MDedge ObGyn

This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”

It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.

Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.

Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.

And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.

As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.

Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.

An Ever-Expanding Armamentarium

All of this is telling us how we need to ramp up our game if we are going to be able to use our immune system to quash a cancer. Fortunately, we have abundant and ever-growing capabilities for doing just that.

Immune Checkpoint Inhibitors

The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.

But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.

Therapeutic Cancer Vaccines

There are many therapeutic cancer vaccines in the works, as reviewed in depth here.

Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.

An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.

Antibody-Drug Conjugates (ADC)

There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.

A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.

This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.

Oncolytic Viruses

Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.

After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.

Engineering T Cells (Chimeric Antigen Receptor [CAR-T])

As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.

As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.

Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.

Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.

Summary

Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.

Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.

Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.

Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.

Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.

A version of this article appeared on Medscape.com.

This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”

It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.

Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.

Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.

And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.

As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.

Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.

An Ever-Expanding Armamentarium

All of this is telling us how we need to ramp up our game if we are going to be able to use our immune system to quash a cancer. Fortunately, we have abundant and ever-growing capabilities for doing just that.

Immune Checkpoint Inhibitors

The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.

But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.

Therapeutic Cancer Vaccines

There are many therapeutic cancer vaccines in the works, as reviewed in depth here.

Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.

An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.

Antibody-Drug Conjugates (ADC)

There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.

A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.

This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.

Oncolytic Viruses

Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.

After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.

Engineering T Cells (Chimeric Antigen Receptor [CAR-T])

As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.

As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.

Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.

Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.

Summary

Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.

Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.

Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.

Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.

Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.

A version of this article appeared on Medscape.com.

This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”

It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.

Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.

Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.

And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.

As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.

Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.

An Ever-Expanding Armamentarium

All of this is telling us how we need to ramp up our game if we are going to be able to use our immune system to quash a cancer. Fortunately, we have abundant and ever-growing capabilities for doing just that.

Immune Checkpoint Inhibitors

The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.

But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.

Therapeutic Cancer Vaccines

There are many therapeutic cancer vaccines in the works, as reviewed in depth here.

Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.

An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.

Antibody-Drug Conjugates (ADC)

There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.

A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.

This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.

Oncolytic Viruses

Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.

After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.

Engineering T Cells (Chimeric Antigen Receptor [CAR-T])

As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.

As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.

Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.

Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.

Summary

Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.

Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.

Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.

Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.

Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.

A version of this article appeared on Medscape.com.

TOPLINE:

Cefepime-taniborbactam was 22% more effective than meropenem, which is a current treatment for complicated urinary tract infections (UTIs) and acute pyelonephritis, according to a study published in The New England Journal of Medicine.

METHODOLOGY:

• Cefepime-taniborbactam is an antibiotic currently being explored as a treatment for antibiotic-resistant bacteria.
• The phase 3, double-blind, randomized trial included participants from 15 countries, including a safety group of 657 patients who were studied for adverse events and 436 in the micro intention-to-treat group who were studied for drug effectiveness.
• Each drug’s efficacy was measured as a combination of reduced bacteria levels and a resolution of symptoms and signs of infection.
• Patients in the study were over age 18; had a diagnosis of either complicated UTI or acute pyelonephritis; and had pyuria, at least one systemic sign, and at least one local sign or symptom. People were excluded if they had already received antibacterial drug therapy for more than 24 hours before randomization or had an infection with a meropenem-resistant pathogen.

TAKEAWAY:

• At days 19-23, 70.6% of patients in the cefepime-taniborbactam group showed a successful reduction in bacteria and symptoms compared with 58.0% in the meropenem group.
• Cefepime-taniborbactam was more effective than meropenem during follow-up, with 89.1% efficacy less than 24 hours after the last dose, compared to meropenem’s 86%. Cefepime-taniborbactam continued to have 63.8% efficacy up to 35 days after starting treatment, while meropenem was 51.7% during that timeframe.
• In the cefepime-taniborbactam group, 35.5% of patients experienced adverse effects that were mild to moderate, including headache, diarrhea, constipation, hypertension, and nausea, compared to 29% in the meropenem group.
• Overall, 3% of participants discontinued cefepime-taniborbactam and 1.8% discontinued meropenem, but reasons were heterogeneous.

IN PRACTICE:

“Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem,” the study authors wrote.

SOURCE:

Paul McGovern, MD, infectious disease specialist and senior vice president of Venatorx Pharmaceuticals, was the corresponding author of the study.

LIMITATIONS:

The authors reported no limitations.

DISCLOSURES:

The study was funded by Venatorx Pharmaceuticals, which received funding from the US Department of Health and Human Services, the Administration for Strategic Preparedness and Response, the Biomedical Advanced Research and Development Authority, the Global Antibiotic Research and Development Partnership, and Everest Medicines.

A version of this article appeared on Medscape.com.

TOPLINE:

Cefepime-taniborbactam was 22% more effective than meropenem, which is a current treatment for complicated urinary tract infections (UTIs) and acute pyelonephritis, according to a study published in The New England Journal of Medicine.

METHODOLOGY:

• Cefepime-taniborbactam is an antibiotic currently being explored as a treatment for antibiotic-resistant bacteria.
• The phase 3, double-blind, randomized trial included participants from 15 countries, including a safety group of 657 patients who were studied for adverse events and 436 in the micro intention-to-treat group who were studied for drug effectiveness.
• Each drug’s efficacy was measured as a combination of reduced bacteria levels and a resolution of symptoms and signs of infection.
• Patients in the study were over age 18; had a diagnosis of either complicated UTI or acute pyelonephritis; and had pyuria, at least one systemic sign, and at least one local sign or symptom. People were excluded if they had already received antibacterial drug therapy for more than 24 hours before randomization or had an infection with a meropenem-resistant pathogen.

TAKEAWAY:

• At days 19-23, 70.6% of patients in the cefepime-taniborbactam group showed a successful reduction in bacteria and symptoms compared with 58.0% in the meropenem group.
• Cefepime-taniborbactam was more effective than meropenem during follow-up, with 89.1% efficacy less than 24 hours after the last dose, compared to meropenem’s 86%. Cefepime-taniborbactam continued to have 63.8% efficacy up to 35 days after starting treatment, while meropenem was 51.7% during that timeframe.
• In the cefepime-taniborbactam group, 35.5% of patients experienced adverse effects that were mild to moderate, including headache, diarrhea, constipation, hypertension, and nausea, compared to 29% in the meropenem group.
• Overall, 3% of participants discontinued cefepime-taniborbactam and 1.8% discontinued meropenem, but reasons were heterogeneous.

IN PRACTICE:

“Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem,” the study authors wrote.

SOURCE:

Paul McGovern, MD, infectious disease specialist and senior vice president of Venatorx Pharmaceuticals, was the corresponding author of the study.

LIMITATIONS:

The authors reported no limitations.

DISCLOSURES:

The study was funded by Venatorx Pharmaceuticals, which received funding from the US Department of Health and Human Services, the Administration for Strategic Preparedness and Response, the Biomedical Advanced Research and Development Authority, the Global Antibiotic Research and Development Partnership, and Everest Medicines.

A version of this article appeared on Medscape.com.

TOPLINE:

Cefepime-taniborbactam was 22% more effective than meropenem, which is a current treatment for complicated urinary tract infections (UTIs) and acute pyelonephritis, according to a study published in The New England Journal of Medicine.

METHODOLOGY:

• Cefepime-taniborbactam is an antibiotic currently being explored as a treatment for antibiotic-resistant bacteria.
• The phase 3, double-blind, randomized trial included participants from 15 countries, including a safety group of 657 patients who were studied for adverse events and 436 in the micro intention-to-treat group who were studied for drug effectiveness.
• Each drug’s efficacy was measured as a combination of reduced bacteria levels and a resolution of symptoms and signs of infection.
• Patients in the study were over age 18; had a diagnosis of either complicated UTI or acute pyelonephritis; and had pyuria, at least one systemic sign, and at least one local sign or symptom. People were excluded if they had already received antibacterial drug therapy for more than 24 hours before randomization or had an infection with a meropenem-resistant pathogen.

TAKEAWAY:

• At days 19-23, 70.6% of patients in the cefepime-taniborbactam group showed a successful reduction in bacteria and symptoms compared with 58.0% in the meropenem group.
• Cefepime-taniborbactam was more effective than meropenem during follow-up, with 89.1% efficacy less than 24 hours after the last dose, compared to meropenem’s 86%. Cefepime-taniborbactam continued to have 63.8% efficacy up to 35 days after starting treatment, while meropenem was 51.7% during that timeframe.
• In the cefepime-taniborbactam group, 35.5% of patients experienced adverse effects that were mild to moderate, including headache, diarrhea, constipation, hypertension, and nausea, compared to 29% in the meropenem group.
• Overall, 3% of participants discontinued cefepime-taniborbactam and 1.8% discontinued meropenem, but reasons were heterogeneous.

IN PRACTICE:

“Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem,” the study authors wrote.

SOURCE:

Paul McGovern, MD, infectious disease specialist and senior vice president of Venatorx Pharmaceuticals, was the corresponding author of the study.

LIMITATIONS:

The authors reported no limitations.

DISCLOSURES:

The study was funded by Venatorx Pharmaceuticals, which received funding from the US Department of Health and Human Services, the Administration for Strategic Preparedness and Response, the Biomedical Advanced Research and Development Authority, the Global Antibiotic Research and Development Partnership, and Everest Medicines.

A version of this article appeared on Medscape.com.

Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.

The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.

“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.

Perelman School of Medicine

“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.

“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.

APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.

Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.

The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.

An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.

Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.

Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.

Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”

Northwestern Medicine

Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.

The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.

“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.

Perelman School of Medicine

“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.

“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.

APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.

Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.

The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.

An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.

Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.

Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.

Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”

Northwestern Medicine

Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.

The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.

“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.

Perelman School of Medicine

“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.

“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.

APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.

Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.

The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.

An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.

Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.

Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.

Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”

Northwestern Medicine

TOPLINE:

Higher body mass index (BMI) at the start of pregnancy is associated with increased risk for adverse maternal outcomes, including preeclampsia, and neonatal complications, such as respiratory distress syndrome (RDS), in a dose-dependent manner, new research shows.

METHODOLOGY:

• Researchers conducted a retrospective study of 58,497 singleton pregnancies delivered at an urban hospital between 2013 and 2021.
• They focused on pregnancies delivered between 24 and 42 weeks of gestation, for which information about BMI at the first prenatal visit was available.
• 21.1% of mothers had class I , 9.3% had class II obesity, and 6% had class III obesity.

TAKEAWAY: 

• Obesity was associated with a dose-dependent increase in cesarean deliveries (27% of deliveries without obesity vs 46% of deliveries with class III obesity).
• Severe preeclampsia occurred in 8% of mothers without obesity and in 19% of mothers with class III obesity.
• Infants born to mothers with class III obesity were more likely than were infants born to mothers without obesity to have RDS, with a relative risk (RR) of 2.66.
• With class II obesity, the RR was 1.77. With class I obesity, the RR was 1.3.
• Obesity also was associated with increased risk for grade III-IV  (RR), 4.58 for class III obesity) and  (RR, 3.76).

IN PRACTICE:

“Infants born to patients with higher classes of obesity have significant associated morbidity including a 2 to 4 times increased risk of neonatal acidosis, grades III-IV intraventricular hemorrhage, sepsis, and RDS,” the researchers reported. 

