Hypothermia in organ donors could improve kidney transplants

The study, published in the New England Journal of Medicine, revealed that inducing a mild state of hypothermia in deceased organ donors reduced the likelihood of delayed graft function - whereby dialysis is required within 7 days of transplantation - in patients receiving kidney transplants by 38%.

At present, around 40% of kidney transplant recipients are reported to experience delayed graft function, which is linked with both increased medical costs and reduced long-term organ function.

"This is a free intervention that can be done at any hospital in the world, and tens of thousands of patients worldwide can benefit from it," states lead author Dr. Claus Niemann, professor of anesthesia and surgery at the University of California-San Francisco (UCSF).

Dr. Niemann believes their findings could have a major impact on global health and provide significant cost savings in the US through shorter hospital stays, less dialysis and potentially reducing the need for expensive interventions.

"In addition, it may allow us to consider organs we may otherwise reject, especially at the extremes of age, which would result in more patients benefiting from kidney transplantation," he adds. "This is of critical importance given we have a complete mismatch of transplant need and organ supply in the United States."

At present, an estimated 101,144 patients are awaiting kidney transplants, according to the US Department of Health and Human Services.

Targeted temperature management, also referred to as therapeutic hypothermia, is already used in the treatment of patients with stroke, asphyxia and certain types of cardiac arrest to preserve the function of the nervous system.

The researchers state that the effect of therapeutic hypothermia on protecting kidney function in transplantation has been uncertain, yet some studies have suggested that mild-to-moderate hypothermia could preserve renal function to some extent.

However, current transplantation protocols stipulate that the bodies of organ donors should be at normal body temperature, often leading to the bodies being actively warmed to ensure this.

Method could increase the number of kidneys available for transplantation

Dr. Niemann and colleagues conducted a randomized controlled trial involving a total of 370 organ donors. Of these, 190 were assigned to a group kept at normal body temperature and 180 were assigned to a hypothermia group, the bodies kept at around 2°C lower than the body temperature group.

A total of 572 patients received kidney transplants from the donors in the study - 287 from donors in the body temperature group and 285 from donors in the hypothermia group.

The researchers found that delayed graft function developed in 112 (39%) of patients receiving transplants from the body temperature group, compared with only 79 (28%) of patients receiving transplants from the hypothermia group.

As the intervention was demonstrated to be so successful, an independent data and safety monitoring board recommended an early end to the trial.

In particular, kidneys donated from older donors or donors with health issues that may have compromised their acceptance - also referred to as extended criteria donors - benefited from therapeutic hypothermia.

"From these findings, potentially more organs could be available for transplantation since we can push the limits with these 'marginal donors,'" explains Dr. Niemann. "This is critical because the number of available deceased organ donors has been stagnant, but the demand has dramatically increased. In the United States alone, about 101,000 patients wait for kidney transplantation."

In an accompanying editorial, Dr. Ina Jochmans and Dr. Christopher Watson identify some limitations of the study, noting that it does not provide any information on the potential longer-term effects on graft survival or what the effects on other organs are.

However, they state that the study's results will be welcomed, "not least of all because they have shown that, in this era of high-technology medicine and targeted drug therapy, it is still possible to identify a simple, cheap intervention that can have dramatic therapeutic effects."

Earlier this month, Medical News Today reported on a mouse study that found the body's "immune memory" of a rejected transplant may not be a permanent state, suggesting that subsequent transplants can be successful.

[Original Article]

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Prostate cancer can be categorized into five different types

The findings, published in the journal EBioMedicine, may have important clinical implication for the future. Doctors can now hope to identify which tumors are present in patient's body and if they are likely to spread aggressively and grow.

This new knowledge could open up the path to more tailoredcancer treatments.

Previously, prostate cancer could not be separated into subgroups. Due to this, treatments for the disease can often be inconsistent in effectiveness due to the wide range of reactions from patients.

Prof. Malcolm Mason, from Cancer Research UK, describes the difficulties of treating prostate cancer. He explains:

"The challenge in treating prostate cancer is that it can either behave like a pussycat - growing slowly and unlikely to cause problems in a man's lifetime - or a tiger - spreading aggressively and requiring urgent treatment. But at the moment we have no reliable way to distinguish them."

"This means that some men may get treatment they do not need," he continues, "causing unnecessary side effects, while others might benefit from more intensive treatment."

Prof. Mason says the findings could be "game-changing" if the same results are achieved in larger clinical trials. He explains:

"Ultimately this could mean more effective treatment for the men who need it, helping to save more lives and improve the quality of life for many thousands of men with prostate cancer."

