Supraglottic Jet Oxygenation and Ventilation to Minimize Hypoxia in Patients Receiving Flexible Bronchoscopy Under Deep Sedation: A 3-Arm Randomized Controlled Trial.

BACKGROUND: Hypoxia often occurs due to shared airway and anesthetic sedation-induced hypoventilation in patients receiving flexible bronchoscopy (FB) under deep sedation. Previous evidence has shown that supraglottic jet oxygenation and ventilation (SJOV) via Wei nasal jet tube (WNJ) reduces the incidence of hypoxia during FB. This study aimed to investigate the extent to which SJOV via WNJ could decrease the incidence of hypoxia in patients under deep sedation as compared to oxygen supplementation via WNJ alone or nasal catheter (NC) for oxygen supplementation during FB. METHODS: This was a single-center 3-arm randomized controlled trial (RCT). Adult patients scheduled to undergo FB were randomly assigned to 3 groups: NC (oxygen supplementation via NC), low-pressure low-flow (LPLF) (low-pressure oxygen supplementation via WNJ alone), or SJOV (high-pressure oxygen supplementation via WNJ). The primary outcome was hypoxia (defined as peripheral saturation of oxygen [Sp o2 ] <90% lasting more than 5 seconds) during FB. Secondary outcomes included subclinical respiratory depression or severe hypoxia, and rescue interventions specifically performed for hypoxia treatment. Other evaluated outcomes were sore throat, xerostomia, nasal bleeding, and SJOV-related barotraumatic events. RESULTS: One hundred and thirty-two randomized patients were included in 3 interventions (n = 44 in each), and all were included in the final analysis under intention to treat. Hypoxia occurred in 4 of 44 patients (9.1%) allocated to SJOV, compared to 38 of 44 patients (86%) allocated to NC, with a relative risk (RR) for hypoxia, 0.11; 98% confidence interval (CI), 0.02-0.51; P < .001; or to 27 of 44 patients (61%) allocated to LPLF, with RR for hypoxia, 0.15; 95% CI, 0.04-0.61; P < .001, respectively. The percentage of subclinical respiratory depression was also significantly diminished in patients with SJOV (39%) compared with patients with NC (100%) or patients with LPLF (96%), both P < .001. In SJOV, no severe hypoxia event occurred. More remedial interventions for hypoxia were needed in the patients with NC. Higher risk of xerostomia was observed in patients with SJOV. No severe adverse event was observed throughout the study. CONCLUSIONS: SJOV via WNJ effectively reduces the incidence of hypoxia during FB under deep sedation.

Supraglottic jet oxygenation and ventilation improves oxygenation during endoscopic retrograde cholangiopancreatography: a randomized controlled clinical trial.

PURPOSE: Hypoxia is one of the most frequent adverse events under deep sedation in the semiprone position. We hypothesized that supraglottic jet oxygenation and ventilation (SJOV) via Wei nasal jet tube (WNJ) can reduce the incidence of hypoxia in patients under deep sedation during endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A total of 171 patients were divided into three groups: N group, supplementary oxygen via a nasopharyngeal airway (4-6 L/min); W group, supplementary oxygen via WNJ (4-6 L/min); WS group, SJOV via WNJ. The primary outcome was the incidence of adverse events, including sedation-related adverse events [SRAEs, hypoxemia (SpO2 = 75-89% lasted less than 60 s); severe hypoxemia (SpO2 < 75% at any time or SpO2 < 90% lasted more than 60 s] and subclinical respiratory depression (SpO2 = 90-95%). Other intraoperative and post-operative adverse events were also recorded as secondary outcomes. RESULTS: Compared with the N group, the incidence of hypoxemia and subclinical respiratory depression in the WS group was significantly lower (21% vs. 4%, P = 0.005; 27% vs. 6%, P = 0.002). Compared with Group W, the incidence of hypoxemia and subclinical respiratory depression in Group WS was also significantly less frequent (20% vs. 4%, P = 0.009; 21% vs. 6%, P = 0.014). No severe hypoxia occurred in the group WS, while four and one instances were observed in the group N and group W respectively. There were no significant differences in other adverse events among the three groups. CONCLUSION: SJOV can effectively improve oxygenation during ERCP in deeply sedated semiprone patients.

Airway collapse hinders recovery in bronchoscopy therapy for postintubation tracheal stenosis patients.

