Daily aerobic exercise such as healthy walking could have an immediate effect on parameters of arterial stiffness; however, there is little evidence in the diabetic population. Our aim, therefore, is to evaluate the association between healthy walking and acute effects on the parameters of arterial stiffness in subjects with type 2 diabetes.The Effectiveness of a multifactorial intervention in diabetics study (EMID), is a study based on an application for smartphones, healthy walking and a nutritional workshop in patients with type 2 diabetes in primary care, is a randomized controlled trial of two parallel groups. This is a subanalysis of the intervention group to evaluate the response to the healthy walking according to age and sex, in 89 subjects with type 2 diabetes, aged between 40 and 70 years. The intervention was a 4 km of a healthy walking at low-moderate intensity. To value our aim, the main study variables were measured before and after it.p < 0.05 for all). It is observed that males have an OR of 2.981 (IC = 95% 1.095 to 8.119) to achieve a reduction in the CAVI (p < 0.05) and an OR of 2.433 (95%CI: 0.871 to 6.794) in the ankle PP (p > 0.05), compared with females.The study population had an average age of 65.0 years (61.2–68.1). After the healthy walking, there was a decrease in the parameters of arterial stiffness: Cardio ankle vascular index (CAVI) of − 0.2 (95%CI:-0.4 to − 0.1) and pulse pressure (PP) of the lower extremities of − 3.9 mmHg (95%CI: -5.9 to − 2.0). Furthermore, in the lower extremities there was a decrease in systolic blood pressure of − 5.3 mmHg (95% CI: -7.3 mmHg to − 3.3 mmHg), in diastolic blood pressure of − 1.5 mmHg (95% CI: -2.6 mmHg to − 0.4 mmHg) (The findings of this study suggest that daily aerobic exercise at a low to moderate intensity, such as healthy walking, has an immediate beneficial effect on the cardio-ankle vascular index, especially in males.NCT02991079.ClinicalTrials.gov identifier:  Cardiovascular disease is the main determinant of morbidity and mortality in patients with diabetes . The preThe protective effect of physical exercise on the cardiovascular system has been widely investigated, however, the immediate effect of the exercise on arterial stiffness is not known with certainty. In the study conducted by De Van et al. , resistaThe findings on the acute effect of the exercise and its magnitude on BP are contradictory, presumably due to the differences in sex and age in the different studies . Nickel Daily aerobic exercise such as healthy walking could have an immediate effect on parameters of arterial stiffness in the population with cardiovascular risk. However, there is less evidence of the acute effect of the exercise in subjects with diabetes, considering also subgroups of age and sex. Therefore, this study aims to evaluate the association between healthy walking and the acute effect on the parameters of arterial stiffness in patients with type 2 diabetes and to analyse the differences for age and sex.The Effectiveness of a multifactorial intervention in diabetics study (EMID) , is a stThis study analysed 89 patients with type 2 diabetes attending La Alamedilla healthcare center. The inclusion criteria were: patients with type 2 diabetes of both sexes, routinely monitored at the health care center, aged 40–70 years who, after receiving information about the study, agreed to take part and signed the informed consent. The inclusion criteria were: patients with type 2 diabetes of both sexes, routinely monitored in the health care center, from 40 to 70 years of age who, after receiving information about the study, agreed to participate and signed the informed consent. The exclusion criteria were: history of cardiovascular events ; documented musculoskeletal, neurological and/or neuropsychological illness, which prevented carrying out the walk; or any other circumstance that, being properly evaluated by the researchers, could interfere with the proper development of the study.With the 89 subjects included, and considering an alpha risk of 0.05 and a common standard deviation of the CAVI of 1.25, our study would have a contrast power for paired groups of 0.62, to detect a difference as statistically significant between the pre-intervention measure (8.6) and the post-intervention (8.3), of 0.3 units.Due to the nature of the intervention, the participants could not be blinded. However, the researcher who carried out the intervention in the study group was different from the person responsible for assessment and standardized counseling. The person responsible for carrying out the measurements before and after the intervention of all the participants was blinded to the objective of the study, to avoid bias. In addition, the person responsible for statistical analysis remained blinded throughout the study.The intervention involved a healthy walking of 4 km, on level ground, leaving from and returning to the health care center, accompanied at all times by health care nursing. The intervention was always conducted at the same time (5 p.m.). These measurements were carried out, having spent at least 2 h since their last meal. In order to make the walks qualify as aerobic exercise (50–70% maximum heart rate) , particiTo evaluate the acute effects of the healthy walking, the main study variables were measured before and immediately after it.2, where ρ is the blood density, Ps and Pd are SBP and DBP in mmHg, respectively, and the PWV is measured between the aortic valve and the ankle  [These parameters were estimated using the Vasera device VS-1500 (Fukuda Denshi) after entering of the participants’ information. These measurements were carried out, having spent at least 2 h since their last meal, with the patien in supine position after resting for 10 min in a quiet room at a stable temperature. CAVI integrates the cardiovascular elasticity derived from the aorta to the ankle pulse velocity through an oscillometric method. The CAVI values were automatically calculated by estimating the stiffness parameter β in the following equation: β = 2ρ × 1/(Ps–Pd) × ln (Ps/Pd) × PWViffness) . The aveiffness) . The ba-iffness) . The CAViffness) –24. In aGlucoMen LX PLUS (A. Menarini GmbH) [A determination of capillary blood glucose was performed, with at least 2 h having elapsed since eating, using the glucose-meter ni GmbH) .Before performing the intervention, the sociodemographic and lifestyle variables were collected: age, sex, marital status, educational level and toxic habits . On the other hand, data were collected on the consumption of drugs, as well as family and personal history of risk factors: hypertension, defined as the use of antihypetensive drugs and/or systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg, measured under basal conditions and making the average of three records; dyslipidemia, described by the consumption of lipid-lowering drugs, as well as, total cholesterol higher than 239 mg/dl or serum triglycerides higher than 199 mg/dl.2). We obtained the measurement of waist and hip circumference, following the latest recommendations of the SEEDO [These values were measured with the subjects barefoot and wearing light clothing. The weight was measured twice  with a certified electronic balance , after having been adequately calibrated with an accuracy of ±0.1 kg. The height was measured twice  with the subject standing, using a portable system . Body mass index (BMI) was calculated by dividing the weight in kg by the square of the height  . This qu2), age (years), hypertension , dyslipidemia  and baseline CAVI value or baseline ankle pulse pressure value (mmHg). For the two-sided tests, an alpha risk of 0.05 was set as the limit of statistical significance. The data were analysed using the IBM SPSS Statistics for Windows version 23.0 .Statistical normality was checked using the Kolmogorov–Smirnov test. Normally distributed continuous variables were expressed as mean ± standard deviation, while non-normally distributed variables were presented as median and 25–75th percentile. T-Student or U Mann-Whitney tests were accordingly used to test the relationship between quantitative variables with Bonferroni correction. Categorical variables were presented as the frequency distribution and compared using the chi-square or Fisher’s exact test when necessary. Pre and post comparison analyses were carried out, using the Student’s t-test for paired data. A logistic regression analysis was performed considering the CAVI and the ankle pulse pressure as dependent variables  and as independent variables sex , physical activity (METs/min/week), DBP (mmHg), BMI (kg/mTable p = 0.012), although this only reached statistical significance in males − 0.3 (95% CI: -0.5 to − 0.1) (p = 0.012), but not in females − 0.1 (95% CI: -0.5 to 0.2) (p = 0.299). Furthermore, in the lower extremities there was a decrease in SBP of − 5.3 mmHg (95% CI: -7.3 mmHg to − 3.3 mmHg) (p < 0.01), in DBP of − 1.5 mmHg (95% CI: -2.6 mmHg to − 0.4 mmHg) (p = 0.007) and in the pulse pressure (PP) of − 3.9 mmHg (95% CI: -5.9 mmHg to − 2.0 mmHg) (p < 0.01). There was an increase in the HR of 9.2 bpm (95% CI: 7.2 bpm to 11.1 bpm) (p < 0.01) and a decrease in blood glucose of − 37.6 mg/dl (− 43.7 mg/dl to − 31.6 mg/dl) (p < 0.01). Comparing the changes of the different variables between males and females, none of these reached statistical significance.The differences in the parameters before and after performing the healthy walking by sex are shown in Table p = 0.033). On the other hand, as in the classification by sex, in the lower extremities, there was a decrease in SBP and in the PP in both groups, but only there was a decline in DBP of − 2.0 mmHg (95% CI: -3.3 mmHg to − 0.7 mmHg), in the older group. Moreover, there was a decrease in blood glucose in both groups, in the ≤64 years of − 37.9 mg/dl (95% CI: -47.6 mg/dl to − 28.2 mg/dl) and in the ≥65 years of − 37.3 mg/dl (95% CI: -45.3 mg/dl to − 29.4 mg/dl). Comparing the changes of the different variables between elders and minors of 65 years, none of these reached statistical significance.Table p < 0.05) and an OR of 2.433 (95% CI: 0.871 to 6.794) to obtain a decrease in the pulse pressure in the ankles (p > 0.05), after the healthy walking, compared to being female.In the logistic regression analysis Table , it can The main findings of the study were that the healthy walking of low-moderate intensity could have an immediate improvement of parameters of CAVI in patients with type 2 diabetes, especially in males and in people over than 65 years, since this is an inexpensive, simple and everyday exercise.Various studies , 13, 27 The intensity and type of exercise deserve key consideration when investigating the effect of exercise on arterial stiffness. Thus, in the study carried out by Mc Clean et al. , they foIn our study, the logistic regression shows that the only variable that could influence the change on the parameters of arterial stiffness after the healthy walking is sex; it being found that males are more than twice as likely as females to reduce the CAVI, compared to baseline, after the healthy walking. Some in vitro studies have described the action of estrogen on the vessels, in the reduction of smooth muscle proliferation  and in tRegarding the blood pressure, there was a decrease in both SBP and DBP in both lower extremities. These results are consistent with the meta-analysis conducted by Carpio et al. , where aConsidering the possible association, of the healthy walking used in our study, with the immediate beneficial effects on the CAVI, blood glucose and BP in the both lower extremities, this could be an activity to be recommended at primary care consultations, especially in males and in people over than 65 years, since this is an inexpensive, simple and everyday exercise. There was no improvement of BP in the upper extremities, this being because healthy walking exercise the both low extremities more intensely, furthermore, these are subjects with type 2 diabetes, a population more likely to have peripheral artery disease that causes a decrease in BP only in both lower extremities, after the exercise. We therefore believe that more studies are required to establish which exercises can be added to the healthy walking to produce cardiovascular improvement in both the upper and lower limbs.This study has various limitations that need to be considered in the interpretation of our results. Firstly, the patients with diabetes included had multiple pathologies, and may be being treated with various drugs, which could modify the CAVI and BP values. We have tried to control this limitation through the inclusion of the most common drugs in the logistic regression. Secondly, being a pre-post intervention study, we had no control group with which to compare the data. Finally, the small size of the sample can make it difficult to find differences caused by the exercise.The findings of this study suggest that daily aerobic exercise at a low to moderate intensity, such as healthy walking, has an immediate beneficial effect on the Cardio-ankle vascular index, in patients with type 2 diabetes, especially in males.


