A Survey on Undergraduate Medical Students' Perception of COVID-19 Vaccination.

The objectives of this study were to obtain information on medical students' attitudes toward COVID-19 vaccination and to identify the main barriers to its acceptance. We conducted an anonymous online survey on a sample of undergraduate medical students from one main Italian University. The questions were aimed at exploring their attitudes toward vaccination to prevent COVID-19, their perceptions of the risk/threat of COVID-19 and the factors associated with their attitudes toward COVID-19 vaccination. A high percentage of students in our sample stated that they had been vaccinated or that they intended to be vaccinated against the COVID-19 coronavirus. A total of 239 questionnaires were analyzed. Age, social, geographic and demographic characteristics, health conditions and interest in vaccination were recorded; 93% of the students declared that they encouraged vaccination and 83% stated that the reason was "Moral responsibility towards the community". Four students had not yet been vaccinated, mainly because of "Contradictory information on efficacy and safety". The Likert-type questions revealed high agreement on the importance of vaccination and whether it should be made mandatory ("indispensable tool" and "ethical duty" were cited to explain this position). The results show a high level of acceptance of COVID-19 vaccination among these medical undergraduates who, being halfway through their training and involved in clinical practice, are already in possession of specific scientific knowledge and, to a small extent, come from different areas of Italy.

Myeloma Spine and Bone Damage Score (MSBDS) on Whole-Body Computed Tomography (WBCT): Multiple Reader Agreement in a Multicenter Reliability Study.

Objective: To assess the reliability of the myeloma spine and bone damage score (MSBDS) across multiple readers with different levels of expertise and from different institutions. Methods: A reliability exercise, including 104 data sets of static images and complete CT examinations of patients affected by multiple myeloma (MM), was performed. A complementary imaging atlas provided detailed examples of the MSBDS scores, including low-risk and high-risk lesions. A total of 15 readers testing the MSBDS were evaluated. ICC estimates and their 95% confidence intervals were calculated based on mean rating (k = 15), absolute agreement, a two-way random-effects model and Cronbach's alpha. Results: Overall, the ICC correlation coefficient was 0.87 (95% confidence interval: 0.79-0.92), and the Cronbach's alpha was 0.93 (95% confidence interval: 0.94-0.97). Global inter- and intra-observer agreement among the 15 readers with scores below or equal to 6 points and scores above 6 points were 0.81 (95% C.I.: 0.72-0.86) and 0.94 (95% C.I.:0.91-0.98), respectively. Conclusion: We present a consensus-based semiquantitative scoring systems for CT in MM with a complementary CT imaging atlas including detailed examples of relevant scoring techniques. We found substantial agreement among readers with different levels of experience, thereby supporting the role of the MSBDS for possible large-scale applications. Significance and Innovations • Based on previous work and definitions of the MSBDS, we present real-life reliability data for quantitative bone damage assessment in multiple myeloma (MM) patients on CT. • In this study, reliability for the MSBDS, which was tested on 15 readers with different levels of expertise and from different institutions, was shown to be moderate to excellent. • The complementary CT imaging atlas is expected to enhance unified interpretations of the MSBDS between different professionals dealing with MM patients in their routine clinical practice.

A Rare Case of Fatal Thyroid Hemorrhage After Fine-Needle Aspiration: Case Report and Review of the Literature.

ABSTRACT: Sudden death due to massive hemorrhage after a mini-invasive ambulatory diagnostic procedure is extremely rare. Fine-needle aspiration (FNA) of thyroid nodules is very safe, displaying a low rate of complications, all of which mild and often self-limiting. In few cases do these complications necessitate surgical decompression, and rarely does FNA of a thyroid nodule lead to the death of the patient.We report a case of sudden death caused by respiratory insufficiency after compression of the vascular and nervous structures of the neck and obstruction of the upper airways by hemorrhages dissecting the thyroidal and perithyroidal tissues in a 78-year-old woman. These hemorrhages were the result of vascular lacerations caused during diagnostic FNA of a nodule suspected of malignancy. In such cases, it is important to conduct a complete autopsy and histological analysis to ascertain the origin of massive hemorrhage involving the structures of the neck and to attribute the cause of death to the aforementioned procedure. The forensic pathologist must bear in mind that even extremely small damage, such as that produced by a fine needle, may cause a fatal hemorrhage in subjects with a subverted anatomo-pathological picture (such as, for example, the massive fibrosis of an organ).

