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    Stima dell’età ossea sul vivente a scopo forense mediante analisi dei nuclei di ossificazione del carpo su Imaging a Risonanza Magnetica

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    Negli ultimi anni le indagini scientifiche volte alla stima dell’età hanno ampliato notevolmente i loro orizzonti, dal cadavere al vivente. Riguardo ai viventi, detto accertamento viene richiesto per diversi ambiti: nelle procedure di adozione, nel contesto di competizioni sportive agonistiche, in tema di immigrazione e nella tutela di minori non accompagnati, per scopi forensi come per l’imputabilità minorile o nell’accertamento del reato di pedopornografia. Nel fornire il dato scientifico, il medico-legale deve tener conto di fattori di variabilità legati all’etnia o alla razza, alle condizioni ambientali, alle diversità di maturazione scheletrica insita in ogni individuo, alle eventuali patologie preesistenti. Da qui il difficile compito di fornire al Giudice il risultato nella maniera più facilmente intellegibile, possibilmente in maniera numerica e con indicazioni statistiche, con evidenza di margine di errore e cut-off. Nei soggetti in crescita gli indicatori maggiormente utilizzati per la determinazione dell’età sono quelli che permettono la valutazione della maturità sessuale, della maturità scheletrica e della maturità dentaria. Pur non essendoci procedure univocamente riconosciute, attualmente i metodi maggiormente utilizzati prevedono un esame fisico e un’analisi antropometrica, un’analisi dentale ortopantomografica (OPT) e uno studio rx di mano e polso sinistri. Per i minori l’accertamento dell’età evoca delle problematiche di carattere etico, laddove sia prevista da molti protocolli operativi l’utilizzazione di radiazioni ionizzanti. Dalle organizzazioni internazionali per la tutela dei minori è stato in più circostanze rimarcato che non può considerarsi eticamente corretto sottoporre un soggetto in crescita ad analisi tramite raggi x in assenza di motivazioni cliniche alla base dell’accertamento. In questo scenario, diversi studi di epoca recente hanno approfondito il possibile utilizzo di esami che non prevedono erogazione di radiazioni ionizzanti in materia di determinazione dell’età, come la Risonanza Magnetica Nucleare (RMN). L’impiego della RMN su regioni anatomiche indagate da tempo mediante esami radiografici è legato alla necessità di dover confrontare i risultati con i dati già esistenti per la stima dell’età. Questo è il motivo per cui il polso e la mano sinistra, così come l’estremità sternale della clavicola, sono stati oggetto di studi scientifici con tecniche di RMN; sono stati altresì oggetto di indagine regioni anatomiche scarsamente visualizzabili mediante esami rx, come l’epifisi tibiale distale e calcaneare, nonché l’epifisi tibiale prossimale e femorale distale. L’analisi mediante RM sulla regione carpale per la stima dell’età è stata presentata in pochi lavori, alcuni dei quali hanno preso in considerazione lo sviluppo delle ossa del carpo congiuntamente alla maturazione delle ossa tubulari del polso, vale a dire ulna e radio. Le otto ossa del carpo vanno incontro ad un processo di ossificazione endocondrale, ciascuna da un solo centro; primo è il capitato e ultimo il pisiforme, il quale inizia a ossificare nel 9°-10° anno nelle femmine e nel 12° nei maschi. L’ordine di ossificazione delle altre ossa è soggetto a variazioni legate al sesso, all’alimentazione, alla razza; l’ossificazione si rende completa solamente tra i 20 e i 24 anni. Il progressivo accrescimento dei nuclei di ossificazione carpali in minori adolescenti è accompagnato, oltre che da una riduzione progressiva dello strato di cartilagine periossea, anche da una riduzione dello spazio lacunare (interfaccia) formatosi tra il nucleo osseo e la cartilagine periossea. Lo scopo del nostro progetto è stato quello di realizzare un modello per la stima dell’età basandoci sul rapporto tra l’area occupata dal nucleo di ossificazione (“Nucleus of ossification” - NO) e l’area totale derivante dal nucleo di ossificazione + lo spazio lacunare compreso tra il nucleo stesso e la cartilagine periossea ( “Surface of growth” – SG). In collaborazione con la SOD Radiologia Pediatrica e Specialistica di AOU - Ospedali Riuniti di Ancona, è stato eseguito uno studio retrospettivo osservazionale: sono stati selezionati 40 soggetti di nazionalità italiana (21 femmine e 19 maschi) con un range di età compreso tra i 12 e i 20 anni, sottoposti a RM di mano sinistra nel periodo 2012-2018. I soggetti erano privi di patologie legate a disturbi di accrescimento osseo. Lo strumento utilizzato è stato lo stesso per tutti i soggetti: una RMN aperta da 1,5 T (Philips Achieva). L’immagine RM di ciascuno osso carpale, estrapolata mediante l’ausilio di specialista radiologo, è stata analizzata mediante il software ImageJ, con il quale è stata dapprima selezionata l’area NO, e successivamente l’area totale SG. Detto procedimento è stato ripetuto per ciascuno osso carpale e i dati memorizzati per intero dal software, sono stati poi salvati in un file in formato excel. Ottenute le aree NO e SG di ogni singolo osso, si è proceduto a calcolare il rapporto tra la somma di tutti i NO (NOtot) e la somma di tutte le SG (SGtot) delle 8 ossa (NOSGtot). Detta procedura è stata ripetuta per ciascuno dei 40 soggetti selezionati. E’ stata stimata la variabilità intra e inter-operatore, con risultati attestanti una buona riproducibilità della metodica. I risultati ottenuti hanno consentito di realizzare un modello di regressione lineare con la seguente equazione: età= α+β∙〖NOSG〗_tot+γ∙sex+ε Dove sex=1 se