Vascular dementia (VaD) is the second most common form of dementia. However, there were mixed evidences about the association between blood pressure (BP) and risk of VaD in midlife and late life and limited evidence on the association between pulse pressure and VaD.This is a population-based observational study. 265,897 individuals with at least one BP measurement between the ages of 60 to 65 years and 211,116 individuals with at least one BP measurement between the ages of 70 to 75 years were extracted from The Health Improvement Network in United Kingdom. Blood pressures were categorized into four groups: normal, prehypertension, stage 1 hypertension, and stage 2 hypertension. Cases of VaD were identified from the recorded clinical diagnoses. Multivariable survival analysis was used to adjust other confounders and competing risk of death. All the analysis were stratified based on antihypertensive drug use status. Multiple imputation was used to fill in missing values.After accounting for the competing risk of death and adjustment for potential confounders, there was an association between higher BP levels in the age 60–65 cohort with the risk of developing VaD  for prehypertension, 1.90  for stage 1 hypertension, and 2.19  for stage 2 hypertension) in the untreated group. There was no statistically significant association between BP levels and VaD in the treated group in the age 60–65 cohort and age 70–75 cohort. Analysis on Pulse Pressure (PP) stratified by blood pressure level showed that PP was not independently associated with VaD.High BP between the ages of 60 to 65 years is a significant risk for VaD in late midlife. Greater efforts should be placed on early diagnosis of hypertension and tight control of BP for hypertensive patients for the prevention of VaD.The online version of this article (10.1186/s12877-017-0649-3) contains supplementary material, which is available to authorized users. Hypertension and dementia are common disorders in the elderly. Among people aged 60 years and over, the prevalence is estimated to be around 5 to 7% for dementia and over 50% for hypertension , 2. VascThe association between BP and dementia may be age dependent, , 7 with Electronic medical records (EMR) contain rich clinical information, in which more than 50% of patients have at least 2 blood pressure measurements . EMR alsThis study was conducted using The Health Improvement Network (THIN) that is one of the largest source of continuous primary care data in United Kingdom (UK). Prospective data collection in THIN started in 2002 with data dating back to the early 1980s. THIN received anonymized patient data from general practice computer systems used for patient management and research purposes. It is a primary care EMR database with the patient information recorded during routine physician visits, such as diagnoses, prescriptions, physiological measurements, diagnostic tests, lifestyle information, and referrals to secondary care. THIN holds anonymized longitudinal medical records for over 11.1 million individuals with more than 3.7 million who remain actively registered. THIN is demographically representative of UK . The ReaWe conducted a retrospective population-based cohort study. Two independent study cohorts were created. The first cohort included individuals with at least one blood pressure measurement between the ages of 60 to 65, and the second cohort included individuals with at least one blood pressure measurement between the ages of 70 and 75. We used the date of last blood pressure measurement within 60 to 65 or 70 to 75 as the index date of follow-up. To ensure an adequate period of follow-up, we only included individuals with an index date between the years 1989 and 2004 and who have registered in THIN for at least 2 years before the index date. All individuals were followed until they experienced the any one of the following: diagnosis of VaD, died, left the THIN database, or the follow-up ended (14 May 2012). Anyone with a diagnosis of VaD before the index date was excluded.We extracted all the blood pressure values measured within 2 years prior to the index date and calculated the average systolic (SBP) and diastolic blood pressure (DBP). BP (measured in mmHg) were classified into 4 categories: normal: SBP < 120 and DBP < 80; prehypertension: 120 ≤ SBP < 140 or 80 ≤ DBP < 90; stage 1 hypertension: 140 ≤ SBP < 160 or 90 ≤ DBP < 100; stage 2 hypertension: SBP ≥ 160 or DBP ≥ 100 according to the criteria of the seventh report of Joint National committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-7) . IndividWe ascertained the cases of VaD using the diagnosis codes E004 - arteriosclerotic dementia/multi-infarct dementia and Eu01 - vascular dementia/arteriosclerotic dementia. The index date of VaD was the earliest diagnosis date recorded in the THIN. Diagnosis information in THIN are generally well recorded and have been successfully used in several studies on dementia , 17. AccIndividuals with the diagnosis of diabetes, stroke, and depression prior to the index date were identified using the Read codes listed in Quality and Outcome Framework- National Health Science (QOF-NHS). History of head injury and Parkinson’s disease was identified based on Read codes found in a text search in the Read code dictionary . All codWe extracted all the antihypertensive drugs information . The mean blood pressure value for each category was calculated. The cumulative incidence of vascular dementia was estimated using the product-limit life-table method, accounting for the competing risk of death . ProportThe variables of smoking status and BMI had missing values. We approached this issue using two different methods. First, models were developed using only the observations without missing values. Second, we used the multiple imputation method to impute ten versions of complete dataset. The multiple imputation allows for the uncertainty about the missing data by creating several different plausible imputed data sets and appropriately combining results obtained from each of them. Models were separately developed for 10 complete datasets and the results were combined for the final inference .The clinical characteristics of both study cohorts are summarized in Table III and IV in the online-only supplements. In total, there were 265,897 patients (65.1% with stage 1 and 2 hypertension) in the age 60–65 cohort and 211,116 patients (76.3% with stage 1 and 2 hypertension) in the age 70–75 cohort. The proportion of patients with at least 2 BP measurements within a 2 year period was 58.4% of in the age 60–65 cohort and 64.4% in the age 70–75 cohort. For the age 60–65 cohort, 46.7% were male and 2.5% and 6.7% had a history of stroke and diabetes, respectively; for the age 70–75 cohort, 43% were male and 2.8 and 7.7% had a history of stroke and diabetes, respectively.We explored the association of systolic and diastolic blood pressure with vascular dementia by estimating the age and sex standardized incidence rate of vascular dementia for each category of SBP and DBP Fig. . There wThe proportion of male patients decreased with higher BP levels (Table III). The proportion of current smokers decreased with higher BP levels while the proportion of individuals with obesity increased. Individuals with normal and stage 2 hypertension have slightly more missing values than the other two groups. The proportion of patients with a history of diabetes, stroke and TIA increased at higher BP levels while the proportion of patients with a history of depression, head injury, and Parkinson’ disease decreased at higher BP levels. Around 15% to 22% of individuals died, with the highest proportion of death for those with stage 2 hypertension. The mean follow up time was 11.0 years (standard deviation (SD): 4.97).Figure The proportion of male patients decreased with higher BP levels, ranging from 55.2 to 37.1% (Table IV). Similar to the late midlife cohort, the proportion of patients with obesity increased at higher BP levels and the proportion of patients with a history of depression, head injury, and Parkinson’s disease decreased at higher BP levels. In contrast to the age 60–65 cohort, the proportion of patients with a history of stroke, TIA, and diabetes decreased at higher BP levels. During follow-up, 32 to 39% of individuals died, with highest proportion of death in those with stage 1 hypertension. The mean follow-up time was 8.84 years (SD: 4.55).Figure In this study, there is an increasing risk of VaD with increasing levels in the age 60–65 cohort without antihypertensive drug, while such an association was not observed in the age 70–75 cohort. Therefore, optimal control of late midlife BP levels and prescription of antihypertensive drugs may be important to reduce the risk of VaD. Further research is still needed to clarify the role of late-life high blood pressure on the prognosis of VaD, especially for patients aged 70 and above.Several studies that have previously examined the association between VaD and midlife BP levels reached similar conclusions. The Hisayama study found that subjects with prehypertension, stage 1, and stage 2 hypertension in midlife around 58 years) had higher risk of VaD after adjusting for potential risk factors 8 years h. PatientTrials of antihypertensive therapy have not yet clarified the impact of blood pressure lowering on vascular dementia. Our study identified the increasing risk of VaD with an increase of BP levels for the individuals without the use of antihypertensive drugs, while there was no association between BP levels and VaD in the treated individuals. A recent meta-analysis of trials and cohort studies showed promising findings that diuretic-based lowering of blood pressure prevents dementia . Other tIncreases of PP in midlife is closely related to the increases of SBP. The associations between PP and VaD were not significant when stratified analyses at each BP level and treatment status were conducted. Therefore, PP was not independently associated with VaD. This is consistent with results from the other study . Pulse pAfter adjusting the competing risk of death and other risk factors, our study found no association between BP levels and risk of vascular dementia in the age 70–75 cohort. This could be due to several reasons. First, there is a graded increase in the risk of stroke with advancing age,  with a dClear association of late midlife high BP and VaD in untreated group supports the need to treat and control BPs for patients with late midlife hypertension. According to health surveys, around half of patients with hypertension do not have