August 2021 - Inserm Newsroom

ComPaRe study: one in twelve patients hesitant to be vaccinated changes their mind after consulting information on the benefits and risks of vaccines

Posted on August 11, 2021November 23, 2022 by Graziella Cara

©Adobe Stock

The team from the Clinical Epidemiology Center of Hôtel-Dieu AP-HP Hospital, Inserm and the University of Paris, coordinated by Professor Philippe Ravaud, has developed an online tool for viewing the benefits and the risks of vaccination against Covid-19. Presented to a sample of chronic patients from “ComPaRe”, the Community of Patients for Research created by the AP-HP and the University of Paris, the team measured how many of them, previously undecided about their vaccination, have changed my mind after using the tool. This work was published on July 31, 2021 in BMC Medical Informatics and Decision Making.

Convincing the hesitant population to get vaccinated is a matter of major concern in the fight against the Covid-19 epidemic.

According to a study recently published in the Lancet Public Health ¹ , around 30% of adults in France would categorically refuse the COVID-19 vaccination, and 9 to 40% are hesitant. The main reasons for refusing vaccination are concern and demand for further hindsight regarding the safety and efficacy of vaccines.

In January 2021, the team from the Clinical Epidemiology Center of Hôtel-Dieu AP-HP Hospital, Inserm and the University of Paris, developed an online tool measuring the benefit / risk of vaccination. In particular, it makes it possible to visualize the risk of death, hospitalization and long-term COVID with and without vaccination, as well as the serious adverse effects of vaccination, depending on the age and sex of the person.
The data used come from published scientific publications, freely accessible on the internet. The data concerning the efficacy and safety of the vaccines which were used to construct the tool come from the clinical trials which led to their marketing authorization.

3,152 patients from the Community of Patients for Research (ComPaRe) participated in the evaluation of this tool. The research team asked participants to indicate their intention to be vaccinated before and after viewing the tool. By comparing patient responses before and after, she was able to determine the influence that visualizing the benefits and risks of vaccines could have on patient decisions.

Before consulting the tool, 1,952 (62%) patients declared that they wanted to be vaccinated, 961 (30.5%) preferred to wait until they had more information on the efficacy and safety of vaccines before being vaccinated and 239 (7.5%) did not want to be vaccinated.

After consulting the tool, 96 of the 1,200 people initially reluctant to vaccinate had changed their minds. On average, for every 12 people reluctant to get vaccinated, one person changed their mind after consulting the tool.

The tool has been online on the government website since May 2021 . Used by more than 125,000 people, it has been updated with data from the Janssen vaccine and supplemented with data on the risk of thrombosis after the AstraZeneca vaccine.

Created in 2017 by the AP-HP and the University of Paris, ComPaRe, the Community of Patients for Research today brings together nearly 45,000 patient volunteers across France.

On this occasion, ComPaRe renews its call for participation in order to bring together 100,000 patients to contribute online to medical research on its compare.aphp.fr site .

Participants help advance research on their chronic disease (s) by regularly participating in scientific studies and answering researchers’ questions via the secure platform https://compare.aphp.fr .

Patients participate in the general cohort and / or one of the 13 cohorts dedicated to diabetes, Verneuil’s disease, vitiligo, chronic low back pain, kidney disease, vasculitis, arterial hypertension, endometriosis, asthma, COPD, Marfan syndrome, neurofibromatosis and long Covid.

And new cohorts are being formed.

1 – https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(21)00012-8/fulltext#%20

Vaccination Covid-19 et populations particulières : une grande étude de cohorte pour orienter les recommandations destinées aux plus fragiles

Posted on August 9, 2021November 23, 2022 by Tatiana Marotta

The appendix is not an unnecessary organ but is in fact correlated with a longer lifespan

Posted on August 3, 2021November 23, 2022 by Graziella Cara

The appendix is an anatomical structure that can be found in a wide range of very different species, from the orangutan to the koala, beaver, and of course humans. © David Clode /Unsplash

Long considered an unnecessary organ, the appendix is now the focus of several studies that aim to better understand its role. Present in many mammals, including humans, it appears to have developed at least 16 times over the course of the evolutionary history of mammals, suggesting that its function must confer a positive selective advantage on those that have it. A new study carried out by researchers from Inserm and the French Museum of Natural History suggests that the presence of the appendix is in fact correlated with greater longevity. Their findings have been published in the Journal of Anatomy.

