Journal of Clinical Outcomes Management

Patients who mix a diuretic and renin-angiotensin system (RAS) inhibitor with a nonsteroidal anti-inflammatory drug (NSAID) could face a higher risk of developing acute kidney injury (AKI), a new analysis confirms.

The study also looked at risk factors associated with the effect of triple therapy with these agents, which has been called “triple whammy” AKI.

“It’s not that everyone who happens to take this combination of drugs is going to have problems,” Anita Layton, PhD, University of Waterloo, Ontario, said in a statement. “But the research shows it’s enough of a problem that you should exercise caution.”

The study was published online in Mathematical Biosciences.   

In an earlier study, triple therapy with a diuretic, RAS inhibitor, and NSAID was associated with a 31% increased risk for AKI, relative to diuretic and RAS inhibitor therapy only.  

However, the factors that predispose some patients to develop “triple whammy” AKI are unclear.

To better understand the mechanism by which triple therapy increases risk for AKI, Dr. Layton and colleagues used computational models to gauge interactions between concurrent use of a diuretic, a RAS inhibitor, and an NSAID.

They identified dehydration and high sensitivity to drug treatment as key contributing factors to the development of triple whammy AKI.

Their model simulations suggested that low water intake, the myogenic response (that is, the reflex response of arteries and arterioles to changes in blood pressure to maintain consistent blood flow), and drug sensitivity “may predispose patients with hypertension to develop triple whammy-induced AKI,” they wrote.

“We hypothesize that individuals with an impaired myogenic response may be particularly susceptible to triple whammy AKI. Additionally, increased drug sensitivity or low water intake can predispose patients to triple whammy AKI,” they added.

In the absence of additional risk factors, there was no indication of an elevated risk for AKI when an angiotensin-converting enzyme (ACE) inhibitor and NSAID are combined, the study team said. 

In contrast, when an ACE inhibitor, diuretic, and NSAID are combined, critical blood pressure and glomerular filtration rate (GFR) regulatory mechanisms are simultaneously interrupted, they reported.

“Perhaps not unexpectedly, model simulations indicate that triple treatment reduces GFR more than single or double treatments in all individuals. However, under triple treatment, urine volume and GFR have not been predicted to fall sufficiently far to indicate AKI,” they wrote. “This result is consistent with the fact that only a fraction of individuals develop AKI following triple treatment.”

They expect, therefore, that hypertensive patients who are otherwise healthy will be able to withstand triple treatment, in the absence of these aggravating factors, the researchers concluded.

Nonetheless, it’s wise to “always be careful when mixing medications,” Dr. Layton told this news organization.

She noted that “triple whammy AKI is known among kidney researchers and nephrologists. To what extent nonspecialists are aware, it isn’t clear.

“More importantly,” Dr. Layton said, “NSAIDs can be obtained over the counter, and triple whammy AKI isn’t common knowledge outside of the medical community.”

This research was supported by the Canada 150 Research Chair program and by the Natural Sciences and Engineering Research Council of Canada. The authors have declared no conflicts of interest.

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

Patients who mix a diuretic and renin-angiotensin system (RAS) inhibitor with a nonsteroidal anti-inflammatory drug (NSAID) could face a higher risk of developing acute kidney injury (AKI), a new analysis confirms.

The study also looked at risk factors associated with the effect of triple therapy with these agents, which has been called “triple whammy” AKI.

“It’s not that everyone who happens to take this combination of drugs is going to have problems,” Anita Layton, PhD, University of Waterloo, Ontario, said in a statement. “But the research shows it’s enough of a problem that you should exercise caution.”

The study was published online in Mathematical Biosciences.   

In an earlier study, triple therapy with a diuretic, RAS inhibitor, and NSAID was associated with a 31% increased risk for AKI, relative to diuretic and RAS inhibitor therapy only.  

However, the factors that predispose some patients to develop “triple whammy” AKI are unclear.

To better understand the mechanism by which triple therapy increases risk for AKI, Dr. Layton and colleagues used computational models to gauge interactions between concurrent use of a diuretic, a RAS inhibitor, and an NSAID.

They identified dehydration and high sensitivity to drug treatment as key contributing factors to the development of triple whammy AKI.

Their model simulations suggested that low water intake, the myogenic response (that is, the reflex response of arteries and arterioles to changes in blood pressure to maintain consistent blood flow), and drug sensitivity “may predispose patients with hypertension to develop triple whammy-induced AKI,” they wrote.

“We hypothesize that individuals with an impaired myogenic response may be particularly susceptible to triple whammy AKI. Additionally, increased drug sensitivity or low water intake can predispose patients to triple whammy AKI,” they added.

In the absence of additional risk factors, there was no indication of an elevated risk for AKI when an angiotensin-converting enzyme (ACE) inhibitor and NSAID are combined, the study team said. 

In contrast, when an ACE inhibitor, diuretic, and NSAID are combined, critical blood pressure and glomerular filtration rate (GFR) regulatory mechanisms are simultaneously interrupted, they reported.

“Perhaps not unexpectedly, model simulations indicate that triple treatment reduces GFR more than single or double treatments in all individuals. However, under triple treatment, urine volume and GFR have not been predicted to fall sufficiently far to indicate AKI,” they wrote. “This result is consistent with the fact that only a fraction of individuals develop AKI following triple treatment.”

They expect, therefore, that hypertensive patients who are otherwise healthy will be able to withstand triple treatment, in the absence of these aggravating factors, the researchers concluded.

Nonetheless, it’s wise to “always be careful when mixing medications,” Dr. Layton told this news organization.

She noted that “triple whammy AKI is known among kidney researchers and nephrologists. To what extent nonspecialists are aware, it isn’t clear.

“More importantly,” Dr. Layton said, “NSAIDs can be obtained over the counter, and triple whammy AKI isn’t common knowledge outside of the medical community.”

This research was supported by the Canada 150 Research Chair program and by the Natural Sciences and Engineering Research Council of Canada. The authors have declared no conflicts of interest.

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

Patients who mix a diuretic and renin-angiotensin system (RAS) inhibitor with a nonsteroidal anti-inflammatory drug (NSAID) could face a higher risk of developing acute kidney injury (AKI), a new analysis confirms.

The study also looked at risk factors associated with the effect of triple therapy with these agents, which has been called “triple whammy” AKI.

“It’s not that everyone who happens to take this combination of drugs is going to have problems,” Anita Layton, PhD, University of Waterloo, Ontario, said in a statement. “But the research shows it’s enough of a problem that you should exercise caution.”

The study was published online in Mathematical Biosciences.   

In an earlier study, triple therapy with a diuretic, RAS inhibitor, and NSAID was associated with a 31% increased risk for AKI, relative to diuretic and RAS inhibitor therapy only.  

However, the factors that predispose some patients to develop “triple whammy” AKI are unclear.

To better understand the mechanism by which triple therapy increases risk for AKI, Dr. Layton and colleagues used computational models to gauge interactions between concurrent use of a diuretic, a RAS inhibitor, and an NSAID.

They identified dehydration and high sensitivity to drug treatment as key contributing factors to the development of triple whammy AKI.

Their model simulations suggested that low water intake, the myogenic response (that is, the reflex response of arteries and arterioles to changes in blood pressure to maintain consistent blood flow), and drug sensitivity “may predispose patients with hypertension to develop triple whammy-induced AKI,” they wrote.

“We hypothesize that individuals with an impaired myogenic response may be particularly susceptible to triple whammy AKI. Additionally, increased drug sensitivity or low water intake can predispose patients to triple whammy AKI,” they added.

In the absence of additional risk factors, there was no indication of an elevated risk for AKI when an angiotensin-converting enzyme (ACE) inhibitor and NSAID are combined, the study team said. 

In contrast, when an ACE inhibitor, diuretic, and NSAID are combined, critical blood pressure and glomerular filtration rate (GFR) regulatory mechanisms are simultaneously interrupted, they reported.

“Perhaps not unexpectedly, model simulations indicate that triple treatment reduces GFR more than single or double treatments in all individuals. However, under triple treatment, urine volume and GFR have not been predicted to fall sufficiently far to indicate AKI,” they wrote. “This result is consistent with the fact that only a fraction of individuals develop AKI following triple treatment.”

They expect, therefore, that hypertensive patients who are otherwise healthy will be able to withstand triple treatment, in the absence of these aggravating factors, the researchers concluded.

Nonetheless, it’s wise to “always be careful when mixing medications,” Dr. Layton told this news organization.

She noted that “triple whammy AKI is known among kidney researchers and nephrologists. To what extent nonspecialists are aware, it isn’t clear.

“More importantly,” Dr. Layton said, “NSAIDs can be obtained over the counter, and triple whammy AKI isn’t common knowledge outside of the medical community.”

This research was supported by the Canada 150 Research Chair program and by the Natural Sciences and Engineering Research Council of Canada. The authors have declared no conflicts of interest.

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

After hospitalization, COVID-19 patients 9 hours per day of sedentary time at 3-6 months after discharge, according to data from 37 individuals.

COVID-19 patients experience a wide range of clinical manifestations, and roughly half of those who were hospitalized for COVID-19 report persisting symptoms both physical and mental up to a year after discharge, Bram van Bakel, MD, of Radboud University Medical Center, Nijmegen, the Netherlands, said in a presentation at the presentation at the annual congress of the European Association of Preventive Cardiology.

However, data on physical activity patterns and the impact on recovery after postinfection hospital discharge are limited, he said. Dr. van Bakel and colleagues aimed to assess physical activity, sedentary behavior, and sleep duration in COVID-19 patients at 3-6 months after hospital discharge to explore the association with patient characteristics, disease severity and cardiac dysfunction.

“We hypothesized that COVID-19 survivors will demonstrate low volumes of physical activity and a high sedentary time, especially those with a more severe disease course,” such as longer hospital duration and admission to intensive care, cardiac dysfunction, and persistent symptoms at 3-6 months post discharge, he said.

Dr. van Bakel and colleagues enrolled 37 adult patients in a cross-sectional cohort study. They objectively assessed physical activity, sedentary behavior, and sleep duration for 24 hrs/day during 8 subsequent days in COVID-19 survivors at 3-6 months post hospitalization. The average age of the patients was 60 years, 78% were male, and the average assessment time was 125 days after hospital discharge.

The researchers compared activity patterns based on patient and disease characteristics, cardiac biomarker release during hospitalization, abnormal transthoracic echocardiogram regarding left and right ventricular function and volumes at 3-6 months of follow-up, and the persistence of symptoms after discharge.

Overall, patients spent a median of 4.2 hours per day in light-intensity physical activity, and 1 hour per day in moderate to vigorous physical activity. The overall median time spent sitting was 9.8 hours per day; this was accumulated in approximately 6 prolonged sitting periods of 30 minutes or more and 41.1 short sitting periods of less than 30 minutes.

The median sleep duration was 9.8 hours per day; sleep duration was significantly higher in women, compared with men (9.2 vs. 8.5 hours/day; P = .03), and in patients with persistent symptoms, compared with those without persistent symptoms (9.1 hrs/day vs. 8.3 hrs/day; P = .02). No other differences in activity or sitting patterns appeared among subgroups. Sedentary time of 10 hours or more per day overall puts individuals at increased risk for detrimental health effects, Dr. van Bakel said.

The study findings were limited by the small sample and cross-sectional design, he noted.

However, the results suggest that COVID-19 patients spent most of their time sedentary within the first 3-6 months after hospital discharge. The similar activity patterns across subgroups support a uniform approach to rehabilitation for these patients to target persisting symptoms and prevent long-term health consequences, said Dr. van Bakel. Further studies are warranted in a larger cohort with a prospective design and longitudinal follow-up.

The current study “highlights the need for ongoing rehabilitation in severe COVID-19 survivors after hospitalization to restore premorbid function and endurance,” Alba Miranda Azola, MD, of Johns Hopkins University, Baltimore, said in an interview.

“The findings regarding inactivity are not surprising,” said Dr. Azola. “Immobility during hospitalization results in muscle atrophy and marked decreased endurance. The need for prolonged use of sedation and paralytics during intensive care stays of severe COVID-19 patients is associated with critical illness myopathy. Also, many patients continue to experience hypoxia and dyspnea on exertion for several months after leaving the hospital. The functional impairments and limited activity tolerance often preclude patients from engaging on outpatient rehabilitation programs.

“I do think it surprising that the level of inactivity observed was independent of disease severity and patient factors, but it definitely speaks to the importance of establishing post hospitalization follow-up care that focuses on restoring function and mobility,” Dr. Azola noted.

The study findings may have long-term clinical implications, as COVID-19 survivors who experience functional decline that limits activity and who continue to lead a sedentary lifestyle may be at increased risk for health issues such as heart disease and type 2 diabetes, Dr. Azola said. 

Rigorous research is needed to study the functional and health impact of rehabilitation interventions during and after hospitalization, she emphasized. “Additionally, studies are needed on innovative rehabilitation interventions that improve accessibility to services to patients.”

The study received no outside funding. The researchers and Dr. Azola had no financial conflicts to disclose. Dr. Azola had no financial conflicts to disclose.

After hospitalization, COVID-19 patients 9 hours per day of sedentary time at 3-6 months after discharge, according to data from 37 individuals.

COVID-19 patients experience a wide range of clinical manifestations, and roughly half of those who were hospitalized for COVID-19 report persisting symptoms both physical and mental up to a year after discharge, Bram van Bakel, MD, of Radboud University Medical Center, Nijmegen, the Netherlands, said in a presentation at the presentation at the annual congress of the European Association of Preventive Cardiology.

However, data on physical activity patterns and the impact on recovery after postinfection hospital discharge are limited, he said. Dr. van Bakel and colleagues aimed to assess physical activity, sedentary behavior, and sleep duration in COVID-19 patients at 3-6 months after hospital discharge to explore the association with patient characteristics, disease severity and cardiac dysfunction.

“We hypothesized that COVID-19 survivors will demonstrate low volumes of physical activity and a high sedentary time, especially those with a more severe disease course,” such as longer hospital duration and admission to intensive care, cardiac dysfunction, and persistent symptoms at 3-6 months post discharge, he said.

Dr. van Bakel and colleagues enrolled 37 adult patients in a cross-sectional cohort study. They objectively assessed physical activity, sedentary behavior, and sleep duration for 24 hrs/day during 8 subsequent days in COVID-19 survivors at 3-6 months post hospitalization. The average age of the patients was 60 years, 78% were male, and the average assessment time was 125 days after hospital discharge.

The researchers compared activity patterns based on patient and disease characteristics, cardiac biomarker release during hospitalization, abnormal transthoracic echocardiogram regarding left and right ventricular function and volumes at 3-6 months of follow-up, and the persistence of symptoms after discharge.

