Organ procurement in forensic deaths: A retrospective analysis of the Italian context with a focus on the Puglia Region virtuous experience.

Organ transplantation is one the most important contributions of modern medicine to society since it provides a unique therapy for terminal organ failure. However, the development of this therapeutic approach is hindered by the limited organ supply. In Italy, organ procurement requires a multidisciplinary medical-surgical approach in which legal medical doctors (LMDs) are generally tasked with ascertaining the reality of death. Sometimes, a medico-legal report is required when the deceased's family deny their consent to the organs and tissues removal from a potential deceased donor. LMDs can also be appointed by law to carry out post-mortem examinations of potential deceased donors. In these cases, the public prosecutors' interest in preserving the corpse integrity for forensic purposes seems to conflict with the ethical-humanitarian interest in promoting, at most, the opportunity to donate; however, a LMD can act as a mediator and allow both goals. This paper aims to illustrate the Apulia Region experience in reconciling the justice interests with those of a culture promoting deceased organ and tissue donation. It has been pursued by analyzing the virtuous regional organ procurement trend in forensic deaths before and after a crucial 2015 initiative, comparing the results with the national ones, and contextualizing them in the relevant literature to show systemic strengths and weaknesses and inform future Italian policy development.

Validation and application of a method for the quantification of 137 drugs of abuse and new psychoactive substances in hair.

INTRODUCTION: In the dynamic universe of new psychoactive substances (NPS), the identification of multiple and chemically diverse compounds remains a challenge for forensic laboratories. Since hair analysis represents a gold-standard to assess the prevalence of NPS, which are commonly detected together with classical drugs of abuse (DoA), our study aimed at developing a wide-screen method to detect and quantify 127 NPS and 15 DoA on hair. MATERIALS AND METHODS: A multi-analyte ultra-high performance liquid chromatography mass spectrometry method for the identification and quantification of 127 NPS (phenethylamines, arylcyclohexylamines, synthetic opioids, tryptamines, synthetic cannabinoids, synthetic cathinones, designer benzodiazepines) and 15 DoA in hair samples was developed. A full validation was performed according to the European medicines Agency (EMA) guidelines, by assessing selectivity, linearity, accuracy, precision, limit of quantification (LOQ), limit of detection (LOD), matrix effect and recovery. As a proof of the applicability, the method was applied to 22 authentic hair samples collected for forensic purposes. RESULTS: Successful validation was achieved, by meeting the required technical parameters, for 137 compounds (122 NPS and 15 DoA), with LOQ set at 4 pg/mg for 129 compounds, at 10 pg/mg for 6 and at 40 pg/mg for 2. The method was not considered validated for 5 NPS, as LLOQ resulted too high for a forensic analysis (80 pg/mg). Among authentic forensic samples, 17 tested positive for DoA, and 10 to NPS, most samples showing positivity for both. Detected NPS were ketamine and norketamine, 5-MMPA, ritalinic acid, methoxyacetyl fentanyl, methylone and RCS-4. CONCLUSION: The present methodology represents an easy, low cost, wide-panel method for the quantification of 122 NPS and 15 DoA, for a total of 137 analytes, in hair samples. The method can be profitably applied by forensic laboratories. Similar multi-analyte methods on the hair matrix might be useful in the future to study the prevalence of NPS and the co-occurrence of NPS-DoA abuse.

Immune disturbance leads to pulmonary embolism in COVID-19 more than classical risk factors: a clinical and histological study.

