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•One of the most common indications for antibiotic use in the hospital setting is surgical perioperative prophylaxis.•However, limited data are available in the literature on the adherence to international and local guidelines in daily practice.•The rate of inappropriateness was high.•Being admitted to a surgical unit participating to antimicrobial stewardship program was the only factor independently related to having received appropriate prophylaxis.•A persuasive antimicrobial stewardship can significantly impact the appropriateness of surgical prophylaxis.

With nearly 700 structures solved and a growing number of customized structure prediction algorithms being developed at a fast pace, G protein-coupled receptors (GPCRs) are an optimal test case for validating new approaches for the prediction of receptor active state and ligand bioactive conformation complexes. In this study, we leveraged the availability of hundreds of peptide GPCRs in the active state and both classical homology and artificial intelligence (AI) based protein modeling combined with docking and AI-based peptide structure prediction approaches to predict the nociceptin/orphanin FQ-NOP receptor active state complex (N/OFQ-NOPa). The In Silicogenerated hypotheses were validated via the design, synthesis, and pharmacological characterization of novel linear N/OFQ(1–13)-NH2analogues, leading to the discovery of a novel antagonist (3B; pKB= 6.63) bearing a single ring-constrained residue in place of the Gly2–Gly3motif of the N/OFQ message sequence (FGGF). While the experimental validation was ongoing, the availability of the Cryo-EM structure of the predicted complex enabled us to unambiguously validate the generated hypotheses. To the best of our knowledge, this is the first example of a peptide–GPCR complex predicted with atomistic accuracy (full complex Cα RMSD < 1.0 Å) and of the N/OFQ message moiety being successfully modified with a rigid scaffold.

Fabry disease is a rare X-linked disease characterized by deficient expression and activity of alpha-galactosidase A with consequent lysosomal accumulation of glycosphingolipids, particularly globotriaosylceramide in various organs. Currently, enzyme replacement therapy with recombinant human α-galactosidase is the cornerstone of the treatment of Fabry patients, although in the long term enzyme replacement therapy fails to halt disease progression, in particular in case of late diagnosis. This suggests that the adverse outcomes cannot be justified by the lysosomal accumulation of glycosphingolipids alone, and that additional therapies targeted at further pathophysiologic mechanisms might contribute to halting the progression of cardiac, cerebrovascular and kidney disease in Fabry patients. Recent evidence points toward the involvement of oxidative stress, oxidative stress signaling and inflammation in the pathophysiology of cardio cerebrovascular and kidney damage in Fabry patients. This review reports the current knowledge of the involvement of oxidative stress in Fabry disease, which clearly points toward the involvement of oxidative stress in the pathophysiology of the medium to long-term cardio-cerebrovascular-kidney damage of Fabry patients and summarizes the antioxidant therapeutic approaches currently available in the literature. This important role played by oxidative stress suggests potential novel additional therapeutic interventions by either pharmacologic or nutritional measures, on top of enzyme replacement therapy, aimed at improving/halting the progression of cardio-cerebrovascular disease and nephropathy that occur in Fabry patients.

Achieving a high biventricular pacing percentage (BiV%) is crucial for optimizing outcomes in cardiac resynchronization therapy (CRT). The HeartLogic index, a multiparametric heart failure (HF) risk score, incorporates implantable cardioverter-defibrillator (ICD)-measured variables and has demonstrated its predictive ability for impending HF decompensation.

Abstract: A task force of the United Italian society of Endocrine Surgery (SIUEC) was commissioned to review the position statement on diagnostic, therapeutic and health‑care management protocol in parathyroid surgery published in 2014, at the light of new technologies, recent oncological concepts, and tailored approaches. The objective of this publication was to support surgeons with modern rational protocols of treatment that can be shared by health-care professionals, taking into account important clinical, healthcare and therapeutic aspects, as well as potential sequelae and complications. The task force consists of 12 members of the SIUEC highly trained and experienced in thyroid and parathyroid surgery. The main topics concern diagnostic test and localization studies, mode of admission and waiting time, therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications), hospital discharge and patient information, outpatient care and follow-up, outpatient initial management of patients with pHPT.

