Low-intensity pulsed ultrasound improves symptoms in patients with Buerger disease: a double-blinded, randomized, and placebo-controlled study.

Here we report the effects of low-intensity pulsed ultrasound (LIPUS) on symptoms in peripheral arterial disease patients with Buerger disease. A double-blinded and randomized study with active and inactive LIPUS was conducted. We assessed symptoms in leg circulation during a 24-week period of LIPUS irradiation in 12 patients with Buerger disease. Twelve patients without LIPUS irradiation served as controls. The pain intensity on visual analog score was significantly decreased after 24-week LIPUS treatment. Skin perfusion pressure was significantly increased in patients who received LIPUS treatment. There was no significant difference in symptoms and perfusion parameters in the control group. No severe adverse effects were observed in any of the patients who underwent LIPUS treatment. LIPUS is noninvasive, safe and effective option for improving symptoms in patients with Buerger disease.

The Number of Microbubbles Generated During Cardiopulmonary Bypass Can Be Estimated Using Machine Learning From Suction Flow Rate, Venous Reservoir Level, Perfusion Flow Rate, Hematocrit Level, and Blood Temperature.

GOAL: Microbubbles (MBs) are known to occur within the circuits of cardiopulmonary bypass (CPB) systems, and higher-order dysfunction after cardiac surgery may be caused by MBs as well as atheroma dispersal associated with cannula insertion. As complete MB elimination is not possible, monitoring MB count rates is critical. We propose an online detection system with a neural network-based model to estimate MB count rate using five parameters: suction flow rate, venous reservoir level, perfusion flow rate, hematocrit level, and blood temperature. METHODS: Perfusion experiments were performed using an actual CPB circuit, and MB count rates were measured using the five varying parameters. RESULTS: Bland-Altman analysis indicated a high estimation accuracy (R2 > 0.95, p < 0.001) with no significant systematic error. In clinical practice, although the inclusion of clinical procedures slightly decreased the estimation accuracy, a high coefficient of determination for 30 clinical cases (R2 = 0.8576) was achieved between measured and estimated MB count rates. CONCLUSIONS: Our results highlight the potential of this system to improve patient outcomes and reduce MB-associated complication risk.

Simultaneous Control of Venous Reservoir Level and Arterial Flow Rate in Cardiopulmonary Bypass With a Centrifugal Pump.

Cardiopulmonary bypass (CPB) is an indispensable technique in cardiac surgery, providing the ability to temporarily replace cardiopulmonary function and create a bloodless surgical field. Traditionally, the operation of CPB systems has depended on the expertise and experience of skilled perfusionists. In particular, simultaneously controlling the arterial and venous occluders is difficult because the blood flow rate and reservoir level both change, and failure may put the patient's life at risk. This study proposes an automatic control system with a two-degree-of-freedom model matching controller nested in an I-PD feedback controller to simultaneously regulate the blood flow rate and reservoir level. CPB operations were performed using glycerin and bovine blood as perfusate to simulate flow-up and flow-down phases. The results confirmed that the arterial blood flow rate followed the manually adjusted target venous blood flow rate, with an error of less than 5.32%, and the reservoir level was maintained, with an error of less than 3.44% from the target reservoir level. Then, we assessed the robustness of the control system against disturbances caused by venting/suction of blood. The resulting flow rate error was 5.95%, and the reservoir level error 2.02%. The accuracy of the proposed system is clinically satisfactory and within the allowable error range of 10% or less, meeting the standards set for perfusionists. Moreover, because of the system's simple configuration, consisting of a camera and notebook PC, the system can easily be integrated with general CPB equipment. This practical design enables seamless adoption in clinical settings. With these advancements, the proposed system represents a significant step towards the automation of CPB.

Neural Network-based Estimation of Microbubbles Generated in Cardiopulmonary Bypass Circuit: A Clinical Application Study.