Overall, patients spent a median of 4.2 hours per day in light-intensity physical activity, and 1 hour per day in moderate to vigorous physical activity. The overall median time spent sitting was 9.8 hours per day; this was accumulated in approximately 6 prolonged sitting periods of 30 minutes or more and 41.1 short sitting periods of less than 30 minutes.

The median sleep duration was 9.8 hours per day; sleep duration was significantly higher in women, compared with men (9.2 vs. 8.5 hours/day; P = .03), and in patients with persistent symptoms, compared with those without persistent symptoms (9.1 hrs/day vs. 8.3 hrs/day; P = .02). No other differences in activity or sitting patterns appeared among subgroups. Sedentary time of 10 hours or more per day overall puts individuals at increased risk for detrimental health effects, Dr. van Bakel said.

The study findings were limited by the small sample and cross-sectional design, he noted.

However, the results suggest that COVID-19 patients spent most of their time sedentary within the first 3-6 months after hospital discharge. The similar activity patterns across subgroups support a uniform approach to rehabilitation for these patients to target persisting symptoms and prevent long-term health consequences, said Dr. van Bakel. Further studies are warranted in a larger cohort with a prospective design and longitudinal follow-up.

The current study “highlights the need for ongoing rehabilitation in severe COVID-19 survivors after hospitalization to restore premorbid function and endurance,” Alba Miranda Azola, MD, of Johns Hopkins University, Baltimore, said in an interview.

“The findings regarding inactivity are not surprising,” said Dr. Azola. “Immobility during hospitalization results in muscle atrophy and marked decreased endurance. The need for prolonged use of sedation and paralytics during intensive care stays of severe COVID-19 patients is associated with critical illness myopathy. Also, many patients continue to experience hypoxia and dyspnea on exertion for several months after leaving the hospital. The functional impairments and limited activity tolerance often preclude patients from engaging on outpatient rehabilitation programs.

“I do think it surprising that the level of inactivity observed was independent of disease severity and patient factors, but it definitely speaks to the importance of establishing post hospitalization follow-up care that focuses on restoring function and mobility,” Dr. Azola noted.

The study findings may have long-term clinical implications, as COVID-19 survivors who experience functional decline that limits activity and who continue to lead a sedentary lifestyle may be at increased risk for health issues such as heart disease and type 2 diabetes, Dr. Azola said. 

Rigorous research is needed to study the functional and health impact of rehabilitation interventions during and after hospitalization, she emphasized. “Additionally, studies are needed on innovative rehabilitation interventions that improve accessibility to services to patients.”

The study received no outside funding. The researchers and Dr. Azola had no financial conflicts to disclose. Dr. Azola had no financial conflicts to disclose.

After hospitalization, COVID-19 patients 9 hours per day of sedentary time at 3-6 months after discharge, according to data from 37 individuals.

COVID-19 patients experience a wide range of clinical manifestations, and roughly half of those who were hospitalized for COVID-19 report persisting symptoms both physical and mental up to a year after discharge, Bram van Bakel, MD, of Radboud University Medical Center, Nijmegen, the Netherlands, said in a presentation at the presentation at the annual congress of the European Association of Preventive Cardiology.

However, data on physical activity patterns and the impact on recovery after postinfection hospital discharge are limited, he said. Dr. van Bakel and colleagues aimed to assess physical activity, sedentary behavior, and sleep duration in COVID-19 patients at 3-6 months after hospital discharge to explore the association with patient characteristics, disease severity and cardiac dysfunction.

“We hypothesized that COVID-19 survivors will demonstrate low volumes of physical activity and a high sedentary time, especially those with a more severe disease course,” such as longer hospital duration and admission to intensive care, cardiac dysfunction, and persistent symptoms at 3-6 months post discharge, he said.

Dr. van Bakel and colleagues enrolled 37 adult patients in a cross-sectional cohort study. They objectively assessed physical activity, sedentary behavior, and sleep duration for 24 hrs/day during 8 subsequent days in COVID-19 survivors at 3-6 months post hospitalization. The average age of the patients was 60 years, 78% were male, and the average assessment time was 125 days after hospital discharge.

The researchers compared activity patterns based on patient and disease characteristics, cardiac biomarker release during hospitalization, abnormal transthoracic echocardiogram regarding left and right ventricular function and volumes at 3-6 months of follow-up, and the persistence of symptoms after discharge.

Overall, patients spent a median of 4.2 hours per day in light-intensity physical activity, and 1 hour per day in moderate to vigorous physical activity. The overall median time spent sitting was 9.8 hours per day; this was accumulated in approximately 6 prolonged sitting periods of 30 minutes or more and 41.1 short sitting periods of less than 30 minutes.

The median sleep duration was 9.8 hours per day; sleep duration was significantly higher in women, compared with men (9.2 vs. 8.5 hours/day; P = .03), and in patients with persistent symptoms, compared with those without persistent symptoms (9.1 hrs/day vs. 8.3 hrs/day; P = .02). No other differences in activity or sitting patterns appeared among subgroups. Sedentary time of 10 hours or more per day overall puts individuals at increased risk for detrimental health effects, Dr. van Bakel said.

The study findings were limited by the small sample and cross-sectional design, he noted.

However, the results suggest that COVID-19 patients spent most of their time sedentary within the first 3-6 months after hospital discharge. The similar activity patterns across subgroups support a uniform approach to rehabilitation for these patients to target persisting symptoms and prevent long-term health consequences, said Dr. van Bakel. Further studies are warranted in a larger cohort with a prospective design and longitudinal follow-up.

The current study “highlights the need for ongoing rehabilitation in severe COVID-19 survivors after hospitalization to restore premorbid function and endurance,” Alba Miranda Azola, MD, of Johns Hopkins University, Baltimore, said in an interview.

“The findings regarding inactivity are not surprising,” said Dr. Azola. “Immobility during hospitalization results in muscle atrophy and marked decreased endurance. The need for prolonged use of sedation and paralytics during intensive care stays of severe COVID-19 patients is associated with critical illness myopathy. Also, many patients continue to experience hypoxia and dyspnea on exertion for several months after leaving the hospital. The functional impairments and limited activity tolerance often preclude patients from engaging on outpatient rehabilitation programs.

“I do think it surprising that the level of inactivity observed was independent of disease severity and patient factors, but it definitely speaks to the importance of establishing post hospitalization follow-up care that focuses on restoring function and mobility,” Dr. Azola noted.

The study findings may have long-term clinical implications, as COVID-19 survivors who experience functional decline that limits activity and who continue to lead a sedentary lifestyle may be at increased risk for health issues such as heart disease and type 2 diabetes, Dr. Azola said. 

Rigorous research is needed to study the functional and health impact of rehabilitation interventions during and after hospitalization, she emphasized. “Additionally, studies are needed on innovative rehabilitation interventions that improve accessibility to services to patients.”

The study received no outside funding. The researchers and Dr. Azola had no financial conflicts to disclose. Dr. Azola had no financial conflicts to disclose.

The Food and Drug Administration announced on May 10 that it is taking several steps to improve the supply of baby formula in the United States.

The nationwide formula shortage has grown worse in recent weeks due to supply chain issues and a recall of certain Abbott Nutrition products, including major labels such as Similac, Alimentum, and EleCare.

“We recognize that many consumers have been unable to access infant formula and critical medical foods they are accustomed to using and are frustrated by their inability to do so,” FDA Commissioner Robert Califf, MD, said in a statement.

“We are doing everything in our power to ensure there is adequate product available where and when they need it,” he said.

About three-quarters of babies are fed formula for the first 6 months of their lives as a substitute for human milk, Axios reported.

In mid-February, the FDA warned consumers not to use certain powdered infant formula products from Abbott’s facility in Sturgis, Mich. Since then, the FDA has been working with Abbott and other manufacturers to increase the supply in the U.S. market.

“In fact, other infant formula manufacturers are meeting or exceeding capacity levels to meet current demand,” the FDA said in the statement. “Notably, more infant formula was purchased in the month of April than in the month prior to the recall.”

The FDA released a list of steps the agency is taking to increase supply, such as meeting with major infant formula makers to increase output and prioritize product lines in high demand, particularly specialty formulas for infants with allergies or specific diet needs.

But other manufacturers have struggled to quickly increase production because their operations tend to focus on a steady level of supply, according to The New York Times.

“Some industries are very good at ramping up and ramping down,” Rudi Leuschner, PhD, an associate professor of supply chain management at Rutgers Business School, Newark, N.J., told the newspaper.

“You flip a switch and they can produce 10 times as much,” he said. “Baby formula is not that type of a product.”

The FDA is also keeping an eye on the infant formula shortage by using the agency’s 21 Forward food supply chain continuity system. The system was developed during the pandemic to provide a full understanding of how COVID-19 is impacting food supply chains, the FDA said.

The FDA is compiling data on trends for in-stock rates at national and regional levels to understand where infant formula is available and where it should go.

Products are also being brought in from other countries, the FDA said. The agency is trying to speed up the process to get more formula into the U.S. and move it more quickly around the country.

For babies on a special diet, the FDA has decided to release some Abbott products that have been on hold at the Sturgis facility to those who need an urgent supply of metabolic formulas, on a case-by-case basis.

“In these circumstances, the benefit of allowing caregivers, in consultation with their health care providers, to access these products may outweigh the potential risk of bacterial infection,” the FDA said in the statement.

The FDA continues to advise against making homemade infant formulas and recommends talking to the child’s health care provider for recommendations on changing feeding practices or switching to other formulas, if necessary.

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

The Food and Drug Administration announced on May 10 that it is taking several steps to improve the supply of baby formula in the United States.

The nationwide formula shortage has grown worse in recent weeks due to supply chain issues and a recall of certain Abbott Nutrition products, including major labels such as Similac, Alimentum, and EleCare.

“We recognize that many consumers have been unable to access infant formula and critical medical foods they are accustomed to using and are frustrated by their inability to do so,” FDA Commissioner Robert Califf, MD, said in a statement.

“We are doing everything in our power to ensure there is adequate product available where and when they need it,” he said.

About three-quarters of babies are fed formula for the first 6 months of their lives as a substitute for human milk, Axios reported.

In mid-February, the FDA warned consumers not to use certain powdered infant formula products from Abbott’s facility in Sturgis, Mich. Since then, the FDA has been working with Abbott and other manufacturers to increase the supply in the U.S. market.

“In fact, other infant formula manufacturers are meeting or exceeding capacity levels to meet current demand,” the FDA said in the statement. “Notably, more infant formula was purchased in the month of April than in the month prior to the recall.”

The FDA released a list of steps the agency is taking to increase supply, such as meeting with major infant formula makers to increase output and prioritize product lines in high demand, particularly specialty formulas for infants with allergies or specific diet needs.

But other manufacturers have struggled to quickly increase production because their operations tend to focus on a steady level of supply, according to The New York Times.

“Some industries are very good at ramping up and ramping down,” Rudi Leuschner, PhD, an associate professor of supply chain management at Rutgers Business School, Newark, N.J., told the newspaper.

“You flip a switch and they can produce 10 times as much,” he said. “Baby formula is not that type of a product.”

The FDA is also keeping an eye on the infant formula shortage by using the agency’s 21 Forward food supply chain continuity system. The system was developed during the pandemic to provide a full understanding of how COVID-19 is impacting food supply chains, the FDA said.

The FDA is compiling data on trends for in-stock rates at national and regional levels to understand where infant formula is available and where it should go.

Products are also being brought in from other countries, the FDA said. The agency is trying to speed up the process to get more formula into the U.S. and move it more quickly around the country.

For babies on a special diet, the FDA has decided to release some Abbott products that have been on hold at the Sturgis facility to those who need an urgent supply of metabolic formulas, on a case-by-case basis.

“In these circumstances, the benefit of allowing caregivers, in consultation with their health care providers, to access these products may outweigh the potential risk of bacterial infection,” the FDA said in the statement.

The FDA continues to advise against making homemade infant formulas and recommends talking to the child’s health care provider for recommendations on changing feeding practices or switching to other formulas, if necessary.

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

The Food and Drug Administration announced on May 10 that it is taking several steps to improve the supply of baby formula in the United States.

The nationwide formula shortage has grown worse in recent weeks due to supply chain issues and a recall of certain Abbott Nutrition products, including major labels such as Similac, Alimentum, and EleCare.

“We recognize that many consumers have been unable to access infant formula and critical medical foods they are accustomed to using and are frustrated by their inability to do so,” FDA Commissioner Robert Califf, MD, said in a statement.

“We are doing everything in our power to ensure there is adequate product available where and when they need it,” he said.

About three-quarters of babies are fed formula for the first 6 months of their lives as a substitute for human milk, Axios reported.

In mid-February, the FDA warned consumers not to use certain powdered infant formula products from Abbott’s facility in Sturgis, Mich. Since then, the FDA has been working with Abbott and other manufacturers to increase the supply in the U.S. market.

“In fact, other infant formula manufacturers are meeting or exceeding capacity levels to meet current demand,” the FDA said in the statement. “Notably, more infant formula was purchased in the month of April than in the month prior to the recall.”

The FDA released a list of steps the agency is taking to increase supply, such as meeting with major infant formula makers to increase output and prioritize product lines in high demand, particularly specialty formulas for infants with allergies or specific diet needs.

But other manufacturers have struggled to quickly increase production because their operations tend to focus on a steady level of supply, according to The New York Times.

“Some industries are very good at ramping up and ramping down,” Rudi Leuschner, PhD, an associate professor of supply chain management at Rutgers Business School, Newark, N.J., told the newspaper.

“You flip a switch and they can produce 10 times as much,” he said. “Baby formula is not that type of a product.”

The FDA is also keeping an eye on the infant formula shortage by using the agency’s 21 Forward food supply chain continuity system. The system was developed during the pandemic to provide a full understanding of how COVID-19 is impacting food supply chains, the FDA said.

The FDA is compiling data on trends for in-stock rates at national and regional levels to understand where infant formula is available and where it should go.

Products are also being brought in from other countries, the FDA said. The agency is trying to speed up the process to get more formula into the U.S. and move it more quickly around the country.

For babies on a special diet, the FDA has decided to release some Abbott products that have been on hold at the Sturgis facility to those who need an urgent supply of metabolic formulas, on a case-by-case basis.

“In these circumstances, the benefit of allowing caregivers, in consultation with their health care providers, to access these products may outweigh the potential risk of bacterial infection,” the FDA said in the statement.

The FDA continues to advise against making homemade infant formulas and recommends talking to the child’s health care provider for recommendations on changing feeding practices or switching to other formulas, if necessary.

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

Reduced exercise capacity and peak ventilation were significant predictors of early mortality in adults with chronic obstructive pulmonary disease, based on data from 126 individuals.

Cardiopulmonary exercise testing (CPET) is a common assessment for cardiorespiratory disease patients, but its role as a predictor of clinically relevant outcomes in chronic obstructive pulmonary disease (COPD) has not been investigated, and data on changes in exercise capacity over time in COPD patients are limited, wrote Cassia da Luz Goulart, MD, of the Federal University of São Carlos, Brazil, and colleagues.

