The Food and Drug Administration has cleared Abbott Laboratories’ next-generation Influenza A & B 2 and Strep A 2 molecular assays for point-of-care testing.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The Influenza A & B 2 assay can detect and differentiate influenza A and B in 13 minutes, with a call-out of positive results at 5 minutes. It can be stored at room temperature, simplifying storage and ordering. The Strep A 2 assay detects group A streptococcus bacterial nucleic acid in 6 minutes, with a call-out of positive results at 2 minutes. Both will be the fastest tests currently on the market in their respective fields, according to a corporate press release.

The assays will be available in a variety of inpatient and outpatient settings, particularly in locations where patients commonly access health care services, such as EDs, physician offices, walk-in clinics, and urgent care centers. This will allow health care providers to make a fast, informed diagnosis and provide appropriate treatment within the span of a single patient visit.

“The ability to obtain early call outs for positive test results with molecular accuracy in as little as 5 minutes for influenza and 2 minutes for strep A is a game-changing development that allows prompt treatment decisions at the point of care. Rapid testing may also help reduce improper antibiotic usage, which can occur when treatment is based exclusively on a patient’s symptoms, and contributes to antibiotic resistance,” Gregory J. Berry, PhD, director of molecular diagnostics at Northwell Health Laboratories in Lake Success, N.Y., said in the press release.

Find the full press release on the Abbott Laboratories website.

[email protected]

The Food and Drug Administration has cleared Abbott Laboratories’ next-generation Influenza A & B 2 and Strep A 2 molecular assays for point-of-care testing.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The Influenza A & B 2 assay can detect and differentiate influenza A and B in 13 minutes, with a call-out of positive results at 5 minutes. It can be stored at room temperature, simplifying storage and ordering. The Strep A 2 assay detects group A streptococcus bacterial nucleic acid in 6 minutes, with a call-out of positive results at 2 minutes. Both will be the fastest tests currently on the market in their respective fields, according to a corporate press release.

The assays will be available in a variety of inpatient and outpatient settings, particularly in locations where patients commonly access health care services, such as EDs, physician offices, walk-in clinics, and urgent care centers. This will allow health care providers to make a fast, informed diagnosis and provide appropriate treatment within the span of a single patient visit.

“The ability to obtain early call outs for positive test results with molecular accuracy in as little as 5 minutes for influenza and 2 minutes for strep A is a game-changing development that allows prompt treatment decisions at the point of care. Rapid testing may also help reduce improper antibiotic usage, which can occur when treatment is based exclusively on a patient’s symptoms, and contributes to antibiotic resistance,” Gregory J. Berry, PhD, director of molecular diagnostics at Northwell Health Laboratories in Lake Success, N.Y., said in the press release.

Find the full press release on the Abbott Laboratories website.

[email protected]

The Food and Drug Administration has cleared Abbott Laboratories’ next-generation Influenza A & B 2 and Strep A 2 molecular assays for point-of-care testing.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The Influenza A & B 2 assay can detect and differentiate influenza A and B in 13 minutes, with a call-out of positive results at 5 minutes. It can be stored at room temperature, simplifying storage and ordering. The Strep A 2 assay detects group A streptococcus bacterial nucleic acid in 6 minutes, with a call-out of positive results at 2 minutes. Both will be the fastest tests currently on the market in their respective fields, according to a corporate press release.

The assays will be available in a variety of inpatient and outpatient settings, particularly in locations where patients commonly access health care services, such as EDs, physician offices, walk-in clinics, and urgent care centers. This will allow health care providers to make a fast, informed diagnosis and provide appropriate treatment within the span of a single patient visit.

“The ability to obtain early call outs for positive test results with molecular accuracy in as little as 5 minutes for influenza and 2 minutes for strep A is a game-changing development that allows prompt treatment decisions at the point of care. Rapid testing may also help reduce improper antibiotic usage, which can occur when treatment is based exclusively on a patient’s symptoms, and contributes to antibiotic resistance,” Gregory J. Berry, PhD, director of molecular diagnostics at Northwell Health Laboratories in Lake Success, N.Y., said in the press release.

Find the full press release on the Abbott Laboratories website.

[email protected]

Clinicians consulting the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices vaccination schedules for children, adolescents, and adults in 2019 will find a simpler design and more useful product, according to David Kim, MD, of the Immunization Services Division of the Centers for Disease Control and Prevention, Atlanta.

In a single vote to cover both adult and child/adolescent schedules, the committee voted unanimously in favor of a redesign of the schedules and several clinical updates.

In 2016, the working group for vaccination schedules conducted an ad hoc evaluation of the adult schedule to assess its usability, Dr. Kim said at a meeting of the CDC’s ACIP.

The design of the adult schedule was fully evaluated in 2018 via a three-step process – interviews with 48 health care providers, a redesign of the schedule, and a survey after the redesign. Design changes to the child/adolescent schedule were harmonized with the adult schedule, Dr. Kim explained.

The adult vaccination schedule itself includes several updates in ACIP recommendations in addition to the aesthetic design changes.

The 2019 Adult Immunization Schedule includes the option of the live attenuated influenza vaccine (LAIV) for influenza, the addition of homelessness as an indication for hepatitis A vaccination, and the use of CpG-adjuvanted hepatitis B vaccine, Dr. Kim said.

The additions to the 2019 Child and Adolescent Immunization Schedule are the optional use of the LAIV for influenza, the addition of homelessness as an indication for hepatitis A vaccination, the use of CpG-adjuvanted hepatitis B vaccine (a cytosine phosphoguanosine oligodeoxynucleotide adjuvant), and the addition of the Tdap vaccination of individuals who received Tdap at age 7-10 years.

Some of the key design changes include the use of bright purple on the child/adolescent schedule to more easily distinguish it from the adult version, said Dr. Kim.

Other changes to both schedules include shorter titles, lists of vaccines and trade names, and compartmentalized information for easier reference. Figures have been replaced by tables, and footnotes are simply “Notes” at the end of the schedule, compartmentalized for easier reading, he said. In addition, the schedules include resources for vaccination in outbreak situations and a section on how to report vaccine preventable disease outbreaks.

The ACIP committee members had no relevant financial conflicts to disclose.

Clinicians consulting the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices vaccination schedules for children, adolescents, and adults in 2019 will find a simpler design and more useful product, according to David Kim, MD, of the Immunization Services Division of the Centers for Disease Control and Prevention, Atlanta.

In a single vote to cover both adult and child/adolescent schedules, the committee voted unanimously in favor of a redesign of the schedules and several clinical updates.

In 2016, the working group for vaccination schedules conducted an ad hoc evaluation of the adult schedule to assess its usability, Dr. Kim said at a meeting of the CDC’s ACIP.

The design of the adult schedule was fully evaluated in 2018 via a three-step process – interviews with 48 health care providers, a redesign of the schedule, and a survey after the redesign. Design changes to the child/adolescent schedule were harmonized with the adult schedule, Dr. Kim explained.

The adult vaccination schedule itself includes several updates in ACIP recommendations in addition to the aesthetic design changes.

The 2019 Adult Immunization Schedule includes the option of the live attenuated influenza vaccine (LAIV) for influenza, the addition of homelessness as an indication for hepatitis A vaccination, and the use of CpG-adjuvanted hepatitis B vaccine, Dr. Kim said.

The additions to the 2019 Child and Adolescent Immunization Schedule are the optional use of the LAIV for influenza, the addition of homelessness as an indication for hepatitis A vaccination, the use of CpG-adjuvanted hepatitis B vaccine (a cytosine phosphoguanosine oligodeoxynucleotide adjuvant), and the addition of the Tdap vaccination of individuals who received Tdap at age 7-10 years.

Some of the key design changes include the use of bright purple on the child/adolescent schedule to more easily distinguish it from the adult version, said Dr. Kim.

Other changes to both schedules include shorter titles, lists of vaccines and trade names, and compartmentalized information for easier reference. Figures have been replaced by tables, and footnotes are simply “Notes” at the end of the schedule, compartmentalized for easier reading, he said. In addition, the schedules include resources for vaccination in outbreak situations and a section on how to report vaccine preventable disease outbreaks.

The ACIP committee members had no relevant financial conflicts to disclose.

Clinicians consulting the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices vaccination schedules for children, adolescents, and adults in 2019 will find a simpler design and more useful product, according to David Kim, MD, of the Immunization Services Division of the Centers for Disease Control and Prevention, Atlanta.

In a single vote to cover both adult and child/adolescent schedules, the committee voted unanimously in favor of a redesign of the schedules and several clinical updates.

In 2016, the working group for vaccination schedules conducted an ad hoc evaluation of the adult schedule to assess its usability, Dr. Kim said at a meeting of the CDC’s ACIP.

The design of the adult schedule was fully evaluated in 2018 via a three-step process – interviews with 48 health care providers, a redesign of the schedule, and a survey after the redesign. Design changes to the child/adolescent schedule were harmonized with the adult schedule, Dr. Kim explained.

The adult vaccination schedule itself includes several updates in ACIP recommendations in addition to the aesthetic design changes.

