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Institute
Background and Objectives
Despite the long-standing consensus on the importance of tumor size, tumor number and carcinoembryonic antigen (CEA) levels as predictors of long-term outcomes among patients with colorectal liver metastases (CRLM), optimal prognostic cut-offs for these variables have not been established.
Methods
Patients who underwent curative-intent resection of CRLM and had available data on at least one of the three variables of interest above were selected from a multi-institutional dataset of patients with known KRAS mutational status. The resulting cohort was randomly split into training and testing datasets and recursive partitioning analysis was employed to determine optimal cut-offs. The concordance probability estimates (CPEs) for these optimal cut offs were calculated and compared to CPEs for the most widely used cut-offs in the surgical literature.
Results
A total of 1643 patients who met eligibility criteria were identified. Following recursive partitioning analysis in the training dataset, the following cut-offs were identified: 2.95 cm for tumor size, 1.5 for tumor number and 6.15 ng/ml for CEA levels. In the entire dataset, the calculated CPEs for the new tumor size (0.52), tumor number (0.56) and CEA (0.53) cut offs exceeded CPEs for other commonly employed cut-offs.
Conclusion
The current study was able to identify optimal cut-offs for the three most commonly employed prognostic factors in CRLM. While the per variable gains in discriminatory power are modest, these novel cut-offs may help produce appreciable increases in prognostic performance when combined in the context of future risk scores.
Acute post-operative delirium (POD) and long-term post-operative cognitive dysfunction (POCD) are frequent and associated with increased mortality, dependency on care giving and institutionalization rates. The POCD-related cost burden on the German long-term care insurance provides an indication for the savings potential from risk-adapted treatment schemes. Comprehensive estimates have not been assessed or published so far.
A model-based cost-analysis was designed to estimate POCD-related costs in the long-term care insurance. Comprehensive analysis of inpatient operations and procedures (OPS-codes) served as the base for case number calculations, which were then used as input to the actual cost model. POCD-incidence rates were obtained from the BioCog study. Various sensitivity analyses were performed to assess uncertainty of the model results.
Total POCD related annual costs in the German long-term care insurance account for approximately 1.6 billion EUR according to the base case of our analysis. Total annual costs for all POCD cases depend on surgery numbers, incidence rates, other assumptions, and uncertain input parameters.
The financial burden to the long-term care insurance is substantial, even in a conservative scenario of the cost model. Variability of results stems from uncertain assumptions, POCD-incidence rates and from uncertain patient numbers who are undergoing surgery and are therefore at risk to develop POCD.
Background
Postoperative delirium (POD) is a frequent and serious complication after surgery. Evidence of a relationship between anticholinergic medication and the development of delirium is inconclusive, but studies on POD are rare.
Objectives
The objective of this study was to evaluate the anticholinergic load of preoperative medication in older adult patients and its association with the development of POD.
Methods
This investigation was part of the European BioCog project (http://www.biocog.eu), a prospective multicenter observational study in older adult surgical patients (ClinicalTrials.gov identifier: NCT02265263, 15 October 2014). Patients with a Mini–Mental State Examination score ≤ 23 points were excluded. POD was assessed up to 7 days after surgery using the Nursing Delirium Screening Scale, Confusion Assessment Method and a patient chart review. The preoperative anticholinergic load was calculated using the Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS) and the Anticholinergic Cognitive Burden Scale (ACBS), and associations with POD were analyzed using logistic regression analysis adjusting for age, comorbidities, duration of anesthesia and number of drugs used.
Results
In total, 837 participants were included for analysis, and 165 patients (19.7%) fulfilled the criteria of POD. After adjusting for confounders, we found no association between preoperative anticholinergic load and the development of POD (ADS [points] odds ratio [OR] 0.928; 95% confidence interval [CI] 0.749–1.150; ARS [points] OR 0.832; 95% CI 0.564–1.227; ACBS [points] OR 1.045; 95% CI 0.842–1.296).
Conclusion
This study found no association between the anticholinergic load of drugs used preoperatively and the development of POD in older adult patients without severe preexisting cognitive impairment. Future analyses should examine the influence of intra- and postoperative administration of anticholinergic drugs as well as dosages of and interactions between medications.
