Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe.

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.

KIT/PDGFRA Variant Allele Frequency as Prognostic Factor in Gastrointestinal Stromal Tumors (GISTs): Results From a Multi-Institutional Cohort Study.

BACKGROUND: The patient selection for optimal adjuvant therapy in gastrointestinal stromal tumors (GISTs) is provided by nomogram based on tumor size, mitotic index, tumor location, and tumor rupture. Although mutational status is not currently used to risk assessment, tumor genotype showed a prognostic influence on natural history and tumor relapse. Innovative measures, such as KIT/PDGFRA-mutant-specific variant allele frequency (VAF) levels detection from next-generation sequencing (NGS), may act as a surrogate of tumor burden and correlate with prognosis and overall survival of patients with GIST, helping the choice for adjuvant treatment. PATIENTS AND METHODS: This was a multicenter, hospital-based, retrospective/prospective cohort study to investigate the prognostic role of KIT or PDGFRA-VAF of GIST in patients with radically resected localized disease. In the current manuscript, we present the results from the retrospective phase of the study. RESULTS: Two-hundred (200) patients with GIST between 2015 and 2022 afferent to 6 Italian Oncologic Centers in the EURACAN Network were included in the study. The receiver operating characteristic (ROC) curves analysis was used to classify "low" vs. "high" VAF values, further normalized on neoplastic cellularity (nVAF). When RFS between the low and high nVAF groups were compared, patients with GIST with KIT/PDGFRA nVAF > 50% showed less favorable RFS than patients in the group of nVAF ≤ 50% (2-year RFS, 72.6% vs. 93%, respectively; P = .003). The multivariable Cox regression model confirmed these results. In the homogeneous sub-population of intermediate-risk, patients with KIT-mutated GIST, the presence of nVAF >50% was statistically associated with higher disease recurrence. CONCLUSION: In our study, we demonstrated that higher nVAF levels were independent predictors of GIST prognosis and survival in localized GIST patients with tumors harboring KIT or PDGFRA mutations. In the cohort of intermediate-risk patients, nVAF could be helpful to improve prognostication and the use of adjuvant imatinib.

Sex and survival outcomes in patients with renal cell carcinoma receiving first-line immune-based combinations.

BACKGROUND: There is an ongoing debate as to whether sex could be associated with immune checkpoint inhibitor (ICI) benefit. Existing literature data reveal contradictory results, and data on first-line immune combinations are lacking. METHOD: This was a real-world, multicenter, international, observational study to determine the sex effects on the clinical outcomes in metastatic renal cell carcinoma (mRCC) patients treated with immuno-oncology combinations as first-line therapy. RESULTS: A total of 1827 mRCC patients from 71 cancer centers in 21 countries were included. The median OS was 38.7 months (95% CI 32.7-44.2) in the overall study population: 40.0 months (95% CI 32.7-51.6) in males and 38.7 months (95% CI 26.4-41.0) in females (p = 0.202). The median OS was higher in males vs. females in patients aged 18-49y (36.9 months, 95% CI 29.0-51.6, vs. 24.8 months, 95% CI 16.8-40.4, p = 0.426, with + 19% of 2y-OS rate, 72% vs. 53%, p = 0.006), in the clear cell histology subgroup (44.2 months, 95% CI 35.8-55.7, vs. 38.7 months, 95% CI 26.0-41.0, p = 0.047), and in patients with sarcomatoid differentiation (34.4 months, 95% CI 26.4-59.0, vs. 15.3 months, 95% CI 8.9-41.0, p < 0.001). Sex female was an independent negative prognostic factor in the sarcomatoid population (HR 1.72, 95% CI 1.15 - 2.57, p = 0.008). CONCLUSIONS: Although the female's innate and adaptive immunity has been observed to be more active than the male's, women in the subgroup of clear cell histology, sarcomatoid differentiation, and those under 50 years of age showed shorter OS than males.

Pulsed field ablation technology for pulmonary vein and left atrial posterior wall isolation in patients with persistent atrial fibrillation.

