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Objectives: Determine the rate of malignant transformation (MT) of oral potentially malignant disorders (OPMDs) and risk factors for transformation., Study Design: The OPMD database (2001-2015) from 2 biopsy services in Ontario, Canada, was linked to the Ontario Cancer Registry to determine the rate of progression to oral squamous cell carcinoma (OSCC). Clinical and histologic features of progressed and non-progressed cases were compared to determine risk factors for progression., Results: The MT rate was 6.4% (322/5,036 cases). The mean time for cancer development was 51.2 months. 33.6% of cases (107/322) progressed after over 60 months. The risk of cancer increased with age and was higher in non-smokers. The MT rate was highest in the tongue (11.4%), followed by the floor of mouth (7.1%) and gingiva (6.5%). Histologic grade was associated with progression to cancer (P < .0001). Atypical verrucous-papillary lesions with no or mild dysplasia predominantly affected older patients' gingiva, and the progression rate was significantly higher than conventional mild dysplasia (9.2% vs 3.2%, P = .0002)., Conclusions: Our population-based retrospective study showed that <10% of OPMDs progressed to cancer, which could take many years. Atypical papillary-verrucous proliferation without high-grade dysplasia is a subtype of OPMD requiring further study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Oral carcinogenesis represents a multi-stage process which encompasses several genetic and molecular changes that promote the progression of oral potentially malignant disorders (OPMDs) to oral squamous cell carcinomas (OSCCs). A better understanding of critical pathways governing the progression of OMPDs to OSCCs is critical to improve oncologic outcomes in the future. Previous studies have identified an important role of tumor necrosis factor α (TNFα) and TNF receptor 1 (TNFR1) in the invasiveness of oral cancer cell lines. Here, we investigate the expression of TNFα and TNFR1 in human OPMDs that progress to OSCC compared to non-progressing OPMDs utilizing fluorescent immunohistochemistry (FIHC) to show increased TNFα/TNFR1 expression in progressing OPMDs. In order to interrogate the TNFα/TNFR1 signaling pathway, we utilized a 4-nitroquinoline 1-oxide (4-NQO) mouse model of oral carcinogenesis to demonstrate that TNFα/TNFR1 expression is upregulated in 4-NQO-induced OSCCs. TNFα neutralization decreased serum cytokines, inhibited the development of invasive lesions and reduced tumor-associated neutrophils in vivo . Combined, this data supports the role of TNFα in oral malignant transformation, suggesting that critical immunoregulatory events occur downstream of TNFR1 leading to malignant transformation. Our results advance the understanding of the mechanisms governing OSCC invasion and may serve as a basis for alternative diagnostic and therapeutic approaches to OPMDs and OSCC management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chadwick, Macdonald, Ali, Glogauer and Magalhaes.)

Background: Oral squamous cell carcinoma (OSCC) is a devastating disease that is usually associated with a dense associated inflammatory infiltrate. Characterizing tumor-associated inflammation is critical to understand the pathogenies of tumor development and progression. Methods: We have tested a protocol to analyze tissue and salivary immune cells and mediators of 37 patients with OSCC at different stages and compared to eight chronic periodontitis patients and 24 healthy controls. Tissue analysis was based on fluorescent immunohistochemistry (FIHC) and inflammatory mediators were analyzed using a Luminex-based 30-Plex panel. Immune cells were analyzed using multichannel flow cytometry including CD45, CD66b, CD3, CD4, CD8, CD25, CD56, CD68, CD138, PD-1, and PD-L1. Results: We show an increase in OSCC-associated inflammation characterized by increased pro-inflammatory cytokines including IL-6, IL-8, TNFα, and GMCSF and increased salivary immune cells. Conclusion: We described a new method to analyze salivary inflammatory markers that can be used in future studies to monitor disease progression and prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Laliberté, Ng, Eymael, Higgins, Ali, Kiss, Bradley and Magalhaes.)

Oral squamous cell carcinoma (OSCC) may be associated with precursor lesions known as oral potentially malignant disorders (OPMD). Few studies have reported on how OPMD diagnosis affects early detection and outcome of OSCC. We reviewed a large series of OSCC to determine the proportion that was associated with preceding OPMD and to compare the outcome of OSCC with or without precursor. Cases of oral-oropharyngeal carcinoma diagnosed between 2005 and 2015 were retrieved from the Ontario Cancer Registry (OCR) and matched to records of OPMD between 2001 and 2015 in two large oral pathology diagnostic services and the pathology databases of two hospitals with oral pathology services, to identify cases with precursor. Of 10,987 cancer cases, 378 (3.44%) had a preceding OPMD. Patients living in Central Ontario were more likely to have OPMD diagnosed before carcinoma than those in North Ontario (4.73% vs. 1.63%, P = 0.05). 329 of 5,257 cases of oral cancer were linked to a precursor, compared with 24 of 4,174 cases of oropharyngeal cancer (6.26% vs. 0.57%, P < 0.0001). Oral cancers with precursor were predominantly diagnosed at stage I (49.30%), compared with those without precursor, where stage IV disease predominated (41.28%). Sixty-nine of 309 (22.33%) patients with precursor-associated oral cancer have died of disease, compared with 1,551 of 4,656 (33.31%) patients without a precursor ( P = 0.02). We conclude that patients with OSCC associated with a precursor had significantly lower odds of dying from disease. The beneficial effect of precursor lesion diagnosis on outcome is related to a higher proportion of stage I disease. PREVENTION RELEVANCE: OSCC causes significant morbidity and mortality, especially if diagnosed at late stages. Precursor lesions to OSCC can be recognized by clinical examination. Our study shows that early diagnosis of OSCC at the precursor stage can improve the outcome of oral cancer., (©2021 American Association for Cancer Research.)

