CHICAGO - Posterior-stabilized (PS) bearings used in total knee arthroplasty (TKA) may increase the risk of revision compared with bearings of other design, new data suggest.

That possibility has previously been reported in studies outside the United States, and now an analysis of more than 300,000 cases in the American Joint Replacement Registry (AJRR) suggests it’s the case in the United States as well.

Principal investigator Ryland Kagan, MD, of the department of orthopedic surgery at Oregon Health & Science University in Portland, told this news organization, “What’s unique about our experience in the U.S. is our overall high use of PS implants.”

More than half of TKAs in the United States use the PS bearings; in comparison, in Australia and European countries, PS use is closer to 20%, he said. Because of this disparity, previous studies have not been seen as generalizable to the United States, he said.

Researchers used AJRR data from 2012 to 2019 and identified all primary TKA procedures performed during that period. Cases were linked to supplemental Centers for Medicare & Medicaid Services data to find revision procedures that may not have been included in the AJRR database.

Jamil Kendall, MD, an orthopedic resident at OHSU, was first author on the study. The team evaluated patient demographics, polyethylene characteristics, procedure dates, and cause for revision in the 305,279 cases.

Of those cases in which implant characteristics were reported, 161,486 (52.9%) patients received PS bearings, and 143,793 (47.1%) received minimally stabilized bearings.

The researchers compared three minimally stabilized implants (cruciate retaining [CR], anterior stabilized [AS], or pivot bearing designs) with each other for risk and then compared minimally stabilized options as a group with the PS bearings.

They found no significant differences among the three minimally stabilized options.

But revision risk was higher when they compared the minimally stabilized implants with the PS bearing implants. Use of PS bearings had a hazard ratio of 1.25 (95% confidence interval, 1.2-1.3; P < .0001) for all-cause revision and an HR of 1.18 (95% CI, 1.0-1.4; P = .02) for infection.

Among the patients with minimally stabilized bearings, 1,693 (1.2%) underwent revision for any cause, and 334 (0.2%) underwent revision for infection. For patients with PS bearings, 2,406 (1.5%) underwent revision for any cause, and 446 (0.3%) underwent revision for infection.

Even a small difference significant

Dr. Kagan said, “The difference isn’t dramatic, but when you think of the total number of total knee arthroplasties done, you’re talking about millions of procedures. Even with a small increased risk, you’re going to see a large influence for a population.”

Richard Lynn Illgen, MD, director of the University of Wisconsin-Madison joint replacement program, told this news organization this work identifies a trend, but he pointed out that registry-based studies have important limitations.

“They cannot establish causality,” he said. “There are many potential confounding variables and potential selection biases that could affect the study. Specifically, the study did not control for degree of deformity or medical comorbidities. Although some surgeons routinely use PS designs for all primary TKAs, others use PS designs for patients with more severe deformities. It is possible that PS designs were used more frequently in patients with a greater degree of deformity, and this could introduce a selection bias.”

He added that no data were included to enable stratification of groups according to medical comorbidities.

“It is possible that selection bias exists comparing the relative degree of medical comorbidities between patients in the PS TKA and minimally constrained TKA groups,” Dr. Illgen said.

He said further prospective, randomized studies are needed to eliminate selection bias and to better determine whether the observed pattern of increased risk of revision holds up, compared with the minimally supported versions.

The authors acknowledged those limitations, but Dr. Kagan said the high percentage of PS procedures in the United States helps mitigate potential bias.

Dr. Illgen serves as a consultant and developer for Stryker, is chair of the AAOS AJRR Research Projects Subcommittee, and is a member of the AJRR Steering Committee. Dr. Kagan receives research support from KCI, Ortho Development, and Smith & Nephew, where he is also a paid consultant. Dr. Kendall reports no relevant financial relationships. Another coauthor of the study is a paid consultant for 3M, Heraeus, Immunis, Smith & Nephew, Zimmer Biomet, and Total Joint Orthopedics and has stock or stock options in Joint Development.

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

CHICAGO - Posterior-stabilized (PS) bearings used in total knee arthroplasty (TKA) may increase the risk of revision compared with bearings of other design, new data suggest.

That possibility has previously been reported in studies outside the United States, and now an analysis of more than 300,000 cases in the American Joint Replacement Registry (AJRR) suggests it’s the case in the United States as well.

Principal investigator Ryland Kagan, MD, of the department of orthopedic surgery at Oregon Health & Science University in Portland, told this news organization, “What’s unique about our experience in the U.S. is our overall high use of PS implants.”

More than half of TKAs in the United States use the PS bearings; in comparison, in Australia and European countries, PS use is closer to 20%, he said. Because of this disparity, previous studies have not been seen as generalizable to the United States, he said.

Researchers used AJRR data from 2012 to 2019 and identified all primary TKA procedures performed during that period. Cases were linked to supplemental Centers for Medicare & Medicaid Services data to find revision procedures that may not have been included in the AJRR database.

Jamil Kendall, MD, an orthopedic resident at OHSU, was first author on the study. The team evaluated patient demographics, polyethylene characteristics, procedure dates, and cause for revision in the 305,279 cases.

Of those cases in which implant characteristics were reported, 161,486 (52.9%) patients received PS bearings, and 143,793 (47.1%) received minimally stabilized bearings.

The researchers compared three minimally stabilized implants (cruciate retaining [CR], anterior stabilized [AS], or pivot bearing designs) with each other for risk and then compared minimally stabilized options as a group with the PS bearings.

They found no significant differences among the three minimally stabilized options.

But revision risk was higher when they compared the minimally stabilized implants with the PS bearing implants. Use of PS bearings had a hazard ratio of 1.25 (95% confidence interval, 1.2-1.3; P < .0001) for all-cause revision and an HR of 1.18 (95% CI, 1.0-1.4; P = .02) for infection.

Among the patients with minimally stabilized bearings, 1,693 (1.2%) underwent revision for any cause, and 334 (0.2%) underwent revision for infection. For patients with PS bearings, 2,406 (1.5%) underwent revision for any cause, and 446 (0.3%) underwent revision for infection.

Even a small difference significant

Dr. Kagan said, “The difference isn’t dramatic, but when you think of the total number of total knee arthroplasties done, you’re talking about millions of procedures. Even with a small increased risk, you’re going to see a large influence for a population.”

Richard Lynn Illgen, MD, director of the University of Wisconsin-Madison joint replacement program, told this news organization this work identifies a trend, but he pointed out that registry-based studies have important limitations.

“They cannot establish causality,” he said. “There are many potential confounding variables and potential selection biases that could affect the study. Specifically, the study did not control for degree of deformity or medical comorbidities. Although some surgeons routinely use PS designs for all primary TKAs, others use PS designs for patients with more severe deformities. It is possible that PS designs were used more frequently in patients with a greater degree of deformity, and this could introduce a selection bias.”

He added that no data were included to enable stratification of groups according to medical comorbidities.

“It is possible that selection bias exists comparing the relative degree of medical comorbidities between patients in the PS TKA and minimally constrained TKA groups,” Dr. Illgen said.

He said further prospective, randomized studies are needed to eliminate selection bias and to better determine whether the observed pattern of increased risk of revision holds up, compared with the minimally supported versions.

The authors acknowledged those limitations, but Dr. Kagan said the high percentage of PS procedures in the United States helps mitigate potential bias.

Dr. Illgen serves as a consultant and developer for Stryker, is chair of the AAOS AJRR Research Projects Subcommittee, and is a member of the AJRR Steering Committee. Dr. Kagan receives research support from KCI, Ortho Development, and Smith & Nephew, where he is also a paid consultant. Dr. Kendall reports no relevant financial relationships. Another coauthor of the study is a paid consultant for 3M, Heraeus, Immunis, Smith & Nephew, Zimmer Biomet, and Total Joint Orthopedics and has stock or stock options in Joint Development.

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

CHICAGO - Posterior-stabilized (PS) bearings used in total knee arthroplasty (TKA) may increase the risk of revision compared with bearings of other design, new data suggest.

That possibility has previously been reported in studies outside the United States, and now an analysis of more than 300,000 cases in the American Joint Replacement Registry (AJRR) suggests it’s the case in the United States as well.

Principal investigator Ryland Kagan, MD, of the department of orthopedic surgery at Oregon Health & Science University in Portland, told this news organization, “What’s unique about our experience in the U.S. is our overall high use of PS implants.”

More than half of TKAs in the United States use the PS bearings; in comparison, in Australia and European countries, PS use is closer to 20%, he said. Because of this disparity, previous studies have not been seen as generalizable to the United States, he said.

Researchers used AJRR data from 2012 to 2019 and identified all primary TKA procedures performed during that period. Cases were linked to supplemental Centers for Medicare & Medicaid Services data to find revision procedures that may not have been included in the AJRR database.

Jamil Kendall, MD, an orthopedic resident at OHSU, was first author on the study. The team evaluated patient demographics, polyethylene characteristics, procedure dates, and cause for revision in the 305,279 cases.

Of those cases in which implant characteristics were reported, 161,486 (52.9%) patients received PS bearings, and 143,793 (47.1%) received minimally stabilized bearings.

The researchers compared three minimally stabilized implants (cruciate retaining [CR], anterior stabilized [AS], or pivot bearing designs) with each other for risk and then compared minimally stabilized options as a group with the PS bearings.

They found no significant differences among the three minimally stabilized options.

But revision risk was higher when they compared the minimally stabilized implants with the PS bearing implants. Use of PS bearings had a hazard ratio of 1.25 (95% confidence interval, 1.2-1.3; P < .0001) for all-cause revision and an HR of 1.18 (95% CI, 1.0-1.4; P = .02) for infection.

Among the patients with minimally stabilized bearings, 1,693 (1.2%) underwent revision for any cause, and 334 (0.2%) underwent revision for infection. For patients with PS bearings, 2,406 (1.5%) underwent revision for any cause, and 446 (0.3%) underwent revision for infection.

Even a small difference significant

Dr. Kagan said, “The difference isn’t dramatic, but when you think of the total number of total knee arthroplasties done, you’re talking about millions of procedures. Even with a small increased risk, you’re going to see a large influence for a population.”

Richard Lynn Illgen, MD, director of the University of Wisconsin-Madison joint replacement program, told this news organization this work identifies a trend, but he pointed out that registry-based studies have important limitations.

“They cannot establish causality,” he said. “There are many potential confounding variables and potential selection biases that could affect the study. Specifically, the study did not control for degree of deformity or medical comorbidities. Although some surgeons routinely use PS designs for all primary TKAs, others use PS designs for patients with more severe deformities. It is possible that PS designs were used more frequently in patients with a greater degree of deformity, and this could introduce a selection bias.”

He added that no data were included to enable stratification of groups according to medical comorbidities.

“It is possible that selection bias exists comparing the relative degree of medical comorbidities between patients in the PS TKA and minimally constrained TKA groups,” Dr. Illgen said.

He said further prospective, randomized studies are needed to eliminate selection bias and to better determine whether the observed pattern of increased risk of revision holds up, compared with the minimally supported versions.

The authors acknowledged those limitations, but Dr. Kagan said the high percentage of PS procedures in the United States helps mitigate potential bias.

Dr. Illgen serves as a consultant and developer for Stryker, is chair of the AAOS AJRR Research Projects Subcommittee, and is a member of the AJRR Steering Committee. Dr. Kagan receives research support from KCI, Ortho Development, and Smith & Nephew, where he is also a paid consultant. Dr. Kendall reports no relevant financial relationships. Another coauthor of the study is a paid consultant for 3M, Heraeus, Immunis, Smith & Nephew, Zimmer Biomet, and Total Joint Orthopedics and has stock or stock options in Joint Development.

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

CHICAGO - Patients 80 years or older undergoing primary total knee arthroplasty (TKA) have similar odds of complications, compared with 65- to 79-year-old patients, an analysis of more than 1.7 million cases suggests.

Priscilla Varghese, MBA, MS, and an MD candidate at State University of New York, Brooklyn, led the research, presented at the American Academy of Orthopaedic Surgeons 2022 annual meeting.

Ms. Varghese’s team queried a Medicare claims database for the years 2005-2014 and analyzed information from 295,908 octogenarians and 1.4 million control patients aged 65-79 who received TKA.

Study group patients were randomly matched to controls in a 1:5 ratio according to gender and comorbidities, including chronic obstructive pulmonary disease, congestive heart failure, diabetes, peripheral vascular disease, and kidney failure.

Octogenarians were found to have higher incidence and odds of 90-day readmission rates (10.59% vs. 9.35%; odds ratio, 1.15; 95% confidence interval, 1.13-1.16; P < .0001).   

Hospital stays were also longer (3.69 days ± 1.95 vs. 3.23 days ± 1.83; P < .0001), compared with controls.

Reassuring older patients

However, Ms. Varghese told this news organization she was surprised to find that the older group had equal incidence and odds of developing medical complications (1.26% vs. 1.26%; OR, 0.99; 95% CI, 0.96-1.03; P =.99).

“That’s a really important piece of information to have when we are advising 80-year-olds – to be able to say their risk of adverse outcomes is similar to someone who’s 10 years, 15 years younger,” she said. “It’s really reassuring.”

These results offer good news to older patients who might be hesitant to undergo the surgery, and good news in general as life expectancy increases and people stay active long into their later years, forecasting the need for more knee replacements.

