Block Copolymer Micellization of DNA Origami Promotes Solubility in Organic Solvents.

The DNA origami technique allows the precise synthesis of complex, biocompatible nanomaterials containing small molecules, biomolecules, and inorganic nanoparticles. The negatively charged phosphates in the backbone make DNA highly water-soluble and require salts to shield its electrostatic repulsion. DNA origamis are therefore not soluble in most organic solvents. While this is not problematic for applications in biochemistry, biophysics, or nanomedicine, other potential applications, processes, and substrates are incompatible with saline solutions, which include the synthesis of many nanomaterials, and reactions in templated synthesis, the operation of nanoelectronic devices, or semiconductor fabrication. To overcome this limitation, we coated DNA origami with amphiphilic poly(ethylene glycol) polylysine block copolymers and transferred them into various organic solvents including chloroform, dichloromethane, acetone, or 1-propanol. Our approach maintains the shape of the nanostructures and protects functional elements bound to the structure, such as fluorophores, gold nanoparticles, or proteins. The DNA origami polyplex micellization (DOPM) strategy hence enables solubilization or a phase transfer of complex structures into various organic solvents, which significantly expands the use of DNA origami for a range of potential applications and technical processes.

Staged versus index procedure complete revascularization in ST-elevation myocardial infarction: A meta-analysis.

BACKGROUND: Complete revascularization of patients with ST-elevation myocardial infarction and multivessel coronary artery disease reduces adverse events compared to infarct-related artery only revascularization. Whether complete revascularization should be done as multivessel intervention during index procedure or as a staged procedure remains controversial. METHOD: We performed a meta-analysis of randomized controlled trials comparing outcomes of multivessel intervention in patients with ST-elevation myocardial infarction and multivessel coronary artery disease as staged procedure versus at the time of index procedure. Composite of death or myocardial infarction was the primary outcome. Mantel-Haenszel risk ratios were calculated using random effect model. RESULTS: Six randomized studies with a total of 1126 patients met our selection criteria. At a mean follow-up of 13 months, composite of myocardial infarction or death (7.2% vs 11.7%, RR: 1.66, 95%CI: 1.09-2.52, P = 0.02), all cause mortality (RR: 2.55, 95%CI: 1.42-4.58, P < 0.01), cardiovascular mortality (RR: 2.8, 95%CI: 1.33-5.86, P = 0.01), and short-term (<30 days) mortality (RR: 3.54, 95%CI: 1.51-8.29, P < 0.01) occurred less often in staged versus index procedure multivessel revascularization. There was no difference in major adverse cardiac events (RR: 1.14, 95%CI: 0.88-1.49, P = 0.33), repeat myocardial infarction (RR: 1.14, 95%CI: 0.68-1.92, P = 0.61), and repeat revascularization (RR: 0.92, 95%CI: 0.66-1.28, P = 0.62). CONCLUSION: In patients with ST-elevation myocardial infarction and multivessel coronary artery disease, a strategy of complete revascularization as a staged procedure compared to index procedure revascularization results in reduced mortality without an increase in repeat myocardial infarction or need for repeat revascularization.

Design and Synthesis of Triangulated DNA Origami Trusses.

DNA nanotechnology offers unique control over matter on the nanoscale. Here, we extend the DNA origami method to cover a range of wireframe truss structures composed of equilateral triangles, which use less material per volume than standard multiple-helix bundles. From a flat truss design, we folded tetrahedral, octahedral, or irregular dodecahedral trusses by exchanging few connector strands. Other than standard origami designs, the trusses can be folded in low-salt buffers that make them compatible with cell culture buffers. The structures also have defined cavities that may in the future be used to precisely position functional elements such as metallic nanoparticles or enzymes. Our graph routing program and a simple design pipeline will enable other laboratories to make use of this valuable and potent new construction principle for DNA-based nanoengineering.

Block Copolymer Micellization as a Protection Strategy for DNA Origami.

