Reviewing the use of zebrafish for the detection of neurotoxicity induced by chemical mixtures through the analysis of behaviour.

The knowledge and assessment of mixtures of chemical pollutants in the aquatic environment is a complex issue that is often challenging to address. In this review, we focused on the use of zebrafish (Danio rerio), a vertebrate widely used in biomedical research, as a model for detecting the effects of chemical mixtures with a focus on behaviour. Our aim was to summarize the current status of the ecotoxicological research in this sector. Specifically, we limited our research to the period between January 2012 and September 2023, including only those works aimed at detecting neurotoxicity through behavioural endpoints, utilizing zebrafish at one or more developmental stages, from egg to adult. Additionally, we gathered the findings for every group of chemicals involved and summarised data from all the works we included. At the end of the screening process 101 papers were considered eligible for inclusion. Results show a growing interest in zebrafish at all life stages for this kind of research in the last decade. Also, a wide variety of different assays, involving different senses, was used in the works we surveyed, with exposures ranging from acute to chronic. In conclusion, the results of this study show the versatility of zebrafish as a model for the detection of mixture toxicity although, for what concerns behavioural analysis, the lack of standardisation of methods and endpoints might still be limiting.

Cardiopulmonary Exercise Testing after Surgical Repair of Tetralogy of Fallot-Does Modality Matter?

BACKGROUND: Despite a successful repair of tetralogy of Fallot (rToF) in childhood, residual lesions are common and can contribute to impaired exercise capacity. Although both cycle ergometer and treadmill protocols are often used interchangeably these approaches have not been directly compared. In this study we examined cardiopulmonary exercise test (CPET) measurements in rToF. METHODS: Inclusion criteria were clinically stable rToF patients able to perform a cardiac magnetic resonance imaging (CMR) and two CPET studies, one on the treadmill (incremental Bruce protocol) and one on the cycle ergometer (ramped protocol), within 12 months. Demographic, surgical and clinical data; functional class; QRS duration; CMR measures; CPET data and international physical activity questionnaire (IPAQ) scores of patients were collected. RESULTS: Fifty-seven patients were enrolled (53% male, 20.5 ± 7.8 years at CPET). CMR measurements included a right ventricle (RV) end-diastolic volume index of 119 ± 22 mL/m2, a RV ejection fraction (EF) of 55 ± 6% and a left ventricular (LV) EF of 56 ± 5%. Peak oxygen consumption (VO2)/Kg (25.5 ± 5.5 vs. 31.7 ± 6.9; p < 0.0001), VO2 at anaerobic threshold (AT) (15.3 ± 3.9 vs. 22.0 ± 4.5; p < 0.0001), peak O2 pulse (10.6 ± 3.0 vs. 12.1± 3.4; p = 0.0061) and oxygen uptake efficiency slope (OUES) (1932.2 ± 623.6 vs. 2292.0 ± 639.4; p < 0.001) were significantly lower on the cycle ergometer compared with the treadmill, differently from ventilatory efficiency (VE/VCO2) max which was significantly higher on the cycle ergometer (32.2 ± 4.5 vs. 30.4 ± 5.4; p < 0.001). Only the VE/VCO2 slope at the respiratory compensation point (RCP) was similar between the two methodologies (p = 0.150). CONCLUSIONS: The majority of CPET measurements differed according to the modality of testing, with the exception being the VE/VCO2 slope at RCP. Our data suggest that CPET parameters should be interpreted according to test type; however, these findings should be validated in larger populations and in a variety of institutions.

Recurrent thoracic air leak syndrome in patients affected by pulmonary graft-versus-host disease: Surgical strategies and outcome.