The number of total knee replacements is expected to rise dramatically in the United States.

In a 2017 study published in Osteoarthritis Cartilage, the authors write, “the number of TKAs in the U.S., which already has the highest [incidence rate] of knee arthroplasty in the world, is expected to increase 143% by 2050.”

Thomas Fleeter, MD, an orthopedic surgeon practicing in Reston, Virginia, who was not involved in the study, told this news organization this study reinforces that “it’s OK to do knee replacements in elderly people; you just have to pick the right ones.”

He pointed out that the study also showed that the 80-and-older patients don’t have the added risk of loosening their mechanical components after the surgery, likely because they are less inclined than their younger counterparts to follow surgery with strenuous activities.

In a subanalysis, revision rates were also lower for the octogenarians (0.01% vs. 0.02% for controls).

Octogenarians who had TKA were found to have lower incidence and odds (1.6% vs. 1.93%; OR, 0.86; 95% CI, 0.83-0.88, P < .001) of implant-related complications, compared with the younger group.

The increased length of stay would be expected, Dr. Fleeter said, because those 80-plus may need a bit more help getting out of bed and may not have as much support at home.

A total knee replacement can have the substantial benefit of improving octogenarians’ ability to maintain their independence longer by facilitating driving or walking.

“It’s a small and manageable risk if you pick the right patients,” he said.

Demand for TKAs rises as population ages

As patients are living longer and wanting to maintain their mobility and as obesity rates are rising, more older patients will seek total knee replacements, especially since the payoff is high, Ms. Varghese noted.

“People who undergo this operation tend to show remarkable decreases in pain and increases in range of motion,” she said.

This study has the advantage of a more personalized look at risks of TKA because it stratifies age groups.

“The literature tends to look at the elderly population as one big cohort – 65 and older,” Ms. Varghese said. “We were able to provide patients more specific data.”

Ms. Varghese and Dr. Fleeter have disclosed no relevant financial relationships.

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

CHICAGO - Patients 80 years or older undergoing primary total knee arthroplasty (TKA) have similar odds of complications, compared with 65- to 79-year-old patients, an analysis of more than 1.7 million cases suggests.

Priscilla Varghese, MBA, MS, and an MD candidate at State University of New York, Brooklyn, led the research, presented at the American Academy of Orthopaedic Surgeons 2022 annual meeting.

Ms. Varghese’s team queried a Medicare claims database for the years 2005-2014 and analyzed information from 295,908 octogenarians and 1.4 million control patients aged 65-79 who received TKA.

Study group patients were randomly matched to controls in a 1:5 ratio according to gender and comorbidities, including chronic obstructive pulmonary disease, congestive heart failure, diabetes, peripheral vascular disease, and kidney failure.

Octogenarians were found to have higher incidence and odds of 90-day readmission rates (10.59% vs. 9.35%; odds ratio, 1.15; 95% confidence interval, 1.13-1.16; P < .0001).   

Hospital stays were also longer (3.69 days ± 1.95 vs. 3.23 days ± 1.83; P < .0001), compared with controls.

Reassuring older patients

However, Ms. Varghese told this news organization she was surprised to find that the older group had equal incidence and odds of developing medical complications (1.26% vs. 1.26%; OR, 0.99; 95% CI, 0.96-1.03; P =.99).

“That’s a really important piece of information to have when we are advising 80-year-olds – to be able to say their risk of adverse outcomes is similar to someone who’s 10 years, 15 years younger,” she said. “It’s really reassuring.”

These results offer good news to older patients who might be hesitant to undergo the surgery, and good news in general as life expectancy increases and people stay active long into their later years, forecasting the need for more knee replacements.

The number of total knee replacements is expected to rise dramatically in the United States.

In a 2017 study published in Osteoarthritis Cartilage, the authors write, “the number of TKAs in the U.S., which already has the highest [incidence rate] of knee arthroplasty in the world, is expected to increase 143% by 2050.”

Thomas Fleeter, MD, an orthopedic surgeon practicing in Reston, Virginia, who was not involved in the study, told this news organization this study reinforces that “it’s OK to do knee replacements in elderly people; you just have to pick the right ones.”

He pointed out that the study also showed that the 80-and-older patients don’t have the added risk of loosening their mechanical components after the surgery, likely because they are less inclined than their younger counterparts to follow surgery with strenuous activities.

In a subanalysis, revision rates were also lower for the octogenarians (0.01% vs. 0.02% for controls).

Octogenarians who had TKA were found to have lower incidence and odds (1.6% vs. 1.93%; OR, 0.86; 95% CI, 0.83-0.88, P < .001) of implant-related complications, compared with the younger group.

The increased length of stay would be expected, Dr. Fleeter said, because those 80-plus may need a bit more help getting out of bed and may not have as much support at home.

A total knee replacement can have the substantial benefit of improving octogenarians’ ability to maintain their independence longer by facilitating driving or walking.

“It’s a small and manageable risk if you pick the right patients,” he said.

Demand for TKAs rises as population ages

As patients are living longer and wanting to maintain their mobility and as obesity rates are rising, more older patients will seek total knee replacements, especially since the payoff is high, Ms. Varghese noted.

“People who undergo this operation tend to show remarkable decreases in pain and increases in range of motion,” she said.

This study has the advantage of a more personalized look at risks of TKA because it stratifies age groups.

“The literature tends to look at the elderly population as one big cohort – 65 and older,” Ms. Varghese said. “We were able to provide patients more specific data.”

Ms. Varghese and Dr. Fleeter have disclosed no relevant financial relationships.

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

CHICAGO - Patients 80 years or older undergoing primary total knee arthroplasty (TKA) have similar odds of complications, compared with 65- to 79-year-old patients, an analysis of more than 1.7 million cases suggests.

Priscilla Varghese, MBA, MS, and an MD candidate at State University of New York, Brooklyn, led the research, presented at the American Academy of Orthopaedic Surgeons 2022 annual meeting.

Ms. Varghese’s team queried a Medicare claims database for the years 2005-2014 and analyzed information from 295,908 octogenarians and 1.4 million control patients aged 65-79 who received TKA.

Study group patients were randomly matched to controls in a 1:5 ratio according to gender and comorbidities, including chronic obstructive pulmonary disease, congestive heart failure, diabetes, peripheral vascular disease, and kidney failure.

Octogenarians were found to have higher incidence and odds of 90-day readmission rates (10.59% vs. 9.35%; odds ratio, 1.15; 95% confidence interval, 1.13-1.16; P < .0001).   

Hospital stays were also longer (3.69 days ± 1.95 vs. 3.23 days ± 1.83; P < .0001), compared with controls.

Reassuring older patients

However, Ms. Varghese told this news organization she was surprised to find that the older group had equal incidence and odds of developing medical complications (1.26% vs. 1.26%; OR, 0.99; 95% CI, 0.96-1.03; P =.99).

“That’s a really important piece of information to have when we are advising 80-year-olds – to be able to say their risk of adverse outcomes is similar to someone who’s 10 years, 15 years younger,” she said. “It’s really reassuring.”

These results offer good news to older patients who might be hesitant to undergo the surgery, and good news in general as life expectancy increases and people stay active long into their later years, forecasting the need for more knee replacements.

The number of total knee replacements is expected to rise dramatically in the United States.

In a 2017 study published in Osteoarthritis Cartilage, the authors write, “the number of TKAs in the U.S., which already has the highest [incidence rate] of knee arthroplasty in the world, is expected to increase 143% by 2050.”

Thomas Fleeter, MD, an orthopedic surgeon practicing in Reston, Virginia, who was not involved in the study, told this news organization this study reinforces that “it’s OK to do knee replacements in elderly people; you just have to pick the right ones.”

He pointed out that the study also showed that the 80-and-older patients don’t have the added risk of loosening their mechanical components after the surgery, likely because they are less inclined than their younger counterparts to follow surgery with strenuous activities.

In a subanalysis, revision rates were also lower for the octogenarians (0.01% vs. 0.02% for controls).

Octogenarians who had TKA were found to have lower incidence and odds (1.6% vs. 1.93%; OR, 0.86; 95% CI, 0.83-0.88, P < .001) of implant-related complications, compared with the younger group.

The increased length of stay would be expected, Dr. Fleeter said, because those 80-plus may need a bit more help getting out of bed and may not have as much support at home.

A total knee replacement can have the substantial benefit of improving octogenarians’ ability to maintain their independence longer by facilitating driving or walking.

“It’s a small and manageable risk if you pick the right patients,” he said.

Demand for TKAs rises as population ages

As patients are living longer and wanting to maintain their mobility and as obesity rates are rising, more older patients will seek total knee replacements, especially since the payoff is high, Ms. Varghese noted.

“People who undergo this operation tend to show remarkable decreases in pain and increases in range of motion,” she said.

This study has the advantage of a more personalized look at risks of TKA because it stratifies age groups.

“The literature tends to look at the elderly population as one big cohort – 65 and older,” Ms. Varghese said. “We were able to provide patients more specific data.”

Ms. Varghese and Dr. Fleeter have disclosed no relevant financial relationships.

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

WASHINGTON – Probiotics are generally used in relatively nontargeted, nonspecific ways. But with the gut microbiome being an integral component of a budding precision medicine model of care, and with “multi-omics” research picking up, this is bound to change, gastroenterologist Purna C. Kashyap, MBBS, said in an interview after the 2022 Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association and the European Society of Neurogastroenterology and Motility.

“There are so many missing pieces of information because, at the very basic level, we don’t know exactly how gut bacteria drive diseases,” he told GI & Hepatology News.

“The idea is to go toward a more precise, accurate approach where the newer generation of probiotics are designed to target a specific process, like block a microbial pathway that contributes to disease pathogenesis, or produce a metabolite that improves host function,” he said. “It’s this shift that is going on in the field. It’s already started, and it has momentum.” Dr. Kashyap is a professor of medicine and physiology at the Mayo Clinic College of Medicine in Rochester, Minn., and codirector of the institution’s microbiome program.

In a keynote lecture at the meeting, Dr. Kashyap said that the current approach to precision medicine, which aims to tailor treatments to defined subgroups of patients, needs to take into account “much more than the human genome.”

To the extent possible, it needs to consider the host (lifestyle, gene variants, etc.), the microbiome, and the exposome (environmental exposures such as diet, medications, and air and water quality).

The microbiome’s relative contribution to any one disease, in turn, likely varies from one individual or subgroup to another, he said.

Researchers are increasingly working with different layers of data and using machine learning methods and artificial intelligence approaches to integrate clinical data and “omics” measurements (e.g., from genome, proteome, metabolome).

Such approaches can help pinpoint the microbiome’s relative contributions, identify microbial-host behaviors and microbial-driven disease mechanisms, and ultimately personalize treatment approaches, Dr. Kashyap said.

For instance, Dr. Kashyap’s team has taken a multi-omics approach to studying patients with irritable bowel syndrome (IBS). Thus far, their research has identified subtype-specific variation in microbial composition and function, and by integrating omics from the host and microbiome, it has confirmed the role of several microbial pathways in subtypes of IBS.

His team has also identified a new pathway – the host and gut microbiota’s modulation of purine metabolism – as a potential driver of symptoms in patients with IBS (Cell 2020;182[6]:1460-73), he said.

Such findings provide opportunities to develop new microbial therapeutics – by engineering bacteria to produce metabolites that target a specific pathway, for instance, he said.
 

Predicting probiotic engraftment

Understanding the extent to which microbes actually engraft in the gut – and the forces governing engraftment – is part of a rational approach to designing future probiotic cocktails and to moving toward personalized, precision medicine, Eric Alm, PhD, said during a plenary session on the future of probiotics, moderated by Dr. Kashyap. Dr. Alm is a professor of biological, civil, and environmental engineering who directs the Center for Microbiome Informatics and Therapeutics at the Massachusetts Institute of Technology in Cambridge.

“One of the best datasets we have when thinking about designing therapeutic microbes is FMT (fecal microbiota transplant) data” in patients with Clostridioides difficile infection (CDI), said Dr. Alm.

“We wondered, can you predict what a patient will look like post FMT given what they looked like before and given what the donor looks like?” he said. “We found that engraftment can be predicted surprisingly well.”

Using computational algorithms and metagenomics sequencing data from donors and recipients, the researchers found that engraftment can be predicted largely from the abundance and strains of bacteria in the donor and the pre-FMT patient microbiome (Cell Host Microbe 2018;23[2]:229-40.e5).

They also observed two behaviors: Previously undetected strains (not transplanted) frequently show up in patients who received FMT, and all donor strains within a species engrafted in an all-or-nothing fashion.

“Seeding a patient with a new species allows them to collect more strains of that species from the environment – this is fairly common,” said Dr. Alm. “But if I give five different strains of Faecalibacterium prausnitzii to a patient who doesn’t have any, they’ll get either zero, or they’ll get all five ... this is an observation we don’t fully understand yet.”

These types of observations “guide our thinking in how to produce rationally designed cocktails,” he said.
 

Other approaches to probiotics

In another type of research, Philippe Langella, PhD, who leads a laboratory of Commensal and Probiotics-Host Interactions at the Micalis Institute in France, has been investigating the use of genetically modified lactic acid bacteria to deliver anti-proteases and other types of molecules to patients with disease, such as the antiprotease elafin to patients with inflammatory bowel disease (IBD).