DNA nanotechnology enables the synthesis of nanometer-sized objects that can be site-specifically functionalized with a large variety of materials. For these reasons, DNA-based devices such as DNA origami are being considered for applications in molecular biology and nanomedicine. However, many DNA structures need a higher ionic strength than that of common cell culture buffers or bodily fluids to maintain their integrity and can be degraded quickly by nucleases. To overcome these deficiencies, we coated several different DNA origami structures with a cationic poly(ethylene glycol)-polylysine block copolymer, which electrostatically covered the DNA nanostructures to form DNA origami polyplex micelles (DOPMs). This straightforward, cost-effective, and robust route to protect DNA-based structures could therefore enable applications in biology and nanomedicine where unprotected DNA origami would be degraded.

Biomolecular inflammatory response to surgical energy usage in laparoscopic surgery: results of a randomized study.

OBJECTIVE: Use of surgical energy is integral to laparoscopic surgery (LS). Energized dissection (ED) has a potential to impact the biomolecular expression of inflammation due to ED-induced collateral inflammation. We did this triple-blind randomized controlled (RCT) study to assess this biomolecular footprint in an index LS, i.e., laparoscopic cholecystectomy (LC). METHODS AND PROCEDURES: This RCT was conducted in collaboration with tertiary-level institutions, from January 2014 to December 2014 with institutional review board clearance. Consecutive, unselected, consenting candidates for LC were randomized (after anesthesia induction) into group I (ED) and group II (non-ED). They were managed with compliance to universal protocols for ethics, informed consent, anesthesia, drug usage and clinical pathway with blinded observers. Biomolecular inflammatory markers, i.e., interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and highly sensitive CRP (HS-CRP), were measured with blood drawn juxta-preoperatively (H0), at 4 h (H4) and at 24 h (H24). The quantitative changes induced by ED on IL-6, TNF-α and HS-CRP at H0, H4 and H24 with their kinetic behavior were the study endpoint. Prospective data were analyzed statistically with a p value of <0.05 being significant. RESULTS: Two cases from the ED group had biliary injury and hence were withdrawn from analysis. The ED (n = 49) and non-ED (n = 51) groups had similar demographic, clinical and H0 biomolecular variables. There was a significant increase in IL-6, TNF-α and HS-CRP from H0 to H4 in both the groups (p values <0.001). From H4 to H24, all three cytokines showed significant increase in ED group (p < 0.05), whereas in the non-ED group, IL-6 showed significant fall (p = 0.004) and TNF-α showed no significant change (p = 0.063). Both the groups showed H4-H24 elevation of HS-CRP (p = 0.000). CONCLUSION: Energized dissection adds to the cytokine-mediated postoperative inflammation. The additional ED-induced inflammation can be measured objectively by IL-6 and TNF-α levels. CLINICAL TRIALS REGISTRY: Clinical Trials Registry, India (REF/2014/06/007153).

Biomechanical strain induces elastin and collagen production in human pluripotent stem cell-derived vascular smooth muscle cells.

Blood vessels are subjected to numerous biomechanical forces that work harmoniously but, when unbalanced because of vascular smooth muscle cell (vSMC) dysfunction, can trigger a wide range of ailments such as cerebrovascular, peripheral artery, and coronary artery diseases. Human pluripotent stem cells (hPSCs) serve as useful therapeutic tools that may help provide insight on the effect that such biomechanical stimuli have on vSMC function and differentiation. In this study, we aimed to examine the effect of biomechanical strain on vSMCs derived from hPSCs. The effects of two types of tensile strain on hPSC-vSMC derivatives at different stages of differentiation were examined. The derivatives included smooth muscle-like cells (SMLCs), mature SMLCs, and contractile vSMCs. All vSMC derivatives aligned perpendicularly to the direction of cyclic uniaxial strain. Serum deprivation and short-term uniaxial strain had a synergistic effect in enhancing collagen type I, fibronectin, and elastin gene expression. Furthermore, long-term uniaxial strain deterred collagen type III gene expression, whereas long-term circumferential strain upregulated both collagen type III and elastin gene expression. Finally, long-term uniaxial strain downregulated extracellular matrix (ECM) expression in more mature vSMC derivatives while upregulating elastin in less mature vSMC derivatives. Overall, our findings suggest that in vitro application of both cyclic uniaxial and circumferential tensile strain on hPSC-vSMC derivatives induces cell alignment and affects ECM gene expression. Therefore, mechanical stimulation of hPSC-vSMC derivatives using tensile strain may be important in modulating the phenotype and thus the function of vSMCs in tissue-engineered vessels.

