Minimally Invasive Isolated and Hybrid Surgical Revascularization for Multivessel Coronary Disease: A Single-Center Long-Term Follow-Up.

INTRODUCTION: Some evidence suggests that surgical minimally invasive (MIDCAB) and hybrid coronary revascularization (HCR) are safe and potentially effective at short-term follow-up. Data on long-term outcomes are more limited and inconclusive. METHODS: Between February 2013 and December 2023, a total of 1997 patients underwent surgical coronary artery revascularization at our institution, of whom, 92 (4.7%) received left anterior mini-thoracotomy access (MIDCAB), either isolated (N = 78) or in combination with percutaneous coronary intervention (N = 14, HCR group). RESULTS: After a median follow-up of 75 months (range 3.1: 149 months), cardiac mortality was 0% while overall mortality was 3%, with one in-hospital mortality and two additional late deaths. Conversion to sternotomy happened in two patients (2.1%), and surgical re-explorations occurred in five patients (4.6%), of whom three for bleeding and two for graft failure. All patients received left internal mammary (LIMA) to left anterior descending artery (LAD) grafting (100%). In the HCR group, 10 patients (72%) showed percutaneous revascularization (PCI) after MIDCAB, showing PCI on a mean of 1.6 ± 0.6 vessels and implanting 2.1 ± 0.9 drug-eluting stents. CONCLUSIONS: MIDCAB, in isolation or in association with hybrid coronary revascularization, is associated with encouraging short- and long-term results in selected patients discussed within a dedicated heart-team.

Correction: Mazzini et al. Anatomical and Functional Outcomes after Endoresection and Adjuvant Ruthenium Brachytherapy for Uveal Melanoma: A Single-Center Experience. Life 2023, 13, 902.

There was an error in the original publication [...].

Acute Response of the Noninfarcted Myocardium and Surrounding Tissue Assessed by T2 Mapping After STEMI.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is associated with a systemic and local inflammatory response with edema. However, their role at the tissue level is poorly characterized. OBJECTIVES: This study aims to characterize T2 values of the noninfarcted myocardium (NIM) and surrounding tissue and to investigate prognostic relevance of higher NIM T2 values after STEMI. METHODS: A total of 171 consecutive patients with STEMI without prior cardiovascular events who underwent cardiac magnetic resonance after primary percutaneous coronary intervention were analyzed in terms of standard infarct characteristics. Edema of the NIM, liver, spleen, and pectoralis muscle was assessed based on T2 mapping. Follow-up was available for 130 patients. The primary endpoint was major adverse cardiac events (MACE), defined as cardiovascular death, myocardial infarction, unplanned coronary revascularization or rehospitalization for heart failure. The median time from primary percutaneous coronary intervention to cardiac magnetic resonance was 3 days (IQR: 2-5 days). RESULTS: Higher (above the median value of 45 ms) T2 values in the NIM area were associated with larger infarct size, microvascular obstruction, and left ventricular dysfunction and did not correlate with C-reactive protein, white blood cells, or T2 values of the pectoralis muscle, liver, and spleen. At a median follow-up of 17 months, patients with higher (>45 ms) NIM T2 values had increased risk of MACE (P < 0.001) compared with subjects with NIM T2 values ≤45 ms, mainly caused by a higher rate of myocardial reinfarction (26.3% vs 1.4%; P < 0.001). At multivariable analysis, higher NIM T2 values independently predicted MACE (HR: 2.824 [95% CI: 1.254-6.361]; P = 0.012). CONCLUSIONS: Higher NIM T2 values after STEMI are independently associated with worse cardiovascular outcomes, mainly because of higher risk of myocardial infarction.

Nature-based solutions can help reduce the impact of natural hazards: A global analysis of NBS case studies.

