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Background: Hypertension is the most prevalent cardiovascular risk factor, with several detrimental effects on the cardiovascular system. Contrasting results have been reported so far on its prognostic role in patients admitted for ST-segment elevation myocardial infarction (STEMI). Therefore, we investigated the impact of hypertension on short-term mortality in a large multicenter contemporary registry of STEMI patients, including patients treated during COVID-19 pandemic., Methods: The ISACS-STEMI COVID-19 was a retrospective registry that included STEMI patients treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 in 109 high-volume primary PCI centers from 4 continents. We collected data on baseline, clinical and procedural characteristics, in-hospital outcome and 30-day mortality. For this analysis patients were grouped according to history of hypertension at admission., Results: A total of 16083 patients were assessed, including 8813 (54.8%) with history of hypertension. These patients were more often elderly, with a worse cardiovascular risk profile, but were less frequently active smoker. Some procedural differences were observed between the two groups, including lower rate of thrombectomy and use of glycoprotein IIb/IIIa inhibitors or cangrelor but more extensive coronary disease in patients with hypertension. Between patients with and without hypertension, there was no significant difference in SARS-CoV-2 positivity. Hypertensive patients had a significantly higher in-hospital and 30-day mortality, similarly observed in both pre-COVID-19 and COVID-19 era, and confirmed after adjustment for main baseline differences and propensity score (in-hospital mortality: adjusted odds ratio (OR) [95% confidence interval (CI)] =1.673 [1.389-2.014], P  < 0.001; 30-day mortality: adjusted hazard ratio (HR) [95% CI] = 1.418 [1.230-1.636], P  < 0.001)., Conclusion: This is one of the largest and contemporary study assessing the impact of hypertension in STEMI patients undergoing primary angioplasty, including also the COVID-19 pandemic period. Hypertension was independently associated with significantly higher rates of in-hospital and 30-day mortality., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Progressive supranuclear palsy (PSP) is a neurodegenerative disease with pathological hallmarks and different clinical presentations. Recently, the Movement Disorder Society (MDS) promoted a new classification; specific combinations of the core clinical features identify different phenotypes, including PSP with Richardson's syndrome (PSP-RS) and PSP with predominant parkinsonism (PSP-P). Since speech disorders are very common in PSP, they were included in the MDS-PSP criteria as a supportive clinical feature in the form of hypokinetic, spastic dysarthria. However, little is known about how dysarthria presents across the different PSP variants. The aim of the present study is to evaluate the presence of differences in speech profile in a cohort of PSP-RS and PSP-P patients diagnosed according to the MDS-PSP criteria. Each patient underwent a neurological evaluation and perceptual and acoustic analysis of speech. Disease severity was rated using the Natural History and Neuroprotection in Parkinson plus syndromes-Parkinson plus scale (NNIPPS-PPS), including global score and sub-scores. Twenty-five patients (mean disease duration [standard deviation] = 3.32 [1.79]) were classified as PSP-RS, while sixteen as PSP-P (mean disease duration [standard deviation] = 3.47 [2.00]). These subgroups had homogeneous demographical and clinical characteristics, including disease severity quantified by the NNIPPS-PPS total score. Only the NNIPPS-PPS oculomotor function sub-score significantly differed, being more impaired in PSP-RS patients. No significant differences were found in all speech variables between the two groups. Speech evaluation is not a distinguishing feature of PSP subtypes in mid-stage disease., Competing Interests: Declarations. Compliance with ethical standards: The study was approved by the local ethics committee (protocol number: 2562, practice 69/17) and written informed consent was obtained from participants. Conflict of interest: All authors report no disclosures relevant to the manuscript., (© 2024. Fondazione Società Italiana di Neurologia.)

Affective Theory of Mind (ToM) is the ability to understand other peoples' emotional states and feelings. Several studies showed impaired affective ToM abilities in people with Parkinson's disease (PD). However, most studies tested this ability by using single-stimulus modality tasks (visual cues). The aim of the present study was to evaluate whether affective ToM abilities are impaired in PD using multiple stimulus modalities and whether they are related to disease duration and cognitive/emotional abilities. Twenty mid-stage, non-demented people with PD and 20 matched controls were evaluated by means of two tasks requiring subjects to infer others' mental states from the eyes' expression - the Reading the Mind in the Eyes (RME) test, and from the emotional prosody - a modified version of the Reading the Mind in the Voice (RMV) test. In people with PD, cognitive function and emotional processes were assessed through cognitive tasks and batteries of facial and prosodic emotion recognition tests. Compared to controls, the PD group showed significantly impaired performances in both RME and RMV tests (p < 0.0001). Affective ToM abilities in people with PD were not correlated with cognitive function or disease duration. Visual recognition of anger and auditory recognition of fear were positively correlated with RME (p = 0.0028) and RMV (p < 0.0001) test scores, respectively. Cross-modal impairment of affective ToM abilities is a non-motor feature of PD, unrelated to disease stage or cognitive status. A dysfunctional amygdala-centred network might represent the shared bases for impairments in fear and anger recognition and affective ToM abilities in PD., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest relevant to this work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Transcatheter aortic valve implantation (TAVI) has emerged as an effective and safe treatment for patients with symptomatic aortic stenosis. The indication to TAVI should be agreed upon by a Heart Team, and the procedure should be performed in centers with on-site cardiac surgery. However, TAVI complications requiring emergent cardiac surgery (ECS) have become very rare. Concurrently, access disparities and prolonged waiting times are pressing issues due to increasing clinical demand of TAVI. Many solutions have been proposed and one of them is the possibility of performing TAVI in centers without on-site cardiac surgery., Methods and Design: The Transcatheter Aortic-Valve Implantation with or without on-site Cardiac Surgery (TRACS) trial is a prospective, randomized, multicenter, open-label study with blinded adjudicated evaluation of outcomes. Patients with symptomatic severe aortic stenosis and deemed inoperable, at high surgical risk, or presenting with at least 1 clinical factor compromising the benefit/risk ratio for ECS, will be randomized to undergo TAVI either in centers with or without on-site cardiac surgery. The primary endpoint will be the composite occurrence of all-cause death, stroke, and hospital readmission for cardiovascular causes at one year. The safety endpoint will include death attributable to periprocedural complications actionable by ECS. The study aims to enroll 566 patients., Implications: The TRACS trial aims to address critical gaps in knowledge regarding the safety and efficacy of TAVI procedures performed in centers without on-site cardiac surgery, potentially improving access and outcomes for high-risk patients., Trial Registration: ClinicalTrials.gov NCT05751577., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This document aims to provide good practice recommendations in order to support maternal-foetal medicine specialists, clinical geneticists and clinical laboratory geneticists in the management of pregnancies obtained after the transfer of an embryo tested with preimplantation genetic testing (PGT). It was drafted by geneticists expert in preimplantation genetics and prenatal genetic diagnosis belonging to the "Working Group in Cytogenomics, Prenatal and Reproductive Genetics" of the "Italian Society of Human Genetics" (SIGU). In particular, the paper addresses the diagnostic algorithm to be applied in prenatal follow-up depending on the type of PGT performed, the results obtained and the related diagnostic value based on the most recent literature data and Italian and international recommendations., Competing Interests: Declarations. Conflict of interest: F.R.G. is currently a full-time employee of Menarini Silicon Biosystems (Castel Maggiore, Bologna, Italy); at the time of document conceptualization, she was an employee of TOMA Advanced Biomedical Assays S.p.A. (ImpactLab) and the coordinator of the SIGU working group of cytogenetics and cytogenomics. L.C. is employee of RDI – Italian Diagnostic Network, Cerba Healthcare Italy Group. The other authors have no conflict of interest to report related with this manuscript., (© 2024. The Author(s).)

