Quality of Postoperative Recovery in Total Intravenous Anesthesia between Remimazolam and Propofol for Intraoperative Neurophysiological Monitoring: A Prospective Double-Blind Randomized Controlled Trial.

This study compared the overall postoperative recovery of patients who underwent total intravenous anesthesia with remimazolam or propofol, using the Quality of Recovery-15 questionnaire (QoR-15). Seventy-two patients who underwent spine surgery with intraoperative neurophysiological monitoring (IONM) were randomly categorized into the remimazolam group (group R) or propofol group (group P). On the first postoperative day, the QoR-15 scores for groups P and R were 114 and 112, respectively, indicating no significant difference (p = 0.691). Similarly, group-time interaction effects on QoR-15 scores were not significantly different. In the post-anesthesia care unit, the pain intensity at rest was notably higher in group P than in group R (3.0 [0.0] vs. 2.8 [0.5], respectively, p = 0.009). Although the intraoperative consumption of remifentanil was higher in group R (1452.4 µg vs. 2066.8 µg, respectively, p < 0.001), the intraoperative use of vasopressors was lower in group R (1705.6 µg vs. 286.1 µg, respectively, p < 0.001) compared to group P. Group R exhibited significantly lower variability in mean blood pressure over time compared to group P. Remimazolam was viewed as a promising intravenous agent for general anesthesia, showing potential to replace propofol in spine surgery with IONM, considering both recovery quality and intraoperative hemodynamic stability.

Comparison of Remimazolam versus Sevoflurane on the Postoperative Quality of Recovery in Cervical Spine Surgery: A Prospective Randomized Controlled Double-Blind Trial.

Purpose: Remimazolam is a newly developed ultra-short-acting benzodiazepine. We compared overall functional recovery, including the postoperative Quality of Recovery-15 (QoR-15) questionnaire scores, between balanced inhalational anesthesia using sevoflurane and total intravenous anesthesia (TIVA) with remimazolam in patients undergoing anterior cervical discectomy and fusion (ACDF). Patients and Methods: Seventy-two patients were randomized to the remimazolam (group R) or sevoflurane (group S) group. The primary outcome was the total QoR-15 score on postoperative day (POD) 1. We also assessed the total QoR-15 score on POD2, sub-scores of the QoR-15, perioperative parameters, and postoperative recovery profiles. Group-time interaction effects on the QoR-15 and its sub-scores were analyzed using a linear mixed model. Results: The total QoR-15 score on POD1 (120.2 in group R vs 114.3 in group S, P=0.189) was not statistically different between the groups. There were no significant group-time interaction effects on total QoR-15 scores. Instead, patients in group R showed significantly better sub-scores in psychological and postoperative nausea and vomiting (PONV) items on POD1, as well as a lower degree of PONV, than those in group S. Among the five dimensions of the QoR-15, a significant group-time interaction effect was observed for psychological support. Group R showed significantly less changeability in blood pressure and heart rate with a lower dose of intraoperatively administered vasopressor than group S. Conclusion: Considering QoR-15, including PONV reduction, and intraoperative hemodynamic stability, remimazolam can be used as the novel and safe anesthetic agent for maintaining general anesthesia instead of sevoflurane in patients undergoing ACDF.

Comparative Analysis of the Performance of Electroencephalogram Parameters for Monitoring the Depth of Sedation During Remimazolam Target-Controlled Infusion.

