Tag: 13/9/22

Categories : Metabolic DisordersTags : Leave a comment

30-year Diabetes Study Determines HbA1c Threshold for Complications

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Diabetes - person measures blood glucose
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The levels of long-term blood sugar, HbA1c, can be used to accurately determine the risk of a person with type 1 diabetes developing eye- and kidney complications. A Swedish study, published in Diabetes Care, followed individuals after the onset type 1 diabetes for 30 years and showed that this level should under 53mmol/mol (7%).

People with diabetes may experience damage to the small blood vessels in various organs. The reasons for this are unclear, but it has been known since the 1990s that good control of blood sugar levels reduces the risk of complications. It has, however, not been clear what level of long-term sugar, HbA1c, people with type 1 diabetes should have in order to avoid serious damage to blood vessels in the eyes and kidneys.

“Our study determines accurately the levels of long-term sugar that can avoid complications. This knowledge can increase a person’s motivation to keep their blood sugar level under control,” said study leader Hans Arnqvist, professor emeritus at Linköping University.

Researchers in the current study, known as VISS (Vascular Diabetic Complications in Southeast Sweden), have followed all children and adults under 35 who developed type 1 diabetes during the period 1983–1987 in Southeast Sweden. All 447 newly diagnosed persons in the region during this period were included in the study. The researchers have followed the patients’ HbA1c values, which reflect their average blood sugar levels during a longer period. They have also monitored the development of eye- and kidney damage in these patients for a period of between 32 and 36 years after diagnosis.

In type 1 diabetes, the small blood vessels in the eye are particularly susceptible to damage. Nearly all patients experience small haemorrhages in the eye that do not affect their vision. In some cases, proliferative retinopathy develops, forming new blood vessels which can lead to blindness. The macula of the retina can also be damaged, leading to blurred vision.

While the kidneys are not as sensitive to high blood sugar levels as the eye, the important small blood vessels here can also be damaged, leading to albuminuria. The damage to the kidneys eventually leads to impaired kidney function and, in serious cases, kidney failure.

In healthy individuals, the blood sugar level is very closely controlled, with a maximum HbA1c level of 42mmol/mol (6.0%).

“The results of our study show that people with type 1 diabetes for at least 32 years should keep their mean long-term sugar level below 53mmol/mol (7.0%), if they are to completely avoid serious damage. The risk of eye- and kidney complications increases as the level increases. Our conclusions relate to avoiding complications arising from blood vessel damage. But if a patient has problems with low blood sugar, hypoglycaemia, it’s not possible to control the blood sugar level so strictly,” said Prof Arnqvist.

The target level for HbA1c that is suggested by the results of the VISS study agrees with the individual targets recommended by the American Diabetes Association. In Sweden, target levels are given for groups, rather than individuals.

The previous follow-up by the research group was conducted 20 years after the onset of disease. Now after 30 years, the results show that damage has arisen at lower blood sugar levels than was the case after 20 years.

More patients have experienced damage, despite having blood sugar levels that are not higher than those they have previously had. In other words, it seems that the threshold for developing complications falls gradually with time. This means that the study does not allow any conclusions for the recommended blood sugar levels of people with type 1 diabetes longer than 30 years after diagnosis.

Source: Linköping University

Categories : Paediatrics Substance UseTags : Leave a comment

Prenatal Cannabis Exposure Impacts Persist to Pre-adolescence

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Children
Photo by Ben Wicks on Unsplash

Children who were exposed to cannabis in the womb continue to show elevated rates of symptoms of psychopathology (depression, anxiety and other psychiatric conditions), even as they reach pre-adolescence (aged 11–12), according to research published in JAMA Pediatrics.

The study, led by Ryan Bogdan, associate professor at Washington University in St. Louis, is a follow-up to 2020 research from the Bogdan lab that revealed younger children who had been prenatally exposed to cannabis were slightly more likely to have had, inter alia, sleep problems, lower birth weight and lower cognitive performance.

In both cases, the effect is strongest when looking at exposure to cannabis after the pregnancy is known. To find out whether or not these associations persisted as the children aged, David Baranger, a postdoctoral researcher in the BRAIN Lab, revisited the more than 10 500 children from the 2020 analysis, who were an averaged of 10 years old in 2020.

The data on the children and their mothers came from the Adolescent Brain and Cognitive Development Study (ABCD Study), an ongoing study of nearly 12 000 children, beginning in 2016 when they were 9–10 years old, and their parents or caregivers.

This seemingly small change in age – from 10 to 12 – is an important one. “During the first wave, they were just children. Now they’re edging up on adolescence,” Baranger said. “We know this is a period when a large proportion of mental health diagnoses occur.”

