Case Western Reserve University researchers have developed a portable sensor that can assess the clotting ability of a person’s blood 95 times faster than current methods-using only a single drop of blood.
Even better, the device provides more information about the blood than existing approaches.
Rapid and accurate assessments are essential to ensuring that patients prone to blood clots-as well as those who have difficulty clotting-receive care appropriate to their conditions.
Recently, XaTek, a new Cleveland-based company, licensed the technology for the device-called ClotChip-with a goal of bringing it to market within the next three years. Case Western Reserve’s Technology Transfer Office negotiated the agreement between the university and the company.
‘ClotChip is designed to minimize the time and effort for blood-sample preparation. [It can] be used at the doctor’s office or other points of care for patients on anticoagulation therapy, antiplatelet therapy or who have suffered a traumatic injury causing bleeding,’ said Pedram Mohseni, professor of electrical engineering and computer science at Case Western Reserve, who led the development of ClotChip with Michael Suster, senior research associate in the EECS department.
Existing measures typically require patients to visits laboratories where expert technicians administer tests, an approach that typically is time-consuming and expensive. While a few methods exist to allow on-site testing, to date they have not proved nearly as precise as laboratory-based versions.
In preliminary tests, however, Case Western Reserve’s technology provided results in 15 minutes, as compared to conventional measures that can take a day or longer to yield results. ClotChip also provided more information about the coagulation process, including the effects of a new class of drugs called target-specific oral anticoagulants, or TSOACs.
TSOAC drugs block clots from forming in a different way than warfarin which had dominated the market for decades. Warfarin, however, can interact negatively with several medications and foods and also requires frequent blood tests to monitor the drug’s effects.
To monitor clotting, ClotChip uses an electrical technique called miniaturized dielectric spectroscopy, an approach that Mohseni, Suster and their team began developing six years ago. In essence, the technique applies an external electric field to the drop of blood, then quantitatively measures how the blood affects that field. The measurements reflect the ability of the blood to clot.
Because the device works so quickly, emergency responders could use it on site to determine whether a patient in trauma is on one of the blood thinner medications. Such critical information also could be invaluable to medics in wartime.

Case Western Reserve University http://tinyurl.com/zlo6h5s

To provide a better view of difficult to see tissue, Japanese researchers have miniaturized an imaging probe to fit inside a needle that can be inserted into the eye during eye surgery. The probe was used without complications in three human patients.
First, unlike hand-held instruments, the images via probe are generated during surgery to provide real-time information to surgeons. Second, the miniaturized probe can easily scan more of the eye’s interior than microscope-based instruments.
The new technology ‘demonstrated the precise tissue abnormality objectively during surgery, which means the quality of surgery will become better for the patient,’ said author Hiroko Terasaki, MD, PhD, of Nagoya University Graduate School of Medicine.
Future work will involve improving image resolution and further shrinking of the probe to fit into even smaller needles.

ARVO http://tinyurl.com/z2e7c24

Many people who experience chest pain, but don’t have a heart attack, breathe a big sigh of relief when a stress test comes back negative for blockages in their blood vessels. But a new study by cardiac researchers at the Intermountain Medical Center Heart Institute in Salt Lake City found they may not be off the hook after all.

Researchers studied 658 men and women between the ages of 57 and 77 who passed a stress test for blocked arteries and who were later found to have calcium in their arteries after being screened by imaging technology that measured their total coronary artery calcification.

They found that five percent of patients who passed their stress test and later tested high for calcium in their arteries – 31 of 658 patients – went on to have an adverse cardiac event within one year. Such events included death, heart attack and stroke.

Researchers say there is something more doctors can do to assess a patient’s risk of future heart attack: check the calcium – a sign of plaque build-up – in a patient’s arteries.

‘We now have the ability to better measure coronary artery calcification,’ says Viet Le, MPAS, PA-C, lead author of the Intermountain Medical Center Heart Institute study.

‘People say, I’m good. They gave me a stress test,” said Le. ‘But it doesn’t tell the whole story. The story it tells is that on that day your engine – your heart – passed the test. Some of these people die within a year from a heart attack.’

Cardiac experts have known for years that calcium left by plaque is a good marker of heart disease, but there was not good imaging technology to measure it without exposing the patient to too much radiation, Le said. That changed about five years ago.

PET/CT, an advanced nuclear imaging technology that combines positron emission tomography (PET) and computed tomography (CT) in one machine, allows physicians doing a chemical stress test to also measure coronary artery calcification.

Calcification cannot be reversed, but the plaque that causes it can be reduced or stabilized with proper medication, diet and exercise.

Researchers found that 33 patients in the study, or five percent, had no or mild calcification, and they had no cardiac events. But there was a significant correlation between the amount of calcium and the occurrence of cardiac events in the remainder of the patients.

Twelve of 309 (3.88 percent) patients with moderate calcification had a cardiac event within a year, 10 of 190 (5.26 percent) with severe calcification had a cardiac event within a year, and nine of 126 (7.14 percent) with very severe calcification had a cardiac event within a year. In total, 16.28 percent of calcified patients in the study had a heart event.

The results confirmed for Le the value of assessing calcification in patients suspected of having clogged arteries.

‘Right now, it’s a neglected tool that should better be utilized,’ he said.

