Advances in the Management of Coronary Chronic Total Occlusions

Chronic total occlusions (CTOs) have been called “the last frontier” of percutaneous coronary intervention (PCI) due to traditionally low success rates and high risk for restenosis and re-occlusion. Recent advances in equipment and crossing techniques have significantly increased CTO PCI success rates while maintaining low risk of complications. Specifically, the retrograde approach and controlled antegrade dissection and re-entry in conjunction with advanced guidewires and microcatheters have significantly improved procedural success rates. Moreover, the introduction of the “hybrid” approach has created a unified framework for operators to approach CTOs in a systematic and efficient fashion. Finally, drug-eluting stents, especially second generation, have improved long-term patency after CTO PCI.     

An overview of hypertension and cardiac involvement in Asia: Focus on heart failure

Cardiovascular Disease (CVD) is the leading cause of deaths worldwide, contributing to about 30% of all deaths. Half of the cases of CVD are estimated in Asia, the world's most populous continent. Hypertension, a major modifiable risk factor for CVD, results in more deaths than any other CV risk factors in the Asian regions. The total number of patients with hypertension is likely to grow as the population ages. The proportion of the elderly population aged 65 years or more in Asia is expected to increase from 7.4% in 2015 to 10.9% in 2030. It is important to note that more than half (54%) of the world's population live in Asia. Aside of being the biggest single risk factor for global deaths, hypertension is also an important precursor and most common risk factor of heart failure (HF). An increase in HF prevalence is clearly related to the rapid epidemiological transition caused by changes in lifestyle in Asian countries. However, the availability of data on HF burden and health care delivery is limited in Asia compared with Europe and North America. This reality has driven the working group of Asian experts for example the HOPE Asia Network to concentrate on hypertension as risk factors for CVD, with the mission to improve the management of hypertension resulting in organ protection toward a goal of achieving “ZERO” CV event in Asia. This paper aims to give an overview regarding the heart problems caused by hypertension in Asia, focus on HF.     

Diversity of and initiatives for hypertension management in Asia—Why we need the HOPE Asia Network

The Hypertension Cardiovascular Outcome Prevention and Evidence in Asia (HOPE Asia) Network was set up to improve the management of hypertension in Asia with the ultimate goal of achieving “zero” cardiovascular events. Asia is a diverse continent, and the prevalence of hypertension has increased over the last 30 years. There are a number of Asia‐specific features of hypertension and hypertension‐related cardiovascular complications, which means that a region‐specific approach is needed. White‐coat hypertension will become more of an issue over time as Asian populations age, and masked hypertension is more prevalent in Asian than in Western countries. Identifying and treating masked hypertension is important to reduce cardiovascular risk. Abnormal patterns of blood pressure (BP) variability common in Asia include exaggerated early morning BP surge and nocturnal hypertension. These are also important cardiovascular risk factors that need to be managed. Home blood pressure monitoring (HBPM) is an important tool for detecting white‐coat and masked hypertension, and monitoring BP variability, and practices in Asia are variable. Use of HBPM is important given the Asia‐specific features of hypertension, and strategies are needed to improve and standardize HBPM usage. Development of HBPM devices capable of measuring nocturnal BP along with other information and communication technology‐based strategies are key developments in the widespread implementation of anticipation medicine strategies to detect and prevent cardiovascular events in patients with hypertension. Region‐wide differences in hypertension prevalence, control, and management practices in Asia highlight the importance of information sharing to facilitate best practices.     

Modified subintimal transcatheter withdrawal: A novel technique for hematoma decompression to facilitate distal reentry during coronary chronic total occlusion recanalization

A controlled antegrade dissection and reentry technique is the most commonly employed crossing strategy for long coronary chronic total occlusions. The development of compressive hematoma is a recognized complication and results in the impairment of distal vessel visualization and hinders successful reentry attempts. We describe a novel technique utilizing a widely available microcatheter to decompress the subintimal hematoma to restore distal visualization and allow successful reentry.     

