Estimating patients' risk for postoperative delirium from preoperative routine data - Trial design of the PRe-Operative prediction of postoperative DElirium by appropriate SCreening (PROPDESC) study - A monocentre prospective observational trial.

BACKGROUND: Postoperative Delirium (POD) is the most common complication of elderly patients after surgery associated with increased postoperative morbidity, persistent care dependency and even mortality. Prevention of POD requires detection of patients at high risk prior to surgery. PROPDESC intends to provide an instrument for preoperative routine screening of patients' risk for POD. METHODS: PROPDESC is a monocentric prospective observatory trial including 1000 patients older than 60 years from various disciplines of a university hospital planned for surgery of at least 60 min. To develop a score predicting the risk for POD, anesthesiological stratifications, laboratory values, medication and known risk factors as well as quality of life and cognitive performance are taken into account. POD assessment is performed daily on the first five days after the operation respectively the end of sedation in the intensive care units and normal wards. The score is evaluated from 600 data sets and subsequently validated internally. The most appropriate predictors are determined by a component-wise gradient boosting approach. DISCUSSION: Based on retrospective investigations, etiology of POD is considered multifactorial. By a prospective analysis of various factors, PROPDESC intends to provide an applicable tool to predict the risk for POD from preoperative routine data and assessment of cognitive function. Objective is to establish an automatically generating score in preoperative routine to screen patients for increased risk of POD as starting point for POD reduction and management. Model compilation requires a high significance and enhancement within compound as well as regular availability of the selected predictors. TRIAL REGISTRATION: DRKS, DRKS00015715. Registered 13 December 2018 - Retrospectively registered, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015715.

The signalling molecule Autoinducer-2 is not internalised in Campylobacter jejuni.

Bacteria recognise and constantly adjust to changing situations by sensing environmental and self-produced signals. Autoinducer-2 (AI-2) is a signal molecule, found in many bacterial species and thus proposed to enable interspecies com- munication. Two classes of AI-2 receptors have been identified so far. One class of AI-2 receptors sense AI-2 by a two component signalling system.The other class, the LsrB family, internalises and phosphorylates AI-2. Campylobacter (C.) jejuni is known to produce AI-2, but no AI-2 receptor in C. jejuni has been found yet.Therefore, all research on AI-2 dependent phenotypes has been conducted with AI-2 synthase (luxS) mutants. This mutation also leads to a disruption of the activated methyl cycle. Most studies lack sufficient complementation result- ing in not knowing whether phenotypes of luxS mutants depend on disrupted metabolism or lack of AI-2. All this contributes to an intensive discussion, about the exact role of AI-2 in C. jejuni. Our previous study showed altering phenotypes (growth and motility) of the Cjejuni NCTC 11168ΔluxS mutant in contrast to wild type, which could be complemented with synthetic AI-2. To assess how AI-2 induces the altering phenotypes during complementation assays, we performed an AI-2 uptake assay. Our data show, that AI-2 is not internalised by C. jejuni.These data suggest, that yet unknown AI-2 receptors are present on the cell surface of C. jejuni. Therefore further search of AI-2 receptors in C. jejuni should focus on two component signalling systems and not on transporter systems.

Phenotypes of Campylobacter jejuni luxS mutants are depending on strain background, kind of mutation and experimental conditions.

Since the discovery that Campylobacter (C.) jejuni produces Autoinducer 2 (AI-2), various studies have been conducted to explore the function and role of AI-2 in C. jejuni. However, the interpretation of these analyses has been complicated by differences in strain backgrounds, kind of mutation and culture conditions used. Furthermore, all research on AI-2 dependent phenotypes has been conducted with AI-2 synthase (luxS) mutants. This mutation also leads to a disruption of the activated-methyl-cycle. Most studies lack sufficient complementation resulting in not knowing whether phenotypes of luxS mutants depend on disrupted metabolism or lack of AI-2. Additionally, no AI-2 receptor has been found yet. All this contributes to an intensive discussion about the exact role of AI-2 in C. jejuni. Therefore, we examined the impact of different experiment settings on three different C. jejuni luxS mutants on growth and motility (37°C and 42°C). Our study showed that differing phenotypes of C. jejuni luxS mutants depend on strain background, mutation strategy and culture conditions. Furthermore, we complemented experiments with synthetic AI-2 or homocysteine as well as the combination of both. Complementation with AI-2 and AI-2+homocysteine significantly increased the cell number of C. jejuni NCTC 11168ΔluxS in stationary phase compared to the non-complemented C. jejuni NCTC 11168ΔluxS mutant. Genetic complementation of both C. jejuni 81-176 luxS mutants resulted in wild type comparable growth curves. Also swarming ability could be partially complemented. While genetic complementation restored swarming abilities of C. jejuni 81-176ΔluxS, it did not fully restore the phenotype of C. jejuni 81-176::luxS, which indicates that compensatory mutations in other parts of the chromosome and/or potential polar effects may appear in this mutant strain. Also with neither synthetic complementation, the phenotype of the wild type-strains was achieved, suggesting yet another reason for differing phenotypes other than communication and methionine metabolism for C. jejuni luxS mutants.

Prognostic stratification of metastatic gastroenteropancreatic neuroendocrine neoplasms by 18F-FDG PET: feasibility of a metabolic grading system.

UNLABELLED: The tumor proliferation marker, Ki-67 index, is a well-established prognostic marker in gastroenteropancreatic neuroendocrine neoplasms (NENs). Noninvasive molecular imaging allows whole-body metabolic characterization of metastatic disease. We investigated the prognostic impact of (18)F-FDG PET in inoperable multifocal disease. METHODS: Retrospective, dual-center analysis was performed on 89 patients with histologically confirmed, inoperable metastatic gastroenteropancreatic NENs undergoing (18)F-FDG PET/CT within the staging routine. Metabolic (PET-based) grading was in accordance with the most prominent (18)F-FDG uptake (reference tumor lesion): mG1, tumor-to-liver ratio of maximum standardized uptake value ≤ 1.0; mG2, 1.0-2.3; mG3, >2.3. Other potential variables influencing overall survival, including age, tumor origin, performance status, tumor burden, plasma chromogranin A (≥600 µg/L), neuron-specific enolase (≥25 µg/L), and classic grading (Ki-67-based) underwent univariate (log-rank test) and multivariate analysis (Cox proportional hazards model), with a P value of less than 0.05 considered significant. RESULTS: The median follow-up period was 38 mo (95% confidence interval [CI], 27-49 mo); median overall survival of the 89 patients left for multivariate analysis was 29 mo (95% CI, 21-37 mo). According to metabolic grading, 9 patients (10.2%) had mG1 tumors, 22 (25.0%) mG2, and 57 (64.8%) mG3. On multivariate analysis, markedly elevated plasma neuron-specific enolase (P = 0.016; hazard ratio, 2.9; 95% CI, 1.2-7.0) and high metabolic grade (P = 0.015; hazard ratio, 4.7; 95% CI, 1.2-7.0) were independent predictors of survival. CONCLUSION: This study demonstrated the feasibility of prognostic 3-grade stratification of metastatic gastroenteropancreatic NENs by whole-body molecular imaging using (18)F-FDG PET.