maschio, 0 se è femmina ed è l’errore casuale con distribuzione normale, media 0 e varianza 2. I parametri del modello, , e , sono stati stimati mediante il metodo dei minimi quadrati. La stima dell’errore standard è risultata 0.28 anni. Il valore del coefficiente di determinazione della regressione è stato R2 = 0.988, indicando un ottimo adattamento del modello ai dati. Il metodo andrà testato su più ampie casistiche e su diversi gruppi etnici. In combinazione con altre tecniche, il modello elaborato potrà in un futuro essere applicato per scopi forensi.In recent years, scientific surveys for age estimation have greatly expanded their horizons, from the cadaver to the living. Regarding the living, this kind of verification is required for different areas: in adoption procedures, in the context of sporting competitions, about immigration, in the protection of unaccompanied minors, for forensic purposes such as for child offense or in the ascertainment of the crime of child pornography. In providing the scientific data, the forensic physician must consider variability factors related to ethnicity or race, environmental conditions, diversity of skeletal maturation of each individual, pre-existing pathologies. Hence the difficult task of providing the result in the most easily intelligible way for the judge, possibly in a numerical way and with statistical indications, highlighting the margin of error and cut-off. In the growing subjects the most used indicators for the forensic age determination are linked to the evaluation of sexual maturity, skeletal maturity and dental maturity. Although there are no univocally recognized procedures, currently the most used methods include a physical examination and anthropometric analysis, an orthopantomographical analysis and a left hand and wrist x-ray study. For minors, age assessment evokes ethical issues, with regard to the use of radiation as well as recommended by many operational protocols. The international organizations for the protection of minors have underlined in more circumstances that it can not be considered ethically correct to expose a minor to x-ray analysis in the absence of clinical reasons. In this scenario, several recent studies have investigated the possible use of exams in the field of age determination that do not provide ionizing radiation, such as Nuclear Magnetic Resonance (NMR). The use of NMR on regions investigated through x-ray exams is linked to the need to compare the results with existing data for age estimation. This is the reason why the wrist and the left hand, as well as the sternal extremity of the clavicle, have been investigated using NMR techniques. Anatomical regions that are poorly visualized by x-ray exams, such as the distal tibial and calcaneal epiphysis, as well as the proximal tibial epiphysis and distal femoral, were also investigated. The analysis of the carpal region by NMR for age estimation has been presented in a few works, some of which have considered the development of carpal bones together with the maturation of ulna and radius. The eight carpal bones undergo an endochondral ossification process, each from a single center; capitate is the first whereas the pisiform is the last to appear and it begins to ossify at the age of 9-10 years in females and 12 years in males. The order of ossification of the other bones is variable and depending on sex, food, race; ossification is complete only between 20 and 24 years. The progressive growth of the carpal ossification nucleus in adolescents is accompanied, both by a progressive reduction of the external cartilage layer and a reduction of the interface area located between the bone nucleus and the external cartilage. The aim of our project was to create a model for the age estimation based on the ratio between the area occupied by the nucleus of ossification (NO) and the surface of growth deriving from the NO + the interface area (SG). An observational retrospective study was carried out in collaboration with the Pediatric and Specialistic Radiology Departement of AOU - Ospedali Riuniti di Ancona: 40 Italian subjects were selected (21 females and 19 males) in a range between 12 and 20 years, undergoing left-hand NMR in the period 2012-2018. The subjects were free from any bone growth disorders. The instrument used was the same for all subjects: a 1.5 T open NMR (Philips Achieva). The NMR image of each carpal bone, extrapolated with the help of a radiologist, it was analyzed using the ImageJ software, through which the NO and the SG were selected. This procedure was repeated for each carpal bone and the full data were saved in a file in excel format. Once the NO and the SG of each bone were obtained, we calculated the ratio between the sum of all the NO (NOtot) and the sum of all SG (SGtot) of the all 8 bones (NOSGtot). This procedure was repeated for each of the 40 subjects. The intra and inter-operator variability was estimated; the results attesting a good reproducibility of the method. The results obtained allowed to realize a linear regression model with the following equation: age= α+β∙〖NOSG〗_tot+γ∙sex+ε Where sex = 1 for male, 0 for female and is the random error with normal distribution, mean 0 and variance 2. The parameters of the model, , and , were estimated using the least squares method. The estimated standard error was 0.28 years. The value of the regression determination coefficient was R2 = 0.988, indicating an optimal adaptation of the model to the data. The method will be tested on a wider number of cases and on different ethnic groups. In combination with other techniques, the model developed may be applied for forensic purposes in the future

