Visualization of coronary plaque in type 2 diabetes mellitus patients using a new 40MHz intravascular ultrasound imaging system

SummaryBackgroundPrevious epidemiological studies demonstrated plaque vulnerability to be high in diabetic patients. iMap-intravascular ultrasound (IVUS) is a recently developed radiofrequency 40MHz IVUS imaging system for tissue characterization. This study aimed to characterize coronary plaque in target lesions of diabetic patients using iMap-IVUS.MethodsWe studied 175 treated vessels in 146 patients with stable angina pectoris and analyzed plaque components of culprit lesions by iMAP-IVUS. Patients were divided into 2 groups: non-diabetic (non-DM: 112 vessels, 93 patients) and diabetic (DM: 63 vessels, 53 patients).ResultsIn gray-scale IVUS 2D analysis, there were no differences in IVUS parameters. In 3D analysis, the DM group tended to have a larger plaque volume (p=0.07) and plaque burden (p=0.10). At minimum lumen sites, the absolute lipidic and necrotic areas (0.84±0.44mm2 vs. 0.58±0.41mm2, p<0.001, and 2.42±1.65mm2 vs. 1.46±1.76mm2, p<0.001, respectively) and percent lipidic and necrotic areas were significantly greater in the DM than in the non-DM group (8.39±3.38% vs. 5.25±2.30%, p<0.0001, and 23.65±11.54% vs. 12.99±10.71%, p<0.0001, respectively). In addition, the absolute lipidic and necrotic volumes (11.75±10.59mm3 vs. 8.18±6.24mm3, p<0.01, and 29.99±28.90mm3 vs. 19.44±19.35mm3, p<0.01, respectively) and percent lipidic and necrotic volumes were significantly greater in the DM than in the non-DM group (6.27±1.92% vs. 5.13±1.82%, p<0.0001, and 16.54±7.56% vs. 12.08±6.05%, p<0.0001, respectively).ConclusionCharacterization of coronary plaque by iMAP-IVUS in diabetic patients showed increased lipidic amount and necrotic plaque volume relative to subjects without DM

Relationship between tissue characterization with 40MHz intravascular ultrasound imaging and 64-slice computed tomography

AbstractBackgroundIdentification of coronary plaque composition is important for selecting the treatment strategy, and 64-slice computed tomography (CT) is a noninvasive method of characterizing atherosclerotic plaques. However, the correlation between plaque characteristics detected by CT and intravascular ultrasound (IVUS) is not clear. A 40MHz IVUS imaging system (iMap-IVUS) has recently been developed to evaluate plaque composition. The aim of this study was to compare iMap-IVUS with 64-slice CT angiography for the characterization of non-calcified coronary plaques.Methods and resultsBoth 64-slice CT angiography and iMap-IVUS were performed in 19 patients (38 plaques). CT values were measured as Hounsfield units (HU) in circular regions of interest (ROI) drawn on the plaques. The iMap-IVUS system analyzed coronary plaques as fibrotic, lipidic, necrotic, or calcified tissue based on the radiofrequency spectrum.A positive correlation was found between CT values and the percentage of fibrotic plaque (r=0.34, p=0.036) or calcified plaque (r=0.40, p=0.011). Conversely, a negative correlation was found between CT values and the percentage of lipidic plaque (r=−0.41, p=0.01), or necrotic plaque (r=−0.41, p=0.01).ConclusionsGood correlations were observed between the characteristics of non-calcified plaque determined by iMap-IVUS and the CT values of plaque detected by 64-slice CT scanning

Locomotive syndrome is associated with body composition and cardiometabolic disorders in elderly Japanese women

The 25-question Geriatric Locomotive Function Scale [7]. (DOCX 154 kb

The Relationship between Locomotive Syndrome and Depression in Community-Dwelling Elderly People

Locomotive syndrome (LS) is a concept that refers to the condition of people requiring healthcare services because of problems associated with locomotion. Depression is a major psychiatric disease among the elderly, in addition to dementia. The purpose of this study was to determine the association between LS and depression. The study participants were 224 healthy elderly volunteers living in a rural area in Japan. LS was defined as scores ≥ 16 on the 25-question Geriatric Locomotive Function Scale (GLFS-25). Depression was defined as scores ≥ 5 on the 15-item Geriatric Depression Scale (GDS-15). Height and body weight were measured. The prevalence of LS and depression was 13.9% and 24.2%, respectively. Compared with the non-LS group, the LS group was older, was shorter, had a higher BMI, and had higher GDS-15 scores. Logistic regression analysis showed that participants with GDS-15 scores ≥ 6 had higher odds for LS than those with GDS-15 scores < 6 (odds ratio [OR] = 4.22). Conversely, the depression group had higher GLFS-25 scores than the nondepression group. Participants with GLFS-25 scores ≥ 5 had higher odds for depression than those with GLFS-25 scores < 5 (OR = 4.53). These findings suggest that there is a close relationship between LS and depression

