Digestive Disease Week^® (DDW) is taking place May 2-5, 2020, at McCormick Place in Chicago, Ill. Featuring clinical care updates – presented nowhere else during DDW – the AGA Postgraduate Course will be held in conjunction with DDW on May 2 and 3. You can register for both together. Visit DDW.org and AGA University, agau.gastro.org, to learn more about each.

Improve patient care

The AGA Postgraduate Course is a comprehensive 1.5-day program highlighting ground-breaking advances in the delivery of high-quality, patient-centered GI care. Attendees will participate in dynamic case-based sessions, learning lunches and panel discussions, and will walk away with best practices for treating a variety of disease states and digestive disorders.
 

The brightest ideas and breakthroughs in digestive disease

DDW continues to improve and consolidate its reputation as the meeting that brings the brightest ideas and breakthroughs in digestive disease. Prepare to be blown away in the Windy City by all that DDW has to offer:

More than 400 scientific sessions, organized by educational tracks and presented in a wide range of session formats. New sessions include an AGA Clinical Plenary, Topic-Focused Workshops on hypnosis techniques and nutrition, and expanded programming in the DDW Trainee and Early Career Lounge.

Opportunities to connect with over 14,000 attendees from around the world, including top GI experts. New Continuing Conversation blocks, immediately following select invited-speaker sessions, allow you time to network with presenters and fellow attendees.

An Exhibit Hall spotlighting new innovations and technologies that you can implement in your practice.

Digestive Disease Week^® (DDW) is taking place May 2-5, 2020, at McCormick Place in Chicago, Ill. Featuring clinical care updates – presented nowhere else during DDW – the AGA Postgraduate Course will be held in conjunction with DDW on May 2 and 3. You can register for both together. Visit DDW.org and AGA University, agau.gastro.org, to learn more about each.

Improve patient care

The AGA Postgraduate Course is a comprehensive 1.5-day program highlighting ground-breaking advances in the delivery of high-quality, patient-centered GI care. Attendees will participate in dynamic case-based sessions, learning lunches and panel discussions, and will walk away with best practices for treating a variety of disease states and digestive disorders.
 

The brightest ideas and breakthroughs in digestive disease

DDW continues to improve and consolidate its reputation as the meeting that brings the brightest ideas and breakthroughs in digestive disease. Prepare to be blown away in the Windy City by all that DDW has to offer:

More than 400 scientific sessions, organized by educational tracks and presented in a wide range of session formats. New sessions include an AGA Clinical Plenary, Topic-Focused Workshops on hypnosis techniques and nutrition, and expanded programming in the DDW Trainee and Early Career Lounge.

Opportunities to connect with over 14,000 attendees from around the world, including top GI experts. New Continuing Conversation blocks, immediately following select invited-speaker sessions, allow you time to network with presenters and fellow attendees.

An Exhibit Hall spotlighting new innovations and technologies that you can implement in your practice.

Digestive Disease Week^® (DDW) is taking place May 2-5, 2020, at McCormick Place in Chicago, Ill. Featuring clinical care updates – presented nowhere else during DDW – the AGA Postgraduate Course will be held in conjunction with DDW on May 2 and 3. You can register for both together. Visit DDW.org and AGA University, agau.gastro.org, to learn more about each.

Improve patient care

The AGA Postgraduate Course is a comprehensive 1.5-day program highlighting ground-breaking advances in the delivery of high-quality, patient-centered GI care. Attendees will participate in dynamic case-based sessions, learning lunches and panel discussions, and will walk away with best practices for treating a variety of disease states and digestive disorders.
 

The brightest ideas and breakthroughs in digestive disease

DDW continues to improve and consolidate its reputation as the meeting that brings the brightest ideas and breakthroughs in digestive disease. Prepare to be blown away in the Windy City by all that DDW has to offer:

More than 400 scientific sessions, organized by educational tracks and presented in a wide range of session formats. New sessions include an AGA Clinical Plenary, Topic-Focused Workshops on hypnosis techniques and nutrition, and expanded programming in the DDW Trainee and Early Career Lounge.

Opportunities to connect with over 14,000 attendees from around the world, including top GI experts. New Continuing Conversation blocks, immediately following select invited-speaker sessions, allow you time to network with presenters and fellow attendees.

An Exhibit Hall spotlighting new innovations and technologies that you can implement in your practice.

We’re celebrating diversity in our field with a new series spotlighting members of the AGA Diversity Committee and AGA FORWARD Program.

Born and raised in Cuba, Mayra Sanchez, MD, came to this country as an adult, with little money in her pocket and no recognition of her previous medical training. Unfortunately, she explains, her story is not uncommon.

“I first got involved with the AGA Diversity Committee to ensure there is recognition of those who come to our field from nontraditional paths such as this.”

Her professional hero is Dr. Guadalupe Garcia-Tsao, a senior hepatologist at Yale.

“She is inspiring as an engaging teacher and as a role model for practicing cutting-edge medicine, but she also is my hero because she was able to rise to a leadership position despite the challenges of being a minority.”

An issue affecting underrepresented minorities at the top of her radar is the need for more mentorship.

While serving on the committee, she also wants to stimulate a deeper understanding among colleagues of the value people bring by virtue of their different backgrounds, both in the gastroenterology and hepatology fields, and in GI patients.

“The practice of gastroenterology allows me to understand mind-body interactions and to appreciate how each person’s life experiences and emotional well-being contributes to her or his digestive health.”
 

Let’s get personal

What are you most proud of in your career? “I am proud that I built a very large, very busy, state-of-the-art motility practice at Yale University. Despite the fact that we have one of the biggest motility practices on the East Coast, we also pride ourselves on our dedication to patient care and patient satisfaction.”

... In your personal life? “In my personal life, I am proud to have two beautiful children and a wonderful husband who serve as constant reminders of the importance of life outside of the workplace.”

What’s your favorite part of your job? “Making a difference in people’s lives, especially when others have not been able to.”

What do you know now that you wish someone told you when you started your career? “The importance of persistence cannot be overstated.”

If I weren’t in gastroenterology, I would be ... “a writer.”

In my free time I like to ... “travel with my family to experience new cultures.”

We’re celebrating diversity in our field with a new series spotlighting members of the AGA Diversity Committee and AGA FORWARD Program.

Born and raised in Cuba, Mayra Sanchez, MD, came to this country as an adult, with little money in her pocket and no recognition of her previous medical training. Unfortunately, she explains, her story is not uncommon.

“I first got involved with the AGA Diversity Committee to ensure there is recognition of those who come to our field from nontraditional paths such as this.”

Her professional hero is Dr. Guadalupe Garcia-Tsao, a senior hepatologist at Yale.

“She is inspiring as an engaging teacher and as a role model for practicing cutting-edge medicine, but she also is my hero because she was able to rise to a leadership position despite the challenges of being a minority.”

An issue affecting underrepresented minorities at the top of her radar is the need for more mentorship.

While serving on the committee, she also wants to stimulate a deeper understanding among colleagues of the value people bring by virtue of their different backgrounds, both in the gastroenterology and hepatology fields, and in GI patients.

“The practice of gastroenterology allows me to understand mind-body interactions and to appreciate how each person’s life experiences and emotional well-being contributes to her or his digestive health.”
 

Let’s get personal

What are you most proud of in your career? “I am proud that I built a very large, very busy, state-of-the-art motility practice at Yale University. Despite the fact that we have one of the biggest motility practices on the East Coast, we also pride ourselves on our dedication to patient care and patient satisfaction.”

... In your personal life? “In my personal life, I am proud to have two beautiful children and a wonderful husband who serve as constant reminders of the importance of life outside of the workplace.”

What’s your favorite part of your job? “Making a difference in people’s lives, especially when others have not been able to.”

What do you know now that you wish someone told you when you started your career? “The importance of persistence cannot be overstated.”

If I weren’t in gastroenterology, I would be ... “a writer.”

In my free time I like to ... “travel with my family to experience new cultures.”

We’re celebrating diversity in our field with a new series spotlighting members of the AGA Diversity Committee and AGA FORWARD Program.

Born and raised in Cuba, Mayra Sanchez, MD, came to this country as an adult, with little money in her pocket and no recognition of her previous medical training. Unfortunately, she explains, her story is not uncommon.

“I first got involved with the AGA Diversity Committee to ensure there is recognition of those who come to our field from nontraditional paths such as this.”

Her professional hero is Dr. Guadalupe Garcia-Tsao, a senior hepatologist at Yale.

“She is inspiring as an engaging teacher and as a role model for practicing cutting-edge medicine, but she also is my hero because she was able to rise to a leadership position despite the challenges of being a minority.”

An issue affecting underrepresented minorities at the top of her radar is the need for more mentorship.

While serving on the committee, she also wants to stimulate a deeper understanding among colleagues of the value people bring by virtue of their different backgrounds, both in the gastroenterology and hepatology fields, and in GI patients.

“The practice of gastroenterology allows me to understand mind-body interactions and to appreciate how each person’s life experiences and emotional well-being contributes to her or his digestive health.”
 

Let’s get personal

What are you most proud of in your career? “I am proud that I built a very large, very busy, state-of-the-art motility practice at Yale University. Despite the fact that we have one of the biggest motility practices on the East Coast, we also pride ourselves on our dedication to patient care and patient satisfaction.”

... In your personal life? “In my personal life, I am proud to have two beautiful children and a wonderful husband who serve as constant reminders of the importance of life outside of the workplace.”

