Neurovascular mechanisms of cognitive aging: Sex-related differences in the average progression of arteriosclerosis, white matter atrophy, and cognitive decline.

Arterial stiffness (arteriosclerosis) has been linked to heightened risks for cognitive decline, and ultimately for Alzheimer's disease and other forms of dementia. Importantly, neurovascular outcomes generally vary according to one's biological sex. Here, capitalizing on a large sample of participants with neuroimaging and behavioral data (N = 203, age range = 18-87 years), we aimed to provide support for a hierarchical model of neurocognitive aging, which links age-related declines in cerebrovascular health to the rate of cognitive decline via a series of intervening variables, such as white matter integrity. By applying a novel piecewise regression approach to our cross-sectional sample to support Granger-like temporal inferences, we show that, on average, a precipitous decline in cerebral arterial elasticity (measured with diffuse optical imaging of the cerebral arterial pulse; pulse-DOT) precedes an acceleration in the development of white matter lesions by nearly a decade, with women protected from these deleterious effects until approximately age 50, the average onset of menopause. By employing multiple-mediator path analyses while controlling for sex, we show that age may impair cognition via the sequential indirect effects of arteriosclerosis and white matter atrophy on fluid, but not crystallized, abilities. Importantly, we replicate these results using pulse pressure, an independent index of arterial health, thereby providing converging evidence for the central role of arteriosclerosis as an accelerating factor in normal and pathological aging and identifying robust sex-related differences in the progression of cerebral arteriosclerosis and white matter degradation.

Association Between Arterial Pulse Waveform Analysis and Mortality in Patients With Septic Shock: A Retrospective Cohort Study Using Japanese Diagnosis Procedure Combination Data.

Purpose: Specialized pressure transducers for arterial pulse waveform analysis (S-APWA) devices are dedicated kits connected to an arterial pressure catheter that monitors hemodynamic parameters, such as cardiac output, pulse pressure variation, and stroke volume variation, less invasively. While the association between the use of S-APWA devices and clinical outcomes in perioperative patients has been previously evaluated, its assessment in patients with septic shock remains inadequate. Materials and Methods: This retrospective cohort study utilized a nationwide Diagnosis Procedure Combination database in Japan. Adult patients with septic shock admitted to the intensive care unit (ICU) with arterial pressure catheter placement on the admission day from August 2012 to February 2021 were included. Hospitalizations meeting the eligibility criteria were categorized into groups based on S-APWA device usage. The primary outcome, evaluated using Cox regression analysis, was 30-day all-cause mortality in the propensity score overlap-weighted population. Secondary outcomes included in-hospital mortality, ICU duration, and overall hospital stay. Results: Among 5130 eligible hospitalizations, 643 were in the S-APWA group and 4487 were in the conventional pressure transducer group. Cox regression analysis within the propensity score overlap-weighted population showed no significant difference in 30-day mortality (adjusted hazard ratio: 0.94; 95% confidence interval: 0.9-1.38; P = .58). Logistic regression analysis indicated no significant differences in the in-hospital mortality. While the S-APWA group had prolonged ICU stays, no significant difference in the overall hospital stay was observed according to linear regression analyses. Conclusions: Our study found no significant association between S-APWA use and 30-day mortality in patients with septic shock. These findings offer insights into optimizing monitoring systems in ICUs.

Brain-based arterial pulse pressure threshold for death determination: a systematic review.

