Correlations and biases between the iFR and FFR were compared. The diagnostic performance of the iFR in the groups was calculated, using FFR as the gold standard. The correlation between the iFR and FFR was higher in the high-RPP group than in the low-RPP group. The bias between the iFR and FFR in the high-RPP group was smaller than that in the low-RPP group. The best cutoff value of the iFR for predicting an FFR of 0.8 was 0.90 for all lesions, 0.93 for the low-RPP group, and 0.82 for the high-RPP group. The iFR and RPP showed a weak but a statistically significant negative correlation . This was not observed for the relationship between the FFR and RPP. In conclusion, the RPP affects the relationship between the FFR and iFR. With FFR as the gold standard, the iFR may underestimate and overestimate the functionality of ischemia in the low- and high-RPP groups, respectively.The rate pressure product (RPP) is an index of myocardial metabolism that correlates closely with myocardial hemodynamics. The relationship between the RPP and the fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) is not known. In this study, we investigated the effects of the RPP on the FFR and iFR. We retrospectively enrolled 195 patients (259 lesions) who had undergone invasive coronary angiography and both the iFR and FFR examinations between 2012 and 2017. The RPP was defined as systolic blood pressure multiplied by the heart rate, measured prior to the iFR evaluation. The study population was divided into the low-RPP ( Several studies have shown that reducing myocardial ischemia with coronary artery intervention improves both quality of life and clinical outcomes , 2. The The FFR and iFR correlate well and are similar coronary functional indexes, although they differ in some respects; specifically, FFR is calculated by the pressure ratio during the entire cardiac cycle period under hyperemia, while the iFR is calculated by the pressure ratio during the diastolic cardiac cycle under resting conditions. The rate pressure product (RPP) is calculated as systolic blood pressure multiplied by the heart rate, which is an index of myocardial metabolism that is closely correlated with myocardial hemodynamics . PreviouIn this study, we enrolled patients who had undergone clinically indicated invasive coronary angiography as well as both the iFR and FFR examinations between 2012 and 2017. Because we examined how the RPP affect the relationship between the FFR and iFR, we limited our analysis to patients who had undergone blood pressure and heart rate measurements just prior to the iFR and FFR evaluations. It is difficult to accurately assess the RPP in patients with atrial fibrillation. We, therefore, excluded patients who had had atrial fibrillation. Hemodialysis patients characteristically exhibit specific hemodynamic conditions; therefore, such patients were excluded. We also excluded patients with lesions in the left main trunk and those with bypass grafts. Finally, we excluded patients with ST segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, or New York Heart Association class IV heart failure. We included the patients with unstable angina pectoris, but the stenoses interrogated were the nonculprit lesions.The RPP was defined as the systolic blood pressure multiplied by the heart rate. Blood pressure and heart rate measurements taken just prior to the iFR measurement were used for the calculation. Blood pressure data were extracted from hemodynamic records taken during cardiac catheterization and had been measured using either invasive monitoring of the arterial catheter or a sphygmomanometer. Heart rate was recorded from the electrocardiography monitor or the oxygen saturation monitor. We divided lesions into two groups based on whether the RPP just prior to the iFR measurement for each lesion was greater or lesser than the median RPP; thus, patients in the low- and high-RPP groups had lesions with the RPP <8512 and ≥8512, respectively. Lesion characteristics were compared between the groups as were the correlations and biases between the FFR and iFR.E/eʹ ratio were added to the analysis.Coronary angiography was performed according to standard clinical methods via the radial or femoral arterial approach. Quantitative coronary angiography (QCA) was performed by an independent physician using a computer-assisted automated edge detection algorithm ; the phyµg/kg/min. At the end of each measurement, the pressure sensor was retracted to the tip of the guide catheter to avoid pressure drift.Both the iFR and FFR examinations were performed using either diagnostic or interventional guiding catheters. After administering an intracoronary bolus of nitroglycerin, a coronary pressure wire  was calibrated outside of the body and advanced such that the sensor was positioned at the tip of the guiding catheter where the two pressures were equalized and recorded. After completion of the pressure equalization at the tip of the guide catheter, the guidewire was advanced to a point distal to the stenosis. First, the iFR was directly and automatically measured online using the Volcano Core system (Philips Volcano). Second, the FFR was measured during maximal hyperemia. Hyperemia in the target coronary artery was achieved either with an intracoronary bolus injection of 8–12 mg papaverine or with continuous intravenous administration of adenosine at 150 t-test for normally distributed continuous variables, the Mann–Whitney U test for nonnormally distributed continuous variables, and Pearson's chi-squared test for categorical variables. Correlations between parameters were tested using Pearson's correlation coefficients. Fisher's r-to-z transformation was used to assess the significance of the difference between two correlation coefficients. Bland–Altman analysis was conducted to evaluate the bias and limits of agreement between each parameter. ROC curves were used to evaluate the diagnostic performance of the iFR when identifying a positive FFR measurement using the area under the curve (AUC). Multivariable regression analysis was performed to determine predictors of the FFR and iFR. Variables were included in the multivariable model if they reached p < 0.20 after univariable regression analysis. p values <0.05 were considered to indicate statistical significance. Statistical analyses were performed using JMP statistical software .Continuous data were expressed as means ± standard deviations. Categorical data were expressed as absolute values and percentages. The comparisons were made using Welch's The study protocol was based on the regulations of the hospital's ethics committee. All participating patients provided written informed consent. The study was conducted according to the principles of the 1975 Declaration of Helsinki.2.We enrolled 195 consecutive patients with 259 lesions in this study. The study patient characteristics are shown in The median RPP was 8512  . No significant difference was observed in the QCA parameters.In comparison with the lesions in the low-RPP group, the lesions in the high-RPP group tended to be in older patients, females, nonsmokers, and patients with a history of myocardial infarction. The E/e' ratio in the high-RPP group was higher than that in the low-RPP group : 0.042–0.074) and that of the low-RPP group was 0.097 (95% CI: 0.079–0.115) .p < 0.0001), with 0.93 for the low-RPP group , and 0.82 for the high-RPP group    (Supplem 0.0001) .Using the current iFR cutoff values of ≤0.89, 26.4% of lesions in the low-RPP group would be underestimated, while 16.9% of lesions in the high-RPP group would be overestimated   .p=0.11) and the presence of diabetes mellitus (p=0.04) were potential predictors of FFR. The age (p=0.02), presence of diabetes mellitus (p < 0.0001), prior revascularization (p=0.05), left ventricular mass index (p=0.19), E/e' (p=0.01), glomerular filtration rate (p=0.01), and RPP (p=0.04) were potential predictors of the iFR. Presence of diabetes mellitus was the independent predictor of FFR in multivariable analysis . The presence of diabetes mellitus  and the RPP  were independent predictors of the iFR.The best cutoff value of the RPP to predict discordance of the iFR ≤ 0.89 and FFR > 0.8 was 10950 and 6572 for discordance of the iFR > 0.89 and FFR ≤ 0.8 .The RPP is an index that reflects myocardial metabolism and greatly affects the hemodynamics of the heart , suggestThe primary findings in the present study were as follows: (1) the correlation between the FFR and iFR in the high-RPP group was higher than that of the low-RPP group; (2) the best cutoff value of the iFR for predicting an FFR of 0.8 was 0.90 for all lesions, 0.93 for the low-RPP group, and 0.82 for the high-RPP group; and (3) the iFR and RPP showed a weak but a statistically significant negative correlation. No similar result was found for the FFR and RPP. Moreover, multivariable analysis revealed that the RPP was independently associated with the iFR.The reason for the higher correlation between the iFR and FFR in the high-RPP group might be that the oxygen consumption of the myocardium was increased, resulting in increased coronary blood flow to maintain the oxygen supply in the high-RPP group. If one simply considers the amount of blood flow in the coronary arteries, coronary blood flow under resting conditions in the high-RPP group may increase and be closer to that of the hyperemic condition. Hence, the correlation between the iFR and FFR in the high-RPP group is likely to be increased. The question remains as to whether FFR would be affected in a high-RPP environment. A previous study reported that coronary blood flow under hyperemia did not correlate with the RPP, while coronary blood flow under resting conditions had a significant positive correlation with the RPP . SimilarE/e′ ratio are associated with microvascular dysfunction [As regards the patient characteristics in our study, a total of 58% patients had diabetes mellitus, which is an important covariate for microvascular dysfunction. There are also numerous reports which have suggested that the higher left ventricular mass index and higher function , 15. WheIn this study, the best cutoff value of the iFR for predicting an FFR of 0.8 was 0.90 for all lesions. This value agrees with previously reported values. The best cutoff value for the low-RPP group was 0.93, higher than the standard predictive value of the iFR. The best cutoff value for the high-RPP group was 0.82, lower than the standard predictive value of the iFR. When using the corrected iFR cutoff values of ≤0.93 for the low-RPP group and ≤0.82 for the high-RPP group, a total of 23 (17.8%) lesions should be reclassified as “ischemic” in the low-RPP group and a total of 16 (12.3 %) lesions should be reclassified as “nonischemic” in the high-RPP group.The FFR has hemodynamic independence through dilating and maximizing the coronary microcirculation in hyperemia. The iFR value is sensitive to the RPP fluctuations, while the FFR is less susceptible to the RPP fluctuations. Jain et al. reported that mental stress increased the RPP . In thisThere are several limitations to this study. First, this was a retrospective observational cohort study conducted at a single center, and the number of study patients was relatively small. Second, there were no data on the changes in the iFR values at rest and during exercise in the same patients, and there were also no data on the clinical endpoints. Third, the prevalence of diabetes mellitus and hypertension was higher than those of previous studies. These comorbidities induce structural changes in the myocardium and reduce coronary capacity, possibly influencing the relationship between the iFR and FFR. Fourth, analyses vary depending on which indicator is considered the gold standard. There is, however, abundant evidence in favor of using the FFR, and it is currently the most reliable index recommended in the guidelines. Furthermore, the FFR has customarily been the benchmark for evaluating other nonhyperemic indices. Fifth, there are no data on medication , which might influence the results.Rate pressure products may affect the relationship between the FFR and iFR. Setting FFR as the reference gold standard, the iFR may underestimate the functionality of ischemia in the low-RPP group and overestimate it in the high-RPP group.


