Routine frailty assessment predicts postoperative complications in elderly patients across surgical disciplines - a retrospective observational study.

BACKGROUND: Frailty is a frequent and underdiagnosed functional syndrome involving reduced physiological reserves and an increased vulnerability against stressors, with severe individual and socioeconomic consequences. A routine frailty assessment was implemented at our preoperative anaesthesia clinic to identify patients at risk. OBJECTIVE: This study examines the relationship between frailty status and the incidence of in-hospital postoperative complications in elderly surgical patients across several surgical disciplines. DESIGN: Retrospective observational analysis. SETTING: Single center, major tertiary care university hospital. Data collection took place between June 2016 and March 2017. PATIENTS: Patients 65 years old or older were evaluated for frailty using Fried's 5-point frailty assessment prior to elective non-cardiac surgery. Patients were classified into non-frail (0 criteria, reference group), pre-frail (1-2 positive criteria) and frail (3-5 positive criteria) groups. MAIN OUTCOME MEASURES: The incidence of postoperative complications was assessed until discharge from the hospital, using the roster from the National VA Surgical Quality Improvement Program. Propensity score matching and logistic regression analysis were performed. RESULTS: From 1186 elderly patients, 46.9% were classified as pre-frail (n = 556), and 11.4% as frail (n = 135). The rate of complications were significantly higher in the pre-frail (34.7%) and frail groups (47.4%), as compared to the non-frail group (27.5%). Similarly, length of stay (non-frail: 5.0 [3.0;7.0], pre-frail: 7.0 [3.0;9.0], frail 8.0 [4.5;12.0]; p < 0.001) and discharges to care facilities (non-frail:1.6%, pre-frail: 7.4%, frail: 17.8%); p < 0.001) were significantly associated with frailty status. After propensity score matching and logistic regression analysis, the risk for developing postoperative complications was approximately two-fold for pre-frail (OR 1.78; 95% CI 1.04-3.05) and frail (OR 2.08; 95% CI 1.21-3.60) patients. CONCLUSIONS: The preoperative frailty assessment of elderly patients identified pre-frail and frail subgroups to have the highest rate of postoperative complications, regardless of age, surgical discipline, and surgical risk. Significantly increased length of hospitalisation and discharges to care facilities were also observed. Implementation of routine frailty assessments appear to be an effective tool in identifying patients with increased risk. Now future studies are needed to investigate whether patients benefit from optimization of patient counselling, process planning, and risk reduction protocols based on the application of risk stratification.

Validation of 3-minute diagnostic interview for CAM-defined Delirium to detect postoperative delirium in the recovery room: A prospective diagnostic study.

BACKGROUND: Recent guidelines on postoperative delirium (POD) recommend POD screening in all patients, using a validated tool, starting in the recovery room. An operationalisation of the Confusion Assessment Method (CAM) criteria, the 3-Minute Diagnostic Interview for CAM-defined Delirium (3D-CAM), has been developed for use in general medical units. OBJECTIVES: The aim of this study was to evaluate 3D-CAM performance in an adult patient population to detect POD in the recovery room. DESIGN: A prospective diagnostic study. SETTING: Recovery room of a tertiary care university hospital in Berlin, Germany, in 2017. PATIENTS: Patients at least 18 years of age undergoing elective surgery. MAIN OUTCOME MEASURES: Patients were subjected to evaluation by blinded investigators using the 3D-CAM and the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5, reference standard). Sensitivity, specificity and positive predictive value (PPV) and negative predictive value (NPV) were analysed for 3D-CAM, in addition to test-retest and inter-rater reliability analyses. RESULTS: Sixteen out of 176 patients (9.1%) developed POD. The 3D-CAM demonstrated strong test performance (specificity 0.88, sensitivity 1.0, area under the curve 0.94, PPV 0.44 and NPV 1.0), with a test-retest reliability of 90% (n = 10) and inter-rater reliability of 80% (n = 10). CONCLUSION: In this diagnostic study, 3D-CAM showed strong performance for detection of POD in the recovery room. Due to the low training requirements, fast application and high sensitivity, it might be particularly appropriate for clinical staff with limited experience in the assessment of POD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02992717.

Relevance of peripheral cholinesterase activity on postoperative delirium in adult surgical patients (CESARO): A prospective observational cohort study.

