A major new study, led by Queen Mary University of London and funded by the National Institute for Health and Care Research (NIHR) has been published in The Lancet Public Health. It found that out of the five million surgical procedures performed each year by the NHS, around 300 000 are carried out on individuals considered high-risk, and within 90 days of surgery, these high-risk patients account for:
four out of five deaths
over half of all hospital bed days
nearly one-third of emergency readmissions
While surgery is safer than ever for most people and remains the best treatment option for many conditions, this study highlights the urgent need to identify high-risk patients earlier, to provide care that is better tailored to their individual needs, and for doctors and patients to have more open, honest conversations about the risks and long-term outcomes for surgery at an individual level.
It also shows that high-risk patients, who tend to be older and live with several long-term health conditions such as heart disease, have poor outcomes not because of technical failings in surgery or anaesthesia, but due to post-operative complications relating to chronic health conditions, age and frailty. Therefore, the findings demonstrate the need for greater investment in specialist perioperative services that focus on the care of older, high-risk patients before, during and after surgery.
Rupert Pearse, Professor and Consultant in Intensive Care Medicine at Queen Mary University of London and Barts Health NHS Trust, and co-lead of the study said: “While surgery is safer than ever before, our findings clearly show that high-risk patients are more likely to have poor outcomes and experience harm after surgery than those deemed low-risk.
“Although these patients make up fewer than one in ten surgical cases, their numbers are increasing as the population ages and more people live longer with chronic illness. It is therefore vital that we work to improve care for this group of patients, pre- and post-surgery, including having open conversations with patients about the individual risk of their procedure.”
He continues: “For many years, surgical success has often been judged by survival at thirty days. Our study shows that this measure does not give the full picture of what happens to many high-risk patients in the months and years after surgery. By looking at longer-term survival and other factors such as time spent in hospital and quality of life, we could make a real difference to patients and potentially help relieve pressure on the wider NHS.”
The study is one of the largest analyses of surgical outcomes ever carried out in the UK. It analysed health records from 13 million adults who had 16.1 million surgical procedures in England, Scotland and Wales between 2015 and 2019.
Mark Bishop, Deputy Chairperson of the Hospital Association of South Africa (HASA) and Chief Commercial Officer at Lenmed Health Group, is a prominent voice in South Africa’s private healthcare sector. With more than three decades of experience, he brings deep insight into hospital management, healthcare systems and patient-centred care. Known for his strategic leadership and operational expertise, Bishop has played a key role in driving sustainable growth and innovation within Lenmed and the broader healthcare industry.
In this Q&A, Mark shares his perspectives on HASA’s role, sector priorities and the future of healthcare in South Africa.
Q: As HASA Deputy Chairperson, what do you see as the organisation’s core contribution to strengthening South Africa’s health system?
A: The private hospital sector plays a vital role by providing essential facilities and capacity for healthcare professionals to deliver quality care. Over the past four decades, private hospitals have expanded bed capacity while public sector capacity has not kept pace with population growth. This helps meet rising demand and relieves pressure on an already overburdened public system. All industry players, providers and funders, will need to consider the best collaborative approach, and the impact this would have for all and not just concentrate on the impact on their own organisations.
Q: What are HASA’s priorities for long-term sustainability of the healthcare sector?
A: Sustainability depends on affordability across both public and private healthcare. Cost drivers are the same, staffing, infrastructure and medical equipment. Improving the utilisation of limited resources across the system is critical to meeting growing healthcare needs.
Q: How do you view the current medical schemes landscape?
A: Medical schemes operate in a challenging environment characterised by stagnant membership, an ageing population, increasing chronic disease and rising costs driven by advances in medical technology. This is a consequence of a raft of incomplete reforms over the years that together have placed a heavy burden on medical scheme members. Rectifying this could take considerable expense off them.
Q: What reforms could improve affordability while maintaining quality?
A: Increasing medical scheme membership would reduce unit costs. Mandatory medical scheme covers for employed individuals, as recommended by, would expand access to care, reduces pressure on public hospitals and support progress towards universal healthcare. This would need to be done with changes to the reimbursement processes for private care, reducing the impact of fee for service and aligning with quality improvements.
Q: Your career spans 30+ years in private healthcare. What have been the most significant shifts?
Over the years, we have seen patients become more informed about their healthcare needs, medical scheme requirements have evolved and the private healthcare landscape change significantly through consolidation in medical aids.
Q: Where do you see the greatest opportunities for collaboration?
A: The private sector has spare capacity that could be used to treat publicly funded patients. Public-private partnerships, shared infrastructure and co-located facilities offer opportunities to reduce waiting times, lower costs and improve access to care. The caution, is that this needs to align with a national strategy to increase the rate at which nurses are trained, the reality is that both public and private sectors struggle to do the limited professional nurse resources.
Q: What motivates you about your role at Lenmed?
A: Lenmed’s vision of building healthier, more prosperous communities resonates with me. Our hospitals maintain a strong community focus, rooted in the founding of Lenmed Ahmed Kathrada Private Hospital over 40 years ago. Private healthcare is at a tipping point and collaboration across the sector will be essential to grow access and create a sustainable, high-quality healthcare system.
Dr Sheetal Kassim, the site lead for the Desmond Tutu Health Foundation’s clinical trial site at Groote Schuur Hospital. (Photo: Nasief Manie/Spotlight)
By Elri Voigt
A cutting-edge, South African-led HIV vaccine trial built on decades of research recently kicked off in Cape Town. Spotlight unpacks what exactly is being studied, and how the resilience, tenacity and urgency of a group of dedicated South African researchers made it possible.
