Kidney and ureteral stones. Credit: Scientific Animations CC4.0
Sometimes all it takes is a little push. That is the conclusion of a study, published recently in the Journal of Urology, in which doctors used a handheld ultrasound device to nudge patients’ kidney-stone fragments.
As many as 50% of patients who have kidney stones removed surgically still have small fragments remaining in the kidneys afterward. Of those patients, about 25% find themselves returning for another operation within five years to remove the now-larger fragments.
UW Medicine researchers found, however, that patients who underwent the stone-moving ultrasound procedure had a 70% lower risk of such a recurrence.
“I think the main takeaways of this study are removing fragments reduces relapse and using a noninvasive, hand-held ultrasound device to help clear these kidney stone fragments,” said UW Medicine urologist Dr Jonathan Harper, the study’s senior author.
The multisite, randomised and controlled trial was conducted from May 2015 to April 2024. Almost all of the 82 participants were from the UW Medicine or the VA Puget Sound health systems. All had stone fragments that had persisted in their kidneys for months, and their ureters were free of stones and fragments.
In the study, 40 underwent ultrasound treatment to encourage fragments to clear from the kidneys, while 42 control-group members received no such treatment.
With patients awake in a clinic office setting, doctors used a wand that generated ultrasonic pulses through the skin to move the fragments closer to the ureter, where they could be naturally expelled, sometimes with the next urination, Harper noted.
Harper and his co-lead author on the paper, urologist Dr Mathew Sorensen, have worked on this technology and treatment for 15 years. They also use this technology, called burst wave lithotripsy, to blast larger stones into smaller pieces; those successes were published in 2022.
The pushing and breaking technologies are used with the same ultrasound platform.
Harper expressed hope that both clinical uses of the technology would become commonplace. A company, SonoMotion, is commercialising the technology, which was developed at the University of Washington, he added.
“I see a lot of potential in this It could become as common as getting your teeth cleaned. If you have a couple of small stones which could cause future problems, you make an office appointment and in 30 minutes you’re done.
“This could really revolutionise kidney stone treatment,” Harper said.
Human breast milk regulates a baby’s mix of microbes, known as the microbiome, during the infant’s first year of life, in turn lowers the child’s risk of developing asthma, according to a new study published in Cell.
Led by researchers at NYU Langone Health and the University of Manitoba, the study results showed that breastfeeding beyond three months supports the gradual maturation of the microbiome in the infant’s digestive system and nasal cavity, the upper part of the respiratory tract. Conversely, stopping breastfeeding earlier than three months disrupts the paced development of the microbiome and was linked to a higher risk of preschool asthma.
Some components in breast milk, such as complex sugars called human milk oligosaccharides, can only be broken down with the help of certain microbes. This provides a competitive advantage to microbes capable of digesting these sugars. By contrast, infants who are weaned earlier than three months from breast milk and who then rely solely on formula feeding, become home to a different set of microbes –ones that will help the infant to digest the components in formula. While many of these microbes that thrive on formula do eventually end up in all babies, the researchers showed that their early arrival is linked to an increased risk of asthma.
“Just as a pacemaker regulates the rhythm of the heart, breastfeeding and human milk set the pace and sequence for microbial colonisation in the infant’s gut and nasal cavity, ensuring that this process occurs in an orderly and timely manner,” said study co-senior investigator and computational biologist Liat Shenhav, PhD. “Healthy microbiome development is not only about having the right microbes. They also need to arrive in the right order at the right time,” said Dr Shenhav, an assistant professor at NYU Grossman School of Medicine, its Institute for Systems Genetics, and the school’s Department of Microbiology.
For the study, Dr Shenhav, who is also an assistant professor at NYU’s Courant Institute of Mathematical Sciences, worked in collaboration with study co-senior investigator Meghan Azad, PhD, director of the Manitoba Interdisciplinary Lactation Center, and a professor of paediatrics and child health, at the University of Manitoba.
