Ultrasound-Guided Venous Axillary Access Versus Standard Fluoroscopic Technique for Cardiac Lead Implantation: ZEROFLUOROAXI Randomized Trial.

BACKGROUND: Axillary vein puncture (AVP) and cephalic vein surgical cutdown are recommended in international guidelines because of their low risk of pneumothorax and chronic lead complications. Directly visualizing and puncturing the axillary vein under ultrasound guidance reduces radiation exposure, provides direct needle visualization, and lowers periprocedural complications. Our hypothesis is that ultrasound-guided axillary access is safer and more feasible than the standard fluoroscopic technique. OBJECTIVES: The purpose of this study was to assess the efficacy and safety of ultrasound-guided axillary venous access during cardiac lead implantation for pacemakers (PMs) and implantable cardioverter-defibrillator (ICD) implantations. METHODS: Patients were randomized in a 1:1 fashion to either axillary venous access under fluoroscopic guidance or ultrasound-guided axillary venous access. The composite outcome, including pneumothorax, hemothorax, inadvertent arterial puncture, pocket hematoma, pocket infection, lead dislodgement, and death, was evaluated 30 days after implantation. RESULTS: We randomized 270 patients into 2 groups: the standard group for fluoroguided AVP (n = 134) and the experimental group for ultrasound-guided AVP (n = 136). No disparities in baseline characteristics were observed between the groups. The median age of the patients was 81 years, with women comprising 41% of the population. The majority of patients received single- and dual-chamber PMs (87% vs 88%; P = 1.00), and slightly over 10% in both groups received ICDs (13% vs 12%; P = 0.85). In total, we placed 357 leads in PMs and 48 leads in ICDs. Among these, 295 leads were inserted via axillary vein access and 110 via cephalic vein access. Notably, the subclavian vein was never used as a vascular access. The composite outcome was lower in the ultrasound group according to intention-to-treat analysis (OR: 0.55; 95% CI: 0.31-0.99; P = 0.034). The main difference within the composite outcome was the lower incidence of inadvertent axillary arterial puncture in the experimental group (17% vs 6%; P = 0.004). The ultrasound group also exhibited lower total procedural x-ray exposure (10,344 µGy × cm2 vs 7,119 µGy × cm2; P = 0.002) while achieving the same rate of success at the first attempt (61% vs 69%; P = 0.375). CONCLUSIONS: Ultrasound-guided AVP is safer than the fluoroscopy-guided approach because it achieves the same rate of acute success while maintaining low total procedural radiation exposure. Ultrasound AVP should be considered the optimal venous access method for cardiac lead implantation. (Ultrasound Guided Axillary Access vs Standard Fluoroscopic Technique for Cardiac Lead Implantation [ZEROFLUOROAXI]; NCT05101720).

Immune Checkpoint Inhibitors-Associated Myocarditis: Diagnosis, Treatment and Current Status on Rechallenge.

Immune checkpoint molecules like cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1), play a critical role in regulating the immune response, and immune checkpoint inhibitors (ICIs) targeting these checkpoints have shown clinical efficacy in cancer treatment; however, their use is associated with immune-related adverse events (irAEs), including cardiac complications. The prevalence of cardiac irAEs, particularly myocarditis, is relatively low, but they can become a severe and potentially life-threatening condition, usually occurring shortly after initiating ICI treatment; moreover, diagnosing ICI-related myocarditis can be challenging. Diagnostic tools include serum cardiac biomarkers, electrocardiography (ECG), echocardiography, cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB). The treatment of ICI-induced myocarditis involves high-dose corticosteroids, which have been shown to reduce the risk of major adverse cardiac events (MACE). In refractory cases, second-line immunosuppressive drugs may be considered, although their effectiveness is based on limited data. The mortality rates of ICI-induced myocarditis, particularly in severe cases, are high (38-46%). Therapy rechallenge after myocarditis is associated with a risk of recurrence and severe complications. The decision to rechallenge should be made on a case-by-case basis, involving a multidisciplinary team of cardiologists and oncologists. Further research and guidance are needed to optimize the management of cancer patients who have experienced such complications, evaluating the risks and benefits of therapy rechallenge. The purpose of this review is to summarize the available evidence on cardiovascular complications from ICI therapy, with a particular focus on myocarditis and, specifically, the rechallenge of immunotherapy after a cardiac adverse event.