Brugada syndrome mainly affects young subjects with structurally normal heart and can cause x syncope or sudden death due to ventricular arrhythmias, even as the first manifestation, in approximately 5–10% of cases. To date, two questions remain open: how to recognize subjects who will experience arrhythmic events and how to treat them. The guidelines suggest treating subjects with a previous history of cardiac arrest or arrhythmogenic syncope, while they are unconclusive about the management of asymptomatic patients, who represent ∼90% of Brugada patients. We recently demonstrated that in asymptomatic patients, the presence of spontaneous Brugada type 1 electrocardiogram (ECG) pattern and inducibility of ventricular arrhythmias at electrophysiological study allows us to identify a group of patients at greater risk who deserve treatment. Regarding treatment, there are three options: implantable cardioverter defibrillator, drugs, and epicardial transcatheter ablation. Recent studies have shown that the latter is effective and free from serious side effects, thus opening a new scenario in the treatment of Brugada patients at risk. Subjects who present drug-induced-only type 1 Brugada ECG pattern, in whom a spontaneous type 1 pattern has been ruled out with repeated ECGs and 12-lead 24-h Holter monitoring, represent a very low-risk group, provided they adhere to behavioural recommendations and undergo regular follow-up.

In athletes with right bundle branch block (RBBB) morphology non-sustained ventricular arrhythmias (VAs), the presence of a non-ischaemic left ventricular scar (NLVS) may be highly suspected if one or more of the following electrocardiogram (ECG) characteristics are present at the 12-lead resting ECG: low QRS voltages in limb leads, negative Twaves in inferior leads, negative Twaves in limb leads I–aVL, negative Twaves in precordial leads V4–V6, presence of left posterior fascicular block, presence of pathologic Qwaves, and poor R-wave progression in right precordial leads. This score should be externally validated in a larger population of athletes with VAs.In athletes with RBBB morphology non-sustained Vas, attention should be placed on the 12-lead resting ECG to suspect the presence of an NLVS.In athletes with RBBB VAs and the presence of one or more of the identified ECG characteristics, a cardiac magnetic resonance with late gadolinium enhancement is useful to rule out an NLVS.Graphical Abstract

Electrocardiographic (ECG) findings in arrhythmogenic left ventricular cardiomyopathy (ALVC) are limited to small case series.

A task force of the United Italian society of Endocrine Surgery (SIUEC) was commissioned to review the position statement on diagnostic, therapeutic and health‑care management protocol in thyroid surgery published in 2016, at the light of new technologies, recent oncological concepts, and tailored approaches. The objective of this publication was to support surgeons with modern rational protocols of treatment that can be shared by health-care professionals, taking into account important clinical, healthcare and therapeutic aspects, as well as potential sequelae and complications. The task force consists of 13 members of the SIUEC highly trained and experienced in thyroid surgery. The main topics concern clinical evaluation and preoperative workup, patient preparation for surgery, surgical treatment, non-surgical options, postoperative management, prevention and management of major complications, outpatient care and follow-up.

In the present investigation, we sought to assess prevalence and clinical correlates of LQRSV in 197 consecutive HCM patients and, comparatively, in 771 Olympic athletes. Twenty-two (11%) of HCM presented LQRSV. At initial evaluation, LQRSV patients showed no differences vs. non-LQRSV for functional class (90% vs. 91%, in Classes I and II; P= 0.983), symptoms (27% vs. 18%; P= 0.478), and ventricular arrhythmias (40% vs. 39%; P= 857) but showed larger extent of LGE at CMR (4.1 ± 1.5 vs. 1.5 ± 0.7 affected segments; P< 0.001). Over 4.5 ± 2.6-year follow-up, presence of LQRSV was associated with larger incidence of functional class deterioration (31% vs. 14%; P= 0.038), stroke (22% vs. 6%; P= 0.008), and ICD implant (27% vs. 10%; P= 0.015).Eighteen (2.3%) of athletes presented LQRSV. In athletes, LQRSV was associated with larger prevalence of inverted T-waves (22% vs. 9%; P< 0.001) and ventricular arrhythmias (28% vs. 8%; P= 0.005). In one LQRSV athlete, arrhythmogenic cardiomyopathy was identified.In conclusion, LQRSV are relatively common (11%) in HCM and have clinical relevance, being predictive over a medium term for a worsening functional class, incidence of stroke, and ICD implant. Instead, LQRSV are rare (2.3%) in athletes but may be a marker that raises suspicion for underlying cardiac disease at risk.

