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Retinitis pigmentosa (RP), an inherited retinal disease, affects 1,5 million people worldwide. The initial mutation-driven photoreceptor degeneration leads to chronic inflammation, characterized by Müller cell activation and upregulation of CD44. CD44 is a cell surface transmembrane glycoprotein and the primary receptor for hyaluronic acid. It is involved in many pathological processes, but little is known about CD44's retinal functions. CD44 expression is also increased in Müller cells from our Pde6bSTOP/STOP RP mouse model. To gain a more detailed understanding of CD44's role in healthy and diseased retinas, we analyzed Cd44-/- and Cd44-/-Pde6bSTOP/STOP mice, respectively. The loss of CD44 led to enhanced photoreceptor degeneration, reduced retinal function, and increased inflammatory response. To understand the underlying mechanism, we performed proteomic analysis on isolated Müller cells from Cd44-/- and Cd44-/-Pde6bSTOP/STOP retinas and identified a significant downregulation of glutamate transporter 1 (SLC1A2). This downregulation was accompanied by higher glutamate levels, suggesting impaired glutamate homeostasis. These novel findings indicate that CD44 stimulates glutamate uptake via SLC1A2 in Müller cells, which in turn, supports photoreceptor survival and function.
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Células Ependimogliais , Receptores de Hialuronatos , Retinose Pigmentar , Transdução de Sinais , Animais , Receptores de Hialuronatos/metabolismo , Receptores de Hialuronatos/genética , Camundongos , Células Ependimogliais/metabolismo , Transdução de Sinais/fisiologia , Retinose Pigmentar/metabolismo , Retinose Pigmentar/patologia , Retinose Pigmentar/genética , Camundongos Knockout , Camundongos Endogâmicos C57BL , Células Fotorreceptoras de Vertebrados/metabolismo , Sobrevivência Celular/fisiologia , Camundongos Transgênicos , Retina/metabolismo , Retina/patologiaRESUMO
OBJECTIVE: Retinitis pigmentosa (RP) is a hereditary retinal disease characterized by progressive photoreceptor degeneration, leading to vision loss. The best hope for a cure for RP lies in gene therapy. However, given that RP patients are most often diagnosed in the midst of ongoing photoreceptor degeneration, it is unknown how the retinal proteome changes as RP disease progresses, and which changes can be prevented, halted, or reversed by gene therapy. METHODS: Here, we used a Pde6b-deficient RP gene therapy mouse model and performed untargeted proteomic analysis to identify changes in protein expression during degeneration and after treatment. RESULTS: We demonstrated that Pde6b gene restoration led to a novel form of homeostatic plasticity in rod phototransduction which functionally compensates for the decreased number of rods. By profiling protein levels of metabolic genes and measuring metabolites, we observed an upregulation of proteins associated with oxidative phosphorylation in mutant and treated photoreceptors. CONCLUSION: In conclusion, the metabolic demands of the retina differ in our Pde6b-deficient RP mouse model and are not rescued by gene therapy treatment. These findings provide novel insights into features of both RP disease progression and long-term rescue with gene therapy.
