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Background In patients with active cancer and atrial fibrillation (AF) anticoagulation, thrombotic and bleeding risk still entail uncertainty. Aim We explored the results of an international survey examining the knowledge and behaviours of a large group of physicians. Methods and results A web-based survey was completed by 960 physicians (82.4% cardiologists, 75.5% from Europe). Among the currently available anticoagulants for stroke prevention in patients with active cancer, direct oral anticoagulants (DOACs) were preferred by 62.6%, with lower values for low molecular weight heparin (LMWH) (24.1%) and for warfarin (only 7.3%). About 46% of respondents considered that DOACs should be used in all types of cancers except in non-operable gastrointestinal cancers. The lack of controlled studies on bleeding risk (33.5% of respondents) and the risk of drug interactions (31.5%) were perceived as problematic issues associated with use of anticoagulants in cancer. The decision on anticoagulation involved a cardiologist in 27.8% of cases, a cardiologist and an oncologist in 41.1%, and a team approach in 21.6%. The patient also was involved in decision-making, according to ∼60% of the respondents. For risk stratification, use of CHA2DS2-VASc and HAS-BLED scores was considered appropriate, although not specifically validated in cancer patients, by 66.7% and 56.4%, respectively. Conclusion This survey highlights that management of anticoagulation in patients with AF and active cancer is challenging, with substantial heterogeneity in therapeutic choices. Direct oral anticoagulants seems having an emerging role but still the use of LMWH remains substantial, despite the absence of long-term data on thromboprophylaxis in AF.

The Council for Cardiology Practice of the European Society of Cardiology (ESC), in collaboration with the Digital Health Committee (DHC), undertook an electronic survey with 15 question multiple-choice questionnaire sent to 32 461 members of the ESC with the aim to assess the knowledge and usage of digital health (DH) technologies (DHTs) by office-based cardiologists. Of 559 respondents, 57% graded their knowledge about DH as ‘fair’ and three quarters identified the correct definition of DH. Clinical information systems, mHealth Apps, and telemedicine were the most frequently used DHTs, but 41% of respondents had concerns about their ethical and data transparency. Lack of legal clarity, low patient motivation, limited DH literacy, and poor access to DH were perceived as the main barriers to the adoption of DH. Seventy percent of the respondents were aware of the DH pages on the ESC website and 76% of the educational sessions in the DH area during the ESC Congress 2019. Only 16% had not read articles on DH. Eight-eight percent of responders declared that they would ‘probably’ or definitely attend future educational initiatives on DHT.

Although Epstein-Barr virus (EBV) is hypothesized to be a prerequisite for multiple sclerosis (MS), up to 15% of children with a diagnosis of MS were reported to be EBV-seronegative. When re-evaluating 25 EBV-seronegative children out of 189 pediatric patients with a diagnosis of clinically isolated syndrome/MS, we found anti-myelin oligodendrocyte glycoprotein (MOG) antibody in 11/25 (44%) EBV-seronegative, but only 9/164 (5.5%, p < 0.001) EBV-seropositive patients. After critical review, MS remained a plausible diagnosis in only four of 14 EBV-seronegative/MOG antibody-negative patients. In children with an MS-like presentation, EBV seronegativity should alert clinicians to consider diagnoses other than MS, especially MOG-antibody disease. This article is protected by copyright. All rights reserved.

Patent foramen ovale (PFO) and cryptogenic stroke (CS) both have a high prevalence. The optimal treatment to reduce stroke recurrence after CS remains controversial. Results from clinical trials, meta-analyses, and position papers, support percutaneous PFO device closure and medical therapy compared to medical therapy alone. However, the procedure may be associated with cardiac complications including an increased incidence of new atrial fibrillation. The benefit/risk balance should be determined on a case-by-case basis with the greatest benefit of PFO closure in patients with atrial septal aneurysm and PFO with large shunts. Future studies should address unsolved questions such as the choice of medical therapy in patients not undergoing closure, the duration of antiplatelet therapy, and the role of PFO closure in patients over 60 years old.

Serum biomarkers are an important tool in the baseline risk assessment and diagnosis of cardiovascular disease in cancer patients receiving cardiotoxic cancer treatments. Increases in cardiac biomarkers including cardiac troponin and natriuretic peptides can be used to guide initiation of cardioprotective treatments for cancer patients during treatment and to monitor the response to cardioprotective treatments, and they also offer prognostic value. This position statement examines the role of cardiac biomarkers in the management of cancer patients. The Cardio-Oncology Study Group of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the Cardio-Oncology Council of the ESC have evaluated the current evidence for the role of cardiovascular biomarkers in cancer patients before, during and after cardiotoxic cancer therapies. The characteristics of the main two biomarkers troponin and natriuretic peptides are discussed, the link to the mechanisms of cardiovascular toxicity, and the evidence for their clinical use in surveillance during and after anthracycline chemotherapy, trastuzumab and HER2-targeted therapies, vascular endothelial growth factor inhibitors, proteasome inhibitors, immune checkpoint inhibitors, cyclophosphamide and radiotherapy. Novel surveillance clinical pathways integrating cardiac biomarkers for cancer patients receiving anthracycline chemotherapy or trastuzumab biomarkers are presented and future direction in cardio-oncology biomarker research is discussed.

Cardiovascular (CV) imaging is an important tool in baseline risk assessment and detection of CV disease in oncology patients receiving cardiotoxic cancer therapies. This position statement examines the role of echocardiography, cardiac magnetic resonance, nuclear cardiac imaging and computed tomography in the management of cancer patients. The Imaging and Cardio-Oncology Study Groups of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the ESC have evaluated the current evidence for the value of modern CV imaging in the cardio-oncology field. The most relevant echocardiographic parameters, including global longitudinal strain and three-dimensional ejection fraction, are proposed. The protocol for baseline pre-treatment evaluation and specific surveillance algorithms or pathways for anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor tyrosine kinase inhibitors, BCr-Abl tyrosine kinase inhibitors, proteasome inhibitors and immune checkpoint inhibitors are presented. The indications for CV imaging after completion of oncology treatment are considered. The typical consequences of radiation therapy and the possibility of their identification in the long term are also summarized. Special populations are discussed including female survivors planning pregnancy, patients with carcinoid disease, patients with cardiac tumours and patients with right heart failure. Future directions and ongoing CV imaging research in cardio-oncology are discussed.

