Mixed Topics

Eight Navy sailors have died by suicide in less than a year. The most recent death was on January 23. Three sailors who died in the past 2 months have more than suicide in common: They were all stationed aboard Navy aircraft carriers undergoing refits: the USS George Washington and the USS Theodore Roosevelt. 

These deaths come only a month after the Navy released a report on 3 deaths by suicide on the George Washington, all of which happened in a single week last April. Military.com reported that the ship’s commander, Capt. Brent Gaut, had said 10 sailors had died by suicide in under a year. 

In November and December 2022, at least 4 sailors assigned to the Mid-Atlantic Regional Maintenance Center (MARMC) in Virginia died by suicide, multiplying concerns about a fleetwide mental health crisis. “I was inundated with the amount of hopelessness at that command,” Kayla Arestivo, a counselor brought in to help, told nbcnews.com. Sailors spoke of being overworked, undervalued, and not getting the mental health help they needed. “Part of it is toxic leadership. The sailors immediately pointed that out,” Arestivo said. 

She noted that many of the people assigned to MARMC are on limited duty due to mental or physical disabilities or have personal stressors that prevent them from full unrestricted duty. Electronics technician Kody Lee Decker, for instance, was on limited duty due to mental health issues when he died by suicide on October 29, 2022, according to a friend. Those people, Arestivo suggested, should have been provided help earlier.

Disabilities are not the only potential risk factors, though. Sailors living aboard the George Washington from April 2021 until April 2022 reported difficult and noisy living conditions with shortages of power, running water, and heat, and poor ventilation. Sailors would sleep in their cars or rent rooms in town rather than stay on board. 

The George Washington has been docked at Newport News [Virginia] Shipbuilding for a major overhaul and repairs since 2017 (expected to extend into 2023, nearly 2 years later than the original deadline). The Navy investigation acknowledged “overwhelming” stress and noted that the living conditions created by an “intense and complex” maintenance process were posing hardships for the sailors, including sleep deprivation. (The Theodore Roosevelt has been at the Puget Sound shipyard since August 2021, although none of the sailors live onboard.)

However, the Navy investigation concluded that the 3 April suicide deaths were not directly connected to living conditions. According to the US Fleet Forces Command, “each Sailor was experiencing unique and individualized life stressors, which were contributing factors leading to their deaths.” The 3 suicide deaths were deemed independent events, with no direct correlation among them.

But the report also charged that leaders were oblivious to the problems, and the mental health care the Navy offered was insufficient: “Multiple command members knew or should have known that MASR Mitchell-Sandor [who died by suicide] was experiencing displeasure with Navy life and could have intervened to help him better cope or seek out available support services.”

In the official response to the Navy report, Rear Adm. John Meier, Commander, Naval Air Force Atlantic, noted that he had convened a “second and broader investigation” to assess quality of life issues and other systemic issues for aircraft carriers undergoing extensive maintenance or construction in the Newport News shipyard. “It is safe to say,” he wrote, that “generations of Navy leaders had become accustomed to the reduced quality of life in the shipyard, and accepted the status quo as par for the course…” 

He agreed that the general stress of the environment was not the root cause of the deaths but was “certainly a contributing factor” in at least one case. The report, he said, placed too much emphasis on the sailor’s personal decisions to not improve his own living conditions (he was offered the opportunity to change berthing) and thus placed “too much burden on him for his situation.” Senior enlisted leadership knew that the sailor was sleeping in his car and counseled him, but Meier found no evidence of follow-through. More senior sailors or an assigned mentor should have been there to support the sailor, Meier said, and help him make decisions that were in his best interests. “This was a time for intrusive leadership.”

Adm. Daryl Caudle, Commander, US Fleet Forces Command, advised revising the wording in the report to say “No one at the command knew, or had a reason to know, of MASR [Xavier] Mitchell-Sandor’s previous suicidal ideations.” He also advised modifying the wording with: “Had the Navy been aware of MASR Mitchell-Sandor’s previous suicidal ideations, existing programs and procedures were in place that make it likely that he would have been placed in a ‘do not arm’ status and received necessary care.”

Vice Admiral Kenneth Whitesell, Commander, Naval Air Force, US Pacific Fleet, also endorsed the report findings with some revisions, saying, “We cannot assume these issues are isolated to a single ship, or to shipyards alone. Rather, these 3 tragic losses brought to light the ultimate need to remain laser-focused on providing care and guidance to our sailors.”

The Navy is providing mental health support to sailors, including an embedded mental health team and 2 civilian resiliency counselors who work on the George Washington. According to an action update in the report, Commander, Naval Air Force directed all CVNs and Naval Aviation Units to have a minimum of 1 safeTALK (Suicide Alertness For Everyone; Tell, Ask, Listen and KeepSafe) trained member onboard, and 2 to 3 safeTALK trained personnel in each division no later than December 31, 2022. 

At MARMC, Arestivo was brought in for several mandatory suicide prevention sessions but without systemic changes, she said, “We’re putting Band-Aids on bullet holes.”

She said she told MARMC’s commanding officer, “You will have another one.” The fourth sailor died by suicide 10 days later.

If you or someone you know is having thoughts of suicide, call or text 988 to reach the National Suicide Prevention Lifeline or contact the Veterans Crisis Line. 

Eight Navy sailors have died by suicide in less than a year. The most recent death was on January 23. Three sailors who died in the past 2 months have more than suicide in common: They were all stationed aboard Navy aircraft carriers undergoing refits: the USS George Washington and the USS Theodore Roosevelt. 

These deaths come only a month after the Navy released a report on 3 deaths by suicide on the George Washington, all of which happened in a single week last April. Military.com reported that the ship’s commander, Capt. Brent Gaut, had said 10 sailors had died by suicide in under a year. 

In November and December 2022, at least 4 sailors assigned to the Mid-Atlantic Regional Maintenance Center (MARMC) in Virginia died by suicide, multiplying concerns about a fleetwide mental health crisis. “I was inundated with the amount of hopelessness at that command,” Kayla Arestivo, a counselor brought in to help, told nbcnews.com. Sailors spoke of being overworked, undervalued, and not getting the mental health help they needed. “Part of it is toxic leadership. The sailors immediately pointed that out,” Arestivo said. 

She noted that many of the people assigned to MARMC are on limited duty due to mental or physical disabilities or have personal stressors that prevent them from full unrestricted duty. Electronics technician Kody Lee Decker, for instance, was on limited duty due to mental health issues when he died by suicide on October 29, 2022, according to a friend. Those people, Arestivo suggested, should have been provided help earlier.

Disabilities are not the only potential risk factors, though. Sailors living aboard the George Washington from April 2021 until April 2022 reported difficult and noisy living conditions with shortages of power, running water, and heat, and poor ventilation. Sailors would sleep in their cars or rent rooms in town rather than stay on board. 

The George Washington has been docked at Newport News [Virginia] Shipbuilding for a major overhaul and repairs since 2017 (expected to extend into 2023, nearly 2 years later than the original deadline). The Navy investigation acknowledged “overwhelming” stress and noted that the living conditions created by an “intense and complex” maintenance process were posing hardships for the sailors, including sleep deprivation. (The Theodore Roosevelt has been at the Puget Sound shipyard since August 2021, although none of the sailors live onboard.)

However, the Navy investigation concluded that the 3 April suicide deaths were not directly connected to living conditions. According to the US Fleet Forces Command, “each Sailor was experiencing unique and individualized life stressors, which were contributing factors leading to their deaths.” The 3 suicide deaths were deemed independent events, with no direct correlation among them.

But the report also charged that leaders were oblivious to the problems, and the mental health care the Navy offered was insufficient: “Multiple command members knew or should have known that MASR Mitchell-Sandor [who died by suicide] was experiencing displeasure with Navy life and could have intervened to help him better cope or seek out available support services.”

In the official response to the Navy report, Rear Adm. John Meier, Commander, Naval Air Force Atlantic, noted that he had convened a “second and broader investigation” to assess quality of life issues and other systemic issues for aircraft carriers undergoing extensive maintenance or construction in the Newport News shipyard. “It is safe to say,” he wrote, that “generations of Navy leaders had become accustomed to the reduced quality of life in the shipyard, and accepted the status quo as par for the course…” 

He agreed that the general stress of the environment was not the root cause of the deaths but was “certainly a contributing factor” in at least one case. The report, he said, placed too much emphasis on the sailor’s personal decisions to not improve his own living conditions (he was offered the opportunity to change berthing) and thus placed “too much burden on him for his situation.” Senior enlisted leadership knew that the sailor was sleeping in his car and counseled him, but Meier found no evidence of follow-through. More senior sailors or an assigned mentor should have been there to support the sailor, Meier said, and help him make decisions that were in his best interests. “This was a time for intrusive leadership.”

Adm. Daryl Caudle, Commander, US Fleet Forces Command, advised revising the wording in the report to say “No one at the command knew, or had a reason to know, of MASR [Xavier] Mitchell-Sandor’s previous suicidal ideations.” He also advised modifying the wording with: “Had the Navy been aware of MASR Mitchell-Sandor’s previous suicidal ideations, existing programs and procedures were in place that make it likely that he would have been placed in a ‘do not arm’ status and received necessary care.”

Vice Admiral Kenneth Whitesell, Commander, Naval Air Force, US Pacific Fleet, also endorsed the report findings with some revisions, saying, “We cannot assume these issues are isolated to a single ship, or to shipyards alone. Rather, these 3 tragic losses brought to light the ultimate need to remain laser-focused on providing care and guidance to our sailors.”

The Navy is providing mental health support to sailors, including an embedded mental health team and 2 civilian resiliency counselors who work on the George Washington. According to an action update in the report, Commander, Naval Air Force directed all CVNs and Naval Aviation Units to have a minimum of 1 safeTALK (Suicide Alertness For Everyone; Tell, Ask, Listen and KeepSafe) trained member onboard, and 2 to 3 safeTALK trained personnel in each division no later than December 31, 2022. 

At MARMC, Arestivo was brought in for several mandatory suicide prevention sessions but without systemic changes, she said, “We’re putting Band-Aids on bullet holes.”

She said she told MARMC’s commanding officer, “You will have another one.” The fourth sailor died by suicide 10 days later.

If you or someone you know is having thoughts of suicide, call or text 988 to reach the National Suicide Prevention Lifeline or contact the Veterans Crisis Line. 

Eight Navy sailors have died by suicide in less than a year. The most recent death was on January 23. Three sailors who died in the past 2 months have more than suicide in common: They were all stationed aboard Navy aircraft carriers undergoing refits: the USS George Washington and the USS Theodore Roosevelt. 

These deaths come only a month after the Navy released a report on 3 deaths by suicide on the George Washington, all of which happened in a single week last April. Military.com reported that the ship’s commander, Capt. Brent Gaut, had said 10 sailors had died by suicide in under a year. 

In November and December 2022, at least 4 sailors assigned to the Mid-Atlantic Regional Maintenance Center (MARMC) in Virginia died by suicide, multiplying concerns about a fleetwide mental health crisis. “I was inundated with the amount of hopelessness at that command,” Kayla Arestivo, a counselor brought in to help, told nbcnews.com. Sailors spoke of being overworked, undervalued, and not getting the mental health help they needed. “Part of it is toxic leadership. The sailors immediately pointed that out,” Arestivo said. 

She noted that many of the people assigned to MARMC are on limited duty due to mental or physical disabilities or have personal stressors that prevent them from full unrestricted duty. Electronics technician Kody Lee Decker, for instance, was on limited duty due to mental health issues when he died by suicide on October 29, 2022, according to a friend. Those people, Arestivo suggested, should have been provided help earlier.

Disabilities are not the only potential risk factors, though. Sailors living aboard the George Washington from April 2021 until April 2022 reported difficult and noisy living conditions with shortages of power, running water, and heat, and poor ventilation. Sailors would sleep in their cars or rent rooms in town rather than stay on board. 

The George Washington has been docked at Newport News [Virginia] Shipbuilding for a major overhaul and repairs since 2017 (expected to extend into 2023, nearly 2 years later than the original deadline). The Navy investigation acknowledged “overwhelming” stress and noted that the living conditions created by an “intense and complex” maintenance process were posing hardships for the sailors, including sleep deprivation. (The Theodore Roosevelt has been at the Puget Sound shipyard since August 2021, although none of the sailors live onboard.)

However, the Navy investigation concluded that the 3 April suicide deaths were not directly connected to living conditions. According to the US Fleet Forces Command, “each Sailor was experiencing unique and individualized life stressors, which were contributing factors leading to their deaths.” The 3 suicide deaths were deemed independent events, with no direct correlation among them.

But the report also charged that leaders were oblivious to the problems, and the mental health care the Navy offered was insufficient: “Multiple command members knew or should have known that MASR Mitchell-Sandor [who died by suicide] was experiencing displeasure with Navy life and could have intervened to help him better cope or seek out available support services.”

In the official response to the Navy report, Rear Adm. John Meier, Commander, Naval Air Force Atlantic, noted that he had convened a “second and broader investigation” to assess quality of life issues and other systemic issues for aircraft carriers undergoing extensive maintenance or construction in the Newport News shipyard. “It is safe to say,” he wrote, that “generations of Navy leaders had become accustomed to the reduced quality of life in the shipyard, and accepted the status quo as par for the course…” 

He agreed that the general stress of the environment was not the root cause of the deaths but was “certainly a contributing factor” in at least one case. The report, he said, placed too much emphasis on the sailor’s personal decisions to not improve his own living conditions (he was offered the opportunity to change berthing) and thus placed “too much burden on him for his situation.” Senior enlisted leadership knew that the sailor was sleeping in his car and counseled him, but Meier found no evidence of follow-through. More senior sailors or an assigned mentor should have been there to support the sailor, Meier said, and help him make decisions that were in his best interests. “This was a time for intrusive leadership.”