BACKGROUND: The changes in hypnotic indicators in remimazolam sedation remain unclear. We investigated the correlation of the electroencephalogram (EEG) parameters with the effect-site remimazolam concentration and the depth of sedation in patients receiving a target-controlled infusion of remimazolam. METHODS: This prospective observational study enrolled 35 patients (32 analyzed) who underwent lower extremity varicose vein surgery or lower extremity orthopedic surgery under spinal anesthesia. We administered remimazolam by target-controlled infusion using the pharmacokinetic model introduced by Schüttler et al. The EEG data were continuously recorded, including the bispectral index (BIS), patient state index (PSI), spectral edge frequency (SEF), and raw EEG signals. The relative beta ratio (RBR), defined as log (spectral power [30-47 Hz]/spectral power [11-20 Hz]), was obtained by analyzing raw EEG. The level of sedation corresponding to each effect-site remimazolam concentration was assessed using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S). The prediction probability (Pk) and Spearman's correlation coefficients (R) were calculated between effect-site remimazolam concentration, MOAA/S, and EEG parameters. RESULTS: BIS and PSI showed significantly higher Pk for effect-site remimazolam concentration (Pk = 0.76 [0.72-0.79], P < .001 for BIS; Pk = 0.76 [0.73-0.79], P < .001 for PSI) compared to RBR (Pk = 0.71 [0.68-0.74], P < .001) and SEF (Pk = 0.58 [0.53-0.63], P = .002). BIS, PSI, and RBR showed significantly higher correlation coefficients for effect-site remimazolam concentration (R = -0.70 [-0.78 to -0.63], P < .001 for BIS; R = -0.72 [-0.79 to -0.66], P < .001 for PSI; R = -0.61 [-0.69 to -0.54], P < .001 for RBR) compared to SEF (R = -0.22 [-0.36 to -0.08], P = .002). BIS and PSI also had significantly higher Pk and correlation coefficients for MOAA/S (Pk = 0.81 [0.79-0.83], P < .001; R = 0.84 [0.81-0.88], P < .001 for BIS) (Pk = 0.80 [0.78-0.83], P < .001; R = 0.82 [0.78-0.87], P < .001 for PSI) compared to RBR (Pk = 0.74 [0.72-0.77], P < .001; R = 0.72 [0.65-0.78], P < .001) and SEF (Pk = 0.55 [0.50-0.59], P = .041; R = 0.13 [-0.01 to 0.27], P = .067). CONCLUSIONS: BIS, PSI, and RBR showed an acceptable correlation with the effect-site remimazolam concentration and depth of sedation in this study, suggesting that these EEG-derived parameters are potentially reliable hypnotic indicators during remimazolam sedation. BIS and PSI showed superior performance as hypnotic indicators to RBR and SEF in patients receiving target-controlled infusion of remimazolam.

Prognostic role of body composition in peritoneal carcinomatosis patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Bioelectric impedance analysis (BIA)-measured body composition and nutritional status have been used as prognostic indicators in various cancer cohorts. This study investigated whether BIA could provide information on prognosis in peritoneal carcinomatosis patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: We retrospectively analyzed the data of 99 patients with preoperative BIA data among those who underwent CRS and HIPEC. The association between BIA-derived parameters and intraoperative peritoneal cancer index (PCI) score was assessed. Predictive analysis for the occurrence of postoperative morbidities including major complications (Clavien-Dindo classification 3-4) and re-admission within 30 days after surgery as well as 1 year mortality was also performed. RESULTS: BIA-derived mineral (r = 0.224, p = 0.027), fat (r = - 0.202, p = 0.048), and total body water (TBW)/fat-free mass (FFM) (r = - 0.280, p = 0.005) showed significant associations with intraoperative PCI score. Lower TBW/FFM was an independent predictor of major postoperative complications (OR 0.047, 95% CI 0.003-0.749, p = 0.031) and re-admission (OR 0.094, 95% CI 0.014-0.657, p = 0.017) within 30 days after surgery. Higher fat mass was also independently associated with a higher risk of major postoperative complications (OR 1.120, 95% CI 1.006-1.248, p = 0.039) and re-admission (OR 1.123, 95% CI 1.024-1.230, p = 0.013). Intraoperative PCI score > 20 (OR 4.489, 95% CI 1.191-16.917, p = 0.027) and re-admission within 30 days after surgery (OR 5.269, 95% CI 1.288-21.547, p = 0.021) independently predicted postoperative 1-year mortality. CONCLUSIONS: We demonstrate that preoperative BIA-derived TBW/FFM and fat mass were significantly correlated with metastatic extent, assessed by PCI score, in patients with peritoneal carcinomatosis. In addition, BIA-derived TBW/FFM and fat mass showed independent predictability for postoperative 30-day major complications and re-admission in patients undergoing CRS and HIPEC. Our findings suggest that assessment of BIA may improve discrete risk stratification in patients who are planned to receive CRS and HIPEC.

