Although 20–60% of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have asthma, the risk factors associated with comorbid asthma are not clear. The aim of the study was to investigate the factors associated with asthma, and develop a practical scoring system to screen asthma comorbidity in CRSwNP patients.This report describes a cross-sectional study with consecutive CRSwNP patients. Two cohorts of CRSwNP patients named “modelling” group and “validation” group were investigated respectively. Logistic regression analysis was performed based on demographic and clinical data collected from patients in the modelling group to determine the risk factors associated with asthma, and establish a scoring system for screening comorbid asthma. Receiver operating characteristic curve was constructed to evaluate the screening system; the optimal cut-off point was established by means of the Yoden Index. The consistency between the diagnosis of asthma by the Global Initiative for Asthma (GINA) criteria and by the screening system was assessed by Kappa value in the validation group.P < 0.001), allergic rhinitis , serum total (T)-immunoglobulin (Ig) E ≥ 69.0kU/L , and blood eosinophil count  ≥ 0.35 × 109/L  were shown to be independent risk factors for asthma in patients with CRSwNP. Based on these variables, a scoring system (FAIE) ranging from 0(no risk) to 6(high risk); was developed. The area under the receiver operating characteristic curve of the system was 0.823, and the optimal cut-off value was 3 points, with sensitivity 83.8% and specificity 68.6% for screening asthma. The asthma comorbidity determined with FAIE score ≥ 3 points in the validation group, was moderately consistent with that defined by GINA , with sensitivity 76.9% and specificity 74.4%.Totally 150 patients in modelling group and 78 patients in validation group were enrolled. Female gender (odds ratio [OR] = 6.4; Female gender, allergic rhinitis, serum T-IgE level, and blood eosinophil count are independent risk factors for asthma comorbidity in patients with CRSwNP, and the FAIE system may be practical for screening comorbid asthma in these patients. Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the nose and paranasal sinuses, which is present in 2–4% of the adult population –3. AboutThe clinical course of asthma in patients with CRSwNP is usually persistent and progressive and more difficult to treat than in asthmatics without CRSwNP , 11. A rAs the persistence of asthma is usually associated with the severity of disease, as reflected by increased bronchial responsiveness and irreversible airflow obstruction in patients with CRSwNP , early iThus, this study aimed to investigate factors associated with comorbid asthma in patients with CRSwNP, based on medical history and clinical examinations; and to develop a scoring system for screening asthma comorbidity in these patients.This was a cross-sectional study, in which patients with CRSwNP aged ≥ 18 years referred to Beijing Tongren Hospital from Nov 2016 to Oct 2018 were enrolled consecutively and grouped as patients with or without asthma.A diagnosis of CRSwNP was confirmed by a rhinologist according to the criteria of the European Position Paper on Rhinosinusitis and Nasal Polyps guidelines (EPOS)  and the 2 was defined as overweight, and ≥ 30 kg/m2 as obesity. Personal history of allergic diseases; including allergic rhinitis, urticaria, eczema; and non-steroidal anti-inflammatory drugs (NSAIDs) hypersensitivity were determined according to typical clinical features and/or specific tests, and the patients were examined for various clinical parameters as detailed below.At the time of enrolment, demographic data and clinical history of all patients were collected using standard questionnaires. Body mass index (BMI) between 25 ~ 29.9 kg/mLogistic regression analysis was used to determine the risk factors of asthma comorbidity in patients based on demographic and clinical data collected, and subsequently a scoring system was established to screen for comorbid asthma. The efficiency of the screening system was evaluated in a second cohort of CRSwNP patients enrolled from Nov 2018 to Dec 2019. The subject selection and study process are shown in Fig. Allergic rhinitis (AR) was determined by typical clinical features  and sensitivity to at least one common aeroallergen , identified by positive skin prick test (SPT) and/or serum antigen-specific immunoglobulin (Ig) E test . UrticarBlood samples were drawn in vacutainer tubes with ethylene diamine tetra-acetic acid.(EDTA) as anticoagulant  and leukocyte counts and eosinophil differentiation in the anticoagulated blood samples were performed on an automatic blood analyzer . Nasal secretions were collected by swabbing the mucosa of middle nasal passage and inferior turbinate and applied to a slide for Wright’s staining . The samAn automatic immunoassay system  was used according to the manufacturer′s directions. The lower limits of detection of serum total (T)-IgE and allergen specific IgE were 2 kU/L and 0.01 kU/L, respectively. Levels of serum T-IgE > 60 kU/L and allergen specific IgE > 0.35 kU/L were considered to be increased . Atopy wFractional exhaled nitric oxide (FeNO) was measured using a nitric oxide analyzer  at a flow rate of 50 mL/s through the oral cavity. The gas was continuously routed into the analyzer via a side port. The procedure was repeated three times and a mean concentration of FeNO was calculated .Nasal polyp tissues were dehydrated, embedded in paraffin, and then cut at 4 μm thickness by using a Leica RM2235 cryostat . The sections were stained by hematoxylin and eosin (H&E) stain and examined by using optical microscopy at a magnification of × 400. For each section, absolute numbers and percentages of eosinophils, neutrophils, plasma cells, and lymphocytes were recorded as mean of 3 non-overlapping regions, and the final evaluation for each patient’s tissue sample was recorded as mean data of 5 sections . Inflamm1)/forced vital capacity (FVC)% and FEV1%predicted.Spirometry  was performed to determine the lung function measurements; including forced expiratory volume in one second  was counted as a reference variable, and given a value of “1”. The score of other variables was obtained by dividing the partial regression coefficient by β of the reference variable [P < 0.05 was considered to be significant.For assessment of risk factor and establishment of screening system (modelling), sample size for each group was determined to be at least 10 times the number of independent risk factors. For validation of the screening system, the sample size for each group was estimated to be at least one half of the sample size needed for modelling. All statistical analyses were performed using the SPSS 23.0 statistical software package . Data were expressed as mean ± standard deviation  or as median and 25th–75th percentiles . T test  and Mann–Whitney U test  were used for comparisons of continuous data between different groups. Categorical variables were analyzed by χvariable , 27 to fvariable . P < 0.09/L, respectively; and eosinophils were found in the nasal secretions of 31.3% of the patients. The median of serum T-IgE was 103.5 kU/L, and atopy was shown in 38.7% of the patients. The level of FeNO was found to be 27  ppb , had lower body mass index (BMI) (P = 0.019), higher prevalence of NSAIDs hypersensitivity (P = 0.001) and allergic rhinitis (P = 0.007), higher levels of eosinophil in blood (P ≤ 0.001) and nasal secretions (P = 0.036), serum T-IgE (P < 0.001), and FeNO (P < 0.001) compared to patients without asthma (Table 1/FVC% and FEV1%pred were significantly lower in patients with asthma (both P < 0.001), and a significantly greater number of these patients took topical corticosteroids (P < 0.001) and leukotriene receptor antagonist (P = 0.031) than patients without asthma  had adult-onset asthma; and 70 patients without asthma. The group of patients with asthma comprised significantly more females (P = 0.120) , history of allergic rhinitis , levels of serum T-IgE  and blood eosinophil count  were found to be independent factors associated with asthma comorbidity in patients with CRSwNP  were optimal for determination of comorbid asthma in patients with CRSwNP  , and 0.35 × 10The area under ROC for the FAIE system was found to be 0.823   Table .Table 7S9/L) were independent risk factors for comorbid asthma in patients with CRSwNP. A scoring system based on these risk factors was also established for screening comorbid asthma, and preliminarily findings suggest that this system may have satisfactory screening efficiency. To the best of our knowledge, this is the first study to systematically evaluate the factors associated with comorbid asthma in patients with CRSwNP, and to establish a system to screen comorbid asthma in these patients.In this cross-sectional study, risk factors associated with comorbid asthma in CRSwNP patients were explored based on medical history and clinical examinations. The study demonstrated that female gender, history of allergic rhinitis, increased levels of serum T-IgE (≥ 69.0 kU/L) and blood eosinophil count (≥ 0.35 × 10Previous studies on risk factors of asthma incidence have shown differences between childhood-onset and adult-onset asthma –31. As aPrevious studies have shown that a female gender, allergic rhinitis, increased serum T-IgE, and blood eosinophil count are associated with increased asthma incidence, and that co-existence of these factors may further increase the risk of asthma. Many epidemiological studies suggest that women are at increased risk of developing adult-onset asthma and also suffer from more severe disease than men , 34, 35.9/L on admission for bronchiolitis was a significant protective factor, and a high blood eosinophil count > 0.45 × 109/L on convalescence was a significant risk factor for asthma in adulthood independently from atopic status [Our findings for blood eosinophil counts and serum T-IgE levels are also in accordance with the findings of Staikūniene and colleagues , who fouc status . Similarc status  have demc status . In the Both allergic and nonallergic rhinitis have been shown to be independent risk factors for adult-onset asthma . InteresMany CRSwNP patients with comorbid asthma have been shown to be characterized by type 2 airway inflammation , 41. RecThe FAIE system developed in the current study was shown to have better screening efficiency for comorbid asthma when the cut-off value of ≥ 3 points was used, both in modelling and validation groups, with sensitivity and specificity of approximately 80% and 70% respectively, and 75% of patients with definite asthma were included. However, the sensitivity of the system to screen comorbid asthma was shown to increase to 98.8% when the cut-off value of ≥ 2 points was used, suggesting that FAIE score ≥ 2 points may be taken as a predictor of comorbid asthma in patients with CRSwNP. Moreover, for CRSwNP patients with FAIE score ≥ 2 points, careful inquiry of asthma symptoms and use of lung function tests may be helpful in identifying patients with comorbid asthma earlier; whereas for CRSwNP patients with FAIE score ≥ 3 points, consultation with a respiratory specialist may be needed based on clinical manifestations and examination of the patients.. The predicted probability of asthma for a given patient, using a logistic regression model rather than just a 0–6 score, would probably have been more accurate if predictors such as T-IgE and blood EOS were included as continuous measures rather than dichotomous measures. For example, in the score calculation, a T-IgE of 68 would give 0 points but a T-IgE of 70 would give 2 points, and thus some information may be lost with this simplification. Nevertheless, there is a case to be made for the advantages of a simplified scoring system that can be easily calculated from information readily obtainable in clinic. The relatively small sample size might also lead to some data deviation and bias of case enrolment, particularly as this was a cross-sectional single-centre study. Furthermore, some factors such as sputum inflammatory cells, access to health care, family history of asthma or atopy, and menopausal status in women, which may be associated with comorbid asthma, were not included. The finding that despite greater topical corticosteroids and leukotriene receptor antagonist use by patients with CRSwNP and comorbid asthma, the levels of eosinophils and IgE were found to be significantly higher in these patients than in CRSwNP patients without asthma, suggests that the influence of greater medication use also needs to be taken into consideration and these findings need to be confirmed in prospective multicentre studies with large sample size in the future.The findings from this study are somewhat limitedFemale gender, history of allergic rhinitis, increased levels of serum T-IgE and blood eosinophil count are important risk factors for development of comorbid asthma in patients with CRSwNP. The FAIE system appears to be a useful and practical screening system for asthma comorbidity, and should be helpful for early diagnosis and prompt management of asthma in patients with CRSwNP. To observe the development of asthma in CRSwNP patients who have not yet been diagnosed with comorbid asthma should be especially helpful in evaluating the efficiency of the system for predicting asthma incidence in CRSwNP patients.