Background Cervical pial arteriovenous malformation (AVM) is an extremely rare condition that can present with progressive myelopathy or acute hemorrhage (subarachnoid or intramedullary). The classification process is still a topic of discussion, given the limited number of cases described, as well as correct therapeutic management. Here, we present a case of a young female with anterior cervical pial AVM associated with spinal aneurysm. Case Description A 31-year-old female in the fifth month of pregnancy presented to the emergency department for tetraparesis, sphincter disturbances, and burning dysesthesia. Through magnetic resonance angiography, a cervical pial arteriovenous malformation (AVM) with a spinal aneurysm has been diagnosed. After a multidisciplinary consult, a neurosurgical approach has been proposed to minimize the hemorrhagic risk. A laminectomy C2-C4 level was performed, followed by identification of the AVM on the anterior-lateral left-sided surface of the spinal cord. The lesion was associated with a thrombosed aneurysm at the C2 level. Using neurophysiologic monitoring, we performed a temporary clipping of afferent vessels to the AVM. The thrombosed aneurysm was removed. Indocyanine green fluorescein and intraoperative Doppler confirmed complete resolution of AVM. The postoperative course has been regular with no complications recorded. Conclusions Surgical procedure with perioperative neuromonitoring is an effective way to treat anterior cervical pial AVM associated with spinal aneurysm. A multidisciplinary approach is always suggested.

Purpose To assess the ability and reproducibility of Non-contrast Magnetic Resonance Lymphography (NMRL) in detecting and quantify lymphedema, using a semiquantitative scoring system. Methods and material This is a monocentric retrospective study of 134 consecutive patients with a clinical diagnosis of limb lymphedema who performed a Non-contrast Magnetic Resonance Lymphography (NMRL) at our Institution between November 2014 and February 2017. Lymphedema was classified based both on clinical and radiologic evaluation. An NMRL total score was obtained for each limb's segment and compared to the clinical grade, used as reference standard. NMRL intra-observer, inter-observer variability and intraclass correlation were calculated. NMRL sensitivity, specificity, and accuracy in identifying lymphedema were provided. Based on score distribution an NMRL four-stage system was developed. Results NMRL showed 92% sensitivity, 77% specificity and 82% accuracy in identifying lymphedema. An almost perfect agreement was obtained by expert operators, while substantial agreement was obtained by non-expert operators. Substantial agreement resulted also for the inter-observer variability (Cohen's Kappa K = 0.73, CI 95% [0.69–0.78]). The intra-class correlation showed an almost perfect relationship both by expert and non-expert operators. Excellent correlation between clinical grade and NMRL score and between clinical grade and NMRL stage were found for each segment. Conclusions NMRL is a confident and reproducible exam with high sensitivity, good specificity and high accuracy in lymphedema detection; the semiquantitative NMRL score resulted a reliable and reproducible tool able to quantify lymphedema severity.

Background and purpose Brain MRI-derived lesions and atrophy are related to multiple sclerosis (MS) disability. In the Serially Unified Multicenter MS Investigation (SUMMIT), from Brigham and Women's Hospital (BWH) and University of California, San Francisco (UCSF), we assessed whether MRI methodologic heterogeneity may limit the ability to pool multisite data sets to assess 5-year clinical-MRI associations. Methods Patients with relapsing-remitting (RR) MS (n = 100 from each site) underwent baseline brain MRI and baseline and 5-year clinical evaluations. Patients were matched on sex (74 women each), age, disease duration, and Expanded Disability Status Scale (EDSS) score. MRI was performed with differences between sites in both acquisition (field strength, voxel size, pulse sequences), and postprocessing pipeline to assess brain parenchymal fraction (BPF) and T2 lesion volume (T2LV). Results The UCSF cohort showed higher correlation than the BWH cohort between T2LV and disease duration. UCSF showed a higher inverse correlation between BPF and age than BWH. UCSF showed a higher inverse correlation than BWH between BPF and 5-year EDSS score. Both cohorts showed inverse correlations between BPF and T2LV, with no between-site difference. The pooled but not individual cohort data showed a link between a lower baseline BPF and the subsequent 5-year worsening in disability in addition to other stronger relationships in the data. Conclusions MRI acquisition and processing differences may result in some degree of heterogeneity in assessing brain lesion and atrophy measures in patients with MS. Pooling of data across sites is beneficial to correct for potential biases in individual data sets.

These are the clinical practice guidelines from the European Society of Cardiology on cardiovascular disease prevention in clinical practice, from 2021.

These are the clinical practice guidelines of the European Society of Cardiology on cardiac pacing and cardiac resynchronization therapy, from 2021.

Background The flow-diverter devices (FDDs) safety and effectiveness have been demonstrated by large series and meta-analyses. Due to the high occlusion rates and the acceptable morbidity rates of FDDs, the indications for their use are continuously expanding. We presented our Italian multicentric experience using the second generation of DERIVO® Embolization Device (DED®; Acandis, Pforzheim, Germany) to cure cerebral aneurysms, evaluating both middle and long-term safety and efficacy of this device. Methods Between July 2016 and September 2017 we collected 109 consecutive aneurysms in 108 patients treated using DED® during 109 endovascular procedures in 34 Italian centers (100/109 aneurysms were unruptured, 9/109 were ruptured). The collected data included patient demographics, aneurysm location and characteristics, baseline angiography, adverse event and serious adverse event information, morbidity and mortality rates, and pre- and post-treatment modified Rankin Scale scores. Midterm and long-term clinical, angiographic and cross-sectional CT/MR follow-up were recorded and collected until December 2018. Results In 2/109 cases, DED® placement was classified as technical failures. The overall mortality and morbidity rates were respectively 6.5% and 5.5%. Overall DERIVO® related mortality and morbidity rates were respectively 0% and 4.6% (5 out of 108 patients). Midterm neuroimaging follow-up showed the complete or nearly complete occlusion of the aneurysm in 90% cases, which became 93% at long-term follow-up. Aneurysmal sac shrinking was observed in 65% of assessable aneurysms. Conclusions Our multicentric experience using DED® for endovascular treatment of unruptured and ruptured aneurysms showed a high safety and efficacy profile, substantially equivalent or better compared to the other FDDs.