    Eccezioni penali rispetto alle procedure vaccinali

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    Il D.L. n. 44/2021 all’art. 3 interviene sulla responsabilità penale da somministrazione del vaccino anti SARS-CoV-2, sollevando il personale sanitario dalla punibilità quando l’uso del vaccino è conforme alle indicazioni contenute nel provvedimento di autorizzazione all’immissione in commercio e alle circolari pubblicate nel sito istituzionale del Ministero della Salute. Pur dovendo dare atto come nell’attuale contesto di campagna vaccinale difficilmente sono ipotizzabili azioni al di fuori delle linee guida e delle raccomandazioni, alcune criticità di modus operandi sono sorte proprio a seguito di cambi repentini delle indicazioni, come nel caso della somministrazione del vaccino AstraZeneca. In ultimo, se da un lato l’art. 3 del D.L. 44/2021 solleva il personale sanitario dalla punibilità, dall’altro non lo esime dalla possibilità di andare incontro ad un procedimento processuale, in quanto solo in sede processuale è possibile accertare l’eventuale nesso di causalità tra infermità/decesso e somministrazione di vaccino

    COVID-19 pulmonary pathology, Ventilator-Induced Lung Injury (VILI), or sepsis-induced Acute Respiratory Distress Syndrome (ARDS)? Healthcare considerations arising from an autopsy case and miny-review

