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Background: Transcatheter treatments for structural heart disease, including edge-to-edge mitral valve repair (mTEER), heavily rely on transoesophageal echocardiography (TOE) for pre-procedural assessment and guidance. Trans-septal puncture (TSP) is one of the first key steps of such procedures, with two-dimensional (2D) TOE often providing suboptimal imaging. Three-dimensional (3D) echocardiography could overcome the limitations of 2D TOE and improve the assessment of tenting height. Methods: This single-centre, retrospective study included 64 patients who underwent mTEER between October 2023 and April 2024. Tenting height during TSP was assessed by 2D TOE in mid-oesophageal (ME) four-chamber view and by 3D TOE after the acquisition of a 3D volume, including the interatrial septum, aortic valve, and mitral valve, and subsequent multiplanar reconstruction (MPR). A total of 100 TSP attempts with 2D and 3D TOE were evaluated. Results: Procedural success was obtained in 92.2% of cases. There was a statistically significant difference between 2D and 3D measurements (2D: 4.36 ± 0.61 cm, MPR: 4.59 ± 0.63 mm2, p < 0.001), despite good correlation (r = 0.880, p < 0.001). The difference between 2D and 3D tenting height measurements differed significantly between patients with optimal and suboptimal 2D image windows (p < 0.001). There was no significant difference in septal puncture success between optimal 2D and 3D data (p = 0.942). Conclusions: Adopting 3D TOE with multiplanar reconstruction for assessing tenting height in mTEER procedures offers significant advantages over traditional 2D TOE. Enhanced visualization, accuracy, and potential for standardization improve procedural outcomes and patient safety, making 3D TOE integration into routine practice highly beneficial and recommended. [ABSTRACT FROM AUTHOR]

In acute myocardial infarction (AMI), the urgency of coronary revascularization through percutaneous coronary intervention (PCI) is paramount, offering notable advantages over pharmacologic treatment. However, the persistent risk of adverse events, including recurrent AMI and heart failure post-revascularization, underscores the necessity for enhanced strategies in managing coronary artery disease. Traditional angiography, while widely employed, presents significant limitations by providing only two-dimensional representations of complex three-dimensional vascular structures, hampering the accurate assessment of plaque characteristics and stenosis severity. Intravascular imaging, specifically optical coherence tomography (OCT), significantly addresses these limitations with superior spatial resolution compared to intravascular ultrasound (IVUS). Within the context of AMI, OCT serves dual purposes: as a diagnostic tool to accurately identify culprit lesions in ambiguous cases and as a guide for optimizing PCI procedures. Its capacity to differentiate between various mechanisms of acute coronary syndrome, such as plaque rupture and spontaneous coronary dissection, enhances its diagnostic potential. Furthermore, OCT facilitates precise lesion preparation, optimal stent sizing, and confirms stent deployment efficacy. Recent meta-analyses indicate that OCT-guided PCI markedly improves safety and efficacy in revascularization, subsequently decreasing the risks of mortality and complications. This review emphasizes the critical role of OCT in refining patient-specific therapeutic approaches, aligning with the principles of precision medicine to enhance clinical outcomes for individuals experiencing AMI. [ABSTRACT FROM AUTHOR]

Background: The mismatch between tricuspid valve (TV) leaflet length and annulus dilation, assessed with the septal–lateral leaflet-to-annulus index (SL-LAI), predicts residual tricuspid regurgitation (TR) following tricuspid transcatheter edge-to-edge-repair (T-TEER). When posterior leaflet grasping is required, the anterior–posterior leaflet-to-annulus index (AP-LAI) may offer additional information. Methods: This single-center retrospective cohort study included all patients referred for T-TEER with severe and symptomatic TR with high surgical risk from April 2021 to March 2024. Patients were categorized into 'optimal result' (

