European Task Force Research Articles

Diagnosis of arrhythmogenic cardiomyopathy: 20 years of progress and innovation

Arrhythmogenic cardiomyopathy (CMA) is a cardiac disease characterized by non-ischemic ventricular scarring and electrical instability. The diagnosis of CMA still remains challenging today and requires the use of a set of criteria, since no single diagnostic test represents the gold standard. The first diagnostic criteria were defined and disseminated in 1994 and then revised in 2010, focusing mainly on right ventricular involvement. In 2019, an international panel of experts identified the limitations of the previous diagnostic criteria. The 2020 Padua criteria included a specific pathway for the diagnosis of left ventricular variants and emphasized the need for the use of cardiac magnetic resonance imaging in the characterization of myocardial scarring. These criteria were further refined and published in 2023 as European Task Force (TF) criteria, thus gaining international recognition.Exploring the history of CMA and its diagnosis, in this review we analyze the changes and progress in the 20 years that have occurred from the first version of the criteria in 1994 to the latest in European TF of 2023, highlighting the evolution of our knowledge of the pathobiology and morpho-functional characteristics of the disease. One of the most relevant updates is undoubtedly the introduction of the concept of "scarring/arrhythmogenic cardiomyopathy", a definition that enhances the main features of the pathology and emphasizes the multiplicity of phenotypes and clinical presentations independent of etiology.

The 2023 European Task Force Criteria for Diagnosis of Arrhythmogenic Cardiomyopathy: Historical Background and Review of Main Changes.

Arrhythmogenic cardiomyopathy (ACM) is a cardiac disease featured by non-ischemic myocardial scarring linked to ventricular electrical instability. As there is no single gold-standard test, diagnosing ACM remains challenging and a combination of specific criteria is needed. The diagnostic criteria were first defined and widespread in 1994 and then revised in 2010, approaching and focusing primarily on right ventricular involvement without considering any kind of left ventricular variant or phenotype. Years later, in 2020, with the purpose of overcoming previous limitations, the Padua Criteria were introduced by an international expert report. The main novel elements were the introduction of specific criteria for left ventricular variants as well as the use of cardiac magnetic resonance for tissue characterization and scar detection. The last modifications and refinement of these criteria were published at the end of 2023 as the European Task Force criteria, by a "head-quarter" of ACM international experts, proving the emerging relevance of this condition besides its difficult diagnosis. In this review, emphasizing the progress in understanding the aetiology of the cardiomyopathy, an analysis of the new criteria is presented. The introduction of the term "scarring/arrhythmogenic cardiomyopathy" sets an important milestone in this field, underlying how non-ischemic myocardial scarring-typical of ACM-and arrhythmic susceptibility could be the main pillars of numerous different phenotypic variants regardless of etiology.

Towards the new primary care reform in Greece: a focus on patients' expectations, views and perceptions from rural healthcare centres.

Patient perception of quality of care is an essential component in evaluating healthcare delivery. This article reports data from primary health care (PHC) centers before Greece's most recent PHC reform. The study was undertaken to offer some baseline information about patient experience, support the decision-making processes taking place, and provide valuable input for future policy-making comparisons in Greece. The research was conducted across the 16 PHC centers of Epirus, a region of north-western Greece, from June to September 2017, with 532 patients rating the importance of different aspects of three main healthcare domains (clinical behavior, support and services, and organization of care) of PHC provision. The Greek version of the European Task Force on Patient Evaluations of General Practice (EUROPEP) questionnaire was implemented for research purposes. Univariate comparisons were performed for patients with and without chronic disease, using Pearson's χ2 test for categorical data. Study findings support that the organization of care domain is of highest importance and priority, with clinical behavior and support and services following closely. Among recruited patients, on average, only 2.1% of patients with a chronic disease were satisfied (rated 4 or 5 on the Likert scale) with the organization of care aspects under consideration, compared to 18.4% of patients without a chronic disease. Furthermore, only 4% of patients with a chronic disease were satisfied with the aspects examined in the clinical behavior domain, compared to 27% of patients without a chronic disease. Finally, 18% of sampled patients with a chronic disease reported being satisfied with the quality of support and services provided, compared to 38% of patients without a chronic disease. It is necessary to back up available past information to afterwards estimate reform imprinting on expectations and perceptions. The items and aspects of EUROPEP, in line with the new tasks of the personal doctor within the PHC system that patients perceive as most essential, can be used to prioritize quality improvement activities to strengthen PHC delivery in Greece. Communication skills, practices, and behavioral change skills seem to need more attention for an efficient PHC model.