Comparison of injectate spread and nerve coverage between single-injection intertransverse process block and paravertebral block at the T2 level: a cadaveric study.

BACKGROUND: We compared the spread of an injectate into the thoracic sympathetic chain resulting from a single-injection intertransverse process (ITP) block with that of a single-injection PV block at the T2 level. METHODS: Sixteen soft-embalmed cadavers were used. The right hemithorax was randomly allocated to receive either an ultrasound-guided single-injection ITP block or ultrasound-guided single-injection PV block at the T2 vertebral level, with the opposite block administered to the other side. Approximately 10 mL of latex dye solution was injected into each hemithorax using a random allocation technique. The presence of dye at the nerve root in the sympathetic chain and intercostal nerves at the injection and additional levels was examined by dissection. RESULTS: The injectate spread into the T2 sympathetic ganglion on both ITP (11/16, 68.8%) and PV (16/16, 100%) blocks. The ITP block demonstrated greater uniformity of dye staining in both the dorsal rami and dorsal root ganglion, which contrasts with the less consistent staining outcomes of the PV block in these regions. CONCLUSIONS: At the T2 level, we observed a lower efficacy of the ITP block for analgesic coverage of the sympathetic nerve. This suggested a potential preference by clinicians for the application of the T2 PV block over the ITP block, specifically for the management of sympathetically maintained pain in the upper extremities. In addition, our findings may hint at the potential advantages of the ITP block in specific clinical contexts where targeted nerve involvement, such as the medial branch block or dorsal root ganglion block, is sought.

Smoking behavior change and the risk of pneumonia hospitalization among smokers with diabetes mellitus.

Smoking patients with diabetes mellitus (DM) are at greater risk of developing pneumonia. How smoking behavior changes affect the risk of pneumonia hospitalization, however, remains unclear. Therefore, we investigated the association between smoking behavior change and the risk of pneumonia hospitalization in patients with DM. From January 1, 2009 and December 31, 2018, we investigated the association between smoking behavior change and the risk of pneumonia hospitalization in patients with DM. A total of 332,798 adult patients with DM from the Korean National Health Insurance System database who underwent health screening examination between 2009 and 2012, and were smokers at the first health examination were included. During a mean follow-up of 4.89 years, 14,598 (4.39%) incident pneumonia hospitalization cases were identified. Reducers had a slightly increased risk of pneumonia hospitalization (aHR 1.06, 95% CI 1.01-1.10) compared to sustainers. Quitters did not have a significant association with incidence of pneumonia hospitalization. However, increasers had 13% higher risk of pneumonia hospitalization (aHR 1.13, 95% CI 1.07-1.18), regardless of whether initial smoking was light, moderate, or heavy. Our study showed that an increase in smoking intensity was associated with an increased risk of pneumonia hospitalization in people with DM. However, a protective effect of smoking reduction or cessation on pneumonia risk was not demonstrated.

Efficient Labeling of Vesicles with Lipophilic Fluorescent Dyes via the Salt-Change Method.

Fluorescent labeling allows for imaging and tracking of vesicles down to single-particle level. Among several options to introduce fluorescence, staining of lipid membranes with lipophilic dyes provides a straightforward approach without interfering with vesicle content. However, incorporating lipophilic molecules into vesicle membranes in an aqueous solution is generally not efficient because of their low water solubility. Here, we describe a simple, fast (<30 min), and highly effective procedure for fluorescent labeling of vesicles including natural extracellular vesicles. By adjusting the ionic strength of the staining buffer with NaCl, the aggregation status of DiI, a representative lipophilic tracer, can be controlled reversibly. Using cell-derived vesicles as a model system, we show that dispersion of DiI under low-salt condition improved its incorporation into vesicles by a factor of 290. In addition, increasing NaCl concentration after labeling induced free dye molecules to form aggregates, which can be filtered and thus effectively removed without ultracentrifugation. We consistently observed 6- to 85-fold increases in the labeled vesicle count across different types of dyes and vesicles. The method is expected to reduce the concern about off-target labeling resulting from the use of high concentrations of dyes.