SOURCE:

Sara I. Jones, MD, with University of Texas Southwestern Medical Center in Dallas, presented the study on February 14 at the 2024 Pregnancy Meeting of the Society for Maternal-Fetal Medicine, in National Harbor, Maryland. 

DISCLOSURES:

The researchers had no conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Higher body mass index (BMI) at the start of pregnancy is associated with increased risk for adverse maternal outcomes, including preeclampsia, and neonatal complications, such as respiratory distress syndrome (RDS), in a dose-dependent manner, new research shows.

METHODOLOGY:

• Researchers conducted a retrospective study of 58,497 singleton pregnancies delivered at an urban hospital between 2013 and 2021.
• They focused on pregnancies delivered between 24 and 42 weeks of gestation, for which information about BMI at the first prenatal visit was available.
• 21.1% of mothers had class I , 9.3% had class II obesity, and 6% had class III obesity.

TAKEAWAY: 

• Obesity was associated with a dose-dependent increase in cesarean deliveries (27% of deliveries without obesity vs 46% of deliveries with class III obesity).
• Severe preeclampsia occurred in 8% of mothers without obesity and in 19% of mothers with class III obesity.
• Infants born to mothers with class III obesity were more likely than were infants born to mothers without obesity to have RDS, with a relative risk (RR) of 2.66.
• With class II obesity, the RR was 1.77. With class I obesity, the RR was 1.3.
• Obesity also was associated with increased risk for grade III-IV  (RR), 4.58 for class III obesity) and  (RR, 3.76).

IN PRACTICE:

“Infants born to patients with higher classes of obesity have significant associated morbidity including a 2 to 4 times increased risk of neonatal acidosis, grades III-IV intraventricular hemorrhage, sepsis, and RDS,” the researchers reported. 

SOURCE:

Sara I. Jones, MD, with University of Texas Southwestern Medical Center in Dallas, presented the study on February 14 at the 2024 Pregnancy Meeting of the Society for Maternal-Fetal Medicine, in National Harbor, Maryland. 

DISCLOSURES:

The researchers had no conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Higher body mass index (BMI) at the start of pregnancy is associated with increased risk for adverse maternal outcomes, including preeclampsia, and neonatal complications, such as respiratory distress syndrome (RDS), in a dose-dependent manner, new research shows.

METHODOLOGY:

• Researchers conducted a retrospective study of 58,497 singleton pregnancies delivered at an urban hospital between 2013 and 2021.
• They focused on pregnancies delivered between 24 and 42 weeks of gestation, for which information about BMI at the first prenatal visit was available.
• 21.1% of mothers had class I , 9.3% had class II obesity, and 6% had class III obesity.

TAKEAWAY: 

• Obesity was associated with a dose-dependent increase in cesarean deliveries (27% of deliveries without obesity vs 46% of deliveries with class III obesity).
• Severe preeclampsia occurred in 8% of mothers without obesity and in 19% of mothers with class III obesity.
• Infants born to mothers with class III obesity were more likely than were infants born to mothers without obesity to have RDS, with a relative risk (RR) of 2.66.
• With class II obesity, the RR was 1.77. With class I obesity, the RR was 1.3.
• Obesity also was associated with increased risk for grade III-IV  (RR), 4.58 for class III obesity) and  (RR, 3.76).

IN PRACTICE:

“Infants born to patients with higher classes of obesity have significant associated morbidity including a 2 to 4 times increased risk of neonatal acidosis, grades III-IV intraventricular hemorrhage, sepsis, and RDS,” the researchers reported. 

SOURCE:

Sara I. Jones, MD, with University of Texas Southwestern Medical Center in Dallas, presented the study on February 14 at the 2024 Pregnancy Meeting of the Society for Maternal-Fetal Medicine, in National Harbor, Maryland. 

DISCLOSURES:

The researchers had no conflicts of interest to disclose.

A version of this article appeared on Medscape.com.

A trio of studies (abstracts 1101, 1079, and 944) presented on February 14 at the meeting sponsored by the Society for Maternal-Fetal Medicine point to the power of staying physically active during pregnancy. The work highlights the beneficial effects of exercise on a variety of outcomes, including depression, anxiety, and reducing the rate of cesarean deliveries.

“Twenty-plus years ago, there were so many recommendations for bed rest in pregnancy,” said Danielle Panelli, MD, a maternal-fetal medicine physician and research scholar at Stanford University in Stanford, California. “We’ve really come full circle on that.” The American College of Obstetricians and Gynecologists recommends pregnant people get at least 150 minutes of moderate activity or 75 minutes of vigorous activity per week. 

Dr. Panelli and colleagues looked at the association of physical activity and anxiety among three groups of pregnant people: 20 outpatients from low-risk obstetric clinics, 20 outpatients from high-risk obstetric clinics, and 19 inpatients. Participants wore accelerometer watches for up to seven days to measure physical activity. The primary outcome was mean daily step count, with secondary outcomes including metabolic equivalent tasks (METs), moderate to vigorous physical activity (MVPA), and anxiety as measured using the State-Trait Anxiety Inventory. 

Low-risk outpatients had an average daily step count of 9090 compared with high-risk outpatients at 8898 and inpatients at 6493. Compared with outpatients, inpatients also had significantly lower METs (adjusted beta, -0.20; 95% CI -0.26 to -0.13; P < .001), and MVPAs (adjusted beta, -43.6; 95% CI, -61.2 to -25.9; P < .001). Over the course of a week, steps progressively decreased for inpatients but not for women in either of the outpatient groups. Among the entire cohort, lower step counts correlated with higher anxiety scores (r = 0.30; P = .02).

“These results highlight the need for physical activity interventions, particularly for hospitalized pregnant people,” Dr. Panelli said. That could be something as simple as asking patients to walk three laps around the unit per day, she suggested.

A second study investigated the effect of physical activity during pregnancy on peripartum depression. Researchers at the University of Alabama at Birmingham reviewed data from participants in nuMoM2b, a large cohort study of pregnant women who would be delivering for the first time and had at least one medical comorbidity, such as chronic hypertension, asthma, or cardiac disease. The investigators looked at activity logs maintained by study participants and turned in at three study visits: 6-13.6 weeks, 14-21.6 weeks, and 22-29.6 weeks. 

Being physically active was associated with 15% lower odds of having an Edinburgh Postnatal Depression Score (EPDS) > 10 (adjusted odds ratio, 0.85; 95% CI, 0.72-0.99). Nine percent of people in the active group and 12% of people in the nonactive group had an EPDS > 10, which is suggestive of depression. However, a change in EPDS from visit one to three and treatment for perinatal depression did not differ by physical activity. 

“One of the interesting findings are that we didn’t see any safety signals [from exercise], so there wasn’t an increase in suspected fetal growth restriction or low fluid or preterm birth, or actual birthweight being low in the people who were active,” said Charlotte McCarley, MD, a maternal-fetal medicine fellow at the University of Alabama at Birmingham, who led the research. “A lot of studies have been done that have looked at prospective exercise in pregnancy, but they exclude the cohort that we looked at for concern that there may be a safety issue.” 

In a third study, researchers at the Rambam Health Care Campus in Haifa, Israel, looked at the effect of physical activity on mode of delivery. The prospective observational analysis included 401 women with singleton pregnancies attempting vaginal deliveries. 

The researchers tracked the number of daily steps taken during gestation using validated phone apps. They adjusted their findings for age, parity, body mass index, and medical and obstetric history. 

The investigators observed a gradual decrease in physical activity as pregnancy progressed (mean of 3184 steps in the first trimester, 2700 steps in mid-pregnancy, and 2152 steps in the third trimester). The overall incidence of cesarean delivery was 10.5%. However, women who were more active during pregnancy had a significantly lower incidence of cesarean delivery. 

Area under the ROC curve, with a cut-off of 2093.5 daily steps, was 0.694 (95% CI, 0.615-0.773), resulting in a significant risk reduction in a 78% reduction in the rate of cesarean surgery (odds ratio, 0.22; 95% CI, 0.104-0.465).

More active patients also had a reduced composite outcome of gestational diabetes, gestational hypertension, and preeclampsia; less use of epidural analgesia during labor; and less postpartum hemorrhage. Preterm birth, labor induction, neonatal weight, and admission to the neonatal intensive care unit were not significantly affected, the researchers reported. 

“Maintaining an active lifestyle during pregnancy should be strongly encouraged,” they wrote. 

The investigators disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

A trio of studies (abstracts 1101, 1079, and 944) presented on February 14 at the meeting sponsored by the Society for Maternal-Fetal Medicine point to the power of staying physically active during pregnancy. The work highlights the beneficial effects of exercise on a variety of outcomes, including depression, anxiety, and reducing the rate of cesarean deliveries.

“Twenty-plus years ago, there were so many recommendations for bed rest in pregnancy,” said Danielle Panelli, MD, a maternal-fetal medicine physician and research scholar at Stanford University in Stanford, California. “We’ve really come full circle on that.” The American College of Obstetricians and Gynecologists recommends pregnant people get at least 150 minutes of moderate activity or 75 minutes of vigorous activity per week. 

Dr. Panelli and colleagues looked at the association of physical activity and anxiety among three groups of pregnant people: 20 outpatients from low-risk obstetric clinics, 20 outpatients from high-risk obstetric clinics, and 19 inpatients. Participants wore accelerometer watches for up to seven days to measure physical activity. The primary outcome was mean daily step count, with secondary outcomes including metabolic equivalent tasks (METs), moderate to vigorous physical activity (MVPA), and anxiety as measured using the State-Trait Anxiety Inventory. 

Low-risk outpatients had an average daily step count of 9090 compared with high-risk outpatients at 8898 and inpatients at 6493. Compared with outpatients, inpatients also had significantly lower METs (adjusted beta, -0.20; 95% CI -0.26 to -0.13; P < .001), and MVPAs (adjusted beta, -43.6; 95% CI, -61.2 to -25.9; P < .001). Over the course of a week, steps progressively decreased for inpatients but not for women in either of the outpatient groups. Among the entire cohort, lower step counts correlated with higher anxiety scores (r = 0.30; P = .02).

“These results highlight the need for physical activity interventions, particularly for hospitalized pregnant people,” Dr. Panelli said. That could be something as simple as asking patients to walk three laps around the unit per day, she suggested.

A second study investigated the effect of physical activity during pregnancy on peripartum depression. Researchers at the University of Alabama at Birmingham reviewed data from participants in nuMoM2b, a large cohort study of pregnant women who would be delivering for the first time and had at least one medical comorbidity, such as chronic hypertension, asthma, or cardiac disease. The investigators looked at activity logs maintained by study participants and turned in at three study visits: 6-13.6 weeks, 14-21.6 weeks, and 22-29.6 weeks. 

Being physically active was associated with 15% lower odds of having an Edinburgh Postnatal Depression Score (EPDS) > 10 (adjusted odds ratio, 0.85; 95% CI, 0.72-0.99). Nine percent of people in the active group and 12% of people in the nonactive group had an EPDS > 10, which is suggestive of depression. However, a change in EPDS from visit one to three and treatment for perinatal depression did not differ by physical activity. 

“One of the interesting findings are that we didn’t see any safety signals [from exercise], so there wasn’t an increase in suspected fetal growth restriction or low fluid or preterm birth, or actual birthweight being low in the people who were active,” said Charlotte McCarley, MD, a maternal-fetal medicine fellow at the University of Alabama at Birmingham, who led the research. “A lot of studies have been done that have looked at prospective exercise in pregnancy, but they exclude the cohort that we looked at for concern that there may be a safety issue.” 