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BACKGROUND: Postoperative delirium (POD) following surgery is a prevalent and distressing condition associated with adverse patient outcomes and an increased healthcare burden. OBJECTIVES: To assess the effectiveness of the Safe Brain Initiative care bundle (SBI-CB) in reducing POD in the postanesthesia care unit (PACU). DESIGN: A multicenter, quality-improvement initiative with retrospective analysis of collected data. SETTING: The study was conducted in the operating rooms and postanesthesia care units (PACUs) of four hospitals across Denmark and Turkey. PATIENTS: The convenience sample of patients were aged ≥18 years, scheduled for surgery, and could communicate verbally. Age, sex, preoperative delirium, and the American Society for Anesthesiology physical status classification were used in statistical methods to control for potential confounding influences. INTERVENTION: The SBI-CB, 18 delirium-reducing recommendations aligned with international guidelines. The intervention included patient education, staff training, coordination meetings across centers, and a dashboard for the monitoring of outcomes in the PACU. MAIN OUTCOME MEASURES: The primary outcome was the POD trend in the PACU during implementation months, assessed through Nu-DESC screening at up to three time points in the PACU. We also examined the length of hospital stay. RESULTS: Data were collected from 18,697 adult patients across four hospitals. Initial POD incidence in the PACU after the first three months was 16.36% across all sites (n = 1021). POD in the PACU was observed across all age groups, with peak incidence in younger (18-35 years) and older (>75 years) patients. General anesthesia and longer surgical duration (>1 h) were identified as significant risk factors for POD in the PACU. Matched patients who experienced POD in the PACU had longer stays in hospital, with a mean increase from 35 to 69 h (p < 0.001). Implementation of the SBI-CB was associated with a decreased risk of POD in the PACU for each month of SBI-CB implementation (adjusted odds ratio 0.96, 95% confidence interval: [0.94, 0.97], p < 0.001). CONCLUSIONS: The presented pragmatic implementation of a multidisciplinary care bundle, encompassing pre-, intra-, and postoperative measures alongside outcome monitoring, has the potential to significantly reduce the incidence of POD in the PACU. Improved patient outcomes may be achieved for general surgical departments with patient cohorts not typically considered at risk for developing POD. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT05765162.
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Postoperative delirium (POD) remains a common, dangerous and resource-consuming adverse event but is often preventable. The whole peri-operative team can play a key role in its management. This update to the 2017 ESAIC Guideline on the prevention of POD is evidence-based and consensus-based and considers the literature between 01 April 2015, and 28 February 2022. The search terms of the broad literature search were identical to those used in the first version of the guideline published in 2017. POD was defined in accordance with the DSM-5 criteria. POD had to be measured with a validated POD screening tool, at least once per day for at least 3 days starting in the recovery room or postanaesthesia care unit on the day of surgery or, at latest, on postoperative day 1. Recent literature confirmed the pathogenic role of surgery-induced inflammation, and this concept reinforces the positive role of multicomponent strategies aimed to reduce the surgical stress response. Although some putative precipitating risk factors are not modifiable (length of surgery, surgical site), others (such as depth of anaesthesia, appropriate analgesia and haemodynamic stability) are under the control of the anaesthesiologists. Multicomponent preoperative, intra-operative and postoperative preventive measures showed potential to reduce the incidence and duration of POD, confirming the pivotal role of a comprehensive and team-based approach to improve patients' clinical and functional status.
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Humanos , Adulto , Cuidados Pós-Operatórios/normas , Delírio do Despertar/prevenção & controleRESUMO
Circulating endothelial cells (CEC) are arising as biomarkers for vascular diseases. However, whether they can be utilized as markers of endothelial cell (EC) senescence in vivo remains unknown. Here, we present a protocol to isolate circulating endothelial cells for a characterization of their senescent signature. Further, we characterize different models of EC senescence induction in vitro and show similar patterns of senescence being upregulated in CECs of aged patients as compared to young volunteers. Replication-(ageing), etoposide-(DNA damage) and angiotensin II-(ROS) induced senescence models showed the expected cell morphology and proliferation-reduction effects. Expression of senescence-associated secretory phenotype markers was specifically upregulated in replication-induced EC senescence. All models showed reduced telomere lengths and induction of the INK4a/ARF locus. Additional p14ARF-p21 pathway activation was observed in replication- and etoposide-induced EC senescence. Next, we established a combined magnetic activated- and fluorescence activated cell sorting (MACS-FACS) based protocol for CEC isolation. Interestingly, CECs isolated from aged volunteers showed similar senescence marker patterns as replication- and etoposide-induced senescence models. Here, we provide first proof of senescence in human blood derived circulating endothelial cells. These results hint towards an exciting future of using CECs as mirror cells for in vivo endothelial cell senescence, of particular interest in the context of endothelial dysfunction and cardiovascular diseases.