There is “a lack of elafin in Crohn’s disease and ulcerative colitis patients,” Dr. Langella said during the plenary session. “The idea is to use the genetically modified lactic acid bacteria to counterbalance the protease-antiprotease imbalance in IBD.”

In animal and in vitro models, elafin-expressing lactic acid bacteria decreased elastolytic activity and inflammation in the gut and restored intestinal permeability. The goal now, he said, is to construct biologically contained strains of the engineered bacteria to test in clinical trials.

While today’s probiotics are generally considered to be safe and to have beneficial effects, the next generation will be more targeted – more “rational,“ Dr. Kashyap said in his interview. Each of these researchers,” he said, “is working on different pieces of the puzzle and, eventually, this will allow us to accelerate the development of novel therapies.”

Dr. Kashyap said he has no disclosures relevant to his keynote address or moderation of the plenary session. In his presentation, Dr. Alm disclosed his involvement with Finch Therapeutics, OpenBiome, and Biobot Analytics.

Dr. Langella disclosed in his presentation that he is co-founder of Exeliom Biosciences and has research grants with various pharmaceutical companies, food supplement companies, and agro-food companies.

The 2022 Gut Microbiota for Health World Summit was supported by sponsorships from Danone, Ferring Pharmaceuticals, Aimmune Therapeutics and Seres Therapeutics, Sanofi, and Intrinsic Medicine Inc. with additional support from educational grants provided by Ferring Pharmaceuticals and Salix Pharmaceuticals.

This article was updated 4/5/22.

WASHINGTON – Probiotics are generally used in relatively nontargeted, nonspecific ways. But with the gut microbiome being an integral component of a budding precision medicine model of care, and with “multi-omics” research picking up, this is bound to change, gastroenterologist Purna C. Kashyap, MBBS, said in an interview after the 2022 Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association and the European Society of Neurogastroenterology and Motility.

“There are so many missing pieces of information because, at the very basic level, we don’t know exactly how gut bacteria drive diseases,” he told GI & Hepatology News.

“The idea is to go toward a more precise, accurate approach where the newer generation of probiotics are designed to target a specific process, like block a microbial pathway that contributes to disease pathogenesis, or produce a metabolite that improves host function,” he said. “It’s this shift that is going on in the field. It’s already started, and it has momentum.” Dr. Kashyap is a professor of medicine and physiology at the Mayo Clinic College of Medicine in Rochester, Minn., and codirector of the institution’s microbiome program.

In a keynote lecture at the meeting, Dr. Kashyap said that the current approach to precision medicine, which aims to tailor treatments to defined subgroups of patients, needs to take into account “much more than the human genome.”

To the extent possible, it needs to consider the host (lifestyle, gene variants, etc.), the microbiome, and the exposome (environmental exposures such as diet, medications, and air and water quality).

The microbiome’s relative contribution to any one disease, in turn, likely varies from one individual or subgroup to another, he said.

Researchers are increasingly working with different layers of data and using machine learning methods and artificial intelligence approaches to integrate clinical data and “omics” measurements (e.g., from genome, proteome, metabolome).

Such approaches can help pinpoint the microbiome’s relative contributions, identify microbial-host behaviors and microbial-driven disease mechanisms, and ultimately personalize treatment approaches, Dr. Kashyap said.

For instance, Dr. Kashyap’s team has taken a multi-omics approach to studying patients with irritable bowel syndrome (IBS). Thus far, their research has identified subtype-specific variation in microbial composition and function, and by integrating omics from the host and microbiome, it has confirmed the role of several microbial pathways in subtypes of IBS.

His team has also identified a new pathway – the host and gut microbiota’s modulation of purine metabolism – as a potential driver of symptoms in patients with IBS (Cell 2020;182[6]:1460-73), he said.

Such findings provide opportunities to develop new microbial therapeutics – by engineering bacteria to produce metabolites that target a specific pathway, for instance, he said.
 

Predicting probiotic engraftment

Understanding the extent to which microbes actually engraft in the gut – and the forces governing engraftment – is part of a rational approach to designing future probiotic cocktails and to moving toward personalized, precision medicine, Eric Alm, PhD, said during a plenary session on the future of probiotics, moderated by Dr. Kashyap. Dr. Alm is a professor of biological, civil, and environmental engineering who directs the Center for Microbiome Informatics and Therapeutics at the Massachusetts Institute of Technology in Cambridge.

“One of the best datasets we have when thinking about designing therapeutic microbes is FMT (fecal microbiota transplant) data” in patients with Clostridioides difficile infection (CDI), said Dr. Alm.

“We wondered, can you predict what a patient will look like post FMT given what they looked like before and given what the donor looks like?” he said. “We found that engraftment can be predicted surprisingly well.”

Using computational algorithms and metagenomics sequencing data from donors and recipients, the researchers found that engraftment can be predicted largely from the abundance and strains of bacteria in the donor and the pre-FMT patient microbiome (Cell Host Microbe 2018;23[2]:229-40.e5).

They also observed two behaviors: Previously undetected strains (not transplanted) frequently show up in patients who received FMT, and all donor strains within a species engrafted in an all-or-nothing fashion.

“Seeding a patient with a new species allows them to collect more strains of that species from the environment – this is fairly common,” said Dr. Alm. “But if I give five different strains of Faecalibacterium prausnitzii to a patient who doesn’t have any, they’ll get either zero, or they’ll get all five ... this is an observation we don’t fully understand yet.”

These types of observations “guide our thinking in how to produce rationally designed cocktails,” he said.
 

Other approaches to probiotics

In another type of research, Philippe Langella, PhD, who leads a laboratory of Commensal and Probiotics-Host Interactions at the Micalis Institute in France, has been investigating the use of genetically modified lactic acid bacteria to deliver anti-proteases and other types of molecules to patients with disease, such as the antiprotease elafin to patients with inflammatory bowel disease (IBD).

There is “a lack of elafin in Crohn’s disease and ulcerative colitis patients,” Dr. Langella said during the plenary session. “The idea is to use the genetically modified lactic acid bacteria to counterbalance the protease-antiprotease imbalance in IBD.”

In animal and in vitro models, elafin-expressing lactic acid bacteria decreased elastolytic activity and inflammation in the gut and restored intestinal permeability. The goal now, he said, is to construct biologically contained strains of the engineered bacteria to test in clinical trials.

While today’s probiotics are generally considered to be safe and to have beneficial effects, the next generation will be more targeted – more “rational,“ Dr. Kashyap said in his interview. Each of these researchers,” he said, “is working on different pieces of the puzzle and, eventually, this will allow us to accelerate the development of novel therapies.”

Dr. Kashyap said he has no disclosures relevant to his keynote address or moderation of the plenary session. In his presentation, Dr. Alm disclosed his involvement with Finch Therapeutics, OpenBiome, and Biobot Analytics.

Dr. Langella disclosed in his presentation that he is co-founder of Exeliom Biosciences and has research grants with various pharmaceutical companies, food supplement companies, and agro-food companies.

The 2022 Gut Microbiota for Health World Summit was supported by sponsorships from Danone, Ferring Pharmaceuticals, Aimmune Therapeutics and Seres Therapeutics, Sanofi, and Intrinsic Medicine Inc. with additional support from educational grants provided by Ferring Pharmaceuticals and Salix Pharmaceuticals.

This article was updated 4/5/22.

WASHINGTON – Probiotics are generally used in relatively nontargeted, nonspecific ways. But with the gut microbiome being an integral component of a budding precision medicine model of care, and with “multi-omics” research picking up, this is bound to change, gastroenterologist Purna C. Kashyap, MBBS, said in an interview after the 2022 Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association and the European Society of Neurogastroenterology and Motility.

“There are so many missing pieces of information because, at the very basic level, we don’t know exactly how gut bacteria drive diseases,” he told GI & Hepatology News.

“The idea is to go toward a more precise, accurate approach where the newer generation of probiotics are designed to target a specific process, like block a microbial pathway that contributes to disease pathogenesis, or produce a metabolite that improves host function,” he said. “It’s this shift that is going on in the field. It’s already started, and it has momentum.” Dr. Kashyap is a professor of medicine and physiology at the Mayo Clinic College of Medicine in Rochester, Minn., and codirector of the institution’s microbiome program.

In a keynote lecture at the meeting, Dr. Kashyap said that the current approach to precision medicine, which aims to tailor treatments to defined subgroups of patients, needs to take into account “much more than the human genome.”

To the extent possible, it needs to consider the host (lifestyle, gene variants, etc.), the microbiome, and the exposome (environmental exposures such as diet, medications, and air and water quality).

The microbiome’s relative contribution to any one disease, in turn, likely varies from one individual or subgroup to another, he said.

Researchers are increasingly working with different layers of data and using machine learning methods and artificial intelligence approaches to integrate clinical data and “omics” measurements (e.g., from genome, proteome, metabolome).

Such approaches can help pinpoint the microbiome’s relative contributions, identify microbial-host behaviors and microbial-driven disease mechanisms, and ultimately personalize treatment approaches, Dr. Kashyap said.

For instance, Dr. Kashyap’s team has taken a multi-omics approach to studying patients with irritable bowel syndrome (IBS). Thus far, their research has identified subtype-specific variation in microbial composition and function, and by integrating omics from the host and microbiome, it has confirmed the role of several microbial pathways in subtypes of IBS.

His team has also identified a new pathway – the host and gut microbiota’s modulation of purine metabolism – as a potential driver of symptoms in patients with IBS (Cell 2020;182[6]:1460-73), he said.

Such findings provide opportunities to develop new microbial therapeutics – by engineering bacteria to produce metabolites that target a specific pathway, for instance, he said.
 

Predicting probiotic engraftment

Understanding the extent to which microbes actually engraft in the gut – and the forces governing engraftment – is part of a rational approach to designing future probiotic cocktails and to moving toward personalized, precision medicine, Eric Alm, PhD, said during a plenary session on the future of probiotics, moderated by Dr. Kashyap. Dr. Alm is a professor of biological, civil, and environmental engineering who directs the Center for Microbiome Informatics and Therapeutics at the Massachusetts Institute of Technology in Cambridge.

“One of the best datasets we have when thinking about designing therapeutic microbes is FMT (fecal microbiota transplant) data” in patients with Clostridioides difficile infection (CDI), said Dr. Alm.

“We wondered, can you predict what a patient will look like post FMT given what they looked like before and given what the donor looks like?” he said. “We found that engraftment can be predicted surprisingly well.”

Using computational algorithms and metagenomics sequencing data from donors and recipients, the researchers found that engraftment can be predicted largely from the abundance and strains of bacteria in the donor and the pre-FMT patient microbiome (Cell Host Microbe 2018;23[2]:229-40.e5).

They also observed two behaviors: Previously undetected strains (not transplanted) frequently show up in patients who received FMT, and all donor strains within a species engrafted in an all-or-nothing fashion.

“Seeding a patient with a new species allows them to collect more strains of that species from the environment – this is fairly common,” said Dr. Alm. “But if I give five different strains of Faecalibacterium prausnitzii to a patient who doesn’t have any, they’ll get either zero, or they’ll get all five ... this is an observation we don’t fully understand yet.”

These types of observations “guide our thinking in how to produce rationally designed cocktails,” he said.
 

Other approaches to probiotics

In another type of research, Philippe Langella, PhD, who leads a laboratory of Commensal and Probiotics-Host Interactions at the Micalis Institute in France, has been investigating the use of genetically modified lactic acid bacteria to deliver anti-proteases and other types of molecules to patients with disease, such as the antiprotease elafin to patients with inflammatory bowel disease (IBD).

There is “a lack of elafin in Crohn’s disease and ulcerative colitis patients,” Dr. Langella said during the plenary session. “The idea is to use the genetically modified lactic acid bacteria to counterbalance the protease-antiprotease imbalance in IBD.”

In animal and in vitro models, elafin-expressing lactic acid bacteria decreased elastolytic activity and inflammation in the gut and restored intestinal permeability. The goal now, he said, is to construct biologically contained strains of the engineered bacteria to test in clinical trials.

While today’s probiotics are generally considered to be safe and to have beneficial effects, the next generation will be more targeted – more “rational,“ Dr. Kashyap said in his interview. Each of these researchers,” he said, “is working on different pieces of the puzzle and, eventually, this will allow us to accelerate the development of novel therapies.”

Dr. Kashyap said he has no disclosures relevant to his keynote address or moderation of the plenary session. In his presentation, Dr. Alm disclosed his involvement with Finch Therapeutics, OpenBiome, and Biobot Analytics.

Dr. Langella disclosed in his presentation that he is co-founder of Exeliom Biosciences and has research grants with various pharmaceutical companies, food supplement companies, and agro-food companies.

The 2022 Gut Microbiota for Health World Summit was supported by sponsorships from Danone, Ferring Pharmaceuticals, Aimmune Therapeutics and Seres Therapeutics, Sanofi, and Intrinsic Medicine Inc. with additional support from educational grants provided by Ferring Pharmaceuticals and Salix Pharmaceuticals.

This article was updated 4/5/22.

Perioperative immunotherapy appears to be safe in the setting of resectable hepatocellular carcinoma (HCC), according to findings from an open-label phase 2 clinical trial published in The Lancet Gastroenterology and Hepatolgy.