Metabolic Syndrome (MetS), a multifactorial condition that increases the risk of cardiovascular events, is frequent in Heart-transplant (HTx) candidates and worsens with immunosuppressive therapy. The aim of the study was to analyze the impact of MetS on long-term outcome of HTx patients. Since 2007, 349 HTx patients were enrolled. MetS was diagnosed if patients met revised NCEP-ATP III criteria before HTx, at 1, 5 and 10 years of follow-up. MetS was present in 35% of patients pre-HTx and 47% at 1 year follow-up. Five-year survival in patientswith both pre-HTx (65%vs. 78%, p < 0.01) and 1 year follow-up MetS (78% vs 89%, p < 0.01) was worst. At the univariate analysis, risk factors for mortality were pre-HTx MetS (HR 1.86, p < 0.01), hypertension (HR 2.46, p < 0.01), hypertriglyceridemia (HR 1.50, p=0.03), chronic renal failure (HR 2.95, p < 0.01), MetS and diabetes at 1 year follow-up (HR2.00, p < 0.01; HR 2.02, p < 0.01, respectively). MetS at 1 year follow-up determined a higher risk to develop Coronary allograft vasculopathy at 5 and 10 year follow-up (25%vs 14%and 44%vs 25%, p < 0.01). MetS is an important risk factor for both mortality and morbidity post-HTx, suggesting the need for a strict monitoring of metabolic disorders with a careful nutritional follow-up in HTx patients. [ABSTRACT FROM AUTHOR]

Introduction: Heart transplant (HTx) recipients require continuous monitoring and care in order to prevent and treat possible complications related to the graft function or to the immunosuppressive treatment promptly. Since heart transplantation centers (HTC) are more experienced in managing HTx recipients than other healthcare facilities, the distance between patient residency and HTC could negatively affect the outcomes. Methods: Data of patients discharged after receiving HTx between 2000 and 2021, collected into our institutional database, were retrospectively analyzed. The population was divided into three groups: A (n = 180), B (n = 157), and C (n = 134), according to the distance tertiles between patient residency and HTC. The primary end‐point was survival, secondary end‐points were incidences of complications. Results: Recipient and donor characteristics did not differ between the three groups. Survival at 10 years was 66 ± 4%, 66 ± 4%, and 65 ± 5%, respectively, for groups A, B, and C (p =.34). Immunosuppressive regimen and rate of complications did not differ between groups. However, the rates of outpatient visits and of hospitalization performed at HTC were higher in group A than others. Conclusion: Distance from the HTC does not represent a barrier to a successful outcome for HTx recipients, as long as regular and continuous follow‐up is provided. [ABSTRACT FROM AUTHOR]

An automatic geomagnetic station for monitoring the Earth's magnetic field variations was installed in December 2020 at Talos Dome, a remote site on the Antarctic Plateau, about 300 km away from the permanent geomagnetic observatory at Mario Zucchelli Station (MZS). Designed and assembled at the laboratory of electronics of the Istituto Nazionale di Geofisica e Vulcanologia (INGV) in Rome, this autonomous station is formed by a vector magnetometer specifically manufactured by Lviv Institute (Ukraine) for very low temperatures and a low-power system supplied by batteries charged by a wind generator and solar panel. Data, sampled at 1 Hz, are locally stored and can be downloaded once a year during the Antarctic summer expeditions. The goal was to integrate observatory data for better monitoring the geomagnetic field from an uncovered Antarctic area. In fact, it is well known that the distribution of geomagnetic observatories strongly favors the northern hemisphere, and each new instrumental installation in Antarctica should be considered as a useful attempt to balance the geomagnetic monitoring in the two hemispheres. The achieved goal was to obtain a long data series, keeping the station working even during the austral winter when the temperature can reach −60 °C; we recorded almost 11 months of data in one year and the station is still operating. Data from the new station, jointly with data from permanent observatories, improve the analysis of the magnetospheric dynamics and the ionosphere–magnetosphere coupling. Talos Dome, together with the Italian geomagnetic observatory at Mario Zucchelli Station and New Zealand geomagnetic observatory at Scott Base, constitutes a network along the 80°S geomagnetic parallel, which is interesting for studying the longitudinal propagation of geomagnetic signals of external origin. In this work we present the characteristics of the station and of the data it provides, with the aim of them for analysis in the framework of space weather. [ABSTRACT FROM AUTHOR]

