The Effect of Postoperative Single-Injection Adductor Canal Block in Total Knee Arthroplasty Under Spinal Anesthesia With Intraoperative Dexmedetomidine Infusion.

Background: Single-injection adductor canal block (SACB) is one of the multimodal pain managements in total knee arthroplasty. The effect of an intrathecal local anesthetic is prolonged with an intraoperative dexmedetomidine infusion. Currently, SACB's effect along with the prolonged spinal anesthesia effect by dexmedetomidine has not been studied elsewhere. Methods: Seventy-eight patients were randomized to either the SACB group (n = 39) or the control group (n = 39). Spinal anesthesia and continuous infusion of dexmedetomidine were performed intraoperatively. The SACB was performed using 15 mL of either 0.5% ropivacaine or normal saline in postanesthesia care unit postoperatively. Primary endpoint examined the average numerical rating scale (NRS) pain scores at 2, 6, 12, and 24 hours after SACB while resting or moving. The secondary outcomes were the morphine equivalent, postoperative nausea and vomiting score, quadriceps strength, and overall satisfaction score. Results: The SACB group showed a lower average NRS pain score until 24 hours than the control group (2.4 vs 3.3 resting, 3.4 vs 4.1 moving). Resting and moving NRS scores at 6 and 12 hours were significantly lower in the SACB group, whereas no difference was found at 2, 24, and 48 hours, regardless of movement. The satisfaction score was higher in the SACB group than in the control group (9 [7.3-10.0] vs 7 [5.3-8.8]), and morphine equivalent at 2 hours was lower in the SACB group (2 [1-3]) than in the control group (2.9 [1.6-4]). Conclusions: SACB provided an additional analgesic effect in patients undergoing total knee arthroplasty under spinal anesthesia with continuous dexmedetomidine intravenous infusion.

Relationship between preinduction electroencephalogram patterns and propofol sensitivity in adult patients.

PURPOSE: To determine the precise induction dose, an objective assessment of individual propofol sensitivity is necessary. This study aimed to investigate whether preinduction electroencephalogram (EEG) data are useful in determining the optimal propofol dose for the induction of general anesthesia in healthy adult patients. METHODS: Seventy healthy adult patients underwent total intravenous anesthesia (TIVA), and the effect-site target concentration of propofol was observed to measure each individual's propofol requirements for loss of responsiveness. We analyzed preinduction EEG data to assess its relationship with propofol requirements and conducted multiple regression analyses considering various patient-related factors. RESULTS: Patients with higher relative delta power (ρ = 0.47, p < 0.01) and higher absolute delta power (ρ = 0.34, p = 0.01) required a greater amount of propofol for anesthesia induction. In contrast, patients with higher relative beta power (ρ = -0.33, p < 0.01) required less propofol to achieve unresponsiveness. Multiple regression analysis revealed an independent association between relative delta power and propofol requirements. CONCLUSION: Preinduction EEG, particularly relative delta power, is associated with propofol requirements during the induction of general anesthesia. The utilization of preinduction EEG data may improve the precision of induction dose selection for individuals.

Cardioprotection via mitochondrial transplantation supports fatty acid metabolism in ischemia-reperfusion injured rat heart.

In addition to cellular damage, ischemia-reperfusion (IR) injury induces substantial damage to the mitochondria and endoplasmic reticulum. In this study, we sought to determine whether impaired mitochondrial function owing to IR could be restored by transplanting mitochondria into the heart under ex vivo IR states. Additionally, we aimed to provide preliminary results to inform therapeutic options for ischemic heart disease (IHD). Healthy mitochondria isolated from autologous gluteus maximus muscle were transplanted into the hearts of Sprague-Dawley rats damaged by IR using the Langendorff system, and the heart rate and oxygen consumption capacity of the mitochondria were measured to confirm whether heart function was restored. In addition, relative expression levels were measured to identify the genes related to IR injury. Mitochondrial oxygen consumption capacity was found to be lower in the IR group than in the group that underwent mitochondrial transplantation after IR injury (p < 0.05), and the control group showed a tendency toward increased oxygen consumption capacity compared with the IR group. Among the genes related to fatty acid metabolism, Cpt1b (p < 0.05) and Fads1 (p < 0.01) showed significant expression in the following order: IR group, IR + transplantation group, and control group. These results suggest that mitochondrial transplantation protects the heart from IR damage and may be feasible as a therapeutic option for IHD.

Physical Activity Intensity and Risk of Dementia.

