This study aimed at assessing the incidence of pulmonary hypertension (PH) at newly diagnosed hyperthyroid patients and at finding a simple model showing the complex functional relation between pulmonary hypertension in hyperthyroidism and the factors causing it.The 53 hyperthyroid patients (H-group) were evaluated mainly by using an echocardiographical method and compared with 35 euthyroid (E-group) and 25 healthy people (C-group). In order to identify the factors causing pulmonary hypertension the statistical method of comparing the values of arithmetical means is used. The functional relation between the two random variables (PAPs and each of the factors determining it within our research study) can be expressed by linear or non-linear function. By applying the linear regression method described by a first-degree equation the line of regression (linear model) has been determined; by applying the non-linear regression method described by a second degree equation, a parabola-type curve of regression  has been determined. We made the comparison and the validation of these two models by calculating the determination coefficient (criterion 1), the comparison of residuals (criterion 2), application of AIC criterion (criterion 3) and use of F-test (criterion 4).From the H-group, 47% have pulmonary hypertension completely reversible when obtaining euthyroidism. The factors causing pulmonary hypertension were identified: previously known- level of free thyroxin, pulmonary vascular resistance, cardiac output; new factors identified in this study- pretreatment period, age, systolic blood pressure. According to the four criteria and to the clinical judgment, we consider that the polynomial model  is better than the linear one.The better model showing the functional relation between the pulmonary hypertension in hyperthyroidism and the factors identified in this study is given by a polynomial equation of second degree where the parabola is its graphical representation. Pulmonary hypertension on hyperthyroid patients is one of the most recent and up-to-date research topics. The guidelines for diagnosis and pulmonary hypertension treatment published in 201552 usually calculated by using the linear regression method. This one suggests the fact that the relation of determination between two variables is either increasing or decreasing, namely, a limitless relation. For human bodies, there are some limits of viability that cannot be surpassed. Nevertheless, the relation of determination cannot be linear as physiological mechanisms of adaptation and regulation intervene and model this line.These studies show that pulmonary hypertension on hyperthyroid patients is mainly determined by the hormonal excess and the increased cardiac output (CO) and pulmonary vascular resistance (PVR). Also, the same studies suggest that autoimmunityThe study, aims at assessing the incidence of pulmonary hypertension (PH) at newly diagnosed hyperthyroid patients and at finding a simple model showing the complex functional relation between pulmonary hypertension in hyperthyroidism and the factors causing it.Our research study was approved by the Transilvania University of Brasov, Ethics Committee. It has taken place over a period of 12 months, in 2015/2016, on newly diagnosed hyperthyroid patients’ who presented in endocrinology ambulatory and sent for enrollment to Medical Semiology Discipline.Inclusion criteria have consisted of clinical manifested hyperthyroidism, newly diagnosed, under the age of 50 (18-48 years), without any cardiovascular, pulmonary, autoimmune disease associated. Only 53 hyperthyroid patients signed the informed consent, and only 35 came back for follow-up appointments, after 12 weeks in euthyroid clinical status. Therefore, in this research, we used a hyperthyroid group , a euthyroid group  and a control group .The design of the study consisted in a determination of hormonal profile, an M and 2D Echocardiography combined with a tissue and spectral Doppler followed by the installment of a 24h EKG Holter and ABMP for 24 hour. These investigations were applied to the H-group, at the moment of inclusion, after 12 weeks of anti-thyroid treatment when euthyroidism by installing (thus becoming group E), and to the C-group at the time of enrollment.4) was detected by chemiluminescence method with the normal value of 10-23 pmol/l.For hormonal analysis, we used an ARCHITECT machine . Free thyroxin , we used Lindquist formula.PVR=(PAPm-10)/CO, where: PVR = pulmonary vascular resistance, PAPm = median pressure in the pulmonary artery, CO = cardiac output.The median pressure in the pulmonary artery was calculated using the following formula:PAPm=0.61 x PAPs+2 mm Hg, where: PAPm= median pressure in the pulmonary artery, PAPs = systolic pressure in the pulmonary artery.PH is defined as PAPm≥25 mm Hg at restIf the ratio E/E’>11 and the left ventricle ejection fraction is normal, that is more than 50% (LVEF≥50%), or if the ration E/E’>15 and the left ventricle ejection fraction is low, under 50% (LVEF<50%) then PAWP is increased.1PAP can be estimated from continuous wave Doppler measurements. Echocardiography is performed when pulmonary hypertension is suspected and may be used to determine a diagnosis of PH in patients in whom multiple different echocardiographic measurements led to the same diagnosis. Echocardiography is recommended as a first-line non-invasive diagnostic investigation of PH, when suspected, first class indication evidence level C.For EKG/24 hour HOLTER recording we used a “Schiller AG, MT-100”. In this paper, we only used the means values of the heart rate/24 hours (HR/24h).For ABPM/24 hours recording we used a Meditech ABPM-5 device. In this study, we utilized only mean values of systolic blood pressure/24 hours (systolic BP/24h).https://www.medcalc.org; 2017). In our tables below, the measured parameters are presented as mean values±S.D. (standard deviation). We applied the t-test for the statistical significance and χ2 Chi-squared test to study the Normal distribution.We use the program MedCalc Statistical Software version 17 .The linearb is the slope and a is a constant (intercept) of the line), relation being always graphically expressed by a line.9The functional relation between the two random variables can be linear, named a basic linear regression, described using a first degree equation y=a+bx  on either regression line or the regression curve are called residuals.92.2 (in terms of percentage) expresses the percentage of the variability of the outcome (PAPs in our study) that can be explained by the predictor.The best model taken into consideration is that where the error  sum of squares (SSE) is the least.2 suggests a better model. If the residuals and R2 register close values for the two models, then, we can distinguish which of the two models is the most convenient consequently, a F-test (applied for nested model)Generally, for these two models, the higher value of the coefficient of determination RThe method AIC determines the way in which the data supports each model, taking into account both the residual-sum-of-squares and the number of parameters in the model.9Mean values ±S.D. of the measured parameters, in the three groups , the statistical significance of the means comparison , are shown in 4, CO and PVR, are also increased in the hyperthyroid group, at a significant level. Left ventricular ejection fraction (LVEF) and heart rate (HR) are main determinants of CO and are raised to in the H-group, at a significant level. We also observed significantly high values of systolic BP. Similar values in the E- and C-group, for all these parameters, suggest that PVR, CO, HR, LVEF, systolic BP values normalize when obtaining euthyroidism. According to the 2013 ESH/ESC guidelines for the management of arterial hypertension, 24 hyperthyroid patients have fulfilled criteria for arterial hypertension (45.2%).The values of main determinants of PAPs, FTMeasured parameters in the H-group with PH comparing with the ones without PH are shown in 34 levelly is lower than at the patients without PH  but have Graves’ disease in similar percentage (80.7% versus 77.7%) than the hyperthyroid patients without PH. Those facts suggest that age, pretreatment period and systolic blood pressure can also be determinant for PAPs if we demonstrate the existence of a relationship between them.4, has the highest level of HR, the best LVEF, CO, PAPs, PVR and the highest systolic BP. With each decade of age, at similar levels or even increased levels of FT4, the PAPs, PVR, CO, LVEF and the systolic BP/24h drops.The main hemodynamic characteristics of the hyperthyroid group, age groups, as mean values ±S.D, are presented in 4, Pretreatment period and Age, are graphically represented by the regression line in squares A,B,C in comparison with the parabola-type regression (non-linear regression) in the squares A’, B’, C’. In the  non-linear regression, the higher the coefficients of determination of PAPs is improved  the higher level of significance of determination in comparison with the linear regression is. The parabola scatters diagram aspect is sustained by the clinical judgment. The peak of the parabola  improves coefficients of regression R2 and their level of significance compared to the method of linear regression that uses a first degree equation “y=a+bx” .The method of polynomial regression according to the second degree equation “y=a+bx+cx2 are higher; b) residual sum of squares for polynomial regression are smaller than the residual sum of squares for linear regression highlighting the fact that the difference between the measured values and the values obtained through the polynomial model  are lower; c) ΔAIC has negative values and the more complicated model (parabola type one) is considered to be better.The comparative analysis between the linear regression model and non-linear regression one (in our study being a parabola type) regarding the relation of determination of pulmonary pressure in hyperthyroidism shows that the polynomial model is better than the linear one in all situations because a) the coefficients of determination RHarvey Motulsky and Arthur ChristopoulosPAPs has not been determined in an invasive manner, through catheterism, which is the method indicated for diagnosing HP in present guide, but HP was estimated through a echocardiographic method. Echocardiography is a less precise method through which one may overestimate a normal pulmonary pressure and may underestimate a severe pulmonary hypertension. We have to mention that the invasive measurement of PAPs in hyperthyroidism is not correct from an ethical point of view.The comparative analyses between linear and non-linear regression designed for creating a model of determining the pulmonary pressure in hyperthyroidism shows that the non-linear model is the most appropriate. The model of determining the pulmonary pressure in hyperthyroidism is a polynomial model represented by a second degree equation. The regression curve of a parabola type is matched with the clinical judgment.