Multinucleated giant cells (MGCs) are prominent in foreign body granulomas, infectious and inflammatory processes, and auto-immune, neoplastic and genetic disorders, but the molecular determinants that specify the formation and function of these cells are not defined. Here, using tandem mass tag-mass spectrometry, we identified a differentially upregulated protein, C-type lectin domain family 10 member (herein denoted CD301, also known as CLEC10A), that was strongly upregulated in mouse RAW264.7 macrophages and primary murine macrophages undergoing interleukin (IL-4)-induced MGC formation. CD301 + MGCs were identified in biopsy specimens of human inflammatory lesions. Function-inhibiting CD301 antibodies or CRISPR/Cas9 deletion of the two mouse CD301 genes (Mgl1 and Mgl2) inhibited IL-4-induced binding of N-acetylgalactosamine-coated beads by 4-fold and reduced MGC formation by 2.3-fold ( P <0.05). IL-4-driven fusion and MGC formation were restored by re-expression of CD301 in the knockout cells. We conclude that in monocytes, IL-4 increases CD301 expression, which mediates intercellular adhesion and fusion processes that are required for the formation of MGCs.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Background: Dentists play an important role in the detection and diagnosis of oral diseases, including oral cancer and its precursor lesions. There are few comprehensive reviews in the recent literature that examine the scope and trends of oral disease diagnoses by dentists., Methods: The authors analyzed all accessions to the Toronto Oral Pathology Service at the Faculty of Dentistry at the University of Toronto in Toronto, Ontario, Canada, from 2005 through 2015 using a custom-built database. They used these data to calculate the temporal trends in the diagnoses of oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC)., Results: A total of 63,483 biopsy specimens were submitted primarily by dentists from 2005 through 2015. From these, 2,679 cases of OED and 828 OSCC were diagnosed. The authors' results show a 3.8-fold increase in the number of epithelial dysplasias and a 1.8-fold increase in mucosal carcinomas over the study period. The rate of increase of OED and OSCC was significantly higher than the rate of increase of total oral carcinomas diagnosed in the region, the population changes, and the number of dentists in the region., Conclusions and Practical Implications: Within the limitations of a study of a single large oral pathology biopsy service, the analysis of diagnoses shows that dentists are increasingly involved in the detection of oral mucosal carcinoma and precursor lesions. The dental community plays an important and increasing role in the detection of oral cancer and potentially malignant disorders. Increased awareness among oral health care and nonoral health care professionals may increase early detection of OSCC., (Copyright © 2019 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Objective: Evaluation of invasive hemodynamic parameters as prognostic markers of mortality in patients undergoing TAVR., Background: The value of invasive intraprocedural hemodynamic evaluation of patients undergoing transcatheter aortic valve replacement is unclear., Methods: Consecutive patients who underwent transfemoral TAVR and had complete prospectively collected intraprocedural invasive hemodynamic parameters were retrospectively analyzed. Patients with alternative access, planned general anesthesia, or baseline ≥moderate Tricuspid Regurgitation were excluded. Pre- and post-valve implant parameters included heart rate, systolic and diastolic blood pressures, cardiac output and index, pulmonary arterial systolic and diastolic pressures, transaortic pressure gradient and right atrial pressure. The primary end points were the association of the intraprocedural hemodynamic changes with all-cause mortality at 30days and 1year. Extensive Receiver Operating Characteristic analyses yielded dichotomized threshold of hemodynamic values in association with the binary outcome of mortality., Results: A total of 312 patients (52% male, mean age 83years) were evaluated. A significant association with 30-day and 1-year mortality was found between intraprocedural post-valve implant cardiac index <1.9 vs. ≥1.9L/min/m 2 (Log-ranked p=0.0286 and p=0.0432, respectively). Four subgroups with pre- and post-valve implant CI changes (L/min/m 2 ) were compared: [1] pre<1.9, stable&#95;post<1.9; [2] pre<1.9, improved&#95;post≥1.9; [3] pre≥1.9, stable&#95;post≥1.9; and [4] pre≥1.9, worsened&#95;post<1.9. Group 1 (lower CI with no post-valve improvement) had the worst survival, and Group 3 (higher CI and stable post-valve) had the best survival at 1-year follow-up (Log-ranked p=0.0089)., Conclusions: In patients with severe aortic stenosis undergoing TAVR, invasive monitoring can assess for hemodynamic prognostic markers of survival., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: The aim of this study is to summarize the outcomes of patients undergoing direct stenting (DS) with drug-eluting stents (DES) compared to those who underwent balloon predilatation., Background: DS has been associated with improved outcomes in the bare-metal stent era. Although DS with DES implantation has been increasingly adopted in clinical practice, its safety and effectiveness remain controversial., Methods: The search criteria identified 546 studies in the Medline/PubMed, Cochrane, and EMBASE databases from 2001 to July 2014. From these, seven studies totaling 10,900 patients were selected. Summarized estimates [odds ratio (OR) and 95% confidence intervals] were obtained using a random-effects model. The primary outcomes were a composite of major adverse cardiac events (MACE), including all-cause death, myocardial infarction (MI), and repeat revascularization. The secondary outcomes included a composite of death and MI and the rates of target lesion revascularization (TLR)., Results: Overall, 4101 (38%) and 6799 (62%) patients underwent DS with DES and balloon pre-dilatation, respectively. DS with DES reduced the likelihood of MACE (OR: 0.81 [0.71-0.93]). Additionally, DS with DES was associated with reduced rates of death/MI (OR: 0.76 [0.62-0.92]), and TLR (OR: 0.66 [0.44-0.98])., Conclusions: DS with DES is safe and may be associated with better outcomes in selected patients. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Oral squamous cell carcinoma (OSCC) is extremely rare in patients younger than 20 years of age. We present here a case of OSCC of the maxillary alveolar ridge in an otherwise healthy 8-year-old patient. The clinicohistologic presentation was not typical for mucosal SCC, and the possibility of an intrabony origin from the odontogenic epithelium was considered. The patient was treated with surgical resection, and treatment decisions were made with consideration of the need for eradication of tumor as well as tissue preservation to allow normal growth and development. A review of the literature indicated a preponderance of gingival-alveolar ridge as the site of OSCC in children with no known genetic predisposition to cancer. More studies of this rare subset of OSCC will help understand the underlying biology and guide treatment decisions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: The radiation exposure resulting from cardiovascular procedures may increase the risk of cancer, and/or cause skin injury. Whether the novel cardiovascular automated radiation reduction X-ray system (CARS) can help reduce the patient radiation dose in daily clinical practice remains unknown. The aim of this study was to evaluate the reduction in patient radiation dose with the use of CARS in the cardiac catheterisation laboratory (CCL)., Methods and Results: This study retrospectively analysed 1,403 consecutives patients who underwent a cardiac catheterisation with coronary angiography (CA) and/or a percutaneous coronary intervention (PCI) in the Brest University Hospital over the course of one year. Patient radiation doses (dose area product and air kerma) were collected and compared between the CCL with (new CCL) and without (control CCL) CARS. Additionally, the patient radiation doses according to femoral versus radial access, procedural complexity and body mass index were compared. The radiation lesion position on the skin was assessed by automatically optimising the X-ray source to image distance (SID) and subsequently generating a radiation Dose-Map for those procedures exceeding 3 Gray of exposure. Overall, 447 patients underwent procedures in the control CCL and 956 in the new CCL. Baseline patient and procedural characteristics were similar between the two groups, with the exception of male gender and primary PCI, which were more prevalent in the new CCL group. Compared to the control CCL, the utilisation of the CARS in the new CCL resulted in a reduction of dose area product by 46% for CA, 56% for PCI alone and 54% for CA and PCI during the same procedure. Of note, radial access generated a higher radiation dose than femoral access (p<0.001). In this study, seven patients had an air kerma exceeding 3 Gray; however, only one patient had a skin dose greater than 3 Gray., Conclusions: The utilisation of the CARS resulted in a significant reduction in patient radiation doses compared to the control equipment. A real-time Dose-Map may help the operator change the projection during complex procedures to reduce the patient skin dose.

Background: There is no clear consensus in regard to the optimal anesthesia utilization during transcatheter aortic valve replacement (TAVR). The aim was to compare outcomes of transfemoral (TF) TAVR under monitored anesthesia care (MAC) vs. general anesthesia (GA) and evaluate the rates and causes of intra-procedural MAC failure., Methods: All consecutive patients who underwent TF TAVR from April 2007 through March 2015 were retrospectively analyzed and dichotomized into two groups: TAVR under MAC vs. GA. The main endpoints of the study included 30-day and 1-year mortality, the rates and reasons for failure of MAC, in-hospital clinical safety outcomes, and post-procedural hospital and intensive care unit length-of-stays., Results: A total of 533 patients (51% male, mean-age 83years) underwent TF TAVR under MAC (n=467) or GA (n=66). Fifty-six patients (12%) in the MAC group required conversion to GA. The MAC group had significantly shorter post-procedural hospital (6.0 vs. 7.9, p=0.023) and numerically shorter ICU (2.4 vs. 2.8, p=0.355) mean length-of-stays in days. The clinical safety outcomes were similar in both groups. Kaplan-Meier unadjusted cumulative in-hospital and 30-day mortality rates were higher in the GA group but similar in both groups at 1-year., Conclusions: TF TAVR under MAC is feasible and safe, results in shorter hospital stays, can be performed in the majority of cases, and should be utilized as the default strategy. Trans-esophageal echocardiography utilization during TAVR with MAC is safe and feasible. The most common cause for conversion of MAC to GA is cardiac instability and hypotension. The complete heart team should be available at all times in case the need arises for a rapid conversion to GA., (Copyright © 2016. Published by Elsevier Inc.)