INTRODUCTION: Regular participation in aerobic physical activity is associated with a reduced risk of dementia. It is currently unclear whether this association is due to the total volume or intensity of physical activity. METHODS: This prospective cohort study analyzed 386,486 adults from the UK Biobank who were free of dementia and self-reported >0 minutes of moderate-to-vigorous intensity physical activity (MVPA) at baseline (2007-2010). Participants were categorized as performing 0%, >0%-30%, or >30% of their total MVPA in vigorous activity (VPA). Cox proportional hazards regression models were used to examine the associations between categories of VPA and incident dementia while adjusting for sociodemographic and lifestyle factors including total MVPA. Analyses were performed in 2022. RESULTS: Over an average follow-up of 12.0 (1.7) years, there were 5,177 (1.3%) cases of dementia. Compared to the group reporting 0% VPA, the hazard ratios (95% confidence intervals) of dementia for the groups reporting >0%-30% and >30% VPA were 0.73 (0.68-0.78) and 0.81 (0.75-0.87), respectively, in the fully adjusted model. In a joint analysis, reporting some VPA was associated with a reduced risk of dementia regardless of meeting the aerobic physical activity guidelines (HR=0.78 [0.72-0.85]) or not (HR=0.76 [0.60-0.98]), while meeting the aerobic physical activity guidelines alone without VPA was not associated with incident dementia (HR=0.98 [0.90-1.07]), compared to the group that did not meet the guidelines and reported no VPA. CONCLUSIONS: These results suggest that engaging in VPA as part of MVPA is associated with a lower risk of dementia.

Preoperative frailty assessment with ultrasound in elderly patients scheduled for total knee arthroplasty.

BACKGROUND: Frailty, a decline in physical and cognitive reserve capacity, renders patients susceptible to various stressors and has been linked to adverse outcomes and increased healthcare utilization. This study aimed to determine whether ultrasound measurements of the rectus abdominis (RA) and biceps brachii (BB) could predict frailty in patients scheduled for total knee arthroplasty. METHODS: Frailty was assessed using the Clinical Frailty Scale in adults aged ≥60 years. Ultrasound measurements of the rectus abdominis, BB, and quadriceps femoris muscles, along with thigh circumference measurements, were obtained before surgery. The predictive ability of the unadjusted and BMI- and body surface area (BSA)-adjusted measurements were evaluated using receiver operating characteristic curve analysis and area under the curve (AUC) values. Postoperative outcomes, such as admission to the intensive care unit or skilled nursing facility, delirium, falls, re-hospitalization, and 30-day mortality were recorded. RESULTS: We analyzed data from 148 patients. BB thickness provided a fair prediction of frailty. Average measurements of both BB adjusted for BMI (0.708, 95% CI 0.602-0.814; P<0.001), and BSA (0.708, 95% CI 0.598-0.817; P<0.001) had the highest AUC values. RA muscle measurements could not discriminate frailty. The BMI-adjusted measurements for: right quadriceps femoris thickness (AUC 0.614, 95% CI 0.503-0.725; P=0.044), left thigh circumference (AUC 0.648, 95% CI 0.528-0.769; P=0.016), and average thigh circumference (AUC 0.630, 95% CI 0.511-0.750; P=0.033) had statistically significant but poor AUC values. CONCLUSIONS: Preoperative ultrasound measurements of the bilateral BB can fairly predict frailty in patients scheduled for total knee arthroplasty.

Incidence of Dementia and Alzheimer's Disease, Genetic Susceptibility, and Grip Strength Among Older Adults.

BACKGROUND: Grip strength has prognostic value for aging-related health outcomes. Whether the associations of grip strength with the risk of dementia and Alzheimer's disease (AD) vary by the genetic risk of AD and related dementias (ADD) is unknown. METHODS: This study included 148 659 older adults of white British ancestry (aged ≥60 years) participating in UK Biobank with no dementia, and self-reported poor health status at baseline. Polygenic risk scores (PRS) for ADD were calculated based on 64 genetic variants. Grip strength was measured by hand dynamometers. RESULTS: The hazard ratios (HR) of dementia (n = 4 963) and AD (n = 2 373) for high genetic risk of ADD were 2.36 (95% confidence interval [CI]: 2.15-2.59) and 3.00 (95% CI: 2.61-3.44), respectively, compared with low genetic risk. Compared with the bottom tertile of grip strength, the top tertile of grip strength had a hazard ratio (HR) of 0.69 (95% CI: 0.64-0.74) for incident dementia, and 0.74 (95% CI: 0.66-0.82) for incident AD, after adjustment for confounders and PRS for ADD. The risk of dementia and AD was lower with the top grip strength tertile within each level of genetic susceptibility to ADD. There was no evidence of multiplicative interaction between grip strength and genetic susceptibility to ADD for both dementia (p value: .241) and AD (p value: .314). CONCLUSIONS: Older adults with higher PRS for ADD are at higher risk of developing dementia and AD. The risk of dementia and AD was lower in individuals with higher grip strength, regardless of their level of genetic susceptibility to ADD.

Comparison of remimazolam and dexmedetomidine for intraoperative sedation in patients undergoing lower extremity surgery under spinal anesthesia: a randomized clinical trial.

