The Association of CHADS-P2A2RC Risk Score With Clinical Outcomes in Patients Taking P2Y12 Inhibitor Monotherapy After 3 Months of Dual Antiplatelet Therapy Following Percutaneous Coronary Intervention.

BACKGROUND AND OBJECTIVES: Concerns remain that early aspirin cessation may be associated with potential harm in subsets at high risk of ischemic events. This study aimed to assess the effects of P2Y12 inhibitor monotherapy after 3-month dual antiplatelet therapy (DAPT) vs. prolonged DAPT (12-month or longer) based on the ischemic risk stratification, the CHADS-P2A2RC, after percutaneous coronary intervention (PCI). METHODS: This was a sub-study of the SMART-CHOICE trial. The effect of the randomized antiplatelet strategies was assessed across 3 CHADS-P2A2RC risk score categories. The primary outcome was a major adverse cardiac and cerebral event (MACCE), a composite of all-cause death, myocardial infarction, or stroke. RESULTS: Up to 3 years, the high CHADS-P2A2RC risk score group had the highest incidence of MACCE (105 [12.1%], adjusted hazard ratio [HR], 2.927; 95% confidence interval [CI], 1.358-6.309; p=0.006) followed by moderate-risk (40 [1.4%], adjusted HR, 1.786; 95% CI, 0.868-3.674; p=0.115) and low-risk (9 [0.5%], reference). In secondary analyses, P2Y12 inhibitor monotherapy reduced the Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding without increasing the risk of MACCE as compared with prolonged DAPT across the 3 CHADS-P2A2RC risk strata without significant interaction term (interaction p for MACCE=0.705 and interaction p for BARC types 2, 3, or 5 bleeding=0.055). CONCLUSIONS: The CHADS-P2A2RC risk score is valuable in discriminating high-ischemic-risk patients. Even in such patients with a high risk of ischemic events, P2Y12 inhibitor monotherapy was associated with a lower incidence of bleeding without increased risk of ischemic events compared with prolonged DAPT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02079194.

Prevalence and Prognostic Implications of Worsening Renal Function After Acute Myocardial Infarction.

We sought to investigate the relation between worsening renal function (WRF) at 1-year follow-up and clinical outcomes at 3 years after acute myocardial infarction (AMI). We analyzed data from 13,104 patients enrolled in the national AMI registry from November 2011 to December 2015. Patients with all-cause death, recurrent myocardial infarction (re-MI), and rehospitalization for heart failure at 1-year follow-up after AMI were excluded. A total of 6,235 patients were extracted and divided into WRF and non-WRF groups. WRF was defined as a ≥25% decrease in estimated glomerular filtration rate (eGFR) from baseline to 1-year follow-up. The primary outcome was 3-year major adverse cardiac events, a composite of all-cause death, re-MI, and rehospitalization for heart failure. On average, a -1.5 ml/min/1.73 m2/y rate of decrease in eGFR was exhibited, and 575 patients (9.2%) exhibited WRF at 1-year follow-up. After multiple adjustments, WRF at 1-year follow-up was independently associated with increased risks of major adverse cardiac events (adjusted hazard ratio 1.498, 95% confidence interval 1.113 to 2.016, p = 0.01), all-cause death, and re-MI at 3-year follow-up. Older age, female, diabetes mellitus, hypertension, non-ST-segment elevation AMI, anterior AMI, anemia, left ventricular ejection fraction <35%, and baseline eGFR <30 ml/min/1.73 m2 were identified as independent predictors of WRF after AMI. In conclusion, WRF at 1-year follow-up after AMI intuitively seems like a risk marker indicating multiple co-morbidities. Monitoring serum creatinine in patients at 1-year follow-up after AMI may help to identify those who are at the highest risk and guide effective long-term therapeutics.

Age-related difference in the impact of diabetes mellitus on all-cause mortality after acute myocardial infarction.

