A new study from Karolinska Institutet challenges previous findings that suggested early surgery is more beneficial in the long term than medical treatment for patients with Crohn’s disease. The study replicates a Danish registry study using Swedish data and finds that the results are not comparable. The study was published in Clinical Gastroenterology and Hepatology.
A few years ago, a randomised controlled trial showed that early ileocecal resection – removal of the junction between the small and large intestine – could be a reasonable alternative to advanced drug therapy for patients with Crohn’s disease. This study gained significant attention and was widely discussed around the world. Recently, a Danish research group published a registry-based study in the journal Gastroenterology, concluding that real-world data showed that early ileocecal resection was clearly superior to medical treatment in the long term.
In the new Swedish study, researchers attempted to replicate the Danish study using nationwide Swedish registry data. They found that it is impossible to identify comparable populations in current observational data, as patients who underwent surgery or received medication during the study period differ according to existing treatment guidelines.
The Danish researchers made several design choices that further reduced the comparability between the groups. When the Swedish researchers applied the same definitions as the Danish study, they obtained similar results. However, when they used stricter definitions that more closely resembled the original randomized study, they no longer found a significant difference between the groups.
“We argue that the Danish study cannot be interpreted as proof that early surgery is better. That may very well be the case, but the data we currently have simply cannot answer that question,” says Ola Olén.
The developing brain of a two-week-old mouse pup under the microscope. The oxytocin system appears in green, the light-sensitive protein in red and cells that carry both show up in yellow. Cell nuclei are in blue. Credit: Weizmann Institute of Science
According to attachment theory, the attachment between an infant and a primary caregiver shapes the baby’s future social ties. Yet little is known about the biological mechanisms underlying childhood attachment, mainly because it is so difficult to study the young brain in natural conditions.
Now, scientists in Prof Ofer Yizhar’s laboratory at the Weizmann Institute of Science have developed a new, noninvasive research method that makes it possible to silence selected nerve cells deep within the brains of mouse pups without disrupting their natural behaviour. Using this method, the researchers investigated the role of oxytocin, a short protein released from nerve cells in the brain. While most oxytocin research has focused on adults, the new findings, published in Science, show that oxytocin also shapes the social behaviour of pups and may underlie emotional differences between males and females that emerge early in life.
Oxytocin, sometimes referred to as the “love hormone,” was once thought to simply promote sociability in adults. Over time, however, it became clear that its role is far more complex: In some circumstances, it intensifies behaviors and emotions far removed from love, such as anxiety or aggression. Recent research has also shown that young mammalian brains – including those of human children – are especially sensitive to oxytocin. In brain regions responsible for sensory processing, emotional regulation and social behavior, the number of oxytocin receptors peaks during early childhood: around ages two to three in humans, and two to three weeks in mice. Some studies have even linked oxytocin deficiency to childhood autism. Still, without sufficiently precise tools to examine neural activity deep within the developing brain, many aspects of the role of oxytocin in early life have remained a mystery.
“The findings may offer a clue as to why males and females diverge in their social behaviors and emotional worlds long before puberty”
To shed light on the subject, a team led by Dr Daniel Zelmanoff, a physician-scientist in Yizhar’s lab, developed a noninvasive technique to probe specific nerve cells in the young brain. The group, pioneers in the field of optogenetics – a technology that uses light to switch individual cells on or off – devised a method in which the targeted brain cells of mouse pups are infected with an engineered virus. This otherwise harmless virus introduces a foreign gene of mosquito origin that encodes a light-sensitive protein; when exposed to light, the protein “turns off” the nerve cell. In fact, the protein is so light-sensitive that the researchers could silence selected nerve cells deep inside the brain simply by shining red light on the pups’ heads.
“This new method allows us to peek inside the brain without disturbing the pups’ everyday lives, making it a powerful tool for studying nervous system development,” Yizhar explains. “It is especially useful for studying oxytocin because this hormone’s effects depend on social context – and our method lets us switch off the oxytocin system on demand, only during the exact situation we want to study.”
