We aimed to explore whether the aforementioned factors introduce noise into the signal, and discuss several approaches to reduce this noise. Methods: Study in mechanically-ventilated ICU patients. Exhaled breath was monitored using a continuous eNose with metal oxide sensors. Linear (mixed) models were used to study hypothesized associations. Results: In total, 1251 h of eNose data were collected. First, the initial 15 min of the signal was discarded. There was a negative association between humidity and Sensor 1 (Fixed-effect β: −0.05 ± 0.002) and a positive association with Sensors 2–4 (Fixed-effect β: 0.12 ± 0.001); the signal was corrected for this noise. Outliers were most likely due to noise and therefore removed. Sensor values were positively associated with end-tidal CO2, tidal volume and the pressure variables. The signal was corrected for changes in these ventilator variables after which the associations disappeared. Conclusion: Variations in humidity, ventilator disconnections, nebulization of medication and changes of ventilator settings indeed influenced exhaled breath signals measured in ventilated patients by continuous eNose analysis. We discussed several approaches to reduce the effects of these noise inducing variables.Introduction: Continuous breath analysis by electronic nose (eNose) technology in the intensive care unit (ICU) may be useful in monitoring (patho) physiological changes. However, the application of breath monitoring in a non-controlled clinical setting introduces noise into the data. We hypothesized that the sensor signal is influenced by: (1) humidity in the side-stream; (2) patient-ventilator disconnections and the nebulization of medication; and (3) changes in ventilator settings and the amount of exhaled CO Analysis of exhaled breath has received increasing attention over the last years as a potential diagnostic tool for a variety of diseases. Several technologies are available for breath analysis . Gas chr2 monitoring in exhaled air [2.Intensive care unit (ICU) patients are per definition severely ill and their physiology is easily disturbed, which makes their clinical condition highly unstable. Therefore, there is a need for continuous monitoring, as is standard of care for several physiological parameters such as pulse oxymetry and end-tidal COaled air ,21. The aled air , but so Intubated and mechanically-ventilated ICU patients, expected to remain mechanically-ventilated for at least 48 h, were eligible for this study. Additionally, patients had to be older than 18 years. Patients were excluded when they were not expected to survive for a considerable amount of time. The Institutional Review Board of the Academic Medical Center, Amsterdam, The Netherlands concluded that the legislation on human participation in research was not applicable because of the non-invasive, non-interventional nature of the study.2O, nebulization of acetylcysteine and salbutamol, and a pulmonary toilet including suction of secretions every 6 h. In addition, a heat-moist exchanger was placed in the circuit and active humidification was not used routinely. Mechanical ventilators from several vendors were used. Arterial blood gas measurements were taken on indication, with a minimum of 3 measurements per day. These factors, and other aspects of clinical care were not influenced by study procedures.Standard of ventilatory support for intubated and mechanically-ventilated patients on the ICU of the Academic Medical Center in Amsterdam included, but was not limited to: Pressure Support or Pressure Controlled mode of ventilation, tidal volume of 6–8 mg/kg predicted body weight, a level of Positive End Expiratory Pressure (PEEP) ≥5 cm HExhaled breath was monitored in patients of the mixed medical/surgical ICU of the Academic Medical Center in Amsterdam, the Netherlands using a continuous eNose adapted for clinical use in the intensive care unit . The sensor array contained 4 different metal oxide sensors , which were chosen for their stability, clinical potential, performance and because they were widely used ,23,24. TData analysis was performed using R version 3.2.4 .Noise inducing variables in the data were identified by plotting data for visual inspection by the investigators. Changes occurring concurrently in both sensor signals and variables were noted. The major noise inducing variables are plotted in The sensors of the eNose have to adapt to the changing substances in the air when connecting an eNose to a subject. The left panel in The humidity in side-stream connector leading to the eNose may cause a change in the sensor response, unrelated to the actual VOC profile B. The asAfter correcting for humidity, outliers, particularly those due to intermittent disconnections and nebulization of medication, were removed. As short periods of extreme values are most likely to be erroneous, we chose to discard the top and bottom 2.5% of the measurements. This removes the most prominent peaks and dips. Then, a LOESS smoother with default settings was calculated, after which the relative error between the signal and the smoother was computed. When this relative error was above a set threshold at a point in the data, this data point was replaced by the value of the LOESS smoother. Finally, to illuminate the worst jitter, the signal was smoothed using a LOESS smoother, with a span of 30 observations.2 (ETCO2), changes in tidal volume, inspiratory pressure, peak pressure and PEEP. Backwards variable selection was used to eliminate non-significant effects. Finally, a LOESS smoother with a span of 15 observations was used once more to correct for jitter introduced after ventilator variable correction.Changes in ventilation settings could have a big influence on the eNose signal. It can be imagined that a change in tidal volume, PEEP or minute volume may influence the abundance of measured VOCs. Ventilation settings stored in the PDMS were used to correct for this phenomenon. A similar strategy as used for correcting for changes in humidity was followed. However, instead of a linear regression model, a mixed model with the patient number as random effect was used. We investigated the available relevant variables: changes in minute volume, changes in end tidal COBetween October 2012 and July 2015, 1251 h of eNose data were collected in 23 different patients. Patient characteristics are shown in The first fifteen minutes of sensor signal was discarded to allow the sensors to adapt to the new circumstances. A shorter period did not result in a steady state in all patients. The middle and right panels in r between humidity and eNose sensors for each patient can be found in The middle and right panel of 2, tidal volume and the variables. A matrix with mean correlation values between ventilator readings and sensors of all patients in our study is shown in The presented results suggest that humidity, ventilator disconnections, nebulization of medication and ventilator settings indeed influenced exhaled breaths signal measured in ventilated patients by continues eNose analysis. We described several approaches to reduce these types of noise. This implies that direct translation of breath analysis technology developed for singular measurements is impossible; the signal should be corrected in a multi-step fashion to remove noise that correlates with variations in patient care that are not directly linked to the (patho) physiological process of interest.2 [This influence on the signal is explained by the following considerations. First, the commonly used metal oxide sensors that we also used in this study are known to be influenced by humidity ,28. Ther2 .Several strengths of this study should also be noted. First, correcting for confounding factors was possible because we recorded data systematically in a database at one-minute intervals. Therefore, distilling the actual underlying eNose signal was possible. Second, the long observation periods per patient ensured that we measured a large number of possible sources of noise. Third, the sensor array that has been used was shown to discriminate between asthmatics, COPD patients, lung cancer patients and healthy controls . TherefoThe described steps to remove noise inducing variables from eNose signals is a first step towards continuous breath monitoring in a clinical setting. In addition, continuous monitoring of biological markers allows for trend analysis, which is impossible with infrequent blood draws. Next to monitoring systemic markers, investigating molecular processes in the lung can possibly be simplified by monitoring exhaled breath. Currently, this is only possible by performing a bronchoalveolar lavage, which is considered to be very invasive. Diagnostic accuracy, however, should be studied and will be reported separately. Our findings help other researchers in their analysis, and interpretation of their results is beneficial to developers of eNose technology.To conclude, changing humidity influenced eNose sensors and sensor signals were corrected. After outlier removal and smoothing, the signal was corrected for changes in ventilator settings. Pre-processing is the first step toward using continuous monitoring of exhaled breath.


