Search

AIMS To assess the differences in key parameters of type 1 diabetes (T1D) control associated with treatment and monitoring modalities including newly introduced hybrid closed-loop (HCL) algorithm in children and adolescents with T1D (CwD) using the data from the population-wide pediatric diabetes registry ČENDA. MATERIALS AND METHODS CwD younger than 19 years with T1D duration > 1 year were included and divided according to the treatment modality and type of CGM used: multiple daily injection (MDI), insulin pump without (CSII) and with HCL function, intermittently scanned continuous glucose monitoring (isCGM), real-time CGM (rtCGM), and intermittent or no CGM (noCGM). HbA1c, times in glycemic ranges, and glucose risk index (GRI) were compared between the groups. RESULTS Data of a total of 3251 children (mean age 13.4± years) were analyzed. 2187 (67.3%) were treated with MDI, 1064 (32.7%) with insulin pump, 585/1064 (55%) with HCL. The HCL users achieved the highest median TIR 75.4% (IQR 6.3), and GRI 29.1 (7.8), both p

Introduction: Currently used molecular diagnostic tests for colorectal cancer (CRC) are underperforming and more sensitive, non-invasive biomarkers are needed. Long non-coding RNAs (lncRNA) and microRNA (miRNA) have shown potential as diagnostic biomarkers. Unfortunately, the identification of non-coding RNA circulating biomarkers in blood serum is significantly burdened by abundant RNA specimens from disrupted blood cells. Recently, small extracellular vesicles (sEVs) emerged as potential reservoirs of clinically relevant biomarkers, including lncRNAs and miRNAs. In theory, sEVs protect RNAs from degradation and might serve as a source of intact RNA for further analyses. However, there is a lack of evidence supporting the superior quality of RNA extracted from sEVs over RNA from whole blood serum. This study aimed to analyze the RNA content of blood serum and the sEVs derived from the blood serum of CRC patients and healthy controls using RNA sequencing. Moreover, small RNA sequencing was used to evaluate the difference in miRNA profiles of sEVs and corresponding blood sera of CRC patients and healthy controls. Methods: Spin-column chromatography (Exiqon), precipitation-based method (Norgen), and size-exclusion chromatography (iZON) were used to extract sEVs from blood sera. The concentration of sEVs was measured by dynamic light scattering (DLS), the size was evaluated by electron microscopy (EM), and sEV-specific content was analyzed by western blot and qRT-PCR. RNA was extracted using the column-based method. Next-generation sequencing (NGS) analyses of blood serum and sEVs extracted from blood serum included samples from 10 CRC patients and 10 healthy controls for RNAseq, and 5 CRC patients and 5 healthy controls for small RNAseq. Differential expression analysis was carried out in R using DESeq2 package. Results: DLS and EM showed that size-exclusion chromatography yielded the purest population of sEVs characterized according to ISEV recommendations. Extraction of sEVs and subsequent RNA extraction and sequencing library preparation from ultra-low input samples were optimized. Over 30k different RNAs were identified in the sEVs derived from blood sera of CRC patients and healthy controls, including lncRNAs, miRNAs, and protein-coding RNAs. A detailed comparison of the transcriptome of blood sera and corresponding sEVs is a part of the poster. Conclusion: sEVs could serve as a source of RNA biomarkers; however, proper characterization and optimal methodology are necessary. This work was supported by the Ministry of Health of the Czech Republic grant No. NU20-03-00127, by The project National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) - Funded by the European Union - Next Generation EU, by the project BBMRI-CZ, nr. LM2018125, and in co-operation with CEMCOF, CEITEC MU (CIISB) supported by MEYS CR, LM2018127. Citation Format: Tana Machackova, Petra Vychytilova-Faltejskova, Marie Madrzyk, Karolina Trachtova, Marketa Pavlikova, Jan Kotoucek, Jana Halamkova, Dagmar Al Tukmachi, Jiri Sana, Petra Pokorna, Milana Sachlova, Ondrej Slaby. Utility of RNA sequencing for transcriptome analysis of small extracellular vesicles derived from blood sera of colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6709.

Correct genetic diagnosis of maturity-onset diabetes of the young (MODY) is beneficial for person's diabetes management compared to no genetic testing. Aim of the present study was a search for optimal time- and cost-saving strategies by comparing two approaches of genetic testing of participants with clinical suspicion of MODY.A total of 121 consecutive probands referred for suspicion of MODY (Group A) were screened using targeted NGS (tNGS), while the other 112 consecutive probands (Group B) underwent a single gene test based on phenotype, and in cases of negative findings, tNGS was conducted. The study was performed in two subsequent years. The genetic results, time until reporting of the final results and financial expenses were compared between the groups.MODY was confirmed in 30.6% and 40.2% probands from Groups A and B, respectively; GCK-MODY was predominant (72.2% in Group A and 77.8% in Group B). The median number of days until results reporting was 184 days (IQR 122-258) in Group A and 91 days (44-174) in Group B (p 0.00001). Mean costs per person were higher for Group A (639 ± 30 USD) than for Group B (584 ± 296 USD; p = 0.044).The two-step approach represented a better strategy for genetic investigation of MODY concerning time and costs compared to direct tNGS. Although a single-gene investigation clarified the diabetes aetiology in the majority of cases, tNGS could reveal rare causes of MODY and expose possible limitations of both standard genetic techniques and clinical evaluation.

Aims/hypothesis: The proportion of children with type 1 diabetes (T1D) who have experience with low-carbohydrate diet (LCD) is unknown. Our goal was to map the frequency of LCD among children with T1D and to describe their clinical and laboratory data. Methods: Caregivers of 1040 children with T1D from three centers were addressed with a structured questionnaire regarding the children’s carbohydrate intake and experience with LCD (daily energy intake from carbohydrates below 26% of age-recommended values). The subjects currently on LCD were compared to a group of non-LCD respondents matched to age, T1D duration, sex, type and center of treatment. Results: A total of 624/1040 (60%) of the subjects completed the survey. A total of 242/624 (39%) subjects reported experience with voluntary carbohydrate restriction with 36/624 (5.8%) subjects currently following the LCD. The LCD group had similar HbA1c (45 vs. 49.5, p = 0.11), lower average glycemia (7.0 vs. 7.9, p = 0.02), higher time in range (74 vs. 67%, p = 0.02), lower time in hyperglycemia &gt, 10 mmol/L (17 vs. 20%, p = 0.04), tendency to more time in hypoglycemia &lt, 3.9 mmol/L(8 vs. 5%, p = 0.05) and lower systolic blood pressure percentile (43 vs. 74, p = 0.03). The groups did not differ in their lipid profile nor in current body height, weight or BMI. The LCD was mostly initiated by the parents or the subjects themselves and only 39% of the families consulted their decision with the diabetologist. Conclusions/interpretation: Low carbohydrate diet is not scarce in children with T1D and is associated with modestly better disease control. At the same time, caution should be applied as it showed a tendency toward more frequent hypoglycemia.

Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD/MTPD) and medium chain acyl-CoA dehydrogenase deficiency (MCADD) were included in the expanded neonatal screening program (ENBS) in Czechia in 2009, allowing for the presymptomatic diagnosis and nutritional management of these patients. The aim of our study was to assess the nationwide impact of ENBS on clinical outcome. This retrospective study analysed acute events and chronic complications and their severity in pre-ENBS and post-ENBS cohorts. In total, 28 children (12 before, 16 after ENBS) were diagnosed with LCHADD/MTPD (incidence 0.8/100,000 before and 1.2/100,000 after ENBS). In the subgroup detected by ENBS, a significantly longer interval from birth to first acute encephalopathy was observed. In addition, improvement in neuropathy and cardiomyopathy (although statistically non-significant) was demonstrated in the post-ENBS subgroup. In the MCADD cohort, we included 69 patients (15 before, 54 after ENBS). The estimated incidence rose from 0.7/100,000 before to 4.3/100,000 after ENBS. We confirmed a significant decrease in the number of episodes of acute encephalopathy and lower proportion of intellectual disability after ENBS (p &lt, 0.0001). The genotype–phenotype correlations suggest a new association between homozygosity for the c.1528C &gt, G variant and more severe heart involvement in LCHADD patients.

ObjectivesMicroRNAs (miRNAs) are short single-stranded RNAs that play a role in the post-transcriptional regulation of gene expression. Their deregulation can be associated with various diseases, such as cancer, neurodegenerative, and immune-related diseases. The aim of our study was to compare miRNA levels in plasma that could potentially influence the progression of hyperuricemia to gout, since the mechanism of progression is still unclear.MethodsTotal RNA, including miRNA, was isolated from the plasma of 45 patients with asymptomatic hyperuricemia, 131 patients with primary gout (including 16 patients having a gout attack), and 130 normouricemic controls. The expression of 18 selected miRNAs (cel-miR-39 and cel-miR-54 as spike-in controls, hsa-miR-16-5p and hsa-miR-25-3p as endogenous controls, hsa-miR-17-5p, hsa-miR-18a-5p, hsa-miR-30a-3p, hsa-miR-30c-5p, hsa-miR-126-3p, hsa-miR-133a-3p, hsa-miR-142-3p, hsa-miR-143-3p, hsa-miR-146a-5p, hsa-miR-155-5p, hsa-miR-222-3p, hsa-miR-223-3p, hsa-miR-488-3p and hsa-miR-920) was measured using qPCR.ResultsWe found that hsa-miR-17-5p, hsa-miR-18a-5p, hsa-miR-30c-5p, hsa-miR-142-3p, and hsa-miR-223-3p were significantly upregulated (pConclusionFive miRNAs were significantly upregulated in the plasma of patients with hyperuricemia and gout (and those during a gout attack) compared to normouricemic controls. We also found a correlation between the plasma levels of several miRNA and plasma levels of MCP-1, CRP, serum creatinine, and eGFR.

Background Females with Turner syndrome (TS) are prone to develop autoimmune diseases (AIDs). The X chromosome contains several immune-related genes. Growth hormone (GH) and estrogens modulate the immune system. We aimed to clarify whether the loss of a specific X chromosome gene locus and the administration of GH and estradiol facilitate the development of AIDs in TS females. Methods Retrospective data on clinical course, AIDs, karyotype and treatment were analyzed from a cohort of 286 Czech females with TS (current age 2.8–43.3 years; median age 18.7 years). The karyotypes were sorted using two different classification systems: a mosaicism-focused and an isochromosome (isoXq)-focused approach. Karyotype subgroups with a significantly higher prevalence of AIDs were further evaluated. Data of common therapies were correlated with the prevalence of AIDs. Results The most frequent AIDs were autoimmune thyroid disease (AITD; 37.4%; n = 107) and celiac disease (CD; 8.7%; n = 25). All karyotype subgroups were prone to develop AIDs. Females with an isolated Xp deletion had a significantly higher prevalence of AITD and CD compared to all other individuals with TS (AITD: 66.0% vs. 31.5%, p Conclusions Isolated Xp deletion contributes to the development of AIDs in TS patients. The haploinsufficiency of genes located in Xpter-p11.2 may explain this observation. Common therapies used in TS do not modify the risk of AIDs.

Increased access to modern technologies is not always accompanied by a decrease in HbA1c. The aim of this study was to identify changes in the proportion of continuous glucose monitoring (CGM) users since 2017, when general reimbursement for CGM became effective in Czechia, and to test whether HbA1c is associated with the percentage of time spent on CGM.All T1D children in the Czech national ČENDA registry (3197 children) were categorized according to their time spent on CGM and associations with age, sex, center size, and HbA1c were tested with calendar year as a stratification factor.The proportion of children with any CGM use increased from 37.9% in 2017 to 50.3% in 2018 and 74.8% in 2019. Of the CGM users, 16%, 28%, and 41% of the children spent70% of their time on CGM over the 3 years of the study period, with an overrepresentation of children in the10 years age group versus the older age groups (p 0.001). The proportion of CGM users differed among centers and was positively associated with a large center size (100 patients) (p 0.001). HbA1c was negatively associated with the time spent on CGM (p 0.001).A rapid increase in CGM use was reported over the 3 years after general reimbursement. HbA1c was associated with time spent on CGM, a continuing decrease was observed in the70% category. Reimbursement for CGM likely contributes to the improvement of T1D control at the population level.

Urate transporters, which are located in the kidneys, significantly affect the level of uric acid in the body. We looked at genetic variants of genes encoding the major reabsorption proteins GLUT9 (SLC2A9) and URAT1 (SLC22A12) and their association with hyperuricemia and gout. In a cohort of 250 individuals with primary hyperuricemia and gout, we used direct sequencing to examine the SLC22A12 and SLC2A9 genes. Identified variants were evaluated in relation to clinical data, biochemical parameters, metabolic syndrome criteria, and our previous analysis of the major secretory urate transporter ABCG2. We detected seven nonsynonymous variants of SLC2A9. There were no nonsynonymous variants of SLC22A12. Eleven variants of SLC2A9 and two variants of SLC22A12 were significantly more common in our cohort than in the European population (p = 0), while variants p.V282I and c.1002+78A&gt, G had a low frequency in our cohort (p = 0). Since the association between variants and the level of uric acid was not demonstrated, the influence of variants on the development of hyperuricemia and gout should be evaluated with caution. However, consistent with the findings of other studies, our data suggest that p.V282I and c.1002+78A&gt, G (SLC2A9) reduce the risk of gout, while p.N82N (SLC22A12) increases the risk.