Background: The prevalence of concomitant significant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) ranges from 2% to 33%. The impact of significant MR on post-TAVR outcomes remains controversial., Methods: The data from a cohort of patients with symptomatic severe AS undergoing TAVR at out institution were retrospectively analyzed. The last transthoracic echocardiogram (TTE) before the index TAVR procedure was selected as the baseline assessment of the degree of MR. The total study cohort (N = 589) was divided into 2 groups: significant ≥moderate MR (n = 68) versus nonsignificant

Aims: Vessel remodelling is commonly observed in coronary atherosclerosis, but factors influencing remodelling, such as plaque lipid content, remain poorly described., Methods and Results: Remodelling index (RI) was calculated as the ratio of lesion to proximal and distal references external membrane area and was categorized as follows: positive (PR; RI > 1.05), intermediate (IR; RI 0.95-1.05), and negative remodelling (NR; RI < 0.95). RI was studied by near-infrared spectroscopy (NIRS) as a function of lipid content metrics, including the maximal 4 mm lipid core burden index of the segment (maxLCBI4 mm) and intravascular ultrasound (IVUS) lesion plaque burden (PB). The authors further stratified the analysis according to obstructive (≥50%) and non-obstructive (<50%) lesions using quantitative coronary angiography. Receiver-operating characteristic curves were performed to describe the maxLCBI4 mm level associated with PR. From May 2012 to November 2014, 100 de novo lesions from 67 patients underwent simultaneous NIRS-IVUS. PR was found in 28% of the lesions. There was a positive linear correlation between RI and maxLCBI4 mm (ρ = 0.58; P < 0.001). Although PR lesions had a larger PB than NR or IR (P < 0.001), the correlation of RI with maxLCBI4 mm was stronger compared with plaque volume (ρ = 0.18; P = 0.07) and with per cent PB (ρ = 0.41; P < 0.001). This relationship remained significant for obstructive (ρ = 0.72; P < 0.001) and non-obstructive lesions (ρ = 0.48; P < 0.001). By receiver-operating characteristic curve analysis, values of maxLCBI4 mm ≥ 439 were predictive for PR (area under the curve = 0.79, 95% confidence interval: 0.69-0.89)., Conclusion: In vivo coronary lesion remodelling is positively correlated with lipid plaque content assessed by NIRS rather than simply PB. Thus, the use of NIRS can potentially aid in further stratifying vulnerable lesions., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Aims: The objective of this study was to describe and evaluate the adjunctive technique of Angio-Seal (AS) use to augment the dual Perclose ProGlide (PP) in achieving haemostasis in patients undergoing transfemoral percutaneous transcatheter aortic valve replacement (TAVR)., Methods and Results: All patients who underwent TAVR from May 2007 to January 2015 via a planned transfemoral percutaneous approach with a dual PP pre-close strategy were retrospectively analysed. This cohort was divided into two groups: dual PP versus dual PP with adjunctive AS (PP+AS) use based on the specific status of intraprocedural haemostasis. The baseline and procedural characteristics and in-hospital outcomes were prospectively collected and retrospectively compared. Overall, a total of 387 consecutive patients (55% male, mean age 83 years) with dual PP (n=179) vs. dual PP+AS (n=208) were evaluated. There were no statistically significant differences between the dual PP vs. dual PP+AS groups with regard to the in-hospital Valve Academic Research Consortium-2 (VARC-2) primary endpoints of major vascular complications (8.0% vs. 6.6%, p=0.592), minor vascular complications (18.4% vs. 13.7%, p=0.218), life-threatening or disabling bleeding (5.1% vs. 3.0%, p=0.291), major bleeding (1.7% vs. 1.5%, p=1.000), and minor bleeding (14.4% vs. 10.6%, p=0.271)., Conclusions: The adjunctive Angio-Seal technique to augment the dual PP pre-close strategy for patients undergoing percutaneous femoral closure following TAVR is feasible and safe and may be considered as a bail-out or an alternative strategy when the dual PP closure technique fails to obtain complete haemostasis.

The incidence of aortic regurgitation (AR) after transcatheter aortic valve replacement (TAVR) in a self-expanding and a balloon-expandable system is controversial. This study aimed to examine the incidence and severity of post-TAVR AR with the CoreValve (CV) versus the Edwards XT Valve (XT). Baseline, procedural, and postprocedural inhospital outcomes were compared. The primary end point was the incidence of post-TAVR AR of any severity, assessed with a transthoracic echocardiogram, in the CV versus XT groups. A multivariate logistic regression analysis was completed to evaluate for correlates of the primary end point. The secondary end points included the change in severity of AR at 30-day and 1-year follow-up. A total of 223 consecutive patients (53% men, mean age 82 years) who had transfemoral TAVR with either a CV (n = 119) or XT (n = 104) were evaluated. The rates of post-TAVR AR in the groups were similar, and there was no evidence of more-than-moderate AR in either group. There were significant differences in the rates of intraprocedural balloon postdilation with the CV (17.1%) versus XT valve (5.8%; p = 0.009) and in the rates of intraprocedural implantation of a second valve-in-valve prosthesis with the CV (9.9%) versus XT valve (2.2%; p = 0.036). There were no significant differences in inhospital safety outcomes between the 2 groups. In conclusion, the incidence of post-TAVR AR is similar between the CV and the XT valve when performed by experienced operators using optimal intraprocedural strategies, as deemed appropriate, to mitigate the severity of AR., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Currently, percutaneous endovascular intervention is considered a first line of therapy for treating patients with critical limb ischemia. As the result of remarkable development of techniques and technologies, percutaneous endovascular intervention has led to rates of limb salvage comparable to those achieved with bypass surgery, with fewer complications, even in the presence of lower rates of long-term patency. Currently, interventionalists have a multiplicity of access routes including smaller arteries, with both antegrade and retrograde approaches. Therefore, the choice of the optimal access site has become an integral part of the success of the percutaneous intervention. By understanding the technical aspects, as well as the advantages and limitations of each approach, the interventionalists can improve clinical outcomes in patients with severe peripheral arterial disease. This article reviews the access routes in critical limb ischemia, their advantages and disadvantages, and the clinical outcomes of each., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The impact of the specific etiology of mitral regurgitation (MR) on outcomes in the transcatheter aortic valve replacement (TAVR) population is unknown. This study aimed to evaluate the longitudinal changes in functional versus organic MR after TAVR in addition to their impact on survival. Consecutive patients who underwent TAVR from May 2007 to May 2015 who had baseline significant (moderate or greater) MR were included. Transthoracic echocardiography was used to evaluate the cohort at baseline, post-procedure, 30-day, 6-month, and 1-year follow-up. The primary outcomes included mortality at 30 days and 1 year. Longitudinal, mixed-model regression analyses were performed to assess the differences in the magnitude of longitudinal changes of MR, left ventricular (LV) ejection fraction, and New York Heart Association functional class. Seventy patients (44% men, mean 83 years) with moderate or greater MR at baseline (30 functional vs 40 organic) were included, with the functional group having a statistically significant mean younger age and higher rates of previous coronary artery bypass grafting. Kaplan-Meier cumulative mortality rates were similar: 30 days (10% vs 17.5%, unadjusted log-ranked p = 0.413) and 1 year (29.4% vs 23.2%, unadjusted log-ranked p = 0.746) in the functional versus organic MR groups, respectively. There were greater degrees of short- and long-term improvement in MR severity (slope difference p = 0.0008), LV ejection fraction (slope difference p = 0.0009), and New York Heart Association class (slope difference p = 0.0054) in the functional versus organic group. In conclusion, patients with significant functional versus organic MR who underwent TAVR have similar short- and long-term survival; nevertheless, those with a functional origin are more likely to have significant improvements in MR severity, LV-positive remodeling, and functional class. These findings may help strategize therapies for MR in patients with combined aortic and mitral valve disease who are undergoing TAVR., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Transcatheter aortic valve replacement (TAVR) is the current standard for nonoperable and high-risk surgical patients with aortic stenosis, including those of advanced age. However, the clinical profiles, procedural characteristics, and outcomes of nonagenarians undergoing TAVR have not been thoroughly reported., Methods: A total of 654 patients (n = 107 >90 years old and n = 547 <90 years) with severe aortic stenosis undergoing TAVR were included in this analysis. Baseline characteristics, procedural variables, and in-hospital outcomes and complications at 30 days and 12 months were analyzed., Results: Overall, of the patients included, 46% were high risk and 53% inoperable. Although nonagenarians had a higher Society of Thoracic Surgeons score of 9.2 ± 4 (12.1 ± 4 vs 8.6 ± 4, P < .001), other factors were considerably lower in this group: diabetes (22% vs 36%, P = .008), hyperlipidemia (65% vs 83%, P < .001), prior coronary artery bypass (13% vs 39%, P < .001), and mean body mass index (24.5 ± 5 vs 28.1 ± 7 kg/m(2), P < .001). The correlates for 1-year mortality in nonagenarians were as follows: ≥moderate aortic insufficiency post-TAVR (hazard ratio [HR] 5.07, 95% CI 1.17-22, P = .03), pacemaker implantation after TAVR (HR 6.87, 95% CI 2.32-20.3, P = .001), and peripheral vascular disease (HR 2.35, 95% CI 1.03-5.38, P = .042). Mortality at 30 days (12.1% vs 7.1%, P = .07) and at 1 year (25% vs 21%, P = .35) was similar between groups., Conclusion: Nonagenarians undergoing TAVR had a healthier clinical profile compared with younger patients. Age alone should not be a discriminatory factor when screening elderly patients with aortic stenosis because even the nonagenarians are doing well when compared with the younger elderly population. Transcatheter aortic valve replacement remains a viable option for the treatment of severe symptomatic aortic stenosis for the elderly regardless of their age., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: We evaluate the prevalence of complications and failure rates between the most commonly used "active" anchoring vascular closure device (VCD), AngioSeal™ and the "passive" anchoring VCD, Mynx™, in all-comers undergoing percutaneous coronary intervention (PCI)., Methods: A total of 4,074 patients between 2008 and 2014, representing an era when both devices were available, were included. Thirty-two percent were acute coronary syndromes (37% STEMI). VCD choice was at the operator's discretion and included AngioSeal (n = 2,910) or Mynx (1,164). Cardiogenic shock or patients receiving intra-aortic balloon pumps were excluded. Safety was assessed by vascular complications defined as either vascular injury (perforation, dissection, acute limb ischemia, arteriovenous fistula, pseudoaneurysm with thrombin injection, or surgical repair) or access-site bleed (hemoglobin droP >3 g/dL requiring transfusion, retroperitoneal bleed, or hematoma >5 cm, or the composite of both. Efficacy was evaluated by device failure and defined as inability to achieve immediate hemostasis or use of additional hemostatic mechanisms. Outcomes at 30-days were evaluated., Results: Groups (AngioSeal vs Mynx) were fairly balanced with regards to bleeding risk factors of gender (male, 65% vs 66%), body mass index (30 ± 6 vs 30 ± 7), heart failure class III/IV (5% vs 6%), chronic kidney disease (15% vs 17%), use of glycoprotein IIb/IIIa inhibitor (5% vs 4%), or bivalirudin (86% vs 88%), all P >0.5. The AngioSeal group was slightly younger (64 ± 12 vs 65 ± 12, P < 0.001) with less peripheral arterial disease (11.3% vs 13.9%, P = 0.03), and increased 7F sheath use compared with Mynx (59% vs 22%, P < 0.001). Safety and efficacy outcomes were similar between groups., Conclusions: AngioSeal and Mynx appear to be equally safe and efficacious VCDs following PCI. The passive anchoring system may prove desirable as no intra-arterial anchor remains upon device removal., (© 2015, Wiley Periodicals, Inc.)