The cardiopulmonary bypass system used in cardiac surgery can generate microbubbles (MBs) that may cause complications, such as neurocognitive dysfunction, when delivered into the blood vessel. Estimating the number of MBs generated, thus, is necessary to enable the surgeons to deal with it. To this end, we previously proposed a neural network-based model for estimating the number of MBs from four factors measurable from the cardiopulmonary bypass system: suction flow rate, venous reservoir level, blood viscosity, and perfusion flow rate. However, the model has not been adapted to the data collected from actual surgery cases. In this study, the accuracy of MBs estimated by the proposed model was examined in four clinical cases. The results showed that the coefficient of determination between estimated MBs and the measured MBs throughout the surgeries was R2=0.558 (p<0.001). We found that the surgical treatments, such as administration of drugs, fluids and blood transfusions, increased the number of measured MBs. The coefficient of determination increased to R2= 0.8762 (p<0.001) by excluding the duration of these treatments. This result indicates that the model can estimate the number of MBs with high accuracy under the clinical environment.

Increased cerebrovascular reactivity in selected brain regions after extracranial-intracranial bypass improves the speed and accuracy of visual cancellation in patients with severe steno-occlusive disease: a preliminary study.

The effect of the change in cerebrovascular reactivity (CVR) in each brain area on cognitive function after extracranial-intracranial bypass (EC-IC bypass) was examined. Eighteen patients who underwent EC-IC bypass for severe unilateral steno-occlusive disease were included. Single-photon emission CT (SPECT) for evaluating CVR and the visual cancellation (VC) task were performed before and after surgery. The accuracy of VC was expressed by the arithmetic mean of the age-matched correct answer rate and the accurate answer rate, and the averages of the time (time score) and accuracy (accuracy score) of the four VC subtests were used. The speed of VC tended to be slower, whereas accuracy was maintained before surgery. The EC-IC bypass improved CVR mainly in the cerebral hemisphere on the surgical side. On bivariate analysis, when CVR increased post-operatively, accuracy improved on both surgical sides, but the time score was faster on the left and slower on the right surgical side. Stepwise multiple regression analysis showed that the number of the brain regions associated with the time score was 5 and that associated with the accuracy score was 4. In the hemodynamically ischemic brain, processing speed might be adjusted so that accuracy would be maintained based on the speed-accuracy trade-off mechanism that may become engaged separately in the left and right cerebral hemispheres when performing VC. When considering the treatment for hemodynamic ischemia, the relationship between CVR change and the speed-accuracy trade-off in each brain region should be considered.

Prediction of blood pressure change during surgical incision under opioid analgesia using sympathetic response evoking threshold.

Opioid inhibition of nociceptive stimuli varies in individuals and is difficult to titrate. We have reported the vascular stiffness value (K) as a standard monitor to quantify sympathetic response with high accuracy. On the contrary, among individuals, a considerable variation in the rate of change in K for constant pain has been observed. In this study, we proposed a new index, the minimum stimulus intensity value that evoked the response on K (MECK: Minimum Evoked Current of K), and evaluated its accuracy in predicting sympathetic response to nociceptive stimuli under constant opioid administration. Thirty patients undergoing open surgery under general anesthesia were included. After anesthetic induction, remifentanil was administered at a constant concentration of 2 ng/ml at the effect site followed by tetanus stimulation. MECK was defined as the minimal current needed to produce a change in K. MECK significantly (P < 0.001) correlated with the rate of change of systolic blood pressure during skin incision (ROCBP). Bland-Altman plot analysis using the predicted ROCBP calculated from MECK and the measured ROCBP showed that the prediction equation for ROCBP was highly accurate. This study showed the potential of MECK to predict blood pressure change during surgical incision under opioid analgesia.Clinical trial registration Registry: University hospital medical information network; Registration number: UMIN000041816; Principal investigator's name: Satoshi Kamiya; Date of registration: July 9th, 2019.

Neural network-based modeling of the number of microbubbles generated with four circulation factors in cardiopulmonary bypass.

The need for the estimation of the number of microbubbles (MBs) in cardiopulmonary bypass surgery has been recognized among surgeons to avoid postoperative neurological complications. MBs that exceed the diameter of human capillaries may cause endothelial disruption as well as microvascular obstructions that block posterior capillary blood flow. In this paper, we analyzed the relationship between the number of microbubbles generated and four circulation factors, i.e., intraoperative suction flow rate, venous reservoir level, continuous blood viscosity and perfusion flow rate in cardiopulmonary bypass, and proposed a neural-networked model to estimate the number of microbubbles with the factors. Model parameters were determined in a machine-learning manner using experimental data with bovine blood as the perfusate. The estimation accuracy of the model, assessed by tenfold cross-validation, demonstrated that the number of MBs can be estimated with a determinant coefficient R2 = 0.9328 (p < 0.001). A significant increase in the residual error was found when each of four factors was excluded from the contributory variables. The study demonstrated the importance of four circulation factors in the prediction of the number of MBs and its capacity to eliminate potential postsurgical complication risks.