Anatomical and Radiological Assessments of Injectate Spread Stratified by the Volume of the Pericapsular Nerve Group Block.

BACKGROUND: The pericapsular nerve group (PENG) block was recently suggested as a regional technique for managing acute pain after hip surgery. However, few anatomical studies have confirmed the spread of injectate during the PENG block. This cadaver study aimed to analyze injectate spread to the target nerves during single-injection ultrasound-guided PENG block. METHODS: Ultrasound-guided PENG block with 3 different injectate volumes (10, 20, or 30 mL) was performed in 18 cadavers. Injectate spread by the volume was first evaluated on computed tomography, followed by cadaver dissection. The spread of the dye over the pelvis and lower limb was evaluated. RESULTS: The articular branches of the femoral nerve were stained nearly sufficiently with 20- and 30-mL specimens. The femoral nerve itself was stained simultaneously in six of 12 (50%) 20-mL specimens and 12 of 12 (100%) 30-mL specimens. The accessory obturator nerve was observed only in three (9%) of 36 specimens. The articular branches of the obturator nerve were rarely affected, regardless of injectate volume (1/12, 10 mL specimens; 2/12, 20 mL specimens; 1/12, 30 mL specimens; P > .999). Rather, the obturator nerve was affected. However, the obturator nerve was not stained consistently even with 30 mL of injectate (50%). CONCLUSIONS: After combining the dissection and radiological findings, the single-injection ultrasound-guided PENG blocks with volumes of 10, 20, and 30 mL do not support motor sparing or selective anterior hip capsule innervation in a clinical setting. If early rehabilitation is needed, high-volume PENG block might not be the ideal option, and persisting pain after PENG block might be attributed in part to the lack of obturator nerve articular branches blockade.

Practical role of preoperative echocardiography in low-risk non-cardiac surgery.

Background: Due to increased needs to reduce non-fatal as well as fatal cardiac events, preoperative echocardiography remains part of routine clinical practice in many hospitals. Data on the role of preoperative echocardiography in low-risk non-cardiac surgery (NCS) other than ambulatory surgeries do not exist. We aimed to investigate the role of preoperative echocardiography in predicting postoperative adverse cardiovascular events (CVEs) in asymptomatic patients undergoing low-risk NCS. Methods: The study population was derived from a retrospective cohort of 1,264 patients who underwent elective low-risk surgery at three tertiary hospitals from June 1, 2021, to June 30, 2021. Breast, distal bone, thyroid, and transurethral surgeries were included. Preoperative examination data including electrocardiography, chest radiography, and echocardiography were collected. The primary outcome was a composite of postoperative adverse CVEs including all-cause death, myocardial infarction, cerebrovascular events, newly diagnosed or acutely decompensated heart failure (HF), lethal arrhythmia such as sustained ventricular tachycardia/fibrillation, and new-onset atrial fibrillation within 30 days after the index surgery. Results: Preoperative echocardiography was performed in 503 patients (39.8%), most frequently in patients with breast surgery (73.5%), followed by transurethral (37.7%), distal bone (21.6%), and thyroid surgeries (11.9%). Abnormal findings were observed in 5.0% of patients with preoperative echocardiography. Postoperative adverse CVEs occurred in 10 (0.79%) patients. Although a history of previous HF was an independent predictor of postoperative CVE occurrence (adjusted odds ratio, aOR: 17.98; 95% confidence interval, CI: 1.21-266.71, P = 0.036), preoperative echocardiography did not significantly predict CVE in multivariate analysis (P = 0.097). However, in patients who underwent preoperative echocardiography, the presence of abnormal echocardiographic findings was independently associated with development of CVE after NCS (aOR: 23.93; 95% CI: 1.2.28-250.76, P = 0.008). In particular, the presence of wall motion abnormality was a strong predictor of postoperative adverse CVE. Conclusion: In real-world clinical practice, preoperative echocardiography was performed in substantial number of patients with potential cardiac risk even in low-risk NCS, and abnormal findings were independently associated with postoperative CVE. Future studies should identify patients undergoing low-risk NCS for whom preoperative echocardiography would be helpful to predict adverse CVE.