What’s your favorite part of your job? “Making a difference in people’s lives, especially when others have not been able to.”

What do you know now that you wish someone told you when you started your career? “The importance of persistence cannot be overstated.”

If I weren’t in gastroenterology, I would be ... “a writer.”

In my free time I like to ... “travel with my family to experience new cultures.”

Long-term AGA congressional champion and fierce physician-community advocate Congressman Phil Roe (R, Tenn), announced that he will not seek reelection in the upcoming 2020 election. Following his retirement announcement, Congressman Roe communicated to AGA and fellow health care organizations that he is still committed to ensuring the success of the prior authorization bill, H.R. 3107, before leaving Congress.

Congressman Roe, who was first elected to Congress in 2008 and is currently serving his sixth term, is an ob.gyn. by trade who practiced for 30 years before running for office. He originally ran for Congress on a platform touting his experience as a practicing physician to drive and positively impact health care policy. Upon entering Congress, he did just that – focusing his legislative attention and efforts on policies that protect patients, ease administrative burdens, and protect fair reimbursements for specialty physicians. Throughout his tenure, Congressman Roe served both his constituents and his colleagues in the House of Representatives as a valued and respected leader on health care issues. He currently serves as the top-ranking Republican on the Veteran’s Affairs Committee and as co-chair of both the House Doctor’s Caucus and the Congressional Academic Medicine Caucus. His primary focus as a member of Congress has always been on health care issues – many of which include AGA’s top policy priorities.
 

GI wins with Roe

Sustainable Growth Rate (SGR). Congressman Roe was an instrumental figure in the bipartisan victory to repeal the flawed Medicare physician payment formula, known as SGR, in 2015. Throughout the deliberation of SGR repeal legislation, he stayed in close contact with physician groups and actively whipped House members for support.

Independent Payment Advisory Board (IPAB). Congressman Roe was a key ally in the fight to repeal the IPAB, which was created under the Affordable Care Act and which AGA and all of organized medicine long opposed since its sole purpose was to make budgetary cuts to Medicare if it reached a certain threshold of spending. Largely because of Congressman Roe’s leadership on this issue, the IPAB was successfully repealed after years of advocacy on the issue.

Through AGA PAC, AGA staff was afforded the opportunity to cultivate a strong working relationship over the years with Congressman Roe and his staff. While his leadership and commitment to pro-patient, pro-physician policies will be missed following his retirement from Congress, AGA staff looks forward to working with Congressman Roe through the remainder of his term on issues that impact our patients and our practice.

Long-term AGA congressional champion and fierce physician-community advocate Congressman Phil Roe (R, Tenn), announced that he will not seek reelection in the upcoming 2020 election. Following his retirement announcement, Congressman Roe communicated to AGA and fellow health care organizations that he is still committed to ensuring the success of the prior authorization bill, H.R. 3107, before leaving Congress.

Congressman Roe, who was first elected to Congress in 2008 and is currently serving his sixth term, is an ob.gyn. by trade who practiced for 30 years before running for office. He originally ran for Congress on a platform touting his experience as a practicing physician to drive and positively impact health care policy. Upon entering Congress, he did just that – focusing his legislative attention and efforts on policies that protect patients, ease administrative burdens, and protect fair reimbursements for specialty physicians. Throughout his tenure, Congressman Roe served both his constituents and his colleagues in the House of Representatives as a valued and respected leader on health care issues. He currently serves as the top-ranking Republican on the Veteran’s Affairs Committee and as co-chair of both the House Doctor’s Caucus and the Congressional Academic Medicine Caucus. His primary focus as a member of Congress has always been on health care issues – many of which include AGA’s top policy priorities.
 

GI wins with Roe

Sustainable Growth Rate (SGR). Congressman Roe was an instrumental figure in the bipartisan victory to repeal the flawed Medicare physician payment formula, known as SGR, in 2015. Throughout the deliberation of SGR repeal legislation, he stayed in close contact with physician groups and actively whipped House members for support.

Independent Payment Advisory Board (IPAB). Congressman Roe was a key ally in the fight to repeal the IPAB, which was created under the Affordable Care Act and which AGA and all of organized medicine long opposed since its sole purpose was to make budgetary cuts to Medicare if it reached a certain threshold of spending. Largely because of Congressman Roe’s leadership on this issue, the IPAB was successfully repealed after years of advocacy on the issue.

Through AGA PAC, AGA staff was afforded the opportunity to cultivate a strong working relationship over the years with Congressman Roe and his staff. While his leadership and commitment to pro-patient, pro-physician policies will be missed following his retirement from Congress, AGA staff looks forward to working with Congressman Roe through the remainder of his term on issues that impact our patients and our practice.

Long-term AGA congressional champion and fierce physician-community advocate Congressman Phil Roe (R, Tenn), announced that he will not seek reelection in the upcoming 2020 election. Following his retirement announcement, Congressman Roe communicated to AGA and fellow health care organizations that he is still committed to ensuring the success of the prior authorization bill, H.R. 3107, before leaving Congress.

Congressman Roe, who was first elected to Congress in 2008 and is currently serving his sixth term, is an ob.gyn. by trade who practiced for 30 years before running for office. He originally ran for Congress on a platform touting his experience as a practicing physician to drive and positively impact health care policy. Upon entering Congress, he did just that – focusing his legislative attention and efforts on policies that protect patients, ease administrative burdens, and protect fair reimbursements for specialty physicians. Throughout his tenure, Congressman Roe served both his constituents and his colleagues in the House of Representatives as a valued and respected leader on health care issues. He currently serves as the top-ranking Republican on the Veteran’s Affairs Committee and as co-chair of both the House Doctor’s Caucus and the Congressional Academic Medicine Caucus. His primary focus as a member of Congress has always been on health care issues – many of which include AGA’s top policy priorities.
 

GI wins with Roe

Sustainable Growth Rate (SGR). Congressman Roe was an instrumental figure in the bipartisan victory to repeal the flawed Medicare physician payment formula, known as SGR, in 2015. Throughout the deliberation of SGR repeal legislation, he stayed in close contact with physician groups and actively whipped House members for support.

Independent Payment Advisory Board (IPAB). Congressman Roe was a key ally in the fight to repeal the IPAB, which was created under the Affordable Care Act and which AGA and all of organized medicine long opposed since its sole purpose was to make budgetary cuts to Medicare if it reached a certain threshold of spending. Largely because of Congressman Roe’s leadership on this issue, the IPAB was successfully repealed after years of advocacy on the issue.

Through AGA PAC, AGA staff was afforded the opportunity to cultivate a strong working relationship over the years with Congressman Roe and his staff. While his leadership and commitment to pro-patient, pro-physician policies will be missed following his retirement from Congress, AGA staff looks forward to working with Congressman Roe through the remainder of his term on issues that impact our patients and our practice.

LOS ANGELES – A new potential neuroprotectant agent has been found to be beneficial for patients with acute ischemic stroke undergoing endovascular thrombectomy in a large placebo-controlled trial, but only for those patients who did not also receive thrombolysis.
 

There was no difference between groups on the primary outcome in the main analysis of the trial, lead author Michael Hill, MD, reported.

However, “In our study, we found a dramatic interaction of nerinetide with alteplase. There was a large benefit of nerinetide in patients not given thrombolysis, but in patients who received alteplase, this benefit was completely obliterated,” Dr. Hill said in an interview.

“In patients not treated with thrombolysis, we found a large effect size with a 9.5% absolute improvement in patients having an independent outcome (modified Rankin Score [mRS] 0-2) and a number need to treat of 10 to 11,” he said. “We also found a mortality benefit and a reduction in the size of strokes, with all other secondary outcomes going in the right direction.

“The drug works really well in patients who do not get thrombolysis, but it doesn’t work at all in patients who have had thrombolysis. The thrombolytic appears to break the peptide down so it is inactive,” he added.

“This is the first evidence that neuroprotection is possible in human stroke. This has never been shown before,” Dr. Hill noted. “Many previous clinical trials of potential neuroprotectants have been negative. We think this is a major breakthrough. This is pretty exciting stuff with really tantalizing results.”

Dr. Hill, professor of neurology at the University of Calgary (Alta.), presented results of the ESCAPE-NA1 trial on Feb. 20 at the International Stroke Conference (ISC) 2020. The trial was also simultaneously published online (Lancet. 2020 Feb 20; doi: 10.1016/S0140-6736(20)30258-0).

Endogenous nitric oxide

The new agent – known as NA1 or nerinetide – is a 20-amino-acid peptide with a novel mechanism of action; it inhibits signaling that leads to neuronal excitotoxicity. “It reduces endogenous nitric oxide generated inside the cell during ischemia, which is one of the main biochemical processes contributing to cell death,” Dr. Hill explained. In a primate model of ischemia reperfusion that was published in Nature in 2012, it was highly protective, he added.

The drug is given just once at the time of thrombectomy. It is short lived in the blood but detectable in the brain for up to 24 hours, he said.

The trial included 1,105 patients who had experienced acute ischemic stroke due to large-vessel occlusion within a 12-hour treatment window and for whom imaging results suitable for thrombectomy were available. The patients were randomly assigned to receive either intravenous nerinetide in a single dose of 2.6 mg/kg or saline placebo at the time of thrombectomy.

Patients were stratified by intravenous alteplase treatment and by declared endovascular device choice.