A new arterial mechanical property indicator reflecting differences in invasive stimulus intensity induced by alteration of remifentanil concentration during laryngoscopy.

BACKGROUND: Reliable analgesia monitoring is not available for general anaesthesia cases. In 2003, we introduced a method to characterise arterial mechanical properties, which we termed arterial stiffness (K). However, it is unclear whether differences in K actually indicate changes in the intensity of a noxious stimulus. Thus, we examined the relationship between stress intensity and the value of K. METHODS: Thirty patients under general anesthesia were randomly divided into two remifentanil concentration groups (2 and 6 ng/mL). After a steady concentration of remifentanil was achieved for at least 3 minutes, laryngoscopy was performed. After completion of laryngoscopy, once the K value returned to near-baseline, laryngoscopy with endotracheal intubation was performed, and the value of K after the procedure was recorded and analyzed. RESULTS: In total, data were obtained for 28 of 30 patients. The values of K before the laryngoscopy were not significantly different between the groups (2 ng/mL group: 13.1 [8.5-33.1] mmHg/%; 6 ng/mL group: 11.6 [4.3-31.4] mmHg/%; P=0.53). After laryngoscopy, K was approximately 2 times greater in the 2 ng/mL group than in the 6 ng/mL group (39.0 [13.6-115.9] mmHg/% vs. 19.0 [5.5-85.1] mmHg/%, P=0.02). After intubation also, K was approximately 2 times greater in the 2 ng/mL group (52.0 [27.7-122.0] mmHg/% vs. 24.3 [7.2-94.9] mmHg/%, P=0.04). CONCLUSIONS: The value for arterial stiffness (K) non-proportionally changes in response to stimulus intensity; therefore, it has the potential to be used as an indicator of nociceptive stimulation intensity.

Predicting ischemic stroke after carotid artery stenting based on proximal calcification and the jellyfish sign.

OBJECTIVE Carotid artery stenting (CAS) has been considered to prevent ischemic strokes caused by stenosis of the cervical carotid artery. The most common complication of CAS is new cerebral infarction. The authors have previously reported that the jellyfish sign-the rise and fall of the mobile component of the carotid plaque surface detected by carotid ultrasonography-suggests thinning and rupture of the fibrous cap over the unstable plaque content, such as the lipid-rich necrotic core or internal plaque hemorrhage. The authors' aim in the present study was to evaluate the risk of a new ischemic lesion after CAS by using many risk factors including calcification (size and location) and the jellyfish sign. METHODS Eighty-six lesions (77 patients) were treated with CAS. The presence of ischemic stroke was determined using diffusion-weighted imaging (DWI). Risk factors included calcification of the plaque (classified into 5 groups for size and 3 groups for location) and the jellyfish sign, among others. Multiple linear regression analysis (stepwise analysis and partial least squares [PLS] analysis) was conducted, followed by a machine learning analysis using an artificial neural network (ANN) based on the log-linearized gaussian mixture network (LLGMN). The additive effects of the jellyfish sign and calcification on ischemic stroke after CAS were examined using the Kruskal-Wallis test, followed by the Steel-Dwass test. RESULTS The stepwise analysis selected the jellyfish sign, proximal calcification (proximal Ca), low-density lipoprotein (LDL) cholesterol, and patient age for the prediction model to predict new DWI lesions. The PLS analysis revealed the same top 3 variables (jellyfish sign, proximal Ca, and LDL cholesterol) according to the variable importance in projection scores. The ANN was then used, showing that these 3 variables remained. The accuracy of the ANN improved; areas under the receiver operating characteristic curves of the stepwise analysis, the PLS analysis, and the ANN were 0.719, 0.727, and 0.768, respectively. The combination of the jellyfish sign and proximal Ca indicates a significantly increased risk for ischemic stroke after CAS. CONCLUSIONS The jellyfish sign, proximal Ca, and LDL cholesterol were considered to be important predictors for new DWI lesions after CAS. These 3 factors can be easily determined during a standard clinical visit. Thus, these 3 variables-especially the jellyfish sign and proximal Ca-may be useful for reducing the ischemic stroke risk in patients with stenosis of the cervical carotid artery.