Outcomes of laparoscopic cholecystectomy done with surgical energy versus done without surgical energy: a prospective-randomized control study.

OBJECTIVE: Laparoscopic cholecystectomy (LC), a gold standard procedure can be done without energized dissection (ED). We did a randomized study for the outcomes of LC done with ED or without ED, i.e., with cold dissection (CD). METHODS AND PROCEDURES: At a tertiary level institution, open-ended prospective-randomized control study was conducted between September 2008 and June 2013. Consecutive, unselected, consenting candidates for LC were enrolled following standard ethics, informed consent, anesthesia, and clinical pathway protocol. They were allocated to control group (LC with ED) or study group (LC with CD, as per our published technique with the option for rescue ED). The study points were based upon Clavien-Dindo grading of postoperative complications. They were either, peri-operative events potentially affecting, hospital stay (Grade I) or Grade II-V, e.g., peri-operative hemodynamic instability, needing intervention/blood transfusion, injury to biliary ducts/hollow viscous, postoperative biliary leak, postoperative re-intervention, re-hospitalization, mortality, and any adverse event during a 90-day follow-up period. The data were prospectively collected in an integrated "hospital information system" that could be retrieved only by independent external coordinators. RESULTS: Demographics, co-morbidities, and gallbladder inflammation profile of the control group (n = 361) and study group (n = 384) were comparable. There was no rescue ED usage in the study group. Hospital stay (Grade I adverse outcome dependent) was longer, i.e., 1.6 ± 1.03 in the control versus 1.35 ± 1.2 days in the study group (p < 0.001). Grade II-IV complications were significantly more (p < 0.009) in control group. There was one common bile duct (CBD) injury in each group. The index bilio-enteric anastomosis for CBD injury in control group failed and needed a revision with multiple interventions. There was one grade V adverse outcome, i.e., mortality in the control group. CONCLUSION: Avoiding the use of ED in LC is associated with better outcomes.

Biodosimetric analysis of head and neck cancer patients undergoing radiotherapy by dicentric chromosome aberration assay.

