The standard of care for treating strokes caused by blood clots involves the therapeutic infusion of tissue plasminogen activator (tPA), which can help to dissolve the clots and restore blood flow. This “thrombolytic” treatment carries the risk of bleeding and swelling in the brain, and it must be administered within three hours after the start of the stroke, which sharply limits its clinical benefits.
Edward Feener, Ph.D., colleagues in the Feener lab demonstrated that tPA boosts the activity of plasma kallikrein
Working with animal models, researchers at Joslin Diabetes Center now have demonstrated the potential of giving a drug in combination with tPA that might improve stroke outcomes and increase the window of opportunity for the therapy.
Drugs that target a protein called plasma kallikrein, as well as an activator protein called factor XII, “may provide the opportunity to make tPA safer by reducing these complications and increasing its efficacy in opening blood vessels,” says Edward Feener, Ph.D.
The Joslin scientists next experimented with mouse models in which blood clots were induced in the brain and then treated with tPA. Animals that were also given a plasma kallikrein inhibitor, and animals that were genetically modified to produce lower amounts of the protein, showed significantly less bleeding, brain swelling and damaged brain areas than control animals without plasma kallikrein blockade.
The researchers traced the biological mechanisms by which tPA activates plasma kallikren, via the Factor XII protein, which promotes coagulation. Plasma kallikrein is known to activate the kallikrein kinin system, a pathway that has been implicated in stroke complications including brain swelling and breakdown of the blood-brain barrier. (Previous studies by other investigators have shown that administration of tPA therapy to stroke patients activates the kallikrein kinin system in their blood.)
The Food & Drug Administration has approved a plasma kallikrein inhibitor for the treatment of hereditary angioedema. Additional inhibitors targeting this pathway are under development by multiple pharmaceutical companies for this genetic disease and other conditions, including diabetic macular edema. These new findings suggest additional potential therapeutic opportunities for plasma kallikrein inhibitors in thrombolytic therapy.

Joslin Institutehttp://tinyurl.com/ya3nyyqv

Embryo quality has long been considered the main determinant of implantation and pregnancy in IVF. Morphology – a visual assessment of an embryo’s shape and development – has since the very first days of IVF been the key to measuring this embryo quality, and only in recent years has this morphological grading been made somewhat more scientific with the introduction of time-lapse imaging. Yet the fact remains that many morphologically "good quality" embryos in IVF – between 30 and 60% in various studies – fail to implant in the uterus and make a pregnancy. What’s going wrong?
There is a strong case that chromosomal abnormalities in the embryo, which are not detectable by morphological assessment, carry some responsibility. Studies over several years have confirmed that the rate of chromosomal anomalies (aneuploidy) in embryos increases with patient age, which may explain a higher rate of implantation failure and miscarriage in older IVF patients. But even with embryo testing for chromosomal anomalies, embryos destined for transfer are still assessed morphological.
"The issue is that morphological grading by humans leads to wide inter- and intra-operator variation," said investigator Professor José Celso Rocha from São Paulo State University, Brazil. A study presented today at the 33rd Annual Meeting of ESHRE in Geneva will suggest that these long-standing difficulties may now be improved by using advances in artificial intelligence. Thus, mathematical variables derived from time-lapse images of embryo development may now be used such that an algorithm can classify images of an embryo’s development automatically – and so remove the human variable from the crucial task of morphological assessment. "To classify images automatically will increase the predictive value of our embryo assessment," said Professor Rocha. "By increasing objectivity and repeatability in embryo assessment, we can improve the accuracy of diagnosing embryo viability. Clinics can use this information as ‘artificial intelligence’ to customise treatment strategies and better predict a patient’s chance of pregnancy."
Behind the claims lies an analysis of images taken from the development of 482 seven-day-old bovine embryos, which were used to "train" the artificial intelligence system. This analysis identified 36 assessment variables, 24 of which formed the input of the artificial network architecture. It was notable that during this initial set-up phase only “serious errors” occurred in only 6% of the assessments. Overall, the artificial intelligence system had a 76% accuracy.
Moreover, says Professor Rocha, artificial intelligence demonstrated an improved inter-operator variation (embryologist accuracy score lower than the artificial intelligence score) and improved consistency and overall accuracy of results.
Professor Rocha notes that this work has now moved on to its early stages of development in human embryos, which is being carried out at the São Paulo State University (Dr Marcelo Nogueira) in collaboration with the Boston Place Clinic in London (Dr Cristina Hickman).
Professor Rocha described the main sources of error in morphological assessment by embryologists as their degree of professional experience, emotional stress, physical fatigue, and laboratory routine. "Those features will cause subjectivity in classification of the embryo," he said.
However, because the artificial intelligence system is a technique which analyses the embryo through mathematical variables, it offers low subjectivity and high repeatability, making embryo classification more consistent. "Nevertheless," said Professor Rocha, "the artificial intelligence system must be based on learning from a human being – that is, the experienced embryologists who set the standards of assessment to train the system."

