Search

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 (r = 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 (r = 0.18; P = 0.07) and with per cent PB (r = 0.41; P, 0.001). This relationship remained significant for obstructive (r = 0.72; P < 0.001) and non-obstructive lesions (r = 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. [ABSTRACT FROM AUTHOR]

Immune cell–mesenchymal stem cell crosstalk modulates the process of repair and regeneration. In this study, a novel heterogeneous cell containing a matrix-based 3-dimensional (3D) tissue construct was used to study the interactions between stem cells from apical papilla (SCAPs) and macrophage for a comprehensive understanding on the cellular signaling mechanisms guiding inflammation and repair. SCAPs and macrophages were seeded with collagen in 3D-printed molds to generate self-assembled tissue constructs, which were exposed to 3 conditions: no stimulation, lipopolysaccharide (LPS), and interleukin (IL)-4 from 0 to 14 days. Specimens from each group were evaluated for cellular interactions, inflammatory mediators (IL-1β, tumor necrosis factor [TNF]-α, macrophage-derived chemokine [MDC], macrophage inflammatory protein [MIP]-1β, monocyte chemoattractant protein [MCP]-1, IL-6, IL-8, transforming growth factor [TGF]-β1, IL-1RA, IL-10), expression of surface markers (CD80, 206), transcription factors (pSTAT1, pSTAT6), and SCAP differentiation markers (dentin sialophosphoprotein [DSPP], dentin matrix acidic phosphoprotein 1 [DMP-1], and alizarin red) using confocal laser scanning microscopy and multiplex cytokine profiling from 2 to 14 days. SCAP and macrophages displayed a cytokine-mediated interaction and differentiation characteristics. The increased pro-inflammatory cytokines/chemokines, IL-1β, TNF-α, MDC, and MIP-1β, in the earlier phase followed by the higher ratio of pSTAT6/pSTAT1 and decreased CD206 (P <.05), indicated a distinct polarization behavior in macrophages during repair in the LPS group. Conversely, the equal ratio of pSTAT6/pSTAT1, late increase in CD206, and amplified secretion of IL-1RA, IL-10, and TGF-β1 (P <.05) in the anti-inflammatory environment, directed alternative macrophage polarization, promoting SCAP differentiation and tissue modeling in IL-4 group. The novel 3D organoid system developed in this study allowed a comprehensive analysis of the SCAP-macrophage interactions during inflammation and healing, providing a deeper insight on the periapical dynamics of the immature tooth. [ABSTRACT FROM AUTHOR]

Re-operation after coronary artery bypass grafting (CABG) is associated with increased risk for morbidity and mortality. Transcatheter aortic valve implantation (TAVI) is an alternative for patients with aortic stenosis, but the outcomes of patients with a history of CABG are unknown. The aim of this study was to explore the association between previous CABG and the outcome of patients undergoing TAVI. Out of 372 consecutive patients who underwent TAVI from 2007 to 2013, 122 (32.8%) had previous CABG, whereas 250 (67.2%) did not. A comparison was made between groups. Subgroup analysis compared patients with and without previous CABG in 3 patient subsets: inoperable, operable, and those who underwent transapical TAVI. Patients with previous CABG were younger (81.99 ± 6.78 vs 84.81 ± 7.06 years, respectively, p <0.001). These patients also had more high-risk features (e.g., peripheral vascular disease, previous myocardial infarction, past cerebrovascular disease, and lower average left ventricular ejection fraction (p <0.05 for all). Procedural aspects were mostly similar between groups. No disparities in mortality rates at 1 year were noted (22.1% vs 21.6%, respectively, p[0.91). Subgroup analyses yielded similar outcomes for all 3 groups. In conclusion, although patients with previous CABG present with more high-risk features, they share similar short- and long-term outcomes with patients without previous CABG, irrespective of their surgical risk. This includes patients who underwent transapical access. TAVI in patients with previous CABG is safe and does not confer a significant risk for adverse outcome. [ABSTRACT FROM AUTHOR]

Aortic valve annular complex was rediscovered after the introduction of transcatheter aortic valve replacement; and imaging has been crucial in determining the annular geometry. Although the procedure has evolved, complications related to the annular mechanical response following valve implantation, such as aortic insufficiency, still occur in practice. We documented the feasibility of invasive assessment of aortic valve annular complex and the detection of induced aortic insufficiency via intravascular ultrasound with ChromaFlo® technology in a porcine model. [ABSTRACT FROM AUTHOR]