BACKGROUND AND AIMS: Thoracic air leak syndrome (TALS) is a complication related to chronic pulmonary graft-versus-host disease (pGvHD) that affects approximately 0.83%-3.08% patients after allogenic hematopoietic stem cell transplant. Such complication is defined as the occurrence of any form of air leak in the thorax, including spontaneous pneumomediastinum or pneumopericardium, subcutaneous emphysema, interstitial emphysema and pneumothorax and has a negative impact on post-transplant survival. The aim of the present study is to describe a single-center experience in the surgical management of recurrent TALS in adolescents and young adults and its outcome. METHODS: We retrospectively reviewed the clinical notes of patients with previous allogenic hematopoietic stem cell transplant who underwent surgical procedures for recurrent TALS from January 2016 until March 2021. We analyzed clinical data, number of episodes of thoracic air leak, surgical procedures and relative outcome. RESULTS: In the examined period, four patients, aged 16-25 years, underwent surgical procedures for TALS, including thoracostomy tube placement, thoracoscopic pleurodesis and thoracotomy. All the patients had been diagnosed with pGvHD before the onset of TALS, with a mean time lapse of 276 days (range 42-513). These patients experienced on average 4.5 air leak episodes (range 3-6). All the patients experienced at least two episodes before surgery. One patient underwent emergency tube thoracostomy only, three patients underwent thoracoscopic pleurodesis and two patients underwent thoracotomy. After surgery, patients were free from air leak symptoms for a mean time of 176 days (range 25-477). Pulmonary function progressively deteriorated, and all the patients eventually died because of respiratory failure after a mean time of 483 days (range 127-1045) after the first episode of air leak. CONCLUSIONS: Surgery provides temporary relief to symptoms related to TALS but has limited effects on the underlying pathophysiologic process. The development of TALS in a sign of progressive pulmonary function worsening and is associated with high risk of respiratory failure and mortality.

Differences in Physical Activity Levels between Healthy and Transplanted Children: Who Needs More Tips?

BACKGROUND: Advances in the medical-surgical field have significantly increased the life expectancy of patients undergoing solid organ transplantation but this exposes patients to long-term complications due to chronic therapies and changes in lifestyle. It is known that children affected by pathology tend to be more sedentary and inactivity represents a further risk factor for the onset of non-communicable diseases. The aim of the present study was to compare the lifestyle of two groups of young patients: one group of healthy subjects (HG) and one group of kidney or liver transplant recipients (TG). METHODS: Patients were asked to complete Physical Activity Questionnaire for Older Children (PAQ-C). RESULTS: A total of 104 subjects were recruited (50.9% male, mean age 12.8 ± 3.16 years old). No significant differences were observed in the final score between groups when comparing subjects based on health condition (Healthy 2.69 ± 0.65 vs. Transplant Group 2.42 ± 0.88), the intensity of sports activities (Competitive 2.82 ± 0.59 vs. Not Competitive 2.53 ± 0.7) or type of transplant (Liver 2.51 ± 0.91 vs. Kidney 2.16 ± 0.75). CONCLUSION: The results of this study showed a worrying reality: children are engaged in low levels of physical activity regardless of their health status and in general the level of activity does not reach the recommended values even in the absence of contraindications. So, it is necessary to encourage healthy children to practice more PA and to introduce PA prescriptions for transplanted children to prevent their health from deteriorating due to sedentariness.

Cardiopulmonary Exercise Testing in Children and Young Adolescents after a Multisystem Inflammatory Syndrome: Physical Deconditioning or Residual Pathology?

Multisystem inflammatory syndrome in children (MIS-C) is a serious health condition that imposes a long-term follow-up. The purpose of our pilot study is to evaluate the usefulness of the cardiopulmonary stress test (CPET) in the follow-up after MIS-C. All patients admitted for MIS-C in our hospital in the 12 months preceding the date of observation were considered for inclusion in the study. Pre-existing cardio-respiratory diseases and/or the lack of collaboration were the exclusion criteria. At enrolment, each subject passed a cardiological examination, rest ECG, echocardiogram, 24 h Holter-ECG, blood tests, and a CPET complete of spirometry. A total of 20 patients met the inclusion criteria (11.76 ± 3.29 years, 13 male). In contrast to the normality of all second-level investigations, CPET showed lower-than-expected peakVO2 and peak-oxygen-pulse values (50% of cases) and higher-than-expected VE/VCO2-slope values (95% of cases). A statistically significant inverse correlation was observed between P-reactive-protein values at admission and peakVO2/kg values (p = 0.034), uric acid values at admission, and peakVO2 (p = 0.011) or peak-oxygen-pulse expressed as a percentage of predicted (p = 0.021), NT-proBNP values at admission and peakVO2 expressed as a percentage of predicted (p = 0.046). After MIS-C (4-12 months) relevant anomalies can be observed at CPET, which can be a valuable tool in the follow-up after this condition.

Higher Troponin Levels on Admission are associated With Persistent Cardiac Magnetic Resonance Lesions in Children Developing Myocarditis After mRNA-Based COVID-19 Vaccination.