BACKGROUND: Expiratory central airway collapse (ECAC) following postintubation airway stenosis (PITS) is a rare phenomenon. The impact of airway malacia and collapse on the prognosis and the success rate of bronchoscopic interventional therapy in patients with PITS had been inadequately investigated. OBJECTIVE: The aim of this research was to assess the influence of airway malacia and collapse on the efficacy of bronchoscopic interventional therapy in patients with PITS. DESIGN: This retrospective analysis examined the medical documentation of individuals diagnosed with PITS who underwent bronchoscopic intervention at the tertiary interventional pulmonology center of Emergency General Hospital from 2014 to 2021. MAIN OUTCOME MEASURES: Data pertaining to preoperative, perioperative, and postoperative stages were documented and subjected to analysis. RESULTS: The patients in malacia and collapse group (MC group) exhibited a higher frequency of perioperative complications, including intraoperative hypoxemia, need for reoperation within 24 h, and postoperative intensive care unit admission rate (P < 0.05, respectively). Meanwhile, patients in group MC demonstrated significantly worse postoperative scores (higher mMRC score and lower KPS score) compared to those in pure stenosis group (P < 0.05, respectively), along with higher degrees of stenosis after treatment and a lower success rate of bronchoscopic intervention therapy cured (P < 0.05, respectively). Pearson analysis results showed that these terms were all significantly correlated with the occurrence of airway malacia and collapse in the airway (P < 0.05, respectively). CONCLUSION: The presence of malacia or collapse in patients with PITS was associated with increased perioperative complications following bronchoscopic interventional therapy, and significantly reduced the long-term cure rate compared to patients with pure tracheal stenosis. Trial registration Chinese Clinical Trial Registry on 06/12/2021. REGISTRATION NUMBER: ChiCTR2100053991.

Evaluation of Supraglottic Jet Oxygenation and Ventilation in 105 Patients During Bronchoscopy Using the Twinstream® Microprocessor-Controlled Jet Ventilator and the Wei Nasal Jet® Tube.

BACKGROUND The Twinstream® ventilator is a microprocessor-controlled electric jet ventilator that allows the simultaneous application of 2 different jet streams, one at low frequency and one at high frequency to result in pulsatile bi-level (p-BLV) mode of ventilation. This study aimed to evaluate supraglottic jet oxygenation and ventilation in 105 patients during bronchoscopy using the Twinstream® microprocessor-controlled jet ventilator and the Wei Nasal Jet® (WNJ) tube. MATERIAL AND METHODS Patients were randomly divided into 2 parallel groups (N=50 per group): group W using the WNJ tube and group M using an endoscopic face mask connected to Twinstream® microprocessor-controlled jet ventilator under monitored anesthesia care. Arterial blood gas was examined and recorded 15 minutes after the initiation of procedure. The demographic and clinical characteristics, procedure duration, doses of anesthetics, and adverse events in the 2 groups were also recorded. RESULTS The arterial partial pressure of carbon dioxide (PaCO2) (P=0.006) and lactic acid (P=0.001) were significantly lower, while pH (P=0.024) was significantly higher than in the group M. Pearson analysis showed that PaCO2 was significantly correlated with ventilation tools (P=0.006) and procedure duration (P=0.003). Multiple linear regression analysis showed that ventilation tools and procedure duration were both independent influencing factors (P=0.006, P=0.002). CONCLUSIONS Supraglottic jet oxygenation and ventilation using the WNJ tube can reduce PaCO2 and had advantages in enhancing oxygenation and ventilation function in patients during bronchoscopy intervention therapy under monitored anesthesia care.

Lung isolation-a personalized and clinically adapted approach to control bronchoscopy-associated acute massive airway hemorrhage.

