Changes in oxygen supply-demand balance during induction of general anesthesia: an exploratory study using remimazolam.

PURPOSE: This study was performed to evaluate the changes in oxygen supply-demand balance during induction of general anesthesia using an indirect calorimeter capable of measuring oxygen consumption (VO2) and carbon dioxide production (VCO2). METHODS: This study included patients scheduled for surgery in whom remimazolam was administered as a general anesthetic. VO2 and VCO2 were measured at different intervals: upon awakening (T1), 15 min after tracheal intubation (T2), and 1 h after T2 (T3). Oxygen delivery (DO2) was calculated simultaneously with these measurements. VO2 was ascertained using an indirect calorimeter and further calculated using vital signs, among other factors. DO2 was derived from cardiac output and arterial blood gas analysis performed with an arterial pressure-based cardiac output measurement system. RESULTS: VO2, VCO2, and DO2 decreased significantly from T1 to T2 and T3 [VO2/body surface area (BSA) (ml/min/m2): T1, 130 (122-146); T2, 107 (83-139); T3, 97 (93-121); p = 0.011], [VCO2/BSA (ml/min/m2): T1, 115 (105-129); T2, 90 (71-107); T3, 81 (69-101); p = 0.011], [DO2/BSA (ml/min/m2): T1, 467 (395-582); T2, 347 (286-392); T3, 382 (238-414); p = 0.0020]. Among the study subjects, a subset exhibited minimal reduction in VCO2. Although the respiratory frequency was titrated on the basis of end-tidal CO2 levels, there was no significant difference between the groups. CONCLUSION: General anesthetic induction with remimazolam decreased VO2, VCO2, and DO2.

Risk factors indicating immune-related adverse events with combination chemotherapy with immune checkpoint inhibitors and platinum agents in patients with non-small cell lung cancer: a multicenter retrospective study.

PURPOSE: Immune checkpoint inhibitors (ICI) ushered in a new era for the treatment of non-small cell lung cancer (NSCLC). However, they carry the risk of immune-related adverse events (irAEs). Recently, various studies have been conducted on the predictive factors for irAEs, but there are no reports focusing only on ICI plus platinum agents. The present study aimed to identify the risk factors for irAEs due to ICI combined with platinum-based induction immunochemotherapy in NSCLC patients, focusing only on the period of combined therapy and excluding the period of ICI maintenance therapy. METHODS: This retrospective study included 315 NSCLC patients who started ICI combined with platinum-based chemotherapy treatment at 14 hospitals between December 2018 and March 2021. A logistic regression analysis was used to explore the predictive factors. RESULTS: Fifty patients (15.9%) experienced irAEs. A multivariate analysis revealed that squamous cell carcinoma (P = 0.021; odds ratio [OR]: 2.30; 95% confidence interval [Cl]: 1.14-4.65), anti-programmed death 1 antibody (anti-PD-1) plus anti-cytotoxic T-lymphocyte antigen-4 antibody (anti-CTLA-4) regimens (P < 0.01; OR: 22.10; 95% Cl: 5.60-87.20), and neutrophil-to-lymphocyte rate (NLR) < 3 (P < 0.01; OR: 2.91; 95% Cl: 1.35-6.27) were independent predictive factors for irAEs occurrence. CONCLUSION: Squamous cell carcinoma, anti-PD-1 plus anti-CTLA-4 regimens, and NLR < 3 may be predictive factors for the occurrence of irAEs due to induction immunochemotherapy in patients with NSCLC. By focusing on the potential risk of irAEs in patients with these factors, irAEs can be appropriately managed from an early stage.

Total synthesis of (-)-domoic acid, a potent ionotropic glutamate receptor agonist and the key compound in oceanic harmful algal blooms.

The stereo-controlled total synthesis of (-)-domoic acid is described. The critical construction of the C1'-C2' Z-configuration was accomplished by taking advantage of an unsaturated lactam structure. The side chain fragment was introduced in the final stages of synthesis through a modified Julia-Kocienski reaction, aiming for its efficient derivatization.

Comparison of accuracy between augmented reality/mixed reality techniques and conventional techniques for epidural anesthesia using a practice phantom model kit.

