British drug 70% decreased the growth of aggressive tumors

Bertoneri in combination with chemotherapy affects the DNA of cancer cells, not allowing her to recover.

Photo: depositphotos.com

Specialists from the Institute of cancer research UK are looking for new ways to fight cancer. British scientists have focused on the ability of cancer cells to restore DNA. In the course of studies has identified the ATR protein, which is responsible for the repair of cells, which were exposed to the drug personaltab. Scientists did not expect so much positive effect, because the British drug in combination with chemotherapy 70% decreased the growth of aggressive tumors. Experts believe that made a breakthrough in the treatment of severe forms of cancer, because patients with such diagnoses have experienced a new drug.

The success of the operation personeria is that chemotherapy also affects the DNA of tumors makes them more sensitive to the ingredients of the new drug. To date, the side effects of the drug are mild and do not go to any comparison with the benefit from personaltime. Scientists are going to continue to create tools that act on the DNA of cancer tumors.

Kartashov Timur

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Listening cells, Covid-19 distress is released at the end of the phone

► Ile-de-France Psychology Unit: “Confined, I no longer recognize the one I married …”

At the start of the afternoon, Annie picks up her phone because anxiety is eating her away. “I’ve been retired for a few weeks, she says. In the space of two months, I went from days where I worked 8 hours a day to this situation of confinement alongside my depressed husband. He has been treated for years. Meeting me around the clock is complicated. I no longer recognize the man I married. “

Next call. Sonia feels a big void. “I am alone in my apartment and I understand that I don’t know anyone anymore. I only worked, she explains. Whose news is it from? “

→ LIVE. Coronavirus: the latest news in France and worldwide

Raffaela Cucciniello answers. This psychologist co-hosts the network of listeners of the Psy Ile-de-France call number, ordered by the Regional Health Agency to support the relatives of patients suffering from mental disorders. For everyone, containment has brought about “Of very deep existential questions, she testifies, which is not always easy to answer. ” This toll-free number could be made permanent after deconfinement, according to Doctor Raphaël Gourevitch, head of psychiatric emergencies in Sainte-Anne.

► Listen to family news of Apprentis d’Auteuil: “I think I’m going to stick it against the wall”

Another line, same distress. Corinne called the government’s toll-free number, which redirected her to the Apprentis d’Auteuil family information line. This forties tells the story “Burnout” who is watching. ” I can not stand it anymore. My husband and I are telecommuting. I also have to take care of my three children. The eldest is in middle school but I have to help the other two, in elementary school, with their homework. I find myself managing everything: work, meals, homework. I am caught 24 hours a day! “, she explodes. At the end of the phone, Marie-Pierre Francis tries to appease him. ” Take a break. Do you go out for an hour a day for a walk in the neighborhood? You have the right, you know. “

16 hours. Christophe’s voice trembles. “I think I’m going to stick it against the wall. “ The divorced father is confined with his 16-year-old son, who usually lives with his mother. “He doesn’t care, he’s cheeky, rude. Normal, my ex passes everything to him “, coward Christophe. For 45 minutes, he pours out a torrent of words which combine sorrow, regrets, rage also against his divorce, his own story. The listener cashes in and then ends up asking if there is really nothing this son can do. “If of course, it has nice sides”, agrees Christophe. In small touches, the professional then suggests to value these good sides. Above all, it gives the direct number for Family Info Listening ” in case “, as well as that of the nearest child welfare office.

► Catholic listening cell: “Am I not going to go to hell? “

Chantal, member of the chaplaincy of a hospital grouping in central France, has just started this Thursday her permanence for the toll-free number set up by the episcopate and the Conference of men and women religious of France. At the other end of the line is a woman with a sad voice. She can only see her 96-year-old mother for ten minutes every other day at an Ehpad window. ” It’s very, very hard She sighs, asking if a chaplain could come and see her. Chantal gives her the coordinates of the local chaplaincies.

Visibly happy with this suggestion, the woman confides more: I sometimes read the Gospel to Mom, but I am unprofessional. “” But it’s already a lot that you can share your faith, encourages Chantal. But maybe you also call a little for yourself. It’s probably not easy to have your mother in a nursing home… Are you an only child? The woman has a brother who is not very present. “ I feel guilty for placing Mom in Ehpad. This is not what I would have liked. “

Another call from a woman, mother of a 23-year-old disabled son, placed in an institution. ” I haven’t been able to go see him since the confinement. I call him regularly, but what does he understand about the situation? “This woman opens up more about her son:” I am alone to assume it, his father could not bear to take care of it, he was mistreating with his son … We are in the process of divorce. But with containment, everything is stopped ” Chantal gives her the number of a local relay and suggests that she pray together.

