Chemotherapy-Related Cardiac Dysfunction:Quantitative Cardiac Magnetic Resonance Image Parameters and Their Prognostic Implications

Objective@#To quantitatively analyze the cardiac magnetic resonance imaging (CMR) characteristics of chemotherapy-related cardiac dysfunction (CTRCD) and explore their prognostic value for major adverse cardiovascular events (MACE). @*Materials and Methods@#A total of 145 patients (male:female = 76:69, mean age = 63.0 years) with cancer and heart failure who underwent CMR between January 2015 and January 2021 were included. CMR was performed using a 3T scanner (Siemens). Biventricular functions, native T1 T2, extracellular volume fraction (ECV) values, and late gadolinium enhancement (LGE) of the left ventricle (LV) were compared between those with and without CTRCD. These were compared between patients with mild-to-moderate CTRCD and those with severe CTRCD. Cox proportional hazard regression analysis was used to evaluate the association between the CMR parameters and MACE occurrence during follow-up in the CTRCD patients. @*Results@#Among 145 patients, 61 had CTRCD and 84 did not have CTRCD. Native T1, ECV, and T2 were significantly higher in the CTRCD group (1336.9 ms, 32.5%, and 44.7 ms, respectively) than those in the non-CTRCD group (1303.4 ms, 30.5%, and 42.0 ms, respectively; P = 0.013, 0.010, and < 0.001, respectively). They were not significantly different between patients with mild-to-moderate and severe CTRCD. Indexed LV mass was significantly smaller in the CTRCD group (65.0 g/m2 vs. 78.9 g/m2 ; P < 0.001). According to the multivariable Cox regression analysis, T2 (hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 1.01–1.27; P = 0.028) and quantified LGE (HR: 1.07, 95% CI: 1.01–1.13; P = 0.021) were independently associated with MACE in the CTRCD patients. @*Conclusion@#Quantitative parameters from CMR have the potential to evaluate myocardial changes in CTRCD. Increased T2 with reduced LV mass was demonstrated in CTRCD patients even before the development of severe cardiac dysfunction. T2 and quantified LGE may be independent prognostic factors for MACE in patients with CTRCD.

Protective efficacy of attenuated Salmonella Typhimurium strain expressing BLS, Omp19, PrpA, or SOD of Brucella abortus in goats

Background@#Attenuated Salmonella strain can be used as a vector to transport immunogens to the host antigen-binding sites. @*Objectives@#The study aimed to determine the protective efficacy of attenuated Salmonellastrain expressing highly conserved Brucella immunogens in goats. @*Methods@#Goats were vaccinated with Salmonella vector expressing individually lipoprotein outer-membrane protein 19 (Omp19), Brucella lumazine synthase (BLS), proline racemase subunit A (PrpA), Cu/Zn superoxide dismutase (SOD) at 5 × 10 9 CFU/mL and challenge of all groups was done at 6 weeks after vaccination. @*Results@#Among these vaccines inoculated at 5 × 10 9 CFU/mL in 1 mL, Omp19 or SOD showed significantly higher serum immunoglobulin G titers at (2, 4, and 6) weeks post-vaccination, compared to the vector control. Interferon-γ production in response to individual antigens was significantly higher in SOD, Omp19, PrpA, and BLS individual groups, compared to that in the vector control (all p < 0.05). Brucella colonization rate at 8 weeks post-challenge showed that most vaccine-treated groups exhibited significantly increased protection by demonstrating reduced numbers of Brucella in tissues collected from vaccinated groups. Realtime polymerase chain reaction revealed that Brucella antigen expression levels were reduced in the spleen, kidney, and parotid lymph node of vaccinated goats, compared to the nonvaccinated goats. Besides, treatment with vaccine expressing individual antigens ameliorated brucellosis-related histopathological lesions. @*Conclusions@#These results delineated that BLS, Omp19, PrpA, and SOD proteins achieved a definite level of protection, indicating that Salmonella Typhimurium successfully delivered Brucella antigens, and that individual vaccines could differentially elicit an antigen-specific immune response.