BACKGROUND: Acute pericarditis/myocarditis is a rare complication of the mRNA-based vaccines and although mostly self-limiting, long-term sequelae remain unclear. METHODS: We enrolled all patients admitted to the emergency department between September 2021 and February 2022 meeting the CDC work case definition, with symptoms onset after mRNA-based COVID-19 vaccine. Alternative virologic causes were excluded. Clinical data, laboratory values, cardiologic evaluation, electrocardiogram (ECG), and echocardiogram (ECHO) were collected on admission, at discharge, and during follow-up in all patients. Cardiac Magnetic Resonance (CMR) was performed only in those with signs consistent with myocarditis. RESULTS: We observed 13 patients (11M and 2F), median age 15 years, affected by acute pericarditis/myocarditis after COVID-19 mRNA vaccination (11 after Comirnaty® and 2 after Spikevax®). Symptoms'onset occurred at a median of 5 days (range, 1 to 41 days) after receiving mRNA vaccine (13 Prizer 2 Moderna): 4 patients (31%) after the 1st dose, 6 (46%) after the 2nd, and 3 (23%) after 3rd dose. Increased levels of high-sensitive troponin T (hsTnT) (median 519,5 ng/mL) and N-terminal-pro hormone BNP (NT-proBNP) (median 268 pg/mL) and pathognomonic ECG and ECHO abnormalities were detected. On admission, 7 of 13 (54%) presented with myopericarditis, 3 (23%) with myocarditis, and 3 (23%) with pericarditis; CMR was performed in 5 patients upon pediatric cardiologist prescription and findings were consistent with myocarditis. At 12 weeks of follow-up, all but one patient (92%), still presenting mild pericardial effusion at ECHO, were asymptomatic with normal hsTnT and NT-proBNP levels and ECG. On CMR 6 of 9 patients showed persistent, although decreased, myocardial injury. Higher hsTnT levels on admission significantly correlated with persistent CMR lesions. CONCLUSION: Evidence of persistent CMR lesions highlights the need for a close and standardized follow-up for those patients who present high hsTnT levels on admission.

Preliminary Evaluation of Sedentary Lifestyle in Italian Children after Solid Transplant: What Role Could Physical Activity Play in Health? It Is Time to Move.

BACKGROUND: Advances in the medical-surgical field have significantly increased survival after solid organ transplantation in the pediatric population. However, these patients are predisposed to the development of long-term complications (e.g., cardiovascular disease). The therapeutic role of physical activity (PA) to counteract these complications is well known. The purpose of the study was to investigate the level of PA in a pediatric population after solid organ transplantation. METHODS: In the first 4 weeks at the beginning of the school year, the Physical Activity Questionnaire for Older Children and Adolescents was administered to young patients who had previously undergone solid transplants at our institute. RESULTS: Questionnaires of 49 patients (57.1% female, mean age 13.2 ± 3.5 years) were analyzed and 32.7% of subjects did not perform any exercise during school physical education classes. Only 24% practiced a moderate quantity of exercise in the previous week (2-3 times/week) and 72% engaged in sedentary behaviors during weekends. CONCLUSIONS: Preliminary data confirmed that young recipients are still far from meeting the minimum indications of the World Health Organization on PA and sedentary behavior. It will be necessary to increase their involvement in PA programs in order not only to increase their life expectancy but also to improve their quality of life.

Re-evaluation After 2 Years of COVID-19 Pandemic: Return to Play in Pediatric Population: What's New?

An observational retrospective study was conducted on 180 young competitive athletes. These children were revaluated after a mild/moderate SARS-CoV-2 infection through 3 different kind of protocol aimed at recognizing any cardiorespiratory complications due to the infection. The aim of the present study was to evaluate the results of "return to play" Italian protocols for readmission to competitive sport in the pediatric population. All of the subjects analyzed were readmitted to competitive sports after revaluation. None of the young athletes showed cardiorespiratory compromises at first and/or second level evaluation, confirming that in young population there is low risk of hospitalization and life-threatening complications after a mild/moderate infection. Italian simplified protocol for resuming sport have proved to be a valuable tool for health assessment both in adult and young athletes allowing them to resume their training in safety.

Late outcome of extracardiac Fontan patients: 32 years of follow-up.