COVID-19 induces endotheliitis and one of the main complications is enhanced coagulation. The incidence of pulmonary embolism (PE) in COVID-19 (CPE) has increased and clinical features for a rigorous analysis still need to be determined. Thus, we evaluated the clinical characteristics in CPE and the immune infiltration that occurred. Between January 1 and December 31, 2021, 38 patients were affected by CPE (9 ICU, 19 males/19 females, 70.18 ± 11.24 years) out of 459 COVID-19 cases. Controls were subjects who were evaluated for PE between January 1 2015, and December 31, 2019 (92 patients, 9 ICU, 48 males/45 females, 69.55 ± 16.59 years). All patients underwent complete physical examination, pulmonary computed tomography, laboratory tests, D-dimer, and blood gas analysis. There were no differences in laboratory tests or D-dimer. In patients with CPE, pO2, alveolar-arterial oxygen difference (A-aDO2), oxygen saturation %, and the ratio between arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2), P/F, were significantly increased. There were no differences in PaCO2. Platelet count was inversely correlated to P/F (r = - 0.389, p = 0.02) but directly to A-aDO2 (r = 0.699, p = 0.001) only in patients with CPE. Histology of lung biopsies (7 CPE/7 controls) of patients with CPE showed an increase in CD15+ cells, HMGB1, and extracellular MPO as a marker of NETosis, while no significant differences were found in CD3+, CD4+, CD8+, and intracellular MPO. Overall, data suggest that CPE has a different clinical setting. Reduced oxygen content and saturation described in Patients with CPE should not be considered a trustworthy sign of disease. Increased A-aDO2 may indicate that CPE involves the smallest vessels as compared to classical PE. The significant difference in NETosis may suggest the mechanism related to thrombi formation.

Work-related stress amongst legal medical doctors: the need for systematic psychological support. An Italian perspective.

Legal medical doctors (LMDs) expertise encompasses a wide range of responsibilities. Work-related stress amongst LMDs is an extremely relevant factor, which affects the quality of LMDs life and work. Whilst it is a better-known problem abroad, this issue is poorly debated in Italy, as demonstrated by this literature analysis. The aim of this paper is to better understand the main sources of stress in the practice of legal medicine in Italy, highlighting the need for systematic psychological support. The risks of work-related stress for the social and health professions are well known in literature. In Italy, however, due to a series of complex circumstances and cultural and research delays, forensic practitioners often seem to be excluded from these kinds of complex issues. The authors, after a series of considerations drawn from a review of the literature and from experience in the forensic and medical field, point out how work in this area entails risks for workers, on par with all others belonging to the helping and social-health professions. They conclude their contribution with a series of proposals for appropriate protocols to cope with such problems for workers in the forensic and medical field. Key points: Work-related risks for the social and health professionals are widely recognized in the literature.Although legal medical doctors are often thought to be safe from these types of issues, significant risks exist for this category as well.It is important to create appropriate protocols to address outcomes for legal medical doctors.

Denial of pregnancy and neonaticide: A historical overview and case report.

While denial of pregnancy and neonaticide are rare, they are potentially associated and share some risk factors. Neonaticide has been proposed as the extreme outcome of a denial of pregnancy. However, the process leading to such a possible outcome is not yet fully understood. The primary goal of this essay is to examine the various definitions and ambiguities surrounding the denial of pregnancy. The case of a young woman with a history of two denied pregnancies with diverse characteristics and outcomes, the latest of which resulted in neonaticide, is then reported and examined. A forensic psychiatric evaluation was also performed to reconstruct the woman's mental state at the time of the crime. The forensic pathological analysis of the newborn, abandoned near the sea while still alive, is described. The victim's body showed signs of shaken baby syndrome. We contend that differing levels of awareness during a denial of pregnancy might not be predictive of the potential delivery outcome in terms of threat to the newborn's survival, according to the forensic pathological and psychopathological data of the current case. Early identification of women affected by denial of pregnancy who pose a danger of committing infanticide is hampered by both intrinsic traits (dissimulation, unawareness, low propensity to seek assistance) and environmental factors (isolation, low socioeconomic level, poor education.). A previous history of denial of pregnancy should activate health and support services to reduce the potential risks for the mother and the child.

"Freedom and Dignity Are Worth More than Life": The Dramatic Suicide of an Anti-Vax Man.

