Prognostic impact of lipid contents on the target lesion in patients with drug eluting stent implantation

We sought to determine the morphologic predictors of major adverse cardiac events (MACEs) after successful percutaneous coronary intervention (PCI) with drug-eluting stents (DES), using integrated backscatter intravascular ultrasound (IB-IVUS). Conventional IVUS and IB-IVUS were performed in 260 consecutive patients who underwent PCI with DES. Three-dimensional analyses were performed to determine plaque volume and the volume of each plaque component (lipid, fibrous, and calcification). Patients were divided into two groups according to the median lipid volume (LV) in the target lesion. MACEs were defined as death, nonfatal myocardial infarction, and any repeat revascularization. The median follow-up interval was 1285 days. MACEs were observed in 64 patients (24.6 %). Patients having a larger LV compared with their counterparts had worse long-term clinical outcomes regarding mortality (3.8 vs. 0 %, P = 0.02) and MACEs (31.5 vs. 17.7 %, P = 0.008) by log-rank test. After adjustment for confounders, large LV (odds ratio 1.95, 95 % confidence interval 1.14–3.33, P = 0.02) was significantly and independently associated with MACEs. The assessment of coronary plaque characteristics in the target lesion may be useful to predict long-term outcome following successful coronary intervention.     

Proposal of a Parameter for OATP1B1 Inhibition Screening at the Early Drug Discovery Stage

It is known that potent inhibition of organic-anion-transporting polypeptide (OATP)1B1 increases exposure to statins, leading to severe adverse effects. The aim of this study was to propose a parameter and its criteria in OATP1B1 inhibition assay at the early drug discovery stage to avoid compounds with the risk of statin-related adverse effects. According to drug label information, most compounds classified as “contraindicated” or “should be avoided” when administered concomitantly with statins increased their AUCs more than 4-fold. Generally, R values where R = 1 + plasma unbound fraction (fu) × maximum inhibitor concentration at the inlet to the liver/IC₅₀ are used to evaluate the extent of clinical drug interaction. However, clinical doses and C_max cannot be determined at the screening stage. Therefore, we estimated the correlations between change in AUC of statins concomitantly administered with OATP1B1 inhibitors and various parameters including fu/IC₅₀. Cyclosporin A, rifampicin, and telaprevir increased the AUC of statins more than 4-fold and fu/IC₅₀ of these compounds was >0.1 L/μmol. On the other hand, fu/IC₅₀ of other compounds was ≤0.03 L/μmol. This study indicates that fu/IC₅₀ is a useful parameter to avoid compounds that seriously affect statin potency through interaction with OATP1B1 at the screening stage.     

Effects of nasal obstruction on maturation of the jaw-opening reflex in growing rats

Objective

Nasal obstruction during growth changes craniofacial morphology and function. However, the etiological mechanisms of these changes are unknown. The aim of the present study was to investigate the effects of nasal obstruction during growth on the maturation of the jaw-opening reflex (JOR) using an electrophysiological technique. We focused on the oral sensory receptors that regulate the activities and reflexes of the orofacial muscles.

Design

Sixty 6-day-old male Wistar rats were randomly divided into control and experimental groups (n = 30 each). The experimental group underwent unilateral nasal obstruction at 8 days of age. The JOR was evoked by bilateral, low-intensity electrical stimulation of the inferior alveolar nerve. The electromyographic responses were recorded bilaterally from the digastric muscles at 5, 7, and 9 weeks of age.

Results

The latency of the JOR was significantly longer and the peak-to-peak amplitude was significantly smaller in the experimental group than in the control group at each age, while the duration was not significantly different. Intragroup comparison of the latency, peak-to-peak amplitude, and duration at 5, 7, and 9 weeks of age revealed no significant differences in either the control or experimental groups.

Conclusions

Unilateral nasal obstruction during growth may have significant effects on maturation of craniofacial function.     

A Novel Data Mining Approach to the Identification of Effective Drugs or Combinations for Targeted Endpoints—Application to Chronic Heart Failure as a New Form of Evidence-based Medicine

Summary Background: Data mining is a technique for discovering useful information hidden in a database, which has recently been used by the chemical, financial, pharmaceutical, and insurance industries. It may enable us to detect the interesting and hidden data on useful drugs especially in the field of cardiovascular disease.Methods: & Results: We evaluated the current treatments for chronic heart failure (CHF) in our institute using a decision tree method of data mining and compared the results with those of large-scale clinical trials. We enrolled 1,100 patients with CHF (NYHA classes II–IV and EF < 40%) who were hospitalized at the National Cardiovascular Center during the past 31 months. Drugs prescribed at discharge were extracted from the clinical database. Both echocardiograms and plasma BNP level at 6–12 months after discharge were determined prospectively. It was found that beta-blockers, angiotensin converting enzyme inhibitors, and angiotensin II receptor antagonists independently improve both the plasma BNP level and %fractional shortening (FS), while oral inotropic agents increased the plasma BNP level and decreased %FS. These findings agree with evidence accumulated from several large-scale trials. Interestingly, statins, histamine receptor blockers, and alpha-glucosidase inhibitors also attenuated the severity of CHF, suggesting the possibility of new treatment of CHF.Conclusion: Clinical data mining using Japanese CHF patients yielded almost identical data to the results of large-scale trials, and also suggested novel and unexpected candidates for CHF therapy. Further validation of the data mining approved in the cardiovascular field is warranted.     