It is also on Thursday that Marie-Claire holds her permanence for the toll-free number of CEF-Corref. A man calls, in great dismay at the confinement : “It’s too hard, it’s too long, I’m not made for that, I need to hear someone “, He launches, before wondering:” What is the use of praying, practicing every Sunday as I was taught during my childhood ? I know God is love but I don’t feel anything “He continues, acknowledging that he” calls everything into question

Geneviève, mother and grandmother, belongs to a listening network in her city and joined that of the 280 listeners of the Catholic Church. One evening during Holy Week, an elderly lady, sobs in her voice, told her that she was afraid. ” I will not be able to meet a priest to confess before Easter or to do the Chemin de croix, when I’ve always done it like that. Am I not going to go to hell?

► Protestant listening cell: “It’s been a week since I last formulated a sentence …”

The voice is quavering in the handset. “My 82-year-old husband just died from Covid-19. I feel so alone after 57 years of marriage… I hardly see anyone, apart from my son who comes to drop off some groceries in the evening, wrapped in his protective gear ”. Miles away, the reformed pastor Jean-Louis Massot, hospital chaplain in Poitiers (Vienne) and listening to the cell of the Federation Protestante de France (FPF), searches for the right words. At the end of the line, the lady is gradually revealed: “I was born into a Catholic family, but I strayed from the faith because of all the speeches heard, child, on hell, the devil, sin …” The chaplain offered to entrust her to God, and to recite an Our Father.

Many callers report immense loneliness. “Hello, is that the Protestant Church? Can i talk to you? It’s been a week since I last formulated a sentence … ” This time, it is Pastor Brice Deymié, national chaplain of the prisons of the FPF, who picks up. The interlocutor, in his fifties, has a great need to speak but does not really know where to start. Gently, the pastor leads him to tell about his daily life: “You see, every morning, I do these little morning rituals … Here, I open my shutters”, he begins to describe. At other times, there is silence …

While the detainees are denied visits, the latter coordinates the Protestant “hotline” established on April 27 in the prisons. “This morning, I got up, I waited for breakfast … I’m here, I am waiting, and time is passing even more slowly than usual”, tells him a prisoner. Brice Deymié takes the time to comfort him: he feels that the individual, probably without family, is looking for “Listening in a peaceful voice, outside that of the supervisors.”

► Muslim cell: “I found my patient, Muslim, dead at his home …”

Like the other “hotlines”, the French Council for Muslim Worship (CFCM) system was set up to respond, 24 hours a day, to the needs and questions of the confined. Many relate to mortuary cleansing, the repatriation of bodies, or the burial of the deceased in denominational squares.

“I’m a liberal nurse, I just went to a Muslim patient’s house and I found him dead. I am not a Muslim myself, but I am calling you because this man has no family, what should I do? “ Febrile, the young nurse, visiting Seyne-sur-Mer (Var), needs a pragmatic response. “You must call our regional office, they can guide you to find solutions for the burial”, redirects the listener Fathia El Moumni, chaplain of hospitals in the Occitania region: “All the families and loved ones in mourning, we must tell them how much we are there for them …”

► Jewish listening cell: “Why did he die? “

At two in the morning, the voice of a man, married and father, resounds in the earpiece: “My father, 82, died of the coronavirus. My mother also caught her, she is hospitalized but saved … I don’t know what to do for my father’s body. Mr. Rabbi, my father was someone very pious, diligent in the synagogue, why did he die? “

In the middle of the night, Bruno Fiszon, chief rabbi of Metz (Moselle) and hospital chaplain, first advises him on the funeral. But a few days later, the two men remember. “God takes back even the best. We must remain in the hope of eternal life “, he sees himself answering him, convinced by hanging up that the “This man’s traditional faith will allow him to overcome the ordeal.”

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Is it true that nicotine users contract Covid-19 less?

Hello,

Numerous case studies demonstrate this unequivocal : smokers who get Covid-19 have a risk greatly increased to develop severe forms of the disease. In this work, we find that the proportion of smokers is two to four times higher in severely ill patients than in those with a moderate form of the disease.

On the other hand, several publications relayed since the beginning of April report a counterintuitive phenomenon: in several countries, the proportion of smokers infected with SARS-CoV-2 would be lower than the proportion of smokers at regional or national level. The Minister of Health, Olivier Véran, recently mentioned this data.

In France, works being published conducted on a limited number of patients at the Pitié-Salpétrière, as well as a study in a school environment in Crépy-en-Valois (prepublished this April 23), also reported this statistical trend.

Many potential limits

Note now that the link between smoking status and propensity to be infected does not appear in all research. So in a recent study published in the Jama, involving 5,700 New York patients hospitalized for Covid-19, the proportion of smokers was analogous to that observed in the regional population.

The first studies were met with skepticism, not without reason. Indeed, many of these works have sometimes significant biases.

First limitation present in all studies (with the exception of French studies): the age parameter of hospitalized patients. Indeed, a significant proportion of patients with severe forms of Covid-19 are over the age of 65. The prevalence of smokers decreases very strongly with age (for example, in France, 65-75 year olds smoke 2.5 times less than the general population).

In the study conducted at Pitié-Salpêtrière, taking into account the age and sex of the patients, smokers nevertheless appeared to be four times less likely than non-smokers to be Covid +. A rate observed both in hospitalized patients and in patients treated on an outpatient basis. However, in order to draw more solid conclusions, these results should have been put into perspective with the smoking profile of patients who usually attend this hospital, at the same periods in previous years.

