Author: ModernMedia

Categories : Metabolic DisordersTags :

Most Obesity Drugs Do Not Improve Quality of Life or Heart Health

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Treatment decisions should be individualised, balancing expected benefits, harms, treatment burden, costs, availability, and patient preferences, say researchers

By HualinXMN – Own work, CC BY-SA 4.0

Despite substantial weight loss, most obesity drugs such as Wegovy and Mounjaro do not meaningfully improve quality of life and few show cardiovascular benefits at one year, finds an analysis of the latest evidence published by The BMJ today.

More weight loss is also generally accompanied by greater harms including stomach and bowel symptoms, fatigue, and loss of lean (muscle) mass – and improvements are not sustained after stopping treatment.

Several drugs for adults with overweight or obesity produce substantial weight loss, but most have not been compared directly in head-to-head trials, leaving uncertainty about the broader balance of benefits and harms.

To address this, researchers searched scientific databases for randomised controlled trials comparing one or more drugs with lifestyle changes, placebo, or another drug.

They found 262 eligible trials involving 99,791 participants (average age 49; 63% female; average BMI 35) that evaluated 19 currently available and emerging obesity drugs with follow-up from 12 to 172 weeks.

Benefits included changes in body weight, fat mass, and quality of life, while potential harms included changes in lean mass, gastrointestinal adverse events, gallbladder related disorders and fatigue.

The trials were of varying quality, but the researchers were able to assess the certainty of evidence using the recognised GRADE system.

Compared with lifestyle changes alone, the largest weight loss after one year was with tirzepatide (14.9%) and CagriSema (14.8%), followed by oral semaglutide (10.9%), orforglipron (9.9%), subcutaneous semaglutide (9.8%), and phentermine-topiramate (8.1%).

Emerging drugs – including retatrutide, ecnoglutide, and mazdutide – showed large effects on weight loss but are supported by low or very low certainty evidence.

Greater weight loss was consistently accompanied by higher rates of side effects and treatment discontinuation, which the authors say indicates a clear benefit-harm trade-off.

Tirzepatide reduced fat mass the most (by 25.7%) but also lean mass the most (8.3%). Subcutaneous semaglutide was the only drug associated with a reduced risk of death from any cause (19%), heart attack (28%), and heart failure (57%). Tirzepatide also reduced heart failure risk by 51%.

No drug convincingly reduced kidney failure or showed clinically important improvements in quality of life.

The authors acknowledge that most trials had relatively short follow-up, limiting conclusions about long term safety, quality of life, and effects on heart and kidney health. In addition, evidence for several newer drugs was sparse and of low certainty, and trial populations may not fully represent real world patients.

However, they say this review provides a comprehensive and up-to-date comparison of currently available and emerging obesity drugs across a broad set of outcomes important to patients, clinicians, and policymakers.

They conclude: “Treatment decisions for obesity should be individualised, balancing expected benefits, harms, treatment burden, costs, availability, and patient preferences.”

This study represents an important step in providing comparative information to inform patient-clinician discussions about obesity drugs in this rapidly evolving landscape of treatment options, say researchers in a linked editorial.

And they suggest future studies that incorporate individual characteristics, as well as long term outcomes, such as mortality, should provide additional data to inform individualised decision making.

Source: The BMJ Group

Categories : Ageing Diet and NutritionTags :

Are Meat Eaters Really More Likely to Live to 100 than Non‑meat Eaters, as a Recent Study Suggests?

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Photo by Jose Ignacio Pompe on Unsplash

Chloe Casey, Bournemouth University

People who don’t eat meat may be less likely than meat eaters to reach the age of 100, according to a recent study. But before you reconsider your plant-based diet, there’s more to these findings than meets the eye.

The research tracked over 5,000 Chinese adults aged 80 and older who participated in the Chinese Longitudinal Healthy Longevity Survey, a nationally representative study that began in 1998. By 2018, those following diets that don’t contain meat were less likely to become centenarians compared with meat eaters.

On the surface, this appears to contradict decades of research showing that plant-based diets are good for your health. Vegetarian diets, for example, have been consistently linked to lower risks of heart disease and stroke, type 2 diabetes and obesity. These benefits come partly from higher fibre intake and lower saturated fat consumption.

So what’s going on? Before drawing any firm conclusions, there are several important factors to consider.

Your body’s needs change as you age

This study focused on adults aged 80 and older, whose nutritional needs differ markedly from those of younger people. As we age, physiological changes alter both how much we eat and what nutrients we need. Energy expenditure drops, while muscle mass, bone density and appetite often decline. These shifts increase the risk of malnutrition and frailty.