The knowledge derived from successful case studies can act as a driver for the implementation and upscaling of nature-based solutions (NBS). This work reviewed 547 case studies to gain an overview of NBS practices and their role in reducing the adverse impact of natural hazards and climate change. The majority (60 %) of case studies are situated in Europe compared with the rest of the world where they are poorly represented. Of 547 case studies, 33 % were green solutions followed by hybrid (31 %), mixed (27 %), and blue (10 %) approaches. Approximately half (48 %) of these NBS interventions were implemented in urban (24 %), and river and lake (24 %) ecosystems. Regarding the scale of intervention, 92 % of the case studies were operationalised at local (50 %) and watershed (46 %) scales while very few (4 %) were implemented at the landscape scale. The results also showed that 63 % of NBS have been used to deal with natural hazards, climate change, and loss of biodiversity, while the remaining 37 % address socio-economic challenges (e.g., economic development, social justice, inequality, and cohesion). Around 88 % of NBS implementations were supported by policies at the national level and the rest 12 % at local and regional levels. Most of the analysed cases contributed to Sustainable Development Goals 15, 13, and 6, and biodiversity strategic goals B and D. Case studies also highlighted the co-benefits of NBS: 64 % of them were environmental co-benefits (e.g., improving biodiversity, air and water qualities, and carbon storage) while 36 % were social (27 %) and economic (9 %) co-benefits. This synthesis of case studies helps to bridge the knowledge gap between scientists, policymakers, and practitioners, which can allow adopting and upscaling of NBS for disaster risk reduction and climate change adaptation and enhance their preference in decision-making processes.

Multimodality Imaging Evaluation to Detect Subtle Right Ventricular Involvement in Patients with Acute Myocarditis and Preserved Left Ventricular Ejection Fraction.

Background: Evaluation of the right ventricle (RV) in patients with acute myocarditis (MY) remains challenging with both 2D transthoracic echocardiography (TTE) and cardiovascular magnetic resonance (CMR). We examined the incremental diagnostic value of CMR feature tracking (FT) to evaluate RV involvement in patients with myocarditis. Methods: We enrolled 54 patients with myocarditis and preserved left ventricle (LV) ejection fraction (EF). The CMR protocol included T2-weighted images for edema detection and late gadolinium enhancement (LGE) images. Global longitudinal strain (GLS) of the left ventricle (LV) and RV free wall strain (CMR-FWS) were obtained with CMR-FT. We identified 34 patients (62%) with inferior and lateral segment (IL-MY) involvement and 20 (38%) noIL-MY in case of any other myocardial segment involved. Here, 20 individuals who underwent CMR for suspected cardiac disease, which was not confirmed thereafter, were considered as the control population. Results: TTE and CMR showed normal RV function in all patients without visible RV involvement at the LGE or T2-weighted sequences. At CMR, LV-GLS values were significantly lower in patients with MY compared to the control group (median -19.0% vs. -21.0%, p = 0.029). Overall, CMR RV-FWS was no different between MY patients and controls (median -21.2% vs. -23.2 %, p = 0.201) while a significant difference was found between RV FWS in IL-MY and noIL-MY (median -18.17% vs. -24.2%, p = 0.004). Conclusions: CMR-FT has the potential to unravel subclinical RV involvement in patients with acute myocarditis, specifically in those with inferior and lateral injuries that exhibit lower RV-FWS values. In this setting, RV deformation analysis at CMR may be effectively implemented for a comprehensive functional assessment.

Additional value of cardiac magnetic resonance feature tracking parameters for the evaluation of the arrhythmic risk in patients with mitral valve prolapse.

