Poor preoperative performance at Clock Drawing Test is associated with postoperative decline in olfaction in older patients: an observational pilot study.

BACKGROUND: Decline in olfaction may occur after general anesthesia, but the exact incidence and underlying physiopathology remain scarcely investigated. Olfactory dysfunction arises with aging and is known to be linked to cognitive impairment. In this pilot study, we evaluated the incidence of immediate postoperative decline in olfaction and its association with a preoperative cognitive test, performance at Clock Drawing Test (CDT), in a group of older patients. METHODS: This pilot study is a sub-analysis of a prospective observational study. Patients ≥ 65 years old and scheduled for elective non-cardiac surgery under sevoflurane-based anesthesia were enrolled. CDT was part of the preoperative evaluation. We assessed olfaction on the day before and the day after surgery (between 16 and 26 h postoperatively) using the Sniffin' Sticks 12-item identification test, which consists of pen-like devices displaying 12 different odors. Postoperative decline in olfaction was defined as a decrease of at least 1 standard deviation in the olfactory score. RESULTS: We included a total of 93 patients, among whom 19 (20.4%) presented a postoperative decline in olfaction. The incidence of postoperative decline in olfaction was higher in the "CDT low-score" (score ≤ 5/8) group (11/34, 32.4%) than in the "CDT high-score" (score ≥ 6/8) group (8/58, 13.6%) (P = 0.030). Despite adjusting for confounding variables, CDT score remained independently associated with immediate postoperative decline in olfactory identification function (OR 0.67, 95% CI 0.48 to 0.94, P = 0.022). CONCLUSIONS: Postoperative decline in olfaction occurred in 20.4% of older patients and was associated with poor preoperative performance at CDT. TRIAL REGISTRATION: This study was retrospectively registered on https://clinicaltrials.gov/ under the NCT04700891 number (principal investigator: Victoria Van Regemorter), in December 2020.

Combined Use of Rotational Thromboelastometry (Rotem) and Platelet Impedance Aggregometry (Multiplate Analyzer) in Cyanotic and Acyanotic Infants and Children Undergoing Cardiac Surgery With Cardiopulmonary Bypass: Subgroup Analysis of a Randomized Clinical Trial.

OBJECTIVES: Few studies have investigated the Multiplate platelet function analyzer in pediatrics. The authors evaluated Multiplate combined with Rotem in terms of guiding platelet transfusion after pediatric cardiac surgery with cardiopulmonary bypass (CPB). The authors further compared coagulation parameters between cyanotic and acyanotic patients. DESIGN: Subgroup analysis of a randomized clinical trial. SETTING: Tertiary hospital. PARTICIPANTS: Patients weighing between seven and 15 kg. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Rotem and Multiplate tests were performed (1) after anesthesia induction, (2) upon CPB separation, and (3) upon intensive care unit arrival. Among a total of 59 subjects, 9 patients required platelet transfusion. In multivariate linear regression, analysis EXTEM maximum clot firmness upon CPB separation was associated with the volume of transfused platelets (regression coefficient = -0.348 [95% confidence interval -1.006 to -0.028]; p = 0.039). No such association was found for the Multiplate test. Acyanotic and cyanotic heart disease were present in 32 and 27 children, respectively. There were no significant differences between these two groups in terms of platelet count and function. Postoperative blood loss was significantly higher in the cyanotic group compared with the acyanotic arm (p = 0.015; difference [95% confidence interval -2.40 {-4.20 to -0.60}]). There were no differences between groups regarding transfusion of allogeneic blood products. CONCLUSIONS: This study showed that Rotem, but not Multiplate results, were associated with platelet transfusion in pediatric cardiac surgery with no intake of platelet inhibitors. The usefulness of combining these tests in platelet transfusion decision-making needs to be evaluated in larger populations.

Downregulation of Caveolin-1 and Upregulation of Deiodinase 3, Associated with Hypoxia-Inducible Factor-1α Increase, Are Involved in the Oxidative Stress of Graves' Orbital Adipocytes.

Background: Even though the clinical features of Graves' orbitopathy (GO) are well known, its exact pathogenesis remains controversial. The imbalance of redox homeostasis in the connective tissue could play a crucial role leading to an inflammatory state and edema of soft orbital tissues, thus contributing to orbital hypoxia and increase in hypoxia-inducible factor (HIF)-1α. This oxidative stress appears to target the orbital cells such as fibroblasts and also adipocytes. This study aims to explore which pathways can lead to the aforementioned oxidative stress in GO adipose cells and therefore offers new plausible therapeutic targets. Methods: Orbital fat samples were obtained from patients with GO (Western blot [WB]: n = 8, immunohistochemistry [IHC]: n = 8) and from control patients (WB: n = 5, IHC: n = 3-5). They were processed for WB analysis and IHC of the antioxidants (catalase, superoxide dismutase 1) and for HIF-1α. The expression of caveolin-1 (Cav-1) and deiodinase 3 (DIO3), known to be regulated by HIF-1α, was also analyzed by WB and IHC, as well as the targets of Cav-1: glucose transporter type 4 (Glut-4), NADPH oxidase (NOX)-2, and endothelial nitric oxide synthase (eNOS). Triiodothyronine (T3) expression was also analyzed by IHC. Results: In GO adipocytes, the expression of catalase was reduced, whereas that of HIF-1α was strongly increased. A decreased local T3 supply was associated with DIO3 upregulation. The low expression of Cav-1 in GO adipocytes was associated not only with low expression of Glut-4 but also with an increased expression of NOX-2 and active eNOS phosphorylated on serine 1177. Conclusions: Cav-1 and DIO3, both sensitive to hypoxia and to the increase of HIF-1α, play a pivotal role in the oxidative stress in GO adipocytes. DIO3 regulates the cellular supply of T3, which is essential for the cell homeostasis. Cav-1 determines the cellular glucose supply through Glut-4 and regulates the activity of NOX-2 generating superoxide anions and that of eNOS generating nitric oxide (NO).

