Syncope and Cannabis: hypervagotonia from chronic abuse? A case report and literature review.

BACKGROUND: Cannabis is the most consumed drug worldwide and number of users is increasing, particularly among youth. Moreover, cannabis potential therapeutic properties have renewed interest to make it available as a treatment for a variety of conditions. Albeit rarely, cannabis consumption has been associated with cardiovascular diseases such as arrhythmias, myocardial infarction (MI) and potentially sudden death. CASE PRESENTATION: A 24-year-old woman presented to the emergency department sent by her cardiologist because of a recent finding of a 16 seconds asystole on the implantable loop recorder (ILR) she implanted 7 months before for recurrent syncopes. She declared that she is a heavy cannabis user (at least 5 cannabis-cigarette per day, not mixed up with tobacco, for no less than 12 years) and all syncopes occurred shortly after cannabis consumption. After a collective discussion with the heart team, syncope unit, electrophysiologists and toxicologist, we decided to implant a dual chamber pacemaker with a rate response algorithm due to the high risk of trauma of the syncopal episodes. 24 months follow-up period was uneventful. CONCLUSIONS: Cannabis cardiovascular effects are not well known and, although rare, among these we find ischemic episodes, tachyarrhythmias, symptomatic sinus bradycardia, sinus arrest, ventricular asystole and possibly death. Because of cannabis growing consumption both for medical and recreational purpose, cardiovascular diseases associated with cannabis use may become more and more frequent. In the light of the poor literature, we believe that cannabis may produce opposite adverse effects depending on the duration of the habit. Acute administration increases sympathetic tone and reduces parasympathetic tone; conversely, with chronic intake an opposite effect is observed: repetitive dosing decreases sympathetic activity and increases parasympathetic activity. Clinicians should be aware of the increased risk of cardiovascular complications associated with cannabis use and should investigate its consumption especially in young patients presenting with cardiac dysrhythmias.

The potential of micro-CT for dating post-cranial bone fractures: a macroscopic, radiographic, and microtomography study of fractures of known post-traumatic ages.

The estimation of the post-traumatic survival time (PTST) in case of bone injuries remains a tricky issue in the forensic field, especially when dealing with dry bones. Newer high-resolution imaging, and in particular microcomputed tomography (micro-CT), has the potential to significantly improve our abilities to interpret antemortem and perimortem lesions and accurately date fractures in a less destructive analysis. In this paper, nine costal fractures of known post-traumatic ages were analyzed through gross examination, conventional radiography, and microcomputed tomography, in order to test the potential of microcomputed tomography for dating fractures. As a result, microcomputed tomography provided images of high quality and definition and allowed the observation of the internal microarchitecture of the fractures and calluses. While microcomputed tomography cannot substitute histological examination for the estimation of the post-traumatic survival time, it constitutes a potent and helpful complementary tool for the analysis of bone trauma.

Homicide and concealment of the corpse. Autopsy case series and review of the literature.

INTRODUCTION: The concealment of the body following a homicide undermines different moments of the forensic and medico-legal investigations. The aim of the present study is to provide an overview of the literature and the forensic casuistry of the Institute of Legal Medicine of Padova for analyzing and discussing diverse methodological approaches for the forensic pathologist dealing with covered-up homicides. MATERIAL AND METHODS: A literature review, updated until September 2019, was performed, and a literature pool of forensic cases was built. In-house cases were included by conducting a retrospective analysis of the forensic caseworks of Padova of the last 20 years. Data regarding epidemiology, methodology of assessment, methods of concealment, and answers to medico-legal issues were extracted for both data sets. RESULTS AND DISCUSSION: Seventy-eight papers were included in the literature review (78.2% being case reports or case series, 17% retrospective studies, and 6% experimental studies or reviews). Literature and in-house data sets consisted of 145 and 13 cases, respectively. Death scene investigation, radiology, toxicology, and additional analyses were performed in 20-54% of literature and 62-77% of in-house cases. Cover-up by multiple methods prevailed. Death was caused by head trauma in about 40% of cases (both data sets), strangulation in 21% of literature, and 7% of in-house cases, and was undetermined in 17% of literature and 7% of in-house cases. CONCLUSIONS: The methodology of ascertainment should be case-specific and based on a multidisciplinary and multimodal evaluation of all data, including those gained through novel radiological and/or analytical techniques.

