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

Reliable diagnoses of sepsis remain challenging in forensic pathology routine despite improved methods of sample collection and extensive biochemical and immunohistochemical 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 translocation. Lastly, peripheral and cardiac blood may be unavailable during autopsy. Procalcitonin, C-reactive protein, and interleukin-6 can be measured in biological fluids collected 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 biomarkers could more effectively discriminate non-infectious from infectious inflammations. In this article, we propose a review of the literature pertaining to the diagnostic performance of classical and novel biomarkers of inflammation and bacterial infection in the forensic setting

Confirmation of natural gas explosion from methane quantification by headspace gas chromatography-mass spectrometry (HS-GC-MS) in postmortem samples: a case report

A new analytical approach for measuring methane in tissues is presented. For the first time, the use of in situ-produced, stably labelled CDH3 provides a reliable and precise methane quantification. This method was applied to postmortem samples obtained from two victims to help determine the explosion origin. There was evidence of methane in the adipose tissue (82nmol/g) and cardiac blood (1.3nmol/g) of one victim, which corresponded to a lethal methane outburst. These results are discussed in the context of the available literature to define an analysis protocol for application in the event of a gas explosio

Will Widespread Synthetic Opioid Consumption Induce Epigenetic Consequences in Future Generations?

A growing number of evidence demonstrates that ancestral exposure to xenobiotics (pollutants, drugs of abuse, etc.) can perturb the physiology and behavior of descendants. Both maternal and paternal transmission of phenotype across generations has been proved, demonstrating that parental drug history may have significant implications for subsequent generations. In the last years, the burden of novel synthetic opioid (NSO) consumption, due to increased medical prescription of pain medications and to easier accessibility of these substances on illegal market, is raising new questions first in term of public health, but also about the consequences of the parental use of these drugs on future generations. Besides being associated to the neonatal abstinence syndrome, <i>in utero</i> exposure to opioids has an impact on neuronal development with long-term repercussions that are potentially transmitted to subsequent generations. In addition, recent reports suggest that opioid use even before conception influences the reactivity to opioids of the progeny and the following generations, likely through epigenetic mechanisms. This review describes the current knowledge about the transgenerational effects of opioid consumption. We summarize the preclinical and clinical findings showing the implications for the subsequent generations of parental exposure to opioids earlier in life. Limitations of the existing data on NSOs and new perspectives of the research are also discussed, as well as clinical and forensic consequences

Stability of postmortem methemoglobin: Artifactual changes caused by storage conditions.

Hemoglobin is the protein in red blood cells that carries and distributes oxygen to the body. Methemoglobinemia is a blood disorder in which an abnormal amount of methemoglobin (MetHb), a form of hemoglobin (Hb), is produced from either inadequate MetHb reductase activity or too much MetHb production or by exposure to oxidizing agents. This could lead to anoxia and death if it is not treated. However, this parameter has not been investigated as a valid post-mortem indicator because random MetHb levels have been observed in various studies: MetHb increases can be observed due to autoxidation during storage, and MetHb decreases can be observed due to MetHb reductase or microbial activity in post-mortem samples. MetHb variations can also come from the blood state and can interfere in the optical measurements of MetHb. We have studied the post-mortem MetHb concentrations according to various storage conditions. Based on our results, both the post-mortem delay and the delay before analysis should be reduced whenever possible to avoid changes in MetHb. If the analysis is delayed for a short period of time (two weeks), the blood sample taken at autopsy should not be frozen but collected in EDTA preservative and stored under refrigeration (4-6°C) until analysis. If the analysis is delayed for a longer period (more than two weeks), the blood sample should be frozen with cryoprotectant at -80°C or -196°C

Significant postmortem diffusion of ethanol: A case report.

In the realm of forensic pathology, ethanol is one of the most frequently encountered xenobiotics. The determination of ethanol concentration in blood after death is of great interest in forensic settings. It is important to be able to determine the level of intoxication of the deceased at the time of death, which is directly correlated to the ability to act prior to death, especially when a suicide is suspected. This estimation is not always easy to establish owing to various artifacts that are important to know for a proper ethanol blood level interpretation, among them postmortem (PM) diffusion. We describe here a case of unusual ethanol distribution in body compartments and discuss the importance of PM diffusion and redistribution while performing complementary toxicological analysis, especially when the blood and urine samples seemed to be inconsistent after the first results

A preclinical model for identifying rats at risk of alcohol use disorder.

Alcohol use is one of the world's leading causes of death and disease, although only a small proportion of individuals develop persistent alcohol use disorder (AUD). The identification of vulnerable individuals prior to their chronic intoxication remains of highest importance. We propose here to adapt current methodologies for identifying rats at risk of losing control over alcohol intake by modeling diagnostic criteria for AUD: inability to abstain during a signaled period of reward unavailability, increased motivation assessed in a progressive effortful task and persistent alcohol intake despite aversive foot shocks. Factor analysis showed that these three addiction criteria loaded on one underlying construct indicating that they represent a latent construct of addiction trait. Further, not only vulnerable rats displayed higher ethanol consumption, and higher preference for ethanol over sweetened solutions, but they also exhibited pre-existing higher anxiety as compared to resilient rats. In conclusion, the present preclinical model confirms that development of an addiction trait not only requires prolonged exposure to alcohol, but also depends on endophenotype like anxiety that predispose a minority of individuals to lose control over alcohol consumption

Toxicity assessment of refill liquids for electronic cigarettes.

We analyzed 42 models from 14 brands of refill liquids for e-cigarettes for the presence of micro-organisms, diethylene glycol, ethylene glycol, hydrocarbons, ethanol, aldehydes, tobacco-specific nitrosamines, and solvents. All the liquids under scrutiny complied with norms for the absence of yeast, mold, aerobic microbes, Staphylococcus aureus, and Pseudomonas aeruginosa. Diethylene glycol, ethylene glycol and ethanol were detected, but remained within limits authorized for food and pharmaceutical products. Terpenic compounds and aldehydes were found in the products, in particular formaldehyde and acrolein. No sample contained nitrosamines at levels above the limit of detection (1 μg/g). Residual solvents such as 1,3-butadiene, cyclohexane and acetone, to name a few, were found in some products. None of the products under scrutiny were totally exempt of potentially toxic compounds. However, for products other than nicotine, the oral acute toxicity of the e-liquids tested seems to be of minor concern. However, a minority of liquids, especially those with flavorings, showed particularly high ranges of chemicals, causing concerns about their potential toxicity in case of chronic oral exposure

The postmortem diagnosis of alcoholic ketoacidosis.

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