Aims We investigated the quality of life (QoL), treatment satisfaction and perception of genetic results in participants with Maturity-Onset Diabetes of the Young (MODY) and compared the results with those of subjects with type 1 (T1D) or type 2 (T2D) diabetes. Methods A total of 162 adults with GCK-MODY, 62 with HNF1A-MODY and 29 with HNF4A-MODY answered the questionnaire Audit of Diabetes Dependent Quality of Life, the Diabetes Treatment Satisfaction Questionnaire and non-validated instrument examining the respondent’s perception of the genetic results. Data from GCK-MODY patients were compared with 84 participants with T2D and HNF-MODY subjects were compared with 81 participants having T1D. Results Higher age (p=0.004), higher haemoglobin A1c (p=0.026) and medication (p=0.019) were associated with lower general QoL in GCK-MODY patients. In HNF-MODY patients, lower general QoL was associated with a longer time since diagnosis (p=0.005), worse haemoglobin bA1c (p=0.006) and insulin treatment (p=0.019). Similar numbers of participants with GCK- and HNF-MODY considered the genetic diagnosis of MODY to be positive, negative and without significance. The patient with GCK-MODY did not differ from those with T2D in terms of their QoL, but they were less satisfied with their treatment (p Conclusions QoL was affected in both GCK-MODY and HNF-MODY subjects. Apprehension of genetic diagnosis was not single-valued in MODY respondents.

Background Functional electric stimulation (FES) is recommended for foot drop in multiple sclerosis, although little is known about its therapeutic effect. Aim The aim of this study is to evaluate a therapeutic effect immediately and two months after program termination (persistent and delayed effect) of a new approach using FES in combination with correcting the patients' postural system. More specifically, we evaluate the effects of this approach on the patients' clinical functions and compared it with individual physiotherapy. Design Parallel randomized blind trial. Setting Two-month-long treatments, functional electric stimulation in posturally corrected position (group 1) and neuroproprioceptive facilitation and inhibition physiotherapy called motor program activating therapy (group 2). Population Forty-four subjects with multiple sclerosis. Methods Primary outcomes: gait (the 2-Minute Walk Test; Timed 25-Foot Walk test; Multiple Sclerosis Walking Scale-12) and balance (by e.g. Berg Balance Scale [BBS], the Activities-Specific Balance Confidence Scale [ABC], Timed Up-and-Go Test [TUG]). Secondary outcomes mobility, cognition, fatigue and subjects' perceptions (e.g. Multiple Sclerosis Impact Scale [MSIS], Euroqol-5 dimensions-5 levels [EQ-5D-5L]). Results Group 1 showed immediate therapeutic effect in BBS (P=0.008), ABC (P=0.04) and EQ-5D-5L (self-care, P=0.019, mobility P=0.005). The improvement in EQ-5D-5L persisted and in TUG-cognitive we documented a delayed effect (P=0.005). Group 2 showed an immediate improvement in BBS (P=0.025), MSIS (P=0.043) and several aspects of daily life (the effect on health today was significantly higher than in group 1, significant difference between groups P=0.038). Conclusions FES in the posturally corrected position has an immediate therapeutic effect on balance and patients' perceptions comparable to motor program activating therapy, and higher persistent and even delayed therapeutic effect. Clinical rehabilitation impact The study results point to the importance of correcting the patients' posture when applying FES, the possibility to treat foot drop by individual physiotherapy and the activation of the patients' auto reparative processes.

Background: The pathogenesis of adolescent idiopathic scoliosis (AIS), including the role of brain and spinal inhibitory circuits, is still poorly elucidated. The aim of this study was to identify which central inhibitory mechanisms are involved in the pathogenesis of AIS. Design: A prospective neurophysiological study, using a battery of neurophysiological tests, such as cutaneous (CuSP) and cortical (CoSP) silent periods, motor evoked potentials (MEP) and paired-pulse transcranial magnetic stimulation (ppTMS). Settings: Neurophysiological laboratory. Participants: Sixteen patients with AIS (14 females, median age 14.4) and healthy controls. Outcome measures: MEPs were obtained after transcranial magnetic stimulation (TMS) and recorded from the abductor pollicis muscle (APB). ppTMS was obtained at interval ratios (ISI) of 1, 2, 3, 6, 10, 15 and 20 ms. The cortical silent period (CoSP) was recorded from the APB. The cutaneous silent period (CuSP) was measured after painful stimuli delivered to the thumb while the subjects maintained voluntary contraction of the intrinsic hand muscles. The data were analyzed and compared with those from healthy subjects. Results: The CoSP duration was significantly prolonged in AIS patients. A significantly higher amplitude of ppTMS for ISI was found in all AIS patients, without remarkable left-right side differences. No significant difference in MEP latency or amplitude nor in the CuSP duration was obtained. Conclusion: Our observation demonstrates evidence of central nervous system involvement in adolescent idiopathic scoliosis (AIS). Lower intracortical inhibition, higher motor cortex excitability, and preserved spinal inhibitory circuits are the main findings of this study. A possible explanation of these changes could be attributed to impaired sensorimotor integration predominantly at the cortical level.

Contains fulltext : 169680.pdf (Publisher’s version ) (Open Access) Cystathionine beta-synthase (CBS) deficiency is a rare inherited disorder in the methionine catabolic pathway, in which the impaired synthesis of cystathionine leads to accumulation of homocysteine. Patients can present to many different specialists and diagnosis is often delayed. Severely affected patients usually present in childhood with ectopia lentis, learning difficulties and skeletal abnormalities. These patients generally require treatment with a low-methionine diet and/or betaine. In contrast, mildly affected patients are likely to present as adults with thromboembolism and to respond to treatment with pyridoxine. In this article, we present recommendations for the diagnosis and management of CBS deficiency, based on a systematic review of the literature. Unfortunately, the quality of the evidence is poor, as it often is for rare diseases. We strongly recommend measuring the plasma total homocysteine concentrations in any patient whose clinical features suggest the diagnosis. Our recommendations may help to standardise testing for pyridoxine responsiveness. Current evidence suggests that patients are unlikely to develop complications if the plasma total homocysteine concentration is maintained below 120 mumol/L. Nevertheless, we recommend keeping the concentration below 100 mumol/L because levels fluctuate and the complications associated with high levels are so serious.

