Retrospective analysis of anaesthesia-related deaths during a 12-year period: looking at the data from a forensic point of view.

Anaesthesia-related death is one of the most complex events to be studied in forensic pathology because of its rarity and its doubtful presentation. Particularly, the difficulties in assessing the cause of deaths in such circumstances are underlined. A scale must be considered in order to determine the causal role of anaesthesia in the process leading to death. Indeed, beyond deaths exclusively explained by anaesthetic care, there are deaths that are not anaesthesia-related and deaths explained by surgery and co-morbidities in which the role of anaesthetic care has to be carefully investigated. A retrospective analysis of 3138 autopsies is presented with the aim of better understanding the patho-physiological process of anaesthesia-related mortality and to determine the causal role of anaesthesiological care in the process leading to death, thus assessing the real incidence of deaths due to anaesthesia (0.16%). In the present study, the number of deaths generically anaesthesia-related (33 cases) accounts for 2.06% of autopsies due to medical malpractice claims and 1.05% of all autopsies. The number of deaths totally related to anaesthesic care is rather low with 0.32% of autopsies due to medical malpractice claims and 0.16% of all autopsies. Anaesthesia-related deaths were due to lack of or delay in intubation (2 cases), acute cardio-respiratory failure (2 cases) and anaesthetic-induced hepatotoxicity (1 case). The importance of a careful forensic investigation (clinical and familial history, medical records, complete autopsy and toxicology), which can lead to a clear understanding of anaesthesia-related deaths, is also stressed.

Acute administration of 3,4-methylenedioxymethamphetamine (MDMA) induces oxidative stress, lipoperoxidation and TNFα-mediated apoptosis in rat liver.

Liver toxicity is one of the consequences of ecstasy (3,4-methylenedioxymethamphetamine MDMA) abuse and hepatocellular damage is reported after MDMA consumption. Various factors probably play a role in ecstasy-induced hepatotoxicity, namely its metabolism, the increased efflux of neurotransmitters, the oxidation of biogenic amines, and hyperthermia. MDMA undergoes extensive hepatic metabolism that involves the production of reactive metabolites which form adducts with intracellular nucleophilic sites. MDMA-induced-TNF-α can promote multiple mechanisms to initiate apoptosis in hepatocytes, activation of pro-apoptotic (BID, SMAC/DIABLO) and inhibition of anti-apoptotic (NF-κB, Bcl-2) proteins. The aim of the present study was to obtain evidence for the oxidative stress mechanism and apoptosis involved in ecstasy-induced hepatotoxicity in rat liver after a single 20 mg/kg, i.p. MDMA administration. Reduced and oxidized glutathione (GSH and GSSG), ascorbic acid (AA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA), an indicator of lipid peroxidation, were determined in rat liver after 3 and 6h after MDMA treatment. The effect of a single MDMA treatment included decrease of GR and GPx activities (29% and 25%, respectively) and GSH/GSSG ratio (32%) with an increase of MDA (119%) after 3h from ecstasy administration compared to control rats. Liver cytosolic level of AA was increased (32%) after 6 h MDMA treatment. Our results demonstrate a strong positive reaction for TNFα (p<0.001) in hepatocytes and a diffuse apoptotic process in the liver specimens (p<0.001). There was correlation between immunohistochemical results and Western blotting which were quantitatively measured by densitometry, confirming the strong positivity for TNF-α (p<0.001) and NF-κB (p<0.001); weak and intense positivity reactions was confirmed for Bcl-2, SMAC/DIABLO (p<0.001) and BID reactions (p<0.001). The results obtained in the present study suggest that MDMA induces loss of GSH homeostasis, decreases antioxidant enzyme activities, and lipoperoxidation that causes an oxidative stress that accompaines the MDMA-induced apoptosis in liver cells.

Lethal injuries following building collapse: comparison between autopsy and radiographic findings.

