Clinical Presentations,Antiplatelet Strategies and Prognosis of Patients with Stent Thrombosis: An Observational Study of 140 Patients

Background

Until now there has been scarce evidence regarding an optimal antiplatelet strategy and clinical outcomes for patients who had suffered from stent thrombosis (ST).

Methods and Results

140 patients who suffered from stent thrombosis were prospectively registered. Patients received dual (aspirin and 150 mg clopidogrel, N = 66) or triple (additional cilostazol, N = 74) antiplatelet therapy at the physician’s discretion. Thereafter platelet reactivity and one year clinical outcomes were analyzed. The primary outcome included the composite of cardiac death, non-fatal myocardial infarction (MI) or stroke at one year,which developed in 41 (29.3%) patients, consisting of 31 (22.1%) cardiac death, 9 (6.4%) non-fatal MI and 1 (1.4%) stroke. Recurrent definite and probable ST according to ARC definition was observed in 8 (5.7%) and 14 (10.0%) patients, respectively. Triple therapy was associated with significantly lower platelet reactivities (50.2±17.8, % vs. 59.6±17.2, %, P = 0.002) compared to high dose dual antiplatelet therapy. However, the incidence of primary events (24.3% vs. 34.8%, P = 0.172) did not differ between triple and dual antiplatelet therapies. High on-treatment platelet reactivity (HR: 8.35, 95% CI: 2.234∼30.867, P = 0.002) and diabetes (HR: 3.732, 95% CI: 1.353∼10.298, P = 0.011) were independent predictors of primary events.

Conclusions

Patients who suffered from stent thrombosis have a poor prognosis even after revascularization with intensive antiplatelet therapy. Triple antiplatelet therapy was more effective in reducing on-treatment platelet reactivity, compared to high dose dual antiplatelet therapy.     

A Randomized,Single-Ascending-Dose,Ivermectin-Controlled,Double-Blind Study of Moxidectin in Onchocerca volvulus Infection

Background

Control of onchocerciasis as a public health problem in Africa relies on annual mass ivermectin distribution. New tools are needed to achieve elimination of infection. This study determined in a small number of Onchocerca volvulus infected individuals whether moxidectin, a veterinary anthelminthic, is safe enough to administer it in a future large study to further characterize moxidectin''s safety and efficacy. Effects on the parasite were also assessed.

Methodology/Principal Findings

Men and women from a forest area in South-eastern Ghana without ivermectin mass distribution received a single oral dose of 2 mg (N = 44), 4 mg (N = 45) or 8 mg (N = 38) moxidectin or 150 µg/kg ivermectin (N = 45) with 18 months follow up. All ivermectin and 97%–100% of moxidectin treated participants had Mazzotti reactions. Statistically significantly higher percentages of participants treated with 8 mg moxidectin than participants treated with ivermectin experienced pruritus (87% vs. 56%), rash (63% vs. 42%), increased pulse rate (61% vs. 36%) and decreased mean arterial pressure upon 2 minutes standing still after ≥5 minutes supine relative to pre-treatment (61% vs. 27%). These reactions resolved without treatment. In the 8 mg moxidectin and ivermectin arms, the mean±SD number of microfilariae/mg skin were 22.9±21.1 and 21.2±16.4 pre-treatment and 0.0±0.0 and 1.1±4.2 at nadir reached 1 and 3 months after treatment, respectively. At 6 months, values were 0.0±0.0 and 1.6±4.5, at 12 months 0.4±0.9 and 3.4±4.4 and at 18 months 1.8±3.3 and 4.0±4.8, respectively, in the 8 mg moxidectin and ivermectin arm. The reduction from pre-treatment values was significantly higher after 8 mg moxidectin than after ivermectin treatment throughout follow up (p<0.01).

Conclusions/Significance

The 8 mg dose of moxidectin was safe enough to initiate the large study. Provided its results confirm those from this study, availability of moxidectin to control programmes could help them achieve onchocerciasis elimination objectives.

Trial Registration

ClinicalTrails.gov NCT00300768     

Is Bladder Tumor Location Associated with Prostate Cancer Detection after Intravesical Bacillus Calmette-Guérin Instillation?

Objectives

The aim of this study was to evaluate the effect of bladder tumor (BT) location on prostate cancer (PCa) detection in patients with elevated PSA levels after intravesical BCG instillation.

