First 2 cases with thiamine-responsive megaloblastic anemia in the Czech Republic, a rare form of monogenic diabetes mellitus: a novel mutation in the thiamine transporter SLC19A2 gene-intron 1 mutation c.204+2T>G.

Thiamine-responsive megaloblastic anemia (TRMA) is a rare autosomal recessive disorder caused by mutations in the SLC19A2 gene. To date at least 43 mutations have been reported for the gene encoding a plasma membrane thiamine transporter protein (THTR-1). TRMA has been reported in less than 80 cases worldwide. Here, we illustrate 2 female patients with TRMA first diagnosed in the Czech Republic and in central Europe being confirmed by sequencing of the THTR-1 gene SLC19A2. Both subjects are compound heterozygotes with 3 different mutations in the SLC19A2 gene. In case 2, the SLC19A2 intron 1 mutation c.204+2T>G has never been reported before. TRMA subjects are at risk of diabetic ketoacidosis during intercurrent disease and arrythmias. Thiamine supplementation has prevented hematological disorders over a few years in both pediatric subjects, and improved glycaemic control of diabetes mellitus. Patient 1 was suffering from hearing loss and rod-cone dystrophy at the time of diagnosis, however, she was unresponsive to thiamine substitution. Our patient 2 developed the hearing loss despite the early thiamine substitution, however no visual disorder had developed. The novel mutation described here extends the list of SLC19A2 mutations causing TRMA.

Paediatric Rome III Criteria-Related Abdominal Pain Is Associated With Helicobacter pylori and Not With Calprotectin.

OBJECTIVES: Abdominal pain-related functional gastrointestinal disorders in children include functional dyspepsia, functional abdominal pain, irritable bowel syndrome, and abdominal migraine. We aimed to evaluate a possible association between functional abdominal pain disorders and Helicobacter pylori infection and faecal calprotectin level. METHODS: Prospective observational study including consecutive children with functional gastrointestinal disorders fulfilling Rome III criteria (cases) and age/sex-matched healthy controls. H pylori has been detected by biopsy-based tests and stool-antigen detection, faecal calprotectin by enzyme-linked immunosorbent assay. RESULTS: A total of 56 cases (27 with functional dyspepsia) and 56 controls were enrolled. H pylori being detected in 17 of 56 cases (30.4%) and 4 of 56 controls (7.1%, odds ratio: 5.7; 95% confidence interval [CI]: 1.8-18.2, P = 0.003). H pylori was detected significantly more frequently in cases with functional dyspepsia (14/27, 51.9% odds ratio: 14.0; 95% CI: 3.9-49.7, P = 0.00001) than in controls and not in cases with other well-recognized functional gastrointestinal complaints (3/29, 10.3%). The median faecal calprotectin level was similar in cases (7.8 µg/g, 95% CI: 7.8-8.4) including those with gastritis, and controls (9.1 µg/g, 95% CI: 7.8-11.3). Gastritis features were more frequent in H pylori-infected and noninfected cases with functional dyspepsia (27/27, 100%) than in cases with other abdominal functional complaints (15/29, 51.7%, P = 0.007). CONCLUSIONS: H pylori gastritis and noninfectious gastritis were associated with functional dyspepsia in children referred for abdominal pain-related functional gastrointestinal disorders while faecal calprotectin is not a predictor of gastritis and is similar in children with functional abdominal pain symptoms and in controls.

Weld size and resistance in rectangular hollow section T-joints.

When chord face failure occurs, one of the factors, which influence the resistance of the square hollow sections joint is the brace-to-chord width ratio of the joint. This includes the size of the weld connecting the two members. The influence of weld type and weld size on the behaviour of rectangular and square hollow section joints was studied at the Czech Technical University in Prague. This paper describes an experimental and numerical investigation of square hollow section joints. The welded T-joints were loaded by axial compression. Three different types of welds were investigated - butt welds, fillet welds and a combination of these types. Experimental results for the T-joint together with material characteristics are provided. The paper presents a validation of the numerical model to experimental data. The research-oriented model with shell elements, prepared in RFEM finite element software, represents well the behaviour of square and rectangular hollow section joints. A parametric study with a broader range of sections was performed using the design-oriented shell elements model. Based on the results of the experimental and numerical investigations a modification of the analytical equations used in current prEN1993-1-8:2021 is proposed.

Pregnancy Termination and Postnatal Major Congenital Heart Defect Prevalence After Introduction of Prenatal Cardiac Screening.