Another key study finding was that the bacterium Ruminococcus gnavus appeared much sooner in the guts of children who were weaned early from breast milk than in those of children who were exclusively breastfed. The bacterium is known to be involved in the production of molecules called short-chain fatty acids, and the formation and breakdown of the amino acid tryptophan. Both tryptophan and its metabolites have been linked to immune system regulation and disruption in previous research, including an increased risk of asthma. The study authors noted that beyond aiding in digestion, an infant’s microbiome plays a crucial role in the immune system’s development.
The study tracked the ebb and flow of microbes in the guts and noses of infants during the first year of life, as well as details on breastfeeding and the composition of their mothers’ milk. All the children and their mothers were participating in the CHILD Cohort Study, a long-term research project that has been studying the same 3500 Canadian children at different stages of life from the womb well into adolescence.
The data provided by the CHILD Cohort Study enabled researchers to detangle the impact of breastfeeding on an infant’s microbiome from a range of other environmental factors, including prenatal smoke exposure, antibiotics, and the mother’s asthma history.
Even when these factors were accounted for, they found that breastfeeding duration remained a powerful determinant for the child’s microbial makeup over time. They also used these microbial dynamics and data on milk components to train a machine learning model that accurately predicted asthma years in advance. Finally, they created a statistical model to learn causal relationships, which showed that the primary way breastfeeding reduces asthma risk is through shaping the infant’s microbiome.
“The algorithms we developed provide valuable insights into microbial dynamics during an infant’s first year of life and how these microbes interacted with the infant,” said Dr Shenhav. “These insights allowed us to move beyond identifying associations, enhancing our ability to make predictions and explore causal relationships.
“Our research highlights the profound impact of breastfeeding on the infant microbiome and breastfeeding’s essential role in supporting respiratory health. By uncovering the mechanisms behind the protective effects of breast milk, as demonstrated in this study, we aim to inform national guidelines on breastfeeding and weaning from breast milk in a data-driven manner.
“With further research, our findings could also contribute to developing strategies to prevent asthma in children who cannot be breastfed for at least three months,” she added.
Researchers discovered a drug that safely and effectively helped cancer patients when they suffered from cachexia, a common condition related to cancer that involves weight loss and muscle wasting.
The results of the randomised phase 2 clinical trial, which included 187 individuals who experienced cachexia with pancreatic (32%), colorectal (29%) or non–small-cell lung (40%) cancer, appear in the New England Journal of Medicine. Richard Dunne, MD, MS, a Wilmot Cancer Institute oncologist and cachexia expert was part of the large group of investigators who ran the nationwide clinical trial.
Cachexia involves loss of appetite and weight, muscle-wasting, fatigue, and weakness. It affects more than 50% of people who have cancer, and currently there are no FDA-approved treatments.
Scientists discovered that the monoclonal antibody ponsegromab blocks a hormone known as GDF-15 that regulates appetite and body weight. The patients in the trial had elevated levels of GDF-15, a primary driver of cachexia, and ponsegromab improved many aspects of cachexia and its symptoms.
Patients were randomised to receive ponsegromab at doses of 100mg, 200mg, or 400 mg, or to receive placebo. At 12 weeks, patients in the ponsegromab groups had significantly greater weight gain than those in the placebo group, with a median between-group difference of 1.22 kg in the 100mg group, 1.92 in the 200mg group, and 2.81 in the 400mg group. Improvements were observed across measures of appetite and cachexia symptoms, along with physical activity, in the 400mg ponsegromab group relative to placebo.
Drugmaker Pfizer supported the study, and released this news. Side effects were minimal, Dunne said, and in fact ponsegromab appeared to be safer than common appetite stimulants used by cachexia patients.
“This is super exciting,” said Dunne, an associate professor of Medicine at the University of Rochester Medical Center. “This study is an important step in providing treatment for the hundreds of thousands of patients who suffer from poor quality of life due to cachexia.”
Several academic medical centres participated in the clinical research, which was led by John D. Groarke, MB, BCh, MPH, at Pfizer. Investigators are continuing to study GDF-15 and the importance of the biomarker in several types of cancer. Other clinical trials are also testing additional cachexia treatments that do not target the GDF-15 pathway.