European Respiratory Society guidelines for the Diagnosis and Management of Pulmonary Alveolar Proteinosis.

Pulmonary alveolar proteinosis (PAP) is a rare syndrome caused by several distinct diseases leading to progressive dyspnoea, hypoxemia, risk of respiratory failure and early death due to accumulation of proteinaceous material in the lungs. Diagnostic strategies may include computed tomography (CT) of the lungs, bronchoalveolar lavage, evaluation of antibodies against granulocyte macrophage colony stimulating factor (GM-CSF), genetic testing, and, eventually, lung biopsy. The management options are focused at removing the proteinaceous material by whole lung lavage (WLL), augmentation therapy with GM-CSF, rituximab, plasmapheresis, and lung transplantation. The presented diagnostic and management guideline aim to provide guidance to physicians managing patients with PAP. A European Respiratory Society Task Force committee composed of clinicians, methodologists, and patients with experience in PAP developed recommendations in accordance with the ERS Handbook for Clinical Practice Guidelines and the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. This included a systematic review of the literature and application of the GRADE approach to assess the certainty of the evidence and strength of recommendations. The committee formulated five PICO (Patients, Intervention, Comparison, Outcomes) questions, and two narrative questions to develop specific evidence-based recommendations. The Task Force committee developed recommendations for five PICOs. These included management of PAP with WLL, GM-CSF augmentation therapy, rituximab, plasmapheresis, and lung transplantation. Also, the committee made recommendations regarding the use of GM-CSF antibody testing, diagnostic bronchoalveolar lavage (BAL) and biopsy based on narrative questions.In addition to the recommendations, the committee provided information on the hierarchy of diagnostic interventions and therapy. The diagnosis of PAP is based on CT and BAL cytology or lung histology, whereas diagnosis of specific PAP-causing diseases requires GM-CSF antibody testing or genetic analysis. There are several therapies including WLL and augmentation therapy with GM-CSF available to treat PAP, but supporting evidence is still limited.

Role of Koebner phenomenon in predicting the clinical profile and course of vitiligo

Background: Koebner phenomenon (KP) is a clinical indicator of disease activity in vitiligo. Few studies have suggested that it may also be used to predict the clinical profile, prognosis, and response to therapy. Aims: To compare the clinical characteristics of vitiligo patients with different types of KP in an Indian population. Methods: A prospective longitudinal observational study was conducted from January to November 2016. Classification of KP was done according to the Vitiligo European Task Force guidelines into KP1-by history and KP2-by clinical examination (2A: lesions on friction areas and 2B: trauma-induced lesions). Results: Of the total 160 patients, KP was observed in 102 (63.8%) cases. Type 1 KP was seen in 43 (26.9%), type 2A in 87 (54.4%), and type 2B in 34 (21.3%) cases. Patients with KP1 and KP2B had an earlier age of presentation and disease onset, while those with KP2A had a higher age of presentation and disease onset. Incidence of other autoimmune disorders, higher BSA involvement and requirement of betamethasone oral mini pulse therapy were significantly higher in cases with KP1 and KP2A, while significantly elevated anti-thyroid peroxidase levels were seen in cases with KP2A. Also, lesser treatment response was noted among cases with KP1 and KP2A. Conclusion: KP is associated with increased disease activity and more extensive involvement of vitiligo. Type 2A KP was associated with a higher incidence of other autoimmune disorders, more extensive disease, and the use of systemic steroids for treatment, which were not seen in KP2B. Thus, these groups might define two different subsets of patients.