Background: Patients with ischemic stroke (IS) or TIA face an elevated cardiovascular risk, warranting intensive lipid-lowering therapy. Despite recommendations, adherence to guidelines is suboptimal, leading to frequent undertreatment. This study aims to evaluate the statin use after IS and TIA., Methods: LIPYDS is a multicenter, observational, retrospective study including ≥ 18-year-old patients discharged after IS/TIA from 19 Italian centers in 2021. Multivariable logistic regression analysis was used to determine (1) the association between statin prescription (Any-statin versus No-statin), type (High-Intensity-statin versus Other-statin [Moderate/Low-Intensity]) with stroke etiology (TOAST), (2) clinical variables independently associated with statin prescription in the entire cohort and within TOAST categories., Results: We included 3,740 patients (median age 75 [IQR 64-82]; median LDL-C 104 [IQR 79-131]). At discharge, 1,971 (52.7%) received a High-intensity-statin, 800 (21.4%) Other-statin, 969 (25.9%) No-statin therapy. Among patients not on statin therapy before the event (N = 2686 [71.8%]), 50.1% initiated High-intensity-statin (78.2% of those with Large-Artery-Atherosclerosis, 60.8% Small-Vessel-Disease, 34.7% Cardioembolic, 47.4% Undetermined etiology); in 33% the decision to abstain from initiating statin therapy persisted. Large-Artery-Atherosclerosis showed the strongest association with Any-statin (aOR 3.07 [95%CI 2.39-3.95], p < 0.001) and High-intensity-statin (aOR 4.51 [95%CI 3.39-6.00], p < 0.001), while Cardioembolic stroke showed an inverse association (respectively, aOR 0.36 [95%CI 0.31-0.43], p < 0.001 and aOR 0.52 [95%CI 0.44-0.62], p < 0.001). Stepwise regression highlighted LDL-C and previous statin therapy as consistent predictors of statin at discharge. Older patients and women were less likely to be on a high-intensity formulation., Conclusion: Statins, especially at high-intensity, are under-prescribed after IS and TIA, with older patients, women and those with non-atherosclerotic strokes being the most affected., Competing Interests: Declarations. Conflict of interest: Andrea Zini received funding for speaker honoraria and consulting fees from Daiichi-Sankyo, Bayer, CSL Behring, Angels Initiative, Alexion-AstraZeneca, for scientific advisory board from Alexion-AstraZeneca and Bayer. Manuel Cappellari received consultancy or advisory board fees or speaker’s honoraria from Pfizer/Bristol-Meyer-Squibb, and Daiichi-Sankyo. All other co-authors have no relevant competing interests related to this study. Ethical statement: This study was approved by the local Ethical Committee (Comitato Etico Milano Area 3, n. 290-20042022)., (© 2024. Fondazione Società Italiana di Neurologia.)

Outcome data on using cangrelor in older patients are limited. This post hoc analysis of the itAlian pRospective Study on CANGrELOr (ARCANGELO) study aims to assess bleeding and ischemic outcomes with the transition from cangrelor to any oral P2Y 12 inhibitors in age-stratified subgroups (≥75 years-older, <75 years-younger) of patients with acute coronary syndrome who underwent percutaneous coronary intervention (PCI). Of 995 patients, 215 (21.6%) were older, 115 of whom (11.6%) were aged ≥80 years. Presentation with ST-elevation myocardial infarction was less frequent in older than in younger patients (52.6% vs 62.1%, p = 0.0119). At 30 days after PCI, rates of the study's primary end point of overall bleeding defined according to the Bleeding Academic Research Consortium were not significantly different between the 2 age subgroups (4.6% in the younger vs 7.4% in the older, p = 0.1179). Rates of major adverse cardiac events, defined as the composite of death, myocardial infarction, ischemia-driven revascularization, and stent thrombosis, were significantly lower in younger than in older patients (0.9% vs 3.3%, p = 0.0170). Intraprocedural thrombotic events occurring in the 48 hours after PCI arose in similar proportions in the subgroups (1.4% vs 1.4%, p = 1.000). In conclusion, these data suggest that using cangrelor with transition to any oral P2Y12 inhibitor is a safe and effective antithrombotic treatment in older patients who undergo PCI for acute coronary syndrome in the setting of routine clinical practice. Clinical Trial Registration Number: NCT04471870., Competing Interests: Declaration of competing interest Dr. Capranzano has received personal speaker fees from Daiichi Sankyo, Amgen, and Bayer. Dr. Di Mario has received research or educational grants from Abbott, Amgen, Asahi Intecc, AstraZeneca, Boston Scientific, Cardinal Health, CSL Behring, Chiesi, Daiichi Sankyo, Edwards, Medtronic, Menarini, Pfizer, Sanofi, Shockwave, Teleflex, and Volcano/Philips. Dr. De Luca has received consulting fees or honoraria from Amgen, Aspen, AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, Daiichi Sankyo, Eli Lilly, Menarini, Pfizer/Bristol‐Myers Squibb, Sanofi, Servier, and The Medicines Company, outside the present work. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

New frontiers about retinal cell transplantation for retinal degenerative diseases start from the idea that acting on stem cells can help regenerate retinal layers and establish new synapses among retinal cells. Deficiency or alterations of synaptic input and neurotrophic factors result in trans-neuronal degeneration of the inner retinal cells. Thus, the disruption of photoreceptors takes place. However, even in advanced forms of retinal degeneration, a good percentage of the ganglion cells and the inner nuclear layer neurons remain intact. This phenomenon provides evidence for obtaining retinal circuitry through the transplantation of photoreceptors into the subretinal region. The eye is regarded as an optimal organ for cell transplantation because of its immunological privilege and the relatively small number of cells collaborating to carry out visual activities. The eyeball's immunological privilege, characterized by the suppression of delayed-type hypersensitivity responses in ocular tissues, is responsible for the low rate of graft rejection in transplant patients. The main discoveries highlight the capacity of embryonic stem cells (ESCs) and induced pluripotent stem cells to regenerate damaged retinal regions. Recent progress has shown significant enhancements in transplant procedures and results. The research also explores the ethical ramifications linked to the utilization of stem cells, emphasizing the ongoing issue surrounding ESCs. The analysis centers on recent breakthroughs, including the fabrication of three-dimensional retinal organoids and the innovation of scaffolding for cell transportation. Moreover, researchers are currently assessing the possibility of CRISPR and other advanced gene editing technologies to enhance the outcomes of retinal transplantation. The widespread use of universally recognized safe surgical and imaging methods enables retinal transplantation and monitoring of transplanted cell growth toward the correct location. Currently, most therapy approaches are in the first phases of development and necessitate further research, including both pre-clinical and clinical trials, to attain favorable visual results for individuals suffering from retinal degenerative illnesses., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Endoscopic transorbital approach (eTOA) has been recently proposed as an alternative skull base approach. However, its feasibility for deeper lesions can be hampered by a reduced surgical maneuverability. Aim of this study is to consider how its extension through orbital rim resection can overcome this limitation, and to compare two different techniques for its removal., Methods: Both sides of seven cadaveric fresh frozen head were dissected. Three different surgical approaches were performed consequentially (standard eTOA, its expansion with lateral orbital rim hinge removal, and with its complete resection). Distance to target and angle of attack have been measured for superior orbital fissure (SOF), lateral wall of cavernous sinus (LWCS), anterior clinoid process (ACP), foramen rotudum (FR) and foramen ovale (FO)., Results: The angle of attack to the SOF (p = 0.01), to the LWCS (p = 0.001), to the ACP (p = 0.01), to the FR (p = 0.01) and to FO (p = 0.01) resulted larger in extended approaches with orbital rim resection, as well as the distance to target of LWCS (p = 0.04). Particularly, we observed that hinge lateral orbital rim removal improved the angle of attack to SOF (p = 0.02), APC (p = 0.01), FR (p = 0.01 and FO (p = 0.01) in comparison to the standard eTOA., Conclusion: Our study confirms that the lateral orbital rim resection could significantly expand the surgical room and the instruments maneuverability for the considered target skull base targets. Its hinge removal could balance the clinical outcome with the increase of the angles of attack for the more medial and deeper structures., Competing Interests: Declarations. Ethics approval: Ethics committee approval was waived because this study was performed in de-identified cadaveric specimens in adherence with institutional regulations governing the use of human cadaveric tissues. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Introduction: The recently published ACR/EULAR classification criteria score (3 points or more) both clinical and laboratory criteria to define the presence of antiphospholipid syndrome (APS). The clinical criteria have been better defined while laboratory criteria remain the same [lupus anticoagulant (LA), anticardiolipin (aCL) and anti ß2-Glycoprotein I (aß2GPI) antibodies] but with different impact (points) on the classification of patients. APS is excluded if more than 3 years separate positive test for antiphospholipid antibodies (aPL) and clinical manifestation., Methods: The present study evaluates how many patients would be excluded by the new criteria among those enrolled as APS in the START 2 antiphospholipid registry. The analysis includes 380 patients (274 APS and 106 carriers)., Results: Of 274 patients classified as APS, 118 (43%) did not match the new ACR/EULAR criteria for various reasons. First, the determination of aCL and aß2GPI antibodies was performed by automated instrumentations not allowed in the new criteria. Second, laboratory test score was less than 3 and this was due to an isolated IgM aCL or IgM aß2GPI in most cases and to isolated LA unconfirmed after 12 weeks in few cases. Third, 2 patients had a positive laboratory tests more than 3 years after the clinical event. Of the 106 carriers, 62% had aCL and aß2GPI determined by ELISA thus meeting the ACL/EULAR laboratory criteria but were negative for clinical criteria., Discussion: This study shows that many patients classified as APS in the START 2 registry do not match the classification using the new ACR/EULAR criteria., (© 2024 John Wiley & Sons Ltd.)