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Células Endoteliais , Doenças Vasculares , Humanos , Idoso , Células Endoteliais/metabolismo , Etoposídeo/farmacologia , Senescência Celular , Envelhecimento , Doenças Vasculares/metabolismoRESUMO
Diabetic retinopathy (DR) is considered a primarily microvascular complication of diabetes. Müller glia cells are at the centre of the retinal neurovascular unit and play a critical role in DR. We therefore investigated Müller cell-specific signalling pathways that are altered in DR to identify novel targets for gene therapy. Using a multi-omics approach on purified Müller cells from diabetic db/db mice, we found the mRNA and protein expression of the glucocorticoid receptor (GR) to be significantly decreased, while its target gene cluster was down-regulated. Further, oPOSSUM TF analysis and ATAC- sequencing identified the GR as a master regulator of Müller cell response to diabetic conditions. Cortisol not only increased GR phosphorylation. It also induced changes in the expression of known GR target genes in retinal explants. Finally, retinal functionality was improved by AAV-mediated overexpression of GR in Müller cells. Our study demonstrates an important role of the glial GR in DR and implies that therapeutic approaches targeting this signalling pathway should be aimed at increasing GR expression rather than the addition of more ligand.
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Diabetes Mellitus , Retinopatia Diabética , Animais , Camundongos , Diabetes Mellitus/metabolismo , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Células Ependimogliais/metabolismo , Neuroglia/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Retina/metabolismoRESUMO
BACKGROUND: Postoperative delirium is a common complication in elderly patients undergoing anesthesia. Even though it is increasingly recognized as an important health issue, the early detection of patients at risk for postoperative delirium remains a challenge. This study aims to identify predictors of postoperative delirium by analyzing frontal electroencephalogram at propofol-induced loss of consciousness. METHODS: This prospective, observational single-center study included patients older than 70 yr undergoing general anesthesia for a planned surgery. Frontal electroencephalogram was recorded on the day before surgery (baseline) and during anesthesia induction (1, 2, and 15 min after loss of consciousness). Postoperative patients were screened for postoperative delirium twice daily for 5 days. Spectral analysis was performed using the multitaper method. The electroencephalogram spectrum was decomposed in periodic and aperiodic (correlates to asynchronous spectrum wide activity) components. The aperiodic component is characterized by its offset (y intercept) and exponent (the slope of the curve). Computed electroencephalogram parameters were compared between patients who developed postoperative delirium and those who did not. Significant electroencephalogram parameters were included in a binary logistic regression analysis to predict vulnerability for postoperative delirium. RESULTS: Of 151 patients, 50 (33%) developed postoperative delirium. At 1 min after loss of consciousness, postoperative delirium patients demonstrated decreased alpha (postoperative delirium: 0.3 µV2 [0.21 to 0.71], no postoperative delirium: 0.55 µV2 [0.36 to 0.74]; P = 0.019] and beta band power [postoperative delirium: 0.27 µV2 [0.12 to 0.38], no postoperative delirium: 0.38 µV2 [0.25 to 0.48]; P = 0.003) and lower spectral edge frequency (postoperative delirium: 10.45 Hz [5.65 to 15.04], no postoperative delirium: 14.56 Hz [9.51 to 16.65]; P = 0.01). At 15 min after loss of consciousness, postoperative delirium patients displayed a decreased aperiodic offset (postoperative delirium: 0.42 µV2 (0.11 to 0.69), no postoperative delirium: 0.62 µV2 [0.37 to 0.79]; P = 0.004). The logistic regression model predicting postoperative delirium vulnerability demonstrated an area under the curve of 0.73 (0.69 to 0.75). CONCLUSIONS: The findings suggest that electroencephalogram markers obtained during loss of consciousness at anesthesia induction may serve as electroencephalogram-based biomarkers to identify at an early time patients at risk of developing postoperative delirium.