OBJECTIVES: The identification of patients with mitral valve prolapse (MVP) presenting high arrhythmic risk remains challenging. Cardiovascular Magnetic Resonance (CMR) feature tracking (FT) may improve risk stratification. We analyzed the role of CMR-FT parameters in relation to the incidence of complex ventricular arrhythmias (cVA) in patients with MVP and mitral annular disjunction (MAD). METHODS: 42 patients with MVP and MAD who underwent 1.5 T CMR were classified as MAD-cVA (n = 23, 55%) in case of cVA diagnosed on a 24-h Holter monitoring and as MAD-noVA in the absence of cVA (n = 19, 45%). MAD length, late gadolinium enhancement (LGE), basal segments myocardial extracellular volume (ECV) and CMR-FT were assessed. RESULTS: LGE was more frequent in the MAD-cVA group in comparison with the MAD-noVA group (78% vs 42%, p = 0.002) while no difference was observed in terms of basal ECV. Global longitudinal strain (GLS) was reduced in MAD-cVA compared to MAD-noVA (- 18.2% ± 4.6% vs - 25.1% ± 3.1%, p = 0.004) as well as global circumferential strain (GCS) at the mid-ventricular level (- 17.5% ± 4.7% vs - 21.6% ± 3.1%, p = 0.041). Univariate analysis identified as predictors of the incidence of cVA: GCS, circumferential strain (CS) in the basal and mid infero-lateral wall, GLS, regional longitudinal strain (LS) in the basal and mid-ventricular inferolateral wall. Reduced GLS [Odd ratio (OR):1.56 (confidence interval (CI) 95%: 1.45-2.47; p < 0.001)] and regional LS in the basal inferolateral wall [OR: 1.62 (CI 95%: 1.22-2.13; p < 0.001)] remained independent prognostic factors in multivariate analysis. CONCLUSION: In patients with MVP and MAD, CMR-FT parameters are correlated with the incidence of cVA and may be of interest in arrhythmic risk stratification.

The Role of Non-Invasive Multimodality Imaging in Chronic Coronary Syndrome: Anatomical and Functional Pathways.

Coronary artery disease (CAD) is one of the major causes of mortality and morbidity worldwide, with a high socioeconomic impact. Currently, various guidelines and recommendations have been published about chronic coronary syndromes (CCS). According to the recent European Society of Cardiology guidelines on chronic coronary syndrome, a multimodal imaging approach is strongly recommended in the evaluation of patients with suspected CAD. Today, in the current practice, non-invasive imaging methods can assess coronary anatomy through coronary computed tomography angiography (CCTA) and/or inducible myocardial ischemia through functional stress testing (stress echocardiography, cardiac magnetic resonance imaging, single photon emission computed tomography-SPECT, or positron emission tomography-PET). However, recent trials (ISCHEMIA and REVIVED) have cast doubt on the previous conception of the management of patients with CCS, and nowadays it is essential to understand the limitations and strengths of each imaging method and, specifically, when to choose a functional approach focused on the ischemia versus a coronary anatomy-based one. Finally, the concept of a pathophysiology-driven treatment of these patients emerged as an important goal of multimodal imaging, integrating 'anatomical' and 'functional' information. The present review aims to provide an overview of non-invasive imaging modalities for the comprehensive management of CCS patients.

Anatomical and Functional Outcomes after Endoresection and Adjuvant Ruthenium Brachytherapy for Uveal Melanoma: A Single-Center Experience.

PURPOSE: To evaluate the anatomical and functional outcomes of endoresection and adjuvant ruthenium (Ru)-106 brachytherapy for uveal melanoma (UM). METHODS: Retrospective case series of 15 UM patients (15 eyes) treated at our center (Careggi University Hospital, Florence). RESULTS: Six patients (40%) were male and nine were female (60%). The mean age of patients at the time of treatment was 61.6 years (±19.41). The mean BCVA at baseline was 20/50. In all cases UM originated from the choroid. The mean tumor thickness at baseline was 7.14 mm (±2.05), and the mean largest basal diameter was 11.2 mm (±1.92). A concurrent retinal detachment was diagnosed in 11 patients (73.3%). Two patients (13.3%) showed vitreous seeding at baseline. Eleven patients (73.3%) were treated with primary endoresection, while four patients (26.7%) were treated with a "salvage endoresection" after primary treatment failure (previous radiation treatment). The mean follow-up time was 28.9 months (±10.6). Thirteen out of fifteen patients were alive and showed no evidence of local recurrence or distance metastasis at the last follow-up visit. The treatment achieved local control of the disease in 14 out of 15 cases (93.3%). In one case, the patient underwent enucleation for disease recurrence. The overall survival rate at the end of the follow-up was 93.3%. The mean BCVA at last follow-up visit was 20/40. Treatment was well tolerated, without significant complications. CONCLUSIONS: Endoresection and adjuvant Ru-106 brachytherapy is a valuable conservative option for selected UM patients and can be used both as a primary treatment and as a salvage therapy. It can control melanoma and avoid enucleation, reduce radiation-related complications, and provide tumor tissue for chromosomal analysis and prognostic testing.