The European Society of Human Reproduction and Embryology
www.eshre2017.eu/Media/ESHRE-2017-Press-releases/Hickman.aspx

The range of options for medicating emergency patients intranasally has greatly expanded in recent years and can even be preferable for certain patients, including children, according to the results of a paper published online.

‘For patients who are combative or having seizures, intranasal administration of certain medications can be really helpful,’ said lead study author Megan Rech, PharmD, MS, BCPS, BCCP of Loyola University Medical Center in Maywood, Ill. ‘These formulations can be especially useful for children, as they are not as painful and frightening as using intravenous or intramuscular routes. This route can also be an effective option for treating opioid overdoses.’

Common medications that can be administered via an atomizer that sprays the surface of the nasal cavity include midazolam, fentanyl, naloxone, ketamine and dexmedetomidine.

Midazolam, administered intranasally, can tranquilize and sedate children who are undergoing numerous emergency procedures. It can also be used to treat seizures in both adults and children. Fentanyl, a synthetic opioid, can be administered to adults and children intranasally for pain relief. Naloxone administered intranasally can be a first-line therapy in suspected opioid overdoses where there is no intravenous access because it can be simply and rapidly administered by lay persons and out-of-hospital personnel. Ketamine, an analgesic, can be administered intranasally for adults and children who have orthopaedic injuries or who are undergoing nasogastric tube placement. Intranasal dexmedetomidine works well to sedate and relieve pain for surgical and dental procedures in children.

‘Administering medications intranasally in the pre-hospital or emergency setting can be easy, fast and non-invasive,’ said Dr. Rech. ‘It is a welcome option for emergency physicians treating a wide variety of patients, sometimes in difficult situations.’

American College of Emergency Physiciansnewsroom.acep.org/news_releases?item=122826

Breast-conserving surgery (BCS) is the primary treatment for early-stage breast cancer, but more accurate techniques are needed to assess resection margins during surgery to avoid the need for follow-up surgeries. Now, in a first-in-human study, British researchers have provided a possible solution using Cerenkov luminescence imaging (CLI), which combines optical and molecular imaging by detecting light emitted by the PET radiotracer F-18-fluorodeoxyglucose (F-18-FDG). CLI’s high-resolution and small-sized imaging equipment make it a promising technology for assessing tumour margins during breast tumour surgery.

‘Currently, approximately 1 in 5 women who undergo breast-conserving surgery, also known as lumpectomy, require repeat surgery due to inadequate excision of the tumour during the initial surgical procedure,’ explains Arnie D. Purushotham, MD, professor at King’s College London, UK. ‘By accurately assessing tumour resection margins intraoperatively with CLI, surgeons may be able to completely clear the cancer with a single operation, thereby reducing the number of breast cancer patients requiring a second, or even third, surgical procedure. Ultimately this could lead to improved patient care and reduced healthcare costs if confirmed in larger clinical studies.’

This study included 22 patients with invasive breast cancer. F-18-FDG was injected 45-60 minutes before surgery. Immediately after the excision of tumours, specimens were imaged intraoperatively in an investigational CLI imaging system. The first 10 patients were used to optimize the imaging protocol; the remaining 12 were included in the analysis dataset. Ten of the 12 patients had an elevated tumour radiance on CLI, and agreement among raters on margin distance was good. Sentinel lymph nodes, which used technetium-99m to facilitate identification, were successfully detected and biopsied in all patients.

