Surveillance of adults with congenital heart disease: Current guidelines and actual clinical practice.

BACKGROUND AND AIM: Congenital heart disease (CHD) is the most common birth defect with prevalence of 0.8%. Thanks to tremendous progress in medical and surgical practice, nowadays, >90% of children survive into adulthood. Recently European Society of Cardiology (ESC), American College of Cardiology (ACC)/ American Heart Association (AHA) issued guidelines which offer diagnostic and therapeutic recommendations for the different defect categories. However, the type of technical exams and their frequency of follow-up may vary largely between clinicians and centres. We aimed to present an overview of available diagnostic modalities and describe current surveillance practices by cardiologists taking care of adults with CHD (ACHD). METHODS AND RESULTS: A questionnaire was used to assess the frequency cardiologists treating ACHD for at least one year administrated the most common diagnostic tests for ACHD. The most frequently employed diagnostic modalities were ECG and echocardiography for both mild and moderate/severe CHD. Sixty-seven percent of respondents reported that they routinely address psychosocial well-being. CONCLUSION: Differences exist between reported current clinical practice and published guidelines. This is particularly true for the care of patients with mild lesions. In addition, some differences exist between ESC and American guidelines, with more frequent surveillance suggested by the Americans.

Long term outcome after surgical ASD-closure at young age: Longitudinal follow-up up to 50 years after surgery.

OBJECTIVES: To describe the clinical outcome and quality of life up to 50 years after surgical atrial septal defect (ASD) closure at young age. Primary outcome is defined as MACE (all-cause mortality, cardiac re-interventions, ischemic stroke, endocarditis, heart failure and symptomatic arrhythmia). METHODS: Single-center, longitudinal cohort-study evaluating 135 consecutive patients who underwent ASD-closure before the age of 15 years between 1968 and 1980. Participants were invited for extensive cardiac evaluation and assessment of quality-of-life every 10 years. RESULTS: Eighty patients (86%) of 93 eligible survivors were included in this study (mean age 52 ± 5 years (range 41-63), 40% male). Median follow-up since surgery was 45 years (range 40-51). Cumulative survival after 50 years was 86% and comparable to the normal Dutch population. Cumulative event-free survival after 45 and 50-years was 59% and 46% respectively (re-intervention in 6, symptomatic arrhythmia in 25, and pacemaker implantation in 10 patients). Right ventricular ejection fraction on CMR was diminished in 6%. Exercise capacity was normal in 77%. There was no pulmonary hypertension. NT-proBNP was elevated in 61%. Quality of life was comparable with the general population. No predictors for late events were identified. CONCLUSION: Long-term survival after surgical ASD-closure in childhood is good and not statistically different at 50 years compared to the normal Dutch population. Re-intervention rate is low, there is no pulmonary hypertension. Right ventricular function was diminished in 6%, exercise capacity was good and stable over time with quality of life comparable to the general population. However, supraventricular tachycardia is common.

Preparation and Characterization of Zinc(II)-Based Lewis/Brønsted Acidic Deep Eutectic Solvents.

Lewis/Brønsted acidic deep eutectic solvents (LBDESs) are a recent class of solvents that combine the two types of acidity. In some cases, this synergy leads to enhanced catalytic properties for many reactions and applications. For this reason, it is important to discover more LBDESs. In this work, we prepared and characterized four different zinc(II)-based LBDESs, mixing ZnCl2 and various Brønsted acids: acetic, glycolic, levulinic, and formic acids. Apart from the latter, for which the corresponding DES is not thermally stable, the samples have been characterized in terms of density, viscosity, and conductivity. Notably, as zinc(II) is a diamagnetic metal, all of them are suitable for NMR spectroscopy, for example, for kinetic and mechanistic studies.

Hexavalent chromium release over time from a pyrolyzed Cr-bearing tannery sludge.

Pyrolysis in an inert atmosphere is a widely applied route to convert tannery wastes into reusable materials. In the present study, the Cr(III) conversion into the toxic hexavalent form in the pyrolyzed tannery waste referred to as KEU was investigated. Ageing experiments and leaching tests demonstrated that the Cr(III)-Cr(VI) inter-conversion occurs in the presence of air at ambient temperature, enhanced by wet environmental conditions. Microstructural analysis revealed that the Cr-primary mineral assemblage formed during pyrolysis (Cr-bearing srebrodolskite and Cr-magnetite spinel) destabilized upon spray water cooling in the last stage of the process. In the evolution from the higher to the lower temperature mineralogy, Cr is incorporated into newly formed CrOOH flakes which likely react in air forming extractable Cr(VI) species. This property transforms KEU from an inert waste to a hazardous material when exposed to ordinary ambient conditions.