Background: Transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve (BAV) disease is still burdened by a non-negligible rate of stroke and permanent pacemaker implantation (PPI). These suboptimal results, possibly related to the unique BAV anatomy, may suggest the use of a different sizing method in this setting. The aim of our study is to evaluate whether the application of the supra-annular LIRA method may improve clinical outcomes in this population., Methods: In this single-center retrospective study, we enrolled consecutive patients with severe aortic stenosis and raphe-type BAV undergone TAVR with the implantation of supra-annular self-expanding prostheses sized according to the LIRA method. The primary endpoint was the device success. Secondary endpoints were in-hospital and 30-day safety outcomes and 1-year clinical efficacy. All study endpoints were adjudicated according to Valve Academic Research Consortium 3 criteria., Results: A total of 104 patients (mean age, 79.8 ± 5.83 years) were enrolled in our study. The mean Society of Thoracic Surgeons score was 4.96 ± 4.73%. Use of the LIRA method led to prosthesis downsizing in 85.6% of patients. Device success was 94.2%. All-cause death was 0%, conversion to surgery was 0%, and an extremely low rate of stroke (1.9%) and PPI (9.6%) was observed. The intended performance of the valve was 96.1% and it was maintained at 1-year follow-up. Clinical efficacy at 1 year was reached in 90.6% of patients., Conclusions: The LIRA method represents an alternative option for prosthesis sizing in patients with type 1 and type 2 BAV undergoing TAVR with promising early and midterm outcomes., (Copyright © 2024 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: The effectiveness of complete revascularization is well established in patients with ST-segment elevation myocardial infarction (STEMI), but it is less investigated in those with non-ST-segment elevation myocardial infarction (NSTEMI)., Objectives: This study aimed to assess whether complete revascularization, compared with culprit-only revascularization, was associated with consistent outcomes in older patients with STEMI and NSTEMI., Methods: In the FIRE (Functional Assessment in Elderly MI Patients with Multivessel Disease) trial, 1,445 older patients with myocardial infarction (MI) were randomized to culprit-only or physiology-guided complete revascularization, stratified by STEMI (n = 256 culprit-only vs n = 253 complete) and NSTEMI (n = 469 culprit-only vs n = 467 complete). The primary outcome comprised a composite of death, MI, stroke, or revascularization at 1 year. The key secondary outcome included a composite of cardiovascular death or MI at 1 year., Results: In the overall study population, physiology-guided complete revascularization reduced both primary and key secondary outcomes. The primary outcome occurred in 54 (21.1%) STEMI patients randomized to culprit-only vs 41 (16.2%) STEMI patients of the complete group (HR: 0.75; 95% CI: 0.50-1.13) and in 98 (20.9%) NSTEMI patients randomized to culprit-only vs 72 (15.4%) NSTEMI patients of the complete group (HR: 0.71; 95% CI: 0.53-0.97), with negative interaction testing (P for interaction, 0.846). Similarly, no signal of heterogeneity with respect to the initial clinical presentation was observed for the key secondary endpoint (P for interaction, 0.654)., Conclusions: Physiology-guided complete revascularization, compared with culprit-only revascularization, provided consistent benefit across the whole spectrum of patients with MI. (FIRE [Functional Assessment in Elderly MI Patients With Multivessel Disease]; NCT03772743)., Competing Interests: Funding Support and Author Disclosures Sahajanand Medical Technologies Ltd (SMT), Medis Medical Imaging Systems, Eukon S.r.l., Siemens Healthineers, General Electric (GE) Healthcare, and Insight Lifetech provided unrestricted funding to the study sponsor for the conduction of the trial. These companies had no involvement in the trial design, data collection, analysis, interpretation, or writing of the manuscript. Dr Campo has received research grants and personal fees from Abbott Vascular, GADA, Menarini, Amgen, Daichi-Sankyo, and Sanofi, outside the submitted work. Dr Moreno has received speaker/consulting fees from Abbott Vascular, AMGEN, AstraZeneca, Biosensors, Biotronik, Boston Scientific, Daiichi-Sankyo, Edwards, Medtronic, and Philips, outside the submitted work. Dr Biscaglia has received funding from the Italian Health Minister (Ricerca Finalizzata 2021, GR-2021-12372516) for the conduction of the Functional Coronary Angiography Guided Revascularization in STEMI trial; and has received personal fees from Abbott Vascular and Siemens Healthcare, outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Serum thromboxane B 2 (sTXB 2 ) is a validated biomarker of low-dose aspirin pharmacodynamics. In the original method, nonanticoagulated blood samples must be incubated at 37 °C immediately after withdrawal, centrifuged and serum supernatant should be frozen until assayed. Timely completion of all preanalytical steps may affect the feasibility and quality of sTXB 2 measurements. The storage duration of frozen serum can also affect sTXB 2 stability., Objectives: We assessed the stability of sTXB 2 in clotted blood samples stored at 4 °C before further processing and in sera stored at -40 °C for over a decade., Methods: Venous whole blood withdrawn from individuals on chronic low-dose aspirin was dispensed in different tubes and immediately incubated at 37 °C for 1 hour. The reference tube was promptly processed following the original protocol; the remaining tubes were stored at 4 °C for 12 to 72 hours before further processing. Sera stored at a controlled -40 °C temperature for <1 to 15 years were reassayed. Values within the interassay variation limits (±9%) vs baseline were considered acceptable., Results: Baseline sTXB 2 values (median, 5.4 ng/mL; IQR, 2.4-13.4 ng/mL; n  = 40) were comparable with those in samples at 4 °C up to 48 hours (median, 97% [IQR, 86%-104%] of the reference; n  = 26), but at 72 hours, the variability exceeded the interassay variation. Thromboxane B 2 levels were stable in frozen sera for up to 10 years (median, 101% [IQR, 87%-108%] of the reference; n  = 32) but decreased significantly afterward (median, 87% [IQR, 74%-109%] at 15 years; P  = .005; n  = 32)., Conclusion: Thromboxane B 2 is stable in clotted blood samples stored at 4 °C for up to 48 hours before further processing and in serum samples stored at -40 °C over 10 years., (© 2024 The Authors.)

Background: The prospective, single-arm, observational, phase 4 ETNA-AF Europe study collected real-world data about safety, effectiveness and therapeutic adherence in European patients with non-valvular atrial fibrillation newly prescribed with edoxaban and followed up for 4 years., Methods: Overall, 13 164 patients were included in the full-analysis set, which means that they had at least one documentation after baseline at 4 years. The current paper reports about the 3329 Italian patients out of the whole European population., Results: In the Italian cohort, median age was 76.0 (69.0-82.0) years, with 57.4% of the patients being ≥75 years old. The CHA2DS2-VASc score was >4 in 586 (18.1%) patients. At baseline, 670 (20.8%) patients were classified as frail by the investigators. Edoxaban 30 mg/day was prescribed to 1013 (31.8%) patients: these were older, with more comorbidities and a lower estimated creatinine clearance compared with those receiving 60 mg/day. All-cause mortality was 4.1%/year and there were very low yearly rates of bleeding and thromboembolic events: major bleeding, 0.9%; intracranial hemorrhage, 0.2%; ischemic stroke, 0.3%; systemic embolism, <0.1%. These events were more frequent in patients ≥75 years or in patients with renal impairment or treated with edoxaban 30 mg/day. Advancing age was not associated with an increased incidence of intracranial bleeding., Conclusions: These findings confirm the favorable long-term safety and effectiveness profile of edoxaban in non-valvular atrial fibrillation patients treated in routine clinical care in Italy.