Mid-Term Clinical Outcomes and Hemodynamic Performances of Trifecta and Perimount Bioprostheses following Aortic Valve Replacement.

Aims of the Study: We evaluated the clinical outcome and the hemodynamic and freedom from structural valve degeneration of two standard aortic bioprostheses. Methods: Clinical results, echocardiographic findings and follow-up data of patients operated for isolated or combined aortic valve replacement with the Perimount or the Trifecta bioprosthesis were prospectively collected, retrospectively analysed and compared. We weighted all the analyses by the inverse of the propensity of choosing either valves. Results: Between April 2015 and December 2019, 168 consecutive patients (all comers) underwent aortic valve replacement with Trifecta (n = 86) or Perimount (n = 82) bioprostheses. Mean age was 70.8 ± 8.6 and 68.8 ± 8.6 years for the Trifecta and Perimount groups, respectively (p = 0.120). Perimount patients presented a greater body mass index (27.6 ± 4.5 vs. 26.0 ± 4.2; p = 0.022), and 23% of them suffered from angina functional class 2-3 (23.2% vs. 5.8%; p = 0.002). Mean ejection fraction was 53.7 ± 11.9% (Trifecta) and 54.5 ± 10.4% (Perimount) (p = 0.994), with mean gradients of 40.4 ± 15.9 mmHg (Trifecta) and 42.3 ± 20.6 mmHg (Perimount) (p = 0.710). Mean EuroSCORE-II was 7 ± 11% and 6 ± 9% for the Trifecta and Perimount group, respectively (p = 0.553). Trifecta patients more often underwent isolated aortic valve replacement (45.3% vs. 26.8%; p = 0.016) and annulus enlargement (10.5% vs. 2.4%; p = 0.058). All-cause mortality at 30 days was 3.5% (Trifecta) and 8.5% (Perimount), (p = 0.203) while new pacemaker implantation (1.2% vs. 2.5%; p = 0.609) and stroke rate (1.2% vs. 2.5%; p = 0.609) were similar. Acute MACCE were observed in 5% (Trifecta) and 9% (Perimount) of patients with an unweighted OR of 2.22 (95%CI 0.64-7.66; p = 0.196) and a weighted OR of 1.10 (95%CI: 0.44-2.76, p = 0.836). Cumulative survival at 24 months was 98% (95%CI: 0.91-0.99) and 96% (95%CI: 0.85-0.99) for Trifecta and Perimount groups, respectively (log-rank test; p = 0.555). The 2-year freedom from MACCE was 94% (95%CI: 0.65-0.99) for Trifecta and 96% (95%CI: 0.86-0.99) for Perimount (log-rank test; p = 0.759, HR 1.46 (95%CI: 0.13-16.48)) in the unweighted analysis (not estimable in the weighted analysis). During the follow-up (median time: 384 vs. 593 days; p = 0.0001) there were no re-operations for structural valve degeneration. Mean valve gradient at discharge was lower for Trifecta across all valve sizes (7.9 ± 3.2 vs. 12.1 ± 4.7 mmHg; p < 0.001), but the difference did not persist during follow-up (8.2 ± 3.7 mmHg for Trifecta, 8.9 ± 3.6 mmHg for Perimount; p = 0.224); Conclusions: Postoperative outcome and mid-term follow-up were similar. An early better hemodynamic performance was detected for the Trifecta valve but did not persist over time. No difference in the reoperation rate for structural valve degeneration was found.

