Day: 09/10/2016

Concussions at Altitude: No Longer Worth Investigating?

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Can a single meta-analysis of three retrospective studies really close the case on a controversial topic? Two researchers believe they have done just that for the risk of concussion for athletes in contact sports at higher altitude.
Gerald Zavorsky, PhD, of Georgia State University in Atlanta, and James Smoliga, DVM, PhD, of High Point University in High Point, N.C., said their review provides conclusive evidence that playing football at a higher elevation isn’t protective against concussion — and that other researchers shouldn’t waste any more time on the question.

“We firmly believe epidemiologic data are already sufficient to indicate that this is an issue that should not be examined further,” they wrote in a research letter in JAMA Neurology.
They noted that any additional research “will simply divert resources from more clinically effective research aimed at identifying modifiable risk factors for concussion, developing scientifically sound technologies that improve athlete safety, and improving acute and long-term management of sport-related head injuries.”
The potential biological mechanism? If higher altitude increases cerebral blood flow, it may lead to a slight brain swelling that creates a tighter fit between the brain and the skull, which prevents the brain from sloshing around, and potentially reducing concussions.
But Zavorsky and Smoliga say that mechanism “is not scientifically sound.”
In their meta-analysis, they found similar ranges in concussion rates at sea level (0.07% to 0.45%) and at higher altitudes of about 650 ft and above (0.06% to 0.50%), leading to no difference in relative risk of concussion in a random effects model.

However, not everyone is convinced that these findings are the last word. Four concussion experts from the University of Florida in Gainesville — Steven DeKosky, MD, Russell Bauer, MD, Mike Jaffee, MD, and Breton Asken — reviewed the research letter, and said that while the statistics were solid, there were several issues that limit the conclusions that can be drawn.
Only three studies met their inclusion criteria, which is too small a number “to ‘close the book’ on any scientific question, the large number of hits [included] notwithstanding,” DeKosky said, speaking on behalf of the foursome, none of whom were involved in the meta-analysis.
And all three were retrospective studies, which carry several caveats that prevent researchers from drawing firm conclusions. In this case, for instance, that includes variables such as “differences in acclimatization to the altitude by the visiting team and if it had an effect, and effects on autoregulation that might be different in low-altitude versus high-altitude players,” DeKosky said.
“The idea that three retrospective studies answers all the questions to the point where there is not more work to be done is, I think, a risky conclusion to an otherwise methodologically well-performed study,” he told MedPage Today. “Prospective studies, especially noting differences in the high-altitude acclimated versus the low-altitude dwelling visiting team, would be helpful in trying to determine actual risks.”

Novel Antibodies Homing in on New Targets for AML, MDS

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Patients with acute myeloid leukemia (AML) who have long-term disease-free survival following an allogeneic stem cell transplant (allo-SCT) may benefit from a robust immune response involving cytotoxic antibodies directed to a previously unsuspected cellular target, investigators from the Netherlands report.

The presence of these and other antibodies to newly identified cellular targets suggests new therapeutic strategies for treatment of AML and, potentially, for myelodysplastic syndromes (MDS), according to Mette D. Hazenberg, MD, PhD, from the Academic Medical Center in Amsterdam.

“What we learned from nature, from studying patients who through an allogeneic stem cell transplantation cured their leukemia, is that these patients make leukemia-specific antibodies to really unexpected targets,” she said in a report at the 2016 European Hematology Association (EHA) Congress in Copenhagen, Denmark.

By isolating and cloning anti-AML antibodies from long-term post-transplant survivors, Hazenberg and colleagues have identified antibodies that target small nuclear ribonucleoprotein U5 subunit 200 (U5 snRNP200). This large (250 kilodalton) protein is one of five major components of the spliceosome complex normally found within the nucleus of human and other eukaryotic cells, but which, as the team discovered, appears to be expressed on the cellular membrane of AML.

Long-term Survivors

“It has been shown that allogeneic stem cell transplants can mount immune responses, and we wondered whether antibodies could be involved in this,” Hazenberg said.

