Development of nanogap-rich hybrid gold nanostructures by use of two non-lithographic deposition techniques for a sensitive and reliable SERS biosensor.

Practical application of surface-enhanced Raman spectroscopy (SERS) has suffered from several limitations by heterogeneous distribution of hot-spots, such as high signal fluctuation and the resulting low reliability in detection. Herein, we develop a strategy of more sensitive and reliable SERS platform through designing spatially homogeneous gold nanoparticles (GNPs) on a uniform gold nanoisland (GNI) pattern. The proposed SERS substrate is successfully fabricated by combining two non-lithographic techniques of electron beam evaporation and convective self-assembly. These bottom-up methods allow a simple, cost-effective, and large-area fabrication. Compared to the SERS substrates obtained from two separate nanofabrication methods, Raman spectra measured by the samples with both GNPs and GNIs present a significant increase in the signal intensity as well as a notable improvement in signal fluctuation. The simulated near-field analyses demonstrate the formation of highly amplified plasmon modes within and at the gaps of the GNP-GNI interfaces. Moreover, the suggested SERS sensor is evaluated to detect the glucose concentration, exhibiting that the detection sensitivity is improved by more than 10 times compared to the sample with only GNI patterns and a fairly good spatial reproducibility of 7% is accomplished. It is believed that our suggestion could provide a potential for highly sensitive, low-cost, and reliable SERS biosensing platforms that include many advantages for healthcare devices. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-024-00381-4.

Atractylodes macrocephala Koidz Alleviates Symptoms in Zymosan-Induced Irritable Bowel Syndrome Mouse Model through TRPV1, NaV1.5, and NaV1.7 Channel Modulation.

(1) Background: Irritable bowel syndrome (IBS) is a common disease in the gastrointestinal (GI) tract. Atractylodes macrocephala Koidz (AMK) is known as one of the traditional medicines that shows a good efficacy in the GI tract. (2) Methods: We investigated the effect of AMK in a network pharmacology and zymosan-induced IBS animal model. In addition, we performed electrophysiological experiments to confirm the regulatory mechanisms related to IBS. (3) Results: Various characteristics of AMK were investigated using TCMSP data and various analysis systems. AMK restored the macroscopic changes and weight to normal. Colonic mucosa and inflammatory factors were reduced. These effects were similar to those of amitriptyline and sulfasalazine. In addition, transient receptor potential (TRP) V1, voltage-gated Na+ (NaV) 1.5, and NaV1.7 channels were inhibited. (4) Conclusion: These results suggest that AMK may be a promising therapeutic candidate for IBS management through the regulation of ion channels.

Does coronavirus disease 2019 history alone increase the risk of postoperative pulmonary complications after surgery? Prospective observational study using serology assessment.

BACKGROUND: Concern exists about the increasing risk of postoperative pulmonary complications in patients with a history of coronavirus disease 2019 (COVID-19). OBJECTIVE: We conducted a prospective observational study that compared the incidence of postoperative pulmonary complications in patients with and without a history of COVID-19. METHODS: From August 2022 to November 2022, 244 adult patients undergoing major non-cardiac surgery were enrolled and allocated either to history or no history of COVID-19 groups. For patients without a history of confirming COVID-19 diagnosis, we tested immunoglobulin G to nucleocapsid antigen of SARS-CoV-2 for serology assessment to identify undetected infection. We compared the incidence of postoperative pulmonary complications, defined as a composite of atelectasis, pleural effusion, pulmonary edema, pneumonia, aspiration pneumonitis, and the need for additional oxygen therapy according to a COVID-19 history. RESULTS: After excluding 44 patients without a COVID-19 history who were detected as seropositive, 200 patients were finally enrolled in this study, 100 in each group. All subjects with a COVID-19 history experienced no or mild symptoms during infection. The risk of postoperative pulmonary complications was not significantly different between the groups according to the history of COVID-19 (24.0% vs. 26.0%; odds ratio, 0.99; 95% confidence interval, 0.71-1.37; P-value, 0.92). The incidence of postoperative pulmonary complications was also similar (27.3%) in excluded patients owing to being seropositive. CONCLUSION: Our study showed patients with a history of no or mild symptomatic COVID-19 did not show an increased risk of PPCs compared to those without a COVID-19 history. Additional precautions may not be needed to prevent PPCs in those patients.

