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New study shows natural immunity to COVID has enduring strength

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It’s a matter of quality, not quantity. That’s the gist of a new Israeli study that shows that unvaccinated people with a prior SARS-CoV-2 infection create antibodies that are more effective in the long run compared with others who were vaccinated but never infected.

“While the quantity of antibodies decreases with time in both COVID-19 recovered patients and vaccinated individuals, the quality of antibody performance increases following infection but not after vaccination,” lead author Carmit Cohen, PhD, said in an interview.

This difference could explain why previously infected patients appear to be better protected against a new infection than those who have only been vaccinated, according to a news release attached to the research.

One key caveat: This research does not include people from the later part of the pandemic.

This means there is a catch in terms of timing, William Schaffner, MD, Vanderbilt University School of Medicine, Nashville, Tenn., said when asked to comment on the study: “The study involved only the early COVID strains – it has no information on either the Delta or Omicron variants. Thus, the results primarily are of scientific or historical interest but are not immediately relevant to the current situation.”

The findings come from an early release of a study to be presented at the European Congress of Clinical Microbiology & Infectious Diseases in April.

An unexpected finding of the study showed that obese people had better protection – a higher and more sustained immune response – compared with overweight and normal-weight individuals.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” Dr. Schaffner said. “Obesity does predispose to more severe disease.”
 

A focus on earlier strains

Dr. Cohen – a senior research assistant in infectious disease prevention at the Sheba Medical Center in Ramat Gan, Israel – and her colleagues recruited participants between March 25, 2020 and Nov. 25, 2020 and completed analysis in April 2021. This means they assessed people with a history of infection from the original, the Alpha, and some Beta strains of SARS-CoV-2.

Dr. Cohen indicated that the next phase of their research will examine innate and acquired immune responses to the more recent Delta and Omicron variants.

The investigators analyzed the antibody-induced immune response up to 1 year in 130 COVID-19 recovered but unvaccinated individuals versus up to 8 months among 402 others matched by age and body mass index (BMI) and without previous infection who received two doses of the Pfizer vaccine.

The numbers of antibodies a month after vaccination were higher than those in the COVID-19 recovered patients. However, these numbers also declined more steeply in the vaccinated group, they note.

To assess the antibody performance, the investigators used the avidity index. This assay measures antibody function based on the strength of the interactions between the antibody and the viral antigen.

They found that the avidity index was higher in vaccinated individuals than in recovered patients initially but changes over time. At up to 6 months, the index did not significantly change in vaccinated individuals, whereas it gradually increased in recovered patients. This increase would potentially protect them from reinfection, the authors note.

These findings stand in stark contrast to an Oct. 29, 2021, Centers for Disease Control and Prevention study that found that COVID-19 vaccines provided five times the protection of natural immunity.

Those results, published in the organization’s Morbidity and Mortality Weekly Report, suggest that vaccination helps people mount a higher, stronger, and more consistent level of immunity against COVID-19 hospitalization than infection alone for at least 6 months.
 

 

 

Protection linked to obesity

Another finding that ran against the scientific grain was the data about obesity.

There was a higher and more persistent antibody performance among people with a BMI of 30 kg/m2.

This could relate to greater disease severity and/or a more pronounced initial response to infection among the obese group.

“Our hypothesis is that patients with obesity begin with a more pronounced response – reflected also by the disease manifestation – and the trend of decline is similar, therefore the kinetics of immune response remain higher throughout the study,” Dr. Cohen said.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” said Dr. Schaffner, who is also the current medical director of the National Foundation for Infectious Diseases. “Obesity does predispose to more severe disease.”
 

Before the boosters

Along with using participants from only the earlier part of the pandemic, another limitation of the study was that the vaccinated group had only two doses of vaccine; boosters were not given during the time of the study, Dr. Schaffner said.

“Again, not the current situation.”

“That said, the strength and duration of natural immunity provided by the early variants was solid for up to a year, confirming previous reports,” he said.

A version of this article first appeared on Medscape.com.

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It’s a matter of quality, not quantity. That’s the gist of a new Israeli study that shows that unvaccinated people with a prior SARS-CoV-2 infection create antibodies that are more effective in the long run compared with others who were vaccinated but never infected.

“While the quantity of antibodies decreases with time in both COVID-19 recovered patients and vaccinated individuals, the quality of antibody performance increases following infection but not after vaccination,” lead author Carmit Cohen, PhD, said in an interview.

This difference could explain why previously infected patients appear to be better protected against a new infection than those who have only been vaccinated, according to a news release attached to the research.

One key caveat: This research does not include people from the later part of the pandemic.

This means there is a catch in terms of timing, William Schaffner, MD, Vanderbilt University School of Medicine, Nashville, Tenn., said when asked to comment on the study: “The study involved only the early COVID strains – it has no information on either the Delta or Omicron variants. Thus, the results primarily are of scientific or historical interest but are not immediately relevant to the current situation.”

The findings come from an early release of a study to be presented at the European Congress of Clinical Microbiology & Infectious Diseases in April.

An unexpected finding of the study showed that obese people had better protection – a higher and more sustained immune response – compared with overweight and normal-weight individuals.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” Dr. Schaffner said. “Obesity does predispose to more severe disease.”
 

A focus on earlier strains

Dr. Cohen – a senior research assistant in infectious disease prevention at the Sheba Medical Center in Ramat Gan, Israel – and her colleagues recruited participants between March 25, 2020 and Nov. 25, 2020 and completed analysis in April 2021. This means they assessed people with a history of infection from the original, the Alpha, and some Beta strains of SARS-CoV-2.

Dr. Cohen indicated that the next phase of their research will examine innate and acquired immune responses to the more recent Delta and Omicron variants.