OBJECTIVES: We sought to evaluate the long-term survival and risk factors for morbidity and mortality in our cohort of patients after extracardiac (EC) Fontan. METHODS: We collected and analysed follow-up data until September 2020 for all patients who underwent EC Fontan operation at our institution from November 1988 to November 2015. RESULTS: Out of 406 patients treated with EC Fontan at a mean age of 5.4 ± 4.5 years, 372 (91.6%) were discharged home; 15% were lost to follow-up. The median follow-up was 14.6 years (interquartile range 8.7-20.3). Two hundred patients (54%) had a good long-term outcome, with an event-free long-term survival, but late adverse events of any kind needing interventional or surgical reoperations were reported in 128 patients (34%). Forty-four patients (12%) developed late Fontan failure. Thirty-seven survivors (10%) had late arrhythmias, with the need for pacemaker implantation. Obstruction of the cavopulmonary pathway occurred in 49 patients (13%), but just 8 patients needed conduit surgical replacement. At 32 years, the survival probability was 84%. The risk of orthotopic heart transplant, considering death as a competing event (showed as cumulative incidence), was 12.5%. A preoperative diagnosis of hypoplastic left heart syndrome was an independent risk factor for the need for heart transplant. CONCLUSIONS: The EC Fontan shows satisfactory long-term survival and low incidence of adverse events and late failure. Conduit replacement is rare, and its longevity may not represent a substantial issue in these patients. However, as with other technical variants, the need for reoperations during long-term follow-up is a significant challenge.

Competitive sport after SARS-CoV-2 infection in children.

BACKGROUND: With the gradual resumption of sports activities after the lock-down period for coronavirus pandemic, a new problem is emerging: Allow all athletes to be able to return to compete after SARS-CoV-2 infection in total safety. Several protocols have been proposed for healed athletes but all of them have been formulated for the adult population. The aim of the present study is to evaluate the adequacy of Italian practical recommendations for return-to-paly, in order to exclude cardiorespiratory complications due to COVID-19 in children and adolescents. METHODS: Between April 2020 and January 2021 the Italian Sports Medical Federation formulated cardiorespiratory protocols to be applied to athletes recovered from SARS-CoV-2 infection. The protocols take into account the severity of the infection. Protocols include lung function tests, cardiopulmonary exercise test, echocardiographic evaluation, blood chemistry tests. RESULTS: From September 2020 to February 2021, 45 children and adolescents (aged from 9 to 18 years; male = 26) with previous SARS-CoV-2 infection were evaluated according to the protocols in force for adult. 55.5% of the subjects (N = 25) reported an asymptomatic infection; 44.5% reported a mild symptomatic infection. Results of lung function test have exceeded the limit of 80% of the theoretical value in all patients. The cardiorespiratory capacity of all patients was within normal limits (average value of maximal oxigen uptake 41 ml/kg/min). No arrhythmic events or reduction in the ejection fraction were highlighted. CONCLUSION: The data obtained showed that, in the pediatric population, mild coronavirus infection does not cause cardiorespiratory complications in the short and medium term. Return to play after Coronavirus infection seems to be safe but it will be necessary to continue with the data analysis in order to modulate and optimize the protocols especially in the pediatric field.

The Effects of Physical Inactivity and Exercise at Home in Young Patients with Congenital Heart Disease during the COVID-19 Pandemic.

Background: The COVID-19 pandemic had a significant impact on the population's ability to be physically active. Purpose: Evaluate the effect of the COVID-19 mitigation measures on exercise tolerance in patients with congenital heart disease (CHD). Materials and methods: All subjects (880, 6-18 years old) who performed a stress test at our hospital from October 2020 to February 2021 and had a similar test one year earlier were enrolled. A questionnaire on the degree of physical activity carried out in 2020 concerning the period prior to the pandemic was compiled. Exercise tolerance and the main anthropometric parameters between the first and second tests were compared. Results: 110 subjects (11.9 ± 4.1 years) were included in the study. The percentage of patients engaged in regular physical activity (RPA) decreased significantly during the pandemic (p < 0.001), and BMI increased significantly (p < 0.001), except among the subjects who began RPA during the lockdown, whereas test duration did not decrease significantly overall but increased in this last subgroup (p < 0.05) Conclusions: The COVID-19 lockdown led to a less active lifestyle with a significant increase in BMI in our group of CHD. These data could have negative effects on the risk profile of this population. RPA practiced at home seems to be effective in counteracting such effects.

[Physical activity in patients with repaired and unrepaired congenital heart diseases. Task Force for exercise prescription in patients with congenital heart disease of the Italian Society of Pediatric Cardiology and Congenital Heart Disease]. / L'attività fisica nei soggetti con cardiopatia congenita in storia naturale ed operata. Task Force sull'attività fisica nel cardiopatico congenito della Società Italiana di Cardiologia Pediatrica e delle Cardiopatie Congenite.