INTRODUCTION: Limited data exist on pulsed-field ablation (PFA) in patients with persistent atrial fibrillation (PeAF) undergoing left atrial posterior wall isolation (LAPWI). METHODS: The Advanced TecHnologies For SuccEssful AblatioN of AF in Clinical Practice (ATHENA) prospective registry included consecutive patients referred for PeAF catheter ablation at 9 Italian centers, treated with the FARAPULSETM-PFA system. The primary efficacy and safety study endpoints were the acute LAPWI rate, freedom from arrhythmic recurrences and the incidence of major periprocedural complications. Patients undergoing pulmonary vein isolation (PVI) alone, PWI + LAPWI and redo procedures were compared. RESULTS: Among 249 patients, 21.7% had long-standing PeAF, 79.5% were male; mean age was 63 ± 9 years. LAPWI was performed in 57.6% of cases, with 15.3% being redo procedures. Median skin-to-skin times (PVI-only 68 [60-90] vs. PVI + LAPWI 70 [59-88] mins) did not differ between groups. 45.8% LAPWI cases were approached with a 3D-mapping system, and 37.3% with intracardiac echocardiography. LAPWI was achieved in all patients by means of PFA alone, in 88.8% cases at first pass. LAPWI was validated either by an Ultrahigh-density mapping system or by recording electrical activity + pacing maneuvers. No major complications occurred, while 2.4% minor complications were detected. During a median follow-up of 273 [191-379] days, 41 patients (16.5%) experienced an arrhythmic recurrence after the 90-day blanking period, with a mean time to recurrence of 223 ± 100 days and no differences among ablation strategies. CONCLUSION: LAPWI with PFA demonstrates feasibility, rapidity, and safety in real-world practice, offering a viable alternative for PeAF patients. LAPWI is achievable even with a fluoroscopy-only method and does not significantly extend overall procedural times.

Altered domain-specific striatal functional connectivity in patients with Parkinson's disease and urinary symptoms.

BACKGROUND: In this study, we aimed at investigating the possible association of urinary symptoms with whole-brain MRI resting-state functional connectivity (FC) alterations from distinct striatal subregions in a large cohort of early PD patients. METHODS: Seventy-nine drug-naive PD patients (45 PD-urinary+/34 PD-urinary-) and 38 healthy controls (HCs) were consecutively enrolled. Presence/absence of urinary symptoms were assessed by means of the Nonmotor Symptom Scale - domain 7. Using an a priori connectivity-based domain-specific parcellation, we defined three ROIs (per each hemisphere) for different striatal functional subregions (sensorimotor, limbic and cognitive) from which seed-based FC voxel-wise analyses were conducted over the whole brain. RESULTS: Compared to PD-urinary-, PD-urinary+ patients showed increased FC between striatal regions and motor and premotor/supplementary motor areas as well as insula/anterior dorsolateral PFC. Compared to HC, PD-urinary+ patients presented decreased FC between striatal regions and parietal, insular and cingulate cortices. CONCLUSIONS: Our findings revealed a specific pattern of striatal FC alteration in PD patients with urinary symptoms, potentially associated to altered stimuli perception and sensorimotor integration even in the early stages. These results may potentially help clinicians to design more effective and tailored rehabilitation and neuromodulation protocols for PD patients.

Are autopsies on minors a taboo?: The experience of Milan in a 19-year retrospective study.

Forensic autopsy is an important tool for the proper management of non-natural deaths in minors. However, it seems that autopsy in minors is a practice which may not be performed routinely. In this framework, we conducted a study analyzing autopsies of minors (under 18 years of age in Italy) performed at the Institute of Forensic Medicine in Milan in the period 2001-2019. For the period 2015-2019, we extrapolated all deaths due to non-natural causes in minors to investigate how many and which of these deaths were not subjected to forensic autopsy. Of the total, 344 minors (235 males and 109 females) underwent autopsies, with an overall downward trend of about 80% since 2004. Most autopsies occurred between the ages of 0 and 1 year, and the fewest between the ages of 5 and 9 years. The place of death was home in most cases, and accidental death was most common, followed by natural death, suicide, and homicide, with prevalence varying by age group. Blunt force trauma predominated among accidental death in all age groups, followed by asphyxia. Similar findings were observed for suicides, although there was a more differentiated pattern for suicides between the ages of 15 and 17 years. Among homicides, blunt force trauma, asphyxia, and gunshot wounds were fairly evenly distributed across all age groups. Between 2015 and 2019, a total of 86 minors died of a non-natural cause, and a forensic autopsy was performed in only 33 cases (38%). Our data shows that fewer and fewer autopsies are being performed over the last years, which indicates a dangerous lack of forensic investigation of children and adolescent deaths, with enormous implications for prevention of child abuse.

