B cell phenotype and serum levels of interferons, BAFF, and APRIL in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C).

BACKGROUND: Multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) is a late complication of pediatric COVID-19, which follows weeks after the original SARS-CoV-2 infection, regardless of its severity. It is characterized by hyperinflammation, neutrophilia, lymphopenia, and activation of T cells with elevated IFN-γ. Observing the production of autoantibodies and parallels with systemic autoimmune disorders, such as systemic lupus erythematodes (SLE), we explored B cell phenotype and serum levels of type I, II, and III interferons, as well as the cytokines BAFF and APRIL in a cohort of MIS-C patients and healthy children after COVID-19. RESULTS: We documented a significant elevation of IFN-γ, but not IFN-α and IFN-λ in MIS-C patients. BAFF was elevated in MIS-C patient sera and accompanied by decreased BAFFR expression on all B cell subtypes. The proportion of plasmablasts was significantly lower in patients compared to healthy post-COVID children. We noted the pre-IVIG presence of ENA Ro60 autoantibodies in 4/35 tested MIS-C patients. CONCLUSIONS: Our work shows the involvement of humoral immunity in MIS-C and hints at parallels with the pathophysiology of SLE, with autoreactive B cells driven towards autoantibody production by elevated BAFF.

Nationwide observational study of paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the Czech Republic.

The worldwide outbreak of the novel 2019 coronavirus disease (COVID-19) has led to recognition of a new immunopathological condition: paediatric inflammatory multisystem syndrome (PIMS-TS). The Czech Republic (CZ) suffered from one of the highest incidences of individuals who tested positive during pandemic waves. The aim of this study was to analyse epidemiological, clinical, and laboratory characteristics of all cases of paediatric inflammatory multisystem syndrome (PIMS-TS) in the Czech Republic (CZ) and their predictors of severe course. We performed a retrospective-prospective nationwide observational study based on patients hospitalised with PIMS-TS in CZ between 1 November 2020 and 31 May 2021. The anonymised data of patients were abstracted from medical record review. Using the inclusion criteria according to World Health Organization definition, 207 patients with PIMS-TS were enrolled in this study. The incidence of PIMS-TS out of all SARS-CoV-2-positive children was 0.9:1,000. The estimated delay between the occurrence of PIMS-TS and the COVID-19 pandemic wave was 3 weeks. The significant initial predictors of myocardial dysfunction included mainly cardiovascular signs (hypotension, oedema, oliguria/anuria, and prolonged capillary refill). During follow-up, most patients (98.8%) had normal cardiac function, with no residual findings. No fatal cases were reported.Conclusions: A 3-week interval in combination with incidence of COVID-19 could help increase pre-test probability of PIMS-TS during pandemic waves in the suspected cases. Although the parameters of the models do not allow one to completely divide patients into high and low risk groups, knowing the most important predictors surely could help clinical management.

Ultrasound cardiac output monitoring in mechanically ventilated children.

AIM: To non-invasively identify the hemodynamic changes in critically ill children during the first 48 h following initiation of mechanical ventilation by the ultrasound cardiac output monitor (USCOM) method and compare the data in children with pulmonary and non-pulmonary pathology. MATERIALS AND METHODS: This was a prospective observational study to evaluate the influence of mechanical ventilation on hemodynamic changes and to describe hemodynamic profiles of mechanically ventilated children. A total of 56 children with respiratory failure were included in the present study. Ventilated patients are divided into two groups. Group A (n=36) includes patients with pulmonary pathology. Group B (n=20) consists of patients with extra pulmonary etiology of respiratory failure. Hemodynamic parameters (cardiac index and systemic vascular resistance index) were evaluated using ultrasound cardiac output monitoring (USCOM 1A) immediately following initiation of mechanical ventilation and again at 6, 12, and 48 h. Pharmacological circulatory support (inotropes, vasopressors, levosimendan and phosphodiesterase III inhibitors) was individually and continuously modified based on real-time hemodynamic parameters and optimal fluid balance. RESULTS: No significant differences in hemodynamic profiles were found between Group A and Group B. CONCLUSION: The protective strategy of mechanical ventilation was not associated with significant differences in hemodynamic profiles between children ventilated for pulmonary and non-pulmonary pathologies. CLINICAL SIGNIFICANCE: Hemodynamically unstable children ventilated for pulmonary pathology with the protective strategy of mechanical ventilation had a greater requirement for inotropic and combined inotropic and vasoactive circulatory support than children ventilated for non-pulmonary causes of respiratory failure.

Serious Complications of Intraosseous Access during Infant Resuscitation.

We report on a 2.5-month-old infant with ischemia of the left leg and compartment following intraosseous needle application during resuscitation. Unfortunately, this event led to major limb amputation. The cause, mechanism, and prevention of this severe complication are discussed in this article.

Alcohol and drug intoxications in adolescents admitted to paediatric wards in the Czech Republic: 5-year retrospective study 2006-2010.

