Indirect laryngoscopy is more effective than direct laryngoscopy when tracheal intubation is performed by novice operators: a systematic review, meta-analysis, and trial sequential analysis.

PURPOSE: We sought to perform a systematic review and meta-analysis to determine whether indirect laryngoscopy has an advantage over direct laryngoscopy in terms of the tracheal intubation rate, glottic visualization, and intubation time when used by novice operators. METHODS: We extracted adult prospective randomized trials comparing tracheal intubation with indirect vs direct laryngoscopy in novice operators from electronic databases. We extracted the following data from the identified studies: success rate, glottic visualization, and intubation time. Data from each trial were combined via a random-effects model to calculate the pooled relative risk (RR) or weighted mean difference (WMD) with a 95% confidence interval (CI). We also performed a trial sequential analysis. RESULTS: We included 15 articles (17 trials) comprising 2,290 patients in the systematic review. Compared with the direct laryngoscopy, indirect laryngoscopy improved success rate (RR, 1.15; 95% CI, 1.07 to 1.24; P = 0.0002; I2 = 88%), glottic visualization (RR, 1.76; 95% CI, 1.36 to 2.28; P < 0.001; I2 = 85%), and intubation time (WMD, -9.06 sec; 95% CI, -16.4 to -1.76; P = 0.01; I2 = 98%) in tracheal intubation. Trial sequential analysis showed that the total sample size was sufficient to analyze the success rate and intubation time. CONCLUSION: In this systematic review, we found that the tracheal intubation success rate, glottic visualization, and intubation time were improved when novice operators used indirect laryngoscopy rather than direct laryngoscopy. Trial sequential analysis results indicated that the sample size was sufficient for examining the success rate and intubation time. STUDY REGISTRATION: PROSPERO (CRD42022309045); first registered 4 September 2022.

RéSUMé: OBJECTIF: Nous avons cherché à réaliser une revue systématique et une méta-analyse pour déterminer si la laryngoscopie indirecte présente un avantage par rapport à la laryngoscopie directe en termes de taux de succès d'intubation trachéale, de visualisation glottique et de temps d'intubation lorsqu'elle est utilisée par des opératrices et opérateurs novices. MéTHODE: Nous avons extrait des études randomisées prospectives chez l'adulte comparant l'intubation trachéale avec une laryngoscopie indirecte vs directe réalisée par des opérateurs et opératrices novices à partir de bases de données électroniques. Nous avons extrait les données suivantes des études identifiées : taux de succès, visualisation glottique et temps d'intubation. Les données de chaque étude ont été combinées au moyen d'un modèle à effets aléatoires pour le calcul du risque relatif (RR) groupé ou de la différence moyenne pondérée (DMP) avec un intervalle de confiance (IC) de 95 %. Nous avons également réalisé une analyse séquentielle des études. RéSULTATS: Nous avons inclus 15 articles (17 études) portant sur 2290 patient·es dans notre revue systématique. Par rapport à la laryngoscopie directe, la laryngoscopie indirecte a amélioré le taux de succès (RR, 1,15; IC 95 %, 1,07 à 1,24; P = 0,0002; I2 = 88 %), la visualisation glottique (RR, 1,76; IC 95 %, 1,36 à 2,28; P < 0,001; I2 = 85 %), et le temps d'intubation (DMP, −9,06 s; IC 95 %, −16,4 à −1,76; P = 0,01; I2 = 98 %) pour l'intubation trachéale. L'analyse séquentielle des études a montré que la taille totale de l'échantillon était suffisante pour analyser le taux de succès et le temps d'intubation. CONCLUSION: Dans cette revue systématique, nous avons constaté que le taux de succès de l'intubation trachéale, la visualisation glottique et le temps d'intubation étaient améliorés lorsque les opératrices et opérateurs novices utilisaient la laryngoscopie indirecte plutôt que la laryngoscopie directe. L'analyse séquentielle des études a montré que la taille totale de l'échantillon était suffisante pour analyser le taux de succès et le temps d'intubation. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42022309045); première inscription le 4 septembre 2022.

Differences in prevalence of self-reported oral hypofunction between older adult patients with rheumatoid arthritis and the general older population: A cross-sectional study using propensity score matching.