Properties of Magnetic Garnet Films for Flexible Magneto-Optical Indicators Fabricated by Spin-Coating Method

Non-destructive testing using a magneto-optical effect is a high-resolution non-destructive inspection technique for a metallic structure. It is able to provide high-spatial resolution images of defects. Previously, it has been difficult to fabricate flexible magneto-optical sensors because thermal treatment is necessary to crystallize the magnetic garnet. Therefore, it was not possible to apply magneto-optical imaging to complicated shapes in a test subject, such as a curved surface. In this study, we developed a new process for deposition of the magnetic garnet on the flexible substrate by applying the magnetic garnet powders that have already undergone crystallization. In this new process, as it does not require thermal treatment after deposition, flexible substrates with low heat resistance can be used. In this paper, we report our observations of the optical properties, magnetic hysteresis loop, crystallizability and density of the particles on the flexible substrate deposited by the spin-coating method.     

Benefits of robotically-assisted surgery for complex mitral valve repair

OBJECTIVESTo determine whether robotic mitral valve repair can be applied to more complex lesions compared with minimally invasive direct mitral valve repair through a right thoracotomy. Open in a separate windowMETHODSWe enrolled 335 patients over a 9-year period; 95% of the robotic surgeries were performed after experience performing direct mitral valve repair.RESULTSThe mean age in the robotic versus thoracotomy repair groups was 61 ± 14 vs 55 ± 11 years, respectively (P < 0.001); 97% vs 100% of the patients, respectively, had degenerative aetiologies. Repair complexity was simple in 106 (63%) vs 140 (84%), complex in 34 (20%) vs 20 (12%) and most complex in 29 (17%) vs 6 (4%) patients undergoing robotic versus thoracotomy repair, respectively. The average complexity score with robotic repair was significantly higher versus thoracotomy repair (P < 0.001). The robotic group underwent more chordal replacement using polytetrafluoroethylene and less resections. All patients underwent ring annuloplasty. Cross-clamp time did not differ between the groups, and no strokes or deaths occurred. More patients undergoing robotic repair underwent concomitant procedures versus the thoracotomy group (30% vs 14%, respectively; P < 0.001). The overall repair rate was 100%, with no early mortality or strokes in either group. Postoperative mean residual mitral regurgitation was 0.3 in both groups, and the mean pressure gradient through the mitral valve was 2.4 vs 2.7 mmHg (robotic versus thoracotomy repair, respectively; P = 0.031).CONCLUSIONSRobotic surgery can be applied to repair more complex mitral lesions, with excellent early outcomes.     

Rapid decrease in serum VEGF-A levels may be a worse prognostic biomarker for patients with platinum-resistant recurrent ovarian cancer treated with bevacizumab and gemcitabine

The aim of this study was to investigate the association between changes in the levels of vascular endothelial growth factors (VEGFs) after treatment with bevacizumab and gemcitabine (Bev-Gem) and the clinical outcome. Platinum-resistant ovarian cancer patients treated with Bev-Gem therapy at our hospital between 2014 and 2018 were identified. Serum VEGF levels at the first and second treatment cycle were measured by ELISA. All patients were categorized into two groups—patients with > 50% decrease in serum VEGF-A levels (Group A) and patients with < 50% decrease serum VEGF-A levels (Group B). The association between clinical outcome and serum VEGF levels was investigated between the two groups. Among 18 patients, 10 were in Group A and 8 in Group B. Group A exhibited a lower response rate (0% vs.75% p < 0.01) and clinical benefit rate (60% vs.100% p = 0.02) than Group B. The median serum VEGF-A level of Group A before the first cycle of Bev-Gem therapy was higher than that in Group B (61.2 vs. 3.7 pg/mL, p < 0.01). Group A exhibited worse PFS (7 vs., 10 months, p < 0.01) and OS (17 vs. 26 months, p = 0.04) than Group B. There were more patients with > 10% increase in serum VEGF-B levels in Group A than in Group B (p < 0.01). The rapid decrease in VEGF-A levels and the resultant increase in serum VEGF-B levels might be associated with an unfavorable clinical outcome. Large-scale studies are needed to further examine these results.