Mechanisms Linking Olfactory Impairment and Risk of Mortality.

Olfaction is a sense involved in a complex set of tasks, influencing eating behavior, increasing awareness of environmental hazards and affecting social communication. Surprisingly, smell disorders are very frequent, especially in the elderly population. Several recent studies conducted mostly in older subjects have demonstrated a strong association between olfactory impairment and overall mortality risk, with anosmia being even more predictive of 5 years mortality risk than cardiovascular disease. Presently, the underlying pathophysiology linking olfactory impairment to mortality remains unknown and only putative mechanisms are suggested. This review aims to examine the link between olfactory impairment and mortality and to discuss existing ideas on underlying existing mechanisms including, (1) the effect of olfactory loss on nutrition, life-threatening situations and social interactions, (2) associated neurodegenerative diseases, (3) accelerated brain aging, and (4) reflection of general health status being reflected in olfactory function.

Electroencephalogram Suppression Despite Extremely Low-Dose Anesthetic During Cardiac Surgery: A Case Report.

A prominent feature of electroencephalogram (EEG) under general anesthesia is anteriorization of α waves. We report the case of a 63-year-old man anesthetized for coronary artery bypass grafting in whom the NeuroSENSE-processed EEG monitor recorded only δ waves in the absence of α frequencies, along with high EEG suppression despite extremely low doses of anesthetics during the whole procedure. The patient fully recovered from anesthesia 2 hours after the procedure and showed neither awareness nor neurological complications. This atypical EEG pattern under low concentration of anesthetics may be an intraoperative marker of a specific brain phenotype.

Successful ventilation through a Rüsch intubation guide catheter in severe laryngotracheal stenosis.

BACKGROUND: Providing adequate ventilation may remain complex in patients with severe proximal laryngotracheal stenosis, especially when the airway is shared with the surgeon during tracheal resection surgery. We describe an effective alternative to standard endotracheal intubation using a Rüsch flexible intubation guide catheter. METHODS: In two patients undergoing tracheal repair surgery, we failed to insert a 5.0 inner diameter endotracheal tube (6.9 mm outer diameter) or a 6.0 mm outer diameter endoscope through the laryngotracheal stenosis. However, using indirect laryngoscopy, a 6.0 outer diameter Rüsch flexible intubation guide catheter was passed successfully through the vocal cords and then through the stenosis. Controlled ventilation was achieved by means of the Rüsch guide, provided with its two large Murphy's eyes. When the trachea was opened, the Rüsch guide was removed just enough for the surgeons to place a Montandon tracheal tube, at that point taking over ventilation. A 7.0 inner diameter endotracheal cuffed tube had been inserted onto the Rüsch guide and left pending upstream from the vocal cords. Once the posterior tracheal wall was sutured, this endotracheal cuffed tube was slid along the Rüsch guide through the vocal cords with the cuff placed beyond the tracheal sutures. RESULTS: Controlled ventilation through the Rüsch flexible intubation guide catheter showed satisfying and stable ventilatory parameters in both patients. Inspiratory pressures of 25-30 mmHg were enough to reach adequate tidal volumes around 450 ml. End tidal CO2 was kept between 35 and 40 mmHg (PaCO2 showed similar values). Standard endotracheal intubation at the end of the tracheal resection was easy and safe thanks to the Rüsch guide still in place between the vocal cords. CONCLUSIONS: We suggest an effective and reliable method using a Rüsch flexible intubation guide catheter for airway management in patients suffering from laryngotracheal stenosis in the setting of tracheal repair surgery.

Pioglitazone, a PPARγ Agonist, Upregulates the Expression of Caveolin-1 and Catalase, Essential for Thyroid Cell Homeostasis: A Clue to the Pathogenesis of Hashimoto's Thyroiditis.

