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 PBC patients treated with ursodeoxycholic acid (UDCA) and followed by vibration-controlled transient elastography (VCTE) 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 (LT) or death, was quantified using the hazard ratio (HR) and its confidence interval (CI). RESULTS: A total of 6,362 LSMs were performed in 3,078 patients (2,007 on UDCA 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 1,000 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<0.001). For example, the adjusted HRs (95% CI) 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 LT was considered. CONCLUSIONS: Tracking longitudinal changes in LSM using VCTE 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 endpoint in PBC clinical trials.

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.

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.

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.

Continuous glucose monitoring (CGM) satisfaction and its effect on mental health and glycemic control in adults with type 1 diabetes.

Background and aim: A continuous glucose monitoring (CGM) helps the user stay continuously informed about blood glucose levels and reach the right target range. This study aimed to compare glycemic control and mental health of adults with type 1 diabetes with or without CGM and to examine their experiences using it. Methods: Patients were included in the survey, whether or not they had used a CGM. Standardized questionnaires were used to assess mental health, problems with disease management, hypoglycemia attitudes and behavior, as well as glucose monitoring satisfaction. Results: 277 people participated in the study. CGM users (61.3%) had a more favorable glycemic control than those who were not. No differences were observed between the 2 groups in mental health and in response to hypoglycemic events; however, users reported more disease-related problems. CGM users reported they felt more open and free about diabetes, however, the pain and skin irritation caused by the device was disturbing and it was difficult to cope emotionally with the constant thought and worrying about diabetes. Conclusions: CGM did not show clear satisfaction among users, however, less fear of hypoglycemia, fewer depression symptomology and improved glycemic control indicate better clinical status, which is one of the most important goals of disease management.

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.

Health-related quality of life of preschool-aged children with type 1 diabetes in the context of family and maternal functioning.

In this study, generic health-related quality of life (HRQoL) of young children with type 1 diabetes (T1D) was compared to healthy peers taken in consideration of family functioning and psychological well-being of mothers. A total of 113 mothers provided data (28 mothers had a preschool-aged child with T1D). There were no significant differences in background parameters of two investigated groups. No significant differences between children with and without T1D were detected either in HRQoL or in family functioning. Moreover, mothers of children with diabetes reported lower levels of resilience and more depressive symptoms than mothers of healthy peers. In the regression analysis, mothers' depressive symptoms and the family functioning significantly affected children's HRQoL regardless of the presence of diabetes. These results suggest that parents of children with T1D handle the burden of diabetes well and integrate into the daily activities of the families. Mothers experience distress, presumably because diabetes management is burdensome; however, the family can function well and the young children can live in a similar way to their healthy peers.

Clinical efficacy, drug sustainability and serum drug levels in Crohn's disease patients treated with ustekinumab - A prospective, multicenter cohort from Hungary.

INTRODUCTION: Although efficacy of ustekinumab (UST) has been demonstrated through randomized trials, data from real-life prospective cohorts are still limited. Our aim was to evaluate clinical efficacy, drug sustainability, dose intensification and results from therapeutic drug monitoring in UST treated patients with Crohn's disease (CD) using a prospective, nationwide, multicenter cohort. METHODS: Patients from 10 Inflammatory Bowel Disease centers were enrolled between 2019 January and 2020 May. Patient demographics, disease phenotype, treatment history, clinical disease activity (Crohn's Disease Activity Index(CDAI), Harvey Bradshaw Index(HBI)), biomarkers, and serum drug levels were obtained. Evaluations were performed at week8 (post-induction), w16-20, w32-36, and w52-56 follow-up visits. RESULTS: A total of 142 patients were included [57.4% female; complex disease behavior (B2/B3):48%, previous anti-TNF exposition:97%]. Clinical response and remission rates after induction(w8) were 78.1% and 57.7% using CDAI, and 82.5% and 51.8% based on HBI scores. The one-year clinical remission rate was 58%/57.3%(CDAI/HBI). Composite clinical and biomarker remission (CDAI<150 and C-reactive protein<10 mg/L) rates were 35.4%; 33.3%; 38.6% and 36.6% at w8/w16-20/w32-36 and w52-56. Drug sustainability was 81.9%(standard deviation(SD): 3.4) at 1 year(1y). Probability of dose intensification was high and introduced early, 42.2%(SD:4.2) at ~w32 and 51.9%(SD:4.4%) at 1y. CONCLUSION: Ustekinumab showed favorable drug sustainability and clinical efficacy in a patient population with severe disease phenotype and previous anti-tumor necrosis factor (anti-TNF) failure, however frequent dose intensification was required.