The Effects of Fiscal Decentralisation on Publicly Provided Services and Labour Market.

This paper studies how fiscal decentralization affects local services. It explores a 1993 reform that increased the fiscal autonomy of Italian municipalities by replacing government transfers with revenues from a local property tax. Our identification leverages cross-municipal variation in the degree of decentralization that stems from differences in the average age of buildings caused by bombings during WWII. Decentralization reduced local spending but expanded municipal services, such as nursery schools. These effects are larger in areas with greater political competition. The paper also investigates how the reform affected labor markets. Decentralization increased female labor supply-probably through expanded availability of nursery schools- thereby reducing the gender gap in employment.

A Comparative Assessment of Myocardial Work Performance during Spontaneous Rhythm, His Bundle Pacing, and Left Bundle Branch Area Pacing: Insights from the EMPATHY Study.

BACKGROUND: Physiological pacing has gained significant interest due to its potential to achieve optimal hemodynamic response. This study aimed to assess left ventricular performance in terms of electrical parameters, specifically QRS duration and mechanical performance, evaluated as myocardial work. We compared His Bundle Pacing (HBP) and Left Bundle Branch Area Pacing (LBBAP) to evaluate their effects. METHODS: Twenty-four patients with class I or IIa indications for pacing were enrolled in this study, with twelve patients undergoing HBP implantation and another twelve undergoing LBBAP implantation. A comprehensive analysis of myocardial work was conducted. RESULTS: Our findings indicate that there were no major differences in terms of spontaneous and HBP activation in myocardial work, except for global wasted work (217 mmHg% vs. 283 mmHg%; p 0.016) and global work efficiency (87 mmHg% vs. 82 mmHg%; p 0.049). No significant differences were observed in myocardial work between spontaneous activation and LBBAP. Similarly, no significant differences in myocardial work were found between HBP and LBBAP. CONCLUSIONS: Both pacing modalities provide physiological ventricular activation without significant differences when compared to each other. Moreover, there were no significant differences in QRS duration between HBP and LBBAP. However, LBBAP demonstrated advantages in terms of feasibility, as it achieved better lead electrical parameters compared to HBP (threshold@0.4 ms 0.6 V vs. 1 V; p = 0.045-sensing 9.4 mV vs. 2.4 mV; p < 0.001). Additionally, LBBAP required less fluoroscopy time (6 min vs. 13 min; p = 0.010) and procedural time (81 min vs. 125 min; p = 0.004) compared to HBP.

Drug-based cardiovascular prevention in patients with Marfan Syndrome: a systematic review.

INTRODUCTION: Marfan Syndrome (MFS) is a rare and complex genetic disorder associated with increased aortic growth and aortic disease. The effectiveness of cardiovascular medical therapies aiming to slow down aortic growth has been tested in several trials, particularly beta-blockers and angiotensin receptor blockers, however showing conflicting results. EVIDENCE ACQUISITION: We conducted a systematic review on PubMed (Medline), Cochrane library, Google Scholar, and Biomed Central databases between January and February 2022. We selected relevant articles focusing on patients with MFS treated with beta-blockers, angiotensin receptors blockers, or both, and reporting data on the effect of the drugs on 1) slowing down aortic dilatation; 2) the reduction of aortic complication (aortic dissection, mortality, aortic surgery); and with a 3) follow-up length of at least two years. A total of 16 studies were selected. EVIDENCE SYNTHESIS: Beta-blockers remain the mainstay of therapy as they have proven to slow aortic enlargement. Angiotensin receptor blockers are a useful alternative and with proven benefit as an add-on therapy to limit aortic growth. Neither beta-blockers, nor angiotensin receptor blockers have shown meaningful results on clinical aortic endpoints. CONCLUSIONS: The current evidence of pharmacological treatment for MFS patients is conflicting due to the lack of large, randomized clinical trials with adequate follow-up studies and homogeneous age grouping. Beta-blockers and angiotensin receptor blockers are the only available treatments to reduce aortic growth. A recently published patient-level meta-analysis confirmed that angiotensin receptor blockers and beta-blockers have a similar effect on reducing the rate of increase of the aortic root Z score, used singularly or as add-on therapy. Considering the current evidence on new features related with MFS (such as mitral annular disjunction - MAD) bearing a potential additional increased arrhythmic risk, it is of paramount importance to establish the role of beta-blockers and angiotensin receptor blockers in clinical endpoints of this population as well.

