Showing papers by "Cristian Palmiere published in 2014"

Postmortem diagnosis of hypothermia

Abstract: The identification of hypothermia as the cause of death has always been somewhat problematic in forensic pathology because of unspecific, inconstant, or even negative macroscopic and microscopic findings. Though the simultaneous presence of frost erythema, Wischnewski spots, hemorrhages into the synovial membrane, bloody discoloration of synovial fluid of the knee, and basal vacuolization of the renal tubular epithelial cells has been indicated as strongly supportive of fatal hypothermia, their absence does not allow the diagnosis of hypothermia to be ruled out. Postmortem biochemical investigations are valuable in detecting adaptation responses to cold stress and metabolic changes that occur following cold exposure. However, ethanol intoxication prevents appearance of adaptation responses to cold, rendering the diagnosis less obvious. Immunohistochemistry, postmortem imaging, and molecular pathology have shown promising results, although at present, they do not provide pathognomonic signs of fatal hypothermia. The aim of this article is to present a review of the literature covering the significance of different postmortem investigations that are associated with hypothermia fatalities.

Markers for sepsis diagnosis in the forensic setting: state of the art.

Abstract: Reliable diagnoses of sepsis remain challenging in forensic pathology routine despite improved methods of sample collection and extensive biochemical and im- munohistochemical investigations. Macroscopic findings may be elusive and have an infectious or non-infectious origin. Blood culture results can be difficult to interpret due to postmortem contamination or bacterial transloca- tion. Lastly, peripheral and cardiac blood may be unavail- able during autopsy. Procalcitonin, C-reactive protein, and interleukin-6 can be measured in biological fluids collect - ed during autopsy and may be used as in clinical practice for diagnostic purposes. However, concentrations of these parameters may be increased due to etiologies other than bacterial infections, indicating that a combination of bi- omarkers could more effectively discriminate non-infec- tious from infectious inflammations. In this article, we pro - pose a review of the literature pertaining to the diagnostic performance of classical and novel biomarkers of inflam- mation and bacterial infection in the forensic setting.

The Postmortem Diagnosis of Alcoholic Ketoacidosis

Abstract: Aims: The aim of this article is to review the forensic literature covering the postmortem investigations that are associated with alcoholic ketoacidosis fatalities and report the results of our own analyses. Methods: Eight cases of suspected alcoholic ketoacidosis that had undergone medico-legal investigations in our facility from 2011 to 2013 were retrospectively selected. A series of laboratory parameters were measured in whole femoral blood, postmortem serum from femoral blood, urine and vitreous humor in order to obtain a more general overview on the biochemical and metabolic changes that occur during alcoholic ketoacidosis. Most of the tested parameters were chosen among those that had been described in clinical and forensic literature associated with alcoholic ketoacidosis and its complications. Results: Ketone bodies and carbohydrate-deficient transferrin levels were increased in all cases. Biochemical markers of generalized inflammation, volume depletion and undernourishment showed higher levels. Adaptive endocrine reactions involving insulin, glucagon, cortisol and triiodothyronine were also observed. Conclusions: Metabolic and biochemical disturbances characterizing alcoholic ketoacidosis can be reliably identified in the postmortem setting. The correlation of medical history, autopsy findings and biochemical results proves therefore decisive in identifying pre-existing disorders, excluding alternative causes of death and diagnosing alcoholic ketoacidosis as the cause of death.

A case of suicide by ingestion of caffeine.

Abstract: Intentional or unintentional caffeine abuse due to excessive intake of beverages or energy drinks containing caffeine is relatively frequent. However, death due to caffeine intoxication is rare and case reports of fatalities from caffeine toxicity are relatively infrequent. In this report, we describe an autopsy case involving a 31 year-old man who intentionally took a large amount of caffeine tablets in the form of a weight loss supplement as part of a suicide plan. Caffeine femoral blood concentration (170 mg/l) was within the toxic and potentially lethal ranges reported in the literature in similar cases. Postmortem biochemistry results suggested depressed glomerular filtration rate and pre-renal failure at the time of death but failed to reveal myoglobinuria, glycosuria, ketonuria or ketonemia. Based on the absence of pathological findings at autopsy and the high blood caffeine level, death was attributed to acute caffeine toxicity. The case emphasizes the usefulness of performing exhaustive toxicology and searching for all potentially relevant information in order to formulate appropriate hypotheses concerning the cause and manner of death.