Another parameter that seems to be excluded from most analyzes: the socio-economic profile of the groups studied, which can strongly influence the expected proportion of smokers. A limitation mentioned by the authors of the French study, who established their calculations “Assuming that the population studied who lives in a limited area around a Parisian hospital has the same smoking habits as the French population in general”, and who note that “Healthcare workers were overrepresented in the outpatient group due to routine workplace testing when they became symptomatic”. The study conducted at Crépy-en-Valois seems to take this parameter into account. And its results are consistent with the Pitié Salpêtrière study.

Third important pitfall: the quality of the information collected is not always there … far from it. In some studies used by epidemiologists to conduct their analyzes, the smoking status of the sickest Covid + patients was simply not informed. Commentators have also noted that one of these studies considered individuals to be “non-smokers” less than 30 packages per year – preventing any comparison with national statistics which relate to all cigarette consumers.

For its part, the study conducted at Pitié-Salpêtrière seems to consider as “former smoker” any person who had quit smoking at the time of his hospitalization … without mentioning the hypothesis that patients may have stopped smoking because of the first Covid-19 symptoms! A point which would considerably influence the results. Requested by CheckNews, Zahir Amoura, author of this work, has not yet commented on this point.

Is the phenomenon biologically plausible?

The interpretation of these statistics, as well as the extent of the associated phenomenon, are still questionable.

Researchers, however, have begun to explore the hypothesis of a direct causal link between smoking status and primary SARS-CoV-2 infection. The question arises indeed: from a physiological point of view, is it plausible that lungs exposed to tobacco are less permeable to this coronavirus? Could nicotine be involved in the phenomenon?

A possible link with the ACE2 receiver?

SARS-CoV-2 infects cells by binding to the ACE2 receptor, abundant on the surface, in particular, the cells of the mucous membranes and the alveolar pulmonary tissue. The expression of the gene corresponding to ACE2 is not identical in smokers and in non-smokers. Based on animal models, smokers have long been considered to express less ACE2 – which suggests a simple explanation for the phenomenon: less ACE2 induces a lower propensity for infection.

But recent data, which seem to be corroborated by new researchsuggest that in humans, smoking is associated with a higher expression of ACE2. A higher propensity for coronavirus infection would therefore be expected. The epidemiological observations mentioned above, suggesting a protective effect of tobacco, would therefore raise a paradox.

Several explanatory hypotheses have been formulated. Some authors have advanced that in all patients, infection with SARS-CoV-2 would decrease the availability of ACE2 receptors in the lungs. The biological processes that usually mobilize these receptors would be hindered, leading to various symptoms of the disease. People with more ACE2, even if they were infected, would develop fewer symptoms. However, this interpretation is challenged by the Crépy-en-Valois study, where the diagnosis of infection was made on a blood test, and not on a simple clinical assessment of symptoms.

According to other works, the nAChR nicotinic receptor could modulate the activity of ACE2. Could stimulating nAChR make infection through ACE2 more difficult? This fact is not yet proven. “The possibility of a reciprocal modulation between ACE2 and the nicotinic receptor is an interesting scientific question for which we have no answer”, insists Professor Jean-Pierre Changeux, co-author of a scientific article inviting this hypothesis to be explored.

La Pitié-Salpêtrière has announced the launch of several clinical trials in this direction. The first, conducted on caregivers, aims to compare the infection rate between a group carrying nicotine patches and a group carrying placebos patches. More trials need to be done on Covid + patients in hospital to assess whether nicotine affects the course of the disease – especially in smokers who are forced to quit as a result of hospitalization.

Nicotine and vaping: preliminary data not very encouraging

The return of associations of electronic cigarette users does not seem to go in this direction, however. According to the analysis of a questionnaire sent in early April to several thousand members of the AIDUCE and SOVAPE associations, the rate of patients suspected of being Covid + was similar whether or not there was nicotine consumption – around 2.5 %. “Although it concerns nearly 10,000 people, this citizen survey is inconclusive on a major protective effect of nicotine, note the associations in a press release. The first data show no major positive or negative effect of vaping when faced with the risk of contracting Covid-19 for vapers and their entourage. ”

Tobaccoologist Bertrand Dautzenberg, who had encouraged these associations to explore this hypothesis, notes on Twitter that the data was not collected under conditions “Respecting all the obligations of scientific studies”. He nevertheless considers that they are not showing strong signs of a beneficial effect of nicotine in reducing Covid-19 levels. ” He invites an analysis of the Health Database to further explore this hypothesis.

No reason to start smoking

The tobacco specialist recalls “That tobacco certainly brings a negative effect greater than that of a small benefit which is not confirmed at all”. “This leads to encouraging all doctors to advise and support smoking cessation for all smokers.” The authors of the Crépy-en-Valois study abound in this sense, recalling that tobacco is responsible for 75,000 deaths per year in France. “Smoking cannot therefore be offered as a way of protecting oneself against the new coronavirus”, they insist.