PURPOSE: The aim of this study was to evaluate the impact of conventional radiology on the assessment of causes of death of human beings after a building collapse and to establish whether the radiographic approach is useful and justifiable. MATERIALS AND METHODS: Eight victims of a building collapse were subjected to autopsy, toxicology and radiographic examinations of the entire body. The autopsy findings, classified into three groups according to the New Injury Severity Score (NISS), were compared with radiographic findings. RESULTS: The death of the three individuals in group 1 was ascribed to mechanical asphyxia. Costal fractures, pneumothorax and subcutaneous emphysema were detected in one case only. The three individuals in group 2 died of mechanical asphyxia associated with cerebral injuries in all cases, abdominal injuries in two and cardiac injuries in one. Plain films showed skull fracture in one case, air within the cardiac chambers in another and diaphragmatic injuries in the third. The two individuals in group 3 died of injuries not compatible with life at the cardiac and abdominal level in both cases and at the cerebral level in one. Radiography showed multiple fractures of the cranium associated with diaphragmatic injuries in one case only. No significant pleuropulmonary radiographic findings were detected in any of the eight victims. Paralytic ileus, identified in all patients, is not strictly correlated to abdominal injuries. Skeletal injuries were all confirmed at conventional radiography. CONCLUSIONS: Conventional radiography allows for the overall assessment of skeletal injuries. Radiographic findings provide limited information about the causes of death, whereas findings related to the concomitant causes of death are more frequent. Conventional radiography should be considered inadequate, especially if the potential of the modern software tools available on current computed tomography and magnetic resonance images is considered.

Crossbow injuries: A case report with experimental reconstruction study and a systematic review of literature.

In modern times crossbow - a ranged weapon diffused during Middle Ages - is increasing its popularity in recreational hunting and sports; crossbow bolts have a great penetration capacity, despite their low initial velocity. Great concerns emerge when considering that notwithstanding crossbow is a potentially lethal distance weapon, it is easy to obtain without having to undertake any tests on the buyer's mental or physical health. Although rare, crossbow injuries can be challenging for the forensic pathologist due to great similarities with other wounds pattern (gunshots wounds or injury due to sharp force). Especially when the arrow is removed from its original position or the body is decomposed, identification of the weapon can be difficult. According to forensic literature, suicides, homicides and non-lethal injuries by crossbow have been reported up to the present day. We followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) indications in the identification and selection of studies and reviewed a series of cases of both fatal and non-fatal crossbow injuries, according to the manner of death (homicide, suicide, accidental). The casuistic part of this paper deals with an attempted murder of a 21-year old man: a case of non-lethal crossbow injury of the thorax in which an interdisciplinary approach, involving forensic inspection, ballistic and radiology tests, led to solve the case.

C3a, TNF-alpha and interleukin myocardial expression in a case of fatal sudden cardiac failure during clinic reactivation of systemic lupus erythematosus.

Isolated myocarditis, or dilated cardiomyopathy, is a rare and usually late clinical manifestation of systemic lupus erythematosus (SLE). Increased levels of complement split products are associated with disease activity. Injury of the vascular endothelium due to complement activation and immune complexes may contribute to the vasculopathy in SLE. We present a case of sudden cardiac failure and death in a 28-year-old Caucasian man, during reactivation of SLE. To explain the sudden cardiac failure, we looked for anti-tumour necrosis factor (TNF)- proportional, variant and anti-interleukin (IL) expression in cardiac cells, and anti-complement (anti-C)3a in small cardiac vessels. The immunohistochemical examination of heart specimens revealed a strong positive reaction in cardiac myocytes for antibodies anti-TNF- proportional, variant and IL-8, and a milder positive reaction for antibodies anti-IL-15 and IL-10. A strong positive reaction of C3a in small cardiac vessels was observed in all specimens. Furthermore, the expression of CD4 and CD8 showed a strong positive reaction in pericardium and valvular endocardium, and a lesser positivity in myocardial specimens. TNF appears to have played a major proinflammatory role in this fatal case.

Virtopsy versus digital autopsy: virtual autopsy.

Multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) are being increasingly implemented in forensic pathology. These methods may serve as an adjuvant to classic forensic autopsies. Imaging of the interior of corpses is performed using MSCT and/or MRI. MRI, in addition, is also well suited to the examination of surviving victims of assault, especially choking, and helps visualise internal injuries sometimes not seen on external examination of the victim. Various postprocessing techniques can provide strong forensic evidence for use in legal proceedings. The documentation and analysis of postmortem findings with MSCT and MRI and postprocessing techniques (virtopsy) is investigator independent, objective and noninvasive and will lead to qualitative improvements in forensic pathologic investigation. Apart from the accuracy and three dimensionality that conventional documentations lack, these techniques allow for the re-examination of the corpse and the crime scene even decades later, after burial of the corpse and liberation of the crime scene. We believe that this virtual, noninvasive or minimally invasive approach will improve forensic medicine in the near future.

An immunohistochemical study of the diagnostic value of TREM-1 as marker for fatal sepsis cases.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is produced and up-regulated by exposure of myeloid cells to lipopolysaccharides or other components of either bacterial or fungal origin, which causes it to be strongly expressed on phagocytes that accumulate in inflamed areas. Because TREM-1 participates in septic shock and in amplifying the inflammatory response to bacterial and fungal infections, we believe it could be an immunohistochemical marker for postmortem diagnosis of sepsis. We tested the anti-TREM-1 antibody in 28 cases of death by septic shock and divided them into two groups. The diagnosis was made according to the criteria of the Surviving Sepsis Campaign. In all cases, blood cultures were positive. The first group was comprised subjects that presented high ante-mortem serum procalcitonin and the soluble form of TREM-1 (s-TREM-1) values. The second group comprised subjects in which s-TREM-1 was not measured ante-mortem. We used samples of brain, heart, lung, liver and kidney for each case to test the anti-TREM-1 antibody. A semiquantitative evaluation of the immunohistochemical findings was made. In lung samples, we found immunostaining in the cells of the monocyte line in 24 of 28 cases, which suggests that TREM-1 is produced principally by cells of the monocyte line. In liver tissue, we found low TREM-staining in the hepatocyte cytoplasm, duct epithelium, the portal-biliary space and blood vessel. In kidney tissue samples, we found the TREM-1 antibody immunostaining in glomeruli and renal tubules. We also found TREM-1 staining in the lumen of blood vessels. Immunohistochemical staining using the anti-TREM-1 antibody can be useful for postmortem diagnosis of sepsis.

Preimplantation genetic diagnosis: a step by step guide to recent Italian ethical and legislative troubles.

OBJECTIVE: To analyse legislation and medical professionals' position concerning the doctor's role in assisted reproduction techniques in Italy, and to discuss the implications for physicians of preimplantation genetic diagnosis (PGD). BACKGROUND: Until recently a strict interpretation of the assisted reproduction law (40/2004) and the guidelines subsequently issued, lead to denying infertile couples affected by genetic diseases the right to resort to PGD. In October 2006 the Constitutional Court ruled regarding the question of the constitutional legitimacy of the prohibition of PGD. DISCUSSION: The Constitutional Court declared the manifest inadmissibility of the question of the constitutional legitimacy of article 13 of law 40/2004. The debate has become very animated since the ruling. After the negative sentence of the Constitutional Court, three further sentences recognised the right of couples to obtain PGD, representing a hard blow to law 40/2004 and to the ministerial guidelines; a further confirmation of the untenability of a law that violates fundamental principles such as the right to healthcare for women and the unborn child, the right to responsible motherhood and to informed consent. CONCLUSION: It seems that in Italy the legislative inadequacy for medically assisted procreation is reprieved by the courageous decisions of the judges, which refer to the values of the Italian Constitution, in defence of the fundamental rights of the citizens.

Scuba diving death: Always due to drowning? Two forensic cases and a review of the literature.

Scuba diving is an increasingly common recreational activity. We describe the physiopathology of barotrauma in two cases where death was caused by pulmonary barotrauma while diving. An inspection and autopsy were carried out in both cases. The autopsy data were supported by post-mortem radiological investigation. Histological and toxicological analyses were also carried out, and dive computer and tank manometer analysis performed. In both cases, the cause of death was attributable to arterial gas embolism, resulting from pulmonary barotrauma subsequent to pulmonary over-distension. The dive computer analysis and the tank manometer allowed us to understand what happened underwater. In our opinion, a multidisciplinary approach is crucial in order to clarify the cause of death. Some pathological conditions and risk factors should be considered before diving.