Background and Aim: Diabetes has been shown in last decades to be associated with a significantly higher mortality among patients with ST-segment elevation myocardial infarction (STEMI) treated with primary PCI (PPCI). Therefore, the aim of current study was to evaluate the impact of diabetes on times delays, reperfusion and mortality in a contemporary STEMI population undergoing PPCI, including treatment during the COVID pandemic., Methods and Results: The ISACS-STEMI COVID-19 is a large-scale retrospective multicenter registry involving PPCI centers from Europe, Latin America, South-East Asia and North-Africa, including patients treated from 1st of March until June 30, 2019 and 2020. Primary study endpoint of this analysis was in-hospital mortality. Secondary endpoints were postprocedural TIMI 0-2 flow and 30-day mortality. Our population is represented by 16083 STEMI patients. A total of 3812 (23,7 %) patients suffered from diabetes. They were older, more often males as compared to non-diabetes. Diabetic patients were less often active smokers and had less often a positive family history of CAD, but they were more often affected by hypertension and hypercholesterolemia, with higher prevalence of previous STEMI and previous CABG. Diabetic patients had longer ischemia time, had more often anterior MI, cardiogenic shock, rescue PCI and multivessel disease. They had less often out-of-hospital cardiac arrest and in-stent thrombosis, received more often a mechanical support, received less often a coronary stent and DES. Diabetes was associated with a significantly impaired postprocedural TIMI flow (TIMI 0-2: 9.8 % vs 7.2 %, adjusted OR [95 % CI] = 1.17 [1.02-1.38], p = 0.024) and higher mortality (in-hospital: 9.1 % vs 4.8 %, Adjusted OR [95 % CI] = 1.70 [1.43-2.02], p < 0.001; 30-day mortality: 10.8 % vs 6 %, Adjusted HR [95 % CI] = 1.46 [1.26-1.68], p < 0.001) as compared to non-diabetes, particularly during the pandemic., Conclusions: Our study showed that in a contemporary STEMI population undergoing PPCI, diabetes is significantly associated with impaired epicardial reperfusion that translates into higher in-hospital and 30-day mortality, particularly during the pandemic., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Use of Intra-Aortic Balloon Pump (IABP) in combination with Impella has been described as an alternative strategy for mechanical circulatory support (MCS) in patients with cardiogenic shock (CS). We provide a systematic review aimed to explore the effectiveness of this paired MCS approach., Methods: We conducted a comprehensive systematic search in MEDLINE, Scopus, and Cochrane databases to identify all studies that investigated dual MCS with IABP and Impella., Results: Our search strategy identified 12 articles, including 1 randomized controlled trial, 1 retrospective study, 1 case series, 7 case report and 2 animal studies. Rationale for this combined MCS strategy stems from an observed reduction in myocardial oxygen demand/supply ratio compared to the use of each device alone, without determining significant variations in left ventricular work. Nonetheless, this combined approach also leads to a 30-40 % decline in Impella flow, increasing the risk of bleeding, Impella displacement, as well as triggering positioning and pressure alarms. Additionally, hemolytic risk data yielded inconclusive results. Importantly, there were no notable disparities in mortality rates when comparing the combined strategy to the use of each device individually., Conclusion: At the current state-of-the-art, there are no conclusive data demonstrating net clinical benefits of combining Impella with IABP. Considering the substantial risks of morbidity associated, we recommend against its use in clinical practice., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jacopo Farina reports administrative support was provided by University Hospital Arcispedale Sant'Anna of Ferrara Department of Cardiology. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: A multicenter randomized clinical trial (RCT) showed a lung recruitment maneuver using high-frequency oscillatory ventilation just before surfactant administration (ie, intubate-recruit-surfactant-extubate [IN-REC-SUR-E]) improved the efficacy of treatment compared with the standard intubate-surfactant-extubate (IN-SUR-E) technique without increasing the risk of adverse neonatal outcomes., Objective: To examine follow-up outcomes at corrected postnatal age (cPNA) 2 years of preterm infants previously enrolled in an RCT and treated with IN-REC-SUR-E or IN-SUR-E in 35 tertiary neonatal intensive care units., Design, Setting, and Participants: This was a follow-up study of infants recruited into the primary RCT from 2015 to 2018 at 35 tertiary neonatal intensive care units (NICUs) in Italy. Follow-up examinations included neurodevelopmental, growth, and respiratory outcomes of these children at cPNA 2 years. Participants included spontaneously breathing extremely preterm neonates (24 0/7 to 27 6/7 weeks' gestation) reaching failure criteria for continuous positive airway pressure within the first 24 hours of life. Data were analyzed from April 2023 to January 2024., Intervention: Infants were randomly assigned (1:1) to IN-REC-SUR-E or IN-SUR-E and then followed up., Main Outcomes and Measures: The primary outcome was the occurrence of death after discharge or major disability at cPNA 2 years. Secondary outcomes were neurodevelopmental outcomes (major disability, cerebral palsy, cognitive impairment, visual deficit, or auditory deficit), anthropometric measurements (weight, length, and head circumference), and recurrent respiratory infections and hospitalizations because of respiratory causes at 2y cPNA., Results: A total of 137 extremely preterm infants (median [IQR] gestational age, 26.5 [25.3-27.5] weeks and 75 [54.7%] female), initially enrolled in the original RCT, were followed up at cPNA 2 years, including 64 infants in the IN-SUR-E group and 73 infants in the IN-REC-SUR-E group. There were no significant differences in the occurrence of death after discharge or major disability at cPNA 2 years (IN-SUR-E: 13 children [20.3%] vs IN-REC-SUR-E: 10 children [13.7%]; P = .36). There were no significant differences in incidence of disability, cerebral palsy, or cognitive impairment in the IN-REC-SUR-E group compared with the IN-SUR-E group. There were no significant differences in anthropometric measurements (weight, length, and head circumference) between groups. There were no significant differences in the incidence of recurrent respiratory infections or in hospitalizations because of respiratory causes between groups., Conclusions and Relevance: In this RCT of lung recruitment before surfactant vs standard care there were no significant differences between the 2 groups in death, neurodevelopmental outcomes, anthropometric measurements, or recurrent respiratory infections at the 2-year follow-up. These findings can aid clinicians in decision-making for the best strategy to administer surfactant, considering long-term outcomes.

Although there is substantial evidence on the harmful effects of air pollution on human health, these are scarcely considered in the general clinical practice and also in the context of cardiovascular disease prevention. In light of the numerous epidemiological and basic research studies that have demonstrated the unfavorable impact of air pollution on the cardiovascular system, this review aims to bring this aspect to the attention of clinicians. This work describes the main air polluting components that can contribute to the onset and progression of cardiovascular diseases. The pathophysiological mechanisms underlying the impact of pollutants on the cardiovascular system and the available evidence regarding their effect on cardiovascular risk factors are reported. This article also examines the evidence relating to the correlation between environmental pollutants and some specific cardiovascular diseases, including acute coronary syndromes, cerebrovascular diseases, heart failure, and arrhythmias. Finally, the possible strategies to be implemented to limit pollution-induced cardiovascular damage are analyzed.

