An expert is one who knows more and more about less and less until he knows absolutely everything about nothing

Showing posts with label Up to Date. Show all posts
Showing posts with label Up to Date. Show all posts

Friday, March 9, 2018

ACP Recommends Less-Intensive HbA1c Target for T2D No proof of benefit for targets below 7%, new guidelines say

New type 2 diabetes guidelines from the American College of Physicians (ACP) recommend less-intensive blood sugar control for most patients, with a glycated hemoglobin (HbA1c) target between 7% and 8%.
"Studies have not consistently shown that intensive glycemic control to HbA1c levels below 7% reduces clinical microvascular events, such as loss or impairment of vision, end-stage renal disease, or painful neuropathy, or reduces macrovascular events and death," said first author Amir Qaseem, MD, PhD, ACP vice president for clinical policy, and colleagues.
To develop the new recommendations, the authors evaluated six sets of current guidelines from other organizations and reviewed five important clinical trials on which those guidelines are based. The updated guidance, published online in Annals of Internal Medicine, offers four key statements:
  • Statement 1: Clinicians should personalize goals for glycemic control in patients with type 2 diabetes on the basis of a discussion of the benefits and harms of pharmacotherapy, patients' preferences, patients' general health and life expectancy, treatment burden, and costs of care
  • Statement 2: Clinicians should aim to achieve an HbA1c level between 7% and 8% in most patients with type 2 diabetes
  • Statement 3: Clinicians should consider de-intensifying pharmacologic therapy in patients with type 2 diabetes who achieve HbA1c levels less than 6.5%
  • Statement 4: Clinicians should treat patients with type 2 diabetes to minimize symptoms related to hyperglycemia and avoid targeting an HbA1c level in patients with a life expectancy less than 10 years due to advanced age (80 years or older), residence in a nursing home, or chronic conditions (such as dementia, cancer, end-stage kidney disease, or severe chronic obstructive pulmonary disease or congestive heart failure) because the harms outweigh the benefits in this population
Qaseem et al reviewed and scored currently available guidelines using the AGREE II(Appraisal of Guidelines for Research and Evaluation II) instrument. This tool asks 23 questions about central aspects of recommendations, including their scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence. The authors scored each guideline independently, and then compared the scores.
The two lowest-scoring guidelines were from the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) and the American Diabetes Association (ADA). Both scored lowest on stakeholder involvement, applicability, editorial independence, and scientific rigor.
"Several factors were important in considering guideline quality," the authors said. "For example, although many guidelines described benefits, adverse effects, and the strength and limitations of evidence or linked the evidence to the recommendation, they often inadequately described how they had considered or weighted these factors in developing the final recommendations. The guidelines frequently relied on selective reporting of studies or outcomes and focused on relative versus absolute effects and asymptomatic surrogate measures rather than patient-centered health outcomes."
The five clinical trials reviewed were:
  • ACCORD (Action to Control Cardiovascular Risk in Diabetes)
  • ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation)
  • VADT (Veterans Affairs Diabetes Trial)
  • Both UKPDS (United Kingdom Prospective Diabetes Study) trials
"Collectively, these trials showed that treating to targets of 7% or less compared with targets around 8% did not reduce death or macrovascular events over about 5 to 10 years of treatment but did result in substantial harms, including but not limited to hypoglycemia," the authors wrote. "No trials show that targeting HbA1c levels below 6.5% in diabetic patients improves clinical outcomes, and pharmacologic treatment to below this target has substantial harms."
The ACP recommendation to de-escalate therapy in patients who achieve HbA1c levels less than 6.5% is notably different from other guidelines, said David Lam, MD, of Icahn School of Medicine at Mount Sinai in New York City, in a statement. "This may change how some providers care for patients who are able to achieve this level of control. However, it is important to also consider what potential impact the subsequent increase in HbA1C level may have on the patient's quality of life and their perception of overall health."
The recommendation against a specific HbA1C target in patients with limited life expectancy and multiple comorbidities is another difference, he continued. "While many providers likely already adjust their A1C goals in this subset of patients, this guideline may further change the care in this group of patients."
Qaseem and co-authors concluded: "The ACP believes that clinicians should reevaluate HbA1c levels and revise treatment strategies on the basis of changes in the balance of benefits and harms due to changed costs of care and patient preferences, general health, and life expectancy."