The 2019 Adult Immunization Schedule includes the option of the live attenuated influenza vaccine (LAIV) for influenza, the addition of homelessness as an indication for hepatitis A vaccination, and the use of CpG-adjuvanted hepatitis B vaccine, Dr. Kim said.

The additions to the 2019 Child and Adolescent Immunization Schedule are the optional use of the LAIV for influenza, the addition of homelessness as an indication for hepatitis A vaccination, the use of CpG-adjuvanted hepatitis B vaccine (a cytosine phosphoguanosine oligodeoxynucleotide adjuvant), and the addition of the Tdap vaccination of individuals who received Tdap at age 7-10 years.

Some of the key design changes include the use of bright purple on the child/adolescent schedule to more easily distinguish it from the adult version, said Dr. Kim.

Other changes to both schedules include shorter titles, lists of vaccines and trade names, and compartmentalized information for easier reference. Figures have been replaced by tables, and footnotes are simply “Notes” at the end of the schedule, compartmentalized for easier reading, he said. In addition, the schedules include resources for vaccination in outbreak situations and a section on how to report vaccine preventable disease outbreaks.

The ACIP committee members had no relevant financial conflicts to disclose.

By the time you receive this issue, we will know election results. The effects on medical care, medical coverage, Medicare, and Medicaid will be profound. American medicine is integrally linked to Congress and the Supreme Court because on July 30, 1965, Lyndon Johnson signed Title 18 of the Social Security Act and created Medicare – a move that took medical care out of personal law and into public law.

In November, CMS will publish its “final rule” about documentation and reimbursement changes, site of service reimbursement, and several other impactful policy changes. We have an extended article from the AGA Partners in Value conference about these potential changes.

This month we highlight the medical home concept for IBD – an idea that is gaining traction. More intense colon cancer screening may be needed for families with nonhereditary colon cancer. An interesting article from JAMA suggests that obesity may play a role in colon cancer rates in young women.

Antibiotic resistance in H. pylori infections is reaching alarming levels and this information may alter our practice. We feature an “In Focus” section on endoscopic treatment for obese patients. We also continue highlighting some popular and interesting discussion chains emanating from the AGA Community.

Please stay involved as leaders in health care economics, delivery, and politics. We need thoughtful discussions and we need to bring patient stories to our politicians. It often seems that our advocacy does little to alter the national debate but who better to speak for the people that entrust us with their care?

John I. Allen, MD, MBA, AGAF

Editor in Chief

By the time you receive this issue, we will know election results. The effects on medical care, medical coverage, Medicare, and Medicaid will be profound. American medicine is integrally linked to Congress and the Supreme Court because on July 30, 1965, Lyndon Johnson signed Title 18 of the Social Security Act and created Medicare – a move that took medical care out of personal law and into public law.

In November, CMS will publish its “final rule” about documentation and reimbursement changes, site of service reimbursement, and several other impactful policy changes. We have an extended article from the AGA Partners in Value conference about these potential changes.

This month we highlight the medical home concept for IBD – an idea that is gaining traction. More intense colon cancer screening may be needed for families with nonhereditary colon cancer. An interesting article from JAMA suggests that obesity may play a role in colon cancer rates in young women.

Antibiotic resistance in H. pylori infections is reaching alarming levels and this information may alter our practice. We feature an “In Focus” section on endoscopic treatment for obese patients. We also continue highlighting some popular and interesting discussion chains emanating from the AGA Community.

Please stay involved as leaders in health care economics, delivery, and politics. We need thoughtful discussions and we need to bring patient stories to our politicians. It often seems that our advocacy does little to alter the national debate but who better to speak for the people that entrust us with their care?

John I. Allen, MD, MBA, AGAF

Editor in Chief

By the time you receive this issue, we will know election results. The effects on medical care, medical coverage, Medicare, and Medicaid will be profound. American medicine is integrally linked to Congress and the Supreme Court because on July 30, 1965, Lyndon Johnson signed Title 18 of the Social Security Act and created Medicare – a move that took medical care out of personal law and into public law.

In November, CMS will publish its “final rule” about documentation and reimbursement changes, site of service reimbursement, and several other impactful policy changes. We have an extended article from the AGA Partners in Value conference about these potential changes.

This month we highlight the medical home concept for IBD – an idea that is gaining traction. More intense colon cancer screening may be needed for families with nonhereditary colon cancer. An interesting article from JAMA suggests that obesity may play a role in colon cancer rates in young women.

Antibiotic resistance in H. pylori infections is reaching alarming levels and this information may alter our practice. We feature an “In Focus” section on endoscopic treatment for obese patients. We also continue highlighting some popular and interesting discussion chains emanating from the AGA Community.

Please stay involved as leaders in health care economics, delivery, and politics. We need thoughtful discussions and we need to bring patient stories to our politicians. It often seems that our advocacy does little to alter the national debate but who better to speak for the people that entrust us with their care?

John I. Allen, MD, MBA, AGAF

Editor in Chief

SAN FRANCISCO – A new analysis of cholera strains suggests that bacteriophages – viruses that prey on bacteria – are engaged in an evolutionary arms race with the Vibrio cholerae bacteria, and the dynamic between the two organisms may be an important factor in determining which strain of cholera goes on to cause a pandemic.

CDC

The work, presented by Kim Seed, PhD, at IDWeek, an annual scientific meeting on infectious diseases, examined a defense mechanism in V. cholerae, called phage inducible chromosomal island like element (PLE), as well as a unique mechanism in the bacteriophage to counter it. The work adds insight into the cholera strains that could emerge to produce future epidemics, and could even inform the use of bacteriophages as prophylactic agents to counter V. cholerae infection

In her talk, Dr. Seed described the dynamics of the current cholera pandemic, which is the seventh in recorded history and began in the 1960s. Over the past 100 years, six previous strains arose and then vanished, yielding each time to a new strain that became the predominant cholera-causing agent.

“This pattern of evolution, this so-called disappearing act, drives my research – I’m trying to understand what factors promote the evolution of novel genetic variants, and what factors contribute to why those variants disappear,” said Dr. Seed.

That quest brought her to the Bay of Bengal and Bangladesh. Genetic studies have shown this region to be the epicenter of cholera strains. It appears that cholera strains evolve there and then invade other regions of the world as a result of human travel and activity. Go to places in Africa or Asia where there is a cholera outbreak, and you can find cholera bacteria in the water that has the potential to cause human disease – but it won’t be the strain that is causing disease nearby. “(The culprit) is these introduced strains that come from Southeast Asia,” said Dr. Seed.

So her team went to Bangladesh, and studied cholera bacteria isolated from patients at the International Centre for Diarrhoeal Disease Research. The current strain is antibiotic resistant, as has been well documented. But Dr. Seed was interested in bacteriophages – viruses that prey on bacteria – because they live in the water supply and can also be isolated from the stool of cholera-infected patients, and it seemed likely that they could be an important selective force.

Indeed, her team found only a few bacteriophages that prey on V. cholerae in the samples from this hospital, and one type predominated in samples collected between 2001 and 2017; a bacteriophage known as ICP1. “This set up a very nice dynamic to be able to study the molecular mechanisms by which co-evolution was occurring in this one specific phage and Vibrio cholerae,” said Dr. Seed.

Genetic analysis revealed a mobile genetic element in V. cholerae – PLE –that conferred specific resistance against ICP1. After an infection, one of the bacteriophage’s proteins leads to excision and transcription of PLE. That produces a predicted 25 proteins, which in turn interfere with ICP1 through an as yet undetermined mechanism. But it’s effective, completely shutting down bacteriophage replication.

That couldn’t be the end of the story, Dr. Seed reasoned. Otherwise the bacteriophage would die out entirely for lack of a vulnerable host. More searching revealed the biggest surprise of all – ICP1, even though it is a virus, contains a complete suite of CRISPR (clustered regularly interspaced short palindromic repeats) apparatus that directly targets the PLE sequence. CRISPR is currently all the rage as a potential tool for genetic modification. It was discovered in bacteria, as a sort of immune response against bacteriophages. The CRISPR DNA contains a guide sequence that is complementary to and binds viral DNA, and then recruits other proteins to destroy the viral blueprint.

But here, for the first and only time, Dr. Seed’s team found that a bacteriophage had turned the tables, somehow capturing a CRISPR system of its own and turning it against its host’s defense system. Soon after infection, PLE switches on in response to its bacteriophage trigger, but the ICP1 counters by activating its CRISPR system, which is effective enough to allow the bacteriophage to reproduce.

The researchers then examined historical samples, and found another surprise: The appearance of CRISPR in ICP1 predated the appearance of the PLE variant that it targeted in V. cholerae. A little more digging revealed older variants of PLE, now gone from the V. cholerae population. “This explains why ICP1 had to have CRISPR, so it could overcome these previously prevalent genetic variants,” said Dr. Seed.