In a third study, researchers at the Rambam Health Care Campus in Haifa, Israel, looked at the effect of physical activity on mode of delivery. The prospective observational analysis included 401 women with singleton pregnancies attempting vaginal deliveries. 

The researchers tracked the number of daily steps taken during gestation using validated phone apps. They adjusted their findings for age, parity, body mass index, and medical and obstetric history. 

The investigators observed a gradual decrease in physical activity as pregnancy progressed (mean of 3184 steps in the first trimester, 2700 steps in mid-pregnancy, and 2152 steps in the third trimester). The overall incidence of cesarean delivery was 10.5%. However, women who were more active during pregnancy had a significantly lower incidence of cesarean delivery. 

Area under the ROC curve, with a cut-off of 2093.5 daily steps, was 0.694 (95% CI, 0.615-0.773), resulting in a significant risk reduction in a 78% reduction in the rate of cesarean surgery (odds ratio, 0.22; 95% CI, 0.104-0.465).

More active patients also had a reduced composite outcome of gestational diabetes, gestational hypertension, and preeclampsia; less use of epidural analgesia during labor; and less postpartum hemorrhage. Preterm birth, labor induction, neonatal weight, and admission to the neonatal intensive care unit were not significantly affected, the researchers reported. 

“Maintaining an active lifestyle during pregnancy should be strongly encouraged,” they wrote. 

The investigators disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

A trio of studies (abstracts 1101, 1079, and 944) presented on February 14 at the meeting sponsored by the Society for Maternal-Fetal Medicine point to the power of staying physically active during pregnancy. The work highlights the beneficial effects of exercise on a variety of outcomes, including depression, anxiety, and reducing the rate of cesarean deliveries.

“Twenty-plus years ago, there were so many recommendations for bed rest in pregnancy,” said Danielle Panelli, MD, a maternal-fetal medicine physician and research scholar at Stanford University in Stanford, California. “We’ve really come full circle on that.” The American College of Obstetricians and Gynecologists recommends pregnant people get at least 150 minutes of moderate activity or 75 minutes of vigorous activity per week. 

Dr. Panelli and colleagues looked at the association of physical activity and anxiety among three groups of pregnant people: 20 outpatients from low-risk obstetric clinics, 20 outpatients from high-risk obstetric clinics, and 19 inpatients. Participants wore accelerometer watches for up to seven days to measure physical activity. The primary outcome was mean daily step count, with secondary outcomes including metabolic equivalent tasks (METs), moderate to vigorous physical activity (MVPA), and anxiety as measured using the State-Trait Anxiety Inventory. 

Low-risk outpatients had an average daily step count of 9090 compared with high-risk outpatients at 8898 and inpatients at 6493. Compared with outpatients, inpatients also had significantly lower METs (adjusted beta, -0.20; 95% CI -0.26 to -0.13; P < .001), and MVPAs (adjusted beta, -43.6; 95% CI, -61.2 to -25.9; P < .001). Over the course of a week, steps progressively decreased for inpatients but not for women in either of the outpatient groups. Among the entire cohort, lower step counts correlated with higher anxiety scores (r = 0.30; P = .02).

“These results highlight the need for physical activity interventions, particularly for hospitalized pregnant people,” Dr. Panelli said. That could be something as simple as asking patients to walk three laps around the unit per day, she suggested.

A second study investigated the effect of physical activity during pregnancy on peripartum depression. Researchers at the University of Alabama at Birmingham reviewed data from participants in nuMoM2b, a large cohort study of pregnant women who would be delivering for the first time and had at least one medical comorbidity, such as chronic hypertension, asthma, or cardiac disease. The investigators looked at activity logs maintained by study participants and turned in at three study visits: 6-13.6 weeks, 14-21.6 weeks, and 22-29.6 weeks. 

Being physically active was associated with 15% lower odds of having an Edinburgh Postnatal Depression Score (EPDS) > 10 (adjusted odds ratio, 0.85; 95% CI, 0.72-0.99). Nine percent of people in the active group and 12% of people in the nonactive group had an EPDS > 10, which is suggestive of depression. However, a change in EPDS from visit one to three and treatment for perinatal depression did not differ by physical activity. 

“One of the interesting findings are that we didn’t see any safety signals [from exercise], so there wasn’t an increase in suspected fetal growth restriction or low fluid or preterm birth, or actual birthweight being low in the people who were active,” said Charlotte McCarley, MD, a maternal-fetal medicine fellow at the University of Alabama at Birmingham, who led the research. “A lot of studies have been done that have looked at prospective exercise in pregnancy, but they exclude the cohort that we looked at for concern that there may be a safety issue.” 

In a third study, researchers at the Rambam Health Care Campus in Haifa, Israel, looked at the effect of physical activity on mode of delivery. The prospective observational analysis included 401 women with singleton pregnancies attempting vaginal deliveries. 

The researchers tracked the number of daily steps taken during gestation using validated phone apps. They adjusted their findings for age, parity, body mass index, and medical and obstetric history. 

The investigators observed a gradual decrease in physical activity as pregnancy progressed (mean of 3184 steps in the first trimester, 2700 steps in mid-pregnancy, and 2152 steps in the third trimester). The overall incidence of cesarean delivery was 10.5%. However, women who were more active during pregnancy had a significantly lower incidence of cesarean delivery. 

Area under the ROC curve, with a cut-off of 2093.5 daily steps, was 0.694 (95% CI, 0.615-0.773), resulting in a significant risk reduction in a 78% reduction in the rate of cesarean surgery (odds ratio, 0.22; 95% CI, 0.104-0.465).

More active patients also had a reduced composite outcome of gestational diabetes, gestational hypertension, and preeclampsia; less use of epidural analgesia during labor; and less postpartum hemorrhage. Preterm birth, labor induction, neonatal weight, and admission to the neonatal intensive care unit were not significantly affected, the researchers reported. 

“Maintaining an active lifestyle during pregnancy should be strongly encouraged,” they wrote. 

The investigators disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

A Pennsylvania urologist is suing his former employer for the alleged illegal enforcement of a noncompete agreement that limits his ability to practice locally for the next 2 years. 

The lawsuit brings renewed attention to the ongoing public discourse around restrictive covenants for physicians as more state and federal legislators signal plans to limit or ban the practice. 

According to a civil suit filed on January 30 in the Court of Common Pleas, Scranton, Pennsylvania, Eric Rottenberg, MD, signed a 3-year employment agreement with Commonwealth Health Physician Network (CPN) in November 2022. He worked for the health system from May to November 2023, seeing patients at several of its locations, including Wilkes-Barre General Hospital and other facilities throughout northeast and central Pennsylvania. 

Although Dr. Rottenberg previously practiced in Albany, New York, court records state he did not bring a significant referral or patient base to the new role, receive any specialized training, or have knowledge of CPN’s trade secrets during his tenure. 

Instead, he was a “9-to-5 practitioner,” or a physician-employee like a “locum tenens whose replacement would not cost the employer more than his traditional compensation,” the complaint said. Dr. Rottenberg only treated patients assigned to him by CPN and its parent company, Commonwealth Health Systems, and did not take a patient base with him upon his departure from CPN. 

Commonwealth Health spokesperson Annmarie Poslock declined to comment on pending litigation. 

After becoming frustrated by “restrictions on his ability to practice medicine” at CPN, Dr. Rottenberg submitted the required 90-day written notice to terminate the employment agreement. He subsequently received a letter from Simon Ratliff, CPN’s chief executive officer, confirming that his last day of employment would be February 11, 2024. Ratliff also reiterated that the noncompete clause would be enforced, essentially banning Dr. Rottenberg from practicing within a 20-mile radius of his previous CPN locations for the next 2 years, court documents said. 

Dr. Rottenberg was recruited by Lehigh Valley Physician Group (LVPG), part of Lehigh Valley Health Network, in December 2023 for a urology position at its Dickson City and Scranton locations — some of which are within 20 miles of CPN facilities, the complaint said. 

Employers often include noncompete terms in physician contracts because they want to keep the departing physician’s patients from following them to a competitor. However, about a dozen states and the District of Columbia have passed legislation that allows physicians and other clinicians to more easily exit contracts and change jobs. 

For example, an Indiana law took effect on July 1 that prohibits employers from entering a noncompete agreement with primary care physicians. Minnesota legislators also banned new noncompete agreements for all employees effective July 1. 

“There’s actually been a long-standing push for bans on physician noncompetes going back to some of the first states to pass them, like Colorado, Delaware, and Massachusetts, in the late 1970s and early 1980s,” said Evan Starr, PhD, associate professor of management and organization at the Robert H. Smith School of Business at the University of Maryland. 

Although New York Governor Kathy Hochul recently vetoed a bill that would have outlawed restrictive covenants, more states may consider passing laws that limit or ban noncompetes amid increasing patient equity and care access concerns. Dr. Starr told this news organization that one reason to eliminate restrictive covenants is because they can cause “third-party harm” to patients. “The patient doesn’t get the choice to sign a noncompete, but they’re going to be impacted by that agreement if the physician has to leave the area,” he said. 

Interestingly, one profession — lawyers — is the only occupation in the US for which noncompete agreements are banned, says Dr. Starr. “Basically, the American Medical Association (AMA) and other physician governing bodies haven’t made the same policies to exempt themselves that the lawyers have.”

That may be changing. In June, the AMA’s House of Delegates adopted policies to support the prohibition of noncompete contracts for employed physicians. The change came several months after the Federal Trade Commission (FTC) proposed a new rule that could more broadly ban companies from enforcing noncompete clauses. 

Despite Rottenberg’s attorney, Ryan Campbell, Esq, claiming that the noncompete is unenforceable without a protectable business interest, CPN would not release him from the agreement and opted to move forward with litigation, court records said. The suit cites several other cases where Pennsylvania judges have released physicians from similar restrictive covenants. 

Mr. Campbell told this news organization that he and his client are “working diligently with CPN and its counsel to resolve the matter amicably and without further litigation.” 

As employers await the FTC’s final rule, Dr. Starr says they could take steps to eliminate noncompete agreements altogether in favor of other stipulations. Contract terms prohibiting physicians from soliciting former patients could protect business interests and still allow patients to seek their preferred physician on their own accord. 
 

A version of this article appeared on Medscape.com .

A Pennsylvania urologist is suing his former employer for the alleged illegal enforcement of a noncompete agreement that limits his ability to practice locally for the next 2 years. 

The lawsuit brings renewed attention to the ongoing public discourse around restrictive covenants for physicians as more state and federal legislators signal plans to limit or ban the practice. 

According to a civil suit filed on January 30 in the Court of Common Pleas, Scranton, Pennsylvania, Eric Rottenberg, MD, signed a 3-year employment agreement with Commonwealth Health Physician Network (CPN) in November 2022. He worked for the health system from May to November 2023, seeing patients at several of its locations, including Wilkes-Barre General Hospital and other facilities throughout northeast and central Pennsylvania. 

Although Dr. Rottenberg previously practiced in Albany, New York, court records state he did not bring a significant referral or patient base to the new role, receive any specialized training, or have knowledge of CPN’s trade secrets during his tenure. 

Instead, he was a “9-to-5 practitioner,” or a physician-employee like a “locum tenens whose replacement would not cost the employer more than his traditional compensation,” the complaint said. Dr. Rottenberg only treated patients assigned to him by CPN and its parent company, Commonwealth Health Systems, and did not take a patient base with him upon his departure from CPN. 

