A randomised trial from the Mass General Brigham Heart and Vascular Institute showed that a single 1000mg intravenous dose of ferric derisomaltose improved peak oxygen uptake and other functional measures at 12 weeks in patients with heart failure with preserved ejection fraction (HFpEF) and iron deficiency.
The IRON-MET HFpEF trial randomised 65 symptomatic participants (median age 68 years; 72% women; iron deficiency present in >50% of HFpEF overall) 2:1 to the iron infusion or placebo. Oral iron has previously proved ineffective in other heart-failure phenotypes, attributed to poor absorption. Results were presented at the 2026 American Heart Association Scientific Sessions and published simultaneously in Circulation.
At 12 weeks, peak VO₂ rose by approximately 10% in the iron arm and was unchanged with placebo. Pre-specified secondary endpoints (six-minute walk distance, VO₂ at the anaerobic threshold, and NYHA class) also improved, as did markers of iron bioavailability. Patient-reported health scores did not differ significantly. No serious adverse events were linked to the infusion.
Lead author Dr Gregory D. Lewis stated that the study was the first to comprehensively evaluate exercise responses to iron repletion in this population and that ferric derisomaltose improved multiple capacity measures. Dr Rajeev Malhotra noted that the peak VO₂ increment is clinically meaningful; longer-term outcome studies in more diverse cohorts are now required.
Around 7000 patients a year in Sweden who have not previously used opioids continue to collect their prescriptions several months after surgery, which increases the risk of dependence, a new doctoral thesis from Karolinska Institutet shows. The thesis also shows that the amount of opioids prescribed following major surgery can be reduced.
Opioids are effective medicines for severe pain following surgery, but prolonged use is associated with risks such as dependence and overdose. In his thesis, Claes Gedda at the Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, investigated how common it is for patients in Sweden to continue using opioids after surgery, which patients are at higher risk, and whether usage following major surgery can be reduced.
The largest study included 1 245 211 adults who underwent surgery in Sweden between 2018 and 2022 and who had not collected opioids for most of the year prior to their operation. Of these, 35 132 people, or 2.82%, continued to collect opioids both during the first 3 months and during months 4 to 6 after surgery.
”This corresponds to around 7000 patients per year in Sweden who collect opioids long after they should have recovered from surgery”, says Claes Gedda.
The risk was higher, for example, among older people and those with greater comorbidity, a recent cancer diagnosis, chronic pain, anxiety or depression, as well as alcohol or drug problems. Emergency surgery was also linked to a higher risk. Patients who collected opioids during the first week after surgery were more than twice as likely to still be collecting them several months later.
“Our results show that part of the risk can be identified even before surgery. At the same time, post-operative prescribing is a factor that the healthcare system can actually influence,” says Claes Gedda.
Different approach were used
In a study of 842 patients who underwent major colon and rectal surgery, an approach was used whereby opioids were administered on an as-needed basis rather than according to a fixed schedule, alongside other pain-relieving medicines. Over a four-year period, the median consumption of opioids fell by 70% and, towards the end of the study, almost one in three patients received no opioids at all during the first six days after surgery.
”This shows that it is possible to reduce the amount of opioids used after surgery. However, we do not yet know whether reduced early use also reduces the risk of long-term use. This needs to be investigated further,” says Claes Gedda.
The doctoral thesis was supervised by Mattias Soop at the Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet. The public defence will take place on 4 December 2026.
A doctoral thesis is the final written product of a postgraduate education, which in Sweden corresponds to four years of full-time studies. It varies between different disciplines how a doctoral thesis is structured. In the field of medicine, the doctoral student usually collects three to five scientific articles and presents them together with a thesis summary or overview, a so-called ‘kappa’ (literally meaning overcoat in Swedish). After the doctoral student has passed the public defence of the thesis, he or she receives a doctoral degree (also called a PhD), which is the highest possible educational degree in Sweden. Karolinska Institutet has approximately 2000 active doctoral students and each year approximately 350 doctoral theses are published at our university.
Cross sections of a whole mouse heart, following injection with the mRNA therapy. The areas glowing green mark cells that successfully took up the therapy, helping the scientists get a 3D view of where it can reach within the heart. Credit: Cambridge University
Scientists have developed a treatment that promotes the regeneration of damaged heart muscle following a heart attack, which has shown promising results in mice.
Since adult heart cells can’t repair themselves once damaged, this represents an important step towards a potential curative treatment for heart disease.
The treatment ‘reawakens’ heart muscle cells so they start to divide and help repair damaged muscle.
In a study in mice, this produced a stronger heartbeat and increased the amount of blood pumped through the heart with each heartbeat by around 10%, compared with mice that received a mock treatment, following a heart attack.
While this is not a full cure, even small improvements to heart function have been linked to lower mortality in patients and a better ability to carry out daily activities.
The treatment uses mRNA therapy to temporarily activate two proteins inside heart cells, called Myc and Cyclin T1, promoting repair of heart tissue.
