Post-transplant anemia (PTA) has long been a less-recognized complication in kidney transplant recipients, and its prevalence also tends to be underestimated. This study sought to evaluate the prevalence, management, and risk factors of PTA from a group of long-term follow-up Chinese kidney transplant recipients.One hundred and fifty-four adult kidney transplant recipients were followed up at Fuzhou General Hospital, China, and retrospectively studied.PTA prevalence at transplant and at 5-yearly time points after transplantation were 45.5%, 10.7%, 9.6%, 14.8%, 13.5%, and 19.6%, respectively. Overall, 38.3% of patients had been anemic at least once during the follow-up period, and 42% of these patients had recurrent anemia. Correlation analysis indicated that hemoglobin levels were associated with graft function. No correlations between anemia and age, gender, immunosuppressive regimens, or antihypertensive agents were observed. Binary logistic regression analysis suggested that serum creatinine and blood urea nitrogen were associated with the diagnosis of anemia at 1 year post-transplant. At 5 years post-transplant, only serum creatinine concentrations correlated with anemia. Although iron drugs are frequently used, erythropoietin was rarely administered in those anemic patients suffering poor graft function that necessitated such therapies.The prevalence of PTA is noticeably high, and impaired kidney graft function seemed to be the major risk factor for anemia. There is an urgent need to improve current PTA management and to establish modified guidelines for this common complication in kidney transplant recipients. In the first few weeks, and even months, after transplantation, it is relatively common for kidney transplant recipients to suffer from post-transplant anemia (PTA) due to blood loss from the surgical procedure and frequent blood sampling for repeated tests. Other factors, such as uremic toxins, iron deficiency, and erythropoietin resistance, may also account for the high incidence of PTA in this time period. DespiteThe aim of this study was to gain insight into the prevalence and risk factors of anemia from a group of long-term follow-up Chinese kidney transplant recipients, and to discuss the current management of this problem.One hundred and fifty-four adult deceased-donor kidney transplant recipients who underwent a kidney transplant between January 2005 and May 2008 were followed up at Fuzhou General Hospital, China, and enrolled if there was the potential for at least 5 years’ post-transplant follow-up. Of these patients, 14 died and 16 had graft loss prior to their 5-year post-transplant time point, and another six were lost to follow-up for various reasons. Demographic and clinical data of patients at transplant and in the subsequent 5 years during follow-up were retrieved .Patients were diagnosed as anemic according to the normative values established by the Chinese Society of Hematology, which aFor analysis of the management of PTA, data regarding iron drugs and erythropoietin therapy were entered.All patients gave signed informed consent. The study was approved by the Fuzhou General Hospital Institute Review Board (IRB00006161).t-tests or Mann–Whitney U tests were used for comparisons between two continuous variables. Chi-square tests were used for the detection of differences between proportions. Repeated measures ANOVA were used to detect differences among the means of variables of interest at each time point. Pearson’s or Spearman’s correlation coefficients were chosen to determine whether a relationship existed between two variables. All statistical analyses were performed using SPSS 11.0 software . A P value of <0.05 was considered statistically significant.Student Patients’ demographic data and the status of anemia at transplant and during follow-up are shown in Table P <0.001) decrease in mean hemoglobin levels at 5 years post-transplant compared with those at 1, 2, 3, and 4 years; 30.4% of anemic patients at the 5-year time point had a hemoglobin level lower than 9 g/dL, but only 6.7% and 7.7% were observed at 1 and 2 years, respectively.Patients at transplant had the highest prevalence (45.5%) of anemia for all recorded time points. In the proceeding 5 years, 38.3% of patients had at least one episode of anemia, and 42% of them experienced recurrent anemia. The prevalence of PTA was low in the early years; 10.7% and 9.6% at 1 and 2 years post-transplant, respectively. However, PTA increased over time as reflected by the prevalence of 19.6% at 5 years post-transplant. There was a significant  and Scr (P <0.001) levels, and lower Ccr (P = 0.001) than non-anemic patients. Of the seven patients with moderate anemia or worse, six patients (85.7%) showed a Ccr less than 50 mL/min/1.73 m2. However, poor renal excretory function did not have a causal relationship with anemia. There were two and four anemic patients who had Ccr higher than 75 mL/min/1.73 m2 at 1 and 5 years post-transplant, respectively. Some non-anemic patients did have suboptimal graft function.We selected the 1- and 5-year post-transplant variables and compared them for anemic and non-anemic patients Table . AlthougP = 0.002). At 1 year post-transplant, tacrolimus-based immunosuppressive treatment (P <0.001) and age <55 years (P = 0.025) were associated with better Ccr, while no significant correlation between Ccr and these factors were observed at 5 years post-transplant. There was no correlation between gender and ARB or ACEI use and Ccr at either 1 or 5 years post-transplant.Cyclosporin A- or tacrolimus-based immunosuppression regimens, ACEI or ARB use, gender, and age (<55 versus >55 years of age) did not affect the prevalence of anemia at either 1 or 5 years post-transplant. Female patients seemed to have lower hemoglobin levels than males at both time points . Of the 12 patients who converted from azathioprine to MMF, seven patients (58.3%) developed anemia after conversion.Patients receiving cyclosporin A, MMF, and prednisone, and patients receiving cyclosporin A, azathioprine, and prednisone were selected to determine which purine synthesis inhibitor was more likely associated with anemia. A similar prevalence of anemia was found in the earlier 4 years between these two groups of patients. Although a greater proportion of patients on MMF had anemia at 5 years post-transplant, the difference was insufficient to achieve statistical significance  also received iron therapy. However, erythropoietin was used much less often in kidney transplant recipients. None of the 15 patients with anemia at 1 year post-transplant received erythropoietin. At 5 years post-transplant, only one patient with moderate anemia (hemoglobin: 7.2 g/dL) received erythropoietin therapy.r = −0.280, P = 0.001; 5 years: r = −0.210, P = 0.001) and Scr .Univariate correlation analyses indicated that hemoglobin levels were associated with BUN  experienced recurrent anemia at later time points, suggesting susceptibility caused by some persistent clinical conditions in these patients.et al.[The PTA prevalence observed at our center at 4 and 5 years post-transplant was lower when compared with that of previous reports[et al.. That stet al.[The primary goal of the current study was to assess the prevalence and management of anemia in a group of Chinese kidney transplant recipients. Therefore, whether the routine use of iron therapy for patients at risk of anemia can effectively prevent its occurrence without increasing other morbidities is still unclear. Further prospective studies are required. According to Mrug et al., the quaACEI and ARB have been successfully used to treat post-transplant erythrocytosis. Recent evidence suggests that the angiotensin II axis plays an important role in erythropoiesis, leadingRetrospective studies, for their own limitations, can hardly provide accurate insight into the relative contribution of any single or combined immunosuppressive therapy in the development of anemia, and their shortcomings become even more overt when changes in immunosuppressive therapy have been made.et al.[Previous studies have suggested that both MMF and azathioprine could lead to anemia. The queet al. reportedet al.-15.PTA is a common complication for long-term follow-up kidney transplant recipients, and is often overlooked by transplant physicians. Kidney graft function is associated with both the diagnosis of anemia and hemoglobin levels. Iron medications should be administered in a timely manner in patients with PTA, while erythropoietin therapy should be initiated in anemic patients whose kidney grafts have already failed to produce sufficient erythropoietin to maintain hemoglobin levels.ACEI: Angiotensin-converting-enzyme inhibitors; ANOVA: Analysis of variance; ARB: Angiotensin receptor blockers; BUN: Blood urea nitrogen; Ccr: Calculated creatinine clearance; MMF: Mycophenolate mofetil; PTA: Post-transplant anemia; Scr: Serum creatinine.The authors declare that they have no competing interests.ZW performed the study, collected and analyzed the data, and wrote the paper. JG performed the study and wrote the paper. LL analyzed the data and wrote the paper. WW and SY performed the study. JT designed the study. JT takes responsibility as the guarantor for the content of the article. All authors read and approved the final manuscript.