The study compared the anti-PD1 antibody nivolumab (Opdivo, Bristol Myers Squibb) alone and nivolumab plus the anti-CTLA-4 antibody ipilimumab (Yervoy, Bristol Myers Squibb) among patients with resectable disease at a single center in Sweden. The treatments were found to be “safe and feasible in patients with resectable hepatocellular carcinoma,” wrote researchers who were led by Ahmed O. Kaseb, MD, a medical oncologist with MD Anderson Cancer Center, Houston.

The rate of 5-year tumor recurrence following HCC resection can be as high as 70%, and there are no approved neoadjuvant or adjuvant therapies.

Immune checkpoint therapy has not been well studied in early-stage HCC, but it is used in advanced HCC.

The combination of PDL1 blockade with atezolizumab and VEGF blockade with bevacizumab, is currently a first-line treatment for advanced HCC. “Checkpoint inhibitors targeting PD1 and PDL1 and CTLA4 are active, tolerable, and clinically beneficial against advanced HCC,” according to researchers writing in a Nature Reviews article published in April 2021.

There are other promising immunotherapies under study for HCC, such as additional checkpoint inhibitors, adoptive cell transfer, vaccination, and virotherapy.
 

Small study of 27 patients

The Lancet study included 27 patients (64 years mean age, 19 patients were male). Twenty-three percent of patients on nivolumab alone had a partial pathological response at week 6, while none in the combination group had a response. Among 20 patients who underwent surgery, 3 of 9 (33%) and 3 of 11 (27%) in the combination group experienced a major pathological response. Two patients in the nivolumab and three patients in the combination group achieved a complete pathological response.

Disease progression occurred in 7 of 12 patients who were evaluated in the nivolumab group, and 4 of 13 patients in the combination group. Estimated median time to disease progression in the nivolumab group was 9.4 months (95% confidence interval, 1.47 to not estimable) and 19.53 months (95% CI, 2.33 to not estimable) in the combination group. Two-year progression-free survival was estimated to be 42% (95% CI, 21%-81%) in the nivolumab group and 26% (95% CI, 8%-78%, no significant difference) in the combination group.

Among 20 patients who underwent surgery, 6 patients had experienced a major pathological response. None of the 6 patients had a recurrence after a median follow-up of 26.8 months, versus 7 recurrences among 14 patients without a pathological response (log-rank P = .049).

Seventy-seven percent of patients in the nivolumab group experienced at least one adverse event (23% grade 3-4), as did 86% in the combination group (43% grade 3-4, difference nonsignificant). No patients delayed or canceled surgery because of adverse events.

Patients who had a major pathological response on the combination treatment had higher levels of immune infiltration versus baseline values. Those who had complete pathological responses in the nivolumab group had high infiltration at baseline. Those results imply some optimism for further study. “These data suggest that, with the immune-priming ability of anti–CTLA-4 treatment, nivolumab plus ipilimumab was able to generate a major pathological response even in tumours that had low immune infiltration at baseline,” the authors wrote.

The study was limited by its open-label nature and small sample size, and it was conducted at a single center.

The study was funded by Bristol Myers Squibb and the National Institutes of Health. Dr. Kaseb reports consulting, advisory roles or stock ownership, or both with Bristol-Myers Squibb.
 

Perioperative immunotherapy appears to be safe in the setting of resectable hepatocellular carcinoma (HCC), according to findings from an open-label phase 2 clinical trial published in The Lancet Gastroenterology and Hepatolgy.

The study compared the anti-PD1 antibody nivolumab (Opdivo, Bristol Myers Squibb) alone and nivolumab plus the anti-CTLA-4 antibody ipilimumab (Yervoy, Bristol Myers Squibb) among patients with resectable disease at a single center in Sweden. The treatments were found to be “safe and feasible in patients with resectable hepatocellular carcinoma,” wrote researchers who were led by Ahmed O. Kaseb, MD, a medical oncologist with MD Anderson Cancer Center, Houston.

The rate of 5-year tumor recurrence following HCC resection can be as high as 70%, and there are no approved neoadjuvant or adjuvant therapies.

Immune checkpoint therapy has not been well studied in early-stage HCC, but it is used in advanced HCC.

The combination of PDL1 blockade with atezolizumab and VEGF blockade with bevacizumab, is currently a first-line treatment for advanced HCC. “Checkpoint inhibitors targeting PD1 and PDL1 and CTLA4 are active, tolerable, and clinically beneficial against advanced HCC,” according to researchers writing in a Nature Reviews article published in April 2021.

There are other promising immunotherapies under study for HCC, such as additional checkpoint inhibitors, adoptive cell transfer, vaccination, and virotherapy.
 

Small study of 27 patients

The Lancet study included 27 patients (64 years mean age, 19 patients were male). Twenty-three percent of patients on nivolumab alone had a partial pathological response at week 6, while none in the combination group had a response. Among 20 patients who underwent surgery, 3 of 9 (33%) and 3 of 11 (27%) in the combination group experienced a major pathological response. Two patients in the nivolumab and three patients in the combination group achieved a complete pathological response.

Disease progression occurred in 7 of 12 patients who were evaluated in the nivolumab group, and 4 of 13 patients in the combination group. Estimated median time to disease progression in the nivolumab group was 9.4 months (95% confidence interval, 1.47 to not estimable) and 19.53 months (95% CI, 2.33 to not estimable) in the combination group. Two-year progression-free survival was estimated to be 42% (95% CI, 21%-81%) in the nivolumab group and 26% (95% CI, 8%-78%, no significant difference) in the combination group.

Among 20 patients who underwent surgery, 6 patients had experienced a major pathological response. None of the 6 patients had a recurrence after a median follow-up of 26.8 months, versus 7 recurrences among 14 patients without a pathological response (log-rank P = .049).

Seventy-seven percent of patients in the nivolumab group experienced at least one adverse event (23% grade 3-4), as did 86% in the combination group (43% grade 3-4, difference nonsignificant). No patients delayed or canceled surgery because of adverse events.

Patients who had a major pathological response on the combination treatment had higher levels of immune infiltration versus baseline values. Those who had complete pathological responses in the nivolumab group had high infiltration at baseline. Those results imply some optimism for further study. “These data suggest that, with the immune-priming ability of anti–CTLA-4 treatment, nivolumab plus ipilimumab was able to generate a major pathological response even in tumours that had low immune infiltration at baseline,” the authors wrote.

The study was limited by its open-label nature and small sample size, and it was conducted at a single center.

The study was funded by Bristol Myers Squibb and the National Institutes of Health. Dr. Kaseb reports consulting, advisory roles or stock ownership, or both with Bristol-Myers Squibb.
 

Perioperative immunotherapy appears to be safe in the setting of resectable hepatocellular carcinoma (HCC), according to findings from an open-label phase 2 clinical trial published in The Lancet Gastroenterology and Hepatolgy.

The study compared the anti-PD1 antibody nivolumab (Opdivo, Bristol Myers Squibb) alone and nivolumab plus the anti-CTLA-4 antibody ipilimumab (Yervoy, Bristol Myers Squibb) among patients with resectable disease at a single center in Sweden. The treatments were found to be “safe and feasible in patients with resectable hepatocellular carcinoma,” wrote researchers who were led by Ahmed O. Kaseb, MD, a medical oncologist with MD Anderson Cancer Center, Houston.

The rate of 5-year tumor recurrence following HCC resection can be as high as 70%, and there are no approved neoadjuvant or adjuvant therapies.

Immune checkpoint therapy has not been well studied in early-stage HCC, but it is used in advanced HCC.

The combination of PDL1 blockade with atezolizumab and VEGF blockade with bevacizumab, is currently a first-line treatment for advanced HCC. “Checkpoint inhibitors targeting PD1 and PDL1 and CTLA4 are active, tolerable, and clinically beneficial against advanced HCC,” according to researchers writing in a Nature Reviews article published in April 2021.

There are other promising immunotherapies under study for HCC, such as additional checkpoint inhibitors, adoptive cell transfer, vaccination, and virotherapy.
 

Small study of 27 patients

The Lancet study included 27 patients (64 years mean age, 19 patients were male). Twenty-three percent of patients on nivolumab alone had a partial pathological response at week 6, while none in the combination group had a response. Among 20 patients who underwent surgery, 3 of 9 (33%) and 3 of 11 (27%) in the combination group experienced a major pathological response. Two patients in the nivolumab and three patients in the combination group achieved a complete pathological response.

Disease progression occurred in 7 of 12 patients who were evaluated in the nivolumab group, and 4 of 13 patients in the combination group. Estimated median time to disease progression in the nivolumab group was 9.4 months (95% confidence interval, 1.47 to not estimable) and 19.53 months (95% CI, 2.33 to not estimable) in the combination group. Two-year progression-free survival was estimated to be 42% (95% CI, 21%-81%) in the nivolumab group and 26% (95% CI, 8%-78%, no significant difference) in the combination group.

Among 20 patients who underwent surgery, 6 patients had experienced a major pathological response. None of the 6 patients had a recurrence after a median follow-up of 26.8 months, versus 7 recurrences among 14 patients without a pathological response (log-rank P = .049).

Seventy-seven percent of patients in the nivolumab group experienced at least one adverse event (23% grade 3-4), as did 86% in the combination group (43% grade 3-4, difference nonsignificant). No patients delayed or canceled surgery because of adverse events.

Patients who had a major pathological response on the combination treatment had higher levels of immune infiltration versus baseline values. Those who had complete pathological responses in the nivolumab group had high infiltration at baseline. Those results imply some optimism for further study. “These data suggest that, with the immune-priming ability of anti–CTLA-4 treatment, nivolumab plus ipilimumab was able to generate a major pathological response even in tumours that had low immune infiltration at baseline,” the authors wrote.

The study was limited by its open-label nature and small sample size, and it was conducted at a single center.

The study was funded by Bristol Myers Squibb and the National Institutes of Health. Dr. Kaseb reports consulting, advisory roles or stock ownership, or both with Bristol-Myers Squibb.
 

What are the principal microorganisms that cause puerperal mastitis?

Continue to the answer...

Staphylococci and Streptococcus viridans are the 2 dominant microorganisms that cause puerperal mastitis. For the initial treatment of mastitis, the drug of choice is dicloxacillin sodium (500 mg orally every 6 to 8 hours for 7 to 10 days). If the patient has a mild allergy to penicillin, cephalexin (500 mg orally every 6 to 8 hours for 7 to 10 days) is an appropriate alternative. If the allergy to penicillin is severe or if methicillin-resistant Staphylococcus aureus (MRSA) infection is suspected, either clindamycin (300 mg orally twice daily for 7 to 10 days) or trimethoprim-sulfamethoxazole double strength orally twice daily for 7 to 10 days should be used.

What are the principal microorganisms that cause puerperal mastitis?

Continue to the answer...

Staphylococci and Streptococcus viridans are the 2 dominant microorganisms that cause puerperal mastitis. For the initial treatment of mastitis, the drug of choice is dicloxacillin sodium (500 mg orally every 6 to 8 hours for 7 to 10 days). If the patient has a mild allergy to penicillin, cephalexin (500 mg orally every 6 to 8 hours for 7 to 10 days) is an appropriate alternative. If the allergy to penicillin is severe or if methicillin-resistant Staphylococcus aureus (MRSA) infection is suspected, either clindamycin (300 mg orally twice daily for 7 to 10 days) or trimethoprim-sulfamethoxazole double strength orally twice daily for 7 to 10 days should be used.

What are the principal microorganisms that cause puerperal mastitis?

Continue to the answer...

Staphylococci and Streptococcus viridans are the 2 dominant microorganisms that cause puerperal mastitis. For the initial treatment of mastitis, the drug of choice is dicloxacillin sodium (500 mg orally every 6 to 8 hours for 7 to 10 days). If the patient has a mild allergy to penicillin, cephalexin (500 mg orally every 6 to 8 hours for 7 to 10 days) is an appropriate alternative. If the allergy to penicillin is severe or if methicillin-resistant Staphylococcus aureus (MRSA) infection is suspected, either clindamycin (300 mg orally twice daily for 7 to 10 days) or trimethoprim-sulfamethoxazole double strength orally twice daily for 7 to 10 days should be used.

Younger, nonsmoking oral cancer patients have a higher risk of death than that of young smokers, and the outcomes may be related to immune deficiencies. The finding comes from a database of oral cavity squamous cell carcinoma (OSCC) patients treated between 1985 and 2015.

“Recent studies have shown an association between high neutrophil to lymphocyte ratio as a marker for poor outcome in several different cancers. This ratio is a surrogate marker for a patient’s immune function. A high ratio indicates an impaired immune function. This means that the ability for the immune system to identify and eradicate abnormal cells which have the potential to form cancer cells is impaired. We don’t know why this is occurring,” said Ian Ganly, MD, PhD, a head and neck surgeon with Memorial Sloan Kettering Cancer Center in New York.

Dr. Ganly is lead author of the new study, published online March 5 in Oral Oncology.

“Physicians should be aware these patients may have impaired immunity and may have a more aggressive presentation and clinical behavior. Such patients may require more comprehensive staging investigations for cancer and may require more comprehensive treatment. Following treatment these patients should also have a detailed and regular follow-up examination with appropriate imaging to detect early recurrence,” he said in an interview.