Professor Glenda Gray, internationally known for her research in HIV vaccines and interventions to prevent transmission of HIV from mother to child, received the country’s highest honour, the Order of Mapungubwe, in 2013. (Photo: Biénne Huisman/Spotlight)
By Biénne Huisman
After a decade at the helm of the country’s primary health research funder, Professor Glenda Gray will focus again on doing the science. She tells Spotlight’s Biénne Huisman about her childhood, her passion for research, administering multi-million dollar grants, and a heated argument in the bathroom with an ANC bigwig.
Professor Glenda Gray, the first woman president and chief executive of South Africa’s Medical Research Council (SAMRC), has among others been described as outspoken, credible and tenacious. After a decade at the helm of the SAMRC, Gray retains her reputation for fearlessly speaking truth to power.
“Heading the SAMRC was definitely the best job of my life,” says Gray. “But I am excited about my future, it’s time for another best job. After ten years of doing science administration, it’s time to get back and do the science.”
Perhaps Gray’s fierce spirit was honed in her childhood, growing up in Boksburg on the East Rand, “on the wrong side of the tracks”. She laughs, remembering how American cable news channel ABC sub-titled her first TV interview, due to her strong “East Rand accent”.
Investing in research
From a childhood of counting cents, these days Gray administers multi-million dollar grants and passionately makes the case for greater investment in scientific research.
She says that while South Africa’s health department has competing priorities, ideally it should double or triple its allocation to research.
“We spend a lot of time trying to show the Department of Health how important science is. And so while there is commitment from them, they’re so busy worrying about services; healthcare workers, doctors, hospitals falling down, no equipment, no cancer treatment. And so, sometimes science is seen as esoteric and a luxury.”
Speaking to Spotlight during her lunch break at an SAMRC event in Cape Town, Gray adds: “Science gives you evidence to reduce morbidity and mortality. All the things that change people’s lives; like covid vaccines, ARVs, mother to child transmission interventions, typically these stem from research. And so, you can only improve outcomes if you fund research. Currently, the SAMRC gets around R750 million from government a year; in my view, around R2 to 3 billion a year is needed to really make profound investments in research.”
Supplementing the funding from the government, the SAMRC has scores of international funders and collaborators, such as the United States National Institutes for Health. One concern with such international donor funding is that local research may end up pandering to agendas set abroad.
Gray rejects this suggestion. “We [the SAMRC] always fund the ten most common causes of mortality and morbidity in South Africa. So the funders who work with us have to agree on funding what we deem our priorities.”
One of these priorities is transformation. “So I spent ten years of my life changing who we funded, where we funded, how we funded; changing the demographics of the SAMRC, creating an executive management committee that was diverse, and being able to attract a great black scientist [Professor Ntobeko Ntusi] to take over from me,” says Gray.
While having passed the public mantle onto Ntusi in July, the paediatrician and renowned HIV vaccinologist, named one of Time magazine’s 100 most influential people in 2017, will continue her HIV vaccine research. Gray is heading a major USAID funded study aimed at “galvanising African scientists, mostly women, into discovering and making an HIV vaccine.” She also holds tenure as a distinguished professor at the University of the Witwatersrand’s Infectious Diseases and Oncology Research Institute.
Give and take
Speaking to Spotlight, Gray reflects on managing the political side of the SAMRC – the intersection between politics and science: “As the president of the MRC, you have to be very brave and you have to be able to speak truth to power. Sometimes it’s hard, and sometimes it’s easy.”
This, she says, is a dance of give and take: “The relationship has to be flexible. Because, sometimes scientists are wrong and politicians are right. Sometimes politicians are wrong and scientists are right. And sometimes both are wrong, and sometimes both are right. And our egos can get in the way. You know: ‘Oh, you took me off the MAC [Ministerial Advisory Committee], now I’m not going to help you’. That’s not the right attitude to have…”
COVID-19 lockdown ruckus
Gray served on the Department of Health’s COVID-19 MAC at the height of the pandemic. In May 2020, she caused a ruckus for breaking away from the committee’s more measured counsel, turning to the press to criticise government’s lockdown regulations as “unscientific”.
