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HAMILTON, ON (November 27, 2019) - A study led by Hamilton researchers has found a new way to interpret blood test results in patients who are investigated for blood clots in their lungs, a condition known as pulmonary embolism.

This new approach applies to D-dimer blood tests, which are used by physicians to rule out the presence of a blood clot. Researchers found that a higher than usual D-dimer level can be considered a negative result if the physician has assessed the patient as having a low probability of having a pulmonary embolism.

The study team notes the findings are important as they mean a lot fewer patients need a computerized tomography (CT) scan, which results in patients avoiding radiation exposure and spending less time in the emergency department. The health system also benefits, they say, as it frees up CT scans for other patients and it improves ability to move patients more quickly through the emergency department.

The study results were published today in the New England Journal of Medicine.

"The primary goal of diagnostic testing for pulmonary embolism is to identify which patients should be treated with anticoagulant agents and which should not," said first author Clive Kearon, professor of medicine at McMaster University and a thrombosis specialist with Hamilton Health Sciences.

"When a physician is concerned that pulmonary embolism may be present, chest imaging with CT pulmonary angiography is usually done in half of these patients. We wanted to find a way to reduce the number of CT scans that need to be done."

A total of 2,017 patients aged 18 and older were enrolled and evaluated in the study, of which seven per cent had pulmonary embolism on initial diagnostic testing. The average age of the patients was 52 years, and 66 per cent were female.

Of the patients in the study, 73 per cent, or 1,474, were enrolled at Hamilton Health Sciences or St. Joseph's Healthcare Hamilton.

These patients, and those at other university-based clinical centres in Canada, were tested from December 2015 through May 2018 and assessed 90 days later.

Of the 1,325 patients identified by an emergency department physician as having a low (1,285 of the patients) or a moderate (40 patients) probability of having a pulmonary embolism and who had negative D-dimer results (that is, less than 1,000 or 500 nanograms per millilitre (ng/mL) respectively), none had venous thromboembolism during follow-up.

"Our analyses show that pulmonary embolism is ruled out by a D-dimer level of less than 1,000 ng/mL in patients with a low probability, and by a D-dimer level of less than 500 ng/mL in patients with a moderate probability. This way of using D-dimer testing and clinical assessment reduced the need for CT scanning by one-third," said Kearon.

"This was a collaborative study among thrombosis and emergency medicine physicians and researchers. Dr. Kerstin de Wit, who is an emergency medicine and thrombosis specialist, was key to this research and to the study's translation."

Atrial fibrillation, also known as AFib, is the most common type of irregular heartbeat, and it is associated with increased mortality. While researchers have identified a causal link between obesity and AFib, the underlying mechanism of how obesity contributes to the heart arrhythmia is still unknown.

A new study from researchers at the University of Illinois at Chicago is the first to show that some antiarrhythmic medications used to treat AFib are less effective in patients who are obese. The results of this study, which followed more than 300 patients in the UIC AFib Registry, are published in JAMA Cardiology.

According to UIC's Dr. Dawood Darbar, senior author on the study, response to current antiarrhythmic drug treatment for AFib is highly variable and unpredictable, and medication selection depends on the treating physician. There are no guidelines to suggest whether Class I drugs -- which work on sodium channels in the heart to regulate heartbeat -- or Class III drugs --those that target potassium channels -- work best in which patients. Previously, it was assumed that both antiarrhythmic drugs were equally effective in preventing reoccurrences of AFib.

In the new study, Darbar and his colleagues have shown that Class I drug treatment showed increased rates of AFib reoccurrences in obese patients compared with nonobese patients -- approximately 30% of obese patients had AFib reoccurrence, compared with only 6% of nonobese patients. This effect was not seen among patients treated with Class III drugs.

Similar results were replicated in a study of obese and nonobese mice.

"This is the first time anyone has shown that there is a differential response to antiarrhythmic drugs for AFib," said Darbar, professor and head of cardiology at the College of Medicine. "As 50% of the patients in our AFib Registry are obese, this provided us with a unique opportunity to determine whether obesity affected response to drug treatment for AFib. Our study provides new information that physicians can use to guide their decisions for obese patients with AFib.

"This may particularly impact the health of ethnic minorities who are more likely to experience obesity," he said.

More than 50% of the obese patients in the study were part of an ethnic minority group. While the prevalence of AFib is low in ethnic minority populations, their outcomes are graver.

"With the obesity epidemic increasing, it leaves these populations at risk," Darbar said. "Having treatment options to better manage AFib would greatly improve quality of life and could prevent the risk of serious complications, like stroke, which can cause early death."

Darbar and his colleagues ultimately hope to uncover the underlying mechanism of how obesity hinders Class I antiarrhythmic drugs and find new and targeted AFib treatment options.