The high incidence and prevalence of chronic kidney disease (CKD) in Taiwan have produced tremendous burdens on health care resources. The work environment of air force special operations personnel engenders high psychological stress, and the resulting increased blood pressure can lead to glomerular hypertension and accelerated glomerular injury in the long term. The aim of the study was to establish the predictive models to define the predictors of CKD.The results indicated that the prevalence of CKD over 4 consecutive years was 3.8%, 9.4%, 9.0%, and 9.4%. The capability of using occult blood in urine to predict the risk of CKD after 1, 2, and 3 years was statistically significant. The age-adjusted odds ratio (OR) and 95% confidence interval (CI) were 7.94 (95% CI: 2.61–24.14), 12.35 (95% CI: 4.02–37.94) and 4.25 (95% CI: 1.32–13.70), respectively.The predictive power of occult blood in urine for the risk of CKD in each model was statistically significant. Future investigations can explore the feasibility of implementing simple and accurate urine dipsticks for preliminary testing besides annual aircrew physical examinations to facilitate early detection and treatment.This study was a longitudinal study, in which air force special operations personnel who received physical examinations at military hospitals between 2004 and 2010 were selected. CKD was determined based on the definition provided by the US National Kidney Foundation. Overall, 212 participants that could be followed continuously for 4 years were analyzed. Improvements in the medical care quality and dietary habit and lifestyle changes recently have led to the rising incidence and prevalence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. The high incidence and prevalence of ESRD in Taiwan is a concern requiring attention. The prevalence of early CKD is considerably higher than that of ESRD. CKD increases both all-cause mortality and medical expenditures . Thus, CCKD is the most prevalent chronic disease in Taiwan, accounting for 2.9% of the total mortality rate. The number of deaths related to this disease increased from the previous year . Once CKet al. conducted a large cohort study in Taiwan and found that the prevalence of stages 1 to 3 CKD was 11.6%, and the prevalence of stages 4 to 5 CKD was 0.3%. However, only 3.5% of the patients were aware that they had CKD [According to the results of the 2007 Follow-up Investigation on Hypertension, High Blood Glucose, and High Cholesterol in Taiwan by the Bureau of Health Promotion, the prevalence of CKD in Taiwan was 9.8% . In 2008The study included 212 aircrew members in the air force. Analysis was performed on the results from the fourth physical examination (from the most recent year). The average age was 40.4 ± 7.15 years. Average height was 173.23 ± 5.52 cm. Average weight was 75.30 ± 8.47 kg. Average systolic blood pressure was 127.51 ± 7.60 mmHg and average diastolic blood pressure was 79.67 ± 6.31 mmHg.P < .001) regarding the examination year.The results of 4 consecutive years of physical examinations from the valid sample of 212 aircrew members were analyzed and compared as shown in Table P < .05). Those possessing abnormal urine ketone levels were at 4.88 times higher risk of CKD at the third examination (P < .05). Those possessing occult blood in urine were at a higher risk of CKD at the second, third, and fourth examinations (P < .01). Those possessing abnormal levels of white blood cells in urine were at 12.47 times higher risk of CKD at the second examination (P < .01). After controlling for age, participants demonstrating abnormal urobilinogen levels continued to be at a higher risk of CKD at each examination compared to those possessing normal urobilinogen levels (P < .05).Logistic regression analysis Table  indicateThe examination indicators from a specific year were used as independent variables and the presence of CKD in the subsequent first, second, and third years was used as the dependent variable. Logistic regression analysis Tables  and 4 inAccording to the 2012 annual report from the US Renal Data System, the incidence of ESRD in Taiwan for 2010 was 361 per 1 million people, second to only the United States at 369 per 1 million people. However, the incidence has decreased gradually recently. The prevalence of ESRD in Taiwan was 2584 per 1 million people, which was the highest rate in the world . Dialysiet al. performed a large cohort study in Taiwan, and used the aMDRD formula to estimate the prevalence of CKD at 11.93%  [ESRD typically develops from CKD. Early CKD does not present clear symptoms, frequently resulting in delayed diagnosis and treatment. Therefore, highly sensitive, accurate, and ethnically appropriate screening methods should be established for the public and high-risk groups to facilitate early detection and treatment and to prevent the deterioration of renal function. Wen Past studies have indicated numerous causes of CKD, the most common being hypertension and diabetes –16. HypeCurrently, few studies have implemented long-term prediction analysis on the CKD risk factors for special populations. The importance of this study lies partly in verifying whether abnormal indicators in the health examinations of a particular year can be used to predict the risk of CKD in the subsequent first, second, and third years to enable early detection and treatment. The long-term prediction analysis indicated that occult blood in urine was statistically significant for predicting the risk of CKD in each model. The presence of red blood cells in the urine is referred to as occult blood in the urine. This is commonly used as a clinical indicator of kidney disease, such as kidney trauma, kidney stones, renal tumors, and acute nephritis. Although occult blood in urine does not indicate CKD directly, it is highly correlated with renal parenchymal damage . Future This study had some limitations. First, this study was unable to confirm whether the course of disease of renal parenchymal damage in early CKD, such as urine protein, positive occult blood in urine, or a urine pH value greater than 8, continued for more than 3 months. Second, air force aircrew members are screened rigorously because of the special operating environments of their work; only healthy personnel may continue to serve on missions. Therefore, cases of patients with stages 4 to 5 CKD were lacking. Consequently, caution is required when extrapolating the results of this study. Third, the physical examination data were generated by four hospitals, which may cause a batch effect in this study. However, the batch effect was small because all the aircrew members had the same protocol of physical examinations in Armed Forces General Hospital in Taiwan. Finally, since the requirements to aircrew members, who with diabetes or diseases will not be allowed to serve as an active aircrew, there were no participants who had been taking anti-hypertensive agents or anti-DM agents at the inclusion in the study. Furthermore, a significant drawback that hypertension is one of the most important factors leading to CKD. However, the contribution of hypertension to development of CKD could not be analyzed due to insufficient data (covering only 55 participants). We suggest a future work to follow up inactive aircrew members who with diseases that can incremental samples for investigating the contribution of hypertension to development of CKD.In addition to calculating the GFR, the presence of renal parenchymal damage must also be considered to determine early CKD. This study indicated that occult blood in urine, urobilinogen, white blood cells in urine, and urine ketones were predictors for the future risk of CKD. Thus, the feasibility of implementing simple and accurate dipsticks for preliminary testing outside of annual aircrew physical examinations can be investigated in subsequent studies, conforming to the principles of “early detection, early treatment, and continued tracking.” Moreover, the confidence interval is wide due to small sample size. The interpretation of the result of this present study should be conservative, and further studies will be needed to confirm this findings.This study was a longitudinal study.Physical examination data were collected from 1398 aircrew members who received aircrew physical examinations between 2004 and 2010 at the following 4 military hospitals (or their branches): Taoyuan Armed Forces General Hospital, Taichung Armed Forces General Hospital, Kaohsiung Armed Forces General Hospital, and Hualien Armed Forces General Hospital. The study design and subject recruitment have been described elsewhere . The datIn 2002, the National Kidney Foundation Kidney Disease Outcome Quality Initiative (NKF KOQI) has classified each stage of CKD based on GFR into 5 stages, defining the disease as follows [(1) Kidney damage for ≧3 months, as defined by structural or functional abnormalities of the kidney with or without decreased GFR, manifest by either: pathological abnormalities; or markers of kidney damage, including abnormalities in the composition of the blood or urine, or abnormalities in imaging tests.2 for ≧3 months, with or without kidney damage.(2) GFR < 60 mL/min/1.73 mIn addition, stages 1 and 2 CKD must include one of the following: positive urine protein, positive occult blood in urine, or a urine pH value greater than 8.et al. to calculate the GFR [Numerous studies have developed formulas for convenient assessment and estimation of renal function. These formulas typically use serum creatinine to calculate the GFR. Because serum creatinine differs among individuals, the rate must be adjusted according to sex, age, and race . This st the GFR .−1.154 × age−0.203 × 0.742  × 1.210 (if black). The unit is mL/min/1.73 m2.The aMDRD formula is as follows: estimated GFR = 186.3 × serum creatininep < 0.05 were considered statistically significant. Data were analyzed using the IBM SPSS Statistics version 22 (IBM® SPSS® Statistics 22).Descriptive results of continuous variables were expressed as mean (standard deviation), categorical variables were expressed as frequency (%). All statistical analyses were performed with one-way analysis of variance (ANOVA) and Chi-square tests. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the potential risk factor levels and CKD risk. All statistical tests were two-tailed, and values of