Adm. Daryl Caudle, Commander, US Fleet Forces Command, advised revising the wording in the report to say “No one at the command knew, or had a reason to know, of MASR [Xavier] Mitchell-Sandor’s previous suicidal ideations.” He also advised modifying the wording with: “Had the Navy been aware of MASR Mitchell-Sandor’s previous suicidal ideations, existing programs and procedures were in place that make it likely that he would have been placed in a ‘do not arm’ status and received necessary care.”

Vice Admiral Kenneth Whitesell, Commander, Naval Air Force, US Pacific Fleet, also endorsed the report findings with some revisions, saying, “We cannot assume these issues are isolated to a single ship, or to shipyards alone. Rather, these 3 tragic losses brought to light the ultimate need to remain laser-focused on providing care and guidance to our sailors.”

The Navy is providing mental health support to sailors, including an embedded mental health team and 2 civilian resiliency counselors who work on the George Washington. According to an action update in the report, Commander, Naval Air Force directed all CVNs and Naval Aviation Units to have a minimum of 1 safeTALK (Suicide Alertness For Everyone; Tell, Ask, Listen and KeepSafe) trained member onboard, and 2 to 3 safeTALK trained personnel in each division no later than December 31, 2022. 

At MARMC, Arestivo was brought in for several mandatory suicide prevention sessions but without systemic changes, she said, “We’re putting Band-Aids on bullet holes.”

She said she told MARMC’s commanding officer, “You will have another one.” The fourth sailor died by suicide 10 days later.

If you or someone you know is having thoughts of suicide, call or text 988 to reach the National Suicide Prevention Lifeline or contact the Veterans Crisis Line. 

Cases of nonventilator-associated hospital-acquired pneumonia (NV-HAP) declined by 32% between 2015 and 2020. Then, of course, COVID-19 changed the trajectory and rates began to rise. After February 2020, the incidence rate rose by 25% among veterans without COVID-19—but by 108% among those who had COVID-19. 

Those are findings from a study by researchers at Rocky Mountain Regional VA Medical Center, Aurora, Colorado. They studied data on 1,567,275 veterans admitted to 135 VA facilities in acute care settings between October 2015 and March 2021, with a stay of at least 48 hours.

They say, to their knowledge, this is the first published report of changes in NV-HAP risk associated with the onset of COVID-19 among all hospitalized veterans in a national health care system.

The questions for the researchers were: What drove the increase in NV-HAP rates? Was it the elevated risk among veterans with COVID-19, reduced NV-HAP prevention measures during the extreme pandemic-related stress on the system, and/or increased patient acuity among hospitalized veterans? 

They concluded that the observed increase in NV-HAP risk among all patients during the COVID-19 pandemic is “likely multifactorial.” The stresses on clinical workload may have hampered fundamental preventive nursing care, such as early mobility programs, consistent oral care, and aspiration precautions. The researchers also cite barriers including wearing personal protective equipment, which affected communication and the ability to get needed supplies to the bedside without cross-contamination.

Among patients with COVID-19 infections, the greater NV-HAP risk could be due to changes in the lower respiratory tract microbiome, disruption of the immune response, and synergism seen with COVID-19 infection. Moreover, they note, placing patients in a prone position to improve oxygenation might have raised the risk of NV-HAP.

The hospitalized veterans in the study also had a high burden of clinical comorbidities. Those with COVID-19 were more likely to have documented diagnosis of dementia in the previous year, compared with COVID-19-negative veterans or those hospitalized before the pandemic began. The researchers point out that dementia increased the risk of microaspiration, which can lead to secondary bacterial pneumonia.

In addition to reinforcing prevention efforts, the researchers suggest that NV-HAP monitoring via automated electronic surveillance could “serve as a cornerstone of a strong infection prevention program.” A system like that, installed before the pandemic, they say, might have identified the NV-HAP risk sooner. 

Most importantly, they add, strategies to reduce NV-HAP risk “should be designed with resilience to significant system stress such as the COVID-19 pandemic.” 

Cases of nonventilator-associated hospital-acquired pneumonia (NV-HAP) declined by 32% between 2015 and 2020. Then, of course, COVID-19 changed the trajectory and rates began to rise. After February 2020, the incidence rate rose by 25% among veterans without COVID-19—but by 108% among those who had COVID-19. 

Those are findings from a study by researchers at Rocky Mountain Regional VA Medical Center, Aurora, Colorado. They studied data on 1,567,275 veterans admitted to 135 VA facilities in acute care settings between October 2015 and March 2021, with a stay of at least 48 hours.

They say, to their knowledge, this is the first published report of changes in NV-HAP risk associated with the onset of COVID-19 among all hospitalized veterans in a national health care system.

The questions for the researchers were: What drove the increase in NV-HAP rates? Was it the elevated risk among veterans with COVID-19, reduced NV-HAP prevention measures during the extreme pandemic-related stress on the system, and/or increased patient acuity among hospitalized veterans? 

They concluded that the observed increase in NV-HAP risk among all patients during the COVID-19 pandemic is “likely multifactorial.” The stresses on clinical workload may have hampered fundamental preventive nursing care, such as early mobility programs, consistent oral care, and aspiration precautions. The researchers also cite barriers including wearing personal protective equipment, which affected communication and the ability to get needed supplies to the bedside without cross-contamination.

Among patients with COVID-19 infections, the greater NV-HAP risk could be due to changes in the lower respiratory tract microbiome, disruption of the immune response, and synergism seen with COVID-19 infection. Moreover, they note, placing patients in a prone position to improve oxygenation might have raised the risk of NV-HAP.

The hospitalized veterans in the study also had a high burden of clinical comorbidities. Those with COVID-19 were more likely to have documented diagnosis of dementia in the previous year, compared with COVID-19-negative veterans or those hospitalized before the pandemic began. The researchers point out that dementia increased the risk of microaspiration, which can lead to secondary bacterial pneumonia.

In addition to reinforcing prevention efforts, the researchers suggest that NV-HAP monitoring via automated electronic surveillance could “serve as a cornerstone of a strong infection prevention program.” A system like that, installed before the pandemic, they say, might have identified the NV-HAP risk sooner. 

Most importantly, they add, strategies to reduce NV-HAP risk “should be designed with resilience to significant system stress such as the COVID-19 pandemic.” 

Cases of nonventilator-associated hospital-acquired pneumonia (NV-HAP) declined by 32% between 2015 and 2020. Then, of course, COVID-19 changed the trajectory and rates began to rise. After February 2020, the incidence rate rose by 25% among veterans without COVID-19—but by 108% among those who had COVID-19. 

Those are findings from a study by researchers at Rocky Mountain Regional VA Medical Center, Aurora, Colorado. They studied data on 1,567,275 veterans admitted to 135 VA facilities in acute care settings between October 2015 and March 2021, with a stay of at least 48 hours.

They say, to their knowledge, this is the first published report of changes in NV-HAP risk associated with the onset of COVID-19 among all hospitalized veterans in a national health care system.

The questions for the researchers were: What drove the increase in NV-HAP rates? Was it the elevated risk among veterans with COVID-19, reduced NV-HAP prevention measures during the extreme pandemic-related stress on the system, and/or increased patient acuity among hospitalized veterans? 

They concluded that the observed increase in NV-HAP risk among all patients during the COVID-19 pandemic is “likely multifactorial.” The stresses on clinical workload may have hampered fundamental preventive nursing care, such as early mobility programs, consistent oral care, and aspiration precautions. The researchers also cite barriers including wearing personal protective equipment, which affected communication and the ability to get needed supplies to the bedside without cross-contamination.

Among patients with COVID-19 infections, the greater NV-HAP risk could be due to changes in the lower respiratory tract microbiome, disruption of the immune response, and synergism seen with COVID-19 infection. Moreover, they note, placing patients in a prone position to improve oxygenation might have raised the risk of NV-HAP.

The hospitalized veterans in the study also had a high burden of clinical comorbidities. Those with COVID-19 were more likely to have documented diagnosis of dementia in the previous year, compared with COVID-19-negative veterans or those hospitalized before the pandemic began. The researchers point out that dementia increased the risk of microaspiration, which can lead to secondary bacterial pneumonia.

In addition to reinforcing prevention efforts, the researchers suggest that NV-HAP monitoring via automated electronic surveillance could “serve as a cornerstone of a strong infection prevention program.” A system like that, installed before the pandemic, they say, might have identified the NV-HAP risk sooner. 

Most importantly, they add, strategies to reduce NV-HAP risk “should be designed with resilience to significant system stress such as the COVID-19 pandemic.” 

Is the ketogenic diet the only way to lose weight? Of course not! Keep track of calories in vs. calories out and almost anyone can lose weight. The problem is keeping it off. To understand that, we need to look at metabolic adaptation and the biology of obesity.

Our bodies have a “set point” that is epigenetically latched onto the environment the brain senses, just as the fetal environment responds to the maternal environment.

Thomas R. Collins/MDedge News

If food is plentiful, our hormones force us to eat until our bodies feel that there are enough fat stores to survive. Because of environmental influences such as highly processed food, preservatives, climate change, and regulation of temperature, our brains have decided that we need more adipose tissue than we did 50-100 years ago. It could be that an element in food has caused a dysfunction of the pathways that regulate our body weight, and most of us “defend” a higher body weight in this environment.

How to counteract that? Not easily. The ketogenic diet works temporarily just like any other diet where calorie intake is lower than usual. It seems to be agreeable to many people because they say they feel full after eating protein, fat, and perhaps some vegetables. Protein and fat are certainly more satiating than simple carbohydrates.

If strictly followed, a ketogenic diet will force the body to burn fat and go into ketosis. Without a source for glucose, the brain will burn ketones from fat stores. Owen and colleagues discovered this in 1969 when they did their now-famous studies of fasting in inpatients at Brigham and Women’s hospital, using IV amino acids to protect muscle mass.
 

Keto for life?

Is the ketogenic diet a healthy diet for the long term? That is a different question.

Of course not – we need high-fiber carbohydrate sources such as whole grains, fruits, and vegetables to keep the colon healthy and obtain the vitamins and minerals needed to make the Krebs cycle, or citric acid cycle, work at its best.

Why, then, are we promoting ketogenic diets for those with obesity and type 2 diabetes? Ketogenic or low-carbohydrate diets are easy to teach and can rapidly help patients lose weight and return their blood glucose, blood pressure, and other metabolic parameters to normal.

The patient will be instructed to avoid all highly processed foods. Studies have shown that highly processed foods, created to maximize flavor, “coerce” people to eat more calories than when presented with the same number of calories in unprocessed foods, a way to fool the brain.
 

Why are we fooling the brain?

We circumvent the natural satiety mechanisms that start with the gut. When we eat, our gastric fundus and intestinal stretch receptors start the process that informs the hypothalamus about food intake. Highly processed foods are usually devoid of fiber and volume, and pack in the calories in small volumes so that the stretch receptors are not activated until more calories are ingested. The study mentioned above developed two ad lib diets with the same number of calories, sugar, fat, and carbohydrate content – one ultraprocessed and the other unprocessed.

That explanation is just the tip of the iceberg, because a lot more than primitive stretch receptors is informing the brain. There are gut hormones that are secreted before and after meals, such as ghrelin, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and cholecystokinin (CCK), among a slew of others. These peptide hormones are all secreted from gut cells into the blood or vagus nerve, or both, and alert the brain that there is or is not enough food to maintain body weight at its set point.

It’s a highly regulated and precise system that regulates body weight for survival of the species in this environment. However, the environment has changed over the past 100 years but our genetic makeup for survival of the fittest has not. The mechanism of action for defense of a higher body weight set point in this new environment has not been elucidated as yet. Most likely, there are many players or instigators involved, such as food-supply changes, sedentary lifestyle, ambient temperature, fetal programming, air quality, and global warming and climate change, to name a few.

The goal of obesity researchers is to investigate the underlying mechanisms of the increased prevalence of obesity over the past 100 years. The goal of obesity medicine specialists is to treat obesity in adults and children, and to prevent obesity as much as possible with lifestyle change and medications that have been shown to help “reverse” the metabolic adaptation to this environment. Our newest GLP-1/GIP receptor agonists have been shown in animal models to hit several pathways that lead to obesity. They are not just appetite suppressants. Yes, they do modulate appetite and satiety, but they also affect energy expenditure. The body’s normal reaction to a lack of calorie intake is to reduce resting energy expenditure until body weight increases back to “set point levels.” These agonists prevent that metabolic adaptation. That is why they are true agents that can treat obesity – the disease.

Back to the ketogenic diet. The ketogenic diet can fool the brain temporarily by using protein and fat to elicit satiety with less food intake in calories. After a while, however, gut hormones and other factors begin to counteract the weight loss with a reduction in resting energy and total energy expenditure, and other metabolic measures, to get the body back to a certain body weight set point.

The ketogenic diet also can help dieters avoid ultra- and highly processed foods. In the end, any type of diet that lowers caloric intake will work for weight loss, but it’s the maintenance of that weight loss that makes a long-term difference, and that involves closing the metabolic gap that the body generates to defend fat mass. Understanding this pathophysiology will allow obesity medicine specialists to assist patients with obesity to lose weight and keep it off.

Dr. Apovian is in the department of medicine, division of endocrinology, diabetes, and hypertension, and codirector, Center for Weight Management and Wellness, Harvard Medical School, Boston. She disclosed ties with Altimmune, Cowen and Company, Currax Pharmaceuticals, EPG Communication Holdings, Gelesis Srl, L-Nutra, NeuroBo Pharmaceuticals, National Institutes of Health, Patient-Centered Outcomes Research Institute, GI Dynamics, and Novo Nordisk. A version of this article first appeared on Medscape.com.