The researchers hypothesized that CPET threshold values could be used as predictors of mortality in COPD.

In a prospective study published in Respiratory Medicine, the researchers identified 126 adults with COPD who were followed for 42 months. At study entry, each patient completed a clinical evaluation, followed by a pulmonary function test and CPET. The average age of the patients was 65 years, and 73% were men. All patients were on optimal medical management for COPD.

The researchers recorded data on peak oxygen consumption (VO₂, mL/min), VCO₂ (mL/min), minute ventilation (VE, L/min), the oxygen uptake efficiency slope (OUES), and ventilatory efficiency (the VE/VCO₂ slope).

The participants performed CPET on a cycle ergometer, with breath-by-breath analysis measured throughout the test using a computer-based system.

A total of 48 patients (38%) died during the 42-month follow-up period. Overall, the significant predictors of mortality were VE/VCO₂ slope of 30 or higher, peak VE of 25.7 L/min, and peak VO₂ ≤ 13.8 mLO₂ kg^–1 min^–1 were strong predictors of mortality in COPD patients in a Cox regression analysis.

When comparing the 78 survivors to the 48 nonsurvivors, the researchers found that the nonsurvivors were significantly more likely to be women, with worse lung function, inspiratory muscle weakness, and poorer CPET responses (P < .050 for all).

“The VE peak response is directly related to the FEV₁ in COPD patients, factors such as dyspnea and increased leg discomfort negatively impact the VE response during exercise,” the researchers wrote in their discussion of the findings. In this context, our results may hold clinical utility in refining the prognostic accuracy when a patient with COPD has a VE peak ≤ 25.7 L/min,” they explained.

The study findings were limited by the inability to assess complete pulmonary function in the COPD patients, and the assessment only of three CPET measures, the researchers noted.

However, the results support the use of CPET as a clinical assessment tool for COPD patients, they said. “Moreover, therapeutic approaches, such as cardiopulmonary rehabilitation, may consider focusing on improving these metabolic and ventilatory markers as an indicator of clinical improvement and prognosis in patients with COPD,” they added.

The study was supported by the Fundação de Amparo a Pesquisa do Estado de São Paulo, Brazil, and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil. The researchers had no financial conflicts to disclose.

Reduced exercise capacity and peak ventilation were significant predictors of early mortality in adults with chronic obstructive pulmonary disease, based on data from 126 individuals.

Cardiopulmonary exercise testing (CPET) is a common assessment for cardiorespiratory disease patients, but its role as a predictor of clinically relevant outcomes in chronic obstructive pulmonary disease (COPD) has not been investigated, and data on changes in exercise capacity over time in COPD patients are limited, wrote Cassia da Luz Goulart, MD, of the Federal University of São Carlos, Brazil, and colleagues.

The researchers hypothesized that CPET threshold values could be used as predictors of mortality in COPD.

In a prospective study published in Respiratory Medicine, the researchers identified 126 adults with COPD who were followed for 42 months. At study entry, each patient completed a clinical evaluation, followed by a pulmonary function test and CPET. The average age of the patients was 65 years, and 73% were men. All patients were on optimal medical management for COPD.

The researchers recorded data on peak oxygen consumption (VO₂, mL/min), VCO₂ (mL/min), minute ventilation (VE, L/min), the oxygen uptake efficiency slope (OUES), and ventilatory efficiency (the VE/VCO₂ slope).

The participants performed CPET on a cycle ergometer, with breath-by-breath analysis measured throughout the test using a computer-based system.

A total of 48 patients (38%) died during the 42-month follow-up period. Overall, the significant predictors of mortality were VE/VCO₂ slope of 30 or higher, peak VE of 25.7 L/min, and peak VO₂ ≤ 13.8 mLO₂ kg^–1 min^–1 were strong predictors of mortality in COPD patients in a Cox regression analysis.

When comparing the 78 survivors to the 48 nonsurvivors, the researchers found that the nonsurvivors were significantly more likely to be women, with worse lung function, inspiratory muscle weakness, and poorer CPET responses (P < .050 for all).

“The VE peak response is directly related to the FEV₁ in COPD patients, factors such as dyspnea and increased leg discomfort negatively impact the VE response during exercise,” the researchers wrote in their discussion of the findings. In this context, our results may hold clinical utility in refining the prognostic accuracy when a patient with COPD has a VE peak ≤ 25.7 L/min,” they explained.

The study findings were limited by the inability to assess complete pulmonary function in the COPD patients, and the assessment only of three CPET measures, the researchers noted.

However, the results support the use of CPET as a clinical assessment tool for COPD patients, they said. “Moreover, therapeutic approaches, such as cardiopulmonary rehabilitation, may consider focusing on improving these metabolic and ventilatory markers as an indicator of clinical improvement and prognosis in patients with COPD,” they added.

The study was supported by the Fundação de Amparo a Pesquisa do Estado de São Paulo, Brazil, and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil. The researchers had no financial conflicts to disclose.

Reduced exercise capacity and peak ventilation were significant predictors of early mortality in adults with chronic obstructive pulmonary disease, based on data from 126 individuals.

Cardiopulmonary exercise testing (CPET) is a common assessment for cardiorespiratory disease patients, but its role as a predictor of clinically relevant outcomes in chronic obstructive pulmonary disease (COPD) has not been investigated, and data on changes in exercise capacity over time in COPD patients are limited, wrote Cassia da Luz Goulart, MD, of the Federal University of São Carlos, Brazil, and colleagues.

The researchers hypothesized that CPET threshold values could be used as predictors of mortality in COPD.

In a prospective study published in Respiratory Medicine, the researchers identified 126 adults with COPD who were followed for 42 months. At study entry, each patient completed a clinical evaluation, followed by a pulmonary function test and CPET. The average age of the patients was 65 years, and 73% were men. All patients were on optimal medical management for COPD.

The researchers recorded data on peak oxygen consumption (VO₂, mL/min), VCO₂ (mL/min), minute ventilation (VE, L/min), the oxygen uptake efficiency slope (OUES), and ventilatory efficiency (the VE/VCO₂ slope).

The participants performed CPET on a cycle ergometer, with breath-by-breath analysis measured throughout the test using a computer-based system.

A total of 48 patients (38%) died during the 42-month follow-up period. Overall, the significant predictors of mortality were VE/VCO₂ slope of 30 or higher, peak VE of 25.7 L/min, and peak VO₂ ≤ 13.8 mLO₂ kg^–1 min^–1 were strong predictors of mortality in COPD patients in a Cox regression analysis.

When comparing the 78 survivors to the 48 nonsurvivors, the researchers found that the nonsurvivors were significantly more likely to be women, with worse lung function, inspiratory muscle weakness, and poorer CPET responses (P < .050 for all).

“The VE peak response is directly related to the FEV₁ in COPD patients, factors such as dyspnea and increased leg discomfort negatively impact the VE response during exercise,” the researchers wrote in their discussion of the findings. In this context, our results may hold clinical utility in refining the prognostic accuracy when a patient with COPD has a VE peak ≤ 25.7 L/min,” they explained.

The study findings were limited by the inability to assess complete pulmonary function in the COPD patients, and the assessment only of three CPET measures, the researchers noted.

However, the results support the use of CPET as a clinical assessment tool for COPD patients, they said. “Moreover, therapeutic approaches, such as cardiopulmonary rehabilitation, may consider focusing on improving these metabolic and ventilatory markers as an indicator of clinical improvement and prognosis in patients with COPD,” they added.

The study was supported by the Fundação de Amparo a Pesquisa do Estado de São Paulo, Brazil, and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil. The researchers had no financial conflicts to disclose.

While previous research suggests that dietary supplementation with L-serine may be beneficial for patients with Alzheimer’s disease (AD), a new study cast doubt on the potential efficacy, and even the safety, of this treatment.

When given to patients with AD, L-serine supplements could be driving abnormally increased serine levels in the brain even higher, potentially accelerating neuronal death, according to study author Xu Chen, PhD, of the University of California, San Diego, and colleagues.

This conclusion conflicts with a 2020 study by Juliette Le Douce, PhD, and colleagues, who reported that oral L-serine supplementation may act as a “ready-to-use therapy” for AD, based on their findings that patients with AD had low levels of PHGDH, an enzyme necessary for synthesizing serine, and AD-like mice had low levels of serine.

Writing in Cell Metabolism, Dr. Chen and colleagues framed the present study, and their findings, in this context.

“In contrast to the work of Le Douce et al., here we report that PHGDH mRNA and protein levels are increased in the brains of two mouse models of AD and/or tauopathy, and are also progressively increased in human brains with no, early, and late AD pathology, as well as in people with no, asymptomatic, and symptomatic AD,” they wrote.

They suggested adjusting clinical recommendations for L-serine, the form of the amino acid commonly found in supplements. In the body, L-serine is converted to D-serine, which acts on the NMDA receptor (NMDAR).

‘Long-term use of D-serine contributes to neuronal death’ suggests research

“We feel oral L-serine as a ready-to-use therapy to AD warrants precaution,” Dr. Chen and colleagues wrote. “This is because despite being a cognitive enhancer, some [research] suggests that long-term use of D-serine contributes to neuronal death in AD through excitotoxicity. Furthermore, D-serine, as a co-agonist of NMDAR, would be expected to oppose NMDAR antagonists, which have proven clinical benefits in treating AD.”

According to principal author Sheng Zhong, PhD, of the University of California, San Diego, “Research is needed to test if targeting PHGDH can ameliorate cognitive decline in AD.”

Dr. Zhong also noted that the present findings support the “promise of using a specific RNA in blood as a biomarker for early detection of Alzheimer’s disease.” This approach is currently being validated at UCSD Shiley-Marcos Alzheimer’s Disease Research Center, he added.

Roles of PHGDH and serine in Alzheimer’s disease require further study

Commenting on both studies, Steve W. Barger, PhD, of the University of Arkansas for Medical Sciences, Little Rock, suggested that more work is needed to better understand the roles of PHGDH and serine in AD before clinical applications can be considered.

“In the end, these two studies fail to provide the clarity we need in designing evidence-based therapeutic hypotheses,” Dr. Barger said in an interview. “We still do not have a firm grasp on the role that D-serine plays in AD. Indeed, the evidence regarding even a single enzyme contributing to its levels is ambiguous.”

Dr. Barger, who has published extensively on the topic of neuronal death, with a particular focus on Alzheimer’s disease, noted that “determination of what happens to D-serine levels in AD has been of interest for decades,” but levels of the amino acid have been notoriously challenging to measure because “D-serine can disappear rapidly from the brain and its fluids after death.”

While Dr. Le Douce and colleagues did measure levels of serine in mice, Dr. Barger noted that the study by Dr. Chen and colleagues was conducted with more “quantitatively rigorous methods.” Even though Dr. Chen and colleagues “did not assay the levels of D-serine itself ... the implication of their findings is that PHGDH is poised to elevate this critical neurotransmitter,” leading to their conclusion that serine supplementation is “potentially dangerous.”

At this point, it may be too early to tell, according to Dr. Barger.

He suggested that conclusions drawn from PHGDH levels alone are “always limited,” and conclusions based on serine levels may be equally dubious, considering that the activities and effects of serine “are quite complex,” and may be influenced by other physiologic processes, including the effects of gut bacteria.

Instead, Dr. Barger suggested that changes in PHGDH and serine may be interpreted as signals coming from a more relevant process upstream: glucose metabolism.

“What we can say confidently is that the glucose metabolism that PHGDH connects to D-serine is most definitely a factor in AD,” he said. “Countless studies have documented what now appears to be a universal decline in glucose delivery to the cerebral cortex, even before frank dementia sets in.”

Dr. Barger noted that declining glucose delivery coincides with some of the earliest events in the development of AD, perhaps “linking accumulation of amyloid β-peptide to subsequent neurofibrillary tangles and tissue atrophy.”

Dr. Barger’s own work recently demonstrated that AD is associated with “an irregularity in the insertion of a specific glucose transporter (GLUT1) into the cell surface” of astrocytes.

“It could be more effective to direct therapeutic interventions at these events lying upstream of PHGDH or serine,” he concluded.

The study was partly supported by a Kreuger v. Wyeth research award. The investigators and Dr. Barger reported no conflicts of interest.

While previous research suggests that dietary supplementation with L-serine may be beneficial for patients with Alzheimer’s disease (AD), a new study cast doubt on the potential efficacy, and even the safety, of this treatment.

When given to patients with AD, L-serine supplements could be driving abnormally increased serine levels in the brain even higher, potentially accelerating neuronal death, according to study author Xu Chen, PhD, of the University of California, San Diego, and colleagues.

This conclusion conflicts with a 2020 study by Juliette Le Douce, PhD, and colleagues, who reported that oral L-serine supplementation may act as a “ready-to-use therapy” for AD, based on their findings that patients with AD had low levels of PHGDH, an enzyme necessary for synthesizing serine, and AD-like mice had low levels of serine.

Writing in Cell Metabolism, Dr. Chen and colleagues framed the present study, and their findings, in this context.

“In contrast to the work of Le Douce et al., here we report that PHGDH mRNA and protein levels are increased in the brains of two mouse models of AD and/or tauopathy, and are also progressively increased in human brains with no, early, and late AD pathology, as well as in people with no, asymptomatic, and symptomatic AD,” they wrote.

They suggested adjusting clinical recommendations for L-serine, the form of the amino acid commonly found in supplements. In the body, L-serine is converted to D-serine, which acts on the NMDA receptor (NMDAR).

‘Long-term use of D-serine contributes to neuronal death’ suggests research

“We feel oral L-serine as a ready-to-use therapy to AD warrants precaution,” Dr. Chen and colleagues wrote. “This is because despite being a cognitive enhancer, some [research] suggests that long-term use of D-serine contributes to neuronal death in AD through excitotoxicity. Furthermore, D-serine, as a co-agonist of NMDAR, would be expected to oppose NMDAR antagonists, which have proven clinical benefits in treating AD.”

According to principal author Sheng Zhong, PhD, of the University of California, San Diego, “Research is needed to test if targeting PHGDH can ameliorate cognitive decline in AD.”

Dr. Zhong also noted that the present findings support the “promise of using a specific RNA in blood as a biomarker for early detection of Alzheimer’s disease.” This approach is currently being validated at UCSD Shiley-Marcos Alzheimer’s Disease Research Center, he added.

Roles of PHGDH and serine in Alzheimer’s disease require further study

Commenting on both studies, Steve W. Barger, PhD, of the University of Arkansas for Medical Sciences, Little Rock, suggested that more work is needed to better understand the roles of PHGDH and serine in AD before clinical applications can be considered.