Objectives: We sought to identify if baseline characteristic differences in patients who receive a 23 mm vs. 26 mm valve impact clinical outcomes., Background: Transcatheter aortic valve replacement (TAVR) is currently an approved therapy for patients with severe aortic stenosis who are considered inoperable or are at high risk., Methods: We retrospectively examined baseline characteristics and outcomes of patients receiving a 23 mm (n = 132) vs. 26 mm valve (n = 81) via the transfemoral approach., Results: Gender (P < 0.01), previous coronary artery bypass surgery (P < 0.01), history of atrial fibrillation (P = 0.04), and mean Society of Thoracic Surgeons (STS) score (P < 0.01) were significantly different between groups. There were no significant differences in the rates of minor/major vascular complications (2.2 vs. 3.7%, P = 0.68 and 13.0 vs. 12.3%, P = 0.89, respectively). Bleeding complications were also comparable (major bleed 2.3 vs. 1%, P >0.99, minor bleed 19.0 vs. 22.0%, P = 0.67 and life threatening bleed 7.0 vs. 5.0%, P = 0.77). In-hospital death (6.0 vs. 5.0%, P >0.99), 30-day all-cause death (7.6 vs. 6.2%, P = 0.69), and all-cause death at 1 year (17.4 vs. 25.9%, P = 0.13) were also similar between groups. Gender, valve size, previous coronary bypass surgery and atrial fibrillation were not independently associated with mortality; however, on multivariate analysis STS score was (HR 1.11; 95% CI 1.02-1.19; P = 0.01)., Conclusion: Patients undergoing TAVR with 23 and 26 mm valves have similar clinical outcomes despite significant differences in baseline characteristics. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Objective: To compare the clinical outcomes of patients undergoing percutaneous intervention for stent thrombosis (ST) or saphenous vein graft (SVG) occlusion., Background: Patients presenting with ST or SVG occlusion are at increased risk of adverse outcomes. There is limited literature comparing the outcome of such patients., Methods: A cohort of 415 consecutive patients presenting to the MedStar Washington Hospital Center undergoing percutaneous coronary intervention (PCI) for an acute coronary syndrome secondary to ST (n=136) or SVG occlusion (n=279) was studied. The SVG group was subdivided into patients who underwent PCI in the occluded SVG (SVG-PCI: n=75) or in the subtended native coronary artery (NC-PCI: n=204). The analyzed clinical parameters were in-hospital complications as well as 30-day and 1-year major adverse cardiac events (MACE). MACE was defined as all-cause mortality, Q-wave myocardial infarction, or target vessel revascularization., Results: The rates of death, major bleeding, and length of hospital stay were significantly different between the ST and NC-PCI groups. The SVG-PCI group had a shorter hospital stay. The 30-day MACE rate was significantly different in the ST and NC-PCI groups (18.9% vs. 7.5%; risk ratio=0.40, 95% CI=0.20-0.81, p=0.03) but not in the ST and SVG-PCI groups (18.9% vs. 15.1%; p=0.55, risk ratio=0.80, 95% CI=0.38-1.68). There were no differences in the 1-year MACE rate., Conclusions: As compared to patients undergoing NC-PCI, patients with ST have greater rates of in-hospital mortality and major bleeding as well as 30-day MACE rate. The 1-year MACE rate is similar in patients with ST and SVG occlusion who undergo PCI., (Copyright © 2015. Published by Elsevier Inc.)

Neutrophils have recently been shown to promote invasion and correlate with a poor prognosis in different cancers, including head and neck squamous cell carcinomas. In this study, we analyze the effects of neutrophils in the invasion of oral squamous cell carcinoma (OSCC) using a combination of conditioned media, direct and indirect coculture of human peripheral blood neutrophils, and UMSCC47 cells (OSCC cell line). Invasion and matrix degradation were determined using a modified in vitro invasion assay and an invadopodia assay, respectively. UMSCC47 and neutrophil cocultures or conditioned media from cocultures increased UMSCC47 invasion, invadopodia formation, and matrix degradation. Further analysis revealed an increase in TNFα and IL8 in supernatants of cocultures compared with neutrophil or UMSCC47 cultures alone and that inhibition of TNFα and IL8 significantly decreased OSCC invasion. Our results show that neutrophils increase the invasiveness of OSCC through the activation of invadopodia and matrix degradation, suggesting a paracrine activation loop between the two cells. Importantly, the presence of neutrophils in the oral environment may modulate the clinical behavior of OSCC., (©2015 American Association for Cancer Research.)