Is the ketogenic diet the only way to lose weight? Of course not! Keep track of calories in vs. calories out and almost anyone can lose weight. The problem is keeping it off. To understand that, we need to look at metabolic adaptation and the biology of obesity.

Our bodies have a “set point” that is epigenetically latched onto the environment the brain senses, just as the fetal environment responds to the maternal environment.

Thomas R. Collins/MDedge News

If food is plentiful, our hormones force us to eat until our bodies feel that there are enough fat stores to survive. Because of environmental influences such as highly processed food, preservatives, climate change, and regulation of temperature, our brains have decided that we need more adipose tissue than we did 50-100 years ago. It could be that an element in food has caused a dysfunction of the pathways that regulate our body weight, and most of us “defend” a higher body weight in this environment.

How to counteract that? Not easily. The ketogenic diet works temporarily just like any other diet where calorie intake is lower than usual. It seems to be agreeable to many people because they say they feel full after eating protein, fat, and perhaps some vegetables. Protein and fat are certainly more satiating than simple carbohydrates.

If strictly followed, a ketogenic diet will force the body to burn fat and go into ketosis. Without a source for glucose, the brain will burn ketones from fat stores. Owen and colleagues discovered this in 1969 when they did their now-famous studies of fasting in inpatients at Brigham and Women’s hospital, using IV amino acids to protect muscle mass.
 

Keto for life?

Is the ketogenic diet a healthy diet for the long term? That is a different question.

Of course not – we need high-fiber carbohydrate sources such as whole grains, fruits, and vegetables to keep the colon healthy and obtain the vitamins and minerals needed to make the Krebs cycle, or citric acid cycle, work at its best.

Why, then, are we promoting ketogenic diets for those with obesity and type 2 diabetes? Ketogenic or low-carbohydrate diets are easy to teach and can rapidly help patients lose weight and return their blood glucose, blood pressure, and other metabolic parameters to normal.

The patient will be instructed to avoid all highly processed foods. Studies have shown that highly processed foods, created to maximize flavor, “coerce” people to eat more calories than when presented with the same number of calories in unprocessed foods, a way to fool the brain.
 

Why are we fooling the brain?

We circumvent the natural satiety mechanisms that start with the gut. When we eat, our gastric fundus and intestinal stretch receptors start the process that informs the hypothalamus about food intake. Highly processed foods are usually devoid of fiber and volume, and pack in the calories in small volumes so that the stretch receptors are not activated until more calories are ingested. The study mentioned above developed two ad lib diets with the same number of calories, sugar, fat, and carbohydrate content – one ultraprocessed and the other unprocessed.

That explanation is just the tip of the iceberg, because a lot more than primitive stretch receptors is informing the brain. There are gut hormones that are secreted before and after meals, such as ghrelin, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and cholecystokinin (CCK), among a slew of others. These peptide hormones are all secreted from gut cells into the blood or vagus nerve, or both, and alert the brain that there is or is not enough food to maintain body weight at its set point.

It’s a highly regulated and precise system that regulates body weight for survival of the species in this environment. However, the environment has changed over the past 100 years but our genetic makeup for survival of the fittest has not. The mechanism of action for defense of a higher body weight set point in this new environment has not been elucidated as yet. Most likely, there are many players or instigators involved, such as food-supply changes, sedentary lifestyle, ambient temperature, fetal programming, air quality, and global warming and climate change, to name a few.

The goal of obesity researchers is to investigate the underlying mechanisms of the increased prevalence of obesity over the past 100 years. The goal of obesity medicine specialists is to treat obesity in adults and children, and to prevent obesity as much as possible with lifestyle change and medications that have been shown to help “reverse” the metabolic adaptation to this environment. Our newest GLP-1/GIP receptor agonists have been shown in animal models to hit several pathways that lead to obesity. They are not just appetite suppressants. Yes, they do modulate appetite and satiety, but they also affect energy expenditure. The body’s normal reaction to a lack of calorie intake is to reduce resting energy expenditure until body weight increases back to “set point levels.” These agonists prevent that metabolic adaptation. That is why they are true agents that can treat obesity – the disease.

Back to the ketogenic diet. The ketogenic diet can fool the brain temporarily by using protein and fat to elicit satiety with less food intake in calories. After a while, however, gut hormones and other factors begin to counteract the weight loss with a reduction in resting energy and total energy expenditure, and other metabolic measures, to get the body back to a certain body weight set point.

The ketogenic diet also can help dieters avoid ultra- and highly processed foods. In the end, any type of diet that lowers caloric intake will work for weight loss, but it’s the maintenance of that weight loss that makes a long-term difference, and that involves closing the metabolic gap that the body generates to defend fat mass. Understanding this pathophysiology will allow obesity medicine specialists to assist patients with obesity to lose weight and keep it off.

Dr. Apovian is in the department of medicine, division of endocrinology, diabetes, and hypertension, and codirector, Center for Weight Management and Wellness, Harvard Medical School, Boston. She disclosed ties with Altimmune, Cowen and Company, Currax Pharmaceuticals, EPG Communication Holdings, Gelesis Srl, L-Nutra, NeuroBo Pharmaceuticals, National Institutes of Health, Patient-Centered Outcomes Research Institute, GI Dynamics, and Novo Nordisk. A version of this article first appeared on Medscape.com.

Is the ketogenic diet the only way to lose weight? Of course not! Keep track of calories in vs. calories out and almost anyone can lose weight. The problem is keeping it off. To understand that, we need to look at metabolic adaptation and the biology of obesity.

Our bodies have a “set point” that is epigenetically latched onto the environment the brain senses, just as the fetal environment responds to the maternal environment.

Thomas R. Collins/MDedge News

If food is plentiful, our hormones force us to eat until our bodies feel that there are enough fat stores to survive. Because of environmental influences such as highly processed food, preservatives, climate change, and regulation of temperature, our brains have decided that we need more adipose tissue than we did 50-100 years ago. It could be that an element in food has caused a dysfunction of the pathways that regulate our body weight, and most of us “defend” a higher body weight in this environment.

How to counteract that? Not easily. The ketogenic diet works temporarily just like any other diet where calorie intake is lower than usual. It seems to be agreeable to many people because they say they feel full after eating protein, fat, and perhaps some vegetables. Protein and fat are certainly more satiating than simple carbohydrates.

If strictly followed, a ketogenic diet will force the body to burn fat and go into ketosis. Without a source for glucose, the brain will burn ketones from fat stores. Owen and colleagues discovered this in 1969 when they did their now-famous studies of fasting in inpatients at Brigham and Women’s hospital, using IV amino acids to protect muscle mass.
 

Keto for life?

Is the ketogenic diet a healthy diet for the long term? That is a different question.

Of course not – we need high-fiber carbohydrate sources such as whole grains, fruits, and vegetables to keep the colon healthy and obtain the vitamins and minerals needed to make the Krebs cycle, or citric acid cycle, work at its best.

Why, then, are we promoting ketogenic diets for those with obesity and type 2 diabetes? Ketogenic or low-carbohydrate diets are easy to teach and can rapidly help patients lose weight and return their blood glucose, blood pressure, and other metabolic parameters to normal.

The patient will be instructed to avoid all highly processed foods. Studies have shown that highly processed foods, created to maximize flavor, “coerce” people to eat more calories than when presented with the same number of calories in unprocessed foods, a way to fool the brain.
 

Why are we fooling the brain?

We circumvent the natural satiety mechanisms that start with the gut. When we eat, our gastric fundus and intestinal stretch receptors start the process that informs the hypothalamus about food intake. Highly processed foods are usually devoid of fiber and volume, and pack in the calories in small volumes so that the stretch receptors are not activated until more calories are ingested. The study mentioned above developed two ad lib diets with the same number of calories, sugar, fat, and carbohydrate content – one ultraprocessed and the other unprocessed.

That explanation is just the tip of the iceberg, because a lot more than primitive stretch receptors is informing the brain. There are gut hormones that are secreted before and after meals, such as ghrelin, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and cholecystokinin (CCK), among a slew of others. These peptide hormones are all secreted from gut cells into the blood or vagus nerve, or both, and alert the brain that there is or is not enough food to maintain body weight at its set point.

It’s a highly regulated and precise system that regulates body weight for survival of the species in this environment. However, the environment has changed over the past 100 years but our genetic makeup for survival of the fittest has not. The mechanism of action for defense of a higher body weight set point in this new environment has not been elucidated as yet. Most likely, there are many players or instigators involved, such as food-supply changes, sedentary lifestyle, ambient temperature, fetal programming, air quality, and global warming and climate change, to name a few.

The goal of obesity researchers is to investigate the underlying mechanisms of the increased prevalence of obesity over the past 100 years. The goal of obesity medicine specialists is to treat obesity in adults and children, and to prevent obesity as much as possible with lifestyle change and medications that have been shown to help “reverse” the metabolic adaptation to this environment. Our newest GLP-1/GIP receptor agonists have been shown in animal models to hit several pathways that lead to obesity. They are not just appetite suppressants. Yes, they do modulate appetite and satiety, but they also affect energy expenditure. The body’s normal reaction to a lack of calorie intake is to reduce resting energy expenditure until body weight increases back to “set point levels.” These agonists prevent that metabolic adaptation. That is why they are true agents that can treat obesity – the disease.

Back to the ketogenic diet. The ketogenic diet can fool the brain temporarily by using protein and fat to elicit satiety with less food intake in calories. After a while, however, gut hormones and other factors begin to counteract the weight loss with a reduction in resting energy and total energy expenditure, and other metabolic measures, to get the body back to a certain body weight set point.

The ketogenic diet also can help dieters avoid ultra- and highly processed foods. In the end, any type of diet that lowers caloric intake will work for weight loss, but it’s the maintenance of that weight loss that makes a long-term difference, and that involves closing the metabolic gap that the body generates to defend fat mass. Understanding this pathophysiology will allow obesity medicine specialists to assist patients with obesity to lose weight and keep it off.

Dr. Apovian is in the department of medicine, division of endocrinology, diabetes, and hypertension, and codirector, Center for Weight Management and Wellness, Harvard Medical School, Boston. She disclosed ties with Altimmune, Cowen and Company, Currax Pharmaceuticals, EPG Communication Holdings, Gelesis Srl, L-Nutra, NeuroBo Pharmaceuticals, National Institutes of Health, Patient-Centered Outcomes Research Institute, GI Dynamics, and Novo Nordisk. A version of this article first appeared on Medscape.com.

Adults with rheumatoid arthritis or primary Sjogren’s syndrome plus interstitial lung disease had higher levels of systemic sclerosis–specific antibodies than those without lung disease, based on data from 101 individuals.

Systemic sclerosis (SSc) has been associated with the development of interstitial lung disease (ILD), but the prevalence of SSc autoantibodies in patients with rheumatoid arthritis (RA) and primary Sjogren’s syndrome (SS) has not been explored, wrote Vasilike Koulouri, MD, of Kapodistrian University of Athens, and colleagues.

In a study published in the Journal of Translational Autoimmunity, the researchers reviewed serum data from patients with RA and SS using immunoblot assays to determine the prevalence of SSc-specific and anti-Ro52 autoantibodies, both of which have been associated with ILD in SSc patients.

The study population included 28 RA patients with ILD, 32 RA patients without ILD, 9 primary SS patients with ILD, and 32 primary SS patients with no ILD. The mean age of the RA participants was 63.4 years, 70% were women, and the mean age at RA diagnosis was 50.2 years. The mean age of the primary SS group was 60.3 years, 87.8% were female, and the mean age at diagnosis was 52.7 years.

Overall, SSc-specific antibodies across all titers were detected more frequently in RA patients with ILD compared with those with no ILD, though not statistically significant (42.9% vs. 21.9%, P = .08). However, “This trend was mainly attributed to the statistically significant difference between the two groups at strong titers (25% vs. 3.1%, P = .01),” the researchers wrote. Notably, RA patients with strong titer SSc-specific antibodies showed an 11-fold increased risk for ILD, they added.

No significant differences appeared in the prevalence of SSc-specific or Ro52 autoantibodies between primary SS patients with and without ILD, which might be attributable in part to the increased prevalence of anticentromere antibodies in primary SS, the researchers said.

RA patients who were positive for SSc-specific antibodies at strong titers were significantly more likely to have respiratory abnormalities than those who were negative (87.5% vs. 47.2%, P = .04), but no such differences appeared in primary SS patients.

“Early detection of SSc antibodies could be important in clinical practice as it may mandate further diagnostic (for example, screening for pulmonary hypertension) and therapeutic approaches of these patients,” the researchers wrote in their discussion.

The study findings were limited by several factors, mainly the small sample size, but also the potential for false-positive results on antibody titers, lack of data on the clinical significance of medium autoantibody titers, and the lack of long-term follow-up data, the researchers noted.

However, the results suggest that many seropositive RA patients with evidence of ILD “may evolve to a clinically evident overlap of RA and SSc” that would benefit from targeted treatment, they concluded.

The study was supported by a grant from Novartis AG and by the Molecular Immunology and Clinical Applications Unit, Department of Physiology, School of Medicine, National and Kapodistrian University of Athens. The researchers had no financial conflicts to disclose.

Adults with rheumatoid arthritis or primary Sjogren’s syndrome plus interstitial lung disease had higher levels of systemic sclerosis–specific antibodies than those without lung disease, based on data from 101 individuals.

Systemic sclerosis (SSc) has been associated with the development of interstitial lung disease (ILD), but the prevalence of SSc autoantibodies in patients with rheumatoid arthritis (RA) and primary Sjogren’s syndrome (SS) has not been explored, wrote Vasilike Koulouri, MD, of Kapodistrian University of Athens, and colleagues.

