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Biomedical subjects

Andrew Wang

Publications and source records attributed to Andrew Wang.

At least 19 recordsLinked to original sources
PubMed2007

Early surgery in patients with infective endocarditis: a propensity score analysis.

BACKGROUND: An accurate assessment of the predictors of long-term mortality in patients with infective endocarditis is not possible using retrospective data because of inherent treatment biases and predictable imbalances in the distribution of prognostic factors. Largely because of these limitations, the role of surgery in long-term survival has not been adequately studied. METHODS: Data were collected prospectively from 426 patients with infective endocarditis. Variables associated with surgery in patients who did not have intracardiac devices who had left-side-associated valvular infections were determined using multivariable analysis. Propensity scores were then assigned to each patient based on the likelihood of undergoing surgery. Using individual propensity scores, 51 patients who received medical and surgical treatment were matched with 51 patients who received medical treatment only. RESULTS: The following factors were statistically associated with surgical therapy: age, transfer from an outside hospital, evidence of infective endocarditis on physical examination, the presence of infection with staphylococci, congestive heart failure, intracardiac abscess, and undergoing hemodialysis without a chronic catheter. After adjusting for surgical selection bias by propensity score matching, regression analysis of the matched cohorts revealed that surgery was associated with decreased mortality (hazard ratio, 0.27; 95% confidence interval, 0.13-0.55). A history of diabetes mellitus (hazard ratio, 4.81; 95% confidence interval, 2.41-9.62), the presence of chronic intravenous catheters at the beginning of the episode (hazard ratio, 2.65; 95% confidence interval, 1.31-5.33), and paravalvular complications (hazard ratio, 2.16; 95% confidence interval, 1.06-4.44) were independently associated with increased mortality. CONCLUSIONS: Differences between clinical characteristics of patients with infective endocarditis who receive medical therapy versus patients who receive surgical and medical therapy are paramount. After controlling for inherent treatment selection bias and imbalances in prognostic factors using propensity score methodology, risk factors associated with increased long-term mortality included diabetes mellitus, the presence of a chronic catheter at the onset of infection, and paravalvular complications. In contrast, surgical therapy was associated with a significant long-term survival benefit.

Adult↗
PubMed2006

Etanercept induces apoptosis of dermal dendritic cells in psoriatic plaques of responding patients.

BACKGROUND: Etanercept is a tumor necrosis factor-alpha binding fusion protein that demonstrates efficacy in the treatment of psoriasis, which is accompanied by decreased plaque infiltration of T cells and myeloid dendritic cells. We hypothesized that etanercept decreases inflammatory cell infiltration by inducing apoptosis. OBJECTIVE: We sought to investigate the effect of etanercept on circulating and plaque leukocyte apoptosis in psoriasis. METHODS: Blood and plaque specimens were obtained from 10 patients with psoriasis treated with etanercept (25 mg subcutaneously twice weekly) for 24 weeks. Apoptosis was determined in tissue samples using immunohistochemistry and flow cytometry. RESULTS: Etanercept selectively induced apoptosis in dermal dendritic cells in plaques of responding patients at 1 month, before most of the clinical and histologic response was achieved. No apoptosis was detected in plaque or circulating T cells or in circulating monocytes. LIMITATIONS: Addition of multiple time points earlier than 1 month would be valuable to establish the time point of maximum induction in cell apoptosis. CONCLUSION: Etanercept selectively induces apoptosis of pathogenic dermal dendritic cells in responding patients early in the course of treatment.

Adolescent↗
PubMed2006

A Tlr7 translocation accelerates systemic autoimmunity in murine lupus.

The y-linked autoimmune accelerating (yaa) locus is a potent autoimmune disease allele. Transcription profiling of yaa-bearing B cells revealed the overexpression of a cluster of X-linked genes that included Tlr7. FISH analysis demonstrated the translocation of this segment onto the yaa chromosome. The resulting overexpression of Tlr7 increased in vitro responses to Toll-like receptor (TLR) 7 signaling in all yaa-bearing males. B6.yaa mice are not overtly autoimmune, but the addition of Sle1, which contains the autoimmune-predisposing Slam/Cd2 haplotype, causes the development of fatal lupus with numerous immunological aberrations. B6.Sle1yaa CD4 T cells develop the molecular signature for T(FH) cells and also show expression changes in numerous cytokines and chemokines. Disease development and all component autoimmune phenotypes were inhibited by Sles1, a potent suppressor locus. Sles1 had no effect on yaa-enhanced TLR7 signaling in vitro, and these data place Sles1 downstream from the lesion in innate immune responses mediated by TLR7, suggesting that Sles1 modulates the activation of adaptive immunity in response to innate immune signaling.

