Tag: 1/5/23

Prehabilitation Improves Orthopaedic Surgery Outcomes

Photo by Barbara Olsen on Pexels

Pre-surgery exercise and education, or ‘prehabilitation’, can significantly improve outcomes for patients undergoing orthopaedic surgery, according to new research published in JAMA Network Open.

An ageing population plus the COVID pandemic has put great strains on healthcare systems, creating a longer waiting time for patients due to undergo routine elective surgical procedures. This can cause mental and physical deconditioning in patients, potentially impacting their surgical outcomes.

The study found prehabilitation may mitigate these negative factors and assist in improving strength and function prior to a surgical intervention. This may include exercise, patient education, pain management and psychological support.

Researchers from Anglia Ruskin University (ARU), Addenbrooke’s – Cambridge University Hospitals NHS Foundation Trust (CUH) and Western University in Ontario, Canada, examined the results of 48 unique clinical trials involving prehabilitation techniques such as exercise, pain management and acupuncture among patients about to undergo orthopaedic surgery.

Outcomes were measured prior to surgery as well as at intervals post-operation. Results were graded for certainty, or confidence that results were true.

Prior to surgery, the study found strong evidence that prehabilitation led to a reduction in back pain for people waiting for lower back surgery and evidence of moderate certainty for improvement in their health-related quality of life.

For patients waiting for total knee replacement, evidence of moderate certainty showed prehabilitation improved function and muscle strength. For patients waiting for a total hip replacement, evidence of moderate certainty showed prehabilitation improved health-related quality of life and hip muscle strength.

Following an operation, the study found that prehabilitation improved function in the short to medium term compared with no prehabilitation. In particular, evidence of moderate certainty suggested prehabilitation had favourable outcomes on function in those who had undergone knee replacement surgery at six weeks post-operatively. Evidence of moderate certainty also suggests prehabilitation improved function six months after lower back surgery.

Lead author Anuj Punnoose, ARU PhD candidate and Clinical Specialist Physiotherapist at CUH, said: “This study stemmed out of a need to find the best ways to prepare orthopaedic patients prior to surgery and prevent them from further deconditioning. Furthermore, any prehabilitation programme should ideally be delivered for at least four to six weeks prior to the surgical intervention and twice a week for optimum results. Health services looking at developing such programmes could utilise recommendations from this study.”

Source: Anglia Ruskin University

How the Influenza Virus Hijacks Our Cells’ Mechanisms

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Influenza epidemics, caused by influenza A or B viruses, result in acute respiratory infection. New research published in published in the journal PNAS has identified how the influenza A virus manages to penetrate cells to infect them. By attaching itself to a receptor on the cell surface, it hijacks the iron transport mechanism to start its infection cycle. By blocking the receptor involved, the researchers were also able to significantly reduce its ability to invade cells. These results highlight a vulnerability that could be exploited to combat the virus.

Influenza viruses represent a major risk to human and animal health. Their potential for mutation makes them particularly elusive. ”We already knew that the influenza A virus binds to sugar structures on the cell surface, then rolls along the cell surface until it finds a suitable entry point into the host cell. However, we did not know which proteins on the host cell surface marked this entry point, and how they favoured the entry of the virus,” explains study leader Mirco Schmolke, Associate Professor at University of Geneva (UNIGE).

A receptor as a key to infection

The scientists first identified cell surface proteins present in the vicinity of the viral haemagglutinin, the protein used by the influenza A virus to enter the cell. One of these proteins stood out: transferrin receptor 1. This acts as a revolving door transporting iron molecules into the cell, which are essential for many physiological functions.

“The influenza virus takes advantage of the continuous recycling of the transferrin receptor 1 to enter the cell and infect it,” explains first author Béryl Mazel-Sanchez, a former post-doctoral researcher in Mirco Schmolke’s lab. “To confirm our discovery, we genetically engineered human lung cells to remove the transferrin receptor 1, or on the contrary to overexpress it. By deleting it in cells normally susceptible to infection, we prevented influenza A from entering. Conversely, by overexpressing it in cells normally resistant to infection, we made them easier to infect.”

