Mitochondria are morphologically and functionally heterogeneous and dynamically adapt to the current metabolic status of their hosting cell. Moreover, they are prominent sources but also sensitive targets of redox modulation and oxidative stress. Such subcellular ROS/redox signals are considered pivotal aspects in health and disease. Yet, their deciphering requires advanced optical tools. Here we took advantage of transgenic redoxindicator mice expressing a mitochondria-targeted reduction/oxidation-sensitive green fluorescent protein (roGFPm) in excitatory projection neurons. By excitation-ratiometric two-photon microscopy we quantified in acute brain slices the redox conditions of individual mitochondria. After developing adequate redox sensor calibrations and solving laser-mediated bleaching issues, we finally chose caudoputamen, which showed the most promising mitochondrial arrangement for our imaging approach. Confirming the reliability of singlemitochondria redox imaging, we characterized the interplay of redox state and mitochondrial morphology. In general, roGFPm was more oxidized in spherical than in filamentous mitochondria. Acute hypoxia reverted mitochondria to a more roundish shape and evoked a reducing shift. Furthermore, the fraction of spherical mitochondria increased with aging. Around postnatal day (pd)350, a significantly higher fraction of roundish mitochondria was present in females than in males. In addition, from pd150 on, female mice showed lower degrees of roGFPm oxidation than males. Both findings might be linked to estrogen levels, which decrease in female mice with reproductive senescence around pd350. In view of the pivotal role of mitochondria for cellular wellbeing and their involvement in various neuropathologies, the established single-organelle redox-imaging approach will foster further detailed studies.

Rett syndrome (RTT) is associated with a systemic redox imbalance, potentially provoking cellular dysfunction and contributing to some of the disease symptoms. While previous studies have reported these redox alterations also in brain, the exact cerebral redox pattern remains unclear. We therefore generated MeCP2-deficient mice expressing the cytosolic redox sensor roGFPc in excitatory projection neurons. Taking advantage of the earlier developed excitation ratiometric 2-photon imaging, we mapped the redox conditions of individual hippocampal and cortical neurons in acute brain tissue slices of female mice. These quantitative redox analyses revealed clear brain-regional differences in the degree of roGFPc oxidation, with dentate gyrus and CA3 being most oxidized, CA1 being least oxidized and cortical areas presenting intermediate oxidation levels. On postnatal day p50, hardly any RTT-related differences were evident. With maturation (>p100), redox conditions became more reducing in WT females. This was, however, not the case in MeCP2-deficient females, whose hippocampal and especially cortical neurons now appeared clearly more oxidized. By correlative redox microscopy, we succeeded to relate cellular redox-conditions to cellular MeCP2 expression. Validation in CA1 and somatosensory cortex revealed that, based on improved discrimination sensitivity, a more oxidized redox balance became detectable in MeCP2-deficient cortical neurons already on p50. Expression of a mitochondrial catalase efficiently abolished the more oxidizing redox milieu in MeCP2-deficient cortical neurons. This confirms a widespread oxidative burden in forebrain neurons, which manifests already in pre-symptomatic MeCP2-deficient female mice and intensifies with disease progression. Stabilizing mitochondrial function by targeted catalase expression proved potentially protective.

Spreading depolarization (SD) causes a massive neuronal/glial depolarization, disturbs ionic homeostasis and deranges neuronal network function. The metabolic burden imposed by SD may also generate marked amounts of reactive oxygen species (ROS). Yet, proper optical tools are required to study this aspect with spatiotemporal detail. Therefore, we earlier generated transgenic redox indicator mice. They express in excitatory projection neurons the cytosolic redox-sensor roGFP, a reduction/oxidation sensitive green fluorescent protein which is ratiometric by excitation and responds reversibly to redox alterations. Using adult male roGFPc mice, we analyzed SD-related ROS production in CA1 stratum pyramidale of submerged slices. SD was induced by K+ microinjection, O2 withdrawal or mitochondrial uncoupling (FCCP). The extracellular DC potential deflection was accompanied by a spreading wavefront of roGFP oxidation, confirming marked neuronal ROS generation. Hypoxia-induced SD was preceded by a moderate oxidation, which became intensified as the DC potential deflection occurred. Upon K+-induced SD, roGFP oxidation slowly recovered within 10–15 min in some slices. Upon FCCP-or hypoxia-induced SD, recovery was limited. Withdrawing extracellular Ca2+ markedly dampened the SD-related roGFP oxidation and improved its reversibility, confirming a key-role of neuronal Ca2+ load in SD-related ROS generation. Neither mitochondrial uncoupling, nor inhibition of NADPH oxidase or xanthine oxidase abolished the SD-related roGFP oxidation. Therefore, ROS generation during SD involves mitochondria as well as non-mitochondrial sources. This first-time analysis of SD-related ROS dynamics became possible based on quantitative redox imaging in roGFP mice, an advanced approach, which will contribute to further decipher the molecular understanding of SD in brain pathophysiology.