Methods

Between February 2004 and January 2013 prostate biopsies were performed in 59 non-muscle invasive bladder cancer (NMIBC) patients whose PSA level were elevated (≥3 ng/ml) after a 6 week course of intravesical BCG (Oncotice, 12.5 mg in 50 ml normal saline). Differences in PCa detection according to the BT location [bladder neck and/or trigone (Group 1, n = 22) vs. other locations (Group 2, n = 37)] were evaluated. The Fisher''s exact test and the Mann-Whitney U test were used to evaluate the association between categorical and continuous variables, respectively.

Results

A total of 14 patients (23.7%) were diagnosed with PCa. The mean ± standard deviation (SD) PSA before intravesical BCG instillation and prostate biopsy were 1.36±1.04 ng/ml in Group 1 and 1.09±1.12 ng/ml in Group 2 (P = 0.633), and 6.05±3.57 ng/ml in Group 1 and 5.13±3.88 ng/ml in Group 2 (P = 0.378), respectively. Interestingly, whereas PCa was detected upon biopsy in only one patient in Group 1 (4.5%), 13 cases were detected in Group 2 (35.1%) (P = 0.009).

Conclusions

PCa detection after intravesical BCG was highly associated with BT location. Prostate biopsy should therefore be considered when PSA level is elevated after BCG instillation and his BT is located far from the bladder neck.     

The Impact of Sexual Abuse in Patients Undergoing Colonoscopy

Background

Sexual abuse has been linked to strong effects on gastrointestinal health. Colonoscopy can provoke intense emotional reactions in patients with a sexual abuse history and may lead to avoidance of endoscopic procedures.

Objective

To determine whether care around colonoscopy needs adjustment for patients with sexual abuse experience, thereby exploring targets for the improvement of care around colonoscopic procedures.

Methods

Questionnaires were mailed to patients (n = 1419) from two centers within 11 months after colonoscopy. Differences in experience of the colonoscopy between patients with and without a sexual abuse history were assessed and patients'' views regarding physicians'' inquiry about sexual abuse and care around endoscopic procedures were obtained.

Results

A total of 768 questionnaires were analyzed. The prevalence of sexual abuse was 3.9% in male and 9.5% in female patients. Patients born in a non-western country reported more sexual abuse (14.9%) than those born in a western country (6.3%; p = 0.008). Discomfort during colonoscopy was indicated on a scale from 0 to 10, mean distress score of patients with sexual abuse was 4.8(±3.47) compared to 3.5(±3.11) in patients without a sexual abuse history (p = 0.007). Abdominal pain was a predictor for higher distress during colonoscopy (β = −0.019 (SE = 0.008); p = 0.02, as well as the number of complaints indicated as reason for colonoscopy (β = 0.738 (SE = 0.276); p = 0.008). Of patients with sexual abuse experience, 53.8% believed gastroenterologists should ask about it, 43.4% said deeper sedation during colonoscopy would diminish the distress.

Conclusions

Sexual abuse is prevalent in patients presenting for colonoscopy. Patients with a sexual abuse history experience more distress during the procedure and indicate that extra attention around and during colonoscopy may diminish this distress.     

Squamous Tissue Lymphocytes in the Esophagus of Controls and Patients with Reflux Esophagitis and Barrett’s Esophagus Are Characterized by a Non-Inflammatory Phenotype

Background and Objective

Reflux esophagitis (RE) is characterized by inflammation of the squamous epithelium (SQ) of the esophagus and may progress to Barrett’s esophagus (BE) characterized by intestinal metaplasia. The role of inflammation in this transition has been postulated but lacks experimental evidence. Here, the inflammatory responses in the esophagus of these patients were investigated.

Patients and Methods

Fifty-one esophageal biopsies from with patients BE (n = 19), RE (n = 8) and controls (n = 23) were analyzed. T-cells were analyzed before and after ex vivo expansion (14 days) by multicolor flow cytometric analysis. The following markers were studied: CD3, CD4, CD8 (T-cell markers), Granzyme B (marker of cytotoxicity), CD103 (αE/epithelial integrin) and NKg2a (inhibitory receptor on T-cells and NK-cells).

Results

Analysis of ex vivo cultures from normal looking SQ from controls, RE patients, and BE patients revealed no significant differences in the number and phenotypes of T-cells. In contrast, tissue from RE was different to normal SQ in four aspects: 1) higher percentages of CD3⁺CD4⁺-cells (72±7% vs 48±6%, p = 0.01) and 2) CD8⁺GranzymeB⁺ -cells (53±11% vs 26±4%, p<0.05), while 3) lower percentages of CD4⁺CD103⁺-cells (45±19% vs 80±3%, p = 0.02) and 4) CD8⁺NKg2a⁺- cells (31±12% vs 44±5%).