The research also suggests that immunotherapy may be effective in this group. “However, our findings are only preliminary and further research into this area is required before such therapy can be justified,” Dr. Ganly said.

The study comprised 2,073 patients overall (median age, 62; 43.5% female) and 100 younger nonsmoking patients (median age, 34; 56.0% female). After multivariate analysis, compared to young smokers, nonsmokers with OSCC had a greater risk of mortality (P = .0229), although they had a lower mortality risk than both smokers and nonsmokers over 40. After adjustments, young nonsmokers had a mortality resembling that of older patients, while mortality among young smokers was distinctly lower than that of older patients.

In a subset of 88 young nonsmoking patients, there was a higher neutrophil-to-lymphocyte ratio (median, 2.456) than that of similarly aged patients with thyroid cancer (median, 2.000; P = .0093) or salivary gland benign pathologies (median, 2.158; P = .0343).

The researchers are now studying the genomics of tumors found in smokers and nonsmokers and comparing them to tumors in older smokers and nonsmokers with OSCCs. They are performing a similar comparison of the immune environment of the tumors and patients’ immune system function. “For the genomics aspect I am looking to see if there are any unique alterations in the young nonsmokers that may explain the biology of these cancers. If so, there may be some alterations that can be targeted with new drugs. For the immune aspect, our goal is to see if there are any specific alterations in immune function unique to this population. Then it may be possible to deliver specific types of immunotherapy that focus in on these deficiencies,” said Dr. Ganly.

The study was funded by Fundación Alfonso Martín Escudero and the National Institutes of Health. Dr. Ganly has no relevant financial disclosures.

Younger, nonsmoking oral cancer patients have a higher risk of death than that of young smokers, and the outcomes may be related to immune deficiencies. The finding comes from a database of oral cavity squamous cell carcinoma (OSCC) patients treated between 1985 and 2015.

“Recent studies have shown an association between high neutrophil to lymphocyte ratio as a marker for poor outcome in several different cancers. This ratio is a surrogate marker for a patient’s immune function. A high ratio indicates an impaired immune function. This means that the ability for the immune system to identify and eradicate abnormal cells which have the potential to form cancer cells is impaired. We don’t know why this is occurring,” said Ian Ganly, MD, PhD, a head and neck surgeon with Memorial Sloan Kettering Cancer Center in New York.

Dr. Ganly is lead author of the new study, published online March 5 in Oral Oncology.

“Physicians should be aware these patients may have impaired immunity and may have a more aggressive presentation and clinical behavior. Such patients may require more comprehensive staging investigations for cancer and may require more comprehensive treatment. Following treatment these patients should also have a detailed and regular follow-up examination with appropriate imaging to detect early recurrence,” he said in an interview.

The research also suggests that immunotherapy may be effective in this group. “However, our findings are only preliminary and further research into this area is required before such therapy can be justified,” Dr. Ganly said.

The study comprised 2,073 patients overall (median age, 62; 43.5% female) and 100 younger nonsmoking patients (median age, 34; 56.0% female). After multivariate analysis, compared to young smokers, nonsmokers with OSCC had a greater risk of mortality (P = .0229), although they had a lower mortality risk than both smokers and nonsmokers over 40. After adjustments, young nonsmokers had a mortality resembling that of older patients, while mortality among young smokers was distinctly lower than that of older patients.

In a subset of 88 young nonsmoking patients, there was a higher neutrophil-to-lymphocyte ratio (median, 2.456) than that of similarly aged patients with thyroid cancer (median, 2.000; P = .0093) or salivary gland benign pathologies (median, 2.158; P = .0343).

The researchers are now studying the genomics of tumors found in smokers and nonsmokers and comparing them to tumors in older smokers and nonsmokers with OSCCs. They are performing a similar comparison of the immune environment of the tumors and patients’ immune system function. “For the genomics aspect I am looking to see if there are any unique alterations in the young nonsmokers that may explain the biology of these cancers. If so, there may be some alterations that can be targeted with new drugs. For the immune aspect, our goal is to see if there are any specific alterations in immune function unique to this population. Then it may be possible to deliver specific types of immunotherapy that focus in on these deficiencies,” said Dr. Ganly.

The study was funded by Fundación Alfonso Martín Escudero and the National Institutes of Health. Dr. Ganly has no relevant financial disclosures.

Younger, nonsmoking oral cancer patients have a higher risk of death than that of young smokers, and the outcomes may be related to immune deficiencies. The finding comes from a database of oral cavity squamous cell carcinoma (OSCC) patients treated between 1985 and 2015.

“Recent studies have shown an association between high neutrophil to lymphocyte ratio as a marker for poor outcome in several different cancers. This ratio is a surrogate marker for a patient’s immune function. A high ratio indicates an impaired immune function. This means that the ability for the immune system to identify and eradicate abnormal cells which have the potential to form cancer cells is impaired. We don’t know why this is occurring,” said Ian Ganly, MD, PhD, a head and neck surgeon with Memorial Sloan Kettering Cancer Center in New York.

Dr. Ganly is lead author of the new study, published online March 5 in Oral Oncology.

“Physicians should be aware these patients may have impaired immunity and may have a more aggressive presentation and clinical behavior. Such patients may require more comprehensive staging investigations for cancer and may require more comprehensive treatment. Following treatment these patients should also have a detailed and regular follow-up examination with appropriate imaging to detect early recurrence,” he said in an interview.

The research also suggests that immunotherapy may be effective in this group. “However, our findings are only preliminary and further research into this area is required before such therapy can be justified,” Dr. Ganly said.

The study comprised 2,073 patients overall (median age, 62; 43.5% female) and 100 younger nonsmoking patients (median age, 34; 56.0% female). After multivariate analysis, compared to young smokers, nonsmokers with OSCC had a greater risk of mortality (P = .0229), although they had a lower mortality risk than both smokers and nonsmokers over 40. After adjustments, young nonsmokers had a mortality resembling that of older patients, while mortality among young smokers was distinctly lower than that of older patients.

In a subset of 88 young nonsmoking patients, there was a higher neutrophil-to-lymphocyte ratio (median, 2.456) than that of similarly aged patients with thyroid cancer (median, 2.000; P = .0093) or salivary gland benign pathologies (median, 2.158; P = .0343).

The researchers are now studying the genomics of tumors found in smokers and nonsmokers and comparing them to tumors in older smokers and nonsmokers with OSCCs. They are performing a similar comparison of the immune environment of the tumors and patients’ immune system function. “For the genomics aspect I am looking to see if there are any unique alterations in the young nonsmokers that may explain the biology of these cancers. If so, there may be some alterations that can be targeted with new drugs. For the immune aspect, our goal is to see if there are any specific alterations in immune function unique to this population. Then it may be possible to deliver specific types of immunotherapy that focus in on these deficiencies,” said Dr. Ganly.

The study was funded by Fundación Alfonso Martín Escudero and the National Institutes of Health. Dr. Ganly has no relevant financial disclosures.

A congressional oversight subcommittee is investigating the Food and Drug Administration’s regulation of a high-risk heart pump, citing safety issues detailed by ProPublica.

The HeartWare Ventricular Assist Device, created to treat patients with severe heart failure, stopped meeting key federal standards as early as 2014. But the FDA took no decisive action even as those problems persisted, and thousands of Americans continued to be implanted with the pump.

By the end of 2020, the FDA had received more than 3,000 reports of deaths related to the HeartWare device, according to a ProPublica data analysis. A father of four died as his children tried to resuscitate him when his device suddenly stopped. A teenager died after vomiting blood in the middle of the night, while his mother struggled to restart a faulty pump.

“I am concerned by FDA’s slow action, over multiple administrations, to protect patients from this product despite early warning signs,” Rep. Raja Krishnamoorthi, D-Ill., said in a scathing letter sent March 22 to the agency’s commissioner, Robert Califf, MD.

Mr. Krishnamoorthi, the chairman of the U.S. House Committee on Oversight and Reform’s Subcommittee on Economic and Consumer Policy, requested information on how the FDA made regulatory decisions related to the HeartWare device and why it didn’t take further action.

The FDA did not provide comment to ProPublica on the subcommittee’s investigation and said it would respond directly to Mr. Krishnamoorthi. It also reiterated its response to ProPublica’s findings and said the agency had been closely overseeing the HeartWare device since 2012, with patient safety as its “highest priority.”

Medtronic, the company that acquired HeartWare in 2016, took the device off the market in June 2021. The company said that new data showed a competing heart pump had better outcomes. In response to the ProPublica investigation 2 months later, the company said it took the FDA’s inspections seriously and had worked closely with the agency to address issues with the device.

Medtronic declined to comment on the subcommittee’s investigation.

Mr. Krishnamoorthi asked in the letter if any steps were being taken to address how patients, doctors and other federal agencies are notified of problems that the FDA finds with medical devices.

Many patients told ProPublica they were never informed of issues with the HeartWare pump before or after their implants. Some people who still have the device said they weren’t told when it was taken off the market. Medtronic said in December it had confirmed 90% of U.S. patients had received notification of the HeartWare discontinuation, but that it was still working to reach the other 10%.

About 2,000 patients still had HeartWare pumps as of last year. The FDA and Medtronic recommended against removing those devices barring medical necessity because the surgery to do so carries a high risk.

In his letter, Mr. Krishnamoorthi gave the FDA a deadline of April 5 to respond.
 

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

A congressional oversight subcommittee is investigating the Food and Drug Administration’s regulation of a high-risk heart pump, citing safety issues detailed by ProPublica.

The HeartWare Ventricular Assist Device, created to treat patients with severe heart failure, stopped meeting key federal standards as early as 2014. But the FDA took no decisive action even as those problems persisted, and thousands of Americans continued to be implanted with the pump.

By the end of 2020, the FDA had received more than 3,000 reports of deaths related to the HeartWare device, according to a ProPublica data analysis. A father of four died as his children tried to resuscitate him when his device suddenly stopped. A teenager died after vomiting blood in the middle of the night, while his mother struggled to restart a faulty pump.

“I am concerned by FDA’s slow action, over multiple administrations, to protect patients from this product despite early warning signs,” Rep. Raja Krishnamoorthi, D-Ill., said in a scathing letter sent March 22 to the agency’s commissioner, Robert Califf, MD.

Mr. Krishnamoorthi, the chairman of the U.S. House Committee on Oversight and Reform’s Subcommittee on Economic and Consumer Policy, requested information on how the FDA made regulatory decisions related to the HeartWare device and why it didn’t take further action.

The FDA did not provide comment to ProPublica on the subcommittee’s investigation and said it would respond directly to Mr. Krishnamoorthi. It also reiterated its response to ProPublica’s findings and said the agency had been closely overseeing the HeartWare device since 2012, with patient safety as its “highest priority.”

Medtronic, the company that acquired HeartWare in 2016, took the device off the market in June 2021. The company said that new data showed a competing heart pump had better outcomes. In response to the ProPublica investigation 2 months later, the company said it took the FDA’s inspections seriously and had worked closely with the agency to address issues with the device.

Medtronic declined to comment on the subcommittee’s investigation.

Mr. Krishnamoorthi asked in the letter if any steps were being taken to address how patients, doctors and other federal agencies are notified of problems that the FDA finds with medical devices.

Many patients told ProPublica they were never informed of issues with the HeartWare pump before or after their implants. Some people who still have the device said they weren’t told when it was taken off the market. Medtronic said in December it had confirmed 90% of U.S. patients had received notification of the HeartWare discontinuation, but that it was still working to reach the other 10%.

About 2,000 patients still had HeartWare pumps as of last year. The FDA and Medtronic recommended against removing those devices barring medical necessity because the surgery to do so carries a high risk.

In his letter, Mr. Krishnamoorthi gave the FDA a deadline of April 5 to respond.
 

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

A congressional oversight subcommittee is investigating the Food and Drug Administration’s regulation of a high-risk heart pump, citing safety issues detailed by ProPublica.

The HeartWare Ventricular Assist Device, created to treat patients with severe heart failure, stopped meeting key federal standards as early as 2014. But the FDA took no decisive action even as those problems persisted, and thousands of Americans continued to be implanted with the pump.

By the end of 2020, the FDA had received more than 3,000 reports of deaths related to the HeartWare device, according to a ProPublica data analysis. A father of four died as his children tried to resuscitate him when his device suddenly stopped. A teenager died after vomiting blood in the middle of the night, while his mother struggled to restart a faulty pump.

“I am concerned by FDA’s slow action, over multiple administrations, to protect patients from this product despite early warning signs,” Rep. Raja Krishnamoorthi, D-Ill., said in a scathing letter sent March 22 to the agency’s commissioner, Robert Califf, MD.

Mr. Krishnamoorthi, the chairman of the U.S. House Committee on Oversight and Reform’s Subcommittee on Economic and Consumer Policy, requested information on how the FDA made regulatory decisions related to the HeartWare device and why it didn’t take further action.

The FDA did not provide comment to ProPublica on the subcommittee’s investigation and said it would respond directly to Mr. Krishnamoorthi. It also reiterated its response to ProPublica’s findings and said the agency had been closely overseeing the HeartWare device since 2012, with patient safety as its “highest priority.”

Medtronic, the company that acquired HeartWare in 2016, took the device off the market in June 2021. The company said that new data showed a competing heart pump had better outcomes. In response to the ProPublica investigation 2 months later, the company said it took the FDA’s inspections seriously and had worked closely with the agency to address issues with the device.