In a study published in the Journal of Translational Autoimmunity, the researchers reviewed serum data from patients with RA and SS using immunoblot assays to determine the prevalence of SSc-specific and anti-Ro52 autoantibodies, both of which have been associated with ILD in SSc patients.

The study population included 28 RA patients with ILD, 32 RA patients without ILD, 9 primary SS patients with ILD, and 32 primary SS patients with no ILD. The mean age of the RA participants was 63.4 years, 70% were women, and the mean age at RA diagnosis was 50.2 years. The mean age of the primary SS group was 60.3 years, 87.8% were female, and the mean age at diagnosis was 52.7 years.

Overall, SSc-specific antibodies across all titers were detected more frequently in RA patients with ILD compared with those with no ILD, though not statistically significant (42.9% vs. 21.9%, P = .08). However, “This trend was mainly attributed to the statistically significant difference between the two groups at strong titers (25% vs. 3.1%, P = .01),” the researchers wrote. Notably, RA patients with strong titer SSc-specific antibodies showed an 11-fold increased risk for ILD, they added.

No significant differences appeared in the prevalence of SSc-specific or Ro52 autoantibodies between primary SS patients with and without ILD, which might be attributable in part to the increased prevalence of anticentromere antibodies in primary SS, the researchers said.

RA patients who were positive for SSc-specific antibodies at strong titers were significantly more likely to have respiratory abnormalities than those who were negative (87.5% vs. 47.2%, P = .04), but no such differences appeared in primary SS patients.

“Early detection of SSc antibodies could be important in clinical practice as it may mandate further diagnostic (for example, screening for pulmonary hypertension) and therapeutic approaches of these patients,” the researchers wrote in their discussion.

The study findings were limited by several factors, mainly the small sample size, but also the potential for false-positive results on antibody titers, lack of data on the clinical significance of medium autoantibody titers, and the lack of long-term follow-up data, the researchers noted.

However, the results suggest that many seropositive RA patients with evidence of ILD “may evolve to a clinically evident overlap of RA and SSc” that would benefit from targeted treatment, they concluded.

The study was supported by a grant from Novartis AG and by the Molecular Immunology and Clinical Applications Unit, Department of Physiology, School of Medicine, National and Kapodistrian University of Athens. The researchers had no financial conflicts to disclose.

Adults with rheumatoid arthritis or primary Sjogren’s syndrome plus interstitial lung disease had higher levels of systemic sclerosis–specific antibodies than those without lung disease, based on data from 101 individuals.

Systemic sclerosis (SSc) has been associated with the development of interstitial lung disease (ILD), but the prevalence of SSc autoantibodies in patients with rheumatoid arthritis (RA) and primary Sjogren’s syndrome (SS) has not been explored, wrote Vasilike Koulouri, MD, of Kapodistrian University of Athens, and colleagues.

In a study published in the Journal of Translational Autoimmunity, the researchers reviewed serum data from patients with RA and SS using immunoblot assays to determine the prevalence of SSc-specific and anti-Ro52 autoantibodies, both of which have been associated with ILD in SSc patients.

The study population included 28 RA patients with ILD, 32 RA patients without ILD, 9 primary SS patients with ILD, and 32 primary SS patients with no ILD. The mean age of the RA participants was 63.4 years, 70% were women, and the mean age at RA diagnosis was 50.2 years. The mean age of the primary SS group was 60.3 years, 87.8% were female, and the mean age at diagnosis was 52.7 years.

Overall, SSc-specific antibodies across all titers were detected more frequently in RA patients with ILD compared with those with no ILD, though not statistically significant (42.9% vs. 21.9%, P = .08). However, “This trend was mainly attributed to the statistically significant difference between the two groups at strong titers (25% vs. 3.1%, P = .01),” the researchers wrote. Notably, RA patients with strong titer SSc-specific antibodies showed an 11-fold increased risk for ILD, they added.

No significant differences appeared in the prevalence of SSc-specific or Ro52 autoantibodies between primary SS patients with and without ILD, which might be attributable in part to the increased prevalence of anticentromere antibodies in primary SS, the researchers said.

RA patients who were positive for SSc-specific antibodies at strong titers were significantly more likely to have respiratory abnormalities than those who were negative (87.5% vs. 47.2%, P = .04), but no such differences appeared in primary SS patients.

“Early detection of SSc antibodies could be important in clinical practice as it may mandate further diagnostic (for example, screening for pulmonary hypertension) and therapeutic approaches of these patients,” the researchers wrote in their discussion.

The study findings were limited by several factors, mainly the small sample size, but also the potential for false-positive results on antibody titers, lack of data on the clinical significance of medium autoantibody titers, and the lack of long-term follow-up data, the researchers noted.

However, the results suggest that many seropositive RA patients with evidence of ILD “may evolve to a clinically evident overlap of RA and SSc” that would benefit from targeted treatment, they concluded.

The study was supported by a grant from Novartis AG and by the Molecular Immunology and Clinical Applications Unit, Department of Physiology, School of Medicine, National and Kapodistrian University of Athens. The researchers had no financial conflicts to disclose.

Clinicians working within the U.S. health care system order CTs; it’s just what we do, and we do it a lot. This isn’t necessarily bad, but an inevitable byproduct is the pandemic of incidental findings. One underrecognized but frequent “incidentaloma” on CT is an interstitial lung abnormality (ILA). The Fleischner Society defines an ILA as honeycombing, traction bronchiectasis, parenchymal distortions, and reticular abnormalities that take up more than 5% of a particular lung zone in a patient without a clinical diagnosis of interstitial lung disease (ILD). In essence, ILAs are both a radiographic and a clinical diagnosis.

ILAs are common. Depending on population characteristics, ILAs occur at a prevalence of up to 10%. With the advent of lung cancer screening and advances in CT technology, we’re now inundated with detailed images of lung parenchyma in older smokers who are at high risk for respiratory disease. The resulting opportunity for early identification of disease is as exciting as the risk for overdiagnosis, excessive testing, and unnecessary treatment is frightening. Early diagnosis remains critical for preventing irreversible respiratory disease. But as with any disease process, when we attempt to detect pathology before it has become apparent, the line between benign change and true abnormality is blurred.

Such is the challenge with ILAs. Past studies have shown an association between ILAs and morbidity and mortality, but considerable uncertainty persists over what the ILAs represent and how they should be managed. A recent study published in the American Journal of Respiratory and Critical Care Medicine  provides some clarity. The authors used data from the COPDGene cohort to correlate ILAs with lung testing, and functional and respiratory outcomes. As with other studies, they found that approximately 10% of the COPDGene patients that they examined had ILAs on CT and half of those met their criteria for “suspected ILD.” Suspected ILD was defined radiographically (definite fibrosis) and on lung function testing (abnormal forced vital capacity [FVC] or diffusing capacity of the lungs for carbon monoxide [DLCO]). The patients with suspected ILD had worse clinical outcomes; being a Black individual, pack-years of smoking, and GOLD stage on spirometry were independently associated with suspected ILD.

This type of study is urgently needed. Given their high prevalence, we’re in dire need of a valid model for risk stratifying ILAs. The authors of this study have moved us closer, but we’ve still got a long way to go. The study has significant limitations. First, although patients with previous documentation of ILD were excluded from COPDGene, no formal, multidisciplinary assessment was performed; therefore, some of the patients labeled as having ILA probably had diagnosable ILD. Their possible inclusion would falsely increase the prevalence of clinically important ILAs and exaggerate the relationship between ILAs and clinical outcomes.

The rhetorical gymnastics performed throughout the paper are necessary yet problematic. “Suspected ILD” is not a recognized diagnosis and the definition is therefore arbitrary. To the extent that “suspected ILD” requires an abnormality on spirometry or DLCO, one could argue it’s the lung function changes and not the radiographic findings that are driving the differences. In fact, “suspected ILD” was defined by lung function more often than radiographic criteria (16% had definite fibrosis on CT, 57% had an abnormal FVC, and 67% had an abnormal DLCO). Patients with ILAs without suspected ILD had outcomes that weren’t statistically different from those with no ILAs at all, implying that the lung testing and not the ILA is the better discriminator. Regardless, this leads us back to where we started before this paper was published: ILAs require lung function testing and referral to a pulmonologist for proper risk stratification. An accompanying editorial highlights these and other limitations.

One particular problem that isn’t addressed by the authors or the editorial is their findings on race. The authors concluded that Black persons with ILAs are more likely to have “suspected ILD.” However, their definition suffers from an insidious form of incorporation bias generated by the way they handled their DLCO reference values. The Global Lung Function Initiative equations they used were derived exclusively from White persons. In accordance with the recent American Thoracic Society/European Respiratory Society (ATS/ERS) statement on lung testing, the authors did not apply a fixed correction factor to adjust for race. Without such an adjustment, Black persons would be biased toward having lower percent predicted values for DLCO. In short, self-identified Black individuals would be more likely to have a predicted DLCO of less than 70% and to therefore meet criteria for “suspected ILD.” The resulting effects on biologic plausibility, causal inference, and the strength of the relationship between “suspected ILD” and clinical outcomes will vary by whether the association between race and lung function is considered a product of inherent biologic variability or a result of external (socioeconomic and environmental) effects.

In summary, ILAs remain a challenge for radiologists, primary care providers, pulmonologists, and anyone else who orders a CT of the lungs. Despite its limitations, I believe the recently published paper pushes us forward conceptually. Perhaps its most important contribution is showing that 50% of ILAs are clinically insignificant by definition. This offers further reassurance that a subset of ILAs can be dismissed. Now, all we need is an easy, cost-effective, and efficient way to identify this subset.
 

Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington. He covers a wide range of topics in pulmonary, critical care, and sleep medicine. He disclosed ties to Metapharm Inc., CHEST College, and WebMD. A version of this article originally appeared on Medscape.com.

Clinicians working within the U.S. health care system order CTs; it’s just what we do, and we do it a lot. This isn’t necessarily bad, but an inevitable byproduct is the pandemic of incidental findings. One underrecognized but frequent “incidentaloma” on CT is an interstitial lung abnormality (ILA). The Fleischner Society defines an ILA as honeycombing, traction bronchiectasis, parenchymal distortions, and reticular abnormalities that take up more than 5% of a particular lung zone in a patient without a clinical diagnosis of interstitial lung disease (ILD). In essence, ILAs are both a radiographic and a clinical diagnosis.

ILAs are common. Depending on population characteristics, ILAs occur at a prevalence of up to 10%. With the advent of lung cancer screening and advances in CT technology, we’re now inundated with detailed images of lung parenchyma in older smokers who are at high risk for respiratory disease. The resulting opportunity for early identification of disease is as exciting as the risk for overdiagnosis, excessive testing, and unnecessary treatment is frightening. Early diagnosis remains critical for preventing irreversible respiratory disease. But as with any disease process, when we attempt to detect pathology before it has become apparent, the line between benign change and true abnormality is blurred.

Such is the challenge with ILAs. Past studies have shown an association between ILAs and morbidity and mortality, but considerable uncertainty persists over what the ILAs represent and how they should be managed. A recent study published in the American Journal of Respiratory and Critical Care Medicine  provides some clarity. The authors used data from the COPDGene cohort to correlate ILAs with lung testing, and functional and respiratory outcomes. As with other studies, they found that approximately 10% of the COPDGene patients that they examined had ILAs on CT and half of those met their criteria for “suspected ILD.” Suspected ILD was defined radiographically (definite fibrosis) and on lung function testing (abnormal forced vital capacity [FVC] or diffusing capacity of the lungs for carbon monoxide [DLCO]). The patients with suspected ILD had worse clinical outcomes; being a Black individual, pack-years of smoking, and GOLD stage on spirometry were independently associated with suspected ILD.

This type of study is urgently needed. Given their high prevalence, we’re in dire need of a valid model for risk stratifying ILAs. The authors of this study have moved us closer, but we’ve still got a long way to go. The study has significant limitations. First, although patients with previous documentation of ILD were excluded from COPDGene, no formal, multidisciplinary assessment was performed; therefore, some of the patients labeled as having ILA probably had diagnosable ILD. Their possible inclusion would falsely increase the prevalence of clinically important ILAs and exaggerate the relationship between ILAs and clinical outcomes.

The rhetorical gymnastics performed throughout the paper are necessary yet problematic. “Suspected ILD” is not a recognized diagnosis and the definition is therefore arbitrary. To the extent that “suspected ILD” requires an abnormality on spirometry or DLCO, one could argue it’s the lung function changes and not the radiographic findings that are driving the differences. In fact, “suspected ILD” was defined by lung function more often than radiographic criteria (16% had definite fibrosis on CT, 57% had an abnormal FVC, and 67% had an abnormal DLCO). Patients with ILAs without suspected ILD had outcomes that weren’t statistically different from those with no ILAs at all, implying that the lung testing and not the ILA is the better discriminator. Regardless, this leads us back to where we started before this paper was published: ILAs require lung function testing and referral to a pulmonologist for proper risk stratification. An accompanying editorial highlights these and other limitations.

One particular problem that isn’t addressed by the authors or the editorial is their findings on race. The authors concluded that Black persons with ILAs are more likely to have “suspected ILD.” However, their definition suffers from an insidious form of incorporation bias generated by the way they handled their DLCO reference values. The Global Lung Function Initiative equations they used were derived exclusively from White persons. In accordance with the recent American Thoracic Society/European Respiratory Society (ATS/ERS) statement on lung testing, the authors did not apply a fixed correction factor to adjust for race. Without such an adjustment, Black persons would be biased toward having lower percent predicted values for DLCO. In short, self-identified Black individuals would be more likely to have a predicted DLCO of less than 70% and to therefore meet criteria for “suspected ILD.” The resulting effects on biologic plausibility, causal inference, and the strength of the relationship between “suspected ILD” and clinical outcomes will vary by whether the association between race and lung function is considered a product of inherent biologic variability or a result of external (socioeconomic and environmental) effects.