Antiretroviral medicines can suppress HIV in the body and keep people healthy, but we do not yet have a viable cure for HIV or an effective vaccine. It is not for lack of trying. For decades now, researchers across the globe have been working hard to develop a vaccine against HIV. While there have been several major disappointments along the way with vaccines failing in large studies, a new clinical trial in South Africa might soon find vital answers that could reinvigorate the field.
The study was originally set to start in 2025, but researchers had to pivot and find new funders when the United States abruptly terminated much of its international research funding. After some scrambling, a stripped-down version of the study has now started. Rather than being cowed by having to delay, and reduce the size of the study, it seems that forging ahead without US support have sparked a pervasive sense of optimism.
“It feels like the most coherent, involved clinical trial I’ve ever been involved in – so that’s why I’m so excited. I feel like it’s going to lead to big things because it’s bringing so many people with it,” says Professor Penny Moore, a leading virologist who is heading up the laboratory work for the study.
That optimism is tangible at the clinical trial site in the Old Main Building at Groote Schuur Hospital in Cape Town. During our visit, one can’t help noticing how the Desmond Tutu Health Foundation’s signature rainbow logo and colourful walls and furniture breaks through the dark hospital corridors and ancient elevators.
The colourful waiting room at the Desmond Tutu Health Foundation’s clinical research site at Groote Schuur Hospital where a South African led HIV vaccine trial is taking place. (Photo: Nasief Manie/Spotlight)
Like the sugar coating on a Smartie
In the clinical trial, called BRILLIANT 011, researchers are testing two immunogens, says Dr Sheetal Kassim. She is the site lead for the Desmond Tutu Health Foundation’s clinical trial site at Groote Schuur Hospital and Principal Investigator for the trial. An immunogen is an engineered agent designed in a laboratory, she explains, to cause a specific immune response. The aim of this trial, Kassim says, is to see if these two immunogens are able to trigger the development of cells that have the potential to later become special immune cells called broadly neutralising antibodies.
Once HIV is in someone’s body, it is able to stick around mainly by taking over immune cells called CD4 cells. It evades the immune system by constantly mutating so the antibodies sent to find it don’t recognise it. Eventually the infected CD4 cells burst and die, but HIV keeps replicating, weakening the immune system.
Broadly neutralising antibodies are special antibodies that can recognise and fight a range of different HIV strains, no matter how much it has mutated, says Moore.
HIV is covered in something called glycans that make it hard for antibodies to reach it, she explains. Think of these glycans as the hard sugar coating around a Smartie. A broadly neutralising antibody can recognise the parts of the virus that won’t change when it mutates. This allows the broadly neutralising antibody to be able to reach through that hard outer coating, bind to the virus and destroy it.
Two immunogens, given at the same time
In late January, the researchers enrolled the first of an expected 20 healthy participants, who do not have HIV, and are at a low risk for getting HIV. By mid-February, seven participants had received their first shots.
It is a phase one study, which is to say it is still very early days. A phase one trial looks at the safety of a drug or vaccine in a small number of individuals, while a phase two trial looks at safety in slightly larger groups and gives some early indication of efficacy. A phase three trial is much larger and looks mainly at efficacy.
The researchers are testing the immunogenicity – essentially the ability to elicit an immune response against HIV – and safety of the two immunogens in humans for the first time. A special adjuvant – known as SMNP – is being added to the agents to enhance their effect.
The hope is that the study results will help identify a potential vaccine candidate to test in future, larger studies, says Kassim. “We’re not going to come out of this study and say we have a vaccine that can prevent or cure HIV,” she says. “But we will have information on these immunogens that will help us in the future.”
It has already been shown that the two immunogens can target the type of antibody cells that have the potential to become broadly neutralising antibodies and essentially switch them on. Think of it as a talent finding agency, says Kassim, that can find the next “star” that can become an important broadly neutralising antibody.
The two shots are injected into the muscle of the arm on three separate visits, she says. The first is given after a rigorous health screening. The second is given one month later and the final dose is given three months later. Doing it this way, primes the immune system with the first shots and then the doses that follow boost the initial effects.
Putting ‘the puzzle pieces together’
Research studies like this one is still in the “experimental medicine” phase, Professor Linda-Gail Bekker, CEO of the Desmond Tutu Health Foundation, tells Spotlight. She says results from this study will help “put the puzzle pieces together” to get a clearer picture of which immunogens should eventually be tested in a phase three efficacy trial.
The trial is novel because of the use of two immunogens instead of one. Professor Glenda Gray, Chief Scientific Officer at the South African Medical Research Council (SAMRC), refers to it as an “ambitious and aggressive approach”. She tells Spotlight that usually researchers follow a sequential pattern, testing one immunogen, then another and eventually testing them together. The problem with this is that if they don’t work together, you’ve lost up to five years of research.
“We also have this philosophy of ‘failing fast’,” Gray says. “[I]nstead of wasting money and time and effort, we need to know whether our strategy is going to work or not in the beginning.”
A proudly South Africa trial
Beyond the cutting-edge science, it’s clear that what makes this trial so unique is the people involved.
Bekker describes the trial as “proudly South African”. She says: “It’s just terrific that we’re doing this end-to-end. We’re involving the community, the recruiters are people from the country, the people who are taking the blood are people from the country, the people who are doing the laboratory science are from the country, and we’re doing it for people in our country.”
Moore adds: “We’ve got so many people in the background working on these trials at the clinical sites and here in my lab…There’s this huge mass of people all working together on this trial.”
BRILLIANT 011 is one of 22 trials currently running at the Groote Schuur Hospital site, Henriette Kyepa the Unit Manager for the site, tells Spotlight. The doors open at 07:00 and the last participant leaves by 15:00, and since at least 40 participants are being seen each day, she describes the goings on as “bustling”.