The beach chair position that is commonly used in shoulder surgery is associated with relative hypovolemia, which leads to a reduction in arterial blood pressure. The effects of patient positioning on the accuracy of non-invasive continuous blood pressure monitoring with the ClearSight™ system  have not been studied extensively. Our research aim was to assess agreement levels between CS-BP measurements with traditional blood pressure monitoring techniques.n = 10) who required arterial blood pressure monitoring.For this prospective self-controlled study, we included 20 consecutively treated adult patients undergoing elective shoulder surgery in the beach chair position. We performed Bland-Altman analyses to determine agreement levels between blood pressure values from CS-BP and standard non-invasive (NIBP) methods. Perioperative measurements were done in both the supine (as reference) and beach chair surgical positions. Additionally, we compared invasive blood pressure (IBP) measurements with both the non-invasive methods (CS-BP and NIBP) in a sub-group of patients  from the entire cohort; per patient measurements were based on surgical length . The mean difference  in the mean arterial pressure (MAP) between CS-BP and NIBP was − 0.9  in the beach chair position and − 4.9 mmHg  when supine. In the sub-group, the difference between CS-BP and IBP in the beach chair position was − 1.6 mmHg  and − 2.8 mmHg  in the supine position. Between NIBP and IBP, we detected a difference of 3.0 mmHg  in the beach chair position, and 4.6 mmHg  in the supine position.We found clinically acceptable mean differences in MAP measurements between the ClearSight™ and non-invasive oscillometric blood pressure systems when patients were in either the supine or beach chair position. For all comparisons of the monitoring systems and surgical positions, the standard deviations and limits of agreement were wide.DRKS00013773). Registered 26/01/2018.This study was prospectively registered at the German Clinical Trial Register (www.DRKS.de;  Systolic and mean arterial blood pressure tend to be lower in the sitting than the supine position because of relative hypovolemia and reduced cardiac pre-load , 2. In oIt is well known that blood pressure varies with body positon, being lower in the sitting compared to the supine position , 8, 9. TThe primary aim of this prospective self-controlled study carried out under clinical conditions was to assess the level of agreement between two non-invasive BP methods (continuous ClearSight™ (CS-BP) and intermittent NIBP) when shoulder surgery patients were in the beach chair position, and also while they were in the supine position. As secondary aim, we compared non-invasive continuous monitoring with CS-BP to invasive continuous arterial blood pressure monitoring in a subgroup of patients who required additional arterial monitoring. These comparisons were made while the patients were in the beach chair and supine positions. This study was not, however, a formal validation of the device in the beach chair position. Likewise, our study was not evaluating the safety of the absolute BP values measured in different positions. Our institution’s standard of care dictates that we maintain a moderate level of hypotension in patients undergoing this type of surgery; therefore, such controlled circumstances would be unsuitable for a safety study. We hypothesized that the volume clamp or vascular unloading technology provided acceptably low bias compared to conventional blood pressure monitoring, irrespective of patient positioning.www.DRKS.de; DRKS00013773).This prospective, self-controlled study was performed between January and May 2018 at a cantonal level hospital in eastern Switzerland. After receiving approval of our research protocol by the Ethics Committee of Eastern Switzerland , written informed consent of eligible patients was obtained. The study was recorded with the German Clinical Trial Register  adults aged 18 years or older, 2) surgery to be performed under general anesthesia, 3) non acute-trauma (elective) procedures, and 4) patients with a body mass index of > 20 and < 35 kg/mAll general anesthetics were performed according to institutional standards, and all therapeutic decisions were based exclusively on the results of the standard monitoring. After standard monitoring was applied and before anesthesia induction, patients received an interscalene block on the operated arm, when clinically indicated. General anesthesia was induced by propofol target-controlled infusion  and i.v. fentanyl (approx. 1.5 to 3 μg/kg). Tracheal intubation was facilitated by administration of atracurium (0.5 mg/kg). Anesthesia was maintained with propofol, supplemented by fentanyl and/or continuous remifentanil infusion  values between 40 and 60). Patients were moved intraoperatively to the beach chair position. The responsible anesthetist handled fluid administration by Ringers acetate and blood pressure management by administering fluid, varying anesthetic depth or re-dosing opioids, and if necessary, the use of ephedrine. In general, the systolic blood pressure target was 100 mmHg (or maximum 30% lower than baseline) during surgery.The ClearSight™ system consists of an inflatable finger cuff that continuously assesses blood pressure and cardiac index (CS-CI). The CS-BP assessment technique is known as ‘vascular unloading technology’ or ‘the volume clamp method’ and has been described in detail elsewhere , 11. EssThe appropriate ClearSight™ cuff size was determined based on the size of the patient’s index finger. As suggested by the manufacturer, the cuff was placed on the forefinger , and then the values were displayed on the ClearSight™ stand-alone monitor. The ClearSight™ system was zeroed to the ambiance at the level of the proximal end of the upper arm NIBP cuff. CS-BP was electronically recorded in 20-s intervals.Non-invasive intermittent oscillometric blood pressure measurements  were obtained from the patient’s upper arm and recorded during the anesthetic in 2.5 to 5-min intervals depending on the patient’s hemodynamic situation. The size of the blood pressure cuff was selected based on the manufacturer’s recommendation.Invasive continuous arterial blood pressure monitoring was performed after cannulation of the radial artery  and displayed on the vital signs monitor . The arterial monitoring system was zeroed to the ambiance at the level of the proximal end of the upper arm NIBP cuff.The main study outcomes were mean values of ABP, heart rate, and cardiac index (CI). Different blood pressure monitors were used simultaneously on the same arm in every study participant, which was the non-operated arm. Recordings from the ClearSight™ system were done by an investigator who was not responsible for the anesthetic. We synchronized the clocks of the ClearSight™ system and the vital signs monitor before beginning with each patient’s measurements. Blood pressure was reported as systolic, mean (MAP), and diastolic. These were recorded in a supine resting position before and after anesthesia induction, after bringing the patient in the beach chair position and every 30 min thereafter, at the end of anesthesia in the supine position and then one last time after emergence from anesthesia while still in a supine position see Fig. . During Mean values of ABP, heart rate, and cardiac index (CI) were obtained during supine positioning and were compared to mean values obtained in the beach chair position Fig.  with exaThe MAP values with ≥10% deviation from the standard method were assessed for both CS-BP (to NIBP and IBP) and IBP (to NIBP) measurements. It was calculated how often an increase or decrease of ≥10% between subsequent MAP measurements of the standard method was accompanied by a change in CS-BP MAP in the same direction  or decrease (< 0) between subsequent measurements).p-values can be considered nominal and unadjusted for multiple testing. A power calculation was not performed since this was primarily a descriptive study. However, we estimated 20 patients with an average of 5 measurements (per patient and position) resulting in 100 data points would be sufficient when making comparisons using Bland-Altman plots [Reported an plots . All stap < 0.001). Heart rate (p = 0.083) and CI (p = 0.388) did not differ. No complications from any of the methods were observed.Twenty patients were included, and a total of 230 time points  time points per patient) were assessed. All patients underwent standard non-invasive blood pressure monitoring, and a subgroup of 10 patients also underwent invasive blood pressure monitoring . General patient and anesthesia data are shown in Table The MAP Bland-Altman analyses showed a mean of the differences  between CS-BP and NIBP of − 2.9 mmHg , between CS-BP and IBP of − 2.6 mmHg , and between NIBP and IBP of 0.9 mmHg   between CS-BP and NIBP of − 4.9 mmHg , between CS-BP and IBP of − 2.8 mmHg , and between NIBP and IBP of 4.6 mmHg  , but not to heart rate . When compared to IBP, there was also a significant negative correlation to cardiac index , but not to heart rate .Spearman’s rank correlation of differences in MAP values for CS-BP compared to NIBP (in both supine and beach chair positions) showed a weak but significant negative correlation to CS-CI  MAP comparisons indicated a ≥ 10% deviation between CS-BP and NIBP measurements. The corresponding number for CS-BP MAP compared to IBP was 46.5% (46/99). 35.7% (35/98) MAP comparisons differed ≥10% between NIBP and IBP measurements.For consecutive MAP values of NIBP and IBP, an increase or decrease of ≥10% was accompanied by a change in CS-BP MAP in the same direction in 94% (79/84) compared to NIBP, and 95.3% (41/43) compared to IBP. When there was an increase or decrease of ≥10% in IBP, it was accompanied by a change in NIBP in the same direction in 90.7% (39/43).In this study, a continuous non-invasive blood pressure monitoring system (ClearSight™) was compared with oscillometric and invasive blood pressure monitoring in patients undergoing shoulder surgery in the beach chair position. Our main finding was that the accuracy of the ClearSight™ blood pressure readings was not worse in the beach chair position than in the supine position.ClearSight™ and other similar systems were validated using invasive reference methods in different clinical settings, which led to varying and contradictory results , 18, 20.During elective orthopedic surgery with patients in the supine position, Balzer et al. found a tendency to higher precision compared to IBP for the volume clamp method than for NIBP ; howeverThe Association for the Advancement of Medical Instrumentation  defines 5 mmHg (± 8 mmHg) as a clinically acceptable agreement level when comparing a test to a reference method . HoweverIn more than 90% of the time during our investigation, the ClearSight™ system detected changes in the arterial blood pressure of 10 % or higher. Furthermore, the system’s performance was not worse than intermittent standard blood pressure monitoring when compared to invasive arterial blood pressure assessment. However, there is a greater potential for bias when interpreting intermittent versus continuous monitoring. The interpretation of trends rather than absolute values may be more useful with this new system.Interestingly, there was a negative correlation between the MAP differences and the cardiac index . One possible explanation was that signal quality was less optimal with lower cardiac indices. However, this remains speculative.Our study had limitations. First, we included a relatively small number of patients, and we used invasive blood pressure measurements as a reference method for only half of the cohort. We chose to limit the use of invasive technique to only those who needed additional arterial blood pressure monitoring because we did not want to expose the other patients to unnecessary risk of complications, such as infection. As a result of the small sample size, we observed wide standard deviations. Second, we were obligated to keep the blood pressure values in a narrow range due to clinical standards for orthopedic surgeries, which prevented us from performing an error grid analysis as proposed by Saugel et al.  Third, gThe levels of agreement among the three blood pressure measurements methods  were comparable between the beach chair and supine positions. Non-invasive continuous blood pressure monitoring with the volume clamp method has the potential to bridge the gap between non-invasive intermittent oscillometric monitoring and continuous invasive blood pressure monitoring.