Prostate cancer is the most common non-skin cancer in American men and is the second leading cause of cancer death among white, African-American and Hispanic men in the US.

The American Cancer Society predict 220,800 new cases of prostate cancer and 27,540 deaths from the disease this year.

Treatment could be tailored based on a specific tumor

In 2010, scientists discovered breast cancer to be at least ten different diseases, each with its own unique genetic signature, using an integrated genomic approach in stratifying disease.

It was this landmark study that prompted researchers from the Cancer Research UK Cambridge Institute and Addenbrooke's Hospital in the UK to investigate if the same techniques can be applied to prostate cancer.

The sample group consisted of 259 men, with samples of healthy and cancerous prostate tissue taken for examination. Scientists looked out for abnormal chromosomes and measured the activity of 100 different genes linked to the development of prostate cancer.

The study discovered five distinct types, each with a characteristic genetic fingerprint, much like the study in 2010 on breast cancer.

The method utilized by the study also proved to be more effective at predicting the most aggressive cancers, compared with the prostate-specific antigen (PSA) test and the Gleason grading system.

Study author Dr. Alastair Lamb, from the Cancer Research UK Cambridge Institute, hopes the findings here can be expanded to develop further our knowledge to treat the disease. He says:

"The next step is to confirm these results in bigger studies and drill down into the molecular 'nuts and bolts' of each specific prostate cancer type. By carrying out more research into how the different diseases behave, we might be able to develop more effective ways to treat prostate cancer patients in the future, saving more lives."

Medical News Today recently reported that management of the disease seems to have improved, according to a recent study. Health care professionals have encouraged a more "watchful waiting" approach as opposed to an aggressive treatment, such as surgery.

Although prostate cancer has affected millions, treatments for the disease are more effective than ever before. According to the most recent data, the 5-year survival rate for all stages of prostate cancer is 100%. The 10- and 15-year relative survival rates are 99% and 94%, respectively.

[Original Article]

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Exercise-mimicking molecule may offer new treatments for obesity, type 2 diabetes

The new molecule - called "compound 14" - was developed by Ali Tavassoli, professor of chemical biology at the UK's University of Southampton, and his research team.

Compound 14 works by blocking the function of a cellular enzyme called ATIC, which plays an important role in metabolism.

Blocking ATIC function leads to accumulation of a molecule called ZMP in cells, which activates cells' central energy sensor - called AMPK - causing them to think they are low in energy. As such, the cells attempt to boost energy levels by increasing metabolism and uptake of glucose.

For their study, Tavassoli and colleagues tested compound 14 on two groups of mice. One group was fed a normal diet while the other was fed a high-fat diet, making them obese and glucose intolerant - a sign of prediabetes.

Their findings were recently published in the journal Chemistry & Biology.

The team found that mice treated with compound 14 who were fed a normal diet retained a normal weight and blood glucose levels.

However, mice fed a high-fat diet who were treated with a single dose of the compound demonstrated a reduction in blood glucose levels, bringing them to near-normal.

In addition, when the mice fed a high-fat diet were given a single dose of compound 14 daily for 7 days, their glucose tolerance improved and they shed approximately 5% of their body weight.

The team notes that compound 14 did not lead to weight loss in mice fed a normal diet.

Compound 14 'holds much promise' as a therapeutic agent

Based on their findings, the researchers say compound 14 could lead to effective treatments for obesity - a condition that affects more than a third of adults in the US.

What is more, they say the compound could open the door to better treatments for type 2 diabetes, which accounts for 90-95% of all diabetes cases in the US.

"Current treatments for type 2 diabetes center on elevating circulating insulin levels or improving the insulin sensitivity of an individual," says study co-author Dr. Felino Cagampang, associate professor in integrative physiology at the University of Southampton.

"The issue is that established drugs do not successfully enable patients with type 2 diabetes to achieve glycemic control and some can even result in weight gain, a leading factor driving the diabetes epidemic," he continues. "In contrast, this new molecule seems to reduce glucose levels and at the same time decrease body weight, but only if the subject is obese."

The team plans to further develop compound 14, monitor its long-term treatment outcome and determine exactly how it improves glucose intolerance and achieves weight loss.

If the compound is found to be safe and effective, the researchers have high hopes that it could be used to create new drugs for the treatment of obesity and diabetes. Tavassoli adds:

"There is a lot of evidence from previous studies that if you could selectively activate AMPK with a small molecule, it could have potential benefits in the treatment of several diseases, including type 2 diabetes, by acting as an exercise mimetic and increasing the uptake and usage of glucose and oxygen by cells.