Circulating Podocalyxin, Tumstatin/Col-IVα3 and Chitinase 1: New Culprits in Vitiligo Occurrence.

The roles of anti-adhesive podocalyxin (PODXL), anti-angiogenetic tumstatin/ Col-IVα3 and neuro-inflammation and innate immunity modulator Chitinase 1 (CHIT-1) in the etiology of vitiligo have not been studied yet. This study was planned to detect changes in serum PODXL, tumstatin/Col-IVα3 and CHIT1 levels in vitiligo patients. This case-controlled study was performed on a total of 50 patients, 25 with vitiligo and 25 healthy controls. Participants in the vitiligo and control groups were matched in pairs for age and sex. At least 8-10 hours of overnight fasting, venous blood samples were taken from the participants in both groups and serum levels of podocalyxin, tumstatin/Col-IVα3 and CHIT 1 levels were measured by sandwich enzyme immunoassay. In the classification made according to the vitiligo European Task Force evaluation criteria, 18 of 25 vitiligo patients were in the slowly progressive phase and 7 patients were in the active progressive phase. Serum podocalyxin levels increased significantly in the vitiligo group compared to the controls (7.03±2.09 ng/ml vs. 4.99±1.20 ng/ml, p<0.02). However, serum tumstatin levels in vitiligo patients showed a significantly lower course compared to controls (4.88±1.76 ng/ml vs. 6.05±2.19 ng/nl, p<0.03). Serum CHIT-1 levels of vitiligo patients (42.4±7.22 ng/ml) were found to be significantly higher than the serum levels of the control group (34.5±5.33 ng/ml) (p<0.01). High podocalyxin and CHIT1versus low tumstatin levels are new biomarkers that support the role of anti-adhesive, anti-angiogenic and neuroinflammatory pathways in the formation of vitiligo.

Antithrombotic therapy in patients with acute coronary syndrome: similarities and differences between a European expert consensus document and the 2023 European Society of Cardiology guidelines.

Antithrombotic therapy represents the cornerstone of the pharmacological treatment in patients with acute coronary syndrome (ACS). The optimal combination and duration of antithrombotic therapy is still matter of debate requiring a critical assessment of patient comorbidities, clinical presentation, revascularization modality, and/or optimization of medical treatment. The 2023 European Society of Cardiology (ESC) guidelines for the management of patients with ACS encompassing both patients with and without ST segment elevation ACS have been recently published. Shortly before, a European expert consensus task force produced guidance for clinicians on the management of antithrombotic therapy in patients with ACS as well as chronic coronary syndrome. The scope of this manuscript is to provide a critical appraisal of differences and similarities between the European consensus paper and the latest ESC recommendations on oral antithrombotic regimens in ACS patients.

Immunosuppressive and immunomodulating therapy for atopic dermatitis in pregnancy: an appraisal of the literature.

Atopic dermatitis (AD) is the most common dermatological diagnosis during pregnancy. Treatment of AD during pregnancy can be challenging, due to the unpredictable course and the fact that the therapy needs to be safe for both the mother and the fetus. Here we present an up-to-date appraisal of the literature on the treatment options available for AD in patients planning pregnancy, during pregnancy, and during breastfeeding. All patients with AD are recommended to supplement any medical treatment with daily applications of emollients. The first step in the medical treatment for AD during pregnancy are topical corticosteroids, and/or topical tacrolimus. If required, UV-light therapy can also be considered. Treatment with systemic therapy during pregnancy should always rely on a careful risk-benefit assessment and be based on shared-decision making between the treating physician and patient. The first-line systemic treatment option is cyclosporine A, whereas azathioprine may be considered in patients already receiving this treatment prior to pregnancy. Systemic glucocorticoids may also be used. Treatment with systemic JAK inhibitors is not recommended, whereas treatment with mycophenolate mofetil and methotrexate is contraindicated. Targeted therapy with dupilumab is not generally recommended, due to lack of experience in human pregnancies, yet some case-reports on their use are emerging. These recommendations are based on the authors appraisal of existing literature and the current recommendation from the European Task Force on Atopic Dermatitis. It is always the responsibility of the treating physician to stay updated on the newest guidelines and literature when treating patients with AD during pregnancy.

