Long-term outcomes of high-risk elderly male patients with multivessel coronary disease： optimal medical therapy versus revascularization

Background Many studies have indicated that medical therapy and percutaneous coronary intervention have similar effects in terms of the long-term prognosis of patients with stable coronary artery disease. This study investigated the effects of optimal medical therapy （OMT） and revascularization-plus-OMT in elderly patients with high-risk angina. Methods In this prospective non-randomized study, 241 consecutive high-risk elderly male patients （65-92 years of age） with angiographically confirmed multivessel disease were enrolled in the registry from January 2004 to April 2005. Of these, 98 patients underwent OMT and 143 underwent revascularization therapy plus OMT. Results After 6.5 years of follow-up, we found that the rate of long-term cardiac mortality was significantly higher in patients who under- went OMT than in those who underwent revascularization （6.5-year unadjusted mortality rate, 14.3% for OMT vs. 7.0% for revascularization patients; log-rank P = 0.04）. However, the overall risks of major adverse cardiac cerebrovascular events （MACCE） were similar among all patients （6.5-year unadjusted mortality rate, 29.6% for OMT vs. 27.3% for revascularization patients; log-rank P = 0.67）. Conclusions OMT was associated with an increase in cardiac death but a similar 6.5-year risk of MACCE compared with revascularization in high-risk elderly male patients with coronary multivessel disease.

The impact of optimal medical therapy at discharge on mortality in patients with coronary artery disease

Objective To analyze the current usage of optimal medical therapy （OMT）, influencing factors, and the predictive value of OMT for all-cause mortality in coronary artery disease （CAD） patients with different subgroups. Methods A total of 3176 CAD patients confirmed by coronary angiography were included. OMT was defined as the combination of anti-platelet drugs, statins, beta blockers, and angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Factors for OMT and its prognostic value were analyzed in CAD patients across different subgroups. Results Out of 3176 patients, only 39.8% （n = 1265） were on OMT at discharge. Factors associated with OMT at discharge were pre-admission OMT and discharge department. All-cause mortality occurred in 6.8% （n = 217） of patients. Multivariate analyses indicated that OMT was significantly associated with reduced all-cause mortality （HR： 0.65, 95% CI： 0.45~0.95; P = 0.025）. Sub-group analyses indicate that male acute coronary syndrome （ACS） patients were more likely to receive survival benefits with OMT at discharge. The positive impact of OMT at discharge was more apparent after 24 months, regardless of revascularization therapy. Four-drug combination of OMT was superior to 3-drug combination therapy in ACS patients but not in stable patients. Conclusions OMT was asso- ciated with significant improvement in survival in patients with CAD. The positive impact of OMT was distinct in the CAD patients with different characteristics.

Optimization therapy for the treatment of chronic hepatitis B

Chronic hepatitis B (CHB) is currently medically managed with either interferon-alpha or one of the five nucleos(t)ide analogs. However, there are still a large number of CHB patients whose response to the above therapies remains less than satisfactory, and their incomplete or non-response to antiviral therapies has plagued clinicians worldwide. In recent years, a newly proposed optimization therapy has provided us with a new approach to solve this problem. The key points in this optimization therapy are to initiate antiviral therapy with an appropriate agent at the correct time point, and to adjust treatments in patients with poor early responses by adding a second agent or switching to another more potent agent. In this review, we summarize recent developments in optimization therapy for the treatment of CHB, and provide an outlook for future research in this field. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Drug delivery in ocular diseases: Barriers and strategies

The eye is a complex organ made up of diversifed cells with specifed functions. Presence of anatomical, physi-ological and physiochemical barriers make it diffcult to deliver drugs in therapeutic amounts at intended sites. To overcome these, drug delivery scientists have fol-lowed two distinct yet complimentary approaches. The frst involves using alternate delivery routes to conven-tional ones allowing for more direct access to intended target sites. Second approach involves development of novel drug delivery systems providing better perme-ability, treatability and controlled release at target site. Combination of both these approaches are being uti-lized and optimized in order to achieve optimal therapy with minimal adverse effects.

Dosimetric evaluation of CR, 3DCRT and two types of IMRT for breast cancer after conservative surgery

Objective: The purpose of this study was to compare the dose distribution and dose volume histogram (DVH) of the planning target volume (PTV) and organs at risk (OARs) among conventional radiation therapy (CR), three-dimensional conformal radiation therapy (3DCRT), two-step intensity-modulated radiation therapy (TS-IMRT) and direct machine parameter optimization intensity-modulated radiation therapy (DMPO-IMRT) after breast-conserving surgery. Methods: For each of 20 randomly chosen patients, 4 plans were designed using 4 irradiation techniques. The prescribed dose was 50 Gy/2 Gy/25 f, 95% of the planning target volume received this dose. The cumulated DVHs and 3D dose distributions of CR, 3DCRT, TS-IMRT and DMPO-IMRT plans were compared. Results: For the homogeneity indices, no statistically significant difference was observed among CR, 3DCRT, TS-IMRT and DMPO-IMRT while the difference of the conformality indices were statistically significant. With regard to the organs at risk, IMRT and 3DCRT showed a significantly fewer exposure dose to the ipsilateral lung than CR in the high-dose area while in the low-dose area, IMRT demonstrated a significant increase of exposure dose to ipsilateral lung, heart and contralateral breast compared with 3DCRT and CR. In addition, the monitor units (MUs) for DMPO-IMRT were approximately 26% more than those of TS-IMRT and the segments of the former were approximately 24% less than those of the latter. Conclusion: Compared with CR, 3DCRT and IMRT improved the homogeneity and conformity of PTV, reduced the irradiated volume of OARs in high dose area but IMRT increased the irradiated volume of OARs in low dose area. DMPO-IMRT plan has fewer delivery time but more MUs than TS-IMRT.