their blood pressure under control . In our Our study is a large, population-based cohort study, which enabled us to examine the association of vascular dementia related to late midlife and late life blood pressure. We also accounted for the competing risk of death and adjusted for several important risk factors for dementia. However, several limitations should be noted. First, selection bias might exist since we only included patients who had at least one blood pressure measurement before the ages of 65 and 75. Around 40% of patients in the study cohorts had only a single measurement of blood pressure and this would have led to some degree of misclassification of blood pressure levels. Also, patients with hypertension requiring frequent visits may increase the reporting of dementia. Second, there are potential problems with misclassification or misdiagnosis of vascular dementia. This issue stems from difficulty with the clinical differentiation and classification of dementia subtypes; [In summary, our study indicates that high blood pressure between the ages of 60 and 65 is a significant risk factor for vascular dementia in an untreated late midlife cohort. Given the strength and consistency of this evidence, greater efforts should be made to diagnose hypertension early, and control blood pressure for hypertensive patients in the prevention to better prevent vascular dementia.Additional files 1:List of Read codes (Table S1) and antihypertensive drugs (Table S2), Clinical characteristics of study cohort with the age of 60 to 65 (Table S3) and 70 to 75 (Table S4). (DOCX 36 kb)


Polyunsaturated fatty acids (PUFAs) have important roles in the pathogenesis of cardiovascular diseases. However, the clinical significance of omega-6 PUFAs in acute cardiovascular disease remains unknown.We enrolled 417 consecutive patients with acute cardiovascular disease admitted to the cardiac intensive care unit at Juntendo University Hospital between April 2012 and October 2013. We investigated the association between serum PUFA levels and long-term mortality. Blood samples were collected after an overnight fast, within 24 h of admission. We excluded patients who received eicosapentaenoic acid therapy and those with malignancy, end-stage kidney disease, chronic hepatic disease, and connective tissue disease.p < 0.01). Kaplan–Meier curves showed that survival rates were significantly higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts , although omega-3 PUFAs were not associated with prognosis. Furthermore, in patients with acute decompensated heart failure (ADHF), survival rates were significantly higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts . However, among patients with acute coronary syndrome, none of the PUFA levels were associated with prognosis. Among patients with ADHF, after controlling for confounding variables, DGLA and DGLA/AA were associated with long-term mortality , whereas AA was not associated with prognosis.Overall, 306 patients (mean age: 66.4 ± 15.0 years) were analysed. During the follow-up period of 2.4 ± 1.2 years, 50 patients (16.3%) died. The dihomo-gamma-linolenic acid (DGLA) levels, arachidonic acid (AA) levels, and DGLA/AA ratio were significantly lower in the nonsurvivor group than in the survivor group  contains supplementary material, which is available to authorized users. Polyunsaturated fatty acids (PUFAs) play structural and functional roles as membrane components and precursors for physiologically active substances involved in inflammation . PUFAs aPUFAs, particularly omega-3 PUFAs, have several important roles in the prevention of cardiovascular diseases and have anti-inflammatory and anti-atherogenic effects –14. Prev2], chronic hepatic disease, and connective tissue disease , in which the PUFA hypothesis was generated retrospectively; however, data were collected systematically and prospectively. We enrolled 417 consecutive patients with cardiovascular diseases admitted to the cardiac intensive care unit at Juntendo University Hospital between April 2012 and October 2013. We excluded patients who received EPA therapy and those with malignancy, end-stage kidney disease [defined as an estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 mOverall, 306 patients were analysed in this study. The mean patient age was 66.4 ± 15.0 years. Of the 306 patients, 209 (68.3%) were male. All patients were Japanese. Juntendo University Hospital is located in Tokyo, the capital of Japan, and none of the patients were employed in a primary industry. Based on socio-economic status, the patients included 145 retirees or housewives (47.4%), 130 white-collar workers (42.5%), 6 physical laborers (2.0%), and 5 who received public assistance (1.6%). The occupations of the other 20 patients (6.5%) were unclear from the medical records. The mean follow-up duration was 2.4 ± 1.2 years, and the maximum follow-up duration was 3.7 years.Acute decompensated heart failure (ADHF) was defined according to the diagnostic criteria of the Framingham study . Acute c2) = 194 × creatinine−1.094 × age−0.287  [Whole blood samples were collected after an overnight fast, within 24 h of admission, and were analysed using standardized methods. Tubes for measuring PUFAs contained heparin sodium, those for measuring HbA1c levels contained heparin sodium, ethylenediaminetetraacetic acid disodium salt and sodium fluoride, those for measuring brain natriuretic peptide (BNP) levels contained ethylenediaminetetraacetic acid dipotassium salt, and those for measuring total cholesterol, TG, HDL-C, creatinine, total protein, and albumin contained a fast-acting coagulant. The LDL-C level was calculated using the Friedewald formula. eGFR was calculated based on the Japanese equation that uses serum creatinine level, age, and gender as follows: eGFR (mL/min/1.73 m× 0.739) . Serum ct-test or Mann–Whitney U-test. Categorical variables were analysed using the chi-square test or Fisher’s exact probability test. Correlations between two variables were determined using simple linear regression analysis. The patients were divided into survivor or nonsurvivor groups based on their survival. Unadjusted cumulative event rates for the primary endpoint were estimated using the Kaplan–Meier method and were compared between groups using the log-rank test. We defined cut-offs using the median PUFA levels. We analysed the long-term mortality of patients with ADHF and those with ACS. Among patients with ADHF, univariate and multivariate Cox regression analyses were performed to identify predictors of the primary endpoint. The hazard ratios (HRs) and 95% confidence intervals (CIs) were also calculated. Age, sex, body mass index (BMI), diabetes mellitus, dyslipidemia, hypertension, renal function (eGFR), atrial fibrillation, and cardiac function (left ventricular ejection fraction) were included in the multivariate analyses. JMP12  was used for the statistical analysis, and p-values <0.05 were considered statistically significant.Continuous variables were expressed as means with standard deviations, and categorical variables were expressed as counts and percentages. Comparisons of continuous variables were performed using the Student’s The survivor group included 256 patients (83.7%), and the nonsurvivor group included 50 patients 16.3%). Age and prevalence of atrial fibrillation were significantly higher and BMI, systolic blood pressure, diastolic blood pressure, ejection fraction, and prevalence of dyslipidemia were significantly lower in the nonsurvivor group than in the survivor group. Total cholesterol, LDL-C, TG, and albumin levels were significantly lower, BNP levels were significantly higher, and impaired renal function was more common in the nonsurvivor group than in the survivor group. The administration of diuretics, anticoagulants, and inotropic agents was more common in the nonsurvivor group than in the survivor group (Table 6.3%. Agep < 0.01), although the EPA and DHA levels did not differ between the groups. The DGLA/AA ratio, which indicates the conversion rate of DGLA to AA, was significantly lower in the nonsurvivor group than in the survivor group .As shown in Fig. p < 0.05). AA was negatively related to age, heart rate, and BNP level and positively related to BMI, systolic blood pressure, diastolic blood pressure, and eGFR as well as to total cholesterol, LDL-C, HDL-C, TG, and albumin levels . EPA was negatively related to BNP level and positively related to age, systolic blood pressure, diastolic blood pressure, and ejection fraction as well as to total cholesterol, LDL-C, and HDL-C levels . DHA was negatively related to BNP level and positively related to age, systolic blood pressure, diastolic blood pressure, and ejection fraction as well as to total cholesterol, LDL-C, HDL-C, TG, and albumin levels . DGLA/AA was negatively related to age and BNP level and positively related to BMI and eGFR as well as to total cholesterol, LDL-C, TG, total protein, and albumin levels . EPA/AA was positively related to age, systolic blood pressure, and diastolic blood pressure .In this study population, DGLA was negatively related to age, heart rate, and BNP level and positively related to BMI, systolic blood pressure, diastolic blood pressure, ejection fraction, and eGFR as well as to total cholesterol, LDL-C, HDL-C, TG, total protein, and albumin levels , although the EPA and DHA levels and the EPA/AA ratio were not associated with prognosis . The event-free survival rates were higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts  into two groups based on the median level of each PUFA . The event-free survival rates were higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts , whereas AA, EPA, DHA, and EPA/AA were not associated with long-term mortality  was associated with poor prognosis in patients with ADHF . HoweverOmega-3 PUFA derivatives play a significant role in the process of blood coagulation and inflammation , 35. ManThe present study had several limitations. This study was performed in a single institution, and the study population was small. Moreover, the study duration was short; therefore, it may be difficult to generalize the results. Studies with a larger sample size and longer duration are needed to assess the association between PUFAs and prognosis in patients with cardiovascular diseases.Low serum DGLA levels and a low DGLA/AA ratio predict long-term mortality in patients with acute cardiovascular diseases, particularly those with ADHF, suggesting that low serum levels of omega-6 PUFAs may be a useful predictor and potential therapeutic target in these patients.


