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Background. Sepsis is among the leading causes of death worldwide and is the focus of a great deal of attention from policymakers and caregivers. However, sepsis poses significant challenges from a clinical point of view regarding its early detection and the best organization of sepsis care. Furthermore, we do not yet have reliable tools for measuring the incidence of sepsis. Methods based on analyses of insurance claims are unreliable, and postmortem diagnosis is still challenging since autopsy findings are often nonspecific. Aim. The objective of this review is to assess the state of our knowledge of the molecular and biohumoral mechanisms of sepsis and to correlate them with our postmortem diagnosis ability. Conclusion. The diagnosis of sepsis-related deaths is an illustrative example of the reciprocal value of autopsy both for clinicians and for pathologists. A complete methodological approach, integrating clinical data by means of autopsy and histological and laboratory findings aiming to identify and demonstrate the host response to infectious insults, is mandatory to illuminate the exact cause of death. This would help clinicians to compare pre- and postmortem findings and to reliably measure the incidence of sepsis.

Background. Myocardial depression in sepsis is common, and it is associated with higher mortality. In recent years, the hypothesis that the myocardial dysfunction during sepsis could be mediated by ischemia related to decreased coronary blood flow waned and a complex mechanism was invoked to explain cardiac dysfunction in sepsis. Oxidative stress unbalance is thought to play a critical role in the pathogenesis of cardiac impairment in septic patients. Aim. In this paper, we review the current literature regarding the pathophysiology of cardiac dysfunction in sepsis, focusing on the possible role of oxidative-nitrosative stress unbalance and mitochondria dysfunction. We discuss these mechanisms within the broad scenario of cardiac involvement in sepsis. Conclusions. Findings from the current literature broaden our understanding of the role of oxidative and nitrosative stress unbalance in the pathophysiology of cardiac dysfunction in sepsis, thus contributing to the establishment of a relationship between these settings and the occurrence of oxidative stress. The complex pathogenesis of septic cardiac failure may explain why, despite the therapeutic strategies, sepsis remains a big clinical challenge for effectively managing the disease to minimize mortality, leading to consideration of the potential therapeutic effects of antioxidant agents.

Oxidative stress in heart failure or during ischemia/reperfusion occurs as a result of the excessive generation or accumulation of free radicals or their oxidation products. Free radicals formed during oxidative stress can initiate lipid peroxidation, oxidize proteins to inactive states and cause DNA strand breaks. Oxidative stress is a condition in which oxidant metabolites exert toxic effects because of their increased production or an altered cellular mechanism of protection. In the early phase of acute heart ischemia cytokines have the feature to be functional pleiotropy and redundancy, moreover, several cytokines exert similar and overlapping actions on the same cell type and one cytokine shows a wide range of biological effects on various cell types. Activation of cytokine cascades in the infarcted myocardium was established in numerous studies. In experimental models of myocardial infarction, induction and release of the pro-inflammatory cytokines like TNF-α (Tumor Necrosis Factor α), IL-1β (Interleukin- 1β) and IL-6 (Interleukin-6) and chemokines are steadily described. The current review examines the role of oxidative stress and pro-inflammatory cytokines response following acute myocardial infarction and explores the inflammatory mechanisms of cardiac injury.

In forensic practice, it is required to distinguish between suicidal or accidental hanging and simulated hanging. Conventional macroscopic and histological findings may be unreliable; vital signs are often absent, and they can be produced postmortem. The application of immunohistochemical techniques opened up a new field of investigation in the issue of ligature marks. We investigated the immunohistochemical expression of a panel of cytokines and inflammatory cells in skin specimens in autopsy cases of death due to hanging, to discuss their significance in assessing whether hanging mark and signs occurred before or after the death of the victim. We selected 21 cases in which broad, soft and yielding materials were used and 28 cases in which materials used for hanging were hard. The control group included the following 21 cases: 14 cases of sudden cardiac death and 7 cases of postmortem hanging (suspension) of bodies (drug overdose or suffocation as cause of death in all the cases). An immunohistochemical investigation of skin samples was performed utilizing antibodies anti-tryptase, fibronectin, TNFα, IL-6, IL-8, IL-10, MCP-1, IL-15, IL-1ß, CD45, CD4, CD3, CD8, CD68, CD20, CD15. We conclude that tryptase, IL-15, and CD15 appear to be reliable parameters in the determination of ligature marks’ vitality with the accuracy needed for forensic purposes. This fact especially applies to soft marks which are particularly difficult to evaluate on the basis of gross examination and of conventional histological studies.