Day: May 18, 2022

Radio DJ Mark Pilgrim Shares Good News on His Cancer Treatment

Radio DJ Mark Pilgrim has revealed on Twitter that his latest scan results showed a ‘significant shrinkage’ of all of the tumours present in his lung, spine, leg and lymph nodes.

In March 2022, the radio star revealed that he had been diagnosed with stage 4 lung cancer, and that he was to start treatment “in a week”.

Speaking about his most recent diagnosis, he said: “I’m not Chuck Norris. Yes, I’m scared. I am also strong. Both emotions run parallel with each other. I’m under the care of incredible doctors and surrounded by love.”

It is not the first time the popular DJ has been through such difficult times. Pilgrim had already survived stage stage 4 testicular cancer in 1998 at the age of 18. The cancer had spread to his lungs and kidney, and he recalls that his oncologist said that his prognosis was “uncertain”. He endured 9 months of 4-hour chemotherapy sessions.

In 2008 he suffered heart damage from a massive myocardial infarction suffered in the doctor’s office, and last year he tested positive for COVID.

For patients with non-small cell lung cancer (NSLC), the most common form of lung cancer, half present at stage 4. In one Canadian study, only 14.9% of patients received chemotherapy as first-line treatment, with most patients receiving palliative radiotherapy.

A Tangled Web of Brain Damage from Concussions in Children

Boy hanging from tree
Photo by Annie Spratt on Pexels

Concussion may cause different types of brain damage which lead to similar symptoms in children, according to research published in eLife. A new way of studying concussions could help inform the development of future treatments.

While most children fully recover after a concussion, some will have lasting symptoms. The findings help explain the complex relationships that exist between symptoms and the damage caused by the injury.

The researchers found that certain combinations of brain damage were associated with specific symptoms such as attention difficulties. Other symptoms, such as sleep problems, occurred in children with multiple types of injuries. For example, damage to areas of the brain that are essential for controlling sleep and wakefulness could cause challenges with sleeping, as could damage to brain regions that control mood.

The brain’s white matter holds clues

To do this, they examined how damage to the brain resulting from concussion affected its structural connection network, known as white matter. They then used statistical modelling techniques to see how these changes related to 19 different symptoms reported by the children or their caregivers.

Analysing symptoms may advance treatment

“Despite decades of research, no new treatment targets and therapies for concussions have been identified in recent years,” said lead author Guido Guberman, a Vanier Scholar and MDCM Candidate at McGill University. “This is likely because damage to the brain caused by concussions, and the symptoms that result from it, can vary widely across individuals. In our study, we wanted to explore the relationships that exist between the symptoms of concussion and the nature of the injury in more detail.”

Guberman and his colleagues analysed data collected from 306 children, aged nine to 10 years old, who had previously had a concussion. The children were all participants in the Adolescent Brain Cognitive Development (ABCD) Study.

“The methods used in our study provide a novel way of conceptualising and studying concussions,” says senior author Maxime Descoteaux, a Professor of Computer Science at Université de Sherbrooke. “Once our results are validated and better understood, they could be used to explore potential new treatment targets for individual patients. More broadly, it would be interesting to see if our methods could also be used to gather new insights on neurological diseases that likewise cause varied symptoms among patients.”

Source: McGill University

Over-the-counter Drugs and Supplements Overlooked in Polypharmacy

Pills and tablets
Photo by Myriam Zilles on Unsplash

While patients usually report any medications they are on, over-the-counter drugs and supplements are not reported as often to the medical team, according to a study on polypharmacy published in The Oncologist, an overlooked situation that complicates the problem of polypharmacy, especially in cancer.

Polypharmacy can lead to harmful drug interactions, especially dangerous for cancer patients about to undergo therapy.

Even for those without cancer, multiple medication use has risks and is tricky to navigate because of the emotions involved, said Erika Ramsdale, MD, study leader.

“As doctors, we tell people to take medications but we don’t always do a great job of following up,” she said. “From the patient perspective, if it’s determined that a medication is no longer needed, it’s hard to stop taking it. There’s a sense of, ‘What will happen if I stop?’ or ‘Are you giving up on me?’ A lot of uncertainty and emotions are tied up in this issue.”

