Over-expansion capacity and stent design model: an update with contemporary DES platforms

© 2016 The AuthorsBackground Previously, we examined the difference in stent designs across different sizes for six widely used Drug Eluting Stents (DESs). Although stent post-dilatation to larger diameter is commonly done, typically in the setting of long tapering segment or left-main PCI, there is an increasing recognition that information with regard to the different stent model designs has a critical impact on overexpansion results. This study aims to provide an update on stent model designs for contemporary DES platforms as well as test overexpansion results under with oversized post-dilatation. Methods and results We studied 6 different contemporary commercially available DES platforms: Synergy, Xience Xpedition, Ultimaster, Orsiro, Resolute Onyx and Biomatrix Alpha. We investigated for each platform the difference in stent designs across different sizes and results obtained after post-expansion with larger balloon sizes. The stents were deployed at nominal diameter and subsequently over expanded using increasingly large post dilatation balloon sizes (4.0, 5.0 and 6.0 mm at 14ATM). Light microscopy was used to measure the changes in stent geometry and lumen diameter after over-expansion. For each respective DES platform, the MLD observed after overexpansion of the largest stent size available with a 6.0 mm balloon was 5.7 mm for Synergy, 5.6 mm for Xience, 5.2 mm for Orsiro, 5.8 mm for Ultimaster, 5.5 mm for 4 mm Onyx (5.9 mm for the 5 mm XL size) and 5.8 mm for BioMatrix Chroma. Conclusion This update presents valuable novel insights that may be helpful for careful selection of stent size for contemporary DES based on model designs. Such information is especially critical in left main bifurcation stenosis treatment where overexpansion to larger oversized diameter may be required to ensure full stent apposition

Identification and functional validation of FDA-approved positive and negative modulators of the mitochondrial calcium uniporter

The mitochondrial calcium uniporter (MCU), the highly selective channel responsible for mitochondrial Ca2+ entry, plays important roles in physiology and pathology. However, only few pharmacological compounds directly and selectively modulate its activity. Here, we perform high-throughput screening on a US Food and Drug Administration (FDA)-approved drug library comprising 1,600 compounds to identify molecules modulating mitochondrial Ca2+ uptake. We find amorolfine and benzethonium to be positive and negative MCU modulators, respectively. In agreement with the positive effect of MCU in muscle trophism, amorolfine increases muscle size, and MCU silencing is sufficient to blunt amorolfine-induced hypertrophy. Conversely, in the triple-negative breast cancer cell line MDA-MB-231, benzethonium delays cell growth and migration in an MCU-dependent manner and protects from ceramide-induced apoptosis, in line with the role of mitochondrial Ca2+ uptake in cancer progression. Overall, we identify amorolfine and benzethonium as effective MCU-targeting drugs applicable to a wide array of experimental and disease conditions

The Uncertainty Principle in the Presence of Quantum Memory

The uncertainty principle, originally formulated by Heisenberg, dramatically illustrates the difference between classical and quantum mechanics. The principle bounds the uncertainties about the outcomes of two incompatible measurements, such as position and momentum, on a particle. It implies that one cannot predict the outcomes for both possible choices of measurement to arbitrary precision, even if information about the preparation of the particle is available in a classical memory. However, if the particle is prepared entangled with a quantum memory, a device which is likely to soon be available, it is possible to predict the outcomes for both measurement choices precisely. In this work we strengthen the uncertainty principle to incorporate this case, providing a lower bound on the uncertainties which depends on the amount of entanglement between the particle and the quantum memory. We detail the application of our result to witnessing entanglement and to quantum key distribution.Comment: 5 pages plus 12 of supplementary information. Updated to match the journal versio

Transparent dense sodium

Under pressure, metals exhibit increasingly shorter interatomic distances. Intuitively, this response is expected to be accompanied by an increase in the widths of the valence and conduction bands and hence a more pronounced free-electron-like behaviour. But at the densities that can now be achieved experimentally, compression can be so substantial that core electrons overlap. This effect dramatically alters electronic properties from those typically associated with simple free-electron metals such as lithium and sodium, leading in turn to structurally complex phases and superconductivity with a high critical temperature. But the most intriguing prediction - that the seemingly simple metals Li and Na will transform under pressure into insulating states, owing to pairing of alkali atoms - has yet to be experimentally confirmed. Here we report experimental observations of a pressure-induced transformation of Na into an optically transparent phase at 200 GPa (corresponding to 5.0-fold compression). Experimental and computational data identify the new phase as a wide bandgap dielectric with a six-coordinated, highly distorted double-hexagonal close-packed structure. We attribute the emergence of this dense insulating state not to atom pairing, but to p-d hybridizations of valence electrons and their repulsion by core electrons into the lattice interstices. We expect that such insulating states may also form in other elements and compounds when compression is sufficiently strong that atomic cores start to overlap strongly.Comment: Published in Nature 458, 182-185 (2009