Association between preoperative frontal electroencephalogram alpha asymmetry and postoperative quality of recovery: an observational study.

BACKGROUND: Left-sided frontal alpha asymmetry on electroencephalograms, which indicates decreased relative left-hemispheric activity, has been associated with depression, anxiety, and stress responsivity. We aimed to evaluate the association between perioperative measures of frontal alpha asymmetry and quality of recovery (QoR) after surgery. METHODS: We enrolled 110 female patients undergoing thyroidectomy and recorded perioperative electroencephalograms. The power of the prefrontal alpha band (8-13 Hz) was measured in the Fp1 and Fp2 leads. Left-sided frontal alpha asymmetry was defined as a higher alpha band power in Fp1 than in Fp2 and vice versa. QoR was assessed using the QoR-15 score on the day before surgery and postoperative days 1 and 2. The primary study endpoint was a difference in postoperative global QoR-15 score between preoperative left-sided and right-sided alpha asymmetry groups. The predictability of frontal alpha asymmetry for poor QoR-15 score was also evaluated. RESULTS: The global QoR-15 score showed a significant group-by-time interaction, and post-hoc analysis revealed significantly lower scores on postoperative days 1 (P=0.006) and 2 (P<0.001) in the left-sided frontal alpha asymmetry group. In the multivariate logistic regression analysis, preoperative left-sided frontal alpha asymmetry was associated with a 3.3-fold increased risk of the lowest tertile for the postoperative day 1 QoR-15 score (95% CI: 1.31-8.24; P=0.011). CONCLUSIONS: Preoperative left-sided frontal alpha asymmetry was independently associated with a lower postoperative QoR-15 score in female patients undergoing thyroidectomy, highlighting the potential role of preoperative frontal electroencephalography in predicting patient-centred outcomes after surgery. CLINICAL TRIAL REGISTRATION: KCT0006586 (http://cris.nih.go.kr/).

PRE-OPerative ECHOcardiograhy for prevention of cardiovascular events after non-cardiac surgery in intermediate- and high-risk patients: protocol for a low-interventional, mixed-cohort prospective study design (PREOP-ECHO).

BACKGROUND: Cardiac evaluation using transthoracic echocardiography before noncardiac surgery is common in real-world practice. However, evidence supporting preoperative echocardiography is lacking. This study aims to evaluate the additional benefit of preoperative echocardiography in predicting postoperative cardiovascular events (CVE) in noncardiac surgery. METHODS: This study is designed as a multicenter, prospective study to assess the utility of preoperative echocardiography in patients undergoing intermediate- or high-risk noncardiac surgery. This trial comprises two studies: (1) a randomized controlled trial (RCT) for patients undergoing intermediate-risk surgery with fewer than three clinical risk factors from the revised cardiac risk index (intermediate-risk group) and (2) a prospective cohort study for patients undergoing intermediate-risk surgery with three or more clinical risk factors, or who undergo high-risk surgery regardless of the number of clinical risk factors (high-risk group). We hypothesize that the use of preoperative echocardiography will reduce postoperative CVEs in patients undergoing intermediate- to high-risk surgery through discovery of and further intervention for unexpected cardiac abnormalities before elective surgery. A total of 2330 and 2184 patients will be enrolled in the two studies. The primary endpoint is a composite of all-cause death; aborted sudden cardiac arrest; type I acute myocardial infarction; clinically diagnosed unstable angina; stress-induced cardiomyopathy; lethal arrhythmia, such as sustained ventricular tachycardia or ventricular fibrillation; and/or newly diagnosed or acutely decompensated heart failure within 30 days after surgery. DISCUSSION: This study will be the first large-scale prospective study examining the benefit of preoperative echocardiography in predicting postoperative CVE. The PREOP-ECHO trial will help doctors identify patients at risk of postoperative CVE using echocardiography and thereby reduce postoperative CVEs. TRIAL REGISTRATION: The Clinical Research Information Service KCT0006279 for RCT and KCT0006280 for prospective cohort study. Registered on June 21, 2021.