The more drugs and supplements a person takes, the higher the risk of inappropriate use and serious drug interactions, she said.

The fragmentation of healthcare across specialties complicates the issue. “Sometimes, there is no quarterback,” Dr Ramsdale said, which can result in “prescribing cascades,” where additional drugs are given to offset the adverse side effects of the original medications.

Researchers analysed medication use in a sample of 718 adults with a mean age of 77 who had stage 3 or 4 cancer and other health conditions. They screened for potentially inappropriate medications that have risks higher than benefits (known as PIMS), drug-drug interactions (DDI), and drug-cancer treatment interactions (DCI). Drug interaction can have consequences such as falls, functional decline, and death. Patients on multiple medications are also more likely to have anxiety or depression.

Among the 718 patients, 70% were at risk of drug-drug interactions and 67% were taking at least one drug that was potentially inappropriate.

In fact, 61% of the patients were taking five or more medications before starting chemotherapy – and nearly 15% were taking 10 or more medications.

Other findings from the study include:

  • Nearly 68% of the patients had serious health issues besides cancer, requiring associated medications. Most common was cardiovascular disease. When a person has cancer combined with other ailments, there is a greater risk of toxicity from cancer treatments due to polypharmacy.
  • Approximately 10% of hospital admissions for older adults are associated with hazardous drug interactions. Among older adults with cancer receiving chemotherapy, polypharmacy is associated with dramatic increases (up to 114%) in unplanned hospitalisations.
  • Cholesterol-lowering medications, minerals, and thyroid therapy are most commonly involved in potential drug interactions.
  • More than 25% of the medications used by the patients in the study were non-prescription—and these accounted for 40% of the potentially inappropriate medications detected by investigators.
  • Common non-prescription remedies included vitamins and minerals, anti-anemic preparations such as ferrous sulfate, and drugs for acid-related disorders and constipation.

“Older adults may incorrectly assume that over-the-counter medications are safe for them,” the authors wrote. “This study helps delineate the size and shape of a problem under-recognised by both providers and patients.”

It’s also an understudied problem, Dr Ramsdale said, and including over-the-counter medications sets Wilmot’s data apart from previous research; most polypharmacy studies among cancer patients look only at prescription drugs.

The study highlights an opportunity for education and problem-solving, such as deprescribing some drugs.

Deprescribing is the planned reduction of medications to avoid harm. Doctors take into account the risks-versus-benefits of each medication and the patient’s life expectancy. For example, statins that are taken for high cholesterol do not have an immediate effect. They are meant to be preventive and can take 10 years to have an impact. Therefore, if a patient is old and has incurable cancer, he or she may not need to take statins. (Discontinuing statins in this setting is supported by a landmark study, according to the Ramsdale publication.)

However, these conversations can be quite delicate, Ramsdale said. The goal is to promote better quality of life, and she is conducting a clinical trial to test the best way to intervene in cases of polypharmacy among older people with cancer.

Source: University of Rochester Medical Center

High-fat Diets Increase Nitric Oxide, a Cancer Promoter

A hamburger
Photo by Ilya Mashkov on Unsplash

Research which appears in ACS Central Science has shown that a direct link exists between the amount of fat in the diet and bodily levels of nitric oxide, a naturally occurring signalling molecule that is related to inflammation and cancer development.

Nitric oxide (NO) is one of the critical components of the vasculature, regulating key signalling pathways in health. In macrovessels, NO functions to suppress cell inflammation as well as adhesion. In this way, it inhibits thrombosis and promotes blood flow. It also functions to limit vessel constriction and vessel wall remodelling. In microvessels and particularly capillaries, NO, along with growth factors, is important in promoting new vessel formation, a process termed angiogenesis. With age and cardiovascular disease, animal and human studies confirm that NO is dysregulated at multiple levels including decreased production, decreased tissue half-life, and decreased potency.