INTRODUCTION: A direct aspiration first pass technique (ADAPT) is an alternative technique as first-line thrombectomy for large vessel occlusion in acute ischemic stroke, still debated when compared to first-line stent retriever. To retrospectively evaluate technical and clinical outcomes of the ADAPT as first-line treatment for anterior circulation acute ischemic stroke with large-bore reperfusion catheters. METHODS: A multicentric data collection from 14 medical centers was retrospectively analyzed. Large-bore catheters had a distal diameter between 0.64 and 0.71 in; stent retriever was added when aspiration alone failed. Baseline characteristics, technical and clinical variables were collected, including NIHSS, thrombolysis in cerebral infarction (TICI), peri-procedural complications, 90-day mRS and 90-day mortality. RESULTS: Overall, 501 patients were treated. No statistically significant difference in terms of baseline features or tPA administration was recorded between patients treated with ADAPT and with additional stent retriever. ADAPT alone was successful in achieving TICI ≥ 2b in 71.8% with a median of 1.55 aspiration attempts. In terms of TICI ≥ 2b, ADAPT alone was better than additional stent retriever (p

Background and purpose Acute ischemic stroke (AIS) is a common complication of coronavirus disease 2019 (COVID‐19), but the underlying biological mechanisms remain unclear. We aimed to describe the prevalence of vessel wall alterations in patients with cryptogenic stroke through vessel wall magnetic resonance imaging (vwMRI). Methods All consecutive patients admitted for AIS and COVID‐19 to a single neuro‐COVID unit from 10 November to 31 December 2020 were prospectively evaluated and underwent a complete etiologic workup for AIS. In patients with cryptogenic stroke, the diagnostic workup was completed with vwMRI study. Results After the exclusion of four patients ineligible for MRI, a total of 10 patients were included (median age = 78 years, 50% males), of whom four (40%) had a cryptogenic stroke. vwMRI showed vascular changes consistent with inflammation of intracranial artery walls in three subjects (75%). Two patients had focal and one multifocal involvement. Conclusions vwMRI detected signs of vascular inflammation in the majority of patients with cryptogenic AIS, leading to an etiologic definition with potential therapeutical implications. Our findings are best interpreted as hypothesis‐generating, suggesting the possibility of expanding the diagnostic workup of cryptogenic stroke with vessel wall imaging., Acute ischemic stroke (AIS) is a common complication of coronavirus disease 2019 (COVID‐19), and a high frequency of cryptogenic events has been reported. In these cases, a possible underlying inflammatory etiology has been proposed. Vessel wall magnetic resonance imaging detected signs of vascular inflammation in the majority of patients with COVID‐19‐associated cryptogenic AIS, suggesting its inclusion in the diagnostic workup of these patients.

Aims To explore the management of hypertensive patients by general cardiologists a few months after the European Society of Cardiology (ESC)–European Society of Hypertension (ESH) Guidelines publication. Methods and results A survey based on a 26-point questionnaire was sent to ∼69 000 worldwide ESC members, a few months after the ESC–ESH Guidelines publication. A total of 1458 responses were collected via a web-based form. Among them, 68% were men, 48% were below 45 years old, and 60% were from Europe. Current guidelines have been read, at least partially, by 92.8%. Measurement of blood pressure (BP) is mostly done using the auscultatory method (58.8%) while unattended BP is rarely performed. Different bladder cuffs are not available for different arm circumferences for 27% of responders. Routine workup in hypertensive patients includes more often 12 leads ECG (97.7%) and echocardiography (79.6%). Only 30.9% of responders systematically assess the cardiovascular risk by the SCORE system and orthostatic hypotension is systematically researched by only 39.1%. Respondents consider that BP target of 140/90 mmHg is achievable in 60–80% of patients and 130/80 mmHg in 40–60%. Guidelines are considered too tight to be achievable by 15.6%, while 77.4% consider they are exactly right. Low patient’s compliance, awareness of hypertension (HT) risk, and, at a lower degree, physician inertia, represent the main treatment challenges in reaching BP goals to most respondents, while treatment effectiveness is not in question. The present survey demonstrates specific gaps in HT management that need attention in clinical practice.

Cardiovascular (CV) engagement in coronavirus disease 2019 (COVID‐19) is a huge determinant of prognosis during the acute phase of the disease. However, little is known about the potential chronic implications of the late phase of COVID‐19 and about the appropriate approach to these patients. Heart failure, type 1 and type 2 myocardial infarction, arrhythmias, myocarditis, pulmonary fibrosis, and thrombosis have been shown to be related to severe acute respiratory syndrome coronavirus 2 infection, and a ‘long COVID‐19’ illness has been recognized with fatigue, chest pain, and dyspnoea among the most frequent symptoms reported after discharge from hospital. This paper focuses on some open questions that cardiologists are going to face during the next months in a general cardiology outpatient clinic, in particular how to evaluate a ‘post‐COVID’ patient during follow‐up of CV complications of the acute phase and how to manage new CV symptoms that could be the consequence, at least in part, of heart/vessels and/or lung involvement of the previous virus infection. Present symptoms and signs, history of previous CV disease (both preceding COVID‐19 and occurring during viral infection), and specific laboratory and imaging measurements during the acute phase may be of interest in focusing on how to approach the clinical evaluation of a post‐COVID patient and how to integrate in our standard of care the new information on COVID‐19, possibly in a multidisciplinary view. Dealing with the increased COVID‐associated CV risk burden and becoming acquainted with potential new e‐cardiology approaches aimed at integrating the cardiology practice are relevant new challenges brought by severe acute respiratory syndrome coronavirus 2 infection and its sequelae.

Every patient before, during and after a cancer treatment, may need an imaging evaluation to manage their clinic path. Essentially will be required methods able to evaluate very accurately left ventricular function, structure, and morphology, coronary diseases, valvular heart diseases, pericardial diseases, vascular diseases, amyloidosis, myocarditis, and pulmonary hypertension. Echocardiographic methods are the most diffuse, easy to use, with low costs, and without radiation use, but are subject to difficulties in evaluation for many technic reasons. Where echocardiography is not able to give correct information, cardiac magnetic resonance (CMR) is the most promising imaging tool, also if costs and availability may preclude its diffuse use. On the other hand scintigraphy methods, due to their radiation related risk, are less utilized. The chapter analyses the main pathologic cancer related toxicities and the most useful imaging methods to be used in clinical practice.