The investigators analyzed the antibody-induced immune response up to 1 year in 130 COVID-19 recovered but unvaccinated individuals versus up to 8 months among 402 others matched by age and body mass index (BMI) and without previous infection who received two doses of the Pfizer vaccine.

The numbers of antibodies a month after vaccination were higher than those in the COVID-19 recovered patients. However, these numbers also declined more steeply in the vaccinated group, they note.

To assess the antibody performance, the investigators used the avidity index. This assay measures antibody function based on the strength of the interactions between the antibody and the viral antigen.

They found that the avidity index was higher in vaccinated individuals than in recovered patients initially but changes over time. At up to 6 months, the index did not significantly change in vaccinated individuals, whereas it gradually increased in recovered patients. This increase would potentially protect them from reinfection, the authors note.

These findings stand in stark contrast to an Oct. 29, 2021, Centers for Disease Control and Prevention study that found that COVID-19 vaccines provided five times the protection of natural immunity.

Those results, published in the organization’s Morbidity and Mortality Weekly Report, suggest that vaccination helps people mount a higher, stronger, and more consistent level of immunity against COVID-19 hospitalization than infection alone for at least 6 months.
 

 

 

Protection linked to obesity

Another finding that ran against the scientific grain was the data about obesity.

There was a higher and more persistent antibody performance among people with a BMI of 30 kg/m2.

This could relate to greater disease severity and/or a more pronounced initial response to infection among the obese group.

“Our hypothesis is that patients with obesity begin with a more pronounced response – reflected also by the disease manifestation – and the trend of decline is similar, therefore the kinetics of immune response remain higher throughout the study,” Dr. Cohen said.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” said Dr. Schaffner, who is also the current medical director of the National Foundation for Infectious Diseases. “Obesity does predispose to more severe disease.”
 

Before the boosters

Along with using participants from only the earlier part of the pandemic, another limitation of the study was that the vaccinated group had only two doses of vaccine; boosters were not given during the time of the study, Dr. Schaffner said.

“Again, not the current situation.”

“That said, the strength and duration of natural immunity provided by the early variants was solid for up to a year, confirming previous reports,” he said.

A version of this article first appeared on Medscape.com.

It’s a matter of quality, not quantity. That’s the gist of a new Israeli study that shows that unvaccinated people with a prior SARS-CoV-2 infection create antibodies that are more effective in the long run compared with others who were vaccinated but never infected.

“While the quantity of antibodies decreases with time in both COVID-19 recovered patients and vaccinated individuals, the quality of antibody performance increases following infection but not after vaccination,” lead author Carmit Cohen, PhD, said in an interview.

This difference could explain why previously infected patients appear to be better protected against a new infection than those who have only been vaccinated, according to a news release attached to the research.

One key caveat: This research does not include people from the later part of the pandemic.

This means there is a catch in terms of timing, William Schaffner, MD, Vanderbilt University School of Medicine, Nashville, Tenn., said when asked to comment on the study: “The study involved only the early COVID strains – it has no information on either the Delta or Omicron variants. Thus, the results primarily are of scientific or historical interest but are not immediately relevant to the current situation.”

The findings come from an early release of a study to be presented at the European Congress of Clinical Microbiology & Infectious Diseases in April.

An unexpected finding of the study showed that obese people had better protection – a higher and more sustained immune response – compared with overweight and normal-weight individuals.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” Dr. Schaffner said. “Obesity does predispose to more severe disease.”
 

A focus on earlier strains

Dr. Cohen – a senior research assistant in infectious disease prevention at the Sheba Medical Center in Ramat Gan, Israel – and her colleagues recruited participants between March 25, 2020 and Nov. 25, 2020 and completed analysis in April 2021. This means they assessed people with a history of infection from the original, the Alpha, and some Beta strains of SARS-CoV-2.

Dr. Cohen indicated that the next phase of their research will examine innate and acquired immune responses to the more recent Delta and Omicron variants.

The investigators analyzed the antibody-induced immune response up to 1 year in 130 COVID-19 recovered but unvaccinated individuals versus up to 8 months among 402 others matched by age and body mass index (BMI) and without previous infection who received two doses of the Pfizer vaccine.

The numbers of antibodies a month after vaccination were higher than those in the COVID-19 recovered patients. However, these numbers also declined more steeply in the vaccinated group, they note.

To assess the antibody performance, the investigators used the avidity index. This assay measures antibody function based on the strength of the interactions between the antibody and the viral antigen.

They found that the avidity index was higher in vaccinated individuals than in recovered patients initially but changes over time. At up to 6 months, the index did not significantly change in vaccinated individuals, whereas it gradually increased in recovered patients. This increase would potentially protect them from reinfection, the authors note.

These findings stand in stark contrast to an Oct. 29, 2021, Centers for Disease Control and Prevention study that found that COVID-19 vaccines provided five times the protection of natural immunity.

Those results, published in the organization’s Morbidity and Mortality Weekly Report, suggest that vaccination helps people mount a higher, stronger, and more consistent level of immunity against COVID-19 hospitalization than infection alone for at least 6 months.
 

 

 

Protection linked to obesity

Another finding that ran against the scientific grain was the data about obesity.

There was a higher and more persistent antibody performance among people with a BMI of 30 kg/m2.

This could relate to greater disease severity and/or a more pronounced initial response to infection among the obese group.

“Our hypothesis is that patients with obesity begin with a more pronounced response – reflected also by the disease manifestation – and the trend of decline is similar, therefore the kinetics of immune response remain higher throughout the study,” Dr. Cohen said.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” said Dr. Schaffner, who is also the current medical director of the National Foundation for Infectious Diseases. “Obesity does predispose to more severe disease.”
 

Before the boosters

Along with using participants from only the earlier part of the pandemic, another limitation of the study was that the vaccinated group had only two doses of vaccine; boosters were not given during the time of the study, Dr. Schaffner said.

