In recent years, the consumption of energy drinks by young adults and athletes has risen significantly, but concerns have been raised about the potential health risks associated with excessive consumption. These concerns include cardiovascular problems, nervous system disorders, and the potential for addiction. This review aims to examine the reported effects of acute or chronic abuse of energy drinks on human health. The analysis shows a significant prevalence of adverse effects, particularly on the cardiovascular and neurovegetative systems. In particular, the analysis identified nine cases of cardiac arrest, three of which were fatal. The aetiology of these adverse effects is attributed to the inherent neurostimulant properties of these beverages, of which caffeine is the predominant component. A comparison of documented effects in humans with experimental studies in animal models showed an overlap in results. This review highlights the need for greater rigour in the assessment of sudden cardiac death, particularly in young people, as legal substances such as energy drinks may be involved. We propose stricter limits on the consumption of these beverages than for caffeine, based on the evidence found and the data in the literature. This review also calls for the establishment of regulations governing the consumption of these products in view of their potential impact on human health.

Caffeine is the most widely consumed psychoactive compound worldwide. It is mostly found in coffee, tea, energizing drinks and in some drugs. However, it has become really easy to obtain pure caffeine (powder or tablets) on the Internet markets. Mechanisms of action are dose-dependent. Serious toxicities such as seizure and cardiac arrhythmias, seen with caffeine plasma concentrations of 15 mg/L or higher, have caused poisoning or, rarely, death; otherwise concentrations of 3–6 mg/kg are considered safe. Caffeine concentrations of 80–100 mg/L are considered lethal. The aim of this systematic review, performed following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement for the identification and selection of studies, is to review fatal cases in which caffeine has been recognized as the only cause of death in order to identify potential categories at risk. A total of 92 cases have been identified. These events happened more frequently in infants, psychiatric patients, and athletes. Although caffeine intoxication is relatively uncommon, raising awareness about its lethal consequences could be useful for both clinicians and pathologists to identify possible unrecognized cases and prevent related severe health conditions and deaths.

MicroRNAs (miRNAs) are strongly up‐regulated under pathological stress and in a wide range of diseases. In recent years, miRNAs are under investigation for their potential use as biomarkers in cardiovascular diseases. We investigate whether specific cardio‐miRNAs are overexpressed in heart samples from subjects deceased for acute myocardial infarction (AMI) or sudden cardiac death (SCD), and whether miRNA could help differentiate between them. Forty four cases of death due to cardiovascular disease were selected, respectively, 19 cases categorized as AMI and 25 as SCD. Eighteen cases of traumatic death without pathological cardiac involvement were selected as control. Immunohistochemical investigation was performed for CD15, IL‐15, Cx43, MCP‐1, tryptase, troponin C and troponin I. Reverse transcription and quantitative real‐time PCR were performed for miR‐1, miR‐133, miR‐208 and miR‐499. In AMI group, stronger immunoreaction for the CD15, IL‐15 and MCP‐1 antibodies was detectable compared with SCD and control. Cx43 showed a negative reaction with respect to the other groups. Real‐time PCR results showed a down‐regulation of all miRNAs in the AMI group compared with SCD and control. The selected miRNAs presented high accuracy in discriminating SCD from AMI (miR‐1 and miR‐499) and AMI from control (miR‐208) representing a potential aid for both clinicians and pathologists for differential diagnosis.

This study involves the histological analysis of samples taken during autopsies in cases of COVID-19 related death to evaluate the inflammatory cytokine response and the tissue localization of the virus in various organs. In all the selected cases, SARS-CoV-2 RT-PCR on swabs collected from the upper (nasopharynx and oropharynx) and/or the lower respiratory (trachea and primary bronchi) tracts were positive. Tissue localization of SARS-CoV-2 was detected using antibodies against the nucleoprotein and the spike protein. Overall, we tested the hypothesis that the overexpression of proinflammatory cytokines plays an important role in the development of COVID-19-associated pneumonia by estimating the expression of multiple cytokines (IL-1β, IL-6, IL-10, IL-15, TNF-α, and MCP-1), inflammatory cells (CD4, CD8, CD20, and CD45), and fibrinogen. Immunohistochemical staining showed that endothelial cells expressed IL-1β in lung samples obtained from the COVID-19 group (p < 0.001). Similarly, alveolar capillary endothelial cells showed strong and diffuse immunoreactivity for IL-6 and IL-15 in the COVID-19 group (p < 0.001). TNF-α showed a higher immunoreactivity in the COVID-19 group than in the control group (p < 0.001). CD8 + T cells where more numerous in the lung samples obtained from the COVID-19 group (p < 0.001). Current evidence suggests that a cytokine storm is the major cause of acute respiratory distress syndrome (ARDS) and multiple organ failure and is consistently linked with fatal outcomes.

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Our understanding of its pathobiology has substantially increased. Following TBI, the following occur, edema formation, brain swelling, increased intracranial pressure, changes in cerebral blood flow, hypoxia, neuroinflammation, oxidative stress, excitotoxicity, and apoptosis. Experimental animal models have been developed. However, the difficulty in mimicking human TBI explains why few neuroprotective strategies, drawn up on the basis of experimental studies, have translated into improved therapeutic strategies for TBI patients. In this study, we retrospectively examined brain samples in 145 cases of death after different survival times following TBI, to investigate aquaporin-4 (AQP4) expression and correlation with hypoxia, and neuroinflammation in human TBI. Antibodies anti-glial fibrillary acid protein (GFAP), aquaporin-4 (AQP4), hypoxia induced factor-1α (HIF-1α), macrophage/phagocytic activation (CD68), ionized calcium-binding adapter molecule-1 (IBA-1), and neutrophils (CD15) were used. AQP4 showed a significant, progressive increase between the control group and groups 2 (one-day survival) and 3 (three-day survival). There were further increases in AQP4 immunopositivity in groups 4 (seven-day survival), 5 (14-dayssurvival), and 6 (30-day survival), suggesting an upregulation of AQP4 at 7 to 30 days compared to group 1. GFAP showed its highest expression in non-acute cases at the astrocytic level compared with the acute TBI group. Data emerging from the HIF-1α reaction showed a progressive, significant increase. Immunohistochemistry with IBA-1 revealed activated microglia starting three days after trauma and progressively increasing in the next 15 to 20 days after the initial trauma. CD68 expression demonstrated basal macrophage and phagocytic activation mostly around blood vessels. Starting from one to three days of survival after TBI, an increase in the number of CD68 cells was progressively observed; at 15 and 30 days of survival, CD68 showed the most abundant immunopositivity inside or around the areas of necrosis. These findings need to be developed further to gain insight into the mechanisms through which brain AQP4 is upregulated. This could be of the utmost clinicopathological importance.

Acute traumatic spinal cord injury (SCI) involves primary and secondary injury mechanisms. The primary mechanism is related to the initial traumatic damage caused by the damaging impact and this damage is irreversible. Secondary mechanisms, which begin as early as a few minutes after the initial trauma, include processes such as spinal cord ischemia, cellular excitotoxicity, ionic dysregulation, and free radical-mediated peroxidation. SCI is featured by different forms of injury, investigating the pathology and degree of clinical diagnosis and treatment strategies, the animal models that have allowed us to better understand this entity and, finally, the role of new diagnostic and prognostic tools such as miRNA could improve our ability to manage this pathological entity. Autopsy could benefit from improvements in miRNA research: the specificity and sensitivity of miRNAs could help physicians in determining the cause of death, besides the time of death.