Study of Early Elevated Gas6 Plasma Level as a Predictor of Mortality in a Prospective Cohort of Patients with Sepsis.

Growth arrest-specific gene 6 (Gas6), a vitamin K-dependent protein interacting with anionic phospholipids and TAM tyrosine kinase receptors, is elevated in plasma of septic patients. Previous studies did not find different levels between survivors and non-survivors at admission because either they included a low number of patients (<50) or a low number of non-survivors (5%). To determine, in a larger cohort of septic patients comprising an expected number of non-survivors, the performance of the plasma level of Gas6 and its soluble receptor Axl (sAxl) within 24 hours of admission to predict in-ICU mortality. Septic adults with or without shock. Gas6 and sAxl were prospectively measured by ELISA at day 0, 3, 7, and then weekly until discharge or death. We evaluated 129 septic patients, including 82 with and 47 without shock, with in-ICU mortality rate of 19.4% and in-hospital mortality rate of 26%. Gas6 level was higher in non-survivors than in survivors (238 vs. 167%, P = 0.003); this difference remained constant during the ICU stay. The area under the ROC curve for Gas6 (0.695 [95% CI: 0.58-0.81]) was higher than for sAxl, procalcitonin, CRP, IL-1beta, IL-6 and-alpha, and slightly higher than for IL-8, IL-10, SOFA and APACHEII scores in predicting in-ICU mortality. Considering 249% as a cut-off value, Gas6 measurement had a negative predictive value for mortality of 87%. It seems that Gas6 plasma level within 24 hours of ICU admission may predicts in-ICU mortality in patients with sepsis. If our result are confirmed in external validation, Gas6 plasma level measurement could contribute to the identification of patients who may benefit most from more aggressive management

Autochthonous production sustains food webs in large perialpine lakes, independent of trophic status: Evidence from amino acid stable isotopes

Lakes are recipients of allochthonous organic matter and nutrients. However, the importance of these subsidies for food webs and how they vary with lake trophic status remains unclear, especially for large lakes. We assessed the source and fate of organic matter and nutrients in seven perialpine lakes across a gradient of trophic status. We measured carbon and nitrogen stable isotopes of amino acids of lake-residing Atlantic trout, Salmo trutta, to determine the source of primary production (i.e., how carbon is fixed in the ecosystem) and how it is transferred through food webs, respectively. Based on essential amino acid carbon fingerprinting, we estimated the probability of organic carbon originating from autochthonous (algal), allochthonous (terrestrial plant), and recycled (bacterial) sources. In addition, we used amino acid delta N-15 to track how this primary production is transferred to consumers in general, and by using different trophic amino acids (glutamic acid and alanine), identify the trophic pathways involving either metazoan or protozoans. We found a high likelihood of autochthonous origin of organic carbon (86 +/- 9%) in trout that contrasted with allochthonous origins of particulate organic matter and some sediments. We showed that those estimates are good proxies of source reliance. Our results also highlighted the importance of bacterial origin of organic carbon in fish (12%). The likely autochthonous origin of this carbon was supported by trophic markers (Ala delta N-15) that suggest the role of protists in transferring recycled organic carbon up the food web. While the sources of nitrogen sustaining food webs varied among lakes, we found a conserved carbon fingerprinting of fish. Overall, this suggests an uncoupling between the source of nutrients and organic carbon in large perialpine lakes. Across a wide range of trophic status (c. 2 orders of magnitude range of phosphorus concentration), several lines of evidence suggested that perialpine lake food webs shared a common reliance on autochthonous and bacterial production. Our study is the first to quantify the dependence on allochthonous organic carbon in lake food webs based on new amino acid stable isotope markers (carbon fingerprinting and Ala delta N-15) and shows promise for estimating the source of carbon fixation in ecosystems. Our results support previous suggestions that terrestrial organic carbon is a relatively minor source for aquatic consumers despite contributing to the pool of organic matter, and more importantly, its contribution does not vary substantially with trophic status in perialpine lakes.ISSN:0046-5070ISSN:1365-242

Value of SUVmax for the prediction of bone invasion in oral squamous cell carcinoma

In advanced oral squamous cell carcinoma (OSCC), accurate planning of surgical resection and reconstruction are crucial for outcome and postoperative function. For OSCC close to the maxilla or mandible, prediction of bone invasion is necessary. The aim of this study was to examine whether metabolic tumor imaging obtained by fluorodeoxyglucose positron emission tomography (FDG-PET) could enhance preoperative predictability of bone invasion. We performed an analysis of 84 treatment-naïve OSCCs arising from gum (upper and lower), hard palate, floor of mouth, and retromolar trigone treated at the University Hospital Zurich, Switzerland, who underwent wide local excision with free flap reconstruction between 04/2010 and 09/2018 and with available preoperative FDG-PET. Prediction of bone invasion by metabolic tumor imaging such as maximum standardized uptake value (SUVmax) was examined. On definitive histopathology, bone invasion was present in 47 of 84 cases (56%). The probability of bone infiltration increased with a higher pretherapeutic SUVmax in an almost linear manner. A pretherapeutic SUVmax of primary tumor below 9.5 ruled out bone invasion preoperatively with a high specificity (97.6%). The risk of bone invasion was 53.6% and 71.4% for patients with SUVmax between 9.5-14.5 and above 14.5, respectively. Patients with bone invasion had worse distant metastasis-free survival compared to patients without bone invasion (log-rank test, p = 0.032). In conclusion, metabolic tumor imaging using FDG-PET could be used to rule out bone invasion in oral cancer patients and may serve in treatment planning

Severe Late-Onset Drug-Induced Immune Thrombocytopenia Following IFN β-1a Treatment: A Case Report of a 52-Year-Old Woman with Relapse-Remitting Multiple Sclerosis

Interferon β-1a (IFNβ1a) is considered safe in relapsing-remitting multiple sclerosis (RRMS). Drug-induced thrombocytopenia (DITP) is a rare but underreported adverse event that is often confused with other causes of thrombocytopenia. We report the case of a 52-year-old woman who developed limb and oral mucosa petechiae and hematochezia, 10 years after beginning IFNβ1a. Blood work showed an isolated severe thrombocytopenia and ruled out other autoimmune diseases, viral infections, intravascular hemolysis, and renal impairment. Oral corticosteroids and tranexamic acid were initiated with a favorable platelet response. IFNβ1a was resumed, leading to recurrence of thrombocytopenia. Platelets came back to normal after intravenous immunoglobulins and IFNβ1a was definitively discontinued. To our knowledge, this is the first case of drug-induced immune thrombocytopenia (DITP) associated with IFNβ1a

Correction: Stalder, et al.; Value of SUVmax for the Prediction of Bone Invasion in Oral Squamous Cell Carcinoma. Biology 2020, 9, 23

The authors would like to make a correction to their published paper [1][...]