Sunday, July 17, 2016

Novel Therapeutic Advances for Management of Diabetes Mellitus

Diabetes mellitus (DM) has become one of the most challenging health problems in the 21st century. It is a serious public health problem globally, but the good news is that various advances are being made in prevention, detection, and treatment of diabetes. Though prevention is always better than cure, yet sometimes prevention is not possible and the cure seems to take ages. The interest to find a possible cure for diabetes has eventually led to exploration of various new scientific areas of research.
Volanesorsen (formerly ISIS-APOCIIIRx)is an antisense drug in development intended to treat patients with severely high triglycerides either as a single agent or in combination with other triglyceride-lowering agents.Elevation in triglycerides has always increased the risk of cardiovascular disorders as well as type 2 diabetes mellitus (T2DM). Researchers from the University of Pennsylvania have found the therapeutic effect of lipid-lowering medication sin improving insulin sensitivity in people with T2DM. Volanesorsen is an oral medication that can help to control the blood sugar levels. Itis believed to improve the insulin sensitivity and significantly decrease the patients’ overall glycated hemoglobin (HbA1c). After taking the medication for 12 weeks, researchers found that adult T2DM patients receiving volanesorsen experienced 69% reduction in triglycerides, and 57% improvement in whole-body insulin sensitivity.Researchers concluded that decrease in triglycerides was strongly related to improved insulin sensitivity and improved HbA1c.
PEGylated Lispro
PEGylated lispro (LY2605541) has been developed by the addition of polyethylene glycol (PEG) to insulin lispro, leading to its extended half-life. Early phase evaluations of PEGyalted lispro confirm its non-inferiority to glargine with a potential weight advantage when used in T2DM. Since insulin therapy is anabolic and its initiation is commonly associated with weight gain, an insulin preparation associated with a beneficial weight profile would represent a particularly valuable therapeutic entity.
Pre-clinical studies indicate that LY2605541 has low mitogenic potency, exerting a preferential hepatic effect on glucose homeostasis. However, LY2605541 appears to cause elevated transaminases and derangement of lipid profiles. On the basis of these initial observations, LY2605541 requires further extensive clinical evaluation to fully assess its risk/benefit profile in the management ofdiabetes.
Islet Transplantation
A novel technology has been developed to help treat type 1 diabetes mellitus (T1DM) and potentially negate the need for insulin injections. Islets are organoids that produce multiple hormones, including insulin, and donated islets are already treating severe cases of T1DMeffectively. Islet transplantation can transform the lives of T1DM patients, and may result in long-term freedom from insulin injections with excellent glucose control.
Natural Products
Plants possessing antidiabetic properties may be suitable as an adjunct to the existing therapies or as a prospective source of new hypoglycemic compounds. Many new bioactive drugs isolated from plants demonstrate antidiabetic activity equal to known oral hypoglycemic agents such as tolbutamide and chlorpropamide. Several plant species with terpenoids, flavonoids, phenols, coumarins, and other bioactive constituents have shown their potency in reducing blood glucose levels. Plants likeAllium sativum(Liliaceae),Gymnema sylvestre(Asclepiadaceae),Murraya koenigii(Rutaceae),Allium cepa(Liliaceae),Withania somnifera (Solanaceae), andFerula foetida (Umbelliferae) have exhibited antidiabetic properties when assessed in experimental models of diabetes. These traditional approaches might prove to bebeneficial in treatment of diabetic complications.
Great strides have been made clinically in the management of diabetes. Extensive research may lead to discovery of newer and better options for diabetes. With new technologies revolutionizing the treatment possibilities, the search for an effective medication is not far ahead.
Turacoz Healthcare Solutions aims to create awareness for such healthcare issues like diabetes mellitus which pose a serious threat to people, irrespective of race, gender, or age. We consider it our corporate responsibility to share the knowledge related to therapeutic research and development, and keep you updated with the recent medical advancements in the healthcare industry.“Being aware of a disease and its deleterious consequences”is the first-step towards its prevention. So stay healthy and stay long.

