Markers Of Organ Damage Research Articles

Role of Hemorrhagic Shock in Experimental Polytrauma.

Hemorrhagic shock (HS) after tissue trauma increases the complication and mortality rate of polytrauma (PT) patients. Although several murine trauma models have been introduced, there is a lack of knowledge about the exact impact of an additional HS. We hypothesized that HS significantly contributes to organ injury, which can be reliably monitored by detection of specific organ damage markers. Therefore we established a novel clinically relevant PT plus HS model in C57BL/6 mice which were randomly assigned to control, HS, PT, or PT+HS procedure (n = 8 per group). For induction of PT, anesthetized animals received a blunt chest trauma, head injury, femur fracture, and soft tissue injury. HS was induced by pressure-controlled blood drawing (mean arterial blood pressure of 30 mmHg for 60 min) and mice then resuscitated with ionosterile (4 × volume drawn), monitored, and killed for blood and organ harvesting 4 h after injury. After HS and resuscitation, PT+HS mice required earlier and overall more catecholamine support than HS animals to keep their mean arterial blood pressure. HS significantly contributed to the systemic release of interleukin-6 and high mobility group box 1 protein. Furthermore, the histological lung injury score, pulmonary edema, neutrophil influx, and plasma clara cell protein 16 were all significantly enhanced in PT animals in the presence of an additional HS. Although early morphological changes were minor, HS also contributed functionally to remote acute kidney injury but not to early liver damage. Moreover, PT-induced systemic endothelial injury, as determined by plasma syndecan-1 levels, was significantly aggravated by an additional HS. These results indicate that HS adds to the systemic inflammatory reaction early after PT. Within hours after PT, HS seems to aggravate pulmonary damage and to worsen renal and endothelial function which might overall contribute to the development of early multiple organ dysfunction.

Left ventricular hypertrophy and cognitive function: a systematic review.

Cognitive impairment is common in patients with hypertension. Left ventricular hypertrophy (LVH) is recognised as a marker of hypertension-related organ damage and is a strong predictor of coronary artery disease, heart failure and stroke. There is evidence that LVH is independently associated with cognitive impairment, even after adjustment for the presence of hypertension. We conducted a systematic review that examined cognitive impairment in adults with LVH. Independent searches were performed in Ovid MEDLINE, Ovid psycInfo and PubMed with the terms left ventricular hypertrophy and cognition. Seventy-three studies were identified when both searches were combined. After limiting the search to studies that were: (1) reported in English; (2) conducted in humans; (3) in adults aged 50 years and older; and (4) investigated the relationship between LVH and cognitive performance, nine papers were included in this systematic review. The majority of studies found an association between LVH and cognitive performance. Inspection of results indicated that individuals with LVH exhibited a lower performance in cognitive tests, when compared to individuals without LVH. Memory and executive functions were the cognitive domains that showed a specific vulnerability to the presence of LVH. A possible mechanism for the relationship between LVH and cognition is the presence of cerebral white matter damage. White matter lesions occur frequently in patients with LVH and may contribute to cognitive dysfunction. Together, the results of this review suggest that memory impairment and executive dysfunction are the cognitive domains that showed a particular association with the presence of LVH.

Is endocan a biochemical marker for asymptomatic target organ damage in hypertensive patients?

Objective:Identification of the asymptomatic target organ damage (AOD) helps to stratify the overall risk of cardiovascular (CV) diseases and guides a treatment decision in hypertensive patients without a symptomatic CV or renal disease. The endothelial-cell-specific molecule 1 (endocan) is regarded as a novel marker of endothelial dysfunction. Its release is increased in hypertensive patients, especially those with symptomatic CV and renal disease. In the present study, we aimed to evaluate the endocan levels in asymptomatic hypertensive patients with or without AOD.Methods:The study included 132 asymptomatic hypertensive patients, and 101 of who had at least one AOD.Results:Serum endocan levels did not differ between patients with and without AOD (3.81±0.78 vs. 3.83±0.63 ng/mL, p=0.88). An analysis according to the presence of any specific AOD did not show any difference between groups. No significant correlation was found between serum endocan levels and any of the continuous variables related to AOD, such as the pulse pressure, carotid intimae-media thickness, cardio-ankle vascular index, ankle-brachial index, left ventricular mass index, Sokolow–Lyon index, Cornell voltage-duration product, and estimated glomerular filtration rate.Conclusion:Endocan may not serve as a useful biomarker at asymptomatic vascular stages of hypertension, despite its role in indicating disease severity and inflammatory activation in advanced symptomatic CV and renal disease.