OBJECTIVE: To examine the association between rheumatoid arthritis (RA) and oral hypofunction (OHF) using propensity score matching (PSM) to adjust for differences between older adults with RA and the general older adult population. METHODS: We conducted a cross-sectional survey among 189 older adults with RA in 2019 (mean age, 71.9 ± 3.6) and 47 178 independent older adult residents in 2016 (mean age, 71.6 ± 4.0), respectively. The questionnaire covered information on socio-demographic characteristics and OHF for both groups. Age, sex, educational level and smoking history were used to determine PSM. Prevalence ratios (PRs) and 95% confidence intervals (CIs) of self-reported OHF (fewer remaining teeth, decreased masticatory function, deterioration of swallowing function and oral dryness) were estimated using Poisson regressions. RESULT: OHF was observed in 44.4% of patients with RA and 27.5% of residents. Before PSM, the prevalence of OHF among patients with RA was higher than that of residents (PR, 1.75; 95% CI, 1.50-2.05). After PSM, there were 189 patients with RA and residents, and the prevalence of OHF among patients with RA was still higher (PR, 1.61; 95% CI, 1.22-2.13). Poisson regression showed that the prevalence of 19 or fewer teeth (PR, 1.06; 95% CI, 0.82-1.36), difficulties eating tough foods (PR, 1.18; 95% CI, 0.90-1.55), difficulties swallowing tea or soup (PR, 1.77; 95% CI, 1.19-2.63), and dry mouth (PR, 2.79; 95% CI, 1.90-4.07) was higher among patients with RA than residents. CONCLUSION: Compared with the general older adult population, patients with RA have a higher prevalence of self-reported OHF.

Lipopolysaccharide Priming Exacerbates Anaphylatoxin C5a-Induced Anaphylaxis in Mice.

Anaphylaxis is a serious allergic or hypersensitivity reaction with a sudden onset that can be life-threatening or fatal. Previous studies have highlighted two pathways of anaphylaxis in mice. One is the classical immunoglobulin E (IgE)-mediated pathway that involves mast cells and histamine. The other is an alternative IgG-mediated pathway that involves basophils, monocytes/macrophages, neutrophils, and the platelet-activating factor (PAF). However, little is known about the mechanism by which complement anaphylatoxins contribute to the induction of anaphylaxis. Infection is a cofactor that potentially amplifies the risk of anaphylaxis. Here, we showed that priming with a lipopolysaccharide (LPS), which mimics bacterial infection, exacerbates anaphylatoxin C5a-induced anaphylaxis in mice. LPS plus C5a-induced anaphylaxis was mediated by histamine and lipid mediators, especially PAF. Cell depletion experiments demonstrated that LPS plus C5a-induced anaphylaxis depended on monocytes/macrophages, basophils, and neutrophils. These results suggest that C5a is a potent inducer of anaphylaxis in bacterial infections. Remarkably, the molecular and cellular mediators of LPS plus C5a-induced anaphylaxis are mostly shared with IgE- and IgG-mediated anaphylaxis. Therefore, combined inhibition of histamine and PAF may be beneficial as a second-line treatment for severe anaphylaxis.

Airtraq® versus GlideScope® for tracheal intubation in adults: a systematic review and meta-analysis with trial sequential analysis.

PURPOSE: In recent years, various types of indirect laryngoscopes have been developed. Nevertheless, no conclusions have been drawn about which type of indirect laryngoscope is most effective for tracheal intubation. We performed a systematic review and meta-analysis to determine whether the Airtraq® or the GlideScope® is more effective for tracheal intubation. METHODS: We extracted studies of adult prospective randomized trials comparing tracheal intubation between the Airtraq and GlideScope. An electronic database was used to extract the studies included in our meta-analysis. We extracted the following data from the identified studies: success rate, glottic visualization, and intubation time. Data from each trial were combined via a random-effects model for calculation of pooled relative risk (RR) or weighted mean difference (WMD) with a 95% confidence interval (CI). We also performed trial sequential analysis. RESULTS: We included eight trials comprising 571 patients for review. Compared with the GlideScope, Airtraq did not improve success rate, glottic visualization, or intubation time in tracheal intubation (success rate: RR, 0.98; 95% CI, 0.91 to 1.05; P = 0.58; I2 = 65%; glottic visualization: RR, 1.07; 95% CI, 0.88 to 1.29; P = 0.69; I2 = 64%; and intubation time: WMD, 1.4 seconds ; 95% CI, -6.2 to 9.1; P = 0.72; I2 = 96%). The quality of evidence was graded as "very low." Trial sequential analysis showed that total sample size did not reach the required information size for all parameters. CONCLUSION: In this meta-analysis, use of the Airtraq indirect laryngoscope did not result in improved success rate, glottic visualization, or intubation time in tracheal intubation compared with the GlideScope. Trial sequential analysis suggests that further studies are necessary to confirm these findings.

