Abstract
Current clinical diagnosis is typically based on a combination of approaches including clinical examination of the patient, clinical experience, physiologic and/or genetic parameters, high-tech diagnostic medical imaging, and an extended list of laboratory values mostly determined in biofluids such as blood and urine. One could consider this as precision medicine v1.0. However, recent advances in technology and better understanding of molecular mechanisms underlying disease will allow us to better characterize patients in the future. These improvements will enable us to distinguish patients who have similar clinical presentations but different cellular and molecular responses. Treatments will be able to be chosen more “precisely”, resulting in more appropriate therapy, precision medicine v2.0. In this review, we will reflect on the potential added value of recent advances in technology and a better molecular understanding of necrosis and inflammation for improving diagnosis and treatment of critically ill patients. We give a brief overview on the mutual interplay between necrosis and inflammation, which are two crucial detrimental factors in organ and/or systemic dysfunction. One of the challenges for the future will thus be the cellular and molecular profiling of necroinflammation in biofluids. The huge amount of data generated by profiling biomolecules and single cells through, for example, different omic-approaches is needed for data mining methods to allow patient-clustering and identify novel biomarkers. The real-time monitoring of biomarkers will allow continuous (re)evaluation of treatment strategies using machine learning models. Ultimately, we may be able to offer precision therapies specifically designed to target the molecular set-up of an individual patient, as has begun to be done in cancer therapeutics.
Highlights
Patients with similar symptoms can have different diseases, and not all patients with the same disease respond to treatment [1]
Combined intervention strategies controlling infection, inflammation, and necrosis might be the key to effective treatment of multiple organ dysfunction syndrome (MODS)
Advances in precision medicine have been illustrated in oncology, where both diagnosis and treatment are increasingly based on genomic features
Summary
Patients with similar symptoms can have different diseases, and not all patients with the same disease respond to treatment [1]. The experimental and preclinical support is increasing that indicates four not-exclusive key phenomena in the development of MODS: infection, inflammation, parenchymal cell necrosis, and immune cell necrosis (Fig. 2) These major processes result in the circulation of MAMPs, chemo- and cytokines, activated immune cells, and DAMPs, which in an auto-amplifying loop potentially cause distant organ injury. Connecting daily monitoring of an increasing set of circulating biomolecules and immune cells in critically ill patients to data mining will feed machine-learning approaches This form of artificial intelligence allows in a feedback loop continued reevaluation of novel patient stratification strategies and novel biomarkers/therapies targeting necrosis and inflammation (Fig. 3).
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