Background: Severe hematoma expansion (sHE) has the strongest impact on intracerebral hemorrhage (ICH) outcome. We investigated the predictors of sHE., Methods: Retrospective analysis of ICH patients admitted at nine sites in Italy, Germany, China, and Canada. The following imaging features were analyzed: non-contrast CT (NCCT) hypodensities, heterogeneous density, blend sign, irregular shape, and CT angiography (CTA) spot sign. The outcome of interest was sHE, defined as volume increase >66% and/or >12.5 from baseline to follow-up NCCT. Predictors of sHE were explored with logistic regression., Results: A total of 1472 patients were included (median age 73, 56.6% males) of whom 223 (15.2%) had sHE. Age (odds ratio (OR) per year, 95% confidence interval (CI), 1.02 (1.01-1.04)), Anticoagulant treatment (OR 3.00, 95% CI 2.09-4.31), Glasgow Coma Scale (OR 0.93, 95% CI 0.89-0.98), time from onset/last known well to imaging, (OR per h 0.96, 95% CI 0.93-0.99), and baseline ICH volume, (OR per mL 1.02, 95% CI 1.02-1.03) were independently associated with sHE. Ultra-early hematoma growth (baseline volume/baseline imaging time) was also a predictor of sHE (OR per mL/h 1.01, 95% CI 1.00-1.02). All NCCT and CTA imaging markers were also predictors of sHE. Amongst imaging features NCCT hypodensities had the highest sensitivity (0.79) whereas the CTA spot sign had the highest positive predictive value (0.51)., Conclusions: sHE is common in the natural history of ICH and can be predicted with few clinical and imaging variables. These findings might inform clinical practice and future trials targeting active bleeding in ICH., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Morotti has received expert meeting and advisory board honoraria from EMG-REG International and AstraZeneca. Dr. Shoamanesh has received speaker and consultation fees from AstraZeneca, Takeda Pharmaceuticals; and research funding from Alexion and Octapharma Canada. Dr. Paciaroni has received honoraria as a member of the speaker bureau of Sanofi-Aventis, BMS, Daiichi Sankyo, Pfizer, and iRhythm. Dr. Zini has received speaker and consultation fees from Alexion, CLS-Behring, Boehringer-Ingelheim. All the other authors report no disclosures.

Introduction: Anorexia Nervosa (AN) is a complex psychiatric illness, characterized by a high risk of developing cardiovascular complications. Given the high risk of vascular diseases in patients with AN, we can assume that patients with severe AN have a high risk of developing ischemic stroke. However, to the best of our knowledge, no reports of patients with AN presenting with ischemic stroke have been published, other than a report of the development of IS during refeeding therapy in patients with severe AN., Case Presentation: The present case report is aimed at describing the characteristics of an ischemic stroke occurring in a 19-year-old university student who had a 6-month history of AN. She was a non-smoker, had no relevant medical history and no family history of stroke. Upon hospital admission due to symptoms of stroke (aphasia and facial droop), she exhibited severe malnutrition with a BMI of 12.8 kg/m 2 . Computerized tomography imaging revealed occlusion of the left M2 branch and a congruous extensive area of hypoperfusion. Further investigations ruled out all common causes of stroke: she had no vascular stenosis, no heart diseases or arrhythmias, and no shunts, and gave negative results in autoimmune, toxicological and thrombophilia screenings., Conclusion: Clinicians should suspect development of severe complications, including ischemic stroke, in patients with severe AN. Further extensive group studies or group-based studies are needed to elucidate the etiology of ischemic stroke in patients with severe AN. This will enable us to develop more precise and effective interventions., (© 2024. The Author(s).)

Objective: The aim of this multicenter national study was to compare the outcomes of primary open surgery by aorto-bifemoral bypass (ABFB) with those performed after a failed endovascular treatment (EVT) by kissing stent technique for complex aortoiliac occlusive disease (AIOD) lesions (TransAtlantic Inter-Society Consensus [TASC] II C and D)., Methods: All consecutive ABFB cases carried out at 12 vascular surgery centers between 2016 and 2021 were retrospectively collected and analyzed. Data included patients' baseline demographics and clinical characteristics, procedural details, perioperative outcomes, and follow-up results (survival, patency, amputation). The study cohort was divided into two groups based on indications for ABFB: primary treatment vs secondary treatment after EVT failure., Results: Overall, 329 patients underwent ABFB during the study period (71% males; mean age, 64 years), of which 285 were primary treatment and 44 were after prior EVT. At baseline, no significant differences were found between study groups in demographics and clinical characteristics. TASC C and D lesions were similarly represented in the study groups (TASC C: 22% vs 78%; TASC D: 16% vs 84%). No major differences were found between study groups in terms of procedural details, early mortality, and perioperative complications. At 5 years, primary patency rates were significantly higher for primary ABFB (88%; 95% confidence interval [CI], 93.2%-84%) as compared with ABFB after prior EVT (69%; 95% CI 84.9%-55%; log rank P value < .001); however, the 5-year rates of secondary patency (100% vs 95%; 95% CI, 100%-86%) and limb salvage (97%; 95% CI, 99%-96 vs 97%; 95% CI, 100%-94%) were similar between study groups., Conclusions: Surgical treatment of TASC C/D AIOD with ABFB seems to be equally safe and effective when performed after prior EVT, although primary ABFB seemed to have higher primary patency rates. Despite the need for more frequent reinterventions, secondary patency and limb salvage rates were similar. However, future large prospective trials are required to confirm these findings., Competing Interests: Disclosures None., (Copyright © 2024. Published by Elsevier Inc.)

The consumption of energy drinks (ED) has become a growing public health issue, since potentially ED-related serious adverse cardiovascular events, including arrhythmias, myocardial infarction, cardiomyopathies, and sudden cardiac death, have been reported in recent years. The substances contained in ED include caffeine, taurine, sugars, B group vitamins and phyto-derivatives, which, especially if taken in large quantities and in a short amount of time, could cause serious side effects through various mechanisms of action, such as increased blood pressure and QT interval prolongation. Although there are still many open questions on ED that require further specific investigations, there is an urgent need for information and educational plans to the population, as well as for regulatory actions, particularly regarding transparency of substances and possible adverse effects.

Context: Data supporting successful and satisfactory penile prosthesis (PP) implantation outcomes are mainly based on subjective, rather than objective, analysis., Objective: To systematically review and objectively analyze, all available data related to patient and partner PP satisfaction., Evidence Acquisition: An extensive search was performed, including the following key-words: ("penile prosthesis" and "satisfaction"). The search, which accrued data from January 1, 1969, up to July 31, 2023, was restricted to English-language articles including human participants., Evidence Synthesis: Out of 663 retrieved articles, 83 were considered including, 12,132 subjects with a mean age and mean follow-up of 58.6 [range 20; 77.1] years and 47.6 [range 6; 374] months, respectively. Overall, a high patient satisfaction rate was observed 83[80; 86]%. The satisfaction rate increased in subjects with three-piece PP and in those with a higher rate of cardiovascular or neurological diseases and was independent of the patient's age. Partner's satisfaction rate was lower when compared to that observed in men and it increased according to the use of inflatable devices and the presence of patient Peyronie's disease. The long-term complication rate was limited ranging from 3% for erosion to 4.6% when mechanical failure was considered., Conclusions: Patient and partner satisfaction is excellent and increases with time. The number of complications is limited and is strongly associated with the presence of diabetes mellitus., Patient Summary: We found a high couple satisfaction score that was higher when reported by males compared to females. Patient satisfaction increased with time, and it was independent of age., (© 2024 American Society of Andrology and European Academy of Andrology.)

Background: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration., Methods: In this study, 382 infants born at 24 +0 -27 +6  weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24 +0 to 25 +6  weeks or 26 +0 to 27 +6  weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR)., Discussion: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24 +0 -27 +6  weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life., Trial Registration: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023., (© 2024. The Author(s).)

