[Quality control of clinical-grade recombinant adenovirus used in gene therapy].

OBJECTIVE: To establish the quality control methods and reference standards for clinical-grade recombinant adenovirus products for human gene therapy. METHODS: The Infectivity of clinical grade recombinant adenoviral vectors is determined by a TCID(50) assay. The purity is determined by a high-performance liquid chromatography (HPLC) assay. A549 cells were used in replication competent adenovirus (RCA) assay of samples by observation of the cytopathic effect. Other quality control assays were performed in accordance with the SFDA Regulations for Biological Products. RESULTS: The recombinant adenovirus encoding human p53 gene produced at SiBiono (Lot 20010701) has the following quality attributes: viral particle concentration: 1.03 (10(12) VP/ml, infectivity titer: 5.01 (10(10) IU/ml, specific infectivity (IU/VP): 4.86%, higher than the 3.3% required by the Food and Drug Administration (FDA), USA; Purity by HPLC analysis: 98.62%, higher than the 95% purity specified by SFDA; and level of RCA: less than 1 RCA/3 (10(10) VP, meeting the standards established by SFDA. CONCLUSIONS: A whole set of quality standards of clinical-grade recombinant adenovirus vectors has been established so as to ensure the clinical safety and efficacy of recombinant adenoviral vectors for human gene therapy.

A Giant Left Main Trunk and Left Circumflex Artery-to-Right Ventricle Fistula.

Coronary artery fistula including the left trunk and left circumflex is uncommon. We present a 24-year-old male patient with a giant left main trunk and left circumflex artery to right ventricle fistula, which is diagnosed by transthoracic echocardiography and coronary computed tomography angiography. In this paper, the case report is to provide a better understanding of clinical characteristics for this disease.

Diagnostic accuracy of myocardial magnetic resonance perfusion to diagnose ischemic stenosis with fractional flow reserve as reference: systematic review and meta-analysis.

OBJECTIVES: This paper systematically analyzed the performance of magnetic resonance (MR) perfusion to diagnose coronary artery disease (CAD) with fractional flow reserve (FFR) as the reference standard. BACKGROUND: Myocardial MR perfusion has passed the stage of a research technique and has demonstrated the ability to detect functional or ischemic stenosis of coronary arteries. However, the evidence is limited to single-center studies and small sample sizes. METHODS: We searched PubMed and Embase databases for all published studies that evaluated the accuracy of MR perfusion to diagnose CAD versus FFR. We used an exact binomial rendition of the bivariate mixed-effects regression model with test type as a random-effects covariate to synthesize the available data. Based on Bayes' theorem, the post-test probability was calculated to guide MR perfusion's clinical utility. RESULTS: We identified 14 studies evaluating 1,073 arteries and 650 patients. The pooled sensitivity and specificity were 0.90 (95% confidence interval [CI]: 0.86 to 0.93) and 0.87 (95% CI: 0.82 to 0.90) at the patient level and 0.89 (95% CI: 0.83 to 0.92) and 0.86 (95% CI: 0.77 to 0.92) at the artery and territory levels, respectively. The area under the summary receiver-operating characteristic at the patient level was 0.95 (95% CI: 0.92 to 0.96) and 0.93 (95% CI: 0.91 to 0.95) at the artery and territory levels, respectively. MR perfusion could increase the post-test probability of CAD >80% in patients with a pre-test probability of >37% and can decrease post-test probability of CAD <20% with a pre-test probability of <72%. CONCLUSIONS: With FFR as the reference standard, the diagnostic ability of MR perfusion to detect ischemic CAD is high.

The diagnostic performance of coronary artery angiography with 64-MSCT and post 64-MSCT: systematic review and meta-analysis.