Saturday, March 19, 2016


A petite 44-year-old woman has become the first patient in the world to be bridged to a successful heart transplant, that is, to go from needing a transplant to receiving one, with an experimental Total Artificial Heart designed for smaller patients.  The UCLA patient received a successful heart transplant at Ronald Reagan UCLA Medical Center, thanks to the smaller Total Artificial Heart.
The team explain that the 50cc SynCardia temporary Total Artificial Heart is a smaller investigational version of the larger 70cc SynCardia heart, which was approved for use in people awaiting a transplant by the Federal Food and Drug Administration in 2004 and has been used by more than 1,440 patients worldwide.  They go on to add that the 50cc device is designed to be used by smaller patients, including most women, some men and many adolescents, with end-stage biventricular heart failure, where both sides of the heart are failing to pump enough blood to sustain the body. The device provides mechanical support until a donor heart can be found.
Nemah Kahala, a wife and mother of five, was transferred to UCLA from Kaiser Permanente Los Angeles Medical Center in March. She was suffering from restrictive heart muscle disease and in critical condition. Her heart failure was so advanced that repair surgery and other mechanical assist devices could not help.  Nemah was placed on a life support system called extra corporal membrane oxygenation, however, the team note that this only works for about 10 days before a person’s organs begin to deteriorate.
With the clock ticking, doctors needed to buy time by replacing Nemah’s failing heart with an artificial heart while she waited for a heart transplant. Her chest cavity was too small for her to receive the larger 70cc artificial heart. However, under a one-time emergency use permitted under FDA guidelines, her doctors were able to implant the experimental 50cc device.
Her surgeons explain that Mrs. Kahala’s condition was deteriorating so rapidly that she would have not survived while waiting for a transplant. The team were therefore grateful to have this experimental technology available to save her life and help bridge her to a donor heart.
The researchers state that the artificial heart provides an immediate and safe flow of blood to help vital organs recover faster and make patients better transplant candidates.  After the two-hour surgery to implant the artificial heart, Nemah remained hospitalized in the intensive care unit and eventually began daily physical therapy to help make her stronger for transplant surgery.
Two weeks after the total artificial heart surgery, she was strong enough to be placed on the heart transplant list. After a week of waiting, a donor heart was found.
In addition to the high-tech medicine that kept the patient alive, Mrs. Kahala and her family have exemplified how a solid support system that includes loved ones and a compassionate medical team practicing what we at UCLA have termed ‘Relational Medicine’ plays an important role in surviving a medical crisis.
Since 2012, the UCLA Heart Transplant Program has implanted eight 70cc SynCardia Total Artificial Hearts. UCLA also participated in the clinical study of a 13.5-pound Freedom portable driver, a backpack-sized device that powers the artificial heart, allowing the patient to leave the hospital , that received FDA approval on June 26, 2014.
Nemah was discharged from UCLA on April 18. She is grateful to be home in Riverside with her family, who own a grocery store in the city of Orange.

The SynCardia Total Artificial Heart, at left, and a human heart, at right. Credit: SynCardia 2015