Our molecule, which activates AMPK by altering cellular metabolism, therefore holds much promise as a potential therapeutic agent."

Last month, Medical News Today reported on a study suggesting the bacteria Staphylococcus aureus plays a role in the development of type 2 diabetes among people who are obese.

[Original Article]

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Scientists identify another frequently mutated gene in melanoma

In describing their findings in the journal Nature Genetics, researchers from Yale University in New Haven, CT, hope they will lead to more targeted therapies for this most aggressive skin cancer.

Although melanoma is the least common skin cancer, it is responsible for the most deaths. The American Cancer Societyestimate that in 2015, around 73,800 Americans will discover they have melanoma and around 9,900 will die from it.

Melanoma starts in pigment-producing cells called melanocytes. While it is not clear exactly how it happens, it is thought that certain clusters of genetic mutations reduce a person's ability to resist the damage that ultraviolet (UV) radiation - such as that from the sun's rays - inflicts on the DNA in the cells. This damage affects certain genes that control how skin cells grow and divide, giving rise to tumors.

For their study, the Yale researchers used whole exome sequencing to analyze mutations in over 200 melanoma samples from patients with the disease.

The team - which included experts in genetics, pharmacology, cancer and computational biology - also ran experiments to see how tumor cells with particular mutations responded to anticancer drugs.

NF1 is a 'major player' in development of melanoma

The researchers confirmed that a gene called NF1 is a "major player" in the development of melanoma. In their paper, they note their analysis establishes NF1 as the "third most frequently mutated gene in melanoma, after BRAF and NRAS."

Lead and corresponding author Michael Krauthammer, an associate professor of pathology, also notes:

"The key finding is that roughly 45% of melanomas that do not harbor the known BRAF or NRAS mutations display loss of NF1 function, which leads to activation of the same cancer-causing pathway."

The analysis also reveals that the NF1 mutation mostly arose in samples from older patients with more mutations in their tumors. These include mutations in genes that affect the same signaling pathway, known collectively as RASopathy genes.

However, note the authors, while NF1 is the third most commonly mutated gene, on its own it does not cause cancer. A cluster of genetic changes, of which mutated NF1 is but one, is required to make a tumor.

Lead author Dr. Ruth Halaban, a senior research scientist in dermatology, concludes:

"Our study identified changes in about 100 genes that are present only in the malignant cells and are likely to be causative. This panel of genes can now be used in precision medicine to diagnose malignant lesions and can be applied to personalized cancer treatment."

The researchers also found that several factors, in addition to loss of NF1, can affect response to anticancer drugs, which Dr. Halaban says "opens the door to more research."

Funds from the National Institutes of Health, the Melanoma Research Alliance, Gilead Sciences and the Howard Hughes Medical Institute helped finance the study.

Earlier this year, Medical News Today learned of a study that found a quarter of healthy skin cells possess cancer-related mutations.

In the journal Science, researchers from the Wellcome Trust Sanger Institute explain how after examining skin samples from healthy people, they uncovered more than 100 cancer-associated mutations in every square centimeter of skin.

[Original Article]

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Nasal balloon could treat 'glue ear'

It is common for young children to be affected by otitis media with effusion (OME), whereby the middle ear becomes inflamed and filled with fluid that does not drain away as it should. While the condition can sometimes remain after an ear infection or lead to one, it does necessarily mean there is an infection.

OME, also referred to as "glue ear," often has no symptoms, but can affect hearing development, and sometimes it is only when parents notice this that they seek medical help.

According to the Agency for Health Care Research and Quality in the US, OME occurs commonly during childhood, with as many as 90% of children having at least one episode before their 10th birthday.

There is an urgent need to find new ways to deal with OME that avoid unnecessary and ineffective use of antibiotics, as co-author Ian Williamson, an associate professor in the faculty of medicine, explains:

"Unfortunately, all available medical treatments for otitis media with effusion such as antibiotics, antihistamines, decongestants and intranasal steroids are ineffective and have unwanted effects, and therefore cannot be recommended."

In the Canadian Medical Association Journal, the researchers describe how they undertook an open, randomized controlled trial to find out if the simple "nasal balloon autoinflation" procedure can be used on a large scale to treat children with OME in primary care settings.