This has the potential in future to be used to treat patients with heart failure. Around 200,000 people in the UK are diagnosed with heart failure each year and while current treatments can reduce symptoms and slow the progression of heart disease, they can’t regenerate heart muscle that has already been lost.
“These are really exciting results. There’s no cure for heart failure, and our treatment could potentially have a meaningful impact on the quality of life of millions of people around the world.”
Dr Catherine Wilson, Associate Professor at the University of Cambridge’s Department of Pharmacology and Gurdon Institute, co-senior author of the study.
Wilson added: “We’re not just treating the symptoms of heart failure – this approach could help the heart to repair itself.”
The team is now working to refine the treatment and has received funding from the British Heart Foundation to continue the work. Further trials in larger animal models, and then in humans, are needed to fully establish its safety and effectiveness.
Following a heart attack, the mRNA therapy was injected into the hearts of the mice and its effectiveness assessed by looking at the hearts with an echocardiogram – similar to looking at a baby inside the womb.
Since the treatment is short-lived and localised, it is not expected to cause any permanent modification to the heart cells – designed to reduce the risk of overgrowth, and no adverse effects were seen in the mice.
Reassessing the mice after 28 days and after 12 weeks showed that the improvement in heart function is long-lasting.
After a heart attack, an adult human heart can lose up to one billion heart muscle cells. Unlike many other organs in the body, the adult heart can’t regenerate itself, so lost cells are never replaced. Their loss reduces the strength of the heart and can lead to scar formation, heart failure and ultimately death.
As the world’s population grows and the prevalence of heart failure increases, the cost of patient care is anticipated to increase dramatically. The scientists believe that reawakening heart muscle cells in this way is a promising approach to treating heart failure patients.
Professor Bryan Williams, chief scientific and medical officer at the British Heart Foundation, said: “The heart is easily repaired when we are babies in the womb, but our heart muscle cells lose the ability to regenerate and fix the heart shortly after we are born. That makes it exciting when studies like this are able to reignite regeneration in heart muscle cells.
“Getting the human heart to repair itself is the holy grail for cardiologists.”
He added: “The gene therapy used by the researchers shows clear potential for heart patients. While the research is in mice, and still at an early stage, it is an important step forward towards therapies which could help repair the damage to the heart following a heart attack.”
This research was a collaboration between the University of Cambridge, QIMR Berghofer Medical Research Institute and AstraZeneca.
Skills training from Centurion to surgeons around the world
Photo by Natanael Melchor on Unsplash
Wednesday, 11 November 2026:A leading international specialist surgical training conference has once again invited veteran South African laparoscopic surgeon Professor Heine van der Walt to demonstrate his expertise on the global stage.
The Congress on Digestive System Surgery 2026, to be held on 12 and 13 November in Rome, has been described as ‘a congress built by surgeons for surgeons’ and Prof Van der Walt has demonstrated minimally invasive surgical procedures at this annual event for some 20 years. Last year, the Congress’s online streaming channels recorded over 12 million page views in addition to the 2000 healthcare professionals attending in person, illustrating the platform’s impact on surgeon training worldwide.
Professor Heine van der Walt
“This year, our team is performing a medley of procedures aimed at teaching foundational minimally invasive surgical techniques that are practically useful for the younger generation of surgeons to master,” says Prof Van der Walt, who will demonstrate laparoscopic techniques to delegates worldwide via video link from Netcare Unitas Hospital in Centurion.
Italian surgeon, Dr P.M. Maberti, recalls first meeting Prof Van der Walt while working in South Africa in various academic hospitals between 1985 and 1999, and the origins of the Congress. “I had the opportunity to appreciate his professionality, preparation, humanity and skill in other congresses during that period,” Dr Maberti says.
“Once back in Rome, I started collaborating with Prof Giorgio Palazzini again at the IIIth Surgical Institute of the Università La Sapienza, and Prof Palazzini had the idea of establishing the Congress on Digestive System Surgery aimed at fostering innovation and benefiting patients. Now in its 37th edition, the Congress is gaining increasing interest from the surgical community worldwide,” Dr Maberti says.
“It is now nearly two decades that Prof Van der Walt and his outstanding staff have participated in this Congress with maximum enthusiasm and skill, showing live surgery that is followed globally. The benefit is undoubted, especially for teaching young surgeons.”
Prof Van der Walt points out that the Congress has grown exponentially since communications technology enabled medical professionals to attend online, eliminating the time and expense of international travel, and widening access to the conference and the training opportunities it provides.
“I have been involved in demonstration surgeries for the international circuit since the early 1990s. I used to travel to all the different venues, operating in their hospitals with live local transmissions to the local congress venue. The transmissions started with four ISDN telephone lines, later we progressed to satellite transmissions and now 5G transmissions are negating much of the necessity for travel,” he says.
“Surgery can’t be learnt from textbooks alone. It demands practical technical skills and precision that surgeons largely pass down hand-to-hand from one generation to the next. Demonstrations such as these are a vital part of that process,” Prof Van der Walt says.
