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Aims To develop quality indicators (QIs) for the evaluation of the prevention and management of cancer therapy-related cardiovascular toxicity. Methods and results We followed the European Society of Cardiology (ESC) methodology for QI development which comprises (i) identifying the key domains of care for the prevention and management of cancer therapy-related cardiovascular toxicity in patients on cancer treatment, (ii) performing a systematic review of the literature to develop candidate QIs, and (iii) selecting of the final set of QIs using a modified Delphi process. Work was undertaken in parallel with the writing of the 2022 ESC Guidelines on Cardio-Oncology and in collaboration with the European Haematology Association, the European Society for Therapeutic Radiology and Oncology and the International Cardio-Oncology Society. In total, 5 main and 9 secondary QIs were selected across five domains of care: (i) Structural framework, (ii) Baseline cardiovascular risk assessment, (iii) Cancer therapy related cardiovascular toxicity, (iv) Predictors of outcomes, and (v) Monitoring of cardiovascular complications during cancer therapy. Conclusion We present the ESC Cardio-Oncology QIs with their development process and provide an overview of the scientific rationale for their selection. These indicators are aimed at quantifying and improving the adherence to guideline-recommended clinical practice and improving patient outcomes.

Gonadotropin-releasing hormone isoform I (GnRH), a neuro-deca-peptide, plays a fundamental role in development and maintenance of the reproductive system in vertebrates. The anomalous release of GnRH is observed in reproductive disorder such as hypogonadotropic hypogonadism, polycystic ovary syndrome (PCOS), or following prenatal exposure to elevated androgen levels. Quantitation of GnRH plasma levels could help to diagnose and better understand these pathologies. Here, a validated nano-high-performance liquid chromatography–high-resolution mass spectrometry (HPLC-HRMS) method to quantify GnRH in ewe plasma samples is presented. Protein precipitation and solid-phase extraction (SPE) pre-treatment steps were required to purify and enrich GnRH and internal standard (lamprey-luteinizing hormone-releasing hormone-III, l-LHRH-III). For the validation process, a surrogate matrix approach was chosen following the International Council for Harmonisation (ICH) and FDA guidelines. Before the validation study, the validation model using the surrogate matrix was compared with those using a real matrix such as human plasma. All the tested parameters were analogous confirming the use of the surrogate matrix as a standard calibration medium. From the validation study, limit of detection (LOD) and limit of quantitation (LOQ) values of 0.008 and 0.024 ng/mL were obtained, respectively. Selectivity, accuracy, precision, recovery, and matrix effect were assessed with quality control samples in human plasma and all values were acceptable. Sixteen samples belonging to healthy and prenatal androgen (PNA) exposed ewes were collected and analyzed, and the GnRH levels ranged between 0.05 and 3.26 ng/mL. The nano-HPLC-HRMS developed here was successful in measuring GnRH, representing therefore a suitable technique to quantify GnRH in ewe plasma and to detect it in other matrices and species. Graphical abstract

Il ruolo dell’attività fisica nella prevenzione primaria delle neoplasie è noto; negli ultimi anni l’esercizio svolto con sistematicità ha acquisito un ruolo anche in prevenzione secondaria, riducendo il rischio di recidiva di cancro e migliorando la prognosi e la qualità di vita dei pazienti. L’esercizio fisico è altresì raccomandato per prevenire e contrastare la cardiotossicità dei trattamenti neoadiuvanti e adiuvanti, e per limitare gli effetti invalidanti di fatigue, sarcopenia e cachessia. Dalla letteratura internazionale e dalle esperienze di pratica clinica emerge sempre più l’importanza di introdurre programmi di esercizioterapia nella gestione globale del paziente oncologico, con una prescrizione sartoriale concordata a livello multidisciplinare (oncologo, cardiologo, fisiatra, fisioterapista), che tenga conto della storia naturale del tipo di cancro, del rischio di complicanze, degli effetti terapeutici e collaterali delle terapie in corso, oltre a valutare problemi di sicurezza ed eventuali controindicazioni.

