Non-VKA Oral Anticoagulants in Adult Congenital Heart Disease: a Single-Center Study.

PURPOSE: Non-VKA oral anticoagulants (NOACs) prescription is increasing in adults with congenital heart disease (ACHD). However, data on efficacy and safety in ACHD is unclear, particularly in severe CHD. The study aimed to review the safety and efficacy of NOACs in ACHD. METHODS: Retrospective evaluation of ACHD patients started on NOACs from 2014 to 2020, with the primary endpoints of bleeding or thromboembolic events (TE). CHA2DS2-VASc and HAS-BLED scores were calculated, mortality was assessed, and risk factors for bleeding were identified. RESULTS: A total of 93 patients were included, the mean age was 52 ± 15 years, 58% were female, 55.9% had moderate CHD, and 23.7% had severe CHD (3.2% Fontan). Most (66%) had a CHA2DS2-VASc score ≥ 2 and 82% HAS-BLED ≤ 2. In a median follow-up of 41 (IQR 21) months (400.4 patient-years), there were TE in two patients. The annual risk for TE was 0.49%/patient/year. The cardiovascular mortality was 2% and all-cause mortality 5%; there were no fatal TE or bleeding events. Minor (n = 6, 6.5%) and major (n = 3, 3.2%) bleeding events were observed, a median of 12 (IQR 15) months after starting NOAC therapy. The annual risk for bleeding was 2.2%/patient/year. Renal disease (HR 14.6 [95% CI 1.23-73.6], p = 0.033) and the HAS-BLED score were predictors of major (adjusted HR 6.97 [95% CI 1.69-28.78], p = 0.007) and minor (adjusted HR 3.80 [95% CI 1.48-9.78], p = 0.006) bleeding complications. CONCLUSION: In this real-life cohort of selected ACHD, the use of NOACs was safe and effective, with a low incidence of bleeding events.

Infective endocarditis in a cohort of adult CHD patients.

BACKGROUND: CHD increases the risk of infective endocarditis due to the substrate of prosthetic materials and residual lesions. However, lesion-specific and mortality risks data are lacking. We sought to analyse clinical course and mortality of infective endocarditis in a cohort of adult CHD. METHODS: Retrospective analysis of all cases of proven and probable infective endocarditis (Duke's criteria) followed in our adult CHD clinic between 1970 and August, 2021. Epidemiological, clinical and imaging data were analysed. Predictors of surgical treatment and mortality were assessed using regression analysis. RESULTS: During a mean follow-up of 15.8 ± 10.9 years, 96 patients had 105 infective endocarditis episodes, half with previous cardiac surgery (corrective or palliative). The most frequent diagnoses were: ventricular septal defect, bicuspid aortic valve, Tetralogy of Fallot and pulmonary atresia. The site of infection was identified by echocardiography in 82 episodes (91%), most frequently in aortic (n = 27), tricuspid (n = 15), and mitral (n = 13) valves. Blood cultures were positive in 79% of cases, being streptococci (n = 29) and staphylococci (n = 23) the predominant pathogens. Surgery was necessary in 40% and the in-hospital mortality was 10.5%, associated with heart failure (p < 0.001; OR 13.5) and a non-surgical approach (p = 0.003; OR 5.06). CONCLUSIONS: In an adult CHD cohort, infective endocarditis was more frequent in patients with ventricular septal defect and bicuspid aortic valves, which contradicts the current guidelines that excludes them from prophylaxis. Surgical treatment is often required and mortality remains substantial. Prevention of this serious complication should be one of the major tasks in the care of adults with CHD.

Dermal Delivery of Lipid Nanoparticles: Effects on Skin and Assessment of Absorption and Safety.