Importance: Prenatal cardiac screening of the first and second trimesters has had a major impact on postnatal prevalence of congenital heart defects (CHDs), rates of termination of pregnancy (TOP), and outcomes among children born alive with CHDs. Objective: To examine the prenatal and postnatal incidence of major CHDs (ie, necessitating intervention within the first year of life), detection rate trends, rates of TOP, and the association of cardiac screening with postnatal outcomes. Design, Settings, and Participants: In this cross-sectional study, 3827 fetuses with antenatally diagnosed major CHDs in the Czech Republic (population 10.7 million) between 1991 and 2021 were prospectively evaluated with known outcomes and associated comorbidities. Prenatal and postnatal prevalence of CHD in an unselected population was assessed by comparison with a retrospective analysis of all children born alive with major CHDs in the same period (5454 children), using national data registry. Data analysis was conducted from January 1991 to December 2021. Main Outcomes and Measures: Prenatal detection and postnatal prevalence of major CHDs and rate of TOPs in a setting with a centralized health care system over 31 years. Results: A total of 3 300 068 children were born alive during the study period. Major CHD was diagnosed in 3827 fetuses, of whom 1646 (43.0%) were born, 2069 (54.1%) resulted in TOP, and 112 (2.9%) died prenatally. The prenatal detection rate increased from 6.2% in 1991 to 82.8% in 2021 (P < .001). Termination of pregnancy decreased from 70% in 1991 to 43% (P < .001) in 2021. Of 627 fetuses diagnosed in the first trimester (introduced in 2007), 460 were terminated (73.3%). Since 2007, of 2066 fetuses diagnosed in the second trimester, 880 (42.6%) were terminated, resulting in an odds ratio of 3.6 (95% CI, 2.8-4.6; P < .001) for TOP in the first trimester compared with the second trimester. Postnatal prevalence of major CHDs declined from 0.21% to 0.14% (P < .001). The total incidence (combining prenatal detection of terminated fetuses with postnatal prevalence) of major CHD remained at 0.23% during the study period. Conclusions and Relevance: In this cross-sectional study, the total incidence of major CHD did not change significantly during the 31-year study period. The prenatal detection of major CHD approached 83% in the current era. Postnatal prevalence of major CHD decreased significantly due to early TOPs and intrauterine deaths. The introduction of first trimester screening resulted in a higher termination rate in the first trimester but did not revert the overall decreasing trend of termination for CHDs in general.

Bronchial Asthma as a Cardiovascular Risk Factor: A Prospective Observational Study.

Introduction: Asthma as a chronic inflammatory disorder has been suggested as a risk factor for endothelial dysfunction (ED), but studies on the association between asthma and cardiovascular disease (CVD) risk are limited. Background: We assessed associations of ED with the severity of asthma, eosinophilic inflammation, lung function, and asthma control. Methods: 52 young asthmatics (median age of 25.22 years) and 45 healthy individuals were included. Demographic, clinical, and laboratory findings were recorded. We evaluated microvascular responsiveness by recording the reactive hyperemia index (RHI) indicating post-occlusive peripheral endothelium-dependent changes in vascular tone using the Itamar Medical EndoPAT2000. VCAM-1, ADMA, high-sensitive CRP (hsCRP), and E-selectin were measured. Results: Asthmatics had considerably lower RHI values (p < 0.001) with a dynamic decreasing trend by asthma severity and higher hsCRP levels (p < 0.001). A substantial increase in hsCRP and E-selectin with asthma severity (p < 0.05) was also observed. We confirmed a higher body mass index (BMI) in asthmatics (p < 0.001), especially in women and in severe asthma. Conclusions: We demonstrated the progression of CVD in asthmatics and the association of the ongoing deterioration of ED with the inflammatory severity, suggesting that the increased risk of CVD in young asthmatics is dependent on disease severity. The underlying mechanisms of risk factors for CVD and disease control require further study.

Circulating Serum Cystatin C as an Independent Risk Biomarker for Vascular Endothelial Dysfunction in Patients with COVID-19-Associated Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Observational Study.

INTRODUCTION: Multisystem inflammatory syndrome in children (MIS-C) is a new clinical entity that has emerged in the context of the COVID-19 pandemic. Despite the less severe course of the disease, varying degrees of cardiovascular events may occur in MIS-C; however, data on vascular changes occurring in MIS-C are still lacking. Endothelial dysfunction (ED) is thought to be one of the key risk factors contributing to MIS-C. BACKGROUND: We conducted a prospective observational study. We investigated possible manifestations of cardiac and endothelial involvement in MIS-C after the treatment of the acute stage and potential predictive biomarkers in patients with MIS-C. METHODS: Twenty-seven consecutive pediatric subjects (≥9 years), at least three months post-treated MIS-C of varying severity, in a stable condition, and twenty-three age- and sex-matched healthy individuals (HI), were enrolled. A combined non-invasive diagnostic approach was used to assess endothelial function as well as markers of organ damage using cardiac examination and measurement of the reactive hyperemia index (RHI), by recording the post- to pre-occlusion pulsatile volume changes and biomarkers related to ED and cardiac disease. RESULTS: MIS-C patients exhibited a significantly lower RHI (indicative of more severe ED) than those in HI (1.32 vs. 1.80; p = 0.001). The cutoff of RHI ≤ 1.4 was independently associated with a higher cardiovascular risk. Age and biomarkers significantly correlated with RHI, while serum cystatin C (Cys C) levels were independently associated with a diminished RHI, suggesting Cys C as a surrogate marker of ED in MIS-C. CONCLUSIONS: Patients after MIS-C display evidence of ED, as shown by a diminished RHI and altered endothelial biomarkers. Cys C was identified as an independent indicator for the development of cardiovascular disease. The combination of these factors has the potential to better predict the cardiovascular consequences of MIS-C. Our study suggests that ED may be implicated in the pathophysiology of this disease.