BACKGROUND: The current concept of bronchoscopy-associated massive airway hemorrhage is not accurate enough, and the amount of bleeding as the only evaluation criterion cannot comprehensively evaluate magnitude of the effects and the severity. OBJECTIVE: To propose the concept of bronchoscopy-associated acute massive airway hemorrhage, analyze its impact on patients and highlight the treatment approach of acute massive airway hemorrhage without ECMO support. DESIGNS: A retrospective cohort study. SETTING: Include all patients who received bronchoscopy intervention therapy at Interventional Pulmonology Center of Emergency General Hospital from 2004 to December 2021. PATIENTS: 223 patients met the inclusion criteria. INTERVENTION: Patients were divided into two groups: acute massive airway hemorrhage group (n = 29) and non-acute massive airway hemorrhage group (n = 194). MAIN OUTCOME MEASURES: Perioperative adverse events between two groups were the main outcome. Secondary outcome was the impact of lung isolation on patient in group Acute. RESULTS: The incidence of acute massive airway hemorrhage was 0.11%, and the incidence of non-acute massive airway hemorrhage was 0.76% in this study. There were significant differences in the incidence of intraoperative hypoxemia, lowest SpO2, hemorrhagic shock, cardiopulmonary resuscitation, intraoperative mortality, and transfer to ICU between acute group and non-acute group (P<0.05, respectively). Lung isolation was used in 12 patients with acute massive airway hemorrhage, and only 2 patients died during the operation. CONCLUSION: Bronchoscopy-associated acute massive airway hemorrhage had more serious impact on patients due to rapid bleeding, blurred vision of bronchoscopy, inability to stop bleeding quickly, blood filling alveoli, and serious impact on oxygenation of the lung lobes. Polyvinyl chloride single-lumen endotracheal intubation for lung isolation, with its characteristics of low difficulty, wide applicability and available in most hospitals, may reduce the intraoperative mortality of patients with bronchoscopy-associated acute massive airway hemorrhage. TRIAL REGISTRATION: Chinese Clinical Trial Registry on 13/03/2022. REGISTRATION NUMBER: ChiCTR2200057470.

Serum Bile Acid Profiles Improve Clinical Prediction of Nonalcoholic Fatty Liver in T2DM patients.

Background: The present study aimed to assess the ability of serum bile acid profiles to predict the development of nonalcoholic fatty liver (NAFL) in type 2 diabetes mellitus (T2DM) patients. Methods: Using targeted ultraperformance liquid chromatography (UPLC) coupled with triple quadrupole mass spectrometry (TQ/MS), we compared serum bile acid levels in T2DM patients with NAFL (n = 30) and age- and sex-matched T2DM patients without NAFL (n = 36) at the first time. Second, an independent cohort study of T2DM patients with NAFL (n = 17) and age- and sex-matched T2DM patients without NAFL (n = 20) was used to validate the results. The incremental benefits of serum biomarkers, clinical variables alone, or with biomarkers were then evaluated using receiver operating characteristic (ROC) curves and decision curve analysis. The area under the curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used to evaluate the biomarker predictive abilities. Results: The serum bile acid profiles in T2DM patients with NAFL were significantly different from T2DM patients without NAFL, as characterized by the significant elevation of LCA, TLCA, TUDCA, CDCA-24G, and TCDCA, which may be potential biomarkers for the identification of NAFL in T2DM patients. Based on the improvement in AUC, IDI, and NRI, the addition of 5 bile acids to a model with clinical variables statistically improved its predictive value. Similar results were found in the validation cohort. Conclusions: These results highlight that the detected biomarkers may contribute to the progression of NAFL in T2DM patients, and these biomarkers particularly in combination may help in the diagnosis of NAFL and allow earlier intervention in T2DM patients.

Ryanodine Receptors: A Potential Treatment Target in Various Neurodegenerative Disease.

Progressive neuronal demise is a key contributor to the key pathogenic event implicated in many different neurodegenerative disorders (NDDs). There are several therapeutic strategies available; however, none of them are particularly effective. Targeted neuroprotective therapy is one such therapy, which seems a compelling option, yet remains challenging due to the internal heterogeneity of the mechanisms underlying various NDDs. An alternative method to treat NDDs is to exploit common modalities involving molecularly distinct subtypes and thus develop specialized drugs with broad-spectrum characteristics. There is mounting evidence which supports for the theory that dysfunctional ryanodine receptors (RyRs) disrupt intracellular Ca2+ homeostasis, contributing to NDDs significantly. This review aims to provide direct and indirect evidence on the intersection of NDDs and RyRs malfunction, and to shed light on novel strategies to treat RyRs-mediated disease, modifying pharmacological therapies such as the potential therapeutic role of dantrolene, a RyRs antagonist.

Supraglottic jet oxygenation and ventilation reduces desaturation during bronchoscopy under moderate to deep sedation with propofol and remifentanil: A randomised controlled clinical trial.