Source:  UCLA university of California 


A great year for health innovations with exciting discoveries, verification, validations and breakthroughs.  The big disease areas are still cancer, heart disease, diabetes and Alzheimer’s, however, it’s the methodology of detection, imaging, and the descriptive diagnostics that have been innovated this year.  In some cases these disciplines and techniques bleed through to multiple disease areas as other teams pick up the technology.  A common thread running through all of these areas however, is the all important biomarker.  And with each newly discovered biomarker comes the benchmark and standardisation. A new receptor, more inroads in stem cell technology and regenerative medicine, all leading back to control and revamping of our own DNA and a big push in immunology.
We saw the definitive breakthrough that is precision genetics with the evolution of personalized medicine into precision medicine; becoming more precise and honed, moving into master regulator genes as opposed to the confusing multiple loci and the personal immunity simulation of the past.  The medical community theorizing and validating that the mass of loci being targeted were in fact the resulting cascade of these precisely hit master genes.  This big push in genetics with researchers giving clarification, gaining a clear direction in sequencing and beginning to classify epigenetic methylation.
With epigenetic methylation research teams are now beginning to map and classify cancer via the epigenome. Reaching the source of all disease, that moment of mutation, the moment of epigenetic methylation; that clear crystalline moment when disease is born.  Medical teams around the world have summised that all disease comes from nuclei, is ordered by the gene and transcribed through the MiRNA; still an important area, to the moment of epigenetic methylation.  The moment that our DNA is changed forever and the cascade of disease-causing loci and proteins begin.
Health innovators have also taken a step back even further in the source and began to chip away at the facade of neurogenetics.  The genetic code held in our brain, the regulator of not only diseases and disorders of the brain but also  disease within the body.  This leads on nicely to the great inroads being made in neuroinnovations, standardised and medicalised, this area holds many answers to the questions the medical community have been asking for decades.  When we finally map every circuit, every pathway, all neurogenetics, it is expected to lead to the man-made regulation of all disease.  And with neuroscience this need not always be invasive.
Neuroinnovations have been astounding this year with multiple validated studies medicalising diagnostics, representing disease of the brain in terms in which all disease should be presented, in scans, in blood work, in genetic terms.  We have also witnessed a big drive to uncover more about the role the lesser-known cells, such as Astrocytes, play in the brain as well as the surrounding microglia in the hope this will lead to a crack in the looming blood-brain-barrier.  And most importantly the medical community has been given more control over the disorders we now understand to be more than emotive figments of imagination; more control to help with tangible and very real mental disorders which have now been imaged, seen with the naked eye in blood work and designated the correct biomarkers.
So, what were the biggest healthinnovations of 2014? What did health innovators concur on this year?  Which disease areas, disciplines and techniques were of the most interest to health innovators across the globe and were seen as the biggest breakthroughs, raising the most interest?
So here you go health innovators, here are the Top 10 Healthinnovations of 2014 based on the total number of views and shares:
1.  At number one we have the Karolinska Institutet of Sweden, whose breakthrough
neuroscientific human study lays the foundation for neurogenetic study in neuroplasticity.  This study identified the cells responsible for the superior plasticity of the human brain, the oligodendrocyte otherwise known as myelin.  Here we saw researchers modulate myelin production, with potential to fight TBI, MS, enhance plasticity, enhance brain processes, memory, fight dementia, whilst opening a door to neuroprotection.  Neurologically-wise this study has it all.  We are seeing a sharp increase in non-neuronal studies in the brain with researchers investigating the role of these lesser-known brain cells.  The number one study also provides detailled knowledge on the brain cell in question, oligodendrocytes.  They were able to establish, through, histological studies that at birth most oligodendrocytes are immature. The study then goes on to tell us what age we are when oligodendrocytes reach maturity and their turnover rate thereafter. The researchers were even able to carbon-date the cells and determine their age which is why this is the most viewed and shared Healthinnovations of 2014.
2.  At number two we have is the National University of Singapore of Singapore, who found a new type of immune cell that is expected to help in the development of a future treatment for Multiple Sclerosis (MS).  The study also explores the role of the all-important interleukin pathway, a very hot area at the moment, in the immune system.  The team found that a new type of immune T helper cells named TH-GM cells play a crucial role in the immune system and pathogenesis of neuronal
inflammation. The team showed that STAT5, a member of the STAT family of proteins, programs TH-GM and initiates the immune response to an auto-antigen in responding to a signal from an interleukin, IL-7, causing neuroinflammation, pathogenesis and damage in the central nervous system. Thus blocking IL-7 or STAT5 would provide a significant therapeutic benefit for Multiple Sclerosis (MS).
3.  Coming in next at number three St Vincent’s Hospital and the Victor Chang Cardiac Research Institute of Australia, who transplanted an already dead heart in a world’s first.  This breakthrough firmly pushed the human race out of the age of regeneration hurtling into the aeon of reanimation.  Surgeon’s developed a technique which means hearts that had been still for 20 minutes can be resuscitated and
transplanted into a patient.  The technique involves donor hearts being transferred to a portable machine known as a ‘heart in a box’ in which they were placed in a preservation solution, resuscitated and kept warm.  So far three people have received hearts in this way, with this novel transplant system expected to save 30 percent more lives by providing more hearts, which were in the past deemed unsuitable and/or too starved of oxygen to transplant.