In summary, ILAs remain a challenge for radiologists, primary care providers, pulmonologists, and anyone else who orders a CT of the lungs. Despite its limitations, I believe the recently published paper pushes us forward conceptually. Perhaps its most important contribution is showing that 50% of ILAs are clinically insignificant by definition. This offers further reassurance that a subset of ILAs can be dismissed. Now, all we need is an easy, cost-effective, and efficient way to identify this subset.
 

Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington. He covers a wide range of topics in pulmonary, critical care, and sleep medicine. He disclosed ties to Metapharm Inc., CHEST College, and WebMD. A version of this article originally appeared on Medscape.com.

Clinicians working within the U.S. health care system order CTs; it’s just what we do, and we do it a lot. This isn’t necessarily bad, but an inevitable byproduct is the pandemic of incidental findings. One underrecognized but frequent “incidentaloma” on CT is an interstitial lung abnormality (ILA). The Fleischner Society defines an ILA as honeycombing, traction bronchiectasis, parenchymal distortions, and reticular abnormalities that take up more than 5% of a particular lung zone in a patient without a clinical diagnosis of interstitial lung disease (ILD). In essence, ILAs are both a radiographic and a clinical diagnosis.

ILAs are common. Depending on population characteristics, ILAs occur at a prevalence of up to 10%. With the advent of lung cancer screening and advances in CT technology, we’re now inundated with detailed images of lung parenchyma in older smokers who are at high risk for respiratory disease. The resulting opportunity for early identification of disease is as exciting as the risk for overdiagnosis, excessive testing, and unnecessary treatment is frightening. Early diagnosis remains critical for preventing irreversible respiratory disease. But as with any disease process, when we attempt to detect pathology before it has become apparent, the line between benign change and true abnormality is blurred.

Such is the challenge with ILAs. Past studies have shown an association between ILAs and morbidity and mortality, but considerable uncertainty persists over what the ILAs represent and how they should be managed. A recent study published in the American Journal of Respiratory and Critical Care Medicine  provides some clarity. The authors used data from the COPDGene cohort to correlate ILAs with lung testing, and functional and respiratory outcomes. As with other studies, they found that approximately 10% of the COPDGene patients that they examined had ILAs on CT and half of those met their criteria for “suspected ILD.” Suspected ILD was defined radiographically (definite fibrosis) and on lung function testing (abnormal forced vital capacity [FVC] or diffusing capacity of the lungs for carbon monoxide [DLCO]). The patients with suspected ILD had worse clinical outcomes; being a Black individual, pack-years of smoking, and GOLD stage on spirometry were independently associated with suspected ILD.

This type of study is urgently needed. Given their high prevalence, we’re in dire need of a valid model for risk stratifying ILAs. The authors of this study have moved us closer, but we’ve still got a long way to go. The study has significant limitations. First, although patients with previous documentation of ILD were excluded from COPDGene, no formal, multidisciplinary assessment was performed; therefore, some of the patients labeled as having ILA probably had diagnosable ILD. Their possible inclusion would falsely increase the prevalence of clinically important ILAs and exaggerate the relationship between ILAs and clinical outcomes.

The rhetorical gymnastics performed throughout the paper are necessary yet problematic. “Suspected ILD” is not a recognized diagnosis and the definition is therefore arbitrary. To the extent that “suspected ILD” requires an abnormality on spirometry or DLCO, one could argue it’s the lung function changes and not the radiographic findings that are driving the differences. In fact, “suspected ILD” was defined by lung function more often than radiographic criteria (16% had definite fibrosis on CT, 57% had an abnormal FVC, and 67% had an abnormal DLCO). Patients with ILAs without suspected ILD had outcomes that weren’t statistically different from those with no ILAs at all, implying that the lung testing and not the ILA is the better discriminator. Regardless, this leads us back to where we started before this paper was published: ILAs require lung function testing and referral to a pulmonologist for proper risk stratification. An accompanying editorial highlights these and other limitations.

One particular problem that isn’t addressed by the authors or the editorial is their findings on race. The authors concluded that Black persons with ILAs are more likely to have “suspected ILD.” However, their definition suffers from an insidious form of incorporation bias generated by the way they handled their DLCO reference values. The Global Lung Function Initiative equations they used were derived exclusively from White persons. In accordance with the recent American Thoracic Society/European Respiratory Society (ATS/ERS) statement on lung testing, the authors did not apply a fixed correction factor to adjust for race. Without such an adjustment, Black persons would be biased toward having lower percent predicted values for DLCO. In short, self-identified Black individuals would be more likely to have a predicted DLCO of less than 70% and to therefore meet criteria for “suspected ILD.” The resulting effects on biologic plausibility, causal inference, and the strength of the relationship between “suspected ILD” and clinical outcomes will vary by whether the association between race and lung function is considered a product of inherent biologic variability or a result of external (socioeconomic and environmental) effects.

In summary, ILAs remain a challenge for radiologists, primary care providers, pulmonologists, and anyone else who orders a CT of the lungs. Despite its limitations, I believe the recently published paper pushes us forward conceptually. Perhaps its most important contribution is showing that 50% of ILAs are clinically insignificant by definition. This offers further reassurance that a subset of ILAs can be dismissed. Now, all we need is an easy, cost-effective, and efficient way to identify this subset.
 

Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington. He covers a wide range of topics in pulmonary, critical care, and sleep medicine. He disclosed ties to Metapharm Inc., CHEST College, and WebMD. A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Last week, a number of patients emailed me regarding their concerns about this phenomenon known as Ozempic face. I went on to read about what this meant. I live in Los Angeles, where most people appear to be on semaglutide (Ozempic). It’s the phenomenon where people lose weight relatively rapidly, making their faces thin out. Then what happens, apparently, is they look older because their face is more wrinkled and baggier. They might have to have further plastic surgery. I say that with slight sarcasm because of where I live.

I want to talk about what I think about this, living here where there’s a great pressure to prescribe semaglutide off label, and what I think about it for my patients with diabetes.

Historically, we haven’t had much in terms of effective medication for treating obesity, and frankly, now we do. We now have agents that are effective, that have relatively few side effects, and that have become part of what’s out there. People now want to use these agents, semaglutide, and there’s been a great need for these agents.

The problem, however, is twofold. One, as we all know, is that it has basically caused a shortage of medication for treating our patients who actually have type 2 diabetes and really need these medications to manage their disease. Then we have people who want these medications who can’t pay for them. Insurance doesn’t cover obesity medications, which is problematic and actually quite frustrating for people who, I think, really would benefit from using these medications.

What I tell people, frankly, is that until I have enough supply for my patients with type 2 diabetes, who need these agents to control their blood sugars, I want to keep this class of drugs available to them. I also hope we’re able to expand it more and more with improving insurance coverage – and that’s a big if, if you ask me – both for people who have prediabetes and for patients who are overweight and obese, because I think it’s really hard for people to lose weight.

It’s frustrating, and for many people, being overweight and obese causes all sorts of other health issues, not only diabetes. I believe that these drugs are both safe and effective and should be more available. I do think we need to be careful in terms of who we prescribe them to, at least at the moment. Hopefully, we’ll be able to expand their use.

Anything that can encourage our population to lose weight and maintain that weight loss is very important. We need to couple weight loss medications with lifestyle interventions. I think people can out-eat any medication; therefore, it’s very important to encourage our patients to eat better, to exercise more, and to do all the other things they need to do to reduce their risks for other comorbidities.

I am incredibly happy to have these newer agents on the market. I tell my patients – at least those who have diabetes – that they have to accept looking a little bit too thin for the benefits that we can see in using these medications.

Thank you.

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations. She has ties with Abbott Diabetes Care, AstraZeneca Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen. A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Last week, a number of patients emailed me regarding their concerns about this phenomenon known as Ozempic face. I went on to read about what this meant. I live in Los Angeles, where most people appear to be on semaglutide (Ozempic). It’s the phenomenon where people lose weight relatively rapidly, making their faces thin out. Then what happens, apparently, is they look older because their face is more wrinkled and baggier. They might have to have further plastic surgery. I say that with slight sarcasm because of where I live.

I want to talk about what I think about this, living here where there’s a great pressure to prescribe semaglutide off label, and what I think about it for my patients with diabetes.

Historically, we haven’t had much in terms of effective medication for treating obesity, and frankly, now we do. We now have agents that are effective, that have relatively few side effects, and that have become part of what’s out there. People now want to use these agents, semaglutide, and there’s been a great need for these agents.

The problem, however, is twofold. One, as we all know, is that it has basically caused a shortage of medication for treating our patients who actually have type 2 diabetes and really need these medications to manage their disease. Then we have people who want these medications who can’t pay for them. Insurance doesn’t cover obesity medications, which is problematic and actually quite frustrating for people who, I think, really would benefit from using these medications.

What I tell people, frankly, is that until I have enough supply for my patients with type 2 diabetes, who need these agents to control their blood sugars, I want to keep this class of drugs available to them. I also hope we’re able to expand it more and more with improving insurance coverage – and that’s a big if, if you ask me – both for people who have prediabetes and for patients who are overweight and obese, because I think it’s really hard for people to lose weight.

It’s frustrating, and for many people, being overweight and obese causes all sorts of other health issues, not only diabetes. I believe that these drugs are both safe and effective and should be more available. I do think we need to be careful in terms of who we prescribe them to, at least at the moment. Hopefully, we’ll be able to expand their use.

Anything that can encourage our population to lose weight and maintain that weight loss is very important. We need to couple weight loss medications with lifestyle interventions. I think people can out-eat any medication; therefore, it’s very important to encourage our patients to eat better, to exercise more, and to do all the other things they need to do to reduce their risks for other comorbidities.

I am incredibly happy to have these newer agents on the market. I tell my patients – at least those who have diabetes – that they have to accept looking a little bit too thin for the benefits that we can see in using these medications.

Thank you.

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations. She has ties with Abbott Diabetes Care, AstraZeneca Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen. A version of this article originally appeared on Medscape.com.

This transcript has been edited for clarity.

Last week, a number of patients emailed me regarding their concerns about this phenomenon known as Ozempic face. I went on to read about what this meant. I live in Los Angeles, where most people appear to be on semaglutide (Ozempic). It’s the phenomenon where people lose weight relatively rapidly, making their faces thin out. Then what happens, apparently, is they look older because their face is more wrinkled and baggier. They might have to have further plastic surgery. I say that with slight sarcasm because of where I live.

I want to talk about what I think about this, living here where there’s a great pressure to prescribe semaglutide off label, and what I think about it for my patients with diabetes.

Historically, we haven’t had much in terms of effective medication for treating obesity, and frankly, now we do. We now have agents that are effective, that have relatively few side effects, and that have become part of what’s out there. People now want to use these agents, semaglutide, and there’s been a great need for these agents.

The problem, however, is twofold. One, as we all know, is that it has basically caused a shortage of medication for treating our patients who actually have type 2 diabetes and really need these medications to manage their disease. Then we have people who want these medications who can’t pay for them. Insurance doesn’t cover obesity medications, which is problematic and actually quite frustrating for people who, I think, really would benefit from using these medications.

What I tell people, frankly, is that until I have enough supply for my patients with type 2 diabetes, who need these agents to control their blood sugars, I want to keep this class of drugs available to them. I also hope we’re able to expand it more and more with improving insurance coverage – and that’s a big if, if you ask me – both for people who have prediabetes and for patients who are overweight and obese, because I think it’s really hard for people to lose weight.

It’s frustrating, and for many people, being overweight and obese causes all sorts of other health issues, not only diabetes. I believe that these drugs are both safe and effective and should be more available. I do think we need to be careful in terms of who we prescribe them to, at least at the moment. Hopefully, we’ll be able to expand their use.

Anything that can encourage our population to lose weight and maintain that weight loss is very important. We need to couple weight loss medications with lifestyle interventions. I think people can out-eat any medication; therefore, it’s very important to encourage our patients to eat better, to exercise more, and to do all the other things they need to do to reduce their risks for other comorbidities.

I am incredibly happy to have these newer agents on the market. I tell my patients – at least those who have diabetes – that they have to accept looking a little bit too thin for the benefits that we can see in using these medications.

Thank you.

Dr. Peters is professor of medicine at the University of Southern California, Los Angeles, and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations. She has ties with Abbott Diabetes Care, AstraZeneca Becton Dickinson, Boehringer Ingelheim Pharmaceuticals, Dexcom, Eli Lilly, Lexicon Pharmaceuticals, Livongo, MannKind Corporation, Medscape, Merck, Novo Nordisk, Omada Health, OptumHealth, Sanofi, and Zafgen. A version of this article originally appeared on Medscape.com.

Posoleucel, an investigational off-the-shelf T-cell therapy, showed promising safety and efficacy for eradicating multiple viruses in a phase 2 study of patients who previously underwent allogeneic stem cell transplant (allo-SCT).

Of 58 adult and pediatric patients with a total of 70 viral infections at the time of enrollment in the open-label trial, 55 (95%) had a treatment response within 6 weeks of infusion with posoleucel, and the amount of circulating virus was reduced by an average of 97%, Thomas Pfeiffer, MD, and colleagues reported.

In 12 patients who had more than one viral infection, 10 (83%) had a response against each of the viruses, researchers noted.

The responses were defined as a reduction of viral load to normal range with complete response, or as a viral load reduction of at least 50 percent or a partial response.

The findings were published online in Clinical Cancer Research.