She and her colleagues selected three patients with high-risk leukemia who were alive for at least 5 years with no evidence of disease following an allo-SCT, whose longevity indicated a strong graft-versus-leukemia response. The investigators identified and isolated antibody-generating memory B cells from peripheral blood and cultured them in medium, screening the supernatant of the cultures and searching for antibodies that bind to AML.

The team then cloned the AML-binding B cells and identified 17 candidate monoclonal antibodies that bind to AML in cell lines, but do not bind to peripheral blood monocytes, fibroblasts, or other healthy cells. Of the 17 antibodies, seven recognized the same target: U5 snRNP200.

“We screened a few more patients, and found that four out of five patients had mounted such antibodies, so apparently that is a target that is often recognized by the immune system of the donor,” Hazenberg said. “The second striking observation was that these antibodies, when they interact with this protein on the cell membrane, actually kill the leukemic cells.”

Non-Apoptotic Process

The direct killing effect was seen both in AML cells in vitro, and in a human AML mouse model in vivo. The cell death occurred despite the absence of either cytotoxic leukocytes or of complement. Instead, the antibodies appear to induce AML death through a non-apoptotic process that relies on destabilization of the cytoskeleton. The nature of the cell death mechanism was supported by further experiments showing that AML cell death could be blocked when target cells were treated with cytochalasin D, an inhibitor of actin polymerization.

Furthermore, observation that the anti-U5 snRNP200 antibodies retained their cytotoxic abilities at both 4° and 37° C suggests that the cell death is induced through a passive process. This observation was further supported by the fact that the interaction of the antibodies with their target cells did induce calcium flux, the investigators noted.

 “Now with immunotherapy these days, investigators decide which target should be attacked by the immune system, and we try to help the immune system by making antibody drug conjugates, for example, but here we let nature decide what the target would be, and the target was, amongst others, this 200 subunit complex,” Hazenberg explained.

“And interestingly, when these antibodies bind to this complex they actually kill the target cell; they kill the leukemic cells. This is a novel phenomenon — we didn’t know this before — and we think we can develop this further into novel therapies.”

In a separate presentation at the EHA meeting, Hazenberg and colleagues reported on a second, novel tumor-specific target expressed on both AML and MDS blasts. The team first identified an immunoglobulin G1 antibody, labeled AT14-013, from the memory B lymphocytes of a patient with a robust graft-versus-leukemia response. This antibody homed in on a sialylated epitope of CD43 that is both uniquely and widely expressed on all types of AML.

Hazenberg and colleagues assert that antibodies targeted against onco-sialylated CD43 and U5 snRNP200 have significant potential as novel therapies for AML and MDS, either as “naked” antibodies or in combination in an antibody-drug conjugate, bispecific T-cell engager, or chimeric antigen receptor T cell (CAR-T) construct.

Why The Law Forbids The Medicinal Use of Natural Substances

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Why The Law Forbids The Medicinal Use of Natural Substances

According to the FDA’s legal definition, a drug is anything that “diagnoses, cures, mitigates, treats, or prevents a disease.”

The problem with this definition is that there are numerous substances, as readily available and benign as found on our spice racks, which have been proven by countless millennia of human experience to mitigate, prevent and in some cases cure disease, and which cannot be called drugs according to the FDA.

How can this be? Well, the FDA has assumed for itself Godlike power, requiring that its official approval be obtained before any substance can legally be used in the prevention and treatment of disease.

The FDA’s legal-regulatory control therefore is totalitarian and Napoleonic in construct; what it does not explicitly permit as a medicine is implicitly forbidden.

Historically the FDA has required new drugs undergo expensive and elaborate multi-phased clinical trials, which are out of the grasp of any ordinary interest who might want to demonstrate the efficacy of a non-patentable (and therefore unprofitable) herb, food or spice.

The average out-of-pocket cost for obtaining a new drug approval is US$ 802 million dollars,[1] and therefore an investor putting capital into bringing to market a substance that does not lend itself to market exclusivity and therefore cannot produce a return on investment, is committing economic suicide, if not also breaking the law. The investor actually has a legally-binding fiduciary responsibility to its shareholders to make a profit. And therefore, capital will not flow into any would-be commodity that can be produced or obtained with ease, including most things that grow freely on this Earth.