Conclusion

Despite the fact that both tissues are exposed to the same reflux associated inflammatory triggers, the immune response observed in RE is clearly distinct from that in SQ of BE. The differences in immune responses in BE tissue might contribute to its susceptibility for transformation into intestinal metaplasia.     

Decentralization of Care for Adults with Congenital Heart Disease in the United States: A Geographic Analysis of Outpatient Surgery

Background

Guidelines recommend that adults with congenital heart disease (CHD) undergo noncardiac surgery in regionalized centers of expertise, but no studies have assessed whether this occurs in the United States. We hypothesized that adults with CHD are less likely than children to receive care at specialized CHD centers.

Methods

Using a comprehensive state ambulatory surgical registry (California Ambulatory Surgery Database, 2005–2011), we calculated the proportion of adult and pediatric patients with CHD who had surgery at a CHD center, distance to the nearest CHD center, and distance to the facility where surgery was performed.

Results

Patients with CHD accounted for a larger proportion of the pediatric population (n = 11,254, 1.0%) than the adult population (n = 10,547, 0.07%). Only 2,741 (26.0%) adults with CHD had surgery in a CHD center compared to 6,403 (56.9%) children (p<0.0001). Adult CHD patients who had surgery at a non-specialty center (11.9±15.4 miles away) lived farther from the nearest CHD center (37.9±43.0 miles) than adult CHD patients who had surgery at a CHD center (23.2±28.4 miles; p<0.0001). Pediatric CHD patients who had surgery at a non-specialty center (18.0±20.7 miles away) lived farther from the nearest CHD center (35.7±45.2 miles) than pediatric CHD patients who had surgery at a CHD center (22.4±26.0 miles; p<0.0001).

Conclusions

Unlike children with CHD, most adults with CHD (74%) do not have outpatient surgery at a CHD center. For both adults and children with CHD, greater distance from a CHD center is associated with having surgery at a non-specialty center. These results have significant public health implications in that they suggest a failing to achieve adequate regional access to specialized ACHD care. Further studies will be required to evaluate potential strategies to more reliably direct this vulnerable population to centers of expertise.     

Periaortic Brown Adipose Tissue as a Major Determinant of [18F]-Fluorodeoxyglucose Vascular Uptake in Atherosclerosis-Prone,ApoE?/? Mice

Background

[¹⁸F]-fluorodeoxyglucose (FDG) has been suggested for the clinical and experimental imaging of inflammatory atherosclerotic lesions. Significant FDG uptake in brown adipose tissue (BAT) has been observed both in humans and mice. The objective of the present study was to investigate the influence of periaortic BAT on apolipoprotein E-deficient (apoE^−/−) mouse atherosclerotic lesion imaging with FDG.

Methods

ApoE^−/− mice (36±2 weeks-old) were injected with FDG (12±2 MBq). Control animals (Group A, n = 7) were injected conscious and kept awake at room temperature (24°C) throughout the accumulation period. In order to minimize tracer activity in periaortic BAT, Group B (n = 7) and C (n = 6) animals were injected under anaesthesia at 37°C and Group C animals were additionally pre-treated with propranolol. PET/CT acquisitions were performed prior to animal euthanasia and ex vivo analysis of FDG biodistribution.

Results

Autoradiographic imaging indicated higher FDG uptake in atherosclerotic lesions than in the normal aortic wall (all groups, P<0.05) and the blood (all groups, P<0.01) which correlated with macrophage infiltration (R = 0.47; P<0.001). However, periaortic BAT uptake was either significantly higher (Group A, P<0.05) or similar (Group B and C, P = NS) to that observed in atherosclerotic lesions and was shown to correlate with in vivo quantified aortic FDG activity.

Conclusion

Periaortic BAT FDG uptake was identified as a confounding factor while using FDG for the non-invasive imaging of mouse atherosclerotic lesions.     

Associations between Family-Related Factors,Breakfast Consumption and BMI among 10- to 12-Year-Old European Children: The Cross-Sectional ENERGY-Study

Objective

To investigate associations of family-related factors with children’s breakfast consumption and BMI-z-score and to examine whether children’s breakfast consumption mediates associations between family-related factors and children’s BMI-z-score.