The hospital has an illustrious medical history, with the first human heart transplant having been performed in the Old Main building – the Christiaan Barnard Heart Museum is just a few floors down. The Desmond Tutu Foundation’s research site has been operating at the hospital for more than 10 years.
During a tour of the unit, Spotlight was led through a waiting area, pharmacy, and two nursing areas – where patient’s vitals are checked and data captured. Staff manning the different stations were busy, but friendly and took requests for photographs in their stride. There are four doctors’ rooms and a procedure room, equipped with things like a crash cart in case anyone has a bad reaction to a drug or device that’s being tested. The site also includes private counselling rooms and a purple, gender inclusive bathroom. Down the hall, there is a hospital ward and a small laboratory, which is shared with the University of Cape Town Clinical Research Unit, for patients that need timed blood draws for studies where drug levels are being monitored.
But before they come to the site, the first point of contact for many potential trial participants – for BRILLIANT 011 and other studies – are the community recruiters. This is a team of three outreach workers led by Amelia Mfiki, who is the community liaison officer for the Desmond Tutu Health Foundation and lead recruiter. Their job is to keep the local communities updated on what the site is doing, get their feedback and to find participants who fit the eligibility criteria for different studies.
If someone is interested in a study, Mfiki explains, they are sent to the site for an information session, where the trial, eligibility criteria and the commitment required to participate is clearly unpacked. If they meet the criteria and want to participate, they go through a further informed consent process and screening. With a big smile, she tells Spotlight there has been a lot of requests for information about the BRILLIANT 011 trial.
Once enrolled, clinical trial participants will spend a lot of time with the nursing staff. Among them is Viwe Soko, a senior nurse who says “making people smile” is part of his job.
How they’ll test if it works
The BRILLIANT 011 trial participants will need to come back roughly two weeks after each jab to have white blood cells – which contain the cells that can become broadly neutralising antibodies – extracted from their blood through a process called leukapheresis. This is how the researchers are looking for those “star” antibodies that have the potential to become broadly neutralising antibodies.
Basically, the leukapheresis machine draws a participant’s blood and runs it through a centrifuge that separates the white blood cells from all the other cells in the blood, explains Moore. The white blood cells are collected into a sterile blood bag, while the rest of the blood goes back into the participant. (Here’s a useful video showing how it works).
Hundreds of millions of white blood cells are collected each time a participant goes through this process, according to Moore. “The reason we need a crazy number [of cells] is because the responses that we’re looking for are rare as hen’s teeth,” she says.
The cells are then processed in the laboratory at Groote Schuur Hospital and sorted into different tubes containing 20, 50 and 100 million cells respectively, frozen, and then sent more than 1 000 km away to Moore’s laboratory at Wits University in Johannesburg.
Once there, the thawed antibodies are run through a special machine called a flow cytometer, which is able to spit out individual cells of interest via an ultra-thin stream. The cells are mixed with a dye to make them easy to spot, says Moore. Then a laser and computer, under the supervision of a highly trained scientist sorts the cells to isolate the types of antibodies they’re interested in.
These precursors of the broadly neutralising antibodies are “structurally weird”, said Moore, some of them have really long “arms” that can reach through HIV’s hard outer coating, or really short “arms” to get close to it.
At the end of the process, there might be 100 relevant cells which then go through a process called next generation sequencing. The researchers are looking for two specific genetic signatures that will show that the right antibody was produced. Moore likens this to a cell that has “a purple head and an orange arm” and is extremely rare. Once they find all the cells with these signatures, they count them.
At its core, Moore says, they’ll know the immunogens have worked if they find more “cells with purple heads and orange arms” than has been seen in other vaccine trials that only used one immunogen.
“I think this is some of the most important work I’ll ever do,” Moore says. “It feels like 20 years of basic science has finally paid off.”
She has been monitoring the antibody responses for the CAPRISA 002 cohort for the last two decades. It is within this cohort, that a handful of women living with HIV who had naturally produced broadly neutralising antibodies were discovered and since studied. This is part of the foundation on which the BRILLIANT 011 trial has been built.
Because of all the lab work and specialised equipment required, this kind of study is expensive to run. For the study period, it costs about R1 million for each participant to be in the trial, according to Gray. This trial has a budget of R25 million, the bulk of which has been supplied by the Gates Foundation. Some emergency funding from the SAMRC was used to make up the rest.
‘Nobody gets the urgency’ like South Africa
This amount is a far cry from the five-year USAID grant worth over $45 million, that was originally awarded to the BRILLIANT Consortium in 2023. This ambitious African-led Consortium, led by Gray and run out of the SAMRC, had big plans for HIV vaccine research and capacity development across Sub-Saharan Africa. As Spotlight previously reported, the Consortium planned to conduct three HIV vaccine trials, about one a year, and develop laboratory capacity for this kind of research across the African continent.
In the end, they only had the USAID grant for a year, just enough time to set everything up for BRILLIANT 001, a much flashier version of the trial that is currently running. It was set to take place at sites in Uganda, Kenya, Zimbabwe, South Africa and Nigeria, and recruit 60 participants, according to Gray.
“We were actually due to start it [BRILLIANT 001] in February of 2025. And then it was stopped,” Bekker says. “And so, we went through the five stages of grief and finally got to the point of acceptance. And with acceptance came a real sort of verve to try and find alternative funding.”
Essentially, the researchers were racing against the clock on multiple fronts.
The immunogens, which had been donated by labs in the Netherlands and the United States were already in the country and had expiration dates that meant the study could not be delayed indefinitely (in the end the study would start in time for this to no longer to be a concern).
But more importantly there was the roughly eight million people living with HIV in the country.
“I think nobody gets the urgency like a South African,” Bekker says. “It’s very real in our lives that this virus continues to devastate [and] change the lives of people we love and serve and work with. So that sense of urgency is very real within us.”
