Hair analysis to discriminate voluntary doping vs inadvertent ingestion of the aromatase inhibitor letrozole.

Letrozole is an aromatase inhibitor, used to treat postmenopausal women with hormone receptor-positive or unknown advanced breast cancer. It is prohibited in sport because it is used together with androgen anabolizing steroids to avoid their adverse effects. In the case of an adverse analytical finding, it may be important to distinguish between repetitive use due to voluntary administration and occasional use, possibly due to involuntary intake. With the objective to identify the dose capable of producing a positive hair test, and to apply these results to the scenarios of inadvertent letrozole ingestion by an athlete, this study investigates the urinary excretion and incorporation into hair of single doses of letrozole. Seven subjects were recruited for an excretion study of letrozole and its metabolite bis(4-cyanophenyl) methanol (M1) in urine, after the consumption of 0.62 mg, 1.25 mg, and 2.5 mg of letrozole, and to investigate the incorporation in hair after ingestion of 0.62 mg and 2.5 mg of letrozole. Urine and hair samples were also obtained from two women in chronic therapy. Urinary concentrations of letrozole and its metabolite M1 were lower in subjects administered once with 0.62 mg, 1.25 mg, or 2.5 mg letrozole than in women in regular therapy with 2.5 mg/day. In hair collected after a single dosage, concentrations of 16-60 pg/mg were detected while in women in chronic therapy concentrations were higher than 160 pg/mg all along the hair shaft. Hair analysis turned to be a promising possibility for the discrimination of letrozole repetitive use vs occasional/inadvertent administration.

Planking or the "Lying-Down Game:" Two Case Reports.

BACKGROUND: The monitoring and management of risks regarding children and young people admitted to the emergency department as a result of dangerous behaviors distributed via the Internet should be based on clinical reasoning and knowledge about these social media-related phenomena. Here we examine 2 cases of teenagers who reported severe injuries while performing the "planking" craze, a challenge that consists in lying face-down stiffly like a board on any kind of surface. OBJECTIVE: Our objective is to examine and describe the Internet craze called planking, also known as the "lying-down game," through 2 case reports from our experience, enriching this study with information gained through discussions with secondary school teenagers. METHODS: Details of the 2 case reports were taken from electronic medical records giving information on care support processes, care management, and the costs of traumatic episodes. Demographic data, hemoglobin and serum lactate values, and Injury Severity Scores were evaluated. The study took place in secondary schools of our city from 2013 to 2014 during medical education courses, with the aim of analyzing the influence of social media on teenagers' activities and behaviors. RESULTS: Both patients suffered multiple trauma injuries and needed high-level health assistance. The first patient underwent a splenectomy and the second one a nephrectomy; both of them required a long hospital stay (14 and 20 days, respectively), and the costs for their management have been estimated at US $27,000 and US $37,000, respectively. Their decision to perform the planking in dangerous locations was due to their ambition to gain peers' acclaim through shared videos and pictures. CONCLUSIONS: Reporting and understanding these cases may potentially help prevent future events occurring in similar circumstances: the scientific community cannot leave this problem unaddressed. There is also a role of education resources for health care professionals; for this, we must identify and follow up strange or misleading information found on websites. A key element of this research study was to report physicians' misperceptions concerning planking and, with these cases used for teaching purposes, improve knowledge of the clinical and forensic aspects of this emerging problem.

Fatal asthma; is it still an epidemic?

BACKGROUND: Asthma mortality has declined since the 1980s. Nevertheless the World Health Organization (WHO) identified asthma as responsible for 225.000 deaths worldwide in 2005, and 430.000 fatal cases are expected by 2030. Some unexpected and concentrated fatal asthma events all occurred between 2013 and 2015 in Veneto, a North Eastern region of Italy, which prompted a more in-depth investigation of characteristics and risk factors. METHODS: A web search including key words related to fatal asthma in Italy between 2013 and 2015 has been performed. Concerning the cases that occurred in Veneto, subjects' clinical records have been evaluated and details about concomitant weather conditions, pollutants and pollen count have been collected. RESULTS: Twenty-three cases of asthma deaths were found in Italy; 16 of them (69%) occurred in the Veneto Region. A prevalence of male and young age was observed. Most of patients were atopic, died in the night-time hours and during the weekends. The possible risk factors identified were the sensitization to alternaria, previous near fatal asthma attacks and the incorrect treatment of the disease. Weather condition did not appear to be related to the fatal exacerbations, whereas among the pollutants only ozone was detected over the accepted limits. Smoking habits, possible drug abuse and concomitant complementary therapies might be regarded as further risk factors. DISCUSSION: Although not free from potential biases, our web search and further investigations highlight an increasing asthma mortality trend, similarly to what other observatories report. The analysis of available clinical data suggests that the lack of treatment more than a severe asthma phenotype characterizes the fatal events. CONCLUSIONS: Asthma mortality still represents a critical issue in the management of the disease, particularly in youngsters. Once more the inadequate treatment and the lack of adherence seem to be not only related to the uncontrolled asthma but also to asthma mortality.

Anabolic androgenic steroids abuse and cardiac death in athletes: morphological and toxicological findings in four fatal cases.

Anabolic androgenic steroids (AAS) are the main class of doping agents and their consumption produces adverse effects involving several organs and systems. Three cases of sudden cardiac death (SCD) and one of death due to congestive heart failure of previously healthy athletes who were AAS users are herein reported. Concentric cardiac hypertrophy with focal fibrosis (one case), dilated cardiomyopathy with patchy myocyte death (two cases) and eosinophilic myocarditis (one case) were observed and most probably relate to the final event. Molecular investigation for viral genomes was positive in one case (Ebstein virus). Our data confirm previous findings, showing that the most typical cardiac abnormality in AAS abusers is left ventricular hypertrophy, associated with fibrosis and myocytolysis. An exceptional cardiovascular substrate was represented by the case with drug induced eosinophilic myocarditis. These features are at risk of ventricular arrhythmias as well as congestive heart failure. The cause-effect relationship between AAS abuse and cardiac death can be established only by a rigorous methodology with the use of standardized protocols, including precise morphological studies of all target organs to search for chronic toxic effects. Laboratory investigations should focus on AAS searching on a wide range of biological matrices to demonstrate type, magnitude and time of exposure.

Retroperitoneal fibrosis after chemotherapy.

We report the case of a patient with a non-Hodgkin lymphoma, who after a standard chemotherapy protocol, developed retroperitoneal fibrosis (RPF) in the absence of radiotherapy or other known causes. The final diagnosis was reached with the microscopic examination of tissue obtained by fine-needle aspiration and true-cut biopsy of the retroperitoneal mass. RPF can be related to chemotherapy alone.