Since the beginning of the COVID-19 public health emergency, we have witnessed an increase in psychiatric problems and pathologies, such as depression, anxiety, isolation, posttraumatic stress disorder, substance abuse, and burnout. The world's collective sentiment finally turned toward optimism after authorization was granted for the COVID-19 vaccines' emergency use by the FDA in December 2020. With the increase in vaccine coverage in Western countries, case counts and deaths gradually plummeted while activity restrictions were progressively lifted. At the same time, however, a new COVID-19-related public health issue has arisen, as a substantial number of eligible individuals refused vaccination. Behaviors assumed by the so-called anti-vax people in manifesting their own opposition towards COVID-19 vaccination are various, and sometimes assume the forms of dramatic gestures with symbolic value, such as suicide. Here, we present the case of a healthy, convinced anti-vax, 58-year-old man, who allowed himself to be run over by a moving train in the presence of eyewitnesses, bringing with him a demonstrative note of his reasons. The present article aims to raise awareness against the social and psychological impact of COVID-19 vaccination refusal and to point out the need of a specific support net to avoid the spread of psychological impairment, social isolation and suicidal behaviors among the "anti-vax community".

A fatal case of heart and pericardium rupture after non-penetrating chest trauma by road accident.

Heart lacerations following a non-penetrating chest trauma are rare events, few described in the literature. We report the case of a young woman who died just after a road accident, which determined a blunt thoracic trauma, with perforation of the right ventricle and the contiguous pericardium portion, and compound fractures of the sternum and the left ribs. The case presented is a rare evidence of indirect heart trauma, meaning that there was no correspondence between the chest impact/fracture site and the heart/pericardial lacerations.

Loa loa in the Vitreous Cavity of the Eye: A Case Report and State of Art.

Loa loa is a filarial nematode responsible for loiasis, endemic to West-Central Africa south of the Sahara and transmitted by flies. This study reports a case of L. loa in the vitreous cavity of the eye of a young patient, along with an in-depth literature review. A 22-year-old woman from Cameroon who migrated from Cameroon to Italy was referred to the Emergency Ophthalmology Department at Policlinico di Bari in July 2021 with the presence of a moving parasite in the subconjunctiva of the left eye. A recent onset of a papular lesion on the dorsal surface of the right wrist and a nodular lesion in the scapular region were detected. L. loa filariasis was diagnosed based on anamnestic data, clinical and paraclinical signs, and a parasitological test confirming the presence of microfilariae in two blood samples collected in the morning of two different days. Because of the unavailability of diethylcarbamazine (DEC), albendazole (ALB) 200 mg twice daily was administered for 21 days. A mild exacerbation of pruritus occurred during treatment, but resolved with the use of an antihistamine. A single dose of 12 mg ivermectin was prescribed at the end of the treatment with albendazole. Unlike other endemic parasite infections, L. loa is not included in the Global Program to Eliminate Lymphatic Filariasis, because it is not mentioned in the WHO and CDC list of neglected tropical diseases. This can result in an overall risk of lack of attention and studies on loiasis, with lack of data on global burden of the disease.

SARS-CoV-2, Placental Histopathology, Gravity of Infection and Immunopathology: Is There an Association?

(1) Background: As the pandemic months progress, more and more evidence shows that the placenta acts as a "barrier" to SARS-CoV-2, although rare cases of vertical transmission have been described. (2) Methods: In an attempt to investigate whether the symptoms' severity was related to different placental histological characteristics and the immune microenvironment, we subdivided 29 placentas from 29 mothers positive for SARS-CoV-2 into two groups, depending on the symptomatology (moderate/severe vs. asymptomatic/mild), performing immunohistochemical investigations for CD4 + and CD8 + T lymphocytes, as well as for CD68 + macrophage. We also evaluated the immuno-expression of the ACE2 receptor at the placental level. These two groups were compared to a control group of 28 placentas from 28 SARS-CoV-2-negative healthy mothers. (3) Results: The symptoms (likely to be related to viremia) were statistically significantly correlated (p < 0.05) with histopathological changes, such as maternal malperfusion, decidual arteriopathy, blood vessel thrombus of fetal relevance. Furthermore, the immuno-expression of ACE2 was significantly lower in SARS-CoV-2-positive groups vs. control group (p = 0.001). (4) Conclusions: There is still much to study and discover regarding the relationship between SARS-CoV-2 and histological changes in placentas and how the latter might contribute to various neonatal clinical outcomes, such as prematurity.