Aims: Tumour necrosis and/or increased mitoses define high-grade papillary thyroid carcinoma (PTC). It is unclear whether angioinvasion is prognostic for PTC. Cut-offs at five or more mitoses/2 mm 2 and four or more angioinvasive foci have been empirically defined based upon data from all forms of aggressive non-anaplastic thyroid carcinomas. Performance of tumour necrosis, mitoses and vascular invasion in predicting distant metastases when specifically applied to PTC is undefined., Methods: We analysed 50 consecutive PTC cases with distant metastases (DM-PTC): 16 synchronous and 34 metachronous. A total of 108 non-metastatic PTC (N-DM-PTC, 15.0-year median follow-up) were used as controls. Invasive encapsulated follicular variant PTC was excluded. Necrosis, mitoses and angioinvasion were quantified. Receiver operating characteristics (ROC) and area under the curve (AUC) analyses determined best sensitivity and specificity cut-offs predictive of distant metastases., Results: Metastases correlated with necrosis (any extent = 43.8% all DM-PTC, 53.1% metachronous DM-PTC versus 5% N-DM-PTC; P < 0.001), mitoses (P < 0.001) and angioinvasion (P < 0.001). Mitoses at five or more per 2 mm 2 was the best cut-off correlating with distant metastases: sensitivity/specificity 42.9%/97.2% all DM-PTC (AUC = 0.78), 18.8%/97.2% synchronous DM-PTC (AUC = 0.63), 54.6%/97.2% metachronous DM-PTC (AUC = 0.85). Angioinvasive foci at five or more was the best cut-off correlating with distant metastases: sensitivity/specificity 36.2%/91.7% all DM-PTC (AUC = 0.75), 25%/91.7% synchronous DM-PTC (AUC = 0.79) and 41.9%/91.7% metachronous DM-PTC (AUC = 0.73). Positive/negative predictive values (PPV/NPV) were: necrosis 22.6%/98.2%; five or more mitoses 32.3%/98.2%; five or more angioinvasive foci 11.8%/97.9%. After multivariable analysis, only necrosis and mitotic activity remained associated with DM-PTC., Conclusion: Our data strongly support PTC grading, statistically validating World Health Organisation (WHO) criteria to identify poor prognosis PTC. Angioinvasion is not an independent predictor of DM-PTC., (© 2024 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Background: The FIRE trial (Functional Assessment in Elderly Myocardial Infarction Patients With Multivessel Disease) enrolled 1445 older (aged ≥75 years) patients with myocardial infarction and multivessel disease in Italy, Spain, and Poland. Patients were randomized to physiology-guided complete revascularization or treatment of the only culprit lesion. Physiology-guided complete revascularization significantly reduced ischemic adverse events at 1 year. This prespecified analysis investigated the changes between the 2 study groups in angina status, quality of life, physical performance, and frailty., Methods: Patients underwent validated scales at hospital discharge (baseline) and 1 year later. Angina status was evaluated using the Seattle Angina Questionnaire, health-related quality of life by EQ visual analog scale, physical performance by short physical performance battery, and frailty by the clinical frailty scale. Mixed models for repeated measures analysis were used to study the association between the treatment arms, time, and scales., Results: Baseline and 1-year Seattle Angina Questionnaire, EQ visual analog scale, short physical performance battery, and clinical frailty scale were collected in around two-thirds of the entire FIRE study population. The mean age was 80.9±4.6 years (female sex, 35.9%). Overall, 35.3% were admitted for ST-segment-elevation myocardial infarction, whereas the others were admitted for non-ST-segment-elevation myocardial infarction. Physiology-guided complete revascularization, compared with culprit-only revascularization, was associated with greater improvement in terms of angina status (Seattle Angina Questionnaire summary score, 7.3 [95% CI, 6.1-8.6] points), health-related quality of life (EQ visual analog scale, 6.2 [95% CI, 4.4-8.1] points), and physical performance (short physical performance battery, 1.1 [95% CI, 0.9-1.3] points). After 1 year, patients randomized to culprit-only revascularization experienced a deterioration in frailty status (clinical frailty scale, 0.2 [95% CI, 0.1-0.3] points), which was not observed in patients randomized to physiology-guided complete revascularization., Conclusions: The present analysis suggested that a physiology-guided complete revascularization is associated with consistent benefits in terms of angina status, quality of life, physical performance, and the absence of further deterioration of the frailty status., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03772743., Competing Interests: Dr Campo received research grants and personal fees from Abbott Vascular and personal fees from Menarini, Amgen, and Sanofi, outside the submitted work. Dr Biscaglia received personal fees from Abbott Vascular, outside the submitted work. The other authors report no conflicts.

Background: The role of quantitative flow ratio (QFR) in the treatment of nonculprit vessels of patients with myocardial infarction (MI) is a topic of ongoing discussion., Objectives: This study aimed to investigate the predictive capability of QFR for adverse events and its noninferiority compared to wire-based functional assessment in nonculprit vessels of MI patients., Methods: The FIRE (Functional Assessment in Elderly MI Patients With Multivessel Disease) trial randomized 1,445 older MI patients to culprit-only (n = 725) or physiology-guided complete revascularization (n = 720). In the culprit-only arm, angiographic projections of nonculprit vessels were prospectively collected, centrally reviewed for QFR computation, and associated with endpoints. In the complete revascularization arm, endpoints were compared between nonculprit vessels investigated with QFR or wire-based functional assessment. The primary endpoint was the vessel-oriented composite endpoint (VOCE) at 1 year., Results: QFR was measured on 903 nonculprit vessels from 685 patients in the culprit-only arm. Overall, 366 (40.5%) nonculprit vessels showed a QFR value ≤0.80, with a significantly higher incidence of VOCEs (22.1% vs 7.1%; P < 0.001). QFR ≤0.80 emerged as an independent predictor of VOCEs (HR: 2.79; 95% CI: 1.64-4.75). In the complete arm, QFR was used in 320 (35.2%) nonculprit vessels to guide revascularization. When compared with propensity-matched nonculprit vessels in which treatment was guided by wire-based functional assessment, no significant difference was observed (HR: 0.57; 95% CI: 0.28-1.15) in VOCEs., Conclusions: This prespecified subanalysis of the FIRE trial provides evidence supporting the safety and efficacy of QFR-guided interventions for the treatment of nonculprit vessels in MI patients. (Functional Assessment in Elderly MI Patients With Multivessel Disease [FIRE]; NCT03772743)., Competing Interests: Funding Support and Author Disclosures The data supporting this paper are accessible upon reasonable request to the FIRE Study Executive Committee. Sahajanand Medical Technologies Ltd, Medis Medical Imaging Systems, Eukon S.r.l., Siemens Healthineers, General Electric Healthcare, and Insight Lifetech provided unrestricted funding to the study sponsor for the conduction of the trial. These companies had no involvement in the trial design, data collection, analysis, interpretation, or writing of the manuscript. Dr Campo has received research grants and personal fees from Abbott Vascular, GADA, Menarini, Amgen, Daichii-Sankyo, and Sanofi outside of the submitted work. Dr Moreno has received speaker/consulting fees from Abbott Vascular, AMGEN, AstraZeneca, Biosensors, Biotronik, Boston Scientific, Daiichi-Sankyo, Edwards Lifesciences, Medtronic, and Philips outside of the submitted work. Dr Barbato declares speaker fees from Abbott Vascular, Boston Scientific, Insight Lifetech, outside of the submitted work. Dr Biscaglia has received funding from the Italian Health Minister (Ricerca Finalizzata 2021, GR-2021-12372516) for the conduction of the Functional Coronary Angiography Guided Revascularization in STEMI trial; and has received personal fees from Abbott Vascular outside of the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Most intracerebral hemorrhage (ICH) trials assessed outcome at 3 months but the recovery trajectory of ICH survivors may continue up to 1 year after the index event. We aimed to describe the predictors of functional outcome improvement from 3 to 12 months after ICH., Materials and Methods: Retrospective analysis of patients admitted to six European Stroke Centers for supratentorial ICH. Functional outcome was measured with the modified Rankin Scale (mRS) at 3 and 12 months. Predictors of functional outcome improvement were explored with binary logistic regression., Results: We included 703 patients, of whom 245 (34.9%) died within 3 months. Among survivors, 131 (28.6%) had an mRS improvement, 78 (17.0%) had a worse mRS and 249 (54.4%) had a stable functional status at 12 months. Older age and the presence of baseline disability (defined as pre-stroke mRS > 1), were associated with lower odds of functional outcome improvement (Odds Ratio (OR) 0.98 per year increase, 95% Confidence Interval (CI) 0.96-1.00, p  = 0.017 and OR 0.45, 95% CI 0.25-0.81, p  = 0.008 respectively). Conversely, deep ICH location increased the probability of long term mRS improvement (OR 1.67, 95% CI, 1.07-2.61, p  = 0.023). Patients with mild-moderate disability at 3 months (mRS 2-3) had the highest odds of improvement at 12 months (OR 8.76, 95% CI 3.68-20.86, p  < 0.001)., Discussion and Conclusion: Long term recovery is common after ICH and associated with age, baseline functional status, mRS at 3 months and hematoma location. Our findings might inform future trials and improve long-term prognostication in clinical practice., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Morotti declared consulting and expert meeting honoraria for EMG-REG International and AstraZeneca. Jawed Nawabi is supported by the BIH Charité – Digital Clinician Scientist Program funded by Charité - Universitaetsmedizin Berlin, the Berlin Institute of Health and the German Research Foundation (DFG,Deutsche Forschungsgemeinschaft). Dr. Paciaroni received honoraria as a member of the speaker bureau of Sanofi-Aventis, iRhythm, Bristol Meyer Squibb, Daiiki Sankyo and Pfizer. Dr. Zini declared consulting and speaker fees from Boehringer-Ingelheim, Alexion-AstraZeneca and CSL Behring, Bayer, Angels Iniziative, Daiichi-Sankio.All the other Authors report no disclosures.