Animals↗
PubMed2006

Low-molecular-weight heparin for thromboprophylaxis in pregnant women with mechanical heart valves.

BACKGROUND: Pregnancy in a woman with a mechanical heart valve is a life-threatening situation. Due to the inability of unfractionated heparin to prevent valvular thromboses, warfarin or other vitamin K antagonists have been the preferred anticoagulants for the mother. They are, however, potentially harmful to the fetus. With the advent of low-molecular-weight heparins, clinicians were hopeful for an alternative that was safe for the fetus, but more effective than unfractionated heparin, which carries a 29-33% risk of life-threatening thromboses and a 7-15% chance of mortality. Unfortunately, fatal thromboses have occurred with low-molecular-weight heparin as well. METHODS: We searched the MEDLINE database and other sources to identify cases of the use of low-molecular-weight heparin for thromboprophylaxis in women with mechanical heart valves. RESULTS: We found 73 cases and added three of our own for a total of 76. There were 17 thrombotic events (22%). Thirteen were valve thromboses, two were strokes, and two were myocardial infarctions. There were three deaths (4%). CONCLUSIONS: While pregnant women with mechanical heart valves who receive low-molecular-weight heparin for thromboprophylaxis are at extremely high risk of life-threatening thromboses, there is no evidence that low-molecular-weight heparin is inferior to unfractionated heparin.

Anticoagulants↗
PubMed2006

Peripheral blood levels of matrix metalloproteinases in patients referred for percutaneous balloon mitral valve commissurotomy.

BACKGROUND AND AIM OF THE STUDY: Inflammation may play a central role in the progression of stenotic valvular heart disease. Serum levels of matrix metalloproteinases (MMPs), markers of extracellular matrix (ECM) turnover and potential markers of active inflammation, have been recently demonstrated in several inflammatory processes. The present study was designed to examine whether systemic evidence of ECM turnover was present in advanced stenotic mitral valve disease. METHODS: Serum levels of MMP-1, -3 and -9 were measured in 114 patients with mitral stenosis referred for percutaneous balloon mitral valve commissurotomy, and compared to those in 48 healthy, age- and gender-matched controls. RESULTS: Serum levels of MMP-1, -3 and -9 did not vary according to hemodynamic profile or heart failure class at the time of blood sampling. Levels of MMP-1 and -3 were not significantly different between those patients with mitral stenosis and controls. The level of MMP-9 was significantly higher in patients with mitral stenosis than in controls, and did not appear to be altered by commissurotomy. CONCLUSION: Serum levels of MMP-9 were elevated in patients with mitral stenosis, providing further evidence that inflammation and ECM remodeling plays an important role in the pathophysiology of valvular heart disease.

Adult↗
PubMed2005

Clinical characteristics and outcome of aortic endocarditis with periannular abscess in the International Collaboration on Endocarditis Merged Database.

The aims of this study were to determine the clinical characteristics and outcome of patients who had definite infective endocarditis (IE) complicated by aortic ring abscess formation that was detected with transesophageal echocardiography (TEE) and to determine the prognostic significance of abscess formation in aortic valve IE. Patients who had aortic valve IE were selected from the International Collaboration on Endocarditis Merged Database (ICE-MD) if they underwent TEE. Among 311 patients who had definite aortic valve IE, 67 (22%) had periannular abscesses. They were more likely to have infection in the setting of a prosthetic valve (40% vs 19%, p <0.001) and coagulase-negative staphylococcal IE (18% vs 6%, p < 0.01) and less likely to have streptococcal IE than were patients who did not develop abscess (28% vs 46%, p = 0.01). Systemic embolization, central nervous system events, and heart failure did not differ between those who developed abscess and those who did not, but power was limited. Patients who had abscess were more likely to undergo surgery (84% vs 36%, p <0.001), and their in-hospital mortality rate was higher (19% vs 11%, p = 0.09). Multivariate analysis of prognostic factors of mortality in aortic IE identified age (odds ratio [OR] 1.6, 95% confidence interval [CI]1.2 to 2.1), Staphylococcus aureus (S. aureus) infection (OR 2.4, 95% CI 1.1 to 5.2), and heart failure (OR 2.9, 95% CI 1.4 to 6.1) as variables that were independently associated with increased risk of death. Periannular abscess formation showed a nonsignificant trend toward an increased risk of death (OR 1.9, 95% CI 0.9 to 3.8). Multivariate analysis of prognostic factors of mortality in complicated aortic IE with abscess formation identified S. aureus infection (OR 6.9, 95% CI 1.6 to 29.4) as independently associated with increased risk of death. In conclusion, in the current era of TEE and high use of surgical treatment, periannular abscess formation in aortic valve IE is not an independent risk factor for mortality. S. aureus infection is an independent prognostic factor for mortality in patients who have abscess formation.