S. mansoni before treatment (G-II) and infected by S. mansoni after treatment (G-III). Renal function was evaluated by tubular and glomerular biomarkers and through urinary MCP-1. Patients’ mean age was 23.2±13 years. There was no statistically significant difference between the groups regarding tubular and glomerular function evaluated through the traditional biomarkers. MCP-1 was higher in G-II and G-III, when compared to G-I; p=0.009 and p=0.007, respectively. There was no difference when comparing groups G-II and G-III (p=0.892). Although it was not different among the groups, there was a significant correlation between albuminuria and MCP-1. There was a significant increase in urinary MCP-1 levels in patients with schistosomiasis mansoni, which was associated with albuminuria. This protein has a role in the recruitment of monocytes to injury and inflammation sites . The increase of MCP-1 in the urine evidences that there is silent renal inflammation in these patients and the inflammatory status is not interrupted by specific treatment of the offending agent. Our findings suggest that urinary MCP-1 can be a sensitive marker of renal injury in patients with schistosomiasis mansoni. The aim of this study is to investigate renal markers and the biomarker MCP-1 in patients with schistosomiasis mansoni. This is a cross-sectional study with 85 patients aged 5 to 48 years, with a confirmed diagnosis of schistosomiasis mansoni through the Kato-Katz method. The patients were divided in three groups: control (G-I); infected by  Schistosoma mansoni can lead to slow and progressive renal damage in addition to membranoproliferative glomerulonephritis (MPGN).The association between infectious endemic diseases and the kidney has already been described . Renal iRoutine markers for renal damage  lack sensitivity. Even the use of microalbuminuria, one of the most sensitive markers of renal damage currently used in clinical practice is controversial and some studies have suggested that higher normal range values can be related to progressive renal damage . RecentlTo date, there has been no study regarding renal involvement in patients with chronic schistosomiasis mansoni. The aim of this study is to investigate renal markers and the biomarker MCP-1 in patients with schistosomiasis mansoni.In compliance with the ethical rules governing research on human health provided in Resolution 196/96 of the National Health Council of Brazil, this project was submitted to the Research Ethical Committee of the Department of Physiology and Pharmacology of Universidade Federal do Ceara and approved under n. 165/09. Before selection, all families attended a lecture detailing the objectives and procedures of this study. Those who chose to participate had the study explained in full at home. Informed written consent was obtained from the study participants or, in the case of minors, from their parents or guardians.Biomphalaria straminea is the intermediate host of schistosomiasis mansoni. Patients older than 60 and younger than 2 were excluded, as well as those with diabetes mellitus, hypertension, systemic lupus erythematosus, rheumatoid arthritis, chronic kidney disease and any other condition that could cause kidney injury. Moreover, a urine microscopy study was performed to exclude significant leukocyturia (higher than 5 white blood cells per high-power field). A total of 85 individuals were selected, according their status for S. mansoni infection. Group I (GI): non-infected subjects, demonstrated by negative serology through ELISA and Kato-Katz methods - n=24; Group II (GII); infected subjects with no previous treatment (n=30) and group III (G III) infected subjects treated between 6-12 months before study inclusion. In the last group, reinfection was excluded by performing new Kato-Katz test (3 samples) at study inclusion. This is a cross-sectional study carried out in Planalto do Cajueiro, a district in the town of Maranguape, Ceara State, Northeast of Brazil. This district is a small community distributed across five urban blocks, according to a survey carried out by the town hall. The area is surrounded by two streams and S. mansoni. After this analysis, feces were collected for Kato-Katz testing [Blood samples were collected to perform sorting of individuals by ELISA using soluble adult worm antigen (SWAP) of  testing , to dete® kits and the results were used to estimate fractional excretion. Urinary MCP-1 measurement was performed through ELISA using the R&D Systems® kit, Inc . The MCP-1 value was corrected by urinary creatinine.Serum creatinine and urinary albumin were determined by the kinetic-colorimetric method and the results were expressed in mg/dL. After the sample analysis, the eGFR was calculated by the Cockcroft-Gault  and SchwS. mansoni eggs in the stool were treated with Praziquantel® at a dose of 60 mg/kg of body weight in a single dose. The drug was dispensed under medical supervision at the community’s public health center. Patients in the GIII had their treatment efficacy and no reinfection confirmed by a new Kato-Katz test.All patients who were positive for the presence of Data were expressed as mean ± standard deviation. Statistical analysis was carried out using the SPSS program, version 19.0 . After testing for normality using the K-S test, differences between the means of multiple variables were inferred trough One-Way ANOVA test and Bonferroni post-test and the correlations were evaluated according to Pearson’s test. The established confidence interval was 95%, and “p” values <0.05 were considered statistically significant.Patients’ mean age was 23.2 ± 13 years. There was no significant difference regarding age (p=0.50) and gender (p=0.18) among the groups.The cut-off value used for ELISA was 0.283 (±2SD). The mean reading of ELISA in groups I, II, III  were, respectively, 0.18, 0.48 and 0.62. None of ELISA tests were performed after treatment.S. mansoni eggs in all cases and 3 cases also had other parasitic diseases, while in the post-treatment group (GIII), only 1 patient had other parasitic infection, with Trichuris trichiura being the other parasite found.In the infected group (GII), there were There was no difference regarding tubular function among the three groups . RegardiMCP-1 levels were significantly higher in GII (178 ± 97pg/mg-Cr) and GIII (175 ± 87pg/mg-Cr), when compared to GI (123 ± 48pg/mg-Cr), p=0.009 and p=0.007, respectively, but there was no difference when comparing GII and GIII (p=0.892) . Althoug Although the intensity of the humoral response to the parasite can cause some damage by the immune complexes deposition, we found no correlation among IgG-ELISA and the markers used as MCP-1 , albuminuria  and GFR .For the first time, we have shown that schistosomiasis mansoni infection can induce a chronic renal inflammatory status, demonstrated by an increment in urinary MCP-1. However, this inflammatory status is not interrupted by the specific treatment of the offending agent.Most patients in the present study were young with low probability of underlying kidney disease. Although there was no difference among the three groups in relation to urinary albumin excretion rate, an increase in urinary MCP-1 was observed in patients with active or treated schistosomiasis mansoni infection. This finding suggests that urinary MCP-1 may be a more sensitive marker of renal damage than urinary albumin excretion rate.In other renal diseases, urinary MCP-1 has been correlated with urinary albumin excretion rate, glomerular filtration rate reduction and other features of renal injury. To date, studies have included metabolic (diabetes mellitus), immunologic (lupus nephritis) and genetic  kidney disorders ,13. To tAnother marker of glomerular kidney injury that has been studied is cystatin C. It is an endogenous marker of renal dysfunction; in fact, it is a more adequate marker of GFR, rather than a primary AKI biomarker. Furthermore, there are also tubular biomarkers such as Kidney Injury Molecule-1(KIM-1), Neutrophil gelatinase-associated lipocalin (NGAL), Interleukin-18 and N-acetyl-β-D-glucosaminidase (NAG). KIM-1and NGAL have been studied in humans and rodents. KIM-1 is not detectable in normal kidney tissue or urine, but is expressed at very high levels in kidney tubular epithelial cells of rodents and humans after ischemic injury and NGAL is expressed by neutrophils and epithelial cells including those of the proximal tubule .Trypanosoma cruzi Y strain [In a recent study, kidney injury was characterized by high levels of proteinuria, Kidney Injury Molecule-1 (KIM-1) and urea, in guinea pigs infected and non-infected with Y strain .It is noteworthy the fact that even 6 months after schistosomiasis mansoni treatment, there was no reduction in urinary MCP-1. Although most patients had albumin excretion rate within the normal range, a positive and significant correlation was observed between albuminuria and urinary MCP-1. It is already know that even patients with high-normal albumin excretion rate are at high-risk of developing chronic renal failure. So, this study suggest that young patient with schistosomiasis mansoni infection are at higher risk to develop clinically significant kidney injury than elder patients.S. mansoni and this correlated with albuminuria levels, which were within normal limits. As schistosomiasis mansoni is a disease that predominates in youngerindividuals, these patients are at higher risk of renal function loss and should benefit from measures to slow kidney disease progression. MCP-1 seems to be a useful early biomarker for schistosomal nephropathy.These data strongly suggests that there was a chronic and asymptomatic inflammation in these patients infected with


P = 0.04). Patients presenting with acute COPD had significantly lower percentage of predicted PEFR than those with CHF. These results suggest that PEFR may be useful in differentiating COPD from CHF. This study should be expanded to the prehospital setting with a larger number of subjects.Dyspneic patients are commonly encountered by Emergency Medical Service (EMS). Frequent causes include Chronic Obstructive Pulmonary Disease (COPD) and Congestive Heart Failure (CHF). Measurement of peak expiratory flow rate (PEFR) has been proposed to help differentiate COPD from CHF. This prospective, cohort, pilot study was conducted to determine if PEFR in patients with an exacerbation of COPD were significantly different than CHF. Included were patients presenting with dyspnea plus a history of COPD and/or CHF. A PEFR was measured, values were compared to predicted average, and a percentage was calculated. Twenty-one patients were enrolled. Six had a diagnosis of COPD, 12 CHF; 3 had other diagnoses. Mean percentage of predicted PEFR with COPD was 26.36%, CHF 48.9% ( Dyspnea, a common cause of Emergency Medical Service (EMS) calls, can result from problems involving many organ systems. Some of the more frequently encountered scenarios are Chronic Obstructive Pulmonary Disease (COPD) and/or Congestive Heart Failure (CHF) which have different treatment regimens . It is et-test with P = 0.05 indicating a significant difference.This prospective, cohort, pilot study was conducted in the ED over a two-month period. A convenience sample of patients were enrolled based on their chief complaint and suspected history as recorded in triage or by EMS. Only those patients who presented with a history of COPD or CHF were included in the study. Patients were excluded if they were unable to cooperate with peak flow testing, or if any interventions, other than oxygen administration, were initiated by EMS, nursing or medical staff prior to obtaining the PEFR measurements. Once the patient was placed in a room, investigators obtained informed consent and a brief history. The patient was then given instructions on how to perform the peak expiratory flow test, and three attempts were made. The peak flow measurements were taken by one of the authors (J. E. Gough) or one of the study assistants trained in measuring PEFR. The treating physicians were blinded to the results of the PEFR testing. The highest peak expiratory value was recorded and considered the patient's best effort. This value was then compared to a standard predicted value based on the patient's height and age. A percentage of predicted value was calculated and used for the purpose of statistical analysis . The patP value was calculated as 0.04 .There were 6 patients enrolled which had a known history of COPD. These patients had a mean PEFR of 35.8%; all received a final diagnosis of COPD. There were twelve other patients with no history of COPD, and these patients had a mean PEFRF of 40.1%. There was no significant difference in peak flow between patients with a history of COPD and those without (P = 0.05).Of the twelve patients with a known history of CHF, the PEFR of 48.8%, and 11 received a final diagnosis of CHF. The six patients enrolled who had no history of CHF had a mean PEFR of 26.3%. Those without a history CHF had a significantly lower PF than those with a history of CHF (One patient had a history of both CHF and COPD. The PEFR for this patient was 79.3%, and the diagnosis for this visit was CHF exacerbation. Respiratory distress and shortness of breath are frequent complaints which account for approximately 13% of EMS transports . SimilarUtilization of a peak flow test has been proposed as a simple, low cost, and time-effective instrument to help differentiate COPD from CHF as a cause of dyspnea , 4, 11. Limitations of this study include a small number of patients enrolled and the ED setting rather than EMS environment. The authors first sought to determine if the PEFR would potentially be useful before expanding the study to the prehospital setting. Study enrollment was limited by several factors, the first of which was the sampling method utilized as patients were only enrolled when one of the study investigators was present in the ED. Furthermore, a number of patients had interventions such as nebulizer treatments or medications initiated prior to obtaining PEFR. These limitations preclude the authors from determining how many patients were lost to enrollment. Although peak flow meters are easy to use and interpret, a major limitation to their use is that results are dependent on patients' understanding and effort , 5. The results of this study demonstrate that in this population there is a difference between the PEFR values among patients with COPD as compared with CHF. Although the sample population is small, these data suggests that COPD patients show a lower percentage of predicted value for peak expiratory flow than those with CHF. This study should be continued in the prehospital setting with a larger sample size to better assess the utility of using this method among EMS personnel.