The study was conducted over two weeks. After two weeks, the patients filled out the Asthma Quality of Life Questionnaire (AQLQ), evaluating the quality of their lives throughout the monitored period. Patients exposed to a higher concentration of PM2.5 had significantly lower AQLQ scores. Every 10 µg/m3 of an increase in the concentration of PM2.5 resulted in a decrease of the AQLQ score by 0.16. All domains of quality of life  assessed in the questionnaire were negatively affected by PM2.5. These findings provide an important argument in favor of educating physicians and patients and raising awareness about the detrimental health effects of air pollution. Improving the quality of life of people with asthma requires an immediate and substantial reduction of air pollution.While the negative influence of environmental pollution on the respiratory system is well established, especially for people with bronchial hyper-reactivity, the impact of particulate matter on quality of life in asthma patients is not well understood. Three hundred adult asthma patients were recruited for a study; for each patient, the daily concentrations of particulate matter of 2.5 µm or less in diameter (PM Bronchial asthma is one of the most frequently occurring chronic diseases . Like ev10) has an impact on the quality of life of patients with bronchial asthma [10. No studies were conducted concerning particulate matter of 2.5 µm or less in diameter (PM2.5).The negative influence of particulate matter (PM) on the respiratory system has been known for a long time, especially in the case of patients with bronchial hyper-reactivity ,7. Howevl asthma , with no2.5 (particles which pass through a size-selective inlet with a 50% efficiency cut-off at 2.5 μm aerodynamic diameter) have been classified by International Organization for Standardization as the “high-risk” respirable fraction [2.5, also known as respirable dust, is an exceptionally harmful fraction because it penetrates the smallest bronchioles and the alveoli. Therefore, it may interfere with gas exchange inside the lungs and trigger or exacerbate respiratory diseases. Moreover, some fraction of inhaled PM2.5 (most likely the fraction of particles under 0.1 micrometer) may be capable to translocate into blood vessels and then spread with the blood to various tissues and organs [PMfraction . PM2.5, d organs .2.5 should not exceed 25 µg/m3. At the same time, while considering PM2.5 as “the most harmful among all atmospheric pollutants”, WHO states there is no safe level, below which we can be sure of the lack of negative effects for human health [According to WHO, the maximum 24 h average concentration of PMn health .2.5 air pollution on the self-assessed quality of life of patients with bronchial asthma.In studies conducted to date, researchers evaluated the impact of air pollutants mainly on the aggravation of symptoms of asthma ,12,13. Hn = 349) who were treated in two allergy treatment clinics in Krakow, Poland were recruited for the study between June 2013 and May 2015. The diagnosis of asthma was confirmed by a physician  according to the current guidelines [Patients with bronchial asthma  the patients’ quality of life was evaluated using the Standardised Asthma Quality of Life Questionnaire (AQLQ) for adults [For each patient, we recorded the daily concentrations of PMr adults ,16,17, wr adults . The patThe patients marked their answers to each question on a seven-degree Likert scale, on which 7 meant “no limitations”, and 1 meant “total limitations” in performing particular activities. The overall score of the AQLQ total was the average of all 32 answers, and the score for a particular domain was the average value for the questions within this domain.For analysis, we used the data from 300 patients aged 20–80 years old : 145 women (48.3%) and 155 men (51.7%). Forty-nine patients  were excluded due to leaving the city throughout observation or not filling out/losing the journal of observations. The study was conducted with the approval of the Committee of Bioethics of the Jagiellonian University (number KBET/167/B/2012).2.5 concentrations were additionally characterized by their quartile distribution. PM2.5 concentration was analyzed both as a continuous variable and as a categorical variable, according to its quartile distribution. Potential confounders of PM2.5 exposure and AQLQ, such as gender, education, active smoking, employment status, and having pets at home, were controlled in analyses. Associations between these nominal variables and PM2.5 categories were verified using a chi-square test or the exact Fisher test when appropriate. Differences in the age of patients exposed to different concentrations of PM2.5 categories (different quartiles) were tested using one-way ANOVA . The nonparametric trend in AQLQ values across PM2.5 categories was checked.Data were presented as means with standard deviations (SD) or the frequency with percentage distribution, respectively to its measurement scale. Two-week mean PM2.5 on the quality of life of asthma patients  was estimated with linear regression models using the two-week mean of PM2.5 concentrations both as a categorical variable  and as a continuous variable with a unit of 10 µg/m3, both adjusted to age (in years), gender, and university education (yes versus no) smoking (yes versus no) and season of measurement . Among the variables considered as potential confounders, only age and university education were significantly associated with AQLQ total and its domains in univariate analysis. Gender, smoking, and season of measurement were a priori added to models.The potential impact of airborne PM2.5 exposure level  was used to assess its impact on poor asthma quality of life using ordered logistic regression models adjusted to age, age2, gender, and university education. The same analyses were conducted for all four AQLQ domains, as four separate tests. The proportional odds assumption was verified using the Brant test. The term age2 was added as age had not complied with the proportional odds assumption. The ordered logistic regression models were not adjusted for smoking as it did not affect the risk of poorer asthma life quality. Besides, only 31 (10%) patients were smokers. These patients were attempting to quit smoking and they reported smoking no more than between one to three cigarettes per day at the time of observation. All tests were two-tailed, and significance was set at p < 0.05. All analyses were performed using STATA/IC 13.1 .The AQLQ total was classified into three categories: good quality of life (score: 6–7), reduced quality of life (score: 4–5), and poor quality of life (score: 1–3), ordered from good as “1” to poor as ”3”. PM2.5 exposure (mean in a two-week period) averaged 45.1 µg/m3  and only 75 (25%) patients were exposed to values lower or equal to 25 µg/m3, the 24 h threshold recommended by WHO. PM2.5 measurements were equally distributed across seasons. There were no statistically significant differences between patients in the number of hours spent outdoors. In general, all declared that they spend 2–3 h a day outdoors, on average.PM2.5 exposure levels (classified by quartiles of PM2.5) did not differ significantly in gender, education level (university versus lower), employment status, or keeping pets at home. Nevertheless, patients exposed to higher levels of PM2.5 were older and the studied subgroups were significantly different according to active smoking prevalence . A reduction of 0.6 in the AQLQ total was observed in those exposed to the higher levels compared to those with PM2.5 exposure ≤25 µg/m3, while the deficit in specific domains was statistically significant in the case of AQLQ symptoms and AQLQ environmental stimuli. When quartiles of PM2.5 exposure were compared, after adjustments for the confounders, the effect of exposure became significant in all domains  multivariable ordinal logistic regression models were applied. It was observed that high levels of PM2.5 exposure were associated with over two-fold higher risk of poorer outcomes in AQLQ total , while the very high and extremely high exposure were associated with over seven-fold higher , compared to the low levels of PM2.5 exposure. Similar results were seen in particular domains. The risk of poorer quality of life in AQLQ symptoms reached values from 2.2 times higher for high levels of PM2.5 to 5.3 for the extremely high levels compared to the low levels. Higher risk of poor outcomes in AQLQ environmental stimuli was 3.2 times higher for high levels of exposure and 6 times higher for very and extremely high exposure compared to the exposure to low levels  after adjustment for age, gender, and university education. Similar results were observed in each domain, where a 10 µg/m3 increase in PM2.5 increased the risk of poorer outcomes in all AQLQ domains, from 21% in AQLQ emotional functioning to 46% in AQLQ activity limitation  assessed in the study were significantly reduced as a result of air pollution.In our study, we compared the quality of life of patients exposed to various concentrations of environmental PM2.5 exposure that is significant, but also the degree of exceeding the WHO guideline value as well—in situations where the WHO guideline value was exceeded multiple times all domains of quality of life show lower scores. The most easily influenced factors of quality of life were symptoms of asthma and environmental stimuli, which decrease with every case of exceeding the WHO guideline value.It seems that in evaluating the quality of life it is not just the fact of exceeding the WHO guideline value of PM2.5 fraction, on different aspects of health has been addressed by many studies. The negative impact of PM2.5 on the respiratory system is very well documented by studies, showing connections between concentrations of PM2.5 and longevity [The influence of particulate pollutants, including the PMongevity ,20, freqongevity ,22, the ongevity ,24,25.2.5 has decreased average longevity by 8.6 months in Estonia [3 of reduction in the concentration of this fraction of particles [2.5 leads to increased mortality due to lung cancer [3 of exposure to PM2.5 after excluding other risk factors [2.5 by 10 µg/m3, and the risk was even higher for patients with chronic lung diseases [3 increase in PM2.5 [2.5 and the incidence of lung cancer [Mathematical models estimated that exposure to PM Estonia , and otharticles . Long-teg cancer ,27 and ag cancer . In the  factors . It has diseases . The resin PM2.5 , and in g cancer .2.5 on the respiratory system is confirmed by a systematic review of epidemiological studies [2.5 by 10 µg/m3 caused a 2.07% increase in the incidence of respiratory diseases and an 8% increase in the hospitalization rate [3 of increase in PM2.5 was described [The negative impact of PM studies . Other aion rate ,33. Amonescribed .2.5 have demonstrated a relationship between the increased concentration of this fraction of particulate matter and the incidence of new cases of bronchial asthma [Air pollution causes oxidative stress, leading to inflammatory responses of respiratory tracts and bronchial hypersensitivity—typical features of asthma . Moreovel asthma , as welll asthma ,24,39,402.5 on the quality of life of asthma patients. On the one hand, it