Gastrointestinal mucositis: a sign of a (systemic) inflammatory response.

PURPOSE OF REVIEW: Gastrointestinal mucositis (GIM) is a significant complication of cancer therapy. Whilst inflammation is a central feature of GIM, studies attempting to mitigate mucosal damage via this mechanism are scarce. This review describes the relation between GIM, local and systemic inflammation, and the microbiome and its metabolites, and explores recent research on therapeutics that target this relationship. RECENT FINDINGS: Recent literature underscores the pivotal role of inflammation in GIM, elucidating its bidirectional relation with disturbance of the gut microbiota composition and intestinal permeability. These events cause a heightened risk of bloodstream infections and lead to systemic inflammation. While studies investigating risk prediction models or therapeutics targeting GIM-related inflammation remain scarce, results have shown promise in finding biomarkers and alleviating GIM and its accompanying clinical symptoms. SUMMARY: The findings underscore the important role of inflammation and the microbiome in GIM. Understanding the inflammatory pathways driving GIM is crucial for developing effective treatments. Further research is needed using genomics, epigenomics, and microbiomics to explore better risk prediction models or therapeutic strategies aimed at mitigating GIM-related inflammation.

NO, way to go: critical amino acids to replenish nitric oxide production in treating mucositis.

PURPOSE OF REVIEW: There is still an unmet need for preventive and treatment strategies for chemotherapy-induced and radiotherapy-induced mucositis and its associated systemic inflammatory response (SIR) in cancer patients. Because of citrulline depletion due to cytotoxic therapy, nitric oxide (NO) production can be reduced, limiting its effect in many physiological processes. Restoring NO production could relieve mucositis severity by supporting host damage control mechanisms. Amino acids glutamine, arginine and citrulline are involved in NO production. This review including recent literature of preclinical and clinical studies will discuss the potential benefits of glutamine, arginine and citrulline on mucositis development with focus on NO production. RECENT FINDINGS: Mucositis severity is more defined by host response to DNA damage than by DMA damage itself. Citrulline depletion because of afunctional enterocytes could be responsible for NO depletion during cytotoxic therapy. Restoring NO production during cytotoxic therapy could have a beneficial effect on mucositis development. Citrulline seems a more promising NO donor than glutamine or arginine during cytotoxic therapy, although clinical studies in mucositis patients are currently lacking. SUMMARY: Glutamine, arginine and citrulline show in-vitro beneficial effects on inflammatory processes involved in mucositis. Translation to the clinic is difficult as demonstrated with use of glutamine and arginine. Citrulline, being the most potent NO donor with excellent oral bio-availability, is very promising as treatment choice for mucositis and its use deserves to be investigated in clinical trials with mucositis patients.

Early differentiation between uncomplicated and complicated Staphylococcus aureus bacteraemia: Potential value and limitations of a clinical risk score.

OBJECTIVE: A cornerstone in the management of Staphylococcus aureus bacteraemia (SAB) is the differentiation between a complicated and an uncomplicated SAB course. The ability to early and accurately identify patients with - and without - complicated bacteraemia may optimise the utility of diagnostics and prevent unnecessary prolonged antibiotic therapy. METHODS: Development and validation of a prediction score in SAB using demographic, clinical, and laboratory data from two independent Dutch cohorts; estimating the risk of complicated disease at the time of the first positive blood culture. Models were developed using logistic regression and evaluated by c-statistics, ie area under the ROC-curve, and negative predictive values (NPV). RESULTS: The development- and validation cohorts included 150 and 183 patients, respectively. The most optimal prediction model included: mean arterial pressure, signs of metastatic infection on physical examination, leucocyte count, urea level and time to positivity of blood cultures (c-statistic 0.82, 95% CI 0.74-0.89). In the validation cohort, the c-statistic of the prediction score was 0,77 (95% CI 0.69-0.84). The NPV for complicated disease for patients with a score of ≤2 was 0.83 (95% CI 0.68-0.92), with a negative likelihood ratio of 0.14 (95% CI 0.06-0.31). CONCLUSION: The early SAB risk score helps to identify patients with high probability of uncomplicated SAB. However, the risk score's lacked absolute discriminative power to guide decisions on the management of all patients with SAB on its own. The heterogenicity of the disease and inconsistency in definitions of complicated SAB are important challenges in the development of clinical rules to guide the management of SAB.