Allergic reactions following contrast material administration: nomenclature, classification, and mechanisms.

Abstract: In forensic pathology routine, fatal cases of contrast agent exposure can be occasionally encountered. In such situations, beyond the difficulties inherent in establishing the cause of death due to nonspecific or absent autopsy and histology findings as well as limited laboratory investigations, pathologists may face other problems in formulating exhaustive, complete reports, and conclusions that are scientifically accurate. Indeed, terminology concerning adverse drug reactions and allergy nomenclature is confusing. Some terms, still utilized in forensic and radiological reports, are outdated and should be avoided. Additionally, not all forensic pathologists master contrast material classification and pathogenesis of contrast agent reactions. We present a review of the literature covering allergic reactions to contrast material exposure in order to update used terminology, explain the pathophysiology, and list currently available laboratory investigations for diagnosis in the forensic setting.

Risk factors in fatal cases of anaphylaxis due to contrast media: a forensic evaluation.

Abstract: Background: Fatalities following contrast medium exposure are extremely rare in clinical routine, though they may occur as an exception. Some may fall under the purview of the inquiring authorities and forensic pathologists due to their in-hospital occurrence. The purpose of this study was to assess the risk factors for anaphylaxis due to contrast medium administration that can be identified in fatal cases. Methods: Fatalities occurred during the course of clinical investigations with contrast media described in the literature and fatal reactions to contrast agents that had undergone forensic investigations in our medicolegal center were reviewed with respect to patient characteristics, administered contrast medium, performed biochemical investigations and potential risk factors identified based on clinical history and medical records. Results: Biochemical investigations into the fatal cases examined in our facility revealed increased mast cell tryptase, total IgE and activated mast cells in all subjects. Data obtained from the literature and our own investigations indicated that in only a minority of the fatal cases had there been previous exposure to contrast compounds, while most cases of severe anaphylaxis involved patients who apparently reacted on initial exposure. Conclusions: Most fatal cases failed to present any identifiable predisposing conditions out of those traditionally considered as risk factors for an anaphylactic reaction to contrast compounds in the medical histories of the patients. Comprehensive clinical histories and thorough reviews of medical data, along with exhaustive forensic investigations, provide information that is relevant in order to better appreciate the interwoven relationships linking all factors potentially involved in the pathogenesis of fatal anaphylaxis to contrast media.

Postmortem findings in bone cement implantation syndrome-related deaths.

Abstract: Several mechanisms have been postulated as potentially involved in life-threatening complications during cemented surgery. In this study, we evaluated the role of anaphylaxis and pulmonary fat embolism in the pathophysiology of bone cement implantation syndrome in a series of fatal cases that underwent medicolegal investigations. Postmortem findings in these cases were compared with those obtained from individuals who died after other injuries and/or interventions and in which activated mast cells and pulmonary fat embolism were involved in the pathogenesis of death. Fifty subjects were selected including 6 individuals who had undergone cemented total hip arthroplasty and died intraoperatively, 32 subjects who died shortly after being involved in traffic accidents, 8 individuals who died shortly after the injection of contrast material, and 4 subjects who had undergone orthopedic surgery and died postoperatively. Massive pulmonary fat embolism was determined to be the cause of death in all the 6 subjects who died intraoperatively as well as the main cause of death in traffic-road victims with rapid respiratory function deterioration. Mast cell activation was identified exclusively in the group of subjects who died shortly after contrast material administration. Massive pulmonary fat embolism appears to be the most important factor responsible for severe cardiorespiratory function deterioration during cemented arthroplasty. Cardiac comorbidities can also significantly influence the severity of intraoperative complications, thus corroborating the hypothesis of a multifactorial model in the pathogenesis of bone cement implantation syndrome.