A systematic study of a myocardial lesion: colliquative myocytolysis.

BACKGROUND: The term "myocytolysis" was first used to define the repair process of contraction band necrosis associated with an acute myocardial infarction. On the other hand, in the latter condition a "myofibrillolysis," presenting edematous myocardial cells not involved by infarct necrosis, and without evidence of repair process was reported. The objective of this study is to establish the frequency, extent and meaning of this myocardial lesion. MATERIALS AND METHODS: In 12 groups of patients for a total of 432 cases with and without coronary heart disease, "colliquative myocytolysis"--i.e., progressive vacuolization by loss of myofibrils until their total or subtotal disappearance associated with intramyocellular edema in absence of any cellular reaction--was graded in 16 histological slides of the different cardiac regions in each pathological case. RESULTS: Colliquative myocytolysis (CM) was present in more than 90% with a maximal extent in cases of irreversible congestive heart failure followed by transplanted heart cases (67%) with a survival greater than 1 week. In all other groups, the lesion was absent or minimal. CONCLUSIONS: No correlation was found between CM and contraction band necrosis, gender, age, heart weight, myocardial fibrosis, coronary artery stenosis, clinical data. Colliquative myocytolysis is a specific histological marker of congestive heart failure, without relation to coronary blood flow, heart weight and myocardial fibrosis. Vacuolization of myocardial cells may be due to other causes (e.g., storage disease, etc.) or may be an artifact. There is no support for the belief that coronary ischemia or myocardial hypoxia is its causes.

Myocardial disarray: an architectural disorganization linked with adrenergic stress?

BACKGROUND: Myocardial disarray is a structural abnormality found in specific zones of the normal heart. In some conditions, such as hypertrophic cardiomyopathy (HCM), its occurrence represents a pathological process leading to myocardial asynergy. The incidence of "pathological" myocardial disarray in humans is still not known. It has been suggested that a link exists between adrenergic overactivity and myocardial disarray. The aim of the present study is to compare heart findings in conditions with and without chronic sympathetic overtone for evidence of possible linkage in humans. MATERIALS AND METHODS: A total of 340 hearts were studied. They were divided into seven groups: sudden/unexpected coronary death; sudden/unexpected death in silent Chagas' disease; brain haemorrhage following berry aneurysm rupture; transplanted hearts; congestive heart failure, AIDS and cocaine abuse. Findings in these hearts were compared with anatomic changes in 92 control hearts, where the decedent had died from head trauma, electrocution, or carbon monoxide intoxication. The frequency and presence of myocardial disarray were recorded and correlated to heart weight, extent of myocardial fibrosis, and contraction band necrosis (CBN). RESULTS: Hearts from patients with conditions that increased sympathetic tone showed an association of myocardial disarray and contraction band necrosis without any relationship to heart weight. CONCLUSIONS: Myocardial disarray was observed in cardiac areas where it is not found normally. It was associated with adrenergic myocardial stress morphologically expressed by a higher number of foci (p<0.01) and myocells (p<0.001) with CBN versus findings in normal subjects. The condition deserves further study as a possible myocardial asynergic and arrhythmogenic factor especially in sudden/unexpected death.

Type and extent of myocardial injury related to brain damage and its significance in heart transplantation: a morphometric study.