The Role of Cardiovascular Magnetic Resonance in Patients with Mitral Regurgitation.

The 2019 Global Burden of Disease (GBD) study estimated that there were approximately 24.2 million people affected worldwide by degenerative mitral regurgitation (MR), resulting in 34,200 deaths. After aortic stenosis, MR is the most prevalent VHD in Europe and the second-most common VHD to pose indications for surgery in western countries. Current ESC and AHA/ACC guidelines for the management of VHD emphasize the importance of an integrative approach for the assessment of MR severity, which is of paramount importance in dictating the timing for surgery. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) are the first-line imaging modalities; however, despite the technological advancement, sometimes, the final diagnosis on the degree of the disease may still be challenging. In the last 20 years, CMR has emerged as a robust technique in the assessment of patients with cardiac disease, and, recently, its role is gaining more and more importance in the field of VHD. In fact, CMR is the gold standard in the assessment of cardiac volumes, and it is possible to accurately evaluate the regurgitant volume. The purpose of this review is to outline the current state-of-the-art management of MR by using Cardiac Magnetic Resonance (CMR).

Early Detection of Cardiotoxicity From Systemic and Radiation Therapy in Patients With Breast Cancer: Protocol for a Multi-Institutional Prospective Study.

BACKGROUND: The incidence of breast cancer is rising worldwide. Recent advances in systemic and local treatments have significantly improved survival rates of patients having early breast cancer. In the last decade, great attention has been paid to the prevention and early detection of cardiotoxicity induced by breast cancer treatments. Systemic therapy-related cardiac toxicities have been extensively studied. Radiotherapy, an essential component of breast cancer treatment, can also increase the risk of heart diseases. Consequently, it is important to balance the expected benefits of cancer treatment with cardiovascular risk and to identify strategies to prevent cardiotoxicity and improve long-term outcomes and quality of life for these patients. OBJECTIVE: This CardioTox Breast study aims to investigate the use of cardiac imaging, based on cardiac magnetic resonance and echocardiography, and to identify associated circulating biomarkers to assess early tissue changes in chemo-induced and radiation-induced cardiotoxicity in the time window of 12 months after the end of radiotherapy in patients with breast cancer. METHODS: The CardioTox Breast trial is a multicenter observational prospective longitudinal study. We aim to enroll 150 women with stage I-III unilateral breast cancer, treated with breast conserving surgery, who planned to receive radiotherapy with or without systemic therapy. Baseline and follow-up data include cardiac measurements based on cardiac magnetic resonance imaging, echocardiography, and circulating biomarkers of cardiac toxicity. RESULTS: This study details the protocol of the CardioTox Breast trial. Recruitment started in September 2020. The results of this study will not be published until data are mature for the final analysis of the primary study end point. CONCLUSIONS: The CardioTox Breast study is designed to investigate the effects of systemic and radiation therapy on myocardial function and structure, thus providing additional evidence on whether cardiac magnetic resonance is the optimal screening imaging for cardiotoxicity. TRIAL REGISTRATION: ClinicalTrials.gov NCT04790266; https://clinicaltrials.gov/ct2/show/NCT04790266. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31887.

Lactobacillus jensenii mitral valve endocarditis: Case report, literature review and new perspectives.

Lactobacillus is a facultative anaerobic Gram-positive rod usually found in the normal microbiota of the gastrointestinal and genitourinary tract. Frequently dismissed as a contaminant, it is implicated in several diseases. We describe a rare case of endocarditis caused by Lactobacillus jensenii in an immunocompetent 40 year-old male patient, with a history of mitral valve repair. He presented complaining of asthenia and his laboratory results showed a moderate increase in inflammatory markers. A trans-thoracic echocardiography confirmed a vegetation on the posterior leaflet of the mitral valve, with associated severe mitral insufficiency. Blood cultures revealed the significant growth of L. jensenii. The patient developed an acute abdomen with intestinal ischemia and occlusion of the superior mesenteric artery, requiring urgent surgical laparotomy. A cerebral MRI showed multiple minor emboli in the frontal and left parietal cortex. The patient consequently underwent surgery to have his mitral valve replaced with a mechanical valve. L. jensenii was isolated in culture from the mitral valve and from a mesenteric artery thrombus. After one week of combined amoxicillin and gentamicin therapy, ampicillin alone was continued for a total of six weeks and the patient could be discharged in a good general condition. Only five cases of L. jensenii are described in literature, and they mainly affect immunocompromised hosts. In our case, a long delay between the start of symptoms and the full onset of the disease was observed. tolerance of Lactobacilli to penicillin is a key determinant of therapy choice.

