A new study led by clinician-researchers at Beth Israel Deaconess Medical Center (BIDMC) testing the safety and effectiveness of anticoagulant strategies for patients with atrial fibrillation who undergo stenting procedures has shown that therapies combining the anticoagulant drug rivaroxaban with either single or dual anti-platelet therapy (DAPT) were more effective in preventing bleeding complications than the current standard of care.

Principal Investigator C. Michael Gibson, MD, Chief of Clinical Research in the Division of Cardiovascular Medicine at BIDMC, reported the new research.
The PIONEER AF-PCI randomized clinical trial involved more than 2,100 patients at 430 sites in 26 countries.

Each year, nearly 1 million patients in the United States undergo percutaneous coronary intervention (PCI) and are implanted with stents positioned to treat narrowed coronary arteries. Following PCI, patients receive dual anti-platelet therapy – a combination of aspirin and a second blood-thinning medication – to prevent the formation of blood clots in the stent. Approximately 5 to 8 percent of patients undergoing PCI have atrial fibrillation, the most common type of cardiac arrhythmia and an important risk factor for stroke. These patients typically take a blood thinner, such as warfarin (Coumadin), to prevent stroke.

‘In managing the stented patient with atrial fibrillation, a pharmacologic strategy must carefully balance the risk of stent thrombosis, or blood clot, with the risk of bleeding complications,’ said Gibson, who is also Professor of Medicine at Harvard Medical School and chairman of the PERFUSE (Percutaneous/Pharmacologic Endoluminal Revascularization for Unstable Syndromes Evaluation) Study Group. ‘This trial, which tested two entirely new strategies, now provides us with randomized clinical trial data demonstrating that a combination of rivaroxaban with anti-platelet therapy is successful in minimizing bleeding while preventing clotting.’

Current guidelines call for combining three drugs – DAPT plus a vitamin K antagonist (VKA) anticoagulant – in a strategy known as ‘triple therapy.’ But as the authors note, this approach may result in excess major bleeding rates of 4 to 12 percent within the first year of treatment.

The PIONEER AF-PCI trial studied men and women over age 18 with atrial fibrillation who had undergone a PCI procedure with stent placement. The study subjects were randomly assigned to one of three groups: Group 1 received reduced dose rivaroxaban plus a P2Y-12 inhibitor monotherapy; Group 2 received very low dose rivaroxaban plus DAPT; and Group 3 received VKA plus DAPT.

The findings showed that among patients with atrial fibrillation who underwent intracoronary stent placement, the administration of rivaroxaban in one of two dose strategies reduced the risk of clinically significant bleeding in about one out of every 10 to 11 patients as compared with triple therapy including a vitamin K antagonist. The risks of rehospitalization and death from all causes were also reduced in about one out of every 10 to 15 cases.

‘This new treatment strategy benefits patient health as well as hospital finances,’ added Gibson.

Beth Israel Deaconess Medical Center www.bidmc.org/News/PRLandingPage/2016/November/Gibson-NEJM-AHA.aspx

Researchers from VIB, UGent, the Geisel School of Medicine at Dartmouth and several collaborators developed a new antiviral strategy to fight human respiratory syncytial virus (RSV), a leading cause of lower respiratory tract infections in children. The approach hinges on the use of single-domain antibodies, also known as Nanobodies, which target and neutralize a vital protein in the virus, rendering it unable to enter lung cells. The research elucidates how these Nanobodies interact with and neutralize the virus and demonstrates their ability to successfully protect mice from RSV infection and related inflammation.

RSV annually causes nearly 34 million illnesses in children under 5 years of age and can result in serious illness in both very young children and elderly people leading to hospitalization in up to 2percent of cases. Despite intensive research and the virus’ status as a major pathogen, current methods of treatment rely almost exclusively on supportive care. With the goal of developing a new therapy to fight this disease, Prof. Xavier Saelens (VIB-UGent) and his team developed Nanobodies that target the protein that the virus needs to enter lung cells. The researchers showed that these Nanobodies neutralized the virus in laboratory assays as well as in animals.

To obtain highly potent anti-viral molecules, the group of prof. Saelens collaborated closely with Prof. Jason McLellan’s team from the Geisel School of Medicine and Dr. Barney Graham’s team from the National Institutes of Health in the USA to select, produce and purify Nanobodies that specifically target the active but highly unstable form of the RSV fusion protein. Detailed structural analysis revealed that these Nanobodies tightly bind to a very conserved pocket of the viral fusion protein, and that they provide anti-viral activity against many types of RSV.

Prof. Xavier Saelens (VIB-UGent): ‘We successfully developed molecules that act very potently against RSV, not only against multiple clinical isolates in cell culture, but also in animals. Our Nanobodies are some of – if not the – most potent molecules ever isolated to fight RSV.’

VIB www.vib.be/en/news/Pages/Scientists-isolate-new-antibodies-to-fight-human-respiratory-syncytial-virus-(RSV).aspx

