Stenting of common iliac vein obstructions combined with regional thrombolysis and thrombectomy in acute deep vein thrombosis

OBJECTIVES: To evaluate the efficacy of stent placement after infrainguinal loco-regional thrombolysis and iliac thrombectomy (surgical TT) of acute deep vein thrombosis (DVT) in patients with May-Thurner-Syndrome. MATERIAL AND METHODS: We retrospectively analysed a group of 11 patients (9 women) (mean age 34 years, range 16-64 years) with surgical TT and additional intra-operative stenting due to compression of the common iliac vein. Patients underwent venography to demonstrate outflow patency after surgical TT, and to identify any obstruction at the level of the left-sided common iliac vein ("Beckenvenen-Sporn"). Obstruction at the level of arterial crossing was treated using Wallstents placed via an introducer sheath from the inguinal access site. Stents were fully deployed using balloons adjusted to the size of vein. Patients were treated with oral anticoagulants for 6 months, and followed using duplex ultrasonography. RESULTS: Technical success defined as complete vein patency and normal valve function was documented in all 11 patients. One patient needed early stent extension due to residual stenosis. At 6 months follow-up one patient (9%) had an asymptomatic occlusion of the stented common iliac vein. In all 11/11 (100%) patients the femoral segment was found to be patent, and in 1/11 (9%) there was mild reflux with few clinical symptoms of post-thrombotic syndrome. The calculated cumulative primary patency rate for venous iliac stents was 82%, and assisted patency rate was 91%, which remained unchanged over a mean follow-up of 22 months. CONCLUSION: Combining surgical TT and stenting of common iliac vein obstructions in DVT is safe, effective, and results in a acceptable venous patency.

Safety and feasibility of percutaneous closure of patent foramen ovale without intra-procedural echocardiography in 825 patients

BACKGROUND: Percutaneous closure of patent foramen ovale (PFO) is generally performed using intra-procedural guidance by transoesophageal (TEE) or intracardiac (ICE) echocardiography. While TEE requires sedation or general anaesthesia, ICE is costly and adds incremental risk, and both imaging modalities lengthen the procedure. METHODS: A total of 825 consecutive patients (age 51 +/- 13 years; 58% male) underwent percutaneous PFO closure solely under fluoroscopic guidance, without intra-procedural echocardiography. The indications for PFO closure were presumed paradoxical embolism in 698 patients (95% cerebral, 5% other locations), an embolic event with concurrent aetiologies in 47, diving in 51, migraine headaches in 13, and other reasons in 16. An atrial septal aneurysm was associated with the PFO in 242 patients (29%). RESULTS: Permanent device implantation failed in two patients (0.2%). There were 18 procedural complications (2.2%), including embolization of the device or parts of it in five patients with successful percutaneous removal in all cases, air embolism with transient symptoms in four patients, pericardial tamponade requiring pericardiocentesis in one patient, a transient ischaemic attack with visual symptoms in one patient, and vascular access site problems in seven patients. There were no long-term sequelae. Contrast TEE at six months showed complete abolition of right-to-left shunt via PFO in 88% of patients, whereas a minimal, moderate or large residual shunt persisted in 7%, 3%, and 2%, respectively. CONCLUSIONS: This study confirms the safety and feasibility of percutaneous PFO closure without intra-procedural echocardiographic guidance in a large cohort of consecutive patients.

The 2011-12 pilot European Sentinel Registry of Transcatheter Aortic Valve Implantation: in-hospital results in 4,571 patients

AIMS The aim of this prospective multinational registry is to assess and identify predictors of in-hospital outcome and complications of contemporary TAVI practice. METHODS AND RESULTS The Transcatheter Valve Treatment Sentinel Pilot Registry is a prospective independent consecutive collection of individual patient data entered into a web-based case record form (CRF) or transferred from compatible national registries. A total of 4,571 patients underwent TAVI between January 2011 and May 2012 in 137 centres of 10 European countries. Average age was 81.4±7.1 years with equal representation of the two sexes. Logistic EuroSCORE (20.2±13.3), access site (femoral approach: 74.2%), type of anaesthesia and duration of hospital stay (9.3±8.1 days) showed wide variations among the participating countries. In-hospital mortality (7.4%), stroke (1.8%), myocardial infarction (0.9%), major vascular complications (3.1%) were similar in the SAPIEN XT and CoreValve (p=0.15). Mortality was lower in transfemoral (5.9%) than in transapical (12.8%) and other access routes (9.7%; p<0.01). Advanced age, high logistic EuroSCORE, pre-procedural ≥grade 2 mitral regurgitation and deployment failure predicted higher mortality at multivariate analysis. CONCLUSIONS Increased operator experience and the refinement of valve types and delivery catheters may explain the lower rate of mortality, stroke and vascular complications than in historical studies and registries.