BACKGROUND: Biodosimetry is the quantification of absorbed radiation dose using biological material obtained from an exposed individual. Radiation can cause different types of chromosomal aberrations, including stable aberrations like translocations and unstable ones like micronuclei, dicentric chromosomes (DC), acentric, and ring forms. Dicentric chromosome assay has become the "gold standard" for cytogenetic biodosimetry due to its reproducibility, specificity (low baseline rates), and sensitivity to low doses. Using existing calibration curves and models obtained from in vitro irradiation of blood, the yield of DCs can be used to estimate the average whole-body absorbed dose. PURPOSE: To evaluate and compare the in vivo dose-response relation of DC aberration formation in peripheral blood lymphocytes of head and neck cancer (HNC) patients undergoing radiotherapy (RT) alone, cisplatin-based chemoradiation (CCRT), accelerated fractionation RT (AFRT), and CCRT with gefitinib (GCRT). METHODOLOGY: This prospective observational and analytical study was conducted from 2018 to 2021 in the Department of Radiation Oncology and Genetic Lab of tertiary care, teaching hospital after approval from the Institutional Ethics Committee. Biodosimetric analysis was done weekly in patients undergoing RT (n = 20) versus CCRT (n = 20), CCRT (n = 12) versus AFRT (n = 12), and CCRT (n = 6) versus GCRT (n = 6). The yield of DCs was measured in blood samples taken before starting treatment, that is, day 0 and during RT on days 6, 11, and 16 in RT alone versus CCRT; on days 7 and 13 in CCRT versus AFRT; and days 6 and 11 in CCRT versus GCRT from a blood sample drawn 1-2 h after RT. Phytohemagglutinin-stimulated lymphocytes were cultured using heparinized blood in RPMI-1640 medium supplemented with fetal bovine serum. Cells were arrested at metaphase using demecolcine, harvested by centrifugation, mounted, and stained with Giemsa. Cytogenetic analysis was performed by analyzing at least 100 metaphases with well-spread chromosomes. DC aberrations and acentric fragments were identified and recorded. To standardize the findings as per the customized field for every patient, the mean DC yield per cm2 of the irradiated area was calculated and compared. RESULTS: The mean yield of DC/cm2 in the CCRT group was greater than the RT alone group by 16.33%, 28.57%, and 18.68% on days 6, 11, and 16 of treatment, respectively. This difference between the two groups at day 6 (P = 0.001), day 11 (P < 0.001), and day 16 (P < 0.001) was found to be statistically significant. The mean yield of DC/cm2 in the CCRT group was greater than the AFRT group by 7.9% and 18.3% on days 7 and 13 of treatment, respectively. This difference at day 7 (P < 0.001) and day 13 (P < 0.001) was found to be statistically significant. The mean yield of DC/cm2 in the CCRT group was greater than the GCRT group by 22.7% and 21.8% on days 6 and 11 of treatment, respectively. The difference at day 6 (P = 0.01) was statistically significant but, on day 11 (P = 0.065) this difference was found insignificant. CONCLUSION: There is a dose-dependent increase in the yield of DCs in lymphocytes of HNC patients undergoing RT with subsequent fractions. Cisplatin-based chemoradiation is the superior method of treatment intensification radio-biologically proven by higher DC yield.

A novel technique for invasive aortic valve pressure gradient measurement using a 6 Fr Swan-Ganz catheter: a case series.

BACKGROUND: Simultaneous left ventricular (LV) and aortic (Ao) pressure gradient assessment has been rendered challenging since the recall of the Langston catheter. Here we describe a simple method for simultaneous LV and Ao pressure gradient assessment using a Swan-Ganz catheter. CASE SUMMARY: We describe two cases where assessment of simultaneous left ventricle and Ao valve gradients was done using a Swan-Ganz catheter to assess the degree of Ao stenosis and dynamic LV outflow obstruction. DISCUSSION: Using Swan-Ganz catheter assessment of simultaneous left ventricle and Ao valve gradients can simplify the procedure with reduced cost and increased patient safety.

Novel targeted therapies for metastatic breast cancer.

Metastatic breast cancer (mBC) continues to be a leading cause of cancer-related death in women. Even though mortality rates have improved over recent years, the 5-year survival rate of advanced BC is still at only 27%. As researchers and clinicians attempt to tackle this challenge, there has been extensive research and many trials studying treatment options for BC patients with metastatic disease, with numerous new therapies being discovered as a result. We review the most pertinent novel agents to enter the scope of BC treatment, including CDK4/6 inhibitors, PI3K inhibitors, mTOR inhibitors, immunotherapy, PARP inhibitors, and more.

Peripheral Arterial Disease in Women: The Gender Effect.

Peripheral arterial disease (PAD) is a common atherosclerotic disease approximately affecting 8.5 million Americans above age 40 and is associated with significant functional impairment, morbidity and mortality from both cardiovascular and non-cardiovascular causes. PAD has increasing prevalence in females contrary to previous findings. Compared to men, women with PAD are more asymptomatic or have atypical symptoms. Women with PAD have increased quality of life impairment, increased risk of depression and increased cardiovascular mortality. The intent of this review is to provide an update on gender differences in PAD that can help in timely diagnosis and appropriate management through intensive cardiovascular risk factor modification, exercise program and guideline directed therapy to improve cardiovascular outcomes.

