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Institute
- Fakultät AuL (146) (remove)
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
There is no consensus on the instruments for diagnosis of post-intensive care syndrome (PICS). We present a proposal for a set of outcome measurement instruments of PICS in outpatient care.
Methods
We conducted a three-round, semi-structured consensus-seeking process with medical experts, followed each by exploratory feasibility investigations with intensive care unit survivors (n1 = 5; n2 = 5; n3 = 7). Fourteen participants from nine stakeholder groups participated in the first and second consensus meeting. In the third consensus meeting, a core group of six clinical researchers refined the final outcome measurement instrument set proposal.
Results
We suggest an outcome measurement instrument set used in a two-step process. First step: Screening with brief tests covering PICS domains of (1) mental health (Patient Health Questionnaire-4 (PHQ-4)), (2) cognition (MiniCog, Animal Naming), (3) physical function (Timed Up-and-Go (TUG), handgrip strength), and (4) health-related quality of life (HRQoL) (EQ-5D-5L). Single items measure subjective health before and after the intensive care unit stay. If patients report new or worsened health problems after intensive care unit discharge and show relevant impairment in at least one of the screening tests, a second extended assessment follows: (1) Mental health (Patient Health Questionnaire-8 (PHQ-8), Generalized Anxiety Disorder Scale-7 (GAD-7), Impact of Event Scale – revised (IES-R)); (2) cognition (Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Trail Making Test (TMT) A and B); (3) physical function (2-Minute Walk Test (2-MWT), handgrip strength, Short Physical Performance Battery (SPPB)); and (4) HRQoL (EQ-5D-5L, 12-Item WHO Disability Assessment Schedule (WHODAS 2.0)).
Conclusions
We propose an outcome measurement instrument set used in a two-step measurement of PICS, combining performance-based and patient-reported outcome measures. First-step screening is brief, free-of-charge, and easily applicable by health care professionals across different sectors. If indicated, specialized healthcare providers can perform the extended, second-step assessment. Usage of the first-step screening of our suggested outcome measurement instrument set in outpatient clinics with subsequent transfer to specialists is recommended for all intensive care unit survivors. This may increase awareness and reduce the burden of PICS.
Background
A pre-existing neurocognitive disorder (NCD) is a relevant factor for the outcome of surgical patients. To improve understanding of these conditions, we investigated the association between parameters of the cholinergic system and NCD.
Method
This investigation is part of the BioCog project (www.biocog.eu), which is a prospective multicenter observational study including patients aged 65 years and older scheduled for elective surgery. Patients with a Mini-Mental State Examination (MMSE) score ≤23 points were excluded. Neurocognitive disorder was assessed according to the fifth Diagnostic and Statistical Manual of Mental Disorders criteria. The basal forebrain cholinergic system volume (BFCSV) was assessed with magnetic resonance imaging, the peripheral cholinesterase (ChE) activities with point-of-care measurements, and anticholinergic load by analyzing the long-term medication with anticholinergic scales (Anticholinergic Drug Scale [ADS], Anticholinergic Risk Scale [ARS], Anticholinergic Cognitive Burden Scale [ACBS]). The associations of BFCSV, ChE activities, and anticholinergic scales with NCD were studied with logistic regression analysis, adjusting for confounding factors.
Results
A total of 797 participants (mean age 72 years, 42% females) were included. One hundred and eleven patients (13.9%) fulfilled criteria for mild NCD and 82 patients (10.3%) for major NCD criteria. We found that AcetylChE activity was associated with major NCD (odds ratio [95% confidence interval]: [U/gHB] 1.061 [1.010, 1.115]), as well as ADS score ([points] 1.353 [1.063, 1.723]) or ARS score, respectively ([points] 1.623 [1.100, 2.397]) with major NCD. However, we found no association between BFCSV or ButyrylChE activity with mild or major NCD.
Conclusions
AcetylChE activity and anticholinergic load were associated with major NCD. Future research should focus on the association of the cholinergic system and the development of postoperative delirium and postoperative NCD.
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 effect of pulsed electric field (PEF) and ultrasound (US) on the frying behavior of potato chips was investigated. For this purpose, a special fryer with a window was designed to enable the investigation of water evaporation by the characterization of bubble formation during frying. The number of water vapor bubbles and the bubble volume distribution were analyzed in order to gain an insight into heat and mass transfer affected by PEF and US treatment. Quality parameters of the potato chips such as moisture, fat and acrylamide content were measured. Overall, the results of this study show for the first time impacting effects on the frying process that can be achieved by combining PEF as a volumetric cell disintegration technology and ultrasound as a mean to affect interface phenomena. The obtained results can be used to further optimize frying processes used for the production of chips and other products.
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.
Currently, only non-imaging chlorophyll fluorescence measurements are used to identify the Lower Oxygen Limit (LOL) in Dynamic Controlled Atmosphere - Chlorophyll Fluorescence (DCA-CF) storage. The disadvantage of non-imaging fluorescence is that no statement can be made about the spatial heterogeneity of the sample. In contrast, chlorophyll fluorescence imaging can detect spatial heterogeneity of photosynthetic activity and has been established in research for some decades because the information benefit is higher. In this study, the chlorophyll fluorescence (Fo, Fm, Fv, Fv/Fm) of apples (Malus x domestica, BORKH.) was measured with a fluorescence imaging system in situ during storage. Intact apples of ‘Braeburn’ and ‘Golden Delicious’ were stored under low-oxygen stress conditions (< 1 kPa). The metabolic shift from aerobic to fermentative metabolism was made visible with the chlorophyll fluorescence imaging and was spatially localized on the sample. Furthermore, a method was developed to identify the LOL based on the chlorophyll fluorescence imaging combined with the histogram division method. This method considers the heterogeneity of the fluorescence and bundles the measured Fo data as histograms. Our results showed that the fluorescence imaging combined with the histogram division method can be a powerful tool for identifying the LOL.