We analyzed primary school performance of girls with Turner syndrome (TS) in two distinct countries to ascertain if the cognitive phenotype of TS causes selective learning difficulties.The cohort comprised of 44 Czech and 50 Egyptian girls with TS who attended public schools. School reports from grades 1 to 9 were obtained retrospectively from Czech participants with TS. Only recent school reports were obtained from Egyptian participants. Two controls per participant were requested - biological sisters and/or female classmates. The results were converted into a 5-point scale (1-excellent; 5-unsatisfactory).Analysis of longitudinal Czech data displayed a strong time component in both subjects and controls. Showing better points in lower grades with its gradual worsening as the education complexity increased. In contrast, there was a strong statistically significant difference between groups in Mathematics (p=0.0041, p=0.0205 after Bonferroni correction) and this difference increased over time. The points for Mathematics did not differ in grades 1+2 (0.05 difference in mean grade between the two groups), however, they differed by 0.28 in grades 6+7 and by 0.32 in grades 8+9. While slightly different in character (cross-sectional vs. longitudinal), the Egyptian cohort data confirmed our findings, showing no difference in general school performance but having similar trends in Mathematics (grades 1+2: 0.11, grades 6+7: 0.54, grades 8+9: 0.68; p=0.0058, p=0.029 after Bonferroni correction).Excluding results in Mathematics, which showed pronounced worsening in relation to age in comparison with unaffected controls, girls with TS performed similarly to their controls.

The development of the immune phenotype in patients with type 1 diabetes (T1D) during the first year following disease onset remains poorly described, and studies analysing the longitudinal development of a complex set of immunological and metabolic parameters are missing. Thus, we aim to provide such complex view in a cohort of 38 children with new onset T1D who were prospectively followed for 1 year. All subjects were tested for a set of immunological parameters (complete blood count; serum immunoglobulins; and T, B and dendritic cells), HbA1c and daily insulin dose at baseline and at 6 and 12 months after T1D diagnosis. A mixed meal tolerance test was administered to each of the subjects 12 months after diagnosis, and the C-peptide area under the curve (AUC) was noted and was then tested for association with all immunological parameters. A gradual decrease in leukocytes (adjusted p = 0.0012) was reflected in a significant decrease in neutrophils (adjusted p = 0.0061) over the post-onset period, whereas Tregs (adjusted p = 0.0205) and originally low pDCs (adjusted p

Background In patients with gout, the serum uric acid (SUA) is usually lower during acute gouty attacks than during intercritical periods. In a previous study, we have shown that abrogation of systemic inflammation by TNF inhibitors (TNFi) results in an increase in the levels of SUA in patients with systemic rheumatic diseases. We have not found any correlation between the magnitude of change of SUA and CRP or pro-inflammatory cytokines (MCP-1, IFN-α2, IFN-γ, Il-1β, IL-6, IL-8, IL-10, IL-12, IL-17a, IL-18, IL-23, IL-33, TNF-α).1 Another possible mechanism for the lowering of SUA during inflammation may be consumption of circulating SUA in free radical reactions generated during systemic inflammation. Allantoin has been validated as a stable biomarker of oxidative stress in humans.2 Objectives We aimed to investigate whether the magnitude of change of SUA after starting therapy with TNFi is associated with the change of oxidative stress marker – allantoin in patients with systemic autoimmune rheumatic diseases: rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA) and juvenile idiopathic arthritis (JIA). Methods A cohort of 94 patients with clinically active chronic inflammatory rheumatic diseases (31 with RA, 33 with AS, 18 with PsA, 12 with JIA) and CRP > 10 mg/L was recruited in the Institute of Rheumatology, Prague. SUA, CRP and allantoin were measured before and after 3 months of treatment with TNFi. Assessment of allantoin in plasma samples was carried out on the Agilent Infinity 1290 system coupled with a Triple Quad 6460 tandem mass spectrometer. For the statistical analysis the ratio between the values at the baseline and values after 3 months of therapy with TNFi were used. We retrieved demographic data and disease characteristics. Results The levels of SUA have significantly increased after 3 months of treatment with TNFi (270.5 [78.8] vs. 303.0 [101.5] μmol/l, p Conclusion The abrogation of systemic inflammation by TNFi results in an increase in the levels of SUA in patients with systemic rheumatic diseases, but the mechanism remains elusive. We have not observed any correlation between the magnitude of change of SUA and CRP or oxidative stress marker allantoin. References [1] Petru L, Hulejova H, Mahajan A, et al. SAT0366 Serum uric acid increases after abrogation of systemic inflammation by TNF inhibition. Annals of the Rheumatic Diseases2018;77:1047 [2] Marrocco I, Altieri F, Peluso I. Measurementand Clinical Significance of Biomarkers of Oxidative Stress in Humans. Oxidative medicine and cellular longevity2017;2017:6501046 Acknowledgement This work was supported by the Charles University research grant GA UK No.940517, by the Ministry of Health, Czech Republic (Institute of Rheumatology - project for conceptual development of a research organisation, 00023728) and by the Czech Science Foundation, Grant No 19-18005Y. Disclosure of Interests Lenka Hasikova: None declared, Marketa Pavlikova: None declared, Petr Kozlik: None declared, Kveta Kalikova: None declared, Blanka Stiburkova: None declared, Jakub Zavada Consultant for: Genzyme-Sanofi, Glaxo, Pfizer, Abbvie, Speakers bureau: Novartis, Sandoz, Biogen

Objectives: The Czech National Childhood Diabetes Register (ČENDA) is a web-based nationwide database that collects treatment and outcome data in children and adolescents with diabetes. Here we present data from the first five years of ČENDA (2013-2017). Methods: Data include characteristics of disease onset and annual summaries of key clinical care parameters from every patient treated by participating pediatric diabetes outpatient clinics. Results: The database contains data from 4361 children (aged 0 to 19 years) from 52 centers, which is estimated to be 85% of all Czech pediatric patients. Of these, 94% had type 1 diabetes (T1D), 4.5% had genetically proven monogenic or secondary, and 1.5% had type 2 diabetes. In children with T1D, median HbA1c decreased throughout the observed period from 66.3 to 61.0 mmol/mol (p < 0.0001, 95% confidence interval for change -6 to -5). Consequently, the proportion of children reaching the ADA target therapeutic goal of 58.5 mmol/mol increased from 28% in 2013 to 40% in 2017. This improvement was significant for all categories of age and diabetes duration and was independent of gender. The overall proportion of children treated with continuous subcutaneous insulin infusion (CSII) remained stable over the observed period (25%). The main predictors associated with lower HbA1c were treatment with CSII, male sex and care provided at a large diabetes center (with >100 patients in regular care). Conclusions: A significant continuous decrease in HbA1c was observed in Czech children over the past five years. As this improvement was not accompanied by appreciable changes in the mode of therapy, we assume that the establishment of our nationwide register has itself constituted a stimulus towards improvement in the care process. Disclosure Z. Sumnik: None. M. Pavlíková: None. O. Cinek: None. Funding Ministry of Health of the Czech Republic