Otorrhagia in strangulations: An important but often underestimated finding in forensic pathology.

In forensic practice, it is not always easy to determine whether a person has died from strangulation. The recommended physical examination includes a thorough inspection of the head, neck, oral cavity, and eyes. Ligature marks are sometimes absent or poorly delineated, especially when soft devices are used. Otorrhagia is poorly described in neck compression, and it is often an underestimated finding. Here, we report a case of massive bilateral otorrhagia produced during strangulation (death by garrotting), and we discuss the possible pathophysiological mechanisms. As our case demonstrates, otorrhagia can be a sign of neck compression and can aid in the diagnosis of death from strangulation. Therefore, a thorough examination of the external ear and otoscopy are recommended procedures in cases concerning for strangulation.

Case Report: A Peculiar Case of Inflammatory Colitis After SARS-CoV-2 Infection.

We report a case of inflammatory colitis after SARS-CoV-2 infection in a patient with no additional co-morbidity who died within three weeks of hospitalization. As it is becoming increasingly clear that SARS-CoV-2 infection can cause immunological alterations, we investigated the expression of the inhibitory checkpoint PD-1 and its ligand PD-L1 to explore the potential role of this axis in the break of self-tolerance. The presence of the SARS-CoV-2 virus in colon tissue was demonstrated by qRT-PCR and immunohistochemical localization of the nucleocapsid protein. Expression of lymphocyte markers, PD-1, and PD-L1 in colon tissue was investigated by IHC. SARS-CoV-2-immunoreactive cells were detected both in the ulcerated and non-ulcerated mucosal areas. Compared to healthy tissue, where PD-1 is weakly expressed and PD-L1 is absent, PD-1 and PD-L1 expression appears in the inflamed mucosal tissue, as expected, but was mainly confined to non-ulcerative areas. At the same time, these markers were virtually undetectable in areas of mucosal ulceration. Our data show an alteration of the PD-1/PD-L1 axis and suggest a link between SARS-CoV-2 infection and an aberrant autoinflammatory response due to concomitant breakdown of the PD-1/PD-L1 interaction leading to early death of the patient.

Ante-mortem characterization of sudden deaths as first-manifestation in Italy.

PURPOSE: There is a relative paucity of data on ante-mortem clinical characteristics of young (age 1 to 35 years) sudden death (SD) victims. The aim of the study was to characterize ante-mortem characteristics of SD victims, in a selected national cohort identified by a web search. METHODS: A dataset of all SD (January 2010 and December 2015) was built from national forensic data and medical records, integrated with Google search model. Families were contacted to obtain consent for interviews. Data were obtained on ante-mortem symptoms. ECG characteristics and autopsy data were available. RESULTS: Out of 301 SD cases collected, medical and family history was available in 132 (43.9%). Twenty-eight (21.1%) had a positive family history for SD. SD occurred during sport/effort in 76 (57.6%). One hundred twelve (85%) SD cases had no prior reported symptoms. Autopsy data were available in 100/132 (75.8%) cases: an extra cardiac cause was identified in 20 (20%). Among the 61 cases with a cardiac diagnosis, 21 (34%) had hypertrophic cardiomyopathy. Among the 19 (19%) victims without structural abnormalities, molecular autopsy identified pathogenic variants for channelopathies in 9 cases. Ten (10%) victims had no identifiable cause. CONCLUSIONS: Most SD were due to cardiac causes and occurred in previously asymptomatic patients. SD events mainly occurred during strenuous activity. In a minority of cases, no cause was identified. The web-based selection criteria, and incomplete data retrieval, need to be carefully taken into account for data interpretation and reproducibility.