BACKGROUND: Dexmedetomidine sedation has advantages, such as low incidence of respiratory depression and prolonged block duration, but also significant disadvantages, such as slow onset, high rate of sedation failure, and a long context-sensitive half-life. Remimazolam provides rapid sedation and recovery, high sedation efficacy and has minimal hemodynamic effects. We hypothesized that patients who received remimazolam would require less rescue midazolam than dexmedetomidine. METHODS: Patients (n=103) scheduled for surgery under spinal anesthesia were randomized to receive dexmedetomidine (DEX group) or remimazolam (RMZ group) targeting a Modified Observer's Assessment of Alertness/Sedation score of 3 or 4. Rescue midazolam was administered if the patient failed to be sedated after the initial loading dose or despite infusion rate adjustment. RESULTS: Rescue midazolam administration was significantly higher in the DEX group (0% vs 39.2%; p<0.001). Patients in the RMZ group reached the target sedation level more rapidly. The incidences of bradycardia (0% vs 25.5%; p<0.001) and hypertension (0% vs 21.6%; p<0.001) were higher in the DEX group. Respiratory depression occurred at a higher rate in the RMZ group (21.2% vs 2.0%; p=0.002), but no patients required manual ventilation. Patients in the RMZ group recovered faster, had a shorter PACU stay and higher satisfaction scores. Hypotensive episodes in the PACU were more frequent in the DEX group (1.9% vs 29.4%; p<0.001). CONCLUSIONS: Remimazolam showed excellent sedation efficacy, minimal hemodynamic effects, and fewer adverse events in the PACU than dexmedetomidine. However, it is important to note that respiratory depression was more frequent with the use of remimazolam. TRIAL REGISTRATION NUMBER: NCT05447507.

Replacing device-measured sedentary time with physical activity is associated with lower risk of coronary heart disease regardless of genetic risk.

BACKGROUND: Excess sedentary time (ST) is recognized as an important modifiable risk factor for coronary heart disease (CHD). However, whether the associations of genetic susceptibility with CHD incidence can be modified by replacing wearable-device-measured ST with physical activity (PA) is unknown. OBJECTIVES: To examine the associations of wearable-device-measured ST replaced by PA with incident CHD across strata of genetic susceptibility. METHODS: This study included 77,500 White British (57% female) with valid wrist-worn accelerometry and without prevalent CHD/stroke from UK Biobank. Genetic susceptibility to CHD was quantified through weighted polygenic risk scores for CHD based on 300 single-nucleotide polymorphisms. Wrist-worn accelerometer data were used to derive ST, light PA, and moderate-to-vigorous PA (MVPA). RESULTS: Reallocation of 60 min/day of ST into the same amount of MVPA was associated with approximately 9% lower relative risk of CHD for all participants and across strata of genetic risk: replacement of 1 min/day of ST associated with <1% lower relative risk of CHD. No evidence of interaction (p: 0.784) was found between genetic risk and ST for CHD risk. Reallocating 60 min/day of ST into the same MVPA time was associated with greater absolute CHD risk reductions at high genetic risk (0.27%) versus low genetic risk (0.15%). CONCLUSIONS: Replacing any amount of ST with an equal amount of MVPA time is associated with a lower relative risk of CHD, irrespective of genetic susceptibility to CHD. Reductions in CHD absolute risk for replacing ST with MVPA are greater at high genetic risk versus low genetic risk.

Noninvasive hemoglobin monitoring for maintaining hemoglobin concentration within the target range during major noncardiac surgery: A randomized controlled trial.

STUDY OBJECTIVE: The effect of noninvasive CO-oximetry hemoglobin (SpHb) monitoring on the clinical outcomes of patients undergoing surgery remains unclear. This trial aimed to evaluate whether SpHb monitoring helps maintain hemoglobin levels within a predefined target range during major noncardiac surgeries with a potential risk of intraoperative hemorrhage. DESIGN: A single-center, prospective, randomized controlled trial. SETTING: University hospital. PATIENTS: One hundred and thirty patients undergoing elective noncardiac surgery with a potential risk of hemorrhage. INTERVENTIONS: Patients were randomly allocated to undergo either SpHb-guided management (SpHb group) or usual care (control group). MEASUREMENTS: The primary outcome was the rate of deviation of the total hemoglobin concentration (determined from laboratory testing) from a pre-specified target range (8-14 g/dL). This was defined as the number of laboratory tests revealing such deviations divided by the total number of laboratory tests performed during the surgery. MAIN RESULTS: The primary outcome occurred significantly less frequently in the SpHb group as compared to that in the control group (15/555 [2.7%]) vs. 68/598 [11.4%]; relative risk, 0.24; 95% confidence interval, 0.13-0.41; P < 0.001). Fewer point-of-care blood tests were performed in the SpHb group than in the control group (median [interquartile range], 2 [1-4] vs. 4 [2-5]; P < 0.001). There were no significant intergroup differences in the number of patients who received red blood cell transfusions during surgery (SpHb vs. control, 33.8% vs. 46.2%; P = 0.201). The incidence of unnecessary red blood cell preparation (>2 units) was lower in the SpHb group than in the control group (3.1% vs. 16.9%; P = 0.024). CONCLUSIONS: Compared with routine care, SpHb-guided management resulted in significantly lower rates of hemoglobin deviation outside the target range intraoperatively in patients undergoing major noncardiac surgeries with a potential risk of hemorrhage. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT03816514).