Sodium/glucose Co-Transporter 2 Inhibitor, Empagliflozin, Alleviated Transient Expression of SGLT2 after Myocardial Infarction

Background and Objectives@#Large clinical studies of sodium/glucose cotransporter 2 (SGLT2) inhibitors have shown a significant beneficial effect on heart failure-associated hospitalization and cardiovascular events. As SGLT2 is known to be absent in heart cells, improved cardiovascular outcomes are thought to be accounted for by the indirect effects of the drug. We sought to confirm whether such benefits were mediated through SGLT2 expressed in the heart using myocardial infarction (MI) model. @*Methods@#Mice pre-treated with empagliflozin (EMPA), an SGLT2 inhibitor, showed a significantly reduced infarct size compared with the vehicle group three days post-MI.Interestingly, we confirmed SGLT2 localized in the infarct zone. The sequential changes of SGLT2 expression after MI were also evaluated. @*Results@#One day after MI, SGLT2 transiently appeared in the ischemic areas in the vehicle group and increased until 72 hours. The appearance of SGLT2 was delayed and less in amount compared with the vehicle group. Additionally, there was a significant difference in metabolites, including glucose and amino acids in the 1 H nuclear magnetic resonance analysis between groups. @*Conclusions@#Our work demonstrates that SGLT2 is transiently expressed in heart tissue early after MI and EMPA may directly operate on SGLT2 to facilitate metabolic substrates shifts.

Regional Amyloid Burden Differences Evaluated Using Quantitative Cardiac MRI in Patients with Cardiac Amyloidosis

Objective@#This study aimed to investigate the regional amyloid burden and myocardial deformation using T1 mapping and strain values in patients with cardiac amyloidosis (CA) according to late gadolinium enhancement (LGE) patterns. @*Materials and Methods@#Forty patients with CA were divided into 2 groups per LGE pattern, and 15 healthy subjects were enrolled. Global and regional native T1 and T2 mapping, extracellular volume (ECV), and cardiac magnetic resonance (CMR)-feature tracking strain values were compared in an intergroup and interregional manner. @*Results@#Of the patients with CA, 32 had diffuse global LGE (group 2), and 8 had focal patchy or no LGE (group 1). Global native T1, T2, and ECV were significantly higher in groups 1 and 2 than in the control group (native T1: 1384.4 ms vs. 1466.8 ms vs. 1230.5 ms; T2: 53.8 ms vs. 54.2 ms vs. 48.9 ms; and ECV: 36.9% vs. 51.4% vs. 26.0%, respectively; all, p < 0.001). Basal ECV (53.7%) was significantly higher than the mid and apical ECVs (50.1% and 50.0%, respectively; p < 0.001) in group 2. Basal and mid peak radial strains (PRSs) and peak circumferential strains (PCSs) were significantly lower than the apical PRS and PCS, respectively (PRS, 15.6% vs. 16.7% vs. 26.9%; and PCS, -9.7% vs. -10.9% vs. -15.0%; all, p < 0.001). Basal ECV and basal strain (2-dimensional PRS) in group 2 showed a significant negative correlation (r = -0.623, p < 0.001). Group 1 showed no regional ECV differences (basal, 37.0%; mid, 35.9%; and apical, 38.3%; p = 0.184). @*Conclusion@#Quantitative T1 mapping parameters such as native T1 and ECV may help diagnose early CA. ECV, in particular, can reflect regional differences in the amyloid deposition in patients with advanced CA, and increased basal ECV is related to decreased basal strain. Therefore, quantitative CMR parameters may help diagnose CA and determine its severity in patients with or without LGE.

Dual-Energy CT for Pulmonary Embolism: Current and Evolving Clinical Applications

Pulmonary embolism (PE) is a potentially fatal disease if the diagnosis or treatment is delayed. Currently, multidetector computed tomography (MDCT) is considered the standard imaging method for diagnosing PE. Dual-energy CT (DECT) has the advantages of MDCT and can provide functional information for patients with PE. The aim of this review is to present the potential clinical applications of DECT in PE, focusing on the diagnosis and risk stratification of PE.