Preoperative C-reactive protein/albumin ratio and mortality of off-pump coronary artery bypass graft.

Background: We sought to investigate the prognostic value of preoperative C-reactive protein (CRP)-to-albumin ratio (CAR) for the prediction of mortality in patients undergoing off-pump coronary artery bypass grafting (OPCAB). Methods: From January 2010 to August 2016, adult patients undergoing OPCAB were analyzed retrospectively. In a total of 2,082 patients, preoperative inflammatory markers including CAR, CRP, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were recorded. Receiver operating characteristic (ROC) curves were used to determine the optimal threshold and compare the predictive values of the markers. The patients were divided into two groups according to the cut-off value of CAR, and then the outcomes were compared. The primary end point was 1-year mortality. Results: During the 1-year follow-up period, 25 patients (1.2%) died after OPCAB. The area under the curve of CAR for 1-year mortality was 0.767, which was significantly higher than other inflammatory markers. According to the calculated cut-off value of 1.326, the patients were divided into two groups: 1,580 (75.9%) patients were placed in the low CAR group vs. 502 (24.1%) patients in the high CAR group. After adjustment with inverse probability weighting, high CAR was significantly associated with increased risk of 1-year mortality after OPCAB (Hazard ratio, 5.01; 95% Confidence interval, 2.01-12.50; p < 0.001). Conclusions: In this study, we demonstrated that preoperative CAR was associated with 1-year mortality following OPCAB. Compared to previous inflammatory markers, CAR may offer superior predictive power for mortality in patients undergoing OPCAB. For validation of our findings, further prospective studies are needed.

Use of functional magnetic resonance imaging to identify cortical loci for lower limb movements and their efficacy for individuals after stroke.

BACKGROUND: Identification of cortical loci for lower limb movements for stroke rehabilitation is crucial for better rehabilitation outcomes via noninvasive brain stimulation by targeting the fine-grained cortical loci of the movements. However, identification of the cortical loci for lower limb movements using functional MRI (fMRI) is challenging due to head motion and difficulty in isolating different types of movement. Therefore, we developed a custom-made MR-compatible footplate and leg cushion to identify the cortical loci for lower limb movements and conducted multivariate analysis on the fMRI data. We evaluated the validity of the identified loci using both fMRI and behavioral data, obtained from healthy participants as well as individuals after stroke. METHODS: We recruited 33 healthy participants who performed four different lower limb movements (ankle dorsiflexion, ankle rotation, knee extension, and toe flexion) using our custom-built equipment while fMRI data were acquired. A subgroup of these participants (Dataset 1; n = 21) was used to identify the cortical loci associated with each lower limb movement in the paracentral lobule (PCL) using multivoxel pattern analysis and representational similarity analysis. The identified cortical loci were then evaluated using the remaining healthy participants (Dataset 2; n = 11), for whom the laterality index (LI) was calculated for each lower limb movement using the cortical loci identified for the left and right lower limbs. In addition, we acquired a dataset from 15 individuals with chronic stroke for regression analysis using the LI and the Fugl-Meyer Assessment (FMA) scale. RESULTS: The cortical loci associated with the lower limb movements were hierarchically organized in the medial wall of the PCL following the cortical homunculus. The LI was clearer using the identified cortical loci than using the PCL. The healthy participants (mean ± standard deviation: 0.12 ± 0.30; range: - 0.63 to 0.91) exhibited a higher contralateral LI than the individuals after stroke (0.07 ± 0.47; - 0.83 to 0.97). The corresponding LI scores for individuals after stroke showed a significant positive correlation with the FMA scale for paretic side movement in ankle dorsiflexion (R2 = 0.33, p = 0.025) and toe flexion (R2 = 0.37, p = 0.016). CONCLUSIONS: The cortical loci associated with lower limb movements in the PCL identified in healthy participants were validated using independent groups of healthy participants and individuals after stroke. Our findings suggest that these cortical loci may be beneficial for the neurorehabilitation of lower limb movement in individuals after stroke, such as in developing effective rehabilitation interventions guided by the LI scores obtained for neuronal activations calculated from the identified cortical loci across the paretic and non-paretic sides of the brain.