CT-derived relationship between low relative muscle mass and bone damage in patients with multiple myeloma undergoing stem cells transplantation.

OBJECTIVE: Sarcopenia or low muscle mass is related to worse prognosis in cancer patients. We investigated whether muscle mass is related to bone damage on CT in patients with multiple myeloma (MM). METHODS: Approval from the institutional review board was obtained. N = 74 consecutive patients (mean age, 60.8 years ± 9.24 [standard deviation]; range, 36-89 years) for MM who underwent transplant were included. Sarcopenia cut-off points defined as skeletal muscle index (SMI) used were<41 cm2/m2. To assess bone damage in MM the MSBDS (myeloma spine and bone damage score) was used. One-way analysis of variance and the X2 test were used. Kaplan-Meier analysis was performed to generate progression and survival curves according to SMI and MSBDS. The testing level was set at 0.05. RESULTS: The median SMI was 47.1 ± 14.2 and according to SMI 18/74 (24%) had sarcopenia which was more prevalent in females (p.001). A strong and significant association between patients with low muscle mass and elevated bone damage (24/74, 32.4%) and patients with normal/non-low muscle mass low bone damage (30/74, 40.5%) was present. Multiple Logistic regression did not show any significant relationship or confounding influence among SMI and MSBDS regarding sex (p.127), cytogenetic status (p.457), staging (p.756) and relapse (.126). Neither SMI nor MSBDS resulted significantly related to overall survival as shown in Kaplan-Meier analysis. CONCLUSION: Sarcopenia and bone damage affected MM patients undergoing stem cell transplantation and are significantly associated. ADVANCES IN KNOWLEDGE: Quantitative measurement of sarcopenia and bone damage on CT resulted present in MM patients undergoing stem cell transplantation and are significantly associated.

Early Administration of Bamlanivimab in Combination with Etesevimab Increases the Benefits of COVID-19 Treatment: Real-World Experience from the Liguria Region.

Monoclonal antibodies, such as bamlanivimab and etesevimab combination (BEC), have been proposed for patients with mild or moderate coronavirus disease 2019 (COVID-19). However, few studies have assessed the factors associated with the early administration of BEC or the impact of early BEC treatment on the clinical evolution of the patients. We conducted a retrospective cohort study of all adults with COVID-19 who received BEC at three institutions in the Liguria region. The primary endpoint was to investigate the clinical variables associated with early BEC infusion. Secondary endpoints were 30-day overall mortality and the composite endpoint of requirement of hospital admission or need for supplemental oxygen during the 30-day follow-up period. A total of 127 patients (median age 70 years; 56.7% males) received BEC. Of those, 93 (73.2%) received BEC within 5 days from symptoms onset (early BEC). Patients with a higher Charlson comorbidity index were more likely to receive early treatment (odds ratio (OR) 1.60, 95% confidence interval (CI) 1.04-2.45; p = 0.03) in contrast to those reporting fever at presentation (OR 0.26, 0.08-0.82; p = 0.02). Early BEC was associated with lower likelihood of hospital admission or need for supplemental oxygen (OR 0.19, 0.06-0.65; p = 0.008). Five patients who received early BEC died during the follow-up period, but only one of them due to COVID-19-related causes. Early bamlanivimab and etesevimab combination was more frequently administered to patients with a high Charlson comorbidity index. Despite this, early BEC was associated with a lower rate of hospital admission or need for any supplementary oxygen compared to late administration. These results suggest that efforts should focus on encouraging early BEC use in patients with mild-moderate COVID-19 at risk for complications.

Development and Validation of a Questionnaire investigating the Knowledge, Attitudes and Practices of Healthcare Workers in the Field of Anesthesiology concerning the Italian Law on Advance Healthcare Directives: a Pilot Study.

