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Kids prescribed antibiotics but not fed breast milk at triple risk of asthma: study

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A Canadian study suggests children who were not breastfed while receiving antibiotics in the first year of life had triple the risk of developing asthma because they lacked specific protective sugars found in human milk.

Dr. Stuart Turvey, a lead researcher, said antibiotics such as amoxicillin are commonly prescribed to treat a wide range of infections in young children, but the medications have also been linked with disrupting the development of a healthy gut microbiome.

“What we’ve known for some time was that babies that got antibiotics early in life were at higher risk of having asthma at school age and beyond but no one knew why,” said Turvey, a pediatrician at BC Children’s Hospital.

The study, published Wednesday in the journal Med, found that sugars in breast milk, which make up about 20 per cent of its indigestible carbohydrates, promote the growth of the B. infantis bacteria to help make other bacteria in order to train the immune system and prevent the development of asthma and allergies.

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Researchers also said they identified the breast milk sugars that offer this protection, which could potentially be used to supplement formula for infants that need antibiotics but for whom breastfeeding is not an option.

“Children are born with pretty much no bacteria,” Turvey said. “Then these communities (of bacteria) start to build, with pioneer species that help the other ones colonize. So the timing matters,” he said of when people are prescribed antibiotics, which “confuse” kids’ immune systems in the first few months of their lives.

The research involved a total of 2,521 children in Vancouver, Edmonton, Winnipeg and Toronto. It showed 17 per cent of the kids received antibiotics in the first year of life.

Three groups of kids were compared — those who received no antibiotics, those who were given them while being breastfed and those who got them without being breastfed.

When a subset of 1,338 children were three months old, researchers collected a dirty diaper to test the stool. A year later, another diaper was collected for a stool sample from the same kids, said Turvey, adding the expense of the relatively new technology prohibited all of the children’s samples from being tested.

“We got the poop samples and then we did metagenomics, a type of genetic sequencing, to identify all the bacteria by the DNA that’s there. This (B. infantis) came up as a really strong signal,” he said.

At age five, all the children were assessed for asthma. Those who did notreceive breast milk but had been prescribed antibiotics were at three times the risk of having the condition.

“The children who received the antibiotics while breastfeeding weren’t at any higher risk than the children whodid not have antibiotics,” Turvey said.

“One important thing was that any breastfeeding was protective. So it wasn’t just exclusive breastfeeding, with no other form of nutrition.”

Asthma is a top reason for kids visiting for emergency rooms and doctors’ offices, often while missing school, he said, adding that despite the findings, amoxicillin is a potentially life-saving drug for very young kids.

The study findings could spur clinical trials to determine if the natural sugars in breast milk can be used to supplement formula for the benefit of people who can’t breastfeed their children, Turvey said. Chemists could make synthetic versions of the sugars, similar to some that are already in formula, he added.

“More knowledge about the protective ones could inform that process.”

Ailbhe Smyth, a volunteer with a Vancouver chapter of La Leche League, which supports breastfeeding mothers, said those who are struggling with what is often a challenging experience, as it was for her, should not take the findings as another reason to feel guilty about being “a perfect parent.”

Fewer public health clinics were offering support through lactation specialists even before the pandemic and some women are opting for private consultants to avoid long wait lists, Smyth said.

“But that’s still a barrier. Some people just don’t have the extra money to do that,” she said, adding: “I think support doesn’t only need to come from the health-care system because it has to come from society in general.”

—Camille Bains, The Canadian Press

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GLP-1 Agonists Protected Kidneys in T2D With Advanced DKD – Medscape

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Researchers published the study covered in this summary on Research Square as a preprint that has not yet been peer reviewed.

Key Takeaways

  • In patients with advanced diabetic kidney disease (DKD; estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73m2), treatment with a glucagon-like peptide-1 (GLP-1) agonist had a neutral effect on cardiovascular outcomes but significantly linked with preservation of kidney function and improved survival in a propensity-score matched, retrospective analysis of observational data from more than 2000 people with type 2 diabetes in Taiwan.

Why This Matters

  • Cardiovascular disease is a leading cause of mortality in people with type 2 diabetes and among those with chronic kidney disease.

  • GLP-1 agonists reduce all-cause mortality and cardiovascular death in people with type 2 diabetes, but their role in patients with advanced DKD is controversial.

  • Research on the effect of GLP-1 agonists on cardiovascular outcomes in patients with advanced DKD is limited. Trials that have assessed GLP-1 agonists in people with type 2 diabetes have generally excluded those with advanced DKD and completely excluded those with end-stage kidney disease (eGFR < 30 mL/min/1.73m2).

