Abstract Objectives This study sought to determine whether splenic activation after acute coronary syndrome (ACS) is linked to leukocyte proinflammatory remodeling and whether splenic activity ...independently predicts the risk of cardiovascular disease (CVD) events. Background Pre-clinical data suggest the existence of a cardiosplenic axis, wherein activation of hematopoietic tissues (notably in the spleen) results in liberation of proinflammatory leukocytes and accelerated atherosclerotic inflammation. However, it is presently unknown whether a cardiosplenic axis exists in humans and whether splenic activation relates to CVD risk. Methods18 F-fluorodeoxyglucose (18 FDG)–positron emission tomography (PET) imaging was performed in 508 individuals across 2 studies. In the first study, we performed FDG-PET imaging in 22 patients with recent ACS and 22 control subjects. FDG uptake was measured in spleen and arterial wall, whereas proinflammatory gene expression of circulating leukocytes was assessed by quantitative real-time polymerase chain reaction. In a second study, we examined the relationship between splenic tissue FDG uptake with subsequent CVD events during follow-up (median 4 years) in 464 patients who previously had undergone FDG-PET imaging. Results Splenic activity increased after ACS and was significantly associated with multiple indices of inflammation: 1) up-regulated gene expression of proinflammatory leukocytes; 2) increased C-reactive protein; and 3) increased arterial wall inflammation (FDG uptake). Moreover, in the second study, splenic activity (greater than or equal to the median) was associated with an increased risk of CVD events (hazard ratio HR: 3.3; 95% confidence interval CI: 1.5 to 7.3; p = 0.003), which remained significant after adjustment for CVD risk factors (HR: 2.26; 95% CI: 1.01 to 5.06; p = 0.04) and for arterial FDG uptake (HR: 2.68; 95% CI: 1.5 to 7.4; p = 0.02). Conclusions Our findings demonstrate increased splenic metabolic activity after ACS and its association with proinflammatory remodeling of circulating leukocytes. Moreover, we observed that metabolic activity of the spleen independently predicted risk of subsequent CVD events. Collectively, these findings provide evidence of a cardiosplenic axis in humans similar to that shown in pre-clinical studies.
Abstract Objectives This study sought to determine prognostic value of nonobstructive coronary artery disease (CAD) for atherosclerotic cardiovascular disease (ASCVD) events and to determine whether ...incorporation of this information into the pooled cohort equation reclassifies recommendations for statin therapy as defined by the 2013 guidelines for cholesterol management of the American College of Cardiology and American Heart Association (ACC/AHA). Background Detection of nonobstructive CAD by coronary computed tomography angiography may improve risk stratification and permit individualized and more appropriate allocation of statin therapy. Methods This study determined the pooled hazard ratio of nonobstructive CAD for ASCVD events from published studies and incorporated this information into the ACC/AHA pooled cohort equation. The study calculated revised sex- and ethnicity-based 10-year ASCVD risk and determined boundaries corresponding to the original 7.5% risk for ASCVD events. It also assessed reclassification for statin eligibility by incorporating the results from meta-analysis to individual patients from a separate cohort. Results This study included 2 studies (2,295 subjects; 66% male; prevalence of nonobstructive CAD, 47%; median follow-up, 49 months; 67 ASCVD events). The hazard ratio of nonobstructive CAD for ASCVD events was 3.2 (95% confidence interval: 1.5 to 6.7). Incorporation of this information into the pooled cohort equation resulted in reclassification toward statin eligibility in individuals with nonobstructive CAD, with an original ASCVD score of 3.0% and 5.9% or higher in African-American women and men and a score of 4.4% and 4.6% or higher in Caucasian women and men, respectively. The absence of nonobstructive CAD resulted in reclassification toward statin ineligibility if the original ASCVD score was as 10.0% and 17.9% or lower in African-American women and men and 13.7% and 14.3% or lower in Caucasian women and men, respectively. Reclassification is observed in 14% of patients. Conclusions Detection of nonobstructive CAD by coronary computed tomography angiography improves risk stratification and permits individualized and more appropriate allocation of statin therapy across sex and ethnicity groups.