Left ventricular assist device (LVAD) has emerged as an effective surgical therapy for end‐stage heart failure. In an attempt to reduce invasiveness and avoid difficult sternal re‐entries, alternative surgical approaches have been adopted. In particular, when the thoracic aorta is severely diseased or difficult to expose, subclavian arteries could serve as site for outflow graft anastomosis. However, major concerns regarding the utilization of subclavian arteries are the small caliber of these vessels that could lead to inadequate LVAD flow, arm complications related to excessive blood flow, and possible outflow graft compression. In the present case series, we describe an innovative technique for LVAD implantation, in which the left subclavian artery was employed as an outflow graft anastomosis site, and the left ventricular apex was approached through a mini‐thoracotomy. Technical issues were considered to prevent possible complications: the adequacy of left subclavian artery diameter, the banding of the artery distal to the anastomosis site to limit left arm overflow, and the outflow graft covering with a reinforced vascular graft to avoid any external compression. During follow‐up, the technique reported was found to be effective in ensuring good LVAD function and flow, and no complications related to the procedure were reported. [ABSTRACT FROM AUTHOR]

Background: Improving cancer immunotherapy long-term clinical benefit is a major priority. It has become apparent that multiple axes of immune suppression restrain the capacity of T cells to provide anti-tumour activity including signalling through PD1/PD-L1 and LAG3/MHC-II.Methods: CB213 has been developed as a fully human PD1/LAG3 co-targeting multi-specific Humabody composed of linked VH domains that avidly bind and block PD1 and LAG3 on dual-positive T cells. We present the preclinical primary pharmacology of CB213: biochemistry, cell-based function vs. immune-suppressive targets, induction of T cell proliferation ex vivo using blood obtained from NSCLC patients, and syngeneic mouse model anti-tumour activity. CB213 pharmacokinetics was assessed in cynomolgus macaques.Results: CB213 shows picomolar avidity when simultaneously engaging PD1 and LAG3. Assessing LAG3/MHC-II or PD1/PD-L1 suppression individually, CB213 preferentially counters the LAG3 axis. CB213 showed superior activity vs. αPD1 antibody to induce ex vivo NSCLC patient T cell proliferation and to suppress tumour growth in a syngeneic mouse tumour model, for which both experimental systems possess PD1 and LAG3 suppressive components. Non-human primate PK of CB213 suggests weekly clinical administration.Conclusions: CB213 is poised to enter clinical development and, through intercepting both PD1 and LAG3 resistance mechanisms, may benefit patients with tumours escaping front-line immunological control. [ABSTRACT FROM AUTHOR]

Objective: The coronavirus disease 2019 (COVID‐19) outbreak has been declared a global pandemic of unprecedented proportions. Italy is a country which has been heavily affected. Cancer patients are at a higher risk owing to their intrinsic fragility related to their underlying disease and oncologic treatment. Against this backdrop, we conducted a survey to investigate how patients perceived their condition, clinical management and availability of information during the pandemic. Methods: Between 15 April and 1 May 2020 a survey was submitted to cancer patients at oncology departments in the Marche region. Questions regarding the perception of personal safety, continuity of cancer care, information quality and psychological distress. Results: Seven hundred patients participated in the survey; 59% were female and 40% were aged between 46 and 65. The majority of the participants perceived compliance with appropriate safety standards by cancer care providers and 80% were reassured about their concerns during the medical interview. 40% were worried of being at a higher risk of infection and 71% felt they were at a greater risk because of chemotherapy. 55% felt that postponing cancer treatment could reduce its efficacy, however 76% declared they did not feel abandoned at the time of treatment postponement. Patients between 46 and 65 years declared a significant reduction in sleep (p < 0.01) and in concentration (p = 0.03). Conclusions: The emergency care offered to cancer patients has been deemed satisfactory in terms of both safety standards and care management. However, the majority of participants perceived the mutual negative influence between their oncologic disease and the risk of infection highlighting the need for special measures to ensure safe continuity of care. [ABSTRACT FROM AUTHOR]

