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.

Premenopausal women with a family history of breast cancer have a greater volume of breast density observed during mammography, according to a new study of two retrospective cohorts published online Feb. 17 in JAMA Network Open. The findings suggest that breast density measured during mammography may have a genetic component, and suggest the importance of initiating early mammography in premenopausal women with a family history of breast cancer.

“We know that mammographic breast density is a very strong risk factor for breast cancer, probably one of the strongest risk factors, and it’s also a surrogate marker for breast cancer development, especially in premenopausal women. We also know that family history of breast cancer is a strong risk factor for breast cancer as well. Surprisingly, we have very limited information on how these risk factors are related to each other. There have been only two studies that have been done in this field in premenopausal women, and the studies are conflicting. So, we felt that we need to really understand how these two factors are related to each other and whether that would have an impact on modifying or refining mammographic screening in high-risk women,” Adetunji T. Toriola, MD, PhD, MPH, said in an interview. Dr. Toriola is professor of surgery at Washington University, St. Louis.

Previous research identified risk factors for dense breast tissue. A genome-wide association study found 31 genetic loci associated with dense breast tissue, and 17 had a known association with breast cancer risk.

In the JAMA Network Open study, the researchers included data from women who were treated at Washington University’s Joanne Knight Breast Health Center and Siteman Cancer Center. The discovery group included 375 premenopausal women who received annual mammography screening in 2016 and had dense volume and non-dense volume measured during each screen. The validation set drew from 14,040 premenopausal women seen at the centers between 2010 and 2015.

In the discovery group, women with a family history of breast cancer had greater volumetric percent density (odds ratio [OR], 1.25; P < .001). The validation set produced a similar result (OR, 1.30; 95% confidence interval, 1.17-1.45). Subanalyses revealed similar associations in non-Hispanic White and Black or African American women.

The current study included a higher percentage of women with a family history of breast cancer than previous studies, and also controlled for more variables. This may have removed confounding variables that could have affected previous studies.

“It reinforces the need to start mammogram screening early in women who have a family history of breast cancer,” Dr. Toriola said.

The study had some limitations, including a higher percentage of women with a family history of breast cancer than the National Health Interview Survey (23.2% and 15.3%, versus 8.4%), explained by the fact that women with a family history of breast cancer are more likely to seek out screening. The average age of women was on average 47 years, making them closer to perimenopausal than premenopausal.

The study was funded by the National Institutes of Health.

Premenopausal women with a family history of breast cancer have a greater volume of breast density observed during mammography, according to a new study of two retrospective cohorts published online Feb. 17 in JAMA Network Open. The findings suggest that breast density measured during mammography may have a genetic component, and suggest the importance of initiating early mammography in premenopausal women with a family history of breast cancer.

“We know that mammographic breast density is a very strong risk factor for breast cancer, probably one of the strongest risk factors, and it’s also a surrogate marker for breast cancer development, especially in premenopausal women. We also know that family history of breast cancer is a strong risk factor for breast cancer as well. Surprisingly, we have very limited information on how these risk factors are related to each other. There have been only two studies that have been done in this field in premenopausal women, and the studies are conflicting. So, we felt that we need to really understand how these two factors are related to each other and whether that would have an impact on modifying or refining mammographic screening in high-risk women,” Adetunji T. Toriola, MD, PhD, MPH, said in an interview. Dr. Toriola is professor of surgery at Washington University, St. Louis.

Previous research identified risk factors for dense breast tissue. A genome-wide association study found 31 genetic loci associated with dense breast tissue, and 17 had a known association with breast cancer risk.

In the JAMA Network Open study, the researchers included data from women who were treated at Washington University’s Joanne Knight Breast Health Center and Siteman Cancer Center. The discovery group included 375 premenopausal women who received annual mammography screening in 2016 and had dense volume and non-dense volume measured during each screen. The validation set drew from 14,040 premenopausal women seen at the centers between 2010 and 2015.

In the discovery group, women with a family history of breast cancer had greater volumetric percent density (odds ratio [OR], 1.25; P < .001). The validation set produced a similar result (OR, 1.30; 95% confidence interval, 1.17-1.45). Subanalyses revealed similar associations in non-Hispanic White and Black or African American women.