“In the end, these two studies fail to provide the clarity we need in designing evidence-based therapeutic hypotheses,” Dr. Barger said in an interview. “We still do not have a firm grasp on the role that D-serine plays in AD. Indeed, the evidence regarding even a single enzyme contributing to its levels is ambiguous.”

Dr. Barger, who has published extensively on the topic of neuronal death, with a particular focus on Alzheimer’s disease, noted that “determination of what happens to D-serine levels in AD has been of interest for decades,” but levels of the amino acid have been notoriously challenging to measure because “D-serine can disappear rapidly from the brain and its fluids after death.”

While Dr. Le Douce and colleagues did measure levels of serine in mice, Dr. Barger noted that the study by Dr. Chen and colleagues was conducted with more “quantitatively rigorous methods.” Even though Dr. Chen and colleagues “did not assay the levels of D-serine itself ... the implication of their findings is that PHGDH is poised to elevate this critical neurotransmitter,” leading to their conclusion that serine supplementation is “potentially dangerous.”

At this point, it may be too early to tell, according to Dr. Barger.

He suggested that conclusions drawn from PHGDH levels alone are “always limited,” and conclusions based on serine levels may be equally dubious, considering that the activities and effects of serine “are quite complex,” and may be influenced by other physiologic processes, including the effects of gut bacteria.

Instead, Dr. Barger suggested that changes in PHGDH and serine may be interpreted as signals coming from a more relevant process upstream: glucose metabolism.

“What we can say confidently is that the glucose metabolism that PHGDH connects to D-serine is most definitely a factor in AD,” he said. “Countless studies have documented what now appears to be a universal decline in glucose delivery to the cerebral cortex, even before frank dementia sets in.”

Dr. Barger noted that declining glucose delivery coincides with some of the earliest events in the development of AD, perhaps “linking accumulation of amyloid β-peptide to subsequent neurofibrillary tangles and tissue atrophy.”

Dr. Barger’s own work recently demonstrated that AD is associated with “an irregularity in the insertion of a specific glucose transporter (GLUT1) into the cell surface” of astrocytes.

“It could be more effective to direct therapeutic interventions at these events lying upstream of PHGDH or serine,” he concluded.

The study was partly supported by a Kreuger v. Wyeth research award. The investigators and Dr. Barger reported no conflicts of interest.

While previous research suggests that dietary supplementation with L-serine may be beneficial for patients with Alzheimer’s disease (AD), a new study cast doubt on the potential efficacy, and even the safety, of this treatment.

When given to patients with AD, L-serine supplements could be driving abnormally increased serine levels in the brain even higher, potentially accelerating neuronal death, according to study author Xu Chen, PhD, of the University of California, San Diego, and colleagues.

This conclusion conflicts with a 2020 study by Juliette Le Douce, PhD, and colleagues, who reported that oral L-serine supplementation may act as a “ready-to-use therapy” for AD, based on their findings that patients with AD had low levels of PHGDH, an enzyme necessary for synthesizing serine, and AD-like mice had low levels of serine.

Writing in Cell Metabolism, Dr. Chen and colleagues framed the present study, and their findings, in this context.

“In contrast to the work of Le Douce et al., here we report that PHGDH mRNA and protein levels are increased in the brains of two mouse models of AD and/or tauopathy, and are also progressively increased in human brains with no, early, and late AD pathology, as well as in people with no, asymptomatic, and symptomatic AD,” they wrote.

They suggested adjusting clinical recommendations for L-serine, the form of the amino acid commonly found in supplements. In the body, L-serine is converted to D-serine, which acts on the NMDA receptor (NMDAR).

‘Long-term use of D-serine contributes to neuronal death’ suggests research

“We feel oral L-serine as a ready-to-use therapy to AD warrants precaution,” Dr. Chen and colleagues wrote. “This is because despite being a cognitive enhancer, some [research] suggests that long-term use of D-serine contributes to neuronal death in AD through excitotoxicity. Furthermore, D-serine, as a co-agonist of NMDAR, would be expected to oppose NMDAR antagonists, which have proven clinical benefits in treating AD.”

According to principal author Sheng Zhong, PhD, of the University of California, San Diego, “Research is needed to test if targeting PHGDH can ameliorate cognitive decline in AD.”

Dr. Zhong also noted that the present findings support the “promise of using a specific RNA in blood as a biomarker for early detection of Alzheimer’s disease.” This approach is currently being validated at UCSD Shiley-Marcos Alzheimer’s Disease Research Center, he added.

Roles of PHGDH and serine in Alzheimer’s disease require further study

Commenting on both studies, Steve W. Barger, PhD, of the University of Arkansas for Medical Sciences, Little Rock, suggested that more work is needed to better understand the roles of PHGDH and serine in AD before clinical applications can be considered.

“In the end, these two studies fail to provide the clarity we need in designing evidence-based therapeutic hypotheses,” Dr. Barger said in an interview. “We still do not have a firm grasp on the role that D-serine plays in AD. Indeed, the evidence regarding even a single enzyme contributing to its levels is ambiguous.”

Dr. Barger, who has published extensively on the topic of neuronal death, with a particular focus on Alzheimer’s disease, noted that “determination of what happens to D-serine levels in AD has been of interest for decades,” but levels of the amino acid have been notoriously challenging to measure because “D-serine can disappear rapidly from the brain and its fluids after death.”

While Dr. Le Douce and colleagues did measure levels of serine in mice, Dr. Barger noted that the study by Dr. Chen and colleagues was conducted with more “quantitatively rigorous methods.” Even though Dr. Chen and colleagues “did not assay the levels of D-serine itself ... the implication of their findings is that PHGDH is poised to elevate this critical neurotransmitter,” leading to their conclusion that serine supplementation is “potentially dangerous.”

At this point, it may be too early to tell, according to Dr. Barger.

He suggested that conclusions drawn from PHGDH levels alone are “always limited,” and conclusions based on serine levels may be equally dubious, considering that the activities and effects of serine “are quite complex,” and may be influenced by other physiologic processes, including the effects of gut bacteria.

Instead, Dr. Barger suggested that changes in PHGDH and serine may be interpreted as signals coming from a more relevant process upstream: glucose metabolism.

“What we can say confidently is that the glucose metabolism that PHGDH connects to D-serine is most definitely a factor in AD,” he said. “Countless studies have documented what now appears to be a universal decline in glucose delivery to the cerebral cortex, even before frank dementia sets in.”

Dr. Barger noted that declining glucose delivery coincides with some of the earliest events in the development of AD, perhaps “linking accumulation of amyloid β-peptide to subsequent neurofibrillary tangles and tissue atrophy.”

Dr. Barger’s own work recently demonstrated that AD is associated with “an irregularity in the insertion of a specific glucose transporter (GLUT1) into the cell surface” of astrocytes.

“It could be more effective to direct therapeutic interventions at these events lying upstream of PHGDH or serine,” he concluded.

The study was partly supported by a Kreuger v. Wyeth research award. The investigators and Dr. Barger reported no conflicts of interest.

We have a half-forgotten Indian immigrant to thank – a hospital night porter turned biochemist –for revolutionizing treatment of leukemia, the once deadly childhood scourge that is still the most common pediatric cancer.

Dr. Yellapragada SubbaRow has been called the “father of chemotherapy” for developing methotrexate, a powerful, inexpensive therapy for leukemia and other diseases, and he is celebrated for additional scientific achievements. Yet Dr. SubbaRow’s life was marked more by struggle than glory.

1995 Indian stamp; photo in public domain

Born poor in southeastern India, he nearly succumbed to a tropical disease that killed two older brothers, and he didn’t focus on schoolwork until his father died. Later, prejudice dogged his years as an immigrant to the United States, and a blood clot took his life at the age of 53.

Scientifically, however, Dr. SubbaRow (pronounced sue-buh-rao) triumphed, despite mammoth challenges and a lack of recognition that persists to this day. National Cancer Research Month is a fitting time to look back on his extraordinary life and work and pay tribute to his accomplishments.
 

‘Yella,’ folic acid, and a paradigm shift

No one appreciates Dr. SubbaRow more than a cadre of Indian-born physicians who have kept his legacy alive in journal articles, presentations, and a Pulitzer Prize-winning book. Among them is author and oncologist Siddhartha Mukherjee, MD, who chronicled Dr. SubbaRow’s achievements in his New York Times No. 1 bestseller, “The Emperor of All Maladies: A Biography of Cancer.”

As Dr. Mukherjee wrote, Dr. SubbaRow was a “pioneer in many ways, a physician turned cellular physiologist, a chemist who had accidentally wandered into biology.” (Per Indian tradition, SubbaRow is the doctor’s first name, and Yellapragada is his surname, but medical literature uses SubbaRow as his cognomen, with some variations in spelling. Dr. Mukherjee wrote that his friends called him “Yella.”)

Dr. SubbaRow came to the United States in 1923, after enduring a difficult childhood and young adulthood. He’d survived bouts of religious fervor, childhood rebellion (including a bid to run away from home and become a banana trader), and a failed arranged marriage. His wife bore him a child who died in infancy. He left it all behind.

In Boston, medical officials rejected his degree. Broke, he worked for a time as a night porter at Brigham and Women’s Hospital in Boston, changing sheets and cleaning urinals. To a poor but proud high-caste Indian Brahmin, the culture shock of carrying out these tasks must have been especially jarring.

Dr. SubbaRow went on to earn a diploma from Harvard Medical School, also in Boston, and became a junior faculty member. As a foreigner, Dr. Mukherjee wrote, Dr. SubbaRow was a “reclusive, nocturnal, heavily accented vegetarian,” so different from his colleagues that advancement seemed impossible. Despite his pioneering biochemistry work, Harvard later declined to offer Dr. SubbaRow a tenured faculty position.

By the early 1940s, he took a job at an upstate New York pharmaceutical company called Lederle Labs (later purchased by Pfizer). At Lederle, Dr. SubbaRow strove to synthesize the vitamin known as folic acid. He ended up creating a kind of antivitamin, a lookalike that acted like folic acid but only succeeded in gumming up the works in receptors. But what good would it do to stop the body from absorbing folic acid? Plenty, it turned out.
 

Discoveries pile up, but credit and fame prove elusive

Dr. SubbaRow was no stranger to producing landmark biological work. He’d previously codiscovered phosphocreatine and ATP, which are crucial to muscular contractions. However, “in 1935, he had to disown the extent of his role in the discovery of the color test related to phosphorus, instead giving the credit to his co-author, who was being considered for promotion to a full professorship at Harvard,” wrote author Gerald Posner in his 2020 book, “Pharma: Greed, Lies and the Poisoning of America.”

Houston-area oncologist Kirtan Nautiyal, MD, who paid tribute to Dr. SubbaRow in a 2018 article, contended that “with his Indian instinct for self-effacement, he had irreparably sabotaged his own career.”

Dr. SubbaRow and his team also developed “the first effective treatment of filariasis, which causes elephantiasis of the lower limbs and genitals in millions of people, mainly in tropical countries,” Dr. Nautiyal wrote. “Later in the decade, his antibiotic program generated polymyxin, the first effective treatment against the class of bacteria called Gram negatives, and aureomycin, the first “broad-spectrum’ antibiotic.” (Aureomycin is also the first tetracycline antibiotic.)

Dr. SubbaRow’s discovery of a folic acid antagonist would again go largely unheralded. But first came the realization that folic acid made childhood leukemia worse, not better, and the prospect that this process could potentially be reversed.
 

Rise of methotrexate and fall of leukemia

In Boston, Sidney Farber, MD, a Boston pathologist, was desperate to help Robert Sandler, a 2-year-old leukemia patient. Dr. Farber contacted his ex-colleague Dr. SubbaRow to request a supply of aminopterin, an early version of methotrexate that Dr. SubbaRow and his team had developed. Dr. Farber injected Robert with the substance and within 3 days, the toddler’s white blood count started falling – fast. He stopped bleeding, resumed eating, and once again seemed almost identical to his twin brother, as Dr. Mukherjee wrote in his book.

Leukemia had never gone into remission before. Unfortunately, the treatment only worked temporarily. Robert, like other children treated with the drug, relapsed and died within months. But Dr. Farber “saw a door open” – a chemical, a kind of chemotherapy, that could turn back cancer. In the case of folic acid antagonists, they do so by stopping cancer cells from replicating.

Methotrexate, a related agent synthesized by Dr. SubbaRow, would become a mainstay of leukemia treatment and begin to produce long-term remission from acute lymphoblastic leukemia in 1970, when combination chemotherapy was developed.

Other cancers fell to methotrexate treatment. “Previous assumptions that cancer was nearly always fatal were revised, and the field of medical oncology (treatment of cancer with chemotherapy), which had not previously existed, was formally established in 1971,” according to the National Cancer Institute’s history of methotrexate. This account does not mention Dr. SubbaRow.
 

Death takes the doctor, but his legacy remains

In biographies, as well as his own words, Dr. SubbaRow comes across as a prickly, hard-driving workaholic who had little interest in intimate human connections. “It is not good to ask in every letter when I will be back,” he wrote to his wife back in India, before cutting off ties completely in the early 1930s. “I will come as early as possible. ... I do not want to write anything more.”

It seems, as his biographer S.P.K. Gupta noted, that “he was quite determined that the time allotted to him on Earth should be completely devoted to finding cures for ailments that plagued mankind.”

Still, Dr. SubbaRow’s research team was devoted to him, and he had plenty of reasons to be bitter, such as the prejudice and isolation he encountered in the United States and earlier, in British-run India. According to Mr. Posner’s book, even as a young medical student, Dr. SubbaRow heeded the call of Indian independence activist Mohandas Gandhi. He “refused the British surgical gown given him at school and instead donned a traditional and simple cotton Khadi. That act of defiance cost SubbaRow the college degree that was necessary for him to get into the State Medical College.”

During the last year of his life, Dr. SubbaRow faced yet another humiliation: In his landmark 1948 study about aminopterin as a treatment for leukemia, his colleague Dr. Farber failed to credit him, an “astonishing omission” as Yaddanapudi Ravindranath, MBBS, a pediatric hematologist/oncologist at Wayne State University, Detroit, put it. “From everything I know, Dr. Farber spent the rest of his career apologizing and trying to make amends for it,” Dr. Ravindranath said in an interview.
 

A career cut short, and a lasting legacy

In 1948, at the age of 53, Dr. SubbaRow suddenly died. “Many think Dr. SubbaRow would have won [the] Nobel Prize had he lived a few years longer,” said Dr. Ravindranath.

Like Dr. SubbaRow, Dr. Ravindranath was born in Andhra Pradesh state, near the city of Chennai formerly known as Madras. “Being a compatriot, in a way I continue his legacy, and I am obviously proud of him,” said Dr. Ravindranath, who has conducted his own landmark research regarding methotrexate and leukemia.