Advance healthcare directives are legal documents, in which the patient, foreseeing a potential loss of capacity and autonomy, makes in advance decisions regarding future care and, in particular, end-of-life arrangements. In Italy, advance healthcare directives  are regulated by the Law 219 of 22 December 2017. Objectives of the study were: i) to develop and validate a questionnaire dedicated to evaluate the knowledge of the Law in a sample of 98 anesthesiologists, and ii) to shed light on the process of health-related decision-making and its determinants (age, gender, doctor/training resident, religious beliefs). A second part of the survey  not analyzed  in the present study, aimed to assess, through two simulated clinical scenarios, how patient' directives, relatives and the medical staff could influence physicians' clinical decision. Overall Cronbach's alpha coefficient of the questionnaire resulted 0.83. Three factors explaining up to 38.4% of total variance (communication and relationship with the patient; critical life-threatening situations and binding nature of the advance directive for the physician; and involvement of patients). Most of the doctors (58.7%) did not fully know the recent legislative provision. The lack of knowledge is critical in view of the specificity of the clinical area investigated (anesthesiology and intensive care), which has to cope with ethical issues. An adequate revision and implementation of the traditional curricula could help medical students and trainees develop the aptitudes and skills needed in their future profession.

COVID-19 Pandemic and Equal Access to Vaccines.

The COVID-19 pandemic has evidenced the chronic inequality that exists between populations and communities as regards global healthcare. Vaccination, an appropriate tool for the prevention of infection, should be guaranteed by means of proportionate interventions to defeat such inequality in populations and communities affected by a higher risk of infection. Equitable criteria of justice should be identified and applied with respect to access to vaccination and to the order in which it should be administered. This article analyzes, as regards the worldwide distribution of anti-COVID-19 vaccines, the various ways the principle of equity has been construed and applied or even overlooked. The main obstacle to equal access to vaccines is vaccine nationalism. The perception of equity varies with the differing reference values adopted. Adequate response to needs appears to be the principal rule for achieving the criterion of equity in line with distributive justice. Priorities must be set equitably based on rational parameters in accordance with current needs. The entire process must be governed by transparency, from parameter identification to implementation. The issue of equal access to vaccination affects the entire world population, necessitating specific protective interventions. In light of this, the World Health Organization (WHO) has devised the COVAX plan to ensure that even the poorest nations of the world receive the vaccine; certain initiatives are also supported by the European Union (EU). This pandemic has brought to the fore the need to build a culture of equitable relationships both in each country's own domain and with the rest of the world.

Immunohistochemistry in postmortem diagnosis of acute cerebral hypoxia and ischemia: A systematic review.

BACKGROUND: : Discovery of evidence of acute brain ischemia or hypoxia and its differentiation from agonal hypoxia represents a task of interest but extremely difficult in forensic neuropathology. Generally, more than 50% of forensic autopsies indicate evidence of brain induced functional arrest of the organ system, which can be the result of a hypoxic/ischemic brain event. Even if the brain is the target organ of hypoxic/ischemic damage, at present, there are no specific neuropathological (macroscopic and histological) findings of hypoxic damage (such as in drowning, hanging, intoxication with carbon monoxide) or acute ischemia. In fact, the first histological signs appear after at least 4 to 6 hours. Numerous authors have pointed out how an immunohistochemical analysis could help diagnose acute cerebral hypoxia/ischemia.Data sources: This review was based on articles published in PubMed and Scopus databases in the past 25 years, with the following keywords "immunohistochemical markers," "acute cerebral ischemia," "ischemic or hypoxic brain damage," and "acute cerebral hypoxia". OBJECTIVES: : Original articles and reviews on this topic were selected. The purpose of this review is to analyze and summarize the markers studied so far and to consider the limits of immunohistochemistry that exist to date in this specific field of forensic pathology. RESULTS: : We identified 13 markers that had been examined (in previous studies) for this purpose. In our opinion, it is difficult to identify reliable and confirmed biomarkers from multiple studies in order to support a postmortem diagnosis of acute cerebral hypoxia/ischemia. Microtubule-associated protein 2 (MAP2) is the most researched marker in the literature and the results obtained have proven to be quite useful. CONCLUSION: Immunohistochemistry has provided interesting and promising results, but further studies are needed in order to confirm and apply them in standard forensic practice.