A blood pressure drop after bevacizumab administration and its clinical significance have not been previously reported.Blood pressure data at 0, 90, and 180 min after a total of 162 bevacizumab administrations in 81 advanced colorectal cancer patients were retrospectively investigated.vs 162 days; P=0.02). Furthermore, the proportion of patients who required intervention with antihypertensive drugs during bevacizumab treatment was significantly higher in group A than in group B (36% vs 4% P<0.01).Twenty-five patients (30%) demonstrated an average temporary drop of 20 mm Hg or more in systolic blood pressure. We classified these 25 patients as group A and the others as group B. Median time-to-treatment failure (TTF) was significantly longer in group A than in group B (291 This study suggests that a temporary blood pressure drop after bevacizumab administration could be a predictive marker for bevacizumab treatment. Bevacizumab is a recombinant humanised monoclonal antibody that binds to vascular endothelial growth factor (VEGF) A and is now widely used for the treatment of colorectal cancer in combination with other cytotoxic drugs  (Bevacizumab was administered in combination with one of the following regimens (fluorouracil/leucovorin/irinotecan (FOLFIRI), fluorouracil/leucovorin/oxaliplatin (mFOLFOX6), fluorouracil/leucovorin (sLV5FU2), capecitabine/oxaliplatin (XELOX), or capecitabine) as previously reported (χ2-test or Fisher’s exact test for dichotomous variables or the Mann–Whitney U-test for continuous variables. Time-to-treatment failure (TTF) was defined as the interval between the date of initiation and discontinuation of treatment and estimated by the Kaplan–Meier method. Patients not experiencing an event were censored at the last follow-up visit. Comparisons of the time-to-event distributions were made using the log-rank test, with the hazard ratio (HR) and its 95% confidence intervals (CIs) calculated from a Cox regression model. All P-values are two-sided. All statistical analyses were performed using SPSS version 11.0J .Baseline patient characteristics were compared using the Patient baseline characteristics are summarised in P=0.02)  compared with group B  with an HR of 0.53  .Since hypertension associated with bevacizumab treatment has been well documented (First, the drop in blood pressure was a temporary phenomenon and blood pressure returned to baseline levels between 90 and 180 min after bevacizumab administration  and 2. ISecond, this phenomenon was observed through two separate cycles.Third, in the first cycle bevacizumab was infused over 90 min and no other drugs were infused until 90 min.Out of the 25 patients classified as group A, 10 received anti-epidermal growth factor receptor monoclonal antibody and blood pressure was monitored at 0 and 60 min after the administration of this antibody during the first cycle. Mean change in systolic blood pressure was 3 mm Hg, and no patients demonstrated a blood pressure drop of 20 mm Hg or more. These results also support the idea that a blood pressure drop after bevacizumab administration was not merely caused by a result of chance, physiological variability or inaccuracy of blood pressure measurement.In line with our current results, P=0.02; vs 4% P<0.01; Next, we investigated the association between this phenomenon and TTF because recent studies have suggested a positive correlation between hypertension after bevacizumab treatment and clinical outcome P=0.02; . FurtherIn summary, our current study demonstrates that, in some patients, blood pressure drops temporarily after bevacizumab administration to varying degrees, and that this phenomenon is associated with a longer TTF. Since this phenomenon was observed from the first cycle of bevacizumab treatment, it could predict the clinical course of treatment at an earlier time point than bevacizumab-related hypertension. Future prospective studies with a larger cohort are warranted to verify the results of current study and to clarify its underlying mechanism.


The artefacts affecting arterial wave morphology may compromise recorded values of arterial blood pressure (ABP) and can lead to therapeutic errors. The aim of this study is to evaluate the errors between invasive and noninvasive arterial pressure values, the incidence of artefacts due to an inadequate dynamic response of the transducer-tubing system, and their detection by the ICU staff.Seventy-five consecutive patients  admitted to the ICU for heterogeneous pathologies were enrolled. Inclusion criteria were: the presence of an intra-arterial catheter (IAC) for invasive blood pressure monitoring, and age >18 years. Pregnancy was excluded. At admission and every time the IAC was replaced we acquired invasive systolic, diastolic, and medium arterial pressure values  during hemodynamic stability ; at the same time, noninvasive systolic and diastolic arterial pressure values  were measured with a sphygmomanometer at the same arm of the IAC. Noninvasive medium arterial pressure (Ni-MP) was calculated as follows: (SP + 2DP)/3. At every time of the study, before ABP value acquisition, medical and nursing staff answered a questionnaire on the reliability of the arterial waveform. The staff could perform the fast flush test if considered appropriate. However, the fast flush test was executed by the main investigator at the end of questionnaire in all patients. Bland-Altman analysis was performed.We compared 130 pairs of Ni-SP, Ni-DP and Ni-MP and I-SP, I-DP and I-MP. The mean bias between Ni-SP and I-SP was -11 mmHg (limit of agreement (LoA) -43.6 to 21.4 mmHg). The mean bias between Ni-DP and I-DP and between Ni-MP and I-MP was 6.1 mmHg (LoA -15.5 to 27.7 mmHg) and 0.37 mmHg (LoA -21.0 to 21.7 mmHg), respectively. We performed the fast flush test 130 times; an inadequate dynamic response of the transducer-tubing system was observed 55 times: in 45 cases the arterial signal was underdumped and in 10 cases was overdumped. The arterial dumping was correctly detected by the medical staff in 95% of cases, by nursing staff and postgraduates in 35% of cases.The bias between invasive and noninvasive ABP measure can be relevant and mislead in the therapeutic management. These errors can be avoided by identifying the artefacts that affect arterial signal and so the ICU staff must pay attention to the recognition of arterial dumping in critically ill patients.


The baroreceptors in the neck and aortic arch are important regulators of sudden blood pressure changes. They are innervated by CN IX and X and synapse in the brainstem. Baroreceptor failure is an under-recognized cause of recurrent syncope, orthostatic hypotension, and volatile hypertension, which is refractory to and may in fact worsen with conventional treatments. Baroreflex failure can be the result of neck and chest radiation, head and neck surgery, and cerebrovascular accidents involving the brainstem nuclei. The management of baroreflex failure is a challenge since patient education, lifestyle changes, and family support are extremely important in managing blood pressure. Leg exercises and Thrombo-Embolic Deterrent Stockings (TED) stockings are important in treating orthostatic hypotension. Clonidine is the antihypertensive of choice for supine hypertension. Low-dose benzodiazepines are helpful in suppressing sympathetic surges. We have encountered two patients with baroreflex failure after chemotherapy and radiation to the neck or upper chest. Temporal relationship between symptoms onset and the history of head, neck, and upper chest radiation or trauma is important in reaching a diagnosis. Baroreceptors monitor sudden changes in blood pressure and buffer these changes to prevent excessive fluctuations  in blood pressure. Baroreflex failure can lead to significant volatility in blood pressure values leading to either orthostatic hypotension or supine hypertension. It can present as recurrent syncope, which is refractory to conventional treatments. Without understanding the pathophysiology behind the baroreflex failure, managing these patients can be challenging. We have encountered two patients with baroreflex failure after chemotherapy and radiation to the neck or upper chest .A 74-year-old male presented with multiple episodes of lightheadedness and the feeling of ‘passing out’ while he was getting out of his bed and walking. He had a 40-pack-year smoking history, and his past medical history was significant for nasopharyngeal cancer for which he received radiation and chemotherapy 6 years earlier. He had no history of diabetes or hypertension. Examination revealed significant orthostatic changes in blood pressure, 168/100 mmHg upon lying down and 102/44 mmHg upon standing up. The rest of his physical exam was negative. Extensive laboratory, cardiac, and neurological testing came back within normal limits. His symptoms did not improve with intravenous fluids. Normal saline infusion worsened his supine hypertension.A diagnosis of baroreceptor failure was made on the basis of the history of neck radiation, tilt table test, depressor response (hypotension and widened pulse pressure response) to a small dose of clonidine. Tilt table testing showed progressive orthostatic hypotension without a significant change in heart rate. A variety of non-pharmacologic measures such as increasing dietary salt and caffeine, TED stockings and leg muscle exercising after prolonged standing were recommended to decrease fluctuations in blood pressure. He was treated with low doses of alprazolam, clonidine, and fludrocortisone. On follow-up, the patient felt better but still had occasional postural lightheadedness.A 58-year-old Caucasian male was found to have a large right upper lung mass, which was subsequently confirmed to be small cell carcinoma of the lung by endobronchial biopsy. The cancer was complicated with superior vena cava (SVC) syndrome. The patient then received two cycles of Cisplatin and Etoposide-based chemotherapy concurrently with a radiation therapy to the lower neck, right lung, and mediastinum. The radiotherapy was stopped at a total dose of 4,640 cGy because of the development of a significant esophagitis. He also became hypertensive with severe tachycardia. His hypertension resolved with medication; however, he later developed persistent orthostatic hypotension that was refractory to intravenous fluids. His blood pressure was 130/71 at supine level, 113/48 upon sitting up, and 73/46 upon standing up. The rest of his physical exam as well as extensive laboratory, cardiac testing were normal. Normal cortisol levels ruled out adrenal insufficiency. A diagnosis of baroreceptor failure was made based on the history of extensive radiotherapy. The patient was started on a liberal sodium diet, midodrine, fludrocortisone, and TED stockings. He was also advised to do physical activities such as leg exercises to decrease fluctuations in blood pressure. His orthostatic hypotension has since improved on follow-up.Baroreceptors are mechanoreceptor sensory neurons that are excited by stretching of the corresponding blood vessel. They act through an instantaneous negative feedback response system called baroreflex to buffer huge changes in blood pressure .Baroreceptors can be subclassified into high-pressure arterial baroreceptors and low-pressure volume receptors or cardiopulmonary receptors. Among the arterial baroreceptors, the most important are carotid sinus baroreceptors and aortic arch baroreceptors. The carotid baroreceptors are located in carotid sinuses, close to the bifurcation of the internal carotid artery from the common carotid artery. They are innervated by the sinus nerve of Hering, a branch of the glossopharyngeal nerve (CN IX). Aortic arch baroreceptors can be found in the tunica adventitia of the aorta in the aortic arch and innervated by the vagus nerve (CN X). They synapse in the nucleus tractus solitarus, which in turn modulates activity of autonomic nervous system. Both sympathetic and parasympathetic pathways serve as the efferent pathway. The effectors of baroreceptor reflex include: sino-atrial node, atrioventricular node, cardiac muscle cells, and arterial and venous smooth muscles.Standing up from a lying position can cause a significant reduction in blood volume as 300–800 ml blood pools into the lower extremities. This drastic drop of venous return leads to decreased venous return, decreased cardiac output, hypotension, and