Closing the gap: cardiovascular disease in women.

Cardiovascular disease (CVD) in women remains understudied, under-recognized, underdiagnosed and undertreated. Initiatives such as the Lancet Women and Cardiovascular Disease Commission help to identify sex and gender-related gaps in research, care and outcomes and to guide next steps in addressing them. This article highlights important aspects of the Lancet Commission report and expands on the evidence and proposed strategies for reducing the global burden of CVD in women. Furthermore, the article explores the benefits of cross-specialty collaborations for the treatment and prevention of CVD in women and discusses the impact of gender-related disparities in academic cardiology.

Primary prevention of cardiovascular disease in women.

Ischemic heart disease is the primary cause of cardiovascular disease (CVD) mortality in both men and women. Strategies targeting traditional modifiable risk factors are essential - including hypertension, smoking, dyslipidemia and diabetes mellitus - particularly for atherosclerosis, but additionally for stroke, heart failure and some arrhythmias. However, challenges related to education, screening and equitable access to effective preventative therapies persist, and are particularly problematic for women around the globe and those from lower socioeconomic groups. The association of female-specific risk factors (e.g. premature menopause, gestational hypertension, small for gestational age births) with CVD provides a potential window for targeted prevention strategies. However, further evidence for specific effective screening and interventions is urgently required. In addition to population-level factors involved in increasing the risk of suffering a CVD event, efforts are leveraging the enormous potential of blood-based 'omics', improved imaging biomarkers and increasingly complex bioinformatic analytic approaches to strive toward more personalized early disease detection and personalized preventative therapies. These novel tactics may be particularly relevant for women in whom traditional risk factors perform poorly. Here we discuss established and emerging approaches for improving risk assessment, early disease detection and effective preventative strategies to reduce the mammoth burden of CVD in women.

Analysis of trimodal and bimodal therapy in a selective-surgery paradigm for locally advanced oesophageal squamous cell carcinoma.

BACKGROUND: Long-term survival outcomes of trimodal therapy (TMT; chemoradiation plus surgery) and bimodal therapy (BMT; chemoradiation) have seldom been analysed. In a selective-surgery paradigm, the benefit of TMT in patients with a complete clinical response is controversial. Factors associated with survival in patients with a clinical complete response to chemoradiation were evaluated. METHODS: Patients with stage II-III oesophageal squamous cell carcinoma treated with TMT or BMT from 2002 to 2017 were evaluated. The BMT group consisted of patients who were otherwise eligible for surgery but underwent chemoradiation alone followed by observation. This group included patients who later had salvage oesophagectomy. Survival was evaluated and compared between TMT and BMT groups. Elastic net regularization was performed to select co-variables for Cox multivariable survival analysis in patients with a clinical complete response. RESULTS: Of 143 patients, 60 (41.9 per cent) underwent TMT and 83 (58.0 per cent) BMT. Patients who underwent TMT had longer median overall survival than those who had BMT (77 versus 33 months; P = 0.019). For patients with a clinical complete response, TMT achieved longer median overall survival than BMT (123 versus 55 months; P = 0.04). BMT had a high locoregional recurrence rate (48 versus 6 per cent; P < 0.001); 26 of 29 patients with locoregional recurrence in the BMT groupunderwent salvage resection. Cox multivariable analysis demonstrated that upper-mid oesophageal tumour location (hazard ratio (HR) 2.04; P = 0.024) and tumour length (HR 1.18; P = 0.046) were associated with worse survival. Although TMT was not associated with survival, it was a predictor of reduced recurrence (HR 0.28; P = 0.028). The maximum standardized uptake value after chemoradiation also predicted recurrence (HR 1.33; P < 0.001). CONCLUSION: In patients who achieve a clinical complete response, TMT reduces locoregional recurrence but may not prolong survival. The differences in survival outcomes may be due to patient selection; therefore, a selective-surgery strategy in oesophageal squamous cell carcinoma is a reasonable approach.