Subjects

Ten- to twelve-year-old children (n = 6374; mean age = 11.6±0.7 years, 53.2% girls, mean BMI-z-score = 0.4±1.2) and one of their parents (n = 6374; mean age = 41.4±5.3 years, 82.7% female, mean BMI = 24.5±4.2 kg/m²) were recruited from schools in eight European countries (Belgium, Greece, Hungary, the Netherlands, Norway, Slovenia, Spain, and Switzerland). The children self-reported their breakfast frequency per week. The body weight and height of the children were objectively measured. The parents responded to items on family factors related to breakfast (automaticity, availability, encouragement, paying attention, permissiveness, negotiating, communicating health beliefs, parental self-efficacy to address children’s nagging, praising, and family breakfast frequency). Mediation analyses were performed using multi-level regression analyses (child-school-country).

Results

Three of the eleven family-related variables were significantly associated with children’s BMI-z-score. The family breakfast frequency was negatively associated with the BMI-z-score; permissiveness concerning skipping breakfast and negotiating about breakfast were positively associated with the BMI-z-score. Children’s breakfast consumption was found to be a mediator of the two associations. All family-related variables except for negotiating, praising and communicating health beliefs, were significantly associated with children’s breakfast consumption.

Conclusions

Future breakfast promotion and obesity prevention interventions should focus on family-related factors including the physical home environment and parenting practices. Nevertheless, more longitudinal research and intervention studies to support these findings between family-related factors and both children’s breakfast consumption and BMI-z-score are needed.     

Red Blood Cell Distribution Width and Long-Term Outcome in Patients Undergoing Percutaneous Coronary Intervention in the Drug-Eluting Stenting Era: A Two-Year Cohort Study

Background

Previous studies suggest the higher the red blood cell distribution width (RDW) the greater the risk of mortality in patients with coronary artery disease (CAD). However, the relationship between RDW and long-term outcome in CAD patients undergoing percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) remains unclear. This study was designed to evaluate the long-term effect of RDW in patients treated with drug-eluting stent for CAD.

Methods

In total of 2169 non-anemic patients (1468 men, mean age 60.2±10.9 years) with CAD who had undergone successful PCI and had at least one drug-eluting stent were included in this study. Patients were grouped according to their baseline RDW: Quartile 1 (RDW<12.27%), Quartile 2 (12.27%≤RDW<13%), Quartile 3 (13%≤RDW<13.5%), and Quartile 4 (RDW≥13.5).

Results

The incidence of in-hospital mortality and death or myocardial infarction was significantly higher in Quartiles 3 and 4 compared with Quartile 1 (P<0.05). After a follow-up of 29 months, the incidence of all-cause death and stent thrombosis in Quartile 4 was higher than in Quartiles 1, 2, and 3 (P<0.05). The incidence of death/myocardial infarction/stroke and cardiac death in Quartile 4 was higher than in Quartiles 1 and 2 (P<0.05). Multivariate Cox regression analysis showed that RDW was an independent predictor of all-cause death (hazard ratio (HR) = 1.37, 95% confidence interval (CI) = 1.15–1.62, P<0.001) and outcomes of death/myocardial infarction/stroke (HR = 1.21, 95% CI = 1.04–1.39, P = 0.013). The cumulative survival rate of Quartile 4 was lower than that of Quartiles 1, 2, and 3 (P<0.05).

Conclusion

High RDW is an independent predictor of long-term adverse clinical outcomes in non-anemic patients with CAD treated with DES.     

Can Churches Play a Role in Combating the HIV/AIDS Epidemic? A Study of the Attitudes of Christian Religious Leaders in Madagascar

Introduction

Churches occupy an important social and cultural position in Madagascar. The sexual transmission of HIV raises controversies about the role that Churches can play in preventing HIV/AIDS. This cross-sectional survey investigated recommendations by religious leaders for condom use and other preventive strategies in the context of international guidelines.

Methods

A questionnaire was self-administered to a random sample of religious leaders. The questions related to preventive methods against HIV/AIDS such as: condom use, marital fidelity, sexual abstinence before marriage, and HIV-testing. Associations with recommendations for condom use were evaluated using univariate and multivariate logistic regression analyses.