BACKGROUND: Hypoxaemia is frequently seen during flexible bronchoscopies that are done with a nasal approach under the traditional sedation with propofol. This study investigated the potential benefits of supraglottic jet oxygenation and ventilation (SJOV) using the Wei nasal jet tube (WNJ) in reducing hypoxaemia in patients undergoing bronchoscopy under moderate to deep intravenous sedation using a propofol, lidocaine and remifentanil cocktail. OBJECTIVES: Our primary objective was to evaluate the efficacy and complications of SJOV via the WNJ during flexible bronchoscopy under moderate to heavy sedation with propofol and remifentanil. DESIGN: A randomised controlled clinical trial. SETTING: The 180th Hospital of People's Liberation Army, Quanzhou, China, from 1 June to 1 November 2019. PATIENTS: A total of 280 patients aged ≥18 years with American Society of Anesthesiologists' physical status 1 to 3 undergoing flexible bronchoscopy were studied. INTERVENTIONS: Patients were assigned randomly into one of two groups, a nasal cannula oxygenation (NCO) group (n = 140) using a nasal cannula to deliver oxygen (4 l min-1) or the SJOV group (n = 140) using a WNJ connected to a manual jet ventilator to provide SJOV at a driving pressure of 103 kPa, respiratory rate 20 min-1, FiO2 1.0 and inspiratory:expiratory (I:E) ratio 1:2. MAIN OUTCOME MEASURES: The primary outcome was an incidence of desaturation (defined as SpO2 < 90%) during the procedure. Other adverse events related to the sedation or SJOV were also recorded. RESULTS: Compared with the NCO group, the incidence of desaturation in the SJOV group was lower (NCO 37.0% vs. SJOV 13.1%) (P < 0.001). Patients in the SJOV group had a higher incidence of a dry mouth at 1 min (13.1% vs. 1.5%, P < 0.001) than at 30 min (1.5% vs. 0%, P = 0.159) or at 24 h (0% vs. 0%). There was no significant difference between the groups in respect of sore throat, subcutaneous emphysema or nasal bleeding. CONCLUSIONS: SJOV via a WNJ during flexible bronchoscopy under moderate to deep sedation with propofol and remifentanil significantly reduces the incidence of desaturation when compared with regular oxygen supplementation via a nasal cannula. Patients in the SJOV group had an increased incidence of transient dry mouth. TRIAL REGISTRATION: Registered at www.chictr.org.cn (ChiCTR1900023514).

Dantrolene Ameliorates Impaired Neurogenesis and Synaptogenesis in Induced Pluripotent Stem Cell Lines Derived from Patients with Alzheimer's Disease.

BACKGROUND: Overactivation of ryanodine receptors and the resulting impaired calcium homeostasis contribute to Alzheimer's disease-related pathophysiology. This study hypothesized that exposing neuronal progenitors derived from induced pluripotent stems cells of patients with Alzheimer's disease to dantrolene will increase survival, proliferation, neurogenesis, and synaptogenesis. METHODS: Induced pluripotent stem cells obtained from skin fibroblast of healthy subjects and patients with familial and sporadic Alzheimer's disease were used. Biochemical and immunohistochemical methods were applied to determine the effects of dantrolene on the viability, proliferation, differentiation, and calcium dynamics of these cells. RESULTS: Dantrolene promoted cell viability and proliferation in these two cell lines. Compared with the control, differentiation into basal forebrain cholinergic neurons significantly decreased by 10.7% (32.9 ± 3.6% vs. 22.2 ± 2.6%, N = 5, P = 0.004) and 9.2% (32.9 ± 3.6% vs. 23.7 ± 3.1%, N = 5, P = 0.017) in cell lines from sporadic and familial Alzheimer's patients, respectively, which were abolished by dantrolene. Synapse density was significantly decreased in cortical neurons generated from stem cells of sporadic Alzheimer's disease by 58.2% (237.0 ± 28.4 vs. 99.0 ± 16.6 arbitrary units, N = 4, P = 0.001) or familial Alzheimer's disease by 52.3% (237.0 ± 28.4 vs.113.0 ± 34.9 vs. arbitrary units, N = 5, P = 0.001), which was inhibited by dantrolene in the familial cell line. Compared with the control, adenosine triphosphate (30 µM) significantly increased higher peak elevation of cytosolic calcium concentrations in the cell line from sporadic Alzheimer's patients (84.1 ± 27.0% vs. 140.4 ± 40.2%, N = 5, P = 0.049), which was abolished by the pretreatment of dantrolene. Dantrolene inhibited the decrease of lysosomal vacuolar-type H-ATPase and the impairment of autophagy activity in these two cell lines from Alzheimer's disease patients. CONCLUSIONS: Dantrolene ameliorated the impairment of neurogenesis and synaptogenesis, in association with restoring intracellular Ca homeostasis and physiologic autophagy, cell survival, and proliferation in induced pluripotent stem cells and their derived neurons from sporadic and familial Alzheimer's disease patients.

Perioperative Neurocognitive Disorder: State of the Preclinical Science.