She said the hard lockdown was causing unemployment and unnecessary hardship and malnourishment in poor families. Later as the hard lockdown started to lift, she spoke out against government’s continuation of restrictions on school going, the sale of certain foods and clothes like open-toe footwear, and the limits on outdoor exercise. “It’s almost as if someone is sucking regulations out of their thumb and implementing rubbish, quite frankly,” she told journalists at the time.
Then health minister Dr Zweli Mkhize rebuked Gray’s claims and sidelined her in the MAC before excluding her from a newly constituted MAC in September. The acting Director-General of Health, Anban Pillay, wrote to the SAMRC board urging them to investigate Gray’s conduct. As the fray deepened, the SAMRC board failed to back Gray. The council’s boardwas was acting in a “sycophantic manner aimed at political appeasement”, lamented a guest editorial published in the South African Medical Journal.
Despite this public falling-out, the following year, in February 2021, Gray worked with Mkhize to bring vaccines to South Africa’s healthcare workers.
“So basically at that stage government didn’t have a vaccine programme, and I bailed them out,” she tells Spotlight.
In February 2021, results from a clinical trial showed that the Oxford AstraZeneca COVID-19 vaccine – then intended for rollout in South Africa – performed poorly in preventing mild to moderate illness caused by the Beta variant of SARS-CoV-2, which was dominant at the time.
Gray says she was approached by Mkhize about an alternative vaccine – to which she responded by facilitating the procurement of 500 000 doses of the Johnson & Johnson vaccine through personal connections. These were officially rolled out to healthcare workers on February 17, when President Cyril Ramaphosa received his jab at the Khayelitsha District Hospital. Spotlight previously reported in more detail on the procurement of those first 500 000 doses.
“The vaccines arrived in Johannesburg at about midnight,” Gray recalls. “Then the plane with the president’s vaccine touched down in Cape Town at 12:20pm; and we had to rush it to Khayelitsha to have him vaccinated at one o’clock”.
A bathroom row with a minister
Gray is no stranger to fighting for policies and treatments based on scientific evidence. She recalls an altercation with former health minister Nkosazana Dlamini-Zuma in a bathroom at the presidential residence in Pretoria (Mahlamba Ndlopfu) in the late 1990s – the era of AIDS-denialism under then President Thabo Mbeki.
“Thabo Mbeki had a national AIDS plan and they were about to publish it. So there was a meeting; we were presenting, and we had data that mother to child transmission interventions were affordable, or that it was actually cheaper to give ARVs to a pregnant woman, than to treat a child who is HIV positive. But they kept on saying it was unaffordable, and that they wouldn’t be doing it. And then, when I saw Dlamini-Zuma in the bathroom, I got into a fight with her and said: ‘but it is affordable!’”
Early years in Boksburg
One of six children born to a “maverick father”, whip-smart but taken to getting involved in crazy schemes, and a mother who later in life became a Baptist minister, Gray says they grew up poor.
“My parents would often run out of money in the middle of the month, having to scrounge for food, borrow milk or buy on the book (credit arrangements). So I know what it’s like to be on the other side of privilege.”
Gray relays how neighbours would drop by at her childhood home to borrow cups of sugar, to spy on their family – as, during apartheid, her father would entertain friends of colour.
Gray matriculated from Boksburg High School in 1980. The next year she enrolled for medical school at Wits, working part-time to pay her way: “I worked at an ABC shoe store, Joshua Door, selling furniture, making Irish coffees at Ster Kinekor, waitressing…”
In 1993, as HIV exploded across the country; pregnant with her first child, Gray watched her own stomach expand while treating HIV-positive expectant mothers at Chris Hani Baragwanath Hospital. “In those days, there were no ARVs for children,” she recalls. “And so women had to navigate this joy of a new life, with the fact that death was looming over them.”
Today, Gray has three children and lives in Kenilworth in Cape Town.
Commenting on her reputation for standing up to pressure, she smiles. “My tongue has gotten me into trouble. How do I feel about that? I just want to make sure that as scientists we let politicians and society know the data and the evidence. I feel passionate about translating science, I feel passionate about evidence. I feel passionate about science changing the world.”