Vitamin D is one of the known lipoprotein hormones with metabolic properties. We aimed to determine the serum 25-hydroxy vitamin D concentration in overweight/obese subjects with diabetes mellitus type Ⅱ (DM Ⅱ) in association with systolic and diastolic blood pressure and quality of life compared with healthy participants.The current case-control study was carried out among 80 overweight/obese subjects with DM Ⅱ, and 77 healthy subjects matched by sex, age and body mass index (BMI). Serum 25-hydroxyvitamin D concentration was measured by ELISA method. In order to examine the quality of life, the Persian version of SF36 questionnaire was used.There was significant difference between diabetic and healthy subjects considering serum 25-hydroxyvitamin D concentration (p=0.012). Serum 25-hydroxyvitamin D concentration was inversely correlated with diastolic blood pressure (p=0.02) and positively associated with physical function (p<0.001), social function (p<0.001) and general health (p<0.001) components of quality of life in diabetic subjects and physical health sub-scale (p=0.004) in all participants.Serum 25-hydroxyvitamin D concentration was significantly lower in diabetic subjects in comparison with healthy controls. There was a significant reverse relationship between serum concentrations of 25-hydroxyvitamin D with diastolic blood pressure and on the other hand, a significant positive relationship with physical function, social function and general health components and physical health subscale of quality of life in participants with DM Ⅱ. DM ion (HTN) . Iran ison (HTN) . More thon (HTN) , 9. Overweight and obesity are important risk factors for vitamin D deficiency, and a recent observational study in the general population has shown a negative correlation between the vitamin D deficiency and blood pressure measured in outpatient department . On the Considering the importance of vitamin D in regulating blood pressure, as well as insulin resistance, and the contradiction between the results of the published studies, the aim of this investigation was to measure the serum concentration of 25-hydroxyvitamin D in overweight/obese subjects with DM Ⅱ in association with systolic and diastolic blood pressure and quality of life compared with healthy subjects. This is a case-control study. The target population of the study was all patients with DM Ⅱ in Tabriz city. Cluster-random sampling was carried out in the health centers of Tabriz. Tabriz has 82 health centers in 10 different municipal districts, with the characteristics of all diabetic patients including phone number and address at the centers. First, 5 municipal districts were randomly selected  and 9. TInclusion criteria were age 20 and above, diagnosis of DM Ⅱ and body mass index (BMI) of 25 kg/m2 and above. Exclusion criteria were type 1 diabetes, previous hypertension or antihypertensive drug use, taking any dietary supplement including vitamin D supplementation, following special diets , history of known liver or kidney disease, the presence of malignancy or the history of recent acute illnesses, pregnant and lactating women, history of taking medications affecting vitamin D levels, taking corticosteroids, anticonvulsants, estrogen, androgen and oral contraceptive (OCP), history of pancreatitis, hypo- or hyperthyroidism, Cushing’s disease, Addison’s disease and renal failure. The control group was randomly selected from referrals to health centers without known history of illness matched by age, sex and BMI with a 1:1 ratio. Exclusion criteria for control group were blood glucose level ≥ 120 mg/dl and HbA1c of 6.5% and higher .Sample size: Considering the level of blood pressure in the case and control groups as the primary outcome, and considering the observations in the Nayak study , 24.2 anIf the conditions were met, written informed consents were obtained and the demographic and physical activity questionnaires and anthropometric checklist were completed. Dietary intake: In order to investigate the food intake, a 3-day food record was obtained and macro- and micro-nutrients intakes were determined through U.S. Department of Agriculture (USDA) food composition  with chaAnthropometric measurement: Participants’ weight was evaluated by a standard scale  following an overnight fasting. Participants’ height was evaluated by a standard scale (Seca 206 roll-up measuring tape). BMI was computed through dividing the weight (kg) by the square of height (m2). BMI between 18.5 and 24.9 has been defined as normal. BMI values greater than 25 and 30 are regarded as overweight and obese, respectively . PhysicaVitamin D measurement: Fasting blood samples were collected. Serum 25-hydoxyvitamin D concentrations were measured in the laboratory of Emam Reza Hospital in Tabriz as a reference laboratory, following all the essential strategies for blood sampling and prohibition of blood hemolysis during collection. Blood samples were rapidly centrifuged at 3500 rpm for 10 to 15 minutes to isolate the serum. Samples were stored at -80 ° C till the laboratory tests were carried out. To minimize the error, the measurement of each biochemical parameter was done by one individual, one kit and one specific device. Serum 25-hydroxyvitamin D concentrations were admeasured by ELISA. All stages were implemented based on the directions of the kits . Experimental reliability was investigated by sending 5 duplicates with two different names. Individuals were divided into three groups of deficient (0-19.9 ng/ml), insufficient (20-29.9 ng/ml) and sufficient (≥ 30 ng/ml) groups based on 25-hydroxyvitamin D concentration .Blood pressure measurement: The blood pressure of participants was measured in the sitting position from the right arm of the subjects by a Riester manometer, Diplomat model with accuracy of ±3 mm Hg after 15 minutes of rest per visit. Measurements were executed twice, with interval of 15 minutes. Quality control of the device was performed every month. It was recommended that people should not perform intense exercises, eating, smoking, drinking except water and using drugs that affect blood pressure, for at least 1 hour before measuring blood pressure. The cuff was 12-12.5 cm in width and the height was at least two-thirds of the arm’s circumference. For analysis, the mean of two measurements was used.Quality of life: The tool used to measure quality of life was the Persian version of the 36-item questionnaire SF36. This questionnaire is valid for assessing the quality of life under various conditions, including diabetes. The validity and reliability have been evaluated and accepted in Iran, and the Cronbach’s alpha has been between 0.77-0.9 for eight domains . StatistThe normal distribution of data was assessed using the Kolmogorov-Smirnov test and also descriptive evidence such as skewness and kurtosis plus appropriate and reasonable standard deviations (compared to the mean). Chi-square test was applied to compare qualitative variables between the two groups. Independent samples t-test was applied to compare quantitative variables between the two groups. Logistic regression analyses were performed to define whether 25-hydroxyvitamin D concentration was a significant factor correlated with occurrence of HTN. Lastly, partial correlation analyses were applied for analyzing correlations. Age, sex and BMI were considered as control variables. Values of p<0.05 were considered as statistically significant. Ethical considerations: The aims and the method of the investigation were described for each individual at the start of the study, and written informed consent was achieved from each study participant. The participants were able to withdraw the study at any stage during the study, without giving any reason. No extra charges, complication or intervention were enforced on participants, and they were not excluded from their routine therapies. This study has been approved by the Ethics Committee of the Research Deputy of Tabriz University of Medical Sciences (IR.TBZMED.REC.1396.823).2) and 45 (56.25%) cases were obese (BMI≥30 kg/m2), compared to 33 (42.58%) and 44 (57.14%) in the control group (p=0.910). The majority of participants had no or limited education (i.e. 57 (71.2%) subjects in case group and 53 (68.8%) subjects in control group). Physical activity did not differ among cases and controls (p=0302). In this study, 80 overweight and obese patients with DM Ⅱ, and 77 healthy subjects matched by age, sex and BMI as control group, were examined. The results of logistic regression analysis of predictor factors of high systolic blood pressure, suggested that people who have vitamin D deficiency will be affected by high systolic blood pressure approximately 1.11 times more likely than those with normal vitamin D, which is not statistically significant . The results also showed that along with one unit increase in the BMI, the chances of having high systolic blood pressure in subjects will increase by 11% .The results of logistic regression to predict high diastolic blood pressure, showed that subjects with vitamin D deficiency develop high diastolic blood pressure approximately 2.3 times more likely than those with normal vitamin D . The results were approximately 2.2 times higher with consideration of weight  and approximately 2.2 times higher with consideration of BMI  as the confounding factors.According to the findings, 51.3% of diabetic patients had vitamin D deficiency, 27.5% had insufficiency and 21.2% were sufficient, while in healthy controls, these levels were 36.4%, 23.4% and 40.2%, respectively, and there was a considerable difference between the two groups in this regard. Vitamin D deficient subjects were 2.5 times more probable to develop DM Ⅱ in comparison with those with sufficient vitamin D status. Serum vitamin D concentrations and all aspects and sub-scales of quality of life were significantly lower and diastolic blood pressures were significantly higher in diabetic patients compared with healthy controls.Several investigations have revealed the elevated prevalence of vitamin D deficiency in tropical and subtropical countries, including Iran, Turkey, China, India and Saudi Arabia -40. The According to the findings of our study, there was a noteworthy inverse association between serum concentrations of 25-hydroxyvitamin D with diastolic blood pressure in the patients with DM Ⅱ in contrast to healthy controls. Subjects with vitamin D deficiency developed high diastolic blood pressure approximately 2.3 times more likely than vitamin D sufficient ones.et.al  were associated with elevated levels of diastolic blood pressure  in adolescents compared with normal concentrations. Systolic blood pressure tend to increase in the vitamin D deficient subjects . The association between systolic blood pressure and serum vitamin D concentrations was a U-shaped relationship and its relationship with diastolic blood pressure was reverse . At the The association between serum concentrations of 25-hydroxyvitamin D and quality of life in diabetic patients seen in