Life expectancy and end-of-life communication in adult patients with congenital heart disease, 40-53 years after surgery.

Aims: Although survival of patients with congenital heart disease (CHD) improved significantly over time, life expectancy is still not normal. We aimed to investigate how adult patients, their partners, and treating cardiologists estimated the individual life expectancy of CHD patients. Furthermore, preferences regarding end-of-life (EOL) communication were investigated. Methods and results: In this study, we included 202 patients (age: 50 ± 5) who were operated in childhood (<15 years old) between 1968 and 1980 for one of the following diagnoses: atrial septal defect, ventricular septal defect, pulmonary stenosis, tetralogy of Fallot, or transposition of the great arteries. A specific questionnaire was administered to both the patients and their partners, exploring their perceived life expectancy and EOL wishes. Two cardiologists independently assessed the life expectancy of each patient. Most adults with CHD believed their life expectancy to be normal. However, significant differences were found between estimated life expectancy by the cardiologist and patients (female: P = 0.001, male: P = 0.002) with moderate/severe defects, as well as for males with mild defects (P = 0.011). Regarding EOL communication, 85.1% of the patients reported that they never discussed EOL with a healthcare professional. Compared with patients with mild CHD, significantly more patients with moderate/severe defect discussed EOL with a physician (P = 0.011). The wish to discuss EOL with the cardiologist was reported by 49.3% of the patients and 41.7% of their partners. Conclusion: Adult patients, especially with moderate/severe CHD, perceived their life expectancy as normal, whereas cardiologists had a more pessimistic view than their patients. Increased attention is warranted for discussions on life expectancy and EOL to improve patient-tailored care.

Comparison of advanced echocardiographic right ventricular functional parameters with cardiovascular magnetic resonance in adult congenital heart disease.

Aims: Advanced transthoracic echocardiography (TTE) using volumetric and deformational indices provides detailed quantification of right ventricular (RV) function in adults with congenital heart disease (ACHD). Two-dimensional multi-plane echocardiography (2D-MPE) has demonstrated regional wall differences in RV longitudinal strain (LS). This study aims to evaluate the association of these parameters with cardiovascular magnetic resonance (CMR). Methods and results: One-hundred stable ACHD patients with primarily affected RVs were included (age 50 ± 5 years; 53% male). Conventional and advanced echocardiographic RV functional parameters were compared with CMR-derived RV function. Advanced echocardiographic RV functional parameters were measurable in approximately one-half of the study cohort, while multi-wall LS assessment feasibility was lower. CMR RV ejection fraction (CMR-RVEF) was moderately correlated with deformational, area, and volumetric parameters [RV global LS (lateral wall and septum), n = 55: r = -0.62, P < 0.001; RV wall average LS, n = 34: r = -0.49, P = 0.002; RV lateral wall LS, n = 56: r = -0.45, P < 0.001; fractional area change, n = 67: r = 0.48, P < 0.001; 3D-RVEF, n = 48: r = 0.40, P = 0.005]. Conventional measurements such as TAPSE and RV S' correlated poorly. RV global LS best identified CMR-RVEF < 45% (area under the curve: 0.84, P < 0.001: cut-off value -19%: sensitivity 100%, specificity 57%). RVEF and LS values were significantly higher when measured by CMR compared with TTE (mean difference RVEF: 5 [-9 to 18] %; lateral (free) wall LS: -7 [7 to -21] %; RV global LS: -6 [5 to -16] %) while there was no association between respective LS values. Conclusion: In ACHD patients, advanced echocardiographic RV functional parameters are moderately correlated with CMR-RVEF, although significant differences exist between indices measurable by both modalities.

A circular dichroism study of the protective role of polyphosphoesters polymer chains in polyphosphoester-myoglobin conjugates.

Protein-polymer conjugates are a blooming class of hybrid systems with high biomedical potential. Despite a plethora of papers on their biomedical properties, the physical-chemical characterization of many protein-polymer conjugates is missing. Here, we evaluated the thermal stability of a set of fully-degradable polyphosphoester-protein conjugates by variable temperature circular dichroism, a common but powerful technique. We extensively describe their thermodynamic stability in different environments (in physiological buffer or in presence of chemical denaturants, e.g., acid or urea), highlighting the protective role of the polymer in preserving the protein from denaturation. For the first time, we propose a simple but effective protocol to achieve useful information on these systems in vitro, useful to screen new samples in their early stages.

Blood Compatibility of Hydrophilic Polyphosphoesters.