A Patient With Stage III Locally Advanced Pancreatic Adenocarcinoma Treated With Intra-Arterial Infusion FOLFIRINOX: Impressive Tumoral Response and Death due to Legionella pneumophila Infection: A Unique Case Report.

Patients affected by pancreatic ductal adenocarcinoma (PDAC) have very poor prognosis, whereby at a follow-up of 5 years, the mortality rate is very similar to the incidence rate. Globally, around 10% of patients are amenable to radical surgery at the time of diagnosis, which represents the only chance of cure or long-term survival for these patients. Almost 40% of patients with PDAC show locally advanced pancreatic cancer (LAPC). LAPC is not a metastatic disease, although it is not amenable to radical surgery. For these patients, systemic induction chemotherapy with intravenous FOLFIRINOX (5-fluorouracil, folic acid, irinotecan, oxaliplatin) regimen is administered, with the aim of conversion to surgery, although the conversion rate remains low, at approximately 10% to 15%. Pancreatic arterial chemotherapy has been explored to overcome the intrinsic tumor pancreatic resistance to systemic chemotherapy, where an intra-arterial port-a-cath is placed by means of interventional oncology techniques under angiographic guidance in the operating theater. Here, we treated a patient with an intra-arterially modified FOLFIRINOX regimen. Three courses were administered, and the patient experienced no adverse events. At the end of the third course, the patient rapidly developed lung failure due to nosocomial Legionella pneumophila infection, despite the impressive pathological tumor response shown in the autopsy report. This is a first and unique report that demonstrates that pancreatic intra-arterial FOLFIRINOX can be safe and efficacious. We believe that this preliminary result will be confirmed in the next patients to be enrolled and that it provides a glimmer of hope for patients with this lethal disease.

An Unusual Case of Fatal Thoracoabdominal Gunshot Wound without Diaphragm Injury.

In case of thoracoabdominal gunshot wounds (GSW), diaphragmatic lesions are common autopsy findings. In these cases, the bullet's path involves both the thorax and the abdomen, so the diaphragm (the muscle that separates the two cavities) is frequently damaged. In the present report we illustrate a very unusual autopsy finding, came up after a man was shot twice and affected by a lethal thoracoabdominal gunshot wound. In particular, as expected based on CT scans, the corpse exhibited a thoracic-abdominal path and a retained bullet in the abdomen, but no diaphragmatic lesions or hemorrhagic infiltrations of this muscle have been detected during the autopsy. After a scrupulous examination and the section of all the organs, the intracorporeal projectile's path was reconstructed, inferring that the thoracoabdominal transit of the bullet extraordinarily had occurred in correspondence of the diaphragmatic inferior vena cava's ostium, thus exploiting a natural passage without damaging the diaphragmatic muscle.

Dental evidence of human remains of a Slavic soldier population deported in concentration camps during World War II.

Aims: The aim of this paper was to analyse post-mortem dental records of a collection of 93 skeletal remains exhumed from the ossuary of Bari Municipal Cemetery, Apulia, Italy. These skeletal remains belonged to Slavic soldiers deported in 1941 during World War II in two Italian concentration camps and who died in 1946-1947. Methods: A total number of 1949 teeth were analysed according to the American Board of Forensic Odontology and the WHO methods. The majority of the victims were men (95%) between the age of 18 and 62. Results: The results showed the dental health situation of a population of soldiers of World War II, in particular the high rate of caries (35%), periodontal disease (61%), and dental wear (65%) according to the high stress level of the soldiers during the armed conflict and the subsequent deportation. Conclusions: This is the first study reported in literature that analyses the effects of war and deportation on soldiers' pathological conditions of the oral cavity. This analysis also confirmed the usefulness of teeth for anthropological and forensic research thanks to their high resistance and preservation even after post-mortem modifications and different environmental factors.