The Use of Multimodality Imaging for the Diagnosis of Myocardial Outpouchings and Invaginations: A Systematic Review.

Cardiac ventricular outpouchings and invaginations are rare structural abnormalities and usually incidental findings during cardiac imaging. A definitive diagnosis is possible through the use of multimodality imaging. A systematic review of the literature was carried out in November 2022 to identify studies regarding ventricular outpouchings and invaginations. The main aim of the review is to summarize knowledge regarding epidemiology, etiology, diagnosis and prognosis of patients with ventricular outpouchings (aneurisms or diverticula) and invaginations (crypts and recesses). Overall, 26 studies published between 2000 and 2020 were included in the review. Diverticula and congenital aneurysms incidence ranges between 0.6 and 4.1%. Myocardial recesses and crypts range between 9% in the general population and up to 25% in patients with hypertrophic cardiomyopathy. The combined use of echocardiography, cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) is useful to establish tissue contractility, fibrosis, extension and relationship with adjacent structures for differential diagnosis of both invaginations and outpouchings. In conclusion, both outpouchings and invaginations are rare entities: a definitive diagnosis may be aided by the use of combining multiple imaging techniques, and the treatment depends both on the lesion-specific risk of complications and on the potential association of some lesions with cardiomyopathy.

[Clinical application and limitations of bicycle stress echocardiography (echo-bike)]. / Campi di applicazione e limiti dell'ecocardiografia da sforzo (echo-bike).

Stress echocardiography is an imaging methodology that is widely used in cardiopathic patients for the optimization of diagnosis and prognosis of patients with valvular heart diseases, in defining the response to physical stress in patients with ischemic heart disease, hypertrophic cardiomyopathy, congenital heart disease, or heart failure. However, this method is not yet sufficiently used in clinical practice. Therefore, the aim of this literature review is to describe the main fields of application of stress echocardiography with echo-bike, describing its main advantages and limitations.

The role of stress echocardiography in transcatheter aortic valve implantation and transcatheter edge-to-edge repair era: A systematic review.

Objectives: In the last decade, percutaneous treatment of valve disease has changed the approach toward the treatment of aortic stenosis (AS) and mitral regurgitation (MR). The clinical usefulness of stress echocardiography (SE) in the candidates for transcatheter aortic valve implantation (TAVI) and transcatheter edge-to-edge repair (TEER) of MR remains to be established. Therefore, the key aim of this review is to assess the main applications of SE in patients undergoing TAVI or TEER. Methods: We searched for relevant studies to be included in the systematic review on PubMed (Medline), Cochrane library, Google Scholar, and Biomed Central databases. The literature search was conducted in February 2022. The inclusion criteria of the studies were: observational and clinical trials or meta-analysis involving patients with AS or MR evaluated with SE (excluding those in which SE was used only for screening of pseudo-severe stenosis) and treated with percutaneous procedures. Results: Thirteen studies published between 2013 and 2021 were included in the review: five regarding candidates for TEER and eight for TAVI. In TEER candidates, seeing an increase in MR grade, and stroke volume of >40% during SE performed before treatment was, respectively, related to clinical benefits (p = 0.008) and an increased quality of life. Moreover, overall, 25% of patients with moderate secondary MR at rest before TEER had the worsening of MR during SE. At the same time, in SE performed after TEER, an increase in mean transvalvular diastolic gradient and in systolic pulmonary pressure is expected, but without sign and symptoms of heart failure. Regarding TAVI, several studies showed that contractile reserve (CR) is not predictive of post-TAVI ejection fraction recovery and mortality in low-flow low-gradient AS either at 30 days or at long-term. Conclusion: This systematic review shows in TEER candidates, SE has proved useful in the optimization of patient selection and treatment response, while its role in TAVI candidates is less defined. Therefore, larger trials are needed to test and confirm the utility of SE in candidates for percutaneous procedures of valve diseases.