Abscess↗
PubMed2005

Differential effects of vascular endothelial growth factor receptor-2 inhibitor ZD6474 on circulating endothelial progenitors and mature circulating endothelial cells: implications for use as a surrogate marker of antiangiogenic activity.

PURPOSE: Circulating endothelial cells (CEC) comprise at least two distinct populations: bone marrow-derived circulating endothelial progenitors (CEP) and mature CECs derived from existing vasculature. We hypothesized that antiangiogenic agents may have differential effects on CEPs and mature CECs and that these changes may serve as a marker of biological activity. EXPERIMENTAL DESIGN: The effect of angiogenesis inhibitors on CECs was evaluated by flow cytometry after vascular endothelial growth factor (VEGF)-induced mobilization and in mice bearing Lewis lung carcinoma (LLC). Tumor angiogenesis was evaluated in parallel by immunohistochemistry. RESULTS: In nontumor-bearing mice, VEGF administration increased both mature CECs and CEPs. This increase was inhibited by the VEGF receptor 2 inhibitor ZD6474 as well as the VEGF inhibitor-soluble Flt-1. ZD6474 had no significant effect on CECs in the absence of exogenous VEGF stimulation. In contrast, LLC-bearing mice had an increase in mature CECs but not CEPs after 3 days of treatment with ZD6474. The increase in mature CECs was dose-dependent, accompanied by a decrease in tumor microvessel density, and preceded reduction in tumor volume. Treatment of LLC-bearing mice with the vascular targeting agent ZD6126 also increased mature CECs. CONCLUSIONS: VEGF inhibitors can have differential effects on mature CECs and CEPs, and agents inhibiting tumor angiogenesis may cause a concomitant increase in mature CECs. This increase occurs in tumor-bearing but not in nontumor-bearing mice, suggesting that tumor endothelium is a potential source of mature CECs. Therefore, assessing both mature CECs and CEPs may provide insights into the mechanism of antiangiogenic agents and serve as an early surrogate marker of biological activity.

Animals↗
PubMed2005

The response to inhaled nitric oxide in patients with pulmonary artery hypertension is not masked by baseline vasodilator use.

BACKGROUND: Assessment of pulmonary vasodilator responsiveness is important in determining the prognosis and management of patients with pulmonary hypertension. Many patients, however, are already on vasodilators at the time of testing. It is unclear if these agents should be temporarily discontinued to improve the sensitivity of testing. METHODS: We examined the hemodynamic effects of nitric oxide (NO) inhalation in 60 patients with pulmonary arterial hypertension. Thirty-one of these patients were receiving medications with vasodilating properties. Vasodilator testing was performed with invasive measurement of pressure of the right side of the heart at baseline and during inhalation of 40 ppm NO. RESULTS: No significant demographic differences were seen between patients receiving and not receiving vasodilators. Similar reductions in mean pulmonary artery pressure (19 +/- 12% vs 20 +/- 12%, P = .734) and pulmonary vascular resistance (31 +/- 18 vs 32 +/- 16, P = .967) were seen in patients receiving and not receiving vasodilators. Using the definition of positive vasodilator response (> or = 20% drop in mean pulmonary artery pressure), 55% (17/31) of patients in the baseline vasodilator group had a positive response compared with 62% (18/29) of the patients not on vasodilators (P = .570). CONCLUSIONS: Concurrent use of oral vasodilators does not appear to mask a significant response to inhaled NO on the pulmonary vasculature. Therefore, routine discontinuation of pulmonary vasodilators is likely unnecessary before vasodilator testing in patients with pulmonary arterial hypertension.

Administration, Inhalation↗
PubMed2005

The use and effect of surgical therapy for prosthetic valve infective endocarditis: a propensity analysis of a multicenter, international cohort.