The Difficult Balance between Ensuring the Right of Nursing Home Residents to Communication and Their Safety.

The COVID-19 epidemic has had a profound impact on healthcare systems worldwide. The number of infections in nursing homes for the elderly particularly is significantly high, with a high mortality rate as a result. In order to contain infection risks for both residents and employees of such facilities, the Italian government passed emergency legislation during the initial stages of the pandemic to restrict outside visitor access. On 30 November 2020, the Italian President of the Council of Ministers issued a new decree recognizing the social and emotional value of visits to patients from family and friends. In addition, it indicated prevention measures for the purposes of containing the infection risk within nursing homes for the elderly. This article comments on these new legislative provisions from the medicolegal perspective, providing indications that can be used in clinical practice.

Taking care of life: the new Italian law on post-mortem donation for study purposes, training and scientific research.

Anatomical dissection is considered a fundamental practice in the medical curriculum. Not only does it help students to familiarize themselves with the various bodily organs and to refine their surgical practice, it also fosters an attitude of awareness and respect towards death and the values of solidarity. On 10th February 2020, the Italian Parliament passed a new law entitled "Rules on the disposition of one's own body and post-mortem tissues for study purposes, training and scientific research". Here, we outline the main ethical and legal aspects of this law and suggest initiatives to encourage body donation. Through careful analysis of the law, we intend to open a discussion on the main ethical issues and to make comparisons with the international situation. The new legislation fills serious gaps in an area of great ethical relevance; not only does it endorse fundamental ethical principles, it also provides important guidelines for strengthening body donation, such as: ensuring respect for the dignity of the deceased, providing express consent, appointing a trustee, promoting information for both doctors and the community, and banning all forms of trade in bodies or body parts. This law is certainly an important milestone on the road to overcoming the scarcity of bodies for study and research. However, it is also essential to promote a favourable attitude to body donation and to strive to overcome obstacles to this practice by supporting continuous dialogue between anatomical institutes and the community. Further studies are necessary in order to assess the impact of the new law.

Forensic pathological study of methadone-related deaths in the Genoa (Italy) district: A six-year study.

Methadone is a synthetic opioid, a pure agonist of the µ receptor. It is used for opioid maintenance therapy in heroin addiction. In recent years, Italian studies of incidence and prevalence have indicated an increase in the illegal sales of methadone and, consequently, an increase in deaths due to acute methadone intoxication as well. The present review is a prospective-observational study regarding epidemiological and toxicological analyses of methadone-related deaths recorded in the district of Genoa (Italy) from 2013 to 2018. The study includes a list of twenty-six people that have died from methadone toxicity: twenty-two males and four females. The concentration of methadone in the blood samples ranged from 181 to 4058.53 ng/mL, with an average of 964.29 ng/mL. Six subjects tested positive for methadone alone; twenty cases, however, presented drugs or substances in different concentrations in the blood samples. Illegal sales and consumption of methadone have a negative impact on the self-administration therapy of opioid addiction, inducing patients to increase their dosage or sell methadone in order to purchase illegal drugs. As shown in our study, this behaviour is associated with an increase in methadone-related deaths. Accordingly, careful monitoring of dosage administrated to patients is required in order to render the system safer.

Philemon and Baucis deaths: A case of two siblings and state of the art.

The simultaneous discovery of two corpses at the same scene obliges the forensic pathologist to consider many circumstances. First, the hypothesis of homicide/crime has to be investigated. However, when the circumstances, autopsy, histological data and toxicological and biochemical analyses suggest a natural cause of death, Philemon and Baucis syndrome should be considered. While a few cases of Philemon and Baucis deaths involving couples of spouses have been reported in the literature, only one paper describes the simultaneous deaths of two siblings. The case presented here concerns the death of two siblings who were found in an advanced stage of decomposition in their apartment, which had been allocated to them by social services. The victims were known to be living in conditions of social and economic deprivation and to be suffering from psychiatric disorders. The first suspected cause of death was malnutrition. However, this was excluded by complete autopsy, histological studies and, especially, biochemical investigations, which excluded starvation ketoacidosis. Moreover, no evidence of trauma or poisoning was found in either of the bodies. Despite the advanced stage of decomposition, one of the bodies presented with histological signs of myocardial sclerosis, left ventricular hypertrophy and contraction band necrosis, suggesting that the mechanism of death involved a fatal arrhythmia. The circumstances and the post-mortem findings were highly suggestive of Philemon and Baucis syndrome.