Introduction: Nusinersen is a recent promising therapy approved for the treatment of spinal muscular atrophy (SMA), a rare disease characterized by the degeneration of alpha motor neurons (αMN) in the spinal cord (SC) leading to progressive muscle atrophy and dysfunction. Muscle and cervical SC quantitative magnetic resonance imaging (qMRI) has never been used to monitor drug treatment in SMA. The aim of this pilot study is to investigate whether qMRI can provide useful biomarkers for monitoring treatment efficacy in SMA.Methods: Three adult SMA 3a patients under treatment with nusinersen underwent longitudinal clinical and qMRI examinations every 4 months from baseline to 21-month follow-up. The qMRI protocol aimed to quantify thigh muscle fat fraction (FF) and water-T2 (w-T2) and to characterize SC volumes and microstructure. Eleven healthy controls underwent the same SC protocol (single time point). We evaluated clinical and imaging outcomes of SMA patients longitudinally and compared SC data between groups transversally.Results: Patient motor function was stable, with only Patient 2 showing moderate improvements. Average muscle FF was already high at baseline (50%) and progressed over time (57%). w-T2 was also slightly higher than previously published data at baseline and slightly decreased over time. Cross-sectional area of the whole SC, gray matter (GM), and ventral horns (VHs) of Patients 1 and 3 were reduced compared to controls and remained stable over time, while GM and VHs areas of Patient 2 slightly increased. We found altered diffusion and magnetization transfer parameters in SC structures of SMA patients compared to controls, thus suggesting changes in tissue microstructure and myelin content.Conclusion: In this pilot study, we found a progression of FF in thigh muscles of SMA 3a patients during nusinersen therapy and a concurrent slight reduction of w-T2 over time. The SC qMRI analysis confirmed previous imaging and histopathological studies suggesting degeneration of αMN of the VHs, resulting in GM atrophy and demyelination. Our longitudinal data suggest that qMRI could represent a feasible technique for capturing microstructural changes induced by SMA in vivo and a candidate methodology for monitoring the effects of treatment, once replicated on a larger cohort.

Background and purpose Manual segmentation of white matter (WM) bundles requires extensive training and is prohibitively labor-intensive for large-scale studies. Automated segmentation methods are necessary in order to eliminate operator dependency and to enable reproducible studies. Significant changes in the WM landscape throughout childhood require flexible methods to capture the variance across the span of brain development. Methods Here, we describe a novel automated segmentation tool called Cortically Constrained Shape Recognition (CCSR), which combines two complementary approaches: (1) anatomical connectivity priors based on FreeSurfer-derived regions of interest and (2) shape priors based on 3-dimensional streamline bundle atlases applied using RecoBundles. We tested the performance and repeatability of this approach by comparing volume and diffusion metrics of the main language WM tracts that were both manually and automatically segmented in a pediatric cohort acquired at the UCSF Dyslexia Center (n = 59; 25 females; average age: 11 ± 2; range: 7-14). Results The CCSR approach showed high agreement with the expert manual segmentations: across all tracts, the spatial overlap between tract volumes showed an average Dice Similarity Coefficient (DSC) of 0.76, and the fractional anisotropy (FA) on average had a Lin's Concordance Correlation Coefficient (CCC) of 0.81. The CCSR's repeatability in a subset of this cohort achieved a DSC of 0.92 on average across all tracts. Conclusion This novel automated segmentation approach is a promising tool for reproducible large-scale tractography analyses in pediatric populations and particularly for the quantitative assessment of structural connections underlying various clinical presentations in neurodevelopmental disorders.

Background The primary aim of this study was to provide additional data of neuroimaging features of coronavirus disease 2019 (COVID-19) in a large-scale population admitted in several northern Italy institutions. The secondary aim was to analyze acute cerebrovascular disease (CVD) prevalence in COVID-19. Methods A database of confirmed COVID-19 hospitalized patients who developed acute neurological symptoms and underwent any neuroimaging was retrospectively gathered from twelve institutions based in Lombardy from February 21st to July 10th. To assess the prevalence of CVD we conducted a scoping review following the PRISMA extension guidelines for scoping reviews. We searched PubMed/Medline, SCOPUS and EMBASE databases for peer-reviewed in-press or published studies from December to January 2021 reporting CVD in COVID-19 patients. Results Out of 90 COVID-19 patients who were referred to neuroimaging, 78 (87%) showed CVD, in particular 65 had acute ischemic strokes (AIS), 8 had intracerebral hemorrhages, 2 subarachnoid hemorrhages (SAH) and 3 showed clinical and imaging findings in keeping with posterior reversible encephalopathy syndrome (PRES); 6 patients (7%) showed clinical and imaging findings highly suggestive of encephalitis; 3 patients (3%) showed demyelinating diseases: 1 case of MS progression, 1 case of newly diagnosed MS and 1 case of acute disseminated encephalomyelitis (ADEM); 2 cases (2%) acuity of chronic subdural hematoma (cSDH); 1 patient (1%) with Guillain Barré syndrome. In addiction two patients with CVD developed cauda polyradiculitis and tetraparesis. In our scoping review out of 3275 studies, 24 satisfied the inclusion criteria: in a pooled total population of 136198 patients, the pooled prevalence of CVD was 0.9%. In particular 0.8% of AIS and 0.1% of ICH and 0.003% of PRES. Conclusions Our study shows a high prevalence of CVD among patients who developed acute neurological symptoms, which is in line with papers reporting data comparable to ours. The heterogeneity of clinical reports, however, constitutes a limitation when comparing our findings with those of the clinical papers. Nonetheless, CVD could be a frightening association with COVID-19, particularly in critically ill patients. Healthcare policymakers and clinicians should be prepared to a likely increase in workload and to rearrange the strategy of healthcare delivery.

