Expression of a2 Vacuolar ATPase in Spermatozoa is Associated with Semen Quality and Chemokine-Cytokine Profiles in Infertile Men

Background

A number of laboratory tests have been developed to determine properties of spermatozoa quality but few have been adopted into routine clinical use in place of the WHO semen analysis. We investigated whether Atp6v0a2 (a2 isoform of vacuolar ATPase) is associated with abnormal semen quality and changes in chemokine-cytokine profiles in infertile men.

Patients and Methods

Semen samples were collected from 35 healthy donors and 35 infertile men at the Andrology laboratory from August 2011 to June 2012. The levels of Atp6v0a2 mRNA and protein, and its localization in spermatozoa were determined. a2NTD (the N-terminal portion of Atp6v0a2) and secreted chemokine-cytokine profiles in seminal fluid were measured.

Results

Atp6v0a2 protein (P<0.05) and mRNA (P<0.05) in spermatozoa from infertile men were significantly lower than those from fertile men. Fluorescent microscopy revealed that Atp6v0a2 is mainly expressed in the acrosomal region. Infertile men’s seminal fluid had significantly lower G-CSF (P<0.01), GM-CSF (P<0.01), MCP-1 (P<0.05), MIP-1α (P<0.01) and TGF-β1 (P<0.01) levels when compared to the seminal fluid from fertile men. Seminal fluid a2NTD levels were significantly correlated with G-CSF (P<0.01), GM-CSF (P<0.01), MCP-1 (P<0.05), MIP-1α (P<0.01) and TGF-β1 (P<0.01) which are key molecules during the onset of pregnancy.

Conclusion

These results suggested that a critical level of Atp6v0a2 is required for the fertile spermatozoa and its decreased level in spermatozoa could be used to predict male infertility. This study provides a possibility that Atp6v0a2 could be potentially used as a diagnostic marker for the evaluation of male infertility.     

The Predictive Value of the Boston Acute Stroke Imaging Scale (BASIS) in Acute Ischemic Stroke Patients among Chinese Population

Objective

Evaluate the predictive value of Boston Acute Stroke Imaging Scale (BASIS) in acute ischemic stroke in Chinese population.

Methods

This was a retrospective study. 566 patients of acute ischemic stroke were classified as having a major stroke or minor stroke based on BASIS. We compared short-term outcome (death, occurrence of complications, admission to intensive care unit [ICU] or neurological intensive care unit [NICU]), long-term outcome (death, recurrence of stroke, myocardial infarction, modified Rankin scale) and economic index including in-hospital cost and length of hospitalization. Continuous variables were compared by using the Student t test or Kruskal-Wallis test. Categorical variables were tested with the Chisquare test. Cox regression analysis was applied to identify whether BASIS was the independent predictive variable of death.

Results

During hospitalization, 9 patients (4.6%) died in major stroke group while no patients died in minor stroke group (p<0.001), 12 patients in the major stroke group and 5 patients in minor stroke group were admitted to ICU/NICU (p = 0.001). There were more complications (cerebral hernia, pneumonia, urinary tract infection) in major stroke group than minor stroke group (p<0.05). Meanwhile, the average cost of hospitalization in major stroke group was 3,100 US$ and 1,740 US$ in minor stroke group (p<0.001); the average length of stay in major and minor stroke group was 21.3 days and 17.3 days respectively (p<0.001). Results of the follow-up showed that 52 patients (26.7%) died in major stroke group while 56 patients (15.1%) died in minor stroke group (P<0.001). 62.2% of the patients in major stroke group and 80.4% of the patients in minor stroke group were able to live independently (P = 0.002). The survival analysis showed that patients with major stroke had 80% higher of risk of death than patients with minor stroke even after adjusting traditional atherosclerotic factors and NIHSS at baseline (HR = 1.8, 95% CI: 1.1–3.1).

Conclusion

BASIS can predict in-hospital mortality, occurrence of complication, length of stay and hospitalization cost of the acute ischemic stroke patients and can also estimate the long term outcome (death and the dependency). BASIS could and should be used as a dichotomous stroke classification system in the daily practice.     

Sodium Bicarbonate Treatment during Transient or Sustained Lactic Acidemia in Normoxic and Normotensive Rats

Introduction

Lactic acidosis is a frequent cause of poor outcome in the intensive care settings. We set up an experimental model of lactic acid infusion in normoxic and normotensive rats to investigate the systemic effects of lactic acidemia per se without the confounding factor of an underlying organic cause of acidosis.