All told, the researchers found five unique PLE variants dating back to 1931, and the co-evolution of V. cholerae and ICP1 no doubt stretch much farther into the dim past. More recently, they found that previous strains of V. cholerae that went extinct also had different variations of PLE, suggesting that it may have been a temporary evolutionary victory by ICP1 over a PLE variant that caused the demise of an existing V. cholerae strain. But each time, it seems the bacteria responded with a new PLE variant, prolonging the arms race.

The work has the potential to affect other bacterial diseases, since most bacteria have phages that prey on them. “I have no doubt that they are a strong presence and selective force on all pathogens. People haven’t done so much work on that yet, but I think it’s coming,” said Dr. Seed.

SOURCE: Seed K. et al. ID Week 2018. Abstract 954.

SAN FRANCISCO – A new analysis of cholera strains suggests that bacteriophages – viruses that prey on bacteria – are engaged in an evolutionary arms race with the Vibrio cholerae bacteria, and the dynamic between the two organisms may be an important factor in determining which strain of cholera goes on to cause a pandemic.

CDC

The work, presented by Kim Seed, PhD, at IDWeek, an annual scientific meeting on infectious diseases, examined a defense mechanism in V. cholerae, called phage inducible chromosomal island like element (PLE), as well as a unique mechanism in the bacteriophage to counter it. The work adds insight into the cholera strains that could emerge to produce future epidemics, and could even inform the use of bacteriophages as prophylactic agents to counter V. cholerae infection

In her talk, Dr. Seed described the dynamics of the current cholera pandemic, which is the seventh in recorded history and began in the 1960s. Over the past 100 years, six previous strains arose and then vanished, yielding each time to a new strain that became the predominant cholera-causing agent.

“This pattern of evolution, this so-called disappearing act, drives my research – I’m trying to understand what factors promote the evolution of novel genetic variants, and what factors contribute to why those variants disappear,” said Dr. Seed.

That quest brought her to the Bay of Bengal and Bangladesh. Genetic studies have shown this region to be the epicenter of cholera strains. It appears that cholera strains evolve there and then invade other regions of the world as a result of human travel and activity. Go to places in Africa or Asia where there is a cholera outbreak, and you can find cholera bacteria in the water that has the potential to cause human disease – but it won’t be the strain that is causing disease nearby. “(The culprit) is these introduced strains that come from Southeast Asia,” said Dr. Seed.

So her team went to Bangladesh, and studied cholera bacteria isolated from patients at the International Centre for Diarrhoeal Disease Research. The current strain is antibiotic resistant, as has been well documented. But Dr. Seed was interested in bacteriophages – viruses that prey on bacteria – because they live in the water supply and can also be isolated from the stool of cholera-infected patients, and it seemed likely that they could be an important selective force.

Indeed, her team found only a few bacteriophages that prey on V. cholerae in the samples from this hospital, and one type predominated in samples collected between 2001 and 2017; a bacteriophage known as ICP1. “This set up a very nice dynamic to be able to study the molecular mechanisms by which co-evolution was occurring in this one specific phage and Vibrio cholerae,” said Dr. Seed.

Genetic analysis revealed a mobile genetic element in V. cholerae – PLE –that conferred specific resistance against ICP1. After an infection, one of the bacteriophage’s proteins leads to excision and transcription of PLE. That produces a predicted 25 proteins, which in turn interfere with ICP1 through an as yet undetermined mechanism. But it’s effective, completely shutting down bacteriophage replication.

That couldn’t be the end of the story, Dr. Seed reasoned. Otherwise the bacteriophage would die out entirely for lack of a vulnerable host. More searching revealed the biggest surprise of all – ICP1, even though it is a virus, contains a complete suite of CRISPR (clustered regularly interspaced short palindromic repeats) apparatus that directly targets the PLE sequence. CRISPR is currently all the rage as a potential tool for genetic modification. It was discovered in bacteria, as a sort of immune response against bacteriophages. The CRISPR DNA contains a guide sequence that is complementary to and binds viral DNA, and then recruits other proteins to destroy the viral blueprint.

But here, for the first and only time, Dr. Seed’s team found that a bacteriophage had turned the tables, somehow capturing a CRISPR system of its own and turning it against its host’s defense system. Soon after infection, PLE switches on in response to its bacteriophage trigger, but the ICP1 counters by activating its CRISPR system, which is effective enough to allow the bacteriophage to reproduce.

The researchers then examined historical samples, and found another surprise: The appearance of CRISPR in ICP1 predated the appearance of the PLE variant that it targeted in V. cholerae. A little more digging revealed older variants of PLE, now gone from the V. cholerae population. “This explains why ICP1 had to have CRISPR, so it could overcome these previously prevalent genetic variants,” said Dr. Seed.

All told, the researchers found five unique PLE variants dating back to 1931, and the co-evolution of V. cholerae and ICP1 no doubt stretch much farther into the dim past. More recently, they found that previous strains of V. cholerae that went extinct also had different variations of PLE, suggesting that it may have been a temporary evolutionary victory by ICP1 over a PLE variant that caused the demise of an existing V. cholerae strain. But each time, it seems the bacteria responded with a new PLE variant, prolonging the arms race.

The work has the potential to affect other bacterial diseases, since most bacteria have phages that prey on them. “I have no doubt that they are a strong presence and selective force on all pathogens. People haven’t done so much work on that yet, but I think it’s coming,” said Dr. Seed.

SOURCE: Seed K. et al. ID Week 2018. Abstract 954.

SAN FRANCISCO – A new analysis of cholera strains suggests that bacteriophages – viruses that prey on bacteria – are engaged in an evolutionary arms race with the Vibrio cholerae bacteria, and the dynamic between the two organisms may be an important factor in determining which strain of cholera goes on to cause a pandemic.

CDC

The work, presented by Kim Seed, PhD, at IDWeek, an annual scientific meeting on infectious diseases, examined a defense mechanism in V. cholerae, called phage inducible chromosomal island like element (PLE), as well as a unique mechanism in the bacteriophage to counter it. The work adds insight into the cholera strains that could emerge to produce future epidemics, and could even inform the use of bacteriophages as prophylactic agents to counter V. cholerae infection

In her talk, Dr. Seed described the dynamics of the current cholera pandemic, which is the seventh in recorded history and began in the 1960s. Over the past 100 years, six previous strains arose and then vanished, yielding each time to a new strain that became the predominant cholera-causing agent.

“This pattern of evolution, this so-called disappearing act, drives my research – I’m trying to understand what factors promote the evolution of novel genetic variants, and what factors contribute to why those variants disappear,” said Dr. Seed.

That quest brought her to the Bay of Bengal and Bangladesh. Genetic studies have shown this region to be the epicenter of cholera strains. It appears that cholera strains evolve there and then invade other regions of the world as a result of human travel and activity. Go to places in Africa or Asia where there is a cholera outbreak, and you can find cholera bacteria in the water that has the potential to cause human disease – but it won’t be the strain that is causing disease nearby. “(The culprit) is these introduced strains that come from Southeast Asia,” said Dr. Seed.

So her team went to Bangladesh, and studied cholera bacteria isolated from patients at the International Centre for Diarrhoeal Disease Research. The current strain is antibiotic resistant, as has been well documented. But Dr. Seed was interested in bacteriophages – viruses that prey on bacteria – because they live in the water supply and can also be isolated from the stool of cholera-infected patients, and it seemed likely that they could be an important selective force.

Indeed, her team found only a few bacteriophages that prey on V. cholerae in the samples from this hospital, and one type predominated in samples collected between 2001 and 2017; a bacteriophage known as ICP1. “This set up a very nice dynamic to be able to study the molecular mechanisms by which co-evolution was occurring in this one specific phage and Vibrio cholerae,” said Dr. Seed.

Genetic analysis revealed a mobile genetic element in V. cholerae – PLE –that conferred specific resistance against ICP1. After an infection, one of the bacteriophage’s proteins leads to excision and transcription of PLE. That produces a predicted 25 proteins, which in turn interfere with ICP1 through an as yet undetermined mechanism. But it’s effective, completely shutting down bacteriophage replication.

That couldn’t be the end of the story, Dr. Seed reasoned. Otherwise the bacteriophage would die out entirely for lack of a vulnerable host. More searching revealed the biggest surprise of all – ICP1, even though it is a virus, contains a complete suite of CRISPR (clustered regularly interspaced short palindromic repeats) apparatus that directly targets the PLE sequence. CRISPR is currently all the rage as a potential tool for genetic modification. It was discovered in bacteria, as a sort of immune response against bacteriophages. The CRISPR DNA contains a guide sequence that is complementary to and binds viral DNA, and then recruits other proteins to destroy the viral blueprint.

But here, for the first and only time, Dr. Seed’s team found that a bacteriophage had turned the tables, somehow capturing a CRISPR system of its own and turning it against its host’s defense system. Soon after infection, PLE switches on in response to its bacteriophage trigger, but the ICP1 counters by activating its CRISPR system, which is effective enough to allow the bacteriophage to reproduce.

The researchers then examined historical samples, and found another surprise: The appearance of CRISPR in ICP1 predated the appearance of the PLE variant that it targeted in V. cholerae. A little more digging revealed older variants of PLE, now gone from the V. cholerae population. “This explains why ICP1 had to have CRISPR, so it could overcome these previously prevalent genetic variants,” said Dr. Seed.