Percutaneous left-ventricular support with the Impella-2.5-assist device in acute cardiogenic shock: results of the Impella-EUROSHOCK-registry

BACKGROUND Acute cardiogenic shock after myocardial infarction is associated with high in-hospital mortality attributable to persisting low-cardiac output. The Impella-EUROSHOCK-registry evaluates the safety and efficacy of the Impella-2.5-percutaneous left-ventricular assist device in patients with cardiogenic shock after acute myocardial infarction. METHODS AND RESULTS This multicenter registry retrospectively included 120 patients (63.6±12.2 years; 81.7% male) with cardiogenic shock from acute myocardial infarction receiving temporary circulatory support with the Impella-2.5-percutaneous left-ventricular assist device. The primary end point evaluated mortality at 30 days. The secondary end point analyzed the change of plasma lactate after the institution of hemodynamic support, and the rate of early major adverse cardiac and cerebrovascular events as well as long-term survival. Thirty-day mortality was 64.2% in the study population. After Impella-2.5-percutaneous left-ventricular assist device implantation, lactate levels decreased from 5.8±5.0 mmol/L to 4.7±5.4 mmol/L (P=0.28) and 2.5±2.6 mmol/L (P=0.023) at 24 and 48 hours, respectively. Early major adverse cardiac and cerebrovascular events were reported in 18 (15%) patients. Major bleeding at the vascular access site, hemolysis, and pericardial tamponade occurred in 34 (28.6%), 9 (7.5%), and 2 (1.7%) patients, respectively. The parameters of age >65 and lactate level >3.8 mmol/L at admission were identified as predictors of 30-day mortality. After 317±526 days of follow-up, survival was 28.3%. CONCLUSIONS In patients with acute cardiogenic shock from acute myocardial infarction, Impella 2.5-treatment is feasible and results in a reduction of lactate levels, suggesting improved organ perfusion. However, 30-day mortality remains high in these patients. This likely reflects the last-resort character of Impella-2.5-application in selected patients with a poor hemodynamic profile and a greater imminent risk of death. Carefully conducted randomized controlled trials are necessary to evaluate the efficacy of Impella-2.5-support in this high-risk patient group.

Assessing the cardiology community position on transradial intervention and the use of bivalirudin in patients with acute coronary syndrome undergoing invasive management: results of an EAPCI survey

AIMS Our aim was to report on a survey initiated by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) collecting the opinion of the cardiology community on the invasive management of acute coronary syndrome (ACS), before and after the MATRIX trial presentation at the American College of Cardiology (ACC) 2015 Scientific Sessions. METHODS AND RESULTS A web-based survey was distributed to all individuals registered on the EuroIntervention mailing list (n=15,200). A total of 572 and 763 physicians responded to the pre- and post-ACC survey, respectively. The radial approach emerged as the preferable access site for ACS patients undergoing invasive management with roughly every other responder interpreting the evidence for mortality benefit as definitive and calling for a guidelines upgrade to class I. The most frequently preferred anticoagulant in ACS patients remains unfractionated heparin (UFH), due to higher costs and greater perceived thrombotic risks associated with bivalirudin. However, more than a quarter of participants declared the use of bivalirudin would increase after MATRIX. CONCLUSIONS The MATRIX trial reinforced the evidence for a causal association between bleeding and mortality and triggered consensus on the superiority of the radial versus femoral approach. The belief that bivalirudin mitigates bleeding risk is common, but UFH still remains the preferred anticoagulant based on lower costs and thrombotic risks.