the our study is along with the conclusions of several previous studies in other disorders. For example, in a cross-sectional study, there was a direct correlation between vitamin D deficiency and quality of life in elderly women with osteoporosis and multiple disabilities . In the Results showed that with each increasing unit in the BMI, the chances of having high systolic blood pressure will increase by 11%. Several studies have been carried out on the effects of vitamin D deficiency on obesity -61. It hFrom the study limitations, we can refer to the relatively small sample size in the case (n=88) and control (n=77) groups, the impossibility of determining the causal relationship between serum concentration of 25-hydroxyvitamin D and high systolic and diastolic blood pressure due to the observational nature of the study, the lack of measurement of inflammatory markers such as CRP or ESR, and their associations with the serum 25-hydroxyvitamin D concentrations and failure to evaluate the effect of abnormal blood pressure on future blood pressure due to the need for long-term follow-up. On the other hand, despite examining several confounding variables, other undetected confounders may possibly modify the results of the present study. Despite these limitations, the present study is one of the few studies to investigate the relationship between the serum concentration of 25-hydroxyvitamin D and risk of high blood pressure in obese/overweight diabetic patients. serum concentration of 25-hydroxyvitamin D is significantly lower in patients with DM Ⅱ than healthy subjects. There is a significant reverse relationship between serum concentration of 25-hydroxyvitamin D and diastolic blood pressure and a significant positive relationship with the components of physical and social function and general health, and the subscale of physical health of quality of life in patients with DM Ⅱ. Diabetic patients with vitamin D deficiency were 2.2 times more probable to have high diastolic blood pressure compared with those with normal vitamin D status.In conclusion


Inadequate coronary adenosine response is a potential cause for false negative ischemia testing. Recently, the splenic switch-off (SSO) sign has been identified as a promising tool to ascertain the efficacy of adenosine during vasodilator stress cardiovascular magnetic resonance imaging (CMR). We assessed the value of SSO to predict adenosine response, defined as an increase in myocardial blood flow (MBF) during quantitative stress myocardial perfusion 13 N-ammonia positron emission tomography (PET).stress) and rest.We prospectively enrolled 64 patients who underwent simultaneous CMR and PET myocardial perfusion imaging on a hybrid PET/CMR scanner with co-injection of gadolinium based contrast agent (GBCA) and 13N-ammonia during rest and adenosine-induced stress. A myocardial flow reserve (MFR) of  > 1.5 or ischemia as assessed by PET were defined as markers for adequate coronary adenosine response. The presence or absence of SSO was visually assessed. The stress-to-rest intensity ratio (SIR) was calculated as the ratio of stress over rest peak signal intensity for splenic tissue. Additionally, the spleen-to-myocardium ratio, defined as the relative change of spleen to myocardial signal, was calculated for stress . Mean hyperemic and rest MBF were 2.12 ± 0.68 ml/min/g and 0.78 ± 0.26 ml/min/g, respectively. MFR was significantly higher in patients with vs. patients without presence of SSO , but there was only a weak inverse correlation between SMRstress and MFR  as well as between SIR and MFR .Sixty-one (95%) patients were coronary adenosine responders, but SSO was absent in 18 (28%) patients. SIR and SMRThe presence of SSO implies adequate coronary adenosine-induced MBF response. Its absence, however, is not a reliable indicator for failed adenosine-induced coronary vasodilatation. Due to its rapid onset of action, its short half-life and the good tolerability and safety profile, adenosine is a widely used vasodilator for ischemia testing in myocardial perfusion imaging (MPI) using single photon emission computed tomography (SPECT), positron emission tomography (PET), and cardiovascular magnetic resonance imaging (CMR). However, induction of maximal coronary vasodilation is a crucial prerequisite for obtaining high diagnostic accuracy concerning the detection of obstructive coronary artery disease (CAD) –4. WhethContrary to modalities relying on the detection of relative regional differences in myocardial perfusion, such as CMR and SPECT, PET MPI allows for absolute quantification of myocardial blood flow (MBF) and calculation of myocardial flow reserve (MFR) . AdenosiData of this prospective single-center study were derived from ongoing PET/CMR projects. We assessed patients who underwent cardiac PET/CMR for evaluation of CAD or cardiomyopathy. Written informed consent was obtained from all participants, and the study protocol was approved by the local ethics committee (KEK-ZH-Nr. 2014-0187 and BASEC-Nr. 2018-00170). Patients aged ≥ 18 years without any contraindications against CMR , adenosine , or PET  were included. This study was partially funded by the Swiss National Science Foundation (SNSF Project Nr. 175640).CMR and PET datasets were acquired using a hybrid PET/CMR device incorporating a 3 T CMR and a latest-generation PET scanner with time-of-flight (TOF) . All patients were asked to refrain from caffeine intake for at least 12 h before the examination. The stress protocol consisted of 6 min of adenosine infusion with a weight-adapted dose of adenosine (140 μg/kg/min). A body mass index adapted dose of 13N-ammonia  and a weight-adapted dose of GBCA  (0.1 mmol/kg) was simultaneously injected 3 min into adenosine stress. Dynamic PET data acquisition consisted of 21 frames , followed by an electrocardiogram (ECG)-gated static acquisition over 10 min. Resting perfusion imaging was performed using an identical acquisition protocol after a minimum of 15 min following the stress acquisition according to Society for Cardiovascular Magnetic Resonance (SCMR) guidelines . Fi. Fi14]. Descriptive statistics were used to examine clinical data. Values are presented as averages ± standard deviations or as total numbers and as percentages, where applicable. Patients were stratified into groups according to the presence or absence of SSO and according to a positive or negative HR response . Comparison between the groups was performed using a Chi2-test in nominal or students’ t-test and Mann–Whitney-test in normally distributed and non-parametric variables, respectively. Correlation analysis between SIR and MFR, SMR and MFR, as well as between the HR increase from rest to stress and MFR was performed using Pearson analysis. A cut-off value for SIR and SMR for predicting the presence of SSO was calculated using receiver operating characteristic (ROC) analysis. Statistical analysis was performed using SPSS .A total of 67 patients were included in our study. The spleen was visible within the CMR field-of-view in 64 (96%) patients. The remaining 3 (4%) patients were excluded from further investigations. Baseline characteristics and PET findings are given in Table The mean injected activity of 13N-ammonia during PET was 297 ± 98 MBq and 463 ± 103 MBq for stress and rest imaging, respectively. Mean hyperemic and rest MBF were 2.1 ± 0.7 ml/min/g and 0.8 ± 0.3 ml/min/g, respectively. Mean MFR was 2.9 ± 1.0. Three (5%) patients with an MFR ≤ 1.5 and without any signs of ischemia neither in PET nor CMR were classified as adenosine non-responders. Three (5%) additional patients with severe coronary artery disease had an MFR ≤ 1.5 but presented with clear signs of ischemia in 13 N-ammonia PET and CMR and were therefore classified as adenosine responders.SSO was present in 46 (72%) patients. Inter-rater reliability was excellent . Among the three adenosine non-responders, two patients did not present with SSO, but one patient showed SSO. MFR differed significantly in patients with vs. patients without presence of SSO . Splenic stress-to-rest SIR was significantly lower in patients with vs. patients without presence of SSO .stress was significantly lower in patients with vs. patients without presence of SSO . ROC analysis yielded an optimal cut-off value of SMRstress for predicting presence of SSO of 1.53 .ROC analysis yielded an optimal cut-off value of SIR for predicting presence of SSO of 0.71 . SMRstress . By contrast, there was no correlation between SMRstresst or SIR and the total increase of HR during adenosine .A weak correlation was found between MFR and SIR  as well as between MFR and SMRHR increased significantly from rest to stress , and 29 (45%) patients had a positive HR increase of ≥ 10 bpm. There was a trend towards higher MFR in patients with vs. patients without a positive HR response  but there was no difference in the proportion of patients with and without a positive HR response among patients with or without SSO (p = 0.23).To the best of our knowledge, this is the first study investigating the performance of SSO to predict coronary adenosine response on a hybrid PET/CMR device with co-injection of GBCA and 13N-ammonia using PET-derived MFR as the standard of truth. While we found that 95% of the patients were coronary adenosine responders, SSO was absent in 28% of the patients. Furthermore, there was only a weak correlation between SMR and MFR as well as between SIR and MFR. Hence, from our results, we conclude that the absence of SSO should not necessarily lead to the conclusion that a patient failed to respond to adenosine. By contrast, however, the presence of SSO in case of normal stress perfusion CMR is a strong indicator for a true negative finding.Our findings are in line with the results of Kuijpers et al. who demonstrated that SSO failed to predict adenosine non-responders after caffeine intake . By contIn our study, SSO was present in 72% of the patients, a proportion which is slightly lower than previously described by Manisty et al. (90%) . HoweverThe present study extends our knowledge and understanding of the SSO sign. While our results question its value as a reliable marker of inadequate adenosine response, future prospective studies—ideally placebo- or caffeine-controlled—are also needed. It is noteworthy and important, however, that our results on the other hand also carry the reassuring message that the presence of SSO is a strong marker for adequate coronary adenosine response, therefore increasing a readers’ confidence in case of a normal CMR myocardial perfusion scan.In the present study, we used a binary system to classify patients into responders vs. non-responders. This may be seen as an over-simplification in light of some studies suggesting a more graduated adenosine response, depending on receptor density and responsiveness of adenosine receptors .The presence of SSO implies adequate coronary adenosine-induced MBF response. Its absence, however, is not a reliable indicator for failed adenosine-induced coronary vasodilatation.