RéSUMé: OBJECTIF: Ces dernières années, différents types de laryngoscopes indirects ont été mis au point. Néanmoins, aucune conclusion n'a été tirée sur le type de laryngoscope indirect le plus efficace pour l'intubation trachéale. Nous avons réalisé une revue systématique et une méta-analyse pour déterminer quel dispositif était le plus efficace pour l'intubation trachéale, soit l'Airtraq® ou le GlideScope®. MéTHODE: Nous avons extrait les études portant sur les essais randomisés prospectifs chez l'adulte comparant l'intubation trachéale avec l'Airtraq ou le GlideScope. Une base de données électronique a été utilisée pour extraire les études incluses dans notre méta-analyse. Nous avons extrait les données suivantes des études identifiées : taux de réussite, visualisation glottique et temps d'intubation. Les données de chaque étude ont été combinées au moyen d'un modèle à effets aléatoires pour le calcul du risque relatif (RR) groupé ou de la différence moyenne pondérée (DMP) avec un intervalle de confiance (IC) de 95 %. Nous avons également réalisé une analyse séquentielle des études. RéSULTATS: Nous avons inclus huit études portant sur 571 patients pour notre revue. Par rapport au GlideScope, l'Airtraq n'a pas amélioré le taux de réussite, la visualisation glottique ou le temps d'intubation pour l'intubation trachéale (taux de réussite : RR, 0,98; IC 95 %, 0,91 à 1,05; P = 0,58; I2 = 65 %; visualisation glottique : RR, 1.07; IC 95 %, 0,88 à 1,29; P = 0,69; I2 = 64 %; et temps d'intubation : DMP, 1,4 seconde; IC 95 %, -6,2 à 9,1; P = 0,72; I2 = 96 %). La qualité des données probantes a été classée comme « très faible ¼. L'analyse séquentielle des études a montré que la taille totale de l'échantillon n'atteignait pas la taille d'information requise pour tous les paramètres. CONCLUSION: Selon cette méta-analyse, l'utilisation du laryngoscope indirect Airtraq® n'entraîne pas d'amélioration du taux de réussite, de la visualisation glottique ou du temps d'intubation pour une intubation trachéale par rapport au GlideScope®. L'analyse séquentielle des études suggère que d'autres études sont nécessaires pour confirmer ces résultats.

Melatonin MT2 receptor is expressed and potentiates contraction in human airway smooth muscle.

Nocturnal asthma is characterized by heightened bronchial reactivity at night, and plasma melatonin concentrations are higher in patients with nocturnal asthma symptoms. Numerous physiological effects of melatonin are mediated via its specific G protein-coupled receptors (GPCRs) named the MT1 receptor, which couples to both Gq and Gi proteins, and the MT2 receptor, which couples to Gi. We investigated whether melatonin receptors are expressed on airway smooth muscle; whether they regulate intracellular cyclic AMP (cAMP) and calcium concentrations ([Ca2+]i), which modulate airway smooth muscle tone; and whether they promote airway smooth muscle cell proliferation. We detected the mRNA and protein expression of the melatonin MT2 but not the MT1 receptor in native human and guinea pig airway smooth muscle and cultured human airway smooth muscle (HASM) cells by RT-PCR, immunoblotting, and immunohistochemistry. Activation of melatonin MT2 receptors with either pharmacological concentrations of melatonin (10-100 µM) or the nonselective MT1/MT2 agonist ramelteon (10 µM) significantly inhibited forskolin-stimulated cAMP accumulation in HASM cells, which was reversed by the Gαi protein inhibitor pertussis toxin or knockdown of the MT2 receptor by its specific siRNA. Although melatonin by itself did not induce an initial [Ca2+]i increase and airway contraction, melatonin significantly potentiated acetylcholine-stimulated [Ca2+]i increases, stress fiber formation through the MT2 receptor in HASM cells, and attenuated the relaxant effect of isoproterenol in guinea pig trachea. These findings suggest that the melatonin MT2 receptor is expressed in ASM, and modulates airway smooth muscle tone via reduced cAMP production and increased [Ca2+]i.

Comparison of Hemodynamic Responses to Administration of Vasopressin and Norepinephrine Under General Anesthesia: A Systematic Review and Meta-analysis of Randomized Controlled Trials with Trial Sequential Analysis.