P < 0.001). The response in the parafoveal region was greater than that in the peripapillary region (P < 0.001), and was age-dependent . Foveal avascular zone area detectable with OCTA significantly increased from baseline by 6.63% during VM-IV (P < 0.05). Autoregulatory responses to a VM did not show gender-related differences in either retinal region. The autoregulation of retinal vessels may vary in different regions of the fundus. Optical coherence tomography angiography could be a useful method for evaluating the autoregulation of the retinal vascular system.The impairment of retinal vascular autoregulation can be an early manifestation of many systemic and ocular diseases. Therefore, quantifying retinal vascular autoregulation in a non-invasive manner is very important. This study evaluated the effects of a Valsalva maneuver (VM)-induced blood pressure increases on retinal vascular autoregulation. Parafoveal and peripapillary retinal vessel density were measured with optical coherence tomography angiography before (baseline) and 5 s after each subject completed a VM (Phase IV [VM-IV]). Hemodynamic parameters and intraocular pressure (IOP) were examined. Blood pressure  and ocular perfusion pressure significantly increased during VM-IV, but IOP and heart rate (HR) did not change. The VM-induced blood pressure overshoot significantly decreased parafoveal (8.43%) and peripapillary (1.57%) perfused retinal vessel density (both  Retinal vessel autoregulation is a complex homeostatic process that keeps blood flow constant during changes in blood pressure  is performed by moderately exhaling against a closed airway. The VM is frequently performed during daily activities, including heavy lifting, vomiting, straining, forceful coughing, and sneezing. Compared with other methods for changing BP, the VM is a simple way to transiently increase BP . More specifically, this study examined the effect of BP changes on the retinal microcirculation during VM-IV in healthy subjects.This study protocol was reviewed and approved by the institutional review board of the Eye, Ear, Nose, and Throat (EENT) Hospital of Fudan University . All study conduct adhered to the tenets of the Declaration of Helsinki and written informed consent was obtained from all subjects.Healthy subjects who visited the EENT Hospital of Fudan University for a routine health screening were asked to participate in this study. Only the right eye of each subject was included in analyses. The inclusion criteria were: a best-corrected visual acuity (BCVA) of at least 16/20; no history of elevated intraocular pressure ; an axial length (AL) of 21–25 mm; and a spherical equivalent (SE) between −3 and + 1 D. The exclusion criteria were: a history of systemic disease, such as hypertension, diabetes mellitus, or cardiopulmonary insufficiency; the use of systemic or topical medication within the preceding 1 month; a history of intraocular disease, ocular surgery, or trauma; clinically relevant media opacities; and an inability to correctly perform a VM.All study subjects underwent a thorough ophthalmologic examination, including slit-lamp biomicroscopy, an undilated fundus examination , and measurement of refractive error , BCVA, IOP [with a Topcon CT-80A Computerized Tonometer ], and AL . The SE of the refractive error was used in data analyses and was defined as the spherical error plus one-half of the cylindrical error.The subjects were asked to sit and breathe normally for 20 min. The baseline OCTA scans were then performed with a spectral domain system  , then were taught to do a modified VM, as previously described  peripapillary area  and foveal avascular zone (FAZ) area.All OCT angiography images were obtained using a commercially-available spectral-domain OCT system, as described in Section Study Examinations. t-tests. The correlation between the independent variables age, sex, baseline BP, variation in BP, variation in OPP, and variation in MAP during VM-IV, with perfused vessel density response to VM as the dependent variable were analyzed using a linear regression model. All analyses were performed using SPSS statistical software  and statistical significance was defined as p < 0.05.Data are presented as mean ± standard deviation. Systemic parameters, IOP, FAZ, and retinal perfused vessel density before and after subjects performed a VM were compared using paired A total of 109 healthy volunteers  were included in this study. Mean subject age was 44.91 ± 10.10 years (range: 19–61 years). Mean SD was −0.23 ± 0.98 D (range: −3.0–1.0 D), mean AL was 23.14 ± 0.78 mm (range: 21.51–24.84 mm), and mean baseline IOP was 12.62 ± 2.45 mmHg (range: 9–21 mmHg).p < 0.001). However, IOP (p = 0.411) and HR (p = 0.304) did not significantly change.Measurements of BP, HR, MAP, IOP, and OPP before and during VM-IV are summarized in Table p < 0.001) and 1.57% ± 3.98% (p < 0.001), respectively .Table p < 0.001, Table p = 0.295) or peripapillary  region .Linear regression analyses revealed a significant negative correlation between age and the parafoveal perfused vessel density response during VM-IV  and the change in BP. The following factors might explain this result. First, although the increase in BP induced by VM-IV caused a reduction in the average vessel density, the standard deviation for this change was relatively large. This indicates that the capacity for retinal vascular autoregulation (the BP response induced by VM-IV) differs among healthy individuals, so the percentage change in vessel density per unit increase in BP is unclear. Second, OCTA images only show the retinal vessel density, and not the retinal blood flow. Consistent with our results, Jeppesen et al.  reportedOur study had several limitations. First, IOP and perfused retinal vessel density could not be simultaneously monitored during VM-IV. Thus, subjects were required to perform the VM twice; once to measure IOP changes and once to measure retinal vascular changes. While BP was measured only during the first VM procedure, this likely increased measurement error and reduced OPP measurement accuracy. However, the current and prior studies (Polska et al., This study combines a classic method for elevating BP with a novel technique to evaluate regional retinal microvasculature autoregulation. Our OCTA measurements show that BP changes during VM-IV induce a significant reduction in retinal perfused vessel density in both the parafoveal and peripapillary regions. Furthermore, changes in retinal perfused vessel density are negatively correlated with age in the parafoveal region.CJ and XK designed of the work, modified the paper; YZ and HX did the data acquisition and wrote the paper; JY and YH did the data analysis; XS modified the paper.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.


Melatonin administration to high cholesterol-treated and high fat-treated rats has been shown to suppress body weight and visceral adiposity. In addition, in various animal models related to obesity, metabolic syndrome, and diabetes, melatonin has beneficial efficacy in ameliorating various metabolic symptoms, including attenuating weight gain, lowering blood pressure (BP), and improving insulin resistance. This systematic review aims to investigate whether melatonin or melatonin agonists significantly attenuate metabolic side effects among psychiatric populations treated with atypical antipsychotics.Four randomized controlled trials were identified through a comprehensive literature search using MEDLINE, EMBASE, and the Cochrane Library on 22 October 2015. These four trials (including three melatonin studies and one ramelteon study) included 138 patients, of whom 71 were treated with melatonin or ramelteon and 67 were treated with a placebo. Because of high heterogeneity, we did not carry out a meta analysis.Melatonin was beneficial in lowering blood pressure among bipolar disorder patients; this blood pressure-lowering effect was not prominent among schizophrenic patients. Melatonin appeared to improve lipid profiles and body composition and attenuated weight gain among both schizophrenic and bipolar disorder patients. Ramelteon showed a significant efficacy in lowering total cholesterol level.Despite the few studies included, this systematic review provided promising evidence of the potential benefits of melatonin and its agonists in attenuating one or more components of metabolic syndrome among psychiatric patients using atypical antipsychotics.


Systemic arterial hypertension manifests as constant elevation of blood pressure and is considered to be an important cardiovascular risk factor. Systemic evaluation of cardiovascular diseases in patients with systemic arterial hypertension is imperative for prevention.The objective of the present study was to investigate and inter-relate sex and age with systemic arterial hypertension and cardiovascular diseases.Medical records of patients with systemic arterial hypertension and cardiovascular disease were evaluated. Data from the medical records were recorded in a prescribed protocol and the data were analyzed and correlated to the patients’ age and sex.A total of 170 medical records for patients who visited the cardiology department were reviewed. Of these, 50 patients had systemic arterial hypertension and 19 of this subset had cardiovascular diseases. When we correlated systemic arterial hypertension with age, we observed that patients in the 51-60 years age group were more prone to systemic arterial hypertension (36%). Most of the patients with both systemic arterial hypertension and cardiovascular disease were female and in the 61-70 years age group, while among males the highest rate of occurrence was seen in the 51-60 years age group. The correlation coefficient (r) was 0.62, indicating a moderate, positive, linear relationship between systemic arterial hypertension and cardiovascular disease.A majority of patients with systemic arterial hypertension may develop cardiovascular disease and, as age increases, the tendency to develop hypertension also increases. It usually means arterial pressure, which is recorded in millimeters of mercury – for example 120/80 mmHg. The higher number denotes the systolic pressure while the lower number denotes the diastolic pressure.Both prevalence and incidence of CVD are increasing in the developing world.The objectives of this study were therefore to investigate the occurrence of CVD in patients with SAH from a South Indian population, by retrospective evaluation, to investigate the relationships between sex, age, and SAH, and to inter-relate these factors with CVD.This retrospective study was conducted at the Dr. T.M.A Pai Hospital, a primary tertiary care teaching hospital in Udupi district of Karnataka state, India. Human research ethics committee clearance was obtained prior to data collection (IEC 322/2015). Medical records from the past five years for patients with SAH who had CVD were collected from the medical records section of the hospital. Patients’ details were kept confidential and prior permission was obtained from the patients and their families. No interventions were performed. All relevant clinical and laboratory data was documented on a prescribed protocol. Patients’ demographic data, duration of hospital stay, type of CVD, whether or not they had diabetes, and smoking and drinking habits were noted. All relevant information was noted from eligible patients’ files based on the inclusion and exclusion criteria . A totalThe data collected were classified according to whether or not patients had SAH. Records for patients who had SAH and CVD were then selected and analyzed. They were then correlated to patient age and sex. A Spearman correlation coefficient [r] was calculated using the values of the two variables (SAH and CVD) to determine whether they were associated. The data were analyzed using SPSS (version 16.0) software.Of the total of 170 cases, 50 patients had SAH (29%) without any other illnesses diagnosed that are not related to cardiology and all were more than 20 years old. We excluded other records because the patients had SAH associated with other diseases. Of the remaining 50 patients, 27 were female and 23 were male.Nineteen of the patients with SAH had CVD (38%), while 31 of them did not have any CVD (62%) associated with SAH . This shWhen we related SAH to sex we observed that the prevalence was higher among females (54%) than among males (46%). Most of the female patients with SAH and CVD were in the 61-70 years age group, while among males the highest rate of occurrence was seen in the 51-60 years age group. The lowest frequency was seen in the 21-40 years age group .The Spearman correlation coefficient (r) for incidences of SAH and CVD showed a moderate, positive, linear relationship (r=2). This clearly indicates that SAH and CVD are significantly related to each other, which is a very important finding.Systemic arterial hypertension is diagnosed based on elevation of either systolic or diastolic blood pressure and the objective of hypertension management is to attain normalization of both. There is a strong and frequent association between SAH and CVD. Cardiovascular diseases are diseases in which several factors such as smoking, dyslipidemia, SAH, DM, obesity, and hereditary factors play major roles. According to reports, cardiovascular deaths cause 34% of global mortality in women and 28.2% of all deaths in men and are affect all sections of the society.Systemic arterial hypertension is considered to be a major risk factor in recent years since patients with SAH have two times greater chances of getting CVD. In clinical practice, treatment of high blood pressure is focused on achieving health benefits for patients, whereas public health is focused on prevention of high blood pressure and to reduce the incidence of coronary heart disease in populations.In terms of its relation to sex, while men are said to be predominantly affected by SAH, women are also no longer considered immune to its occurrence.,In recent years, infectious diseases have become relatively less of a concern, while chronic diseases like CVD continue to plague the global population. It has also been noted that most of these diseases are largely related to lifestyle factors, and can be minimized or prevented by lifestyle changes. This would be the most appropriate method to deal with SAH and CVD-related mortality and morbidity. Several evidence-based studies have constantly indicated a positive correlation between physical activity and good health. People who tend to have sedentary lifestyles risked an increase in blood pressure over time, whereas those who were physically active seemed to avoid this adverse effect.The present study revealed that there exists a positive and significant relationship between CVD and SAH and that SAH is a major risk factor of CVD.