Protective efficacy of attenuated Salmonella Typhimurium strain expressing BLS, Omp19, PrpA, or SOD of Brucella abortus in goats

Background@#Attenuated Salmonella strain can be used as a vector to transport immunogens to the host antigen-binding sites. @*Objectives@#The study aimed to determine the protective efficacy of attenuated Salmonellastrain expressing highly conserved Brucella immunogens in goats. @*Methods@#Goats were vaccinated with Salmonella vector expressing individually lipoprotein outer-membrane protein 19 (Omp19), Brucella lumazine synthase (BLS), proline racemase subunit A (PrpA), Cu/Zn superoxide dismutase (SOD) at 5 × 10 9 CFU/mL and challenge of all groups was done at 6 weeks after vaccination. @*Results@#Among these vaccines inoculated at 5 × 10 9 CFU/mL in 1 mL, Omp19 or SOD showed significantly higher serum immunoglobulin G titers at (2, 4, and 6) weeks post-vaccination, compared to the vector control. Interferon-γ production in response to individual antigens was significantly higher in SOD, Omp19, PrpA, and BLS individual groups, compared to that in the vector control (all p < 0.05). Brucella colonization rate at 8 weeks post-challenge showed that most vaccine-treated groups exhibited significantly increased protection by demonstrating reduced numbers of Brucella in tissues collected from vaccinated groups. Realtime polymerase chain reaction revealed that Brucella antigen expression levels were reduced in the spleen, kidney, and parotid lymph node of vaccinated goats, compared to the nonvaccinated goats. Besides, treatment with vaccine expressing individual antigens ameliorated brucellosis-related histopathological lesions. @*Conclusions@#These results delineated that BLS, Omp19, PrpA, and SOD proteins achieved a definite level of protection, indicating that Salmonella Typhimurium successfully delivered Brucella antigens, and that individual vaccines could differentially elicit an antigen-specific immune response.

Sodium/glucose Co-Transporter 2 Inhibitor, Empagliflozin, Alleviated Transient Expression of SGLT2 after Myocardial Infarction

Background and Objectives@#Large clinical studies of sodium/glucose cotransporter 2 (SGLT2) inhibitors have shown a significant beneficial effect on heart failure-associated hospitalization and cardiovascular events. As SGLT2 is known to be absent in heart cells, improved cardiovascular outcomes are thought to be accounted for by the indirect effects of the drug. We sought to confirm whether such benefits were mediated through SGLT2 expressed in the heart using myocardial infarction (MI) model. @*Methods@#Mice pre-treated with empagliflozin (EMPA), an SGLT2 inhibitor, showed a significantly reduced infarct size compared with the vehicle group three days post-MI.Interestingly, we confirmed SGLT2 localized in the infarct zone. The sequential changes of SGLT2 expression after MI were also evaluated. @*Results@#One day after MI, SGLT2 transiently appeared in the ischemic areas in the vehicle group and increased until 72 hours. The appearance of SGLT2 was delayed and less in amount compared with the vehicle group. Additionally, there was a significant difference in metabolites, including glucose and amino acids in the 1 H nuclear magnetic resonance analysis between groups. @*Conclusions@#Our work demonstrates that SGLT2 is transiently expressed in heart tissue early after MI and EMPA may directly operate on SGLT2 to facilitate metabolic substrates shifts.

Regional Amyloid Burden Differences Evaluated Using Quantitative Cardiac MRI in Patients with Cardiac Amyloidosis

Objective@#This study aimed to investigate the regional amyloid burden and myocardial deformation using T1 mapping and strain values in patients with cardiac amyloidosis (CA) according to late gadolinium enhancement (LGE) patterns. @*Materials and Methods@#Forty patients with CA were divided into 2 groups per LGE pattern, and 15 healthy subjects were enrolled. Global and regional native T1 and T2 mapping, extracellular volume (ECV), and cardiac magnetic resonance (CMR)-feature tracking strain values were compared in an intergroup and interregional manner. @*Results@#Of the patients with CA, 32 had diffuse global LGE (group 2), and 8 had focal patchy or no LGE (group 1). Global native T1, T2, and ECV were significantly higher in groups 1 and 2 than in the control group (native T1: 1384.4 ms vs. 1466.8 ms vs. 1230.5 ms; T2: 53.8 ms vs. 54.2 ms vs. 48.9 ms; and ECV: 36.9% vs. 51.4% vs. 26.0%, respectively; all, p < 0.001). Basal ECV (53.7%) was significantly higher than the mid and apical ECVs (50.1% and 50.0%, respectively; p < 0.001) in group 2. Basal and mid peak radial strains (PRSs) and peak circumferential strains (PCSs) were significantly lower than the apical PRS and PCS, respectively (PRS, 15.6% vs. 16.7% vs. 26.9%; and PCS, -9.7% vs. -10.9% vs. -15.0%; all, p < 0.001). Basal ECV and basal strain (2-dimensional PRS) in group 2 showed a significant negative correlation (r = -0.623, p < 0.001). Group 1 showed no regional ECV differences (basal, 37.0%; mid, 35.9%; and apical, 38.3%; p = 0.184). @*Conclusion@#Quantitative T1 mapping parameters such as native T1 and ECV may help diagnose early CA. ECV, in particular, can reflect regional differences in the amyloid deposition in patients with advanced CA, and increased basal ECV is related to decreased basal strain. Therefore, quantitative CMR parameters may help diagnose CA and determine its severity in patients with or without LGE.

