrome the prevalence of overweight and obesity was 35% (n = 18), while impaired fasting glucose occurred in one patient, impaired glucose tolerance in 8 patients, insulin resistance in 25 patients and metabolic syndrome in 12 patients. Serum triglyceride levels in patients and controls were 1.4±0.8 and 0.9±0.3 mmol/l, respectively (p<0.05), while fasting blood glucose, total cholesterol, HDL and LDL cholesterol were not different in the two groups. Metabolic abnormalities and obesity were more severe and more frequent in patients with low-birth-weight compared to those born with normal weight. There was a negative correlation between birth weight and body mass index SDS values and a positive correlation between fasting insulin levels and body mass index SDS (r = 0.37) in patients born with low-birth-weight. CONCLUSIONS: Abnormal glucose metabolism is frequently present in adolescents with polycystic ovary syndrome. It is possible that early diagnosis of polycystic ovary syndrome in adolescence may prevent some of the long-term complications associated with this syndrome.

[Peripubertal ovarian cyst torsion as an early complication of undiagnosed polycystic ovarian syndrome]. / Peripubertális petefészekciszta-torzió mint a fel nem ismert polycystás ovarium szindróma korai szövodménye.

The aim of the authors is to present two cases which raise the possibility of an association between polycystic ovarian syndrome/hyperandrogenism and ovarian cyst torsion in peripubertal girls. Androgen excess may cause more frequently ovarian cyst formation in premenarcheal or young adolescents with undiagnosed polycystic ovarian syndrome than in adults. The authors recommend that polycystic ovarian syndrome as well as late onset congenital adrenal hyperplasia should be considered in peripubertal adolescents with ovarian cyst torsion. In case polycystic ovarian syndrome is confirmed, adequate management according to age and pubertal development of the patients should be commenced.

[Role of genetic and environmental factors in the development of polycystic ovary syndrome]. / Genetikai és környezeti tényezok hatása a polycystás ovarium szindróma kialakulására.

Polycystic ovary syndrome is the most common heterogeneous endocrine abnormality in women in the reproductive age. The syndrome remains an enigmatic disorder because the aetiology is still unclear. Familial aggreagation is relatively common among patients with polycystic ovary syndrome suggesting a significant genetic component, although the way of inheritance has not been established firmly. The authors review the relevant medical literature and suggest that genetic and environmental factors play a role in the development of polycystic ovary syndrome. To date, no gene has been identified that causes or contributes substantially to the development of a polycystic ovary syndrome phenotype. Polycystic ovarian syndrome is considered to be an oligogenic disorder in which the interaction of a number of genetic and environmental factors determines the heterogeneous clinical and biochemical phenotype. To summarize current evidence the authors conclude, that when we are able to identify and then modify environmental determinants, then we will be able to safeguard better the health of those patients who are predisposed to disease development due to genotype or previous environmental effects.

[Cognitive functions in type 1 and type 2 diabetes. Meta-analysis]. / Kognitív funkciók az 1-es és 2-es típusú cukorbetegségben. Metaanalízis.

INTRODUCTION: Diabetes has been repeatedly associated with a wide variety of cognitive impairments. AIM: To clarify the differences in cognitive dysfunctions between the two types of diabetes. METHOD: Metaanalysis was performed using databases of Medline, PubMed and ScienceDirect (3 studies with type 1 and 6 with type 2 diabetes). RESULTS: Adults with type 1 diabetes showed lower performance than control subjects in all fields. The effect size had the highest value in psychomotor activity (D = -0.69). The effect size was small for delayed verbal memory (D = -0.48), attention (D = -0.47), language (D = -0.44), visual processing (D = -0.35), immediate verbal memory (D = -0.30), working memory (D = -0.27) and executive functions (D = -0.26). Adults with type 2 diabetes showed lower performance than control subjects in all cognitive domains, except for working memory (D = +0.03). The effect size had the highest value in immediate verbal memory (D = -1.12), psychomotor activity (D = -0.82) and delayed verbal memory (D = -0.81). The effect size was moderate for general intellectual abilities (D = -0.68) and small for general memory (D = -0.37), attention (D = -0.35), language (D = -0.35), visual processing (D = -0.33) and executive functions (D = -0.33). CONCLUSION: Both types of diabetes are associated with reduced performance in numerous cognitive domains.

Reduced physical fitness in children and adolescents with type 1 diabetes.

AIMS: To evaluate motor performance and cardiorespiratory function in youths with type 1 diabetes in comparison with age-matched control groups and to analyze the influence of physical activity level, anthropometric and physical fitness parameters on long-term metabolic control. METHODS: 106 youths with diabetes and 130 healthy youths aged 8-18 were assessed by the Eurofit test regarding motor performances, cardiorespiratory fitness (VO2max), skinfold thickness, and body mass index. Physical activity level was assessed through the use of questionnaires. Predictors of physical fitness and metabolic control were determined with regression analysis. RESULTS: There were no differences either in body composition or in physical activity level, but younger girls with diabetes had impaired results in speed of upper limb movement, abdominal muscle strength, upper body strength, running speed, and VO2max ; older girls with diabetes had poor results in speed of upper limb movement, abdominal muscle strength, upper body strength and VO2max . Younger boys with diabetes had impaired results in speed of upper limb movement, flexibility, static strength of hand, and abdominal muscle strength; and older boys with diabetes had poor results in speed of upper limb movement, flexibility, abdominal muscle strength, upper body strength, and VO2max compared with control groups. Older age, female gender, lower physical activity level, and higher HbA1c were significant independent predictors of poorer VO2max. Better VO2max proved to be the single predictor of favorable HbA1c . CONCLUSIONS: Youths with diabetes have reduced fitness parameters. Efforts should be carried out to improve physical fitness as part of treatment and care of children and adolescents with type 1 diabetes.

[New perspective in the treatment of chronic myeloid leukemia? gene silencing therapy]. / Új perspektíva a krónikus mieloid leukémia kezelésében? géncsendesítéses terápia.

Chronic myeloid leukemia is an incurable white blood cell disease with slow progression which affects myeloid stem cells. In the course of chromosome 22 shortening a fusion oncogene arises whose product, a Bcr-Abl oncoprotein, is a continuously expressed tyrosine kinase protein. Beside the opportunity of chemotherapy, stem cell therapy and interferon-a therapy, the application of tyrosine kinase inhibitors also became widespread in the treatment of the disease. Patients bearing the T315I point mutation, however, show resistance against all tyrosine kinase inhibitors, which can be managed by dose escalation or the combination of therapies. The discovery of RNA interference or gene silencing put the therapeutic opportunity of CML in new light. The in vitro application of anti-bcr-abl siRNA showed promising results in the causal treatment of the disease, feasible for identification of new genes associated to the disease, but we do not have sufficient evidence for the safety and efficacy of this method in human therapy.