A significant, moderate correlation was found between BSA on SBP was found ; and a significant, weak correlation between BSA and DBP was found  is one of the greatest non-communicable diseases affecting both sexes in all human populations; and it is a major cause of death and morbidity across the world. The purpose of this study was to investigate the prevalence of pre-hypertension, hypertension and investigate the association between blood pressure (BP) and body weight (looking into body mass index (BMI) and body surface area (BSA)). Method: A cross-sectional study of adolescents aged 13–19 years was conducted at three secondary schools consisting of 121 females and 97 males. Data on height; weight; and blood pressure was collected from all participants. BMI and BP percentiles were calculated for each participant. Results: The prevalence of pre-hypertension and hypertension in males was 28.9% and 10.3% compared to 25.6% and 7.4% in females. The prevalence of pre-hypertension and hypertension in adolescents who are overweight/obese was 7.3% and 2.7%. A weak positive association between BMI; systolic blood pressure (SBP) and diastolic blood pressure (DBP) was found ( The WHO defines non-communicable diseases (NCDs) as conditions that are influenced by environmental, behavioral, physiological and genetical factors . The burHypertension in adolescents is defined as systolic and/or diastolic blood pressure greater than the 95th percentile for height, sex and age. Normal BP is defined as below the 90th percentile, whereas BP above the normal BP is defined to be between 90th and 95th percentile for height, sex and age but exceeds 120/80 mmHg . The diaHigh blood pressure is the most common disease identified in overweight adolescents, and persistent high blood pressure can lead to mortality in adulthood. High blood pressure has been attributed to approximately 12.8% of the deaths worldwide . SeveralThis is a cross-sectional study, in which data was collected among urban and rural secondary-school participants, based in the Polokwane region of the Limpopo province, which is located the north of South Africa. The province is still under-resourced compared with other provinces in South Africa. It is characterized by high levels of unemployment, reflecting a transition between traditional and western lifestyles since the majority of the young adults work in towns and cities and return home for periodic visits ,7. ThreeAdolescents with cardiovascular conditions.Females who are pregnant or breastfeeding.Adolescents taking acute or chronic medication.Adolescents with orthopedic injuries.Adolescents who are using supplements .Adolescents with any of the following conditions were excluded from the study:Blood pressure was measured with an Omron blood pressure device as described by the American Heart Association . The cut2). Body mass index cut-offs was as follows: below 18.5 kg/m2—underweight, 18.5 kg/m2 to 24.99 kg/m2—normal, 25 kg/m2 to 29.99 kg/m2—overweight and above 30 kg/m2—obese [The field workers were trained to collect anthropometric data. All study participants underwent a series of anthropometric measurements  according to standard procedures of the International Society for the Advancement of Kinanthropometry . The weim2—obese . Body suDue to the lack of previous data assessing the impact of BSA on BP, we categorized BSA using quartiles to report more useful findings on the association of BSA with BP. Participants were classified as obese or non-obese by using BSA median values of BSA ≥ 1.6 (obese) or BSA < 1.6 (non-obese) . Each pap-value of <0.05.IBM SPSS Version 25 was utilized to conduct statistical analysis. Distribution frequencies were calculated for all variables, and any outlier was verified against the raw data and where necessary, the outlier was removed. To describe and characterize the samples, descriptive statistics were calculated for all the variables in order to indicate frequencies (expressed as percentages), means and standard deviations. This served as an indication of prevalence. The estimation of prevalence was presented by sex. The association between BP and anthropometric data (BMI and BSA) was tested using the Pearson correlation. Participants were divided into different age and sex categories for further analysis of the results. The probability value for statistical significance for all tests was set at a Measurements that were taken for both anthropometric (weight and height) and blood pressure were repeated throughout the study. If the first measurement differed from the second measurement by more than 5% for anthropometric measurements or 5 mmHg for blood pressure, a third measurement was taken to ensure the accuracy of the measurements. An average of the two closest measurements taken was utilized.A complete BP and anthropometric data were obtained from 218 participants . The average age and mean systolic blood pressure for males was significantly higher than in females, whereas mean diastolic was significantly higher in females compared to males. Females had a heavier weight than males, whereas males were taller than females. Females also had a significantly higher BMI than in males, whereas the mean average for BSA was the same for both sexes .The prevalence of pre-hypertension and hypertension was 28.9% and 10.3% in males whereas in females it was 25.6% and 7.4%. The overall prevalence of pre-hypertension and hypertension was 27.3% and 17.1%, respectively . The preThe prevalence of pre-hypertension in adolescents who were overweight and obese was 3.2% and 4.1%. The prevalence of hypertension in adolescents who were overweight and obese was 2.3% and 0.4%. The combined prevalence for pre-hypertension of overweight and obesity was 7.3%, whereas the combined prevalence for hypertension of overweight and obesity was 2.7%, respectively .p-value = 0.001).A significant weak positive correlation of BMI on SBP  and BMI r = 0.407, p-value = 0.001); and a significant, weak positive correlation between BSA and DBP .A significant, moderate positive correlation was found between BSA on SBP  was foun and DBP  was founThis was a cross-sectional study that investigated the prevalence of pre-hypertension and hypertension and aimed to explore the possible association between blood pressure and body weight among male and female adolescents in the Polokwane local municipality. The results obtained indicated a significant difference in BP between males and females’ adolescents. A positive association was found between BMI and BP (SBP and DBP); and between BSA and BP (SBP and DBP). The results showed that females had a significantly higher weight/BMI than males subsequently; the prevalence of overweight and obesity was higher in females compared to males. The relationship between overweight/obesity and hypertension has long been investigated, with the risk of hypertension being up to five times higher among obese people than among those of normal weight .A study by Pate et al.  indicateThe prevalence of pre-hypertension and hypertension was higher in males compared to females, this shows a similar finding compared to the study conducted in Mthatha, South Africa . The rear = 0.198, p-value = 0.001); ). A study conducted in the western Africa, Nigeria indicated a significant and a weak positive correlation between BMI and BP (SBP and DBP) ; ) [r = 0.255, p-value < 0.01); and between BMI and DBP  [A positive association of BMI with SBP and DBP for the whole population was found; these results confirm the findings obtained by Erlingsdottir et al.  which in 0.010)) ; and sim < 0.01) . Our resHowever, it is still unclear of what could cause an elevation in blood pressure; some studies suggest that the mechanism that causes an increase in blood pressure may be due to pro-inflammatory immune responses in the cytokines and an increase in adipocyte secretion of adipokines which physiological dysfunction leading to an increase in blood Pressure . A numbe


A lacunar infarction (LACI) can cause damage to the surrounding brain tissue and place an individual at greater risk for future major stroke. LACI is associated with hypertension and hypertension is associated with left atrial enlargement. It is important to identify a high-risk patient who is more vulnerable to suffering a LACI in hypertensive group. So, we studied whether left atrium size is an independent risk predictor for LACI in hypertensive patients. We performed cross-sectional analysis of 365 patients with hypertension at Shanghai Ninth People’s Hospital from January 2016 to January 2017. The results showed that left atrial diameter(LAD), left atrial volume (LAV) and the ratio of left atrial diameter to left ventricular diameter (LAD/LVD) were significantly associated with LACI in hypertensive patients. Based on the ROC curve analysis, the area under the ROC curve (AUC) of LAV used to predict LACI was 0.737 (95% CI: 0.686 – 0.788), and the AUC of LAD/LVD was 0.784 (95% CI: 0.737 – 0.830). The optimal cut-off value for LAV was 30.14, and the sensitivity and specificity were 72% and 63%, respectively. The optimal cut-off value for LAD/LVD was 0.757, and the sensitivity and specificity were 77% and 70%, respectively. LAV or LAD/LVD played an important role in LACI with hypertension and could be an independent risk factor in hypertensive patients. Lacunar infarct (LACI), a small deep infarct that results from occlusion of a penetrating artery, accounts for approximately one-quarter of all ischemic strokes . The corWith the rising awareness of the multiple risk factors for LACI, early detection of those risk factors, especially those related to cardiovascular diseases, for the prevention of target organ damage has become a reality. The risk factors for LACI are advanced age, chronic hypertension, smoking and diabetes mellitus . Among tThe prevalence rate of hypertension in China is relatively high; however, patients’ awareness about hypertension treatment and control is poor. From 1991 to 2011, approximately one-fifth of Chinese adults were hypertensive, but only 17.5% of hypertension was controlled. Peng J et al studied 480 elderly hypertensive Chinese patients and found that left atrial enlargement is independently associated with a longer duration of hypertension in elderly hypertensive patients with preserved LVEF , and LAD/LVD was associated with LACI with an odds ratio (OR) of 8.094   older than 18 years and 2) primary hypertension. The following conditions were exclusion criteria: 1) massive cerebral infarction (isolated ischemic lesions > 20 mm); 2) atrial fibrillation; 3) rheumatic heart valve disease; 4) heart failure and other possible causes of heart thrombosis; and 5) concomitant severe diseases such as liver, kidney, hematopoietic system and endocrine system disorders.All patients completed a questionnaire and underwent a complete routine clinical and cardiac laboratory evaluation including age, sex, family history physical examination, electrocardiogram, and blood pressure monitoring. Patients were routinely referred to magnetic resonance imaging (MRI) with diffusion-weighted images (DWI) by the neurologist in charge of them after admission to the hospital . Because some patients were unable to undergo MRI due to contraindications such as a pacemaker, 61 patients underwent only CT scanning. Isolated ischemic lesions on MRI, DWI or CT were defined as lacunar infarcts if <20 mm and located subcortically or in the brainstem. Neuroimaging was reviewed by a stroke neurologist (HN) with extensive experience (>15 years) in the interpretation of stroke MRI and CT images. The study protocol was approved by the Shanghai Ninth People’s Hospital Ethics Committee and Research Board. Written informed consent was obtained from all study participants.Transthoracic echocardiography (TTE) was carried out by using a commercially available ultrasound device . Images were obtained from parasternal and apical windows using 2D, M-Mode, and Doppler echocardiography. TTE was performed in all patients, and left ventricular ejection fraction (LVEF) was calculated as (1-end-systolic volume/end-diastolic volume) × 100%. Chamber size was measured by the biplane area-length method on two-dimensional echocardiography. The left atrial diameter was measured at the end of ventricular systole using the M-Mode two dimensional or anteroposterior linear dimension standard technique . The ellStatistical analysis was performed using SPSS 17.0 software. Summary statistics were expressed as the mean ± standard deviation for continuous variables, and frequencies and percentages for discrete variables. Fisher’s exact test and the Pearson Chi-square test were used to evaluate categorical variables. A multivariable analysis using multiple logistical regressions was performed for all significant variables in the univariable analysis  and for other potentially confounding variables . Odds ratios (ORs) 95% confidence intervals (CIs) were calculated for the primary and secondary outcomes. P values <0.05 were considered statistically significant.