The prioritization of biomarkers in the diagnostic workup of motor tauopathy

AbstractMotor tauopathies represent a spectrum of degenerative, poorly levodopa‐responsive parkinsonisms unified by the pathological accumulation of hyperphosphorylated tau protein fragments in the brain. The principal entities, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), are rare conditions (&lt;10 per 100,000) and present with non‐amnestic cognitive impairment ‐ mostly involving frontal‐subcortical networks – in around 40% of patients at baseline. Additionally, the phenotypic PSP spectrum expresses with oculomotor dysfunction, falls and bulbar symptoms at varying degrees. On the other hand, CBD tauopathy is the most frequent aetiology underlying the corticobasal syndrome (CBS) that is a multifaceted disorder characterized by a markedly asymmetric Parkinsonism with apraxia and neocortical deficits. Paralleling the clinical symptoms, the distribution of functional and metabolic impairment specifically involves different brain regions in PSP and CBD. Hence, metabolism assessment by FDG‐positron emission tomography (PET) allows for accurate distinction of motor tauopathies from other parkinsonisms or one with another (AUC 0.80 and 0.92‐0.97, respectively). In this context, the European Intersociety Consensus Diagnostic Task Force recommends the use of FDG‐PET as the first‐level diagnostic biomarker to achieve early and accurate differential diagnosis of motor tauopathies. Afterwards, the assessment of CSF biomarkers of Alzheimer’s disease (AD) is advised to identify that minority of cases of CBS underpinned by an AD aetiology (10‐20%). With this sequence of biomarkers, the diagnostic workflow aims to an early identification of motor tauopathies and advocates in‐depth etiological investigation of CBS where access to AD‐specific drugs, when available, should be considered in a non‐negligible proportion of patients.

The prioritization of biomarkers in the diagnostic workup of Lewy body disease

AbstractThe term Lewy body disease (LBD) encompasses a spectrum of neurodegenerative conditions, particularly Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB), associated with abnormal deposits of alpha‐synuclein in the brain and representing up to 20% of all neurocognitive disorders in memory clinics. Mild cognitive impairment or mild dementia precede or concur with Parkinsonism in the early stages of DLB and in a third of patients with PD at diagnosis. However, when Parkinsonism is slightly detectable, the differential diagnosis from other dementing conditions, such as Alzheimer’s disease (AD), may be challenging. For this reason, neuroimaging and electrophysiological biomarkers, divided into indicative or supportive based on their diagnostic performance over or below 80%, assist the clinical reasoning to increase the likelihood that MCI/early dementia is associated with LB. The European Intersociety Consensus Diagnostic Task Force recommends prioritizing the Dopamine transporter (DaT)‐SPECT imaging to investigate nigro‐striatal degeneration as the first biomarker (sensitivity 76%, specificity 88%), and suggests subsequently [123I]‐MIBG cardiac scintigraphy to evaluate the postganglionic sympathetic denervation in those cases (about a quarter) where DaT‐SPECT is negative but DLB is still clinically possible (AD pathology is estimated to be underlying in about 86% of these cases). In the absence of well‐validated techniques to establish the presence of brain alpha‐synuclein aggregates in vivo, the proposed sequence of biomarkers will provide the most accurate and cost‐effective biomarker‐based diagnosis of LBD.

A retrospective analysis of infantile haemangioma referrals: a comparison with the IH European Task Force 'Infantile Haemangioma Referral Score'.