inadequate perfusion of vital organs. In response to hypotension, the sympathetic nervous system is activated. Peripheral vasoconstriction by catecholamine release from nerve endings lead to increased venous return, and ultimately, increased preload. On the cardiac muscles and nodal cells, it has inotropic, chronotropic, and dromotropic effects. It augments cardiac conduction, contractility, and heart rate, leading to increased stroke volume and cardiac output. All of these actions ultimately restore blood pressure and perfusion to the vital organs .Baroreflex failure can occur after neck radiation, surgery and cerebrovascular accidents involving the brainstem nuclei, and results in improper regulation of autonomic neurons that leads to impaired blood pressure regulation. Neck irradiation can be complicated with a late-onset of baroreflex failure . DespiteBaroreflex can be measured by methods involving the application of vasoactive drugs , Valsalva maneuver, and mechanical manipulation by the neck chamber technique that produces a negative/positive local pressure for the baroreceptors in the neck region . These tPatients with baroreflex failure typically present with postural lightheadedness, orthostatic hypotension, syncope and also labile hypertension, which can also be found in autonomic nervous system failure. In fact, baroreflex failure is a part of the spectrum of autonomic nervous system failure and typically presents with systolic and diastolic hypertensive episodes, tachycardia, and hypotension alternating with relative bradycardia at rest .Differential diagnosis for orthostatic hypotension in these cases include paraneoplastic autonomic neuropathy (PNAN), which is most often seen in patients with small cell lung cancer. The prominent clinical findings of PNAN other than orthostatic hypotension include bowel hypomotility, intestinal obstruction, bladder dysfunction, pupillomotor and sudomotor dysfunction, and xerophthalmia. Both our patients did not have any other signs of autonomic dysfunction other than orthostatic hypotension.Although PNAN is often associated with anti-Hu antibodies and anti-CV2/CRMP-5 antibodies , they weWe made the diagnosis of baroreflex failure based on the clinical picture of orthostatic hypotension, past medical history of head, neck and/or upper chest radiation, normal electrolytes, and the systematic exclusion of other possible diagnoses. Tilt table test showed progressive orthostatic hypotension and no significant change of heart rate. These findings excluded vasovagal and reflex syncope as the possible cause of syncope as bradycardia and hypotension are the expected findings.The time of onset can vary from patient to patient based on the volume status, baseline activities, family support, and co-morbid conditions such as hypertension, diabetes, arthritis, and dementia. The first patient had recurrent syncope attacks but tolerated the symptoms for several years before coming to the hospital. With the second patient, the symptoms were of sudden onset and severe enough to seek more prompt medical attention.Baroreflex failure is a therapeutic challenge since both the hypertension and hypotension are often difficult to control with conventional therapy. In addition, many medications that do not elicit blood pressure changes in healthy subjects may have a dramatic effect in baroreflex failure patients . Drugs tManagement typically includes non-pharmacological and pharmacological components. The first and foremost step of non-pharmacological measures should be education of the patient and his/her family about the importance of measuring his/her blood pressure frequently. Second, timing of food and water should be carefully adjusted since carbohydrate ingestion can lower blood pressure by 30–40 mmHg. It can be useful in managing supine hypertension at night. Drinking water also has a significant, dose dependent, pressor effect in these patients. Sixteen ounces of water raised the systemic blood pressure by 20–40 mmHg in a clinical trial presented by Jordan et al. . Oral flPharmacologically, clonidine, a centrally acting alpha-2 agonist, is the most effective agent and hence the antihypertensive of choice. It works centrally and peripherally to attenuate sympathetic activation and limit the hypertensive episodes . In the Fludrocortisone can cause salt and water retention and alleviate orthostatic hypotension. In order to see the mineralocorticoids effect, patients should be encouraged to consume a salt-liberal diet or take a gram of salt tablet at breakfast and lunch.Baroreflex failure following radiotherapy is an under-recognized cause of labile blood pressures with orthostatic changes and recurrent syncope. Diagnosis can be challenging since the majority of signs and symptoms overlap with those of autonomic failure. Timing of symptoms onset and a history of head, neck or chest radiation are important hints. A clear temporal relationship can make the diagnostic process relatively straight forward whereas a huge time gap between radiation and symptoms onset can obscure the diagnosis. Radiation is a common cause of baroreceptor damage. While neck irradiation is a well-recognized cause, intensive upper chest irradiation may have similar consequences due to damage to the baroreceptors in the aortic arch. Both the hypertension and hypotension are often difficult to control with conventional therapy. Clonidine is the antihypertensive of choice for supine hypertension. Low-dose benzodiazepines are helpful in suppressing sympathetic surges. Physical maneuvers like periodic squatting help maintain blood pressure when upright. Fludrocortisone, midodrine and TED stocking are the treatments of choice for orthostatic hypotension.


There is a rising incidence of chronic kidney disease that is likely to pose major problems for both healthcare and the economy in future years. In India, it has been recently estimated that the age-adjusted incidence rate of ESRD to be 229 per million population (pmp), and >100,000 new patients enter renal replacement programs annually.We cross-sectionally screened 6120 Indian subjects from 13 academic and private medical centers all over India. We obtained personal and medical history data through a specifically designed questionnaire. Blood and urine samples were collected.The total cohort included in this analysis is 5588 subjects. The mean ± SD age of all participants was 45.22 ± 15.2 years (range 18–98 years) and 55.1% of them were males and 44.9% were females. The overall prevalence of CKD in the SEEK-India cohort was 17.2% with a mean eGFR of 84.27 ± 76.46 versus 116.94 ± 44.65 mL/min/1.73 m2 in non-CKD group while 79.5% in the CKD group had proteinuria. Prevalence of CKD stages 1, 2, 3, 4 and 5 was 7%, 4.3%, 4.3%, 0.8% and 0.8%, respectively.The prevalence of CKD was observed to be 17.2% with ~6% have CKD stage 3 or worse. CKD risk factors were similar to those reported in earlier studies.It should be stressed to all primary care physicians taking care of hypertensive and diabetic patients to screen for early kidney damage. Early intervention may retard the progression of kidney disease. Planning for the preventive health policies and allocation of more resources for the treatment of CKD/ESRD patients are imperative in India. Chronic kidney disease (CKD) is emerging to be an important chronic disease globally . One reaThirteen academic and private medical centers in India participated in the study under the name of “Screening and Early Evaluation of Kidney disease - SEEK.” Any Indian male and female with age over 18 years are eligible to participate in the screening. It was conducted between June 2005 to May 2007, coordinated from the Brigham and Women’s Hospital in Boston, Massachusetts, a teaching affiliate of Harvard Medical School. The protocol was approved by the Partner’s Institutional Review Board (IRB) as well as by individual centers own institutional IRBs. Signed or verbal informed consent (confirmed by a witness) was obtained before administering the questionnaire, taking measurements or blood collection. The database is based at the Brigham and Women’s Hospital.A structured questionnaire was developed and pre-tested in the pilot study of 500 subjects carried out at one center in South India  was calculated using the formula “weight (Kg) / height (m2).” The waist to hip circumference ratio (WHR) was calculated by using the waist circumference at the narrowest circumference between the lower costal margin and the iliac crest. Hip circumference was measured at the maximum circumference at the level of the femoral trochanters.In order to get a standardized blood pressure (BP) measurement, a protocol per American Heart Association guidelines  and a po- 1.54 × (Age)- 0.203 ×  × (1.212 if African American) was used [Random blood samples were collected. Blood was sent to a central laboratory. Quality control for temperature transporting specimens was checked and confirmed; i.e., 4–9 degree Celsius. Serum creatinine was measured using Jaffe Colorimetric method on a Roche Hitachi 912 analyzer. The instrument was calibrated  using the Cleveland Clinic Foundation (CCF) creatinine panel. Regression analysis was carried out to calculate a formula to convert creatinine values obtained at the SRL-Ranbaxy laboratory (SRL) to the CCF values as follows: CCF creatinine = −0.13 + SRL creatinine * 0.99. Urine protein was detected by dipstick method (Bayer Multistix 10 SG). A modified MDRD-3 equation GFR(mL/min/1.73 m2) = 175 × (Scr)Hypertension was defined as SBP/DBP > = 140 /90 mm of Hg  or if thDiabetes was defined as fasting blood sugar FBS > = 126 or random blood sugar > = 200 or on any medications for diabetes mellitus (ADA definition) [According to the International Diabetes Federation (IDF) criteria, abdominal obesity was defined waist circumference of ≥94 cm in men and ≥80 cm in women .CKD stages were defined using NKF-KDOQI guidelines (eGFR < 60 ml/min/1.73 m2 or proteinuria > 1+ on dipstick) . Urine pSelf reported ischemic heart disease was taken as present if there was a self reported history of a myocardial infarction, percutaneous angioplasty or coronary artery bypass surgery (CABG).All patients with CKD diagnosed in camps received the reports along with a referral to the local hospitals/clinics.IBM SPSS Statistics for Windows, version 19, 2010, SPSS Inc., an IBM company, was used. In the descriptive analysis, continuous variables were expressed as mean ± standard deviation (SD) and categorical variables were expressed as count (percentages). While making no assumption about the distribution of data, normality distribution testing of the continuous variables was performed using the non-parametric test; Kolmogorov-Smirnov test (KS-test). Univariate analyses comparing distributions of socio-demographic and clinical/historical measures between CKD groups was performed using independent unpaired student t Test for normally distributed continuous variables and Mann–Whitney U Test for non-normally distributed continuous variables. For categorical variables we used Pearson chi-square test. Fisher’s exact test was used when there was one or more of cells with an expected frequency <5. We performed spearman correlation analysis to study the relationship between eGFR and other variables. The values of Spearman’s rho and the p-value have been reported.2 respectively. The remaining baseline demographics, clinical and laboratory data were summarized in Tables Six thousand one hundred and twenty subjects were screened as part of the SEEK-India project. We recruited subjects through 53 screening camps in 12 cities across India representing almost all Indian regions , anemia (40.7%) and diabetes (31.6%)  and low hemoglobin level were correlated with decreased eGFR in the CKD subgroup.A recent study on 3398 central government employees in India reported ~13-15% prevalence of early stages of CKD , similar in magnitude to our results, although they used microproteinuria, hematuria and/or leukocyturia as indicators of kidney damage. A study from Apollo Hospital in Chennai  reportedAgrawal et al.  performeThe SEEK-India study is similar in design to the KEEP study conducted by the National Kidney Foundation in the USA . It is aReports from other countries participating in the Global SEEK project have been published. The results of SEEK-Thailand study using a cluster randomized design showed 17.5% prevalence of CKD . The SEEIncreased