Sex-based outcomes after PCI in highbleeding risk patients: Results from the onyx one clear trial

BACKGROUND: While dual antiplatelet therapy (DAPT) constitutes the cornerstone of post-PCI pharmacotherapy, duration of DAPT in high bleeding risk (HBR) patients has not been fully defined especially with regard to sex. The results from the Onyx ONE Clear trial demonstrated favorable safety and efficacy after PCI with 1-month dual antiplatelet therapy (DAPT) in HBR patients treated with Resolute Onyx drug-eluting stents (DES). We sought to evaluate impact of sex on clinical outcomes in this trial. METHODS: In this prespecified subgroup analysis from Onyx ONE Clear, patients were divided into 2 groups according to sex. Primary endpoint was cardiac death or myocardial infarction (MI) from 1 month to 1 year. RESULTS: A total of 487 female patients (32%) and 1019 males (68%) were free from major ischemic events 1-month after PCI and were transitioned to single antiplatelet therapy.Women were older (p<0.001), had more HBR criteria (p=0.02), and higher rates of moderate/severe calcific lesions (p=0.03) compared to men. Men had higher rates of previous MI (p=0.003), atrial fibrillation (p=0.001), and multivessel coronary artery disease (p<0.001). Clinical outcomes between 1 and 12 months are shown in (Figure) and were similar for males and females except for target vessel revascularization which was greater for males (p=0.04). CONCLUSIONS: In HBR patients treated with Resolute Onyx DES and an abbreviated DAPT course of one month, rates of the primary endpoint of cardiac death or MI between 1 and 12 months were low and did not show any sex-based differences. These data support the use of an abbreviated DAPT regimen in men and women with HBR after PCI with Resolute Onyx DES.

Inertial flow focusing: a case study in optimizing cellular trajectory through a microfluidic MEMS device for timing-critical applications.

Although microfluidic micro-electromechanical systems (MEMS) are well suited to investigate the effects of mechanical force on large populations of cells, their high-throughput capabilities cannot be fully leveraged without optimizing the experimental conditions of the fluid and particles flowing through them. Parameters such as flow velocity and particle size are known to affect the trajectories of particles in microfluidic systems and have been studied extensively, but the effects of temperature and buffer viscosity are not as well understood. In this paper, we explored the effects of these parameters on the timing of our own cell-impact device, the µHammer, by first tracking the velocity of polystyrene beads through the device and then visualizing the impact of these beads. Through these assays, we find that the timing of our device is sensitive to changes in the ratio of inertial forces to viscous forces that particles experience while traveling through the device. This sensitivity provides a set of parameters that can serve as a robust framework for optimizing device performance under various experimental conditions, without requiring extensive geometric redesigns. Using these tools, we were able to achieve an effective throughput over 360 beads/s with our device, demonstrating the potential of this framework to improve the consistency of microfluidic systems that rely on precise particle trajectories and timing.

Polymer-based or polymer-free stents in patients at high bleeding risk

BACKGROUND Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus­coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drugcoated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P=0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P=0.007 for noninferiority). CONCLUSIONS Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.). (AU)

Morbidity following salvage esophagectomy for squamous cell carcinoma: the MD Anderson experience.

The survival advantage associated with the addition of surgical therapy in esophageal squamous cell carcinoma (ESCC) patients who demonstrate a complete clinical response to chemoradiotherapy is unclear, and many institutions have adopted an organ-preserving strategy of selective surgery in this population. We sought to characterize our institutional experience of salvage esophagectomy (for failure of definitive bimodality therapy) and planned esophagectomy (as a component of trimodality therapy) by retrospectively analyzing patients with ESCC of the thoracic esophagus and GEJ who underwent esophagectomy following chemoradiotherapy between 2004 and 2016. Of 76 patients who met inclusion criteria, 46.1% (35) underwent salvage esophagectomy. Major postoperative complications (major cardiovascular and pulmonary events, anastomotic leak [grade ≥ 2], and 90-day mortality) were frequent and occurred in 52.6% of the cohort (planned resection: 36.6% [15/41]; salvage esophagectomy: 71.4% [25/35]). Observed rates of 30- and 90-day mortality for the entire cohort were 7.9% (planned: 7.3% [3/41]; salvage: 8.6% [3/35]) and 13.2% (planned: 9.8% [4/41]; salvage: 17.1% [6/35]), respectively. In summary, esophagectomy following chemoradiotherapy for ESCC at our institution has been associated with frequent postoperative morbidity and considerable rates of mortality in both planned and salvage settings. Although a selective approach to surgery may permit organ preservation in many patients with ESCC, these results highlight that salvage esophagectomy for failure of definitive-intent treatment of ESCC may also constitute a difficult clinical undertaking in some cases.