Possible explanation of the hemoglobin glycation index by the biokinetic model of glycation / A glikációs index lehetséges magyarázata a hemoglobinglikáció biokinetikus modellje alapján.

Összefoglaló. Bevezetés: A HbA1c integrált retrospektív mutatója az elmúlt idoszak vércukrának, rendszeres vizsgálata a cukorbetegek anyagcserekontrolljának megítélésében elengedhetetlen. Helyes értékelése azonban nem egyszeru, mert a HbA1c és a vércukor közötti összefüggés nem lineáris. A mérést közvetlenül megelozo hyperglykaemiás epizódok hatása a HbA1c szintjére nagyobb, mint azoké, amelyek régebben történtek. A jelenségre a glikáció biokinetikus modellje ad magyarázatot. Célkituzés: A mért és a biokinetikus modell alapján számított HbA1c közötti egyezés, illetve diszkordancia vizsgálata. Módszer: A vizsgálatokat 157, 1-es és 2-es típusú cukorbeteg 1793, laboratóriumban mért éhomi vércukor- és 511 HbA1c-adatából végeztük. A különbséget a glikációs index segítségével számítottuk, amely a mért és a számított HbA1c-érték aránya. Eredmények: Egyezést mindössze a vizsgált betegek kevesebb mint egyötödödében találtunk, 60%-ban az index értéke alacsony (<0,95) és 21%-ban magas (>1,05) volt. Az adatok részletes analízise szerint jó anyagcserekontroll esetében gyakoribb a vártnál magasabb, mért HbA1c-érték, mint a biokinetikus egyenlet által számítotté, és rosszabb kontroll (magasabb átlagos vércukor) esetében ez fordítva van. Egyezés esetén a regressziós egyenlet együtthatói gyakorlatilag azonosak a modell alapján számított értékekkel. Következtetés: Vizsgálataink felvetik azt a lehetoséget, hogy a biokinetikus modell magyarázatot adhat a vércukor és a HbA1c közötti diszkordanciára. Orv Hetil. 2021; 162(41): 1652-1657. INTRODUCTION: HbA1c is an integrated retrospective marker of previous blood glucose concentrations and its regular measurement is indispensable in the assessment of glycaemic compensation of diabetic patients. However, its proper interpretation is not simple becasuse the relationship between HbA1c and average glycemia is not a linear one. Hyperglycemic episodes occuring immediately before the measurement have greater impact on the HbA1c level as compared with those taking place earlier. OBJECTIVE: Assessment of concordance and discordance between measured and according to the biokinetic model calculated values of HbA1c. METHOD: The calculations were made from averages of 1793 fasting blood glucose and 511 HbA1c of 157, type 1 and 2 diabetic patients. The glycation index is the quotient between measured and calculated HbA1c. RESULTS: Agreement was found in less than one fifth of the 157 patients; in 60% the value of glycation was low (<0.95) and in 21% high (>1.05). Analysis of the glycation index according to the level of glycemic compensation revealed that in patients with good compensation, the measured HbA1c value was more often higher than the expected and in patients with unsatisfactory compensation the opposite was true. CONCLUSION: These results raise the possibility that the discordance between average glycemia and measured HbA1c can be explained by the biokinetic model. Orv Hetil. 2021; 162(41): 1652-1657.

Insulin resistance and its effects in children and adolescents / Inzulinrezisztencia és következményei gyermek- és serdülokorban.