BACKGROUND: Peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that regulates the expression of multiple target genes involved in several metabolic pathways as well as in inflammation. The expression and cell localization of caveolin-1 (Cav-1), thyroperoxidase (TPO), and dual oxidase (DUOX), involved in extracellular iodination, is modulated by Th1 cytokines in human normal thyroid cells and in Hashimoto's thyroiditis (HT). OBJECTIVES: The objectives of this study were (i) to analyze the PPARγ protein and mRNA expression at the follicular level in HT versus controls in correlation with the one of Cav-1; (ii) to study the effects of Th1 cytokines on PPARγ and catalase expression in human thyrocyte primary cultures; and (iii) to study the effects of pioglitazone, a PPARγ agonist, on thyroxisome components (Cav-1, TPO, DUOX) and on catalase, involved in antioxidant defense. RESULTS: Although the global expression of PPARγ in the whole gland of patients with HT was not modified compared with controls, there was great heterogeneity among glands and among follicles within the same thyroid. Besides normal (type 1) follicles, there were around inflammatory zones, hyperactive (type 2) follicles with high PPARγ and Cav-1 expression, and inactive (type 3) follicles which were unable to form thyroxine and did not express PPARγ or Cav-1. In human thyrocytes in primary culture, Th1 cytokines decreased PPARγ and catalase expression; pioglitazone increased Cav-1, TPO, and catalase expression. CONCLUSION: PPARγ may play a central role in normal thyroid physiology by upregulating Cav-1, essential for the organization of the thyroxisome and extracellular iodination. By upregulating catalase, PPARγ may also contribute to cell homeostasis. The inhibitory effect of Th1 cytokines on PPARγ expression may be considered as a new pathogenetic mechanism for HT, and the use of PPARγ agonists could open a new therapeutic approach.

Oxidative Stress and Upregulation of Antioxidant Proteins, Including Adiponectin, in Extraocular Muscular Cells, Orbital Adipocytes, and Thyrocytes in Graves' Disease Associated with Orbitopathy.

BACKGROUND: Graves' orbitopathy (GO) is the main extrathyroidal manifestation associated with Graves' disease (GD). It is characterized by reduced eye motility due to an increased volume of orbital fat and/or of extraocular muscles (EOMs) infiltrated by fibrosis and adipose tissue. The pathogenetic mechanisms leading to fibrosis and adipogenesis are mainly based on the interaction between orbital fibroblasts and immune cells (lymphocytes and mast cells) infiltrating the GO EOMs. METHODS: Analysis of the morphological status, oxidative stress (OS), and antioxidant defenses in the orbital muscular cells and adipocytes in GO patients compared with controls was conducted. RESULTS: Both cell types are affected by OS, as shown by the increased expression of 4-hydroxynonenal, which leads to apoptosis in muscular cells. However, the EOMs and the adipocytes possess antioxidant defenses (peroxiredoxin 5 and catalase) against the OS, which are also upregulated in thyrocytes in GD. The expression of adiponectin (ApN) and proliferator-activated receptor gamma (PPARγ) is also increased in GO muscular cells and adipocytes. OS and antioxidant proteins expression are correlated to the level of blood antithyrotropin receptor antibodies (TSHR-Ab). CONCLUSION: Even when TSHR-Ab level is normalized, OS and antioxidant protein expression is high in EOM muscular cells and adipocytes in GO compared with controls. This justifies a supplementation with antioxidants in active as well as chronic GO patients. Orbital muscular cells are also the sources of PPARγ and ApN, which have direct or indirect local protective effects against OS. Modulation of these proteins could be considered as a future therapeutic approach for GO.

The expression of dual oxidase, thyroid peroxidase, and caveolin-1 differs according to the type of immune response (TH1/TH2) involved in thyroid autoimmune disorders.

CONTEXT: Hashimoto's thyroiditis (HT) and Graves' disease (GD) are thyroid autoimmune disorders driven by Th1 and Th2 immune responses, respectively. Caveolin-1 (Cav-1), thyroid peroxidase (TPO), and dual oxidase (DUOX) are thought to be part of the thyroxisome, which is essential to maintain thyroid hormone synthesis, at the apical membrane. OBJECTIVES: To analyze the thyroxisome in HT and GD thyroids, we investigated Cav-1, DUOX, and TPO expression as well as markers of oxidative stress (OS), cell proliferation, apoptosis, and antioxidant defenses. The effects of cytokines on Cav-1 expression were analyzed in vitro. RESULTS: In HT, the decrease in Cav-1, DUOX, and TPO expression was marked in follicles having the morphological aspect of active follicles in normal glands and thus called active-like follicles. T4 was not detected in the colloid but in the cytoplasm as well as DUOX and TPO. These abnormalities were associated with increased OS and cell damage. In the hypofunctioning follicles of HT and normal thyroids, Cav-1, DUOX, and TPO were not expressed. In GD, they were expressed at the apical pole of thyrocytes, and T4 accumulated in the colloid of all follicles. Th1 cytokines IL-1α/interferonγ decreased Cav-1 expression in vitro, whereas the Th2 cytokine IL-4 had no effect. CONCLUSION: Th1 cytokine-induced down-regulation of Cav-1 could be responsible for intracytoplasmic T4 synthesis and mislocalization of DUOX and TPO, suggesting an important role for Cav-1 in the preservation of thyroxisome integrity. The thyroxisome's disruption, leading to uncontrolled OS and cell apoptosis, is a key, event in HT pathogenesis.