According to Dr Maberti, the great merits of the Congress are that procedures can be shared as if the delegates were in the operating theatre and the interaction it enables, which are essential for sharing surgical techniques globally.
“The Congress has become one of the largest surgical conferences, and it’s so popular because of the transfer of practical knowledge that takes place on this growing platform for the global digestive system medical community. Training is my vocation, and it is always rewarding to develop the skills that underpin better outcomes for patients,” Prof Van der Walt says.
Netcare Unitas Hospital general manager Pieter Louw congratulated Prof Van der Walt on his extensive contribution to sharing surgical expertise through live theatre demonstrations over many years.
“By taking fellow medical professionals through a procedure as it unfolds, Prof Van der Walt shares far more than technique. He offers insight into the clinical judgement, precision and decision-making that guide each stage of surgery.
“His continued dedication to training extends the value of his experience beyond the operating theatre, helping healthcare professionals in South Africa and around the world strengthen their skills and advance patient care in their own communities. Prof Van der Walt’s participation in this world congress underscores the calibre of minimally invasive surgical expertise available to patients at Netcare Unitas Hospital,” Louw concludes.
With El Niño conditions expected to bring a hotter, drier summer, Spotlight asks whether the KwaZulu-Natal government is ready to keep health services running and protect vulnerable communities during the extreme weather that may be on the way.
For Phumelele Shabalala, extreme weather has made an already difficult life harder.
The 46-year-old has lived in Vimbukhalo, a rural village near Bergville in KwaZulu-Natal’s Drakensberg foothills, for 24 years.
Shabalala grows vegetables to sell and help feed her four children. But during a dry spell in 2024, she says streams began drying up and her maize crops started dying.
Another resident in the area told Spotlight that they had lost cattle to dehydration and untreated wounds caused by sun exposure, threatening livelihoods dependent on farming.
In nearby Stulwane village, 28-year-old Nondumiso Nokwanda Sigubudu has experienced a different kind of devastation.
Heavy rainfall damaged her home in October 2025 and again in October this year, she says. Part of a wall remains open, exposing her family to the cold and leaving their home unsecured. Sigubudu believes the conditions have affected her two children’s health, saying they frequently suffer from colds and fevers.
Extreme weather can also make it difficult for residents to get medical care.
A mobile clinic visits Vimbukhalo once a month for check-ups and chronic medication refills. But Shabalala says it sometimes cannot reach the village when heavy rain makes roads impassable, leaving residents waiting for another visit or seeking alternative care.
Such disruptions are particularly concerning as El Niño, a natural climate pattern that can affect rainfall in southern Africa and increase the risk of drought, is forecast to strengthen towards the end of 2026.
KwaZulu-Natal has a long history of droughts and floods. According to a Council for Scientific and Industrial Research report, the province recorded 85 declared weather- and climate-related disasters between 2007 and 2021 — more than any other province.
For vulnerable communities in rural KwaZulu-Natal, this raises an urgent question: how prepared is the province to protect them and keep essential health services running when extreme weather strikes?
El Niño, KZN and what’s at stake
El Niño occurs when sea surface temperatures in the central and eastern tropical Pacific Ocean become unusually warm, disrupting atmospheric circulation and influencing weather patterns around the world.
South Africa’s seasonal outlook indicates an increased likelihood of below-normal rainfall across much of the country between December 2026 and February 2027, Dr Nosipho Zwane of the South African Weather Service said during a health department webinar in October.
But drought is not inevitable.
“El Niño is often associated with hotter and drier summer conditions. However, this does not happen exactly the same way every time,” Zwane said.
Speaking to Spotlight, University of Pretoria meteorology professor Willem Landman cautions that seasonal forecasts cannot predict individual storms or flash floods months ahead. Even a drier-than-average season can bring intense downpours and localised flooding.
Although El Niño is a natural phenomenon, its effects can be compounded by climate change. The World Meteorological Organization says there is no evidence that climate change is increasing the frequency or intensity of El Niño events, but a warmer atmosphere and ocean can amplify associated extremes, including heatwaves and heavy rainfall.
Hotter conditions increase the risks of heat exhaustion, heatstroke and worsening chronic illnesses, particularly among pregnant and postpartum women, young children, older people and outdoor workers, says public health specialist Celeste Madondo of the Foundation for Professional Development.
Research in rural KwaZulu-Natal has also linked heat exposure to adverse pregnancy outcomes. One study found a “clear relationship between maternal heat exposure during the month preceding conception and miscarriage”.
But the health risks of extreme heat are not always immediately apparent.
“The difficulty with heat is that you can’t see it. You can feel it, but you can’t necessarily see its effects,” Madondo says. “With droughts and floods, the damage is visible. You can see the flooding. You can see that your house is gone.”
Dam levels versus rural realities
While extreme heat poses health risks of its own, reduced rainfall can also threaten the water supplies and livelihoods that rural communities depend on.
South Africa’s major dams were 97.7% full on average in October, compared with 88.3% in KwaZulu-Natal. But Landman says these figures do not necessarily reflect water availability in rural communities dependent on streams, boreholes and rainfall.