Medtronic declined to comment on the subcommittee’s investigation.

Mr. Krishnamoorthi asked in the letter if any steps were being taken to address how patients, doctors and other federal agencies are notified of problems that the FDA finds with medical devices.

Many patients told ProPublica they were never informed of issues with the HeartWare pump before or after their implants. Some people who still have the device said they weren’t told when it was taken off the market. Medtronic said in December it had confirmed 90% of U.S. patients had received notification of the HeartWare discontinuation, but that it was still working to reach the other 10%.

About 2,000 patients still had HeartWare pumps as of last year. The FDA and Medtronic recommended against removing those devices barring medical necessity because the surgery to do so carries a high risk.

In his letter, Mr. Krishnamoorthi gave the FDA a deadline of April 5 to respond.
 

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

A French research team has developed a microRNA (miRNA) signature for diagnosing endometriosis through a simple saliva test. Its validation in a larger cohort could soon allow doctors to have a cheap, noninvasive, and accurate tool to use in diagnosing a disease that, for the time being, is difficult to identify with any certainty. The researchers suggest that their methodology could be used as a blueprint to investigate other pathologies, both benign and malignant.

ENDO-miRNA study

miRNAs regulate as much as 60% of gene expression at the posttranscriptional level. In the setting of endometriosis, several authors have evaluated the relevance of a blood-based miRNA signature, but the results are discordant because of methodological and control group issues. Other researchers have also sought to develop a miRNA saliva test. A French team wanted to determine whether it was possible to define a saliva-based diagnostic miRNome signature that would allow patients with and without endometriosis to be differentiated and, from there, develop the first specific diagnostic test for the disease.

The prospective ENDO-miRNA study included saliva samples obtained from women with chronic pelvic pain suggestive of endometriosis. Exploratory procedures were performed to look for lesions. All the patients underwent either a laparoscopic procedure (therapeutic or diagnostic laparoscopy) and/or MRI imaging. For the patients who underwent laparoscopy, diagnosis was confirmed by histology. For the patients diagnosed with endometriosis without laparoscopic evaluation, all had MRI imaging with features of deep endometriosis.

One part of the study involved the identification of a biomarker based on genomewide miRNA expression profiling by small RNA sequencing using next-generation sequencing. The second part involved the development of a saliva-based miRNA diagnostic signature according to expression and accuracy profiling using a random forest algorithm.
 

High sensitivity, specificity

Among the 200 patients (mean age, 31 years) enrolled in the study, 76.5% (n = 153) were diagnosed with endometriosis. On average, their pain was statistically more severe than that of the women in the control group. The Visual Analogue Scale (VAS) scores were, respectively: dysmenorrhea 6 versus 5.0 (P < .001), dyspareunia 5.28 versus 4.95 (P < .001), and urinary pain during menstruation 4.35 versus 2.84 (P < .001).

Next-generation sequencing identified an average of 2,561 expressed miRNAs in the saliva samples. The feature selection method generated a subset of 109 miRNAs composing the endometriosis diagnostic signature. Among those miRNAs, 29 were associated with the main signaling pathways of endometriosis: PI3K/AKT, PTEN, Wnt/beta-catenin, HIF1-alpha/NF kappa B, and YAP/TAZ/EGFR.

The accuracy and reproducibility of the signature were tested on several data sets randomly composed of the same proportion of controls and patients with endometriosis. The respective sensitivity, specificity, and area under the curve for the diagnostic miRNA signature were 96.7%, 100%, and 98.3%, respectively.

The study’s results support the use of a saliva-based miRNA signature for diagnosing whether a patient is discordant/complex (chronic pelvic pain suggestive of endometriosis and both negative clinical examination and imaging findings) or has early-stage or advanced-stage endometriosis.

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

A French research team has developed a microRNA (miRNA) signature for diagnosing endometriosis through a simple saliva test. Its validation in a larger cohort could soon allow doctors to have a cheap, noninvasive, and accurate tool to use in diagnosing a disease that, for the time being, is difficult to identify with any certainty. The researchers suggest that their methodology could be used as a blueprint to investigate other pathologies, both benign and malignant.

ENDO-miRNA study

miRNAs regulate as much as 60% of gene expression at the posttranscriptional level. In the setting of endometriosis, several authors have evaluated the relevance of a blood-based miRNA signature, but the results are discordant because of methodological and control group issues. Other researchers have also sought to develop a miRNA saliva test. A French team wanted to determine whether it was possible to define a saliva-based diagnostic miRNome signature that would allow patients with and without endometriosis to be differentiated and, from there, develop the first specific diagnostic test for the disease.

The prospective ENDO-miRNA study included saliva samples obtained from women with chronic pelvic pain suggestive of endometriosis. Exploratory procedures were performed to look for lesions. All the patients underwent either a laparoscopic procedure (therapeutic or diagnostic laparoscopy) and/or MRI imaging. For the patients who underwent laparoscopy, diagnosis was confirmed by histology. For the patients diagnosed with endometriosis without laparoscopic evaluation, all had MRI imaging with features of deep endometriosis.

One part of the study involved the identification of a biomarker based on genomewide miRNA expression profiling by small RNA sequencing using next-generation sequencing. The second part involved the development of a saliva-based miRNA diagnostic signature according to expression and accuracy profiling using a random forest algorithm.
 

High sensitivity, specificity

Among the 200 patients (mean age, 31 years) enrolled in the study, 76.5% (n = 153) were diagnosed with endometriosis. On average, their pain was statistically more severe than that of the women in the control group. The Visual Analogue Scale (VAS) scores were, respectively: dysmenorrhea 6 versus 5.0 (P < .001), dyspareunia 5.28 versus 4.95 (P < .001), and urinary pain during menstruation 4.35 versus 2.84 (P < .001).

Next-generation sequencing identified an average of 2,561 expressed miRNAs in the saliva samples. The feature selection method generated a subset of 109 miRNAs composing the endometriosis diagnostic signature. Among those miRNAs, 29 were associated with the main signaling pathways of endometriosis: PI3K/AKT, PTEN, Wnt/beta-catenin, HIF1-alpha/NF kappa B, and YAP/TAZ/EGFR.

The accuracy and reproducibility of the signature were tested on several data sets randomly composed of the same proportion of controls and patients with endometriosis. The respective sensitivity, specificity, and area under the curve for the diagnostic miRNA signature were 96.7%, 100%, and 98.3%, respectively.

The study’s results support the use of a saliva-based miRNA signature for diagnosing whether a patient is discordant/complex (chronic pelvic pain suggestive of endometriosis and both negative clinical examination and imaging findings) or has early-stage or advanced-stage endometriosis.

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

A French research team has developed a microRNA (miRNA) signature for diagnosing endometriosis through a simple saliva test. Its validation in a larger cohort could soon allow doctors to have a cheap, noninvasive, and accurate tool to use in diagnosing a disease that, for the time being, is difficult to identify with any certainty. The researchers suggest that their methodology could be used as a blueprint to investigate other pathologies, both benign and malignant.

ENDO-miRNA study

miRNAs regulate as much as 60% of gene expression at the posttranscriptional level. In the setting of endometriosis, several authors have evaluated the relevance of a blood-based miRNA signature, but the results are discordant because of methodological and control group issues. Other researchers have also sought to develop a miRNA saliva test. A French team wanted to determine whether it was possible to define a saliva-based diagnostic miRNome signature that would allow patients with and without endometriosis to be differentiated and, from there, develop the first specific diagnostic test for the disease.

The prospective ENDO-miRNA study included saliva samples obtained from women with chronic pelvic pain suggestive of endometriosis. Exploratory procedures were performed to look for lesions. All the patients underwent either a laparoscopic procedure (therapeutic or diagnostic laparoscopy) and/or MRI imaging. For the patients who underwent laparoscopy, diagnosis was confirmed by histology. For the patients diagnosed with endometriosis without laparoscopic evaluation, all had MRI imaging with features of deep endometriosis.

One part of the study involved the identification of a biomarker based on genomewide miRNA expression profiling by small RNA sequencing using next-generation sequencing. The second part involved the development of a saliva-based miRNA diagnostic signature according to expression and accuracy profiling using a random forest algorithm.
 

High sensitivity, specificity

Among the 200 patients (mean age, 31 years) enrolled in the study, 76.5% (n = 153) were diagnosed with endometriosis. On average, their pain was statistically more severe than that of the women in the control group. The Visual Analogue Scale (VAS) scores were, respectively: dysmenorrhea 6 versus 5.0 (P < .001), dyspareunia 5.28 versus 4.95 (P < .001), and urinary pain during menstruation 4.35 versus 2.84 (P < .001).

Next-generation sequencing identified an average of 2,561 expressed miRNAs in the saliva samples. The feature selection method generated a subset of 109 miRNAs composing the endometriosis diagnostic signature. Among those miRNAs, 29 were associated with the main signaling pathways of endometriosis: PI3K/AKT, PTEN, Wnt/beta-catenin, HIF1-alpha/NF kappa B, and YAP/TAZ/EGFR.

The accuracy and reproducibility of the signature were tested on several data sets randomly composed of the same proportion of controls and patients with endometriosis. The respective sensitivity, specificity, and area under the curve for the diagnostic miRNA signature were 96.7%, 100%, and 98.3%, respectively.

The study’s results support the use of a saliva-based miRNA signature for diagnosing whether a patient is discordant/complex (chronic pelvic pain suggestive of endometriosis and both negative clinical examination and imaging findings) or has early-stage or advanced-stage endometriosis.

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

A small, and likely decreasing, number of health care providers in the United States perform abortions, and there is a risk that the count will be shrinking in the face of legislative attacks on the service, researchers have found.

Until now, producing an accurate count of abortion service providers in the United States has been difficult, leaving researchers to rely on indirect assessments of abortion clinics rather than counts of physicians who perform the procedure.

But the authors of a research letter published in JAMA Internal Medicine have come up with a number: Roughly 3,550 clinicians provide procedural and medication abortions, while 22,001 manage pregnancy loss with the same procedures and medications. More than half of all abortions in the United States now are achieved by medication.

The small number of providers is a cause for concern as a growing number of states move to restrict access to abortions, experts say.

“Abortions are only available if clinicians provide them,” said Julia Strasser, DrPH, MPH, senior research scientist at the George Washington University Milken Institute School of Public Health, Washington, D.C., who led the research. “This study finds that a variety of clinician types provide abortion care. But the number of abortion providers is low, and increasing restrictions will only make this worse.”

For their census, Dr. Strasser and her colleagues evaluated medical claims covering a full year from a private data company. They focused on two sets of services: medications (misoprostol and mifepristone) used in abortion care and pregnancy loss and procedures such as dilation and curettage and dilation and evacuation. Services were categorized as induced abortion or management by pregnancy loss on the basis of medical coding.

The researchers found that there were 3,550 abortion providers and 22,001 clinicians who managed pregnancy loss. Of those who induced abortions, 88% were physicians and 12% were advanced practice clinicians.

The clinicians who most frequently provided induced abortions were ob/gyns (72%), followed by family physicians (9%), advanced practice registered nurses (8%), and nurse midwives (3%). Several other specialists performed about 1% of abortions each.

Dr. Strasser said that 3,550 is an undercount because many providers do offer abortions but cannot or do not bill for them. Even so, the number likely will fall because fewer medical students are being trained for abortion procedures, according to Kaiser Health News.

Despite recommendations from the American College of Obstetricians and Gynecologists for standardized training on abortion care during medical residency, the number of programs that prohibit that training has surged in recent years, the report notes.
 

Restrictions looming

Compounding the problem, the researchers say, is the recent spate of state-level legislation regarding access to abortion. The U.S. Supreme Court is due to rule soon on a Mississippi law banning all abortions over 15 weeks’ gestational age, except in medical emergencies and in the case of severe fetal abnormalities.

Last May, Texas passed a law outlawing termination of pregnancy after 6 weeks of gestation – before many women know they’re pregnant. The law created a bounty system that permits essentially anyone in the United States to sue a woman in the state who seeks an abortion outside the law or anyone who assists her – including health care professionals. The Supreme Court in December refused to overturn the law – which reportedly has triggered a surge in women seeking abortion services in neighboring Oklahoma.

The legal environment is greatly increasing the risk that more clinicians will drop out of the workforce, Dr. Strasser told this news organization.

“As this happens, abortion care will undoubtedly become harder to access, especially for vulnerable populations,” she said. “Patients will have to travel farther, pay more money, or forgo necessary care.”

Another major variable is insurance coverage, the researchers found. Abortion coverage is highly restricted under private insurance and Medicaid, they note. Beyond increasingly restrictive payment issues, policies seen as punitive toward clinicians may cause many to stop offering medication and procedural services, Dr. Strasser said.

“The national political climate will likely see more barriers and less access to care in the coming months and years,” she told this news organization. “However, some states are taking concrete steps to protect abortion access for their residents and for others out of state. In supportive environments like these, enhanced training, expanded scope of practice, and improved reimbursement policies can increase access.”

If the Supreme Court overturns Roe v. Wade, Kaiser Health News reported, 26 states would likely ban abortion, triggering a flood of patients to states where the procedure remains more widely available.

