The association between frailty and MRI features of cerebral small vessel disease

Abstract: Frailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype

Influence of postoperative immune stimulation with GM-CSF versus placebo on the CD4+-subpopulation IFN-γ-producing Th1 cells in consideration of transcription factors STAT1 and T-bet

Einleitung: Eine postoperative Immunsuppression führt zu einem erhöhten Risiko für infektiöse Komplikationen bei Patienten. Durch eine frühzeitige Erfassung von Risikopatienten können Maßnahmen, wie z.B. die Gabe immunstimulatorischer Medikamente eingeleitet werden. Ziel dieser Arbeit war es, den Effekt einer Therapie mit GM-CSF auf T-Helferzellen vom Typ 1 (Th1-Zellen) zu untersuchen. Th1-Zellen sind eine Untergruppe der T-Helferzellen (Th-Zellen) mit Funktionen in der Abwehr von Erregern und entzündlichen Prozessen. Methoden: Untersucht wurden jeweils 10 Patienten der GM-CSF bzw. der Placebogruppe in einer randomisierten kontrollierten Studie, die sich elektiv einer Pankreas- oder Ösophagusresektion unterzogen und postoperativ eine Expression von HLA-DR unter 10.000 Antigene/Monozyt hatten. Die Bestimmung der Th1-Zellen erfolgte am Operationstag (OD) und an fünf postoperativen Tagen (POD1-5) durch Messungen der für die Th1-Zellen spezifischen Transkriptionsfaktoren STAT1 und T-bet mittels Real-time PCR, sowie durch Messung der Sezernierung des Zytokins IFN-γ in T-helfer Zellen nach einer ex vivo Stimulation von isolierten PBMCs am Durchflusszytometer. Ergebnisse: Die Studienergebnisse zeigten in der GM- CSF-Gruppe am zweiten (p=0.008) und dritten postoperativen Tag (p=0.028) eine signifikant erhöhte Genexpression des Transkriptionsfaktors STAT1 im Vergleich zur Placebogruppe. Die Genexpression für T-bet und der Anteil an IFN-γ sezernierenden Th1-Zellen zeigte in der GM-CSF Gruppe im postoperativen Verlauf einen Anstieg, jedoch gab es keine signifikanten Unterschiede im Vergleich zur Placebogruppe. Schlussfolgerung: In der vorliegenden Arbeit konnte ein signifikanter Effekt in der GM-CSF-Gruppe in der Expression des Transkriptionsfaktors STAT1 im Vergleich zur Placebogruppe detektiert werden. Schlüsselwörter: STAT1, T-bet, Th1-Zellen, GM-CSF, IFN-γ, HLA-DRIntroduction: Postoperative immunosuppression leads to an increased risk of infectious complications in patients. Through early detection of patients at risk, measures such as the administration of immunostimulatory drugs, can be initiated. The aim of this study was to investigate the effect of GM-CSF treatment in T-helper cell type 1 (Th1) cells. Th1 cells are a subset of T-helper cells (Th), with functions in the defense against pathogens and inflammatory processes. Methods: 10 patients from each of GM-CSF and placebo group were examined in a randomized controlled trial, who electively underwent pancreatic or esophageal resection and whose postoperative expression of HLA- DR antigens was below 10.000 antigen/monocyte. The determination of Th1 cells was carried out the day of surgery (OD) and at five postoperative days (POD1-5) by measurements of the Th1 cell-specific transcription factors STAT1 and T-bet using real-time PCR, and by measuring secretion of cytokine IFN-γ in Th cells after ex vivo stimulation of isolated PBMCs by flow cytometry. Results: The study results showed a significantly increased expression of the transcription factor STAT1 in the GM-CSF group on the second (p = 0.008) and third postoperative day (p = 0.028) compared to the placebo group. The expression of T-bet and the rate of IFN-γ secreting Th1 cells showed an upsurge in the GM-CSF group during the postoperative period however without significant differences compared to the placebo group. Conclusion: In the present work, a significant effect on the transcription factor STAT1 expression in the GM-CSF group compared to the placebo group could be detected. Keywords: STAT1, T-bet, Th1 cells, GM-CSF, IFN-γ, HLA-D

Perioperative Electroencephalogram Spectral Dynamics Related to Postoperative Delirium in Older Patients