Methodology

Sprague Dawley rats underwent a primed endovenous infusion of L(+) lactic acid during general anesthesia. Normoxic and normotensive animals were then randomized to the following study groups (n = 8 per group): S) sustained infusion of lactic acid, S+B) sustained infusion+sodium bicarbonate, T) transient infusion, T+B transient infusion+sodium bicarbonate. Hemodynamic, respiratory and acid-base parameters were measured over time. Lactate pharmacokinetics and muscle phosphofructokinase enzyme''s activity were also measured.

Principal Findings

Following lactic acid infusion blood lactate rose (P<0.05), pH (P<0.05) and strong ion difference (P<0.05) drop. Some rats developed hemodynamic instability during the primed infusion of lactic acid. In the normoxic and normotensive animals bicarbonate treatment normalized pH during sustained infusion of lactic acid (from 7.22±0.02 to 7.36±0.04, P<0.05) while overshoot to alkalemic values when the infusion was transient (from 7.24±0.01 to 7.53±0.03, P<0.05). When acid load was interrupted bicarbonate infusion affected lactate wash-out kinetics (P<0.05) so that blood lactate was higher (2.9±1 mmol/l vs. 1.0±0.2, P<0.05, group T vs. T+B respectively). The activity of phosphofructokinase enzyme was correlated with blood pH (R2 = 0.475, P<0.05).

Conclusions

pH decreased with acid infusion and rose with bicarbonate administration but the effects of bicarbonate infusion on pH differed under a persistent or transient acid load. Alkalization affected the rate of lactate disposal during the transient acid load.     

Supratentorial Gliomas in Eloquent Areas: Which Parameters Can Predict Functional Outcome and Extent of Resection?

Background

To date, few parameters have been found that can aid in patient selection and surgical strategy for eloquent area gliomas.

Aims

The aim of the study was to analyze preoperative and intraoperative factors that can predict functional outcome and extent of resection in eloquent area tumors.

Patients and Methods

A retrospective analysis was conducted on 60 patients harboring supratentorial gliomas in eloquent areas undergoing awake surgery. The analysis considered clinical, neuroradiologic (morphologic), intraoperative, and postoperative factors. End-points were extent of resection (EOR) as well as functional short- and long-term outcome. Postoperatively, MRI objectively established the EOR. χ² analyses were used to evaluate parameters that could be predictive. Multivariate logistic regression analyses were used to evaluate the best combination to predict binary positive outcomes.

Results

In 90% of the cases, subcortical stimulation was positive in the margins of the surgical cavity. Postoperatively, 51% of the patients deteriorated but 90% of the patients regained their preoperative neurological score. Factors negatively affecting EOR were volume, degree of subcortical infiltration, and presence of paresis (P<0.01). Sharp margins and cystic components were more amenable to gross total resection (P<0.01). Contrast enhancement (P<0.02), higher grade (P<0.01), paresis (P<0.01), and residual tumor in the cortex (P<0.02) negatively affected long-term functional outcomes, whereas postoperative deterioration could not be predicted for any factor other than paresis. Subcortical stimulation did not correlate with deterioration, both postoperatively (P<0.08) and at follow-up (P<0.042).

Conclusions

Biological and morphological factors such as type of margins, volume, preoperative neurological status, cystic components, histology and the type of infiltration into the white matter must be considered when planning intraoperative mapping.     

Altered Mitochondrial Function and Oxidative Stress in Leukocytes of Anorexia Nervosa Patients

Context

Anorexia nervosa is a common illness among adolescents and is characterised by oxidative stress.

Objective

The effects of anorexia on mitochondrial function and redox state in leukocytes from anorexic subjects were evaluated.

Design and setting

A multi-centre, cross-sectional case-control study was performed.

Patients

Our study population consisted of 20 anorexic patients and 20 age-matched controls, all of which were Caucasian women.

Main outcome measures

Anthropometric and metabolic parameters were evaluated in the study population. To assess whether anorexia nervosa affects mitochondrial function and redox state in leukocytes of anorexic patients, we measured mitochondrial oxygen consumption, membrane potential, reactive oxygen species production, glutathione levels, mitochondrial mass, and complex I and III activity in polymorphonuclear cells.

Results

Mitochondrial function was impaired in the leukocytes of the anorexic patients. This was evident in a decrease in mitochondrial O₂ consumption (P<0.05), mitochondrial membrane potential (P<0.01) and GSH levels (P<0.05), and an increase in ROS production (P<0.05) with respect to control subjects. Furthermore, a reduction of mitochondrial mass was detected in leukocytes of the anorexic patients (P<0.05), while the activity of mitochondrial complex I (P<0.001), but not that of complex III, was found to be inhibited in the same population.

