The study focused on the application value of iteration reconstruction algorithm-based ultrasound and spiral computed tomography (CT) examinations, and the safety of dexmedetomidine anesthesia in acute abdominal surgery.  80 cases having the acute abdomen surgery were selected as the research subjects. They were divided into group A (40 cases) and group B (40 cases) according to the anesthetic drugs used in the later period. The experimental group was injected with propofol, remifentanil, and atracurium combined with dexmedetomidine; the control group was injected with propofol, remifentanil, and atracurium only. After the operation, the patient was for observed for the pain, agitation, adverse reactions, heart rate (HR), and blood pressure. All patients received ultrasound and spiral CT examinations, and based on the characteristics of the back-projection algorithm, an accelerated algorithm was established and used to process the image, and according to which, the patient's condition and curative effects were evaluated. P < 0.05). The Ramsay score of the experimental group was significantly higher than that of the control group at each time period, P < 0.05; the agitation score and visual analogue scale (VAS) score of the experimental group were significantly lower than the control group at each time period after waking up, P < 0.05.  After image reconstruction, the ultrasound and spiral CT images were clearer with less noise and more prominent lesions than before reconstruction. Before image reconstruction, the accuracy rates of ultrasound and spiral CT in diagnosing acute abdomen were 92.3% and 91.1%, respectively. After reconstruction, the corresponding numbers were 96.3% and 98.1%, respectively. After reconstruction, the accuracy of the two methods in diagnosing acute abdomen was significantly improved compared with that before reconstruction, and the difference was statistically significant ( Reconstruction algorithm-based ultrasound and spiral CT images have high application value in the diagnosis of patients with acute abdomen, and dexmedetomidine has good safety in anesthesia surgery. It can act on α2 receptors in the central nervous system, peripheral nervous system, and other tissues to produce analgesic, sedative, and antisympathetic effects. Unlike commonly used opioids, it does not cause pain and allergies in animals, and there is no abnormal pain after drug withdrawal. When combined with alfentanil, it can enhance its analgesic effect and will not aggravate respiratory depression [Acute abdomen is a common disease in clinic, divided into traumatic and nontraumatic ones. It is a general term for diseases mainly manifesting as acute pain in different parts of the abdomen. It has the characteristics of rapid onset, rapid progress, and many changes. A good prognosis requires timely treatment . Otherwipression . NonetheRecently, with the rapid development of physical technology and modern computer technology, ultrasound and spiral CT technology have also developed rapidly. Ultrasonic acquisition equipment has developed from mechanical scanning to electronic scanning and from one-dimensional probes to two-dimensional array probes. However, a large amount of ultrasound data obtained cannot be used . In thisIn this study, an artificial intelligence algorithm was used to reconstruct the ultrasound and spiral CT images of patients undergoing the acute abdominal surgery, and on this basis, the efficacy and safety of dexmedetomidine in anesthesia for acute abdominal surgery were explored expected to provide a reference for clinical diagnosis and treatment of related diseases.A total of 80 patients having the acute abdomen surgery from April 2019 to August 2020 were selected as the research subjects, including 44 male patients and 36 female patients, with an average age of the patients which was 55.7 ± 11.7 years. The patients were randomly divided into group A (40 cases) and group B (40 cases). The experimental group was injected with propofol (4~6 mg/kg), remifentanil (0.15~0.2 mg/kg), and atracurium combined (0.1~0.15 mg/kg) with dexmedetomidine; the control group was injected with propofol (4~6 mg/kg), remifentanil (0.15~0.2 mg/kg), and atracurium alone (0.1~0.15 mg/kg). Inclusion criteria are as follows: patients with acute abdomen, patients who are not allergic to the drugs used in the experiment, voluntary to participate in the experiment, and there is no mental or cognitive disease. Exclusion criteria are as follows: people suffering from hypertension, people suffering from more serious underlying diseases such as coronary heart disease, people with liver and kidney dysfunction, people allergic to the study drug, and people who cannot communicate normally. All patients in this article signed the informed consent form, and the experiment was approved by the ethics committee of the hospital.The Doppler color ultrasound diagnostic apparatus EUB5500 was used, to perform abdominal and pelvic ultrasound examination of the patient, with a probe frequency of 3.5~7 MHz. The patient generally took a supine, lateral, or prone position. Patients with trauma were scanned for the celiac fissure, especially the injured site. During the examination, attention should be paid to avoid moving as much as possible so that the injury would not be aggravated; patients without trauma were examined according to the requirements of the emergency doctor, and if necessary, a comprehensive scan should be performed. After the lesion was found, its location and ultrasound performance were recorded immediately.The axial plain scan was performed by 16-slice spiral CT examination, and the scan range was from septum to pubic symphysis; for patients suspected of arteriovenous thrombosis and gastrointestinal hemorrhage, an enhanced scan was added using the nonionic contrast agent, 90-100 mL each time. It was injected using a high-pressure booster at 2.5 mL/s. After the scan was completed, the physician carefully observed and analyzed the condition of the disease and then issued a diagnosis report. β − ϕ) can be simplified according to Equations ..β − ϕ) cβ and ϕ ranges from 0 and 360 degrees. The reconstruction area is divided into four quadrants, and the projection data is also divided into four areas according to the projection angle, 0 < β1 ≤ 90, 90 < β2 ≤ 180, 180 < β3 ≤ 270, 270 < β4 ≤ 360. Four points A, B, C, D are taken during the reconstruction. These four points belong to the four quadrants, with equal values of r, and the values of λ differ by 90° in sequence, as shown in The value of (1)E in the first quadrant, when 0 < β1 ≤ 90, rsin(β1 − ϕ), and rcos(β1 − ϕ) are calculated, and then U and s′ are calculated according to Equations (For the points quations  and 3)::E (2)β2 = β1 + 90, the values of r are equal. Relative to point E1, there isWhen The reconstruction steps are as follows. E in the first quadrant, there is only one point corresponding to each in the second quadrant, and the U and s′ values of one point correspond to those of the other. And so on, for β2 = β1 + 180, the U and s′ of the point E2 are equal to the point E. For β4 = β1 + 270, the U and s′ of point E3 are equal to point E. Therefore, for the points U and s′ only once, reducing the calculation time. β1 ≤ 90, the U and s′ corresponding to the E1 in the second quadrant are calculated.(3) When 0 < Hence, the values of four points can be obtained by calculating rsin(β1 − ϕ) and rcos(β1 − ϕ) have been calculated in step 1, so this step only needs to calculate the floating point. U and s′ corresponding to E2 and E3 can be calculated.In a similar way, the values of 2), partial pressure of end-tidal carbon dioxide (PETCO2), and bispectral index (BIS) were routinely monitored. Radial artery puncture and catheterization were performed under local anesthesia to monitor the arterial blood pressure (ABP). Each patient was injected with 0.06 mg/kg of midazolam, 0.4 μg/kg of sufentanil, 0.3 mg/kg of etomidate, and 0.9 mg/kg of rocuronium after 5 minutes of mask ventilation and preoxygenation. Endotracheal intubation was performed when the patient was unconscious and when spontaneous breathing disappeared. After successful intubation, the anesthesia machine was connected for intermittent positive pressure ventilation, the breathing rate was set to 12-15 times/min, the tidal volume was set to 8-10 mL/kg, the inspiratory-expiratory ratio was set to 1 : 2, and the fresh oxygen was inhaled at 2 L/min. The ventilator parameters were adjusted according to the intraoperative arterial blood gas condition, and PETCO2 was maintained at 35~45 mmHg. Puncture and catheterization of internal jugular vein or subclavian vein were performed to open the central vein to monitor central venous pressure (CVP). During the operation, propofol of 4~6 mg/kg, remifentanil of 0.15~0.2 μg/kg/min, and cis-atracurium of 0.1~0.15 mg/kg/h were continuously injected to maintain the depth of anesthesia and muscle relaxation. During the operation, sevoflurane was inhaled according to the BIS value. Sevoflurane was stopped 30 minutes before the end of the operation. The experimental group was given 0.5 μg/kg dexmedetomidine intravenously 30 minutes before the end of the operation, which should be finished within 20 minutes; the control group was given 5 mL of normal saline intravenously 30 minutes before the end of the operation.In the operating room, the peripheral vein was open, and electrocardiogram (ECG), heart rate (HR), oxygen saturation (SpO2 were recorded at five points of before drug administration (T0), before extubation (T1), immediately after extubation (T2), 5 min after extubation (T3), 10 min after extubation (T4), and during postanesthesia care unit (PACU) (T5). (2) The recovery time of spontaneous breathing, eye-opening time, extubation time, and PACU time were observed. (3) The visual analogue scale (VAS) score, Ramsay score, and agitation score at T2~T5 were calculated. (4) The concentration of blood glucose, SP, cortisol, epinephrine, and norepinephrine in central venous blood was detected at T0, T3, and T5. (5) Other adverse reactions(1) Mean arterial pressure (MAP), HR, and SpOVAS scoring standard is as follows: 0 points, no pain; 1~3 points, slight pain, tolerable; 4~6 points, the pain affects sleep, but is still tolerable; and 7~10 points, severe pain, intolerable.Ramsay scoring standard is as follows: 1 point, awake: the patient is anxious, restless, or irritable; 2 points, awake: the patient has good orientation or is quiet; 3 points, awake: the patient only responds to commands; 4 points, sleep: the patient responds quickly to slight touch to the area between eyebrows or strong sound stimulation; 5 points, sleep: the patient responds slowly to light tapping of the eyebrows or strong sound stimulation; 6 points, sleep: the patient has no response to light tapping of the eyebrows or strong sound stimulation.Agitation score is as follows: 0 points, quiet and cooperative; 1 point, physical activity during sputum suction stimulation; 2 points, struggle when there is no stimulation, but no need to press; 3 points, struggling violently, pressing is required.t-test, comparison within groups was performed by analysis of variance, count data adopted the χ2 test, and P < 0.05 indicated that the difference was statistically significant.SPSS 22.0 statistical software was used for data analysis, measurement data was expressed as the mean ± standard deviation .P < 0.05.P < 0.05.P < 0.05.Acute abdomen is a common disease with rapid onset and rapid progress. If not diagnosed and treated in time, it will endanger the health and life of the patient. At present, the imaging examination is commonly used for the diagnosis of acute abdomen , includiAn important aspect of the innovation of