4.  At number four is the Hebrew University of Jerusalem of Israel and the Max Dellbruck Institute of Germany.  The team not only discovered how the recently discovered circular RNA is formed they also identified a key muscular dystrophy link.  Unlike all other known RNAs, this molecule is circular, and is labelled circular RNA.  The team found that circRNAs not only compete with normal
RNAs, but the body actually produces them at the expense of normal RNA. The researchers observed that circRNAs play an important role in brain function, and likely in brain disease.  In addition, the researchers identified the protein ‘muscleblind’ as a factor involved in circRNA biogenesis, and showed that muscleblind can enhance and regulate the production of a subset of circular RNAs.  Importantly, defects in muscleblind function are known to cause a severe degenerative disease called myotonic dystrophy. Characterized by progressive muscle wasting and weakness, this is the most common form of muscular dystrophy that begins in adulthood.
5.  At the midway mark, at number five, we have the University of California, Los Angeles (UCLA), of the United States of America.  The team utilized a novel technology called electric field-induced release and measurement (EFIRM) to test lung cancer patients’ saliva for epidermal growth factor receptor (EGFR) gene mutations, a sign of lung cancer, which can be treated by medication
such as thymidine kinase inhibitors. The total detection time is less than 10 minutes and only requires a small saliva sample.  EFIRM is a multiplexible electrochemical sensor which uses electrode chips to enable exosomes in saliva to rapidly release molecular constituents (DNA, RNA and proteins) while simultaneously detecting any mutations in tumour-causing DNA sequences.  So here is a cancer detection study hitting all the marks, precision genetics, non-invasive testing, epigenetic mutation/methylation markers for cancer and a new spectra method. And of course that all important new biomarker.
6. Coming in at number six we have a multi-centre study led by the University of California of the United States of America.  This study reminded the medical community how important verification
and building on initial discovery is in making past findings standardised for usage in mass clinical settings.  Here the team provided the first evidence of the medium- to long-term safety and tolerability of transplanting human embryonic stem cells (hESCs) in humans.   This important benchmark also provided set hESCs dosages when treating human macular degeneration with stem cell therapy.
7.  At number seven we have the University of Connecticut, of the United States of America.   The team found a new way to identify protein mutations in cancer cells to develop the first precision medical vaccine to treat patients with ovarian cancer.  This vaccine is so precise that it can recognise tiny differences and mistakes on a cancer cell’s surface epitopes, thus allowing the cancer ‘vaccine’ to attack and kill the cancer cell.  In this way the
surrounding healthy cells with normal epitope sequences are ignored and left intact.  These subtle epitope mutations come from incorrect epigenetic methylation when cancer cells proliferate, making this a best-in-class when it comes to precision genetics and medicine.
8.  Nearing the end of this great list we have the Lund University of Sweden, McGill University of Canada and theHeart and Stroke Foundation of Canada at number eight.  This large-scale study  linked the genetic predisposition to elevated low-density lipoprotein cholesterol (LDL-C) to aortic
valve calcium and narrowing of the aortic valve.  This study was also valuable due to the fact there are 35,000 participants providing strong, instant validation for this new discovery.  Any team in the future will find validation an easy job with this study giving it an easy path into clinical procedure.  The data suggests that, in addition to the established risks for myocardial infarction and other vascular diseases, increases in low-density lipoprotein cholesterol are also associated with increased risk for aortic stenosis.  The team now plan to investigate whether intervention to reduce low-density lipoprotein cholesterol could prevent aortic valve disease.
9.  At number nine of the Top Ten Health innovations of 2014  we have the Salk Institute and Harvard Medical School of the United States of America.  Very few studies assimilate the spinal
chord and brain as one entity let alone map new spinal chord-to-brain neural mechanisms and receptors for chronic pain.  The researchers set out to precisely identify the spinal neurons involved in these circuits. They deciphered the role each of the two neuronal cell types, pain receptors and touch receptors, play in the processing of pain signals in the dorsal horn, the location where the sensory neurons connect with the spinal chord. The findings of this study are expected to help find new targets and treatments for the people who suffer from chronic pain as well as allodynia, fibromyalgia and nerve damage caused by diseases such as diabetes, cancer and autoimmune disorders as well as physical trauma.  As new technology and diagnostics become more available to the neuroscientific community these rich neurobiological studies, whereby more vital neuroanatomy is discovered, are greatly anticipated and received.
10. And at number ten we have Boston University of the United States of America and the United States Army, with a genetically-based breakthrough for Ebola.  One of the greatest concerns about this killer disease is the conjecture over the time of contagion.  The general consensus is that
Ebola only becomes contagious once a fever breaks with opponents stating that this is only because the fever is the onset of vomiting, unexplained bleeding and/or diarrhea, ie. excessive bodily fluid-loss.  Thus the existing argument is that although the incubation period of Ebola can be as long as three weeks, this excessive loss of Ebola-infected bodily fluid grossly raises the level of potential contamination and infection.  The researchers put paid to this argument by providing an RNA-based assay which can distinguish between different hemorrhagic fevers, including Marburg (Ebola cousin) and Lassa before the person becomes symptomatic, at the point the virus enters the blood stream.  As the test includes the cousin of the Ebola hemorrhagic virus, the Marburg hemorrhagic virus, it is hoped that the test can be tweaked to include Ebola.