Procalcitonin Predicts Bacterial Infection, but Not Long-Term Occurrence of Adverse Events in Patients with Acute Coronary Syndrome.

This study compiles data to determine if procalcitonin (PCT) values may predict both the risk of bacterial infection and potentially negative long-term outcomes in patients with acute coronary syndromes (ACS). All patients with a diagnosis of ACS that had PCT levels assessed during the first 24 h of hospitalization were enrolled in this study. The primary outcome was to detect the presence of bacterial infection defined as the occurrence of fever and at least one positive blood or urinary culture with clinical signs of infection. The secondary outcome was to monitor the occurrence after 1 year of the composite outcome of all-cause mortality, stroke and myocardial infarction. Overall, 569 patients were enrolled (mean age 69.37 ± 14 years, 30% females). Of these, 44 (8%) met the criteria for bacterial infection. After multivariate analysis, PCT and SBP were found to be independent predictors of bacterial infections (OR for PCT above the cut-off 2.67, 95% CI 1.09-6.53, p = 0.032 and OR for SBP 0.98, 95% CI 0.97-0.99, p = 0.043). After 1 year, the composite outcome of all-cause death, MI and stroke occurred in 104 patients (18%). PCT was not found to be an independent predictor of these outcomes. In conclusion, when assessing ACS, we found that testing for PCT levels during hospital admissions procedures was a good predictor of bacterial infections but not of all-cause mortality, stroke, or myocardial infarction. Clinicaltrial.org identifier: NCT02438085.

Assessment of the effectiveness of a novel BioFilm-Membrane BioReactor oil-polluted wastewater treatment technology by applying biomarkers in the mussel Mytilus galloprovincialis.

Petrochemical industries and oil refineries are sources of hazardous chemicals into the aquatic environments, and often a leading cause of reduced oxygen availability, thus resulting in adverse effects in biota. This study is an expansion of our previous work on the assessment of the BioFilm-Membrane Bioreactor (BF-MBR) to mitigate the impact of oil-polluted wastewater on marine environments. Specifically, this study evaluated the reduction of selected chemical constituents (hydrocarbons and trace metals) and toxicity related to hypoxia and DNA damage to mussels Mytilus galloprovincialis, before and after treatment of oil-polluted wastewater with the BF-MBR. The application of a multidisciplinary approach provided evidence of the efficiency of BF-MBR to significantly reducing the pollutants load from oily contaminated seawaters. As result, the health status of mussels was preserved by a hypoxic condition due to oily pollutants, as evidenced by the modulation in the gene expression of HIF-1α and PHD and changes in the level of hypotaurine and taurine. Moreover, ameliorative effects in the energy metabolism were also found in mussel gills showing increased levels of glycogen, glucose and ATP, as well as a mitigated genotoxicity was revealed by the Micronucleus and Comet assays. Overall, findings from this study support the use of the BF-MBR as a promising treatment biotechnology to avoid or limiting the compromise of marine environments from oil pollution.

The Dynamics and Spillovers of Management Interventions: Evidence from the Training Within Industry Program.