The purpose of this article is to provide a succinct summary of the different experimental approaches that have been used in preclinical postoperative cognitive dysfunction research, and an overview of the knowledge that has accrued. This is not intended to be a comprehensive review, but rather is intended to highlight how the many different approaches have contributed to our understanding of postoperative cognitive dysfunction, and to identify knowledge gaps to be filled by further research. The authors have organized this report by the level of experimental and systems complexity, starting with molecular and cellular approaches, then moving to intact invertebrates and vertebrate animal models. In addition, the authors' goal is to improve the quality and consistency of postoperative cognitive dysfunction and perioperative neurocognitive disorder research by promoting optimal study design, enhanced transparency, and "best practices" in experimental design and reporting to increase the likelihood of corroborating results. Thus, the authors conclude with general guidelines for designing, conducting and reporting perioperative neurocognitive disorder rodent research.

Emergency tracheal intubation in 202 patients with COVID-19 in Wuhan, China: lessons learnt and international expert recommendations.

Tracheal intubation in coronavirus disease 2019 (COVID-19) patients creates a risk to physiologically compromised patients and to attending healthcare providers. Clinical information on airway management and expert recommendations in these patients are urgently needed. By analysing a two-centre retrospective observational case series from Wuhan, China, a panel of international airway management experts discussed the results and formulated consensus recommendations for the management of tracheal intubation in COVID-19 patients. Of 202 COVID-19 patients undergoing emergency tracheal intubation, most were males (n=136; 67.3%) and aged 65 yr or more (n=128; 63.4%). Most patients (n=152; 75.2%) were hypoxaemic (Sao2 <90%) before intubation. Personal protective equipment was worn by all intubating healthcare workers. Rapid sequence induction (RSI) or modified RSI was used with an intubation success rate of 89.1% on the first attempt and 100% overall. Hypoxaemia (Sao2 <90%) was common during intubation (n=148; 73.3%). Hypotension (arterial pressure <90/60 mm Hg) occurred in 36 (17.8%) patients during and 45 (22.3%) after intubation with cardiac arrest in four (2.0%). Pneumothorax occurred in 12 (5.9%) patients and death within 24 h in 21 (10.4%). Up to 14 days post-procedure, there was no evidence of cross infection in the anaesthesiologists who intubated the COVID-19 patients. Based on clinical information and expert recommendation, we propose detailed planning, strategy, and methods for tracheal intubation in COVID-19 patients.

Propofol affects mouse embryonic fibroblast survival and proliferation in vitro via ATG5- and calcium-dependent regulation of autophagy.

Propofol is a commonly used intravenous anesthetic agent, which has been found to affect cell survival and proliferation especially in early life. Our previous studies show that propofol-induced neurodegeneration and neurogenesis are closely associated with cell autophagy. In the present study we explored the roles of autophagy-related gene 5 (ATG5) in propofol-induced autophagy in mouse embryonic fibroblasts (MEF) in vitro. We showed that ATG5 was functionally related to propofol-induced cell survival and damage: propofol significantly enhanced cell survival and proliferation at a clinically relevant dose (10 µM), but caused cell death at an extremely high concentration (200 µM) in ATG5-/- MEF, but not in WT cells. The dual effects found in ATG5-/- MEF could be blocked by intracellular Ca2+ channel antagonists. We also found that propofol evoked a moderate (promote cell growth) and extremely high (cause apoptosis) cytosolic Ca2+ elevation at the concentrations of 10 µM and 200 µM, respectively, only in ATG5-/- MEF. In addition, ATG5-/- MEF themselves released more Ca2+ in cytosolic space and endoplasmic reticulum compared with WT cells, suggesting that autophagy deficiency made intracellular calcium signaling more vulnerable to external stimuli (propofol). Altogether, our results reveal that ATG5 plays a crucial role in propofol regulation of cell survival and proliferation by affecting intracellular Ca2+ homeostasis.

Sevoflurane modulates breast cancer cell survival via modulation of intracellular calcium homeostasis.