Handheld ultrasound-assisted versus palpation-guided combined spinal-epidural for labor analgesia: a randomized controlled trial.

Preprocedural ultrasound assistance can enhance the efficacy of neuraxial anesthesia in obstetrics. We investigated whether the use of handheld ultrasound can shorten the procedural time of labor combined spinal-epidural (CSE) analgesia compared with conventional landmark-guided methods. Eighty-four women requesting labor analgesia were randomly assigned to either handheld ultrasound-assisted or palpation-guided CSE analgesia. Primary outcome was procedure time of the CSE analgesia. Secondary outcomes included identification time, performance time, number of needle manipulations required for epidural/spinal success, first-attempt success rate, periprocedural pain scores, the incidence of accidental dural puncture, and patient satisfaction. Total procedure time did not significantly differ between the ultrasound and palpation groups (median [IQR], 191.5 [167-224] vs. 204.5 [163-358] s; P = 0.442). However, the performance time was significantly shorter in the ultrasound group (134.5 [115-177] vs. 183 [129-296] s; P = 0.011), although identification time was longer in the ultrasound group (53 [41-72] vs. 30.5 [21-45] s; P < 0.001). The epidural success rate at first insertion attempt was higher in the ultrasound group (85.7% vs. 59.5%, P = 0.014). Preprocedural handheld ultrasound assistance resulted in equivalent total procedure times but reduced performance times and higher first-attempt success rates. Therefore, clinicians may consider this technique for labor CSE analgesia.Trial registration: NCT04759547.

The effects of perioperative dexmedetomidine infusion on hemodynamic stability during laparoscopic adrenalectomy for pheochromocytoma: a randomized study.

Introduction: Pheochromocytoma is a rare catecholamine-producing neuroendocrine tumor originating from the adrenal medulla chromaffin cells. Hemodynamic instability can occur during the induction of anesthesia and surgical manipulation of the tumor. This study investigated the effects of intraoperative dexmedetomidine administration on hemodynamic stability in patients undergoing laparoscopic adrenalectomy for pheochromocytoma. Methods: Forty patients who underwent laparoscopic adrenalectomy for pheochromocytoma were randomly assigned to the dexmedetomidine (n = 20) or control (n = 20) group. The primary outcome of this study was intraoperative hemodynamic stability, and the secondary endpoint was the plasma catecholamine concentrations, specifically of epinephrine and norepinephrine. Results: The intraoperative maximum blood pressures were significantly lower in the dexmedetomidine group (control vs. dexmedetomidine group: 182 ± 31 vs. 161 ± 20, 102 ± 17 vs. 90 ± 10, and 128 ± 22 vs. 116 ± 12 [mean ± SD] mmHg and p = 0.020, 0.015, and 0.040 for systolic, diastolic, and mean blood pressure, respectively). The maximum heart rate during surgery was 108 ± 15 bpm in the control group and 95 ± 12 bpm in the dexmedetomidine group (p = 0.010). Other parameters of hemodynamic instability were comparable between both groups. Plasma catecholamine concentrations did not differ between the groups. Conclusion: Dexmedetomidine infusion following the induction of anesthesia at a rate of 0.5 µg/kg/h significantly attenuated the maximum intraoperative SBP, DBP, MBP, and HR, contributing to improved hemodynamic stability.

Adherence to a healthy lifestyle, genetic susceptibility to abdominal obesity, cardiometabolic risk markers, and risk of coronary heart disease.