Background: In longitudinal studies, observations are made over time. Hence, the single observations at each time point are dependent, making them a repeated measurement. In this work, we explore a different, counterintuitive setting: At each developmental time point, a lethal observation is performed on the pregnant or nursing mother. Therefore, the single time points are independent. Furthermore, the observation in the offspring at each time point is correlated with each other because each litter consists of several (genetically linked) littermates. In addition, the observed time series is short from a statistical perspective as animal ethics prevent killing more mother mice than absolutely necessary, and murine development is short anyway. We solve these challenges by using multiple contrast tests and visualizing the change point by the use of confidence intervals.
Results: We used linear mixed models to model the variability of the mother. The estimates from the linear mixed model are then used in multiple contrast tests.There are a variety of contrasts and intuitively, we would use the Changepoint method. However, it does not deliver satisfying results. Interestingly, we found two other contrasts, both capable of answering different research questions in change point detection: i) Should a single point with change direction be found, or ii) Should the overall progression be determined? The Sequen contrast answers the first, the McDermott the second. Confidence intervals deliver effect estimates for the strength of the potential change point. Therefore, the scientist can define a biologically relevant limit of change depending on the research question.
Conclusion: We present a solution with effect estimates for short independent time series with observations nested at a given time point. Multiple contrast tests produce confidence intervals, which allow determining the position of change points or to visualize the expression course over time. We suggest to use McDermott’s method to determine if there is an overall significant change within the time frame, while Sequen is better in determining specific change points. In addition, we offer a short formula for the estimation of the maximal length of the time series.
In this study the effect of PEF pre-treatment on the microstructure of freeze-dried strawberry dices was investigated. The PEF treatment has been performed at an electric field intensity of 1.07 kV/cm and a specific energy input of 1 kJ/kg. The samples were freeze-dried at a temperature of 45 °C and a pressure of 1 mbar. The microstructure of dried material was evaluated by different physical and optical methods, such as SEM, μ-CT and thermogravimetry. Moreover, mechanical and acoustic properties as well as the colour of processed material have been analyzed. PEF pre-treated strawberry dices showed a more uniform shape, a better retention of volume and a visual better quality compared to untreated ones. Moreover, PEF pre-treatment led to a more homogeneous distribution and a greater thickness of pores. In accordance, analysis of textural properties evidenced that PEF treated freeze-dried strawberry dices were crispier than untreated ones. Measurement of L*a*b*-values showed that PEF treated material was characterized by a more preserved colour after freeze-drying than untreated ones.
The apple fruit (Malus domestica L. Borkh) is one of the most popular fruits worldwide. Beyond their beneficial properties, apples contain proteins that trigger allergic reactions in susceptible consumers. Mal d1 to d4 are allergens present in a variety of different isoforms in apples. In this study, we used proteomics to quantify all four Mal d proteins in 52 apple genotypes with varying allergenic potentials. A total of 195, 17, 14, and 18 peptides were found to be related to Mal d1, d2, d3, and d4 proteins, respectively of which 25 different Mal d proteins could be unambiguously identified. The allergenic potential of the Mal d isoforms was characterized by comparing the isoform abundance with the allergenic score of genotypes from oral challenge tests. The detected Mal d peptides presumably have different IgE binding properties and could be used as potential molecular markers to discriminate between hypoallergenic and hyperallergenic cultivars.
Background:
Etomidate is typically used as an induction agent in cardiac surgery because it has little impact on hemodynamics. It is a known suppressor of adrenocortical function and may increase the risk for post-operative infections, sepsis, and mortality. The aim of this study was to evaluate whether etomidate increases the risk of postoperative sepsis (primary outcome) and infections (secondary outcome) compared to propofol.
Methods:
This was a retrospective before–after trial (IRB EA1/143/20) performed at a tertiary medical center in Berlin, Germany, between 10/2012 and 01/2015. Patients undergoing cardiac surgery were investigated within two observation intervals, during which etomidate and propofol were the sole induction agents.
Results:
One-thousand, four-hundred, and sixty-two patients, and 622 matched pairs, after caliper propensity-score matching, were included in the final analysis. Sepsis rates did not differ in the matched cohort (etomidate: 11.5% vs. propofol: 8.2%, p = 0.052). Patients in the etomidate interval were more likely to develop hospital-acquired pneumonia (etomidate: 18.6% vs. propofol: 14.0%, p = 0.031).
Conclusion:
Our study showed that a single-dose of etomidate is not statistically associated with higher postoperative sepsis rates after cardiac surgery, but is associated with a higher incidence of hospital-acquired pneumonia. However, there is a notable trend towards a higher sepsis rate.
