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There is insufficient data on the outcomes of donation after circulatory death (DCD) multiorgan transplant that includes heart. The primary objective of this study is to compare the overall survival outcomes of DCD and donation after brain death (DBD) multiorgan transplants. We identified all heart transplant patients from 2019 to June of 2023 using the United Network for Organ Sharing (UNOS) Database who also received an additional organ (kidney, liver, and lungs). A total of 1,844 DBD and 91 DCD multiorgan transplants occurred within the study period, the majority being combined heart-kidney transplantation. More patients were listed at a higher status in the DBD group (p < 0.05) and were in the intensive care unit (ICU) before transplant (p < 0.05). Despite the higher ischemia time in the DCD group (p < 0.05), the overall unmatched survival did not differ between the two groups (p < 0.05). Within the heart-kidney transplants, the overall survival between DBD and DCD heart-kidney transplants did not differ in either unmatched or matched groups (unmatched p = 0.5, matched p = 0.5). In conclusion, the data on the outcomes of DCD multiorgan transplants are limited. Still, our analysis of the currently available data suggests that the overall survival is comparable in the DCD multiorgan transplants., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Due to the discrepancy between patients awaiting a heart transplant and the availability of donor hearts, strategies to expand the donor pool and improve the transplant's success are crucial. This review aims to summarize current knowledge on the ex vivo heart preservation (EVHP) experience as an alternative to standard cold static storage (CSS). EVHP techniques can improve the preservation of the donor's heart before transplantation and allow for pre-transplant organ evaluation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Digital transformation has become a cornerstone of innovation in pharmaceutical research and development (R&D). Pharmaceutical companies now have an imperative to embrace transformation, including mid-sized and small-sized companies despite resource limitations that do not allow economies of scale compared with larger organizations. This article describes the journey undertaken by Chiesi to develop an efficient framework to drive digital transformation along its R&D value chain with the objective of building and refreshing a clear roadmap and relevant priorities, together with identifying and enabling new digital capabilities and skills within R&D, defining tools and processes that will guide Chiesi activities in the space up to mid-long term. This work has led so far to five main achievements, which align with the steps in the framework: a strategically aligned roadmap with key focus areas for digital transformation and a dedicated team to lead the effort; a common language for data across the R&D value chain; an internal mindset that's open to innovation and participation in key external networks and consortia; a set of quick-win use cases for the new framework; and a defined set of Key Performance Indicators (KPIs) and monitoring tools for digital transformation. The work presented here demonstrates that R&D digital transformation should represent an ongoing process to enable cross-functional collaboration and integration within complex corporate environments that face an ever-growing volume of diverse data, to efficiently support business needs, and to ensure a positive impact on patient care., (© 2024. The Author(s).)

Transcatheter aortic valve replacement (TAVR) is the percutaneous alternative to traditional surgery. Infective endocarditis is a fatal complication of TAVR, especially in the elderly. A 65-year-old male with a history of valve-in-valve TAVR presented to our emergency room with altered mentation. On examination, he was febrile. Laboratory investigations and echocardiography suggested infective endocarditis. Explantation and surgical aortic valve replacement were planned. The biopsy of the prostheses showed acute inflammation. Transcatheter prosthetic valve endocarditis warrants early diagnosis, particularly in the elderly. Our case emphasizes the importance of the prompt inclusion of endocarditis in the differential and surgical referral., Competing Interests: The authors have no conflict of interest.

Chondrosarcoma (ChS), a malignant cartilage-producing tumor, is the second most frequently diagnosed osseous sarcoma after osteosarcoma. It represents a very heterogeneous group of malignant chemo- and radiation-resistant neoplasms, accounting for approximately 20% of all bone sarcomas. The majority of ChS patients have a good prognosis after a complete surgical resection, as these tumors grow slowly and rarely metastasize. Conversely, patients with inoperable disease, due to the tumor location, size, or metastases, represent a great clinical challenge. Despite several genetic and epigenetic alterations that have been described in distinct ChS subtypes, very few therapeutic options are currently available for ChS patients. Therefore, new prognostic factors for tumor progression as well as new treatment options have to be explored, especially for patients with unresectable or metastatic disease. Recent studies have shown that a correlation between immune infiltrate composition, tumor aggressiveness, and survival does exist in ChS patients. In addition, the intra-tumor microvessel density has been proven to be associated with aggressive clinical behavior and a high metastatic potential in ChS. This review will provide an insight into the ChS microenvironment, since immunotherapy and antiangiogenic agents are emerging as interesting therapeutic options for ChS patients.

Even if the Fontan operation is the surgical treatment of choice in patients with univentricular physiology, it remains a palliative strategy. Consequently, when Fontan patients reach adulthood, the majority of them develop late clinical sequelae of a failing cavo-pulmonary circuit (eg, liver failure, protein-losing enteropathy, and arrhythmias). Although heart transplantation represents the gold standard to treat this condition, Fontan patients usually accede to this therapy late, when risk of mortality is significantly increased, and a shortage of donor hearts limits transplantation in this special population. Mechanical circulatory support is an emerging field, but it is still in the experimental stage. Current mechanical circulatory devices have been used in Fontan circulation but are associated with the need for high-risk redo surgery. Percutaneous pumps are an emerging field that is still under investigation, with multiple prototypes developed. This review aims to analyze the hemodynamic profile of the developed intravascular pumps and their application in the preclinical scenario in the Fontan circulation., (© 2024 The Author(s).)

Clinical predictors of posttransplant graft loss since the United Network for Organ Sharing (UNOS) heart allocation system change have not been well characterized. Single organ adult heart transplants from the UNOS database were identified (n = 10,252) and divided into a test cohort (n = 6,869, 67%) and validation cohort (n = 3,383, 33%). A Cox regression analysis was performed on the test cohort to identify recipient and donor risk factors for posttransplant graft loss. Based on the risk factors, a score (max 16) was developed to classify patients in the validation cohort into risk groups of low (≤1), mid (2-3), high (≥4) risk. Recipient factors of advanced age, Black race, recipient blood group O, diabetes, etiology of heart failure, renal dysfunction, elevated bilirubin, redo-transplantation, elevated pulmonary artery pressure, transplant with a durable ventricular assist device, or transplant on extracorporeal membrane oxygenation (ECMO) or ventilator were associated with more posttransplant graft loss. Donor factors of ischemic time and donor age were also associated with outcomes. One year graft survival for the low-, mid-, high-risk groups was 94%, 91%, and 85%, respectively. In conclusion, easily obtainable clinical characteristics at time of heart transplant can predict posttransplant outcomes in the current era., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Vein grafts are the most used conduits in coronary artery bypass grafting (CABG), even though many studies have suggested their lower patency compared to arterial alternatives. We have reviewed the techniques and technologies that have been investigated over the years with the aim of improving the quality of these conduits. We found that preoperative and postoperative optimal medical therapy and no-touch harvesting techniques have the strongest evidence for optimizing vein graft patency. On the other hand, the use of venous external support, endoscopic harvesting, vein preservation solution and anastomosis, and graft configuration need further investigation. We have also analyzed strategies to treat vein graft failure: when feasible, re-doing the CABG and native vessel primary coronary intervention (PCI) are the best options, followed by percutaneous procedures targeting the failed grafts.

Transfusions are extremely frequent after cardiac surgery, and they have a considerable economic burden and impact on outcomes. Optimal patient blood management could play a fundamental role in reducing the rate of transfusion and Jehovah's Witnesses (JW) represent the ideal surrogate study population. This meta-analysis compares outcomes of JWs and non-JWs' patients undergoing cardiac surgery, assessing the safety of a bloodless cardiac surgery. A scoping review was conducted using a search strategy for studies assessing outcomes of JW undergoing cardiac surgery. The primary outcome was perioperative mortality, and a random-effects meta-analysis was performed. Ten studies were included in our meta-analysis, involving 780 JW patients refusing any type of transfusion ("JW") and 1182 patients accepting transfusion if needed ("non-JW"). 86% of non-JW patients received at least 1 transfusion. There was no significant difference in terms of perioperative mortality (OR 0.91; 95% CI 0.55-1.52; p = 0.72). The volume blood loss was significantly less in the JW (p = 0.001), while the rate of reoperation for bleeding was also lower, but not statistically significative, in the JW (p = 0.16). Both preoperative and postoperative hemoglobin and hematocrit were significantly higher in the JW. Therefore, we concluded that bloodless cardiac surgery is safe and early outcomes are similar between JW and non-JW patients: optimal patient blood management is fundamental in guarantying these results. Further studies are needed to assess if a limitation of transfusion could have a positive long-term impact on outcomes., 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 Elsevier Inc. All rights reserved.)

Although surgical ablation has been shown to produce excellent outcomes at follow-up for patients with atrial fibrillation who underwent mitral valve replacement/repair (MVR), this procedure is not commonly performed. Our objective was to conduct a systematic review and meta-analysis to evaluate the outcomes of concomitant surgical ablation during MVR. Three databases were systematically reviewed for randomized clinical trials published by August 2022. The primary outcome was sinus rhythm (SR) at 12 months. Secondary outcomes included SR at discharge and 6 months, all-cause mortality, permanent pacemaker implantation, and stroke and thromboembolic events. A random-effects meta-analysis was performed, calculating odds ratios (ORs) for each outcome. Thirteen studies were included, involving 1,089 patients comparing patients who underwent either isolated MVR ("MVR-only") or concomitant surgical ablation during MVR ("MVR+Ablation"). The odds of SR were significantly higher in the MVR+Ablation group at discharge (OR 9.62, 95% confidence interval [CI] 4.87 to 19.02, I 2  = 55%), at 6-month follow-up (OR 7.21, 95% CI 4.30 to 12.11, I 2  = 34%), and at 1-year follow-up (OR 8.41, 95% CI 5.14 to 13.77, I 2  = 48%). All-cause mortality was not different in the groups, as were stroke and thromboembolic events, whereas the odds of permanent pacemaker implantation were slightly higher in the MVR+Ablation group (OR 1.87, 95% CI 1.11 to 3.17, I 2  = 0%). Concomitant surgical ablation during MVR showed excellent outcomes at short-term follow-up, despite a slightly higher rate of permanent pacemaker implantation. Further studies with longer follow-ups are needed to assess if the SR is maintained over the years., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The quality of a myocardial protection of a single-dose del Nido cardioplegia versus multiple dose blood-based cardioplegia on myocardial injury, outcomes and operative times in patients undergoing minimally invasive aortic valve replacement is basically unreported., Methods and Results: Preoperative and post-operative data, as well as technical details from isolated minimally invasive aortic valve replacements, performed using single-dose or multiple-dose cardioplegia were prospectively collected and retrospectively analysed. A total of 110 patients undergoing minimally invasive valve replacements at our institution composed two groups: 55 patients in the blood cardioplegia group (BloCa) and 55 in the del Nido group (DeNiCa). The two-matched groups were comparable in terms of preoperative variables. In the DeNiCa group, there was a statistically significant less need for cardiac defibrillation after aortic cross-clamp release ( p  < 0.001). Moreover, the BloCa group received intraoperatively more blood transfusions ( p  = 0.001) and more insulin administration for higher glucose levels ( p  < 0.001). The BloCa group showed higher intraoperative lactate levels ( p  = 0.01). Need for post-operative inotropic and vasoactive support, Creatine Kinase-MB levels after 6 and 12 h, onset of post-operative atrial fibrillation and length of stay were similar. No deaths occurred in neither groups., Conclusion: Single-dose del Nido cardioplegia in the setting of minimally invasive aortic surgery seems to offer adequate myocardial protection, comparable to multiple dose hematic cardioplegia. It has been documented a lower peri-operative need of defibrillation after cross-clamp release, lactate- and glucose peak values, as well as less blood transfusions compared to blood cardioplegic strategy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Thoracic endovascular aortic repair (TEVAR) has become a standard treatment for acute and chronic thoracic aorta diseases. We analyzed long-term outcomes and risk factors of TEVAR procedures according to the aortic pathology., Methods: Demographics, indications, technical details, and outcomes of patients undergoing TEVAR procedures in our institutions were prospectively collected and retrospectively analyzed. Overall survival was determined using Kaplan-Meier methods while log-rank tests were used to compare the survival between groups. Cox regression analysis was used to identify risk factors., Results: Between June 2002 and April 2020, 116 patients underwent TEVAR for different thoracic aorta diseases. Among them, 47 patients (41%) underwent TEVAR for aneurysmatic aortic disease, 26 (22%) for type-B aortic dissection, 23 (20%) for penetrating aortic ulcer, 11 (9%) after previous type-A dissection treatment, and 9 (8%) for traumatic aortic injury. Patients with posttraumatic aortic injury were younger (P < 0.01) with less hypertension (P < 0.01), diabetes (P < 0.01), and prior cardiac surgery (P < 0.01). Survival was different based on indication for TEVAR (log rank 0.024). Patients after previous type-A dissection treatment had the worst survival rate (50% at 5 years) while survival for aneurysmatic aortic disease was 55% at 5 years. No late death occurred in the traumatic group. Cox-regression model identified independent predictors for mortality: age (hazard ratio [HR]: 1.05, 95% confidence interval [CI]: 1.01-1.09, P = 0.006), male gender (HR: 3.2, 95% CI: 1.1-9.2, P = 0.028), moderate chronic obstructive pulmonary disease (HR: 2.1, 95% CI: 1.02-4.55, P = 0.043), previous cardiac surgery (HR: 2.1, 95% CI: 1.008-4.5, P = 0.048), and treatment indication for aneurysm (HR: 2.6, 95% CI: 1.2-5.2, P = 0.008)., Conclusions: TEVAR is a safe and effective procedure with excellent long-term results in case of traumatic aortic injury. The overall long-term survival is affected by aortic pathology, associated comorbidities, gender, and previous cardiac surgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Heart transplantation is considered the gold standard for the treatment of advanced end-stage heart failure. However, standard donors after brain death are decreasing, whereas patients on the heart transplant waitlist are constantly rising. The introduction of the ex vivo machine perfusion device has been a turning point; in fact, these systems are able to significantly reduce ischemic times and have a potential effect on ischemia-related damage reduction. From a clinical standpoint, these machines show emerging results in terms of heart donor pool expansion, making marginal donors and donor grafts after circulatory death suitable for donation. This article aims to review mechanisms and preclinical and clinical outcomes of currently available ex vivo perfusion systems, and to explore the future fields of application of these technologies., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.)

The use of left ventricular assist devices (LVADs) is intended to treat patients with end-stage heart failure. Owing to technological advances, these devices are becoming more durable. However, LVADs may need to be exchanged when complications arise and heart transplantation is not possible. Indications for LVAD exchange (LVADE) include device thrombosis, device infections, and pump component failure. LVADE has historically been associated with a high risk of morbidity and mortality. In this review, we discuss the indications of LVADE, the decisional and technical aspects during surgery, and outcomes., Competing Interests: Conflict of interestThe authors declare that there is no conflict of interest., (© Indian Association of Cardiovascular-Thoracic Surgeons 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Neointimal hyperplasia and lumen irregularities are major contributors to vein graft failure and the use of VEST (R) should prevent this. In this review, we aim to evaluate the angiographic outcomes of externally supported vein grafts. Medline, Embase and Cochrane Library were systematically reviewed for randomized clinical trials published by August 2022. The primary outcome was graft failure. Secondary outcomes included graft ectasia, intimal hyperplasia area and thickness, and graft nonuniformity. Odds ratios (OR) for dichotomous variables and mean difference (MD) for continuous variables with 95% confidence intervals (CI) were pooled using a fixed-effects model. Three randomized controlled trials with a total of 437 patients were included with follow-up ranging from 1 to 2 years. The odds of graft failure were similar in the 2 groups (OR 1.22; 95%CI 0.88-1.71; I² = 0%). Intimal hyperplasia area [MD -0.77 mm 2 ; 95%CI -1.10 to -0.45; I 2  = 0%] and thickness [MD -0.06 mm; 95% CI -0.08 to -0.04; I 2 =0%] were significantly lower in the VEST group. Fitzgibbon Patency Scale of II or III (representing angiographic conduit nonuniformity; OR 0.67; 95%CI 0.48-0.94; I 2  = 0%) and graft ectasia (OR 0.53; 95%CI 0.32-0.88; I 2  = 33%) were also significantly lower in the VEST group. At short-term follow-up, VEST does not seem to reduce the incidence of graft failure, although it is associated with attenuation of intimal hyperplasia and nonuniformity. Longer angiographic follow-up is warranted to determine whether these positive effects might translate into a positive effect in graft failure and in long-term clinical outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The urban plan of Palermo (Sicily, Italy) has evolved throughout Punic, Roman, Byzantine, Arab, and Norman ages until it stabilized within the borders that correspond to the current historic center. During the 2012 to 2013 excavation campaign, new remains of the Arab settlement, directly implanted above the structures of the Roman age, were found. The materials investigated in this study derived from the so-called Survey No 3, which consists of a rock cavity of subcylindrical shape covered with calcarenite blocks: it was probably used to dispose of garbage during the Arabic age and its content, derived from daily activities, included grape seeds, scales and bones of fish, small animal bones, and charcoals. Radiocarbon dating confirmed the medieval origin of this site. The composition of the bacterial community was characterized through a culture-dependent and a culture-independent approach. Culturable bacteria were isolated under aerobic and anaerobic conditions and the total bacterial community was characterized through metagenomic sequencing. Bacterial isolates were tested for the production of compounds with antibiotic activity: a Streptomyces strain, whose genome was sequenced, was of particular interest because of its inhibitory activity, which was due to the Type I polyketide aureothin. Moreover, all strains were tested for the production of secreted proteases, with those belonging to the genus Nocardioides having the most active enzymes. Finally, protocols commonly used for ancient DNA studies were applied to evaluate the antiquity of isolated bacterial strains. Altogether these results show how paleomicrobiology might represent an innovative and unexplored source of novel biodiversity and new biotechnological tools. IMPORTANCE One of the goals of paleomicrobiology is the characterization of the microbial community present in archaeological sites. These analyses can usually provide valuable information about past events, such as occurrence of human and animal infectious diseases, ancient human activities, and environmental changes. However, in this work, investigations about the composition of the bacterial community of an ancient soil sample (harvested in Palermo, Italy) were carried out aiming to screen ancient culturable strains with biotechnological potential, such as the ability to produce bioactive molecules and secreted hydrolytic enzymes. Besides showing the biotechnological relevance of paleomicrobiology, this work reports a case of germination of putatively ancient bacterial spores recovered from soil rather than extreme environments. Moreover, in the case of spore-forming species, these results raise questions about the accuracy of techniques usually applied to estimate antiquity of DNA, as they could lead to its underestimation., Competing Interests: The authors declare no conflict of interest.

Objectives: To evaluate early outcomes of endoscopic aortic valve replacement (AVR) and risks of concomitant procedures done through the same working port., Methods: At our institution, we performed a data analysis of 342 consecutive patients (from July 2013 to May 2021) who underwent endoscopic AVR with or without associated major procedure. Preoperative, intraoperative, postoperative data were evaluated. Subsequently, we perform a comparative analysis between the isolated and concomitant surgery group. The surgical access was a 3- to 4-cm working port in the second right intercostal space and 3 additional 5-mm mini-ports for the introduction of the thoracoscope, the transthoracic clamp and the vent line. Cardiopulmonary by-pass was achieved through peripheral cannulation., Results: 105 patients (30.7%) underwent combined procedure: 2 coronary artery bypass (1.9%), 21 ascending aorta replacement (19.6%), 41 mitral surgery (38.3%), 16 mitral and tricuspid surgery (15%) and 25 other procedure (27%). Death occurred in 1 patient (0.4%) in the isolated group versus 2 patients (1.9%) in the combined group (P = 0.175). Seven strokes were observed, 4 in isolated procedures (1.7%) and 3 in the concomitant ones (2.85%) (P = 0.481). Surgical revision for bleeding was performed always through the same access in 13 patients (5.4%) versus 11 patients (10.4%) (P = 0.096). Pacemaker implantation was necessary in 5 patients (2.1%) versus 8 patients (7.6%) (P = 0.014). Median intubation time was 5 (2) h vs 6 (8) (P < 0.080)., Conclusions: Through a single working port made for endoscopic AVR, a concomitant procedure may be done without affecting in-hospital mortality and postoperative stroke rate., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Soft tissue sarcomas (STSs) are rare, heterogeneous, and very often asymptomatic diseases. Their diagnosis is fundamental, as is the identification of the degree of malignancy, which may be high, medium, or low. The Italian Medical Oncology Association and European Society of Medical Oncology (ESMO) guidelines recommend magnetic resonance imaging (MRI) because the clinical examination is typically ineffective. The diagnosis of these rare diseases with artificial intelligence (AI) techniques presents reduced datasets and therefore less robust methods. However, the combination of AI techniques with radiomics may be a new angle in diagnosing rare diseases such as STSs. Results obtained are promising within the literature, not only for the performance but also for the explicability of the data. In fact, one can make tumor classification, site localization, and prediction of the risk of developing metastasis. Thanks to the synergy between computer scientists and radiologists, linking numerical features to radiological evidence with excellent performance could be a new step forward for the diagnosis of rare diseases., Competing Interests: The authors declare that they have no conflicts of interest., (© The Author(s) 2023.)

Minimally invasive cardiac surgery has increased in popularity to reduce the morbidity associated with open heart surgery. In this article, a totally endoscopic case series is presented in which anterior pericardiectomy is performed by peripheral femoral arterial and venous cannulation. Right periareoal incision and right submammary incision were used for male and female patients, respectively, to access the heart by the fourth intercostal space.

Objective: Το perform a systematic review with meta-analysis of published data comparing outcomes between a percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in dialysis-dependent patients., Methods: We searched PubMed, Scopus, and Cochrane databases for studies including dialysis-dependent patients who underwent either CABG or PCI. This meta-analysis follows the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We conducted one-stage and two-stage meta-analysis with Kaplan-Meier-derived individual patient data for overall survival and meta-analysis with the random-effects model for the in-hospital mortality and repeat revascularization., Results: Twelve studies met our eligibility criteria, including 13,651 and 28,493 patients were identified in the CABG and PCI arms, respectively. Patients who underwent CABG had overall improved survival compared with those who underwent PCI at the one-stage meta-analysis (hazard ratio [HR]: 1.12, 95% confidence interval [CI]: 1.09-1.16, p < .0001) and the two-stage meta-analysis (HR: 1.15, 95% CI: 1.08-1.23, p < .001, I 2  = 30.0%). Landmark analysis suggested that PCI offers better survival before the 8.5 months of follow-up (HR: 0.96, 95% CI: 0.92-0.99, p = .043), while CABG offers an advantage after this timepoint (HR: 1.3, 95% CI: 1.22-1.32, p < .001). CABG was associated with increased odds for in-hospital mortality (odds ratio [OR]: 1.70, 95% CI: 1.50-1.92, p < .001, I 2  = 0.0%) and decreased odds for repeat revascularization (OR: 0.22, 95% CI: 0.14-0.34, p < .001, I 2  = 58.08%)., Conclusions: In dialysis-dependent patients, CABG was associated with long-term survival but a higher risk for early mortality. The risk for repeat revascularization was higher with PCI., (© 2022 Wiley Periodicals LLC.)

Objectives: Transcatheter aortic valve replacement (TAVR) represents a valid treatment for patients with aortic valve stenosis and high or intermediate surgical risk. However, biological transcatheter valves can also experience a structural degeneration after years, and a redo-TAVR procedure (TAVR-in-TAVR) can be a valid option. We revised the current available literature for indications, procedural and technical details and outcome on TAVR-in-TAVR procedures for degenerated TAVR valves., Methods: A systematic search was conducted in the public medical database for scientific articles on TAVR-in-TAVR procedures for degenerated transcatheter valves. Data on demographics, indications, first and second transcatheter valve type and size, mortality, complications and follow-up were extracted and analysed., Results: A total of 13 studies (1 multicentre, 3 case series, 9 case reports) were included in this review, with a total amount of 160 patients treated with TAVR-in-TAVR procedures for transcatheter valve failure. The mean age was 74.8 ± 7.8 with 84 males (52.8%). The mean elapsed time from the first TAVR procedure was 58.1 ± 23.4 months. Main indication for TAVR-in-TAVR was pure stenosis (38.4%, with mean gradient of 44.5 ± 18.5 mmHg), regurgitation (31.4%), mixed stenosis and regurgitation (29.5%) and leaflet thrombosis (8.8%). Procedural success rate was 86.8%, with second TAVR valve malposition occurred in 4 cases (2.5%). The hospital mortality rate was 1.25% (2/160). Post-procedural echocardiographic control showed moderate regurgitation in 5.6% of patients (9/160) and residual transvalvular mean gradient ≥20 mmHg in 5% of cases. Postoperative complications included major vascular complications (8.7%), new pacemaker implantation (8.7%), acute kidney failure (3.7%), stroke (0.6%) and coronary obstruction (0.6%). The mean follow-up time was 6 ± 5.6 months with 1 non-cardiovascular death reported., Conclusions: TAVR-in-TAVR represents a valid alternative to standard surgery for the treatment of degenerated transcatheter valves in high-risk patients. Despite these promising results, further studies are required to assess durability and haemodynamic performances of the second TAVR valve., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Air emboli are reported to enter the cardiovascular system during cardiac surgery despite air-bubble filters in the arterial line of the cardiopulmonary bypass (CPB). A potential association with stroke, covert cerebral insults and cognitive decline after cardiac surgery has been hypothesized. Although most of the previous studies failed to prove it, this hypothesis cannot be rejected because the situation in the operating room (OR) is multifactorial and complex. Therefore, rigorous and standardized protocols are needed to investigate sources, patterns, as well as effective quantity and volume of air embolism.  We hereby present our protocol in detail for systematic data collection as a standard quality control measure at our center, where air bubbles in the cardiopulmonary bypass circuit are measured by a commercial bubble counter. We also show a preview of the type of information that can be obtained for future analysis. The eventual aim is to determine a potential association between air emboli and adverse postoperative outcomes, as well as to identify major sources of air bubbles generation and in the long run to find effective prevention strategies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Puthettu et al.)

Background: The optimal revascularization strategy for patients with left main coronary artery disease is still controversial. This is systematic review and meta-analysis aims to evaluate the outcomes of percutaneous coronary intervention (PCI) with drug-eluting stents compared with coronary artery bypass graft (CABG) for LM disease., Methods: Online electronic databases were systematically reviewed until January 2020 for randomized trials comparing PCI with drug-eluting stents and CABG. Primary outcomes were: all-cause mortality, myocardial infarction (MI), stroke, and repeated revascularization. Secondary outcomes included periprocedural and nonperiprocedural MI. The period of follow-up included 30 days, 1 year, and 5 years. Odds ratio and 95% confidence interval were calculated with a fixed-effects model., Results: A total of 4595 patients (5 randomized trials) with left main coronary artery disease were included. At 30 days and 1 year, PCI was associated with lower incidence of stroke, higher repeated revascularization, and similar odds of mortality and MI compared with CABG. At 5 years, PCI was associated with higher rates of MI (odds ratio, 1.43; 95% confidence interval, 1.13-1.79; P = .003) and repeat revascularization (odds ratio, 1.89; 95% CI, 1.58-2.26; P < .001) than CABG. PCI was associated with lower periprocedural MI at 30 days, whereas at 5 years PCI was associated with higher nonperiprocedural MI (odds ratio, 2.32; 95% confidence interval, 1.62-3.31; P < .001). Mortality and stroke rate did not differ at 5-year follow-up., Conclusions: Patients with left main coronary artery disease treated with either PCI or CABG do not show significant difference in early or 5-year mortality. Although CABG was associated with higher stroke rates at 30 days and 1 year, PCI was associated with an increase in MI and need for repeat revascularization at 5 years., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

In this paper, the recent progress on sinuous antennas is detailed, focusing the attention on the antenna geometry, dielectric structure, and miniaturization techniques. In the first part, we introduce the basic principles of the frequency-independent antenna, in particular the self-complementary and log-periodic geometries, as well as the antenna geometries, all characterized in terms of angles. The operating principles, main advantages, system design considerations, limits, and challenges of conventional sinuous antennas are illustrated. Second, we describe some technical solutions aimed to ensure the optimal trade-off between antenna size and radiation behavior. To this aim, some special modification of the antenna geometry based on the meandering as well as on the loading with dielectric structures are presented. Moreover, the cavity backing technique is explained in detail as a method to achieve unidirectional radiation. Third, we present a new class of supershaped sinuous antenna based on a suitable merge of the 2D superformula and the sinuous curve. The effect of the free parameters change on the antenna arm geometry as well as the performance improvement in terms of directivity, beam stability, beam angle, gain, and radiating efficiency are highlighted.

Background: There is a rising trend for transcatheter aortic valve implantation (TAVI) in bicuspid aortic stenosis patients. Data on the use of self-expandable (SEV) vs. balloon-expandable (BEV) valves in these patients are scarce. Therefore, we systematically compared clinical outcomes in bicuspid aortic stenosis patients treated with SEV and BEV., Methods: Data were extracted from PubMed/MEDLINE, EMBASE, CENTRAL/CCTR, ClinicalTrials.gov, SciELO, LILACS, Google Scholar and reference lists of relevant articles. Eight studies published from 2013 to 2020 including a total of 1,080 patients (BEV: n = 620; SEV: n = 460) were selected. Primary endpoints were procedural, 30-day and 1-year mortality. Secondary endpoints were new pacemaker implantation, annular rupture, coronary obstruction, moderate-to-severe paravalvular leak, need of second valve, stroke and acute kidney injury., Results: We found no statistically significant difference in mortality between patients treated with BEV vs. SEV during index procedure, at 30 days and at 1 year. BEVs showed a statistically significant higher risk of annulus rupture (2.5%) in comparison with SEV (0%) (OR 5.81 [95% CI, 3.78-8.92], p < .001). New generation BEVs were also associated with significantly less paravalvular leak when compared to new generation SEVs (OR 0.08 [95% CI, 0.02-0.35], p = .001)., Conclusions: This meta-analysis of observational studies of TAVI for bicuspid valves, showed no difference in short- and mid-term TAVI mortality with BEVs and SEVs. BEVs presented a higher risk of annular rupture in comparison with SEV., (© 2021 Wiley Periodicals LLC.)

We aimed to analyze the outcome and identify predictors of hospital mortality in patients with refractory cardiac arrest (CA) complicating acute coronary syndromes (ACS) and requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) treatment. Between Jan-2005 and Dec-2019, 51 patients underwent urgent VA-ECMO implantation for CA in ACS. Patients were divided in two groups: "in-hospital" cardiac arrest (IHCA) and "out-of-hospital" cardiac arrest (OHCA). Prospectively collected data were retrospectively analyzed and compared between groups. Predictors for hospital mortality were investigated. IHCA and OHCA patients were 32 (62.7%) and 19 (37.3%), respectively. The groups differed for: male gender (72% vs 95%; p = 0.070), lactate peak level (8.5 ± 4.3vs10.7 ± 2.9; p = 0.023), total elapsed time from CA to VA-ECMO implantation in both groups (p < 0.001) and elapsed time from CA (IHCA group) or hospital arrival (OHCA group) to VA-ECMO implantation (38 min vs 80 min; p = 0.001). At logistic regression analysis, concomitant lactate level greater than 8.0 mmol/L and elapsed time from CA to VA-ECMO ≥ 30 min were predictors of increased mortality (OR 3.9; 95% CI 1.19-12.79; p = 0.025) for the entire population. In-hospital mortality was 60.8% (31/51 patients): 68.4% in OHCA group and 56.2% in IHCA group. No risk factors related to 30-day mortality resulted significant at univariable analysis. When rapidly instituted, VA-ECMO improves survival in patients with refractory cardiac arrest allowing coronary syndrome treatment. The association of an elapsed time from CA to VA-ECMO implantation longer than 30 min and a preoperative lactate peak level over 8.0 mmol/L predict a poor outcome, independently from being IHCA or OHCA., (© 2021. The Japanese Society for Artificial Organs.)

The tumor microenvironment modulates cancer growth. Extracellular vesicles (EVs) have been identified as key mediators of intercellular communication, but their role in tumor growth is largely unexplored. Here, we demonstrate that EVs from sarcoma patients promote neoangiogenesis via a purinergic X receptor 4 (P2XR4) -dependent mechanism in vitro and in vivo. Using a proteomic approach, we analyzed the protein content of plasma EVs and identified critical activated pathways in human umbilical vein endothelial cells (HUVECs) and human progenitor hematopoietic cells (CD34+). We then showed that vessel formation was due to rapid mitochondrial activation, intracellular Ca 2+ mobilization, increased extracellular ATP, and trafficking of the lysosomal P2XR4 to the cell membrane, which is required for cell motility and formation of stable branching vascular networks. Cell membrane translocation of P2XR4 was induced by proteins and chemokines contained in EVs (e.g. Del-1 and SDF-1). Del-1 was found expressed in many EVs from sarcoma tumors and several tumor types. P2XR4 blockade reduced EVs-induced vessels in angioreactors, as well as intratumor vascularization in mouse xenografts. Together, these findings identify P2XR4 as a key mediator of EVs-induced tumor angiogenesis via a signaling mediated by mitochondria-lysosome-sensing response in endothelial cells, and indicate a novel target for therapeutic interventions., (© 2021. The Author(s).)

Introduction : Aortic and mitral bioprosthesis are the gold standard treatment to replace a pathological native valve. However, bioprostheses are prone to structural valve degeneration, resulting in limited long-term durability. During the past decade, the implantation of transcatheter stent-valves within degenerated aortic and mitral bioprostheses, (the so-called 'valve-in-valve' procedure), represents a valid alternative to redo surgery in patients with high-risk surgical profiles. Areas covered : We reviewed the clinical outcomes and the procedural details of transcatheter aortic and mitral valve-in-valve series according to current published literature and include a practical guide for valve sizing and stent-valve positioning and strategies to prevent complications. Expert opinion : In both aortic and mitral positions meticulous planning is fundamental in these procedures to avoid serious complications including patient prosthesis mismatch, coronary obstruction and left ventricular outflow tract obstruction.

Myxoid liposarcoma (MLPS) is the second most common subtype of liposarcoma and has tendency to metastasize to soft tissues. To date, the mechanisms of invasion and metastasis of MLPS remain unclear, and new therapeutic strategies that improve patients' outcomes are expected. In this study, we analyzed by immunohistochemistry the immune cellular components and microvessel density in tumor tissues from patients affected by MLPS. In order to evaluate the effects of primary human MLPS cells on macrophage polarization and, in turn, the ability of macrophages to influence invasiveness of MLPS cells, non-contact and 3D organotypic co-cultures were set up. High grade MLPS tissues were found heavily vascularized, exhibited a CD3, CD4, and CD8 positive T lymphocyte-poor phenotype and were massively infiltrated by CD163 positive M2-like macrophages. Conversely, low grade MLPS tissues were infiltrated by a discrete amount of CD3, CD4, and CD8 positive T lymphocytes and a scarce amount of CD163 positive macrophages. Kaplan-Meier analysis revealed a shorter Progression Free Survival in MLPS patients whose tumor tissues were highly vascularized and heavily infiltrated by CD163 positive macrophages, indicating a clear-cut link between M2-like macrophage abundance and poor prognosis in patients. Moreover, we documented that, in co-culture, soluble factors produced by primary human MLPS cells induce macrophage polarization toward an M2-like phenotype which, in turn, increases MLPS cell capability to spread into extracellular matrix and to cross endothelial monolayers. The identification of M2-like polarization factors secreted by MLPS cells may allow to develop novel targeted therapies counteracting MLPS progression.

Volume overload and fluid congestion are a fundamental issue in the assessment and management of patients with heart failure (HF). Recent studies have found that in acute decompensated heart failure (ADHF), right and left-sided pressures generally start to increase before any notable weight changes take place preceding an admission. ADHF may be a problem of volume redistribution among different vascular compartments instead of, or in addition to, fluid shift from the interstitial compartment. Thus, identifying heterogeneity of volume overload would allow guidance of tailored therapy. A comprehensive evaluation of congestive HF needs to take into account myriad parameters, including physical examination, echocardiographic values, and biomarker serum changes. Furthermore, potentially useful diagnostic tools include bioimpedance to measure intercompartmental fluid shifts, and evaluation of ultrasound lung comets to detect extravascular lung water., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate early results of valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) versus redo surgical aortic valve replacement (SAVR) for structural valve degeneration (SVD)., Background: ViV TAVR has been increasingly used for SVD, but it remains unknown whether it produces better or at least comparable results as redo SAVR., Methods: Observational studies comparing ViV TAVR and redo SAVR were identified in a systematic search of published research. Random-effects meta-analysis was performed, comparing clinical outcomes between the 2 groups., Results: Twelve publications including a total of 16,207 patients (ViV TAVR, n = 8,048; redo SAVR, n = 8,159) were included from studies published from 2015 to 2020. In the pooled analysis, ViV TAVR was associated with lower rates of 30-day mortality overall (odds ratio [OR]: 0.53; 95% confidence interval [CI]: 0.32 to 0.87; p = 0.017) and for matched populations (OR: 0.419; 95% CI: 0.278 to 0.632; p = 0.003), stroke (OR: 0.65; 95% CI: 0.55 to 0.76; p < 0.001), permanent pacemaker implantation (OR: 0.73; 95% CI: 0.22 to 2.43; p = 0.536), and major bleeding (OR: 0.49; 95% CI: 0.26 to 0.93; p = 0.034), as well as with shorter hospital stay (OR: -3.30; 95% CI: -4.52 to -2.08; p < 0.001). In contrast, ViV TAVR was associated with higher rates of myocardial infarction (OR: 1.50; 95% CI: 1.01 to 2.23; p = 0.045) and severe patient-prosthesis mismatch (OR: 4.63; 95% CI: 3.05 to 7.03; p < 0.001). The search revealed an important lack of comparative studies with long-term results., Conclusions: ViV TAVR is a valuable option in the treatment of patients with SVD because of its lower incidence of post-operative complications and better early survival compared with redo SAVR. However, ViV TAVR is associated with higher rates of myocardial infarction and severe patient-prosthesis mismatch., Competing Interests: Author Disclosures Dr. Pibarot has echocardiography Core Laboratory contracts with Edwards Lifesciences, for which he receives no direct compensation. Dr. Clavel has computed tomography Core Laboratory contract with Edwards Lifesciences, for which she receives no direct compensation and received research grant from Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although studies demonstrate its feasibility, there is ongoing debate on the short and long-term outcomes of MitraClip versus surgical repair or mitral valve replacement (MVR). The objective of this meta-analysis is to compare the safety, morbidity, mortality and long-term function following MitraClip compared to MVR., Methods: Articles were searched in PubMed and Cochrane databases for studies comparing outcomes of MitraClip and surgery on December 1, 2019. Eligible prospective, retrospective, randomized and non-randomized studies were reviewed., Results: A total of nine studies (n=1,873, MitraClip =533, MVR =644) were eligible for review. At baseline, MitraClip patients had more comorbidities than MVR patients, including myocardial infarction (P<0.001), chronic obstructive pulmonary disease (P=0.022) and chronic kidney disease (P<0.001). MitraClip was associated with shorter length of stay (-3.86 days; 95% CI, -4.73 to -2.99; P<0.01) with a similar safety profile. Residual moderate-to-severe mitral regurgitation was more frequent in MitraClip at discharge (OR, 2.81; 95% CI, 1.39-5.69; P<0.01) and at five years (OR, 2.46; 95% CI, 1.54-3.94; P<0.01), and there was a higher need for reoperation on the MitraClip group at latest follow-up (OR, 5.28; 95% CI, 3.43-8.11; P<0.01). The overall mortality was comparable between the two groups (HR, 2.06; 95% CI, 0.98-4.29; P=0.06) for a mean follow-up of 4.8 years., Conclusions: Compared to surgery, MitraClip demonstrates a similar safety profile and shorter length of stay in high-risk patients, at the expense of increased residual mitral regurgitation and higher reoperation rate. Despite this, long term mortality appears comparable between the two techniques, suggesting that a patient-tailored approach will lead to optimal results., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2021 Annals of Cardiothoracic Surgery. All rights reserved.)

During a minimally invasive implantation technique, the outflow graft of left ventricular assist device (LVAD) is tunnelled blindly through the pericardium or left pleura, with an inability to assess for twisting or malposition. Three-dimensional computed tomography scan (CT-scan) has a role in qualitative evaluation of the different outflow tract configurations. The different surgical minimally invasive approaches include: (a) mini-sternotomy and left mini-thoracotomy, (b) right mini-thoracotomy and left mini-thoracotomy, (c) subclavian artery access and left mini-thoracotomy. The outflow graft could be anastomosed to the left axillary artery or the ascending aorta. CT-scan reconstruction using syngo InSpace4D (Siemens, Muenchen, Germany) was used to provide fast segmentation and high-resolution images. The 3D reconstructions permit an evaluation of different anastomosis configurations and to assess the route of outflow graft., (© 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Objectives: In patients with reduced kidney function there are no established guidelines to suggest combined heart-kidney transplant (HKTx) versus sequential kidney transplant (SKTx) using preoperative value of estimated glomerular filtration (eGFR)., Methods: The United Network for Organ Sharing database was queried from 2000 to 2015 to evaluate survival of HKTx and SKTx population stratified by preoperative eGFR rate <45 mL/min. Aim of the study was to assess the eGFR rate that is most beneficial to perform a concomitant or a SKTx at time of transplant evaluation., Results: In our analysis, patients who required SKTx are recipients that, after heart transplantation, developed or worsened kidney insufficiency due to calcineurin inhibitor nephrotoxicity. In recipients with eGFR <30 or dialysis, a total of 545 received HKTx and 80 received SKTx. The median waiting time between heart and kidney transplant in SKTx group was 6 years. The overall post-transplant survival was 81% and 80% and 75% and 59% at 5 and 1 years for the HKTx and SKTx groups, respectively (P = .04). In recipients with eGFR from 30 to 44, a total of 107 received HKTx and 112 received SKTx. The median waiting time between heart and kidney transplant in SKTx group was 4 years. Overall post-transplant survival showed no statistically significant differences in HKTx group (n=107) compared with SKTx group (n=112) and was 90% and 95% at 1 year and 74% and 52% at 5 years, respectively (P = .4) ., Conclusions: To optimize organ and patient survival, eGFR value can be utilized to discern between HKTx versus SKTx in patients with decreased renal function at the time of heart transplantation. Patients with eGFR<30 or in dialysis presented better survival with HKTx, while both SKTx and HKTx are suitable for patients with eGFR between 30 and 45., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Silver nanoparticles (Ag-NPs) can be considered as a cost-effective alternative to antibiotics. In the presence of Fe(III)-citrate and Ag + , Klebsiella oxytoca DSM 29614 produces biogenic Ag-NPs embedded in its peculiar exopolysaccharide (EPS). K. oxytoca DSM 29614 was cultivated in a defined growth medium-containing citrate (as sole carbon source) and supplemented with Ag + and either low or high Fe(III) concentration. As inferred from elemental analysis, transmission and scanning electron microscopy, Fourier transform infrared spectrometry and dynamic light scattering, Ag-EPS NPs were produced in both conditions and contained also Fe. The production yield of high-Fe/Ag-EPS NPs was 12 times higher than the production yield of low-Fe/Ag-EPS NPs, confirming the stimulatory effect of iron. However, relative Ag content and Ag + ion release were higher in low-Fe/Ag-EPS NPs than in high-Fe/Ag-EPS NPs, as revealed by emission-excitation spectra by luminescent spectrometry using a novel ad hoc established phycoerythrin fluorescence-based assay. Interestingly, high and low-Fe/Ag-EPS NPs showed different and growth medium-dependent minimal inhibitory concentrations against Staphylococcus aureus ATCC 29213 and Pseudomonas aeruginosa ATCC 15442. In addition, low-Fe/Ag-EPS NPs exert inhibition of staphylococcal and pseudomonal biofilm formation, while high-Fe/Ag-EPS NPs inhibits staphylococcal biofilm formation only. Altogether, these results, highlighting the different capability of Ag + release, support the idea that Fe/Ag-EPS NPs produced by K. oxytoca DSM 29614 can be considered as promising candidates in the development of specific antibacterial and anti-biofilm agents.Key points • Klebsiella oxytoca DSM 29614 produces bimetal nanoparticles containing Fe and Ag.• Fe concentration in growth medium affects nanoparticle yield and composition.• Phycoerythrin fluorescence-based assay was developed to determine Ag + release.• Antimicrobial efficacy of bimetal nanoparticle parallels Ag + ions release.

Truffles are highly valuable ectomycorrhizal fungi that grow naturally in alkaline, calcareous soils. Iron deficiency chlorosis is a common problem in truffle (Tuber spp.) cultivation due to the high quantity of lime added to increase the pH of acidic soils. In this work, the effects of ferric hydroxide nanoparticles embedded in an exopolysaccharide (Fe-EPS NPs), extracted from cultures of Klebsiella oxytoca DSM 29614, were investigated on Quercus robur seedlings under greenhouse conditions. The plants were inoculated with Tuber borchii (the bianchetto truffle) and were cultivated with and without iron nanoparticle additions and compared with non-inoculated control plants. The seedlings were grown in limed soil in order to induce iron deficiency. Low doses of Fe-EPS NPs had a beneficial effect on the growth of the plants inoculated with T. borchii, increasing their height and reducing their leaf chlorosis 5 months after the first Fe-EPS NP treatment. Moreover, Fe-EPS NP treatments significantly increased the level of T. borchii mycorrhizal colonization and the ectomycorrhizal mantle thickness. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) applied to cross sections of mycorrhizas showed that Fe accumulated in the fungal mantle and apparently was slowly released serving as a resilient reservoir of iron for the plant. The results suggest that the application of Fe-EPS NPs is a promising technique in the production of Tuber mycorrhized plants in the nursery and could have future applications in the field.

Chondrosarcomas (CHS) are malignant cartilaginous neoplasms with diverse morphological features, characterized by resistance to chemo- and radiation therapies. In this study, we investigated the role of tumor-associated macrophages (TAM)s in tumor tissues from CHS patients by immunohistochemistry. Three-dimensional organotypic co-cultures were set up in order to evaluate the contribution of primary human CHS cells in driving an M2-like phenotype in monocyte-derived primary macrophages, and the capability of macrophages to promote growth and/or invasiveness of CHS cells. Finally, with an in vivo model of primary CHS cells engrafted in nude mice, we tested the ability of a potent peptide inhibitor of cell migration (Ac-d-Tyr-d-Arg-Aib-d-Arg-NH 2 , denoted RI-3) to reduce recruitment and infiltration of monocytes into CHS neoplastic lesions. We found a significant correlation between alternatively activated M2 macrophages and intratumor microvessel density in both conventional and dedifferentiated CHS human tissues, suggesting a link between TAM abundance and vascularization in CHS. In 3D and non-contact cu-culture models, soluble factors produced by CHS induced a M2-like phenotype in macrophages that, in turn, increased motility, invasion and matrix spreading of CHS cells. Finally, we present evidence that RI-3 successfully prevent both recruitment and infiltration of monocytes into CHS tissues, in nude mice.

Background: Reoperative coronary artery bypass grafting (redo-CABG) has declined during the last decade, while use of percutaneous coronary intervention (PCI) has increased. The aim of this retrospective study was to evaluate risk factors, in-hospital mortality, and long-term survival between first-time CABG and redo-CABG., Methods: From January 2009 to December 2015, 2,581 patients underwent first-time CABG procedures while 132 underwent isolated redo-CABG. Logistic regression was used to identify risk factors predictive of redo-CABG and after propensity matching the in-hospital morbidity and long-term all-cause mortality were compared., Results: Risk factors for redo-CABG were prior PCI, dyslipidaemia, diabetes and hypertension. After propensity matching there were no significant differences between the redo-CABG (n = 126) and first-time CABG groups (n = 232) in baseline characteristics. The adjusted in-hospital mortality was 3.1% for redo-CABG and 2.1% for first-time CABG (p = 0.55). Redo-CABG required significantly more intraoperative red blood cells (p = 0.03), platelets (p < 0.001), cryoprecipitate (p < 0.007) and fresh frozen plasma (p < 0.001) than first-time CABG. There was no significant difference in reoperation for bleeding (p = 0.72), prolonged ventilation (p = 0.98), postoperative stroke (p = 0.92) or dialysis (p = 0.44). The survival at 1, 3 and 5 years for redo-CABG was 93.5%, 90%, and 85% respectively, and 95.5%, 94.5%, 93% for first-time CABG, respectively (p = 0.2)., Conclusions: Prior PCI after first time CABG and the risk factors for atherosclerotic disease are predictive for redo-CABG. An increased use of blood products is required during redo-CABG. After propensity matching, in-hospital mortality and long-term survival for redo-CABG is comparable to first-time operation. Re-sternotomy does not impact the survival in redo-CABG., (Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Three-dimensional (3D)-printing technologies in cardiovascular surgery have provided a new way to tailor surgical and percutaneous treatments. Digital information from standard cardiac imaging is integrated into physical 3D models for an accurate spatial visualization of anatomical details. We reviewed the available literature and analysed the different printing technologies, the required procedural steps for 3D prototyping, the used cardiac imaging, the available materials and the clinical implications. We have highlighted different materials used to replicate aortic and mitral valves, vessels and myocardial properties. 3D printing allows a heuristic approach to investigate complex cardiovascular diseases, and it is a unique patient-specific technology providing enhanced understanding and tactile representation of cardiovascular anatomies for the procedural planning and decision-making process. 3D printing may also be used for medical education and surgical/transcatheter training. Communication between doctors and patients can also benefit from 3D models by improving the patient understanding of pathologies. Furthermore, medical device development and testing can be performed with rapid 3D prototyping. Additionally, widespread application of 3D printing in the cardiovascular field combined with tissue engineering will pave the way to 3D-bioprinted tissues for regenerative medicinal applications and 3D-printed organs., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Selection of cancer patients for treatment with immune checkpoint inhibitors remains a challenge due to tumour heterogeneity and variable biomarker detection. PD-L1 expression in 24 surgical chordoma specimen was determined immunohistochemically with antibodies 28-8 and E1L3N. The ability of patient-derived organoids to detect treatment effects of nivolumab was explored by quantitative and qualitative immunofluorescence and FACS analysis. The more sensitive antibody, E1L3N (ROC = 0.896, p = 0.001), was associated with greater tumour diameters (p = 0.014) and detected both tumour cells and infiltrating lymphocytes in 54% of patients, but only 1-15% of their cells. Organoids generated from PD-L1-positive patients contained both tumour cells and PD-1/CD8-positive lymphocytes and responded to nivolumab treatment with marked dose-dependent diameter reductions of up to 50% and increased cell death in both PD-L1-positive and negative organoids. Patient-derived organoids may be valuable to predict individual responses to immunotherapy even in patients with low or no immunohistochemical PD-L1 expression.

: In recent years, three-dimensional modelling and printing techniques have improved diagnosis and preprocedural planning during percutaneous interventions or surgery in cardiovascular disease. The raw data for the whole process are obtained through medical imaging, where regions of interest, that is heart chambers, valves, aorta, coronary vessels etc., are segmented and converted into three-dimensional digital models, which are then reproduced in physical replica by a three-dimensional printer. In the current article, a freeware patient-specific three-dimensional modelling and printing step-by-step procedure for preprocedural planning for complex heart diseases is presented and applied on four patients. Finally, a general discussion on the potential and future developments of personalized three-dimensional modelling and rapid prototyping for preprocedural planning is also presented.

Hemorrhagic or thrombotic events are common complications in heart failure patients with continuous-flow left ventricular assist device (CF-LVAD) support. Aim of this study is to investigate the effect of change in antiplatelet therapy after thrombotic or hemorrhagic events in patients with CF-LVAD support. A total of 231 CF-LVAD patients were included in this study. Patients with CF-LVAD were categorized into three groups: (1) high antiplatelet regimen as control group (aspirin [ASA] 325 mg; n = 115), (2) low antiplatelet regimen (ASA 81 mg; n = 82), started after hemorrhagic complications, and (3) double antiplatelet therapy (ASA/clopidogrel; n = 34) started after thrombotic complications. In our analysis, indications for low antiplatelet therapy were gastrointestinal (GI) bleeding (36%), hemorrhagic stroke (8%), and epistaxis (9%). Freedom from major bleeding events after changing therapy was comparable at 1 year for all three groups respectively 96%, 97%, and 91% (log rank = 0.421). Major indications for double antiplatelet therapy were pump thrombosis (15%) and coronary artery stent placement (2.5%). Freedom from thrombotic events after changing therapy was comparable at 1 year for groups 1, 2, and 3, respectively, 97%, 98%, and 91% (log rank = 0.317). Logistic regression shows that Heartmate II patients required more antiplatelet therapy changes compared with HeartWare (odds ratio [OR]: 3.611, 95% confidence interval [CI]: 1.8-6.9; p = 0.0001). HeartMate II required more adjustment of antiplatelet therapy during follow-up. Reducing or increasing antithrombotic therapies in response to major thrombotic hemorrhagic events in CF-LVAD patients is a safe strategy to avoid recurrences.

Heart transplantation is still the best treatment for patients with end-stage heart failure unresponsive to medical therapy or those treated with mechanical circulatory support. The surgical technique for heart transplantation is fraught with potential complications. One of these potential complications, kinking of the pulmonary artery after anastomosis of the recipient and donor pulmonary arteries, has been reported as a cause of acute right ventricular failure. We describe a technique to ensure proper configuration of the pulmonary artery after heart transplantation via a pulmonary arteriopexy to restore a physiologically appropriate angle of the great vessels., (© 2019 Wiley Periodicals, Inc.)