Unsurprisingly, this finding is similar to that of the authors of a review on the complications of Covid-19 related to smoking. “Risk factors for severe forms of Covid-19 (pulmonary and cardiovascular disorders, diabetes, etc.) are more common in smokers. Smokers with comorbidities should quit smoking by all means. ” They also observe that confinement can lead to social isolation and psychological distress that increase the need for smoking. [En outre], smoking is more prevalent among the economically less advantaged groups, and they are potentially more at risk for Covid-19. ”

For its part, the association Alliance contre le tabac urged the greatest caution with regard to speculative information in circulation. In the absence of more evidence, nicotine users, “Should not expect to be more protected than the population from the current epidemic”, she recalls. In addition, she advises non-smokers to use nicotine substitutes. A warning also formulated by the promoters of the Pitié-Salpétrière study or by the Minister of Health.

In summary

Although well publicized, epidemiological observations associating smoking and the risk of developing the symptoms of Covid-19 are difficult to interpret at this time. Under the hypothesis of a real cause and effect link, the biological mechanisms mentioned in the press are still hypothetical. None have yet been formally tested.

Listen to the weekly behind the scenes podcast of CheckNews. This week: Covid-19: what are the real figures for deaths in intensive care?

Jérôme Salomon, the Director General of Health, mentioned a mortality of 10% in intensive care of patients hospitalized for Covid-19. In this episode, Luc Peillon explains why this figure is largely underestimated.


Florian Gouthière

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Confined families: “I can no longer play dinner” – Liberation

Confined families: “I can no longer play dinner” Liberation.

Blur spots persist in the portrait of the virus

Never has a new virus been the subject of as much research, studies, analyzes as SARS-CoV-2 in such a short time. But if information has accumulated since the end of 2019, essential questions remain to try to understand what the planet is facing. At first, we imagined that it was only a simple coronavirus, like the others: a little pathogenic, fairly contagious, but relatively manageable. Everything exploded. From an infectious pathology, clinicians have discovered that it is transformed and becomes an immune pathology, even later a cardiac one. And the Covid-19 surprises with its mysteries, with more than 80% of people infected without any real manifestation, 20% with more or less important symptoms, of which 5% will go to intensive care. These proportions, for several weeks, have hardly changed. But what about the rest? Of its transmission? New symptoms? Healthy carriers? These questions still do not have complete answers. “It’s like an iceberg, we only see and we can only understand the emerged part”, tells us a member of the Scientific Council. Overview, as France begins its fifth week of containment.

How is the virus transmitted?

Friday, April 3, Anthony Fauci, director of the United States Institute of Infectious Diseases and member of the White House task force, relayed by President Donald Trump, sowed a global stir. Can the Covid be transmitted “When people are just talking”, as this respected scientist claims? “Everything takes on incredible proportions when Trump opens his mouth”, quipped Professor Xavier Lescure, an infectious disease specialist at Bichat Hospital. “An American study certainly mentioned transmission by too close discussion but if this were the case, we would have a basic reproduction rate (RO) of the coronavirus close to that of measles, smiles Karine Lacombe, head of the infectious diseases department at Saint-Antoine hospital. Clearly, each infected person could contaminate 10. We are far from it. For experts, the RO rate of Covid-19, without confinement, is rather between 2 and 3. ” Professor Lacombe insists: “The contamination is mainly done by the droplets, the cough, the sneezing, the hand-held contacts.” If the Director General of Public Health, Jérôme Salomon, also mentions contact with inert surfaces, this point remains under debate. Karine Lacombe: “On inert surfaces, we remain questionable.” Xavier Lescure, careful: “Inert surfaces are a real hidden trap, probably the forgotten link in contact transmission.”

Contagious from when and for how long?

This is a crucial point to break the dynamics of the epidemic. When and for how long should patients be isolated to stop the spread of the virus? In this area, knowledge is becoming more precise. In a study published recently in Nature, German researchers have shown that if there were traces of the virus in the patient’s larynx seven days after the onset of symptoms, the pathogen did not replicate. “It means the person is no longer contagious, says Professor Lacombe. There is a consensus that an infected person can be contagious one to two days before symptoms appear, and for seven to ten days after. “

There remains the question of healthy carriers, about 30% of all infected. As they do not cough or sneeze, their contagiousness is estimated to be very low. But it is not necessarily zero to believe the first results of an Inserm survey of 300 patients, launched in January after the first cases in Contamines-Montjoie, in Haute-Savoie: the postillions and nasal excretions of the asymptomatic contain viral particles capable of infecting other people.

What are the symptoms ?