There are three treatment options commonly used by doctors in the emergency room to treat patients with refractory status epilepticus, severe seizures that continue even after benzodiazepine medications, which are effective in controlling seizures in more than two-thirds of patients. New findings published in the New England Journal of Medicine reveal that the three drugs, levetiracetam, fosphenytoin, and valproate, are equally safe and effective in treating patients with this condition. The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

"Doctors can be confident that the particular treatment they choose for their patients with status epilepticus is safe and effective and may help them avoid the need to intubate the patient as well as stays in the intensive care unit," said Robin Conwit, M.D., NINDS program director and an author of the study. "This was a truly collaborative, multidisciplinary study that involved pediatricians, emergency medicine doctors, neurologists, pharmacologists, and biostatisticians all contributing their expertise."

In the Established Status Epilepticus Treatment Trial (ESETT), led by Robert Silbergleit, M.D., professor at the University of Michigan, Ann Arbor; Jordan Elm, Ph.D., professor at Medical University of South Carolina; James Chamberlain, M.D., professor at George Washington University; and Jaideep Kapur, M.B., B.S., Ph.D., professor at the University of Virginia, more than 380 children and adults were randomized to receive levetiracetam, fosphenytoin, or valproate when they came to the emergency room experiencing a seizure. The researchers were trying to determine which of the anticonvulsant drugs was most effective in stopping seizures and improving a patient's level of responsiveness within 60 minutes of administering treatment.

The results showed that the three drugs stopped seizures and improved responsiveness in approximately half of the study participants. Specifically, these benefits were seen in 47% of subjects in the levetiracetam group, in 45% of participants in the fosphenytoin group and in 46% of subjects in the valproate group. These differences were not statistically significant.

There were no differences in serious side effects among the drugs.

"Our study suggests that clinical outcomes are driven by factors other than drugs. Differences in how doctors decide to treat status epilepticus, such as when they give more drugs or when to anesthetize patients and put them on a mechanical ventilator, may be more important than the specific treatments used to control seizures in patients," said Dr. Silbergleit.

The study was stopped early when a planned interim analysis found that the drugs were equally safe and effective.

ESETT researchers utilized a clinical trial design known as response adaptive randomization to improve the study's efficiency and maximize the chances of identifying the best treatment. The study used an algorithm to determine which drugs patients would receive based on accumulating trial data.

"Using an innovative design for this clinical trial, we were able to answer this important question in a timely and cost-effective manner," said Dr. Kapur. "In addition, this design lowered risk by reducing the chances that participants could have received what might have been determined to be the least effective treatment."

Status epilepticus is characterized by individual seizures or multiple seizures close together lasting more than five minutes, with a loss of consciousness. If not treated, it can lead to severe brain damage or death. Benzodiazepines are the first line of treatment for status epilepticus and are effective in two-thirds of patients. Refractory status epilepticus occurs in those patients in whom benzodiazepines do not stop their seizures.

Additional research is needed to prevent refractory status epilepticus and to find treatment options for the patients whose seizures do not respond to the three drugs investigated in this study.

Early use of breast milk could play a vital role in preventing heart disease in prematurely born infants, according to a paper led by researchers at RCSI (Royal College of Surgeons in Ireland) and the Rotunda Hospital.

The review article, published in the journal Pediatric Research, was written in collaboration with researchers from Harvard Medical School, University of Oxford and University of Toronto.

One of the long-term health complications that young adults born prematurely may have is unique heart characteristics. These can include smaller heart chambers, relatively higher blood pressure, and a disproportionate increase in muscle mass in the heart.

One study cited in the article looked at 30 preterm-born adults who were assigned to receive exclusive human milk and 16 preterm-born adults who were assigned to receive an exclusive formula-based diet during their hospital stay at birth. They then underwent detailed cardiovascular assessment between 23 and 28 years of age, including an MRI of their hearts. As expected, all of the hearts of those born prematurely had smaller chambers than the hearts in people who were not born prematurely.

However, the study showed that the smaller heart chambers were less profound for the exclusively human milk-fed group in comparison to those who were exclusively formula fed, suggesting a potentially protective effect of human milk for heart structure.

The researchers then identified potential reasons for why breast milk results in a lower risk of heart disease. Breast milk could help prevent heart disease by better regulating hormones and growth factors, strengthening the infant's immune system, reducing inflammation and by possibly improving the metabolism of the child.

Identifying the key components within breast milk that result in improved heart health could pave the way for a more targeted approach to improve long-term cardiovascular wellbeing for those born prematurely.

"It is becoming increasingly clear that premature birth results in long-term adverse cardiovascular effects with important clinical consequences. There is a distinct lack of preventative and therapeutic interventions available to alleviate those effects," said Professor Afif EL-Khuffash, Honorary Clinical Professor of Paediatrics at RCSI and Consultant Neonatologist at The Rotunda Hospital, Dublin.