Background: Postoperative pain influences rehabilitation, postoperative complications and quality of life. Despite its impact, there are no uniform treatment guidelines. Different centers seem to use various strategies. This study aims to analyze pain management regimens used after anatomic VATS resections in Austrian thoracic surgery units, with a special interest in opioid usage and strategies to avoid opioids. Methods: A questionnaire was designed to assess the use of regional anesthesia, postoperative pain medication and characteristics of individual pain management regimens. The questionnaire was sent to all thoracic surgery units in Austria, with nine out of twelve departments returning them. Results: All departments use regional anesthesia during the procedure. Four out of nine centers use epidural analgesia or an intercostal catheter for postoperative regional anesthesia in at least 50% of patients. Two departments follow an opioid restrictive regimen, five depend on the visual analogue scale (VAS) and two administer opioids on a fixed schedule. Three out of nine departments use NSAIDs on a fixed schedule. The most used medication is metamizole (eight out of nine centers; six on a fixed schedule, two depending on VAS) followed by piritramide (six out of nine centers; none as a fixed prescription). Conclusions: This study reflects the heterogeneity in postoperative pain treatment after VATS anatomic lung resections. All departments use some form of regional anesthesia in the perioperative period; prolonged regional anesthesia is not utilized uniformly to reduce opioid consumption, as suggested in enhanced recovery after surgery programs. More evidence is needed to optimize and standardize postoperative pain treatment.

Purpose To evaluate the impact of the iridocorneal angle size (ICAS) on the diurnal intraocular pressure (IOP) in patients with suspected glaucoma (SG). Method Patients with any eye-pressure lowering medication or previous ocular surgery were excluded. In a retrospective study set, diurnal IOP profiles of 120 patients (205 eyes) within a 48-h period were analysed by regression analysis. Of those eyes, 44 were diagnosed to have glaucoma. The remaining eyes were used as healthy control group (HCG). Results The overall mean IOP was 15.63 mmHg ± 2.72 mmHg and mean ICAS was 23.92° ± 4.74°. In the glaucoma cohort, mean IOP was 18.77 ± 1.86 mmHg and mean ICAS was 25.02° ± 4.96°. In the HCG, mean IOP was 14.77 ± 2.25 mmHg and mean ICAS was 23.62° ± 4.64°. In the total cohort, as well as in the subgroups (HCG or glaucoma), regression analysis showed no significant impact even of the minimum ICAS, which was larger than 10°, on average ( P = 0.89), maximum ( P = 0.88), and range of IOP ( P = 0.49) within 48 h. The difference between glaucoma cohort and HCG cohort was significant in terms of IOP ( P < 0.001), but not for minimum ICAS ( P = 0.07). Chi-square test showed no increase in prevalence of IOP peaks of > 21 mmHg within 48 h in eyes with an angle between 10° and 20° ( P = 0.18). Conclusion An ICAS of larger than 10° in HCG or glaucoma patients with an open-angle does not influence the minimum, average, maximum or range of IOP. Additionally, an angle size larger than 10° does not allow the prediction of IOP changes in these two cohorts.

