Sepsis and nosocomial infections: The role of medico-legal experts in Italy

Sepsis is a leading cause of morbidity and mortality worldwide. It is defined as the presence of a Systemic Inflammatory Response Syndrome, and it represents a significant burden for the healthcare system. This is particularly true when it is diagnosed in the setting of nosocomial infections, which are usually a matter of concern with regard to medical liability being correlated with increasing economic costs and people’s loss of trust in healthcare. Hence, the Italian governance promotes the clinical risk management with the aim of improving the quality and safety of healthcare services. In this context, the role of medico-legal experts working in a hospital setting is fundamental for performing autopsy to diagnose sepsis and link it with possible nosocomial infections. On the other hand, medico-legal experts are party to the clinical risk management assessment, and deal with malpractice cases and therefore contribute to formulating clinical guidelines and procedures for improving patient safety and healthcare providers’ work practices. Due to this scenario, the authors here discuss the role of medico-legal experts in Italy, focusing on sepsis and nosocomial infections

Sepsis and nosocomial infections: The role of medico-legal experts in Italy

Sepsis is a leading cause of morbidity and mortality worldwide. It is defined as the presence of a Systemic Inflammatory Response Syndrome, and it represents a significant burden for the healthcare system. This is particularly true when it is diagnosed in the setting of nosocomial infections, which are usually a matter of concern with regard to medical liability being correlated with increasing economic costs and people’s loss of trust in healthcare. Hence, the Italian governance promotes the clinical risk management with the aim of improving the quality and safety of healthcare services. In this context, the role of medico-legal experts working in a hospital setting is fundamental for performing autopsy to diagnose sepsis and link it with possible nosocomial infections. On the other hand, medico-legal experts are party to the clinical risk management assessment, and deal with malpractice cases and therefore contribute to formulating clinical guidelines and procedures for improving patient safety and healthcare providers’ work practices. Due to this scenario, the authors here discuss the role of medico-legal experts in Italy, focusing on sepsis and nosocomial infections

A para-religious setting for financial exploitation of the mentally incapacitated: when the habit doesn’t make a monk

Exploitation and circumvention of the mentally incapacitated is a criminal offence listed in the Italian penal code (Penal Code Art. 643). It involves the exploitation and circumvention of people who are fragile and vulnerable owing to their health conditions and/or mental status, and fits into the grey area between such subjects’ freedom to make decisions about their physical conditions and economic assets, and the abuse of their trust perpetrated by third parties for personal gain. The authors describe a case of financial exploitation and circumvention of a married couple that is remarkable in view of both the huge sums extorted from the victims and the duration of the peculiar illicit activities (that lasted more than 10 years). These were perpetrated by a charismatic figure leading a “para-religious” group. He claimed to be a prophet, but his private life was highly questionable. The method of ascertainment used to verify the victims’ mentally incapacitated state is described, analyzed and commented; the diagnosis could not be deferred in view of the characteristics of the prolonged penal offences committe

Occupational asphyxiation by unknown compound(s): Environmental and toxicological approach

During a routine truck-tank washing operation, five healthy workers were found motionless inside an empty tanker. Four of them died inside the tanker while the fifth died the following day in hospital. Since the true nature of the fatal compound(s) were not known, a rigorous environmental and toxicological approach supported by autopsy findings was essential to clarify the cause of death.Environmental results indicated that H2S fumes arising from the liquid sulfur previously shipped were responsible for the serial deaths, also confirmed by a simulation performed on two similar truck-tanks.These environmental findings were supported by toxicological analyses through the measurement of thiosulfate, one of the main H2S metabolites. Abnormal thiosulfate concentrations from 1.1 to 186.2mg/kg were revealed in all post-mortem biological samples (blood, lung, liver, kidney, brain and fat). Finally, the cluster analysis performed on thiosulfate body distribution contributed to establishing the time of death according to the accident scene reconstruction.This report presents valuable findings in correctly identifying the cause of death in gas asphyxiation cases by unknown compound(s). © 2009 Elsevier Ireland Ltd