Összefoglaló. Számos adat igazolja, hogy az inzulinrezisztencia gyakori jelenség gyermek- és serdülokorban, és szoros kapcsolatban áll a cardiovascularis kockázat növekedésével, ami miatt a kérdéskörre az életnek ebben a korai szakaszában is kiemelt figyelmet kell fordítani. Ma már egyre több ismerettel rendelkezünk a kockázati tényezoket illetoen, nincs azonban egységes álláspont az inzulinrezisztencia meghatározására vonatkozóan a klinikai gyakorlatban, és nem rendelkezünk megfelelo laboratóriumi markerekkel, melyek segítségével a veszélyeztetetteket széles körben eredményesen lehetne azonosítani. Mindezek alapján a laboratóriumi módszerrel történo szurés ebben az életkorban nem indokolt, azonban a társuló és következményes kórállapotok klinikai alapon történo felismerésére törekedni kell. A cardiovascularis kockázat megelozésére irányuló életmódbeli prevenció hatásos az inzulinrezisztencia csökkentésében, a gyakorlatban azonban kivitelezése és eredményessége korlátozott. A gyógyszeres intervenció jelenleg ebben az életkorban csak egyes szelektált esetekben kerülhet alkalmazásra. További klinikai kutatásokra van szükség az inzulinrezisztencia mérése, az életmódbeli és gyógyszeres intervenciós lehetoségek területén annak érdekében, hogy sikeres stratégiák legyenek kialakíthatók a cardiovascularis halálozás megelozése, csökkentése érdekében. Orv Hetil. 2021; 162(11): 403-412. Summary. Numerous data confirm that insulin resistance is a common phenomenon in children, and closely links to an increase in cardiovascular risk, therefore it is urgent to pay attention to this from early childhood. Today, we have more and more knowledge about risk factors, but there is no common position on the definition of insulin resistance in clinical practice and we do not have adequate laboratory markers to identify those at risk effectively. Based on all these factors, laboratory screening is not justified at this age, however, efforts should be made to recognize associated and consequent conditions on a clinical basis. Lifestyle prevention to prevent cardiovascular risk is effective in reducing insulin resistance, but in practice its implementation and effectiveness are limited. At present, pharmacological intervention can only be used in certain selected cases with this age group. Further clinical research is needed to measure insulin resistance, lifestyle and drug intervention options in order to develop successful strategies to prevent and reduce cardiovascular death. Orv Hetil. 2021; 162(11): 403-412.

Changes in the incidence and prevalence of type 1 and type 2 diabetes among 2 million children and adolescents in Hungary between 2001 and 2016 - a nationwide population-based study.

INTRODUCTION: The aim of the present study was to assess changes in the incidence and prevalence of type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in children and adolescents in Hungary during the period 2001 to 2016 in order to provide nationwide population-based epidemiology data on diabetes in youths aged 0-18 years. MATERIAL AND METHODS: This was a retrospective cohort study of Hungarian children and adolescents aged 18 years or younger. Pharmacologically treated diabetes cases were obtained through a population-based registry of the Hungarian National Health Insurance Fund. Time series analysis was used to evaluate the changing patterns of the incidence and prevalence for type 1 and type 2 diabetes covering a 16-year period. RESULTS: During the study period, 6,138 and 1,997 new T1DM and T2DM cases were observed, respectively. Newly diagnosed T2DM cases accounted for 24.5% of all incident diabetes cases. Incidence of T1DM increased from 16/100,000 to 23/100,000 (R 2 = 0.7681; p < 0.0001). The male-to-female ratio among newly diagnosed T1DM patients did not change over the study period. Prevalence of T1DM rose from 114/100,000 to 209/100,000 (R 2 = 0.9909; p < 0.0001). The prevalent T1DM cases showed significant male predominance in every year (p < 0.05). Incidence of T2DM decreased from 8/100,000 to 5/100,000 (R 2 = 0.4977; p < 0.0014). The overall prevalence of T2DM did not change significantly. Prevalent T2DM cases showed significant female predominance in every year (p < 0.0001). A significant decrease in male-to female ratio was observed among newly diagnosed T2DM cases over the study period (p < 0.0001). CONCLUSIONS: According to these population-based Hungarian data of children and adolescents with diabetes, T1DM is still the most common form and its frequency continues to rise, affecting more males than females. A high proportion of patients have T2DM, affecting more females than males, but the occurrence of medically treated cases is not increasing. The decrease in male-to-female ratio in newly diagnosed T2DM cases needs further investigations.

