Several studies have shown that cocoa and cocoa-containing foods have the potential to lower blood pressure and improve endothelial function. Most of the studies reporting the beneficial effects of dark chocolate on blood pressure have been short (≤ 4 weeks). The aim of the present 8-wks (weeks) study was to assess the effects of regular consumption of dark chocolate during a reduced snack consumption intervention on blood pressure and other cardiovascular risk factors in mildly hypertensive individuals.2 with mild hypertension. During the intervention period (8-wks) the participants reduced the intake of habitual snacks and replaced them with dark chocolate (49 g/day). In the control period, they only reduced the snacks without any added chocolate. Data  was collected in the beginning and end of both periods (intervention and control), and some variables also in the run-in and run-out periods .This was a randomized, controlled, cross-over trial involving 22 adults , aged 33–64 y, BMI 27.7 ± 3.7 kg/mDaily consumption of dark chocolate had no effects on 24 h blood pressure, resting blood pressure  or arterial stiffness .Weight was reduced by 1.0 ± 2.2 kg during the control (reduced snack only) period, but was unchanged while eating chocolate (p < 0.027 between the treatments).The data collected in this study indicates that inclusion of dark chocolate daily in the diet had no significant effects on blood pressure or other cardiovascular risk factors during a reduced snack period.NCT02130141ClinicalTrials.gov identifier  Polyphenols are plant-derived compounds; secondary metabolites with an essential role in protection of plants against different environmental and microbial threats . PolypheUnlike vitamins, polyphenols are not essential nutrients. However, regular intake of polyphenols may have favorable effects on health and risk of chronic diseases. Also, several clinical trials have shown a favorable effect of flavonoids on cardiovascular disease (CVD) risk factors , 3. The Cocoa and cocoa-containing foods, such as dark chocolate, represent a very rich source of flavonoids as they provide a higher content of flavonoids per serving than red wine or tea . Cocoa cThe beneficial health effects of cocoa have been especially related to endothelial function . ConsumpMost of the studies reporting the beneficial effects of dark chocolate on blood pressure have been short  and the daily dose substantial, as much as 100 g/day –18. Ther2. Exclusion criteria were smoking and regular use of medications for cardiovascular disease, diabetes or asthma. Twenty two participants (14 men and 8 women), 33–64 years old, mean age 45.8 (SD 8.3) years with a BMI of 27.9 (SD 3.6) kg/m2 completed the study and were included in the final analysis. Eight participants withdrew during the study for personal reasons or because their blood pressure exceeded the accepted level (159/99 mmHg). Written informed consent was obtained from all participants. The study protocol was reviewed by the Ethics Committee of the Helsinki and Uusimaa Hospital District, Finland. The study was registered at the US National Institutes of Health clinical trials database , identifier NCT02130141.Thirty healthy volunteers  were recruited by flyers and newspaper advertisements. To be included into the study, the participants had to have mild hypertension (140–159 mmHg systolic blood pressure (SBP) or 90–99 mmHg diastolic blood pressure (DBP) according to the Finnish Hypertension Society) and BMI < 35 kg/mThe study was a randomized, controlled, 8-wks cross-over intervention with two arms Fig. . The parThe intervention chocolate was Karl Fazer’s dark chocolate (70 % cacao). The participants were asked to eat seven pieces of the chocolate (7 g) daily, for a daily intake of 49 g/day. The analyzed content of proanthocyanidins  of dark chocolate was 1230 mg/100 g (fresh weight) . The darBlood samples were taken and 24 h blood pressure was measured in the beginning and end of both intervention periods. Additionally, blood pressure, weight and anthropometrics, as well as diet and physical activity, were assessed also in the beginning of the run-in period and in the end of run-out period. These visits were also for compliance checks, meetings with the study nurse, and dietary counselling.Ambulatory 24 h blood pressure  was monitored on a day of standard physical activity, with an adequate cuff for the size of the patient’s arm. Welch Allyn ABPM 6100  validated according to the protocol of the Finnish Hypertension Society, was used. The recorder was programed to take blood pressure measurements every 20 min during daytime and every 45 min during nighttime. The data were considered valid when ≥ 80 % of all measurements were acceptable. Participants kept a brief diary to record timing of activities, sleep and posture when measuring blood pressure.Cardio-Ankle Vascular Index (CAVI) was measured by VaSera . CAVI is an index reflecting the stiffness of the artery from the heart to ankles. The calculation of CAVI is based on the stiffness parameter β which is measured by carotid echography and is not affected by blood pressure . The echWeight and body composition were measured by body composition analysis device InBody720  with participants in underwear, in a fasted state, and within 20 min after bladder emptying.Blood samples were drawn after a 10–12 h overnight fast in the beginning and after the 8 wk intervention periods. Blood samples were collected for determination of lipids , glucose and insulin. Serum (without anticoagulant) and plasma (EDTA-coated tubes) were separated by centrifugation (10 min at 3000 rpm) and frozen at −20 °C until analysis. In addition, an oral glucose tolerance test (OGTT) with 75 g of glucose in 300 ml water was administered to all participants before and after the intervention periods.AUC, InsAUC) were calculated from 0 (fasting), 15, 30, 45, 60, 90 and 120 min serum glucose and insulin concentrations using the trapezoid rule [Total cholesterol, triglyceride, HDL- and LDL cholesterol concentration were measured enzymatically. Glucose was measured by the hexokinase method and insulin was assayed by the chemiluminescent immunoassay method. To assess glucose response and total insulin secretion, areas under the response curve to glucose and insulin  five times during the study . The consumption of all foods and drinks was recorded during these days. Household measures and standard units were used to describe amounts of foods consumed. The volunteers received detailed instructions on how to fill in the diaries, and a nutritionist performed an interview to review and clarify the food records. Food and nutrient intakes were calculated by using AivoDiet software , which is based on Fineli, the Finnish food composition database . According to self-report, all participants consumed the requested daily amount of dark chocolate. Additionally, the participants refrained from consuming cocoa or chocolate from sources other than the study products during the dark chocolate intervention and control periods. Moreover, the participants did not consume any milk or dark chocolate during the run-in, run-out, or wash-out periods.Participants were asked to maintain their usual level of physical activity during the study. Additionally, participants’ physical activity and health status, use of medication, as well any adverse events, were evaluated by a questionnaire concerning the previous week before the data collection.t test for independent samples. Differences in the variables measured between the chocolate and control periods were analyzed with repeated measures ANCOVA, and baseline value as covariate were used. The power calculation was based on data from the meta-analysis by Reid et al. [Statistical analyses were performed by using IBM SPSS Statistics for Windows . The normality of the analyzed variables was tested using Shapiro-Wilk’s W-test. If the distribution was not normal, logarithmic transformations were done before the analyses. The differences for the variables between two arms at the baseline were tested with Student’s d et al. . The reqThere were no significant differences in measured variables between the two arms at baseline. Neither 24 h nor clinical blood pressure was significantly affected by the dark chocolate intervention. However, blood pressure decreased significantly over the entire study. Twelve of the 22 participants’ status improved from hypertensive to normotensive. From baseline to the end of the study, mean (SD) systolic and diastolic blood pressures among all participants were reduced by 7 mmHg (12.2) and 3 mmHg (7.9), respectively . The intervention trial had no effect on CAVI.Weight decreased 1.0 kg ± SD 2.2) after the control period where no dark chocolate was consumed  of the peripheral conduit arteries is one of the most widely used tests of endothelial function. CAVI is a new method which reflects the stiffness of the whole arterial segment, and it correlates with FMD . CAVI chIn contrast to results from our study, consumption of dark chocolate has had a beneficial effect on vascular function by improving endothelial function, measured by flow mediated dilatation both in short-terms  interventions , 37 and In the one-year intervention study of Curtis et al.  conductePrevious studies on dark chocolate and glucose metabolism have shown positive or neutral effects , 40. In Dark chocolate contains saturated fatty acids which have shown to be atherogenic. However, the overall atherogenic effect of a product  is modulated by many other ingredients, not only saturated fatty acids. For instance, chocolate also contains linoleic and oleic acids, known to modulate cholesterol metabolism in a health-promoting way. Despite its saturated fatty acid content, dark chocolate has lowered both total- and LDL cholesterol in previous studies , 30, 32 In most studies, consumption of dark chocolate has not had any impact on triglycerides, with the exception of two studies where acute consumption increased triglyceride concentration  and an iProportion of body fat and total fat mass tended to decrease during the study periods, but the change was not significant. The result of the present study is similar to previous studies , 51 whicSeveral intervention studies have shown that consumption of dark chocolate may have beneficial effects on cardiovascular health , 53. EveIn this study, the reduced snack consumption and inclusion of 49 g dark chocolate daily as part of a diet of mildy hypertensive participants had no significant effects on cardiovascular risk factors during 8 wks. Perhaps the positive effects were already caused by the decreased snack intake and therefore, the addition of dark chocolate failed to produce beneficial effects. However, apart from a small effect on body weight (dark chocolate seemingly prevented a slight decrease in body weight during the control period), no other negative effects were observed.