Lactic acidosis is a common complication of status asthmaticus in adults. However, data is sparse in children. The aim of this study was to describe the prevalence and risk factors for lactic acidosis in children hospitalised for acute moderate or severe asthma. A total of 154 children 2–17 years of age were enrolled in a prospective observational study conducted in a tertiary hospital. All had capillary blood gas assessment 4 h after the first dose of salbutamol in hospital. The primary endpoint was the prevalence of lactic acidosis. Potential contributing factors such as age, sex, BMI, initial degree of asthma severity, type of salbutamol administration , steroids, ipratropium bromide, and glucose-containing maintenance fluid represented secondary endpoints. All in all, 87% of patients had hyperlactatemia (lactate concentration > 2.2 mmol/l). Lactic acidosis (lactate concentration > 5 mmol/l and anion gap ≥ 16 mmol/l) was observed in 26%. In multivariate analysis, age more than 6 years , glycemia above 11 mmol/l (OR = 3.2 95% CI 1.4–7.4), and salbutamol administered by nebuliser  were identified as risk factors for lactic acidosis in children with moderate or severe asthma.Conclusion: Lactic acidosis is a frequent and early complication of acute moderate or severe asthma in children. Asthma is characterised by chronic airway inflammation and hyperresponsiveness. During an acute exacerbation, inhomogeneous airway narrowing and obstruction lead to hypoxemia. Compensatory hyperventilation mediated by pulmonary mechanoreceptors conducts to respiratory alkalosis, the most frequent acid-base disturbance observed in acute asthma. If not treated properly, progressive respiratory insufficiency may occur with hypercapnia and respiratory acidosis .Lactic acidosis is another blood gas alteration observed during moderate or severe asthma. Multiple mechanisms have been proposed. Some have evoked reduced tissue perfusion or overuse of respiratory muscles under hypoxic conditions . Others Lactic acidosis is now a well-known complication of status asthmaticus in adults. Case reports and some retrospective and rare prospective studies describe a transient lactic acidosis as a side effect of high doses b2-agonists used in acute asthma treatment. However, data is rare in children .Even if lactic acidosis during asthma is a self-limited condition, it has an impact on assessment and management of respiratory distress. Compensatory hyperventilation of lactic acidosis is often mistaken as a sign of respiratory worsening and leads to inappropriate escalation of bronchodilator therapy, increasing morbidity and mortality , 9.The aim of our study is to describe the prevalence and risk factors contributing to lactic acidosis in children treated with salbutamol for moderate or severe acute asthma.This prospective observational monocentric prevalence study was conducted from May 01, 2017, to April 30, 2019, in a tertiary care children’s hospital.Children and adolescents 2 to 17 years of age hospitalised for acute moderate or severe asthma were eligible for the study. At our institution, patients requiring inhaled b2-agonists minimum every 2 h fill the indications to be admitted, and an initial degree of asthma severity based on PRAM score is part of the clinical evaluation . Exclusi, or in case of secondary appearance of tachypnoea or worsening of the respiratory status during hospitalisation. Oxygen saturation was measured by pulse oximetry before blood extraction. Blood gas assessment including the measurement of pH, pCO2, HCO3, base excess (BE), and glucose and lactate concentrations was performed on a RAPIDPoint500, Siemens, gasometer. One millilitre of blood was used for analysis. Hyperlactatemia was defined as lactate concentration > 2.2 mmol/l. Lactic acidosis was defined as lactate > 5 mmol/l and anion gap (AG) ≥ 16mmol/l (AG = Na + K-HC03-Cl), non-compensated lactic acidosis as pH < 7.35, and lactate concentration as > 5 mmol/l. Compensated lactic acidosis represented lactate concentration > 5 mmol/l, pH ≥ 7.35, and pCO2 < 35 mmHg. Hyperglycaemia was characterised as glucose > 11 mmol/l.Basic clinical data included age; body mass index (BMI); sex; initial degree of asthma severity; dose and type of salbutamol administration, of oral or intravenous steroids, and of inhaled ipratropium bromide; and type of maintenance intravenous fluid. Hypoxemia (defined as SpO2 < 92%) was rigorously assessed and treated. Salbutamol was administered by using a metered dose inhaler (pMDI)  or nebuliser . Three types of maintenance fluid were used: 91% of G10% and 9% of NaCl 10% mix, 91% of G5% and 9% of NaCl 10% mix, or normal saline solution (NaCl 0.9%). Capillary blood sample was drawn 4 h after the first administration of salbutamol in hospitalThe primary outcome was the prevalence of lactic acidosis. Secondary outcomes included other contributing factors like age, sex, BMI, initial degree of severity, salbutamol administered by inhaler or by nebuliser, steroids, ipratropium bromide, and glucose-containing maintenance fluid.Patients older than 11 years and parents or legal guardians were informed orally and in writing about the research project by one of the doctors working in the paediatric emergency room during admission to the hospital. Adolescents ≥ 14 years and their parents or legal guardians provided informed consent. The study was approved by the institutional ethics committee .U test was used to compare the means. We firstly realised simple logistic regression and calculated odd ratio for all potential risk factors. All variables potentially able to influence lactic acidosis (p < 0.2) were used as covariates in multiple logistic regression. Pearson’s correlation coefficient was used to measure statistical relationship between the levels of lactates and doses of salbutamol. All statistical analysis was performed with the Epi Info version 7.2.3.1 software (Centres for Disease Control and Prevention).Categorical data were described as absolute counts. Percentages and continuous data we described as means and standard deviations (SD). The Mann–Whitney Among 627 patients from 2 to 17 years of age hospitalised for moderate or severe asthma, 174 received information about the study. Eleven did not provided informed consent, and 9 did not have blood sample for technical problem. Finally, 154 patients were included in the study . Sex ratio was 1.92 male to female. Forty-three percent of episodes were categorised as severe (PRAM > 8) and 57% as moderate (PRAM 4–8). Salbutamol was administered by pMDI with holding chamber alone in 30% of cases (46/154) or by nebuliser  in 70% (108/154) (Table p = 0.59). Patients with severe asthma received higher doses of salbutamol (mean 19 ± 10.1 mg) compared to patients with moderate asthma (mean 6.67 ± 5.7 mg), p < 0.0005. When delivered by nebulisation , the mean dose of salbutamol was 16 ± 9.3 mg versus 2.4 ± 1.2 mg when delivered by inhaler (1 push = 100 cmg), p < 0.0005.Among 154 patients, 99 (64%) were aged from 2 to 6 years and 55 (36%) were more than 6. A total of 13% were obese  received corticosteroids with a mean dose of 1.85 ± 0.75 mg/kg. Corticosteroids were mainly administered orally (88%). Twenty-three of 154 patients (15%) received ipratropium bromide. Nineteen percent were perfused with glucose-containing maintenance fluid (91% of G10% and 9% of NaCl 10% mix or 91% of G5% and 9% of NaCl 10%)  had mild hyperlactatemia (lactate > 2.2 mmol/l). All of patients with lactate concentration > 5 mmol/l (26%) had lactic acidosis (lactate > 5 mmol/l and augmented anion gap AG ≥ 16 mmol/l). Thirty-four (22%) presented compensated lactic acidosis . Only 6 (4%) had pH < 7.35. None had hypercapnia (pCO2 > 40 mmHg) , as well as between lactic acidosis and severe asthma . When adjusted on potential confusing factors in multivariate analysis, salbutamol administered by nebuliser , age older than 6 years , and hyperglycaemia (aOR = 3.2 95% CI 1.4–7.4) were related to increased risk of lactic acidosis (Table r = 0.17 (SE = 0.24)) . No correlation was found between lactate levels and salbutamol doses (Pearson’s 7 SE = 0.4)  of our patients had increased blood lactate concentration (lactate > 2.2 mmol/l) 4 h after the first salbutamol dose in hospital. Our findings compare to those of Meert who recorded 83% (62/105) of children with mild hyperlactatemia (lactate> 2.2 mmol/l) during status asthmaticus 4 of our . In adul2 < 35 mmHg, and BE < − 7 mmol/l) during acute asthma, with lactate assessment from 7.2 to 9.3 mmol/l 8 to 24 h after admission . None of our patients had known chronic underlying disease. Many authors thought lactic acidosis during asthma to be type B –6. Expos. None ofIn our patients, mean total dose of salbutamol delivered by nebulisation (16 ± 9.3 mg) was almost seven times higher compared to the mean dose delivered by inhalator (2.4 ± 1.2 mg). Higher doses could explain the greater risk of lactic acidosis if salbutamol is administered by nebulisation . According the Cochrane database, other side effects of salbutamol such as increased pulse rate were lower for pMDI in children , as was the risk of developing tremor  . On the Intravenous, oral, and inhaled salbutamol raise glycogenolysis resulting in hyperglycaemia. Concurrent use of corticosteroids may exacerbate blood glucose level . In our We identified other parameters like female sex, severe asthma, and obesity as independent risk factors for lactic acidosis. Even if they could not be confirmed in multivariate analysis, they need to be put forward as our study is the first one to try to identify potential risk factors of lactic acidosis in children with asthma.Our study has some limits. Firstly, only 25% of potential patients with moderate or severe asthma seen in the emergency room were included, which is a major selection bias. Secondly, we performed only capillary lactate assessment. However, prior research suggests that capillary lactate value accurately reflects arterial lactate . MoreoveLactic acidosis is a frequent and early (H4) complication of asthma observed in children treated with high doses of bronchodilators. Salbutamol administered by nebuliser, age more than 6 years, and hyperglycaemia were identified as risk factors of lactic acidosis during asthma. Even if self-limited, this condition is important to recognise to avoid unnecessary and harmful therapeutic intensification.