PURPOSE: There is lack of consensus regarding the minimum arterial pulse pressure required for confirming permanent cessation of circulation for death determination by circulatory criteria in organ donors. We assessed direct and indirect evidence supporting whether one should use an arterial pulse pressure of 0 mm Hg vs more than 0 (5, 10, 20, 40) mm Hg to confirm permanent cessation of circulation. SOURCE: We conducted this systematic review as part of a larger project to develop a clinical practice guideline for death determination by circulatory or neurologic criteria. We systematically searched Ovid MEDLINE, Ovid Embase, Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Library, and Web of Science for articles published from inception until August 2021. We included all types of peer-reviewed original research publications related to arterial pulse pressure as monitored by an indwelling arterial pressure transducer around circulatory arrest or determination of death with either direct context-specific (organ donation) or indirect (outside of organ donation context) data. PRINCIPAL FINDINGS: A total of 3,289 abstracts were identified and screened for eligibility. Fourteen studies were included; three from personal libraries. Five studies were of sufficient quality for inclusion in the evidence profile for the clinical practice guideline. One study measured cessation of cortical scalp electroencephalogram (EEG) activity after withdrawal of life-sustaining measures and showed that EEG activity fell below 2 µV when the pulse pressure reached 8 mm Hg. This indirect evidence suggests there is a possibility of persistent cerebral activity at arterial pulse pressures > 5 mm Hg. CONCLUSION: Indirect evidence suggests that clinicians may incorrectly diagnose death by circulatory criteria if they apply any arterial pulse pressure threshold of greater than 5 mm Hg. Moreover, there is insufficient evidence to determine that any pulse pressure threshold greater than 0 and less than 5 can safely determine circulatory death. STUDY REGISTRATION: PROSPERO (CRD42021275763); first submitted 28 August 2021.

RéSUMé: OBJECTIF: Il n'y a pas de consensus concernant la pression artérielle minimale requise pour confirmer l'arrêt permanent de la circulation pour la détermination du décès selon des critères circulatoires chez les donneurs d'organes. Nous avons évalué les données probantes directes et indirectes soutenant l'utilisation d'une pression pulsée artérielle de 0 mmHg vs plus de 0 (5, 10, 20, 40) mm Hg pour confirmer l'arrêt définitif de la circulation. SOURCES: Nous avons réalisé cette revue systématique dans le cadre d'un projet plus vaste visant à élaborer des lignes directrices de pratique clinique pour la détermination du décès selon des critères circulatoires ou neurologiques. Nous avons mené des recherches systématiques dans Ovid MEDLINE, Ovid Embase, le registre Cochrane des études contrôlées (CENTRAL) via la Cochrane Library et Web of Science pour trouver des articles publiés depuis leur création jusqu'en août 2021. Nous avons inclus tous les types de publications de recherches originales évaluées par des pairs liées à la pression pulsée artérielle telle que surveillée par un transducteur de pression artérielle à demeure entourant un arrêt circulatoire ou de une détermination de décès avec des données directes spécifiques au contexte (don d'organes) ou indirectes (en dehors d'un contexte du don d'organes). CONSTATATIONS PRINCIPALES: Au total, 3289 résumés ont été identifiés et examinés pour déterminer leur admissibilité. Quatorze études ont été incluses, trois provenant de bibliothèques personnelles. Cinq études étaient de qualité suffisante pour être incluses dans le profil de données probantes des Lignes directrices de pratique clinique. Une étude a mesuré l'arrêt de l'activité de l'électroencéphalogramme (EEG) au niveau du scalp cortical après l'interruption des thérapies de maintien des fonctions vitales et a montré que l'activité EEG tombait en dessous de 2 µV lorsque la pression pulsée atteignait 8 mm Hg. Ces données probantes indirectes suggèrent qu'il existe une possibilité d'activité cérébrale persistante à des pressions pulsées artérielles > 5 mm Hg. CONCLUSION: Des données probantes indirectes suggèrent que les cliniciens pourraient diagnostiquer à tort un décès selon des critères circulatoires s'ils appliquent un seuil de pression pulsée artérielle supérieur à 5 mm Hg. De plus, il n'y a pas suffisamment de données probantes pour déterminer que tout seuil de pression pulsée supérieur à 0 et inférieur à 5 peut permettre de déterminer en toute sécurité un décès cardiocirculatoire. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021275763); soumis pour la première fois le 28 août 2021.

Prospective Evaluation of a Multibeat Analysis Cardiac Index Estimation in Patients With Cardiogenic Shock.