During the procedure, the child blows through each nostril into a nozzle to inflate a balloon. This process sends air into the middle ear and helps return the pressure back to normal, clearing the built-up fluid.

The trial included 320 children aged 4-11 treated at 43 family practices in the UK. All participants had recent histories of OME and exams showed they had fluid in one or both ears.

Each child was randomly assigned to either a control group or a treatment group. The control group received standard care while the treatment group received standard care plus nasal balloon autoinflation three times a day for 1-3 months.

The results showed that children receiving autoinflation were more likely than the control group children to have normal middle-ear pressure after 1 month and 3 months.

After 1 month, 47% of children treated with autoinflation had normal middle ear pressure compared to 35.6% of the control group, and after 3 months these figures were 49.6% and 38.3% respectively. The children in the autoinflation group also had fewer days with symptoms.

'Effective alternative to surgery'

Prof. Williamson says the procedure is simple and inexpensive, and can be taught to young children in a primary care setting with a reasonable expectation that they will carry on and do it correctly at home. He notes:

"We have found use of autoinflation in young, school-aged children with otitis media with effusion to be feasible, safe and effective in clearing effusions, and in improving important ear symptoms, concerns and related quality of life over a three-month watch-and-wait period."

He and his colleagues suggest the autoinflation procedure should be offered more widely to children over the age of 4 to help them manage OME and reduce associated hearing loss.It is common for young children to be affected by otitis media with effusion (OME), whereby the middle ear becomes inflamed and filled with fluid that does not drain away as it should. While the condition can sometimes remain after an ear infection or lead to one, it does necessarily mean there is an infection.

OME, also referred to as "glue ear," often has no symptoms, but can affect hearing development, and sometimes it is only when parents notice this that they seek medical help.

According to the Agency for Health Care Research and Quality in the US, OME occurs commonly during childhood, with as many as 90% of children having at least one episode before their 10th birthday.

There is an urgent need to find new ways to deal with OME that avoid unnecessary and ineffective use of antibiotics, as co-author Ian Williamson, an associate professor in the faculty of medicine, explains:

"Unfortunately, all available medical treatments for otitis media with effusion such as antibiotics, antihistamines, decongestants and intranasal steroids are ineffective and have unwanted effects, and therefore cannot be recommended."

In the Canadian Medical Association Journal, the researchers describe how they undertook an open, randomized controlled trial to find out if the simple "nasal balloon autoinflation" procedure can be used on a large scale to treat children with OME in primary care settings.

During the procedure, the child blows through each nostril into a nozzle to inflate a balloon. This process sends air into the middle ear and helps return the pressure back to normal, clearing the built-up fluid.

The trial included 320 children aged 4-11 treated at 43 family practices in the UK. All participants had recent histories of OME and exams showed they had fluid in one or both ears.

Each child was randomly assigned to either a control group or a treatment group. The control group received standard care while the treatment group received standard care plus nasal balloon autoinflation three times a day for 1-3 months.

The results showed that children receiving autoinflation were more likely than the control group children to have normal middle-ear pressure after 1 month and 3 months.

After 1 month, 47% of children treated with autoinflation had normal middle ear pressure compared to 35.6% of the control group, and after 3 months these figures were 49.6% and 38.3% respectively. The children in the autoinflation group also had fewer days with symptoms.

'Effective alternative to surgery'

Prof. Williamson says the procedure is simple and inexpensive, and can be taught to young children in a primary care setting with a reasonable expectation that they will carry on and do it correctly at home. He notes:

"We have found use of autoinflation in young, school-aged children with otitis media with effusion to be feasible, safe and effective in clearing effusions, and in improving important ear symptoms, concerns and related quality of life over a three-month watch-and-wait period."

He and his colleagues suggest the autoinflation procedure should be offered more widely to children over the age of 4 to help them manage OME and reduce associated hearing loss.

Currently, in severe cases of OME, doctors perform a surgical procedure that cuts a hole in the ear drum in order to let the fluid drain.

In an article accompanying the study paper, Drs. Chris Del Mar and Tammy Hoffman from Bond University in Queensland, Australia, comment that:

"At last, there is something effective to offer children with glue ear other than surgery."

This study was conducted for Otovent - the makers of the balloon.

Meanwhile, Medical News Today has reported on another study that found an anti-stroke drug may be an effective treatment for middle ear infection, also addressing the urgent need for non-antibiotic treatments that reduce inflammation without side effects.

[Original Article]

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Evidence that Reston ebolavirus resides in live bats in the Philippines...