prevalence of CKD could be partly explained by the high prevalence of risk factors like diabetes and hypertension in the screened population . The prevalence of diabetes and hypertension in India varied widely in many studies and ranged from 6-20% and 13-58%, respectively ,28. AmonDespite the high prevalence that we reported in our study, subjects in our cohort had a low awareness of CKD. Only 7.9% of subjects knew that they had CKD compared to 1.9% in SEEK-Thailand and 7.1% in SEEK-Saudi Arabia. This might reflect the lack of healthcare resources available to the population. When performing sensitivity analysis using CKD-EPI equation, the prevalence of CKD in our study was 16.4% (versus 17.2% using MDRD-3 equation). A recently published study aimed at evaluating the applicability of CKD-EPI equation to eGFR in Chinese patients of different stages of CKD , compareIn our SEEK-India cohort, the prevalence of CKD was 16.4%. CKD Stage 1 was 8%, slightly higher than the one estimated using MDRD-3 (7%). However, prevalence of CKD stages 2 and 3 were 3.2% and 3.3% respectively, slightly lower than MDRD-3 (4.3% and 4.3% respectively). It also showed similar results to MDRD-3 in CKD stages 4 and 5 (0.8% each). Similar comparisons are supported by other studies in UK  where itSixty three percent of our total sample, and almost half of the CKD group (52.6%), earns < $125 a month. Poverty and lack of education often go together. Among the CKD population, 37.6% had less than high school which may have contributed to this lack of awareness. In the NHANES study 11.6% of men and 5.5% of women in CKD stage-3 knew about their disease .Our study had several potential limitations. We used a convenience study design rather than a cluster randomization design and/or household surveys. We mirrored our design on that used by the NKF KEEP cohort in order to bench mark our community based cohort with the results of KEEP. However our sampling strategy may not be ideal for evaluation of true prevalence. Another limitation was the single measurement of serum creatinine and urine albumin. Repeated measures might improve the precision around our reporting of the data. Furthermore, a subsequent measurement after 3 months might have provided additional insights into the chronicity of the disease. Additionally, the prevalence of CKD might have been overestimated by using the Bayer’s multistix 10 which detects urine protein, not albuminuria. Another limitation is that we used the MDRD equation using the race factor for compatible for Americans. However, there are concerns of the application of the definition and staging system for current eGFR estimating equations to the Indian population. Different diet and muscle mass in the Indian as compared to the North American populations may lead to both differences in the normal level for kidney function in the population as well as the relationship between creatinine and GFR as reflected in the estimating equations; where these equations have been predominantly developed and validated.In conclusion, in this large, community-based cross-sectional study using a convenience sample of SEEK, we successfully carried out CKD screening using simple tests to estimate e-GFR and protienuria. The prevalence of CKD was observed to be 17.2% with ~6% have CKD stage 3 or worse. CKD risk factors were similar to those reported in earlier studies. Awareness was observed to be low. This data supports the importance of improving the education and early detection of CKD. It should be stressed to all primary care physicians taking care of hypertensive and diabetic patients to screen for early kidney damage. Early intervention may retard the progression of kidney disease. Planning for the preventive health policies and allocation of more resources for the treatment of CKD/ESRD patients are imperative in India.The authors declare that they have no competing interest.BVM and AKS – conceived and designed the study. AKS – acquired funding, supervised the overall execution of the study. BVM – cleaned the database. YMKF – analyzed and interpreted the data. YMKF, BVM, KKS and AKS – wrote the manuscript. All other co-authors – conducted and supervised the study procedures and the operational execution in the local Indian centers. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/14/114/prepubSEEK Project – Screening Questionnaire.Click here for file


Endoglin is involved in the regulation of endothelial function, but there are no studies concerning its relation with hypertension- and diabetes-associated pathologies. Thus, we studied the relationship between plasma levels of soluble endoglin and cardiovascular alterations associated with hypertension and diabetes.We analyzed 288 patients: 64 with type 2 diabetes, 159 with hypertension and 65 healthy patients. We assessed the relationship of soluble endoglin plasma levels measured by enzyme-linked immunosorbent assay with basal glycemia, glycosylated hemoglobin, blood pressure, endothelial dysfunction (assessed by pressure wave velocity), hypertensive retinopathy (by Keith-Wagener classification), left ventricular hypertrophy (by Cornell and Sokolow indexes), cardiovascular risk and target organ  damage.There are significant correlations between endoglin and glycemia, systolic blood pressure, pulse pressure, pressure wave velocity and electrocardiographically assessed left ventricular hypertrophy. Endoglin levels were significantly higher in patients with diabetes who had nondipper and extreme dipper circadian blood pressure patterns than in dipper circadian patterns, in patients with hypertension and diabetes who had riser pattern than in the other patients, and in patients with diabetes but not hypertension who had extreme dipper pattern than in dipper, nondipper and riser groups. There was also a significant correlation between plasma-soluble endoglin and lower levels of systolic night-day ratio. Higher endoglin levels were found in patients with diabetes who had retinopathy, in patients with diabetes who had a high probability of 10-year cardiovascular risk, and in patients with diabetes and hypertension who had three or more damaged target organs  than in those with no organs affected.This study shows that endoglin is an indicator of hypertension- and diabetes-associated vascular pathologies as endothelial dysfunction and cardiovascular damage. In typery state . The funry state . Hyperglry state .Endoglin , a type I transmembrane glycoprotein highly expressed on proliferating vascular endothelial cells (ECs) , has beeEndoglin is expressed at low levels in resting ECs, but it is highly expressed in vascular ECs during embryogenesis , in inflIn vitro studies have demonstrated that Sol-endoglin impairs EC proliferation and capillary formation [A soluble form of endoglin (Sol-endoglin) has been detected in plasma, serum and urine from patients with pathologies such as preeclampsia and cancer, and its peptide sequence suggests that it is an N-terminal cleavage product of full-length, membrane-bound endoglin . Uterineormation . Sol-endormation . Thus, SWe have assessed the relationship between plasma levels of Sol-endoglin and vascular alterations associated with diabetes, specifically blood pressure, endothelial dysfunction, retinopathy, degree of left ventricular hypertrophy, cardiovascular risk and target organ damage in patients with type 2 diabetes and hypertension compared to control patients of similar age.This is a cross-sectional study performed in patients with diabetes with or without hypertension. Patients enrolled in the study over a period of 24 months (from January 2008 to January 2010) were from the Internal Medicine Section, University Hospital of Salamanca, and from the Primary Care Research Unit of La Alamedilla Health Centre , Salamanca, Spain, which covers a population of 46,000 inhabitants. Altogether, 288 consecutive patients complied with the inclusion or exclusion criteria and were asked to participate in the study. Groups of patients were as follows: 64 patients with diabetes (42 of them were hypertensive) and 159 patients with hypertension but not diabetes. Sixty-five healthy individuals were selected as a control group.Inclusion criteria were patients diagnosed with diabetes mellitus 2 and/or hypertension and aged 20-80 years, with none of the following exclusion criteria: patients unable to comply with the protocol requirements , patients participating or who were going to participate in a clinical trial during the study, and patients with serious comorbidities representing a threat to life. Most of the patients with hypertension and diabetes received drug therapy (except those controlled by diet), which is described in Table Hypertension was diagnosed when the mean of three separate measurements of blood pressure over time was ≥ 140 mmHg for systolic blood pressure (SBP) and/or ≥ 90 mmHg for diastolic blood pressure (DBP). At each measurement, blood pressure was measured at least twice, separated by more than 1 minute, as recommended by The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension and of the European Society of Cardiology . DiabeteThe experimental protocol was in accordance with the Declaration of Helsinki (2000) of the World Medical Association and also was in agreement with the guidelines of and approved by the Ethics Committee of the University Hospital of Salamanca, Spain, and complied with Spanish data protection law 15/1999 and its developed specifications (RD 1720/2007). Each patient included in the study signed an informed consent form to participate in the study after full explanation of the purpose and nature of all procedures used. To guarantee data confidentiality, all the electronic and paper copies of the protocol, signed informed consent documents and results of the tests were kept locked in a safe place, and only the study investigators had access to the data on the people who agreed to participate in the study.We evaluated the next sociodemographic variables and cardiovascular risk factors: patient age and sex, hypertension, dyslipidemia, alcohol consumption, smoking, physical activity and history of premature cardiovascular disease  in first-degree relatives, myocardial infarction, angina, revascularization, heart failure, atrial fibrillation and cerebrovascular events , as well as the presence of symptomatic peripheral arterial disease.Body weight was determined at two different times using a homologated electronic scale  following due calibration (precision ± 0.1 kg), with the patient wearing light clothing and without shoes. Readings were rounded to 100 g. Height was measured with a portable system (Seca 222), recording the average of two readings, and with the patient shoeless in the standing position. The values were rounded to the closest centimeter. Body mass index  was also calculated. Waist circumference was measured using a flexible, graduated measuring tape with the patient in the standing position without clothing. The upper border of the iliac crests was located, and the tape was wrapped just above this point without compressing the skin. The reading was taken at the end of a normal breath according to the recommendations of the 2007 SEEDO Conference .Blood samples were collected in the morning, after the patient had fasted for at least 8 hours prior to other measurements. Physiological determinations were creatinine, basal glucose and glycosylated hemoglobin (HbA1c), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol and triglycerides in blood and microalbuminuria. The parameters were measured on a blind basis in a General Hospital Biochemistry laboratory using standard authomatized techniques.Office blood pressure evaluation involved three measurements of SBP and DBP using the average of the last two measurements, with a validated OMRON model M7 sphygmomanometer , following the recommendations of the European Society of Hypertension . Pulse pHome blood pressure was self-measured using an OMROM model M7 sphygmomanometer as previously described . PatientAmbulatory blood pressure monitoring was performed on a standard activity day, with a SpaceLabs 90207 model , validated according to the protocol of the British Hypertension Society . RecordsPeripheral artery disease (PAD) was evaluated in the morning using the ankle-brachial index (ABI), with the patient having refrained from consuming caffeine-containing beverages and alcohol, and not having smoked, in