may seem that widely available diagnostic methods are sufficient to evaluate the control of bronchial asthma, even though they do not reflect a complete evaluation of the patient’s health, which is influenced not only by physical problems but also by psychological and social issues. That is why, on the other hand, the evaluation of the quality of life, especially in chronic diseases, seems to be important, though not always appreciated. It should be emphasized that quality of life is a crucial element of the contemporary understanding of health [However, previous studies did not investigate the influences of concentrations of PMf health . Thus, iAnecdotal evidence suggests that medical doctors specializing in asthma and allergy often register a correlation between a patient’s worse state of being and periods of increased air pollution, but it is difficult to determine whether this is a result of publicity by a media awareness of air pollution, or if the patients’ quality of life is actually decreased at that time. In our study, we recruited patients that were under the regular care of an allergy clinic. It was a fairly homogenous group, that is, patients with partially controlled asthma, well educated about asthma  and systematically taking their medication.2.5 recorded for the city, while more precise methods of evaluating PM2.5 exposure are potentially available. For example, patients could carry mobile dust monitors. However, technical and financial limitations related to the equipment and patients’ compliance would make such a study expensive and difficult to conduct, especially on a large group of participants. More sophisticated models could be used to assess personal exposure [Our study had some limitations. We assessed individual exposure based on PMexposure ,43,44. A2.5 concentration. The aggravation of symptoms of asthma is often caused by sudden increases in air pollution. Therefore, the peak measurements seem more relevant for exacerbations of asthma than the 14 days average. However, it is worth emphasizing that the quality of life of patients with bronchial asthma does not solely depend on acute asthma attacks. Since AQLQ contains questions concerning the last 14 days, we used two-week mean values of PM2.5 concentration as an exposure indicator metric. It is also worth noting that since there is no guideline value for a two-week average PM2.5 concentration, we used the WHO guideline value, which is a 24 h average value as a limit value. Future studies should also consider other pollutants, since there is growing evidence suggesting the synergistic effect of multi-pollutant exposures [2.5 concentration strongly predicts indoor concentration [Moreover, in our models, we used two-week mean values of PMxposures ,46. Finantration .2.5 concentration, which is easily accessible for citizens, from air quality monitoring stations may predict the quality of life of asthma patients. Being aware that there is no minimum level of safe exposure to PM2.5, physicians taking care of asthma patients should pay special attention to the course of illness and control of patients with bronchial asthma to air pollution, especially in places where high concentrations of PM2.5 occur during many days over the year.Despite all these limitations, we have been able to show that even relatively simple information about PM2.5 impacts the quality of life among people with exceptional predispositions, such as bronchial asthma patients, which serves as an important argument in favor of educational activities, especially concerning public health, and raising awareness of the importance of the issue of air pollution.Exposure to increased values of PM2.5, and it is a fact that should be remembered both by doctors and patients themselves.The deterioration in the quality of life of patients with asthma control and medication suggests the need for special control throughout the illness during periods of exposure to increased concentrations of PMBesides taking measures for the improvement in the quality of air, it seems equally important to raise awareness about sources of air pollution, factors influencing concentration values, and possible methods of reducing ambient and personal exposure, especially among patients with bronchial hyper-reactivity.2.5 should be a priority for public health experts.The substantial reduction of air pollution should be the first and immediate request. Appropriate actions should be taken by governmental organizations, local authorities, and inhabitants. Education and raising awareness about the health risk of high-level PM


Although various agents are used during anesthesia for surgical resection of pheochromocytoma, application of desflurane has rarely been reported. We report the use of desflurane in a case receiving resection of extra-adrenal pheochromocytoma.A 51-year-old female was transferred to our hospital for sustained hypertension. A diagnosis of extra-adrenal pheochromocytoma was made based on increased plasma catecholamine levels and radiographic findings. Surgical resection was planned after controlling blood pressure. General anesthesia was induced with propofol and fentanyl, followed by maintenance with desflurane 4.3% and remifentanil 0.2–0.4 μg/kg/min. Blood pressure and heart rate were stable during induction, tracheal intubation, and tumor manipulation. Blood pressure abruptly decreased to 62/40 mmHg after removal of the tumor, which was treated with noradrenaline. The surgery was completed uneventfully and the postoperative course was also uneventful.Desflurane was safely used in combination with remifentanil during anesthesia for resection of extra-adrenal pheochromocytoma. Pheochromocytomas are rare, catecholamine-producing, neuroendocrine tumors originating from the adrenal medulla or from chromaffin cells in the sympathetic ganglia. Patients with pheochromocytomas often present with the classic triad of diaphoresis, headache, and palpitations and have hypertension. Surgical resection under general anesthesia is the only curative treatment . Both anDesflurane is characterized by rapid elimination and early recovery from anesthesia . Althoug123iodine-metaiodobenzylguanidine (123I-MIBG) corresponding to that mass, which lead to a diagnosis of extra-adrenal pheochromocytoma. Subsequently, administration of oral doxazosin 4 mg and bisoprolol 5 mg daily was commenced and the patient maintained blood pressure of approximately 150/70 mmHg. Doxazosin and bisoprolol were administered for 8 weeks, until the day of and 2 days before surgery, respectively.We have obtained written informed consent from the patient for publication of this case report. A 51-year-old female weighing 61 kg was transferred to our hospital for sustained hypertension. She had been treated with a calcium channel blocker, an α- and β-adrenergic antagonist, and an angiotensin-converting enzyme inhibitor for 7 weeks. There were no symptoms of diaphoresis, headache, or palpitation. Her past history and family history were unremarkable. Physical examinations revealed no abnormal findings except hypertension (207/120 mmHg). Laboratory data were within normal limits, except increased serum noradrenaline  and adrenaline . Serum dopamine, T3, T4, TSH, ACTH, cortisol, renin, and aldosterone levels were in the normal range. Echocardiography demonstrated mild left ventricular hypertrophy with reasonably well-preserved left ventricular function. Computed tomography revealed a heterogeneous mass measuring 31 × 22 mm in the right retroperitoneal space, adjacent to the inferior vena cava (Fig. A central venous catheter was placed in the right jugular vein on the day before surgery. Crystalloid was infused at 100 mL/h during the 3 h of preoperative fasting period. Premedication was not used. Blood pressure was 160/90 mmHg and heart rate was 60/min on arrival at the operating room Fig. . FentanyBlood pressure and heart rate remained stable throughout the initial period of surgery. The tumor was found to be adherent to the aorta and the inferior vena cava, necessitating manual dissection. Besides bolus administration of fentanyl 100 μg, infusion rate of remifentanil was increased to 0.4 μg/kg/min during direct tumor manipulation and was stopped following ligation of the draining vein. Blood pressure abruptly decreased to 62/40 mmHg immediately after tumor resection. A bolus infusion of noradrenaline 50 μg, followed by continuous infusion at 0.05 μg/kg/min, was started and blood pressure increased to 120/60 mmHg. Infusion rate of noradrenaline was decreased by 0.01 μg/kg/min and completely stopped before the end of surgery. CVP was maintained between 12 and 13 mmHg, and stroke volume variation was 9–11% throughout anesthesia.Sugammadex 200 mg was administered on completion of surgery. Increases of blood pressure and heart rate were suppressed by three doses each of nicardipine 0.5 mg and landiolol 5 mg during emergence from anesthesia. Tracheal tube was removed after recovery of spontaneous respiration ≥ 12 breaths/min. The duration of surgery and anesthesia was 2 h 37 min and 3 h 25 min, respectively. Volume of infusion was 2500 mL, blood loss was 100 mL, and urine output was 200 mL. She was transferred to the high care unit, where postoperative analgesia was provided by intravenous patient-controlled analgesia with fentanyl 25 μg/h and acetaminophen 1000 mg every 8 h. She moved to the ward the next morning. Blood pressure was controlled around 160/90 mmHg with a calcium channel blocker and an angiotensin receptor blocker. She had an uneventful recovery with no abnormal laboratory data and was discharged home 10 days later.123I-MIBG lead to the diagnosis. 123I-MIBG scintigraphy demonstrates high sensitivity and specificity to adrenergic tumors [The overall incidence of pheochromocytomas is 0.8 per 100,000 . Patientc tumors  and has c tumors , our casThe choice of anesthetic agent is generally less important than the depth of anesthesia for inhibiting adrenergic and cardiovascular responses . Both inWe should note an increase of blood pressure and heart rate during emergence from anesthesia Fig. . AlthougEvaluation of intravascular volume is essential during removal of pheochromocytomas. We used stroke volume variation for this purpose. It is calculated by continuous arterial pulse contour analysis during mechanical ventilation and is highly sensitive in estimating cardiac preload compared with CVP measurement . DespitePheochromocytomas account for 0.3–0.6% of cases of hypertension , 23. Des