Polyphosphoesters (PPEs) are a class of versatile degradable polymers. Despite the high potential of this class of polymers in biomedical applications, little is known about their blood interaction and compatibility. We evaluated the hemocompatibility of water-soluble PPEs (with different hydrophilicities and molar masses) and PPE-coated model nanocarriers. Overall, we identified high hemocompatibility of PPEs, comparable to poly(ethylene glycol) (PEG), currently used for many applications in nanomedicine. Hydrophilic PPEs caused no significant changes in blood coagulation, negligible platelet activation, the absence of red blood cells lysis, or aggregation. However, when a more hydrophobic copolymer was studied, some changes in the whole blood clot strength at the highest concentration were detected, but only concentrations above that are typically used for biomedical applications. Also, the PPE-coated model nanocarriers showed high hemocompatibility. These results contribute to defining hydrophilic PPEs as a promising platform for degradable and biocompatible materials in the biomedical field.

Amphiphilic Polyphosphonate Copolymers as New Additives for PDMS-Based Antifouling Coatings.

Poly(ethyl ethylene phosphonate)-based methacrylic copolymers containing polysiloxane methacrylate (SiMA) co-units are proposed as surface-active additives as alternative solutions to the more investigated polyzwitterionic and polyethylene glycol counterparts for the fabrication of novel PDMS-based coatings for marine antifouling applications. In particular, the same hydrophobic SiMA macromonomer was copolymerized with a methacrylate carrying a poly(ethyl ethylene phosphonate) (PEtEPMA), a phosphorylcholine (MPC), and a poly(ethylene glycol) (PEGMA) side chain to obtain non-water soluble copolymers with similar mole content of the different hydrophilic units. The hydrolysis of poly(ethyl ethylene phosphonate)-based polymers was also studied in conditions similar to those of the marine environment to investigate their potential as erodible films. Copolymers of the three classes were blended into a condensation cure PDMS matrix in two different loadings (10 and 20 wt%) to prepare the top-coat of three-layer films to be subjected to wettability analysis and bioassays with marine model organisms. Water contact angle measurements showed that all of the films underwent surface reconstruction upon prolonged immersion in water, becoming much more hydrophilic. Interestingly, the extent of surface modification appeared to be affected by the type of hydrophilic units, showing a tendency to increase according to the order PEGMA < MPC < PEtEPMA. Biological tests showed that Ficopomatus enigmaticus release was maximized on the most hydrophilic film containing 10 wt% of the PEtEP-based copolymer. Moreover, coatings with a 10 wt% loading of the copolymer performed better than those containing 20 wt% for the removal of both Ficopomatus and Navicula, independent from the copolymer nature.

One-Pot Process: Microwave-Assisted Keratin Extraction and Direct Electrospinning to Obtain Keratin-Based Bioplastic.

Poultry feathers are among the most abundant and polluting keratin-rich waste biomasses. In this work, we developed a one-pot microwave-assisted process for eco-friendly keratin extraction from poultry feathers followed by a direct electrospinning (ES) of the raw extract, without further purification, to obtain keratin-based bioplastics. This microwave-assisted keratin extraction (MAE) was conducted in acetic acid 70% v/v. The effects of extraction time, solvent/feathers ratio, and heating mode (MAE vs. conventional heating) on the extraction yield were investigated. The highest keratin yield (26 ± 1% w/w with respect to initial feathers) was obtained after 5 h of MAE. Waste-derived keratin were blended with gelatin to fabricate keratin-based biodegradable and biocompatible bioplastics via ES, using 3-(Glycidyloxypropyl)trimethoxysilane (GPTMS) as a cross-linking agent. A full characterization of their thermal, mechanical, and barrier properties was performed by differential scanning calorimetry, thermogravimetric analysis, uniaxial tensile tests, and water permeability measurements. Their morphology and protein structure were investigated using scanning electron microscopy and attenuated total reflection-infrared spectroscopy. All these characterizations highlighted that the properties of the keratin-based bioplastics can be modulated by changing keratin and GPTMS concentrations. These bioplastics could be applied in areas such as bio-packaging and filtration/purification membranes.

Efficacy of Unsupervised Self-Collected Mid-Turbinate FLOQSwabs for the Diagnosis of Coronavirus Disease 2019 (COVID-19).