All told, the researchers found five unique PLE variants dating back to 1931, and the co-evolution of V. cholerae and ICP1 no doubt stretch much farther into the dim past. More recently, they found that previous strains of V. cholerae that went extinct also had different variations of PLE, suggesting that it may have been a temporary evolutionary victory by ICP1 over a PLE variant that caused the demise of an existing V. cholerae strain. But each time, it seems the bacteria responded with a new PLE variant, prolonging the arms race.

The work has the potential to affect other bacterial diseases, since most bacteria have phages that prey on them. “I have no doubt that they are a strong presence and selective force on all pathogens. People haven’t done so much work on that yet, but I think it’s coming,” said Dr. Seed.

SOURCE: Seed K. et al. ID Week 2018. Abstract 954.

Obesity and weight gain are linked to increased risk of colorectal cancer in younger women, according to an analysis of a large, prospective U.S. cohort study.

Young women who were obese had a nearly twofold increase in risk of early-onset colorectal cancer, compared with women of normal weight, authors of the study reported in JAMA Oncology.

The findings suggest body weight could be used to “personalize and complement” early cancer screening strategies among adults younger than 50 years, said investigator Po-Hong Liu, MD, of Washington University, St. Louis, and coauthors.

“Given that most of these younger cases are diagnosed symptomatically with more advanced tumors and with a significant influence on years of life lost, our findings reinforce the benefits of maintaining a healthy weight throughout life,” Dr. Liu and coinvestigators said in their report.

Their analysis was based on the ongoing Nurses Health Study II, which began in 1989 and enrolled a total of 116,430 women between the ages of 25 and 42 years in 14 U.S. states. Women completed questionnaires on demographics, medical and health information, and lifestyle factors every 2 years after enrollment.

Dr. Liu and colleagues were able to document 114 cases of colorectal cancer over a median of 13.9 years of follow-up in 85,256 women who had no cancer or inflammatory bowel disease when they were enrolled in the study. The median age at diagnosis for these cancers was 45 years.

Obesity was independently associated with increased risk of these early-onset colorectal cancers, the investigators found in multivariable analysis.

Women with a body mass index of 30 kg/m² or higher had a relative risk of 1.93 (95% confidence interval, 1.15-3.25) versus women with normal BMIs in the 18.5 to 22.9-kg/m² range, according to results of the analysis, they reported.

There was an apparent linear trend between increasing weight and increasing colorectal cancer risk, they added in their report.

They also found links between BMI in early adulthood and risk of early-onset colorectal cancer, including a relative risk of 1.63 for women who reported a BMI of 23 kg/m² or higher at 18 years of age, versus women with a BMI of 18.5-20.9 kg/m² at that age.

Similarly, increase in weight since early adulthood was associated with increased cancer risk, they reported.

While the link between excess weight and colorectal cancer incidence and mortality is well established in previous studies, this study is one of few reports looking at the association in younger individuals, according to Dr. Liu and colleagues.

This is thought to be the first prospective study looking at the link between obesity and risk of colo-rectal cancer diagnosed before the age of 50, they added.

The study was funded by grants from the National Institutes of Health. Dr. Liu had no conflict of interest disclosures related to the study. One coauthor reported consulting fees from Bayer Pharma AG, Janssen, and Pfizer.

[email protected]

SOURCE: Liu P-H et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4280.

AGA Resource 

Visit the AGA GI Patient Center for education to share with your patients about obesity, colorectal cancer and other GI disorders at patient.gastro.org.

Obesity and weight gain are linked to increased risk of colorectal cancer in younger women, according to an analysis of a large, prospective U.S. cohort study.

Young women who were obese had a nearly twofold increase in risk of early-onset colorectal cancer, compared with women of normal weight, authors of the study reported in JAMA Oncology.

The findings suggest body weight could be used to “personalize and complement” early cancer screening strategies among adults younger than 50 years, said investigator Po-Hong Liu, MD, of Washington University, St. Louis, and coauthors.

“Given that most of these younger cases are diagnosed symptomatically with more advanced tumors and with a significant influence on years of life lost, our findings reinforce the benefits of maintaining a healthy weight throughout life,” Dr. Liu and coinvestigators said in their report.

Their analysis was based on the ongoing Nurses Health Study II, which began in 1989 and enrolled a total of 116,430 women between the ages of 25 and 42 years in 14 U.S. states. Women completed questionnaires on demographics, medical and health information, and lifestyle factors every 2 years after enrollment.

Dr. Liu and colleagues were able to document 114 cases of colorectal cancer over a median of 13.9 years of follow-up in 85,256 women who had no cancer or inflammatory bowel disease when they were enrolled in the study. The median age at diagnosis for these cancers was 45 years.

Obesity was independently associated with increased risk of these early-onset colorectal cancers, the investigators found in multivariable analysis.

Women with a body mass index of 30 kg/m² or higher had a relative risk of 1.93 (95% confidence interval, 1.15-3.25) versus women with normal BMIs in the 18.5 to 22.9-kg/m² range, according to results of the analysis, they reported.

There was an apparent linear trend between increasing weight and increasing colorectal cancer risk, they added in their report.

They also found links between BMI in early adulthood and risk of early-onset colorectal cancer, including a relative risk of 1.63 for women who reported a BMI of 23 kg/m² or higher at 18 years of age, versus women with a BMI of 18.5-20.9 kg/m² at that age.

Similarly, increase in weight since early adulthood was associated with increased cancer risk, they reported.

While the link between excess weight and colorectal cancer incidence and mortality is well established in previous studies, this study is one of few reports looking at the association in younger individuals, according to Dr. Liu and colleagues.

This is thought to be the first prospective study looking at the link between obesity and risk of colo-rectal cancer diagnosed before the age of 50, they added.

The study was funded by grants from the National Institutes of Health. Dr. Liu had no conflict of interest disclosures related to the study. One coauthor reported consulting fees from Bayer Pharma AG, Janssen, and Pfizer.

[email protected]

SOURCE: Liu P-H et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4280.

AGA Resource 

Visit the AGA GI Patient Center for education to share with your patients about obesity, colorectal cancer and other GI disorders at patient.gastro.org.

Obesity and weight gain are linked to increased risk of colorectal cancer in younger women, according to an analysis of a large, prospective U.S. cohort study.

Young women who were obese had a nearly twofold increase in risk of early-onset colorectal cancer, compared with women of normal weight, authors of the study reported in JAMA Oncology.

The findings suggest body weight could be used to “personalize and complement” early cancer screening strategies among adults younger than 50 years, said investigator Po-Hong Liu, MD, of Washington University, St. Louis, and coauthors.

“Given that most of these younger cases are diagnosed symptomatically with more advanced tumors and with a significant influence on years of life lost, our findings reinforce the benefits of maintaining a healthy weight throughout life,” Dr. Liu and coinvestigators said in their report.

Their analysis was based on the ongoing Nurses Health Study II, which began in 1989 and enrolled a total of 116,430 women between the ages of 25 and 42 years in 14 U.S. states. Women completed questionnaires on demographics, medical and health information, and lifestyle factors every 2 years after enrollment.

Dr. Liu and colleagues were able to document 114 cases of colorectal cancer over a median of 13.9 years of follow-up in 85,256 women who had no cancer or inflammatory bowel disease when they were enrolled in the study. The median age at diagnosis for these cancers was 45 years.

Obesity was independently associated with increased risk of these early-onset colorectal cancers, the investigators found in multivariable analysis.

Women with a body mass index of 30 kg/m² or higher had a relative risk of 1.93 (95% confidence interval, 1.15-3.25) versus women with normal BMIs in the 18.5 to 22.9-kg/m² range, according to results of the analysis, they reported.

There was an apparent linear trend between increasing weight and increasing colorectal cancer risk, they added in their report.

They also found links between BMI in early adulthood and risk of early-onset colorectal cancer, including a relative risk of 1.63 for women who reported a BMI of 23 kg/m² or higher at 18 years of age, versus women with a BMI of 18.5-20.9 kg/m² at that age.

Similarly, increase in weight since early adulthood was associated with increased cancer risk, they reported.

While the link between excess weight and colorectal cancer incidence and mortality is well established in previous studies, this study is one of few reports looking at the association in younger individuals, according to Dr. Liu and colleagues.

This is thought to be the first prospective study looking at the link between obesity and risk of colo-rectal cancer diagnosed before the age of 50, they added.

The study was funded by grants from the National Institutes of Health. Dr. Liu had no conflict of interest disclosures related to the study. One coauthor reported consulting fees from Bayer Pharma AG, Janssen, and Pfizer.

[email protected]

SOURCE: Liu P-H et al. JAMA Oncol. 2018 Oct 11. doi: 10.1001/jamaoncol.2018.4280.

AGA Resource 

Visit the AGA GI Patient Center for education to share with your patients about obesity, colorectal cancer and other GI disorders at patient.gastro.org.