During the recent decades, dermal delivery has achieved visible popularity mainly due to the increase of chronic skin diseases and the demand for targeted delivery and patient compliance. Dermal delivery provides an attractive alternative to oral drug delivery, promoting the drug application directly at the site of action, resulting in higher localized drug concentration with reduced systemic drug exposure. Among several types of drug delivery systems used in dermal delivery are the lipid nanoparticles, which include solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). These lipid nanocarriers have attracted great interest and have been intensively studied for their use in dermal applications. Lipid nanoparticles increase the transport of active compounds through the skin by improving drug solubilization in the formulation, drug partitioning into the skin, and fluidizing skin lipids. Moreover, these nanocarriers are composed of biologically active and biodegradable lipids that show less toxicity and offer many favorable attributes such as adhesiveness, occlusion, skin hydration, lubrication, smoothness, skin penetration enhancement, modified release, improvement of formulation appearance providing a whitening effect, and offering protection of actives against degradation.This chapter focuses on the effects of lipid nanoparticles in dermal delivery, on the types of active compounds that are used in their formulation and application, some aspects related to their possible toxicity, and a description of the most commonly used techniques for the evaluation of drug absorption on the skin.

LipNanoCar Technology - A Versatile and Scalable Technology for the Production of Lipid Nanoparticles.

The extensive knowledge in the miniemulsion technique used in biocatalysis applications by the authors allowed the development of drug delivery systems that constitutes the LipNanoCar technology core for the production of lipid nanoemulsions and solid lipid nanoparticles. The LipNanoCar technology, together with adequate formulations of different oils, fatty acids, surfactants, and temperature, allows the entrapment of several bioactive and therapeutic compounds in lipid nanoparticles for cosmetic, nutrition, and pharmaceutical applications.The LIpNanoCar technology allowed lipid nanoparticles production with average sizes ranging from 100 to 300 nm and Zeta Potentials between -55 and -20 mV. Concomitantly, high entrapment or encapsulation efficiencies (%EE) were achieved, as illustrated in this work for ß-carotene and vitamins derivatives (>85%) for cosmetic application, and for antibiotics currently used in chemotherapy, like rifampicin (69-85%) and pyrazinamide (14-29%) against Mycobacterium tuberculosis (TB), and ciprofloxacin (>65%) and tobramycin (~100%) in Cystic Fibrosis (CF) respiratory infections therapy. Ciprofloxacin presented, for example, a quick-release from the lipid nanoparticles using a dialysis tubing (96% in the first 7 h), but slower than the free antibiotic (95% in the first 3 h). This result suggests that ciprofloxacin is loaded near the external surface of the lipid nanoparticles.The toxicity and validation of entrapment of antibiotics in lipid nanoparticles for Cystic Fibrosis therapy were assessed using Caenorhabditis elegans as an animal model of bacterial infection. Fluorescence microscopy of an entrapped fluorescent dye (DiOC) confirmed the uptake of the lipid nanoparticles by ingestion, and their efficacy was successfully tested in C. elegans. Burkholderia contaminans IST408 and Burkholderia cenocepacia K56-2 infections were tested as model bacterial pathogens difficult to eradicate in Cystic Fibrosis respiratory diseases.

Campylobacter coli Myocarditis: a case report.

We report the case of a 14-year-old male presented with raised myocardial injury biomarkers, on the workout, Campylobacter coli was identified on stool culture, treated with antibiotics with total resolution. Cardiac magnetic resonance showed interventricular septum and lateral wall hypokinesia and subepicardial delayed enhancement, with preserved ventricular systolic function. To our knowledge, this is the first report linking Campylobacter coli to myopericarditis in children.

Paediatric giant cell myocarditis: a case report.

A previously healthy 15-year-old teenage boy was admitted for fever and heart failure. Myocarditis was suspected, and endomyocardial biopsy revealed giant cell myocarditis. Immunosuppressive treatment was initiated, with excellent response. A plausible link to previous leptospirosis was identified. At 18-month follow-up, left ventricular function is normal. Only one other reported case of paediatric giant cell myocarditis had such a favourable outcome.

Prognostic power of anaerobic threshold parameters in patients with transposition of the great arteries and systemic right ventricle.