the previous 12 h, and with room temperature ranging between 22°C and 24°C. With the feet uncovered and in a supine decubitus position after resting for 20 min, pressure in the lower extremities was measured using a portable Doppler system Minidop Es-100Vx  applying the probe at the anterior or posterior tibial artery at an angle of approximately 60° to blood flow direction. Blood pressure was also measured twice at 3- to 5-minute intervals in both arms. ABI was calculated as previously described . SubclinElectrocardiographic (ECG) examination was performed with a General Electric MAC 3.500 ECG System , which measures voltage and duration of waves and estimates the criteria of the Cornell voltage duration product (Cornell VDP)  to assesKidney damage was assessed by measuring plasma creatinine concentrations, glomerular filtration rate was estimated by CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)  and the Retinography was performed with a Topcon TRC NW 200 nonmydriatic retinal camera , obtaining images centered on the papilla. Captured images were classified by two independent observers according to the Keith-Wagener classification for hypertensive retinopathy . RetinopPulse wave velocity (PWV) was calculated in the morning (between 8:30 and 11:00 AM) 1-2 days before blood was drawn, using the SphygmoCor System  with patients in supine decubitus position . This anPulse wave analysis was performed with a sensor in the radial artery using mathematical transformations to estimate the aortic pulse wave with the SphygmoCor system , with patients in sitting position and resting the arm on a rigid surface. The aortic wave morphology was used to estimate central (aortic) arterial pressure along with central ventricular load, diastolic perfusion pressure, subendocardial viability index, pressure increment, central pulse pressure and the augmentation index (PWA), defined as the percentage of the increase in central pulse pressure: AIx = pressure increase × 100/pulse pressure .Cardiovascular risk of patients was assessed using the scale of the ESH-ESC guide 2007 . Risk caSol-endoglin concentration in plasma samples was evaluated using an enzyme-linked immunosorbent assay method  following the instructions of the manufacturer. With regard to specificity, the assay recognizes recombinant and human endoglin without significant cross-reactivity or interference with other members of the TGF-β family. With regard to sensitivity, the minimum detectable dose ranged from 0.001 to 0.030 ng/mL. Absorbance  was determined using a spectrophotometer  at 450 nm with a wavelength correction of 540 nm.2 test was used to analyze associations between qualitative variables. Student's t-test was used for independent samples to compare quantitative variables for two groups, and one-way analysis of variance was used for more than two groups. Pearson's correlation test was used to analyze associations between quantitative variables. A P value lower than 0.05 was considered statistically significant. Owing to our sample size (288 patients), our low variability and the selected α value (0.05), the power of our study is 0.95 .Data input was performed using the Teleform system  and exporting the data to the PASW version 18.0 statistical package  for data analysis. Data followed a normal distribution as confirmed by kurtosis normality of residuals test. Data were presented as means ± standard error of the mean (SEM) or standard deviation in the case of quantitative variables, and as frequency distributions for qualitative variables. The χ2) and 32.13% of patients were obese (BMI > 30 kg/m2)  in patients with diabetes and hypertension and in all patients with hypertension with or without diabetes Table . There wEndothelial dysfunction was evaluated by the analysis of PWV, which indicates arterial stiffness. Our study show that plasma Sol-endoglin levels showed a positive correlation with PWV values in patients with hypertension and diabetes Table .We found a strong relation between Sol-endoglin plasma levels and retinopathy. Higher endoglin levels (above 5 ng/mL) were found in all patients with diabetes  and in patients with hypertension and diabetes  categorized as grade III and grade IV in the Keith-Wagener retinal changes classification, in both right and left eyes compared with patients with grades I and II , and this is especially important as heart rate has been recently suggested to be a marker of increased vascular risk [Our data shows that Sol-endoglin plasma levels are significantly related to glycemia, SBP, pulse pressure, PWV, heart rate and the degree of LVH assessed by ECG. Sol-endoglin plasma levels are different in patient groups depending on the circadian blood pressure pattern, and increased endoglin levels are associated with retinopathy, very high 10-year cardiovascular risk and increased number of damaged target organs in patients with type 2 diabetes. This is the first study in humans showing that plasma Sol-endoglin concentration could serve as an indicator of diabetes-associated pathologies such as hypertension, endothelial dysfunction and cardiovascular risk. It should be noted that a high correlation coefficient has been obtained between plasma Sol-endoglin levels and heart rate  show a defective vasodilator response to endothelium-dependent vasodilator substances such as acetylcholine or bradykinin [+/- engmice show a decreased NO synthesis and a decreased eNOS expression [+/- engmice, suggesting the involvement of endoglin in the TGF-β-regulated vascular homeostasis [As previously described, the impairment of endothelium-dependent vasodilation in patients with diabetes is due to the impaired NO bioavailability , and endadykinin . In agrepression ,49,51. Teostasis .Changes in Sol-endoglin plasma levels have been reported in other pathologies different from preeclampsia, such as atherosclerosis and coronary artery disease . Also, cLimitations of our study are its cross-sectional design, which precludes longitudinal analysis between endoglin, cardiovascular risk factors and subclinical organ damage, and the selection of the study population, since sampling was performed consecutively with pragmatic and broad inclusion criteria, including patients with hypertension with a recent diagnosis or short course of hypertension, patients with diabetes and hyperlipidemia, and many patients receiving drug therapy. This could modify blood pressure levels and therefore limit the validity of some results. Consequently, the heterogeneity of the sample could lead to some limitations when interpreting the results, though it is quite similar to the distribution of the real population of short-course patients with hypertension who have some risk factors and without previous cardiovascular disease.Endoglin expression has revealed its prognostic and diagnostic value in other circumstances, being a potential vascular target for antiangiogenic cancer therapy . Our stuThe authors declare that they have no competing interests associated with this paper.AMB-M performed the plasma Sol-endoglin determinations and statistical analyses and contributed to the manuscript writing. LG-O, MAG-M, JIR-R and AS-R were responsible for the recruitment of patients, acquisition of patients' biological samples and data. LGO, MAG-M and JMLN made substantial contributions to the conception and design of the study and were involved in drafting the protocol, the interpretation of data and the preparation of the manuscript. CM-S was responsible for the integrity of the work as a whole, from inception to the published article. All authors read and approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/8/86/prepub


The reduction in renal function secondary to immunologic and non-immunologic CAN leads to several complications, including anemia and calcium-phosphorus metabolism imbalance and may be associated to worsening Health-Related Quality of Life. We sought to evaluate the relationship between kidney function and Euro-Qol 5 Dimension Index .This study is a secondary analysis of existing data gathered from two cross-sectional studies. We enrolled 233 and 209 subjects aged 18–74 years who received a kidney transplant in US and UK respectively. For the present analysis we excluded recipients with multiple or multi-organ transplantation, creatinine kinase ≥200 U/L, acute renal failure, and without creatinine assessments in 3 months pre-enrollment leaving 281 subjects overall. The questionnaires were administered independently in the two centers. Both packets included the EQ-5Dindex in both samples . The mean adjusted disutility associated to CKD stage 5 compared to CKD stage 1–2 was Δ= −0.38 in the UK sample, Δ= −0.11 in the US sample and Δ= −0.22 in the whole sample. The adjusted median disutility associated to CKD stage 5 compared to CKD stage 1–2 for the whole sample was 0.18 . Center effect was not statistically significant.CKD severity was negatively associated with EQ-5DImpaired renal function is associated with reduced health-related quality of life independent of possible confounders, center-effect and analytic framework. Kidney transplantation (KTX) is the treatment of choice in End Stage Renal Disease. In the EU and the US the number of transplantations performed increased in the last 15 years but waiting lists for transplantation continue to grow because demand exceeds organ supply . Graft sWe have recently shown that impaired renal function is associated with reduced health-related quality of life in North-American kidney transplant recipients . HoweverData was obtained from KTX patients enrolled at the kidney transplant facilities of the Renal Unit at the Cardiff and Wales NHS Trust in Cardiff, UK (n=209) and Saint Louis University Hospital, St. Louis, MO (n=233);Patients were identified from the renal departmental database of the Saint Louis University Hospital from January 2008 to June 2008. All adult patients (18–74 years old) with a documented kidney transplantation were asked to answer a self-administered questionnaire during a regular visit at the transplant clinic (n=282). Patients providing informed consent were 233 . We excluded patients with multi-organ or multiple transplant, and those with no serum creatinine measurements in the 3 months prior to the interview. Since severe acute health events may affect quality of life and determine transient variation in Glomerular Filtration Rate (GFR) we also excluded patients who underwent major surgery in the months prior to enrollment and those with markers of acute cellular damage (Creatine-Kinase > 200 U/L). The final sample resulted in 137 patients. Information including biochemistry assessments results obtained in the 3 months prior to interview and lifetime medical history was abstracted from clinical charts, transplant coordinators records and electronic medical records. We evaluated the accuracy of data reporting across the 3 different sources by evaluating the agreement of laboratory test results performed on the same date for each subject. Since the agreement was almost perfect  we merged the information into one common clinical database in order to maximize data completeness. The Saint Louis University Institutional Review Board approved the study protocol.All patients registered in the renal departmental database of the Cardiff and Vale NHS Trust in September 2002 (n=1251) were asked to answer a self-administered questionnaire. Of them 157 were on Continuous Ambulatory Peritonale Dialysis, 268 were on hemodialysis, 115 were on CKD pre-dialysis stage, and 711 received a transplantation. All patients treated at the renal clinic received a postal-survey at their home while those on chronic dialysis at the time of survey were asked to complete the questionnaire during a regular dialysis session . . Patients providing the informed consent were 33.3% of the original sample . For the present analysis we included all adult patients with a documented kidney transplant who completed the survey questionnaire . and had at least one serum creatinine measurement in the 3 months prior to the interview (n=144). No patient with markers of acute cellular damage in the 3 months prior to survey return date were identified (Creatine-Kinase > 200 U/L). Clinical data including serum creatinine concentrations and medical history were abstracted from the clinical database of the Cardiff and Vale NHS Trust.index). Its classification system consists of 5 attributes  