R = 0.666; p < 0.001), cystatin C , BNP , ADMA , oxLDL , 24-hour systolic  and mean  BP values, and left ventricular mass index  and negatively with estimated glomerular filtration rate . In children with CKD, TM strongly depended on kidney function parameters, oxLDL levels, and 24-hour systolic and mean BP values. Thrombomodulin seems to be a valuable marker of ED in CKD patients, correlating with CKD stage as well as oxidative stress, BP values, and LVMI.Endothelial dysfunction (ED) and oxidative stress are potential new pathomechanisms of cardiovascular diseases in patients with chronic kidney disease (CKD). The aim of the study was to assess the association between endothelial dysfunction, oxidative stress biomarkers, and cardiovascular risk factors in children with CKD. Serum oxidized LDL (oxLDL), protein carbonyl group, urea, creatinine, cystatin C, thrombomodulin, asymmetric dimethylarginine (ADMA), von Willebrand factor, brain natriuretic peptide (BNP), lipids, high sensitivity C-reactive protein, intercellular adhesion molecule-1 levels, and albuminuria were measured. Anthropometric, ambulatory blood pressure (BP) measurements and echocardiography were performed. The studied group consisted of 59 patients aged 0.7–18.6 (mean 11.1) years with stages 1 to 5 CKD. Thrombomodulin strongly correlated with creatinine ( Cardiovascular diseases are the most frequent cause of morbidity and mortality in patients with chronic kidney disease (CKD). The adult population with impaired renal function is characterized by high incidence of classical cardiovascular risk factors; however, this cannot explain the high prevalence of cardiovascular events in children with kidney function impairment. Therefore, other factors such as endothelial dysfunction (ED) and oxidative stress are considered. Initially, ED was studied in the most advanced stage of CKD  and a reduction in endothelial-dependent vasodilatation of the brachial artery was demonstrated. Recent studies supported the concept that ED is present at early stages of chronic kidney disease , 2.Endothelial cells play a key role in maintaining vascular homeostasis. They regulate vasodilatation, fibrinolysis, and thrombosis through the synthesis and release of substances such as nitric oxide, prostacyclin, thrombomodulin, and tissue plasminogen activator , 4. EndoNoninvasive methods for ED assessment include evaluation of shed endothelial surface layer components—soluble thrombomodulin (TM) and syndecan-1 . TM is aAsymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthetase, is the recognized mediator of endothelial injury . IntraveAnother endothelial injury marker is the von Willebrand factor, a glycoprotein produced by endothelial cells and megakaryocytes. vWF is a cofactor of thrombocyte adhesion to connective tissue collagen, thereby exerting prothrombotic action. In the ASCOT study, patients with hypertension (HT) and organ damage (OD) had significantly higher vWF concentrations than those with HT but without OD (137 versus 125 IU/dl). After 6 months of intensive treatment, there was a reduction in systolic blood pressure and a decrease in vWF concentration suggesting an improvement in endothelial function .Increased urinary albumin excretion is not only a symptom of kidney disease but also an exponent of generalized endothelial dysfunction and cardiovascular risk. Because of technical difficulties in obtaining daily urine collection, the albumin to creatinine ratio in the first urine volume is increasingly used in clinical trials. In the study conducted in Denmark by Borch-Johnsen et al., microalbuminuria (>0.65 mg/mmol) significantly increased the risk of ischemic heart disease regardless of other atherosclerosis risk factors .In patients with CKD, both increased reactive oxygen (ROS) and nitrogen radical (RNS) generation and decreased antioxidative potential have been shown –15. Low-The aim of the study was to assess the association between endothelial dysfunction and oxidative stress biomarkers and cardiovascular risk factors in children with chronic kidney disease.The prospective study was conducted between June 2008 and February 2011. The study was performed in accordance with the Declaration of Helsinki of 1975 for Human Research and approved by the Bioethical Committee (KBET/17/B/2006). The parents and patients were educated as to the objective and method of performing the study and gave their written informed consent.Patients aged 0–18 years with diagnosed chronic kidney disease and elevated thrombomodulin level (>5 ng/ml) were included.The exclusion criteria were lack of consent of the patient or parents, congenital heart defects or other primary heart diseases, acute infections during measurements, acute damage, or failure of other organs.2); group 4: dialyzed children].Blood samples for basic research were taken on routine admission for diagnostic check-up in all patients (fasting for 12 hours). Additionally, three samples  were collected and centrifuged and plasma and serum were frozen at −80°C. Biochemical analyses were performed, and urea, creatinine, cystatin C, TM, ADMA, brain natriuretic peptide (BNP), vWF, fibrinogen, and lipids were measured. Based on serum creatinine, estimated glomerular filtration rate (eGFR) with the Schwartz et al.  and FillTo assess endothelial dysfunction and oxidative stress, the concentration of TM, ADMA, vWF, and oxLDL particles and the concentration of carbonyl groups resulting from oxidation of proteins were used. Concentrations of serum thrombomodulin , high sensitive C-reactive protein (hsCRP) , oxLDL , protein carbonyl groups , intercellular adhesion molecule-1 (ICAM-1) , and vWF activity  were determined with ELISA. BNP concentrations were measured with the IRMA method .Anthropometric measurements of patients such as weight, height, and waist circumference were measured during each visit, and body mass index (BMI) was calculated. Ambulatory blood pressure measurements (ABPM) with SpaceLabs 90207 device and cuff of appropriate size were performed. Blood pressure (BP) measurements were performed every 20 minutes during the day and every 30 minutes during the night. Mean values of systolic (SBP), diastolic (DBP), and mean BP  were calculated. Hypertension was defined as BP values equal to or exceeding the 95th percentile for gender, age, and height. BP values were analyzed and expressed in standard deviations (SD).2.7 to normalize and linearize the relationship between LVM and height . Differences between the groups were compared using the Mann–Whitney We examined 59 patients (36 boys and 23 girls) aged 0.7 to 18.6 (mean 11.1) years with stages 1 to 5 CKD  who were under constant medical control in the University Children's Hospital in Krakow. Among diseases leading to the development of CKD in the examined children, the highest prevalence was noted in congenital abnormalities of the kidney and urinary tract (59%) and nephrotic syndrome.Patients were divided into 2 groups based on the thrombomodulin concentration. A cut-off point of double upper limit of normal (ULN) for elevated thrombomodulin was proposed. Clinical data and basic kidney function parameters depending on thrombomodulin concentration are presented in μmol/l; p < 0.05), BNP  versus 4.43 ; p < 0.05), and oxLDL  versus 80.6 ; p < 0.05) concentrations. The concentrations of vWF, carbonyl groups, hsCRP, ICAM-1, and fibrinogen did not vary significantly (p = 0.012) and MAP  versus 82.0 ; p = 0.022). There were no differences in other BP values , respectively, as shown in p < 0.001; p < 0.001; p = 0.003).Thrombomodulin concentrations increased with CKD stage , creatinine , and cystatin C  concentrations, eGFR calculated with Schwartz , and Filler formulas . Scatterplot presenting the correlation between cystatin C and thrombomodulin concentrations is shown in There was a significant correlation between thrombomodulin concentration and markers of renal function—urea , BNP , and oxLDL . Scatterplots presenting the correlations between ADMA, BNP, oxLDL, and thrombomodulin concentrations are shown in Figures 4R = 0.239; p = 0.082), carbonyl groups , hsCRP , and ICAM  concentrations have been found.Thrombomodulin concentration correlated significantly with other endothelial dysfunction and oxidative stress parameter concentrations: ADMA  and mean—MAP  BP values. Scatterplot presenting the correlation between mean 24-hour systolic BP values and thrombomodulin concentrations is shown in Thrombomodulin correlated significantly with 24-hour systolic . Scatterplot presenting the correlation between LVMI and thrombomodulin concentrations is shown in In the studied children with CKD, a significant correlation between thrombomodulin level and LVMI was found  which could indicate that thrombomodulin determines vascular injury and advanced calcification in patients with impaired renal function .The role of thrombomodulin as a vasoprotective agent may also be confirmed by the results of Eguchi et al., who have shown that the supply of recombinant TM reverses FK506-induced ED. Recombinant TM is registered in Japan for DIC treatment .Our study showed a significant correlation between the marker of endothelial dysfunction and a recognized oxidative stress marker—oxLDL. Significant increases in oxLDL levels have been also found in children with markedly increased thrombomodulin levels, which may indicate an intensification of both ED and oxidative stress processes with increasing renal function impairment.Holvoet and coauthors suggested to measure the concentration of circulating oxidized LDL for a more accurate assessment of cardiovascular risk. Patients with coronary artery disease confirmed in angiography had significantly higher oxLDL levels. There was also a significant correlation between oxLDL and most of the Framingham risk factors .In the studied group, the protein carbonyl content did not increase in the patients with higher thrombomodulin levels. In our previous study, the protein carbonyl content did not increase in advanced stages of CKD .In children, there are currently no studies evaluating TM levels in chronic kidney disease, but endothelial dysfunction has been widely described in nephrotic syndrome. In the study by Tkaczyk et al. and Sharma et al., children with active disease had significantly higher thrombomodulin concentrations compared to control group , 34.In the studied group of children with chronic kidney disease, thrombomodulin correlated significantly with another mediator of endothelial injury—ADMA. ADMA meets multiple uremic toxin criteria—it is a product of protein metabolism, is accumulating in renal failure, is removed during dialysis, and has a specific mechanism of action. In kidney disease, not only ADMA excretion in the urine but also its metabolism (by enzymatic decomposition—dimethylarginine dimethylaminohydrolase) in kidney tissue is reduced.μmol/l) were found [μmol/l). The authors emphasized the fact that ADMA increased in the early stage of diabetic renal disease, that is, at GFR < 76 ml/min/1.73 m2.In the group of 600 patients with long-term type 1 diabetes (mean duration of 28 years), statistically significant differences in ADMA between patients with diabetic nephropathy and normoalbuminuria  has been demonstrated. Albuminuria is a recognized cardiovascular risk factor and an indicator of renal failure . In the The acquired results—significantly higher systolic and mean blood pressure values in patients with higher thrombomodulin levels—prove the well-known influence of hypertension on endothelial damage.Endothelial dysfunction has been proposed as one of the main mechanisms contributing to the association of chronic kidney and cardiovascular disease. In CKD oxidative stress, subclinical chronic inflammation and uremic toxins are responsible for endothelial cell injury . The potThe lack of correlation between TM and other ED biomarkers  may be the result of the small study group.In children with chronic kidney disease, thrombomodulin seems to be a valuable marker of endothelial dysfunction, correlating strongly with CKD stage, kidney function parameters , as well as oxidative stress, hypertension, and left ventricular hypertrophy.