CONTEXT: The Global Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic has resulted in explosive patterns of transmission in most countries. Nasopharyngeal swabs were the specimen's collection tools recommended for the diagnosis of SARS-CoV-2 infection, and for monitoring infection outbreaks in communities. Our objective was to report the quality and efficacy of unsupervised self-collected mid turbinate "dry FLOQSwabs" (MT FLOQSwabs) (56380CS01, Copan). There were 111 specimens collected for the study: 36 by health care personnel, from themselves, to verify the quality and efficacy of mid-turbinate swabs; 75 to compare and assess the diagnostic performance, among health care personnel, of nasopharyngeal swabs and self-collected mid-turbinate FLOQSwabs. A collection of 51 specimens was enrolled to define the efficacy of the Testami program (validation). Our analyses demonstrate that self-collected mid-turbinate dry swabs ensure an accuracy of 97.3%, as compared to the standard nasopharyngeal swabs collected by health care workers. Furthermore, the mid-turbinate FLOQSwabs can be stored without medium for six days at room temperature without affecting the molecular diagnosis of the SARS-CoV-2 virus infection. Self-collection of diagnostic specimens at home could offer an avenue to increase testing availability for SARS-CoV-2 infection without asking people to travel to a clinic or a laboratory, thus reducing people's exposure to infection. Our findings demonstrate that unsupervised self-collection swabs, transported dry, are sensitive, practical and easy-to-use tools and should be considered for diagnosis of SARS-COV-2 and coronavirus disease 2019 (COVID-19) surveillance.

Thermodynamic Evaluation of the Interactions between Anticancer Pt(II) Complexes and Model Proteins.

In this work, we have analysed the binding of the Pt(II) complexes ([PtCl(4'-phenyl-2,2':6',2″-terpyridine)](CF3SO3) (1), [PtI(4'-phenyl-2,2':6',2″-terpyridine)](CF3SO3) (2) and [PtCl(1,3-di(2-pyridyl)benzene) (3)] with selected model proteins (hen egg-white lysozyme, HEWL, and ribonuclease A, RNase A). Platinum coordination compounds are intensively studied to develop improved anticancer agents. In this regard, a critical issue is the possible role of Pt-protein interactions in their mechanisms of action. Multiple techniques such as differential scanning calorimetry (DSC), electrospray ionization mass spectrometry (ESI-MS) and UV-Vis absorbance titrations were used to enlighten the details of the binding to the different biosubstrates. On the one hand, it may be concluded that the affinity of 3 for the proteins is low. On the other hand, 1 and 2 strongly bind them, but with major binding mode differences when switching from HEWL to RNase A. Both 1 and 2 bind to HEWL with a non-specific (DSC) and non-covalent (ESI-MS) binding mode, dominated by a 1:1 binding stoichiometry (UV-Vis). ESI-MS data indicate a protein-driven chloride loss that does not convert into a covalent bond, likely due to the unfavourable complexes' geometries and steric hindrance. This result, together with the significant changes of the absorbance profiles of the complex upon interaction, suggest an electrostatic binding mode supported by some stacking interaction of the aromatic ligand. Very differently, in the case of RNase A, slow formation of covalent adducts occurs (DSC, ESI-MS). The reactivity is higher for the iodo-compound 2, in agreement with iodine lability higher than chlorine.

Effect of Polymer Hydrophilicity and Molar Mass on the Properties of the Protein in Protein-Polymer Conjugates: The Case of PPEylated Myoglobin.

Polyphosphoesters (PPEs), a versatile class of biodegradable and biocompatible polymers, have been proposed as alternatives to poly(ethylene glycol) (PEG), which is suspected to be responsible for anaphylactic reactions in some patients after the administration of PEGylated compounds, e.g., in the current Covid-19 vaccines. We present the synthesis and characterization of a novel set of protein-polymer conjugates using the model protein myoglobin and a set of PPEs with different hydrophilicity and molar mass. We report an extensive evaluation of the (bio)physical properties of the protein within the conjugates, studying its conformation, residual activity, and thermal stability by complementary techniques (UV-vis spectroscopy, nano-differential scanning calorimetry, and fluorometry). The data underline the systematic influence of polymer hydrophilicity on protein properties. The more hydrophobic polymers destabilize the protein, the more hydrophilic PPEs protect against thermally induced aggregation and proteolytic degradation. This basic study aims at guiding the design of future PPEylated drugs and protein conjugates.

Insight into Protein-Polymer Conjugate Relaxation Dynamics: The Importance of Polymer Grafting.

The bio and chemical physics of protein-polymer conjugates are related to parameters that characterize each component. With this work, it is intended to feature the dynamical properties of the protein-polymer conjugate myoglobin (Mb)-poly(ethyl ethylene phosphate), in the ps and ns time scales, in order to understand the respective roles of the protein and of the polymer size in the dynamics of the conjugate. Elastic and quasi-elastic neutron scattering is performed on completely hydrogenated samples with variable number of polymer chains covalently attached to the protein. The role of the polymer length in the protein solvation and internal dynamics is investigated using two conjugates formed by polymers of different molecular weight. It is confirmed that the flexibility of the complex increases with the number of grafted polymer chains and that a sharp dynamical transition appears when either grafting density or polymer molecular weight are high. It is shown that protein size is crucial for the polymer structural organization and interaction on the protein surface and it is established that the glass properties of the polymer change upon conjugation. The results give a better insight of the equivalence of the polymer coating and the role of water on the surface of proteins.