Dual-Energy CT for Pulmonary Embolism: Current and Evolving Clinical Applications

Pulmonary embolism (PE) is a potentially fatal disease if the diagnosis or treatment is delayed. Currently, multidetector computed tomography (MDCT) is considered the standard imaging method for diagnosing PE. Dual-energy CT (DECT) has the advantages of MDCT and can provide functional information for patients with PE. The aim of this review is to present the potential clinical applications of DECT in PE, focusing on the diagnosis and risk stratification of PE.

Prognostic Value of Dual-Energy CT-Based IodineQuantification versus Conventional CT in AcutePulmonary Embolism: A Propensity-Match Analysis

Objective@#The present study aimed to investigate whether quantitative dual-energy computed tomography (DECT) parametersoffer an incremental risk stratification benefit over the CT ventricular diameter ratio in patients with acute pulmonary embolism(PE) by using propensity score analysis. @*Materials and Methods@#This study was conducted on 480 patients with acute PE who underwent CT pulmonary angiography(CTPA) or DECT pulmonary angiography (DE CT-PA). This propensity-matched study population included 240 patients with acutePE each in the CTPA and DECT groups. Altogether, 260 (54.1%) patients were men, and the mean age was 64.9 years (64.9 ±13.5 years). The primary endpoint was all-cause death within 30 days. The Cox proportional hazards regression model was usedto identify associations between CT parameters and outcomes and to identify potential predictors. Concordance (C) statisticswere used to compare the prognoses between the two groups. @*Results@#In both CTPA and DECT groups, right to left ventricle diameter ratio ≥ 1 was associated with an increased risk of allcausedeath within 30 days (hazard ratio: 3.707, p< 0.001 and 5.573, p< 0.001, respectively). However, C-statisticsshowed no statistically significant difference between the CTPA and DECT groups for predicting death within 30 days(C-statistics: 0.759 vs. 0.819, p= 0.117). @*Conclusion@#Quantitative measurement of lung perfusion defect volume by DECT had no added benefit over CT ventriculardiameter ratio for predicting all-cause death within 30 days.

Analysis of Complications of Percutaneous Transthoracic Needle Biopsy Using CT-Guidance Modalities In a Multicenter Cohort of 10568 Biopsies

OBJECTIVE: To analyze the complications of percutaneous transthoracic needle biopsy using CT-based imaging modalities for needle guidance in comparison with fluoroscopy in a large retrospective cohort. MATERIALS AND METHODS: This study was approved by multiple Institutional Review Boards and the requirement for informed consent was waived. We retrospectively included 10568 biopsies from eight referral hospitals from 2010 through 2014. In univariate and multivariate logistic analyses, 3 CT-based guidance modalities (CT, CT fluoroscopy, and cone-beam CT) were compared with fluoroscopy in terms of the risk of pneumothorax, pneumothorax requiring chest tube insertion, and hemoptysis, with adjustment for other risk factors. RESULTS: Pneumothorax occurred in 2298 of the 10568 biopsies (21.7%). Tube insertion was required after 316 biopsies (3.0%), and hemoptysis occurred in 550 cases (5.2%). In the multivariate analysis, pneumothorax was more frequently detected with CT {odds ratio (OR), 2.752 (95% confidence interval [CI], 2.325–3.258), p < 0.001}, CT fluoroscopy (OR, 1.440 [95% CI, 1.176–1.762], p < 0.001), and cone-beam CT (OR, 2.906 [95% CI, 2.235–3.779], p < 0.001), but no significant relationship was found for pneumothorax requiring chest tube insertion (p = 0.497, p = 0.222, and p = 0.216, respectively). The incidence of hemoptysis was significantly lower under CT (OR, 0.348 [95% CI, 0.247–0.491], p < 0.001), CT fluoroscopy (OR, 0.594 [95% CI, 0.419–0.843], p = 0.004), and cone-beam CT (OR, 0.479 [95% CI, 0.317–0.724], p < 0.001) guidance. CONCLUSION: Hemoptysis occurred less frequently with CT-based guidance modalities in comparison with fluoroscopy. Although pneumothorax requiring chest tube insertion showed a similar incidence, pneumothorax was more frequently detected using CT-based guidance modalities.