Most evidence for the health benefits of diets that exclude meat comes from studies of younger adults rather than frail older populations. Some research suggests older non-meat eaters face a higher risk of fractures due to lower calcium and protein intake.

In later life, nutritional priorities shift. Rather than focusing on preventing long-term diseases, the goal becomes maintaining muscle mass, preventing weight loss and ensuring every mouthful delivers plenty of nutrients.

The study’s findings may, therefore, reflect the nutritional challenges of advanced age, rather than any inherent problems with plant-based diets. Crucially, this doesn’t diminish the well-established health benefits of these diets for younger and healthier adults.

Maintaining muscle mass in older age is important, and that requires protein. Photo by Barbara Olsen on Pexels

Here’s a crucial detail: the lower likelihood of reaching 100 among non-meat eaters was only observed in underweight participants. No such association was found in older adults of healthy weight.

Being underweight in older age is already strongly linked with increased risks of frailty and death. Body weight therefore appears to be a key factor in explaining these findings.

It’s also worth remembering that this was an observational study, meaning it shows associations rather than cause and effect. Just because two things occur together doesn’t mean one causes the other.

The findings also align with the so-called “obesity paradox” in ageing, where a slightly higher body weight is often linked to better survival in later life.

Notably, the reduced likelihood of reaching 100 observed among non-meat eaters was not evident in those who included fish, dairy or eggs in their diets. These foods provide nutrients that are essential for maintaining muscle and bone health, including high-quality protein, vitamin B12, calcium and vitamin D.

Older adults following these diets were just as likely to live to 100 as meat eaters. The researchers suggested that including modest amounts of animal-source foods may help prevent undernutrition and loss of lean muscle mass in very old age, compared with strictly plant-based diets.

What this means for healthy ageing

Rather than focusing on whether one diet is universally better than another, the key message is that nutrition should be tailored to your stage of life. Energy needs decline with age (due to decreased resting energy expenditure), but some nutrient requirements increase.

Older adults still require adequate protein, vitamin B12, calcium and vitamin D – especially to preserve muscle mass and prevent frailty. In older adulthood, preventing malnutrition and weight loss often becomes more important than long-term chronic disease prevention.

Plant-based diets can still be healthy choices, but they may require careful planning and, in some cases, supplementation to ensure nutritional adequacy, particularly in later life.

The bottom line is that our nutritional needs at 90 may look very different from those at 50, and dietary advice should reflect these changes across the lifespan. What works for you now might need adjusting as you age – and that’s perfectly normal.

Chloe Casey, Lecturer in Nutrition and Behaviour, Bournemouth University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Categories : Neurodegenerative DiseasesTags :

Researchers Affirm Long-held Belief that Viruses Can Trigger Parkinson’s Disease

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A new study shows that a common virus can induce Parkinson’s-like brain damage and movement problems

Source: CC0

Scientists usually use animal models when studying Parkinson’s disease because these models mimic the disease well. They are limited, however, because they require either gene modifications or the injection of toxicants, which may not accurately represent how the disease occurs in humans.

But now, researchers at Texas A&M University have developed a model that uses a nontoxic way to generate the symptoms of Parkinson’s: infection with a virus called Theiler’s murine encephalomyelitis virus (TMEV), a natural pathogen in mice.

Their study is a game changer because it proves that a simple viral infection can trigger the exact brain damage and physical disabilities in animal models that are seen in people with Parkinson’s disease – and it sets the stage for additional studies.

“The toxic-exposure models are useful for studying Parkinson’s, but not all people who are exposed to chemicals go on to develop Parkinson’s, so these models cannot show all the ways a disease as complex as Parkinson’s actually begins or develops over time in people,” said Candice Brinkmeyer-Langford, a neurogenerative disease expert with the Texas A&M University School of Public Health at Texas A&M Health.

Parkinson’s affects more than 10 million people worldwide, making it second only to dementia among brain disorders. It destroys the cells that produce dopamine, a chemical essential for smooth body movement, leading to problems with balance and walking, tremors in the hands or fingers and overall stiffness, as well as mental or emotional distress.

Its origins are unknown, but for decades, experts have believed that the disease could be triggered by the brain inflammation caused by viruses – even those contracted decades earlier – as well as by a combination of a person’s genetics and environmental factors. This idea recently was affirmed by Brinkmeyer-Langford and others at Texas A&M in the case of another devastating motor neuron disease, amyotrophic lateral sclerosis (ALS).

“Viruses are known to cause entirely different diseases based on a person’s genetics,” she said. “For example, the Epstein-Barr virus causes mononucleosis, but may also contribute to cancer or multiple sclerosis, and SARS-CoV-2 can attack the heart and brain as well as the lungs.”