Aims: Our aim was to compare the outcomes of complete revascularisation (CR) and incomplete revascularisation (IR) in multivessel coronary artery disease (CAD), with and without intravascular ultrasound (IVUS) guidance, in the drug-eluting stent (DES) era., Methods and Results: Overall, 2,132 consecutive patients with multivessel CAD, defined as at least two epicardial vessels with >70% stenosis, had at least one DES implant. Chronic total occlusions were not analysed. Successful treatment of epicardial vessels and significant branches was termed CR; otherwise, treatment was defined as IR. CR and IR were further categorised according to the use of IVUS. The primary outcome was death or Q-wave myocardial infarction (QWMI). Secondary outcomes included the rates of non-QWMI and repeat revascularisation, the latter assessed as either target vessel revascularisation (TVR) or target lesion revascularisation (TLR) at one year. CR was associated with lower rates of death/QWMI (HR 0.66 [0.4-0.9]; p=0.048) and non-QWMI at one year (1.1% vs. 2.6%; p=0.017). Completeness of revascularisation was not independently associated with repeat intervention, but rates of both TVR (89% vs. 93%; p<0.001) and TLR (91% vs. 95%; p<0.001) were higher with CR than IR. IVUS decreased the rates of TLR irrespective of completeness of revascularisation (p-interaction=0.75)., Conclusions: CR in selected patients gives better outcomes than IR in multivessel CAD at one year. IVUS guidance can further improve results by reducing rates of repeat intervention irrespective of completeness of revascularisation.

Left-sided cardiac remodeling in patients with severe aortic stenosis (AS) was associated with improved outcome; however, there are scarce data on remodeling process after transcatheter aortic valve implantation (TAVI). We sought to describe the remodeling process in patients with severe AS who underwent TAVI. Echocardiographic data were systematically collected at baseline, 30 days, 6 months, and 1 year, from a cohort of 333 patients who underwent TAVI. Patients were categorized according to left ventricular mass index (LVMi) and relative wall thickness (RWT) to the following geometries: (1) normal; (2) concentric remodeling; (3) concentric hypertrophy; and (4) eccentric hypertrophy. Reverse remodeling (partial or complete) was defined as normalization of LVMi and/or RWT and adverse remodeling as an increase in LVMi and/or RWT. The longitudinal change in LVMi and left atrial diameter index (LADi) was assessed using mixed models. Reverse LV remodeling at 1-year was observed in 24% of patients with available echo at follow-up, whereas 17% of patients had adverse remodeling at 1-year follow-up. This was especially noted in patients with normal geometry at baseline. Interestingly, LV reverse remodeling was not accompanied by a reduction in left atrial diameter. In conclusion, TAVI reverse ventricular remodeling and LV hypertrophy induced by aortic stenosis; however, this reversal is incomplete in most patients at 1-year and not followed by change in left atrial dimensions. Whether this favorable remodeling may impact clinical outcome needs to be further elucidated., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Mortality after transcatheter aortic valve implantation (TAVI) has been reported to range up to 3 years. However, long-term mortality remains underexplored. The aims of this study were to determine long-term mortality in patients who undergo TAVI and to identify correlates of long-term death. From a single institution's prospectively collected TAVI database, all patients who underwent TAVI with a maximum follow-up duration of 5 years were analyzed. The population was analyzed on the basis of access route (transapical TAVI or transfemoral TAVI). Cox regression and Kaplan-Meier survival analysis were conducted. A total of 511 patients who underwent TAVI were included in the analysis (transapical TAVI n = 115, transfemoral TAVI n = 396). The mean Society of Thoracic Surgeons score was 9.6 ± 4. Mortality at 30 days (18% vs 6%, p <0.001) and 1 year (32% vs 21%, p <0.01) was significantly increased in the transapical TAVI group. Long-term survival probability was <50% for the 2 approaches (log-rank p = 0.33). Vascular complications (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.38 to 3.33, p = 0.001), more than mild aortic insufficiency (HR 1.81, 95% CI 1.15 to 2.83, p = 0.01), atrial fibrillation (HR 1.87, 95% CI 1.36 to 2.57, p <0.001), and in-hospital stroke (HR 2.35, 95% CI 1.39 to 4.00, p = 0.002) were independently associated with long-term death. The survival probability of patients at high surgical risk versus those who were inoperable was similar in the long term (log-rank p = 0.53). In conclusion, the overall long-term survival of patients with aortic stenosis who were approved to undergo TAVI was <50% irrespective of access method. Strategies geared toward reducing in-hospital stroke, vascular complications, and aortic regurgitation are still needed, as these variables are correlates of long-term mortality., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Near-infrared spectroscopy is an intracoronary imaging modality that has been validated in preclinical and clinical studies to help quantify the lipid content of the coronary plaque and provide information regarding its vulnerability. It has the potential to develop into a valuable tool for the risk stratification of a vulnerable plaque and, furthermore, a vulnerable patient. In addition, in the future this technology may help in the development of novel therapies that impact vascular biology., (Copyright © 2015. Published by Elsevier Inc.)

Risk assessment for transcatheter aortic valve replacement (TAVR) patients is challenging, and surgical scores do not optimally correlate with outcome. The aim of this study was to assess the correlation between serum albumin and survival of patients with symptomatic severe aortic stenosis undergoing TAVR. Patients with severe aortic stenosis who underwent TAVR were categorized into 2 groups according to low and normal preprocedural serum albumin (<3.5 and ≥3.5 g/dl, respectively). The all-cause mortality rates at hospital discharge, at 30-day and 1-year follow-up were compared across the groups. Additionally, a Cox proportional-hazards model was generated to assess the independent effect of serum albumin at 1-year follow-up. Among 567 consecutive patients who underwent TAVR, 476 (84%) had documented preprocedural serum albumin measurements. Of these, 50% had low serum albumin levels, and 50% had normal serum albumin levels. Baseline and procedural characteristics, including age, gender, and transapical access, were similar among the groups. Prevalence of left ventricular ejection fraction<40% was higher in patients with low albumin (29% vs 20%, p=0.02), and risk assessment according to Society of Thoracic Surgeons score tended to be higher in the low-albumin group (10±4.7 vs 9.4±4.4, p=0.09). Patients presenting with low albumin had higher in-hospital mortality (11% vs 5%), as well as at 30-day (12% vs 6%, p=0.01) and 1-year (29% vs 19%, p=0.02) follow-up. Serum albumin was independently associated with 1-year mortality (adjusted hazard ratio per 0.1 g/dl decrease 1.64, 95% confidence interval 2.50 to 1.75, p=0.02), along with body mass index<20 kg/m2 (hazard ratio 1.89, 95% confidence interval 3.33 to 1.75, p=0.03). In conclusion, preprocedural serum albumin level and low body mass index are independently associated with mortality in patients who undergo TAVR. Patients with severe aortic stenosis and low albumin levels should undergo careful evaluation before and after TAVR., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Studies have linked on-treatment platelet reactivity (PR) to adverse clinical outcomes. Because new P2Y12 inhibitors (prasugrel and ticagrelor) have been predominantly tested against clopidogrel, data on pharmacodynamic comparisons between these 2 drugs are scarce. We compared ticagrelor with prasugrel in a network meta-analysis. PubMed, Cochrane, and EMBASE were searched for studies assessing PR in patients with coronary artery disease treated with ticagrelor or prasugrel. All studies using prasugrel and/or ticagrelor providing platelet function measurement data using VerifyNow P2Y12 reaction units (PRUs), platelet reactivity index (PRI) vasodilator-stimulated phosphoprotein phosphorylation, or maximal platelet aggregation (MPA) by light transmission aggregometry were considered eligible. Mixed treatment comparison models directly compared ticagrelor and prasugrel and indirectly compared them using clopidogrel as a comparator with data presented as mean difference (95% confidence interval). Data were extracted from 29 studies, including 5,395 patients. Compared with clopidogrel 75 mg, both prasugrel 10 mg and ticagrelor 90 mg twice daily were associated with lower PRU (mean difference -117 [-134.1, -100.5] and -159.7 [-182.6, -136.6], respectively), a lower PRI (-24.2 [-28.2, -20.3] and -33.6 [-39.9, -27.6], respectively), and lower MPA (-11.8 [-17, -6.3] and -20.7 [-28.5, -12.8], respectively). Similar results were obtained with clopidogrel 150 mg. Ticagrelor 90 mg twice daily was associated with lower PRU (-42.5 [-62.9, -21.9]), lower PRI (-9.3 [-15.6, -3.5]), and lower MPA (-8.9 [-16.4, -1.2]) compared with prasugrel 10 mg. In conclusion, our meta-analysis suggests that ticagrelor achieved significantly lower on-treatment PR compared with prasugrel, with both being superior to clopidogrel standard or high dose., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Adenosquamous carcinomas of the head and neck (ADSCs) are rare locally aggressive malignancies characterized by the presence of two distinctive components, a squamous cell carcinoma and an adenocarcinoma. The immunophenotype of the glandular component of ADSCs has only been rarely studied but has been reported as being positive for keratin 7 (CK7) and carcinoembryonic antigen (CEA) and negative for keratin 20 (CK20). Herein, we report a case of an ADSCs of the hypopharynx composed of a superficial squamous cell carcinoma and an adenocarcinoma with an intestinal phenotype. The patient was a 62 year-old male with a T2 N0 M0 squamous cell carcinoma (SCC) of uvula and palate and a T1 N0 M0 of right hypopharynx. The ADSCs of the hypopharynx was composed of a minimally invasive SCC and an adenocarcinoma with tubulo-glandular and cribriform architecture. The neoplastic glands were positive for CK7, CK20, CDX2, CEA and Villin. The patient underwent radiotherapy to both tumors and remains well with no evidence of recurrent disease 19 months after treatment. To the best of our knowledge, this is the first report of an ADSCs of the head and neck with an intestinal phenotype in its glandular component.