OBJECTIVE: The authors performed a meta-analysis to determine if vasopressin improves hypotension more than norepinephrine under general anesthesia. DESIGN: Meta-analysis. SETTING: Operating room. PATIENTS: Patients who underwent surgery, with general anesthesia. INTERVENTIONS: Administration of vasopressin or norepinephrine in order to increase blood pressure. MEASUREMENTS AND MAIN RESULTS: The primary outcome of this study was to determine if vasopressin increased mean blood pressure more effectively compared with norepinephrine for patients under general anesthesia. The secondary outcome was to see if vasopressin increased heart rate (HR), central venous pressure (CVP), cardiac output (CO), and cardiac index (CI) more significantly compared with norepinephrine under general anesthesia. The authors calculated the weighted mean difference, with 95% confidence interval (CI) using the random-effects model, and calculated the required information size (RIS) by performing trial sequential analysis (TSA). The authors selected 6 studies for analysis. Vasopressin did not improve hypotension compared with norepinephrine under general anesthesia. (weighted mean difference = -0.84 mmHg, 95% CI: -5.90 to 4.23, p = 0.75, Cochran Q = 24.6, I2 = 84%) In TSA, only 35.5% of RIS was achieved. Similarly, vasopressin and norepinephrine were not significantly different in terms of HR, CVP, CO, and CI. In TSA, only 23.7% of the RIS was reached for HR but RIS was almost achieved for CVP and CO. CONCLUSIONS: Vasopressin did not improve hypotension compared with norepinephrine under general anesthesia. The RIS was not reached in TSA, and Grading of Recommendations Assessment, Development and Evaluation is very low. Therefore, further research is needed to reach more robust conclusions.

Asystole Triggered by the Mouth Opening With a Dental Mouth Gag Under General Anesthesia During Pediatric Oral Surgery: Report of a Rare Case.

The trigeminovagal reflex manifests as a sudden onset of bradycardia, hypotension, and cardiac arrest in response to the stimulation of the trigeminal nerve. The incidence of trigeminovagal reflex in maxillofacial surgical procedures is approximately 1.6%. We report a case of asystole in a pediatric patient in whom a dental mouth gag triggered the trigeminovagal reflex during oral surgery. The patient was a 5-year-old boy who was scheduled to undergo extraction of maxillary supernumerary teeth. After tracheal intubation, anesthesia was maintained with sevoflurane and remifentanil. At the beginning of the surgery, his mouth was opened with a dental mouth gag, and electrocardigram showed asystole for 20 seconds. Thereafter, his heart rate spontaneously returned to basal value within 60 seconds. Since sufficient mouth opening was required to conduct the surgery, his mouth was opened again with the gag. When the interincisal distance exceeded about 40 mm, his heart rate suddenly decreased, but spontaneously returned to baseline within 60 second. The subsequent anesthetic course was uneventful.

The short-chain free fatty acid receptor FFAR3 is expressed and potentiates contraction in human airway smooth muscle.

Emerging evidence suggests that gut microbiota-derived short-chain fatty acids (SCFAs; acetate, propionate, and butyrate) are important modulators of the inflammatory state in diseases such as asthma. However, the functional expression of the Gi protein-coupled free fatty acid receptors (FFAR2/GPR43 and FFAR3/GPR41) has not been identified on airway smooth muscle (ASM). Classically, acute activation of Gi-coupled receptors inhibits cyclic AMP (cAMP) synthesis, which impairs ASM relaxation and can also induce crosstalk between Gi- and Gq-signaling pathways, potentiating increases in intracellular Ca2+ concentration ([Ca2+]i), favoring ASM contraction. In contrast, chronic activation of Gi-coupled receptors can sensitize adenylyl cyclase resulting in increased cAMP synthesis favoring relaxation. We questioned whether the Gi-coupled FFAR2 or FFAR3 is expressed in human ASM, whether they modulate cAMP and [Ca2+]i, and whether SCFAs modulate human ASM tone. We detected the protein expression of FFAR3 but not FFAR2 in native human ASM and primary cultured human airway smooth muscle (HASM) cells. In HASM cells, acute activation of FFAR3 with SCFAs inhibited forskolin-stimulated cAMP accumulation, but chronic activation did not sensitize cAMP synthesis. SCFAs induced [Ca2+]i increases that were attenuated by pertussis toxin, gallein, U73122, or xestospongin C. Acute treatment with SCFAs potentiated acetylcholine-stimulated [Ca2+]i increases and stress fiber formation in cells and contraction of ex vivo human airway tissues. In contrast, chronic pretreatment of human ASM with propionate did not potentiate airway relaxation. Together, these findings demonstrate that FFAR3 is expressed in human ASM and contributes to ASM contraction via reduced cAMP and increased [Ca2+]i.