The issue of suboptimal drug regimen adherence in secondary cardiovascular prevention presents a significant barrier to improving patient outcomes. To address this, the utilization of drug combinations, specifically single pill combinations (SPCs) and polypills, was proposed as a strategy to simplify treatment regimens. This approach aims to enhance treatment accessibility, affordability, and adherence, thereby reducing healthcare costs and improving patient health. The document is an Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) scientific statement on simplifying drug regimens for secondary cardiovascular prevention. It discusses the underuse of treatments despite available, effective, and accessible options, highlighting a significant gap in secondary prevention across different socio-economic statuses and countries. The statement explores barriers to implementing evidence-based treatments, including patient, healthcare provider, and system-related challenges. The paper also reviews international guidelines, the role of SPCs and polypills in clinical practice, and their economic impact, advocating for their use in secondary prevention to improve patient outcomes and adherence., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The issue of suboptimal drug regimen adherence in secondary cardiovascular prevention presents a significant barrier to improving patient outcomes. To address this, the utilization of drug combinations, specifically single pill combinations (SPCs) and polypills, was proposed as a strategy to simplify treatment regimens. This approach aims to enhance treatment accessibility, affordability, and adherence, thereby reducing healthcare costs and improving patient health. The document is an ANMCO scientific statement on simplifying drug regimens for secondary cardiovascular prevention. It discusses the underuse of treatments despite available, effective, and accessible options, highlighting a significant gap in secondary prevention across different socioeconomic statuses and countries. The statement explores barriers to implementing evidence-based treatments, including patient, healthcare provider, and system-related challenges. The paper also reviews international guidelines, the role of SPCs and polypills in clinical practice, and their economic impact, advocating for their use in secondary prevention to improve patient outcomes and adherence.

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA., Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up., Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections., Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception., (© 2024. The Author(s).)

Background: Non-convulsive status epilepticus (NCSE) is a time-dependent neurological disorder often misdiagnosed in the emergency setting. Electroencephalography (EEG) is often not available on a 24/7 basis, and Salzburg criteria may at times miss the diagnosis. Here, we tested the accuracy of hyperperfusion on CT perfusion imaging (CTP) in the identification of NCSE against Salzburg criteria, to define its potential role in a pragmatic diagnostic workflow., Methods: We enrolled consecutive patients with suspected acute seizure or seizure disorder undergoing brain imaging with CTP and EEG from January 2021 to March 2023. EEG recordings, Salzburg criteria and CTP hyperperfusion were rated and adjudicated by two independent experts blinded to patient status. A reference standard including all clinical, lab, imaging, EEG and therapeutic data was used to adjudicate NCSE diagnosis. Sensitivity, specificity, diagnostic accuracy, positive and negative predictive values (NPV) were calculated for CTP hyperperfusion and Salzburg criteria versus NCSE adjudicated according to reference standard., Results: Seventy-seven patients were enrolled. Among 21 NCSE cases, 17 were adjudicated according to Salzburg criteria (81%) and 4 received NCSE diagnosis according to reference standard. Agreement between EEG and CTP emerged in 16/21 NCSE cases, reaching sublobar level in 37.5% of cases. Receiver operator curve analysis suggested good accuracy for CTP hyperperfusion for the diagnosis of NCSE (AUROC 0.79, 95% CI 0.69 to 0.89). CTP hyperperfusion had a high NPV for NCSE (NPV 0.97, 95% CI 0.86 to 1)., Conclusion: CTP hyperperfusion may be implemented in the emergency fast-track to rule out NCSE, given very high NPV. Further validation studies are needed to evaluate CTP application in real-world setting for NCSE codes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. STUDY REGISTRATION: This protocol was registered in clinicaltriasl.gov (NCT04282083)., (© 2024. The Author(s).)

Background: Hematoma expansion (HE) is common and predicts poor outcome in patients with supratentorial intracerebral hemorrhage (ICH). We investigated the predictors and prognostic impact of HE in infratentorial ICH., Methods: We conducted a retrospective analysis of patients with brainstem and cerebellar ICH admitted at seven sites. Noncontrast computed tomography images were analyzed for the presence of hypodensities according to validated criteria, defined as any hypodense region strictly encapsulated within the hemorrhage with any shape, size, and density. Occurrence of HE (defined as > 33% and/or > 6-mL growth) and mortality at 90 days were the outcomes of interest. Their predictors were investigated using logistic regression with backward elimination at p < 0.1. Logistic regression models for HE were adjusted for baseline ICH volume, antiplatelet and anticoagulant treatment, onset to computed tomography time, and presence of hypodensities. The logistic regression model for mortality accounted for the ICH score and HE., Results: A total of 175 patients were included (median age 75 years, 40.0% male), of whom 38 (21.7%) had HE and 43 (24.6%) died within 90 days. Study participants with HE had a higher frequency of hypodensities (44.7 vs. 24.1%, p = 0.013), presentation within 3 h from onset (39.5 vs. 24.8%, p = 0.029), and 90-day mortality (44.7 vs. 19.0%, p = 0.001). Hypodensities remained independently associated with HE after adjustment for confounders (odds ratio 2.44, 95% confidence interval 1.13-5.25, p = 0.023). The association between HE and mortality remained significant in logistic regression (odds ratio 3.68, 95% confidence interval 1.65-8.23, p = 0.001)., Conclusion: Early presentation and presence of noncontrast computed tomography hypodensities were independent predictors of HE in infratentorial ICH, and the occurrence of HE had an independent prognostic impact in this population., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Atherosclerosis is a systemic disease that can involve different arterial districts. Traditionally, the focus of cardiologists has been on the diagnosis and treatment of atherosclerotic coronary artery disease (CAD). However, atherosclerosis localization in other districts is increasingly common and is associated with an increased risk of CAD and, more generally, of adverse cardiovascular events. Although the term peripheral arterial disease (PAD) commonly refers to the localization of atherosclerotic disease in the arterial districts of the lower limbs, in this document, in accordance with the European Society of Cardiology guidelines, the term PAD will be used for all the locations of atherosclerotic disease excluding coronary and aortic ones. The aim of this review is to report updated data on PAD epidemiology, with particular attention to the prevalence and its prognostic impact on patients with CAD. Furthermore, the key points for an appropriate diagnostic framework and a correct pharmacological therapeutic approach are summarized, while surgical/interventional treatment goes beyond the scope of this review.