PURPOSE: To comprehensively investigate the diagnostic performance of coronary artery angiography with 64-MDCT and post 64-MDCT. MATERIALS AND METHODS: PubMed was searched for all published studies that evaluated coronary arteries with 64-MDCT and post 64-MDCT. The clinical diagnostic role was evaluated by applying the likelihood ratios (LRs) to calculate the post-test probability based on Bayes' theorem. RESULTS: 91 studies that met our inclusion criteria were ultimately included in the analysis. The pooled positive and negative LRs at patient level were 8.91 (95% CI, 7.53, 10.54) and 0.02 (CI, 0.01, 0.03), respectively. For studies that did not claim that non-evaluable segments were included, the pooled positive and negative LRs were 11.16 (CI, 8.90, 14.00) and 0.01 (CI, 0.01, 0.03), respectively. For studies including uninterruptable results, the diagnostic performance decreased, with the pooled positive LR 7.40 (CI, 6.00, 9.13) and negative LR 0.02 (CI, 0.01, 0.03). The areas under the summary ROC curve were 0.98 (CI, 0.97 to 0.99) for 64-MDCT and 0.96 (CI, 0.94 to 0.98) for post 64-MDCT, respectively. For references explicitly stating that the non-assessable segments were included during analysis, a post-test probability of negative results >95% and a positive post-test probability <95% could be obtained for patients with a pre-test probability of <73% for coronary artery disease (CAD). On the other hand, when the pre-test probability of CAD was >73%, the diagnostic role was reversed, with a positive post-test probability of CAD >95% and a negative post-test probability of CAD <95%. CONCLUSION: The diagnostic performance of post 64-MDCT does not increase as compared with 64-MDCT. CTA, overall, is a test of exclusion for patients with a pre-test probability of CAD<73%, while for patients with a pre-test probability of CAD>73%, CTA is a test used to confirm the presence of CAD.

SPECT myocardial perfusion versus fractional flow reserve for evaluation of functional ischemia: a meta analysis.

PURPOSE: The present meta-analysis illustrates the accuracy of myocardial perfusion SPECT (MPS) to diagnose functional stenotic coronary artery disease (CAD) with fractional flow reserve (FFR) as standard reference. METHODS: All investigators screened and selected studies that compared MPS with FFR in symptomatic patients with suspected CAD. Patients and study characteristics were independently extracted by two investigators; differences were resolved by consensus. RESULTS: 13 articles, including 1,017 patients, 699 vessels were included in the study. No significant publication bias was detected (P=0.65). At the patient level, the summary sensitivity and specificity were 77% (95% confidence interval [CI], 70-83%) and 77% (95%CI, 67-84%) for MPS. Vessel-level pooled sensitivity was 66% (95%CI, 57-74%) and specificity was 81% (95%CI, 70-89%). The overall diagnostic performance of MPS was moderate. [The area under the summary receiver operating characteristic (sROC) curve was 0.83]. No study influenced the pooled results larger than 0.03. CONCLUSIONS: The accuracy between FFR and MPS SPECT was moderate.

Diagnostic accuracy of dual-source CT coronary angiography in patients with atrial fibrillation: meta analysis.

RATIONALE AND OBJECTIVE: To synthesize the available data to underscore the diagnostic accuracy of dual-source CT (DSCT) coronary angiography in patients with atrial fibrillation (AF). MATERIALS AND METHODS: We searched in the electronic databases of PubMed for all published studies that examined patients with AF using DSCT. We used an exact binomial rendition of the bivariate mixed-effects regression model to synthesize the diagnostic data. RESULTS: The positive and negative likelihood ratios (LRs) at the patient level were 6.0 (CI, 3.6-10.1) and 0.03(CI, 0.004-0.2), respectively. The negative predictive values higher than 90% were available for a CAD prevalence <78%. The pooled vessel- and segment-level estimates showed higher positive and negative LRs than the patient-level estimates (15.3 [CI, 9.8-23.9] and 0.1 [CI, 0.07-0.3]; 25.1 [CI, 10.8-58.5] and 0.2 [CI, 0.2-0.3], respectively). No statistically significant heterogeneity between studies and publication bias were found at the patient level estimate. A sensitivity analysis showed that no study influenced the pooled results larger than 0.02. CONCLUSIONS: Cardiac angiography with DSCT can be applied as an imaging test for ruling out CAD in patient with AF. However, DSCT angiography may be not an effective tool for risk stratification for the high negative LR at the artery and segment levels.

Risk factors for non-calcified plaques in asymptomatic population.

RATIONALE AND OBJECTIVES: The aims of this study were to assess the prevalence of noncalcified coronary plaques in asymptomatic patients and to investigate the risk factors. MATERIALS AND METHODS: In this study, 584 patients were recruited prospectively. Patients were classified as having low, intermediate, or high pretest likelihoods of coronary artery disease according to the Morise score. Coronary computed tomographic angiography was performed in all patients using a 320-detector row dynamic-volume computed tomographic scanner. Imaging reconstruction was performed, and the postprocessed data were analyzed. Logistic regression analysis was used to evaluate the relationship between risk factors and the presence of noncalcified plaque. RESULTS: Coronary computed tomographic angiography revealed noncalcified plaques in 38.3% of all patients (224 of 584). The prevalence of noncalcified plaques was significantly higher in patients with calcium scores > 0 (P < .001). Significant differences were found between the degrees of luminal stenosis among patients with low, intermediate, and high pretest likelihoods of coronary artery disease (P = .001), while the prevalence of noncalcified plaques did not differ with the Morise score (P = .08). Noncalcified plaque was associated with hypercholesterolemia (P = .02) and diabetes mellitus (P = .002). Age (P = .47), gender (P = .58), estrogen status (P = .55), smoking (P = .22), hypertension (P = .27), and family history (P = .09) did not differ between patients with and those without noncalcified plaques. CONCLUSIONS: Hypercholesterolemia and diabetes mellitus are high risk factors for the prevalence of noncalcified plaques for asymptomatic patients.