BACKGROUND: Although surgical intervention is often used in the treatment of prosthetic valve infective endocarditis (PVIE), an understanding of its effect on survival has been limited by the biases of observational studies and lack of controlled trials. METHODS: The International Collaboration on Endocarditis Merged Database is a large, multicenter, international registry of patients with definite endocarditis by Duke criteria, including 367 patients with PVIE. Clinical, microbiologic, and echocardiographic variables were analyzed to determine those factors associated with the use of surgery for PVIE. Logistic regression analysis was performed to create a propensity model of predictors of surgery use. Patients who underwent surgery during initial hospitalization were matched by propensity score with patients treated with medical therapy alone. Logistic regression analysis was performed to determine variables independently associated with inhospital mortality in this matched subset. RESULTS: Surgical therapy for PVIE was performed in 148 (42%) of 367 patients. Inhospital mortality was similar for patients treated with surgery compared with those treated with medical therapy alone (25.0% vs 23.4%, P = .729). Surgical therapy was independently associated with patient age, microorganism, intracardiac abscess, and congestive heart failure. After adjustment for these determinants, inhospital mortality was predicted by brain embolization (OR 11.12, 95% CI 4.16-29.73) and Staphylococcus aureus infection (OR 3.67, 95% CI 1.29-9.74), with a trend toward benefit for surgery (OR 0.56, 95% CI 0.23-1.36). CONCLUSIONS: Despite the frequent use of surgery for the treatment of PVIE, this condition continues to be associated with a high inhospital mortality rate in the contemporary era. After adjustment for factors related to surgical intervention, brain embolism and S aureus infection were independently associated with inhospital mortality and a trend toward a survival benefit of surgery was evident.

Aged↗
PubMed2005

Use of surgery in patients with native valve infective endocarditis: results from the International Collaboration on Endocarditis Merged Database.

BACKGROUND: Early surgery has been shown to be beneficial for patients with infective endocarditis (IE), yet surgery is not used in most patients. Evidence of the uncertainty around the use of surgery can be found in the wide variations in the use of cardiac surgery in IE with few precise indications for cardiac surgery yet defined. The aim of the study was to characterize patients with native valve IE relative to surgery and to determine if patients who benefit from an early surgical intervention can be identified. METHODS: The International Collaboration on Endocarditis Merged Database was used to quantify the differences between patients with IE receiving medical and surgical intervention in 1516 patients with definite native valve IE. Propensity models were built to identify a group of patients that benefit from early surgery. RESULTS: Patients in the early surgical group were more likely to be male, younger, and with less comorbidities compared with the early medical group (P < .001 for all) and were less likely to have infection with Staphylococcus aureus or viridans group streptococci (P < .05 for all). Intracardiac abscess and heart failure were much more common in the surgical group (P < .001 for all). In an unadjusted comparison, there was no statistically significant survival advantage in the surgical group. However, in the propensity analysis, in the subgroup of patients with the most indications for surgery, there was a significant decrease in mortality associated with early surgery (11.2% vs 38.0%, P < .001). CONCLUSIONS: The benefits of surgery are not seen uniformly in all patients with native valve IE, but are most realized in a targeted population. This observation requires confirmation in other populations of patients with definite IE.

Endocarditis, Bacterial↗
PubMed2005

Risk of endocarditis among patients with prosthetic valves and Staphylococcus aureus bacteremia.

PURPOSE: Staphylococcus aureus is a common cause of bacteremia and of native valve infective endocarditis. However, the risk of endocarditis in patients with a prosthetic valve who develop S. aureus bacteremia is unclear. The aim of this study was to define the risk of prosthetic valve endocarditis in patients with S. aureus bacteremia. SUBJECTS AND METHODS: All patients with a prosthetic valve or ring who developed S. aureus bacteremia during the 94-month study period were prospectively evaluated. The modified Duke criteria were used for the diagnosis of endocarditis. Patients were followed up for 12 weeks after the initial diagnosis of S. aureus bacteremia. RESULTS: The overall rate of definite prosthetic valve endocarditis among the study patients was 26/51 (51%). The risk of endocarditis was similar in patients with late (>or=12 months after valve implantation) vs. early S. aureus bacteremia (<12 months after prosthetic valve implantation) (50% vs. 52%, P=1.0), mitral vs. aortic prostheses (62% vs. 48%, P=0.24), and mechanical vs. bioprosthetic valves (62% vs. 44%, P=0.29). The 12-week mortality was higher among patients with definite vs. possible endocarditis (62% vs. 28%, P=0.019). CONCLUSION: In this investigation, approximately half of all patients with prosthetic valves who developed S. aureus bacteremia had definite endocarditis. The risk of endocarditis was independent of the type, location, or age of the prosthetic valve. The mortality of prosthetic valve endocarditis is high. All patients with a prosthetic valve who develop S. aureus bacteremia should be aggressively screened and followed for endocarditis.

Bacteremia↗
PubMed2004

HLA-B27 in transgenic rats forms disulfide-linked heavy chain oligomers and multimers that bind to the chaperone BiP.