The jugular venous pulse (JVP) provides valuable information about cardiac haemodynamics and filling pressures and is an indirect estimate of the central venous pressure (CVP). Recently it has been proven that JVP can be obtained by measuring the cross-sectional area (CSA) of the IJV on each sonogram of an ultrasound B-mode sonogram sequence. It has also been proven that during its pulsation the IJV is distended and hence that the pressure gradient drives the IJV haemodynamics. If this is true, then it will imply the following: (i) the blood velocity in the IJV is a periodic function of the time with period equal to the cardiac period and (ii) the instantaneous blood velocity is given by a time function that can be derived from a flow-dynamics theory that uses the instantaneous pressure gradient as a parameter. The aim of the present study is to confirm the hypothesis that JVP regulates the IJV blood flow and that pressure waves are transmitted from the heart toward the brain through the IJV wall.  Wave a corresponds to the atrial contraction and is synchronized with the P wave of the electrocardiogram (ECG). Descent x corresponds to the lowering of the atrioventricular septum, interrupted by a small positive wave c in relation to the closure of the tricuspid valve; the third wave v corresponds to the cardiac systole and is followed by the y descent which corresponds to the opening of the tricuspid valve.The evaluation of the jugular venous pulse (JVP), defined as the movement of expansion of the jugular vein due to changes in pressure in the right atrium, provides valuable information about cardiac haemodynamics and filling pressures , characta, c, and v waves as the JVP. Our study gave a quantification of the IJV CSA variation during the cardiac cycle. We also have seen that the IJV perimeter, measured on each sonogram of the video clip, was correlating with the IJV CSA (R > 0.9). On this point, we believe that it is desirable to have a confirmation of this finding also using a different imaging modality. However, a direct explanation of this finding is that, when in supine position, the pulsation of the IJV is a distension of its wall. This result is very important because it means that there is a time varying transmural pressure whose effect is clearly visible and cannot be neglected; in fact, large changes in transmural pressure are required to induce CSA deformation accompanied by a stretching of the wall : of the time axes while PW is the distance in pixels between the 0 and 100 cm/s divisions, measured along the y-axis. Combining the two expressions in , generates two descents in the assessed velocity time diagram within the same cardiac period. Although the relationship between the JVP and the variation of pressure in the heart has been known since 1902 [The main result of the present study is the well apparent relationship between the blood velocity in the IJV measured by the current Doppler system and the same parameter derived from its pulse. For both subjects the presence of the two positive peak waves, “nce 1902 , until nnce 1902 –19. Thisnce 1902 , 9, 20.Our data clearly demonstrates how the assumption of the Poiseuille theorem in the case of pulsatile flow may expose the flow assessment to error. We focused our study on US but of course the MRV methodology used for IJV flow assessment could also be affected by the same incorrect assumption. We know that the distal segment of the IJV is characterized by significant CSA variation over time, an effect linked with the transmission of pressure waves from the right atrium. This phenomenon, very well known as JVP, is strongly connected with important regulators of the cardiovascular function: degree of filling, heart pulsation, and capacity of emptying of the IJV.a,” “c,” and “v” clearly show a brain directed propagation of pressure waves with significance never investigated, as yet. We know that propagation is greater when the degree of filling of the venous system is higher and/or when the heart function is compromised. Acute symptoms in the latter rapidly appear in the pulmonary function but we have never investigated if this may have significance for cognitive or neurological decline already described in this particular category of patients. We speculate that cardiac, carotid, and jugular signals should be synchronized and used to assess the circulatory axis between the heart and brain, with significant changes in current clinical practice, in neuroimaging as well.Moreover, the positive waves “The results reported here can be reproduced using MRV because CSA and blood velocity can be measured at each instant of time as we did.The Womersley approach presented in  derives However, we encourage the adoption of more sophisticated models when the blood flow has to be calculated for clinical reasons .The assumption of simple linear or quadratic relationships between CSA and pressure seems to be correct in the present case. In fact, considering the well-known “tube-law” , the CSAThe oscillating nature of the IJV is potentially relevant in the understanding of the relationship between brain drainage and several neurological disorders –29. In p


Material and Methods. The studied group consisted of 65 patients aged 1.4–18.6 (mean 11.2) years with stages 1 to 5 CKD. Serum oxidized low-density lipoprotein (oxLDL), protein carbonyl group, creatinine, cystatin C, albumin, lipids, high-sensitivity C-reactive protein, intercellular adhesion molecule-1, insulin, plasma renin activity, and aldosterone levels were measured. Patients were divided into groups depending on CKD stage. Anthropometric measurements, ambulatory blood pressure (BP) measurements, and echocardiography with left ventricular mass (LVM) calculation were performed. Results. Serum oxLDL strongly correlated with creatinine , cystatin C , total cholesterol , triglycerides , low-density lipoprotein concentrations , and 24 hour BP values of systolic , diastolic , and mean arterial pressure . A significant correlation between oxLDL levels and LVM z-scores  was found. Conclusions. Hypertension and dyslipidemia correlated with lipid oxidation in children with CKD. oxLDLs seem to be valuable markers of oxidative stress in CKD patients, correlating with left ventricular hypertrophy.Cardiovascular diseases remain the most frequent cause of morbidity and mortality in patients with chronic kidney disease (CKD). The aim of the study was to assess the association between oxidative stress biomarkers and cardiovascular risk factors and left ventricular hypertrophy in children with CKD. An imbalance between the processes of formation of free radicals and their removal with a predominance of the production of reactive oxygen species (ROS) is referred to as oxidative stress. The uncontrolled increase in the concentration of free radicals is postulated to be one of the pathophysiological mechanisms of many diseases such as diabetes, atherosclerosis, vascular dementia, or neoplasms. Under physiological conditions, ROS and reactive nitrogen species (RNS) are constantly produced to defend the body against germs and are also of importance in the processes of cell signaling, tissue healing, and remodeling . ROS incIn patients with chronic kidney disease (CKD) treated conservatively and on dialysis, both the increased production of ROS and RNS and reduced antioxidant status have been shown , 3. ActiOxidative stress is considered to be one of the cardiovascular risk factors in patients with CKD. In this group of patients higher prevalence of traditional risk factors  and uremia-related ones  is found. Many studies have shown increased morbidity and mortality from cardiovascular causes in adults with CKD. In children, because hard endpoints, such as stroke or cardiovascular death, are rarely evaluated, surrogate endpoints, such as left ventricular hypertrophy (LVH), are more frequently observed .The aim of the study was to assess the association between oxidative stress biomarkers and cardiovascular risk factors and left ventricular hypertrophy in children with chronic kidney disease.Medical examinations were carried out from June 2008 to February 2011. The study was performed in accordance with the Declaration of Helsinki of 1975 for Human Research and approved by the Bioethical Committee of the Jagiellonian University (KBET/17/B/2006). The parents and patients were informed about the objective and method of performing the study and gave their informed consent.The inclusion criterion was the age of 0–21 years and diagnosed chronic kidney disease. The exclusion criteria were lack of consent of the patient or parents, congenital heart defects or other primary heart diseases, acute infections, or failure of other organs.2), group 4: dialyzed children].On admission blood samples were taken from all patients (fasting for 12 hours). Three samples were collected and centrifuged and plasma and serum were frozen at −80°C. Biochemical analyses necessary to determine kidney function were performed and urea, creatinine, cystatin C, electrolytes, albumin, aldosterone, and lipids concentrations were measured; plasma renin activity (PRA) was assessed. On the basis of serum creatinine and cystatin C, an estimated glomerular filtration rate (eGFR) with the Schwartz  formulasTo assess oxidative stress the concentration of oxidized LDL particles, as an effect of lipid oxidation, and the concentration of carbonyl groups resulting from oxidation of proteins were used. Concentrations of serum high sensitive C-reactive protein (hsCRP) ; oxLDL ; protein carbonyl groups ; and intercellular adhesion molecule-1 (ICAM-1)  were determined with enzyme-linked immunosorbent assay (ELISA). Insulin levels  were measured using the IRMA method.z-scores based on data published by Palczewska and Niedźwiecka . Differences between the groups were compared using the Kruskal-Wallis test. Spearman's rank correlation was used to relate levels of kidney function and oxidative stress markers. Statistical calculations were performed using a commercially available statistical package (Statistica PL). A value of The studied group consisted of 65 patients (41 boys and 24 girls) aged 1.4 to 18.6 (mean 11.2) years with stage 1 to stage 5 CKD, who were under constant medical control in the University Children's Hospital in Krakow. Among diseases leading to the development of CKD in the examined children, the highest prevalence was noted in congenital abnormalities of the kidney and urinary tract, 31 (47.7%), followed by glomerulonephritis, 8 (12.3%), cystic disease, 7 (10.8%), and others, 19 (29.2%).Clinical data and basic kidney function parameters depending on the stage of chronic kidney disease are presented in p = 0.019). There were no significant differences in the concentration of most evaluated parameters  associated with oxidative stress were analyzed according to CKD stage in the studied group. There was a significant difference in median oxLDL concentration between CKD stages 3 and 5  or angiotensin receptor blocker (ARB), 63.6% in stages 1 + 2, 72.2% in stage 3, 64.3% in stage 4, and 54.5% in stage 5, respectively. There were no differences between children on ACEI or ARB and without this treatment (data on request).p = 0.024).The average concentration of oxidized LDL was 86.94 U/L and of carbonyl groups 1.69 nmol/mg. Elevated concentrations of protein carbonyl groups (>4 nmol/mg) were observed in 6 of 54 patients. The median oxLDL concentration was significantly higher in girls than in boys , albumin, insulin, hsCRP and ICAM-1, and