The team wrote up a new funding proposal and study protocol, which Bekker describes as a much lighter version, “pared down to the absolute bones”. They presented this to the Gates Foundation, which agreed to provide funding for this leaner version, and the team pushed to get everything else in place.
Gray weighs in on how, just as the process was taking off again and the protocol had been submitted to the South African Health Products Regulatory Authority (SAHPRA), which has to review and approve all clinical trials conducted in the country, the adjuvant they had planned to use was recalled by the manufacturer. Luckily, they had had some warning this might happen and had a protocol using another adjuvant ready to go. And just a year after the original trial was meant to start, they were able to kick off BRILLIANT 011.
“No one works in these timelines,” says Gray, adding that part of the reason they were able to pull this off was because of how well the team works together. “Everyone puts in more than their pound of flesh, they work incredibly hard…everyone believes in the kind of programme that we’re trying to put together,” she adds.
‘I want to help my community’
Participants for the 011 trial are reimbursed for their time and travel using a SAHPRA approved model. However, Kassim says there appears to be a more altruistic motive among participants, with some sharing sentiments like: “I want to help people. I want to help my community.”
Bekker notes a similar theme that’s held true over the last two decades of HIV vaccine research. “It’s incredibly encouraging, but it’s also incredibly humbling that, in a country like ours, where people have so many other challenges, that they could … [have] an entirely altruistic motivation, that they are digging deep within themselves and saying: ‘I’m motivated because I want to see an end to the suffering’.”
“If we truly want to bring this epidemic to an end and eliminate transmission, we will need a vaccine,” says Bekker. “And imagine, a world where you could get your vaccination, at age 10 or even younger, and then not have to think about HIV ever again.”
Disclosure: The Gates Foundation is mentioned in this article. Spotlight receives funding from the Gates Foundation but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.
Houston Methodist researchers find antibiotics aid recovery from traumatic brain injury
Source: CC0
What if healing the brain after traumatic injury starts in the gut? In a new study published in Nature Communications Biology, Houston Methodist researchers led by Sonia Villapol, PhD, found that short-term antibiotic treatment significantly reduced neuroinflammation and neurodegeneration following traumatic brain injury (TBI) by altering the gut microbiome in animal models.
“We found that antibiotic treatment following TBI can reduce harmful gut bacteria, decrease lesion size and limit cell death,” said Villapol, an associate professor in the Department of Neurosurgery at Houston Methodist. “Our results support a gut–brain mechanism in which microbiome changes influence peripheral immunity and, in turn, neuroinflammation after TBI.¨
Administering antibiotics cleans the gut of harmful bacteria, allowing beneficial bacteria to flourish. The study found that two helpful bacteria, Parasutterella excrementihominis and Lactobacillus johnsonii, are key to driving cell repair. According to Villapol, they could also be major regulators for peripheral inflammation in the body.
Notably, 70% of immune system regulation is generated by the gut microbiome. During gut imbalance, the bidirectional nature of the brain-gut axis can wreak havoc throughout the entire body.
“Our brains are constantly sending signals to the rest of our bodies. Following a traumatic brain event, those signals can get scrambled and disrupt other organs, including our digestive system,” Villapol said. “If the gut stays out of balance, the brain may have a harder time healing.”
Recent studies indicate that TBI-induced gut microbiome imbalance may even contribute to the development of neurodegenerative diseases like Parkinson’s, Alzheimer’s and dementia.
Villapol’s lab is focused on investigating and developing new neuroprotective treatments to fight inflammation linked with neurodegenerative disease. “If we can break neuroinflammation in the acute or chronic stage, we can reduce the risk of developing Alzheimer’s or dementia,” said Villapol.
The next phase of the research will focus on bioengineering P. excrementihominis and L. johnsonii to further develop precision therapies to reduce neuroinflammation.
Findings could help patients avoid side significant effects and improve quality of life
Credit: Darryl Leja National Human Genome Research Institute National Institutes Of Health
A new study led by UCLA Health investigators suggests that adding hormone therapy to post-operative radiotherapy may provide little survival benefit for most men with prostate cancer, especially for those with very low PSA levels before treatment.
The researchers found that for men with low PSA levels prior to radiotherapy, adding hormone therapy, whether short-term or long-term, did not improve overall survival. Men with higher PSA levels before radiation may see modest improvements in survival and metastasis-free survival, suggesting hormone therapy may be beneficial primarily for this higher-risk group.
The results were published in The Lancet and presented by Dr Amar Kishan, professor and executive vice chair of radiation oncology at the David Geffen School of Medicine at UCLA, during the plenary session of the American Society of Clinical Oncology Genitourinary Cancers Symposiumin San Francisco.
“Hormone therapy, which impacts the ability of testosterone to stimulate prostate cancer growth and repair, has been shown to improve outcomes when combined with radiotherapy in men whose prostates are still intact. However, whether it has a similar benefit for men receiving radiotherapy after prior surgery has remained unclear,” said Kishan, first author of the study and co-director of the cancer molecular imaging, nanotechnology and theranostics program at the UCLA Health Jonsson Comprehensive Cancer Center. “At the same time, hormone therapy carries significant side effects, including severe fatigue, hot flashes, sexual dysfunction, weight gain, bone loss and metabolic changes that can increase cardiovascular risk. Our findings show that for most men with detectable but low PSA levels (<0.5 ng/mL), after surgery to remove the prostate, post-operative radiotherapy is highly effective on its own. By safely omitting hormone therapy in these patients, we can potentially spare them months of treatment that may substantially affect their quality of life without extending survival.”
To better understand the impact of hormone therapy in this setting, the researchers conducted a large-scale, individual patient-level meta-analysis through the MARCAP Consortium, an international collaboration co-led by Kishan that is designed to evaluate long-term outcomes across randomized clinical trials.