Specifically, the treatment evoked responses to adenovirus in 83% of 12 affected patients, BK virus in all 27 affected patients, CMV in 96% of 24 affected patients, Epstein-Barr virus in both affected patients, and human herpes virus in 75% of 4 patients. Additionally, one patient with JC virus experienced initial stabilization of viral symptoms, although the symptoms ultimately progressed, and the patient died.

“The key finding is that 95% of patients whose infections had been refractory to conventional therapies responded to posoleucel with corresponding reductions in viral load and with limited rates of GvHD [graft-versus-host disease],” Dr. Pfeiffer, a pediatric cancer specialist at Washington University in St. Louis, explained in a prepared statement. “Overall, posoleucel was found to be very effective and had a favorable safety profile in a highly vulnerable patient population.”

“Another exciting observation from this study was that posoleucel could be administered within 24 hours in some cases, with symptom resolution in a matter of days in some patients,” added senior author Bilal Omer, MD, a pediatric hematologist-oncologist at Texas Children’s Hospital and Baylor College of Medicine, Houston. “It was quite impressive how quickly patients could be treated.”

Dr. Omer explained that currently available treatments for patients who develop viral infections after allo-SCT have numerous limitations, including toxicities such as myelosuppression or kidney injury and limited efficacy.

In this study, 13 patients (22% percent) reported acute GvHD, but only 4 of the cases were considered de novo cases; 9 patients had been diagnosed with GvHD prior to posoleucel treatment. The most common GvHD symptoms were skin flares, which were successfully treated in the majority of cases, Dr. Omer explained.

No patients experienced cytokine release syndrome.

“The ability to target six viruses with a single therapy would be beneficial for patients with multiple viral infections,” he said, adding that posoleucel is the first T-cell therapy in development for BK virus, which can cause severe bladder infections.

Posoleucel utilizes healthy donor T cells rather than the patient’s or transplant donor’s T cells, which circumvents the lengthy development process of more customized therapies and allows for earlier treatment of viral infections, he noted.

The investigators are currently evaluating posoleucel in randomized phase 3 clinical trials to confirm these findings.

This study was supported by the National Heart, Lung, and Blood Institute Production Assistance for Cellular Therapies; Conquer Cancer Foundation/American Society for Clinical Oncology; the Dan L. Duncan Comprehensive Cancer Center; and the National Institutes of Health.

Dr. Omer disclosed pending patent applications for engineered T-cell therapies unrelated to this study, and he has received research funding from AlloVir, which manufactures posoleucel. Dr. Pfeiffer declared no conflicts of interest.
 

Posoleucel, an investigational off-the-shelf T-cell therapy, showed promising safety and efficacy for eradicating multiple viruses in a phase 2 study of patients who previously underwent allogeneic stem cell transplant (allo-SCT).

Of 58 adult and pediatric patients with a total of 70 viral infections at the time of enrollment in the open-label trial, 55 (95%) had a treatment response within 6 weeks of infusion with posoleucel, and the amount of circulating virus was reduced by an average of 97%, Thomas Pfeiffer, MD, and colleagues reported.

In 12 patients who had more than one viral infection, 10 (83%) had a response against each of the viruses, researchers noted.

The responses were defined as a reduction of viral load to normal range with complete response, or as a viral load reduction of at least 50 percent or a partial response.

The findings were published online in Clinical Cancer Research.

Specifically, the treatment evoked responses to adenovirus in 83% of 12 affected patients, BK virus in all 27 affected patients, CMV in 96% of 24 affected patients, Epstein-Barr virus in both affected patients, and human herpes virus in 75% of 4 patients. Additionally, one patient with JC virus experienced initial stabilization of viral symptoms, although the symptoms ultimately progressed, and the patient died.

“The key finding is that 95% of patients whose infections had been refractory to conventional therapies responded to posoleucel with corresponding reductions in viral load and with limited rates of GvHD [graft-versus-host disease],” Dr. Pfeiffer, a pediatric cancer specialist at Washington University in St. Louis, explained in a prepared statement. “Overall, posoleucel was found to be very effective and had a favorable safety profile in a highly vulnerable patient population.”

“Another exciting observation from this study was that posoleucel could be administered within 24 hours in some cases, with symptom resolution in a matter of days in some patients,” added senior author Bilal Omer, MD, a pediatric hematologist-oncologist at Texas Children’s Hospital and Baylor College of Medicine, Houston. “It was quite impressive how quickly patients could be treated.”

Dr. Omer explained that currently available treatments for patients who develop viral infections after allo-SCT have numerous limitations, including toxicities such as myelosuppression or kidney injury and limited efficacy.

In this study, 13 patients (22% percent) reported acute GvHD, but only 4 of the cases were considered de novo cases; 9 patients had been diagnosed with GvHD prior to posoleucel treatment. The most common GvHD symptoms were skin flares, which were successfully treated in the majority of cases, Dr. Omer explained.

No patients experienced cytokine release syndrome.

“The ability to target six viruses with a single therapy would be beneficial for patients with multiple viral infections,” he said, adding that posoleucel is the first T-cell therapy in development for BK virus, which can cause severe bladder infections.

Posoleucel utilizes healthy donor T cells rather than the patient’s or transplant donor’s T cells, which circumvents the lengthy development process of more customized therapies and allows for earlier treatment of viral infections, he noted.

The investigators are currently evaluating posoleucel in randomized phase 3 clinical trials to confirm these findings.

This study was supported by the National Heart, Lung, and Blood Institute Production Assistance for Cellular Therapies; Conquer Cancer Foundation/American Society for Clinical Oncology; the Dan L. Duncan Comprehensive Cancer Center; and the National Institutes of Health.

Dr. Omer disclosed pending patent applications for engineered T-cell therapies unrelated to this study, and he has received research funding from AlloVir, which manufactures posoleucel. Dr. Pfeiffer declared no conflicts of interest.
 

Posoleucel, an investigational off-the-shelf T-cell therapy, showed promising safety and efficacy for eradicating multiple viruses in a phase 2 study of patients who previously underwent allogeneic stem cell transplant (allo-SCT).

Of 58 adult and pediatric patients with a total of 70 viral infections at the time of enrollment in the open-label trial, 55 (95%) had a treatment response within 6 weeks of infusion with posoleucel, and the amount of circulating virus was reduced by an average of 97%, Thomas Pfeiffer, MD, and colleagues reported.

In 12 patients who had more than one viral infection, 10 (83%) had a response against each of the viruses, researchers noted.

The responses were defined as a reduction of viral load to normal range with complete response, or as a viral load reduction of at least 50 percent or a partial response.

The findings were published online in Clinical Cancer Research.

Specifically, the treatment evoked responses to adenovirus in 83% of 12 affected patients, BK virus in all 27 affected patients, CMV in 96% of 24 affected patients, Epstein-Barr virus in both affected patients, and human herpes virus in 75% of 4 patients. Additionally, one patient with JC virus experienced initial stabilization of viral symptoms, although the symptoms ultimately progressed, and the patient died.

“The key finding is that 95% of patients whose infections had been refractory to conventional therapies responded to posoleucel with corresponding reductions in viral load and with limited rates of GvHD [graft-versus-host disease],” Dr. Pfeiffer, a pediatric cancer specialist at Washington University in St. Louis, explained in a prepared statement. “Overall, posoleucel was found to be very effective and had a favorable safety profile in a highly vulnerable patient population.”

“Another exciting observation from this study was that posoleucel could be administered within 24 hours in some cases, with symptom resolution in a matter of days in some patients,” added senior author Bilal Omer, MD, a pediatric hematologist-oncologist at Texas Children’s Hospital and Baylor College of Medicine, Houston. “It was quite impressive how quickly patients could be treated.”

Dr. Omer explained that currently available treatments for patients who develop viral infections after allo-SCT have numerous limitations, including toxicities such as myelosuppression or kidney injury and limited efficacy.

In this study, 13 patients (22% percent) reported acute GvHD, but only 4 of the cases were considered de novo cases; 9 patients had been diagnosed with GvHD prior to posoleucel treatment. The most common GvHD symptoms were skin flares, which were successfully treated in the majority of cases, Dr. Omer explained.

No patients experienced cytokine release syndrome.

“The ability to target six viruses with a single therapy would be beneficial for patients with multiple viral infections,” he said, adding that posoleucel is the first T-cell therapy in development for BK virus, which can cause severe bladder infections.

Posoleucel utilizes healthy donor T cells rather than the patient’s or transplant donor’s T cells, which circumvents the lengthy development process of more customized therapies and allows for earlier treatment of viral infections, he noted.

The investigators are currently evaluating posoleucel in randomized phase 3 clinical trials to confirm these findings.

This study was supported by the National Heart, Lung, and Blood Institute Production Assistance for Cellular Therapies; Conquer Cancer Foundation/American Society for Clinical Oncology; the Dan L. Duncan Comprehensive Cancer Center; and the National Institutes of Health.

Dr. Omer disclosed pending patent applications for engineered T-cell therapies unrelated to this study, and he has received research funding from AlloVir, which manufactures posoleucel. Dr. Pfeiffer declared no conflicts of interest.
 

Frequent visits to green spaces such as parks and community gardens are associated with a reduced use of certain prescription medications among city dwellers, a new analysis suggests.

In a cross-sectional cohort study, frequent green space visits were associated with less frequent use of psychotropic, antihypertensive, and asthma medications in urban environments.

Viewing green or so called “blue” spaces (views of lakes, rivers, or other water views) from the home was not associated with reduced medication use.

Flickr-Rickr [CC BY-SA 2.0](http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons

Nature exposure a timely topic

Exposure to natural environments is thought to be beneficial for human health, but the evidence is inconsistent, Dr. Turunen said.

“The potential health benefits of nature exposure is a very timely topic in environmental epidemiology. Scientific evidence indicates that residential exposure to greenery and water bodies might be beneficial, especially for mental, cardiovascular, and respiratory health, but the findings are partly inconsistent and thus, more detailed information is needed,” she said.

In the current cross-sectional study, the investigators surveyed 16,000 residents of three urban areas in Finland – Helsinki, Espoo, and Vantaa – over the period of 12 months from 2015 to 2016, about their exposure to green and blue spaces.

Of this number, 43% responded, resulting in 7,321 participants.

In the questionnaire, green areas were defined as forests, parks, fields, meadows, boglands, and rocks, as well as any playgrounds or playing fields within those areas, and blue areas were defined as sea, lakes, and rivers. 

Residents were asked about their use of anxiolytics, hypnotics, antidepressants, antihypertensives, and asthma medication within the past 7 to 52 weeks.

They were also asked if they had any green and blue views from any of the windows of their home, and if so, how often did they look out of those windows, selecting “seldom” to “often.”

They were also asked about how much time they spent outdoors in green spaces during the months of May and September. If so, did they spend any of that time exercising? Options ranged from never to five or more times a week.

In addition, amounts of residential green and blue spaces located within a 1 km radius of the respondents’ homes were assessed from land use and land cover data.

Covariates included health behaviors, outdoor air pollution and noise, and socioeconomic status, including household income and educational attainment.

Results showed that the presence of green and blue spaces at home, and the amount of time spent viewing them, had no association with the use of the prescribed medicines.

However, greater frequency of green space visits was associated with lower odds of using the medications surveyed.

For psychotropic medications, the odds ratios were 0.67 (95% confidence interval, 0.55-0.82) for 3-4 times per week and 0.78 (95% CI, 0.63-0.96) for 5 or more times per week.

For antihypertensive meds, the ORs were 0.64 (95% CI, 0.52-0.78) for 3-4 times per week and 0.59 (95% CI, 0.48-0.74) for 5 or more times per week.

For asthma medications, the ORs were 0.74 (95% CI, 0.58-0.94) for 3-4 times per week and 0.76 (95% CI, 0.59-0.99) for 5 or more times per week.

The observed associations were attenuated by body mass index.

“We observed that those who reported visiting green spaces often had a slightly lower BMI than those who visited green spaces less often,” Dr. Turunen said. However, no consistent interactions with socioeconomic status indicators were observed.

“We are hoping to see new results from different countries and different settings,” she noted. “Longitudinal studies, especially, are needed. In epidemiology, a large body of consistent evidence is needed to draw strong conclusions and to make recommendations.”
 

Evidence mounts on the benefits of nature

There is growing evidence that exposure to nature could benefit human health, especially mental and cardiovascular health, says Jochem Klompmaker, PhD, a postdoctoral researcher in the department of environmental health at the Harvard T.H. Chan School of Public Health, Boston.

Dr. Klompmaker has researched the association between exposure to green spaces and health outcomes related to neurological diseases.

In a study recently published in JAMA Network Open, and reported by this news organization, Dr. Klompmaker and his team found that among a large cohort of about 6.7 million fee-for-service Medicare beneficiaries in the United States aged 65 or older, living in areas rich with greenery, parks, and waterways was associated with fewer hospitalizations for certain neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and related dementias.

Commenting on the current study, Dr. Klompmaker noted its strengths.

“A particular strength of this study is that they used data about the amount of green and blue spaces around the residential addresses of the participants, data about green space visit frequency, and data about green and blue views from home. Most other studies only have data about the amount of green and blue spaces in general,” he said.

“The strong protective associations of frequency of green space visits make sense to me and indicate the importance of one’s actual nature exposure,” he added. “Like the results of our study, these results provide clinicians with more evidence of the importance of being close to nature and of encouraging patients to take more walks. If they live near a park, that could be a good place to be more physically active and reduce stress levels.”

The study was supported by the Academy of Finland and the Ministry of the Environment. Dr. Turunen and Dr. Klompmaker report no relevant financial relationships.

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

Frequent visits to green spaces such as parks and community gardens are associated with a reduced use of certain prescription medications among city dwellers, a new analysis suggests.