Nearly 75 years after Dr. SubbaRow’s death, Indian-born physicians like Dr. Ravindranath continue to honor him in print, trying to ensure that he’s not forgotten. Methotrexate remains a crucial treatment for leukemia, along with a long list of other ailments, including psoriasis.

Recognition for “Yella” may have come late and infrequently, but a Lederle Laboratories research library named after him offered Dr. SubbaRow a kind of immortality. A plaque there memorialized him in stone as a scientist, teacher, philosopher, and humanitarian, featuring the quote: “Science simply prolongs life. Religion deepens it.”

By all accounts, Dr. SubbaRow was a man of science and faith who had faith in science.

We have a half-forgotten Indian immigrant to thank – a hospital night porter turned biochemist –for revolutionizing treatment of leukemia, the once deadly childhood scourge that is still the most common pediatric cancer.

Dr. Yellapragada SubbaRow has been called the “father of chemotherapy” for developing methotrexate, a powerful, inexpensive therapy for leukemia and other diseases, and he is celebrated for additional scientific achievements. Yet Dr. SubbaRow’s life was marked more by struggle than glory.

1995 Indian stamp; photo in public domain

Born poor in southeastern India, he nearly succumbed to a tropical disease that killed two older brothers, and he didn’t focus on schoolwork until his father died. Later, prejudice dogged his years as an immigrant to the United States, and a blood clot took his life at the age of 53.

Scientifically, however, Dr. SubbaRow (pronounced sue-buh-rao) triumphed, despite mammoth challenges and a lack of recognition that persists to this day. National Cancer Research Month is a fitting time to look back on his extraordinary life and work and pay tribute to his accomplishments.
 

‘Yella,’ folic acid, and a paradigm shift

No one appreciates Dr. SubbaRow more than a cadre of Indian-born physicians who have kept his legacy alive in journal articles, presentations, and a Pulitzer Prize-winning book. Among them is author and oncologist Siddhartha Mukherjee, MD, who chronicled Dr. SubbaRow’s achievements in his New York Times No. 1 bestseller, “The Emperor of All Maladies: A Biography of Cancer.”

As Dr. Mukherjee wrote, Dr. SubbaRow was a “pioneer in many ways, a physician turned cellular physiologist, a chemist who had accidentally wandered into biology.” (Per Indian tradition, SubbaRow is the doctor’s first name, and Yellapragada is his surname, but medical literature uses SubbaRow as his cognomen, with some variations in spelling. Dr. Mukherjee wrote that his friends called him “Yella.”)

Dr. SubbaRow came to the United States in 1923, after enduring a difficult childhood and young adulthood. He’d survived bouts of religious fervor, childhood rebellion (including a bid to run away from home and become a banana trader), and a failed arranged marriage. His wife bore him a child who died in infancy. He left it all behind.

In Boston, medical officials rejected his degree. Broke, he worked for a time as a night porter at Brigham and Women’s Hospital in Boston, changing sheets and cleaning urinals. To a poor but proud high-caste Indian Brahmin, the culture shock of carrying out these tasks must have been especially jarring.

Dr. SubbaRow went on to earn a diploma from Harvard Medical School, also in Boston, and became a junior faculty member. As a foreigner, Dr. Mukherjee wrote, Dr. SubbaRow was a “reclusive, nocturnal, heavily accented vegetarian,” so different from his colleagues that advancement seemed impossible. Despite his pioneering biochemistry work, Harvard later declined to offer Dr. SubbaRow a tenured faculty position.

By the early 1940s, he took a job at an upstate New York pharmaceutical company called Lederle Labs (later purchased by Pfizer). At Lederle, Dr. SubbaRow strove to synthesize the vitamin known as folic acid. He ended up creating a kind of antivitamin, a lookalike that acted like folic acid but only succeeded in gumming up the works in receptors. But what good would it do to stop the body from absorbing folic acid? Plenty, it turned out.
 

Discoveries pile up, but credit and fame prove elusive

Dr. SubbaRow was no stranger to producing landmark biological work. He’d previously codiscovered phosphocreatine and ATP, which are crucial to muscular contractions. However, “in 1935, he had to disown the extent of his role in the discovery of the color test related to phosphorus, instead giving the credit to his co-author, who was being considered for promotion to a full professorship at Harvard,” wrote author Gerald Posner in his 2020 book, “Pharma: Greed, Lies and the Poisoning of America.”

Houston-area oncologist Kirtan Nautiyal, MD, who paid tribute to Dr. SubbaRow in a 2018 article, contended that “with his Indian instinct for self-effacement, he had irreparably sabotaged his own career.”

Dr. SubbaRow and his team also developed “the first effective treatment of filariasis, which causes elephantiasis of the lower limbs and genitals in millions of people, mainly in tropical countries,” Dr. Nautiyal wrote. “Later in the decade, his antibiotic program generated polymyxin, the first effective treatment against the class of bacteria called Gram negatives, and aureomycin, the first “broad-spectrum’ antibiotic.” (Aureomycin is also the first tetracycline antibiotic.)

Dr. SubbaRow’s discovery of a folic acid antagonist would again go largely unheralded. But first came the realization that folic acid made childhood leukemia worse, not better, and the prospect that this process could potentially be reversed.
 

Rise of methotrexate and fall of leukemia

In Boston, Sidney Farber, MD, a Boston pathologist, was desperate to help Robert Sandler, a 2-year-old leukemia patient. Dr. Farber contacted his ex-colleague Dr. SubbaRow to request a supply of aminopterin, an early version of methotrexate that Dr. SubbaRow and his team had developed. Dr. Farber injected Robert with the substance and within 3 days, the toddler’s white blood count started falling – fast. He stopped bleeding, resumed eating, and once again seemed almost identical to his twin brother, as Dr. Mukherjee wrote in his book.

Leukemia had never gone into remission before. Unfortunately, the treatment only worked temporarily. Robert, like other children treated with the drug, relapsed and died within months. But Dr. Farber “saw a door open” – a chemical, a kind of chemotherapy, that could turn back cancer. In the case of folic acid antagonists, they do so by stopping cancer cells from replicating.

Methotrexate, a related agent synthesized by Dr. SubbaRow, would become a mainstay of leukemia treatment and begin to produce long-term remission from acute lymphoblastic leukemia in 1970, when combination chemotherapy was developed.

Other cancers fell to methotrexate treatment. “Previous assumptions that cancer was nearly always fatal were revised, and the field of medical oncology (treatment of cancer with chemotherapy), which had not previously existed, was formally established in 1971,” according to the National Cancer Institute’s history of methotrexate. This account does not mention Dr. SubbaRow.
 

Death takes the doctor, but his legacy remains

In biographies, as well as his own words, Dr. SubbaRow comes across as a prickly, hard-driving workaholic who had little interest in intimate human connections. “It is not good to ask in every letter when I will be back,” he wrote to his wife back in India, before cutting off ties completely in the early 1930s. “I will come as early as possible. ... I do not want to write anything more.”

It seems, as his biographer S.P.K. Gupta noted, that “he was quite determined that the time allotted to him on Earth should be completely devoted to finding cures for ailments that plagued mankind.”

Still, Dr. SubbaRow’s research team was devoted to him, and he had plenty of reasons to be bitter, such as the prejudice and isolation he encountered in the United States and earlier, in British-run India. According to Mr. Posner’s book, even as a young medical student, Dr. SubbaRow heeded the call of Indian independence activist Mohandas Gandhi. He “refused the British surgical gown given him at school and instead donned a traditional and simple cotton Khadi. That act of defiance cost SubbaRow the college degree that was necessary for him to get into the State Medical College.”

During the last year of his life, Dr. SubbaRow faced yet another humiliation: In his landmark 1948 study about aminopterin as a treatment for leukemia, his colleague Dr. Farber failed to credit him, an “astonishing omission” as Yaddanapudi Ravindranath, MBBS, a pediatric hematologist/oncologist at Wayne State University, Detroit, put it. “From everything I know, Dr. Farber spent the rest of his career apologizing and trying to make amends for it,” Dr. Ravindranath said in an interview.
 

A career cut short, and a lasting legacy

In 1948, at the age of 53, Dr. SubbaRow suddenly died. “Many think Dr. SubbaRow would have won [the] Nobel Prize had he lived a few years longer,” said Dr. Ravindranath.

Like Dr. SubbaRow, Dr. Ravindranath was born in Andhra Pradesh state, near the city of Chennai formerly known as Madras. “Being a compatriot, in a way I continue his legacy, and I am obviously proud of him,” said Dr. Ravindranath, who has conducted his own landmark research regarding methotrexate and leukemia.

Nearly 75 years after Dr. SubbaRow’s death, Indian-born physicians like Dr. Ravindranath continue to honor him in print, trying to ensure that he’s not forgotten. Methotrexate remains a crucial treatment for leukemia, along with a long list of other ailments, including psoriasis.

Recognition for “Yella” may have come late and infrequently, but a Lederle Laboratories research library named after him offered Dr. SubbaRow a kind of immortality. A plaque there memorialized him in stone as a scientist, teacher, philosopher, and humanitarian, featuring the quote: “Science simply prolongs life. Religion deepens it.”

By all accounts, Dr. SubbaRow was a man of science and faith who had faith in science.

We have a half-forgotten Indian immigrant to thank – a hospital night porter turned biochemist –for revolutionizing treatment of leukemia, the once deadly childhood scourge that is still the most common pediatric cancer.

Dr. Yellapragada SubbaRow has been called the “father of chemotherapy” for developing methotrexate, a powerful, inexpensive therapy for leukemia and other diseases, and he is celebrated for additional scientific achievements. Yet Dr. SubbaRow’s life was marked more by struggle than glory.

1995 Indian stamp; photo in public domain

Born poor in southeastern India, he nearly succumbed to a tropical disease that killed two older brothers, and he didn’t focus on schoolwork until his father died. Later, prejudice dogged his years as an immigrant to the United States, and a blood clot took his life at the age of 53.

Scientifically, however, Dr. SubbaRow (pronounced sue-buh-rao) triumphed, despite mammoth challenges and a lack of recognition that persists to this day. National Cancer Research Month is a fitting time to look back on his extraordinary life and work and pay tribute to his accomplishments.
 

‘Yella,’ folic acid, and a paradigm shift

No one appreciates Dr. SubbaRow more than a cadre of Indian-born physicians who have kept his legacy alive in journal articles, presentations, and a Pulitzer Prize-winning book. Among them is author and oncologist Siddhartha Mukherjee, MD, who chronicled Dr. SubbaRow’s achievements in his New York Times No. 1 bestseller, “The Emperor of All Maladies: A Biography of Cancer.”

As Dr. Mukherjee wrote, Dr. SubbaRow was a “pioneer in many ways, a physician turned cellular physiologist, a chemist who had accidentally wandered into biology.” (Per Indian tradition, SubbaRow is the doctor’s first name, and Yellapragada is his surname, but medical literature uses SubbaRow as his cognomen, with some variations in spelling. Dr. Mukherjee wrote that his friends called him “Yella.”)

Dr. SubbaRow came to the United States in 1923, after enduring a difficult childhood and young adulthood. He’d survived bouts of religious fervor, childhood rebellion (including a bid to run away from home and become a banana trader), and a failed arranged marriage. His wife bore him a child who died in infancy. He left it all behind.

In Boston, medical officials rejected his degree. Broke, he worked for a time as a night porter at Brigham and Women’s Hospital in Boston, changing sheets and cleaning urinals. To a poor but proud high-caste Indian Brahmin, the culture shock of carrying out these tasks must have been especially jarring.

Dr. SubbaRow went on to earn a diploma from Harvard Medical School, also in Boston, and became a junior faculty member. As a foreigner, Dr. Mukherjee wrote, Dr. SubbaRow was a “reclusive, nocturnal, heavily accented vegetarian,” so different from his colleagues that advancement seemed impossible. Despite his pioneering biochemistry work, Harvard later declined to offer Dr. SubbaRow a tenured faculty position.

By the early 1940s, he took a job at an upstate New York pharmaceutical company called Lederle Labs (later purchased by Pfizer). At Lederle, Dr. SubbaRow strove to synthesize the vitamin known as folic acid. He ended up creating a kind of antivitamin, a lookalike that acted like folic acid but only succeeded in gumming up the works in receptors. But what good would it do to stop the body from absorbing folic acid? Plenty, it turned out.
 

Discoveries pile up, but credit and fame prove elusive

Dr. SubbaRow was no stranger to producing landmark biological work. He’d previously codiscovered phosphocreatine and ATP, which are crucial to muscular contractions. However, “in 1935, he had to disown the extent of his role in the discovery of the color test related to phosphorus, instead giving the credit to his co-author, who was being considered for promotion to a full professorship at Harvard,” wrote author Gerald Posner in his 2020 book, “Pharma: Greed, Lies and the Poisoning of America.”

Houston-area oncologist Kirtan Nautiyal, MD, who paid tribute to Dr. SubbaRow in a 2018 article, contended that “with his Indian instinct for self-effacement, he had irreparably sabotaged his own career.”

Dr. SubbaRow and his team also developed “the first effective treatment of filariasis, which causes elephantiasis of the lower limbs and genitals in millions of people, mainly in tropical countries,” Dr. Nautiyal wrote. “Later in the decade, his antibiotic program generated polymyxin, the first effective treatment against the class of bacteria called Gram negatives, and aureomycin, the first “broad-spectrum’ antibiotic.” (Aureomycin is also the first tetracycline antibiotic.)

Dr. SubbaRow’s discovery of a folic acid antagonist would again go largely unheralded. But first came the realization that folic acid made childhood leukemia worse, not better, and the prospect that this process could potentially be reversed.
 

Rise of methotrexate and fall of leukemia

In Boston, Sidney Farber, MD, a Boston pathologist, was desperate to help Robert Sandler, a 2-year-old leukemia patient. Dr. Farber contacted his ex-colleague Dr. SubbaRow to request a supply of aminopterin, an early version of methotrexate that Dr. SubbaRow and his team had developed. Dr. Farber injected Robert with the substance and within 3 days, the toddler’s white blood count started falling – fast. He stopped bleeding, resumed eating, and once again seemed almost identical to his twin brother, as Dr. Mukherjee wrote in his book.

Leukemia had never gone into remission before. Unfortunately, the treatment only worked temporarily. Robert, like other children treated with the drug, relapsed and died within months. But Dr. Farber “saw a door open” – a chemical, a kind of chemotherapy, that could turn back cancer. In the case of folic acid antagonists, they do so by stopping cancer cells from replicating.

Methotrexate, a related agent synthesized by Dr. SubbaRow, would become a mainstay of leukemia treatment and begin to produce long-term remission from acute lymphoblastic leukemia in 1970, when combination chemotherapy was developed.

Other cancers fell to methotrexate treatment. “Previous assumptions that cancer was nearly always fatal were revised, and the field of medical oncology (treatment of cancer with chemotherapy), which had not previously existed, was formally established in 1971,” according to the National Cancer Institute’s history of methotrexate. This account does not mention Dr. SubbaRow.
 