Bedside non-invasive techniques, such as radial artery tonometry, to estimate hemodynamic parameters have gained increased relevance as an attractive alternative and efficient method to measure hemodynamics in outpatient departments. For our pilot study, we sought to compare cardiac output (CO), and stroke volume (SV) estimated from a radial artery tonometry blood pressure pulse analyzer (BPPA)  to pulsed-wave Doppler (PWD) echocardiography derived parameters.2). All patients had pre-operative transthoracic echocardiography (TTE). We measured the hemodynamic parameters with the BPPA from the radial artery, randomly before or after TTE. For the comparison between the measurement methods we used the Bland-Altman test and Pearson correlation.From January 2015 to December 2016, all patients scheduled for coronary artery bypass (CABG) surgery at our department were screened. Exclusion criteria were, inter alia, moderate to severe aortic- or Mitral valve disease and peripheral arterial disease (PAD) > stage II. One hundred and seven patients were included . The mean TTE-SV was 71.3 ± 16.2 mL and the mean BPPA-SV was 73.8 ± 19.2 mL. SV measurements correlated very well between the two methods . The Bland-Altman analysis for SV revealed a bias of −2.54 mL and SD of ±8.42 mL and upper and lower limits of agreement of −19.05 and +13.96 mL, respectively.Mean TTE-CO was 5.1 ± 0.96 L/min, and the mean BPPA-CO was 5.2 ± 0.85 L/min. The Bland-Altman analysis for CO revealed a bias of −0.13 L/min and SD of 0.90 L/min with upper and lower limits of agreement of −1.91 and +1.64 L/min. The correlation of CO measurements between DMP-life and TTE was poor (Our study shows for the first time that the DMP-life tonometry device measures SV and CO with reasonable accuracy and precision of agreement compared with TTE in preoperative cardiothoracic surgery patients. Tonometry BPPA are relatively quick and simple measuring devices, which facilitate the collection of cardiac and hemodynamic information. Further studies with a larger number of patients and with repeated measurements are in progress to test the reliability and repeatability of DMP-Life system. Hemodynamic monitoring is crucial, not only during anesthesia and in intensive care units (ICU) but also in the normal ward and in the follow-up during outpatient visits, especially in cardiac surgery patients. The main goal of hemodynamic monitoring is to ensure a sufficient end organ perfusion and oxygen delivery by optimizing stroke volume (SV) and cardiac output (CO). The gold standard in monitoring CO and SV is still the pulmonary artery catheter (PAC), its invasive nature and life-threatening complications largely restrict its use in the operating room and in the ICU . During Our study was conducted in the cardio-surgical department of a German university hospital . The ethics committee (Ethikkommission der RWTH Aachen) approved the study (EK 151/90). Written informed consent was obtained from all patients prior to study enrolment.Between January 2015 and December 2016, all patients who were planned for nonemergency coronary artery bypass graft (CABG) surgery, were screened. Exclusion criteria were: (1) peripheral artery disease (PAD) more than Fontaine grade II, (2) moderate to severe aortic stenosis or regurgitation, (3) moderate to severe mitral stenosis or regurgitation, (4) atrial fibrillation, (5) left ventricular ejection fraction <40%, (6) no accurate ultrasound window for TTE. Five hundred and seventy-two patients were screened and 107 patients were included in the study . Patient® Vingmed-General Electrics, Horten, Norway), and data analysis was performed offline using the Echopac system. TTE were performed according to the American society of echocardiography and European association for echocardiography (ASE/EAE) guidelines  of the LVOT from the parasternal window was used to calculate the cross-sectional area (CSA) (CSALV OT = (d∕2)2 × π); (2) the velocity time integral (VTI) measured at the same site (LVOTV TI) at the apical three-chamber view with pulsed-wave Doppler. SV averaged over five consecutive beats was used to compute the CO (SV × heart rate).TTE derived SV was then calculated using the pulsed Doppler (PW) through the left ventricular outflow tract (LVOT) as a product of the velocity time integral through the LVOT and the cross-sectional area of the LVOT as described by The pulse was measured by radial artery tonometry device DMP-Life . With the array pressure sensor equipment, tonometry devices have improved to confirm blood vessels’ position accurately and also improved reproducibility and reliability. Through orthogonal applanation to radial artery, tonometry devices can get signals, which include blood pressure, skin condition, blood vessel stiffness and hemodynamic condition .The sensor module of DMP-Life is equipped with multi-channel array with five piezoresistive semiconductor transducers  and prec2, but for each patient, individual maximum applied pressure can vary according to patient’s pulse pressure response. Waveforms at each applying pressure can be used to analyze the elasticity and stiffness of the vascular system. The concept of pulse pressure (systolic blood pressure minus the diastolic pressure) is applied to the tonometric sensor.The range of the applied pressure in DMP-Life system is set at 0∼400 g f/cm2 is applied, and in 2 was applied. The response of the pulse to the applied pressure result in a typical shape for each patient. Sharp end or arrow shape or triangle shape may appear in healthy elastic vessel , diastolic blood pressure (DBP), pulse pressure (PP), pulse rate (PR), radial-augmented index (R-AI), stroke Volume (SV), stroke volume index (SVI), cardiac output (CO), cardiac index (CI), systemic circulation resistance index (SCRI) and pulse conditions. For this pilot study, we used only SV and CO.a + b × (T4 + c) + d × PR + e × PP + f × BSA + g × Age; and CO = SV × PR, where, T4: LV (sec); PR: Pulse rate (beat/min); PP: Pulse Pressure (mmHg); BSA: Body surface area (m2); a, b, c, d, e, f and g: coefficient constants. DMP-life has tonometric blood pressure measure function and does not need calibration with other blood pressure monitor.DMP-Life uses a modified systolic area with Kouchoukos correction algorithm  to calcuBefore performing the measurement with DMP-Life, patients should take at least 5 min of rest time. Patients were in lying supine position. After entering the patient’s biometric data , the physician then first felt the radial artery pulse and chose the best position. A bracelet with the pressure sensor cartridge (DMP-life) was placed on the patient’s wrist over the radial artery . The senThe DMP-life system’s monitor displays inter alia CO and SV values derived from pulse contour analysis using a proprietary auto-calibrating algorithm, as mentioned above .Continuous variables are presented as mean ± standard deviation (SD) or as median (25th and 75th percentile), where appropriate. Categorical variables are described in absolute numbers and percentages. We computed the mean of the differences (=bias) between BPPA- and TTE-CO/SV, the SD, and the 95% limits of agreement (=bias ±1.96 × SD) to describe the agreement between BPPA (DMP-life) and TTE measurements, Bland–Altman plots for repeated measures were also calculated . The PeaOne hundred and seven patients were included in the study. The mean age was 66.1 ± 9.9 years and 14.1% were female. Clinical characteristics of the patients are demonstrated in At the time of performing the measurements with TTE and DMP-life, the mean systolic blood pressure was 136.9 ± 11.6 mmHg, mean diastolic blood pressure was 82.2 ± 6.2 mmHg and the heart rate was 71.8 ± 15.1/min.A total of 107 matched SV and CO data points were available for the final statistical analysis.r = 0.900, p < 0.0001) and the r squared (r2) for the goodness of fit was 0.811   .Our study shows for the first time that the DMP-life technology measures SV and CO with reasonable accuracy and precision of agreement compared with TTE in preoperative cardiothoracic surgery patients. Our findings are promising as there is a clear trend toward non-invasive hemodynamic monitoring . The biar = 0.842, p < 0.0001). r = 0.85; p < 0.0001). Our findings are in line with On the contrary, CO correlation was poor. As CO is calculated from SV and heart rate, this discordance can only be explained by a variation in patient’s heart rate. As TTE and DMP-life were not performed simultaneously, variation in the heart rate was present in all patients, explaining this result. PAC is still used as the reference method to monitor hemodynamics and to validate alternative monitoring systems , but its® transpulmonary thermodilution or with PAC in 49 critically ill medical ICU patients and they concluded that radial artery applanation tonometry is not suitable to determine CO in critically ill hemodynamically unstable patients.On the other hand Arterial tonometry is a non-invasive method for blood pressure measurement and it provides complete pulse pressure waveform, which in turn has implications in several disease diagnoses .A typical arterial tonometer consists of a plunger and pressure sensor placed at the centre of a superficial artery. The plunger is used for arterial flattening via the application of hold down pressure. A pressure sensor is used to measure contact stresses at the surface above the radial artery at optimal level of flattening . DiffereThe DMP-Life pressure pulse analyzer is a relatively quick and simple measuring method, which facilitates the collection of cardiac and hemodynamic information. Since the tonometry technique of estimating the CO and SV is relatively accurate, it seems to be a good tool for patients with cardiac disease who need continuous self-monitoring.Our study is limited by the usual shortcomings of a small cohort single-center study and a probably heterogeneous patient group. In our proof of concept study, we did not use PAC as invasive method to compare CO and SV estimated from DMP-Life, which may limit the interpretation of the accuracy of DMP-life measurements, on the other hand, TTE measurements have been validated against PAC based values. A major issue related with the accuracy of CO/SV measurements is the reproducibility of the measurement, which was not assessed in our study and no repeated measurements in pre-, peri- and postoperative period were performed to determine whether DMP-Life detect changes in CO precisely. Another important issue was that measurements with DMP-life and TTE were not performed simultaneously, which did result in a poor correlation of CO, most likely due to different inter-individual heart rate at the time of performing the measurements.One of the limitation of tonometry method is that the signal is very position sensitive, the transducer needs to be positioned directly over the center of the artery. This has been dealt with by using an array of five piezoresistive transducers placed across the artery.Our study demonstrates for the first time that the DMP-life tonometry device measures SV and CO with reasonable accuracy and precision of agreement compared with TTE in preoperative cardiothoracic surgery patients. Tonometry BPPAs are relatively quick and simple measuring devices, which facilitates the collection of hemodynamic information. Further studies with a larger number of patients with repeated measurements are in progress to test the reliability and repeatability of DMP-Life system measurements.10.7717/peerj.4132/supp-1Data S1Click here for additional data file.