"The current evidence comes from observational studies and highlights the strong link between early breast milk administrations and improvement in long-term heart health, but it lacks concrete mechanistic explanations. More studies on the composition of breast milk could make clear exactly what causes these health benefits, which could in turn lead to better treatment options."

The collaborative research group is continuing to study the effects of human milk exposure on heart function in very premature infants by using novel scans to measure heart function. They hope to demonstrate that early human milk exposure in premature infants can lead to significant improvements in heart function over the first two years of age.

A group of researchers from the University of Seville and the Seville Biomedicine Institute (Instituto de Biomedicina de Sevilla - IBiS) has published a study in which they determine that a protein called CD44 makes it possible to identify the population of mother cells that are responsible for the aggressive nature and low survival rate of neuroblastoma, a type of childhood cancer that mainly affects children of two and three years old.

"We believe that the protein CD44 contributes to the aggressive behaviour of the cancerous mother cells responsible for tumour growth and for metastasis. We believe that interrupting the functioning of this cell adhesion molecule can offer a new therapeutic option to eliminate these cells and so improve the treatment of neuroblastoma", explains the researcher and author of the study, Ricardo Pardal.

Tumour samples were used in the research taken from patients with neuroblastoma at the University Hospital Virgen del Rocio in Seville, following all the ethical and legal requirements that are obligatory in this type of research. The study took place in the laboratories of Centre for Research, Technology and Innovation at the University of Seville (Centro de Investigación, Tecnología e Innovación de la Universidad de Sevilla - CITIUS) and the Seville Biomedicine Institute (IBiS).

"Our results would not be able to improve prevention but they would improve diagnosis of the disease, affecting our ability to refine the type of treatment needed in a subgroup of patients suffering with neuroblastoma. Therefore, these findings should help to optimise the prognosis and treatment of neuroblastoma, at least in a subgroup of patients which presents high levels of CD44 in their tumours", Doctor Pardal adds.

This research was codirected by the University of Seville teachers Ricardo Pardal and Francisco M. Vega, de la Universidad de Sevilla, and was funded by Spanish Cancer Association (Asociación Española contra el Cáncer - AECC), the SAF programme of the Spanish Ministry of Science and Innovation and the European Research Council (ERC Starting Grant). In addition, the work counted on the collaboration of Asociación de Pacientes NEN (Niños Enfermos de Neuroblastoma - an association for children suffering with neuroblastoma), whose efforts helped, in an important way, with continued advances in the treatment of this drastic disease.

MALT1 blockers have long been in clinical use for the treatment of blood cancers. A study suggests that these drugs could potentially also be developed as a treatment option for glioblastoma, the most common and lethal type of brain tumour.

Heidelberg, 27 November 2019 - For a long time, cancer research has largely focused on so-called oncogenes - genes that can cause cancer when mutated. While targeting these genes has led to the successful development of a number of valuable drugs, this approach is hampered by the fact that tumours often become resistant to these treatments.

A study conducted by Julie Gavard at the Université de Nantes, CNRS, INSERM, France, and her team, published today in The EMBO Journal, is now based on a different concept, termed non-oncogene addiction. During disease progression, cancer cells become strongly dependent on normal genes and cell functions to survive. These genes could thus serve as potential targets to attack tumour growth more efficiently. A gene called mucosa-associated lymphoid tissue l (MALT1), for example, is highly active in lymphoma, a type of blood cancer, and blocking MALT1 causes lymphoma cells to die. MALT1 blockers have been viewed as a promising new treatment for lymphomas.

The researchers now addressed the role of MALT1 in solid tumours, namely glioblastoma. Using data from The Cancer Genome Atlas, a molecular characterization of over 20,000 primary cancers, they revealed that MALT1 levels strongly correlate with patients' survival in brain cancer - patients with less MALT1 tend to live longer.

Gavard and colleagues then focused their attention on so-called glioblastoma stem cells, a self-renewing subpopulation of cells within the tumour that are likely responsible for cancer recurrence after treatment. They uncovered that targeting MALT1 with MALT1 blockers caused glioblastoma stem cells to undergo a rare form of cellular suicide termed lysosomal cell death in human cell culture experiments. Lysosomes are organelles within the cell that serve as the cells' digestive system. MALT1 keeps lysosomes low in cancer cells, which is crucial for their survival. Blocking MALT1 leads to an increase in lysosomes, which in turn impairs the cells' waste disposal system, eventually killing them. This points to the possibility of further exploring MALT1 inhibitors as potential treatment of glioblastoma.

Scientists at the University of Surrey have developed a novel vaccine and complementary skin test to protect cattle against bovine tuberculosis (bovine TB).

Publishing their findings in the journal Scientific Reports, researchers reveal they have for the first time created a vaccine that is compatible with a synthetic form of the tuberculin skin test (PPD), a legally required test used for the surveillance of TB in cattle throughout the UK.