Anesthetic management in MAO-A and MAO-B deficiency: a case report.

Monoamine oxidase (MAO) deficiency is an X-linked hereditary disease characterized by spontaneous deletion of MAO-A and/or MAO-B on the X chromosome. Here, we describe the first reported case of a patient with MAO-A and MAO-B deficiency managed under general anesthesia in dental treatment. The patient was aged 11 years old when he was scheduled for dental treatment. He was diagnosed with MAO-A and MAO-B deficiency on genetic testing at 2 years of age. He was not given premedication, and standard monitoring with noninvasive blood pressure monitoring, pulse oximetry, and ECG was instituted. We also preemptively prepared a cardioverter-defibrillator. General anesthesia was induced with propofol 46 mg (2 mg/kg), then rocuronium 10 mg (0.4 mg/kg) and remifentanil 0.30 µg/kg/min were administered via separate infusion pumps. Orotracheal intubation was performed without complications. Anesthesia was maintained uneventfully with a continuous infusion of remifentanil 0.15-0.2 µg/kg/min and propofol 5.0-7.0 mg/kg. Fresh gas flow included oxygen and air. End-tidal CO2 concentration was maintained at around 35 mmHg throughout the procedure. We administered sugammadex 92 mg (4 mg/kg) for reversal of neuromuscular blockade and the patient was extubated. We achieved successful anesthetic management without any appreciable clinical signs of fatal arrhythmias in this patient with MAO-A and MAO-B deficiency.

The free fatty acid receptor 1 promotes airway smooth muscle cell proliferation through MEK/ERK and PI3K/Akt signaling pathways.

Obesity is a risk factor for asthma and influences airway hyperresponsiveness, which is in part modulated by airway smooth muscle proliferative remodeling. Plasma free fatty acids (FFAs) levels are elevated in obese individuals, and long-chain FFAs act as endogenous ligands for the free fatty acid receptor 1 (FFAR1), which couples to both Gq and Gi proteins. We examined whether stimulation of FFAR1 induces airway smooth muscle cell proliferation through classical MEK/ERK and/or phosphoinositide 3-kinase (PI3K)/Akt signaling pathways. The long-chain FFAs (oleic acid and linoleic acid) and a FFAR1 agonist (GW9508) induced human airway smooth muscle (HASM) cell proliferation, which was inhibited by the MEK inhibitor U0126 and the PI3K inhibitor LY294002 . The long-chain FFAs and GW9508 increased phosphorylation of ERK, Akt, and p70S6K in HASM cells and freshly isolated rat airway smooth muscle. Downregulation of FFAR1 in HASM cells by siRNA significantly attenuated oleic acid-induced phosphorylation of ERK and Akt. Oleic acid-induced ERK phosphorylation was blocked by either the Gαi-protein inhibitor pertussis toxin or U0126 and was partially inhibited by either the Gαq-specific inhibitor YM-254890 or the Gßγ signaling inhibitor gallein. Oleic acid significantly inhibited forskolin-stimulated cAMP activity, which was attenuated by pertussis toxin. Akt phosphorylation was inhibited by pertussis toxin, the ras inhibitor manumycin A, the Src inhibitor PP1, or LY294002 . Phosphorylation of p70S6K by oleic acid or GW9508 was significantly inhibited by LY294002 , U0126, and the mammalian target of rapamycin (mTOR) inhibitor rapamycin. In conclusion, the FFAR1 promoted airway smooth muscle cell proliferation and p70S6K phosphorylation through MEK/ERK and PI3K/Akt signaling pathways.

The dopamine D1 receptor is expressed and induces CREB phosphorylation and MUC5AC expression in human airway epithelium.