For this pilot study to test the validity of TMEV in studying Parkinson’s, the researchers conducted experiments to measure the following:

  • Brain cell infection and damage. One week after infection, the researchers confirmed that the virus had infected the dopamine-producing brain cells. At one month after infection, the dopamine-producing cells were destroyed in the site of viral infection. Dopamine-induced behaviours were compared between 13 infected animal models and 14 healthy control animal models after administering a dopamine-mimicking drug which produced a distinct movement pattern confirming dopamine neuron loss. This test confirmed that the virus caused a significant loss of these crucial dopamine brain cells over time.
  • Speed and coordination. They compared 13 infected animal models against 14 healthy control animal models to track and measure their motor skills with a standard assessment called the pole test to determine if losing dopamine-producing cells causes the physical movement problems typically seen in Parkinson’s patients. Animal models infected with TMEV had slower times to complete the test compared to the healthy control models, and this still was the case at week 20, when the study ended.
  • Gait abnormalities. They used a specialised treadmill, which evaluated over 100 factors involved in walking, motor function and balance, to analyse how quickly and efficiently the animal models walked. The test confirmed that the virus caused physical weakness following the loss of dopamine producing cells due to viral infection, proving that the virus damaged the brain in a similar way as seen in Parkinson’s patients.

Now that this innovative model has been proven, Brinkmeyer-Langford said future studies will include testing the TMEV model directly against standard, older animal models used in Parkinson’s research, looking for early warning signs and biological markers for Parkinson’s and analyzing how the body’s immune response to a virus changes the brain.

“The clock is ticking, since the rapidly aging global population means the number of people with Parkinson’s is expected to jump significantly,” she said.

By Ann Kellett

Source: Texas A&M University

Categories : NeurologyTags :

A Sleepless Night Increases Synaptic Connections

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An increase in a marker for connections was associated with deeper sleep during later naps

Photo by Andrea Piacquadio

A night without sleep produced increased markers of connections between brain cells, showing that sleep in humans may be important for restoring cellular balance in the brain, according to a study published June 23rd in the open access journal PLOS Biology by David Elmenhorst from the Forschungszentrum Jülich Institute of Neuroscience and Medicine in North Rhine-Westphalia, Germany, and colleagues.

Scientists have long wondered why exactly humans and other animals need to sleep. One potential mechanism is that sleep is required to restore synaptic connections and homeostasis in the brain. Synapses – the connections between brain cells – become stronger during wakefulness. This increases the amount of energy the brain needs and leads to buildup of proteins in the brain. Sleep is thought to reset these levels, reducing synaptic connections and restoring homeostasis, but evidence has thus far been limited to animal models. To determine whether the synaptic homeostasis hypothesis is supported in humans, the authors of this study used positron emission tomography (PET) to look for markers of synaptic vesicle glycoprotein 2A (SV2A), a marker of brain synapses in 40 participants, half of whom had gone one night without sleep.

The authors found that after 28 hours of continuous wakefulness, the sleep deprivation group had higher measures of SV2A in several brain regions, including the hippocampus (an area important for memory), and the thalamus, an important information relay in the brain. When the sleep-deprived participants were allowed a two-hour nap, higher levels of SV2A were associated with more slow wave activity during sleep, a marker of deep sleep and sleep pressure. While SV2A is only a proxy for brain cell connections and the elevations were relatively small, the results support the synaptic homeostasis model of sleep, and suggest a biological connection between the need for sleep and the buildup of cell connections. 

The authors add, “During sleep deprivation, the brain remains awake longer and continues to process stimuli and information. Our study shows that after approximately 28.5 hours of wakefulness, a marker for synaptic density increases in several brain regions. This suggests that sleep deprivation not only causes fatigue but is also accompanied by measurable changes in neural connections.”

Provided by PLOS

Categories : Respiratory DiseasesTags :

Higher Vitamin A Levels Linked to Better Lung Function in Asthmatic Kids and Adults

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Vitamin D shows similar benefits in adults with asthma, including slower biological ageing

Photo by cottonbro studio from Pexels

Higher levels of circulating vitamin A are linked to better lung function in children and adults with asthma, while vitamin D shows similar benefits in adults, including slower biological ageing, finds the first study of its kind, published online in the respiratory journal Thorax.

Poor lung function is a key predictor of death, irrespective of whether or not a person has lung disease. And making sure that the lungs keep working well is essential for staving off long term respiratory conditions, explain the researchers.

Previously published research suggests that vitamins A and D both protect against and worsen asthma, as well as influencing lung development, depending on the dose and context, they add.