Results

Of 231 religious leaders, 215 (93.1%) were willing to share their knowledge of HIV/AIDS with their congregations. The majority received their information from the media (N = 136, 58.9%), a minority from their church (N = 9, 3.9%), and 38 (16.4%) had received prior training on HIV. Nearly all (N = 212, 91.8%) knew that HIV could be sexually transmitted though only a few (N = 39, 16.9%) were aware of mother-to-child transmission or unsafe injections (N = 56, 24.2%). A total of 91 (39.4%) were willing to, or had recommended (N = 64, 27.7%), condom use, while 50 (21.6%) had undergone HIV testing. Only nine (3.9%) had ever cared for a person living with HIV/AIDS (PLHIV). Multivariable logistic regression shows that condom use recommendations by religious leaders were negatively associated with tertiary level education (OR: 0.3, 95% CI 0.1–0.7), and positively associated with knowing a person at risk (OR: 16.2, 95% CI 3.2–80.2), knowing of an ART center (OR: 2.6, 95% CI 1.4–4.8), and receiving information about HIV at school (OR: 2.6, 95% CI 1.2–5.6).

Conclusions

Malagasy church leaders could potentially become key players in HIV/AIDS prevention if they improved their knowledge of the illness, their commitment to international recommendations, and extended their interaction with people most at risk.     

Glucose-Induced Glucagon-Like Peptide 1 Secretion Is Deficient in Patients with Non-Alcoholic Fatty Liver Disease

Background & Aims

The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are gastrointestinal peptide hormones regulating postprandial insulin release from pancreatic β-cells. GLP-1 agonism is a treatment strategy in Type 2 diabetes and is evaluated in Non-alcoholic fatty liver disease (NAFLD). However, the role of incretins in its pathophysiology is insufficiently understood. Studies in mice suggest improvement of hepatic steatosis by GLP-1 agonism. We determined the secretion of incretins after oral glucose administration in non-diabetic NAFLD patients.

Methods

N = 52 patients (n = 16 NAFLD and n = 36 Non-alcoholic steatohepatitis (NASH) patients) and n = 50 matched healthy controls were included. Standardized oral glucose tolerance test was performed. Glucose, insulin, glucagon, GLP-1 and GIP plasma levels were measured sequentially for 120 minutes after glucose administration.

Results

Glucose induced GLP-1 secretion was significantly decreased in patients compared to controls (p<0.001). In contrast, GIP secretion was unchanged. There was no difference in GLP-1 and GIP secretion between NAFLD and NASH subgroups. All patients were insulin resistant, however HOMA2-IR was highest in the NASH subgroup. Fasting and glucose-induced insulin secretion was higher in NAFLD and NASH compared to controls, while the glucose lowering effect was diminished. Concomitantly, fasting glucagon secretion was significantly elevated in NAFLD and NASH.

Conclusions

Glucose-induced GLP-1 secretion is deficient in patients with NAFLD and NASH. GIP secretion is contrarily preserved. Insulin resistance, with hyperinsulinemia and hyperglucagonemia, is present in all patients, and is more severe in NASH compared to NAFLD. These pathophysiologic findings endorse the current evaluation of GLP-1 agonism for the treatment of NAFLD.     

24 Hour ST Segment Analysis in Transient Left Ventricular Apical Ballooning

Objective

The etiologic basis of transient left ventricular apical ballooning, a novel cardiac syndrome, is not clear. Among the proposed pathomechanisms is coronary vasospasm. Long-term ST segment analysis may detect vasospastic episodes but has not been reported.

Methods

30 consecutive patients with transient left ventricular apical ballooning, left ventricular dysfunction and normal or near-normal coronary arteries were investigated. A 24-hour Holter ECG was obtained after emergency admission. ST segment analysis was performed automatically in 2 leads and confirmed by visual inspection. Criteria for an ischemic event were: 1. ST elevation or 2. horizontal or down-sloping ST segments ≥1 min duration and ≥100 µV J+80 point deviation corrected for baseline ST-deviation.

Results

Patients presented with ST segment elevation (n = 19) and/or T wave inversion (n = 20) on admission ECG. Ejection fraction was 50±12%. No transient ST elevations were observed during Holter ECG analysis. In 3 patients, 8 transient episodes of ST depression were recorded. Durations of episodes varied between 75s and 790s (mean 229s). Maximal ST deviation averaged −191±71 µV. Ischemic burden was −1 to −22 mVs (mean −8 mVs). 27 patients showed no ischemic events.

Conclusions

ST segment analysis of 24 h Holter recordings revealed minor ischemic events in only 10% of patients with transient left ventricular apical ballooning. Overall, ST segment changes were not indicative of recurrent coronary spasm playing a major role in the genesis of transient left ventricular apical ballooning.     