Fatal metformin overdose: case report and postmortem biochemistry contribution.

Abstract: Metformin is an oral antihyperglycemic agent used in the management of type 2 diabetes mellitus. Lactic acidosis from metformin overdose is a rare complication of metformin therapy and occurs infrequently with therapeutic use. Fatal cases, both accidental and intentional, are extremely rare in clinical practice. Metformin is eliminated by the kidneys, and impaired renal function can result in an increased plasma concentration of the drug. In this report, we describe an autopsy case involving a 70-year-old woman suffering from diabetes mellitus and impaired renal function who received metformin treatment. Metformin concentrations in the peripheral blood collected during hospitalization and femoral blood collected during autopsy were 42 and 47.3 µg/ml, respectively. Lactic acidosis (29.10 mmol/l) was objectified during hospitalization. Furthermore, postmortem biochemistry allowed ketoacidosis to be diagnosed (blood β-hydroxybutyrate, 10,500 µmol/l). Death was attributed to lactic acidosis due to metformin intoxication. Increased plasma concentrations of the drug were attributed to severely impaired renal function. The case emphasizes the usefulness of performing exhaustive toxicology and postmortem biochemistry towards the more complete understanding of the pathophysiological mechanisms that may be involved in the death process.

Diagnostic performance of urinary metanephrines for the postmortem diagnosis of hypothermia

Abstract: The purpose of this study was to assess the diagnostic potential of urinary metanephrines and 3-methoxytyramine compared to urinary catecholamine determination in diagnosing antemortem cold exposure and fatal hypothermia. 83 cases of fatal hypothermia and 144 control cases were included in this study. Catecholamines (adrenaline, noradrenaline and dopamine), metanephrines (metanephrine, normetanephrine) and 3-methoxytyramine were measured in urine collected during autopsy. All tested analytes were significantly higher in hypothermia cases compared to control subjects and displayed a generally satisfying discriminative value, thus indicating urinary catecholamines and their metabolites as reliable markers of cold-related stress and hypothermia related-deaths. Metanephrine and adrenaline had the best discriminative value between hypothermia and control cases compared to other tested analytes, though with different sensitivity and specificity. These can therefore be considered the most suitable markers of cold-related stress.

Fatal intrahepatic hemorrhage after nadroparin use for total hip arthroplasty.

Abstract: Low-molecular-weight heparins have become the predominant choice for deep venous thrombosis prophylaxis and treatment. However, their use may cause bleeding complications. Intrahepatic bleeding is exceptional and only very few cases have been described. The authors present a unique case of fatal intrahepatic hematoma complicating nadroparin use in a 65-year-old woman with a hepatic cyst who was admitted to hospital for unilateral total hip arthroplasty. At autopsy, hemoperitoneum (2,000 ml of blood and clots) was evident. A ruptured sub-capsular hematoma involving the right lobe of the liver was observed. The hemorrhage within the cyst induced by the nadroparin use was likely responsible for the subsequent hepatic hematoma, liver rupture, and death. This case highlights the need for pathologists and surgeons to be aware of the possibility of intrahepatic hematoma in patients who have received low-molecular-weight heparins, undergone major surgery and present postoperative hemodynamic instability, especially in those with preoperative diagnosis of hepatic cyst.