Sex-based differences in outcomes with bivalirudin or unfractionated heparin for transcatheter aortic valve replacement: Results from the BRAVO-3 randomized trial.

BACKGROUND: Women comprise almost 50% of patients undergoing transcatheter aortic valve replacement (TAVR) and previous studies have indicated higher rates of procedural complications and bleeding in women compared to men. It is unknown whether men and women demonstrate a differential response to bivalirudin versus unfractionated heparin (UFH) in TAVR. We sought to evaluate outcomes by sex and type of anticoagulant from the Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement (BRAVO-3) trial of transfemoral TAVR. METHODS: BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). The primary endpoint was 48 h major bleeding defined as Bleeding Academic Research Consortium (BARC) type ≥3b. Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or stroke. Net adverse cardiovascular events (NACE) were a composite of BARC ≥3b bleeding or 30-day MACE. We examined the outcomes in men and women. RESULTS: The total cohort included 49% women (n = 391, 195 received bivalirudin and 196 UFH) and 51% men (n = 411, 209 received bivalirudin and 202 UFH). Women were older than men with fewer comorbidities including coronary artery disease, atrial fibrillation, diabetes but similar EuroSCORE I. Women received smaller sheath and device sizes compared with men without differences in the use of vascular closure devices. At 48-hr post-TAVR there was no difference in bleeding or vascular complications in women compared to men. The use of bivalirudin did not result in significantly lower bleeding at 48 hr or 30-days compared to UFH. CONCLUSIONS: There was no difference in early outcomes with bivalirudin versus UFH in men or women undergoing contemporary TAVR. © 2016 Wiley Periodicals, Inc.

Current controversies in PCI pharmacotherapy.

Coronary artery disease and atherothrombosis are complex pathologic entities. The intricate interplay between anatomical, cellular and molecular factors characterizes their pathogenesis and determines their clinical manifestations. Coronary artery revascularization strategies, by restoring myocardial blood perfusion, only partially treat ischemic heart disease in its complexity. Pharmacological therapies targeting molecular and cellular components involved in the pathophysiology of atherothrombosis are mandatory in order to prevent cardiovascular complications during and after revascularization and therefore improve clinical outcomes. The developments of antithrombotic pharmacotherapies occurred as a result of an improved understanding of the mechanisms underlying atherothrombotic disease. Unfortunately, the optimal antithrombotic therapy, in both acute and chronic settings, often set significant challenges in daily practice. The main objective of optimal antithrombotic therapies, targeting coagulation factors or the platelet system, is to maximize the anti-thrombotic efficacy while minimizing the bleeding risk. The subtle balance between ischemic and bleeding risk is a complex clinical conundrum that involves pharmacologic factors, the clinical phenotype of coronary artery disease and patient's clinical comorbidities. In a contemporary era, in which a broad armamentarium of pharmacologic agents and diagnostic tools are available, physician practice should shift toward a progressively more customized patient care. For this purpose, selection of the optimal acute and chronic percutaneous coronary intervention (PCI) pharmacotherapy, in terms of potency, duration and adherence, cannot disregard an individualized and careful evaluation of the patient's ischemic and hemorrhagic risk. It is within this context that in the present review article we sought to expose the current topics of debate and controversies in acute and chronic anticoagulant and antiplatelet therapies in patients undergoing PCI.

Rapid identification by surface-enhanced Raman spectroscopy of cancer cells at low concentrations flowing in a microfluidic channel.