Objective: This study aimed to report the outcomes of African Americans (AAs) in the US undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS)., Background: Compared to Caucasians, AAs are reported to have poorer outcomes from most cardiovascular diseases, including high complication rates after surgical aortic valve replacement. The outcomes of AAs undergoing TAVR are not well established., Methods: Consecutive patients who underwent TAVR were included in this analysis. Patients' baseline characteristics, procedural data, in-hospital- and long-term outcomes were recorded and a comparison was performed between the AA and Caucasian cohorts., Results: In a cohort of 469 consecutive patients, 51 (10.8%) were AA and 345 (74.5%) were Caucasian. The remaining patients (n = 73; 15.3%) self-reported their race as "unknown" or were from other races. Most baseline characteristics were similar between the two groups except for less men (33.3 vs. 50.1%; P = 0.016), a lower mean left ventricular ejection fraction (48.85 ± 16.35 vs. 53.24 ± 13.41%; P = 0.04) and lower rates of atrial fibrillation in AAs (15.7 vs.45.4%; P < 0.001). TAVR procedures in AAs were less frequently performed as part of a clinical trial (60.8 vs. 76.8%; P = 0.014). Most procedural and periprocedural outcome parameters were similar save for a higher rate of hemodynamic instability and postoperative need for intubation in AAs (10.4 vs. 2.5%; P = 0.018 and 29.4 vs. 16.9%; P = 0.03, respectively). This did not translate into a difference in mortality between AAs and Caucasians (30-day mortality 9.8 vs. 9.9%; P = 0.99; 1-year mortality 19.6 vs. 24.3%; P = 0.458, respectively)., Conclusion: Unlike with other cardiovascular interventions, this study demonstrates that AA patients referred for TAVR shared similar risks and outcomes when compared to a Caucasian population., (© 2014 Wiley Periodicals, Inc.)

Baseline anemia is associated with transfusions and increased risk of mortality in patients who underwent cardiac surgery and percutaneous coronary intervention. The impact of blood transfusions in anemic patients who underwent transcatheter aortic valve implantation (TAVI) remains unclear. All patients who underwent transfemoral TAVI at our institution were retrospectively included. We determined the effect of blood transfusions on short- and long-term mortality and its interaction with baseline hemoglobin levels and bleeding complications. Additionally, we evaluated baseline hemoglobin effect on mortality. A total of 332 patients were included. All patients (99%) except 2 (1%) met the definition for anemia. Of the 332 patients, 124 (37%) received a blood transfusion and 208 (63%) did not. Blood transfusions were associated with increased in-hospital (p <0.001), 30-day (p <0.001), and 1-year (28% vs 13%, p = 0.001) mortality; however, after a landmark analysis, the effect of blood transfusion on mortality was only seen within 30 days of the procedure (p = 0.001). The increased risk of mortality associated with blood transfusion was present after multivariate adjustment at 30 days (hazard ratio 3.59 [1.04 to 12.4]; p = 0.04). Major vascular complications were a correlate for short- and long-term death. In contrast, baseline hemoglobin level and bleeding complications were not independently associated with mortality. The p value for interaction was not significant between transfusion and hemoglobin level and for transfusion and bleeding complication and transfusion and major vascular complication. In conclusion, the presence of anemia in patients who underwent TAVI does not affect mortality. Transfusion is a correlate of all-cause mortality in this patient population and should be used with caution., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to investigate the long-term safety and efficacy of everolimus-eluting stents (EES) compared with other limus-eluting stents and bare metal stents (BMS) in ACS patients., Background: There have been concerns about the long-term safety of drug-eluting stents in the setting of acute coronary syndrome., Methods: The study cohort included 1,612 patients presenting with acute coronary syndrome who underwent BMS, SES, E-ZES, or EES implantation. End points included probable or definite stent thrombosis and major adverse cardiovascular events (MACE), defined as a composite of all-cause death, Q-wave myocardial infarction, and target lesion revascularization up to 3 years., Results: The overall MACE rates were significantly higher for both BMS and SES, but not E-ZES, when compared with EES (EES vs. BMS: HR 2.68, 95% CI 1.91-3.78, P <0.001; EES vs. SES: HR 1.75, 95% CI 1.24-2.47, P = 0.001 and EES vs., E-Zes: HR 1.08, 95% CI 0.65-1.77, P = 0.72). Stent thrombosis rates were similar for EES, E-ZES, and BMS but higher for SES throughout the 3-year follow-up (EES vs. BMS: HR 1.02, 95% CI: 0.31-3.35, P = 0.973; EES vs. SES: HR 4.90, 95% CI: 1.75-13.69, P = 0.002 and EES vs., E-Zes: HR 1.63, 95% CI 0.37-7.31, P = 0.449)., Conclusions: There was an improvement in the long-term outcome for MACE with EES when compared to earlier-generation stents, but this was comparable with the 2nd-generation E-ZES. There was no additional risk of early or late stent thrombosis in EES when compared with BMS., (© 2014 Wiley Periodicals, Inc.)