Short-Term Effects of Particulate Matter on Stroke Attack: Meta-Regression and Meta-Analyses

Background and Purpose

Currently there are more and more studies on the association between short-term effects of exposure to particulate matter (PM) and the morbidity of stroke attack, but few have focused on stroke subtypes. The objective of this study is to assess the relationship between PM and stroke subtypes attack, which is uncertain now.

Methods

Meta-analyses, meta-regression and subgroup analyses were conducted to investigate the association between short-term effects of exposure to PM and the morbidity of different stroke subtypes from a number of epidemiologic studies (from 1997 to 2012).

Results

Nineteen articles were identified. Odds ratio (OR) of stroke attack associated with particular matter (“thoracic particles” [PM₁₀]<10 µm in aerodynamic diameter, “fine particles” [PM_2.5]<2.5 µm in aerodynamic diameter) increment of 10 µg/m³ was as effect size. PM₁₀ exposure was related to an increase in risk of stroke attack (OR per 10 µg/m³ = 1.004, 95%CI: 1.001∼1.008) and PM_2.5 exposure was not significantly associated with stroke attack (OR per 10 µg/m³ = 0.999, 95%CI: 0.994∼1.003). But when focused on stroke subtypes, PM_2.5 (OR per 10 µg/m³ = 1.025; 95%CI, 1.001∼1.049) and PM₁₀ (OR per 10 µg/m³ = 1.013; 95%CI, 1.001∼1.025) exposure were statistically significantly associated with an increased risk of ischemic stroke attack, while PM_2.5 (all the studies showed no significant association) and PM₁₀ (OR per 10 µg/m³ = 1.007; 95%CI, 0.992∼1.022) exposure were not associated with an increased risk of hemorrhagic stroke attack. Meta-regression found study design and area were two effective covariates.

Conclusion

PM_2.5 and PM₁₀ had different effects on different stroke subtypes. In the future, it''s worthwhile to study the effects of PM to ischemic stroke and hemorrhagic stroke, respectively.     

Hemodynamic Effects of Stent Struts versus Straightening of Vessels in Stent-Assisted Coil Embolization for Sidewall Cerebral Aneurysms

Background

Recent clinical studies have shown that recanalization rates are lower in stent-assisted coil embolization than in coiling alone in the treatment of cerebral aneurysms.

Objective

This study aimed to assess and compare the hemodynamic effect of stent struts and straightening of vessels by stent placement on reducing flow velocity in sidewall aneurysms, with the goal of reducing recanalization rates.

Methods

We evaluated 16 sidewall aneurysms treated with Enterprise stents. We performed computational fluid dynamics simulations using patient-specific geometries before and after treatment, with or without stent struts.

Results

Stent placement straightened vessels by a mean (±standard deviation) of 12.9°±13.1° 6 months after treatment. Placement of stent struts in the initial vessel geometries reduced flow velocity in aneurysms by 23.1%±6.3%. Straightening of vessels without stent struts reduced flow velocity by 9.6%±12.6%. Stent struts had significantly stronger effects on reducing flow velocity than straightening (P = 0.004, Wilcoxon test). Deviation of the effects was larger by straightening than by stent struts (P = 0.01, F-test). The combination of stent struts and straightening reduced flow velocity by 32.6%±12.2%. There was a trend that larger inflow angles produced a larger reduction in flow velocity by straightening of vessels (P = 0.16).

Conclusion

In sidewall aneurysms, stent struts have stronger effects (approximately 2 times) on reduction in flow velocity than straightening of vessels. Hemodynamic effects by straightening vary in each case and can be predicted by inflow angles of pre-operative vessel geometry. These results may be useful to design a treatment strategy for reducing recanalization rates.     

Drug-Eluting versus Bare-Metal Stent for Treatment of Saphenous Vein Grafts: A Meta-Analysis

Background

Saphenous vein grafts develop an aggressive atherosclerotic process and the efficacy of drug eluting stents (DES) in treating saphenous vein graft (SVG) lesions has not been convincingly demonstrated. The aim of this study was to review and analyze the current literature for controlled studies comparing DES versus bare metal stents (BMS) for treatment of SVG stenoses.