Reliable identification and collection of cells from bodily fluids is of growing interest for monitoring patient response to therapy and for early detection of disease or its recurrence. We describe a detection platform that combines microfluidics with surface-enhanced Raman spectroscopy (SERS) for the identification of individual mammalian cells continuously flowing in a microfluidics channel. A mixture of cancerous and noncancerous prostate cells was incubated with SERS biotags (SBTs) developed and synthesized by us, then injected into a flow-focused microfluidic channel, which forces the cells into a single file. The spectrally rich SBTs are based on a silver nanoparticle dimer core labeled with a Raman-active small reporter molecule paired with an affinity biomolecule, providing a unique barcode whose presence in a composite SERS spectrum can be deconvoluted. Individual cancer cells passing through the focused laser beam were correctly identified among a proportionally larger number of other cells by their Raman signatures. We examine two deconvolution strategies: principal component analysis and classical least-squares. The deconvolution strategies are used to unmix the overall spectrum to determine the relative contributions between two SBT barcodes, where one SBT barcode indicates neuropilin-1 overexpression, while a second SBT barcode is more universal and indicates unspecific binding to a cell's membrane. Highly reliable results were obtained for all of the cell mixture ratios tested, the lowest being 1 in 100 cells.

Role of new sirolimus self-apposing stent in coronary interventions.

Device technology in interventional cardiology is continuously evolving. Self-expandable (SE) coronary artery stents were the first device to be implanted within a human coronary artery. However, because of their initial limitations, balloon-expandable (BE) stents were predominantly developed and used in the last 30 years. Unfortunately, in challenging anatomical settings such as bifurcation lesions, large, ectatic or aneurysmal vessels, tapered vessels or vasoconstricted arteries, outcomes with BE stents are not always optimal. The Stentys (Stentys SA, Paris, France) SE nitinol stents were initially developed for the treatment of coronary bifurcation lesions. The understanding of the underlying mechanism involved in incomplete stent apposition and subsequent stent thrombosis led to the introduction of self-apposing stents in the treatment of acute coronary syndrome in order to overcome the limitations of drug-eluting stents in presence of high thrombus burden. In this regard, Stentys allows a progressive stent expansion which could reduce the rates of incomplete stent apposition by conforming to vascular remodeling. Enhancing the advantages of this technology by adding the release of an antiproliferative drug to prevent restenosis is even more attractive and potentially effective. Recently, the results of the new Stentys sirolimus-eluting stent have been reported. This article provides an overview of the pathobiological rational, device characteristics and results of the new Stentys self-expandable sirolimus-eluting stent.

Endothelial progenitor cell mobilization by preoperative exercise: a bone marrow response associated with postoperative outcome.

BACKGROUND: Preoperative anaemia is associated with increased morbidity in patients undergoing major surgery. Whether erythrocytes are the only bone-marrow-derived cell lineage that associates with increased surgical complications is unknown. This prospective observational trial studied the mobilization of endothelial progenitor cells (EPCs) in response to exercise in association with postoperative complications. METHODS: After IRB approval, 60 subjects undergoing major thoracic surgery were exercised to exhaustion (peak V̇(O2)). Peripheral blood collected before and after peak exercise was quantified for EPC lineages by fluorescence-activated cell sorter analysis. Complication analysis was based on the Clavien-Dindo classification. RESULTS: Exhaustive exercise increased EPC [CD45-133+34+ cells=150 (0.00-5230) to 220 (0.00-1270) cells µl(-1); median change (range)=20 (-4,180-860) cells µl(-1); P=0.03] but not mature endothelial cell (EC) subpopulations. Pre-exercise levels [odds ratio (OR)=0.86, 95% confidence interval (CI): 0.37-2.00, P=0.72), change after exercise as a continuous variable (OR=0.95, 95% CI: 0.41-2.22, P=0.91) and a positive response after exercise (change >0 cells µl(-1); OR=0.41, 95% CI: 0.13-1.28, P=0.12) were not statistically significantly associated with the incidence of postoperative complications. Post-hoc receiver operating characteristic curve analyses revealed that subjects with a CD45-133+34+ increase ≥60 cells µl(-1) in response to exercise suffered fewer postoperative complications [86% sensitivity, 48% specificity and AUC=0.67 (95% CI: 0.52-0.81)]. CONCLUSIONS: Preoperative exercise induces EPC into the peripheral circulation. Subjects with a poor EPC response had a pre-existing propensity for postoperative complications. This warrants further research into the role of bone marrow function as a critical component to endothelial repair mechanisms. CLINICAL TRIAL REGISTRATION: IRB 2003-0434 (University of Texas M.D. Anderson Cancer Center, Houston, TX, USA).

Current developments in dual antiplatelet therapy after stenting.