OBJECTIVES: The decision algorithm for managing patients in cardiogenic shock depends on cardiac index (CI) estimates. Cardiac index estimation via thermodilution (CI-TD) using a pulmonary artery catheter is used commonly for obtaining CI in these patients. Minimally invasive methods of estimating CI, such as multibeat analysis (CI-MBA), may be an alternative in this population. DESIGN: A prospective, observational study. SETTING: Cardiac intensive care unit. PARTICIPANTS: Twenty-two subjects in cardiogenic shock provided 101 paired CI measurements. INTERVENTIONS: Measurements were obtained concomitantly by intermittent CI-TD and CI-MBA (Argos Cardiac Output Monitor; Retia Medical, Valhalla, NY). For each CI-TD, CI-MBA estimates were averaged over 1 minute to provide paired values. Bland-Altman and 4-quadrant analyses were performed by plotting changes between successive CI measurements (ΔCI) from each of the 2 methods. Concordance was calculated as a percentage using ΔCI data points from the 2 methods, outside an exclusion zone of 15%. MEASUREMENTS AND MAIN RESULTS: The correlation coefficient between CI-MBA and CI-TD was 0.78 across patients. Mean CI-TD was 2.19 ± 0.46 L/min/m2 and mean CI-MBA was 2.38 ± 0.59 L/min/m2. The mean difference between CI-MBA and CI-TD (bias ± SD) was 0.20 ± 0.47 L/min/m2, and the limits of agreement were -0.72 to 1.11 L/min/m2. The percentage error was 40.0%. The concordance rate was 94%. A secondary analysis of a subgroup of patients during periods of arrhythmia demonstrated a similar accuracy of performance of CI-MBA. CONCLUSIONS: Cardiac index-MBA is not interchangeable with CI-TD. However, CI-MBA provides reasonable correlation and clinically acceptable trending ability compared with CI-TD. Cardiac output-MBA may be useful in trending changes in CI in patients with cardiogenic shock, especially in those whose pulmonary artery catheterization placement carries a high risk or is unobtainable.

Multimodal Finger Pulse Wave Sensing: Comparison of Forcecardiography and Photoplethysmography Sensors.

Pulse waves (PWs) are mechanical waves that propagate from the ventricles through the whole vascular system as brisk enlargements of the blood vessels' lumens, caused by sudden increases in local blood pressure. Photoplethysmography (PPG) is one of the most widespread techniques employed for PW sensing due to its ability to measure blood oxygen saturation. Other sensors and techniques have been proposed to record PWs, and include applanation tonometers, piezoelectric sensors, force sensors of different kinds, and accelerometers. The performances of these sensors have been analyzed individually, and their results have been found not to be in good agreement (e.g., in terms of PW morphology and the physiological parameters extracted). Such a comparison has led to a deeper comprehension of their strengths and weaknesses, and ultimately, to the consideration that a multimodal approach accomplished via sensor fusion would lead to a more robust, reliable, and potentially more informative methodology for PW monitoring. However, apart from various multichannel and multi-site systems proposed in the literature, no true multimodal sensors for PW recording have been proposed yet that acquire PW signals simultaneously from the same measurement site. In this study, a true multimodal PW sensor is presented, which was obtained by integrating a piezoelectric forcecardiography (FCG) sensor and a PPG sensor, thus enabling simultaneous mechanical-optical measurements of PWs from the same site on the body. The novel sensor performance was assessed by measuring the finger PWs of five healthy subjects at rest. The preliminary results of this study showed, for the first time, that a delay exists between the PWs recorded simultaneously by the PPG and FCG sensors. Despite such a delay, the pulse waveforms acquired by the PPG and FCG sensors, along with their first and second derivatives, had very high normalized cross-correlation indices in excess of 0.98. Six well-established morphological parameters of the PWs were compared via linear regression, correlation, and Bland-Altman analyses, which showed that some of these parameters were not in good agreement for all subjects. The preliminary results of this proof-of-concept study must be confirmed in a much larger cohort of subjects. Further investigation is also necessary to shed light on the physical origin of the observed delay between optical and mechanical PW signals. This research paves the way for the development of true multimodal, wearable, integrated sensors and for potential sensor fusion approaches to improve the performance of PW monitoring at various body sites.

Objective Tinnitus Secondary to Palatal Tremor: Two Case Reports.