To clarify the role of these vitamins, the researchers drew on two groups of participants with asthma: 1165 children in the GACRS (Genetic Epidemiology of Asthma in Costa Rica Study); and 1041 adults in the ODOLLFA (Omic Determinants of Longitudinal Lung Function in Asthma).

Small molecules that fine-tune the activity of genes (serum microRNAs or miRNAs for short) and those that mark genes as either active or inactive (DNA methylation), plus levels of vitamins A and D, were measured in all the participants.

Lung capacity/health was assessed through measures of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and the FEV:FVC ratio.

In adults, further analysis assessed whether methylation status and miRNAs influenced the association between the vitamins and lung function or epigenetic ageing – the response of genes to external biological and environmental factors which then promotes cellular ageing.

The findings showed that children and adults with asthma and higher vitamin A levels had better lung function (FEV1 and FVC) than those with lower levels.

And among adults with asthma, those with higher vitamin D levels of at least 30 ng/ml had better lung function than those with lower levels. They also had less evidence of epigenetic ageing, suggesting that vitamin D may help slow biological ageing, particularly in people with asthma, say the researchers.

“These findings emphasise the value of adequate vitamin D, not only for lung health but also in slowing age-related processes,” they write.

In people with asthma, vitamin D deficiency is more common and is associated with more severe disease, worse asthma control, higher inhaled steroid need and more frequent  sudden worsening of asthma symptoms, they explain.

The researchers identified MiRNAs that regulate 248 genes commonly associated with vitamins A and D in both age groups, which, further analysis suggests, are involved in controlling inflammation and lung function.

This secondary analysis also revealed that changes in the expression of specific miRNAs strongly influence the effects of vitamins A and vitamin D on lung function and epigenetic ageing.

“To our knowledge, this is the first study to integrate vitamin A and D levels with lung function and epigenetic markers – miRNA expression and DNA methylation – in both children and adults with asthma,” write the researchers.

Lung function was inversely correlated with all age acceleration measures, reinforcing the link between respiratory health and ageing,” they add.

They conclude: “Our findings emphasise that epigenetic mechanisms play a key role in mediating the effects of vitamins on lung function in individuals with asthma, pointing to potential targets for personalised nutrition and therapeutic strategies in asthma care.”

In a linked editorial, Drs Sze Man Tse and Genevieve Mailhot of the CHU Sainte-Justine Research Center, Montreal, and the University of Montreal, caution: “While these findings open a novel line of investigation linking vitamin D, biological ageing and lung health, there is a need for further studies to clarify causality.”

But they add: “By examining the underlying biological mechanisms, [the researchers have] revealed a nuanced interplay between vitamins A and D, lung function, and their epigenetic mediators.

“Their findings highlight age-dependent and age-independent mechanisms, underscoring complex interactions between vitamin levels and lung physiology.”

And they conclude: “Overall, advancing our understanding of how nutritional exposures impact gene regulation may open new avenues for managing asthma across the lifespan.”

Source: The BMJ Group

Categories : EndocrinologyTags :

Cortisol from Adrenal Tumours Progressively Raises Cardiovascular Risk

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Landmark international study finds persistent mild cortisol excess drives hypertension progression, challenging the standard diagnostic test.

A graphic of a human skeleton, also showing the kidneys with the adrenal glands on top, highlighted in red.
The adrenal glands produce the steroid hormone cortisol, a master regulator of metabolism, blood pressure and immune function.

A major new study, led by the University of Birmingham and published in The Lancet Diabetes & Endocrinology, has shown that cortisol levels in patients with adrenal tumours are far less stable than previously assumed.

The study also identified that those in whom cortisol remains persistently elevated carry a significantly greater risk of worsening high blood pressure and a heavier overall cardiometabolic burden.

Cortisol, often referred to as the “stress hormone”, is a steroid hormone produced by the adrenal glands that acts as a master regulator of metabolism, blood pressure, and immune function. When benign tumours form on the adrenal glands (found incidentally in 3-7% of adults) they can cause the body to produce cortisol independently of normal regulatory controls, a condition known as mild autonomous cortisol secretion (MACS). Until now, it was unclear how cortisol levels in these patients change over time, and what that means for their long-term health.

The study of over 2500 patients is the largest study of its kind to examine how cortisol patterns evolve over time in patients with benign adrenal tumours and what this means for cardiovascular outcomes.

These findings should prompt us to think more carefully about which patients need closer follow-up, and whether active treatment to reduce cortisol excess – including surgery in selected cases – could protect their long-term cardiovascular health.

