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Introduction: Cardiopulmonary interactions influence cardiac output during mechanical ventilation. There is limited prospective data investigating these interactions in critically ill pediatric patients. Methods: We performed a prospective observational study to evaluate the influence of mechanical ventilation strategy on hemodynamic changes using ultrasound cardiac output monitoring (USCOM). This study was conducted with 56 children on protective mechanical ventilation for pulmonary (36 children) and non-pulmonary (20 children) pathology. Circulatory parameters (e.g., cardiac index and systemic vascular resistance index) were evaluated after initiation of mechanical ventilation and at 6, 12 and 48-hour intervals. The circulatory support therapy was indicated based on USCOM measurement results. Fluid balance was monitored. Results: No significant differences between the groups' hemodynamic profiles were found. Children ventilated for pulmonary pathology tended to require more frequent inotropic and combined inotropic/vasopressor circulatory support than did the children ventilated for non-pulmonary pathology. Children ventilated for non-pulmonary pathology tended to require more frequent vasopressor circulatory support after the initiation of mechanical ventilation. Both groups required a similar amount of fluid during the study. Conclusion: The protective strategy of mechanical ventilation was not associated with significant differences in hemodynamic profiles between patients with pulmonary and non-pulmonary pathologies. Although not statistically significant, a trend was observed toward a more frequent requirement for inotropic and combined inotropic/vasopressor therapy in children ventilated for pulmonary pathology, compared to those ventilated for non-pulmonary pathology. [ABSTRACT FROM AUTHOR]

Background: Severe lung diseases leading to respiratory failure are among the most frequent causes of critical conditions in childhood. Pulmonary injury leads to a systemic response of the organism and the response rate should be at the level of cytokines proportional to the degree of lung injury. The study aims to monitor systemic inflammatory response dependence on the degree of pulmonary injury using selected cytokines in pediatric patients. Methods: Thirty-two patients with severe pulmonary injury and Lung Injury Score >1.0 leading to respiratory failure were included. Mean age of enrolled patients was 39.5 months, weight 14.2 kg. Twenty-nine patients had primary lung disease ALI/ /ARDS based on aspiration, pulmonary infection, autoimmune process, pulmonary contusion, or pulmonary arterial hypertension, 3 patients secondary ARDS in septic shock and multiorgan failure. Patients were mechanically invasively ventilated. Patients were monitored during the study for 48 hours, laboratory sampling was performed in the 1st, 12th, 24th and 48th hour of experiment. Results: From observed markers matrix metalloproteinase MMP-9 was extremely high already in 1st hour with subsequent significant decrease. There was counter-regulatory increase of metalloproteinases inhibitor TIMP-1 at 12th hour related to initially high MMP-9. Expression of adhesion molecules was present already at the beginning of observation. ICAM-1 during the study descend insignificantly. VCAM-1 changes over time were statistically very significant with initial high levels and further decreasing the expression. Conclusions: On the set of critically ill children with severe pulmonary impairment were detected early systemic cytokine response with signs of endothelial activation. Changes in the spectrum of cytokines in severe lung disease may indicate the influence of other organ systems, not only on the level of blood gases exchange alterations resulting in tissue hypoxia. [ABSTRACT FROM AUTHOR]

Abstract 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.

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.2, 95% CI: 3.5-5.3, P < 10-6). BTNL8 encodes an intestinal epithelial regulator of Vγ4+γδ T cells implicated in regulating gut homeostasis. Enrichment was exclusive to MIS-C, being absent in patients with COVID-19 or bacterial disease. Using an available functional test for BTNL8, rare variants from a larger cohort of MIS-C patients (n = 835) were tested which identified eight variants in 18 patients (2.2%) with impaired engagement of Vγ4+γδ T cells. Most of these variants were in the B30.2 domain of BTNL8 implicated in sensing epithelial cell status. These findings were associated with altered intestinal permeability, suggesting a possible link between disrupted gut homeostasis and MIS-C-associated enteropathy triggered by SARS-CoV-2., (© 2024 Bellos et al.)

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., (© 2023. The Author(s).)