The team analysed data from 6057 men enrolled in six randomised trials comparing post-operative radiotherapy alone to radiotherapy combined with either short-term (4-6 months) or long-term (24 months) hormone therapy. By pooling individual patient data rather than relying on summary trial results, investigators were able to examine outcomes in greater detail, including how pre-radiation PSA levels influenced treatment benefit.
Patients were followed for a median of nine years, allowing researchers to assess long-term overall survival, metastasis-free survival and recurrence outcomes. The analysis also enabled direct comparisons between short-term and long-term hormone therapy to determine whether extending treatment duration improved outcomes.
The researchers found that overall, 83.6% of men who received post-operative radiotherapy alone were alive after 10 years, compared with 84.3% for those who received post-operative radiotherapy plus hormone therapy.
Researchers found that pre-radiotherapy PSA levels, a measure of prostate-specific antigen in the blood after prostatectomy, played a crucial role. Men with low PSA levels before radiotherapy (≤0.5 ng/mL) saw no benefit from hormone therapy. In contrast, men with higher PSA levels showed modest improvements in survival, suggesting that hormone therapy may only be worthwhile for those with elevated PSA.
The study also examined the duration of hormone therapy. Short-term therapy did not improve overall survival, though it slightly reduced the risk of cancer spreading. Long-term therapy showed a small survival benefit, particularly for men with higher PSA levels after prostatectomy. However, the team’s statistical analysis demonstrated that extending short-term therapy to long-term therapy did not further improve survival, although it did modestly lower the risk of metastasis.
“Our goal is always to treat the cancer while minimizing harm,” said Kishan. “This study helps us move toward more personalised care for men with prostate cancer. By better identifying who truly benefits from hormone therapy, we can make treatment smarter, reduce unnecessary interventions and focus on improving patients’ overall well-being.”
Building on those findings, ongoing research is working to further refine that approach. Trials such as the BALANCE Trial aim to pinpoint biomarkers that can identify which men are most likely to benefit from hormone therapy after surgery, helping tailor treatment decisions even more precisely.
In a leap for personalised medicine, scientists have discovered a simple and valuable way to improve brain cancer surgeries.
Taylor Furst, MD, observes a brain mapping procedure in progress at the University of Rochester’s Strong Memorial Hospital. Credit: Matt Wittmeyer
When removing cancerous tissue in the brain, neurosurgeons often use “awake brain mapping” to minimise the risk of causing unintended disruptions to a patient’s quality of life while removing as much tumour as possible. This practice, which has been used for decades, involves waking a patient up mid-surgery to test their neurocognitive functions in real time by stimulating the brain surface and assessing for functional changes.
A new study published in the journal Science Advances details a promising new avenue toward improving awake brain mapping results by investigating the tiny, nearly imperceptible variabilities in patient behaviour that occur during the procedure. This work, led by Carnegie Mellon University researchers, points to a future where brain surgeries are not just safer, but more precisely tailored to protect each patient’s speech, movement and quality of life.
How awake brain mapping works
As cancer grows in the brain, it rarely keeps to itself. Cancerous cells can be found in the seemingly healthy brain tissue surrounding a tumour, presenting neurosurgeons with a dilemma. They need to remove as much tissue infiltrated by cancer as possible, but they also need to avoid the removal of too much tissue since it can cause permanent harm to a patient’s ability to hold a fork or a conversation.
During awake brain mapping, surgeons gently stimulate the brain with small electrical impulses while the patient completes planned tasks. One of the most common applications of awake brain mapping is to identify where language is represented in a patient’s brain, which is done by having the patient name pictures or read words while their brain is being stimulated. If the patient can respond quickly and correctly, the clinicians know the part of the brain they stimulated can be safely removed. If the patient slurs or becomes unable to speak, then that part of the brain may be essential for language. Surgeons require a significant amount of experience to understand the nuances of this complex technique.
While the method may sound extreme, the brain has no sensory nerves, so patients do not feel their brain surgery as it is happening. Recent research also shows that for some types of brain cancer, improving a patient’s quality of life after surgery extends their expected survival into the future. This means that anything that can make awake brain mapping even more effective will translate into improved outcomes for brain cancer patients.
New measures show how slight changes in procedure affect patient behaviour
Based on a decade of research, the study authors uncovered new insights from examining the answers patients get wrong – and right – while undergoing awake brain mapping.
“We found that if you measure both the types of errors that patients make, as well as how fast they respond even when they do not make errors, more granular inferences can be drawn about language organization from an awake brain mapping procedure,” said Bradford Mahon, a cognitive neuroscientist at CMU’s Neuroscience Institute and Department of Psychology and senior author of the study. “We also found that physical parameters of the direct electrical stimulation delivered to the patient’s brain – such as its duration, and when it started and stopped relative to the task the patient is performing – were tightly related to small changes in patient behaviour that we could measure.”
Mahon and his team don’t yet know exactly what combination of parameters should be used to maximise the effect of direct electrical stimulation mapping. But they have discovered an intriguing signal hidden inside of the data that, until now, has gone unnoticed.
“What we have measured and formalised in our study is how slight changes in the awake mapping procedure can cause slight changes in patient behaviour. This is exciting because it is a new and meaningful signal that can be extracted from the data already being generated during awake brain mapping procedures,” said Mahon.
A new level of personalised medicine
The new study suggests that awake brain mapping may offer more informative and more personalized guidance for surgery than has been possible in the past.
For example, stimulating a particular area of the brain might reliably cause an error, never affect behaviour at all, or – more subtly – slow a patient’s response without causing an obvious mistake. In some cases, stimulation may affect behaviour at one moment, but not when tested again just seconds later.
