Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Dysregulated systemic inflammation is the primary driver of mortality in severe COVID-19 pneumonia. Current guidelines favor a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg·day-1. A comparative RCT with a higher dose and a longer duration of intervention was lacking

White spirit and murder

This case, of legal importance and interest, involved a murder presumably committed by incapacitating the victim with a volatile substance and violent mechanical asphyxiation by suffocation. The court's solution to the case was founded on essential comparative chemico-toxicological analyses and results from non-biological materials obtained during investigations and from biological fluids taken from the body

Determinazione di residui di sparo in ferite d\u2019arma da fuoco putrefatte mediante micro-TC

In cadaveri in avanzato stato di putrefazione l\u2019analisi ispettiva delle ferite d\u2019arma da fuoco pu\uf2 risultare confusa e difficoltosa a causa delle alterazioni indotte da fenomeni autolitici-putrefattivi. Nel presente studio gli Autori propongono l\u2019applicazione della Micro-TC all\u2019identificazione e quantificazione del GSR su ferite d\u2019arma da fuoco sottoposte a putrefazione standardizzata. La micro-TC risulta essere un valido strumento per la diagnosi differenziale tra foro di ingresso e foro di uscita, ma non per la determinazione della distanza di sparo

Alcohol drinking, mean corpuscular volume of erythrocytes, and alcohol metabolic genotypes in drunk drivers

Regular and irregular abuse of alcohol are global health priorities associated with diseases at multiple sites, including cancer. Mechanisms of diseases induced by alcohol are closely related to its metabolism. Among conventional markers of alcohol abuse, the mean corpuscular volume (MCV) of erythrocytes is prognostic of alcohol-related cancer and its predictivity increases when combined with functional polymorphisms of alcohol dehydrogenase (ADH1B [rs1229984] and ADH1C [rs698]) and the mitochondrial aldehyde dehydrogenase (ALDH2 [rs671]). Whether these genetic variants can influence abuse in alcohol drinking and MCV has never been examined in drunk-driving traffic offenders. We examined 149 drunk drivers, diagnosed as alcohol abusers according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition Text Revision (DSM-IV-TR) and enrolled in a probation program, and 257 social drinkers (controls), all Caucasian males. Alcohol intake was assessed according to self-reported drink-units/d and MCV unadjusted and adjusted for age, smoking, and body mass index. Multivariable models were used to compute MCV adjusted means. Genotype analyses were performed by PCR on DNA from blood. The adjusted MCV mean was higher in drunk-driving abusers than in controls (92 vs. 91 fL; P < .0001) and increased with the number of drink-units/d in both abusers and controls (P-trend = .0316 and .0089) already at intermediate quantities (0-1 vs. 2-4 drink-units/d: P = .054 and .024). Carriers of the common ADH1B*1/*1 (rs1229984) genotype were more likely to be drunk-driving abusers (P = .008), reported higher drink-units/d (P = .0126), and had larger MCV (P = .035). The rs698 ADH1C and rs671 ALDH2 polymorphisms were not associated with MCV. ADH1B*1/*1 polymorphism is significantly associated with being a drunk-driving abuser, higher alcohol drinking, and MCV enlargement. This suggests that drunk drivers with augmented MCV modulated by the alcohol metabolic ADH1B*1/*1 genotype may be at higher risk of driving incapability and of alcohol-related cancer. (C) 2012 Elsevier Inc. All rights reserved

Phosphatidylethanol in Blood as a Marker of Chronic Alcohol Use: A Systematic Review and Meta-Analysis

The present paper aims at a systematic review of the current knowledge on phosphatidylethanol (PEth) in blood as a direct marker of chronic alcohol use and abuse. In March 2012, the search through \u201cMeSH\u201d and \u201cfree-text\u201d protocols in the databases Medline/PubMed, SCOPUS, Web of Science, and Ovid/Embase, combining the terms phosphatidylethanol and alcohol, provided 444 records, 58 of which fulfilled the inclusion criteria and were used to summarize the current evidence on the formation, distribution and degradation of PEth in human blood: (1), the presence and distribution of different PEth molecular species (2), the most diffused analytical methods devoted to PEth identification and quantization (3), the clinical efficiency of total PEth quantification as a marker of chronic excessive drinking (4), and the potential utility of this marker for identifying binge drinking behaviors (5). Twelve papers were included in the meta-analysis and the mean (M) and 95% confidence interval (CI) of total PEth concentrations in social drinkers (DAI 64 60 g/die; M = 0.288 \ub5M; CI 0.208\u20130.367 \ub5M) and heavy drinkers (DAI > 60 g/die; M = 3.897 \ub5M; CI 2.404\u20135.391 \ub5M) were calculated. The present analysis demonstrates a good clinical efficiency of PEth for detecting chronic heavy drinking