According to the Center for Reproductive Rights, states that have expanded access are Washington, Oregon, California, New York, Vermont, Connecticut, and New Jersey. Another 12 states offer protected access, in which abortion is likely to remain legal even if Roe v. Wade is overturned, since in many of them, abortion is protected under their state constitutions.
 

Pivot to telehealth?

Another study, published in the same issue of JAMA Internal Medicine, evaluated health outcomes for 3,779 women. That study found that eligibility screening for medical abortions by history alone, without pelvic examination or ultrasonography, was safe and effective. That study found that medications were either dispensed in person or through the mail.

Taken together, the two studies suggest that more abortion services may shift toward telehealth, which could expand the number of health care professionals performing such services. Providers could include nurse practitioners, midwives, and physician assistants, said Melissa Grant, chief operating officer of carafem, a reproductive health and abortion service provider.

The service, which has offices in Atlanta, Chicago, Nashville, and Washington, D.C., has found that many patients prefer online appointments, especially if they live in rural areas, Ms. Grant said. The pandemic created a push toward online services.

“Even before the current breadth of restrictive legislation, we were seeing in increase because of COVID,” she said. “Most likely, abortion providers will continue to be pushed out of the profession, so having an option that’s widely available no matter where you live is essential. The United States is moving toward a system where the ZIP code you live in will foretell what care you get. That’s chilling.”

Those who currently provide abortion care have two advantages over what was available previously, Ms. Grant said. First, medical abortion is much more common, and data show that it is safe and effective for most pregnant people, as long as they undergo a health screening. Second, the boom in telehealth during the pandemic means providers are much more experienced in this type of service than before.

As more services such as carafem crop up, costs will drop, since a telehealth clinic – even one that uses health care professionals – has fewer expenses, such as for rent and equipment, than a physical facility.

“Because of the stigma around abortion, this is not likely to prompt a big rush of start-ups, but I do think we’re going to see a shake-up in the way services are being offered, and both patients and providers will likely turn toward technology,” Ms. Grant said. “An environment like this will require flexibility, innovation, and some real grit. We may take some time to get there, but it’s possible this moment is a pivot point in how abortion care is provided.”

Some of the researchers received grants from the Susan T. Buffett Foundation.

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

A small, and likely decreasing, number of health care providers in the United States perform abortions, and there is a risk that the count will be shrinking in the face of legislative attacks on the service, researchers have found.

Until now, producing an accurate count of abortion service providers in the United States has been difficult, leaving researchers to rely on indirect assessments of abortion clinics rather than counts of physicians who perform the procedure.

But the authors of a research letter published in JAMA Internal Medicine have come up with a number: Roughly 3,550 clinicians provide procedural and medication abortions, while 22,001 manage pregnancy loss with the same procedures and medications. More than half of all abortions in the United States now are achieved by medication.

The small number of providers is a cause for concern as a growing number of states move to restrict access to abortions, experts say.

“Abortions are only available if clinicians provide them,” said Julia Strasser, DrPH, MPH, senior research scientist at the George Washington University Milken Institute School of Public Health, Washington, D.C., who led the research. “This study finds that a variety of clinician types provide abortion care. But the number of abortion providers is low, and increasing restrictions will only make this worse.”

For their census, Dr. Strasser and her colleagues evaluated medical claims covering a full year from a private data company. They focused on two sets of services: medications (misoprostol and mifepristone) used in abortion care and pregnancy loss and procedures such as dilation and curettage and dilation and evacuation. Services were categorized as induced abortion or management by pregnancy loss on the basis of medical coding.

The researchers found that there were 3,550 abortion providers and 22,001 clinicians who managed pregnancy loss. Of those who induced abortions, 88% were physicians and 12% were advanced practice clinicians.

The clinicians who most frequently provided induced abortions were ob/gyns (72%), followed by family physicians (9%), advanced practice registered nurses (8%), and nurse midwives (3%). Several other specialists performed about 1% of abortions each.

Dr. Strasser said that 3,550 is an undercount because many providers do offer abortions but cannot or do not bill for them. Even so, the number likely will fall because fewer medical students are being trained for abortion procedures, according to Kaiser Health News.

Despite recommendations from the American College of Obstetricians and Gynecologists for standardized training on abortion care during medical residency, the number of programs that prohibit that training has surged in recent years, the report notes.
 

Restrictions looming

Compounding the problem, the researchers say, is the recent spate of state-level legislation regarding access to abortion. The U.S. Supreme Court is due to rule soon on a Mississippi law banning all abortions over 15 weeks’ gestational age, except in medical emergencies and in the case of severe fetal abnormalities.

Last May, Texas passed a law outlawing termination of pregnancy after 6 weeks of gestation – before many women know they’re pregnant. The law created a bounty system that permits essentially anyone in the United States to sue a woman in the state who seeks an abortion outside the law or anyone who assists her – including health care professionals. The Supreme Court in December refused to overturn the law – which reportedly has triggered a surge in women seeking abortion services in neighboring Oklahoma.

The legal environment is greatly increasing the risk that more clinicians will drop out of the workforce, Dr. Strasser told this news organization.

“As this happens, abortion care will undoubtedly become harder to access, especially for vulnerable populations,” she said. “Patients will have to travel farther, pay more money, or forgo necessary care.”

Another major variable is insurance coverage, the researchers found. Abortion coverage is highly restricted under private insurance and Medicaid, they note. Beyond increasingly restrictive payment issues, policies seen as punitive toward clinicians may cause many to stop offering medication and procedural services, Dr. Strasser said.

“The national political climate will likely see more barriers and less access to care in the coming months and years,” she told this news organization. “However, some states are taking concrete steps to protect abortion access for their residents and for others out of state. In supportive environments like these, enhanced training, expanded scope of practice, and improved reimbursement policies can increase access.”

If the Supreme Court overturns Roe v. Wade, Kaiser Health News reported, 26 states would likely ban abortion, triggering a flood of patients to states where the procedure remains more widely available.

According to the Center for Reproductive Rights, states that have expanded access are Washington, Oregon, California, New York, Vermont, Connecticut, and New Jersey. Another 12 states offer protected access, in which abortion is likely to remain legal even if Roe v. Wade is overturned, since in many of them, abortion is protected under their state constitutions.
 

Pivot to telehealth?

Another study, published in the same issue of JAMA Internal Medicine, evaluated health outcomes for 3,779 women. That study found that eligibility screening for medical abortions by history alone, without pelvic examination or ultrasonography, was safe and effective. That study found that medications were either dispensed in person or through the mail.

Taken together, the two studies suggest that more abortion services may shift toward telehealth, which could expand the number of health care professionals performing such services. Providers could include nurse practitioners, midwives, and physician assistants, said Melissa Grant, chief operating officer of carafem, a reproductive health and abortion service provider.

The service, which has offices in Atlanta, Chicago, Nashville, and Washington, D.C., has found that many patients prefer online appointments, especially if they live in rural areas, Ms. Grant said. The pandemic created a push toward online services.

“Even before the current breadth of restrictive legislation, we were seeing in increase because of COVID,” she said. “Most likely, abortion providers will continue to be pushed out of the profession, so having an option that’s widely available no matter where you live is essential. The United States is moving toward a system where the ZIP code you live in will foretell what care you get. That’s chilling.”

Those who currently provide abortion care have two advantages over what was available previously, Ms. Grant said. First, medical abortion is much more common, and data show that it is safe and effective for most pregnant people, as long as they undergo a health screening. Second, the boom in telehealth during the pandemic means providers are much more experienced in this type of service than before.

As more services such as carafem crop up, costs will drop, since a telehealth clinic – even one that uses health care professionals – has fewer expenses, such as for rent and equipment, than a physical facility.

“Because of the stigma around abortion, this is not likely to prompt a big rush of start-ups, but I do think we’re going to see a shake-up in the way services are being offered, and both patients and providers will likely turn toward technology,” Ms. Grant said. “An environment like this will require flexibility, innovation, and some real grit. We may take some time to get there, but it’s possible this moment is a pivot point in how abortion care is provided.”

Some of the researchers received grants from the Susan T. Buffett Foundation.

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

A small, and likely decreasing, number of health care providers in the United States perform abortions, and there is a risk that the count will be shrinking in the face of legislative attacks on the service, researchers have found.

Until now, producing an accurate count of abortion service providers in the United States has been difficult, leaving researchers to rely on indirect assessments of abortion clinics rather than counts of physicians who perform the procedure.

But the authors of a research letter published in JAMA Internal Medicine have come up with a number: Roughly 3,550 clinicians provide procedural and medication abortions, while 22,001 manage pregnancy loss with the same procedures and medications. More than half of all abortions in the United States now are achieved by medication.

The small number of providers is a cause for concern as a growing number of states move to restrict access to abortions, experts say.

“Abortions are only available if clinicians provide them,” said Julia Strasser, DrPH, MPH, senior research scientist at the George Washington University Milken Institute School of Public Health, Washington, D.C., who led the research. “This study finds that a variety of clinician types provide abortion care. But the number of abortion providers is low, and increasing restrictions will only make this worse.”

For their census, Dr. Strasser and her colleagues evaluated medical claims covering a full year from a private data company. They focused on two sets of services: medications (misoprostol and mifepristone) used in abortion care and pregnancy loss and procedures such as dilation and curettage and dilation and evacuation. Services were categorized as induced abortion or management by pregnancy loss on the basis of medical coding.

The researchers found that there were 3,550 abortion providers and 22,001 clinicians who managed pregnancy loss. Of those who induced abortions, 88% were physicians and 12% were advanced practice clinicians.

The clinicians who most frequently provided induced abortions were ob/gyns (72%), followed by family physicians (9%), advanced practice registered nurses (8%), and nurse midwives (3%). Several other specialists performed about 1% of abortions each.

Dr. Strasser said that 3,550 is an undercount because many providers do offer abortions but cannot or do not bill for them. Even so, the number likely will fall because fewer medical students are being trained for abortion procedures, according to Kaiser Health News.

Despite recommendations from the American College of Obstetricians and Gynecologists for standardized training on abortion care during medical residency, the number of programs that prohibit that training has surged in recent years, the report notes.
 

Restrictions looming

Compounding the problem, the researchers say, is the recent spate of state-level legislation regarding access to abortion. The U.S. Supreme Court is due to rule soon on a Mississippi law banning all abortions over 15 weeks’ gestational age, except in medical emergencies and in the case of severe fetal abnormalities.

Last May, Texas passed a law outlawing termination of pregnancy after 6 weeks of gestation – before many women know they’re pregnant. The law created a bounty system that permits essentially anyone in the United States to sue a woman in the state who seeks an abortion outside the law or anyone who assists her – including health care professionals. The Supreme Court in December refused to overturn the law – which reportedly has triggered a surge in women seeking abortion services in neighboring Oklahoma.

The legal environment is greatly increasing the risk that more clinicians will drop out of the workforce, Dr. Strasser told this news organization.

“As this happens, abortion care will undoubtedly become harder to access, especially for vulnerable populations,” she said. “Patients will have to travel farther, pay more money, or forgo necessary care.”

Another major variable is insurance coverage, the researchers found. Abortion coverage is highly restricted under private insurance and Medicaid, they note. Beyond increasingly restrictive payment issues, policies seen as punitive toward clinicians may cause many to stop offering medication and procedural services, Dr. Strasser said.

“The national political climate will likely see more barriers and less access to care in the coming months and years,” she told this news organization. “However, some states are taking concrete steps to protect abortion access for their residents and for others out of state. In supportive environments like these, enhanced training, expanded scope of practice, and improved reimbursement policies can increase access.”

If the Supreme Court overturns Roe v. Wade, Kaiser Health News reported, 26 states would likely ban abortion, triggering a flood of patients to states where the procedure remains more widely available.

According to the Center for Reproductive Rights, states that have expanded access are Washington, Oregon, California, New York, Vermont, Connecticut, and New Jersey. Another 12 states offer protected access, in which abortion is likely to remain legal even if Roe v. Wade is overturned, since in many of them, abortion is protected under their state constitutions.
 

Pivot to telehealth?

Another study, published in the same issue of JAMA Internal Medicine, evaluated health outcomes for 3,779 women. That study found that eligibility screening for medical abortions by history alone, without pelvic examination or ultrasonography, was safe and effective. That study found that medications were either dispensed in person or through the mail.

Taken together, the two studies suggest that more abortion services may shift toward telehealth, which could expand the number of health care professionals performing such services. Providers could include nurse practitioners, midwives, and physician assistants, said Melissa Grant, chief operating officer of carafem, a reproductive health and abortion service provider.

The service, which has offices in Atlanta, Chicago, Nashville, and Washington, D.C., has found that many patients prefer online appointments, especially if they live in rural areas, Ms. Grant said. The pandemic created a push toward online services.

“Even before the current breadth of restrictive legislation, we were seeing in increase because of COVID,” she said. “Most likely, abortion providers will continue to be pushed out of the profession, so having an option that’s widely available no matter where you live is essential. The United States is moving toward a system where the ZIP code you live in will foretell what care you get. That’s chilling.”

Those who currently provide abortion care have two advantages over what was available previously, Ms. Grant said. First, medical abortion is much more common, and data show that it is safe and effective for most pregnant people, as long as they undergo a health screening. Second, the boom in telehealth during the pandemic means providers are much more experienced in this type of service than before.