Advances in cardiac implantable electronic devices (CIEDs) have prolonged life expectancy in various medical settings. However, the issue of hypersensitivity to components of CIEDs is still a concern. Since 1970, allergic reactions to metallic and nonmetallic components of CIEDs have been reported. Hypersensitivity reactions to medical devices are rare and not fully understood. In some cases, diagnosis and treatment are difficult. Cardiologists should always keep in mind pacemaker allergy when a patient appears with wound complications and no signs of infection. Patch testing should be tailored toward the specific biomaterials used in a device, in addition to testing with standard screening allergens in select cases. Device allergy is a rare clinical condition, probably underreported. Diagnosis and treatment can be difficult because there are no clear indications or guidelines. However, clinical suspicion should always keep in mind a device allergic reaction.

Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours.

Atrial fibrillation (AF) is a common and harmful arrhythmia. Its complex pathogenesis can be outlined using Coumel’s Triangle, that considers at the base of AF three different factors: substrate, trigger, and catalyst factor. The triangle can serve as a guide to understand the mechanism of action of the different possible treatments. Anti-arrhythmic drug therapies have a modest efficacy and no proven benefit on prognosis. Interventional therapy is more effective, especially if employed in the first stages of the disease, and can reduce mortality in selected populations. Ablative schemes must be different depending on the type of AF (paroxysmal, persistent) and the presence or absence of atrial dilation.

Implantable cardiac monitors (ICMs) have found increasing use in clinical practice over the years, proving, when used in high-risk populations, to facilitate the diagnosis of bradyarrhythmias and tachyarrhythmias requiring treatment. Experience with heart failure patients undergoing pacemaker (PMK) or implantable defibrillator (ICD) implantation, which allow for continuous electrocardiographic monitoring and transthoracic impedance assessment, has made it possible to identify predictors of heart failure flare-ups. In this context, the use of telemonitoring has been shown to ensure better management of patients with heart failure. These benefits cannot be assessed to date in patients with heart failure and left ventricular ejection fraction (LVEF) > 35% who have no indication for PMK or ICD implantation. This population has been shown to have a significant incidence of ventricular arrhythmias and bradyarrhythmias. In addition, a significant number of cerebrovascular events are observed in this population, largely attributable to the high incidence of atrial fibrillation (AF). In this population, the occurrence of AF has also been shown to have a negative impact on patients’ prognosis; at the same time, a rhythm control strategy has been shown to be more beneficial in this area than a rate control strategy. Studies also suggest arrhythmias have a negative impact on the cognitive status and quality of life of heart failure patients. These reasons could justify the implantation of ICMs equipped with telemonitoring systems in heart failure patients. The information provided by the monitoring system, if properly managed, could bring benefits in terms of prognosis and quality of life along with a reduction in economic costs. We will try here, by answering a few questions, to assess whether there is an indication for ICM in heart failure, which patients should be candidates and how these patients should be managed.

Criteria for diagnosis of arrhythmogenic cardiomyopathy (ACM) were first proposed in 1994 and subsequently revised in 2010 and in 2020 by an international task force. According to the last consensus of 2020, ACM is defined as a heart muscle disease affecting right ventricle, left ventricle or both, whose principal pathologic feature is fibrofatty myocardial replacement that impairs systolic ventricular function and predisposes to lethal ventricular arrhythmias. ECG findings not only could help to early recognize affected patients but also could identify the ones with maximum risk of ventricular arrhythmias and sudden cardiac death.

Chronic total occlusion (CTO) interventions are among the most complex procedures within the panorama of percutaneous coronary intervention (PCI). Awareness of potential complications, adequate procedural planning in order to avoid them, and prompt recognition and management should any occur are at the cornerstone of a successful CTO programme. Complications can be acute or late after the procedure and can be cardiac or non-cardiac. Acute cardiac complications can occur directly at the coronary artery level or can have other strictly non-coronary manifestations, such as hypotension, myocardial infarction, arrhythmias, or tamponade. In this review, we focus on acute coronary complications of CTO PCI, in particular their causes, prevention, and management strategies.

Patients with acute coronary syndromes (ACS) and multivessel coronary artery disease are frequently encountered during clinical practice and those patients are at higher risk of subsequent acute cardiovascular events. In patients presenting with both ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndromes, complete revascularization is associated with decreased risk of major adverse cardiovascular events. Nevertheless, the optimal timing of the intervention and treatment modality are still in discussions. Furthermore, non-culprit lesions assessment based on stenosis severity, either on visual or on functional evaluation, may not provide information about vulnerable plaques prone to thrombosis. Therefore, insights from intracoronary imaging could further identify high-risk plaque and patients at higher risk of future adverse events. This article aims to provide an overview of current guideline recommendations, envisioning future perspectives for the treatment of patients with ACS and multivessel disease.