nitial Experience with MultiPoint Pacing Cardiac Resynchronization Therapy in China

Recently, cardiac resynchronization therapy （CRT） with multipoint left ventricular （LV） pacing in a single coronary sinus branch （MultiPointTM Pacing [MPP], St. Jude Medical, Inc., Sylmar, CA, USA） has been introduced commercially. The CRT system with MPP feature offers a new strategy for physicians to further enhance CRT in patients with heart failure. Early clinical studies have shown that MPP, compared with conventional biventricular （BiV） pacing, provides acute benefits to LV dP/dtmax, LV dyssynchrony, LV peak radial strain, and LV electrical activation, and improves CRT response at 12 months. In this report, we presented two MPP CRT cases in China with acute hemodynamic assessment under various MPP and conventional BiV pacing configurations, demonstrating that MPP can offer further benefits to patients.

Mathematical modeling and optimal control problems in brain tumor targeted drug delivery strategies

In this paper, we present a mathematical model that describes tumor-normal cells inter- action dynamics focusing on role of drugs in treatment of brain tumors. The goal is to predict distribution and necessary quantity of drugs delivered in drug-therapy by using optimal control framework. The model describes interactions of tumor and normal cells using a system of reactions^diffusion equations involving the drug concentration, tumor cells and normal tissues. The control estimates simultaneously blood perfusion rate, reabsorption rate of drug and drug dosage administered, which affect the effects of brain tumor chemotherapy. First, we develop mathematical framework which mod- els the competition between tumor and normal cells under chemotherapy constraints. Then, existence, uniqueness and regularity of solution of state equations are proved as well as stability results. Afterwards, optimal control problems are formulated in order to minimize the drug delivery and tumor cell burden in different situations. We show existence and uniqueness of optimal solution, and we derive necessary conditions for optimality. Finally, to solve numerically optimal control and optimization problems, we propose and investigate an adjoint multiple-relaxation-time lattice Boltzmann method for a general nonlinear coupled anisotropic convection-diffusion system （which includes the developed model for brain tumor targeted drug delivery system）.

Four-year clinical outcome in asymptomatic patients undergoing coronary computed tomography angiography

Background Percutaneous coronary intervention （PCI） is indicated for angina with coronary stenosis. However, PCI for asymptomatic coronary stenosis remains controversial. We prospectively followed a group of patients for four years who underwent coronary computed tomography angiography （CCTA） for major adverse cardiac events （MACE）. We hypothesized that the results of this trial would reliably reflect the natural outcome of the coronary disease. Methods Consecutive patients who underwent CCTA from June 2008 to May 2009 were selected. Those who could not be reached by telephone, had significant angina, had CT images that were not interpretable, or poor kidney and left ventricular （LV） function were excluded. The patients were divided into five groups： group A normal CCTA without stenosis, group B mild stenosis （1%-49%）, group C moderate stenosis （50%-74%）, group D severe stenosis （≥75%） and they were treated with optimal medical therapy （OMT） or PCI. The group E had PCI before the CCTA examination. The patients were then followed for MACE after different treatments. MACE included acute myocardial infarction （MI）, heart failure （HF） and death. Results The patient population consisted of 419 patients. The follow-up time was （51±5） months. The age was （60±31） years. Male made up 67.78% of the population （n=284）. A total of 51 cases of MACE occurred including 25 MI, eight HF and 18 all-cause deaths. There was no MACE in group A. Although MACE occurred in two patients in group B, they were not attributed to cardiac death. We further compared the MACE in groups C-E and no significant difference was found （P 〉0.05）. However, a difference was detected among patients with unstable angina pectods （UAP）, stable angina pectoris （SAP）, re-hospitalization, and cerebrovascular events from groups A-E （P 〈0.05）. The plaque scores were used to predict MACE. The scores progressively increased significantly with lesion severity （P 〈0.05）. Receiver operating curve （ROC） was performed to determine the sensitivity and specificity in predicting MACE. Our scores predicted MI with area of 0.76, predicted HF with area of 0.77, and predicted death with area of 0.70. Conclusions Normal and mild lesions had very few events. With increased stenosis the MACE rate increased progressively. PCI did not significantly reduce the MACE in comparison with OMT in asymptomatic patients. Furthermore, UAP, re-hospitalization, and re-PCI were sianificantlv increased in patients who were treated with PCI.