Background: Dopamine receptors comprise two subgroups, Gs protein-coupled "D1-like" receptors (D1, D5) and Gicoupled "D2-like" receptors (D2, D3, D4). In airways, both dopamine D1 and D2 receptors are expressed on airway smooth muscle and regulate airway smooth muscle force. However, functional expression of the dopamine D1 receptor has never been identified on airway epithelium. Activation of Gs-coupled receptors stimulate adenylyl cyclase leading to cyclic AMP (cAMP) production, which is known to induce mucus overproduction through the cAMP response element binding protein (CREB) in airway epithelial cells. We questioned whether the dopamine D1 receptor is expressed on airway epithelium, and whether it promotes CREB phosphorylation and MUC5AC expression. Methods: We evaluated the protein expression of the dopamine D1 receptor on native human airway epithelium and three sources of cultured human airway epithelial cells including primary cultured airway epithelial cells, the bronchial epithelial cell line (16HBE14o-), and the pulmonary mucoepidermoid carcinoma cell line (NCI-H292) using immunohistochemistry and immunoblotting. To characterize the stimulation of cAMP through the dopamine D1 receptor, 16HBE14o- cells and NCI-H292 cells were treated with dopamine or the dopamine D1 receptor agonists (SKF38393 or A68930) before cAMP measurements. The phosphorylation of CREB by A68930 in both 16HBE14o- and NCI-H292 cells was measured by immunoblot. The effect of dopamine or A68930 on the expression of MUC5AC mRNA and protein in NCI-H292 cells was evaluated by real-time PCR and immunofluorescence staining, respectively. Results: The dopamine D1 receptor protein was detected in native human airway epithelium and three sources of cultured human airway epithelial cells. Dopamine or the dopamine D1-like receptor agonists stimulated cAMP production in 16HBE14o- cells and NCI-H292 cells, which was reversed by the selective dopamine D1-like receptor antagonists (SCH23390 or SCH39166). A68930 significantly increased phosphorylation of CREB in both 16HBE14o- and NCI-H292 cells, which was attenuated by the inhibitors of PKA (H89) and MEK (U0126). Expression of MUC5AC mRNA and protein were also increased by either dopamine or A68930 in NCI-H292 cells. Conclusions: These results suggest that the activation of the dopamine D1 receptor on human airway epithelium could induce mucus overproduction, which could worsen airway obstructive symptoms.

Early Postoperative Nociceptive Threshold and Production of Brain-Derived Neurotrophic Factor Induced by Plantar Incision Are Not Influenced with Minocycline in a Rat: Role of Spinal Microglia.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) from spinal microglia is crucial for aberrant nociceptive signaling in several pathological pain conditions, including postoperative pain. We assess the contribution of spinal microglial activation and associated BDNF overexpression to the early post-incisional nociceptive threshold. METHODS: Male Sprague-Dawley rats were implanted with an intrathecal catheter. A postoperative pain model was established by plantar incision. Thermal and mechanical nociceptive responses were assessed by infrared radiant heat and von Frey filaments before and after plantar incision. Rats were injected intrathecally the microglial activation inhibitor minocycline before incision, 24 h after incision, or both. Other groups were subjected to the same treatments and the L4-L5 spinal cord segment removed for immunohistochemical analysis of microglia activation and BNDF expression. RESULTS: Plantar incision reduced both thermal latency and mechanical threshold, indicating thermal hypersensitivity and mechanical allodynia. Minocycline temporally reduced thermal withdrawal latency but had no effect on mechanical withdrawal threshold, spinal microglial activity, or dorsal horn BDNF overexpression during the early post-incision period. CONCLUSION: These results suggest that spinal microglia does not contribute substantially to post-incisional nociceptive threshold. The BDNF overexpression response that may contribute to postoperative hyperalgesia and allodynia is likely derived from other sources.

Novel identification of the free fatty acid receptor FFAR1 that promotes contraction in airway smooth muscle.

Obesity is one of the major risk factors for asthma. Previous studies have demonstrated that free fatty acid levels are elevated in the plasma of obese individuals. Medium- and long-chain free fatty acids act as endogenous ligands for the free fatty acid receptors FFAR1/GPR40 and FFAR4/GPR120, which couple to Gq proteins. We investigated whether FFAR1 and FFAR4 are expressed on airway smooth muscle and whether they activate Gq-coupled signaling and modulate airway smooth muscle tone. We detected the protein expression of FFAR1 and FFAR4 in freshly dissected native human and guinea pig airway smooth muscle and cultured human airway smooth muscle (HASM) cells by immunoblotting and immunohistochemistry. The long-chain free fatty acids (oleic acid and linoleic acid) and GW9508 (FFAR1/FFAR4 dual agonist) dose-dependently stimulated transient intracellular Ca(2+) concentration ([Ca(2+)]i) increases and inositol phosphate synthesis in HASM cells. Downregulation of FFAR1 or FFAR4 in HASM cells by small interfering RNA led to a significant inhibition of the long-chain free fatty acids-induced transient [Ca(2+)]i increases. Oleic acid, linoleic acid, or GW9508 stimulated stress fiber formation in HASM cells, potentiated acetylcholine-contracted guinea pig tracheal rings, and attenuated the relaxant effect of isoproterenol after an acetylcholine-induced contraction. In contrast, TUG-891 (FFAR4 agonist) did not induce the stress fiber formation or potentiate acetylcholine-induced contraction. These results suggest that FFAR1 is the functionally dominant free fatty acid receptor in both human and guinea pig airway smooth muscle. The free fatty acid sensors expressed on airway smooth muscle could be an important modulator of airway smooth muscle tone.