The current study included a higher percentage of women with a family history of breast cancer than previous studies, and also controlled for more variables. This may have removed confounding variables that could have affected previous studies.

“It reinforces the need to start mammogram screening early in women who have a family history of breast cancer,” Dr. Toriola said.

The study had some limitations, including a higher percentage of women with a family history of breast cancer than the National Health Interview Survey (23.2% and 15.3%, versus 8.4%), explained by the fact that women with a family history of breast cancer are more likely to seek out screening. The average age of women was on average 47 years, making them closer to perimenopausal than premenopausal.

The study was funded by the National Institutes of Health.

Premenopausal women with a family history of breast cancer have a greater volume of breast density observed during mammography, according to a new study of two retrospective cohorts published online Feb. 17 in JAMA Network Open. The findings suggest that breast density measured during mammography may have a genetic component, and suggest the importance of initiating early mammography in premenopausal women with a family history of breast cancer.

“We know that mammographic breast density is a very strong risk factor for breast cancer, probably one of the strongest risk factors, and it’s also a surrogate marker for breast cancer development, especially in premenopausal women. We also know that family history of breast cancer is a strong risk factor for breast cancer as well. Surprisingly, we have very limited information on how these risk factors are related to each other. There have been only two studies that have been done in this field in premenopausal women, and the studies are conflicting. So, we felt that we need to really understand how these two factors are related to each other and whether that would have an impact on modifying or refining mammographic screening in high-risk women,” Adetunji T. Toriola, MD, PhD, MPH, said in an interview. Dr. Toriola is professor of surgery at Washington University, St. Louis.

Previous research identified risk factors for dense breast tissue. A genome-wide association study found 31 genetic loci associated with dense breast tissue, and 17 had a known association with breast cancer risk.

In the JAMA Network Open study, the researchers included data from women who were treated at Washington University’s Joanne Knight Breast Health Center and Siteman Cancer Center. The discovery group included 375 premenopausal women who received annual mammography screening in 2016 and had dense volume and non-dense volume measured during each screen. The validation set drew from 14,040 premenopausal women seen at the centers between 2010 and 2015.

In the discovery group, women with a family history of breast cancer had greater volumetric percent density (odds ratio [OR], 1.25; P < .001). The validation set produced a similar result (OR, 1.30; 95% confidence interval, 1.17-1.45). Subanalyses revealed similar associations in non-Hispanic White and Black or African American women.

The current study included a higher percentage of women with a family history of breast cancer than previous studies, and also controlled for more variables. This may have removed confounding variables that could have affected previous studies.

“It reinforces the need to start mammogram screening early in women who have a family history of breast cancer,” Dr. Toriola said.

The study had some limitations, including a higher percentage of women with a family history of breast cancer than the National Health Interview Survey (23.2% and 15.3%, versus 8.4%), explained by the fact that women with a family history of breast cancer are more likely to seek out screening. The average age of women was on average 47 years, making them closer to perimenopausal than premenopausal.

The study was funded by the National Institutes of Health.

One nurse is headed to federal prison and another faces a similar fate for participating in a pair of prison contraband schemes.

Former contract nurse Joseph Nwancha, RN, 41, of Baltimore, Maryland, was sentenced to 30 months in federal prison followed by 3 years of supervised release for his role in a scheme to smuggle narcotics, tobacco, cell phones, and other contraband into a state prison.

In his plea deal, Mr. Nwancha said that he was regularly the on-duty nurse during evenings and nights at Maryland Correctional Institute Jessup, which housed approximately 1,100 male inmates. This made it possible for him to have private contact with inmates without prison employees or other inmates observing the interactions.

According to court documents, beginning in September 2017, Corey Alston, an inmate at the medium-security prison, began bribing Mr. Nwancha to bring contraband into the prison. The inmate’s sister, Ashley Alston, discussed the bribe payments with Mr. Nwancha via text messages and later met with Mr. Nwancha to give him money. In his plea deal, Mr. Nwancha also admitted to having similar arrangements with other inmates.