The researchers focused on oxytocin’s role during the temporary separation of a mouse pup from its mother and their reunion a few hours later – a situation familiar to every parent of a young child. The scientists observed increased oxytocin activity in the pup’s brain during separation, which returned to normal after reunion with the mother. Pups with an active oxytocin system during the separation gradually adapted to being alone in an unfamiliar environment, producing fewer ultrasonic vocalizations – the mouse equivalent of a baby’s cry. In contrast, pups whose oxytocin system was silenced did not adapt; they continued emitting distress calls at the same rate until reunited with their mothers. These findings show that the so-called “love hormone” also plays a critical role in coping with loneliness.
Attachment theory holds that children who are securely attached to their parents show distress when separated from them but are able to calm down over time, feeling free to explore their surroundings. “We discovered that mouse pups need an active oxytocin system in order to adapt to separation from their mothers,” says Yizhar. “This suggests that the oxytocin system plays a role not only in the brain of the parent, which was already known, but also in that of the infant. In addition, since oxytocin receptors are present in the sensory processing centers of the young brain, we hypothesize that this hormone also helps sharpen a pup’s senses when it is alone.”
Children do not quickly forget the experience of being separated from their parents, and this separation shapes how they behave when reunited. For example, a securely attached child separated from a parent for a few hours will seek contact upon reunion, and is quickly calmed. The researchers found that activation of the oxytocin system in mouse pups during separation not only strengthened them in the moment but also determined how they behaved when their mothers returned. These pups emitted more ultrasonic calls than usual, and the frequency of the calls grew as they got closer to their mothers. Using artificial intelligence, the team identified a distinct vocal pattern: Before attaching to the mother’s nipple, the pups made high-pitched, frequent calls; afterwards, their calls dropped in pitch and slowed in tempo.
“Activating the oxytocin system during separation increases the pup’s motivation to regain closeness to the mother when reunited,” Yizhar explains. “This is reflected in the heightened rate and unique pattern of their calls. We now understand that these ultrasonic vocalizations are much more than just crying: The high-pitched, rapid calls appear to signal a request for closeness, while the lower-pitched, slower-paced calls likely express a quick return to calm and a wish to remain attached. Of course, more research is needed to pin down the exact meaning of each vocalization type.”
In the next stage, the researchers explored whether oxytocin’s role in pups differs between the sexes, as it does in older animals. They found that female pups with an active oxytocin system emitted many more ultrasonic calls when reunited with their mothers than females with silenced oxytocin systems, whereas the calls of male pups were unaffected by the status of their oxytocin systems. “This is the first sex difference observed in oxytocin system activity at such an early stage of development,” Yizhar notes. “It may offer a clue as to why males and females diverge in their social behaviours and emotional worlds long before puberty.”
“Most known functions of oxytocin are shared by all mammals,” Yizhar concludes. “Still, future studies must check whether the hormone affects the development of social behaviour, emotional maturity and maternal attachment in the brains of children. If so, this could help us better understand what can go wrong in emotional and social development – as in autism spectrum disorder, for example – and how to intervene at an early stage.”
It is not only premature babies and children with underlying diseases who suffer from serious respiratory syncytial virus (RSV) infections. Even healthy, full-term babies are at significant risk of intensive care or prolonged hospitalisation – especially during the first three months of life. This is according to a comprehensive registry study from Karolinska Institutet published in The Lancet Regional Health – Europe.
RSV is a common cause of respiratory infections in young children and accounts for around 245,000 hospital admissions annually in Europe. Researchers have now analysed data from over 2.3 million children born in Sweden between 2001 and 2022 to find out who is at greatest risk of suffering serious complications or dying from an RSV infection.
Preventive treatment available
It is well-known that premature babies and children with chronic diseases are at increased risk of developing severe illness when infected with RSV. It is also known that children under three months of age are particularly vulnerable, but it has not been entirely clear how common severe disease is among previously healthy children. The study shows that the largest group among the children who needed intensive care or were hospitalised for a long period of time were under three months of age, previously healthy and born at full term.
“When shaping treatment strategies, it is important to take into account that even healthy infants can be severely affected by RSV,” says the study’s first author, Giulia Dallagiacoma, a physician and doctoral student at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “The good news is that there is now preventive treatment that can be given to newborns, and a vaccine that can be given to pregnant women.”
Starting September 10, 2025, all newborns in Sweden are being offered preventive treatment with antibodies during the RSV season. The drug works much like a vaccine and protects against severe RSV infection for about six months.