Advances in treatment, common cardiovascular (CV) risk factors and the ageing of the population have led to an increasing number of cancer patients presenting with acute CV diseases. These events may be related to the cancer itself or the cancer treatment. Acute cardiac care specialists must be aware of these acute CV complications and be able to manage them. This may require an individualized and multidisciplinary approach. We summarize the most common acute CV complications of cytotoxic, targeted, and immune-based therapies. This is followed by a proposal for a multidisciplinary approach where acute cardiologists work close together with the treating oncologists, haematologists, and radiation specialists, especially in situations where immediate therapeutic decisions are needed. In this first part, we further focus on the management of acute coronary syndromes and acute pericardial diseases in patients with cancer.

Purpose We describe the reorganization carried out during the COVID-19 outbreak at one of the stroke centers in Italy and report on the clinical features and procedural variables of stroke patients in need of endovascular treatment. Methods From 1 March to 10 May 2020, we retrospectively analyzed data from stroke patients in need of urgent neurointerventional treatment. Clinical presentation, demographics, and clinical history were collected along with procedural variables (door-to-needle time, needle-to-mTiCi time). Each patient underwent a nasal swab (polymerase chain reaction test), clinical screening, and chest CT scan to assess the risk of SARS-CoV-2 infection. Technical success, procedural safety (including staff SARS-CoV-2 infection), and clinical outcome at discharge were retrieved. A comparison was made with the same patient population treated between 1 March and 10 May 2019 to highlight possible differences in the characteristics or outcomes of the patients. Results One hundred thirty-six ischemic stroke patients were admitted to our facility from 1 March to 10 May 2020. Of these, 12 patients (9%) were classified as “high risk” for SARS-CoV-2 infection. Radiological suspicion of COVID-19 was confirmed in all cases by pharyngeal swab. Five SARS-CoV-2 patients (42%) needed endovascular therapy. None of the staff members tested positive for IgG against SARS-CoV-2. Compared to the same period in 2019, an increase in the mean interval from the first symptoms to hospital arrival was observed (p

Failure to thrive (FTT) is an abnormal growth pattern determined by inadequate nutrition. It is a common problem in children, representing 5% to 10% of patients seen in an outpatient setting. Many definitions have been proposed based on anthropometric deterioration; however, they show poor concordance. No single definition is sufficiently sensitive in identifying faltering growth whilst a combination of multiple criteria seems more accurate. In light of the recent redefinition of pediatric malnutrition as a disequilibrium between requirements and intakes of energy, and macro- and micronutrients, a wider conception of FTT as an unsatisfactory nutritional status related to poor growth and health is useful. Although the most severe problems of micronutrient malnutrition are found in developing countries, people of all regions of the world can be affected by micronutrient deficiencies (MNDs), a form of undernutrition with relevant effects on growth and health. Changes in diets and lifestyle, elimination diets, food insecurity, and food intake disorders create the conditions at risk of faltering growth and MNDs. This new insight integrates the “classical” anthropometric criteria for definition and treatment, in the aim of warranting both a regular increase in size and an overall adequate development and health status.

BACKGROUND AND PURPOSE Neurological and neurodegenerative diseases can affect the spinal cord (SC) of pediatric patients. Magnetic resonance imaging (MRI) allows for in vivo quantification of SC atrophy via cross-sectional area (CSA). The study of CSA values in the general population is important to disentangle disease-related changes from intersubject variability. This study aimed at providing normative values for cervical CSA in children, extending our previous work performed with adults. METHODS Seventy-eight children (age 7-17 years) were selected from a Developmental Dyslexia study. All subjects underwent a 3T brain MRI session and any incidental findings were reported on the scans. A sagittal 1 mm3 3-dimensional T1 -weighted brain acquisition extended to the upper cervical cord was used to measure CSA at C2-C3, as well as spinal canal area and skull volume (V-scale). These three metrics were linearly fitted as a function of age to extract trends and percentage annual changes. Sex differences of CSA were assessed using least squares regression analyses, adjusting for age. We tested normalization strategies proven to be effective in reducing the intersubject variability of adults' CSA. RESULTS CSA changed as a function of age at a faster rate when compared with skull volume (CSA: 1.82% increase, V-scale: .60% reduction). Sex had a statistically significant effect on CSA. Normalization methods based on canal area and skull volume reduced the CSA intersubject variability up to 16.84%. CONCLUSIONS We present CSA normative values in a large cohort of children, reporting on sources of intersubject variability and how to reduce them applying normalization methods previously developed.

BACKGROUND AND PURPOSE: MR imaging is essential for MS diagnosis and management, yet it has limitations in assessing axonal damage and remyelination. Gadolinium-based contrast agents add value by pinpointing acute inflammation and blood-brain barrier leakage, but with drawbacks in safety and cost. Neurite orientation dispersion and density imaging (NODDI) assesses microstructural features of neurites contributing to diffusion imaging signals. This approach may resolve the components of MS pathology, overcoming conventional MR imaging limitations. MATERIALS AND METHODS: Twenty-one subjects with MS underwent serial enhanced MRIs (12.6 ± 9 months apart) including NODDI, whose key metrics are the neurite density and orientation dispersion index. Twenty-one age- and sex-matched healthy controls underwent unenhanced MR imaging with the same protocol. Fifty-eight gadolinium-enhancing and non-gadolinium-enhancing lesions were semiautomatically segmented at baseline and follow-up. Normal-appearing WM masks were generated by subtracting lesions and dirty-appearing WM from the whole WM. RESULTS: The orientation dispersion index was higher in gadolinium-enhancing compared with non-gadolinium-enhancing lesions; logistic regression indicated discrimination, with an area under the curve of 0.73. At follow-up, in the 58 previously enhancing lesions, we identified 2 subgroups based on the neurite density index change across time: Type 1 lesions showed increased neurite density values, whereas type 2 lesions showed decreased values. Type 1 lesions showed greater reduction in size with time compared with type 2 lesions. CONCLUSIONS: NODDI is a promising tool with the potential to detect acute MS inflammation. The observed heterogeneity among lesions may correspond to gradients in severity and clinical recovery after the acute phase.