Clinical and epidemiological factors causing longer SARS-CoV 2 viral shedding: the results from the CoviCamp cohort.

INTRODUCTION: The aim of this study was to investigate how long hospitalized patients stayed positive to the nasopharyngeal swab, and what demographic and clinical factors influence the time-to-negative swab. METHODS: We enrolled in a multicenter, observational, retrospective study involving 17 COVID-19 units in eight cities of the Campania, southern Italy all patients hospitalized from March 2020 to May 2021 diagnosed with Severe Acute Respiratory Distress Syndrome-Coronavirus-2 (SARS-CoV-2) infection for whom time-to-negative swab was available. RESULTS: 963 patients were enrolled. We defined three groups considering time-to-negative swab: the first including patients with time-to-negative swab before the 26th day, the second including patients with time-to-negative swab from day 26 to day 39, and the third including patients with time-to-negative swab > 39 days. 721 (74.9%) patients belonged to the first group, 194 (20.1%) to the second, and 52 (5.4%) belonged to the third group. Belonging to group 2 and 3 seemed to be influenced by age (p value < 0.001), Charlson comorbidity index (p = 0.009), arterial hypertension (p = 0.02), cardiovascular disease (p = 0.017), or chronic kidney disease (CKD) (p = 0.001). The multivariable analysis confers a leading role to CKD, with an odds ratio of 2.3 as factor influencing belonging to the groups showing a longer time-to-negative swab. Patients with CKD and diabetes were more frequently in the third group. DISCUSSION: Our analysis showed that CKD is a factor related to longer time-to-negative swab, probably because of immunosuppression related to this condition.

Impact of ventricular tachycardia ablation in subcutaneous implantable cardioverter defibrillator carriers: a multicentre, international analysis from the iSUSI project.

AIMS: Catheter ablation (CA) of ventricular tachycardia (VT) has become an important tool to improve clinical outcomes in patients with appropriate transvenous implantable cardioverter defibrillator (ICD) shocks. The aim of our analysis was to test whether VT ablation (VTA) impacts long-term clinical outcomes even in subcutaneous ICD (S-ICD) carriers. METHODS AND RESULTS: International Subcutaneous Implantable Cardioverter Defibrillator (iSUSI) registry patients who experienced either an ICD shock or a hospitalization for monomorphic VT were included in this analysis. Based on an eventual VTA after the index event, patients were divided into VTA+ vs. VTA- cohorts. Primary outcome of the study was the occurrence of a combination of device-related appropriate shocks, monomorphic VTs, and cardiovascular mortality. Secondary outcomes were addressed individually. Among n = 1661 iSUSI patients, n = 211 were included: n = 177 experiencing ICD shocks and n = 34 hospitalized for VT. No significant differences in baseline characteristics were observed. Both the crude and the yearly event rate of the primary outcome (5/59 and 3.8% yearly event rate VTA+ vs. 41/152 and 16.4% yearly event rate in the VTA-; log-rank: P value = 0.0013) and the cardiovascular mortality (1/59 and 0.7% yearly event rate VTA+ vs. 13/152 and 4.7% yearly event rate VTA-; log-rank P = 0.043) were significantly lower in the VTA + cohort. At multivariate analysis, VTA was the only variable remaining associated with a lower incidence of the primary outcome [adjusted hazard ratio 0.262 (0.100-0.681), P = 0.006]. CONCLUSION: In a real-world registry of S-ICD carriers, the combined study endpoint of arrhythmic events and cardiovascular mortality was lower in the patient cohort undergoing VTA at long-term follow-up. CLINICALTRIALS.GOV IDENTIFIER: NCT0473876.

The first interim analysis of Italian patients enrolled in the real-world, Pan-European, prospective, observational, phase 4 PEARL study of fremanezumab effectiveness.