INTRODUCTION: Both transposition of the great arteries (TGA) previously submitted to a Senning/Mustard procedure and congenitally corrected TGA (cc-TGA) have the systemic circulation supported by the morphological right ventricle, thereby rendering these patients to heart failure events risk. The aim of this study was to evaluate cardiopulmonary exercise test parameters for stratifying the risk of heart failure events in TGA patients. METHODS: Retrospective evaluation of adult TGA patients with systemic circulation supported by the morphological right ventricle submitted to cardiopulmonary exercise test in a tertiary centre. Patients were followed up for at least 1 year for the primary endpoint of cardiac death or heart failure hospitalisation. Several cardiopulmonary exercise test parameters were analysed as potential predictors of the combined endpoint and their predictive power were compared (area under the curve). RESULTS: Cardiopulmonary exercise test was performed in 44 TGA patients (8 cc-TGA), with a mean age of 35.1 ± 8.4 years. The primary endpoint was reached by 10 (22.7%) patients, with a mean follow-up of 36.7 ± 26.8 months. Heart rate at anaerobic threshold had the highest area under the curve value (0.864), followed by peak oxygen consumption (pVO2) (0.838). Heart rate at anaerobic threshold ≤95 bpm and pVO2 ≤20 ml/kg/min had a sensitivity of 87.5 and 80.0% and a specificity of 82.4 and 76.5%, respectively, for the primary outcome. CONCLUSION: Heart rate at anaerobic threshold ≤95 bpm had the highest predictive power of all cardiopulmonary exercise test parameters analysed for heart failure events in TGA patients with systemic circulation supported by the morphological right ventricle.

RoPE Score as a Predictor of Recurrent Ischemic Events After Percutaneous Patent Foramen Ovale Closure.

The benefits of patent foramen ovale (PFO) closure for cryptogenic stroke secondary prevention are still debated. The Risk of Paradoxical Embolism (RoPE) study developed a score to improve patient selection for this procedure. We proposed to assess the validity of this score to assess the prognostic impact of PFO closure.From 2000 to 2014, all consecutive patients submitted to PFO closure were included in a prospective registry in a university center. The primary endpoint was recurrent ischemic cerebrovascular events and the secondary endpoints were all-cause, neurological, and cardiac mortality rates and new-onset atrial fibrillation (NOAF) rates. In total, 403 patients were included in the study (women: 52.1%; mean age: 44.7 ± 10.9 years). The mean follow-up period was 6.4 ± 3.7 years. Immediate success was achieved in 97% patients. There were 23 (5.8%) ischemic cerebrovascular events, 8 (2.0%) deaths, and 17 (4.3%) NOAFs. The mean RoPE score was 6.10 ± 1.79. Smoker status, coronary artery disease, lower RoPE score, and higher left atrial dimensions were predictors of the primary endpoint. However, a lower RoPE score and coronary artery disease remained independent predictors in multivariate analysis.RoPE score was shown to be an independent predictor of recurrent ischemic cerebrovascular events, and a score of ≤ 6 was shown to identify patients with significantly higher risk of mortality and recurrent ischemic events.

Long-term results of percutaneous balloon valvuloplasty in neonatal critical pulmonary valve stenosis: a 20-year, single-centre experience.

Introduction Percutaneous balloon valvuloplasty is the primary treatment for critical pulmonary valve stenosis in neonates. Thus far, a few studies have reported long-term results of this technique in neonatal critical pulmonary valve stenosis. METHODS: We carried out a retrospective study of all consecutive newborns with critical pulmonary valve stenosis subjected to percutaneous balloon valvuloplasty at a single centre, between 1994 and 2014, to assess its immediate and long-term safety and efficacy. RESULTS: A total of 24 neonates presented with critical pulmonary valve stenosis. The mean diameter of the pulmonary annulus was 7 mm (±1.19); 33.3% had a dysplastic pulmonary valve, and 92% were started on prostaglandin E1 treatment. Percutaneous balloon valvuloplasty was performed at a mean age of 4.0±4.3 days using, on average, a balloon-to-pulmonary annulus ratio of 1.18 mm (with a range from 0.9 to 1.43). Immediate success was achieved in 22/24 patients (92%) with a reduction in the pulmonary transvalvular peak gradient (p<0.05) and in the right ventricle/systemic pressure ratio (p<0.05). There was one death (4%) 6 days after the procedure, and 29.2% of them had transient rhythm complications. For a mean follow-up time of 8.4 years, the re-intervention rate was 42.9%. In total, 14 re-interventions were performed in nine neonates, including surgery in six. Freedom from re-intervention was 50% at 8 years and 43% at 10 and 15 years. CONCLUSION: This series, to the best of our knowledge, has had the longest follow-up of neonates with critical pulmonary valve stenosis. Percutaneous balloon valvuloplasty is a safe and effective treatment, and in our study 75% of the patients were exclusively treated using this technique.

