Fever and hypothermia represent two populations of sepsis patients and are associated with outside temperature

Abstract Background Fever and hypothermia have been observed in septic patients. Their influence on prognosis is subject to ongoing debates. Methods We did a secondary analysis of a large clinical dataset from a quality improvement trial. A binary logistic regression model was calculated to assess the association of the thermal response with outcome and a multinomial regression model to assess factors associated with fever or hypothermia. Results With 6542 analyzable cases we observed a bimodal temperature response characterized by fever or hypothermia, normothermia was rare. Hypothermia and high fever were both associated with higher lactate values. Hypothermia was associated with higher mortality, but this association was reduced after adjustment for other risk factors. Age, community-acquired sepsis, lower BMI and lower outside temperatures were associated with hypothermia while bacteremia and higher procalcitonin values were associated with high fever. Conclusions Septic patients show either a hypothermic or a fever response. Whether hypothermia is a maladaptive response, as indicated by the higher mortality in hypothermic patients, or an adaptive response in patients with limited metabolic reserves under colder environmental conditions, remains an open question. Trial registration The original trial whose dataset was analyzed was registered at ClinicalTrials.gov (NCT01187134) on August 23, 2010, the first patient was included on July 1, 2011

Time-Specific Metalearners for the Early Prediction of Sepsis

Motivation: Accounting for complex clinical dynamics in sepsis patients while aiming at an automated analysis of hourly (non-)validated data is challenging. The algorithm has to deal with imprecise, incorrect and incomplete data in addition to being time aware. Methods: We aimed to build time-specific stacked ensembles and a non-specific XGBoost learner to predict sepsis 6 hours prior to the sepsis onset. The models were trained on a triple split of 40,336 ICU stays taken from the training sets of the 2019 PhysioNet/CinC Challenge. Data was cleaned and features were built based on rolling windows including several clinical scores and criteria, such as shock index, qSOFA, SOFA, SIRS, NEWS, cNEWS. Model performance was evaluated using task-specific utility functions. Furthermore, variable importance was assessed. Results and conclusion: Although no official score was obtained in the Challenge as team Sepsis2G, we found normalized utility score of 0.394 for our non-specific XGBoost model on a held out subset of the training data. The threshold selection was displaced in time-specific metalearners leading to an inferior performance. Most important variables included the assumed presence of ventilation, white blood cell count, partial thromboplastin time, blood urea nitrogen and rolling quantiles of the temperature. Partial SOFA-scores, cNEWS, and the shock index showed major importance in the ICU admission phase

Whole genome expression analyses of single- and double-knock-out mice implicate partially overlapping functions of alpha- and gamma-synuclein

α-Synuclein has been implicated in the pathogenesis of Parkinson’s disease. The function of α-synuclein has not been deciphered yet; however, it might play a role in vesicle function, transport, or as a chaperone. α-Synuclein belongs to a family of three proteins, which includes β- and γ-synuclein. γ-Synuclein shares 60% similarity with α-synuclein. Similar to α-synuclein, a physiological function for γ-synuclein has not been defined yet, but it has been implicated in tumorgenesis and neurodegeneration. Interestingly, neither α- (SNCA−/−), γ- (SNCG−/−), nor α/γ- (SNCA_G−/−) deficient mice are present with any obvious phenotype. Using microarray analysis, we thus investigated whether deficiency of α- and γ-synuclein leads to similar compensatory mechanisms at the RNA level and whether similar transcriptional signatures are altered in the brain. Sixty-five genes were differentially expressed in all mice. SNCA−/− mice and SNCG−/− mice shared 84 differentially expressed genes, SNCA−/− and SNCA_G−/− expressed 79 genes, and SNCG−/− and SNCA_G−/− expressed 148 genes. For many of the physiological pathways such as dopamine receptor signaling (down-regulated), cellular development, nervous system function, and cell death (up-regulated), we found groups of genes that were similarly altered in SNCA−/− and SNCG−/− mice. In one of the pathways altered in both models, we found Mapk1 as the core transcript. Other gene groups, however, such as TGF-β signaling and apoptosis pathways genes were significantly up-regulated in the SNCA−/− mice but down-regulated in SNCG−/− mice. β-synuclein expression was not significantly altered in any of the models

Staphylococcus aureus Alpha-Toxin in Deep Tracheal Aspirates—Preliminary Evidence for Its Presence in the Lungs of Sepsis Patients

The pore forming alpha-toxin (hemolysin A, Hla) of Staphylococcus aureus (S. aureus) is a major virulence factor with relevance for the pathogenicity of this bacterium, which is involved in many cases of pneumonia and sepsis in humans. Until now, the presence of Hla in the body fluids of potentially infected humans could only be shown indirectly, e.g., by the presence of antibodies against Hla in serum samples or by hemolysis testing on blood agar plates of bacterial culture supernatants of the clinical isolates. In addition, nothing was known about the concentrations of Hla actually reached in the body fluids of the infected hosts. Western blot analyses on 36 samples of deep tracheal aspirates (DTA) isolated from 22 hospitalized sepsis patients using primary antibodies against different epitopes of the Hla molecule resulted in the identification of six samples from five patients containing monomeric Hla (approx. 33 kDa). Two of these samples showed also signals at the molecular mass of heptameric Hla (232 kDa). Semiquantitative analyses of the samples revealed that the concentrations of monomeric Hla ranged from 16 to 3200 ng/mL. This is, to our knowledge, the first study directly showing the presence of S. aureus Hla in samples of airway surface liquid in human patients