On Nov. 28, 2017, Mr. Nwancha was stopped at MCIJ and was found to be in possession of approximately 230 g of K2, a synthetic cannabinoid, intended for Mr. Alston and other inmates, according to the court documents. A cell phone recovered from Mr. Nwancha contained text-message conversations discussing bribe payments and other details related to the smuggling operation. The next day, Mr. Nwancha fled to Dublin where he remained until his arrest and extradition, the document says.

According to the Maryland Board of Nursing, Mr. Nwancha earned his license to practice in 2013, and it expired in 2019.

The Washington Post reported that Mr. Nwancha was part of a smuggling ring involving at least 25 people, including corrections officers, in which conspirators would receive “bribes, kickbacks, and sexual favors” in exchange for smuggling contraband into the facility.

Jeane Arnette, RN, of Leavenworth, Kan., pleaded guilty to a scheme in which she used her role as a nurse to smuggle contraband, including cell phones, into the Leavenworth Detention Center.

Ms. Arnette, 61, pleaded guilty on Mach 10 to conspiracy to provide contraband to federal prison inmates. The Kansas City Star says Ms. Arnette worked at the prison from August 2020 through September 2021 and allegedly attempted to smuggle contraband on at least 15 occasions to one inmate. Investigators alleged she was paid through Cash App for the transactions.

She is scheduled to be sentenced June 9 and faces a maximum penalty of 5 years in prison.
 

New York nurse indicted in COVID-19 vaccine card scam

A New York licensed practical nurse faces charges of conspiring to defraud the U.S. Department of Health & Human Services and conspiring to commit forgery in a scheme to distribute and sell false COVID-19 vaccination cards.

According to the indictment, Steven Rodriguez, of Long Beach, N.Y., 27, a nurse at a Hempstead, N.Y.–based clinic, conspired with Jia Liu, 26, of New York, who is a member of the U.S. Marine Corps Reserve, to provide the fake vaccination cards. The cards were sold to unvaccinated Marine Corps reservists who did not want to comply with U.S. Department of Defense vaccination regulations.

In the scheme, Mr. Liu purchased stolen, blank COVID-19 vaccination cards from Mr. Rodriguez, then forged and distributed them for profit. Mr. Liu also directed buyers to meet Mr. Rodriguez in person at the health care clinic where, rather than administer the vaccination, Mr. Rodriguez would destroy the vial of vaccine intended for that patient, then provide a forged vaccination card. Mr. Rodriguez then made false entries in immunization databases indicating that the buyer had been vaccinated. Mr. Liu was also charged with one count of conspiring to defraud the Department of Defense, according to prosecutors.

Using code words such as “gift cards,” “Pokemon cards,” and “Cardi Bs,” the men sent messages on encrypted messaging apps and on social media to inform potential buyers of the opportunity to buy the fake cards, prosecutors said.

Overall, according to the indictment, Mr. Rodriguez and Mr. Liu distributed at least 300 stolen or false COVID-19 vaccination cards, created more than 70 false entries in immunization databases, and destroyed multiple doses of COVID-19 vaccine. “The defendants put military and other communities at risk of contracting a virus that has already claimed nearly one million lives in this country,” Breon Peace, U.S. Attorney for the Eastern District of New York, said when announcing the charges.

Mr. Rodriguez’s lawyer said in an email to The New York Times that the charges are “disturbing” but added, “This young man has no prior record and has a good family, which is why he was released on an unsecured signature bond with the consent of the government.”

Mr. Rodriguez acquired his LPN license in 2018, and it was valid as of press time, according to the New York Office of the Professions database.

Mr. Liu, who also faces charges in connection with the January 6 riot on Capitol Hill, was released on a $250,000 bond to home detention with GPS monitoring, according to the same report.

If convicted, the men could each face up to 10 years in prison.
 

Pennsylvania nurse practitioner faces 22 felony charges

A Bradford County, Pennsylvania, nurse practitioner is facing nearly two dozen felony violations of state law.

Stephanie King, CRNP, 45, of Ulster, Pennsylvania, is accused of prescribing medicines without a collaborating physician, as well as with multiple counts of false billing.