Bortezomib in combination with rituximab plus chemotherapy significantly improved overall survival in transplant-ineligible patients with newly diagnosed mantle cell lymphoma (MCL), compared with standard treatment, according to final results from the international, phase 3 LYM-3002 trial.

Courtesy Wikimedia Commons/Nephron/Creative Commons

After a median follow-up period of 82.0 months, median overall survival was 90.7 months among participants who were given first-line bortezomib in addition to rituximab plus cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus 55.7 months in the control arm, where patients were given rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), for a hazard ratio of 0.66 (95% confidence interval, 0.51-0.85; P = .001).

Tadeusz Robak, MD, of the Medical University of Lodz in Poland, and his colleagues also reported that patients in the bortezomib arm experienced two novel adverse effects, which were different from findings reported in the primary analysis. Each case was classified as grade 4; there was one case of gastric cancer and one case of lung adenocarcinoma.

The findings were reported in the Lancet Oncology.

Among 268 patients in the follow-up analysis set, the median age was 66 years and 31% were classified as high risk based on the MCL-specific International Prognostic Index (MIPI). For those considered high risk, no significant difference was noted when comparing the two groups on the basis of overall survival.

“When analyzed according to MIPI risk category, VR-CAP was associated with significantly improved overall survival, compared with R-CHOP in the low-risk and intermediate-risk categories, but not in the high-risk category,” the investigators wrote.

The authors acknowledged a key limitation of the study was that rituximab was not given as a maintenance therapy since it was not considered standard of care at the time of study initiation.

Moving forward, Dr. Robak and his colleagues recommended that bortezomib be investigated in combination with newer targeted therapies in order to establish best practice for treating MCL.

The study was sponsored by Janssen Pharmaceuticals. The authors reported financial ties to Janssen, Celgene, Ipsen Biopharmaceuticals, Johnson & Johnson, Novartis, and others.

SOURCE: Robak T et al. Lancet Oncol. 2018 Oct 19. doi: 10.1016/S1470-2045(18)30685-5.

Bortezomib in combination with rituximab plus chemotherapy significantly improved overall survival in transplant-ineligible patients with newly diagnosed mantle cell lymphoma (MCL), compared with standard treatment, according to final results from the international, phase 3 LYM-3002 trial.

Courtesy Wikimedia Commons/Nephron/Creative Commons

After a median follow-up period of 82.0 months, median overall survival was 90.7 months among participants who were given first-line bortezomib in addition to rituximab plus cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus 55.7 months in the control arm, where patients were given rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), for a hazard ratio of 0.66 (95% confidence interval, 0.51-0.85; P = .001).

Tadeusz Robak, MD, of the Medical University of Lodz in Poland, and his colleagues also reported that patients in the bortezomib arm experienced two novel adverse effects, which were different from findings reported in the primary analysis. Each case was classified as grade 4; there was one case of gastric cancer and one case of lung adenocarcinoma.

The findings were reported in the Lancet Oncology.

Among 268 patients in the follow-up analysis set, the median age was 66 years and 31% were classified as high risk based on the MCL-specific International Prognostic Index (MIPI). For those considered high risk, no significant difference was noted when comparing the two groups on the basis of overall survival.

“When analyzed according to MIPI risk category, VR-CAP was associated with significantly improved overall survival, compared with R-CHOP in the low-risk and intermediate-risk categories, but not in the high-risk category,” the investigators wrote.

The authors acknowledged a key limitation of the study was that rituximab was not given as a maintenance therapy since it was not considered standard of care at the time of study initiation.

Moving forward, Dr. Robak and his colleagues recommended that bortezomib be investigated in combination with newer targeted therapies in order to establish best practice for treating MCL.

The study was sponsored by Janssen Pharmaceuticals. The authors reported financial ties to Janssen, Celgene, Ipsen Biopharmaceuticals, Johnson & Johnson, Novartis, and others.

SOURCE: Robak T et al. Lancet Oncol. 2018 Oct 19. doi: 10.1016/S1470-2045(18)30685-5.

Bortezomib in combination with rituximab plus chemotherapy significantly improved overall survival in transplant-ineligible patients with newly diagnosed mantle cell lymphoma (MCL), compared with standard treatment, according to final results from the international, phase 3 LYM-3002 trial.

Courtesy Wikimedia Commons/Nephron/Creative Commons

After a median follow-up period of 82.0 months, median overall survival was 90.7 months among participants who were given first-line bortezomib in addition to rituximab plus cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus 55.7 months in the control arm, where patients were given rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), for a hazard ratio of 0.66 (95% confidence interval, 0.51-0.85; P = .001).

Tadeusz Robak, MD, of the Medical University of Lodz in Poland, and his colleagues also reported that patients in the bortezomib arm experienced two novel adverse effects, which were different from findings reported in the primary analysis. Each case was classified as grade 4; there was one case of gastric cancer and one case of lung adenocarcinoma.

The findings were reported in the Lancet Oncology.

Among 268 patients in the follow-up analysis set, the median age was 66 years and 31% were classified as high risk based on the MCL-specific International Prognostic Index (MIPI). For those considered high risk, no significant difference was noted when comparing the two groups on the basis of overall survival.

“When analyzed according to MIPI risk category, VR-CAP was associated with significantly improved overall survival, compared with R-CHOP in the low-risk and intermediate-risk categories, but not in the high-risk category,” the investigators wrote.

The authors acknowledged a key limitation of the study was that rituximab was not given as a maintenance therapy since it was not considered standard of care at the time of study initiation.

Moving forward, Dr. Robak and his colleagues recommended that bortezomib be investigated in combination with newer targeted therapies in order to establish best practice for treating MCL.

The study was sponsored by Janssen Pharmaceuticals. The authors reported financial ties to Janssen, Celgene, Ipsen Biopharmaceuticals, Johnson & Johnson, Novartis, and others.

SOURCE: Robak T et al. Lancet Oncol. 2018 Oct 19. doi: 10.1016/S1470-2045(18)30685-5.

For previously untreated patients with BRAF wild-type advanced melanoma, the antiprogrammed death-ligand 1 agent nivolumab dramatically improved overall survival (OS), compared with standard first-line chemotherapy, according to new data from the CheckMate 066 trial.

At the 3-year follow-up, more than twice as many nivolumab-treated patients were alive, compared with those who received dacarbazine, reported lead author Paolo A. Ascierto, MD, director of the unit of melanoma, cancer immunotherapy, and innovative therapy at the Istituto Nazionale Tumori Fondazione Pascale in Naples, Italy, and his colleagues. Longer median progression-free survival (PFS) and higher complete response rates were also reported.

“The results of this 3-year follow-up analysis provided evidence for a durable survival benefit with nivolumab monotherapy in patients with previously untreated BRAF wild-type advanced melanoma,” the investigators wrote in JAMA Oncology.

The double-blind, phase 3 trial involved 418 patients with unresectable, previously untreated stage III or IV melanoma not exhibiting a BRAF mutation. Patients were randomized to receive either nivolumab (n = 210; 3 mg/kg every 2 weeks plus placebo every 3 weeks) or dacarbazine (n = 208; 1,000 mg/m2 every 3 weeks plus placebo every 2 weeks). Treatment continued until unacceptable toxicity or disease progression occurred.

The results showed dramatic benefits, measured by OS and PFS, when patients were treated with nivolumab. The 3-year OS rate was 51.2% in the nivolumab group, compared with 21.6% in the dacarbazine group, an approximate 130% difference. Median OS and median PFS were also multiplied by the checkpoint inhibitor, showing 230% and 130% improvements, respectively (OS, 37.5 months vs. 11.2 months; PFS, 5.1 months vs. 2.2 months; P less than .001). Grade 3 or higher treatment-related adverse events (AEs) were comparable between treatment arms (nivolumab, 15.0% vs. dacarbazine, 17.6%).

“Responses to nivolumab were long lasting in many patients who discontinued treatment, with most patients who stopped treatment still alive and without disease progression at the time of the last assessment,” the investigators wrote.

“Collectively, our results showed durable responses and long-term survival with nivolumab monotherapy, with no new AEs developing at late time points,” they concluded.

The study was funded by Bristol-Myers Squibb. The authors reported financial relationships with Bristol-Myers Squibb, Roche/Genentech, Novartis, Amgen, and others.

SOURCE: Ascierto PA et al. JAMA Oncol. 2018 Oct 25. doi: 10.1001/jamaoncol.2018.4514.

For previously untreated patients with BRAF wild-type advanced melanoma, the antiprogrammed death-ligand 1 agent nivolumab dramatically improved overall survival (OS), compared with standard first-line chemotherapy, according to new data from the CheckMate 066 trial.

At the 3-year follow-up, more than twice as many nivolumab-treated patients were alive, compared with those who received dacarbazine, reported lead author Paolo A. Ascierto, MD, director of the unit of melanoma, cancer immunotherapy, and innovative therapy at the Istituto Nazionale Tumori Fondazione Pascale in Naples, Italy, and his colleagues. Longer median progression-free survival (PFS) and higher complete response rates were also reported.