The range of Covid-19 symptoms has unfortunately grown significantly since its arrival in Europe. If a dry cough, with fever and fatigue are the most common signals, others, which had not been reported by the Chinese, have confused infectious diseases. “It’s a shock, we didn’t see it coming, says Professor Gilles Pialoux, infectious disease specialist at Tenon Hospital. The coronavirus is the cause of neurological disorders. In some cases, this results in loss of taste and smell. Above all, 88% of patients in intensive care have neurological manifestations, cognitive disorders: they are disturbed, confused. ” A geriatrician from the Pompidou hospital: “If in most cases these symptoms disappear spontaneously after seven to ten days, we still do not know the degree of recovery of the elderly, sometimes already fragile.”

Another surprise, “For six weeks, we have seen acrosyndromes, pseudo-frostbite at the extremities of the limbs”, reports Professor Lescure. This is cause for concern enough for the National Union of Dermatologists and Venerologists to launch an alert on April 8 for skin manifestations linked to Covid-19 infection – acrosyndromes, sudden onset of persistent, sometimes painful redness and temporary hives lesions.

Who is at risk?

Since the publication on February 24 of a large study by the China Center for Disease Control and Prevention, the profile of severely ill patients has been clarified. Professor Pialoux: “What strikes me is that patients admitted to intensive care are often diabetic, overweight or even obese.” A finding shared by all the hospitals that receive Covid-19 patients, French and European. And this is a real surprise because the first Chinese ascents only documented “classic” risk factors, such as age and the presence of comorbidities (high blood pressure, cardiovascular problems, pulmonary insufficiency, severe diabetes, etc.)

For the past two weeks, research work has confirmed clinical observations. A study published in late March in the Journal of the American Medical Association by Italian researchers, involving 955 deceased patients, established that 35% were diabetic. “We thought that only severe diabetics were concerned. Not at all, small diabetics are too. We have even discovered diabetes during hospitalization ”, points to Professor Lescure.

1er April, a new Chinese study published in The Lancet confirmed the role of the body mass index: out of 383 coronavirus patients admitted to a hospital in Shenzhen, 42% were overweight or obese. Researchers conclude: overweight people have an 86% chance of developing a severe form of Covid-19. Those who suffer from obesity have “Showed a 2 to 42 times higher probability of developing severe pneumonia” than other patients. The danger is real even for young patients: “Obesity is often the only risk factor for patients under 50 years of age in intensive care in Bichat”, says Professor Lescure. What confirms Professor Lila Bouadma, resuscitator at Bichat Hospital : “We have patients, young people, who were in perfect health, with only one weight problem.” A phenomenon that has not yet been elucidated. “Maybe it’s due to the fat cells that let the virus pass more easily”, wonders Karine Lacombe. It is also possible that being overweight amplifies the inflammatory reactions induced by the presence of the coronavirus in the body.

Another characteristic of heavily affected patients, which was already reported in the first Chinese study, caught infectious disease specialists short: gender inequality. “The coronavirus infects men and women in the same proportions but 80% of our intensive care patients are men”, notes Professor Lescure. This difference in resistance between the two sexes is not elucidated. Assumptions flourish. Researchers are particularly interested in the role of an enzyme (ACE2 installed on the X chromosome), essential in the production of estrogen, known for its anti-inflammatory influence.

How is the infection going?

The pattern is often repeated identically. In one in five cases, Covid-19 infection requires hospitalization for respiratory distress. A majority of these severely affected patients then have severe pneumonia with bilateral involvement, according to the WHO. Respiratory support is not always enough to overcome the infection. About seven days after the first symptoms appear, some patients suddenly get worse, with an inflammatory over-reaction of the immune system, known as the “cytokine storm”. However, this runaway can be fatal: instead of defending the body against inflammation, cytokines destroy not only infected cells but also healthy tissue in the lungs, heart or kidneys. Assessment: 20% of severe forms of Covid-19 have heart damage linked to the immune reaction. Professor Lacombe: “Compared to the first few weeks, the change is spectacular. We are facing an immunological disease much more than viral as we might have thought. It’s new. ” Professor Pialoux completes: “Like the first Chinese death on French soil, 10% of intensive care patients die not from the coronavirus directly but from pulmonary complications and sometimes pulmonary embolism. Such vascular complications have never been seen with influenza or SARS. “

Professor Lescure summarizes: “Clinical observation has allowed us to identify three sides of the disease. The first is infectious, viral. But in a certain number of serious patients, the inflammatory aspect becomes preponderant after the runaway of the immune system. The last side is vascular: the disease causes microvascular damage, thrombosis, which is supposed to be linked to inflammation, without being certain. “

When are you immunized and for how long?

This is a key point, and of particular interest to the High Scientific Council, currently mobilized on possible scenarios of deconfinement. In this area, he must do with good news, very bad news and a lot of uncertainty.