Necrotizing Fasciitis of the Thigh as Unusual Colonoscopic Polypectomy Complication: Review of the Literature with Case Presentation.

Necrotizing fasciitis (NF) is an infection characterized by necrosis of the superficial muscle fascia and surrounding soft tissues. It usually occurs following skin breaches from penetrating traumas or high-degree burns. Less frequently, it could be related to major abdominal surgery. However, no cases of thigh NF after minor abdominal procedures have ever been reported. A previously healthy 59-year-old male patient underwent a colonoscopic polypectomy. After the procedure, the patient developed an increasing right groin pain. The CT scan showed a gas collection in the right retroperitoneum space and in the right thigh soft tissues. Thus, a right colon perforation was hypothesized, and the patient was moved to the nearest surgery department and underwent a right hemicolectomy procedure. During surgery, the right thigh was also incised and drained, with gas and pus leakage. Nevertheless, the right lower limb continued to swell, and signs of systemic infection appeared. Afterward, clinical conditions continued to worsen despite the drainage of the thigh and antibiotic therapy, and the patient died of septic shock after just two days. This case shows that, although rare, lower limb NF should be considered among the causes of early post-operative local painful symptoms.

Torkildsen's Ventriculocisternostomy First Applications: The Anthropological Evidence of a Young Slavic Soldier Who Died in the Torre Tresca Concentration Camp (Bari, Italy) in 1946.

Human skeletal remains are considered as real biological archives of each subject's life. Generally, traumas, wounds, surgical interventions, and many human pathologies suffered in life leave identifiable marks on the skeleton, and their correct interpretation is possible only through a meticulous anthropological investigation of skeletal remains. The study here presented concerns the analysis of a young Slavic soldier's skeleton who died, after his imprisonment, in the concentration camp of Torre Tresca (Bari, Italy), during the Second World War (1946). In particular, the skull exhibited signs of surgical activity on the posterior cranial fossa and the parieto-occipital bones. They could be attributed to surgical procedures performed at different times, showing various degrees of bone edge remodeling. Overall, it was possible to correlate the surgical outcomes highlighted on the skull to the Torkildsen's ventriculocisternostomy (VCS), the first clinically successful shunt for cerebrospinal fluid (CSF) diversion in hydrocephalus, which gained widespread use in the 1940s. For this reason, the skeleton we examined represents a rare, precious, and historical testimony of an emerging and revolutionary neurosurgical technique, which differed from other operations for treating hydrocephalus before the Second World War and was internationally recognized as an efficient procedure before the introduction of extracranial shunts.

GLUT1, GLUT3 Expression and 18FDG-PET/CT in Human Malignant Melanoma: What Relationship Exists? New Insights and Perspectives.

BACKGROUND: Malignant melanoma is the most aggressive of skin cancers and the 19th most common cancer worldwide, with an estimated age-standardized incidence rate of 2.8-3.1 per 100,000; although there have been clear advances in therapeutic treatment, the prognosis of MM patients with Breslow thickness greater than 1 mm is still quite poor today. The study of how melanoma cells manage to survive and proliferate by consuming glucose has been partially addressed in the literature, but some rather interesting results are starting to be present. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a search of PubMed and Web of Sciences (WoS) databases was performed until 27 September 2021 using the terms: glucose transporter 1 and 3 and GLUT1/3 in combination with each of the following: melanoma, neoplasm and immunohistochemistry. RESULTS: In total, 46 records were initially identified in the literature search, of which six were duplicates. After screening for eligibility and inclusion criteria, 16 publications were ultimately included. CONCLUSIONS: the results discussed regarding the role and expression of GLUT are still far from definitive, but further steps toward understanding and stopping this mechanism have, at least in part, been taken. New studies and new discoveries should lead to further clarification of some aspects since the various mechanisms of glucose uptake by neoplastic cells are not limited to the transporters of the GLUT family alone.