“The results of this 3-year follow-up analysis provided evidence for a durable survival benefit with nivolumab monotherapy in patients with previously untreated BRAF wild-type advanced melanoma,” the investigators wrote in JAMA Oncology.

The double-blind, phase 3 trial involved 418 patients with unresectable, previously untreated stage III or IV melanoma not exhibiting a BRAF mutation. Patients were randomized to receive either nivolumab (n = 210; 3 mg/kg every 2 weeks plus placebo every 3 weeks) or dacarbazine (n = 208; 1,000 mg/m2 every 3 weeks plus placebo every 2 weeks). Treatment continued until unacceptable toxicity or disease progression occurred.

The results showed dramatic benefits, measured by OS and PFS, when patients were treated with nivolumab. The 3-year OS rate was 51.2% in the nivolumab group, compared with 21.6% in the dacarbazine group, an approximate 130% difference. Median OS and median PFS were also multiplied by the checkpoint inhibitor, showing 230% and 130% improvements, respectively (OS, 37.5 months vs. 11.2 months; PFS, 5.1 months vs. 2.2 months; P less than .001). Grade 3 or higher treatment-related adverse events (AEs) were comparable between treatment arms (nivolumab, 15.0% vs. dacarbazine, 17.6%).

“Responses to nivolumab were long lasting in many patients who discontinued treatment, with most patients who stopped treatment still alive and without disease progression at the time of the last assessment,” the investigators wrote.

“Collectively, our results showed durable responses and long-term survival with nivolumab monotherapy, with no new AEs developing at late time points,” they concluded.

The study was funded by Bristol-Myers Squibb. The authors reported financial relationships with Bristol-Myers Squibb, Roche/Genentech, Novartis, Amgen, and others.

SOURCE: Ascierto PA et al. JAMA Oncol. 2018 Oct 25. doi: 10.1001/jamaoncol.2018.4514.

For previously untreated patients with BRAF wild-type advanced melanoma, the antiprogrammed death-ligand 1 agent nivolumab dramatically improved overall survival (OS), compared with standard first-line chemotherapy, according to new data from the CheckMate 066 trial.

At the 3-year follow-up, more than twice as many nivolumab-treated patients were alive, compared with those who received dacarbazine, reported lead author Paolo A. Ascierto, MD, director of the unit of melanoma, cancer immunotherapy, and innovative therapy at the Istituto Nazionale Tumori Fondazione Pascale in Naples, Italy, and his colleagues. Longer median progression-free survival (PFS) and higher complete response rates were also reported.

“The results of this 3-year follow-up analysis provided evidence for a durable survival benefit with nivolumab monotherapy in patients with previously untreated BRAF wild-type advanced melanoma,” the investigators wrote in JAMA Oncology.

The double-blind, phase 3 trial involved 418 patients with unresectable, previously untreated stage III or IV melanoma not exhibiting a BRAF mutation. Patients were randomized to receive either nivolumab (n = 210; 3 mg/kg every 2 weeks plus placebo every 3 weeks) or dacarbazine (n = 208; 1,000 mg/m2 every 3 weeks plus placebo every 2 weeks). Treatment continued until unacceptable toxicity or disease progression occurred.

The results showed dramatic benefits, measured by OS and PFS, when patients were treated with nivolumab. The 3-year OS rate was 51.2% in the nivolumab group, compared with 21.6% in the dacarbazine group, an approximate 130% difference. Median OS and median PFS were also multiplied by the checkpoint inhibitor, showing 230% and 130% improvements, respectively (OS, 37.5 months vs. 11.2 months; PFS, 5.1 months vs. 2.2 months; P less than .001). Grade 3 or higher treatment-related adverse events (AEs) were comparable between treatment arms (nivolumab, 15.0% vs. dacarbazine, 17.6%).

“Responses to nivolumab were long lasting in many patients who discontinued treatment, with most patients who stopped treatment still alive and without disease progression at the time of the last assessment,” the investigators wrote.

“Collectively, our results showed durable responses and long-term survival with nivolumab monotherapy, with no new AEs developing at late time points,” they concluded.

The study was funded by Bristol-Myers Squibb. The authors reported financial relationships with Bristol-Myers Squibb, Roche/Genentech, Novartis, Amgen, and others.

SOURCE: Ascierto PA et al. JAMA Oncol. 2018 Oct 25. doi: 10.1001/jamaoncol.2018.4514.

CHICAGO – Results of the landmark PEXIVAS study – far and away the largest randomized trial ever done in ANCA-associated vasculitis – will likely change treatment in a couple of major ways.

Bruce Jancin/MDedge News

“I think this trial will have an impact on care. Based on these findings, physicians should strongly reconsider the utility of plasma exchange as a treatment for AAV [antineutrophil cytoplasmic antibody–associated vasculitis] patients and should now consider using lower cumulative doses of glucocorticoids for the treatment of severe AAV,” PEXIVAS coprincipal investigator Peter A. Merkel, MD, said at the annual meeting of the American College of Rheumatology.

That’s because the trial demonstrated that plasma exchange neither saved lives nor avoided end-stage renal disease, while utilization of oral glucocorticoids in doses substantially lower than the high-dose current standard significantly reduced the serious infection rate without causing less effective disease control, according to Dr. Merkel, chief of rheumatology and professor of medicine and epidemiology at the University of Pennsylvania in Philadelphia.

PEXIVAS comprised 704 patients with severe granulomatosis with polyangiitis or microscopic polyangiitis, making it more than twice as large as any other trial in AAV. This was a multicenter, international, open-label, randomized trial with a 2-by-2 factorial design. To qualify as having severe AAV, participants had to have an estimated glomerular filtration rate below 50 mL/min per 1.73 m² and/or lung hemorrhage.

“This was in essence two trials embedded within one protocol in the factorial design,” he explained.

The impetus for this major clinical trial was a recognition that mortality due to AAV remains high, especially in the first year, with a clear unmet need for better, less toxic therapies. Indeed, it’s estimated that only 29% of deaths in the first year after diagnosis are due to the vasculitis disease itself, while over 50% of the mortality is caused by infection, much of it collateral damage from immunosuppressive therapies.

Dr. Merkel, who heads the National Institutes of Health–supported Vasculitis Clinical Research Consortium, said the time was right for a clinical trial aimed at improving patient management: “Clinical equipoise exists for the efficacy of both plasma exchange and reduced-dose glucocorticoids in ANCA-associated vasculitis.”

The patients underwent induction therapy with cyclophosphamide or rituximab (Rituxan) plus IV methylprednisolone. Then they were randomized to seven plasma exchange sessions in 14 days or no plasma exchange, and further randomized to conventional weight-based, high-dose oral glucocorticoids or a lower-dose regimen. Those on the reduced-dose regimen received 54% of the cumulative amount of glucocorticoids used in the standard-dose group through the first 3 months, and 61% over the course of 6 months. By week 4, those on the reduced-dose regimen were on an average of 25 mg/day, while those on standard therapy were on 50 mg/day. Adherence to assigned study arms exceeded 90%. Patients were followed prospectively for 1-7 years.

The primary endpoint, a composite of all-cause mortality or development of end-stage renal disease, occurred in 28% of patients on plasma exchange and 31% of those who did not undergo plasma exchange, a nonsignificant difference indicative of a lack of benefit for the intervention. No differential effect was seen in prespecified subgroups based on age, creatinine clearance, ANCA type, form of immunosuppression, or presence or absence of lung hemorrhage.

Further, the primary endpoint occurred in 28% of patients on reduced-dose glucocorticoids, compared with 26% on full-dose therapy; again, a nonsignificant difference, meaning lower-dose therapy didn’t result in less effective disease control. But it did result in a significant reduction in the prespecified endpoint of serious infections in the first year: 27% versus 33% with full-dose therapy, representing a 30% relative risk reduction.

Audience members wanted to know if there are any circumstances at all in which Dr. Merkel would now consider resorting to plasma exchange, such as maybe in AAV patients at the most extreme end of the severity spectrum.

“I’m not sure I should be the one dictating that; I think the world needs to see the data,” he replied.

That being said, he added, “I think these data are incredibly helpful to physicians and patients as they face this decision. I think plasma exchange is an expensive therapy and somewhat invasive. I think our results indicate that the benefit that we may have thought was there is not there.”

The study was sponsored by the National Institutes of Health, the Food and Drug Administration, the U.K. Medical Research Council and the National Institute for Health Research, the Canadian Institutes of Health Research, and the governments of France, Australia, and New Zealand. The presenter reported receiving research funding from the ACR, EULAR, FDA, NIH, Patient-Centered Outcomes Research Institute, and the Vasculitis Foundation. He also receives research funding from and/or serves as a consultant to more than a dozen pharmaceutical companies.

[email protected]

SOURCE: Merkel PA et al. Arthritis Rheumatol. 2018;70(Suppl 10):Abstract 2788.

CHICAGO – Results of the landmark PEXIVAS study – far and away the largest randomized trial ever done in ANCA-associated vasculitis – will likely change treatment in a couple of major ways.