“In other words, brain mapping isn’t always black or white,” said Belkhir. “Sometimes the most important information lives in the grey area.”
The nuance matters because every brain is different, which means every surgery is different, too. Understanding why stimulation has variable effects across different patients, and even within the same patient from one part of the surgery to another part of the surgery, may be key to protecting outcomes for future patients.
“Surgeons are seeking to optimise the balance between removing all of the cancerous tissue while preserving critical functions that may be represented by nearby brain regions,” said Mahon. “This research shows that by measuring aspects of patient performance that were previously not considered relevant for awake brain mapping, even better predictive models of brain organisation can be developed.”
If clinical teams have better predictive models personalised to each patient, then the consequences of different surgical approaches on postoperative neurocognitive function can be simulated. This allows for patients and their caregivers to personalise decisions to what is most important to the patient.
In other words, Mahon said, a business manager may consent to a surgery that may diminish their motor skills, but not their speech, whereas a concert violinist may prefer the opposite.
Bringing standardisation to awake brain mapping surgery
Another important development from this research is the startup company MindTrace, which has built an integrated software platform that supports neurocognitive testing before, during and after surgery. It is working to build a longitudinal dataset of patient outcomes that will be used to train forecasting models.
Tyler Schmidt, MD, study co-author and neurosurgeon at the University of Rochester, has used MindTrace in over a dozen awake surgeries since its release this year.
“In the beginning of brain tumour surgery, it used to be, ‘Can we remove any of this tumour safely?’” said Schmidt. ”But now in some brain tumour cases it’s, ‘Can we get you back to work potentially? Can we keep your quality of life close to what it was prior to your diagnosis? Can we hone in on the things that are most important to you and then try and protect them while getting the same oncological outcome?’” said Schmidt. “I think it’s a positive paradigm shift in how we take care of this patient population.”
The options today are measurably better than they were even 20 years ago. Clinicians now understand how to maximise the likelihood that patients have the best possible outcomes from brain cancer surgery.
“Ultimately, we are contributing toward the set of tools that clinicians will have that will enable them to map the brain with even greater confidence and precision, and personalised to each patient,” said Mahon. “The big goal is to translate scientific insights into solutions that improve people’s lives. We will meet that goal by building tools that enable the best possible outcomes in neurosurgery patients, both in terms of neurocognitive function and quality of life, and ultimately, in terms of survival.”
Ivermectin was originally celebrated as a revolutionary treatment for parasitic disease in humans and animals. It has since evolved into a focal point of misinformation and heated debate.
During the early part of the COVID pandemic, it was touted on social media as a miracle cure for the virus, despite a lack of robust evidence.
The drug is a small organic chemical that can be extracted from the bacterium Streptomyces avermitilis. This bacterium grows in the soil, and was first found near the grounds of a Japanese golf course.
It was first approved for use in animals in 1981 and in humans in 1987. It’s now available in various brands as tablets and creams you apply to the skin.
Assessing the evidence
Governments use human clinical trials to decide whether to approve a medicine for sale.
But clinical trials aren’t the highest level of evidence to inform best practice and guide decisions. For that, there are Cochrane reviews.
A Cochrane review brings together a panel of experts who collate and assess all the relevant evidence on a medication. It takes data from multiple clinical trials, and other studies, and evaluates it following clear and structured steps. It’s able to examine and critique study designs to identify bias and reject bad data.
Cochrane reviews are also regularly updated to take into account new information. The result is a summary that is considered the highest level of evidence to guide decision-making.
So what do Cochrane reviews say about ivermectin for different conditions?
Ivermectin is used to treat a variety of parasitic worm infections. These include the round worms Ascaris lumbricoides, Strongyloides stercoralis, Wuchereria bancrofti, and Brugia malayi.
The latter two worms cause the disease lymphatic filariasis (or elephantiasis) which causes severe swelling in the arms, legs, breasts and genitals.
When ivermectin is used to treat Strongyloides stercoralis, the Cochrane panel found it is better than albendazole and had fewer side effects than thiabendazole.
For Ascaris lumbricoides, the panel concluded ivermectin was as good as albendazole and mebendazole.
For treating lymphatic filariasis, a Cochrane review found ivermectin or diethylcarbamazine should be standard treatment in combination with albendazole.
Rosacea
The Cochrane review for rosacea evaluated 22 different treatments for this skin condition, including a variety of drugs, as well as light therapy, cosmetics and reducing the intake of spicy food.
It concluded that ivermectin applied to the skin was more effective than a placebo, and a bit better than the other standard medication, metronidazole.
Scabies
Cochrane has two reviews on the use of ivermectin for scabies. One specifically evaluated ivermectin and permethrin as treatments. The other evaluated all available treatments for scabies.
The first review concluded both permethrin and ivermectin were just as effective, regardless of whether the ivermectin was administered orally or directly onto the skin.
In contrast, the second review concluded ivermectin does work but topical permethrin appeared to be the most effective treatment.
Malaria
The Cochrane panel looked specifically at whether ivermectin could reduce transmission of the malaria parasite, rather than as a treatment.
Unfortunately there was just a single clinical trial to use as evidence. In that trial, residents of eight villages were given ivermectin and albendazole together, with follow up doses of just ivermectin. The researchers then looked at the rates of child infection over 18 weeks.
Even though the trial didn’t show ivermectin prevented infection, due to the high risk of bias in it, the Cochrane panel couldn’t conclude either way whether ivermectin worked or not.
River blindness
River blindness is caused by another parasitic worm called Onchocerca volvulus.
The Cochrane review concluded there was a lack of evidence either way to know whether it works to prevent infection-based visual impairment and blindness.
It evaluated the data from four clinical trials and two large community-based studies.