BACKGROUND: The cholinergic system is considered to play a key role in the development of postoperative delirium (POD), which is a common complication after surgery. OBJECTIVES: To determine whether peri-operative acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities are associated with the development of POD in in-hospital surgical patients, and raise hypotheses on cholinergic regulatory mechanisms in POD. DESIGN: A prospective multicentre observational study by the Peripheral Cholinesterase-activity on Neurocognitive Dysfunctions in Surgical Patients (CESARO) study group. SETTING: Nine German hospitals. PATIENTS: Patients of at least 18 years of age scheduled for inpatient elective surgery for a variety of surgical procedures. A total of 650 patients (mean age 61.5 years, 52.8% male) were included. METHODS: Clinical variables, and peripheral AChE and BuChE activities, were assessed throughout the peri-operative period using bedside point-of-care measurements (one pre-operative and two postoperative measurements). POD screening was conducted postoperatively for at least 24 h and up to the third postoperative day using a validated screening tool (nursing delirium screening scale). RESULTS: In all, 179 patients (27.5%) developed POD within the early postoperative phase. There was a lower BuChE activity in patients with delirium compared with patients without delirium pre-operatively (Cohen's r = 0.07, P = 0.091), on postoperative day 1 (Cohen's r = 0.12, P = 0.003) and on postoperative day 2 (Cohen's r = 0.12, P = 0.002). In contrast, there was a significantly higher AChE activity in patients with delirium compared with patients without delirium pre-operatively (Cohen's r = 0.10, P = 0.012), on postoperative day 1 (Cohen's r = 0.11, P = 0.004) and on postoperative day 2 (Cohen's r = 0.13, P = 0.002). After adjusting for covariates in multiple logistic regression, a significant association between both BuChE and AChE activities and POD was not found. However, in the multivariable analysis using the Generalized Estimating Equation, cholinesterase activities showed that a decrease of BuChE activity by 100 U L increased the risk of a delirium by approximately 2.1% (95% CI 1.6 to 2.8%) and for each 1 U g of haemoglobin increase in AChE activity, there was a 1.4% (95% CI 0.6 to 2.2%) increased risk of POD. CONCLUSION: Peri-operative peripheral cholinesterase activities may be related to the development of POD, but the clinical implications remain unclear. Further studies, in homogeneous patient groups with a strict protocol for measurement time points, are needed to investigate the relationship between cholinesterase activities and POD. TRIAL REGISTRATION: www.clinicaltrials.gov. Identifier NCT01964274.

[Perioperative Neurocognitive Disorders - Postoperative Prevention Strategies]. / Wie können postoperativ ein Delir und eine neurokognitive Störung verhindert werden?

Postoperative delirium (POD) is a common and serious complication after surgery. It is associated with increased morbidity and mortality as well as neurocognitive disorder and associated loss of autonomy and increased need for care. As professionals, it is our duty to treat our patients in a holistic individual concept with the aim to reintegrate our patients into their home and social environment afterwards. In addition to preoperative and intraoperative interventions, postoperative prevention is of particular importance. This article focuses on non-pharmacological prevention strategies to avoid postoperative delirium and neurocognitive disorder in postoperative inpatient care. It is based on the "Evidence-based and consensus-based guideline on postoperative delirium". Thus, risk factors are addressed and non-pharmacological strategies are presented, which include reorientation, mobilization and nutritional support. Interprofessional cooperation plays just as important a role as the implementation of the listed preventive measures. Finally, the modified Hospital Elder Life Program is presented, which presents and applies preventive measures as a system-oriented and interdisciplinary concept, which "prevents functional decline and allows older adults to return home at the maximal level of independence". From our point of view, the training of a professional delirium team is a future-oriented complementary measure in the treatment concept of Perioperative Neurocognitive Disorders (PND), which finds its justification as an interface in the treatment of high-risk patients.

[3D-CAM Guideline-Conform Translation for German-Speaking Countries]. / 3D-CAM: Delir-Testinstrument für deutschsprachigen Raum übersetzt.

Postoperative delirium (POD) is an acute change in the mental state with consciousness and attention deficits. It is a common complication after surgical procedures and can have serious consequences. Thus, the evidence- and consensus-based guidelines for POD appeals with the highest recommendation level that patients be regularly screened for delirium in the postoperative phase, from the recovery room to the fifth postoperative day and at least once per shift, using a validated test instrument for the detection of POD. In 2014, Marcantonio et al. published the 3D-CAM (3-Minute Diagnostic Interview for CAM-defined Delirium). In the 3D-CAM, the algorithm of the Confusion Assessment Method (CAM) is maintained by using individual elements that operationalize the evaluation of the criteria. Therefore, it requires less training, be faster to use, and, due to a standardized approach, has less interrater variability than the CAM, whereas the high sensitivity and specificity are maintained. Our goal was to translate the 3D-CAM from English to German, so as to make this instrument available to German-speaking countries. The translation of the 3D-CAM was based on the 2005 published guideline on Translation and Cultural Adaptation of Patient Reported Outcome Measures of the International Society for Pharmacoeconomics and Outcome Research. Three independent forward translations were harmonized to a preliminary translation, which then was translated back into the original language. Original authors reviewed the back translation. According to a cognitive debriefing, the translation was revised and in addition was adapted for use in the recovery room. Due to close contact with the original authors during the translation process, it was possible to ensure that the contents of the test instrument were remained intact during the translation process.