“We are trying to understand how subtle changes in the tumour microenvironment affect cancer progression at the molecular level. Cancer is a very complicated disease,” said Anuj Yadav, a senior research associate and the study’s lead coauthor.

Cancer is more than just a few tumour cells, rather the entire microenvironment of the tumour supporting the cells, Yadav explained.

“Inflammation can play a significant role in this environment. Certain inflammatory response comes from highly processed foods, which are high in calories and high in fat. We wanted to understand the links between food, inflammation, and tumors at a molecular level, so we had to develop advanced probes to be able to visualise these changes,” he said.

Yadav and coauthors are familiar with existing research linking increased NO levels to inflammation, and inflammation to cancer. Proving the connection between high-fat diets and NO levels on a molecular level required developing a highly sensitive molecular probe capable of deep-tissue imaging.

The team designed a molecular probe which is the first of its kind to be used in bioluminescence imaging of NO in cancer.

“Our group specialises in making designer molecules, which allows us to look at molecular features that are invisible to the naked eye,” said Jefferson Chan, an associate professor of chemistry at the University of Illinois Urbana-Champaign and the study’s principal investigator. “We design these custom-made molecules to discover things that weren’t previously known.”

With the probe, the researchers compared the tumourigenicity of the breast-cancer-carrying mice on a high-fat diet (60% of calories coming from fat) with mice on a low-fat diet (10% of calories coming from fat) by measuring the NO levels in both groups.

“As a result of the high-fat diet, we saw an increase in nitric oxide in the tumor microenvironment,” said Michael Lee, a student researcher in the Chan lab and a lead coauthor on this study. “The implication of this is that the tumor microenvironment is a very complex system, and we really need to understand it to understand how cancer progression works. A lot of factors can go into this from diet to exercise – external factors that we don’t really take into account that we should when we consider cancer treatments.”

The authors emphasised the importance of proving a direct link between a high-fat diet, NO levels, and cancer development. With this association now known, new implications exist for cancer diagnosis and treatment.

“Without this technology, you wouldn’t see this missing molecular link,” said Chan. “Now that we know that this is happening, how do we prevent it, and how do we improve the situation?”

Source: Beckman Institute

Methylprednisolone Halves Kidney Failure Risk in IgA Nephropathy

Anatomic model of a kidney
Photo by Robina Weermeijer on Unsplash

A large study has found that treatment with methylprednisolone – a cheap, widely used corticosteroid – halves the risk of losing kidney function and kidney failure in IgA nephropathy. The study, published in the journal JAMA, also found that this can be effectively achieved with fewer side effects if a reduced dose is used.

Researchers say the results of the multi-country study will provide a clear treatment option with definite benefits outweighing well defined and mostly manageable risks. 

IgA nephropathy is a common form of glomerulonephritis caused by the deposition of IgA immunoglobulins in the glomerular basement membrane. Immune-mediated damage to the basement membrane results in haematuria and renal insufficiency progressing to kidney failure in some.

Joint Principal Investigator Professor Vlado Perkovic said that around 10–30% of people with the condition go on to develop kidney failure that requires dialysis or kidney transplantation to prevent death.

“There are few proven treatment options so many treatments including corticosteroids have been used in some patients for decades, despite uncertainty about their effectiveness, as well as the ideal dose. This has led to significant regional variability and clinical uncertainty about this treatment,” he said.

The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study is a double-blinded, randomised, controlled trial that assessed the effects of oral methylprednisolone on major kidney outcomes, kidney failure and safety in patients with IgA nephropathy.

503 patients diagnosed with IgA nephropathy were recruited from centres across Australia, Canada, China (including Hong Kong), India and Malaysia between May 2012 and November 2019. Patients were randomised to receive methylprednisolone or a placebo at:

  1. full dose of 0.6-0.8mg/kg per day of methylprednisolone or placebo for 2 months reducing by 8mg per day each month (262 participants between May 2012 and November 2015), or
  2. reduced dose of 0.4mg/kg per day of methylprednisolone or placebo, also for two months, reducing to 4mg per day each month (241 participants between March 2017 and November 2019), 

for a total treatment period of 6–9 months.