Dual antiplatelet therapy (DAPT) with acetylsalicylic acid and an inhibitor of the adenosine diphosphate platelet receptor P2Y12 has been shown to reduce the risk of stent thrombosis (ST), myocardial infarction and cardiac death after percutaneous coronary intervention (PCI) with bare-metal stents (BMS) and drug-eluting stents (DES). However, while there is consensus on 1-month DAPT after BMS, the optimal duration and the risk-benefit ratio of DAPT duration after DES implantation remains controversial. Controversy surrounding this issue is demonstrated by differences in guideline recommendations for DAPT duration after PCI with DES. For example, while the ACC/AHA recommends a minimum of 12 months, ESC guidelines recommend at least 6 months of DAPT. Recent reports suggest that 6 months of DAPT after second-generation DES implantation might be safe compared with longer durations. Large randomized controlled trials powered to examine ST and bleeding events are currently ongoing and will shed novel insight on unresolved concerns and inform medical practice in the foreseeable future. In the present review, we critically and comprehensively examine the current level of evidence regarding the optimal duration of DAPT after PCI with DES and illustrate new and future perspectives surrounding this rapidly changing field.

Expression profiling stratifies mesothelioma tumors and signifies deregulation of spindle checkpoint pathway and microtubule network with therapeutic implications.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a lethal neoplasm exhibiting resistance to most treatment regimens and requires effective therapeutic options. Though an effective strategy in many cancer, targeted therapy is relatively unexplored in MPM because the therapeutically important oncogenic pathways and networks in MPM are largely unknown. MATERIALS AND METHODS: We carried out gene expression microarray profiling of 53 surgically resected MPMs tumors along with paired normal tissue. We also carried out whole transcriptomic sequence (RNA-seq) analysis on eight tumor specimens. Taqman-based quantitative Reverse-transcription polymerase chain reaction (qRT-PCR), western analysis and immunohistochemistry (IHC) analysis of mitotic arrest deficient-like 1 (MAD2L1) was carried out on tissue specimens. Cell viability assays of MPM cell lines were carried out to assess sensitivity to specific small molecule inhibitors. RESULTS: Bioinformatics analysis of the microarray data followed by pathway analysis revealed that the mitotic spindle assembly checkpoint (MSAC) pathway was most significantly altered in MPM tumors with upregulation of 18 component genes, including MAD2L1 gene. We validated the microarray data for MAD2L1 expression using quantitative qRT-PCR and western blot analysis on tissue lysates. Additionally, we analyzed expression of the MAD2L1 protein by IHC using an independent tissue microarray set of 80 MPM tissue samples. Robust clustering of gene expression data revealed three novel subgroups of tumors, with unique expression profiles, and showed differential expression of MSAC pathway genes. Network analysis of the microarray data showed the cytoskeleton/spindle microtubules network was the second-most significantly affected network. We also demonstrate that a nontaxane small molecule inhibitor, epothilone B, targeting the microtubules have great efficacy in decreasing viability of 14 MPM cell lines. CONCLUSIONS: Overall, our findings show that MPM tumors have significant deregulation of the MSAC pathway and the microtubule network, it can be classified into three novel molecular subgroups of potential therapeutic importance and epothilone B is a promising therapeutic agent for MPM.

Concordance of studies for nodal staging is prognostic for worse survival in esophageal cancer.

Pretreatment clinical staging in esophageal cancer influences prognosis and treatment strategy. Current staging strategies utilize multiple imaging modalities, and often the results are contradictory. No studies have examined the implications of concordance of computed tomography (CT), positron emission tomography (PET), and endoscopic ultrasound (EUS) when used for the evaluation of nodal disease. The objective of this study was to determine if concordance of CT, PET, or EUS for nodal disease predicts worse overall survival. We reviewed 615 esophageal cancer patients with pretreatment CT, PET, and EUS that underwent esophagectomy for survival outcomes based on concordance of studies for nodal disease. Concordant N+ is defined as two or three studies positive for nodal disease; non-concordant N+ is defined as only one positive study. Node-positive disease by any study predicted shorter survival than node-negative disease (42% vs. 73% 5-year survival; P<0.001). Additionally, non-concordant N+ patients had shorter survival than N- patients (52% vs. 73% 5-year survival; P<0.001). Concordant N+ patients had shorter survival than non-concordant N+ patients (38- vs. 61-month median survival; P=0.017). There were no statistically significant differences in survival based on specific combinations of studies. When PET was disregarded, patients with both CT+ and EUS+ had shorter survival than patients with either CT+ or EUS+ (39- vs. 58-month median survival; P=0.029). Pretreatment CT, PET, or EUS concordance for node-positive disease predicts shorter overall survival in patients that undergo esophagectomy for esophageal cancer. Predicting survival in esophageal cancer should consider the synergistic capabilities of CT, PET, and EUS in evaluating nodal status.