Several risk factors identified
A total of 1.7 per cent of the children in the study were diagnosed with RSV infection. Among those, just under 12 per cent (4,621 children) had a severe course of illness. The median age of children who needed intensive care was just under two months, and the majority of them had no underlying disease.
The researchers identified several factors that were linked to an increased risk of needing intensive care or dying. Children who were born in the winter, or had siblings aged 0–3 years or a twin, had approximately a threefold increased risk, while children who were small at birth had an almost fourfold increased risk. Children with underlying medical conditions had more than a fourfold increased risk of severe illness or death.
“We know that several underlying diseases increase the risk of severe RSV infection, and it is these children who have so far been targeted for protection with the preventive treatment that has been available,” says the study’s last author, Samuel Rhedin, resident physician at Sachs’ Children and Youth Hospital and associate professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “However, the study highlights that a large proportion of children who require intensive care due to their RSV infection were previously healthy. Now that better preventive medicines are available, it is therefore positive that the definition of risk groups is being broadened to offer protection during the RSV season to previously healthy infants as well.”
A Stanford University-led study has found that young children with attention deficit/hyperactivity disorder (ADHD) often receive medication just after being diagnosed, which contravenes treatment guidelines endorsed by the American Academy of Pediatrics.
The findings, from published JAMA Network Open, highlight a gap in medical care for 4- and 5-year-olds with ADHD. Treatment guidelines recommend that these young children and their families try six months of behaviour therapy before starting ADHD medication.
But paediatricians often prescribe medication immediately upon diagnosis, according to an analysis of medical records from nearly 10 000 young children with ADHD who received care in eight paediatric health networks in the United States.
“We found that many young children are being prescribed medications very soon after their diagnosis of ADHD is documented,” said the study’s lead author, Yair Bannett, MD, assistant professor of paediatrics. “That’s concerning, because we know starting ADHD treatment with a behavioural approach is beneficial; it has a big positive effect on the child as well as on the family.”
Medications not appropriate to under-6s
In addition, stimulant medications prescribed for the condition cause more side effects in young patients than they do in older children, Bannett said. Before age 6, children’s bodies don’t fully metabolise the drugs.
“We don’t have concerns about the toxicity of the medications for 4- and 5-year-olds, but we do know that there is a high likelihood of treatment failure, because many families decide the side effects outweigh the benefits,” he said. Stimulant medication can make young children more irritable, emotional, and aggressive.
ADHD is a developmental disorder characterised by hyperactivity, difficulty paying attention, and impulsive behaviour.
“It’s important to catch it early because we know these kids are at higher risk for having academic problems and not completing school,” Bannett said. Early identification and effective treatment for ADHD improve children’s academic performance. Research has shown that good treatment also helps prepare individuals with ADHD for many aspects of adulthood, such as maintaining employment, having successful relationships, and avoiding trouble with the law.
Complementary treatments
Behavioral therapy and medication, the two mainstays of ADHD treatment, have different purposes.
“Behavioral treatment works on the child’s surroundings: the parents’ actions and the routine the child has,” Bannett said. The therapy helps parents and kids build skills and establish habits compatible with how the child’s brain works.
The evidence-based behavioral treatment recommended by the American Academy of Pediatrics is called parent training in behavior management. The training helps parents build strong, positive relationships with their children; offers guidance in rewarding a child’s good behaviors and ignoring negative behaviors; and recommends tools that help kids with ADHD, such as making visual schedules to help them stay organized.
In contrast, medication relieves ADHD symptoms such as hyperactivity and inattentiveness, with effects that wear off as the body breaks down each dose of the drug.
Both approaches are needed for most kids with ADHD to do well. But previous studies of preschoolers diagnosed at age 4 or 5 show that it’s best to start with six months of behavioural treatment before prescribing any medication.
Rapid prescriptions
The researchers analysed data from electronic health records for children seen at primary care practices affiliated with eight US academic medical centres. They began with 712 478 records from children aged 3, 4, or 5 years old and were seen by their primary care physician at least twice, over a period of at least six months, between 2016 and 2023.