P = 0.013), which was in agreement with the results of IPTW analysis . The risk of composite outcomes was higher in RAS blockade users in IPTW , but was marginal significance in PS matched analysis . The habitual use of RAS blockades in pre-dialysis patients with advanced CKD may have a detrimental effect on renal outcome without improving all-cause mortality. Further studies are warranted to determine whether withholding RAS blockade may lead to better outcomes in these patients.Renin-angiotensin-system (RAS) blockade is thought to slow renal progression in patients with chronic kidney disease (CKD). However, it remains uncertain if the habitual use of RAS inhibitors affects renal progression and outcomes in pre-dialysis patients with advanced CKD. In this multicenter retrospective cohort study, we identified 2,076 pre-dialysis patients with advanced CKD (stage 4 or 5) from a total of 33,722 CKD patients. RAS blockade users were paired with non-users for analyses using inverse probability of treatment-weighted (IPTW) and propensity score (PS) matching. The outcomes were renal death, all-cause mortality, hospitalization for hyperkalemia, and interactive factors as composite outcomes. RAS blockade users showed an increased risk of renal death in PS-matched analysis (hazard ratio [HR], 1.381; 95% CI, 1.071–1.781;  The use of renin-angiotensin system (RAS) blockers such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are first-line options for reducing proteinuria and slowing the progression of nephropathy in diabetic patients. Moreover, RAS blockers are the antihypertensive drugs of choice in patients with non-diabetic chronic kidney disease (CKD) –4. TheseAlthough it is widely accepted that RAS blockades have specific renoprotective effects in CKD patients, the supporting evidence is not definitive. Indeed, a number of rigorous analyses of major studies have questioned the protective effects of RAS blockade, and noted several uncertainties –19. In aMost of large-scale clinical trials supporting the use of RAS blockades were principally conduced in populations comprising middle-aged individuals who had preserved renal function or mild to moderate renal insufficiency (CKD stage 1 to 3). Although there were previous studies that included severe renal insufficiency (CKD stage 4) , 27, notThere is uncertainty regarding the risks and benefits associated with the use of RAS blockade in patients with advanced CKD (stage 4 or 5). Therefore, this study assessed the effects of habitual use of RAS blockers on the risk of initiation of renal replacement therapy (RRT) and/or death and hospitalization.2 using the modification of diet in renal disease [MDRD] study equation) were selected [This was a retrospective propensity score (PS)-matched study on the effects of RAS blockers on renal outcomes and/or death in pre-dialysis patients with severe advanced CKD (stage 4 or 5). The data used were from adults aged ≥19 years who presented to one of four tertiary hospitals—Gachon University Gil Medical Center , Cheju Halla General Hospital , Chosun University Hospital , and Chungbuk National University Hospital —with renal problems between November 1999 and December 2014. Initially, a total of 33,722 CKD patients were identified, and 3,239 subjects with stage 4 or 5 CKD (eGFR <30 mL/min/1.73mselected . From th-1.154×(age)-0.203×0.742  [Demographic, clinical, and laboratory data were obtained by review of electronic medical records. The demographic and clinical data included age, sex, with or without nephrology care, medications, and medical comorbidities . Diabetes and hypertension were identified using the validated ICD-10 codes. CVD was defined as angina pectoris, myocardial infarction, other ischemic heart disease, atrial fibrillation, heart failure, or cerebrovascular disease. Information about medications included antihypertensive medications including RAS blockers (ACEI/ARB), calcium-channel blockers (CCBs), beta-blockers, diuretics, and statins. The laboratory data included the magnitude of proteinuria and serum levels of creatinine, hemoglobin, albumin, calcium, and phosphorus. Proteinuria was measured by the dipstick test and was defined as negative, trace, or greater. GFR was estimated using the original four-variable MDRD equation as follows: eGFR = 186 × (serum creatinine) female) .The primary outcome of interest was the development of ESRD that required long-term dialysis, and the secondary endpoint was the composite outcome . The onset of ESRD was defined as the date of initiation of long-term dialysis (≥ 3 months), and the onset of the composite outcome was the date of initiation of long-term dialysis or death or hospitalization, whichever came first.t-test, and categorical variables were compared using the χ2 test or Fisher’s exact test, as appropriate, prior to PS matching. To reduce the impact of selection bias and potential confounding factors due to differences in patient characteristics associated with treatment allocation in a non-randomized observational study, rigorous adjustment for differences in baseline characteristics was performed using inverse probability of treatment-weighted (IPTW) and PS-matched analyses. The PS of all of the subjects was estimated by modeling the probability of receiving RAS blockade. To determine the probability of receiving RAS blockade, a multivariable logistic model was constructed with the following covariates: age, sex, nephrologist visit, diabetes, hypertension, CVD, eGFR, proteinuria, serum levels of hemoglobin, albumin, calcium, phosphorus; and use of CCBs, beta blockers, diuretics, or statins. Using the multivariable logistic model, a PS was calculated for each individual. Subsequently, the derived PS values were used to match ACEI/ARB users with non-users at a ratio of 1:1 using the greedy matching algorithm. Following PS generation, weights of patients were calculated for IPTW analysis; weights for ACEI/ARB users were the inverse of those for PS and weights for non-users were the inverse of (1-PS). If the distribution of PS is highly variable, the treatment pattern will have extremely large weights [t-test and McNemar test for continuous and categorical variables, respectively. The Kaplan-Meier method was applied to estimate the unadjusted cumulative incidence of primary and composite outcomes, and a log-rank test was used to assess differences between the groups. A Cox’s proportional hazard regression was performed to estimate adjusted hazard ratios (HRs) of ACEI/ARB use with 95% confidence intervals (CIs) for the incidence of ESRD and the composite outcome. The adjusted covariates used in the Cox regression were as follows: age, sex, nephrologist visit, diabetes, hypertension, CVD, eGFR, proteinuria, serum levels of hemoglobin, albumin, calcium, phosphorus; and use of CCB, beta-blockers, diuretics, or statins. Two-sided P values are reported, and a P value < 0.05 was considered statistically significant. PS matching was performed with the SAS software package ; other analyses were performed using the SPSS Statistics software package .For data description, continuous variables with a normal distribution were expressed as means ± standard deviation (SD), and categorical variables as frequencies and percentages. Continuous variables were compared using Student’s  weights . Therefo weights –32. The A total of 2,076 patients with advanced CKD (stage 4 or 5) met the inclusion criteria and were included in the analyses. The demographic and clinical characteristics of the study population are shown in P < 0.001; P = 0.075). However, the rate of hospitalization for hyperkalemia was higher in ACEI/ARB users than in non-users (P = 0.042). In addition, use of ACEI/ARB was significantly associated with a greater risk of developing the composite outcome of ESRD or death from any cause or hospitalization for hyperkalemia  was significantly higher in ACEI/ARB users compared to non-users, but the adjusted HR for the composite outcome was not different between the two groups  and 28 months , respectively. During the observation period, a total of 631 (30.4%) patients developed ESRD requiring long-term RRT, and 257 (12.4%) patients died. ACEI/ARB users had a significantly higher risk of developing ESRD compared to non-users (P = 0.837 and P = 0.302). However, the risk of composite outcome was significantly increased in ACEI/ARB users compared to non-users , which was consistent with the findings following IPTW adjustment . The adjusted HR for the composite outcome of ESRD or death from any cause or hospitalization for hyperkalemia was higher in ACEI/ARB users than in non-users, but did not reach statistically significant levels  in the PS-matched analysis. However, IPTW adjustment resulted in a significantly increased risk of composite outcome . Additional analysis performed among the three groups , ACEI or ARB users showed similar patterns, but ACEI+ARB users did not show significant different outcomes compared with non-users , the use of ACEI/ARB was associated with an increased risk of developing ESRD, necessitating long-term dialysis and the composite outcome of ESRD or death from any cause, or hospitalization for hyperkalemia. After controlling for potential confounding factors using PS matching and IPTW, the findings suggested an increased risk of ESRD, but no difference in all-cause mortality, in ACEI/ARB users compared to non-users. This suggests that the use of RAS blockers in this patient population may accelerate progression to ESRD without enhancing survival.et al. [et al. [Our findings are not in agreement with the pre-existing belief that the use of RAS blockers has favorable effects on renal outcomes. Numerous studies have shown that RAS blockade using an ACEI or ARB slowed the rate of renal progression –11, whicet al.  reportedet al. . Third, et al. . Similar [et al. , 37.et al. [2) than those of the study , because we included patients with CKD stage 5 (42.3%) as well as CKD stage 4 (57.3%). Moreover, we included diabetic patients while they included only non-diabetic patients. In addition, recently, Hsu et al. [Hou et al.  demonstru et al.  conducteu et al. –41. ThusThe mechanisms underlying the association of RAS blockade with an increased risk of renal failure in advanced CKD patients is unclear. Possibilities include the fact that the prevalence of CKD increases with age, and all of the stages of CKD are more prevalent at older ages , 43. ThuThis study investigated the effects of RAS blockade in pre-dialysis patients with advanced CKD, who had been excluded from the majority of previous studies. Moreover, a relatively large number of patients with stage 4 or 5 CKD at multiple centers was included. However, this study had several limitations. First, this was an observational study; thus, it had the inherent drawback of random allocation to a treatment group (users of RAS blockers) or non-treatment group (non-users of RAS blockers), which could lead to selection bias. To reduce such bias and minimize differences in the baseline characteristics between the two groups, IPTW and PS-matched analyses were performed. However, this is an imperfect substitute for a randomized study and can result in hidden bias due to differences in unmeasured covariates. In addition, the causality of the results could not be inferred due to the study design. Second, the present study is not feasible to assess the change in blood pressure and proteinuria according treatment due to an uncontrolled study design, but blood pressure and proteinuria are known to be important risk factors for renal outcome. The change in blood pressure and proteinuria might contribute to confounding effects on the use of RAS blocker and renal outcome. Third, previous studies have shown that adding mineralocorticoid receptor antagonist (MRA) to ACEI and/or ARB reduced in proteinuria and blood pressure, even though whether it prevents renal progression is unknown , 56. In In conclusion, ACEI/ARB treatment in pre-dialysis patients with advanced CKD may have detrimental effects on renal outcome without improving all-cause mortality. Further studies are warranted to determine whether withholding ACEI/ARB treatment leads to improved outcomes.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.S5 Table(DOCX)Click here for additional data file.S6 Table(DOCX)Click here for additional data file.