Fatal hemorrhage from a periumbilical wound: Stabbing or hemorrhage from a caput medusae?

Varices are the main clinical manifestation of portal hypertension, and their bleeding is the predominant cause of mortality from this condition. Periumbilical varices are known as "caput medusae." Reports of their bleeding are rare, with only three fatal cases described in the literature. The antemortem diagnosis is relatively simple, while the postmortem diagnosis is more complex. This paper is the first report of fatal hemorrhage from a caput medusae for which the diagnosis was made postmortem, thanks to a complete diagnostic process including scene and circumstances, medical history, and autopsy with detailed histology. The circumstantial analysis showed the presence of a large amount of blood at the scene, blood which originated from a small abdominal wound; an analysis of the subject's clinical data reported that he was affected by portal hypertension. The autopsy revealed some dilated and convoluted veins in the subcutaneous tissue of the umbilical region; a fistula between these veins and the abdominal wound was detected. The histological study confirmed the presence of periumbilical varices, one of them ruptured and connected with the overlying skin. The cause of death was attributed to a massive hemorrhage generated by a periumbilical varix in a patient affected by portal hypertension.

Sudden and unexpected death in childhood due to an undiagnosed hepatoblastoma: Case report and review of literature.

The sudden and unexpected death of an infant or child due to cancer is a particularly rare event. Most of the cases concern primary growths located in vital organs such as the heart or the brain. Only in an extremely small number of cases does it occur in infants or children affected by liver cancer. Herein we report the sudden and unexpected death of a 3-and-a-half-year-old infant, who due to an undiagnosed tumor of the liver, namely hepatoblastoma, suffered a major intra-abdominal (hemoperitoneum) bleed, leading to a fatal hemorrhagic trauma. In cases like these, it is of utmost importance to carry out both an autopsy as well as complete histological tests in order to determine if the hepatic tumor is the real cause of death or if it was a mere chance finding. In the case of sudden and unexplained deaths in infancy and childhood, the forensic pathologist should always consider that other complications, for example, those correlated with hepatoblastoma could, in fact, cause sudden death given that this particular tumor is often scarcely symptomatic and can remain undiscovered for a long period of time.

The Motion of the Italian National Bioethics Committee on Aggressive Treatment towards Children with Limited Life Expectancy.

The motion of the Italian National Bioethics Committee entitled "Aggressive treatment or therapeutic obstinacy on young children with limited life expectancy" comprises a premise that rejects therapeutic obstinacy and makes 12 recommendations. Recommendation no. 1 states the general rules: it ascribes a cardinal role to a shared care plan, it supports pain management therapy and pain relief, it opposes ineffective and disproportionate clinical treatment and defensive medicine. The other recommendations are correlated to the enacting of a national law establishing clinical ethics committees in paediatric hospitals; participation of parents and their fiduciaries in the decision-making processes; recourse to courts only as extrema ratio in the event of irremediable disagreement between the medical team and the family members; accompaniment at the end of life also through continuous deep sedation combined with pain therapy; access to palliative care; the need to reinforce research on pain and suffering in children; clinical trials and research studies conducted in children; the training of doctors, healthcare personnel and psychologists, to support parents in emotional and practical terms; the facilitation of the closeness of parents to children in extremely precarious clinical conditions; the relevant role of the associations of parents of sick children. Comments are made, in particular, about the innovative recommendations respectively relating to the adoption of care planning, the establishment, by law, of clinical ethics committees in paediatric hospitals and the limitation of recourse to courts-only as extrema ratio-in the event of irremediable disagreement between the medical team and the family members.