It is an interesting footnote in history that shortly after the Declaration of Independence, Congress declared that natural substances, e.g. water or salt, were God’s gift to mankind and that therefore products of nature should be limited in their patent protection. While this was a noble declaration, it has actually been used against those whose rights it would protect. It has forced private interests to synthetically alter natural substances — for instance the burgeoning biotech field of recombinant DNA technology, i.e. genetically modified organisms (GMOs) — for the sole reason that it guarantees them ownership/patent rights.

In fact, a medical system that legally requires it make a profit threatens to destroy and/or incriminate itself if non-patented, non-profitable natural substances or therapies are employed. It also results in so much collateral damage to those it purports to serve that it could rightly be called a modern form of human sacrifice.

As a result, instead of choosing prospective medicines logically: because they work, are easily accessible, and safe, billions of dollars flow in the exact opposite direction, capitalizing only those substances which are unnatural, and therefore while proprietary are almost invariably unsafe, and whose access and administration can be intensively controlled.

Has The Attempt To Co-opt Medicine Through the Drug-Based Model Undone Itself? 

And yet, there is a silver lining to the story. Due to the fact that our bodies are ultimately constructed from the natural things (food, air and water), and obey very strict natural laws such as the well-known principle of chirality (handedness) – the fact that all amino acids in our body turn a beam of polarized light in the left-handed direction (L-lysine) and sugars to the right-handed direction (D-ribose)– one cannot simply create biologically active, synthetic drugs arbitrarily, as a mistake in handedness (or similar property) could be fatal. Nature, therefore, still provides an elegant biomolecular architecture of irreproducible intelligence and complexity, from which synthetic analogs are modeled and/or derivatives are spun.

As a result, billions of dollars of drug industry and government money (i.e. tax payer money) flow into finding lead compounds for drug development.  Nature is put on the rack, if you will, and her secrets teased from her through innumerable animal and test tube experiments, in order to find compounds that can then be converted into synthetic, patented drugs.

Inadvertently, some of the very same companies and interests which require that natural substances not receive the same drug-approval status as synthetic ones, are funding research that prove basic vitamins, foods and spices are as effective or more effective – and usually much safer – than the drugs  they are developing to replace or supplant them.

This means that tens of thousands of studies do exist showing that natural substances may prevent and/or treat disease, at least in the in vitro (test tube) and animal models. These results often confirm traditional uses in Ayurvedic, Chinese and other traditional systems of medicine, and therefore may be compelling enough for individuals or healthcare practitioners to use the information to inform their treatment decisions.

The Case For Curcumin In the Prevention and Treatment of Disease

The government biomedical and life sciences database known as Medline contains over 21 million published study citations, and is accessible to search through engines such as Pubmed.gov.  2.6 million of them contain reference to cancer.  115,000 of them remain after applying the “Complementary Medicine” filter.   There are 2,625 topics on cancerwhich can be found indexed on the GreenMedInfo.com database, referencing 612 natural substances of potential value.

Turmeric, and particularly its polyphenolic constituent known as curcumin, which gives the spice its golden hue, is one of the most extensively studied natural compounds of all time, with 4588 references to it on the National Library of Medicine’s bibliographic database known as Medline [as of 2.25.2012]. And yet, despite having been shown to have therapeutic value in over 500 disease states in animal and in vitro studies, it still has not been the subject of extensive human clinical research – for the reasons stated above.

GreenMedInfo.com, an open source natural medicine database, has indexed curcumin’s anti-cancer properties in over 50 cancers, with the top 10 most cancers researched in association with curcumin listed below.

Cancer Number of Articles
Breast Cancer 58
Colorectal Cancer 23
Colon Cancer 51
Prostate Cancer 42
Pancreatic Cancer 24
Cancers: Drug Resistant 40
Lung Cancer 37
Liver Cancer 27
Cancer Metastasis 32
Skin Cancer 15

As one can see curcumin holds great promise. It has been repeatedly demonstrated to possess simultaneously both chemoprotective/chemosensitizing and radioprotective/radiosensitizing properties, meaning it is capable of reducing the adverse effects on healthy cells caused by chemotherapy and radiotherapy, as well as enhance the cancer-killing properties of these conventional therapies. It also has an exceptionally high margin of safety, at least an order of magnitude greater than commonly used conventional chemotherapy agents such as 5-fluoruracil.[2] Given these facts curcumin, at the very least, should be considered an ideal candidate for use as an adjuvant in integrative cancer care, and perhaps as a first-line treatment alternative to conventional chemo-agents.