Currently, there is a lack of clinical indicators that can accurately distinguish diabetic kidney disease (DKD) from non-diabetic kidney disease (NDKD) in type 2 diabetes. The purpose of this study was to investigate the diagnostic value of triglyceride and cystatin C (TG/ Cys-C) ratio in DKD. Nowadays, there are few studies on the differential diagnosis of TG/ Cys-C ratio between DKD and NDKD.The clinical data of patients with type 2 diabetes complicated with proteinuria who underwent renal biopsy from January 2013 to September 2019 in 2 hospitals in Xuzhou were retrospectively collected. According to the pathological classification of kidney, 25 patients in group DKD and 34 patients in non-diabetic kidney disease (NDKD) group were divided into two groups. The admission information and blood biochemical indexes of all patients with renal biopsy were collected, and the TG / Cys-C ratio was calculated. Logistic regression analysis was used to analyze the related factors of DKD in patients with type 2 diabetes and proteinuria. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of TG/Cys-C ratio for DKD in patients with type 2 diabetes and proteinuria. Another 37 patients with type 2 diabetes complicated by proteinuria who were treated in the Department of Nephrology, four hospitals in Xuzhou from October 2019 to October 2021 were selected as the research objects. The TG/Cys-C value cut-off value selected in the retrospective study was selected as the boundary point and divided into two groups according to the values of greater than or equal to the tangent point and less than the tangential point. Serum triglyceride and cystatin C levels were measured and TG / Cys-C ratio was calculated. All patients underwent ultrasound-guided fine-needle renal biopsy. The positive rates of DKD diagnosis in the two groups were compared to verify the predictive value of TG / Cys-C ratio in the diagnosis of DKD.P < 0.05).Multivariate Logistic regression analysis showed that TG/Cys-C ratio  was a protective factor for DKD in patients with type 2 diabetes and proteinuria. Diabetic retinopathy  and systolic blood pressure  were independent risk factors for DKD in patients with type 2 diabetes complicated with proteinuria. ROC curve showed that the area under the curve predicted by TG/Cys-C ratio for the diagnosis of DKD was 0.816, the sensitivity was 84%, and the specificity was 67.6%. The tangent value of TG / Cys-C ratio is 2.43. Prospective studies showed that in 37 patients with type 2 diabetes and proteinuria, 29 patients had a TG/Cys-C ratio of less than 2.43. The TG/Cys-C ratio of 8 patients was more than 2.43. Ultrasound guided fine needle aspiration biopsy revealed that 22 of the 29 patients had pathological diagnosis of DKD, sensitivity 91.67%, specificity 46.15%, positive predictive value 75.80%, and negative predictive value 75%.Retrospective study showed that compared with group NDKD, the DKD group had higher systolic blood pressure, higher cystatin C and creatinine, more diabetic retinopathy, longer duration of diabetes, lower hemoglobin concentration, lower glomerular filtration rate, lower cholesterol, lower triglyceride and lower TG/ Cys-C ratio (In type 2 diabetic patients with proteinuria, the ratio of TG/Cys-C has certain predictive value for the diagnosis of DKD. Diabetic kidney disease (DKD) is one of the main microvascular complications of diabetes. Estimated Glomerular Filtration Rate (eGFR) and/or elevated Urine albumin-to-creatinine ratio (UACR) are characterized . In the The clinical data of patients with type 2 diabetes complicated with proteinuria who received renal biopsy from January 2013 to September 2019 in two Hospitals of Xuzhou  were retrospectively collected. The inclusion criteria were as follows: a. T2DM was diagnosed according to the 2013 American Diabetes Association (ADA) criteria ; b.proteFrom October 2019 to October 2021, 37 patients with type 2 diabetes complicated with proteinuria were selected from the Department of Nephrology, four hospitals in Xuzhou . According to the previous retrospective study, the cut-off point value of TG/Cys-C ratio for the diagnosis and prediction of DKD was 2.43. Taking the ratio ≥ 2.43and < 2.43 as the defined values, the subjects were divided into two groups. The TG/Cys-C ratio of 29 patients was less than 2.43, including 20 males and 9 females; The age ranged from 26 to 69 years, with an average of (50.00 ± 11.33) years. TG/Cys-C ratio ≥ 2.43 in 8 patients, 6 males and 2 females; The age ranged from 38 to 70 years, with an average of (53.63 ± 10.25) years. There was no significant difference between the two groups in terms of gender and age, and the two groups were comparable. The inclusion criteria were as follows: a. age ≥ 18 years; b. T2DM was diagnosed according to the 2022 American Diabetes Association (ADA) criteria [The clinical data of all patients from January 2013 to September 2019 were collected, including age, gender, duration of diabetes , whether diabetic retinopathy was found, whether smoking and drinking history, height, weight, systolic blood pressure and diastolic blood pressure were calculated, and body mass index (BMI) was calculated. The blood test indexes of renal biopsy patients were collected, including hemoglobin, fasting blood glucose, albumin, cholesterol, triglyceride, uric acid, creatinine, glomerular filtration rate (eGFR), high-density lipoprotein-c, low-density lipoprotein-c, Cystatin C, glycosylated hemoglobin, fibrinogen (FIB), routine urine chemistry and urinary sediment quantification, and total 24-h urinary protein.TG/Cys-C ratio was calculated, and eGFR was estimated by kidney disease diet improvement (MDRD) formula : eGFR[ml2, measuring seat blood pressure, recording systolic and diastolic blood pressure (mmHg).Develop unified and detailed forms, recording the gender, age, duration of diabetes, height and weight, Body Mass Index (BMI), BMI = body weight (kg)/height (m)All subjects were fasted for 8-10 h, and they should avoid drinking one day in advance and eating high-fat protein diet. 10 ml blood was collected from the median vein of the cubital fossa of the forearm on an empty stomach the next morning . After standing at room temperature for 30 min, 3 ml was centrifuged at 1000 rpm for 5 min, the lower blood cells were removed, the upper serum was taken, the triglyceride level was detected by GPO-POD colorimetry, the serum cystatin C level was detected by immunoturbidimetric method, the creatinine level was detected by creatine oxidase method, and the glycosylated hemoglobin was detected by high performance liquid chromatography. TG/Cys-C ratio was calculated and eGFR was estimated: it was calculated by kidney disease diet improvement (MDRD) formula [All subjects underwent 24-h quantitative detection of urinary protein: empty the bladder at 8 a.m. on the same day, then count the time, collect all urine until 8 a.m. on the next day in a clean container, accurately measure the total amount of urine, record it, stir it evenly, and take 100 ~ 200 ml for examination. In order to prevent deterioration of urination, preservatives  can be added to the bedpan during urine collection. The total amount of urinary protein was detected by turbidimetry.All subjects underwent fundus photography: fundus photography was performed with VISUCAM S224 fundus camera. Two doctors of deputy director of Ophthalmology and above were evaluated.All subjects were examined by ultrasound-guided fine needle renal biopsy: the ultrasonic instrument was Philips EPIQ7 ultrasonic diagnostic instrument, and the probe model was C5-1; The puncture needle shall be American automatic bard biopsy gun, 16 g × 16 cm, the length of biopsy tissue strip was 22 mm. The position, size (long × thick × width) and thickness of renal parenchyma of both kidneys were routinely examined before renal puncture, thickness of renal parenchyma, unit: cm; Laboratory examination of liver and kidney function, coagulation function, platelet count, blood pressure, preoperative discontinuation of anticoagulants. Empty bladder, puncture position: lie prone, abdominal pillow or cushion, fix the position, conduct ultrasonic positioning, routine disinfection and towel laying, after 2% lidocaine anesthesia, use 16G puncture needle under the guidance of ultrasound, enter the needle to the front edge of the capsule of the lower pole of the kidney, pull the trigger, and take out the tissue strip for biopsy. Continuous compression puncture for 6–8 h after operation. All pathological examinations were sent to Nanjing Jinyu Medical Laboratory for pathological diagnosis. Light microscope , electron microscope and fluorescence immunopathological examination were performed respectively, which were analyzed by two experienced pathologists.P < 0.05).SPSS 20.0 statistical software was used to analyze the data. Through the normality test, the data conforming to the normal distribution are expressed in, and the independent sample t-test is used for the comparison between groups. Those that do not conform to the normal distribution are represented by M , and Mann Whitney U test is used for inter group comparison. The number of cases (%) was used for classification and counting data, and the comparison between groups was used χ2 test or Fisher test. Logistic regression analysis was used to analyze the related factors of DKD in patients with type 2 diabetes and proteinuria. The diagnostic value of TG/Cys-C ratio in patients with DKD was evaluated by receiver operating characteristic (ROC) curve, and the cut-off point value was selected. The difference was statistically significant (P < 0.05)  Table .Table 1CP < 0.05)  was a protective factor for DKD in patients with type 2 diabetes and proteinuria. Diabetic retinopathy (OR = 7.054) and systolic blood pressure (OR = 1.041) were risk factors for DKD in patients with type 2 diabetes and proteinuria (9 was a pP < 0.05)  Table .Table 3RP > 0.05). Compared with TG/ Cys-C ≥ 2.43 group, TG/ Cys-C < 2.43 group had a higher proportion of hypertension, and the most obvious increase in systolic blood pressure, lower hemoglobin level, higher serum creatinine level, and lower glomerular filtration rate , which seriously affects the quality of life and life safety of patients. At present, DKD is the main cause of chronic kidney disease and ESRD in the world . timely In this review, we retrospectively reviewed the recent diagnosis of type 2 diabetes mellitus complicated with proteinuria in our city. According to the diagnostic criteria of renal biopsy, 25 cases were diagnosed as DKD and 34 cases diagnosed as NDKD. There are many pathological types in NDKD group, among which membranous nephropathy is the most common pathological type in NDKD group, which is similar to the results reported in other Asian Studies .By reviewing and comparing the clinical indexes of the two groups, it was found that the TG/Cys-C ratio was significantly different in DKD and NDKD patients. TG/Cys-C also considered the status of dyslipidemia and indicators of renal dysfunction in T2DM patients with renal impairment. At present, there is no definite conclusion about the role of TG/Cys-C in differentiating DKD and NDKD. Studies have shown that hyperlipidemia is an independent risk factor for the progression of DKD . In vivoPrevious meta-analysis  showed tThis retrospective study shows that in patients with type 2 diabetes and proteinuria, DKD patients have higher blood pressure and creatinine levels, lower glomerular filtration rate and hemoglobin level. This indicates that the level of renal function in patients with DKD is relatively poor in the course of diabetes mellitus. Besides the combined