Functional assessment of genetic variants located in the promoter of SHP1 (NR0B2).

Small heterodimer partner 1 (SHP1, NR0B2) is a member of the superfamily of nuclear receptors (NRs). Even if this orphan receptor, unlike other NRs, lacks the DNA-binding domain, it is capable of regulating transcription by repressing the activity of other NRs by direct protein-protein interaction. Accordingly, SHP1 is part of negative feedback loops of the transcriptional regulation of genes involved in drug metabolism and various metabolic pathways including bile acid and glucose homeostasis. Although it is known that several interacting partners of SHP1 also modulate its expression, there is little information about genetic variability of this regulatory mechanism. Our study aimed to identify genetic variants in the NR0B2 promoter region and to determine their impact on NR0B2 transcription. For this, DNA samples originating from 119 participants of the population-based cohort Study of Health in Pomerania were analyzed by Sanger sequencing revealing four genetic variants: NR0B2:c.-594T>C (rs71636795), NR0B2:c.-414G>C (newly identified), NR0B2:c.-423C>T (rs78182695), and NR0B2:c.-224delCTGA (rs145613139) localized in the 5' untranslated region of NR0B2. The impact of these variants on transactivation of the NR0B2 promoter by NRs known to be regulators of SHP1 expression (hepatocyte nuclear factor 4α, liver receptor homolog-1, and farnesoid X receptor) was assessed in a cell-based reporter gene assay, showing that transactivation by hepatocyte nuclear factor 4α and liver receptor homolog-1 was significantly decreased in the presence of the genetic variant NR0B2:c.-594T>C, even though this effect was cell specific. However, SHP1 mRNA expression in a small collection of human kidney samples was not affected by these genetic variants.

[Why and How Should I Assess Frailty? A Guide for the Preoperative Anesthesia Clinic]. / Warum und wie sollte ich Frailty erfassen? ­ ein Ansatz für die Anästhesieambulanz.

Introduction: Frailty is a condition of decreased physiological reserves seen in approx. one third of elderly anesthesiological patients, and affecting many aspects of treatment as well as outcome. Although there are over 60 measurement instruments, frailty assessment is still poorly implemented. Understanding why and how to assess frailty is key to its implementation in preoperative anesthesia clinics. Method: After presenting the impact of perioperative frailty and the benefits of an early diagnosis on health related quality of life, we present an overview of the most important tools that can be used in the preoperative frailty assessment. Results: Early diagnosis offer several optimization opportunities for the perioperative period. The most efficient frailty assessment tools are presented and discussed, including physical, cognitive, and psychosocial aspects. Conclusion: Frailty assessments vary immensely in terms of required time, equipment, and expertise. We recommend at least one test for each domain of frailty, so as to obtain a more holistic view of the patient's physiological reserve. The implementation of an adequate and consistent preoperative frailty assessment has the potential to improve patient safety as well as short and long term outcomes.

Modulation of expression of the nuclear receptor NR0B2 (small heterodimer partner 1) and its impact on proliferation of renal carcinoma cells.

Mammalian nuclear receptors (NRs) are transcription factors regulating the expression of target genes that play an important role in drug metabolism, transport, and cellular signaling pathways. The orphan and structurally unique receptor small heterodimer partner 1 (syn NR0B2) is not only known for its modulation of drug response, but has also been reported to be involved in hepatocellular carcinogenesis. Indeed, previous studies show that NR0B2 is downregulated in human hepatocellular carcinoma, suggesting that NR0B2 acts as a tumor suppressor via inhibition of cellular growth and activation of apoptosis in this tumor entity. The aim of our study was to elucidate whether NR0B2 may also play a role in other tumor entities. Comparing NR0B2 expression in renal cell carcinoma and adjacent nonmalignant transformed tissue revealed significant downregulation in vivo. Additionally, the impact of heterologous expression of NR0B2 on cell cycle progression and proliferation in cells of renal origin was characterized. Monitoring fluorescence intensity of resazurin turnover in RCC-EW cells revealed no significant differences in metabolic activity in the presence of NR0B2. However, there was a significant decrease of cellular proliferation in cells overexpressing this NR, and NR0B2 was more efficient than currently used antiproliferative agents. Furthermore, flow cytometry analysis showed that heterologous overexpression of NR0B2 significantly reduced the amount of cells passing the G1 phase, while on the other hand, more cells in S/G2 phase were detected. Taken together, our data suggest that downregulation of NR0B2 may also play a role in renal cell carcinoma development and progression.