Diurnal variation in asthma symptoms: Exploring the role of melatonin.

BACKGROUND: Asthma is a common chronic inflammatory disease affecting more than 260 million people worldwide. Nocturnal exacerbations of asthma symptoms significantly affect sleep quality and contribute to the most serious asthma exacerbations, which can lead to respiratory failure or death. Although ß2-adrenoceptor agonists are the standard of care for asthma, their bronchodilatory effect for nocturnal asthma is limited, and medications that specifically target symptoms of nocturnal asthma are lacking. HIGHLIGHT: Melatonin, which is secreted by the pineal gland, plays a crucial role in regulating circadian rhythms. Peak serum melatonin concentrations, which are inversely correlated with diurnal changes in pulmonary function, are higher in patients with nocturnal asthma than in healthy individuals. Melatonin potentiates bronchoconstriction through the melatonin MT2 receptor expressed in the smooth muscles of the airway and attenuates the bronchodilatory effects of ß2-adrenoceptor agonists, thereby exacerbating asthma symptoms. Melatonin inhibits mucus secretion and airway inflammation, potentially ameliorating asthma symptoms. CONCLUSION: Melatonin may exacerbate or ameliorate various pathophysiological conditions associated with asthma. As a potential therapeutic agent for asthma, the balance between its detrimental effects on airway smooth muscles and its beneficial effects on mucus production and inflammation remains unclear. Further studies are needed to elucidate whether melatonin worsens or improves asthma symptoms.

Machine learning-based identification of the risk factors for postoperative nausea and vomiting in adults.

Postoperative nausea and vomiting (PONV) is a common adverse effect of anesthesia. Identifying risk factors for PONV is crucial because it is associated with a longer stay in the post-anesthesia care unit, readmissions, and perioperative costs. This retrospective study used artificial intelligence to analyze data of 37,548 adult patients (aged ≥20 years) who underwent surgery under general anesthesia at Tohoku University Hospital from January 1, 2010 to December 31, 2019. To evaluate PONV, patients who experienced nausea and/or vomiting or used antiemetics within 24 hours after surgery were extracted from postoperative medical and nursing records. We create a model that predicts probability of PONV using the gradient tree boosting model, which is a widely used machine learning algorithm in many applications due to its efficiency and accuracy. The model implementation used the LightGBM framework. Data were available for 33,676 patients. Total blood loss was identified as the strongest contributor to PONV, followed by sex, total infusion volume, and patient's age. Other identified risk factors were duration of surgery (60-400 min), no blood transfusion, use of desflurane for maintenance of anesthesia, laparoscopic surgery, lateral positioning during surgery, propofol not used for maintenance of anesthesia, and epidural anesthesia at the lumbar level. The duration of anesthesia and the use of either sevoflurane or fentanyl were not identified as risk factors for PONV. We used artificial intelligence to evaluate the extent to which risk factors for PONV contribute to the development of PONV. Intraoperative total blood loss was identified as the potential risk factor most strongly associated with PONV, although it may correlate with duration of surgery, and insufficient circulating blood volume. The use of sevoflurane and fentanyl and the anesthesia time were not identified as risk factors for PONV in this study.

The dopamine D1 receptor is expressed and facilitates relaxation in airway smooth muscle.