Usefulness of midregional pro-adrenomedullin as a marker of organ damage and predictor of mortality in patients with sepsis

BackgroundMidregional proadrenomedullin (MR-proADM) is a prognostic biomarker in patients with community-acquired pneumonia (CAP) and sepsis. In this paper, we examined the ability of MR-proADM to predict organ damage and long-term mortality in sepsis patients, compared to that of procalcitonin, C-reactive protein and lactate. MethodsThis was a prospective observational cohort, enrolling severe sepsis or septic shock patients admitted to internal service department. The association between biomarkers and 90-day mortality was assessed by Cox regression analysis and Kaplan–Meier curves. The accuracy of biomarkers for mortality was determined by area under the receiver operating characteristic curve (AUROC) analysis. ResultsA total of 148 patients with severe sepsis, according to the criteria of the campaign to survive sepsis, were enrolled. Eighty-five (57.4%) had sepsis according to the new criteria of Sepsis-3. MR-proADM showed the best AUROC to predict sepsis as defined by the Sepsis-3 criteria (AUROC of 0.771, 95% CI 0.692–0.850, p <0.001) and was the only marker independently associated with Sepsis-3 criteria (OR = 4.78, 95% CI 2.25–10.14; p < 0.001) in multivariate analysis.MR-proADM was the biomarker with the best AUROC to predict mortality in 90 days (AUROC of 0.731, CI 95% 0.612–0.850, p <0.001) and was the only marker that kept its independence [hazard ratio (HR) of 1.4, 95% CI 1.2-1.64, p <0.001] in multivariate analysis. The cut-off point of MR-proADM of 1.8 nmol/L (HR of 4.65, 95% CI 6.79–10.1, p < 0.001) was the one that had greater discriminative capacity to predict 90 days mortality. All patients with MR-proADM concentrations ≤0.60 nmol/L survived up to 90 days. In patients with SOFA ≤ 6, the addition of MR-proADM to SOFA score increased the ability of SOFA to identify non-survivors, AUROC of 0.65 (CI 95% 0.537–0.764) and AUROC of 0.700 (CI 95% 0.594–0.800), respectively (p < 0.05 for both). ConclusionsMR-proADM is a good biomarker in the early identification of high risk septic patients and may contribute to improve the predictive capacity of SOFA scale, especially when scores are low.

Higher pulse pressure and risk for cardiovascular events in patients with essential hypertension: The Campania Salute Network.

Background Increased pulse pressure is associated with structural target organ damage, especially in elderly patients, increasing cardiovascular risk. Design In this analysis, we investigated whether high pulse pressure retains a prognostic effect also when common markers of target organ damage are taken into account. Methods We analysed an unselected cohort of treated hypertensive patients from the Campania Salute Network registry ( n = 7336). Participants with available cardiac and carotid ultrasound were required to be free of prevalent cardiovascular disease, with ejection fraction ≥50%, and no more than stage III Chronic Kidney Disease. The median follow-up was 41 months and end-point was occurrence of major cardiovascular events (i.e. fatal and non-fatal stroke or myocardial infarction and sudden death). Based on current guidelines, pulse pressure ≥60 mm Hg was classified as high pulse pressure ( n = 2356), at the time of the initial visit, whereas pulse pressure <60 mm Hg was considered normal ( n = 4980). Results High pulse pressure patients were older, more likely to be women and diabetic, while receiving more antihypertensive medications than normal pulse pressure (all p < 0.0001). High pulse pressure exhibited greater prevalence of left ventricular hypertrophy, and carotid plaque than normal pulse pressure (all p < 0.0001). In Cox regression, high pulse pressure patients had 57% increased hazard of major cardiovascular events, compared to normal pulse pressure (hazard ratio = 1.57; 95% confidence interval: 1.12-2.22, p = 0.01), an effect that was independent of significant prognostic impact of older age, male sex, diabetes, left ventricular hypertrophy, carotid plaque and less prescription of anti-renin-angiotensin system therapy. Conclusions High pulse pressure is a functional marker of target organ damage, predicting cardiovascular events in hypertensive patients, even independently of well-known structural markers of target organ damage.