Alessandro Prete, Clinical Associate Professor in Endocrinology and Diabetes

The study followed 2525 patients with benign adrenal tumours for an average of nearly 7 years. Each patient underwent repeated hormonal testing using the 1mg overnight dexamethasone suppression test, the standard clinical test used to assess whether the adrenal gland is overproducing cortisol autonomously. Patients were classified based on whether their cortisol levels remained normal, remained elevated (persistent MACS), or changed between categories over time.

The researchers found that cortisol secretion status changed in 22% of patients, far more frequently than previously recognised, with most changes occurring within the first three years after diagnosis. These findings challenge the assumption that a single hormonal test is sufficient to characterise a patient’s long-term cortisol profile.

Patients with persistent MACS had the greatest overall cardiovascular burden and faced a 34% higher rate of worsening high blood pressure than those with persistently normal cortisol. Over 10 years, patients with persistent MACS lost an average of 2 years of well-controlled hypertension-free time compared with those whose cortisol remained normal – a clinically meaningful difference in long-term blood pressure control.

Cardiometabolic burden refers to the combined impact of interrelated metabolic and cardiovascular risk factors (including obesity, high blood pressure, type 2 diabetes, and high cholesterol) on overall health, predisposing serious, chronic diseases such as heart failure, heart attack, and stroke.

The study identified patients with persistently abnormal cortisol levels (persistent MACS) as a clinically important, higher-risk group who may benefit from closer monitoring and more proactive management of modifiable risk factors – including blood pressure, cholesterol, weight, and smoking. The results are also consistent with recent randomised trial data, also published in The Lancet Diabetes & Endocrinology, showing that surgery to remove the adrenal tumour can improve blood pressure control in MACS.

Professor Alessandro Prete, Clinical Associate Professor of Endocrinology in the Department of Metabolism and Systems Science at the University of Birmingham, Co-lead for the National Institute for Health and Care Research (NIHR) Biomedical Research Centre: Birmingham’s Women’s Metabolic Health theme, through which the study was delivered, and corresponding author and senior investigator of the study, said: “For many years, the assumption has been that a single hormone test at adrenal tumour diagnosis tells us everything we need to know about a patient’s cortisol status.

“This study shows that it is simply not the case – cortisol levels change over time in a substantial proportion of patients, and those in whom they remain persistently elevated are at a meaningfully higher risk of developing uncontrolled blood pressure.”

The study also provides important new evidence to inform the ongoing debate around whether, and how often, cortisol testing should be repeated in patients with benign adrenal tumours. Current guidelines recommend repeating the test only in specific clinical circumstances; the authors of the study are calling for prospective studies to determine whether repeated hormonal assessment contributes meaningfully to risk stratification beyond established cardiovascular risk factors. 

Source: University of Birmingham

Categories : CancerTags :

Uncovering Sex-specific Immune Differences in Glioblastoma

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Photo by Anna Shvets

Men and women experience many diseases very differently. Certain diseases present more commonly in one sex than in another. Some conditions like heart attacks may cause different symptoms in men and women. Some treatments work better or not at all for one sex over the other.

Cancer is no exception. There are major differences in male and female immune systems, a system critical for cancer’s growth and for successfully becoming cancer-free. For example, some immunotherapies work better in men than in women and vice versa.

Glioblastoma, the most common and fatal form of brain cancer, is more common and more deadly in men than in women. The reasons behind this difference and how the cancer’s biology differs between men and women remain largely unclear.

Now, a study has identified a cellular mechanism that differs between male and female laboratory models with glioblastoma. The study was published in the journal Nature Cancer and led by Defne Bayik, PhD, assistant professor of molecular and cellular pharmacology at the University of Miami Miller School of Medicine, and Asmita Pathak, PhD, a former postdoctoral fellow in the Bayik Lab.

“We have a growing appreciation that cancer doesn’t act the same way in men and women. There are differences in incidence rates. There are differences in treatment responses. There are differences in outcomes,” Dr Bayik said. “But we don’t really have a good, fundamental understanding of the mechanisms underlying these observational studies.”

Delving Into Immune Differences

To uncover that mechanism for glioblastoma, Dr Bayik and her colleagues focused on a certain class of immune cells in the brain known as myeloid-derived suppressor cells, or MDSCs. As their name suggests, these cells suppress other cells’ immune activity, especially that of T cells. In healthy contexts, their activity is important for regulating the immune system and keeping inflammation under control. But in the context of cancer, these cells are often recruited by tumours to suppress surrounding T cells and other immune cells, protecting cancerous cells from the rest of the immune system and allowing them to grow unchecked.

In previous work, Dr Bayik found sex-specific differences in the immune landscape of glioblastoma, with higher levels of monocytic myeloid-derived suppressor cells associated with disease in male laboratory models. Granulocytic MDSCs play a more prominent role in females. In studies of human glioblastoma tumours, she observed a similar pattern. Men tend to have more monocytic MDSCs within their tumours, Granulocytic MDSCs, or proteins associated with these cells, correlate with worse outcomes for women but not for men.