For farming households, less water can mean fewer crops, livestock losses and reduced income. As Landman puts it: “If you don’t plant, you don’t have food.”
Drought can also make it harder for people to stay on HIV treatment. In KwaZulu-Natal, almost 1.6 million people were receiving antiretroviral treatment in 2025, according to Thembisa, the leading mathematical model of HIV in South Africa.
Research by the Africa Health Research Institute (AHRI) examined the impact of drought on HIV treatment in rural KwaZulu-Natal, analysing records from more than 40 000 people at 17 clinics between 2010 and 2018. The study found that drought was associated with fewer patients taking their medication as prescribed or staying in HIV care, with some recovery after the drought.
A related study, based on interviews with 27 people living with HIV in rural Hlabisa, in the uMkhanyakude district, explored how the 2015–2016 El Niño-related drought affected access to treatment.
Collins Iwuji, a professor of climate, environment and health at AHRI and co-author of both studies, says food insecurity was among the challenges patients faced.
“During the drought, the price of food was also going up and they didn’t want to take their pills on an empty stomach, because of the potential side effects,” Iwuji explains. “So what some of them did was they skipped the pill.”
Others missed clinic appointments while collecting water or lost contact with their usual clinics after moving with their livestock in search of water.
Iwuji cautions that their work could not prove that drought caused these treatment interruptions, although participants’ accounts suggested that drought-related hardship played a role.
Asked whether the province’s HIV services are now better prepared for climate-related disruptions, Iwuji says improvements have been “partial rather than systematic”.
Measures such as allowing people living with HIV to collect three to six months of medicines at a time and community medicine collection points can reduce the need for frequent clinic visits. But Iwuji says these services expanded significantly during the COVID-19 pandemic, rather than in response to climate-related emergencies.
Is KZN ready?
The question of preparedness extends beyond HIV services. The devastating floods of April and May 2022 exposed serious problems within the province’s preparedness for extreme weather.
The Presidential Climate Commission described the government’s response as largely reactive, identifying poor coordination between departments, inadequate preparation, and gaps in getting early warnings to vulnerable communities.
Problems were also evident within the health system. A 2026 study involving staff at a KwaZulu-Natal provincial tertiary hospital found that the facility lacked specific plans for weather-related emergencies when researchers collected data in 2023. Staff also reported shortages of personnel and resources, difficulties obtaining emergency supplies and poor communication.
Despite these efforts, a draft health-sector readiness assessment presented by the national health department’s Director of Epidemiology and Surveillance, Mbhekiseni Khumalo, at a webinar in October suggests significant gaps remain.
The country scored 61% across 11 areas of preparedness. Rapid response teams and communication with communities lagged at 45%, while coordination received just 28%. Health service delivery performed better at 82%. The assessment reflects preparedness nationally rather than in KwaZulu-Natal specifically. The findings are preliminary, with supporting evidence attached for only 10% of the indicators assessed.
In KwaZulu-Natal, the provincial health department says it has put measures in place to prepare for extreme weather emergencies.
“The department receives weather warnings through the Provincial Disaster Management Centre, the South African Weather Service application and the National PHEOC WhatsApp channel,” says provincial department spokesperson Ntokozo Maphisa.
This information is then shared with all district health emergency teams, which then put response measures into action.
Maphisa says the department has also developed backup plans for floods, heatwaves, fires and other emergencies, with instructions for healthcare workers. The department also works with other sectors to maintain essential health services, according to Maphisa.
From weather warnings to action
One challenge is ensuring that weather warnings reach healthcare facilities and communities in time for them to act.
A R46.5-million WEATHER project, involving the University of KwaZulu-Natal and international partners, aims to improve how flood notifications reach clinics and hospitals.
“Published research has already shown that official warnings did not reach some eThekwini community health centre managers in 2022. Closing that gap between warning and facility action is at the centre of the system we are designing,” says one of the project’s principal investigators, Professor Saloshni Naidoo.
The research also found that the centres’ emergency plans lacked clear instructions for responding to weather-related disruptions.
Naidoo explains that the proposed system would combine official weather warnings with practical advice for health workers, such as checking medicine supplies and contacting patients on chronic treatment. These aspects of the system still need to be developed with the provincial health department.
The system is being designed to reach rural communities with poor internet connectivity.
Maphisa confirms that senior provincial health managers are involved in the project, which is expected to be tested in early 2027 and evaluated later that year. It will therefore not be operational during the coming summer.
Can hospitals and clinics withstand the next disaster?
The condition of clinic and hospital buildings is another important part of preparing for extreme weather.
The provincial health department has been repairing facilities damaged by severe storms, including the 2022 floods.
Its Strategic Plan 2025/26–2029/30 lists 47 repair projects involving roofs, gutters and drainage systems. At the time of the plan, four were complete, 19 under construction, 18 at the tender stage and six still being planned.
But repairing damage does not necessarily make facilities more resilient to future extreme weather.