Conclusions

Oxidative stress is produced in the leukocytes of anorexic patients and is closely related to mitochondrial dysfunction. Our results lead us to propose that the oxidative stress that occurs in anorexia takes place at mitochondrial complex I. Future research concerning mitochondrial dysfunction and oxidative stress should aim to determine the physiological mechanism involved in this effect and the physiological impact of anorexia.     

Compromised Dynamic Cerebral Autoregulation in Patients with a Right-to-Left Shunt: A Potential Mechanism of Migraine and Cryptogenic Stroke

Background and Purpose

The relationship between right-to-left shunts (RLS) and migraine and cryptogenic stroke is not well understood. In this study, we investigated whether RLS are associated with impairment of dynamic cerebral autoregulation (dCA), which may play a role in migraine and cryptogenic stroke.

Methods

Sixty-six migraineurs were enrolled in the study, including 36 non-RLS patients and 30 RLS patients. Non-invasive continuous cerebral blood flow velocity and arterial blood pressure were recorded simultaneously from each patient by using transcranial Doppler and servo-controlled plethysmograph, respectively. Transfer function analysis was applied to derive autoregulatory parameters of gain, phase difference (PD), and autoregulation index.

Results

The PD in migraineurs with RLS was 50.6±22.9 degrees, which was significantly lower than that observed in the non-RLS group (67.2±18.2 degrees, P<0.001). The PD in the large RLS group (45.4±22.6 degrees) was significantly lower than that of the small RLS group (64.9±17.1 degrees, P<0.01) and non-RLS group (P<0.001); however, the PD in the small RLS group was similar to that of the non-RLS group. The PD in the permanent group (48.8±19.9 degrees) was similar to that of the latent group (52.6±26.1 degrees), and both were significantly lower than that of the non-RLS group (P<0.05). The autoregulation index results were similar to the PD findings.

Conclusions

dCA is impaired in migraineurs with large RLS, and this may represent a potential mechanism linking RLS, migraine, and cryptogenic stroke.     

Stroke Code Improves Intravenous Thrombolysis Administration in Acute Ischemic Stroke

Background and Purpose

Timely intravenous (IV) thrombolysis for acute ischemic stroke is associated with better clinical outcomes. Acute stroke care implemented with “Stroke Code” (SC) may increase IV tissue plasminogen activator (tPA) administration. The present study aimed to investigate the impact of SC on thrombolysis.

Methods

The study period was divided into the “pre-SC era” (January 2006 to July 2010) and “SC era” (August 2010 to July 2013). Demographics, critical times (stroke symptom onset, presentation to the emergency department, neuroimaging, thrombolysis), stroke severity, and clinical outcomes were recorded and compared between the two eras.

Results

During the study period, 5957 patients with acute ischemic stroke were admitted; of these, 1301 (21.8%) arrived at the emergency department within 3 h of stroke onset and 307 (5.2%) received IV-tPA. The number and frequency of IV-tPA treatments for patients with an onset-to-door time of <3 h increased from the pre-SC era (n = 91, 13.9%) to the SC era (n = 216, 33.3%) (P<0.001). SC also improved the efficiency of IV-tPA administration; the median door-to-needle time decreased (88 to 51 min, P<0.001) and the percentage of door-to-needle times ≤60 min increased (14.3% to 71.3%, P<0.001). The SC era group tended to have more patients with good outcome (modified Rankin Scale ≤2) at discharge (49.5 vs. 39.6%, P = 0.11), with no difference in symptomatic hemorrhage events or in-hospital mortality.

Conclusion

The SC protocol increases the percentage of acute ischemic stroke patients receiving IV-tPA and decreases door-to-needle time.     

Meta-Analysis of Randomized Controlled Trials Comparing Latanoprost with Timolol in the Treatment of Asian Populations with Chronic Angle-Closure Glaucoma

Background

To evaluate the efficacy and safety of latanoprost compared with timolol in the treatment of Asian patients with chronic angle-closure glaucoma (CACG).

Methods

Relevant trials were identified through systematic searches of Medline, EMBASE, PubMed, Cochrane Library, Google Scholar and several Chinese databases. The main outcome measures included absolute and relative reduction of intraocular pressure (IOP) at mean, peak and trough from baseline, ocular adverse effects and systemic adverse events.