Intra-class and inter-class tool discrimination through micro-CT analysis of false starts on bone.

Micro-CT has successfully been applied to the characterization of false starts (FSs) and, among several parameters, kerf width seems to correlate to the tool blade. The aim of the present study was to evaluate the diagnostic value of micro-CT for the differentiation of saw marks produced by different classes of saws and by saws belonging to the same class and differing only in number of teeth per inches (TPI). A morphological and morphometric analysis of 84 marks, produced by 6 saws belonging to 3 morphological classes, was performed. In the experimental cohort, for each parameter, statistically significant differences in intra- and inter-class analysis were searched for and cut-offs were established. The diagnostic accuracy of cut-offs was assessed through statistical analyses on the validation cohort. The morphological assessment did not allow to differentiate saws differing only in TPI. Angle 1 and top kerf width, respectively for cross-cut and rip-cut saws with alternating set, allowed a good discrimination between FSs produced by tools belonging to the same morphological class. High positive predictive values were found in intra-class analyses, while results in inter-class analyses were less encouraging. In cases of dismemberment, a micro-CT-based analysis of FSs is strongly suggested as a part of a multistep and multimodal methodology of assessment, which includes scanning electron microscopy and stereomicroscopy. A morphological assessment should be followed by an experimental trial and by a morphometric analysis. Further studies are needed to evaluate hampering factors, such as damage by physico-chemical agents.

Radiological investigation of gunshot wounds: a systematic review of published evidence.

INTRODUCTION: Despite the constantly growing popularity of radiological imaging in forensic pathology, a systematic review investigating the efficiency and limits of radiological techniques, in comparison to forensic autopsy, was still missing. AIM: The present review aims at providing an overview on the current role of radiology in the forensic investigation of fatal gunshot wounds without any restriction to specific radiological techniques. MATERIAL AND METHODS: A systematic literature search on three databases (PubMed, Web of Science, and Science Direct) was performed until December 2017. The Oxford Centre for Evidence Based Medicine (OCEBM) grading system for levels of evidence was applied, in order to weigh published evidence. RESULTS AND DISCUSSION: Eighty-six papers (1.64% of the records) were included. Despite the quite limited general level of evidence, which contrasts with the abundance of the scientific literature on this topic, several recommendations/statements, coupled to their OCEBM grade, were distilled as for the identification of retained bullets, gunshot wounds detection, diagnosis of entrance and exit wounds, trajectories and internal injury detection and estimation of the firing distance. CONCLUSIONS: Imaging radiological technologies represent the present and future of wound ballistics. However, traditional, micro and molecular imaging techniques require further validation through blinded cross-sectional studies with appropriate reference standards (e.g. forensic autopsy).

Post-mortem thermal angiography: a pilot study on swine coronary circulation.

Thermal imaging (TI) allows the detection of thermal patterns emitted from objects as a function of their temperature in the long-infrared spectrum and produces visible images displaying temperature differences. The aim of this pilot study was to test TI to visualize the coronary circulation of swine hearts. Thirty swine hearts were prepared for ex situ coronarography, and thermal images were acquired through a FlirOne thermal camera (FLIR Systems®) paired with a Google Android Smartphone. Coronary arteries were cannulated, namely the anterior interventricular artery, the circumflex branch of the left coronary artery, and the right coronary artery. The heart was cooled, and contrast medium (CM) consisting of distilled water heated to 40 °C was injected in a coronary vessel, while thermal images were captured. These steps were repeated for each coronary vessel and under experimentally simulated coronary heart disease. Thermal imaging coronarography (TIC) allowed a clear representation of the morphology and course of the coronary vessels and of experimentally simulated coronary heart disease, moreover, demonstrated to be easy to perform during or after autopsies on ex situ hearts, non-destructive, reproducible, and cheap. On the basis of these preliminary results, TIC might allow a subsequent more focused and comprehensive cardiopathological examination of the heart, which remains mandatory for the definitive diagnosis of coronary heart disease. Although these preliminary results seem encouraging, further systematic studies on human hearts, both normal and pathological, are necessary for estimating the sensitivity and specificity of the proposed method and to draw any definitive conclusion.