Objectives: Stroke volume (SV) and cardiac output monitoring is a cornerstone of hemodynamic assessment. Noninvasive technologies are increasingly used in children. This study compared SV measurements obtained by transcutaneous Doppler ultrasound techniques (ultrasonic cardiac output monitor [USCOM]), transthoracic echocardiography jugular (TTE-J), and parasternal (TTE-P) views performed by pediatric intensivists (OP-As) with limited training in cardiac sonography (20 previous examinations) and pediatric cardiologists (OP-Bs) with limited training in USCOM (30 previous examinations) in spontaneously ventilating children., Methods: A single-center study was conducted in 37 children. Each operator obtained 3 sets of USCOM SV measurements within a period of 3 to 5 minutes, followed with TTE measurements from both apical and jugular views. The investigators were blinded to each other's results to prevent visual and auditory bias., Results: Both USCOM and TTE methods were applicable in 89% of patients. The intraobserver variability of USCOM, TTE-J, and TTE-P were less than 10% in both investigators. The SV measurements by OP-As using USCOM, TTE-J, and TTE-P were 46.15 (25.48) mL, 39.45 (20.65) mL, and 33.42 (16.69) mL, respectively. The SV measurements by OP-Bs using USCOM, TTE-J, and TTE-P were 43.99 (25.24) mL, 38.91 (19.98) mL, and 37.58 (19.81) mL, respectively.The percentage error in SV with USCOM relative to TTE-J was 36% in OP-As and 37% in OP-Bs. The percentage error in SV with TTE-P was 33% relative to TTE-J in OP-As and 21% in OP-Bs., Conclusions: Our findings show that the methods are not interchangeable because SV values by USCOM are higher in comparison with the SV values obtained by TTE. Both methods have low level of intraobserver variability. The SV measurements obtained by TTE-P were significantly lower compared with the TTE-J for the operator with limited training in echocardiography. The TTE-P requires longer practice compared with the TTE-J; therefore, we recommend to prefer TTE-J to TTE-P for inexperienced operators., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

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.

Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disorder categorized into 3 phenotypic variants: infantile, juvenile, and adult. Four recent reports have linked NIID to CGG expansions in the NOTCH2NLC gene in adult NIID (aNIID) and several juvenile patients. Infantile NIID (iNIID) is an extremely rare neuropediatric condition. We present a 7-year-old male patient with severe progressive neurodegenerative disease that included cerebellar symptoms with cerebellar atrophy on brain MRI, psychomotor developmental regression, pseudobulbar syndrome, and polyneuropathy. The diagnosis of iNIID was established through a postmortem neuropathology work-up. We performed long-read sequencing of the critical NOTCH2NLC repeat motif and found no expansion in the patient. We also re-evaluated an antemortem skin biopsy that was collected when the patient was 2 years and 8 months old and did not identify the intranuclear inclusions. In our report, we highlight that the 2 methods (skin biopsy and CGG expansion testing in NOTCH2NLC) used to identify aNIID patients may provide negative results in iNIID patients., (© 2020 American Association of Neuropathologists, Inc. All rights reserved.)

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.

The primary objective was to create a clinically relevant model of right ventricular hypertension and to study right ventricular myocardial pathophysiology in growing organism. The secondary objective was to analyse the effect of oral enoximone (phosphodiesterase inhibitor) therapy on right ventricular haemodynamic parameters and myocardial changes in biomodel of right ventricular hypertension. The study included a total of 12 piglets of 42 days of age. Under general anaesthesia, pulmonary artery banding (PAB) was performed surgically to constrict the main pulmonary artery to about 70-80 % of its original dimension. The study presented two groups of animals labelled C (control animals with PAB; n = 8) and E (animals with PAB and oral administration of enoximone; n = 4). Direct pressure and echocardiographic measurements were taken during operation (time-1), and again at 40 days after surgery (time-2). The animals were killed, and tissue samples from the heart chambers were collected for quantitative morphological assessment. Statistical analysis was performed on all acquired data. At time-2, the median weight of animals doubled and the median systolic pressure gradient across the PAB increased (46.59 ± 15.87 mmHg vs. 20.29 ± 5.76 mmHg; p < 0.001). Changes in haemodynamic parameters were compatible with right ventricular diastolic dysfunction in all the animals. Apoptosis, tissue proliferation and fibrosis were identified in all the myocardial tissue samples. Right ventricular pressure overload leads to increased apoptosis of cardiac myocytes, proliferation and myocardial fibrosis. Our study did not show evidence of haemodynamic benefit or myocardial protective effect of oral enoximone treatment.