Update #1 18JUN2015

Jayme and colleagues find some
"smoking bats"-possible bat reservoir
species for Reston ebolavirus
in the Philippines.

In what I think is only the second example of this, a new collaborative study from Jayme and a team of eminent researchers in the Philippines, Australia, Vietnam and the United States, have reported the finding of Reston ebolavirus (RESTV) viral RNA and antibodies to viral infection in a range of different bat species....some more "smoking bats" - bats with more than just past evidence, sometimes considered vague and unreliable, of an ebolavirus being hosted by the animal.

The finding of RNA is not the same as actual infectious virus, but RNA is a very specific marker for the virus nonetheless. And the authors note that they didn't want to kill the bats so only a small volume of sample was available-not enough for culture.

Leroy and colleagues had previously reported finding Zaire ebolavirus RNA and antibodies against this species of virus in Hypsignathus monstrosus, Epomops franqueti and Myonycteris torquatebats, all fruit-eating megabats of the family Pteropodidae. These are considered to be important reservoir hosts, yet they do not show signs of disease.[2] 

According to one of the authors on the latest study, bats in the Philippines also seemed clinically well...

@MackayIM all bats we sampled appeared clinically healthy.

� Jonathan Epstein (@EpsteinJon) July 17, 2015

Locating the Philippine RESTV sequences
on the ebolavirus phylogenetic tree.
Jayme et al. Virology J. (2105) 12:107.[1]

Jayme's findings are important to the story of RESTV importations to animal facilities in the United States from the Philippines which occurred multiple times between 1989 to 1996. These fed into the dramatized retelling we know of as The Hot Zone. There were also signs of antibodies to the virus in humans working with infected non human primates in the Philippines in 1994, 1996 and 2008.

The amount of viral RNA in most of the bats was quite low - but was usually repeatably detectable. I'm a firm believer in PCR giving a specific signal when there is something specific present to detect (assuming it was done in a professional laboratory setting that reduces the risk of false positives-which it was in this instance). So low viral loads are not no viral loads.

RESTV RNA was repeatably found in oropharyngeal swabs taken from bats assigned to the following species:

• Cynopterus brachyotis (Lesser dog-faced fruit bat; range; fruit bat)
• Miniopterus australis (Little long-fingered or little bent-wing bat; range; insectivorous bat)
• Miniopterus schreibersii (Schreiber's Bent-winged Bat; range; insectivorous bat)

...and in one sample from:

• Chaerephon plicata (Wrinkle-lipped Free-tailed Bat; range; insectivorous bats)

What's particularly interesting to me is that some of these bat species are found in Australia. However, keep in mind that the range of some (?many) bats may be underestimated. The example here is using the IUCN Red List's described range for M. schreibersii-apparently it's a bat that inhabits an area around the Mediterranean.[4] Last I looked, the Philippines is a bit south of there. In the past, as Wikipedia lists, a much bigger range was ascribed to this bat, also including Australia,[5] Guinea, Liberia and Sierra Leone - among many others. Looks like there may be lots of work to do in the area of bat census.

Jayme and colleagues also sampled the blood of 61 flying foxes (of the fruit-eating bat family Pteropodidae) and antibodies were found by ELISA and Western blot in 3 Acerodon jubatus (giant golden crowned flying fox; range) bats and by ELISA alone in a Pteropus vampyrus (Large flying fox; range). If you trust the test, then this indicates past exposure.

Superman and the Joker know very well - Bats can be very tricky. But at least this finding helps to further address the Riddle(r) of the reservoir. Now, if only we could only nail down the specific culprit(s) in West Africa.

References...

1. Molecular evidence of Ebola Reston virus infection in Philippine bats
   http://www.virologyj.com/content/12/1/107?utm_content=bufferf022a&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer
2. Fruit bats as reservoirs of Ebola virus
   http://www.nature.com/nature/journal/v438/n7068/abs/438575a.html
3. Many details about bats to be found at the excellent IUCN Red List
   http://www.iucnredlist.org/
4. Population Structure of a Cave-Dwelling Bat, Miniopterus schreibersii: Does It Reflect History and Social Organization?
   http://jhered.oxfordjournals.org/content/100/5/533.full
5. Seasonal movements of the Schreibers� bat, Miniopterus schreibersii, in the northern Iberian Peninsulahttp://www.tandfonline.com/doi/abs/10.1080/11250000801927850#.Vamrtvnzp1M

Updates...

1. Added bat specie range data (and discussion) from IUCN Red List and Wikipedia.

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