In patients with gout, the serum uric acid (SUA) is usually lower during acute gouty attacks than during intercritical periods. It has been suggested that systemic inflammatory response can cause this phenomenon. The objective is to determine whether therapy with TNF inhibitors (TNFis) affects SUA levels in patients with systemic autoimmune rheumatic diseases (SARDs) and whether SUA changes correlate with pro-inflammatory cytokines or with the oxidative stress marker allantoin. In this study, SUA, CRP, creatinine, MCP-1, IFN-α2, IFN-γ, Il-1β, IL-6, IL-8, IL-10, IL-12, IL-17a, IL-18, IL-23, IL-33, TNF-α, and allantoin levels were measured prior to and after 3 months of TNFis treatment in patients with SARDs. The values obtained in the biochemical assays were then tested for associations with the patients’ demographic and disease-related data. A total of 128 patients (rheumatoid arthritis, n = 44; ankylosing spondylitis, n = 45; psoriatic arthritis, n = 23; and adults with juvenile idiopathic arthritis, n = 16) participated in this study. Among the entire patient population, SUA levels significantly increased 3 months after starting treatment with TNFis (279.5 [84.0] vs. 299.0 [102.0] μmol/l, p

Background ABCG2 is a high-capacity urate transporter that plays a crucial role in renal urate overload and extra-renal urate underexcretion. Previous studies have suggested an association between hyperuricemia and gout susceptibility relative to dysfunctional ABCG2 variants, with rs2231142 (Q141K) being the most common. In this study, we analyzed the ABCG2 gene in a hyperuricemia and gout cohort focusing on patients with pediatric-onset, i.e., before 18 years of age. Method The cohort was recruited from the Czech Republic (n = 234) and consisted of 58 primary hyperuricemia and 176 gout patients, with a focus on pediatric-onset patients (n = 31, 17 hyperuricemia/14 gouts); 115 normouricemic controls were used for comparison. We amplified, sequenced, and analyzed 15 ABCG2 exons. The chi-square goodness-of-fit test was used to compare minor allele frequencies (MAF), and the log-rank test was used to compare empirical distribution functions. Results In the pediatric-onset cohort, two common (p.V12M, p.Q141K) and three very rare (p.K360del, p.T421A, p.T434M) allelic ABCG2 variants were detected. The MAF of p.Q141K was 38.7% compared to adult-onset MAF 21.2% (OR = 2.4, P = 0.005), to the normouricemic controls cohort MAF 8.5% (OR = 6.8, P

Background: Gout and diabetes mellitus type 2 (DM) are frequently co-existing. Metformin is the first choice of treatment for patients with DM type 2, and might – based on previous studies - have beneficial clinical effects on gout through a putative anti-inflammatory as well as serum uric acid (SUA) lowering effect. 1,2,3 Objectives: To investigate the anti-inflammatory and SUA lowering effect of metformin in patients with gout starting uric acid lowering treatment (ULT). Methods: Patients with clinical diagnosis of gout, a first outpatient visit between January 2010 and March 2018 and a follow-up of at least 6 months were included in a retrospective cohort study, conducted in two rheumatology centres in the Netherlands. From this cohort patients with DM starting ULT were selected. Patients with metformin use were compared to patients using other or no antidiabetic medication (control group). Metformin use was defined as use ≥80% of the time during the first six months after initiation of ULT. To evaluate the anti-inflammatory effect, the differences in incidence density (ID) of gout flares in the first six months after starting ULT was measured and analysed using Poisson regression. To evaluate the SUA lowering effect, the difference in baseline SUA, proportion of patients reaching target serum uric acid (SUA Results: Of 2108 gout patients, 309 patients who started ULT also had DM, with 155 in the metformin group and 154 in the control group (table 1). ID of flares was 2.8 and 3.3 per patient year in the control and metformin group respectively, resulting in an incidence rate ratio of 0.93 (95% CI 0.75 – 1.15). SUA levels at baseline were similar, between the two groups (Table 1, p=0.31). At six months 46.1% and 57.4% reached target SUA in the control and metformin group respectively, odds ratio of 1.30 (95%CI 0.80 – 2.08). No difference was found in allopurinol dose at time of reaching target SUA between the groups (1.14 mg, 95% CI -38.89 – 41.19). Conclusion: In contrast to a previous report1, in this study in patients with DM and gout and starting ULT, metformin does not have a clinically relevant added anti-inflammatory or urate lowering effect. References: [1]Vazirpanah N et al. Ann Rheum Dis. 2019;78(5):663-71. [2]Simao AN et al. Expert opinion on therapeutic targets. 2012;16(12):1175-87. [3]Barskova VG et al. Klin Med (Mosk). 2009;87(7):41-6. Disclosure of Interests: : Frouwke Veenstra: None declared, L.M. Verhoef: None declared, Merel Opdam: None declared, Alfons den Broeder: None declared, Wing-Yee Kwok: None declared, Inger Meek: None declared, Frank van den Hoogen: None declared, Marcel Flendrie Grant/research support from: M. Flendrie has received grants from Menarini and Grunenthal. , Consultant of: M. Flendrie has received consultancy fees from Menarini and Grunenthal., Noortje van Herwaarden: None declared

A high-quality research identifying the best physiotherapeutic approach for the improvement of balance in people with multiple sclerosis is missing. This study compared aspects of balance improvement such as therapy specificity to balance, therapy method and category, country, intensity and medical conditions.A multicentric randomised rater-blinded controlled trial comprised three different physiotherapy programs (Czech and Italian outpatient or inpatient programs). All patients received 20 therapy sessions. Experimental group underwent balance specific physiotherapy (it was Motor Program Activating Therapy in the Czech cohort and Sensory-motor Integration Training in the Italian cohort), control group underwent non-balance specific physiotherapy (it was Vojta reflex locomotion in the Czech cohort and conventional dynamic strengthening exercises in the Italian cohort, respectively). Static balance was evaluated by Berg Balance Scale and dynamic balance was assessed by Timed Up-and-Go Test.A total of 149 patients entered the study. Physiotherapy significantly improved static balance (p 0.0001, increase by mean 2.6 points (95% confidence interval 2.0-3.5) in BBS score). Balance specific approach had a higher effect than non-specific balance approach (increase in BBS by 1.9 points, 95% confidence interval 0.9-3.7 points). The intensity of the physiotherapy significantly influenced static balance (BBS by 2.7 points higher in the inpatient setting, p= 0.007). Dynamic balance was also improved (TUG decrease by -0.8 s (95% CI -1.4 - -0.1s, p = 0.011)); the balance specificity had no impact. The level of disability played the most important role (p= 0.022).Although the overall changes in static and dynamic balance were statistically significant, they were quite small in a clinical sense. A small statistically significant difference between balance specific and non-specific treatment was found. It seems that a high intensity of the therapy is critical to maximize the effectiveness.