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Delírio , Delírio do Despertar , Humanos , Idoso , Delírio do Despertar/etiologia , Delírio/diagnóstico , Estudos Prospectivos , Eletroencefalografia , Anestesia Geral/efeitos adversos , Inconsciência , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
Climate change is a defining issue for our generation. The carbon footprint of clinical practice accounts for 4.7% of European greenhouse gas emissions, with the European Union ranking as the third largest contributor to the global healthcare industry's carbon footprint, after the United States and China. Recognising the importance of urgent action, the European Society of Anaesthesiology and Intensive Care (ESAIC) adopted the Glasgow Declaration on Environmental Sustainability in June 2023. Building on this initiative, the ESAIC Sustainability Committee now presents a consensus document in perioperative sustainability. Acknowledging wider dimensions of sustainability, beyond the environmental one, the document recognizes healthcare professionals as cornerstones for sustainable care, and puts forward recommendations in four main areas: direct emissions, energy, supply chain and waste management, and psychological and self-care of healthcare professionals. Given the urgent need to cut global carbon emissions, and the scarcity of evidence-based literature on perioperative sustainability, our methodology is based on expert opinion recommendations. A total of 90 recommendations were drafted by 13 sustainability experts in anaesthesia in March 2023, then validated by 36 experts from 24 different countries in a two-step Delphi validation process in May and June 2023. To accommodate different possibilities for action in high- versus middle-income countries, an 80% agreement threshold was set to ease implementation of the recommendations Europe-wide. All recommendations surpassed the 80% agreement threshold in the first Delphi round, and 88 recommendations achieved an agreement >90% in the second round. Recommendations include the use of very low fresh gas flow, choice of anaesthetic drug, energy and water preserving measures, "5R" policies including choice of plastics and their disposal, and recommendations to keep a healthy work environment or on the importance of fatigue in clinical practice. Executive summaries of recommendations in areas 1, 2 and 3 are available as cognitive aids that can be made available for quick reference in the operating room.
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Anestesia , Anestesiologia , Humanos , Consenso , China , Cuidados CríticosRESUMO
BACKGROUND: Psychotic disorders are highly heritable, yet the evidence is less clear for subclinical psychosis expression, such as psychotic experiences (PEs). We examined if PEs in parents were associated with PEs in offspring. METHODS: As part of the Danish general population Lolland-Falster Health Study, families with youths aged 11-17 years were included. Both children and parents reported PEs according to the Psychotic Like Experiences Questionnaire, counting only 'definite' PEs. Parents additionally reported depressive symptoms, anxiety, and mental wellbeing. The associations between parental and child PEs were estimated using generalized estimating equations with an exchangeable correlation structure to account for the clustering of observations within families, adjusting for sociodemographic characteristics. RESULTS: Altogether, 984 youths (mean age 14.3 years [s.d. 2.0]), 700 mothers, and 496 fathers from 766 households completed PEs-questionnaires. Offspring of parents with PEs were at an increased risk of reporting PEs themselves (mothers: adjusted risk ratio (aRR) 2.42, 95% CI 1.73-3.38; fathers: aRR 2.25, 95% CI 1.42-3.59). Other maternal problems (depression, anxiety, and poor mental well-being), but not paternal problems, were also associated with offspring PEs. In multivariate models adjusting for parental problems, PEs, but not other parental problems, were robustly associated with offspring PEs (mothers: aRR 2.25, 95% CI 1.60-3.19; fathers: aRR 2.44, 95% CI 1.50-3.96). CONCLUSIONS: The current findings add novel evidence suggesting that specific psychosis vulnerability in families is expressed at the lower end of the psychosis continuum, underlining the importance of assessing youths' needs based on psychosis vulnerability broadly within the family systems.