aldosterone concentrations. Correlations of investigated parameters  with kidney function markers were performed. The most pronounced correlations were found for oxLDL: its concentration significantly correlated with creatinine , cystatin , and eGFR calculated on their basis . Furthermore oxLDL strongly correlated with total cholesterol , TGL , LDL , and 24 hour blood pressure values of SBP , DBP , and MAP  and negatively with PRA . hsCRP correlated significantly with creatinine , while insulin correlated with creatinine  and cystatin C  concentrations and eGFR calculated with the Filler formula .In the studied population there was no correlation between oxLDL and age, CKD duration, weight, body mass index (BMI) in Patients were divided into 4 groups depending on the quartiles of oxLDL concentration and clinical, biochemical, and echocardiographic parameters between groups were compared. Children with high oxLDL concentrations were characterized by significantly higher blood pressure, triglycerides, and total and LDL cholesterol levels. In this group also higher left ventricular mass was found .p = 0.567). A trend toward higher median oxLDL values in children with LVH was present  versus 81.06  U/L; p = 0.084), although it did not reach statistical significance.Echocardiographic examinations revealed LVH in 34 children. There were no significant differences in median carbonyl groups concentrations between children with and without LVH  versus 1.29  nmol/mg; z-score) . In the univariate analysis, LVM in z-scores correlated significantly with eGFR , MAP (z-score) , albumin , and oxLDL concentrations  . After exclusion of MAP from the equation 3 parameters correlated independently with LVM z-score .There was a significant correlation between oxLDL concentration and LVPWT (= 0.016) . In the This is, to our knowledge, the first study comparing oxidative stress markers and left ventricular hypertrophy in children with chronic kidney disease.Despite the enormous technological progress and the introduction of new medications into the treatment of patients with impaired renal function, this group is characterized by an increased cardiovascular risk. Mortality associated with cardiovascular causes is higher in children and adults with CKD compared to the general population . AccordiCKD patients are exposed to high prevalence of traditional cardiovascular risk factors as well as nontraditional ones, such as inflammation, oxidative stress, and endothelial dysfunction. These factors are responsible for accelerated atherosclerosis and heart damage. Fruchart et al. proposed a division of atherosclerosis risk factors into the old, the old/new, and the new . The autOur data suggest that uremia per se is a significant contributor to oxidative stress. In the studied group of children with chronic kidney disease a significant correlation between the concentrations of oxidized LDL and serum creatinine and cystatin C was demonstrated. The highest median concentration of oxLDLs was found in the group of children undergoing dialysis. Furthermore, a significant influence of traditional cardiovascular risk factors, hypertension and lipid disturbances, on the severity of oxidative stress in children with CKD was shown. oxLDL concentration correlated strongly with 24 hour systolic, diastolic, and mean arterial pressure values and with total cholesterol, triglycerides, and LDL cholesterol levels. The lack of correlation between kidney function impairment and aldosterone level as well as plasma renin activity is probably connected with wide use of nephroprotection, starting at the early stage of chronic kidney disease. From the studied population 63% of children were treated with ACEI or ARB.Statins are becoming more widely used in children, especially in those with familial hypercholesterolemia . Given tOver the last decades, several research studies investigating the role of oxidative stress in chronic kidney disease in adults were undertaken . Müller The main factor influencing the increase in left ventricular mass in our study was elevated blood pressure. Several other parameters such as high oxLDL, low albumin concentrations, and low eGFR also correlated with LVM. The studied group of children with high oxLDL levels had significantly higher LVM and left ventricular posterior wall thickness. Future studies are needed to evaluate oxLDL as a biomarker of oxidative stress target organ damage in children. Holvoet et al. proposed evaluating the concentration of circulating oxidized LDLs as means of a more accurate cardiovascular risk assessment. Adults with coronary artery disease confirmed in angiography had significantly higher concentrations of oxLDLs. A significant correlation between oxLDLs and most of Framingham risk factors was also demonstrated . In hemoIn the studied population a significant correlation between hsCRP and serum creatinine concentrations was found. It should be stressed out that in children recorded hsCRP concentrations did not exceed 3 mg/L, a value that indicates an increased cardiovascular risk associated with the severity of chronic inflammation. In adults on hemodialysis significantly higher concentration of carbonyl groups in comparison to healthy subjects was observed. Danielski and coauthors suggested that increased oxidative stress associated with inflammation and phagocytic cell activation might preferentially increase aldehyde formation and oxidize thiol groups in proteins rather than promote lipid peroxidation . In adulz-score.Chronic kidney disease is frequently accompanied by decreased albumin levels, both in adults and in children , 42. SerIn the early stages of the atherosclerotic process there is an activation of adhesion molecules, which promotes adhesion of monocytes to the vascular wall and their migration to the intima. As a result of chronic inflammation adhesion molecules belonging to the immunoglobulin family: ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular adhesion molecule-1) are being expressed on endothelial cells. In the work of Ridker et al. the growing concentration of soluble ICAM-1 adhesion molecule was one of the major cardiovascular risk factors in postmenopausal women and the risk increased 2.6-fold between the lowest and highest quartiles of ICAM-1 levels . In the In children with chronic kidney disease an increase in the concentration of oxidized LDLs with the progression of the disease was found. This biomarker of oxidative stress was strongly correlated with 24 hour blood pressure values, triglycerides, and total and LDL cholesterol levels. Oxidized LDLs seem to be valuable markers of oxidative stress in CKD patients, correlating with left ventricular hypertrophy. In contrast to adults, the protein carbonyl content did not increase in advanced stages of CKD.In the supplementary materials 4 groups of primary kidney diseases leading to renal impairment in the studied group of children , glomerulonephritis, cystic disease and others) are presented.


New-onset diabetes after transplantation (NODAT) is a common comorbidity after renal transplantation. Though metformin is the first-line agent for the treatment of type 2 diabetes, in renal transplant recipients, metformin is frequently avoided due to concerns about renal dysfunction and risk for lactic acidosis. Therefore, alternative first-line agents for the treatment of NODAT in renal transplant recipients are needed. Sitagliptin, a dipeptidyl-peptidase-4 (DPP-4) inhibitor, has a low incidence of hypoglycemia, is weight neutral, and, in a small study, did not affect immunosuppressant levels. However, long-term sitagliptin use for the treatment of NODAT in kidney transplant recipients has not been studied. We retrospectively analyzed renal transplant recipients diagnosed with NODAT and treated with sitagliptin to assess safety and efficacy. Twenty-two patients were started on sitagliptin alone. After 12 months of followup, 19/22 patients remained on sitagliptin alone with a significant improvement in hemoglobin A1c. Renal function and immunosuppressant levels remained stable. Analysis of long-term followup (32.5 ± 17.8 months) revealed that 17/22 patients remained on sitagliptin (mean hemoglobin A1c < 7%) with 9/17 patients remaining on sitagliptin alone. Transplant-specific adverse events were rare. Sitagliptin appears safe and efficacious for the treatment of NODAT in kidney transplant recipients. New-onset diabetes after transplantation (NODAT) represents a common comorbidity after solid organ transplantation. NODAT after kidney transplantation is associated with inferior outcomes, including higher risk of infections, decreased graft survival, higher rates of cardiovascular disease, and increased overall mortality –5. Risk Metformin is the first-line agent of choice for the treatment of type 2 diabetes in the general population. Though some data suggests metformin is safe in the setting of chronic kidney disease, the use of metformin in kidney transplant patients is still quite controversial due to the concern about lactic acidosis and lack of data regarding metformin use in this patient population –11. TherSitagliptin, an oral dipeptidyl-peptidase-4 (DPP-4) inhibitor, was approved in the United States in 2006 for the treatment of type 2 diabetes. Sitagliptin has a low incidence of hypoglycemia and does not promote weight gain, and the dosage can be adjusted based on renal function . These pWe hypothesized that in kidney transplant recipients sitagliptin would improve NODAT control, as assessed by hemoglobin A1c (HbA1c), with a favorable safety profile including no effect on immunosuppressant levels or graft function.http://optn.transplant.hrsa.gov/). We have previously reported an incidence of NODAT of 18% in our kidney transplant population [In this single center study, we performed a retrospective analysis of kidney transplant recipients in the Multidisciplinary Transplant Clinic at the University of Nebraska Medical Center (UNMC) between October 2006 (release date of sitagliptin in the United States) and December 2012. All subjects in this study received their kidney transplant at UNMC. Between 2009 and 2013, 125 to 149 kidney transplants were performed per year at UNMC  ≥200 mg/dL or 11.1 mmol/L) and diabetes care received at the UNMC Diabetes Center to allow for accurate record of diabetes medication changes and reporting of side effects [https://www.merck.com/).The study was approved and monitored by the UNMC Institutional Review Board. A general query was performed to identify all kidney transplant recipients who had been prescribed sitagliptin during the study dates. Data for the query and subsequent data collection for the study were obtained from review of the electronic medical records—Centricity , OTTR (OTTR Chronic Care Solutions), and Epic (Epic Systems Corporation). Inclusion criteria for the study included diagnosis of NODAT by the 2003 International Consensus Guidelines criteria  was obtained at the time of transplant, at the time of sitagliptin initiation, after 12 months of sitagliptin therapy, and at the end of followup.As part of routine posttransplant and diabetes care, patients underwent fasting labs weekly to monthly at the Clinical Laboratory of The Nebraska Medical Center including serum creatinine, tacrolimus and/or sirolimus trough levels (as appropriate), and fasting glucose levels. HbA1c was performed every 3 months and fasting lipid panel every 3 to 6 months. Serum creatinine, fasting serum glucose, HDL cholesterol, and LDL cholesterol measurements were performed