Methodology/Principal Findings

We searched several scientific databases and conference proceedings up to March 15, 2010 for controlled studies comparing target vessel revascularization (TVR) between DES and BMS. Summary odds ratios (OR) for the primary endpoint TVR and secondary endpoints infarction, stent thrombosis and death were calculated using random-effect models. A total of 29 studies (3 randomized controlled trials RCT) involving 7549 (202 in RCT) patients were included. The need for target vessel revascularization in the DES group tended to be lower compared to BMS for the 3 RCT (OR 0.50 [0.24–1.00]; p = 0.051) and for observational studies (0.62 [0.49–0.79]; p<0.001). There was no significant difference in the risk for myocardial infarction in the RCT (OR 1.25 [0.22–6.99]; p = 0.250) but a lower risk for DES based on the observational studies 0.68 [0.49–0.95]; p = 0.023. The risk for stent thrombosis was found to be non-different in the RCT (OR 0.78 [0.03–21.73], p = 0.885) while it was in favor of DES in the observational studies (0.58 [0.38 – 0.84]; p<0.001). The mortality was not significantly different between DES and BMS in the RCT''s (OR 2.22 [0.17 – 29.50]; p = 0.546) while the observation studies showed a decreased mortality in the DES group (0.69 [0.55–0.85]; p<0.001).

Conclusion

DES may decrease TVR rate in treatment of SVG stenoses. No differences in reinfarction rate, stent thrombosis or mortality was found between the DES and BMS groups in the RCT''s while the observational data showed lower risk for myocardial infarction, stent thrombosis and death in the DES group. This may be a result of patient selection bias in the observational studies or represent a true finding that was not the detected in the RCT analysis due to limited statistical power.     

Association of Residual Plasma Viremia and Intima-Media Thickness in Antiretroviral-Treated Patients with Controlled Human Immunodeficiency Virus Infection

Background

While residual plasma viremia is commonly observed in HIV-infected patients undergoing antiretroviral treatment (ART), little is known about its subclinical consequences.

Methods

This cross-sectional study included 47 male, never-smoking, non-diabetic patients with ≥4 years of ART and controlled HIV-replication (HIV-viral load, VL <20 copies/mL for ≥1 year). Residual HIV-VL was measured using an ultrasensitive assay (quantification limit: 1 copy/ml). Patients were categorized as having detectable (D; 1-20 copies/mL, n = 14) or undetectable (UD; <1 copies/mL, n = 33) HIV-VL. Linear regression was used to model the difference in total carotid intima-media thickness [c-IMT, measures averaged across common carotid artery (cca), bifurcation, and internal carotid artery] and cca-IMT alone across detection groups. Multivariable models were constructed for each endpoint in a forward-stepwise approach.

Results

No significant differences were observed between viremia groups with respect to median ART-duration (9.6 years, IQR = 6.8–10.9), nadir CD4+T-cell (208/mm³, IQR = 143–378), and CD4+T-cell count (555/mm³, IQR = 458–707). Median adjusted inflammatory markers tended to be higher in patients with D- than UD-viremia, with differences in IL-10 being significant (p = 0.03). After adjustment on age, systolic blood pressure, and insulin resistance, mean cca-IMT was significantly lower in patients with undetectable (0.668 mm±0.010) versus detectable viremia (0.727 mm±0.015, p = 0.002). Cca-IMT was also independently associated with age and insulin resistance. Mean adjusted total c-IMT was no different between viremia groups (p = 0.2), however there was large variability in bifurcation c-IMT measurements.

Conclusions

Higher cca-IMT was observed in patients with detectable, compared to undetectable, HIV-VL in never-smoking ART-controlled patients, suggesting that residual HIV viremia may be linked to atherosclerosis.     

Last Generation Triazoles for Imported Eumycetoma in Eleven Consecutive Adults

Background

Optimal management of eumycetoma, a severely debilitating chronic progressive fungal infection of skin, disseminating to bone and viscera, remains challenging. Especially, optimal antifungal treatment and duration are ill defined.

Methodology/Principal Findings

We conducted a monocentric retrospective study of 11 imported cases of eumycetoma treated by voriconazole or posaconazole for at least 6 months. Response to treatment was assessed through evolution of clinical and magnetic resonance imaging (MRI). (1→3) ß-D-glucan (BG) and positron emission tomography using [18F] fluorodeoxyglucose (PET/CT) results were also assessed. Identified species were Fusarium solani complex (n = 3); Madurella mycetomatis, (n = 3), and Exophiala jeanselmei, (n = 1). Moreover, two coelomycetes and one phaeohyphomycetes strains without species identification were retrieved. Serum BG and PET/CT were abnormal in 7/8 and 6/6 patients tested, respectively. Patients received last generation azoles for a mean duration of 25.9±18 months. Complete response (major clinical and MRI improvement) was observed in 5/11 patients, partial response (minor MRI improvement or stable MRI findings) in 5 and failure (MRI evidence of disease progression) in one, with a 73±39 [6–132] months mean follow-up. Relapse occurred in 2 patients after treatment discontinuation. Optimal outcome was associated with fungal species, initiation of last generation triazole therapy (<65 months since first symptoms), negative serum BG and PET/CT normalization.

