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Background A proper antalgic treatment is based on the use of titrated drugs to provide adequate relief and a good tolerability profile. Therapies have a variable effectiveness among subjects depending on medical and genetic conditions. CYP2D6 variations determine a different clinical response to most analgesic drugs commonly used in daily clinical practice by influencing the drugs' pharmacokinetics. This study was a monocentric clinical trial exploring the CYP2D6 variants in 100 patients with a diagnosis of chronic pain. Methods DNA was extracted to evaluate the genotype and to classify patients as normal-fast (gNMs-F), normal-slow (gNMs-S), ultrarapid (gUMs), intermediate (gIMs), and poor metabolizers (gPMs) using the Activity Score (AS). Information on therapies and general side effects experienced by patients was collected. Nongenetic co-factors were evaluated to examine the discrepancy between metabolic profile predicted from genotype (gPh) and metabolic profile (phenocopying). Results The distribution of our data underlined the prevalence of the gNMs-F (67%), whereas gNMs-S were 24%, gIMs 6%, gPMs 3%, and no gUMs were found, resulting in 33% of patients with reduced metabolic activity. In the analyzed population sample, 86% and 56% of patients, respectively, took at least one or two drugs inhibiting in vitro activity of the CYP2D6 enzyme. Conclusions Over one-third of the enrolled patients showed altered CYP2D6 enzymatic metabolic activity, with a risk of phenocopying potentially due to polypharmacology. Trial registration ClinicalTrials.gov ID: NCT03411759. [ABSTRACT FROM AUTHOR]

• A case of complex suicide associated to the killing of a pet is presented. • The term peticide , as the combination of "pet" and "homicide" is proposed. • Two different suicide methods, intoxication and strangulation have been identified. • An occupation related suicide was supposed in light of victim's professional skills. The combined event of a suicide and the killing of a pet has been hardly explored in forensic literature, but it is not rare at all. In the reported case the dead corpse of a 60-year old mentally ill woman and the carcass of a dog were found on the bed of a private apartment. In light of death scene investigation, necroscopic examination and toxicological analyses death was attributed to licit drug intoxication and self-strangulation after lethal poisoning of the dog. Due to the presence of two lethal means (cervical noose and drugs), acting in chronological order, the event was classified as a secondary complex suicide. Moreover, the woman, although mentally ill, was a psychiatrist. Thus, her professional background, namely the easy access to psychiatric drugs together with her knowledge of drug composition and properties lead to suppose an occupation related suicide. The comprehensive analysis of all the available information, including death scene investigation, occupational, necroscopic and toxicological data, resulted of the utmost importance for a proper reconstruction of the events and are recommended in complex cases such as occupation related planned complex suicides combined to the killing of pets. [ABSTRACT FROM AUTHOR]

Major interplaying causes of heat stroke (HS) and fatal hyperthermia are climate, physical activity, artificial extreme ambient temperatures, confinement in a small compartment, and effects of drugs and chemicals, combined with predispositions and complications. A common and unfortunate cause of HS is vehicular hyperthermia (VH) death. Hyperthermia in a vehicle is a type of environmental thermal disorder, involving victim's susceptibility, confinement with restraint, and possible influences of drugs and poisons, including exhaust gas containing complex fumes, carbon dioxide and monoxide. Whereas VH typically occurs when babies or young children are being left unattended in parked vehicles in direct sunlight, it has been reported only anecdotally for adult subjects. Three cases of adult fatal VH will be herein presented. In each presented case the corpse was found enclosed in a vehicle on spring/summer days. During crime scene investigation (CSI) psychoactive substances were found near to the corpses leading to the suspect of a suicidal fatal drug intoxication. Basing on this misleading suspect in Case 2 and 3 a forensic expert was not charged for the CSI and a fatal VH was not suspected nor properly investigated. Later, a comprehensive autopsy, including biochemical and toxicological analyses, excluded a death related to natural causes, fatal intoxications, ketoacidosis and traumas. On the other hand, the reconstruction of the temperature, the humidity, the heat index and the related risk of HS allowed the diagnosis of fatal VH in all the reported cases. In particular, death occurred because of the long-lasting stay into a hot parked vehicle which was facilitated from self-administration of psychoactive drugs with related neuro-depression. This case series confirms that a comprehensive CSI followed by an autopsy including histology, biochemical and toxicological analysis remains mandatory in cases of forensic interest, as well as when a corpse is found enclosed in a vehicle. Anyway, sometimes the diagnosis of heat-related fatalities remains a medley of investigative and medicolegal observations. [ABSTRACT FROM AUTHOR]

• Acute myocarditis is related to a relevant number of sudden deaths. • Diagnosis is often performed post-mortem and on a forensic setting. • Eosinophilic myocarditis (EM) is a rare form of myocarditis. • Extensive myocardial sampling is mandatory for diagnosis of EM. • It's important to consider EM, although infrequent, facing with a sudden death. Acute myocarditis is related to a significant number of sudden deaths among young adults and its diagnosis is often demanded to post-mortem investigations performed on a forensic setting. Eosinophilic myocarditis (EM) is a rare form of myocarditis that is pathologically characterized by myocardial inflammation with eosinophils, often in association with elevated levels of circulating blood eosinophils. The sudden death of a 19-year-old boy with no past medical history is reported. Diagnosis of fatal acute EM was performed after a comprehensive investigation including an in-depth analysis of anamnestic and circumstantial data, and complete autopsy followed by toxicologic and cardio-pathological investigations. Discussion focuses on the forensic issues related to diagnosis and therapy of this rare form of acute myocarditis. As acute EM may be patchy, extensive myocardial sampling is mandatory in order to recognize the extent and the phase of the disease. An early diagnosis is the basis for a timely therapy, which is the key-point for prevent extensive myocardial damage, allowing a better outcome, especially when EM is acute and necrotizing. However, as demonstrated from the case herein reported, the course of EM is sometimes fulminant and does not allow any therapy nor even clinical diagnosis. Finally, this paper serves as reminder to consider this infrequent disease in differential diagnosis when facing with a sudden death, even in a young subject and in the absence of any prodrome. [ABSTRACT FROM AUTHOR]