Skin lesions and traditional folk practices: a medico-legal perspective.

The correct assessment of signs of abuse on the skin is a challenge of utmost importance for both clinical and forensic applications. This review aims to investigate how differing cultural behaviors influence the perception of abuse, focusing on the need for a multidisciplinary approach and investigation. A literature search for articles that discussed folk practices from a forensic perspective was performed; articles with reference to abuse in the description of the main folk healing techniques and with reference to the differential diagnosis between physical abuse and skin injuries due to folk healing techniques were selected. A synoptic table of all skin injuries produced by folk healing techniques, divided by geographical area, was created. This table can be used as a tool for the thorough assessment of typical signs detectable on the skin, thus aiding in a differential diagnosis. The first approach to the patient represents a crucial step toward the identification of abuse; forensic practitioners ought to be aware of the existence of folk healing techniques which may mimic signs that can be interpreted as physical abuse in children and adults.

Necrotizing fasciitis: case series and review of the literature on clinical and medico-legal diagnostic challenges.

Necrotizing fasciitis (NF) is a life-threatening infection of soft tissues spreading along the fasciae to the surrounding musculature, subcutaneous fat and overlying skin areas that can rapidly lead to septic shock and death. Due to the pandemic increase of medical malpractice lawsuits, above all in Western countries, the forensic pathologist is frequently asked to investigate post-mortem cases of NF in order to determine the cause of death and to identify any related negligence and/or medical error. Herein, we review the medical literature dealing with cases of NF in a post-mortem setting, present a case series of seven NF fatalities and discuss the main ante-mortem and post-mortem diagnostic challenges of both clinical and forensic interests. In particular, we address the following issues: (1) origin of soft tissue infections, (2) micro-organisms involved, (3) time of progression of the infection to NF, (4) clinical and histological staging of NF and (5) pros and cons of clinical and laboratory scores, specific forensic issues related to the reconstruction of the ideal medical conduct and the evaluation of the causal value/link of any eventual medical error.

The Dangerous Pattern of Concurrent Use of Alcohol and Cocaine Among Drunk-Drivers of Northeast Italy.

AIM: To estimate the prevalence of drug and polydrug use among drunk-drivers during the driving license regranting program, in order to assess the inclusion of toxicological tests on hair and urine samples in the systematic methodology in this category of subjects. SHORT SUMMARY: A total of 2160 drunk-drivers were tested for alcohol and drugs during driving license regranting. Thirty-one subjects showed alcohol use, 212 illicit drug use and, among these, 131 were polydrug users. Nineteen different patterns of drug and polydrug use were found. Cocaine was detected in 165 subjects. METHODS: The study was performed on 2160 drunk-drivers examined at Legal Medicine and Toxicology Unit of the University of Padova, in a 3-year-period (2014-2017). The positivity for one or more illicit drugs in hair or urine samples was confirmed by LC/MS and GC/MS methods. Chi-square test, Fischer's exact test and Cochran-Armitage Trend test were used to study the correlation between general characteristics of the examined sample and the presence of drug/polydrug use. RESULTS: Thirty-one subjects showed alcohol use, 212 illicit drug use and, among these, 131 were polydrug users. Nineteen different patterns of drug and polydrug use were found. Cocaine was detected in 165 subjects in whom 122 showed a concurrent use of alcohol and cocaine, identified through the detection of cocaethylene in hair samples. No significant association and/or trends between drug/polydrug use and the general characteristics of the sample were detected. CONCLUSIONS: The results show that drug and polydrug use among drunk-drivers should be subjected to toxicological as well as alcohological monitoring, especially in the regranting procedure. The implementation of this procedure could improve the knowledge of dimensions of the issue, providing a powerful means for the reduction of phenomenon of driving under the influence of alcohol and drugs.

Back to the Future - Part 1. The medico-legal autopsy from ancient civilization to the post-genomic era.