An 83-year-old man had aortic valve replacement for aortic stenosis with a pericardial bioprosthesis and subsequent implantation of a CoreValve™ prosthesis as a valve-in-valve procedure. Approximately 4 years later, he developed endocarditis on the CoreValve™ with severe prosthetic stenosis, a periannular abscess and systemic embolization. At reoperation both prostheses were removed and another bioprosthesis inserted after reconstruction of the aortic root. Endocarditis after transaortic valve implantation is an uncommon event with dismal prognosis. Infection of a self-expandable device as a valve-in-valve has not been previously reported. This complication represents a surgical challenge which, however, can be successfully managed. [ABSTRACT FROM AUTHOR]

Safety of pregnancy in women with history of estrogen receptor (ER)-positive breast cancer remains controversial. In this multicenter case-control study, 333 patients with pregnancy after breast cancer were matched (1:3) to 874 nonpregnant patients of similar characteristics, adjusting for guaranteed time bias. Survival estimates were calculated using the Kaplan-Meier analysis; groups were compared with the log-rank test. All reported P values were two-sided. At a median follow-up of 7.2 years after pregnancy, no difference in disease-free survival was observed between pregnant and nonpregnant patients with ER-positive (hazard ratio [HR] = 0.94, 95% confidence interval [CI] = 0.70 to 1.26, P = .68) or ER-negative (HR = 0.75, 95% CI = 0.53 to 1.06, P = .10) disease. No overall survival (OS) difference was observed in ER-positive patients (HR = 0.84, 95% CI = 0.60 to 1.18, P = .32); ER-negative patients in the pregnant cohort had better OS (HR = 0.57, 95% CI = 0.36 to 0.90, P = .01). Abortion, time to pregnancy, breastfeeding, and type of adjuvant therapy had no impact on patients' outcomes. This study provides reassuring evidence on the long-term safety of pregnancy in breast cancer survivors, including those with ER-positive disease. [ABSTRACT FROM AUTHOR]

The authors present the case of a heavily pretreated young woman with retinal and brain metastases from breast cancer who was successfully treated with eribulin. Eribulin was given at 1.1 mg/m2 on day 1 and 8, every 3 weeks for a total of 12 courses. A significant reduction in the size of brain and retinal lesions was achieved after three cycles. The treatment was continued for 12 cycles, with a good profile of tolerability. In this clinical case, eribulin demonstrated to be active on brain and retinal metastases from breast cancer, although preclinical data showed limited ability to cross the blood-brain barrier. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented commenting on long-term Trastuzumab therapy in metastatic breast cancer.

Glioblastoma multiforme (GBM) is composed of heterogeneous and genetically different cells, which are highly invasive and motile. The standard chemotherapeutic agent, temozolomide, affects GBM cell proliferation but is generally unable to prevent tumor recurrence. Hedgehog pathway activation has been reported to be relevant in GBM and different pharmacological pathway modulators have been identified. We report that by growing a commercially available recurrent GBM cell line (DBTRG-05MG) without serum and in the presence of defined growth factors; we obtained a less differentiated cell population, growing in suspension as neurospheres, in which the Hedgehog pathway is activated. Furthermore, the expression profile of Hedgehog pathway components found in DBTRG-05MG neurospheres is similar to primary stem-like cells derived from recurrent GBM patients. We report the effect of our novel specific Smoothened receptor antagonist (SEN450) on neurosphere growing cells and compared its effect to that of well known benchmark compounds. Finally, we showed that SEN450 is both antiproliferative on its own and further reduces tumor volume after temozolomide pretreatment in a mouse xenograft model using DBTRG-05MG neurosphere cells. Altogether our data indicate that the Hedgehog pathway is not irreversibly switched off in adherent cells but can be reactivated when exposed to well-defined culture conditions, thus restoring the condition observed in primary tumor-derived material, and that pharmacological modulation of this pathway can have profound influences on tumor proliferation. Therefore, pharmacological inhibition of the Hedgehog pathway is a potentially useful therapeutic approach in GBM. [ABSTRACT FROM AUTHOR]

Examines whether low-molecular-weight heparin can improve the outcome of patients with operable non-small cell lung cancer. Surgery and therapeutic advances; Impact on survival of adjuvant platinum-based chemotherapy; Effectiveness of heparins in both prevention and treatment of venous thromboembolism (VTE); Effects on cellular growth; Effects on blood coagulation pathway and platelet aggregation.