Comparison of remimazolam-based and propofol-based total intravenous anesthesia on postoperative quality of recovery: A randomized non-inferiority trial.

STUDY OBJECTIVE: The quality of recovery (QoR) of remimazolam-based and propofol-based total intravenous anesthesia was compared as measured by QoR-15 scores. DESIGN: A prospective, double-blind, randomized controlled, non-inferiority trial. SETTING: An operating room, a post-anesthesia care unit (PACU), and a hospital ward. PATIENTS: Female patients (n = 140; 20-65 years) scheduled for open thyroidectomy were enrolled and randomly assigned to the remimazolam or propofol group. INTERVENTIONS: The remimazolam group received continuous remimazolam infusions and effect-site target-controlled remifentanil infusions. The propofol group received effect-site target-controlled infusions of propofol and remifentanil. MEASUREMENTS: The primary outcome was QoR-15 on postoperative day 1 (POD1). The mean difference between the groups was compared against a non-inferiority margin of -8. Secondary outcomes were QoR-15 on POD2, hemodynamic data, time to lose and recover consciousness, sedation score upon PACU admission, pain, and postoperative nausea and vomiting profiles at the PACU and ward. Group-time interaction effects in hemodynamic data and QoR-15 were analyzed using a linear mixed model. MAIN RESULTS: The total QoR-15 score on POD1 in the remimazolam group was non-inferior to that in the propofol group (mean [SD] 111.2 [18.8] vs. 109.1 [18.9]; mean difference [95% CI] 2.1 [-4.2, 8.5]; p = 0.002 for non-inferiority). The QoR-15 score on POD2 was comparable between the groups, and no group-time interaction was observed. At the end of anesthesia, after extubation, and upon arrival at the PACU, mean arterial pressure was significantly higher in the remimazolam group. Remimazolam group was more sedated at the time of admission to PACU. Pain intensity and the requirement for analgesics were lower in the remimazolam group than in the propofol group. CONCLUSIONS: Remimazolam-based total intravenous anesthesia provided a similar QoR to propofol. Remimazolam and propofol can be used interchangeably for general anesthesia in female patients undergoing thyroid surgery.

Dexmedetomidine attenuates subarachnoid hemorrhage-induced acute lung injury through regulating autophagy and TLR/NFκB signaling pathway.

BACKGROUND: Acute lung injury (ALI) is the most serious complication of subarachnoid hemorrhage (SAH). We investigated role of autophagy and inflammatory signaling pathways in lung damage and therapeutic effects of dexmedetomidine (DEX). METHODS: Fifty male Wistar rats were randomly divided into five groups: sham, SAH, SAH+ DEX5, SAH+DEX25, and SAH+DEX50. SAH was induced using endovascular perforation technique. All rats received mechanical ventilation for 60 minutes. At 2 and 24 h of SAH induction, SAH+DEX groups were treated with 5, 25, and 50 µg/kg of DEX, respectively. Histological ALI score and pulmonary edema were assessed after 48 h. Lung expression of LC3B, ATG3, p62, TLR4, TLR9, and NFκB was assessed using western blotting and quantitative PCR. Blood levels of IL-6, IL-1ß, IFN-γ, and TNFα were also assessed. RESULTS: SAH induced ALI and pulmonary edema, which were attenuated in SAH+DEX5 (P < 0.001 for both) and SAH+DEX25 groups (P = 0.001 and P < 0.001 for ALI and edema, respectively). Lung expressions of LC3B and ATG3 were upregulated in SAH group, which was attenuated in SAH+DEX5 and SAH+DEX25 groups. Lung expressions of TLR4, TLR9, and NFκB were increased in SAH group, which was attenuated in SAH+DEX5 group. Blood IL-6 level was increased in SAH group and attenuated in SAH+DEX5 and SAH+DEX25 groups. Blood IFN-γ level was lower in SAH group than in sham group, and it was increased in SAH+DEX25 group. CONCLUSIONS: Low-dose DEX treatment after SAH may protect against ALI by disrupting pathological brain-lung crosstalk and alleviating autophagy flux and TLR-dependent inflammatory pathways.