A Compact Memristor Model Based on Physics-Informed Neural Networks.

Memristor devices have diverse physical models depending on their structure. In addition, the physical properties of memristors are described using complex differential equations. Therefore, it is necessary to integrate the various models of memristor into an unified physics-based model. In this paper, we propose a physics-informed neural network (PINN)-based compact memristor model. PINNs can solve complex differential equations intuitively and with ease. This methodology is used to conduct memristor physical analysis. The weight and bias extracted from the PINN are implemented in a Verilog-A circuit simulator to predict memristor device characteristics. The accuracy of the proposed model is verified using two memristor devices. The results show that PINNs can be used to extensively integrate memristor device models.

Association between Preoperative Glucose Dysregulation and Delirium after Non-Cardiac Surgery.

This study aimed to investigate the association between glucose dysregulation and delirium after non-cardiac surgery. Among a total of 203,787 patients who underwent non-cardiac surgery between January 2011 and June 2019 at our institution, we selected 61,805 with available preoperative blood glucose levels within 24 h before surgery. Patients experiencing glucose dysregulation were divided into three groups: hyperglycemia, hypoglycemia, and both. We compared the incidence of postoperative delirium within 30 days after surgery between exposed and unexposed patients according to the type of glucose dysregulation. The overall incidence of hyperglycemia, hypoglycemia, and both was 5851 (9.5%), 1452 (2.3%), and 145 (0.2%), respectively. The rate of delirium per 100 person-months of the exposed group was higher than that of the unexposed group in all types of glucose dysregulation. After adjustment, the hazard ratios of glucose dysregulation in the development of delirium were 1.35 (95% CI, 1.18-1.56) in hyperglycemia, 1.36 (95% CI, 1.06-1.75) in hypoglycemia, and 3.14 (95% CI, 1.27-7.77) in both. The subgroup analysis showed that exposure to hypoglycemia or both to hypo- and hyperglycemia was not associated with delirium in diabetic patients, but hyperglycemia was consistently associated with postoperative delirium regardless of the presence of diabetes. Preoperative glucose dysregulation was associated with increased risk of delirium after non-cardiac surgery. Our findings may be helpful for preventing postoperative delirium, and further investigations are required to verify the association and mechanisms for the effect we observed.

Association of preoperative blood glucose level with delirium after non-cardiac surgery in diabetic patients.

BACKGROUND: Hyperglycemia has shown a negative association with cognitive dysfunction. We analyzed patients with high preoperative blood glucose level and hemoglobin A1c (HbA1c) level to determine the prevalence of postoperative delirium. METHODS: We reviewed a database of 23,532 patients with diabetes who underwent non-cardiac surgery. Acute hyperglycemia was defined as fasting blood glucose > 140 mg/dl or random glucose > 180 mg/dl within 24 h before surgery. Chronic hyperglycemia was defined as HbA1c level above 6.5% within three months before surgery. The incidence of delirium was compared according to the presence of acute and chronic hyperglycemia. RESULTS: Of the 23,532 diabetic patients, 21,585 had available preoperative blood glucose level within 24 h before surgery, and 18,452 patients reported levels indicating acute hyperglycemia. Of the 8,927 patients with available HbA1c level within three months before surgery, 5,522 had levels indicating chronic hyperglycemia. After adjustment with inverse probability weighting, acute hyperglycemia was related to higher incidence of delirium (hazard ratio: 1.33, 95% CI [1.10,1.62], P = 0.004 for delirium) compared with controls without acute hyperglycemia. On the other hand, chronic hyperglycemia did not correlate with postoperative delirium. CONCLUSIONS: Preoperative acute hyperglycemia was associated with postoperative delirium, whereas chronic hyperglycemia was not significantly associated with postoperative delirium. Irrespective of chronic hyperglycemia, acute glycemic control in surgical patients could be crucial for preventing postoperative delirium.