INTRODUCTION: In 2020, the Italian Medicines Agency (AIFA) approved the reimbursement of calcitonin gene-related peptide (CGRP) pathway monoclonal antibodies (mAbs), including fremanezumab, in patients with a Migraine Disability Assessment Scale (MIDAS) score ≥ 11, with prescription renewals for up to 12 months in patients with ≥ 50% reduction in MIDAS score at Months 3 and 6. In this sub-analysis of the Pan-European Real Life (PEARL) study, we provide real-world data on fremanezumab use in Italian routine clinical practice (EUPAS35111). METHODS: This first interim analysis for Italy was conducted when 300 enrolled adult patients with episodic or chronic migraine (EM, CM) completed 6 months of treatment with fremanezumab. The primary endpoint is the proportion of patients achieving ≥ 50% reduction in monthly migraine days (MMD) across the 6 months post-fremanezumab initiation. Secondary endpoints include: proportion of patients achieving ≥ 50% reduction in MIDAS score at Months 3 and 6, and mean change from baseline across Months 1-6 in MMD and headache-related disability. Safety was assessed through adverse events (AEs) reported. RESULTS: Of 354 patients enrolled at Italian centers, 318 (EM, 35.5%, CM, 64.5%) were included in the effectiveness analysis. Of patients with available data, 109 (61.2%) achieved the primary endpoint. 61.0% and 65.1% achieved ≥ 50% reduction in MMDs at Months 3 and 6, respectively; 79.9% and 81.0% experienced ≥ 50% reduction in MIDAS at the same timepoints. CONCLUSION: Fremanezumab was effective and well-tolerated over the first 6 months of treatment, with approximately 80% of patients meeting Italian criteria for treatment continuation at Months 3 and 6.

Monoclonal antibodies targeting the calcitonin gene-related peptide pathway improve the effectiveness of acute medication-a real-world study.

BACKGROUND: One of the aims of migraine prevention is to improve response to acute migraine treatments. The aim of the present study was to assess whether monoclonal antibodies targeting the CGRP pathway (CGRP-mAbs) can improve the perceived efficacy of acute treatments. METHODS: We included and followed up patients with chronic or episodic migraine from the Headache Centers of Avezzano-L'Aquila and Naples treated with CGRP-mAbs from March 2021 to December 2022. All patients filled out the Migraine Treatment Optimization Questionnaire (MTOQ), the Headache Impact Test (HIT-6), and the Migraine Impact and Disability Assessment Scale (MIDAS) at baseline and 3-6 months after the start of treatment with CGRP-mAbs. RESULTS: Sixty-five patients (81.3%) completed the 6-month follow-up. Most patients were female (55, 84.6%), with a median age of 46 years (IQR 39-56). Median MTOQ score increased from 8 (interquartile range [IQR] 4-13) at baseline to 15 (IQR 11-17) at 3 months (p < 0.001) and 16 (IQR 13-17) at the 6-month follow-up (p < 0.001). Median migraine days over 90-day periods decreased from 40 (IQR 24-60) to 24 (IQR 15-30) at 3 months (p < 0.001) and to 20 (IQR 12-24) at 6 months (p < 0.001). Median monthly intake of acute medication decreased from 55 doses (IQR 29-80.5) to 24 doses (IQR 15-40) at 3 months and 18 doses (IQR 11-30) at 6 months (p < 0.001). CONCLUSIONS: We showed that 6 months of preventive treatment with CGRP-mAbs led to a significantly better effectiveness of acute treatments, paralleled by decreased monthly migraine days and acute treatment intake.

Cardiac magnetic resonance in advanced heart failure.

Heart failure (HF) is a chronic and progressive disease that often progresses to an advanced stage where conventional therapy is insufficient to relieve patients' symptoms. Despite the availability of advanced therapies such as mechanical circulatory support or heart transplantation, the complexity of defining advanced HF, which requires multiple parameters and multimodality assessment, often leads to delays in referral to dedicated specialists with the result of a worsening prognosis. In this review, we aim to explore the role of cardiac magnetic resonance (CMR) in advanced HF by showing how CMR is useful at every step in managing these patients: from diagnosis to prognostic stratification, hemodynamic evaluation, follow-up and advanced therapies such as heart transplantation. The technical challenges of scanning advanced HF patients, which often require troubleshooting of intracardiac devices and dedicated scans, will be also discussed.

Exploring the potential of multiomics liquid biopsy testing in the clinical setting of lung cancer.