ultrasound and spiral CT is image processing technology. With the continuous advancement of computer and Internet technology, image processing technology has developed rapidly, playing an increasingly important role in many fields . At the For the treatment of acute abdomen, the surgery treatment method is mainly used. Together, general anesthesia is mostly used during surgery. Propofol and remifentanil are commonly used anesthesia and analgesia methods, but there are many problems . Plus, vP < 0.05). Ramsay sedation scores at T2, T3, T4, and T5 in group A were 2.89 ± 0.38, 2.41 ± 0.44, 2.31 ± 0.48, and 2.11 ± 0, respectively, and Ramsay sedation scores at T2, T3, T4, and T5 in group B were 1 ± 0, 2 ± 0, 1.77 ± 0.489, and 1.88 ± 0.37, respectively. Ramsay sedation scores in group A were significantly higher than that of group B at each time point after awakening, with statistical significance (P < 0.05). This indicated that dexmedetomidine had good performance and safety in postoperative anesthesia for acute abdomen. Previous studies in related fields were all conducted on a single aspect, and there were few studies that integrated algorithm, acute abdomen, and anesthetic effect of dexmedetomidine. Thus, this study provides a reference for clinical diagnosis and treatment of acute abdomen.In this article, the existing imaging processing algorithm was optimized first and then used to process the image. The study found that the processed ultrasound and spiral CT images were clearer, of better quality, and more accurate in the diagnosis of acute abdomen. At the same time, the efficacy and safety of dexmedetomidine in anesthesia for acute abdomen surgery were evaluated. The results showed that the VAS scores of T2, T3, T4, and T5 in group A were 3.9 ± 1.11, 3.7 ± 1.31, 3.11 ± 0.93, and 3.28 ± 0.88, respectively, and that the VAS scores of T2, T3, T4, and T5 in group B were 5.77 ± 1.33, 5.2 ± 1.48, 4.9 ± 1.53, and 4.68 ± 1.55, respectively. The VAS scores at T2, T3, T4, and T5 in group A were significantly lower than group B, with statistical significance (In this article, the existing image processing algorithm was optimized first and then used to process the ultrasound and spiral CT images. The study found that the processed ultrasound and spiral CT images were clearer and better in quality, and the accuracy of the diagnosis of acute abdomen was higher. At the same time, the efficacy and safety of dexmedetomidine in anesthesia for acute abdomen surgery were evaluated. Moreover, compared with the control group, the experimental group had significantly better indicators, indicating better anesthesia performance and safety. This study provides a reference for the diagnosis and treatment of acute abdomen. However, some limitations in the study should be noted. The sample size is small, which will reduce the power of the study. In the follow-up, an expanded sample size is necessary to strengthen the findings of the study.


Background: Patients after myocardial infarction have impaired vascular function. However, effects of lifestyle, e.g., physical activity level, on endothelial function and arterial stiffness remain scarce. The aim of our study was to investigate effects of physical activity level and risk factors on endothelial function and arterial stiffness.Methods: In this cross-sectional study, we ultrasonographically assessed parameters of vascular function, namely flow mediated dilation (FMD) of the brachial artery and carotid artery stiffness in patients after myocardial infarction referred to the cardiac rehabilitation. The International Physical Activity Questionnaire (IPAQ) was obtained from all participants. Based on the IPAQ, patients were classified into three groups: vigorous, moderate, and low physical activity engagement. ANOVA was used for comparison among three groups using Bonferroni correction to determine differences between two sub-groups.Results: One hundred and eight patients after myocardial infarction (mean age 53 ± 10 years) were included. There were significant differences in terms of FMD  and pulse wave velocity (PWV), a measure of arterial stiffness  among groups of vigorous, moderate, and low physical activity engagement, respectively. However, in younger patients only FMD remained associated with physical activity level, while arterial stiffness was not. Low physical activity engagement was a significant predictor of both FMD and PWV in univariate and multivariate models, adjusted for age, sex, and other risk factors.Conclusion: Low physical activity level is associated with impaired endothelial function and increased arterial stiffness in patients after myocardial infarction. Future studies are warranted to address this issue in a context of cardiac rehabilitation protocols optimization in order to improve vascular function in these patients. Myocardial infarction is a terminal step in the atherosclerotic pathophysiology. It starts with the functional impairment  and leadHowever, certain lifestyle changes can modify vascular function. Physical activity is recommended by the relevant guidelines for healthy individuals, various conditions including cardiovascular patients , as it iIn the present study, we thought to compare vascular function  in terms of physical activity level, in patients after myocardial infarction. Additionally, our aim was to check if there are differences in these associations in younger and older patients.Patients older than 18 years of age, who suffered myocardial infarction in the period less than 4 months, were screened for the study before commencement of the outpatient clinic cardiac rehabilitation program at the Centre for Preventive Cardiology, Department of Vascular Diseases, University Medical Centre Ljubljana, Slovenia. Exclusion criteria included acute illness 1 month prior to inclusion, non-cardiovascular diseases (CVDs) decompensation requiring hospital admission, emergency or unplanned specialist management, unstable dysrhythmias, pregnancy, and intellectual development disorder. The study was approved by the National Medical Ethics Committee and has been performed in accordance with the Declaration of Helsinki and its later amendments. Written consent was obtained from all patients prior to their inclusion.Patients’ clinical data was analyzed, vascular function, and cardiopulmonary exercise testing were performed.Maximal cardiopulmonary exercise testing (CPET) was performed using cycle ergometer Schiller CS-200. CPET protocol consisted of initial 3-min interval without workload, which was followed by gradual increase in workload every minute by one tenth of maximal estimated workload, calculated based on age, gender, and height.The flow of oxygen and carbon dioxide during exercise was monitored with a mouthpiece connected to the device, ECG and heart rate (HR) were monitored continuously during and immediately after the CPET and blood pressure was measured manually every 2 min. Patients gave their maximal effort before they stopped cycling. Testing was discontinued at the onset of symptoms , signs , and/or ischemic changes in the electrocardiographic record or occurrence of arrhythmias.2peak), resting and peak heart rate, resting and peak systolic and diastolic blood pressure, and peak systolic pressure times peak heart rate.Data obtained from the CPET were, as follows: peak oxygen uptake , using Aloka ProSound α7 ultrasound device and a 10 MHz linear array transducer. The probe was positioned with a dedicated mechanical support. If this was not possible, we performed the measurements manually. The evaluations were made by two skilled observers with previous data on intra- and interobserver variability for FMD and pulse wave velocity (PWV) measurements. For this study, we have performed additional intra- and inter-observer reliability appraisal. For FMD, intra- and inter-rater reliability coefficients were 0.906 and 0.821, respectively and for PWV, intra- and inter-rater reliability coefficients were 0.976 and 0.969, respectively. Firstly, the right brachial artery was scanned in the longitudinal section approximately 5 cm above the antecubital fossa to find the clearest image of the anterior and posterior arterial wall layer. The first image was then obtained. Secondly, to increase hyperemic flow, the cuff was placed and inflated on the middle third of the forearm to a pressure of 50 mmHg above the patient’s systolic pressure for 4.5 min. About 60 s after cuff deflation, the second image was obtained. At the post processing, at least three measurements of the arterial diameter were obtained, and the average value of measurements was determined at baseline (d1) and 60 s after the cuff deflation (d2). FMD was expressed as a percentage change of the diameter after reactive hyperemia relative to the baseline scan using the following formula: (d2-d1)/d1 and expressed in percentage.The endothelium-independent vasodilation test was not performed due to the logistic reasons. The endothelium-independent dilation test is performed using the nitroglycerin. As nitroglycerin is known to affect exercise performance, we decided not to perform it as participants underwent cardiopulmonary exercise testing or had the first cardiac rehabilitation session just after the ultrasound examination.Arterial stiffness was determined by measuring the parameters of carotid arterial stiffness, e.g., β stiffness coefficient and PWV. The measurements were performed using Aloka ProSound α7 ultrasound device, with echo tracking software to determine carotid stiffness parameters through the analysis of the pulse waves, and a 10 MHz linear array transducer. Patients rested in the supine position for 10 min before hemodynamic measurements. Blood pressure was measured on the left upper extremity and arterial stiffness measurements were performed on the right common carotid artery (RCCA). Patients had their head elevated at around 45° and tilted to the left by 30°.We initially scanned the RCCA about 2 cm before the carotid bifurcation. Then the cursor pair was positioned on the anterior and posterior walls of the RCCA artery. The dedicated program then analyzed the waveform signals caused by periodic changes in the diameter of the common carotid artery based on the systolic and diastolic pressures and automatically determined the stiffness coefficient β and PWV. Calibration of the blood pressure was performed twice and for each we performed six consecutive measurements. The stiffness coefficient β and PWV were determined as average value of 12 measurements .In order to determine physical activity level before myocardial infarction, the International Physical Activity Questionnaire (IPAQ) was determined twice within 2 weeks in order to prevent possible overestimation and obtain reliable physical activity level. According to the authors’ guidelines, physical activity level was classified into three levels, as follows: vigorous, moderate, and low physical activity level .t-test and Mann-Whitney U tests were performed for comparison of two groups for normally and asymmetrically distributed variables, respectively. Univariate and multivariate linear regression analyses were performed to determine predictors of the vascular function parameters. Chi square test was used to assess differences of categorical variables. Data were analyzed with the IBM SPSS Statistics v. 20. A value of p < 0.05 was considered statistically significant.The normal distribution of variables was assessed with the Kolmogorov-Smirnov test after previous graphical description. Normally distributed continuous variables were expressed as mean values and SDs, while asymmetrically distributed continuous variables were expressed as median and interquartile ranges. Categorical variables were expressed as numbers and percentages. ANOVA with Bonferroni adjustment, and Kruskal-Wallis test were used for comparison of three groups for normally and asymmetrically distributed variables, respectively. Independent samples p = 0.004) and FMD  among vigorous, moderate, and low physical activity level group, respectively. Also, differences were significant among groups in terms of exercise capacity  were females, average age was 55.4 years . Median p = 0.353 and 7.8 vs. 8.0 vs. 8.6, p = 0.657, respectively). However, there were significant differences in terms of FMD . Conversely, in older half of patients (≥55 years of age), differences in terms of both arterial stiffness parameters and FMD were significant  on endothelial function in healthy populations and various cardiovascular conditions . More viAnother intriguing result of our study are discrepancies between associations of physical activity level and arterial stiffness in different age groups. According to our results, only in older patients after myocardial infarction, arterial stiffness is associated with physical activity level, while in younger it does not, which is in line with results of Tobacco smoking contributes greatly to initiation of atherogenesis and consequent early myocardial infarction . The mosMean arterial pressure was shown to be another significant predictor of the arterial stiffness. This significant association provides a key understanding of the arterial elasticity and consequences of the arterial wall with changes in arterial pressure. Higher blood pressure decreases arterial extensibility mostly through the engagement of the collagen fibers in the media, which are dependent of higher blood pressure, so the wall becomes stiffer, thus quicker conducting pulse waves. On the contrary, lower blood pressure mostly engages elastin component of the arterial media, providing arterial distensibility . AlthougDyslipidaemia as a risk factor emerged as a significant factor of endothelial dysfunction . As alreThere are some limitations of our study. Firstly, a sample size and a single-center setting. Although our sample size was relatively large in comparison to previous reports, its single-center pattern may decrease generalizability to other populations. Therefore, larger multi-center studies are needed to confirm our results. Secondly, this is a cross-sectional study and can only answer the question of association, not causality. Thirdly, physical activity level was assessed using the IPAQ questionnaire and not with the modern electronic analyzers of physical activity. Nevertheless, in our study IPAQ questionnaire classification correlated well with CPET results, which is in line with some literature reports on coronary artery disease patients  and otheTo conclude, physical activity level is associated with endothelial function in patients after myocardial infarction. Additionally, there is a significant association between physical activity level and arterial stiffness, but only in older patients after myocardial infarction.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by National Medical Ethics Committee of the Republic of Slovenia. The patients/participants provided their written informed consent to participate in this study.JT contributed to drafting the work, acquisition, analysis, and interpretation of the data for the work, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. DK contributed to data acquisition, analysis, and interpretation, and drafting the work. UR organized the database and contributed to the data analysis and interpretation. ZF substantially contributed to the data analysis and interpretation, and manuscript revision. BJ and MN contributed to conception and design of the study, drafting the work, revising it critically for important intellectual content, and provided approval for the final manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The prevalence of neuropathic lesions in young patients with type 1 diabetes mellitus (T1DM) at the time of transition from pediatric care to adult-oriented diabetes care is poorly studied. A comparative study with healthy volunteers to assess the possible neuropathic condition of this special population and to identify the potential early screening needs has not been performed yet. The results may provide important feedback to pediatric diabetes care and a remarkable baseline reference point for further follow up in adult diabetes care.®, Neuropad®-test, Tiptherm®, Monofilament®, and Rydel-Seiffer tuning fork tests.Twenty-nine young patients with T1DM  and 30 healthy volunteers  were involved in the study. Autonomic function was assessed by standard cardiovascular reflex tests. Complex peripheral neuropathic testing was performed by Neurometervs. 74 ± 8 mmHg, p < 0.01), but there was no significant difference in systolic blood pressure (127 ± 26 vs. 121 ± 13 mmHg). Cardiovascular reflex tests had not revealed any significant differences between the T1DM patients and controls. No significant differences with Neurometer®, Neuropad®-test, and Monofilament® were detected between the two groups. The vibrational sensing on the radius on both sides was significantly impaired in the T1DM group compared to the controls with Rydel-Seiffer tuning fork test . The Tiptherm®-test also identified a significant impairment in T1DM patients . In addition, the neuropathic complaints were significantly more frequently present in the T1DM patient group than in the controls .T1DM patients had significantly higher diastolic blood pressure than controls (80 ± 9 ®-tests revealed peripheral sensory neurological impairments in young T1DM patients at the time of their transition to adult diabetes care.In this young T1DM population, cardiovascular autonomic neuropathy and cardiac morphological alterations could not be found. However, Rydel-Seiffer tuning fork and Tiptherm Diabetes mellitus is one of the most common chronic diseases in children and adolescents , 2, and The prevalence of cardiovascular autonomic neuropathy (CAN) was at least 20% in unselected type 1 and type 2 diabetic patients –10 and vClinical diabetic neuropathy is rarely seen in pediatric populations; however, subclinical neuropathy  may be common among adolescents –20. In dHealth care transition (HCT) is a prepared, systematic process to transfer adolescents and young adults with chronic diseases from pediatric to adult health care systems , 33; nevYoung patients with type 1 diabetes mellitus were eligible for the study at the time of health care transition from the Department of Pediatrics and Pediatric Health Center to the Department of Medicine at the University of Szeged, Hungary. The measurements were performed from September 2019 to February 2020 as the first neuropathic status assessment in adult care. The exclusion criteria included cases of pernicious anemia, alcoholism, chronic hepatitis, uremia, exposure to chemical agents, nerve compression, and chemotherapy treatment.2; hemoglobin A1c (HbA1c): 8.5 ± 2.1%, mean diabetes duration: 12.2 ± 5.8 years; 13 men/16 women; (mean ± SD)]. A total of 30 age-matched healthy volunteers  were enrolled in the study as controls.We studied 29 young patients with T1DM [age: 22.4 ± 2.9 years; body mass index (BMI): 22.8 ± 3.0 kg/mStandard cardiovascular reflex tests were applied  to charaThree of these reflex tests record the changes of heart rate during specific maneuvers: during deep breathing (HRRDB), in positions of lying then standing up (30/15 ratio), and during and after a Valsalva maneuver , while one test was designed to evaluate systolic blood pressure changes from lying to standing up (SBPRSU) . Those tNormally, the heart rate is increased during inspiration and decreased by expiration. The patient was asked to breathe deeply at the rate of six breaths per minute (5 s in and 5 s out). The result was expressed as the difference between the measured maximum and minimum heart rates (beats/min) during the six breathing cycles.th beat after standing up. Then, a relative bradycardia occurs in healthy subjects with the lowest heart rate at about the 30th heartbeat. At the start of the test, the patient was in the supine position while the electrocardiogram was recorded continuously. Then the patient stood up without interrupting the recording. The 30/15 ratio was expressed as the ratio of the longest R-R interval (at around the 30th beat) to the shortest R-R interval (at around the 15th beat) following standing up.Following the position change from lying to standing up, the heart rate is immediately increased and reaches its maximum at around the 15During the strain period of Valsalva maneuver, the blood pressure drops and the heart rate rises under physiologic conditions. Following the procedure, the blood pressure rises and the heart rate slows. The patient was instructed to blow into a mouthpiece connected to a modified manometer and holding it at a pressure of 40 mmHg for 15 s, while an electrocardiogram was recorded continuously. The Valsalva ratio was calculated as the ratio of the longest R-R interval after the maneuver to the shortest R-R interval during the procedure.st, 5th, and 10th minutes after standing up. The largest difference from the systolic pressure in lying is evaluated as the blood pressure response to standing.In healthy standing subjects, the pooling of blood in the lower extremities is rapidly corrected by peripheral vasoconstriction. Severe postural hypotension is a characteristic sign of CAN. This test is based on blood pressure measurements in lying position and following standing up. The postural fall in blood pressure is defined as the difference between systolic blood pressure after 10 min in the supine position and systolic blood pressures at the 1® . This device is suitable for the quantification of the function of different nerve fibers and provides a simple, non-invasive, and quantitative measure of peripheral sensory function  is a pen-shaped device with two flat sides used for early diagnosis of symmetrical polyneuropathy, which measures temperature sensitivity of the skin (®. Candidates with disturbed temperature sensation (≥10°C) are unable to recognize the difference.The Tipthermthe skin . This dethe skin . CandidaNeuropathic complaints were assessed by a questionnaire. Every individual had to make a statement about the presence or absence of burning, pinprick sensation, numbness, tingling, hypoesthesia, hyperesthesia, and also about the intensity of these symptoms and frequency of their occurrence.Fasting venous blood and urine samples were obtained from patients and controls for the determination of glucose, hemoglobin A1c, blood urea nitrogen, corrected calcium, magnesium, sodium, potassium, total protein, albumin, alkaline phosphatase, urine pH, and for complete lipid, liver, and blood test profiles. Due to logistical reasons, the collection of the blood and urine samples was not possible from all patients and controls.Transthoracic echocardiography has been performed to determine standard morphological and functional parameters. The subjects underwent a complete two-dimensional (2D) transthoracic echocardiographic study using a Toshiba Artida imaging system  with a PST-30SBP phased-array transducer (1–5 MHz). The images were obtained in accordance with the recommendations of the American Society of Echocardiography and the European Association of Cardiovascular Imaging . In all https://www.r-project.org/), and values of p < 0.05 were considered significant.Statistical data were reported as the mean ± SD, with frequencies (n) and percentages (%), when appropriate. Power analysis for the study was performed using the software G* Power (Version 3.1.9.2) for power-and-sample size calculation . The calculated sample size was 28, working with an effect size d = 0.8, alpha as Type I error of 0.05, and a power value of 0.95. Pearson’s chi-squared test or Fisher’s exact test was used to analyze categorical data, whereas independent samples t-test was used in case of continuous data. Statistical tests were performed using R statistical software  of the World Medical Association and was approved by the Hungarian Medical Research Council . All subjects have given written informed consent of the study.vs. 74 ± 8 mmHg; p = 0.003; 2+ channel blockers).Relevant clinical data of T1DM patients and control subjects are presented in Regarding the laboratory parameters, average serum glucose and HbA1c values were significantly higher in young patients with type 1 DM compared to healthy controls (Standard cardiovascular reflex tests did not indicate any significant deteriorations in the heart rate responses to deep breathing (HRRDB), to standing up (30/15 ratio), and to Valsalva maneuver  or in the systolic blood pressure response from lying to standing up (SBPRSU) in young T1DM subjects compared to controls. Autonomic parameters of young T1DM patients and age-matched control subjects are shown in ® . In addition, the neuropathic complaints were significantly more frequently present in the T1DM patient group than in the controls .No significant differences were detected with NeurometerDiabetes duration (12.2 ± 5.8 years) did not correlate with the results of the cardiovascular reflex tests , the HbA1c level , or the diastolic blood pressure in T1DM patients . In addition, no correlation was found between DM duration and the results of the vibration testing by Rydel-Seiffer graduated tuning fork on the right  and left  radius.®-tests and the HbA1c level .In the whole observed population (diabetic and control subjects together), a significant correlation was found between the HbA1c level and the Valsalva ratio  and diastolic blood pressure . Furthermore, a borderline relationship was found between the results of the Tiptherm®-test, along with more severe neuropathic complaints in the T1DM patient group than in the controls.In this young T1DM population, at the time of transition from pediatric care to adult-oriented health care system, cardiovascular autonomic neuropathy or cardiac morphological disorders were not found. However, besides intact cardiovascular autonomic and cardiac conditions, peripheral sensory neurological impairments were detected with the 128 Hz Rydel-Seiffer graduated tuning fork test and the TipthermAs poor glycemic control is the most important risk factor for the development of diabetic peripheral neuropathy (DPN) , 50, 51,per se is not surprising as the large-fiber dysfunction appears first in diabetic length-dependent peripheral neuropathy. However, peripheral neuropathies may affect different types of nerve fibers to different degrees, and the usual concept is that sensory nerves in the lower limb are predominantly affected and symptoms begin at the terminal of the longest nerves in diabetes mellitus  Clinical Practice Consensus Guidelines released in 2018, the screening for peripheral neuropathy should start from age 11 years with 2 to 5 years of diabetes duration and it should be performed annually thereafter . Assessmmellitus . On the mellitus , 56.The majority of studies on diabetes consider peripheral sensorimotor neuropathy of the lower extremities, and only a few, mostly sensory and motor nerve conduction velocity studies have examined sensory function in the hands –61.The examination of the vibration perception can be useful to detect diabetic peripheral sensory neuropathy at an early stage, and it can be easily assessed by a 128 Hz tuning fork . NormatiDue to the relative paucity of data on this issue, and given the unusual nature of our present findings on reduced vibration sensation in the upper but not in the lower limbs in young T1DM patients, further studies are warranted to confirm and/or extend these results.According to recent guidelines , 66, it Two risk factors are common in both T1DM and T2DM: the lack of proper glycemic control and the duration of diabetes; however, the most characteristic difference regarding CAN in T1DM and T2DM is the fact that the signs and symptoms appear later in T1DM than in T2DM. This is likely due to the longer duration of the metabolic abnormalities (dysglycemia) and the cascade of multiple complex mechanisms and pathogenic pathways that induce oxidative stress and autonomic neuronal dysfunction in diabetes, which occur already prior to the diagnosis of T2DM –72. The Among the young T1DM patients, we found significantly higher comorbidity with hypertension (in six diabetic patients) with a significantly increased diastolic blood pressure without detectable cardiac morphologic differences or cardiovascular autonomic neuropathy compared to controls, and in the whole observed population (diabetic and control subjects together), a significant correlation was found between HbA1c level and diastolic blood pressure. This finding is consistent with previous studies on diastolic blood pressure in childhood diabetes –75.It is well-known that hypomagnesemia is common in poorly controlled and chronically treated diabetic patients , 77. SevIn summary, at the time of transition from pediatric to adult-oriented health care in this young T1DM population, cardiovascular autonomic neuropathy and cardiac morphological differences could not be found. However, peripheral sensory neurological impairments with several modalities were detected among young type 1 diabetic patients. The results may provide important feedback to pediatric diabetes care and a remarkable baseline reference point for further follow-up in adult diabetes care.Continuous involvement of young T1DM patients following their entrance to the adult healthcare system and further enlargement of this specific study population is planned in the future. In addition, an annual follow-up of the already involved subjects is designed to estimate the progress of their neuropathic state. The listed medicines might also have an impact on the test results. Due to the low number of T1DM patients on oral antihypertensive therapy, a statistical analysis has not been feasible to perform yet. The echocardiographic examinations and the collection of the blood and urine samples due to logistical reasons were not possible from all the patients and controls.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Hungarian Medical Research Council. The patients/participants provided their written informed consent to participate in this study.AV, ÁM, ÉC, KS, IB, PK, AO, TV, and CL had substantial contributions to the conception of the work and design of the paper and read and approved the final manuscript. CP, DU-P, AN, MS, AO, and AV contributed to the measurements and analyses of data. AV, IB, PK, TV, AO, and CL drafted the paper or revised it critically for important intellectual content. All authors contributed to the article and approved the submitted version.This work was supported by the Ministry of Human Capacities of Hungary (EFOP-3.6.3-VEKOP-16-2017-00009), the Hungarian Diabetes Association, the University of Szeged Open Access Fund (Grant No. 5455), and by the National Research, Development and Innovation Office (NKFIH-K-128851).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Some investigations indicated that WS patients have stiffer large arteries2 while other studies showed that these patients have arteries with decreased stiffness,3 compared to unaffected persons. While the cardiovascular impact of WS is well known, the molecular pathways leading to altered blood pressure and arterial stiffness in patients with WS or mouse models of the cardiovascular features of WS stays puzzling.Williams–Beuren syndrome (WS) is caused by a large deletion in one of the chromosomes 7 (7q11.23), encompassing 26–28 genes, among which is the elastin gene.7 which suggests that the renin-angiotensin system could be involved in a basal vessel constriction level and account for the featured hypertension.Mice hemizygous for the elastin gene (Eln+/−), the most studied model of the cardiovascular features of WS, are hypertensive, with cardiac hypertrophy, and have stiffer, narrower, and longer large arteries.8 a new and major molecular cause of hypertension and arterial stiffening in mouse elastin insufficiency is uncovered, that is, reactive oxygen species (ROS). This is in accordance with the suggestions from previous studies which showed that, when the WS deletion included the NCF1 gene, then the patient's blood pressure and arterial stiffness were lower. The NCF1 gene encodes for p47phox, the regulatory subunit of the NADPH oxidase (NOX) complexes NOX1 and NOX2, which generate ROS in the vessel walls, leading to hypertension.9 These clinical findings have been confirmed by Troia et al. in Eln+/− mice, shown to have elevated vascular ROS production, and Eln+/−; Ncf1+/− mice, whose arterial cells produce less ROS than those from Eln+/− animals. Because of the specific geometry of the Eln+/− mouse arteries, that is, smaller caliber, longitudinal elongation, and subsequent tortuosity, the blood flow becomes turbulent and exerts a particular oscillatory shear stress on the vessel wall. This results in activation of the aortic endothelial and smooth muscle cells which produce more ROS. By crossing Eln+/− mice with either NOX1-/y or NOX2-/y animals, Troia et al. have also shown that NOX1 is the major contributor to ROS-induced elevation of blood pressure in Eln+/− animals. Indeed, compared to blood pressure in Eln+/− mice, deficiency in NOX1  induces a strong drop in systolic blood pressure, which is normalized to the level present in Eln+/+ mice, while only a slight trend towards a decrease in blood pressure could be observed in Eln+/−; NOX2-/y mice. Surprizingly, although arterial stiffness was found lower in Eln+/−; Ncf1+/− than in Eln+/− mice at the respective physiologic blood pressure of each group, no difference in the ascending aorta morphology and pressure-diameter relationship could be observed between Eln+/−, Eln+/−; Ncf1+/−, Eln+/−; NOX1-/y, and Eln+/−; NOX2-/y mice, or between Eln+/+, Eln+/+; Ncf1+/−, Eln+/+; NOX1-/y, and Eln+/+; NOX2-/y mice. However, it cannot be excluded that the involvement of NOX2 in the vessel mechanics, very low in the ascending aorta, could be greater in downstream parts of the vascular tree with a higher proportion of endothelial cells. This is suggested by our observation that, compared to wild-type animals, the abdominal aorta of NOX2-deficient mice presents modified pressure-diameter relationships, with narrower vessels in the 0-175 mmHg range and reduced extensibility  in the 50–100 mmHg range , is abolished by NOX1 deficiency  or after acute administration of the ROS scavenger tempol. This suggests that elimination of ROS, immediate (Tempol) or in the long term , is sufficient to normalize blood pressure, possibly by reversing the ROS-enhanced production/stability/activity of receptors to vasoconstrictors like PE . Given t2O2 in obese patients.10 Acute or chronic treatment with apocynin could therefore be considered for future clinical trials to lower blood pressure in WS patients.The work by Troia et al., by uncovering the role of NOX-generated ROS in WS-related hypertension, opens new therapeutical perspectives. Administration of apocynin to humans has already proved to lower tissular H


The evaluation and monitoring of patients’ haemodynamic parameters are essential in everyday clinical practice. The application of continuous, non-invasive measurement methods is a relatively recent solution. CNAP, ClearSight and many other technologies have been introduced to the market. The use of these techniques for assessing patient eligibility before cardiac procedures, as well as for intraoperative monitoring is currently being widely investigated. Their numerous advantages, including the simplicity of application, time- and cost-effectiveness, and the limited risk of infection, could enforce their further development and potential utility. However, some limitations and contradictions should also be discussed. The aim of this paper is to briefly describe the new findings, give practical examples of the clinical utility of these methods, compare them with invasive techniques, and review the literature on this subject. Recently, there has been a rapid development in non-invasive, haemodynamic monitoring technologies. As more and more devices enter the market, the availability of the new approach develops. Despite being often described as the ‘gold standard’, invasive methods can be associated with more complex procedures and the risk of complications, including infection. Therefore, the search for other solutions is necessary. The monitoring of haemodynamic parameters, especially cardiac output, is an essential element of clinical practice. Haemodynamics monitoring can be divided into three groups: invasive methods , less invasive methods  and non-invasive methods (without disrupting a patient’s skin and tissues) .This paper aims to analyse the commonly used techniques of haemodynamic parameters’ measurements and to describe the possibilities of currently available non-invasive methods.The accuracy of the non-invasive haemodynamic parameters’ measurements and their comparison to values obtained by the invasive methods, is crucial in clinical practice.2). This parameter allows for the indirect estimation of hypoxia and peripheral perfusion. Values below 65% are considered to be a sign of increased tissue oxygen consumption. This procedure is associated with the risk of severe complications, such as pulmonary artery dissection, right bundle branch block, and catheter-related infection [The most invasive, as well as the most precise, technique of haemodynamic parameters’ measurements is pulmonary artery catheterisation (PAC), using the Swan-Ganz catheter. It is inserted via the subclavian or internal jugular vein access and sequentially passes through the venous system into the right atrium of the right ventricle. Next, it is placed in the distal part of the pulmonary artery’s branch. At this location direct measurements can be made, including the cardiac output (CO), central venous pressure (CVP), right atrial and ventricular pressure, pulmonary artery pressure and pulmonary capillary wedge pressure (PCWP). The cardiac output is assessed using the thermodilution technique. A cold saline solution of a known volume and temperature is injected into the right atrium. Passing through the ventricle and into the pulmonary artery, the injectate mixes with the blood, cooling it. Then, a thermistor located at the catheter’s tip measures the blood temperature. Taking into account the temperature and volume of the saline solution, as well as the quantified change in blood temperature, a computer determines the thermodilution profile and calculates the right ventricular cardiac output. The procedure is often repeated and the measurement is averaged. Additionally, PAC enables the indirect measurements of many other haemodynamic parameters such as systemic vascular resistance (SVR), stroke index (SI), pulmonary vascular resistance . Anothernfection . The usenfection .2) and oxygen consumption (VO2) [A slightly less invasive way of obtaining haemodynamic parameters is a method using PiCCO (Pulse Contour Cardiac Output) technology . It combines a pulse wave contour analysis, the transpulmonary thermodilution method, as well as a venous blood saturation measurement. Thermodilution calibrates the pulse contour analysis in the individual patient. Two vascular accesses are necessary to perform the measurements: central venous access and arterial access via the femoral artery or, optionally, the axillary or brachial artery. A pulse wave contour analysis allows the marking of the CO, mean arterial pressure (MAP), stroke volume (SV), stroke volume variation (SVV), pulse pressure variation (PPV) and SVR values. On the other hand, using transpulmonary thermodilution enables the calculation of the CO, cardiac function (CFI), total end-diastolic volume, volume of excess extravascular water (EVLW) and complete stroke volume. However, oximetry provides several crucial parameters regarding the body’s oxygen management, including venous blood saturation in the superior vena cava, tissue oxygen delivery (DOon (VO2) . Despiteon (VO2) .ProAQT  is also used for waveform analysis. However, it does not rely on the thermodilution method and is generally less complex. It can be easily used for both femoral and radial accesses. Nevertheless, when compared with other methods, its inaccuracy and inferiority to thermodilution-based CO and SI measurements is noteworthy ,8. AdditAnother device allowing a less invasive haemodynamic parameters measurement is FloTrac™/Vigileo monitor™ . It is implemented via arterial access. The FloTrac system enabled the measuring of parameters such as: CO, SV, SVV, MAP and SVR. They were calculated based on 20 s measurements of SV and pulse pressure, which allowed for an almost real-time recording. The results obtained using the FloTrac device in cardiac surgery patients were comparable with those received via an invasive measurement with PAC . One of 2 and DO2I (oxygen delivery) [Lastly, LiDCO (Lithium dilution cardiac output) technology , which uses pulse wave analysis, is another less invasive technique. The LiDCO system requires a peripheral artery and central venous catheter . The calibration is conducted using the lithium oxide dilution method and is recommended every 8 h. Using this device, the following parameters can be recorded: CO, HR, MAP, CI, SV, SVR, SVRI, SVV, PPV, SPV (systolic blood pressure variations), DOelivery) .The continuous, non-invasive blood pressure measurement and the monitoring of haemodynamic parameters are assessed for every heart contraction (beat-to-beat mode). These procedures are of an entirely non-invasive character, meaning that they do not disrupt the skin or tissues. Nowadays, the market offers two systems: CNAP  and ClearSight .When applying these devices, one should start with entering the patient’s data such as sex, age, height and weight. The CNAP measurement requires two cuffs: one on the arm, and the other, a double cuff, on the index and middle finger. A plethysmographic sensor records the blood volume change in the finger. This allows the maintaining of the appropriate pressure in the arm’s cuff in order to sustain a consistent blood volume in the finger. This way, the pressure measured on the arm corresponds to the arterial blood pressure of every heartbeat, and the monitor shows its high-resolution dynamic curve in real time. Naturally, every measurement requires a prior device calibration with a standard oscillometric method (NIPC—Non-Invasive Pulse Co-oximeter) ,13. HoweNon-invasive measurements allow the assessment of the following :These values are calculated from the continuously registered pressure curve. Nevertheless, the absolute values are adjusted by the oscillometric measurement.2I), oxygen saturation (SpO2), HR, SVV, and non-invasive blood pressure (NIBP). Early studies present this technique as an alternative method of haemodynamic monitoring, since it is shown to provide similar values to those obtained via the pulmonary thermodilution method [NICCOMO  uses thoracic electrical bioimpedance (TEB) to calculate CO. A low amperage and high frequency electricity is transmitted through the chest. During systole, the increase in blood volume in the thorax lowers the resistance of the passing electricity. The impedance is measured via the electrodes placed along the electricity current. Several other parameters can be measured: CI, SV, SI, SVR and SVRI, oxygen delivery index (DOn method .TM (Non-Invasive Cardiac Output) can be applied [2 disturbance. Then, CO is calculated using the Fick CO2 equation. The values of CO, SV, and pulmonary capillary blood flow (PCBF) can be assessed. NICO measurements correspond relatively well with those obtained from using the thermodilution method [In patients supported by mechanical ventilation, NICO applied ,16. The n method .Several advantages of the non-invasive methods include: the patient’s safety, simplicity of application, shorter time until intervention, savings on expensive disposable materials used in invasive methods, and no risk of infection. The relatively limited accessibility of these devices could be considered a disadvantage. Using non-invasive measurements is contraindicated in the following situations: peripheral artery disease, diminished peripheral blood perfusion , frequent arrhythmias, vascular implants in upper limbs, tremor, and no guarantee of reliable readings in haemodynamically unstable patients ,18.A comprehensive comparison of invasive and non-invasive methods is presented in A study involving 21 patients after cardiac surgery, in whom CO was measured up to two hours after the procedure using PiCCO, FloTrac and LiDCO, in comparison with PAC, showed LiDCO as the most precise of the less invasive methods .Regarding the non-invasive methods of parameters measurement, two systems are currently available on the market: CNAP  and ClearSight . Notably, both are based on the volume-clamp method by Penaza . This meThe ClearSight system was compared with invasive methods in 10 trials with a population of 365 patients. The vast majority of authors showed a good correlation of CO and blood pressure values obtained by a non-invasive measurement with the ‘gold standard’; however, these studies did not meet the FDA’s (Food and Drug Administration) clinical interchangeability criteria . These oIt is worth mentioning that the non-invasive measurements were the most accurate in patients with high CO and low SVRI values, and the least accurate in patients with low CO and high SVRI values . The CleConversely, SBP, DBP and MAP measurements made by a CNAP device in a study of 2019, were considered as comparable, obtaining invasive measurements and meeting the criteria for their interchangeable use in stable patients remaining in an intensive care unit after cardiac surgery . SimilarHowever, a meta-analysis from 2014 of 28 studies, with 919 participants, involving various non-invasive haemodynamic monitoring devices showed inaccuracy and a lack of precision in SBP, DBP and MAP measurements, when compared with invasive monitoring . In respWhen the first devices for non-invasive haemodynamic monitoring entered the market, the research on their clinical application was initiated. Intensive care units and anesthesiologists became the main beneficiaries of the new devices, as they used them for intraoperative cardiovascular monitoring. Recently, TEB provided additional information regarding the haemodynamic alternations resulting from the induction of general anaesthesia . NonetheFurthermore, non-invasive monitoring enabled the observation of characteristic deviations in haemodynamic parameters in particular groups. A noticeable difference between SBP and DBP, as well as a high acceleration on the pulse wave sigmograph, were the characteristic features of aortic regurgitation A. In cirAlthough some of the new techniques seem promising for the paediatric population, data regarding this group of patients remains limited ,36.In surgical patients, haemodynamic instability can occur during the perioperative period, which is caused by the shift in the volume of the intravascular fluid, anaesthetics, and surgical intervention. Therefore, the fundamental aim of anaesthetic monitoring during surgical procedures is to control the haemodynamic parameters. The good credibility and equivalence of the haemodynamic measurements  obtained in the operating theatre via a non-invasive method, when compared to invasive methods, is noteworthy ,38,39.Using a constant, non-invasive arterial blood pressure measurement in patients with ClearSight under general anaesthesia undergoing non-cardiac surgeries decreased the hypotension time by half . These rIn another study, with patients undergoing complete hip or knee joint replacement surgeries, the fluid therapy scheme in the studied group was based on non-invasive haemodynamic monitoring, especially the pulse pressure variation (PPV) and, in the control group, fluid therapy was based on a standard oscillometric blood pressure measurement, every 5 min. The intraoperative fluid therapy under CNAP control resulted in a decreased number of postoperative complications (83% in the control vs. 55% in the studied group) and necessary blood products transfusion (75% patients in the control vs. 38% in the studied group). Moreover, the number of intraoperative hypotension episodes decreased by 33% in the studied group with a lower postoperative mean arterial blood pressure (MAP = 103 mmHg) compared to the control group (MAP = 118 mmHg) . CNAP moFurthermore, a high correlation of non-invasive PPV measurements, when compared with invasive methods, is shown ,48. ThesMoreover, there is no direct comparison of clinical applications in both non-invasive monitoring systems, CNAP and ClearSight.Another important group of patients, in whom haemodynamic monitoring is essential, are patients undergoing cardiosurgical procedures. In haemodynamically stable patients undergoing coronary artery bypass grafting (CABG), postoperative cardiac output values measured by a non-invasive technique were comparable to those measured via an invasive PiCCO method ,51 and tIn a study of 33 patients with severe aortic stenosis undergoing percutaneous aortic valve implantation (TAVI) via transfemoral access, no significant differences were found in the accuracy of blood pressure measurements using a non-invasive method (CNAP) and an invasive  method. Furthermore, the non-invasive blood pressure measurement during fast heart stimulation, accurately and immediately showed significant alternations in the haemodynamic parameters . SimilarApart from these findings, there are very limited data showing any clinical benefits, including patient outcomes and cost effectiveness, from using non-invasive hemodynamic monitoring.Haemodynamic monitoring is essential for patients in critical condition and for those requiring intensive care. The studies regarding the utility of non-invasive haemodynamic monitoring methods in this population gave contradictory conclusions. The research involving 40 intensive care unit patients showed an accuracy of non-invasive monitoring blood pressure measurements when compared to the invasive measurements . AnotherRegarding cardiology, non-invasive haemodynamic monitoring techniques were tested on a group of 84 heart failure patients, mainly NYHA III and IV; the mean ejection fraction was 27%. The non-invasive measurement of cardiac output compared to the thermodilution method was revealed to be overestimating and not recommended for this population . DespiteThe clinical utility of NICCOMO in intensive care unit patients requires further investigation as the data regarding this matter are limited .Considering the complexity of procedures and the possible severe complications associated with invasive haemodynamic monitoring, alternative solutions are being widely explored. Non-invasive methods were found to be successful in numerous areas. In surgical patients, they were used for intraoperative cardiovascular monitoring and the early detection of haemodynamic alternations, as well as for adjusting the fluid therapy. Furthermore, a reduction in postsurgical complications was noted. These findings come from various hospital wards, other than the cardiac department, including anaesthesiology, orthopaedic surgery and gynaecology wards. Even though a wide range of parameters can be obtained, in some cases an invasive approach is necessary. This includes not only critically ill patients, but also those in shock or suffering from heart failure. Nevertheless, in some patients, the implementation of the non-invasive methods might be the missing link between an invasive approach, such as thermodilution, and a simple oscillometric cuff measurement. Hence, patients with non-cardiac conditions which severely alter their hemodynamic state, e.g., cirrhosis and chronic kidney disease, should be the next potential group that could benefit from non-invasive hemodynamic monitoring and require further investigation.The data regarding monitoring patients in intensive care units, using new technologies, remain contradictory and require more studies. Moreover, it is crucial to further investigate how these non-invasive techniques could influence the therapeutic decision-making process and patients’ prognoses, as well as analyse the economic aspects of these interventions. In addition, other potential clinical practice applications should also be widely explored. Furthermore, a substantial need for establishing and standardizing the evaluation criteria of non-invasive haemodynamic monitoring devices is noted. The current criteria were initially applied only to oscillometric temporary measurements. Therefore, they seem to not be applicable in evaluating the constant, non-invasive measurements of the haemodynamic parameters ,32.Finally, the approach to choose the right method should always be individually tailored to the patient and still recognize the contradictions, as well as the limitations.


We have identified several parameters to monitor in order to compare how well the CAP sensor tracks the entire hemodynamic waveform as compared to the A-Line. This includes waveform similarity, heart rate (HR), absolute systolic BP (SBP), diastolic BP (DBP), and temporal response to a vasopressor. Overall, the CAP sensor shows good correlations with A-Line with respect to hemodynamic shape (r > 0.89), HR , absolute SBP, and DBP in a line of best fit  and the mean bias derived from Bland-Altman method to be 1.92 (SD = 12.55) in SBP and 2.38 (SD = 12.19) in DBP across body habitus and age in OR patients under general anesthesia. While we do observe drifts in the system, we still obtain decent correlations with respect to the A-Line as evidenced by excellent linear fit and low mean bias across patients. When we post-process using a different calibration method to account for the drift, the mean bias and SD improve dramatically to −1.85 and 7.19 DBP as well as 1.43 and 7.43 SBP, respectively, indicating a promising potential for improvement when we integrate strategies to account for movement identified by our integrated accelerometer data.We test a new wireless soft capacitance sensor (CAP) based on applanation tonometry at the radial and dorsalis pedis arteries against the gold standard, invasive arterial line (A-Line), for continuous beat to beat blood pressure (BP) measurements in the Operating Room during surgical procedures under anesthesia in 17 subjects with the mean age and body mass index (BMI) of 57. 35 ± 18.72 years and 27.36 ± 4.20 kg/m Blood pressure (BP) is one of the core physiological measurements of interest in virtually all healthcare contexts as it provides insight into a patient's cardiac function, volume status, organ perfusion, and overall hemodynamic stability. It is typically monitored using a non-invasive sphygmomanometer, otherwise known as the BP cuff, and in higher-risk surgery may be monitored using an invasive arterial line. The arterial line (A-Line) is considered the gold standard in capturing beat-to-beat BP values to detect immediate fluctuations. This requires the insertion of a catheter into an artery, typically the radial or dorsalis pedis arteries. Because A-Lines are invasive, they are associated with an increased risk of complications including infection, thrombosis, and embolization –3. CliniInstead, the overwhelming majority of patients even in hospital settings are only monitored intermittently using the BP cuff, which inherently lacks the temporal resolution to detect real-time fluctuations in hemodynamically labile patients. Moreover, such intermittent measurements have been observed to under or overestimate BP readings when compared with the A-Line , 6. In fSince blood pressure is a dynamic physiological parameter that changes constantly over time, non-invasive continuous blood pressure monitoring would reveal important hemodynamic information in real-time that is currently delayed by the intermittent BP cuff readings. This is especially important when labile BP warrants close monitoring–such as in the Emergency Room (ER), OR, or ICU settings. Furthermore, as healthcare moves towardz digital health, options for remote continuous BP monitoring  would be incredibly useful in the management of hypertension, which affects roughly half of all American adults, as well as other medical conditions with vascular underpinnings . This isFor these reasons, non-invasive methods for continuous BP monitoring, or non-invasive blood pressure (NIBP), is an area of continued interest. Existing NIBP methods to capture continuous BP include optical techniques; derivations based on other vital sign measurements [such as pulse transit time (PTT)]; ultrasound technology; and tonometry. Concerning optical techniques, ClearSight  and CNAP  are both FDA-approved infrared photoplethysmography (PPG) devices that use the finger cuff volume clamp method. These devices are used preliminarily in the ICU or post-operative patients in the hospital because patients must remain stationary, the method is uncomfortable (a finger cuff repeatedly inflates), and they do not work well on patients with peripheral vascular disease or administration of high dose vasopressors –11. More2. Importantly, to do our comparison, we needed to develop an objective signal processing framework to analyze large data sets of different length scales with real-world noise and motion artifacts. Moreover, to make sense of the data, we needed to determine strategies to compare key parameters.We have previously demonstrated the accuracy of a soft wearable capacitance sensor (CAP sensor) based on applanation tonometry for continuous non-invasive measurement of BP compared to the FDA-approved NIBP monitor Clearsight in a small cohort of healthy, young individuals . For cliBP data were acquired invasively and non-invasively using an A-Line and a CAP sensor, respectively. Surgical patients aged 18 to 99 years under general anesthesia in the OR setting who needed an A-Line placed as a standard of care were recruited at University of California Irvine Health between June 2020 and March 2021. Exclusion criteria were patients aged <18 years, refusal, or inability to give informed consent. All subjects gave informed consent for the study which was approved by the Institutional Review Board of the University of California (IRB no. 2019-5251).© IV Monitoring Kit (60″), REF no. 42584-05] and displayed on a monitoring system . The A-Line signal was then captured at an average sampling rate of 100 Hz using a DAQ board  with a custom application written in C#.This study simultaneously employed two continuous BP measurement systems . The A-LThe non-invasive system comprises a soft capacitive pressure sensor (CAP)  and an EThe A-Line was inserted into the radial artery on either arm and calibrated per hospital protocol. A BP cuff  was also placed on either arm for periodic measurements. The CAP sensor was placed over the radial artery, on the arm without the A-Line, and stabilized with slight pressure via mechanical fixation using velcro strap, sea-band , or Prelude Sync Radial Compression Device . In cases where the radial artery was not readily available for placement, the dorsalis pedis artery was used . The EcoAfter anesthesia induction, measurements were continuously collected from both CAP (non-invasive) and A-Line (invasive) systems by the anesthesiologist for a minimum of 15 min during the operation. The timing of administration of all intraoperative vasoactive medications was recorded in the electronic medical records (EMR).The collected data was post-processed using Matlab . The raw signals were first spline interpolated to 500 Hz. To synchronize the signals recorded on different systems, cross-correlation was applied to the signal obtained by differentiating the discrete sequence of systolic peaks. After signal synchronization, clearly identified artifacts from invasive and non-invasive measurements were cleaned out. The A-Line data was visually screened by the authors for errors; excessively noisy sections defined by a sudden change of pressure >30 mm of mercury (mmHg) within two beats were removed. On the other hand, artifacts in the CAP signals were removed based on the movement data captured by the IMU. A 2.5-scaled median absolute deviation (MAD) filter was applied to accelerometer data on each of the 3 axes to detect outliers due to sudden and immoderate movement . A 100-pThe diastolic and systolic pressure values and timestamps of each valid segment of data were identified for waveform analysis. A complete waveform was defined as the signal data bounded by two consecutive diastolic pressure values.To analyze waveform shape similarity, corresponding A-Line and CAP sensor waveforms were normalized between 0 and 1. For each waveform, 0 was set as the average of the starting and ending diastolic pressure values, and 1 as the waveform maximum . A 0.1 threshold value was then applied to avoid false detection of minima (diastolic pressure).HR is the reciprocal of the beat-to-beat time interval of the continuous blood pressure signal (Equation 1). The systolic intervals were obtained as the time interval from one systolic pressure value to the subsequent one as shown in The accuracy of HR estimation from capacitive pressure signal was evaluated by computing average HR values in each 30-s data window from valid segments of CAP sensor and then comparing against A-Line's. Each valid signal was sliced into 30-s non-overlapping windows starting from the beginning of the signal and any remaining data that was <30-s was excluded from HR computation.Using valid data segments from A-Line and CAP sensor measurements, the CAP sensor's ability to accurately infer absolute BP is assessed.Given that the CAP sensor's raw measurements are captured as capacitance values in picofarad (pF) and the A-Line's as absolute pressure in mmHg, a conversion from the CAP sensor's capacitance to absolute pressure in mmHg is needed to accurately assess the CAP sensor against A-Line. In this regard, we propose a calibration algorithm.The initial step in the calibration process is the extraction of systolic and diastolic pressure signals from the raw A-Line and CAP sensor measurements. A 5-points median filter was applied to the extracted signals to smooth out detected false values. The filtered systolic and diastolic pressure signals were then split into individual 60-s segments for use in subsequent calibration steps. In a normal resting condition, a 60-s segment should contain 60–100 beats. The choice of 60-s as segment length is based on ClearSight's use of 70 beats between re-calibration .The calibration algorithm took the average values of the first three beats in systolic and diastolic pressure every 60-s epoch. Sixty seconds was chosen for re-calibration periodicity as this is standard practice in ClearSight, a commercially available continuous NIBP device. A linear regression model was then created as the relationship between pressure measured in pF and mmHg. The remaining systolic and diastolic capacitance pressure values in the 60-s segment were then converted to the units of BP (mmHg). An example of the calibration algorithm can be found in r was computed to quantify the similarity between corresponding A-Line and CAP sensor normalized waveforms after aligning the two by their maxima  and how well the CAP sensor tracked BP compared to A-Line in vasoactive-drug-administered incidents. Moreover, the mean bias, SD, and 95% limits of agreement (estimated as the SD of the differences × 1.96) were calculated to understand the agreement between two methods by Bland-Altman method of paired measurements , five were excluded with obvious distortion in the measurements (artifacts or inaccurate sensor placement), and three others were excluded when the pulse signal from dorsalis pedis was affected by the intermittent pneumatic compression (IPC) device placed on the legs during the entire measurement. Thereafter, 17 patients  with the mean age of 57.35 ± 18.72 years and mean body mass index (BMI) of 27.36 ± 4.20 kg/mThe post-processing method was used to remove obvious incorrect measurements and potential distortion affected by apparent artifacts. After removing for artifacts as heretofore described, the mean and standard deviation of the total amount of data included across the 17 studies was 46 ± 21%.r is applied to indicate the strength of similarity between the two curves. Due to the length difference of valid segments in each dataset, the results are presented as averaged r-values with the quantity of full-beat waveforms as listed in r lower than 0.9 (Subject 2 and Subject 14) were the only two studies having the pressure sensor placed on dorsalis pedis artery rather than the radial artery.All the full-beat waveforms were included to understand the similarity of hemodynamic waveforms from two sites of the subject's body. A total of 20,090 full-beat waveforms were analyzed, which included non-invasive pulse waveforms from the radial artery and dorsalis pedis artery, to compare against BP derived from A-Line. Pearson's To assess the accuracy of heart rate detection across all the patients in the study, a total of 562 30-s valid segments for both A-Line and CAP were extracted and compared in the mean and standard deviation of heart rate. The mean bias and SD of mean HR in two measurements are 0.0006 and 0.1666 bpm, respectively. The 95% limits of agreement lie in the range of −0.3259 and 0.3272 bpm .A total of 29,319 BP values  were obtained and compared from 209 60-s segments. The mean bias of overall DBP and SBP are 2.3842 (SD = 12.1908) and 1.9153 (SD = 12.5525), respectively. The limits of agreement in DBP are from −21.5098 to 26.2782 mmHg and for SBP from −22.6876 to 26.5182 mmHg . To under of SBP between A-Line and CAP was 0.82 ± 0.28 (mean±SD). Lastly, we observed the BP change after the vasoactive drugs were administered. A total of 20 events were identified according to physician observation and the EMR across nine patients (no vasoactive drug administration was observed while the other eight patients were recorded). Three events were excluded due to movement artifacts caused by either the surgeon or the periodic BP cuff measurement. The mean duration of the 17 events was 55.4 (SD = 29.8) seconds. The Pearson's The major finding of the study is that the CAP sensor can non-invasively track BP across different body types and ages in an OR setting under general anesthesia. In particular, the study showed the sensor's capability of capturing hemodynamic waveforms from different arterial sites with high fidelity compared to the A-Line. Additionally, we found a good correlation in HR monitoring. Concerning beat-to-beat BP monitoring, we showed a low mean bias of both SBP and DBP.At present, we have demonstrated an ability to accurately track blood pressure with high confidence. While the present performance may be improved over time and is not a replacement for continuous arterial monitoring, there would nevertheless be clinical utility even with the present sensor as an adjunct to non-invasive monitoring . The NIBP monitoring could be used as it currently is, and the CAP sensor recalibrated with each cycling of the non-invasive cuff. Meanwhile, the CAP sensor would provide continuous monitoring in the periods between cuff cycles, catching hypotension faster and allowing for more rapid treatment, as well as allowing for more rapid assessment of other interventions like narcotics or anti-hypertensives.Fifteen out of 32 datasets had been excluded from the study for the following reasons: failure of data collection, obvious distortion (in the A-line data or from obvious misplacement of the CAP), and the simultaneous use of the IPC device. Improved instructions on applying the CAP sensor and/or improved applanation (strap) design should improve the ability to capture more datasets in the future.As previously mentioned, the 17 studies had been done either using a single or dual-channel CAP sensor. For the dual-channel CAP sensor, the second channel may be useful as a neighbor reference of the main arterial pressure signal. However, we have not yet investigated the benefits of dual-channel acquisitions and as a result, only one capacitance reading is included for all the data analysis in the study. We believe a multi-channel CAP sensor will greatly improve blood pressure monitoring by eliminating the need for frequent recalibrations.There are a number of confounding factors inherent in any continuous physiological monitoring. This study was done in an OR setting to investigate the validity of the CAP sensor for a specific reason: we can account for and eliminate many of these variables. For instance, we have the BMI of every patient and whether they have hypertension via EMR. We found no correlation between BMI or hypertension and signal accuracy. The other major confounding factor is movement artifact.From the development of the CAP sensor, it was found to have a low tolerance to movements. Compared to the previous study published using the CAP sensor in a relatively controlled subject group, this study was done in a real clinical setting where the measurement could be affected by multiple challenges.One obvious difference of BP measurement with non-invasive technology is that the data is obtained outside the subject's body. With different body sizes and ages of a patient, the tissue layer between the CAP sensor and the artery may create artifacts that directly influence the pressure measurement. For instance, the mechanical fixation on an elder patient with loose skin can be more challenging. Besides, the tightness and positioning of the wristband affected the signal quality. This also explains the reason why the study included multiple mechanical fixation ways.Furthermore, human-caused artifacts such as the surgeon's need to interact with the patient's body or the interference from electronic noises were inevitable in the OR. We chose to remove the artifacts of the A-Line signal by eye considering limited information. A similar data exclusion method has been previously used by several other groups , 25, 26.We also observed baseline drift in some datasets from the CAP signal. In most cases, a downward drift occurred linearly or exponentially. The cause might be due to the movement or unknown factors. We expect a future study to resolve the issue. Despite the aforementioned challenges, it is clear that after the objective signal processing strategy outlined above, the CAP sensor showed a good correlation with A-Line during surgery and can provide a wealth of information about the hemodynamic waveform. In addition to the excellent slope value, the average mean bias and standard deviation across 15 patients were low.Pearson correlation was used to evaluate the degree of the linear relationship between A-Line and CAP waveforms. Similar work had been previously done .In this study, the focus for waveform similarity analysis was to compare full-beat wave shape. Consequently, the waveforms were normalized and aligned by the systolic pressure to avoid the time delay due to measuring from different sites of the body. A very strong correlation between A-Line and CAP sensor measurements was reported. Although not all waveforms from both signals perfectly match visually , it is iThe current study is subject to several limitations. Because this is a retrospective study, we went back to calibrate to the A-Line, after completion of data collection. Going forward, a sensor that calibrates to the BP cuff in real-time would be advantageous. The greatest challenge that we had was accounting for motion artifacts and drifts in the signal after motion. We, therefore, had to splice out many sections of the data to account for active movement as captured by the accelerometer. However, outside the window that we spliced out (during active movement), we observed the movement caused a longer-term drift over time. We did not account for such drifts in our analysis but had we done so, the results would be even better. This is evidenced by the fact that if we instead calibrated to the first, middle, and last point of each 60-s epoch (instead of just the average of the first three beats), the averaged mean bias and average SD go down considerably, from 2.3842 ± 12.1908 to −1.8477 ± 7.1906 in DBP and from 1.9153 ± 12.5525 to 1.4324 ± 7.4321 in SBP . This inOverall, in summary, we show that the CAP sensor is a promising technology that has good agreement with the A-Line regarding the hemodynamic shape, heart rate, SBP, and DBP across body habitus and age in OR patients under general anesthesia. While we do observe drifts in the system, we still obtain good correlations with respect to the A-Line as evidenced by excellent linear fit and averaged mean bias and standard deviation across all patients. Moreover, CAP seems to be able to track fast changes in blood pressure well, which is critical to monitoring hemodynamically unstable patients.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by University of California Irvine Institutional Review Board. The patients/participants provided their written informed consent to participate in this study.JR: study design, lead investigator of IRB, data collection and overseeing all data collection and signal processing, and paper writing. HM and NP: data collection. E-FC and SC: data analysis and writing. MK: data analysis, writing, and providing sensors. All authors contributed to the article and approved the submitted version.MK has financial interests in Vena Vitals as the scientific co-founder of the company and as such, owns equity in Vena Vitals, which is in addition to her salary from the University of California, Irvine. The nature of this financial interest and the design of the study have been reviewed by the UCI Conflict of Interest Oversight Committee (COIOC). The COIOC has determined that the researcher's financial interests are appropriately managed to avoid compromising the quality or reliability of the study and furthermore, the UCI Institutional Review Board has determined that appropriate safeguards are in place to avoid adversely affecting your safety and welfare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Hypertension is one of the most prevalent cardiovascular diseases and its treatment requires multimodal therapeutic approaches. This review aims to provide a summary and update on relevant evidence in hypertension research published in 2019/2020. These include trials dealing with the prognostic effect of systolic and diastolic blood pressure values, the association between hypertension and valve disease, reproducibility of masked and white-coat hypertension, and the prognostic importance of ambulatory and night-time blood pressure measurements. Treatment of hypertension focusing on elderly patients but also the potential cancer risk of thiazide diuretics, the valsartan recall, chronotherapy, and device-based hypertension therapy are discussed. Arterial hypertension is the most frequent modifiable risk factor associated with cardiovascular morbidity and mortality . DespiteHigh SBP and DBP associate with increased CV events. However, it remained unclear whether either SBP or DBP carries more prognostic information. This question was addressed in a study, which evaluated data from an integrated health care delivery system in the US. Between 2007 and 2016, more than 36 million office BP measurements were analyzed from around 1.3 million people [The 2017 American College of Cardiology and American Heart Association Guidelines on the management of hypertension revised the definition of hypertension , which hSBP and DBP are independently associated with myocardial infarction and stroke, although SBP has a greater prognostic effect. The J-curve relationship between DBP and the composite outcome was strongly influenced by age and coexisting conditions such as high SBP, diabetes, coronary disease, smoking, and history of stroke.p = 0.002), for aortic regurgitation by 2.5 , and for mitral valve regurgitation by 2.2 , respectively. An increase in SBP by 20 mmHg was associated with an almost 3-fold higher risk to develop any of the three valvular diseases  . Higher 24-h and night-time BP measurements were significantly associated with greater risks of death and the composite CV outcome  and white-coat hypertension . The reproducibility of these BP phenotypes, however, is not well known. In an analysis of 1664 hypertensive patients who were treated with atenolol or lacidipine for four years as part of the European Lacidipine Study on Atherosclerosis (ELSA) , the repThe overall reproducibility of masked and white-coat hypertension is low and suggests that regular BP examinations  are necessary.According to recent guidelines, treatment of hypertension in patients aged over 80 years should be initiated when BP is ≥160/≥90 mmHg  evaluated data of 4.9 million patients from 9 different databases in the USA, South Korea, Germany and Japan, in which treatment of hypertension was initiated with a single drug . A totalOne of the limitations of this analysis is the retrospective design. Physicians might have preferred ACE-I over a diuretic in patients with increased CV risk. That would explain why the effects on CV diseases in this group are more significant compared with the ACE-I-group. Furthermore, patients were treated with monotherapy, which is no longer recommended. Lastly, information about adherence to therapy and BP data are missing.Hydrochlorothiazide (HCT) is rarely used as a monotherapy but is a frequent component of double or triple combination preparations. The effectiveness of HCT compared with other thiazide-like diuretics has been the subject of controversial discussions , 17. TheThe Drug Commission of the German Medical Association does not recommend a general change in therapy for all HCT-treated patients, but individual examination and regular skin inspections. Chlorthalidone and indapamide are possible alternatives, but no data are available on the potential risk for skin cancer of these thiazide-like diuretics .Since early July 2018, products containing valsartan have been recalled worldwide. The reason is the detection of a known carcinogen, namely N-nitrosodimethylamine (NDMA), which can be found in candesartan, irbesartan, losartan, olmesartan, and valsartan. NDMA has been classified by the WHO International Agency for Research on Cancer to be carcinogenic in humans . The recp = 0.020) and hospitalization for stroke/TIA of 8% (p = 0.037) , doxazosin  or bisoprolol . The side effect profile of the substances was comparable over the 3-month investigation period. Thus, spironolactone has been recommended as a fourth-line therapy in patients with uncontrolled hypertension. The use of spironolactone, however, is often limited by hyperkalemia, which is associated with increased mortality.The PATHWAY-2  trial wa2, and the serum potassium between 4.3 and 5.1 mmol/L. All patients received spironolactone (25–50 mg) and patiromer (8.4 g) or placebo. After 12 weeks, therapy with spironolactone could be continued in 66% of the patients in the control group and 86% of the patients in the patiromer group  . The side effects were comparable between the two groups. Although a higher dose of spironolactone was administered over a longer period in the patiromer arm, the BP change was not statistically significant between the groups   lowers serum potassium levels and thus may be useful in patients with medication-related hyperkalemia. In the AMBER trial , patirom01) Fig. . The cumCompared with placebo, patiromer enables administration of spironolactone in more patients with therapy-resistant hypertension and renal insufficiency. However, the use of patiromer in addition with spironolactone was not associated with improved BP control. The long-term effects of a therapy with patiromer (>12 weeks) are unknown.p < 0.001; office DBP: 82.4 vs. 81.4 mmHg, p < 0.001; night-time SBP 118 vs. 114.7 mmHg, p < 0.001). There were also significant differences regarding the substances used in the groups . However, there are other studies that did not show an advantage of the chronotherapy. There are also major limitations in the study design which questions the transfer of the results into routine clinical practice based on the trial’s results alone.After early clinical trials , 32 and The SPYRAL HTN-OFF MED Pivotal trial demonstrated the superiority of catheter-based renal denervation compared with sham control to safely lower BP in the absence of antihypertensive medications.SBP and DBP are independently associated with myocardial infarction and stroke, although SBP has a greater prognostic effect.Studies show an association between hypertension and valvular heart disease outcomes. It remains to be seen how BP control may affect the incidence of heart valve disease progression.Twenty-four hours and night-time BP measurements were associated with greater risks of mortality and a composite of CV outcome. Thus, they may be considered as the most relevant measurements for estimating CV risk.The overall reproducibility of masked and white-coat hypertension is low and suggests that regular BP examinations  are necessary especially in these patients.BP values ≤140/90 mmHg may be associated with an increased risk of mortality in octogenarians or elderly patients with previous cardiovascular events.The risk-benefit assessment of an intensified BP treatment should be critically and individually evaluated, especially in older patients.Compared with placebo, patiromer enables the administration of spironolactone in more patients with therapy-resistant hypertension and renal insufficiency.However, the use of patiromer in addition with spironolactone was not associated with improved BP control.The Hygia study represents the largest study that tested night-time antihypertensive treatment. In this trial, chronotherapy was associated with a significant reduction in endpoints (including death). However, there are other studies that did not show an advantage of the chronotherapy. There are also major limitations in the study design which question the transfer of the results into routine clinical practice based on the trial’s results alone.SPYRAL HTN-OFF MED Pivotal trial demonstrated the superiority of catheter-based renal denervation compared with sham control to safely lower BP in the absence of antihypertensive medications.