Results of the Randomized, Double-Blind, Placebo-Controlled, Phase 3 Hercules Study of Caplacizumab in Patients with Acquired Thrombotic Thrombocytopenic Purpura

Introduction: Acquired or immune-mediated thrombotic thrombocytopenic purpura (aTTP) is a life-threatening thrombotic microangiopathy characterized by severe thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia. Inhibitory autoantibodies cause a severe deficiency of the von Willebrand factor (vWF) cleaving enzyme ADAMTS13, leading to intravascular vWF-platelet aggregation and microvascular thrombosis. The mainstays of treatment are plasma exchange (PE) and immunosuppression. Caplacizumab, a bivalent Nanobody, targets the A1 domain of vWF, inhibiting the interaction between ultra-large vWF and platelets. Methods: Patients with an acute episode of aTTP who had received one PE treatment were randomized 1:1 to placebo or 10 mg caplacizumab, in addition to daily PE and corticosteroids. A single IV dose of study drug was given before the first on-study PE and a SC dose was given daily during the PE period and 30 days thereafter. If at the end of this period there was evidence of ongoing disease, such as suppressed ADAMTS13 activity, investigators were encouraged to extend the blinded treatment for a maximum of 4 weeks together with optimization of immunosuppression. All patients entered a 28-day treatment-free follow up period after the last dose of study drug (Figure 1). Primary endpoint was time to platelet count response, defined as platelet count ≥ 150×109/L with stop of daily PE within 5 days. There were 4 key secondary endpoints, hierarchically ranked. The 1st was a composite of aTTP-related death, aTTP recurrence, or major thromboembolic event during the study drug treatment period. A blinded, independent committee adjudicated aTTP-related deaths and major thromboembolic events. The 2nd looked at recurrences during the entire study period, including the follow up period. The 3d evaluated refractoriness to therapy, defined as absence of platelet count doubling after 4 days of treatment and LDH still above normal. The 4th was the time to normalization of 3 organ damage markers: LDH, cardiac troponin I and serum creatinine. Results: 145 patients were randomized, 73 to placebo and 72 to caplacizumab. Demographics and baseline disease characteristics were balanced between groups, except for a higher proportion of initial episodes in the caplacizumab arm. Compared to patients treated with placebo, those on caplacizumab were >50% more likely to achieve a platelet response at any given time point (platelet count normalization rate 1.55, 95% CI 1.10 - 2.20, p Conclusions: Results of the Phase 3 HERCULES study confirm that treatment with caplacizumab reduces the time to platelet count response, resulting in faster resolution of aTTP. Treatment with caplacizumab also resulted in a highly clinically meaningful reduction in aTTP-related death, recurrence of aTTP, or a major thromboembolic event during study drug treatment. The relapses after stop of study drug in patients with ADAMTS13 activity Disclosures Scully:Ablynx: Honoraria, Research Funding; Shire: Honoraria, Research Funding; Novartis: Honoraria; Alexion: Honoraria. Cataland:Ablynx NV: Membership on an entity9s Board of Directors or advisory committees. Peyvandi:Ablynx, Roche: Membership on an entity9s Board of Directors or advisory committees; Ablynx, Bayer, Grifols, Novo Nordisk, Sobi: Speakers Bureau;Freeline, Kedrion, LFB, Octapharma: Consultancy. Coppo:Ablynx: Membership on an entity9s Board of Directors or advisory committees; Alexion: Membership on an entity9s Board of Directors or advisory committees; Octapharma: Membership on an entity9s Board of Directors or advisory committees; Shire: Membership on an entity9s Board of Directors or advisory committees. Knobl:Novo Nordisk: Consultancy, Research Funding; Shire: Consultancy, Research Funding. Kremer Hovinga:Baxalta/Shire: Other: unrestricted grant hereditary TTP registry; Ablynx NV: Membership on an entity9s Board of Directors or advisory committees. Metjian:Ablynx NV, Shire, Omeros: Research Funding; Shire: Membership on an entity9s Board of Directors or advisory committees. de la Rubia:Amgen: Other: Honoraria; Celgene: Other: Honoraria; Janssen: Other: Honoraria. Pavenski:Alexion Pharmaceuticals: Honoraria; Novartis: Honoraria; Ablynx: Other: participation in industry sponsored RCT; CSL Behring: Research Funding. Callewaert:Ablynx NV: Employment. Biswas:Ablynx NV: Employment. De Winter:Ablynx NV: Employment. Zeldin:Ablynx NV: Employment.

Sexual dysfunction as a determinant of cardiovascular outcome in patients undergoing chronic hemodialysis.