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Transtornos Psicóticos , Masculino , Feminino , Criança , Adolescente , Humanos , Estudos de Coortes , Transtornos Psicóticos/epidemiologia , Pai , Mães , PaisRESUMO
Postoperative delirium (POD) remains a common, dangerous and resource-consuming adverse event but is often preventable. The whole peri-operative team can play a key role in its management. This update to the 2017 ESAIC Guideline on the prevention of POD is evidence-based and consensus-based and considers the literature between 01 April 2015, and 28 February 2022. The search terms of the broad literature search were identical to those used in the first version of the guideline published in 2017. POD was defined in accordance with the DSM-5 criteria. POD had to be measured with a validated POD screening tool, at least once per day for at least 3 days starting in the recovery room or postanaesthesia care unit on the day of surgery or, at latest, on postoperative day 1. Recent literature confirmed the pathogenic role of surgery-induced inflammation, and this concept reinforces the positive role of multicomponent strategies aimed to reduce the surgical stress response. Although some putative precipitating risk factors are not modifiable (length of surgery, surgical site), others (such as depth of anaesthesia, appropriate analgesia and haemodynamic stability) are under the control of the anaesthesiologists. Multicomponent preoperative, intra-operative and postoperative preventive measures showed potential to reduce the incidence and duration of POD, confirming the pivotal role of a comprehensive and team-based approach to improve patients' clinical and functional status.
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Anestesiologia , Delírio , Delírio do Despertar , Adulto , Humanos , Delírio do Despertar/diagnóstico , Delírio do Despertar/epidemiologia , Delírio do Despertar/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Consenso , Cuidados Críticos , Fatores de RiscoRESUMO
In retinal degenerative diseases, such as retinitis pigmentosa (RP), the characteristic photoreceptor cell death is associated with changes of microglia and macroglia cells. Gene therapy, a promising treatment option for RP, is based on the premise that glial cell remodeling does not impact vision rescue. However, the dynamics of glial cells after treatment at late disease stages are not well understood. Here, we tested the reversibility of specific RP glia phenotypes in a Pde6b-deficient RP gene therapy mouse model. We demonstrated an increased number of activated microglia, retraction of microglial processes, reactive gliosis of Müller cells, astrocyte remodelling and an upregulation of glial fibrillary acidic protein (GFAP) in response to photoreceptor degeneration. Importantly, these changes returned to normal following rod rescue at late disease stages. These results suggest that therapeutic approaches restore the homeostasis between photoreceptors and glial cells.
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Degeneração Retiniana , Retinose Pigmentar , Animais , Camundongos , Microglia/metabolismo , Retinose Pigmentar/terapia , Retina/metabolismo , Neuroglia/metabolismo , Degeneração Retiniana/genética , Degeneração Retiniana/metabolismo , Modelos Animais de DoençasRESUMO
Purpose: Retinitis pigmentosa (RP) is the most common cause of inherited blindness, with onset occurring as early as 4 years of age in certain rare but severe forms caused by mutations in the gamma subunit of phosphodiesterase 6 (PDE6). Studies in humans and mice have shown that RP pathology begins with progressive photoreceptor death, which then drives changes in downstream neurons, neighboring retinal pigment epithelium (RPE), and vasculature. Here, we present the first detailed analysis of RP disease progression in Pde6g-deficient mice. Design: Experimental study of an RP mouse model. Subjects: We studied Pde6g-/- and Pde6g+/- mice at the age of 7, 16, 30, 44, and 56 days with n = 2 to 5 per group and time point. Methods: Photoreceptor degeneration and retinal remodeling were analyzed in retinal sections by immunofluorescence. Retinal blood vessel degradation was analyzed in flat-mounted retinas immunolabeled for isolectin GS-IB4. Protein expression was measured by immunoblot. Acellular capillaries were assessed in trypsin-digested and hematoxylin-eosin-stained retinas at postnatal day (P) 44. Retinal pigment epithelium cells were delineated in flat-mounted RPE-choroid-sclera by immunolabeling for the cell-adhesion protein ß-catenin. Main Outcome Measures: Immunofluorescence and morphometry (quantitative analysis of outer nuclear layer, dendrite area, vessel area, acellular vessels, RPE cell size, number of nuclei per RPE cell, RPE cell eccentricity, and RPE cell solidity). Results: This novel RP model exhibits early onset and rapid rod degeneration, with the vast majority gone by P16. This pathology leads to retinal remodeling, including changes of inner retinal neurons, early activation of glia cells, degradation of retinal vasculature, and structural abnormalities of the RPE. Conclusions: The pathology in our Pde6g-/- mouse model precisely mirrors human RP progression. The results demonstrate the significant role of the gamma subunit in maintaining phosphodiesterase activity and provide new insights into the disease progression due to Pde6g deficiency. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.