Comparação entre a técnica femoral com dispositivo de hemostasia e a técnica radial em pacientes submetidos à estratégia invasiva precoce

A via de acesso arterial é um importante sítio de complicações após a realização de procedimentos coronários invasivos. Dentre as estratégias para a redução de complicações vasculares, encontra-se estabelecida a eficácia da técnica radial. Os dispositivos de oclusão vascular propiciam maior conforto ao paciente, reduzindo o tempo de hemostasia e repouso no leito. Entretanto, a inconsistência de dados comprovando sua segurança limita sua adoção rotineira como estratégia para redução de complicações vasculares, requerendo evidências de estudos randomizados com metodologia adequada. O objetivo deste estudo foi comparar a incidência de complicações no sítio de punção arterial entre a técnica radial e a técnica femoral com utilização de Angio-Seal em pacientes com síndrome coronariana aguda sem supradesnível do segmento ST submetidos à estratégia invasiva precoce. Trata-se de um ensaio clínico unicêntrico, de não inferioridade, no qual duzentos e quarenta pacientes foram randomizados para a técnica radial ou técnica femoral com utilização de Angio-Seal. O objetivo primário foi a ocorrência de complicações no sítio de punção arterial até 30 dias após o procedimento, incluindo sangramento grave, hematoma >= 5 cm, hematoma retroperitoneal, síndrome compartimental, pseudoaneurisma, fístula arteriovenosa, infecção, isquemia de membro, oclusão arterial, lesão de nervo adjacente ou necessidade de reparo vascular cirúrgico. Em relação às características demográficas e clínicas, houve diferença apenas quanto ao gênero, com presença maior de pacientes do sexo feminino no grupo radial (33,3% versus 20,0%, p=0,020). Não se observaram diferenças entre os grupos quanto ao diagnóstico de admissão, alterações isquêmicas presentes no eletrocardiograma, elevação de marcadores de necrose miocárdica ou escores de risco, bem como quanto à farmacoterapia antitrombótica adjunta e características da intervenção coronária percutânea. A hemostasia foi obtida na totalidade dos procedimentos do grupo radial com a utilização da pulseira compressora seletiva TR Band e em 95% dos procedimentos realizados pela técnica femoral com o Angio-Seal (p=0,029). Exceto pela maior incidência de oclusão arterial no grupo radial comparado ao femoral, não houve diferenças entre os demais desfechos analisados. Segundo o teste de não inferioridade para complicações na via de acesso arterial aos 30 dias, verificou-se que a utilização do Angio-Seal não produziu resultados inferiores ao acesso radial, considerando-se a margem de 15% (12,5% versus 13,3%, diferença -0,83%, IC 95% -9,31 - 7,65, p para não inferioridade <0,001). Os resultados principais deste estudo demonstram que, em uma população de pacientes com diagnóstico de síndrome coronariana aguda sem supradesnível do segmento ST, submetida à estratificação de risco invasiva, a utilização do dispositivo de oclusão vascular Angio-Seal confere ao procedimento efetivado pelo acesso femoral inferioridade na incidência de complicações no sítio de punção arterial aos 30 dias quando comparado ao acesso radial.

Avaliação de qualidade da unidade de diálise no Hospital Universitário Onofre Lopes - HUOL

Over the years there has been a broader definition of the term health. At the same time it was found also an evolution of the concept of health care which in turn has led to changes in the approach to delivery of health services and hence in its management. In this regard, currently the nephrology services have been searching for quality technical and social need. In view of these innovations and the quest for quality, it elaborated the general objective: to develop a quality assessment protocol for dialysis service Onofre Lopes University Hospital. It is an intervention project effected through an action research, which consisted of 4 steps. Initially was identified through a literature search in scientific literature, which quality indicators would apply to a dialysis unit being selected as follows: infection rate in hemodialysis access site, microbiological control of water used for hemodialysis and Index User satisfaction. Through critical reflection on the theme researched in the previous step, it was drawn up three data collection instruments, interview form type, applied between the months of October and November 2015. In addition to the information obtained, also made up of the use of information retrieval technique. The results were organized in graphs and tables and analyzed using qualitative and exploratory technical approach. Then a reflective analysis of the data obtained and the diagnosis of reality studied was traced and confronted with the literature was performed. The data produced in this study revealed that the Dialysis Unit of HUOL is much to be desired, considering that some weaknesses have been identified in its structure. Faced with this finding have been proposed, as a contribution and aiming to guide the development of future actions, suggestions for improvement that should be implemented and monitored to be assured overcoming these difficulties, allowing an appropriate organizational restructuring, and resulting in improved service public offered. It was concluded that for hemodialysis treatment results are achieved and positive, it is necessary to have physical structure and adequate infrastructure, multidisciplinary team specialized, trained and in sufficient quantity, well designed processes for professionals to have standards to be followed decreasing the chance to err, and a risk management system to detect and control situations that endanger patient safety.