The Presidential Climate Commission has warned that rebuilding damaged infrastructure without making it better able to withstand extreme weather could leave it vulnerable to future disasters.
Iwuji says making healthcare facilities more resilient starts with assessing the risks each building faces.
He says the WHO has developed a framework for assessing facilities’ vulnerability to floods, storms, extreme heat and drought, as well as their capacity to cope with these threats. Such assessments can help determine what improvements each facility needs.
Extreme heat presents another challenge, particularly in ageing healthcare buildings.
“The buildings are old. The aircons don’t work. It’s not maintained,” Iwuji says. “Now if you have an overcrowded facility that’s hot, the healthcare workers are also experiencing the effects of the heat. But we expect them to ensure that they serve clients to the best of their ability under these conditions.”
The KwaZulu-Natal health department did not answer Spotlight’s questions about whether the repairs include measures to make healthcare facilities more resilient to future extreme weather.
Iwuji acknowledges that the province has made progress in improving coordination between departments since the 2022 floods, but questions how far these changes have translated into action. “There is movement towards creating some resilience. But in terms of practical implementation and what that means, that is what I haven’t seen yet,” he says.
The U.S. Food and Drug Administration is requiring manufacturers of all glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to add information about a potential increased risk of non-arteritic anterior ischaemic optic neuropathy (NAION) to the Warnings and Precautions section of product labelling.
NAION is a rare condition that can produce acute, painless vision loss in one eye, including permanent impairment, the agency said in a drug safety communication issued November 9, 2026. Cases have been reported with every currently marketed GLP-1 RA.
Key Takeaways
FDA is requiring a class-wide Warnings and Precautions labelling change for GLP-1 RAs to note a potential increased risk of NAION.
In an FDA meta-analysis of 126 randomised trials, the NAION incidence was 6.4 events per 100 000 person-years with GLP-1 RAs versus 3.8 with placebo or non-GLP-1 glucose-lowering drugs.
Clinicians should counsel patients to report sudden painless monocular vision changes immediately and refer suspected cases promptly to ophthalmology; discontinuation should be considered unless benefits clearly outweigh risks.
The agency is requiring application holders for all GLP-1 RA medications to add information to the Warnings and Precautions section of labelling about the potential increased risk of NAION associated with use of these medications,” the FDA stated. NAION results from reduced blood flow to the optic disc; its precise pathophysiology is incompletely understood. Established risk factors include smoking, diabetes, hypertension, sleep apnoea, anaemia, and kidney disease. Occurrence in one eye elevates the risk of involvement of the fellow eye.
Symptoms typically include sudden, painless vision loss in one eye (often noticed on waking), visual-field defects such as blind spots or tunnel vision, colour distortion, and reduced central acuity. Patients should seek medical attention immediately if these occur. Individuals with a prior NAION event should discuss with their clinician whether to continue or stop the GLP-1 RA.
The agency examined clinical-trial data, animal studies, postmarketing reports, and observational analyses. A meta-analysis of 126 trials encompassing 134 253 patients (78 217 treated with a GLP-1 RA) and nearly 289 000 person-years of exposure identified 15 probable NAION events – 10 among GLP-1 RA recipients and 5 among those receiving placebo (none among recipients of other non-GLP-1 glucose-lowering agents). This yielded the 6.4 versus 3.8 per 100 000 person-years rates noted above. Background incidence in adults older than 50 years is estimated at 2.3 to 10.2 cases per 100 000p-y.
Europe’s drug regulator warned about the risk 17 months ago.
A separate FDA retrospective cohort analysis in adults with type 2 diabetes found no statistically significant increase in NAION risk with GLP-1 RAs versus SGLT-2 inhibitors, but a higher risk versus DPP-4 inhibitors. Animal data did not reveal a clear mechanism. The absolute risk remains low, and the FDA characterised the finding as a potential association rather than a confirmed causal relationship.
GLP-1 RAs (including semaglutide, tirzepatide, liraglutide, dulaglutide, and others) are approved for type 2 diabetes, chronic weight management, and selected cardiovascular, renal, and other indications. The labelling change applies across the class, including dual GIP/GLP-1 agonists and the oral agent orforglipron.
NAION presents as acute, painless monocular vision loss, often noticed upon awakening, with an altitudinal or other visual-field defect and a relative afferent pupillary defect. Fundoscopy typically shows disc oedema in the acute phase, followed by pallor. There is no established acute treatment that restores vision; management focuses on secondary prevention (control of vascular risk factors, smoking cessation) and counselling about the roughly 15–25% risk of sequential involvement of the fellow eye over subsequent years. Prompt ophthalmology or neuro-ophthalmology referral is essential both to confirm the diagnosis and to exclude arteritic causes (giant-cell arteritis), which require urgent systemic corticosteroids. In the GLP-1 RA context, shared decision-making about drug continuation should weigh the substantial cardiometabolic benefits against the small absolute increment in this rare event, particularly in patients with preexisting optic-nerve risk factors.