As more services such as carafem crop up, costs will drop, since a telehealth clinic – even one that uses health care professionals – has fewer expenses, such as for rent and equipment, than a physical facility.

“Because of the stigma around abortion, this is not likely to prompt a big rush of start-ups, but I do think we’re going to see a shake-up in the way services are being offered, and both patients and providers will likely turn toward technology,” Ms. Grant said. “An environment like this will require flexibility, innovation, and some real grit. We may take some time to get there, but it’s possible this moment is a pivot point in how abortion care is provided.”

Some of the researchers received grants from the Susan T. Buffett Foundation.

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

The past several weeks have been rather tumultuous for LGBTQ Americans, particularly transgender youth. The Texas attorney general penned a legal opinion stating that hormone therapy and puberty blockers for transgender youth constitute “child abuse” under Texas law. Following the statement, Texas governor Greg Abbott swiftly issued a directive to protective services to launch investigations into families providing such services to their children. Almost simultaneously, the Florida Senate approved the Parental Rights in Education bill (dubbed the “Don’t Say Gay” bill by opponents), which limits how sexual orientation and gender identity are taught in the classroom.

Despite the benefits of gender-affirming care for gender-diverse youth, 22 states have introduced legislation that bans the provision of gender-affirming medical care under the age of 18, even with the consent of parents or legal guardians.¹ Unfortunately, gender-diverse youth are more likely than are their cisgender peers to experience poverty, homelessness, depression, suicide, and violence.¹ As a result of ongoing stigma, many gender-diverse patients are hesitant to seek out professional medical care, which includes mental health care, routine health care, and gender-affirming therapies. The positive effects of gender-affirming care for transgender youth are clear, and life saving for many. Gender-affirming medical interventions improve social and mental health outcomes, such as decreased suicidal ideation, depression, and improved peer relations that last until adulthood.¹

As with all aspects in medicine, providers and families of gender-diverse youth need to balance the four ethical principles that guide decision-making and informed consent. For practitioners working with the pediatric/adolescent populations, the age at which pediatric or adolescent patients can truly provide consent or assent is still not determined.² This presents a unique set of challenges in the realm of gender-affirming care particularly when children/adolescents and their parents have differing perspectives on proposed treatment plans. For example, when discussing fertility preservation, a 16-year-old patient is much more likely to understand implications of future fertility than a 9-year-old patient. Furthermore, providers must find the delicate balance between maximizing treatment benefits (beneficence) while minimizing harm (nonmaleficence), while also discussing the uncertainty about the long-term risks of gender-affirming treatments.² The final obligation for health care providers is ensuring all patients have equitable access to care (justice) – which is why we must all oppose legislation that criminalizes treatment for gender-diverse youth, regardless of our individual opinions on gender-affirming care for patients.

Opponents of gender-affirming care for transgender youth often cite concern about permanent effects or psychological distress if a child begins gender-affirming therapy and then chooses to discontinue. While the medical community should be, and is alarmed about patients who detransition, the solution to limiting the number of patients who experience regret or detransition is most certainly not criminalizing or universally banning gender-affirming care for all patients.³ Experts in transgender medicine and surgery (some of whom are transgender themselves) have expressed apprehension regarding the evaluation of gender-diverse children and youth. The concern is not whether gender-diverse youth should receive gender-affirming treatments, but rather they questioned the assessments made by providers who may be less fully qualified to deliver treatment and who deviate from well-established standards of care.⁴ The logical solution would be to further improve upon the current standards of care, ensure providers have appropriate training, and to expand multidisciplinary models of gender-affirming centers for youth.

If politicians were truly worried about the welfare of gender-diverse children, there would be a shift in the allocation of funds or resources to improve research endeavors and establish effective multidisciplinary clinics to meet the needs of this marginalized patient population. While the medical community should carefully examine gender-affirming care in transgender youth, criminalizing care is unconscionable. Our community needs more evidence-based research, providers, and centers, not politics.

The LGBTQ community and providers are rightfully fearful of the repercussions of such legislation. And the politicians and supporters of such bills should be equally apprehensive of the negative consequences this legislation will have on the mental health of transgender youth.

While the model for gender-affirming medicine and surgery needs continual assessment to ensure all patients, regardless of age and goals of transition, are receiving evidence-based, quality care, these discussions and subsequent decision-making should occur among medical professionals, not among politicians and the lay press.⁴

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

References

1. Hughes LD et al. ‘These laws will be devastating’: Provider perspectives on legislation banning gender-affirming care for transgender adolescents. J Adol Health;2021;69:976-82.

2. Kimberly LL et al. Ethical issues in gender-affirming care for youth. Pediatrics. Pediatrics;018;142(6)e20181537.

3. Ashley F. Psychol Sexual Orient Gender Divers. APA PsycNet. 2021.

4. Ault A. Transgender docs warn about gender-affirmative care for youth. WebMD. 2021 Nov. Accessed March 14, 2022.

The past several weeks have been rather tumultuous for LGBTQ Americans, particularly transgender youth. The Texas attorney general penned a legal opinion stating that hormone therapy and puberty blockers for transgender youth constitute “child abuse” under Texas law. Following the statement, Texas governor Greg Abbott swiftly issued a directive to protective services to launch investigations into families providing such services to their children. Almost simultaneously, the Florida Senate approved the Parental Rights in Education bill (dubbed the “Don’t Say Gay” bill by opponents), which limits how sexual orientation and gender identity are taught in the classroom.

Despite the benefits of gender-affirming care for gender-diverse youth, 22 states have introduced legislation that bans the provision of gender-affirming medical care under the age of 18, even with the consent of parents or legal guardians.¹ Unfortunately, gender-diverse youth are more likely than are their cisgender peers to experience poverty, homelessness, depression, suicide, and violence.¹ As a result of ongoing stigma, many gender-diverse patients are hesitant to seek out professional medical care, which includes mental health care, routine health care, and gender-affirming therapies. The positive effects of gender-affirming care for transgender youth are clear, and life saving for many. Gender-affirming medical interventions improve social and mental health outcomes, such as decreased suicidal ideation, depression, and improved peer relations that last until adulthood.¹

As with all aspects in medicine, providers and families of gender-diverse youth need to balance the four ethical principles that guide decision-making and informed consent. For practitioners working with the pediatric/adolescent populations, the age at which pediatric or adolescent patients can truly provide consent or assent is still not determined.² This presents a unique set of challenges in the realm of gender-affirming care particularly when children/adolescents and their parents have differing perspectives on proposed treatment plans. For example, when discussing fertility preservation, a 16-year-old patient is much more likely to understand implications of future fertility than a 9-year-old patient. Furthermore, providers must find the delicate balance between maximizing treatment benefits (beneficence) while minimizing harm (nonmaleficence), while also discussing the uncertainty about the long-term risks of gender-affirming treatments.² The final obligation for health care providers is ensuring all patients have equitable access to care (justice) – which is why we must all oppose legislation that criminalizes treatment for gender-diverse youth, regardless of our individual opinions on gender-affirming care for patients.

Opponents of gender-affirming care for transgender youth often cite concern about permanent effects or psychological distress if a child begins gender-affirming therapy and then chooses to discontinue. While the medical community should be, and is alarmed about patients who detransition, the solution to limiting the number of patients who experience regret or detransition is most certainly not criminalizing or universally banning gender-affirming care for all patients.³ Experts in transgender medicine and surgery (some of whom are transgender themselves) have expressed apprehension regarding the evaluation of gender-diverse children and youth. The concern is not whether gender-diverse youth should receive gender-affirming treatments, but rather they questioned the assessments made by providers who may be less fully qualified to deliver treatment and who deviate from well-established standards of care.⁴ The logical solution would be to further improve upon the current standards of care, ensure providers have appropriate training, and to expand multidisciplinary models of gender-affirming centers for youth.

If politicians were truly worried about the welfare of gender-diverse children, there would be a shift in the allocation of funds or resources to improve research endeavors and establish effective multidisciplinary clinics to meet the needs of this marginalized patient population. While the medical community should carefully examine gender-affirming care in transgender youth, criminalizing care is unconscionable. Our community needs more evidence-based research, providers, and centers, not politics.

The LGBTQ community and providers are rightfully fearful of the repercussions of such legislation. And the politicians and supporters of such bills should be equally apprehensive of the negative consequences this legislation will have on the mental health of transgender youth.

While the model for gender-affirming medicine and surgery needs continual assessment to ensure all patients, regardless of age and goals of transition, are receiving evidence-based, quality care, these discussions and subsequent decision-making should occur among medical professionals, not among politicians and the lay press.⁴

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

References

1. Hughes LD et al. ‘These laws will be devastating’: Provider perspectives on legislation banning gender-affirming care for transgender adolescents. J Adol Health;2021;69:976-82.

2. Kimberly LL et al. Ethical issues in gender-affirming care for youth. Pediatrics. Pediatrics;018;142(6)e20181537.

3. Ashley F. Psychol Sexual Orient Gender Divers. APA PsycNet. 2021.

4. Ault A. Transgender docs warn about gender-affirmative care for youth. WebMD. 2021 Nov. Accessed March 14, 2022.

The past several weeks have been rather tumultuous for LGBTQ Americans, particularly transgender youth. The Texas attorney general penned a legal opinion stating that hormone therapy and puberty blockers for transgender youth constitute “child abuse” under Texas law. Following the statement, Texas governor Greg Abbott swiftly issued a directive to protective services to launch investigations into families providing such services to their children. Almost simultaneously, the Florida Senate approved the Parental Rights in Education bill (dubbed the “Don’t Say Gay” bill by opponents), which limits how sexual orientation and gender identity are taught in the classroom.

Despite the benefits of gender-affirming care for gender-diverse youth, 22 states have introduced legislation that bans the provision of gender-affirming medical care under the age of 18, even with the consent of parents or legal guardians.¹ Unfortunately, gender-diverse youth are more likely than are their cisgender peers to experience poverty, homelessness, depression, suicide, and violence.¹ As a result of ongoing stigma, many gender-diverse patients are hesitant to seek out professional medical care, which includes mental health care, routine health care, and gender-affirming therapies. The positive effects of gender-affirming care for transgender youth are clear, and life saving for many. Gender-affirming medical interventions improve social and mental health outcomes, such as decreased suicidal ideation, depression, and improved peer relations that last until adulthood.¹

As with all aspects in medicine, providers and families of gender-diverse youth need to balance the four ethical principles that guide decision-making and informed consent. For practitioners working with the pediatric/adolescent populations, the age at which pediatric or adolescent patients can truly provide consent or assent is still not determined.² This presents a unique set of challenges in the realm of gender-affirming care particularly when children/adolescents and their parents have differing perspectives on proposed treatment plans. For example, when discussing fertility preservation, a 16-year-old patient is much more likely to understand implications of future fertility than a 9-year-old patient. Furthermore, providers must find the delicate balance between maximizing treatment benefits (beneficence) while minimizing harm (nonmaleficence), while also discussing the uncertainty about the long-term risks of gender-affirming treatments.² The final obligation for health care providers is ensuring all patients have equitable access to care (justice) – which is why we must all oppose legislation that criminalizes treatment for gender-diverse youth, regardless of our individual opinions on gender-affirming care for patients.

Opponents of gender-affirming care for transgender youth often cite concern about permanent effects or psychological distress if a child begins gender-affirming therapy and then chooses to discontinue. While the medical community should be, and is alarmed about patients who detransition, the solution to limiting the number of patients who experience regret or detransition is most certainly not criminalizing or universally banning gender-affirming care for all patients.³ Experts in transgender medicine and surgery (some of whom are transgender themselves) have expressed apprehension regarding the evaluation of gender-diverse children and youth. The concern is not whether gender-diverse youth should receive gender-affirming treatments, but rather they questioned the assessments made by providers who may be less fully qualified to deliver treatment and who deviate from well-established standards of care.⁴ The logical solution would be to further improve upon the current standards of care, ensure providers have appropriate training, and to expand multidisciplinary models of gender-affirming centers for youth.

If politicians were truly worried about the welfare of gender-diverse children, there would be a shift in the allocation of funds or resources to improve research endeavors and establish effective multidisciplinary clinics to meet the needs of this marginalized patient population. While the medical community should carefully examine gender-affirming care in transgender youth, criminalizing care is unconscionable. Our community needs more evidence-based research, providers, and centers, not politics.

The LGBTQ community and providers are rightfully fearful of the repercussions of such legislation. And the politicians and supporters of such bills should be equally apprehensive of the negative consequences this legislation will have on the mental health of transgender youth.

While the model for gender-affirming medicine and surgery needs continual assessment to ensure all patients, regardless of age and goals of transition, are receiving evidence-based, quality care, these discussions and subsequent decision-making should occur among medical professionals, not among politicians and the lay press.⁴

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

References

1. Hughes LD et al. ‘These laws will be devastating’: Provider perspectives on legislation banning gender-affirming care for transgender adolescents. J Adol Health;2021;69:976-82.

2. Kimberly LL et al. Ethical issues in gender-affirming care for youth. Pediatrics. Pediatrics;018;142(6)e20181537.

3. Ashley F. Psychol Sexual Orient Gender Divers. APA PsycNet. 2021.

4. Ault A. Transgender docs warn about gender-affirmative care for youth. WebMD. 2021 Nov. Accessed March 14, 2022.