Probing empirical contact networks by simulation of spreading dynamics

Disease, opinions, ideas, gossip, etc. all spread on social networks. How these networks are connected (the network structure) influences the dynamics of the spreading processes. By investigating these relationships one gains understanding both of the spreading itself and the structure and function of the contact network. In this chapter, we will summarize the recent literature using simulation of spreading processes on top of empirical contact data. We will mostly focus on disease simulations on temporal proximity networks -- networks recording who is close to whom, at what time -- but also cover other types of networks and spreading processes. We analyze 29 empirical networks to illustrate the methods

Molecular Refinement of Clinical Staging in Hepatocellular Carcinoma Patients Evaluated for Potentially Curative Therapies

Abstract: Aim: VEGF and AFP mRNA determinations in the blood are promising prognostic factors for patients with HCC. This study explores their potential prognostic synergy in a cohort of HCC patients evaluated for potentially curative therapies. Methods: One hundred twenty-four patients with a diagnosis of HCC were prospectively enrolled in the study. Inclusion criteria were: (a) histological diagnosis of HCC and assessment of tumour grade and (b) determination of AFP mRNA status and VEGF levels in the blood before therapy. Results: At baseline evaluation, 40% of the study group had AFP mRNA in the blood (AFP mRNA positive), and 35% had VEGF > 23 pg ml(-1) (VEGF positive). Surgery was performed in 58 patients (47%), 54 (43%) had tumour ablation, and 12 had chemoembolisation (10%). Median follow-up and survival of the study group were 19 and 26 months (range, 1 to 60), respectively. The association of AFP mRNA and VEGF proved to be prognostically more accurate than their single use in discriminating the risk of death (ROC curve analysis) and survival probability (Cox analysis). In particular, we identified 3 main molecular stages (p < 0,0001): both negative (3-year survival = 63%), one positive (3-year survival = 40%), both positive (3-year survival = 16%). Multivariate analysis identified BCLC staging, surgery, and molecular staging as the most significant survival variables. Conclusions: The preoperative determination of AFP mRNA status and VEGF may potentially refine the prognostic evaluation of HCC patients and improve the selection process for potentially curative therapies

High prevalence of high risk human papillomavirus-capsid antibodies in human immunodeficiency virus-seropositive men: a serological study

BACKGROUND: Serological study of human papillomavirus (HPV)-antibodies in order to estimate the HPV-prevalence as risk factor for the development of HPV-associated malignancies in human immunodeficiency virus (HIV)-positive men. METHODS: Sera from 168 HIV-positive men and 330 HIV-negative individuals (including 198 controls) were tested using a direct HPV-ELISA specific to HPV-6, -11, -16, -18, -31 and bovine PV-1 L1-virus-like particles. Serological results were correlated with the presence of HPV-associated lesions, the history of other sexually transmitted diseases (STD) and HIV classification groups. RESULTS: In HIV-negative men low risk HPV-antibodies were prevailing and associated with condylomatous warts (25.4%). Strikingly, HIV-positive men were more likely to have antibodies to the high-risk HPV types -16, -18, -31, and low risk antibodies were not increased in a comparable range. Even those HIV-positive heterosexual individuals without any HPV-associated lesions exhibited preferentially antibody responses to the oncogenic HPV-types (cumulative 31.1%). The highest antibody detection rate (88,8%) was observed within the subgroup of nine HIV-positive homosexual men with anogenital warts. Three HIV-positive patients had HPV-associated carcinomas, in all of them HPV-16 antibodies were detected. Drug use and mean CD4-cell counts on the day of serologic testing had no influence on HPV-IgG antibody prevalence, as had prior antiretroviral therapy or clinical category of HIV-disease. CONCLUSION: High risk HPV-antibodies in HIV-infected and homosexual men suggest a continuous exposure to HPV-proteins throughout the course of their HIV infection, reflecting the known increased risk for anogenital malignancies in these populations. The extensive increase of high risk antibodies (compared to low risk antibodies) in HIV-positive patients cannot be explained by differences in exposure history alone, but suggests defects of the immunological control of oncogenic HPV-types. HPV-serology is economic and can detect past or present HPV-infection, independently of an anatomical region. Therefore HPV-serology could help to better understand the natural history of anogenital HPV-infection in HIV-positive men in the era of antiretroviral therapy