For additional information on the remarkable research supporting the use of Turmeric and Curcumin in medicine, watch the video. URL:https://youtu.be/s2AZOMu0bVA

 

Becoming Human: Intel is Bringing the Power of Sight to Machines

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IN BRIEF

Intel acquires eight-year old startup Movidius to position itself as the leader in computer vision and depth-sensing technologies. While the details of the acquisition remain undisclosed, Intel and Movidius both stand to gain from this deal.

COMPUTER VISIONARY

No, this is not the beginning of a Terminator-esque world.

But yes, it certainly is a start of major developments in computer vision and machine learning technology. Intel is intent to boost its RealSense platform by acquiring Dublin-based computer vision startup Movidius.

With Intel’s existing framework, coupled with Movidius’ power-efficient system on chip (SoC), the pairing is bound to lead to major developments in consumer and enterprise products.

“As part of Intel, we’ll remain focused on this mission, but with the technology and resources to innovate faster and execute at scale. We will continue to operate with the same eagerness to invent and the same customer-focus attitude that we’re known for,” Movidius CEO Remi El-Ouazzane writes in a statement posted in their site.

TO ADD SIGHT TO MACHINES

With the existing applications of Intel’s RealSense platform, Movidius is even better equipped to realize its dream of giving sight to machines. But Movidius is not the only one that will benefit from this deal.

Movidius-Intel-drone-HZ-855x500
Remi El-Ouazzane and Josh Walden. Credit: Intel

“We see massive potential for Movidius to accelerate our initiatives in new and emerging technologies. The ability to track, navigate, map and recognize both scenes and objects using Movidius’ low power and high performance SoCs opens up opportunities in areas where heat, battery life and form factors are key,’ explains Josh Walden, Senior Vice President and General Manager of Intel’s New Technology Group.

Movidius has existing deals with Lenovo, for its Myriad 2 processors, and with Google, to use its neural computation engine to improve machine learning capabilities of mobile devices.

Breakthrough ‘Madala Boson’ Could Unlock the Mysteries of Dark Matter

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IN BRIEF

The Higgs’ boson helped us understand known matter, but scientists at the High Energy Physics Group (HEP) of the University of the Witwatersrand in Johannesburg believe they have the necessary data to discover a new boson, called the Madala boson. Its discovery may help us explore more about what dark matter is and how it interacts with the universe.

DISCOVERING THE MADALA BOSON

Discovery of the Higgs boson in 2012 at the European Organization for Nuclear Research (CERN) has contributed heaps to our understanding of modern physics. But the Higgs boson only explains mass that we can see, touch and smell. Known matter only makes up 4% of the Universe’s mass and energy. Scientists predict the discovery of a new boson which interacts with dark matter, which makes up 27% of our universe.

Using the same data that led to Higgs’ discovery, the bright minds at the High Energy Physics Group (HEP) of the University of the Witwatersrand in Johannesburg have come up with the Madala hypothesis, which they believe will help them discover the new Madala boson.

The Madala boson team isn’t lacking in scientific minds, as they have around 35 students and researchers to brainstorm and help understand data from the experiments. They also have the support from Wits University, such as theorists Prof. Alan Cornell and Dr. Mukesh Kumar and Prof. Elias Sideras-Haddad’s assistance in detector instrumentation.

Image credit: Taylor L; McCauley T/CERN

DARK MATTER MATTERS

Man’s understanding of physics keeps on evolving. Professor Bruce Mellado, team leader of the HEP group at Wits says we are now at a point similar to when Einstein formulated relativity and to when quantum mechanics came to light. We found classic physics lacking as it failed to make sense of plenty of phenomena. When the Higgs’ boson was discovered, the Standard Model of Physics was completed, but we have still only scratched the surface. Modern physics still can’t explain other phenomena including dark matter.