BACKGROUND: This study used an epidural anesthesia practice kit (model) to evaluate the accuracy of epidural anesthesia using standard techniques (blind) and augmented/mixed reality technology and whether visualization using augmented/mixed reality technology would facilitate epidural anesthesia. METHODS: This study was conducted at the Yamagata University Hospital (Yamagata, Japan) between February and June 2022. Thirty medical students with no experience in epidural anesthesia were randomly divided into augmented reality (-), augmented reality (+), and semi-augmented reality groups, with 10 students in each group. Epidural anesthesia was performed using the paramedian approach with an epidural anesthesia practice kit. The augmented reality (-) group performed epidural anesthesia without HoloLens2Ⓡ and the augmented reality (+) group with HoloLens2Ⓡ. The semi-augmented reality group performed epidural anesthesia without HoloLens2Ⓡ after 30 s of image construction of the spine using HoloLens2Ⓡ. The epidural space puncture point distance between the ideal insertion needle and participant's insertion needle was compared. RESULTS: Four medical students in the augmented reality (-), zero in the augmented reality (+), and one in the semi-augmented reality groups failed to insert the needle into the epidural space. The epidural space puncture point distance for the augmented reality (-), augmented reality (+), and semi-augmented reality groups were 8.7 (5.7-14.3) mm, 3.5 (1.8-8.0) mm (P = 0.017), and 4.9 (3.2-5.9) mm (P = 0.027), respectively; a significant difference was observed between the two groups. CONCLUSIONS: Augmented/mixed reality technology has the potential to contribute significantly to the improvement of epidural anesthesia techniques.

[A Case of Transcatheter Arterial Chemoembolization and Surgical Resection of Left 7th Rib Metastasis after Surgery for Hepatocellular Carcinoma].

The patient was an 81-year-old man. After a liver posterior segmentectomy for hepatocellular carcinoma, a painful bulge was observed in the left anterior thoracic region during a routine outpatient visit. Elevated tumor markers and contrast- enhanced CT scan revealed a mass with contrast effect in the left 7th rib. Ultrasound-guided biopsy revealed hepatocellular carcinoma metastatic to the left 7th rib. There were no other obvious metastases, and the diagnosis of a single bone metastasis was made. The patient did not request chemotherapy and underwent transcatheter arterial chemoembolization 4 times. The patient did not show any improvement in tumor markers or shrinkage of the tumor, and his quality of life was deteriorated due to increased pain. The patient underwent left chest wall tumor resection and chest wall reconstruction. Postoperative tumor markers were normalized and pain improved markedly. We report a case of postoperative recurrence- free survival for 2 years.

Detection of Colorectal Neoplasms Using Linked Color Imaging: A Prospective, Randomized, Tandem Colonoscopy Trial.

BACKGROUND AND AIMS: A higher adenoma detection rate (ADR) has been shown to be related to a lower incidence and mortality of colorectal cancer. We analyzed the efficacy of linked color imaging (LCI) by assessing the detection, miss, and visibility of various featured adenomas as compared with white light imaging (WLI). METHODS: This was a prospective, randomized, tandem trial. The participants were randomly assigned to 2 groups: first observation by LCI, then second observation by WLI (LCI group); or both observations by WLI (WLI group). Suspected neoplastic lesions were resected after magnifying image-enhanced endoscopy. The primary outcome was to compare the ADR during the first observation. Secondary outcomes included evaluation of adenoma miss rate (AMR) and visibility score. RESULTS: A total of 780 patients were randomized, 700 of whom were included in the final analysis. The ADR was 69.6% and 63.2% in the LCI and WLI groups, respectively, with no significant difference. However, LCI improved the average ADR in low-detectors compared with high-detectors (76.0% vs 55.1%; P < .001). Total AMR was 20.6% in the LCI group, which was significantly lower than that in the WLI group (31.1%) (P < .001). AMR in the LCI group was significantly lower, especially for diminutive adenomas (23.4% vs 35.1%; P < .001) and nonpolypoid lesions (25.6% vs 37.9%; P < .001) compared with the WLI group. CONCLUSION: Although both methods provided a similar ADR, LCI had a lower AMR than WLI. LCI could benefit endoscopists with lower ADR, an observation that warrants additional study. (UMIN Clinical Trials Registry, Number: UMIN000026359).