An analysis of the more recent data showed no significant changes in the rate of psychiatric conditions as the children aged; they remain at greater risk for clinical psychiatric disorders and problematic substance use as they enter the later adolescent years.

“Once they hit 14 or 15, we’re expecting to see further increases in mental health disorders or other psychiatric conditions – increases that will continue into the kids’ early 20s,” Baranger said.

Source: University of Washington in St. Louis

Categories : Mental HealthTags : Leave a comment

Explaining the Power of ‘Super-recognisers’

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Old man with magnifying glass
Image by Mar Lezhava on Unsplash

Some people have the ability to never forget a face, and some help police departments and security agencies identify suspects. It is only now that researchers have come to understand a bit more about this ability, which until now was believed to derive from photographic memory.

In a paper published in Psychological Science, psychologists challenged this view, proving that super-recognisers look at faces just like all of us, but do it faster and more accurately. 

UNSW Sydney researcher and study lead author, Dr James Dunn, explained that when super-recognisers catch a glimpse of a new face, they divide it into parts and then store these in the brain as composite images.

“They are still able to recognise faces better than others even when they can only see smaller regions at a time. This suggests that they can piece together an overall impression from smaller chunks, rather than from a holistic impression taken in a single glance,” Dr Dunn said. 

Co-lead author Dr Sebastien Miellet, University of Wollongong (UOW) expert in active vision, used eye-tracking technology to analyse how super-recognisers scan and process faces and their parts. 

“With much precision, we can see not only where people look but also which bits of visual information they use,” Dr Miellet said.

When studying super-recognisers’ visual processing patterns, Dr Dunn and Dr Miellet realised that contrary to typical recognisers, super-recognisers focused less on the eye region, instead distributing their gaze more evenly than typical viewers, extracting information from other facial features, particularly when learning faces. 

“So the advantage of super-recognisers is their ability to pick up highly distinctive visual information and put all the pieces of a face together like a puzzle, quickly and accurately,” Dr Miellet said. 

The researchers will continue to study the super-recogniser population. Dr Miellet says that one hypothesis is that super-recognisers’ superpower may stem from a particular curiosity and behavioural interest in others. Super-recognisers may also be more empathetic. 

“In the next stages of our study, we’ll equip some super-recognisers and typical viewers with a portable eye tracker and release them onto the streets to observe, not in the lab but in real life, how they interact with the world,” Dr Miellet said. 

Source: University of Wollongong Australia

Categories : General Interest Injury & TraumaTags : Leave a comment

Oldest Known Successful Amputation Dates Back 31 000 Years

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Mariano, Public domain, via Wikimedia Commons

At a site in Borneo, archaeologists have unearthed the oldest case of surgical amputation to date, a remarkable feat of prehistoric medical practice.

Published in Nature, the researchers describe the skeletal remains of a young adult found in a cave in Borneo, who had part of the left lower leg and left foot amputated, probably as a child, at least 31 000 years ago. The person lived for at least another six to nine years after the procedure, surviving into adulthood where they died from an unknown cause, possibly in their 20s.

The prehistoric surgery is a remarkable feat; preventing infections is difficult even in modern surgical amputations.

Study co-lead author, Dr Melandri Vlok, at University of Sydney said the find is “incredibly exciting and unexpected.”

“The discovery implies that at least some modern human foraging groups in tropical Asia had developed sophisticated medical knowledge and skills long before the Neolithic farming transition,” said bioarchaeologist Dr Vlok, an expert in ancient skeletons.

The skeleton of the young adult was carefully buried within LiangTebo cave – located Borneo in East Kalimantan, in a limestone karst area home to some of the world’s earliest dated rock art.

The bones were uncovered by archaeologists just days before borders closed for the COVID pandemic in March 2020. Dr Vlok was invited to study the bones when they were brought back to Australia.

“No one told me they had not found the left foot in the grave,” Dr Vlok said. “They kept it hidden from me to see what I would find.”

As Dr Vlok laid the bones out, the left leg looked withered, and was the size of a child’s, but the individual was an adult. She unwrapped the part of the leg that contained the stump and noticed the cut was clean, well healed and had no evidence of any infection. “The chances the amputation was an accident was so infinitely small,” Dr Vlok said. “The only conclusion was this was stone age surgery.”

Dr Vlok ran to the office to tell her research colleagues what she had found. “I told them I thought it looked like a surgical amputation,” she said. “It wasn’t until then that they said they already knew the foot was missing.” Dr Vlok had just confirmed their suspicions. The foot was never placed in the grave to begin with.

An accident in difficult terrain

While the cause for the amputation was unclear, the individual also had a very well healed neck fracture and trauma to their collar bone that may have occurred during the same event, said Dr Vlok.