Abstract Objective Renal colic (RC) is a common clinical presentation in the emergency department (ED). Prompt and effective pain control is one of the first responsibilities of emergency physicians. ...The aim of this study was to evaluate the analgesic effect of adding lidocaine to morphine compared to morphine alone in patients presenting to the ED with RC. Methods In a double-blind, randomized controlled trial, a total of 110 adult patients of both sexes, aged 18 to 50 years, who presented to the ED with signs and symptoms suggestive of RC were randomly assigned into 1 of 2 groups. Patients in group A received morphine (0.1 mg/kg) plus lidocaine (1.5 mg/kg), whereas those in group B received morphine (0.1 mg/kg) plus normal saline 0.9% as placebo. All patients were asked to rate the intensity of their pain and nausea on a 0- to 10-point visual analog scale before and at 5, 10, 30, 60, and 120 minutes after intervention. Results There was a statistically significant time trend decline in both groups for both pain and nausea scores ( P < .01). Repeated-measures analysis showed a significant effect for the interaction between group and time of persistent pain ( P = .034), but there was no significant group effect in this regard ( P = .146). Median times to being pain free in the group receiving morphine plus lidocaine and in the group taking morphine alone were 87.02 minutes (95% confidence interval CI, 74.23-94.82) and 100.12 minutes (95% CI, 89.95-110.23), respectively ( P = .071). Repeated-measures analysis also showed a significant group effect for nausea ( P = .038), but there was no interaction between group and time in this regard ( P = .243). The median nausea-free times in the group receiving morphine plus lidocaine and the group receiving morphine alone were 26.6 minutes (95% CI, 14.16-39.03) and 58.33 minutes (95% CI, 41.85-74.82), respectively. This time difference was statistically significant ( P < .001). Conclusions Using lidocaine may be recommended as an effective, safe, and inexpensive adjuvant to morphine in improving nausea and reducing the time needed to achieve pain and nausea relief in patients visiting the ED with acute RC.
Objectives The purpose of this study was to test whether high-dose statin treatment would result in a reduction in periodontal inflammation as assessed by18 F-fluorodeoxyglucose positron emission ...tomography (FDG-PET)/computed tomography (CT). Background Periodontal disease (PD) is an independent risk factor for atherosclerosis. Methods Eighty-three adults with risk factors or with established atherosclerosis and who were not taking high-dose statins were randomized to atorvastatin 80 mg vs. 10 mg in a multicenter, double-blind trial to evaluate the impact of atorvastatin on arterial inflammation. Subjects were evaluated using FDG-PET/CT at baseline and at 4 and 12 weeks. Arterial and periodontal tracer activity was assessed while blinded to treatment allocation, clinical characteristics, and temporal sequence. Periodontal bone loss (an index of PD severity) was evaluated using contrast-enhanced CT images while blinded to clinical and imaging data. Results Seventy-one subjects completed the study, and 59 provided periodontal images for analysis. At baseline, areas of severe PD had higher target-to-background ratio (TBR) compared with areas without severe PD (mean TBR: 3.83 95% confidence interval (CI): 3.36 to 4.30 vs. 3.18 95% CI: 2.91 to 3.44, p = 0.004). After 12 weeks, there was a significant reduction in periodontal inflammation in patients randomized to atorvastatin 80 mg vs. 10 mg (ΔTBR 80 mg vs. 10 mg group: mean −0.43 95% CI: −0.83 to −0.02, p = 0.04). Between-group differences were greater in patients with higher periodontal inflammation at baseline (mean −0.74 95% CI: −1.29 to −0.19, p = 0.01) and in patients with severe bone loss at baseline (−0.61 95% CI: −1.16 to −0.054, p = 0.03). Furthermore, the changes in periodontal inflammation correlated with changes in carotid inflammation (R = 0.61, p < 0.001). Conclusions High-dose atorvastatin reduces periodontal inflammation, suggesting a newly recognized effect of statins. Given the concomitant changes observed in periodontal and arterial inflammation, these data raise the possibility that a portion of that beneficial impact of statins on atherosclerosis relate to reductions in extra-arterial inflammation, for example, periodontitis. (Evaluate the Utility of 18FDG-PET as a Tool to Quantify Atherosclerotic Plaque; NCT00703261 )
Abstract Background Proper timing of catheter insertion and the use of a suitable surgical method are essential parts of producing rat models to evaluate neuropathic bladder following spinal cord ...injury (SCI). Methods Thirty-two female Sprague-Dawley rats were randomly allocated into four groups. Group 1 underwent surgical laminectomy using the classic method. Group 2 underwent SCI 7 d following insertion of the catheter, and group 3 underwent sham operation. For bladder catheterization, a 4.5 Fr catheter was fixed into the bladder and tunneled beneath the skin to reach out at the nape of the neck. Group 4 underwent urodynamic study via bladder catheter prior to surgery and every 10 d following the operation to determine the exact time of establishing neuropathic bladder following spinal shock. The animals' survival rate and bladder wall's histopathologic changes were assessed 30 d following the operation. Results Simultaneous suprapubic catheter placement raised the mortality rate in group 1 in comparison with group 2. Repeated urodynamic study in group 4 showed hypertonic behavior in the bladder 10 d after SCI, with significantly increased leak point pressure and bladder capacity; however, the end filling pressure and constant neuropathic bladder on cystometric indices are attained from 20 d after the operation. Conclusions Insertion of a bladder catheter 1 wk prior to SCI provides an applicable route for repeated cystometric studies in rats. The results demonstrate that sustained bladder overactivity is established in rats 20 d after SCI and animals are ready for further experiments on neuropathic bladder dysfunction following this period.