Results

Seven randomized controlled trials with 685 patients were included. In comparison with timolol, latanoprost reduced absolute IOP in CACG patients by more than 2.3 mmHg (95%CI, 1.8∼2.9, P<0.01), 2.4 mmHg (95%CI, 1.9∼2.9, P<0.01) and 2.5 mmHg (95%CI, 1.6∼3.3, P<0.01) at mean, peak and trough, respectively. As for relative IOP, there is 9.0% (95%CI, 6.6∼11.4, P<0.01), 9.7% (95%CI, 7.6∼11.8, P<0.01), and 10.8% (95%CI, 7.4∼14.3, P<0.01) greater reduction among latanoprost users than among timolol users. The differences were statistically significant at all time points (1, 2, 4, 8, 12, and 24 weeks). More ocular adverse effects (OR = 1.49, 95% CI, 1.05∼2.10, P = 0.02) and less systemic adverse events (OR = 0.46, 95% CI, 0.25∼0.84, P = 0.01) were observed in latanoprost group in comparison with timolol group.

Conclusion

Compared with timolol, latanoprost was significantly more effective in lowering IOP of Asian patients with CACG, with higher risk of ocular adverse effects but lower risk of systemic adverse events, and might be a good substitute for CACG patients.     

Soluble Tumor Necrosis Factor Related Apoptosis Inducing Ligand Level as a Predictor of Severity of Sepsis and the Risk of Mortality in Septic Patients

Background

Tumor necrosis factor related apoptosis inducing ligand (TRAIL) as a member of the TNF gene superfamily induces apoptosis primarily in tumor cells. TRAIL also plays an important role in the modulation of inflammatory responses, especially in the process of immune paralysis. The aim of the present study was to examine soluble TRAIL (sTRAIL) levels in septic patients in an attempt to explore the association between sTRAIL level and the risk of mortality.

Methods

Plasma sTRAIL levels were detected by ELISA in 50 septic patients and 20 healthy volunteers. HLA-DR expression in monocytes was detected by flow cytometry. Selective biochemical parameters were recorded, and patients were monitored in a 28-day period for mortality.

Results

The mean plasma sTRAIL level in septic patients was significantly lower than that in healthy controls (16.9±8.3 vs. 68.3±8.6 pg/ml, P<0.01), and was significantly higher in 28-day survivors than those in non-survivors (19.4±9.8 vs. 13.9±4.7 pg/ml, P<0.05). Univariate analysis indicated that plasma sTRAIL level was positively correlated with monocyte and lymphocyte counts and HLA-DR expression level (r = 0.5, P<0.01; r = 0.3, P<0.05; r = 0.43, P<0.01, respectively). STRAIL level was negatively correlated with APACHE II score, BUN and age (r = −0.48, P<0.01; r = −0.29, P<0.05; r = −0.45, P<0.01, respectively). Multiple linear regression analysis indicated that the predictor of plasma soluble TRAIL level was HLA-DR expression (P<0.01).

Conclusion

Low plasma sTRAIL levels were associated with immune paralysis and a high risk of mortality in patients with septic shock. sTRAIL may prove to be a potential biomarker of immune function and predict the survival of septic patients.     

Effects of Body Mass Index on Risks for Ischemic Stroke,Thromboembolism, and Mortality in Chinese Atrial Fibrillation Patients: A Single-Center Experience

Background

Obesity is considered to be related to recurrence of atrial fibrillation (AF), left atrial thrombus formation, and atrial remodeling. However, whether obesity is an independent risk factor for stroke and other thromboembolic events is still controversial.

Objective

This study aimed to investigate the effects of body mass index (BMI) on the risks of stroke, thromboembolism, and mortality in AF patients.

Methods

Patients who were diagnosed with nonvalvular AF were included in this observational, retrospective study. The study population was stratified by BMI at baseline. The Cox proportional hazard model was adopted to calculate adjusted hazard ratios of risk factors for adverse clinical events (stroke, thromboembolism, and mortality).

Results

A total of 1286 AF patients (males, 78.30%; mean age, 74.50 years; 94.48% paroxysmal AF) were followed up for a median of 2.1 years (IQR: 1.5–2.9 years). Overall, 159 patients died. A total of 84 strokes and 35 thromboembolic events occurred. Multivariate analysis showed that overweight (25.0≤BMI<30.0 kg/m²) and age ≥75 years were independent risk factors for ischemic stroke (both P<0.01). Obesity (BMI ≥30.0 kg/m²), age ≥75 years, persistent/permanent AF, and prior thromboembolism were independent risk factors for thromboembolism (all P<0.05). Underweight (BMI <18.5 kg/m²), age ≥75 years, prior ischemic stroke/transient ischemic attack, renal dysfunction, and heart failure were independent risk factors for all-cause deaths (all P<0.05).

Conclusions

Overweight or obesity may be a risk factor of ischemic stroke and thromboembolism in AF patients. Excessive low weight is significantly associated with increased all-cause mortality.     