Vascular function long term after Kawasaki disease: another piece of the puzzle?

BACKGROUND: Kawasaki disease is an acute systemic vasculitis. Cardiac complications are frequent and include endothelial dysfunction in patients with coronary anomalies. Thus far, endothelial dysfunction in patients with no coronary lesions is poorly understood. Our aim was to access the vascular function in adolescents and young adults long term after Kawasaki disease, but without coronary aneurysms or any other cardiac risk factors. METHODS: We carried out a single-centre prospective study in a Portuguese population. We evaluated two groups of subjects: (1) Kawasaki disease patients over 11 years of age, diagnosed >5 years ago, with no coronary lesions or any other risk factors for cardiovascular disease; (2) control group of individuals without cardiovascular risk factors. Patients and controls were clinically assessed. Endo-PAT and carotid intima-media thickness assessment were performed to determine vascular function. RESULTS: In total, 43 Kawasaki disease patients were assessed and compared with 43 controls. Kawasaki disease patients presented a decreased reactive hyperaemia index compared with controls (1.59±0.45 versus 1.98±0.41; p<0.001). Augmentation index was similar in both groups (-4.5±7 versus -5±9%; p 0.6). The mean carotid intima-media thickness was not significantly increased in the Kawasaki disease group. There were no statistically significant changes with regard to laboratory data. CONCLUSIONS: Children with Kawasaki disease may have long-term sequelae, even when there is no discernible coronary artery involvement in the acute stage of the disease. Further research is needed to assess whether known strategies to improve endothelial function would bring potential benefits to Kawasaki disease patients.

Percutaneous occlusion of vascular malformations in pediatric and adult patients: 20-year experience of a single center.

OBJECTIVE: A case series on different vascular malformations (VM) treated with percutaneous occlusion in children and adults is presented. BACKGROUND: Percutaneous occlusion is usually the preferred treatment method for VM. Previous series have mostly focused on single types of devices and/or VM. METHODS: Retrospective analysis of all patients who underwent percutaneous occlusion of VM in a single center, from 1995 to 2014, excluding patent ductus arteriosus. Clinical and angiographic data, procedural details, implanted devices, and complications were assessed. Procedural success was defined as effective device deployment with none or minimal residual flow. Predictors of procedural failure and complications were determined by multivariate analysis. RESULTS: A total of 123 VM were intervened in 47 patients with median age of 12 years (25 days-76 years). The VM included 55 pulmonary arteriovenous fistulae, 39 aortopulmonary collaterals, 10 systemic venovenous collaterals, 8 peripheral arteriovenous fistulae, 5 Blalock-Taussig shunts, 4 coronary fistulae, and 2 Fontan fenestrations. The 143 devices used included 80 vascular plugs, 38 coils, 22 duct occluders, and 3 foramen ovale or atrial septal defect occluders. Median vessel size was 4.5 (2.0-16.0) mm and device/vessel size ratio was 1.4 (1.1-2.0). Successful occlusion was achieved in 118 (95.9%) VM, including three reinterventions. Four (3.3%) clinically relevant complications occurred, without permanent sequelae. Lower body weight was independently associated with procedural failure and complications. CONCLUSION: To our knowledge, this is the largest series on different VM occluded percutaneously in children and adults, excluding patent ductus arteriosus. Percutaneous occlusion was effective and safe, using different devices.

