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Background: There is little data on the outcome of balloon aortic valvuloplasty (BAV) in relation to valve dimensions and calcification patterns. The procedure is not standardized, particularly the choice of balloon size., Methods: This retrospective multicenter study focused on BAV efficacy and safety by analyzing the relationship between balloon size, annulus geometry (i.e., diameters, perimeter, and area), and calcification patterns (total burden and calcium distribution over each individual leaflet). From March 2018 to March 2023, all consecutive patients who underwent clinically indicated BAV and ECG-gated multidetector computed tomography of the aorta were included, except those with a bicuspid valve. Calcium score was calculated on contrast-enhanced images based on a luminal attenuation threshold of +100 HU., Results: One hundred and fifteen patients were included. Procedural success was 82.6 %. The balloon-to-annulus ratio (BAR) relative to diameter, perimeter, and area was higher in patients with successful BAV. Patients with unsuccessful BAV had a significantly higher aortic valve calcium burden. The complication rate was 4.3 % and there was no association with valve geometry or calcium burden. A trend towards a reduced complication rate was found as calcium asymmetry increased. BAR minimum annulus diameter was the best parameter in predicting procedural success, with a cut-off at 0.85., Conclusions: BAV efficacy is correlated directly with balloon size in relation to annulus dimension and inversely with total calcium burden. The minimum diameter of the valve may be adopted as a reference for balloon sizing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Varicocele is a prevalent condition in the infertile male population. However, to date, which patients may benefit most from varicocele repair is still a matter of debate. The purpose of this study was to evaluate whether certain preintervention sperm parameters are predictive of successful varicocele repair, defined as an improvement in total motile sperm count (TMSC). We performed a retrospective study on 111 patients with varicocele who had undergone varicocele repair, collected from the Department of Endocrinology, Metabolic Diseases and Nutrition, University of Catania (Catania, Italy), and the Unit of Urology at the Selcuk University School of Medicine (Konya, Türkiye). The predictive analysis was conducted through the use of the Brain Project, an innovative tool that allows a complete and totally unbiased search of mathematical expressions that relate the object of study to the various parameters available. Varicocele repair was considered successful when TMSC increased by at least 50% of the preintervention value. For patients with preintervention TMSC below 5 × 106, improvement was considered clinically relevant when the increase exceeded 50% and the absolute TMSC value was >5 × 106. From the preintervention TMSC alone, we found a model that predicts patients who appear to benefit little from varicocele repair with a sensitivity of 50.0% and a specificity of 81.8%. Varicocele grade and serum follicle-stimulating hormone (FSH) levels did not play a predictive role, but it should be noted that all patients enrolled in this study were selected with intermediate- or high-grade varicocele and normal FSH levels. In conclusion, preintervention TMSC is predictive of the success of varicocele repair in terms of TMSC improvement in patients with intermediate- or high-grade varicoceles and normal FSH levels., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Takotsubo syndrome (TTS) is a rare disease mimicking acute coronary syndrome, often triggered by physical or emotional stress, and characterized by transient left ventricular dysfunction. Recurrences are described in about 5% of cases and may have different clinical and imaging patterns. In the present report, SARS-COV-2 infection, even in the absence of symptoms and overt emotional stress, seems correlated with recurrence of TTS, due to the absence of other recognized triggers. The hypothesis is that in predisposed patients, events like catecholamine-induced myocyte injury, direct viral damage, cytokine storm, immune-mediated damage, and procoagulant state, all possibly induced by the infection, may elicit endothelial dysfunction as substrate for TTS onset., Competing Interests: The authors declare the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Dall'Ara, Compagnone, Carletti, Piciucchi, Gardini and Galvani.)