Patients with clinically established atherosclerotic cardiovascular disease are at a very high risk of recurrent cardiovascular events. An adequate management of risk factors and the implementation of healthy behaviours significantly decrease the risk of unfavourable clinical outcomes and future cardiovascular events, including death. Patients discharged after an acute coronary syndrome should be managed according to their individual risk level in order to ensure the appropriate treatment. Nevertheless, care pathways should also take into consideration the available resources and the logistical/structural aspects. In this setting, cardiac rehabilitation is prosed as a multidisciplinary approach to improving daily function and reducing cardiovascular risk factors. The organization of a network with the involvement of different medical and non-medical figures is essential to ensure successful outcomes and expected cost-effectiveness.

The treatment of calcific coronary lesions is still a major interventional issue in haemodynamics laboratories. The prevalence of the disease is even increasing, considering the general ageing of the population undergoing coronarography, as well as the often associated comorbidities. In recent years, new devices have been developed that allow both better identification and also better treatment of these lesions. The aim of this review is to summarize both imaging modalities and dedicated techniques and materials, thus providing a kind of compendium for the treatment approach.

Heart failure (HF) is a major and still growing medical problem and is characterized by episodes of acute decompensation that are associated with a negative prognosis and a significant burden on the patients, doctors, and healthcare resources. Early detection of incipient HF may allow outpatient treatment before patients severely decompensate, thus reducing HF hospitalizations and related costs. The HeartLogic™ algorithm is an automatic, remotely managed system combining data directly related to HF pathophysiology into a single score, the HeartLogic™ index. This index proved to be effective in predicting the risk of incipient HF decompensation, allowing to redistribute resources from low-risk to high-risk patients in a timely and cost-saving manner. The alert-based remote management system seems more efficient than the one based on scheduled remote transmission in terms of caregivers’ workload and alert detection timing. The widespread application of the HeartLogic™ algorithm requires the resolution of logistical and financial issues and the adoption of a pre-defined, functional workflow. In this paper, we reviewed general aspects of remote monitoring in HF patients, the functioning and pathophysiological basis of the HeartLogic index, its efficiency in the management of HF patients, and the economic effects and the organizational revolution associated with its use.

Heart failure (HF) is one of the main causes of morbidity in the world and is responsible for an enormous amount of health costs, mostly due to hospitalizations. The remote control techniques of vital signs and health status have the potential to help prevent factors leading to HF instability by stimulating early therapeutic interventions. The goal of telemedicine is to change the intervention strategy from a ‘reactive’ type, in which therapy is optimized in response to the worsening of symptoms, to a ‘pro-active’ type, in which therapeutic changes are undertaken based on changes in the monitored parameters during the sub-clinical phase. This article is aimed at exploring the major results obtained by telemedicine application in HF patients with and without cardiac electronic devices or in those with haemodynamic sensors and to analyse the critical issues and the opportunities of its use.

The sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to reduce risks of clinical events in patients with heart failure (HF), with early and sustained benefits regardless of ejection fraction, diabetic status, and care setting. As part and parcel of the modern foundational HF therapy, clinicians should be familiar with these drugs, in order to implement their use and limit the potential adverse effects. We present an up-to-date review of current evidence and a practical guide for the prescription of SGLT2 inhibitors in patients with HF, highlighting important elements for patient selection, treatment initiation, dosing, and problem solving.

Radiofrequency (RF) catheter ablation has become a widely used therapeutic approach. However, long-term results in terms of arrhythmia recurrence are still suboptimal. Cardiac magnetic resonance (CMR) could offer a valuable tool to overcome this limitation, with the possibility of targeting the arrhythmic substrate and evaluating the location, depth, and possible gaps of RF lesions. Moreover, real-time CMR-guided procedures offer a radiation-free approach with an evaluation of anatomical structures, substrates, RF lesions, and possible complications during a single procedure. The first steps in the field have been made with cavotricuspid isthmus ablation, showing similar procedural duration and success rate to standard fluoroscopy-guided procedures, while allowing visualization of anatomic structures and RF lesions. These promising results open the path for further studies in the context of more complex arrhythmias, like atrial fibrillation and ventricular tachycardias. Of note, setting up an interventional CMR (iCMR) centre requires safety and technical standards, mostly related to the need for CMR-compatible equipment and medical staff’s educational training. For the cardiac imagers, it is fundamental to provide correct CMR sequences for catheter tracking and guide RF delivery. At the same time, the electrophysiologist needs a rapid interpretation of CMR images during the procedures. The aim of this paper is first to review the logistic and technical aspects of setting up an iCMR suite. Then, we will describe the experience in iCMR-guided flutter ablations of two European centres, Policlinico Casilino in Rome, Italy, and Haga Teaching Hospital in The Hague, the Netherlands.