This paper examines the long-term and spillover effects of management interventions on firm performance. Under the Training Within Industry (TWI) program, the U.S. government provided management training to firms involved in war production between 1940 and 1945. Using a newly collected panel dataset on all 11,575 U.S. firms that applied to the program, we find that the TWI training had positive and long-lasting effects on firm performance and the adoption of beneficial managerial practices. Moreover, it generated complementarities among different types of training and had positive spillover effects on the supply chain of trained firms.

Medial pivot vs posterior stabilized total knee arthroplasty designs: a gait analysis study.

Aim To compare a medial pivot (MP) total knee arthroplasty (TKA) with posterior stabilized (PS) TKA designs from a subjective, clinical and biomechanical point of view, in a single-centre, single-surgeon, case-control non-randomized trial. Methods Sixteen patients were randomly picked up from case series into each group. Subjective outcome was assessed using the Forgotten Joint Score Questionnaire (FJSQ). Clinical evaluation included range of motion (ROM). All patients underwent gait analysis by a treadmill with force-measuring plaques and videorecording device; data were recorded for 30 seconds and included cadence, step length, stance time and walking speed. A blinded qualitative analysis of the pattern of gait was defined as biphasic or non-biphasic. Descriptive statistics for the continuous study variables and statistical significance were calculated for all parameters with independent-samples t-test and χ2 test to analyse difference in pattern of gait between groups. Results Mean FJSQ in the MP group was 91.87 (CI 95%: 88.12- 95.46) and 75.31 (CI 95%: 67.97-81.56) in the PS group (p=0.029). Mean post-operative ROM was 117° (CI 95%: 113°-122°) in the MP group and 112° (CI 95%: 108°-117°) in the PS group (p=0.14). No statistical difference was found between groups regarding all gait analysis parameters which have been recorded. Conclusion MP TKA design showed better subjective results using the FJSQ, but it did not improve significantly clinical and functional outcomes compared to PS TKA design, at a short-term follow-up.

Arthroscopic labral repair with all-suture anchors: a magnetic resonance imaging retrospective study with a 2.5-year follow-up.

Aim To evaluate radiological and clinical outcomes of a case series of patients affected by glenohumeral instability (Bankart lesion) or superior labrum tear from anterior to posterior (SLAP) lesions treated by arthroscopic repair using all-suture anchors. Methods Patients were operated by a single surgeon at a single Institution. Exclusion criteria were chondral lesions of the glenoid, rotator cuff lesions, previous surgery at the index shoulder, or a bony Bankart lesion. Position and numbers of anchors used depended on the dimension and type of lesion. The DASH (Disability of the Arm, Shoulder and Hand) and Constant scores were used for subjective and clinical evaluation at follow-ups (FUs); also, at 1-year FU, MRI scan was obtained to evaluate bone reaction to the implanted devices. Results Fifty-four patients were included. A mean of 2.7 devices per patient (145 in total) were implanted. Mean FU was 30 (range 12 - 48) months. No patient reported recurrent instability, nor hardware-related complications were registered. MRI analyses showed that 119 (82%) implants did not alter surrounding bone (grade 0), 26 (18%) implants were surrounded by bone oedema (grade 1), while no bone tunnel enlargement nor a bone cyst (grade 2 or 3, respectively) were registered. Conclusion This study confirmed the efficacy and safety of a specific all-suture anchor system in the arthroscopic repair of the glenoid labrum for glenohumeral instability or a SLAP lesion. In the short- and mid-term period, these devices were associated with good clinical and radiological outcomes without clinical failures or reaction at bone-device interface.

Cardiovascular Risks of Androgen Deprivation Therapy for Prostate Cancer.

