Tag: 21/9/21

Categories : PaediatricsTags :

Better Outcomes in Children Receiving Living Donor Liver Transplants

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Phot by Ben Wicks on Unsplash

A new study from Children’s Hospital Los Angeles pooled examining outcomes for 8000 paediatric patients across four continents revealed that children receiving living donor liver tissue for transplants have a far lower risk of serious complications.

With medical advances and the liver’s fantastic regeneration capacity, healthy individuals can donate a portion of their liver. While many countries now exclusively perform living donor liver transplants, in the United States, only 8% of liver transplants are from living donors, such as those done by Children’s Hospital Los Angeles.

“We have published large-scale studies showing the benefits of living donor liver transplantation in adults,” said Juliet Emamaullee MD, PhD, Research Director, Division of Abdominal Organ Transplantation, Children’s Hospital Los Angeles. “And we’ve observed the benefits in kids too. But we really wanted to evaluate it systematically, to provide evidence from around the world to back up what we’ve seen.”
The screened over 2500 studies, distilling relevant studies, compiling data from 8000 paediatric patients who had received either living or deceased donor livers. Results showed that a year after the procedure, children who had received living donor liver transplants had nearly twice the survival rate while the risk of organ rejection was nearly halved.

Living donor tissue for liver transplants has a number of benefits, which may explain some of the difference in outcomes. Patients may need to wait a shorter time as they do not need to wait for an appropriately sized deceased organ donor, a particular challenge for infants and toddlers, who make up over 50% of paediatric liver transplants. But the biggest advantage may be that patients can be healthier at the time of their procedure.

“When a liver becomes available, the basic rule is that it goes to the sickest child,” said Dr Kohli. “And that makes sense. We don’t want any child dying on the waiting list.” Unfortunately though, this means that children can be on the waiting list for years before getting a transplant. They can be very ill as a result at the time of transplant, possibly affecting how well a child does once they receive a new liver.

“These results are important and relevant for families,” said Dr Emamaullee. “Not all children are at a center that offers living donor liver transplant. Now we have the data to suggest that kids really should be offered this option. Families should have the chance to donate to their children rather than having to wait until an organ donor comes along.”

“As a paediatrician, I want children getting the best chance possible,” said Dr Kohli. “Studies like these inform our care. They show us how to do the best possible job for our kids.”

Source: Children’s Hospital Los Angeles

Categories : PaediatricsTags :

Early Developmental Intervention Dramatically Cuts Autism Risk

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A first-of-its-kind study has shown that parent-led therapy supporting the social development of babies with early autism signs greatly reduced the odds of a later autism. 

The research, led by CliniKids at the Telethon Kids Institute and published in JAMA Pediatrics, found that a diagnosis of autism at age three was only a third as likely in children who received the pre-emptive therapy (iBASIS-VIPP)compared to those who received usual treatment.

The findings were the first evidence showing that a pre-emptive intervention during infancy could result in such a significant improvement in children’s social development that they then fell below the threshold for an autism diagnosis.

Study leader Professor Andrew Whitehouse, Telethon Kids Institute, said: “The use of iBASIS-VIPP resulted in three times fewer diagnoses of autism at age three. No trial of a pre-emptive infant intervention, applied prior to diagnosis, has to date shown such an effect to impact diagnostic outcomes – until now.”

Professor Whitehouse said many therapies for autism tried to replace developmental differences with more ‘typical’ behaviours. Instead, iBASIS-VIPP attempts to work with each child’s unique differences, creating a social environment around the child helping them learn in a way optimised for them.

“The therapy uses video-feedback to help parents understand and appreciate the unique abilities of their baby, and to use these strengths as a foundation for future development,” said Professor Whitehouse. “By doing so, this therapy was able to support their later social engagement and other autistic-related behaviors such as sensory behaviors and repetitiveness, to the point that they were less likely meet the ‘deficit-focused’ diagnostic criteria for autism.”

“We also found increased parental sensitivity to their baby’s unique communication and an increase in parent-reported language development. Other general aspects of development were not affected.” The children falling below the diagnostic threshold still had developmental difficulties, but by working with each child’s unique differences, rather than trying to counter them, the therapy has effectively supported their development through the early childhood years.”