In a cross-sectional cohort study, frequent green space visits were associated with less frequent use of psychotropic, antihypertensive, and asthma medications in urban environments.

Viewing green or so called “blue” spaces (views of lakes, rivers, or other water views) from the home was not associated with reduced medication use.

Flickr-Rickr [CC BY-SA 2.0](http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons

Nature exposure a timely topic

Exposure to natural environments is thought to be beneficial for human health, but the evidence is inconsistent, Dr. Turunen said.

“The potential health benefits of nature exposure is a very timely topic in environmental epidemiology. Scientific evidence indicates that residential exposure to greenery and water bodies might be beneficial, especially for mental, cardiovascular, and respiratory health, but the findings are partly inconsistent and thus, more detailed information is needed,” she said.

In the current cross-sectional study, the investigators surveyed 16,000 residents of three urban areas in Finland – Helsinki, Espoo, and Vantaa – over the period of 12 months from 2015 to 2016, about their exposure to green and blue spaces.

Of this number, 43% responded, resulting in 7,321 participants.

In the questionnaire, green areas were defined as forests, parks, fields, meadows, boglands, and rocks, as well as any playgrounds or playing fields within those areas, and blue areas were defined as sea, lakes, and rivers. 

Residents were asked about their use of anxiolytics, hypnotics, antidepressants, antihypertensives, and asthma medication within the past 7 to 52 weeks.

They were also asked if they had any green and blue views from any of the windows of their home, and if so, how often did they look out of those windows, selecting “seldom” to “often.”

They were also asked about how much time they spent outdoors in green spaces during the months of May and September. If so, did they spend any of that time exercising? Options ranged from never to five or more times a week.

In addition, amounts of residential green and blue spaces located within a 1 km radius of the respondents’ homes were assessed from land use and land cover data.

Covariates included health behaviors, outdoor air pollution and noise, and socioeconomic status, including household income and educational attainment.

Results showed that the presence of green and blue spaces at home, and the amount of time spent viewing them, had no association with the use of the prescribed medicines.

However, greater frequency of green space visits was associated with lower odds of using the medications surveyed.

For psychotropic medications, the odds ratios were 0.67 (95% confidence interval, 0.55-0.82) for 3-4 times per week and 0.78 (95% CI, 0.63-0.96) for 5 or more times per week.

For antihypertensive meds, the ORs were 0.64 (95% CI, 0.52-0.78) for 3-4 times per week and 0.59 (95% CI, 0.48-0.74) for 5 or more times per week.

For asthma medications, the ORs were 0.74 (95% CI, 0.58-0.94) for 3-4 times per week and 0.76 (95% CI, 0.59-0.99) for 5 or more times per week.

The observed associations were attenuated by body mass index.

“We observed that those who reported visiting green spaces often had a slightly lower BMI than those who visited green spaces less often,” Dr. Turunen said. However, no consistent interactions with socioeconomic status indicators were observed.

“We are hoping to see new results from different countries and different settings,” she noted. “Longitudinal studies, especially, are needed. In epidemiology, a large body of consistent evidence is needed to draw strong conclusions and to make recommendations.”
 

Evidence mounts on the benefits of nature

There is growing evidence that exposure to nature could benefit human health, especially mental and cardiovascular health, says Jochem Klompmaker, PhD, a postdoctoral researcher in the department of environmental health at the Harvard T.H. Chan School of Public Health, Boston.

Dr. Klompmaker has researched the association between exposure to green spaces and health outcomes related to neurological diseases.

In a study recently published in JAMA Network Open, and reported by this news organization, Dr. Klompmaker and his team found that among a large cohort of about 6.7 million fee-for-service Medicare beneficiaries in the United States aged 65 or older, living in areas rich with greenery, parks, and waterways was associated with fewer hospitalizations for certain neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and related dementias.

Commenting on the current study, Dr. Klompmaker noted its strengths.

“A particular strength of this study is that they used data about the amount of green and blue spaces around the residential addresses of the participants, data about green space visit frequency, and data about green and blue views from home. Most other studies only have data about the amount of green and blue spaces in general,” he said.

“The strong protective associations of frequency of green space visits make sense to me and indicate the importance of one’s actual nature exposure,” he added. “Like the results of our study, these results provide clinicians with more evidence of the importance of being close to nature and of encouraging patients to take more walks. If they live near a park, that could be a good place to be more physically active and reduce stress levels.”

The study was supported by the Academy of Finland and the Ministry of the Environment. Dr. Turunen and Dr. Klompmaker report no relevant financial relationships.

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

Frequent visits to green spaces such as parks and community gardens are associated with a reduced use of certain prescription medications among city dwellers, a new analysis suggests.

In a cross-sectional cohort study, frequent green space visits were associated with less frequent use of psychotropic, antihypertensive, and asthma medications in urban environments.

Viewing green or so called “blue” spaces (views of lakes, rivers, or other water views) from the home was not associated with reduced medication use.

Flickr-Rickr [CC BY-SA 2.0](http://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons

Nature exposure a timely topic

Exposure to natural environments is thought to be beneficial for human health, but the evidence is inconsistent, Dr. Turunen said.

“The potential health benefits of nature exposure is a very timely topic in environmental epidemiology. Scientific evidence indicates that residential exposure to greenery and water bodies might be beneficial, especially for mental, cardiovascular, and respiratory health, but the findings are partly inconsistent and thus, more detailed information is needed,” she said.

In the current cross-sectional study, the investigators surveyed 16,000 residents of three urban areas in Finland – Helsinki, Espoo, and Vantaa – over the period of 12 months from 2015 to 2016, about their exposure to green and blue spaces.

Of this number, 43% responded, resulting in 7,321 participants.

In the questionnaire, green areas were defined as forests, parks, fields, meadows, boglands, and rocks, as well as any playgrounds or playing fields within those areas, and blue areas were defined as sea, lakes, and rivers. 

Residents were asked about their use of anxiolytics, hypnotics, antidepressants, antihypertensives, and asthma medication within the past 7 to 52 weeks.

They were also asked if they had any green and blue views from any of the windows of their home, and if so, how often did they look out of those windows, selecting “seldom” to “often.”

They were also asked about how much time they spent outdoors in green spaces during the months of May and September. If so, did they spend any of that time exercising? Options ranged from never to five or more times a week.

In addition, amounts of residential green and blue spaces located within a 1 km radius of the respondents’ homes were assessed from land use and land cover data.

Covariates included health behaviors, outdoor air pollution and noise, and socioeconomic status, including household income and educational attainment.

Results showed that the presence of green and blue spaces at home, and the amount of time spent viewing them, had no association with the use of the prescribed medicines.

However, greater frequency of green space visits was associated with lower odds of using the medications surveyed.

For psychotropic medications, the odds ratios were 0.67 (95% confidence interval, 0.55-0.82) for 3-4 times per week and 0.78 (95% CI, 0.63-0.96) for 5 or more times per week.

For antihypertensive meds, the ORs were 0.64 (95% CI, 0.52-0.78) for 3-4 times per week and 0.59 (95% CI, 0.48-0.74) for 5 or more times per week.

For asthma medications, the ORs were 0.74 (95% CI, 0.58-0.94) for 3-4 times per week and 0.76 (95% CI, 0.59-0.99) for 5 or more times per week.

The observed associations were attenuated by body mass index.

“We observed that those who reported visiting green spaces often had a slightly lower BMI than those who visited green spaces less often,” Dr. Turunen said. However, no consistent interactions with socioeconomic status indicators were observed.

“We are hoping to see new results from different countries and different settings,” she noted. “Longitudinal studies, especially, are needed. In epidemiology, a large body of consistent evidence is needed to draw strong conclusions and to make recommendations.”
 

Evidence mounts on the benefits of nature

There is growing evidence that exposure to nature could benefit human health, especially mental and cardiovascular health, says Jochem Klompmaker, PhD, a postdoctoral researcher in the department of environmental health at the Harvard T.H. Chan School of Public Health, Boston.

Dr. Klompmaker has researched the association between exposure to green spaces and health outcomes related to neurological diseases.

In a study recently published in JAMA Network Open, and reported by this news organization, Dr. Klompmaker and his team found that among a large cohort of about 6.7 million fee-for-service Medicare beneficiaries in the United States aged 65 or older, living in areas rich with greenery, parks, and waterways was associated with fewer hospitalizations for certain neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and related dementias.

Commenting on the current study, Dr. Klompmaker noted its strengths.

“A particular strength of this study is that they used data about the amount of green and blue spaces around the residential addresses of the participants, data about green space visit frequency, and data about green and blue views from home. Most other studies only have data about the amount of green and blue spaces in general,” he said.

“The strong protective associations of frequency of green space visits make sense to me and indicate the importance of one’s actual nature exposure,” he added. “Like the results of our study, these results provide clinicians with more evidence of the importance of being close to nature and of encouraging patients to take more walks. If they live near a park, that could be a good place to be more physically active and reduce stress levels.”

The study was supported by the Academy of Finland and the Ministry of the Environment. Dr. Turunen and Dr. Klompmaker report no relevant financial relationships.

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

Two-thirds of children who underwent genetic testing in the pediatric intensive care unit showed a genetic variant, and a third of these children received changes in care as a result, according to a new study presented at the Society of Critical Care Medicine’s 2023 Critical Care Congress.

“We have had a lot of success using genome sequencing to help not only with diagnosis, but also changes in management,” lead author Katherine Rodriguez, MD, a pediatric critical care fellow physician at Rady Children’s Hospital, San Diego, told this news organization.

However, data on the use of rapid whole genome sequencing (rWGS) in the pediatric intensive care unit (PICU) are limited, and data from multiple institutions are lacking, Dr. Rodriguez said. In the current study, data from multiple hospitals allowed the researchers to examine differences in management across institutions, she said.

Dr. Rodriguez, with principal investigator Nicole Coufal, MD, also of Rady Children’s, and colleagues conducted the study at three children’s hospitals from March 2019 to July 2022. The study population included 80 children whose origin of illness was uncertain. The patients underwent rWGS testing in the PICU or cardiac ICU setting. The patients ranged in age from 0 to 17 years; 64% were younger than 1 year, (mean age, 2.8 years); 56% were male, and 59% were White.  

After rWGS testing, 65% of the children were positive for a genetic variant. The data prompted changes to care for 42% of these patients; 38% of the changes occurred during the patient’s PICU stay, including medication changes and procedures that were either avoided or completed.

The remaining 62% of the changes were subacute and affected management for the remainder of the child’s hospitalization and after discharge, Dr. Rodriguez explained in her presentation.

The average turnaround time for the testing was 10 days, which is important to an intensivist, who may have been hesitant to order tests because of the time involved, Dr. Rodriguez said. The current study shows that “we can get test results in a reasonable time to make meaningful changes in care,” she told this news organization.

Choosing which patients to test can be a challenge for clinicians, Dr. Rodriguez acknowledged. “We have gotten a sense of which patients are likely to have diagnostic or not diagnostic genomes, but it is also a gut feeling,” she said.

“If this child is your patient and you are concerned, if they seem sicker than expected, or have a concerning family history, then send the test,” she said. “It is becoming more affordable, and can come back quickly enough to guide treatment while the patient is still in the ICU.”

In the current study, the greatest diagnostic utility appeared in patients with cardiac symptoms, such as congenital heart disease, sudden cardiac arrest, or suspected channelopathy, Dr. Rodriguez said in her presentation.

Patients with suspected neurological disease had a 50% rate of molecular diagnosis. “Interestingly, 74% of patients with respiratory disease where an underlying genetic etiology was suspected received a molecular diagnosis,” although rWGS was not applied to general populations with RSV or other respiratory illnesses, she said.

In her presentation, Dr. Rodriguez shared examples of how genetic testing had a dramatic impact on patient survival. In one case, a 14-year-old girl presented in cardiac arrest and was found to have new-onset dilated cardiomyopathy. Whether the etiology was acquired or infectious and possibly reversible or genetic was unclear, she said.

“A diagnostic genome result within 48 hours indicated a genetic etiology,” she said. The patient was listed for heart transplant despite the incomplete infectious workup, and received a successful heart transplant 1 week after admission, Dr. Rodriguez said.

Guidelines for which PICU patients should undergo genetic testing do not yet exist, Dr. Rodriguez told this news organization. “We are trying to find some more meaningful parameters where we can say that a patient has a high pretest possibility of a genetic condition,” she said.

“Increasing availability of rWGS can significantly impact patient care and assist families in making difficult decisions during times of critical illness,” she said.

Insurance coverage and testing access are improving, said Dr. Rodriguez. Medicaid policies exist for neonates/infants in the ICU in several states, including Oregon, California, Michigan, Maryland, and Louisiana, she said. In some areas, hospitals may pay for testing for these children if insurance will not, she added.

Dr. Rodriguez and colleagues are continuing to enroll patients in a prospective study of the impact of rWGS, with the addition of a fourth study site and inclusion of family surveys. “We also will be looking at a secondary analysis of cost savings and benefits,” she said.

Ultimately, the current study should be empowering to physicians, “especially if they don’t have good access to geneticists,” Dr. Rodriguez said in an interview.

The study received no outside funding. Dr. Rodriguez reports no relevant financial relationships. 

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

Two-thirds of children who underwent genetic testing in the pediatric intensive care unit showed a genetic variant, and a third of these children received changes in care as a result, according to a new study presented at the Society of Critical Care Medicine’s 2023 Critical Care Congress.

“We have had a lot of success using genome sequencing to help not only with diagnosis, but also changes in management,” lead author Katherine Rodriguez, MD, a pediatric critical care fellow physician at Rady Children’s Hospital, San Diego, told this news organization.