“An accident, such as a rock fall may have caused the injuries, and it was clearly recognised by the community that the foot had to be taken off for the child to survive,” she said.

The location of the cave is surrounded by extremely rugged terrain, and accessing the site was challenging, making the individual’s survival after the the surgery even more remarkable. The finding will provide even more insight into prehistoric medicine, the researchers said.

Source: University of Sydney

Categories : CancerTags : Leave a comment

‘Striking’ Colon Cancer Trial Data gets Standing Ovation

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In a clinical trial, nearly every one of the 112 patients with mismatch repair-deficient (dMMR) colon cancer achieved a pathologic response with just two cycles of neoadjuvant immunotherapy, prompting a presentation panellist to describe it as “striking data” – though a note of caution was given.

Patients in the NICHE-2 single-arm study received PD-1 plus CTLA-4 blockade – nivolumab plus ipilimumab, and successfully underwent surgical resection, 98% on time, meeting the study’s primary safety endpoint, reported Myriam Chalabi, MD, at the at the European Society for Medical Oncology (ESMO) annual congress.

And with a median follow-up of 13.1 months, the disease-free survival (DFS) rate was 100%, said Dr Chalabi of the Netherlands Cancer Institute in Amsterdam. She pointed out that, by this point, the expected rate for this patient population was about 15%. The primary efficacy endpoint for the trial is DFS at 3 years, with success defined as a rate of 93% (data are expected next year).

A standing ovation erupted when Dr Chalabi displayed the waterfall plot showing the depth of pathologic response with just four weeks of nivolumab plus ipilimumab.

Credit: NICHE-2 Study

Among the 107 patients evaluable for efficacy, all but one had a pathologic response, 95% had a major pathologic response (MPR), and 67% had a pathologic complete response (pCR), ie no residual viable tumour in both the primary tumour bed and lymph nodes.

“As you can appreciate, the pathologic regression observed was near-complete or complete in almost all patients,” she said.

In contrast, pathologic response rates in the range of 5% to 7% for this population have been shown in prior trials involving neoadjuvant chemotherapy, said Chalabi.

Some 10–15% of colon cancers are classified as dMMR, she explained, which are highly sensitive to immune checkpoint inhibitors, where a number of agents have been approved for the metastatic setting.

The first to comment in Q&A, Alexander Eggermont, MD, PhD, stressed the potential impact of the findings, saying that patients with dMMR tumours scheduled for resection “should be taken off the surgical program.”

“They should be sent to the medical oncologist for the first dose of ipi/nivo,” he said. “We will live the day that they will not undergo surgery anymore after these schedules – that’s the next step.”

A multicentre, single-arm study, NICHE-2 enrolled 112 patients with previously untreated non-metastatic dMMR colon cancer undergoing surgery. The first cycle of neoadjuvant treatment included ipilimumab (1mg/kg) and nivolumab (3mg/kg). The second cycle, given two weeks later, was limited to nivolumab alone. After the first dose, median time to surgery was 5.4 weeks.

The trial defined pathologic response as 50% or less residual viable tumour; MPR was defined as 10% or less residual viable tumour, and included patients with pCRs in the primary tumour but viable tumour in the lymph nodes.

The median age of patients was 60, and 58% were women. About three-fourths had high-risk stage III disease, 13% had low-risk stage III disease, and 13% had stage I/II disease. About half had radiologic high-risk disease (both T4 and N2), said Dr Chalabi, and abdominal wall involvement was common.

When asked whether randomised data would be needed to make this approach standard, Dr Chalabi pointed out the group with T4 tumours.

“I wouldn’t want to randomise those patients,” she said. “Surgeons usually would prefer to have some type of downstaging before continuing on to surgery in order to increase the chances of achieving tumour-free resection margins and also to limit the extent of surgery needed to achieve that.”

The case for randomisation is stronger in earlier disease, she said, but if recurrences can be prevented even in stages where recurrence is more rare, such as stage II tumours (about 10% at 3 years), “we’re curing 10% more patients.”

A little less than a third of patients had Lynch syndrome, and pCRs were more frequent in this subset (78% vs 58% in those with sporadic tumours). Immune-related adverse events (AEs) were reported in 61% of patients, with 4% being grade 3/4.

When the prospect of a NICHE-3 trial came up, Dr Chalabi said that it ideally would have been an international study to validate the approach. However, a subsequent trial is being developed and will likely involve nivolumab plus anti-LAG-3 relatlimab, “which is a shame,” she noted.

“If we do get similar responses with nivolumab and anti-LAG-3, then that may be an avenue to test organ-sparing approaches with that combination in this population,” she added.

Source: MedPage Today