Background: Few data are available about the durability of the response, the induction of neutralizing antibodies, and the cellular response upon the third dose of the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in hemato-oncological patients., Objective: To investigate the antibody and cellular response to the BNT162b2 vaccine in patients with hematological malignancy., Methods: We measured SARS-CoV-2 anti-spike antibodies, anti- Omicron neutralizing antibodies, and T-cell responses 1 month after the third dose of vaccine in 93 fragile patients with hematological malignancy (FHM), 51 fragile not oncological subjects (FNO) aged 80-92, and 47 employees of the hospital (healthcare workers, (HW), aged 23-66 years. Blood samples were collected at day 0 (T0), 21 (T1), 35 (T2), 84 (T3), 168 (T4), 351 (T pre-3D), and 381 (T post-3D) after the first dose of vaccine. Serum IgG antibodies against S1/S2 antigens of SARS-CoV-2 spike protein were measured at every time point. Neutralizing antibodies were measured at T2, T3 (anti-Alpha), T4 (anti-Delta), and T post-3D (anti- Omicron ). T cell response was assessed at T post-3D., Results: An increase in anti-S1/S2 antigen antibodies compared to T0 was observed in the three groups at T post-3D. After the third vaccine dose, the median antibody level of FHM subjects was higher than after the second dose and above the putative protection threshold, although lower than in the other groups. The neutralizing activity of antibodies against the Omicron variant of the virus was tested at T2 and T post-3D. 42.3% of FHM, 80,0% of FNO, and 90,0% of HW had anti- Omicron neutralizing antibodies at T post-3D. To get more insight into the breadth of antibody responses, we analyzed neutralizing capacity against BA.4/BA.5, BF.7, BQ.1, XBB.1.5 since also for the Omicron variants, different mutations have been reported especially for the spike protein. The memory T-cell response was lower in FHM than in FNO and HW cohorts. Data on breakthrough infections and deaths suggested that the positivity threshold of the test is protective after the third dose of the vaccine in all cohorts., Conclusion: FHM have a relevant response to the BNT162b2 vaccine, with increasing antibody levels after the third dose coupled with, although low, a T-cell response. FHM need repeated vaccine doses to attain a protective immunological response., Competing Interests: Author MC is employed in Neomatrix, Rome, Italy. EPi is employed in Takis, Rome, Italy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Laquintana, Mottini, Marchesi, Marcozzi, Terrenato, Sperandio, de Latouliere, Carrieri, Pimpinelli, Pontone, Pellini, Campo, Conti, Accetta, Mandoj, Petrone, Di Bella, Vujovic, Morrone, Compagnone, Principato, Pinto, Papa, Falcucci, La Malfa, Pallocca, De Marco, Piaggio, Ciliberto, Mengarelli and di Martino.)

The COVID-19 pandemic, once a global crisis, is now largely under control, a testament to the extraordinary global efforts involving vaccination and public health measures. However, the relentless evolution of SARS-CoV-2, leading to the emergence of new variants, continues to underscore the importance of remaining vigilant and adaptable. Monoclonal antibodies (mAbs) have stood out as a powerful and immediate therapeutic response to COVID-19. Despite the success of mAbs, the evolution of SARS-CoV-2 continues to pose challenges and the available antibodies are no longer effective. New variants require the ongoing development of effective antibodies. In the present study, we describe the generation and characterization of neutralizing mAbs against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein by combining plasmid DNA and recombinant protein vaccination. By integrating genetic immunization for rapid antibody production and the potent immune stimulation enabled by protein vaccination, we produced a rich pool of antibodies, each with unique binding and neutralizing specificities, tested with the ELISA, BLI and FACS assays and the pseudovirus assay, respectively. Here, we present a panel of mAbs effective against the SARS-CoV-2 variants up to Omicron BA.1 and BA.5, with the flexibility to target emerging variants. This approach ensures the preparedness principle is in place to address SARS-CoV-2 actual and future infections.

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

This study explores an eco-friendly method for recovering platinum group metals from a synthetic automotive three-way catalyst (TWC). Bioleaching of palladium (Pd) using the thiosulfate-copper-ammonia leaching processes, with biogenic thiosulfate sourced from a bioreactor used for biogas biodesulfurization, is proposed as a sustainable alternative to conventional methods. Biogenic thiosulfate production was optimized in a gas-lift bioreactor by studying the pH (8-10) and operation modes (batch and continuous) under anoxic and microaerobic conditions for 35 d. The maximum concentration of 4.9 g S 2 O 3 2- L -1 of biogenic thiosulfate was reached under optimal conditions (batch mode, pH = 10, and airflow rate 0.033 vvm). To optimize Pd bioleaching from a ground TWC, screening through a Plackett-Burman design determined that oxygen and temperature significantly affected the leaching yield negatively and positively, respectively. Based on these results, an optimization through an experimental design was performed, indicating the optimal conditions to be Na 2 S 2 1.2 M, CuSO 3 0.03 M, (NH 4 0.03 M, (NH 4 ) 2 1.5 M, Na 4 1.5 M, Na 2 0.2 M, pH 8, and 60 °C. A remarkable 96.2 and 93.2% of the total Pd was successfully extracted from the solid at 5% pulp density using both commercially available and biogenic thiosulfate, highlighting the method's versatility for Pd bioleaching from both thiosulfate sources.3 0.2 M, pH 8, and 60 °C. A remarkable 96.2 and 93.2% of the total Pd was successfully extracted from the solid at 5% pulp density using both commercially available and biogenic thiosulfate, highlighting the method's versatility for Pd bioleaching from both thiosulfate sources.