Thirty years after its first description, the knowledge regarding Brugada syndrome has greatly increased. Spontaneous type 1 ECG pattern (BrECG) is a well-defined prognostic marker in asymptomatic patients and is associated with a double risk of arrhythmic events during follow-up as compared to drug-induced ECG pattern. Due to the extreme variability of the ECG pattern over time, the spontaneous type 1 BrECG must be carefully sought, not only through periodic ECGs but especially with repeated 12-lead 24-h Holter monitoring, with V1 and V2 electrodes placed also on the second and third intercostal space, in order to explore the right ventricular outflow tract. 12-lead 24-h Holter should also be performed in all the patients with a dubious BrECG pattern even before the drug challenge with sodium channel blockers, which carries a low but definite risk of complications. In addition to spontaneous type 1, other electrocardiographic markers of increased arrhythmic risk have been described, such as first-degree AV block, QRS fragmentation, S wave in lead I and II, and increased QRS duration. The electrophysiological study in asymptomatic patients with a spontaneous ECG Brugada pattern is still under jury and further studies need to clarify its precise role.

Neurocardiogenic syncope, also called vasovagal syncope, represents one of the clinical manifestations of neurally mediated syncopal syndrome. Generally, the prognosis of the cardioinhibitory form of neurocardiogenic syncope is good, but quality of life is seriously compromised in patients who experience severe forms. Drug therapy has not achieved good clinical results and very heterogeneous data come from studies regarding permanent cardiac pacing. In this scenario, the ganglionated plexi ablation has been proposed as an effective and safe method in patients with cardioinhibitory neurocardiogenic syncope, especially in young patients in order to avoid or prolong, as much as possible, the timing of definitive cardiac pacing. Certainly, making this procedure less extensive and limiting the ablation in the right atrium (avoiding the potential complications of a left atrial approach) and at level of anatomical regions of the most important ganglionated plexy, considered ‘gateway’ of the sino-atrial and atrio-ventricular node function (through the recognition of specific endocardial potentials), could be very advantageous in this clinical scenario. Finally, randomized, multicentre, clinical trials on a large population are needed to better understand which is the best ablation treatment (right-only or bi-atrial) and provide evidence for syncope guidelines.

Sudden cardiac death (SCD) can be caused by several clinical conditions, overt or misconceived, which recognize different pathophysiologies determining the development of fatal arrhythmic events. In the various forms of structural heart disease such as ischaemic heart disease, cardiomyopathies (e.g. hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic cardiomyopathy), channelopathies (e.g. long-QT syndrome, congenital short QT, Brugada syndrome, early repolarization (ER) syndrome, and idiopathic ventricular fibrillation) but also in the apparently healthy subject, the 12-lead electrocardiogram (ECG) has proved, over the years, to be a reliable and readily available method for stratifying the risk of adverse arrhythmic events and consequently SCD. Several electrocardiographic markers have been shown to be associated with adverse outcomes in different types of patients. Although with different sensitivity and specificity in each clinical condition, depolarization abnormalities, such as QRS fragmentation, Q waves, QRS duration, left posterior fascicular block, low QRS voltage, and left ventricular hypertrophy and similarly repolarization abnormalities as ER pattern, T wave alternans, QT interval, and QT dispersion, have shown significant efficacy in predicting SCD. Despite the advancement of techniques especially in the field of imaging, the correct interpretation of the 12-lead ECG remains, therefore, an effective tool for assessing the possible prognostic outcome in terms of arrhythmic risk and SCD in different types of patients.

Radiofrequency catheter ablation of the cavotricuspid isthmus is the standard treatment for patients suffering from typical atrial flutter. The aim of this study was to test the feasibility of tissue thickness and lesion transmurality measurement by a novel dielectric system. This was a retrospective multicentric non-randomized open-label, single-arm study. The atrial wall thickness was significantly higher close to the tricuspid annulus than close to the inferior vena cava and a trend towards a progressive decrease of atrial wall thickness was observed moving the mapping catheter from the tricuspid valve to the inferior vena cava. The possibility to visualize the tissue thickness could modify the way to deliver radiofrequency energy, allowing a tailored approach in cardiac ablation procedures.