Women still constitute 40% of glioblastoma patients. By identifying these differences, we can better tailor treatments for both men and women.

Dr Defne Bayik

In the new study, Dr Bayik and her colleagues wanted to understand what drives this difference. How do granulocytic MDSCs act to promote cancer growth in female but not male laboratory models? In Dr Bayik’s previous study, she’d found several drug candidates that are predicted to act on granulocytic MDSCs. A few of these candidate drugs target proteins related to GABA, a brain signaling molecule also known as a neurotransmitter.

By exposing different populations of MDSCs to GABA in the lab, the scientists found that the neurotransmitter specifically affects cellular metabolism only in female granulocytic MDSCs. The process is unaffected in male MDSCs. They also found that this reprogramming of the cells’ metabolism by GABA made the granulocytic MDSCs more immunosuppressive. Finally, they found that blocking the GABA receptor in female laboratory models with glioblastoma improved their outcome. This had no effect on male laboratory models with the cancer.

Potential for treatment personalised by sex

Dr Bayik and her colleagues found that many of their lab findings held up in human samples donated by patients with glioblastoma. Tumour biopsies from women had higher levels of GABA and the GABA receptor in granulocytic MDSCs than did those from men. They also found that GABA reprograms granulocytic MDSC metabolism in women as it does in lab models.

These findings point to the potential for a sex-specific treatment for glioblastoma, Dr. Bayik said. She’s currently working to understand the basis for the difference in cellular metabolism in these immune cells between male and female laboratory models. Further uncovering the mechanism of this sex difference will help her and other scientists find new potential drug targets for the disease. MDSCs are involved in many other types of cance. Drugs that target these cells could have broader applications than just glioblastoma.

“Glioblastoma may be more common in men, but women still constitute 40% of patients,” said Dr Bayik. “By identifying these differences, we can better tailor treatments for both men and women.”

By Rachel Tompa, PhD

Source: University of Miami

Categories : Immunology Mental HealthTags :

Autoantibodies and Blood–Brain Barrier Dysfunction in Schizophrenia

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Source: CC0

A growing body of research has shown that autoimmunity influences certain psychiatric disorders. A new study by Nemani et al., currently in preprint, has shown that schizophrenia is strongly associated with an elevated level of autoantibodies that target the central nervous system. Using Rapid Extracellular Antigen Profiling (REAP) to screen 352 patients against 971 controls, the researchers found that schizophrenia is marked by an increased autoantibody burden that tracks with disease severity and duration, nearly doubling in the most chronic cases.

These immune responses are present near the start of the illness and tend to increase as the disease progresses, particularly targeting neuronal ion channels and synaptic proteins. Notably, certain autoantibodies appear to compromise the blood–brain barrier, which may further expose the brain to peripheral immune attacks.

The study also discovered that patients with a higher autoantibody burden respond less effectively to standard antipsychotic treatments like risperidone. However, clinical trials showed that these antibody levels significantly declined during successful treatment courses. These findings suggest that humoral autoimmunity is a core component of the disorder, potentially offering new pathways for immune-based therapies.

The article is available on the BioRxiv preprint server.

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Categories : AntibioticsTags :

Global Trial Shows Safer Antibiotic Option for Staph Blood Infection

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Methicillin resistant Staphylococcus aureus (MRSA) – Credit: CDC

A landmark international clinical trial, led in the UK by University College London researchers, has identified the optimal antibiotics for staph blood infection, a breakthrough that is set to reshape treatment for the life-threatening condition.

The SNAP trial found that a little used antibiotic, cefazolin, is as effective as and safer than the current UK standard therapy, flucloxacillin, for treating life-threatening staph blood infections.  More than half of staph blood infections lead to sepsis and 15% to 25% of those who get these infections die within three months.

The researchers also found that a commonly used antibiotic, penicillin, can be used when the staph is treatable with this in the laboratory. And that similarly this is probably as effective as flucloxacillin, and safer.

The findings from the SNAP trial, published in the New England Journal of Medicine (NEJM) and The Lancet, challenge the long-held assumption that flucloxacillin should remain the default treatment and provide important new evidence to guide treatment strategy.

Staph (Staphylococcus aureus) is a leading cause of deadly blood infection, associated with over 1 million deaths worldwide each year. While effective antibiotic treatments exist, there has been no clear agreement about which antibiotic leads to the best outcomes for patients.