Death takes the doctor, but his legacy remains

In biographies, as well as his own words, Dr. SubbaRow comes across as a prickly, hard-driving workaholic who had little interest in intimate human connections. “It is not good to ask in every letter when I will be back,” he wrote to his wife back in India, before cutting off ties completely in the early 1930s. “I will come as early as possible. ... I do not want to write anything more.”

It seems, as his biographer S.P.K. Gupta noted, that “he was quite determined that the time allotted to him on Earth should be completely devoted to finding cures for ailments that plagued mankind.”

Still, Dr. SubbaRow’s research team was devoted to him, and he had plenty of reasons to be bitter, such as the prejudice and isolation he encountered in the United States and earlier, in British-run India. According to Mr. Posner’s book, even as a young medical student, Dr. SubbaRow heeded the call of Indian independence activist Mohandas Gandhi. He “refused the British surgical gown given him at school and instead donned a traditional and simple cotton Khadi. That act of defiance cost SubbaRow the college degree that was necessary for him to get into the State Medical College.”

During the last year of his life, Dr. SubbaRow faced yet another humiliation: In his landmark 1948 study about aminopterin as a treatment for leukemia, his colleague Dr. Farber failed to credit him, an “astonishing omission” as Yaddanapudi Ravindranath, MBBS, a pediatric hematologist/oncologist at Wayne State University, Detroit, put it. “From everything I know, Dr. Farber spent the rest of his career apologizing and trying to make amends for it,” Dr. Ravindranath said in an interview.
 

A career cut short, and a lasting legacy

In 1948, at the age of 53, Dr. SubbaRow suddenly died. “Many think Dr. SubbaRow would have won [the] Nobel Prize had he lived a few years longer,” said Dr. Ravindranath.

Like Dr. SubbaRow, Dr. Ravindranath was born in Andhra Pradesh state, near the city of Chennai formerly known as Madras. “Being a compatriot, in a way I continue his legacy, and I am obviously proud of him,” said Dr. Ravindranath, who has conducted his own landmark research regarding methotrexate and leukemia.

Nearly 75 years after Dr. SubbaRow’s death, Indian-born physicians like Dr. Ravindranath continue to honor him in print, trying to ensure that he’s not forgotten. Methotrexate remains a crucial treatment for leukemia, along with a long list of other ailments, including psoriasis.

Recognition for “Yella” may have come late and infrequently, but a Lederle Laboratories research library named after him offered Dr. SubbaRow a kind of immortality. A plaque there memorialized him in stone as a scientist, teacher, philosopher, and humanitarian, featuring the quote: “Science simply prolongs life. Religion deepens it.”

By all accounts, Dr. SubbaRow was a man of science and faith who had faith in science.

A recent article on Medscape entitled “Online Reviews Most Important Factor in Choosing a Doctor: Survey” really got me thinking about my online presence. According to the results of a new Press Ganey survey, online reviews and star ratings are the most important factor for consumers when choosing a new health care provider, even more so than the recommendation of another doctor. Almost 85% of the survey respondents said they wouldn’t make an appointment with a referred provider if they had a rating of less than 4 stars.

To be honest, I’ve rarely thought about my ratings or online reviews, and I almost never enter my own name into a web browser to see what might emerge. I don’t use most popular social media apps, I don’t have a professional website, and I was completely late in joining LinkedIn. After considering the Press Ganey survey results, though, I’m wondering how many patients (or potential patients) have found me online. And what exactly did they see?

So, I just searched online for my ratings and reviews. There weren’t many direct hits (although I’m not sure if that is a good thing or not). One of the results listed me as a “Fibromyalgia Doctor” at www.lymeforums.org. To be clear, I’m a locum tenens infectious diseases provider with a focus on inpatient consultations and teaching. I couldn’t find any reviews for myself on WebMD, but I had one rating on the Healthgrades website – I was pleased to see someone gave me 5 stars (though there weren’t any comments) until I realized the site listed my address at an ob.gyn. office; I’m not even sure if that rating was meant for me.

Use of the Internet to assess my qualities as a physician is clearly limited, and much of the online information about my specialty and practice sites is completely inaccurate. Yet, according to the Press Ganey survey, the average consumer uses three different websites and reads more than five online reviews before making a provider decision. Once they’ve seen a provider, though, patients rank practice customer service and communication as more important than “bedside manner” when considering a 5-star review. So, it appears that many physician reviews and ratings probably reflect the performance of the office staff, not the provider.

Given the few hits that I encountered when searching my own name, I’m not convinced I need to do anything differently about my online presence; essentially, I don’t really have one. However, there were certainly a lot of other physicians with the same last name as mine who did have impressive numbers of reviews and ratings. One doctor of cosmetic surgery had more than 200 reviews on multiple sites; almost all were positive, but a few patients rated him at 1 or 2 (out of 5) stars, suggesting that patients should find a new surgeon. What does one do about those outliers?

Medicine is indeed a business and patients behave as consumers when searching the web for a health care provider. Another survey has suggested that just one negative review may cause a business to risk losing 22% of its customers, and that multiple bad ratings are even worse – nearly 60% of customers will avoid a business with three or more negative online reviews.

A few years ago, The Washington Post published an article about doctors who were fighting back against bad reviews. Unfortunately, while trying to directly combat inaccuracies, some providers divulged sensitive patient information and suffered the consequences of HIPAA violations. Many legal experts suggest that, in most cases, physicians should restrain from responding publicly to negative online reviews, however tempting it may be to react.

If a negative review is attributed to a specific patient, some lawyers recommend contacting them privately by phone to address their concerns; this may clear the air enough to result in a withdrawal of the negative review or rating. Flagging and reporting fake or unsubstantiated negative reviews (or reviews that violate the Terms of Service of a specific platform) can be done. Consultation with an Internet defamation attorney might be helpful in some circumstances, though hopefully, legal action such as a lawsuit or a cease-and-desist letter can be avoided.

For physicians who do maintain an online presence, engaging with an online reputation management service can help suppress fake or negative reviews while offering strategies for building a better reputation. As for me, I think that I’m grateful my name hasn’t attracted a lot of attention at physician ranking and review sites. I guess we’ll see if it stays that way.

Dr. Devlin is president of Locum Infectious Disease Services, and an independent contractor for Weatherby Healthcare. She has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

A recent article on Medscape entitled “Online Reviews Most Important Factor in Choosing a Doctor: Survey” really got me thinking about my online presence. According to the results of a new Press Ganey survey, online reviews and star ratings are the most important factor for consumers when choosing a new health care provider, even more so than the recommendation of another doctor. Almost 85% of the survey respondents said they wouldn’t make an appointment with a referred provider if they had a rating of less than 4 stars.

To be honest, I’ve rarely thought about my ratings or online reviews, and I almost never enter my own name into a web browser to see what might emerge. I don’t use most popular social media apps, I don’t have a professional website, and I was completely late in joining LinkedIn. After considering the Press Ganey survey results, though, I’m wondering how many patients (or potential patients) have found me online. And what exactly did they see?

So, I just searched online for my ratings and reviews. There weren’t many direct hits (although I’m not sure if that is a good thing or not). One of the results listed me as a “Fibromyalgia Doctor” at www.lymeforums.org. To be clear, I’m a locum tenens infectious diseases provider with a focus on inpatient consultations and teaching. I couldn’t find any reviews for myself on WebMD, but I had one rating on the Healthgrades website – I was pleased to see someone gave me 5 stars (though there weren’t any comments) until I realized the site listed my address at an ob.gyn. office; I’m not even sure if that rating was meant for me.

Use of the Internet to assess my qualities as a physician is clearly limited, and much of the online information about my specialty and practice sites is completely inaccurate. Yet, according to the Press Ganey survey, the average consumer uses three different websites and reads more than five online reviews before making a provider decision. Once they’ve seen a provider, though, patients rank practice customer service and communication as more important than “bedside manner” when considering a 5-star review. So, it appears that many physician reviews and ratings probably reflect the performance of the office staff, not the provider.

Given the few hits that I encountered when searching my own name, I’m not convinced I need to do anything differently about my online presence; essentially, I don’t really have one. However, there were certainly a lot of other physicians with the same last name as mine who did have impressive numbers of reviews and ratings. One doctor of cosmetic surgery had more than 200 reviews on multiple sites; almost all were positive, but a few patients rated him at 1 or 2 (out of 5) stars, suggesting that patients should find a new surgeon. What does one do about those outliers?

Medicine is indeed a business and patients behave as consumers when searching the web for a health care provider. Another survey has suggested that just one negative review may cause a business to risk losing 22% of its customers, and that multiple bad ratings are even worse – nearly 60% of customers will avoid a business with three or more negative online reviews.

A few years ago, The Washington Post published an article about doctors who were fighting back against bad reviews. Unfortunately, while trying to directly combat inaccuracies, some providers divulged sensitive patient information and suffered the consequences of HIPAA violations. Many legal experts suggest that, in most cases, physicians should restrain from responding publicly to negative online reviews, however tempting it may be to react.

If a negative review is attributed to a specific patient, some lawyers recommend contacting them privately by phone to address their concerns; this may clear the air enough to result in a withdrawal of the negative review or rating. Flagging and reporting fake or unsubstantiated negative reviews (or reviews that violate the Terms of Service of a specific platform) can be done. Consultation with an Internet defamation attorney might be helpful in some circumstances, though hopefully, legal action such as a lawsuit or a cease-and-desist letter can be avoided.

For physicians who do maintain an online presence, engaging with an online reputation management service can help suppress fake or negative reviews while offering strategies for building a better reputation. As for me, I think that I’m grateful my name hasn’t attracted a lot of attention at physician ranking and review sites. I guess we’ll see if it stays that way.

Dr. Devlin is president of Locum Infectious Disease Services, and an independent contractor for Weatherby Healthcare. She has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

A recent article on Medscape entitled “Online Reviews Most Important Factor in Choosing a Doctor: Survey” really got me thinking about my online presence. According to the results of a new Press Ganey survey, online reviews and star ratings are the most important factor for consumers when choosing a new health care provider, even more so than the recommendation of another doctor. Almost 85% of the survey respondents said they wouldn’t make an appointment with a referred provider if they had a rating of less than 4 stars.

To be honest, I’ve rarely thought about my ratings or online reviews, and I almost never enter my own name into a web browser to see what might emerge. I don’t use most popular social media apps, I don’t have a professional website, and I was completely late in joining LinkedIn. After considering the Press Ganey survey results, though, I’m wondering how many patients (or potential patients) have found me online. And what exactly did they see?

So, I just searched online for my ratings and reviews. There weren’t many direct hits (although I’m not sure if that is a good thing or not). One of the results listed me as a “Fibromyalgia Doctor” at www.lymeforums.org. To be clear, I’m a locum tenens infectious diseases provider with a focus on inpatient consultations and teaching. I couldn’t find any reviews for myself on WebMD, but I had one rating on the Healthgrades website – I was pleased to see someone gave me 5 stars (though there weren’t any comments) until I realized the site listed my address at an ob.gyn. office; I’m not even sure if that rating was meant for me.

Use of the Internet to assess my qualities as a physician is clearly limited, and much of the online information about my specialty and practice sites is completely inaccurate. Yet, according to the Press Ganey survey, the average consumer uses three different websites and reads more than five online reviews before making a provider decision. Once they’ve seen a provider, though, patients rank practice customer service and communication as more important than “bedside manner” when considering a 5-star review. So, it appears that many physician reviews and ratings probably reflect the performance of the office staff, not the provider.

Given the few hits that I encountered when searching my own name, I’m not convinced I need to do anything differently about my online presence; essentially, I don’t really have one. However, there were certainly a lot of other physicians with the same last name as mine who did have impressive numbers of reviews and ratings. One doctor of cosmetic surgery had more than 200 reviews on multiple sites; almost all were positive, but a few patients rated him at 1 or 2 (out of 5) stars, suggesting that patients should find a new surgeon. What does one do about those outliers?

Medicine is indeed a business and patients behave as consumers when searching the web for a health care provider. Another survey has suggested that just one negative review may cause a business to risk losing 22% of its customers, and that multiple bad ratings are even worse – nearly 60% of customers will avoid a business with three or more negative online reviews.

A few years ago, The Washington Post published an article about doctors who were fighting back against bad reviews. Unfortunately, while trying to directly combat inaccuracies, some providers divulged sensitive patient information and suffered the consequences of HIPAA violations. Many legal experts suggest that, in most cases, physicians should restrain from responding publicly to negative online reviews, however tempting it may be to react.

If a negative review is attributed to a specific patient, some lawyers recommend contacting them privately by phone to address their concerns; this may clear the air enough to result in a withdrawal of the negative review or rating. Flagging and reporting fake or unsubstantiated negative reviews (or reviews that violate the Terms of Service of a specific platform) can be done. Consultation with an Internet defamation attorney might be helpful in some circumstances, though hopefully, legal action such as a lawsuit or a cease-and-desist letter can be avoided.

For physicians who do maintain an online presence, engaging with an online reputation management service can help suppress fake or negative reviews while offering strategies for building a better reputation. As for me, I think that I’m grateful my name hasn’t attracted a lot of attention at physician ranking and review sites. I guess we’ll see if it stays that way.

Dr. Devlin is president of Locum Infectious Disease Services, and an independent contractor for Weatherby Healthcare. She has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

New data present further evidence that SARS-CoV-2 infection can settle in the gastrointestinal tract and that it can persist long after the infection has cleared the lungs.

Infection of the GI tract may figure prominently in long COVID, the study authors suggested.

Led by Aravind Natarajan, PhD, with the departments of genetics and medicine at Stanford (Calif.) University, they analyzed fecal RNA shedding up to 10 months after a COVID-19 diagnosis in 673 stool samples from 113 patients with mild to moderate disease.

They found that, in the week after diagnosis, COVID RNA remnants were present in the stool of approximately half (49.2%) of the patients. Seven months later, about 4% of them shed fecal viral RNA.

The authors noted that there was no ongoing SARS-CoV-2 RNA shedding in respiratory samples of patients at the 4-month mark.

Using self-reported symptoms regularly collected by questionnaire, they also found a correlation of long-term fecal shedding of SARS-CoV-2 RNA with abdominal pain, nausea, and vomiting.

The findings were published online in Med.
 

Implications of long-term viral shedding

Previous studies have found SARS-CoV-2 RNA in respiratory and fecal samples and have documented viral replication in lung and intestinal tissue. But before the current study, little had been known about long-term shedding, especially in those who have mild COVID. Most studies of viral shedding have been with severe COVID cases.

The authors noted that most studies of this kind are cross-sectional. The few other longitudinal studies have focused on early time points just after diagnosis.