The forced oscillation technique (FOT) measures respiratory impedance during normal tidal breathing and requires minimal patient cooperation.To compare IOS and AOS devices in patients with asthma and COPD.We compared two different FOT devices, namely impulse oscillometry using a loudspeaker (IOS: Jaeger Masterscreen) and airwave oscillometry using a vibrating mesh (AOS: Thorasys Tremoflo) for pre- and post-bronchodilator measurements in 84 patients with asthma and COPD.The overall pattern of measurement bias was for higher resistance with IOS and higher reactance with AOS, this being the case in asthma and COPD separately. There were small but significantly higher values using IOS for resistance at 5 Hz (R5) and 20(19) Hz (R20(19)). In converse, values for reactance at 5 Hz (X5), reactance area (AX) and resonant frequency (Fres) were significantly higher using AOS but to a much larger extent. The difference in AX between devices was more pronounced in COPD than in asthma. Salbutamol reversibility as % change was greater in asthma than COPD patients with AX but not FEV1.Our study showed evidence of better agreement for resistance than reactance when comparing IOS and AOS, perhaps inferring that AOS may be more sensitive at measuring reactance in patients with airflow obstruction.The online version of this article (10.1007/s00408-019-00247-y) contains supplementary material, which is available to authorised users. Current guidelines for asthma and COPD advocate the use of spirometry to quantify the degree of airflow obstruction , 2. SpirOne such method is the so-called forced oscillation technique (FOT) which was originally described by Dubois  using a The application of IOS to asthma and COPD has been previously described in detail elsewhere , 7. In bThe reactance component reflects the balance of inertial and elastic properties of the distensible lung tissue and airways. This is normally measured at a low frequency of 5 Hz (X5) which is denoted as a negative value, along with the area under the reactance curve (AX) between 5 Hz and the resonant frequency (Fres) where the reactance curve crosses the zero line. AX essentially represents where elastance surpasses inertance at lower frequencies, with higher values (denoted as positive numbers) reflecting reduced lung compliance and hence stiffer lungs. Pointedly AX has been shown to be related to exacerbations of COPD as well as to asthma control –13. In aThe primary objective of the present study was to compare head to head the IOS and AOS devices in patients with asthma and COPD.Retrospectively we evaluated IOS and AOS readings of a cohort of 84 adult patients who voluntarily attended our centre for potential screening into clinical trials. Patients included into this study had established diagnosis of either asthma or COPD and were all on prescribed inhaler therapy at the time of visit. During the visit, spirometry, IOS and AOS were performed and asthma patients were asked to complete the six point Asthma Control Questionnaire (ACQ) , 19. SpiFor both IOS and AOS, participants were seated wearing a nose clip, with both hands supporting their cheeks with normal tidal breathing. IOS, AOS and spirometry were measured before and after bronchodilator as inhaled salbutamol 400 µg.n = 58 subjects, after a subsequent software update, we were able to also ascertain R20 for AOS and hence directly compare with R20 for IOS.Following 40 s of tidal breathing for IOS and 20 s for AOS, measurements of R5, R20 (R19 for AOS), Fres, AX and X5 were generated. Each test was inspected for artefacts and a minimum of three measurements were obtained. Readings with coherence values of ≥ 0.7 at 5 Hz were considered acceptable and a between test coefficient of variation of Zrs < 15%. In cases where Fres > 35 Hz, we considered that the associated AX values could not be properly calculated and hence such measurements were excluded from the dataset, although those for X5 remained valid. As the default setting for the Tremoflo device measures resistance at 19 Hz (R19), we compared R20 for IOS versus R19 for AOS in all subjects, and in a subgroup of t tests. Linear regression models were also separately applied to IOS and AOS measurements to assess the model fit. In addition, linear regression was applied to examine the relationship between AX versus FEV1% predicted and versus ACQ, the latter only in asthma patients. p Values are quoted as < 0.05, < 0.01, < 0.001.The data were initially inspected for normal distribution. Bland–Altman analysis was applied to identify the comparative bias between the measurements of two devices. The Bland–Altman data for differences were then analysed with linear regression models to evaluate the degree of bias between IOS and AOS measurements. Comparisons of mean differences between devices were performed using pairwise Student’s 1 (p < 0.001), FEF25-75 (p < 0.001), FEV1/FVC ratio (p < 0.001); higher R5–R20(19) (p < 0.05), AX (p < 0.001) and Fres (p < 0.05); lower X5 (p < 0.05) values compared to those with asthma. Patients with COPD were heavier smokers, while asthma patients were more atopic. Mean coherence values for impedance at 5 Hz and 20 Hz were 0.80 and 0.94 respectively for IOS and 0.89 and 0.95 for AOS.Demographic data on the combined and separate asthma and COPD groups are shown in Table R2 = 0.06, p < 0.05) and for R20(19) . The degree of comparative bias between devices was small showing relatively higher values with IOS, and such differences were significant for post-bronchodilator R5, R20(19) and R5–R20(19) .Bland–Altman plots for resistance revealed good agreement between IOS and AOS with R5 and R20 Fig. . RegressR2 = 0.66, p < 0.001), X5  and Fres . The degree of comparative bias between devices was large showing relatively higher values with AOS for AX and Fres and lower values for X5, with highly significant differences in both pre- and post-bronchodilator values , R20(19) (p < 0.05) for IOS, along with higher AX (p < 0.05), and lower X5 (p < 0.01) for AOS  and COPD (8.40%), while for AX the degree of reversibility was more pronounced in asthma than COPD with AOS: 40% versus 24% (p < 0.05) and IOS: 32% versus 19% (p > 0.05).The % reversibility was similar for FEV1% predicted in the overall population showed a highly significant model fit of moderate effect size for both devices . However, post-bronchodilator AX exhibited a weaker model fit in relation to ACQ for either IOS  or AOS . ROC analysis for post-bronchodilator R5 showed a significant AUC for IOS but not AOS in relation to ACQ value of 0.75: AUC = 0.75 , p < 0.01, sensitivity = 0.79, specificity = 0.6, for a R5 cut point of 0.36 kPa/l.s. ROC analysis for post-bronchodilator AX showed a significant AUC for IOS but not AOS in relation to ACQ value of 1.0: AUC = 0.66 , p < 0.05, sensitivity = 0.62, specificity = 0.62, for a AX cut point of 0.52 kPa/l.Regression analysis for post-bronchodilator AX and X5 in relation to FEVThe main findings of the present study were a small degree of comparative bias between devices for resistance as R5 and R20(19) with relatively higher values being reported with IOS. Conversely, respective values for reactance (as X5 and AX) and Fres were relatively higher with AOS but to a much larger extent. For the combined population of asthma and COPD patients, there was good agreement from the Bland–Altman analysis between IOS and AOS for resistance measured at 5 Hz and 20(19)Hz with a small but significant bias in terms of higher post-bronchodilator values with IOS versus AOS at both frequencies. The mean differences in R5 and R5–R20(19) prior to salbutamol were not however statistically significant, presumably reflecting the wider variance associated with larger pre-bronchodilator resistance values.In the combined population for reactance, there was a much higher degree of comparative bias between devices for AX and X5 values pre and post salbutamol, which was also mirrored by the difference in Fres. This was clearly evident from regression analysis of the Bland–Altman plots where there was a highly significant model fit for the differences. On inspection, the divergence in values between devices became more apparent at higher values of AX above 2 kPa/l. To put this degree of bias in context, the overall mean difference in pre-bronchodilator AX was 1.04 kPa/l amounting to a 73% higher value for AOS than IOS, while for post-bronchodilator AX the difference was 0.64 kPa/l, representing a 65% respective higher value. We believe the magnitude of such difference in AX is likely to be clinically relevant, although we duly acknowledge the lack of any defined minimal clinically important difference values.The higher AX values seen with AOS than IOS at first glance might infer that AOS is more sensitive at detecting changes in low frequency reactance, in turn suggesting that the IOS is perhaps under reading compared to AOS. We believe that this is more likely to be the case than over reading with AOS per se. One possible explanation for the reactance bias is that the pulsed waveforms with IOS are based around a fundamental frequency of 5 Hz, with lower amplitudes occurring at higher frequencies. In contrast, AOS exhibits equivalent amplitudes across a range of non-harmonic prime frequencies and may therefore be less susceptible to distortion. Differences in factory calibration settings and breathing patterns might in part explain the small bias observed in resistance between devices but are unlikely to account for the much larger bias in reactance. One possible solution would be to have defined reference standards for both reactance and resistance in regard to device calibration.One of the strengths of our study was the inclusion of both asthma and COPD patients which resulted in being able to compare the devices over a wide range of reactance and resistance values. On the other hand, a weakness is that we did not have a comparator group of healthy controls. Soares et al.  compared1. The apparent lack of difference in reversibility between asthma and COPD for FEV1 may explained by patients with asthma having a well-preserved pre-bronchodilator FEV1 of 88% predicted, such that there was relatively little room for improvement in response to salbutamol. The greater sensitivity of FOT than spirometry in detecting reversibility is well documented and may be explained by the effect of deep inspiration with spirometry which removes the prevailing vagal bronchomotor tone [A robust aspect of our data was being able to report pre- and post-bronchodilator values when comparing IOS and AOS. As expected we found that the mean differences between devices were smaller for post- compared to pre-bronchodilator values of AX and Fres. In other words, giving a bronchodilator improves the variance between devices. We also found that percentage reversibility response to salbutamol was relatively larger in asthma compared to COPD for AX but not for FEVtor tone . It has tor tone , 23.A potential limitation of our study is that we did not measure serial changes to see if the degree of bias remains constant over time. Without such longitudinal data, we are unable to speculate whether the measurement bias would remain constant over time. We also acknowledge that we did not have any information on exacerbation history in our patients. However, in patients with asthma, ACQ has been shown to being a strong predictor of future exacerbations . MoreoveIn summary, our study showed evidence of better agreement for resistance than reactance when comparing IOS and AOS, perhaps inferring that AOS may be more sensitive at measuring reactance in patients with airflow obstruction.1% predicted showing linear regression line of best fit and 95% CI for IOS and AOS shown separately. The R2 values for the regression model were A) R2=0.51, B) R2=0.35, C) R2=0.53, D) R2=0.36 . The conversion factor from kPa to cmH2O is x 10.2. (EPS 7912 kb)Supplementary material 1 Figure E1 Scatter plot in all patients (i.e. asthma and COPD) of post-bronchodilator AX and X5 vs FEVBelow is the link to the electronic supplementary material.