Despite advances in medical care, patients who are hospitalized or have spinal cord injuries often develop pressure sores. The objective of this study was to describe the epidemiological characteristics of pressure sores and evaluate factors associated with recurrence and cure. In this historical cohort study, clinical and laboratory data were collected from medical records between 1997 and 2016. Sixty individuals with pressure ulcers were included; mean patient age was 38.1±16.5 (37.0) years, 83.3% were men, and 86.8% identified as white. Most patients (85.1%) had paraplegia, amputation, or trauma of the lower limbs with motor sequelae; the remainder (14.9%) were quadriplegic. Most (78.3%) underwent surgery, and the mean follow-up time was 1.8±2.5 years. The lesions were cured in 25 patients; they recurred in 25% of the patients, and recurrence was seen to be associated with the location of the lesions. Patients with recurrent lesions had more medical consultations and a longer treatment time. Individuals whose ulcers had healed had fewer lesions, higher body mass index (BMI), and a higher proportion of these patients underwent surgery. Level of Evidence IV, Case Series.BMI and location and number of lesions are prognostic factors.  Pressure sores are lesions caused by local ischemia in debilitated patients, who are chronically ill or suffer from spinal cord injury. Friction, moisture and the presence of bony protuberances in contact with support surfaces are risk factors for the development of these sores.Pressure sores have a negative impact on patients’ quality of life and cause a considerable increase in hospital costs. Preventing the development of new lesions and their recurrence after treatment is fundamental to improving quality of life and reducing healthcare expenses.Despite advancements in healthcare, the prevalence of pressure sores remains high, so much that in developing countries, more than 90% of patients with spinal cord injuries have pressure sores.Recurrence rates reach 70% after reconstructive surgeryFew studies have identified clinical and biochemical factors related to the post-treatment prognosis of patients with pressure sores. This study aims to evaluate the clinical and biochemical characteristics of individuals with pressure sores treated at a service that is regarded as a reference in plastic surgery in South Brazil, and to identify the characteristics associated with recurrence after curative treatment.This is a cross-sectional analytical study of adult individuals with pressure sores treated at the plastic surgery outpatient clinic of Polydoro Ernani de São Thiago, a public and tertiary University Hospital of Federal University of Santa Catarina (HU/UFSC) in Florianopolis - Brazil, between 1997 and 2016. Eligible patients were identified from the outpatient and surgical attendance record, and recruited by phone calls or during routine outpatient visits. The individuals or their family members were invited to participate in the study and to sign the informed consent form. Clinical data was extracted from the medical records and biochemical data was obtained from the laboratory registration system. Patients with insufficient registration data in their medical records were excluded.Data on the following clinical and demographic variables were collected: gender, age, race, body mass index (BMI), presence of caretaker, smoking status, alcohol status, comorbidities , dementia, previous stroke, myelomeningocele), disability . The appearance of pressure sores after hospitalization, outpatient nutritional follow-up, and number of medical consultations with the plastic surgery staff were also evaluated. Severity was evaluated according to the location and the number of sores. With regard to treatment, the conduct of reparative surgery and the total time of treatment were documented. Surgical treatment was decided at the discretion of the attending plastic surgeon, and was based on clinical assessment of the patient and the severity of the lesion. The following biochemical variables were analyzed: hemoglobin, leukocyte count, fasting glucose, creatinine, serum sodium and prothrombin activation time (PAT). The test results were expressed in absolute values. The patients were divided into two groups: presence of recurrence, and absence of recurrence with progression to cure. Bivariate analysis was used to compare the groups with regard to each clinical and biochemical characteristic of interest.The mean and standard deviation (SD) of normally distributed numerical variables were compared using the Student’s t-test. The medians of non-normally distributed numerical variables were compared with the Mann-Whitney test. Qualitative variables were expressed in frequencies (%); the Chi-square test or Fischer’s exact test was used to analyze them where required. Values of p<0.05 were considered to be statistically significant. Statistical Package for the Social Sciences, version 17.0  was used to conduct the tests. The statistical program The study protocol met the ethical precepts of the Helsinki Declaration and was approved by the Human Research Ethics Committee of UFSC under the number 1215312.Between 1997 and 2016, 92 patients with pressure sores were identified as eligible for this study. Thirty-two patients were excluded due to incomplete clinical data.In total, 60 patients suffering from pressure sores were included in the study. The average age was 38.1 ± 16.5 (37.0) years, 83.3% were male and 86.8% identified as white. The majority (85.1%) suffered from paraplegia, amputation or trauma of the lower limbs with motor sequelae, 14.9% suffered from quadriplegia, and 10% had myelomeningocele. 3.4% of the patients had had previous stroke, 1.7% had dementia and 1.7% had developed the sores after hospitalization.Among those with paraplegia, 26.5% were victims of stab wounds or firearm injuries, 23.5% were victims of road accidents and 14.7% of falls. Among individuals who suffered amputation or trauma to the lower limbs, 50.0% were victims of road accidents and 50% of falls. Among those with quadriplegia, 25.0% were victims of stab wounds or firearm injuries and 25.0% of road accidents.With regard to the location of the pressure sores, 47.5% were sacral, 37.3% ischial, 8.5% trochanteric, 3.4% calcaneal and 3,4% in other sites. Two or more sores were present in 40.7% of the patients, and the commonest combinations were sacral and trochanteric sores (33.3%), and sacral and ischial sores (29.2%).Most (78.3%) of the patients underwent plastic surgery. The mean follow-up time was 1.8 2.5 years. Twenty-two (36.7%) were lost to follow-up, 10 (16.6%) remain under follow up, 25 (41.7%) were considered cured and 3 have (5.0%) died. Of the 60 patients, 25% have suffered from recurrent lesions at some point during follow-up. The mean time to recurrence after treatment was 0.9 2.6 years.The clinical and biochemical characteristics of the study participants are described in vs. 37.8%; P = 0.005) and longer follow-up . There was a difference in recurrence rate according to the location of the sores (P = 0.037): a higher rate of sores recurred in the sacral region (57.1 vs. 44.4%) and a lower rate in the ischial region (14.3 vs. 44.4%). There was no difference in relation to age, gender, race, BMI, presence of caretaker, smoking status, alcohol status, comorbidities , disabilities , higher mean hemoglobin  and higher rate of undergoing plastic surgery . .  This gro-,,The mean age of the participants in our study is similar to the 29 to 34 years described by Arora et al.-With regard to the location of pressure sores, sacral sores tend to be commonest, varying from 72 to 87% in Hospital São Paulo,,,,-The treatment of pressure sores can be divided into systemic and local options, and the latter can be subdivided into conservative and surgical. Surgical treatment of pressure sores is the therapeutic option of last resort, and is indicated for wounds refractory to clinical treatment or when fast scarring of the lesion is required.With regard to prognostic factors, smoking and comorbidities have been associated with an increased prevalence of pressure sores in patients with spinal cord injury.,bias in their race criterion related to the socioeconomic status of the patients evaluated. The permanence of cure does not depend on adequate surgical treatment in selected patients, but rather on a combination of factors. Multidisciplinary care, focus on the nutritional state of the patient, and use of prophylactic measures are important.Recurrence rates are the main problem in pressure sore reconstructions. Recurrence has been associated to glycated hemoglobin level exceeding 6%, repeating the same flap already used in a surgery that recurred,,,,,We would like to address some limitations to the present study. Considering the prevalence of pressure sores in the general population, the number of patients included in the study is small. However, the University Hospital is a tertiary center for plastic surgery and cares for individuals from the entire state of Santa Catarina, which is one of the smallest states in Brazil. In addition, the study’s sample size is similar to that of other studies on pressure sores.This study enables us to conclude that the commonest cause of pressure sores are spinal cord injuries associated with trauma or congenital diseases, and they are most commonly located in the sacral and ischial regions. The majority of these patients undergo plastic surgery, and the recurrence rates of post-treatment lesions are similar to those found worldwide. Recurrence is associated with the location of the lesions, higher number of medical consultations and longer time of treatment. Cure is associated with higher BMI, higher mean hemoglobin, lower number of sores and plastic surgery treatment.


Subsequently, records from each patient were reviewed over a follow-up duration of at least 3 years. Patients in the LT group experienced worse cardiac function and a higher prevalence of etiology (ischemic vs. no ischemic) and comorbidity (both P < 0.05). In addition, readmission rates of patients in the LT group were higher than that of patients in the NT group (3.32 ± 1.66 VS 1.57 ± 0.89). Overall, deficiencies in FT levels were accompanied with increased mortalities .Testosterone deficiency is present in a certain proportion men with chronic heart failure (CHF). Low testosterone levels in American and European patients with CHF lead to the high mortality and readmission rates. Interestingly, this relationship has not been studied in Chinese patients. To this end, 167 Chinese men with CHF underwent clinical and laboratory evaluations associated with determinations of testosterone levels. Total testosterone (TT) levels and sex hormone-binding globulin were measured by chemiluminescence or immunoassays assays and free testosterone (FT) levels were calculated, Based upon results from these assays, patients were divided into either a low testosterone (LT;  Chronic heart failure (CHF) is a major health problem throughout the world as the final outcome of almost all cardiovascular diseases –11. It iPrevious studies –18 have Baseline characteristics of the 167 Chinese patients with CHF are summarized in Table P < .0001) as shown in the Kaplan-Meier curves for cumulative survival rates of patients in the two groups .At the end of the 3-year follow-up period, there were 47 deaths  with all deaths being cardiovascular. The LT group experienced a significantly higher mortality rate (42/93) as compared to the NT group (5/74) at this 3-year follow-up period . In multivariable models, we included nearly all the variables that were involved in the univariate analyses. The final model included 3 significant independent predictors consisting of LVEF , serum FT , and GFR   and comorbidities .An important component of our current findings is that this androgen deficiency in men with CHF is not only a simple surrogate of disease severity, but also an independent risk factor of prognosis. Data from previous studies have suggested that testosterone insufficiency was associated with an increasing risk of death due to all cardiovascular related diseases in men –28. JankIt is well known that testosterone exerts effects on contractile function of myocardium, vasodilation, insulin resistance, inflammation, coagulation, obesity, endothelial function and alteration in skeletal muscle –35. In aN = 167), aged 36 to 87 years with NYHA functional class II, III or IV (40/66/61), participated in the study. The criteria for study enrollment were as follows: > 6 month symptomatic CHF; left ventricular ejection fraction (LVEF) ≤ 45% as assessed by echocardiogramphy; clinical stability and standard medications for at least 1 month preceding the study; no testosterone replacement or drugs that could affect testosterone levels, such as finasteride, opiates, glucocorticoids and anticonvulsants. In addition, enrollment required that the patients have an absence of heavy alcohol consumption, nephrotic syndrome, liver cirrhosis or cancer history.The study was performed between September 2009 and October 2011 in male Chinese patients hospitalized with CHF in Harbin. Male patients  were measured by chemiluminescence . The inter and intra assay variability coefficients for TT were 2.5% and 5.8%, respectively. Serum levels of SHBG were measured with ELISA , and the inter and intra-assay variability coefficients were 5.2% and 3.0%, respectively. Serum levels of free testosterone (FT) were then calculated using the validated equation of Vermeulen et al. . TestostAll CHF patients underwent clinical and laboratory evaluations, including physical examination, electrocardiogram, echocardiography, chest X-ray, full blood count, serum electrolytes and, if necessary, coronary angiography. Measurements, such as BNP and hemoglobin, were performed by the hospital biochemistry laboratory. Estimated GFR was calculated using the formula from the Modification of Diet in the Renal Disease Study Group.Patients were reviewed regularly, with a follow-up duration extending for at least 3 years. The study investigators were provided with information regarding mortality and readmission rates  directly from patients and their relatives by periodic phone calls, or from the hospital system. No patient was lost to follow-up. The two endpoints included: (1) worsening of heart failure as indicated by readmission and/or (2) cardiac death, defined as death from worsening heart failure or sudden cardiac death.P < 0.05 were considered required for results to be statistically significant. The data analysis was conducted by an independent university-based statistician using SPSS 19.0 .Most variables showed a skewed distribution and were therefore expressed as medians with lower and upper quartiles. Comparisons between the two groups were made using the Mann–Whitney U testor the χ2 test, where appropriate. The association of total and free testosterone levels with all cause of mortality was determined by Cox proportional hazards regression. The following variables were included in the Single-predictor models of the Cox proportional hazard analysis: age, etiology, NYHA class, LVEF, LVEDD, systolic blood pressure, comorbidities, medication, GFR, plasma BNP, hemoglobin and serum levels of TT and FT. During construction of the multivariable models, variables that may be significant predictors of survival according to the Single-predictor models and the clinic, were included in the analyses. These variables included: age, etiology, NYHA class, LVEF, LVEDD, systolic blood pressure, comorbidities, medication, GFR, BNP levels, and serum levels of TT and FT. In order to estimate the effect of serum levels of TT and FT on 3-year survival rates and readmission rates, Kaplan–Meier curves for cumulative survival and readmission rates were constructed for patients in the LT and NT groups. Comparisons of survival rates were tested with the Cox-Mantel log-rank test. Differences with a value of In this sample of Chinese men with CHF, testosterone deficiency served as a predictor for the high rates of 3-year mortality and readmission. Our findings suggested the potential for beneficial effects of testosterone in the treatment of this condition.There remain a number of limitations related to this study. First, the sample size was relatively small. Therefore, these data should be confirmed as based upon a larger sample of patients and preferably contain all NYHA functional classes especially class I. Second, patients enrolled in this study were limited to CHF patients with CHF who had experienced a significant cardiac event requiring hospitalization. Whether these findings would also be applicable to outpatients with stable clinical manifestations should be further investigation. Third, levels of FT and TT were measured at only one time point. It is not known whether FT and TT levels may fluctuate in CHF patients with CHF over the 3-year follow-up period. Nor is it known whether FT and TT levels decreased in NT patients over this 3-year period. Finally, our currents results do not provide any information regarding mechanisms by which testosterone deficiency predicts poor outcome and high readmission rate in men with CHF. Indeed, such mechanisms may involve a multi-factorial process and remains a subject for further investigation.