Regular physical activity is essential for physical health and mental wellbeing in children and teenagers. However, patients with congenital heart disease are often restricted from being physically active due to parental overprotection and lack of physical activity promotion or exercise prescription from their physicians. A comprehensive medical evaluation is crucial for the development of personalized exercise programs for these patients. The aim of this review is to provide physicians with a practical guide on how to promote physical activity and prescribe exercise for patients with congenital heart disease with or without surgical correction.

Impact of complex congenital heart disease on the prevalence of arterial hypertension after aortic coarctation repair.

OBJECTIVES: This study was designed to evaluate the difference in the prevalence of long-term arterial hypertension among patients with corrected aortic coarctation according to the existence of associated cardiac congenital lesions. METHODS: We identified 235 patients who had undergone surgery for aortic coarctation and classified them into 2 groups: patients with isolated coarctation of the aorta (CoA) and patients with aortic coarctation associated with complex congenital heart disease. Data were retrospectively analysed. RESULTS: There were 148 subjects with isolated CoA and 87 with complex CoA (CoA-c). Patients were defined as hypertensive if they required antihypertensive treatment and/or when blood pressure was above 95th percentile. Patients with isolated aortic coarctation were significantly younger than patients with CoA-c (P < 0.001) and a markedly higher prevalence of arterial hypertension (44% vs 24%) was documented in the isolated coarctation group. The difference in the prevalence of hypertension in the 2 groups was still significant after correcting for differences in age (P < 0.001), confirming that the prevalence of arterial hypertension in patients with CoA-c was half of that of patients with isolated CoA. CONCLUSIONS: We conclude that complex congenital heart disease in patients who have undergone surgical correction for aortic coarctation results in a significantly lower prevalence of late-onset hypertension. Reduced systemic flow and pressure before surgery in patients with CoA-c might be associated with a lower rate of arterial hypertension.

Association between nocturnal blood pressure dipping and insulin resistance in children affected by NAFLD.

UNLABELLED: The aim of this study was to analyse the relationship between insulin-glucose metabolism, nocturnal blood pressure dipping and nonalcoholic fatty liver disease (NAFLD) in obese adolescents without diabetes. One hundred one consecutive children, with biopsy-proven NAFLD, were included in this study. Blood samples were drawn for the analyses of liver function tests, insulin-glucose metabolism and lipid profile appraisal. An ambulatory blood pressure measurement (ABPM) was performed. Seventy-six children (75.3 %) were systolic nondippers, and 23 of them were diastolic nondippers (30.3 %). No differences were found in the anthropometric parameters between the two groups. When compared to the systolic dippers, the systolic nondippers had higher medians of mean nocturnal blood pressure, glucose at 0, 60 and 120 min in the oral glucose tolerance test (OGTT), OGTT insulin at all time points and insulin-resistance values. No correlation of histopathological features with dipping/nondipping statuses was found. CONCLUSIONS: We found an association between a nocturnal blood pressure fall and measures of insulin levels, independent of obesity, or daytime blood pressure levels, among the obese patients with NAFLD. Although no association between nondipping profiles and NAFLD was observed in our study, further studies with a longer term follow-up are needed, to better elucidate the complex link between these particular entities.

Physical activity, fitness, and dyspnea perception in children with congenital diaphragmatic hernia.

We assessed whether physical activity could influence the performance and perception of dyspnea in children who were operated on for high risk congenital diaphragmatic hernia (CDH). We hypothesized that CDH children with normal activity would have better lung function and exercise performance level when compared to sedentary CDH subjects. We studied 18 children (11 males and 7 females, mean age 6.6 ± 2.6 years) who were surgically corrected. All children underwent physical examination, ECG at rest, and a maximal exercise stress test on a treadmill to measure the duration of exercise, maximal heart rate and blood pressure, maximal oxygen uptake (VO(2) max and VO(2) ml/kg/min). Lung function testing to measure forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV(1) ), and peak expiratory flow (PEF) was also performed. Following the stress test, the Dalhousie dyspnea and effort scale was shown to children as a pictorial panel with three groups of increasing (from 1 to 7) levels of effort perception, throat discomfort, and chest dyspnea. Children were divided into group A (sedentary) and group B (regular physical participation). There was no difference in CDH severity between the two groups. Group A had a statistically significant lower duration of exercise (P < 0.01), maximal oxygen consumption (VO(2) max P < 0.0001), VO(2) ml/kg/min (P < 0.001), higher throat closing feeling (P < 0.004), chest dyspnea (P < 0.001), and effort perception (P < 0.04) compared to group B. No differences were found in lung function tests. In conclusion, our data may suggest that children with a history of CDH who are active maintain a higher level of performance with less perception of dyspnea and effort.