Bridging thoracic endovascular aneurysm repair for a late rupture following aortic coarctation angioplasty.

UNLABELLED: Introduction Thoracic endovascular aneurysm repair has been employed to treat late complications after aortic coarctation correction. However, its use in children has seldomly been reported. Case report We present the case of a 15-year-old child who presented with a ruptured aneurysm of the descending aorta complicated later by an aortic-oesophageal fistula following aortic coarctation stenting that was managed with multiple bridging endovascular interventions until a definitive repair was performed. CONCLUSION: Thoracic endovascular aneurysm repair may be used successfully as a bridging intervention to a definitive repair in children with life-threatening aortic complications following aortic coarctation repair.

An insight into the autonomic and haemodynamic mechanisms underlying reflex syncope in children and adolescents: a multiparametric analysis.

Around 15% of children and adolescents experience at least one episode of syncope until adulthood. Excluding cardiac disease, the majority of syncopes are of reflex origin and benign in nature. In this situation, a tilt test is conducted to reproduce symptoms and to evaluate cardiovascular adaptations to orthostatism, but its mechanisms are not yet well defined. Here, we investigated haemodynamics and autonomic activity during tilt in young patients. Patients (n=113) with unexplained syncope were enrolled. Tilt followed a standard protocol without provocative agents. A positive response (fainters) was defined as a sudden development of syncope or presyncope associated with hypotension, bradycardia, or both. Haemodynamic parameters, autonomic activity, and baroreflex sensibility were evaluated. Data were analysed on baseline; immediately after tilting; on tilt adaptation; before fainting or before tilt-down for non-fainters; and on tilt-down. A total of 45 patients experienced syncope after a mean time of 18 minutes. During tilting up, fainters showed lower blood pressure and peripheral resistance values, which decreased progressively with time together with baroreflex sensibility. Sympathetic tone increased massively along time till syncope. No changes in cardiac output and heart rate were observed. Results show a strong effort of the autonomic nervous system to adapt to orthostatic stress through different magnitudes of sympathetic output, which was maximal before syncope without apparent modifications of parasympathetic tone. These changes suggest an imbalance between both branches of the autonomic nervous system, not enabling a time-progressive adaptation and leading the subject to faint.

Initial use of endothelial progenitor cells capturing stents in paediatric congenital heart disease.

INTRODUCTION: Stenosis, mediated by neointimal hyperplasia and thrombosis, is a major limiting factor in successful stent implantation. The introduction of a stent, coated in its endoluminal surface by antihuman CD34 antibodies with endothelial progenitor cell-capturing properties, opens the possibility of promoting a rapid and normal functioning coverage by endothelium and thus avoids both an excessive cell proliferation within stent and the need for long-term dual antiplatelet therapy. These stents, developed for adult coronary artery disease, have not yet been implanted in children or in those with congenital heart disease. OBJECTIVE AND METHODS: In this paper, we describe the implantation of Genous® stents in three children with cyanotic congenital heart disease and obstructed systemic-to-pulmonary shunts. We describe the use of this stent and address its potential feasibility in paediatric congenital heart disease. RESULTS: To maintain the patency of two modified Blalock-Taussig shunts and one ductus arteriosus, four Genous® stents were implanted in three infants with cyanotic heart disease. All procedures were immediately successful, with resolution of stenosis and improvement in transcutaneous oxygen saturation from 66% ± 3.6% to 92% ± 2.6%. In the follow-up, one stent had no occlusion; however, the remaining two had partial occlusion after 5 and 5.5 months, which were successfully managed with balloon dilatation preceding elective definitive surgical correction. CONCLUSION: In our preliminary experience, we demonstrated that Genous® stent implantation was feasible in infants with complex congenital heart disease. Additional studies with larger samples and longer follow-up are required to confirm the potential benefits of this technology in this clinical setting.

Mitro-aortic aneurysms in children: single-centre experience and review of the literature.