Non-fatal overdose with U-47700: Identification in biological matrices

BACKGROUND/OBJECTIVE: We report on a case of severe intoxication after insufflation of U-47700, a synthetic opioid that acts as a selective agonist of the \u3bc-opioid receptor, and is several times more potent than morphine. A man in his 30s was found irresponsive in his apartment and was brought to the emergency department of a local hospital. A comatose state and severe respiratory depression were present. Hetero anamnesis revealed that the patient could have taken the substance named "U-47700", bought on the Internet. After supportive care, the patient fully recovered. METHOD: Urine, blood and a white powder found at his home were collected during his hospital stay and sent for testing using liquid chromatography-high resolution mass spectrometry (LC-HRMS) on an Orbitrap instrument. Later, his pubic hair was also collected. A standard comprehensive toxicology screening was performed. RESULTS: U-47700 was identified in all biological samples and in the seized white powder. Using liquid chromatography-high resolution mass spectrometry (LC-HRMS) the presence of U-47700 and its phase I and phase II metabolites in blood, urine and pubic hair was confirmed. U-47700 was determined at 94 ng/mL and 5.2 ng/mL in blood at the admission and the day after, respectively, and 3.02 ng/mg in pubic hair, together with its metabolites. No other opioid nor designer drug could be detected in blood and urine, while in pubic hair Cocaine, Benzoylecgonine, Norcocaine, Mephedrone, Ketamine, Norketamine, 3,4-Methylenedioxymethamphetamine, Tetrahydrocannabinol and Cannabinol were also detected. CONCLUSION: The toxicological findings confirmed the use of U-47700 in the intoxicated patient and also revealed a history of a poly-drug use. The use of LC-HRMS allowed the easy identification of the NPS and its metabolites in fluids and hai

Quantitative profiling of phosphatidylethanol molecular species in human blood by liquid chromatography high resolution mass spectrometry

Phosphatidylethanol (PEth) is a group of aberrant phospholipids formed in cell membranes in the presence of ethanol by the catalytic action of the enzyme phospholipase Don phosphatidylcholine. Recently published literature has demonstrated the existence of several molecular species of PEth in samples drawn from alcohol-dependent subjects. A novel liquid chromatography high-resolution mass spectrometry (LC-HRMS) method coupled with a lipidomic strategy was developed and validated for the quantitative profiling of PEth molecular species in human blood collected from heavy and social drinkers. Chromatography was performed on a C18 column using acetonitrile, 10 mM ammonium acetate, and 2-propanol as mobile phases with a 22-min gradient. HRMS experiments were performed on an LTQ-Orbitrap XL hybrid mass spectrometer equipped with an electrospray ionization source operated in negative ion mode. The theoretical masses of [M-H](-) of PEth species were calculated from the elemental chemical formula by varying the length and unsaturation grade of the fatty acid side chains; identification of PEth species in blood was achieved by searching the accurate masses of the targeted compounds in the acquired full-scan LC-HRMS chromatogram. The chemical structure of tentatively identified PEth species was elucidated through HR multiple mass experiments. The validated LC-HRMS method was selective, as warranted by HRMS at 60,000 resolution and 4 ppm accuracy. Linearity was observed in the 0.001-2.000 mu M range, and limit of detection of 0.0005 mu M and limit of quantitation of 0.001 mu M were obtained for single PEth species. Imprecision and inaccuracy were always lower than 10% and 15%, respectively. The identification capabilities of the method were tested on blood samples collected from heavy drinkers (n = 11), social drinkers (n = 8), and teetotalers (it = 10). The high sensitivity of the method led to the simultaneous identification of 17 different PEth molecular species in blood collected from heavy drinkers, and 2 PEth species (16:0/18:1 and 16:0/18:2) in blood collected from social drinkers. (C) 2011 Elsevier B.V. All rights reserved