Bovine TB is an infectious disease in cattle affecting their lungs, and those that test positive for the disease are culled. The BCG vaccine, which is currently used to protect humans against TB and is effective in cattle, is incompatible with the PPD test. Cattle that are vaccinated with the BCG vaccine, which contains a harmless strain of the bovine TB pathogen Mycobacterium bovis, produce a positive PPD test for TB making it impossible to distinguish, with the PPD skin test, if the animal has TB or has simply been vaccinated.

Vaccinating cows with BCG is therefore banned in most countries in the world, enabling vets to continue to use the PPD skin test to diagnose the disease in cattle.

During this innovative study, researchers sought to make a new BCG vaccine strain that lacks some of the proteins that are shared with the pathogen Mycobacterium bovis by identifying genes that contain encoded immunogenic proteins that could be removed from BCG without affecting its ability to work as a live vaccine. To do this, a collection of BCG strains that had each lost a single gene were injected into cows and survival rates measured. This allowed the team to identify genes that could be removed without compromising the BCG vaccine's effectiveness.

These dispensable genes encoding immunogenic proteins were then deleted from the BCG chromosome to make a BCG-minus strain. The deleted immunogenic proteins were then used to develop a new synthetic skin test that, like PPD, will be positive for animals that have been exposed to TB but, unlike PPD, will be negative for animals that have been vaccinated with the BCG-minus strain.

The protective efficiency of the new strain was tested in guinea pigs. It was found that TB-infected guinea pigs tested positive for the disease using the synthetic skin test whilst guinea pigs vaccinated with the BCG-minus strain did not. So, unlike PPD, the new skin test also works in animals that are protected from TB by BCG-minus vaccination. This potentially allows farmers and veterinarians to protect their animals with the new BCG vaccine, whilst still maintaining a diagnostic test that will detect TB.

Johnjoe McFadden, Professor of Molecular Genetics at the University of Surrey, said: "In order to control the spread of bovine TB, effective vaccination and accurate early diagnosis of the disease are critical. This new vaccine provides protection against bovine TB and will help in the fight against this deadly disease which infects over 50 million cattle worldwide and is economically devastating to farmers.

"The next stage of our work will be to demonstrate that both synthetic skin test and BCG-minus vaccine works in cattle herds. If they do, then it will be possible to vaccinate cattle against TB yet retain the value of skin test for diagnosis.

ANN ARBOR, Mich. - A new study finds that the three most common treatment options administered in the emergency department for patients who experience refractory status epilepticus are equally safe and effective.

Status epilepticus is characterized by individual seizures or multiple seizures close together lasting more than five minutes with a loss of consciousness. If not treated, it can lead to severe brain damage or death.

Benzodiazepines, a class of sedating medications that target the central nervous system, are the first line of treatment for status epilepticus and are effective in two-thirds of patients. Refractory status epilepticus occurs in those patients in whom benzodiazepines don't stop their seizures.

"Optimizing emergency treatment with benzodiazepines has previously proven to reduce intensive care unit stays, hospitalization and other complications, but we have not had clinical trial data to tell us what works in those patients who continue to seize despite benzodiazepines," says Robert Silbergleit, M.D., a professor of emergency medicine at Michigan Medicine.

"Although levetiracetam, fosphenytoin and valproate are three of the most commonly used intravenous drugs to treat refractory status epilepticus in both children and adults, before this study, we didn't know if one of these drugs worked better, or if any of them worked well at all."

Silbergleit is the senior author of the new study, published in the New England Journal of Medicine, which reveals the three drugs are equally safe and effective in treating patients with refractory status epilepticus. The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

"Doctors can be confident that the particular treatment they choose for their patients with status epilepticus is safe and effective and may help them avoid the need to intubate the patient as well as stays in the intensive care unit," says Robin Conwit, M.D., NINDS program director and an author of the study.

"This was a truly collaborative, multidisciplinary study that involved pediatricians, emergency medicine doctors, neurologists, pharmacologists and biostatisticians all contributing their expertise."

Trial results

In the Established Status Epilepticus Treatment Trial (ESETT), more than 380 children and adults were randomized to receive levetiracetam, fosphenytoin or valproate when they came to the emergency department experiencing prolonged seizures.

Silbergleit, along with lead co-authors Jordan Elm, Ph.D., a professor at Medical University of South Carolina, James Chamberlain, M.D., a professor at George Washington University and Jaideep Kapur, M.B., B.S., Ph.D., a professor at the University of Virginia, hoped to determine which of the anticonvulsant drugs was most effective in stopping seizures and improving a patient's level of responsiveness within 60 minutes of administering treatment.