Background: Clinical presentation of bare metal stent in-stent restenosis (ISR) in patients undergoing target lesion revascularization is well characterized and negatively affects on outcomes, whereas the presentation and outcomes of first- and second-generation drug-eluting stents (DESs) remains under-reported., Methods and Results: The study included 909 patients (1077 ISR lesions) distributed as follows: bare metal stent (n=388), first-generation DES (n=425), and second-generation DES (n=96), categorized into acute coronary syndrome (ACS) or non-ACS presentation mode at the time of first target lesion revascularization. ACS was further classified as myocardial infarction (MI) and unstable angina. For bare metal stent, first-generation DES and second-generation DES, ACS was the clinical presentation in 67.8%, 71.0%, and 66.7% of patients, respectively (P=0.470), whereas MI occurred in 10.6%, 10.1%, and 5.2% of patients, respectively (P=0.273). The correlates for MI as ISR presentation were current smokers (odds ratio, 3.02; 95% confidence interval [CI], 1.78-5.13; P<0.001), and chronic renal failure (odds ratio, 2.73; 95% CI, 1.60-4.70; P<0.001), with a protective trend for the second-generation DES ISR (odds ratio, 0.35; 95% CI, 0.12-1.03; P=0.060). ACS presentations had an independent effect on major adverse cardiac events (death, MI, and re-target lesion revascularization) at 6 months (MI versus non-ACS: adjusted hazard ratio, 4.06; 95% CI, 1.84-8.94; P<0.001; unstable angina versus non-ACS: adjusted hazard ratio, 1.98; 95% CI, 1.01-3.87; P=0.046)., Conclusions: ISR clinical presentation is similar irrespective of stent type. MI as ISR presentation seems to be associated with patient and not device-related factors. ACS as ISR presentation has an independent effect on major adverse cardiac events, suggesting that ISR remains a hazard and should be minimized., (© 2014 American Heart Association, Inc.)

Objectives: This study aims to establish if transfer distance impacts the outcome of ST-elevation myocardial infarction (STEMI) patients transferred to a percutaneous coronary intervention (PCI)., Background: Regional emergency care systems were designed to decrease delays in reperfusion of patients but the effect of transfer distance on outcome is less established., Methods: We compare the characteristics and outcomes of STEMI patients transferred from a distance >25 miles (GT25) to those transferred from distances ≤25 miles (LT25) by utilizing data from a regional STEMI care network in the greater Washington DC area., Results: Within the transferred patients (n=1065), 609 patients (57%) were transferred from GT25 (median distance 36 miles), while 456 (43%) were transferred from LT25 (median distance 13 miles). Most of the baseline characteristics between the groups were similar. Door-to-balloon (DTB) was defined as the time elapsed from the presentation to the center without PCI capability to flow restoration in the culprit artery. No differences were noted in the median DTB (GT25: 158min [122-213] vs. 149 [118-219]; p=0.5) or in in-hospital mortality (8% vs. 7.2%; p=0.617). By implementing the regional STEMI care network, a constant decrease in DTB was noted throughout its years of operation., Conclusions: For STEMI patients presenting to a non-PCI capable center, a network care system for PCI mitigates the distance factor on DTB time. This is turn translates into comparable outcomes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The role of cells of the innate immune system in the pathogenesis of squamous cell carcinoma has been the subject of intense research in recent years. In particular, neutrophils have been shown recently to have either a pro-tumor or anti-tumor phenotype in different cancers. Here, we review the role of neutrophils as tumor microenvironment and signaling modulators of OSCC and their possible role as biomarkers of OSCC prognosis. Current evidence supports a pro-tumor role for neutrophils in OSCC, but more research is needed to clarify the precise mechanisms involved., (© 2014 Society for Leukocyte Biology.)

Patients with severe aortic stenosis and no obstructed coronary arteries are reported to have reduced coronary flow. Doppler evaluation of proximal coronary flow is feasible using transesophageal echocardiography. The present study aimed to assess the change in coronary flow in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). The left main coronary artery was visualized using transesophageal echocardiography in 90 patients undergoing TAVI using the Edwards SAPIEN valve. The peak systolic and diastolic velocities of the coronary flow and the time-velocity integral were obtained before and after TAVI using pulse-wave Doppler. Mean aortic gradients decreased from 47.1 ± 15.7 mm Hg before TAVI to 3.6 ± 2.6 mm Hg after TAVI (p <0.001). The aortic valve area increased from 0.58 ± 0.17 to 1.99 ± 0.35 cm(2) (p <0.001). The cardiac output increased from 3.4 ± 1.1 to 3.8 ± 1.0 L/min (p <0.001). Left ventricular end-diastolic pressure (LVEDP) decreased from 19.8 ± 5.4 to 17.3 ± 4.1 mm Hg (p <0.001). The following coronary flow parameters increased significantly after TAVI: peak systolic velocity 24.2 ± 9.3 to 30.5 ± 14.9 cm/s (p <0.001), peak diastolic velocity 49.8 ± 16.9 to 53.7 ± 22.3 cm/s (p = 0.04), total velocity-time integral 26.7 ± 10.5 to 29.7 ± 14.1 cm (p = 0.002), and systolic velocity-time integral 6.1 ± 3.7 to 7.7 ± 5.0 cm (p = 0.001). Diastolic time-velocity integral increased from 20.6 ± 8.7 to 22.0 ± 10.1 cm (p = 0.04). Total velocity-time integral increased >10% in 43 patients (47.2%). Pearson's correlation coefficient revealed the change in LVEDP as the best correlate of change in coronary flow (R = -0.41, p = 0.003). In conclusion, TAVI resulted in a significant increase in coronary flow. The change in coronary flow was associated mostly with a decrease in LVEDP., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: High on-treatment platelet reactivity (HTPR) has been shown to be associated with adverse cardiac events in patients undergoing percutaneous coronary intervention, but the effect of baseline hematologic parameters upon platelet reactivity remains controversial., Objective: The present study aims to evaluate the impact of hematocrit on 2 different assay methods used to assess on-treatment platelet reactivity to clopidogrel., Methods: We tested clopidogrel on-treatment platelet reactivity in 466 consecutive patients using VerifyNow P2Y12 (VN) and light transmission aggregometry (LTA) with adenosine diphosphate (ADP) 5 and 20 μM assays 6 to 24 hours after percutaneous coronary intervention. Patients were categorized into 4 groups according to baseline hematocrit. One-year major adverse cardiac events, including death, nonfatal myocardial infarction, and definite stent thrombosis, were collected., Results: Lower hematocrit was associated with higher P2Y12 reaction unit (PRU) and a higher rate of HTPR (P < .001) as measured by VN assay. No differences were seen among the 4 groups in platelet reactivity measured by LTA using ADP 5 μM (P = .23) and ADP 20 μM (P = .21). In a multivariable logistic regression model, baseline hematocrit was independently associated with PRU ≥208 (odds ratio [OR] 0.92, 95% CI 0.86-0.97, P = .005) but had no correlation with LTA ADP 5 μM ≥46% (OR 1.0, 95% CI 0.95-1.06, P = .88) or LTA ADP 20 μM ≥59% (OR 1.03, 95% CI 0.97-1.09, P = .39). In a logistic regression model, the addition of VN assay results, hematocrit, and interaction between the hematocrit and assay results had shown a significant influence on the area under curve for prediction of 1-year major adverse cardiac events compared with baseline clinical variables only for PRU (0.63 vs 0.76, P = .006) but not with LTA (0.64 vs 0.74, P = .13)., Conclusion: Baseline hematocrit has a differential influence on results of the ex vivo platelet functional assays. Lower baseline hematocrit was independently associated with HTPR by VN but not LTA. This may affect the interpretation of platelet function testing in patients with significant anemia., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: To assess the safety and efficacy everolimus-eluting stents (EES) compared with first-generation drug-eluting stents (DES) in patients with acute myocardial infarction (MI) undergoing primary percutaneous coronary intervention (PCI)., Background: EES have been associated with improved clinical outcomes compared to paclitaxel-eluting stents (PES) and with similar outcomes compared to sirolimus-eluting stents (SES)., Methods: A total of 520 patients who presented with ST-elevation myocardial infarction (STEMI) from 2003 to 2013, who underwent primary PCI with DES, were retrospectively analyzed. Of these, 247 received SES, 136 PES, and 137 EES. Patients were followed up to 2 years for major adverse cardiac events (MACE). Univariate and multivariate models detected correlates to outcome., Results: EES implantation, compared with PES and SES, resulted in comparable rates of MACE (8.8% vs. 16.2%, p=0.06 and 8.8% vs. 12.6%, respectively, p=0.26), stent thrombosis, MI, and target lesion revascularization. Patients who received EES had lower rates of all-cause mortality (3.7% vs. 12.6% vs. 9.4%, p=0.03) at 1-year follow up. However, in the univariate and multivariate analyses, stent type was not independently associated with the primary outcome or with all-cause mortality. Diabetes mellitus and number of stents implanted were independently associated with the primary outcome., Conclusion: While EES seem to be associated with better outcome when compared to PES, the main correlates of STEMI patients are the presence of diabetes and number of stents implanted, and not the type of stent used for intervention., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Longitudinal stent deformation (LSD) in drug-eluting stents (DES) has been described as a disruption of stent structure. This study aimed to compare first- versus second-generation DES with respect to their actual stent length post deployment., Methods: A total of 617 DES for de novo coronary lesions in 552 patients were analyzed. Intravascular ultrasound (IVUS) was utilized to compare the degree and rate of LSD among six different DES types. IVUS-measured stent length was compared to the labeled length for calculation of absolute difference in stent length and relative absolute difference (absolute difference divided by the labeled length)., Results: The baseline characteristics were comparable between groups, except for higher calcification in the sirolimus-eluting stent (SES) group (p=0.037). The absolute and relative difference in length showed the lowest degree in the SES group and the highest degree in the Endeavor zotarolimus-eluting stent group (p=0.085 and 0.078, respectively). The percentage of more than 5% relative absolute difference was the lowest in the SES group compared to the other groups (p=0.018). However, the percentage of significant (>15%) relative absolute difference was similar among groups (p=0.99). In multivariate linear regression analysis, labeled stent length and stent diameter, but not stent type, were identified as independent correlates to the absolute and relative difference in the actual stent length post-deployment., Conclusion: This IVUS analysis confirms that among second-generation DES, there is overall similar frequency and severity of LSD when deploying in common coronary lesions., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: An important subset of patients presenting with acute coronary syndrome (ACS) are found to have either normal coronaries (NCs) or non-obstructive coronary artery disease (NOCAD; lumen diameter narrowing <50%)., Objectives: To explore the characteristics and management strategies in this population in a real-world setting., Methods: The Acute Coronary Syndrome Israeli Survey (ACSIS) database was utilized to compare the characteristics and therapeutic approach for patients who underwent angiography for ACS and had either NC (n = 84; 2%), NOCAD (n = 79; 2%), or obstructive coronary artery disease (OCAD; n = 3523; 96%)., Results: Baseline characteristics were comparable, save for a younger age and a higher proportion of females in the NC group (P<.001 for both). Prior to admission, chronic anticoagulant therapy was more frequently used in the NC vs. the OCAD group (4.8% vs. 1.6%, respectively; P=.02). Recommended ACS evidence-based medications, both in-hospital and at discharge, were less frequently prescribed to patients with NC or NOCAD., Conclusions: In a real-world practice of ACS, underutilization of evidence-based medications in patients with NC or NOCAD was observed. Nonetheless, its prognostic significance is still unknown and must be explored in larger patient cohorts.