The transformative role of artificial intelligence (AI) and multiomics could enhance the diagnostic and prognostic capabilities of liquid biopsy (LB) for lung cancer (LC). Despite advances, the transition from tissue biopsies to more sophisticated, non-invasive methods like LB has been impeded by challenges such as the heterogeneity of biomarkers and the low concentration of tumour-related analytes. The advent of multiomics - enabled by deep learning algorithms - offers a solution by allowing the simultaneous analysis of various analytes across multiple biological fluids, presenting a paradigm shift in cancer diagnostics. Through multi-marker, multi-analyte and multi-source approaches, this review showcases how AI and multiomics are identifying clinically valuable biomarker combinations that correlate with patients' health statuses. However, the path towards clinical implementation is fraught with challenges, including study reproducibility and lack of methodological standardization, thus necessitating urgent solutions to solve these common issues.

Two-stage total joint replacement for hip or knee septic arthritis: post-traumatic etiology and difficult-to-treat infections predict poor outcomes.

PURPOSE: Septic arthritis (SA) is a rare but significant clinical challenge in orthopedics that can impact patients' quality of life. This study aims to examine the clinical outcomes of patients undergoing two-stage total joint replacement (TJR) in hip and knee SA and analyze potential predictors of treatment failure. METHODS: A retrospective analysis was conducted using data from a prospectively collected institutional arthroplasty registry from January 1st, 2012, to January 1st, 2019. Patients with hip or knee SA who underwent a two-stage TJR and had at least two years of follow-up were included. Demographic characteristics, surgical variables, and outcomes were collected and analyzed from clinical and surgical data. Statistical analysis was performed using IBM SPSS Statistics, with statistical significance at p < 0.05. RESULTS: One hundred and fourteen patients (61 with hip SA, 53 with knee SA) were included in the study. The mean follow-up was 72.8 months. Postoperatively, both clinical and functional outcomes significantly improved, as indicated by the Hip Society Score (HHS) and Knee Society Score (KSS). The overall success rate of the two-stage protocol was 89.5%. Complications that did not require revision occurred in 21% of cases. The most identified pathogen was methicillin-sensitive Staphylococcus aureus (MSSA). Difficult-to-treat (DTT) infections and post-traumatic etiology were identified as predictors of treatment failure in patients undergoing two-stage TJR for hip and knee SA. CONCLUSIONS: Two-stage TJR in hip and knee SA demonstrated favorable clinical outcomes at mid-term follow-up. The procedure significantly improved functional scores and achieved a high success rate, while DTT infections and post-traumatic etiology were associated with a higher risk of treatment failure.

Cardiac Magnetic Resonance and Cardiac Implantable Electronic Devices: Are They Truly Still "Enemies"?

The application of cardiac magnetic resonance (CMR) imaging in clinical practice has grown due to technological advancements and expanded clinical indications, highlighting its superior capabilities when compared to echocardiography for the assessment of myocardial tissue. Similarly, the utilization of implantable cardiac electronic devices (CIEDs) has significantly increased in cardiac arrhythmia management, and the requirements of CMR examinations in patients with CIEDs has become more common. However, this type of exam often presents challenges due to safety concerns and image artifacts. Until a few years ago, the presence of CIED was considered an absolute contraindication to CMR. To address these challenges, various technical improvements in CIED technology, like the reduction of the ferromagnetic components, and in CMR examinations, such as the introduction of new sequences, have been developed. Moreover, a rigorous protocol involving multidisciplinary collaboration is recommended for safe CMR examinations in patients with CIEDs, emphasizing risk assessment, careful monitoring during CMR, and post-scan device evaluation. Alternative methods to CMR, such as computed tomography coronary angiography with tissue characterization techniques like dual-energy and photon-counting, offer alternative potential solutions, although their diagnostic accuracy and availability do limit their use. Despite technological advancements, close collaboration and specialized staff training remain crucial for obtaining safe diagnostic CMR images in patients with CIEDs, thus justifying the presence of specialized centers that are equipped to handle these type of exams.

A Novel Approach to Cardiac Magnetic Resonance Scar Characterization in Patients Affected by Cardiac Amyloidosis: A Pilot Study.