The results showed that the three drugs stopped seizures and improved responsiveness in approximately half of the study participants. Specifically, these benefits were seen in 47% of subjects in the levetiracetam group, in 45% of participants in the fosphenytoin group and in 46% of subjects in the valproate group. These differences weren't statistically significant and there were no differences in serious side effects among the drugs.

"Our study suggests that clinical outcomes are driven by factors other than drugs," Silbergleit says.

"Differences in how doctors decide to treat status epilepticus, such as when they give more drugs or when to anesthetize patients and put them on a mechanical ventilator, may be more important than the specific treatments used to control seizures in patients."

The study was stopped early when a planned interim analysis found that the drugs were equally safe and effective.

The ESETT researchers utilized a clinical trial design known as response adaptive randomization to improve the study's efficiency and maximize the chances of identifying the best treatment. The study used an algorithm to determine which drugs patients would receive based on accumulating trial data.

"Using an innovative design for this clinical trial, we were able to answer this important question in a timely and cost-effective manner," Kapur says. "In addition, this design lowered risk by reducing the chances that participants could have received what might have been determined to be the least effective treatment."

Future use

Silbergleit notes that the results of ESETT validate the use of the three drugs and give emergency physicians options when it comes to treating patients with refractory status epilepticus.

"Of the three medications tested, only fosphenytoin is labeled by the Food and Drug Administration as a treatment for status epilepticus, and it is only approved for status epilepticus in adult patients," he says.

"Our results demonstrate that doctors can choose a treatment based on availability, as shortages of these drugs have been common in recent years, cost, ease of administration or other practical criteria."

Additional research is needed to prevent refractory status epilepticus and to find treatment options for the patients whose seizures don't respond to the three drugs investigated in this study.

New study suggests that less than a fifth of shoppers were aware of the need for tests of the pressure inside their eyes (intraocular pressure), when measured at a Pop-Up health check station set up across eight shopping centres in England.

High intraocular pressure is a major risk factor for 'primary open angle glaucoma' (POAG), the most common form of glaucoma1, as well as other forms.

The researchers from City, University of London invited passers-by to the one-day Pop-Up health check stations to answer questions about their eye health, including whether they knew anything about their 'eye pressure', and to have a simple test to check their intraocular pressure with a hand-held 'tonometer'. In total, 858 volunteers agreed to answer questions about their eye pressure, and 768 of those agreed to be tested.

In half of cases, volunteers were also invited to have their blood pressure tested to see whether this widely known, general health check might increase pick-up of the test of intraocular pressure, and thus raise awareness of having it checked and the importance of visiting an optometrist regularly. Combined testing was held on a different day to the test of intraocular pressure alone.

The study found that only 19% of shoppers knew anything about their intraocular pressure, including the tonometer test for it; as opposed to 71% who had some knowledge about their blood pressure.

The study also found that when the intraocular test was advertised alongside the blood pressure test, significantly more shoppers took up the opportunity to answer questions and get tested for both. When advertised together 60% of those asked agreed to participate, as opposed to only 40% when the intraocular test was advertised alone.

Glaucoma is an umbrella term for a group of degenerative diseases of the optic nerve at the back of the eye, which can cause irreversible loss of a person's field of vision, and is estimated to represent 11% of cases of serious sight impairment in the UK, second only to macular degeneration2.

In England, 90% of referrals for cases of suspected glaucoma into secondary specialist care are the result of opportunistic case findings by optometrists3-5, but it is estimated that one third of primary open angle glaucoma cases remain undiagnosed in the UK6.

The Pop-Up Health Check stations were set up in shopping centres in Bristol, Cambridge, Coventry, Northampton, Nottingham, Preston and Stoke-on-Trent.

Dr Laura Edwards is a Postdoctoral Research Fellow at Moorfield's Eye Hospital and led on the study testing while at the Crabb Lab at City, University of London. She said:

"Awareness of eye pressure among the public is abysmally low. Whilst a definitive diagnosis of glaucoma requires many tests, we wanted to see whether advertising and administering one of the tests directly to the public in a targeted community setting was feasible and could raise awareness of the importance of this aspect of eye health.

"More people engaged with our Pop-Up stations on days when our eye health check was offered alongside testing blood pressure, which suggests that an unfamiliar health message can be promoted by aligning it with one that the public is more familiar with.

"We hope our findings can inform strategies for public health schemes that engage the public with their eye health and promote education about the importance of regular eye examinations."

The research is published, open access, in the journal, BMJ Open.

BELLINGHAM, Washington, USA, and CARDIFF, UK - In an article published in the peer-reviewed SPIE publication Journal of Biomedical Optics (JBO), "Influence of neoadjuvant chemotherapy on diffuse reflectance spectra of tissue in breast surgery specimens," research observed across 92 ex vivo breast specimens suggests that there is little to no impact on the optical signatures of breast tissue after neoadjuvant chemotherapy.