Abstract Background Patients with familial hypercholesterolemia (FH) are characterized by elevated atherogenic lipoprotein particles, predominantly low-density lipoprotein cholesterol (LDL-C), which ...is associated with accelerated atherogenesis and increased cardiovascular risk. Objectives This study used18 F-fluorodeoxyglucose positron emission tomography (18 FDG-PET) to investigate whether arterial inflammation is higher in patients with FH and, moreover, whether lipoprotein apheresis attenuates arterial wall inflammation in FH patients. Methods In total, 38 subjects were recruited: 24 FH patients and 14 normolipidemic controls. All subjects underwent FDG-PET imaging at baseline. Twelve FH patients who met the criteria for lipoprotein apheresis underwent apheresis procedures followed by a second FDG-PET imaging 3 days (range 1 to 4 days) after apheresis. Subsequently, the target-to-background ratio (TBR) of FDG uptake within the arterial wall was assessed. Results In FH patients, the mean arterial TBR was higher compared with healthy controls (2.12 ± 0.27 vs. 1.92 ± 0.19; p = 0.03). A significant correlation was observed between baseline arterial TBR and LDL-C (R = 0.37; p = 0.03) that remained significant after adjusting for statin use (β = 0.001; p = 0.02) and atherosclerosis risk factors (β = 0.001; p = 0.03). LDL-C levels were significantly reduced after lipoprotein apheresis (284 ± 118 mg/dl vs. 127 ± 50 mg/dl; p < 0.001). There was a significant reduction of arterial inflammation after lipoprotein apheresis (TBR: 2.05 ± 0.31 vs. 1.91 ± 0.33; p < 0.02). Conclusions The arterial wall of FH patients is characterized by increased inflammation, which is markedly reduced after lipoprotein apheresis. This lends support to a causal role of apoprotein B–containing lipoproteins in arterial wall inflammation and supports the concept that lipoprotein-lowering therapies may impart anti-inflammatory effects by reducing atherogenic lipoproteins.
Objective Fluoxetine is one of the most common medications used for the treatment of depression. Recent studies have demonstrated the possible effect of this drug on bone. The purpose of this study ...was to evaluate the effect of flouxetine on bone in Sprague-Dawley rats randomly divided into 3 groups (n = 7). Study design Two calvarial defects, 5 mm diameter, were prepared in parietal bone. The left defects were filled with natural bovine bone mineral (NBBM) and the right defects were left untreated. The first group did not receive fluoxetine. The second group and the third group received 7.5 mg and 15 mg flouxetine, respectively, daily by gastric gavage. The animals were killed 8 weeks after surgery, and the amount of bone regeneration was evaluated using histometric analysis. Results The defects showed dose-dependent increase in bone formation. The bone fill length had statistical significant differences between NBBM/flouxetine (15 mg) group and other groups ( P < .05). The presence of the NBBM had positive effect on the bone formation in all groups in so far as the maximum amount of the increasing effect was seen in those rats filled with NBBM that received 15 mg flouxetine ( P < .05). The minimum bone length in fluoxetine-treated defects was seen in 7.5 mg defects (0.36 mm) Conclusion Fluoxetine may improve the amount of bone regeneration in the rat calvarial defects.
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