Anesthetic management for non-cardiac surgery in patients with left ventricular assist devices.

With the growing number of patients undergoing left ventricular assist device (LVAD) implantation and improved survival in this population, more patients with LVADs are presenting for various types of non-cardiac surgery. Therefore, anesthesiologists need to understand the physiology and adequately prepare for the perioperative management of this unique patient population. This review addresses perioperative considerations and intraoperative management for the safe and successful management of patients with an LVAD undergoing non-cardiac surgery. Understanding the basic physiology of preload dependency and afterload sensitivity in these patients is essential. The main considerations include a collaborative preoperative multidisciplinary approach, perioperative care aimed at optimizing the intravascular volume and right ventricular function, and maintaining the afterload within recommended ranges for optimal LVAD function.

Perioperative adverse cardiac events and mortality after non-cardiac surgery: a multicenter study.

BACKGROUND: Perioperative adverse cardiac events (PACE), a composite of myocardial infarction, coronary revascularization, congestive heart failure, arrhythmic attack, acute pulmonary embolism, cardiac arrest, and stroke during 30-day postoperative period, is associated with long-term mortality, but with limited clinical evidence. We compared long-term mortality with PACE using data from nationwide multicenter electronic health records. METHODS: Data from 7 hospitals, converted to Observational Medical Outcomes Partnership Common Data Model, were used. We extracted records of 277,787 adult patients over 18 years old undergoing non-cardiac surgery for the first time at the hospital and had medical records for more than 180 days before surgery. We performed propensity score matching and then an aggregated meta­analysis. RESULTS: After 1:4 propensity score matching, 7,970 patients with PACE and 28,807 patients without PACE were matched. The meta­analysis showed that PACE was associated with higher one-year mortality risk (hazard ratio [HR]: 1.33, 95% CI [1.10, 1.60], P = 0.005) and higher three-year mortality (HR: 1.18, 95% CI [1.01, 1.38], P = 0.038). In subgroup analysis, the risk of one-year mortality by PACE became greater with higher-risk surgical procedures (HR: 1.20, 95% CI [1.04, 1.39], P = 0.020 for low-risk surgery; HR: 1.69, 95% CI [1.45, 1.96], P < 0.001 for intermediate-risk; and HR: 2.38, 95% CI [1.47, 3.86], P = 0.034 for high-risk). CONCLUSIONS: A nationwide multicenter study showed that PACE was significantly associated with increased one-year mortality. This association was stronger in high-risk surgery, older, male, and chronic kidney disease subgroups. Further studies to improve mortality associated with PACE are needed.

Discovering individual fingerprints in resting-state functional connectivity using deep neural networks.

Non-negligible idiosyncrasy due to interindividual differences is an ongoing issue in resting-state functional MRI (rfMRI) analysis. We show that a deep neural network (DNN) can be employed for individual identification by learning important features from the time-varying functional connectivity (FC) of rfMRI in the Human Connectome Project. We employed the trained DNN to identify individuals from an independent dataset acquired at our institution. The results revealed that the DNN could successfully identify 300 individuals with an error rate of 2.9% using 15 s time-window and 870 individuals with an error rate of 6.7%. A trained DNN with nonlinear hidden layers led to the proposal of the "fingerprint of FC" (fpFC) as representative edges of individual FC. The fpFCs for individuals exhibited commonly important and individual-specific edges across time-window lengths (from 5 min to 15 s). Furthermore, the utility of our model for another group of subjects was validated, supporting the feasibility of our technique in the context of transfer learning. In conclusion, our study offers an insight into the discovery of the intrinsic mode of the human brain using whole-brain resting-state FC and DNNs.

Effect of Repeated Greater Occipital Nerve Block in Patients with Ocular Neuropathic Pain: A Retrospective Observational Study.