The results of the study, in which diffuse reflectance spectroscopy (DRS) measurements were performed on 92 ex vivo breast specimens from 92 patients treated with and without neoadjuvant chemotherapy, show that contrast between healthy tissue and tumor tissue is not altered due to neoadjuvant chemotherapy, suggesting that the same reflectance spectral signatures can be used for tumor margin guidance independent of the chemotherapy status of the patient.

Because healthy and tumor tissue can be readily discriminated, tumor-margin assessment by DRS -- which can discriminate different tissue types based on optical characteristics -- becomes a feasible consideration during breast-conserving surgery, even if the patient has received neoadjuvant chemotherapy prior to surgery, a procedure that has become commonplace. The ultimate goal of the intra-surgery application of DRS would allow the surgeon to assess the tissue while performing the resection of tumors to ensure that the resection margin is clear of tumor tissue.

According to JBO Editor-in-Chief, SPIE Fellow, and MacLean Professor of Engineering at the Thayer School of Engineering at Dartmouth College, New Hampshire, Brian W. Pogue, the paper and its findings are notable due to the large number of clinical samples analyzed, and the consequent relevance to assessing neoadjuvant chemotherapy changes. "While a significant amount of work has been done defining the spectral signatures of breast cancer tumors and showing that this can be used for guidance, this is one of the first attempts to examine tumors following neoadjuvant chemotherapy as well. The results show that the signatures do not appear to change and so the status of the patient would not confound spectral imaging to help define the lumpectomy margin."

Scientists have found a type of transmissible cancer in shellfish that has spread across the Atlantic Ocean and even into the Pacific. The new study was published in eLife.

The CUIMC Newsroom interviewed Stephen Goff, PhD, an expert in transmissible cancers at Columbia University and a co-author of the paper, to learn more about how cancer can spread in shellfish colonies separated by thousands of miles of water, and how that could help us better understand cancer metastasis in other organisms.

Wait, cancer can be contagious?

Yes, but it's a rare occurrence. So far scientists have only observed contagious cancers in three types of animals: Tasmanian devils, dogs, and shellfish. None of these cancers can be transmitted to humans. There are viruses like human papillomavirus (HPV) that cause cancer, but in these cases, it's the virus that spreads, not the cancer cells.

How is cancer transmitted in these animals?

It's known that Tasmanian devils and dogs can transmit cancer cells to other members of their species via bites and sex, respectively.

Columbia researchers in the lab of Stephen P. Goff, PhD, at Columbia University Vagelos College of Physicians and Surgeons, were the first to discover contagious cancers in marine animals. In four separate species of clams, they found that cancer cells could travel through ocean water from one clam to another to spread the disease. Surprisingly, the researchers found that some contagious cancer cells could "infect" a different species of clam.

How widespread is this phenomenon?

In the new study, the researchers collaborated with marine biologists in South America and Europe. They found similar cases of contagious cancers in different mussel species along the coasts of Argentina, Chile, France, and the Netherlands. In some mussel colonies, the cancer was so contagious that it had infected 13% of the population.

The most surprising finding came when the researchers compared French and Chilean mussels. Both populations contained cancer cells that were genetically identical, despite being separated by vast distances. Even Chilean mussels in the Pacific Ocean and French mussels in the Atlantic had identical cancer cells. In other words, the cancer cells had somehow travelled more than 7,000 miles across hemispheres and oceans to infect other organisms. The cancer clone had even spread into species of mussels that were different from the species in which the cancer first arose.

The scientists suspect that the cancer cells had some help. Currents present a significant barrier to the travel of individual cells through the ocean. But mussels are known to attach themselves to the hulls of ships. It is likely that ships transported infected mussels from continent to continent, delivering the disease to new regions.

Ok, but that sounds a little terrifying and now I'm worried about eating seafood

It's absolutely ok to eat seafood. The cancers are specific to shellfish and do not appear to pose a danger to humans who eat them. In humans, cancers originate within a person's body and, as far as we know, can't spread to other people, except in rare cases, such as through organ transplants or during pregnancy.

The researchers think that shellfish are more prone to transmissible cancer because they live in the ocean where malignant cells can easily travel. These animals eat by pumping and filtering huge quantities of water, and they have a very limited immune system that may not be able to block transmission.

So, how will this work help?

Research on how contagious cancers spread in shellfish will help biologists develop more effective plans to protect marine life. And though transmissible cancers in shellfish don't pose a threat to humans, studies of these cancers could be valuable to medical researchers.

"There are parallels between how cancers spread in the ocean and how cancer cells metastasize within humans," says Goff. "Learning more about contagious cancers in shellfish could help us find ways to prevent the metastatic spread of tumors to new sites in the body."