Sensitive Blood Test May Help Rule Out Heart Attack

WEDNESDAY Oct. 7, 2015, 2015 — A new, highly sensitive blood test may help doctors quickly rule out heart attack for almost two-thirds of people who seek emergency room treatment for chest pain, a new study suggests.
Researchers said their findings could potentially reduce unnecessary hospital admissions and substantially lower health-care costs. “Until now, there were no quick ways to rule out a heart attack within the emergency department,” said the study’s lead author, Dr. Anoop Shah, from the University of Edinburgh in Scotland.
“Over the last two decades, the number of hospital admissions due to chest pain has tripled. The overwhelming majority of these patients do not have a heart attack,” Shah said. Assessing a possible heart attack requires lengthy stays in the ER or hospitalization for repeat testing, the study authors pointed out.
The new test is more sensitive than the standard version, Shah’s team said. It can detect far lower blood levels of troponin, a protein released when heart muscle is damaged. The more damage that occurs, the higher blood levels of troponin will be. A slight increase in troponin suggests some damage has occurred, while very high levels indicate a person has had a heart attack, the researchers explained.
Using this new test, doctors could potentially double the number of low-risk patients able to be safely discharged from the emergency room, the researchers reported in the Oct. 8 issue ofThe Lancet.”Use of this approach is likely to have major benefits for both patients and health-care providers,” Shah said in a journal news release.
For the study, the researchers measured troponin levels in more than 6,000 patients admitted to the hospital with chest pain, and assessed their risk for heart attack and death from heart attack within 30 days.
The investigators found that 61 percent of the patients with a troponin level below 5 ng/L (nanograms per liter of blood) were at very low risk of heart attack and could have been discharged early, regardless of age, gender, and risk factors for heart disease. One year out, these patients had a three times lower risk of heart attack and cardiac death than those with higher troponin levels, the researchers said.
The authors of an accompanying editorial in the journal said patient follow-up will be needed to validate use of this test in routine practice.”Trials are needed to assess the safety and effectiveness of clinical pathways that involve no further testing for such patients,” wrote Martin Than from Christchurch Hospital, New Zealand, and colleagues.

More information
The American Heart Association describes the symptoms of heart attack.

Insight into cancer resistance in elephants could aid human treatment !!!!