The Results of a New Distal Protection Method in Intervention for Chronic Total Occlusion of the Superficial Femoral Artery

Aims. To determine the efficacy of a new distal protection method in SFA CTO interventions. Methods and Results. From June 2003 to February 2009, ninety-two consecutive, chronic total occlusions of superficial femoral arteries were treated with catheter-based intervention using a bidirectional approach. Nine of these cases were managed with our original, distal protection method, based on symptoms, angiographic images, wire resistance, and intravascular ultrasound images. The average age was 73 years; eight patients were male. The mean occlusion length was 17.1 cm. A distal protection balloon was inserted from the retrograde sheath in the popliteal artery and placed distal to the occluded lesion after successful wire crossing. Lesion dilatation with a balloon was performed antegradely and debris was removed by 6Fr. guiding catheter. Debris was retrieved from all lesions, consisting mainly of thrombus. Where we decided not to use the distal protection method, there was no distal thromboembolism. Conclusion. In SFA-CTO intervention, the risk of distal embolization is 10%, which can be anticipated and eliminated by the distal protection method

CCL2 as a potential therapeutic target for clear cell renal cell carcinoma

We previously reported that the pVHL-atypical PKC-JunB pathway contributed to promotion of cell invasiveness and angiogenesis in clear cell renal cell carcinoma (ccRCC), and we detected chemokine (C-C motif) ligand-2 (CCL2) as one of downstream effectors of JunB. CCL2 plays a critical role in tumorigenesis in other types of cancer, but its role in ccRCC remains unclear. In this study, we investigated the roles and therapeutic potential of CCL2 in ccRCC. Immunohistochemical analysis of CCL2 expression for ccRCC specimens showed that upregulation of CCL2 expression correlated with clinical stage, overall survival, and macrophage infiltration. For functional analysis of CCL2 in ccRCC cells, we generated subclones of WT8 cells that overexpressed CCL2 and subclones 786-O cells in which CCL2 expression was knocked down. Although CCL2 expression did not affect cell proliferation in vitro, CCL2 overexpression enhanced and CCL2 knockdown suppressed tumor growth, angiogenesis, and macrophage infiltration in vivo. We then depleted macrophages from tumor xenografts by administration of clodronate liposomes to confirm the role of macrophages in ccRCC. Depletion of macrophages suppressed tumor growth and angiogenesis. To examine the effect of inhibiting CCL2 activity in ccRCC, we administered CCL2 neutralizing antibody to primary RCC xenografts established from patient surgical specimens. Inhibition of CCL2 activity resulted in significant suppression of tumor growth, angiogenesis, and macrophage infiltration. These results suggest that CCL2 is involved in angiogenesis and macrophage infiltration in ccRCC, and that CCL2 could be a potential therapeutic target for ccRCC

Functional and genomic characterization of patient‐derived xenograft model to study the adaptation to mTORC1 inhibitor in clear cell renal cell carcinoma

Resistance to the mechanistic target of rapamycin (mTOR) inhibitors, which are a standard treatment for advanced clear cell renal cell carcinoma (ccRCC), eventually develops in most cases. In this study, we established a patient-derived xenograft (PDX) model which acquired resistance to the mTOR inhibitor temsirolimus, and explored the underlying mechanisms of resistance acquisition. Temsirolimus was administered to PDX model mice, and one cohort of PDX models acquired resistance after repeated passages. PDX tumors were genetically analyzed by whole-exome sequencing and detected several genetic alterations specific to resistant tumors. Among them, mutations in ANKRD12 and DNMT1 were already identified in the early passage of a resistant PDX model, and we focused on a DNMT1 mutation as a potential candidate for developing the resistant phenotype. While DNMT1 expression in temsirolimus-resistant tumors was comparable with the control tumors, DNMT enzyme activity was decreased in resistant tumors compared with controls. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9-mediated heterozygous knockdown of DNMT1 in the temsirolimus-sensitive ccRCC (786-O) cell line was shown to result in a temsirolimus-resistant phenotype in vitro and in vivo. Integrated gene profiles using methylation and microarray analyses of PDX tumors suggested a global shift for the hypomethylation status including promotor regions, and showed the upregulation of several molecules that regulate the mTOR pathway in temsirolimus-resistant tumors. Present study showed the feasibility of PDX model to explore the mechanisms of mTOR resistance acquisition and suggested that genetic alterations, including that of DNMT1, which alter the methylation status in cancer cells, are one of the potential mechanisms of developing resistance to temsirolimus

Region of hadron-quark mixed phase in hybrid stars

Hadron--quark mixed phase is expected in a wide region of the inner structure of hybrid stars. However, we show that the hadron--quark mixed phase should be restricted to a narrower region to because of the charge screening effect. The narrow region of the mixed phase seems to explain physical phenomena of neutron stars such as the strong magnetic field and glitch phenomena, and it would give a new cooling curve for the neutron star.Comment: to be published in Physical Review