Sexual dysfunction (SD) is common in men and women with chronic kidney disease (CKD) and is considered as an early marker for cardiovascular (CV) disease. We hypothesized that patients with SD have higher risk for vascular damage of the large arteries, accelerated vascular aging, and consequently higher CV mortality than other end-stage renal disease (ESRD) patients. In this study, the International Index of Erectile Function (IIEF) questionnaire and the Female Sexual Function Index (FSFI) questionnaire were applied in men and women, respectively. Ambulatory blood pressure monitoring (ABPM), arterial stiffness, and ankle-brachial index (ABI) were performed in all patients. Pulse wave velocity (PWV) was significantly slower in non-SD patients (10.5 vs. 8.8 m/s; p < 0.001) with significantly lower number of non-SD patients with PWV > 10 m/s compared to SD patients (p < 0.001). Only 57% of the patients with prior CV event had PWV > 10 m/s. No difference in AIx was observed. Non-SD patients had better values of ABI (0.83 vs. 1.09; p < 0.05) with significantly lower number of non-SD patients with ABI < 0.9 compared to SD patients (p = 0.001) as well as smaller percentage of LVH (57.5% vs. 80.7%; p = 0.01). There were no differences in hemodynamic parameters when patients with SD were divided by sex. Pulse wave velocity was the strongest predictor of lower IIEF and FSFI scores. Mean survival time was longer in non-SD patients than in SD patients (11.6 vs. 10.5 months, p = 0.019). The higher incidence of prior CV events and CV mortality found in SD patients on hemodialysis (HD) is a consequence of accelerated vascular aging. Sexual dysfunction in HD patients should also be considered a marker of subclinical organ damage and future CV events. Our study confirms the predictive role of PWV in HD patients.

The therapeutic value of protein (de)nitrosylation in experimental septic shock

Cardiovascular dysfunction and organ damage are hallmarks of sepsis and septic shock. Protein S-nitrosylation by nitric oxide has been described as an important modifier of protein function. We studied whether protein nitrosylation/denitrosylation would impact positively in hemodynamic parameters of septic rats. Polymicrobial sepsis was induced by cecal ligation and puncture. Female Wistar rats were treated with increasing doses of DTNB [5,5′-dithio-bis-(2-nitrobenzoic acid)] 30min before or 4 or 12h after sepsis induction. Twenty-four hours after surgery the following data was obtained: aorta response to phenylephrine, mean arterial pressure, vascular reactivity to phenylephrine, biochemical markers of organ damage, survival and aorta protein nitrosylation profile. Sepsis substantially decreases blood pressure and the response of aorta rings and of blood pressure to phenylephrine, as well as increased plasma levels of organ damage markers, mortality of 60% and S-nitrosylation of aorta proteins increased during sepsis. Treatment with DTNB 12h after septic shock induction reversed the loss of response of aorta rings and blood pressure to vasoconstrictors, reduced organ damage and protein nitrosylation and increased survival to 80%. Increases in protein S-nitrosylation are related to cardiovascular dysfunction and multiple organ injury during sepsis. Treatment of rats with DTNB reduced the excessive protein S-nitrosylation, including that in calcium-dependent potassium channels (BKCa), reversed the cardiovascular dysfunction, improved markers of organ dysfunction and glycemic profile and substantially reduced mortality. Since all these beneficial consequences were attained even if DTNB was administered after septic shock onset, protein (de)nitrosylation may be a suitable target for sepsis treatment.

Multiparametric analysis of anti-proliferative and apoptotic effects of gold nanoprisms on mouse and human primary and transformed cells, biodistribution and toxicity in vivo

BackgroundThe special physicochemical properties of gold nanoprisms make them very useful for biomedical applications including biosensing and cancer therapy. However, it is not clear how gold nanoprisms may affect cellular physiology including viability and other critical functions. We report a multiparametric investigation on the impact of gold-nanoprisms on mice and human, transformed and primary cells as well as tissue distribution and toxicity in vivo after parental injection.MethodsCellular uptake of the gold-nanoprisms (NPRs) and the most crucial parameters of cell fitness such as generation of reactive oxygen species (ROS), mitochondria membrane potential, cell morphology and apoptosis were systematically assayed in cells. Organ distribution and toxicity including inflammatory response were analysed in vivo in mice at 3 days or 4 months after parental administration.ResultsInternalized gold-nanoprisms have a significant impact in cell morphology, mitochondrial function and ROS production, which however do not affect the potential of cells to proliferate and form colonies. In vivo NPRs were only detected in spleen and liver at 3 days and 4 months after administration, which correlated with some changes in tissue architecture. However, the main serum biochemical markers of organ damage and inflammation (TNFα and IFNγ) remained unaltered even after 4 months. In addition, animals did not show any macroscopic sign of toxicity and remained healthy during all the study period.ConclusionOur data indicate that these gold-nanoprisms are neither cytotoxic nor cytostatic in transformed and primary cells, and suggest that extensive parameters should be analysed in different cell types to draw useful conclusions on nanomaterials safety. Moreover, although there is a tendency for the NPRs to accumulate in liver and spleen, there is no observable negative impact on animal health.