Ocular neuropathic pain (ONP) has various etiologies, and patients have various symptoms. The clinical management of patients with ONP has been debated. We aimed to evaluate the effect of repeated greater occipital nerve block (GONB) on ONP based on convergence in the trigeminocervical complex. In this single-center retrospective study, the medical records of 204 patients who were referred to the pain clinic by the ophthalmology department of our hospital and subsequently underwent repeated GONB for chronic ONP between January 2008 and February 2022 were analyzed. They received GONB every two weeks, up to 10 times. Symptoms of ONP were divided into five categories: eye pain, dysesthesias/allodynia, non-eye pain, visual disturbance, and tearing. The primary outcome of this study was the pain relief scale (PRS) score after repeated injections. The differences and magnitude of decrease in the overall pain relief scale score were statistically significant (estimate = -0.55, p < 0.001). There were two patients who had recurrence of ONP and seven patients who had adverse events. According to our study, repeated GONB can reduce symptom severity in patients with ONP. Therefore, it appears that GONB can be considered a multimodal management method for ONP.

Outcomes of open repair for descending thoracic and thoracoabdominal aortic aneurysm in recent 10 years: experience of a high-volume centre in Korea.

OBJECTIVES: Although recent studies and guidelines suggest the preferred outcomes after surgical repair of thoracic aortic aneurysm (TAA) and thoracoabdominal aortic aneurysm (TAAA), published results are limited to those from high-volume hospitals and based on old data gathered before optimal management was established. Here, we analysed our outcomes over the previous 10 years from cases of open TAA and TAAA repair to offer updated and real-world results of those complex procedures performed in a high-volume centre. METHODS: From November 2013 to April 2022, 212 consecutive adult patients who underwent open TAA and TAAA repair were enrolled. We analysed early and late outcomes after surgery, including postoperative complications and mortality. RESULTS: There were 154 (73%) men, and the median age at surgery was 61 years. Intraoperative death occurred in 1 patient due to uncontrolled bleeding. Nine patients (4%) died during follow-up, and the survival estimates at 5 years were 94 ± 3% and 95 ± 3% after descending TAA and TAAA repair, respectively. Ten patients (4%) suffered from spinal cord ischaemic injury (9 with paraplegia and 1 with paresthesia), but permanent paraplegia persisted in only 1 case. CONCLUSIONS: We report very low postoperative complication rates and excellent early and late survival rates after open TAA and TAAA repair from our recent 10-year data analysis. These findings may assist when choosing treatment options for these complicated diseases.

Evaluation of the Solidification of Radioactive Wastes Using Blast Furnace Slag as a Solidifying Agent.

The decommissioning process of nuclear power facilities renders hundreds of thousands of tons of various types of waste. Of these different waste types, the amount of concrete waste (CW) varies greatly depending on the type of facility, operating history, and regulation standards. From the previous decommissioning projects, CW was estimated to comprise 60-80 wt.% of the total weight of radioactive wastes. This represents a significant technical challenge to any decommissioning project. Furthermore, the disposal costs for the generated concrete wastes are a substantial part of the total budget for any decommissioning project. Thus, the development of technologies effective for the reduction and recycling of CW has become an urgent agenda globally. Blast furnace slag (BFS) is an industrial byproduct containing a sufficient amount (higher than 30%) of CaO and it can be used as a substitute for ordinary Portland cement (OPC). However, there have been few studies on the application of BFS for the treatment of radioactive waste from decommissioning processes. This study was conducted to evaluate the performance of the solidification agent using ground granulated BFS (SABFS) to pack radioactive wastes, such as the coarse aggregates of CW (CACW), waste soil (WS), and metal waste (MW). The analytical results indicated that the CaO content of the ground granulated BFS was 36.8% and it was confirmed that calcium silicate hydrate (CSH) could be activated as the precursor of the hydration reactions. In addition, the optimum water-to-binder ratio was determined to be 0.25 and Ca(OH)2 and CaSO4 were found to be the most effective alkaline and sulfate activators for improving the compressive strength of the SABFS. The maximum packing capacities of the SABFS were determined to be 9 and 13 wt.% for WC and WM, respectively, when the content of CW was fixed at 50 wt.%. The results of the leaching tests using SABFS containing radioactive wastes contaminated with Co, Cs, and Sr indicated that their leachability indices met the acceptance level for disposal. Consequently, the SABFS can be used as a solidifying agent for the safe disposal of radioactive waste.