Post-Stroke Epilepsy in Young Adults: A Long-Term Follow-Up Study

Background

Little is known about the incidence and risk of seizures after stroke in young adults. Especially in the young seizures might dramatically influence prognosis and quality of life. We therefore investigated the long-term incidence and risk of post-stroke epilepsy in young adults with a transient ischemic attack (TIA), ischemic stroke (IS) or intracerebral hemorrhage (ICH).

Methods and Findings

We performed a prospective cohort study among 697 consecutive patients with a first-ever TIA, IS or ICH, aged 18–50 years, admitted to our hospital between 1-1-1980 till 1-11-2010. The occurrence of epilepsy was assessed by standardized questionnaires and verified by a neurologist. Cumulative risks were estimated with Kaplan-Meier analysis. Cox proportional hazard models were used to calculate relative risks. After mean follow-up of 9.1 years (SD 8.2), 79 (11.3%) patients developed post-stroke epilepsy and 39 patients (5.6%) developed epilepsy with recurrent seizures. Patients with an initial late seizure more often developed recurrent seizures than patients with an initial early seizure. Cumulative risk of epilepsy was 31%, 16% and 5% for patients with an ICH, IS and TIA respectively (Logrank test ICH and IS versus TIA p<0.001). Cumulative risk of epilepsy with recurrent seizures was 23%, 8% and 4% respectively (Logrank ICH versus IS p = 0.05, ICH versus TIA p<0.001, IS versus TIA p = 0.01). In addition a high NIHSS was a significant predictor of both epilepsy and epilepsy with recurrent seizures (HR 1.07, 95% CI 1.03–1.11 and 1.08, 95% CI 1.02–1.14).

Conclusions

Post-stroke epilepsy is much more common than previously thought. Especially patients with an ICH and a high NIHSS are at high risk. This calls upon the question whether a subgroup could be identified which benefits from the use of prophylactic antiepileptic medication. Future studies should be executed to investigate risk factors and the effect of post-stroke epilepsy on quality of life.     

Novel Cell-Free Strategy for Therapeutic Angiogenesis: In Vitro Generated Conditioned Medium Can Replace Progenitor Cell Transplantation

Background

Current evidence suggests that endothelial progenitor cells (EPC) contribute to ischemic tissue repair by both secretion of paracrine factors and incorporation into developing vessels. We tested the hypothesis that cell-free administration of paracrine factors secreted by cultured EPC may achieve an angiogenic effect equivalent to cell therapy.

Methodology/Principal Findings

EPC-derived conditioned medium (EPC-CM) was obtained from culture expanded EPC subjected to 72 hours of hypoxia. In vitro, EPC-CM significantly inhibited apoptosis of mature endothelial cells and promoted angiogenesis in a rat aortic ring assay. The therapeutic potential of EPC-CM as compared to EPC transplantation was evaluated in a rat model of chronic hindlimb ischemia. Serial intramuscular injections of EPC-CM and EPC both significantly increased hindlimb blood flow assessed by laser Doppler (81.2±2.9% and 83.7±3.0% vs. 53.5±2.4% of normal, P<0.01) and improved muscle performance. A significantly increased capillary density (1.62±0.03 and 1.68±0.05/muscle fiber, P<0.05), enhanced vascular maturation (8.6±0.3 and 8.1±0.4/HPF, P<0.05) and muscle viability corroborated the findings of improved hindlimb perfusion and muscle function. Furthermore, EPC-CM transplantation stimulated the mobilization of bone marrow (BM)-derived EPC compared to control (678.7±44.1 vs. 340.0±29.1 CD34⁺/CD45⁻ cells/1×10⁵ mononuclear cells, P<0.05) and their recruitment to the ischemic muscles (5.9±0.7 vs. 2.6±0.4 CD34⁺ cells/HPF, P<0.001) 3 days after the last injection.

Conclusions/Significance

Intramuscular injection of EPC-CM is as effective as cell transplantation for promoting tissue revascularization and functional recovery. Owing to the technical and practical limitations of cell therapy, cell free conditioned media may represent a potent alternative for therapeutic angiogenesis in ischemic cardiovascular diseases.     

Short-Term Curative Effect of Endovascular Stent-Graft Treatment for Aortic Diseases in China: A Systematic Review

Introduction

We analyzed the short-term efficacy of endovascular treatment for aortic diseases by summarizing all available published data on endovascular stent-graft treatment for abdominal aortic aneurysm (AAA), thoracic aortic aneurysm (TAA), type A aortic dissection (type A AD) and type B aortic dissection (type B AD) in China.