We aimed to study the integrative physiological responses to a 3-day strict DI protocol in 12 healthy men, and to assess the extent of multi-system deconditioning. We recorded general clinical data, biological data and evaluated body fluid changes. Cardiovascular deconditioning was evaluated using orthostatic tolerance tests (Lower Body Negative Pressure + tilt and progressive tilt). Metabolic state was tested with oral glucose tolerance test. Muscular deconditioning was assessed via muscle tone measurement.Dry immersion (DI) is a Russian-developed, ground-based model to study the physiological effects of microgravity. It accurately reproduces environmental conditions of weightlessness, such as enhanced physical inactivity, suppression of hydrostatic pressure and supportlessness. Results: Orthostatic tolerance time dropped from 27 ± 1 to 9 ± 2 min after DI. Significant impairment in glucose tolerance was observed. Net insulin response increased by 72 ± 23% on the third day of DI compared to baseline. Global leg muscle tone was approximately 10% reduced under immersion. Day-night changes in temperature, heart rate and blood pressure were preserved on the third day of DI. Day-night variations of urinary K+ diminished, beginning at the second day of immersion, while 24-h K+ excretion remained stable throughout. Urinary cortisol and melatonin metabolite increased with DI, although within normal limits. A positive correlation was observed between lumbar pain intensity, estimated on the second day of DI, and mean 24-h urinary cortisol under DI. In conclusion, DI represents an accurate and rapid model of gravitational deconditioning. The extent of glucose tolerance impairment may be linked to constant enhanced muscle inactivity. Muscle tone reduction may reflect the reaction of postural muscles to withdrawal of support. Relatively modest increases in cortisol suggest that DI induces a moderate stress effect. In prospect, this advanced ground-based model is extremely suited to test countermeasures for microgravity-induced deconditioning and physical inactivity-related pathologies. Spaceflight induces physiological multi-system deconditioning which may impact astronauts efficiency and create difficulties upon their return to normal gravity , and diet was the same for all participants and standardized to body weight in energy and nutrients. Daily caloric intake was approximately 2,820 kcal for baseline and recovery and 2,270 kcal for the immersion period. Daily intake for sodium and potassium was approximately 3–4 g. Daily nutrition is detailed in supplementary data , 3 days (72 h) of dry immersion  and 2 days of ambulatory recovery . Two subjects in two separate baths underwent DI simultaneously. Thermoneutral water temperature (32.5–33.5°C) was continuously maintained. Light-off period was set at 23:00–07:00. General discomfort and lumbar pain under immersion were evaluated using a visual analog scale. Daily hygiene, weighing and some specific measurements required extraction from the bath. During these short out-of-bath periods, subjects maintained the −6° head-down position. Total out-of-bath supine time for the 72 h of immersion was 4.7 ± 0.16 h. Otherwise, during DI, subjects remained immersed in a supine position for all activities and were continuously observed by video monitoring. Blood pressure, heart rate (HR) and tympanic body temperature were measured twice daily at 07:00 and 19:00. Body weight was measured daily at 07:00. Onset and end of immersion both occurred at 09:00, therefore morning measurements on DI1 were performed before immersion, and on day R0-still under immersion. Before, during and after DI, water intake was ta Table . The timThis 3-day DI allowed for several protocols on different domains performed by 8 research groups. Some studies have already been published to-date  was chosen as the accepted standard for measuring orthostatic tolerance  and standard ECG  were recorded continuously. Orthostatic tolerance time, heart rate (HR), blood pressure , stroke volume (SV), total peripheral resistance were estimated. Stroke volume and total peripheral resistance were evaluated from the blood pressure wave using the modelflow® method . The state of autonomic nervous system was estimated via power spectrum analysis of heart rate variability. Sympathetic index, an indicator of sympatho-vagal balance, was calculated as the ratio of low-to-high frequency spectral power. Spontaneous baroreflex sensitivity was estimated using online software (televasc.fr).Progressive tilt was used to progressively stimulate the cardiovascular system (volume receptors for low angles and baroreceptors for higher angles) and vestibular system. A head-up tilt test with progressive angles  was performed at baseline on B-3 and on the second recovery day . After 10 min of supine rest recording, the subject was tilted at 20° (5 min), 45° (5 min) and 80° (5 min), and then returned to the horizontal position.During the progressive tilt test, HR, systolic and diastolic blood pressure, total peripheral resistance, stroke volume, sympathetic index, spontaneous baroreflex sensitivity were calculated and recorded.Antecubital venous blood samples were collected before , during  and after DI . Blood sampling was performed in the morning before breakfast, except for DI1 when it was done in the evening (10h of DI).Plasma and serum samples were analyzed for electrolytes , glucose, proteins, albumin, urea, and creatinine concentrations, high-sensitivity CRP, insulin, leptin, triglycerides, total cholesterol, and HDL-cholesterol. LDL-cholesterol was calculated using the Friedewald formula. Homeostasis model assessment-insulin resistance index (HOMA-IR) was calculated as fasting insulin concentration (μU/mL) × fasting glucose concentration (mmol/L)/22.5.Additionally, on B-3 and R+1 blood count, GGT, ALT, AST, alkaline phosphatase, total bilirubin and prothrombin time were assessed. Hb, Hct, renin, aldosterone and blood natriuretic peptide (BNP) were assessed on B-3, R0 and R+1.Glucose tolerance tests were performed in the morning on B-1 and DI3 (48 h of immersion). Blood glucose and insulin were measured after an overnight fast before and 30, 60, 90, and 120 min after a 75-g glucose intake (consumption of glucose solution drink within 5 min).The total area under the blood glucose curve (AUC-Glu) and insulin curve (AUC-Ins) during the 75-g oral glucose tolerance test were calculated using the trapezoidal rule.+, K+), cortisol and 6-sulphatoxymelatonin .Urine pools were collected over 12 h (07:00–19:00 pool for “day” and 19:00–07:00 pool for “night”) throughout the protocol. Light on/off periods were not taken into account for urine collection, therefore “night” pools included 4 h of light-on (07:00–23:00) and 8 h of light-off (23:00–07:00). Urine volume was measured, and aliquots stored at −80°C. Partial water balance, defined as the difference between consumed water and urine volume, was calculated. Urine samples were analyzed for electrolytes . Plasma aldosterone was determined by a competition radioimmunoassay using a commercially available RIA kit . Urinary cortisol and aMT6s assays were carried out by radioimmunoassay. All other variables from blood and urine samples were evaluated using the Architect c16,000 automated clinical chemistry analyzer (Abbott). Minimal detectable levels for aldosterone and BNP were 10 ng/L, for hs-CRP–0.1 mg/L. Results that were less than the minimal detectable level, were taken for half minimal value.Blood volume and plasma volume were estimated using the optimized CO-rebreathing method  before (B-1), 6 h following onset (DI1) and on day 3 of immersion (DI3), and in recovery period on R0 (6 h following the end of DI) and on R+1.m. rectus femoris, m. tibialis anterior, m. gastrocnemius lateralis and m. soleus. Trunk measurements were taken on the right and left m. splenius, m. trapezius, m. longissimus cervicis, m. longissimus thoracis and lumbar portion of m. multifidus. Since trunk data showed no difference between the right and left sides , results from right and left sides were averaged. For technical reasons, the data of 2 subjects (subjects C and D) have not been analyzed.During the tests, the subject was out-of-water in a relaxed supine position . The testing end of the myotonometer was kept perpendicular to the muscle's projection in the middle of the muscle belly, at the same muscle point throughout the study. The device was used in multiscan mode, where one measurement corresponded to the mean of 5 mechanical taps. Leg measurements were taken on the left The values are presented as mean ± SEM. Statistical analysis was performed with Prism6 GraphPad. Data were compared by a one-way and two-way repeated measures ANOVA followed by post hoc Bonferroni test. Relationships between data were examined using the Pearson correlation coefficient (r). Detailed correlations are given in supplemental data Table .HR, blood pressure and body temperature remained within normal limits throughout the protocol. Baseline values of blood pressure and temperature were slightly higher in the evening. On the third day of immersion HR, blood pressure and body temperature did not differ significantly from B-1 baseline level Figure . Body wead libitum was decreased as anticipated on DI1, due to the known reset of water balance to lower level , while total Hb mass diminished by 3% . In relation to plasma volume, the CO technique showed a 16 ± 2% decrease at DI3 compared to DI1, and the Dill and Costill estimation showed a 14 ± 2% decrease vs. B-3. Hence, there was no significant difference between these two types of measurements. There were no changes in plasma volume at R+1 compared to baseline. Pre-immersion plasma volume expressed in ml/kg correlated with initial r = 0.67; p = 0.017), and percent reduction in plasma volume also correlated with initial r = −0.76; p = 0.006), i.e., fitter subjects had greater relative plasma volume at baseline and greater hypovolemia under DI.Blood volume decreased by 11% on R0 . Twenty-four hours after DI3, renin was expectedly increased by two-fold, and aldosterone by 3-fold. Brain Natriuretic Peptide (BNP) was below the minimum detectable level in all subjects on DI3 and R+1 compared to 8.3 ± 1.6 ng/L on B-3 before DI .Presyncopal LBNP-tilt test revealed a pronounced decrease in orthostatic tolerance with orthostatic tolerance time drop from 27 ± 1 min–on baseline to 9 ± 2 min–on R0. Before DI all subjects tolerated the first stage of test which consisted of an 80° tilt for 15 min. However, immediately after DI, 9 subjects out of 12 were unable to accomplish this tilt. Therefore, orthostatic tolerance time for non-finishers averaged at 4.95 ± 0.7 min. No significant correlation between percent decrease in plasma volume and post-immersion orthostatic tolerance time was found .Upright measurements showed a decrease in systolic blood pressure, stroke volume and baroreflex sensitivity, accompanied by pronounced tachycardia on R0. Total peripheral resistance and sympathetic index, which were already increased in supine, failed to further increase with orthostasis. On R+1, upright position was still accompanied by greater tachycardia. Interestingly, while tilt-induced sympathetic activation before DI increased progressively with verticalisation [reaching maximum at maximal angle of tilt (80°)], on R+1 the maximal sympathetic index was observed at 45°  was not significantly modified under immersion. Behavior of deep back muscle tone had cervico-lombar gradient. Tone immediately dropped in the upper part (12% for m. longissimus cervicis), shifting to slight decrease on D3 in the middle (m. longissimus thoracis) and was not modified in the lower part (lumbar portion of m. multifidus). Six hours following the end of DI, muscle tone was completely restored.Muscle tone variations under DI are shown in Figure + excretion were preserved . As well, we observed a positive correlation between mean discomfort level and mean 24-h urinary melatonin metabolite under DI (40.5 ± 5.4 μg/24 h) .In general, the majority of subjects described the discomfort level experienced under DI as 30–45 out of 100. Some subjects reported pronounced discomfort at nighttime. We observed important inter-subject variance in auto-reported discomfort level, varying from 0 to 88. There was no significant difference in discomfort level between the different days of DI. Eleven out of the 12 subjects reported moderate back pain under DI, which was predominantly localized in the lumbar area for 10 subjects. Lumbar pain intensity as estimated on DI2 was 3.8 ± 0.7 on the scale of 1–10. There was a positive correlation between lumbar pain intensity and mean 24-h urinary cortisol during DI (199 ± 24 mmol/24 h) , 4/6 (67%)-after 14 days (p = 0.7), 5/9 (56%)-after 28, or 30 days (p = 0.35), and 4/7 (57%)-after 42 days of HDBR (p = 0.4) -after 4 days (p = 0.01), after 1.5 days of DI–1 out of 6 (p = 0.02)       .Sympathetic neural control is extremely important in maintaining blood pressure homeostasis against gravity Mano, . In our r = 0.47; p = 0.12), suggesting involvement of additional factors into orthostatic intolerance.Total peripheral resistance is an integrative characteristic of overall resistance of peripheral vasculature in the systemic circulation. Insufficient vasoconstriction  to orthostatic stimuli is an acknowledged major factor for microgravity-induced orthostatic hypotension Zhang, . Astronar = −0.36; p = 0.26). Similarly, Shulzhenko et al. . The degree of hypovolemia develops within the first 24 h and is not greatly dependant on the duration of actual or simulated microgravity, whereas the degree of orthostatic intolerance tends to increase with extension of microgravity. Aside from a reduction in plasma volume, other mechanisms including increased lower limb venous capacitance .Increased blood glucose and dyslipidemia may compromise endothelial integrity and microvascular functions  cyclically change kidney sensitivity for the excretory commands, thus preparing increase in renal excretion for the period of expected potassium intake with meal  might reflect a change in its “predictive”/feedforward regulation by homeostatic system of CNS . Consequently, the 19:00–07:00 urine pool would contain more “daily” urine than before, so night kaliuresis would appear to be elevated. However, night melatonin was not decreased as expected in case of increased “contamination” of night urine with daily portion. This suggests another potential explanation—a certain disturbance in circadian regulation itself. The observed delayed changes in renal KA relatively modest increase in cortisol suggests quite a moderate physiological stress effect of DI. During immersion, the increase in urinary cortisol level was more evident at night. It may be related to the greater perception of the stress factors inherent to DI at night time. Interestingly, in the first hours of immersion, a drop in cortisol levels was observed. In part, this is likely due to the fact that short time immersion is quite comfortable and relaxing, which is why the method is employed in a spa setting  induces an accelerated model of cardiovascular deconditioning in response to microgravity. The “support unloading” induced by DI provides rapid and profound cardiovascular deconditioning. This is exemplified by increased plasma volume loss, orthostatic intolerance, pronounced autonomic changes, pronounced metabolic impairment, rapid and profound decreases in muscle tone, and influence on circadian rhythms. DI is tolerated well enough despite backache, and shows rather moderate stress effect. Such rapid, profound and quickly reversible gravitational deconditioning renders the strict DI model extremely significant to test countermeasures for microgravity-induced deconditioning and physical inactivity-related pathologies.Conception and design of the study: MC, NN, GG, and RM. Data acquisition and sample analysis: SD, LA, RM, VR, FL, LT, and RW. Analysis and interpretation of results, drafting and revising the article: All authors.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.