The discovery of the new Madala boson puts man in a good position to learn more about our universe. Perhaps there are even more particles to be discovered aside from this new boson. The future of modern physics has never been brighter.

New Lasers Made of Blood Could Revolutionize Cancer Detection

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Scientists from the University of Michigan have engineered a better way to track tumors with a laser that uses human blood.

LASERS — NOT THAT KIND BUT COOLER

Optofluidics, including the use of lasers, is not a new technology. Simply put, it is the application of some form of light to a liquid that serves as an amplifier, projected unto a reflective cavity. This technology is often used in medical research and surgery, like the use of infrared in scanning and imaging.

A group of researchers thought of a way to refine this technology, producing lasers with human blood.

It’s not exactly like the lasers in Star Wars, but it’s just as cool.

Human blood and an FDA-approved fluorescent dye called indocyanine green (ICG) made all the difference.  ICG has been used for decades now in imaging retinal blood vessels in ophthalmology. But without blood, “it doesn’t work at all,” says Xudong (Sherman) Fan, speaking to New Scientist. Fan is a professor in Biomedical Engineering at the University of Michigan.

BETTER TUMOR IMAGING

The researchers shone a form of infrared light on a reflective cylinder containing human blood with ICG as the amplifying material. The result was bright. The blood shone with the light, as ICG glows when mixed with protein in plasma.

Alfred Pasieka/SPL

With the light reflected back out, the researchers were able to observe cell structures and minuscule changes within the blood on a molecular level. The resulting fluorescence produced better imaging than current and existing techniques. Since ICG works well with blood, tissues that have a higher concentration of blood vessels — like tumors — will shine brighter.

Once the technology is refined to work on humans, this will be very useful in early cancer detection. “Eventually, we are trying to do it in the human body,” says Fan, but they are ensuring that the laser output is lower than recommended safety limits. “You don’t want to burn the tissue.”

Acid-Blocking Drugs Increase Heart Disease Risk

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Put down the antacids! New study shows that acid blockers are detrimental to cardiovascular health.

Proton-pump inhibitors (PPIs) are a group of drugs whose main action is blocking the secretion of gastric acid. They are dominant medical treatment of peptic ulcers, gastroesophageal reflux disease (GERD), and indigestion. Popular examples include Nexium, Prilosec, Protonix, Prevacid, and Aciphex. Use of these powerful antacids is associated with an increased risk for osteoporosis, heart arrhythmias, intestinal infections, bacterial pneumonia, and multiple nutrient deficiencies. A new study from Stanford University adds another issue with these drugs – they double the risk of dying from a heart attack or stroke.

PPIs will typically raise the gastric pH above the normal range of 3.5, effectively inhibiting the action of pepsin – an enzyme involved in protein digestion that can be irritating to the stomach. Although raising the pH can reduce symptoms, it also substantially blocks a normal body process. The manufacture and secretion of stomach acid is very important not only to the digestive process, but also because it is an important protective mechanism against infection. Stomach secretions can neutralize bacteria, viruses and molds before they can cause gastrointestinal infection.

As far as the digestive process, stomach acid is not only important in the initiation of protein digestion, it ionizes minerals and other nutrients for enhanced absorption; and without sufficient secretion of HCl in the stomach the pancreas does not get the signal to secrete its digestive enzymes.

PPIs drugs are associated with numerous side effects and here are just a small number of examples:

  • Pneumonia – People using acid blockers were 4.5 times as likely to develop pneumonia as were people who never used the drugs. Apparently, without acid in the stomach, bacteria from the intestine can migrate upstream to reach the throat and then lungs to cause infection.
  • Increased fractures – people taking high doses of acid-blocking drugs for longer than a year had a 260 percent increase in hip fracture rates compared to people not taking an acid blocker. Evidence suggests that these drugs may disrupt bone remodeling making bones weaker and more prone to fracture.
  • Vitamin B12 insufficiency – acid blocking drugs not only reduce the secretion of stomach acid, but also intrinsic factor (a compound that binds to and assists the absorption of vitamin B12). Vitamin B12 deficiency is among the most common nutritional inadequacy in older people. Studies indicate that 10 to 43 percent of the elderly are deficient in vitamin B12 making them at risk for a number of health conditions including dementia. Many elderly put away in nursing homes for Alzheimer’s disease, may simply be suffering from vitamin B12.