Commonwealth Health spokesperson Annmarie Poslock declined to comment on pending litigation. 

After becoming frustrated by “restrictions on his ability to practice medicine” at CPN, Dr. Rottenberg submitted the required 90-day written notice to terminate the employment agreement. He subsequently received a letter from Simon Ratliff, CPN’s chief executive officer, confirming that his last day of employment would be February 11, 2024. Ratliff also reiterated that the noncompete clause would be enforced, essentially banning Dr. Rottenberg from practicing within a 20-mile radius of his previous CPN locations for the next 2 years, court documents said. 

Dr. Rottenberg was recruited by Lehigh Valley Physician Group (LVPG), part of Lehigh Valley Health Network, in December 2023 for a urology position at its Dickson City and Scranton locations — some of which are within 20 miles of CPN facilities, the complaint said. 

Employers often include noncompete terms in physician contracts because they want to keep the departing physician’s patients from following them to a competitor. However, about a dozen states and the District of Columbia have passed legislation that allows physicians and other clinicians to more easily exit contracts and change jobs. 

For example, an Indiana law took effect on July 1 that prohibits employers from entering a noncompete agreement with primary care physicians. Minnesota legislators also banned new noncompete agreements for all employees effective July 1. 

“There’s actually been a long-standing push for bans on physician noncompetes going back to some of the first states to pass them, like Colorado, Delaware, and Massachusetts, in the late 1970s and early 1980s,” said Evan Starr, PhD, associate professor of management and organization at the Robert H. Smith School of Business at the University of Maryland. 

Although New York Governor Kathy Hochul recently vetoed a bill that would have outlawed restrictive covenants, more states may consider passing laws that limit or ban noncompetes amid increasing patient equity and care access concerns. Dr. Starr told this news organization that one reason to eliminate restrictive covenants is because they can cause “third-party harm” to patients. “The patient doesn’t get the choice to sign a noncompete, but they’re going to be impacted by that agreement if the physician has to leave the area,” he said. 

Interestingly, one profession — lawyers — is the only occupation in the US for which noncompete agreements are banned, says Dr. Starr. “Basically, the American Medical Association (AMA) and other physician governing bodies haven’t made the same policies to exempt themselves that the lawyers have.”

That may be changing. In June, the AMA’s House of Delegates adopted policies to support the prohibition of noncompete contracts for employed physicians. The change came several months after the Federal Trade Commission (FTC) proposed a new rule that could more broadly ban companies from enforcing noncompete clauses. 

Despite Rottenberg’s attorney, Ryan Campbell, Esq, claiming that the noncompete is unenforceable without a protectable business interest, CPN would not release him from the agreement and opted to move forward with litigation, court records said. The suit cites several other cases where Pennsylvania judges have released physicians from similar restrictive covenants. 

Mr. Campbell told this news organization that he and his client are “working diligently with CPN and its counsel to resolve the matter amicably and without further litigation.” 

As employers await the FTC’s final rule, Dr. Starr says they could take steps to eliminate noncompete agreements altogether in favor of other stipulations. Contract terms prohibiting physicians from soliciting former patients could protect business interests and still allow patients to seek their preferred physician on their own accord. 
 

A version of this article appeared on Medscape.com .

A Pennsylvania urologist is suing his former employer for the alleged illegal enforcement of a noncompete agreement that limits his ability to practice locally for the next 2 years. 

The lawsuit brings renewed attention to the ongoing public discourse around restrictive covenants for physicians as more state and federal legislators signal plans to limit or ban the practice. 

According to a civil suit filed on January 30 in the Court of Common Pleas, Scranton, Pennsylvania, Eric Rottenberg, MD, signed a 3-year employment agreement with Commonwealth Health Physician Network (CPN) in November 2022. He worked for the health system from May to November 2023, seeing patients at several of its locations, including Wilkes-Barre General Hospital and other facilities throughout northeast and central Pennsylvania. 

Although Dr. Rottenberg previously practiced in Albany, New York, court records state he did not bring a significant referral or patient base to the new role, receive any specialized training, or have knowledge of CPN’s trade secrets during his tenure. 

Instead, he was a “9-to-5 practitioner,” or a physician-employee like a “locum tenens whose replacement would not cost the employer more than his traditional compensation,” the complaint said. Dr. Rottenberg only treated patients assigned to him by CPN and its parent company, Commonwealth Health Systems, and did not take a patient base with him upon his departure from CPN. 

Commonwealth Health spokesperson Annmarie Poslock declined to comment on pending litigation. 

After becoming frustrated by “restrictions on his ability to practice medicine” at CPN, Dr. Rottenberg submitted the required 90-day written notice to terminate the employment agreement. He subsequently received a letter from Simon Ratliff, CPN’s chief executive officer, confirming that his last day of employment would be February 11, 2024. Ratliff also reiterated that the noncompete clause would be enforced, essentially banning Dr. Rottenberg from practicing within a 20-mile radius of his previous CPN locations for the next 2 years, court documents said. 

Dr. Rottenberg was recruited by Lehigh Valley Physician Group (LVPG), part of Lehigh Valley Health Network, in December 2023 for a urology position at its Dickson City and Scranton locations — some of which are within 20 miles of CPN facilities, the complaint said. 

Employers often include noncompete terms in physician contracts because they want to keep the departing physician’s patients from following them to a competitor. However, about a dozen states and the District of Columbia have passed legislation that allows physicians and other clinicians to more easily exit contracts and change jobs. 

For example, an Indiana law took effect on July 1 that prohibits employers from entering a noncompete agreement with primary care physicians. Minnesota legislators also banned new noncompete agreements for all employees effective July 1. 

“There’s actually been a long-standing push for bans on physician noncompetes going back to some of the first states to pass them, like Colorado, Delaware, and Massachusetts, in the late 1970s and early 1980s,” said Evan Starr, PhD, associate professor of management and organization at the Robert H. Smith School of Business at the University of Maryland. 

Although New York Governor Kathy Hochul recently vetoed a bill that would have outlawed restrictive covenants, more states may consider passing laws that limit or ban noncompetes amid increasing patient equity and care access concerns. Dr. Starr told this news organization that one reason to eliminate restrictive covenants is because they can cause “third-party harm” to patients. “The patient doesn’t get the choice to sign a noncompete, but they’re going to be impacted by that agreement if the physician has to leave the area,” he said. 

Interestingly, one profession — lawyers — is the only occupation in the US for which noncompete agreements are banned, says Dr. Starr. “Basically, the American Medical Association (AMA) and other physician governing bodies haven’t made the same policies to exempt themselves that the lawyers have.”

That may be changing. In June, the AMA’s House of Delegates adopted policies to support the prohibition of noncompete contracts for employed physicians. The change came several months after the Federal Trade Commission (FTC) proposed a new rule that could more broadly ban companies from enforcing noncompete clauses. 

Despite Rottenberg’s attorney, Ryan Campbell, Esq, claiming that the noncompete is unenforceable without a protectable business interest, CPN would not release him from the agreement and opted to move forward with litigation, court records said. The suit cites several other cases where Pennsylvania judges have released physicians from similar restrictive covenants. 

Mr. Campbell told this news organization that he and his client are “working diligently with CPN and its counsel to resolve the matter amicably and without further litigation.” 

As employers await the FTC’s final rule, Dr. Starr says they could take steps to eliminate noncompete agreements altogether in favor of other stipulations. Contract terms prohibiting physicians from soliciting former patients could protect business interests and still allow patients to seek their preferred physician on their own accord. 
 

A version of this article appeared on Medscape.com .

A Nepali medical graduate has filed a federal lawsuit against the National Board of Medical Examiners (NBME), which invalidated her test results earlier this year in response to a widespread cheating scandal. 

Latika Giri, MBBS, of Kathmandu, claims the board violated its own procedures by invalidating exam scores before giving examinees a chance to argue and appeal, according to documents filed on February 12 in the US District Court for the District of Columbia. Dr. Giri alleges that the NBME’s actions were discriminatory against Nepali doctors and run afoul of the Civil Rights Act. 

Dr. Giri is requesting that the court block NBME from invalidating her scores while the lawsuit continues and restore her original results. The complaint was filed as a class action suit on behalf of Dr. Giri and other as yet unnamed plaintiffs affected by the board’s action. 

The lawsuit stems from a January 31 statement from the United States Medical Licensing Examination (USMLE) program that it was voiding scores attained by some examinees after an investigation revealed a pattern of anomalous exam performance associated with test-takers from Nepal. 

The announcement came just before the report about the selling and buying of USMLE questions online, and concerns that cheating on the exam had become “rampant” in recent years. The article was cited in Dr. Giri’s lawsuit.

A spokesman for the NBME said the board does not comment on pending litigation. 

Kritika Tara Deb, a Washington, DC–based attorney representing Dr. Giri, declined to answer specific questions about the case but expressed confidence in the outcome of the suit. 

“A policy that explicitly denies employment to an entire nationality or ethnicity is counter to US law and the USMLE’s non-discrimination principles,” Deb told this news organization in an email. “Such a blatantly discriminatory policy severely punishes honest doctors while unfairly maligning an entire nationality, and we’re confident it will not stand.”
 

Doctor Says She Didn’t Cheat

Dr. Giri is one of 22,000 foreign medical school graduates who complete the USMLE each year, in addition to the 24,000 US medical school graduates who take the exam. 

A 2022 graduate of the Kathmandu University School of Medical Sciences, Dr. Giri completed her board exams in 2023. According to her lawsuit, she studied hard and did not cheat, passing Step 1 and scoring a 252 on Step 2 and a 229 on Step 3. Dr. Giri took Step 1 in Nepal, Step 2 in India, and Step 3 in Connecticut, according to court documents. In January 2024, Dr. Giri was preparing to enter the residency match pool and hoping to start her training in the summer when she received an email from NBME saying her USMLE scores had been invalidated. She was accused of “extremely improbable answer similarity with other examinees testing on the same form at similar times, unusually high performance, and abnormal question response times,” according to the complaint.

Dr. Giri and other examinees affected by the invalidations were given until February 16 to choose from three options. They could request that NBME reconsider its decision, which could take up to 10 weeks; agree to retake the test; or do nothing, in which case their scores would remain invalid and their access to USMLE would be suspended for 3 years. 

If examinees chose options 1 or 2, they would be required to waive their right to sue NBME, according to Dr. Giri’s lawsuit. 

“Because of the schedule of medical-residency matching, all three options result in graduates being unable to practice medicine for at least a year,” attorneys for Dr. Giri wrote in the complaint. “All three options force many people to abruptly leave the country within 30 days and cause every affected person to lose their jobs or the opportunity to seek a job.”
 

Lawsuit: Board Did Not Follow Published Practices

Dr. Giri contends that NBME’s handling of the suspected cheating violates its own published procedures and treats the subset of Nepali examinees differently from other medical graduates. Examinees suspected of cheating are typically first advised of the matter, given an opportunity to share relevant information, and provided the right to appeal, according to the suit. During the process, the test-taker’s score is treated as valid. 

Dr. Giri and others were not provided this same treatment and had their scores invalidated on “the explicit basis that they were associated with Nepal,” the suit claims. The actions are in direct violation of the Civil Rights Act of 1964, which forbids discrimination against “any individual with respect to his terms, conditions, or privileges of employment, because of such individual’s race, color, religion, sex, or national origin,” according to the complaint. 