Methods

We performed a systematic analysis of 935 published series on retrograde endovascular treatment for aortic diseases in China from January 1996 to November 2010. Based on the inclusion criteria, 159 studies, involving a total of 5531 patients, were included.

Results

There were no significant differences in procedural success among the studies (P>0.05). The rates of overall neurologic complications and stroke were significantly different in all two-group comparisons (P<0.01). The type A AD patients had the highest rates of neurologic complications (both 6.67±0.00%), and the AAA patients had the lowest rates (0.31±0.04% and 0.11±0.02%). Significant differences were noted in the rates of cardiac, renal, pulmonary and visceral complications, which were all higher in the type A AD patients than in the other three groups (P<0.01). The endoleak rate was highest in the TAA patients (19.27±5.74%) and was similar in the type A AD patients (P>0.05). A significant difference was noted between the 30-day mortality rate of the type A AD patients and the AAA or type B AD patients (P<0.05).

Conclusion

Endovascular stent-graft is a feasible and safe treatment for aortic diseases, with high procedural success and low incidences of post-procedural complications and short-term mortality. Endovascular treatment for AAA and type B AD is more efficient than for type A AD and TAA.     

Catheter-Based Renal Sympathetic Denervation Significantly Inhibits Atrial Fibrillation Induced by Electrical Stimulation of the Left Stellate Ganglion and Rapid Atrial Pacing

Background

Sympathetic activity involves the pathogenesis of atrial fibrillation (AF). Renal sympathetic denervation (RSD) decreases sympathetic renal afferent nerve activity, leading to decreased central sympathetic drive. The aim of this study was to identify the effects of RSD on AF inducibility induced by hyper-sympathetic activity in a canine model.

Methods

To establish a hyper-sympathetic tone canine model of AF, sixteen dogs were subjected to stimulation of left stellate ganglion (LSG) and rapid atrial pacing (RAP) for 3 hours. Then animals in the RSD group (n = 8) underwent radiofrequency ablation of the renal sympathetic nerve. The control group (n = 8) underwent the same procedure except for ablation. AF inducibility, effective refractory period (ERP), ERP dispersion, heart rate variability and plasma norepinephrine levels were measured at baseline, after stimulation and after ablation.

Results

LSG stimulation combined RAP significantly induced higher AF induction rate, shorter ERP, larger ERP dispersion at all sites examined and higher plasma norepinephrine levels (P<0.05 in all values), compared to baseline. The increased AF induction rate, shortened ERP, increased ERP dispersion and elevated plasma norepinephrine levels can be almost reversed by RSD, compared to the control group (P<0.05). LSG stimulation combined RAP markedly shortened RR-interval and standard deviation of all RR-intervals (SDNN), Low-frequency (LF), high-frequency (HF) and LF/HF ratio (P<0.05). These changes can be reversed by RSD, compared to the control group (P<0.05).

Conclusions

RSD significantly reduced AF inducibility and reversed the atrial electrophysiological changes induced by hyper-sympathetic activity.     

Niacin Reduces Atherosclerosis Development in APOE*3Leiden.CETP Mice Mainly by Reducing NonHDL-Cholesterol

Objective

Niacin potently lowers triglycerides, mildly decreases LDL-cholesterol, and largely increases HDL-cholesterol. Despite evidence for an atheroprotective effect of niacin from previous small clinical studies, the large outcome trials, AIM-HIGH and HPS2-THRIVE did not reveal additional beneficial effects of niacin (alone or in combination with laropiprant) on top of statin treatment. We aimed to address this apparent discrepancy by investigating the effects of niacin without and with simvastatin on atherosclerosis development and determine the underlying mechanisms, in APOE*3Leiden.CETP mice, a model for familial dysbetalipoproteinemia (FD).

Approach and Results

Mice were fed a western-type diet containing cholesterol without or with niacin (120 mg/kg/day), simvastatin (36 mg/kg/day) or their combination for 18 weeks. Similarly as in FD patients, niacin reduced total cholesterol by -39% and triglycerides by −50%, (both P<0.001). Simvastatin and the combination reduced total cholesterol (−30%; −55%, P<0.001) where the combination revealed a greater reduction compared to simvastatin (−36%, P<0.001). Niacin decreased total cholesterol and triglycerides primarily by increasing VLDL clearance. Niacin increased HDL-cholesterol (+28%, P<0.01) and mildly increased reverse cholesterol transport. All treatments reduced monocyte adhesion to the endothelium (−46%; −47%, P<0.01; −53%, P<0.001), atherosclerotic lesion area (−78%; −49%, P<0.01; −87%, P<0.001) and severity. Compared to simvastatin, the combination increased plaque stability index [(SMC+collagen)/macrophages] (3-fold, P<0.01). Niacin and the combination reduced T cells in the aortic root (−71%, P<0.01; −81%, P<0.001). Lesion area was strongly predicted by nonHDL-cholesterol (R² = 0.69, P<0.001) and to a much lesser extent by HDL-cholesterol (R² = 0.20, P<0.001).