The felony charges include three violations of the state’s Controlled Substance, Drug, Device and Cosmetic Act; two counts of insurance fraud; six counts of Medicaid fraud; six counts of forgery; two counts of tampering with public records; and three counts of theft by deception.

According to local press reports, Ms. King was the owner and operator of the Center for Holistic and Integrative Mental Health in Athens, Pa. The charging documents allege that, beginning in November 2016, Ms. King entered into a sexual relationship with a patient and billed a private insurer for their trysts. Ms. King subsequently entered a relationship with another patient. Although she discontinued medical care for this patient after the affair began, she continued to prescribe controlled substances for him, according to the indictment.

In addition, prosecutors allege that Ms. King renewed previous collaboration agreements without the knowledge of her physician collaborators. Under Pennsylvania law, nurse practitioners are required to enter into collaborative agreements with Pennsylvania-licensed physicians in order to perform medical diagnoses and prescribe controlled substances.

The investigation found that Ms. King falsely billed more than $300,000 to private insurers and $100,000 to the Commonwealth of Pennsylvania for services that did not meet acceptable medical treatment standards. In addition, she is alleged to have written more than 3,750 prescriptions to patients during the time she did not meet the State of Pennsylvania’s requirements to prescribe.

Her license, originally obtained in 2011, was suspended on March 25, 2020.
 

Massachusetts nurse pleads guilty of tampering with patients’ fentanyl

A Massachusetts nurse was charged with and has agreed to plead guilty to one count of tampering with a controlled substance while working in the postsurgery recovery unit at a Massachusetts hospital as well as at an outpatient vascular surgery center.

According to the charging documents, Hugo Vieira, 41, of Berkley, Massachusetts, removed fentanyl from vials meant for patients undergoing or recovering from surgery. He then replaced the fentanyl with saline. Investigators identified 60 vials that had been tampered with at the vascular surgery center and two at the hospital.

Mr. Viera faces up to 10 years in prison followed by 3 years of supervised release and a fine of up to $250,000 for the tampering charge.

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

One nurse is headed to federal prison and another faces a similar fate for participating in a pair of prison contraband schemes.

Former contract nurse Joseph Nwancha, RN, 41, of Baltimore, Maryland, was sentenced to 30 months in federal prison followed by 3 years of supervised release for his role in a scheme to smuggle narcotics, tobacco, cell phones, and other contraband into a state prison.

In his plea deal, Mr. Nwancha said that he was regularly the on-duty nurse during evenings and nights at Maryland Correctional Institute Jessup, which housed approximately 1,100 male inmates. This made it possible for him to have private contact with inmates without prison employees or other inmates observing the interactions.

According to court documents, beginning in September 2017, Corey Alston, an inmate at the medium-security prison, began bribing Mr. Nwancha to bring contraband into the prison. The inmate’s sister, Ashley Alston, discussed the bribe payments with Mr. Nwancha via text messages and later met with Mr. Nwancha to give him money. In his plea deal, Mr. Nwancha also admitted to having similar arrangements with other inmates.

On Nov. 28, 2017, Mr. Nwancha was stopped at MCIJ and was found to be in possession of approximately 230 g of K2, a synthetic cannabinoid, intended for Mr. Alston and other inmates, according to the court documents. A cell phone recovered from Mr. Nwancha contained text-message conversations discussing bribe payments and other details related to the smuggling operation. The next day, Mr. Nwancha fled to Dublin where he remained until his arrest and extradition, the document says.

According to the Maryland Board of Nursing, Mr. Nwancha earned his license to practice in 2013, and it expired in 2019.

The Washington Post reported that Mr. Nwancha was part of a smuggling ring involving at least 25 people, including corrections officers, in which conspirators would receive “bribes, kickbacks, and sexual favors” in exchange for smuggling contraband into the facility.

Jeane Arnette, RN, of Leavenworth, Kan., pleaded guilty to a scheme in which she used her role as a nurse to smuggle contraband, including cell phones, into the Leavenworth Detention Center.