OBJECTIVES: The aim of the study was to establish frequency, severity and circumstances of alcohol and drug intoxications in adolescents admitted to inpatient wards in the Czech Republic. METHODS: Chief physician of each participating ward (or their designated deputy) searched the patient records for required information. The data was then statistically processed. RESULTS: Thirty inpatient paediatric wards participated in the study (27 district wards and 3 university hospital wards), amounting to more than a third of all paediatric wards in the country. The total number of intoxications reported was 2,176, the majority of which were alcohol-related (84.5%), followed by cannabinoids and, to a lesser degree, amphetamines. The number of alcohol intoxications increased by 22% during the 5-year observation period, whilst the frequency of illegal drugs intoxications remained the same. We also observed an increase in the percentage of alcohol intoxications in girls - from 42% to 45.5%. The mean age at intoxication was low - 15.5 years. The Glasgow Coma Scale in individual episodes of intoxication increased during the study duration/follow up period. The proportion of alcohol intoxications originating in pubs, clubs or other public institutions was 25%. CONCLUSION: The number of alcohol intoxications has risen during the observation period. The age at which these intoxications occurred is very low. Of serious concern is the fact, that 25% of alcohol intoxications originated in places where alcohol is sold, despite the fact that majority of the adolescents were under the legal drinking age limit of 18 years.

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.

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.

Treatment of encapsulated pleural effusions in children: a prospective trial.

BACKGROUND: The aim of this study was to improve the efficacy of treatment of complicated pleural effusions. METHODS: In this prospective study, 76 consecutive children (average age 5.0 +/- 4.14 years) fulfilling the required classification criteria were duly treated with chest tube placement and divided into two groups depending on the presence of encapsulated or non-encapsulated effusions. Treatment of the former group was supplemented by intrapleural fibrinolysis. The effectiveness of treatment was assessed in terms of chest tube dwell-time and total length of hospitalization. Regression analysis was performed using independent factors that were associated with these dependent factors. Value differences for P < 0.05 were considered significant. RESULTS: The ultrasound pleural distance and lactic-dehydrogenase content in the pleural fluid was significantly associated with the length of treatment (P < 0.01). Improved response to treatment, reduced duration of hospitalization (9.2 +/- 1.9 vs 11.5 +/- 0.9; P < 0.01) and tube dwell-time (7.6 +/- 1.3 vs 9.5 +/- 0.9; P < 0.01) was achieved in the intrapleural-fibrinolysis-treated group (n= 38) compared with controls (n= 38), with virtually the same total tube output (606.1 +/- 257.5 vs 673.1 +/- 347.4; P= 0.175). All patients were completely cured. Following 104 applications of the fibrinolytic agent there was one change in coagulation parameters: hypofibrinogenemia (in 1%). CONCLUSIONS: The authors recommend intrapleural fibrinolysis as an effective and safe alternative treatment strategy in treating encapsulated pleural effusions in children.

Changes of serum thymidine kinase in children with acute leukemia.

BACKGROUND: Thymidine kinase (TK) is involved in nucleic acid synthesis and is therefore considered to be an important proliferation tumor marker. Our main goal was to determine the significance of elevated TK levels as a relapse marker during follow-up with child patients suffering from acute leukemia. PATIENTS AND METHODS: TK serum levels in 38 children with acute leukemia (34 lymphoblastic, 4 myeloblastic) were determined using radio-receptor analysis (RRA, Immunotech, Prague, USA). All patients included in this study had had TK examined before the start of the treatment and at least twice during the follow-up. RESULTS: Our results showed that TK serum levels at the time of diagnosis were extremely high (78-5826 U/l, median value 403 U/l, normal < 8 U/l), while in remission TK serum levels were much lower (5-80 U/l, median value 31 U/l). During relapse of acute leukemia (5 cases), TK levels increased considerably to measurements between 120-800 U/l (median value 324 U/l). The study showed that the elevation of TK serum levels during follow-up was a helpful marker for the recognition of an early stage of relapse and in some cases occurred as early as one month before the appearance of clinical signs. Sensitivity in this case was 87% and thus TK serum levels seem to be a very good parameter during follow-up because of acceptable sensitivity, low cost (4 $/sample) and the elimination of a requirement for screening of bone marrow samples. CONCLUSION: While TK serum levels were helpful in predicting relapse during follow-up, it is necessary to note that they did not correlate with prognosis in our group of patients during the time of the initial diagnosis of acute leukemia.

[Lethal course of rotavirus gastroenteritis - a case history.].

The case of fatal course of rotaviral gastroenteritis at eight months old boy has been described. Two days history of frequent watery stools in home care, hyperosmolar dehydration grading to hypovolemic shock, cardiopulmonary resuscitation in regional hospital, transported comatose with vital functions support. In spite of temporary stabilization of the patient, there was retrogression to multiorgan failure (ischemic myocardial infliction, circulatory failure, ARDS, renal failure, DIC, enteritis, post ischemic hepatopathy). Four day later patient exits. Rotaviruses have been proved from stools specimen post mortem.