Conclusion

Niacin decreases atherosclerosis development mainly by reducing nonHDL-cholesterol with modest HDL-cholesterol-raising and additional anti-inflammatory effects. The additive effect of niacin on top of simvastatin is mostly dependent on its nonHDL-cholesterol-lowering capacities. These data suggest that clinical beneficial effects of niacin are largely dependent on its ability to lower LDL-cholesterol on top of concomitant lipid-lowering therapy.     

Bone Marrow Alterations and Lower Endothelial Progenitor Cell Numbers in Critical Limb Ischemia Patients

Background

Critical limb ischemia (CLI) is characterized by lower extremity artery obstruction and a largely unexplained impaired ischemic neovascularization response. Bone marrow (BM) derived endothelial progenitor cells (EPC) contribute to neovascularization. We hypothesize that reduced levels and function of circulating progenitor cells and alterations in the BM contribute to impaired neovascularization in CLI.

Methods

Levels of primitive (CD34⁺ and CD133⁺) progenitors and CD34⁺KDR⁺ EPC were analyzed using flow cytometry in blood and BM from 101 CLI patients in the JUVENTAS-trial ({"type":"clinical-trial","attrs":{"text":"NCT00371371","term_id":"NCT00371371"}}NCT00371371) and healthy controls. Blood levels of markers for endothelial injury (sE-selectin, sICAM-1, sVCAM-1, and thrombomodulin), and progenitor cell mobilizing and inflammatory factors were assessed by conventional and multiplex ELISA. BM levels and activity of the EPC mobilizing protease MMP-9 were assessed by ELISA and zymography. Circulating angiogenic cells (CAC) were cultured and their paracrine function was assessed.

Results

Endothelial injury markers were higher in CLI (P<0.01). CLI patients had higher levels of VEGF, SDF-1α, SCF, G-CSF (P<0.05) and of IL-6, IL-8 and IP-10 (P<0.05). Circulating EPC and BM CD34⁺ cells (P<0.05), lymphocytic expression of CXCR4 and CD26 in BM (P<0.05), and BM levels and activity of MMP-9 (P<0.01) were lower in CLI. Multivariate regression analysis showed an inverse association between IL-6 and BM CD34⁺ cell levels (P = 0.007). CAC from CLI patients had reduced paracrine function (P<0.0001).

Conclusion

CLI patients have reduced levels of circulating EPC, despite profound endothelial injury and an EPC mobilizing response. Moreover, CLI patients have lower BM CD34⁺-cell levels, which were inversely associated with the inflammatory marker IL-6, and lower BM MMP-9 levels and activity. The results of this study suggest that inflammation-induced BM exhaustion and a disturbed progenitor cell mobilization response due to reduced levels and activity of MMP-9 in the BM and alterations in the SDF-1α/CXCR4 interaction contribute to the attenuated neovascularization in CLI patients.     

Stomach Virtual Non-Enhanced CT with Second-Generation,Dual-Energy CT: A Preliminary Study

Objectives

To compare the true non-enhanced (TNE) and virtual non-enhanced (VNE) data sets in patients who underwent gastric preoperative dual-energy CT (DECT) and to evaluate potential radiation dose reduction by omitting a TNE scan.

Methods

A total of 74 patients underwent gastric DECT. The mean CT values, length, image quality and effective radiation doses for VNE and TNE images were compared.

Results

There was no statistical difference in maximal thickness of gastric tumors and maximal diameter of enlarged lymph nodes among the TNE and VNE images (P>0.05). The mean CT value differences between TNE and VNE were statistically significant for all tissue types, except for aorta attenuation measurements (P<0.05), but the absolute differences were under 10 HU. Lower noise was found for VNE images than TNE images (P<0.01). Image quality of VNE was diagnostic but lower than that of TNE (P<0.01). The dose reduction achieved by omitting the TNE acquisition was 21.40±4.44%.

Conclusion

VNE scan may potentially replace TNE as part of a multi-phase gastric preoperative staging imaging protocol with consequent saving in radiation dose.     

Determinants of Fatigue after First-Ever Ischemic Stroke during Acute Phase

Background and Purpose

Fatigue after stroke is common and has a negative impact on rehabilitation and survival. However, its pathogenesis and contributing factors remain unclear. The purpose of this study was to identify factors influencing the occurrence of fatigue after first-ever ischemic stroke in acute phase.