PP.06.10] BLOOD PRESSURE VARIABILITY AND TARGET ORGAN DAMAGE IN HYPERTENSION

Objective: Hypertension is associated with several markers of subclinical target organ damage (TOD). Short-term blood pressure variability (SBPV) is a prognostic factor for cardiovascular events in hypertensives. We hypothesized that there is a relationship between SBPV and TOD in never-treated hypertensives. Design and method: We enrolled 943 consecutive essential hypertensives (mean age 53 ± 12 years, 497 males). Markers of subclinical TOD [left ventricular mass index (LVMI), pulse wave velocity (PWV), total arterial compliance (TAC), ankle-brachial index (ABI) and estimated glomerular filtration rate (eGFR)] and 24-h ambulatory blood pressure were evaluated in all patients. LVMI was assessed echocardiographically using the Devereux formula. Carotid-femoral PWV was estimated with the Complior. eGFR was calculated by the Cockcroft-Gault formula. ABI was calculated by dividing the highest ankle systolic blood pressure by the highest brachial systolic blood pressure. The ratio of stroke volume to pulse pressure was measured echocardiographically as a surrogate of TAC. SBPV was calculated as follows: 1) SD of 24-hour, daytime, or nighttime SBP and 2) weighted SD of 24-hour SBP. Results: In multivariable regression analysis, all four variables of SBPV exhibited significant association with LVMI (p = 0.014, p = 0.002, p = 0.002 and p < 0.001, respectively), PWV (p = 0.021, p = 0.015, p = 0.055 and p = 0.006, respectively) and TAC (p = 0.048, p = 0.020, p = 0.036 and p = 0.006, respectively). In multivariable analysis, ABI and eGFR were not associated with indices of SBPV. We assessed TOD based on 2013 European Guidelines for Hypertension [left ventricular hypertrophy (LVMI>115 g/m2 in men and >95 g/m2 in women), increased PWV (PWV>10m/s), decreased ABI (ABI<0.9) and decreased renal function (eGFR<60 ml/min)]. In multivariable logistic regression analysis, SBPV indices were not associated with markers of TOD (P > 0.05). Conclusions: Our findings support a complex relationship between SBPV and TOD in hypertension. Specifically, SBPV is more closely related to markers of ventricular and vascular compliance than other markers of TOD in hypertension.

P3563The clinical significance pulse time index of norm as a marker of target organ damage

P3563The clinical significance pulse time index of norm as a marker of target organ damage

Adding markers of organ damage to risk score models improves cardiovascular risk assessment: Prospective analysis of a large cohort of adult outpatients

IntroductionGlobal cardiovascular (CV) risk stratification is recommended in all outpatients. Risk score charts, however, do not include markers of organ damage (OD). AimTo evaluate the potential added value of including different markers of subclinical OD to US Framingham, European SCORE and Italian Cuore risk score calculators. MethodsWe prospectively evaluated adult outpatients, who underwent blood pressure (BP) assessment and global CV risk stratification. The following OD markers were considered: 1) cardiac OD: electrocardiographic) or echocardiographic left ventricular (LV) hypertrophy; 2) vascular OD: carotid atherosclerotic plaque; 3) renal OD: reduced estimated glomerular filtration rate or creatinine clearance. Different risk score calculators were applied for comparisons. ResultsWe included an overall population sample of 1979 outpatients (44.0% female, age 57.2±13.0years, BMI 26,6±4,4kg/m2, clinic systolic/diastolic BP 145.4±18.3/85.8±10.7mmHg), among whom 117 (5.9%) presented cardiac, 161 (8.1%) vascular, and 117 (5.9%) renal OD. US Framingham, European SCORE and Italian Cuore risk scores were all significantly raised in patients with than in those without OD. A trend toward increase for US Framingham CVD death, European ESC and Italian Cuore scores was observed according to degree of all markers of OD. Among these, reduced ClCr and eGFR showed high sensitivity and specificity to identify high risk individuals. ConclusionsPresence of cardiac, vascular or renal OD is associated with higher risk scores, independently by the types of calculators, age and gender classes. OD detection should be included in CV risk stratification in order to improve diagnostic, prognostic and therapeutic processes.