To test the hypothesis that HLA-B27 predisposes to disease by forming disulfide-linked homodimers, we examined rats transgenic for HLA-B27, mutant Cys(67)Ser HLA-B27, or HLA-B7. In splenic Con A blasts from high transgene copy B27 lines that develop inflammatory disease, the anti-H chain mAb HC10 precipitated four bands of molecular mass 78-105 kDa and additional higher molecular mass material, seen by nonreducing SDS-PAGE. Upon reduction, all except one 78-kDa band resolved to 44 kDa, the size of the H chain monomer. The 78-kDa band was found to be BiP/Grp78, and the other high molecular mass material was identified as B27 H chain. Analysis of a disease-resistant low copy B27 line showed qualitatively similar high molecular mass bands that were less abundant relative to H chain monomer. Disease-prone rats with a Cys(67)Ser B27 mutant showed B27 H chain bands at 95 and 115 kDa and a BiP band at 78 kDa, whereas only scant high molecular mass bands were found in cells from control HLA-B7 rats. (125)I-surface labeled B27 oligomers were immunoprecipitated with HC10, but not with a mAb to folded B27-beta(2)-microglobulin-peptide complexes. Immunoprecipitation of BiP with anti-BiP Abs coprecipitated B27 H chain multimers. Folding and maturation of B27 were slow compared with B7. These data indicate that disulfide-linked intracellular H chain complexes are more prone to form and bind BiP in disease-prone wild-type B27 and B27-C67S rats than in disease-resistant HLA-B7 rats. The data support the hypothesis that accumulation of misfolded B27 participates in the pathogenesis of B27-associated disease.

Animals↗
PubMed2004

Usefulness of percutaneous balloon mitral commissurotomy in preventing the development of atrial fibrillation in patients with mitral stenosis.

A prospective cohort of patients with mitral stenosis and no history of atrial arrhythmias showed no decrease in the incidence of atrial fibrillation (AF) after successful versus unsuccessful Inoue balloon percutaneous balloon mitral valve commissurotomy. Advanced age and left atrial dimension best predicted which patients developed AF during follow-up, whereas percutaneous balloon mitral valve commissurotomy procedural success and left atrial pressure reduction did not have an impact on incidence of AF.

Adult↗
PubMed2004

Early predictors of in-hospital death in infective endocarditis.

BACKGROUND: Data on early determinants of outcome in infective endocarditis (IE) are limited. We evaluated the prognostic significance of early clinical characteristics in a large, prospective cohort of patients with IE. METHODS AND RESULTS: Two hundred sixty-seven consecutive patients with definite or possible IE by modified Duke criteria and echocardiography performed within 7 days of presentation were evaluated. Acute physiology was assessed by the Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) score at the time of presentation, and early heart failure was diagnosed by Framingham criteria. In-hospital mortality rate in the cohort was 19% and similar for patients with definite or possible IE (20% versus 16%, respectively; P=0.464). Independent predictors of death determined by logistic regression modeling were diabetes mellitus (OR 2.48; 95% CI, 1.24 to 4.96), Staphylococcus aureus as causative organism (OR, 2.06; 95% CI, 1.01 to 4.20), APACHE II score (OR, 1.07; 95% CI, 1.01 to 1.12), and embolic event (OR, 2.79; 95% CI, 1.15 to 6.80). Early echocardiographic findings of the Duke criteria were not predictive of death. CONCLUSIONS: Early in the course of IE, readily available clinical characteristics that reflect the host-pathogen interaction are predictive of in-hospital death. These factors may identify those patients with IE for more aggressive treatment.

APACHE↗
PubMed2004

Current Treatment Options for Patients with Endocarditis: The Evolving Indications for Cardiac Surgery.

Infective endocarditis (IE) is a serious and deadly disease. Despite medical advances over the past half century, more than one half of patients with IE suffer a serious complication, and the mortality rate remains approximately 20% during the initial hospitalization and approaches 40% at 1 year. In patients with documented IE, the treatment centers on two main aspects: effective antibiotic therapy and consideration of surgical therapy. Effective antibiotic therapy is the mainstay of treatment and focuses on sustained bactericidal concentrations tailored specifically to the causative microorganism. Surgical therapy is also an important option for many patients with IE. The goals of surgical therapy are to eradicate the focus of infection, to repair endocardial destruction, and to prevent the development of complications and relapse of infection. Ideally, surgical therapy should offer a survival advantage over medical therapy alone. Recent evidence supports the survival benefit of surgery in patients with IE, specifically in those with heart failure and complicated, left-sided IE. Future therapeutic strategies may include broader indications for surgery, as well as new treatments such as immune-modulating agents.

Journal Article↗