OBJECTIVES: This publication aims to report the cases of four children with pseudoaneurysm of the mitral-aortic intervalvular fibrosa and carry out a review of the literature. BACKGROUND: Pseudoaneurysm of the mitral-aortic intervalvular fibrosa is a very rare anomaly in children. It can be either congenital or acquired, namely, after bacterial endocarditis or cardiac trauma. This pathology does not usually cause specific symptoms but its outcome may be potentially fatal. METHODS: We report the cases of four patients presenting with pseudoaneurysm of the mitral-aortic intervalvular fibrosa, referred for treatment in a paediatric cardiology clinic. Patient clinical notes were retrospectively reviewed for aetiology, clinical presentation, diagnostic work-up, surgical treatment, and follow-up. Literature on the subject was extensively reviewed. RESULTS: In three patients, pseudoaneurysm of the mitral-aortic intervalvular fibrosa was acquired, being secondary to bacterial endocarditis in two cases and establishing after mitral surgery in another case. The remaining patient had a "congenital" aetiology - no other cause could be traced. The diagnosis was achieved by transthoracic echocardiography for all patients, and confirmed in all by trans-oesophageal echocardiography, to better define morphological details and to access flow into the aneurysmal formation. All patients were submitted to corrective cardiac surgery. Of the patients, three survived and were cured by surgery, staying asymptomatic, and one died after repeated interventions, for persistent endocarditis. CONCLUSIONS: Pseudoaneurysm of the mitral-aortic intervalvular fibrosa is a rare but potentially fatal anomaly. In our experience, surgical cure was achieved for the majority of the cases, except for a case for which infection could not be locally eradicated, leading to multiple reinterventions.

Multiresistant Kawasaki Disease in a Young Infant with Giant Aneurysms Growing Fast.

BACKGROUND: Kawasaki disease (KD) is a type of vasculitis in which giant coronary artery aneurysms (CAAs) can occur. There are no specific guidelines for managing giant CAAs that develop quickly and are at risk of rupture. Regarding cardiovascular drugs, only beta-blockers are formally recommended in the acute phase of KD. CASE PRESENTATION: A 6-month-old male patient with multiresistant Kawasaki disease and giant CAAs that continued to enlarge after controlling systemic inflammation was examined. The patient required three doses of intravenous immunoglobulin, methylprednisolone pulses, and anakinra and infliximab to normalize systemic inflammation. Due to the rapid increment of aneurysms' dimensions and the risk of rupture, we introduced anticoagulant therapy and propranolol plus captopril, and titration doses were introduced according to a tolerated decrease in heart rate and arterial pressure. CAAs increment stabilized and slowly reduced their dimensions. CONCLUSIONS: The authors describe an atypical case of multiresistant KD with giant rapidly increasing CAAs even after controlling systemic inflammation. The introduction of a beta-blocker and an angiotensin-converting enzyme (ACE) inhibitor was demonstrated to be useful for stabilizing giant CAAs growth and reducing the potential risk of rupture.

Long-term evaluation of endothelial function in Kawasaki disease patients.

BACKGROUND: Kawasaki disease is an acute systemic vasculitis. Cardiac complications are frequent and include endothelial dysfunction in patients with coronary anomalies. So far, the presence of endothelial dysfunction in patients with no coronary lesions has not been demonstrated. Peripheral arterial tonometry (Endo-PAT) measures the microvascular function in response to local ischaemia and has been validated in adult population, but its use in children is scarce. Aim To evaluate endothelial dysfunction in children as a long-term complication after Kawasaki disease using Endo-PAT. METHODS: We evaluated two groups of subjects: (1) Kawasaki disease patients over 11 years of age, diagnosed for >5 years, with no coronary lesions, or any other risk factors for cardiovascular disease; (2) control group of individuals without cardiovascular risk factors. Patients and controls were clinically accessed. Endo-PAT was performed to determine reactive hyperaemia index and augmentation index. RESULTS: A total of 35 individuals (21 males, age 21 ± 6 years) were evaluated (group 1: 19; controls: 16). Kawasaki disease patients presented significant lower reactive hyperaemia index (1.68 ± 0.49 versus 2.31 ± 0.53; p = 0.001). Augmentation index was similar in both groups (-10 ± 7 versus -11 ± 5; p > 0.005). Most patients with Kawasaki disease disclosed endothelial dysfunction (68%) compared with only 12% in controls. CONCLUSIONS: Endo-PAT is feasible and reproducible in the child population. Endothelial dysfunction is a frequent long-term complication in patients after Kawasaki disease with normal appearing coronary arteries. However, these results need validation in a larger population.