However, data on the use of rapid whole genome sequencing (rWGS) in the pediatric intensive care unit (PICU) are limited, and data from multiple institutions are lacking, Dr. Rodriguez said. In the current study, data from multiple hospitals allowed the researchers to examine differences in management across institutions, she said.

Dr. Rodriguez, with principal investigator Nicole Coufal, MD, also of Rady Children’s, and colleagues conducted the study at three children’s hospitals from March 2019 to July 2022. The study population included 80 children whose origin of illness was uncertain. The patients underwent rWGS testing in the PICU or cardiac ICU setting. The patients ranged in age from 0 to 17 years; 64% were younger than 1 year, (mean age, 2.8 years); 56% were male, and 59% were White.  

After rWGS testing, 65% of the children were positive for a genetic variant. The data prompted changes to care for 42% of these patients; 38% of the changes occurred during the patient’s PICU stay, including medication changes and procedures that were either avoided or completed.

The remaining 62% of the changes were subacute and affected management for the remainder of the child’s hospitalization and after discharge, Dr. Rodriguez explained in her presentation.

The average turnaround time for the testing was 10 days, which is important to an intensivist, who may have been hesitant to order tests because of the time involved, Dr. Rodriguez said. The current study shows that “we can get test results in a reasonable time to make meaningful changes in care,” she told this news organization.

Choosing which patients to test can be a challenge for clinicians, Dr. Rodriguez acknowledged. “We have gotten a sense of which patients are likely to have diagnostic or not diagnostic genomes, but it is also a gut feeling,” she said.

“If this child is your patient and you are concerned, if they seem sicker than expected, or have a concerning family history, then send the test,” she said. “It is becoming more affordable, and can come back quickly enough to guide treatment while the patient is still in the ICU.”

In the current study, the greatest diagnostic utility appeared in patients with cardiac symptoms, such as congenital heart disease, sudden cardiac arrest, or suspected channelopathy, Dr. Rodriguez said in her presentation.

Patients with suspected neurological disease had a 50% rate of molecular diagnosis. “Interestingly, 74% of patients with respiratory disease where an underlying genetic etiology was suspected received a molecular diagnosis,” although rWGS was not applied to general populations with RSV or other respiratory illnesses, she said.

In her presentation, Dr. Rodriguez shared examples of how genetic testing had a dramatic impact on patient survival. In one case, a 14-year-old girl presented in cardiac arrest and was found to have new-onset dilated cardiomyopathy. Whether the etiology was acquired or infectious and possibly reversible or genetic was unclear, she said.

“A diagnostic genome result within 48 hours indicated a genetic etiology,” she said. The patient was listed for heart transplant despite the incomplete infectious workup, and received a successful heart transplant 1 week after admission, Dr. Rodriguez said.

Guidelines for which PICU patients should undergo genetic testing do not yet exist, Dr. Rodriguez told this news organization. “We are trying to find some more meaningful parameters where we can say that a patient has a high pretest possibility of a genetic condition,” she said.

“Increasing availability of rWGS can significantly impact patient care and assist families in making difficult decisions during times of critical illness,” she said.

Insurance coverage and testing access are improving, said Dr. Rodriguez. Medicaid policies exist for neonates/infants in the ICU in several states, including Oregon, California, Michigan, Maryland, and Louisiana, she said. In some areas, hospitals may pay for testing for these children if insurance will not, she added.

Dr. Rodriguez and colleagues are continuing to enroll patients in a prospective study of the impact of rWGS, with the addition of a fourth study site and inclusion of family surveys. “We also will be looking at a secondary analysis of cost savings and benefits,” she said.

Ultimately, the current study should be empowering to physicians, “especially if they don’t have good access to geneticists,” Dr. Rodriguez said in an interview.

The study received no outside funding. Dr. Rodriguez reports no relevant financial relationships. 

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

Two-thirds of children who underwent genetic testing in the pediatric intensive care unit showed a genetic variant, and a third of these children received changes in care as a result, according to a new study presented at the Society of Critical Care Medicine’s 2023 Critical Care Congress.

“We have had a lot of success using genome sequencing to help not only with diagnosis, but also changes in management,” lead author Katherine Rodriguez, MD, a pediatric critical care fellow physician at Rady Children’s Hospital, San Diego, told this news organization.

However, data on the use of rapid whole genome sequencing (rWGS) in the pediatric intensive care unit (PICU) are limited, and data from multiple institutions are lacking, Dr. Rodriguez said. In the current study, data from multiple hospitals allowed the researchers to examine differences in management across institutions, she said.

Dr. Rodriguez, with principal investigator Nicole Coufal, MD, also of Rady Children’s, and colleagues conducted the study at three children’s hospitals from March 2019 to July 2022. The study population included 80 children whose origin of illness was uncertain. The patients underwent rWGS testing in the PICU or cardiac ICU setting. The patients ranged in age from 0 to 17 years; 64% were younger than 1 year, (mean age, 2.8 years); 56% were male, and 59% were White.  

After rWGS testing, 65% of the children were positive for a genetic variant. The data prompted changes to care for 42% of these patients; 38% of the changes occurred during the patient’s PICU stay, including medication changes and procedures that were either avoided or completed.

The remaining 62% of the changes were subacute and affected management for the remainder of the child’s hospitalization and after discharge, Dr. Rodriguez explained in her presentation.

The average turnaround time for the testing was 10 days, which is important to an intensivist, who may have been hesitant to order tests because of the time involved, Dr. Rodriguez said. The current study shows that “we can get test results in a reasonable time to make meaningful changes in care,” she told this news organization.

Choosing which patients to test can be a challenge for clinicians, Dr. Rodriguez acknowledged. “We have gotten a sense of which patients are likely to have diagnostic or not diagnostic genomes, but it is also a gut feeling,” she said.

“If this child is your patient and you are concerned, if they seem sicker than expected, or have a concerning family history, then send the test,” she said. “It is becoming more affordable, and can come back quickly enough to guide treatment while the patient is still in the ICU.”

In the current study, the greatest diagnostic utility appeared in patients with cardiac symptoms, such as congenital heart disease, sudden cardiac arrest, or suspected channelopathy, Dr. Rodriguez said in her presentation.

Patients with suspected neurological disease had a 50% rate of molecular diagnosis. “Interestingly, 74% of patients with respiratory disease where an underlying genetic etiology was suspected received a molecular diagnosis,” although rWGS was not applied to general populations with RSV or other respiratory illnesses, she said.

In her presentation, Dr. Rodriguez shared examples of how genetic testing had a dramatic impact on patient survival. In one case, a 14-year-old girl presented in cardiac arrest and was found to have new-onset dilated cardiomyopathy. Whether the etiology was acquired or infectious and possibly reversible or genetic was unclear, she said.

“A diagnostic genome result within 48 hours indicated a genetic etiology,” she said. The patient was listed for heart transplant despite the incomplete infectious workup, and received a successful heart transplant 1 week after admission, Dr. Rodriguez said.

Guidelines for which PICU patients should undergo genetic testing do not yet exist, Dr. Rodriguez told this news organization. “We are trying to find some more meaningful parameters where we can say that a patient has a high pretest possibility of a genetic condition,” she said.

“Increasing availability of rWGS can significantly impact patient care and assist families in making difficult decisions during times of critical illness,” she said.

Insurance coverage and testing access are improving, said Dr. Rodriguez. Medicaid policies exist for neonates/infants in the ICU in several states, including Oregon, California, Michigan, Maryland, and Louisiana, she said. In some areas, hospitals may pay for testing for these children if insurance will not, she added.

Dr. Rodriguez and colleagues are continuing to enroll patients in a prospective study of the impact of rWGS, with the addition of a fourth study site and inclusion of family surveys. “We also will be looking at a secondary analysis of cost savings and benefits,” she said.

Ultimately, the current study should be empowering to physicians, “especially if they don’t have good access to geneticists,” Dr. Rodriguez said in an interview.

The study received no outside funding. Dr. Rodriguez reports no relevant financial relationships. 

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

Young adults who survive cancer are more likely than cancer-free siblings to be lonely and to develop emotional distress, risky behaviors, and new chronic conditions as a result, findings from a large retrospective study suggest.

Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.

“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”

The article was published online in the journal Cancer.

Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.

“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.

To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.

The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.

The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.

Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).

Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).

Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).

Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.

The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.

Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.

“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.

Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.

Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”

Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.

The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.

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

Young adults who survive cancer are more likely than cancer-free siblings to be lonely and to develop emotional distress, risky behaviors, and new chronic conditions as a result, findings from a large retrospective study suggest.

Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.

“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”

The article was published online in the journal Cancer.

Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.

“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.

To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.

The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.

The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.

Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).

Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).

Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).

Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.

The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.

Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.

“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.

Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.

Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”

Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.

The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.

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

Young adults who survive cancer are more likely than cancer-free siblings to be lonely and to develop emotional distress, risky behaviors, and new chronic conditions as a result, findings from a large retrospective study suggest.

Young cancer survivors were more than twice as likely to report loneliness at study baseline and follow-up. Loneliness at these times was associated with an almost 10-fold increased risk for anxiety and a nearly 18-fold increased risk for depression.

“We observed an elevated prevalence of loneliness in survivors, compared to sibling controls, and found that loneliness was associated with emotional, behavioral, and physical health morbidities,” lead study author Chiara Papini, PhD, of St. Jude Children’s Research Hospital, Memphis, and her colleagues write. “Our results highlight the importance of identifying and screening young adult survivors of childhood cancer for loneliness and the need for targeted interventions to reduce loneliness.”

The article was published online in the journal Cancer.

Most young cancer survivors in the United States reach adulthood and need to play catch-up: make up for missed school and work, become reacquainted with old friends, and develop new friendships, social networks, and intimate relationships. Meeting these needs may be hindered by adverse physical and psychosocial problems that linger or develop after treatment, which may leave cancer survivors feeling isolated.

“Young adult survivors of childhood cancer are navigating a developmental period marked by increased social expectations, during which loneliness may have significant impact on physical and mental health,” Dr. Papini and colleagues say.

To better understand the risks for loneliness among young cancer survivors, Dr. Papini and her colleagues analyzed data from the retrospective Childhood Cancer Survivor Study, which followed young survivors who had been diagnosed with a range of cancers before age 21 years. Study participants had been treated at one of 31 study sites in North America and had survived 5 years or longer after diagnosis.

The 9,664 survivors and 2,221 randomly sampled siblings ranged in age from 19 to 39 years at the time they completed a survey that assessed emotional distress at baseline and at follow‐up a median of 6.6 years. At baseline, the median age of the survivors was 27 years, and a median of 17.5 years had passed from the time of their diagnosis.

The most common diagnoses were leukemia (35%), Hodgkin lymphoma (15%), central nervous system (CNS) tumors (14%), and bone tumors (10%). More than half (56%) had received radiation therapy.

Using multivariable models, the researchers found that survivors were more likely than siblings to report moderate to extreme loneliness at either baseline or follow‐up (prevalence ratio, 1.04) and were more than two times more likely to report loneliness at both baseline and follow‐up (PR, 2.21).

Loneliness at baseline and follow‐up was associated with a much greater risk for anxiety (relative risk, 9.75) and depression (RR, 17.86). Loneliness at follow‐up was linked with increased risks for suicidal ideation (RR, 1.52), heavy or risky alcohol consumption (RR, 1.27), and any grade 2-4 new‐onset chronic health condition (RR, 1.29), especially those that were neurologic (RR, 4.37).

Survivors of CNS tumors (odds ratio, 2.59) and leukemia (OR, 2.52) were most likely to report loneliness at both baseline and follow‐up, though survivors of four other cancer types also faced an elevated risk for loneliness: neuroblastoma (OR, 2.32), bone tumor (OR, 2.12), soft tissue sarcoma (OR, 1.78), and Hodgkin lymphoma (OR, 1.69).

Treatment type appeared to matter as well. Survivors who underwent amputation (OR, 1.82) or were treated with cranial radiation greater than or equal to 20 Gy (OR, 1.56) or corticosteroids (OR, 1.31) were more likely to report loneliness at baseline and follow‐up, compared with those who reported no loneliness at both time points.

The authors acknowledge limitations to the study, including the fact that roughly 90% of survivors and siblings were White, which limits the applicability of their results to diverse groups. In addition, the responses were self-reported without external validation.

Overall, though, the findings provide a framework for clinicians to understand and identify loneliness among young cancer survivors and help them cope with their emotions.

“The Childhood Cancer Survivor Study provides the largest and the most comprehensive dataset on childhood cancer survivors and healthy-sibling comparisons, giving us powerful data on survivorship, late effects, and psychosocial and health outcomes,” Rachel M. Moore, PhD, child psychologist at Children’s Mercy Kansas City, Mo., said in an interview.

Asking a simple question – “Are you feeling lonely?” – can identify at-risk survivors and enable health care teams to provide timely interventions that address young patients’ physical and psychological needs, said Dr. Moore, who was not involved in the study.

Dr. Moore noted that within her clinical practice, “adolescent and young adult survivors frequently discuss loneliness in their daily lives. They feel different from their peers and misunderstood. Having a conversation early in survivorship care about the experience of loneliness as a product of cancer treatment can open the door to regular screening and destigmatizing mental health services.”

Supporting young people throughout their survivorship journey is important, said Rusha Bhandari, MD, medical director of the Childhood, Adolescent, and Young Adult Cancer Survivorship Program at City of Hope, Duarte, Calif. This study can help ensure that clinicians “provide comprehensive care, including psychosocial screening and support, to meet the unique needs of our young adult survivors,” said Dr. Bhandari, who also was not involved in the research.

The National Cancer Institute and the American Lebanese Syrian Associated Charities supported the study. One co-author reported receiving corporate consulting fees. Dr. Papini, the remaining co-authors, Dr. Moore, and Dr. Bhandari report no relevant financial involvements.

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