Post-mortem diagnosis of malaria

Abstract: Dear Editor Sudden unexpected deaths due to imported malaria occasionally occur in non-endemic areas and can lead to forensic issues 1–4. Post-mortem identification of malaria in non-endemic countries is challenging because pathologists do not often encounter cerebral malaria 5,6 and because the infection is rarely documented ante-mortem. Post-mortem diagnosis of malaria is often only done when there is a suspicion based on anamnesis or available medical information. Unfortunately, medical records are generally incomplete, unreliable or absent when bodies are admitted to the mortuary for medico-legal investigations. Moreover, macroscopic findings at necropsy are often non-specific 7,8. Here, we report a post-mortem diagnosis of malaria, completely unsuspected clinically. Briefly, a previously healthy 48-year-old Caucasian woman travelled to Ivory Coast with her husband, spending 3 weeks in the southern forest zone. They had taken chloroquine weekly for malaria chemoprophylaxis only before travelling to Africa, due to misunderstanding the medical advice. Three days before returning to Switzerland, she suffered abrupt onset of fever, chills, malaise and muscle aches. Due to flu-like symptoms, she self-medicated with aspirin. Four days after returning from Africa, she was found dead at home. As a result of the unclear death, a medico-legal autopsy was ordered by the prosecutor and performed the same day. Post-mortem investigations revealed essentially pulmonary oedema, hepatomegaly (2215 g) and splenomegaly (380 g). Toxicology failed to detect common illicit or prescribed drugs. Biochemistry showed increased C-reactive protein (84 mg/L) and procalcitonin (5.08 μg/L). Microbiology failed to detect any underlying bacterial infections. Given the high suspicion of malaria, urine, vitreous humour, pericardial fluid, blood, liver and brain samples were examined using Plasmodium falciparum, Plasmodium malariae, Plasmodium vivax and Plasmodium ovale real-time PCRs 9,10. Plasmodium falciparum was confirmed in these samples (Table​(Table1).1). Estimated parasitaemia was 15.2% (760 000 parasites/μL in blood), considering that 50 000 parasites/μL correspond to 1% of parasitaemia 10. Table 1 Quantification by real-time PCR specific for Plasmodium falciparum in the different samples investigated Neuropathology showed cerebral oedema (1370 g), grey and white matter with congested vessels containing numerous parasitized erythrocytes with malarial pigment filling the vascular lumen, confirming that the death was due to cerebral malaria. Erythrocytes with malarial pigment were found within dilated vessels in the lungs, myocardium, liver, kidneys and spleen. In conclusion, malaria is probably an under-recognized aetiology of sudden death in non-endemic countries. In the present case, malaria was only suspected based on the history of recent travel to sub-Saharan Africa, allowing the appropriate investigations to be performed. PCR and Giemsa staining allowed pathologists to confirm the diagnosis and to determine the severity of the disease. This case report underlies the importance of anamnesis in forensic settings. When no information is available and cause of death is not identified, malaria should be considered as a potential aetiology. Moreover, this case underlines the importance of precise advice at the time of anti-malaria chemoprophylaxis prescription, because (1) this patient unfortunately understood that the chloroquine prophylaxis should only be taken before travelling as a preventive measure, and (2) the patient did not ask for medical advice when suffering over several days from a flu-like syndrome, despite her history of travel to a country where malaria is endemic.

Alcoholic Ketoacidosis as the cause of death: Thomsen and co-workers came first.

Abstract: Thomsen et al. (1993) published an extremely interesting and innovative preliminary communication in Forensic Science International, vol. 60 (1993), in which they presented the results of a forensic study performed on 27 alcoholics with known causes of death, 16 alcoholics with unknown causes of death and 79 control subjects. The determination of blood acetone + acetoacetate revealed significantly increased levels in alcoholics with unknown causes of death compared with the other studied groups. Based on these findings, the authors concluded that their results strongly indicated ketoacidosis as the sole or contributing cause of death in chronic alcoholics with negative postmortem investigation results. In Forensic Science International, vol. 62 (1993), Denmark (1993) reported the results of …

Philemon and Baucis Deaths: Case Reports and Postmortem Biochemistry Contribution

Abstract: The death of a person as a reaction to the death of another is known as Philemon and Baucis death and may represent a difficult challenge for pathologists, especially due to the decompositional changes that often characterized these situations. In this article, we describe two cases of Philemon and Baucis deaths, the first concerning a married couple and the second concerning a father and son. Postmortem investigations including radiology and biochemistry were performed. Based on the results of all investigations, deaths were attributed to natural causes. Third-party involvement could be excluded in both situations. In one case, biochemical analysis results revealed potentially contributing causes of death. The reported cases emphasize the importance of correlating findings from different postmortem investigations to identify causes of death, precipitating conditions and predisposing disorders, thus allowing the conclusion of natural death to be reached and third-party involvement to be excluded.