Infantile haemangiomas (IH) are common vascular tumours of infancy that can have significant complications. The IH European Task Force developed the IH Referral Score (IHReS) to help non-specialists quickly identify IH that need to be referred to optimise outcomes in high-risk lesions. The aim of this study was to assess the quality of IH referrals to a national care centre and compare the IH referred to the IHReS tool. This was a retrospective cross-sectional study that collected data from a random sample of 56 IH patients over a 13-month period. Less than 10% included a photograph (8.93%) and a minority of referrals included if there were complications including ulceration (1.79%) or function threatening (8.93%). Three-quarters of patients satisfied the IHReS criteria. The IHReS screening tool is a convenient and efficient resource for non-experts to identify children who require referral to a specialist centre.

64 The Biomarker-Based Etiological Diagnosis of Neurocognitive Disorders: the European Inter-Societal Delphi Consensus

Objective:In the field of neurocognitive disorders, the perspective offered by new disease-modifying therapy increases the importance of etiological diagnosis. The prescription of cerebrospinal fluid analysis (CSF) and imaging biomarkers is a common practice in the clinic but is often driven more by personal expertise and local availability of diagnostic tools than by evidence of efficacy and cost-effectiveness analysis. This leads to a widely heterogeneous dementia care across Europe. Therefore, a European initiative is currently being conducted to establish a consensus for biomarker-based diagnosis of patients with mild cognitive impairment (MCI) and mild dementia.Participants and Methods:Since November 2020, a European multidisciplinary task force of 22 experts from 11 scientific societies have been defining a diagnostic workflow for the efficient use of biomarkers. The Delphi consensus procedure was used to bridge the gaps of incomplete scientific evidence on biomarker prioritization. The project has been in two phases. During Phase 1, we conducted a literature review on the accuracy of imaging, CSF, neurophysiological and blood biomarkers in predicting the clinical progression or in defining the underpinning aetiology of main neurocognitive disorders. Evidence was provided to support the panelists’ decisions. In phase 2, a modified Delphi procedure was implemented, and consensus was reached at a threshold of 70% agreement, or 50%+1 when a question required rediscussion.Results:In phase 1, 167 out of 2,200 screened papers provided validated measures of biomarker diagnostic accuracy compared with a gold standard or in predicting progression or conversion of MCI to the dementia stage (i.e., MRI, CSF, FDG-PET, DaT-imaging, amyloid-PET, tau-PET, and myocardial MIBG-scintigraphy and EEG). During phase 2, panelists agreed on the clinical workspace of the workflow, the stage of application, and the patient age window. The workflow is patient-centered and features three levels of assessment (W): W1 defines eleven clinical profiles based on integrated results of neuropsychology, MRI atrophy patterns, and blood tests; W2 describes the first-line biomarkers according to W1 versus clinical suspicion; and W3 suggests the second-line biomarkers when the results of first-line biomarkers are inconsistent with the diagnostic hypothesis, uninformative or inconclusive. CSF biomarkers are first-line in the suspect of Alzheimer’s disease (AD) and when inconsistent neuropsychological and MRI findings hinder a clear diagnostic hypothesis; dopamine SPECT/PET for those leading to suspect Lewy body spectrum. FDG-PET is first-line for the clinical profiles leading to suspect frontotemporal lobar degeneration and motor tauopathies and is followed by CSF biomarkers in the case of atypical metabolic patterns, when an underlying AD etiology is conceivable.Conclusions:The workflow will promote consistency in diagnosing neurocognitive disorders across countries and rational use of resources. The initiative has some limitations, mainly linked to the Delphi procedure (e.g., kickoff questions were driven by the moderators, answers are driven by the Delphi panel composition, a subtle phrasing of the questions may drive answers, and 70% threshold for convergence is conventional). However, the diagnostic workflow will be able to help clinicians achieve an early and sustainable etiological diagnosis and enable the use of disease-modifying drugs as soon as they become available.