Senior author Ami S. Bhatt, MD, associate professor in the departments of medicine and hematology at Stanford University, said in an interview that, though the viral genetic material in the feces lingers, on the basis of available evidence, it is highly unlikely to be contagious in most cases.

She said that understanding the dynamics of fecal shedding of SARS-CoV-2 genetic material will help interpret wastewater-based studies that are trying to determine population prevalence of the virus.

“While we don’t know the exact clinical importance of the longer-term shedding of SARS-CoV-2 in individuals with COVID-19, some have speculated that those who have long-term shedding of SARS-CoV-2 may have ongoing infections that might benefit from treatment,” she said.

“Our data support the idea that the long-term GI-related symptoms in some people might be the consequence of an ongoing infection in the GI tract, even after the respiratory infection has cleared,” Dr. Bhatt said.

“Alternatively, the presence of ongoing viral genetic material in the gut might be a trigger for the immune system to continually be active against the virus, and our immune system reaction may be the reason for long COVID–type symptoms,” she added. “This area is ripe for additional studies.”

Dr. Bhatt and colleagues will continue studying viral shedding in fecal samples as part of the nationwide RECOVER Initiative.

When reached for comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview that previous studies have indicated that the virus may be detected in the stool for a month or more and for about 2 weeks on average. Whether the virus is infectious has been in question.

But it’s not so much that the virus is infectious in the GI tract and causing symptoms, he said. Rather, there are biomic changes related to COVID, including a loss of diversity in the gut bacteria, which disrupts the balance.

“This may actually in some way predispose some patients to impaired clearance of their symptoms,” Dr. Johnson explained. “There seems to be a growing recognition that this entity called long-haul COVID may be related to specific bacterial disruptions, and the more rapidly you can resolve these disruptions, the less likely you are to continue with long-haul symptoms.”

He said that, among people who have mild COVID, the virus typically clears and gut bacteria return to normal. With severe or persistent illness, gut dysbiosis persists, he said.

“People need to be aware that the GI tract is involved in a sizable percent of patients with COVID,” Dr. Johnson said. “The GI-tract testing may reflect that the virus is there, but persistence of the detectable test positivity is very unlikely to reflect active virus.”

The authors noted that they collected only six samples from the participants over the 10-month study period.

“Follow-up studies with more frequent sampling, especially in the first 2 months after diagnosis, may help build a more nuanced model of decline of fecal viral RNA concentration over time,” they wrote.

The study was supported by a Stanford ChemH-IMA grant, fellowships from the AACR and the National Science Foundation, and the National Institutes of Health. The authors and Dr. Johnson reported no relevant financial relationships. Dr. Johnson is a regular contributor to this news organization.

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

New data present further evidence that SARS-CoV-2 infection can settle in the gastrointestinal tract and that it can persist long after the infection has cleared the lungs.

Infection of the GI tract may figure prominently in long COVID, the study authors suggested.

Led by Aravind Natarajan, PhD, with the departments of genetics and medicine at Stanford (Calif.) University, they analyzed fecal RNA shedding up to 10 months after a COVID-19 diagnosis in 673 stool samples from 113 patients with mild to moderate disease.

They found that, in the week after diagnosis, COVID RNA remnants were present in the stool of approximately half (49.2%) of the patients. Seven months later, about 4% of them shed fecal viral RNA.

The authors noted that there was no ongoing SARS-CoV-2 RNA shedding in respiratory samples of patients at the 4-month mark.

Using self-reported symptoms regularly collected by questionnaire, they also found a correlation of long-term fecal shedding of SARS-CoV-2 RNA with abdominal pain, nausea, and vomiting.

The findings were published online in Med.
 

Implications of long-term viral shedding

Previous studies have found SARS-CoV-2 RNA in respiratory and fecal samples and have documented viral replication in lung and intestinal tissue. But before the current study, little had been known about long-term shedding, especially in those who have mild COVID. Most studies of viral shedding have been with severe COVID cases.

The authors noted that most studies of this kind are cross-sectional. The few other longitudinal studies have focused on early time points just after diagnosis.

Senior author Ami S. Bhatt, MD, associate professor in the departments of medicine and hematology at Stanford University, said in an interview that, though the viral genetic material in the feces lingers, on the basis of available evidence, it is highly unlikely to be contagious in most cases.

She said that understanding the dynamics of fecal shedding of SARS-CoV-2 genetic material will help interpret wastewater-based studies that are trying to determine population prevalence of the virus.

“While we don’t know the exact clinical importance of the longer-term shedding of SARS-CoV-2 in individuals with COVID-19, some have speculated that those who have long-term shedding of SARS-CoV-2 may have ongoing infections that might benefit from treatment,” she said.

“Our data support the idea that the long-term GI-related symptoms in some people might be the consequence of an ongoing infection in the GI tract, even after the respiratory infection has cleared,” Dr. Bhatt said.

“Alternatively, the presence of ongoing viral genetic material in the gut might be a trigger for the immune system to continually be active against the virus, and our immune system reaction may be the reason for long COVID–type symptoms,” she added. “This area is ripe for additional studies.”

Dr. Bhatt and colleagues will continue studying viral shedding in fecal samples as part of the nationwide RECOVER Initiative.

When reached for comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview that previous studies have indicated that the virus may be detected in the stool for a month or more and for about 2 weeks on average. Whether the virus is infectious has been in question.

But it’s not so much that the virus is infectious in the GI tract and causing symptoms, he said. Rather, there are biomic changes related to COVID, including a loss of diversity in the gut bacteria, which disrupts the balance.

“This may actually in some way predispose some patients to impaired clearance of their symptoms,” Dr. Johnson explained. “There seems to be a growing recognition that this entity called long-haul COVID may be related to specific bacterial disruptions, and the more rapidly you can resolve these disruptions, the less likely you are to continue with long-haul symptoms.”

He said that, among people who have mild COVID, the virus typically clears and gut bacteria return to normal. With severe or persistent illness, gut dysbiosis persists, he said.

“People need to be aware that the GI tract is involved in a sizable percent of patients with COVID,” Dr. Johnson said. “The GI-tract testing may reflect that the virus is there, but persistence of the detectable test positivity is very unlikely to reflect active virus.”

The authors noted that they collected only six samples from the participants over the 10-month study period.

“Follow-up studies with more frequent sampling, especially in the first 2 months after diagnosis, may help build a more nuanced model of decline of fecal viral RNA concentration over time,” they wrote.

The study was supported by a Stanford ChemH-IMA grant, fellowships from the AACR and the National Science Foundation, and the National Institutes of Health. The authors and Dr. Johnson reported no relevant financial relationships. Dr. Johnson is a regular contributor to this news organization.

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

New data present further evidence that SARS-CoV-2 infection can settle in the gastrointestinal tract and that it can persist long after the infection has cleared the lungs.

Infection of the GI tract may figure prominently in long COVID, the study authors suggested.

Led by Aravind Natarajan, PhD, with the departments of genetics and medicine at Stanford (Calif.) University, they analyzed fecal RNA shedding up to 10 months after a COVID-19 diagnosis in 673 stool samples from 113 patients with mild to moderate disease.

They found that, in the week after diagnosis, COVID RNA remnants were present in the stool of approximately half (49.2%) of the patients. Seven months later, about 4% of them shed fecal viral RNA.

The authors noted that there was no ongoing SARS-CoV-2 RNA shedding in respiratory samples of patients at the 4-month mark.

Using self-reported symptoms regularly collected by questionnaire, they also found a correlation of long-term fecal shedding of SARS-CoV-2 RNA with abdominal pain, nausea, and vomiting.

The findings were published online in Med.
 

Implications of long-term viral shedding

Previous studies have found SARS-CoV-2 RNA in respiratory and fecal samples and have documented viral replication in lung and intestinal tissue. But before the current study, little had been known about long-term shedding, especially in those who have mild COVID. Most studies of viral shedding have been with severe COVID cases.

The authors noted that most studies of this kind are cross-sectional. The few other longitudinal studies have focused on early time points just after diagnosis.

Senior author Ami S. Bhatt, MD, associate professor in the departments of medicine and hematology at Stanford University, said in an interview that, though the viral genetic material in the feces lingers, on the basis of available evidence, it is highly unlikely to be contagious in most cases.

She said that understanding the dynamics of fecal shedding of SARS-CoV-2 genetic material will help interpret wastewater-based studies that are trying to determine population prevalence of the virus.

“While we don’t know the exact clinical importance of the longer-term shedding of SARS-CoV-2 in individuals with COVID-19, some have speculated that those who have long-term shedding of SARS-CoV-2 may have ongoing infections that might benefit from treatment,” she said.

“Our data support the idea that the long-term GI-related symptoms in some people might be the consequence of an ongoing infection in the GI tract, even after the respiratory infection has cleared,” Dr. Bhatt said.

“Alternatively, the presence of ongoing viral genetic material in the gut might be a trigger for the immune system to continually be active against the virus, and our immune system reaction may be the reason for long COVID–type symptoms,” she added. “This area is ripe for additional studies.”

Dr. Bhatt and colleagues will continue studying viral shedding in fecal samples as part of the nationwide RECOVER Initiative.

When reached for comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview that previous studies have indicated that the virus may be detected in the stool for a month or more and for about 2 weeks on average. Whether the virus is infectious has been in question.

But it’s not so much that the virus is infectious in the GI tract and causing symptoms, he said. Rather, there are biomic changes related to COVID, including a loss of diversity in the gut bacteria, which disrupts the balance.

“This may actually in some way predispose some patients to impaired clearance of their symptoms,” Dr. Johnson explained. “There seems to be a growing recognition that this entity called long-haul COVID may be related to specific bacterial disruptions, and the more rapidly you can resolve these disruptions, the less likely you are to continue with long-haul symptoms.”

He said that, among people who have mild COVID, the virus typically clears and gut bacteria return to normal. With severe or persistent illness, gut dysbiosis persists, he said.

“People need to be aware that the GI tract is involved in a sizable percent of patients with COVID,” Dr. Johnson said. “The GI-tract testing may reflect that the virus is there, but persistence of the detectable test positivity is very unlikely to reflect active virus.”

The authors noted that they collected only six samples from the participants over the 10-month study period.

“Follow-up studies with more frequent sampling, especially in the first 2 months after diagnosis, may help build a more nuanced model of decline of fecal viral RNA concentration over time,” they wrote.

The study was supported by a Stanford ChemH-IMA grant, fellowships from the AACR and the National Science Foundation, and the National Institutes of Health. The authors and Dr. Johnson reported no relevant financial relationships. Dr. Johnson is a regular contributor to this news organization.

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

Women with ductal carcinoma in situ (DCIS) breast cancer are generally uninformed about their diagnosis and are making uninformed treatment decisions, according to results of a study presented this month at ESMO Breast Cancer 2022, an annual meeting of the European Society for Medical Oncology.

The standard of care for women diagnosed with DCIS includes surgery with or without radiotherapy – even low-risk patients who are increasingly being steered toward active surveillance with annual mammograms. But few patients understand their diagnosis well enough to make informed decisions about treatment, according to a study led by Ellen Engelhardt, PhD, a postdoctoral fellow at The Netherlands Cancer Institute, Amsterdam.

“You’re not able to really have an informed preference until you understand the choices,” she said.

Dr. Engelhardt and colleagues surveyed 200 patients (mean age 59 years) from the LORD study, which is currently underway at The Netherlands Cancer Institute. The women were asked to complete a survey before treatment decisions were made. Their objective was to determine how knowledgeable patients were about DCIS. They found that only 34% of women answered four out of seven questions correctly: 19% of patients believed that DCIS could metastasize to organs other than the breast; 31% did not realize DCIS could progress to invasive breast cancer if left untreated; 79% thought DCIS could always be seen on mammograms; and, 93% said that progression could always be detected before it becomes “too extensive.” Knowledge of DCIS was found not to be associated with patient education level.

Susie X. Sun, MD, FACS, a breast surgeon at the University of Texas MD Anderson Cancer Center, Houston, said the findings clearly highlight a disconnect in communication between doctor and patient.

“I was surprised, because this clearly demonstrates there is a disconnect between what patients are being told by their providers and what is being perceived. It really shows us that we need to do a better job of making sure that our patients understand the information they’re given,” she said.

Dr. Sun, who was not involved in the study, said that DCIS needs to be explained well to patients. When they receive a diagnosis, often all they hear is, “I have breast cancer. It is really important for us to stress to patients how DCIS is different from invasive breast cancer,” she said.

The “Management of Low-risk (grade I and II) DCIS (LORD)” study is one of three studies comparing active surveillance to surgery (with or without radiotherapy).

A limitation of the study presented at ESMO Breast Cancer is that it remains unclear why patients answered questions incorrectly. Was information never communicated to them? Or, did they mishear or misunderstand the doctor? In future studies, Dr. Engelhardt and her colleagues plan to record and analyze audio tapes of consultations to determine where the communication disconnect lies.

Dr. Engelhardt did not disclose any conflicts associated with this work.

Women with ductal carcinoma in situ (DCIS) breast cancer are generally uninformed about their diagnosis and are making uninformed treatment decisions, according to results of a study presented this month at ESMO Breast Cancer 2022, an annual meeting of the European Society for Medical Oncology.

The standard of care for women diagnosed with DCIS includes surgery with or without radiotherapy – even low-risk patients who are increasingly being steered toward active surveillance with annual mammograms. But few patients understand their diagnosis well enough to make informed decisions about treatment, according to a study led by Ellen Engelhardt, PhD, a postdoctoral fellow at The Netherlands Cancer Institute, Amsterdam.

“You’re not able to really have an informed preference until you understand the choices,” she said.

Dr. Engelhardt and colleagues surveyed 200 patients (mean age 59 years) from the LORD study, which is currently underway at The Netherlands Cancer Institute. The women were asked to complete a survey before treatment decisions were made. Their objective was to determine how knowledgeable patients were about DCIS. They found that only 34% of women answered four out of seven questions correctly: 19% of patients believed that DCIS could metastasize to organs other than the breast; 31% did not realize DCIS could progress to invasive breast cancer if left untreated; 79% thought DCIS could always be seen on mammograms; and, 93% said that progression could always be detected before it becomes “too extensive.” Knowledge of DCIS was found not to be associated with patient education level.

Susie X. Sun, MD, FACS, a breast surgeon at the University of Texas MD Anderson Cancer Center, Houston, said the findings clearly highlight a disconnect in communication between doctor and patient.

“I was surprised, because this clearly demonstrates there is a disconnect between what patients are being told by their providers and what is being perceived. It really shows us that we need to do a better job of making sure that our patients understand the information they’re given,” she said.

Dr. Sun, who was not involved in the study, said that DCIS needs to be explained well to patients. When they receive a diagnosis, often all they hear is, “I have breast cancer. It is really important for us to stress to patients how DCIS is different from invasive breast cancer,” she said.

The “Management of Low-risk (grade I and II) DCIS (LORD)” study is one of three studies comparing active surveillance to surgery (with or without radiotherapy).