LETTER TO THE EDITOR Alcoholic Ketoacidosis as the Cause of Death: Thomsen and Co-workers Came First

Abstract: Thomsen et al. (1993) published an extremely interesting and innovative preliminary communication in Forensic Science International, vol. 60 (1993), in which they presented the results of a forensic study performed on 27 alcoholics with known causes of death, 16 alcoholics with unknown causes of death and 79 control subjects. The determination of blood acetone + acetoacetate revealed significantly increased levels in alcoholics with unknown causes of death compared with the other studied groups. Based on these findings, the authors concluded that their results strongly indicated ketoacidosis as the sole or contributing cause of death in chronic alcoholics with negative postmortem investigation results. In Forensic Science International, vol. 62 (1993), Denmark (1993) reported the results of a study focusing on betahydroxybutyrate as a marker for sudden death in chronic alcoholics. Denmark measured beta-hydroxybutyrate concentrations in vitreous humor and urine. In 6 out of 49 studied subjects, the author found vitreous beta-hydroxybutyrate levels ranging from 19 to 26.9 mg/dl and urine betahydroxybutyrate values ranging from 26.7 to 493 mg/dl. In all these six cases, death was initially thought to be related to chronic alcohol abuse and no specific causes of death were obtained based on postmortem investigation findings. Demark concluded that increased beta-hydroxybutyrate concentration might suggest alcoholic ketosis in subjects with a history of chronic alcoholism, even in those in which previous withdrawal seizures were documented, and therefore be useful in explaining the death. Nevertheless, Denmark emphasized that other situations such as diabetic ketoacidosis and starvation could be responsible for metabolic changes potentially leading to marked ketosis. Professor Thomsen and his research team provided an extraordinary contribution to the identification of alcoholic ketoacidosis as the main or contributing cause of death in chronic alcoholics with negative postmortem investigation results (Thomsen et al., 1993, 1995, 1997; Thomsen and Frohlich, 1995; Thomsen, 1996). In addition, it cannot be denied that the preliminary communication published in Forensic Science International, vol. 60 (1993), preceded Denmark’s article in Forensic Science International, vol. 62. We sincerely apologize to Professor Thomsen, who can be rightly considered the first published author in the medico-legal setting to have seen the connection between alcoholic ketoacidosis and the cause of death in autopsy cases with inconclusive findings. Quantitative analysis of acetone, acetoacetate, beta-hydroxybutyrate and isopropyl alcohol is routinely performed in our facility in Lausanne, along with determination of vitreous glucose, blood glycated hemoglobin and numerous other biochemical parameters. On the other hand, the systematic application of postmortem biochemical investigations in general, and the application of analyses pertaining to glucose and free fatty acid metabolism specifically, in conventional and alternative postmortem samples, allowed us to obtain interesting data that proved useful in the postmortem diagnosis of death by hypothermia and alcoholic ketoacidosis. Biochemical investigations performed in samples collected during autopsy also enabled the determination of diabetic ketoacidosis as the main cause of death in previously unsuspected diabetics to be made as well as the identification of diabetic ketoacidosis-related deaths in situations with apparently conclusive autopsy and toxicology findings (Palmiere et al., 2013a,b). We would like to thank Professor Thomsen and his research team, firstly, for having demonstrated that alcoholic ketoacidosis should always be considered a possible cause of death in chronic alcohol abusers with otherwise unascertained causes of death, and secondly, for having shown that postmortem biochemical investigations can allow the conclusion of alcoholic ketoacidosis as the cause of death to be reached, thereby allowing alternative causes of death to be excluded.