AIM: To test the hypothesis that the impact of diabetes mellitus on clinical outcomes after acute myocardial infarction (AMI) can vary by age. METHODS: A total of 12,600 AMI patients from the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) between November 2011 and December 2015 was classified into young (n = 3,590 [29%]) and old (n = 9,010 [72%]). Those less than 55 years of age were considered young. We performed comparisons of baseline characteristics, in-hospital treatments, and 3-year clinical outcomes between patients with and without diabetes after stratification according to age group. RESULTS: The prevalence of diabetes mellitus was 27% in the young AMI group. In the multivariable adjusted model of the entire cohort, diabetes mellitus was associated strongly with 3-year all-cause mortality (13% vs. 6.8%; adjusted hazard ratio [HR], 1.318; 95% confidence interval [CI], 1.138-1.526; P<0.001). When the entire cohort was subdivided into two age groups, young diabetic patients showed a 107% higher mortality rate than those without diabetes (adjusted HR, 2.07 [1.15-3.72];P = 0.015). Meanwhile, old diabetic patients had a 25% higher risk of mortality than non-diabetic patients (adjusted HR, 1.25 [1.08-1.46];P = 0.004). The interaction of diabetes with age was significant (adjusted P for interaction = 0.008). CONCLUSIONS: Diabetes mellitus is not uncommon in younger AMI patients, and the relative risk of 3-year mortality is significantly higher in young patients than in older counterparts. More aggressive treatments are needed to prevent future cardiovascular events in younger patients after AMI.

Gender Differences in All-Cause Mortality after Acute Myocardial Infarction: Evidence for a Gender-Age Interaction.

Gender difference studies in mortality after acute myocardial infarction (AMI) have shown inconsistent results. A total of 13,104 patients from the KAMIR-NIH between November 2011 and December 2015 were classified into young (n = 3837 [29.3%]) and elderly (n = 9267 [70.7%]) patients. For the study, women <65 and men <55 years of age were considered "young". In the adjusted model of the entire cohort, there was no significant difference in three-year all-cause mortality between women and men (17.8% vs. 10.3%; adjusted hazard ratio [HR], 0.953; 95% confidence interval [CI], 0.799-1.137). However, when the entire cohort was subdivided into two age groups, young women showed an 84.3% higher mortality rate than young men (adjusted HR, 1.843; 95% CI, 1.098-3.095). Contrariwise, elderly women patients had a 20.4% lower hazard of mortality compared with elderly men (adjusted HR, 0.796; 95% CI, 0.682-0.929). The interaction of gender with age was significant, even after multiple adjustments (adjusted p for interaction = 0.003). The purpose of this study was to assess whether gender differences depend on the patients' age. Based on our analysis, higher mortality of young women remains even in the contemporary era of AMI. A better understanding of the mechanisms underlying these differences is warranted.

Cytotoxicity of Light-Cured Dental Materials according to Different Sample Preparation Methods.

Dental light-cured resins can undergo different degrees of polymerization when applied in vivo. When polymerization is incomplete, toxic monomers may be released into the oral cavity. The present study assessed the cytotoxicity of different materials, using sample preparation methods that mirror clinical conditions. Composite and bonding resins were used and divided into four groups according to sample preparation method: uncured; directly cured samples, which were cured after being placed on solidified agar; post-cured samples were polymerized before being placed on agar; and "removed unreacted layer" samples had their oxygen-inhibition layer removed after polymerization. Cytotoxicity was evaluated using an agar diffusion test, MTT assay, and confocal microscopy. Uncured samples were the most cytotoxic, while removed unreacted layer samples were the least cytotoxic (p < 0.05). In the MTT assay, cell viability increased significantly in every group as the concentration of the extracts decreased (p < 0.05). Extracts from post-cured and removed unreacted layer samples of bonding resin were less toxic than post-cured and removed unreacted layer samples of composite resin. Removal of the oxygen-inhibition layer resulted in the lowest cytotoxicity. Clinicians should remove unreacted monomers on the resin surface immediately after restoring teeth with light-curing resin to improve the restoration biocompatibility.