La reale incidenza delle aritmie e della morte improvvisa è di difficile valutazione per la peculiare condizione dei pazienti oncologici, a causa di sintomi e segni concomitanti e confondenti. Tuttavia ogni tipo di aritmia può presentarsi in questi soggetti, sia spontaneamente che a causa di condizioni favorenti, che per effetto tossico del trattamento del cancro. È comunque essenziale, perché spesso modificabile e riducibile, valutare il rischio aritmico nei pazienti con cancro. Modesti interventi, come la correzione di una dis-ionia o evitare il concomitante trattamento con farmaci con potenziale effetto prolungante il QTc, possono evitare aritmie pericolose e letali. Ciò è di particolare importanza oggi, essendo di molto migliorata con le nuove terapie sia la qualità della vita che la sopravvivenza dei pazienti oncologici.

Congenital muscular dystrophies (CMDs) are inherited, progressive and heterogeneous muscle disorders. A group of CMDs are dystroglycanopathies, also called α-dystroglycanopathies, where there is an abnormal glycosylation of protein α-dystroglycan. Hypoglycosylation of α-DG results in different severities of congenital muscular dystrophies and they present with progressive muscle weakness and loss of motor functions. This article first focuses on the CMDs, their classification according to the observed symptoms or the protein involved in the resulting phenotype. We then focus on dystroglycanopathies, the importance of its correct O-glycosylation of the α-dystroglycan given its important structural function, considering the enzymes involved in said glycosylation and the phenotypes that can result, to finally address current therapeutics for these diseases with the aim of increasing current knowledge.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com, Frailty is a health condition leading to many adverse clinical outcomes. The relationship between frailty and advanced age, multimorbidity and disability has a significant impact on healthcare systems. Frailty increases cardiovascular (CV) morbidity and mortality both in patients with or without known CV disease. Though the recognition of this additional risk factor has become increasingly clinically relevant in CV diseases, uncertainty remains about operative definitions, screening, assessment, and management of frailty. Since the burdens of frailty components and domains may vary in the various CV diseases and clinical settings, the relevance of specific frailty-related aspects may be different. Understanding these issues may allow general cardiologists a clearer focus on frailty in CV diseases and thereby make more tailored clinical decisions and therapeutic choices in outpatients. Guidance on identification and management of frailty are sparse and an international consensus document on frailty in general cardiology is lacking. Moreover, new options linked with eHealth are going to better define and manage frailty. This consensus document on definition, assessment, clinical implications, and management of frailty provides an input to integrate strategies pre- and post-acute CV events with a comprehensive view including out of hospital, office-based diagnostic and therapeutic choices, and based on a multidisciplinary team approach (general cardiologists, nurses, and general practitioners).

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Congenital disorders of glycosylation (CDG) are a heterogeneous group of genetic defects in glycoprotein and glycolipid glycan synthesis and attachment. A CDG subgroup are defects in the conserved oligomeric Golgi complex encoded by eight genes, COG1-COG8. Pathogenic variants in all genes except the COG3 gene have been reported. COG1-CDG has been reported in five patients. We report a male with neonatal seizures, dysmorphism, hepatitis and a type 2 serum transferrin isoelectrofocusing. Exome sequencing identified a homozygous COG1 variant (NM_018714.3: c.2665dup: p.[Arg889Profs*12]), which has been reported previously in one patient. We review the reported patients.

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.