Background A wide variety of interventions exists in physical therapy (PT), but knowledge about their use across different geographical regions is limited. This study investigated the use of PT interventions in people with Multiple Sclerosis (MS) across Europe. It aimed to determine whether regions differ in applying interventions, and explore whether factors other than regions play a role in their use. Methods In an online cross-sectional survey, 212 respondents from 115 European workplaces providing PT services to people with MS representing 26 countries (four European regions) participated. Cluster analysis, Pearson Chi-squared test and a Poisson regression model were used to analyze the data. Results Thirteen of 45 listed PT interventions were used by more than 75% of centers, while nine interventions were used by less than 25%. For 12 interventions, regions differed markedly in their use. Cluster analysis of centers identified four clusters similar in their intervention use. Cluster assignment did not fully align with regions. While center region was important, center size, number and gender of physical therapists working in the center, and time since qualification also played a role. Cluster analysis exploring the use of the interventions provided the basis for a categorization of PT interventions in line with their primary focus: 1. Physical activity (fitness/endurance/resistance) training; 2. Neuroproprioceptive "facilitation/inhibition"; 3. Motor/skill acquisition (individualized therapy led); 4. Technology based interventions. Conclusions To our knowledge this is the first study that has explored this topic in MS. The results broaden our understanding of the different PT interventions used in MS, as well as the context of their use.

Objectives Common dysfunctional variants of ATP binding cassette subfamily G member 2 (Junior blood group) (ABCG2), a high-capacity urate transporter gene, that result in decreased urate excretion are major causes of hyperuricemia and gout. In the present study, our objective was to determine the frequency and effect on gout of common and rare non-synonymous and other functional allelic variants in the ABCG2 gene. Methods The main cohort recruited from the Czech Republic consisted of 145 gout patients; 115 normouricaemic controls were used for comparison. We amplified, directly sequenced and analysed 15 ABCG2 exons. The associations between genetic variants and clinical phenotype were analysed using the t-test, Fisher's exact test and a logistic and linear regression approach. Data from a New Zealand Polynesian sample set and the UK Biobank were included for the p.V12M analysis. Results In the ABCG2 gene, 18 intronic (one dysfunctional splicing) and 11 exonic variants were detected: 9 were non-synonymous (2 common, 7 rare including 1 novel), namely p.V12M, p.Q141K, p.R147W, p.T153M, p.F373C, p.T434M, p.S476P, p.D620N and p.K360del. The p.Q141K (rs2231142) variant had a significantly higher minor allele frequency (0.23) in the gout patients compared with the European-origin population (0.09) and was significantly more common among gout patients than among normouricaemic controls (odds ratio = 3.26, P < 0.0001). Patients with non-synonymous allelic variants had an earlier onset of gout (42 vs 48 years, P = 0.0143) and a greater likelihood of a familial history of gout (41% vs 27%, odds ratio = 1.96, P = 0.053). In a meta-analysis p.V12M exerted a protective effect from gout (P < 0.0001). Conclusion Genetic variants of ABCG2, common and rare, increased the risk of gout. Non-synonymous allelic variants of ABCG2 had a significant effect on earlier onset of gout and the presence of a familial gout history. ABCG2 should thus be considered a common and significant risk factor for gout.

Gout is an inflammatory arthritis influenced by environmental risk factors and genetic variants. The common dysfunctional p.Q141K allele of the ABCG2 gene affects gout development. We sought after the possible association between the p.Q141K variant and gout risk factors, biochemical, and clinical determinants in hyperuricemic, gouty, and acute gouty arthritis cohorts. Further, we studied the correlation of p.Q141K allele and levels of pro-/anti-inflammatory cytokines. Coding regions of the ABCG2 gene were analyzed in 70 primary hyperuricemic, 182 gout patients, and 132 normouricemic individuals. Their genotypes were compared with demographic and clinical parameters. Plasma levels of 27 cytokines were determined using a human multiplex cytokine assay. The p.Q141K variant was observed in younger hyperuricemic/gout individuals (p = 0.0003), which was associated with earlier disease onset (p = 0.004), trend toward lower BMI (p = 0.056), and C-reactive protein (CRP, p = 0.007) but a higher glomerular filtration rate (GFR, p = 0.035). Levels of 19 cytokines were higher, mainly in patients with acute gouty arthritis (p < 0.001), irrespective of the presence of the p.Q141K variant. The p.Q141K variant influences the age of onset of primary hyperuricemia or gout and other disease-linked risk factors and symptoms. There was no association with cytokine levels in the circulation.

ATP-binding cassette subfamily G member 2 (ABCG2) is a physiologically important urate transporter. Accumulating evidence demonstrates that congenital dysfunction of ABCG2 is an important genetic risk factor in gout and hyperuricemia, recent studies suggest the clinical significance of both common and rare variants of ABCG2. However, the effects of rare variants of ABCG2 on the risk of such diseases are not fully understood. Here, using a cohort of 250 Czech individuals of European descent (68 primary hyperuricemia patients and 182 primary gout patients), we examined exonic non-synonymous variants of ABCG2. Based on the results of direct sequencing and database information, we experimentally characterized nine rare variants of ABCG2: R147W (rs372192400), T153M (rs753759474), F373C (rs752626614), T421A (rs199854112), T434M (rs769734146), S476P (not annotated), S572R (rs200894058), D620N (rs34783571), and a three-base deletion K360del (rs750972998). Functional analyses of these rare variants revealed a deficiency in the plasma membrane localization of R147W and S572R, lower levels of cellular proteins of T153M and F373C, and null urate uptake function of T434M and S476P. Accordingly, we newly identified six rare variants of ABCG2 that showed lower or null function. Our findings contribute to deepening the understanding of ABCG2-related gout/hyperuricemia risk and the biochemical characteristics of the ABCG2 protein.