Dual versus triple antithrombotic therapy in patients undergoing percutaneous coronary intervention-meta-analysis and meta-regression.

BACKGROUND: Anti-thrombotic regimen in patients on long term anticoagulation requiring coronary intervention remains a clinical challenge. METHODS: We performed a meta-analysis of observational studies and randomized controlled trials comparing outcomes of triple therapy (dual antiplatelet therapy and anticoagulant) with dual therapy (P2Y12 inhibitor and anticoagulant) in patients on long-term anticoagulants after percutaneous coronary intervention (PCI). Major bleeding was the primary outcome. RESULTS: Three observational studies and 3 randomized controlled trials with a total of 6654 patients met our selection criteria. At a mean follow up of 12.5 months major bleeding was lower in dual therapy cohort compared to triple therapy (2.2% vs 5.2%, RR 0.60, 95% CI 0.44-0.81, P = 0.001). No difference was observed between the two groups for major adverse cardiac events (11.8% vs 13.0%, RR 1.03, CI 0.79-1.34, P = 0.85), all-cause mortality (3.9% vs 5.6%, RR 0.94, CI 0.65-1.36, P = 0.76), myocardial infarction (3.7% vs 3.9%, RR 1.12, CI 0.83-1.50, P = 0.47), target vessel revascularization (6.8% vs 7.1%, RR 1.12, CI 0.72-1.74, P = 0.60), thromboembolic events (1.3% vs 1.6%, RR 0.95, CI 0.55-1.64, P = 0.85) and stent thrombosis (1.3% vs 1.4%, RR1.36, CI 0.84-2.21, P = 0.21). CONCLUSION: For patients undergoing PCI and requiring long term anticoagulation, a strategy of P2Y12 inhibitor plus anticoagulant confers a benefit of less major bleeding with no difference in major adverse cardiac events, mortality, myocardial infarction, target vessel revascularization, stent thrombosis or thromboembolism compared with triple therapy.

Triangulated Wireframe Structures Assembled Using Single-Stranded DNA Tiles.

The field of structural DNA nanotechnology offers a wide range of design strategies with which to build structures with a desired aspect ratio, size, and shape. Compared with traditional close-packed DNA structures, triangulated wireframe structures require less material per surface or volume unit and improve the stability in biologically relevant conditions due to the reduced electrostatic repulsion. Herein, we expand the design space of the DNA single-stranded tile method to cover a range of anisotropic, finite, triangulated wireframe structures as well as a number of one-dimensional crystalline assemblies. These structures are composed of six-arm junctions with a single double helix as connecting edges that assemble in physiologically relevant salinities. For a reliable folding of the structures, single-stranded spacers 2-4 nucleotides long have to be introduced in the junction connecting neighboring arms. Coarse-grained molecular dynamics simulations using the oxDNA model suggests that the spacers prevent the stacking of DNA helices, thereby facilitating the assembly of planar geometries.

Mentoring in Surgery-Mentor, Parshuram, Dronacharya, Krishan.

Success in any profession has no well-defined predictors. Knowledge, skills, training, and talent come in plenty but fail at times to achieve the universal goal of success. Some attribute it to luck. Apart from the tangible ingredients of a successful career, the intangibles like luck or something ill-defined is a real challenge. The intangibles seem like a chasm, an abyss, or a phantom obstacle. Presence of a guiding spirit who can handhold you to overcome these is essential for success. The aim of a professional is to learn, earn, and yearn for creativity. Practice of surgery is an ideal career to pursue the learning, earning, and yearning. More than any other profession, the guiding handholding spirit is required in surgical profession, the concept of mentoring. Originating from the Greco-Roman times when kind Odysseus left his son Telemachus under the care of his friend, mentor, it has become a universal defining necessity for a successful career in surgery. Indian history replete with such examples of mentorship, good as in the case of Dronacharya to Kaurvas but bad as denied by an able, competent, aspiring student like Eklavya. In the medical profession, there are very few Indian role models of mentorship. One name that comes to our mind is Dr. Krishan Mahajan. The more said is less revealed about him. "Knife before wife" was his commonly spoken advice to all who sought his mentorship. "Hard work is not easy but it is fair" so said a famous boxer, Larry Holmes. It is more than true for our profession as it is better to prepare and prevent, rather than repair and repent.

