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.

Percutaneous coronary intervention versus coronary artery bypass graft surgery in dialysis-dependent patients: A pooled meta-analysis of reconstructed time-to-event data.

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, I2 = 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, I2 = 0.0%) and decreased odds for repeat revascularization (OR: 0.22, 95% CI: 0.14-0.34, p < .001, I2 = 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.

Balloon versus self-expandable transcatheter aortic valve implantation for bicuspid aortic valve stenosis: A meta-analysis of observational studies.

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.

Early predictors of mortality in refractory cardiogenic shock following acute coronary syndrome treated with extracorporeal membrane oxygenator.

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.

Sinuous Antenna for UWB Radar Applications.

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.

Combined Heart-Kidney Transplant Versus Sequential Kidney Transplant in Heart Transplant Recipients.

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.

Biogenic iron-silver nanoparticles inhibit bacterial biofilm formation due to Ag+ release as determined by a novel phycoerythrin-based assay.

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.

How to evaluate the outflow tract of LVAD after minimally invasive implantation by 3D CT-scan.

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.

Effects of biogenerated ferric hydroxides nanoparticles on truffle mycorrhized plants.

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.

Risk Factors and Outcomes in Redo Coronary Artery Bypass Grafting.

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.

Patient-derived organoids as a potential model to predict response to PD-1/PD-L1 checkpoint inhibitors.

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.

Myocardial protection with complementary dose of modified Del Nido cardioplegia during heart transplantation.

Myocardial protection during heart transplantation is achieved by a first dose of heart preservation solution during donor heart harvesting, while there is no consensus about the management of complementary doses during implantation in the recipient. We describe a preliminary case series where modified Del Nido Cardioplegia was used as complementary dose at the time of donor heart implantation.

Pulmonary arteriopexy to prevent pulmonary artery kinking in orthotopic heart transplantation.

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.

Changing demographics of heart donors: The impact of donor drug intoxication on posttransplant survival.

Recent reports have shown an increase in the number of organ donors from drug intoxication. The impact of donor drug use on survival after cardiac transplant remains unclear. The aim of our study was to illustrate changes in donor death mechanisms and assess the impact on posttransplant survival. We queried United Network of Organ Sharing thoracic transplant and deceased donor databases to identify patients undergoing heart transplantation between 2005 and 2015. We evaluated annual trends in donor death mechanisms. Recipients were propensity matched (drug-intoxicated-non-drug-intoxicated = 1:2) and posttransplant survival was compared using Kaplan-Meier curves. In total, 19 384 donor hearts were used for transplant during the period (donor age 31.6 ± 11.8 years, 72% male). Use of drug-intoxicated donors increased from 2% (2005) to 13% (2015) and decreased from blunt injury (40%-30%) and intracranial hemorrhage (29%-25%). After propensity matching, posttransplant survival of drug-intoxicated donor hearts was 90%, 82%, and 76% at 1, 3, and 5 years, which was similar to non-drug-intoxicated. Heart transplants using drug-intoxicated donors have significantly increased; however, they have not adversely affected posttransplant survival. Hearts from drug-intoxicated donors should be carefully evaluated and considered for transplant.

Genomic traits of Klebsiella oxytoca DSM 29614, an uncommon metal-nanoparticle producer strain isolated from acid mine drainages.

BACKGROUND: Klebsiella oxytoca DSM 29614 - isolated from acid mine drainages - grows anaerobically using Fe(III)-citrate as sole carbon and energy source, unlike other enterobacteria and K. oxytoca clinical isolates. The DSM 29614 strain is multi metal resistant and produces metal nanoparticles that are embedded in its very peculiar capsular exopolysaccharide. These metal nanoparticles were effective as antimicrobial and anticancer compounds, chemical catalysts and nano-fertilizers. RESULTS: The DSM 29614 strain genome was sequenced and analysed by a combination of in silico procedures. Comparative genomics, performed between 85 K. oxytoca representatives and K. oxytoca DSM 29614, revealed that this bacterial group has an open pangenome, characterized by a very small core genome (1009 genes, about 2%), a high fraction of unique (43,808 genes, about 87%) and accessory genes (5559 genes, about 11%). Proteins belonging to COG categories "Carbohydrate transport and metabolism" (G), "Amino acid transport and metabolism" (E), "Coenzyme transport and metabolism" (H), "Inorganic ion transport and metabolism" (P), and "membrane biogenesis-related proteins" (M) are particularly abundant in the predicted proteome of DSM 29614 strain. The results of a protein functional enrichment analysis - based on a previous proteomic analysis - revealed metabolic optimization during Fe(III)-citrate anaerobic utilization. In this growth condition, the observed high levels of Fe(II) may be due to different flavin metal reductases and siderophores as inferred form genome analysis. The presence of genes responsible for the synthesis of exopolysaccharide and for the tolerance to heavy metals was highlighted too. The inferred genomic insights were confirmed by a set of phenotypic tests showing specific metabolic capability in terms of i) Fe2+ and exopolysaccharide production and ii) phosphatase activity involved in precipitation of metal ion-phosphate salts. CONCLUSION: The K. oxytoca DSM 29614 unique capabilities of using Fe(III)-citrate as sole carbon and energy source in anaerobiosis and tolerating diverse metals coincides with the presence at the genomic level of specific genes that can support i) energy metabolism optimization, ii) cell protection by the biosynthesis of a peculiar exopolysaccharide armour entrapping metal ions and iii) general and metal-specific detoxifying activities by different proteins and metabolites.

Bacteria-produced ferric exopolysaccharide nanoparticles as iron delivery system for truffles (Tuber borchii).