Autophagy plays an important role in immunity to microbial pathogens. The autophagy system can target bacteria in phagosomes. promoting phagosome maturation and preventing pathogen escape into the cytosol. Recently, Toll-like receptor (TLR) signaling from phagosomes was found to initiate their targeting by the autophagy system, but the mechanism by which TLR signaling activates autophagy is unclear. Here we show that autophagy targeting of phagosomes is not exclusive to those containing TLR ligands. Engagement of either TLRs or the Fcy receptors (FcγRs) during phagocytosis induced recruitment of the autophagy protein LC3 to phagosomes with similar kinetics. Both receptors are known to activate the NOX2 NADPH oxidase, which plays a central role in microbial killing by phagocytes through the generation of reactive oxygen species (ROS). We found that NOX2generated ROS are necessary for LC3 recruitment to phagosomes. Antibacterial autophagy in human epithelial cells, which do not express NOX2, was also dependent on ROS generation. These data reveal a coupling of oxidative and nonoxidative killing activities of the NOX2 NADPH oxidase in phagocytes through autophagy. Furthermore, our results suggest a general role for members of the NOX family in regulating autophagy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

It has come to the authors' attention that the representative image of the unstimulated UMSCC1 spheroid at Day 1 in Fig. 1a was selected from the wrong data set. [ABSTRACT FROM AUTHOR]

Invadopodia are actin-rich, proteolytic structures that enable cancer cell to invade into the surrounding tissues. Several in vitro invasion assays have been used in the literature ranging from directional quantitative assays to complex three-dimensional (3D) analyses. One of the main limitations of these assays is the lack of quantifiable degradation-dependent invasion in a three-dimensional (3D) environment that mimics the tumor microenvironment. In this article, we describe a new invasion and degradation assay based on the currently available tumor spheroid model that allows long-term high-resolution imaging of the tumor, precise quantification, and visualization of matrix degradation and multichannel immunocytochemistry. By incorporating a degradation marker (DQ-Green BSA) into a basement-membrane matrix, we demonstrate the ability to quantitate cancer cell-induced matrix degradation in 3D. Also, we describe a technique to generate histological sections of the tumor spheroid allowing the detection of invadopodia formation in the 3D tumor spheroid. This new technique provides a clear advantage for studying cancer in vitro and will help address critical questions regarding the dynamics of cancer cell invasion. [ABSTRACT FROM AUTHOR]

Oral cancer is a devastating disease and is commonly preceded by a range of oral premalignant disorders. We investigated the expression of PD-1 and PD-L1 in oral epithelial dysplasia (OED) that progressed to oral squamous cell carcinoma (OSCC) compared to non-progressing dysplasia. 49 oral biopsies were analyzed, including 19 progressing cases, 20 cases did not progress, and 10 OSCC. Samples were stained with monoclonal antibodies for PD-1 and PD-L1, followed by conventional peroxidase reaction immunohistochemistry (IHC) imaged under light microscopy or fluorescent immunohistochemistry (FIHC) imaged using a confocal microscope. Images were analyzed using a novel semi-automated analysis protocol. PD-1/PD-L1 expression was assessed at the epithelium/tumor cells (TC) and at inflammatory cells in lamina propria. Our results show a significant increase in PD-L1 expression in progressing compared to non-progressing dysplasia. Using FIHC, we showed increased PD-L1 expression, increased nuclear density in progressing dysplasia and a better interobserver agreement compared with IHC. We developed a new FIHC-based quantitative method to study PD-1/PD-L1 expression in FFPE samples and showed that PD-L1 is highly expressed in premalignant lesions progressing to cancer. Our results suggest that immunomodulation via PD-L1/PD-1 pathway occurs prior to malignant transformation. [ABSTRACT FROM AUTHOR]

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/m2 (Log-ranked p=0.0286 and p=0.0432, respectively). Four subgroups with pre- and post-valve implant CI changes (L/min/m2) were compared: [1] pre<1.9, stable_post<1.9; [2] pre<1.9, improved_post≥1.9; [3] pre≥1.9, stable_post≥1.9; and [4] pre≥1.9, worsened_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. [ABSTRACT FROM AUTHOR]