Background and Objectives: Cardiac magnetic resonance (CMR) imaging has become an essential instrument in the study of cardiomyopathies; it has recently been integrated into the diagnostic workflow for cardiac amyloidosis (CA) with remarkable results. An additional emerging role is the stratification of the arrhythmogenic risk by scar analysis and the possibility of merging these data with electro-anatomical maps. This is made possible by using a software (ADAS 3D, Galgo Medical, Barcelona, Spain) able to provide 3D heart models by detecting fibrosis along the whole thickness of the myocardial walls. Little is known regarding the applications of this software in the wide spectrum of cardiomyopathies and the potential benefits have yet to be discovered. In this study, we tried to apply the ADAS 3D in the context of CA. Materials and Methods: This study was a retrospectively analysis of consecutive CMR imaging of patients affected by CA that were treated in our center (Marche University Hospital). Wherever possible, the data were processed with the ADAS 3D software and analyzed for a correlation between the morphometric parameters and follow-up events. The outcome was a composite of all-cause mortality, unplanned cardiovascular hospitalizations, sustained ventricular arrhythmias (VAs), permanent reduction in left ventricular ejection fraction, and pacemaker implantation. The secondary outcomes were the need for a pacemaker implantation and sustained VAs. Results: A total of 14 patients were deemed eligible for the software analysis: 8 patients with wild type transthyretin CA, 5 with light chain CA, and 1 with transthyretin hereditary CA. The vast majority of imaging features was not related to the composite outcome, but atrial wall thickening displayed a significant association with both the primary (p = 0.003) and the secondary outcome of pacemaker implantation (p = 0.003). The software was able to differentiate between core zones and border zones of scars, with the latter being the most extensively represented in all patients. Interestingly, in a huge percentage of CMR images, the software identified the highest degree of core zone fibrosis among the epicardial layers and, in those patients, we found a higher incidence of the primary outcome, without reaching statistical significance (p = 0.18). Channels were found in the scar zones in a substantial percentage of patients without a clear correlation with follow-up events. Conclusions: CMR imaging plays a pivotal role in cardiovascular diagnostics. Our analysis shows the feasibility and applicability of such instrument for all types of CA. We could not only differentiate between different layers of scars, but we were also able to identify the presence of fibrosis channels among the different scar zones. None of the data derived from the ADAS 3D software seemed to be related to cardiac events in the follow-up, but this might be imputable to the restricted number of patients enrolled in the study.

Transcatheter Mitral Valve Intervention: Current and Future Role of Multimodality Imaging for Device Selection and Periprocedural Guidance.

Mitral regurgitation (MR) is a broadly diffuse valvular heart disease (VHD) with a significant impact on the healthcare system and patient prognosis. Transcatheter mitral valve interventions (TMVI) are now well-established techniques included in the therapeutic armamentarium for managing patients with mitral regurgitation, either primary or functional MR. Even if the guidelines give indications regarding the correct management of this VHD, the wide heterogeneity of patients' clinical backgrounds and valvular and heart anatomies make each patient a unique case, in which the appropriate device's selection requires a multimodal imaging evaluation and a multidisciplinary discussion. Proper pre-procedural evaluation plays a pivotal role in judging the feasibility of TMVI, while a cooperative work between imagers and interventionalist is also crucial for procedural success. This manuscript aims to provide an exhaustive overview of the main parameters that need to be evaluated for appropriate device selection, pre-procedural planning, intra-procedural guidance and post-operative assessment in the setting of TMVI. In addition, it tries to give some insights about future perspectives for structural cardiovascular imaging.

Estimated number of deaths attributable to NO2, PM10, and PM2.5 pollution in the Municipality of Milan in 2019.

BACKGROUND: there is growing evidence that exposure to environmental pollutants affects health, including mortality, chronic diseases, and acute diseases. The World Health Organisation has recently revised downwards the safety thresholds for exposure to environmental pollutants. The City of Milan (CoM) has particularly high levels of pollution; this is due both to the presence of various emission sources and to climatic and orographic conditions. OBJECTIVES: to describe the health effects of exposure to pollutants, measured by deaths due to environmental exposure to NO2, PM10, and PM2.5 in 2019. DESIGN: observational study. Using a pollutant concentration estimation model, annual mean values of NO2, PM10, and PM2.5 were estimated for the CoM in 2019. The number of deaths attributable to each exposure was estimated using risk functions available in the literature; the values recommended by the new World Health Organisation guidelines were used as counterfactual exposure limits. SETTING AND PARTICIPANTS: the population assisted by the Agency for Health Protection of Milan and resident in the CoM on 01.01.2019, aged 30 years or older. The place of residence was georeferenced and the population was followed up until 31.12.2019. Deaths and their causes were obtained from the Causes of Death Registry. MAIN OUTCOME MEASURES: deaths attributable to exposure from non-accidental causes, cardiovascular diseases, respiratory diseases, and lung cancer were estimated. RESULTS: in 2019, the estimated annual average level of NO2 was 36.6 µg/m3, that of PM10 was 24.9 µg/m3, and that of PM2.5 was 22.4 µg/m3, with levels varying across the city area. Concerning exposure to NO2, in 2019 10% of deaths for natural causes were estimated to be attributable to annual mean levels of NO2 above 10 µg/m3. As regard PM2.5, 13% of deaths for natural causes and 18% of deaths from lung cancer were attributable to an annual mean level above 5 µg/m3. The impact of exposure to particulate matter on mortality does not seem to be the same in all the areas of the CoM. CONCLUSIONS: the health impact of exposure to airborne particulate matter in the CoM population is high. It is important that citizens, policy-makers, and stakeholders address this issue, because of its impact on both health and healthcare costs.