[Community-acquired bacterial infections among type 2 diabetic and non-diabetic patients hospitalized on a general medical ward: a clinical comparison]. / 2-es típusú diabetesesek és nem cukorbetegek területen szerzett, belgyógyászati osztályos felvételt igénylo bakteriális infekcióinak klinikai összehasonlítása.

Introduction: Previous data showed bacterial infections among diabetic patients to be more serious and frequent, with higher mortality rates in comparison with non-diabetics. Recent investigations, however, are contradictory. Aim: The goal of our prospective, observational study was to compare patients hospitalized on a general medical ward due to community-acquired bacterial infections with type 2 diabetes mellitus (T2DM) to those of non-diabetics (K) by 1) infection localization, 2) spectrum of pathogens, 3) three-month mortality rates. Method: Patients were consecutively involved (T2DM: n = 205, K: n = 202). We characterized the infections, clinical parameters, mortalities of the two groups, and matched them to international data. Results: No difference regarding clinical details of the groups were found except for glycemic parameters and BMI. In the T2DM group the skin- and soft tissue- (37.1%), in the K patients respiratory infections (37.1%) were the most common, followed by urinary ones (31.2% and 31.7%, respectively). Skin- and soft tissue infection incidence among T2DM subjects were higher compared to international results (37.1% vs. 16%). Co-presence of Gram positive and Gram negative bacteria in the skin- and soft tissue infections (23/76 vs. 5/46, p = 0.0149), and polymicrobial origin in the urinary tract infections (34.0% vs. 15.1%, p = 0.0335) were found to be more frequent in T2DM than in K. No difference regarding mortality rates were detected. In T2DM the skin- and soft tissue while in the K group the respiratory infections had the most death counts. Conclusions: We found higher rates of skin- and soft tissue infections among T2DM patients hospitalized on a general medical ward compared to international data. In total we did not find difference regarding three-month mortality between the groups. Our results highlight the importance of primary prevention and shows its inadequacy concerning skin and soft tissue infections among type 2 diabetics in Hungary. Orv Hetil. 2019; 160(41): 1623-1632.

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.

Decreased Ficolin-3-mediated Complement Lectin Pathway Activation and Alternative Pathway Amplification During Bacterial Infections in Patients With Type 2 Diabetes Mellitus.

Bacterial infections are frequent and severe in patients with diabetes mellitus. Whether diabetes per se induces functional alterations in the complement system hampering activation during infection is unknown. We investigated key elements of the complement system during bacterial infections in patients with type 2 diabetes mellitus (T2DM) and compared them to non-diabetic (ND) individuals. Using a prospective design, we included 197 T2DM, and 196 ND subjects, all with clinical diagnosis of acute community-acquired bacterial infections. Functional activities of the ficolin-3-mediated lectin (F3-LP), mannose binding lectin-mediated lectin- (MBL-LP), classical (CP), and alternative pathways (AP), as well as concentrations of complement activation products C4d and sC5b-9 were determined. Functional in vitro activities of F3-LP and AP were significantly higher in T2DM than in ND subjects, (median 64% vs. 45%, p = 0.0354 and 75 vs. 28%, p = 0.0013, respectively), indicating a decreased in vivo activation and lack of consumption of F3-LP and AP in T2DM patients, whereas no difference in functional capacities of CP and MBL-LP were observed between T2DM and ND subjects. Diminished F3-LP and AP activation was most pronounced in diabetic patients with urinary tract infections with positive microbiological culture results for Escherichia coli bacteria. In the T2DM group 3-months mortality significantly associated with diminished F3-LP and AP, but not with CP activation. Concentrations of C4d and sC5b-9 were significantly lower in the T2DM than in ND patients. In conclusion, we found impaired F3-LP activation and lack of AP amplification during bacterial infections in patients with type 2 diabetes, compared to non-diabetic subjects, suggesting a diminished complement mediated protection to bacterial infections in T2DM.

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.