Endothelial Function Assessed by Automatic Measurement of Enclosed Zone Flow-Mediated Vasodilation Using an Oscillometric Method Is an Independent Predictor of Cardiovascular Events.

BACKGROUND: A new device for automatic measurement of flow-mediated vasodilation (FMD) using an oscillometric method has been developed to solve technical problems of conventional FMD measurement. This device measures enclosed zone FMD (ezFMD). The purpose of this study was to evaluate the prognostic value of endothelial function assessed by ezFMD for future cardiovascular events. METHODS AND RESULTS: We measured ezFMD in 272 participants who underwent health-screening examinations. First, we investigated cross-sectional associations between ezFMD and cardiovascular risk factors, and then we assessed the associations between ezFMD and first major cardiovascular events (death from cardiovascular causes, stroke, and coronary revascularization). Univariate regression analysis revealed that ezFMD was significantly correlated with age, triglycerides, glucose, smoking pack-years, estimated glomerular filtration rate, high-sensitivity C-reactive protein, and Framingham risk score. During a median follow-up period of 36.1 months (interquartile range 18.8-40.1 months), 12 participants died (6 from cardiovascular causes), 3 had stroke, 8 had coronary revascularization, and 10 were hospitalized for heart failure. There was no episode of acute coronary syndrome during the study period. Participants were divided into tertiles (low, intermediate, and high) based on ezFMD. Kaplan-Meier curves for first major cardiovascular events among the 3 groups were significantly different (P=0.004). After adjustment for cardiovascular risk factors, the low group was significantly associated with an increased risk of first major cardiovascular events compared with the high group (hazard ratio 6.47; 95% CI 1.09-125.55; P=0.038). CONCLUSIONS: These findings suggest that endothelial function assessed by ezFMD may be useful as a surrogate marker of future cardiovascular events. CLINICAL TRIAL REGISTRATION: URL: https://upload.umin.ac.jp. Unique identifier: UMIN000004902.

A blood viscosity estimation method based on pressure-flow characteristics of an oxygenator during cardiopulmonary bypass and its clinical application.

In this paper, we developed a model that uses pressure-flow monitoring information in the oxygenator to estimate viscosity of human blood. The comparison between estimated viscosity (ηe) and measured viscosity (η) was assessed in 16 patients who underwent cardiac surgery using mild hypothermia cardiopulmonary bypass (CPB). After initiation of CPB, ηe was recorded at three periods: post-establishment of total CPB, post-aortic cross-clamp, and post-declamp. During the same period, blood samples were collected from the circuit and η was measured with a torsional oscillation viscometer. The ηe was plotted as a function of η and the systematic errors and compatibility between two methods were assessed using Bland-Altman analysis. The parameters ηe and η were very strongly correlated at all points (R(2)=0.9616, p<;0.001). The Bland-Altman analysis revealed a mean bias of -0.001 mPas, a standard deviation of 0.03 mPas, limits of agreement of -0.06 mPas to 0.06 mPas, and a percent error of 3.3%. There was no fixed bias or proportion bias for the viscosity. As this method estimates blood viscosity with good precision during CPB continuously, it may be helpful for clinical perfusion management.

A novel noninvasive and simple method for assessment of endothelial function: enclosed zone flow-mediated vasodilation (ezFMD) using an oscillation amplitude measurement.