Erratum: Analysis of Complications of Percutaneous Transthoracic Needle Biopsy Using CT-Guidance Modalities In a Multicenter Cohort of 10568 Biopsies

On page 323, the grant number was incorrectly numbered as HI15C1234. The correct number is HI15C3390.

Planting Seeds into the Lung: Image-Guided Percutaneous Localization to Guide Minimally Invasive Thoracic Surgery

Image-guided localization materials are constantly evolving, providing options for the localization of small pulmonary nodules to guide minimally invasive thoracic surgery. Several preoperative methods have been developed to localize small pulmonary lesions prior to video-assisted thoracic surgery. These localization techniques can be categorized into 4 groups according to the materials used: localization with metallic materials (hook-wire, microcoil, or spiral coil), localization with dye (methylene blue or indigo carmine), localization with contrast agents (lipiodol, barium, or iodine contrast agents), and radiotracers (technetium-99m). However, the optimal localization method has not yet been established. In this review article, we discuss the various localization techniques and the advantages and disadvantages of localization techniques as well as the available safety and efficacy data on these techniques.

Diagnostic Accuracy of Percutaneous Transthoracic Needle Lung Biopsies: A Multicenter Study

OBJECTIVE: To measure the diagnostic accuracy of percutaneous transthoracic needle lung biopsies (PTNBs) on the basis of the intention-to-diagnose principle and identify risk factors for diagnostic failure of PTNBs in a multi-institutional setting. MATERIALS AND METHODS: A total of 9384 initial PTNBs performed in 9239 patients (mean patient age, 65 years [range, 20–99 years]) from January 2010 to December 2014 were included. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PTNBs for diagnosis of malignancy were measured. The proportion of diagnostic failures was measured, and their risk factors were identified. RESULTS: The overall accuracy, sensitivity, specificity, PPV, and NPV were 91.1% (95% confidence interval [CI], 90.6–91.7%), 92.5% (95% CI, 91.9–93.1%), 86.5% (95% CI, 85.0–87.9%), 99.2% (95% CI, 99.0–99.4%), and 84.3% (95% CI, 82.7–85.8%), respectively. The proportion of diagnostic failures was 8.9% (831 of 9384; 95% CI, 8.3–9.4%). The independent risk factors for diagnostic failures were lesions ≤ 1 cm in size (adjusted odds ratio [AOR], 1.86; 95% CI, 1.23–2.81), lesion size 1.1–2 cm (1.75; 1.45–2.11), subsolid lesions (1.81; 1.32–2.49), use of fine needle aspiration only (2.43; 1.80–3.28), final diagnosis of benign lesions (2.18; 1.84–2.58), and final diagnosis of lymphomas (10.66; 6.21–18.30). Use of cone-beam CT (AOR, 0.31; 95% CI, 0.13–0.75) and conventional CT-guidance (0.55; 0.32–0.94) reduced diagnostic failures. CONCLUSION: The accuracy of PTNB for diagnosis of malignancy was fairly high in our large-scale multi-institutional cohort. The identified risk factors for diagnostic failure may help reduce diagnostic failure and interpret the biopsy results.