BACKGROUND: Little is known about whether the association between genetic susceptibility to high waist-to-hip ratio (WHR), a measure of abdominal obesity, and incident coronary heart disease (CHD) is modified by adherence to a healthy lifestyle. OBJECTIVES: To explore the interplay of genetic susceptibility to high WHR and adherence to a healthy lifestyle on incident CHD. METHODS: This study included 282,316 white British individuals from the UK Biobank study. Genetic risk for high WHR was estimated in the form of weighted polygenic risk scores (PRSs), calculated based on 156 single-nucleotide polymorphisms. Lifestyle scores were calculated based on 5 healthy lifestyle factors: regular physical activity, no current smoking, a healthy diet, <3 times/wk of alcohol consumption and 7-9 h/d of sleep. Incident CHD (n = 11,635) was accrued over a median 13.8 y of follow-up, and 12 individual cardiovascular disease risk markers assessed at baseline. RESULTS: Adhering to a favorable lifestyle (4-5 healthy factors) was associated with a 25% (hazard ratio: 0.75, 95% confidence interval: 0.70, 0.81) lower hazard of CHD compared with an unfavorable lifestyle (0-1 factor), independent of PRS for high WHR. Estimated 12-y absolute risk of CHD was lower for a favorable lifestyle at high genetic risk (1.73%) and medium genetic risk (1.67%) than for an unfavorable lifestyle at low genetic risk (2.08%). Adhering to a favorable lifestyle was associated with healthier levels of cardiovascular disease risk markers (except random glucose and high-density lipoprotein), independent of PRS for high WHR. CONCLUSIONS: Individuals who have high or medium genetic risk of abdominal obesity but adhere to a healthy lifestyle may have a lower risk of developing CHD, compared with those who have low genetic risk and an unhealthy lifestyle. Future clinical trials of lifestyle modification could be implemented for individuals at high genetic risk of abdominal obesity for the primary prevention of CHD events.

Independent and joint associations of aerobic and muscle-strengthening exercise with mental health in adolescents: A cross-sectional analysis before and during COVID-19 using the 2015-2021 National Youth Risk Behavior Survey.

PURPOSE: COVID-19 led to social isolation that may have compromised adolescent mental health. This study examined the independent and joint associations of aerobic physical activity (PA) and muscle-strengthening exercise (MSE) with mental health problems in adolescents. METHODS: Participants were US adolescents who completed the 2015-2021 National Youth Risk Behavior Survey (N = 61,298; 45.7% female). Data were collected between 2015 and 2021 and analyzed in 2023. Outcomes were binary response items asking about feeling sad/hopeless, having difficulty concentrating, remembering, or making decisions, and having a suicidal ideation. Preventive exposure variables were items asking about frequencies of aerobic PA and MSE with responses dichotomized to align with recommendations. Independent and joint associations were examined using robust Poisson regression with covariates selected using double selection lasso. Structural equation models examined the associations treating PA and MSE as continuous predictors and poor mental health as a latent dependent variable. RESULTS: Meeting either recommendation alone associated with a 4-10% lower prevalence of mental health problems (APR = 0.90-0.96, p < 0.05), and meeting both recommendations associated with a 15%-20% lower prevalence of mental health problems (APR = 0.80-0.85, p < 0.001). Although categorical joint associations were stronger in males (p < 0.05), multiplicative interactions were observed in females using continuous variables for PA and MSE (ß = -0.09, p < 0.001). CONCLUSION: Meeting aerobic PA and MSE recommendations associated with lower prevalence of mental health problems. Participation in MSE below recommended levels may be beneficial for females when combined with aerobic PA. Future research should examine these associations by acquiring contextual information and device-based assessments.

Comparison between low-volume local anesthetic with intravenous dexamethasone and conventional volume without dexamethasone for superior trunk block after arthroscopic shoulder surgery: a randomized controlled non-inferiority trial.

INTRODUCTION: This study aimed to investigate whether low-volume local anesthetic with intravenous dexamethasone can reduce the incidence of diaphragmatic paresis while maintaining the analgesic duration compared with conventional volume of local anesthetic without intravenous dexamethasone when performing ultrasound-guided superior trunk block in patients undergoing arthroscopic shoulder surgery. METHODS: Eighty-four adult patients undergoing arthroscopic shoulder surgery under general anesthesia were randomly assigned to receive ultrasound-guided superior trunk block using 7 mL of 0.5% ropivacaine with 0.15 mg/kg of intravenous dexamethasone (treatment group), or 15 mL of 0.5% ropivacaine with intravenous normal saline (control group). The co-primary outcomes were (1) the duration of analgesia (time between block completion and onset of surgical pain with a Numeric Rating Scale pain score of 4 or higher), which was compared against a non-inferiority margin of 3 hours, and (2) the incidence of diaphragmatic paresis evaluated using M-mode ultrasonography in the post-anesthesia care unit. RESULTS: The mean duration of analgesia was 12.4 (6.8) and 11.2 (4.6) hours in the treatment and control groups, respectively (mean difference: -1.2 hours; 95% CI -3.8 to 1.3]; p for non-inferiority<0.001), meeting the non-inferiority criteria. The incidence of diaphragmatic paresis was 45.2% and 85.4% in the treatment and control groups, respectively (relative risk: 0.53; 97.5% CI 0.35 to 0.80; p<0.001). CONCLUSIONS: Superior trunk block using low-volume local anesthetic with intravenous dexamethasone can reduce the incidence of diaphragmatic paresis while providing non-inferior analgesic duration compared with the conventional volume of local anesthetic in patients undergoing arthroscopic shoulder surgery. TRIAL REGISTRATION NUMBER: Clinical Research Information Service of Republic of Korea Registry (KCT0005998).