BACKGROUND: Some retrospective and in vitro studies suggest that general anesthetics influence breast cancer recurrence and metastasis. We compared the effects of general anesthetics sevoflurane versus propofol on breast cancer cell survival, proliferation and invasion in vitro. The investigation focused on effects in intracellular Ca2+ homeostasis as a mechanism for general anesthetic-mediated effects on breast cancer cell survival and metastasis. METHODS: Estrogen receptor-positive (MCF7) and estrogen receptor-negative (MDA-MB-436) human breast cancer cell lines along with normal breast tissue (MCF10A) were used. Cells were exposed to sevoflurane or propofol at clinically relevant and extreme doses and durations for dose- and time-dependence studies. Cell survival, proliferation and migration following anesthetic exposure were assessed. Intracellular and extracellular Ca2+ concentrations were modulated using Ca2+ chelation and a TRPV1 Ca2+ channel antagonist to examine the role of Ca2+ in mediating anesthetic effects. RESULTS: Sevoflurane affected breast cancer cell survival in dose-, time- and cell type-dependent manners. Sevoflurane, but not propofol, at equipotent and clinically relevant doses (2% vs. 2 µM) for 6 h significantly promoted breast cell survival in all three types of cells. Paradoxically, extreme exposure to sevoflurane (4%, 24 h) decreased survival in all three cell lines. Chelation of cytosolic Ca2+ dramatically decreased cell survival in both breast cancer lines but not control cells. Inhibition of TRPV1 receptors significantly reduced cell survival in all cell types, an effect that was partially reversed by equipotent sevoflurane but not propofol. Six-hour exposure to sevoflurane or propofol did not affect cell proliferation, metastasis or TRPV1 protein expression in any type of cell. CONCLUSION: Sevoflurane, but not propofol, at clinically relevant concentrations and durations, increased survival of breast cancer cells in vitro but had no effect on cell proliferation, migration or TRPV1 expression. Breast cancer cells require higher cytoplasmic Ca2+ levels for survival than normal breast tissue. Sevoflurane affects breast cancer cell survival via modulation of intracellular Ca2+ homeostasis.

Supraglottic jet oxygenation and ventilation assisted fiberoptic intubation in a paralyzed patient with morbid obesity and obstructive sleep apnea: a case report.

BACKGROUND: Hypoxia is a major concern and cause of morbidity or mortality during tracheal intubation after anesthesia induction in a pathological obese patient with obstructive sleep apnea (OSA). We introduce a case using Supraglottic jet oxygenation and ventilation (SJOV) to promote oxygenation/ventilation during fiberoptic intubation in a paralyzed patient with morbid obesity and OSA. CASE PRESENTATION: A 46-year-old man weighting 176 kg with BMI 53.7 kg/m2 was scheduled for gastric volume reduction surgery to reduce body weight under general anesthesia. SpO2 decreased during induction, and two hand pressured mask ventilation partial failed. We then placed WEI Nasal Jet Tube (WNJ) in the patient's right nostril to provide SJOV. Then fiberoptic bronchoscopy guided endotracheal intubation was performed via mouth approach, and vital signs were stable. The operation was successfully completed after 3 h. Patient recovered smoothly in hospital for 8 days and did not have any recall inside the operating room. CONCLUSION: SJOV via WNJ could effectively maintain adequate oxygenation/ventilation during long time fiberoptic intubation in an apnea patient with morbid obesity and OSA after partial failure of two hand pressured mask ventilation, without obvious complications. This may provide a new effective approach for difficult airway management in these patients.

Supraglottic jet oxygenation and ventilation for obese patients under intravenous anesthesia during hysteroscopy: a randomized controlled clinical trial.