The appendix is a small anatomical structure of a few centimeters in size, located in the abdomen and attached to the colon, the function of which has long been poorly understood. According to the theories of Charles Darwin, the appendix was a vestigial structure, useless and devoid of function. It might even be seen as potentially dangerous to health due to the risk of inflammation of the organ. If such inflammation, known as “appendicitis,” is left untreated, it can develop into peritonitis and result in death.

Over the last few years, researchers have sought to learn more about the role of the appendix. Studies have, for example, shown that an appendectomy performed in cases of confirmed appendicitis before the age of 20 has a protective effect against the onset of a particular form of chronic inflammation of the colon and rectum: ulcerative colitis.

Researchers have also shown that the appendix is not only present in humans. It first appeared in mammals at least 80 million years ago, and over the course of evolution has developed independently multiple times in several mammalian lineages, with no obvious correlation with diet, social life, or the environment. Today it can be found in a wide range of animals: from orangutans and koalas to manatees, beavers, and platypuses. Its function has however remained a mystery, with no study reaching a definitive conclusion.

A link with mammalian longevity

The team led by Inserm researcher Eric Ogier-Denis and his colleague Michel Laurin from the French Museum of Natural History approached the question by analyzing data from 258 species of mammals, 39 with and 219 without an appendix. The scientists focused in particular on the theoretical maximum longevity (the theoretical lifespan of mammals, established based on their weight) and actual maximum longevity of the various species considered.

They have shown for the first time that the presence of the appendix is correlated with an increase in the maximum longevity observed for a species. Compared to mammals of the same weight without an appendix, mammals with an appendix have a longer lifespan.

“The idea of focusing on longevity developed from our work on the relationship between appendicitis/appendectomy, ulcerative colitis and the involvement of the immune system. A more active and better educated immune system should theoretically provide greater resistance to the environment and a longer lifespan. We therefore tested this hypothesis by partnering with two internationally renowned evolutionary experts from the French Museum of Natural History. This is the first time the existence of a correlation between the presence of the appendix and a trait in the life history of mammals has been demonstrated,” explains Eric Ogier-Denis.

The team has also shown that the appendix has developed at least 16 times and has only been lost once (by the lemur Hapalemur griseus, endemic to Madagascar) during the evolutionary history of mammals, which supports the idea that

through its function this organ provides a significant positive selective advantage with regard to the laws of natural selection.

A bacterial sanctuary

The researchers believe that the most likely hypothesis to explain the link between the presence of the appendix and longevity is that the shape of the organ enables the development of a selective “bacterial sanctuary” that reduces mortality from infectious diarrhea by promoting rapid recolonization of bacterial species that are essential to the host. The presence of the appendix would therefore be associated with a decrease in mortality and thus greater longevity in mammals that have this organ.

“This does not mean that an appendectomy performed on a human to treat appendicitis has an effect on longevity. Appendicitis at a young age is clearly beneficial by strengthening the education of the immune system and enabling it to fight any subsequent infection more effectively. The treatment for appendicitis remains appendectomy and this work does not provide any evidence to suggest this treatment approach should be changed. Only an appendectomy performed in a patient without appendicitis might have harmful consequences in the context of inflammatory and infectious bowel disease,” explains Eric Ogier Denis.

This work therefore opens up clear new avenues of research for elucidating the controversial issue of the function of the appendix. Over the coming months, the researchers will build on it with field studies looking at different species of mammals to confirm the link between the appendix and longevity.

Diabetes: Study Of Satiety Mechanism Yields New Knowledge

Posted on August 2, 2021November 23, 2022 by Graziella Cara

In purple, the tanycytes that form the brain’s cellular gateway to the hormone leptin; in yellow, the appetite-inducing neurons and, in blue, the appetite-suppressing neurons. Leptin targets both neuron types, inhibiting the former and using its appetite-suppressant signal to activate the latter. © Vincent Prévot

Diabetes, a disease in which blood sugar levels remain too high for too long, can lead to health complications in the long term. Type 2 diabetes (T2D) accounts for 90% of cases. Patients are usually obese or overweight, with risk factors that include sedentary lifestyle and unbalanced diet. To increase their understanding of the disease, a team of researchers from Inserm, Université de Lille, and Lille University Hospital in the Lille Neuroscience and Cognition laboratory[1] has for several years studied the role of leptin, a hormone involved in appetite control that sends satiety signals to the brain. In a new study published in the journal Nature Metabolism, in addition to furthering scientific knowledge of the mechanism of satiety, the scientists developed a new mouse model of diabetes that will be useful for and relevant to future research in this area.