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OBJECTIVE: The objective of this study was to investigate the predictive value of sex, age, body mass index (BMI), Eating Disorder Examination (EDE) score, social risk factors, and psychiatric comorbidities for hospitalization and hospitalization duration among children and adolescents suffering from eating disorders. METHOD: This prospective cohort study involved 522 consecutive patients who had been referred to a specialized eating disorder unit between January 1, 2009 and December 31, 2015; participants were followed up until August 1, 2016 by medical records. We used regression analyses to evaluate the prognostic value of sex, age, BMI, EDE, eating disorder diagnoses, social risk factors, and psychiatric comorbidities concerning inpatient hospitalization and hospitalization duration. RESULTS: We found that younger age, higher EDE global score, lower BMI percentile, anorexia nervosa, a higher number of social risk factors, and the presence of diagnosed self-harm increased the odds of being hospitalized, while being female and having a comorbid autism spectrum condition increased the duration of hospitalization. No other psychiatric comorbidity was found to significantly predict hospitalization or duration of hospitalization. DISCUSSION: The odds of being hospitalized were predicted by the severity of anorexia nervosa and indicators of social risk factors in the family, whereas the duration of hospitalization was predicted by having a comorbid autism spectrum condition, indicating a difference between the factors affecting the risk of hospitalization and the factors affecting the duration of hospitalization. This calls for further exploration of tailored treatments for eating disorders. PUBLIC SIGNIFICANCE STATEMENT: This study finds that hospitalization for an eating disorder is predicted by the severity of the illness, self-harm, and social risk factors. Duration of hospitalization is predicted by having a comorbid autism spectrum condition. These findings indicate that the treatment of eating disorders may require different treatment approaches depending on the presentation of the individual patient to reduce both the need for hospitalization and the length of inpatient stay.
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Anorexia Nervosa , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Adolescente , Feminino , Criança , Masculino , Estudos Prospectivos , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Hospitalização , Anorexia Nervosa/diagnóstico , Anorexia Nervosa/epidemiologia , Anorexia Nervosa/terapia , Comorbidade , Índice de Massa CorporalRESUMO
Ongoing high consumption of resources results in exceeding the planetary boundaries. Modern healthcare systems contribute to this problem. To address this issue, this article provides an overview of various aspects of sustainable actions in medical offices and clinics that can also be applied to dermatology. Specific fields of action include energy consumption, structural measures, traffic and mobility, organization including digitalization as well as personnel and evaluation. Moreover, we discuss specific topics such as hygiene and cleansing, dermatosurgery and prescription practices. External treatments and cosmetics are discussed separately as dermatological peculiarities. Finally, we provide information on established initiatives for more sustainable health care in Germany. We aim to encourage critical reappraisal of currently established practices and to stimulate the implementation of sustainable measures.