using standard calibration protocols and dedicated analyzers and were assayed by colorimetric means. Tacrolimus and sirolimus levels were performed via liquid chromatography/tandem mass spectrometry. HbA1c was performed on a National Glycohemoglobin Standardization Program (NGSP) certified high-pressure liquid chromatography (HPLC) analyzer. Estimated GFR (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) equation.P < 0.05 was considered significant.Data is presented as mean ± SD. Paired groups were analyzed utilizing the Wilcoxon Signed Rank test. Nonparametric repeated measures ANOVA was used to analyze parameters at multiple time points. A total of 65 patients were identified to have received sitagliptin after kidney transplant during the study dates. Of these, 37 patients met criteria for NODAT . Of thesn = 19) who remained on sitagliptin alone for the entire 12 months (data not shown). There was a modest but significant decrease in BMI from the start of sitagliptin to the 12-month followup  was no different than at start of sitagliptin Figures . We alsoTo assess the long-term efficacy and risk for adverse effects of sitagliptin in kidney transplant recipients, we followed our cohort from the initiation of sitagliptin until December 2012 or discontinuation of sitagliptin, whichever came first . In the cohort, 17/22 patients remained on sitagliptin throughout the study period, for a mean duration of sitagliptin use of 37.9 ± 16.5 months. Of these 17 patients, 9 remained on sitagliptin alone for the entirety of the study (31.8 ± 18.7 months). Diabetes was well controlled in this group, with HbA1c maintained below 7% (6.5 ± 0.5%) at the end of followup .n = 4; insulin, n = 4). HbA1c remained well controlled in this group (Eight patients continued on sitagliptin for the duration of the study (44.9 ± 10.9 months) but required addition of other diabetes medications to maintain glycemic control  compared to patients who discontinued sitagliptin and were switched to more aggressive diabetes management (n = 5)  suggesting the need for intensification of diabetes therapy in the sitagliptin discontinuation group was not necessarily related to weight gain.Hemoglobin A1c was significantly lower at baseline in patients who were able to continue on sitagliptin alone for the duration of the study ( (n = 5) . Change Glucagon-like peptide-1 (GLP-1) therapies have been implicated to potentially increase the risk of pancreatitis, a matter of significant controversy. In the current study, no episodes of pancreatitis were reported during the follow-up period. Additionally, other transplant-specific adverse events were rare in our cohort, including one episode of acute rejection (47 months after sitagliptin initiation); two episodes of opportunistic infections (13 and 14 months after sitagliptin initiation); no graft loss; and one death (due to end-stage liver disease).Our study represents the largest cohort investigating the safety and efficacy of sitagliptin for the treatment of NODAT in kidney transplant recipients. Though our study was retrospective, through meticulous review of the medical records of patients followed up primarily in our transplant endocrine clinic we were able to closely follow medication prescribing changes, laboratory values, and reports of potential side effects and transplant-related comorbid events. In our cohort, sitagliptin was efficacious with a majority of patients meeting a goal HbA1c <7%. Specifically, sitagliptin alone was adequate to improve and maintain glycemic control in a majority of patients 19/22) for 12 months after sitagliptin initiation, consistent with its efficacy in the nontransplant population , 22. for 12 mSitagliptin inhibits DPP-4 with several subsequent effects that improve blood glucose control including potentiation of insulin secretion and inhibition of glucagon secretion. In studies utilizing animal models of type 2 diabetes, sitagliptin has also been shown to reduce islet inflammation and protect beta cell mass –25. SitaIn solid organ transplant recipients, drug-drug interactions and adverse effects of medications on graft function are of paramount importance when considering medications to treat comorbid conditions. We set out to better define the safety profile of sitagliptin in kidney transplant recipients in terms of effects on immunosuppressant levels/dosing, graft function, and other side effects. Renal function and tacrolimus and sirolimus dosing and trough levels remained stable during the initial 12-month follow-up period, indicating sitagliptin does not adversely affect renal function or interfere with immunosuppressant dosing. This is consistent with and extends upon similar data published from our center . HypoglyThe use of DPP-4 inhibitors for the treatment of hyperglycemia and NODAT in kidney transplant recipients is gaining more interest. Recently, a 3-month clinical trial of vildagliptin, another oral DPP-4 inhibitor, revealed that this agent improved oral glucose tolerance test outcomes and modestly improved hemoglobin A1c in kidney transplant recipients with impaired glucose tolerance (IGT) . SimilarLimitations of our study include the retrospective nature of our study and the small cohort size. However, large, prospective studies regarding glucose-lowering therapy for NODAT do not exist currently (as reviewed) and our study represents the largest study to date examining the use of sitagliptin in the setting of NODAT after kidney transplantation . Our cohIn conclusion, we have shown that, in a small cohort of kidney transplant recipients who developed NODAT, sitagliptin was efficacious as a single agent or in combination with other glucose-lowering medications. Sitagliptin was also well tolerated and renal function and immunosuppressant levels and dosing were stable during 12 months of therapy. Sitagliptin may be valuable as a first-line agent in kidney transplant recipients diagnosed with NODAT who are candidates for oral therapy.


Blood pressure monitoring is essential in managing hemodynamically unstable neonates and preterm infants. Non-invasive blood pressure measurement (NIBP) with oscillometric technique is in widespread use in the Neonatal Intensive Care Units (NICUs). Nonetheless NIBP is not pretty accurate when compared with invasive monitoring since it generally over read mean blood pressure in particular when the infants are hypotensive so it falsely reassures neonatologists -4. InvasIn conclusion invasive arterial blood pressure technique, if correctly performed by neonatologists and closely monitored by nurses, represents a valuable tool to tailor treatment in very ill preterm neonates.


Thermogenic (TRM) supplements are often used by people seeking to decrease body weight. Many TRM supplements are formulated with multiple ingredients purported to increase energy expenditure and maximize fat loss. However, in the past some TRM ingredients have been deemed unsafe and removed from the market. Therefore, it is important to verify the safety of multi-ingredient TRM supplements with chronic consumption.To assess the safety of daily consumption of a multi-ingredient TRM supplement over a 28-day period in healthy adults.n=9) or remain unsupplemented  for 28 days. Participants maintained their habitual dietary and exercise routines for the duration of the study. Fasting blood samples, resting blood pressure, and heart rate were taken before and after the supplementation period. Samples were analyzed for complete blood counts, comprehensive metabolic, and lipid panels.Twenty-three recreationally active adults  were randomly assigned either to consume a multi-ingredient TRM supplement  group by time interactions were present for diastolic BP, creatinine, estimated glomerular filtration rate (eGFR), chloride, CO2, globulin, albumin:globulin (A/G), and high-density lipoprotein (HDL). Dependent t-tests conducted on significant variables revealed significant (p<0.05) within-group differences in SUP for diastolic BP (+6.2±5.3 mmHG), creatinine (+0.09±0.05 mg/dL), eGFR (−11.2±5.8 mL/min/1.73), globulin (−0.29±0.24 g/dL), A/G (+0.27±0.23), and HDL (−5.0±5.5 mg/dL), and in CRL for CO2 (−1.9±1.5 mmol/L) between time points. Each variable remained within the accepted physiological range.Significant (p<0.05) intragroup differences in SUP from pre- to postsupplementation for diastolic BP, creatinine, eGFR, globulin, A/G, and HDL, all remained within accepted physiological ranges and were not clinically significant. In sum, it appears as though daily supplementation with a multi-ingredient TRM is safe for consumption by healthy adults for a 28-day period.Results of the present study support the clinical safety of a multi-ingredient TRM containing caffeine, green tea extract, and cayenne powder. Although there were statistically significant ( Over the past decade, the prevalence of overweight and obesity in the United States has continued to rise, with approximately two-thirds of the adult population fitting into these categories . As the Many TRM supplements are formulated with multiple ingredients purported to increase energy expenditure (EE), increase fat oxidation, or suppress appetite. Stimulants such as caffeine anhydrous and green tea extract are often combined to achieve these effects. Caffeine is a sympathetic nervous system stimulant known to increase EE and fat oxidation following acute ingestion , 6. GreeHowever, caution must also be exercised when considering TRM supplements that combine multiple active ingredients. As has been the case in the past, some of the most efficacious TRM ingredients have been deemed unsafe for consumption and subsequently removed from the market by the Food and Drug Administration. Ephedra and 1,3-dimethylamylamine (DMAA) provide two such examples , 12, wheIt is therefore prudent to verify the safety and potential side effects of TRM supplements currently on the market. The purpose of the present study was to assess the clinical safety of daily consumption of a multi-ingredient TRM supplement containing caffeine, green tea extract, and capsaicin-containing cayenne fruit powder over a period of 28 days in healthy men and women. It was hypothesized that daily supplementation would not produce abnormal changes in hematological or metabolic safety markers or resting vital signs.n=14; 26.5±5.9 years, 173.6±9.1 cm, 77.0±17.8 kg) or supplement  groups via random number generation by the investigators and asked either to remain unsupplemented or consume two servings, respectively, of a commercially available TRM  every day for 28 days. Supplement facts are listed in In a randomized design, 23 subjects  were randomly assigned to control  participated in the present study. Recreationally active was defined as habitually participating in moderate to vigorous physical activity on three or more days a week for a duration of 30 min or more. Subjects were required to be non-smokers, free of any disease or disorder which may have produced confounding effects, and have abstained from taking any other TRM or weight-loss supplements for 1 month prior to the beginning of the study. Eligibility was determined upon evaluation of preparticipation health history, exercise, and supplementation screening questionnaires. Subjects were instructed to maintain their habitual dietary and exercise routines and not to take any additional supplements during their participation in the study. Furthermore, participants were cautioned against changing any aspect of their current diet and exercise regimen in attempts to decrease