Application of Precision Medicine in Neurodegenerative Diseases

One of the main challenges for healthcare systems is the increasing prevalence of neurodegenerative pathologies together with the rapidly aging populations. The enormous progresses made in the field of biomedical research and informatics have been crucial for improving the knowledge of how genes, epigenetic modifications, aging, nutrition, drugs and microbiome impact health and disease. In fact, the availability of high technology and computational facilities for large-scale analysis enabled a deeper investigation of neurodegenerative disorders, providing a more comprehensive overview of disease and encouraging the development of a precision medicine approach for these pathologies. On this subject, the creation of collaborative networks among medical centers, research institutes and highly qualified specialists can be decisive for moving the precision medicine from the bench to the bedside. To this purpose, the present review has been thought to discuss the main components which may be part of precise and personalized treatment programs applied to neurodegenerative disorders. Parkinson Disease will be taken as an example to understand how precision medicine approach can be clinically useful and provide substantial benefit to patients. In this perspective, the realization of web-based networks can be decisive for the implementation of precision medicine strategies across different specialized centers as well as for supporting clinical/therapeutical decisions and promoting a more preventive and participative medicine for neurodegenerative disorders. These collaborative networks are essentially addressed to find innovative, sustainable and effective strategies able to provide optimal and safer therapies, discriminate at risk individuals, identify patients at preclinical or early stage of disease, set-up individualized and preventative strategies for improving prognosis and patient's quality of life

La diagnosi di annegamento: un'autopsia ancora problematica

L’annegamento è un fenomeno a bassa incidenza ma con elevata mortalità, risultando essere nel mondo una tra le principali cause di morte accidentale. Inoltre, non raramente, l’annegamento viene usato con finalità suicidiaria od omicidiaria, assumendo quindi una corretta diagnosi medico-legale un ruolo risolutivo, soprattutto in caso di permanenza in acqua del cadavere per periodi di tempo anche lunghi. L’indagine su corpi recuperati in acqua dunque comprende una quota importante dei compiti del medico-legale che con l’avanzare delle conoscenze scientifiche, specialmente nel campo della biologia molecolare e dell’immunoistochimica, può avvalersi sempre di nuove metodiche di indagine senza dover abbandonare le precedenti: un’attenta ispezione della scena del ritrovamento del cadavere ed un accurato esame autoptico devono essere completati da indagini tossicologiche e di laboratori

A data mining approach to investigate patterns of powered two-wheeler crashes in Spain

Powered two-wheelers (PTWs) are growing globally each year as they are considered an attractive alternative to cars (flexible, small, affordable, fast and easy to park), especially on congested traffic situations. However, PTWs represent an important challenge for road safety. In fact, in 2016, Spain ranked fifth in terms of PTW fatalities among EU 28. For this reason, this paper aims to investigate which are the patterns among crash characteristics contributing to PTW crashes in Spain. Data from 78,611 crashes involving PTWs occurred in Spain in the period 2011–2013 were analyzed. The analysis was performed by using classification trees and rules discovery which are suitable models aimed at extracting knowledge and identifying valid and understandable patterns from large amounts of data previously unknown and indistinguishable. The response variables assessed in this study were severity and crash type. As a result, several combinations of road, environmental and drivers’ characteristics associated with severity and typology of PTW crashes in Spain were identified. Based on the analysis results, several countermeasures to solve or mitigate the safety issues identified in the study were proposed. From the methodological point of view, study results show that both the classification trees and the a priori algorithm were effective in providing non-trivial and unsuspected relations in the data. Classification trees structure allowed a simpler understanding of the phenomenon under study while association discovery provided new information which was previously hidden in the data. Given that the results of the two different techniques were never contradictory, we recommend using classification trees and association discovery as complementary approaches since their combination is effective in exploring data providing meaningful insights about PTW crash characteristics and their interdependencies

A fatal case of intoxication after an unsuspected combined intake of verapamil and atenolol.