Results from the NRG Oncology phase I clinical trial NRG-GOG 9929 show that utilizing the immunotherapy drug ipilimumab after chemoradiotherapy (CRT) is tolerated in the curative treatment of women with lymph node-positive cervical cancer. The maximum tolerated dose of ipilimumab was determined to be 10 mg/kg. These results are published in JAMA Oncology and was be highlighted at a gynecologic session during the American Society for Radiation Oncology's (ASTRO) Annual Meeting in September 2019.

NRG-GOG 9929 is the first trial to describe the safety of immunotherapy following CRT in curative cervical cancer. Currently, many women with node-positive cervical cancer who are treated with CRT will recur. Therein lies the need to develop a safe and effective therapeutic strategy, such as the use of immunotherapy, to improve outcomes for women with this type of cancer. NRG-GOG 9929 was designed to primarily determine the safety and proper dosage of ipilimumab (immunotherapy) following the standard CRT treatment; however, a secondary endpoint included in the trial was measuring survival outcomes.

Twenty-one patients on NRG-GOG 9929 received CRT followed by ipilimumab (immunotherapy). Patients received one of two potential dose levels, 3mg/kg (DL1) and 10mg/kg (DL2), in order to determine the maximum dose of immunotherapy. Only 2 patients experienced self-limited grade 3 toxicities. The 12-month progression free survival rate was 81% and the 12-month overall survival rate was 90%. All patients completed CRT, 86% of women completed 4 cycles of ipilimumab, and 14% of women completed 2 cycles of ipilimumab. PD-1 expression increased with CRT and was sustained with immunotherapy.

"Future researchers should consider the findings of this prospective phase 1 trial when developing clinical trials for women with node-positive cervical cancer. We need to have more studies and investigations that will help to identify therapeutic targets to improve outcomes in this patient population," stated Jyoti S. Mayadev, MD, of University of California San Diego School of Medicine and lead author of NRG-GOG 9929.

Researchers at Karolinska Institutet have developed a new method to separate between two different types of a common herpes virus (HHV-6) that has been linked to multiple sclerosis. By analyzing antibodies in the blood against the most divergent proteins of herpesvirus 6A and 6B, the researchers were able to show that MS-patients carry the herpesvirus 6A to a greater extent than healthy individuals. The findings, published in Frontiers in Immunology, point to a role for HHV-6A in the development of MS.

Multiple sclerosis, MS, is an autoimmune disease that affects the central nervous system. The cause of the disease is unclear, but one plausible explanation is a virus tricks the immune system to attack the body's own tissue. Human Herpesvirus 6 (HHV-6) has previously been associated with MS, but in those studies it wasn't possible to distinguish between 6A and 6B. Through virus isolation from ill individuals, researchers have been able to show that HHV-6B can cause mild conditions such as roseola in children, but it has been unclear if HHV-6A is the cause of any disease.

According to estimates, as many as 80 percent of all children are infected with the HHV-6 virus before 2 years of age, and many also carry protection in the form of antibodies against this particular virus for the rest of their lives. But since it hasn't been possible to tell the two variants apart post-infection, it has been difficult to say whether HHV-6A or B is a risk factor for MS.

In this study, however, the researchers were able to distinguish between the A and B virus by analyzing antibodies in the blood against the proteins--immediate early protein 1A and 1B (IE1A and IE1B)--that diverge the most between the two viruses.

"This is a big breakthrough for both the MS and herpes virus research," says Anna Fogdell-Hahn, associate professor at the Department of Clinical Neuroscience at Karolinska Institutet and one of the study's senior authors. "For one, it supports the theory that HHV-6A could be a contributing factor to the development of MS. On top of that, we are now able, with this new method, to find out how common these two different types of HHV-6 are, something we haven't been able to do previously."

The researchers compared antibody levels in blood samples of some 8,700 MS-patients against more than 7,200 healthy people whose gender, date of birth, date of blood sample and other factors matched those with MS. They concluded that people with MS had a 55 percent higher risk of carrying antibodies against the HHV-6A protein than the control group. In a sub-group of almost 500 people, whose blood samples were drawn before the onset of the disease, the risk of developing MS in the future was more than doubled if they had a 6A viral infection. The younger the people were when the virus was first discovered in the blood, the higher the risk was of developing MS in the future. HHV-6B, on the other hand, was not positively associated with MS. Instead MS-patients had lower levels of antibodies toward IE1B than those without MS.

Antibodies toward Epstein-Barr virus (EBV), another herpes virus that is also associated with MS, were analyzed with the same method and the researchers were able to show that individuals affected with both viruses had an even greater risk of MS. This indicates that several virus infections could be acting jointly to increase the risk of MS.

"Both HHV-6A and 6B can infect our braincells, but they do it in slightly different ways. Therefore, it is now interesting to go forward and attempt to map out exactly how the viruses could affect the onset of MS," says Anna Fogdell-Hahn.