Bruce Jancin/MDedge News

“I think this trial will have an impact on care. Based on these findings, physicians should strongly reconsider the utility of plasma exchange as a treatment for AAV [antineutrophil cytoplasmic antibody–associated vasculitis] patients and should now consider using lower cumulative doses of glucocorticoids for the treatment of severe AAV,” PEXIVAS coprincipal investigator Peter A. Merkel, MD, said at the annual meeting of the American College of Rheumatology.

That’s because the trial demonstrated that plasma exchange neither saved lives nor avoided end-stage renal disease, while utilization of oral glucocorticoids in doses substantially lower than the high-dose current standard significantly reduced the serious infection rate without causing less effective disease control, according to Dr. Merkel, chief of rheumatology and professor of medicine and epidemiology at the University of Pennsylvania in Philadelphia.

PEXIVAS comprised 704 patients with severe granulomatosis with polyangiitis or microscopic polyangiitis, making it more than twice as large as any other trial in AAV. This was a multicenter, international, open-label, randomized trial with a 2-by-2 factorial design. To qualify as having severe AAV, participants had to have an estimated glomerular filtration rate below 50 mL/min per 1.73 m² and/or lung hemorrhage.

“This was in essence two trials embedded within one protocol in the factorial design,” he explained.

The impetus for this major clinical trial was a recognition that mortality due to AAV remains high, especially in the first year, with a clear unmet need for better, less toxic therapies. Indeed, it’s estimated that only 29% of deaths in the first year after diagnosis are due to the vasculitis disease itself, while over 50% of the mortality is caused by infection, much of it collateral damage from immunosuppressive therapies.

Dr. Merkel, who heads the National Institutes of Health–supported Vasculitis Clinical Research Consortium, said the time was right for a clinical trial aimed at improving patient management: “Clinical equipoise exists for the efficacy of both plasma exchange and reduced-dose glucocorticoids in ANCA-associated vasculitis.”

The patients underwent induction therapy with cyclophosphamide or rituximab (Rituxan) plus IV methylprednisolone. Then they were randomized to seven plasma exchange sessions in 14 days or no plasma exchange, and further randomized to conventional weight-based, high-dose oral glucocorticoids or a lower-dose regimen. Those on the reduced-dose regimen received 54% of the cumulative amount of glucocorticoids used in the standard-dose group through the first 3 months, and 61% over the course of 6 months. By week 4, those on the reduced-dose regimen were on an average of 25 mg/day, while those on standard therapy were on 50 mg/day. Adherence to assigned study arms exceeded 90%. Patients were followed prospectively for 1-7 years.

The primary endpoint, a composite of all-cause mortality or development of end-stage renal disease, occurred in 28% of patients on plasma exchange and 31% of those who did not undergo plasma exchange, a nonsignificant difference indicative of a lack of benefit for the intervention. No differential effect was seen in prespecified subgroups based on age, creatinine clearance, ANCA type, form of immunosuppression, or presence or absence of lung hemorrhage.

Further, the primary endpoint occurred in 28% of patients on reduced-dose glucocorticoids, compared with 26% on full-dose therapy; again, a nonsignificant difference, meaning lower-dose therapy didn’t result in less effective disease control. But it did result in a significant reduction in the prespecified endpoint of serious infections in the first year: 27% versus 33% with full-dose therapy, representing a 30% relative risk reduction.

Audience members wanted to know if there are any circumstances at all in which Dr. Merkel would now consider resorting to plasma exchange, such as maybe in AAV patients at the most extreme end of the severity spectrum.

“I’m not sure I should be the one dictating that; I think the world needs to see the data,” he replied.

That being said, he added, “I think these data are incredibly helpful to physicians and patients as they face this decision. I think plasma exchange is an expensive therapy and somewhat invasive. I think our results indicate that the benefit that we may have thought was there is not there.”

The study was sponsored by the National Institutes of Health, the Food and Drug Administration, the U.K. Medical Research Council and the National Institute for Health Research, the Canadian Institutes of Health Research, and the governments of France, Australia, and New Zealand. The presenter reported receiving research funding from the ACR, EULAR, FDA, NIH, Patient-Centered Outcomes Research Institute, and the Vasculitis Foundation. He also receives research funding from and/or serves as a consultant to more than a dozen pharmaceutical companies.

[email protected]

SOURCE: Merkel PA et al. Arthritis Rheumatol. 2018;70(Suppl 10):Abstract 2788.

CHICAGO – Results of the landmark PEXIVAS study – far and away the largest randomized trial ever done in ANCA-associated vasculitis – will likely change treatment in a couple of major ways.

Bruce Jancin/MDedge News

“I think this trial will have an impact on care. Based on these findings, physicians should strongly reconsider the utility of plasma exchange as a treatment for AAV [antineutrophil cytoplasmic antibody–associated vasculitis] patients and should now consider using lower cumulative doses of glucocorticoids for the treatment of severe AAV,” PEXIVAS coprincipal investigator Peter A. Merkel, MD, said at the annual meeting of the American College of Rheumatology.

That’s because the trial demonstrated that plasma exchange neither saved lives nor avoided end-stage renal disease, while utilization of oral glucocorticoids in doses substantially lower than the high-dose current standard significantly reduced the serious infection rate without causing less effective disease control, according to Dr. Merkel, chief of rheumatology and professor of medicine and epidemiology at the University of Pennsylvania in Philadelphia.

PEXIVAS comprised 704 patients with severe granulomatosis with polyangiitis or microscopic polyangiitis, making it more than twice as large as any other trial in AAV. This was a multicenter, international, open-label, randomized trial with a 2-by-2 factorial design. To qualify as having severe AAV, participants had to have an estimated glomerular filtration rate below 50 mL/min per 1.73 m² and/or lung hemorrhage.

“This was in essence two trials embedded within one protocol in the factorial design,” he explained.

The impetus for this major clinical trial was a recognition that mortality due to AAV remains high, especially in the first year, with a clear unmet need for better, less toxic therapies. Indeed, it’s estimated that only 29% of deaths in the first year after diagnosis are due to the vasculitis disease itself, while over 50% of the mortality is caused by infection, much of it collateral damage from immunosuppressive therapies.

Dr. Merkel, who heads the National Institutes of Health–supported Vasculitis Clinical Research Consortium, said the time was right for a clinical trial aimed at improving patient management: “Clinical equipoise exists for the efficacy of both plasma exchange and reduced-dose glucocorticoids in ANCA-associated vasculitis.”

The patients underwent induction therapy with cyclophosphamide or rituximab (Rituxan) plus IV methylprednisolone. Then they were randomized to seven plasma exchange sessions in 14 days or no plasma exchange, and further randomized to conventional weight-based, high-dose oral glucocorticoids or a lower-dose regimen. Those on the reduced-dose regimen received 54% of the cumulative amount of glucocorticoids used in the standard-dose group through the first 3 months, and 61% over the course of 6 months. By week 4, those on the reduced-dose regimen were on an average of 25 mg/day, while those on standard therapy were on 50 mg/day. Adherence to assigned study arms exceeded 90%. Patients were followed prospectively for 1-7 years.

The primary endpoint, a composite of all-cause mortality or development of end-stage renal disease, occurred in 28% of patients on plasma exchange and 31% of those who did not undergo plasma exchange, a nonsignificant difference indicative of a lack of benefit for the intervention. No differential effect was seen in prespecified subgroups based on age, creatinine clearance, ANCA type, form of immunosuppression, or presence or absence of lung hemorrhage.

Further, the primary endpoint occurred in 28% of patients on reduced-dose glucocorticoids, compared with 26% on full-dose therapy; again, a nonsignificant difference, meaning lower-dose therapy didn’t result in less effective disease control. But it did result in a significant reduction in the prespecified endpoint of serious infections in the first year: 27% versus 33% with full-dose therapy, representing a 30% relative risk reduction.

Audience members wanted to know if there are any circumstances at all in which Dr. Merkel would now consider resorting to plasma exchange, such as maybe in AAV patients at the most extreme end of the severity spectrum.

“I’m not sure I should be the one dictating that; I think the world needs to see the data,” he replied.

That being said, he added, “I think these data are incredibly helpful to physicians and patients as they face this decision. I think plasma exchange is an expensive therapy and somewhat invasive. I think our results indicate that the benefit that we may have thought was there is not there.”

The study was sponsored by the National Institutes of Health, the Food and Drug Administration, the U.K. Medical Research Council and the National Institute for Health Research, the Canadian Institutes of Health Research, and the governments of France, Australia, and New Zealand. The presenter reported receiving research funding from the ACR, EULAR, FDA, NIH, Patient-Centered Outcomes Research Institute, and the Vasculitis Foundation. He also receives research funding from and/or serves as a consultant to more than a dozen pharmaceutical companies.

[email protected]

SOURCE: Merkel PA et al. Arthritis Rheumatol. 2018;70(Suppl 10):Abstract 2788.