BACKGROUND: Supraglottic jet oxygenation and ventilation (SJOV) can effectively maintain adequate oxygenation in patients with respiratory depression, even in apnea patients. However, there have been no randomized controlled clinical trials of SJOV in obese patients. This study investigated the efficacy and safety of SJOV using WEI Nasal Jet tube (WNJ) for obese patients who underwent hysteroscopy under intravenous anesthesia without endotracheal intubation. METHODS: A single-center, prospective, randomized controlled study was conducted. The obese patients receiving hysteroscopy under intravenous anesthesia were randomly divided into three groups: Control group maintaining oxygen supply via face masks (100% oxygen, flow at 6 L/min), the WNJ Oxygen Group with WNJ (100% oxygen, flow: 6 L/min) and the WNJ SJOV Group with SJOV via WNJ [Jet ventilator working parameters:100% oxygen supply, driving pressure (DP) 0.1 MPa, respiratory rate; (RR): 15 bpm, I/E; ratio 1:1.5]. SpO2, PETCO2, BP, HR, ECG and BIS were continuously monitored during anesthesia. Two-Diameter Method was deployed to measure cross sectional area of the gastric antrum (CSA-GA) by ultrasound before and after SJOV in the WNJ SJOV Group. Episodes of SpO2 less than 95%, PETCO2 less than 10 mmHg, depth of WNJ placement and measured CSA-GA before and after jet ventilation in the WNJ SJOV Group during the operation were recorded. The other adverse events were collected as well. RESULTS: A total of 102 patients were enrolled, with two patients excluded. Demographic characteristics were similar among the three groups. Compared with the Control Group, the incidence of PETCO2 < 10 mmHg, SpO2 < 95% in the WNJ SJOV group dropped from 36 to 9% (P = 0.009),from 33 to 6% (P = 0.006) respectively,and the application rate of jaw-lift decreased from 33 to 3% (P = 0.001), and the total percentage of adverse events decreased from 36 to 12% (P = 0.004). Compared with the WNJ Oxygen Group, the use of SJOV via WNJ significantly decreased episodes of SpO2 < 95% from 27 to 6% (P = 0.023), PETCO2 < 10 mmHg from 33 to 9% (P = 0.017), respectively. Depth of WNJ placement was about 12.34 cm in WNJ SJOV Group. There was no significantly difference of CSA-GA before and after SJOV in the WNJ SJOV Group (P = 0.234). There were no obvious cases of nasal bleeding in all the three groups. CONCLUSIONS: SJOV can effectively and safely maintain adequate oxygenation in obese patients under intravenous anesthesia without intubation during hysteroscopy. This efficient oxygenation may be mainly attributed to supplies of high concentration oxygenation to the supraglottic area, and the high pressure jet pulse providing effective ventilation. Although the nasal airway tube supporting collapsed airway by WNJ also plays a role. SJOV doesn't seem to increase gastric distension and the risk of aspiration. SJOV can improve the safety of surgery by reducing the incidence of the intraoperative involuntary limbs swing, hip twist and cough. TRIAL REGISTRATION: Chinese Clinical Trial Registry. Registration number, ChiCTR1800017028, registered on July 9, 2018.

Best Practices for Postoperative Brain Health: Recommendations From the Fifth International Perioperative Neurotoxicity Working Group.

As part of the American Society of Anesthesiology Brain Health Initiative goal of improving perioperative brain health for older patients, over 30 experts met at the fifth International Perioperative Neurotoxicity Workshop in San Francisco, CA, in May 2016, to discuss best practices for optimizing perioperative brain health in older adults (ie, >65 years of age). The objective of this workshop was to discuss and develop consensus solutions to improve patient management and outcomes and to discuss what older adults should be told (and by whom) about postoperative brain health risks. Thus, the workshop was provider and patient oriented as well as solution focused rather than etiology focused. For those areas in which we determined that there were limited evidence-based recommendations, we identified knowledge gaps and the types of scientific knowledge and investigations needed to direct future best practice. Because concerns about perioperative neurocognitive injury in pediatric patients are already being addressed by the SmartTots initiative, our workshop discussion (and thus this article) focuses specifically on perioperative cognition in older adults. The 2 main perioperative cognitive disorders that have been studied to date are postoperative delirium and cognitive dysfunction. Postoperative delirium is a syndrome of fluctuating changes in attention and level of consciousness that occurs in 20%-40% of patients >60 years of age after major surgery and inpatient hospitalization. Many older surgical patients also develop postoperative cognitive deficits that typically last for weeks to months, thus referred to as postoperative cognitive dysfunction. Because of the heterogeneity of different tools and thresholds used to assess and define these disorders at varying points in time after anesthesia and surgery, a recent article has proposed a new recommended nomenclature for these perioperative neurocognitive disorders. Our discussion about this topic was organized around 4 key issues: preprocedure consent, preoperative cognitive assessment, intraoperative management, and postoperative follow-up. These 4 issues also form the structure of this document. Multiple viewpoints were presented by participants and discussed at this in-person meeting, and the overall group consensus from these discussions was then drafted by a smaller writing group (the 6 primary authors of this article) into this manuscript. Of course, further studies have appeared since the workshop, which the writing group has incorporated where appropriate. All participants from this in-person meeting then had the opportunity to review, edit, and approve this final manuscript; 1 participant did not approve the final manuscript and asked for his/her name to be removed.

Propofol Affects Neurodegeneration and Neurogenesis by Regulation of Autophagy via Effects on Intracellular Calcium Homeostasis.