The TANGO2 disease and the therapeutic challenge of acute arrhythmia management: a case report.

Background: TANGO2-related metabolic encephalopathy and arrhythmia are a rare, newly recognized, and likely under-diagnosed condition. First described in 2016, it is characterized by developmental delay and recurrent metabolic crisis. During these episodes, patients may present QTc prolongation and ventricular arrhythmias. Case summary: A 13-year-old female, with developmental delay, presented with severe rhabdomyolysis and an initially normal electrocardiogram (ECG). Due to the worsening of rhabdomyolysis, QTc prolongation was identified (QTc 570 ms) and oral ß-blocker therapy started. A non-sustained ventricular tachycardia developed, initially managed with magnesium and lidocaine. After a short period, an arrhythmic storm of polymorphic ventricular extrasystoles induced Torsade de Pointes (TdP) was triggered. A temporary percutaneous pacing lead was placed and esmolol infusion started. The electrical instability ran in parallel with the increasing severity of rhabdomyolysis and systolic ventricular function decline. Genetic testing identified a pathogenic variant in homozygosity in the TANGO2 gene. A stable sinus rhythm was achieved with metabolic and serum electrolytes optimization. ECG showed normalization of the QTc interval. Discussion: The full TANGO2-related phenotype emerges over time and the prognosis is linked to the appearance of ECG abnormalities. QT interval prolongation can lead to life-threatening ventricular tachycardias. The arrhythmia mechanism seems to be secondary to metabolite build-up in cardiomyocytes, which can explain the cardiac phenotype during the crisis which subsides after their resolution. In these patients, avoiding bradycardia is fundamental, since long QT-related TdP seems to be triggered by bradycardia and short-long-short ventricular premature beats (VPB). During an acute metabolic crisis, the management of arrhythmias relies on metabolic control.

Assessing the Genotoxicity of Cellulose Nanomaterials in a Co-Culture of Human Lung Epithelial Cells and Monocyte-Derived Macrophages.

Cellulose micro/nanomaterials (CMNMs) are innovative materials with a wide spectrum of industrial and biomedical applications. Although cellulose has been recognized as a safe material, the unique properties of its nanosized forms have raised concerns about their safety for human health. Genotoxicity is an endpoint that must be assessed to ensure that no carcinogenic risks are associated with exposure to nanomaterials. In this study, we evaluated the genotoxicity of two types of cellulose micro/nanofibrils (CMF and CNF) and one sample of cellulose nanocrystals (CNC), obtained from industrial bleached Eucalyptus globulus kraft pulp. For that, we exposed co-cultures of human alveolar epithelial A549 cells and THP-1 monocyte-derived macrophages to a concentration range of each CMNM and used the micronucleus (MN) and comet assays. Our results showed that only the lowest concentrations of the CMF sample were able to induce DNA strand breaks (FPG-comet assay). However, none of the three CMNMs produced significant chromosomal alterations (MN assay). These findings, together with results from previous in vitro studies using monocultures of A549 cells, indicate that the tested CNF and CNC are not genotoxic under the conditions tested, while the CMF display a low genotoxic potential.

A Rare but Real Necessity: Case Report of Coronary Artery Stenting in an Infant.

Percutaneous coronary intervention (PCI) is an extremely common and well-established procedure in adults which is rarely performed in children. We present a case of a successful left main coronary artery stenting in a small infant with a congenital coronary artery anomaly. We highlight the technical challenges of performing a PCI in a small patient, the risks of antithrombotic prophylaxis in this age group, and the importance of the combined work of the adult and pediatric interventional cardiologist.