Anterior quadratus lumborum block for analgesia after living-donor renal transplantation: a double-blinded randomized controlled trial.

INTRODUCTION: Limited non-opioid analgesic options are available for managing postoperative pain after renal transplantation. We aimed to investigate whether the unilateral anterior quadratus lumborum (QL) block would reduce postoperative opioid consumption after living-donor renal transplantation in the context of multimodal analgesia. METHODS: Eighty-eight adult patients undergoing living-donor renal transplantation were randomly allocated to receive the unilateral anterior QL block (30 mL of ropivacaine 0.375%) or sham block (normal saline) on the operated side before emergence from anesthesia. All patients received standard multimodal analgesia, including the scheduled administration of acetaminophen and fentanyl via intravenous patient-controlled analgesia. The primary outcome was the total opioid consumption during the first 24 hours after transplantation. The secondary outcomes included pain scores, time to first opioid administration, cutaneous distribution of sensory blockade, motor weakness, nausea/vomiting, quality of recovery scores, time to first ambulation, and length of hospital stay. RESULTS: The total opioid consumption in the first 24 hours after transplantation did not differ significantly between the intervention and control groups (median (IQR), 160.5 (78-249.8) vs 187.5 (93-309) oral morphine milligram equivalent; median difference (95% CI), -27 (-78 to 24), p=0.29). No differences were observed in the secondary outcomes. CONCLUSIONS: The anterior QL block did not reduce opioid consumption in patients receiving multimodal analgesia after living-donor renal transplantation. Our findings do not support the routine administration of the anterior QL block in this surgical population. TRIAL REGISTRATION NUMBER: NCT04908761.

Mode of transport, genetic susceptibility, and incidence of coronary heart disease.

BACKGROUND: Car use has been associated with higher risk of coronary heart disease (CHD). However, whether the associations of transport modes with CHD vary by genetic susceptibility to CHD are unknown. This study aims to investigate the associations of genetic susceptibility and modes of transport with incidence of CHD. METHODS: We included 339,588 white British participants from UK Biobank with no history of CHD or stroke at baseline or within two years of follow-up (52.3% in work). Genetic susceptibility to CHD was quantified through weighted polygenic risk scores derived from 300 single-nucleotide polymorphisms related to CHD risk. Categories of transport mode included exclusive car use and alternatives to the car (e.g., walking, cycling and public transport), separately for non-commuting (e.g., getting about [n=339,588] excluding commuting for work), commuting (in the sub-set in work [n=177,370] who responded to the commuting question), and overall transport (transport mode for both commuting and non-commuting [n=177,370]). We used Cox regression with age as the underlying timescale to estimate hazard ratios (HR) of CHD (n=13,730; median 13.8-year follow-up) and tested the interaction between genetic susceptibility and travel modes with adjustment for confounders. RESULTS: Compared to those using alternatives to the car, hazards of CHD were higher for exclusive use of cars for overall transport (HR: 1.16, 95% confidence interval (CI): 1.08-1.25), non-commuting (HR: 1.08, 95% CI: 1.04-1.12) and commuting (HR: 1.16, 95% CI: 1.09-1.23), after adjusting for confounders plus genetic susceptibility. HRs of CHD were 1.45 (95% CI: 1.38-1.52) and 2.04 (95% CI: 1.95-2.12) for the second and third tertile of genetic susceptibility to CHD, respectively, compared to the first. There was, in general, no strong evidence of interactions between genetic susceptibility and categories of overall, non-commuting and commuting transport. Estimated 10-year absolute risk of CHD was lower for the alternatives to the car across strata of genetic susceptibility, compared with exclusive use of cars for overall, non-commuting and commuting transport. CONCLUSION: Exclusive use of cars was associated with a relatively higher risk of CHD across all strata of genetic susceptibility. Using alternatives to the car should be encouraged for prevention of CHD for the general population including individuals at high genetic risk.

Laser guidance for ultrasound-guided radial artery catheterization using smart glasses: a randomized trial.