Sodium-glucose co-transporter 2 (SGLT-2) inhibitors have emerged as a promising drug class for the treatment of diabetic kidney disease. Developed originally as glucose-lowering drugs by enhancing urinary glucose excretion, these drugs also lower many other renal and cardiovascular risk factors such as body weight, blood pressure, albuminuria, and uric acid. Results from the EMPA-REG OUTCOME and CANVAS trials show that these salutary effects translate into a reduction in cardiovascular outcomes and have the potential to delay the progression of kidney function decline. This review summarizes recent studies on the mechanisms and rationale of renoprotective effects.Effects of SGLT-2 inhibitors on the kidney are likely explained by multiple pathways. SGLT-2 inhibitors may improve renal oxygenation and intra-renal inflammation thereby slowing the progression of kidney function decline. Additionally, SGLT-2 inhibitors are associated with a reduction in glomerular hyperfiltration, an effect which is mediated through increased natriuresis and tubuloglomerular feedback and independent of glycemic control. Analogous to diabetic kidney disease, various etiologies of non-diabetic kidney disease are also characterized by single nephron hyperfiltration and elevated albuminuria. This offers the opportunity to reposition SGLT-2 inhibitors from diabetic to non-diabetic kidney disease. Clinical trials are currently ongoing to characterize the efficacy and safety of SGLT-2 inhibitors in patients with diabetic and non-diabetic kidney disease.The glucose-independent hemodynamic mechanisms of SGLT-2 inhibitors provide the possibility to extend the use of SGLT-2 inhibitors to non-diabetic kidney disease. Ongoing dedicated trials have the potential to change clinical practice and outlook of high-risk patients with diabetic (and non-diabetic) kidney disease. The worldwide prevalence of diabetes mellitus will continue to increase in the next decades from 415 million people in 2015 to 642 million in 2040 . ConsequCurrent treatments to prevent or delay kidney (as well as cardiovascular) complications in patients with diabetes focus on lowering blood pressure, HbA1c, body weight, albuminuria, and cholesterol. Targeting these multiple risk factors reduce the risk of cardiovascular disease and kidney function decline , 7. NeveRecently, several strategies have been tested to improve the prognosis of patients with diabetes. One of these strategies was to examine the effects of intensive compared with conventional glucose control on cardiovascular complications. Several large clinical trials in patients with type 2 diabetes showed that aggressive glucose lowering did not result in a reduced risk for macrovascular complications , 9. The The mechanisms for cardiovascular and kidney protection of SGLT-2 inhibitors in patients with diabetes mellitus are incompletely understood. This review summarizes new insights in the potential protective mechanisms of SGLT-2 inhibitors. In the context of recently started renal outcome trials, we will also review the potential benefits of SGLT-2 inhibitors in patients with non-diabetic kidney disease.2 180 gram glucose is filtered each day by the kidney. In these healthy conditions, urinary glucose concentration is absent owing to an effective reabsorption system, consisting of two sodium-glucose co-transporters (SGLT): SGLT-1 and SGLT-2 [18F]fluoro-dapagliflozin . Th. Th69]. An important question to be addressed is of course whether it is safe to use SGLT-2 inhibitors in non-diabetic CKD patients. As described above, the risk of hypoglycemia with SGLT-2 inhibitors in non-diabetic patients is likely low as the degree of glucose-lowering positively correlates with the filtered glucose load which is low in non-diabetic CKD populations. Clinical experience with SGLT-2 inhibitors in non-diabetic conditions is currently limited, but studies in healthy volunteers have shown that SGLT-2 inhibitors can be safely used at high doses, even up to 50-fold the dose used in clinical practice, without inducing hypoglycemia . Thus, tCurrent guidelines recommend to use SGLT-2 inhibitors as adjunct to metformin therapy in patients with type 2 diabetes and established cardiovascular disease . This reVolume depletion is another adverse effect detected in clinical trials. Patients at risk of volume depletion, such as those with gastrointestinal fluid losses or reduced oral intake, are therefore not good candidates to start SGLT-2 inhibitors. In addition, SGLT-2 inhibitors should be withheld during procedures that may reduce renal perfusion such as elective surgery or intravenous contrast procedures in the same way as is done with ACE inhibitors and angiotensin receptor blockers. Along the same line, SGLT-2 inhibitors should not be continued during short-term periods of NSAID use, as the combination of these two drug classes may reduce renal perfusion and may evoke acute kidney injury.The CANVAS program unexpectedly showed that patients treated with canagliflozin had a 2-fold higher risk of lower limb amputations compared with placebo-treated patients. Patients with a history of amputations or with peripheral vascular disease were at highest absolute risk for amputations during the trial, but the relative effect of canagliflozin was similar across subgroups ••. The uSGLT-2 inhibitors are promising. Not only do they improve glycemic control but they also offer substantial protection against progression of cardiovascular and kidney disease in patients with diabetes independent of glucose control. In the last 2 years, several hypotheses emerged that could explain the underlying mechanisms of these protective effects. With respect to the kidney, restoring tubuloglomerular feedback, and attenuating intra-renal hypoxia and inflammation seem plausible mechanisms by which SGLT-2 inhibitors delay the rate of kidney function decline. These glucose-independent effects offer the opportunity to reposition SGLT-2 inhibitors to the non-diabetic CKD population. Ongoing trials will determine whether this novel drug class is indeed an important asset to combat the epidemic of diabetic as well as non-diabetic CKD.