Large increase in the prevalence of self-reported diabetes based on a nationally representative survey in Hungary.

AIMS: To estimate and compare the prevalence of self-reported diabetes based on nationally representative surveys of the Hungarian adult population in 2002 (published data - Hungarostudy) and a survey in 2012. METHODS: A cross-sectional computer-assisted telephone interview survey on a stratified representative sample of community-dwelling adults (n=1000) in 2012. To describe self-reported diabetes prevalence and its temporal changes generalized linear models were used and results were compared to figures from Hungarostudy. RESULTS: Age standardized prevalence of self-reported type 2 diabetes was 11.7% (95%CI 10.0-13.8%) without gender or rural-urban differences in 2012. People with self-reported diabetes were older than controls (mean [SE]: 63.9 [0.9] vs. 45.9 [0.3] years, p<0.0001). The prevalence of diabetes sharply increased after 40 years of age and peaked at age 70 (27.7% [2.5], page*age<0.0001). The prevalence of self-reported diabetes increased by 89% (OR 1.89, 95%CI 1.53-2.32) from 6.2 to 11.7% between the two surveys with the most pronounced increase in the age group 55-64 years (from 11.6 to 24.4%). CONCLUSIONS: We reported an alarming increase in the prevalence of self-reported type 2 diabetes in the last decade that mostly affects working age people. If this trend continues, a major public health crisis in Hungary can be envisaged.

Generic and disease-specific quality of life in adolescents with type 1 diabetes: comparison to age-matched healthy peers.

BACKGROUND: This study aimed to evaluate the health-related quality of life (HRQoL) of adolescents with type 1 diabetes (T1DM) on the basis of the pediatric quality of life inventory™ (PedsQL™) generic and diabetes-specific modules, and to compare it to that of healthy peers. METHODS: This retrospective case-control study involved 650 participants between ages of 13 and 19 years including 296 adolescents with T1DM from four diabetes centers and 354 healthy peers matched for age and gender from three different cities of the country. Participants completed the validated PedsQL™ for assessing the HRQoL. The analysis included an independent t-test to compare the means of the total and subscales of the PedsQL™ between boys and girls as well as between a healthy group and a group with T1DM. Gender differences in exercise, insulin therapy modalities were evaluated with the Pearson χ2-test. RESULTS: Adolescents with T1DM have similar HRQoL in all domains when compared to their healthy counterparts. Females report worse HRQoL regardless of the presence of the disease. Insulin pump therapy facilitates better glycemic control and HRQoL. Regular exercise positively correlates with the generic HRQoL in both groups; however, it has no relationship with glycemic control. CONCLUSIONS: Optimal metabolic control and improved HRQoL are the eventual goals of diabetes management. Despite the difficulties, adolescents with diabetes can manage their disease well and live normal lives, similar to their healthy peers. Although diabetes-related problems exist, it seems that regular exercise and staying physically active, as well as promoting insulin pump therapy where it is applicable are related to favorable HRQoL.

A cross-cultural study on perceived health-related quality of life in children and adolescents with type 1 diabetes mellitus.

OBJECTIVE: This study investigated whether culture can affect self- and proxy-reports of perceived diabetes-specific health-related quality of life of children and adolescents with type 1 diabetes when taking into account glycemic control, gender and age. METHODS: A total of 416 patients aged between 8 and 18 years--84 (Greece), 135 (Hungary) and 197 (Kuwait)--and their parents completed the Pediatric Quality of Life Inventory 3.0. Diabetes Module. RESULTS: Gender and age did not have any effect on perceived diabetes-specific health-related quality of life. Significant differences were detected among countries in self- and proxy-reports of diabetes-specific health-related quality of life when controlling for glycemic control. More specifically, Greek patients with type 1 diabetes and their parents reported significantly worse disease-specific health-related quality of life than their peers from Kuwait and Hungary. Moreover, culture affected the level of agreement between self- and proxy-reports with parents from Kuwait underestimating their children's diabetes-specific health-related quality of life. CONCLUSION: The impact of culture on self- and proxy-reports of diabetes-specific health-related quality of life warrants further investigation, since it might suggest the need for differential psychosocial treatment.

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.