“Shaking up the field”

There is still more work to do, Dr. Hill said. “We don’t fully understand the pharmacology, and we will certainly have to do another trial, but we believe this agent is going to shake the field up. This is a totally new drug, and we have to think carefully about where it could fit in.”

“The obvious first group is those patients who do not receive thrombolysis. This is a large group, as most patients do not present in time for thrombolysis. Then we can work on the biochemistry and see if we can develop a version of nerinetide that is resistant to breakdown by thrombolysis,” he said.

Another possibility would be to withhold thrombolysis and give nerinetide instead. “It may be that thrombolysis is not needed if patients are receiving thrombectomy – this is being suggested now in initial studies,” Hill stated.

They also chose a very select group of patients – those undergoing thrombectomy, who represent only 10% to 15% of stroke patients. “We have to work out how to expand that population,” he said.

Hill noted that there have been many examples in the past of potential neuroprotectant agents that have worked in animal models of ischemia-reperfusion but that failed in humans with acute stroke.

“Until recently, we have not had a reliable ischemia-reperfusion model in humans, but now with endovascular therapy, we have a situation where the blood flow is reliably restored, which is an ideal situation to test new neuroprotectant agents. That may be another factor that has contributed to our positive findings,” he said.

In an accompanying comment in The Lancet, Graeme J. Hankey, MD, of the University of Western Australia, Perth, noted that although endovascular thrombectomy after use of intravenous alteplase improves reperfusion and clinical outcomes for a fifth of patients with ischemic stroke caused by large-artery occlusion, half of patients do not recover an independent lifestyle. Cytoprotection aims to augment the resilience of neurons, neurovascular units, and white matter during ischemia until perfusion is restored (Lancet. 2020 Feb 20; doi: 10.1016/S0140-6736(20)30316-0).

Dr. Hankey also pointed out that numerous cytoprotection strategies have been reported to reduce brain infarction in preclinical models of ischemic stroke but have not been found to improve clinical outcomes in clinical trials involving patients with ischemic stroke.

The advent of thrombectomy provides an opportunity to reassess cytoprotection as an adjunctive therapy for patients with types of temporary brain ischemia that align more closely with successful preclinical models of ischemia, cytoprotection, and reperfusion, he added.

This article first appeared on Medscape.com.

LOS ANGELES – A new potential neuroprotectant agent has been found to be beneficial for patients with acute ischemic stroke undergoing endovascular thrombectomy in a large placebo-controlled trial, but only for those patients who did not also receive thrombolysis.
 

There was no difference between groups on the primary outcome in the main analysis of the trial, lead author Michael Hill, MD, reported.

However, “In our study, we found a dramatic interaction of nerinetide with alteplase. There was a large benefit of nerinetide in patients not given thrombolysis, but in patients who received alteplase, this benefit was completely obliterated,” Dr. Hill said in an interview.

“In patients not treated with thrombolysis, we found a large effect size with a 9.5% absolute improvement in patients having an independent outcome (modified Rankin Score [mRS] 0-2) and a number need to treat of 10 to 11,” he said. “We also found a mortality benefit and a reduction in the size of strokes, with all other secondary outcomes going in the right direction.

“The drug works really well in patients who do not get thrombolysis, but it doesn’t work at all in patients who have had thrombolysis. The thrombolytic appears to break the peptide down so it is inactive,” he added.

“This is the first evidence that neuroprotection is possible in human stroke. This has never been shown before,” Dr. Hill noted. “Many previous clinical trials of potential neuroprotectants have been negative. We think this is a major breakthrough. This is pretty exciting stuff with really tantalizing results.”

Dr. Hill, professor of neurology at the University of Calgary (Alta.), presented results of the ESCAPE-NA1 trial on Feb. 20 at the International Stroke Conference (ISC) 2020. The trial was also simultaneously published online (Lancet. 2020 Feb 20; doi: 10.1016/S0140-6736(20)30258-0).

Endogenous nitric oxide

The new agent – known as NA1 or nerinetide – is a 20-amino-acid peptide with a novel mechanism of action; it inhibits signaling that leads to neuronal excitotoxicity. “It reduces endogenous nitric oxide generated inside the cell during ischemia, which is one of the main biochemical processes contributing to cell death,” Dr. Hill explained. In a primate model of ischemia reperfusion that was published in Nature in 2012, it was highly protective, he added.

The drug is given just once at the time of thrombectomy. It is short lived in the blood but detectable in the brain for up to 24 hours, he said.

The trial included 1,105 patients who had experienced acute ischemic stroke due to large-vessel occlusion within a 12-hour treatment window and for whom imaging results suitable for thrombectomy were available. The patients were randomly assigned to receive either intravenous nerinetide in a single dose of 2.6 mg/kg or saline placebo at the time of thrombectomy.

Patients were stratified by intravenous alteplase treatment and by declared endovascular device choice.

“Shaking up the field”

There is still more work to do, Dr. Hill said. “We don’t fully understand the pharmacology, and we will certainly have to do another trial, but we believe this agent is going to shake the field up. This is a totally new drug, and we have to think carefully about where it could fit in.”

“The obvious first group is those patients who do not receive thrombolysis. This is a large group, as most patients do not present in time for thrombolysis. Then we can work on the biochemistry and see if we can develop a version of nerinetide that is resistant to breakdown by thrombolysis,” he said.

Another possibility would be to withhold thrombolysis and give nerinetide instead. “It may be that thrombolysis is not needed if patients are receiving thrombectomy – this is being suggested now in initial studies,” Hill stated.

They also chose a very select group of patients – those undergoing thrombectomy, who represent only 10% to 15% of stroke patients. “We have to work out how to expand that population,” he said.

Hill noted that there have been many examples in the past of potential neuroprotectant agents that have worked in animal models of ischemia-reperfusion but that failed in humans with acute stroke.

“Until recently, we have not had a reliable ischemia-reperfusion model in humans, but now with endovascular therapy, we have a situation where the blood flow is reliably restored, which is an ideal situation to test new neuroprotectant agents. That may be another factor that has contributed to our positive findings,” he said.

In an accompanying comment in The Lancet, Graeme J. Hankey, MD, of the University of Western Australia, Perth, noted that although endovascular thrombectomy after use of intravenous alteplase improves reperfusion and clinical outcomes for a fifth of patients with ischemic stroke caused by large-artery occlusion, half of patients do not recover an independent lifestyle. Cytoprotection aims to augment the resilience of neurons, neurovascular units, and white matter during ischemia until perfusion is restored (Lancet. 2020 Feb 20; doi: 10.1016/S0140-6736(20)30316-0).

Dr. Hankey also pointed out that numerous cytoprotection strategies have been reported to reduce brain infarction in preclinical models of ischemic stroke but have not been found to improve clinical outcomes in clinical trials involving patients with ischemic stroke.

The advent of thrombectomy provides an opportunity to reassess cytoprotection as an adjunctive therapy for patients with types of temporary brain ischemia that align more closely with successful preclinical models of ischemia, cytoprotection, and reperfusion, he added.

This article first appeared on Medscape.com.

LOS ANGELES – A new potential neuroprotectant agent has been found to be beneficial for patients with acute ischemic stroke undergoing endovascular thrombectomy in a large placebo-controlled trial, but only for those patients who did not also receive thrombolysis.
 

There was no difference between groups on the primary outcome in the main analysis of the trial, lead author Michael Hill, MD, reported.

However, “In our study, we found a dramatic interaction of nerinetide with alteplase. There was a large benefit of nerinetide in patients not given thrombolysis, but in patients who received alteplase, this benefit was completely obliterated,” Dr. Hill said in an interview.

“In patients not treated with thrombolysis, we found a large effect size with a 9.5% absolute improvement in patients having an independent outcome (modified Rankin Score [mRS] 0-2) and a number need to treat of 10 to 11,” he said. “We also found a mortality benefit and a reduction in the size of strokes, with all other secondary outcomes going in the right direction.

“The drug works really well in patients who do not get thrombolysis, but it doesn’t work at all in patients who have had thrombolysis. The thrombolytic appears to break the peptide down so it is inactive,” he added.

“This is the first evidence that neuroprotection is possible in human stroke. This has never been shown before,” Dr. Hill noted. “Many previous clinical trials of potential neuroprotectants have been negative. We think this is a major breakthrough. This is pretty exciting stuff with really tantalizing results.”

Dr. Hill, professor of neurology at the University of Calgary (Alta.), presented results of the ESCAPE-NA1 trial on Feb. 20 at the International Stroke Conference (ISC) 2020. The trial was also simultaneously published online (Lancet. 2020 Feb 20; doi: 10.1016/S0140-6736(20)30258-0).

Endogenous nitric oxide

The new agent – known as NA1 or nerinetide – is a 20-amino-acid peptide with a novel mechanism of action; it inhibits signaling that leads to neuronal excitotoxicity. “It reduces endogenous nitric oxide generated inside the cell during ischemia, which is one of the main biochemical processes contributing to cell death,” Dr. Hill explained. In a primate model of ischemia reperfusion that was published in Nature in 2012, it was highly protective, he added.

The drug is given just once at the time of thrombectomy. It is short lived in the blood but detectable in the brain for up to 24 hours, he said.

The trial included 1,105 patients who had experienced acute ischemic stroke due to large-vessel occlusion within a 12-hour treatment window and for whom imaging results suitable for thrombectomy were available. The patients were randomly assigned to receive either intravenous nerinetide in a single dose of 2.6 mg/kg or saline placebo at the time of thrombectomy.