Endoscopic Ultrasound Elastography as a Novel Diagnostic Method for the Assessment of Hardness and Depth of Invasion in Colorectal Neoplasms.

INTRODUCTION: We aimed to compare the efficacy of endoscopic ultrasound elastography (EUS-EG) with that of magnifying chromoendoscopy (MCE) and endoscopic ultrasonography (EUS) for the diagnosis of the depth of invasion in colorectal neoplasms. This is an important clinical issue as the depth of invasion is associated with the risk of metastasis. METHODS: Consecutive patients with suspected superficial colorectal neoplasms, evaluated by MCE, EUS, and EUS-EG, for whom endoscopic submucosal dissection was considered, were enrolled in 2018 (derivation study) and in 2019-2020 (validation study). The primary clinical endpoint was the diagnostic yield differentiating intramucosal and shallow submucosal neoplasms from deep submucosal (dSM) and advanced colorectal cancers. In addition, inter- and intra-observer agreements of the elastic score of colorectal neoplasm (ES-CRN) were evaluated by 2 expert and 2 non-expert endoscopists. RESULTS: Thirty-one (33 lesions) and 50 (55 lesions) patients were enrolled in the derivation and validation studies, respectively. Sensitivity, specificity, positive, and negative predictive values, and accuracy of assessment of the depth of submucosal or deeper invasion in the derivation and validation groups were as follows: EUS-EG, 100/88.2/86.7/100/93.3% and 77.8/86.1/73.7/88.6/83.3%; MCE, 66.7/94.4/90.9/77.3/81.8% and 84.2/91.4/84.2/91.4/88.9%; and EUS, 93.3/77.8/77.8/93.3/84.8% and 89.5/65.7/58.6/92.0/74.1%, respectively. For the 2 expert endoscopists, interobserver agreement for the ES-CRN (first and second assessments) in the derivation group was 0.84 and 0.78, respectively; these values were 0.73 and 0.49, respectively, for the 2 non-expert endoscopists. DISCUSSION/CONCLUSION: All 3 modalities presented similar diagnostic yield. Inter- and intra-observer agreements of the ES-CRN were substantial, even for non-expert endoscopists. Therefore, EUS-EG may be a useful modality in determining the depth of invasion in colorectal neoplasms.

The effect of perception of seat width on back-to-sit task.

[Purpose] The movement trajectory in daily motion is strongly associated with information regarding the properties of the environment. In the case of the back-to-sit task, it may vary according to chair property. The purpose of this study was to investigate whether trajectory formation in back-to-sit tasks by healthy adults depends on seat width information. [Participants and Methods] Ten healthy young males performed a back-to-sit task in 5 seat width conditions (80%, 90%, 100%, 110%, and 120% of each participant's buttock breadth). The motion analysis system and force plates were set at a sampling frequency of 250 Hz. The spatial and temporal variables were calculated to examine the effect of seat width. A questionnaire was also administered to examine whether the participants were aware of each seat width in comparison with their own buttock breadth as narrow or large. [Results] The questionnaire results showed that many participants were aware but some were unaware of the relative comparison of their size to the seat width. Nevertheless, the spatial and temporal variables were invariant under the different seat width conditions. [Conclusion] In healthy adults, the trajectory formation in back-to-sit tasks is not dependent on the perception of seat width information under their variability as per daily situations.

Computer-aided diagnosis for characterization of colorectal lesions: comprehensive software that includes differentiation of serrated lesions.

