The biomedical company of the University of Valencia Science Park (PCUV) contributes to studies focused on the identification of specific phenotypes in patients, the mechanisms that trigger sepsis and the validation of biomarkers. September 13 is World Sepsis Day, a serious and life-threatening condition caused by an abnormal response to an infection
The INCLIVA Health Research Institute of the University Clinical Hospital of Valencia is developing several lines of research to improve the knowledge of sepsis, a condition caused by an abnormal response to an infection that produces altered physiological responses, which can lead to organ dysfunction and, in some cases, death.
Sepsis is a complex and heterogeneous severe systemic condition, so there is currently great interest in identifying specific patient phenotypes in order to apply a precision medicine approach and thus increase the success of therapies.
INCLIVA's Epigenomics and Translational Epigenetics Research Group, coordinated by José Luis García Giménez, also a professor in the Department of Physiology at the University of Valencia (UV) and CEO of EpiDisease SL, a company housed in the University of Valencia Science Park, is using massive microRNA sequencing techniques and DNA methylation analysis to identify specific phenotypes in sepsis patients with the aim of understanding inflammation and immunosuppression phenomena, is using massive microRNA sequencing techniques and DNA methylation analysis to identify specific phenotypes in sepsis patients with the aim of understanding the phenomena of inflammation and immunosuppression in them.
On the other hand, the group is investigating the mechanisms of cell death mediated by circulating histones (proteins that play a crucial role in the organization and regulation of DNA, but which outside the nucleus turn out to be harmful mediators for cells) and, in this way, understand how these contribute to the different processes of tissue damage, immunodysregulation, alteration of endothelial function (fundamental for maintaining vascular health and regulating various processes in the organism) and coagulopathy phenomena.
In addition, he is also working, together with the UV and the biomedical company EpiDisease in the project 'Identification and validation of biomarkers using omics and Artificial Intelligence for early diagnosis and improvement of clinical management of sepsis' in order to develop different methods based on mass spectrometry to quantify different biomarkers related to inflammation, oxidative stress and immunosuppression in sepsis patients.
EpiDisease SL is currently validating the technology in a multicenter, international clinical trial involving several centers in Spain and Italy, including INCLIVA and the University Clinical Hospital of Valencia. The trial will rigorously evaluate the efficacy and reliability of the HistSHOCK DIV tool in the intensive care clinical setting. In addition, the project includes the preparation of the technical dossier for submission to the European Union regulatory authorities
Another of the projects in which the research group participates is the clinical validation of the HistSHOCK kit, an innovative In Vitro Diagnostic (IVD) tool being developed by EpiDisease SL, based on a patent of INCLIVA, CIBER and UV, designed to improve early diagnosis, treatment strategies and prognosis of sepsis.
It is a method for the simultaneous and automated analysis of circulating histones (H3 and H2B) and protein C in plasma samples from sepsis patients that have been validated as biomarkers to diagnose, stratify by severity and monitor sepsis, predict progression to septic shock and contribute to the identification of those patients at high risk of developing Disseminated Intravascular Coagulation (DIC). As HistSHOCK is a dynamic test, the effects of interventions on the course of the disease can be effectively monitored, allowing them to be tailored to each patient's response.
Studies to date have already demonstrated their ability to significantly reduce the number of false positive diagnoses and differentiate sepsis from other non-infectious hyperinflammatory processes in the Intensive Care Unit with similar symptoms. Recently, the potential use of these technologies has also been demonstrated to identify, just after admission, patients who will require life-sustaining therapies (i.e. mechanical ventilation and renal replacement therapy), thus helping to anticipate therapeutic interventions in critical cases.
EpiDisease SL is currently validating the technology in a multicenter, international clinical trial involving several centers in Spain and Italy, including INCLIVA and the University Clinical Hospital of Valencia. The trial will rigorously evaluate the efficacy and reliability of the HistSHOCK DIV tool in the intensive care clinical setting. In addition, the project includes the preparation of the technical dossier for submission to the European Union regulatory authorities, with a view to its approval as an in vitro diagnostic product with CE-IVD marking and its subsequent commercial launch.
Sepsis affects some 49 million patients and is one of the leading causes of death in hospitals worldwide (in-hospital mortality due to sepsis is more than 10%), with 11 million deaths per year
The target group for HistSHOCK is patients with suspected sepsis (SoS cases). It is estimated that there are between 240 and 685 million SoS cases worldwide. The commercialization plan focuses on Spain, France, Germany, Italy, UK, USA, China and Japan, with a total addressable market of 149 million SoS each year.
The INCLIVA Biobank is participating in all research projects, including the HistSHOCK clinical validation trial. The new Mass Spectrometry Unit, which is in charge of measuring the levels of circulating histones and protein C in the collected samples, is also actively participating. This research is funded by FIS projects of the Carlos III Health Institute and the Ministry of Science, Innovation and Universities and by a public-private collaboration project funded by the State Research Agency in the program of Aid for Public-Private Collaboration Projects of the State Plan for Scientific, Technical and Innovation Research 2021-2023 in the framework of the Recovery, Transformation and Resilience Plan. The HistShock technology validation trial is funded by the Seal of Excellence Projects program of the Horizon Europe Program, and financed by the Center for the Development of Industrial Technology (CDTI) of the Ministry of Science and Innovation and NextGeneration EU funds.
World Sepsis Day
Today is World Sepsis Day, a serious condition affecting some 49 million patients and one of the leading causes of death in hospitals worldwide (in-hospital mortality due to sepsis is over 10%), with 11 million deaths annually. In addition, the number of sepsis cases is increasing every year due to an increasingly aging world population suffering from more chronic diseases.
Sepsis occurs unpredictably and can progress rapidly. In severe cases, one or more organ systems fail. In the worst cases, blood pressure drops, the heart weakens and the patient spirals into septic shock. Once this occurs, multiple organs (lungs, kidneys, liver) may fail rapidly and the patient may die.
In addition, sepsis is one of the main causes of hospital readmission (almost 74% of readmissions per year). The annual cost due to sepsis and its complications exceeds 75 billion euros.
Currently there is no specific test for sepsis, and health care professionals have to identify sepsis by considering several variables between the patient's symptoms and test results. For example, blood count, lactate, C-reactive protein, blood cultures and prothrombin time tests may indicate the presence of an infection by highlighting specific symptoms, but not by identifying the infection itself.