Arterial hypertension and chronic kidney disease (CKD) are intimately related. The control of blood pressure (BP) levels is strongly recommended in patients with CKD in order to protect the kidney against the accompanying elevation in global cardiovascular (CV) risk. Actually, the goal BP in patients with CKD involves attaining values <140/90 mmHg except if albuminuria is present. In this case, it is often recommended to attain values <130/80 mmHg, although some guidelines still recommend <140/90 mmHg. Strict BP control to values of systolic BP around 120 mmHg was recently shown to be safe in CKD according to data from the SPRINT trial, albeit more data confirming this benefit are required. Usually, combination therapy initiated with an angiotensin receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEi) and commonly followed by the addition of a calcium channel blocker and a diuretic is needed. Further studies are required as well as new drugs in particular after the positive data obtained from new oral anti-diabetic drugs. On the other hand, CKD is accompanied by a very significant increase in cardiovascular (CV) risk2. As a consequence, the treatment of arterial hypertension is simultaneously directed to promote renal and CV protection. It is widely accepted that suppression of the renin-angiotensin-aldosterone system (RAAS) through the use of an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) constitutes the first step of therapy in patients with CKD1.Clinical and epidemiological evidence has demonstrated the importance of blood pressure (BP) control in order to prevent the development and to reduce the progression of chronic kidney disease (CKD)3. Initially, the capacity of ACEi and ARB for the diminution and primary prevention of albuminuria in CKD, and particularly in type 2 diabetics, was investigated5. The changes in albuminuria together with the control of arterial hypertension were determinants for the improvement in renal outcomes3. However, recent data have also shown that in hypertensive CKD patients with low levels of albuminuria, the exclusive attainment of low BP goals is associated with an improvement in eGFR6. Thus, in CKD patients, the presence of albuminuria is considered in KDIGO and several other guidelines as the key point to recommend a stricter BP goal 8. A similar BP goal may be considered in patients with low or no level of albuminuria. In fact, the renal data of the SPRINT trial indicate that a SBP goal lower than 120 mmHg was safe and effective in a subgroup of patients with CKD9.Studies examining the effect that antihypertensives have on kidney function have typically involved early or pre-existing primary renal disease and/or diabetic nephropathy patients. These trials were devoted primarily to investigating the evolution of renal function during a short period of time and in relatively small samples that impeded our knowledge of the simultaneous effects on CV outcome11. In fact, patients developing end-stage renal disease (ESRD) and entering dialysis are a minority among the CKD population; one could also consider them to be survivors, as a large number of patients with CKD die from CV disease before ESRD develops. As can be seen in the article published by Leveyet al.12 with data from the USA, 4.9% of the total CKD population has an eGFR below 60 mL/minute/1.73 m2. This represents a very relevant number of patients with CKD in stages 3a, 3b, 4, and 5, but only 0.2% attain the stage12. These data are obtained from different surveys (NHANES) performed in the US, and since these are cross-sectional data it does not capture the fact that many patients die before reaching the terminal stages of CKD. Recently, we published a review13 showing that data from some clinical trials in the field of arterial hypertension have demonstrated that CV and renal protection can be attained simultaneously using the same therapy, mainly consisting of a renin-angiotensin-aldosterone system (RAAS) blocker, a calcium antagonist, and a diuretic, to which a statin is frequently added. These data indicate that early and aggressive control of hypertension and albuminuria is very important to simultaneously protect the CV and renal systems.Albuminuria, increased serum creatinine values, and a lower eGFR are considered by current arterial hypertension guidelines as significant CV risk factors that add to the already-high risk of pre-existing CV risk factors such as diabetes, cholesterol, and smoking15.Unfortunately, many patients attain the advanced stages of CKD, where RAAS blockade is often incomplete in a relevant percentage of patients, particularly in stages 3b and 4 of CKD, not tolerating high doses owing to the frequent development of hyperkalemia. The recent development of new potassium binders will contribute to facilitating the long-term maintenance of RAAS blockers, in particular mineralocorticoid receptor antagonists, while maintaining adequate serum potassium levels2. These effects influence intraglomerular pressure negatively through the facilitation of the pulsatile transmission of uncontrolled systemic BP16. The renoprotection provided by antihypertensive agents depends on their capacity to lower systemic BP, impeding the damage in the renal vasculature from the arteries to the renal microcirculation and to the glomeruli through their specific effects on renal hemodynamics16. Usually, the combination of more than two drugs is needed to attain an adequate control that depends on counteracting the three main factors intervening in the development and progression of hypertension.Different mechanisms play a key role in the development and maintenance of hypertension in CKD. The most important of them are volume overload, due to the difficulty in sodium and water handling, and activation of the RAAS and of the sympathetic nervous system17, the BP Control for Renoprotection in Patients with Nondiabetic Chronic Renal Disease (REIN-2) trial18, and the African American Study of Kidney Disease (AASK)19. A secondary analysis of the AASK trial reported that strict BP control in patients with albuminuria >0.22 g/g creatinine had fewer composite endpoints 20, confirming the adequacy of lower goal BP with albuminuria. Interestingly, a long-term combined analysis of the MDRD and AASK studies showed that strict BP control did not delay the onset of ESRD but did reduce the relative risk of death in patients with CKD  during long-term follow up21.The goal BP for CKD is commonly recommended to be below 140/90 mmHg, except when albuminuria is presented. The abandoning of the prior commonly recommended BP goal of <130/80 mmHg in patients with CKD was due to the failure of randomized controlled trials (RCTs) devoted to investigating strict BP control in CKD to show benefit, particularly the Modification of Diet in Renal Disease (MDRD) study22. Interestingly, increased renal risk was observed with SBP values of <110 mmHg; this is in line with the potential negative effects on the kidney caused by a significant drop in renal perfusion pressure after the consequences of a maintained elevation of BP and the development of nephrosclerosis have taken their toll on the renal vasculature23. Other data related to mortality in patients with CKD indicate that the optimal BP differs and oscillates between 130 and 159/70 and 89 mmHg24. The progression of diabetic and non-diabetic renal disease was more effectively slowed down, and survival was also improved, when patients were administered an antihypertensive regime that included an ACEi or an ARB compared to a regime without; this observation was independent of attained BP25. On the other hand, dual blockade of the RAAS using ACEi plus ARB simultaneously did not show benefits in large-scale trials28. In the same way, the addition of the direct renin inhibitor aliskiren to standard therapy with a RAAS blocker in high CV risk patients with diabetes is not supported and may even be harmful28. As a consequence, combined use of the two RAAS blockers in patients with CKD has been discarded by guidelines29.On the other hand, data published as a meta-analysis of 11 randomized controlled trials in non-diabetic renal disease patients demonstrated that an SBP of 110–129 mmHg was associated with a lower risk for progressive renal disease30 indicate that strict BP control (SBP <120 mmHg) did not improve renal outcomes of type 2 diabetic patients, and according to several reports the SBP goal of <130 mmHg remains adequate in this condition for renal and CV protection31.Data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study32. It is well known that aldosterone antagonists reduce albuminuria in patients with CKD, on top of a RAAS blocker, by an amount of 30–40%35. As previously mentioned, a limiting factor for the wide use of aldosterone antagonists is linked with the risk of inducing hyperkalemia, which becomes a prominent concern as renal function deteriorates. Finerenone is a novel nonsteroidal mineralocorticoid receptor antagonist (MRA) that has greater receptor selectivity than spironolactone and eplerenone, can significantly decrease albuminuria in diabetic nephropathy, and has a much lower prevalence of hyperkalemia36. Actually, two seminal studies are ongoing to test the capacity of the new MRA finerenone to slow down the progression of diabetic nephropathy (NCT02540993)37 and to protect the CV system in type 2 diabetic patients (NCT02545049)38. The use of the new potassium binder patiromer and the selective cation exchanger sodium zirconium cyclosilicate15 will contribute to the facilitation of MRA use in patients with CKD.Aldosterone is a relevant mediator of progressive renal and CV damage39 and renal disease42 have been published, enhancing the need for an adequate intake of sodium in patients with CKD. A low-sodium diet contributes to the reduction of albuminuria by itself and through the enhancement of RAAS blockade41. On the other hand, there are drugs other than hypertensives that can positively influence renal function together with BP control, such as statins43, fibrates44, thiazolidinediones45, and antiplatelet therapy46. Treatments such as allopurinol47 and vitamin D supplementation48 require further investigation.Recently, new data on the role of sodium intake in the progression of CV disease49. Moreover, the analysis of secondary end points of the EMPA-REG trial showed that empagliflozin was associated with a slower progression of CKD50. These good results were partially due to the antihypertensive and natriuretic capacities of the drugs51.Recently, the results of the EMPA-REG trial showed a lower rate of CV death, total death, and heart failure in type 2 diabetic patients with the addition of empagliflozin to standard care52 and semaglutide53 have also shown a significant improvement in CV outcomes of type 2 diabetics that was accompanied by a more significant decrease in body weight and a less important drop in BP in the absence of natriuretic effects. This last point could explain the absence of effects on heart failure. Liraglutide also exhibited a renal protective capacity through a significant decrease in albuminuria52. Further studies will be presented in the near future with these two classes of drugs and will contribute to the reconsideration of type 2 diabetes treatment with regard to CV and renal protection.Results obtained with GLP-1 agonists liraglutideIn summary, strict BP control, adequate suppression of the RAAS, and an integrated approach to protection of the increased global CV risk are required to prevent the appearance and progression of CKD and simultaneously of CV disease. New drugs are coming that could facilitate the control of BP and improve both renal and CV outcomes.