Part 1 of the review "Back to the Future" examines the historical evolution of the medico-legal autopsy and microscopy techniques, from Ancient Civilization to the Post-Genomic Era. In the section focusing on "The Past", the study of historical sources concerning the origins and development of the medico-legal autopsy, from the Bronze Age until the Middle Ages, shows how, as early as 2000 BC, the performance of autopsies for medico-legal purposes was a known and widespread practice in some ancient civilizations in Egypt, the Far East and later in Europe. In the section focusing on "The Present", the improvement of autopsy techniques by Friedrich Albert Zenker and Rudolf Virchow and the contemporary development of optical microscopy techniques for forensic purposes during the 19th and 20th centuries are reported, emphasizing, the regulation of medico-legal autopsies in diverse nations around the world and the publication of international guidelines or best practices elaborated by International Scientific Societies. Finally, in "The Future" section, innovative robotized and advanced microscopy systems and techniques, including their possible use in the bio-medicolegal field, are reported, which should lead to the improvement and standardization of the autopsy methodology, thereby achieving a more precise identification of natural and traumatic pathologies.

Back to the Future - Part 2. Post-mortem assessment and evolutionary role of the bio-medicolegal sciences.

Part 2 of the review "Back to the Future" is dedicated to the evolutionary role of the bio-medicolegal sciences, reporting the historical profiles, the state of the art, and prospects for future development of the main related techniques and methods of the ancillary disciplines that have risen to the role of "autonomous" sciences, namely, Genetics and Genomics, Toxicology, Radiology, and Imaging, involved in historic synergy in the "post-mortem assessment," together with the mother discipline Legal Medicine, by way of its primary fundament, universally denominated as Forensic Pathology. The evolution of the scientific research and the increased accuracy of the various disciplines will be oriented towards the elaboration of an "algorithm," able to weigh the value of "evidence" placed at the disposal of the "justice system" as real truth and proof.

Micro-CT features of intermediate gunshot wounds covered by textiles.

The analysis of gunshot residue (GSR) on the clothing and the underlying skin of the victim may play an important role in the reconstruction of the shooting incident. The aim of the present study was to test micro-computed tomography (micro-CT) for the analysis of firearm wounds experimentally produced on human skin covered by textiles. Firing trials were performed on 60 sections of human calves enveloped by a single layer of fabric (cotton or jeans or leather or nylon) and 15 controls consisting of bare calves. Experimental firings were conducted in a ballistic laboratory at three different muzzle-to-target distances (5, 15, and 30 cm), using a .32 ACP pistol (Beretta Mod. 81) loaded with full-jacketed bullets coming from the same production lot (7.65 × 17 mm, Browning SR). The visual inspection revealed the classic pattern of GSR distribution on the fabrics and the skin of control samples, while only a dark ring around the entrance lesion was identified on the skin beneath the fabrics. Micro-CT analysis showed the presence of radiopaque material on all entrance wounds, with a statistically significant difference between cases and controls. No differences were found among specimens covered by fabrics, with regard to the firing distance and the type of clothing. No GSR-like deposits were detected in exit wounds. Our results suggest that micro-CT analysis may be a useful screening tool for differentiating entry from exit gunshot wounds when the covering textiles are contaminated, damaged, or missing.

Padova Charter on personal injury and damage under civil-tort law : Medico-legal guidelines on methods of ascertainment and criteria of evaluation.

Compensation for personal damage, defined as any pecuniary or non-pecuniary loss causally related to a personal injury under civil-tort law, is strictly based on the local jurisdiction and therefore varies significantly across the world. This manuscript presents the first "International Guidelines on Medico-Legal Methods of Ascertainment and Criteria of Evaluation of Personal Injury and Damage under Civil-Tort Law". This consensus document, which includes a step-by-step illustrated explanation of flow charts articulated in eight sequential steps and a comprehensive description of the ascertainment methodology and the criteria of evaluation, has been developed by an International Working Group composed of juridical and medico-legal experts and adopted as Guidelines by the International Academy of Legal Medicine (IALM).

Morphometric analysis of stab wounds by MSCT and MRI after the instillation of contrast medium.