Evaluation of anterior ethmoidal artery by 320-slice CT angiography with comparison to three-dimensional spin digital subtraction angiography: initial experiences.

OBJECTIVE: To explore the usefulness of 320-slice CT angiography (CTA) for evaluating the course of the anterior ethmoidal artery (AEA) and its relationship with adjacent structures by using three-dimensional (3D) spin digital subtraction angiography (DSA) as standard reference. MATERIALS AND METHODS: From December 2008 to December 2010, 32 patients with cerebrovascular disease, who underwent both cranial 3D spin DSA and 320-slice CTA within a 30 day period from each other, were retrospectively reviewed. AEA course in ethmoid was analyzed in DSA and CTA. In addition, adjacent bony landmarks (bony notch in medial orbital wall, anterior ethmoidal canal, and anterior ethmoidal sulcus) were evaluated with CTA using the MPR technique oriented along the axial, coronal and oblique coronal planes in all patients. The dose length product (DLP) for CTA and the dose-area product (DAP) for 3D spin DSA were recorded. Effective dose (ED) was calculated. RESULTS: The entire course of the AEA was seen in all 32 cases (100%) with 3D spine DSA and in 29 of 32 cases (90.1%) with 320-slice CTA, with no significant difference (p = 0.24). In three cases where AEA was not visualized on 320-slice CTA, two were due to the dominant posterior ethmoidal artery, while the remaining case was due to diminutive AEA. On MPR images of 320-slice CT, a bony notch in the orbital medial walls was detected in all cases (100%, 64 of 64); anterior ethmoidal canal was seen in 28 of 64 cases (43.8%), and the anterior ethmoidal sulcus was seen in 63 of 64 cases (98.4%). The mean effective dose in CTA was 0.6 ± 0.25 mSv, which was significantly lower than for 3D spin DSA (1.3 ± 0.01 mSv) (p < 0.001). CONCLUSION: 320-slice CTA has a similar detection rate for AEA to that of 3D spin DSA; however, it is noninvasive, and may be preferentially used for the evaluation of AEA and its adjacent bony variations and pathologic changes in preoperative patients with paranasal sinus diseases.

Transthoracic Doppler echocardiography to predict optimal tube pulsing window for coronary artery CT angiography.

RATIONALE AND OBJECTIVE: To evaluate the feasibility of transthoracic Doppler echocardiography to determine the optimal pulsing windows for CT coronary angiography to narrow the pulsing windows further, especially in higher heart rate. MATERIALS AND METHODS: Doppler was performed on 135 patients before CT scanning. For Doppler, the intervals with minimal motion were evaluated during both systole and diastole integrating electrocardiogram (ECG) intervals. For CT scanning, the retrospective ECG-gating was applied and the optimal reconstruction intervals were determined. The accuracy of Doppler analysis to predict the optimal reconstruction intervals was tested. The predicted length of pulsing windows was compared between Doppler analysis and traditional prospective ECG-gating protocol (heart rate≦65 bpm, 60-76%; 66-79 bpm, 30-77%; ≧80 bpm, 31-47%). RESULTS: According to Doppler analysis, the mean length of intervals with minimal motion in systole was 106.4±39.2 ms and 125.2±92.0 ms in diastole. When the intervals with minimal motion during diastole>90 ms, the optimal reconstruction intervals were located at diastole; otherwise, at systole (P<0.001). The optimal reconstruction intervals in 93.8% (132/135) patients could be predicted accurately by Doppler analysis. If the optimal reconstruction intervals predicted by Doppler were applied as the exposure windows, the mean length of pulsing windows should has been 105.2±69.4 ms (range: 26.9-510.3 ms), which was significantly shorter than that of traditional prospective ECG-gating protocol (232.0±120.2 ms, range: 93.2-427.3 ms, P<0.001). CONCLUSION: Doppler can help detecting the optimal pulsing windows accurately. Prospective ECG-gating incorporating Doppler analysis may narrow pulsing windows significantly while maintaining image quality.