effect of renal hemodynamic disorder, the sensitivity of insulin receptor is reduced, the function of islet is reduced, and the time of exposure to high glucose environment is prolonged. This leads to the increased risk of DKD in patients . All theIt is generally believed that the duration of diabetes, the absence of diabetic retinopathy, hematuria or unexplained acute kidney injury may be a useful indicator of renal biopsy in patients with type 2 diabetes combined with dominant proteinuria . PreviouIn order to evaluate the diagnostic value of TG/Cys-C ratio for DKD in patients with type 2 diabetes mellitus and dominant proteinuria, the ROC curve was constructed in this retrospective study. The results showed that the area under the DKD curve predicted by the TG/Cys-C ratio was 0.816, corresponding sensitivity and specificity were 84% and 67.6%, respectively, and the cut-off point value was 2.43. The results of this study showed that when the TG/Cys-C ratio was lower than 2.43 in patients with type 2 diabetes and proteinuria, it was suggested that the possibility of diagnosing DKD was too large. When the TG/Cys-C ratio was higher than 2.43, we should be alert to the possibility of combining NDKD. Further renal biopsy was recommended to make clear diagnosis and guide treatment.In order to further verify the predictive value of TG/Cys-C ratio for the diagnosis of DKD, based on the results of previous retrospective studies, a prospective study was carried out in newly enrolled type 2 diabetic patients with proteinuria by taking the cut-off point value TG/Cys-C of the ratio as the defined value. The results showed that among the 37 patients with type 2 diabetes mellitus combined with proteinuria, TG/ Cys-C < 2.43 in 29 patients and TG/ Cys-C ≥ 2.43 in the other 8 patients. We analyzed the clinical characteristics of patients in the two groups, and the renal function level of patients in the TG/ Cys-C < 2.43 group was worse. We analyzed the pathological characteristics of renal biopsy in patients with type 2 diabetes. (a) DKD, defined by the presence of suggestive glomerular lesions like nodular sclerosis, diffuse mesangial sclerosis, mesangial expansion, basement membrane thickening, arteriolar hyalinosis, micro aneurysms and exudative lesions . (b) NDKIn summary, the low level of TG/Cys-C is a protective factor for DKD in type 2 diabetic patients with proteinuria. TG/Cys-C ratio has important clinical guiding significance for the prediction and diagnosis of DKD.This study has some limitations. Firstly, information bias cannot be avoided in this retrospective study. All patients' medical history data are from the internal electronic medical record system of the hospital, and there may be poor accuracy of medical history records. In addition, blood pressure measurement is greatly affected by emotion or activity, which is easy to cause blood pressure fluctuation and data deviation. Secondly, due to the limitation of clinical sample size, the cases collected in this study are only within the scope of this city and can not represent the population in all regions of the country, which limits the universal applicability of the research results to other groups. Finally, the occurrence and development process of DKD and NDKD diseases is extremely complex. There may be other influencing factors that have not been explored in the research, and more in-depth exploration is needed in the future.


Background: Sepsis-associated encephalopathy (SAE) is associated with high morbidity and mortality. Hemodynamic dysfunction plays a significant role in the incidence and mortality of SAE. Therefore, this study aimed to explore the relationship between hemodynamic indicators and SAE. Methods: 9033 patients with sepsis 3.0 were selected in a prospective study cohort. The LASSO regression model was used to select characteristic variables and remove the collinearity between them. In addition, a generalized additive model was used to find the optimal hemodynamic index value for patients with SAE. Multivariate logistic regression models, propensity matching scores, inverse probability weighting, and doubly robust estimation confirmed the reliability of the study results . Results: A mean arterial pressure ≥ 65 mmHg, systolic blood pressure ≥ 90 mmHg, and lactate levels ≤ 3.5 mmol/L decrease the incidence of SAE, whereas a mean arterial pressure ≥ 59 mmHg and lactate levels ≤ 4.5 mmol/L decrease the 28-day mortality in patients with SAE. Conclusions: The hemodynamic indices of patients with SAE should be maintained at certain levels to reduce the incidence and mortality in patients with SAE, such that the mean arterial pressure is ≥65 mmHg, lactate levels are ≤3.5 mmol/L, and systolic blood pressure is ≥90 mmHg. These hemodynamic indicators should be targeted in patients with SAE. Sepsis-associated encephalopathy (SAE) is a diffuse cerebral dysfunction caused by infection . ApproxiSepsis causes tissue hypoperfusion and metabolic dysfunction, leading to multiple organ disorders . CerebraAccording to the third international consensus definition for sepsis and septic shock, a mean arterial pressure > 65 mmHg is essential to ensure multiple organ perfusion in patients with sepsis . HoweverWe retrospectively collected data from the Medical Information Mart for Intensive Care IV (MIMIC-IV 1.0) and the multicenter database eICU Collaborative Research Database (eICU-CRD v2.0). The MIMIC-IV includes 69,619 ICU admissions from 2008 to 2019, and eICU-CRD covers 200,859 ICU admissions from 2014 to 2015 at 208 U.S. hospitals. The study team completed the Collaborative Institutional Training Initiative Examination and obtained the certification number 33690380 on 8 October 2019. The Massachusetts Institute of Technology Review Committee approved the above databases. Because this was a retrospective study, patients’ written informed consent was not required. The personal information of all patients was identified and includes demographic information, site of infection, microbiology type, vital signs, laboratory parameters, Glasgow Coma Scale (GCS), sequential organ failure assessment (SOFA) score, and other patient data. The raw data were extracted by employing structure query language (SQL) with Navicat and further processed using R software.The study population was compliant with the diagnostic criteria of sepsis 3.0. . We inclDemographic characteristics, including age and gender, and coexisting illnesses, including hypertension, diabetes, respiratory diseases, and renal diseases, were collected for all patients. Additionally, we recorded the infection site and the microbiological infection type for sepsis patients. The worst vital signs and laboratory parameters were extracted in the hospital. Patient’s disease severity scores, including SOFA and GCS, were gathered. Moreover, data on the types of vasopressor drugs used during hospitalization and whether mechanical ventilation was used were collected. The prognostic indices of patients, including length of hospital stay, hospital mortality, and 28-day mortality were retrieved. Patients with repeated ICU admissions were excluded, and only the first admission was recorded.The continuous variables were represented as the median and interquartile range (IQR). They showed a skewed distribution and were tested by the Shapiro–Wilk test. The Mann–Whitney U test was used to compare the continuous variables between the SAE and non-SAE groups, and the survival and non-survival groups, while the categorical variables were represented as counts and percentages and compared using Fisher’s exact test.The LASSO regression model was used to select the characteristic variables in the high-dimensional sparse model and remove the collinearity between characteristic variables . The chap-value < 0.05 was considered statistically significant.We used the propensity score matching to match the covariates that were different between 15,825 and 5310 patients with sepsis were extracted from the MIMIC-IV and eICU databases, respectively, based on the inclusion and exclusion criteria. There were 5861 patients (64.89%) in the SAE group and 3172 patients (35.11%) in the non-SAE group. We excluded patients with sepsis who did not use vasopressors .Klebsiella infection, Escherichia coli infection, Pseudomonas aeruginosa infection, Acinetobacter baumannii infection, and fungus infections than patients in the non-SAE group. Additionally, patients with SAE had higher heart and respiratory rates than those with non-SAE. Although, systolic blood pressure, diastolic blood pressure, and mean arterial pressure were lower in the SAE group than in the non-SAE group. Moreover, the patients with SAE had a higher hospital mortality, 28-day mortality, and length of hospital stay than those in the non-SAE group. In addition, more patients with SAE were treated with mechanical ventilation.p < 0.05 in the original cohort, excluding systolic blood pressure, diastolic blood pressure, mean arterial pressure, lactate levels, length of hospital stay, hospital mortality, and 28-day mortality   .The consistent results of multivariate logistic analysis, propensity score matching, IPW, and doubly robust estimation showed that a systolic blood pressure ≥ 90 mmHg, a mean arterial blood pressure ≥ 65 mmHg, and lactate levels ≤ 3.5 mmol/L were protective factors against the incidence of SAE. After propensity matching, we found differences in systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, and lactate levels between the SAE and non-SAE groups. Diastolic blood pressure was not supported by the multivariate logistic analysis, propensity matching score, IPW, and doubly robust estimation model . The SMDn = 5022) and non-survival groups (n = 839) (p < 0.05) in many characteristic variables. Using LASSO regression, 36 characteristic variables of the minimum model and 19 characteristic variables of the most streamlined model having p < 0.05 were selected  . The resselected   as it was a retrospective observational study, the results of this work can only explain an association, rather than a causal relationship, between the hemodynamic indices and SAE; (2) although we used LASSO regression, logistic regression, propensity score matching, propensity score IPW, and doubly robust estimation to remove confounding factors, there were many other confounding factors that may cause information bias and deviation from the study results; (3) the definition of SAE in this study refers to the methods of previous high-quality retrospective studies on SAE, and the lack of a gold standard for SAE diagnosis may lead to the inaccurate selection of patients with SAE. Despite these limitations, the large cohort study of multiple models provides a reference value for clinicians in the hemodynamic management of patients with SAE. At last, this study used only a single value for blood pressure and lactate values in patients with sepsis, whereas it may be more meaningful to observe their dynamic changes.We should implement better management of blood pressure and lactate levels in patients with SAE, especially for those that need vasopressors. We recommend that the mean arterial pressure of patients with sepsis should stay at ≥65 mmHg, lactate levels at ≤3.5 mmol/L, and systolic blood pressure at ≥90 mmHg to ensure proper cerebral perfusion and reduce the incidence and mortality in patients with SAE. It would be more meaningful, however, to dynamically monitor blood pressure and lactate levels. The results of this study provide a reference for clinicians to prevent and treat patients with SAE. Future randomized trials could also adopt the results of this study as a reference target.