Tinnitus is defined as a tinnitus perceived both by the patient and external observers. This category represents 1.5% of the total amount of tinnitus evaluated in tertiary healthcare institutions.

Yield of CT angiography in penetrating lower extremity trauma.

PURPOSE: CT angiography (CTA) has become a valuable tool in the assessment of suspected arterial injury in patients with penetrating lower extremity trauma. However, expensive imaging such as CTA should be judiciously utilized to ensure value-based care. We therefore assessed the yield of CTA in this setting at a level-1 trauma unit and correlated it with the clinical history provided. METHODS: A retrospective descriptive study from 1 July 2013 to 31 June 2018 at a 1386-bed, tertiary-level, public-sector teaching hospital in Cape Town, South Africa.. All patients undergoing CTA for suspected arterial injury following penetrating lower extremity trauma were included. The imaging yield of clinically significant arterial injury and the predictive value of specific clinical signs were determined. RESULTS: A total of 983 patients (median age 27 years, 91% male) were included; 90% (886/983) had gunshots, 9% (89/983) stabs, and 1% (8/983) other injuries. Despite an average 13% year-on-year increase in CTA performed, there was no change in the proportion demonstrating arterial injury. Thirty-four percent (23/68) of patients with strong (hard) signs of arterial injury (active pulsatile bleeding, rapidly expanding hematoma, absent pulse, palpable thrill, or audible bruit), 11% (49/459) with moderate (soft) signs (history of an arterial bleed, excessive non-pulsatile bleeding, large non-expanding hematoma, major neurological deficit, diminished but appreciable pulse, and arterial proximity), and 5% (24/456) with no indication for imaging had clinically significant arterial injuries. Significant positive correlations were rapidly expanding hematoma (p = 0.009), an absent pulse (p < 0.001), and a diminished pulse (p < 0.001). Significant negative correlations were proximity to a major artery (p = 0.005) and no clinical indication provided (p < 0.001). CONCLUSION: There is poor correlation between clinical details provided and the presence of arterial injury at our institution. In this context, CTA serves a pivotal role in the definitive identification of arterial injury.

Extracting new information from old waveforms: Symmetric projection attractor reconstruction: Where maths meets medicine.

NEW FINDINGS: What is the topic of this review? Symmetric Projection Attractor Reconstruction (SPAR) is a relatively new mathematical method that can extract additional information pertaining to the morphology and variability of physiological waveforms, such as arterial pulse pressure. Herein, we describe the potential utility of the method for more sensitive quantification of cardiovascular changes. What advances does it highlight? We use a simple example of a human tilt table to illustrate these concepts. SPAR can be used on any approximately periodic waveform and may add value to experimental and clinical settings, where such signals are collected routinely. ABSTRACT: Periodic physiological waveform data, such as blood pressure, pulse oximetry and ECG, are routinely sampled between 100 and 1000 Hz in preclinical research and in the clinical setting from a wide variety of implantable, bedside and wearable monitoring devices. Despite the underlying numerical waveform data being captured at such high fidelity, conventional analysis tends to reside in reporting only averages of minimum, maximum, amplitude and rate, as single point averages. Although these averages are undoubtedly of value, simplification of the data in this way means that most of the available numerical data are discarded. In turn, this may lead to subtle physiological changes being missed when investigating the cardiovascular system over time. We have developed a mathematical method (symmetric projection attractor reconstruction) that uses all the numerical data, replotting and revisualizing them in a manner that allows unique quantification of multiple changes in waveform morphology and variability. We propose that the additional quantification of these features will allow the complex behaviour of the cardiovascular system to be mapped more sensitively in different physiological and pathophysiological settings.

The association between arterial pulse waveform analysis device and in-hospital mortality in high-risk non-cardiac surgeries.