The four-year randomised clinical trial enrolled babies aged 9-14 months, all of whom having shown early behavioural signs of autism. Over five months, half received the video intervention, while a control group received current best practice treatment.

Eighty-nine children completed an assessment at the start of the study, at the end of the therapy period, and when they were two and three years of age. With the high prevalence of autism worldwide, the implications of the findings were enormous, said Professor Whitehouse. Around 2% of all children in Australia have an autism diagnosis.
“Autism is not typically diagnosed until three years of age, however, interventions commencing during the first two years of life, when the first signs of development difference are observed and the brain is rapidly developing, may lead to even greater impact on developmental outcomes in later childhood,” Professor Whitehouse said.

Professor Whitehouse said that a follow-up of study participants in later childhood, when autism behaviours may be more apparent, would be critical to determining the longer-term significance of the video intervention.

Source: Telethon Kids Institute

Categories : Metabolic DisordersTags :

Hair Loss Tied to High-fat Diets or Genetic Obesity

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A mouse study by Japanese researchers found that high-fat diets or genetically induced obesity can cause loss of hair follicles.

Obesity is linked to the development of numerous diseases in humans, such as heart disease and diabetes. However, it’s not fully clear how body organs specifically deteriorate and lose functionality from chronic obesity. Using mice, researchers from Tokyo Medical and Dental University (TMDU) examined how a high-fat diet or genetically induced obesity can affect hair thinning and loss. The findings, published in Nature, indicated that obesity can lead to depletion of hair follicle stem cells (HFSCs) by inducing certain inflammatory signals, blocking hair follicle regeneration and ultimately resulting in loss of hair follicles.

HFSCs normally renew themselves every hair follicle cycle. With progressing age, HFSCs fail to renew themselves leading to fewer HFSCs and therefore hair thinning. Although overweight people have a higher risk of male pattern balding, whether obesity accelerates hair thinning, how it does this and the molecular mechanisms behind it have remained largely a mystery. The TMDU group aimed to address those questions and identified some of the mechanisms.

Explaining the study, study lead author Hironobu Morinaga said: “High-fat diet feeding accelerates hair thinning by depleting HFSCs that replenish mature cells that grow hair, especially in old mice. We compared the gene expression in HFSCs between HFD-fed mice and standard diet-fed mice and traced the fate of those HFSCs after their activation.

“We found that those HFSCs in HFD-fed obesed mice change their fate into the skin surface corneocytes or sebocytes that secrete sebum upon their activation. Those mice show faster hair loss and smaller hair follicles along with depletion of HFSCs.

“Even with HFD feeding in four consecutive days, HFSCs show increased oxidative stress and the signs of epidermal differentiation.”

“The gene expression in HFSCs from the high-fat–fed mice indicated the activation of inflammatory cytokine signaling within HFSCs,” said senior author Emi Nishimura. “The inflammatory signals in HFSCs strikingly repress the Sonic hedgehog signaling that plays a crucial role in hair follicle regeneration in HFSCs.

However, the researchers noted that activating the Sonic hedgehog signaling pathway in this process can rescue the depletion of HFSCs. “This could prevent the hair loss brought on by the high-fat diet,” said Nishimura.

This study shines a light on cellular and tissue dysfunction from a high-fat diet or genetically induced obesity, and could lead to prevention and treatment of hair thinning along with greater understanding of obesity-related diseases.

Source: Tokyo Medical and Dental University

Categories : Cardiovascular DiseaseTags :

A Year of Exercise Reverses Heart Failure Signs

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In a small study, a year of exercise training helped to maintain or increase the youthful elasticity of the heart muscle among people in late middle age showing early signs of heart failure.

Published in Circulation, the research reinforces the notion that “exercise is medicine,” an important shift in approach, according to the researchers.

The study focused on heart failure with preserved ejection fraction, which is characterised by stiffening of the heart muscle and high pressures inside the heart during exercise. Once established, the condition is largely untreatable and causes fatigue, excess fluid in the lungs and legs, and shortness of breath.

“It is considered by some to be one of the most important virtually untreatable diseases in cardiovascular medicine,” said senior author Dr Benjamin Levine,  professor of internal medicine at UT Southwestern and director of the Institute for Exercise and Environmental Medicine at Texas Health Presbyterian Dallas. “So, of course, if there are no therapies, then the most important thing to do is to figure out how to prevent it from happening in the first place.”