Incident reporting system in an italian university hospital: A new tool for improving patient safety

Clinical risk management constitutes a central element in the healthcare systems in relation to the reverberation that it establishes, and as regards the optimization of clinical outcomes for the patient. The starting point for a right clinical risk management is represented by the identification of non-conforming results. The aim of the study is to carry out a systematic analysis of all data received in the first three years of adoption of a reporting system, revealing the strengths and weaknesses. The results emerged showed an increasing trend in the number of total records. Notably, 86.0% of the records came from the medical category. Moreover, 41.0% of the records reported the possible preventive measures that could have averted the event and in 30% of the reports are hints to be put in place to avoid the repetition of the events. The second experimental phase is categorizing the events reported. Implementing the reporting system, it would guarantee a virtuous cycle of learning, training and reallocation of resources. By sensitizing health workers to a correct use of the incident reporting system, it could become a virtuous error learning system. All this would lead to a reduction in litigation and an implementation of the therapeutic doctor–patient alliance

Mycobacterium marinum antagonistically induces an autophagic response while repressing the autophagic flux in a TORC1- and ESX-1-dependent manner.

Autophagy is a eukaryotic catabolic process also participating in cell-autonomous defence. Infected host cells generate double-membrane autophagosomes that mature in autolysosomes to engulf, kill and digest cytoplasmic pathogens. However, several bacteria subvert autophagy and benefit from its machinery and functions. Monitoring infection stages by genetics, pharmacology and microscopy, we demonstrate that the ESX-1 secretion system of Mycobacterium marinum, a close relative to M. tuberculosis, upregulates the transcription of autophagy genes, and stimulates autophagosome formation and recruitment to the mycobacteria-containing vacuole (MCV) in the host model organism Dictyostelium. Antagonistically, ESX-1 is also essential to block the autophagic flux and deplete the MCV of proteolytic activity. Activators of the TORC1 complex localize to the MCV in an ESX-1-dependent manner, suggesting an important role in the manipulation of autophagy by mycobacteria. Our findings suggest that the infection by M. marinum activates an autophagic response that is simultaneously repressed and exploited by the bacterium to support its survival inside the MCV

Cellular Reactive Oxygen Species Inhibit MPYS Induction of IFNβ

Many inflammatory diseases, as well as infections, are accompanied by elevation in cellular levels of Reactive Oxygen Species (ROS). Here we report that MPYS, a.k.a. STING, which was recently shown to mediate activation of IFNβ expression during infection, is a ROS sensor. ROS induce intermolecular disulfide bonds formation in MPYS homodimer and inhibit MPYS IFNβ stimulatory activity. Cys-64, -148, -292, -309 and the potential C88xxC91 redox motif in MPYS are indispensable for IFNβ stimulation and IRF3 activation. Thus, our results identify a novel mechanism for ROS regulation of IFNβ stimulation

Potentiation of Epithelial Innate Host Responses by Intercellular Communication

The epithelium efficiently attracts immune cells upon infection despite the low number of pathogenic microbes and moderate levels of secreted chemokines per cell. Here we examined whether horizontal intercellular communication between cells may contribute to a coordinated response of the epithelium. Listeria monocytogenes infection, transfection, and microinjection of individual cells within a polarized intestinal epithelial cell layer were performed and activation was determined at the single cell level by fluorescence microscopy and flow cytometry. Surprisingly, chemokine production after L. monocytogenes infection was primarily observed in non-infected epithelial cells despite invasion-dependent cell activation. Whereas horizontal communication was independent of gap junction formation, cytokine secretion, ion fluxes, or nitric oxide synthesis, NADPH oxidase (Nox) 4-dependent oxygen radical formation was required and sufficient to induce indirect epithelial cell activation. This is the first report to describe epithelial cell-cell communication in response to innate immune activation. Epithelial communication facilitates a coordinated infectious host defence at the very early stage of microbial infection