The aim of this study was to assess the prognostic value of red blood cell distribution width (RDW) in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI).A retrospective cohort study  of 6050 patients who were hospitalized with a diagnosis of coronary artery disease (CAD) and treated with PCI from January 2008 to December 2016 were enrolled in the study. The primary outcome was long-term mortality after PCI. Clinical follow-up data of participating patients were obtained during an outpatient examination 35.9 ± 22.6 months after PCI. Demographic and clinical data and admission laboratory parameters were recorded, and patients were categorized into two groups according to RDW level .P = 0.043). Kaplan–Meier survival analysis suggested that patients with high RDW tended to have an increased accumulated risk of cardiac death. However, we did not found significant differences in the incidence of long-term mortality , MACCE , MACE , stroke, bleeding events or readmission between the two groups.Multivariate Cox regression analysis revealed RDW as an independent prognosis factor for cardiac death. The incidence of cardiac death increased 1.33 times in patients in the high RDW group (HR, 1.331; 95% CI, 1.009–1.755, The baseline level of RDW is an independent predictor for cardiac death in post-PCI CAD patients. Coronary artery disease (CAD) is a complicated multifactor disease. A large number of recent clinical and basic research found that patients with CAD exhibit the traditional risk factors and some newly identified risk factors, such as new lipid parameters, atherogenic index of plasma, nonhigh-density lipoprotein cholesterol and the apolipoprotein B to apolipoprotein A1 ratio . PeripheBiomarkers have become integral to the care of patients with CAD, and sometimes these markers are the key to establishing a diagnosis, determining risk, and guiding therapy. As one of the characteristic parameters of blood, red blood cell distribution width (RDW) was only used for the diagnosis and differential diagnosis of anemia before 2007. Felker et al.  found thThe Clinical Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI (CORFCHD-PCI) study is a large, single-center retrospective cohort study based on case records and a follow-up registry performed in the First Affiliated.http://www.chictr.org.cn (Identifier: ChiCTR-INR-16010153). The CORFCHD-PCI study was designed to evaluate the clinical outcomes and risk factors.Hospital of Xinjiang Medical University. The details of the design are registered at of CAD patients after PCI. We collected demographic data, clinical characteristics, risk factors, blood samples, biochemical data, electrocardiographs (ECG), echocardiography, coronary angiography, PCI procedure, and long-term outcomes for CAD patients who underwent PCI in the First Affiliated Hospital of Xinjiang Medical University from January 2008 to December 2016. The study protocol was approved by the ethics committee of the First Affiliated Hospital of Xinjiang Medical University. Because of the retrospective design of the study, the need to obtain informed consent from eligible patients was waived by the ethics committee. Follow-up data were obtained via review of the medical records and/or telephone interview with the patient or family members.Hypertension was defined as a systolic blood pressure of > 140 mmHg and/or a diastolic blood pressure of > 90 mmHg in at least 2 measurements or the use of any antihypertensive drug. Diabetes mellitus was defined as fasting plasma glucose levels of 126 mg/dl on multiple measurements or current use of anti-diabetic medications. Hypercholesterolemia was considered total serum cholesterol of > 200 mg/dl or the use of lipid-lowering medication. Smoking and drinking status was defined as current tobacco and alcohol use.Peripheral venous blood samples of the patients were obtained on admission in the inpatient ward. Data on clinical and demographic characteristics, including age, sex, history of hypertension and diabetes mellitus, and smoking and drinking status, were collected from medical records. Echocardiography and laboratory data, including complete blood cell count, lipid parameters and left ventricular ejection fraction (LVEF) were noted. During the follow-up period, the use of β-blockers, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), statins, aspirins, clopidgrel and calcium channel blockers (CCBs) were recorded.The primary endpoint of the study was long-term mortality, including all-cause mortality (ACM) and cardiac mortality. The key secondary endpoints were stroke, bleeding events, readmission and major adverse cardiac events (MACE), which were defined as the combination of cardiac death, recurrent myocardial infarction, and target vessel reconstruction as described previously . Briefly2) tests were used to compare categorical variables. Multivariate Cox regression analysis was used for determinations of independent parameters for prognosis. Sequential models were developed to examine the incremental prognostic value of the parameters. Incremental factors added to the model at each step were considered significant when the difference in the log-likelihood associated with each model corresponded to P < 0.05. Long-term survival was analyzed using the Kaplan-Meier method. The P values were 2-sided, and P < 0.05 was considered significant.SPSS 22.0 Statistical Package Program for Windows  was used for all statistical analysis. The study population was divided into two groups based on RDW level. The Kolmogorov-Smirnov test was used to assess normality of distribution. Continuous variables with a normal distribution are reported as the mean ± standard deviation, and categorical variables are specified as numbers and percentages. To compare parametric continuous variables, Student’s t tests were used, and to compare nonparametric continuous variables, Mann-Whitney U tests were used. Chi-squared . We divided RDW into two groups according to the median. Baseline characteristics of the two groups are shown in Table P < 0.05). High proportions of males, high rate of drinking, smoking, and diabetes incidence and higher fasting blood glucose (FBG) were found in the low RDW group (P < 0.05).The follow-up charts of participants are shown in Fig. 1P < 0.001). The incidences of readmission, main adverse cardiovascular and cerebrovascular events (MACCE) MACE, cardiac death and recurrent myocardial infarction were also significantly different between the two groups (P < 0.05), and significant increases were observed in the higher group. Although there was a significant difference in the use rate of aspirin between the two groups, we did not find differences in the incidence of bleeding events or stroke between the two groups  in univariate Cox models were entered into multivariate Cox regression analysis. In multivariate Cox regression analysis, after adjusting for the traditional clinical prognostic factors, including age, sex, diabetes, hypertension, smoking, drinking, SBP, HR, BUN, Cr, FBG, use of statins, aspirin, and clopidgrel, which were the significant factors in univariate Cox models, we found that RDW also predicted poor clinical outcomes. RDW was an independent predictor for cardiac death in the high RDW group. The incidence of cardiac death increased 1.33 times  (Table P = 0.140), MACCE , recurrent myocardial infarction , stroke , bleeding events  or readmission  among two groups (Tables not shown).Univariate models for each of the predictor variables were created, and variables that were significant P < 0.0 in univaKaplan–Meier survival analysis suggested that patients with high RDW exhibited increased accumulated risk of cardiac death Fig. .Fig. 2CuP = 0.03) after a mean period of 1.8 ± 1.3 years. Fatemi et al. [P = 0.001). Several studies also found a high baseline RDW value in patients with specific baseline characteristics, such as non-anemic at baseline, [The present studies investigated the prognostic value of RDW in CAD patients with PCI and found that RDW was an independent poor prognosis factor at levels ≥13.1%. High levels increased long-term cardiac death 1.33 times. To reduce the risk of confounding, we adjusted for a comprehensive list of characteristics that influence the risk of cardiovascular events to examine the association between RDW and clinical outcomes. Uyarel et al.  retrospei et al.  enrolledaseline,  diabeticaseline,  or elderaseline,  undergoiaseline, , 28. OurHigher levels of RDW within the normal range may indicate accelerated red blood cell destruction or, more commonly, ineffective erythropoiesis. The identification of a putative mechanism is hampered by the lack of epidemiological studies demonstrating the factors that are associated with anisocytosis . The exa3 deficiency on bone marrow erythropoiesis. The concurrent red blood cell deformability diminution may result in impaired flow through the microcirculation. It is impossible to unambiguously ascertain which concomitant factors, including lipid, glycemic and iron metabolism disturbances, anemia, vitamin D3 deficiency, oxidative stress, inflammation, and the diminution of erythrocyte membrane deformability, are the primary causes of the poor prognoses observed in patients with CAD.In addition to inflammation, oxidative stress may be another important mechanism to explain the underlying relationship. Oxidative damage is prone to reduce cell survival and have a disadvantage on the homogeneity of erythrocytes. As the primary “oxidative sink”, erythrocytes have tremendous antioxidant capacity, and the variation in erythrocyte size is associated with oxidative stress, likely via increased red blood cell turnover . Bujak eOur study has some limitations that should be considered. First, this study failed to monitor and measure inflammation changes, neurohumoral markers, including C-reactive protein, brain natriuretic peptide and other pro-inflammatory cytokines, angiotensin II and norepinephrine levels, and these indicators may better explain the higher RDW values, which are increased in patients with malignant mechanism, on the risk of cardiac events. Second, the present study was a single retrospective cohort design. Therefore, our results must be further verified in a multicenter, prospective study to confirm the association between RDW and adverse outcomes.In conclusion, our findings are notable because RDW is widely available to clinicians as part of the complete blood count, incurs no additional costs, and may be a novel marker of cardiovascular prognosis.