Trans-scleral plugs scleral fixation IOL and penetrating keratoplasty to restore vision in vitrectomized eyes.

PURPOSE: To report the surgical outcomes of penetrating keratoplasty (PKP) and sutureless scleral fixation (SSF) using Carlevale Lens (Soleko) combined procedure to solve corneal failure and aphakia in vitrectomized eyes and discuss eventual advantages of this new approach. METHODS: Two patients underwent primary wound repair and pars plana vitrectomy after a penetrating ocular trauma and were referred to the author's clinic. The PKP and SSF-Carlevale lens implantation were performed under retrobulbar anesthesia. Intraoperative and postoperative complications were recorded, intraocular lens positioning was evaluated using anterior segment optical coherence tomography (AS-OCT) and endothelial cell density was determined using an endothelial microscope. Both patients completed 12 months follow-up. RESULTS: The surgery was performed without intraoperative complications. After 1 month, the lens was fixed well, and the graft showed no sign of rejection. At the last visit after 12 months, the corneal graft remained transparent with good endothelial cell density in both cases; conjunctival scarring or inflammation and plugs externalization did not occur during follow-ups. Best-corrected visual acuity was 4/10 Snellen in the first case, while in the second case, we witnessed a limited visual recovery of 1/20 Snellen due to retinal issues. CONCLUSION: We report the feasibility of secondary IOL implantation using Carlevale with penetrating keratoplasty. The relative of ease of Carlevale lens implantation through the transscleral plugs reduces the open globe length resulting in a safer procedure, especially for vitrectomized eyes.

Management of submacular massive haemorrhage in age-related macular degeneration: comparison between subretinal transplant of human amniotic membrane and subretinal injection of tissue plasminogen activator.

PURPOSE: Macular neovascularization (MNV) can complicate age-related macular degeneration (AMD) and lead to severe visual acuity reduction. Massive submacular haemorrhage (SMH) is a sight-threatening complication of MNV and a challenge in the management of complications related to MNV in AMD since the effects of anti-vascular endothelial growth factor treatment alone are insufficient. Here, we evaluate the different postoperative outcomes of patients affected by MNV complicated by SMH that underwent subretinal implant of human amniotic membrane (hAM) or subretinal injection of tissue plasminogen activator (tPA). METHODS: This is a retrospective, consecutive, comparative, non-randomized interventional study. We included 44 eyes of 44 patients affected by AMD complicated by MNV and SMH. Twenty-two eyes underwent a pars plana vitrectomy (PPV), SMH and neovascular membrane removal, with a subretinal implant of hAM and silicone oil, and 22 eyes underwent PPV, subretinal injection of tPA, and 20% sulphur hexafluoride. The primary study outcome was visual acuity improvement. Secondary outcomes were postoperative complications, and MNV recurrence and optical coherence tomography (OCT)-Angiography parameters correlated with best-corrected visual acuity (BCVA). RESULTS: Mean preoperative BCVA was 1.9 logarithm of the minimal angle of resolution (logMAR) in the amniotic membrane-group and 2 logMAR in the tPA-group. The mean final BCVA values were 1.25 and 1.4 logMAR, respectively, with a statistically significant difference. Optical coherence tomography (OCT)-Angiography scan was be used to evaluate the retinal vascularization in the treated eye. CONCLUSION: Both techniques report similar VA improvements and postoperative complications. However, transplantation of hAM seems to have a significant benefit in inhibiting MNV recurrence.