Abdominal obesity is linked to cardiovascular diseases in type 1 diabetes (T1D). The primary aim was to explore associations between abdominal obesity and cardiovascular complications, metabolic and inflammatory factors. The secondary aim was to explore whether achieved recommended treatment targets differed between the obese and non-obese participants.Cross sectional study of 284 T1D patients , consecutively recruited from one secondary care specialist diabetes clinic in Sweden. Anthropometrics, blood pressure, serum-lipids and high-sensitivity C-reactive protein (hs-CRP) were collected and supplemented with data from the patients’ medical records and from the Swedish National Diabetes Registry. Abdominal obesity was defined as waist circumference men/women (meters): ≥1.02/≥0.88. Hs-CRP was divided into low-, moderate-, and high-risk groups for future cardiovascular events . Treatment targets were blood pressure ≤ 130/≤ 80, total cholesterol ≤4.5 mmol/l, LDL: ≤ 2.5 mmol/l, and HbA1c: ≤5 2 mmol/mol (≤ 6.9%). Different explanatory linear, logistic and ordinal regression models were elaborated for the associations, and calibrated and validated for goodness of fit with the data variables.P < 0.001). Women (adjusted odds ratio (AOR) 6.5), cardiovascular complications (AOR 5.7), HbA1c > 70 mmol/mol (> 8.6%) (AOR 2.7), systolic blood pressure (per mm Hg) (AOR 1.05), and triglycerides (per mmol/l) (AOR 1.7), were associated with abdominal obesity. Sub analyses (n = 171), showed that abdominal obesity (AOR 5.3) and triglycerides (per mmol/l) (AOR 2.8) were associated with increasing risk levels of hs-CRP. Treatment targets were obtained for fewer patients with abdominal obesity for HbA1c  and systolic blood pressure . No patients with abdominal obesity reached all treatment targets compared to 8% in patients without abdominal obesity.The prevalence of abdominal obesity was 49/284 (17%), men/women: 8%/29% (Significant associations between abdominal obesity and gender, cardiovascular disease, and the cardiovascular risk factors low-grade inflammation, systolic blood pressure, high HbA1c, and triglycerides, were found in 284 T1D patients. Fewer patients with abdominal obesity reached the treatment targets for HbA1c and systolic blood pressure compared to the non-obese. The intn Sweden .There is evidence that low-density lipoprotein (LDL) is both an indicator of future cardiovascular risk and a causal agent in the atherothrombotic process . Raised Chronic low-grade inflammation has been associated with obesity, insulin resistance, hypertension, hyperglycemia, acute hypoglycemia, dyslipidaemia, cardiovascular disease, and smoking –18. One In line with both international and Swedish national guidelines for diabetes, indications for lipid-lowering drugs at the clinic in 2009 were total cholesterol (TC) > 4.5 mmol/l or LDL > 2.5 mmol/l, in addition to dietary interventions and increased physical activity –23. IndiWe have recently found that alexithymia, which is characterized by impaired capacity to identify and describe feelings, was associated with abdominal obesity . We haveThe primary aim was to explore links between abdominal obesity, metabolic and inflammatory factors and cardiovascular complications in persons with T1D. The secondary goal was to explore whether obtained treatment targets for HbA1c, blood pressure, TC and LDL differed between the obese and non-obese participants.ClinicalTrials.gov: NCT01714986) where “Affect School with Script Analysis” was tried against “Basic Body Awareness Therapy” for persons with diabetes, inadequate glycemic control and psychological symptoms [This study had a cross sectional design and was one of four baseline analyses –27 for asymptoms , 29. Thesymptoms .Fig. 1DeDiabetes specific treatment was divided into three groups: multiple daily insulin injections (MDII), continuous subcutaneous insulin infusion (CSII), and MDII combined with oral antidiabetic agents (OAA) (ATC code A10BA02). The indications for OAA prescription in addition to insulin were obesity and insulin resistance.Anti-hypertensive drugs were calcium antagonists (ATC codes C08CA01–02); angiotensin-converting enzyme (ACE) inhibitors (ATC codes C09AA-BA), angiotensin II antagonists ; selective beta-adrenoreceptor antagonists (ATC code C07AB).Lipid-lowering drugs were HMG CoA-reductase inhibitors (statins) (C10AA).2 for both genders [Waist circumference (WC), weight, length and blood pressure were measured according to standard procedures by a nurse. Abdominal obesity was defined as WC men/women (meters): ≥ 1.02/> 0.88 –32. Gene genders .HbA1c and serum lipids analyses were performed at the department of Clinical Chemistry, Växjö Central Hospital.Venous HbA1c was analyzed with high pressure liquid chromatography, HPLC - variant II, Turbo analyzer . HbA1c > 70 mmol/mol (> 8.6%) corresponds to the 75th percentile in the whole population sample .After an overnight fast, blood samples were collected and serum-lipids were were measured directly , using tSamples for hs-CRP were collected, centrifuged, and stored at − 70 C Celsius until analyzed with spectrophotometry on a Roche Cobas C501 at the diabetes laboratory, Lund University Hospital, Lund. Hs-CRP was 0.54 ± 0.02 mg/l in healthy subjects according to previous research . Hs-CRP The treatment targets recommend by the Swedish National Board of Health and Welfare were for T1D patients: 1) glycemic control: HbA1c ≤52 mmol/mol; 2) systolic/diastolic blood pressure: ≤130/≤80 mmHg; 3) serum-lipids: TC ≤4.5 and LDL ≤2.5 mmol/l .A severe hypoglycemia episode was defined as needing help from another person. Episodes during the last 6 months prior to recruitment were registered.Smokers were defined as having smoked any amount of tobacco during the last year.Physical inactivity was defined as moderate activities, such as 30 min of walking, less than once a week.Cardiovascular complications were defined as ischemic heart disease or stroke/TIA.1, q3; range), and analyses were performed with Mann-Whitney U test. Fisher’s exact test (two-tailed) and Linear-by-Linear Association (two-tailed) were used to analyze categorical data. Crude odds ratios (CORs) were calculated, variables with P ≤ 0.10, and age independent of P-value, were entered in multiple logistic regression analyses . The Hosmer and Lemeshow test for goodness-of-fit and Nagelkerke R2 were used to evaluate each multiple logistic regression analysis model. Ordinal regression analysis (stepwise forward) was performed with 3 risk levels of hs-CRP as dependent variables. Variables with P-values ≤0.10 in simple linear regression analyses were entered into multiple linear regression analyses (Backward). Confidence intervals (CIs) of 95% were used. P < 0.05 was considered statistically significant. SPSS® version 18  was used for statistical analyses.Analysis of data distribution using histograms revealed that age, diabetes duration, hs-CRP, triglycerides, BMI and WC were not normally distributed. Data were presented as median values (quartile (q)n = 284, age 18–59 years, men 56%), persons with abdominal obesity (n = 49) were compared with non-obese persons (n = 235). Baseline data including comparisons between men and women are presented in Table P < 0.001) and general obesity . The men had higher systolic and diastolic blood pressure (both P < 0.001) and lower HDL (P = 0.002). The percentage that reached the recommended treatment targets were for HbA1c: 19%; TC: 48%; LDL: 36%; systolic blood pressure: 65%; diastolic blood pressure: 95%. Only 7% reached all treatment targets.In this population based cross sectional study of persons with T1D (P < 0.001), lipid-lowering drugs (P = 0.012) and cardiovascular complications (P = 0.016); and had higher median values of hs- CRP (P < 0.001), triglycerides (P < 0.001), systolic blood pressure (P = 0.004), LDL (P = 0.021) and TC (P = 0.047). Fewer patients with abdominal obesity compared to the non-obese reached the recommended treatment targets for HbA1c  and systolic blood pressure . No patients with abdominal obesity reached all risk factor treatment targets for blood pressure, TC, LDL and HbA1c compared to 8% in the non-obese.Results of comparisons between 49 persons with abdominal obesity and 235 persons without abdominal obesity are presented in Table P < 0.001), and cardiovascular complications (P = 0.018) (Table P = 0.014), higher prevalence of cardiovascular complications (P = 0.007), and lower prevalence of high LDL (P = 0.006) than non-users of lipid-lowering drugs  6.5), systolic blood pressure (per mm Hg) (AOR 1.05), HbA1c > 70 mmol/mol (> 8.6%) (AOR 2.7), triglycerides (per mmol/l) (AOR 1.7), and cardiovascular complications (AOR 5.7) were associated with abdominal obesity Table . Gender Abdominal obesity (AOR (CI) 5.3 (2.1–13.6)) and triglycerides (per mmol/l) (AOR (CI) 2.82 1.68–4.93)) were associated with increasing risk levels of hs-CRP (Table .93) wereP < 0.001; and HDL (per mmol/l) AOR 6.1 (2.7–13.6), P < 0.001. Negative associations with women were found for diastolic blood pressure (per mm Hg) AOR 0.91 (0.87–0.95), P < 0.001; and age (per year) AOR 0.97 (0.94–0.99), P = 0.005. Systolic blood pressure, TC and anti-hypertensive drugs were not associated with women . Nagelkerke R Square: 0.277. Hosmer and Lemeshow Test: 0.034.Positive associations with women were found for abdominal obesity AOR 8.6 (3.9–19.0), P = 0.004; triglycerides (per mmol/l) AOR 1.7 (1.1–2.5), P = 0.010; and for diastolic blood pressure (per mm Hg) AOR 1.04 (1.00–1.08), P = 0.090. HDL, TC, age, physical inactivity, and LDL were not associated with HbA1c > 70 mmol/mol . Nagelkerke R Square: 0.137. Hosmer and Lemeshow Test: 0.782.The associations with HbA1c > 70 mmol/mol (> 8.6%) were for abdominal obesity AOR 2.7 (1.4–5.4), P < 0.001; anti-hypertensive drugs 6.5 (3.9–9.2), P < 0.001; triglycerides (per mmol/l) 2.0 (0.4–3.6), P = 0.014; men 4.0 (1.6–6.4), P = 0.001; and for abdominal obesity 4.0 (0.8–7.3), P = 0.014. Lipid-lowering drugs (P = 0.73) and diabetes duration (P = 0.99) were not associated with systolic blood pressure. Adjusted R Square 0.276, P < 0.001.The B-coefficients for the associations with systolic blood pressure were for age 0.24 (0.13–0.34), P = 0.006; abdominal obesity AOR 5.5 (1.4–22.0), P = 0.017; and for LDL (per mmol/l) AOR 0.3 (0.1–1.1), P = 0.071. Lipid-lowering drugs, anti-hypertensive drugs and diabetes duration were not associated with cardiovascular complications . Nagelkerke R Square: 0.309. Hosmer and Lemeshow Test: 0.978.Associations with cardiovascular complications were for age (per year) AOR 1.18 (1.05–1.32), P = 0.024). Otherwise, they did not differ by medians for age (P = 0.10), diabetes duration (P = 0.52), diastolic blood pressure (P = 0.52), systolic blood pressure (P = 0.66), HDL (P = 0.49), LDL (P = 0.50), triglycerides (P = 0.70), TC (P = 0.79); or by prevalence of anti-hypertensive drugs (P = 0.124), physical inactivity (P = 0.33), severe hypoglycemia episodes (P = 0.38), HbA1c > 70 mmol/mol (P = 0.48), lipid-lowering drugs (P = 0.72), cardiovascular complications (P = 0.74), or smoking (P = 0.84).The prevalence of abdominal obesity was lower in the 171 patients with hs-CRP measurements than in the patients without hs-CRP measurements , and triglycerides were independently associated with abdominal obesity. Inadequate glycemic control, systolic blood pressure, increasing risk levels of hs-CRP, were in addition to abdominal obesity, also associated with triglycerides. Less patients with abdominal obesity reached the treatment targets recommended by the Swedish National Board of Health and Welfare for glycemic control (HbA1c ≤ 52 mmol/mol) and systolic blood pressure (≤ 130 mmHg), and no patients with abdominal obesity reached all treatment targets for TC, LDL, and blood pressure .Strengths of our study are first that the population of patients with T1D was well-defined, since persons with severe comorbidities and severe substance abuse were excluded. Second, hs-CRP levels above 10 mg/l were excluded, and the CRP values were divided into 3 groups with low-, moderate- or high-risk for future cardiovascular events, as have been recommended in previous research . Also, wThe main limitation of our study was the rather small number of obese persons, particularly when gender sub analyses were performed. There are several possible type 2 errors. The association between the use of lipid-lowering drugs and abdominal obesity did not reach significance. The prevalence of both lipid-lowering drugs and anti-hypertensive drugs in patients with cardiovascular complications was high, but the associations were not significant. Second, the number of hs-CRP values measurements was limited, as we decided not to include hs-CRP measurements stored for more than 1 year. Despite the limited number of hs-CRP measurements and the lower prevalence of obesity in persons with hs-CRP measurements, the moderate and high-risk-levels of hs-CRP were strongly associated with abdominal obesity and triglyceride levels.We have previously shown an association between alexithymia and abdominal obesity in this sample of patients with T1D . In thisAnother gender difference noted was that the men had higher blood pressure than the women, which is in accordance with previous research . The preDue to the described detrimental effects of obesity in T1D, it is necessary to try new ways to both prevent and treat obesity. Reports of beneficial effects on weight and HbA1c have been reported for sodium-glucose cotransporter (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) analogues . StructuSignificant associations between abdominal obesity and both cardiovascular disease and cardiovascular risk factors were found in 284 patients with T1D. Low-grade inflammation, increased systolic blood pressure, inadequate glycemic control, and increased triglycerides were linked with abdominal obesity. The obesity prevalence was particularly high in women. Action against obesity is urgent to prevent cardiovascular complications in patients withT1D.