Patients were stratified by intravenous alteplase treatment and by declared endovascular device choice.

“Shaking up the field”

There is still more work to do, Dr. Hill said. “We don’t fully understand the pharmacology, and we will certainly have to do another trial, but we believe this agent is going to shake the field up. This is a totally new drug, and we have to think carefully about where it could fit in.”

“The obvious first group is those patients who do not receive thrombolysis. This is a large group, as most patients do not present in time for thrombolysis. Then we can work on the biochemistry and see if we can develop a version of nerinetide that is resistant to breakdown by thrombolysis,” he said.

Another possibility would be to withhold thrombolysis and give nerinetide instead. “It may be that thrombolysis is not needed if patients are receiving thrombectomy – this is being suggested now in initial studies,” Hill stated.

They also chose a very select group of patients – those undergoing thrombectomy, who represent only 10% to 15% of stroke patients. “We have to work out how to expand that population,” he said.

Hill noted that there have been many examples in the past of potential neuroprotectant agents that have worked in animal models of ischemia-reperfusion but that failed in humans with acute stroke.

“Until recently, we have not had a reliable ischemia-reperfusion model in humans, but now with endovascular therapy, we have a situation where the blood flow is reliably restored, which is an ideal situation to test new neuroprotectant agents. That may be another factor that has contributed to our positive findings,” he said.

In an accompanying comment in The Lancet, Graeme J. Hankey, MD, of the University of Western Australia, Perth, noted that although endovascular thrombectomy after use of intravenous alteplase improves reperfusion and clinical outcomes for a fifth of patients with ischemic stroke caused by large-artery occlusion, half of patients do not recover an independent lifestyle. Cytoprotection aims to augment the resilience of neurons, neurovascular units, and white matter during ischemia until perfusion is restored (Lancet. 2020 Feb 20; doi: 10.1016/S0140-6736(20)30316-0).

Dr. Hankey also pointed out that numerous cytoprotection strategies have been reported to reduce brain infarction in preclinical models of ischemic stroke but have not been found to improve clinical outcomes in clinical trials involving patients with ischemic stroke.

The advent of thrombectomy provides an opportunity to reassess cytoprotection as an adjunctive therapy for patients with types of temporary brain ischemia that align more closely with successful preclinical models of ischemia, cytoprotection, and reperfusion, he added.

This article first appeared on Medscape.com.

Severe infection is linked to an increased risk of substance-induced psychosis and subsequent conversion to schizophrenia, new research suggests.

Results of the large, population-based study showed any infection was associated with a 30% increased risk for substance-induced psychosis. However, with more than a threefold increased risk for substance-induced psychosis, hepatitis was the infection most strongly linked to psychosis and the only infection associated with conversion to schizophrenia.

“Severe infections are associated with an increased risk of developing a substance-induced psychosis. Furthermore, hepatitis following substance-induced psychosis is associated with an increase in the risk of conversion to schizophrenia. Both of these observations support the hypothesis of an immunological component to psychosis,” wrote the investigators, led by Carsten Hjorthøj, PhD, MSc, Copenhagen Research Center for Mental Health, Denmark.

The study was published online Feb. 12 in the American Journal of Psychiatry. 

Mechanism still poorly understood

Previous research suggests that infection increases the risk for schizophrenia, but this new study is the first to investigate the association between infection and substance-induced psychosis.

Using Danish national registry data, the researchers analyzed data on all individuals born in Denmark since 1981. Of the 2,256,779 people, the researchers identified 3,618 cases of incident substance-induced psychosis.

Any infection increased the risk for substance-induced psychosis in the fully-adjusted model (hazard ratio = 1.30; 95% confidence interval, 1.22–1.39; P less than .001). The risk was doubled in the first 2 years following a severe infection and stayed elevated for more than 20 years. 

Hepatitis was the infection most strongly associated with substance-induced psychosis (HR = 3.42; 95% CI, 2.47–4.74; P less than .001) and only hepatitis predicted conversion to schizophrenia after substance-induced psychosis (HR = 1.87; 95% CI, 1.07–3.26; P = .03).

These results, the investigators note, “mirror previous findings on the association between infections and schizophrenia, including previous observations that the link is particularly strong for hepatitis.”

They also point out that the biological mechanisms through which infections would increase the risk for psychosis, including substance-induced psychosis, remain poorly understood.

“If the exact mechanisms underlying the psychotogenic properties of infections or the immune response can be identified, this is likely to lead to improvements in treatment for psychotic disorders. A further hope is that it may even be possible to use this knowledge for primary prevention of psychosis,” the authors wrote.

Interpret with caution

Commenting on the study, Ole Köhler-Forsberg, MD, from the Psychosis Research Unit, Aarhus University Hospital, Denmark, said in an interview that the findings support a potential immunologic link to schizophrenia. 

“However,” he added, “as in every register-based study, no causality can be assumed, only associations. As mentioned by the authors, there may be residual confounding and confounding by indication.”

Also commenting on the study, René Kahn, MD, PhD, professor and chair of psychiatry at the Icahn School of Medicine at Mount Sinai in New York, noted in an interview that there is a lot of “indirect evidence” from epidemiologic studies like this one to suggest an immune component to psychosis.  

“However, there is not a single piece of direct evidence linking the immune system to schizophrenia so far,” Dr. Kahn cautioned. 

“Yes, people who have hepatitis have a higher risk of developing substance-induced psychosis, but this may be a spurious finding. It may very well be that people who are prone to hepatitis for whatever reasons are at higher risk for psychosis but there is no direct evidence that the two are related. This study doesn’t convince me at all that immune pathology is related to schizophrenia,” Dr. Kahn said. 

The study was supported by a grant from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). The study authors, Dr. Kahn, and Dr. Köhler-Forsberg disclosed no relevant financial relationships.
 

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

Severe infection is linked to an increased risk of substance-induced psychosis and subsequent conversion to schizophrenia, new research suggests.

Results of the large, population-based study showed any infection was associated with a 30% increased risk for substance-induced psychosis. However, with more than a threefold increased risk for substance-induced psychosis, hepatitis was the infection most strongly linked to psychosis and the only infection associated with conversion to schizophrenia.

“Severe infections are associated with an increased risk of developing a substance-induced psychosis. Furthermore, hepatitis following substance-induced psychosis is associated with an increase in the risk of conversion to schizophrenia. Both of these observations support the hypothesis of an immunological component to psychosis,” wrote the investigators, led by Carsten Hjorthøj, PhD, MSc, Copenhagen Research Center for Mental Health, Denmark.

The study was published online Feb. 12 in the American Journal of Psychiatry. 

Mechanism still poorly understood

Previous research suggests that infection increases the risk for schizophrenia, but this new study is the first to investigate the association between infection and substance-induced psychosis.

Using Danish national registry data, the researchers analyzed data on all individuals born in Denmark since 1981. Of the 2,256,779 people, the researchers identified 3,618 cases of incident substance-induced psychosis.

Any infection increased the risk for substance-induced psychosis in the fully-adjusted model (hazard ratio = 1.30; 95% confidence interval, 1.22–1.39; P less than .001). The risk was doubled in the first 2 years following a severe infection and stayed elevated for more than 20 years. 

Hepatitis was the infection most strongly associated with substance-induced psychosis (HR = 3.42; 95% CI, 2.47–4.74; P less than .001) and only hepatitis predicted conversion to schizophrenia after substance-induced psychosis (HR = 1.87; 95% CI, 1.07–3.26; P = .03).

These results, the investigators note, “mirror previous findings on the association between infections and schizophrenia, including previous observations that the link is particularly strong for hepatitis.”

They also point out that the biological mechanisms through which infections would increase the risk for psychosis, including substance-induced psychosis, remain poorly understood.

“If the exact mechanisms underlying the psychotogenic properties of infections or the immune response can be identified, this is likely to lead to improvements in treatment for psychotic disorders. A further hope is that it may even be possible to use this knowledge for primary prevention of psychosis,” the authors wrote.

Interpret with caution

Commenting on the study, Ole Köhler-Forsberg, MD, from the Psychosis Research Unit, Aarhus University Hospital, Denmark, said in an interview that the findings support a potential immunologic link to schizophrenia. 

“However,” he added, “as in every register-based study, no causality can be assumed, only associations. As mentioned by the authors, there may be residual confounding and confounding by indication.”

Also commenting on the study, René Kahn, MD, PhD, professor and chair of psychiatry at the Icahn School of Medicine at Mount Sinai in New York, noted in an interview that there is a lot of “indirect evidence” from epidemiologic studies like this one to suggest an immune component to psychosis.  

“However, there is not a single piece of direct evidence linking the immune system to schizophrenia so far,” Dr. Kahn cautioned. 

“Yes, people who have hepatitis have a higher risk of developing substance-induced psychosis, but this may be a spurious finding. It may very well be that people who are prone to hepatitis for whatever reasons are at higher risk for psychosis but there is no direct evidence that the two are related. This study doesn’t convince me at all that immune pathology is related to schizophrenia,” Dr. Kahn said. 

The study was supported by a grant from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). The study authors, Dr. Kahn, and Dr. Köhler-Forsberg disclosed no relevant financial relationships.
 

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

Severe infection is linked to an increased risk of substance-induced psychosis and subsequent conversion to schizophrenia, new research suggests.