Book of Abstracts for the event: "I Giovani e la Spettrometria di Massa" organized by Italian Mass Spectrometry Society in Torino, June 15, 2022

Digital health technology is receiving increasing attention in cardiology. The rise of accessibility of digital health tools including wearable technologies and smart phone applications used in medical practice has created a new era in healthcare. The coronavirus pandemic has provided a new impetus for changes in delivering medical assistance across the world. This Consensus document discusses the potential implementation of digital health technology in older adults, suggesting a practical approach to general cardiologists working in an ambulatory outpatient clinic, highlighting the potential benefit and challenges of digital health in older patients with, or at risk of, cardiovascular disease. Advancing age may lead to a progressive loss of independence, to frailty, and to increasing degrees of disability. In geriatric cardiology, digital health technology may serve as an additional tool both in cardiovascular prevention and treatment that may help by (i) supporting self-caring patients with cardiovascular disease to maintain their independence and improve the management of their cardiovascular disease and (ii) improving the prevention, detection, and management of frailty and supporting collaboration with caregivers. Digital health technology has the potential to be useful for every field of cardiology, but notably in an office-based setting with frequent contact with ambulatory older adults who may be pre-frail or frail but who are still able to live at home. Cardiologists and other healthcare professionals should increase their digital health skills and learn how best to apply and integrate new technologies into daily practice and how to engage older people and their caregivers in a tailored programme of care.

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.

Asparagine-linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X-linked uridine diphosphate (UDP)-N-acetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N-linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13-CDG. Twenty-four previously reported ALG13-CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13-CDG did not show the anticipated glycosylation defects, typically detected by altered transferrin glycosylation. Structural homology modeling of two recurrent de novo variants, p.A81T and p.N107S, suggests both are likely to impact the function of ALG13. Using a corresponding ALG13-deficient yeast strain, we show that expressing yeast ALG13 with either of the highly conserved hotspot variants rescues the observed growth defect, but not its glycosylation abnormality. We present molecular and clinical data on 29 previously unreported individuals with de novo variants in ALG13. This more than doubles the number of known cases. A key finding is that a vast majority of the individuals presents with West syndrome, a feature shared with other CDG types. Among these, the initial epileptic spasms best responded to adrenocorticotropic hormone or prednisolone, while clobazam and felbamate showed promise for continued epilepsy treatment. A ketogenic diet seems to play an important role in the treatment of these individuals. Fil: Ng, Bobby G.. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos Fil: Eklund, Erik A.. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos. Lund University; Suecia Fil: Shiryaev, Sergey A.. Sanford Burnham Prebys Medical Discovery Institute; Estados Unidos Fil: Dong, Yin Y.. University of Oxford; Reino Unido Fil: Abbott, Mary Alice. University of Massachusetts Medical School; Estados Unidos Fil: Asteggiano, Carla Gabriela. Universidad Católica de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina Fil: Bamshad, Michael J.. University of Washington; Estados Unidos Fil: Barr, Eileen. University of Emory; Estados Unidos Fil: Bernstein, Jonathan A.. University of Stanford; Estados Unidos Fil: Chelakkadan, Shabeed. Monash Children's Hospital; Australia Fil: Christodoulou, John. Sydney Medical School; Australia. University of Melbourne; Australia Fil: Chung, Wendy K.. Columbia University; Estados Unidos Fil: Ciliberto, Michael A.. University of Iowa; Estados Unidos Fil: Cousin, Janice. National Human Genome Research Institute ; Estados Unidos Fil: Gardiner, Fiona. University of Melbourne; Australia Fil: Ghosh, Suman. University of Florida; Estados Unidos Fil: Graf, William D.. University of Connecticut; Estados Unidos Fil: Grunewald, Stephanie. University College London; Estados Unidos Fil: Hammond, Katherine. University of Alabama at Birmingahm; Estados Unidos Fil: Hauser, Natalie S.. Inova, Fairfax Hospital Falls Church; Estados Unidos Fil: Hoganson, George E.. University Of Illinois At Chicago; Estados Unidos Fil: Houck, Kimberly M.. Baylor College of Medicine; Estados Unidos Fil: Kohler, Jennefer N.. University of Stanford; Estados Unidos Fil: Morava, Eva. Mayo Clinic; Estados Unidos Fil: Larson, Austin A.. University Of Colorado Anschutz Medical Campus.; Estados Unidos Fil: Liu, Pengfei. Baylor Genetics; Estados Unidos. Baylor College Of Medicine; Estados Unidos Fil: Madathil, Sujana. University of Iowa; Estados Unidos Fil: McCormack, Colleen. University of Stanford; Estados Unidos Fil: Meeks, Naomi J.L.. University Of Colorado Anschutz Medical Campus.; Estados Unidos Fil: Papazoglu, Gabriela Magali. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina

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.