Optimum Antithrombotic Therapy in Patients Requiring Long-Term Anticoagulation and Undergoing Percutaneous Coronary Intervention.

Management of patients on long-term anticoagulation requiring percutaneous coronary intervention is challenging. Triple therapy with oral anticoagulant and dual antiplatelet therapy is the standard of care. However, there is no strong evidence to support this strategy. There is emerging data regarding the safety and efficacy of dual therapy with oral anticoagulant and single antiplatelet therapy in these patients. In this comprehensive review we highlight available evidence regarding various antithrombotic regimens' efficacy and safety in patient with coronary artery disease undergoing percutaneous coronary intervention with long-term anticoagulation therapy requirements.

Structural Transformation of Wireframe DNA Origami via DNA Polymerase Assisted Gap-Filling.

The programmability of DNA enables constructing nanostructures with almost any arbitrary shape, which can be decorated with many functional materials. Moreover, dynamic structures can be realized such as molecular motors and walkers. In this work, we have explored the possibility to synthesize the complementary sequences to single-stranded gap regions in the DNA origami scaffold cost effectively by a DNA polymerase rather than by a DNA synthesizer. For this purpose, four different wireframe DNA origami structures were designed to have single-stranded gap regions. This reduced the number of staple strands needed to determine the shape and size of the final structure after gap filling. For this, several DNA polymerases and single-stranded binding (SSB) proteins were tested, with T4 DNA polymerase being the best fit. The structures could be folded in as little as 6 min, and the subsequent optimized gap-filling reaction was completed in less than 3 min. The introduction of flexible gap regions results in fully collapsed or partially bent structures due to entropic spring effects. Finally, we demonstrated structural transformations of such deformed wireframe DNA origami structures with DNA polymerases including the expansion of collapsed structures and the straightening of curved tubes. We anticipate that this approach will become a powerful tool to build DNA wireframe structures more material-efficiently, and to quickly prototype and test new wireframe designs that can be expanded, rigidified, or mechanically switched. Mechanical force generation and structural transitions will enable applications in structural DNA nanotechnology, plasmonics, or single-molecule biophysics.

Safety and efficacy of second-generation drug-eluting stents compared with bare-metal stents: An updated meta-analysis and regression of 9 randomized clinical trials.

The efficacy of second-generation drug-eluting stents (DES; eg, everolimus and zotarolimus) compared with bare-metal stents (BMS) in patients undergoing percutaneous coronary intervention was challenged recently by new evidence from large clinical trials. Thus, we aimed to conduct an updated systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating the efficacy and safety of second-generation DES compared with BMS. Electronic databases were systematically searched for all RCTs comparing second-generation DES with BMS and reporting clinical outcomes. The primary efficacy outcome was major adverse cardiac events (MACE); the primary safety outcome was definite stent thrombosis. The DerSimonian and Laird method was used for estimation of summary risk ratios (RR). A total of 9 trials involving 17 682 patients were included in the final analysis. Compared with BMS, second-generation DES were associated with decreased incidence of MACE (RR: 0.78, 95% confidence interval [CI]: 0.69-0.88), driven by the decreased incidence of myocardial infarction (MI) (RR: 0.67, 95% CI: 0.48-0.95), target-lesion revascularization (RR: 0.47, 95% CI: 0.42-0.53), definite stent thrombosis (RR: 0.57, 95% CI: 0.41-0.78), and definite/probable stent thrombosis (RR: 0.54, 95% CI: 0.38-0.80). The incidence of all-cause mortality was similar between groups (RR: 0.94, 95% CI: 0.79-1.10). Meta-regression showed lower incidences of MI with DES implantation in elderly and diabetic patients (P = 0.026 and P < 0.0001, respectively). Compared with BMS, second-generation DES appear to be associated with a lower incidence of MACE, mainly driven by lower rates of target-lesion revascularization, MI, and stent thrombosis. However, all-cause mortality appears similar between groups.