Aggregation kinetics of SERS-active nanoparticles in thermally stirred sessile droplets.

The aggregation kinetics of silver nanoparticles in sessile droplets were investigated both experimentally and through numerical simulations as a function of temperature gradient and evaporation rate, in order to determine the hydrodynamic and aggregation parameters that lead to optimal surface-enhanced Raman spectroscopic (SERS) detection. Thermal gradients promote effective stirring within the droplet. The aggregation reaction ceases when the solvent evaporates forming a circular stain consisting of a high concentration of silver nanoparticle aggregates, which can be interrogated by SERS leading to analyte detection and identification. We introduce the aggregation parameter, Γa ≡ τ(evap)/τ(a), which is the ratio of the evaporation to the aggregation time scales. For a well-stirred droplet, the optimal condition for SERS detection was found to be Γ(a,opt) = kc(NP)τ(evap) ≈ 0.3, which is a product of the dimerization rate constant (k), the concentration of nanoparticles (cNP), and the droplet evaporation time (τ(evap)). Near maximal signal (over 50% of maximum value) is observed over a wide range of aggregation parameters 0.05 < Γa < 1.25, which also defines the time window during which trace analytes can be easily measured. The results of the simulation were in very good agreement with experimentally acquired SERS spectra using gas-phase 1,4-benzenedithiol as a model analyte.

Rapid detection of drugs of abuse in saliva using surface enhanced Raman spectroscopy and microfluidics.

We present a microfluidic device that detects trace concentrations of drugs of abuse in saliva within minutes using surface-enhanced Raman spectroscopy (SERS). Its operation is demonstrated using methamphetamine. The detection scheme exploits concentration gradients of chemicals, fostered by the laminar flow in the device, to control the interactions between the analyte, silver nanoparticles (Ag-NPs), and a salt. Also, since all species interact while advecting downstream, the relevant reaction coordinates occur with respect to the position in the channel. The system was designed to allow the analyte first to diffuse into the side stream containing the Ag-NPs, on which it is allowed to adsorb, before salt ions are introduced, causing the Ag-NPs to aggregate, and so creating species with strong SERS signal. The device allows partial separation via diffusion of the analyte from the complex mixture. Also, the reproducible salt-induced NP aggregation decouples the aggregation reaction (necessary for strong SERS) from the analyte concentration or charge. This method enables the creation of a region where detection of the analyte of interest via SERS is optimal, and dramatically extends the classes of molecules and quality of signals that can be measured using SERS, compared to bulk solution methods. The spatial distribution of the SERS signals was used to map the degree of nanoparticle aggregation and species diffusion in the channel, which, together with numerical simulations, was used to describe the kinetics of the colloid aggregation reaction, and to determine the optimal location in the channel for SERS interrogation.

Drug-eluting balloons for side branch stenting during bifurcation percutaneous coronary intervention.

Drug-eluting balloons (DEB) were developed to address in-stent restenosis among other indications but have also recently been shown safe and efficacious in the context of bifurcation. By eliminating both the stent and the polymer, stent thrombosis can be avoided, while still delivering an antiproliferative agent to reduce the risk of restenosis. Bifurcation lesions account for approximately 15% to 20% of all percutaneous coronary interventions and reflect a higher risk of in-stent restenosis. Complex 2-stent techniques have been shown to increase the periprocedural myocardial infarction and stent thrombosis, while side branch restenosis rates remain a drawback for even provisional stenting. In-stent restenosis of complex bifurcation lesions can increase the complexity of the intervention strategy at a rate of about 14%, often caused by DES restenosis. Drug-eluting balloons have been shown to be a good interventional option in several randomized clinical trials to prevent and treat coronary in-stent restenosis as well as in nonrandomized series in the treatment of de novo lesions in small coronary vessels and bifurcation lesions. The next generation of DEB are being designed with improved coating platforms to provide more precise drug delivery to the tissue, which will enhance their efficacy.