Stanford researchers examined over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk. Results from multiple data sources found use of PPIs to have a 16% increased risk for a heart attack and a two-fold increase in dying from heart disease compared to those not taking PPIs.

These results are consistent with pre-clinical findings that PPIs adversely impact the function of the endothelial cells that line blood vessels. Specifically, PPIs inhibit the enzyme required by the cells that line the vascular system that metabolizes a substance produced during metabolism known as asymmetric dimethylarginine (ADMA). If ADMA increases in vascular endothelial cells it inhibits the activity of the enzyme nitric oxide synthase. As a result it leads to an increase makes blood vessels more rigid as well as promotes inflammation and clot formation. PPIs increase ADMA levels in human vascular endothelial cells and in mice by about 20–30%.

The researchers stated “Our observation that PPI usage is associated with harm in the general population — including the young.” This statement is very significant given that that over 20 million people use prescription PPIs in the United States.

Five things you didn’t know about coffee

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While it may not be the most salubrious beverage around, it is definitely not the devil it is being made out to be.

The world is evenly divided into tea drinkers and coffee drinkers. While there are loads of people in both the camps – the java loyalists and tea addicts, between the two though tea is written about more, and also discussed much more, and usually in positive connotations. Coffee on the other hand, unfortunately seems to have become synonymous with caffeine and controversy – and is mostly derided as a health-messer, adding thus more than a tinge of guilt to its every sip. But the fact is that while it may not be the most salubrious beverage around, it is definitely not the devil it is being made out to be. It is time to chuck the guilt, or at least get the facts right about this muddy brew – and then make a choice.

beans-690_033015015203.jpg

It’s devoid of calories. Yes, coffee is actually an almost zero calorie cuppa (two calories in a cup) till we decide to make it anything but, by adding full fat milk, whipped cream, flavoured syrups, and of course, loads of sugar. Then it becomes the super-sized, frothy, sweetened beyond recognition liquid given complicated names that we sip stylishly in trendy cafes – and delivers humongous calories (sometimes more than a meal’s worth). So drink it as the Italians (and French) do – a small, black cup. And leave decadent coffees for special times only.

Research has shown clearly that the antioxidants in this bitter liquid are plenty, and three of these (caffeine, caffeic acid and chlorogenic acid) according to a study done by Chinese researchers, work together to keep the risk of type 2 diabetes down. Other scientists have put up other mechanisms that help stave off the risk of the disorder. Some say magnesium in it contributes, too… so even though it is not conclusively clear, the findings do indicate coffee having a beneficial role in helping to lower blood glucose levels. That’s definitely sweet news!

By the way, caffeine found in coffee is often used in headache relieving medications. But just like you wouldn’t want to pop too many pills, you would want to drink coffee in moderation too, as too much might just end up becoming a headache (besides causing other unwanted effects like rapid heartbeat, sleeplessness, brain fog, irritability). Besides, the jury is (still) out on whether caffeine cures or causes headaches… so, till there is a clear consensus, getting addicted surely seems like a bad idea.

Caffeine in coffee bumps up our dopamine levels and adenosine production; both are neurochemicals that help cut fatigue, boost our mood and liven us up. And let’s face it – there are times when we do need help in being revived from our zombie states. That said, the fact is that too much coffee (say, on the hour, like some people I know) does more harm than help; the caffeine in it gives us a temporary lift but a slump follows soon enough. Plus it is a diuretic and may dehydrate the body (the jury is out on this one too) and stress the energy reserves. So going easy on it is the logical advice here.

Research is now coming in about coffee’s benefits for the liver, too. A review has shown that the beverage helps prevent liver inflammation. Plus, some studies show that it helps boost memory, and keep Parkinson’s, Alzheimers and dementia away. Some scientists are pointing out its cancer prevention benefits, too. Too early to say anything conclusively about these, so the take away to date is that one can/must enjoy this rich multi-layered brew responsibly! Most experts peg one to three cups a day as sensible and safe, and a range that’ll maximise the benefits and hedge the risks.