PURPOSE: The use of smart glasses during ultrasound-guided needle procedures may reduce operators' head movements but has not been shown to improve procedural performance. Laser guidance has been shown to decrease the time required for ultrasound-guided procedures in phantom models but has not been tested clinically. We hypothesized that adding laser guidance to the use of smart glasses for ultrasound-guided radial artery catheterization using the long axis approach would improve performance by relatively inexperienced users unfamilar with these techniques. METHODS: In an unblinded controlled trial, we enrolled 52 patients requiring radial artery catheterization under anesthesia, randomized into two groups: smart glasses only (SO) (control; N = 26) or smart glasses with laser guidance group (SL) (N = 26). We assessed catheterization time (primary outcome), the number of needle redirections, first-pass success rate, and operator satisfaction (100 = most satisfactory; 0 = unsatisfactory). RESULTS: Comparing the SL with the SO group, catheterization time was shorter (median [interquartile range], 13 [9-20] sec vs 24 [18-46] sec, P < 0.001) and the number of needle redirections was lower (0 [0-1] vs 3 [1-3], P < 0.001) while the first-pass success rate (50% vs 12%, P = 0.007) and operator satisfaction score (85 [76-95] vs 52 [44-74], P < 0.001) were higher. CONCLUSION: Laser guidance improved the performance of ultrasound-guided radial artery catheterization using smart glasses in users inexperienced in the long axis in-plane approach. Nevertheless, it is unclear whether these findings are clinically significant. STUDY REGISTRATION DATE: CRIS.nih.go.kr (KCT0007168); registered 8 April 2022.

RéSUMé: OBJECTIF: L'utilisation de lunettes intelligentes pendant les procédures de ponctions échoguidées peut réduire les mouvements de la tête des opérateurs et opératrices, mais il n'a pas été démontré qu'elle améliorait les performances procédurales. Il a été démontré que le guidage laser réduisait le temps requis pour les interventions échoguidées sur des modèles fantômes, mais cette modalité n'a pas été testée cliniquement. Nous avons émis l'hypothèse que l'ajout d'un guidage laser à l'utilisation de lunettes intelligentes pour le cathétérisme échoguidé de l'artère radiale en utilisant une approche longitudinale (long axe) améliorerait les performances d'utilisateurs et utilisatrices relativement inexpérimenté·es et peu familier·ères avec ces techniques. MéTHODE: Dans une étude contrôlée sans insu, nous avons recruté et randomisé en deux groupes 52 patient·es nécessitant un cathétérisme de l'artère radiale sous anesthésie : lunettes intelligentes uniquement (LIU) (témoin N = 26) ou lunettes intelligentes avec guidage laser (LIL) (N = 26). Nous avons évalué le temps de cathétérisme (critère d'évaluation principal), le nombre de réorientation d'aiguilles, le taux de réussite au premier passage et la satisfaction de l'opérateur·trice (100 = le plus satisfaisant; 0 = insatisfaisant). RéSULTATS: En comparant le groupe LIL au groupe LIU, le temps de cathétérisme était plus court (médiane [écart interquartile], 13 [9-20] sec vs 24 [18­46] sec, P < 0,001) et le nombre de réorientations d'aiguilles était plus faible (0 [0­1] vs 3 [1­3], P < 0,001), tandis que le taux de réussite au premier passage (50 % vs 12 %, P = 0,007) et le score de satisfaction des opératrices et opérateurs (85 [76­95] vs 52 [44­74], P < 0,001) étaient plus élevés. CONCLUSION: Le guidage laser à l'aide de lunettes intelligentes a amélioré les performances du cathétérisme échoguidé de l'artère radiale chez des utilisateurs et utilisatrices inexpérimenté·es en approche longitudinale. Nous ne pouvons toutefois pas déterminer si ces résultats sont cliniquement significatifs. DATE D'ENREGISTREMENT DE L'éTUDE: CRIS.nih.go.kr (KCT0007168); enregistré le 8 avril 2022.

Influence of laminectomy on the lumbosacral cerebrospinal fluid volume: A retrospective magnetic resonance imaging study.

The cerebrospinal fluid volume affects the block height of spinal anaesthesia. Laminectomy of the lumbar spine may result in increased lumbosacral cerebrospinal fluid volume. This study aimed to test the hypothesis that the lumbosacral cerebrospinal fluid volume of patients with a history of lumbar laminectomy would be larger than that of patients with normal lumbar spine anatomy using magnetic resonance imaging. Lumbosacral spine magnetic resonance images of 147 patients who underwent laminectomy at the L2 vertebrae or below (laminectomy group) and 115 patients without a history of spinal surgery (control group) were retrospectively reviewed. The lumbosacral cerebrospinal fluid volumes between the L1-L2 intervertebral disc level and the end of the dural sac were measured and compared between the two groups. The mean (standard deviation) lumbosacral cerebrospinal fluid volume was 22.3 (7.8) ml and 21.1 (7.4) ml in the laminectomy and control groups, respectively (mean difference 1.2 ml; 95% confidence interval -0.7 to 3.0 ml; P = 0.218). In the prespecified subgroup analysis according to the number of laminectomy levels, patients who underwent more than two levels of laminectomy exhibited slightly larger lumbosacral cerebrospinal fluid volume (n = 17, 30.5 (13.5) ml) compared with those who underwent two (n = 40, 20.7 (5.6) ml; P = 0.014) or one level of laminectomy (n = 90, 21.4 (6.2) ml; P = 0.010) and the control group (21.1 (7.4) ml; P = 0.012). In conclusion, the lumbosacral cerebrospinal fluid volume did not differ between patients who underwent lumbar laminectomy and those without a history of laminectomy. However, patients who underwent laminectomy at more than two levels had a slightly larger volume of lumbosacral cerebrospinal fluid than those who underwent less extensive laminectomy and those without a history of lumbar spine surgery. Further studies are warranted to confirm the subgroup analysis findings and elucidate the clinical implications of such differences in the lumbosacral cerebrospinal fluid volume.