To evaluate the physical activity level and functional capacity of children and adolescents with congenital heart disease and to describe correlations between functionality, surgical and echocardiographic findings, metabolic and inflammatory profile and differences between acyanotic and cyanotic heart defects. A cross-sectional study including children and adolescents with congenital heart disease between six and 18 years old that were evaluated with the 6-minute walk test (6MWT) to assess functional capacity. The short version form of the International Physical Activity Questionnaire (IPAQ) was performed to evaluate physical activity levels. Also, echocardiography and blood collection, to evaluate the metabolic  and inflammatory markers (C-reactive protein), were assessed. Twenty-five individuals were evaluated. Of them, 14 had acyanotic heart defects and 11 cyanotic heart defects. Mean age was 12.0±3.7 years, and 20 (80%) were male. IPAQ showed that six (24%) individuals were very active, eight (32%) were active, nine (36%) had irregular physical activity, and two (8%) were sedentary. The mean distance walked in the 6MWT, considering all studied individuals, was 464.7±100.4 m, which was 181.4±42.0 m less than the predicted (p=0.005). There was a positive correlation between Z score 6MWT and the number of surgical procedures . Children and adolescents with congenital heart disease have low functional capacity, but they are not completely sedentary. However, there was a consequent increase in long-term morbidity, due to surgical sequelae, inflammatory responses associated with cardiopulmonary bypass,,Physical inactivity is associated with increased risk of coronary heart disease, and healthy physical activity habits are established during childhood. It has been shown that regular, organized and early physical activity in schools leads to tracking of healthy physical activity habits into adulthood.Inflammatory markers and metabolic derangements are changes expected, especially in children and adolescents with excessive weight.,,,,Low levels of physical activity are directly related to functional capacity.Thus, the objective of the present study was to evaluate the physical activity level and the functional capacity of children and adolescents with CHD using the 6MWT. We also investigated the existence of possible correlations of functional capacity with surgical and echocardiographic findings, metabolic and inflammatory profile and differences between patients with acyanotic and cyanotic CHD.This was a cross-sectional study with children and adolescents between 6 and 18 years old, with medical diagnosis of CHD, followed at the Pediatric Cardiology Outpatient Clinic of a referral hospital in south of Brazil between February 2011 and March 2012. The study was approved by the institution’s Research Ethics Committee, and patients or guardians signed a written informed consent form. Exclusion criteria were: lower limb malformations, wheelchair use, and neurological sequels or other medical conditions that would prevent the proposed evaluations.Initially, an evaluation form including data about underlying disease, previous surgeries or the presence of residual lesion was completed. Data were collected using a questionnaire administered by health professionals who attended specific training. Weight was measured to the nearest 0.1 kg, and height to the nearest centimeter, using an electronic digital scale with stadiometer  with 200-kg capacity, with the child standing, without shoes or heavy clothing. Nutritional status was based on body mass index (BMI), and classified using the software WHO Anthro and AnthroPlus .The short version of the International Physical Activity Questionnaire (IPAQ), validated in Brazil, which assesses physical activity level, was applied by a health professional specifically trained for this task. The questions are related to the time spent walking as a means of locomotion, performing vigorous and moderate activity. As a result, patients are classified as very active, active, irregularly active or sedentary.The 6MWT was conducted on a 20-meter corridor marked at each meter. Participants were accompanied by the researchers and stimulated by standardized verbal commands to walk over the longest possible distance within 6 minutes, according to the American Thoracic Society (ATS) guidelines.Blood samples were collected after a 12-hour fast. Laboratory examinations included blood glucose , triglycerides , total cholesterol , high-density lipoprotein (HDL) cholesterol , low-density lipoprotein (LDL) cholesterol , complete blood count , C-reactive protein , and insulin levels .All patients underwent a comprehensive transthoracic echocardiographic study, at rest in the supine position, with conventional methods. The end diastolic and systolic diameters were measured through the internal dimensions of the left ventricular cavity, obtained by two-dimensional and M-mode images from the parasternal window, with longitudinal viewing. The left ventricular ejection fraction was estimated by the Teichholz’s formula,The categorical variables were described as frequencies, and numerical variables as mean and standard deviation  or as median and 25-75 percentiles . A sample size of 25 was estimated based in the difference of 180 m between predicted and walked distance observed by Moalla et al.Independent sample Student’s t-test and Mann-Whitney U test were used to compare means between groups, according to the data distribution. The associations between physical activity levels determined by the IPAQ, distance walked in the 6MWT, echocardiographic findings and metabolic and inflammatory profiles were evaluated with Spearman’s or Pearson correlation coefficients. McNemar’s test was used to compare the perception of dyspnea and fatigue by the Borg scale between the groups (cyanotic versus acyanotic CHD), in which we compared the prevalence of zeros for fatigue and dyspnea at the beginning and at the end of the 6MWT. The analyses were performed using the software Statistical Package for the Social Sciences (SPSS) version 14.0 , and the significance level in all analyses was 5%.The sample was composed of 25 individuals, predominantly male (80%), mean age 12.0±3.7 years. Fourteen individuals had acyanotic CHD and 11 cyanotic CHD. Clinical data, anthropometric variables and levels of physical activity assessed by IPAQ are exposed in The most frequent acyanotic CHD was interventricular and interatrial communication, in three individuals, followed by the atrioventricular septal defect and pulmonary stenosis, in two patients each. Other heart defects in this group, included coarctation of the aorta, bicuspid aortic valve, aneurysm of the sinus of Valsalva and aortic stenosis/regurgitation, affecting one individual each. In the cyanotic CHD group, the most common lesion was tetralogy of Fallot (ToF), affecting seven individuals, followed by truncus arteriosus, double outlet right ventricle, transposition of the great arteries and double inlet left ventricle, affecting one patient each. All seven patients with ToF underwent total surgical correction; one needed a Blalock-Thomas-Taussig shunt before total correction. The patient with transposition of the great arteries underwent arterial switch (Jatene procedure). One of the patients with pulmonary stenosis needed an aortic homograft. The two patients with univentricular heart underwent Glenn procedure followed by Fontan operation.The functional capacity of the patients, evaluated by the distance walked in the 6MWT, is presented in Other results from the 6MWT are presented in No correlation was found between the distance walked in the 6MWT and extracorporeal circulation total time , age of definitive surgery , ejection fraction  and C-reactive protein . The correlation of the 6MWT and echocardiographic, surgical and laboratory data showed that patients who underwent less surgical procedures presented Z scores for 6MWT .This study with CHD patients showed that a low percentage of children and adolescents is sedentary, according to the IPAQ, but their functional capacity is reduced, compared to that predicted. The functional capacity was similar in patients with cyanotic or acyanotic CHD.The mean distance walked in the 6MWT in the present study was 181.4 m shorter than predicted by gender, height, and age, which is in agreement with other studies,Although only 8% of children and adolescents included in this study were sedentary, the frequency of very active individuals was low (24%). In an investigation of the level of physical activity in 153 adolescents with CHD, Lunt et al. observed that approximately 30% reported the recommended level of physical activity.There were no differences between patients with acyanotic CHD and cyanotic CHD, but both groups showed less distance compared to the predicted. Also, correlation was found between the number of surgical procedures and Z score 6MWT.Patients who undergo more surgical procedures are more often restricted in their daily activities and consequently restricted to the exercise, in addition to presenting more serious injuries that require multiple surgical procedures.The higher C-reactive protein levels in acyanotic and cyanotic CHD patients may indicate some degree of residual hypoxemia, which could result in the release of inflammatory mediators, even after surgical correction. Similar results have been shown by Tomita et al. in individuals with CHD and hypoxemia.Another important point to consider is the great variability among the different kinds of congenital heart lesions. In the present study, there were two patients who underwent Fontan operations, and one of them did not complete the test. It is expected that acyanotic and well-corrected acyanotic and biventricular lesions would have a better functional performance. These individuals have the capacity of increasing pulmonary perfusion during exercise, as opposed to Fontan patients, who increase pulmonary ventilation, but not perfusion in the same levels.Considering blood pressure, systolic blood pressure rarely exceeds 200 mmHg in the maximum effort in children and adolescents, and diastolic blood pressure rarely increases significantly, more frequently falling or staying in basal values. In the present study, the systolic blood pressure did not change after the 6MWT, and the diastolic blood pressure increased only in acyanotic CHD patients, which can be explained by the fact that the systolic blood pressure at rest is higher in these patients than in cyanotic CHD individuals.No differences in the degree of dyspnea and fatigue of lower limbs were observed after 6MWT, as assessed by the Borg scale, an instrument that allows a subjective evaluation of the intensity of exercise. Hommerding et al.The main limitation of this study was that CHD is a disease with low prevalence and high heterogeneity regarding exercise restrictions, prognosis and result of surgical/invasive interventions, thus making it difficult to evaluate a group as a whole. Individual characteristics must be accounted for, and larger groups of specific lesions are needed to issue clinical recommendations. Additionally, the instrument used to evaluate the level of physical activity was the IPAQ short version, that measures only physical activity intensity and time. The IPAQ long version evaluate different activities in various areas, such as work, travelling, leisure or domestic activities, and each of these domains is more explored than in the short version.In conclusion, children and adolescents with CHD are rarely completely sedentary, but the frequency of very active patients is low, featuring a population with less healthy lifestyle habits than usual in this age group. The functional capacity, lower than predicted for gender, age and height, is in agreement with this information, and is similar among individuals with cyanotic and acyanotic CHD. These findings are preliminary and should be confirmed in larger samples. Results showing that patients with cyanotic CHD can maintain some degree of inflammation in the long run, even after surgical correction, need to be confirmed in further studies. These results are relevant for the planning of preventive measures in this group of patients, mainly with regard to recommendations for physical activity of patients and guidance for the families according to the specific indications in each case.