Avaliação de qualidade da unidade de diálise no Hospital Universitário Onofre Lopes - HUOL

Over the years there has been a broader definition of the term health. At the same time it was found also an evolution of the concept of health care which in turn has led to changes in the approach to delivery of health services and hence in its management. In this regard, currently the nephrology services have been searching for quality technical and social need. In view of these innovations and the quest for quality, it elaborated the general objective: to develop a quality assessment protocol for dialysis service Onofre Lopes University Hospital. It is an intervention project effected through an action research, which consisted of 4 steps. Initially was identified through a literature search in scientific literature, which quality indicators would apply to a dialysis unit being selected as follows: infection rate in hemodialysis access site, microbiological control of water used for hemodialysis and Index User satisfaction. Through critical reflection on the theme researched in the previous step, it was drawn up three data collection instruments, interview form type, applied between the months of October and November 2015. In addition to the information obtained, also made up of the use of information retrieval technique. The results were organized in graphs and tables and analyzed using qualitative and exploratory technical approach. Then a reflective analysis of the data obtained and the diagnosis of reality studied was traced and confronted with the literature was performed. The data produced in this study revealed that the Dialysis Unit of HUOL is much to be desired, considering that some weaknesses have been identified in its structure. Faced with this finding have been proposed, as a contribution and aiming to guide the development of future actions, suggestions for improvement that should be implemented and monitored to be assured overcoming these difficulties, allowing an appropriate organizational restructuring, and resulting in improved service public offered. It was concluded that for hemodialysis treatment results are achieved and positive, it is necessary to have physical structure and adequate infrastructure, multidisciplinary team specialized, trained and in sufficient quantity, well designed processes for professionals to have standards to be followed decreasing the chance to err, and a risk management system to detect and control situations that endanger patient safety.

Evolution of an Interactive Online Magazine for Students, Academics and Expert Practitioners to Engage Students in ESD

Urgency to embed awareness of sustainability principles and practice across society, and need for digital literacy and advocacy for sustainability are reshaping ESD. These, together with developments in learning and teaching, demand new tools to support implementation of project-based learning and more interactive approaches. This investigation explores the evolution of susthingsout.com, an online magazine for students, academics and expert practitioners, developed by the University of Worcester. This comprises two parts; the first, a private site specifically for students involved in sustainability learning on-campus; the second, an open-access site developed to deliver sustainability information and good practice across campus, community and not-for-profit and commercial organisations. This paper involves only the private site i.e. the equivalent of an in-house VLE specifically designed to support the teaching of sustainability to multi-disciplinary first and second year undergraduate students. It reports on the progress of the VLE, following three years of use and initial improvements, in terms of the student support and engagement, as well as considering the practical issues affecting these. The results fall into four categories of pedagogical, operational, cultural and external factors, which are synthesised to capture and share emerging knowledge of good practice offering insights to other developers of online sustainability materials.

Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: experience of four years in a single centre

Background: Balloon pulmonary angioplasty (BPA) has recently been developed as an alternative and less- invasive treatment strategy for chronic thromboembolic pulmonary hypertension (CTEPH), but therapeutic efficacy and technical safety of the technique have to be established. Aim: effects of BPA on patients with inoperable disease or residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). Methods: From June 2015 to September 2019 we enrolled symptomatic (NYHA ≥ II) inoperable CTEPH patients and patients with residual PH after PEA. At baseline, immediately before the first BPA session and 3-6 months after last BPA session all patients underwent clinical evaluation, six-minute walking distance and right heart catheterization. For comparisons Friedman test (with Bonferroni post-hoc pairwise analysis) was used. Survival curves were done with Kaplan Meier method. Results: Forty-seven patients [male 45%, median age 68 (51-74) years, 40 inoperable and 7 with residual PH after PEA] were treated for a total of 136 sessions (median number of sessions for each patient: 2); during each session we treated 2 (2-3) vessels; BPA significantly improved symptoms (NYHA III-IV from 85 to 42%), exercise capacity (from 425 to 446 m) and hemodynamic profile (reduction of mean pulmonary arterial pressure from 41 to 35 mmHg and of pulmonary vascular resistance from 7.1 to 4.7 WU). Five pulmonary artery dissection and 2 hemoptysis with clinical impairment were documented; 33 patients had lung injury (radiographic opacity with/without hemoptysis and/or hypoxemia), 7 patients had access site complications. Five patients died during follow-up (none within 30 days from the procedure) because of sepsis (1), heart failure (1), cancer (1), arrhythmic storm (1) and sudden death in a patient with severe coronary atherosclerosis (1). Conclusions: BPA is a safe and effective treatment able to improve symptoms and hemodynamic profile in inoperable CTEPH patients and in patients with residual PH after PEA.