Proposed diagnostic criteria for arrhythmogenic cardiomyopathy: European Task Force consensus report

Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease characterized by prominent “non-ischemic” myocardial scarring predisposing to ventricular electrical instability. Diagnostic criteria for the original phenotype, arrhythmogenic right ventricular cardiomyopathy (ARVC), were first proposed in 1994 and revised in 2010 by an international Task Force (TF). A 2019 International Expert report appraised these previous criteria, finding good accuracy for diagnosis of ARVC but a lack of sensitivity for identification of the expanding phenotypic disease spectrum, which includes left-sided variants, i.e., biventricular (ABVC) and arrhythmogenic left ventricular cardiomyopathy (ALVC). The ARVC phenotype together with these left-sided variants are now more appropriately named ACM. The lack of diagnostic criteria for the left ventricular (LV) phenotype has resulted in clinical under-recognition of ACM patients over the 4 decades since the disease discovery. In 2020, the “Padua criteria” were proposed for both right- and left-sided ACM phenotypes. The presently proposed criteria represent a refinement of the 2020 Padua criteria and have been developed by an expert European TF to improve the diagnosis of ACM with upgraded and internationally recognized criteria. The growing recognition of the diagnostic role of CMR has led to the incorporation of myocardial tissue characterization findings for detection of myocardial scar using the late‑gadolinium enhancement (LGE) technique to more fully characterize right, biventricular and left disease variants, whether genetic or acquired (phenocopies), and to exclude other “non-scarring” myocardial disease. The “ring-like’ pattern of myocardial LGE/scar is now a recognized diagnostic hallmark of ALVC. Additional diagnostic criteria regarding LV depolarization and repolarization ECG abnormalities and ventricular arrhythmias of LV origin are also provided. These proposed upgrading of diagnostic criteria represents a working framework to improve management of ACM patients.

Use of omalizumab is associated with improvement of pruritic skin disorders induced by immune checkpoint inhibitors: A retrospective cohort from the European Task Force of Dermatology for Cancer patients

Use of omalizumab is associated with improvement of pruritic skin disorders induced by immune checkpoint inhibitors: A retrospective cohort from the European Task Force of Dermatology for Cancer patients

Clinician-reported outcome measures for the assessment of vitiligo: A scoping review.

Clinician-reported outcome measures (ClinROMs) are essential for assessment of vitiligo in clinical trials and daily practice. Several instruments have been developed and tested to measure, for example, vitiligo extent, repigmentation and activity. The goal of this review was to identify all introductory publications of ClinROMs for vitiligo that include at least some aspects of validation and to describe the instruments' characteristics, intention for use and practical strengths and limitations. A search strategy was conducted in PubMed, Embase and Cochrane Library (CENTRAL) from inception to July 2022. Based on the literature search (n = 2860), 10 articles were identified, describing 14 different ClinROMs. Six ClinRoms measured disease extent and/or repigmentation, seven evaluated disease activity and one was a composite score. The Vitiligo Area Scoring Index (VASI), and Vitiligo Extent Score (VES and VESplus) measure overall disease extent and/or repigmentation. The VASI relies on hand units (1% body surface area), whereas the VES and VESplus use a picture-based scoring technique. The Vitiligo Extent Score for a Target Area (VESTA) measures repigmentation percentage for target lesions. One global assessment score for extent has been validated. Vitiligo disease activity scores included a static measure of clinical activity signs (Vitiligo Signs of Activity Score [VSAS]) and two measures assessing dynamic evolution (Vitiligo Disease Activity Score [VDAS] and Vitiligo Disease Improvement Score [VDIS]). The Vitiligo European Task Force assessment tool (VETFa) is a composite score. Depending on the practical strengths and limitations as well as the research question and setting (clinical trials vs. daily practice), the choice of an appropriate ClinROM may differ. Fourteen ClinROMs in vitiligo were identified to measure vitiligo extent, repigmentation, and activity. Further research evaluating the validity, reliability, and responsiveness of each instrument and worldwide consensus on which instrument to use for a specific outcome (domain) is greatly needed.