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Background and purpose The quantification of spinal cord (SC) atrophy by MRI has assumed an important role in assessment of neuroinflammatory/neurodegenerative diseases and traumatic SC injury. Recent technical advances make possible the quantification of gray matter (GM) and white matter tissues in clinical settings. However, the goal of a reliable diagnostic, prognostic or predictive marker is still elusive, in part due to large intersubject variability of SC areas. Here, we investigated the sources of this variability and explored effective strategies to reduce it. Methods One hundred twenty-nine healthy subjects (mean age: 41.0 ± 15.9) underwent MRI on a Siemens 3T Skyra scanner. Two-dimensional PSIR at the C2-C3 vertebral level and a sagittal 1 mm3 3D T1-weighted brain acquisition extended to the upper cervical cord were acquired. Total cross-sectional area and GM area were measured at C2-C3, as well as measures of the vertebra, spinal canal and the skull. Correlations between the different metrics were explored using Pearson product-moment coefficients. The most promising metrics were used to normalize cord areas using multiple regression analyses. Results The most effective normalization metrics were the V-scale (from SienaX) and the product of the C2-C3 spinal canal diameters. Normalization methods based on these metrics reduced the intersubject variability of cord areas of up to 17.74%. The measured cord areas had a statistically significant sex difference, while the effect of age was moderate. Conclusions The present work explored in a large cohort of healthy subjects the source of intersubject variability of SC areas and proposes effective normalization methods for its reduction.

Advances in cancer treatments have improved clinical outcomes, leading to an increasing population of cancer survivors. However, this success is associated with high rates of short‐ and long‐term cardiovascular (CV) toxicities. The number and variety of cancer drugs and CV toxicity types make long‐term care a complex undertaking. This requires a multidisciplinary approach that includes expertise in oncology, cardiology and other related specialties, and has led to the development of the cardio‐oncology subspecialty. This paper aims to provide an overview of the main adverse events, risk assessment and risk mitigation strategies, early diagnosis, medical and complementary strategies for prevention and management, and long‐term follow‐up strategies for patients at risk of cancer therapy‐related cardiotoxicities. Research to better define strategies for early identification, follow‐up and management is highly necessary. Although the academic cardio‐oncology community may be the best vehicle to foster awareness and research in this field, additional stakeholders (industry, government agencies and patient organizations) must be involved to facilitate cross‐discipline interactions and help in the design and funding of cardio‐oncology trials. The overarching goals of cardio‐oncology are to assist clinicians in providing optimal care for patients with cancer and cancer survivors, to provide insight into future areas of research and to search for collaborations with industry, funding bodies and patient advocates. However, many unmet needs remain. This document is the product of brainstorming presentations and active discussions held at the Cardiovascular Round Table workshop organized in January 2020 by the European Society of Cardiology.

Congenital Disorders of Glycosylation (CDG) are genetic diseases caused by hypoglycosylation of glycoproteins and glycolipids. Most CDG are multisystem disorders with mild to severe involvement. We studied 554 patients (2007–2017) with a clinical phenotype compatible with a CDG. Screening was performed by serum transferrin isoelectric focusing. The diagnosis was confirmed by genetic testing (Sanger or exome sequencing). A confirmed abnormal pattern was found in nine patients. Seven patients showed a type 1 pattern: four with PMM2-CDG, two with ALG2-CDG, and one with classical galactosemia. A type 2 pattern was found in two patients: one with a CDG-IIx and one with a transferrin protein variant. Abnormal transferrin pattern were observed in a patient with a myopathy due to a COL6A2 gene variant. CDG screening in Argentina from 2007 to 2017 revealed 4 PMM2-CDG patients, 2 ALG2-CDG patients with a novel homozygous gene variant and 1 CDG-IIx.

Background Transcatheter aortic valve implantation (TAVI) continues to gain popularity in the management of patients with severe aortic stenosis (SAS). Distribution of resources to maximise appropriate use remains a priority. Design & methods To determine the current perceptions and behaviours regarding SAS patient management, an 18-point multiple-choice questionnaire was distributed to European Society of Cardiology (ESC) Council for Cardiology Practice (CCP) e-journal and/or electronic newsletter subscribers. Respondents to all questions were considered. Sub-analyses based on respondent age, practice setting and geographical location were performed. Results Of 1245 full respondents, 41.5% were aged ≥ 51 years, 22.7% were aged 41–50 years and 35.8% were aged ≤ 40 years. The majority were located in Europe (77.5%), followed by Asia/Oceania (11.6%), America (7.6%) and Africa (3.4%). In-hospital and out-of-hospital cardiologists accounted for 57.4% of and 28.5% of the sample, respectively, with the remainder being general practitioners/other. The majority of respondents (70.1%) claimed to diagnose between one and five cases of SAS per month. Free access to TAVI was reported by 41.2%, being less common for those aged ≤ 40 years (32.7%; p Conclusion The population of potential TAVI is significant worldwide, with key barriers to referral being access limitations and poor physician education. Strategies to minimise these factors are paramount.

Domestic animals under close confinement conditions frequently display abnormal behaviour, particularly if they are unable to escape from, or adapt to this situation. With the increased interest in domestic farm animal welfare from both the political and societal agendas, environmental enrichment (EE) is becoming an interesting solution, offering an alternative not only to optimize the welfare of the animals but to improve the animals' performance. In general, the development of more intensive production systems and specialized techniques has provided benefits in terms of productivity, but at the expense of the behavioural needs and welfare of kept animals. In intensive farming, welfare concerns are still often related to barren environments and crowded conditions. Producers need to balance the requirements to improve welfare conditions on the farm with practical considerations. This paper provides a review of the scientific literature, focusing on recent advances on the welfare-relevant consequences of EE on harmful social behaviours due to intensively farmed confinement in pigs, laying hens and dairy calves, including a discussion with regard to their relevance and suitability.

Objective In this study we investigated the potential of magnetic resonance (MR) micro-neurography to detect morphological and relaxometric changes in distal tibial nerves in patients affected with chronic inflammatory demyelinating polyneuropathy (CIDP), and their associations with clinical and electrophysiological features. Materials and methods 10 subjects affected with CIDP and 10 healthy subjects were examined. Multiple MR parameters, including the number of fascicles (N), fascicles diameter (FD), total fascicles area (FA), epineurium area (EA), total nerve area (NA), fascicles to nerve ratio (FNR) and quantitative T2 and proton density (PD) were investigated on high resolution MR images of the distal tibial nerve. Those parameters were correlated with clinical scores, age of onset, disease duration and electrophysiologic data. Results Median NA and FA were significantly increased in the CIDP population (median values for NA in cm2 in CIDP: 0.185; controls: 0.135; p: 0.028; for FA in CIDP 0.136; controls 0.094; p: 0.021). There was no correlation between the parameters investigated and clinical or electrophysiologic features. Conclusion MR microneurography can detect increased total nerve and fascicle area in distal tibial nerves in CIDP and may be useful for diagnosing CIDP.