Ms. Arnette, 61, pleaded guilty on Mach 10 to conspiracy to provide contraband to federal prison inmates. The Kansas City Star says Ms. Arnette worked at the prison from August 2020 through September 2021 and allegedly attempted to smuggle contraband on at least 15 occasions to one inmate. Investigators alleged she was paid through Cash App for the transactions.

She is scheduled to be sentenced June 9 and faces a maximum penalty of 5 years in prison.
 

New York nurse indicted in COVID-19 vaccine card scam

A New York licensed practical nurse faces charges of conspiring to defraud the U.S. Department of Health & Human Services and conspiring to commit forgery in a scheme to distribute and sell false COVID-19 vaccination cards.

According to the indictment, Steven Rodriguez, of Long Beach, N.Y., 27, a nurse at a Hempstead, N.Y.–based clinic, conspired with Jia Liu, 26, of New York, who is a member of the U.S. Marine Corps Reserve, to provide the fake vaccination cards. The cards were sold to unvaccinated Marine Corps reservists who did not want to comply with U.S. Department of Defense vaccination regulations.

In the scheme, Mr. Liu purchased stolen, blank COVID-19 vaccination cards from Mr. Rodriguez, then forged and distributed them for profit. Mr. Liu also directed buyers to meet Mr. Rodriguez in person at the health care clinic where, rather than administer the vaccination, Mr. Rodriguez would destroy the vial of vaccine intended for that patient, then provide a forged vaccination card. Mr. Rodriguez then made false entries in immunization databases indicating that the buyer had been vaccinated. Mr. Liu was also charged with one count of conspiring to defraud the Department of Defense, according to prosecutors.

Using code words such as “gift cards,” “Pokemon cards,” and “Cardi Bs,” the men sent messages on encrypted messaging apps and on social media to inform potential buyers of the opportunity to buy the fake cards, prosecutors said.

Overall, according to the indictment, Mr. Rodriguez and Mr. Liu distributed at least 300 stolen or false COVID-19 vaccination cards, created more than 70 false entries in immunization databases, and destroyed multiple doses of COVID-19 vaccine. “The defendants put military and other communities at risk of contracting a virus that has already claimed nearly one million lives in this country,” Breon Peace, U.S. Attorney for the Eastern District of New York, said when announcing the charges.

Mr. Rodriguez’s lawyer said in an email to The New York Times that the charges are “disturbing” but added, “This young man has no prior record and has a good family, which is why he was released on an unsecured signature bond with the consent of the government.”

Mr. Rodriguez acquired his LPN license in 2018, and it was valid as of press time, according to the New York Office of the Professions database.

Mr. Liu, who also faces charges in connection with the January 6 riot on Capitol Hill, was released on a $250,000 bond to home detention with GPS monitoring, according to the same report.

If convicted, the men could each face up to 10 years in prison.
 

Pennsylvania nurse practitioner faces 22 felony charges

A Bradford County, Pennsylvania, nurse practitioner is facing nearly two dozen felony violations of state law.

Stephanie King, CRNP, 45, of Ulster, Pennsylvania, is accused of prescribing medicines without a collaborating physician, as well as with multiple counts of false billing.

The felony charges include three violations of the state’s Controlled Substance, Drug, Device and Cosmetic Act; two counts of insurance fraud; six counts of Medicaid fraud; six counts of forgery; two counts of tampering with public records; and three counts of theft by deception.

According to local press reports, Ms. King was the owner and operator of the Center for Holistic and Integrative Mental Health in Athens, Pa. The charging documents allege that, beginning in November 2016, Ms. King entered into a sexual relationship with a patient and billed a private insurer for their trysts. Ms. King subsequently entered a relationship with another patient. Although she discontinued medical care for this patient after the affair began, she continued to prescribe controlled substances for him, according to the indictment.

In addition, prosecutors allege that Ms. King renewed previous collaboration agreements without the knowledge of her physician collaborators. Under Pennsylvania law, nurse practitioners are required to enter into collaborative agreements with Pennsylvania-licensed physicians in order to perform medical diagnoses and prescribe controlled substances.