Effect of Previous Caudal Block to Predict Successful Outcome after Adhesiolysis using a Steerable Catheter in Lumbar Failed Back Surgery Syndrome: A Retrospective Study.

Adhesiolysis is minimally invasive and commonly used for pain associated with adhesion after lumbar spine surgery. Caudal epidural block may be used for radiating pain due to failed back surgery syndrome. We evaluated the predictive value of response to caudal block performed prior to adhesiolysis in failed back surgery syndrome. Between January 1, 2013 and June 30, 2020, 150 patients with failed back surgery syndrome were treated with adhesiolysis using a steerable catheter at the pain clinic of a tertiary hospital after failed conservative treatment (including caudal block). Patient demographics, pain duration, and lumbar magnetic resonance imaging findings were examined. Response to previous caudal block was determined as a binary result (yes or no). Patients were followed up 3 months after adhesiolysis. Successful outcome was defined as a ≥2-point reduction in the numeric rating scale scores for radicular pain 3 months after adhesiolysis, evident in 81/150 (46%) patients. Multivariable logistic regression analysis revealed that caudal block response was an independent predictor of successful adhesiolysis (odds ratio = 4.403; p = 0.015). Response to prior caudal block is a positive predictor of successful adhesiolysis.

Pharmacodynamic analysis of intravenous bolus remimazolam for loss of consciousness in patients undergoing general anaesthesia: a randomised, prospective, double-blind study.

BACKGROUND: Remimazolam is a new rapid offset benzodiazepine used for procedural sedation and general anaesthesia. This study evaluated the efficacy and safety of i.v. bolus remimazolam during induction of anaesthesia. METHODS: A total of 120 patients undergoing general anaesthesia were randomly allocated into six dose groups (n=20) of i.v. bolus remimazolam (0.02-0.27 mg kg-1). Loss of consciousness, respiratory depression, patient state index (PSI), and haemodynamic variables were evaluated during anaesthetic induction. Parametric time-to-event models were used to identify the 50% effective dose (ED50)/95% effective dose (ED95) associated with loss of consciousness and respiratory depression. Non-linear mixed-effect models analysed the PSI and haemodynamic changes after i.v. bolus remimazolam. RESULTS: Loss of consciousness and respiratory depression onset showed steep dose-responses with ED50/ED95 of 0.11/0.19 and 0.14/0.27 mg kg-1 and Hill coefficients of 5.3 and 4.6, respectively. Older age was significantly associated with lower ED50/ED95 for both endpoints. ED50/ED95 and the Hill coefficient of PSI decline were 0.12/0.68 mg kg-1 and 1.7, respectively. We propose optimal doses of 0.25-0.33, 0.19-0.25, and 0.14-0.19 mg kg-1 in patients aged <40, 60-80, and >80 yr, respectively, based on the ED95 estimates for the corresponding age groups. The maximum percentage reduction of MAP was 27.8% and the ED50/ED95 were 0.14/2.60 mg kg-1. The effect of remimazolam on heart rate was insignificant. CONCLUSIONS: The ED50/ED95s of i.v. bolus remimazolam were successfully estimated from the time to loss of consciousness and respiratory depression. No serious adverse events occurred within the range of tested doses. CLINICAL TRIAL REGISTRATION: NCT04901871.

Extracellular pyruvate kinase M2 promotes osteoclastogenesis and is associated with radiographic progression in early rheumatoid arthritis.