MGH researchers are testing a system for identifying bacterial infections that could save lives, speed recovery and reduce healthcare costs.
Ralph Weissleder, MD, PhD, director of the Massachusetts General Hospital Center for Systems Biology, and Hakho Lee, PhD, also a principal investigator at the centre, are leading a team of researchers that has created such a device. Called Polarization Anisotropy Diagnostics (PAD), it has shown promising results in a small study.
‘We developed a system that is practical and easy to use,’ Dr. Weissleder says. ‘PAD takes the guesswork out of treating patients for bacterial infections.’
The PAD device is about the size of a Rubik’s Cube. And it can make a diagnosis within two hours of receiving a patient sample. By comparison, getting similar results back from a testing lab, can take anywhere from a couple of days to a few weeks. In the meantime, doctors must make a diagnosis based on the patient’s symptoms.
Dr. Weissleder gives this example: A patient comes to the hospital shivering, short of breath and in extreme pain. Healthcare providers suspect a bacterial infection is causing sepsis, a life-threatening infection. They immediately begin treatment, which includes antibiotics-but they don’t know yet which bacteria are making the patient sick. So they prescribe the antibiotic most likely to help or give several types of antibiotics.
When the lab results return two weeks later, the healthcare providers learn if they suspected the right bug. If they were wrong, they must change the course of antibiotics.
But if PAD identifies the bacteria within two hours, physicians can prescribe the right antibiotics sooner. Patients can recover faster, with fewer side effects.
To use the PAD device, a sample from the patient is placed into a tiny vial along with a special detection probe. The vial is slid into a box that snaps onto the PAD cube.
Inside the box, probes search the patient sample for matching bacterial DNA. When a match is detected, the probes glow, sending a signal that specific genes are present. The system uses those genes to identify the bacteria. That data is sent to a smartphone.
On the smartphone screen, PAD identifies whether a bacterial infection is present. The researchers’ current device can already specifically identify nine common infections and determine whether the one involved is resistant to antibiotics.
‘I think over the next couple of years, there will be a switch to rapid diagnostics like our new device.’
In a small study, the team tested its device against the gold standard of having a lab grow a bacteria culture to identify it. PAD did just as well as a lab culture in testing for the presence of the bacteria E. coli, Klebsiella, Acinetobacter, Pseudomonas and Staphylococcus aureus, and in reporting how much bacteria was present and whether it was antibiotic-resistant.

Massachusetts General Hospital http://tinyurl.com/jdbyuwh

New scanning technology which will give a much clearer picture of lung disease has taken a major step forward thanks to scientists at The University of Nottingham.
The experts at the Sir Peter Mansfield Imaging Centre have developed a process using specially treated krypton gas as an inhalable contrast agent to make the spaces inside the lungs show up on an Magnetic resonance imaging (MRI) scan. It’s hoped the new process will eventually allow doctors to virtually see inside the lungs of patients.
Traditional magnetic resonance imaging uses hydrogen protons in the body as molecular targets to give a picture of tissue but this does not give a detailed picture of the lungs because they are full of air. Recent technological developments have led to a novel imaging methodology called Inhaled Hyperpolarized Gas MRI that uses lasers to hyperpolarize’ a noble (inert) gas which aligns (polarizes) the nuclei of the gas so it shows up on an MRI scan.
The work will make 3D imaging using atomic spies’ like helium, xenon, or krypton possible in a single breath hold by the patient. Nottingham has pioneered hyperpolarized krypton MRI and is currently advancing this technology towards the clinical approval processes.
Hyperpolarized MRI research has been trying to overcome a problem with these noble gases retaining their hyperpolarized state for long enough for the gas to be inhaled, held in the lungs and scanned. Now the Nottingham team has developed a new technique to generate hyperpolarized krypton gas at high purity, a step that will significantly facilitate the use of this new contrast agent for pulmonary MRI.
Chair in Translational Imaging at the Sir Peter Mansfield Imaging Centre, Professor Thomas Meersmann, said: "It is particularly demanding to retain the hyperpolarized state of krypton during preparation of this contrast agent. We have solved a problem by using a process that is usually associated with clean energy related sciences. It’s called catalytic hydrogen combustion. To hyperpolarize the krypton-83 gas we diluted it in molecular hydrogen gas for the laser pumping process. After successful laser treatment the hydrogen gas is mixed with molecular oxygen and literally exploded it away in a safe and controlled fashion through a catalysed combustion reaction.
"Remarkably, the hyperpolarized state of krypton-83 survives’ the combustion event. Water vapour, the sole product of the clean’ hydrogen reaction, is easily removed through condensation, leaving behind the purified laser-polarized krypton-83 gas diluted only by small remaining quantities of harmless water vapour. This development significantly improves the potential usefulness of laser-pumped krypton-83 as MRI contrast agent for clinical applications."
This new technique can also be used to hyperpolarize another useful noble gas, xenon-129, and may lead to a cheaper and easier production of this contrast agent.

The University of Nottingham http://tinyurl.com/gwcp75m

Researchers have found that some of the harmful effects of a commonly used cancer drug can be alleviated by using gene therapy that stimulates blood vessel growth in the heart. Doxorubicin treatment, which is commonly used in a variety of cancers, leads to cardiac atrophy and body wasting. Researchers from the Wihuri Research Institute and the University of Helsinki found that in mouse heart, doxorubicin leads to blood vessel rarefaction, which was prevented by treatment with gene therapy using the VEGF-B growth factor.

As advances in cancer treatment have decreased deaths from cancer, doxorubicin-induced heart problems have become an increasing problem. ‘The new findings give hope that in future the heart could be protected by gene therapy, allowing more thorough cytostatic cancer treatment. Thus, the cancer itself would be treated more effectively and the adverse effects could be avoided’, explains Markus Rasanen, MD, who made the discovery during his thesis studies.

‘Doxorubicin, a cytostatic agent of the anthracycline class, that was used in this study has been a target of intensive research in the scientific world for a long time, and its role has been described in thousands of research articles. This research article is the first one, where blood vessel-directed therapy has a clear protective effect against the doxorubicin toxicity’, says Dr. Riikka Kivela, who supervised the study.

‘Our findings show, that especially the endothelial cells, which form the inner surface of the vessels in the heart, have an essential role in the protection against the cardiotoxicity. More preclinical studies are needed though for the development of VEGF-B gene therapy for cardiac protection in patients’, elaborates Rasanen.

University of Helsinki www.helsinki.fi/en/news/a-common-heart-problem-caused-by-cancer-therapy-avoided-blood-vessel-treatment