Results of the large, population-based study showed any infection was associated with a 30% increased risk for substance-induced psychosis. However, with more than a threefold increased risk for substance-induced psychosis, hepatitis was the infection most strongly linked to psychosis and the only infection associated with conversion to schizophrenia.

“Severe infections are associated with an increased risk of developing a substance-induced psychosis. Furthermore, hepatitis following substance-induced psychosis is associated with an increase in the risk of conversion to schizophrenia. Both of these observations support the hypothesis of an immunological component to psychosis,” wrote the investigators, led by Carsten Hjorthøj, PhD, MSc, Copenhagen Research Center for Mental Health, Denmark.

The study was published online Feb. 12 in the American Journal of Psychiatry. 

Mechanism still poorly understood

Previous research suggests that infection increases the risk for schizophrenia, but this new study is the first to investigate the association between infection and substance-induced psychosis.

Using Danish national registry data, the researchers analyzed data on all individuals born in Denmark since 1981. Of the 2,256,779 people, the researchers identified 3,618 cases of incident substance-induced psychosis.

Any infection increased the risk for substance-induced psychosis in the fully-adjusted model (hazard ratio = 1.30; 95% confidence interval, 1.22–1.39; P less than .001). The risk was doubled in the first 2 years following a severe infection and stayed elevated for more than 20 years. 

Hepatitis was the infection most strongly associated with substance-induced psychosis (HR = 3.42; 95% CI, 2.47–4.74; P less than .001) and only hepatitis predicted conversion to schizophrenia after substance-induced psychosis (HR = 1.87; 95% CI, 1.07–3.26; P = .03).

These results, the investigators note, “mirror previous findings on the association between infections and schizophrenia, including previous observations that the link is particularly strong for hepatitis.”

They also point out that the biological mechanisms through which infections would increase the risk for psychosis, including substance-induced psychosis, remain poorly understood.

“If the exact mechanisms underlying the psychotogenic properties of infections or the immune response can be identified, this is likely to lead to improvements in treatment for psychotic disorders. A further hope is that it may even be possible to use this knowledge for primary prevention of psychosis,” the authors wrote.

Interpret with caution

Commenting on the study, Ole Köhler-Forsberg, MD, from the Psychosis Research Unit, Aarhus University Hospital, Denmark, said in an interview that the findings support a potential immunologic link to schizophrenia. 

“However,” he added, “as in every register-based study, no causality can be assumed, only associations. As mentioned by the authors, there may be residual confounding and confounding by indication.”

Also commenting on the study, René Kahn, MD, PhD, professor and chair of psychiatry at the Icahn School of Medicine at Mount Sinai in New York, noted in an interview that there is a lot of “indirect evidence” from epidemiologic studies like this one to suggest an immune component to psychosis.  

“However, there is not a single piece of direct evidence linking the immune system to schizophrenia so far,” Dr. Kahn cautioned. 

“Yes, people who have hepatitis have a higher risk of developing substance-induced psychosis, but this may be a spurious finding. It may very well be that people who are prone to hepatitis for whatever reasons are at higher risk for psychosis but there is no direct evidence that the two are related. This study doesn’t convince me at all that immune pathology is related to schizophrenia,” Dr. Kahn said. 

The study was supported by a grant from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). The study authors, Dr. Kahn, and Dr. Köhler-Forsberg disclosed no relevant financial relationships.
 

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

Analysis of additional lung fluid samples confirms the presence of vitamin E acetate in patients with electronic-cigarette, or vaping, product use–associated lung injury, according to a report on 51 patients in 16 states.

The average age of the patients was 23 years; 69% were male.

The report extends previous work by the Centers for Disease Control and Prevention to test for harmful substances in bronchoalveolar-lavage (BAL) fluid obtained from patients with electronic-cigarette, or vaping, product use–associated lung injury (EVALI) as part of a strategy to understand and manage the recent outbreak of EVALI cases in the United States, wrote Benjamin C. Blount, PhD, of the Division of Laboratory Sciences at the CDC’s National Center for Environmental Health, and colleagues.

“CDC was addressing a serious outbreak of lung injury that was sometimes lethal; but after the first 10 weeks of the outbreak investigation, the cause was still unknown,” Dr. Blount said in an interview. “Possible theories could not be evaluated unless the laboratory could develop tests that could confidently connect exposure to lung injury. Detection of toxicants in bronchoalveolar-lavage fluid from patients with EVALI can provide direct information on exposure within the lung.”

In a study published in the New England Journal of Medicine, the researchers examined the BAL of 51 cases of EVALI from 16 states. They analyzed the samples for multiple toxicants, including vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes.

Overall, 77% of the patients reported using products containing THC, 67% reported using products containing nicotine, and 51% reported using both types.

Researchers found vitamin E acetate in 48 of the 51 patients (94%); no vitamin E acetate was found in the BAL of healthy controls. Coconut oil and limonene were found in one patient each, but none of the other toxicants was found in the samples from the patients or controls.

In addition, 47 of the 50 patients for whom data were available either had detectable tetrahydrocannabinol (THC) or its metabolites in their BAL fluid samples, or they reported vaping THC products within 90 days before they became ill. Nicotine or its metabolites were found in 30 of 47 patients (64%).

The study findings were limited by several factors, including the potential role of vitamin E acetate as a marker for exposure to other toxicants, the uncertainty of the role of aerosolized constituents formed when vitamin E acetate is heated, and the lack of data on the timing and burden of toxicant exposure, the investigators noted.

As for the next steps in research, “additional studies are needed to examine the respiratory effects of inhaling aerosolized vitamin E acetate and provide information on whether vitamin E acetate in isolation causes lung injury,” Dr. Blount explained. Analysis of the aerosol and gases generated by case-associated product fluids is ongoing.

“When CDC developed the BAL study for this response, we considered several possible toxicants in this investigation to find a possible cause of the outbreak,” Dr. Blount noted. “To accomplish the study, CDC’s Environmental Health Laboratory developed 12 analytical methods and validated them in less than 3 weeks because of the urgent nature of the emergency.”

Dr. Blount said he would advise clinicians to “continue to reference CDC guidance on treating suspected or EVALI patients.” In December, the CDC published updated guidance for clinicians on hospitalized EVALI patients. “Following this guidance and other recommendations could reduce EVALI-associated morbidity and mortality,” Dr. Blount said.

The study was supported in part by the National Cancer Institute, the FDA Center for Tobacco Products, and Ohio State University Pelotonia Intramural Research. The researchers had no financial conflicts to disclose.

SOURCE: Blount BC et al. N Engl J Med. 2020 Feb 20. doi: 10.1056/NEJMoa1916433.

Analysis of additional lung fluid samples confirms the presence of vitamin E acetate in patients with electronic-cigarette, or vaping, product use–associated lung injury, according to a report on 51 patients in 16 states.

The average age of the patients was 23 years; 69% were male.

The report extends previous work by the Centers for Disease Control and Prevention to test for harmful substances in bronchoalveolar-lavage (BAL) fluid obtained from patients with electronic-cigarette, or vaping, product use–associated lung injury (EVALI) as part of a strategy to understand and manage the recent outbreak of EVALI cases in the United States, wrote Benjamin C. Blount, PhD, of the Division of Laboratory Sciences at the CDC’s National Center for Environmental Health, and colleagues.

“CDC was addressing a serious outbreak of lung injury that was sometimes lethal; but after the first 10 weeks of the outbreak investigation, the cause was still unknown,” Dr. Blount said in an interview. “Possible theories could not be evaluated unless the laboratory could develop tests that could confidently connect exposure to lung injury. Detection of toxicants in bronchoalveolar-lavage fluid from patients with EVALI can provide direct information on exposure within the lung.”

In a study published in the New England Journal of Medicine, the researchers examined the BAL of 51 cases of EVALI from 16 states. They analyzed the samples for multiple toxicants, including vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes.

Overall, 77% of the patients reported using products containing THC, 67% reported using products containing nicotine, and 51% reported using both types.

Researchers found vitamin E acetate in 48 of the 51 patients (94%); no vitamin E acetate was found in the BAL of healthy controls. Coconut oil and limonene were found in one patient each, but none of the other toxicants was found in the samples from the patients or controls.

In addition, 47 of the 50 patients for whom data were available either had detectable tetrahydrocannabinol (THC) or its metabolites in their BAL fluid samples, or they reported vaping THC products within 90 days before they became ill. Nicotine or its metabolites were found in 30 of 47 patients (64%).

The study findings were limited by several factors, including the potential role of vitamin E acetate as a marker for exposure to other toxicants, the uncertainty of the role of aerosolized constituents formed when vitamin E acetate is heated, and the lack of data on the timing and burden of toxicant exposure, the investigators noted.

As for the next steps in research, “additional studies are needed to examine the respiratory effects of inhaling aerosolized vitamin E acetate and provide information on whether vitamin E acetate in isolation causes lung injury,” Dr. Blount explained. Analysis of the aerosol and gases generated by case-associated product fluids is ongoing.

“When CDC developed the BAL study for this response, we considered several possible toxicants in this investigation to find a possible cause of the outbreak,” Dr. Blount noted. “To accomplish the study, CDC’s Environmental Health Laboratory developed 12 analytical methods and validated them in less than 3 weeks because of the urgent nature of the emergency.”

Dr. Blount said he would advise clinicians to “continue to reference CDC guidance on treating suspected or EVALI patients.” In December, the CDC published updated guidance for clinicians on hospitalized EVALI patients. “Following this guidance and other recommendations could reduce EVALI-associated morbidity and mortality,” Dr. Blount said.