Inhibiting this mechanism

The research team then succeeded in reproducing this mechanism by inhibiting the transferrinreceptor 1 using a chemical molecule. ”We tested it successfully on human lung cells, on human lung tissue samples and on mice with several viral strains,” says Béryl Mazel-Sanchez. ”In the presence of this inhibitor, the virus replicated much less. However, in view of its potentially oncogenic characteristics, this product cannot be used to treat humans.” On the other hand, anti-cancer therapies based on the inhibition of the transferrin receptor are under development and could also be interesting in this context.

”Our discovery was made possible thanks to the excellent collaboration within the Faculty of Medicine as well as with the University Hospitals of Geneva (HUG) and the Swiss Institute of Bioinformatics (SIB),” the authors add. In addition to the transferrin receptor 1, scientists have identified some 30 other proteins whose role in the influenza A entry process remains to be deciphered. It is indeed likely that the virus uses a combination involving other receptors. ”Although we are still far from a clinical application, blocking the transferrin receptor 1 could become a promising strategy for treating influenza virus infections in humans and potentially in animals.”

Source: Université de Genève

New Compound Secreted by Bacteria Speeds up Healing

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Complicated, hard-to-heal wounds are a growing medical problem and there are currently only two drugs approved with proven efficacy. A new study published in eClinical Medicine shows that treatment with a specific type of modified lactic acid bacteria works well and has a positive effect on the healing of wounds.

Previously, the researchers had demonstrated accelerated wound healing after topical treatment using lactic acid bacteria (Limosilactobacillus reuteri) genetically modified to produce the chemokine CXCL12 (ILP100-Topical).

Now, in their first clinical study on humans, the researchers established safety and tolerability. Other objectives were to see clinical and biological effects on wound healing using traditionally accepted methods, as well as more exploratory and traceable measurements.

36 healthy volunteers were included in the study with a total of 240 induced wounds studied. The study’s design and methodology are described in more detail below.

The results show that treatment using ILP100-Topical was safe and well tolerated among all individuals and doses, and neither ILP100 nor CXCL12 could be detected in locations beyond the wounds. A significantly higher proportion of healed wounds (p=0.020) was seen on day 32 using multi-dose ILP100-Topical compared to saline and placebo (76% (73/96) and 59% (57/96) healed wounds respectively) when the results from the multi-dose-treated wounds were pooled. In addition, the time to first recorded healing was reduced by an average of 6 days, and by 10 days at the highest dose. The mechanism of action of ILP100-Topical was also confirmed when the treatment resulted in increased CXCL12-positive cells in the wounds, as well as increased blood flow around the wounds during the healing phase.

“Our study shows that bacteria modified to produce and deliver human protein for local effects can be used as drugs to accelerate the healing of wounds. This is the first time this has been shown in controlled human studies, and it can be expected that the effect is greater in patients with diseases that negatively affect wound healing,” explains Mia Phillipson, Professor at the Department of Medical Cell Biology at Uppsala University.

The favourable safety profile and the beneficial effects on wound healing observed here support further clinical development of ILP100-Topical for the treatment of complex and hard-to-heal wounds in patients, which is already under way.

Many immune-active proteins are inherently unstable and degrade quickly, so supplying them from lactic acid bacteria to the exact site of action is one way to develop them as drugs.

“The potential is really endless when you consider how important a role proteins play in various processes in the body, and how many diseases we currently do not have good enough treatments for. We have already produced another drug candidate to cure and reduce inflammation in the gut of cancer patients – ILP100-Oral – and in the future we will start a research project with another chemokine for the treatment of lung diseases,” concludes Phillipson.

Source: Uppsala University

Ischaemic Heart Disease in the Elderly Linked to Increased Dementia Risk

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Older people with ischaemic heart disease have an increased long-term risk of dementia and accelerated cognitive decline. Recent research in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association suggests that the heart, the brain, and cognitive function are all connected in the ageing process. Appropriate prevention and treatment of ischaemic heart disease in older people might reduce the burden of dementia, the researchers suggest.

The researchers regularly followed a cohort of 2568 older people aged 60 years or older, without dementia at baseline and living in Stockholm, from 2001–2004 through 2013–2016. Heart diseases at the study entry were ascertained via clinical examination and linkage to the Swedish National Inpatient Register. Dementia status and cognitive function during the follow-up period were diagnosed and assessed regularly following the standard approaches.