P45 An analysis of infantile haemangioma referrals and comparison with the infantile haemangioma European task force’s ‘infantile haemangioma referral score’

Abstract Infantile haemangiomas (IHs) are common. Timely referral and treatment can minimize complications in high-risk lesions. The IH European Task Force developed the Infantile Haemangioma Referral Score (IHRes) in 2020 (Léauté-Labrèze C, Torres EB, Weibel L et al. The Infantile Hemangioma Referral Score: a validated tool for physicians. Pediatrics 2020; 145:e20191628). This is a simple, easy-to-access validated screening tool that can assist physicians in deciding which IHs to refer to an expert centre. The aim of this study was to assess the quality of IH referrals to a national care centre. Data were retrospectively collected from a random sample of patients over a 13-month period between January 2019 and February 2020. Fifty-six patients were included. Eighty-six per cent had a solitary haemangioma (n = 48); 52% of IHs were located on the head (n = 29). Sixteen patients (29%) were referred between 5 and 8 weeks of age (29%); five patients (9%) were referred before 5 weeks of age. The majority of referrals came from primary care (55%; n = 31). Seventy-three per cent of referrers did not specify the urgency of the referrals (n = 41); 59% were subsequently triaged as urgent by a consultant dermatologist (n = 33). Most referrals did not specify the size of the IH (43%; n = 24), if it was actively growing (48%; n = 27), ulcerated (93%; n = 52) or potentially function threatening (84%; n = 47). Nine per cent included a photograph of the lesion (n = 5). Seventy-five per cent of referrals satisfied the IHRes six major criteria or had scores &amp;gt; 4, warranting a referral (n = 42). Fifteen patients (27%) were started on propranolol at first appointment and a further 12 were monitored in a return appointment. Our results show that use of the IHReS tool could improve clinical outcomes by identifying children that require specialist referral earlier and facilitate easier triage of referrals.

European Inter‐Societal Delphi Consensus for the biomarker‐based etiological diagnosis of neurocognitive disorders in the mild stage

AbstractBackgroundCSF and imaging biomarkers are needed for the etiological diagnosis of neurocognitive disorders, but evidence is incomplete on their rational use in the clinic. Since October 2020, a European task force has been defining an evidence‐based diagnostic workflow, where incomplete evidence is filled by the opinion of experts. Herein, we report the preliminary results through January 2022.MethodA Delphi method was used to reach consensus. Eleven pertinent European scientific societies delegated two panelists each to join Delphi rounds and voting. Consensus was set at 70% of consistent responses.ResultIn the 5 voting rounds completed so far, panelists defined clinical setting (specialist outpatient service) and stage of application (prodromal and mild dementia) of the workflow, patients’ age window of biomarkers use (strongly encouraged below 70 years and of limited usefulness over 85). Workflow is configurated to be patient‐centered and structured on three levels of assessment (W): W1, definition of clinical profiles based on the combined results of MRI, neuropsychology, blood tests; W2, choice of first‐line biomarkers according to the main clinical suspicion (i.e., FDG‐PET for frontotemporal lobar degeneration and motor tauopathies, dopamine SPECT/PET for Lewy body spectrum disorders, and CSF biomarkers either for Alzheimer’s disease or in cases with inconclusive neuropsychological and/or MRI findings, whereas no biomarker was indicated in suspected vascular cognitive impairment); W3, selection of a second‐line biomarker when results of first‐line biomarkers are inconsistent with diagnostic hypothesis (i.e., not typical FDG‐PET pattern) or uninformative (i.e., borderline CSF amyloid results) or not sufficient to rule out other etiologies (i.e., amyloid‐positive and tau‐negative CSF results) or when a diagnosis remains possible despite a negative first‐line biomarker (e.g., normal dopamine SPECT/PET in suspected prodromal dementia with Lewy bodies).ConclusionThe task force is currently defining the second‐line biomarkers of W3 and the project it set to deliver the final algorithm by June 2022. The workflow will promote consistency in diagnosing neurocognitive disorders across countries, and rational use of resources. The initiative has an impact in preparing clinicians to work in the upcoming clinical space where etiological disease‐modifying drugs are expected to be available.