APOE genotype is the most significant genetic risk factor for the development of Alzheimer’s disease, with 40-60% of Alzheimer’s patients carrying at least one APOE4 allele. In addition to its pleiotropic effects on ageing and the brain, recent evidence suggests that APOE genotype may also affect the gut microbiome structure and function. Dietary polyphenols - bioactive molecules found in fruits and vegetables - have been reported to slow cognitive decline and to affect gut microbiota speciation and metabolism. However, differences in the metabolism of these bioactive compounds according to APOE genotypes have not been previously explored. To address this knowledge gap, we ran an animal study using APOE3 and APOE4 targeted replacement (TR) mice. Animals were fed on a low-fat diet (10 kcal% from fat), a high-fat diet (45 kcal% from fat) or a high-fat diet supplemented with a flavan-3-ols rich cocoa extract (100 mg/kg body weight) for 16 weeks. This model has been widely used as a physiologically relevant model for age-related neuroinflammation and cognitive decline in humans, with consistently higher levels in the APOE4-TR vs. APOE3-TR mice, particularly if fed a “western type‟ high fat diet. Significant shifts in microbiome beta diversity were observed in APOE3-TR mice only under a high fat diet, with these mice acquiring an APOE4-TR-like phenotype. Addition of flavan-3-ol rich cocoa reversed this shift by increasing rc4_4, Prevotella, Aldercreutzia and Faecalibacterium genera (log LDA score >2; FDR p-adjusted 0.1) in APOE3-TR mice. Surprisingly, flavan-3-ol rich cocoa did not affect the structure of the APOE 4 mice’s microbiome. Such results were paralleled by an increased urinary excretion of the colon flora-derived flavan-3-ol metabolites 5-(3’,4’-dihydroxyohenyl)-γ-valerolactone (p<0.05), 5-(hydroxyphenyl)valeric acid-4-sulfate (p<0.01) and 4-hydroxy-5-(hydroxyphenyl)valeric acid sulfate (p<0.01) in APOE4-TR mice. These preliminary findings were further validated in a human cohort study (COMBAT Study; NCT03679533) following 12-week consumption of flavan-3-ols rich cranberries. The relationship between polyphenols intake and APOE genotype is intriguing, and further work is required to gain a better understanding of the physiological and molecular mechanisms underlying such disparity between the genotypes.

Rett syndrome (RTT) is a genetic neurodevelopmental disorder with mutations in the X-chromosomal MECP2 (methyl-CpG-binding protein 2) gene. Most patients are young girls. For 7-18 months after birth, they hardly present any symptoms; later they develop mental problems, a lack of communication, irregular sleep and breathing, motor dysfunction, hand stereotypies, and seizures. The complex pathology involves mitochondrial structure and function. Mecp2-/y hippocampal astrocytes show increased mitochondrial contents. Neurons and glia suffer from oxidative stress, a lack of ATP, and increased hypoxia vulnerability. This spectrum of changes demands comprehensive molecular studies of mitochondria to further define their pathogenic role in RTT. Therefore, we applied a comparative proteomic approach for the first time to study the entity of mitochondrial proteins in a mouse model of RTT. In the neocortex and hippocampus of symptomatic male mice, two-dimensional gel electrophoresis and subsequent mass-spectrometry identified various differentially expressed mitochondrial proteins, including components of respiratory chain complexes I and III and the ATP-synthase FoF1 complex. The NADH-ubiquinone oxidoreductase 75 kDa subunit, NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, NADH dehydrogenase [ubiquinone] flavoprotein 2, cytochrome b-c1 complex subunit 1, and ATP synthase subunit d are upregulated either in the hippocampus alone or both the hippocampus and neocortex of Mecp2-/y mice. Furthermore, the regulatory mitochondrial proteins mitofusin-1, HSP60, and 14-3-3 protein theta are decreased in the Mecp2-/y neocortex. The expressional changes identified provide further details of the altered mitochondrial function and morphology in RTT. They emphasize brain-region-specific alterations of the mitochondrial proteome and support the notion of a metabolic component of this devastating disorder.

Background When a patient arrives in the emergency department following a stroke, a traumatic brain injury, or sudden cardiac arrest, there is no therapeutic drug available to help protect their jeopardized neurons. One crucial reason is that we have not identified the molecular mechanisms leading to electrical failure, neuronal swelling, and blood vessel constriction in newly injured gray matter. All three result from a process termed spreading depolarization (SD). Because we only partially understand SD, we lack molecular targets and biomarkers to help neurons survive after losing their blood flow and then undergoing recurrent SD. Methods In this review, we introduce SD as a single or recurring event, generated in gray matter following lost blood flow, which compromises the Na + /K + pump. Electrical recovery from each SD event requires so much energy that neurons often die over minutes and hours following initial injury, independent of extracellular glutamate. Results We discuss how SD has been investigated with various pitfalls in numerous experimental preparations, how overtaxing the Na + /K + ATPase elicits SD. Elevated K + or glutamate are unlikely natural activators of SD. We then turn to the properties of SD itself, focusing on its initiation and propagation as well as on computer modeling. Conclusions Finally, we summarize points of consensus and contention among the authors as well as where SD research may be heading. In an accompanying review, we critique the role of the glutamate excitotoxicity theory, how it has shaped SD research, and its questionable importance to the study of early brain injury as compared with SD theory.