The study was supported in part by the National Cancer Institute, the FDA Center for Tobacco Products, and Ohio State University Pelotonia Intramural Research. The researchers had no financial conflicts to disclose.

SOURCE: Blount BC et al. N Engl J Med. 2020 Feb 20. doi: 10.1056/NEJMoa1916433.

Analysis of additional lung fluid samples confirms the presence of vitamin E acetate in patients with electronic-cigarette, or vaping, product use–associated lung injury, according to a report on 51 patients in 16 states.

The average age of the patients was 23 years; 69% were male.

The report extends previous work by the Centers for Disease Control and Prevention to test for harmful substances in bronchoalveolar-lavage (BAL) fluid obtained from patients with electronic-cigarette, or vaping, product use–associated lung injury (EVALI) as part of a strategy to understand and manage the recent outbreak of EVALI cases in the United States, wrote Benjamin C. Blount, PhD, of the Division of Laboratory Sciences at the CDC’s National Center for Environmental Health, and colleagues.

“CDC was addressing a serious outbreak of lung injury that was sometimes lethal; but after the first 10 weeks of the outbreak investigation, the cause was still unknown,” Dr. Blount said in an interview. “Possible theories could not be evaluated unless the laboratory could develop tests that could confidently connect exposure to lung injury. Detection of toxicants in bronchoalveolar-lavage fluid from patients with EVALI can provide direct information on exposure within the lung.”

In a study published in the New England Journal of Medicine, the researchers examined the BAL of 51 cases of EVALI from 16 states. They analyzed the samples for multiple toxicants, including vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes.

Overall, 77% of the patients reported using products containing THC, 67% reported using products containing nicotine, and 51% reported using both types.

Researchers found vitamin E acetate in 48 of the 51 patients (94%); no vitamin E acetate was found in the BAL of healthy controls. Coconut oil and limonene were found in one patient each, but none of the other toxicants was found in the samples from the patients or controls.

In addition, 47 of the 50 patients for whom data were available either had detectable tetrahydrocannabinol (THC) or its metabolites in their BAL fluid samples, or they reported vaping THC products within 90 days before they became ill. Nicotine or its metabolites were found in 30 of 47 patients (64%).

The study findings were limited by several factors, including the potential role of vitamin E acetate as a marker for exposure to other toxicants, the uncertainty of the role of aerosolized constituents formed when vitamin E acetate is heated, and the lack of data on the timing and burden of toxicant exposure, the investigators noted.

As for the next steps in research, “additional studies are needed to examine the respiratory effects of inhaling aerosolized vitamin E acetate and provide information on whether vitamin E acetate in isolation causes lung injury,” Dr. Blount explained. Analysis of the aerosol and gases generated by case-associated product fluids is ongoing.

“When CDC developed the BAL study for this response, we considered several possible toxicants in this investigation to find a possible cause of the outbreak,” Dr. Blount noted. “To accomplish the study, CDC’s Environmental Health Laboratory developed 12 analytical methods and validated them in less than 3 weeks because of the urgent nature of the emergency.”

Dr. Blount said he would advise clinicians to “continue to reference CDC guidance on treating suspected or EVALI patients.” In December, the CDC published updated guidance for clinicians on hospitalized EVALI patients. “Following this guidance and other recommendations could reduce EVALI-associated morbidity and mortality,” Dr. Blount said.

The study was supported in part by the National Cancer Institute, the FDA Center for Tobacco Products, and Ohio State University Pelotonia Intramural Research. The researchers had no financial conflicts to disclose.

SOURCE: Blount BC et al. N Engl J Med. 2020 Feb 20. doi: 10.1056/NEJMoa1916433.

A new tumor neoantigenicity metric may improve prediction of response to immunotherapy in patients with melanoma, lung cancer, and kidney cancer, a retrospective analysis suggests.

The new metric, known as the Cauchy-Schwarz index of neoantigens (CSiN) score, incorporates both immunogenicity and clonality, according to lead study author Tianshi Lu, a PhD candidate at the University of Texas Southwestern Medical Center in Dallas, and colleagues.

“The major biological insight from this study is that the neoantigen clonal structure in each tumor specimen and the immunogenicity of the neoantigens (represented by the MHC-binding strength in our study) are predictive of response to checkpoint inhibitors and prognosis,” the investigators wrote in Science Immunology.

The study involved 2,479 patients with various cancers, including immunogenic types such as renal cell carcinoma (RCC), and nonimmunogenic types, such as pediatric acute lymphocytic leukemia.

The investigators first evaluated CSiN in relation to clinical outcome among patients with immunogenic cancers who received immunotherapy. Drawing data from multiple cohorts, the investigators found that patients who had better responses to therapy were significantly more likely to have above average CSiN scores than those who had worse responses.

In one cohort of patients with melanoma who received anti–CTLA-4 therapy, those with better responses were more likely to have high CSiN scores (P = .009). In another cohort of melanoma patients who received anti–CTLA-4 therapy, those with higher CSiN scores were more likely to achieve durable clinical benefit (response or stable disease for more than 6 months), compared with patients who had lower CSiN scores (P = .033).

Among patients with clear cell RCC treated with anti-PD-1/PD-L1 therapy, there was a significant positive association between higher CSiN scores and better response (P = .036). Among T effector-high patients with metastatic clear cell RCC, there was a significant association between higher CSiN scores and better response to atezolizumab (P = .028) but not sunitinib (P = .890).

SOURCE: Lu et al. Sci Immunol. 2020 Feb 21. doi: 10.1126/sciimmunol.aaz3199.

A new tumor neoantigenicity metric may improve prediction of response to immunotherapy in patients with melanoma, lung cancer, and kidney cancer, a retrospective analysis suggests.

The new metric, known as the Cauchy-Schwarz index of neoantigens (CSiN) score, incorporates both immunogenicity and clonality, according to lead study author Tianshi Lu, a PhD candidate at the University of Texas Southwestern Medical Center in Dallas, and colleagues.

“The major biological insight from this study is that the neoantigen clonal structure in each tumor specimen and the immunogenicity of the neoantigens (represented by the MHC-binding strength in our study) are predictive of response to checkpoint inhibitors and prognosis,” the investigators wrote in Science Immunology.

The study involved 2,479 patients with various cancers, including immunogenic types such as renal cell carcinoma (RCC), and nonimmunogenic types, such as pediatric acute lymphocytic leukemia.

The investigators first evaluated CSiN in relation to clinical outcome among patients with immunogenic cancers who received immunotherapy. Drawing data from multiple cohorts, the investigators found that patients who had better responses to therapy were significantly more likely to have above average CSiN scores than those who had worse responses.

In one cohort of patients with melanoma who received anti–CTLA-4 therapy, those with better responses were more likely to have high CSiN scores (P = .009). In another cohort of melanoma patients who received anti–CTLA-4 therapy, those with higher CSiN scores were more likely to achieve durable clinical benefit (response or stable disease for more than 6 months), compared with patients who had lower CSiN scores (P = .033).

Among patients with clear cell RCC treated with anti-PD-1/PD-L1 therapy, there was a significant positive association between higher CSiN scores and better response (P = .036). Among T effector-high patients with metastatic clear cell RCC, there was a significant association between higher CSiN scores and better response to atezolizumab (P = .028) but not sunitinib (P = .890).

SOURCE: Lu et al. Sci Immunol. 2020 Feb 21. doi: 10.1126/sciimmunol.aaz3199.

A new tumor neoantigenicity metric may improve prediction of response to immunotherapy in patients with melanoma, lung cancer, and kidney cancer, a retrospective analysis suggests.

The new metric, known as the Cauchy-Schwarz index of neoantigens (CSiN) score, incorporates both immunogenicity and clonality, according to lead study author Tianshi Lu, a PhD candidate at the University of Texas Southwestern Medical Center in Dallas, and colleagues.

“The major biological insight from this study is that the neoantigen clonal structure in each tumor specimen and the immunogenicity of the neoantigens (represented by the MHC-binding strength in our study) are predictive of response to checkpoint inhibitors and prognosis,” the investigators wrote in Science Immunology.

The study involved 2,479 patients with various cancers, including immunogenic types such as renal cell carcinoma (RCC), and nonimmunogenic types, such as pediatric acute lymphocytic leukemia.

The investigators first evaluated CSiN in relation to clinical outcome among patients with immunogenic cancers who received immunotherapy. Drawing data from multiple cohorts, the investigators found that patients who had better responses to therapy were significantly more likely to have above average CSiN scores than those who had worse responses.

In one cohort of patients with melanoma who received anti–CTLA-4 therapy, those with better responses were more likely to have high CSiN scores (P = .009). In another cohort of melanoma patients who received anti–CTLA-4 therapy, those with higher CSiN scores were more likely to achieve durable clinical benefit (response or stable disease for more than 6 months), compared with patients who had lower CSiN scores (P = .033).

Among patients with clear cell RCC treated with anti-PD-1/PD-L1 therapy, there was a significant positive association between higher CSiN scores and better response (P = .036). Among T effector-high patients with metastatic clear cell RCC, there was a significant association between higher CSiN scores and better response to atezolizumab (P = .028) but not sunitinib (P = .890).

SOURCE: Lu et al. Sci Immunol. 2020 Feb 21. doi: 10.1126/sciimmunol.aaz3199.