[Analysis of predictive factors for non-adherence to organized screening for colorectal and breast cancers in the pre-pandemic period (2018-2019) in Lombardy Region (Northern Italy)]. / Analisi dei fattori predittivi della mancata adesione allo screening organizzato per i tumori del colon retto e della mammella nel periodo pre-pandemico (2018-2019) in Lombardia.

BACKGROUND: according to the International Agency for Cancer Research on Cancer, in 2022, breast cancer is the most common cancer in the Italian population, followed by colorectal cancer. Oncological screenings represent an effective secondary prevention strategy to counteract colorectal and breast cancers, significantly reducing mortality. In Lombardy Region (Northern Italy), screening programmes have been active since 2007, but adherence, especially in specific population subgroups, remains lower than expected. OBJECTIVES: to analyse potential predictors of non-adherence to colorectal and breast cancer screening in the Lombardy Region during the pre-pandemic period of 2018-2019. DESIGN: a retrospective cohort study aimed at investigating the role of sociodemographic variables, health status, and access to the healthcare system on non-adherence to colorectal and breast cancer screening. Statistical analyses were conducted separately by each Agency for Health Protection (ATS). The results of the models were synthesized across the Lombardy region through random-effects meta-analysis. SETTING AND PARTICIPANTS: residents within the territory of each ATS in Lombardy as of 01.01.2018 and aged between 49 and 69 years at the beginning of the follow-up. MAIN OUTCOMES MEASURES: adherence to colorectal and breast cancer screenings. RESULTS: during the study period, across the Lombardy Region, 2,820,138 individuals were eligible to participate in colorectal cancer screening, and 1,357,344 women were eligible to participate in breast cancer screening, with an invitation coverage of 87% and 86%, respectively.For breast cancer screening, older age, cardiopathy, chronic obstructive pulmonary disease (COPD), inflammatory bowel diseases (IBD), autoimmune diseases, and presence of a rare disease are associated with a reduced risk of non-adherence. Conversely, foreign citizenship, oncological diagnosis, transplant, chronic kidney disease/dialysis, diabetes, heart failure, arterial or cerebral vasculopathy, and presence of a neurological diagnosis are associated with significant excess risks of non-participation. For colorectal cancer screening, factors favouring adherence include female gender, older age, cardiopathy, COPD, autoimmune diseases, and having access/utilization of primary care. Non-adherence is associated with foreign citizenship, transplant, chronic kidney disease/dialysis, diabetes, heart failure, arterial or cerebral vasculopathy, IBD, neurological diseases, residence in assisted living facilities, use of integrated home care, and presence of disability. CONCLUSIONS: this is the first study conducted in the Lombardy Region which explores the theme of equity of access to organized screenings. This analysis highlights how sociodemographic determinants, chronic conditions, and access to the healthcare and social healthcare system constitute significant risk factors for non-adherence to screening programmes. Based on the results of this analysis, communication and/or organizational change interventions will be developed to counteract inequalities in access to effective prevention procedures.

Programmed Ventricular Stimulation as an Additional Primary Prevention Risk Stratification Tool in Arrhythmogenic Right Ventricular Cardiomyopathy: A Multinational Study.

