The aim of this study was to evaluate whether Interleukin-6 (IL-6) could be a faster indicator of treatment success in adults with severe sepsis and septic shock compared to procalcitonin (PCT) and C-reactive protein (CRP). Data from adult patients with severe sepsis and septic shock managed at the medical intensive care unit (ICU) of the University Hospital Leipzig between September 2009 and January 2012 were analyzed retrospectively. Values for CRP, PCT and IL-6 on admission as well as after 24 and 48–72 h were collected. Antibiotic therapy was defined as clinically successful if the patient survived ICU stay. A total of 328 patients with severe sepsis and septic shock with adequate data quality were included. After 48–72 h, the median IL-6 was significantly lower in survivors than in non-survivors (114.2 pg/ml vs. 746.6 pg/ml; p < 0.001), while there was no significant difference for PCT (5.6 vs. 4.9 ng/ml; p = 0.586) and CRP (158.5 mg/l vs. 172.4 mg/l; p = 0.988). The results of this study suggest that IL-6 is better than PCT and CRP in predicting the treatment success in predominantly non-surgical sepsis in the first 48–72 h.

Timely diagnosis is crucial for sepsis treatment. Current machine learning (ML) models suffer from high complexity and limited applicability. We therefore created an ML model using only complete blood count (CBC) diagnostics. We collected non-intensive care unit (non-ICU) data from a German tertiary care centre (January 2014 to December 2021). Using patient age, sex, and CBC parameters (haemoglobin, platelets, mean corpuscular volume, white and red blood cells), we trained a boosted random forest, which predicts sepsis with ICU admission. Two external validations were conducted using data from another German tertiary care centre and the Medical Information Mart for Intensive Care IV database (MIMIC-IV). Using the subset of laboratory orders also including procalcitonin (PCT), an analogous model was trained with PCT as an additional feature. After exclusion, 1 381 358 laboratory requests (2016 from sepsis cases) were available. The CBC model shows an area under the receiver operating characteristic (AUROC) of 0.872 (95% CI, 0.857–0.887). External validations show AUROCs of 0.805 (95% CI, 0.787–0.824) for University Medicine Greifswald and 0.845 (95% CI, 0.837–0.852) for MIMIC-IV. The model including PCT revealed a significantly higher AUROC (0.857; 95% CI, 0.836–0.877) than PCT alone (0.790; 95% CI, 0.759–0.821; P < 0.001). Our results demonstrate that routine CBC results could significantly improve diagnosis of sepsis when combined with ML. The CBC model can facilitate early sepsis prediction in non-ICU patients with high robustness in external validations. Its implementation in clinical decision support systems has strong potential to provide an essential time advantage and increase patient safety.

The liver plays a key role in amino acid metabolism. In former studies, a ratio between branched-chain and aromatic amino acids (Fischer’s ratio) revealed associations with hepatic encephalopathy. Furthermore, low concentrations of branched-chain amino acids were linked to sarcopenia in literature. Encephalopathy and sarcopenia are known to dramatically worsen the prognosis. Aim of this study was to investigate a complex panel of plasma amino acids in the context of mortality in patients with end-stage liver disease. 166 patients evaluated for orthotopic liver transplantation were included. 19 amino acids were measured from citrated plasma samples using mass spectrometry. We performed survival analysis for plasma amino acid constellations and examined the relationship to established mortality predictors. 33/166 (19.9%) patients died during follow-up. Lower values of valine (p<0.001), Fischer’s ratio (p<0.001) and valine to phenylalanine ratio (p<0.001) and higher values of phenylalanine (p<0.05) and tyrosine (p<0.05) were significantly associated with mortality. When divided in three groups, the tertiles discriminated cumulative survival for valine (p = 0.016), phenylalanine (p = 0.024) and in particular for valine to phenylalanine ratio (p = 0.003) and Fischer’s ratio (p = 0.005). Parameters were also significantly correlated with MELD and MELD-Na score. Amino acids in plasma are valuable biomarkers to determine increased risk of mortality in patients with end-stage liver disease. In particular, valine concentrations and constellations composed of branched-chain and aromatic amino acids were strongly associated with prognosis. Due to their pathophysiological importance, the identified amino acids could be used to examine individual dietary recommendations to serve as potential therapeutic targets.

Raman spectroscopy has shown to be a promising method for the examination of biomedical samples. However, until now, its efficacy has not been established in clinical diagnostics. In this study, Raman spectroscopy’s potential application in medical laboratories is evaluated for a large variety (38) of biomarkers. Given 234 serum samples from a cohort of patients with different stages of liver disease, we performed Raman spectroscopy at 780nm excitation wavelength. The Raman spectra were analyzed in combination with the results of routine diagnostics using specifically developed complex mathematical algorithms, including fluorescence filtering, frequency subset selection and several overfitting circumventing strategies, such as independent validation. With the results of this cohort, which were validated in 328 independent samples, a significant proof-of-concept study was completed. This study highlights the need to prevent overfitting and to use independent data for validation. The results reveal that Raman spectroscopy has high potential for use in medical laboratory diagnostics to simultaneously quantify multiple biomarkers.

The association of circulating sphingosine-1-phosphate (S1P), a bioactive lipid involved in various cellular processes, and related metabolites such as sphinganine-1-phosphate (SA1P) and sphingosine (SPH) with mortality in patients with end-stage liver disease is investigated in the presented study. S1P as a bioactive lipid mediator, is involved in several cellular processes, however, in end-stage liver disease its role is not understood. The study cohort consisted of 95 patients with end-stage liver disease and available information on one-year outcome. The median MELD (Model for end-stage liver disease) score was 12.41 (Range 6.43–39.63). The quantification of sphingolipids in citrated plasma specimen was performed after methanolic protein precipitation followed by hydrophilic interaction liquid chromatography and tandem mass spectrometric detection. S1P and SA1P displayed significant correlations with the MELD score. Patients with circulating S1P levels below the lowest tertile (110.68 ng/ml) showed the poorest one-year survival rate of only 57.1%, whereas one-year survival rate in patients with S1P plasma levels above 165.67 ng/ml was 93.8%. In a multivariate cox regression analysis including platelet counts, concentrations of hemoglobin and MELD score, S1P remained a significant predictor for three-month and one-year mortality. Low plasma S1P concentrations are highly significantly associated with prognosis in end-stage liver disease. This association is independent of the stage of liver disease. Further studies should be performed to investigate S1P, its role in the pathophysiology of liver diseases and its potential for therapeutic interventions.