Ischemia–reperfusion injury is a major cause of acute kidney injury. Many cytokines are involved in the pathogenesis of renal ischemia–reperfusion injury. IL24 is a member of the IL10 family and has ...gained importance because of its apoptosis‐inducing effects in tumor disease besides its immunoregulative function. Littles is known about the role of IL24 in kidney disease. Using a mouse model, we found that IL24 is upregulated in the kidney after renal ischemia–reperfusion injury and that tubular epithelial cells and infiltrating inflammatory cells are the source of IL24. Mice lacking IL24 are protected from renal injury and inflammation. Cell culture studies showed that IL24 induces apoptosis in renal tubular epithelial cells, which is accompanied by an increased endoplasmatic reticulum stress response. Moreover, IL24 induces robust expression of endogenous IL24 in tubular cells, fostering ER‐stress and apoptosis. In kidney transplant recipients with delayed graft function and patients at high risk to develop acute kidney injury after cardiac surgery IL24 is upregulated in the kidney and serum. Taken together, IL24 can serve as a biomarker, plays an important mechanistic role involving both extracellular and intracellular targets, and is a promising therapeutic target in patients at risk of or with ischemia‐induced acute kidney injury.
In vitro and in vivo study shows that, during kidney ischemia / reperfusion injury, interleukin 24 induces apoptosis and endoplasmic reticulum stress in renal tubular epithelial cells, leading to acute kidney injury.
Sepsis and septic shock are a major public health concern and are still associated with high rates of morbidity and mortality. Whilst there is growing understanding of different phenotypes and ...endotypes of sepsis, all too often treatment strategies still only employ a “one-size-fits-all” approach. Biomarkers offer a unique opportunity to close this gap to more precise treatment approaches by providing insight into clinically hidden, yet complex, pathophysiology, or by individualizing treatment pathways. Predicting and evaluating systemic inflammation, sepsis or septic shock are essential to improve outcomes for these patients. Besides opportunities to improve patient care, employing biomarkers offers a unique opportunity to improve clinical research in patients with sepsis. The high rate of negative clinical trials in this field may partly be explained by a high degree of heterogeneity in patient cohorts and a lack of understanding of specific endotypes or phenotypes. Moving forward, biomarkers can support the selection of more homogeneous cohorts, thereby potentially improving study conditions of clinical trials. This may finally pave the way to a precision medicine approach to sepsis, septic shock and complication of sepsis in the future.
Individualized medicine uses data on biological characteristics of individual patients in order to tailor treatment planning to their unique constitution. With respect to the practice of ...anesthesiology and intensive care medicine, it bears the potential to systematize the often complex medical care of critically ill patients and to improve outcomes.
The aim of this narrative review is to provide an overview of the possible applications of the principles of individualized medicine in anesthesiology and intensive care medicine.
Based on a search in MEDLINE, CENTRAL and Google Scholar, the results of previous studies and systematic reviews are narratively synthesized and the implications for the scientific and clinical practice are presented.
There are possibilities for individualization and an increase in precision of patient care in most if not all problems in anesthesiology and symptoms in intensive medical care. Even now, all practicing physicians can initiate measures to individualize treatment at different timepoints throughout the course of treatment. Individualized medicine can supplement and be integrated into protocols. Plans for future applications of individualized medicine interventions should consider the feasibility in a real-world setting. Clinical studies should contain process evaluations in order to create ideal preconditions for a successful implementation. Quality management, audits and feedback should become a standard procedure to ensure sustainability. In the long run, individualization of care, especially in the critically ill, should be enshrined in guidelines and become an integral part of clinical practice.
Abstract
Rationale
Steroid profiles in combination with a corticotropin stimulation test provide information about steroidogenesis and its functional reserves in critically ill patients.
Objectives
...We investigated whether steroid profiles before and after corticotropin stimulation can predict the risk of in-hospital death in sepsis.