BACKGROUND: Focal myocardial necrosis reported in patients who died of brain lesions and in donor hearts soon after insertion has been attributed to catecholamine-related injury induced before operation, or in the perioperative period. Interpretation of the morphofunctional type of myocardial injury observed and its quantification may help understand both its pathophysiology and clinical relevance. METHODS: In 27 patients without heart disease who died of intracranial brain hemorrhage after berry aneurysm rupture, terminal clinical signs were correlated with the presence of absence of myocardial injury. All hearts were systematically examined, and the total histologic area was measured in square millimeters, with both the number of foci and myocardial cells showing necrosis, normalized to 100 mm2. Forty-five cases of fatal head trauma (26 "instantaneous" and 19 "rapid" deaths) in normal subjects and 38 cases of acquired immunodeficiency syndrome with (14 cases) or without (24 cases) severe brain damage were used as control subjects. RESULTS: Contraction band necrosis was the only form of myocardial necrosis found in 89% of patients with acute brain hemorrhage. Its extent was 26 +/- 34 foci and 67 +/- 104 necrotic myocardial cells x 100 mm2. In patients with acquired immunodeficiency syndrome, its frequency was 58% in those without and 78.5% with severe brain lesions, with foci and myocardial cell values of 1 +/- 1.5 and 10 +/- 22 and 7 +/- 16 and 17 +/- 32, respectively. In head trauma cases with instantaneous death, the frequency was 4% (one case only with foci 0.5 and myocardial cells 35), whereas with a rapid death it was 40% (foci 12 +/- 18 and myocardial cells 21 +/- 33). CONCLUSIONS: The observed myocardial injury was present in all groups examined, being maximal in patients with intracranial brain hemorrhage with longer survival and minimal in patients with head trauma who died instantaneously. In this setting, this lesion is typical of catecholamine myotoxicity and may express a sympathetic overstimulation either in the agonal period and independent of therapy or be caused by brain injury, especially intracranial brain hemorrhage. However, the extent of myocardial injury observed was minimal and should not jeopardize cardiac function if hearts from such subjects are transplanted.

Kidney vascular damage and cocaine.

Cardiovascular damage is common in young cocaine addicts, and similar atherosclerotic lesions seem likely in the kidneys. To confirm this hypothesis, we performed histological examination of 40 kidney autopsy specimens classified as "cocaine-related deaths"; as controls, kidney specimens of 40 road accident victims were examined. Semiquantitative analysis showed that the ratio of the number of glomeruli affected by hyalinosis to the total number of glomeruli was 0.09 +/- 0.13 in addicts and 0.005 +/- 0.01 in controls; the difference was highly significant. The degree of periglomerular fibrosis was significantly higher in cocaine addicts than in accident victims. The ratio of glomeruli to tubular casts was 0.15 +/- 0.17 in cocaine addicts and 0.17 +/- 0.18 in controls (not significant). The degree of interstitial cellular infiltration was significantly higher in addicts than controls. A monunuclear cell infiltrate was observed prevalently in the medullary region. Arteriolar sclerosis was significantly higher in addicts than controls. Medial thickening, luminal narrowing and vessel obstruction were absent in the control group. Quantitative morphometric analysis of arterial structure showed significantly greater lumen circumference, intima circumference, media circumference, intima area, media area, intima thickness and media thickness in cocaine addicts than in controls.

Anabolic steroid abuse and cardiac sudden death: a pathologic study.

CONTEXT: Androgenic anabolic steroids (AAS) used for improving physical performance have been considered responsible for acute myocardial infarction and sudden cardiac death. OBJECTIVE: To establish the relationship between AAS and cardiac death. DESIGN: Case report. PATIENTS: Two young, healthy, male bodybuilders using AAS. MAIN OUTCOME MEASURES: Pathologic cardiac findings associated with AAS ingestion. RESULTS: The autopsy revealed normal coronary arteries. In one case, we documented a typical infarct with a histologic age of 2 weeks. A segmentation of myocardial cells at the intercalated disc level was observed in the noninfarcted region. This segmentation was the only anomaly detected in the second case. No other pathologic findings in the heart or other organs were found. Urine in both subjects contained the metabolites of nortestosterone and stanozolol. COMMENT: A myocardial infarct without vascular lesions is rare. To our knowledge, its association with AAS use, bodybuilding, or both lacks any evidence of a cause-effect relationship. The histologic findings in our 2 cases and in the few others reported in medical literature are nonspecific and do not prove the cardiac toxicity of AAS. A better understanding of AAS action on the neurogenic control of the cardiac function in relation to regional myocardial contraction and vascular regulation is required.