Children of women who reported domestic violence in pregnancy or during the first six years of the child's life are almost 50% more likely to have a low IQ at age 8, research finds.

In the study by University of Manchester epidemiologists, 13% of children whose mothers did not experience domestic violence had an IQ of below 90 at 8 years of age.

If their mothers experienced physical violence from their partner either in pregnancy or during the first six years of the child's life, the figure rises to 22.8%.

The team led by Dr Kathryn Abel from The University of Manchester show the chance of a low IQ rises to 34.6% if the mother was repeatedly exposed to domestic violence.

That means children with mothers who repeatedly suffer domestic violence during pregnancy and the first six years of their child's life are almost three times more likely to have a low IQ at 8 years of age, find researchers.

Low IQ is defined as an IQ score less than 90, where a normal IQ is considered to be 100.

The study examined the link between domestic violence - also called Intimate partner violence (IPV) - and child intelligence at 8 year's old, using 3,997 mother child pairs from The University of Bristol's Avon Longitudinal Study of Parents and Children.

The study, funded by the Wellcome Trust and Medical Research Council, is published in Wellcome Open Research.

ALSPAC follows children from pregnancy, and measures emotional and physical domestic violence - also known as intimate partner violence - from pregnancy until eight years of age.

The intelligence of the children was measured at eight years using the Weschler standardised IQ test.

Dr Abel said: "We already know that 1 in 4 women age 16 and over in England and Wales will experience domestic violence in their lifetime and that their children are at greater risk of physical, social and behavioural problems.

"We also know that intelligence in childhood is strongly linked with doing well in adulthood, though there has been little evidence about the risk of low IQ for these children.

"While we cannot conclude that IPV causes low IQ, these findings demonstrate domestic violence has a measurable link, by mid-childhood, independent of other risk factors for low IQ."

17.6% of the mothers in the study reported emotional violence and 6.8% reported physical violence.

The findings are independent of other risk factors for low IQ such as alcohol and tobacco use in pregnancy, maternal depression, low maternal education and financial hardship around the child's birth.

There is some disagreement on whether the IQ test is a complete measure of intelligence, as it only considers verbal and non-verbal intelligence

However, it is regarded as useful by many experts because a high IQ has been demonstrated in many countries and cultures to associate with a broad range of improved social and health outcomes.

Dr Hein Heuvelman, from The University of Bristol added: "Exposure to domestic violence is common for children in the UK and an important and often overlooked risk factor in their life chances.

"So knowing the extent to which these already vulnerable children are further affected is a powerful argument for more, better and earlier intervention.

"Current support for women experiencing domestic violence is inadequate in some areas and absent in others.

"Early intervention with these families protects children from harm, but it may also prioritise their future development."

While estrogen receptor - + breast cancers express high levels of three anti-apoptotic Bcl-2 family members, pharmacological inhibition of Bcl-2 and/or Bcl-xL fails to induce cell death in ER + breast cancer cell lines, due to rapid and robust Mcl-1 upregulation.

Cells treated with a pharmacological inhibitor of cap-dependent translation, or with the mTORC1 inhibitor RAD001/everolimus, displayed reduced protein levels of Mcl-1 under basal conditions, and failed to upregulate Mcl-1 protein expression following treatment with ABT-263, a pharmacological inhibitor of Bcl-2 and Bcl-xL.

Dr. Rebecca S. Cook from Vanderbilt University, in Nashville TN, USA said, "The breast epithelium undergoes many dynamic changes throughout a woman's lifetime."

Specifically, anti-apoptotic Bcl-2 proteins either 1) bind to Bcl-2 effectors to block pore formation in the outer mitochondrial membrane caused by Bak/Bax oligomerization, or 2) sequester Bcl-2 activators, which facilitate Bak/Bax oligomerization.

Estrogen Receptor - positive breast cancer represents 60-70% of all breast cancers diagnosed.

Notably, up to 70% of ER+ breast cancers express Bcl-2, although Bcl-2 is expressed at low levels in other breast cancer subtypes.

In contrast, Bcl-xL and Mcl-1 are widely expressed in ER+ breast cancers, as well as in HER2-amplified and triple negative breast cancers, both in pre-malignant lesions and in high grade tumors.

Similarly, studies in pre-clinical models of ER + breast cancers showed that ABT-263 was ineffective as a single agent, in large part due to rapid Mcl-1 upregulation, although the molecular mechanism driving compensatory Mcl-1 upregulation in response to Bcl-2/Bcl-xL inhibition in ER+ breast cancers are not yet clearly defined.

The Cook research team concluded, "Importantly, we have tested the Mcl-1 selective inhibitor VU661013 in ER+ breast cancer cells, finding that Mcl-1 inhibition increases apoptosis and decreases tumor cell death, particularly when used in combination with ABT-263."