Endolysosomal impairment by binding of amyloid beta or MAPT/Tau to V-ATPase and rescue via the HYAL-CD44 axis in Alzheimer disease.

Impaired activities and abnormally enlarged structures of endolysosomes are frequently observed in Alzheimer disease (AD) brains. However, little is known about whether and how endolysosomal dysregulation is triggered and associated with AD. Here, we show that vacuolar ATPase (V-ATPase) is a hub that mediates proteopathy of oligomeric amyloid beta (Aß) and hyperphosphorylated MAPT/Tau (p-MAPT/Tau). Endolysosomal integrity was largely destroyed in Aß-overloaded or p-MAPT/Tau-positive neurons in culture and AD brains, which was a necessary step for triggering neurotoxicity, and treatments with acidic nanoparticles or endocytosis inhibitors rescued the endolysosomal impairment and neurotoxicity. Interestingly, we found that the lumenal ATP6V0C and cytosolic ATP6V1B2 subunits of the V-ATPase complex bound to the internalized Aß and cytosolic PHF-1-reactive MAPT/Tau, respectively. Their interactions disrupted V-ATPase activity and accompanying endolysosomal activity in vitro and induced neurodegeneration. Using a genome-wide functional screen, we isolated a suppressor, HYAL (hyaluronidase), which reversed the endolysosomal dysfunction and proteopathy and alleviated the memory impairment in 3xTg-AD mice. Further, we found that its metabolite hyaluronic acid (HA) and HA receptor CD44 attenuated neurotoxicity in affected neurons via V-ATPase. We propose that endolysosomal V-ATPase is a bona fide proteotoxic receptor that binds to pathogenic proteins and deteriorates endolysosomal function in AD, leading to neurodegeneration in proteopathy.Abbreviations: AAV, adeno-associated virus; Aß, amyloid beta; AD, Alzheimer disease; APP, amyloid beta precursor protein; ATP6V0C, ATPase H+ transporting V0 subunit c; ATP6V1A, ATPase H+ transporting V1 subunit A; ATP6V1B2, ATPase H+ transporting V1 subunit B2; CD44.Fc, CD44-mouse immunoglobulin Fc fusion construct; Co-IP, co-immunoprecipitation; CTSD, cathepsin D; HA, hyaluronic acid; HMWHA, high-molecular-weight hyaluronic acid; HYAL, hyaluronidase; i.c.v, intracerebroventricular; LMWHA, low-molecular-weight hyaluronic acid; NPs, nanoparticles; p-MAPT/Tau, hyperphosphorylated microtubule associated protein tau; PI3K, phosphoinositide 3-kinase; V-ATPase, vacuolar-type H+-translocating ATPase; WT, wild-type.

Pathogenic Role of RAGE in Tau Transmission and Memory Deficits.

BACKGROUND: In tauopathies, brain regions with tau accumulation strongly correlate with clinical symptoms, and spreading of misfolded tau along neural network leads to disease progression. However, the underlying mechanisms by which tau proteins enter neurons during pathological propagation remain unclear. METHODS: To identify membrane receptors responsible for neuronal propagation of tau oligomers, we established a cell-based tau uptake assay and screened complementary DNA expression library. Tau uptake and propagation were analyzed in vitro and in vivo using a microfluidic device and stereotactic injection. The cognitive function of mice was assessed using behavioral tests. RESULTS: From a genome-wide cell-based functional screening, RAGE (receptor for advanced glycation end products) was isolated to stimulate the cellular uptake of tau oligomers. Rage deficiency reduced neuronal uptake of pathological tau prepared from rTg4510 mouse brains or cerebrospinal fluid from patients with Alzheimer's disease and slowed tau propagation between neurons cultured in a 3-chamber microfluidic device. RAGE levels were increased in the brains of rTg4510 mice and tau oligomer-treated neurons. Rage knockout decreased tau transmission in the brains of nontransgenic mice after injection with Alzheimer's disease patient-derived tau and ameliorated memory loss after injection with GFP-P301L-tau-AAV. Treatment of RAGE antagonist FPS-ZM1 blocked transsynaptic tau propagation and inflammatory responses and alleviated cognitive impairment in rTg4510 mice. CONCLUSIONS: These results suggest that in neurons and microglia, RAGE binds to pathological tau and facilitates neuronal tau pathology progression and behavioral deficits in tauopathies.