Fatal anaphylactic shock during a fluorescein angiography.

The Authors describe an extremely rare fatal case (sixth case in the literature) of anaphylactic shock following a fluorescein angiography. This is the first report in which the diagnosis of anaphylactic reaction to the dye was made through laboratory analyses. The diagnosis of fatal shock due to sodium fluorescein was made based on clinical, laboratory and immunohistochemical data. Mast-cell tryptase was dosed in serum and a pulmonary immunohistochemical evaluation was performed. Tryptase, a neutral protease of human mast-cells is a potentially important indicator of mast-cell involvement in anaphylactic events.

Adam (MDMA) and Eve (MDEA) misuse: an immunohistochemical study on three fatal cases.

Three fatal cases of MDMA/MDEA misuse have been examined. These referred to white males between 19 and 20 years of age, in which post-mortem toxicology showed the presence of MDMA (in one case), MDEA (in one case) and both (in one case). The clinical data were analysed and the histopathological findings were studied following immunohistochemical investigations. A complete immunohistochemical study has made it possible to demonstrate rhabdomyolysis and myoglobinuria with alterations of the organs typical of a DIC. Clinical, histopathological and toxicological data suggest that severe or fatal complications following ecstasy ingestion could be related to idiosyncratic response.

Immunohistochemical quantification of pulmonary mast-cells and post-mortem blood dosages of tryptase and eosinophil cationic protein in 48 heroin-related deaths.

Recent studies suggest that many fatal heroin overdoses are caused by anaphylactoid reaction. In the present study we measured tryptase and eosinophil cationic protein in post-mortem blood of 48 deaths after heroin injection. We also investigated the presence and pulmonary distribution of mast-cells using specific immunohistochemical antibody for tryptase and morphometric evaluation in those cases of heroin-related deaths. The data were compared with 44 subjects who died following head trauma and to 32 cases of fatal anaphylactic shock. In the heroin-related death cases, the measurements of serum tryptase levels and eosinophil cationic protein dosages resulted in particularly elevated concentrations compared with the trauma cases. Nevertheless, the data that our study supplies by immunohistochemical techniques indicate that when mast-cells count in the lung was determined, no definite pattern was obtained between fatal heroin overdose cases and the control groups. Furthermore, the wide range of morphine concentrations found in post-mortem blood samples suggest that the term 'overdose' is relative and does not sufficiently characterize death associated with heroin addiction. Our study confirms that elevated concentrations of serum tryptase are associated with many heroin-related deaths. At this moment to attribute the cause of these deaths to 'heroin overdose' ignores the likely causal contribution of other possible systemic reactions to the mechanism of death.

1H-NMR studies of postmortem biochemical changes in rat skeletal muscle.

1H-nuclear magnetic resonance (NMR) has been applied to the study of postmortem biochemical changes in perchloric acid extracts of rat skeletal muscle. Several metabolites have been detected and the dependence upon the postmortem time has been considered. The simultaneous quantitative determination of metabolites showing up at very low and very high fields has been suggested to yield a satisfactory delineation of the thanatochronology.

Histological criteria for diagnosis of amanita phalloides poisoning.

Five fatal cases of poisoning from ingestion of Amanita phalloides, a very common mushroom in central Italy, are reported. The fact that four of the cases occurred simultaneously enabled uniform collection of clinical, pathology and toxicology data, which is presented with particular emphasis on the histological aspects. The fifth case involved a six-year-old girl, and is discussed with reference to differential diagnosis with respect to Reye's syndrome, which was the initial diagnosis, demonstrated incorrect by the histology, pathology and toxicology findings. The typical liver and kidney alterations of Amanita phalloides poisoning, consisting of massive hepatic central lobular cell necrosis and acute tubular necrosis of the kidney are described. Outside the liver, there was often general hemorrhagic diathesis and severe brain edema. Although poisoning by Amanita phalloides is rare, these cases confirm the requirement for as complete a comparison as possible between circumstantial histopathological and toxicological data for the purposes of forensic diagnosis.