Elevation of serum lactate dehydrogenase in AL amyloidosis reflects tissue damage and is an adverse prognostic marker in patients not eligible for stem cell transplantation.

The significance of serum lactate dehydrogenase (LDH) in light chain (AL) amyloidosis has not been previously explored. We studied 1019 newly diagnosed patients and correlated the elevation of LDH above the upper limit of normal (ULN) with disease characteristics and outcome. Four hundred and nine patients had an LDH above ULN, representing 40% of the study population. Patients with an elevated LDH were older, were less likely to be male and had more extensive organ involvement compared to patients with a normal LDH. Patients with high LDH had greater cardiac and renal dysfunction. Elevated LDH was an independent prognostic marker for overall survival and for death within 6months of diagnosis, but this was restricted to patients not eligible for stem cell transplant. Serum LDH may act as a marker for organ damage and should be explored as a potential marker for tissue healing and organ recovery.

Attitudes and preferences for the clinical management of hypertension and hypertension-related cerebrovascular disease in the general practice: results of the Italian hypertension and brain survey

BackgroundThe aim of this survey was to evaluate attitudes and preferences for the clinical management of hypertension and hypertension-related cerebrovascular diseases (CVD) in Italy.MethodsA predefined 16-item survey questionnaire was anonymously administered to a large community sample of general practitioners (GPs), trained by specialized physicians (SPs), who have been included in an educational program between January and November 2015. ResultsA total of 591 physicians, among whom 48 (8%) training SPs and 543 (92%) trained GPs, provided 12,258 valid answers to the survey questionnaire. Left ventricular hypertrophy was considered the most frequent marker of hypertension-related organ damage, whereas atrial fibrillation and carotid atherosclerosis were considered relatively not frequent (10–20%). The most appropriate blood pressure (BP) targets to be achieved in hypertensive patients with CVD were <140/90 mmHg for SPs and <135/85 mmHg for GPs. To achieve these goals, ACE inhibitors were considered the most effective strategies by GPs, whereas SPs expressed a preference for ARBs, both in monotherapies and in combination therapies with beta-blockers.ConclusionsThis survey demonstrates that Italian physicians considered left ventricular hypertrophy frequently associated to CVD and that drugs inhibiting the renin-angiotensin system the most appropriate therapy to manage hypertension and hypertension-related CVD.

Changes in albumin-to-creatinine ratio at 12-month follow-up in patients undergoing renal denervation

IntroductionSympathetic renal denervation (RDN) was developed as a treatment for the management of patients with resistant hypertension. This procedure may have a positive impact on hypertension-related target organ damage, particularly renal disease, but the evidence is still limited. ObjectiveTo assess the impact of RDN on the albumin-to-creatinine ratio (ACR) at 12-month follow-up. Methods and ResultsFrom a single-center prospective registry including 65 patients with resistant hypertension undergoing renal denervation, 31 patients with complete baseline and 12-month follow-up blood pressure (BP) measurements (both office and 24-h ambulatory blood pressure monitoring [ABPM]) and ACR were included in the present study. Mean age was 65±7 years, 52% were female, most (90%) had been diagnosed with hypertension for more than 10 years, 71% had type 2 diabetes and 33% had vascular disease in at least one territory. Mean estimated glomerular filtration rate was 73.6±25.1 ml/min/1.73 m2 and 15 patients (48%) had an ACR >30 mg/g. After 12 months, 22 patients were considered BP responders (73%). ACR decreased significantly from a median of 25.8 mg/g (interquartile range [IQR] 9.0-574.0 mg/g) to 14.8 mg/g (IQR 4.5-61.0 mg/g, p=0.007). When the results were split according to systolic BP responder status on ABPM, we found a significant reduction in responders (from 25.6 mg/g [IQR 8.7-382.8 mg/g] to 15.9 mg/g [IQR 4.4-55.0 mg/g], p=0.009), and a numerical decrease in the non-responder subgroup (from 165.0 mg/g [IQR 8.8-1423.5 mg/g] to 13.6 mg/dl [IQR 5.7-1417.0 mg/g], p=0.345). ConclusionsBesides significant reductions in blood pressure (both office and 24-h ABPM), renal denervation was associated with a significant reduction in ACR, a recognized marker of target organ damage.