Repeated bedside echocardiography in children with respiratory failure.

BACKGROUND: The aim of this study was to verify the benefits and limitations of repeated bedside echocardiographic examinations in children during mechanical ventilation. For the purposes of this study, we selected the data of over a time period from 2006 to 2010. METHODS: A total of 235 children, average age 3.21 (SD 1.32) years were included into the study and divided into etiopathogenic groups. High-risk groups comprised: Acute lung injury and acute respiratory distress syndrome (ALI/ARDS), return of spontaneous circulation after cardiopulmonary resuscitation (ROSC), bronchopulmonary dysplasia (BPD), cardiomyopathy (CMP) and cardiopulmonary disease (CPD). Transthoracic echocardiography was carried out during mechanical ventilation. The following data were collated for statistical evaluation: right and left ventricle myocardial performance indices (RV MPI; LV MPI), left ventricle shortening fraction (SF), cardiac output (CO), and the mitral valve ratio of peak velocity of early wave (E) to the peak velocity of active wave (A) as E/A ratio. The data was processed after a period of recovery, i.e. one hour after the introduction of invasive lines (time-1) and after 72 hours of comprehensive treatment (time-2). The overall development of parameters over time was compared within groups and between groups using the distribution-free Wilcoxons and two-way ANOVA tests. RESULTS: A total of 870 echocardiographic examinations were performed. At time-1 higher average values of RV MPI (0.34, SD 0.01 vs. 0.21, SD 0.01; p < 0.001) were found in all groups compared with reference values. Left ventricular load in the high-risk groups was expressed by a higher LV MPI (0.39, SD 0.13 vs. 0.29, SD 0.02; p < 0.01) and lower E/A ratio (0.95, SD 0.36 vs. 1.36, SD 0.64; p < 0.001), SF (0.37, SD 0.11 vs. 0.47, SD 0.02; p < 0.01) and CO (1.95, SD 0.37 vs. 2.94, SD 1.03; p < 0.01). At time-2 RV MPI were lower (0.25, SD 0.02 vs. 0.34, SD 0.01; p < 0.001), but remained higher compared with reference values (0.25, SD 0.02 vs. 0.21, SD 0.01; p < 0.05). Other parameters in high-risk groups were improved, but remained insignificantly different compared with reference values. CONCLUSION: Echocardiography complements standard monitoring of valuable information regarding cardiac load in real time. Chest excursion during mechanical ventilation does not reduce the quality of the acquired data.

Healthy lung tissue response to mechanical ventilation in an experimental porcine model.

BACKGROUND: The aim of this comparative study was to assess the impact of two different settings of tidal volume (Vt) on the function and morphology of the mechanically ventilated lungs during a 12-h period. MATERIALS AND METHODS: A total of 32 animals were randomly divided into two groups. Group A included piglets ventilated with a Vt of 6 ml/kg and group B piglets ventilated with a Vt of 10 ml/kg. Lung functions and pulmonary mechanics were evaluated after 1 and 12 h of mechanical ventilation. Morphological changes of the lung tissue were evaluated at the end of the study. RESULTS: Twelve hours of lower Vt ventilation was associated with the development of respiratory acidosis but minimal histological changes. Higher Vt led to pronounced histological changes in terms of proliferation and apoptosis and a decrease of dynamic compliance, with a trend towards lower oxygenation during the study. CONCLUSION: Mechanical ventilation with a Vt of 6 ml/kg induces minimal histological lung parenchymal changes in terms of proliferation and apoptosis. Positive pressure mechanical ventilation with Vt of 10 ml/kg does not protect lung tissue and induces substantial proliferative and apoptotic changes within the lung parenchyma. Positive pressure mechanical ventilation with Vt of 10 ml/kg does not guarantee protection of healthy pulmonary tissue in the absence of a priming pulmonary insult.