Essential hypertension is a polygenic cardiovascular disease that is associated with maladaptive metabolic changes. Acupuncture as a non-pharmacologic intervention is used to lower blood pressure and improve metabolic dysfunction. However, such effects have not been clinically characterized. We will conduct a randomized clinical trial to evaluate the antihypertensive effect of acupuncture among patients with essential hypertension and determine the associated metabolic improvements. This study is a phase II, two-arm, randomized, sham-controlled trial , in which biospecimens will be collected for metabolic profiling. A total of 64 patients with a clinical diagnosis of essential hypertension will be randomly assigned to either the acupuncture or the sham acupuncture group in a 1:1 ratio. All participants will receive 10 treatments over 4 weeks, with three sessions per week for the first 2 weeks and two sessions per week for the remaining weeks. The primary outcome is the change of the systolic and diastolic blood pressure measured by the 24-h ambulatory blood pressure monitoring from baseline to 4 weeks. Secondary outcomes include the circadian rhythm of blood pressure, sleep quality measured by the Insomnia Severity Index, cognitive function measured by the Montreal Cognitive Assessment, and others. Fasting blood serum and urine samples will be collected at baseline and 4 weeks for targeted and untargeted metabolomics analysis. We will use the mixed-effects model and other related bioinformatics approaches to analyze the clinical and metabolome data. This metabolomic-based trial will provide important clinical data regarding the efficacy of acupuncture for essential hypertension to better inform evidence-based care delivery for hypertension patients. Moreover, the findings will offer important insights into the mechanism of action of acupuncture for hypertension by revealing its effect on metabolism. The results of this study will be used to inform the design of a statistically powered, multicenter, randomized trial. We will publish the study findings in peer-reviewed journals. The ethical approval of this study has been reviewed and approved by the Sichuan Regional Ethics Review Committee on Traditional Chinese Medicine (ID: 2021KL-006). The outcomes of the trial will be disseminated through peer-reviewed publications. Essential hypertension (EH), or primary hypertension, characterized by sustained blood pressure elevation, is a complex polygenic cardiovascular disease associated with a high morbidity and mortality rate. Over one billion people worldwide live with EH . EpidemiLifestyle factors including food and diet, body weight, daily activity, and stress emerge as modifiers of blood pressure. Exercise and stress management that directly target lifestyle factors have been shown crucial in blood pressure management and metabolic health , 13. AcuOur pilot studies highlighted that the antihypertensive effect of acupuncture was associated with metabolic improvements in EH patients, possibly through modulating fatty acid metabolism and the citric acid cycle –25. BuilThe study protocol conforms to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 statement and standards for reporting interventions in clinical trials of acupuncture (STRICTA) , 27. TheThis study is a randomized controlled trial conducted at the Chengdu University of Traditional Chinese Medicine and the Geriatric Hospital of Sichuan Province, Chengdu, China. A total of 64 patients with essential hypertension and 10 healthy subjects will be recruited. 64 patients will be randomly allocated in a 1:1 ratio to either the acupuncture or sham acupuncture group. Patients will receive 10 treatments over 4 weeks. The primary outcome is the 24-h average blood pressure measured with 24-h blood pressure monitoring (24-h ABPM) at 4 weeks. Secondary outcomes include blood pressure measured at 8 weeks, the 24-h circadian rhythm of blood pressure, the sleep quality measured by the Insomnia Severity Index (ISI), cognitive function measured by the Montreal Cognitive Assessment (MoCA), TCMBC, health-related quality of life, patient's treatment expectancy, and adverse events. The details of the study design are shown in We will enroll participants from the Chengdu University of Traditional Chinese Medicine, the Geriatric Hospital of Sichuan Province, and their local communities. We will use different recruitment strategies such as posters, leaflets, social media, and free medical consultations to inform and recruit potential patients. We will also enroll patients from physician referral.The patient will be diagnosed with essential hypertension according to the 2017 ACC/AHA Clinical Practice Guidelines .(1) Between 18 to 60 years old, (2) free from any kind of drugs at least 2 weeks before inclusion, (3) naivety to acupuncture treatment for hypertension, and (4) willingness to participate in this study and provide written conformed consents.(1) With serious primary diseases such as cardiovascular, cerebrovascular, kidney and hematopoietic system, or metabolic diseases such as diabetes and thyroid dysfunction; (2) with skin diseases and skin damage on the skin or acupoints of the test site; (3) women with pregnancy or lactation or have pregnancy plans in the past year; (4) with history of epilepsy and obstructive sleep apnea syndrome; (5) with history of severe mental disorders or psychoactive substance dependence; (6) with abnormality in a laboratory test of blood biochemistry or with contagious risks; (7) used to suffer from acute diseases in recent 2 weeks, such as high gastritis or fever; (8) once received acupuncture treatment; (9) participating in other clinical trials.Healthy subjects of similar age, body mass index (BMI), and gender will be recruited mainly from the local communities. These participants have no functional or organic disorders, are not suffering from the common cold or other conditions, and have not received acupuncture treatments or taken medications within the past three months. In addition, alcoholics, smokers, and women with pregnancy or lactation will not be included.A cardiovascular physician will confirm the diagnosis of interested participants based on the 24-h ABPM test . A clinical research coordinator (CRC) will screen the participant based on the eligibility criteria, and pre-consent for a physical examination and eligibility laboratory tests. The eligibility of an individual who is deemed potentially eligible per CRC will be further confirmed by a study physician. The CRC will consent and register the participant under the patient information system at the Geriatric Hospital of Sichuan Province.An independent researcher who will not be involved in contact with patients generates the random sequence in R . Each raAll the participants, outcome assessors, and biostatisticians will be masked to group allocation during the study period. Although acupuncture practitioners will not be masked in this trial, they are not involved in any process of outcome assessment. Furthermore, all treatment sessions and outcome assessments will be conducted in a quiet, separate room for each patient to restrict communications between participants and ensure subject blinding. During treatment, patients will be instructed by acupuncture to lie in a supine position and be covered by a light blanket to enhance blinding.Participants in both groups will receive 10 sessions of acupuncture treatment throughout 4 weeks, three times per week for weeks 1 and 2, and twice per week for weeks 3 and 4. The treatment protocol was developed by consensus with experienced acupuncture physicians and based on our previous studies , 29, 30 de-qi sensation. We will use Hwato therapeutic apparatus  to connect the needles at the two acupoints located in the ipsilateral limb. The frequency will be 60/100 Hz, and the electric current will vary from 1.0 to 2.0 mA until the patients feel comfortable. The acupuncture needles will be retained for 25 min in each session. In addition, all participants will receive lifestyle education on how to improve blood pressure through diet, weight control, and exercise.Patients in the acupuncture group will receive electroacupuncture treatment. Sterile disposable acupuncture needles  will be used for treatment. The manipulations are as follows: Acupuncture needles will be inserted into acupoints at a depth of 20-25 mm after skin disinfection using an alcohol wipe. After insertion, needles will be manually manipulated by gentle lifting, thrusting, and rotating until to achieve the Patients in the sham acupuncture group will receive a non-invasive sham acupuncture treatment . AcupuncThe primary outcome is the change in mean 24-h systolic and diastolic blood pressure at week 4. The 24-h ABPM is a common and objective measure of blood pressure validated in clinical practice and research, which provides accurate estimates of blood pressure throughout the day , 33. We The ISI is a validated patient-reported outcome of insomnia designed to specifically assess the impact of insomnia on daytime functioning and the severity of associated distress . The ISIThe MoCA is a rapid screening instrument to identify mild cognitive impairment. The validity and reliability of the MoCA have been demonstrated in previous studies , 38. MoCThe SF-12 is a generic and well-established health-related quality of life measure that has been commonly used in both general populations and various patient cohorts . The SF-TCMBC is a validated tool of patient categorization according to Chinese medicine diagnosis, which has been widely applied in practice by Chinese medicine practitioners . TCMBC hThe Acupuncture Expectancy Scale (AES) is a 4-item instrument developed to measure outcome expectancy in the context of the acupuncture treatment . It has We will collect fasting serum and urine samples before acupuncture treatment and on the second day of the final treatment from 8:00–9:00 a.m. We will also collect biospecimens from healthy subjects. Participants are required to (1) be free from the intake of alcohol, refresher drinks, coffee, amino acids, hormone, and vitamin supplements 48 h before sampling, (2) and maintain a regular diet and sleep habits, (3) avoid strenuous exercise 24 h before sampling; and (4) be fasting for 12 h before sampling. Fasting blood samples will be collected into vacutainer tubes with a coagulant; meanwhile, urine samples will be collected in a urinal cup. Both blood and urine samples will be immediately cooled to 4°C. Then these samples will be centrifuged within 2 h at 1500 rpm for 15 min. When completed, serum and urine samples will be separated and transferred to new vials. These samples will be finally stored frozen (−80°C) until metabolomic analysis preparation.Serum samples will be pre-processed, divided for the available targeted and non-targeted metabolomics methods, and dried. Samples will then be reconstituted and analyzed using metabolomic platforms. The preliminary targeted analysis will consist of mining for metabolites in the Krebs Cycle and others identified in previous studies –25. SecoPatient safety will be monitored throughout the trial, with reporting of adverse events (AEs) and serious adverse events (SAEs), such as subcutaneous hemorrhage, vertigo, stroke, or even death. All AEs/SAEs will be recorded carefully and reported immediately in the case report form.Zα = 1.96), and the power of the test was set at 0.9 . A total of 64 participants will be required in this study (32 in each group), including compensation for an anticipated dropout rate of 20%. Additionally, 10 healthy participants will be recruited as the healthy control group.According to preliminary data from our pilot study, acupuncture was associated with a 9.6-mmHg (δ) greater reduction of 24-h average systolic blood pressure and a 7.7-mmHg greater reduction of 24-h average diastolic blood pressure as compared with sham acupuncture. Conservatively, we hypothesized that acupuncture is associated with a 7.5 mmHg reduction (σ) in 24-h systolic blood pressure compared to sham