Background:
Cardiac surgery patients represent a high-risk cohort in intensive care units (ICUs). Central venous pressure (CVP) measurement seems to remain an integral part in hemodynamic monitoring, especially in cardio-surgical ICUs. However, its value as a prognostic marker for organ failure is still unclear. Therefore, we analyzed postoperative CVP values after adult cardiac surgery in a large cohort with regard to its prognostic value for morbidity and mortality.
Methods:
All adult patients admitted to our ICUs between 2006 and 2019 after cardiac surgery were eligible for inclusion in the study (n = 11,198). We calculated the median initial CVP (miCVP) after admission to the ICU, which returned valid values for 9802 patients. An ROC curve analysis for optimal cut-off miCVP to predict ICU mortality was conducted with consecutive patient allocation into a (a) low miCVP (LCVP) group (≤11 mmHg) and (b) high miCVP (HCVP) group (>11 mmHg). We analyzed the impact of high miCVP on morbidity and mortality by propensity score matching (PSM) and logistic regression.
Results:
ICU mortality was increased in HCVP patients. In addition, patients in the HCVP group required longer mechanical ventilation, had a higher incidence of acute kidney injury, were more frequently treated with renal replacement therapy, and showed a higher risk for postoperative liver dysfunction, parametrized by a postoperative rise of ≥ 10 in MELD Score. Multiple regression analysis confirmed HCVP has an effect on postoperative ICU-mortality and intrahospital mortality, which seems to be independent.
Conclusions:
A high initial CVP in the early postoperative ICU course after cardiac surgery is associated with worse patient outcome. Whether or not CVP, as a readily and constantly available hemodynamic parameter, should promote clinical efforts regarding diagnostics and/or treatment, warrants further investigations.
Preoperative medication use and development of postoperative delirium and cognitive dysfunction
(2021)
Postoperative delirium (POD) and postoperative (neuro-)cognitive disorder (POCD) are frequent and serious complications after operations. We aim to investigate the association between pre-operative polypharmacy and potentially inappropriate medications and the development of POD/POCD in elderly patients. This investigation is part of the European BioCog project (www.biocog.eu), a prospective multicenter observational study with elderly surgical patients. Patients with a Mini-Mental State Examination score less than or equal to 23 points were excluded. POD was assessed up to 7 days after surgery using the Nursing Delirium Screening Scale, Confusion Assessment Method (for the intensive care unit [ICU]), and a patient chart review. POCD was assessed 3 months after surgery with a neuropsychological test battery. Pre-operative long-term medication was evaluated in terms of polypharmacy (≥5 agents) and potentially inappropriate medication (defined by the PRISCUS and European list of potentially inappropriate medications [EU(7)-PIM] lists), and associations with POD and POCD were analyzed using logistic regression analysis. Eight hundred thirty-seven participants were included for analysis of POD and 562 participants for POCD. Of these, 165 patients (19.7%) fulfilled the criteria of POD and 60 (10.7%) for POCD. After adjusting for confounders, pre-operative polypharmacy and intake of potentially inappropriate medications could not be shown to be associated with the development of POD nor POCD. We found no associations between pre-operative polypharmacy and potentially inappropriate medications and development of POD and POCD. Future studies should focus on the evaluation of drug interactions to determine whether patients benefit from a pre-operative adjustment.
The benzodiazepine, midazolam, is one of the most frequently used sedatives in intensive care medicine, but it has an unfavorable pharmacokinetic profile when continuously applied. As a consequence, patients are frequently prolonged and more deeply sedated than intended. Due to its distinct pharmacological features, including a cytochrome P450-independent metabolization, intravenous lormetazepam might be clinically advantageous compared to midazolam. In this retrospective cohort study, we compared patients who received either intravenous lormetazepam or midazolam with respect to their survival and sedation characteristics. The cohort included 3314 mechanically ventilated, critically ill patients that received one of the two drugs in a tertiary medical center in Germany between 2006 and 2018. A Cox proportional hazards model with mortality as outcome and APACHE II, age, gender, and admission mode as covariates revealed a hazard ratio of 1.75 [95% CI 1.46–2.09; p < 0.001] for in-hospital mortality associated with the use of midazolam. After additionally adjusting for sedation intensity, the HR became 1.04 [95% CI 0.83–1.31; p = 0.97]. Thus, we concluded that excessive sedation occurs more frequently in critically ill patients treated with midazolam than in patients treated with lormetazepam. These findings require further investigation in prospective trials to assess if lormetazepam, due to its ability to maintain light sedation, might be favorable over other benzodiazepines for sedation in the ICU.