BACKGROUND: A novel risk calculator based on clinical characteristics and noninvasive tests that predicts the onset of clinical sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been proposed and validated by recent studies. It remains unknown whether programmed ventricular stimulation (PVS) provides additional prognostic value. METHODS: All patients with a definite ARVC diagnosis, no history of sustained VAs at diagnosis, and PVS performed at baseline were extracted from 6 international ARVC registries. The calculator-predicted risk for sustained VA (sustained or implantable cardioverter defibrillator treated ventricular tachycardia [VT] or fibrillation, [aborted] sudden cardiac arrest) was assessed in all patients. Independent and combined performance of the risk calculator and PVS on sustained VA were assessed during a 5-year follow-up period. RESULTS: Two hundred eighty-eight patients (41.0±14.5 years, 55.9% male, right ventricular ejection fraction 42.5±11.1%) were enrolled. At PVS, 137 (47.6%) patients had inducible ventricular tachycardia. During a median of 5.31 [2.89-10.17] years of follow-up, 83 (60.6%) patients with a positive PVS and 37 (24.5%) with a negative PVS experienced sustained VA (P<0.001). Inducible ventricular tachycardia predicted clinical sustained VA during the 5-year follow-up and remained an independent predictor after accounting for the calculator-predicted risk (HR, 2.52 [1.58-4.02]; P<0.001). Compared with ARVC risk calculator predictions in isolation (C-statistic 0.72), addition of PVS inducibility showed improved prediction of VA events (C-statistic 0.75; log-likelihood ratio for nested models, P<0.001). PVS inducibility had a 76% [67-84] sensitivity and 68% [61-74] specificity, corresponding to log-likelihood ratios of 2.3 and 0.36 for inducible (likelihood ratio+) and noninducible (likelihood ratio-) patients, respectively. In patients with a ARVC risk calculator-predicted risk of clinical VA events <25% during 5 years (ie, low/intermediate subgroup), PVS had a 92.6% negative predictive value. CONCLUSIONS: PVS significantly improved risk stratification above and beyond the calculator-predicted risk of VA in a primary prevention cohort of patients with ARVC, mainly for patients considered to be at low and intermediate risk by the clinical risk calculator.

Clinical impact of volume of disease and time of metastatic disease presentation on patients receiving enzalutamide or abiraterone acetate plus prednisone as first-line therapy for metastatic castration-resistant prostate cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer remains a challenging condition to treat. Among the available therapeutic options, the androgen receptor signaling inhibitors abiraterone acetate plus prednisone (AA) and enzalutamide (Enza), are currently the most used first-line therapies in clinical practice. However, validated clinical indicators of prognosis in this setting are still lacking. In this study, we aimed to evaluate a prognostic model based on the time of metastatic disease presentation (after prior local therapy [PLT] or de-novo [DN]) and disease burden (low volume [LV] or high-volume [HV]) at AA/Enza onset for mCRPC patients receiving either AA or Enza as first-line. METHODS: A cohort of consecutive patients who started AA or Enza as first-line treatment for mCRPC between January 1st, 2015, and April 1st, 2019 was identified from the clinical and electronic registries of the 9 American and European participating centers. Patients were classified into 4 cohorts by the time of metastatic disease presentation (PLT or DN) and volume of disease (LV or HV; per the E3805 trial, HV was defined as the presence of visceral metastases and/or at least 4 bone metastases of which at least 1 out the axial/pelvic skeleton) at AA/Enza onset. The endpoint was overall survival defined as the time from AA or Enza initiation, respectively, to death from any cause or censored at the last follow-up visit, whichever occurred first. RESULTS: Of the 417 eligible patients identified, 157 (37.6%) had LV/PLT, 87 (20.9%) LV/DN, 64 (15.3%) HV/PLT, and 109 (26.1%) HV/DN. LV cohorts showed improved median overall survival (59.0 months; 95% CI, 51.0-66.9 months) vs. HV cohorts (27.5 months; 95% CI, 22.8-32.2 months; P = 0.0001), regardless of the time of metastatic presentation. In multivariate analysis, HV cohorts were confirmed associated with worse prognosis compared to those with LV (HV/PLT, HR = 1.87; p = 0.029; HV/DN, HR = 2.19; P = 0.002). CONCLUSION: Our analysis suggests that the volume of disease could be a prognostic factor for patients starting AA or Enza as first-line treatment for metastatic castration-resistant prostate cancer, pending prospective clinical trial validation.