Comparing Outcomes Following Salvage Microsurgery in Vestibular Schwannoma Patients Failing Gamma-knife Radiosurgery or Microsurgery.

OBJECTIVE: The increasing use of primary gamma-knife radiosurgery (GKS) for the treatment of vestibular schwannoma (VS) has led to a concomitant increase in the number of patients requiring salvage surgery for GKS failure. When patients underwent GKS as the primary treatment, it is known that dissecting tumor from adjacent nerves during salvage surgery is more difficult. In this report, we share our clinical experience with such patients and analyze the clinical findings of patients with tumor regrowth/recurrence. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary center. PATIENTS: Nine patients who underwent salvage surgery for VS regrowth/recurrence after GKS or microsurgery were enrolled. MAIN OUTCOME MEASURES: Symptom progression, radiological changes, intraoperative findings, and surgical outcomes were evaluated and compared. RESULTS: Six patients with previous GKS and three with previous microsurgery underwent salvage microsurgery. The most obvious symptom of tumor regrowth was aggravation of hearing loss. Salvage surgery in all patients was limited to subtotal or near-total resection via a translabyrinthine/transotic approach. Severe adhesion, thickening, and fibrosis were more prominent findings in the GKS than in the previous microsurgery group. Dissection of the tumor from the facial nerve was more difficult in the GKS than in the microsurgery patients. Despite anatomical preservation of the facial nerve in all the six patients, three in the GKS group, but none in the revision microsurgery group, had worsening of facial nerve function. CONCLUSION: Salvage microsurgery of VS after failed GKS is more difficult than revision microsurgery, and the facial nerve outcomes are relatively poor. Therefore, the primary method of VS treatment should be carefully chosen. Additional imaging studies are recommended in patients with a sudden change in hearing loss who underwent GKS.

Vibration-induced nystagmus in patients with vestibular schwannoma: Characteristics and clinical implications.

OBJECTIVE: To investigate the clinical significance of vibration-induced nystagmus (VIN) in unilateral vestibular asymmetry and vestibular schwannoma. METHODS: Thirteen patients with vestibular schwannoma underwent the VIN test, in which stimulation was applied to the mastoid processes and sternocleidomastoid (SCM) muscles on the ipsilateral and contralateral sides of lesions. Preoperative VIN was measured, and changes in VIN were followed up for 6months after tumor removal. Significance of VIN was determined by evaluation of its sensitivity, correlation with vestibular function tests and tumor volume, and postoperative changes. RESULTS: The overall pre and postoperative sensitivities of VIN were 92.3% and 100%, respectively, considering stimulation at all four sites. Maximum slow-phase velocity (MSPV) of VIN was linearly correlated with caloric weakness and tumor volume, especially when stimulation was applied to the SCM muscle. Postoperative MSPV of VIN exhibited stronger linear correlation with postoperative changes in canal paresis value and inverse correlation with tumor size upon stimulation of the ipsilateral SCM muscle than upon stimulation of other sites. During the 6-month follow-up period, persistence of VIN without changes in MSPV was observed even after vestibular compensation. CONCLUSIONS: Evoking VIN by stimulation of the mastoid processes and SCM muscles is effective for detecting vestibular asymmetry. It could also help determine the degree of vestibular asymmetry and volume of vestibular schwannoma if stimulation is applied to the SCM muscle. SIGNIFICANCE: The results of this study could provide clues for the basic application of VIN in patients with vestibular loss and vestibular schwannoma.

Delivery of dexamethasone from bioactive nanofiber matrices stimulates odontogenesis of human dental pulp cells through integrin/BMP/mTOR signaling pathways.