BACKGROUND: It is clinically important to estimate the degree of endothelial dysfunction. Several methods have been used to assess endothelial function in humans. Recently, we developed a new noninvasive method for measurement of vascular response to reactive hyperemia in the brachial artery, named enclosed zone flow-mediated vasodilation (ezFMD). The purpose of this study was to determine the validity of ezFMD for assessment of endothelial function. METHODS AND RESULTS: We measured ezFMD by a new device using an oscillometric method and conventional FMD using ultrasonography in 306 subjects, including patients with hypertension, dyslipidemia, and diabetes mellitus (218 men and 88 women, 30 ± 16 yr). Univariate regression analysis revealed that ezFMD significantly correlated with age (r = -0.42, P < 0.0001), body mass index (r = -0.13, P = 0.028), systolic blood pressure (r = -0.15, P = 0.009), diastolic blood pressure (r = -0.14, P = 0.011), fasting glucose level (r = -0.27, P = 0.006), smoking (r = -0.21, P = 0.007) and baseline pulse wave amplitude (r = -0.51, P < 0.0001). ezFMD significantly correlated with conventional FMD (r = 0.34, P < 0.0001). Multiple regression analysis revealed that age (P = 0.002), body mass index (P = 0.013), systolic blood pressure (P = 0.009), smoking (P = 0.004) and baseline pulse wave amplitude (P < 0.001) were independent predictors of ezFMD. CONCLUSIONS: These findings suggest that measurement of ezFMD, a novel noninvasive and simple method, may be useful for determination of vascular diameter response to reactive hyperemia. Since ezFMD is automatically measured by a device with an oscillometric method, measurement of ezFMD is easier and less biased than that of conventional FMD.

A novel online method to monitor autonomic nervous activity based on arterial wall impedance and heart rate variability.

This paper proposes a new method of evaluating autonomic nervous activity using the mechanical impedance of arterial walls and heart rate variability. The cardiovascular system is indispensable to life maintenance functions, and homeostasis is maintained by the autonomic nervous system. Accordingly, it is very important to be able to make diagnosis based on autonomic nervous activity within the body's circulation. The proposed method was evaluated in surgical operations; the mechanical impedance of the arterial wall was estimated from arterial blood pressure and a photoplethysmogram, and heart rate variability was estimated using electrocardiogram R-R interval spectral analysis. In this paper, we monitored autonomic nervous system activity using the proposed system during endoscopic transthoracic sympathetic block surgery in eight patients with hyperhidrosis. The experimental results indicated that the proposed system can be used to estimate autonomic nervous activity in response to events during operations.

Effects of ionizing radiation on locomotory behavior and mechanosensation in Caenorhabditis elegans.

Locomotory behavior (motility) and mechanosensation are of vital importance in animals. We examined the effects of ionizing radiation (IR) on locomotory behavior and mechanosensation using a model organism, the nematode Caenorhabditis elegans. Bacterial mechanosensation in C. elegans induces the dopamine-mediated slowing of locomotion in the presence of bacteria (food), known as the basal slowing response. We previously reported an IR-induced reduction of locomotory rate in the absence of food. In the present study, we observed a similar IR-induced reduction of locomotory rate in the cat-2 mutant, which is defective in bacterial mechanosensation. The dose response pattern of the locomotory rate in the presence of food was relatively flat in wild-type animals, but not in cat-2 mutants. This suggests that the dopamine system, which is related to bacterial mechanosensation in C. elegans, might have a dominant effect on locomotory rate in the presence of food, which masks the effects of other stimuli. Moreover, we found that the behavioral responses of hydrogen peroxide-exposed wild-type animals are similar to those of IR-exposed animals. Our findings suggest that the IR-induced reduction of locomotory rate in the absence of food is mediated by a different pathway from that for bacterial mechanosensation, at least partially through IR-produced hydrogen peroxide.

Arterial mechanical impedance is a sensitive stress response monitor during general anesthesia.

Arterial mechanical impedance is a characteristic of arterial dynamics that is determined by photoplethysmographic amplitude and direct arterial pressure, while mechanical impedance is indicated by stiffness, viscosity, and inertia. We compared the parameters of mechanical impedance and photoplethysmographic amplitude to estimate the magnitude of stress response in patients undergoing general anesthesia by measuring direct arterial pressure. After sedating each patient with propofol, photoplethysmographic amplitude and mechanical impedance were measured as baseline control values, then 3 min after fentanyl administration (2 microg kg(-1)), the parameters were measured again as post-fentanyl values. Thereafter, a direct laryngoscopy procedure was performed and post-laryngoscopy values for the parameters were determined. The magnitudes of response to each event were compared by using the ratio of the measurements from the preceding event. Then, comparisons of the magnitudes were performed after coordinating each response in the same direction. Our results showed that both stiffness and viscosity of mechanical impedance had greater variations than photoplethysmographic amplitude. In conclusion, we propose stiffness and viscosity derived from arterial mechanical impedance as sensitive parameters to monitor stress responses during general anesthesia.