defining unique 5-digit health state vectors ranging from 11111 for perfect health to 33333 for the worst possible state of health [index score for the US sample [Our outcome measure was the Euro-QOL 5-Dimension Index , Aspartate Transaminase (AST), creatine kinase, glucose, phosphorus and calcium). We estimated Glomerular Filtration Rate (GFR) with the MDRD equation (4-variable) . We clasDescriptive statistics were calculated and reported as mean ± standard deviation (or median with interquartile range) for continuous variables and frequency for categorical variables. Differences in socio-demographic and clinical characteristics across CKD stages were tested by χ2 for categorical variables and Analysis of Variance  for continuous variables. We evaluated the unadjusted associations between CKD severity, glucose, AST, hemoglobin, phosphorus, calcium, and Albumin serum concentrations with Spearman’s correlation coefficient. Spearman's correlation was also used to test unadjusted associations between eGFR (or CKD stages) and quality of life.index scores were strongly skewed and OLS regression assumptions were not satisfied, we identified the power transformation maximizing model R2 with the SAS Proc Transform routine:Ordinary Least Square (OLS) models are traditionally adopted to analyze quality of life data. Under ideal conditions they have attractive properties: the conditional mean is an easy-to-interpret, parsimonious representation of the relationship between a continuous outcome and a predictor variable. Additionally, economic models used in cost-effectiveness analysis adopt adjusted means from OLS models in Quality-Adjusted Life Years (QALY) calculation. For this reason we initially used general linear models to obtain adjusted association estimates. Since EQ-5DQL is the transformed dependent variable of the general linear model and QOL is the raw health utility score.where We specified 2 consecutive steps for the GLM analyses. In the first step we included renal function alone to assess the unadjusted coefficients of association. Variables included in the second step were age, gender, ethnicity, months since transplant, diagnosis of diabetes, hypertension, cardiovascular diseases, anxiety/depression, ALT, AST, glucose levels and center of enrollment. From the second step, we obtained adjusted means for each CKD category (as defined above). Results were back-transformed into the original scale, correcting for back-transformation bias . Signifiindex score was strongly skewed and a relevant ceiling effect was observed, we used Quantile Regression to evaluate the consistency of the association between renal impairment and HRQOL at the 15th, 30th, 50th, 70th and 85th quantile of the outcome distribution [2 change in eGFR.Since the distribution of the EQ-5Dribution  Quantileribution , for theBlood concentrations of Hemoglobin, Albumin, Calcium and Phosphorus were not considered as confounders in the statistical models since they may be part of the causal pathway linking CKD severity and HRQOL. In order to evaluate whether the association between eGFR and HRQOL was partially independent from the hypothesized mediators we included those variables to the statistical models in a secondary analysis.P values < 0.05 as statistically significant and p<0.10 as marginally significant. We used SAS 9.2® to conduct all the analyses.We considered For the main outcome (mean EQ-5D index utility estimate), the pooled sample size would achieve ~80% power of detecting a small effect size of 0.23 in a ANOVA test of 4 groups of similar size. This effect size corresponds to a 0.04 difference across CKD classes, a difference considered clinically significant ,23-25.Demographic and clinical characteristics of study sample are summarized in Table index scores in the two samples were 0.73  and 0.83 . CKD severity was associated to EQ-5Dindex score in both samples . The mean unadjusted disutility associated to CKD stage 5 compared to CKD stage 1–2 was Δ= −0.22 (p<0.01) in the pooled sample, Δ= −0.25 in the UK sample (p=0.01) and Δ= −0.09 (p=0.04) in the US sample .The median EQ-5Dindex across CKD stages evaluated with Spearman’s partial correlation was ρ= −0.18  , ρ= −0.20  , ρ= −0.18  after adjustment for age, gender, center of enrollment, diabetes, cardiovascular diseases, anxiety or depression, hypertension, ALT, AST, months since transplant. The mean adjusted disutility associated to CKD stage 5 compared to CKD stage 1–2 was Δ= −0.38 in the UK sample and Δ= −0.11 in the US sample  to 0.06 (τ=0.85) and were not significant at τ<0.30 .According with previous findings ,26, we oWe have found no evidence of a moderating center effect on the relationship between HRQOL and CKD severity in both OLS and Quantile regression framework. However the difference across centers in the estimated disutility associated to CKD stage 5 compared to CKD stage 1–2 was large and clinically significant according to proposed thresholds defining minimal clinically important difference ,23-25 anIt is worth noticing that the difference observed across CKD classes is clinically significant in both samples ,23-25: tth and the 85th percentile of the outcome distribution exceeds the suggested threshold for clinical significance in utility scores, thus indicating that patients with otherwise better conditions suffer a bigger utility penalty form reduced renal function than patient with worse general health conditions. As a consequence our results suggest that unobserved factors might moderate the association of renal function and HRQOL. Several factors has been shown to moderate the relationship between health status and QOL including income [Finally, we used quantile regression to evaluate the consistency of the association between renal impairment and HRQOL at the 15th, 30th, 50th, 70th and 85th quantile of the outcome distribution and to corroborate results from OLS regression. Even though statistically significant, median regression, which is equivalent to a quantile regression estimated for τ=0.50, yielded somewhat smaller disutility estimates compared to general linear models (ordinary least square). The quantile process estimated entering eGFR as a continuous variable indicate that the relationship between eGFR and HRQOL was slightly stronger in the upper tail of the outcome distribution. The difference in CKD-related disutility between the 15g income , social g income , personag income  and contThe strengths of the present study are: i) our data expands the current knowledge on cross-national HRQOL studies; ii) we adjusted for several known correlates of HRQOL in multivariable regression ; iii) we used multiple serum creatinine assessments collected in the 3 month period prior to enrollment to define study groups in order to minimize classification bias; iv) we confirmed the consistency of our results under different analytic frameworks. However, our study presents some limitations. First, we lacked information on possibly important confounders such as type of transplant (i.e. living/deceased donor), immunosuppression regimen, patients’ personality traits. As a consequence residual confounding cannot be ruled out as an alternative explanation of our results. One additional limitation of this study is its correlational design. Additionally data collection was differently performed in the US and UK studies, which may partially bias our cross-national comparison. Further, only a small fraction of UK eligible patients responded to the questionnaire leaving a potential for selection bias possibly limiting the generalizability of our results: our sample had poorer renal function and were more likely to have hypertension and diabetes compared to the general KTX population in UK ,32. Finaindex scores observed under OLS analytic framework and suggests that unobserved factors might moderate this association. Further studies specifically designed to characterize such moderating factors might help identify patients more likely to benefit from kidney function preserving strategies. The present analysis provides further evidence supporting efforts in preserving renal function after kidney transplantation.In the present cross-national cross-sectional study, we observed that a decline in kidney function was associated with worsening health utility estimates following kidney transplantation. This association was robust for adjustment for several established correlates of HRQOL and was confirmed in both UK & US centers. Even though the center effect was not statistically significant, the magnitude of the difference in health disutilities observed in the two centers merits further evaluation. Results from quantile regression confirmed the validity of the association between eGFR and EQ-5DLN and PME received consulting fees from BMS pharmaceuticals. KS is employed at BMS pharmaceuticals. KB has no competing interests.Study design: LN and PME. Data Analysis: LN. Interpretation of results: LN, PME, KS, KB. First draft: LN. Revision and Final draft: LN, PME, KS, KB. All authors read and approved the final manuscript


Mitochondrial dysfunction is implicated in many cardiovascular diseases, including hypertension, and may be associated with an overactive renin-angiotensin system (RAS). Angiotensin (Ang) II, a potent vasoconstrictor hormone of the RAS, also impairs baroreflex and mitochondrial function. Most deleterious cardiovascular actions of Ang II are thought to be mediated by NADPH-oxidase- (NOX-) derived reactive oxygen species (ROS) that may also stimulate mitochondrial oxidant release and alter redox-sensitive signaling pathways in the brain. Within the RAS, the actions of Ang II are counterbalanced by Ang-(1–7), a vasodilatory peptide known to mitigate against increased oxidant stress. A balance between Ang II and Ang-(1–7) within the brain dorsal medulla contributes to maintenance of normal blood pressure and proper functioning of the arterial baroreceptor reflex for control of heart rate. We propose that Ang-(1–7) may negatively regulate the redox signaling pathways activated by Ang II to maintain normal blood pressure, baroreflex, and mitochondrial function through attenuating ROS . The renin-angiotensin system (RAS), and in particular angiotensin (Ang) II, is implicated in the impairment of arterial baroreflex function and reduction of heart rate variability (HRV) commonly associated with hypertension –4. HowevOveractivation of the RAS in pathological conditions, such as hypertension, results in excessive ROS production through the prooxidant actions of Ang II , 25. TheAng-(1–7) has emerged as a major counter-regulatory peptide to Ang II actions and may serve to inhibit Ang II-stimulated ROS production through inhibiting NOX and/or increased ROS scavenging by augmenting antioxidant enzymes such as catalase , 39. Ind1 receptor antagonist, candesartan, which normalized blood pressure but did not significantly improve the vagal indices of BRS or HRV. We have yet to determine the effect of these treatments on mitochondrial ROS, but neither treatment altered cytoplasmic NOX activity. Central infusion of the ROS scavenger tempol did not lower blood pressure or influence indices of baroreflex function, but significantly reduced cytoplasmic NOX activity, suggesting independence from ROS-related mechanisms for blood pressure lowering and autonomic nervous system balance in the hypertensive (mRen2)27 strain. However, we do not know whether tempol efficiently targets mitochondrial ROS or the extent that alterations in mitochondrial ROS would influence blood pressure and/or BRS in the transgenic rats. Dikalova and colleagues have reported blood pressure lowering effects of Mito-TEMPO in both Ang II-induced and DOCA salt hypertension in mice while a similar dose of tempol alone did not lower blood pressure in this study  supportapparent . While aapparent , the lacapparent . An interesting paradox to the beneficial role of these regulatory phosphates is that both MKP-1 and PTP1b have negative effects on metabolic function , 58. In α and β1 subunits, Figures Altered mitochondrial oxidant and/or energy levels are associated with a stimulated AMP-activated protein kinase (AMPK) pathway that is activated in response to depleted cellular energy levels, to restore mitochondrial biogenesis and ATP levels , 66. AMPMitochondria-derived ROS which often accompanies impaired autonomic function is an emerging therapeutic target in hypertension , 45–47.