“We used statistical methods to link ischemic heart disease at the study entry to an increased risk of dementia and a faster decline in cognitive function during the follow-up period”, says Chengxuan Qiu, at the Department of Neurobiology, Care Sciences and Society, Division of Aging Research Center (ARC) and one of the authors of the study.

Explore cognitive trajectories

Future works should explore cognitive trajectory following the onset of ischemic heart disease and further investigate to what extent medical treatments of ischemic heart disease may affect cognitive decline and dementia onset.

The SNAC-K project on which this study is based is supported by the Swedish Ministry of Health and Social Affairs. This study is supported by additional grants from the Swedish Research Council (VR), FORTE and STINT.

A Simple Tweak to Breakfast may Help Glycaemic Control in T2D

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Research suggests that a simple tweak to the breakfast menu might help people living with Type 2 diabetes (T2D) better control their blood sugar levels. The study, published in the American Journal of Clinical Nutrition, confirms that switching from a traditional Western-style low-fat breakfast, like oatmeal, toast and fruit, to a low-carb meal higher in protein and fat, like eggs with bacon or cheese, can help people with T2D better manage their blood sugar for most of the day.

Dr Barbara Oliveira conducts research with Dr Jonathan Little’s Exercise, Metabolism and Inflammation Lab in UBCO’s Faculty of Health and Social Development. “We’re not talking about a complete diet overhaul,” says Dr Oliveira. “One of many complications for people living with T2D is rapid or large increases in blood glucose levels after a meal. Our research indicates a low-carbohydrate meal, first thing in the morning, seems to help control blood sugar throughout the day.”

Controlling glucose levels is critical for reducing the complications of T2D including inflammation and cardiovascular disease – the major cause of morbidity in patients with T2D.

“Treatment strategies that can help lower post-meal glucose swings and rapid changes in glucose are crucial to managing this condition,” she adds. “We’ve determined that if the first meal of the day is low-carb and higher in protein and fat we can limit hyperglycaemic swings.”

Low-carb diets have become trendy in recent years and have been recognised as a dietary strategy to improve glucose control, Dr Oliveira explains. However, similar to all diets, it’s tough to follow, especially long term. Instead of asking patients to commit to every meal being low-carb, she and Dr Little examined the idea of making just the first meal of the day low-carb to see how that impacts diet adherence, and more importantly, blood glucose levels.

Their 12-week study had 121 participants split into two groups. One was advised to eat from a selection of low-carb breakfasts containing approximate amounts of 8g of carbohydrate, 25g of protein and 37g of fat while the other was advised to eat from a selection of low-fat higher-carb options containing about 56g of carbohydrates, 20g of protein and 15g of fat. All the breakfast options in both groups provided 450 calories.

Participants had a variety of breakfast choices and were required to upload a photo of their meal, which was reviewed by a study dietitian to confirm compliance.

All participants were provided with a continuous glucose monitoring device they wore throughout the study and A1c blood tests were done, before and after the 12 weeks. They also measured their weight and waist circumference at the beginning and end of the trial. As the study continued they reported feelings of satiety, energy and activity levels.

Dr Oliveira notes while there were no significant differences between the low-carb and other group for weight, body mass index or waist circumference, the low-carb group did see a reduction in blood sugar levels and some were able to reduce their glucose-lowering medication. The upward and downward swings in blood glucose levels, known as glycaemic variability, with the low-carb group was also significantly lower, suggesting the benefits of a low-carbohydrate breakfast for stabilizing blood sugars throughout the day.

One additional interesting finding was that people who had the low-carb breakfast self-reported lower calorie and carbohydrate intake at lunch and during the remainder of the day. This could suggest that a breakfast rich in fat and protein, while lower in carbs, can impact daily eating habits.

“Having fewer carbs for breakfast not only aligns better with how people with T2D handle glucose throughout the day, but it also has incredible potential for people with T2D who struggle with their glucose levels in the morning,” she adds. “By making a small adjustment to the carb content of a single meal rather than the entire diet, we have the potential to increase adherence significantly while still obtaining significant benefits.”

Source: University of British Columbia