body weight.Twenty-three recreationally active adults , calcium, protein, albumin, globulin, albumin:globulin (A/G) ratio, bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and low density lipoprotein (LDL) cholesterol. Intertest reliability results from 12 men and women measured up to 1 week apart at the aforementioned laboratory resulted in no significant differences from day-to-day (p>0.05) and an average intertest Coefficient of Variation of <6.9% for all tests.All measurements were taken prior to and following the 28-day supplementation period. Upon arrival at the laboratory, height and weight as well as resting blood pressure and heart rate were recorded using a high-capacity column scale with built-in stadiometer , and an automated digital sphygmomanometer , respectively. Subjects then submitted a blood sample in the morning following an overnight fast to control for diurnal fluctuations. Blood draws were performed by a trained phlebotomist via venipuncture, and samples were analyzed for comprehensive metabolic panels, complete blood counts, and lipid profiles by an external laboratory . Variables recorded from blood analysis consisted of white blood cell count (WBC), red blood cell count (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), platelets (absolute), neutrophils (percent and absolute), lymphocytes (percent and absolute), monocytes (percent and absolute), eosinophils (percent and absolute), basophils (percent and absolute), serum glucose, blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR), BUN:creatinine, sodium, potassium, chloride, carbon dioxide (COp<0.05 level of significance. Variables demonstrating a significant (p<0.05) group by time interaction were then analyzed for within-group differences using dependent t-tests, in addition to independent t-tests conducted on the mean delta values to examine between-group differences in change over time. Shapiro–Wilk tests were used to determine normality of the data. The minimal difference (MD) needed to be considered real was determined using the method previously described by Weir  group by time interactions were observed for diastolic blood pressure, creatinine, eGFR, chloride, CO2, globulin, A/G ratio, and HDL cholesterol. Dependent t-tests revealed within-group differences between time points in SUP for diastolic blood pressure , creatinine , eGFR , globulin , A/G ratio , and HDL cholesterol . In CRL, dependent t-tests revealed intragroup differences for CO2 from pre- to postsupplementation . For chloride, neither group reached significance (p>0.05) for dependent t-tests. Each of the aforementioned variables remained within accepted physiological reference ranges and were normally distributed (p>0.05) at both time points. Body weight was not significantly different either within or between groups from pre- to posttesting . No other variables had significant group by time interactions. Data are presented as means±SD in Significant (p<0.05) were observed for diastolic blood pressure, creatinine, eGFR, chloride, CO2, globulin,A/G ratio, and HDL cholesterol, each of these variables remained well within the accepted physiological range and are not clinically significant. In addition, dependent t-tests did not reach significance (p>0.05) for intragroup differences in SUP for chloride or CO2.The results of the present study support the hypothesis that daily TRM supplementation does not appear to cause abnormal changes in hematological and clinical chemistry or metabolic safety markers or resting vital signs in healthy adult subjects. While significant group by time interactions  needed to be exceeded in order for a single measurement to be considered real, as described by Weir . If a sun=6) and short duration of the study.The present findings agree with previous literature. Roberts et al.  examined−2) individuals, not moderately overweight and/or obese individuals, which may be more representative of the population to which this product is likely to appeal. Perhaps another limitation is the age of the participants (27.1±5.4 years), which may make the present findings less applicable for older populations. Similar studies involving either moderately overweight or obese and older subjects are therefore warranted. Follow-up investigations may also examine the supplement's effect on EE, substrate utilization, and efficacy as a weight loss aid.The present study adds to the existing literature, suggesting that a multi-ingredient TRM containing caffeine, green tea extract, and cayenne powder is safe for daily consumption up to 28 days, at least with regard to hematological and metabolic clinical markers of safety and hemodynamics. Again, while none of the significant variables left the accepted physiological range, the possibility that they might indicate the beginning of adverse trends cannot be ruled out. Future studies should examine the effects of supplementation for longer than 28 days among more subjects, especially given the fact that statistically significant interactions did take place over time in the present study. In addition, the present study involved only modestly overweight (average BMI of 26±5 kg·mDaily supplementation with a multi-ingredient TRM does not appear to have adverse effects on markers of clinical safety or resting vital signs among healthy, recreationally active adults for a period of 28 days. The results suggest that chronic consumption of the multi-ingredient TRM supplement used in the present study is safe in healthy, young individuals for up to 1 month. Future investigations may seek to expand on the current findings by utilizing a longer supplementation period and a larger sample size to verify long-term safety.Click here for additional data file.


Patients with cervical spondylosis myelopathy (CSM) and complicated with hypertension are often experiencing a blood pressure decrease after taking cervical decompressive surgery in clinical observations, but how this blood pressure reduction is associated with the surgery, which cut cervical sympathetic nervous, has never been rigorously assessed. Thus, the purpose of this study is to investigate the effect of cervical decompressive surgery on blood pressure among CSM patients with hypertension.The study will be a time series cohort study. Fifty eligible patients will be selected consecutively from the Peking University First Hospital. Two 24-h ambulatory blood pressure measurement (ABPM) will be taken before the surgery, apart by at least 3 days. The patients will be followed up for another two ABPMs at 1 and 3 months after the surgery.We will recruit subjects with cervical spondylosis myelopathy meeting operation indications and scheduled for receiving cervical decompressive surgery, aged 18–84 years, have a history of hypertension or office systolic blood pressure ≥140 mmHg on initial screening, and willing to participate in the study and provide informed consent. Exclusion criteria includes a history of known secondary hypertension, visual analogue scale (VAS) score ≥4, and unable to comply with study due to severe psychosis.nd and 3rd , 4th measurements (before and after the surgery). We will also calculate the regression-to-the-mean adjusted changes in systolic ABP as sensitivity analysis. Secondary endpoints are the changes in 24 h ABPM diastolic blood pressure, blood pressure control status, the use and dose adjustment of antihypertensive medication, and the incidence of operative complications. Primary outcome analyses will be carried out using analysis of covariance, as well as the first secondary endpoint.The change in systolic ABPs over the four times will be analyzed to observe the overall pattern of the blood pressure change in relation to the surgery, but the primary analysis will be the comparison of systolic ABP between the 2This study will inform us the important knowledge about cervical sympathetic nervous system (SNS) and blood pressure. Once confirmed, it may help to produce new method for control of hypertension, which is the leading cause of death in the world.NCT02016768).The study is registered to Clinical Trials.gov ( Hypertension is a major global health concern. It is estimated that 30–40 % of the adult population in the developed world are suffering from hypertension , 2. MoreIt is well known that sympathetic nerve fibers are rich in cervical spinal tissues –11. YamaTamura  found thNCT02016768. Figure The study is a time series cohort study. Patients with both cervical spondylosis myelopathy and hypertension are invited to participate in the study and subsequently receive cervical decompressive surgery. Patients are recruited continuously by surgeons at the Department of Orthopaedics, Peking University First Hospital in which there are about 30–40 patients with both cervical spondylosis myelopathy and hypertension each year. These subjects will be followed up at 1 and 3 months post-operation after enrollment. The study procedures and informed consent form have been approved by the Institutional Review Boards of the Peking University Health Science Center in Beijing, China, and registered at Patients with cervical spondylosis myelopathy, such as bilateral hand clumsiness and numbness, walking unsteady, weakness in the limbs, muscular dystrophy, increasing deep tendon reflex and positive Hoffmann and Babinski signs; the underlying diseases including multilevel cervical spinal stenosis, ossification of posterior longitudinal ligaments (OPLL), disc herniation, meeting operation indications: spinal neurological symptoms for at least 2 months, which are not cured by conservative treatment or in progression, significant spinal compression indicated by magnetic resonance imaging.Aged 18–84 years.Plans for receiving cervical decompressive surgery.A history of hypertension or office systolic blood pressure ≥140 mmHg on initial screening.Willing to participate in the study and sign informed consent.The patients to be included in the study should meet the following inclusion criteria:A history of known secondary hypertension.Visual analogue scale (VAS) score ≥4.Unable to comply with study due to sever psychosis.If one of the following criteria is met, patients will be excluded from the study:The patients who suffer from cervical spondylosis myelopathy and plan for receiving cervical decompressive surgery will be selected for potential participation by the surgeons at the Department of Orthopedics. After consultation with inpatients and outpatients and screening their clinical information, the principal investigator of the study (the surgeon) informs patients whether they are eligible for the study. Informed consent is acquired immediately after screening for every subject by the principal investigator.Subjects can withdraw from the study at any time for any reason without any consequences. The investigator can also decide to release a subject from the study for medical reasons. For every subject who decides to withdraw from the study, the reasons for withdrawal will be recorded.A total of 18 patients have given informed consent for participation and been enrolled into the study from July 2014 to Oct 2015.The cervical decompressive surgery will be done with one of the following four operating methods: international standard anterior cervical discectomy and fusion , anterior cervical corpectomy and fusion , posterior bilateral open-door decompression (modified Hemo anchored method) or one-side open door decompression (modified Hirobayashi anchored method). The indications for anterior approach are subjects with less