F-18-FDG CLI is, therefore, a promising, low-risk technique for intraoperative assessment of tumour margins in breast-conserving surgery. A randomized controlled trial will evaluate the impact of this technique on re-excision rates.

Purushotham points out, ‘The feasibility of intraoperative CLI as shown in this study, in combination with the wide applicability of F-18-FDG across a range of solid cancers, provides a stepping stone for clinical evaluation of this technology in other solid cancer types that also experience incomplete tumour resection due to close or involved margins.’ He also notes, ‘CLI offers the ability to image clinically approved and widely used PET tracers intraoperatively by using small-sized imaging equipment, thus expanding the field of traditional nuclear medicine.’

EurekAlert www.eurekalert.org/pub_releases/2017-06/sonm-coa060117.php

There is effective protection against hip fracture for the many elderly people whose skeleton is declining in strength, as a side effect of cortisone treatment. If patients receive the osteoporosis medication alendronate, it reduces the risk of hip fracture by 65 percent, as a study reveals.
“The low number of people who receive this protective treatment is often due to a lack of knowledge and procedures in this area within the healthcare system,” says Mattias Lorentzon, a professor of geriatric medicine at Sahlgrenska Academy’s Institute of Medicine, and a senior physician at Sahlgrenska University Hospital.
Hip fractures usually affect older people and often lead to disability, a worse quality of life and premature death. For many aged 80 or over, the combination of extensive surgery, immobility and long hospital stays, with a risk of infection, blood clots and confusion, is simply too much.
Cortisone treatment to counteract inflammation conditions such as rheumatoid or muscular arthritis, meanwhile, doubles the risk of hip fracture. This latest study has revealed, however, that just one in four patients treated with cortisone receive the osteoporosis medication alendronate.
The aforementioned study was made possible by interlinking several registers in Sweden, namely Senior Alert, the patient register, the drug register, the cause of death register and the population register.
From a base group of over 400,000 elderly patients, 1802 were prescribed alendronate after starting treatment with the cortisone preparation prednisolone in tablet form. They had been taking the drug for at least three months, at a dosage of at least five milligrams per day.
The group with matched controls, which also consisted of 1802 people, took prednisolone tablets, but did not receive the protective alendronate treatment.
Of those who took cortisone tablets, but did not receive protective treatment, 4.1 percent had broken their hip after around 15 months (1.3 years). In the group that also received alendronate (the protective substance), the equivalent figure was 1.5 percent. This represented a significant reduction in the risk, i.e. 65 percent less, covering other fractures too.
“If a patient receives the protective treatment, the risk of suffering a new fracture, and in particular the new hip fractures that we are really keen to prevent, reduces dramatically,” says Kristian Axelsson, co-author and doctoral candidate, who also works as a resident physician in the orthopedics department at Skaraborgs Hospital.
“The number of patients receiving the treatment is quite low at present, but we are hoping this study will mean more prednisolone patients will receive the fracture-preventing treatment,” he continues.
Most hip fractures occur in older women. The average age in the study was around 80 years, and seven out of ten of the patients were women. There was no increased risk of side effects linked to the alendronate treatment, and for Mattias Lorentzon, it is clear what the study has achieved.
“This drug costs around SEK 200 per person per year, which is nothing really, thanks to the fact that it’s a generic drug for which no patent is outstanding. It’s unlikely any company will invest large amounts of money on a randomized trial to investigate whether it prevents hip fractures in cortisone patients. It perhaps wouldn’t be too ethical either, because there is already indirect evidence that it should work,” he tells us.
“That’s why we wanted to look at the question at issue as part of a major retrospective observational study. The data we now have really supports the argument that it provides effective protection against hip fracture, one of the most costly complaints within the Swedish healthcare system, and something that many people of this age die from. It really helps if you can avoid it,” he concludes.

University of Gothenburg
www.gu.se/english/about_the_university/news-calendar/News_detail/?languageId=100001&contentId=1492013&disableRedirect=true&returnUrl=http%3A%2F%2Fwww.gu.se%2Fomuniversitetet%2Faktuellt%2Fnyheter%2Fdetalj%2F%2Feffektivt-skydd-mot-hoftfraktur-vid-kortisonbehandling.cid1492013