Rett syndrome (RTT) is a severe neurodevelopmental disorder that typically arises from spontaneous germline mutations in the X-chromosomal methyl-CpG binding protein 2 (MECP2) gene. For the first 6–18 months of life, the development of the mostly female patients appears normal. Subsequently, cognitive impairment, motor disturbances, hand stereotypies, epilepsy, and irregular breathing manifest, with previously learned skills being lost. Early mitochondrial impairment and a systemic oxidative burden are part of the complex pathogenesis, and contribute to disease progression. Accordingly, partial therapeutic merits of redox-stabilizing and antioxidant (AO) treatments were reported in RTT patients and Mecp2-mutant mice. Pursuing these findings, we conducted a full preclinical trial on male and female mice to define the therapeutic value of an orally administered AO cocktail composed of vitamin E, N-acetylcysteine, and α-lipoic acid. AO treatment ameliorated some of the microcephaly-related aspects. Moreover, the reduced growth, lowered blood glucose levels, and the hippocampal synaptic plasticity of Mecp2−/y mice improved. However, the first-time detected intensified oxidative DNA damage in Mecp2-mutant cortex persisted. The behavioral performance, breathing regularity, and life expectancy of Mecp2-mutant mice did not improve upon AO treatment. Long-term-treated Mecp2+/− mice eventually became obese. In conclusion, the AO cocktail ameliorated a subset of symptoms of the complex RTT-related phenotype, thereby further confirming the potential merits of AO-based pharmacotherapies. Yet, it also became evident that long-term AO treatment may lose efficacy and even aggravate the metabolic disturbances in RTT. This emphasizes the importance of a constantly well-balanced redox balance for systemic well-being.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief and Authors. Professor Michael Müller approached the journal explaining that he had encountered an issue in the way the spectrofluorometric data analyses was performed. The normalization of the fluorescence curves to their respective starting points (as explained in Figure 1A) overestimated the changes in Mecp2-mutant mice, which usually started at lower levels. This overestimation applies to Figure 3 A-D as well as Table 2 and Table 3 and altered the outcomes of the study. Both the EiC and the authors agreed that a corrigendum would not be appropriate due to the change in conclusion and that the paper should therefore be retracted. The authors apologise for any confusion this paper may have resulted in.

PURPOSE:Filler injections for aesthetic purposes are very popular, but can have far-reaching and irreversible consequences. This report describes the course of a patient with devastating complications after glabellar hyaluronic acid injection, their pathomechanism, management and outcome.OBSERVATIONS:A healthy, 43-year-old woman underwent her first hyaluronic acid injection in the glabella and went blind on her left eye immediately thereafter. Massaging of the injection area and observation were performed, before she presented with swelling of the left forehead and upper lid, ptosis, complete ophthalmoplegia and blindness in our hospital. Immediate massaging of the globe and systemic therapy including acetylsalicylic acid, tinzaparin sodium and cortisone was initiated and hyaluronidase injections in the injection area were performed. In the further course, the patient developed necrotic and hemorrhagic skin and mucosal lesions, lagophthalmos, anterior and posterior segment ischemia and globe hypotonia with consecutive globe deformation. In the follow-up of 2.5 months, lid swelling, lagophthalmos and ptosis resolved and keratopathy improved but blindness, skin lesions and strabismus with reduced eye motility were still present and madarosis and early enophthalmos were detected.CONCLUSIONS AND IMPORTANCE:The outcome of ophthalmic artery occlusion after hyaluronic acid filler injection is poor. Sufficient knowledge about facial anatomy, the implementation of filler injections and the management of complications is essential for the practitioner. The patient should be clarified about potential and even rare risks of these procedures.