Symptoms of orthostatic intolerance (OI) are common in Chronic Fatigue Syndrome (CFS) and similar disorders. These symptoms may relate to individual differences in intracranial compliance and cerebral blood perfusion. The present study used phase-contrast, quantitative flow magnetic resonance imaging (MRI) to determine intracranial compliance based on arterial inflow, venous outflow and cerebrospinal fluid flow along the spinal canal into and out of the cranial cavity. Flow-sensitive Alternating Inversion Recovery (FAIR) Arterial Spin Labelling was used to measure cerebral blood perfusion at rest. Forty patients with CFS and 10 age and gender matched controls were scanned. Severity of symptoms of OI was determined from self-report using the Autonomic Symptom Profile. CFS patients reported significantly higher levels of OI (p < .001). Within the patient group, higher severity of OI symptoms were associated with lower intracranial compliance  and higher resting perfusion . In both groups intracranial compliance was negatively correlated with cerebral perfusion. There were no significant differences between the groups in intracranial compliance or perfusion. In patients with CFS, low intracranial compliance and high resting cerebral perfusion appear to be associated with an increased severity of symptoms of OI. This may signify alterations in the ability of the cerebral vasculature to cope with changes to systemic blood pressure due to orthostatic stress, but this may not be specific to CFS. Orthostatic intolerance (OI) refers to symptoms that occur when individuals assume an upright posture, often from lying down, which are relieved once the individual returns to a supine posture including light-headedness, dizziness, blurred vision, headaches or sweating. They are accompanied by changes in heart rate or blood pressure. In extreme cases OI can lead to a temporary loss of consciousness (syncope). OI is frequently reported in patients with Chronic Fatigue Syndrome (CFS) or Myalgic Encephalomyelitis (ME). There iDue to its high metabolic demand the human brain is particularly vulnerable to blood flow alterations, and various mechanisms act to maintain relatively stable cerebral perfusion despite varying systemic blood pressure . Some ofAlterations in peripheral vascular compliance have previously been reported in CFS , but it CFS is also associated with cerebral hypoperfusion –16, thouThe current study used magnetic resonance imaging (MRI) techniques to measure intracranial compliance and cerebral perfusion in a comparatively large sample of patients with CFS and a sample of age and gender matched control participants. The two groups were compared and the relationship between the MR based measures and OI were examined.A group of 40 patients with CFS  participated in this study as part of a larger project investigating the role of autonomic dysfunctions in CFS. Participants with CFS were recruited via the Newcastle and North Tyneside National Health Service (NHS) Clinical CFS Service. Consecutive patients attending the clinic were provided with a Patient Information Sheet and invited to contact the research team if they were willing to be involved. Participants were not selected positively or negatively according to any criteria other than the fact that they were attending the clinical service and had a Fukuda diagnosis of CFS , althougA control group of 10 volunteers  were recruited and matched to the patient group in terms of age and sex. Control participants were recruited via notices provided in the hospital and University together with a distribution of posters via the local patient support group. Control participants fulfilled the same inclusion and exclusion criteria as CFS participants other than the fact that they did not have a CFS diagnosis. In addition, controls were required to be sedentary defined as on average not performing more than 30 minutes a week of moderate exercise. This was meant to ensure that any potential differences between the groups would not simply be attributable to differences in levels of everyday activity.All participants gave written informed consent to the study. The study was conducted in accordance to the Declaration of Helsinki. The study was reviewed and approved by the Newcastle NHS ethics committee .All participants completed the full Autonomic Symptom Profile (ASP) . The resParticipants were scanned on a 3T Achieva®  MRI scanner with an 8-channel head coil. In addition to standard, clinical T1- and T2-weighted anatomical brain scans, two sets of scans were performed to assess intracranial compliance and perfusion. For intracranial compliance, a set of three cardiac-gated phase contrast scans were performed to quantify the intracranial volume and pressure change profile across to the cardiac cycle. Scans were collected in a single slice  positioned at the base of the skull  to minimize the influence of neck vessel compliance on the measurements , and pla3, 10 axial slices). Sixty tag-control image pairs were acquired with a post inversion delay of 1500ms. Additional inversion recovery scans with inversion times of 900, 1200, 1800, 2100 and 2400ms were acquired for T1 estimation.Cerebral perfusion was assessed using flow-sensitive alternating inversion recovery (FAIR) arterial spin labelling (ASL) scans. ASL scans utilized variable-rate selective inversion pulses  and gradICC calculations were based on the measured velocities in four arteries , the left and right internal jugular vein and the CSF flow along the spinal canal as previously described . For eac-1) of this profile was used to calculate the intracranial compliance index (ICCI), which divided the peak-to-peak volume change by peak-to-peak pressure gradient.Velocity profiles were extracted for each of the selected voxels. These were then used to calculate arterial inflow, venous outflow, CSF flow and the intracranial volume change profile (ΔV(t) in ml), which measures the compression and expansion of intracranial tissue due to the differential inflow and outflow of fluids to and from the cranial cavity. As only a limited number of blood vessels were assessed, this profile was corrected such that cumulative inflows and outflows over the full cardiac cycle were equal. The overall peak-to-peak volume change was used in the compliance calculation. Flow-velocities of the CSF were used to calculate a pressure gradient profile (ΔP(t)/d) as described elsewhere . The peahttp://www.fil.ion.ucl.ac.uk/spm/). The average tag-control signal level difference of the FAIR scans was used to calculate blood perfusion values according to a standard kinetic model [ASL images were re-aligned to the first scan and co-registered to the anatomical scan using rigid-body transformations. All subsequent ASL processing was based on extracted signal levels from the grey matter segment, which was derived from a high-resolution anatomical scan using standard segmentation routines implemented in SPM8 . Group comparisons were performed using parametric tests , with the exception of ASP scores, which utilized a non-parametric rank test. Within groups, Pearson bivariate and partial correlations were calculated to assess relationships among the measures.OI+Syn scores are shown in -1 . In the control group ICCI ranged from 4.08 to 22.31 ml/mmHg*cm-1 . There was no significant difference in ICCI between the two groups, t(49) = 0.339, p = .74. Grey matter CBF  or ICCI .The current study indicates a potential role of ICC in the severity of symptoms of OI in patients with CFS. As expected, almost all CFS patients in our sample reported various levels of OI via self-report that were significantly higher than those reported by the healthy control group. In the patient group there was a negative relationship between OI symptom severity and ICC, as those patients with higher compliance tended to report lower OI symptoms (and vice versa). Furthermore, there was a positive correlation between orthostatic symptoms and cerebral blood perfusion in grey matter. This suggests that CFS patients who report more severe orthostatic symptoms have higher levels of resting cerebral perfusion than those patients who report fewer or only milder orthostatic symptoms.While, as expected, orthostatic symptom severity was significantly higher in the patient group than in healthy controls, ICC did not differ between the two groups. A previous study that used very similar MR methods was also unable to find differences between CFS patients and controls in pulsatile CSF flow parameters . SimilarWhile the relatively small size of our control group may have prevented us from identifying group differences in compliance or perfusion, even the mean values were numerically very close to each other so that a simple lack of statistical power is unlikely be the sole reason for not finding group differences. It should however be noted that our control group was deliberately recruited to be mostly sedentary and therefore may not have been at optimum levels of general health itself. Furthermore, the relationship between ICC and cerebral perfusion appeared to be very similar in both groups. This suggests that ICC and cerebral perfusion were not altered in our CFS patients relative to the control group. Instead it appears that low intracranial compliance, which was strongly negatively coupled to higher resting perfusion, is associated with experiencing higher severity of symptoms of OI in the CFS group if the cardiovascular system is not capable of providing adequate blood supply to the brain due to an orthostatic stressor.The negative relationship between ICC and cerebral perfusion may seem puzzling at first. However, given that the ICCI is inversely proportional to the peak-to-peak pressure gradient, lower compliance may be an expression of larger pressure gradients, which may increase blood perfusion. Indeed, in patients there is a significant positive correlation between CBF and the peak-to-peak pressure gradient, but not with peak-to-peak intracranial volume change. In contrast, CBF in controls showed a significantly negative correlation with intracranial volume change , but no significant correlation with peak-to-peak pressure gradient . In other words, the negative relationship between ICC and cerebral perfusion appears to be primarily determined by pressure differences in patients, whereas it is primarily determined by volume changes in controls.It should also be noted that CBF and compliance measurements were made at rest while participants were in a supine position on the MR scanner bed. A study in healthy volunteers using a low-field, vertical gap MRI scanner and comparing a supine to an upright posture showed that these parameters are indeed posture dependent . It is cHowever, studies using transcranial Doppler ultrasonography showed that patients with POTS and healthy controls have near identical blood flow velocities in the middle cerebral artery, which decreased equally with increasing levels of tilt , 37. InsIn summary, we present evidence for a relationship between the degree of self-reported severity of orthostatic intolerance in patients with chronic fatigue syndrome and MRI based measures of intracranial compliance and cerebral blood perfusion. Patients with more severe OI symptoms exhibited lower levels of ICC and higher levels of cerebral perfusion. While neither of those measures was significantly different from the control group and an inverse relationship between compliance and perfusion was observed in both CFS patients and in controls, reduced ICC may constitute a risk factor for experiencing symptoms of orthostatic intolerance as it might reduce an individual’s ability for effective cerebral autoregulation. Whether the supine posture in the MR scanner had elevated cerebral perfusion in individuals with low compliance remains unclear and should be the subject of further investigation. Future studies should attempt to replicate these findings perhaps using more  accessible methods such as transcranial Doppler ultrasonography. If a link between the severity of orthostatic symptoms and ICC can be replicated, this would suggest that patients who experience severe symptoms of OI should be investigated for low levels of ICC. It could then also be investigated whether treatments that raise ICC have ameliorating effects on orthostatic symptoms.S1 File(XLSX)Click here for additional data file.