In previous studies, prolonged exercise training was shown to improve heart elasticity in younger people, but was ineffective for heart stiffness in people 65 and older. The researchers decided to see if committed exercise could improve heart stiffness in healthy, sedentary men and women ages 45 to 64.

The study recruited 31 participants who showed some thickening of the heart muscle and an increase in blood biomarkers associated with heart failure, even though they had no other symptoms such as shortness of breath.

Eleven were randomly assigned to a control group and prescribed a program of yoga, balance and strength training three times a week. The rest were assigned to an individually tailored exercise regimen that gradually ramped up until the participants were doing intensive aerobic interval training for at least 30 minutes at least twice a week, plus two to three moderate-intensity training sessions and one to two strength training sessions each week. 

After one year, the group assigned vigorous exercise training showed a physiologically and statistically significant improvement in measures of cardiac stiffness and cardiorespiratory fitness, compared to no change in the control group.

The results suggest late middle age may be a “sweet spot” for using exercise to prevent heart failure with preserved ejection fraction, before the heart gets too stiff, Prof Levine said. He compared the heart muscle to an elastic band: a new one stretches easily and snaps right back.

“That’s a youthful cardiovascular system,” he said. “Now, stick it in a drawer and come back 30 years later—it doesn’t stretch, and it doesn’t snap back. And that’s one of the things that happens to the circulation, both the heart and the blood vessels as we age, particularly with sedentary aging.”

However, the study cannot determine if the participants will still go on to develop heart failure. This question will have to be addressed by larger studies. Furthermore, it is difficult for people to adhere to an exercise program, and the intensive intervention studied may be difficult and expensive to replicate on a large scale.

Source: American Heart Association

Categories : COVIDTags :

Stockpiling Could Cause 241 Million Vaccine Doses to be Wasted

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Image by Mika Baumeister on Unsplash

Analytics company Airfinity estimates the G7 and EU will have an excess of 1 billion vaccine doses by the end of 2021, of which 10% are expected to expire. 

When factoring the time taken to distribute and administer the doses in Lower Income Countries (LICs) and Lower Middle Income Countries (LMICs), the proportion rises. Many of these countries will refuse vaccines that don’t have at least a two month shelf life. Taking into account this two month shelf, 241 million doses could be wasted by the end of 2021, amounting to a quarter of the G7 and EU surplus stock. 

The available vaccines in the G7 and EU, together with already purchased doses and COVAX deliveries, are sufficient for LICs and LMICs to vaccinate 70% of their populations by May 2022. Airfinity estimates that total global COVID cases are likely to exceed 400 million by mid-2022 and immediately redistributing vaccines could potentially avert nearly 1 million deaths from the virus in that time frame. 

“Currently doses tend to get shared in low volumes, at short notice, and with shorter than ideal expiry dates – making it a huge logistical lift to allocate and deliver these to countries able to absorb them,” says Aurélia Nguyen, managing director of the COVAX facility.

Vaccine manufacturers are now making 1.5bn doses every month.

“They’re producing a huge number of doses. It has scaled up immensely over the last three or four months,” Dr Matt Linley, lead researcher at Airfinity, told BBC News.

“I don’t think it was necessarily rich countries being greedy, it’s more that they didn’t know which vaccines would work,” says Dr Linley. “So they had to purchase several of them.”

Airfinity hopes to show governments that there are enough vaccines to fulfil their needs, and thanks to this secure supply they can donate without stockpiling.

“They don’t want to be caught off guard,” said Agathe Demarais. “It’s also about domestic political pressure because part of the electorate would probably be very unhappy to see vaccines being donated, if there is a feeling that they’re still needed at home.”

Co-founder and CEO of Airfinity, Rasmus Bech Hansen said: “The world has witnessed two extraordinary scientific achievements in the pandemic: The fast development of highly effective vaccines and the unprecedented scale up of production.For the world to get the full benefit of this, our data shows, we need a third equally unprecedented achievement: A large scale, rapid, globally coordinated, science driven vaccination campaign.” 

Source: Airfinity