Therapeutically relevant design of scaffolds is of special importance in the repair and regeneration of tissues including dentin and pulp. Here we exploit nanofiber matrices that incorporate bioactive glass nanoparticles (BGNs) and deliver the odontogenic drug dexamethasone (DEX) to stimulate the odontogenic differentiation of human dental pulp cells (HDPCs). DEX molecules were first loaded onto the BGN, and then the DEX-BGN complex was incorporated within the biopolymer nanofiber matrix through electrospinning. The release of DEX continued over a month, showing a slow releasing profile. HDPCs cultured on the DEX-releasing BGN matrices were viable, proliferating well up to 14 days. The odontogenic differentiation, as assessed by alkaline phosphatase activity, mRNA expression of genes, and mineralization, was significantly stimulated on the matrices incorporating BGN and further on those releasing DEX. The DEX-releasing BGN matrices highly upregulated the expression of the integrin subsets α1, α5, and ß3 as well as integrin downstream signaling molecules, including focal adhesion kinase (FAK), Paxillin, and RhoA, and activated bone morphogenetic protein mRNA and phosphorylation of Smad1/5/8. Furthermore, the DEX-releasing BGN-matrices stimulated Akt and mammalian target of rapamycin (mTOR), which was proven by the inhibition study. Collectively, the designed therapeutic nanofiber matrices that incorporate BGN and deliver DEX were demonstrated to promote odontogenesis of HDPCs, and the integrins, bone morphogenetic protein, and mTOR signaling pathways are proposed to be the possible molecular mechanisms. While further in vivo studies are still needed, the DEX-releasing bioactive scaffolds are considered as a potential therapeutic nanomatrix for regenerative endodontics and tissue engineering.

Height and sex is strongly associated with radial augmentation index in Korean patients with never-treated hypertension.

OBJECTIVES: Central hemodynamics may better represent the load imposed on the coronary and cerebral arteries and thereby bear a stronger relationship to cardiovascular outcomes. METHODS: Patients who had confirmed hypertension as assessed by daytime 24-hour ambulatory blood pressure monitoring (≥135/85 mmHg) were enrolled. Central blood pressure and radial augmentation index (AIx) corrected for a heart rate of 75 bpm (radial AIx 75) were measured for all patients. We evaluated the association of age, height, and sex with central hemodynamics in patients with never-treated hypertension. RESULTS: A total of 203 patients were enrolled, of whom men numbered 101 (49.7%). The median height of all patients was 162 cm, and mean age was 53.2 years. In the Pearson correlation analysis, regardless of sex difference (R=-0.627 for height, R=0.035 for age, P-value =0.005), a stronger relationship was observed between height and radial AIx 75 than between age and radial AIx 75. In the multiple regression analysis, the sex difference and height were strongly associated with elevated radial AIx 75 in all patients (adjusted R (2)=0.428, ß=6.237, 95% confidence interval [CI] for women 1.480-10.995, P-value =0.011 and ß=-0.632, 95% CI for height -0.929 to -0.335, P-value =0.009, respectively). CONCLUSION: In patients with never-treated hypertension, female sex and shorter height are the important risk factors of elevated radial AIx 75.

A mutation of the succinate dehydrogenase B gene in a Korean family with paraganglioma.

Familial paraganglioma (PGL) is a dominantly inherited disorder characterized by development of PGLs in the head and neck region. Germline mutations in genes coding for succinate dehydrogenase (SDH) subunits D, B, and C (SDHD, SDHB, SDHC) are found in almost all familial PGL patients. A 19-year-old female presented with pulsatile tinnitus and a reddish pulsating mass in the external auditory canal, and her mother complained of similar symptoms. Paraganglioma was found in both patients and was surgically removed. We report a case of germline SDHB mutation. This mutation was a deletion of thymine at nucleotide position 757 in exon 7 of the SDHB gene (c.757delT).

Magnetic nanocomposite scaffolds combined with static magnetic field in the stimulation of osteoblastic differentiation and bone formation.