BACKGROUND: Perioperative goal-directed fluid therapy is used for haemodynamic optimization in high-risk surgeries. Cardiac output monitoring can be performed by a specialized pressure transducer for arterial pulse waveform analysis (S-APWA). No study has assessed whether real-world use of S-APWA is associated with post-operative outcomes; therefore, using a Japanese administrative claims database, we retrospectively investigated whether S-APWA use is associated with in-hospital mortality among patients undergoing high-risk surgery under general anaesthesia. METHODS: Adult patients who underwent high-risk surgery under general anaesthesia and arterial catheterization between 2014 and 2016 were divided into S-APWA and conventional arterial pressure transducer groups, then compared regarding baseline factors and outcomes. Logistic regression analysis was performed to compare in-hospital mortality. Subgroup analyses evaluated S-APWA efficacy and outcomes based on the type of surgery and patients' comorbidity. RESULTS: S-APWA was used in 6859 of 23 655 (29.0%) patients; the crude in-hospital mortality rate was 3.5%. Adjusted analysis showed no significant association between S-APWA use and in-hospital mortality rate (adjusted odds ratio [aOR] = 0.91; 95% confidence interval [CI]: 0.76-1.07; P = .25). S-APWA use was associated with significantly lower in-hospital mortality in patients undergoing vascular surgery (aOR = 0.67; 95% CI: 0.49-0.94), and significantly higher in-hospital mortality in patients undergoing lower limb amputation (aOR = 2.63; 95% CI: 1.32-5.22). S-APWA use and in-hospital mortality were not significantly associated with other subgroups. CONCLUSION: S-APWA use was not associated with in-hospital mortality in the entire study population. However, S-APWA was associated with decreased in-hospital mortality among vascular surgery and increased in-hospital mortality among lower limb amputation.

Characterization of Rat Cardiovascular System by Anacrotic/Dicrotic Notches in the Condition of Increase/Decrease of NO Bioavailability.

We characterized modes of action of NO-donor S-nitrosoglutathione (GSNO) and NO-synthase inhibitor l-NAME derived from dicrotic (DiN) and anacrotic (AnN) notches of rat arterial pulse waveform (APW) in the condition of increased/decreased NO bioavailability. The cross-relationship patterns of DiN and AnN with 34 hemodynamic parameters (HPs) induced by GSNO and l-NAME are presented. After GSNO bolus administration, approximate non-hysteresis relationships were observed in the difference between DiN-AnN (mmHg) blood pressure (BP) and other 19 HPs, suggesting that these HPs, i.e., their signaling pathways, responding to NO concentration, are directly connected. Hysteresis relationships were observed between DiN-AnN (mmHg) and other 14 HPs, suggesting that signaling pathways of these HPs are indirectly connected. The hysteresis relationships were only observed between the time interval DiN-AnN (ms) and other 34 HPs, indicating no direct connection of signaling pathways. The cross-relationship patterns of DiN-AnN (mmHg), but not DiN-AnN (ms), induced by l-NAME were in accordance to the increased NO bioavailability induced by GSNO. In conclusion, we found the non-hysteresis/hysteresis cross-relationship "patterns" of DiN-AnN intervals to other HPs in the presence of GSNO that revealed their direct or indirect signaling pathways connections. This may contribute to our understanding of biological effects of natural substances that modulate NO production and/or NO signaling pathways.

Utilization of arterial pulse waveform analysis during non-cardiac surgery in Japan: a retrospective observational study using a nationwide claims database.

Arterial pulse waveform analysis (APWA) is used for cardiac output monitoring. However, data on the frequency of and patient characteristics for specialized pressure transducer for APWA (S-APWA) use are lacking. We retrospectively identified 175,201 patients aged 18 years or older, who underwent non-cardiac surgery under general anesthesia with an arterial catheter from January 1, 2014, to December 31, 2016. We extracted data on patient demographics, comorbidities, surgical and anesthesia characteristics, and hospital characteristics. Among the full study cohort, 24,605 (14.0%) patients were monitored using S-APWA. Further, the use of S-APWA was higher in patients undergoing high-risk surgery than in those undergoing low-risk surgery [high vs low: adjusted odds ratio (aOR) 1.95; 95% confidence interval (CI) 1.76-2.15, moderate vs low: aOR 1.11; 95% CI 1.01-1.22] and those with more comorbidities than in those with less comorbidities (high vs low: aOR 1.49; 95% CI 1.42-1.56, moderate vs low: aOR 1.25; 95% CI 1.20-1.31). S-APWA use was significantly associated with both surgery risk and patients' comorbidities. In conclusion, our study may provide a benchmark for future studies related to the appropriate use of S-APWA.