About 800 people are in the subset of Nepali test-takers targeted by the NBME, according to the suit. 

Dr. Giri said the score invalidations will cause plaintiffs “irreparable harm” if the NBME’s actions are not promptly halted. 

“As of January 31, 2024, plaintiffs who are applying to medical residencies are all ineligible for the Match, the deadline for which is February 28, 2024,” attorneys for Dr. Giri wrote. “All plaintiffs will thus miss this year’s Match no matter what. And NBME has offered no explanation for why it waited until the day before the Match opened to abruptly suspended plaintiffs’ scores: Dr. Giri and many others took some of the invalidated exams more than a year ago.”

Dr. Giri is requesting a decision by the court by February 21. The NBME meanwhile, plans to issue a legal response by February 19, according to court documents. 

Meanwhile, a petition started on change.org by a US emergency physician born calls for the USMLE program to degeneralize the wording of its January 31 statement. The USMLE statement “casts a shadow over the achievement of a supermajority of physicians from Nepal who succeeded through perseverance, honesty, and intelligence,” according to the petition. Petitioners want the USMLE program to change and clarify that it does “not mean to malign physicians from the entire country of Nepal.” More than 2700 people have signed the petition.

A version of this article appeared on Medscape.com.

A Nepali medical graduate has filed a federal lawsuit against the National Board of Medical Examiners (NBME), which invalidated her test results earlier this year in response to a widespread cheating scandal. 

Latika Giri, MBBS, of Kathmandu, claims the board violated its own procedures by invalidating exam scores before giving examinees a chance to argue and appeal, according to documents filed on February 12 in the US District Court for the District of Columbia. Dr. Giri alleges that the NBME’s actions were discriminatory against Nepali doctors and run afoul of the Civil Rights Act. 

Dr. Giri is requesting that the court block NBME from invalidating her scores while the lawsuit continues and restore her original results. The complaint was filed as a class action suit on behalf of Dr. Giri and other as yet unnamed plaintiffs affected by the board’s action. 

The lawsuit stems from a January 31 statement from the United States Medical Licensing Examination (USMLE) program that it was voiding scores attained by some examinees after an investigation revealed a pattern of anomalous exam performance associated with test-takers from Nepal. 

The announcement came just before the report about the selling and buying of USMLE questions online, and concerns that cheating on the exam had become “rampant” in recent years. The article was cited in Dr. Giri’s lawsuit.

A spokesman for the NBME said the board does not comment on pending litigation. 

Kritika Tara Deb, a Washington, DC–based attorney representing Dr. Giri, declined to answer specific questions about the case but expressed confidence in the outcome of the suit. 

“A policy that explicitly denies employment to an entire nationality or ethnicity is counter to US law and the USMLE’s non-discrimination principles,” Deb told this news organization in an email. “Such a blatantly discriminatory policy severely punishes honest doctors while unfairly maligning an entire nationality, and we’re confident it will not stand.”
 

Doctor Says She Didn’t Cheat

Dr. Giri is one of 22,000 foreign medical school graduates who complete the USMLE each year, in addition to the 24,000 US medical school graduates who take the exam. 

A 2022 graduate of the Kathmandu University School of Medical Sciences, Dr. Giri completed her board exams in 2023. According to her lawsuit, she studied hard and did not cheat, passing Step 1 and scoring a 252 on Step 2 and a 229 on Step 3. Dr. Giri took Step 1 in Nepal, Step 2 in India, and Step 3 in Connecticut, according to court documents. In January 2024, Dr. Giri was preparing to enter the residency match pool and hoping to start her training in the summer when she received an email from NBME saying her USMLE scores had been invalidated. She was accused of “extremely improbable answer similarity with other examinees testing on the same form at similar times, unusually high performance, and abnormal question response times,” according to the complaint.

Dr. Giri and other examinees affected by the invalidations were given until February 16 to choose from three options. They could request that NBME reconsider its decision, which could take up to 10 weeks; agree to retake the test; or do nothing, in which case their scores would remain invalid and their access to USMLE would be suspended for 3 years. 

If examinees chose options 1 or 2, they would be required to waive their right to sue NBME, according to Dr. Giri’s lawsuit. 

“Because of the schedule of medical-residency matching, all three options result in graduates being unable to practice medicine for at least a year,” attorneys for Dr. Giri wrote in the complaint. “All three options force many people to abruptly leave the country within 30 days and cause every affected person to lose their jobs or the opportunity to seek a job.”
 

Lawsuit: Board Did Not Follow Published Practices

Dr. Giri contends that NBME’s handling of the suspected cheating violates its own published procedures and treats the subset of Nepali examinees differently from other medical graduates. Examinees suspected of cheating are typically first advised of the matter, given an opportunity to share relevant information, and provided the right to appeal, according to the suit. During the process, the test-taker’s score is treated as valid. 

Dr. Giri and others were not provided this same treatment and had their scores invalidated on “the explicit basis that they were associated with Nepal,” the suit claims. The actions are in direct violation of the Civil Rights Act of 1964, which forbids discrimination against “any individual with respect to his terms, conditions, or privileges of employment, because of such individual’s race, color, religion, sex, or national origin,” according to the complaint. 

About 800 people are in the subset of Nepali test-takers targeted by the NBME, according to the suit. 

Dr. Giri said the score invalidations will cause plaintiffs “irreparable harm” if the NBME’s actions are not promptly halted. 

“As of January 31, 2024, plaintiffs who are applying to medical residencies are all ineligible for the Match, the deadline for which is February 28, 2024,” attorneys for Dr. Giri wrote. “All plaintiffs will thus miss this year’s Match no matter what. And NBME has offered no explanation for why it waited until the day before the Match opened to abruptly suspended plaintiffs’ scores: Dr. Giri and many others took some of the invalidated exams more than a year ago.”

Dr. Giri is requesting a decision by the court by February 21. The NBME meanwhile, plans to issue a legal response by February 19, according to court documents. 

Meanwhile, a petition started on change.org by a US emergency physician born calls for the USMLE program to degeneralize the wording of its January 31 statement. The USMLE statement “casts a shadow over the achievement of a supermajority of physicians from Nepal who succeeded through perseverance, honesty, and intelligence,” according to the petition. Petitioners want the USMLE program to change and clarify that it does “not mean to malign physicians from the entire country of Nepal.” More than 2700 people have signed the petition.

A version of this article appeared on Medscape.com.

A Nepali medical graduate has filed a federal lawsuit against the National Board of Medical Examiners (NBME), which invalidated her test results earlier this year in response to a widespread cheating scandal. 

Latika Giri, MBBS, of Kathmandu, claims the board violated its own procedures by invalidating exam scores before giving examinees a chance to argue and appeal, according to documents filed on February 12 in the US District Court for the District of Columbia. Dr. Giri alleges that the NBME’s actions were discriminatory against Nepali doctors and run afoul of the Civil Rights Act. 

Dr. Giri is requesting that the court block NBME from invalidating her scores while the lawsuit continues and restore her original results. The complaint was filed as a class action suit on behalf of Dr. Giri and other as yet unnamed plaintiffs affected by the board’s action. 

The lawsuit stems from a January 31 statement from the United States Medical Licensing Examination (USMLE) program that it was voiding scores attained by some examinees after an investigation revealed a pattern of anomalous exam performance associated with test-takers from Nepal. 

The announcement came just before the report about the selling and buying of USMLE questions online, and concerns that cheating on the exam had become “rampant” in recent years. The article was cited in Dr. Giri’s lawsuit.

A spokesman for the NBME said the board does not comment on pending litigation. 

Kritika Tara Deb, a Washington, DC–based attorney representing Dr. Giri, declined to answer specific questions about the case but expressed confidence in the outcome of the suit. 

“A policy that explicitly denies employment to an entire nationality or ethnicity is counter to US law and the USMLE’s non-discrimination principles,” Deb told this news organization in an email. “Such a blatantly discriminatory policy severely punishes honest doctors while unfairly maligning an entire nationality, and we’re confident it will not stand.”
 

Doctor Says She Didn’t Cheat

Dr. Giri is one of 22,000 foreign medical school graduates who complete the USMLE each year, in addition to the 24,000 US medical school graduates who take the exam. 

A 2022 graduate of the Kathmandu University School of Medical Sciences, Dr. Giri completed her board exams in 2023. According to her lawsuit, she studied hard and did not cheat, passing Step 1 and scoring a 252 on Step 2 and a 229 on Step 3. Dr. Giri took Step 1 in Nepal, Step 2 in India, and Step 3 in Connecticut, according to court documents. In January 2024, Dr. Giri was preparing to enter the residency match pool and hoping to start her training in the summer when she received an email from NBME saying her USMLE scores had been invalidated. She was accused of “extremely improbable answer similarity with other examinees testing on the same form at similar times, unusually high performance, and abnormal question response times,” according to the complaint.

Dr. Giri and other examinees affected by the invalidations were given until February 16 to choose from three options. They could request that NBME reconsider its decision, which could take up to 10 weeks; agree to retake the test; or do nothing, in which case their scores would remain invalid and their access to USMLE would be suspended for 3 years. 

If examinees chose options 1 or 2, they would be required to waive their right to sue NBME, according to Dr. Giri’s lawsuit. 

“Because of the schedule of medical-residency matching, all three options result in graduates being unable to practice medicine for at least a year,” attorneys for Dr. Giri wrote in the complaint. “All three options force many people to abruptly leave the country within 30 days and cause every affected person to lose their jobs or the opportunity to seek a job.”
 

Lawsuit: Board Did Not Follow Published Practices

Dr. Giri contends that NBME’s handling of the suspected cheating violates its own published procedures and treats the subset of Nepali examinees differently from other medical graduates. Examinees suspected of cheating are typically first advised of the matter, given an opportunity to share relevant information, and provided the right to appeal, according to the suit. During the process, the test-taker’s score is treated as valid. 

Dr. Giri and others were not provided this same treatment and had their scores invalidated on “the explicit basis that they were associated with Nepal,” the suit claims. The actions are in direct violation of the Civil Rights Act of 1964, which forbids discrimination against “any individual with respect to his terms, conditions, or privileges of employment, because of such individual’s race, color, religion, sex, or national origin,” according to the complaint. 

About 800 people are in the subset of Nepali test-takers targeted by the NBME, according to the suit. 

Dr. Giri said the score invalidations will cause plaintiffs “irreparable harm” if the NBME’s actions are not promptly halted. 

“As of January 31, 2024, plaintiffs who are applying to medical residencies are all ineligible for the Match, the deadline for which is February 28, 2024,” attorneys for Dr. Giri wrote. “All plaintiffs will thus miss this year’s Match no matter what. And NBME has offered no explanation for why it waited until the day before the Match opened to abruptly suspended plaintiffs’ scores: Dr. Giri and many others took some of the invalidated exams more than a year ago.”

Dr. Giri is requesting a decision by the court by February 21. The NBME meanwhile, plans to issue a legal response by February 19, according to court documents. 

Meanwhile, a petition started on change.org by a US emergency physician born calls for the USMLE program to degeneralize the wording of its January 31 statement. The USMLE statement “casts a shadow over the achievement of a supermajority of physicians from Nepal who succeeded through perseverance, honesty, and intelligence,” according to the petition. Petitioners want the USMLE program to change and clarify that it does “not mean to malign physicians from the entire country of Nepal.” More than 2700 people have signed the petition.

A version of this article appeared on Medscape.com.