One of the reasons the panel was unable to make a firm conclusion was because it thought the drug may work differently against different strains of the parasite and in people of different ethnicity.
Cancer
There are no Cochrane reviews on ivermectin’s use for cancer because clinical interest in the drug for this condition is just starting.
There is a current clinical trial that is evaluating ivermectin in combination with antibody-based drugs for breast cancer.
Early results showed the combination of antibody drugs with ivermectin was safe to patients, but no efficacy data has been published.
COVID
The Cochrane panel rejected the data for seven clinical trials and included 11 other trials. Rejected trials included those which compared ivermectin against other drugs which were known to not be effective against COVID, such as hydroxychloroquine.
The review concluded there was no evidence to support the use of ivermectin for the treatment or prevention of COVID. In making that conclusion, it evaluated treatments that used invermectin or placebo in combination with standard care and whether treatment reduced death, illness, or the length of the infection.
Rapid detection, treatment of infections could avoid complications, additional surgeries after mastectomy
Many of those women opt to have their breasts surgically reconstructed, most commonly with implants, but a relatively high percentage develop infections after implant surgery, requiring intravenous antibiotics and often removal of the implant. This can lead to additional surgeries, delays in cancer care and increased costs, as well as added emotional distress for women already under strain from cancer diagnosis and treatment.
To address this problem, researchers at Washington University School of Medicine in St. Louis have developed a new tool to detect reconstruction-related infections early, before they cause symptoms. This method, reported in the Journal of Clinical Investigation, could allow for preemptive treatment that preserves implants, improves patient outcomes and reduces the psychological and financial burden on patients.
Led by Jeffrey P. Henderson, MD, PhD, a WashU Medicine professor, the study identified biomarkers of infection in fluid drained from reconstruction patients’ breasts days or even weeks before symptoms appeared. This represents a major opportunity for improvement over existing diagnostic methods, which rely heavily on clinical symptoms, such as redness and inflammation, that take time to appear and can overlap with normal reactions to surgery.
The findings are available online and will publish in print Feb. 16 in the Journal of Clinical Investigation.
“The ability to identify with a molecular signature early on that a patient will go on to have an infection opens up the possibility of surveillance as part of standard care,” Henderson said. “This has the potential to enable earlier treatment that would be far more effective – and potentially curative – in patients who would otherwise progress to prolonged courses of treatment and surgery, or even implant removal and reconstructive failure.”
Small molecules, big impact
The study originated when Henderson’s WashU Medicine colleague Margaret A. Olsen, PhD, a retired professor of medicine in the Division of Infectious Diseases who studies hospital infections, noticed high rates of infection among US patients who had reconstruction with implants after mastectomy. The discovery prompted Henderson and Olsen, a co-author on the study, to ask WashU Medicine plastic surgeons who performed breast reconstruction what they would need to improve outcomes in these patients. Their answer was simple: a clear yes/no test for infection.
To develop such a test, Henderson and lead author John A. Wildenthal, an MD/PhD student, leveraged their expertise in metabolomics, the study of metabolites that are created or broken down during cellular processes in the body. Metabolites can indicate the presence of an infection because they include byproducts of both the body’s response to pathogens and the metabolic activity of the pathogens themselves. By analysing changes in metabolite levels, scientists can identify patterns that are characteristic of infections, enabling early diagnosis.
Henderson and colleagues coordinated with WashU Medicine plastic surgeons to obtain fluid samples from 50 patient volunteers during several routine follow-up visits after surgery. The patients included women who later developed infections after post-mastectomy reconstruction and those who did not.
The researchers analysed the samples for differences between the two groups and identified metabolites that were significantly associated with infection and that appeared days to weeks before clinical signs and symptoms of infection. Further, they found that the presence of certain metabolites indicated more serious infections that might require more aggressive treatment.
“Originating from clinical intuition and validated through a clinical study, the evidence in this paper now supports proactive, targeted interventions to predict and address infections before they become clinically significant,” said Justin M. Sacks, MD, a co-author on the paper. “Such interventions can substantially reduce the burden of complications, implant loss and reconstructive failures in these patients.”
For instance, the findings could lead to the development of a point-of-care test that could be provided during a woman’s routine post-operative visits, noted co-author Terence M. Myckatyn, MD, a professor of surgery at WashU Medicine, who performs plastic and reconstructive surgery for breast cancer patients.
“If the test is positive, antibiotics can be started preemptively in these select patients to thwart infection,” Myckatyn said. “And perhaps just as important, we would not give antibiotics to those with a negative test, thereby adhering to a thoughtful approach for antibiotic stewardship.” Such careful use of antibiotics is important for preventing antibiotic resistance, he said.
In the near term, the team is planning additional studies to validate the results. Then a diagnostic tool could be developed and tested in clinical practice. In the future, the broader metabolomic findings about the development of tissue infection in humans could allow physicians to more selectively target a variety of post-surgical infections, for example, by revealing new drug targets.
“While better techniques are always being sought, the reality is that infections still occur despite a meticulous surgical approach,” said Myckatyn. “To be able to identify biomarkers that can portend an infection days before it develops is huge.”
Two bacteria working together to break down intestinal mucus are identified as a contributing factor to chronic constipation
Scientists at Nagoya University in Japan have found two gut bacteria working together that contribute to chronic constipation. The duo, Akkermansia muciniphila and Bacteroides thetaiotaomicron, destroy the intestinal mucus coating essential for keeping the colon lubricated and faeces hydrated. Their excess degradation leaves patients with dry, immobile stool. This discovery, published in Gut Microbes, finally explains why standard treatments often fail for millions of people with chronic constipation.
Notably, the study shows that Parkinson’s disease patients, who suffer from constipation decades before developing tremors, have higher levels of these mucus-degrading bacteria. While constipation in Parkinson’s disease has traditionally been attributed to nerve degradation, these findings suggest that bacterial activity also plays a crucial role in the development of their symptoms.