The role of folates as coenzymes in 1-carbon metabolism and the clinical consequences of disturbed folate metabolism are widely known. Folate status is a complex trait determined by both exogenous and endogenous factors. This study analyzed the association between 12 genetic variants and folate status in a Czech population with no folate fortification program. These 12 genetic variants were selected from 56 variant alleles found by resequencing the coding sequences and adjacent intronic regions of 6 candidate genes involved in folate metabolism or transport (FOLR1, FOLR2, FOLR3, MTHFR, PCFT, and RFC) from 29 individuals with low plasma and erythrocyte folate concentrations. Regression analyses of a cohort of 511 Czech controls not taking folate supplements revealed that only 2 variants in the MTHFR gene were associated with altered folate concentrations in plasma and/or erythrocytes. In our previous study, we observed that the common variant MTHFR c.665C > T (known as c.677C > T; p.A222V) was associated with decreased plasma folate concentrations. In the present study, we show in addition that the rare variant MTHFR c.1958C > T (p.T653M) is associated with significantly increased erythrocyte folate concentrations (P = 0.02). Multivariate regression analysis revealed that this uncommon variant, which is present in 2% of Czech control chromosomes, explains 0.9% of the total variability of erythrocyte folate concentrations; the magnitude of this effect size was comparable with that of the common MTHFR c.665C > T variant. This result indicates that the rare genetic variants may determine folate status to a similar extent as the common allelic variant.

Polypropylene meshes are frequently used in abdominal and vaginal reconstructive surgery. Recently, several authors have claimed that mesh-associated complications may be linked to mesh shrinkage. We have performed a prospective study with postoperative follow-up by ultrasound examination at two time points after Prolift anterior implantation to assess changes in the ultrasound appearance of mesh implants over time. We assessed 36 patients who had undergone mesh implantation with Prolift anterior™ mesh for the correction of symptomatic anterior vaginal wall prolapse. During the surgery, we measured the actual midline length of the mesh (initial length). On the fourth postoperative day, we performed a vaginal ultrasound examination (US) to measure mesh length in the midsagittal plane. A second US was performed 3–5 months after surgery to repeat this measurement. There was a significant difference in mesh length determined before and 4 days after surgery (90.3 vs. 57.1 mm, P =

The hypotheses of this study were that the TVT-SECUR procedure restricts urethral mobility, which leads to a greater likelihood of curative effect, and that the restriction might change over time.Analyses of the position of the urethra and the tape of 85 patients who underwent the TVT-S procedure were performed using perineal ultrasonography. The efficacy of the TVT-S procedure was evaluated by cough test and by the questionnaire ICIQ-UI SF.Objectively, 53/85 (62%) of patients had a negative cough test, and in 32/85 (38%) of patients leakage of urine persisted. The TVT-S procedure restricts urethral mobility, and a higher degree of obstruction is associated with a higher likelihood of cure. The restriction weakens within the first 3 months after surgery.The objective cure rate of TVT-S procedure is low irrespective of placement technique. This may be due to insufficient restriction of urethral mobility.

We have identified 21 different alpha-galactosidase A gene (GLA) mutations in 22 unrelated Czech and Slovak families with Fabry disease. Eleven of these mutations were novel (point mutations D93N, A135V, D155H, G171R, Q280K, G360S, Q330X, splicing errors c.194ins14, c.801ins36 and deletions c.674_732del59, g.3405_6021del2617). Genotyping of family members for family-specific mutations revealed 55 heterozygotes that manifested clinical symptoms of different severity. To examine the contribution of X-inactivation skewing to disease manifestation in Fabry heterozygotes, we have adopted the Mainz severity scoring scheme and compared the score values with the X-inactivation status in 39 carriers in an age-dependent manner. The age-score trendline of Fabry females who had a predominantly inactivated X-chromosome bearing a wild-type GLA allele (10 of 38 females) was markedly steeper than in the rest of the cohort. One female carrier with an inactivated mutated allele had a low score value when compared to the other heterozygotes of the same age. These data suggest that X-inactivation is indeed a major factor determining the severity of clinical involvement in Fabry heterozygotes. There was a statistically significant difference between the severity score values of heterozygotes with random and non-random X-chromosome inactivation at the 5% level of significance. Further studies will show if the degree of the wildtype allele inactivation will be useful as a predictive marker of severity of phenotype in Fabry heterozygotes. Although the correlation between X-inactivation skewing and presentation of the disease in Fabry heterozygotes has previously been suggested in the literature, this report is among the first attempts to examine this relationship systematically.

Objective Uric acid is the end product of purine metabolism in humans, and increased serum uric acid concentrations lead to gout. The objective of the current study was to identify factors that are independently associated with serum uric acid concentrations in a cohort of Czech control individuals. Methods The cohort consisted of 589 healthy subjects aged 18–65 years. We studied the associations between the serum uric acid concentration and the following: (i) demographic, anthropometric and other variables previously reported to be associated with serum uric acid concentrations; (ii) the presence of metabolic syndrome and the levels of metabolic syndrome components; and (iii) selected genetic variants of the MTHFR (c.665C>T, c.1286A>C), SLC2A9 (c.844G>A, c.881G>A) and ABCG2 genes (c.421C>A). A backward model selection procedure was used to build two multiple linear regression models; in the second model, the number of metabolic syndrome criteria that were met replaced the metabolic syndrome-related variables. Results The models had coefficients of determination of 0.59 and 0.53. The serum uric acid concentration strongly correlated with conventional determinants including male sex, and with metabolic syndrome-related variables. In the simplified second model, the serum uric acid concentration positively correlated with the number of metabolic syndrome criteria that were met, and this model retained the explanatory power of the first model. Moderate wine drinking did not increase serum uric acid concentrations, and the urate transporter ABCG2, unlike MTHFR, was a genetic determinant of serum uric acid concentrations. Conclusion Metabolic syndrome, moderate wine drinking and the c.421C>A variant in the ABCG gene are independently associated with the serum uric acid concentration. Our model indicates that uric acid should be clinically monitored in persons with metabolic syndrome.

ObjectiveUsing European descent Czech populations, we performed a study of SLC2A9 and SLC22A12 genes previously identified as being associated with serum uric acid concentrations and gout. This is the first study of the impact of non-synonymous allelic variants on the function of GLUT9 except for patients suffering from renal hypouricemia type 2.MethodsThe cohort consisted of 250 individuals (150 controls, 54 nonspecific hyperuricemics and 46 primary gout and/or hyperuricemia subjects). We analyzed 13 exons of SLC2A9 (GLUT9 variant 1 and GLUT9 variant 2) and 10 exons of SLC22A12 by PCR amplification and sequenced directly. Allelic variants were prepared and their urate uptake and subcellular localization were studied by Xenopus oocytes expression system. The functional studies were analyzed using the non-parametric Wilcoxon and Kruskall-Wallis tests; the association study used the Fisher exact test and linear regression approach.ResultsWe identified a total of 52 sequence variants (12 unpublished). Eight non-synonymous allelic variants were found only in SLC2A9: rs6820230, rs2276961, rs144196049, rs112404957, rs73225891, rs16890979, rs3733591 and rs2280205. None of these variants showed any significant difference in the expression of GLUT9 and in urate transport. In the association study, eight variants showed a possible association with hyperuricemia. However, seven of these were in introns and the one exon located variant, rs7932775, did not show a statistically significant association with serum uric acid concentration.ConclusionOur results did not confirm any effect of SLC22A12 and SLC2A9 variants on serum uric acid concentration. Our complex approach using association analysis together with functional and immunohistochemical characterization of non-synonymous allelic variants did not show any influence on expression, subcellular localization and urate uptake of GLUT9.