The investigation found that Ms. King falsely billed more than $300,000 to private insurers and $100,000 to the Commonwealth of Pennsylvania for services that did not meet acceptable medical treatment standards. In addition, she is alleged to have written more than 3,750 prescriptions to patients during the time she did not meet the State of Pennsylvania’s requirements to prescribe.

Her license, originally obtained in 2011, was suspended on March 25, 2020.
 

Massachusetts nurse pleads guilty of tampering with patients’ fentanyl

A Massachusetts nurse was charged with and has agreed to plead guilty to one count of tampering with a controlled substance while working in the postsurgery recovery unit at a Massachusetts hospital as well as at an outpatient vascular surgery center.

According to the charging documents, Hugo Vieira, 41, of Berkley, Massachusetts, removed fentanyl from vials meant for patients undergoing or recovering from surgery. He then replaced the fentanyl with saline. Investigators identified 60 vials that had been tampered with at the vascular surgery center and two at the hospital.

Mr. Viera faces up to 10 years in prison followed by 3 years of supervised release and a fine of up to $250,000 for the tampering charge.

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

One nurse is headed to federal prison and another faces a similar fate for participating in a pair of prison contraband schemes.

Former contract nurse Joseph Nwancha, RN, 41, of Baltimore, Maryland, was sentenced to 30 months in federal prison followed by 3 years of supervised release for his role in a scheme to smuggle narcotics, tobacco, cell phones, and other contraband into a state prison.

In his plea deal, Mr. Nwancha said that he was regularly the on-duty nurse during evenings and nights at Maryland Correctional Institute Jessup, which housed approximately 1,100 male inmates. This made it possible for him to have private contact with inmates without prison employees or other inmates observing the interactions.

According to court documents, beginning in September 2017, Corey Alston, an inmate at the medium-security prison, began bribing Mr. Nwancha to bring contraband into the prison. The inmate’s sister, Ashley Alston, discussed the bribe payments with Mr. Nwancha via text messages and later met with Mr. Nwancha to give him money. In his plea deal, Mr. Nwancha also admitted to having similar arrangements with other inmates.

On Nov. 28, 2017, Mr. Nwancha was stopped at MCIJ and was found to be in possession of approximately 230 g of K2, a synthetic cannabinoid, intended for Mr. Alston and other inmates, according to the court documents. A cell phone recovered from Mr. Nwancha contained text-message conversations discussing bribe payments and other details related to the smuggling operation. The next day, Mr. Nwancha fled to Dublin where he remained until his arrest and extradition, the document says.

According to the Maryland Board of Nursing, Mr. Nwancha earned his license to practice in 2013, and it expired in 2019.

The Washington Post reported that Mr. Nwancha was part of a smuggling ring involving at least 25 people, including corrections officers, in which conspirators would receive “bribes, kickbacks, and sexual favors” in exchange for smuggling contraband into the facility.

Jeane Arnette, RN, of Leavenworth, Kan., pleaded guilty to a scheme in which she used her role as a nurse to smuggle contraband, including cell phones, into the Leavenworth Detention Center.

Ms. Arnette, 61, pleaded guilty on Mach 10 to conspiracy to provide contraband to federal prison inmates. The Kansas City Star says Ms. Arnette worked at the prison from August 2020 through September 2021 and allegedly attempted to smuggle contraband on at least 15 occasions to one inmate. Investigators alleged she was paid through Cash App for the transactions.

She is scheduled to be sentenced June 9 and faces a maximum penalty of 5 years in prison.
 

New York nurse indicted in COVID-19 vaccine card scam

A New York licensed practical nurse faces charges of conspiring to defraud the U.S. Department of Health & Human Services and conspiring to commit forgery in a scheme to distribute and sell false COVID-19 vaccination cards.

According to the indictment, Steven Rodriguez, of Long Beach, N.Y., 27, a nurse at a Hempstead, N.Y.–based clinic, conspired with Jia Liu, 26, of New York, who is a member of the U.S. Marine Corps Reserve, to provide the fake vaccination cards. The cards were sold to unvaccinated Marine Corps reservists who did not want to comply with U.S. Department of Defense vaccination regulations.