BACKGROUND: Dopamine signaling is mediated by Gs protein-coupled "D1-like" receptors (D1 and D5) and Gi-coupled "D2-like" receptors (D2-4). In asthmatic patients, inhaled dopamine induces bronchodilation. Although the Gi-coupled dopamine D2 receptor is expressed and sensitizes adenylyl cyclase activity in airway smooth muscle (ASM) cells, the Gs-coupled dopamine D1-like receptor subtypes have never been identified on these cells. Activation of Gs-coupled receptors stimulates cyclic AMP (cAMP) production through the stimulation of adenylyl cyclase, which promotes ASM relaxation. We questioned whether the dopamine D1-like receptor is expressed on ASM, and modulates its function through Gs-coupling. METHODS: The mRNA and protein expression of dopamine D1-like receptor subtypes in both native human and guinea pig ASM tissue and cultured human ASM (HASM) cells was measured. To characterize the stimulation of cAMP through the dopamine D1 receptor, HASM cells were treated with dopamine or the dopamine D1-like receptor agonists (A68930 or SKF38393) before cAMP measurements. To evaluate whether the activation of dopamine D1 receptor induces ASM relaxation, guinea pig tracheal rings suspended under isometric tension in organ baths were treated with cumulatively increasing concentrations of dopamine or A68930, following an acetylcholine-induced contraction with or without the cAMP-dependent protein kinase (PKA) inhibitor Rp-cAMPS, the large-conductance calcium-activated potassium (BKCa) channel blocker iberiotoxin, or the exchange proteins directly activated by cAMP (Epac) antagonist NSC45576. RESULTS: Messenger RNA encoding the dopamine D1 and D5 receptors were detected in native human ASM tissue and cultured HASM cells. Immunoblots confirmed the protein expression of the dopamine D1 receptor in both native human and guinea pig ASM tissue and cultured HASM cells. The dopamine D1 receptor was also immunohistochemically localized to both human and guinea pig ASM. The dopamine D1-like receptor agonists stimulated cAMP production in HASM cells, which was reversed by the selective dopamine D1-like receptor antagonists SCH23390 or SCH39166. A68930 relaxed acetylcholine-contracted guinea pig tracheal rings, which was attenuated by Rp-cAMPS but not by iberiotoxin or NSC45576. CONCLUSIONS: These results demonstrate that the dopamine D1 receptors are expressed on ASM and regulate smooth muscle force via cAMP activation of PKA, and offer a novel target for therapeutic relaxation of ASM.

Anesthetic Management of a Patient With Spinocerebellar Ataxia Type 1.

Spinocerebellar ataxia type 1 (SCA1) is one of the autosomal dominant spinocerebellar degeneration (SCD) diseases characterized by progressive cerebellar ataxia, muscle atrophy, and peripheral neuropathy. We report the management of a 43-year-old man with SCA1 who underwent general anesthesia for open reduction and internal fixation of a mandibular fracture. Although anesthesia-induced vocal cord paralysis has been reported in patients with SCD, nasotracheal intubation was performed uneventfully with video laryngoscope. After taking into consideration the increased risk of postoperative respiratory depression in patients with SCD, rocuronium dosing was titrated carefully, and fentanyl was not used during surgery. Preparation for an anticipated difficult airway and avoiding significant respiratory depression are crucial when providing general anesthesia for patients with SCA1.

Successful Tracheal Intubation With Airway Scope After Failure With McGrath.

The use of video laryngoscopy is growing in patients with anatomical factors suggestive of a difficult airway. This case report describes the successful tracheal intubation of a 54-year-old female patient with limited mouth opening scheduled for third molar extraction under general anesthesia. The Airway scope (AWS) along with a gum-elastic bougie was used to secure the airway after failed direct laryngoscopy and video laryngoscopy using the McGrath MAC with an X-blade. The AWS has a J-shaped structure in which the blade approximates the curvature of the pharynx and larynx. This blade shape makes it easy to match the laryngeal axis with the visual field direction, enabling successful tracheal intubation even for patients with limited mouth opening. A major key to successful video laryngoscopy is to select a video laryngoscope based on the anatomical characteristics of patients with a difficult airway.

Comparison of Indirect and Direct Laryngoscopes in Pediatric Patients with a Difficult Airway: A Systematic Review and Meta-Analysis.

This meta-analysis was performed to determine whether an indirect laryngoscope is more advantageous than a direct laryngoscope for tracheal intubation in the setting of a difficult pediatric airway. Data on the intubation failure and intubation time during tracheal intubation were extracted from prospective and retrospective studies identified through a comprehensive literature search. Data from 10 individual articles (11 trials) were combined, and a DerSimonian and Laird random-effects model was used to calculate either the pooled relative risk (RR) or the weighted mean difference (WMD) and the corresponding 95% confidence interval (CI). Meta-analysis of the 10 articles indicated that the intubation failure of tracheal intubation with an indirect laryngoscope was not significantly different from that of a direct laryngoscope in patients with a difficult airway (RR 0.86, 95% CI 0.51-1.46; p = 0.59; Cochrane's Q = 50.5; I2 = 82%). Intubation time with an indirect laryngoscope was also similar to that with a direct laryngoscope (WMD 4.06 s; 95% CI -1.18-9.30; p = 0.13; Cochrane's Q 39.8; I2 = 85%). In conclusion, indirect laryngoscopes had the same intubation failure and intubation time as direct laryngoscopes in pediatric patients with a difficult airway. Currently, the benefits of indirect laryngoscopes have not been observed in the setting of a difficult pediatric airway.