Monitoring Cardiovascular, Hepatic, Renal, And Hematological Markers Of Health In Collegiate Soccer Players

Clinical biomarkers of general health status may indicate health impacts of overtraining in athletes attempting to optimize performance using long-term tracking tools. PURPOSE: To test the hypothesis that biomarkers of cardiovascular, liver, kidney and hematological function reflect athlete health and performance over the course of a collegiate soccer season. METHODS: 20 NCAA Division I male soccer players (mean±SD; height, 181±6cm; body mass, 77.9±6.2kg; BF%, 11.9±2.4%; VO2max, 52.9±6.1 mL[BULLET OPERATOR]kg[BULLET OPERATOR]min-1) provided blood samples for a test panel of 53 biomarkers at 5 time points: before preseason (PS), week 1 (W1), week 4 (W4), week 8 (W8), and week 12 (W12). Significant changes were assessed via repeated measures ANOVA and post hoc testing (p≤0.05). RESULTS: Markers of potential organ damage markers aspartate amino transferase (AST) (U[BULLET OPERATOR]L-1) and creatinine (mg[BULLET OPERATOR]dL-1) were elevated at W1 (AST, creatinine; 29±11, 1.11±0.13), W8 (31±11, 1.11±0.11), and W12 (28±11, 1.15±0.13) vs. PS (18±4, 1.02±0.13, all p<0.05). Alanine amino transferase (ALT) (U[BULLET OPERATOR]L-1) levels were also significantly higher at W8 (24±8) and W12 (24±9) vs. PS (18±5, both p<0.05). Hematocrit (%) measures were significantly reduced at W1 (45.5±2.3, p=0.015) vs. PS (47.2±2.8); W4 (46.4±2.6) and W12 (46.4±3.1) values suggest that values returned to PS levels (p>0.05) later in season. Additional markers of anemia, mean corpuscular volume, mean corpuscular hemoglobin concentration, red cell distribution width were reduced at W12 vs. all time points (all p<0.007). We observed reductions in cardiovascular/metabolic health markers (mg[BULLET OPERATOR]dL-1) LDL, LDL:HDL (no unit), non-HDL, direct LDL, and Apolipoprotein B at W1 (77±20, 3.2±0.5, 106±24, 96±25, and 71±17) than at PS (87±22, 2.8±0.5, 93±22, 81±22, and 64±15, all p<0.017). HDL (mg[BULLET OPERATOR]dL-1) was significantly greater at W4 (56±10), W8 (55±10), and W12 (58±11) than at PS (50±8, all p<0.05). Total cholesterol (mg[BULLET OPERATOR]dL-1) was significantly elevated at W8 (163±28, p=0.012) and W12 (168±31, p=0.007) vs. W1 (145± 26). CONCLUSIONS: Our panel detected a decrease in HCT beginning at W1, but improved cardiovascular/metabolic health throughout the season. Ongoing analysis aims to optimize this general health panel for practical use by correlational analysis to performance data.

Changes in albumin-to-creatinine ratio at 12-month follow-up in patients undergoing renal denervation

IntroductionSympathetic renal denervation (RDN) was developed as a treatment for the management of patients with resistant hypertension. This procedure may have a positive impact on hypertension-related target organ damage, particularly renal disease, but the evidence is still limited. ObjectiveTo assess the impact of RDN on the albumin-to-creatinine ratio (ACR) at 12-month follow-up. Methods and ResultsFrom a single-center prospective registry including 65 patients with resistant hypertension undergoing renal denervation, 31 patients with complete baseline and 12-month follow-up blood pressure (BP) measurements (both office and 24-h ambulatory blood pressure monitoring [ABPM]) and ACR were included in the present study. Mean age was 65±7 years, 52% were female, most (90%) had been diagnosed with hypertension for more than 10 years, 71% had type 2 diabetes and 33% had vascular disease in at least one territory. Mean estimated glomerular filtration rate was 73.6±25.1 ml/min/1.73 m2 and 15 patients (48%) had an ACR >30 mg/g. After 12 months, 22 patients were considered BP responders (73%). ACR decreased significantly from a median of 25.8 mg/g (interquartile range [IQR] 9.0-574.0 mg/g) to 14.8 mg/g (IQR 4.5-61.0 mg/g, p=0.007). When the results were split according to systolic BP responder status on ABPM, we found a significant reduction in responders (from 25.6 mg/g [IQR 8.7-382.8 mg/g] to 15.9 mg/g [IQR 4.4-55.0 mg/g], p=0.009), and a numerical decrease in the non-responder subgroup (from 165.0 mg/g [IQR 8.8-1423.5 mg/g] to 13.6 mg/dl [IQR 5.7-1417.0 mg/g], p=0.345). ConclusionsBesides significant reductions in blood pressure (both office and 24-h ABPM), renal denervation was associated with a significant reduction in ACR, a recognized marker of target organ damage.