ObjectiveA major challenge in multiple sclerosis (MS) research is the understanding of silent progression and Progressive MS. Using a novel method to accurately capture upper cervical cord area from legacy brain MRI scans we aimed to study the role of spinal cord and brain atrophy for silent progression and conversion to secondary progressive disease (SPMS).MethodsFrom a single-center observational study, all RRMS (n=360) and SPMS (n=47) patients and 80 matched controls were evaluated. RRMS patient subsets who converted to SPMS (n=54) or silently progressed (n=159), respectively, during the 12-year observation period were compared to clinically matched RRMS patients remaining RRMS (n=54) or stable (n=147), respectively. From brain MRI, we assessed the value of brain and spinal cord measures to predict silent progression and SPMS conversion.ResultsPatients who developed SPMS showed faster cord atrophy rates (-2.19%/yr) at least 4 years before conversion compared to their RRMS matches (-0.88%/yr, p

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

The resin of Boswellia plant species has been used since ancient times for its several bio-active curative effects. In modern times, extracts of this resin are still widely commercialized on the food supplements and nutraceuticals market. Nowadays the legislation on botanical extracts and the increasing demand for their safety and traceability are setting new standards for their chemical characterization. In this work we present an easy, feasible and rugged HPLC-UV-based approach for the quantitation of boswellic acids in food-supplement-grade resin extracts of Boswellia plant species. This method can be used for quality control purposes as well as for studying their differences in regional origin, years of harvesting and species-related differences. The method employs a C18 (3 × 150 mm, 3 µm) analytical HPLC column, and the separation is carried out through a gradient of acetonitrile/water with 0.1% formic acid. The method was validated following the ICH guidelines and used to quantitate different samples of commercial resin of Boswelliacarteri and serrata together with other samples from unknown species. The six known boswellic acids were identified and quantified in all the analyzed samples. The results were used to build a multivariate model to graphically appreciate their difference through their clustering. The model was then augmented by adding further quantitation data for boswellic acids belonging to different species of Boswellia obtained by another scientific publications to increase the number of studied samples.

A major challenge in multiple sclerosis (MS) research is the understanding of silent progression and Progressive MS. Using a novel method to accurately capture upper cervical cord area from legacy brain MRI scans we aimed to study the role of spinal cord and brain atrophy for silent progression and conversion to secondary progressive disease (SPMS).From a single-center observational study, all RRMS (n = 360) and SPMS (n = 47) patients and 80 matched controls were evaluated. RRMS patient subsets who converted to SPMS (n = 54) or silently progressed (n = 159), respectively, during the 12-year observation period were compared to clinically matched RRMS patients remaining RRMS (n = 54) or stable (n = 147), respectively. From brain MRI, we assessed the value of brain and spinal cord measures to predict silent progression and SPMS conversion.Patients who developed SPMS showed faster cord atrophy rates (-2.19%/yr) at least 4 years before conversion compared to their RRMS matches (-0.88%/yr, p 0.001). Spinal cord atrophy rates decelerated after conversion (-1.63%/yr, p = 0.010) towards those of SPMS patients from study entry (-1.04%). Each 1% faster spinal cord atrophy rate was associated with 69% (p 0.0001) and 53% (p 0.0001) shorter time to silent progression and SPMS conversion, respectively.Silent progression and conversion to secondary progressive disease are predominantly related to cervical cord atrophy. This atrophy is often present from the earliest disease stages and predicts the speed of silent progression and conversion to Progressive MS. Diagnosis of SPMS is rather a late recognition of this neurodegenerative process than a distinct disease phase. ANN NEUROL 2022;91:268-281.

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.