In the scheme, Mr. Liu purchased stolen, blank COVID-19 vaccination cards from Mr. Rodriguez, then forged and distributed them for profit. Mr. Liu also directed buyers to meet Mr. Rodriguez in person at the health care clinic where, rather than administer the vaccination, Mr. Rodriguez would destroy the vial of vaccine intended for that patient, then provide a forged vaccination card. Mr. Rodriguez then made false entries in immunization databases indicating that the buyer had been vaccinated. Mr. Liu was also charged with one count of conspiring to defraud the Department of Defense, according to prosecutors.

Using code words such as “gift cards,” “Pokemon cards,” and “Cardi Bs,” the men sent messages on encrypted messaging apps and on social media to inform potential buyers of the opportunity to buy the fake cards, prosecutors said.

Overall, according to the indictment, Mr. Rodriguez and Mr. Liu distributed at least 300 stolen or false COVID-19 vaccination cards, created more than 70 false entries in immunization databases, and destroyed multiple doses of COVID-19 vaccine. “The defendants put military and other communities at risk of contracting a virus that has already claimed nearly one million lives in this country,” Breon Peace, U.S. Attorney for the Eastern District of New York, said when announcing the charges.

Mr. Rodriguez’s lawyer said in an email to The New York Times that the charges are “disturbing” but added, “This young man has no prior record and has a good family, which is why he was released on an unsecured signature bond with the consent of the government.”

Mr. Rodriguez acquired his LPN license in 2018, and it was valid as of press time, according to the New York Office of the Professions database.

Mr. Liu, who also faces charges in connection with the January 6 riot on Capitol Hill, was released on a $250,000 bond to home detention with GPS monitoring, according to the same report.

If convicted, the men could each face up to 10 years in prison.
 

Pennsylvania nurse practitioner faces 22 felony charges

A Bradford County, Pennsylvania, nurse practitioner is facing nearly two dozen felony violations of state law.

Stephanie King, CRNP, 45, of Ulster, Pennsylvania, is accused of prescribing medicines without a collaborating physician, as well as with multiple counts of false billing.

The felony charges include three violations of the state’s Controlled Substance, Drug, Device and Cosmetic Act; two counts of insurance fraud; six counts of Medicaid fraud; six counts of forgery; two counts of tampering with public records; and three counts of theft by deception.

According to local press reports, Ms. King was the owner and operator of the Center for Holistic and Integrative Mental Health in Athens, Pa. The charging documents allege that, beginning in November 2016, Ms. King entered into a sexual relationship with a patient and billed a private insurer for their trysts. Ms. King subsequently entered a relationship with another patient. Although she discontinued medical care for this patient after the affair began, she continued to prescribe controlled substances for him, according to the indictment.

In addition, prosecutors allege that Ms. King renewed previous collaboration agreements without the knowledge of her physician collaborators. Under Pennsylvania law, nurse practitioners are required to enter into collaborative agreements with Pennsylvania-licensed physicians in order to perform medical diagnoses and prescribe controlled substances.

The investigation found that Ms. King falsely billed more than $300,000 to private insurers and $100,000 to the Commonwealth of Pennsylvania for services that did not meet acceptable medical treatment standards. In addition, she is alleged to have written more than 3,750 prescriptions to patients during the time she did not meet the State of Pennsylvania’s requirements to prescribe.

Her license, originally obtained in 2011, was suspended on March 25, 2020.
 

Massachusetts nurse pleads guilty of tampering with patients’ fentanyl

A Massachusetts nurse was charged with and has agreed to plead guilty to one count of tampering with a controlled substance while working in the postsurgery recovery unit at a Massachusetts hospital as well as at an outpatient vascular surgery center.

According to the charging documents, Hugo Vieira, 41, of Berkley, Massachusetts, removed fentanyl from vials meant for patients undergoing or recovering from surgery. He then replaced the fentanyl with saline. Investigators identified 60 vials that had been tampered with at the vascular surgery center and two at the hospital.

Mr. Viera faces up to 10 years in prison followed by 3 years of supervised release and a fine of up to $250,000 for the tampering charge.

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