BACKGROUND: Intraoperative electroencephalography (EEG) signatures related to the development of postoperative delirium (POD) in older patients are frequently studied. However, a broad analysis of the EEG dynamics including preoperative, postinduction, intraoperative and postoperative scenarios and its correlation to POD development is still lacking. We explored the relationship between perioperative EEG spectra-derived parameters and POD development, aiming to ascertain the diagnostic utility of these parameters to detect patients developing POD. METHODS: Patients aged ≥65 years undergoing elective surgeries that were expected to last more than 60 minutes were included in this prospective, observational single center study (Biomarker Development for Postoperative Cognitive Impairment [BioCog] study). Frontal EEGs were recorded, starting before induction of anesthesia and lasting until recovery of consciousness. EEG data were analyzed based on raw EEG files and downloaded excel data files. We performed multitaper spectral analyses of relevant EEG epochs and further used multitaper spectral estimate to calculate a corresponding spectral parameter. POD assessments were performed twice daily up to the seventh postoperative day. Our primary aim was to analyze the relation between the perioperative spectral edge frequency (SEF) and the development of POD. RESULTS: Of the 237 included patients, 41 (17%) patients developed POD. The preoperative EEG in POD patients was associated with lower values in both SEF (POD 13.1 ± 4.6 Hz versus no postoperative delirium [NoPOD] 17.4 ± 6.9 Hz; P = .002) and corresponding γ-band power (POD -24.33 ± 2.8 dB versus NoPOD -17.9 ± 4.81 dB), as well as reduced postinduction absolute α-band power (POD -7.37 ± 4.52 dB versus NoPOD -5 ± 5.03 dB). The ratio of SEF from the preoperative to postinduction state (SEF ratio) was ~1 in POD patients, whereas NoPOD patients showed a SEF ratio >1, thus indicating a slowing of EEG with loss of unconscious. Preoperative SEF, preoperative γ-band power, and SEF ratio were independently associated with POD (P = .025; odds ratio [OR] = 0.892, 95% confidence interval [CI], 0.808-0.986; P = .029; OR = 0.568, 95% CI, 0.342-0.944; and P = .009; OR = 0.108, 95% CI, 0.021-0.568, respectively). CONCLUSIONS: Lower preoperative SEF, absence of slowing in EEG while transitioning from preoperative state to unconscious state, and lower EEG power in relevant frequency bands in both these states are related to POD development. These findings may suggest an underlying pathophysiology and might be used as EEG-based marker for early identification of patients at risk to develop POD

A Model-Based Estimation of Annual Long-Term Care Costs in Germany Following Post-Operative Cognitive Dysfunction (POCD) in Elderly Patients

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

Quality contract ‘prevention of postoperative delirium in the care of elderly patients’ study protocol : a non-randomised, pre–post, monocentric, prospective trial

Introduction Postoperative delirium (POD) is seen in approximately 15% of elderly patients and is related to poorer outcomes. In 2017, the Federal Joint Committee (Gemeinsamer Bundesausschuss) introduced a ‘quality contract’ (QC) as a new instrument to improve healthcare in Germany. One of the four areas for improvement of in-patient care is the ‘Prevention of POD in the care of elderly patients’ (QC-POD), as a means to reduce the risk of developing POD and its complications. The Institute for Quality Assurance and Transparency in Health Care identified gaps in the in-patient care of elderly patients related to the prevention, screening and treatment of POD, as required by consensus-based and evidence-based delirium guidelines. This paper introduces the QC-POD protocol, which aims to implement these guidelines into the clinical routine. There is an urgent need for well-structured, standardised and interdisciplinary pathways that enable the reliable screening and treatment of POD. Along with effective preventive measures, these concepts have a considerable potential to improve the care of elderly patients. Methods and analysis The QC-POD study is a non-randomised, pre–post, monocentric, prospective trial with an interventional concept following a baseline control period. The QC-POD trial was initiated on 1 April 2020 between Charité-Universitätsmedizin Berlin and the German health insurance company BARMER and will end on 30 June 2023. Inclusion criteria: patients 70 years of age or older that are scheduled for a surgical procedure requiring anaesthesia and insurance with the QC partner (BARMER). Exclusion criteria included patients with a language barrier, moribund patients and those unwilling or unable to provide informed consent. The QC-POD protocol provides perioperative intervention at least two times per day, with delirium screening and non-pharmacological preventive measures. Ethics and dissemination This protocol was approved by the ethics committee of the Charité-Universitätsmedizin, Berlin, Germany (EA1/054/20). The results will be published in a peer-reviewed scientific journal and presented at national and international conferences