Why mucin matters for digestion
Constipation is a very common digestive problem. Doctors have assumed it happens because of slow gut movement when our intestines are not moving food along fast enough. However, this explanation does not work for everyone.
Some people have constipation with no identifiable cause, referred to as chronic idiopathic constipation (CIC). Parkinson’s disease patients also face severe, treatment-resistant constipation, though it is clinically categorized separately from CIC. Many struggle with severe constipation for 20 or 30 years before they develop tremors and movement problems, but researchers did not know why until now.
Instead of focusing on nerve and muscle movement in the gut, the researchers examined the protective gel-like coating called colonic mucin, a substance in the large intestine that lines the intestinal walls and is found within stool. Colonic mucin keeps stool moist, helps it move smoothly through our digestive tract, and protects the intestinal wall from bacteria.
They found that two gut bacteria work in sequence to break down this mucin. B. thetaiotaomicron uses enzymes to remove protective sulfate groups from the mucin, and A. muciniphila then breaks down and consumes the exposed mucin.
Sulfate groups attached to colonic mucin molecules normally prevent bacteria from degrading them. When too much mucin is destroyed, stool loses moisture and becomes hard and dry, causing constipation. Because the problem is mucin loss, not slow gut movement, standard laxatives and gut motility drugs are often ineffective.
Researchers have identified a two-step bacterial process driving a new type of constipation: one bacterium removes protective sulfate groups while another consumes the exposed colonic mucin. Credit: Tomonari Hamaguchi, Nagoya University
A new frontier for gut health treatment
“We genetically modified B. thetaiotaomicron so it could no longer activate the enzyme sulfatase that removes sulfate groups from mucin,” Tomonari Hamaguchi, lead author and lecturer from the Academic Research & Industry-Academia-Government Collaboration Office at Nagoya University explained.
“We put these modified bacteria into germ-free mice together with Akkermansia muciniphila, and surprisingly the mice did not develop constipation; the mucin stayed protected and intact.”
The experiment proved that blocking the sulfatase enzyme prevents the bacteria from degrading mucin. Therefore, drugs that block sulfatase could treat bacterial constipation in humans.
For millions of patients with treatment-resistant constipation, including those with Parkinson’s disease, this discovery offers hope for new therapies that address the root microbial causes of their condition.
Daily aspirin use does not offer a quick or reliable way to prevent colorectal cancer in the general population and carries immediate risks of serious bleeding, a new Cochrane review finds.
Colorectal cancer is one of the most common types of cancer worldwide. Prevention typically involves following a healthy lifestyle and periodically undergoing routine screening tests. In recent years, researchers have also explored the role of off-the-shelf medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), in reducing the incidence of colorectal cancer.
NSAIDs, which include ibuprofen and aspirin, are commonly used to reduce inflammation, fever, and pain. However, their role in the primary prevention of colorectal cancer remains uncertain and controversial.
Researchers from West China Hospital of Sichuan University in China analysed 10 randomised controlled trials including 124 837 participants, assessing whether aspirin or other NSAIDs could prevent colorectal cancer or precancerous polyps (adenomas) in people at average risk. The team found no suitable trials for non-aspirin NSAIDs, so their conclusions focus exclusively on aspirin.
Little to no short-term benefit and uncertain long-term effects
The review found that aspirin probably does not reduce the risk of colorectal cancer in the first 5 to 15 years of use. Possible protective effects after more than 10–15 years of follow-up were observed in some studies, but the certainty of this evidence is very low.
These potential long-term benefits come from observational follow-up phases of trials, in which participants may have stopped aspirin, started it independently, or begun other treatments, making the findings vulnerable to bias.
“While the idea of aspirin preventing bowel cancer in the long run is intriguing, our analysis shows that this benefit is not guaranteed and comes with immediate risks.”
— Dr Zhaolun Cai, lead author
Immediate and well-established risks
The findings also show clear evidence that daily use of aspirin increases the risk of serious extracranial haemorrhage and probably increases the risk of haemorrhagic stroke.
Although higher doses carry the greatest risk, low-dose (“baby”) aspirin also raises bleeding risk. Older adults and those with a history of ulcers or bleeding disorders may be particularly vulnerable.
The authors therefore caution that any potential long-term benefit must be weighed against the immediate and well-established risk of bleeding.
“My biggest worry is that people might assume that taking an aspirin today will protect them from cancer tomorrow. In reality, any potential preventive effect takes over a decade to appear, if it appears at all, while the bleeding risk begins immediately.”
— Dr Bo Zhang, senior author
Not a ‘one-size-fits-all’ solution
Previous evidence has shown potential benefits for people at high genetic risk of colorectal cancer, such as those with Lynch syndrome. However, this review focuses strictly on people at average risk, and the long-term evidence for them proved highly uncertain.
The authors urge that patients should not start taking aspirin for cancer prevention without a careful conversation with their healthcare professional about their personal risk of bleeding.
“This review reinforces that we must move away from a one-size-fits-all approach. Widespread aspirin use in the general population simply isn’t supported by the evidence. The future lies in precision prevention – using molecular markers and individual risk profiles to identify who might benefit most and who is most at risk.”
— Dr Dan Cao, senior author
The research team concludes that the story of aspirin for cancer prevention is far more complex than previously believed and that the balance of benefits and harms changes over time.
Dr Zhang adds:
“As scientists, we must follow the evidence where it leads. Our rigorous analysis of the highest-quality trials reveals that the ‘aspirin for cancer prevention’ story is more complex than a simple ‘yes or no.’ The current evidence does not support a blanket recommendation for aspirin use purely to prevent bowel cancer.”