“Again, not the current situation.”

“That said, the strength and duration of natural immunity provided by the early variants was solid for up to a year, confirming previous reports,” he said.

A version of this article first appeared on Medscape.com.

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To a perfect day

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Wed, 02/16/2022 - 12:27

Motionless, every Olympic skater starts off perfectly. Once the music starts, it’s up to them whether they will continue on perfectly or not. In this way, you’re just like an Olympic skater. Each day, a skating program. The music starts the moment your foot touches the floor in the morning. It’s up to you if the rest of the day will continue on flawlessly or not. To this point, I’ve yet to have a perfect day.

If I’m honest, my “perfect day” streak typically ends once I’ve made coffee. By then, I’ll have spilled a few grains of grounds or clinked mugs together when taking one from the cupboard. (D’oh!) Hardly ever can I make it to backing out of the driveway, let alone through a patient encounter. I’ve had a few procedures that when complete I’ve thought, “well, that looks great.” I can remember encounters that went brilliantly despite a high technical difficulty. I’ve also tagged a 7-iron shot 160 downwind yards to within inches of the cup. But I’ve hardly ever done anything in my life perfectly.

Dr. Jeffrey Benabio

What does it mean to be perfect? Well, there have been 23 perfect baseball games. In 1972, the Miami Dolphins had the only perfect NFL season, 14-0 (although my 2007 Patriots went 18-0 before losing to the – ugh – Giants). Every year, several hundred students score a perfect 1600 on the SAT. In an underground vault somewhere in France is a perfect sphere, a perfectly spherical 1-kg mass of pure silicon. There are at least 51 perfect numbers. And model Bella Hadid’s exactly 1.62-ratioed face is said to be perfectly beautiful. But yet, U.S. skater Nathan Chen’s seemingly flawless 113.97-point short program in Beijing, still imperfect.

Attempting a perfect day or perfect surgery or a perfect pour over coffee is a fun game, but perfectionism has an insidious side. Having perfectionistic concerns significantly increases the risk for burnout, depression, and eating disorders. Some of us feel this way every day: We must do it exactly right, every time. Even an insignificant imperfection or error feels like failure. A 3.90 GPA is a fail. 515 on the MCAT, not nearly good enough. For them, the burden of perfection is crushing. It is hard for some to recognize that even if your performance could not be improved, the outcome can still be flawed. A chip in the ice, a patient showing up late, an interviewer with an agenda, a missed referee call can all flub up an otherwise flawless day. It isn’t necessary to abandon hope, all ye who live in the real world. Although achieving perfection is usually impossible, reward comes from the pursuit of perfection, not from holding it. It is called perfectionistic striving and in contrast to perfectionistic concerns, it is associated with resilience and positive mood. To do so you must combine giving your all with acceptance of whatever the outcome.



Keith Jarrett is one of the greatest jazz pianists of all time. He is a true perfectionist, precise in his standards and exacting in expectations. In 1975 in Cologne, Germany, he agreed to play at the behest of a teenage girl who arranged to have him perform at the opera house. Except, there was a miscommunication and only a small, broken rehearsal piano was available. As the story goes, she approached him as he waited to be taken back to his hotel, the concert was canceled and she somehow convinced him to play on the nearly unplayable instrument. The result is the Köln Concert, one of the greatest jazz performances in history. It was perfectly imperfect.

Yes, even the 1-kg sphere has femtogram quantities of other elements mixed in – the universal standard for perfect is itself, imperfect. It doesn’t matter. It’s the pursuit of such that makes life worthwhile. There’s always tomorrow. Have your coffee grinders ready.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

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Motionless, every Olympic skater starts off perfectly. Once the music starts, it’s up to them whether they will continue on perfectly or not. In this way, you’re just like an Olympic skater. Each day, a skating program. The music starts the moment your foot touches the floor in the morning. It’s up to you if the rest of the day will continue on flawlessly or not. To this point, I’ve yet to have a perfect day.

If I’m honest, my “perfect day” streak typically ends once I’ve made coffee. By then, I’ll have spilled a few grains of grounds or clinked mugs together when taking one from the cupboard. (D’oh!) Hardly ever can I make it to backing out of the driveway, let alone through a patient encounter. I’ve had a few procedures that when complete I’ve thought, “well, that looks great.” I can remember encounters that went brilliantly despite a high technical difficulty. I’ve also tagged a 7-iron shot 160 downwind yards to within inches of the cup. But I’ve hardly ever done anything in my life perfectly.

Dr. Jeffrey Benabio

What does it mean to be perfect? Well, there have been 23 perfect baseball games. In 1972, the Miami Dolphins had the only perfect NFL season, 14-0 (although my 2007 Patriots went 18-0 before losing to the – ugh – Giants). Every year, several hundred students score a perfect 1600 on the SAT. In an underground vault somewhere in France is a perfect sphere, a perfectly spherical 1-kg mass of pure silicon. There are at least 51 perfect numbers. And model Bella Hadid’s exactly 1.62-ratioed face is said to be perfectly beautiful. But yet, U.S. skater Nathan Chen’s seemingly flawless 113.97-point short program in Beijing, still imperfect.

Attempting a perfect day or perfect surgery or a perfect pour over coffee is a fun game, but perfectionism has an insidious side. Having perfectionistic concerns significantly increases the risk for burnout, depression, and eating disorders. Some of us feel this way every day: We must do it exactly right, every time. Even an insignificant imperfection or error feels like failure. A 3.90 GPA is a fail. 515 on the MCAT, not nearly good enough. For them, the burden of perfection is crushing. It is hard for some to recognize that even if your performance could not be improved, the outcome can still be flawed. A chip in the ice, a patient showing up late, an interviewer with an agenda, a missed referee call can all flub up an otherwise flawless day. It isn’t necessary to abandon hope, all ye who live in the real world. Although achieving perfection is usually impossible, reward comes from the pursuit of perfection, not from holding it. It is called perfectionistic striving and in contrast to perfectionistic concerns, it is associated with resilience and positive mood. To do so you must combine giving your all with acceptance of whatever the outcome.