Solubility of Tumorigenicity 2 (sST2) is a novel biomarker that better stratifies risk of cardiovascular events (CVE) compared to cardiac troponin T(cTnT) in heart failure. We assessed the association of sST2 with the composite outcome of CVE and/or mortality compared to cTnT in kidney transplant candidates.200 kidney transplant candidates between 2010 and 2013 were included. Elevated sST2 was defined as ≥30ng/ml, cTnT≥0.01 ng/ml.Median age 53 (interquartile range (IQR) 42–61) years, 59.7% male and 82.0% white. 33.5% had history of CVE, 42.5% left ventricular hypertrophy (LVH) and 15.6% positive cardiac stress test. Elevated sST2 correlated with male gender, history of prior-transplants, CVE, positive stress test, LVH, elevated cTnT, anemia, hyperphosphatemia, increased CRP and non-transplanted status. Male gender, history of CVE and LVH were independent determinants of sST2. During 28 months (IQR 25.3–30), 7.5% died, 13.0% developed CVE and 19.0% developed the composite outcome. Elevated sST2 was associated with the composite outcome  on univariate analysis but not after adjusting for age, diabetes and cTnT (p = 0.068). sST2 did not change the risk prediction model for composite outcome after including age, diabetes, prior history of CVE and elevated cTnT.Increased sST2 level is significantly associated with variables associated with CVE in kidney transplant candidates. sST2 was associated with increased risk of the composite outcome of CVE and/or death but not independent of cTnT. Larger studies are needed to confirm these findings and determine whether sST2 has added value in CV risk stratification in this cohort of patients. Assessment of cardiovascular risk (CV) in patients with advanced chronic kidney disease (CKD) presenting for kidney transplantation is an important component of every transplant evaluation; however the approach to CV assessment is largely transplant center specific. Besides a detailed history and physical examination, most centers include cardiac testing such as a structural evaluation, typically by echocardiography or coronary angiography and/or a functional assessment such as stress treadmill testing or myocardial perfusion imaging. Several biomarkers including N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), high sensitivity C-reactive protein (hs-CRP) and cardiac troponin T (cTnT) have been studied and shown to correlate with adverse CV outcomes in the end-stage renal disease (ESRD) population–5. Our gSuppression of tumorigenicity 2 (ST2) is a novel biomarker of CV risk currently utilized for risk stratification and prognostication in patients with heart failure  as it prThe Mayo Clinic Institutional Review Board approved this study. Informed consent was waived. Outpatient adult patients with advanced CKD who presented for kidney transplant evaluation at Mayo Clinic, Rochester, MN between May 2010 and November 2013 were included. Patients with history of collagen vascular disease, rheumatoid arthritis, pulmonary fibrosis, chronic obstructive pulmonary disease and clinically significant asthma were excluded as levels of sST2 are known to be increased in these cohorts of patients.th generation Roche Diagnostics assay and it was analyzed as a continuous variable and binary variable with an elevated cTnT defined as a value greater than or equal to 0.01 ng/ml which is the level above the point of detection. High sensitivity CRP was analyzed using the Roche assay and results were reported as low as <0.2 and levels above 2mg/L were considered abnormal. Serum albumin was also analyzed using Roche and HemoCue analyzer was used for hemoglobin.Stored serum samples from all kidney transplant candidates between May 2010 and November 2013 were retrieved. Only samples with at least 75 microliters available for sST2 testing were included. sST2 was analyzed using a high-sensitivity sandwich immunoassay . All samples with an elevated level were diluted to provide quantitative results. In patients with heart failure, the upper reference limit for sST2 is 35 nanograms per milliliter (ng/ml) . In thisClinical characteristics were determined from the medical record including age, sex, race, height, weight, cause of CKD, diabetes status, number of prior transplants, dialysis, history of CV events, transplant committee decision and date of transplantation. Laboratory data abstracted at the time of the transplant evaluation included the following: serum levels of hemoglobin, albumin, uric acid, phosphorus, parathyroid hormone (PTH), creatinine, CRP and cTnT.2 in men or LVMI greater than 89 g/m2 in women), left ventricular ejection fraction, and cardiac stress test findings. Cardiovascular events (CVE) were defined as: a history of acute myocardial infarction or coronary artery revascularization , history of hospitalization for heart failure, peripheral vascular disease defined as surgical or percutaneous lower extremity revascularization or limb amputation, central vascular disease including abdominal aortic aneurysm requiring surgical repair, carotid or renal artery stenosis requiring surgical or percutaneous intervention and cerebrovascular events defined as any ischemic or hemorrhagic cerebrovascular accident. These definitions applied for both pre and post-transplant CVE.Cardiovascular disease assessment variables abstracted from chart review included echocardiogram findings of left ventricular hypertrophy (defined as left ventricular mass index (LVMI) greater than 103 g/mDescriptive statistics such as number of observations, mean, median, standard deviation, and range were provided for quantitative variables, and qualitative or categorical variables were summarized using counts and percentages. Continuous data were reported as median with interquartile ranges (IQR). Wilcoxon Rank Sum test was used for comparison of continuous variables. Comparisons between more than two groups of data were performed by ANOVA for normally distributed and by Kruskall-Wallis test for skewed data. Proportions were compared by Chi-square. Survival analysis was performed using Cox proportional hazard models. Variables significantly associated with the composite outcome were identified by univariate analysis in which each variable was entered separately in the cox hazard model to determine its significance. Variables that were significantly correlated with each other were not entered in the final model together. The final multivariate cox hazard model was performed by entering all the significant variables at the same time. The significance level of the p-value was set at less than 0.05. All statistical analyses were performed using JMP, version 9 . The outcome of interest was the composite outcome of patient mortality and/or CVE. Follow-up was censored at the time of transplant or last follow-up or October 2015.Five hundred and seventy four patients evaluated at the transplant center from May 2010 to November 2013 had stored serum samples available for analysis, of whom 368 were excluded due to inadequate serum sample volume and 6 were excluded because of preserved kidney function as shown in Two hundred kidney transplant candidates were included in the study. This patient cohort was predominately white, male presenting for first kidney transplant evaluation as shown in .The median sST2 in this cohort was 27.8 ng/ml (IQR 19.3–37.8), and 85 (42.5%) patients had an sST2 level ≥30ng/ml. The presence of an elevated sST2 level varied by the underlying cause of CKD. Patients with hypertension or renovascular etiology and patients with failed renal allograft were more likely to have an elevated sST2 level compared to patients with advanced CKD due to polycystic kidney disease or diabetes (p<0.001) Next we evaluated clinical and laboratory variables associated with an elevated sST2 level. Patients with an elevated sST2 were more likely to be male and have a history of failed kidney transplant as shown in Median cTnT level was 0.02 ng/ml (IQR 0.005–0.05). One hundred and thirteen (56.5%) patients had an elevated cTnT level, of whom sixty one (54.0%) had an sST2≥ 30ng/ml. The following variables were associated with an elevated cTnT level: male gender , p = 0.001), diabetes , p<0.0001), dialysis , p<0.0001), prior history of CVE , p<0.0001), presence of LVH , p<0.0001), positive cardiac stress test , p = 0.006) and hyperphosphatemia , p = 0.01).Twenty-four patients of 154 (15.6%) had a stress echocardiogram positive for ischemia at the time of transplant evaluation. Twenty-one (87.5%) patients with positive test for ischemia had an elevated cTnT (p = 0.003) while 15 (62.5%) had an elevated sST2. Ten patients (41.7%) with positive stress echocardiogram required coronary angioplasty or coronary bypass surgery for severe coronary artery disease (CAD). Positive cardiac stress testing and an elevated cTnT were independent predictors of severe CAD requiring intervention [positive stress test: OR 3.38 , p = 0.012, and cTnT: OR 2.98 , p = 0.032). An elevated sST2 was not significantly associated with severe CAD requiring intervention independent of positive stress test and an elevated cTnT.Over a median follow-up of 28 months (IQR 25.3–30), 15 (7.5%) died and 26 (13.0%) suffered CV events. Thirty eight (19.0%) suffered from the composite outcome of death and/or CV event. Twenty nine of the 38 patients (76.3%) suffered from the composite outcome while on the waitlist.Table 4), several variables related to the composite endpoint including older age , p = 0.0118), diabetes , p = 0.0004), increased cTnT level , p = 0.0001), increased sST2 level , p = 0.029), prior history of CV events , p<0.0001), positive stress echocardiogram , p = 0.005), and an ejection fraction below 45% (HR 4.66 (1.57–11.1), p = 0.008). Neither serum creatinine , p = 0.37) nor CRP , p = 0.95) was significantly associated with the composite outcome. On multivariate proportional hazard modeling we assessed the variables that were significantly associated with the composite outcome using two models. Model 1included age, diabetes and log cTnT levels. Model 2 included age, diabetes and log sST2 levels. In model 1, long transformed cTnT was significantly associated with the composite outcome after adjusting for age and diabetes. In model 2, sST2 was not a significant predictor of the composite outcome independent of age and diabetes. Therefore, only older age, increased level of cTnT and diabetes were independently associated with mortality and/or CV event during the follow-up time. An sST2 level ≥30ng/ml was not significantly associated with the composite outcome in univariate (HR 1.64 (0.86–3.17) or multivariate (HR 1.77 (0.92–3.48), p = 0.09) analysis. The relationship of an elevated cTnT with the composite outcome remained significant when cTnT was analyzed as a binary variable (≥0.01ng/ml) in univariate (HR 3.18 (1.48–7.86), p = 0.002) and multivariate (HR 2.23 (1.02–5.62), p = 0.045) analysis. In our cohort, event-free survival was not associated with gender or dialysis.By univariate cox analysis . The findings of this study show that an elevated sST2 correlated with variables predictive of CV events and mortality. Compared to cTnT, sST2 was not an independent predictor of the composite outcome and did not have an added incremental value to the risk prediction model based on clinical risk factors and cTnT.Suppression of tumorigenicity 2 (ST2) belongs to the interleukin-1 receptor family with transmembrane (ST2L) and soluble (sST2) isoforms and functions as a danger signal