than three levels disc herniation, while for posterior approach are those with multilevel cervical spinal stenosis and continuous or mixed OPLL.After providing informed consent, potential participants will be asked standardized questions about their demographic characteristics and medical history  at initial screening. In addition, office blood pressure, VAS score and 24 h ambulatory blood pressure measurement (ABPM) will also be measured and used for checking inclusion/exclusion criteria  and the systolic ABPM at 1 month and 3 month post-operation (3rd and 4th measurement).The primary endpoint is estimated as the difference between systolic ABPM before surgery (2Four secondary endpoints were defined as: 1) The difference between diastolic ABPM before surgery and ABPM diastolic blood pressure at 1 month and 3 month post-operation; 2) control status of blood pressure at 1 month and 3 month post-operation ; 3) the use and dose adjustment of antihypertensive medication; and 4) the incidence of operative complications, including spinal nerve trauma, incision infection and fluid, pneumonia and urinary system infection etc.Based on previous study which explored the efficacy of renal sympathetic denervation in treating hypertension, we assume that for the current study the primary outcome (the change of 24 h ABPM systolic blood pressure from pre-operation to the measurement at 3 months post-operation) has a standard deviation of 15 mm Hg . We wishnd and 3rd, 4th measurements (before and after the surgery). We will also calculate the regression-to-the-mean adjusted changes in systolic ABPMs as sensitivity analysis. Primary endpoint analyses and the change in systolic ABPMs over the four times will be carried out using analysis of covariance, as well as the first secondary endpoint (the change of 24 h ABPM diastolic blood pressure). Descriptive statistics will be used to summarize control status of blood pressure, the use and dose adjustment of antihypertensive medication and the incidence of operative complications.Analyses will be made using SAS statistical software (version 9.3) by researchers at the Peking University Clinical Research Institute. The change in systolic ABPMs over the four times will be analyzed to observe the overall pattern of the blood pressure change in relation to the surgery, but the primary analysis will be the comparison of systolic ABPM between the 2The etiology and mechanism of essential hypertension remains unclear. Non-operative methods of essential hypertension treatment including antihypertensive pharmacologic drugs are still unsatisfactory , 8. In tThrough long–term clinical observations, we have found that high blood pressure or fluctuated blood pressure among many patients decreased substantially or became stable post-operatively. Therefore, we infer that cervical decompressive surgery may be a novel alternative in treating hypertension and will effectively reduce blood pressure in patients with cervicogenic hypertension. Therefore, a substantial number of patients with both hypertension and cervical spondylosis may benefit from this approach as the decrease in the quantity and/or dose of antihypertensive drugs would subsequently lead to fewer side effects from them. Regarding the rationale for the reduction on blood pressure, we speculate that the compression or irritation of the dura mater and the posterior longitudinal ligament of the cervical spine may increase the sympathetic nervous activation. This discharge may pass through the ganglia and the sympathetic trunk to the postganglia fibers arriving at the target organ, such as the vertebral artery and the blood vessels and subsequently induce hypertension. Decompressive cervical surgery, either anterior cervical discectomy and fusion or posterior laminoplasty, may withdraw any compression of the dura and the posterior longitudinal ligament and thus the sympathetic irritation will be relieved leading to a decrease of blood pressure.Our study has a number of limitations. This is not a randomized controlled clinical trial, factors such as placebo and Hawthorne effects cannot be ruled out entirely. However, we tried to measure blood pressure two times both before and after the surgery, these multiple measurements would help to better understand if the change in blood pressure is attributed to the surgery or purely to the regression to the mean. Although the randomized controlled trial is the gold standard study design, it is unethical to conduct such a trial considering the inappropriateness of treating hypertension with a cervical decompressive surgery. In our opinion, the study still gains important scientific information. Once our hypothesis is approved, it will provide an innovative mechanism of hypertension development, which may lead to the development of new methods of hypertension treatment and prevention.


Background. There are several studies investigating the relationship between androgenetic alopecia (AGA) and metabolic syndrome (MS) with conflicting results. Objective. We sought to investigate whether there is a relationship between AGA and MS. Methods. A case-control study including 74 male patients with AGA and 42 male controls was conducted. Age, duration of AGA, AGA onset age, anthropometric measures, body mass index, lipid parameters, fasting blood glucose, blood pressure, and presence of MS were recorded. Results. Of the 74 male AGA patients , 24 were in stage 2, 26 were in stage 3, 17 were in stage 3V, 1 was in stage 5, and 6 were in stage 7. There was no significant difference in the rate of MS between AGA and control groups (P = 0.135). Among the evaluated parameters, only systolic blood pressure in AGA group was significantly higher than control group. Conclusion. In contrast to the most of the previous studies, our study does not support the link between AGA and MS. To exclude confounding factors such as advanced age and therefore metabolic disturbances, further studies are needed with large group of AGA patients including different age groups and varying severity. Androgenetic alopecia (AGA) is a hair loss in specific patterns depending on circulating androgens in genetically predisposed men and women. Androgenetic alopecia affects 80% of men by the age of 70 years. In women, the incidence of AGA is 2–5% by the age of 50 and the ratio rises to 40% at age of 70. Although the main etiological factors are the same, phenotypic manifestations are different in men and women. Men usually have bitemporal and vertex hair loss leading to the complete baldness. In women, frontal hairline is usually preserved and complete baldness does not occur .Metabolic syndrome (MS) is a group of metabolic disorders such as glucose intolerance, insulin resistance (IR), central obesity, dyslipidemia, and hypertension associated with increased risk of cardiovascular disease . There aBeing between 20 and 50 years of age.Absence of a known glucose metabolism disease.Absence of a known coronary artery disease.No history of drug use that affects carbohydrates metabolism .Between August 2012 and January 2013, a case-control study including 74 patients with AGA and 42 male controls was conducted in the Dermatology Outpatient Clinic of Haseki Training and Research Hospital, Istanbul. Ethic committee approval was obtained prior to the study. Inclusion criteria for patients with AGA were as follows:The control group included age- and gender-matched male patients who have the inclusion criteria and admitted to the outpatient clinic with various dermatological complaints except alopecia.AGA group included the patients who admitted to our outpatient clinic for alopecia or any dermatological problems that meet the inclusion criteria. Diagnosis of AGA was based on characteristic clinical findings. For grading AGA; Hamilton-Norwood classification was used in the patient group , 9.2). Lipid parameters and FBG levels were studied after a 12-hour fasting period. Triglyceride level >150 mg/dL and HDL level <40 mg/dL were recommended as cutoff for dyslipidemia. FBG level ≥100 mg/dL was recommended as cutoff for impaired fasting glycemia. Systolic BP ≥135 mmHg and diastolic BP ≥85 mmHg were recommended as cutoff points for hypertension. The onset age, the duration of AGA, smoking history, and sports life were also recorded. The onset age of ≤35 years was recommended as early-onset AGA.Age, anthropometric measures , body mass index (BMI), lipid parameters , fasting blood glucose (FBG), blood pressure values of the participants' were evaluated. Waist circumference (WC) levels of >94 cm were recommended as cutoff point for abdominal obesity. BMI was calculated using the formula weight (kg)/height , waist circumference >94 cm and at least two of the following criteria, triglyceride value >150 mg/dL or specific treatment for this lipid abnormality, high density lipoprotein <40 mg/dL or specific treatment for this lipid abnormality, blood pressure ≥130/85 mmHg or antihypertensive treatment, and fasting blood glucose ≥100 mg/dL or diagnosed diabetes mellitus, were accepted as MS [In all patients, complete blood count, serum iron, total iron binding capacity, serum ferritin, free T3, free T4, and thyroid stimulating hormone (TSH) were performed to determine possible iron deficiency anemia and thyroid disorders.t-test and Mann-Whitney u test were used for the analysis of quantitative data. The chi-square test was used for the analysis of categorical data. P < 0.05 was assessed as significant.For the data analysis, the statistical program “SPSS for windows 21.0” was employed. Mean, standard deviation, ratio, and frequency were used for descriptive statistics of the data. The distribution of variables was checked with Kolmogorov-Smirnov test. Independent samples Seventy four male AGA patients  and 42 controls  were investigated. Of 74 AGA patients 24 (32.4%) were in stage 2, 26 (35.1%) were in stage 3, 17 (23%) were in stage 3V, 1 (1.4%) was in stage 5, and 6 (8.1%) were in stage 7 according to Hamilton-Norwood classification.P > 0.05). AGA group had significantly high systolic blood pressure levels and control group had significantly high FBG and waist circumference levels (P < 0.05) (P > 0.135).In AGA group, there were no significant differences in the participants' age, weight, height, BMI, sport life, TG, total cholesterol, HDL, LDL, and diastolic pressure values ( < 0.05) . There w < 0.05)  (P > 0.1P > 0.05).In AGA group, the onset age of AGA and the duration of AGA were not significantly different in the patients with or without MS (P < 0.05).When patients with stages I–IV were assessed as mild-moderate and patients with stages V–VII were assessed as severe, there was no significant difference between the patients with or without MS  and fatal ischemic heart disease has been shown, but explaining mechanisms are not clear . AndrogeEven though some studies undetected a relationship between AGA and MS, it has been found in many and has emphasized the importance of early diagnosis. In contrast to previous reports, we did not find a relationship between AGA and MS. Although there was no correlation between AGA and MS, to detect an increase in systolic blood pressure levels may be remarkable in terms of being a cardiovascular disease risk factor. Moreover, this low rate of MS may be related to the fact that our study did not include elderly patients and majority of our patients had mild alopecia compared to the other studies. On this topic, there is a need of large group of AGA patients including different age groups and varying severity.