Keith Jarrett is one of the greatest jazz pianists of all time. He is a true perfectionist, precise in his standards and exacting in expectations. In 1975 in Cologne, Germany, he agreed to play at the behest of a teenage girl who arranged to have him perform at the opera house. Except, there was a miscommunication and only a small, broken rehearsal piano was available. As the story goes, she approached him as he waited to be taken back to his hotel, the concert was canceled and she somehow convinced him to play on the nearly unplayable instrument. The result is the Köln Concert, one of the greatest jazz performances in history. It was perfectly imperfect.

Yes, even the 1-kg sphere has femtogram quantities of other elements mixed in – the universal standard for perfect is itself, imperfect. It doesn’t matter. It’s the pursuit of such that makes life worthwhile. There’s always tomorrow. Have your coffee grinders ready.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

Motionless, every Olympic skater starts off perfectly. Once the music starts, it’s up to them whether they will continue on perfectly or not. In this way, you’re just like an Olympic skater. Each day, a skating program. The music starts the moment your foot touches the floor in the morning. It’s up to you if the rest of the day will continue on flawlessly or not. To this point, I’ve yet to have a perfect day.

If I’m honest, my “perfect day” streak typically ends once I’ve made coffee. By then, I’ll have spilled a few grains of grounds or clinked mugs together when taking one from the cupboard. (D’oh!) Hardly ever can I make it to backing out of the driveway, let alone through a patient encounter. I’ve had a few procedures that when complete I’ve thought, “well, that looks great.” I can remember encounters that went brilliantly despite a high technical difficulty. I’ve also tagged a 7-iron shot 160 downwind yards to within inches of the cup. But I’ve hardly ever done anything in my life perfectly.

Dr. Jeffrey Benabio

What does it mean to be perfect? Well, there have been 23 perfect baseball games. In 1972, the Miami Dolphins had the only perfect NFL season, 14-0 (although my 2007 Patriots went 18-0 before losing to the – ugh – Giants). Every year, several hundred students score a perfect 1600 on the SAT. In an underground vault somewhere in France is a perfect sphere, a perfectly spherical 1-kg mass of pure silicon. There are at least 51 perfect numbers. And model Bella Hadid’s exactly 1.62-ratioed face is said to be perfectly beautiful. But yet, U.S. skater Nathan Chen’s seemingly flawless 113.97-point short program in Beijing, still imperfect.

Attempting a perfect day or perfect surgery or a perfect pour over coffee is a fun game, but perfectionism has an insidious side. Having perfectionistic concerns significantly increases the risk for burnout, depression, and eating disorders. Some of us feel this way every day: We must do it exactly right, every time. Even an insignificant imperfection or error feels like failure. A 3.90 GPA is a fail. 515 on the MCAT, not nearly good enough. For them, the burden of perfection is crushing. It is hard for some to recognize that even if your performance could not be improved, the outcome can still be flawed. A chip in the ice, a patient showing up late, an interviewer with an agenda, a missed referee call can all flub up an otherwise flawless day. It isn’t necessary to abandon hope, all ye who live in the real world. Although achieving perfection is usually impossible, reward comes from the pursuit of perfection, not from holding it. It is called perfectionistic striving and in contrast to perfectionistic concerns, it is associated with resilience and positive mood. To do so you must combine giving your all with acceptance of whatever the outcome.



Keith Jarrett is one of the greatest jazz pianists of all time. He is a true perfectionist, precise in his standards and exacting in expectations. In 1975 in Cologne, Germany, he agreed to play at the behest of a teenage girl who arranged to have him perform at the opera house. Except, there was a miscommunication and only a small, broken rehearsal piano was available. As the story goes, she approached him as he waited to be taken back to his hotel, the concert was canceled and she somehow convinced him to play on the nearly unplayable instrument. The result is the Köln Concert, one of the greatest jazz performances in history. It was perfectly imperfect.

Yes, even the 1-kg sphere has femtogram quantities of other elements mixed in – the universal standard for perfect is itself, imperfect. It doesn’t matter. It’s the pursuit of such that makes life worthwhile. There’s always tomorrow. Have your coffee grinders ready.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

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A third person living with HIV has been cured by transplant

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Fri, 02/18/2022 - 09:55

In a first, a middle-aged woman has been in remission from HIV for 14 months after being treated for leukemia with transplants of adult stem cells and umbilical cord blood. If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the Berlin Patient and the London Patient – to be cured through a transplant.

“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.

The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.

But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.

The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.

In this case, the physicians treating her used both.

“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.

Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.

One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.

This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.

“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”

The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.

“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.

“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.

And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”

Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.

But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.

For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.

“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”

Now the challenge is to move from a single case to making cure available to other people living with HIV.

The case also got cure researchers thinking.

Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.

Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”

For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.

“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”

Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.

“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”

When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.

“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”

The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

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In a first, a middle-aged woman has been in remission from HIV for 14 months after being treated for leukemia with transplants of adult stem cells and umbilical cord blood. If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the Berlin Patient and the London Patient – to be cured through a transplant.

“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.

The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.

But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.

The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.

In this case, the physicians treating her used both.

“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.

Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.

One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.

This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.

“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”

The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.

“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.

“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.

And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”

Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.

But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.

For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.

“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”

Now the challenge is to move from a single case to making cure available to other people living with HIV.

The case also got cure researchers thinking.

Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.

Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”

For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.

“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”

Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.

“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”

When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.

“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”

The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In a first, a middle-aged woman has been in remission from HIV for 14 months after being treated for leukemia with transplants of adult stem cells and umbilical cord blood. If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the Berlin Patient and the London Patient – to be cured through a transplant.

“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.

The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.

But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.

The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.

In this case, the physicians treating her used both.

“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.

Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.

One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.

This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.

“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”

The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.

“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.

“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.

And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”

Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.

But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.

For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.

“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”

Now the challenge is to move from a single case to making cure available to other people living with HIV.

The case also got cure researchers thinking.

Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.

Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”

For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.

“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”

Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.

“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”

When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.

“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”

The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

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Can first‐trimester HbA1c levels offer effective GDM diagnosis?

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Key clinical point: Although high first‐trimester glycated hemoglobin (HbA1c) levels are predictive of gestational diabetes mellitus (GDM), they cannot ensure effective GDM diagnosis owing to subpar sensitivity or specificity.

Main finding: An HbA1c cutoff value of 4.85% ruled out GDM with a diagnostic sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of 92.2%, 32.8%, 95.5%, and 21.2%, respectively, whereas HbA1c cutoff value of 5.45% for diagnosing GDM decreased sensitivity (54.8%) while increasing specificity (96.8%), with the NPV and PPV being 91.5% and 76.8%, respectively.

Study details: The data are derived from a single-center prospective study including 700 singleton pregnant women over 18 years of age who did not have type I or II diabetes mellitus.

Disclosures: The study was not funded by any source. The authors reported having no conflicts of interest.

Source: Valadan M et al. BMC Pregnancy Childbirth. 2022;22:71 (Jan 27). Doi: 10.1186/s12884-021-04330-2.

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Key clinical point: Although high first‐trimester glycated hemoglobin (HbA1c) levels are predictive of gestational diabetes mellitus (GDM), they cannot ensure effective GDM diagnosis owing to subpar sensitivity or specificity.

Main finding: An HbA1c cutoff value of 4.85% ruled out GDM with a diagnostic sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of 92.2%, 32.8%, 95.5%, and 21.2%, respectively, whereas HbA1c cutoff value of 5.45% for diagnosing GDM decreased sensitivity (54.8%) while increasing specificity (96.8%), with the NPV and PPV being 91.5% and 76.8%, respectively.

Study details: The data are derived from a single-center prospective study including 700 singleton pregnant women over 18 years of age who did not have type I or II diabetes mellitus.

Disclosures: The study was not funded by any source. The authors reported having no conflicts of interest.

Source: Valadan M et al. BMC Pregnancy Childbirth. 2022;22:71 (Jan 27). Doi: 10.1186/s12884-021-04330-2.

Key clinical point: Although high first‐trimester glycated hemoglobin (HbA1c) levels are predictive of gestational diabetes mellitus (GDM), they cannot ensure effective GDM diagnosis owing to subpar sensitivity or specificity.

Main finding: An HbA1c cutoff value of 4.85% ruled out GDM with a diagnostic sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of 92.2%, 32.8%, 95.5%, and 21.2%, respectively, whereas HbA1c cutoff value of 5.45% for diagnosing GDM decreased sensitivity (54.8%) while increasing specificity (96.8%), with the NPV and PPV being 91.5% and 76.8%, respectively.

Study details: The data are derived from a single-center prospective study including 700 singleton pregnant women over 18 years of age who did not have type I or II diabetes mellitus.

Disclosures: The study was not funded by any source. The authors reported having no conflicts of interest.

Source: Valadan M et al. BMC Pregnancy Childbirth. 2022;22:71 (Jan 27). Doi: 10.1186/s12884-021-04330-2.

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Copresence of amniotic fluid sludge and a short cervix affects preterm birth in women with cerclage

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Key clinical point: Presence of amniotic fluid sludge (AFS) in the midtrimester may serve as an additional ultrasound index for predicting preterm birth in women with a short cervical length (CL; 25 mm) who have undergone cervical cerclage.

Main finding: In patients who underwent cerclage, AFS and short CL were associated with preterm birth at <28 weeks and <36 weeks (all P < .05). In women with a short CL, the presence of AFS was significantly associated with short gestational age at delivery even after adjusting for possible confounders (adjusted hazard ratio 2.45; 95% CI 1.7-3.5).

Study details: This was a single-center retrospective cohort study involving 296 singleton pregnant women who underwent McDonald cerclage for cervical insufficiency, transvaginal ultrasound-diagnosed short CL, or cervical dilatation with amniotic sac bulging, followed by evaluation of the presence of AFS and CL at 14-24 weeks of gestation within 2 weeks after cerclage.

Disclosures: The authors reported no source of funding or conflict of interests concerning the study.

Source: Huang Y et al. J Ultrasound Med. 2022 (Feb 2). Doi: 10.1002/jum.15952.

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Key clinical point: Presence of amniotic fluid sludge (AFS) in the midtrimester may serve as an additional ultrasound index for predicting preterm birth in women with a short cervical length (CL; 25 mm) who have undergone cervical cerclage.

Main finding: In patients who underwent cerclage, AFS and short CL were associated with preterm birth at <28 weeks and <36 weeks (all P < .05). In women with a short CL, the presence of AFS was significantly associated with short gestational age at delivery even after adjusting for possible confounders (adjusted hazard ratio 2.45; 95% CI 1.7-3.5).

Study details: This was a single-center retrospective cohort study involving 296 singleton pregnant women who underwent McDonald cerclage for cervical insufficiency, transvaginal ultrasound-diagnosed short CL, or cervical dilatation with amniotic sac bulging, followed by evaluation of the presence of AFS and CL at 14-24 weeks of gestation within 2 weeks after cerclage.