Individual differences in regional cortical volumes across the life span are associated with regional optical measures of arterial elasticity.

Aging is often accompanied by changes in brain anatomy and cerebrovascular health. However, the specific relationship between declines in regional cortical volumes and loss of cerebral arterial elasticity is less clear, as only global or very localized estimates of cerebrovascular health have been available. Here we employed a novel tomographic optical method (pulse-DOT) to derive local estimates of cerebral arterial elasticity and compared regional volumetric estimates (obtained with FreeSurfer) with optical arterial elasticity estimates from the same regions in 47 healthy adults (aged 18-75). Between-subject analyses revealed a global correlation between cortical volume and cortical arterial elasticity, which was a significant mediator of the association between age and cortical volume. Crucially, a novel within-subject analysis highlighted the spatial association between regional variability in cortical volumes and arterial elasticity in the same regions. This association strengthened with age. Gains in the predictability of cortical volumes from arterial elasticity data were obtained by sharpening the resolution up to individual cortical regions. These results indicate that some of the variance of sub-clinical age-related brain atrophy is associated with differences in the status of cerebral arteries, and can help explain the unique patterns of brain atrophy found within each individual.

Goal-Directed Fluid Therapy Guided by Cardiac Monitoring During High-Risk Abdominal Surgery in Adult Patients: Cost-Effectiveness Analysis of Esophageal Doppler and Arterial Pulse Pressure Waveform Analysis.

BACKGROUND: Several minimally invasive techniques for cardiac output monitoring such as the esophageal Doppler (ED) and arterial pulse pressure waveform analysis (APPWA) have been shown to improve surgical outcomes compared with conventional clinical assessment (CCA). OBJECTIVE: To evaluate the cost-effectiveness of these techniques in high-risk abdominal surgery from the perspective of the French public health insurance fund. METHODS: An analytical decision model was constructed to compare the cost-effectiveness of ED, APPWA, and CCA. Effectiveness data were defined from meta-analyses of randomized clinical trials. The clinical end points were avoidance of hospital mortality and avoidance of major complications. Hospital costs were estimated by the cost of corresponding diagnosis-related groups. RESULTS: Both goal-directed therapy strategies evaluated were more effective and less costly than CCA. Perioperative mortality and the rate of major complications were reduced by the use of ED and APPWA. Cost reduction was mainly due to the decrease in the rate of major complications. APPWA was dominant compared with ED in 71.6% and 27.6% and dominated in 23.8% and 20.8% of the cases when the end point considered was "major complications avoided" and "death avoided," respectively. Regarding cost per death avoided, APPWA was more likely to be cost-effective than ED in a wide range of willingness to pay. CONCLUSIONS: Cardiac output monitoring during high-risk abdominal surgery is cost-effective and is associated with a reduced rate of hospital mortality and major complications, whatever the device used. The two devices evaluated had negligible costs compared with the observed reduction in hospital costs. Our comparative studies suggest a larger effect with APPWA that needs to be confirmed by further studies.

Novel theory and potential applications of central diastolic pressure decay time constant.

Central aortic diastolic pressure decay time constant ( τ ) is according to the two-element Windkessel model equal to the product of total peripheral resistance ( R ) times total arterial compliance ( C ). As such, it is related to arterial stiffness, which has considerable pathophysiological relevance in the assessment of vascular health. This study aimed to investigate the relationship of the constant τ with the product T MBP cPP , given by heart period ( T ) times the ratio of mean blood pressure (MBP) to central pulse pressure ( cPP ). The relationship was derived by performing linear fitting on an in silico population of n1 = 3818 virtual subjects, and was subsequently evaluated on in vivo data (n2 = 2263) from the large Asklepios study. The resulted expression was found to be τ = k ' T MBP cPP , with k ' = 0.7 (R2 = 0.9). The evaluation of the equation on the in vivo human data reported high agreement between the estimated and reference τ values, with a correlation coefficient equal to 0.94 and a normalized RMSE equal to 5.5%. Moreover, the analysis provided evidence that the coefficient k ' is age- and gender-independent. The proposed formula provides novel theoretical insights in the relationship between τ and central blood pressure features. In addition, it may allow for the evaluation of τ without the need for acquiring the entire central blood pressure wave, especially when an approximation of the cPP is feasible. This study adds to the current literature by contributing to the accessibility of an additional biomarker, such as the central diastolic pressure decay time constant, for the improved assessment of vascular ageing.

Peripheral artery disease diagnosis based on deep learning-enabled analysis of non-invasive arterial pulse waveforms.

This paper intends to investigate the feasibility of peripheral artery disease (PAD) diagnosis based on the analysis of non-invasive arterial pulse waveforms. We generated realistic synthetic arterial blood pressure (BP) and pulse volume recording (PVR) waveform signals pertaining to PAD present at the abdominal aorta with a wide range of severity levels using a mathematical model that simulates arterial blood circulation and arterial BP-PVR relationships. We developed a deep learning (DL)-enabled algorithm that can diagnose PAD by analyzing brachial and tibial PVR waveforms, and evaluated its efficacy in comparison with the same DL-enabled algorithm based on brachial and tibial arterial BP waveforms as well as the ankle-brachial index (ABI). The results suggested that it is possible to detect PAD based on DL-enabled PVR waveform analysis with adequate accuracy, and its detection efficacy is close to when arterial BP is used (positive and negative predictive values at 40 % abdominal aorta occlusion: 0.78 vs 0.89 and 0.85 vs 0.94; area under the ROC curve (AUC): 0.90 vs 0.97). On the other hand, its efficacy in estimating PAD severity level is not as good as when arterial BP is used (r value: 0.77 vs 0.93; Bland-Altman limits of agreement: -32%-+32 % vs -20%-+19 %). In addition, DL-enabled PVR waveform analysis significantly outperformed ABI in both detection and severity estimation. In sum, the findings from this paper suggest the potential of DL-enabled non-invasive arterial pulse waveform analysis as an affordable and non-invasive means for PAD diagnosis.

Development of a Tetherless Bioimpedance Device That Uses Morphologic Changes to Predict Blood Flow Restrictions Mimicking Peripheral Artery Disease Progression.

A tetherless multi-targeted bioimpedance device was designed, modeled, built, and tested for measuring arterial pulse and, using morphological analysis, its potential for monitoring blood flow restrictions that mimic Peripheral Artery Disease (PAD) was assessed across multiple peripheral arteries. Specifically, we first developed a small form factor, tetherless, bioimpedance device, based on high-frequency structure simulator (HFSS) simulations. After designing and building the device we then tested it in vivo on human subjects on multiple arteries and found that we did not need to modify the gain on the device compared to the bench top system. Further, it was found that changes in the morphology of the bioimpedance signal over time, depicted through the ratio of the first and second harmonic in the signal frequency, could be used to predict blood flow restrictions that mimic peripheral artery disease (PAD). The HFSS simulations helped guide the modulation frequency selection and the placement of the bioimpedance electrodes. We built the device and compared it to two commercially available bioimpedance devices and it was shown to demonstrate a distinct advantage in its multi-target capability, enabling more accurate pulse measurements from different arteries without the need for tuning the circuit for each artery. Comparing the ratio of the 1st and 2nd harmonics as a function of the blood flow restriction, the two commercial devices showed a maximum error across arteries of between 22% and 27% depending on the measurement location, whereas our system consistently displayed a stable value of just below 4%. With this system, there is the potential for comprehensive and personalized medical examinations for PAD at the point of care (POC).

Validation of a novel and existing algorithms for the estimation of pulse transit time: advancing the accuracy in pulse wave velocity measurement.

The method used for pulse transit time (PTT) estimation critically affects the accuracy and precision of regional pulse wave velocity (PWV) measurements. Several methods of PTT estimation exist, often yielding substantially different PWV values. Since there is no analytic way to determine PTT in vivo, these methods cannot be validated except by using in silico or in vitro models of known PWV and PTT values. We aimed to validate and compare the most commonly used "foot-to-foot" algorithms, namely, the " diastole-minimum," "tangential," "maximum first derivative," and "maximum second derivative" methods. Also, we propose a new "diastole-patching" method aiming to increase the accuracy and precision in PWV measurements. We simulated 2,000 cases under different hemodynamic conditions using an accurate, validated, distributed, one-dimensional arterial model. The new algorithm detects and "matches" a specific region of the pressure wave foot between the proximal and distal waveforms instead of determining characteristic points. The diastole-minimum and diastole-patching methods showed excellent agreement compared with "real" PWV values of the model, as indicated by high values of the intraclass correlation coefficient (>0.86). The diastole-patching method resulted in low bias (absolute mean difference: 0.26 m/s). In contrast, PWV estimated by the maximum first derivative, maximum second derivative, and tangentia methods presented low to moderate agreement and poor accuracy (intraclass correlation coefficient: <0.79 and bias: >0.9 m/s). The diastole-patching method yielded PWV measurements with the highest agreement, accuracy, and precision and lowest variability.

Harmonic effects of sham acupuncture at Tsu San Li (St-36) in the radial pulse wave.

Background and aim: Acupuncture has been criticized as a theatrical placebo for the sham effect. Unfortunately, sham tests used in control groups in acupuncture studies have always ignored the underlying biophysical factors, including resonance involved in acupuncture points and meridians. Experimental procedure: In this study, the effects of sham acupuncture at Tsu San Li (St-36) were examined by analyzing noninvasive 30-sec. recordings of the radial arterial pulses for 3 groups of patients treated with different probes (blunt, sharp, and patch) on the superficial skin of the acupuncture point. The 3 groups were then treated with the sharp probe for 3 different periods (16, 30, and 50 s). Then we compared the harmonics of the radial arterial pulse after Fourier transformation before and after the treatment. Results: Our results indicated that different probes have effects similar to needle insertion at Tsu San Li. Meanwhile, the harmonic effect of the sharp probe strengthened as time increased. Conclusions: This study revealed that the meridian effect of sham testing from mechanical stimulation, even from simple touch, on an acupuncture point, should not be overlooked. Thus, even simple touch can be added to electrical or laser acupuncture.

Use of a rat model to characterize 35 arterial pulse wave parameters in a comparative study of isoflurane and Zoletil/xylazine anesthesia and the effect of Acanthopanax senticosus extract.

BACKGROUND: Information obtained from arterial pulse waveforms (APW) can be useful for characterizing the cardiovascular system. To achieve this, it is necessary to know the detailed characteristics of APWs in different states of an organism, which would allow APW parameters (APW-Ps) to be assigned to particular (patho)physiological conditions. Therefore, our work aimed to characterize 35 APW-Ps in rats under the influence of isoflurane (ISO) and Zoletil/xylazine (ZO/XY) anesthesia and to study the effect of root extract from Acanthopanax senticosus (ASRE) in these anesthetic conditions. METHODS: The right jugular vein of anesthetized rats was cannulated for the administration of ASRE and the left carotid artery for the detection of APWs from which 35 APW-Ps were evaluated. RESULTS: We obtained data on 35 APW-Ps, which significantly depended on the anesthesia, and thus, they characterized the cardiovascular system under these two conditions. ASRE transiently modulated all 35 APW-Ps, including a transient decrease in systolic and diastolic blood pressure (BP) and heart rate or increases in pulse BP, dP/dtmax , and systolic and diastolic areas. Whereas the transient effects of ASRE were similar, the extract had prolonged disturbing effects on the cardiovascular system in rats under ZO/XY but not under ISO anesthesia. This negative effect can result from the disturbance caused by ZO/XY anesthesia on the cardiovascular system. CONCLUSIONS: We characterized 35 APW-Ps of rats under ISO and ZO/XY anesthesia and found that ASRE contains compounds that can modulate the properties of the cardiovascular system, which significantly depended on the status of the cardiovascular system. This should be considered when using ASRE as a nutritional supplement by individuals with cardiovascular problems.