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Immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and psoriasis (Ps), represent autoinflammatory and autoimmune disorders, as well as conditions that have an overlap of both categories. Understanding the underlying pathogeneses, making diagnoses, and choosing individualized treatments remain challenging due to heterogeneous disease phenotypes and the lack of reliable biomarkers that drive the treatment choice. In this review, we provide an overview of the low-molecular-weight metabolites that might be employed as biomarkers for various applications, e.g., early diagnosis, disease activity monitoring, and treatment-response prediction, in RA, PsA, and Ps. The literature was evaluated, and putative biomarkers in different matrices were identified, categorized, and summarized. While some of these candidate biomarkers appeared to be disease-specific, others were shared across multiple IMIDs, indicating common underlying disease mechanisms. However, there is still a long way to go for their application in a routine clinical setting. We propose that studies integrating omics analyses of large patient cohorts from different IMIDs should be performed to further elucidate their pathomechanisms and treatment options. This could lead to the identification and validation of biomarkers that might be applied in the context of precision medicine to improve the clinical outcomes of these IMID patients.
Endocannabinoids (ECs) are potent lipid mediators with high physiological relevance. They are involved in a wide variety of diseases like depression or multiple sclerosis and are closely connected to metabolic parameters in humans. Therefore, their suitability as a biomarker in different (patho-)physiological conditions is discussed intensively and predominantly investigated by analyzing systemic concentrations in easily accessible matrices like blood. Carefully designed pre-analytical sample handling is of major importance for high-quality data, but harmonization is not achieved yet. Whole blood is either processed to serum or plasma before the onset of analytical workflows and while knowledge about pre-analytical challenges in plasma handling is thorough they were not systematically investigated for serum.
Therefore, the ECs AEA and 2-AG, and closely related EC-like substances 1-AG, DHEA, and PEA were examined by LC-MS/MS in serum samples of nine healthy volunteers employing different pre-analytical sample handling protocols, including prolonged coagulation, and storage after centrifugation at room temperature (RT) or on ice. Furthermore, all analytes were also assessed in plasma samples obtained from the same individuals at the same time points to investigate the comparability between those two blood-based matrices regarding obtained concentrations and their 2-AG/1-AG ratio.
This study shows that ECs and EC-like substances in serum samples were significantly higher than in plasma and are especially prone to ex vivo changes during initial and prolonged storage for coagulation at RT. Storage on ice after centrifugation is less critical. However, storage at RT further increases 1-AG and 2-AG concentrations, while also lowering the already reduced 2-AG/1-AG ratio due to isomerization. Thus, avoidance of prolonged processing at RT can increase data quality if serum as the matrix of choice is unavoidable. However, serum preparation in itself is expected to initiate changes of physiological concentrations as standard precautionary measures like fast and cooled processing can only be utilized by using plasma, which should be the preferred matrix for analyses of ECs and EC-like substances.
Objective: Skin and soft tissue infections (SSTI) are a commonly known entity of diseases associated with difficult treatment procedures. The current gold standard when there is a rapidly progressing infection of soft tissues with a risk of sepsis is radical surgical debridement accompanied by systemic antibiotic therapy. In clinical settings, local antibiotics alone or formulated within carrier material are commonly used alongside this therapy regimen. One possibility of local antibiotic application is the fixation of colistin with fibrin glue spray. It is not yet sufficiently researched how the local antibiotic concentrations remain as high as possible over time.
Methods: We conducted an animal study including 29 male Wistar rats inducing sterile back sores reaching the muscle fascia. We sprayed only colistin, simultaneously or consecutively, with fibrin glue in different groups in order to measure the tissue concentration of the antibiotic applied locally.
Results: After liquid chromatography and quadrupole mass spectrometry analysis, it could be demonstrated that in comparison to the colistin group, tissue concentrations of colistin stayed significantly higher in the wound tissue when it was fixed with fibrin glue. This was observed in both groups, the simultaneous as well as in the consecutively fibrin glue sprayed groups after colistin application.
Conclusion: The fixation of colistin with the fibrin-glue-spray technique as a carrier for local antibiotic therapy is an easy and inexpensive method and shows promising potential for the treatment of SSTI.