Morphology of Mitral Annular Disjunction in Mitral Valve Prolapse.

Mitral annular disjunction (MAD) is an abnormal insertion of the hinge line of the posterior mitral leaflet on the atrial wall: the mitral annulus shows a separation or "disjunction" between the leaflet-atrial wall junction and the crest of the left ventricle myocardium. This anomaly is often observed in patients with myxomatous mitral valve prolapse. The anatomical substrate of MAD remains unclear for the following reasons: (1) most studies are focused on the association between MAD and arrhythmias, rather than on pathomorphological aspects of MAD; and (2) the complex anatomic architecture of the posterior mitral annulus is often simply described as the posterior segment of a fibrous ring. The aims of this paper are to review the pertinent normal anatomy of the mitral valve and to propose new hypotheses on the morphological nature of MAD.

Multimodality Imaging of the Anatomy of Tricuspid Valve.

Even though the tricuspid valve is no longer "forgotten", it still remains poorly understood. In this review, we focus on some controversial and still unclear aspects of tricuspid anatomy as illustrated by noninvasive imaging techniques. In particular, we discuss the anatomical architecture of the so-called tricuspid annulus with its two components (i.e., the mural and the septal annulus), emphasizing the absence of any fibrous "ring" around the right atrioventricular junction. Then we discussed the extreme variability in number and size of leaflets (from two to six), highlighting the peculiarities of the septal leaflet as part of the septal atrioventricular junction (crux cordis). Finally, we describe the similarities and differences between the tricuspid and mitral valve, suggesting a novel terminology for tricuspid leaflets.

Emerging Single-Cell Technological Approaches to Investigate Chromatin Dynamics and Centromere Regulation in Human Health and Disease.

Epigenetic regulators play a crucial role in establishing and maintaining gene expression states. To date, the main efforts to study cellular heterogeneity have focused on elucidating the variable nature of the chromatin landscape. Specific chromatin organisation is fundamental for normal organogenesis and developmental homeostasis and can be affected by different environmental factors. The latter can lead to detrimental alterations in gene transcription, as well as pathological conditions such as cancer. Epigenetic marks regulate the transcriptional output of cells. Centromeres are chromosome structures that are epigenetically regulated and are crucial for accurate segregation. The advent of single-cell epigenetic profiling has provided finer analytical resolution, exposing the intrinsic peculiarities of different cells within an apparently homogenous population. In this review, we discuss recent advances in methodologies applied to epigenetics, such as CUT&RUN and CUT&TAG. Then, we compare standard and emerging single-cell techniques and their relevance for investigating human diseases. Finally, we describe emerging methodologies that investigate centromeric chromatin specification and neocentromere formation.

Multimodality Imaging of the Anatomy of the Aortic Root.

The aortic root has long been considered an inert unidirectional conduit between the left ventricle and the ascending aorta. In the classical definition, the aortic valve leaflets (similar to what is perceived for the atrioventricular valves) have also been considered inactive structures, and their motion was thought to be entirely passive-just driven by the fluctuations of ventricular-aortic gradients. It was not until the advent of aortic valve-sparing surgery and of transcatheter aortic valve implantation that the interest on the anatomy of the aortic root again took momentum. These new procedures require a systematic and thorough analysis of the fine anatomical details of the components of the so-called aortic valve apparatus. Although holding and dissecting cadaveric heart specimens remains an excellent method to appreciate the complex "three-dimensional" nature of the aortic root, nowadays, echocardiography, computed tomography, and cardiac magnetic resonance provide excellent images of cardiac anatomy both in two- and three-dimensional format. Indeed, modern imaging techniques depict the aortic root as it is properly situated within the thorax in an attitudinally correct cardiac orientation, showing a sort of "dynamic anatomy", which admirably joins structure and function. Finally, they are extensively used before, during, and after percutaneous structural heart disease interventions. This review focuses on the anatomy of the aortic root as revealed by non-invasive imaging techniques.