BACKGROUND AND AIMS: Endoscopy guidelines recommend adhering to policies such as resect and discard only if the optical biopsy is accurate. However, accuracy in predicting histology can vary greatly. Computer-aided diagnosis (CAD) for characterization of colorectal lesions may help with this issue. In this study, CAD software developed at the University of Adelaide (Australia) that includes serrated polyp differentiation was validated with Japanese images on narrow-band imaging (NBI) and blue-laser imaging (BLI). METHODS: CAD software developed using machine learning and densely connected convolutional neural networks was modeled with NBI colorectal lesion images (Olympus 190 series - Australia) and validated for NBI (Olympus 290 series) and BLI (Fujifilm 700 series) with Japanese datasets. All images were correlated with histology according to the modified Sano classification. The CAD software was trained with Australian NBI images and tested with separate sets of images from Australia (NBI) and Japan (NBI and BLI). RESULTS: An Australian dataset of 1235 polyp images was used as training, testing, and internal validation sets. A Japanese dataset of 20 polyp images on NBI and 49 polyp images on BLI was used as external validation sets. The CAD software had a mean area under the curve (AUC) of 94.3% for the internal set and 84.5% and 90.3% for the external sets (NBI and BLI, respectively). CONCLUSIONS: The CAD achieved AUCs comparable with experts and similar results with NBI and BLI. Accurate CAD prediction was achievable, even when the predicted endoscopy imaging technology was not part of the training set.

A simple method using anesthetics to test effects of sleep-inducing substances in mice.

We investigated the effects of sleep-inducing agents with different mechanisms of action on the loss of the righting reflex induced by isoflurane or a mixture of medetomidine, midazolam, and butorphanol (MMB), followed by atipamezole reversal. Chlorpromazine and brotizolam delayed recovery from both types of anesthesia, whereas the melatonin receptor agonist ramelteon had no effect. The orexin receptor antagonist suvorexant delayed recovery from anesthesia only in the case of MMB, while the sleep-promoting supplement glycine only delayed recovery in the case of isoflurane. These results suggest that the simple comparison method is applicable for testing substances expected to exert sleep-inducing effects.

An International Study on the Diagnostic Accuracy of the Japan Narrow-Band Imaging Expert Team Classification for Colorectal Polyps Observed with Blue Laser Imaging.

BACKGROUND: The Japan narrow-band imaging Expert Team (JNET) classification of colorectal polyps based on magnifying endoscopy is used in Japan, but not worldwide. The objective of this study was to clarify differences of diagnostic accuracy between JNET users in Japan and non-JNET users in other countries. METHODS: A total of 185 colorectal tumors were assessed. Six endoscopists (3 each from Japan and Taiwan) participated in the study. The Japanese endoscopists normally used the JNET classification and the Taiwanese endoscopists normally used the narrow-band imaging International Colorectal Endoscopic classification for diagnosis of colorectal tumors. After receiving a lecture on the JNET classification, they all observed one blue laser imaging magnified image per lesion and performed diagnosis based on the JNET classification. RESULTS: Diagnostic ability was equivalent for Type 1, Type 2A, and Type 2B. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value of Type 3 for deep submucosal invasive carcinoma was, respectively, 44.4, 98.3, 57.1, and 97.2% in Group J and 70.0, 94.7, 40.4, and 98.4% in Group T. The PPV for diagnosis of Type 3 with a high confidence was significantly higher in Group J than in Group T (81.8% [55.4-94.6] vs. 44.4% [33.6-50.9], p < 0.05). CONCLUSIONS: The PPV for Type 3 differed between the 2 groups, suggesting the need to become familiar with differentiation between Type 2B and Type 3.

Motor strategy for rapid gait initiation under conditions of limited center of pressure control.

[Purpose] The general motor strategy for gait initiation is achieved by the difference between the center of gravity and center of pressure; it be as bigger under speed optimization. This study aimed to investigate the motor pattern in rapid gait initiation under conditions of limited backward displacement of center of pressure. [Participants and Methods] The participants were 30 healthy young males (mean age, 19.7 ± 1.0 years). They performed a gait initiation task at three center of pressure start positions (anterior, middle, and posterior) and two speed conditions (normal and rapid). The gait initiation motion was measured using a video camera and motor pattern in the images was classified. The center of pressure position was continuously monitored using a pressure distribution measurement system. [Results] Forward tilt pattern was the most common under no limited center of pressure control and normal speed. The backward tilt pattern was the most preferred in the posterior position under limited center of pressure control and rapid speed. Displacement of the center of pressure showed a significant decline when the center of pressure start position was displaced backward. [Conclusion] The backward tilt pattern is the most effective motor strategy to increase the forward speed of the center of gravity.

Motor coordination during body rotation while standing in healthy participants.