Disclosures: The authors reported no source of funding or conflict of interests concerning the study.

Source: Huang Y et al. J Ultrasound Med. 2022 (Feb 2). Doi: 10.1002/jum.15952.

Key clinical point: Presence of amniotic fluid sludge (AFS) in the midtrimester may serve as an additional ultrasound index for predicting preterm birth in women with a short cervical length (CL; 25 mm) who have undergone cervical cerclage.

Main finding: In patients who underwent cerclage, AFS and short CL were associated with preterm birth at <28 weeks and <36 weeks (all P < .05). In women with a short CL, the presence of AFS was significantly associated with short gestational age at delivery even after adjusting for possible confounders (adjusted hazard ratio 2.45; 95% CI 1.7-3.5).

Study details: This was a single-center retrospective cohort study involving 296 singleton pregnant women who underwent McDonald cerclage for cervical insufficiency, transvaginal ultrasound-diagnosed short CL, or cervical dilatation with amniotic sac bulging, followed by evaluation of the presence of AFS and CL at 14-24 weeks of gestation within 2 weeks after cerclage.

Disclosures: The authors reported no source of funding or conflict of interests concerning the study.

Source: Huang Y et al. J Ultrasound Med. 2022 (Feb 2). Doi: 10.1002/jum.15952.

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Predictive value of NIPT-plus differs with maternal age

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Key clinical point: Expanded noninvasive prenatal testing (NIPT-plus) is better at predicting fetal chromosome abnormalities in pregnant women of advanced maternal age (AMA) than in those of young maternal age (YMA).

Main finding: The positive predictive value of NIPT-plus in AMA pregnancies vs. YMA pregnancies was 57.6% vs. 35.7% (P < .05) for sex chromosome aneuploidies (SCA) and 77.8% vs. 51.9% (P < .05) for chromosome aneuploidies, including trisomies 21, 18, and 13, and SCAs.

Study details: The data come from a retrospective cohort study including 448 pregnant women with screen-positive results by NIPT-plus for fetal chromosome abnormality in the second trimester, who underwent prenatal diagnosis, of which 27% were AMA pregnancies.

Disclosures: The study was funded by the National Nature Science Foundation of China. None of the authors reported having a conflicts of interests.

Source: Chen Y et al. Am J Med Genet A. 2022 (Feb 2). Doi: 10.1002/ajmg.a.62657.

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Key clinical point: Expanded noninvasive prenatal testing (NIPT-plus) is better at predicting fetal chromosome abnormalities in pregnant women of advanced maternal age (AMA) than in those of young maternal age (YMA).

Main finding: The positive predictive value of NIPT-plus in AMA pregnancies vs. YMA pregnancies was 57.6% vs. 35.7% (P < .05) for sex chromosome aneuploidies (SCA) and 77.8% vs. 51.9% (P < .05) for chromosome aneuploidies, including trisomies 21, 18, and 13, and SCAs.

Study details: The data come from a retrospective cohort study including 448 pregnant women with screen-positive results by NIPT-plus for fetal chromosome abnormality in the second trimester, who underwent prenatal diagnosis, of which 27% were AMA pregnancies.

Disclosures: The study was funded by the National Nature Science Foundation of China. None of the authors reported having a conflicts of interests.

Source: Chen Y et al. Am J Med Genet A. 2022 (Feb 2). Doi: 10.1002/ajmg.a.62657.

Key clinical point: Expanded noninvasive prenatal testing (NIPT-plus) is better at predicting fetal chromosome abnormalities in pregnant women of advanced maternal age (AMA) than in those of young maternal age (YMA).

Main finding: The positive predictive value of NIPT-plus in AMA pregnancies vs. YMA pregnancies was 57.6% vs. 35.7% (P < .05) for sex chromosome aneuploidies (SCA) and 77.8% vs. 51.9% (P < .05) for chromosome aneuploidies, including trisomies 21, 18, and 13, and SCAs.

Study details: The data come from a retrospective cohort study including 448 pregnant women with screen-positive results by NIPT-plus for fetal chromosome abnormality in the second trimester, who underwent prenatal diagnosis, of which 27% were AMA pregnancies.

Disclosures: The study was funded by the National Nature Science Foundation of China. None of the authors reported having a conflicts of interests.

Source: Chen Y et al. Am J Med Genet A. 2022 (Feb 2). Doi: 10.1002/ajmg.a.62657.

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Exome sequencing: A tool to explore the molecular defects of callosal anomalies

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Key clinical point: Diagnostic exome sequencing may enable the characterization of the molecular defects underlying unexplained callosal anomalies (CA) and potentially reduce the number of prenatally undiagnosed cases.

Main finding: A total of 17 pathogenic/likely pathogenic variants in 14 genes from 17 fetuses were identified, with the proportion of diagnostic genetic variants being 34%. Genetic variants were diagnosed in 29.4% and 43.8% of fetuses with isolated and nonisolated CA, respectively.

Study details: This single-center cohort study analyzed 50 fetuses with CA, with (n = 16) or without (n = 34) other structural abnormalities, but with normal karyotyping and chromosomal microarray analysis findings.

Disclosures: The study was sponsored by the National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, Project of Guangzhou Science and Technology, and Project of Guangdong Medical Science and Technology Research. No conflicts of interest were declared.

Source: Lei TY et al. Prenat Diagn. 2022 (Jan 28). Doi: 10.1002/pd.6107.

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Key clinical point: Diagnostic exome sequencing may enable the characterization of the molecular defects underlying unexplained callosal anomalies (CA) and potentially reduce the number of prenatally undiagnosed cases.

Main finding: A total of 17 pathogenic/likely pathogenic variants in 14 genes from 17 fetuses were identified, with the proportion of diagnostic genetic variants being 34%. Genetic variants were diagnosed in 29.4% and 43.8% of fetuses with isolated and nonisolated CA, respectively.