Regular automatic recordings of the time series of the magnetic field, together with routine manual absolute measurements for establishing dynamic baselines at Lampedusa Island—south of Sicily—Italy (geographic coordinates 35°31′N; 12°32′E, altitude 33 m a.s.l.), show a signature of very low electromagnetic noise. The observatory (provisional IAGA code: LMP) lays inside a restricted and remote wildlife reserve, far away from the built-up and active areas of the island, which at present is the southernmost location of the European territory for such observations. The availability of high-quality data from such site, whose survey started in 2005, is valuable for filling the spatial gap due to the lack of observatories in the whole south Mediterranean and North African sectors. We compare observations at Lampedusa, in both time and frequency domains, with those at the other Italian observatories (Castello Tesino and Duronia-L'Aquila), operating since the 1960s of last century, allowing us to report even the secular variation. Using data recorded in the last few years, we investigate higher frequency variations (from diurnal to Pc3-4 pulsations) in order to magnetically characterize the Italian territory and the local response to external forcing. In particular, we present a characterization in terms of diurnal variation and its seasonal dependence for the three observatories. This latter feature is in good agreement with a geomagnetic Sq-model, leading us to speculate about the position of the north Sq-current system vortex and its seasonal displacement with respect to the geographic positions of the observatories. We also study the geomagnetic individual response to intense space weather events by performing Superposed Epoch Analysis (SEA), with an ad-hoc significance test. Magnetic responses in the Ultra Low Frequency range (ULF) from spectral, local Signal-to-Noise Ratio (SNR) analyses under different local time, and polarization rates are computed. These latter studies lead us to search for possible signatures of magnetic field line resonances during intense space weather events, using cross-phase multi-observatory analysis, revealing the promising detection capability of such technique even at low latitudes. The geomagnetic observatories prove to be important points of observation for space weather events occurring at different spatial and time scales, originating in both upstream and ionospheric regions, here analyzed by several well-established methodologies and techniques. The quiet environmental site of LMP, providing high-quality geomagnetic data, allows us such investigations even at inner Earth's magnetospheric shell. [ABSTRACT FROM AUTHOR]

Heart transplantation remains the gold standard treatment for end-stage heart failure. To face actual donor shortage, heart warm perfusion with the Organ Care System (OCS) was introduced alternatively to usual cold ischemic storage [1]. Here, OCS-preserved hearts were matched against those subjected to cold ischemia in terms of (i) perioperative clinical parameters, (ii) histopathological, immunohistochemical, and ultrastructural features of pre- and post-implant left ventricle biopsies, and (iii) cardiomyocyte metabolism by NMR spectroscopy of blood samples. Concerning clinical outcomes and myocardium structural preservation, preliminary data seem to be encouraging. Namely, NMR spectra revealed OCS perfusion to reduce cardiomyocyte oxidative stress by lowering the lactate/glucose ratio. Ultrastructurally, cardiomyocytes from OCS-preserved hearts showed minor hypertrophy signs and few altered mitochondria. OCS preservation also seemed to mitigate reperfusion effects, decreasing the number of degenerating cardiomyocytes. Interestingly, disappearance of sarcomere banding in one heart undergone pre-explant arrest was found to be restored after OCS perfusion. In conclusion, these preliminary data suggest that the OCS can improve heart storage. Functional recovery of borderline hearts with actual broadening of the donor pool seems to represent additional advantages of OCS technology. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Low-Molecular-Weight Heparin and Outcomes" published in the previous issue.