Objectives: To identify factors involved in reno-pulmonary interactions during mechanical ventilation., Materials and Methods: The study included a total of 25 domestic piglets. The animals were divided into three groups based on different strategies of ventilation. Group A; spontaneously breathing piglets; group B animals ventilated with tidal volume of 6 ml.kg-1 and group C with animals ventilated with tidal volume 10 ml.kg-1. Clinical monitoring and laboratory tests were performed for all groups at baseline and then at 1 hour and 12 hours for groups B and C. Ventilation indices, hemodynamics, urine output, creatinine clearance, glomerular filtration index, fractional excretion of sodium, free water clearance and tissue samples were recorded. The data obtained were statistically analysed., Results: Lower creatinine clearance and renal indices were seen in group B (p < 0.05) and in group C (p < 0.001) at 1 hour, and a difference in urine output for group C (p < 0.01) compared to group A was observed. At 12 hours, there was a further reduction in creatinine clearance and renal indices for group B (p < 0.05) and group C (p < 0.01). The lung mechanics and hemodynamics were not significantly influenced., Conclusions: The study showed a causal relationship between renal dysfunction and positive pressure mechanical ventilation with respect to tidal volume and time (Tab. 4, Fig. 2, Ref. 17).

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., (Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: The early identification of adverse interactions during mechanical ventilation, investigated by multiplexed immunoanalysis., Materials and Methods: Twenty piglets (average age 7 weeks, weight 23 kg) were intubated and divided into groups: A, spontaneously breathing; B, protectively ventilated; C, ventilated with injurious strategy; D, ventilated with lung disability. At the 1st hour (time-1) and 12th hour (time-2) of the study, brain natriuretic peptide (BNP), intercellular cell adhesion molecules (ICAM-1), vascular cell adhesion molecules (VCAM-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (Il-6) were analyzed in the blood., Results: The injurious ventilated group C exhibited an increase in both cell adhesion molecules (p<0.01), TNF-alpha and BNP (p<0.05) at time-1, and at time-2 further increases (p<0.05). In group D, an increase in ICAM-1 and BNP (p<0.05) at time-1, and increases in Il-6 and ICAM-1 (p<0.05) at time-2, with notable decreases in urine output were observed. Overall, the lung damage correlated with TNF-alpha (r=0.904), Il-6 (r=0.740), and ICAM-1 (r=0.756) levels., Conclusion: All five monitored molecules quickly and reliably signaled adverse interactions.

Objective: Evidence-based medicine currently dictates that in children, the controlled hypothermia may be applied only to the first degree and only in cases of neonatal encephalopathy and acute brain injury. Current recommendations are limited in terms of indication as well as by their very low degree of relevance (47.1%)., Data Source: The conclusions of published clinical and experimental studies, and ultimately the ongoing study of our clinical work. In our study, we monitored the core body temperature, brain bioelectrical potentials and infarction, heart rate, systemic venous and arterial pressure, cardiac output, hourly diuresis, and haemostasis parameters., Study Selection: Distinct designs of clinical and experimental studies make it difficult to compare their outputs., Data Synthesis: The aim of this article is to expand our current knowledge of resuscitation care in children as well as that of the use of therapeutic hypothermia. The introduction of this method into routine pediatric clinical practice is hindered by lack of an explicitly defined therapeutic protocol., Conclusion: The method of therapeutic hypothermia is not a predictor of survival but its proper implementation can be the key to the recovery of functions of body organs and systems after successful cardiopulmonary resuscitation. Unfortunately, this method is associated with adverse effects, namely with myocardial depression during the induction phase, and life-threatening complications after bringing the core of body to normal temperature. To increase the patient safety we have developed a safe strategy. Our protocol provides a relatively rapid induction, short interval of active cooling and passive rewarming over a long period of time (Tab. 3, Fig. 1, Ref. 34). Full Text in free PDF www.bmj.sk.

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.

Introduction: The "open lung concept" theory of mechanical ventilation is correct, but an unsuitable setting of the machine is not appropriate in children., Type of Study: This experimental study is a comparative, closed, randomized, double-blind study. The aim of the study was to verify the hypothesis that even a short-term high tidal volume during the course of mechanical ventilation damages the lung parenchyma as well as extra-pulmonary organs., Material and Methods: The inappropriate strategy of mechanical lung ventilation was simulated on an animal model. The study was performed on 30 healthy white domestic piglets (25 kg). Using a random selection, the piglets with healthy lungs were ventilated for 120 minutes under general anaesthesia with two different strategies of mechanical ventilation, i.e. 15 animals achieving alveolar hyperinflation with a high tidal volume (14 ml.kg(-1)), and 15 animals according to the "lung protective strategy" principle. Lung tissue samples were examined morphologically using the blind test method, and the proinflammatory cytokines levels were assessed in the piglets' serum., Results: The study demonstrated that a high tidal volume during mechanical lung ventilation with permanent positive pressure after 120 minutes induced very important morphological and functional lung changes that unfavourably influenced blood circulation, reduced cardiac output and induced a systemic inflammatory reaction (Fig. 9, Ref. 11).