On Sept. 14, AGA held Advocacy Day. This was a day in which several AGA members met with staff of Congressional representatives on Capitol Hill to advocate for important issues within the field of gastroenterology. The three primary issues involved:

• Support of increased NIH funding.
• Requesting increased transparency in insurance-driven step-therapy protocols.
• Removal of the coinsurance or copayment for screening colonoscopies that become therapeutic, once polyps are identified and removed.

These issues support growth and autonomy of our field, while supporting the interests of our patients.

Advocacy is not difficult. Many of my fellow GIs are unnecessarily intimidated by this word; however, each individual has the ability and, arguably, the responsibility to shape the environment in which we practice. Opportunities to engage your representatives may be as simple as clicking a link, leaving a voicemail, or signing a petition, to testifying at hearings or hosting a representative at your own institution. AGA staff made participating in Advocacy Day very easy. Staff at AGA coordinate meetings between each advocate, and the offices of his or her local Congress members. AGA also provides brief training prior to these meetings; thus, no prior experience is required. I felt well prepared for the meetings with my local Congress staff members.

I chose to participate in Advocacy Day because I want to bring the experiences of my colleagues and patients to the doorsteps of those who make decisions about how we practice. I feel that it is important to stand up for our field and our patients, lest others make decisions for us. We do not have to feel powerless in a changing field. Let your voice be heard.

Dr. Anjou is a gastroenterologist at the University of Connecticut Health Center, Farmington, and member of the AGA Trainee and Early Career Committee and Quality Measures Committee.

On Sept. 14, AGA held Advocacy Day. This was a day in which several AGA members met with staff of Congressional representatives on Capitol Hill to advocate for important issues within the field of gastroenterology. The three primary issues involved:

• Support of increased NIH funding.
• Requesting increased transparency in insurance-driven step-therapy protocols.
• Removal of the coinsurance or copayment for screening colonoscopies that become therapeutic, once polyps are identified and removed.

These issues support growth and autonomy of our field, while supporting the interests of our patients.

Advocacy is not difficult. Many of my fellow GIs are unnecessarily intimidated by this word; however, each individual has the ability and, arguably, the responsibility to shape the environment in which we practice. Opportunities to engage your representatives may be as simple as clicking a link, leaving a voicemail, or signing a petition, to testifying at hearings or hosting a representative at your own institution. AGA staff made participating in Advocacy Day very easy. Staff at AGA coordinate meetings between each advocate, and the offices of his or her local Congress members. AGA also provides brief training prior to these meetings; thus, no prior experience is required. I felt well prepared for the meetings with my local Congress staff members.

I chose to participate in Advocacy Day because I want to bring the experiences of my colleagues and patients to the doorsteps of those who make decisions about how we practice. I feel that it is important to stand up for our field and our patients, lest others make decisions for us. We do not have to feel powerless in a changing field. Let your voice be heard.

Dr. Anjou is a gastroenterologist at the University of Connecticut Health Center, Farmington, and member of the AGA Trainee and Early Career Committee and Quality Measures Committee.

On Sept. 14, AGA held Advocacy Day. This was a day in which several AGA members met with staff of Congressional representatives on Capitol Hill to advocate for important issues within the field of gastroenterology. The three primary issues involved:

• Support of increased NIH funding.
• Requesting increased transparency in insurance-driven step-therapy protocols.
• Removal of the coinsurance or copayment for screening colonoscopies that become therapeutic, once polyps are identified and removed.

These issues support growth and autonomy of our field, while supporting the interests of our patients.

Advocacy is not difficult. Many of my fellow GIs are unnecessarily intimidated by this word; however, each individual has the ability and, arguably, the responsibility to shape the environment in which we practice. Opportunities to engage your representatives may be as simple as clicking a link, leaving a voicemail, or signing a petition, to testifying at hearings or hosting a representative at your own institution. AGA staff made participating in Advocacy Day very easy. Staff at AGA coordinate meetings between each advocate, and the offices of his or her local Congress members. AGA also provides brief training prior to these meetings; thus, no prior experience is required. I felt well prepared for the meetings with my local Congress staff members.

I chose to participate in Advocacy Day because I want to bring the experiences of my colleagues and patients to the doorsteps of those who make decisions about how we practice. I feel that it is important to stand up for our field and our patients, lest others make decisions for us. We do not have to feel powerless in a changing field. Let your voice be heard.

Dr. Anjou is a gastroenterologist at the University of Connecticut Health Center, Farmington, and member of the AGA Trainee and Early Career Committee and Quality Measures Committee.

CHICAGO – Drafts of new classification criteria for giant cell arteritis and Takayasu’s arteritis developed by the American College of Rheumatology and the European League Against Rheumatism (EULAR) reflect the increasingly important role of advanced vascular imaging in the diagnosis and management of large-vessel vasculitis, according to Peter A. Merkel, MD.
 

The drafts, which are the result of a multiyear collaboration between the ACR and EULAR, were presented at the annual meeting of the ACR and will be submitted to the ACR/EULAR committee overseeing the work for comprehensive review and possible revisions. Once endorsed, the new criteria will replace the “extremely important,” but outdated, existing classification criteria, which were published in 1990.

“What we’ve done is, rather than purely revise the 1990 [criteria], we’ve started again from scratch ... with a great number of cases from a wide variety of centers throughout the world. This was a very large international effort ... really a great community effort in the field of rheumatology,” Dr. Merkel, professor and chief of the division of rheumatology at the University of Pennsylvania, Philadelphia, and one of the chief investigators for the project, said in a video interview.

The new criteria will allow for better classification of patients with giant cell arteritis versus Takayasu’s arteritis versus another form of vasculitis, he said, noting that advances in imaging that allow for “more enriched data with which to make decisions” play a large role.

However, the new criteria are not meant to be used for diagnosis, but to “sort out among the different types of vasculitis,” he said.

“It provides awareness and it provides a tool, especially for research investigation, but that seeps out into the broader community,” he added.

Dr. Merkel reported having no disclosures.

[email protected]

SOURCE: Merkel PA et al. ACR Annual Meeting, Presentation 5T116.

CHICAGO – Drafts of new classification criteria for giant cell arteritis and Takayasu’s arteritis developed by the American College of Rheumatology and the European League Against Rheumatism (EULAR) reflect the increasingly important role of advanced vascular imaging in the diagnosis and management of large-vessel vasculitis, according to Peter A. Merkel, MD.
 

The drafts, which are the result of a multiyear collaboration between the ACR and EULAR, were presented at the annual meeting of the ACR and will be submitted to the ACR/EULAR committee overseeing the work for comprehensive review and possible revisions. Once endorsed, the new criteria will replace the “extremely important,” but outdated, existing classification criteria, which were published in 1990.

“What we’ve done is, rather than purely revise the 1990 [criteria], we’ve started again from scratch ... with a great number of cases from a wide variety of centers throughout the world. This was a very large international effort ... really a great community effort in the field of rheumatology,” Dr. Merkel, professor and chief of the division of rheumatology at the University of Pennsylvania, Philadelphia, and one of the chief investigators for the project, said in a video interview.

The new criteria will allow for better classification of patients with giant cell arteritis versus Takayasu’s arteritis versus another form of vasculitis, he said, noting that advances in imaging that allow for “more enriched data with which to make decisions” play a large role.

However, the new criteria are not meant to be used for diagnosis, but to “sort out among the different types of vasculitis,” he said.

“It provides awareness and it provides a tool, especially for research investigation, but that seeps out into the broader community,” he added.

Dr. Merkel reported having no disclosures.

[email protected]

SOURCE: Merkel PA et al. ACR Annual Meeting, Presentation 5T116.

CHICAGO – Drafts of new classification criteria for giant cell arteritis and Takayasu’s arteritis developed by the American College of Rheumatology and the European League Against Rheumatism (EULAR) reflect the increasingly important role of advanced vascular imaging in the diagnosis and management of large-vessel vasculitis, according to Peter A. Merkel, MD.
 

The drafts, which are the result of a multiyear collaboration between the ACR and EULAR, were presented at the annual meeting of the ACR and will be submitted to the ACR/EULAR committee overseeing the work for comprehensive review and possible revisions. Once endorsed, the new criteria will replace the “extremely important,” but outdated, existing classification criteria, which were published in 1990.

“What we’ve done is, rather than purely revise the 1990 [criteria], we’ve started again from scratch ... with a great number of cases from a wide variety of centers throughout the world. This was a very large international effort ... really a great community effort in the field of rheumatology,” Dr. Merkel, professor and chief of the division of rheumatology at the University of Pennsylvania, Philadelphia, and one of the chief investigators for the project, said in a video interview.

The new criteria will allow for better classification of patients with giant cell arteritis versus Takayasu’s arteritis versus another form of vasculitis, he said, noting that advances in imaging that allow for “more enriched data with which to make decisions” play a large role.

However, the new criteria are not meant to be used for diagnosis, but to “sort out among the different types of vasculitis,” he said.

“It provides awareness and it provides a tool, especially for research investigation, but that seeps out into the broader community,” he added.

Dr. Merkel reported having no disclosures.

[email protected]

SOURCE: Merkel PA et al. ACR Annual Meeting, Presentation 5T116.