acupuncture. The significance level was set at 0.05  in SIMCA-P  and the MetaboAnalyst  to fulfill the identification of differential metabolites between groups. All statistical tests will be two-sided, and statistical significance will be set at 5%.Clinical data will be analyzed with SPSS 24.0 software . Continuous variables will be presented as mean and SD or as median and interquartile if they are not normally distributed. The baseline variables will be analyzed by the independent-samples t-test and Mann–Whitney U test, where appropriate. Categorical data will be presented as percentages. We will use the mixed-effects model to compare the effect of acupuncture vs. sham acupuncture on blood pressure from baseline to 4 and 8 weeks. The fixed effects are treatment arm, time, groupAcupuncture reduces stress and is widely used as a non-pharmacological treatment for cardiovascular diseases and metabolic disorders , 47. HowTill now, the role of acupuncture in blood pressure management remains unclear. Our previous systematic review of randomized clinical trials found inconsistent results concerning the effect of true vs. sham acupuncture on blood pressure, due to the risk of bias associated with sample size, control arms, and treatment population , 20, 48.In addition to blood pressure and metabolic profile, this study measures the co-occurring sleep and cognitive symptoms, and health-related quality of life in EH patients, which is seldom addressed by previous studies. Insomnia and sleep disturbances are common and bothersome among EH patients . On the This study will also contribute to the identification of potential biomarkers predicting a more pronounced response to acupuncture among EH patients. The pathogenic process of EH is multifactorial; precision treatment targeting a specific signaling pathway or a certain subtype of the population is developed in the conventional treatment paradigm. However, it remains unexplored in non-pharmacologic treatment. Our pilot study showed that specific metabolic pathways are involved in the regulation of blood pressure by acupuncture, which is promising in outcome prediction during the acupuncture treatment , 25. LevThe studies involving human participants were reviewed and approved by the Sichuan Regional Ethics Review Committee on Traditional Chinese Medicine, which belongs to the Regional Ethical Review Committee of Traditional Chinese Medicine in Sichuan province (reference number: 2021KL-006). Written informed consent will be obtained from all participants.MY conceived and designed the study. PZ, FZ, YC, HP, XH, WJ, TD, and FL participated in the design of the study. PZ, YQ, HP, MS, and XH will carry out the acupuncture treatment for patients. In this study, PZ, YQ, YC, and JC screen, assess, and enroll patients. YC and JC are responsible for collecting the data. MY and PZ drafted the manuscript. FZ, YC, and TD revised the manuscript. All authors have read the manuscript and approved the publication of the protocol.This trial was finally supported by the grant from the National Natural Science Foundation of China (No. 81904304), the Young Elite Scientists Sponsorship Program by the CAST (YESS) (No. CACM-2019-QNRC1-04), and the Technical Development Fund of Wuxi City (No. WX18IIAN043). The funding source had no role in the design of this study and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results.MY declared that the funding grants supporting the current work were obtained before he joined MSKCC in 2020. The affiliations reflect both the previous and current institutes that he is affiliated with. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Our aim was to compare cerebrovascular and systemic vascular function between older adults with and without mild cognitive impairment (MCI), and to determine which measures of vascular function best predict the presence of MCI.2, and responsiveness to changes in blood pressure (%∆MCAv/%∆MAP). Systemic vascular function was assessed by flow-mediated dilation (FMD) and stiffness by pulse wave velocity (PWV).In 41 adults with MCI and 33 adults without MCI (control) we compared middle cerebral artery velocity (MCAv) and cerebrovascular pulsatility index (PI) at rest, cerebrovascular reactivity to COp = 0.76) and relative cerebrovascular reactivity to CO2 (p = 0.34) was similar between MCI and control. When age was included as a covariate the significant difference in cerebral PI between groups was lost. PWV was higher (13.2 ± 2.2 vs. 11.3 ± 2.5 m s−1) and FMD% (4.41 ± 1.70 vs. 5.43 ± 2.15%) was lower in MCI compared with control. FMD% was positively associated with PI across the cohort. Logistic regression analysis indicated that FMD and PWV significantly discriminated between MCI and controls, independent of age, whereas the inclusion of cerebrovascular measures did not improve the predictive accuracy of the model.Cerebrovascular PI was higher in MCI compared with control (mean ± SD: 1.17 ± 0.27 vs. 1.04 ± 0.21), and MCI exhibited a lower %∆MCAv/%∆MAP (1.26 ± 0.44 vs. 1.50 ± 0.55%). Absolute (These findings raise the possibility that early changes in systemic vascular stiffness and endothelial function may contribute to altered cerebrovascular haemodynamics and impaired cognitive function, and present potential targets for prevention and treatment strategies in people with MCI.The online version contains supplementary material available at 10.1007/s00421-022-04956-w. The prevalence of dementia is increasing and is expected to directly affect 74 million adults worldwide by 2030 WHO . Prevent2 and perturbations in blood pressure, i.e. dynamic autoregulation, are conflicting  ultrasonography to investigate the intracranial arteries, there is evidence that the velocity of cerebral blood flow (CBFv) is lower, indicative of chronic hypoperfusion, in adults with MCI , and elevated pulse wave velocity (PWV), are associated with poor cognitive performance and steeper declines in cognition with age  and control participants (n = 33). Those with MCI were recruited through the NeuroExercise project  and was approved by the institutional human research ethics committees. Participants provided written informed consent and were screened to ensure they met the inclusion criteria prior to participation.This study included a comparison of adults with MCI , and heart rate (HR) which were recorded throughout the study session. After resting supine measurements were obtained, cerebrovascular CO2 reactivity was assessed using a breath-hold test. Participants then performed a repeated stand-to-sit test for the determination of cerebral pressure-flow responsiveness. Baroreflex sensitivity was also assessed during the repeated stand-to-sit procedure. Following this, participants underwent a further 15 min of supine rest prior to assessments of peripheral and central blood pressure, wave reflection characteristics, and carotid-femoral PWV. Finally, participants underwent a test of brachial artery FMD as a measure of systemic endothelial function. All assessments were conducted in a quiet, temperature controlled (23 ± 0.5 °C) laboratory.After screening, all participants attended the laboratory on a single occasion to undergo a series of cerebrovascular and systemic vascular assessments. Participants refrained from alcohol and exercise for 24 h and caffeine for 12 h before the session and continued to take prescribed medication. Participants were fitted with instruments to measure middle cerebral artery blood flow velocity (MCAv), mean arterial blood pressure (MAP), end-tidal carbon dioxide (PVs − Vd)/Vmean]  was calculated using Gosling and King’s equation [PI =  was calculated by subtracting the average over the last two breaths before the breath-hold from the peak PETCO2 response immediately after the breath-hold. The first two breath-hold manoeuvres were used to familiarise participants with the procedure (Tancredi and Hoge ETCO2 as absolute (∆MCAv/∆PETCO2) and relative (%∆MCAv/∆PETCO2) responses.Cerebrovascular reactivity was assessed as the MCAv response to changes in PETCO2. Whereas for HR responses, maximum values were identified during the stand phase and minimum values during each sit phase. For each transition, the response of each variable was calculated using the delta (sit − stand). The transition delta responses were also expressed as a percentage of the stand phase values (%∆), and the ratio of %∆MCAv/%∆MAP was calculated for each transition as previously reported . This same protocol has previously been used in older adults . Heart rate was monitored by ECG and blood pressure was measured continuously at the left middle- or index-finger using photoplethysmography . Participants breathed through a leak-free respiratory mask , and expired air was continuously sampled for the determination of PETCO2. All variables were sampled at 1000 Hz and stored . Time-aligned signals were then resampled to second-by-second (1 Hz) for visual inspection and analysis.MCAv was measured continuously using transcranial Doppler ultrasonography (TCD) where a 2 Hz probe was placed over the right temporal window and fixed at a constant angle with a customised headband . The MCAv signal was identified according to standardized criteria guided by signal depth, velocity and wave characteristics  and backward (Pb) pressure waveforms, which were expressed as the wave reflection magnitude . This method assumes a triangular-shaped flow wave approximated from the estimated aortic pressure wave  between the carotid and femoral sites multiplied by 0.8, divided by the time delay (s) between the pulse waves . These tests have previously been described in detail . Our laboratory has previously reported a between and within day coefficient of variation (CV) for FMD% of < 10%  and cerebral (%MCA/%MAP and PI) measures of interest were able to discriminate between MCI and control. Age was entered at Step 1, followed by the systemic and cerebral variables of interest at Step 2. Large confidence intervals were observed for the odds ratio for PI. To address this, PI scores were subsequently categorised as high versus low . However, treating PI as a categorical variable did not affect the results and thus raw values are reported.Based on the mean effect extracted from a pooled dataset of > 500 MCI and control participants across multiple studies .Pearson’s correlation coefficients were used to examine the relationships between cerebrovascular and systemic function responses in the MCI and control groups. The effect size is reported as low if the value of r is around 0.1, medium if .5 Cohen . Statistn = 41, CON: n = 33) was available for the analysis of MoCA scores and other participant characteristics, as well as the assessment of central blood pressure and augmentation index. Due to technical difficulties in obtaining reliable MCAv or finger blood pressure signals during the sit-to-stand test, there were seven missing cases from the MCI group ; and an additional four missing MCI cases for the cerebrovascular reactivity dataset because of difficulties performing the breath hold manoeuvre . For the assessment of pulse wave velocity there were four missing cases from the MCI group and three missing cases from the CON group  because a reliable 10 s carotid artery pulse wave signal could not be obtained. Flow mediated dilation could not be assessed in two MCI cases due to poor ultrasound image quality . Analyses were carried out with all available data without substitution or imputation for missing cases.A complete dataset (MCI: p = 0.001); and the MCI group also had a significantly lower MoCA score (p < 0.001). The significant difference in MoCA scores between groups remained when accounting for age (p < 0.001). Resting heart rate, peripheral blood pressures, and BMI were all similar between groups. There was a difference in aspirin medication use between MCI and controls (p < 0.001), and higher beta blocker use in MCI (p = 0.06); but the use of other medications was similar between groups.Participant characteristics are presented in Table p = 0.03), but this effect was lost when accounting