Methods

We examined 265 consecutive patients with first-ever ischemic stroke during acute phase (within 2 weeks) in two tertiary stroke care hospitals in Henan, China. We documented patients’ demographic and clinical characteristics through face-to-face interviews using structured questionnaires and reviews of medical records. Post-stroke fatigue was defined as a score of ≥4 using the Fatigue Severity Scale. Multivariate logistic regression was used to examine post-stroke fatigue in relation to socio-demographic, lifestyle, clinical characteristics and family function.

Results

About 40% first-ever ischemic stroke patients experienced post-stroke fatigue in acute phase. Post-stroke fatigue was associated with lack of exercise before stroke (adjusted odds ratio 4.01, 95% CI 1.95–8.24), family dysfunction (2.63, 1.20–5.80), depression (2.39, 1.02–5.58), the presence of pre-stroke fatigue (4.89, 2.13–11.21), use of sedative medications (4.14, 1.58–10.88), coronary heart disease (3.38, 1.46–7.79) and more severe Modified Rankin Scale (2.55, 1.65–3.95).

Conclusions

The causes of post-stroke fatigue are multifaceted. More physical exercise, improving family function, reducing depression and appropriate use of sedative medications may be helpful in preventing post-stroke fatigue.     

Copeptin,Procalcitonin and Routine Inflammatory Markers–Predictors of Infection after Stroke

Background

Early predictors for the development of stroke-associated infection may identify patients at high risk and reduce post-stroke infection and mortality.

Methods

In 383 prospectively enrolled acute stroke patients we assessed time point and type of post-stroke infections (i.e. pneumonia, urinary tract infection (UTI) other infection (OI)). Blood samples were collected on admission, and days 1, and 3 to assess white blood cells (WBC), monocytes, C-reactive protein (CRP), procalcitonin (PCT), and copeptin. To determine the magnitude of association with the development of infections, odds ratios (OR) were calculated for each prognostic blood marker. The discriminatory ability of different predictors was assessed, by calculating area under the receiver operating characteristic curves (AUC). Prognostic models including the three parameters with the best performance were identified.

Results

Of 383 patients, 66 (17.2%) developed an infection after onset of stroke. WBC, CRP, copeptin and PCT were all independent predictors of any infection, pneumonia and UTI developed at least 24 hours after measurements. The combination of the biomarkers WBC, CRP and copeptin (AUC: 0.92) and WBC, CRP and PCT (AUC: 0.90) showed a better predictive accuracy concerning the development of pneumonia during hospitalization compared to each marker by itself (p-Wald <0.0001).

Conclusion

Among ischemic stroke patients, copeptin, PCT, WBC and CRP measured on admission were predictors of infection in general, and specifically for pneumonia and UTI within 5 days after stroke. The combination of these biomarkers improved the prediction of patients who developed an infection.     

Visceral Adiposity Index May Be a Surrogate Marker for the Assessment of the Effects of Obesity on Arterial Stiffness

Objective

The relationship between obesity and cardiovascular disease (CVD) remains unclear. This study aims to describe the relationship between arterial stiffness and obesity in order to investigate the effects of obesity on CVD.

Methods

We collected data from 5,158 individuals over 40 years of age from a cross-sectional study in Nanjing, China. Anthropometric, demographic, hemodynamic measurements and arterial stiffness measured through brachial-ankle pulse wave velocity (baPWV) were obtained. Subjects were grouped by body mass index (BMI), waist circumference (WC) and visceral adiposity index (VAI), a sex-specific index based on BMI, WC, triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C).

Results

The multivariate regression analysis revealed a negative but weak effect of BMI (β = −0.047, P<0.001) on baPWV, but failed to demonstrate any significant effect of WC on baPWV while VAI was a positive independent indicator of baPWV (β = 0.023, P = 0.022). The unadjusted baPWV significantly increased across groups with higher obesity categories (P<0.01). Although the positive association was lost after adjustments for confounding factors in the BMI or WC categories (P>0.05), it was still obtained between baPWV and VAI quartile (P<0.01). No differences were observed among the metabolically healthy groups or the metabolically abnormal groups in the BMI and WC categories (P>0.05). However, baPWV significantly increased across groups with higher VAI categories even in the same metabolic category (P<0.01).

Conclusions

This study supports the concept of heterogeneity of metabolic status among individuals within the same obesity range. Obese individuals are at an increased risk of arterial stiffness regardless of their metabolic conditions. VAI may be a surrogate marker for the assessment of obesity and the effects of obesity on arterial stiffness.