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Although sudden cardiac death (SCD) is one of the most important modes of death in Western countries, pathologists and public health physicians have not given this problem the attention it deserves. New methods of preventing potentially fatal arrhythmias have been developed and the accurate diagnosis of the causes of SCD is now of particular importance. Pathologists are responsible for determining the precise cause and mechanism of sudden death but there is still considerable variation in the way in which they approach this increasingly complex task. The Association for European Cardiovascular Pathology has developed these guidelines, which represent the minimum standard that is required in the routine autopsy practice for the adequate investigation of SCD. The present version is an update of our original article, published 10 years ago. This is necessary because of our increased understanding of the genetics of cardiovascular diseases, the availability of new diagnostic methods, and the experience we have gained from the routine use of the original guidelines. The updated guidelines include a detailed protocol for the examination of the heart and recommendations for the selection of histological blocks and appropriate material for toxicology, microbiology, biochemistry, and molecular investigation. Our recommendations apply to university medical centers, regionals hospitals, and all healthcare professionals practicing pathology and forensic medicine. We believe that their adoption throughout Europe will improve the standards of autopsy practice, allow meaningful comparisons between different communities and regions, and permit the identification of emerging patterns of diseases causing SCD. Finally, we recommend the development of regional multidisciplinary networks of cardiologists, geneticists, and pathologists. Their role will be to facilitate the identification of index cases with a genetic basis, to screen appropriate family members, and ensure that appropriate preventive strategies are implemented.

Although sudden cardiac death (SCD) is one of the most important modes of death in Western countries, pathologists and public health physicians have not given this problem the attention it deserves. New methods of preventing potentially fatal arrhythmias have been developed and the accurate diagnosis of the causes of SCD is now of particular importance. Pathologists are responsible for determining the precise cause and mechanism of sudden death but there is still considerable variation in the way in which they approach this increasingly complex task. The Association for European Cardiovascular Pathology has developed these guidelines, which represent the minimum standard that is required in the routine autopsy practice for the adequate investigation of SCD. The present version is an update of our original article, published 10 years ago. This is necessary because of our increased understanding of the genetics of cardiovascular diseases, the availability of new diagnostic methods, and the experience we have gained from the routine use of the original guidelines. The updated guidelines include a detailed protocol for the examination of the heart and recommendations for the selection of histological blocks and appropriate material for toxicology, microbiology, biochemistry, and molecular investigation. Our recommendations apply to university medical centers, regionals hospitals, and all healthcare professionals practicing pathology and forensic medicine. We believe that their adoption throughout Europe will improve the standards of autopsy practice, allow meaningful comparisons between different communities and regions, and permit the identification of emerging patterns of diseases causing SCD. Finally, we recommend the development of regional multidisciplinary networks of cardiologists, geneticists, and pathologists. Their role will be to facilitate the identification of index cases with a genetic basis, to screen appropriate family members, and ensure that appropriate preventive strategies are implemented.

Telethon Associazione Serena Talarico per i giovani nel mondo and Fondazione Giuseppe Tomasello O.N.L.U.S. Mitocon Onlus Research to Prevent Blindness International Foundation for Optic Nerve Diseases (IFOND) Struggling Within Leber's Poincenot Family Eierman Foundation National Eye Institute Leber's hereditary optic neuropathy is a maternally inherited blinding disease caused as a result of homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. It is characterized by incomplete penetrance, as only some mutation carriers become affected. Thus, the mitochondrial DNA mutation is necessary but not sufficient to cause optic neuropathy. Environmental triggers and genetic modifying factors have been considered to explain its variable penetrance. We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber's hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. We show that unaffected mutation carriers have a significantly higher mitochondrial DNA copy number and mitochondrial mass compared with their affected relatives and control individuals. Comparative studies of fibroblasts from affected, carriers and controls, under different paradigms of metabolic demand, show that carriers display the highest capacity for activating mitochondrial biogenesis. Therefore we postulate that the increased mitochondrial biogenesis in carriers may overcome some of the pathogenic effect of mitochondrial DNA mutations. Screening of a few selected genetic variants in candidate genes involved in mitochondrial biogenesis failed to reveal any significant association. Our study provides a valuable mechanism to explain variability of penetrance in Leber's hereditary optic neuropathy and clues for high throughput genetic screening to identify the nuclear modifying gene(s), opening an avenue to develop predictive genetic tests on disease risk and therapeutic strategies. Univ Rome, Dept Radiol Oncol & Pathol, Rome, Italy Univ Bologna, Dept Biomed & NeuroMotor Sci DIBINEM, Bologna, Italy Univ Bari, Dept Biosci Biotechnol & Biopharmaceut, Bari, Italy Bellaria Hosp, IRCCS Ist Sci Neurol Bologna, I-40139 Bologna, Italy USC, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA USA USC, Keck Sch Med, Dept Neurosurg, Los Angeles, CA USA Univ Trieste, Dept Reprod Sci Dev & Publ Hlth, Trieste, Italy Univ Trieste, IRCCS Burlo Garofolo Children Hosp, Trieste, Italy Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England Fdn Ist Neurol Carlo Besta IRCCS, Unit Mol Neurogenet, Milan, Italy MRC Mitochondrial Biol Unit, Cambridge, England Fed Univ São Paulo UNIFESP, Dept Ophthalmol, São Paulo, Brazil Univ São Paulo, Inst Psychol, Dept Expt Psychol, São Paulo, Brazil Studio Oculist dAzeglio, Bologna, Italy Osped San Giovanni Evangelista, Tivoli, Italy Azienda Osped San Camillo Forlanini, Rome, Italy Univ Rome, Dipartimento Metodi & Modelli Econ Finanza & Terr, Rome, Italy Univ Rome, Dept Mol Med, Rome, Italy Fed Univ São Paulo UNIFESP, Dept Ophthalmol, São Paulo, Brazil Telethon: GGP06233 Telethon: GGP11182 Telethon: GPP10005 National Eye Institute: EY03040 Web of Science