Study details: This single-center cohort study analyzed 50 fetuses with CA, with (n = 16) or without (n = 34) other structural abnormalities, but with normal karyotyping and chromosomal microarray analysis findings.

Disclosures: The study was sponsored by the National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, Project of Guangzhou Science and Technology, and Project of Guangdong Medical Science and Technology Research. No conflicts of interest were declared.

Source: Lei TY et al. Prenat Diagn. 2022 (Jan 28). Doi: 10.1002/pd.6107.

Key clinical point: Diagnostic exome sequencing may enable the characterization of the molecular defects underlying unexplained callosal anomalies (CA) and potentially reduce the number of prenatally undiagnosed cases.

Main finding: A total of 17 pathogenic/likely pathogenic variants in 14 genes from 17 fetuses were identified, with the proportion of diagnostic genetic variants being 34%. Genetic variants were diagnosed in 29.4% and 43.8% of fetuses with isolated and nonisolated CA, respectively.

Study details: This single-center cohort study analyzed 50 fetuses with CA, with (n = 16) or without (n = 34) other structural abnormalities, but with normal karyotyping and chromosomal microarray analysis findings.

Disclosures: The study was sponsored by the National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province, Project of Guangzhou Science and Technology, and Project of Guangdong Medical Science and Technology Research. No conflicts of interest were declared.

Source: Lei TY et al. Prenat Diagn. 2022 (Jan 28). Doi: 10.1002/pd.6107.

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Clinical Edge Journal Scan: Prenatal Testing March 2022
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Z-sign enables distinction between a right and double aortic arch during pregnancy

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Key clinical point: The Z-sign may serve as a strong marker for a double aortic arch (DAA) in surgically confirmed cases of vascular rings, even in those with atresia of the left arch, and thus facilitate the differentiation between a right aortic arch with left duct (RAA-LD) and DAA in the second trimester of pregnancy.

Main finding: The Z-sign could predict a DAA with a sensitivity of 100% (95% CI 80%-100%), specificity of 81% (95% CI 60%-92%), positive predictive value of 79% (95% CI 57%-91%), and negative predictive value of 100% (95% CI 82%-100%).

Study details: Findings are from a review of the echocardiographic features of 40 fetuses with either DAA or RAA-LD (those with the left duct connecting the pulmonary artery and descending aorta) confirmed during surgery, which displayed the commonest overlap in fetal appearances.

Disclosures: MPM Van Poppel received financial support from the Wellcome/EPSRC Centre for Medical Engineering. The other authors did not report any conflict of interests.

Source: Van Poppel MPM et al. Prenat Diagn. 2022 (Jan 20). Doi: 10.1002/pd.6104.

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Key clinical point: The Z-sign may serve as a strong marker for a double aortic arch (DAA) in surgically confirmed cases of vascular rings, even in those with atresia of the left arch, and thus facilitate the differentiation between a right aortic arch with left duct (RAA-LD) and DAA in the second trimester of pregnancy.

Main finding: The Z-sign could predict a DAA with a sensitivity of 100% (95% CI 80%-100%), specificity of 81% (95% CI 60%-92%), positive predictive value of 79% (95% CI 57%-91%), and negative predictive value of 100% (95% CI 82%-100%).

Study details: Findings are from a review of the echocardiographic features of 40 fetuses with either DAA or RAA-LD (those with the left duct connecting the pulmonary artery and descending aorta) confirmed during surgery, which displayed the commonest overlap in fetal appearances.

Disclosures: MPM Van Poppel received financial support from the Wellcome/EPSRC Centre for Medical Engineering. The other authors did not report any conflict of interests.

Source: Van Poppel MPM et al. Prenat Diagn. 2022 (Jan 20). Doi: 10.1002/pd.6104.

Key clinical point: The Z-sign may serve as a strong marker for a double aortic arch (DAA) in surgically confirmed cases of vascular rings, even in those with atresia of the left arch, and thus facilitate the differentiation between a right aortic arch with left duct (RAA-LD) and DAA in the second trimester of pregnancy.

Main finding: The Z-sign could predict a DAA with a sensitivity of 100% (95% CI 80%-100%), specificity of 81% (95% CI 60%-92%), positive predictive value of 79% (95% CI 57%-91%), and negative predictive value of 100% (95% CI 82%-100%).

Study details: Findings are from a review of the echocardiographic features of 40 fetuses with either DAA or RAA-LD (those with the left duct connecting the pulmonary artery and descending aorta) confirmed during surgery, which displayed the commonest overlap in fetal appearances.

Disclosures: MPM Van Poppel received financial support from the Wellcome/EPSRC Centre for Medical Engineering. The other authors did not report any conflict of interests.

Source: Van Poppel MPM et al. Prenat Diagn. 2022 (Jan 20). Doi: 10.1002/pd.6104.

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Clinical Edge Journal Scan: Prenatal Testing March 2022
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Risk for pathogenic chromosomal aberrations and CNVs in fetal CGIO

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Wed, 02/23/2022 - 14:00

Key clinical point: Fetuses with complicated congenital gastrointestinal obstruction (CGIO) vs. isolated CGIO are at a greater risk for chromosomal aberrations and pathogenic copy number variants (CNV).

Main finding: Fetuses with complicated CGIO showed a significantly higher detection rate of karyotype abnormalities (33.8% vs. 10.8%; P < .01) and overall detection rate of pathogenic CNVs (20% vs. 4.8%; P < .05) than those with isolated CGIO.

Study details: This retrospective study analyzed 240 fetuses prenatally diagnosed with CGIO who presented as either isolated (alone) or complicated (in combination with certain soft markers and structural abnormalities) and were referred for karyotyping or copy number variation sequencing.