I recently received an email from a distraught physician. Several months previously, he had sold his practice to a large private equity-funded group. The terms spelled out in the group’s letter of intent (LOI) seemed ideal. He could continue running his office any way he wished, set his own hours and fees, and keep his employees. All his overhead expenses would disappear. His income would remain the same, maybe even increase. He signed it eagerly.

When he received the actual sale and employment contracts, none of the details promised in the LOI were included; but he figured that since they were spelled out in the LOI, which both he and the buyer had signed, he was covered. His attorney — a family friend with no experience in medical practice transactions — approved the documents.

The deal seemed too good to be true, and it was. The day after the sale closed, all his employees received termination notices. The group offered to rehire some of them, but at lower salaries and reduced benefits. (Most declined.) The new staffers he received were inadequately trained and unfamiliar with his standard office procedures. Patients complained that fees had increased substantially. His own compensation was contingent on meeting strict billing and performance goals. Malpractice premiums remained his responsibility. His office hours were lengthened to include evenings and Saturday mornings.

When he complained to the group that none of the things promised in the LOI had been delivered, he was informed that the LOI was not legally binding. In fact, the sale and employment contracts both clearly specified that they “replaced any previous written or oral agreements between the parties.”

There are some valuable lessons to be learned here. First, whether you are a young physician seeking a new job with a hospital or large practice, or an older one looking to sell an established practice, retain an attorney experienced in medical transactions early, before you sign anything, binding or not. Second, recognize that any promises made in an LOI must be spelled out in the employment and/or sale contract as well.

You might ask, if the terms in an LOI are not binding, why bother with one at all? For one thing, you want to make sure that you and your potential employer or buyer are on the same page with respect to major terms before you get down to details in the employment agreement and/or the medical practice sale agreement. For another, in most states certain LOI provisions are legally binding. For example, the document will most likely provide that each party is responsible for its own attorneys’ fees and for maintaining confidentiality during the negotiations, and that you will not negotiate with any other parties for some specified period of time. In most cases, such provisions are binding whether you go on to sign a formal contract or not.

When you receive an LOI, go through it carefully and identify areas of concern. The offering party will likely be in a rush to sign you up; but once you sign, you won’t be able to negotiate with anyone else for a while, which weakens your negotiating position. Regardless of what is said about time being “of the essence,” proceed slowly and with caution.

Bear in mind that employers and buyers never begin with their best offer. Unless you have been through this before, it is unlikely that you will know your value as an employee or the value of your practice, or what exactly you are entitled to ask for. Rather than signing something you don’t completely understand, explain to the offering party that you need time to consider and evaluate their offer.

This is the time to hire a competent medical attorney to do some due diligence on the offering party and review their offer, and to educate yourself about practice value and compensation benchmarks in your area. You and your counsel should assemble a list of things that you want changed in the LOI, then present them to the other side. They should be amenable to negotiation. If they are not (as was the case in the example presented earlier), you should reconsider whether you really want to be associated with that particular buyer or employer.

Once you have signed the LOI, experts say speed then works to your advantage. “Time kills all deals,” as one lawyer put it. “The longer it takes to close the transaction, the more that can go wrong.” The prospective employer or buyer could uncover information about you or your practice that decreases their perception of value, or economic conditions might change.

While speed is now important, and most of the core issues should already have been resolved in the LOI, don’t be afraid to ask for everything you want, whether it’s a better sale price, higher compensation, a favorable call schedule, more vacation time, or anything else. You won’t know what you can get if you don’t ask for it.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

I recently received an email from a distraught physician. Several months previously, he had sold his practice to a large private equity-funded group. The terms spelled out in the group’s letter of intent (LOI) seemed ideal. He could continue running his office any way he wished, set his own hours and fees, and keep his employees. All his overhead expenses would disappear. His income would remain the same, maybe even increase. He signed it eagerly.

When he received the actual sale and employment contracts, none of the details promised in the LOI were included; but he figured that since they were spelled out in the LOI, which both he and the buyer had signed, he was covered. His attorney — a family friend with no experience in medical practice transactions — approved the documents.

The deal seemed too good to be true, and it was. The day after the sale closed, all his employees received termination notices. The group offered to rehire some of them, but at lower salaries and reduced benefits. (Most declined.) The new staffers he received were inadequately trained and unfamiliar with his standard office procedures. Patients complained that fees had increased substantially. His own compensation was contingent on meeting strict billing and performance goals. Malpractice premiums remained his responsibility. His office hours were lengthened to include evenings and Saturday mornings.

When he complained to the group that none of the things promised in the LOI had been delivered, he was informed that the LOI was not legally binding. In fact, the sale and employment contracts both clearly specified that they “replaced any previous written or oral agreements between the parties.”

There are some valuable lessons to be learned here. First, whether you are a young physician seeking a new job with a hospital or large practice, or an older one looking to sell an established practice, retain an attorney experienced in medical transactions early, before you sign anything, binding or not. Second, recognize that any promises made in an LOI must be spelled out in the employment and/or sale contract as well.

You might ask, if the terms in an LOI are not binding, why bother with one at all? For one thing, you want to make sure that you and your potential employer or buyer are on the same page with respect to major terms before you get down to details in the employment agreement and/or the medical practice sale agreement. For another, in most states certain LOI provisions are legally binding. For example, the document will most likely provide that each party is responsible for its own attorneys’ fees and for maintaining confidentiality during the negotiations, and that you will not negotiate with any other parties for some specified period of time. In most cases, such provisions are binding whether you go on to sign a formal contract or not.

When you receive an LOI, go through it carefully and identify areas of concern. The offering party will likely be in a rush to sign you up; but once you sign, you won’t be able to negotiate with anyone else for a while, which weakens your negotiating position. Regardless of what is said about time being “of the essence,” proceed slowly and with caution.

Bear in mind that employers and buyers never begin with their best offer. Unless you have been through this before, it is unlikely that you will know your value as an employee or the value of your practice, or what exactly you are entitled to ask for. Rather than signing something you don’t completely understand, explain to the offering party that you need time to consider and evaluate their offer.

This is the time to hire a competent medical attorney to do some due diligence on the offering party and review their offer, and to educate yourself about practice value and compensation benchmarks in your area. You and your counsel should assemble a list of things that you want changed in the LOI, then present them to the other side. They should be amenable to negotiation. If they are not (as was the case in the example presented earlier), you should reconsider whether you really want to be associated with that particular buyer or employer.

Once you have signed the LOI, experts say speed then works to your advantage. “Time kills all deals,” as one lawyer put it. “The longer it takes to close the transaction, the more that can go wrong.” The prospective employer or buyer could uncover information about you or your practice that decreases their perception of value, or economic conditions might change.

While speed is now important, and most of the core issues should already have been resolved in the LOI, don’t be afraid to ask for everything you want, whether it’s a better sale price, higher compensation, a favorable call schedule, more vacation time, or anything else. You won’t know what you can get if you don’t ask for it.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

I recently received an email from a distraught physician. Several months previously, he had sold his practice to a large private equity-funded group. The terms spelled out in the group’s letter of intent (LOI) seemed ideal. He could continue running his office any way he wished, set his own hours and fees, and keep his employees. All his overhead expenses would disappear. His income would remain the same, maybe even increase. He signed it eagerly.

When he received the actual sale and employment contracts, none of the details promised in the LOI were included; but he figured that since they were spelled out in the LOI, which both he and the buyer had signed, he was covered. His attorney — a family friend with no experience in medical practice transactions — approved the documents.

The deal seemed too good to be true, and it was. The day after the sale closed, all his employees received termination notices. The group offered to rehire some of them, but at lower salaries and reduced benefits. (Most declined.) The new staffers he received were inadequately trained and unfamiliar with his standard office procedures. Patients complained that fees had increased substantially. His own compensation was contingent on meeting strict billing and performance goals. Malpractice premiums remained his responsibility. His office hours were lengthened to include evenings and Saturday mornings.

When he complained to the group that none of the things promised in the LOI had been delivered, he was informed that the LOI was not legally binding. In fact, the sale and employment contracts both clearly specified that they “replaced any previous written or oral agreements between the parties.”

There are some valuable lessons to be learned here. First, whether you are a young physician seeking a new job with a hospital or large practice, or an older one looking to sell an established practice, retain an attorney experienced in medical transactions early, before you sign anything, binding or not. Second, recognize that any promises made in an LOI must be spelled out in the employment and/or sale contract as well.

You might ask, if the terms in an LOI are not binding, why bother with one at all? For one thing, you want to make sure that you and your potential employer or buyer are on the same page with respect to major terms before you get down to details in the employment agreement and/or the medical practice sale agreement. For another, in most states certain LOI provisions are legally binding. For example, the document will most likely provide that each party is responsible for its own attorneys’ fees and for maintaining confidentiality during the negotiations, and that you will not negotiate with any other parties for some specified period of time. In most cases, such provisions are binding whether you go on to sign a formal contract or not.

When you receive an LOI, go through it carefully and identify areas of concern. The offering party will likely be in a rush to sign you up; but once you sign, you won’t be able to negotiate with anyone else for a while, which weakens your negotiating position. Regardless of what is said about time being “of the essence,” proceed slowly and with caution.

Bear in mind that employers and buyers never begin with their best offer. Unless you have been through this before, it is unlikely that you will know your value as an employee or the value of your practice, or what exactly you are entitled to ask for. Rather than signing something you don’t completely understand, explain to the offering party that you need time to consider and evaluate their offer.

This is the time to hire a competent medical attorney to do some due diligence on the offering party and review their offer, and to educate yourself about practice value and compensation benchmarks in your area. You and your counsel should assemble a list of things that you want changed in the LOI, then present them to the other side. They should be amenable to negotiation. If they are not (as was the case in the example presented earlier), you should reconsider whether you really want to be associated with that particular buyer or employer.

Once you have signed the LOI, experts say speed then works to your advantage. “Time kills all deals,” as one lawyer put it. “The longer it takes to close the transaction, the more that can go wrong.” The prospective employer or buyer could uncover information about you or your practice that decreases their perception of value, or economic conditions might change.

While speed is now important, and most of the core issues should already have been resolved in the LOI, don’t be afraid to ask for everything you want, whether it’s a better sale price, higher compensation, a favorable call schedule, more vacation time, or anything else. You won’t know what you can get if you don’t ask for it.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Several new clinical trials in gynecologic cancers have started enrolling recently. Perhaps one of your patients is eligible to take part?

Persistent or recurrent endometrial cancer or any advanced solid gynecologic tumor with appropriate ATR mutations. Patients with one of these diagnoses may be eligible to join a phase 2, randomized, open-label study of an experimental drug called ART0380. ART0380 inhibits the ability of cancer cells to repair DNA damage by targeting a DNA repair kinase called ATR (ataxia telangiectasia–mutated and Rad3-related) protein, which is faulty in some tumors. The hope is that ART0380 will overwhelm the inadequate DNA repair processes of these cancer cells while sparing the more robust DNA repair in healthy cells. 

All participants in the trial will take daily oral ART0380 until disease progression, withdrawal of consent, or unacceptable toxicity, whichever happens first. Some individuals will receive the treatment for 3 weeks out of every 4. Sites in California, Illinois, Massachusetts, New York, Oklahoma, Pennsylvania, Rhode Island, and France started recruiting 60 participants with endometrial cancer or any solid tumor in September 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and quality of life (QOL) is not assessed. More details at ClinicalTrials.gov

Maurie Markman, MD, president of medicine and science at City of Hope, Atlanta, who is not involved in this trial, explained that because “ a meaningful proportion of this population may have a defect in this DNA repair mechanism,” this hypothesis seems “worthy of clinical exploration.” 