Il Cardiologo Generale (CG) è coinvolto nella gestione del paziente oncologico con possibili complicanze cardiovascolari (CV) sia per motivi epidemiologici, che per la correzione dei fattori di rischio comuni alle malattie CV e al cancro, che per l’individuazione e la cura di effetti tossici della terapia oncologica, soprattutto nel Follow-Up (F-U) a lungo termine. Per un’ottimale gestione del paziente Cardio-Oncologico (C-O) è necessaria una profonda azione di insegnamento ed educazione all’argomento ed una pianificazione rigorosa dell’organizzazione dei servizi di C-O che prevedano anche l’inclusione del CG.

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 of 25 (44%) EBV-seronegative but only 9 of 164 (5.5%, p&nbsp

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.

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.

Human ALG2 encodes an α 1,3mannosyltransferase that catalyzes the first steps in the synthesis of N-glycans in the endoplasmic reticulum. Variants in ALG2cause a congenital disorder of glycosylation (CDG) known as ALG2-CDG. Up to date, nine ALG2-CDG patients have been reported worldwide. ALG2-CDG is a rare autosomal recessive inherited disorder characterized by neurological involvement, convulsive syndrome of unknown origin, axial hypotonia, and mental and motor regression. In this study, we used MALDI-TOF MS to define both total serum protein and transferrin (Tf) N-glycan phenotypes in three ALG2-CDG patients carrying a c.752G > T, p.Arg251Leu ALG2 missense variant in homozygous state, as determined by exome sequencing. Comparing it to control samples, we have observed Tf under-occupancy of glycosylation site(s) typical of a defective N-glycan assembly and the occurrence of oligomannose and hybrid type N-glycans. Moreover, we have observed a slight oligomannose accumulation in total serum glyco-profiles. The increased heterogeneity of serum N-glycome in the studied patients suggests a marginal disarrangement of the glycan processing in ALG2-CDG. Previous studies reported on slightly increased concentrations of abnormal serum N-glycans in CDG-I due to defects in the mannosylation steps of dolichol-linked oligosaccharide biosynthesis. This preliminary work aims at considering serum N-glycan accumulation of high mannosylated glycoforms, such as oligomannose and hybrid type N-glycans, as potential diagnostic signals for ALG2-CDG patients., CONICET 2017–2021 (RD: 2191), MinCyT FONCyT PICT2010–2824/PID Clinic 2018; Universidad Católica de Córdoba 2015–2019, and the National Health Department of Argentina

Background and purposeMR 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 methodsTwenty-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.ResultsThe 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.ConclusionsNODDI 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.

Asparagine-linked glycosylation 13 homolog (ALG13) encodes a nonredundant, highly conserved, X-linked uridine diphosphate (UDP)-N-acetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N-linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13-CDG. Twenty-four previously reported ALG13-CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13-CDG did not show the anticipated glycosylation defects, typically detected by altered transferrin glycosylation. Structural homology modeling of two recurrent de novo variants, p.A81T and p.N107S, suggests both are likely to impact the function of ALG13. Using a corresponding ALG13-deficient yeast strain, we show that expressing yeast ALG13 with either of the highly conserved hotspot variants rescues the observed growth defect, but not its glycosylation abnormality. We present molecular and clinical data on 29 previously unreported individuals with de novo variants in ALG13. This more than doubles the number of known cases. A key finding is that a vast majority of the individuals presents with West syndrome, a feature shared with other CDG types. Among these, the initial epileptic spasms best responded to adrenocorticotropic hormone or prednisolone, while clobazam and felbamate showed promise for continued epilepsy treatment. A ketogenic diet seems to play an important role in the treatment of these individuals.

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

Background and purposeNeurological 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.MethodsSeventy-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.ResultsCSA 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%.ConclusionsWe 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.