The NEJM results – Comparing cefazolin and flucloxacillin

In the trial published in the NEJM, researchers compared antibiotics used to treat meticillin-susceptible Staphylococcus aureus (MSSA) infections (i.e. blood infections that are not resistant to the meticillin antibiotic). It found cefazolin is at least as good as flucloxacillin for helping people to survive this infection, and associated with fewer side effects and a lower risk of kidney injury. It compared cefazolin and flucloxacillin in 1341 adults with staph blood infections across eight countries taking part in this part of the trial.

In patients who received cefazolin there were fewer cases of changes in how the kidneys are working (as measured by blood tests). Such kidney changes can cause long-term health problems and occurred in fewer of those given cefazolin compared to those given flucloxacillin.

The Lancet results – Comparing benzylpenicillin and flucloxacillin

In the paper published in The Lancet, the trial evaluated whether penicillin could be used to treat penicillin-susceptible Staphylococcus aureus (PSSA) infections where laboratory testing confirmed the susceptibility to penicillin.

This trial compared penicillin and flucloxacillin in 281 adults with staph blood infections. Penicillin was found to be likely to be at least as good for helping people to live with this infection as flucloxacillin.

In patients who received penicillin there were similarly fewer cases of changes in how the kidneys are working (as measured by blood tests). These occurred in 11% of those given penicillin compared to 22% of those given flucloxacillin. Mortality was also 14% in the penicillin group compared with 22% in the flucloxacillin group.

Professor Anna Goodman, UK lead of the SNAP trial at the UCL Innovative Clinical Trials, said: “This trial fills a major research gap. Our results strongly support cefazolin as the new first treatment for most adults with these infections. They also show a role for penicillin in some cases. It’s been helpful to deliver it in collaboration with researchers around the world and patients who have been affected by the condition, who we found via the UK Sepsis Trust.

“The results represent huge progress in the management of this disease with the first change in our approach to antibiotics in decades. Not only are cefazolin and penicillin as effective as flucloxacillin at treating penicillin- and meticillin-susceptible staph blood infection, but they also lead to significantly fewer abnormal blood tests.”

Staph infections are caused by bacteria called Staphylococcus aureus. They most often affect the skin and cause relatively minor problems. However, if the bacteria enter the bloodstream or other parts of the body, they can cause serious infections such as blood poisoning, blood infection or sepsis.

These more serious infections can affect anyone, but individuals at higher risk include people with catheters in their veins (as happens when people receive renal replacement therapy also called haemodialysis) or implanted devices (such as pacemakers), and people with diabetes. Those living with cancer and on immune suppressing medication, those who cannot get out of bed, and those who inject drugs are also more vulnerable to these infections.

The Royal Melbourne Hospital’s Professor Steven Tong, an infectious diseases physician at the Doherty Institute in Australia and global co-lead investigator of the SNAP Trial, said the results provide clear evidence that cefazolin should be considered the first-line option to treat MSSA blood infections.

“In the treatment of MSSA blood infections, there is an 89% probability that cefazolin is associated with lower mortality,” said Professor Tong.

“Patients treated with cefazolin fare better, with fewer deaths within 90 days (15% compared to 17% for those who received flucloxacillin). Cefazolin was also associated with fewer cases of acute kidney injury, at 14%, compared to 20% with flucloxacillin.

“The results are sufficiently compelling that I immediately made the switch in my own clinical practice.”

A shift away from flucloxacillin

Researchers said these results mark a turning point in the treatment of MSSA and PSSA blood infections, signalling a shift in clinical practice.

Penicillin was once widely used to treat Staphylococcus aureus, but antibiotic resistance of staph led clinicians to adopt flucloxacillin as the standard treatment for MSSA and PSSA blood infections. The findings support moving away from flucloxacillin as the default treatment for MSSA and PSSA blood infections, given safer alternatives are available.

The new results mark the first major finding from the ongoing SNAP trial, which aims to improve treatment for Staphylococcus aureus infections around the world. These parts of the trial took place in Australia, Canada, Israel, the Netherlands, New Zealand, Singapore, South Africa and the UK – each supported by regional funders working together to form one global network.

Global leadership was provided by the University of Melbourne trial team led by Professor Steven Tong and Professor Josh Davis.

So far, over 6000 participants have been enrolled in over 150 sites in those countries stated, and more recently in Germany and Sweden, Germany, Japan, Malaysia, and the United States.  The trial will continue testing new approaches to improve outcomes for patients facing this serious infection.

Translating the findings

Researchers say the next challenge will be translating the findings into routine clinical practice.

While cefazolin availability may need to increase in some countries, researchers say implementation will ultimately depend on hospitals, laboratories and guideline groups incorporating the findings into clinical care. 