The aim was to investigate whether mild kidney dysfunction and low-grade inflammation in post-myocardial infarction patients are independently associated with markers of mental well-being .In post-myocardial infarction patients, kidney function was assessed by estimated glomerular filtration rate (eGFR) calculated from the combined CKD-EPI formula based on serum levels of both creatinine and cystatine C. Systemic inflammation was assessed using high sensitivity C-reactive protein (hs-CRP) levels. The 15-item Geriatric Depression Scale (GDS-15), the 3-item apathy subscale and the 4-item optimism questionnaire (4Q) were used to measure mental well-being and were analyzed using linear multivariable regression analysis.p < 0.001), more apathy symptoms , and less dispositional optimism . Moreover, higher levels of hs-CRP were associated with more depressive symptoms , more apathy symptoms  and less dispositional optimism (β = -0.047 p = 0.024). Apathy showed the strongest independent relation with both low eGFR and high hs-CRP.Of the 2355 patients, mean age was 72.3 (range 63–84) years and 80.1% were men. After multivariable adjustment, a poorer kidney function was associated with more depressive symptoms (β = -0.084, In post-myocardial infarction patients, impaired kidney function and systemic inflammation showed a stronger association with apathy than with depressive symptoms and dispositional optimism. Depressive symptoms in coronary heart disease (CHD) patients are associated with an increase in cardiac morbidity and mortality . The pre2) had more depressive symptoms than those without CKD (eGFR ≥ 60 ml/min/1.73 m2). However, in only one of those studies (that included patients with diabetes) did the increased risk of depressive symptoms remain significant after adjustment for all relevant covariates [2 or higher) are associated with more depressive symptoms is still largely unknown. Moreover, the largest study that analyzed the continuous relation between eGFR and depressive symptoms found no significant associations [In three large cross-sectional studies, including 3700 to ≥ 28,000 patients –16, thosvariates . Whetherciations . Moreoveciations . In contciations .A low-grade pro-inflammatory state is common in patients with CHD, exemplified by higher levels of serum C-reactive protein (CRP) . A positThe association between depressive symptoms and CHD has been called into question by recent cross-sectional and prospective studies in community-dwelling elderly –26. ApatThe Alpha Omega Trial provided us with the opportunity to perform a cross-sectional analysis of mental well-being in post-myocardial infarction patients with a kidney function that ranged from normal to non-dialysis-dependent CKD stage 5. We aimed to investigate whether mild kidney dysfunction and low-grade inflammation were independently associated with markers of mental well-being i.e. depressive symptoms, apathy symptoms, and dispositional optimism. Dispositional optimism is defined as generalized positive outcome expectancies and a future orientation with trait-like mental properties .Whereas previous studies used only creatinine levels to assess the eGFR, we included both creatinine and cystatin-C (CysC) levels to more accurately estimate kidney function , as wellThe Alpha Omega Trial was a multicenter, double-blind, placebo-controlled trial conducted between 2002 and 2009 on the effect of low doses of n-3 fatty acids on cardiovascular events, described in detail elsewhere , 33. TheFor the present cross-sectional study we used the 40-month follow-up data of 2355 (48.7% of 4837) patients who supplied blood samples and also completed the mental well-being questionnaires at 40 months .n = 206 of 2355, 8.7%).Depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS-15) . This sen = 73 of 2355, 3.1%).Apathy was assessed using the GDS apathy-3 subscale. This is a subscale of the GDS-15 which consists of the following three questions: “Have you dropped many of your activities and interests?”, “Do you prefer to stay at home, rather than going out and doing new things?”, and “Do you feel full of energy?” Compared with the 14-item apathy scale , the GDSn = 21 of 2355, 0.9%).Dispositional optimism was assessed using the 4Q which centers around a focus on the future and is more closely related to life engagement, vitality, and feelings of having a purpose in life. In the Netherlands, the 4Q was used as part of a national ‘life situation’ survey by the Central Bureau of Statistics in 1976 and 1982. The 4Q consists of the following four items “I still expect much from life,” “I do not look forward to the years to come,” “My days seem to pass by slowly,” and “I am still full of plans” (our translations). The response format was a 3-point scale of frequency: “fully in agreement” , “partially in agreement” , and “not in agreement” . The additional answer category “do not know” was also coded as the midpoint . The scores of two questions needed to be reverse coded, so that higher scores indicated greater optimism. Higher scores (range 0–8) indicated higher dispositional optimism. The 4Q shows moderate internal consistency and has clinical predictive value for cardiovascular mortality . For comBlood handling procedures for the Alpha Omega Trial are described in detail elsewhere . In brien = 82) and, therefore, not reported in accordance with the Standard Operating Procedure of the central laboratory.Serum creatinine and CysC were measured from stored blood samples in a central laboratory . Serum cSerum CysC was measured by means of a particle-enhanced immune nephelometric assay . We used calibrators and assays of the same lot code, which was stable (no downward drift). CysC was calibrated directly using the standard supplied by the manufacturer  . The anaWe estimated GFR using the combined creatinine-CysC-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation from 2012, taking into account age, sex, and race . In addiSerum hs-CRP was measured in stored serum samples . Intra- and inter-assay variation for low hs-CRP (mean = 1.0 mg/l) was 2.1 and 1.6%, respectively, and for high hs-CRP (mean = 2.8 mg/l) this was 2.0 and 2.4%, respectively.2) and blood pressure was measured. Diabetes mellitus was considered present in the case of a self-reported physician diagnosis, use of antidiabetic drugs, and/or elevated blood glucose.Patients were interviewed and physically examined by trained research nurses at home or in the hospital. Information on demographic variables , lifestyle habits , medication use and medical history  were collected by self-administered questionnaires, as previously described in detail . Medicat2 and also divided according to the hs-CRP level (<3 mg/l and ≥3 mg/l) based on the clinical cut-off point of 3 mg/l. Patient characteristics are listed in Table Patients were divided according to eGFR ≤ 60 or ≥ 60 ml/min per 1.73 m2, using the CKD classification as proposed by the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines [Four eGFR categories were defined based on eGFR; ≥ 90, 60–89, 30–59, and < 30 ml/min/1.73 midelines . Clinicaidelines .e transformed before analyses to yield a normal distribution. Mean GDS-15 and 4Q scores ± standard error as well as median  were calculated per eGFR and hs-CRP category. The Pearson’s correlation coefficient was used to assess the association between the 12-item GDS depression score (excluding the 3 apathy items) and the 3-item GDS apathy score, as well as the association between the total GDS total score and the 4Q optimism score. The Pearson’s correlation coefficient was calculated between the original optimism score and an optimism score in which all items with a “don’t know” answer were imputed with the mean of the remaining items. A correlation coefficient of 0.95 (P < 0.001) was found in the 463 participants with at least one “don’t know” answer, suggesting that “don’t know” coded as the midpoint was unlikely to have distorted the total optimism score. Analysis of covariance (ANCOVA) was used to determine significance for linear trend over the four categories of eGFR and CRP levels. All adjusted analyses were corrected for the 4 randomized groups  [Because plasma concentrations of hs-CRP showed a positively skewed distribution, levels were logplacebo) .Models were specified for multivariable testing to adjust for possible confounders. Model 1 adjusted for age, sex, level of education, and the 4 randomized treatment groups; model 2 additionally adjusted for BMI, smoking status, alcohol use, antidepressant use, time since myocardial infarction, stroke and diabetes; model 3 was the full model and additionally adjusted for the other possible predictor variables (either creatinine-CysC-based eGFR or hs-CRP level) to determine the independent association of eGFR and hs-CRP with depressive and apathy symptoms, and dispositional optimism. Moreover, we included all three mental well-being parameters (12-item GDS depression score (excluding the 3 apathy items), 3-item GDS apathy score and the 4Q optimism score) into one statistical model as independent variables with eGFR or hs-CRP as the dependent variables. Linear associations were tested using univariate regression analysis. Analyses were stratified for gender, and gender × predictor interaction terms were added to the full model 3 to test whether associations showed a significant difference between women and men.Two additional sensitivity analyses were performed in which, first, we excluded all 221 participants with any missing items on any of the mental well-being questionnaires and, second, we also excluded all 463 participants with a “don’t know” answer on the 4Q as well as the 221 participants with any missing items, leaving 1723 participants available for the analyses.All analyses were conducted using IBM SPSS statistics 20.0 .2. The remaining 605 (26%) patients with an eGFR < 60 ml/min/1.73 m2 were more often female, less physically active, used less alcohol, more often had diabetes, and had a higher mean level of hs-CRP than those with an eGFR ≥ 60 ml/min/1.73 m2. There were 1564 (66%) patients with a low hs-CRP level of ≤ 3 mg/L; the 791 patients with a high hs-CRP level were more often female, more often smoked, and used less alcohol than those with low hs-CRP  had an eGFR ≥ 60 ml/min/1.73 mThe Pearson’s correlation coefficient showed that the association between the apathy score and the 12-item GDS depression score (excluding the 3 apathy items) was only 0.42. The complete 15-item GDS total score and the 4Q optimism score were inversely associated with a correlation coefficient of -0.63.2 had significantly more depressive symptoms (mean GDS-15 score 2.70) than patients with an eGFR ≥ 60 ml/min/1.73 m2 (mean GDS-15 score 1.80). Categories with lower eGFR showed a significant association with more apathy symptoms. Patients with an eGFR ≥ 90 ml/min/1.73 m2 showed significantly less apathy than patients with an eGFR of 60–89 ml/min/1.73 m2. Categories with lower eGFR were also significantly associated with less dispositional optimism  and with less dispositional optimism . All these associations persisted after additional adjustment for hsCRP. Interaction terms showed that relations were similar in women and men . When including all three mental well-being parameters into one statistical model as independent variables with eGFR as the dependent variable, apathy  was the only significant correlate, whereas dispositional optimism (p = 0.12) and the 12-item GDS depression score (p = 0.99) were no longer significant. Moreover, when we excluded the 48 participants with a eGFR < 30 ml/min/1.73 m2 from the analyses, the eGFR was still inversely associated with apathy , independently from CRP and all other covariates.Likewise, linear regression analyses showed that a lower level of eGFR was linearly associated with more depressive symptoms  more apathy symptoms  and less dispositional optimism . However, after additional adjustment for the eGFR, only the association with apathy remained significant . In Fig. p < 0.001) was the only significant correlate, whereas dispositional optimism (p = 0.40) and the 12-item GDS depression score (p = 0.36) were not.In the fully adjusted model, categories of higher hs-CRP serum level showed a significant association with more depressive symptoms, more apathy symptoms and less dispositional optimism Table . Linear p = 0.008), not significant for apathy , and of borderline significance for optimism . In subsequent stratified analyses, associations with depressive symptoms , apathy symptoms  and