Paving the way for precision medicine v2.0 in intensive care by profiling necroinflammation in biofluids

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.

“Point of no return” in unilateral renal ischemia reperfusion injury in mice

“…The results of this study suggest cell death inhibitors or suppressors of inflammation to be tested in future studies. Thereby this study serves as early step to help pave the way for a delayed, phase dependent and precise therapy of ATN to avoid transition to CKD [50].…”

The Role of Adipokines as Circulating Biomarkers in Critical Illness and Sepsis

“…In the last decade, many different treatment approaches were approved based on specific genetic characteristics such as anti-EGFR directed therapies in patients with RAS wild-type colorectal cancer [7]. Thus, providing individualized or personalized medicine requires the availability of specific “biomarkers” that allow stratification of patients into different subgroups [8]. The National Institutes of Health (NIH) define a biomarker as “any substance, structure, or process that can be measured in the body or its products and influence or predict the incidence or outcome of disease” or, more broadly, as “almost any measurement reflecting an interaction between a biological system and a potential hazard, which may be chemical, physical, or biological.…”

Dynamical modeling of pro- and anti-inflammatory cytokines in the early stage of septic shock

“…Further consideration of the probesets narrowed down the number of potential cytokines for modelling to 14, each of which has data available for both receptors and cytokine (about 30 probesets) : IL1A, IL1B, IL2, IL3, IL4, IL6, IL10, IL11, IL12A, IL13, IL16, IL18, IL24 and IL27. Of these, IL1, IL4, IL6, IL10, IL18 have been strongly associated with sepsis [7,[34][35][36][37][38][39][40], with 1L1, IL6 and IL18 being proinflammatory and IL4 and IL10 anti-inflammatory. From this set of 5 cytokines, IL18/IL10 was identified as the optimal pair for modelling.…”