  • Treatment with GLP-1 agonists has been associated with a significant reduction in composite cardiovascular outcomes in people with type 2 diabetes and relatively fair kidney function (eGFR > 30 mL/min/1.73m2), but among people with type 2 diabetes and lower levels of kidney function, research has shown neutral composite cardiovascular outcomes levels. However, limitations of previous studies include being mainly based on subgroup analysis or including a limited sample of patients.

Study Design

  • Retrospective analysis of observational data from nearly 9000 people in Taiwan with type 2 diabetes and an eGFR < 30 mL/min/1.73m2 who received a first prescription for a GLP-1 agonist or dipeptidyl peptidase 4 (DPP-4) inhibitor in 2012-2021 and had the data necessary for this analysis in their records.

  • The data came from the largest multi-institutional electronic medical record database in Taiwan, which includes two medical centers and five general hospitals and information on more than 11 million patients, from 2001 to 2019.

  • Researchers used propensity scoring to match 602 people treated with a GLP-1 agonist with 1479 people treated with a DPP-4 inhibitor.

Key Results

  • During a mean follow-up of 2.1 years, the rate of the composite cardiovascular outcome (cardiovascular death, myocardial infarction, and ischemic stroke) did not significantly differ between the GLP-1 agonist and DPP-4 inhibitor groups, with incidence rates of 13.0% and 13.8%, respectively, and a nonsignificant hazard ratio of 0.88. Rates of each of the three components of the composite endpoint also did not significantly differ between the two groups.

  • Progression to end-stage kidney disease with dialysis was significantly lower in those treated with a GLP-1 agonist compared with a DPP-4 inhibitor, with incidence rates of 23.4% and 27.5%, respectively, and a significant hazard ratio of 0.72.

  • The incidence of a greater than 50% drop in eGFR from baseline was 32.2% with GLP-1 agonist treatment compared to 35.9% with a DPP-4 inhibitor, with a significant hazard ratio of 0.74.

  • Median time until patients needed new-onset dialysis was 1.9 years with GLP-1 agonist treatment and 1.3 years with DPP-4 inhibitor treatment, which was a significant difference.

  • The rate of all-cause death was 18.4% with GLP-1 agonist treatment compared with 25.1% with DPP-4 inhibitor treatment, a hazard ratio of 0.71 that was significant.  

Limitations

  • Because the study was a retrospective analysis of observational data it cannot prove causality.

  • The study could be subject to residual confounding despite propensity-score matching.

  • The data came from health records that could have included coding errors.

  • Treatment compliance was unknown.

Disclosures

This is a summary of a preprint research study, “The cardiovascular and renal effects of glucagon-like peptide 1 receptor agonists in patients with advanced diabetic kidney disease,” by researchers in Taiwan on Research Square and provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on researchsquare.com.

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Research by UBC professor lays groundwork for life-saving breast cancer treatment – UBC Faculty of Medicine

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A drug originally designed to prevent osteoporosis is now expected to save and improve the lives of millions of people with breast cancer, thanks in part to decades of foundational research by Dr. Josef Penninger, a professor in UBC’s Faculty of Medicine and director of the Life Sciences Institute.

The achievement highlights how UBC scientists are developing effective new treatments — and unlocking the full potential of existing drugs – through research into the fundamental biological principles behind disease. By advancing scientific discoveries from the lab to the clinic, UBC researchers are bringing life-changing treatments to patients everywhere.

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The drug, called Denosumab, was recently shown in a long-term Phase 3 clinical trial to improve survival among postmenopausal women with hormone receptor-positive early breast cancer receiving aromatase inhibitor treatment. Moreover, the drug markedly improved patients’ quality of life by reducing broken bones by 50 per cent, a common side effect of breast cancer treatment. The results of the trial were recently reported in The New England Journal of Medicine.

Denosumab is a monoclonal antibody developed by American biopharmaceutical company Amgen to prevent bone loss. In the early 2000s, research by Dr. Penninger and his team revealed the therapeutic potential of Denosumab, as well as the drug’s surprising connections with breast cancer.

“More than two decades ago we started the experimental groundwork that revealed Donosumab’s potential as a treatment for breast cancer patients,” says Dr. Penninger. “These results are incredibly exciting and will help improve the lives of millions of patients. I am very proud of all the people in my lab over the years who did that work and helped pave the way for this achievement.”

Discovering the link between osteoporosis and breast cancer

Denosumab works by binding to and inhibiting the activity of a protein called RANKL, which plays a key role in bone-resorbing cells called osteoclasts. By blocking RANKL, denosumab reduces the activity of osteoclasts and slows down bone resorption, helping to increase bone density and preventing osteoporosis.

Dr. Josef Penninger

Dr. Josef Penninger

Dr. Penninger and his team began to draw the connection between osteoporosis and HR-positive breast cancer when they generated the first RANKL “knock-out” mice in the late 1990s.