Extracellular PKM2 (exPKM2) levels have been reported to be increased in several cancers and inflammatory diseases, including rheumatoid arthritis (RA). This study aimed to investigate the association of circulating exPKM2 levels with radiographic progression in RA patients and the effect of exPKM2 on osteoclastogenesis. Plasma and synovial fluid exPKM2 levels were significantly elevated in RA patients. Plasma exPKM2 levels were correlated with RA disease activity and were an independent predictor for radiographic progression in RA patients with a disease duration of ≤ 12 months. CD14+ monocytes but not RA fibroblast-like synoviocytes secreted PKM2 upon stimulation with inflammatory mediators. Recombinant PKM2 (rPKM2) increased the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells and resorption pit in osteoclast precursors, dose-dependently, even in the absence of receptor activator of nuclear factor-kappa B ligand (RANKL). rPKM2 treatment upregulated the expression of dendrocyte-expressed seven transmembrane protein (DC-STAMP) and MMP-9 via the ERK pathway. Although rPKM2 did not directly bind to RAW264.7 cells, extracellular application of pyruvate, the end-product of PKM2, showed effects similar to those seen in rPKM2-induced osteoclastogenesis. These results suggest that exPKM2 is a potential regulator of RA-related joint damage and a novel biomarker for subsequent radiographic progression in patients with early-stage RA.

The Impact of Air Pollutants and Meteorological Factors on Chronic Obstructive Pulmonary Disease Exacerbations: A Nationwide Study.

Rationale: Chronic obstructive lung disease (COPD) is a chronic progressive disease. Although smoking is the most important risk factor, 30% of patients with COPD are never-smokers, and environmental agents are also influential. The effects of air pollutants and meteorological factors on COPD exacerbations have not been studied extensively. Objectives: We aimed to investigate the air pollutants and meteorological factors that impact the incidence of COPD exacerbations. Methods: We obtained clinical data of COPD exacerbation cases from The National Health Insurance Service and merged it with 24-hour average values of air pollutants and meteorological factors from national databases. Patients who reside in eight metropolitan cities, where observatory stations are densely located, were selected for analysis. Results: In 1,404,505 patients with COPD between 2013 and 2018, 15,282 COPD exacerbations leading to hospitalization or emergency room visits were identified. Among the various air pollutants and meteorological factors, particulate matter ⩽2.5 µm in aerodynamic diameter (PM2.5), particulate matter ⩽10 µm in aerodynamic diameter (PM10), NO2, SO2, CO, O3, average temperature, and diurnal temperature range (DTR) were associated with COPD exacerbations. Generalized additive mode model analysis with cubic splines showed an inverted U-shaped relationship with PM2.5, PM10, CO, NO2, SO2, O3, DTR, and humidity, whereas it displayed a U-shaped pattern with the average temperature. Distinct patterns were found from 2015-2016 to 2017-2018. Conclusions: PM2.5, PM10, CO, NO2, O3, SO2, average temperature, humidity, and DTR affected the incidence of COPD exacerbations in various patterns, up to 10 lag days.

Cavity formation and its predictors in noncavitary nodular bronchiectatic Mycobacterium avium complex pulmonary disease.

INTRODUCTION: The temporal dynamics of cavity formation in patients with the noncavitary nodular bronchiectatic (NC-NB) form of Mycobacterium avium complex pulmonary disease (MAC-PD) have not yet been well described. We aimed to investigate the development of new cavities in the NC-NB form of MAC-PD. METHODS: Of the patients diagnosed with NC-NB-type MAC-PD between 2002 and 2013 and followed-up until July 2018 at a tertiary referral center in South Korea, we identified 589 patients who underwent follow-up chest computed tomography at least once after the diagnosis and retrospectively analysed their medical records. RESULTS: The patients' mean age was 62.0 years, 64.7% were women. During the median follow-up of 3.8 years (interquartile range [IQR] 1.7-5.9), new cavity formation was noted in 51 (8.7%) patients. The median interval between the diagnosis of NC-NB MAC-PD and cavity formation was 3.7 years (IQR 1.8-5.4), with a constant occurrence over time. The Cox regression analysis showed that a history of pulmonary tuberculosis (adjusted hazard ratio [HR] 1.85; 95% confidence interval [CI] 1.06-3.23; P = 0.030) and M. intracellulare as the causative organism (adjusted HR 2.03; 95% CI 1.15-3.59; P = 0.014) were independently associated with new cavity formation. CONCLUSIONS: New cavity formation was noted in 8.7% of the patients with NC-NB MAC-PD in approximately 4 years after diagnosis, particular in those infected with M. intracellulare and those with a previous history of tuberculosis.