Background and objectives B-cell activating factor of the TNF family (BAFF) plays a role in (auto)antibody production. Elevated serum levels (sBAFF) were found in patients with myositis. Associations of elevated sBAFF with a SNP in the 5´regulatory region of the BAFF genewere reported in patients with autoimmune diseases, together with TTTT haplotype of the four SNPs located upstream of the BAFF gene. TTTT was associated with myositis in Czech patients, independently from the HLA-DRB1*03 allele. Here we evaluate associations of sBAFF with particular SNPs, anti-Jo-1-autoantibodies, HLA-DRB1*03, ILD and disease activity in myositis. Materials and methods The SNPs (rs9514828:871C>T, rs9514827:-2841T>C, rs3759467:-2704T>C and rs1041569:-2701T >A) were analysed by direct DNA sequencing in 311 patients with myositis (age:58.0 ± 14.5(years), females = 74%) and 113 healthy controls (age:40.6 ± 14.3, females = 70%). Levels of sBAFF were measured by ELISA. Autoantibodies were detected by immunoprecipitation. Multivariable logistic regression model for presence of anti-Jo-1-autoantibodies and nonparametric tests for group comparisons and correlation analysis were used. Results Analysed patients cohort included 150 DM, 139 PM, 51% ILD and 24% anti-Jo-1-positive patients. HLA-DRB1*03 was present in 45% of patients and 16% of controls. Higher s-BAFF levels were detected in: patients compared to healthy controls (p Logistic regression model explaining 49% (McFadden R 2 =0.49) of the data variability included, besides ILD (OR = 27.24;p 2 = 0.38). However, the additive effect of -871T allele to sBAFF levels in anti-Jo-1-positive patients compared to autoantibody-negative (higher in -871TT:p = 0.023 and -871CT:p = 0.043) and the opposite association in -2841TT genotype (higher in -2841CC: p = 0.033 and -2841CT:p = 0.068)were seen. Conclusion In addition to ILD and HLA-DRB1*03 allele, SNPs of the promotor region of the BAFF gene, -871C >T and -2841T >C, increase the risk of having anti-Jo-1-autoantibodies and high sBAFF levels in patients with myositis. Acknowledgements MZCR-Institutional support of research organisation-00023728.

Objective The aim of this study is to present our first experience with a novel modification of the tension-free sling idea and to evaluate the safety and efficacy of this new procedure for the treatment of stress urinary incontinence in women. Study design Eighty-five women with previously untreated stress urinary incontinence were recruited to participate in a clinical study. The efficacy of this surgical procedure was evaluated perioperatively and 3 months (±1 week) after operation—objectively by cough test and subjectively by the questionnaires Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire and the International Consultation on Incontinence Questionnaire-Short Form. All data were processed and statistical analyses performed in statistical environment R, version 2.5.1. Results From our results we conclude that there were no perioperative complications, objectively 62% of these patients were completely dry and 25% of patients improved. We observed a higher proportion of vaginal wall erosion (7/85) and urgency de novo (5/85) in the learning period group with respect to the routine period group. Conclusions Our first experience with the tension-free vaginal tape secur system procedure is that it has a low percentage of perioperative complications. The learning curve has to be taken in account with reference to postoperative complications.

Objectives To evaluate changes in the mobility of the whole urethra, in the proximal urethra (funneling) and in the thickness of the urinary bladder wall, after a successful tension-free vaginal tape (TVT) procedure. Methods This prospective longitudinal study included 52 women with urodynamically confirmed stress urinary incontinence who had undergone a successful TVT procedure. Ultrasound examination was performed before the TVT procedure and at a median of 3 (range, 3–6) months after surgery. For all women, the changes to the urethra and urinary bladder induced by surgery were examined. For three mobility groups (low, intermediate and high urethral mobility before surgery) we compared the changes induced by the operation and the typical position and mobility of the tape. Results The position of the urethra at rest was not influenced by surgery. The operation significantly decreased the mobility of all parts of the urethra during Valsalva. The absolute changes of the vector of the urethral movement differed according to the mobility group (average decrease, 6 mm; decrease for women with low, intermediate and high mobility, respectively, 2–3 mm, 4–6 mm and 9 mm). The change in relative mobility was the same in all groups. The operation decreased funneling (width and depth) during maximal Valsalva. After surgery there was an increase in the thickness of the bladder wall (by 0.64 and 0.73 mm, respectively, at the anterior part and trigone). Conclusions A successful TVT procedure did not influence the position of the urethra at rest but significantly decreased the mobility of the urethra during Valsalva and also decreased funneling at maximal Valsalva. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.

The aims of the present study were to find the correlation between Valsalva leak-point pressure (VLPP) and cough leak-point pressure (CLPP) and to determine whether the water perfusion maximum urethral closure pressure (MUCP) correlates with VLPP. Seventy-nine women with previously untreated stress urinary incontinence were recruited to participate in a clinical study. Their mean age was 56.4 years, mean BMI was 27.8, and mean parity was 1.9. The mean values of VLPP and CLPP were 50.4 and 52.9 cm H(2)O, respectively. We did not find statistically significant differences in the mean values of VLPP and CLPP. The mean value of MUCP at rest was 44.2 cm H(2)O and the mean value of MUCP during maximal Valsalva maneuver was 37.2 cm H(2)O; with 500 ml of sterile saline in the bladder the difference between them is statistically significant. In the study group (n=79), 56 patients (77%) had low VLPP (or =60 cm H(2)O), 21 patients (30%) had low MUCP (or =30 cm H(2)O), and 8 patients had MUCPor =20 cm H(2)O (all at rest). Of the 56 patients with low VLPP, 16 also had a low MUCP (or =30 cm H(2)O). This study mainly compares two parameters-the MUCP and the VLPP. Based on our results we can conclude that there is no correlation between these parameters. MUCP measures urethral resistance at rest and VLPP measures urethral resistance during increased intra-abdominal pressure (Valsalva maneuver).