Leptin, the satiety or appetite-suppressant hormone, is secreted by the adipose tissue at levels proportional to the body’s fat reserves and regulates appetite by controlling the feeling of fullness. It is transported to the brain by tanycytes – cells which it enters by attaching to the LepR receptors. Tanycytes are therefore leptin’s gateway to the brain, helping it to cross the blood-brain barrier and deliver satiety information to the neurons.

Previous research has revealed that such transport is impaired in subjects who are obese or overweight. This goes some way to explaining their dysfunctional appetite regulation given that it is more difficult for the information on satiety to reach the brain. In their new study, the researchers took a closer look at this transport mechanism, and more precisely the role played by the LepR receptors.

The key role of satiety hormone receptors in glucose management

In mouse models, the researchers removed the LepR receptor that is located on the surface of the tanycytes. After three months, the mice experienced a marked increase in their fat mass (which doubled over the period) as well as a loss of muscle mass (reduced by more than half). The total amount of weight gained was only fairly moderate. The scientists also regularly measured the animals’ blood sugar levels following the injection of glucose.

They found that in order to maintain blood sugar at normal levels (between 0.70 and 1.10 g/L), the mice secreted more insulin during the first four weeks of the experiment. Three months after removing the receptor, their ability to secrete insulin from the pancreas appeared to be exhausted.

Removing the LepR receptors and impairing leptin transport to the brain therefore led the mice to initially develop a pre-diabetic state. This occurs when the body releases more insulin than usual in order to control blood sugar. Then, in the longer term, the mice became unable to secrete insulin and as such unable to control their blood sugar levels. These data therefore suggest that impaired leptin transport to the brain via the LepR receptors plays a role in the development of type 2 diabetes.

In a healthy animal or person, blood sugar levels rise slightly after the ingestion of glucose and then decrease rapidly. In order to bring blood sugar back to within normal limits, the pancreas secretes insulin that helps the glucose to penetrate the body’s cells.

In animals deprived of the LepR receptor where leptin enters the brain, blood sugar levels are abnormally high in the fasting state and even more so after ingesting glucose. The pancreas becomes unable to secrete the insulin needed for the body to absorb the glucose. The brain’s “deafness” to the information conveyed by leptin thereby renders the pancreas ineffective.

In the last part of their research, the scientists reintroduced leptin to the brain and observed the immediate resumption of its pancreatic function-promoting action – particularly the ability of the pancreas to secrete insulin to regulate blood sugar. The mice quickly regained a healthy metabolism.

This study therefore elucidates the brain’s role in type 2 diabetes and also helps to further research into a disease that until then had not been considered to involve the central nervous system.

“We show that the brain’s perception of leptin is essential for the management of energy homeostasis[2] and blood sugar. We also show that blocking the transport of leptin to the brain impairs the functioning of the neurons that control pancreatic insulin secretion,” concludes Vincent Prévot, research director at Inserm and last author of the study.

Another interesting finding of this study: by removing the LepR receptor where leptin enters the brain, the animal model obtained exhibits the characteristics of so-called East Asian Diabetes, still little studied by researchers. This diabetes phenotype mainly affects the populations of Korea and Japan.

While so-called Western Diabetes is mainly associated with people who are markedly overweight (BMI >25) or morbidly obese (BMI >30), this other type 2 diabetes phenotype is often associated with people who are slightly overweight, have increased levels of abdominal fat, and insulin insufficiency related to deficient insulin secretion by the pancreas.

According to the scientists, the development of this new animal model will make it possible to further research into this disease that affects millions of people.

The research team started by describing the mechanism by which leptin passes through the cell gate: tanycytes (Figure opposite: cells in yellow). These cells capture circulating leptin from the blood vessels which at that location have the particularity of letting it through (step 1). Whilst in the tanycyte, the leptin captured by LepR activates the EGF receptor (or EGFR) which itself activates an ERK signaling pathway (step 2), triggering its release into the cerebrospinal fluid (step 3). The leptin then activates the brain regions that convey its anorectic (appetite suppressant) action, as well as control of pancreatic function (step 4).

[1] This research was performed in collaboration with two laboratories at Institut Cochin and Université de Strasbourg as part of a project funded by the French National Research Agency (ANR) and two European laboratories, one at Lübeck University in Germany and the other at the University of Santiago de Compostela in Spain, within the framework of European Community funding. In addition, the Lille Neuroscience and Cognition laboratory is a member of LabEx EGID (European Genomic Institute for Diabetes) and DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer’s disease).

[2] Stabilization, regulation in living organisms, of certain physiological characteristics (food intake, energy expenditure, etc.).

Inserm Newsroom - Press room of the French national institute of health and medical research

Month: August 2021