Acid bioleaching of Al by Acidithiobacillus thiooxidans has been explored as an environmentally friendly pretreatment to facilitate the extraction of platinum group metals from spent three-way catalysts (TWC). Biogenic sulfur obtained from desulfurization bioreactors improved the production of acid by A. thiooxidans compared to commercially available elemental sulfur. The lixiviation abilities of bacteria-free biogenic acid and biogenic acid with exponential or stationary phase bacteria were compared against a control batch produced by commercial H 2 SO 4 . The maximum Al leaching percentage (54.5%) was achieved using biogenic acids with stationary-phase bacteria at a TWC pulp density of 5% w/v whereas bacteria-free biogenic acid (23.4%), biogenic acid with exponential phase bacteria (21.7%) and commercial H 2 SO 4 (24.7%) showed lower leaching abilities. The effect of different pulp densities of ground TWC (5, 30, and 60% w/v) on Al leaching and bacterial growth was determined. While greater Al leaching yields were obtained at lower TWC pulp density solutions (54.5% at 5% w/v and 2.5% at 60% w/v), higher pulp densities enhanced microbial growth (2.3 × 10 9  cells/mL at 5% w/v and 9.5 × 10 10  cells/mL at 60% w/v). The dissolution of the metal from the solid into the liquid phase triggered the production of biological polymeric substances that were able to absorb traces of both Al (up to 24.80% at 5% w/v) and Pt (up to 0.40% at 60% w/v)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In the first report from the MitraBridge registry, MitraClip as a bridge to heart transplantation (HTx) proved to be at 1-year an effective treatment strategy for 119 patients with advanced heart failure (HF) who were potential candidates for HTx. We aimed to determine if benefits of MitraClip procedure as a bridge-to-transplant persist up to 2-years., Methods: By the end of the enrollment period, a total of 153 advanced HF patients (median age 59 years, left ventricular ejection fraction 26.9 ± 7.7%) with significant secondary mitral regurgitation, who were potential candidates for HTx and were treated with MitraClip as a bridge-to-transplant strategy, were included in the MitraBridge registry. The primary endpoint was the 2-year composite adverse events rate of all-cause death, first hospitalization for HF, urgent HTx or LVAD implantation., Results: Procedural success was achieved in 89.5% of cases. Thirty-day mortality was 0%. At 2-year, Kaplan-Meier estimates of freedom from primary endpoint was 47%. Through 24 months, the annualized rate of HF rehospitalization per patient-year was 44%. After an overall median follow-up time of 26 (9-52) months, elective HTx was successfully performed in 30 cases (21%), 19 patients (13.5%) maintained or obtained the eligibility for transplant, and 32 patients (22.5%) no longer had an indication for HTx because of significant clinical improvement., Conclusions: After 2-years of follow-up, the use of MitraClip as a bridge-to-transplant was confirmed as an effective strategy, allowing elective HTx or eligibility for transplant in one third of patients, and no more need for transplantation in 22.5% of cases., Competing Interests: Declaration of Competing Interest A.S. has served as a consultant and received consulting fees from NeoChord Inc.; R.E.L. received speaker fees from Abbott, Boston and Edwards; M.A. received speaker fees from Abbott Vascular and Medtronic; P.G. has been a proctor for Abbot; N.M.V.M. received research grant support from Abbott Vascular, Biotronik, Medtronik, Boston Scientific, Edwards Lifesciences, Daiichi Sankyo, Abiomed en PulseCath BV; F.S. received consultancy and lecture's fees from Abbott and Edwards., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Over the past decades, the improvements in the diagnostic power and availability of non-invasive cardiac imaging techniques have led to a decline of right heart catheterization (RHC) performance. However, RHC remains the gold standard for diagnosing pulmonary hypertension and an essential tool for the evaluation of patient candidacy to heart transplantation., Methods: This survey was carried out jointly by the Young Committee of GISE, with the support of the SICI-GISE Society, and the ICOT group, with the aim of evaluating how the interventional cardiology community perform RHC. A web-based questionnaire based on 20 questions was distributed to SICI-GISE members., Results: The survey was distributed to 1550 physicians with 174 (11%) responses. Most centers perform few procedures per year (<10 RHC/year) and a dedicated cardiologist is usually lacking. Patients were frequently admitted as ordinary hospitalization regimen and the most frequent indication for RHC was the hemodynamic assessment of pulmonary hypertension, followed by diagnostics of valvular diseases and advanced heart failure/heart transplantation. Indeed, the majority of participants (86%) are involved in transcatheter procedures for structural heart disease. The average time taken to perform the RHC was approximately 30-60 min. The femoral access (60%) was the most frequently used, usually by an echo-guided approach. Two-thirds of participants discontinued oral anticoagulant therapy before RHC. Only 27% of centers assess wedge position from an integrated analysis. Furthermore, the edge pressure is detected in the end-diastolic cardiac phase in half cases and in the end-expiratory phase in only 31%. The most commonly used method for cardiac output calculation was the indirect Fick method (58%)., Conclusions: Guidance on the best practice for performing RHC is currently lacking. A more precise standardization of this demanding procedure is warranted.