Magnetism has recently been implicated to play significant roles in the regulation of cell responses. Allowing cells to experience a magnetic field applied externally or scaffolding them in a material with intrinsic magnetic properties has been a possible way of utilizing magnetism. Here we aim to investigate the combined effects of the external static magnetic field (SMF) with magnetic nanocomposite scaffold made of polycaprolactone/magnetic nanoparticles on the osteoblastic functions and bone formation. The SMF synergized with the magnetic scaffolds in the osteoblastic differentiation of primary mouse calvarium osteoblasts, including the expression of bone-associated genes (Runx2 and Osterix) and alkaline phosphatase activity. The synergism was demonstrated in the activation of integrin signaling pathways, such as focal adhesion kinase, paxillin, RhoA, mitogen-activated protein kinase, and nuclear factor-kappaB, as well as in the up-regulation of bone morphogenetic protein-2 and phosphorylation of Smad1/5/8. Furthermore, the SMF/magnetic scaffold-stimulated osteoblasts promoted the angiogenic responses of endothelial cells, including the expression of vascular endothelial growth factor and angiogenin-1 genes and the formation of capillary tubes. When the magnetic scaffolds were implanted in mouse calvarium defects, the application of SMF significantly enhanced the new bone formation at 6 weeks, as revealed by the histological and micro-computed tomographic analyses. Current findings suggest that the combinatory application of external (SMF) and internal (scaffold) magnetism can be a promising tool to regenerative engineering of bone.

Combined effects of mineral trioxide aggregate and human placental extract on rat pulp tissue and growth, differentiation and angiogenesis in human dental pulp cells.

OBJECTIVE: The aim of this study was to evaluate the combined effects of mineral trioxide aggregate (MTA) and human placental extract (HPE) on cell growth, differentiation and in vitro angiogenesis of human dental pulp cells (HDPCs) and to identify underlying signal transduction mechanisms. In vivo dental pulp responses in rats for a pulp-capping agent were examined. MATERIALS AND METHODS: MTS assay. ALP activity test, alizarin red S staining and RT-PCR for marker genes were carried out to evaluate cell growth and differentiation. HUVEC migration, mRNA expression and capillary tube formation were measured to evaluate angiogenesis. Signal transduction was analysed using Western blotting and confocal microscopy. The pulps of rat maxillary first molars were exposed and capped with either MTA or MTA plus HPE. Histologic observation and scoring were performed. RESULTS: Compared to treatment of HDPCs with either HPE or MTA alone, the combination of HPE and MTA increased cell growth, ALP activity, mineralized nodules and expression of marker mRNAs. Combination HPE and MTA increased migration, capillary tube formation and angiogenic gene expression compared with MTA alone. Activation of Akt, mammalian target of rapamycin (mTOR), p38, JNK and ERK MAPK, Akt, and NF-κB were significantly increased by combining HPE and MTA compared with MTA alone. Pulp capping with MTA plus HPE in rats showed superior dentin bridge formation, odontoblastic layers and dentinal tubules and lower inflammatory cell response, compared to the MTA alone group. CONCLUSIONS: This study demonstrates for the first time that the use of MTA with HPE promotes cell growth, differentiation and angiogenesis in HDPCs, which were associated with mTOR, MAPK and NF-κB pathways. Direct pulp capping with HPE plus MTA showed superior results when compared with MTA alone. Thus, the combination of MTA and HPE may be useful for regenerative endodontics.

Magnetic Nanocomposite Scaffold-Induced Stimulation of Migration and Odontogenesis of Human Dental Pulp Cells through Integrin Signaling Pathways.

