Cytokines as effectors and predictors of responses in the treatment of bladder cancer by bacillus Calmette-Guérin.

The most effective intravesical treatment of non-muscle-invasive bladder cancer is instillation of live Mycobacterium bovis bacillus Calmette-Guérin (BCG). BCG stimulates the release of cytokines, contributing directly or indirectly to its effectiveness. However, the function of specific cytokines is not well understood. We have undertaken a nonsystematic review of primary evidence regarding cytokine detection, activation and response in BCG patients. Cytokines IL-2, IL-8 and TNF-α appear to be essential for effective BCG therapy and nonrecurrence, while IL-10 may have an inhibitory effect on BCG responses. IL-2, IL-8, TRAIL and TNF-α are potentially predictive of response to BCG. Alterations in genes encoding cytokines may also affect responses. There are significant data showing the association of certain cytokines with successful BCG treatment, and which may be useful predictive markers. Isolating those cytokines mediating efficacy may hold the key to ameliorating BCG's side effects and improving efficacy and patient compliance.

Prevalence of Rheumatic Heart Disease and Other Cardiac Conditions in Low-Risk Pregnancies in Kenya: A Prospective Echocardiography Screening Study.

Background: Rheumatic heart disease (RHD) in sub-Saharan Africa contributes to significant cardiac morbidity and mortality, yet prevalence estimates of RHD lesions in pregnancy are lacking. Objectives: Our first aim was to evaluate women using echocardiography to estimate the prevalence of RHD and other cardiac lesions in low-risk pregnancies. Our second aim was to assess the feasibility of screening echocardiography and its acceptability to patients. Methods: We prospectively recruited 601 pregnant women from a low-risk antenatal clinic at a tertiary care maternity centre in Western Kenya. Women completed a questionnaire about past medical history and cardiac symptoms. They underwent standardized screening echocardiography to evaluate RHD and non-RHD associated cardiac lesions. Our primary outcome was RHD-associated cardiac lesions and our secondary outcome was a composite of any clinically-relevant cardiac lesion or echocardiography finding. We also recorded duration of screening echocardiography and its acceptability among pregnant women in this sample. Results: The point prevalence of RHD-associated cardiac lesions was 5.0/1,000 (95% confidence interval: 1.0-14.5), and the point prevalence of all clinically significant lesions/findings was 21.6/1,000 (11.6-36.7). Mean screening time was seven minutes (SD 1.7, range: 4-17) for women without cardiac abnormalities and 13 minutes (SD 4.6, range: 6-23) for women with abnormal findings. Echocardiography was acceptable to women with 74.2% agreeing to participate. Conclusions: The prevalence of clinically-relevant cardiac lesions was moderately high in a low-risk population of pregnant women in Western Kenya.

Analysis of the long-term effects of drug-eluting stents on coronary arterial wall morphology as assessed by virtual histology intravascular ultrasound.

BACKGROUND: Animal models show impairment of arterial healing after drug-eluting stents (DES) compared with bare-metal stents (BMS). Virtual histology intravascular ultrasound (VH-IVUS) offers an opportunity to assess lesion morphology in vivo. METHODS: We used VH-IVUS in 80 patients to assess long-term (median = 10 months) native artery vascular responses after 76 implantations of DES compared with 32 BMS. The presence of "necrotic core abutting the lumen" was evaluated at baseline and follow-up. RESULTS: At baseline, necrotic core abutting the lumen through the stent struts was observed in 76% of DES and 75% of BMS. Although the percentage of necrotic core within the plaque behind the stents did not change during follow-up in DES (23% [18%, 28%] to 22% [17%, 27%], P = .57) or BMS (22% [19%, 27%] to 20% [12%, 26%], P = .29), necrotic core abutting the lumen through the stent struts decreased more in BMS (75% to 19%, P < .001) than DES (76% to 61%, P = .036) because of the lack of an overlying, protective neointima in DES-treated lesions. Furthermore, within the adjacent reference segments, the incidence of necrotic core abutting the lumen decreased in BMS-treated lesions (proximal 23% to 0%, P = .023; distal 21% to 0%, P = .023), but not in DES (proximal 22% to 17%, P = .48; distal 23% to 21%, P = .82). CONCLUSIONS: Serial VH-IVUS analysis of DES-treated lesions showed a greater frequency of unstable lesion morphometry at follow-up compared with BMS. The apparent mechanism was a suppression of the protective neointimal hyperplasia layer coupled with a lack of vulnerable plaque resolution at reference segments in DES compared with BMS.

Improving on the diagnostic characteristics of echocardiography for pulmonary hypertension.

This retrospective study evaluated the diagnostic characteristics of a combination of echocardiographic parameters for pulmonary hypertension (PH). Right ventricular systolic pressure (RVSP) estimation by echocardiography (echo) is used to screen for PH. However, the sensitivity of this method is suboptimal. We hypothesized that RVSP estimation in conjunction with other echo parameters would improve the value of echo for PH. The Duke Echo database was queried for adult patients with known or suspected PH who had undergone both echo and right heart catheterization (RHC) within a 24 h period between 1/1/2008 and 12/31/2013. Patients with complex congenital heart disease, heart transplantation, ventricular assist device, or on mechanical ventilation at time of study were excluded. Diagnostic characteristics of several echo parameters (right atrial enlargement, pulmonary artery (PA) enlargement, RV enlargement, RV dysfunction, and RVSP) for PH (mean PA pressure 25 mmHg on RHC) were evaluated among 1007 patients. RVSP ≥40 had a sensitivity of 77% (accuracy 77), while RVSP ≥35 had the highest sensitivity at 88% (81% accuracy). PA enlargement had the lowest sensitivity at 17%. The area under the curve (AUC) for RVSP was 0.844. A model including RVSP, RA, PA, RV enlargement and RV dysfunction had a higher AUC (AUC = 0.87) than RVSP alone. The value of echo as a screening test for PH is improved by a model incorporating a lower RVSP in addition to other right heart parameters. These findings need to be validated in prospective cohorts.

Building Sustainable Capacity for Cardiovascular Care at a Public Hospital in Western Kenya.

Cardiovascular disease deaths are increasing in low- and middle-income countries and are exacerbated by health care systems that are ill-equipped to manage chronic diseases. Global health partnerships, which have stemmed the tide of infectious diseases in low- and middle-income countries, can be similarly applied to address cardiovascular diseases. In this review, we present the experiences of an academic partnership between North American and Kenyan medical centers to improve cardiovascular health in a national public referral hospital. We highlight our stepwise approach to developing sustainable cardiovascular services using the health system strengthening World Health Organization Framework for Action. The building blocks of this framework (leadership and governance, health workforce, health service delivery, health financing, access to essential medicines, and health information system) guided our comprehensive and sustainable approach to delivering subspecialty care in a resource-limited setting. Our experiences may guide the development of similar collaborations in other settings.

Relation between angiographic lesion severity, vulnerable plaque morphology and future adverse cardiac events (from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree study).

Previous angiographic studies have suggested that the future risk for major adverse cardiovascular events (MACEs) is related to coronary stenosis severity. The aim of this study was to use the grayscale and virtual histology (VH)-intravascular ultrasound (IVUS) data from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study to identify underlying lesion morphologic characteristics that might explain these findings. In PROSPECT, patients presenting with acute coronary syndromes in whom percutaneous coronary intervention was successful underwent 3-vessel grayscale and VH-IVUS and were followed for a median of 3.4 years for the incidence of MACEs. Overall, 3,115 nonculprit lesions detected by IVUS were divided into quartiles according to baseline angiographic diameter stenosis. From the first to fourth quartiles, there were increases in the prevalence of lesions with IVUS minimum luminal areas ≤ 4 mm(2), IVUS plaque burden ≥ 70%, and VH-IVUS thin-cap fibroatheroma (13.4%, 22.0%, 24.2%, and 30.3%, respectively, p <0.001), along with an increased frequency of plaque ruptures and greater necrotic core volumes. The incidence of lesions with plaque burden ≥ 70%, minimum luminal area ≤ 4 mm(2), and VH thin-cap fibroatheroma was highest in the fourth quartile (0%, 0.4%, 0.4%, and 2.8% in the first through fourth quartiles, respectively, p <0.001). Three-year MACE rates were also highest in the fourth quartile (0.3%, 0.7%, 1.3%, and 5.1%, respectively, p <0.001). In conclusion, increasing angiographic diameter stenosis was associated with an increased frequency of grayscale and VH-IVUS lesion morphologic features that have been associated with adverse events and that may, in part, explain why future MACEs were related to baseline lesion severity.

Clinical and angiographic outcomes after treatment of de novo coronary stenoses with a novel platinum chromium thin-strut stent: primary results of the PERSEUS (Prospective Evaluation in a Randomized Trial of the Safety and Efficacy of the Use of the TAXUS Element Paclitaxel-Eluting Coronary Stent System) trial.

OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of the novel platinum chromium TAXUS Element paclitaxel-eluting stent (PES) compared with the TAXUS Express PES (Boston Scientific, Natick, Massachusetts) in treating coronary artery stenoses. BACKGROUND: The TAXUS Element is a novel thin-strut (81 microm), platinum chromium alloy PES designed to improve radial strength, radiopacity, and deliverability, while safely providing comparable restenosis benefit compared with a previous-generation PES. METHODS: The PERSEUS (Prospective Evaluation in a Randomized Trial of the Safety and Efficacy of the Use of the TAXUS Element Paclitaxel-Eluting Coronary Stent System) Workhorse (WH) trial is a prospective, randomized (3:1), controlled, multicenter study of the TAXUS Element (vs. TAXUS Express) PES for the treatment of de novo coronary atherosclerotic lesionsor=2.75 to

Randomized, placebo-controlled trial showing that finasteride reduces prostatic vascularity rapidly within 2 weeks.

OBJECTIVE: To measure expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in the prostates of men after transurethral resection of the prostate (TURP) following 2 weeks of treatment with finasteride. PATIENTS AND METHODS: Sixty-four men scheduled to undergo TURP were randomized to receive 5 mg of finasteride or placebo daily for 2 weeks before surgery. Sections of prostatic urothelium were stained for VEGF expression and for CD31 to assess MVD. Ten consecutive, non-overlapping high-power fields were analysed in a blinded fashion. RESULTS: In all, 31 men received finasteride and 33 placebo; the groups were similar in patient age, resected prostate weight, preoperative catheterization, prostate-specific antigen level, aspirin use, spinal anaesthesia and postoperative diagnosis of prostate cancer. The mean (95% confidence interval) MVD was significantly lower in the finasteride group (60, 55-65) than in the placebo group (71, 64-78; P < 0.01). Similarly, the mean expression of VEGF was significantly lower in the finasteride group (47, 43-52 vs 61, 54-67; P < 0.001) CONCLUSION: Finasteride inhibits angiogenic growth factors leading to reduced vascularity, and this is the basis of its action in reducing haematuria of prostatic origin. The present study shows that finasteride influences the prostatic microvasculature after only 2 weeks exposure.