Clinical parameters model for predicting pathologic complete response following preoperative chemoradiation in patients with esophageal cancer.

BACKGROUND: Approximately 25% of patients with esophageal cancer (EC) who undergo preoperative chemoradiation, achieve a pathologic complete response (pathCR). We hypothesized that a model based on clinical parameters could predict pathCR with a high (≥60%) probability. PATIENTS AND METHODS: We analyzed 322 patients with EC who underwent preoperative chemoradiation. All the patients had baseline and postchemoradiation positron emission tomography (PET) and pre- and postchemoradiation endoscopic biopsy. Logistic regression models were used for analysis, and cross-validation via the bootstrap method was carried out to test the model. RESULTS: The 70 (21.7%) patients who achieved a pathCR lived longer (median overall survival [OS], 79.76 months) than the 252 patients who did not achieve a pathCR (median OS, 39.73 months; OS, P = 0.004; disease-free survival, P = 0.003). In a logistic regression analysis, the following parameters contributed to the prediction model: postchemoradiation PET, postchemoradiation biopsy, sex, histologic tumor grade, and baseline (EUS)T stage. The area under the receiver-operating characteristic curve was 0.72 (95% confidence interval [CI] 0.662-0.787); after the bootstrap validation with 200 repetitions, the bias-corrected AU-ROC was 0.70 (95% CI 0.643-0.728). CONCLUSION: Our data suggest that the logistic regression model can predict pathCR with a high probability. This clinical model could complement others (biomarkers) to predict pathCR.

Patients with high body mass index tend to have lower stage of esophageal carcinoma at diagnosis.

High body mass index (H-BMI; ≥25 kg/m(2) ) is common in US adults. In a small cohort of esophageal cancer (EC) patients treated with surgery, H-BMI and diagnosis of early stage EC appeared associated. We evaluated a much larger cohort of EC patients. From a prospectively maintained database, we analyzed 925 EC patients who had surgery with or without adjunctive therapy. Various statistical methods were used. Among 925 patients, 69% had H-BMI, and 31% had normal body mass index (<25 kg/m(2) ; N-BMI). H-BMI was associated with men (P<0.001), Caucasians (P=0.064; trend), lower esophageal localization (P<0.001), adenocarcinoma histology (P<0.001), low baseline cT-stage (P=0.003), low baseline overall clinical stage (P=0.003), coronary artery disease (P=0.036), and diabetes (P<0.001). N-BMI was associated with weight loss (P<0.001), alcohol abuse (P=0.056; trend), ever/current smoking (P=0.014), and baseline cN+ (P=0.018). H-BMI patients with cT1 tumors (n=110) had significantly higher rates of gastresophageal reflux disease symptoms (P<0.001), gastresophageal reflux disease history (P<0.001), and Barrett's esophagus history (P<0.001) compared with H-BMI patients with cT2 tumors (n=114). Median survival of N-BMI patients was 36.66 months compared with 53.20 months for H-BMI patients (P=0.005). In multivariate analysis, older age (P<0.001), squamous histology (P=0.002), smoking (P=0.040), weight loss (P=0.002), high baseline stage (P<0.001), high number of ypN+ (P=0.005), high surgical stage (P<0.001), and American Society of Anesthesia scores, three out of four (P<0.001) were independent prognosticators for poor overall survival. We were able to perform propensity-based analysis of surgical complications between H-BMI and N-BMI patients. A comparison of fully matched 376 patients (188 with H-BMI and 188 with N-BMI) found no significant differences in the rate of complications between the two groups. This larger data set confirms that a fraction of H-BMI patients with antecedent history is diagnosed with early baseline EC. Upon validation of our data in an independent cohort, refinements in surveillance of symptomatic H-BMI patients are warranted and could be implemented. Our data also suggest that H-BMI patients do not experience higher rate of surgical complications compared with N-BMI patients.