Androgen deprivation therapy (ADT) is the gold standard treatment in patients with locally advanced or metastatic prostate cancer (PC). Emerging evidence has documented a tight association between ADT and body composition, along with metabolic profile impairment. These alterations might underpin the observed ADT-related increase in cardiovascular (CV) and thromboembolic (venous thromboembolism, VTE) mortality and morbidity. However, the specific mechanisms underlying these associations have not yet been completely elucidated. In the present review we summarize and discussed the available evidence linking ADT to increased cardio-metabolic risk, using both preclinical and clinical data. When possible, meta-analytic studies were preferred. Preclinical evidence, using a rabbit model of gonadotrophin-releasing hormone analogue-induced hypogonadism, indicates that the induced condition is associated with a dramatic increase in visceral adiposity and with an impairment of acetylcholine induced vascular relaxation, along with an increased propensity towards fatty liver. This suggests a direct role of ADT in inducing a worsened metabolic profile. In contrast, available clinical data are not sufficient to clarify a direct pathogeniclink between reduced testosterone (T) and altered metabolism. In fact, although T deprivation is associated with an altered metabolism, it is possible that the association between ADT and CV or VTE risk could simply be the result of a selection bias, related to the poor health status of patients with advanced PC. Despite the aforementioned considerations, all patients who are candidatesfor ADT should be screened for CV risk factors at baseline and monitored during the therapy. Life-style modifications and physical exercise are strongly encouraged.

Combined use of native and transplanted moss for post-mining characterization of metal(loid) river contamination.

Abandoned mine sites are a cause of great environmental concern, being potential sources of toxic elements for adjacent aquatic ecosystems with intrinsic difficulties for their management (i.e. episodic nature of pollution, technical difficulties and high costs of monitoring, remoteness). Aquatic macrophytes can find effective application in these situations, providing cost-effective data for instream water quality assessment. In this study, native and transplanted specimens of the aquatic moss Platyhypnidium riparioides were used to evaluate metal(loid) contamination in a river receiving multiple acidic and metalliferous drainages from sulphide mineralized areas and derelict mines. Analysis of native P. riparioides thalli was used to identify, in the upland course of the river, the pattern of contamination (As, Cd, Cu, Pb and Zn) which was related to the geo-environmental features of the watershed and the nearby historical mining areas. Attenuation of metal(loid) availability in the lowland river, apparently due to eco-hydrological and physic-chemical processes, was also highlighted by spatial trends of concentrations data of native and transplanted moss. The latter, deployed for 21 days at specific stretches of the river and in a tributary hydrologically connected with a dismissed mine, supported the identification of point sources (i.e. mine effluents, metallurgical waste piles amassed on the banks of the river) and the reckoning of their quantitative impact on different segments of the watercourse. By exploring multi-elemental and native-to-transplant relationships, differences in metal(loid) accumulative capacities were recognized between sampled thalli and exposed moss bags in relation to the severity of the contamination. The observed discrepancy in the accumulation of As, Fe, Ni and Pb in highly contaminated areas between native and transplanted moss of P. riparioides raises questions on the possible competing mechanisms of element uptake and retention. These findings prompt studies to discern possible limitations of the transplanting moss technique under extreme stream-quality conditions.

Assessing the Effect of Contaminated and Restored Marine Sediments in Different Experimental Mesocosms Using an Integrated Approach and Mytilus galloprovincialis as a Model.

The research presented here was conducted to ascertain the effectiveness of recovery technologies in remediating a compromised marine environment. The multidisciplinary approach aims to integrate traditional chemical-physical analysis and to assess the biological parameters of Mytilus galloprovincialis within different experimental mesocosms (W, G, and B). In particular, this system was designed to reproduce sediment resuspension in a marine environment, which is thought to be one cause of contaminant release. The study combined morphological and ultrastructural observations with DNA damage assessment and mRNA expression of those genes involved in cellular stress responses. The tissues of mussels maintained in the polluted mesocosm showed a higher accumulation of Pb and Hg than in those maintained in restored mesocosm. This observation correlates well with mRNA expression of MT10 and data on DNA damage. The outcome of the biological evaluation consolidates the chemical characterization and supports the concept that the remediation method should be evaluated at an early stage, both to analytically determine the reduction of toxic components and to assess its ultimate impact on the biological system.