Aims Anticancer therapies have extended the lives of millions of patients with malignancies, but for some this benefit is tempered by adverse cardiovascular (CV) effects. Cardiotoxicity may occur early or late after treatment initiation or termination. The extent of this cardiotoxicity is variable, depending on the type of drug used, combination with other drugs, mediastinal radiotherapy, the presence of CV risk factors, and comorbidities. A recent position paper from the European Society of Cardiology addressed the management of CV monitoring and management of patients treated for cancer. Methods and results The current document is focused on the basis of the Cardio-Oncology (C-O) Services, presenting their rationale, organization, and implementation. C-O Services address the spectrum of prevention, detection, monitoring, and treatment of cancer patients at risk of cardiotoxicity and/or with concomitant CV diseases. These services require a multidisciplinary approach, with the aims of promoting CV health and facilitating the most effective cancer therapy. Conclusion The expected growing volume of patients with cancer at risk of developing/worsening CV disease, the advent of new technological opportunities to refine diagnosis, and the necessity of early recognition of cancer therapy-related toxicity mandate an integrative multidisciplinary approach and care in a specialized environment. This document from the ESC Cardio-Oncology council proposes the grounds for creating C-O Services in Europe based on expert opinion.

The Task Force for the diagnosis and management of syncope of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) Endorsed by: European Academy of Neurology (EAN), European Federation of Autonomic Societies (EFAS), European Federation of Internal Medicine (EFIM), European Union Geriatric Medicine Society (EUGMS), European Society of Emergency Medicine (EuSEM) (text is available in electronic version doi:10.15829/1560-4071-2019-7-130-194)

2-D : two-dimensional 3-D : three-dimensional 5-FU : 5-fluorouracil ACE : angiotensin-converting enzyme ARB : angiotensin II receptor blocker ASE : American Society of Echocardiography BNP : B-type natriuretic peptide CABG : coronary artery bypass graft CAD : coronary artery

Radiation therapy (RT) causes inflammation, activation of pro-fibrotic cytokines, and endothelial and microvascular damage. Radiation increases oxidative stress through free radical production and results in recruitment of matrix metalloproteinases and pro-inflammatory mediators. These changes may lead to acute toxicity (evident during or shortly after radiotherapy) and start a chronic process leading to delayed dysfunction that is evident several years later. Acute changes largely result from direct radiation damage and the immediate inflammatory response, while long-term changes are due to stem cell loss and late and persistent tissue fibrosis. Thus, chronic radiation-induced damage is irreversible and can affect multiple cardiac structures including the coronary arteries, myocardium, pericardium, cardiac valves, and the conduction system. The incidence of acute pericarditis has decreased over time from 20 % to 2.5 % with modern radiation techniques; therapy is the same as for acute viral or idiopathic pericarditis. Ventricular dysfunction is a rare event. It is more frequent when an anthracycline or high-dose chemotherapy is administered concurrently, or shortly before RT, since radiation interacts synergistically to induce myocardial damage.Delayed radiation-induced heart disease (RIHD) is a significant problem, especially in long-term survivors of lymphoma and breast cancer. The median time from RT to appearance of clinically significant RIHD is 15 years, with the incidence increasing progressively over time. All the patients treated with mediastinal or chest radiotherapy more than 10 years ago should be object of an active program of prevention and follow-up. The follow-up should last lifelong. Many cancer patients who achieved complete remission are dismissed by the oncological follow-up after 5–10 years. Few patients have the opportunity to be included in a cancer survivor clinic for long-term follow-up of treatment-related disease. The general practitioners and the cardiologists should take care of this problem. The group at highest risk is represented by childhood cancer survivors, and this problem has been addressed in Chap. 16. Coronary Artery Disease (CAD) is the most frequent and relevant form of RIHD. The risk of death due to acute myocardial infarction (AMI) is two- to fourfold higher in patients treated for Hodgkin lymphoma compared with age-matched controls, but can be increased sevenfold or higher in some subgroups. The mechanism involved in plaque formation is thought to mirror spontaneous atherosclerosis; however, plaques in irradiated patients have been found to be more fibrous with decreased lipid content, and the lesions are consistently more proximal, smoother, concentric, tubular, and longer. Left ventricular (LV) dysfunction is a frequent complication of chest RT, and may be due to: macroscopic CAD leading to chronic ischemia; decrease in capillary density resulting in myocyte hypoxia; direct myocyte damage and necrosis, more evident in synergy with anthracycline cardiotoxicity, with progressive fibrosis replacing viable myocardial tissue; increase in type I collagen rather than type III collagen, leading to reduced myocardial distensibility. Valvular heart disease (VHD) ranges from sclerosis to severe, often calcific, valvular stenosis and/or regurgitation. It is more common after mediastinal RT in comparison to chest wall RT for breast cancer. Among breast cancer patients, it is more common after left-sided RT in comparison to right-sided RT. Chronic pericarditis may develop as a consequence of acute pericarditis seen during or shortly after RT and as a delayed complication. Most patients have a combination of restrictive and constrictive disease and pericardial stripping does not afford similar benefits in RT patients compared to those with constriction due to other causes. Arrhythmias can be seen as a consequence of RT, and may be both hyperkinetic and hypokinetic. Inappropriate sinus tachycardia, both at rest and during effort, is common after thoracic RT and is felt to be a consequence of autonomic dysfunction. Bundle branch and atrio-ventricular blocks may also be observed. Radiation-induced carotid disease produces carotid lesions that are more extensive than the traditional bifurcation stenosis and often involves atypical areas such as long segments of the carotid artery. The global risk of cerebrovascular events is increased and the common atherosclerosis risk factors and preexisting atherosclerotic lesions are exacerbating factors In patients presenting with symptoms of dyspnea, fatigue, and reduced exercise tolerance, it is important to consider other organs that may be affected by RT or chemotherapy in the differential diagnosis: acute, chronic and recall radiation pneumonitis should be ruled out; chemotherapyinduced lung disease may be observed with several agents, mostly with bleomycin; radiation fields including the neck (such as mantle field used for HL) may cause thyroid dysfunction, most frequently hypothyroidism..