They are the largest land animals in the world, weighing up to 14,000 pounds and standing up to 4 meters tall. Given their size, elephants should be highly susceptible to cancer – they have at least 100 times more cells than humans – but they rarely develop the disease. In a new study, researchers shed light on the mechanisms behind elephants’ resistance to cancer – information that could fuel knowledge on cancer resistance in humans.
Study leader Dr. Joshua D. Schiffman, of the University of Utah School of Medicine, and colleagues publish their findings in JAMA.
Theoretically, an animal’s cancer risk should increase with their size and lifespan; the bigger an animal is, the more cells they have, which should increase the rate of cell division and susceptibility to gene mutations.
In 1975, however, a study by Dr. Richard Peto, of the University of Oxford in the UK, challenged this notion. He observed that cancer incidence across species is not dependent on an animal’s size or lifespan – a theory that is now hailed “Peto’s Paradox.”
A good example of this theory is the disparity in cancer incidence between humans and elephants; despite elephants being significantly larger than humans, their risk for cancer is much lower.
Previous research has suggested that specific molecular mechanisms in elephants protect them against cancer, though Dr. Schiffman and colleagues note that such mechanisms are poorly understood.
For this latest study, the team set out to learn more about the disparities in cancer mortality rates across different mammals, with a specific focus on elephants, and to shed light on possible mechanisms that induce cancer resistance in different species.
The researchers assessed information on disease and cause of death for 36 mammalian species, including African or Asian elephants.
The genomes of all species were assessed, as well as the activity of peripheral blood lymphocytes – a type of white blood cell – among elephants, healthy humans and patients with a disease called Li-Fraumeni syndrome (LFS), a rare inherited condition that greatly increases the risk for cancer. This was to assess response to DNA damage.
Overall, the researchers found that cancer mortality rates did not increase with the size or lifespan of a mammal. For example, the cancer mortality rate for elephants was only 4.8%, compared with an 11-25% cancer mortality rate in humans.
The team also revealed that elephants possess at least 20 copies of a major tumor-suppressor gene called TP53, while healthy humans only have one copy, with two alleles (gene variants) inherited from each parent. People with LFS only inherit one functioning allele of the TP53 gene, according to the team, putting them at a 90-100% lifetime risk for cancer.
The researchers explain that the TP53 gene plays a key role in the response to DNA damage by triggering a form of cell death called apoptosis via the p53 protein. Compared with human lymphocytes, the researchers found that elephant lymphocytes were subject to p53-induced apoptosis at higher rates.
Based on their findings, the team suggests the additional copies of the TP53 gene and increased p53-induced apoptosis in elephants have evolved to protect them against cancer.
The authors write:
“Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage.
These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression.”
In an editorial linked to the study, Mel Greaves, PhD, of the UK’s Institute of Cancer Research, says the theory that elephants may be protected against cancer due to the acquisition of multiple copies of the TP53 gene seems “plausible.”
However, Greaves notes that it is unclear what implications the findings have for cancer in humans. “Perhaps the main message from this innovative investigation is to bring into focus the question of why humans appear to be so ill-adapted to cancer, given the average size and life span,” he speculates.
“The human genome is replete with footprints of positive selection in the not-too-distant historical past. Humans may have acquired, in one particular respect, an extra cancer suppressor gene variant early on in evolutionary history approximately 1.8 million years ago,” Greaves continues.
He points out, however, that modern humans are particularly vulnerable to cancer, which is more down to lifestyle factors – such as smoking – that are not seen in other animals. “These behaviors are relatively recently acquired by humans, over a few hundred years, and the risks they impart far exceed prior and otherwise effective cancer suppressor mechanisms that were inherited from primate ancestors,” explains Greaves.

HRT safe and perhaps beneficial in women treated for ovarian cancer, major trial shows

Women with the commonest type of ovarian cancer can safely take hormone replacement therapy (HRT), and it could have a beneficial effect on their survival, a long-term clinical trial reports.The 24-year, phase III international trial provides the strongest evidence yet that women with epithelial ovarian cancer – which accounts for 80-90 per cent of cases – can safely take HRT during or after their treatment.
Several major studies have found that HRT can increase the risk of developing some cancers, which is why there has been such interest in whether it is safe to take during cancer treatment.
The new study, published in the Journal of Clinical Oncology, was led by researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, and is the largest to investigate HRT’s effects on ovarian cancer survival.
It was funded by The Institute of Cancer Research and Cancer Research UK, and endorsed by the UK Co-ordinating Committee for Cancer Research.
Set up in 1990, the trial followed 150 women with epithelial ovarian cancer – half of whom were allocated to receive HRT during their treatment, and half of whom were not – and compared overall survival at a point in 2012, 22 years after the trial began.
Women were recruited from 19 different hospitals across the UK, Spain and Hungary, in a study co-ordinated by researchers at The Institute of Cancer Research (ICR).
53 of the 75 women (71 per cent) in the HRT arm of the trial – who were allocated to receive HRT for up to five years after the study began – had died, compared with 68 (91 per cent) of the 75 women who had not taken HRT.
The results are relevant to a large proportion of women with ovarian cancer because ovarian cancer treatments can trigger the menopause.
The study suggests that women with ovarian cancer can receive the known benefits of HRT on the side-effects of the menopause, without it reducing their survival chances. In fact, the results indicate that HRT might improve chances for overall survival.
The trial looked at women who already had ovarian cancer. Years of research have already shown that when healthy women take HRT their risk of developing breast, ovarian and possibly womb cancer can increase.
Study clinical lead Professor Ros Eeles, Professor of Oncogenetics at The Institute of Cancer Research, London, and Consultant at The Royal Marsden NHS Foundation Trust, said:
“We were really happy to be able to show that HRT is safe for women with the most common type of ovarian cancer. Whether or not to have HRT is a very important decision for a large proportion of women with ovarian cancer, who will often have to undergo the menopause due to the cancer treatment at the same time as coping with a cancer diagnosis.
“Our results not only suggest HRT is safe for women with this type of ovarian cancer, but that it may actually improve their chances of long-term survival. We hope our study will inform treatment for women with ovarian cancer, and the findings could have a big impact on their quality of life.”
Study scientific lead Professor Judith Bliss, Director of the Cancer Research UK-funded Clinical Trials & Statistics Unit at The Institute of Cancer Research, London, said:
“Our results should provide some reassurance to women with ovarian cancer who until now might have avoided HRT because of worries about its effect on their cancer. HRT does not seem to have a detrimental effect on survival in women with epithelial ovarian cancer, and there is even the intriguing suggestion that it may be improving their survival chances. We would like to see more research into this area in the future and hope to see other studies confirm this finding in larger numbers of women.”
Fiona Osgun, health information officer at Cancer Research UK, said:
“Years of research has shown that women taking HRT are at an increased risk of breast and ovarian cancer, as well as endometrial cancer for some forms of HRT. This research takes a different approach and looks at women already diagnosed with ovarian cancer.
“These results are a great first step in helping to understand if HRT is safe to take for women with ovarian cancer, but we need larger studies with more women to confirm them. HRT has been shown to be effective at reducing symptoms of the menopause and there are many factors that play into a woman’s decision to use it or not. If you are thinking of stopping or starting HRT speak to your GP.”