A knockout mouse is a laboratory mouse that has been genetically engineered to have certain genes deactivated, or “knocked-out”. Dr. Penninger’s team engineered mice that lacked the genes necessary to produce the RANKL protein in an effort to study the protein’s essential function in bone metabolism.

However, to the researchers’ surprise, they discovered that the RANKL-deficient mice failed to develop a lactating mammary gland in pregnancy – a process that depends on sex hormones.

“This proved an evolutionary link: showing how bone loss is regulated by sex hormones, and how pregnant mammals activate RANKL to form breast tissue for lactation among other functions,” says Dr. Penninger.

Based on this initial finding, Dr. Penninger’s team went on to show that RANKL played a key role in progestin-driven breast cancer, as well as breast cancer driven by BRCA1 mutations.

“Further researcher revealed how RANKL controls the stem cells in the breast that respond to sex hormones and thereby drives growth of the breast tissue at every menstruation cycle and in particular in pregnancy and lactation,” adds Dr. Penninger.

In the case of breast cancer, RANKL spurs mammary epithelial cells to divide, and helps to maintain the stem cells that give rise to breast tumours.

A dual benefit drug

One in eight Canadian women will be diagnosed with breast cancer in their lifetime according to the Canadian Breast Cancer Network. An estimated 70 to 80 per cent of these breast cancers are hormone receptor-positive (HR-positive), making it the most prevalent breast cancer subtype.

The current standard treatment for HR-positive breast cancer involves surgery and radiation, followed by treatment with aromatase inhibitors for 5 to 7 years. While aromatase inhibitors diminish sex hormones that drive new cancer growth, they can have serious adverse effects on bone health, including increased risk of osteoporosis and fractures.

The now-published clinical trial, led by the Austrian Breast and Colorectal Cancer Study Group, was conducted to see if Denosumab could help in two ways: by reducing these negative effects on bone health, while also improving breast cancer survival outcomes.

“These results are incredibly exciting and will help improve the lives of millions of patients.”
Dr. Josef Penninger

The results reveal that 6 mg of Denosumab every six months — the recommended treatment level for osteoporosis — improved disease-free survival, bone metastasis-free survival, and overall survival among participants. It also effectively reduced bone fractures over the long term.

“Blocking RANKL in breast cancer patients reduces broken bones by 50 per cent, massively improving their quality of life, and even at a very low treatment dose,” says Dr. Penninger. “We now know that RANKL drives breast cancer cell growth, is the critical mechanism behind bone loss, and has also an effect on anti-cancer immunity and immunological rewiring in pregnancy. These clinical results in patients show how blocking RANKL could save the lives of 50,000 women among one million women with the diagnosis of breast cancer.”

Based on the data, the researchers behind the trials are recommending that Denosumab be considered for routine clinical use in postmenopausal breast cancer patients receiving aromatase inhibitor therapy.

These trials were largely based on the foundational research published by the Penninger laboratory, including Kong et al. Nature 1999, Fata et al. Cell 2000, Jones Nature 2006, Schramek et al. Nature 2010, Sigl et al. Cell Research 2016, and Paolino et al. Nature 2021.

Dr. Penninger is now part of a large international prevention trial evaluating Denosumab in young women who carry BRCA1 mutations.

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Respiratory illness peaked in December at Chatham Kent Health Alliance: Suni – Chatham-Kent This Week

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Chatham-Kent Health Alliance officials are reporting a drop in patients visiting the emergency departments with respiratory illnesses between December and January, but admissions from the emergency rooms to the hospitals remain high.

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Caen Suni, the hospital group’s vice president of clinical programs and operations, said patients with illnesses like influenza, COVID-19 and respiratory syncytial virus dropped 50 per cent in January compared to December among children and by one-third among adults.

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“The community is I think essentially working its way through seasonal illness at this point,” he said during a media teleconference Monday.

December also showed a 25 per cent increase over December 2021 for pediatric admissions and of those, 77 per cent were for respiratory illnesses, Suni said.

“That’s impactful and I think that’s what we’ve seen across the health sector in our entire region at this point,” he said.

Suni said the number of people seeking treatment at the emergency departments – which includes patients not admitted – is not “historically high,” but admissions to the hospitals increased in December by three per cent over the previous month.

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This translates to an extra two to three extra patients a day who require a bed. The health alliance also experienced almost 2.5 per cent more admissions in December than any month in the previous year.

However, December also had the lowest daily average of visits to the emergency departments of any month during the Health Alliance’s current fiscal year.

This means a higher proportion of patients require admission to the hospital and patients presenting at the emergency departments are more ill, Suni said.

Since December, the trends are now “pointing towards a decrease,” Suni said, “which we’re thankful for, as the community bounces back from seasonal illness.”

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