A Salmonella Typhi ghost induced by the E gene of phage φX174 stimulates dendritic cells and efficiently activates the adaptive immune response

Previously, we genetically engineered a Salmonella Typhi bacterial ghost (STG) as a novel inactivated vaccine candidate against typhoid fever. The underlying mechanism employed by the ghost in stimulating the adaptive immune response remains to be investigated. In this study, we aimed to evaluate the immunostimulatory effect of STG on mouse bone marrow-derived dendritic cells (BMDCs) and its activation of the adaptive immune response in vitro. Immature BMDCs were stimulated with STG, which efficiently stimulated maturation events in BMDCs, as indicated by upregulated expressions of CD40, CD80, and major histocompatibility complex class II molecules on CD11⁺ BMDCs. Immature BMDCs responded to STG stimulation by significantly increasing the expression of interleukin (IL)-6, which might indicate the induction of dendritic cell maturation in vivo (p < 0.05). In addition, ghost-stimulated murine BMDCs showed significant expressions of interferon gamma and IL-4, which can drive the development of Th1 and Th2 cells, respectively, in co-cultured CD4⁺ T cells in vitro. These results suggest that STG can effectively stimulate maturation of BMDCs and facilitate subsequent immune responses via potent immunomodulatory cytokine responses.

Vaccination of goats with a combination Salmonella vector expressing four Brucella antigens (BLS, PrpA, Omp19, and SOD) confers protection against Brucella abortus infection

Salmonella is an intracellular pathogen with a cellular infection mechanism similar to that of Brucella, making it a suitable choice for use in an anti-Brucella immune boost system. This study explores the efficacy of a Salmonella Typhimurium delivery-based combination vaccine for four heterologous Brucella antigens (Brucella lumazine synthase, proline racemase subunit A, outer-membrane protein 19, and Cu/Zn superoxide dismutase) targeting brucellosis in goats. We inoculated the attenuated Salmonella delivery-based vaccine combination subcutaneously at two different inoculation levels; 5 × 10⁹ colony-forming unit (CFU)/mL (Group B) and 5 × 10¹⁰ CFU/mL (Group C) and challenged the inoculations with virulent Brucella abortus at 6 weeks post-immunization. Serum immunoglobulin G titers against individual antigens in Salmonella immunized goats (Group C) were significantly higher than those of the non-immunized goats (Group A) at 3 and 6 weeks after vaccination. Upon antigenic stimulation, interferon-γ from peripheral blood mononuclear cells was significantly elevated in Groups B and C compared to that in Group A. The immunized goats had a significantly higher level of protection as demonstrated by the low bacterial loads in most tissues from the goats challenged with B. abortus. Relative real-time polymerase chain reaction results revealed that the expression of Brucella antigens was lower in spleen, kidney, and lung of immunized goats than of non-immunized animals. Also, treatment with our combination vaccine ameliorated histopathological lesions induced by the Brucella infection. Overall, the Salmonella Typhimurium delivery-based combination vaccine was effective in delivering immunogenic Brucella proteins, making it potentially useful in protecting livestock from brucellosis.

Myocardial T1 and T2 Mapping: Techniques and Clinical Applications

Cardiac magnetic resonance (CMR) imaging is widely used in various medical fields related to cardiovascular diseases. Rapid technological innovations in magnetic resonance imaging in recent times have resulted in the development of new techniques for CMR imaging. T1 and T2 image mapping sequences enable the direct quantification of T1, T2, and extracellular volume fraction (ECV) values of the myocardium, leading to the progressive integration of these sequences into routine CMR settings. Currently, T1, T2, and ECV values are being recognized as not only robust biomarkers for diagnosis of cardiomyopathies, but also predictive factors for treatment monitoring and prognosis. In this study, we have reviewed various T1 and T2 mapping sequence techniques and their clinical applications.

Predictors of False-Negative Results from Percutaneous Transthoracic Fine-Needle Aspiration Biopsy: An Observational Study from a Retrospective Cohort