The good news first. According to a study by German researchers on the replication of the virus in the upper respiratory tract published in Nature 1er April, patients begin to produce antibodies seven to fourteen days after the first symptoms appear, and their viral load slowly decreases. “We think these antibodies are neutralizing, and therefore protect against re-infection, says Professor Lescure. It is a clinical hypothesis, not scientific certainty. But apart from a few cases reported in China at the start of the epidemic, which may have been only false positives, no one has seen any cases of reinfection. “

Next is the big tile. According to the modellers of the High Council, the French are not more than 10 to 15% to have been in contact with the virus until now, including in areas with high incidence such as the Grand-Est or the Ile-de -France. And this projection is undoubtedly still optimistic: the test campaign launched in the cluster of Oise concluded with a collective immunity of hardly more than 7%… In any case, we are very far from the rate of 60% of protected persons, floor threshold to claim this “group immunity” which would ward off the risk of a second wave of Covid-19. “In terms of public health, this is very problematic, confirms Xavier Lescure. A brutal lifting of containment would inevitably revive the epidemic. “. But too late, the problem could get worse. Because if a healed individual is immune, it is not known for how long …


Eric Favereau

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Nathalie Raulin

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Cell transplant restores vision in blind mice

Madrid

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US researchers have discovered a technique that can reprogram skin cells into light-sensitive rod photoreceptors necessary for vision. Thanks to the transplantation of these laboratory photoreceptors in the eyes of blind mice, it has allowed them to perceive light. The work, funded by the US National Eye Institute., is published today in Nature, is a great step in the treatment of eye diseases such as age-related macular degeneration.

Until now, researchers have replaced dying photoreceptors in animal models by making skin stem cells or blood cells, programming those stem cells to become photoreceptors, That transplanted to the back of the eye.

But, in the new study, scientists show that it is possible to skip the intermediate step stem cells and directly reprogram the skin cells into photoreceptors for subsequent transplantation to the retina.

“This is the first study to show that direct chemical reprogramming can produce retinal-like cells, which gives us a new and faster strategy to develop therapies for age-related acular degeneration and other disorders of the retina caused by the loss of photoreceptors, “he says. Anand Swaroop, study investigator.

This is the first study to show that direct chemical reprogramming can produce retinal-like cells.

“The immediate benefit will be the ability to develop rapidly disease models so that we can study the mechanisms of this pathology. The new strategy will also help us design better cell replacement approaches, “he says.

Scientists have studied induced pluripotent stem cells (iPS) for the past decade. The IP cells They are grown in a laboratory from adult cells, rather than fetal tissue, and can be used to produce almost any type of cell or replacement tissue.

However, iPS cell reprogramming protocols can be delayed six months until the cells or tissues are ready for transplant. In contrast, the direct reprogramming described in this work resulted in skin cells becoming functional transplant-ready photoreceptors. in just 10 days. The researchers demonstrated their technique in mouse eyes, using skin cells derived from mice and humans.

«Our technique goes directly from the skin cells to the photoreceptor without the need for mother cells as a step intermediate», Explains the principal investigator of the study, Sai Chavala, president of CIRC Therapeutics.

Direct reprogramming involves bathing the skin cells in a five compound cocktail of small molecules that together chemically mediate the molecular pathways relevant to the fate of the rod photoreceptor cell. The result is bar photoreceptors that mimic native bars in appearance and function.

Within one month of transplantation, (43%) animals showed robust pupil constriction in low light compared to none of the untreated controls.

The researchers transplanted the cells into mice with retinal degeneration and then tested their pupillary reflexes, which is a measure of photoreceptor function after transplantation. In low light conditions, pupil constriction depends on the function of the rod photoreceptor. Within one month of transplantation, six of 14 (43%) animals showed robust pupil constriction in low light compared to none of the untreated controls.

Furthermore, mice treated with pupil constriction were significantly more likely to search and spend time in dark spaces compared to mice treated with no pupil response and untreated controls. The preference for dark spaces It is behavior that requires vision and reflects the natural tendency of the mouse to look for safe and dark places instead of light.

“Even mice with severely advanced retinal degeneration, with little chance of having remaining live photoreceptors, responded to the transplant. Such findings suggest that the observed improvements were due to laboratory-made photoreceptors and not to an auxiliary effect that supported the health of existing photoreceptors, “confirms the study’s first author, Biraj Mahato.

Three months after the transplant, immunofluorescence studies confirmed the survival of laboratory photoreceptorsas well as its synaptic connections to neurons in the internal retina.

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UChicago begins plasma testing of patients who beat COVID-19 – Telemundo Chicago

The University of Chicago Medicine started a clinical trial to study whether the blood plasma of people who have recovered from COVID-19 can be used to treat hospitalized patients in serious condition.

The trial will recruit plasma donors from existing UChicago Medicine patients and others in Chicago who tested positive and recovered from COVID-19. These plasma donations will be used to treat patients currently hospitalized at UChicago Medicine. The initial study will investigate only the safety and feasibility of procedures to identify donors, collect plasma donations, and administer transfusions. Further study of the effectiveness of such treatment will require additional trials.

“This trial is only the first step, but hopefully it will help us determine if plasma transfusions can be a treatment for critically ill patients with COVID-19,” he said. Asst. Prof. Maria Lucia Madariaga, a thoracic and lung transplant general surgeon at UChicago Medicine who is leading the clinical trial.

As the COVID-19 pandemic spreads, hospitals around the world have begun testing plasma as a potential treatment, including those in China, as well as in New York City and Houston.