Introduction: Medium vessel occlusion (MeVO) accounts for 30% of acute ischemic stroke cases. The risk/benefit profile of endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT) or the combination of the two (bridging therapy (BT)) is still unclear in MeVO. Here, we compare reperfusion strategies in MeVO for clinical and radiological outcomes., Methods: This prospective single center study enrolled consecutive patients with AIS due to primary MeVO undergoing IVT, EVT, or BT at a comprehensive stroke center. Primary outcome was good functional status, defined as modified Rankin Scale (mRS) 0-2 at 3-month follow-up. Additional outcomes included mortality, successful recanalization, defined as mTICI ≥ 2b, stroke severity at discharge, and symptomatic intracerebral hemorrhage (sICH) according to SITS-MOST criteria. Logistic regression was modeled to define independent predictors of the primary outcome., Results: Overall, 180 consecutive people were enrolled (IVT = 59, EVT = 38, BT = 83), mean age 75. BT emerged as independent predictor of primary outcome (OR = 2.76, 95% CI = 1.08-7.07) together with age (OR = 0.94, 95% CI = 0.9-0.97) and baseline NIHSS (OR = 0.88, 95% CI = 0.81-0.95). BT associated with a 20% relative increase in successful recanalization compared to EVT (74.4 vs 56.4%, p = 0.049). Rates of sICH (1.1%) and procedural complications (vasospasm 4.1%, SAH in 1.7%) were very low, with no difference across groups., Discussion: BT may carry a higher chance of good functional outcome compared to EVT/IVT only in people with AIS due to MeVO, with marginally higher rates of successful recanalization. Randomized trials are needed to define optimal treatment tailoring for MeVO., (© 2023. Fondazione Società Italiana di Neurologia.)

Background: Balloon aortic valvuloplasty (BAV) is a palliative tool for patients with symptomatic severe aortic stenosis (AS) at prohibitive risk for surgery or as a bridge to surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). BAV is traditionally performed in hospitals with onsite cardiac surgery due to its potential complications., Aims: The aim of this study was to evaluate the safety of BAV procedures performed by trained high-volume operators in a centre without onsite surgery and to assess the effect of a minimalistic approach to reduce periprocedural complications., Methods: From 2016 to 2021, 187 BAV procedures were performed in 174 patients. Patients were elderly (mean age: 85.0±5.4 years) and had high-risk (mean European System for Cardiac Operative Risk Evaluation score [EuroSCORE] II: 10.1±9.9) features. According to the indications, 4 cohorts were identified: 1) bridge to TAVR (n=98; 56%); 2) bridge to SAVR (n=8; 5%); 3) cardiogenic shock (n=11; 6%); and 4) palliation (n=57; 33%). BAV procedures were performed using the standard retrograde technique via femoral access in 165 patients (95%), although radial access was used in 9 patients (5%). Ultrasound-guided vascular puncture was performed in 118 patients (72%) and left ventricular pacing was administered through a stiff guidewire in 105 cases (60%)., Results: BAV safety was confirmed by 1 periprocedural death (0.6%), 1 intraprocedural stroke (0.6%), 2 major vascular complications (1%) and 9 minor vascular complications (5%). Nine cases of in-hospital mortality occurred (5%), predominantly in patients with cardiogenic shock., Conclusions: BAV is a safe procedure that can be performed in centres without onsite cardiac surgery using a minimalistic approach that can reduce periprocedural complications., Competing Interests: The authors have no conflicts of interest to declare.

Background: The management of patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is burdened by an unfavorable prognosis even with aggressive treatment. The aim of the present study is to investigate the risk factors affecting 30-day mortality in poor-grade aSAH patients., Methods: We performed a retrospective analysis of a prospectively collected database of poor-grade aSAH patients (World Federation of Neurosurgical Societies, WFNS, grades IV and V) treated at our institution from December 2010 to December 2020. For all variables, percentages of frequency distributions were analyzed. Contingency tables (Chi-squared test) were used to assess the association between categorical variables and outcomes in the univariable analysis. Multivariable analysis was performed by using the multiple logistic regression method to estimate the odds ratio (OR) for 30-day mortality., Results: A total of 149 patients were included of which 32% had WFNS grade 4 and 68% had WFNS grade 5. The overall 1-month mortality rate was 21%. On univariable analysis, five variables were found to be associated with the likelihood of death, including intraventricular hemorrhage (IVH ≥ 50 mL, p  = 0.005), the total amount of intraventricular and intraparenchymal hemorrhage (IVH + ICH ≥ 90 mL, p  = 0.019), the IVH Ratio (IVH Ratio ≥ 40%, p  = 0.003), posterior circulation aneurysms ( p  = 0.019), presence of spot sign on initial CT scan angiography ( p  = 0.015).Nonetheless, when the multivariable analysis was performed, only IVH Ratio ( p  = 0.005; OR 3.97), posterior circulation aneurysms ( p  = 0.008; OR 4.05) and spot sign ( p  = 0.022; OR 6.87) turned out to be independent predictors of 30-day mortality., Conclusion: The risk of mortality in poor-grade aSAH remains considerable despite maximal treatment. Notwithstanding the limitations of a retrospective study, our report highlights some neuroradiological features that in the emergency setting, combined with leading clinical and anamnestic parameters, may support the multidisciplinary team in the difficult decision-making process and communication with family members from the earliest stages of poor-grade aSAH. Further prospective studies are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be taken as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Scibilia, Rustici, Linari, Zenesini, Belotti, Dall’Olio, Princiotta, Cuoci, Aspide, Migliorino, Moneti, Sturiale, Castioni, Conti, Bortolotti and Cirillo.)

Several reports describing a rare primary liver tumor with histologic features reminiscent of follicular thyroid neoplasms have been published under a variety of descriptive terms including thyroid-like, solid tubulocystic, and cholangioblastic cholangiocarcinoma. Although these tumors are considered to represent histologic variants, they lack classic features of cholangiocarcinoma and have unique characteristics, namely immunoreactivity for inhibin and NIPBL::NACC1 fusions. The purpose of this study is to present clinicopathologic and molecular data for a large series of these tumors to better understand their pathogenesis. We identified 11 hepatic tumors with these features. Immunohistochemical and NACC1 and NIPBL fluorescence in situ hybridization assays were performed on all cases. Four cases had available material for whole-genome sequencing (WGS) analysis. Most patients were adult women (mean age: 42 y) who presented with abdominal pain and large hepatic masses (mean size: 14 cm). Ten patients had no known liver disease. Of the patients with follow-up information, 3/9 (33%) pursued aggressive behavior. All tumors were composed of bland cuboidal cells with follicular and solid/trabecular growth patterns in various combinations, were immunoreactive for inhibin, showed albumin mRNA by in situ hybridization, and harbored the NIPBL::NACC1 fusion by fluorescence in situ hybridization. WGS corroborated the presence of the fusion in all 4 tested cases, high tumor mutational burden in 2 cases, and over 30 structural variants per case in 3 sequenced tumors. The cases lacked mutations typical of conventional intrahepatic cholangiocarcinoma. In this report, we describe the largest series of primary inhibin-positive hepatic neoplasms harboring a NIPBL::NACC1 fusion and the first WGS analysis of these tumors. We propose to name this neoplasm NIPBL:NACC1 fusion hepatic carcinoma., Competing Interests: Conflicts of Interest and Source of Funding: This work was supported by the Englander Institute for Precision Medicine and by the Department of Pathology and Laboratory Medicine at Weill Cornell Medicine. The work at Memorial Sloan Kettering Cancer Center was funded in part by the Marie-Josée and Henry R. Kravis Center for Molecular Oncology, the Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute under award number P30CA008748. M.F.L., J.S.M.M., and E.P. are employees at Isabl, Inc. G.G. is a consultant for Isabl. For the remaining authors none were declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Uveal melanoma (UM) is the most common primary intraocular cancer in adults. The incidence in Europe and the United States is 6-7 per million population per year. Although most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection, up to 50% of UM patients develop metastases that usually involve the liver and are fatal within 1 year. To date, chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM, which is still characterized by poor prognosis. No standard therapeutic approaches for its prevention or treatment have been established. The application of immunotherapy agents, such as immune checkpoint inhibitors that are effective in cutaneous melanoma, has shown limited effects in the treatment of ocular disease. This is due to UM's distinct genetics, natural history, and complex interaction with the immune system. Unlike cutaneous melanomas characterized mainly by BRAF or NRAS mutations, UMs are usually triggered by a mutation in GNAQ or GNA11. As a result, more effective immunotherapeutic approaches, such as cancer vaccines, adoptive cell transfer, and other new molecules are currently being studied. In this review, we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)