optimism (β = -0.059 p = 0.014) were stronger in men than in women.When testing for interaction, the interaction term for gender × hs-CRP was significant for depression  showed that the relationship between eGFR and CRP on the one hand, and depressive/apathy symptoms and optimism on the other, were hardly affected. In particular, there was no attenuation as, in the adjusted model, the relationship with CRP increased in strength in the sample of 1723 participants.The present results show that kidney dysfunction (reflected by a lower eGFR) and systemic inflammation (reflected by a higher hs-CRP level) were independently associated with apathy in post-myocardial infarction patients. The associations with depressive symptoms and dispositional optimism were less robust. Kidney dysfunction showed a linear and somewhat stronger association for apathy than for systemic inflammation, for which there seemed to be a threshold value of 7 mg/L.2 had more depressive symptoms than patients with an eGFR ≥ 90 ml/min/1.73 m2 [2 compared to those with a better eGFR. Low apathy was found within the normal range of kidney function. On the other hand, our results are in contrast to those of the only other large study on CHD patients (n = 967) that did not find more depressive symptoms in patients with an eGFR < 60 ml/min/1.73 m2 compared to those with an eGFR of ≥ 60 ml/min/1.73 m2 [2 which reduced the statistical power, and did not include CysC levels or apathy in their analyses. A study in a general population sample of over 28,000 individuals showed an inverse, linear trend relation between kidney function and depression, which did not persist in the multivariable model [We are not aware of previous studies that assessed the relation between kidney dysfunction and apathy symptoms in a large cohort. Nevertheless, our findings are in line with others reporting that patients with an eGFR < 30 ml/min/1.73 m/1.73 m2 –16. We e/1.73 m2 . Howeverle model ; howeverSeveral mechanisms could be involved in the relation between kidney dysfunction and apathy. For example, the vascular apathy hypothesis is suggested to underlie the relation between vascular disease and apathy symptoms . AtherosEarlier studies in CHD patients found no association between CRP levels and depressive symptoms , 23, 44.As opposed to depressive symptoms, optimism has been associated with better health outcomes  in CHD patients and the general population –51. Both2.Some limitations of the present study need to be addressed. First, because psychological measures were assessed at 40 months only, we were unable to address potential temporal relations. Second, because our cohort consisted of post-myocardial infarction patients, the results cannot be extrapolated to other populations. Third, depressive symptoms were assessed using a questionnaire with 15 relatively crude ‘yes/no’ answer categories. Fourth, because we lacked information on proteinuria or hematuria we could not distinguish between the presence or absence of chronic kidney disease in patients with an eGFR of 60–89 ml/min/1.73 mHowever, our study also has several strengths. The study had a large enough sample size to detect small but significant effects. Moreover, we used the combined creatinine-CysC-based CKD-EPI equation to estimate the eGFR, which is considered more accurate than creatinine-based eGFR . Also, u2).In conclusion, the present study shows a significant independent association between kidney dysfunction and apathy in post-myocardial infarction patients. This association was already apparent within the mild kidney dysfunction range. This implies that, at the population level, the impact of kidney dysfunction on mental well-being may be large, since we found that 26% of post-myocardial patients suffer from kidney dysfunction (eGFR <60 ml/min/1.73 m


Rhinitis and asthma share similar immunopathological features. Rhinomanometry is an important test used to assess nasal function and spirometry is an important tool used in asthmatic children. The degree to which the readouts of these tests are correlated has yet to be established. We sought to clarify the relationship between rhinomanometry measurements, fractional exhaled nitric oxide (FeNO), and spirometric measurements in asthmatic children.Patients’ inclusion criteria: age between 5 and 18 years, history of asthma with nasal symptoms, and no anatomical deformities. All participants underwent rhinomanometric evaluations and pulmonary function and FeNO tests.Total 84 children were enrolled. By rhinomanometry, the degree of nasal obstruction was characterized as follows: (1) no obstruction in 33 children, (2) slight obstruction in 29 children, and (3) moderate obstruction in 22 children. FeNO was significantly lower in patients without obstruction than those with slight or moderate obstruction. Dividing patients according to ATS Clinical Practice Guidelines regarding FeNO, patients < 12 years with FeNO > 20 ppb had a lower total nasal airflow rate than those with FeNO < 20 ppb. Patients ≥ 12 years with FeNO > 25 ppb had a lower total nasal airflow rate than those with FeNO < 25 ppb.Higher FeNO was associated with a lower nasal airflow and higher nasal resistance. This supports a relationship between upper and lower airway inflammation, as assessed by rhinomanometry and FeNO. The results suggest that rhinomanometry may be integrated as part of the functional assessment of asthma. Epidemiological and clinical studies suggest a relationship between rhinitis and asthma, because both conditions have a similar pathogenesis and basic immunology , 2. One Rhinomanometry is a simple and useful test that objectively evaluates nasal airway patency , 6, invoFeNO is a small molecule produced by human secretory cells, and is now generally recognized as a marker of airway inflammation . FeNO maThe most likely connection between allergic rhinitis and asthma is that they have the same underlying immunopathology, probably through a type I IgE hypersensitivity reaction with a unified systemic immunological reaction to allergens. The pathophysiological relationship between the upper and lower airways is now well established in adults . HoweverHere we investigated the relationship between rhinomanometry measurements, including nasal resistance and nasal airflow, FeNO, spirometric measurement, and IgE levels in asthmatic children. Besides, plasma IgE and allergic rhinitis symptom scores were also evaluated.Subjects were selected from visitors to the pediatric cardiopulmonary clinic of Kaohsiung Medical University from January 2014 to August 2015 for evaluation of asthma. Patients who met the following criteria were eligible for inclusion: age between 5 and 18 years, and previously or newly diagnosed with asthma, without receiving any inhaled or systemic corticosteroid, nasal or oral antihistamine, or decongestant in recent one week. Asthma was defined according to the Global Initiative for Asthma (GINA) . Those wThe protocol for this study was approved by the institutional review board of Kaohsiung Medical University (KMUH-IRB20140104). Written informed consent was obtained from the parents of all children.3/s), slight obstruction (500-800 cm3/s), moderate obstruction (300–500 cm3/sec), severe obstruction (100–300 cm3/s), and airway closed (< 100 cm3/s) [Nasal flow and resistance in all patients were evaluated using anterior rhinomanometry . Each patient was allowed to rest for 20 min at room temperature 25°C) before being requested to maintain an upright sitting position. After placing a nasal probe into either nostril, the participant was asked to breathe through one nostril with a closed mouth, during which transnasal flow and pressure measurements were recorded using a computer. The average of three consecutive nasal cavity flow measurements was recorded as the final result. All measurements were made using a steady pressure of 150 Pa, as recommended by the European Rhinomanometry Standardization Committee . Ranges °C before0 cm3/s) .FeNO was measured using a Nano Coulomb nitric oxide analyzer  following its instructions and American Thoracic Society (ATS) recommendations; results are expressed in parts per billion (ppb) , 28. BriSiemens Healthineers, USA).Blood samples were collected in a heparin-containing venipuncture tube. Total plasma IgE was measured using a microparticle enzyme immunoassay , mid-flow rate/forced expiratory flow at 25–75% of FVC (FEF25-75), peak expiratory flow (PEF), and FEV1/FVC. Results are expressed as percentages of predicted values.Spirometric evaluations were performed in all participants using a body plethysmograph  at room temperature with patients in an upright sitting position using a nose clip. The best values of at least three consecutive measurements were recorded for each participant. Recorded measurements included forced vital capacity (FVC), forced expiratory volume in 1 s  standard written questionnaire . Writtent-tests. Correlations between variables were evaluated by Pearson’s coefficient. A p value < 0.05 was considered to indicate statistical significance.Statistical analyses were performed using SPSS software . Spirometric and rhinomanometric data are presented as means and standard deviations for all groups. Data were compared between groups using two-tailed unpaired We enrolled 84 patients during the study period. Demographic, FeNO, rhinomanometric and spirometric measurements, and serum total IgE level are shown in 3/s in 33 (39.3%) children, slight obstruction with nasal flow of 500-800 cm3/s in 29 (34.5%) children, and moderate obstruction with nasal flow 300-500 cm3/s in 22 (26.2%) children. No patients had severe nasal obstruction or an airway closed. There were no significant differences between the groups in terms of age (p = 0.533), gender distribution (p = 0.382), body mass index (BMI) (p = 0.532), or BSA  and age ≥ 12 years (26.2%). BMI and BSA in patients aged < 12 years with moderate nasal obstruction were significantly lower than in those with no nasal obstruction or slight nasal obstruction , and FeNO in patients with slight or moderate nasal obstruction was significantly higher than in those with no nasal obstruction  and higher nasal resistance at a given pressure of 150 Pa (p < 0.001) than FeNO < 20 ppb in patients younger than 12 years old . MoreoveThe allergic rhinitis symptoms questionnaire revealed significant differences in total nasal flow, plasma IgE level, and total symptom score (TSS) in subjects whose parents had a history of allergy , but IgE was significantly correlated in a linear fashion with TSS . There was no significant correlation between TSS and total nasal flow  or nasal resistance .Asthma and allergic rhinitis share numerous common pathophysiological features and primary immune responses to a local allergic stimulus, followed by a generalized airway reaction –32. Prev1 or FVC, but did correlate with MEF25 and PEF [Regarding the relationship between FeNO and spirometry, Stănciulescu et al. performed a study in 89 children and found that FeNO did not correlate with FEV and PEF . In the  and PEF . We foun and PEF . Further3/s [In adults, normal nasal resistance under congested nasal mucosal conditions is 0.25 Pa/cm3/s . However3/s . Nasal r3/s . The mea3/s . Other r3/s , 40. We There was no significant correlation between total nasal flow and total IgE in our patients. Total IgE levels are extremely variable and not always associated with asthma severity or airflow limitation . In termA major limitation of our study is the number of cases, which was simply too small to determine the full spectrum of relationships among these parameters. Larger numbers of cases in prospective, randomized studies are needed to determine relationships between rhinomanometric and spirometric measurements, IgE, allergic rhinitis symptom scores, and FeNO. However, the present study provides preliminary results regarding the relationship between the upper and lower airways. As abnormalities in nasal patency are often associated with respiratory symptoms in pediatric patients, information on the degree of nasal patency is thus helpful in selecting decongestive, anti-allergic, anti-infectious, anti-inflammatory, and other therapies, and may help in the management of asthmatic children.In conclusion, our study revealed a significant correlation between nasal airflow as measured by rhinomanometry and FeNO in asthmatic children. In addition to spirometry and FeNO, we thus consider rhinomanometry to be valuable and recommend that it be integrated as part of the functional assessment of asthma.