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    Acute respiratory distress syndrome (ARDS) caused by coronavirus disease (COVID-19) is a serious complication that requires early recognition. Autopsy reports or biopsies of the lungs in patients with COVID-19 revealed diffuse alveolar damage (DAD) at different stages; the fibrotic phase is usually associated with long-standing severe disease. Care management of hospitalized patients is not easy, given that the risk of incurring a ventilator-induced lung injury (VILI) is high. Additionally, if the patient develops nosocomial infections, sepsis-induced ARDS should be considered in the study of the pathophysiological processes. We present an autopsy case of a hospitalized patient whose death was linked to COVID-19 infection, with the histopathological pattern of advanced pulmonary fibrosis. After prolonged use of non-invasive and inva- sive ventilation, the patient developed polymicrobial superinfection oh the lungs. After analyzing the individual’s clinical history and pulmonary anatomopathological findings, we consider healthcare issues that should lead to an improvement in diagnosis and to more adequate standards of care management among health professionals

    Artificial intelligence and digital medicine for integrated home care services in Italy: Opportunities and limits

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    Home healthcare in the Italian health system has proven to be an essential factor in adequately responding to the health needs of an increasingly aging population. The opportunities offered by digitization and new technologies, such as artificial intelligence (AI) and robotics, are a lever for making home care services more effective and efficient on the one hand, and on the other for improving remote patient monitoring. Telemedicine devices have enormous potential for telemonitoring and telerehabilitation of patients suffering from chronic disabling diseases; in particular, AI systems can now provide very useful managerial and decision-making support in numerous clinical areas. AI combined with digitalization, could also allow for the remote monitoring of patients' health conditions. In this paper authors describe some digital and healthcare tools or system of AI, such as the Connected Care model, the Home Care Premium (HCP) project, The Resilia App and some professional service robotics. In this context, to optimize potential and concrete healthcare improvements, some limits need to be overcome: gaps in health information systems and digital tools at all levels of the Italian National Health Service, the slow dissemination of the computerized medical record, issues of digital literacy, the high cost of devices, the poor protection of data privacy. The danger of over-reliance on such systems should also be examined. Therefore the legal systems of the various countries, including Italy, should indicate clear decision-making paths for the patient

    Analysis of immunohistochemical expression of inducible nitric oxide synthase for the evaluation of agonal time in forensic medicine

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    Although establishing agony is crucial in forensic practice, the identification of specific signs indicative of a detailed duration of agony is however not of immediate execution. Nitric oxide (NO) is the most important messenger molecule in the modulation of vascular tone and it is produced during stress conditions by inducible nitric oxide synthase (iNOS), as occurs during agony. The aim of this study was to investigate the relationship between immunohistochemical expression of iNOS, and agonal time (T), defined as the interval between the onset of a hypoxic-ischemic injury and the death. INOS expression was evaluated by measuring the average of signal intensity (SI) from cytoplasm of 300 smooth muscle cells of sample of renal artery, performed by ImageJ software: high values of SI correspond to a low enzyme expression and vice versa. We aimed also to check if gender, age, type of death (violent or natural death), post mortem interval, and storage in cold chamber influenced SI. We assessed 50 autopsied cases, of which 28 violent and 22 natural deaths, with a well-known T in a range between 1 and 631 min. Statistical analysis was performed to estimate the relationship between SI and the other variables. Results pointed out that only SI is related to T, and since data showed a bi-phase relationship between T and SI, we used a piecewise regression method for estimation of T as function of SI. The transition from the first to the second phase takes place at SI = 117.5 which corresponds to a T of 29.5 min. In conclusion, the study demonstrates that iNOS is a good marker for estimating T and the final regression model can be used in many forensic activities

    Multiple sites of thrombosis without thrombocytopenia after a second dose of Pfizer-BioNTech COVID-19 vaccine

