Outcomes of transcatheter pulmonary SAPIEN 3 valve implantation: an international registry.

BACKGROUND AND AIMS: Transcatheter pulmonary valve implantation (TPVI) is indicated to treat right-ventricular outflow tract (RVOT) dysfunction related to congenital heart disease (CHD). Outcomes of TPVI with the SAPIEN 3 valve that are insufficiently documented were investigated in the EUROPULMS3 registry of SAPIEN 3-TPVI. METHODS: Patient-related, procedural, and follow-up outcome data were retrospectively assessed in this observational cohort from 35 centres in 15 countries. RESULTS: Data for 840 consecutive patients treated in 2014-2021 at a median age of 29.2 (19.0-41.6) years were obtained. The most common diagnosis was conotruncal defect (70.5%), with a native or patched RVOT in 50.7% of all patients. Valve sizes were 20, 23, 26, and 29 mm in 0.4%, 25.5%, 32.1%, and 42.0% of patients, respectively. Valve implantation was successful in 98.5% [95% confidence interval (CI), 97.4%-99.2%] of patients. Median follow-up was 20.3 (7.1-38.4) months. Eight patients experienced infective endocarditis; 11 required pulmonary valve replacement, with a lower incidence for larger valves (P = .009), and four experienced pulmonary valve thrombosis, including one who died and three who recovered with anticoagulation. Cumulative incidences (95%CI) 1, 3, and 6 years after TPVI were as follows: infective endocarditis, 0.5% (0.0%-1.0%), 0.9% (0.2%-1.6%), and 3.8% (0.0%-8.4%); pulmonary valve replacement, 0.4% (0.0%-0.8%), 1.3% (0.2%-2.4%), and 8.0% (1.2%-14.8%); and pulmonary valve thrombosis, 0.4% (0.0%-0.9%), 0.7% (0.0%-1.3%), and 0.7% (0.0%-1.3%), respectively. CONCLUSIONS: Outcomes of SAPIEN 3 TPVI were favourable in patients with CHD, half of whom had native or patched RVOTs.

Molecular and Biochemical Evidence of the Toxic Effects of Terbuthylazine and Malathion in Zebrafish.

Our research sought to determine the molecular and biochemical effects of environmentally relevant exposure to commonly used chloro-s-triazine herbicide terbuthylazine and organophosphate insecticide malathion on zebrafish. To this aim, mature zebrafish were exposed to 2 and 30 µg L-1 terbuthylazine and 5 and 50 µg L-1 malathion alone and in combination for 14 days. Aside from the accumulation of TBARS and protein carbonyls, a decrease in antioxidants and succinate dehydrogenase activity, an increase in oxidized glutathione, and enhanced apoptosis via Caspase-3 and BAX overexpression were observed. Furthermore, terbuthylazine and malathion induced mitochondrial swelling (up to 210% after single exposure and up to 470% after co-exposure) and lactate dehydrogenase leakage (up to 268% after single exposure and up to 570% after co-exposure) in a concentration-dependent manner. Significant upregulation of ubiquitin expression and increased cathepsin D activity were characteristics that appeared only upon terbuthylazine exposure, whereas the induction of IgM was identified as the specific characteristic of malathion toxicity. Meanwhile, no alterations in the zebrafish hypothalamic-pituitary-thyroid axis was observed. Co-exposure increased the adverse effects of individual pesticides on zebrafish. This study should improve the understanding of the mechanisms of pesticide toxicity that lead to fish impairment and biodiversity decline.

Pesticide Pollution: Detrimental Outcomes and Possible Mechanisms of Fish Exposure to Common Organophosphates and Triazines.

Pesticides are well known for their high levels of persistence and ubiquity in the environment, and because of their capacity to bioaccumulate and disrupt the food chain, they pose a risk to animals and humans. With a focus on organophosphate and triazine pesticides, the present review aims to describe the current state of knowledge regarding spatial distribution, bioaccumulation, and mode of action of frequently used pesticides. We discuss the processes by which pesticides and their active residues are accumulated and bioconcentrated in fish, as well as the toxic mechanisms involved, including biological redox activity, immunotoxicity, neuroendocrine disorders, and cytotoxicity, which is manifested in oxidative stress, lysosomal and mitochondrial damage, inflammation, and apoptosis/autophagy. We also explore potential research strategies to close the gaps in our understanding of the toxicity and environmental risk assessment of organophosphate and triazine pesticides.

Toxic effects and mechanisms of common pesticides (Roundup and chlorpyrifos) and their mixtures in a zebrafish model (Danio rerio).