High-altitude exposure causes a mild to moderate rise in systolic and diastolic blood pressure. This case report describes the first documented case of a hypertensive crisis at altitude, as well as the first report of the occurrence of acute kidney injury in the context of altitude-related hypertension.A healthy, previously normotensive 30-year old, embarked on a trek to Everest Base Camp (5300 m). During his 11-day ascent the subject developed increasingly worsening hypertension. In the absence of symptoms, the individual initially elected to remain at altitude as had previously been the plan. However, an increase in the severity of his hypertension to a peak of 223/119 mmHg resulted in a decision to descend. On descent he was found to have an acute kidney injury that subsequently resolved spontaneously. His blood pressure reverted to normal at sea level and subsequent investigations including a transthoracic echocardiogram, cardiac magnetic resonance imaging, renal ultrasound, and urinary catecholamines were normal.This report challenges the view that transient rises in blood pressure at altitude are without immediate risk. We review the evidence that altitude induces hypertension and discuss the implications for the management of hypertension at altitude. Hypertension is defined as a blood pressure (BP) above 140/90 mmHg , 3. The A 30-year-old Caucasian male, normally resident at sea level with no previous medical history, embarked on a trek to Everest Base Camp (EBC) (5300 m) as an investigator on the Xtreme Everest 2 research expedition . His bloDuring his ascent to EBC, the subject reported minimal symptoms of acute mountain sickness (AMS) that did not require treatment, and was otherwise well. The subject was reviewed by the expedition medical officer on arrival at EBC because his hypertension was persistent. To confirm the accuracy of the blood pressure readings taken with the automated oscillometric blood pressure monitor, measurements were made with another electronic device  and using a manual sphygmomanometer. Since the three methods produced consistent results (observed to be within 5 mmHg of each other on repeated recordings), the Omron was subsequently used for all measurements. The subject remained asymptomatic and physical examination, electrocardiogram (ECG) and urine analysis were normal. Unfortunately due to equipment failure we were unable to examine the subject for signs of retinal haemorrhage or papilloedema. In the absence of symptoms, and after discussion with the expedition medical team and a review of the literature, he initially decided to remain at altitude with twice-daily blood pressure monitoring in the expectation that the increase in BP would be transient as has previously been reported .After 5 days at EBC, the subject’s diastolic BP increased above 110 mmHg (173/114), and a diagnosis of severe hypertension was made  with a urea of 16.2 mmol/L and a creatinine of 168 μmol/L . FurtherThis is the first report of a hypertensive crisis at altitude and the first report of AKI occurring in the context of hypertension at altitude. The case illustrates an individual who experienced large and persistent increases in both SBP and DBP on exposure to high altitude with subsequent reversion of the values towards normal upon descent to lower altitude. Furthermore, this cautionary case suggests that contrary to current opinion , altitudWhilst the prevalence of hypertension in North American and European adults has been reported as high as 44 % , 14, comThe risks of altitude-induced hypertension are currently unclear. There is no evidence to support an association between increased pressures and hypertensive complications such as hypertensive retinopathy, intracranial bleeding, or myocardial infarction , 22–24 oInconsistencies in the current literature may reflect marked inter-individual variability in the hypertensive response to altitude—a point highlighted recently in the Consensus statement of the Medical Commission of the Union Internationale des Associations d’Alpinisme . FurtherAt sea level, guidelines for the management of severe hypertension suggest starting antihypertensive drug treatment immediately, and same day, after hospital admission if signs of papilloedema and/or retinal haemorrhage (hypertensive retinopathy) are present . At altiIf SBP is greater than 180 mmHg or BDP is greater than 120 mmHg and there is evidence of side effects from these elevated pressures, including vision changes, shortness of breath, chest pain, or altered mental status.SBP is greater than 220 mmHg or DBP is greater than 140 mmHg in the absence of symptoms.Unfortunately, we are unable to accurately predict which individuals will respond in this way to altitude and screening all individuals at altitude would be impractical. However, monitoring blood pressure and possibly medication adjustments should be recommended in some individuals. Certainly any individual with poorly controlled or labile hypertension or who has previously had a marked hypertensive response to altitude should be encouraged to self-monitor during ascent to altitude. Such patients should be given clear advice about adjusting medication doses in the event of a severe persistent hypertensive response. It has previously been suggested that medication adjustments in known hypertensive patients at altitude should be considered in accordance with sea-level practices for patients with hypertensive urgency or emergency at altitude , namely:Given the possibility of end-organ damage that our case illustrates, we suggest that descent should also be considered in these circumstances if there is not an immediate response to increasing antihypertensive medications. Furthermore, in patients who are not known to have hypertension, we would suggest that immediate descent should be recommended in the two scenarios outlined above. Commencing new anti-hypertensives in a remote environment, with no knowledge of underlying renal function nor having the ability to predict or monitor possible renal injury, cannot be recommended.Ultimately, given the increasing popularity of high-altitude travel and the relatively high incidence of hypertension, further research is warranted to evaluate this problem. Studies should focus on identifying risk factors for large increases in blood pressure, and in particular, whether a hypoxic stimulus at sea level predicts the altitude hypertensive response. In addition the persistence of altitude-induced hypertension on return to normoxia should be evaluated, as should implications for future hypertensive risk at sea level. Finally, clinical trials to determine the most appropriate treatment for clinically significant blood pressure elevations in this environment are needed.This case report is the first documented case of a hypertensive crisis at altitude as well as the first report of the occurrence of AKI in the context of altitude-related hypertension. This report challenges the view that transient rises in blood pressure at altitude are without immediate risk. Further studies are needed to identify the prevalence of severe hypertension at altitude, to identify risk factors and to clarify the most appropriate treatment. In the absence of sufficient evidence, we recommend a conservative approach of screening at risk patients, increasing medication in known hypertensives with severe hypertension, and consideration of descent in previously normotensive subjects who develop severe and sustained hypertension.