To review the molecular mechanisms and biological roles of granulocyte-macrophage colony-stimulating factor (GM-CSF) in head and neck squamous cell carcinoma, highlighting its potential clinical applications. The search terms "granulocyte-macrophage colony-stimulating factor", "GM-CSF", "CSF2″ and "head and neck squamous cell carcinoma" or "head and neck cancer" were queried in the PubMed/MEDLINE and Scopus databases. Despite of being a widely expressed cytokine, the number of studies investigating the specific roles of GM-CSF in head and neck cancer was limited. Most of them investigated GM-CSF in conjunction with other cytokines. When studied alone, conflicting findings were observed in head and neck squamous cell carcinoma. GM-CSF has been shown to induce angiogenesis and local tumor invasion. Additionally, it has also been implicated in immune evasion. On the other hand, GM-CSF stimulated the differentiation of dendritic cells, which are responsible for presenting tumor antigens, and for the regulation of T cell function. Even with these paradoxical effects, there are few studies investigating the potential of GM-CSF as adjuvant therapy in head and neck cancer. The effects of GM-CSF in head and neck cancer may be pro- or antitumor. Understanding how one arm and not the other is activated is essential to assess the applicability and the safety of this cytokine as a therapeutic agent. • Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) has dual roles in cancer. • High expression of GM-CSF is reported in more than half of head and neck cancer. • GM-CSF increases angiogenesis, invasion, and immune evasion in head and neck cancer. • GM-CSF also enhances inflammatory response in head and neck cancer. [ABSTRACT FROM AUTHOR]

Exosomes are extracellular vesicles found in saliva and other body fluids. These vesicles range in size from 30 to 150 nm and play a crucial role in intercellular communication, transporting different biomolecules, actively targeting cells. These vesicles regulate both physiological and pathological processes within recipient cells. MicroRNAs (miRs) are transported within exosomes and are delivered to target cells where they influence signaling pathways, taking on a crucial regulatory role in oncogenesis; for example, they are implicated in progression and infiltration of various cancers, such as head and neck squamous cell carcinoma (HNSCC). A systematic literature search based on specific keywords, according to the PRISMA guidelines, was carried out on PubMed, Web of Science, Scopus, and Google Scholar. Only original articles were selected during this review. The risk of bias was assessed by QUADAS-2. At the end of the selection process 9 articles were included. In these studies, 41 miRs showed differential expression between healthy subjects and patient with HNSCC. The techniques varied among studies for the extraction and analysis of exosomal miRs. We presented also salivary exosomal miRs pathways, to give insights about pathogenetic mechanisms. Exosomal microRNA are promising biomarkers for HNSCC detection. MiR-10b-5p, miR-486–5p, miR-24–3p, miR-412–3p, and miR-512–3p are the most promising markers applicable to diagnostics, while miR-1307–5p and miR-519c–3p resulted overexpressed and correlated to worse survival outcomes. • Salivary exosomal miRNAs are significant clinical promise in early diagnosis of HNSCC. • Salivary exosomal miRNAs are significant clinical promise in prognosis of HNSCC. • Salivary exosomal miRNAs as indicators of the tumor's stage. • Salivary exosomal miRNAs pathways in HNSCC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Gastric adenocarcinoma, commonly known as stomach cancer, has a predilection for metastasis to the peritoneum, which portends limited survival. The peritoneal metastatic cascade remains poorly understood, and existing models fail to recapitulate key elements of the interaction between cancer cells and the peritoneal layer. To explore the underlying cellular and molecular mechanisms of peritoneal metastasis, we developed an ex vivo human peritoneal explant model. Fresh peritoneal tissue samples were suspended, mesothelial layer down but without direct contact, above a monolayer of red-fluorescent dye stained AGS human gastric adenocarcinoma cells for 24 h, then washed thoroughly. Implantation of AGS cells within the explanted peritoneum and invasion beyond the mesothelial layer were examined serially using real-time confocal fluorescence microscopy. Histoarchitecture of the explanted peritoneum was preserved over 5 days ex vivo. Both implantation and invasion were suppressed by restoration of functional E-cadherin through stable transfection of AGS cells, demonstrating sensitivity of the model to molecular manipulation. Thus, our ex vivo human peritoneal explant model permits meaningful investigation of the pathways and mechanism that contribute to peritoneal metastasis. The model will facilitate screening of new therapies that target peritoneal dissemination of gastric, ovarian and colorectal cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]