Background: Patients presenting with ST-segment elevation myocardial infarction (STEMI) represent a high-risk group for in-hospital adverse events and bleeding. The safety and outcomes of eptifibatide in addition to bivalirudin in this population have not been determined., Methods: Over an 11-year period, we identified 1849 STEMI patients undergoing primary percutaneous coronary intervention (PCI), of which 1639 received bivalirudin monotherapy compared with 210 patients who received both bivalirudin and provisional eptifibatide. Safety of combination therapy was assessed by the occurrence of thrombolysis in myocardial infarction (TIMI) major bleeding. In-hospital event rates of death, Q-wave myocardial infarction (MI), and acute stent thrombosis were evaluated for efficacy. Multivariate analysis was used to adjust for significant differences between groups., Results: Patients treated with bivalirudin plus eptifibatide, when compared with patients with bivalirudin monotherapy, had increased rates of cardiogenic shock (15.7% vs. 9.4%), aspiration thrombectomy (48.5% vs. 23.7%), pre-TIMI flow ≤1 (63.5% vs. 40%), and higher peak troponin I (93.65±92.7 vs. 49.16±81.59; all p <0.01). These, however, were not associated with differences in the primary end point after adjusting for significant baseline and procedural characteristics (OR: 1.63; 95% CI, 0.90-2.96, p=0.12). Importantly, TIMI major bleeding was not significantly different between groups (OR 1.78; 95% CI, 0.79-2.95, p=0.20)., Conclusion: The addition of eptifibatide to bivalirudin during primary PCI reflects a high-risk STEMI population. This therapy results in similar in-hospital outcomes without an increase in major bleeding. Therefore, when required, combination therapy may be considered in this population., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: This study utilized grayscale intravascular ultrasound (IVUS) to explore the relationship between high-density lipoprotein cholesterol (HDL-C) levels and culprit lesion characteristics in patients with coronary artery disease., Background: Low HDL-C is associated with an increased risk of cardiovascular events. Previous IVUS studies have suggested a significant association between lesion characteristics and cardiovascular events., Methods: According to HDL-C levels, 120 patients who underwent IVUS for native, de novo coronary lesions before any intervention were divided into a low HDL-C group (<40 mg/dL, n = 60) and a high HDL-C group (≥40 mg/dL, n = 60). Quantitative and qualitative IVUS analyses were performed to compare lesion characteristics., Results: Quantitative IVUS measurements showed no significant differences between the 2 groups. HDL-C level was not significantly correlated with remodeling index (r = 0.03, P = 0.78). However, attenuated plaque was more frequent in the low HDL-C group (48.3% vs. 28.3%, P = 0.02) and a greater percentage of attenuated plaque was found in this group (32.5 ± 21.3% vs. 21.0 ± 11.0%, P = 0.02). Moreover, when categorized into 4 groups according to HDL-C levels, the proportion of attenuated plaque (64.7% in group with <30 mg/dL, 41.9% in group with 30-39 mg/dL, 36.4% in group with 40-59 mg/dL, and 6.3% in group with ≥60 mg/dL; P = 0.001 for trend) was significantly different among groups. On multivariate analysis, only HDL-C and male gender were independently associated with the presence of attenuated plaque at the culprit lesions., Conclusions: Patients with low levels of HDL-C may be at increased risk of having a higher incidence of attenuated plaques., (© 2014, Wiley Periodicals, Inc.)

Transcatheter aortic valve implantation (TAVI) is associated with improved left ventricular (LV) function in patients with aortic stenosis (AS) and LV dysfunction; however, the outcome after TAVI of patients with low left ventricular ejection fraction (LVEF) is unclear. This study aimed to characterize the baseline, procedural, and long-term outcomes of patients with low LVEF undergoing TAVI and to assess the prognostic utility of pre-TAVI balloon aortic valvuloplasty (BAV) and dobutamine stress echocardiography (DSE) to predict TAVI benefits. Consecutive patients with symptomatic severe AS who underwent TAVI from 2007 to 2013 were analyzed. Two groups were compared: normal or near normal LV function (LVEF >45%) and LVEF ≤45% at baseline. In total, 371 patients were analyzed; 272 (73%) had preserved LVEF and 99 (27%) had low LVEF. Patients with low LVEF had higher Society of Thoracic Surgeons score and EuroSCORE. Short- and long-term mortality was similar between groups (1-year rate: 22.2% vs 22.4%, p = 0.79). Of the patients with low LVEF, 24% demonstrated improvement (≥10%) in LVEF at 30 days; patients with improvement had lower mortality at 1 year than those without (8% vs 27%, p = 0.06). Contractile reserve in DSE did not predict LVEF recovery in patients with low LVEF but did predict lower mortality. LVEF recovery after BAV predicted greater LVEF improvement after TAVI. In conclusion, patients with severe AS and impaired LV function benefit from TAVI and have comparable procedural outcomes compared with patients with preserved LVEF. Both DSE and BAV provide complementary data with regard to recovery of LVEF and mortality, both periprocedural and late after TAVI., (Copyright © 2014 Elsevier Inc. All rights reserved.)