Magnetism is an intriguing physical cue that can alter the behaviors of a broad range of cells. Nanocomposite scaffolds that exhibit magnetic properties are thus considered useful 3D matrix for culture of cells and their fate control in repair and regeneration processes. Here we produced magnetic nanocomposite scaffolds made of magnetite nanoparticles (MNPs) and polycaprolactone (PCL), and the effects of the scaffolds on the adhesion, growth, migration and odontogenic differentiation of human dental pulp cells (HDPCs) were investigated. Furthermore, the associated signaling pathways were examined in order to elucidate the molecular mechanisms in the cellular events. The magnetic scaffolds incorporated with MNPs at varying concentrations (up to 10%wt) supported cellular adhesion and multiplication over 2 weeks, showing good viability. The cellular constructs in the nanocomposite scaffolds played significant roles in the stimulation of adhesion, migration and odontogenesis of HDPCs. Cells were shown to adhere to substantially higher number when affected by the magnetic scaffolds. Cell migration tested by in vitro wound closure model was significantly enhanced by the magnetic scaffolds. Furthermore, odontogenic differentiation of HDPCs, as assessed by the alkaline phosphatase activity, mRNA expressions of odontogenic markers (DMP-1, DSPP,osteocalcin, and ostepontin), and alizarin red staining, was significantly stimulated by the magnetic scaffolds. Signal transduction was analyzed by RT-PCR, Western blotting, and confocal microscopy. The magnetic scaffolds upregulated the integrin subunits (α1, α2, ß1 and ß3) and activated downstream pathways, such as FAK, paxillin, p38, ERK MAPK, and NF-κB. The current study reports for the first time the significant impact of magnetic scaffolds in stimulating HDPC behaviors, including cell migration and odontogenesis, implying the potential usefulness of the magnetic scaffolds for dentin-pulp tissue engineering.

Genetic aspects and clinical characteristics of familial Meniere's disease in a South Korean population.

OBJECTIVES/HYPOTHESIS: This study was undertaken to investigate the prevalence, inheritance patterns, and clinical characteristics of familial Meniere's disease (MD) in a South Korean population. STUDY DESIGN: Direct interviews, telephone interviews, and reviews of the medical records of definite Meniere's disease patients and their families. METHODS: Direct and telephone interviews were performed for 286 definite MD patients and their family members who were suspected of having MD. The diagnosis of MD in family members was made by obtaining a detailed history, performing basic neurotological examinations and reviewing hearing test results. The clinical characteristics as well as the prevalence and inheritance patterns of familial MD were analyzed. RESULTS: The prevalence of familial Meniere-like syndrome (at least one family member with definite MD and other members with probable MD) and definite familial MD (two or more family members with definite Meniere's disease) were 9.8% and 6.3%, respectively, and the most common inheritance pattern was autosomal dominant with incomplete penetrance. The significant clinical characteristics of familial cases were an early disease onset and a higher prevalence of migraines. CONCLUSIONS: This is the first report describing the genetic aspects of MD in a single large Asian population. The prevalence of definite familial MD was 6.3% with an incomplete autosomal dominant inheritance pattern in most cases. Early-onset age and a high prevalence of migraines were significant clinical features of familial MD in this South Korean population. These data could provide a basis for the analysis of the genetic mechanism of familial MD in Asian populations. LEVEL OF EVIDENCE: 4.

Pulmonary artery angiosarcoma confused with acute pulmonary thromboembolism: focusing on clinical and echocardiographic features in the differentiation of two categories.

Although pulmonary artery angiosarcoma is rare, it can be misdiagnosed as pulmonary embolism because of its similar clinical and diagnostic features. The diagnosis is often delayed and the misdiagnosis brings unnecessary treatment. Because we made a wrong diagnosis of pulmonary artery angiosarcoma as an acute pulmonary embolism, we did thrombolytic therapy which could be dangerous to the patient. In this case report, we focused on the clinical and echocardiographic features of pulmonary artery angiosarcoma which can be used in differentiating the diagnosis from pulmonary embolism.

Intracardiac echocardiography to guide biopsy for two cases of intracardiac masses.

Pathologic diagnosis of a cardiac mass is vital in determining the proper treatment modality. Open heart surgery or transesophageal echocardiography guided biopsy can be feasible methods to confirm the pathology. However, the former is highly invasive and both methods require general anesthesia. The introduction of intracardiac echocardiography (ICE) can provide good anatomic information of heart and does not require general anesthesia. In this report, we present two cases of cardiac tumors which were confirmed by percutaneous biopsy under the guidance of an ICE. The patients underwent cardiac biopsy without any complications.

Three-point fix tympanoplasty.