for age as a covariate (p = 0.35). Cerebral pressure-flow responsiveness and cerebrovascular reactivity to CO2 are presented in Tables ETCO2 and MAP were not different between MCI and control groups. The MCI group showed a lower %∆MCAv/%∆MAP response than the control group (p = 0.048). When accounting for age the difference in the %∆MCAv/%∆MAP was lost (p = 0.08).Cerebrovascular outcomes are presented in Table ETCO2 was similar between groups during the breath-hold test. While the change in MCAv was significantly higher in control compared to MCI (p = 0.014), the peak MCAv also tended to be higher in control compared to MCI, but this did not reach statistical significance (p = 0.064). The cerebrovascular conductance (CVC) reactivity to CO2 (p = 0.761) and relative cerebrovascular reactivity (p = 0.341) was similar between MCI and control groups. Findings for cerebrovascular reactivity were unaffected when accounting for age as a covariate (p = 0.75).The change in Pp = 0.002). Brachial artery FMD% was lower in MCI compared to control (p = 0.030). When accounting for age as a covariate, the significant differences in both PWV (p = 0.004) and FMD% (p = 0.02) remained. Across both cerebrovascular and systemic vascular outcomes, we observed similar differences between MCI and control groups when the male and female cohorts were considered separately (Refer to Online Resource: Supplementary Table 1). While some of the group differences were no longer statistically significant, the magnitude of the differences in means were similar to the effects reported in the full cohort.Indices of central blood pressure, wave reflection characteristics, pulse wave velocity and vascular function are presented in Table χ2(1) = 8.601, p = 0.003, Nagelkerke R2 = 0.178 (Table χ2(4) = 17.98, p = 0.001, Nagelkerke R2 = 0.477). However, only the systemic measures contributed significantly to the model. Accordingly, a second logistic regression analysis was performed, excluding the cerebral measures.Age significantly predicted group membership, accounting for 17.8% of the variance (78 Table . Adding Including systemic vascular outcomes only (FMD and PWV) accounted for 72.3% of the sample variance Table . For eacn = 71, r = 0.28, p = 0.017). Cerebrovascular PI was associated with systolic blood pressure in the pooled cohort , and this association was stronger in MCI  than in control . Cerebrovascular PI was also negatively associated with diastolic MCAv at rest when examining the pooled cohort . These findings are shown as an Online Resource . When considered separately, this association remained significant in control  and in MCI . We found no significant associations between PWV and cerebrovascular parameters in MCI or control groups (p > 0.05). FMD% was positively associated with PI in the pooled cohort , and this association was strong in MCI , but not in control .Correlations between MoCA scores and the cerebral and systemic outcomes are presented as an Online Resource (Supplementary Table 2). MoCA score was associated with FMD in the pooled cohort . We observed a higher cerebral PI and lower cerebrovascular responsiveness to changes in blood pressure (stand–sit test) in adults with MCI compared with control participants. For systemic vascular outcomes we observed higher aortic stiffness (PWV) and lower systemic endothelial function (FMD) in adults with MCI compared to control. When controlling for age, the observed differences in cerebral outcomes were lost and only systemic vascular outcomes (FMD and PWV) differed between MCI and control. This suggests that MCI is likely responsible for the differences we observed in systemic vascular outcomes.Resting cerebral blood velocity (MCAv) was similar between groups in this study. Previous studies have shown that cerebral blood flow gradually decreases across the spectrum of cognitive impairment, particularly when investigations include adults across a wide spectrum of disease severity . This is in line with the findings of De Heus et al.  and endothelial dysfunction (FMD) predicted the presence of MCI in this study, independent of age. In contrast, cerebrovascular outcomes did not distinguish between MCI and healthy adults. Interestingly, when we accounted for age differences between the MCI and control groups, any differences in cerebrovascular function were lost. This is in line with previous findings showing no significant differences in cerebrovascular outcomes in healthy adults who are elderly (65 + years) and older-elderly (74 + years) Below is the link to the electronic supplementary material.


Spearman correlation analysis was used to analyze the correlation between UACR and SOD. Univariate and multivariate logistic regression analyses were used to screen for the risk factors for HM. Our research included 556 patients in the NHM group and 134 patients in the HM group. Spearman correlation analysis showed a negative correlation between SOD and UACR (P < 0.001). Multivariate logistic regression analysis showed SOD was an independent protective factor in hypertensive patients with HM. In hypertensive patients, a substantial, negative correlation between SOD and early renal damage was found, suggesting that SOD may protect renal function.Oxidative stress had been linked to hypertensive renal impairment in previous investigations. Superoxide dismutase (SOD) was a clinically available oxidative stress biomarker. The association between SOD and the microalbuminuria in hypertensive patients has not been established. From January 2017 to December 2018, data on 690 patients with essential hypertension were collected retrospectively at Shandong Provincial Qianfoshan Hospital. Patients were divided into hypertension with microalbuminuria group (HM) and hypertension without microalbuminuria group (NHM). Clinical data from patients were collected and compared between the two groups.  An estimated 1.28 billion people between the ages of 30 and 79 are affected with hypertension worldwide, with two-thirds of them residing in low- and middle-income nations. Unbelievably, 46% of hypertension patients are totally ignorant of their condition2. As a result, the harmful effects of hypertension on target organs such as heart, brain, and kidney become more obvious3.In low- and middle-income nations, notably, hypertension is a major contributor to cardiovascular disease and premature death4. According to global research, the number of individuals with all-stage CKD reached almost 700 million in 2017, resulting in 1.2 million deaths5.Besides, hypertension is also the primary risk factor for chronic kidney disease (CKD). Hypertension coexists in approximately 80–85% of CKD and in hypertensive patients, about 15.8% have CKDHowever, CKD can be reversed in the early stage of renal damage. As a result, for a better prognosis, early detection and treatment are crucial.6, reactive oxygen species (ROS) could cause glomerular cell dysfunction, renal vascular endothelial injury, and the production of proteinuria7, by increasing renin release8, stimulating renal afferent nerve activity9, affecting renal arteriole systolic and perfusion pressure10, promoting proinflammatory signaling pathway  and major transcription factors such as activating protein-1 (AP-1) and nuclear factor kappa-B (NF kB)11. Superoxide dismutase (SOD) is one of the most important antioxidants enzymes, which can specifically scavenge intracellular and extracellular superoxide in vivo by decomposing it into hydrogen peroxide and oxygen molecules. Therefore, SOD plays an important role in maintaining the balance of redox. Given the important role of SOD on the balance of redox and renal damage, we are tempted to propose that SOD maybe an independent protective factor for microalbuminuria. Its link with the microalbuminuria of hypertension (HM), however, has yet to be determined. This study was designed to investigate the relation between SOD and HM, hoping to provide a new direction to prevent and treat hypertension with microalbuminuria.According to related research, oxidative stress was the main cause of hypertension with microalbuminuria12. Exclusion criteria: (1) Urinary microalbumin/creatinine ratio (UACR) ≥ 300 mg/g; (2) Patients with secondary hypertension; (3) Patients with diabetes; (4) Renal parenchymal or vascular lesions; (5) Severe cardiac, hepatic and renal failure; (6) Tumor; (7) Cardiovascular and cerebrovascular lesions within 6 months. According to the UACR, 690 patients were classified into the HM group  and hypertension without microalbuminuria group (NHM) . The study was approved by the ethics committee of our hospital, and all patients had given informed consent.A total of 690 patients were included in the study based on their diagnosis of hypertension in Shandong Provincial Qianfoshan Hospital from January 2017 to December 2018. Inclusion criteria: All patients followed the 2018 ESC/ESH hypertension guidelines1-microglobin (ɑ1-MG), urinary microalbumin (mAlb), homocysteine (Hcy), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea (BUN), blood uric acid (UA), serum creatinine (Scr), triglycerides (TG), retinol-binding protein (RBP), estimation of the glomerular filtration rate (eGFR); high-density lipoprotein cholesterol (HDL-c), lipoprotein-cholesterol (LDL-c), total cholesterol (TC), SOD, lipoprotein A (Lpa), blood glucose (GLU) and medication information were collected.General clinical data included gender, age, smoking history, drinking history, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), grade of hypertension, coronary atherosclerotic heart disease (CAD) and laboratory findings included ɑClinic blood pressure was measured three times consecutively at each of the clinic visits using the HEM 7011 BP monitor  after the participants had been seated for at least 5 min. Baseline clinic BP was the average of the six BP readings at the two screening visits.1-MG were detected by ELISA kit . SOD , RBP . Lp(a) , mAlb . UA  were detected. Estimated glomerular filtration rate was calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula13. Urine albumin  and urine creatinine  were measured, and the ratio of albumin to creatinine was calculated. All detection steps and operations were carried out in accordance with the kit instructions.After 12 h. of fasting, blood samples were collected from the anterior cubital vein between 8 a.m. and 10 a.m. Early-morning primary urine was considered to be morning urine. All blood and urine samples were analyzed in the laboratory of the Shandong Provincial Qianfoshan Hospital, their quality was strictly controlled. Detection of TC, LDL-C, TG, HDL-C used the blood lipid determination kit of Beijing Leadman Biochemical Technology Co., LTD, using enzyme-linked immunosorbent test (ELISA) method; SCr and BUN used the renal function biochemical kit of Shanghai Tongjing Life Technology Co., Ltd, to determine BUN by urease-glutamate dehydrogenase method and SCr by oxidase method. Detection of GLU was determined using the hexose kinase method using the glucose determination kit from Beijing Jiehui Bogao Biotech Co., Ltd. Hcy was detected by homocysteine automatic analysis detector, which was measured by Beijing mreda Technology Co., LTD, ALT, AST, ɑX ± S, and an independent sample t-test was used for comparisons between groups. When the data did not conform to a normal distribution, M  was used to express our data and the Mann–Whitney U test was used for comparisons. Categorical data were presented as examples and percentages and examined with 2 test. The association between UACR and SOD was investigated using Spearman correlation analysis. The risk factors of HM were determined by using univariate and multivariate logistic regression. P < 0.05 was considered as a statistically significant difference.Statistical analysis was performed using the Statistical Package for the Social Science (SPSS) version 25.0 . Continuous data with normal distribution were expressed as The studies involving human participants were reviewed and approved by Ethics Committee of Shandong Provincial Qianfoshan Hospital. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.Table 1-MG, mAlb, HCY, BUN, UA, Scr, RBP and GLU were significantly higher than NHM group, while SOD, drinking history and eGFR were significantly lower than NHM group  in the t-test were used as the independent variable, whereas the early renal damage occurred was taken as the dependent variable, establishing a univariate logistic regression model, which showed that the grade of hypertension, SBP, Hcy, Scr, RBP, mAlb, UA, Lpa were risk factors for HM, SOD, drinking history and eGFR were protective factors  to promote vasoconstriction15 and affect the reabsorption of sodium ions, resulting in the imbalance of water and sodium16. SOD is a key antioxidant enzyme in the human body that eliminates superoxide anions' cellular damaging effects17. When compared with the NHM group, the SOD level in the HM group was significantly lower, which was inversely proportional to UACR. Furthermore, we also found that a high level of SOD was an independent protective factor for HM, even after adjustment for other relevant predictors including mAlb, α1-MG and Scr, suggesting that SOD might be a potential therapeutic target for HM in patients with hypertension. Adler18 reported that reduced SOD expression led to increased oxidative stress and the development of CKD in rat animal models of spontaneous hypertension. Furthermore, inhibition of ROS with SOD mimics drug, or genetic deletion of a component of the signaling cascade, usually attenuated or delayed the onset of hypertension and preserved the kidney structure and the function19. By knocking down nuclear respiratory factor-1 (Nrf1), the superoxide production was further reduced, which relieved hypertension and reduced the target organ damage20. The rats without the SOD gene knockout produced considerably less goal-ole ROS than the SOD gene knockout rats as the pressure of renal arteriole perfusion increased21. Besides, SOD gene knockout rats exhibit increased vascular contractility and lowered vascular compliance in the long term, with a higher probability of vascular remodeling. On the other hand, with the decrease of superoxide, the NO reuse rate decreased, which then prevented the formation of cytotoxic proximities22. Interestingly, long-term administration of SOD mimetic drug could attenuate the renal effects of oxidative stress, atrophy, and fibrosis23, suggesting that SOD may be an important antioxidant enzyme that helps to preserve the kidneys by reducing the generation of reactive oxygen species.The kidney is one of the most important target organs of hypertension. Mostly, the renal damage has insidiously early-onset and gradually increases as the disease progressed, which can form hypertensive nephropathy, causing an extremely poor prognosis24. Young25 found that SBP was the most common cause of impaired renal function in older individuals in a large-scale cross-sectional investigation. In a study of 998 older individuals with essential hypertension, Leng26 found that 24-h mean SBP was significantly associated with UACR levels, which was also in accordance with our findings. Plasma RBP is an adipokine, and the main physiological role is to transport retinol to peripheral tissues, mainly excreted through the kidney27. Marczak28 conducted a study of RBP4 and renal function levels, they found that eGFR was the most important factor affecting RBP levels. When renal damage occurred, estimation of the eGFR was reduced, which in turn led to the decrease of RBP volume in renal clearance plasma and the increase of RBP levels in plasma. Interestingly, we found that drinking was a protective factor for microalbuminuria in hypertensive patients. Although the type of drinking was not assessed, this finding may be due to the antioxidant components of alcohol drinks such as wine and beer. Future studies need to clarify the exact role of drinking in the incidence of microalbuminuria.At the same time, SBP and RBP were found to be independent risk factors for hypertension with HM in this study. Elevated SBP can cause renal damage by increasing the oxidative stress response and affecting the myogenic contractile effects in patients with hypertensionOur research does have certain limitations: 1. Because this is a retrospective observational study with no follow-up data, it is impossible to investigate the effect of SOD on patient outcome; 2. Due to the relatively small sample size of this study, further subgroup analysis of different blood pressure grades and liver functions is not possible; 3. This is a single-center study, and the results should be confirmed by multi-center and large samples.To summarize, in hypertensive patients, a substantial, negative correlation between SOD and early renal damage was found, suggesting that SOD may protect renal function. SOD is a common and inexpensive index in clinic and is an important marker of oxidative stress. By analyzing its correlation with early renal damage in hypertension, it might explain the possible mechanism of hypertensive renal damage and provide a new direction for diagnosis and treatment.


Although the use of vasopressors to maintain haemodynamic goals after acute spinal cord injury (SCI) is still recommended, evidence regarding the target values and possible risks of this practice is limited, and data on haemodynamic parameters unaffected by catecholamines are rare. In this pilot study, we show the haemodynamic profile of patients with acute SCI mainly unaffected by vasopressor use and other factors that influence the cardiovascular system.From March 2018 to March 2020, we conducted a prospective, single-centre pilot study of 30 patients with acute SCI. Factors that could affect the cardiocirculatory system other than SCI  led to exclusion. A total of 417 measurements were performed using the PiCCO™ system.1447.23 ± 324.71 dyn*s*cm−5*m2), mean central venous pressure  and mean global end-diastolic volume index  deviated from the reference range, while the mean cardiac index (CI), mean stroke volume index (SVI), mean arterial pressure (MAP), and mean heart rate (HR) were within the reference range, as indicated in the literature. A mixed model analysis showed a significant negative relationship between norepinephrine treatment and MAP , SVRI  and GEDVI .The mean systemic vascular resistance index (SVRI, These findings could lead to an adaptation of the target range for SVRI and MAP in patients with acute SCI and therefore reduce the use of vasopressors. Acute spinal cord injury (SCI) can lead to haemodynamically relevant vasoplegia of the peripheral vessels and bradycardia due to the abrupt loss of sympathetic control and overstimulation of the parasympathetic nervous system. The extent of these symptoms depends on the level of the SCI, with lesions above Th6 being particularly associated with haemodynamic instability . HoweverThere are limited data on cardiocirculatory responses in patients with acute SCI. While a few previous studies assessed haemodynamics using the Swan-Ganz catheter, the results obtained were always biased by vasopressor use and were limited to the first week after SCI , 17. OurThe study was conducted prospectively in a single centre. Written informed consent was obtained from the patients or their legal representatives prior to inclusion. The study was approved by the Ethics Committee of the Ruhr University Bochum (No. 17–6002-BR).All patients treated in the intensive care unit (ICU) of the University Hospital Bergmannsheil Bochum between March 2018 and March 2020 suffering from traumatic SCI with an acute onset of neurological symptoms (< 24 h) and who required regular arterial blood gas analyses or invasive blood pressure monitoring as part of their treatment were eligible for inclusion. The patients underwent neurological examination according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) by the American Spinal Injury Association (ASIA) and the International Spinal Cord Society ), CVP  and GEDVI  specified in the literature . The increase in cardiac output could be explained by an increase in preload. The CVP is used as a marker for preload in the formula for SVRI mentioned above. Since venous pressure can be influenced by many factors and is not recommended on its own for either volume status or fluid responsiveness , we inclIn clinical practice, the aforementioned evidence led to relatively high MAP goals in patients with SCI. However, the resulting use of vasopressors and the consecutive need for invasive monitoring leads to delays in patient mobilization and longer hospitalization .Our data suggest that adjustment of the target values for MAP and SVRI could be justified and could lead to a more focused application as well as reduced dosage of vasopressors. We acknowledge that this study did not assess the neurological outcome of patients and therefore cannot determine whether a more restrictive use of vasopressors for blood pressure management might lead to a worse neurological outcome. However, to our knowledge, there is no evidence that “high normal” blood pressure (MAP 85 mmHg) leads to a better neurological outcome than normotension. Rather, based on our experience with severe cerebral trauma, the spinal perfusion pressure seems to be responsible for a difference in outcome . TherefoFurthermore, the use of the thermodilution-based PiCCO™ system could serve as a safe and easy-to-use means of haemodynamic monitoring in acute SCI. However, the use of thermodilution-based measurements is limited to the ICU and reserved for only those patients who need invasive blood pressure monitoring or regular blood gas analysis as part of intensive care treatment. The indication to maintain or remove a central catheter in the ICU setting, especially in the case of invasive blood pressure monitoring using vasopressors, must be questioned daily. In the author’s view, continuous surveillance of blood pressure in patients with SCI is a key aspect in early mobilization, as it allows for a quick and accurate adaptation of the vasopressor dosage if blood pressure suddenly drops. In the author’s experience, the arterial catheter itself does not delay early mobilization; rather, vasopressor therapy often hinders the physician from initiating mobilization. Especially in patients with acute SCI, blood pressure may vary greatly depending on the patient’s position. Therefore, in our view, invasive monitoring is mandatory in early mobilization.As maintaining central catheters only for research purposes might escalate treatments without any clinical need, we did not specify a period of time for measurements in our study protocol. Therefore, the duration of measurements varies greatly between patients Table . AdditioSome of the haemodynamic measurements were performed while patients were ventilated and/or sedated. As the haemodynamic profiles of a sedated and intubated patient could differ from a fully aware and spontaneously breathing one, ventilation and/or sedation may have biased the measurements. Furthermore, we did not differentiate between the neurological level/location of the SCI.In addition, the number of patients enrolled in the study was very small. With the beginning of the COVID-19 crisis, the number of traumatic SCI cases dropped significantly, and fewer patients than initially anticipated were included. This could reduce the statistical power of our findings.Further studies that examine the haemodynamic profiles of a larger sample of patients after acute SCI are needed for a better understanding of the cardiocirculatory changes caused by SCI. Long-term follow-up and regular assessment of the neurological status of these patients could show whether a certain haemodynamic profile might yield a higher or lower chance of neurological improvement and complications.In a cohort of patients with acute SCI, the systemic vascular resistance index was lower than the reference range. This was observed independent of the use of vasopressors. Cardiocirculatory monitoring using the PiCCO™ system is easy to use and could help define new cardiocirculatory goals in acute SCI.