Methods
An exploratory data analysis of a double blind, randomized trial in sepsis (HYPRESS HYdrocortisone for PRevention of Septic Shock) was performed. The trial included adult patients with sepsis who were not in shock and were randomly assigned to placebo or hydrocortisone treatment. Corticotropin tests were performed in patients prior to randomization and in healthy subjects. Cortisol and precursors of glucocorticoids (17-OH-progesterone, 11-desoxycortisol) and mineralocorticoids (11-desoxycorticosterone, corticosterone) were analyzed using the multi-analyte stable isotope dilution method (LC–MS/MS). Measurement results from healthy subjects were used to determine reference ranges, and those from placebo patients to predict in-hospital mortality.
Measurements and main results
Corticotropin tests from 180 patients and 20 volunteers were included. Compared to healthy subjects, patients with sepsis had elevated levels of 11-desoxycorticosterone and 11-desoxycortisol, consistent with activation of both glucocorticoid and mineralocorticoid pathways. After stimulation with corticotropin, the cortisol response was subnormal in 12% and the corticosterone response in 50% of sepsis patients. In placebo patients (
n
= 90), a corticotropin-stimulated cortisol-to-corticosterone ratio > 32.2 predicted in-hospital mortality (AUC 0.8 CI 0.70–0.88; sensitivity 83%; and specificity 78%). This ratio also predicted risk of shock development and 90-day mortality.
Conclusions
In this exploratory analysis, we found that in sepsis mineralocorticoid steroidogenesis was more frequently impaired than glucocorticoid steroidogenesis. The corticotropin-stimulated cortisol-to-corticosterone ratio predicts the risk of in-hospital death.
Trial registration
Clinical trial registered with
www.clinicaltrials.gov
Identifier: NCT00670254. Registered 1 May 2008,
https://clinicaltrials.gov/ct2/show/NCT00670254
.
Abstract Purpose There is evidence that lower activity of the RAF/MEK/ERK network is associated with positive outcomes in mild and moderate courses of COVID-19. The effect of this cascade in COVID-19 ...sepsis is still undetermined. Therefore, we tested the hypothesis that activity of the RAF/MEK/ERK network in COVID-19-induced sepsis is associated with an impact on 30-day survival. Methods We used biomaterial from 81 prospectively recruited patients from the multicentric CovidDataNet.NRW-study cohort (German clinical trial registry: DRKS00026184) with their collected medical history, vital signs, laboratory parameters, microbiological findings and patient outcome. ERK activity was measured by evaluating ERK phosphorylation using a Proximity Ligation Assay. Results An increased ERK activity at 4 days after diagnosis of COVID-19-induced sepsis was associated with a more than threefold increased chance of survival in an adjusted Cox regression model. ERK activity was independent of other confounders such as Charlson Comorbidity Index or SOFA score (HR 0.28, 95% CI 0.10–0.84, p = 0.02). Conclusion High activity of the RAF/MEK/ERK network during the course of COVID-19 sepsis is a protective factor and may indicate recovery of the immune system. Further studies are needed to confirm these results.
Zusammenfassung
Die Nierenersatztherapie ist neben der Beatmung eines der wichtigsten und am häufigsten angewendeten Organersatzverfahren in der täglichen Praxis in der Intensivmedizin. Im Gegensatz ...zur Beatmungstherapie sind Qualitätsstandards für die Nierenersatztherapie weniger gut definiert und bekannt. In diesem Positionspapier der Deutschen Interdisziplinären Vereinigung für Intensivmedizin (DIVI) beschreiben wir Qualitätsstandards zur Nierenersatztherapie mit dem Ziel die Behandlungsqualität der Patienten mit einem schweren akuten Nierenversagen zu verbessern.
Die Nierenersatztherapie ist neben der Beatmung eines der wichtigsten und am häufigsten angewendeten Organersatzverfahren in der täglichen Praxis in der Intensivmedizin. Im Gegensatz zur ...Beatmungstherapie sind Qualitätsstandards für die Nierenersatztherapie weniger gut definiert und bekannt. In diesem Positionspapier der Deutschen Interdisziplinären Vereinigung für Intensivmedizin (DIVI) beschreiben wir Qualitätsstandards zur Nierenersatztherapie mit dem Ziel die Behandlungsqualität der Patienten mit einem schweren akuten Nierenversagen zu verbessern.
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