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Guidelines summarize and evaluate all available evidence on a particular issue at the time of the writing process, with the aim of assisting health professionals in selecting the best management strategies for an individual patient with a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines and recommendations should help health professionals to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate.

To assess over a period of 9 months in a sample of Italian Parkinson’s disease (PD) patients reasons leading the neurologist to modify dopaminergic treatment and patients’ causes of dissatisfaction with ongoing therapy. To evaluate the influence of disease severity on therapy persistence. A disease severity balanced sample of PD patients with stable anti-parkinsonian drugs (APD) treatment was enrolled and evaluated every 3 months. Patients requiring APD treatment modifications were discontinued from the study. The probability to modify APD treatment is greater for higher motor (UPDRS scores) and non-motor symptoms (NMSS score) severity. Both from neurologist’s and patient’s perspective, motor symptoms were the main determinants underlying APD treatment modifications. Non-motor symptoms were cause of dissatisfaction with ongoing APD treatment for 52 % of the patients, while only 36 % of the neurologists considered these as valid reasons for therapy change. REASON is the first study in PD patients that prospectively examined reasons driving APD treatment changes. Results show that the disease severity significantly increases the probability of APD treatment change. Patients attribute greater relevance than neurologists to non-motor symptoms as reason requiring treatment changes. This confirms that patient and neurologist perceptions only partially overlap.

Information about patients' adherence to therapy represents a primary issue in Parkinson's disease (PD) management. To perform the linguistic validation of the Italian version of the self-rated 8-Item Morisky Medical Adherence Scale (MMAS-8) and to describe in a sample of Italian patients affected by PD the adherence to anti-Parkinson drug therapy and the association between adherence and some socio-demographic and clinical features. MMAS-8 was translated into Italian language by two independent Italian mother-tongue translators. The consensus version was then back-translated by an English mother-tongue translator. This translation process was followed by a consensus meeting between the authors of translation and investigators and then by two comprehension tests. The translated version of the MMAS-8 scale was then administered at the baseline visit of the "REASON" study (Italian Study on the Therapy Management in Parkinson's disease: Motor, Non-Motor, Adherence and Quality Of Life Factors) in a large sample of PD patients. The final version of the MMAS-8 was easily understood. Mean ± SD MMAS-8 score was 6.1 ± 1.2. There were no differences in adherence to therapy in relationship to disease severity, gender, educational level or decision to change therapy. The Italian version of MMAS-8, the key tool of the REASON study to assess the adherence to therapy, has shown to be understandable to patients with PD. Patients enrolled in the REASON study showed medium therapy adherence.

OBJECTIVES: To assess the association between clinical and socio-demographic features and anti-Parkinson drug (APD) treatment modifications in patients with PD and to describe neurologist and patient opinions regarding the need for changes in APD therapy. METHODS: Subjects with PD with stable APD treatment over ≥3 months prior to baseline were enrolled and evaluated for socio-demographic data, disability, disease severity and neurologist and patient views on the need to modify APD treatment. RESULTS: 775 Patients were included, 51% with Hoehn and Yahr (HY) stage 1-2 (early PD) and 49% with HY stage 2.5-4 (advanced PD). Neurologists modified APD treatment in 255 patients, 97 (25%) early PD and 158 (41%; p < 0.0001) advanced PD. APD modification was strongly associated with a low educational level and UPDRS part IV score. The most common reasons behind the APD therapy changes among neurologists were presence/worsening of motor or non-motor symptoms (88% and 37% of subjects respectively). Out of 216 patients, 92% and 51% were willing to undergo APD changes to therapy because of the presence/worsening of motor or non-motor symptoms. CONCLUSIONS: Neurologist decision to change APD therapy and patients reasons for dissatisfaction with it can be prevalently attributed to the presence/worsening of motor symptoms and motor fluctuations in the advanced stages. Non-motor symptoms were considered more often by patients. The patient educational level played a key role in treatment decision.

AIMS Our aim was to assess the effects on clinical outcomes of endovascular treatment vs. thrombolysis alone in patients with ischaemic stroke. METHODS AND RESULTS PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for randomised trials comparing endovascular treatment vs. intravenous thrombolysis alone in acute ischaemic stroke. Data were pooled by meta-analysis using a fixed-effects or a random-effects model, as appropriate. Eight studies enrolling 2,423 participants were included. Compared with thrombolysis alone, endovascular treatment was associated with higher rates of 90-day modified Rankin Scale (mRS) scores of 0-2 (42.4% vs. 31.8%, odds ratio [OR] 1.71, 95% confidence interval [CI]: 1.17-2.49, p=0.005, number needed to treat to benefit [NNTB]=8), and of recanalisation at 24-30 hours (76.9% vs. 39.6%, OR 4.49, 95% CI: 2.41-8.38, p

Scientific debate over chronic cerebrospinal venous insufficiency (CCSVI) has drawn attention to venous system involvement in a series of pathologic brain conditions. In the last few decades, the MRI venography (MRV) field has developed a number of valuable sequences to better investigate structural anatomy, vessel patency, and flow characteristics of venous drainage in the intra- and extracranial systems. A brief two-tier protocol is proposed to encompass the study of intra- and extracranial venous drainage with and without contrast administration, respectively. Contrast-enhanced protocol is based on time-resolved contrast-enhanced MRV of the whole region plus extracranial flow quantification through 2D Cine phase contrast (PC); non-contrast-enhanced protocol includes intracranial 3D PC, extracranial 2D time of flight (TOF), and 2D Cine PC flow quantification. Total scanning time is reasonable for clinical applications: approximately seven minutes is allocated for the contrast protocol (most of which is due to 2D Cine PC), while the noncontrast protocol accounts for around twenty minutes. We believe that a short though exhaustive MRI scan of the whole intra- and extracranial venous drainage system can be valuable for a variety of pathologic conditions, given the possible venous implication in several neurological conditions.