Human ALG2 encodes an α 1,3mannosyltransferase that catalyzes the first steps in the synthesis of N-glycans in the endoplasmic reticulum. Variants in ALG2cause a congenital disorder of glycosylation (CDG) known as ALG2-CDG. Up to date, nine ALG2-CDG patients have been reported worldwide. ALG2-CDG is a rare autosomal recessive inherited disorder characterized by neurological involvement, convulsive syndrome of unknown origin, axial hypotonia, and mental and motor regression. In this study, we used MALDI-TOF MS to define both total serum protein and transferrin (Tf) N-glycan phenotypes in three ALG2-CDG patients carrying a c.752G T, p.Arg251Leu ALG2 missense variant in homozygous state, as determined by exome sequencing. Comparing it to control samples, we have observed Tf under-occupancy of glycosylation site(s) typical of a defective N-glycan assembly and the occurrence of oligomannose and hybrid type N-glycans. Moreover, we have observed a slight oligomannose accumulation in total serum glyco-profiles. The increased heterogeneity of serum N-glycome in the studied patients suggests a marginal disarrangement of the glycan processing in ALG2-CDG. Previous studies reported on slightly increased concentrations of abnormal serum N-glycans in CDG-I due to defects in the mannosylation steps of dolichol-linked oligosaccharide biosynthesis. This preliminary work aims at considering serum N-glycan accumulation of high mannosylated glycoforms, such as oligomannose and hybrid type N-glycans, as potential diagnostic signals for ALG2-CDG patients.

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.

Background and purposeBrain 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.MethodsPatients 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).ResultsThe 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.ConclusionsMRI 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.

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.

There is a high demand for a veterinary education in animal welfare (AW) with different approaches from the academic, society and trade points of view. Latin American (LA) countries members of the World Organization for Animal Health (OIE) are under the urge and should be obligated to teach AW. The aims of this article are to analyze the current drives of change on the importance of teaching animal welfare in LA, the competences recommended from international education organizations for the region, and to provide the contents on the curriculum in AW that a future veterinarian should achieve in the LA scenario, in other words to examine why teaching AW, what should be taught and how. Despite significant advances in introducing AW into veterinary training programs, much remains to be done regarding the future of this field in teaching veterinary science in Spain and LA countries, and in including this science as an independent course in programs at distinct levels to integrate the scientific, ethical and legal aspects of AW. This paper presents a proposal that was constructed with a view towards integrating diverse curricular approaches based on criteria, contents and concepts provided by the researchers and professors who collaborated in the book entitled: Bienestar Animal: Una Visión Global en Iberoamerica [Animal Welfare: A Global Vision in Ibero-America]. To ensure veterinary students will be better equipped to graduate with OIE day 1 competencies in AW, teaching approaches are needed that support project-based learning and gamification, critical thinking, reflection and collaborative learning. Keywords: Animal welfare, Study plans, Study programs, Teaching, Veterinary medicine

The benefits associated with the use of protective netting for apple orchards have been assessed in several growing regions, but no studies exist for Washington State, USA. This region experiences semi-arid conditions characterized by long days, high light intensity and high temperatures which increases the risk of plant stress and fruit sunburn damage. The aim of this study was to assess the effect of anti-hail nets on orchard microclimate, soil moisture and fruit sunburn. Seven-year-old ‘Granny Smith’/‘M9-T337’ apple trees were covered in 2014 with 20% white shade net sheltering a rectangular area. Uncovered trees served as control. Shade net reduced the maximum daily photosynthetically active radiation (PAR) by 32%, with a maximum PAR value on a sunny day of 1649 and 1222 μmol m-2 s-1 in the control and netted areas, respectively. Canopy air temperature was slightly lower during the day and higher at night under the net compared to the control. Shade nets reduced soil moisture depletion at 0-30 cm depth, resulting 20% higher than the control. No significant differences were observed deeper in the soil profile. Netting significantly decreased fruit sunburn, with 92% of harvested fruit having no sunburn damage compared to control in which 51% had no sunburn damage in 2014. Although preliminary, these results show that shade netting has the potential to reduce sunburn damage in ‘Granny Simith’ apples and water requirements in semi-arid environments and might represent an important tool for increasing yields of high quality fruit.

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.