Purpose: To compare agreement of anterior segment parameter measurements using an intraoperative optical coherence tomography (iOCT) of a femtosecond laser (LenSx) during interface docking to the eye with preoperative Scheimpflug tomography (Pentacam AXL) and swept-source optical coherence tomography (SS-OCT) (IOLMaster 700). Setting: Department of Ophthalmology, Goethe University, Frankfurt, Germany. Design: Retrospective study. Methods: Anterior segment measurements were performed in mydriasis prior to surgery using Scheimpflug tomography and SS-OCT. Postoperatively, iOCT images were analyzed using a modification of the FIJI image-processing program. Outcome measures included external anterior chamber depth (ACD), central corneal thickness (CCT), and central lens thickness (LT). Results: 95 eyes of 66 patients who underwent planned OCT guided femtosecond laser-assisted lens surgery were included. The ACD measured with the iOCT was −0.011 ± 0.126 mm smaller (P = .389) than that with the SS-OCT and −0.059 ± 0.185 mm than with the Scheimpflug tomography (P = .003). The SS-OCT measured a −0.047 ± 0.146 mm smaller ACD than the Scheimpflug tomography (P = .002). The measurements of CCT using the iOCT and the Scheimpflug tomography (−0.705 ± 20.837 μm, P = .742) and the LT measurements using SS-OCT and iOCT (−0.050 ± 0.089 mm, P < .001) showed no clinically relevant difference. Only the ACD between the iOCT and the Scheimpflug tomography showed a clinically relevant difference. Conclusions: The comparison of the anterior segment parameters of iOCT with SS-OCT showed no clinically relevant differences regarding the ACD and the LT. However, Scheimpflug tomography vs iOCT measured a small clinically relevant difference for ACD. The iOCT showed no clinically relevant differences in anterior segment parameters compared with the SS-OCT. A small clinically relevant difference for ACD was found in comparison with that of a Scheimpflug device.

Using unsupervised metabolomics, we defined the complex metabolic conditions in the cortex of a mouse model of Rett syndrome (RTT). RTT, which represents a cause of mental and cognitive disabilities in females, results in profound cognitive impairment with autistic features, motor disabilities, seizures, gastrointestinal problems, and cardiorespiratory irregularities. Typical RTT originates from mutations in the X-chromosomal methyl-CpG-binding-protein-2 (Mecp2) gene, which encodes a transcriptional modulator. It then causes a deregulation of several target genes and metabolic alterations in the nervous system and peripheral organs. We identified 101 significantly deregulated metabolites in the Mecp2-deficient cortex of adult male mice; 68 were increased and 33 were decreased compared to wildtypes. Pathway analysis identified 31 mostly upregulated metabolic pathways, in particular carbohydrate and amino acid metabolism, key metabolic mitochondrial/extramitochondrial pathways, and lipid metabolism. In contrast, neurotransmitter-signaling is dampened. This metabolic fingerprint of the Mecp2-deficient cortex of severely symptomatic mice provides further mechanistic insights into the complex RTT pathogenesis. The deregulated pathways that were identified-in particular the markedly affected amino acid and carbohydrate metabolism-confirm a complex and multifaceted metabolic component in RTT, which in turn signifies putative therapeutic targets. Furthermore, the deregulated key metabolites provide a choice of potential biomarkers for a more detailed rating of disease severity and disease progression.

The neurodevelopmental disorder Rett syndrome (RTT) affects mostly females. Upon an apparently normal initial development, cognitive impairment, irregular breathing, motor dysfunction, and epilepsy occur. The complex pathogenesis includes, among others, mitochondrial impairment, redox imbalance, and oxidative damage. As these arise already in neonatal Rett mice, they were proposed contributors of disease progression. Several mitochondrial studies in RTT used either full brains or selected brain regions only. Here, we mapped mitochondria-related ROS generation brain wide. Using sophisticated multi-sample spectrofluorimetry, H2O2 release by isolated mitochondria was quantified in a coupled reaction of Amplex UltraRed and horseradish peroxidase. All brain regions and the entire lifespan were characterized in male and female mice. In WT mice, mitochondrial H2O2 release was usually highest in cortex and lowest in hippocampus. Maximum rates occurred at postnatal day (PD) 10 and they slightly declined with further maturation. Already at PD 10, male and female Rett mice showed exaggerated mitochondrial H2O2 releases in first brain regions and persistent brain-wide increases from PD 50 on. Interestingly, female Rett mice were more intensely affected than male Rett mice, with their brainstem, midbrain and hippocampus being most severely struck. In conclusion, we used a reliable multi-sample cuvette-based assay on mitochondrial ROS release to perform brain-wide analyzes along the entire lifespan. Mitochondrial H2O2 release in Rett mice is intensified in all brain regions, affects hemizygous males and heterozygous females, and involves all maturational stages. Therefore, intensified mitochondrial H2O2 release seriously needs to be considered throughout RTT pathogenesis and may constitute a potential therapeutic target.