TCCO2) with regard to arterial carbon dioxide partial pressure (PaCO2) in severe obese patients undergoing laparoscopic bariatric surgery. Twenty-one patients with BMI>35 kg/m2 were enrolled in our study. Their PaCO2, end-tidal carbon dioxide partial pressure (PetCO2), as well as PTCCO2 values were measured at before pneumoperitoneum and 30 min, 60 min, 120 min after pneumoperitoneum respectively. Then the differences between each pair of values (PetCO2–PaCO2) and. (PTCCO2–PaCO2) were calculated. Bland–Altman method, correlation and regression analysis, as well as exact probability method and two way contingency table were employed for the data analysis. 21 adults  were finally included in this study. One patient was eliminated due to the use of vaso-excitor material phenylephrine during anesthesia induction. Eighty-four sample sets were obtained. The average PaCO2–PTCCO2 difference was 0.9±1.3 mmHg (mean±SD). And the average PaCO2–PetCO2 difference was 10.3±2.3 mmHg (mean±SD). The linear regression equation of PaCO2–PetCO2 is PetCO2 = 11.58+0.57×PaCO2 , whereas the one of PaCO2–PTCCO2 is PTCCO2 = 0.60+0.97×PaCO2 (r2 = 0.89). The LOA (limits of agreement) of 95% average PaCO2–PetCO2 difference is 10.3±4.6 mmHg (mean±1.96 SD), while the LOA of 95% average PaCO2–PTCCO2 difference is 0.9±2.6 mmHg (mean±1.96 SD). In conclusion, transcutaneous carbon dioxide monitoring provides a better estimate of PaCO2 than PetCO2 in severe obese patients undergoing laparoscopic bariatric surgery.To investigate the correlation and accuracy of transcutaneous carbon dioxide partial pressure (P The end-tidal carbon dioxide partial pressure (PetCO2) measurement has been widely used for the continuous noninvasive monitoring of carbon dioxide in patients with tracheal intubation during general anesthesia, However, many factors may possibly affect the accuracy of PetCO2 monitoring, such as mismatch of ventilation to blood flow (V/Q ratio), chronic obstructive pulmonary disease, obstructive sleep apnea syndrome, surgery postures, smoking, ect. Recently, noninvasive transcutaneous carbon dioxide partial pressure (PTCCO2) monitoring has been used in infants and in adult patients with good accuracy Currently the “gold standard” technique for the measurement of arterial carbon dioxide partial pressure , fentanyl (2–4 μg.kg −1), and rocuronium (0.6 mg.kg−1) by the same anesthetist. After tracheal intubation, patients were ventilated with 100% oxygen (2 L/min) under the mode of intermittent positive pressure ventilation (IPPV), with a tidal volume of 6–10 ml/kg and an I:E ratio of 1∶2. The ventilatory frequency and tidal volume were adjusted to maintain normocarbia . The PetCO2 was monitored by side stream spirpometry . PTCCO2 was monitored with a TCM-4 device . One of the authors calibrated, placed, and maintained the monitor. Before placement, the electrode was cleaned, a new membrane applied, and calibration done according to the manufacturer’s recommendations. The working temperature of the electrode was set at 44°C and the electrode was placed on the chest. The area where the electrode was placed was swabbed with alcohol in order to to facilitate adhesion of the disk to the skin. Re-calibration was required once the position of the electrode was changed. The electrode was removed, adjusted, and replaced in a different location on the chest every 2 h to avoid thermal injury.Anesthesia was induced with propofol , remifentanil (0.1–0.2 μg kg−1.min−1), and atracurium (0.6 mg. kg−1.h−1) to keep the variation of blood pressure and HR within 20% of baseline values. Those patients whose blood pressure drop was more than 20% baseline value or who needed a vasoconstrictor to maintain hemodynamics stable were excluded from the study. yet the data from them before hypotension occurred could still be used for the analysis. The patient’s body temperature was continuously monitored nasopharyngeally and maintained at 36°C to 37°C. The room temperature was maintained at 23°C to 25°C. Pneumoperitoneum was established and intraperitoneal CO2 infusion pressure was maintained at 12–14 mmHg during the surgery.An AS/5 monitor  was employed to monitor the patients’ electrocardiography, pulse oxymetry, and noninvasive blood pressure. Before anesthesia, patients’ heart rate (HR) and arterial blood pressure were both recorded as baseline. A 20-G or 22-G arterial catheter was inserted into the left radial artery under local anesthesia for ABG sampling. PaCO2 and PTCCO2 or PaCO2 and PetCO2 using Bland–Altman method. Pearson correlation coefficient and linear regression analysis were used to establish the relationship. The exact probability method and two way contingency table were employed to compare the difference of 5 mmHg or less and 3 mmHg or less between PaCO2 and the other two noninvasive variables. A P value of 0.05 or less was considered statistically significant.Data were presented as mean±SD. Statistical analysis was performed by SPSS version 17.0.We assessed the agreement between P2, 42.1(5.4) kg/m2) were recruited into this study. All patients underwent laparoscopic bariatric surgery. The PaCO2, PetCO2, and PTCCO2 values were recorded at 4 time points. Eight-four samples were finally obtained. The mean values of these variables at different time points are presented in TCCO2 was correlated with PaCO2 at each time point . PetCO2 was correlated with PaCO2 at each time point . The PaCO2 values were ranging from 42.2 to 58.4 mmHg. The average PaCO2–PetCO2 difference was 10.3±2.3 mmHg and the average PaCO2–PTCCO2 difference was 0.9±1.3 mmHg. In those samples, both PetCO2 and PTCCO2 were closely correlated with PaCO2. The linear regression equation between PetCO2 and PaCO2 was PetCO2 = 11.58+0.57×PaCO2, r2 = 0.64, P<0.01. Only one PetCO2–PaCO2 difference  was 5 mmHg or less while all values of PTCCO2–PaCO2 difference  were 5 mmHg or less (P<0.01). According to Bland-Altman analysis, the 95% limits of agreement (LOA) of the average PaCO2–PetCO2 difference was 10.3±4.6 mmHg yr; weight from 86 to 160 kg, 119.3(22.1)kg; BMI from 35.3 to 51.1 kg/m4, P<0.01; and PTC9, P<0.01. In all etCO2) measurement has been widely used in the anesthetic management. However, quite a number of factors may possibly affect the accuracy of PetCO2 measurement, including alveolar ventilation volume, V/Q ratio, chronic obstructive pulmonary disease, etc. Due to the effects of weight loss, remission of diabetes mellitus and improvement of health-related quality, bariatric surgery gets rapid development in clinical practice 2 pneumoperitoneum results in the further decrease of FRC and greater degree of intrapulmonary shunt, which diminishes the accuracy of PetCO2. Nevertheless, PTCCO2 monitoring uses heated electrodes to improve local perfusion , which facilitates the absorption of carbon dioxide into the heated electrodes via skin diffusion. The carbon dioxide inside the electrodes changes the internal pH value, which results in PTCCO2 signals. Reid CW et al aCO2–PetCO2 difference increased along with PaCO2 levels. In the patients undergoing bariatric surgery the PetCO2 is usually greater than 40 mmHg, and PaCO2 may be underestimated, while the PTCCO2 is still accurately reflect the PaCO2 levels. Especially after the extubation, PetCO2 monitor becomes unavailable. And it is highly likely that hypoxia and hypercapnia happens. PTCCO2 monitoring is particularly valuable. In our study, the average PaCO2–PetCO2 difference was 10.3±2.3 mmHg whereas the average PaCO2–PTCCO2 difference was 0.9±1.3 mmHg. Those findings are unanimous with the past study.The end-tidal carbon dioxide .Previous studies reported that the COTCCO2 was more accurate in patients with a BMI greater than 40 kg/m2 undergoing transabdominal bariatric surgery. Maniscalco M et al 2) with chronic obstructive pulmonary disease (COPD), obstructive sleep apnea syndrome (OSAS), hypopnea syndrome (OHS) and respiratory failure (RF), PTCCO2 still accurately reflected the PaCO2,compared with the blood gas analysis. Our findings indicated that PTCCO2 was more accurate in reflecting the real levels of PaCO2 than PetCO2 in patients with BMI>35 kg/m2 undergoing laparoscopic bariatric surgery. And only one PetCO2 readings was 5 mmHg or less from PaCO2 while all values of PTCCO2 were 5 mmHg or less.Griffin J et al TCCO2 monitoring depends on monitor and a series of patient factors. Although TC-CO2 monitoring more accurately reflected PaCO2 in most of the patients in the previous studies, several technical factors may affect the accuracy of monitor, including trapped air bubbles, improper placement, damaged membranes, and inappropriate calibration techniques. Patient-related factors may also affect the accuracy, such as variations in skin thickness, the presence of edema, tissue hypoperfusion, or the use of vasoconstricting drugs and oxygen deficiency acidosis. Nishiyama T et al TCCO2 and PTCO2 more precisely predict the PaCO2 and PaO2 when the electrodes were put on the chest, compared to the placement at the upper arm and forearm. Nishiyama T etc The successful PTCCO2 and PTCO2 could accurately estimate PaCO2 and PaO2 respectively. Sorensen LC et al Electrode heating temperature can significantly affect the accuracy of the measurement results. Nishiyama T et al TCCO2 monitoring. Lower environmental temperature resulted in skin vascular contraction, reduced blood flow, In this study temperature in the operating room always maintained above 23°C. Meanwhile, patients’ exposure was reduced to the lowest possible level. Currently there are still disputes about the accuracy of PTCCO2 monitoring with the use of vasopressors, and past studies suggested vasopressors affected accuracy of PTCCO2 monitoring TCCO2 monitoring. Most of general anesthetics have the effect of vasodilation. Propofol administration produced venodilation and peripheral vasodilation in humans Skin tissue perfusion also affected the accuracy of the PetCO2 may underestimate PaCO2 because of inadequate washout of the anatomical dead space by a small tidal volume and the relatively slow response time of infrared CO2 analyzers. Especially during use of high frequency jet ventilation (HFJV) aCO2 in situations where continuous and precise control of CO2 levels in perioperative with HFJV TCCO2 monitoring especially useful during use of HFJV in obese patients which can avoid them in high risks of hypercapnia.We all know that during jet ventilation (JV), PTCCO2 can not substitute the PetCO2 monitoring completely as PetCO2 monitoring has many unique advantages, including the judgment of successful intubation, the warning of breathing circuit disconnected and indicator of pulmonary embolism, etc. In addition, the PetCO2 wave pattern had more clinical significance. The PTCCO2 monitoring was limited by many factors, including longer priming time, adjuscting before use, periodically electrode replacement, no CO2 waveform and the risk of skin burn injury However, PTCCO2 can estimate the PaCO2 more accurately than PetCO2 in obese patients under laparoscopic bariatric surgery. Moreover, the application of PTCCO2 monitoring might improve the quality of the anesthesia management.In conclusion, our study demonstrated that P