Disclosures: No source of funding or conflict of interests were reported by the authors.

Source: Meng X, Jiang L. BMC Pregnancy Childbirth. 2022;22:50 (Jan 19). Doi: 10.1186/s12884-022-04401-y.

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Key clinical point: Fetuses with complicated congenital gastrointestinal obstruction (CGIO) vs. isolated CGIO are at a greater risk for chromosomal aberrations and pathogenic copy number variants (CNV).

Main finding: Fetuses with complicated CGIO showed a significantly higher detection rate of karyotype abnormalities (33.8% vs. 10.8%; P < .01) and overall detection rate of pathogenic CNVs (20% vs. 4.8%; P < .05) than those with isolated CGIO.

Study details: This retrospective study analyzed 240 fetuses prenatally diagnosed with CGIO who presented as either isolated (alone) or complicated (in combination with certain soft markers and structural abnormalities) and were referred for karyotyping or copy number variation sequencing.

Disclosures: No source of funding or conflict of interests were reported by the authors.

Source: Meng X, Jiang L. BMC Pregnancy Childbirth. 2022;22:50 (Jan 19). Doi: 10.1186/s12884-022-04401-y.

Key clinical point: Fetuses with complicated congenital gastrointestinal obstruction (CGIO) vs. isolated CGIO are at a greater risk for chromosomal aberrations and pathogenic copy number variants (CNV).

Main finding: Fetuses with complicated CGIO showed a significantly higher detection rate of karyotype abnormalities (33.8% vs. 10.8%; P < .01) and overall detection rate of pathogenic CNVs (20% vs. 4.8%; P < .05) than those with isolated CGIO.

Study details: This retrospective study analyzed 240 fetuses prenatally diagnosed with CGIO who presented as either isolated (alone) or complicated (in combination with certain soft markers and structural abnormalities) and were referred for karyotyping or copy number variation sequencing.

Disclosures: No source of funding or conflict of interests were reported by the authors.

Source: Meng X, Jiang L. BMC Pregnancy Childbirth. 2022;22:50 (Jan 19). Doi: 10.1186/s12884-022-04401-y.

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Clinical Edge Journal Scan: Prenatal Testing March 2022
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An ultrasound strategy for improving the prenatal detection of placenta accreta spectrum

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Key clinical point: Ultrasound evaluation performed following a standardized protocol is highly effective at detecting placenta accreta spectrum (PAS) in pregnant women with persistent placenta previa under real-world conditions.

Main finding: Of 126 patients with placenta previa, PAS was detected in 11 patients, of which 10 were diagnosed prenatally by ultrasound, exhibiting a sensitivity of 90.9%, specificity of 98.3%, positive predictive value of 83.3%, and negative predictive value of 99.1%.

Study details: This was a retrospective real-world cohort study involving 126 pregnant women with persistent placenta previa who underwent standardized transabdominal and transvaginal ultrasound to assess hypoechoic retroplacental zone loss or myometrial thinning <1 mm, lacunar images (flow >15 cm/second), thick and bulging placenta, uterine-bladder serous interface thinning/interruption, and placental/uterovesical hypervascularity; the presence of at least 1 was considered high-risk for PAS.

Disclosures: The authors disclosed receiving no financial support for the study and having no conflict of interests.

Source: Juan-Clar M et al. Fetal Diagn Ther. 2022 (Jan 11). Doi: 10.1159/000521738.

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Key clinical point: Ultrasound evaluation performed following a standardized protocol is highly effective at detecting placenta accreta spectrum (PAS) in pregnant women with persistent placenta previa under real-world conditions.

Main finding: Of 126 patients with placenta previa, PAS was detected in 11 patients, of which 10 were diagnosed prenatally by ultrasound, exhibiting a sensitivity of 90.9%, specificity of 98.3%, positive predictive value of 83.3%, and negative predictive value of 99.1%.

Study details: This was a retrospective real-world cohort study involving 126 pregnant women with persistent placenta previa who underwent standardized transabdominal and transvaginal ultrasound to assess hypoechoic retroplacental zone loss or myometrial thinning <1 mm, lacunar images (flow >15 cm/second), thick and bulging placenta, uterine-bladder serous interface thinning/interruption, and placental/uterovesical hypervascularity; the presence of at least 1 was considered high-risk for PAS.

Disclosures: The authors disclosed receiving no financial support for the study and having no conflict of interests.

Source: Juan-Clar M et al. Fetal Diagn Ther. 2022 (Jan 11). Doi: 10.1159/000521738.

Key clinical point: Ultrasound evaluation performed following a standardized protocol is highly effective at detecting placenta accreta spectrum (PAS) in pregnant women with persistent placenta previa under real-world conditions.

Main finding: Of 126 patients with placenta previa, PAS was detected in 11 patients, of which 10 were diagnosed prenatally by ultrasound, exhibiting a sensitivity of 90.9%, specificity of 98.3%, positive predictive value of 83.3%, and negative predictive value of 99.1%.

Study details: This was a retrospective real-world cohort study involving 126 pregnant women with persistent placenta previa who underwent standardized transabdominal and transvaginal ultrasound to assess hypoechoic retroplacental zone loss or myometrial thinning <1 mm, lacunar images (flow >15 cm/second), thick and bulging placenta, uterine-bladder serous interface thinning/interruption, and placental/uterovesical hypervascularity; the presence of at least 1 was considered high-risk for PAS.

Disclosures: The authors disclosed receiving no financial support for the study and having no conflict of interests.

Source: Juan-Clar M et al. Fetal Diagn Ther. 2022 (Jan 11). Doi: 10.1159/000521738.

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Clinical Edge Journal Scan: Prenatal Testing March 2022
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