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Dermatologia , Desenvolvimento Sustentável , Humanos , Alemanha , Dermatologia/organização & administraçãoRESUMO
Background: Postoperative Delirium (POD) is the most frequent neurocognitive complication after general anesthesia in older patients. The development of POD is associated with prolonged periods of burst suppression activity in the intraoperative electroencephalogram (EEG). The risk to present burst suppression activity depends not only on the age of the patient but is also more frequent during propofol anesthesia as compared to inhalative anesthesia. The aim of our study is to determine, if the risk to develop POD differs depending on the anesthetic agent given and if this correlates with a longer duration of intraoperative burst suppression. Methods: In this secondary analysis of the SuDoCo trail [ISRCTN 36437985] 1277 patients, older than 60 years undergoing general anesthesia were included. We preprocessed and analyzed the raw EEG files from each patient and evaluated the intraoperative burst suppression duration. In a logistic regression analysis, we assessed the impact of burst suppression duration and anesthetic agent used for maintenance on the risk to develop POD. Results: 18.7% of patients developed POD. Burst suppression duration was prolonged in POD patients (POD 27.5 min ± 21.3 min vs. NoPOD 21.4 ± 16.2 min, p < 0.001), for each minute of prolonged intraoperative burst suppression activity the risk to develop POD increased by 1.1% (OR 1.011, CI 95% 1.000-1.022, p = 0.046). Burst suppression duration was prolonged under propofol anesthesia as compared to sevoflurane and desflurane anesthesia (propofol 32.5 ± 20.3 min, sevoflurane 17.1 ± 12.6 min and desflurane 20.1 ± 16.0 min, p < 0.001). However, patients receiving desflurane anesthesia had a 1.8fold higher risk to develop POD, as compared to propofol anesthesia (OR 1.766, CI 95% 1.049-2.974, p = 0.032). Conclusion: We found a significantly increased risk to develop POD after desflurane anesthesia in older patients, even though burst suppression duration was shorter under desflurane anesthesia as compared to propofol anesthesia. Our finding might help to explain some discrepancies in studies analyzing the impact of burst suppression duration and EEG-guided anesthesia on the risk to develop POD.
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Objective: In older patients receiving general anesthesia, postoperative delirium (POD) is the most frequent form of cerebral dysfunction. Early identification of patients at higher risk to develop POD could provide the opportunity to adapt intraoperative and postoperative therapy. We, therefore, propose a machine learning approach to predict the risk of POD in elderly patients, using routine intraoperative electroencephalography (EEG) and clinical data that are readily available in the operating room. Methods: We conducted a retrospective analysis of the data of a single-center study at the Charité-Universitätsmedizin Berlin, Department of Anesthesiology [ISRCTN 36437985], including 1,277 patients, older than 60 years with planned surgery and general anesthesia. To deal with the class imbalance, we used balanced ensemble methods, specifically Bagging and Random Forests and as a performance measure, the area under the ROC curve (AUC-ROC). We trained our models including basic clinical parameters and intraoperative EEG features in particular classical spectral and burst suppression signatures as well as multi-band covariance matrices, which were classified, taking advantage of the geometry of a Riemannian manifold. The models were validated with 10 repeats of a 10-fold cross-validation. Results: Including EEG data in the classification resulted in a robust and reliable risk evaluation for POD. The clinical parameters alone achieved an AUC-ROC score of 0.75. Including EEG signatures improved the classification when the patients were grouped by anesthetic agents and evaluated separately for each group. The spectral features alone showed an AUC-ROC score of 0.66; the covariance features showed an AUC-ROC score of 0.68. The AUC-ROC scores of EEG features relative to patient data differed by anesthetic group. The best performance was reached, combining both the EEG features and the clinical parameters. Overall, the AUC-ROC score was 0.77, for patients receiving Propofol it was 0.78, for those receiving Sevoflurane it was 0.8 and for those receiving Desflurane 0.73. Applying the trained prediction model to an independent data set of a different clinical study confirmed these results for the combined classification, while the classifier on clinical parameters alone did not generalize. Conclusion: A machine learning approach combining intraoperative frontal EEG signatures with clinical parameters could be an easily applicable tool to early identify patients at risk to develop POD.
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The electrochemical reduction of CO2 is a pivotal technology for the defossilization of the chemical industry. Although pilot-scale electrolyzers exist, water management and salt precipitation remain a major hurdle to long-term operation. In this work, we present high-resolution neutron imaging (6 µm) of a zero-gap CO2 electrolyzer to uncover water distribution and salt precipitation under application-relevant operating conditions (200 mA cm-2 at a cell voltage of 2.8 V with a Faraday efficiency for CO of 99%). Precipitated salts penetrating the cathode gas diffusion layer can be observed, which are believed to block the CO2 gas transport and are therefore the major cause for the commonly observed decay in Faraday efficiency. Neutron imaging further shows higher salt accumulation under the cathode channel of the flow field compared to the land.