Critically ill patients are at high risk of developing neurological complications. Among all the potential aetiologies, brain hypoperfusion has been advocated as one of the potential mechanisms. Impairment of cerebral autoregulation (CAR) can result in brain hypoperfusion. However, assessment of CAR is difficult at bedside. We aimed to evaluate whether the automated pupillometer might be able to detect impaired CAR in critically ill patients.We included 92 patients in this retrospective observational study; 52 were septic. CAR was assessed using the Mxa index, which is the correlation index between continuous recording of cerebral blood flow velocities using the transcranial Doppler and invasive arterial blood pressure over 8 ± 2 min. Impaired CAR was defined as an Mxa > 0.3. Automated pupillometer  was used to assess the pupillary light reflex concomitantly to the CAR assessment.p = 0.77). A total of 51 (55%) patients showed impaired CAR, 28 (54%) in the septic group and 23 (58%) in the non-septic group. We found a statistically significant although weak correlation between Mxa and the Neurologic Pupil Index  in the whole cohort as in septic patients ; no correlation was observed in non-septic patients and for other pupillometry-derived variables.The median Mxa was 0.33 in the whole cohort (0.33 in septic patients and 0.31 in the non-septic patients; Automated pupillometry cannot predict CAR indices such as Mxa in a heterogeneous population of critically ill patients. Critical illness is characterized by an acute and severe impairment in vital functions, requiring the admission to the intensive care unit (ICU) to receive specific therapies and an adequate support to the failing organs. Among all the potential causes of ICU admission, sepsis or septic shock is one of the most common and causes millions of deaths and long-term disabilities among survivors each year –4. Multi2), or to local stimuli, such as metabolic activation of the different brain areas. Impaired CAR has been described in brain-injured patients [One of the mechanisms that could promote brain hypoperfusion in this setting is the impairment of cerebral autoregulation (CAR), i.e., the capacity to maintain an adequate and stable cerebral blood flow (CBF) in response to different systemic stimuli, such as changes in arterial pressure of carbon dioxide  or mean arterial pressure (MAP); thus, if the autoregulatory system is overridden, CBF becomes pressure-dependant , 16. ImpAutonomous nervous system dysfunction is evaluated in critically ill patients using different approach, including the heart rate variability; however, pupillary size and pupillary light reflex (PLR) , which aThe aim of this study was therefore to evaluate, whether the PLR assessed by the automated pupillometer could detect impairment of CAR in critically ill patients.We retrospectively analyzed all critically ill adult (> 18 years) patients admitted to the intensive care unit of the Erasme Hospital between January 2017 and March 2019. Patients were eligible if they underwent concomitantly CAR assessment and PLR analysis via an automated pupillometry. Both techniques were performed according to the availability of the devices and to the patient’s condition at the medical round and considered within the common practice. To avoid the effects of long-term ICU stays on the interpretation of the data, only patients admitted since less than 48 h in the ICU were considered. Results of CAR assessment and pupillometry were prospectively reported in the patient data management system (PDMS). Exclusion criteria were pre-existing ocular disease or surgery, previous central nervous system disorders, arrhythmias, being under ECMO therapy, having supra-aortic arteriopathies or the absence of an arterial line for continuous MAP recordings. The local ethics committee approved the study protocol (reference P2019/204) and waived the need for the informed consent.We collected demographic data, comorbid diseases  as well as the Acute Physiology and Chronic Health Evaluation (APACHE) II score on admission. The presence of sepsis, according to standard Sepsis-3 definitions , was recPupillary light reflex was performed using an automated pupillometer, the NeurOptics NPi-200 instrument , which uses an infrared camera that integrates a calibrated light stimulation of fixed intensity (1000 Lux) and duration (3.2 s) to provide rapid measurement (0.05 mm limit) of pupil size and quantitative PLR , constriction velocity, and latency. The measurement is completed in less than 30 s for each eye, and a minimum duration of 1 min was allowed between appraisals of the two pupils to obtain full recovery of baseline pupil diameter after light stimulation. Median values from both eyes were used for comparison with CAR findings. Based on an integrated algorithm, the automated pupillometry calculates the Neurological Pupil Index (NPI), as an index of normal (NPI > 3) vs. abnormal (NPI 0–3) pupillary function. The NPI has the advantage of being minimally influenced by external factors, and in particular is unaffected by opioids and variable individual baseline pupil size . The pupr) represents the strength and direction of a relationship between two variables. It has a value between + 1 and − 1, where 1 represents a total positive correlation, 0 represents no correlation, and − 1 represents total negative correlation. The correlation is considered to be moderately positive when r > 0.3. Given that changes in FV mirror changes in CBF, Mxa > 0.3 means that CBF is dependent on BP changes, and autoregulation is “impaired”; when BP and FV have a negative or weak correlation (Mxa ≤ 0.3), autoregulation is considered intact [Blood pressure (BP) was zeroed at the level of the right atrium ; no correction was made for hydrostatic pressure influence. Transcranial Doppler (TCD) was used to assess blood flow velocity (FV) in the left middle cerebral artery (MCA) using the Doppler Box ; one operator (AQC) performed all TCDs. All recorded signals were digitized via an A/D converter , sampled with a frequency of 50–100 Hz. After a methodological removal of artifacts, we used a custom-written script  to assess autoregulation: BP and FV were then averaged on a 10-s moving window with 50% overlap, and the Pearson correlation coefficient between BP and FV was calculated. The Pearson correlation coefficient between BP and FV is called mean flow index (Mxa). The Pearson correlation coefficient  curves with the corresponding area under the curve (AUC) and related sensitivity and specificity. Statistical analyses were performed using GraphPad PRISM version 5.0 . For all statistical tests, a p < 0.05 was considered significant.Data are expressed as median (25th–75th percentiles) or count (percentage). Comparisons between “impaired” and “intact” CAR with variables from the pupillometer were performed using a Wilcoxon rank test for continuous variables. Comparisons within groups  were also performed. The Pearson correlation coefficient, or Pearson’s On a total of 123 patients undergoing CAR assessment over the study period, 92 had also concomitant pupillometry evaluation and were included in the final analysis. Characteristics of the study population are shown in Table p = 0.72) in the two groups. Median NPI and pupil size were 4.3 and 3.7 mm, respectively; both values were similar between septic and non-septic patients, as for other pupillometry-derived variables  patients had impaired CAR. Mxa was similar between septic and non-septic patients, with a similar number of patients having impaired CAR , although statistically significant , although statistically significant  and the Mxa, which is an index assessing CAR. This correlation remained significant in the septic patients’ group, while no correlation was observed in non-septic patients. Finally, NPI had limited predictive accuracy to identify impaired CAR.2, temperature, and comorbid diseases [The assessment of CAR has been growing in clinical practice, in particular to optimize cerebral perfusion pressure and prevention of secondary brain injury in different acute intracranial conditions, such as traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), ischemic stroke, and post-anoxic encephalopathy –36. Cerediseases –43, manyPupillary size is controlled by the balance between sympathetic and parasympathetic systems, integrated at the midbrain level, as well as by neuronal activity of the locus coeruleus, colliculi, and cingulate cortex . MultiplWhy our hypothesis could not be confirmed by the results of this study? We included a heterogeneous population of critically ill patients; it is therefore possible that diseases inducing both an alteration in cerebral autoregulation and pupillary response would allow a better comparison on the monitoring tools while this would not be possible in others. As such, sepsis is frequently associated with brain dysfunction and impairment of cerebral autoregulation . Few datThis study has some limitations to acknowledge. First, the number of patients included was relatively small in the two subgroups so that the statistical analysis was limited, and no further associative evaluation could be performed. However, it would be unlikely that adding more patients would have changed our conclusions. Second, we did not adjust our findings according to the use and/or total dose of sedatives or analgesics. Although this might have been of interest to eliminate potential bias, the use of automated pupillometry is of particular interest in those patients with an unreliable clinical examination  so that further statistical correction was not considered necessary. Also, the impact of other interesting variables, such as oxygenation, PaCO2, hemoglobin, and body temperature, on the relationship between pupillometry and autoregulation could not be further assessed because of the limited cohort. Third, automated pupillometry does not provide a continuous measurement of pupillary activity, while CAR assessment relies on a continuous recording of BP and FV for several minutes. Fourth, we did not assess the relationship between CAR or pupillometry and outcome; albeit of interest, one single measurement would not be informative in this setting. Further research using repeated measurements would be of interest in the future. Fifth, we dichotomized CAR as intact or impaired using a threshold suggested in previous studies; however, CAR is a continuous phenomenon, and a fixed Mxa value to define its function could have some limitations. Finally, NPI is based on an algorithm that incorporates several quantitative features of the pupillary light reflex; as such, the relationship of each of these components with the autonomic nervous system remains unknown.This study reported a weak association between the cerebral autoregulation and pupillometry-derived variables. These data also suggest that septic patients could be a population where pupillometry might give some information on the autoregulatory capacity of the brain.