To determine whether insomnia at baseline is a risk factor for new-onset asthma.We recruited 48 871 patients with insomnia (insomnia group) newly diagnosed between 2002 and 2007, and 97 742 matched controls without insomnia (control group) from Taiwan’s Longitudinal Health Insurance Database 2000. All of the patients were followed up for 4 years to see whether new-onset asthma developed. Patients with previous asthma or insomnia were excluded. The Poisson regression was used to estimate the incidence rate ratios (IRRs) and 95% CIs of asthma. Cox proportional hazard regression was used to calculate the risk of asthma between the two groups.After a 4-year follow-up, 424 patients in the insomnia group and 409 in the control group developed asthma. The incidence rate of asthma was significantly higher in the insomnia group (22.01vs10.57 per 10 000 person-years). Patients with insomnia have a higher risk of developing new-onset asthma during the 4-year follow-up . The difference remained significant after adjustment .This large population-based study suggests that insomnia at baseline is a risk factor for developing asthma. The National Health Insurance Research Database (NHIRD) does not contain patient information before 1996.NHIRD does not include results of pulmonary function tests or blood tests for inflammatory cytokines, severity levels or the actual duration of insomnia.NHIRD does not include some important confounding factors, such as exposure to house dust mites, smoking habits, body mass index, family history or medical compliance.Methodology strengths of this study is the large sample size and long-term follow-up which provide considerable statistical power.This study can reflect the real-world situation in Taiwan and is more generalisable than are hospital-based or city-based databases.Insomnia is a sleep disorder that makes falling asleep or staying asleep difficult or prevents people who awaken early in the morning from returning to sleep at least three nights per week for at least 3 months, despite an adequate opportunity for sleep.et alAsthma is a heterogeneous disease characterised by recurrent attacks of breathlessness and wheezing caused by chronic airway inflammation.Taiwan launched a single-payer National Health Insurance (NHI) programme on 1 March 1995. The NHI databases, one of the largest and most complete population-based datasets in the world, include medical claims information on almost the entire population in Taiwan (>98% in 2009). The data used in this study were taken from the Longitudinal Health Insurance Database 2000 (LHID2000), which contains all claims data from 1996 to 2011 of 1 million  representative beneficiaries randomly selected from Taiwan’s National Health Insurance Research Database (NHIRD) in 2000. The LHID2000 provides encrypted patient identification numbers, sex, date of birth, dates of admission and discharge, the International Classification of Diseases, Ninth Revision—Clinical Modification (ICD-9-CM) codes of diagnoses and procedures, details of prescriptions and expenditure amounts for all outpatient and inpatient medical benefit claims. The institutional review board of Chi Mei Medical Center approved the study and waived the requirement of informed consent because the datasets analysed contained only deidentified patient information.We did a prospective cohort study with two study groups: the insomnia group (patients with newly diagnosed insomnia from 2002 to 2007) and an age-matched, sex-matched and index date-matched control group (patients without insomnia). Patients in the insomnia group  were diagnosed with insomnia during at least one inpatient hospitalisation or more than three times during outpatient clinic visits within 1 year as previous studies.The flowchart of study subjects selection presented in The diagnoses of different physical and mental conditions were based on ICD-9-CM codes during at least one inpatient hospitalisation or more than three times during outpatient clinic visits within 1 year before index date. Comorbidities were as follow: hypertension , depression , anxiety , allergic rhinitis (477.x), urticaria (708.x), atopic dermatitis (691.x), bronchiolitis , sleep apnoea , cardiovascular disease (stroke and coronary heart disease) .2 test was used to compare differences in the baseline characteristics and comorbid medical disorders between the insomnia and control cohorts. The incidence rate was calculated as the number of asthma cases during the follow-up, divided by the total person-years for each group. Poisson regression was used to estimate the incidence rate ratios (IRRs) and 95% CIs of asthma between the two groups. A Kaplan-Meier analysis of the cumulative incidence rates of asthma was plotted to describe the proportion of patients with asthma, and the log-rank test was used to analyse the differences between the two cohorts. In addition, Cox proportional hazard regression was used to calculate the risk of asthma between patients with and without insomnia during the follow-up period. SAS V.9.4 was used for all statistical analyses. Significance was set at P<0.05 (two sided). The detectable HR of 1.02 between insomnia group and compared controls was estimated at 90% statistical power and the probability of type I error at 0.05.Pearson’s χThe insomnia group contained 48 871 patients and the control group contained 97 742 . InsomniAfter a 4-year follow-up, 424 patients in the insomnia group and 409 patients in the control group had developed asthma. The incidence rate of asthma was significantly higher in the insomnia group  . PatientThis is the largest cohort study focused on the association between insomnia and new-onset asthma, and the first one on an Asian population. We found that patients with insomnia who sought medical assistance had a significant risk for developing asthma within 4 years of asking for treatment. In this study, the incidence of asthma in control group was 10.57 per 10 000 person-years. This finding is similar to the most recent epidemiology studyet alet alSivertsen Although our findings and those of other studiesThe strengths of our study are its prospective cohort design and that we used the LHID2000, a subset of Taiwan’s NHIRD, which contains physician-provided clinical diagnoses instead of illnesses self-reported by patients. The LHID2000 reflects the real-world situation in Taiwan and is more generalisable than are hospital-based or city-based databases. The large sample size and long-term follow-up also provide considerable statistical power.Our study also has some limitations. First, the NHIRD does not include results of pulmonary function tests or blood tests for inflammatory cytokines, severity levels or the actual duration of insomnia, some important confounding factors, such as exposure to house dust mites, smoking habits, body mass index, family history or medical compliance. Second, we did not assess the association between the medication for insomnia and asthma. However, it would be interesting to note if there were any differences in the development of asthma in those patients with insomnia who were treated versus those who were not. Further study is warranted to investigate the drug effect. Third, some patients might have minor asthmatic symptoms and have not been diagnosed yet before insomnia. Forth, sampling bias, such as a higher number of individuals likely to seek medical care among insomnia group than control group is possible and it may confound the analysis. Finally, because the NHIRD does not contain patient information before 1996, some of our patients might have been misclassified if they were diagnosed with asthma or insomnia before that year.We found that patients with insomnia who required medical assistance had a higher risk for developing new-onset asthma. Proper treatments for patients with insomnia might help prevent the progress of airway inflammation. Additional study is needed to identify the actual mechanism that connects insomnia and asthma.