Assessment of Early Cardiovascular Risk in Children and Adolescents with Essential Hypertension.

The aim of our study was to investigate some early markers of hypertensive target organ damage in hypertensive children and adolescents, and to detect those showing most prominent clinical significance. We included 100 children with essential hypertension (EH) and 50 age-matched healthy control children, and evaluated left ventricular mass (LVM), intima-media thickness in the carotid arteries (IMT), pulse wave velocity (PWV), microalbuminuria, biochemical parameters and some adipokines. Statistically significant differences between the 2 groups were observed for HDL-cholesterol, LDL-cholesterol, triglycerides, insulin, uric acid, glucose, apolipoprotein A1, and total adiponectin. The mean values of IMT, PWV and LVM were greater in hypertensive children, but only the differences in IMT and LVM were statistically significant. In addition, hypertensive children showed significantly higher values of AoSP (aortic systolic pressure), AoPP (aortic pulse pressure) and AIx@75 (augmentation index corrected for heart rate of 75 b.p.m.). Metabolic syndrome was diagnosed in 31% of hypertensive children. A significant number of children with EH have early target organ changes as well as other risk factors, including metabolic syndrome, especially obese ones. However, IMT, LVM and some parameters of arterial stiffness have been found to be early markers in both obese and non-obese hypertensives. In addition, adipokines and coagulation factors seem to be important in obese hypertensives.

Rapid DNA vaccination against Burkholderia pseudomallei flagellin by tattoo or intranasal application

ABSTRACT Melioidosis is a severe infectious disease with a high mortality that is endemic in South-East Asia and Northern Australia. The causative pathogen, Burkholderia pseudomallei, is listed as potential bioterror weapon due to its high virulence and potential for easy dissemination. Currently, there is no licensed vaccine for prevention of melioidosis. Here, we explore the use of rapid plasmid DNA vaccination against B. pseudomallei flagellin for protection against respiratory challenge. We tested three flagellin DNA vaccines with different subcellular targeting designs. C57BL/6 mice were vaccinated via skin tattoo on day 0, 3 and 6 before intranasal challenge with B. pseudomallei on day 21. Next, the most effective construct was used as single vaccination on day 0 by tattoo or intranasal formulation. Mice were sacrificed 72 hours post-challenge to assess bacterial loads, cytokine responses, inflammation and microscopic lesions. A construct encoding a cellular secretion signal resulted in the most effective protection against melioidosis via tattooing, with a 10-fold reduction in bacterial loads in lungs and distant organs compared to the empty vector. Strikingly, a single intranasal administration of the same vaccine resulted in >1000-fold lower bacterial loads and increased survival. Pro-inflammatory cytokine responses were significantly diminished and strong reductions in markers for distant organ damage were observed. A rapid vaccination scheme using flagellin DNA tattoo provides significant protection against intranasal challenge with B. pseudomallei, markedly improved by a single administration via airway mucosa. Hence intranasal vaccination with flagellin-encoding DNA may be applicable when acute mass vaccination is indicated and warrants further testing.

How to Measure 24-hour Central Blood Pressure and Its Potential Clinical Implications

The evaluation of 24-hour central blood pressure (24h cBP) combines the cBP non-invasive assessment with the 24-h ambulatory BP measurement. The major strength of the 24-h cBP evaluation is the ability to assess the degree of circadian changes between central and peripheral BP, namely 24-h BP amplification. This allows an accurate quantification of the degree of spatial and temporal BP variability in each single individual. BP amplification depends from a number of factors, such as the interaction between pressure and flow pulsatile motions, vasomotor tone, arterial tapering and other physiological and anthropometrical determinants. The assessment of 24-h BP amplification, a relatively pressure-independent parameter, may be helpful in better refining the risk of organ damage and future CV events over traditional measures of office and 24-h brachial BP. Currently, only few devices enable the assessment of 24-h cBP. These devices are based on peripheral (brachial or radial) BP waveform detection, and reconstruction of central BP waveform through mathematical models. The estimation of 24-h cBP imputed from multivariate regression equations was also proposed. Clinical data are still scarce and, although suggesting a possible superiority of 24-h cBP over brachial BP in the association with markers of organ damage, they are limited by methodological and technical aspects. There is urgent need of a standardized methodology and rigorous validation protocols for the 24-h cBP assessment. The field of 24-h cBP measurement still requires significant advancements of scientific knowledge before its introduction into clinical practice.