Healthcare professionals are advised to instruct patients to report sudden monocular visual changes immediately, refer suspected cases urgently, and consider discontinuing the GLP-1 RA unless treatment benefits clearly outweigh the risk.
An international trial found that adding two medicines to treatment around bladder-removal surgery improved survival for people who could not receive, or chose not to have, cisplatin chemotherapy.
An estimated 78 in every 100 people receiving the drug combination were alive two years after joining the VOLGA trial, compared with 69 in every 100 in the comparison group who were offered surgery without the trial medicines. The findings could expand treatment options for people unable to receive cisplatin chemotherapy, potentially providing an option to receive less drug treatment after surgery than some other approaches.
The trial, led by Professor Thomas Powles, involved people whose cancer had grown into the bladder’s muscle wall. It tested two medicines: durvalumab, which helps the immune system respond to cancer, and enfortumab vedotin, which uses an antibody to deliver a cell-killing drug.
The findings were published in the New England Journal of Medicine and announced at ESMO 2026. The study was sponsored by AstraZeneca.
Why are more treatment options needed?
Cancer that has grown into the bladder’s muscle wall is called muscle-invasive bladder cancer. If it has not spread to distant organs, surgery or radiotherapy can be used to remove or destroy the cancer, potentially preventing it from returning.
Removing the bladder is one treatment option. But even after surgery, cancer can return if microscopic cancer cells remain elsewhere in the body. Chemotherapy containing cisplatin can improve survival when given before surgery. However, kidney problems, hearing loss or other health conditions can make it unsuitable for some people.
Recent trials have expanded the options for people with bladder cancer. For people who can receive cisplatin, adding durvalumab to chemotherapy before surgery, then continuing durvalumab afterwards, improves survival. NICE, which assesses treatments for NHS use, recommends this approach.
Another combination, pembrolizumab and enfortumab vedotin, has also improved survival in trials, including among people unable to receive cisplatin. In the KEYNOTE-905 trial involving these patients, both medicines were given before and after surgery. Enfortumab was given for nine treatment cycles: three before surgery and six afterwards.
VOLGA tested a different approach: giving just three cycles of enfortumab, all before surgery, with durvalumab before and afterwards. Researchers wanted to see whether this could improve survival while avoiding the need to give enfortumab during recovery from major surgery.
What did the treatment involve?
The trial involved 695 people across 25 countries who could not receive cisplatin or had chosen not to have it. They were assigned by chance to three groups.
One group was offered durvalumab and enfortumab before surgery, followed by durvalumab afterwards. A second was offered the same medicines plus another immunotherapy, tremelimumab. The comparison group was offered surgery without these trial medicines, but could receive other approved medicines afterwards.
What were the benefits and risks?
The survival improvement with durvalumab and enfortumab – 78 versus 69 people in every 100 alive at two years – was statistically significant. The combination also improved ‘event-free survival’, which measured how long people lived without their cancer progressing or returning. It also counted not undergoing planned bladder-removal surgery while cancer remained as an event, whether this was because of worsening health or a decision not to proceed. At two years, an estimated 64 in every 100 were alive without a recorded event, compared with 45 in every 100 in the comparison group.
The tremelimumab combination improved event-free survival, but did not show a statistically significant overall survival benefit at this analysis.
The survival benefit came with additional risks compared with surgery without the trial medicines. Health problems classified as severe or worse occurred in about 71 in every 100 receiving durvalumab and enfortumab, compared with 50 in every 100 in the comparison group. These included problems from any cause, not all of which were caused by the medicines. One death was considered treatment-related in the durvalumab–enfortumab group, and five in the group also receiving tremelimumab.
What happens next?
Researchers will continue following participants to understand how long the survival benefit lasts and assess longer-term effects of treatment.
VOLGA showed that durvalumab with enfortumab helped people live longer than those offered surgery without the trial medicines. However, it did not compare this combination directly with pembrolizumab and enfortumab, which improved survival in the recent KEYNOTE-905 trial. Therefore, the findings cannot tell doctors which approach offers the best balance of survival and side-effects for patients. Further trials could answer this question and establish who needs enfortumab after surgery and who could safely have less treatment.
Before the VOLGA combination can become a routine NHS option, it requires regulatory approval, which will consider the benefits and risks.
VOLGA adds to recent progress in bladder cancer treatment, providing evidence for another option for people who cannot receive cisplatin chemotherapy. This growing range of approaches gives researchers more opportunities to find treatments that help people live longer while limiting side effects and the demands of treatment.
Previous research has raised hopes that aspirin might reduce the risk of colorectal cancer returning after treatment. However, a large randomised clinical trial has found no such benefit for patients who had surgery for colorectal cancer that had spread to the liver.
Colorectal cancer is one of the most common cancers in Norway, which also has one of the highest incidence rates in the world. Approximately 30% of patients with colorectal cancer develop liver metastases during the course of their disease. Once the disease has spread, it is much more difficult to treat than primary colorectal cancer confined to the bowel.