The hypertriglyceridemic waist (HTW) phenotype is defined as the simultaneouspresence of increased waist circumference (WC) and serum triglycerides (TG)levels and it has been associated with cardiometabolic risk in children andadolescents.The objective was to evaluate the influence of HTW phenotype in the fastingglycemia and blood pressure in children and adolescents over one-yearfollow-up period.It is a cohort study involving 492 children and adolescents from 7 to 15years old, both genders, who were submitted to anthropometric, biochemicaland clinical evaluation at the baseline, and also after 6 and 12 months offollow-up. Generalized Estimating Equation (GEE) models were calculated toevaluate the longitudinal influence of the HTW phenotype in the glycemia andblood pressure over one-year.It was observed a prevalence of 10.6% (n = 52) of HTW phenotype in thestudents. The GEE models identified that students with HTW phenotype had anincrease of 3.87 mg/dl in the fasting glycemia mean (CI: 1.68-6.05) and of3.67mmHg in the systolic blood pressure (SBP) mean (CI: 1.55-6.08) overone-year follow-up, after adjusting for confounding variables.The results of this study suggest that HTW phenotype is a risk factor forlongitudinal changes in glycemia and SBP in children and adolescents overone-year follow-up period. Esmaillzadeh et al.4 verified prevalence of 6.5% for HTWin Iranian adolescents (7.3% in boys and 5.6% in girls). In Brazil, transversalstudies with adolescents from 10 to 19 years old identified HTW prevalencefluctuating from 6.4% to 20.7%.7 However, no longitudinal studiesinvolving children and adolescents were identified in the literature.The prevalence of HTW phenotype has been widely investigated. A meta-analysisperformed by Ren et al. (2016)10. Among thesefactors, there are increased glycemia and systemic hypertension, characterized byincreased and sustained blood pressure, with multifactorial determination8. Therefore, HTW is a simple andreliable indicator to detect these diseases and metabolic risks associated tovisceral obesity9, and may become apractical, feasible, and low-cost approach, especially in Primary Care.Evidences suggest that individuals with HTW phenotype are more likely to developmetabolic syndrome and risk factors for cardiovascular diseasesGiven the above, and considering the absence of cohort studies involving the subject,this study aimed to assess the influence of the hypertriglyceridemic waist phenotypeon the fasting glycemia and blood pressure of students after one-year follow-up.7 For systolicblood pressure (SBP), the sample has power of 95% to detect alteration of 10% inthe average values, considering the mean of 111.1 mmHg ± 12.9 SD; andpower of 94% to detect a change of 10% in the mean of diastolic blood pressure(DBP), considering an average of 70.3 ± 9.3SD.11 Calculations of sample power (1-β) werebased on the significance level of 5% and two tailed-tests, indicating that thissample size is sufficient to carry out unbiased estimates of the parameters ofthe studied population.This is a cohort study including 492 children and adolescents from 7 to 15 yearsold, both male and female, from 10 public, urban and part-time schools. It wasconducted a simple random sampling, selecting students of each school from alist of elementary school children registered with the Municipal EducationDepartment of a municipality of Bahia, Brazil, in 2006. This sample has power of97.6% to detect a 10% change in the mean fasting glycemia of the participants,during a 12 months period, considering the mean of 90.2 mg/dL ±0.3SD.All the measurements were collected in the beginning and after 6 and 12 monthsfollow-up.State of pregnancy, lactation or physical disabilities that preventedanthropometric evaluation were adopted as exclusion criteria. However, theseconditions were not identified among the selected students.12 Theanthropometric state was assessed by Body Mass Index (BMI) by age, using asreference, the recommendations of World Health Organization13 for individuals from 5 to 19years old.In order to measure the weight, it was used a Filizola® portable weighingmachine with capacity for 150kg and 100 g precision, allowing the variation of100g. Height was measured by a stadiometer brand Leicester Height Measure, withthe measure performed in the closest millimeter. Both measures were performed induplicate and the mean of the two measures was adopted as finalmeasure.14The waist circumference (WC) was measured at the midpoint between the iliac crestand the outer face of the last rib. The measures were performed in duplicate andthe average of these two measures was adopted as definitive. The cut off adoptedto classify abdominal fat excess was the 90th percentile of the own sample, asproposed by Freedman et al. (1999).The person responsible for the child/adolescent referred this information. Thedemographic variables included the student gender and age. The socioeconomicstatus included number of rooms in the house and people who lived there, themain source of illumination and the occupation of the head of the family. Thesevariables originated the socioeconomic index. The status of household watersupply, the source of drinking water and the destination of the garbage andwaste were used to compose the environmental index. These variables hadresponses varying from 0 (worst condition) to 4 (best classification). Thus, thesocioeconomic and environmental indexes were ranging from 0 to 16 and werecategorized into terciles. Despite knowing that the maternal education isassociated to socioeconomic conditions, this variable was not included in thesocioeconomic index and it was assessed individually, once this also representsthe cultural and dietary aspects of the society where the individual isinserted.The physical activity level was assessed by a questionnaire structured withquestions referring to the frequency of physical activities that were notincluded in the pedagogical content of the school, which is performed once aweek. Therefore, the practice of two or more days of physical activity outsidethe school classifies the student as active; and less than two days of physicalactivity outside classifies the student as less active / sedentary.th Brazilian Guidelines on Hypertension. The BP value wasclassified according to the National High Blood Pressure EducationProgram Working Group on High Blood Pressure in Children(2004),15 consideringhigh pressure levels for children and adolescents BP > p90, according to age,gender and height percentile.For blood pressure (BP) measurement it was adopted the technique recommended bythe 4®), without anticoagulant.The blood was centrifuged at 3000 rpm for 5 minutes for posterior serumseparation, which was used for biochemical determinations. The biochemicalparameters were performed at the Reference City Laboratory, provided by theHealth Department. The triglyceride and glycemia values were determined by theenzymatic method. For the glycemia classification, the recommendation of theBrazilian Diabetes Society (2009)16 was adopted, which characterizes the adequate conditions(≤ 100mg/dL) and increased conditions (>100 mg/dL). Triglyceridevalues < 100 mg/dL were considered adequate.17The blood collection was performed in the morning observing at least 12-hoursfasting, 10 mL of blood were collected by venepuncture and deposited in sterileand disposable vacutainer tubes (BD4The HTW phenotype was defined by the presence of increased waist circumference(> 90 percentile by age and sex of the sample itself) and increased serumtriglycerides (> 100 mg/dL), simultaneously.2- square test.The p-value lower than 0.05 was adopted as significant level.Prevalence of categorical data and measure of mean and standard deviation forcontinuous variables were calculated. The comparison of outcome variables andother variables of interest according to exposition variable was performed usingPearson1when close to one.8Distributions of the mean values of glycemia, the systolic and the diastolic BPaccording to HTW phenotype at baseline and after the follow-up were calculatedusing the statistical test of mean comparison for continuous variables , adopting the p-value lower than 0.05 assignificant level.18The mean and standard deviation of the glycemia, the systolic and the diastolicBP were calculated. The Shapiro-Wilk normality test was applied, and thestatistic indicates normality19Aiming to assess the influence of the HTW phenotype on fasting glycemia and BP ofthe students during 12 months, models of Generalized Estimating Equations (GEE)were built, which is adequate for continuous answers and repeated measures,reflecting the relationship between the variable and independent responses,considering the correlation between the measures in each moment of time.Furthermore, GEE model does not require normality assumption. For the presentstudy, the correlation matrix chosen was the autoregressive, considering thatthe measures have an autoregressive relationship in function of time.Initially, the univariate analysis was conducted, aiming to select the variablescandidate to the multivariate model, selecting those with p value lower than20%. These variables were included in the model as covariables. In the finalmodel, the remaining variables were those that presented significance levellower than 5%.c) was used, which is amodification of the Akaike's information criterion (AIC) forGEE analysis. The QIC is calculated from the comparison of the quasi-likelihoodof the independence model with that of the complete model. The lower the QIC,the better the model adjustment.20To assess the data adjust of the model, the criterion of quasi-likelihood underthe corrected independence model , version 12.0.All the statistical analyses were performed in the statistical packageThe protocol of the present study was approved by the Nutrition Ethics Committeeof the School of Nutrition by the number 03/06.The participation of the student in the study depended on a written authorizationof the parents and/or responsible person. After receiving the letter-invitation,knowing the study objectives and agreeing with the insertion of the minor in theinvestigation, the parents and/or responsible person signed the informed consentform (ICF).In Considering the initial sample of this study, the loss of 37 (7.5%) individuals wasregistered after one year of follow-up. The analysis of the sociodemographic andclinical data indicated that there were no significant statistical differences amongthese factors for the students lost and those that continued in the study (data notshown).The outcome variables  presentednormal distribution, according to the Shapiro-Wilk test; being applied at the meancomparison t-test. Thus, the The GEE models, constructed to evaluate the influence of HTW phenotype in theglycemia and blood pressure of the students after one-year follow-up, are presentedin For the SBP, students with HTW phenotype had increase of 2.97 mmHg in the average ofthis measure after one-year follow-up, when compared to individuals without thisphenotype. This raise in the SBP mean increased for 3.67 mmHg in individuals withHTW phenotype after one-year follow-up when adjusting by sociodemographic variables,BMI and physical activity level .The presented models were well adjusted to the data, according to the QICc criterion,considering that there was a reduction of this indicator in the final models whencompared to the crude models .Significant statistical changes were not identified in the DBP mean in children andadolescents with HTW phenotype after the 12-months follow-up.The results of this investigation indicate higher prevalence of HTW phenotype amongstudents with lower socioeconomic status, with altered fasting glycemia and weightexcess, indicating important environmental component in this phenomenon.Furthermore, the presence of HTW phenotype favored the increase of mean values ofglycemia and systolic BP after one year, especially after the adjustment bysociodemographic variables, BMI and physical activity level.21 and in the United Kingdom (varying from 6.3% to8.2%).22 Investigationsinvolving Brazilian adolescents found the occurrence of HTW phenotype from 2.6% to20,7%.6 These differences among prevalence of HTW phenotypecan reflect the lack of world standardization for measuring the waist circumference,and the serum concentrations of triglycerides for the age, moreover the variationsof the cutoff used to classify the HTW phenotype, which is an obstacle to thecomparison of the investigations. Besides, the differences of lifestyle, geneticbackground and ethnicity interfere with the accumulation of abdominal fat and canexplain the divergent results of the HTW phenotype prevalence.24The prevalence of HTW phenotype identified in this study was higher than that foundin children and adolescents in Iran 26 However, different studies did not find therelationship between HTW phenotype and fasting glycemia in children andadolescents21 but it worth noting the transversal design of theseinvestigations.Data from this study indicate that the HTW phenotype increases the fasting glycemiamean after one-year follow-up when compared to the individuals without the HTWphenotype. This is an important clinical situation among the studied population,because the glycemia is related to visceral obesity, favoring the higher risk ofdeveloping others chronic and non-communicable diseases with expression in adultlife.28 which can explain the longitudinal relationship between HTWphenotype and glycemia identified in this study.The increase of HTW phenotype is associated with metabolic modifications. It issuggested that with increased values of the waist circumference, there are greaterconcentrations of free fatty acids, especially in the liver, muscle and pancreas,resulting from lipolysis of triglycerides. The excess of free fatty acids providesnegative feedback of the glycogen synthase, which can induce the peripheralresistance to insulin and glucose intolerance, in both muscle and liver23 SBP greaterthan 90th percentile for the age, gender and height was observed in 8.8% of the boysand in 17.6% of the girls with HTW phenotype, while diastolic blood pressure was4.4% and 9.6%, respectively. Bailey et al.22 observed higher means of DBP in children and adolescentswith HTW phenotype.Even though some evidences identified the association between HTW phenotype and lipidalterations and in the hyperglycemia in children and adolescents, the relationshipof the HTW phenotype and blood pressure levels is still not established for thisage, because of the reduced number of publications that test this association andthe limitations of the transversal study designs. In the study performed byKelishadi et al.20 Thisassociation is usually weakened or becomes statistically insignificant when BMIadjusts are conducted, suggesting that obesity can influence intensely the bloodpressure and the distribution of isolate fat.The prevalence of high BP in people with HTW phenotype is 2 to 3 times greater whencompared to those who do not present this phenotype.Although it is a cohort study, it is known that it is not possible to completelyestablish a causal relationship, being necessary to undertake confirmatory studiesabout these relationships identified in the present study. Moreover, maybe thefollow-up period was not enough to identify the outcome variables in thispopulation. However, the study was methodologically well designed, robuststatistical techniques were adopted, and, in addition, the results are biologicallyplausible and consistent with the scientific evidence on this theme.29 since theinsulin hormone induces various signals that promote increase of BP, which includesinduction of vasoconstriction and proliferation of smooth muscle cells in bloodvessels; promotion of pro-inflammatory activity; stimulus of renal absorption ofsodium and sympathetic response.32Therefore, in the present study, the longitudinal relationship between HTW phenotypeand SBP was stronger after one-year follow-up, even when adjusted by BMI. This canbe the reflection of the strength of a cohort study and it suggests that thepresence of the phenotype is characterized as risk factor for progressive increaseof SBP in this group. This relationship can be related to the presence of higherserum level of insulin in people with abdominal obesity, regardlessly the bodyweight,The results of this study suggest that HTW phenotype is a risk factor forlongitudinal changes in glycemia and SBP in children and adolescents. Consideringthat the components of this phenotype are already present early in life, themonitoring of HTW phenotype should be adopted in the pediatric group, since it is asimple and low-cost screening tool to identify cardiometabolic risk, and thediagnosis of the risk provided prematurely can favor the nutritional and lifestyleinterventions, promoting health and preventing chronic non-communicable diseases inthe later age.