The conduction system of the human heart is composed of specialized cardiomyocytes that initiate and propagate the electric impulse with consequent rhythmic and synchronized contraction of the atria and ventricles, resulting in the normal cardiac cycle. Although the His–Purkinje system (HPS) was already described more than a century ago, there has been a recent resurgence of conduction system pacing (CSP), where pacing leads are positioned in the His bundle region and left bundle branch area to provide physiological cardiac activation as alternatives to the unnatural myocardial stimulation obtained with conventional right ventricular and biventricular pacing. In this review, we describe the fundamental anatomical and pathophysiological aspects of the specialized HPS along with the CSP technique’s nuts and bolts to highlight its potential benefits in everyday clinical practice.

Stroke is a leading cause of mortality and disability, and cardiac embolism accounts for one-third of all ischaemic strokes. Thirty per cent of strokes are cryptogenic. In this setting, echocardiography is essential in the diagnosis, treatment, and prevention of embolic stroke of undetermined source since it is a widely available, safe, and inexpensive tool. Transthoracic echocardiography and transoesophageal echocardiography, furthermore, are proven to change therapeutic management leading to initiation of anti-coagulation, anti-microbial therapy, patent foramen ovale (PFO) closure, or cardiac tumour resection. The most common cardioembolic sources include left atrial appendage thrombus, left ventricular thrombus, vegetations in endocarditis, paradoxical embolization in PFO, prosthesis thrombosis, and intracardiac tumours. Although the presence of a cardioembolic source only represents a risk factor for an ischaemic stroke, it could not assure the certain or the unique cause of the event. The purpose of this review is to underline the importance of echocardiography and overview the main sources of cardiac embolism and the echocardiographic features.

Transcatheter mitral valve interventions (TMVI), either repair or replacement, are established alternative options for patients with mitral regurgitation (MR) deemed not suitable for conventional open-heart surgery. Multi-modality imaging plays a pivotal role in the selection of patients, gaining insights into the anatomy of the mitral valve the mechanism and the severity of MR, which are essential to predict the success of these procedures. The aim of this review is to provide an overview on the role of multi-modality imaging in the patient selection and pre-procedural planning of TMVI.

Fabry disease (FD) is a rare X-linked inherited lysosomal storage disorder caused by deficient a-galactosidase A activity that leads to an accumulation of glycolipids, mainly globotriaosylceramide (Gb3) and globotriaosylsphingosine, in affected tissues, including the heart. Cardiovascular involvement usually manifests as left ventricular hypertrophy (LVH), myocardial fibrosis, heart failure, and arrhythmias, which limit the quality of life and represent the most common causes of death. Following the introduction of enzyme replacement therapy, early diagnosis and treatment have become essential in slowing down the disease progression and preventing major cardiac complications. Recent advances in the understanding of FD pathophysiology suggest that in addition to Gb3 accumulation, other mechanisms contribute to the development of cardiac damage. FD cardiomyopathy is characterized by an earlier stage of glycosphingolipid accumulation and a later one of hypertrophy. Morphological and functional aspects are not specific in the echocardiographic evaluation of Anderson–Fabry disease. Cardiac magnetic resonance with tissue characterization capability is an accurate technique for the differential diagnosis of LVH. Progress in imaging techniques has improved the diagnosis and staging of FD-related cardiac disease: a decreased myocardial T1 value is specific of FD. Late gadolinium enhancement is typical of the later stage of cardiac involvement but as in other cardiomyopathy is also valuable to predict the outcome and cardiac response to therapy.

Magnetic resonance (MR) represents a new interesting imaging approach for guiding electrophysiology (EP)-based ablation procedures of atrial flutter and typical atrial fibrillation. This new approach permits to reach good results if compared with conventional EP ablation. Tissue characterization by MR permits to detect cardiac anatomy and pathological substrate like myocardial scars well visualized with late gadolinium enhancement (LGE) sequences. Intra-procedural imaging is useful to real-time follow the catheter during the ablation procedure and at the same time to visualize cardiac anatomy in addition to understanding if the ablation is correctly performed using oedema sequences. Performing cardiac ablations inside an MR room permits to reduce radiation exposure and occupational illnesses.

This article summarizes the main electrocardiogram (ECG) findings in dilated cardiomyopathy (DCM) patients. Recent reports are described in the great ‘pot’ of DCM peculiar ECG patterns that are typical of specific forms of DCM. Patients with late gadolinium enhancement on CMR, who are at greatest arrhythmic risk, have also distinctive ECG features. Future studies in large DCM populations should evaluate the diagnostic and prognostic value of the ECG.