PURPOSE: We investigated factors predictive of false-negative pulmonary lesions with nonspecific benign cytology results on percutaneous transthoracic fine-needle aspiration biopsy (FNAB). MATERIALS AND METHODS: We included 222 pulmonary lesions that had a nonspecific benign result from percutaneous transthoracic FNAB between March 2005 and December 2012, and were confirmed by subsequent pathologic results or adequate clinical follow up over at least 2 years. Clinical, imaging, and biopsy procedure-related findings were compared between lesions with a final diagnosis of malignancy (false-negative) and lesions with a benign diagnosis (true-negative). Multivariate logistic regression analysis was performed to identify significant predictors of false-negatives. RESULTS: Of 222 lesions, 115 lesions were proved to be false-negatives, and 107 were true-negatives. Compared with the true-negatives, false-negative lesions showed significantly older age (p=0.037), higher maximum standardized uptake value (SUVmax) on positron emission tomography (p=0.001), larger lesion size (p=0.007), and lesion characteristics of a subsolid nodule (p=0.007). On multivariate logistic regression analysis, SUVmax, lesion size, and lesion characteristics were significant predictors of false-negative results. CONCLUSION: Among the clinical, radiologic, and procedure-related factors analyzed, high SUVmax, large lesion size, and subsolid lesions were useful for predicting malignancy in pulmonary lesions with nonspecific benign cytology results on FNAB.

COMP-Ang1 Potentiates EPC Treatment of Ischemic Brain Injury by Enhancing Angiogenesis Through Activating AKT-mTOR Pathway and Promoting Vascular Migration Through Activating Tie2-FAK Pathway

Successful recovery from brain ischemia is limited due to poor vascularization surrounding the ischemic zone. Cell therapy with strong angiogenic factors could be an effective strategy to rescue the ischemic brain. We investigated whether cartilage oligomeric matrix protein (COMP)-Ang1, a soluble, stable and potent Ang1 variant, enhances the angiogenesis of human cord blood derived endothelial progenitor cells (hCB-EPCs) for rescuing brain from ischemic injury. COMP-Ang1 markedly improved the tube formation of capillaries by EPCs and incorporation of EPCs into tube formation with human umbilical vein endothelial cells (HUVECs) upon incubation on matrigel in vitro. COMP-Ang1 stimulated the migration of EPCs more than HUVECs in a scratch wound migration assay. The transplanted EPCs and COMP-Ang1 were incorporated into the blood vessels and decreased the infarct volume in the rat ischemic brain. Molecular studies revealed that COMP-Ang1 induced an interaction between Tie2 and FAK, but AKT was separated from the Tie2-FAK-AKT complex in the EPC plasma membrane. Tie2-FAK increased pp38, pSAPK/JNK, and pERK-mediated MAPK activation and interacted with integrins alphanubeta3, alpha4, beta1, finally leading to migration of EPCs. AKT recruited mTOR, SDF-1, and HIF-1alpha to induce angiogenesis. Taken together, it is concluded that COMP-Ang1 potentiates the angiogenesis of EPCs and enhances the vascular morphogenesis indicating that combination of EPCs with COMP-Ang1 may be a potentially effective regimen for ischemic brain injury salvage therapy.

Measurement of Opening and Closing Angles of Aortic Valve Prostheses In Vivo Using Dual-Source Computed Tomography: Comparison with Those of Manufacturers' in 10 Different Types

OBJECTIVE: The aims of this study were to compare opening and closing angles of normally functioning mechanical aortic valves measured on dual-source computed tomography (CT) with the manufacturers' values and to compare CT-measured opening angles according to valve function. MATERIALS AND METHODS: A total of 140 patients with 10 different types of mechanical aortic valves, who underwent dual-source cardiac CT, were included. Opening and closing angles were measured on CT images. Agreement between angles in normally functioning valves and the manufacturer values was assessed using the interclass coefficient and the Bland-Altman method. CT-measured opening angles were compared between normal functioning valves and suspected dysfunctioning valves. RESULTS: The CT-measured opening angles of normally functioning valves and manufacturers' values showed excellent agreement for seven valve types (intraclass coefficient [ICC], 0.977; 95% confidence interval [CI], 0.962-0.987). The mean differences in opening angles between the CT measurements and the manufacturers' values were 1.2degrees in seven types of valves, 11.0degrees in On-X valves, and 15.5degrees in ATS valves. The manufacturers' closing angles and those measured by CT showed excellent agreement for all valve types (ICC, 0.953; 95% CI, 0.920-0.972). Among valves with suspected dysfunction, those with limitation of motion (LOM) and an increased pressure gradient (PG) had smaller opening angles than those with LOM only (p < 0.05). CONCLUSION: Dual-source cardiac CT accurately measures opening and closing angles in most types of mechanical aortic valves, compared with the manufacturers' values. Opening angles on CT differ according to the type of valve dysfunction and a decreased opening angle may suggest an elevated PG.