Cancer of the endometrium, cervix, vagina, or vulva. Women with one of these types of cancer who can read and understand English or Spanish can join a randomized, open-label phase 2 trial to determine whether Reiki therapy can reduce pain and distress associated with brachytherapy. 

Reiki is a complementary therapy that involves a Reiki practitioner holding their hands lightly on or above the patient’s body for several minutes. Some hospitals in the US and the UK offer Reiki as a relaxation aid, although high-quality science is lacking.

In this study, one group of participants will each undergo Reiki in a quiet clinic room during the lengthy waiting period between placement of the vaginal cylinder and infusion of the radiation source, which is a time of anxiety and discomfort for many women. A second group of women will simply lie and wait in a clinic room, if desired accompanied by a friend or family member. 

The Huntsman Cancer Institute, Salt Lake City, Utah, started recruiting its 68 participants in October 2023. The primary outcome is self-reported anxiety. The secondary outcomes are other validated measures of anxiety, pain, and depression. Overall survival and broader measures of QOL will not be assessed. More details at ClinicalTrials.gov

Dr. Markman said that the benefits of Reiki may be “nothing more than a placebo effect.” But he highlighted the novelty of conducting a randomized trial to scientifically test Reiki’s “widely applied (without any real evidence) ‘integrative medicine’ approach to symptom management.”

Unresectable or metastatic endometrial cancer with deficient mismatch repair /high microsatellite instability. People in this clinical situation whose disease has progressed after one or two lines of prior chemotherapy, including platinum-based treatment, may be interested in an open-label nonrandomized, phase 2 investigation of bispecific antibody acasunlimab in combination with pembrolizumab (Keytruda). 

Acasunlimab stimulates T-cell antitumor activity as well as blocking programmed death ligand 1 (PD-L1) and is being tested in several types of solid-tumor cancer. For up to 2 years, all participants will receive intravenous (IV) infusions of the drug combination. Study sites in Florida and Europe opened in January 2024, ready for 80 participants. The primary outcome is objective response rate. Overall survival will not be assessed. More details at ClinicalTrials.gov

“In the absence of a randomized population to compare treatment outcomes, the results of this trial will likely provide limited data upon which to determine the clinical benefits of this novel drug combination strategy,” said Dr. Markman. However, he added, “the results will be helpful in assessing the potential toxicity of this approach.”

Recurrent or metastatic endometrial cancer with proficient mismatch repair. Women with this diagnosis who have progressed after one prior platinum chemotherapy regimen in any setting may wish to consider a randomized, triple-blind, phase 2 trial of pembrolizumab plus favezelimab. Favezelimab, which blocks the lymphocyte activation gene 3 (LAG3), appears to boost the antitumor activity of programmed cell death protein 1 (PD-1) inhibition in other cancers such as classic Hodgkin lymphoma. 

In the trial, participants will be assigned to one of four groups. One group will receive 17 doses of the combination treatment IV every 3 weeks — three doses in the neoadjuvant period and 14 as adjuvant therapy. A second group of individuals will receive IV pembrolizumab monotherapy on the same schedule. A third will be given up to 35 doses of the combo therapy every 3 weeks plus a daily capsule of lenvatinib (Lenvima). The fourth group will receive 35 doses of pembrolizumab plus daily lenvatinib. 

Sites in North Carolina, New Jersey, Pennsylvania, and four countries other than the US started recruiting 60 participants with a solid tumor in September 2023. Pathologic complete response and objective response rate are the primary endpoints. Overall survival over approximately 3.5 years is a secondary endpoint, and QOL will not be measured. More details at ClinicalTrials.gov

Unresectable advanced or metastatic HER2-positive endometrial or ovarian cancer. Adults with one of these diagnoses in whom failed platinum-based therapy has failed may enroll in an open-label, phase 2 study to see whether their disease will respond to the antibody-drug conjugate disitamab vedotin. Everyone in the trial will receive IV disitamab vedotin every 2 weeks for up to approximately 5 years. 

Study sites in California, Connecticut, Michigan, Minnesota, Montana, New York, Ohio, Texas, and Canada began welcoming their 190 participants with one of a range of solid cancers in November 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and QOL will not be tracked. More details at ClinicalTrials.gov

High-risk locally advanced cervical cancer. Girls and women older than 14 years with this cancer that has not progressed after platinum-based chemoradiation are sought for a randomized, quadruple-blind, phase 3 trial to determine whether the investigational immunotherapy volrustomig can slow disease progression. Volrustomig targets PD-1 and cytotoxic T lymphocyte protein 4 (CTLA4) and is being tested in a wide range of solid cancers. 

For approximately 3 years or until disease progression or death, whichever happens first, half of participants will receive IV infusions of volrustomig while the others will receive saline. Asian research sites started seeking the study’s 1000 participants in September 2023, while centers in 12 US states and eight other countries are gearing up for patient enrollment. Progression-free survival in participants with PD-L1 expression is the primary endpoint; overall survival and QOL are secondary endpoints. More details at ClinicalTrials.gov

All trial information is from the National Institutes of Health US National Library of Medicine (online at ClinicalTrials.gov). Dr. Markman declared he is not involved with these trials.

A version of this article appeared on Medscape.com .

Several new clinical trials in gynecologic cancers have started enrolling recently. Perhaps one of your patients is eligible to take part?

Persistent or recurrent endometrial cancer or any advanced solid gynecologic tumor with appropriate ATR mutations. Patients with one of these diagnoses may be eligible to join a phase 2, randomized, open-label study of an experimental drug called ART0380. ART0380 inhibits the ability of cancer cells to repair DNA damage by targeting a DNA repair kinase called ATR (ataxia telangiectasia–mutated and Rad3-related) protein, which is faulty in some tumors. The hope is that ART0380 will overwhelm the inadequate DNA repair processes of these cancer cells while sparing the more robust DNA repair in healthy cells. 

All participants in the trial will take daily oral ART0380 until disease progression, withdrawal of consent, or unacceptable toxicity, whichever happens first. Some individuals will receive the treatment for 3 weeks out of every 4. Sites in California, Illinois, Massachusetts, New York, Oklahoma, Pennsylvania, Rhode Island, and France started recruiting 60 participants with endometrial cancer or any solid tumor in September 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and quality of life (QOL) is not assessed. More details at ClinicalTrials.gov

Maurie Markman, MD, president of medicine and science at City of Hope, Atlanta, who is not involved in this trial, explained that because “ a meaningful proportion of this population may have a defect in this DNA repair mechanism,” this hypothesis seems “worthy of clinical exploration.” 

Cancer of the endometrium, cervix, vagina, or vulva. Women with one of these types of cancer who can read and understand English or Spanish can join a randomized, open-label phase 2 trial to determine whether Reiki therapy can reduce pain and distress associated with brachytherapy. 

Reiki is a complementary therapy that involves a Reiki practitioner holding their hands lightly on or above the patient’s body for several minutes. Some hospitals in the US and the UK offer Reiki as a relaxation aid, although high-quality science is lacking.

In this study, one group of participants will each undergo Reiki in a quiet clinic room during the lengthy waiting period between placement of the vaginal cylinder and infusion of the radiation source, which is a time of anxiety and discomfort for many women. A second group of women will simply lie and wait in a clinic room, if desired accompanied by a friend or family member. 

The Huntsman Cancer Institute, Salt Lake City, Utah, started recruiting its 68 participants in October 2023. The primary outcome is self-reported anxiety. The secondary outcomes are other validated measures of anxiety, pain, and depression. Overall survival and broader measures of QOL will not be assessed. More details at ClinicalTrials.gov

Dr. Markman said that the benefits of Reiki may be “nothing more than a placebo effect.” But he highlighted the novelty of conducting a randomized trial to scientifically test Reiki’s “widely applied (without any real evidence) ‘integrative medicine’ approach to symptom management.”

Unresectable or metastatic endometrial cancer with deficient mismatch repair /high microsatellite instability. People in this clinical situation whose disease has progressed after one or two lines of prior chemotherapy, including platinum-based treatment, may be interested in an open-label nonrandomized, phase 2 investigation of bispecific antibody acasunlimab in combination with pembrolizumab (Keytruda). 

Acasunlimab stimulates T-cell antitumor activity as well as blocking programmed death ligand 1 (PD-L1) and is being tested in several types of solid-tumor cancer. For up to 2 years, all participants will receive intravenous (IV) infusions of the drug combination. Study sites in Florida and Europe opened in January 2024, ready for 80 participants. The primary outcome is objective response rate. Overall survival will not be assessed. More details at ClinicalTrials.gov

“In the absence of a randomized population to compare treatment outcomes, the results of this trial will likely provide limited data upon which to determine the clinical benefits of this novel drug combination strategy,” said Dr. Markman. However, he added, “the results will be helpful in assessing the potential toxicity of this approach.”

Recurrent or metastatic endometrial cancer with proficient mismatch repair. Women with this diagnosis who have progressed after one prior platinum chemotherapy regimen in any setting may wish to consider a randomized, triple-blind, phase 2 trial of pembrolizumab plus favezelimab. Favezelimab, which blocks the lymphocyte activation gene 3 (LAG3), appears to boost the antitumor activity of programmed cell death protein 1 (PD-1) inhibition in other cancers such as classic Hodgkin lymphoma. 

In the trial, participants will be assigned to one of four groups. One group will receive 17 doses of the combination treatment IV every 3 weeks — three doses in the neoadjuvant period and 14 as adjuvant therapy. A second group of individuals will receive IV pembrolizumab monotherapy on the same schedule. A third will be given up to 35 doses of the combo therapy every 3 weeks plus a daily capsule of lenvatinib (Lenvima). The fourth group will receive 35 doses of pembrolizumab plus daily lenvatinib. 

Sites in North Carolina, New Jersey, Pennsylvania, and four countries other than the US started recruiting 60 participants with a solid tumor in September 2023. Pathologic complete response and objective response rate are the primary endpoints. Overall survival over approximately 3.5 years is a secondary endpoint, and QOL will not be measured. More details at ClinicalTrials.gov

Unresectable advanced or metastatic HER2-positive endometrial or ovarian cancer. Adults with one of these diagnoses in whom failed platinum-based therapy has failed may enroll in an open-label, phase 2 study to see whether their disease will respond to the antibody-drug conjugate disitamab vedotin. Everyone in the trial will receive IV disitamab vedotin every 2 weeks for up to approximately 5 years. 

Study sites in California, Connecticut, Michigan, Minnesota, Montana, New York, Ohio, Texas, and Canada began welcoming their 190 participants with one of a range of solid cancers in November 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and QOL will not be tracked. More details at ClinicalTrials.gov

High-risk locally advanced cervical cancer. Girls and women older than 14 years with this cancer that has not progressed after platinum-based chemoradiation are sought for a randomized, quadruple-blind, phase 3 trial to determine whether the investigational immunotherapy volrustomig can slow disease progression. Volrustomig targets PD-1 and cytotoxic T lymphocyte protein 4 (CTLA4) and is being tested in a wide range of solid cancers. 