For several years, the autonomic nervous system has played a central role in the pathophysiological mechanism of atrial fibrillation (AF), so much so that it has been considered one of the cornerstones of Coumel’s triangle. The clinical and therapeutic management of AF secondary to sympatho–vagal imbalance represents one of the most important examples of how precision medicine should be applied. Increasing knowledge of this kind of arrhythmias has made it possible to select specific antiarrhythmic drugs and to diversify their use according to vagal or adrenergic AF forms. Ablative strategies, such as cardioneuroablation and non-direct cardiac neuromodulation methods (such as renal denervation and peripheral vagal stimulation), have gradually emerged. In the possibly near future, there will be a development of new acquisitions regarding new pharmacological therapeutic strategies and gene therapy. Finally, finding an AF in patients experiencing syncopal episodes opens a whole chapter regarding interesting, but also complex, diagnostic and therapeutic strategies, ranging from neurally mediated forms to convulsive seizure that could also increase the risk of sudden death.

Chronic kidney disease (CKD) is a complex syndrome and a relevant problem of public health due to its large incidence and prevalence and to the high costs for its management. The hallmark of CKD, the progressive reduction in the glomerular filtration rate (eGFR), is strongly associated with an increase in cardiovascular events, such as fatal and non-fatal heart attack, stroke and heart failure, and mortality. Therefore, clinicians should pay any effort for preventing or slowing down the decline of renal function in order to reduce not only the occurrence of critical renal events (the need for dialysis or renal transplantation, among the most dreadful) but also the incidence of cardiovascular events. Accordingly, an early diagnosis and a targeted treatment in patients with kidney disease are crucial to reduce the evolution towards more advanced stages of the disease and the occurrence of complications. For a long time, the therapeutic approach to the majority of CKD patients was based on the strict control of risk factors, such as the diabetic disease and hypertension, together with the use of renin–angiotensin–aldosterone system inhibitors, particularly in the presence of albuminuria. Over time, this strategy proved to be only partially effective, since most CKD patients showed a progressive worsening of renal function. Gliflozins and incretins are novel anti-diabetic drugs that have been demonstrated to slow down the slope of eGFR reduction in patients with CKD, irrespective of diabetic status. Concurrently, these drugs showed to significantly impact cardiovascular prognosis reducing the incidence of clinical events. For their ability to act on a wide spectrum of disease, gliflozins and incretins are also called ‘cardio–nephro–metabolic’ drugs.

Neutrophil-to-lymphocyte ratio (NLR) is an easy-to-use inflammatory biomarker. Baseline NLR is independently associated with incident cardiovascular events and all-cause mortality. However, whether this applies to acute myocarditis (AM) has not been evaluated.

Arrhythmogenic cardiomyopathy (ACM) related to Desmoplakin (DSP) mutations is a distinct condition associated with particularly severe outcomes, more frequent left ventricular (LV) involvement including fibrosis, dysfunction and inflammatory episodes. Whether DSP-ACM is associated with specific imaging features remains elusive.

His bundle pacing (HBP) may be a challenging procedure, often involving a long fluoroscopic time (FT) and a long procedural time (PT). We sought to evaluate whether the use of a new nonfluroscopic mapping (NFM) system, the KODEX‐EPD, is able to reduce FT and PT when mapping is performed by the pacing catheter rather than an electrophysiological mapping catheter. We included 46 consecutive patients (77 ± 8 years; 63% male) who underwent HBP; in 22 a NFM‐guided procedure with the KODEX‐EPD system was performed (group 1), whereas in 24 a conventional fluoroscopy‐guided approach was used (group 2). Pacing indications were sick sinus syndrome in 13, atrioventricular block in 21, and cardiac resynchronization therapy in 12 cases. Both a lumen‐less fixed helix lead and a stylet‐driven extendable helix lead were used, respectively, in 24% and 76% of patients. HBP was successful in 22 patients (100%) in group 1 and 23 patients (96%) in group 2. The FT was significantly reduced in group 1 (183 ± 117 s vs 464.1 ± 352 s in group 2, p= .012). There were no significant differences between groups in PT and other procedural outcomes. The KODEX‐EPD system may be safely used in HBP procedures. It is effective in reducing ionizing radiation exposure, as evidenced by the significant drop in FT, without increasing PT. His bundle pacing (HBP) may be a challenging procedure, often involving a long fluoroscopic time (FT) and a long procedural time (PT). The KODEX‐EPD system may be safely used in HBP procedures. It is effective in reducing ionizing radiation exposure, as evidenced by the significant drop in FT, without increasing PT.