DNA-encircled lipid bilayers.

Lipid bilayers and lipid-associated proteins play crucial roles in biology. As in vivo studies and manipulation are inherently difficult, membrane-mimetic systems are useful for the investigation of lipidic phases, lipid-protein interactions, membrane protein function and membrane structure in vitro. In this work, we describe a route to leverage the programmability of DNA nanotechnology and create DNA-encircled bilayers (DEBs). DEBs are made of multiple copies of an alkylated oligonucleotide hybridized to a single-stranded minicircle, in which up to two alkyl chains per helical turn point to the inside of the toroidal DNA ring. When phospholipids are added, a bilayer is observed to self-assemble within the ring such that the alkyl chains of the oligonucleotides stabilize the hydrophobic rim of the bilayer to prevent formation of vesicles and support thermotropic lipid phase transitions. The DEBs are completely free of protein and can be synthesized from commercially available components using routine equipment. The diameter of DEBs can be varied in a predictable manner. The well-established toolbox from structural DNA nanotechnology, will ultimately enable the rational design of DEBs so that their size, shape or functionalization can be adapted to the specific needs of biophysical investigations of lipidic phases and the properties of membrane proteins embedded into DEB nanoparticle bilayers.

Cryptogenic Stroke and Patent Foramen Ovale.

Nearly one-half of patients with cryptogenic stroke have a patent foramen ovale (PFO). The dilemma of whether to close these PFOs percutaneously, in an effort to reduce the risk of recurrent paradoxical embolism, has been a matter of ongoing debate for more than a decade. Early randomized clinical trials failed to demonstrate a significant benefit of percutaneous PFO closure for secondary prevention of cryptogenic stroke in an intention-to-treat analysis. The long-term follow-up data from the RESPECT trial and 2 new randomized trials (CLOSE and REDUCE) have clarified these findings. They showed that with good patient selection, transcatheter PFO closure significantly reduces the risk of recurrent stroke compared with medical therapy in patients with cryptogenic stroke, with no increased risk of serious adverse events or influence on major bleeding.

Influence of Atrial Fibrillation on Outcomes in Patients Who Underwent Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

Atrial fibrillation (AF) is a common co-morbidity among patients presenting with acute ST-segment elevation myocardial infarction (STEMI). Previously, small studies have reported an association between AF and poorer outcomes among patients with STEMI. We performed this study to investigate the impact of AF on in-hospital outcomes in patients with STEMI treated with primary percutaneous coronary intervention (PPCI) using a large national database. The study population constituted of patients 18 years and older with a primary discharge diagnosis of STEMI and who underwent PPCI. Using a 2:1 matching protocol, matched groups of patients with AF (N = 24,680) and without (N = 49,198) were developed. Among 1,493,859 patients with STEMI who underwent PPCI, 129,354 patients (8.7%) had AF. In the propensity-matched cohort, adjusted in-hospital mortality was significantly higher for patients with AF compared with patients with no AF (10.3% vs 9.4%) (adjusted odds ratio [OR] 1.10; confidence interval [CI] 1.06 to 1.16; p <0.0001). Patients with AF were also at higher risk of heart failure, cardiogenic shock, acute stroke, acute kidney injury, vascular complications, need for blood transfusion, and a composite outcome of gastrointestinal and retroperitoneal bleeding. Patients with AF were less likely to be treated with drug-eluting stent compared with patients without AF (51.4% vs 56.6%) (adjusted OR 0.81; CI 0.79 to 0.84; p <0.001). Among patients presenting with STEMI and who underwent PPCI, AF is present in about 8% of patients. In a propensity-matched analysis using a large national database, AF was found to be independently associated with a higher risk of in-hospital mortality and of other complications in these patients.