For more information please contact the ICR press office on 020 7153 5582 / For enquiries out of office hours, please call 07595 963613.
Source: EurekAlert! 9/28/15

Sunday, March 6, 2016

When will the law change to decriminalize doctor-assisted deaths?

When will the law change to decriminalize doctor-assisted deaths?
The Supreme Court of Canada gave the government of Canada one year to draft new laws, if it wishes, to govern physician-assisted death. In a legal sense, Parliament could just do nothing; politically, though, that is highly unlikely, as the Conservative government would be seen as abdicating its duty to Canadians.
If Parliament approves no new law on assisted death by next February 6th, the law would change on that date to permit assisted dying for some suffering adults. This is a very serious right — control over one’s life covering what the court called “the passage into the death.” It can’t be held back by government inaction. Government can’t limit this right more than the court will allow.
The government has not publicly said whether it will introduce and try to pass a new law before the election. “This is a sensitive issue for many Canadians, with deeply held beliefs on both sides,” Clarissa Lamb, a spokeswoman for the federal Justice Department, said in an email. “We will thoroughly and thoughtfully study the Supreme Court’s decision . . . and ensure all perspectives on this difficult issue are heard. We will consult widely with Canadians and review the decision comprehensively before deciding how to respond.”
The Supreme Court set the parameters for any new law on physician-assisted death for ill people, and they are wide. They do not just cover the terminally ill. And “intolerable” suffering needs to be seen through the eyes of the ill individual. This group includes those who are suffering psychologically. The court said that the assisted-suicide laws currently on the books will not be considered valid “to the extent that they prohibit physician-assisted death for a competent adult person who (1) clearly consents to the termination of life and (2) has a grievous and irremediable medical condition (including an illness, disease or disability) that causes enduring suffering that is intolerable to the individual in the circumstances of his or her condition.”
Provincial governments, too, may wish to draft laws on assisted dying, since health care is a shared responsibility with Ottawa. Quebec already has drafted one such law, which was almost certain to be found unconstitutional if the court had upheld the Criminal Code provisions on assisted suicide; the constitution bars provinces from legislating in areas covered by the criminal law, which is exclusively federal jurisdiction. As it is, the Quebec law on assisted death would likely run afoul of the Supreme Court ruling, in that it applies only to the terminally ill.
The February 6, 2016 deadline poses a challenge for the federal government, as summer recess is coming and an election is expected next October. Some had suggested the Justice Department would ask the court for an extension, but that seems highly unlikely, and it is not difficult to imagine how the court would treat such a request.

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team of researchers have identified a gene that drives one of the most aggressive forms of breast cancer. They hope that by finding a way to block the gene they may be able to make the cancer less aggressive.In their study, published in Nature Communications, the researchers found that the gene known as “inhibitor of differentiation 4” (ID4) not only indicates a highly aggressive form of triple-negative breast cancer but also appears to control it.

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