Disturbance of tumor necrosis factor (TNF)–alpha and oxidative stress status may be involved in the pathophysiology of schizophrenia, new study results suggest.

In a study published in Psychoneuroendocrinology, the investigators collected blood samples from 119 patients with schizophrenia and 135 controls. Along with TNF-alpha, assays for the oxidative stress markers superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) were measured. The average illness duration in patients with schizophrenia was 8.23 months, and their average total Positive and Negative Syndrome Scale score was 87.64, reported Shiguang Zhu of Nanjing (China) Medical University and associates.

Serum levels of TNF-alpha and MDA were significantly higher (P = .007 for both), and GSH-Px levels were significantly lower (P = .005), in patients with schizophrenia, compared with controls, after Bonferroni correction. The interaction between GSH-Px and TNF-alpha was negatively associated with the presence of schizophrenia (odds ratio, 0.99; 95% confidence interval, 0.98-0.99; P = .001), and the interaction between MDA and TNF-alpha was positively associated with schizophrenia risk (OR, 1.61, 95% CI, 1.16-2.24, P = .004).

“It is worth[while] to note that [the] immune-inflammatory and oxidative stress hypothesis are just one of the theories for schizophrenic development, and other neurobiological theories such as neurodevelopmental dysfunction and hypothalamus-pituitary-adrenal axis hormones disturbance should be considered,” the investigators wrote. However, their study “suggests that TNF-alpha and disturbance of oxidative stress status as well as their interaction may be involved in the pathophysiology of schizophrenia.”

The study was supported by the National Natural Science Foundation of China, Shanghai Jiao Tong University Medical Engineering Foundation, Shanghai Jiao Tong University School of Medicine, and CAS Key Laboratory of Mental Health. The investigators reported that they had no conflicts of interest.

lfranki@mdedge.com

SOURCE: Zhu S et al. Psychoneuroendocrinology. 2020 Jan 30. doi: 10.1016/j.psyneuen.2020.104595.

Disturbance of tumor necrosis factor (TNF)–alpha and oxidative stress status may be involved in the pathophysiology of schizophrenia, new study results suggest.

In a study published in Psychoneuroendocrinology, the investigators collected blood samples from 119 patients with schizophrenia and 135 controls. Along with TNF-alpha, assays for the oxidative stress markers superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) were measured. The average illness duration in patients with schizophrenia was 8.23 months, and their average total Positive and Negative Syndrome Scale score was 87.64, reported Shiguang Zhu of Nanjing (China) Medical University and associates.

Serum levels of TNF-alpha and MDA were significantly higher (P = .007 for both), and GSH-Px levels were significantly lower (P = .005), in patients with schizophrenia, compared with controls, after Bonferroni correction. The interaction between GSH-Px and TNF-alpha was negatively associated with the presence of schizophrenia (odds ratio, 0.99; 95% confidence interval, 0.98-0.99; P = .001), and the interaction between MDA and TNF-alpha was positively associated with schizophrenia risk (OR, 1.61, 95% CI, 1.16-2.24, P = .004).

“It is worth[while] to note that [the] immune-inflammatory and oxidative stress hypothesis are just one of the theories for schizophrenic development, and other neurobiological theories such as neurodevelopmental dysfunction and hypothalamus-pituitary-adrenal axis hormones disturbance should be considered,” the investigators wrote. However, their study “suggests that TNF-alpha and disturbance of oxidative stress status as well as their interaction may be involved in the pathophysiology of schizophrenia.”

The study was supported by the National Natural Science Foundation of China, Shanghai Jiao Tong University Medical Engineering Foundation, Shanghai Jiao Tong University School of Medicine, and CAS Key Laboratory of Mental Health. The investigators reported that they had no conflicts of interest.

lfranki@mdedge.com

SOURCE: Zhu S et al. Psychoneuroendocrinology. 2020 Jan 30. doi: 10.1016/j.psyneuen.2020.104595.

Disturbance of tumor necrosis factor (TNF)–alpha and oxidative stress status may be involved in the pathophysiology of schizophrenia, new study results suggest.

In a study published in Psychoneuroendocrinology, the investigators collected blood samples from 119 patients with schizophrenia and 135 controls. Along with TNF-alpha, assays for the oxidative stress markers superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) were measured. The average illness duration in patients with schizophrenia was 8.23 months, and their average total Positive and Negative Syndrome Scale score was 87.64, reported Shiguang Zhu of Nanjing (China) Medical University and associates.

Serum levels of TNF-alpha and MDA were significantly higher (P = .007 for both), and GSH-Px levels were significantly lower (P = .005), in patients with schizophrenia, compared with controls, after Bonferroni correction. The interaction between GSH-Px and TNF-alpha was negatively associated with the presence of schizophrenia (odds ratio, 0.99; 95% confidence interval, 0.98-0.99; P = .001), and the interaction between MDA and TNF-alpha was positively associated with schizophrenia risk (OR, 1.61, 95% CI, 1.16-2.24, P = .004).

“It is worth[while] to note that [the] immune-inflammatory and oxidative stress hypothesis are just one of the theories for schizophrenic development, and other neurobiological theories such as neurodevelopmental dysfunction and hypothalamus-pituitary-adrenal axis hormones disturbance should be considered,” the investigators wrote. However, their study “suggests that TNF-alpha and disturbance of oxidative stress status as well as their interaction may be involved in the pathophysiology of schizophrenia.”

The study was supported by the National Natural Science Foundation of China, Shanghai Jiao Tong University Medical Engineering Foundation, Shanghai Jiao Tong University School of Medicine, and CAS Key Laboratory of Mental Health. The investigators reported that they had no conflicts of interest.

lfranki@mdedge.com

SOURCE: Zhu S et al. Psychoneuroendocrinology. 2020 Jan 30. doi: 10.1016/j.psyneuen.2020.104595.

The Food and Drug Administration has approved bempedoic acid (Nexletol) for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional LDL cholesterol lowering.

The oral adenosine triphosphate–citrate lyase (ACL) inhibitor is indicated as an adjunct to diet and maximally tolerated statin therapy in these patients, and approved at the 180 mg once daily dose, the agency announced today.

The safety and efficacy of bempedoic acid were demonstrated over 52 weeks in two multicenter randomized, clinical trials involving 3,009 adults with HeFH or established ASCVD on maximally tolerated statin therapy.

The difference between bempedoic acid and placebo for the primary outcome of change in LDL cholesterol from baseline to week 12 was –18% in the first trial, CLEAR Harmony (95% confidence interval, –20% to –16%; P less than .001), and –17% in the second trial, CLEAR Wisdom (95% CI, –21% to –14%; P less than .001).

The label notes that the effect on cardiovascular morbidity and mortality has not been determined. The label also includes warnings stating that bempedoic acid may increase blood uric acid levels and is associated with an increased risk of tendon rupture or injury.

In clinical trials, 26% of bempedoic acid–treated patients with normal baseline uric acid values versus 9.5% of placebo-treated patients experienced hyperuricemia one or more times, and 3.5% of patients experienced clinically significant hyperuricemia reported as an adverse reaction versus 1.1% with placebo, according to the label. Gout was reported in 1.5% of patients treated with bempedoic acid and 0.4% of those treated with placebo.

Also in clinical trials, the risk of tendon rupture was 0.5% with bempedoic acid and 0% with placebo. Tendon rupture involved the rotator cuff, biceps tendon, or Achilles tendon, and occurred within weeks to months of starting the drug. Rupture may “occur more frequently in patients over 60 years of age, in those taking corticosteroid or fluoroquinolone drugs, in patients with renal failure, and in patients with previous tendon disorders,” the label states.

The label also advises that patients avoid concomitant use of bempedoic acid with simvastatin greater than 20 mg or pravastatin greater than 40 mg because it causes an increase in statin concentrations and may increase the risk of related myopathy.

A decision is expected shortly on a new drug application submitted by Esperion for an LDL cholesterol–lowering indication for bempedoic acid 180 mg/ezetimibe 10 mg combination tablet.

Full prescribing information is available online.

This article first appeared on Medscape.com.

The Food and Drug Administration has approved bempedoic acid (Nexletol) for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional LDL cholesterol lowering.

The oral adenosine triphosphate–citrate lyase (ACL) inhibitor is indicated as an adjunct to diet and maximally tolerated statin therapy in these patients, and approved at the 180 mg once daily dose, the agency announced today.

The safety and efficacy of bempedoic acid were demonstrated over 52 weeks in two multicenter randomized, clinical trials involving 3,009 adults with HeFH or established ASCVD on maximally tolerated statin therapy.

The difference between bempedoic acid and placebo for the primary outcome of change in LDL cholesterol from baseline to week 12 was –18% in the first trial, CLEAR Harmony (95% confidence interval, –20% to –16%; P less than .001), and –17% in the second trial, CLEAR Wisdom (95% CI, –21% to –14%; P less than .001).

The label notes that the effect on cardiovascular morbidity and mortality has not been determined. The label also includes warnings stating that bempedoic acid may increase blood uric acid levels and is associated with an increased risk of tendon rupture or injury.

In clinical trials, 26% of bempedoic acid–treated patients with normal baseline uric acid values versus 9.5% of placebo-treated patients experienced hyperuricemia one or more times, and 3.5% of patients experienced clinically significant hyperuricemia reported as an adverse reaction versus 1.1% with placebo, according to the label. Gout was reported in 1.5% of patients treated with bempedoic acid and 0.4% of those treated with placebo.