BACKGROUND: In human cortical neural progenitor cells, we investigated the effects of propofol on calcium homeostasis in both the ryanodine and inositol 1,4,5-trisphosphate calcium release channels. We also studied propofol-mediated effects on autophagy, cell survival, and neuro- and gliogenesis. METHODS: The dose-response relationship between propofol concentration and duration was studied in neural progenitor cells. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase release assays. The effects of propofol on cytosolic calcium concentration were evaluated using Fura-2, and autophagy activity was determined by LC3II expression levels with Western blot. Proliferation and differentiation were evaluated by bromodeoxyuridine incorporation and immunostaining with neuronal and glial markers. RESULTS: Propofol dose- and time-dependently induced cell damage and elevated LC3II expression, most robustly at 200 µM for 24 h (67 ± 11% of control, n = 12 to 19) and 6 h (2.4 ± 0.5 compared with 0.6 ± 0.1 of control, n = 7), respectively. Treatment with 200 µM propofol also increased cytosolic calcium concentration (346 ± 71% of control, n = 22 to 34). Propofol at 10 µM stimulated neural progenitor cell proliferation and promoted neuronal cell fate, whereas propofol at 200 µM impaired neuronal proliferation and promoted glial cell fate (n = 12 to 20). Cotreatment with ryanodine and inositol 1,4,5-trisphosphate receptor antagonists and inhibitors, cytosolic Ca chelators, or autophagy inhibitors mostly mitigated the propofol-mediated effects on survival, proliferation, and differentiation. CONCLUSIONS: These results suggest that propofol-mediated cell survival or neurogenesis is closely associated with propofol's effects on autophagy by activation of ryanodine and inositol 1,4,5-trisphosphate receptors.

Supraglottic jet oxygenation and ventilation saved a patient with 'cannot intubate and cannot ventilate' emergency difficult airway.

The emergency difficult airway with the 'cannot intubate and cannot ventilate' (CICV) situation contributes to a high percentage of anesthesia- and emergency medicine-related morbidity and mortality. A new technique of supraglottic jet oxygenation and ventilation (SJOV) via the nasal approach was successfully used in an emergency to save a patient with a CICV difficult airway from a catastrophic outcome.

ASPP2 suppresses stem cell-like characteristics and chemoresistance by inhibiting the Src/FAK/Snail axis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of death in cancer patients worldwide. Understanding the molecular pathogenesis of HCC recurrence and chemoresistance is key to improving patients' prognosis. In this study, we report that downregulation of ASPP2, a member of the ankyrin-repeat-containing, SH3-domain-containing, and proline-rich-region-containing protein (ASPP) family, bestowed HCC cells with stem-like properties and resistance to chemotherapy, including the expansion of side population fractions, formation of hepatospheroids, expression of stem cell-associated genes, loss of chemosensitivity, and increased tumorigenicity in immunodeficient mice. An expression profiling assay revealed that ASPP2 specifically repressed focal adhesion kinase (FAK)/Src/extracellular signal regulated kinase (ERK) signaling. ASPP2 does this by physically interacting with C-terminal Src kinase (CSK) and stimulating its kinase activity, which eventually leads to activator protein 1 (AP1)-mediated downregulation of Snail expression. In addition, pharmacologic inhibition of Src attenuated the effects of ASPP2 deficiency. Our findings present functional and mechanistic insight into the critical role of ASPP2 in the inhibition of HCC stemness and drug resistance and may provide a new strategy for therapeutic combinations to treat HCC.

Myeloid-derived suppressor cells regulate immune response in patients with chronic hepatitis B virus infection through PD-1-induced IL-10.

Although myeloid-derived suppressor cells (MDSCs) are well known for their immunosuppressive function in several pathological conditions, the role of MDSCs in hepatitis B virus infection remains obscure. In this study, we investigated the frequency and function of MDSCs in the peripheral blood and liver of 91 chronic hepatitis B (CHB) patients. A higher percentage of MDSCs, defined as CD14(+)HLA-DR(-/low), was detected in peripheral blood of CHB patients than that of the healthy controls. Moreover, high expression of programmed death 1 (PD-1) and secretion of IL-10 in this population were determined. The frequency of MDSCs was positively correlated with serum viral load, but it was negatively correlated with liver inflammatory injury. These cells were also abundant in liver tissue of CHB patients and were related to necroinflammatory activity. Furthermore, we found that these cells could suppress hepatitis B virus-specific CD8(+) T cell response, including reduced proliferation and IFN-γ production, and inhibit degranulation of CD8(+) T cells, including reduced production of granzyme B and perforin. Importantly, PD-1-induced IL-10 production by MDSCs was responsible for the suppressive activity. To our knowledge, for the first time our study proved that CD14(+)HLA-DR(-/low)PD-1(+) MDSCs in CHB patients contribute to an inadequate immune response against the virus and lead to chronic infection, which represents a potential target for therapeutic intervention.