Iron exopolysaccharide nanoparticles were biogenerated during ferric citrate fermentation by Klebsiella oxytoca DSM 29614. Before investigating their effects on Tuber borchii ("bianchetto" truffle) mycelium growth and morphology, they were tested on human K562 cell line and Lentinula edodes pure culture and shown to be non-toxic. Using these nanoparticles as iron supplement, the truffles showed extremely efficient iron uptake of over 300 times that of a commercial product. This avoided morphological changes in T. borchii due to lack of iron during growth and, with optimum nanoparticle dosage, increased growth without cell wall disruption or alteration of protoplasmatic hyphal content, the nuclei, mitochondria, and rough endoplasmic reticula being preserved. No significant modifications in gene expression were observed. These advantages derive from the completely different mechanism of iron delivery to mycelia compared to commercial iron supplements. The present data, in fact, show the nanoparticles attached to the cell wall, then penetrating it non-destructively without damage to cell membrane, mitochondria, chromatin, or ribosome. Low dosage significantly improved mycelium growth, without affecting hyphal morphology. Increases in hyphal diameter and septal distance indicated a healthier state of the mycelia compared to those grown in the absence of iron or with a commercial iron supplement. These positive effects were confirmed by measuring fungal biomass as mycelium dry weight, total protein, and ergosterol content. This "green" method for biogenerating iron exopolysaccharide nanoparticles offers many advantages, including significant economic savings, without toxic effects on the ectomycorrhizal fungus, opening the possibility of using them as iron supplements in truffle plantations.

Sarcoma Spheroids and Organoids-Promising Tools in the Era of Personalized Medicine.

Cancer treatment is rapidly evolving toward personalized medicine, which takes into account the individual molecular and genetic variability of tumors. Sophisticated new in vitro disease models, such as three-dimensional cell cultures, may provide a tool for genetic, epigenetic, biomedical, and pharmacological research, and help determine the most promising individual treatment. Sarcomas, malignant neoplasms originating from mesenchymal cells, may have a multitude of genomic aberrations that give rise to more than 70 different histopathological subtypes. Their low incidence and high level of histopathological heterogeneity have greatly limited progress in their treatment, and trials of clinical sarcoma are less frequent than trials of other carcinomas. The main advantage of 3D cultures from tumor cells or biopsy is that they provide patient-specific models of solid tumors, and they overcome some limitations of traditional 2D monolayer cultures by reflecting cell heterogeneity, native histologic architectures, and cell-extracellular matrix interactions. Recent advances promise that these models can help bridge the gap between preclinical and clinical research by providing a relevant in vitro model of human cancer useful for drug testing and studying metastatic and dormancy mechanisms. However, additional improvements of 3D models are expected in the future, specifically the inclusion of tumor vasculature and the immune system, to enhance their full ability to capture the biological features of native tumors in high-throughput screening. Here, we summarize recent advances and future perspectives of spheroid and organoid in vitro models of rare sarcomas that can be used to investigate individual molecular biology and predict clinical responses. We also highlight how spheroid and organoid culture models could facilitate the personalization of sarcoma treatment, provide specific clinical scenarios, and discuss the relative strengths and limitations of these models.

Leaflet Hypomobility After Transcatheter Aortic Valve Replacement: Thrombosis or Mechanical Factors? A Possible Pathophysiological Pattern.

Transcatheter heart valve replacement is an emerging technology in the treatment of valvular disease. During recent years, the opportunity to replace a heart valve via percutaneous access or via a miniinvasive access without the use of cardiopulmonary bypass has revolutionized the approach to this pathology. The different designs of transcatheter valves have also altered the spectrum of possible complications, with the unexpected occurrence of leaflet hypomobility after valve deployment. Here, the pathophysiological pattern of this complication is categorized, and an analysis provided of recently reported clinical evidences.

Perioperative statin therapy in cardiac surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: Several studies suggest beneficial effects of perioperative statin therapy on postoperative outcome after cardiac surgery. However, recent randomized controlled trials (RCTs) show potential detrimental effects. The objective of this systematic review is to examine the association between perioperative statin therapy and clinical outcomes in cardiac surgery patients. METHODS: Electronic databases were searched up to 1 November 2016 for RCTs of preoperative statin therapy versus placebo or no treatment in adult cardiac surgery. Postoperative outcomes were acute kidney injury, atrial fibrillation, myocardial infarction, stroke, infections, and mortality. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using fixed-effects meta-analyses. Primary analysis was restricted to trials with low risk of bias according to Cochrane methodology, and sensitivity analyses examined whether the risk of bias of included studies was associated with different results. We performed trial sequential analysis (TSA) to test the strength of the results. RESULTS: We included data from 23 RCTs involving 5102 patients. Meta-analysis of trials with low risk of bias showed that statin therapy was associated with an increase in acute kidney injury (314 of 1318 (23.82%) with statins versus 262 of 1319 (19.86%) with placebo; OR 1.26 (95%CI 1.05 to 1.52); p = 0.01); these results were supported by TSA. No difference in postoperative atrial fibrillation, myocardial infarction, stroke, infections, or mortality was present. On sensitivity analysis, statin therapy was associated with a slight increase in hospital mortality. Meta-analysis including also trials with high or unclear risk of bias showed no beneficial effects of statin therapy on any postoperative outcomes. CONCLUSIONS: There is no evidence that statin therapy in the days prior to cardiac surgery is beneficial for patients' outcomes. Particularly, statins are not protective against postoperative atrial fibrillation, myocardial infarction, stroke, or infections. Statins are associated with a possible increased risk of acute kidney injury and a detrimental effect on hospital survival could not be excluded. Future RCTs should further evaluate the safety profile of this therapy in relation to patients' outcomes and assess the more appropriate time point for discontinuation of statins before cardiac surgery.