Multimodal imaging plays a pivotal role in the assessment of the thoracic aorta, both in chronic and acute settings. Moving from improved knowledge on the structure and function of the aortic wall, as well as on its pathophysiology and histopathology, appropriate utilization of each imaging modality results into a better definition of the patient's need and proper treatment strategy. This review is aimed at highlighting the most critical aspects in this field, providing cardiologists with some novel clues for the imaging approach to patients with thoracic aortic disease. © 2014 Il Pensiero Scientifico Editore.

The Italian Scientific Associations of Cardiologists and Cardiovascular Pathologists have produced this consensus document on the diagnostic role of endomyocardial biopsy (EMB) in terms of techniques, analysis and reporting. The document is intended for clinical cardiologists, hemodynamic experts, electrophysiologists, surgical pathologists, and cardiac surgeons. It has three main aims: a) to collocate EMB in the context of currently available tools for diagnosis of heart diseases; b) to provide recommendations for rational implementation; c) to outline key characteristics (standards) for Italian cardiology and surgical pathology centers that perform and analyze EMB. A general lack of prospective, controlled studies addressing EMB prohibited the use of traditional evidence-based recommendations that rely on classes of available evidence. Thus, it was agreed that three key points should be taken into account: a) the specific pathology to be diagnosed (or excluded); b) the existence of any alternative, non-invasive diagnostic techniques; c) the overall consequences of reaching a definite diagnosis on patients' clinical management. Accordingly, we propose recommendations for EMB based on the following levels of diagnostic value: level 1: no alternative method exists to reach a definite diagnosis that can have obvious consequences for clinical management; level 2a: no alternative method exists to reach a definite diagnosis; however, the implications for clinical management are uncertain; level 2b: no alternative method exists to reach a definite diagnosis; however, the diagnosis would not influence clinical management; level 3: an alternative method exists to reach a definite diagnosis. The second part of the document proposes current protocols for the preparation, analysis and reporting of EMB in the context of each main pathologic entity. Particular attention is given to tissue characterization and implementation of molecular tests.

Which queries stand to gain or loose from diversifying their results?Some queries are more difficult than others for diversification. Across a numberof conceptually different diversification methods, performance on such queriestends to deteriorate after applying these diversification methods, even though theirinitial performance in terms of relevance or diversity tends to be good.

Ragionevoli certezze. Le recenti acquisizioni in tema di patologia aortica devono indurre a riconsiderare il work-up diagnostico delle aortopatie, alla luce della complessità dei loro substrati istopatologici, genetici, biomolecolari e fisiopatologici. Questioni aperte. L’inquadramento diagnostico delle aortopatie non può prescindere da una valutazione clinica “sistemica” (malattie genetiche del connettivo, malattie metaboliche, malattie sistemiche su base immune) e deve avvalersi dello studio approfondito con le tecniche di imaging, non più esclusivamente limitato al rilievo del diametro aortico, ma arricchito dalla valutazione di parametri morfologici più dettagliati e funzionali. Le ipotesi. La conoscenza della fisiopatologia aortica può fornire elementi utili sia per la gestione del singolo paziente con malattia aortica e/o cardiaca che per la stratificazione prognostica, e potrebbe consentire in un prossimo futuro anche l’individuazione di nuovi target terapeutici.

Nowadays, the histopathological study of surgical specimens is an essential part of the diagnostic work-up in aortic disease, and not only in characterizing the neoplastic forms. Despite increasing clinico-therapeutic complexity of aortic pathology, the criteria for histopathological diagnosis have not been properly updated over the years, with the result that we find inconsistent terminology and little standardization of diagnostic criteria. In light of this consideration, the SIAPeC-IAP Study Group of "Cardiovascular Pathology", in collaboration with the Association for Italian Cardiovascular Pathology, has created this consensus document, with the aim of defining the features of histopathological substrates in the main non-neoplastic aortopathies (atherosclerotic, "degenerative"/non inflammatory, and inflammatory) and of systematizing diagnostic criteria even for the rare tumours of the aorta and pulmonary artery. The principal aims of the project are defining histopathological diagnostic criteria, standard nomenclature and classification, methodology and reporting of histopathological study and handling of aortic specimens. In addiction, some current issues and new knowledge emerging from basic aortic research are debated, with the aim of promoting a "modern" and up-to-date view of aortic pathology.

Multimodal imaging plays a pivotal role in the assessment of the thoracic aorta, both in chronic and acute settings. Moving from improved knowledge on the structure and function of the aortic wall, as well as on its pathophysiology and histopathology, appropriate utilization of each imaging modality results into a better definition of the patient's need and proper treatment strategy. This review is aimed at highlighting the most critical aspects in this field, providing cardiologists with some novel clues for the imaging approach to patients with thoracic aortic disease.