Better understanding is needed for antihypertensive medication initiation and lifestyle modification among younger populations with elevated blood pressure. This study aimed to assess health behavior change after receiving a report of elevated blood pressure among African Americans and Caucasians younger than 50 years old. We used the Coronary Artery Risk Development in Young Adults (CARDIA) repository dataset. By examination year twenty, 424 out of 2,478 Caucasian and 2,637 African American participants had received feedback from the CARDIA study due to elevated blood pressure readings. Blood pressure was measured by trained CARDIA researchers at the participant’s home and was repeatedly recorded at seven examinations over twenty years. A feedback/referral letter was sent to participants with an elevated blood pressure reading. On average, participants first had an elevated blood pressure reading at the age of 34. After receiving the feedback letter, 44% of the previously undiagnosed participants received a formal diagnosis. In addition, 23% initiated the use of antihypertensive medication if they had not received medication treatment before. Among the participants with at-risk lifestyle behaviors, 40% reduced alcohol consumption, 14% increased exercise level, 11% stopped smoking, and 8% reached normal weight. While none of the studied patient factors were associated with lifestyle modification, age had a positive impact on antihypertensive medication initiation (p<0.05). We found no evidence of differences in health behavior change between African American and Caucasian participants after receiving the feedback letter. This research is one of the first to study what followed after receiving a feedback letter about elevated blood pressure outside of healthcare settings. Although additional referral care and behavior interventions are needed to facilitate medication initiation and lifestyle modification, our observations suggest that providing blood pressure feedback may have promise as part of a multi-method approach involving blood pressure screening and follow up. According to the Centers for Disease Control and Prevention, nearly one third 30%) of American adults live with hypertension.,2 Despit0% of AmeOne important approach to achieve these goals is to initiate guideline-recommended medical treatment in the early stage and address modifiable risk factors early in life to delay or prevent hypertension related complications and comorbidities such as CVD events and chronic renal insufficiency. The current guidelines released by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure JNC 8) provide specific recommendations to initiate antihypertensive medication and modify lifestyle behaviors in an effort to manage hypertension. However, provide Simple screening services such as blood pressure testing and feedback have the potential to motivate lifestyle modification and improve condition awareness and treatment. Thus, this study sought to assess health behavior change after elevated blood pressure was reported to African American and Caucasian individuals younger than 50 years old, with a focus on antihypertensive medication initiation and lifestyle modification. Andersen’s model of health care utilization behavior was adopted in this study to identify factors that could potentially facilitate or impede the health behavior change. The modeAs shown by The study was approved by University of Wisconsin-Madison’s Institutional Review Board. Informed consent was not obtained since all the data were analyzed anonymously.This study used the Coronary Artery Risk Development in Young Adults (CARDIA) repository dataset. The CARDIA study was designed to investigate the natural history of cardiovascular risk in young adults. A total of 5,115 African American and Caucasian Participants were followed up seven times in 1987–1988 (Year 2), 1990–1991 (Year 5), 1992–1993 (Year 7), 1995–1996 Year 10), 2000–2001 (Year 15), and 2005–2006 (Year 20) which was the latest publicly available wave. Participants ranged from 18 to 30 years old at baseline and were between 38 and 50 years old at year 20; 72% of the total surviving sample remained in the study at year 20.[, 2000–20As shown in The CARDIA study measured blood pressure at the participant’s home at each examination point. A unique element of the CARDIA study is that a feedback/referral letter was sent to participants with elevated blood pressure readings (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg), notifying them of this aspect of their health status. The referral letter contained the value of the elevated blood pressure and advised actions, including having a repeat blood pressure evaluation. For those who reported they already had a diagnosis of hypertension, this feedback served as notification of lack of control of their blood pressure. For participants who were not diagnosed before, notification/feedback made them aware of a potential blood pressure problem and alerted them to the need to follow-up with a professional diagnosis and medical care.The dependent variables were two main types of health behavior changes: antihypertensive medication initiation and lifestyle modification.Antihypertensive medication initiation was evaluated by reported antihypertensive medication use at the subsequent examination point after receiving the blood pressure feedback, among those who did not use antihypertensive medication at the initial examination point. A participant was defined as having lifestyle modification (or not) if he/she met one or more of the following criteria:Drinking: had at-risk alcohol consumption at the initial examination point based on the National Institute on Alcohol Abuse and Alcoholism drinking categories, but decreased to moderate alcohol consumption or alcohol cessation at the subsequent examination point after the feedback.Weight control: was obese or overweight at the initial examination point, but reduced to overweight or normal weight or had more than 5% of weight loss at the subsequent examination point after the feedback; body mass index was measured and calculated by trained CARDIA investigators.Smoking: was smoking at the initial examination point, but quit smoking in the subsequent examination point after the feedback.Exercise: had low-level exercise at the initial examination point, but increased exercise at the subsequent examination point after the feedback. Exercise level was assessed and calculated using the CARDIA Physical Activity History Questionnaire. DetailedAs shown in We hypothesized that blood pressure feedback could have a different impact on patients who were unaware of their elevated blood pressure previously compared to those who did formerly know they had high blood pressure. Therefore, we classified participants into two groups based on their previous awareness of their blood pressure problem when receiving the feedback on their elevated blood pressure: Group 1 (aware) consisted of participants who reported being diagnosed with hypertension and being informed previously by a health professional, but still had an elevated blood pressure reading in the CARDIA study. Group 2 (not aware) consisted of participants who did not have a hypertension diagnosis and were not aware of elevated blood pressure before, but had an elevated blood pressure reading in the CARDIA blood pressure test.Descriptive analysis and bivariate analyses were used to describe the sample characteristics in the two groups and to understand medication initiation and lifestyle modification in the subsequent years. Multiple logistic regression models were used to explore the associations between the participants’ characteristics, captured by predisposing and enabling factors, and their behavior changes. Statistical significance was set at p<0.05 and 95% confidence intervals were calculated. Statistical analyses were performed using Stata 13 and SAS 9.3.One important limitation of this study is that elevated blood pressure reading is based on one blood pressure test. According to the National Clinical Guideline Centre, hypertension diagnosis requires repeated examination. Thus, soDuring the 20-year follow-up, 424 participants received feedback from the CARDIA study about elevated blood pressure readings. Among them, 25% were identified at examination year 1, 9% at examination year 2, 10% at examination year 5, 9% at examination year 7, 16% at examination year 10, and 31% at examination year 15.Participants’ characteristics at the initial examination point when an elevated blood pressure was first recorded are summarized in Among the participants selected for study, 110 reported being diagnosed with hypertension before but still had elevated readings in the CARDIA blood pressure test/Group 1 (aware), and 314 participants were not aware of their potential blood pressure problem before the elevated readings in the CARDIA blood pressure test/Group 2 (not aware).Comparison between the two groups revealed a significant difference in participants’ gender and educational attainment. Participants in the previously undiagnosed Group 2 were more likely to be male  and less likely to have a college degree . More than two-thirds (approximately 70%) of both groups reported having no financial hardship. There was no significant difference of race or financial hardship between the two groups.In terms of participants’ health behaviors, 31% of the participants in Group 1 were using antihypertensive medication in the initial examination. As expected, due to unawareness of their elevated blood pressure, none of the participants in Group 2 were taking antihypertensive medication. A total of 16% of the studied participants reported at-risk alcohol consumption, 71% were overweight or obese, 26% were current smokers, and 40% reported low-level exercise in the initial examination.Based on the multiple logistic regression results , the likMultiple logistic regression models were used to explore participants’ characteristics associated with the lifestyle modification . A totalSensitivity analysis was conducted among patients with diagnosed blood pressure , includiThis research is one of the first to study what followed after receiving a feedback letter about elevated blood pressure from the CARDIA study. Further it does so with a sample carefully constructed to allow comparisons of Caucasian and African American populations of a fairly comparable socioeconomic status. Most of the previous studies on hypertension awareness and blood pressure management were conducted at health care settings or were based on cross-sectional surveys such as NHANES, which did not follow behavior change in response to blood pressure evaluation. This study allowed for a careful longitudinal evaluation of health behavior change as an effort to control elevated blood pressure using a comparable biracial cohort.We found receiving feedback about elevated blood pressure was associated with an increase in the use of antihypertensive medication and receiving a formal diagnosis of hypertension for both African Americans and Caucasian participants. There was also a modest reduction in the lifestyle risk factors in the subsequent examination. Among the predisposing and enabling factors, age was the only variable significantly associated with the initiation of antihypertensive medication at the subsequent examination point. This is consistent with results in previous studies using data from a large health care system.,15 YoungOur study found a significant difference in gender and educational attainment between those who were aware of their hypertension (Group 1) and those who were not aware of their hypertension when elevated blood pressure was reported (Group 2). Those in the unaware group were more likely to be male and had lower educational attainment, which is consistent with previous studies. Using the NHANES III data, Hyman et al reported that males tended to have lower awareness of their hypertension and untreated hypertension. Our studBesides gender differences, previous study also found a racial disparity in hypertension awareness and blood pressure control. To our kcues to action or strategies to activate readiness could trigger action. In this case, a simple referral letter may have provided a “cue to action” by increasing participants’ awareness of their medical condition and motivating them to seek medical care.