A limitation of the study presented at ESMO Breast Cancer is that it remains unclear why patients answered questions incorrectly. Was information never communicated to them? Or, did they mishear or misunderstand the doctor? In future studies, Dr. Engelhardt and her colleagues plan to record and analyze audio tapes of consultations to determine where the communication disconnect lies.

Dr. Engelhardt did not disclose any conflicts associated with this work.

Women with ductal carcinoma in situ (DCIS) breast cancer are generally uninformed about their diagnosis and are making uninformed treatment decisions, according to results of a study presented this month at ESMO Breast Cancer 2022, an annual meeting of the European Society for Medical Oncology.

The standard of care for women diagnosed with DCIS includes surgery with or without radiotherapy – even low-risk patients who are increasingly being steered toward active surveillance with annual mammograms. But few patients understand their diagnosis well enough to make informed decisions about treatment, according to a study led by Ellen Engelhardt, PhD, a postdoctoral fellow at The Netherlands Cancer Institute, Amsterdam.

“You’re not able to really have an informed preference until you understand the choices,” she said.

Dr. Engelhardt and colleagues surveyed 200 patients (mean age 59 years) from the LORD study, which is currently underway at The Netherlands Cancer Institute. The women were asked to complete a survey before treatment decisions were made. Their objective was to determine how knowledgeable patients were about DCIS. They found that only 34% of women answered four out of seven questions correctly: 19% of patients believed that DCIS could metastasize to organs other than the breast; 31% did not realize DCIS could progress to invasive breast cancer if left untreated; 79% thought DCIS could always be seen on mammograms; and, 93% said that progression could always be detected before it becomes “too extensive.” Knowledge of DCIS was found not to be associated with patient education level.

Susie X. Sun, MD, FACS, a breast surgeon at the University of Texas MD Anderson Cancer Center, Houston, said the findings clearly highlight a disconnect in communication between doctor and patient.

“I was surprised, because this clearly demonstrates there is a disconnect between what patients are being told by their providers and what is being perceived. It really shows us that we need to do a better job of making sure that our patients understand the information they’re given,” she said.

Dr. Sun, who was not involved in the study, said that DCIS needs to be explained well to patients. When they receive a diagnosis, often all they hear is, “I have breast cancer. It is really important for us to stress to patients how DCIS is different from invasive breast cancer,” she said.

The “Management of Low-risk (grade I and II) DCIS (LORD)” study is one of three studies comparing active surveillance to surgery (with or without radiotherapy).

A limitation of the study presented at ESMO Breast Cancer is that it remains unclear why patients answered questions incorrectly. Was information never communicated to them? Or, did they mishear or misunderstand the doctor? In future studies, Dr. Engelhardt and her colleagues plan to record and analyze audio tapes of consultations to determine where the communication disconnect lies.

Dr. Engelhardt did not disclose any conflicts associated with this work.

New data present further evidence that SARS-CoV-2 infection can settle in the gastrointestinal (GI) tract and that it can persist long after the infection has cleared the lungs.

Infection of the GI tract may figure prominently in long COVID, the study authors suggest.

Led by Aravind Natarajan, PhD, with the departments of genetics and medicine at Stanford (Calif.) University, they analyzed fecal RNA shedding up to 10 months after a COVID-19 diagnosis in 673 stool samples from 113 patients with mild to moderate disease.

They found that in the week after diagnosis, COVID RNA remnants were present in the stool of approximately half (49.2%) of the patients. Seven months later, about 4% of them shed fecal viral RNA.

The authors note that there was no ongoing SARS-CoV-2 RNA shedding in respiratory samples of patients at the 4-month mark.

Using self-reported symptoms regularly collected by questionnaire, they also found a correlation of long-term fecal shedding of SARS-CoV-2 RNA with abdominal pain, nausea, and vomiting.

The findings were published online in Med.
 

Implications of long-term viral shedding

Previous studies have found SARS-CoV-2 RNA in respiratory and fecal samples and have documented viral replication in lung and intestinal tissue.

But before the current study, little had been known about long-term shedding, especially in those who have mild COVID. Most studies of viral shedding have been with severe COVID cases.

The authors note that most studies of this kind are cross-sectional. The few other longitudinal studies have focused on early time points just after diagnosis.

Senior author Ami S. Bhatt, MD, associate professor in the departments of medicine and hematology at Stanford, told this news organization that though the viral genetic material in the feces lingers, on the basis of available evidence, it is highly unlikely to be contagious in most cases.

She said that understanding the dynamics of fecal shedding of SARS-CoV-2 genetic material will help interpret wastewater-based studies that are trying to determine population prevalence of the virus.

“While we don’t know the exact clinical importance of the longer-term shedding of SARS-CoV-2 in individuals with COVID-19, some have speculated that those who have long-term shedding of SARS-CoV-2 may have ongoing infections that might benefit from treatment,” she said.

“Our data support the idea that the long-term GI-related symptoms in some people might be the consequence of an ongoing infection in the GI tract, even after the respiratory infection has cleared,” Dr. Bhatt said.

“Alternatively, the presence of ongoing viral genetic material in the gut might be a trigger for the immune system to continually be active against the virus, and our immune system reaction may be the reason for long-COVID type symptoms,” she added. “This area is ripe for additional studies.”

Dr. Bhatt and colleagues will continue studying viral shedding in fecal samples as part of the nationwide RECOVER Initiative.

When reached for comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview that previous studies have indicated that the virus may be detected in the stool for a month or more and for about 2 weeks on average. Whether the virus is infectious has been in question.

But it’s not so much that the virus is infectious in the GI tract and causing symptoms, he said. Rather, there are biomic changes related to COVID, including a loss of diversity in the gut bacteria, which disrupts the balance.

“This may actually in some way predispose some patients to impaired clearance of their symptoms,” Dr. Johnson explained. “There seems to be a growing recognition that this entity called long-haul COVID may be related to specific bacterial disruptions, and the more rapidly you can resolve these disruptions, the less likely you are to continue with long-haul symptoms.”

He said that among people who have mild COVID, the virus typically clears and gut bacteria return to normal. With severe or persistent illness, gut dysbiosis persists, he said.

“People need to be aware that the GI tract is involved in a sizable percent of patients with COVID,” Dr. Johnson said. “The GI-tract testing may reflect that the virus is there, but persistence of the detectable test positivity is very unlikely to reflect active virus.”

The authors note in this study that they collected only six samples from the participants over the 10-month period.

“Follow-up studies with more frequent sampling, especially in the first 2 months after diagnosis, may help build a more nuanced model of decline of fecal viral RNA concentration over time,” they write.

The study was supported by a Stanford ChemH-IMA grant, fellowships from the AACR and the National Science Foundation, and the National Institutes of Health. The authors and Dr. Johnson report no relevant financial relationships. Dr. Johnson is a regular contributor to Medscape.

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

New data present further evidence that SARS-CoV-2 infection can settle in the gastrointestinal (GI) tract and that it can persist long after the infection has cleared the lungs.

Infection of the GI tract may figure prominently in long COVID, the study authors suggest.

Led by Aravind Natarajan, PhD, with the departments of genetics and medicine at Stanford (Calif.) University, they analyzed fecal RNA shedding up to 10 months after a COVID-19 diagnosis in 673 stool samples from 113 patients with mild to moderate disease.

They found that in the week after diagnosis, COVID RNA remnants were present in the stool of approximately half (49.2%) of the patients. Seven months later, about 4% of them shed fecal viral RNA.

The authors note that there was no ongoing SARS-CoV-2 RNA shedding in respiratory samples of patients at the 4-month mark.

Using self-reported symptoms regularly collected by questionnaire, they also found a correlation of long-term fecal shedding of SARS-CoV-2 RNA with abdominal pain, nausea, and vomiting.

The findings were published online in Med.
 

Implications of long-term viral shedding

Previous studies have found SARS-CoV-2 RNA in respiratory and fecal samples and have documented viral replication in lung and intestinal tissue.

But before the current study, little had been known about long-term shedding, especially in those who have mild COVID. Most studies of viral shedding have been with severe COVID cases.

The authors note that most studies of this kind are cross-sectional. The few other longitudinal studies have focused on early time points just after diagnosis.

Senior author Ami S. Bhatt, MD, associate professor in the departments of medicine and hematology at Stanford, told this news organization that though the viral genetic material in the feces lingers, on the basis of available evidence, it is highly unlikely to be contagious in most cases.

She said that understanding the dynamics of fecal shedding of SARS-CoV-2 genetic material will help interpret wastewater-based studies that are trying to determine population prevalence of the virus.

“While we don’t know the exact clinical importance of the longer-term shedding of SARS-CoV-2 in individuals with COVID-19, some have speculated that those who have long-term shedding of SARS-CoV-2 may have ongoing infections that might benefit from treatment,” she said.

“Our data support the idea that the long-term GI-related symptoms in some people might be the consequence of an ongoing infection in the GI tract, even after the respiratory infection has cleared,” Dr. Bhatt said.

“Alternatively, the presence of ongoing viral genetic material in the gut might be a trigger for the immune system to continually be active against the virus, and our immune system reaction may be the reason for long-COVID type symptoms,” she added. “This area is ripe for additional studies.”

Dr. Bhatt and colleagues will continue studying viral shedding in fecal samples as part of the nationwide RECOVER Initiative.

When reached for comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview that previous studies have indicated that the virus may be detected in the stool for a month or more and for about 2 weeks on average. Whether the virus is infectious has been in question.

But it’s not so much that the virus is infectious in the GI tract and causing symptoms, he said. Rather, there are biomic changes related to COVID, including a loss of diversity in the gut bacteria, which disrupts the balance.

“This may actually in some way predispose some patients to impaired clearance of their symptoms,” Dr. Johnson explained. “There seems to be a growing recognition that this entity called long-haul COVID may be related to specific bacterial disruptions, and the more rapidly you can resolve these disruptions, the less likely you are to continue with long-haul symptoms.”

He said that among people who have mild COVID, the virus typically clears and gut bacteria return to normal. With severe or persistent illness, gut dysbiosis persists, he said.

“People need to be aware that the GI tract is involved in a sizable percent of patients with COVID,” Dr. Johnson said. “The GI-tract testing may reflect that the virus is there, but persistence of the detectable test positivity is very unlikely to reflect active virus.”

The authors note in this study that they collected only six samples from the participants over the 10-month period.

“Follow-up studies with more frequent sampling, especially in the first 2 months after diagnosis, may help build a more nuanced model of decline of fecal viral RNA concentration over time,” they write.

The study was supported by a Stanford ChemH-IMA grant, fellowships from the AACR and the National Science Foundation, and the National Institutes of Health. The authors and Dr. Johnson report no relevant financial relationships. Dr. Johnson is a regular contributor to Medscape.

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

New data present further evidence that SARS-CoV-2 infection can settle in the gastrointestinal (GI) tract and that it can persist long after the infection has cleared the lungs.

Infection of the GI tract may figure prominently in long COVID, the study authors suggest.

Led by Aravind Natarajan, PhD, with the departments of genetics and medicine at Stanford (Calif.) University, they analyzed fecal RNA shedding up to 10 months after a COVID-19 diagnosis in 673 stool samples from 113 patients with mild to moderate disease.

They found that in the week after diagnosis, COVID RNA remnants were present in the stool of approximately half (49.2%) of the patients. Seven months later, about 4% of them shed fecal viral RNA.

The authors note that there was no ongoing SARS-CoV-2 RNA shedding in respiratory samples of patients at the 4-month mark.

Using self-reported symptoms regularly collected by questionnaire, they also found a correlation of long-term fecal shedding of SARS-CoV-2 RNA with abdominal pain, nausea, and vomiting.

The findings were published online in Med.
 

Implications of long-term viral shedding

Previous studies have found SARS-CoV-2 RNA in respiratory and fecal samples and have documented viral replication in lung and intestinal tissue.

But before the current study, little had been known about long-term shedding, especially in those who have mild COVID. Most studies of viral shedding have been with severe COVID cases.

The authors note that most studies of this kind are cross-sectional. The few other longitudinal studies have focused on early time points just after diagnosis.

Senior author Ami S. Bhatt, MD, associate professor in the departments of medicine and hematology at Stanford, told this news organization that though the viral genetic material in the feces lingers, on the basis of available evidence, it is highly unlikely to be contagious in most cases.

She said that understanding the dynamics of fecal shedding of SARS-CoV-2 genetic material will help interpret wastewater-based studies that are trying to determine population prevalence of the virus.

“While we don’t know the exact clinical importance of the longer-term shedding of SARS-CoV-2 in individuals with COVID-19, some have speculated that those who have long-term shedding of SARS-CoV-2 may have ongoing infections that might benefit from treatment,” she said.

“Our data support the idea that the long-term GI-related symptoms in some people might be the consequence of an ongoing infection in the GI tract, even after the respiratory infection has cleared,” Dr. Bhatt said.

“Alternatively, the presence of ongoing viral genetic material in the gut might be a trigger for the immune system to continually be active against the virus, and our immune system reaction may be the reason for long-COVID type symptoms,” she added. “This area is ripe for additional studies.”

Dr. Bhatt and colleagues will continue studying viral shedding in fecal samples as part of the nationwide RECOVER Initiative.

When reached for comment, David A. Johnson, MD, professor of medicine and chief of gastroenterology, Eastern Virginia Medical School, Norfolk, said in an interview that previous studies have indicated that the virus may be detected in the stool for a month or more and for about 2 weeks on average. Whether the virus is infectious has been in question.

But it’s not so much that the virus is infectious in the GI tract and causing symptoms, he said. Rather, there are biomic changes related to COVID, including a loss of diversity in the gut bacteria, which disrupts the balance.

“This may actually in some way predispose some patients to impaired clearance of their symptoms,” Dr. Johnson explained. “There seems to be a growing recognition that this entity called long-haul COVID may be related to specific bacterial disruptions, and the more rapidly you can resolve these disruptions, the less likely you are to continue with long-haul symptoms.”

He said that among people who have mild COVID, the virus typically clears and gut bacteria return to normal. With severe or persistent illness, gut dysbiosis persists, he said.

“People need to be aware that the GI tract is involved in a sizable percent of patients with COVID,” Dr. Johnson said. “The GI-tract testing may reflect that the virus is there, but persistence of the detectable test positivity is very unlikely to reflect active virus.”

The authors note in this study that they collected only six samples from the participants over the 10-month period.

“Follow-up studies with more frequent sampling, especially in the first 2 months after diagnosis, may help build a more nuanced model of decline of fecal viral RNA concentration over time,” they write.

The study was supported by a Stanford ChemH-IMA grant, fellowships from the AACR and the National Science Foundation, and the National Institutes of Health. The authors and Dr. Johnson report no relevant financial relationships. Dr. Johnson is a regular contributor to Medscape.

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