“Patients rarely die from the primary tumour itself. It is the metastatic disease that is usually life-threatening,” says Sheraz Yaqub, Professor at the University of Oslo and consultant hepatobiliary surgeon at Oslo University Hospital.
For many patients, surgery offers the best chance of a cure.
“But even when we remove the tumours surgically, the cancer returns in more than half of patients,” says Yaqub.
Previous studies have suggested a protective effect of aspirin
Previous observational studies have suggested that aspirin use after colorectal cancer treatment may be associated with a lower risk of recurrence and improved survival. More recent randomised trials have investigated whether aspirin can provide such benefits, particularly in patients with specific molecular alterations in their tumours.
Yaqub and his colleagues wanted to find out whether aspirin could have the same preventive effect in patients whose colorectal cancer had spread to the liver.
“We wanted to know whether we could prevent the cancer from returning by giving aspirin to these patients as well,” Yaqub says.
Aspirin has long been used to treat pain, fever and inflammation.Its potential to prevent cancer recurrence has therefore attracted considerable interest.
“Aspirin is inexpensive, widely available and has been used for more than a century. Its effects and side effects are well known, which made it an attractive candidate for preventing cancer recurrence,” says Yaqub.
Could aspirin prevent recurrence after treatment for liver metastases?
The researchers conducted ASAC, a randomised, double-blind, placebo-controlled trial investigating whether aspirin could reduce the risk of recurrence after curative-intent treatment of colorectal cancer liver metastases.
A total of 466 patients were randomised at 14 hospitals in Norway, Sweden and Denmark. All had undergone treatment (surgery or local ablation) for colorectal cancer liver metastases.
The participants were randomly assigned to receive either aspirin 160mg daily or an identical placebo for up to three years.
“For most patients, the cancer returns within the first two years after surgery. That is why we followed participants for three years,” says Yaqub.
No reduction in recurrence with aspirin
The researchers found that aspirin did not reduce the risk of the cancer returning, compared with placebo. Patients who received aspirin also had a lower overall survival rate, but this finding should be interpreted with caution. Serious adverse events were more common in the aspirin group.
“We found no benefit from aspirin in preventing cancer recurrence in these patients. The finding of lower overall survival, together with higher frequency of serious adverse events also raise concerns,” says Yaqub.
“Our results show that aspirin should not be routinely recommended to prevent recurrence after curative-intent treatment of colorectal cancer liver metastases,” he adds.
Why randomised trials matter
In an earlier study, Yaqub and colleagues linked information from the Norwegian Cancer Registry and the Norwegian Prescription Database. That registry-based study suggested that patients with colorectal cancer who were taking aspirin lived longer than those who were not.
However, studies based on health registries cannot show with certainty whether a treatment was the reason for the difference.
“Registry studies can identify associations, but they cannot establish whether aspirin itself is responsible for improved survival. Randomised, placebo-controlled trials provide much stronger evidence about the effects of treatment,” he explains.
Why might aspirin benefit some patients but not others?
The reasons are not yet clear, but differences in disease stage and tumour biology may play a role.
The ASAC trial was conducted alongside the Scandinavian ALASCCA trial. Both studies examined molecular changes in tumour tissue.
The ALASCCA study found that aspirin reduced recurrence in some patients with localised colorectal cancer whose tumours carried specific alterations in the PI3K signalling pathway. In contrast, the ASAC trial found no benefit for patients who had been treated for colorectal cancer that had spread to the liver, including those with the molecular alterations examined in the study.
“What works for one group of patients does not necessarily work for another. We cannot simply transfer results from patients with primary colorectal cancer to patients who have been treated for liver metastases,” says Yaqub.
Patients should not stop taking aspirin without medical advice
The ASAC trial investigated the effect of starting aspirin after cancer treatment. Patients who were already taking aspirin were not eligible to take part.
The findings therefore do not mean that people who already take aspirin for other medical reasons should stop treatment.
“Patients who are already taking aspirin for cardiovascular disease or other medical indications should not stop treatment because of these findings. Any changes should be discussed with their treating physician,” Yaqub says.
A study led by Queen Mary University of London has found that a new treatment could offer a lasting cure for some people with a common hormonal cause of high blood pressure, even after they stop taking medication. The treatment, known as extended aldosterone synthase inhibition (EASI), involves taking a new class of drugs for 6-12 months to target excess production of the hormone aldosterone, a common cause of high blood pressure.
Unlike conventional treatments that control blood pressure, the EASI-treatment appears to reverse its underlying cause, removing the need for lifelong medication. Until now, cure has required surgery to remove an entire adrenal gland.
The study, published in the New England Journal of Medicine, followed 14 people treated at eight centres across the United States. Researchers found that the EASI-treatment led to sustained reversal of excess aldosterone production and partial or complete resolution of high blood pressure for up to two years after treatment ended.
Hormone levels and blood pressure remained similar to, or lower than, those recorded during their EASI treatment, suggesting that the benefits could persist long after people stop taking the drug. The findings raise the possibility that, for some people, high blood pressure could be cured rather than managed with lifelong medication.