Also in clinical trials, the risk of tendon rupture was 0.5% with bempedoic acid and 0% with placebo. Tendon rupture involved the rotator cuff, biceps tendon, or Achilles tendon, and occurred within weeks to months of starting the drug. Rupture may “occur more frequently in patients over 60 years of age, in those taking corticosteroid or fluoroquinolone drugs, in patients with renal failure, and in patients with previous tendon disorders,” the label states.

The label also advises that patients avoid concomitant use of bempedoic acid with simvastatin greater than 20 mg or pravastatin greater than 40 mg because it causes an increase in statin concentrations and may increase the risk of related myopathy.

A decision is expected shortly on a new drug application submitted by Esperion for an LDL cholesterol–lowering indication for bempedoic acid 180 mg/ezetimibe 10 mg combination tablet.

Full prescribing information is available online.

This article first appeared on Medscape.com.

The Food and Drug Administration has approved bempedoic acid (Nexletol) for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease (ASCVD) who require additional LDL cholesterol lowering.

The oral adenosine triphosphate–citrate lyase (ACL) inhibitor is indicated as an adjunct to diet and maximally tolerated statin therapy in these patients, and approved at the 180 mg once daily dose, the agency announced today.

The safety and efficacy of bempedoic acid were demonstrated over 52 weeks in two multicenter randomized, clinical trials involving 3,009 adults with HeFH or established ASCVD on maximally tolerated statin therapy.

The difference between bempedoic acid and placebo for the primary outcome of change in LDL cholesterol from baseline to week 12 was –18% in the first trial, CLEAR Harmony (95% confidence interval, –20% to –16%; P less than .001), and –17% in the second trial, CLEAR Wisdom (95% CI, –21% to –14%; P less than .001).

The label notes that the effect on cardiovascular morbidity and mortality has not been determined. The label also includes warnings stating that bempedoic acid may increase blood uric acid levels and is associated with an increased risk of tendon rupture or injury.

In clinical trials, 26% of bempedoic acid–treated patients with normal baseline uric acid values versus 9.5% of placebo-treated patients experienced hyperuricemia one or more times, and 3.5% of patients experienced clinically significant hyperuricemia reported as an adverse reaction versus 1.1% with placebo, according to the label. Gout was reported in 1.5% of patients treated with bempedoic acid and 0.4% of those treated with placebo.

Also in clinical trials, the risk of tendon rupture was 0.5% with bempedoic acid and 0% with placebo. Tendon rupture involved the rotator cuff, biceps tendon, or Achilles tendon, and occurred within weeks to months of starting the drug. Rupture may “occur more frequently in patients over 60 years of age, in those taking corticosteroid or fluoroquinolone drugs, in patients with renal failure, and in patients with previous tendon disorders,” the label states.

The label also advises that patients avoid concomitant use of bempedoic acid with simvastatin greater than 20 mg or pravastatin greater than 40 mg because it causes an increase in statin concentrations and may increase the risk of related myopathy.

A decision is expected shortly on a new drug application submitted by Esperion for an LDL cholesterol–lowering indication for bempedoic acid 180 mg/ezetimibe 10 mg combination tablet.

Full prescribing information is available online.

This article first appeared on Medscape.com.

Patients with schizophrenia have decreased chronnectomic density in the dorsolateral prefrontal cortex, compared with healthy controls, and cigarette smoking in patients with schizophrenia may be associated with a degree of preserved function in that brain region, researchers reported. The results indicate that smoking may be associated with a preservation effect, but it “cannot restore patients’ prefrontal dysfunction to normal levels,” the researchers said.

The chronnectome depicts how brain functional connectivity patterns (i.e., the connectome) vary over time. Prior research has suggested that the chronnectome is altered in patients with schizophrenia and in people with nicotine addiction. “Therefore, the chronnectome may be an effective index to evaluate the smoking-related prefrontal functional changes in schizophrenia,” said Yun-Shuang Fan, a researcher at the Clinical Hospital of Chengdu Brain Science Institute in China, and colleagues in the report, which was published in Progress in Neuro-Psychopharmacology & Biological Psychiatry.

The investigators studied 49 patients with schizophrenia, including 22 smokers and 27 nonsmokers, and 43 healthy controls, including 22 smokers and 21 nonsmokers. Participants underwent resting-state functional magnetic resonance imaging, and the researchers analyzed chronnectomic density using a sliding-window method. The investigators examined interactions between smoking status and diagnosis.

Smoking was associated with reduced chronnectomic density in healthy controls, but increased density in patients with schizophrenia. The study provides a “framework to elaborate upon the self-medication hypothesis in schizophrenia” and sheds “some fresh light on the elevated rates of smoking in schizophrenia,” they said.

The study was relatively small, and patients’ use of antipsychotic medications, which can affect the connectome, may limit the results. In addition, the study’s cross-sectional design precludes knowing whether “smoking behavior is the cause or result of the prefrontal chronnectome alterations in schizophrenia,” the authors added.

The study was supported by the National Natural Science Foundation of China and the Sichuan Science and Technology Program. The researchers had no conflicts of interest.

jremaly@mdedge.com

SOURCE: Fan YS et al. Prog Neuropsychopharmacol Biol Psychiatry. 2020 Apr 20. doi: 10.1016/j.pnpbp.2020.109860.

Patients with schizophrenia have decreased chronnectomic density in the dorsolateral prefrontal cortex, compared with healthy controls, and cigarette smoking in patients with schizophrenia may be associated with a degree of preserved function in that brain region, researchers reported. The results indicate that smoking may be associated with a preservation effect, but it “cannot restore patients’ prefrontal dysfunction to normal levels,” the researchers said.

The chronnectome depicts how brain functional connectivity patterns (i.e., the connectome) vary over time. Prior research has suggested that the chronnectome is altered in patients with schizophrenia and in people with nicotine addiction. “Therefore, the chronnectome may be an effective index to evaluate the smoking-related prefrontal functional changes in schizophrenia,” said Yun-Shuang Fan, a researcher at the Clinical Hospital of Chengdu Brain Science Institute in China, and colleagues in the report, which was published in Progress in Neuro-Psychopharmacology & Biological Psychiatry.

The investigators studied 49 patients with schizophrenia, including 22 smokers and 27 nonsmokers, and 43 healthy controls, including 22 smokers and 21 nonsmokers. Participants underwent resting-state functional magnetic resonance imaging, and the researchers analyzed chronnectomic density using a sliding-window method. The investigators examined interactions between smoking status and diagnosis.

Smoking was associated with reduced chronnectomic density in healthy controls, but increased density in patients with schizophrenia. The study provides a “framework to elaborate upon the self-medication hypothesis in schizophrenia” and sheds “some fresh light on the elevated rates of smoking in schizophrenia,” they said.

The study was relatively small, and patients’ use of antipsychotic medications, which can affect the connectome, may limit the results. In addition, the study’s cross-sectional design precludes knowing whether “smoking behavior is the cause or result of the prefrontal chronnectome alterations in schizophrenia,” the authors added.

The study was supported by the National Natural Science Foundation of China and the Sichuan Science and Technology Program. The researchers had no conflicts of interest.

jremaly@mdedge.com

SOURCE: Fan YS et al. Prog Neuropsychopharmacol Biol Psychiatry. 2020 Apr 20. doi: 10.1016/j.pnpbp.2020.109860.

Patients with schizophrenia have decreased chronnectomic density in the dorsolateral prefrontal cortex, compared with healthy controls, and cigarette smoking in patients with schizophrenia may be associated with a degree of preserved function in that brain region, researchers reported. The results indicate that smoking may be associated with a preservation effect, but it “cannot restore patients’ prefrontal dysfunction to normal levels,” the researchers said.

The chronnectome depicts how brain functional connectivity patterns (i.e., the connectome) vary over time. Prior research has suggested that the chronnectome is altered in patients with schizophrenia and in people with nicotine addiction. “Therefore, the chronnectome may be an effective index to evaluate the smoking-related prefrontal functional changes in schizophrenia,” said Yun-Shuang Fan, a researcher at the Clinical Hospital of Chengdu Brain Science Institute in China, and colleagues in the report, which was published in Progress in Neuro-Psychopharmacology & Biological Psychiatry.

The investigators studied 49 patients with schizophrenia, including 22 smokers and 27 nonsmokers, and 43 healthy controls, including 22 smokers and 21 nonsmokers. Participants underwent resting-state functional magnetic resonance imaging, and the researchers analyzed chronnectomic density using a sliding-window method. The investigators examined interactions between smoking status and diagnosis.

Smoking was associated with reduced chronnectomic density in healthy controls, but increased density in patients with schizophrenia. The study provides a “framework to elaborate upon the self-medication hypothesis in schizophrenia” and sheds “some fresh light on the elevated rates of smoking in schizophrenia,” they said.

The study was relatively small, and patients’ use of antipsychotic medications, which can affect the connectome, may limit the results. In addition, the study’s cross-sectional design precludes knowing whether “smoking behavior is the cause or result of the prefrontal chronnectome alterations in schizophrenia,” the authors added.

The study was supported by the National Natural Science Foundation of China and the Sichuan Science and Technology Program. The researchers had no conflicts of interest.

jremaly@mdedge.com

SOURCE: Fan YS et al. Prog Neuropsychopharmacol Biol Psychiatry. 2020 Apr 20. doi: 10.1016/j.pnpbp.2020.109860.