“There has been a great barrier to widespread study in the United States because it requires extensive collaboration across disciplines,” said Madariaga. “At UChicago, we are very fortunate to have all of the equipment necessary to perform a convalescent plasma test under one roof: Division of Biological Sciences, Blood Bank, Department of Medicine, Institute of Transplants, and Department of Surgery.”

Plasma is the liquid in which blood cells are suspended. When someone is infected with a virus, the body’s immune system produces proteins called antibodies that can search for and neutralize the virus. Transfusion of plasma containing these antibodies into seriously ill patients could give your immune system additional resources to fight infection. After a patient recovers, the antibodies remain in their blood and can provide immunity; however, it is not yet known how long a patient is immune once they have recovered from COVID-19.

Donating plasma for testing is similar to donating blood. A single donation of plasma from one patient can be used for multiple recipients. Participants will donate a unit of blood that can be transfused to current UChicago patients in serious or critical condition for COVID-19. Once the researchers evaluate the safety and feasibility of this process, they can begin additional trials to study the effectiveness of plasma transfusions as a treatment.

The researchers will recruit adults in Chicago who tested positive and recovered from COVID-19 to donate blood and participate in the study. Those interested in participating and donating plasma can visit the convalescent plasma study website COVID-19, send an email to plasma@uchospitals.edu or call 773-702-5526.

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USA try a stem cell therapy for coronavirus

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The United States Food and Drug Administration (FDA) just approved the application for the use of CYNK-001 in adults with COVID-19 to start a phase I / II clinical trial that will include up to 86 patients. The biotechnology company Cellularity believes that CYNK-001 It is the first drug of this type of immunotherapy approved by the FDA to treat adults infected with coronavirus.

Although the treatment has not yet been used in any patient with symptoms of Covid-19, “it represents a significant step toward possible treatment for patients infected with the COVID-19 virus,” said Robert Hariri, Founder, President and CEO of Celularity. “With our clinical study we will gain an understanding of the impact CYNK-001 can have on patients recently diagnosed with COVID-19. We hope to contribute to flatten the curve of COVID-19, expanding on the promising initial results we have seen in clinical trials in some cancers in patients with coronavirus ».

We hope to help flatten the COVID-19 curve, expanding on the promising initial results we have seen in clinical trials on some cancers in patients with coronavirus.

CYNK-001 is the only cell therapy natural allogeneic killers (NK) cryopreserved It is being developed from placental hematopoietic stem cells and is being investigated as a potential treatment option for various hematologic cancers and solid tumors.

The cells NK they are a unique class of immune cells, innately capable of attacking cancer cells and interacting with adaptive immunity. The cellss CYNK-001 derived from the placenta they are intrinsically safe and versatile and are currently being investigated as a treatment for myeloid leukemiaacute, multiple myeloma and glioblastoma multiforme.

“Studies have established that there is a robust activation of NK cells during viral infection, regardless of the class of virus “, explains the scientific director of Cellularity, Xiaokui Zhang. CYNK-001 demonstrates a variety of biological activities expected from NK cells. These functions suggest that CYNK-001 could provide a benefit to COVID-19 patients in terms of limit replication SARS-CoV-2 and the disease progression by removing infected cells. “

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“ethical cells” are being set up all over France

Here again, we had to act quickly. No sooner had the proposal, Friday March 13, been formulated by the National Consultative Ethics Committee (CCNE) to set up “ethical cells” than their implementation was launched, under the responsibility of “regional ethical spaces “, Which have existed for several years. At the start of the week, Professor Grégoire Moutel set up, for Normandy, a team of 9 people, constituting one of the first of its kind in France.

→ LIVE. Coronavirus: France enters its 3rd day of total containment

“We have four functions, he explains: help professionals in difficulty of decision; ensure the dissemination of recommendations; mediate between caregivers and families; and after the crisis, learn from everything we are going through.

The situation of older people

Questions already go back to this team, made up in particular of several doctors but also of a philosopher, a sociologist and a representative of a patient association. During these first hours, they mainly focus on the situation of the elderly.

“At the beginning of the week, some doctors from Samu asked us if it was possible that they would no longer be referred to certain patients coming from nursing homes, when they are in a serious geriatric state Explains Grégoire Moutel. Tuesday March 17 and Wednesday March 18, it was the staff of these establishments themselves who contacted the ethics unit in Normandy, concerning three people. All very old, in a very degraded physical state and affected by the coronavirus.

→ READ. Coronavirus: the difficult priority rules in hospital

“The staff at these retirement homes do not know how to cope. Families also obviously find it difficult to accept that they are considering not transferring their loved one to the hospital and to consider the end of their lives. ”, specifies Grégoire Moutel. Faced with this, he tries, with his team, to keep a crest line: listen, advise, remind existing managers, without ever making a decision in place of the others.

“In the field, many ignore, for example, the framework of the Claeys-Leonetti law on end of life, which prohibits relentless therapy, explains the Norman practitioner again. I also encourage establishments to see if their residents have established advance directives where their wishes are set for their end of life..