Agrochemicals can adversely affect biodiversity, environment and human health, and commonly occur in mixtures with poorly characterized toxic mechanisms and health hazards. Here, we evaluated the individual and mixture toxicities of Roundup and chlorpyrifos in environmentally relevant concentrations to zebrafish using molecular and biochemical indices. Studied pesticides alone and in combination caused depletion of total antioxidant capacity and cellular thiols, overproduction of ROS, accumulation of oxidative lesions and elevated DNA damage in zebrafish liver. Notably, low concentration of Roundup induced a hormesis-like effect by stimulating the protective cellular mechanisms. Chlorpyrifos showed stronger prooxidant effects than Roundup and additionally caused nitrosative and carbonyl stress in zebrafish. At the organismal level, studied pesticides and their mixtures induced hepato- and neurotoxicity. The effects of the studied pesticides on biomarkers of apoptosis, endocrine disruption and immune disorders were generally weak and inconsistent. The multibiomarker assessment showed that chlorpyrifos is considerably more toxic than Roundup to zebrafish. The toxic effects of the pesticide mixtures were mostly driven by chlorpyrifos, with minimal or mitigating effects of Roundup addition. These findings elucidate the toxic mechanisms of common pesticides in a model vertebrate and demonstrate that health hazards of pesticide mixtures cannot be predicted from the effects of single pesticides.

Increased incidence of coronary artery origin anomalies associated with isolated patent ductus arteriosus.

Coronary artery anomalies may increase the risk of sudden death. Despite awareness of this association with certain congenital heart anomalies such as tetralogy of Fallot and transposition of the great arteries, it is thought to be an infrequent finding in cases of isolated patent ductus arteriosus (PDA). The authors report their experience with coronary anomalies in PDA patients. This study aimed to estimate the incidence of coronary artery anomalies in patients with PDA. The study reviewed 206 angiograms of PDA patients obtained between 1999 and 2011 to determine the origin of the coronary arteries. In 102 angiograms (49.5 %), the origin of the coronary arteries could be adequately visualized. An anomalous origin of coronary arteries was detected in 11 of the 102 patients (10.8 %). Seven of these patients had a single common coronary artery origin (6.8 %). One patient had an aberrant origin of the left coronary artery from the noncoronary sinus, and three patients had an aberrant origin of the right coronary artery: two from the left coronary sinus and one from the noncoronary sinus. These findings suggest that the incidence of coronary artery anomalies in association with an isolated PDA may be considerably higher than expected and previously reported. In view of the increased risk for sudden death with coronary anomalies, a reasonable approach is to determine the coronary artery origin and pathway after the diagnosis of an isolated PDA.

Transcatheter closure of ruptured right-coronary aortic sinus fistula to right ventricle.

A 22-year-old man was referred for evaluation of exertional fatigue. On examination, there were no overt signs of congestive heart failure. Transthoracic and transesophageal echocardiography revealed rupture of the right coronary aortic sinus of Valsalva into the right ventricle. It was successfully closed with a 12 × 10 Amplatzer duct occluder.

MEFV, TNF1rA, CARD15 and NLRP3 mutation analysis in PFAPA.

PFAPA is a periodic fever disease, of unknown etiology, characterized by aphthous stomatitis, pharyngitis and cervical adenitis. To inquire whether genes implicated in other auto-inflammatory diseases might be involved in its pathogenesis, predominant mutations in the genes causing familial Mediterranean fever, TNF receptor-associated periodic fever syndrome, Crohn's disease and Muckel-Wells syndrome were analyzed in PFAPA patients. Patients (n = 57) with PFAPA, according to previously published criteria were recruited, at the Meyer Children Hospital during 2006-2007. Clinical information was complemented during physicians-parents encounter. Predominant mutations in MEFV, TNF1rA, CARD15/NOD2 and NLRP3 genes were tested. Mean age at diagnosis was 30.64 +/- 16.4 months. Boys (n = 33; 58%) were diagnosed earlier than girls (n = 21; 42%) at 26.18 +/- 13.83 and 36.41 +/- 18.32 months, respectively (P = 0.05). Fifteen patients (27%) carried an MEFV mutation; two patients (3.6%) a CARD15 mutation, one patient (1.8%) a variance in TNF1rA and another had both an MEFV and a CARD15 mutation. Clinical symptoms were equally manifested in carriers and non-carriers. The high carrier rate of MEFV mutations in our PFAPA cases compares well with that of the general population in Israel. It is debated whether MEFV mutations, when mediated by the presence of additional modifiers, may expose a transient fever condition, namely PFAPA.

Intra-familial clinical heterogeneity: absence of genotype-phenotype correlation in primary hyperoxaluria type 1 in Israel.

BACKGROUND/AIMS: Primary hyperoxaluria type 1 (PH1) is caused by the deficiency of the liver enzyme alanine:glyoxylate aminotransferase which results in increased synthesis and excretion of oxalate. The clinical manifestations of PH1 are heterogeneous with respect to the age of onset and rate of progression. The aim of this study was to investigate possible relationships between a given genotype, the biochemical profile and the clinical phenotype. METHODS: We conducted a study of 56 patients from 22 families with PH1 from Israel. The clinical and biochemical data were compiled and the genotype was determined for each family. RESULTS: The prevalent phenotype was of early onset with progression to end-stage renal disease during the first decade of life. Fifteen PH1-causing mutations were detected in 21 families: 10 were first described in this patient population. Marked intra-familial clinical heterogeneity was noted, meaning that there was no correlation between a given genotype and the phenotype. CONCLUSIONS: The clinical course of patients with PH1 is not dictated primarily by its genotype. Other genetic and/or environmental factors play a role in determining the ultimate phenotype.