Proteinuria, a marker of kidney injury, may be related to skeletal muscle loss. Whether the severity of proteinuria is associated with physical performance is unclear.We examined the association of proteinuria severity with physical performance cross-sectionally in 3357 military young males, free of chronic kidney disease, from the cardiorespiratory fitness and hospitalization events in armed Forces (CHIEF) study in Taiwan. The grades of proteinuria were classified according to one dipstick urinalysis which were collected at morning after an 8-h fast as unremarkable , moderate (2+) and severe (3+ and 4+). Aerobic physical performance was evaluated by time for a 3000-m run and anaerobic physical performance was evaluated by numbers of 2-min sit-ups and 2-min push-ups, separately. Multiple linear regressions were used to determine the relationship.As compared with unremarkable proteinuria, moderate and severe proteinuria were dose-dependently correlated with 3000-m running time : − 0.55, 10.02) and 7.63 , respectively), and inversely with numbers of 2-min push-ups , and − 1.00 , respectively) with adjustments for age, service specialty, body mass index, blood pressure, alcohol intake, smoking, fasting plasma glucose, blood urea nitrogen, serum creatinine and physical activity. However, there was no association between proteinuria severity and 2-min sit-ups.Our findings show a relationship of dipstick proteinuria with aerobic physical performance and parts of anaerobic physical performance in military healthy males. This mechanism is not fully understood and requires further investigations. Protein is one of the major materials such as the actin and myosin components of sarcomere constituting skeletal muscle fibers in the body . Under nThe pathophysiological mechanisms of proteinuria can be reasoned by an increase of glomerular capillary permeability to proteins, reduced protein reabsorption in the renal tubules, and overflow of low-molecular-weight proteins . With reMilitary personnel are a special group of young individuals, required to receive intensive training regularly. We hypothesized that presence of proteinuria in military personnel may be related to skeletal muscle injury caused by rigorous training and thus they have poor exercise performance. In this study, we aimed to investigate the association of proteinuria severity with physical performance in a military population in Taiwan.The study of cardiorespiratory fitness and hospitalization events in armed forces (CHIEF) was performed in eastern Taiwan –20. All 。C, the examinee would be asked to make another appointment while recovery from the sickness to complete the health examination. Anthropometric parameters of body height and body weight were assessed in a standing position of each participant. Body mass index was defined as a ratio of body weight (kilogram) divided by square of height (meter2). Waist circumference was measured at the midpoint between the highest point of the iliac crest and the last palpable rib. All participants measured their blood pressure once over right upper arm in a sitting position following a rest for at least 15 min by an automated blood pressure monitor . Laboratory data of blood biochemical tests for blood urea nitrogen (BUN), serum creatinine and fasting plasma glucose were obtained in the morning after a 12-h fast.Before taking the laboratory examinations, each participant took his temporal temperature and was interviewed by a military physician. If there were any infection symptoms or signs along with the body temperature over 37To avoid a stress status of participants, possibly confounding the interpretation of proteinuria, the urine sample was collected prior to a venous puncture for drawing the blood sample in the morning. Urine proteins were measured using the AUTION dipsticks  by a fully automated urine chemistry analyzer . On the basis of the clinical classifications recommended by the National Kidney Foundation , the conAerobic physical performance was evaluated by 3000-m running time, a strong indicator of the velocity at lactate (anaerobic) threshold . All runN = 2011), moderate  and severe . The characteristics of subjects were expressed as mean ± standard deviation (SD) for continuous data, and numbers with percentages for categorical data. The relationship of moderate and severe proteinuria with the performance in each exercise  were investigated by using analysis of covariance (ANCOVA), and the results were expressed as mean ± standard error (SE). Multiple stepwise linear regression analyses of each exercise performance with moderate and severe proteinuria, relative to unremarkable proteinuria, were also performed as the main analysis. Since the performance in each exercise was centrally distributed .In model 1, age and military service specialty were adjusted. In model 2, body mass index, BUN and serum creatinine were additionally adjusted. In model 3, systolic blood pressure, fasting plasma glucose, smoking status, alcohol intake status and physical activity were further adjusted. These potential confounders for the models were chosen based on prior published associations with physical performance  and thosThe subject characteristics of each group are revealed in Table p < 0.01) and 2-min push-ups numbers  among the unremarkable proteinuria, moderate proteinuria, and severe proteinuria groups after adjusting for all covariates in model 3. However, there were similar 2-min sit-ups numbers among the three proteinuria groups in models 1–3. In addition, since there was only one young female categorized in the moderate proteinuria group, the moderate and severe proteinuria groups were combined to the remarkable proteinuria group in the sensitivity analysis which demonstrated similar tendencies for each physical performance, despite statistically insignificance  and inversely with 2-min push-ups numbers  in model 3. However, moderate proteinuria and severe proteinuria were not correlated with 2-min sit-ups numbers in models 1–3. The sensitivity test for females also showed similar tendencies in each physical performance, despite insignificance in models 1–3  and part of anaerobic physical performance, particularly for muscular endurance of the chest wall and upper extremities in physically fit male adults with euvolemia and without chronic kidney disease, independent of age, body mass index, kidney function, fasting plasma glucose, cigarette smoking, alcohol intake and physical activity. While the effect sizes may be small, the results are still concerning given the young age and general good health of the study population, especially because proteinuria is suspected to worsen over time.Previous studies have revealed that there was an association between muscle wasting and a decrease of renal function. People with chronic kidney disease are predisposed to muscle wasting and vice versa, those with sarcopenia have a decrease of glomerular filtration rate, which may progress to chronic kidney disease status and result in presence of persistent proteinuria –32. Our The other important findings were that higher prevalence of higher fasting plasma glucose levels and cigarette smoking were observed in those with moderate or severe proteinuria. As is known, exercise induced proteinuria has been associated with higher insulin resistance  which inOur study had several advantages. First, the laboratory examinations and the procedures of exercise tests were all performed standardly. Second, a large number of military males were included for the analysis which could provide sufficient power detecting the difference between the groups. Third, 91.5% of the male participants were retained in the analysis that the selection bias would be minimized. Fourth, the daily schedule of military such as training program was unified so that the bias from unmeasured confounders could be controlled at baseline. However, there were several weak points in this study. First, the presence and grades of proteinuria were measured only by one urine dipstick test, which was easily influenced by many physiological and environmental conditions . Second,Our findings show a dose-dependent relationship of dipstick proteinuria with aerobic physical performance and part of anaerobic physical performance in military healthy males free of chronic kidney disease. Cigarette smoking and increased insulin resistance may play a potential role on the relationship between remarkable proteinuria and muscle wasting, leading to impaired physical performance. This mechanism is not fully understood and requires further investigations.Additional file 1.Additional file 2.