For approximately 3 years or until disease progression or death, whichever happens first, half of participants will receive IV infusions of volrustomig while the others will receive saline. Asian research sites started seeking the study’s 1000 participants in September 2023, while centers in 12 US states and eight other countries are gearing up for patient enrollment. Progression-free survival in participants with PD-L1 expression is the primary endpoint; overall survival and QOL are secondary endpoints. More details at ClinicalTrials.gov

All trial information is from the National Institutes of Health US National Library of Medicine (online at ClinicalTrials.gov). Dr. Markman declared he is not involved with these trials.

A version of this article appeared on Medscape.com .

Several new clinical trials in gynecologic cancers have started enrolling recently. Perhaps one of your patients is eligible to take part?

Persistent or recurrent endometrial cancer or any advanced solid gynecologic tumor with appropriate ATR mutations. Patients with one of these diagnoses may be eligible to join a phase 2, randomized, open-label study of an experimental drug called ART0380. ART0380 inhibits the ability of cancer cells to repair DNA damage by targeting a DNA repair kinase called ATR (ataxia telangiectasia–mutated and Rad3-related) protein, which is faulty in some tumors. The hope is that ART0380 will overwhelm the inadequate DNA repair processes of these cancer cells while sparing the more robust DNA repair in healthy cells. 

All participants in the trial will take daily oral ART0380 until disease progression, withdrawal of consent, or unacceptable toxicity, whichever happens first. Some individuals will receive the treatment for 3 weeks out of every 4. Sites in California, Illinois, Massachusetts, New York, Oklahoma, Pennsylvania, Rhode Island, and France started recruiting 60 participants with endometrial cancer or any solid tumor in September 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and quality of life (QOL) is not assessed. More details at ClinicalTrials.gov

Maurie Markman, MD, president of medicine and science at City of Hope, Atlanta, who is not involved in this trial, explained that because “ a meaningful proportion of this population may have a defect in this DNA repair mechanism,” this hypothesis seems “worthy of clinical exploration.” 

Cancer of the endometrium, cervix, vagina, or vulva. Women with one of these types of cancer who can read and understand English or Spanish can join a randomized, open-label phase 2 trial to determine whether Reiki therapy can reduce pain and distress associated with brachytherapy. 

Reiki is a complementary therapy that involves a Reiki practitioner holding their hands lightly on or above the patient’s body for several minutes. Some hospitals in the US and the UK offer Reiki as a relaxation aid, although high-quality science is lacking.

In this study, one group of participants will each undergo Reiki in a quiet clinic room during the lengthy waiting period between placement of the vaginal cylinder and infusion of the radiation source, which is a time of anxiety and discomfort for many women. A second group of women will simply lie and wait in a clinic room, if desired accompanied by a friend or family member. 

The Huntsman Cancer Institute, Salt Lake City, Utah, started recruiting its 68 participants in October 2023. The primary outcome is self-reported anxiety. The secondary outcomes are other validated measures of anxiety, pain, and depression. Overall survival and broader measures of QOL will not be assessed. More details at ClinicalTrials.gov

Dr. Markman said that the benefits of Reiki may be “nothing more than a placebo effect.” But he highlighted the novelty of conducting a randomized trial to scientifically test Reiki’s “widely applied (without any real evidence) ‘integrative medicine’ approach to symptom management.”

Unresectable or metastatic endometrial cancer with deficient mismatch repair /high microsatellite instability. People in this clinical situation whose disease has progressed after one or two lines of prior chemotherapy, including platinum-based treatment, may be interested in an open-label nonrandomized, phase 2 investigation of bispecific antibody acasunlimab in combination with pembrolizumab (Keytruda). 

Acasunlimab stimulates T-cell antitumor activity as well as blocking programmed death ligand 1 (PD-L1) and is being tested in several types of solid-tumor cancer. For up to 2 years, all participants will receive intravenous (IV) infusions of the drug combination. Study sites in Florida and Europe opened in January 2024, ready for 80 participants. The primary outcome is objective response rate. Overall survival will not be assessed. More details at ClinicalTrials.gov

“In the absence of a randomized population to compare treatment outcomes, the results of this trial will likely provide limited data upon which to determine the clinical benefits of this novel drug combination strategy,” said Dr. Markman. However, he added, “the results will be helpful in assessing the potential toxicity of this approach.”

Recurrent or metastatic endometrial cancer with proficient mismatch repair. Women with this diagnosis who have progressed after one prior platinum chemotherapy regimen in any setting may wish to consider a randomized, triple-blind, phase 2 trial of pembrolizumab plus favezelimab. Favezelimab, which blocks the lymphocyte activation gene 3 (LAG3), appears to boost the antitumor activity of programmed cell death protein 1 (PD-1) inhibition in other cancers such as classic Hodgkin lymphoma. 

In the trial, participants will be assigned to one of four groups. One group will receive 17 doses of the combination treatment IV every 3 weeks — three doses in the neoadjuvant period and 14 as adjuvant therapy. A second group of individuals will receive IV pembrolizumab monotherapy on the same schedule. A third will be given up to 35 doses of the combo therapy every 3 weeks plus a daily capsule of lenvatinib (Lenvima). The fourth group will receive 35 doses of pembrolizumab plus daily lenvatinib. 

Sites in North Carolina, New Jersey, Pennsylvania, and four countries other than the US started recruiting 60 participants with a solid tumor in September 2023. Pathologic complete response and objective response rate are the primary endpoints. Overall survival over approximately 3.5 years is a secondary endpoint, and QOL will not be measured. More details at ClinicalTrials.gov

Unresectable advanced or metastatic HER2-positive endometrial or ovarian cancer. Adults with one of these diagnoses in whom failed platinum-based therapy has failed may enroll in an open-label, phase 2 study to see whether their disease will respond to the antibody-drug conjugate disitamab vedotin. Everyone in the trial will receive IV disitamab vedotin every 2 weeks for up to approximately 5 years. 

Study sites in California, Connecticut, Michigan, Minnesota, Montana, New York, Ohio, Texas, and Canada began welcoming their 190 participants with one of a range of solid cancers in November 2023. The primary outcome is objective response rate. Overall survival is a secondary measure and QOL will not be tracked. More details at ClinicalTrials.gov

High-risk locally advanced cervical cancer. Girls and women older than 14 years with this cancer that has not progressed after platinum-based chemoradiation are sought for a randomized, quadruple-blind, phase 3 trial to determine whether the investigational immunotherapy volrustomig can slow disease progression. Volrustomig targets PD-1 and cytotoxic T lymphocyte protein 4 (CTLA4) and is being tested in a wide range of solid cancers. 

For approximately 3 years or until disease progression or death, whichever happens first, half of participants will receive IV infusions of volrustomig while the others will receive saline. Asian research sites started seeking the study’s 1000 participants in September 2023, while centers in 12 US states and eight other countries are gearing up for patient enrollment. Progression-free survival in participants with PD-L1 expression is the primary endpoint; overall survival and QOL are secondary endpoints. More details at ClinicalTrials.gov

All trial information is from the National Institutes of Health US National Library of Medicine (online at ClinicalTrials.gov). Dr. Markman declared he is not involved with these trials.

A version of this article appeared on Medscape.com .

This transcript has been edited for clarity.

I want to briefly discuss a critically important topic that cannot be overly emphasized. It is the relevance, the importance, the benefits, and the outcome of HPV vaccination.

The paper I’m referring to was published in Pediatrics in October 2023. It’s titled, “Ten-Year Follow-up of 9-Valent Human Papillomavirus Vaccine: Immunogenicity, Effectiveness, and Safety.”

Let me emphasize that we’re talking about a 10-year follow-up. In this particular paper and analysis, 301 boys — I emphasize boys — were included and 971 girls at 40 different sites in 13 countries, who received the 9-valent vaccine, which includes HPV 16, 18, and seven other types.

These investigators demonstrated that the seropositivity rate 10 years after vaccination remained high for all nine types they looked at. Most importantly, there was not a single case. Not one. Let me repeat this: There was not a single case of high-grade intraepithelial neoplasia, or worse, or condyloma in either males or females. There was not a single case in over 1000 individuals with a follow-up of more than 10 years.

It is difficult to overstate the magnitude of the benefit associated with HPV vaccination for our children and young adults on their risk of developing highly relevant, life-changing, potentially deadly cancers.

For those of you who are interested in this topic — which should include almost all of you, if not all of you — I encourage you to read this very important follow-up paper, again, demonstrating the simple, overwhelming magnitude of the benefit of HPV vaccination. I thank you for your attention.
 

Dr. Markman is a professor in the department of medical oncology and therapeutics research, City of Hope, Duarte, California, and president of medicine and science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline; AstraZeneca.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I want to briefly discuss a critically important topic that cannot be overly emphasized. It is the relevance, the importance, the benefits, and the outcome of HPV vaccination.

The paper I’m referring to was published in Pediatrics in October 2023. It’s titled, “Ten-Year Follow-up of 9-Valent Human Papillomavirus Vaccine: Immunogenicity, Effectiveness, and Safety.”

Let me emphasize that we’re talking about a 10-year follow-up. In this particular paper and analysis, 301 boys — I emphasize boys — were included and 971 girls at 40 different sites in 13 countries, who received the 9-valent vaccine, which includes HPV 16, 18, and seven other types.

These investigators demonstrated that the seropositivity rate 10 years after vaccination remained high for all nine types they looked at. Most importantly, there was not a single case. Not one. Let me repeat this: There was not a single case of high-grade intraepithelial neoplasia, or worse, or condyloma in either males or females. There was not a single case in over 1000 individuals with a follow-up of more than 10 years.

It is difficult to overstate the magnitude of the benefit associated with HPV vaccination for our children and young adults on their risk of developing highly relevant, life-changing, potentially deadly cancers.

For those of you who are interested in this topic — which should include almost all of you, if not all of you — I encourage you to read this very important follow-up paper, again, demonstrating the simple, overwhelming magnitude of the benefit of HPV vaccination. I thank you for your attention.
 

Dr. Markman is a professor in the department of medical oncology and therapeutics research, City of Hope, Duarte, California, and president of medicine and science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline; AstraZeneca.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I want to briefly discuss a critically important topic that cannot be overly emphasized. It is the relevance, the importance, the benefits, and the outcome of HPV vaccination.

The paper I’m referring to was published in Pediatrics in October 2023. It’s titled, “Ten-Year Follow-up of 9-Valent Human Papillomavirus Vaccine: Immunogenicity, Effectiveness, and Safety.”

Let me emphasize that we’re talking about a 10-year follow-up. In this particular paper and analysis, 301 boys — I emphasize boys — were included and 971 girls at 40 different sites in 13 countries, who received the 9-valent vaccine, which includes HPV 16, 18, and seven other types.

These investigators demonstrated that the seropositivity rate 10 years after vaccination remained high for all nine types they looked at. Most importantly, there was not a single case. Not one. Let me repeat this: There was not a single case of high-grade intraepithelial neoplasia, or worse, or condyloma in either males or females. There was not a single case in over 1000 individuals with a follow-up of more than 10 years.

It is difficult to overstate the magnitude of the benefit associated with HPV vaccination for our children and young adults on their risk of developing highly relevant, life-changing, potentially deadly cancers.

For those of you who are interested in this topic — which should include almost all of you, if not all of you — I encourage you to read this very important follow-up paper, again, demonstrating the simple, overwhelming magnitude of the benefit of HPV vaccination. I thank you for your attention.
 

Dr. Markman is a professor in the department of medical oncology and therapeutics research, City of Hope, Duarte, California, and president of medicine and science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline; AstraZeneca.

A version of this article appeared on Medscape.com.