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    In the current international scientific panorama, rare cases of venous thrombotic complications following mRNA vaccine administration have been reported, consisting mainly of cerebral sinus thromboses and acute venous thromboembolism. The present paper describes the case of a 75-year-old woman in good health who developed cerebral venous thrombosis, deep venous thrombosis, and bilateral pulmonary emboli after receiving a second dose of Pfizer-BioNTech COVID-19 vaccine. A series of laboratory tests performed during hospitalization yielded interesting results, allowing us to exclude thrombophilic risk factors and to certify the absence of thrombocytopenia in the patient. Although COVID-19 vaccination is the most important tool in stopping the pandemic, pharmacovigilance is crucial for detecting potential multisystem thrombotic events, even for mRNA vaccines

    The Network of Services for COVID-19 Vaccination in Persons With Mental Disorders: The Italian Social Health System, Its Organization, and Bioethical Issues

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    The adoption of restrictive measures aimed at curtailing the spread of SARS-CoV2 has had a harmful impact on socio-affective relationships, while limiting the scope of interventions and activities to promote social inclusion, with considerable negative repercussions for patients with mental disorders. Vaccination has been and will continue to be a valid tool to overcome the barriers of social isolation and to protect the health of this category of patients. In this paper we present an overview of the Italian network of social and healthcare services for COVID-19 vaccination among patients with mental disorders. Some aspects of medical ethics are discussed in order to share good practices for improving the health of this vulnerable group of people. We then consider the measures implemented by the health system in Italy to deal with the phenomenon of vaccine hesitancy before addressing the issue of autonomy and restricted access to vaccination points. Finally, we illustrate some of the perspectives already adopted by the Italian system, which may be useful to the global scientific community

    The State of Play on COVID-19 Vaccination in Pregnant and Breastfeeding Women: Recommendations, Legal Protection, Ethical Issues and Controversies in Italy

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    To date, extensive research has been conducted on vaccination against COVID-19 during pregnancy to verify the safety and efficacy of the vaccines, despite the fact that pregnant women were excluded from the initial clinical trials. The ever-increasing number of scientific publications has confirmed the absence of biological mechanisms associating mRNA vaccines with adverse effects in pregnancy and breastfeeding, although few studies have been carried out on their effect on fertility. While the Italian legal system provides for maternity protection measures and indemnity for vaccination damages pursuant to law no. 210/1992, it is not exempt from controversy. This contribution describes the state of play on COVID-19 vaccination in pregnant and lactating women, including: current recommendations for pregnant and lactating women; ethical issues related to vaccination hesitancy among pregnant women; the legislative paradox whereby sanctions may be imposed on women in certain professional categories who refuse vaccination because they are pregnant; and the possible legal consequences in the event of harm to the unborn child due to vaccination. All of this is considered in accordance with the principles of medical ethics, taking into account the national legislation

    The “magnificent seven errors” in forensic autopsy practice”: the Italian Context

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    Medical examiners (MEs) have a very complex set of responsibilities centered on the performance of a forensic autopsy. The quality of this activity is always questioned in the courts of incorrect evaluations are dangerous because they can jeopardize the validity of a criminal investigation and thus affect the outcome, so that a real culprit can be acquitted or an innocent person convicted. Non-compliance also discredits the professionalism of the specialist performing the autopsy. The work of a forensic scientist implies a series of assignments and tasks that should be taken into constant consideration, but when some aspects of this activity are underestimated or neglected, this can lead the expert to commit errors with irreparable consequences for the judicial investigation. In this paper we take an in-depth look at seven potential errors related to autopsy activity following death from unnatural causes, with the aim of providing practical guidelines for SMEs. These relate to: oversights in autopsy technique; erroneous collection of photographic and video material; unauthorized participation in the autopsy; reporting failures/misses at any stage of the forensic activity; failure to notify the consulting forensic party; using unaccredited histology or toxicology laboratories for forensic activities; and failure to follow the chain of custody
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