Calcium channel blockers (CCBs) and ß-blockers are used, combined or individually, in the treatment of hypertension, angina pectoris, cardiac arrhythmias, and other disorders. However, cardiogenic shock has been reported as a rare complication associated with the combination of verapamil and ß-blockers that can be resolved by medical intervention. We describe the case of a 35-year-old woman who developed a fatal cardiogenic shock after an unintentional overdose of verapamil (calcium channel blocker) and atenolol (ß-blocker) that was discovered only after autopsy and toxicological analyses

A Rapid Fatal Outcome of Iliopsoas Hematoma: Clinical and Autopsy Findings

A case of massive muscular bleeding of iliopsoas resulting in lethal exsanguination is presented. The intramuscular bleeding occurred spontaneously in an old man with heart failure, presented to the emergency department after the acute onset of shortness of breath, and treated with therapeutic doses of antiplatelets and heparin to prevent thrombosis. On the sixth day of recovery, pain in the left lumbar region develops while there was a decrease in hemoglobin level. Computed tomography (CT) scan revealed a 10 × 3 cm hematoma of the left iliac muscle. The treatment was immediately stopped, but within 6 hours, the death was confirmed. The autopsy revealed that the hematoma, and its increased size since the latest imaging assessment, was the leading cause of death. Particularly in older patients with comorbidity, even in those with clotting parameters in the therapeutic range, the potential for fatal result of iliopsoas muscle bleeding should be considered. Identifying potential patience with increased risk of this complication could be important, especially in pandemic time of COVID-19, when the use of anticoagulant therapy—both for treatment and for prevention of severe disease—has become massive and addressed also to people without previous and specific pathologies

Application of Precision Medicine in Neurodegenerative Diseases

One of the main challenges for healthcare systems is the increasing prevalence of neurodegenerative pathologies together with the rapidly aging populations. The enormous progresses made in the field of biomedical research and informatics have been crucial for improving the knowledge of how genes, epigenetic modifications, aging, nutrition, drugs and microbiome impact health and disease. In fact, the availability of high technology and computational facilities for large-scale analysis enabled a deeper investigation of neurodegenerative disorders, providing a more comprehensive overview of disease and encouraging the development of a precision medicine approach for these pathologies. On this subject, the creation of collaborative networks among medical centers, research institutes and highly qualified specialists can be decisive for moving the precision medicine from the bench to the bedside. To this purpose, the present review has been thought to discuss the main components which may be part of precise and personalized treatment programs applied to neurodegenerative disorders. Parkinson Disease will be taken as an example to understand how precision medicine approach can be clinically useful and provide substantial benefit to patients. In this perspective, the realization of web-based networks can be decisive for the implementation of precision medicine strategies across different specialized centers as well as for supporting clinical/therapeutical decisions and promoting a more preventive and participative medicine for neurodegenerative disorders. These collaborative networks are essentially addressed to find innovative, sustainable and effective strategies able to provide optimal and safer therapies, discriminate at risk individuals, identify patients at preclinical or early stage of disease, set-up individualized and preventative strategies for improving prognosis and patient's quality of lif

Antigenicity Preservation Is Related to Tissue Characteristics and the Post-Mortem Interval: Immunohistochemical Study and Literature Review

The main aim of this study was to investigate the post-mortem proteolytic degradation process of selected tissue antigens and correlate it to the post-mortem interval. During the autopsy of 12 cadavers (time interval ranging 1 day–2 years after death) samples of skin, liver, kidney, and spleen were collected. All samples were formalin-fixed and paraffin-embedded. Four µm paraffin sections were used for hematoxylin–eosin staining and immunohistochemical analysis (Ki67, Vimentin, Pan cytokeratin, and CD20). Data reported here show that immunohistochemical reactivity preservation was related to the characteristics of the tissues. In particular, the most resistant tissue was the skin, where the autolysis phenomena were not appreciable before 5 days. On the contrary, the liver and the spleen underwent early autolysis, while the kidney displayed an early autolysis of the tubules and a late one of the glomeruli. As concerns specific antigens, immunoreactivity was lost earliest for nuclear antigens as compared to cytoplasmic ones. In conclusion, our results demonstrate that immunohistochemical detection of specific antigens may be useful in estimating the post-mortem interval, especially when we need to know whether the post-mortem interval is a few days or more than 7–10 days