Conclusions/Significance

MRI, PET/CT and serum BG appear as promising tools to assess optimal time of antifungal treatment for eumycetoma.     

Predictors of Mortality among Patients Enrolled on Antiretroviral Therapy in Aksum Hospital,Northern Ethiopia: A Retrospective Cohort Study

Background

Since launching of antiretroviral (ART) treatment, the numbers of patients enrolled in to ART are increasing in many developing countries. But many studies done across Africa including Ethiopia on antiretroviral therapy programs have shown higher mortality at the first six months of treatment initiation. But the factors associated with this high mortality are poorly characterized. So this study aims to determine mortality and identify predictors of it among patients on ART.

Methods

Retrospective cohort study was employed among a total of 520 records of patients who were enrolled on antiretroviral therapy in Aksum hospital from September 2006 to August 2011. Baseline patient records were extracted from electronic and paper based medical records database and analysed using Kaplan Meier survival and Cox proportional hazard model to identify the independent predictors of mortality of patients on ART.

Results

A total of 46 (8.85%) deaths was observed giving an overall mortality rate of 3.2 per 100 person-years. The independent predictor of mortality identified for this cohort were haemoglobin level <11 mg/dl (Hazard Ratio (HR) = 1.9, 95%-CI = 1.01, 3.52), CD4 cell counts lower than 50 cells/µl (HR = 2.1, 95%- CI = 1.13,3.89), Male gender (HR = 1.9, 95%-CI = 1.01,3.52), Weight <40 kg (HR = 2.3,95% CI = 1.24,4.55), primary level of education and lower (HR = 2.6, 95%- CI = 1.29,5.55).

Conclusions

The over all mortality of adults patients on ART was low but higher in the early months of ART initiation. low levels of haemoglobin <11 gm/dl, lower CD4 cell count, male gender, weight <40 Kg and individuals who have primary level of education and lower were indentified as the independent predictors of mortality. For this reason, early initiation of ART despite the CD4 count and method of HIV diagnosis, nutritional support and close monitoring of patients in the early periods of ART treatment initiation is very crucial to improve patient survival.     

Therapeutic Vaccination with TNF-Kinoid in TNF Antagonist-Resistant Rheumatoid Arthritis: A Phase II Randomized,Controlled Clinical Trial

Objectives

Active immunization, or vaccination, with tumor necrosis factor (TNF)-Kinoid (TNF-K) is a novel approach to induce polyclonal anti-TNF antibodies in immune-mediated inflammatory diseases. This study was performed to transfer the proof of concept obtained in mice model of rheumatoid arthritis (RA) into human. We designed a pilot study to demonstrate the feasibility of therapeutic vaccination in RA.

Methods

This was a phase IIa, placebo-controlled, multicenter study in adults with RA who previously experienced secondary failure of TNF antagonists. Patients were immunized intramuscularly with 2 or 3 doses of placebo (n = 10) or 90 (n = 6), 180 (n = 12), or 360 µg TNF-K (n = 12). The primary objective was to identify the best dose and schedule based on anti-TNF antibody titers. Clinical symptoms and safety were assessed during 12 months and solicited reactions for 7 days after each injection.

Results

The highest anti-TNF antibody response was detected in patients immunized with 360 µg TNF-K and with 3 injections, although this difference was not significant with all other groups. Similar proportions of patients receiving TNF-K and placebo reported adverse events up to month 12. Serious adverse events were reported by 4 patients treated with TNF-K (13.3%) and 3 treated with placebo (30.0%), all unrelated to treatment. At month 12, DAS28-CRP, tender and swollen joint counts, and HAQ scores decreased significantly more in patients who exhibited anti-TNF antibody response than in patients who did not.

Conclusions

TNF-K therapeutic vaccination induced dose- and schedule-dependent anti-TNF antibodies in RA patients and was well tolerated. Patients who developed anti-TNF antibodies showed a trend toward clinical improvement. Although the most aggressive dose and schedule, i.e. 360 mg dose administered 3 times, did show a strong trend of higher antibody response, further studies are warranted to examine even higher and more frequent doses in order to establish the best conditions for clinical improvement.

Trial Registration

ClinicalTrials.gov NCT01040715