Intermountain Healthcare intermountainhealthcare.org/news/2016/11/cardiac-pet-ct-imaging-effective-calcium-blockage-assessing-heart-attack-risk/

Scientists at EPFL and ETHZ have developed a new method for building microrobots that could be used in the body to deliver drugs and perform other medical operations.
For the past few years, scientists around the world have been studying ways to use miniature robots to better treat a variety of diseases. The robots are designed to enter the human body, where they can deliver drugs at specific locations or perform precise operations like clearing clogged-up arteries. By replacing invasive, often complicated surgery, they could optimize medicine.
EPFL scientist Selman Sakar teamed up with Hen-Wei Huang and Bradley Nelson at ETHZ to develop a simple and versatile method for building such bio-inspired robots and equipping them with advanced features. They also created a platform for testing several robot designs and studying different modes of locomotion. Their work produced complex reconfigurable microrobots that can be manufactured with high throughput. They built an integrated manipulation platform that can remotely control the robots’ mobility with electromagnetic fields, and cause them to shape-shift using heat.
Unlike conventional robots, these microrobots are soft, flexible, and motor-less. They are made of a biocompatible hydrogel and magnetic nanoparticles. These nanoparticles have two functions. They give the microrobots their shape during the manufacturing process, and make them move and swim when an electromagnetic field is applied.
Building one of these microrobots involves several steps. First, the nanoparticles are placed inside layers of a biocompatible hydrogel. Then an electromagnetic field is applied to orientate the nanoparticles at different parts of the robot, followed by a polymerization step to ‘solidify’ the hydrogel. After this, the robot is placed in water where it folds in specific ways depending on the orientation of the nanoparticles inside the gel, to form the final overall 3D architecture of the microrobot.
Once the final shape is achieved, an electromagnetic field is used to make the robot swim. Then, when heated, the robot changes shape and ‘unfolds’. This fabrication approach allowed the researchers to build microrobots that mimic the bacterium that causes African trypanosomiasis, otherwise known as sleeping sickness. This particular bacterium uses a flagellum for propulsion, but hides it away once inside a person’s bloodstream as a survival mechanism.
The researchers tested different microrobot designs to come up with one that imitates this behaviour. The prototype robot presented in this work has a bacterium-like flagellum that enables it to swim. When heated with a laser, the flagellum wraps around the robot’s body and is ‘hidden’.
‘We show that both a bacterium’s body and its flagellum play an important role in its movement,’ said Sakar. ‘Our new production method lets us test an array of shapes and combinations to obtain the best motion capability for a given task. Our research also provides valuable insight into how bacteria move inside the human body and adapt to changes in their microenvironment.’
For now, the microrobots are still in development. ‘There are many factors we have to take into account,’ says Sakar. ‘For instance, we have to make sure that the microrobots won’t cause any side-effects in patients.’

EPFL http://tinyurl.com/zg3rssf

Researchers working in four labs at UT Southwestern Medical Center have found a chink in a so-called ‘un-druggable’ lung cancer’s armour – and located an existing drug that might provide a treatment.

The study describes how the drug Selinexor (KPT-330) killed lung cancer cells and shrank tumours in mice when used against cancers driven by the aggressive and difficult-to-treat KRAS cancer gene. Selinexor is already in clinical trials for treatment of other types of cancer, primarily leukaemia and lymphoma but also gynaecological, brain, prostate, and head and neck cancers.

Lung cancer is the No. 1 cancer killer in the U.S., responsible for more than 158,000 deaths a year, according to the National Cancer Institute (NCI), and the KRAS oncogene is believed to be responsible for about 25 percent of all lung cancer cases. The 5-year survival rate for lung cancer is below 18 percent.

Cancers caused by the KRAS mutation have been a target for researchers since the mutation was discovered in humans in 1982. But, due in part to this oncogene’s almost impervious spherical shape, no one was able to find an opening for attack, said Dr. Pier Scaglioni, Associate Professor of Internal Medicine at UT Southwestern and a contributing author to the study.

Dr. Michael A. White, Adjunct Professor of Cell Biology and senior author of the study, assembled multiple research teams and used robotic machines to create and sift through trays with thousands of cancer cell/potential drug combinations to uncover the KRAS mutation’s weakness.

The scientists found that targeting and inactivating the protein XPO1, found in the cell nucleus and used to transport gene products from the nucleus to the cytoplasm, killed most of the KRAS mutant cancer cells.

‘We found that inhibiting the XPO1 gene kills lung cancer cells that are dependent on KRAS,’ Dr. Scaglioni said. ‘The unexpected coincidence here is that there is an existing drug that will inhibit XPO1.’

‘We know that this drug hits the XPO1 target in people,’ added Dr. White, also a research executive at Pfizer Inc. ‘But we will not know whether the drug will be effective until clinical trials are done, which should be completed in about two years.’

Based on the results of this study, Selinexor, developed by Karyopharm Therapeutics, will be the focus of a multi-centre lung cancer clinical trial led by UT Southwestern’s Dr. David Gerber, Associate Professor of Internal Medicine. That trial is expected to open for enrolment next year.

UT Southwestern Medical Center www.utsouthwestern.edu/newsroom/news-releases/year-2016/september/kras-cancer-white.html