Introduction: Fluid overload in chronic kidney disease (CKD) is an independent risk factor for all-cause mortality. The volume of ultrafiltrate removed during haemodialysis is usually assessed clinically. Assessment of overhydration by body composition monitor (BCM) using bioimpedance spectroscopy is an objective method. This study was conducted to identify the prevalence of overhydration in CKD patients on maintenance haemodialysis and thereby assess the effects of BCM targeted dry weight attainment.Methods: All patients included in the study were assessed for one month before enrolment for blood pressure, intradialytic events during each dialysis and BP medications. Overhydration was defined as the ratio of overhydration to extracellular water (OH/ECW) > 1.1. Overhydrated patients were brought to BCM targeted dry weight by increasing ultrafiltrate to 500mL/week more than their routine intradialytic weight gain. The effect of attaining BCM target dry weight on blood pressure and intradialytic events were analysed.Results: Out of 110 patients, overhydration was seen in 30 (27.2%); only 20 had clinically evident overhydration. Body composition monitor guided dry weight was achieved in 28 of the 30 patients after a mean duration of 20 weeks. After achieving the target dry weight, there was a significant reduction in intradialytic hypertension events . Surprisingly, there was a reduction in episodes of intradialytic hypotension as well, though this did not reach statistical significance. There was a clinically significant reduction in mean systolic and diastolic blood pressures .Conclusion: The study underlines the importance of BCM-based hydration status assessment and target dry weight attainment in better control of intradialytic events and blood pressure in patients on maintenance haemodialysis. Achieving euvolemic status in patients on maintenance haemodialysis is extremely important. Inadequate fluid removal during dialysis leads to volume overload and chronic hypertension; excessive fluid removal leads to intradialytic hypotension. Both, increase mortality in patients with chronic kidney disease ,2. The dBIS is a simple, inexpensive, and non-invasive method -10. It iThere is very limited data on the usage of this technique in the South Indian population. This study was undertaken to identify overhydration in patients on maintenance haemodialysis using BIS and then to bring the overhydrated patients to their body composition monitor (BCM) targeted dry weight. By doing so, we aimed at finding the effect of the bioimpedance technique on the frequency of intradialytic complications and blood pressure control.This was a prospective observational study done at a tertiary care health centre in South India. The study was approved by the Institutional Ethics Committee (Human Studies), Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry. Subsequent to the approval, adult patients who had been on maintenance haemodialysis for a period of at least three months were enrolled after informed consent. Exclusion criteria were post-renal transplantation status, active malignancy, presence of coronary artery stent or cardiac devices such as implanted cardioverter defibrillators or cardiac pacemakers, presence of metal prostheses, artificial limbs, or extremity amputation, liver failure and pregnancy or lactation.At enrolment baseline data were collected. After enrolment, during a one-month run-in period, blood pressure (BP) changes during dialysis were noted. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were checked during each dialysis session , using automated BP apparatus  in the non-fistula arm. Intradialytic hypotension and hypertension were noted. Intradialytic hypotension was defined as one or more of (1) SBP fall of ≥ 20mm Hg, (2) mean arterial pressure (MAP) fall of ≥ 10mmHg or (3) any fall in BP requires intervention  . IntradiA BCM is a portable multifrequency machine  that determines the hydration status of patients. The machine uses electrodes placed in the non-fistula limb (one electrode above and below the wrist and one electrode above and below the ankle separated by at least 3cm). The BCM device determines whole body impedance at 50 frequencies with very high precision. The frequencies used range from 5 kHz to at least 1,000 MHz Since a range of frequencies is used it is called BIS. From the impedance data, the ECW and TBW volumes are determined. Subsequently, using a physiological body composition model that is based on tissue properties, ECF excess or deficiency is calculated. This is called fluid overload (FO) and is expressed in litres. Normal hydration is defined as −1.1 to 1.1  with values below and above this value defined as under and overhydration respectively .The entire study group was divided into overhydrated and non-overhydrated groups. The overhydrated patients were brought to their BCM target dry weight by slowly increasing the ultrafiltrate at the rate of 500mL/week more than their routine intradialytic weight gain. Patients would be on their regular diet for CKD and reduced water intake plans. Once dry weight, as estimated by the BCM had been attained, they were followed up for one month during which blood pressure, intra-dialytic hypotension and hypertension and the number and dose of antihypertensive drugs were closely monitored.Considering an expected prevalence of overhydration using a BCM to be 60%, with 15% relative precision and 5% level of significance the sample size was calculated as 114. Continuous variables were reported with mean or median and interquartile range (IQR). For categorical variables, the frequency with the percentage was presented. Comparisons of baseline characteristics were carried out using one-way ANOVA, analysis of homogeneity between groups or chi-squared tests for categorical variables. Post dry weight attainment variables were compared with baseline variables using paired t-test. Results were considered significant when p < 0.05.The study was conducted from July 2018 to July 2020. We enrolled 110 patients undergoing maintenance haemodialysis. As per the BCM measurement done at the end of the first month, 30 of the 110 patients were found to be overhydrated. The overhydration index ranged from 1.2 to 6.4.Table As shown in Table This study aimed at finding out the prevalence of overhydration in patients with CKD undergoing maintenance dialysis using a BCM. All patients enrolled in the study were undergoing maintenance haemodialysis for at least three months. This three-month run-in period was considered as those initiated on haemodialysis were more prone to cardiovascular mortality when sudden changes in ultrafiltration were made.All the patients enrolled in the study were dialysed with the volume of ultrafiltrate removal based on the clinically observed dry weight. Twenty out of the 30 patients in the overhydrated group had clinical features of volume overload in the form of either pedal edema, pleural effusion or pulmonary edema. Ten of the 30 patients who were found to have overhydration by a BCM were clinically euvolemic. Hence, ultrafiltrate removal based on clinically calculated dry weight may not be accurate and would result in decreased ultrafiltrate removal resulting in persistent overhydration which is associated with high mortality.The prevalence of overhydration in our study was 27.2%. Wizemann et al. found a prevalence of 21.5% in a study conducted on 269 patients in three centres across Europe. Post HD BCM values were taken to classify patients as overhydrated or non-overhydrated . OnofrieIn our study, there was a decrease in mean SBP and DBP by 5mmHg and 3mmHg, respectively. Machek et al. found a reduction of SBP by 25 mmHg and a 35% reduction in antihypertensive medication use . The majIntradialytic hypertension is a predictor of cardiovascular risk and a marker of mortality in patients on maintenance haemodialysis . Our stuIn this study in spite of ultrafiltrate removal over the interdialytic weight gain, there was a decrease in the number of intradialytic hypotension events, though not clinically significant. The reasons attributable to the decrease in hypotension events could be that once the intravascular volume got corrected, the ultrafiltrate removal rate would have also decreased. Further, as the intravascular volume decreased the preload would decrease resulting in improved cardiac function and thereby a decrease in hypotensive events ,20.The study also brought out the difficulties in the attainment of dry weight. Out of 30 patients in the overhydrated group, most patients reached dry weight over a mean duration of 20 weeks rather than the 12 weeks as planned. One of the patients remained overhydrated for a period of 104 weeks. There was a tendency for increased interdialytic weight gain with increased ultrafiltrate removal early in the study; hence, the subsequent volume of ultrafiltrate removed was restricted to prevent intradialytic complications.LimitationsAdherence to dietary restrictions regarding salt and fluid intake could not be strictly implemented. Left ventricle function which has a bearing on intradialytic events was not assessed for all the patients in the overhydrated group.The study validates the use of BCM in our study population. The study shows a significant decrease in intradialytic hypertension and a non-significant decrease in the mean SBP and DBP, intradialytic hypotension and a decrease in the number of antihypertensive medications for blood pressure control. The decrease in intradialytic hypertension events was due to change in intravascular volume through BCM-adjusted dry weight attainment. Further, large randomized controlled studies are needed to identify the benefits of BCM over clinical methods in target dry weight attainment and their effect on intradialytic complications and control of blood pressure.