Background: The prevalence of certain multidrug-resistant organisms (MDROs), especially Gram-negative bacteria, is dramatically increasing in patient care settings, including pediatric and neonatal units. However, most of the new drugs available for the treatment of MDROs have not yet been studied in children and newborns. Case report: We report the clinical case of a preterm neonate, born at 31 weeks gestation + 1 day of age by emergency Cesarean Section (CS), with a bloodstream infection (BSI) due to a Verona integron-borne metallo-β-lactamase (VIM)-producing Klebsiella pneumoniae. We successfully treated the infection with cefiderocol in an off-labelregimen at the following dose: loading dose 60 mg/kg and then 40 mg/kg every 8 h in extended infusion for 9 days. The baby showed a quick clinical and biochemical improvement and tolerated well the treatment. Follow-up blood cultures at 48 h after the start of cefiderocol were negative. Conclusions: Antimicrobial-resistant pathogens are of increasing concern in neonatal settings. More studies in this unique population are necessary to better describe the pharmacokinetic and pharmacodynamic profile of the new drugs against MDROs, such as cefiderocol, and to define a proper effective dose.

Background: Parietal epithelial cells are a heterogeneous population of cells located on Bowman’s capsule. These cells are known to internalize albumin with a still undetermined mechanism, although albumin has been shown to induce phenotypic changes in parietal epithelial cells. Proximal tubular cells are the main actors in albumin handling via the macromolecular complex composed by ClC-5, megalin, and cubilin. This study investigated the role of ClC-5, megalin, and cubilin in the parietal epithelial cells of kidney biopsies from proteinuric lupus nephritis patients and control subjects and identified phenotypical changes occurring in the pathological milieu. Methods: Immunohistochemistry and immunofluorescence analyses for ClC-5, megalin, cubilin, ANXA3, podocalyxin, CD24, CD44, HSA, and LTA marker were performed on 23 kidney biopsies from patients with Lupus Nephritis and 9 control biopsies (obtained from nephrectomies for renal cancer). Results: Two sub-populations of hypertrophic parietal epithelial cells ANXA3+/Podocalyxin−/CD44−, both expressing ClC-5, megalin, and cubilin and located at the tubular pole, were identified and characterized: the first one, CD24+/HSA−/LTA−had characteristics of human adult parietal epithelial multipotent progenitors, the second one, CD24−/LTA+/HSA+committed to become phenotypically proximal tubular cells. The number of glomeruli presenting hypertrophic parietal epithelial cells positive for ClC-5, megalin, and cubilin were significantly higher in lupus nephritis patients than in controls. Conclusions: Our results may provide further insight into the role of hypertrophic parietal epithelial cells located at the tubular pole and their possible involvement in protein endocytosis in lupus nephritis patients. These data also suggest that the presence of hypertrophic parietal epithelial cells in Bowman's capsule represents a potential resource for responding to protein overload observed in other glomerulonephritis. Graphical abstract:

ABSTRACTIntroductionLurasidone is an atypical antipsychotic agent approved in the European Union for the treatment of schizophrenia in adults and adolescents (13–17 years). Clinical trials have shown a generally favorable balance between efficacy and tolerability.Areas coveredThis paper provides a review and commentary regarding the use of lurasidone in adults and adolescents with schizophrenia. The available information about efficacy, tolerability, dosing, and switching is analyzed, highlighting the strategies that may be most useful in real-world clinical practice. Virtual case studies, designed based on the authors’ clinical experience with real-world patients, are provided.Expert opinionLurasidone is efficacious in adolescents and adults in a wide range of symptoms of schizophrenia. Choosing the right dose for each patient and combining lurasidone with other medications is key to treatment success. Lurasidone has proven effective both in adolescents and adults in treating the acute phase of schizophrenia and reducing the risk of relapse. It has shown a relatively favorable tolerability profile, with minimal effects on metabolic parameters and prolactin levels.

Sleep-disordered breathing is highly prevalent in heart failure (HF) and has been suggested as a risk factor for malignant ventricular arrhythmias. The Respiratory Disturbance Index (RDI) computed by an implantable cardioverter-defibrillator (ICD) algorithm accurately identifies severe sleep apnea.