The contribution of diastolic blood pressure measurement to the diagnosis of classical orthostatic hypotension is not known. We aimed to explore the prevalence of isolated systolic and diastolic orthostatic hypotension components in patients with syncope and orthostatic intolerance.A total of 1520 patients aged >15 years with suspected syncope and/or symptoms of orthostatic intolerance were investigated in a tertiary center using tilt-table testing and continuous non-invasive blood pressure monitoring. Classical orthostatic hypotension was defined as a decline in systolic blood pressure ≥20 mmHg and/or diastolic blood pressure ≥10 mmHg at 3 min of tilt test. The prevalence of upright systolic blood pressure <90 mmHg and its overlap with isolated diastolic orthostatic hypotension was also assessed.One hundred eighty-six patients (12.2%) met current diagnostic criteria for classical orthostatic hypotension. Of these, 176 patients (94.6%) met the systolic criterion and 102 patients (54.8%) met the diastolic criterion. Ninety-two patients (49.5%) met both systolic and diastolic criteria, whereas ten patients (5.4%) met the diastolic criterion alone. Of these, three had systolic blood pressure <90 mmHg during tilt test and were diagnosed with orthostatic hypotension on the grounds of low standing blood pressure. Based on patient history and ancillary test results, causes of orthostatic intolerance and syncope other than orthostatic hypotension were present in the remaining seven patients.An abnormal orthostatic fall in diastolic blood pressure without an abnormal fall in systolic blood pressure is rare among patients with syncope and orthostatic intolerance. Approximately 95% of patients with classical orthostatic hypotension can be identified by systolic criterion alone. Classical orthostatic hypotension (OH) is defined as a sustained reduction of systolic blood pressure (SBP) of at least 20 mmHg and/or diastolic BP (DBP) of 10 mmHg within 3 min of standing or head-up tilt to at least 60°. These expert-based criteria were originally defined in 1996 in a consensus statement endorsed by the American Autonomic Society and the American Academy of Neurology , and werWe aimed to examine the contribution of the SBP and DBP criteria, applied separately and in combination, to the detection of OH. We hypothesized that only a minority of OH patients would be identified by DBP criteria alone. Accordingly, we assessed proportions of patients who met the systolic and diastolic OH criteria from a large database of patients investigated for unexplained syncope and/or orthostatic intolerance.Between September 2008 and May 2016, a total of 1533 patients aged >15 years with suspected syncope and/or symptoms of orthostatic intolerance unexplained by initial evaluation  were invThe patients were asked to take their regular medication and fast for 2 h before the test, but they were allowed to drink water at will. Prior to examination, the patients were asked to complete a questionnaire which explored past medical history, duration, frequency and features of syncope-related symptoms, smoking status and current pharmacological treatment. After supine rest for at least 10 min, a standardized 70° head-up tilt test (HUT) was performed until syncope/presyncope or pronounced symptoms of orthostatic intolerance occurred, or for a maximum of 20 min, followed by optional nitroglycerin provocation according to the Italian protocol . Prior tBlood pressure and heart rate (HR) in the supine position 1 min prior to HUT and at 3 min of HUT were calculated as an average of a 30-s period and recorded in the database. The predefined point for the second hemodynamic assessment at 3 min of HUT was selected to comply with the current definition of classical orthostatic hypotension . If the p < 0.05 was considered statistically significant.The main characteristics of the study population are presented as mean and standard deviation for continuous variables and as percentages for categorical variables. Group differences in continuous variables were compared using analysis of variance (ANOVA), and dichotomous variables were compared using Pearson’s chi-square test. All analyses were performed using IBM SPSS Statistics version 23 software . All tests were two-sided, if applicable, wherein The characteristics of the study population are presented in Table p ≤ 0.001 for all comparisons). One hundred fifty-nine patients with systolic OH (90.3%) were diagnosed with syncope due to OH by the clinicians performing the tests, whereas in the remaining 17 patients (9.7%), systolic OH was detected but not found to be decisive for the syncope etiology.Patients with systolic OH were older and more likely men, had higher supine SBP and DBP, and a higher proportion of hypertension, antihypertensive treatment, and manifest coronary disease compared with non-OH patients , a total of 49 patients met the current systolic criterion of SBP decline ≥20 mmHg; of these, 34 had SBP decline ≥30 mmHg (p < 0.001 for difference between groups). The proportions of patients classified with abnormal orthostatic BP according to different criteria ranged from 11.4% for modified systolic criteria including higher systolic threshold in more severe hypertension, to 12.4% for systolic OH criterion plus standing SBP <90 mmHg but without isolated diastolic OH , i.e. those with systolic OH who had higher supine SBP demonstrated a more pronounced SBP decline during HUT.Patients with supine SBP ≥160 mmHg demonstrated more pronounced changes in SBP, DBP and heart rate after 3-min HUT compared with supine SBP <160 mmHg Table . HoweverWe report here that an abnormal decrease in diastolic blood pressure without an abnormal decrease in systolic pressure is very rare among patients investigated for suspected syncope and orthostatic intolerance. The overwhelming majority of patients with OH can be identified by a systolic criterion. Moreover, the isolated DBP decrease seems not to be decisive for the final diagnosis of syncope and the management of patients.n = 13) proclaimed that a 20-mmHg systolic and/or a 10-mmHg diastolic decline from lying to standing within 3 min of standing should be the standard. The 1996 criteria were primarily based on a study of 92 male and female normal subjects aged 17–61 years [Current diagnostic criteria of OH include both systolic and diastolic cutoff . These c61 years , 25, as In clinical practice, the diastolic criterion is often ignored. This may have several reasons: First, the absolute magnitude of changes in SBP is larger than that of DBP, and is thus much easier to measure. Second, the accuracy of BP measurements may vary by around 5 mmHg  due to bConsequently, for a clinically relevant diagnosis of OH in symptomatic patients, the systolic criteria seem to be sufficient. They will identify approximately 95% of subjects with OH based on the current consensus and the vast majority of abnormal orthostatic BP responses. Adding the absolute SBP threshold of below 90 mmHg on standing may further expand the systolic OH criteria, with the total number of cases being almost the same as for the combined systolic-diastolic criteria. The value of additional systolic criterion may be justified by the fact that symptomatic patients with hypotension (SBP <90 mmHg) on standing may require clinical intervention, and their identification could be important. This is of relevance in individuals with low SBP where the current OH criteria may miss a clinically significant fall in cerebral perfusion due to a narrow range of BP fall.In addition, for resting SBP above 160 mmHg, a higher diagnostic threshold of SBP decline ≥30 mmHg, as previously proposed, could be considered , 29. In A diastolic BP decline within 3 min of standing equal to or greater than 10 mmHg on at least three separate occasions has been proposed by Streeten as a characteristic and obligatory sign of neurogenic OH—i.e. severe autonomic failure . StreeteFrom a clinical point of view, cerebral hypoperfusion is the most important aspect of OH that must be addressed and, in highly symptomatic patients, treated . It has Even though diastolic decline in BP during orthostasis may be less relevant in the clinical diagnosis of OH, its potential impact on long-term prognosis must be borne in mind. Orthostatic hypotension has been consistently associated with increased mortality and incidence of cardiovascular disease in large population-based prospective studies , 22. AltThe current OH diagnostic criteria are based on expert opinion and tests performed in small groups of patients and healthy individuals. The predominant techniques used at that time were active standing test and intermittent BP measurement using auscultatory or oscillometric methods . The preAn isolated abnormal orthostatic drop in DBP without a significant fall in SBP is rare among patients with unexplained syncope and orthostatic intolerance. Approximately 95% of patients with classical OH can be identified by systolic criteria alone. Our data imply that the systolic criterion might be used instead of current OH definition based on both systolic and diastolic criteria.