“We found that that treatment with methylprednisolone for six to nine months significantly reduced the risk of losing substantial kidney function, kidney failure requiring dialysis or transplantation, or death from kidney disease compared to placebo,” said Professor Perkovic.

“However, there was an increase in serious adverse events in those who received methylprednisolone, mainly seen in the full dose regimen with fewer in the reduced dose treatment group.”

Joint Principal Investigator Professor Hong Zhang said that with IgA nephropathy being an immune-mediated condition, the benefits seen were likely due to the immune suppressing action of the steroid treatment.

“A well-known side effect of steroid treatment is an increased risk of infections, but we found that this could be mitigated to a degree by using the lower dose and giving the patients antibiotics to prevent infections,” she said. 

“This is the strongest evidence yet for the benefit of any treatment for the prevention of kidney failure in people with IgA nephropathy.

“The results provide a treatment option for clinicians and patients, especially at the lower dose, given the net benefits versus the risk of side effects,” she added.

Associate Professor Muh Geot Wong said that given that the condition develops slowly, and that there was some indication that the effects of treatment appeared to diminish over time, the research team have now extended the study.

“We are now following a significant number of patients from our original study for another five years so we will have a total of around ten years follow up,” he said.

“By then, we hope to have the most comprehensive set of evidence ever collected to help guide the treatment of people with this type of kidney disease.”

Source: EurekAlert!

Early Warning Signs for Age-related Macular Degeneration

Credit: National Eye Institute

In an important step in treating a major cause of blindness, scientists have successfully identified early signs of age-related macular degeneration (AMD), in which higher number of mast cells are observed. This finding could be exploited by new treatments before symptoms develop. The study is published in PNAS.

Scientists have long known that people with certain genes on chromosomes 1 and 10 have a 2- to 3-fold higher risk of developing AMD, although lifestyle factors also play a role.

The team identified higher numbers of mast cells in the eyes of people when either of the risk genes were present, even when there were symptoms, suggesting an early mechanism in common.

They also showed the mast cells release enzymes in the back of the eye which then damage structures underneath the retina that in time is likely to damage the retina itself.

Mast cells exist in most tissues and are one of the immune system’s first defenses against infection, especially parasitic disease and damage.

Scientists already know there are more mast cells in the choroid in people with established AMD. The current study, however, identified higher levels in people before the disease develops.

The genes on chromosome 1 are linked to a part of the immune system called the complement cascade, which is associated with a risk of AMD.

Though the functional role of genes expressed by chromosome 10 are not known, but increased risk of AMD is.

Dr Richard Unwin, one of the study leaders, said: “What is really exciting about this work is that we are studying tissue from people before they have signs of the disease. This gives us a look into the very earliest stages, and gives us hope that we can intervene to stop the disease developing and ultimately prevent loss of vision”

The scientists used healthy human eye tissue donated post mortem to the Manchester Eye Tissue Repository.

They identified those who are at risk of developing age-related macular degeneration based on their risk genes, and discovered underlying changes in the tissue of the otherwise healthy at-risk individuals.

They collected retinal tissue from the back of donor eyes post mortem, following removal of the cornea for transplantation.

Then they took a small sample from the macula and removed the cells to leave a thin layer of membrane which supports the photoreceptors called rod and cone cells and is where disease begins.

They analysed the proteins present in the membrane from 30 people using mass spectrometry, which identifies protein components based on their mass, to find differences in the tissue make-up between those with and without genetic risk of AMD.

The mass spectrometry, identified a series of enzymes which are made almost exclusively by mast cells. In tissue from an additional 53 people, higher levels of mast cells were found in patients with higher disease risk.

Dr Unwin added: “We next need to look at how mast cells are activated, and whether by preventing, or clearing mast cell activation we can slow or stop disease development. There are several researchers and companies looking at complement mediated-therapies for AMD and while these are promising for Chr1-related disease there is no evidence that they will have an effect on Chr10 disease. A therapy designed to target mast cell activation as a unified mechanism could in theory treat all patients with AMD and prevent sight loss.”

Source: University of Manchester