Hyperuricemia (HUA) is very common in chronic kidney disease (CKD). HUA is associated with an increased risk of cardiovascular events and accelerates the progression of CKD. Our study aimed to explore the relationship between baseline serum uric acid levels and renal histopathological features.One thousand seventy patients receiving renal biopsy in our center were involved in our study. The baseline characteristics at the time of the kidney biopsy were collected from Renal Treatment System (RTS) database, including age, gender, serum uric acid (UA), glomerular filtration rate (eGFR), serum creatinine (Cr), urea, albumin (Alb), 24 h urine protein quantitation (24 h-u-pro) and blood pressure (BP). Pathological morphological changes were evaluated by two pathologists independently. Statistical analysis was done using SPSS 21.0.n = 415), 43.8% (n = 188), and 43.2% (n = 277) in all patients, patients with IgAN and non-IgAN patients, respectively. Serum uric acid was correlated with eGFR , Cr , urea , 24-u-pro , systolic blood pressure (SBP)  and diastolic blood pressure (DBP) . Multivariate logistic regression analysis showed that after adjustment for Cr, age and blood pressure, HUA was a risk factor for segmental glomerulosclerosis  and tubular atrophy/interstitial fibrosis . HUA increased the area under curve (AUC) in diagnosis of segmental glomerulosclerosis.Among 1070 patients, 429 had IgA nephropathy (IgAN), 641 had non-IgAN. The incidence of HUA was 38.8% (Hyperuricemia is prevalent in CKD. The serum uric acid level correlates not only with clinical renal injury indexes, but also with renal pathology. Hyperuricemia is an independent risk factor for segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis. Uric acid is the product of purine metabolism in human body. 70% of uric acid in human body is excreted through kidneys. Uric acid is an intracellular oxidant when it is beyond the physiological range . HyperurHyperuricemia is a common phenomenon in patients with chronic kidney disease (CKD). Previous studies have shown that hyperuricemia was a risk factor for CKD , 9. It cPrevious studies suggested that HUA was associated with tubular interstitial lesions, and high uric acid levels indicated tubular interstitial lesions , 19. HowParticipants receiving renal biopsy in Sichuan Provincial People’s Hospital from January 2010 to December 2016 were screened. Those with adequate information on baseline characteristics in our Renal Treatment System (RTS) database were included in the current study. Exclusion criteria included inability to provide consent, enrollment in competing studies, pregnancy, familial hyperuricemia, transient hyperuricemia, primary gout, transient tubular injury, malignant hypertension, renal cancer, cirrhosis, recent chemotherapy or immunosuppressive therapy, organ transplantation, or dialysis treatment. A total of 1070 individuals  were included in this study. The baseline demographic and clinical characteristics were collected at the time of renal biopsy from RTS database, including age, gender, serum uric acid, glomerular filtration rate (eGFR), serum creatinine, urea, albumin and 24 h urine protein quantitation (24 h-u-pro) and blood pressure. eGFR was estimated with CKD-EPI (CKD Epidemiology Collaboration) creatinine equation [The study was approved by the Ethics Committee of the Sichuan Provincial People’s Hospital . The de-identified data was obtained from RTS database. All patients gave fully informed written consent.Hyperuricemia was defined as a fasting serum uric acid level greater than 420 μmol/L (7 mg/dl) for male and greater than 357 μmol/L (6 mg/dl) for female participants .Renal pathological diagnosis was reviewed independently by two renal pathologists who were blinded to previous pathology reports and patients’ clinical outcomes. Segmental sclerosis of glomerulus was classified as segmental glomerulosclerosis group (S0) and non- segmental glomerulosclerosis group (S1). On the basis of extent of tubular atrophy/interstitial fibrosis, patients were divided into mild injury (T1), moderate injury (T2), and severe injury (T3) according to current literatures  , 23.p value of less than 0.05 was considered statistically significant.Continuous data were presented as mean with standard deviation (SD) or median with interquartile ranges (IQR). Categorical variables were presented as proportions. Continuous data were compared by t-test or one-way ANOVA. Chi-square test was used to compare categorical variables between two groups. Pearson or Spearson correlation analysis was performed to calculate the correlation between uric acid and other clinical indicators. Logistic regression analysis was used to examine whether HUA was an independent predictor of segmental glomerulosclerosis or tubular atrophy/interstitial fibrosis. We also did sensitivity analyses to assess relationship between HUA and segmental glomerulosclerosis or tubular atrophy/interstitial fibrosis in several models. Receiver Operating characteristic Curves (ROC) was used and the area under curve (AUC) was analyzed to test whether HUA can increase the ability to diagnose glomerular segmental sclerosis and tubular atrophy/interstitial fibrosis. All analyses were performed using SPSS, version21.0. n = 415), 43.8% (n = 188), and 43.2% (n = 277) in all patients, patients with IgAN and non-IgAN patients, respectively , the majority of patients (812(75.9%)) did not have segmental glomerulosclerosis  of 1070  patients had biopsy proven IgAN. Patients with IgAN were younger, female predominant, had worse renal function, higher serum albumin level and lower 24 h-u-pro level, as compared to those with non-IgAN. The prevalence of hyperuricemia was 38.8% , Cr , urea , 24-u-pro , systolic blood pressure  and diastolic blood pressure . Uric acid was also correlated with segmental glomerulosclerosis  and tubular atrophy/interstitial fibrosis  in the whole cohort.Participants with segmental glomerulosclerosis had higher level of uric acid and worse renal function than those without segmental glomerulosclerosis in the whole cohort, IgAN and non-IgAN cohort Table . In the Univariate logistic regression analysis showed that hyperuricemia was associated with segmental glomerulosclerosis  and tubular atrophy/interstitial fibrosis . Multivariate logistic regression analysis confirmed this finding   group, focal segmental glomerulosclerosis (FSGS), etc. However, preliminary data analysis revealed that other groups except IgAN had similar clinical features in the current cohort. Moreover, the small number of cases of individual group, is not conducive to the statistical analysis. Finally, we divided all patients into IgAN and non-IgAN and found that the prevalence of HUA was higher in IgAN than in non-IgAN.In the studied cohort, we found that the more serious the histological injury was, the worse renal function were, which were in accordance with previous studies –24. We aIn recent years, with the lifestyle modifications, the prevalence of hyperuricemia (HUA) is increasing, and the prevalence of HUA in Chinese adults ranged from 8.4 to 13.3% , 26. OurThe relationship between HUA and renal pathological features could be explained by the mechanisms how HUA injures the kidneys. HUA can lead to injury in target organs, such as glomerular sclerosis, glomerular hypertension, glomerulosclerosis, interstitial lesions, and acute kidney injury . HUA canDue to the nature of retrospective cross-sectional study, there are some limitations in our study. Firstly, we were unable to draw a causal relationship between uric acid and renal pathological changes. Secondly, some confounders were not collected and included in our analyses, which may have an impact on the results. However, in our study, we found that HUA was associated with glomerulosclerosis and tubulointerstitial injury, which could be helpful in predicting glomerulosclerosis and tubulointerstitial injury in clinical practice especially for patients not going to or not willing to have renal biopsy. The results also raise that HUA as a potential treatment target as recommended by current guidelines might be helpful with renal sclerosis, which needs large scale prospective studies to prove.Hyperuricemia is prevalent in CKD. Uric acid correlates not only with clinical renal injury indexes, but also with renal pathology. Hyperuricemia is independently associated with segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis.