Outcomes of Multiorgan Heart Transplant Between Donation After Circulatory Death and Brain Death.

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.

P.O.L.A.R. Star: A New Framework Developed and Applied by One Mid-Sized Pharmaceutical Company to Drive Digital Transformation in R&D.

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.

Ex vivo heart perfusion: an updated systematic review.

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.

Current Understanding and Future Directions of Transcatheter Devices to Assist Failing Fontan.

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.

Emerging Treatments Targeting the Tumor Microenvironment for Advanced Chondrosarcoma.

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.

Transcatheter prosthetic valve endocarditis of an aortic valve-in-valve bioprosthesis in an elderly male.

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.

Techniques and Technologies to Improve Vein Graft Patency in Coronary Surgery.

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.

Predictors of Survival After Heart Transplant in the New Allocation System: A UNOS Database Analysis.

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.

Optimizing Safety and Success: The Advantages of Bloodless Cardiac Surgery. A Systematic Review and Meta-Analysis of Outcomes in Jehovah's Witnesses.

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.

Surgical Ablation for Atrial Fibrillation During Mitral Valve Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

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, I2 = 55%), at 6-month follow-up (OR 7.21, 95% CI 4.30 to 12.11, I2 = 34%), and at 1-year follow-up (OR 8.41, 95% CI 5.14 to 13.77, I2 = 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, I2 = 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.

del Nido versus hematic cardioplegia in minimally invasive aortic valve surgery.

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.

Left ventricular assist device exchange: a review of indications, operative procedure, and outcomes.

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.

Increasing differential diagnosis between lipoma and liposarcoma through radiomics: a narrative review.

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.

Endoscopic aortic valve surgery in isolated and concomitant procedures.

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.

Nonischemic Donor Heart Preservation: New Milestone in Heart Transplantation History.

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.

Novel Sources of Biodiversity and Biomolecules from Bacteria Isolated from a High Middle Ages Soil Sample in Palermo (Sicily, Italy).

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.

Long-Term Outcomes and Risk Factors Analysis for Patients Undergoing Thoracic Endovascular Aorta Repair (TEVAR), According to the Aortic Pathologies.

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.

Venous External Support in Coronary Artery Bypass Surgery: A Systematic Review and Meta-Analysis.

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; I²â€¯= 0%). Intimal hyperplasia area [MD -0.77 mm2; 95%CI -1.10 to -0.45; I2 = 0%] and thickness [MD -0.06 mm; 95% CI -0.08 to -0.04; I2=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; I2 = 0%) and graft ectasia (OR 0.53; 95%CI 0.32-0.88; I2 = 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.