From these records, the scientists identified 9708 children who received an ADHD diagnosis, representing 1.4% of the children in the initial sample. They found that 42.2% were prescribed medication within a month of their ADHD diagnosis. Only 14.1% of children with ADHD first received medication more than six months after diagnosis. The researchers did not have access to data on referrals to behavioural therapy, but since young children are supposed to try the therapy alone for six months before receiving medication, any who were prescribed medication sooner were likely not being treated according to academy guidelines. A smaller study of recommendations for behaviour therapy, published in 2021, found only 11% of families got the therapy in line with guidelines.
Children who were initially given a formal diagnosis of ADHD were more likely to get medication within the first 30 days than those whose medical charts initially noted some ADHD symptoms, with a diagnosis at a later time. But even among preschoolers who did not initially meet full criteria for the condition, 22.9% received medication within 30 days.
Barriers to behavioural treatment?
Because the study was based on an analysis of electronic medical records, the researchers could not ask why physicians made the treatment decisions they did. But in informal conversations with physicians, outside the scope of the study, the researchers asked why they prescribed medication.
“One important point that always comes up is access to behavioural treatment,” Bannett said. Some locales have few or no therapists who offer the treatment, or patients’ insurance may not cover it. “Doctors tell us, ‘We don’t have anywhere to send these families for behavioural management training, so, weighing the benefits and risks, we think it’s better to give medication than not to offer any treatment at all.’”
Bannett said he hopes to educate primary care paediatricians on how to bridge this gap. For example, free or low-cost online resources are available for parents who want to learn principles of the behavioural approach.
And while the study focused on the youngest ADHD patients, behavioural management therapy also helps older children with the diagnosis.
“For kids six and above, the recommendation is both treatments, because behavioural therapy teaches the child and family long-term skills that will help them in life,” Bannett said. “Medication will not do that, so we never think of medication as the only solution for ADHD.”
A Swedish-led research team at Karolinska Institutet and Karolinska University Hospital has shown in a new randomised clinical trial that a low dose of the well-known medicine aspirin halves the risk of recurrence after surgery in patients with colon and rectal cancer with a certain type of genetic alteration in the tumour.
Every year, nearly two million people worldwide are diagnosed with colorectal cancer, and 20–40% develop metastases.
Previous observational studies have suggested that aspirin may reduce the risk of certain cancers and possibly also the risk of recurrence after surgery in patients with colorectal cancer harbouring mutations in genes within the PIK3 signaling pathway. These genes regulate key cellular processes such as growth and division. When mutated, these processes can become dysregulated, leading to uncontrolled cell proliferation and cancer development.
Randomised clinical trials were lacking
Prior findings have been inconsistent and no randomised clinical trials had previously confirmed the association. To address this gap, the ALASCCA trial was initiated, with the results now been published in The New England Journal of Medicine.
The current study included more than 3500 patients with colon and rectal cancer from 33 hospitals in Sweden, Norway, Denmark, and Finland. Patients whose tumours showed a specific genetic mutation in the PIK3 signalling pathway – a mutation found in approximately 40% of patients – were randomised to receive either 160mg of aspirin daily or a placebo for three years after surgery.
For patients with the genetic mutation in PIK3, the risk of recurrence was reduced by 55% in those who received aspirin compared with the placebo group.
“Aspirin is being tested here in a completely new context as a precision medicine treatment. This is a clear example of how we can use genetic information to personalise treatment and at the same time save both resources and suffering,” says first author Anna Martling, professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet, and senior consultant surgeon at Karolinska University Hospital.
Less favourable environment for cancer
So how does aspirin reduce the risk of recurrence of colon and rectal cancer? The researchers believe that the effect is likely due to aspirin acting through several parallel mechanisms – it reduces inflammation, inhibits platelet function and tumour growth. This combination makes the environment less favourable for cancer.
“Although we do not yet fully understand all the molecular links, the findings strongly support the biological rationale and suggest that the treatment may be particularly effective in genetically defined subgroups of patients,” says Anna Martling.
The researchers believe that the results could have global significance and influence treatment guidelines for colon and rectal cancer worldwide. Anna Martling sees the fact that the drug is well established as a major advantage.
“Aspirin is a drug that is readily available globally and extremely inexpensive compared to many modern cancer drugs, which is very positive,” says Anna Martling.