OBJECTIVE: To analyze the morphology and depth of stab wounds experimentally produced on human legs amputated for medical reasons using multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) after the instillation of a single contrast medium solution (CMS). MATERIALS AND METHODS: For morphological analysis, MSCT and MRI scans were performed before and after the instillation of CMS into the wound cavity. Depth measurements were performed on the sagittal view only after CMS instillation. Subsequently, each wound was dissected using the layer-by-layer technique and the depth was measured by a ruler. One-way between-groups pairwise analysis of variance (ANOVA) and Bland-Altman plot analysis were used for comparing radiological and anatomical measurements. RESULTS: Unenhanced MSCT images did not identify the wound channels, whereas unenhanced MRI evidenced the wound cavity in 50 % of cases. After the instillation of CMS, both MSCT and MRI depicted the wound channel in all the investigated stabbings, although the morphology of the cavity was irregular and did not resemble the shape of the blade. The radiological measurements of the wounds' depth, after the application of CMS, exhibited a high level of agreement (about 95 % at Bland-Altman plot analysis) with the anatomical measurements at dissection. A similar systematic underestimation, however, has been evidenced for MSCT (average 11.4 %; 95 % CI 7-17) and MRI (average 9.6 %; 95 % CI 6-13) data after the instillation of CMS with respect to wound dissection measurements. CONCLUSION: MSCT and MRI after the instillation of CMS can be used for depicting the morphometric features of stab wounds, although depth measurements are affected by a slight systematic underestimation compared to layer-by-layer dissection.

Can immunohistochemistry quantification of Cathepsin-D be useful in the differential diagnosis between vital and post-mortem wounds in humans?

Markers of skin wound vitality and the research methodology used for their determination are still matters of debate in forensic pathology. Cathepsin-D, a lysosomal enzyme, is the most expressed cathepsin in human skin, and although it seems to have the necessary requirements to be utilized as a vitality marker, past research has provided no definitive and clear response on its potential usefulness. Immunohistochemistry with monoclonal antibodies and image analysis has been employed to detect and quantify the expression of Cathepsin-D in human skin wounds. We analyzed skin fragments obtained from 20 living individuals (group A) and 20 persons deceased from natural causes (group B). For each case, five skin fragments were withdrawn at 0', 5', 10', 30', and 90' after abdominal incision. Once the samples were formalin-fixed and paraffin-embedded, we analyzed the expression of Cathepsin-D through the quantification of the immunohistochemistry signal by image analysis. Immunoreactivity was displayed in Pixels of positive area measured by image analysis and converted in micrometer squares. The average levels of Cathepsin-D were higher in group B than in group A, except in three cases which showed a lower expression, with a statistically significant difference of Cathepsin-D expression between the two groups (p < 0.0001). Group B showed unvaried levels among the progressive samples and group A revealed an increasing predominant trend at 30'. Due to the high levels of expression of Cathepsin-D found in the post-mortem injuries, our study definitively excludes any usefulness of immunohistochemistry quantification of this enzyme in the differentiation between vital and post-mortem injuries.

Medically assisted suicide in Italy: Recent legal developments on a controversial topic.

On 16th June 2022, the first case of lawful 'medically assisted suicide' took place on Italian soil. This event is a result of decade-long debates on informed consent and end-of-life care stimulated by medical jurisprudence. The authors first retrace the crucial moments that allowed this to happen and underline the problems still to be solved. The cases of DJ Fabo, Davide Trentin, Mario and Fabio Ridolfi are discussed, signalling how they influenced the path implemented by Italian jurisprudence.

Ethyl glucuronide concentration in hair for detecting heavy drinking and/or abstinence: a meta-analysis.