The US has given fast-track approval to a surprising new cancer drug

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“Even when it’s killing cells, you feel great.”

A new cancer drug called Venetoclax is causing quite a stir in the medical community, with the announcement that the US FDA has given it fast-track approval for the treatment of patients with chronic lymphocytic leukemia (CLL).

CLL is one of the most common types of leukemia in adults, and during a recent clinical trial, 80 percent of patients treated with Venetoclax experienced complete or partial remission of their cancer.

Developed in Australia over several decades, Venetoclax is taken in pill-form, and of the small sample of patients who have been treated with it so far, some reported no adverse side-effects at all.

“It causes no side-effects. Nothing, absolutely nothing,” Robert Oblak, who had recurring CLL when he was selected to participate in the trial in 2013, told the ABC. “Quite amazing. So even when it’s killing cells, you feel great.”

Oblak estimates that he was just the 11th person in the world to be treated with Venetoclax, and within a year of treatment, he went into remission.

The phase II trial involved 107 patients aged 18 or older with CLL, who had undergone at least one type of treatment already.

The patients also had to have a particular chromosome abnormality in their leukemia cells called 17p deletion, which means they’re lacking a portion of the chromosome that acts to suppress cancer growth.

They were asked to take one Venetoclax pill per day for five weeks straight, with doses starting at 20 mg and gradually increasing to 400 mg.

At the end of the trial, which involved patients and researchers from 31 centres in the US, Canada, the UK, Germany, Poland, and Australia, four out of five patients experienced a positive result, with complete remission reported for one in five.

“These patients now have a new, targeted therapy that inhibits a protein involved in keeping tumour cells alive,” Richard Pazdur from the FDA’s Centre for Drug Evaluation and Research, announced back in April. 

“For certain patients with CLL who have not had favourable outcomes with other therapies, Venclexta may provide a new option for their specific condition.”

The results of the trial, which were published in The Lancet in June, informed the FDA’s decision to fast-track approval of the drug and make it available to patients in the US.

Despite being developed by researchers at Australia’s Walter and Eliza Hall Institute of Medical Research, it’s not yet been approved for use by Australian patients, but an application has been made.

So, how does the drug work? Venetoclax is one of a new generation of immunotherapy cancer drugs that are designed to address certain failings of a person’s own immune system – such as missing portions of chromosomes that inhibit the cells’ ability to fight the spread of cancer.

In CLL patients with 17p deletion, malignant cells don’t proliferate all that much, but they don’t die, because the body’s immune response has been hindered, and abundant levels of a protein called BCL2 helps keep them alive.

“Cells, when they are born, are destined to die and cancer cells and particularly leukaemia cells delay that death by using a protein called BCL2 that stops the normal time of death,” John Seymour from the Peter MacCallum Cancer Centre in Melbourne, who helped oversee the trial, told the ABC.

“Venetoclax works by specifically blocking the action of that BCL2, and allows the cells to die in the way that they were destined to.”

venetoclax-actionVenetoclax

So rather than killing off the cancer cells – and a bunch of healthy cells in the vicinity – like current treatments like chemo and radiotherapy do, the drug reestablishes the balance of the body’s immune system, and effectively allows the cancer cells to die on their own.

This explains why some patients, like Oblak can undergo treatment with no discernible side-effects. But let’s be clear – Oblak was very lucky.

The FDA reports that, depending on the patient, side-effects from Venetoclax include low white blood cell count, diarrhoea, nausea, anaemia, upper respiratory tract infection, low platelet count, and fatigue. Serious complications can include pneumonia, fever, and death.

During the Venetoclax trial, of the 107 patients, 11 ended up dying, seven because of the progression of their cancer, and four from adverse side-effects.

Similar results were seen in a separate trial of a similar immunotherapy cancer drug, Ipilimumab, which has recently been approved for the Australian market.