Practice makes perfect: the development of a medical student-led crowdsourced question bank for self-study in undergraduate medical education

Implication Statement The development of multiple-choice questions (MCQs) for undergraduate medical education study purposes is resource intensive. Commercially available question banks are typically expensive, only available in English, and may not be aligned with medical school learning objectives. Here, we introduce The Ottawa Question Bank: a student-led, bilingual study resource curated to a Canadian undergraduate medicine curriculum (www.theottawaquestionbank.ca). In total, 205 medical students wrote and edited 4438 original MCQs linked to objectives from the University of Ottawa undergraduate medical education curriculum. The project has received positive feedback from both developers and users. Our experience suggests that involving medical students in MCQ development is feasible and can result in the rapid creation of a low-cost, high-quality study resource curated to a program’s learning objectives. The platform outlined here can be used as a model for other medical schools and professional degree programs to develop their own question banks, including pharmacy, dentistry, nursing, and physiotherapy. Interested programs are encouraged to contact our team for collaborative opportunities

The Disrupt CAD II Study

BACKGROUND: The feasibility of intravascular lithotripsy (IVL) for modification of severe coronary artery calcification (CAC) was demonstrated in the Disrupt CAD I study (Disrupt Coronary Artery Disease). We next sought to confirm the safety and effectiveness of IVL for these lesions. METHODS: The Disrupt CAD II study was a prospective multicenter, single-arm post-approval study conducted at 15 hospitals in 9 countries. Patients with severe CAC with a clinical indication for revascularization underwent vessel preparation for stent implantation with IVL. The primary end point was in-hospital major adverse cardiac events (cardiac death, myocardial infarction, or target vessel revascularization). An optical coherence tomography substudy was performed to evaluate the mechanism of action of IVL, quantifying CAC characteristics and calcium plaque fracture. Independent core laboratories adjudicated angiography and optical coherence tomography, and an independent clinical events committee adjudicated major adverse cardiac events. RESULTS: Between May 2018 and March 2019, 120 patients were enrolled. Severe CAC was present in 94.2% of lesions. Successful delivery and use of the IVL catheter was achieved in all patients. The post-IVL angiographic acute luminal gain was 0.83±0.47 mm, and residual stenosis was 32.7±10.4%, which further decreased to 7.8±7.1% after drug-eluting stent implantation. The primary end point occurred in 5.8% of patients, consisting of 7 non-Q-wave myocardial infarctions. There was no procedural abrupt closure, slow or no reflow, or perforations. In 47 patients with post-percutaneous coronary intervention optical coherence tomography, calcium fracture was identified in 78.7% of lesions with 3.4±2.6 fractures per lesion, measuring 5.5±5.0 mm in length. CONCLUSIONS: In patients with severe CAC who require coronary revascularization, IVL was safely performed with high procedural success and minimal complications and resulted in substantial calcific plaque fracture in most lesions. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03328949

Adhesions due to peritoneal carcinomatosis caused by a renal carcinoma leading to mechanical gastric outlet obstruction: a case report

<p>Abstract</p> <p>Introduction</p> <p>Gastric outlet obstruction is a clinical syndrome caused by a variety of mechanical obstructions. Peptic ulcer disease used to be responsible for most gastric outlet obstruction, but in the last 40 years the prevalence of malignant tumors has risen significantly. Adhesive disease is an infrequent and insidious cause of mechanical gastric outlet obstruction.</p> <p>Case presentation</p> <p>We report the case of a 78-year-old Caucasian man who had a clinical history of a right nephrectomy for malignancy three years earlier and who was admitted for a severe gastric outlet obstruction (score of 1) confirmed both by an upper endoscopy and by a fluoroscopic view after contrast injection. A computed tomography scan and a laparotomy, with omental biopsies, showed a peritoneal carcinomatosis with the development of abdominal adhesions that prompted an abnormal gastric rotation around the perpendicular axis of his antrum with a dislocation in the empty space of his right kidney. Symptoms disappeared after surgical bypass through a gastrojejunostomy.</p> <p>Conclusions</p> <p>Our patient experienced a very rare complication characterized by the development of adhesions due to peritoneal carcinomatosis caused by a renal carcinoma treated with nephrectomy. These adhesions prompted an abnormal dislocation of his antrum, as an internal hernia, in the empty space of his right kidney.</p