In both clinical and forensic settings, hair analysis for ethyl glucuronide (HEtG) has been increasingly employed for diagnosing chronic excessive drinking and, more recently, for monitoring abstinence. This paper aims at meta-analysing published data on HEtG concentrations in teetotallers, social drinkers and heavy drinkers in order to evaluate the use of this marker in hair for identifying chronic excessive drinking and for monitoring abstinence. In May 2012, a systematic multi-database search retrieved 366 records related to HEtG and further screened for relevant publications in the field. Fifteen (4.1 %) records matched the selection criteria and were included in the meta-analysis. The mean and 95 % confidence intervals (CI) of HEtG concentrations in social drinkers (mean 7.5 pg/mg; 95 % CI 4.7-10.2 pg/mg; p < 0.001), heavy drinkers (mean 142.7 pg/mg; 95 % CI 99.9-185.5 pg/mg; p < 0.001) and deceased subjects with a known history of chronic excessive drinking (mean 586.1 pg/mg; 95 % CI 177.2-995.0 pg/mg; p < 0.01) were calculated. The ranges of mean values and 95 % confidence intervals for single studies involving teetotallers/social or social/heavy drinkers showed a partial overlap with a down-trespassing of both the 7 and 30 pg/mg thresholds for social and heavy drinkers, respectively. Although larger and well-designed population studies are required to draw any definitive conclusion, our data show that the cut-off of 30 pg/mg limits the false-negative effect in differentiating heavy from social drinkers, whereas the recently proposed 7 pg/mg cut-off value might only be used for suspecting an active alcohol use, and not for proving complete abstinence.

Monitoring haloperidol exposure in body fluids and hair of children by liquid chromatography-high-resolution mass spectrometry.

BACKGROUND: Haloperidol, 4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]-1-(4-fluorophenyl)-1-butanone (HP), one of the most widely used antipsychotics in the treatment of schizophrenia, mania, and other psychiatric disorders, is frequently encountered in cases of unintentional pediatric intoxication because the ingestion of a small amount can cause significant toxic effects in children. For monitoring HP in suspected ingestions, a liquid chromatography-high-resolution mass spectrometry method has been developed and validated in urine, blood, and hair samples. METHODS: The analyte was extracted from 1 mL blood or urine by liquid/liquid extraction and from 5 mg of hair by micropulverized extraction; gradient elution on an Atlantis T3 column was realized using HP-d4 as an internal standard. Positive ion electrospray ionization and high-resolution mass spectrometry determination were performed in an Orbitrap mass spectrometer. RESULTS: The method exhibited a r > 0.999 in the studied ranges (0.1-50 ng/mL in urine and blood and 0.1-50 ng/mg in hair) and a limit of quantification of 0.1 ng/mL for urine and blood and 0.1 ng/mg for hair; intra-assay and interassay relative SDs were always more than 18%. The method was applied to determine haloperidol in 3 children who were admitted to emergency departments. HP concentrations ranged from 2 to 21 ng/mL in urine, from not detected to 4.9 ng/mL in blood, and from 0.37 to 0.73 ng/mg in hair samples. CONCLUSIONS: The utilization of high-resolution/high-accuracy mass spectrometry in full scan mode allowed the identification of HP metabolites in urine and blood, thus unequivocally documenting the exposure to the drug. HP metabolites were structurally characterized by high-resolution multiple mass spectrometry. For the first time, a HP metabolite was detected in hair.

MicroCT detection of gunshot residue in fresh and decomposed firearm wounds.

Gunshot residue (GSR) evidence may be altered or obscured by after-death events such as putrefaction, autolysis, and/or damage by animals. The present study aimed at evaluating and comparing the amount and differential distribution of GSR utilizing microcomputed tomography (microCT) analysis of fresh and decomposed gunshot wounds. A total of 60 experimental shootings at three different firing distances (5, 15, and 30 cm) were performed on human calves surgically amputated for medical reasons. Thirty specimens (10 for each tested distance) were immediately formalin-fixed, while the other 30 specimens were enclosed in a cowshed for 15 days, before formalin fixation (air temperature ranging from 11°C to 38°C). MicroCT analysis with three-dimensional image reconstruction detected GSR particles in all the investigated entrance wounds. In fresh specimens, GSR was concentrated on the skin surface around the entrance hole and in the epidermis and dermis layers around the cavity, while in decomposed specimens, the high density particles were detected only in the dermis layer. No GSR was detected in exit wounds of both fresh and decomposed specimens regardless of the tested firing distance. Statistical analysis demonstrated that also in decomposed wounds the amount of GSR roughly correlated with the distance from which the gun was fired, exhibiting, however, a higher variability than in fresh samples. The obtained results suggest that microCT analysis can be a valid screening tool for differentiating decomposed entrance and exit gunshot wounds.