There is limited knowledge on the prevalence and risk factors of diabetic retinopathy (DR) in dialysis patients. We have investigated the association between diabetes mellitus and lipid-related biomarkers and retinopathy in hemodialysis patients. We reviewed 1,255 hemodialysis patients with type 2 diabetes mellitus (T2DM) who participated in the German Diabetes and Dialysis Study (4D Study). Associations between categorical clinical, biochemical variables and diabetic retinopathy were examined by logistic regression. On average, patients were 66 ± 8 years of age, 54% were male and the HbA1c was 6.7% ± 1.3%. DR, found in 71% of the patients, was significantly and positively associated with fasting glucose, HbA1c, time on dialysis, age, systolic blood pressure, body mass index and the prevalence of other microvascular diseases (e.g. neuropathy). Unexpectedly, DR was associated with high HDL cholesterol and high apolipoproteins AI and AII. Patients with coronary artery disease were less likely to have DR. DR was not associated with gender, smoking, diastolic blood pressure, VLDL cholesterol, triglycerides, and LDL cholesterol. In summary, the prevalence of DR in patients with type 2 diabetes mellitus requiring hemodialysis is higher than in patients suffering from T2DM, who do not receive hemodialysis. DR was positively related to systolic blood pressure (BP), glucometabolic control, and, paradoxically, HDL cholesterol. This data suggests that glucose and blood pressure control may delay the development of DR in patients with diabetes mellitus on dialysis.

Rett syndrome (RTT) is a neurodevelopmental disorder associated with disturbed neuronal responsiveness and impaired neuronal network function. Furthermore, mitochondrial alterations and a weakened cellular redox-homeostasis are considered part of the complex pathogenesis. So far, overshooting redox-responses of MeCP2-deficient neurons were observed during oxidant-mediated stress, hypoxia and mitochondrial inhibition. To further clarify the relevance of the fragile redox-balance for the neuronal (dys)function in RTT, we addressed more physiological stimuli and quantified the subcellular redox responses to neurotransmitter-stimulation. The roGFP redox sensor was expressed in either the cytosol or the mitochondrial matrix of cultured mouse hippocampal neurons, and the responses to transient stimulation by glutamate, serotonin, dopamine and norepinephrine were characterized. Each neurotransmitter evoked more intense oxidizing responses in the cytosol of MeCP2-deficient than in wildtype neurons. In the mitochondrial matrix the neurotransmitter-evoked oxidizing changes were more moderate and more uniform among genotypes. This identifies the cytosol as an important reactive oxygen species (ROS) source and as less stably redox buffered. Fura-2 imaging and extracellular Ca2+ withdrawal confirmed cytosolic Ca2+ transients as a contributing factor of neurotransmitter-induced redox responses and their potentiation in the cytosol of MeCP2-deficient neurons. Chemical uncoupling demonstrated the involvement of mitochondria. Nevertheless, cytosolic NADPH- and xanthine oxidases interact to play the leading role in the neurotransmitter-mediated oxidizing responses. As exaggerated redox-responses were already evident in neonatal MeCP2-deficient neurons, they may contribute remarkably to the altered neuronal network performance and the disturbed neuronal signaling, which are among the hallmarks of RTT.

BACKGROUND:Postoperative nausea and vomiting (PONV) is an extremely distressing side effect for patients. Despite PONV prophylaxis guided by well established scoring systems, the incidence of PONV is still high.OBJECTIVE:The aim of the current study was to investigate the predictive value of anxiety sensitivity as an additional independent risk factor for PONV in patients with an increased risk of PONV.DESIGN:A noninterventional, observational study.SETTING:A tertiary care university hospital.PATIENTS:Patients with an increased risk of PONV (i.e. female, nonsmoking) undergoing elective surgery (general, gynaecological, urological, musculoskeletal or neurosurgical) under general anaesthesia.MAIN OUTCOME MEASURES:The number of patients with anxiety sensitivity assessed pre-operatively with the Anxiety Sensitivity Index-3 questionnaire, the number of patients experiencing PONV, predictive value of anxiety sensitivity compared with other established risk factors for PONV.RESULTS:Some 41.5% of the patients experienced PONV within the first 24 h after surgery. In these patients increased anxiety sensitivity (Anxiety Sensitivity Index-3 score higher than seven points) was associated with a five-fold increase in the odds ratio (OR) for PONV. From the regression model, the risk of PONV was increased by lack of PONV prophylaxis (OR, 3.68), the postoperative administration of opioids (OR, 3.60) and patient age (OR, 1.03), but laparoscopic surgery did not increase the risk.CONCLUSION:In addition to the well established risk factors, anxiety sensitivity can help to predict the risk of PONV. It seems justifiable to add psychological factors such as anxiety sensitivity to PONV risk-scores. PONV prophylaxis should be considered when anxiety sensitivity is high.TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT01875120.