Professor Goodman said: “Sepsis and staph blood infections are devastating for those affected and those who care for them. We are grateful to all those who took part and supported these two trials which will change practice.  The platform trial continues as we ask further important questions in this area.”

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Source: University College London

Categories : General Interest Surgeries & ProceduresTags :

How Wits Donald Gordon Medical Centre is Advancing Specialised Reconstructive Surgery in South Africa

On By ModernMedia
Photo by Natanael Melchor on Unsplash

When 12-year-old Eugene underwent a highly specialised facial reanimation procedure earlier this year, the surgery represented something profoundly human, the possibility of smiling for the first time.

Born with Moebius syndrome, a rare neurological condition that affects facial movement and expression, Eugene had spent his life unable to smile, blink properly or express emotion through facial movement. And while his story is emotionally powerful, it also shines a light on a far broader healthcare reality, the growing importance of highly specialised reconstructive surgery in restoring not only appearance but movement, function, dignity and quality of life.

At Wits Donald Gordon Medical Centre (WDGMC), reconstructive microsurgery is helping redefine what is possible for patients facing some of the most complex medical challenges, from congenital conditions and cancer to severe trauma and tissue loss.

Often misunderstood as a field focused primarily on cosmetic procedures, reconstructive microsurgery sits at the intersection of surgical precision, innovation and long-term patient rehabilitation. These procedures frequently involve transplanting tissue, muscle and nerves from one part of the body to another and reconnecting blood vessels, often measuring less than two millimetres in diameter, under microscopic magnification.

Leading this work at WDGMC is Dr Dimitri Liakos, a plastic and reconstructive surgeon with fellowship training in reconstructive microsurgery and super microsurgery.

Dr Dimitri Liakos, a plastic and reconstructive surgeon with fellowship training in reconstructive microsurgery and super microsurgery.

“These procedures are not simply about appearance,” says Dr Liakos. “They are about restoring function, movement and ultimately helping patients regain parts of their lives that were lost or that they were born without.” In Eugene’s case, surgeons transferred functioning muscle together with its blood and nerve supply into the face, reconnecting these delicate structures under a microscope so movement could gradually return over time.

Eugene’s procedure was facilitated through the support of the Smile Foundation, which works to improve access to reconstructive surgery for children requiring specialised care.

“We are deeply grateful to Wits Donald Gordon Medical Centre and Dr Dimitri Liakos for their dedication in supporting Eugene on his journey,” says Tarri Parfitt, CEO of Smile Foundation. “It is truly remarkable to open a world-class facility to this family and provide care at the highest level of expertise. Facial reanimation surgery is profoundly life-changing. For Eugene, it represents the possibility of expression, connection and a future he may never have imagined before. For Smile, it was also an invaluable opportunity for other surgeons to learn from such a rare and complex case, turning one surgery into the potential to help many more children like Eugene. We highly value the opportunity to work alongside Wits Donald Gordon Medical Centre on cases such as this and look forward to helping many more children together.”

While these procedures are performed in highly specialised centres globally, access to this level of care remains limited in South Africa due to the advanced infrastructure, multidisciplinary expertise and years of specialised training required to perform them successfully.

For WDGMC, however, the ability to perform these surgeries forms part of a broader commitment to advancing highly specialised care within South Africa’s healthcare system while simultaneously strengthening academic medicine and specialist training.

As an academic hospital affiliated with the University of the Witwatersrand, WDGMC has become an important training environment for complex reconstructive microsurgery in South Africa. The hospital recently established the country’s first reconstructive microsurgery fellowship programme for qualified plastic surgeons, helping expand the number of specialists capable of performing these highly technical procedures.

“We have a responsibility not only to perform these surgeries, but to transfer the skill,” says Dr Liakos. “If we do not train future microsurgeons, access to this level of specialised care will remain limited.”

According to Dr Liakos, successful reconstructive microsurgery depends not only on surgical expertise but on building the right multidisciplinary environment around patients.

“To do these cases successfully, you need a dedicated team and an environment that functions seamlessly,” he explains. “Microsurgery is never a one-person effort. It is the nursing staff, anaesthetists, theatre teams and systems around you that make these outcomes possible.”

For surgeons working in the field, the impact of reconstructive microsurgery extends far beyond the operating theatre.

“These surgeries can take 10 or 12 hours. They are physically and emotionally demanding,” says Dr Liakos. “But when you step back and realise that what you are doing may change the course of a person’s life forever, it gives meaning to every moment spent in theatre.”

As WDGMC continues to build on its reconstructive microsurgery programme and the country’s first fellowship of its kind, the hospital is helping shape a future in which South African patients can access world-class reconstructive care close to home and in which the specialists capable of providing that care are trained locally.