[This study assessed behavior change by the subsequent study examination point, which was 2–5 years after receiving the report on elevated blood pressure. We found an increase in the use of antihypertensive medication in both African American and Caucasian participants. This suggests the feedback letter may promote health care seeking behaviors. According to the Health Belief Model, cal care. This finThe largest change in at-risk behaviors in this study was that 40% of the at-risk drinkers reduced their alcohol consumption after the baseline examination letter identifying their elevated blood pressure. The alcohol consumption finding is particularly interesting in that it was not tested in earlier studies .,19 ThereThe finding of limited change in smoking, weight control and exercise is consistent with previous studies. A prior study of CARDIA participants found no change in smoking, weight control or physical activity among both African American and Caucasian participants after the occurrence of a heart attack or stroke in an immediate family member. A study Among the studied patients’ characteristics, age was significantly associated with the initiation of antihypertensive medication, while none of other factors was associated with lifestyle modification. Although the cause for this association is unknown, we found males were significantly more likely to have elevated blood pressure at a younger age (<35 years). It is possible that younger males are less likely to have doctor visits and/or to have more difficulty adopting antihypertensive medication. Further studies should be conducted in this age and gender group to better understand their needs and barriers in hypertension diagnosis and management. Gender and age differences in the onset of hypertension also need to be further examined. In addition, among participants with diagnosed hypertension, we found that African Americans were more likely to start antihypertensive medication. This is consistent with findings from the Multi-Ethnic Study of Atherosclerosis (MESA), which may be a reflection of health care provider’s awareness of higher burden of hypertension among African Americans resulting in prescription writing and decisions by African American patients to follow through with prescription acquisition, dosing, and adherence.Several study limitations should be noted. This is an observational study. So no causal relationship can be established. This study had a relatively small sample size, which limits the study design, the analysis methods and the power to detect significant differences. Several measures, including diagnosis of hypertension, were self-reported and are subject to self-report bias. However, previous work on reasons for hospitalization indicated good concordance between self-reported hospitalization history and the medical records among CARDIA participants. In additThis study suggests that a simple blood pressure feedback letter has the potential to improve condition awareness and blood pressure management in a younger population, in particular the initiation of antihypertensive medications. This appears equally true across racial and gender groups. Building on this finding, future programs could explore feedback in many forms such as providing people with their blood pressure readings at a clinic visit, in a medical electronic message or letter, at a pharmacy, or through other means.


Cardiovascular disease (CVD) is an important comorbidity of chronic kidney disease, and reducing cardiovascular events in this population is an important goal for the clinicians who care for chronic kidney disease patients. The high risk for CVD in transplant recipients is in part explained by the high prevalence of conventional CVD risk factors  in this patient population. Current transplant success allows recipients with previous contraindications to transplant to have access to this procedure with more frequency and safety. Herein we provide a series of eight patients with dilated cardiomyopathy with poor ejection fraction posted for live donor renal transplantation which was successfully performed under regional anesthesia with sedation. Renal transplantation is the treatment of choice [End stage renal disease (ESRD)  is the lf choice . Most ESf choice . Reducedf choice . The patWe describe successful conduction of renal transplant surgery in eight ESRD patients with DCM using combined spinal epidural technique (CSE).Proper preoperative assessment of all eight haemodialysis dependent ESRD patients was done. Relevant details are provided in The patients were informed of their high risk status for anaesthesia. The coagulation profile of all the patients as assessed by bleeding time, prothrombin, and partial thromboplastin time was within normal limits. Informed consent was taken for regional anaesthesia. Immunosuppressants were started two days before. All other medications were continued. Diabetics on hypoglycemics were converted on insulin. Alprazolam 0.25 mg and ranitidine 150 mg were given orally night before operation.On the day of operation, intra-aortic balloon pump device was kept ready. A five-lead ECG and pulse oximetry were connected to the patient. Oxygenation by face mask was started. Under local anaesthesia, radial artery opposite to site of arteriovenous fistula was cannulated and invasive arterial monitoring started. Right internal jugular vein was also cannulated with a 8.5 F sheath under local anaesthesia. A continuous cardiac output monitoring Swan Ganz Catheter (CCO pulmonary artery (PA) catheter, Edwards Lifesciences) was introduced through the sheath till it got wedged in pulmonary artery. In sitting position and under local anaesthesia an 18 G epidural catheter was placed in T12-L1 interspace. A test dose of 3 mL of 2% xylocaine with adrenaline was given to confirm position of the catheter. A 25 G Quincke's needle was used for injecting 12.5 mg 0.5% hyperbaric bupivacaine and 25 ug fentanyl in L2-L3 intrathecal space. Infusion of 0.25% bupivacaine with 2 ug/mL fentanyl was started via epidural catheter at 3–5 mL/hour. A loading dose of Dexmedetomidine 1 ug/kg was infused over 20 minutes and then titrated at 0.2–0.5 mg/kg/hr to reach a Ramsay sedation score  four. 50The mean ± S.D duration of surgery was 3.25 ± 0.45 hours. 2.88 ± 0.353 liters of normal saline was infused intraoperatively. Mean blood loss was 0.483 ± 0.185 liters. Packed red blood cells were used in four patients. Immediate diuresis was observed after reperfusion in all cases. Mean first hour urine output was 0.958 ± 0.160 liters.5. Noradrenaline infusion was started at 2 ug/min and titrated to maintain SVR and mean arterial pressure. Dobutamine infusion was started at 5 ug/kg/min and titrated to maintain CO. Vigilance monitor, Edward Lifesciences, USA, was used to monitor cardiac output (CO) and systemic vascular resistance (SVR). The target was to keep CO above 4 L/min and SVR between 800 and 1200 dynes · sec/cmThe present case series describes successful anaesthetic management of patients having DCM and ESRD.Patients of DCM are on the verge of developing cardiac failure and patients of ESRD oscillate between hypovolemia and hypervolemia, so preoperative volume assessment is very important.Arrhythmias like ventricular tachyarrhythmias and atrial fibrillation are commonly associated with DCM . The risAnemia is a frequent finding in ESRD patients. Haemoglobin optimization is required for maintaining adequate oxygenation of the blood.Oxygen carrying capacity is also dependent on cardiac output (CO). To improve cardiac output inotropes may be utilized. In the event of failure of inotropes, biventricular synchronized pacing or an intra-aortic balloon pump may be required.Preoperative assessment  is imporIntraoperative Monitoring. Pulmonary artery catheterization and invasive arterial pressure monitoring are recommended in patients with left ventricular dysfunction undergoing renal transplantation [antation .maintenance of myocardial contractility,avoiding drug induced myocardial depression,prevention of increase in afterload,maintenance of adequate preload while preventing fluid overload,avoiding tachycardia,maintenance of adequate mean arterial pressure for renal perfusion,avoidance of nephrotoxic drugs.The goals of anaesthetic management are , 2mainteKidney transplantation is usually performed under general anaesthesia (GA) with endotracheal intubation and mechanical ventilation . GA provRegional anaesthesia was chosen over GA because it attenuates neurohumoral stress response to surgery, produces vasodilatation thereby decreasing afterload, decreases incidence of DVT, pulmonary embolism, and respiratory depression, avoids polypharmacy, decreases transfusion requirements, and is associated with early recovery . EpiduraCSE was preferred over continuous epidural technique, because spinal anaesthesia provides a reliable dense block and muscle relaxation to begin with and the duration of anaesthesia can be extended with epidural catheter. A low dose of bupivacaine heavy was given as low dose bupivacaine plus fentanyl has been shown to provide stable haemodynamics with reduced requirement of vasoconstrictive drugs or fluids . Sanatkaα2adrenoceptor agonist [Dexmedetomidine, a  agonist , infusio agonist . It has  agonist , 12 and The overall anesthetic goal for the newly transplanted kidney is to maintain intravascular volume and avoid decreased perfusion by maintaining MAP. Adequate volume expansion and a CVP of 10−15 mmHG are required . So our Hypotension should be avoided to prevent both myocardial and renal allograft hypoperfusion. To counteract the peripheral vasodilating effects of anaesthesia norepinephrine infusion was used to maintain adequate blood pressure . InotropThe postoperative period remained uneventful. All patients were discharged 15 to 20 days later with normal graft functions on oral immunosuppressants, antihypertensives, and oral hypoglycemics as required.The perioperative cardiovascular complication rate in renal transplant surgeries is 6% . DCM in Anesthetic management of a patient having dual problems of ESRD and DCMP is a challenge for the anaesthesiologist. The perioperative management of above patients teaches us that meticulous preoperative optimization, close intraoperative monitoring, tailoring the anaesthetic plan to patient's specific needs, optimization of fluid status and haemodynamics, and watchful postoperative care are the key to a successful renal transplant in these high risk patients.