Dedifferentiated Melanoma: A Diagnostic Histological Pitfall-Review of the Literature with Case Presentation.

Dedifferentiated melanoma is a particular form of malignant melanoma with a progressive worsening of the patient's clinical outcome. It is well known that melanoma can assume different histo-morphological patterns, to which specific genetic signatures correspond, sometimes but not always. In this review we address the diagnostic difficulties in correctly recognizing this entity, discuss the major differential diagnoses of interest to the dermatopathologist, and conduct a review of the literature with particular attention and emphasis on the latest molecular discoveries regarding the dedifferentiation/undifferentiation mechanism and more advanced therapeutic approaches.

Purpuric Skin Rash in a Patient Undergoing Pfizer-BioNTech COVID-19 Vaccination: Histological Evaluation and Perspectives.

The COVID-19 pandemic has affected the entire planet, and within about a year and a half, has led to 174,502,686 confirmed cases of COVID-19 worldwide, with 3,770,361 deaths. Although it is now clear that SARS-CoV-2 can affect various different organs, including the lungs, brain, skin, vessels, placenta and others, less is yet known about adverse reactions from vaccines, although more and more reports are starting to emerge. Among the adverse events, we focused particularly on skin rashes. In this short report, we describe the case of a patient vaccinated with Comirnaty, who developed a purpuric rash resistant to oral steroid therapy after 2 weeks. To date, this is one of the very few cases in which skin biopsy was performed to better characterize the histopathological picture of this rash. Finally, we conduct a literature review of the cases of rashes from SARS-CoV-2 vaccines described in the literature, with the aim of laying foundations for future, larger case studies.

HMGB1-TIM3-HO1: A New Pathway of Inflammation in Skin of SARS-CoV-2 Patients? A Retrospective Pilot Study.

The SARS-CoV-2 pandemic has completely disrupted the health systems of the entire planet. From the earliest months, it became increasingly clear that in addition to affecting the upper airways and lungs, there were other organs that could be affected. Among these, the skin became a real "sentinel signal" to be able to even suspect COVID-19. Background: this study deals with a little-explored issue for now: the study of skin immunopathology in SARS-CoV-2 positive subjects ascertained using the most reliable methods available. Methods: we used skin biopsy samples from SARS-CoV-2 positive and negative patients, studying morphology (Hematoxylin-Eosin), T lymphocyte population (CD4 and CD8), three markers such as HMGB-1, TIM-3 and HO-1 by immunohistochemistry. Results: although the presence of the CD4 and CD8 T population did not differ statistically significantly, we found greater activation and release of HMGB-1 in skin samples from SARS-CoV-2 positive patients, greater immunolabeling for TIM-3 at the level of CD4 and CD8 and a reduced expression of Heme oxygenase 1. Conclusions: these results support the possibility that there is immune deregulation in SARS-CoV-2 positive patients who develop skin manifestations of various kinds.

SARS-CoV-2 and Skin: The Pathologist's Point of View.

The SARS-CoV-2 pandemic has dramatically changed our lives and habits. In just a few months, the most advanced and efficient health systems in the world have been overwhelmed by an infectious disease that has caused 3.26 million deaths and more than 156 million cases worldwide. Although the lung is the most frequently affected organ, the skin has also resulted in being a target body district, so much so as to suggest it may be a real "sentinel" of COVID-19 disease. Here we present 17 cases of skin manifestations studied and analyzed in recent months in our Department; immunohistochemical investigations were carried out on samples for the S1 spike-protein of SARS-CoV-2, as well as electron microscopy investigations showing evidence of virions within the constituent cells of the eccrine sweat glands and the endothelium of small blood vessels. Finally, we conduct a brief review of the COVID-related skin manifestations, confirmed by immunohistochemistry and/or electron microscopy, described in the literature.