[Purpose] To describe the nature of multi-joint motor coordination during body rotation while in the standing position. [Participants and Methods] The participants were 22 healthy adults with no visual problems or history of diseases that could compromise their ability to execute body rotation. The position facing forward in an upright standing position was defined as 0°, and targets were placed at the following five points on concentric circles: 30°, 60°, 90°, 120°, and 150°. The participants always turned to the right. A three-dimensional motion analyzer consisting of six infrared cameras was used to measure the spatial coordinates of the infrared reflective markers. [Results] A main effect was found for all body segments. For all the target angles, the start of movement was approximately equal, and the angular change of the craniocervical joint was the largest. A nonlinear relationship was observed between the craniocervical and thoracolumbar joints for all target angles. However, a linear relationship was found between the thoracolumbar and pelvic joints. [Conclusion] The results of this study demonstrate that various regions such as the craniocervical and thoracolumbar junctions and the pelvis coordinate during such move to achieve optimal locomotive patterns.

Frequency analysis of the center of pressure in tandem stance in community-dwelling elderly.

[Purpose] The present study aimed to clarify the effects of balance control on the pronation and supination movements of the talocrural joint in community-dwelling elderly women by conducting a frequency analysis of the center of pressure during tandem stance. [Subjects and Methods] The study participants were 18 subjects who maintained tandem stance for 20 s and 11 who had difficulty maintaining tandem stance for 20 s. The frequency-power spectra were computed and classified into three frequency bands. Each power spectral value was divided by the sum of the power spectral values to obtain the %power. [Results] Significant differences in high-frequency band %power value for the center of pressure in both the mediolateral and anteroposterior components were evident between the groups. [Conclusion] A markedly significant difference was observed, particularly in high frequency band %power, depending on balance control. The present findings indicated that elderly participants with diminished balance control had difficulty with rapid adjustment centered on the ankles, suggesting that rapid joint movement involving interlimb coordination centered on the ankles is required to maintain tandem stance.

The role of interaction torque and muscle torque in the control of downward squatting.

[Purpose] The purposes of this study were first to analyze the multijoint dynamics of downward squatting, and to examine the contribution of interaction torque and muscle torque to net torque, and second, to examine mechanisms of movement control. [Subjects] The subjects were 31 healthy men with a mean age of 21.0 ± 1.2 years (range, 19-24 years). [Methods] Squatting tasks with the trunk in two positions, an erect and anterior tilt position, were performed by the subjects. Net, interaction, muscle, and gravity torque were calculated according to the Lagrange equation using 3D tracking data. [Results] The contribution ratio of interaction torque to net torque was approximately 90%, irrespective of the joint and task. In contrast, muscle torque showed complicated behavior to compensate for gravity torque. A combined muscle and gravity torque profile showed flexion or dorsiflexion immediately after the initiation of the movement, and it later changed to extension or plantar flexion. [Conclusion] The torque that contributes almost exclusively to the net torque was interaction torque. The combination of muscle and gravity torque at the knee joint and the hip joint is important for movement control, independent of the starting position.

Postural optimization during functional reach while kneeling and standing.

[Purpose] The purpose of the present study was to examine the validity of functional reach models by comparing actual values with estimated values. [Subjects and Methods] Twenty-eight volunteers were included in this study (male: 14, female: 14, age: 21 ± 1 years, height: 166.8 ± 9.0 cm, and body mass: 60.1 ± 8.5 kg). The maximum forward fingertip position and joint angles were measured using the original equipment. In addition, the maximum forward fingertip position, shoulder joint angle, and knee or ankle joint angle were estimated using the functional reach model. [Results] The correlation coefficients between actual data and estimated data for the maximum forward fingertip position, shoulder joint angle, and ankle joint angle while standing were 0.93, 0.83, and 0.73, respectively. The correlation coefficients between actual data and estimated data for the maximum forward fingertip position, shoulder joint angle, and knee joint angle while kneeling were 0.86, 0.81, and 0.72, respectively. [Conclusion] The validity of both functional reach models in estimating optimal posture was confirmed. Therefore, the functional reach model is useful for evaluation of postural control and optimal postural control exercises.