Vital emergencies and disabilities

These cells, in Normandy and elsewhere, are also preparing for a saturation of resuscitation services. And the choices that doctors will be forced to make between several patients due to lack of resources. It is already starting in some resuscitation services in eastern France: in Alsace, the ethics unit should also be set up by Friday March 20.

In the Bouches-du-Rhône, it has already emerged. “ We agreed that for difficult decisions, we would never talk about triage, explains, in Marseille, the philosopher Pierre Le Coz. It’s a military term that is too violent for civilian populations. Our objective, during these difficult times, will be to provide support, including psychological, to caregivers. We know that every decision will necessarily involve a little arbitrariness but between an absolute arbitrariness and a relative arbitrariness, it is better a relative arbitrariness

→ EXPLANATION. Faced with the coronavirus, the State establishes “the state of health emergency”

The Marseille ethics unit plans to meet at least once a week, every Tuesday. “For later, we will see,” continues the philosopher. The requests will probably multiply, and we will have to adapt our responses to each. We cannot just say that we must respect the dignity of the person. Everyone is different. Thus, we may be overwhelmed with requests, but we must take this risk. “

Four working groups in Paris

But the questions that the “regional ethical spaces”, particularly mobilized for this crisis, are trying to answer, sometimes also go beyond the dilemmas of caregivers confronted with a vital emergency. This is the case in Paris, where the Ile-de-France ethical area has launched four working groups linked to the coronavirus, including one on disability and old age.

“We identify the questions and share our thoughts widely with the 12,000 people in our network”, explains Sébastien Claeys, in charge of this working group. ” We have specific questions that arise in people with disabilities, such as the role of their caregiver. Should these auxiliaries, for example, only take care of one person to limit contamination, but at the risk of neglecting the others? In an institution, how to manage a disabled person who is very dependent and infected? How do you deal with the loneliness of older people? “, Details this researcher.

He adds : “Basically, we are at the moment of ethical reflection in action, whether these are vital questions or not. Yes, we are in an emergency. But in an emergency, we must act. And for that, we must never give up asking questions. “

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A text to guide doctors

To inform their decisions, doctors can rely on a text, delivered Tuesday 17 to the Directorate General of Health and sent to hospitals. Entitled “Prioritizing Access to Critical Care in the Context of a Pandemic,” it sets out principles for “screening” patients requiring resuscitation care.

This document is based in particular on a “clinical frailty score”. Familiar with hospital staff, it allows patients to be classified according to their state of health, from the “very fit” person to the “terminally ill” person.

If, in a context of crisis, age can constitute a criterion – a very young person could be considered as a priority compared to a very old person -, it is not decisive on its own.

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New step in creating blood stem cells in the laboratory

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Scientists from the Stem Cell and Cancer Research Group of the Hospital del Mar Institute for Medical Research(IMIM), in Barcelona, ​​have led a study that has managed to determine the role of two molecules, Dll4 and Notch, and the importance of its interaction in the generation of blood stem cells.

The finding is a very important step in research to find a viable method that allows generating this type of cell in the laboratory.

The study, in which researchers from European universities and Tel Aviv have participated, has been published in the journal The EMBO Journal.

Until now, a cell with blood stem cell characteristics has not been obtained in the laboratory, say the authors.

At the present time, “they can be erythrocytes, platelets, many blood products in the laboratory, but it has never been possible to make a cell that has the characteristics of a blood stem cell “, explains lAnna Bigas, group coordinator and lead author of the study.

Being able to find a method to create this type of cell would allow patients with diseases such as leukemia or certain genetic pathologies what affect the blood and who do not have a compatible donor, can receive a hematopoietic stem cell transplant, which in many cases is the only possible treatment.

The work has focused on the role of two molecules, Notch and Dll4, and their relationship in the process by which the body naturally generates stem cells. Specifically, they are formed during the embryonic process and are no longer generated once this process is finished. These cells come from the endothelium, the tissue that lines the inside of all blood vessels.

The group has analyzed in mouse embryos the process by which endothelial cells become blood stem cells. And they have been able to verify that the interaction between the two molecules that the different cells express on their surface is vital.

They have analyzed in mouse embryos the process by which endothelial cells become blood stem cells

“If this cellular interaction that occurs thanks to Notch and Dll4 proteins is blocked, cells that were not yet stem cells transform into this type of cell,” explains Bigas. That is to say, “Interfering with the interaction between these two molecules enhances the fact that they become stem cells hematopoietic ».

Until now, the role of Notch was known, but not that of Dll4. There was also no evidence of the importance of the relationship between the two molecules.

The study was carried out thanks to antibodies designed to block the Dll4 protein. Cells from mouse embryos treated with these antibodies were introduced into adult specimens to see if they maintained their properties as blood stem cells. Successfully.

Now, the team will continue investigating this route, but stresses that it is not the only one involved in the process and that it will have to be validated if it is a useful tool for stem cell generation of blood in the laboratory from, for example, embryonic cells.

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