in response to tissue damage, necrosis and death . The solIt is worth noting that high sensitivity cTnT (hs cTnT) assay was not available at the time of this study. It has been shown that hs cTnT is elevated in 81% of patients with CKD not yet on dialysis and that elevations in hs cTnT are associated with adverse CV endpoints , 28. As On univariate analysis, elevated sST2 was significantly associated with reduced event-free survival , p = 0.029), however this relationship was not independent of other known predictors of CV events and mortality such as older age, diabetes and an elevated cTnT. These findings may be explained by the following: first the median level of sST2 in this cohort was much lower than what has been reported in heart failure patients where sST2 cut-off of ≥35ng/ml is considered abnormal and a level >65ng/ml has the highest sensitivity and specificity in predicting mortality. In our cohort, the median sST2 level was 27.8 ng/ml, much lower than what has been reported in heart failure patients. Second, the association of sST2 with adverse outcome was significant when sST2 was analyzed as a continuous variable but not as a binary variable defined as ≥30ng/ml on univariate analysis. Third, sST2 was not affected by dialysis or diabetes, two important CV risk factors in this cohort, yet it was influenced by prior history of kidney transplants suggesting that sST2 may represent different pathophysiologic mechanisms in CKD.There are several strengths of our study. To our knowledge, this is the first study of sST2 in a cohort of patients with advanced CKD uniformly evaluated for kidney transplant. The availability of pertinent clinical and laboratory variables including cTnT and hs-CRP allowed for a comprehensive analysis of sST2 determinants and follow-up extended to over two years from the day of evaluation. There are also several limitations that warrant discussion. First, because of the small sample size and the small number of events, a type II error cannot be excluded. Moreover, our patient cohort may not be representative of other cohorts of patients being evaluated for kidney transplant as only 60% required dialysis at the time of evaluation and the majority were white. Data on NT-proBNP was not available for comparison as it is not routinely performed as a standard test for patients in the outpatient setting during kidney transplant evaluation at our center. Lastly, data regarding timing of the blood draw with respect to dialysis is not known. This may impact the cTnT data as cTnT levels have been shown to increase after hemodialysis . HoweverThis study shows that in patients with advanced CKD evaluated for kidney transplant, sST2 is associated with several known CV risk factors. However the association of sST2 with increased risk of CV events and/ or mortality was not independent of older age, diabetes and an elevated cTnT level. Further studies are required to establish a reference range of significance in advanced CKD patients and better characterize the association of sST2 with CV outcomes.S1 Data(PDF)Click here for additional data file.


Intradialytic hypotension (IDH) is one of the major problems in performing safe hemodialysis (HD). As blood volume depletion by fluid removal is a major cause of hypotension, careful regulation of blood volume change is fundamental. This study examined the effect of intermittent back-filtrate infusion hemodiafiltration (I-HDF), which modifies infusion and ultrafiltration pattern.Purified on-line quality dialysate was intermittently infused by back filtration through the dialysis membrane with a programmed dialysis machine. A bolus of 200 ml of dialysate was infused at 30 min intervals. The volume infused was offset by increasing the fluid removal over the next 30 min by an equivalent amount. Seventy-seven hypotension-prone patients with over 20-mmHg reduction of systolic blood pressure during dialysis or intervention-requirement of more than once a week were included in the crossover study of 4 weeks duration for each modality. In a total of 1632 sessions, the frequency of interventions, the blood pressure, and the pulse rate were documented.During I-HDF, interventions for symptomatic hypotension were reduced significantly from 4.5 to 3.0  and intradialytic systolic blood pressure was 4 mmHg higher on average. The heart rate was lower during I-HDF than HD in the later session. Older patients and those with greater interdialytic weight gain responded to I-HDF.I-HDF could reduce interventions for IDH. It is accompanied with the increased intradialytic blood pressure and the less tachycardia, suggesting less sympathetic stimulation occurs. Thus, I-HDF could be beneficial for some hypotension-prone patients.000013816. Intradialytic hypotension (IDH) requires immediate medical intervention and/or nursing care. In addition, IDH may reduce the efficacy of dialysis, considerably increase a patient’s discomforts such as consciousness loss, and finally lead to cardiac dysfunction with myocardial stunning –3. ConseOne successful countermeasure is the plasma sodium biofeedback system, which can reduce the burden of IDH . Fluid mThe study was designed as an open, non-controlled, prospective, crossover, multicenter trial. Eight dialysis units in Japan  participated in the study. Approval from ethics committee of Hiro Clinic Oomori, Tokyo, was obtained on 22 April, 2014 , and the study was registered to UMIN (000013816).IDH is defined in this study as systolic blood pressure falling over 20 mmHg from baseline, or presentation of symptoms associated with hypotension requiring any medical interventions, including nursing care , 9. Thes2 or greater than 2.2 m2; or (e) they were on beta-2 microglobulin adsorptive columns.Patients who experienced these IDH complications at least once a week were included in the study. The observation period before entry was 2 weeks, in which inclusion or exclusion was determined. All patients who took part in gave written informed consent. Eligible patients were stage 5 CKD, treated by hemodialysis thrice weekly. Dry weight was clinically and comprehensively determined based on previous history and symptoms such as dyspnea, peripheral edema and blood pressure, to the weight at which patient would remain normotensive. In all participating facilities, chest X-ray was regularly examined to measure cardio-thoracic ratio, which might help to consider appropriateness of dry weight. Patients were excluded if: (a) they had had a cardiovascular event within the past 3 months; (b) they had active inflammatory disease or malignancy; (c) they had systolic blood pressure exceeding 150 mmHg during dialysis; (d) they were treated with a dialysis membrane with a surface area less than 0.8 m® or the TR-3300M® . To ensure patients safety during I-HDF the dialysate purity of the on-line fluid must be guaranteed by multiple endotoxin-retentive filters, and the entire system should be validated by manufacturers to limit endotoxins to below the applicable clinical detection limit and bacteria to less than 10 to minus 6 quality. In this study, hemodiafilter used for I-HDF period was specified to polysulfone TDF-M® , and the membrane area was adjusted to limit any difference less than 0.1 m2 from the subject’s prior dialyzer.I-HDF is a convective type of therapy which is approved by Japanese health care regulations and the reimbursement agency as a modified type of hemodiafiltration. Although the convective volume chosen for this study was too small to meet the definition set forth by the EUDIAL group , the stuAs an example, in patients with 4-h sessions, each infusion bolus was 200 mL and seven infusions were given per session, providing a total of 1400 mL/session according to the protocol , and Wilcoxon singed-rank test, where appropriate. Multivariate logistic regressions were applied to examine predictors for patients who responded to I-HDF.Results were presented as mean ± SD, median and interquartile range or IQR: 25th, 75th percentile, depending on variable distributions, and as percent for categorical variables. Analyses were conducted by Chi-squared test, Student’s http://www.R-project.org/).All of the analyses were conducted using R version 3.1.2 software for statistical computing  and shorter session time . Other demographics were not different.The details of dropouts are summarized in Table Baseline demographics and dialysis parameters of patients in the final analysis are summarized in Table P = 0.003, see Fig. Table P = 0.021). Intradialytic SBP obtained 5 min after infusion increased by 4 mmHg in average . Membrane area and material were significantly different, but this was due to protocol compliance.Along with this, hypotensive sessions also reduced from 337 in HD to 298 in I-HDF (P = 0.041).The data were reanalyzed finally with inclusion of data from the six patients who dropped out during the I-HDF period after assigning these subjects the median intervention score of the worsened subjects. In this final analysis the reduction in intervention frequency remained significant (n = 34), and the patients with the same or increased frequency as non-responders (n = 34) .In univariate comparative analysis, intradialytic SBP rise during HD was 6 mmHg greater in responders. The decrease in interventions thus was paralleled by the observation of greater blood pressure elevation. The treatment time, IDWG and the pressor agent prescription were significantly different between the groups. The corrected UFR was unexpectedly greater in responders. Although not significant, age was suspected to have any effect  study patients . The corA weakness of this study is its relatively small sample size. Although the results obtained are statistically significant, it is necessary to establish that I-HDF really improves comorbidity and survival in a greater number of patients. Further technical improvement is required, such as eventual incorporation of a biofeedback system , 19, andIn studies involving the treatment of sick people, a substantial dropout rate can be anticipated. There were nine dropouts (11 %) in this study, but we eventually included six who stopped during I-HDF as worsened cases, irrespective of the reason the individual dropped out. However, we must be cautious in interpreting the clinical results when dropouts are present in a crossover study.A strength of the study is that the observed reduction in intervention correlates with the observation of increased blood pressure during treatment. It gives validity to the results and supports the usefulness of I-HDF as a countermeasure to IDH. The hemodiafilter membrane material was also matched during I-HDF (polysulfone). This should exclude the possibility that our results were influenced by membrane differences that occurred during I-HDF.Extrapolating from the results of this multicenter study, we may hypothesize that modifying the infusion rate and infusion frequency during treatment of hypotension-prone patients, especially in the case of seniors (around 69 years) with modest ultrafiltration volume  may yield further benefits. Finally, I-HDF is economical because it requires no medications.I-HDF could be a measure to reduce the need for medical intervention and nursing care in some patients with IDH, and associated with raising intradialytic systolic blood pressure while decreasing sympathetic stimulation. The results imply that the current practice of ultrafiltration during dialysis still needs refinement.