Correlation between secosteroid-induced vitamin D receptor activity in melanoma cells and computer-modeled receptor binding strength

To define the interaction of novel secosteroids produced by the action of cytochrome P450scc with vitamin D receptor (VDR), we used a human melanoma line overexpressing VDR fused with enhanced green fluorescent protein (EGFP) and tested the ligand induced translocation of VDR from the cytoplasm to the nucleus. Hydroxyderivatives of vitamin D(3) with a full length (D(3)) side chain and hydroxy-secosteroids with a shortened side chain (pD) stimulated VDR translocation and inhibited proliferation, however, with different potencies. In general the D(3) were more potent than pD analogues. Molecular modeling of the binding of the secosteroids to the VDR genomic binding pocket (G-pocket) correlated well with the experimental data for VDR translocation. In contrast, docking scores for the non-genomic binding site of the VDR were poor. In conclusion, both the length of the side chain and the number and position of hydroxyl groups affect the activation of VDR by novel secosteroids.     

Patterns of subjective quality of life among older adults in rural Vietnam and Indonesia

Aim: This paper aims to assess the subjective quality of life (SQOL) and its correlates among older adults in rural communities of Vietnam and Indonesia. Methods: The paper uses the data from the INDEPTH/WHO Study on global aging and adult health (SAGE). The study was carried out in the FilaBavi Health and Demographic Surveillance System (HDSS) site in Vietnam and in Purworejo HDSS in Indonesia. All people aged 50 years and over who lived in these two HDSS areas were surveyed. Face‐to‐face household interviews were carried out by trained surveyors using the standardized summary version of the INDEPTH/WHO SAGE questionnaire. The SQOL was assessed by asking the respondents “How would you rate your overall quality of life?” The response set was a five‐point scale where 1 = Very good, 2 = Good, 3 = Moderate, 4 = Bad, 5 = Very bad. Results: In both countries, the SQOL was reported to be higher among (i) men; (ii) people with higher education; (iii) people who were in a marital partnership; (iv) people who lived with other family members; and (v) those with higher economic status, compared with that in those of other category(ies) of the same characteristic. In Vietnam, people who belonged to the second to fifth economic quintiles and had more than 6 years of education were sevenfold more likely to report very good/good quality of life compared with those who belonged to the first economic quintile (poorest) and had no formal education. The corresponding figure was 2.7 for Indonesia. Conclusions: The patterns of sociodemographic determinants of SQOL show that inequality in quality of life exists among older adults in the two study settings. Geriatr Gerontol Int 2012; 12: 397–404.     

Electrodeposited nickel–graphene nanocomposite coating: effect of graphene nanoplatelet size on its microstructure and hardness

In this study, the effect of graphene nanoplatelet (GNP) size on the microstructure and hardness of the electrodeposited nickel–graphene nanocomposite coatings were investigated. GNPs with different sizes were prepared by using a high energy ball milling technique. The experimental result revealed the high energy ball milling technique could reduce the size, increase the surface area, and improve the dispersion ability of GNPs. The microstructure, hardness, and components of the nanocomposite coatings were greatly affected by GNP sizes. The highest microhardness was measured to be 273 HV for the nanocomposite coatings containing 5 h-milled GNPs, which is increased up to ∼47% compared to pristine Ni coating. The enhancement in the hardness is attributed to the uniform dispersion of the small GNP sizes inside the Ni matrix and the Ni grain size reduction when using milled GNPs.

The effect of graphene nanoplatelet size on the microstructure and hardness of electrodeposited nickel–graphene nanocomposite coatings was investigated.     

Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone,the murine model of X‐linked hypophosphatemia

X‐linked hypophosphatemia (XLH/HYP)—with renal phosphate wasting, hypophosphatemia, osteomalacia, and tooth abscesses—is caused by mutations in the zinc‐metallopeptidase PHEX gene (phosphate‐regulating gene with homologies to endopeptidase on the X chromosome). PHEX is highly expressed by mineralized tissue cells. Inactivating mutations in PHEX lead to distal renal effects (implying accumulation of a secreted, circulating phosphaturic factor) and accumulation in bone and teeth of mineralization‐inhibiting, acidic serine‐ and aspartate‐rich motif (ASARM)‐containing peptides, which are proteolytically derived from the mineral‐binding matrix proteins of the SIBLING family (small, integrin‐binding ligand N‐linked glycoproteins). Although the latter observation suggests a local, direct matrix effect for PHEX, its physiologically relevant substrate protein(s) have not been identified. Here, we investigated two SIBLING proteins containing the ASARM motif—osteopontin (OPN) and bone sialoprotein (BSP)—as potential substrates for PHEX. Using cleavage assays, gel electrophoresis, and mass spectrometry, we report that OPN is a full‐length protein substrate for PHEX. Degradation of OPN was essentially complete, including hydrolysis of the ASARM motif, resulting in only very small residual fragments. Western blotting of Hyp (the murine homolog of human XLH) mouse bone extracts having no PHEX activity clearly showed accumulation of an ～35 kDa OPN fragment that was not present in wild‐type mouse bone. Immunohistochemistry and immunogold labeling (electron microscopy) for OPN in Hyp bone likewise showed an accumulation of OPN and/or its fragments compared with normal wild‐type bone. Incubation of Hyp mouse bone extracts with PHEX resulted in the complete degradation of these fragments. In conclusion, these results identify full‐length OPN and its fragments as novel, physiologically relevant substrates for PHEX, suggesting that accumulation of mineralization‐inhibiting OPN fragments may contribute to the mineralization defect seen in the osteomalacic bone characteristic of XLH/HYP. © 2013 American Society for Bone and Mineral Research.     

Plasma Cytokine Analysis in Patients with Advanced Extremity Melanoma Undergoing Isolated Limb Infusion

Background

Preprocedure clinical and pathologic factors have failed to consistently differentiate complete response (CR) from progressive disease (PD) in patients after isolated limb infusion (ILI) with melphalan for unresectable in-transit extremity melanoma.

Methods

Multiplex immunobead assay technology (Milliplex MAP Human Cytokine/Chemokine Magnetic Bead Panel, Millipore Corp., Billerica, MA; and Magpix analytical test instrument, Luminex Corp., Austin, TX) was performed on pre-ILI plasma to determine concentrations of selected cytokines (MIP-1α, IL-1Rα, IP-10, IL-1β, IL-1α, MCP-1, IL-6, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β) on a subset of patients (n = 180) who experienced CR (n = 23) or PD (n = 24) after ILI. Plasma from normal donors (n = 12) was also evaluated.

Results

Of 180 ILIs performed, 28 % (95 % confidence interval 22–35, n = 50) experienced a CR, 14 % (n = 25) experienced a partial response, 11 % (n = 21) had stable disease, 34 % (n = 61) had PD, and 13 % (n = 23) were not evaluable for response. Tumor characteristics and pharmacokinetics appeared similar between CR (n = 23) and PD (n = 24) patients who underwent cytokine analysis. Although there were no differences in cytokine levels between CR and PD patients, there were differences between the melanoma patients and controls. MIP-1α, IL-1Rα, IL-1β, IL-1α, IL-17, EGF, IL-12p40, VEGF, GM-CSF, and MIP-1β were significantly higher in normal controls compared to melanoma patients, while IP-10 was lower (p < 0.001) in controls compared to melanoma patients.

Conclusions

Patients with unresectable in-transit melanoma appear to have markedly decreased levels of immune activating cytokines compared to normal healthy controls. This further supports a potential role for immune-targeted therapies and immune monitoring in patients with regionally advanced melanoma.