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused more than 760 million cases and over 6.8 million deaths as of March 2023. Vaccination has been the main strategy used to contain the spread of the virus and to prevent hospitalizations and deaths. Currently, two mRNA-based vaccines and one adenovirus-vectored vaccine have been approved and are available for use in the U.S. population. The versatility, low cost, and rapid production of DNA vaccines provide important advantages over other platforms. Additionally, DNA vaccines efficiently induce both B- and T-cell responses by expressing the antigen within transfected host cells, and the antigen, after being processed into peptides, can associate with MHC class I or II of antigen-presenting cells (APCs) to stimulate different T cell responses. However, the efficiency of DNA vaccination needs to be improved for use in humans. Importantly, in vivo DNA delivery combined with electroporation (EP) has been used successfully in the field of veterinary oncology, resulting in high rates of response after electrochemotherapy. Here, we evaluate the safety, immunogenicity, and protective efficacy of a novel linear SARS-CoV-2 DNA vaccine candidate delivered by intramuscular injection followed by electroporation (Vet-ePorator™) in ferrets. The linear SARS-CoV-2 DNA vaccine candidate did not cause unexpected side effects. Additionally, the vaccine elicited neutralizing antibodies and T cell responses on day 42 post-immunization using a low dose of the linear DNA construct in a prime-boost regimen. Most importantly, vaccination significantly reduced shedding of infectious SARS-CoV-2 through oral and nasal secretions in a ferret model., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

DNA integrity is a key issue in gene therapy and genetic vaccine approaches based on plasmid DNA. In contrast to messenger RNA that requires a controlled cold chain for efficacy, DNA molecules are considered to be more stable. In this study, we challenged this concept by characterizing the immunological response induced by a plasmid DNA vaccine delivered using electroporation. As a model, we used COVID-eVax, a plasmid DNA-based vaccine that targets the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Increased nicked DNA was produced by using either an accelerated stability protocol or a lyophilization protocol. Surprisingly, the immune response induced in vivo was only minimally affected by the percentage of open circular DNA. This result suggests that plasmid DNA vaccines, such as COVID-eVax that have recently completed a phase I clinical trial, retain their efficacy upon storage at higher temperatures, and this feature may facilitate their use in low-/middle-income countries.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of the COVID-19 pandemic, has been shown to infect a wide range of animal species, especially mammals, and besides human-to-human transmission, human-to-animal transmission has also been observed in some wild animals and pets, especially in cats. It has been demonstrated that cats are permissive to COVID-19 and are susceptible to airborne infections. Given the high transmissibility potential of SARS-CoV-2 to different host species and the close contact between humans and animals, it is crucial to find mechanisms to prevent the transmission chain and reduce the risk of spillover to susceptible species. Here, we show results from a clinical trial conducted in domestic cats to assess safety and immunogenicity of a linear DNA (linDNA) vaccine encoding the receptor-binding domain (RBD) from SARS-CoV-2 (Lin-COVID-eVax). Lin-COVID-eVax proved to be safe, with no significant adverse events, and was able to elicit both RBD-specific antibodies and T cells. Also, the linDNA vaccine induced neutralizing antibody titers against ancestral SARS-CoV-2 virus and its variants. These findings demonstrate the safety and immunogenicity of a genetic vaccine against COVID-19 administered to cats and strongly support the development of vaccines for preventing viral spread in susceptible species, especially those in close contact with humans., Competing Interests: Evvivax, Takis, and NeoMatrix are currently developing proprietary nucleic-acid vaccines based on DNA-EGT. Applied DNA and LineaRx are commercializing LinearDNA, its proprietary, large-scale PCR-based manufacturing platform that allows for the large-scale production of specific DNA sequences for biotherapeutic applications. The company’s common stock is listed on NASDAQ under ticker symbol “APDN,” and its publicly traded warrants are listed on OTC under ticker symbol “APPDW.”, (© 2023 The Authors.)