Risk of age older than 65 years for 30-day cardiac complication may be comparable to low-to-moderate risk according to revised cardiac risk index in non-cardiac surgery.

Revised cardiac risk index (RCRI) is widely used for surgical patients without containing age as a risk factor. We investigated age older than 65 years with respect to low-to-moderate risk of RCRI. From January 2011 to June 2019, a total of 203,787 consecutive adult patients underwent non-cardiac surgery at our institution. After excluding high-risk patients defined as RCRI score > 2, we stratified the patients into four groups according to RCRI and age (A: age < 65 with RCRI < 2, [n = 148,288], B: age ≥ 65 with RCRI < 2, [n = 42,841], C: age < 65 with RCRI = 2, [n = 5,271], and D: age ≥ 65 with RCRI = 2, [n = 5,698]). Incidence of major cardiac complication defined as a composite of cardiac death, cardiac arrest and myocardial infarction was compared. After excluding 1,689 patients with high risk (defined as RCRI score > 2), 202,098 patients were enrolled. The incidence with 95% confidence interval of major cardiac complication for A, B, C, and D groups was 0.3% (0.2-0.3), 1.1% (1.0-1.2), 1.8% (1.6-1.8), and 3.1% (2.6-3.6), respectively. In a direct comparison between B and C groups, old patients with RCRI < 2 showed a significantly lower risk compared to younger patients with RCRI = 2 (odd ratio, 0.62; 95% confidence interval, 0.50-0.78; p < 0.001). In non-cardiac surgery, the risk of age older than 65 years was shown to be comparable with low-to-moderate risk according to RCRI.

Predictors of fluid responsiveness in the operating room: a narrative review.

Prediction of fluid responsiveness has been considered an essential tool for modern fluid management. However, most studies in this field have focused on patients in intensive care unit despite numerous research throughout several decades. Therefore, the present narrative review aims to show the representative method's feasibility, advantages, and limitations in predicting fluid responsiveness, focusing on the operating room environments. Firstly, we described the predictors of fluid responsiveness based on heart-lung interaction, including pulse pressure and stroke volume variations, the measurement of respiratory variations of inferior vena cava diameter, and the end-expiratory occlusion test and addressed their limitations. Subsequently, the passive leg raising test and mini-fluid challenge tests were also mentioned, which assess fluid responsiveness by mimicking a classic fluid challenge. In the last part of this review, we pointed out the pitfalls of fluid management based on fluid responsiveness prediction, which emphasized the importance of individualized decision-making. Understanding the available representative methods to predict fluid responsiveness and their associated benefits and drawbacks through this review will aid anesthesiologists in choosing the most reliable methods for optimal fluid administration in each patient during anesthesia in the operating room.

Autoencoder and restricted Boltzmann machine for transfer learning in functional magnetic resonance imaging task classification.

Deep neural networks (DNNs) have been adopted widely as classifiers for functional magnetic resonance imaging (fMRI) data, advancing beyond traditional machine learning models. Consequently, transfer learning of the pre-trained DNN becomes crucial to enhance DNN classification performance, specifically by alleviating an overfitting issue that occurs when a substantial number of DNN parameters are fitted to a relatively small number of fMRI samples. In this study, we first systematically compared the two most popularly used, unsupervised pretraining models for resting-state fMRI (rfMRI) volume data to pre-train the DNNs, namely autoencoder (AE) and restricted Boltzmann machine (RBM). The group in-brain mask used when training AE and RBM displayed a sizable overlap ratio with Yeo's seven functional brain networks (FNs). The parcellated FNs obtained from the RBM were fine-grained compared to those from the AE. The pre-trained AE and RBM served as the weight parameters of the first of the two hidden DNN layers, and the DNN fulfilled the task classifier role for fMRI (tfMRI) data in the Human Connectome Project (HCP). We tested two transfer learning schemes: (1) fixing and (2) fine-tuning the DNN's pre-trained AE or RBM weights. The DNN with transfer learning was compared to a baseline DNN, trained using random initial weights. Overall, DNN classification performance from the transfer learning proved superior when the pre-trained RBM weights were fixed and when the pre-trained AE weights were fine-tuned (average error rates: 14.8% for fixed RBM, 15.1% fine-tuned AE, and 15.5% for the baseline model) compared to the alternative scenarios of DNN transfer learning schemes. Moreover, the optimal transfer learning scheme between the fixed RBM and fine-tuned AE varied according to seven task conditions in the HCP. Nonetheless, the computational load reduced substantially for the fixed-weight-based transfer learning compared to the fine-tuning-based transfer learning (e.g., the number of weight parameters for the fixed-weight-based DNN model reduced to 1.9% compared with a baseline/fine-tuned DNN model). Our findings suggest that weight initialization at the DNN's first layer using RBM-based pre-trained weights provides the most promising approach when the whole-brain fMRI volume supports associated task classification. We believe that our proposed scheme could be applied to a variety of task conditions to improve their classification performance and to utilize computational resources efficiently using our AE/RBM-based pre-trained weights compared to random initial weights for DNN training.