Long-term durability of self-expanding and balloon-expandable transcatheter aortic valve prostheses: UK TAVI registry.

With expansion of transcatheter aortic valve implantation (TAVI) into younger patients, valve durability is critically important. We aimed to evaluate long-term valve function and incidence of severe structural valve deterioration (SVD) among patients ≥ 10-years post-TAVI and with echocardiographic follow-up at least 5-years postprocedure. Data on patients who underwent TAVI from 2007 to 2011 were obtained from the UK TAVI registry. Patients with paired echocardiograms postprocedure and ≥5-years post-TAVI were included. Severe SVD was determined according to European task force guidelines. 221 patients (79.4 ± 7.3 years; 53% male) were included with median echocardiographic follow-up 7.0 years (range 5-13 years). Follow-up exceeded 10 years in 43 patients (19.5%). Valve types were the supra-annular self-expanding CoreValve (SEV; n = 143, 67%), balloon-expandable SAPIEN/XT (BEV; n = 67, 31%), Portico (n = 4, 5%) and unknown (n = 7, 3%). There was no difference between postprocedure and follow-up peak gradient in the overall cohort (19.3 vs. 18.4 mmHg; p = NS) or in those with ≥10-years follow-up (21.1 vs. 21.1 mmHg; p = NS). Severe SVD occurred in 13 patients (5.9%; median 7.8-years post-TAVI). Three cases (23.1%) were due to regurgitation and 10 (76.9%) to stenosis. Valve-related reintervention/death occurred in 5 patients (2.3%). Severe SVD was more frequent with BEV than SEV (11.9% vs. 3.5%; p = 0.02), driven by a difference in patients treated with small valves (BEV 28.6% vs. SEV 3.0%; p < 0.01). Hemodynamic function of transcatheter heart valves remains stable up to more than 10 years post-TAVI. Severe SVD occurred in 5.9%, and valve-related death/reintervention in 2.3%. Severe SVD was more common with BEV than SEV.

Working up the six-pack: Bargaining success in the European Council's task force on strengthening economic governance

This article assesses the factors associated with member states’ bargaining success during the negotiations in the European Council's 2010 task force on strengthening economic governance, the pre-decision stage for the Six-Pack. We test theories of decision-making based on the expertise of institutions, and EU member states’ preferences and power resources using new data. With methods derived from the decision-making in the EU projects, we find that proximity to the European Central Bank was associated with greater bargaining success for member states and that the opposite was the case for closeness to the Commission's preferences. We find mixed evidence that member states’ level of indebtedness is associated with bargaining success, defined as the minimum distance between the position of a member state and the final outcome. The findings indicate the importance of the ECB's role given its technical expertise, in defining the outcomes of the task force.

Dementia prevention in memory clinics: recommendations from the European task force for brain health services.

Observational population studies indicate that prevention of dementia and cognitive decline is being accomplished, possibly as an unintended result of better vascular prevention and healthier lifestyles. Population aging in the coming decades requires deliberate efforts to further decrease its prevalence and societal burden. Increasing evidence supports the efficacy of preventive interventions on persons with intact cognition and high dementia risk. We report recommendations for the deployment of second-generation memory clinics (Brain Health Services) whose mission is evidence-based and ethical dementia prevention in at-risk individuals. The cornerstone interventions consist of (i)assessment of genetic and potentially modifiable risk factors including brain pathology, and risk stratification, (ii) risk communication with ad-hoc protocols, (iii) risk reduction with multi-domain interventions, and (iv) cognitive enhancement with cognitive and physical training. A roadmap is proposed for concept validation and ensuing clinical deployment.