Figure 1: The graphs compare blood pressure and hormone measurements before treatment with those at 6 months, 1 year and 2 years after stopping an extended course of aldosterone synthase inhibition. The large reduction in aldosterone-to-renin ratio is due to a fall in the adrenal gland hormone, aldosterone, and compensatory increase in the kidney hormone, renin. The third row shows apparent safety of the treatment, with only modest increases in blood potassium and creatinine – a marker of kidney function.
It is estimated that between 5–10% of hypertension cases are caused by primary aldosteronism, a condition in which benign nodules in the adrenal glands produce too much aldosterone. This causes the kidneys to retain excess salt, raising blood pressure.
The scientific basis for EASI-treatment dates back to a 2005 experiment in mice, which showed that deleting the gene responsible for producing aldosterone synthase caused the cells that make aldosterone to disappear. Researchers at Queen Mary predicted that prolonged treatment with an aldosterone synthase inhibitor might have a similar effect in humans, potentially removing the underlying cause of their hypertension.
The opportunity to investigate this came through the first study of this class of drugs in people with primary aldosteronism, reported last year in the New England Journal of Medicine, in a paper also led by Queen Mary.
Researchers subsequently examined routine follow-up measurements of people’s blood pressure and hormone levels, comparing them with values recorded before EASI treatment. They found that the main marker of excess aldosterone production remained 99 per cent lower than before treatment, while blood pressure was, on average 25 points lower. Almost a quarter of those who participated had normal blood pressure without taking any other medication.
Although aldosterone synthase inhibitors have previously been tested in larger studies of people with hypertension, these generally involved shorter treatment periods of 6–12 weeks, with outcomes measured during treatment. In contrast, the new Queen Mary-led study found that the benefits of 6–12 months of treatment persisted for up to two years after treatment had ended.
Morris Brown, lead author and Professor of Endocrine Hypertension at Queen Mary, said: “While duly cautious about our findings because of the pragmatic nature of the study, they were predicted by previous experiments, and longer follow-up may justify a claim that a finite course of medication leads to infinite cure.
“EASI-treatment is unlikely to be the elixir for most patients with hypertension. But the possibility of tablets achieving a surgical cure has long been a holy grail for this common type of hypertension.”
Mason Freeman, Professor of Medicine at Harvard Medical School and initiator of the original study while medical director at Cincor, said “This follow up study led by Dr Brown has generated some extraordinary and unexpected findings. The sustained remission in the biochemical markers of the hyperaldosterone state, combined with much improved blood pressure levels, offers the very exciting possibility that many patients with primary aldosteronism may be able to be treated with a once a day pill, perhaps for a limited period of time, and obtain similar benefits to what we now achieve only after invasive diagnostic testing and major adrenal surgery.”
Building on these findings, the researchers are now leading a larger prospective clinical trial called ELIXIR to investigate whether the EASI treatment can provide a lasting cure for people with primary aldosteronism. The trial will also use molecular imaging of the adrenal glands to investigate whether prolonged treatment causes aldosterone-producing cells to disappear.
Dietary potassium restriction is important for managing hyperkalaemia, or high blood potassium levels, in individuals on maintenance haemodialysis, but it imposes a substantial day-to-day burden. Results from a recent clinical trial indicate that adding the potassium binder sodium zirconium cyclosilicate (SZC) may help. The findings were published in BMC Nephrology and also presented at American Society of Nephrology (ASN) Kidney Week 2026 October 22–25.
In the multicentre, randomised, open-label, parallel-group trial, outpatients receiving thrice-weekly maintenance haemodialysis with pre-dialysis serum potassium of 5.5 to < 6.5 mEq/L were assigned to SZC plus standardised nutritional counselling or nutritional counselling alone for 8 weeks.
In the main analysis including 183 patients, those who received SZC plus standardised nutrition counselling had a greater improvement in quality of life related to dietary potassium restriction than those who received nutrition counselling alone. SZC also lowered pre-dialysis serum potassium more effectively. No patient in the SZC group needed rescue treatment during the 8-week study, compared with 25 of 92 patients in the control group. In exploratory analyses, the investigators also saw an increase in fruit intake without an increase in total dietary potassium intake, as well as improvements in several areas of kidney disease-related quality of life. There were no serious treatment-related adverse events or deaths.
“SZC may provide an important patient-centred benefit beyond lowering serum potassium. When added to standardised nutritional counselling and regular potassium monitoring, SZC reduced the day-to-day burden of dietary potassium restriction while also providing better potassium control,” said corresponding author Hiromichi Wakui, MD, PhD, of Yokohama City University Graduate School of Medicine. “Hyperkalaemia treatment should be judged not only by whether the potassium level falls, but also by whether treatment makes daily life less burdensome for patients.”
The investigators stressed that individualised dietary assessment, regular potassium monitoring, and attention to overall nutritional quality remain essential. When dietary restriction alone places a substantial burden on patients, potassium-binding therapy may support a safer and more patient-cantered management strategy.”