While Australian patient Greg Lawson was declared free from melanomas 12 months after treatment, and reportedly suffered “virtually no side-effects”, his wife, who was treated with a different melanoma immunotherapy drug at the same time, died when her body could not tolerate the treatment.

“She had two sets of the treatment, but was so ill from the side-effects that the decision was made to take her off it,” Lawson told the ABC.

But with immunotherapy drugs seeing “extraordinary” results in other trials this year, and with the possibility of a ‘universal cancer vaccine’ hanging in the air, this is just the beginning for the next generation of cancer treatment.

 

Babies born by caesarean section are more likely to be obese, study finds

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Obesity is a lot more complex than we think.

Babies born by caesarean section are more likely to experience obesity than children delivered via vaginal birth, a new study has found.

The study suggests that babies from caesarean deliveries don’t only experience greater incidence of obesity as children, but also later on in life – with the effects persisting through teenage years and into adulthood.

“Caesarean deliveries are without a doubt a necessary and lifesaving procedure in many cases,” says nutritionist and epidemiologist Jorge Chavarro from Harvard University.

“But cesareans also have some known risks to the mother and the newborn. Our findings show that risk of obesity in the offspring could another factor to consider.”

The researchers analysed data from more than 22,000 young adults who took part in the Growing Up Today Study (GUTS) – an ongoing project launched in 1996 to examine the factors that influence health and weight as people age.

The participants, who were children aged between 9 to 14 when the study commenced, had their body mass index (BMI) tracked over 16 years. The researchers also collected information on factors that might affect obesity, including their mothers’ pre-pregnancy BMI, smoking status, and age when the participants were born.

Once these factors were accounted for, the data showed that participants born via caesarean deliveries (22 percent of the group) were 15 percent more likely to be obese on average than those who came into the world via vaginal birth (the other 78 percent).

The association showed up in across genders and different age segments, but was at its strongest when the participants were younger.

Participants born via C-section were 23 percent more likely to be obese when aged 9–12; 16 percent more likely to be obese when aged 13 to 18; and 10 percent more likely when aged 19 to 28.

Strangely, the increased risk of obesity was at its highest when pregnant women had elected to have caesarian births without a documented health reason for the C-section, with their babies found to be 30 percent more likely to experience obesity than children delivered via vaginal birth.

Also of note is the fact that participants in the study with siblings – 12,903 of the overall 22,068 group – who were delivered by caesarian had a 64 percent higher risk of obesity than their brothers or sisters from a vaginal birth.

While researchers have previously observed this association between caesarean sections and obesity, this is the largest and most comprehensive investigation yet into the relationship between birthing methods and future weight outcomes.

“I think that our findings – particularly those that show a dramatic difference in obesity risk between those born via caesarean and their siblings born through vaginal delivery – provide very compelling evidence that the association between caesarean birth and childhood obesity is real,” says Chavarro.

“That’s because, in the case of siblings, many of the factors that could potentially be playing a role in obesity risk, including genetics, would be largely the same for each sibling – except for the type of delivery.”

But the question remains, why is this happening?

At this stage, nobody knows for sure, but children born by caesarian section do have less exposure to their mother’s vaginal and gastrointestinal microbiota, and this could play a role in their dietary development and weight as they age.

“Children born via C-section harbour less diverse gut bacteria and these patterns of less diversity have been linked to increased capacity for energy harvest by the gut microbiota,” one of the researchers, Audrey Gaskins, told Hannah Devlin at The Guardian. “You can think of it as a slower metabolism.”

It’s important to remember that, for many women, giving birth via a C-section is a medical necessity to safeguard the health of the mother and her baby – so the researchers are not suggesting that women avoid using this method in a bid to lower their child’s risk of developing obesity.

A definitive biological cause is yet to be identified to explain this correlation, so until the link can be confirmed, we need to wait and see what further evidence reveals. But one thing’s for sure – getting to the bottom of what’s really going on here will be beneficial for all.

“Most often caesarean births are as a result of medical necessity, rather than elective,” biomedical researcher Simon Cork from Imperial College London in the UK, who wasn’t involved with the study, told The Guardian. “[A]s such, this risk would outweigh any concerns mothers should have regarding the possibility of future weight issues.”