A Comparative Inflammation-on-a-Chip with a Complete 3D Interface: Pharmacological Applications in COPD-Induced Neutrophil Migration.

Chronic obstructive pulmonary disease (COPD) is a slow-progressing inflammatory lung disease that is associated with high mortality and disability. There is a lack of appropriate preclinical models of COPD, which hampers drug discovery efforts. Herein, a comparative inflammation-on-a-chip (IoC) is developed with a complete 3D interface without the formation of any micropillar and phaseguide structures that replicated chemoattractant-induced neutrophil transendothelial migration (NTEM), a key feature of COPD. The IoC model is used to evaluate the pharmacological effects of CXCR2 inhibitors (MK-7123, AZD5069, and SB225002) on the migration of neutrophil-like cells in the presence of plasma samples from patients with COPD. This is the first study to evaluate inhibitors of CXCR2-dependent NTEM in a comparative IoC model that mimics the physiological 3D microenvironment, consisting of an endothelial barrier, extracellular compartment, and inflammatory conditions. This IoC model will be useful to investigate COPD severity using patient samples, and will aid basic and translational research involving NTEM.

Comparison of propofol vs. remimazolam on emergence profiles after general anesthesia: A randomized clinical trial.

STUDY OBJECTIVE: The emergence profiles in patients undergoing total intravenous anesthesia with either propofol or remimazolam with flumazenil reversal were compared. DESIGN: A prospective, double-blind, randomized trial. SETTING: An operating room and a post-anesthesia care unit (PACU). PATIENTS: Adult patients (n = 100) having American Society of Anesthesiologists (ASA) physical status of I-III undergoing general anesthesia were enrolled and randomly assigned to the propofol or the remimazolam group. INTERVENTIONS: The propofol group received target-controlled infusion of propofol, and the remimazolam group received continuous infusion of remimazolam. Continuous infusion of remifentanil was used in both groups. For emergence, flumazenil was used in increments of 0.2 mg in the remimazolam group. MEASUREMENTS: The primary outcome was the time required for the patient to obey verbal commands. The secondary outcomes included the time to bispectral index (BIS) over 80, the time to laryngeal mask airway (LMA) removal, the Richmond Agitation-Sedation Scale (RASS) scores in the PACU, and adverse events throughout the study period. MAIN RESULTS: The time taken to obey verbal commands was significantly longer in the propofol group than the remimazolam group (14 [9, 19]) vs. 5 [3, 7]) minutes, P < 0.001; median difference -9, 95% confidence interval -11 to -6). The times to BIS over 80 and to LMA removal were also significantly longer in the propofol group. In addition, the RASS score upon arrival to the PACU differed significantly between the two groups (P = 0.006). Re-sedation in the PACU was observed in 11 (22%) of the patients in the remimazolam group. CONCLUSIONS: Remimazolam-based total intravenous anesthesia with flumazenil reversal may be effective in reducing emergence time, but a significant incidence of re-sedation was observed in the PACU. Further studies are needed to determine adequate dose and timing of routine flumazenil use and minimize the risk of re-sedation.