Conformation analysis of a surface loop that controls active site access in the GH11 xylanase A from Bacillus subtilis

Xylanases (EC 3.2.1.8 endo-1,4-glycosyl hydrolase) catalyze the hydrolysis of xylan, an abundant hemicellulose of plant cell walls. Access to the catalytic site of GH11 xylanases is regulated by movement of a short beta-hairpin, the so-called thumb region, which can adopt open or closed conformations. A crystallographic study has shown that the D11F/R122D mutant of the GH11 xylanase A from Bacillus subtilis (BsXA) displays a stable "open" conformation, and here we report a molecular dynamics simulation study comparing this mutant with the native enzyme over a range of temperatures. The mutant open conformation was stable at 300 and 328 K, however it showed a transition to the closed state at 338 K. Analysis of dihedral angles identified thumb region residues Y113 and T123 as key hinge points which determine the open-closed transition at 338 K. Although the D11F/R122D mutations result in a reduction in local inter-intramolecular hydrogen bonding, the global energies of the open and closed conformations in the native enzyme are equivalent, suggesting that the two conformations are equally accessible. These results indicate that the thumb region shows a broader degree of energetically permissible conformations which regulate the access to the active site region. The R122D mutation contributes to the stability of the open conformation, but is not essential for thumb dynamics, i.e., the wild type enzyme can also adapt to the open conformation.

A general mechanism for regulation of access to the translocon: Competition for a membrane attachment site on ribosomes

For proteins to enter the secretory pathway, the membrane attachment site (M-site) on ribosomes must bind cotranslationally to the Sec61 complex present in the endoplasmic reticulum membrane. The signal recognition particle (SRP) and its receptor (SR) are required for targeting, and the nascent polypeptide associated complex (NAC) prevents inappropriate targeting of nonsecretory nascent chains. In the absence of NAC, any ribosome, regardless of the polypeptide being synthesized, binds to the endoplasmic reticulum membrane, and even nonsecretory proteins are translocated across the endoplasmic reticulum membrane. By occupying the M-site, NAC prevents all ribosome binding unless a signal peptide and SRP are present. The mechanism by which SRP overcomes the NAC block is unknown. We show that signal peptide-bound SRP occupies the M-site and therefore keeps it free of NAC. To expose the M-site and permit ribosome binding, SR can pull SRP away from the M-site without prior release of SRP from the signal peptide.

Molecular determinants of drug access to the receptor site for antiarrhythmic drugs in the cardiac Na+ channel.

The clinical efficacy of local anesthetic and antiarrhythmic drugs is due to their voltage- and frequency-dependent block of Na+ channels. Quaternary local anesthetic analogs such as QX-314, which are permanently charged and membrane-impermeant, effectively block cardiac Na+ channels when applied from either side of the membrane but block neuronal Na+ channels only from the intracellular side. This difference in extracellular access to QX-314 is retained when rat brain rIIA Na+ channel alpha subunits and rat heart rH1 Na+ channel alpha subunits are expressed transiently in tsA-201 cells. Amino acid residues in transmembrane segment S6 of homologous domain IV (IVS6) of Na+ channel alpha subunits have important effects on block by local anesthetic drugs. Although five amino acid residues in IVS6 differ between brain rIIA and cardiac rH1, exchange of these amino acid residues by site-directed mutagenesis showed that only conversion of Thr-1755 in rH1 to Val as in rIIA was sufficient to reduce the rate and extent of block by extracellular QX-314 and slow the escape of drug from closed channels after use-dependent block. Tetrodotoxin also reduced the rate of block by extracellular QX-314 and slowed escape of bound QX-314 via the extracellular pathway in rH1, indicating that QX-314 must move through the pore to escape. QX-314 binding was inhibited by mutation of Phe-1762 in the local anesthetic receptor site of rH1 to Ala whether the drug was applied extracellularly or intracellularly. Thus, QX-314 binds to a single site in the rH1 Na+ channel alpha subunit that contains Phe-1762, whether it is applied from the extracellular or intracellular side of the membrane. Access to that site from the extracellular side of the pore is determined by the amino acid at position 1755 in the rH1 cardiac Na+ channel.

Access to the environment : a series of reference documents on the design and development of site facilities to make them barrier free to the physically handicapped and disabled /

Prepared under contract (H-2002-R) with the Office of Policy Development and Research, Dept. of Housing and Urban Development, and Architectural and Transportation Barriers Compliance Board.