CONCLUSION: The three-point fix tympanoplasty procedure is a stable and effective technique - with a high degree of graft take and satisfactory hearing results - for reconstruction of most tympanic membrane (TM) perforations. OBJECTIVE: It is difficult to repair a TM perforation, including subtotal perforation, involving the anterior part of the annulus. Reperforation can occur when an underlay graft technique is used. An overlay graft technique may result in anterior blunting/lateralization. We introduce a three-point fix tympanoplasty procedure, which can provide additional support to yield a stable graft. METHODS: The study enrolled a total of 234 patients who underwent a three-point fix tympanoplasty procedure from November 2005 to June 2011. Anatomic success was defined as an intact, repaired TM, while functional success was defined as a significant decrease in the air-bone gap at the end of follow-up compared with preoperative hearing (air-bone gap). The complication rate was also analyzed. RESULTS: The anatomic success rate was 93.2% (218/234 patients). The functional success rate after an average of 1 year was 73.5%. The postoperative average pure-tone air-bone gap (15.4 ± 11.4 dB) decreased successfully in comparison with the preoperative average air-bone gap (20.6 ± 12.1 dB). There were few postoperative complications (7.7%).

BMP-2 promotes oral squamous carcinoma cell invasion by inducing CCL5 release.

Bone morphogenetic protein-2 (BMP-2)-containing bone grafts are useful regenerative materials for oral and maxillofacial surgery; however, several in vitro and in vivo studies previously reported cancer progression-related adverse effects caused by BMP-2. In this study, by quantifying the rhBMP-2 content released from bone grafts, the rhBMP-2 concentration that did not show cytotoxicity in each cell line was determined and applied to the in vitro monoculture or coculture model in the invasion assay. Our results showed that 1 ng/ml rhBMP-2, while not affecting cancer cell viability, significantly increased the invasion ability of the cancer cells cocultured with fibroblasts. Cocultured medium with rhBMP-2 also contained increased levels of matrix metalloproteinases. rhBMP-2-treated cocultured fibroblasts did not show a prominent difference in mRNA expression profile. Some cytokines, however, were detected in the conditioned medium by a human cytokine antibody array. Among them, the cancer invasion-related factor CCL5 was quantified by ELISA. Interestingly, CCL5 neutralizing antibodies significantly reduced the invasion of oral cancer cells. In conclusion, our results suggest that 1 ng/ml rhBMP-2 may induce invasion of oral squamous cell carcinoma (OSCC) cells by CCL5 release in coculture models. Therefore, we propose that a careful clinical examination before the use of rhBMP-2-containing biomaterials is indispensable for using rhBMP-2 treatment to prevent cancer progression.

A comparison of different techniques of two-dimensional speckle-tracking strain measurements of right ventricular systolic function in patients with acute pulmonary embolism.

BACKGROUND: Speckle-tracking echocardiography has been applied to measure right ventricular (RV) systolic function in various diseases. However, variations in strain measurement by different vendors have limited the application of these techniques for assessment of RV function. We sought to compare two methods for the assessment of RV systolic function in patients with acute pulmonary embolism (PE). METHODS: From August 2007 to May 2011, all consecutive PE patients were prospectively included in this cohort study. Global longitudinal strains of RV measured with EchoPAC PC software (GLSRV-EchoPAC; GE Medical Systems) and velocity vector imaging (GLSRV-VVI; Siemens Medical Systems) were recorded on the same set of echocardiographic images. RESULTS: We analyzed a total of 50 patients (12 males, 68 ± 14 years) with acute PE in this study. GLSRV-EchoPAC and GLSRV-VVI were correlated (r = 0.793, p < 0.001) and they showed significant correlations with conventional echocardiographic parameters of RV systolic function and Log B-type natriuretic peptide (BNP) level. However, GLSRV-VVI only showed significant correlations with cardiac biomarkers as serum creatinine kinase-MB (r = 0.367, p = 0.010) and tropoinin-I concentrations (r = 0.294, p = 0.040). CONCLUSION: GLSRV-VVI and GLSRV-EchoPAC showed significant correlations with conventional echocardiographic parameters of RV systolic function and LogBNP value in patients with PE.