The settings of mechanical ventilation, like tidal volume (VT), occasionally need to be adjusted in the process of anesthesia for some special reasons. The aim of this study was therefore to assess the relationship between pulse pressure variations (PPVs) in different settings of VT in anesthetized healthy patients under mechanical ventilation.2) maintained between 30 mmHg and 40 mmHg by changing Respiratory Rate (RR) before incision.Sixty nine ASA I-II patients scheduled for gastrointestinal surgery under general anesthesia were included in this prospective study. All the patients were ventilated at a VT of 6, 8 or 10 ml/kg (predicted body weight) with no positive end expiratory pressure (PEEP) in a random order after intubation. PPV, mean arterial blood pressure, and other hemodynamic and respiratory parameters were recorded in each VT setting respectively after Partial Pressure of End-Tidal Expiration Carbon Dioxide .The values of PPV at different settings of VT showed a tight correlation between each other  can deduce that in any other 2 settings. Further studies are needed to explore the effect of intraoperative confounders for this knowledge to be clinically applied.NCT01950949, www.clinicaltrials.gov, July 26, 2013. Pulserocedure . Therefowww.clinicaltrials.gov (ID: NCT01950949). Informed written consent was obtained from each patient. Adult patients  scheduled for elective gastrointestinal surgery (open or laparoscopic approach) were enrolled prospectively between July 2013 and March 2014. Patients with suspected acute respiratory distress syndrome, cardiovascular diseases, neurological disease, liver and renal function abnormal, or diabetes mellitus, and those whose predicted body weight did not match actual body weight were excluded. All the patients received oral sodium phosphate solution the night before the surgery prescribed by the surgeons for gastrointestinal preparation.This study was approved by the Ethical Committee of the Chinese PLA General Hospital  and was registered at −1.h−1 through the 18G upper limb venous trocar. Anesthesia was induced using midazolam (0.04 mg.kg−1), fentanyl (3 μg.kg−1), propofol (1.5–2.5 mg.kg−1) and rocuronium (0.6 mg.kg−1), and maintained by an intravenous infusion of propofol to keep the Bispectral index (Aspect Bis Monitor XP) between 40 and 60. After tracheal intubation, a 20 G artery catheter was inserted into the left radial artery and connected to a bed-side monitor (Philips Intellivue MP50). Pressure transducers were zeroed at the mid-axillary level to atmospheric pressure. All patients were ventilated at a VT of 6, 8 or 10 ml/kg (predicted body weight) with 50 % oxygen with air without PEEP in a random order and successively for 3 min in each setting. During this period, the respiratory rate was adjusted to maintain an PetCO2 between 30 and 40 mmHg. PPV, arterial blood pressure, heart rate (HR), peak airway pressure (Ppeak), mean airway pressure (Pmean), RR, PetCO2 and BIS value were recorded 3 min after VT change while the vital signs were stable. Then the parameters under the three settings of VTs were recorded. In the case that PPV value was larger than 13 % at a VT of 8 ml/kg, 10 ml/kg of 6 % hydroxyethyl starch solution  would be given to these patients (defined as subgroup) for volume expansion over 15 min. And then the next round of recording was conducted in a new cycling of these three VT settings. All the parameters were obtained before skin incision in the supine position. During these periods, 5 mg ephedrine was administered when SAP lowered below 90 mmHg, and this case would be eliminated.Once in the operating room, an infusion of Lactated Ringer's solution was started at 4 ml.kgP-values less than 0.05 were considered statistically significant.Statistical analyses were performed using SPSS 13.0 for Windows . Normally distributed data were presented as mean ± standard deviation. Non-normally distributed data were presented as median (25–75 % interquartile range). Hemodynamic data and respiratory parameters at various VT were compared using ANOVA and Student-Newman-Keuls test. Pearson’s linear correlation was used to analyze the degree of association between variables. Sixty nine patients without heart and pulmonary complications undergoing selected abdominal operation were enrolled in this study. Patient characteristics were presented in Table To maintain the PetCO2 between 30 and 40 mmHg, the respiratory rate declined when the VT went up from 6 ml/kg to 8 ml/kg or 10 ml/kg. Meanwhile, the peak airway pressure and mean airway pressure increased along with VT , and the linear regression equation was Y =1.1691 + 1.2277X. There was also a significant linear correlation between PPVs at a VT of 6 ml/kg and 10 ml/kg (r = 0.94), and the linear regression equation was Y = 1.5888 + 1.5549X. Moreover, a significant linear correlation was observed between PPVs at a VT of 8 ml/kg and 10 ml/kg  . The correlation coefficient of the subgroup was similar with the initial observations  Fig. . The patg r = 0.9, and theThe main findings of our study were that PPV increased progressively as the VT increased in the same cardiovascular status and volume status, and that there was a significant linear correlation between any two values of PPV when VT was 6, 8 or 10 ml/kg respectively.To explore the relationship of PPVs at various VT, we enrolled patients without respiratory and cardiovascular dysfunctions in our investigation, The reason why ARDS patients were excluded was that their pathological changes might weaken the transmission of the driving pressure during mechanical ventilation , 17. AnoPrevious reports showed that tidal volume was the main factor influencing PPV during mechanical ventilation , 21. Forr = 0.92) [r = 0.97). This discrepancy could be explained by the different subjects of the two studies. In Freitas’s study, all the patients suffered from ARDS, whose mean pulmonary arterial pressure was larger than 25 mmHg; however, the enrolled patients in our study had no pulmonary inflammation or circulation system disease [r = 0.94), and that the correlation was also significant between PPVs at a VT of 8 ml/kg and 10 ml/kg (r = 0.98). Also, based on the subgroup analysis, the high correlation coefficient of different PPV values at different VT existed no matter what the patients’ volume status was.Recently, Freitas et al. found that PPV could accurately predict fluid responsiveness in septic patients ventilated at a lower VT, and there was a significant linear correlation between PPVs at a VT of 6 ml/kg and 8 ml/kg ( = 0.92) . The sim disease . MoreoveY =1.1691 + 1.2277X, the PPV was 7 % at a VT of 8 ml/kg and it reached 9 % at the VT of 10 ml/kg according to the equation Y = 1.5888 + 1.5549X. In addition, when the values of PPV in different settings of VT were compared, we found that the bigger the PPV was, the greater the difference between any two values of PPV  in patients without cardiopulmonary disorder. Secondly, the parameters were only obtained before surgical procedure. Thirdly, the subgroup in the study only covered a portion of the initially enrolled patients. Under such circumstances, it is suggested that a series of new clinical trials be designed to evaluate the relationship between the PPV values in healthy humans under other VT settings  or in the patients with heart and lung diseases . We are planning to conduct clinical trials to evaluate the relationship between the PPV values under different VT during operation, especially during some special types of surgeries like laparoscopic surgeries.In this study we have demonstrated that there was a direct linear correlation between any two values of PPV when the VT was 6, 8 or 10 ml/kg respectively. In addition, we have developed the regressive equations for the calculation of PPV values under different settings of VT. Using these regressive equations, we can calculate the PPV in another setting of VT based on the PPV at a given VT.