Despite increased interest in non-invasive arterial pressure monitoring, the majority of commercially available technologies have failed to satisfy the limits established for the validation of automatic arterial pressure monitoring by the Association for the Advancement of Medical Instrumentation (AAMI). According to the ANSI/AAMI/ISO 81060–2:2013 standards, the group-average accuracy and precision are defined as acceptable if bias is not greater than 5 mmHg and standard deviation is not greater than 8 mmHg. In this study, these standards are used to evaluate the CareTaker® (CT) device, a device measuring continuous non-invasive blood pressure via a pulse contour algorithm called Pulse Decomposition Analysis.A convenience sample of 24 patients scheduled for major abdominal surgery were consented to participate in this IRB approved pilot study. Each patient was monitored with a radial arterial catheter and CT using a finger cuff applied to the contralateral thumb. Hemodynamic variables were measured and analyzed from both devices for the first thirty minutes of the surgical procedure including the induction of anesthesia. The mean arterial pressure (MAP), systolic and diastolic blood pressures continuously collected from the arterial catheter and CT were compared. Pearson correlation coefficients were calculated between arterial catheter and CT blood pressure measurements, a Bland-Altman analysis, and polar and 4Q plots were created.p < 0.0001 for all the comparisons). The Bland-Altman comparison yielded a bias  of −0.57, −2.52, 1.01 mmHg for systolic, diastolic, and mean arterial pressures, respectively with a standard deviation of 7.34, 6.47, 5.33 mmHg for systolic, diastolic, and mean arterial pressures, respectively . The polar plot indicates little bias between the two methods  with only a small percentage of points outside these lines. The 4Q plot indicates good concordance and no bias between the methods.The correlation of systolic, diastolic, and mean arterial pressures were 0.92, 0.86, 0.91, respectively (In this study, blood pressure measured using the non-invasive CT device was shown to correlate well with the arterial catheter measurements. Larger studies are needed to confirm these results in more varied settings. Most patients exhibited very good agreement between methods. Results were well within the limits established for the validation of automatic arterial pressure monitoring by the AAMI. Accurate real-time continuous non-invasive blood pressure monitors (cNIBP) can bridge the gap between invasive arterial pressure monitoring and intermittent non-invasive sphygmomanometry. Latest developments in this field promise accuracy and the potential to lower risk and improve patient outcomes. However, a recent systematic review and meta-analysis of 28 studies using non-invasive technologies by Kim et al. reported that all failed to satisfy the limits that have been established for the validation of automatic arterial pressure monitoring by the Association for the Advancement of Medical Instrumentation (AAMI) . AccordiWe evaluated the CareTaker® (CT) device  which has been described in detail elsewhere . BrieflyThe CT measures continuous noninvasive blood pressure via a pulse contour analysis algorithm called Pulse Decomposition Analysis (PDA) . It is bQuantification and validation of physiological parameters is accomplished by extracting pertinent component pulse parameters . Since tThe aim of the present study was to specifically compare the non-invasive arterial pressure values obtained with the CT to the reference invasive arterial pressure technique.The Cooper Health System Institutional Review Board approved the study, and all subjects gave informed written consent. Data from twenty-four adult patients requiring hemodynamic monitoring during major open abdominal surgery were analyzed in this study. Patients were not excluded due to other medical conditions.Measurements were obtained during general anesthesia in these patients starting with induction. The induction of anesthesia was chosen because the blood pressure fluctuations and variability typically found during this period provided an opportunity to compare tracking accuracy under baseline and induced controlled dynamic conditions. The data was evaluated using the ANSI/AAMI/ISO 81060–2:2013-related standards of accuracy and precision [After a stable signal was recorded, patients were induced under general anesthesia by using propofol (2-4 mg/kg) and fentanyl 250ug. Tracheal intubation was facilitated by the administration of rocuronium (0.6 mg/kg). Mechanical ventilation was started using a volume controlled ventilator to maintain an adequate saturation and an end-tidal carbon dioxide of 35 mmHg. Inhalational anesthetic (Isoflurane) was added to maintain a BIS monitoring of 40–45. Vasoactive drugs were used to maintain a MAP greater than 60 mmHg based on the catheter value. Hemodynamic variables were measured from both devices for the entire procedure. The MAP, systolic and diastolic blood pressures were continuously collected from the arterial catheter and CT and averaged over 10 s periods for both devices.Standard arterial blood pressure monitoring was performed prior to the induction of anesthesia using a 20G intra-arterial catheter inserted in the radial artery under local anesthesia using ultra sound guidance. The catheter was connected to a disposable pressure transducer with standard low compliant tubing. The transducer was placed at heart level and zeroed to ambient pressure. The transducer data was digitized, processed and collected using the Datex-Ohmeda S/5 Collect system . For analysis, MAP, systolic and diastolic blood pressures were averaged over 10 s intervals.The arterial pressure pulse signal was continuously measured using the CT device. For this study the CT device was calibrated using the arterial line blood pressure, but calibration can also be based on non-invasive oscillometric or oscillometric/auscultatory measurements. A fifteen second window at the start of the 30 min overlap section was used to obtain an arterial stiffness reading averaged across 5 beats, which was then used to calculate the PDA parameters for the blood pressure conversions Fig. . With thArterial catheter data were visually inspected and sections of obvious catheter failure, characterized by either continuous or spurious nonsensical reading, were excluded. Sections contaminated by excessive motion artifact such that the peak detection algorithm was no longer able to identify heart beats were also excluded. In the case of the CT data, a custom signal/noise factor (SNF) was used to identify poor quality data sections which were excluded. The factor is based on the standard ratio of the variances of the physiological signal band to the noise band and obtained using Fourier spectral analysis over an 8-s window with 1 s overlap . The freAll comparisons between CT data and arterial catheter data were post-processed. For each patient, the first 30 min overlap section was used for the comparison. A stable overlap section was defined as having an SNF of at least 140 for the CT data and having stable a-line data, as described above. In a onetime procedure, a 15 s window at the start of the 30 min overlap section was used to obtain PDA pulse parameters averaged across 5 beats which were then used for the blood pressure conversions. Patient-specific PDA parameters, once established, were not changed for the matching procedure, irrespective of hemodynamic changes.Initially, the data were examined to ensure that each method did not depart significantly from the normal distribution using the Shapiro-Wilk test. Intra- and inter-patient differences were calculated using matched datasets. To compare the two methods, Bland-Altman plots with corresponding correlation coefficients and Pitman test results were constructed for systolic, diastolic and the MAP. The 95% confidence intervals were calculated for each plot.http://www.scholarpedia.org/article/Signal-to-noise_ratio). Further comparison of the methods was done with a 4-Quadrant plot and polar plot. For the 4-Quadrant plot, differences in successive measurements for each device were plotted to compare the agreement in magnitude and direction of values [https://cran.r-project.org/).Because the estimation of the difference between the methods was the outcome of interest, no power analyses for sample size estimates were calculated prior to the study. Initial cohort size of 24 was therefore primarily driven by patient availability and the 81060 standard’s required lower limit of 15 patients when an a-line is used for comparison . The Bland-Altman comparison yielded a bias  of −0.57, −2.52, 1.01 mmHg for systolic, diastolic, and mean arterial pressures, respectively with a standard deviation of 7.34, 6.47, 5.33 mmHg for systolic, diastolic, and mean arterial pressures, respectively . The corresponding results for data collected during the entire procedure  including the 30-min study for MAP, systolic and diastolic were 0.87, 0.89, 0.82, respectively . Bland-Altman comparison for MAP, systole and diastole over the entire length of the procedures were SD 9.73, 13.13 and 10.23 mmHg, respectively .Patient characteristics are presented in Table To measure the trending agreement and bias between the CT and a-line data, 4-Quadrant and polar plots were calculated. The 4-Quadrant plot Fig.  displaysIn order to quantitatively assess the dynamic range of the comparison blood pressure data, the intra-patient maximum minus the minimum systolic and diastolic pressures from the a-line were compared for each 30 min comparison window. The mean ranges for systolic, diastolic and mean arterial blood pressures from all patients were 35.1 mmHg (SD = 20.6 mmHg), 18.3 mmHg (SD = 9.0 mmHg) and 23.9 mmHg (SD = 12.3 mmHg) respectively. No significant between patient variability was observed for any of the measurements using general linear models of the difference between measurements and average measurement controlling for time of the measurement during surgery.There is a significant need for continuous, accurate, and precise non-invasive blood pressure (cNIBP) monitoring in acute care patients. Lack of precision and accuracy has been the primary impediments to a wider acceptance of several cNIBP measurement methods. The new CT device investigated here uses pulse contour analysis of the arterial pressure pulse acquired with a hydrostatically coupled sensor system as a means to track blood pressure beat-by-beat. We show here that the CT device is a precise and accurate instrument and can be an attractive alternative for non-invasive measurements.http://my.aami.org/aamiresources/previewfiles/8106002_1306_preview.pdf). A post-hoc power analysis was calculated using a repeated measures analysis to validates that 24 patients corresponds to power greater than 80% to detect differences of 10% at the 0.05 level.This study was conducted to determine what, if any, difference may be between the CT and a-line values. Therefore, because the estimation of the difference between the methods was the outcome of interest, no power analyses for sample size estimates were calculated prior to the study. The final cohort size of 24 was determined primarily by patient availability and is 1.6 times larger than the required size of 15 patients using the AAMI standard when an a-line is used for comparison (The new CT and traditional a-line devices had comparable MAP, systole and diastole values for the measured procedure during the matched 30-min interval. Specific predefined performance requirements regarding accuracy and precision of non-invasive continuous devices are not yet explicitly defined. In this study, we use the AAMI standards; however, this standard was not developed for this specific purpose. While the standard is not intended for continuous blood pressure monitors and excludes dynamic blood pressure episodes as a basis for validation, it is the only applicable standard and for this dataset. Currently all FDA-approved blood pressure monitors utilize this standard as a basis for their approval –16. We hThe comparison method applied here applies more stringent criteria than the AAMI 81060 standard prescribes. The standard calls for a reference reading to be obtained by collecting data from the a-line for at least 30 s before the reading from the device under test, and for at least 30 s after the reading from the device under test. If this range of the reference exceeds 20 mmHg for systole or 12 mmHg for diastole, the reference range is excluded from consideration . OtherwiWith two devices used over the time period, there is a risk for baseline drift and deviations in the measurements. To evaluate the change in performance over time, we plotted the standard deviations of the difference between CareTaker and the a-line values over time Fig. . HoweverWith regard to the differences evident between the a-line and CT, a contributing factor may have been resonance artifacts, that compromised the fidelity of the intra-arterial waveforms. These artifacts, specifically under-damping, may lead to clinically relevant differences between actual and displayed pressure values. The impact of underdamping typically has the greatest effect on systolic pressure and the least on diastolic –21. FurtSome potential limitations of this study include the lack of severely hypotensive patients and the inability to perform sub-group analysis based on various clinical patient parameters and demographics. Future studies should examine the effects of age and various clinical conditions such as heart failure, peripheral vascular disease, arteriosclerosis, diabetes, significant blood loss and hyper/hypotension on the non-invasive measurements obtained with the CT device. The effect of low perfusion in the digits due to cold or other reasons should be also be investigated. Limitations of the current device include the inability to use it in the young pediatric population due to size of the finger cuff and the need for calibration of the blood pressure. Recalibration is also required with significant changes hemodynamics and arterial wall stiffness.The CT device has the potential to replace a-line measurements for accuracy and precision, but as it is a new modality, it has novel issues and will require further validation before larger scale use. One of the CT device’s central practical benefits is the comfortable data acquisition using the finger cuff, increasing potential ease of use and patient comfort. The unique feature for the device is the PDA model that is based on a concrete physical model that explains the structure of the peripheral arterial pressure pulse due to central arterial reflection sites , 6. In aWe have presented evidence that the non-invasive tracking of arterial pressure using the Pulse Decomposition Analysis pulse analysis approach is possible within the guidelines of the ANSI/AAMI 81060 standard. Comparison values were obtained over considerable blood pressure ranges as a result of hemodynamic challenges due to abdominal surgery, supporting the feasibility of this non-invasive and non-intrusive approach to hemodynamic monitoring.