There has been little to no recent improvement in the large share of cancer patients who are not receiving detailed information about survivorship care, suggests a nationally representative cross-sectional survey.

In 2006, the Institute of Medicine issued a seminal report recommending survivorship care planning to address the special needs of this patient population, noted the investigators, led by Ashish Rai, PhD, American Cancer Society, Framingham, Mass. Other organizations have since issued guidelines and policies in this area.

For the study, Dr. Rai and colleagues analyzed data from 2,266 survivors who completed the 2011 or 2016 Medical Expenditure Panel Survey – Experiences with Cancer questionnaire. Survivors were asked whether any clinician had ever discussed various aspects of survivorship care; responses were dichotomized as having had detailed discussion versus not (brief or no discussion, or not remembering).

Between 2011 and 2016, there was minimal change in the percentage of survivors who reported not receiving detailed information on follow-up care (from 35.1% to 35.4%), late or long-term adverse effects (from 54.2% to 55.5%), lifestyle recommendations (from 58.9% to 57.8%), and emotional or social needs (from 69.2% to 68.2%), the investigators wrote. Their report is in Journal of Oncology Practice.

When analyses were restricted to only those survivors who had received cancer-directed treatment within 3 years of the survey, findings were essentially the same.

About one-quarter of survivors reported having detailed discussions about all four topics in both 2011 (24.4%) and 2016 (21.9%).

In 2016, nearly half of survivors, 47.6%, reported not having detailed discussions with their providers about a summary of their cancer treatments. (This question was not asked in 2011.)

“Despite national efforts and organizations promoting survivorship care planning and highlighting the need for improved quality of survivorship care delivery, clear gaps in quality of communication between survivors of cancer and providers persist,” Dr. Rai and colleagues said.

“Continued efforts are needed to promote communication about survivorship issues, including implementation and evaluation of targeted interventions in key survivorship care areas,” they recommended. “These interventions may consist of furnishing guidance on optimal ways to identify and address survivors’ communication needs, streamlining the flow of information across provider types, ensuring better integration of primary care providers with the survivorship care paradigm, and augmenting the use of health information technology for collection and dissemination of information across the cancer control continuum.”

Dr. Rai did not disclose any relevant conflicts of interest. The study did not receive specific funding.

SOURCE: Rai A et al. J Oncol Pract. 2019 July 2. doi: 10.1200/JOP.19.00157.

There has been little to no recent improvement in the large share of cancer patients who are not receiving detailed information about survivorship care, suggests a nationally representative cross-sectional survey.

In 2006, the Institute of Medicine issued a seminal report recommending survivorship care planning to address the special needs of this patient population, noted the investigators, led by Ashish Rai, PhD, American Cancer Society, Framingham, Mass. Other organizations have since issued guidelines and policies in this area.

For the study, Dr. Rai and colleagues analyzed data from 2,266 survivors who completed the 2011 or 2016 Medical Expenditure Panel Survey – Experiences with Cancer questionnaire. Survivors were asked whether any clinician had ever discussed various aspects of survivorship care; responses were dichotomized as having had detailed discussion versus not (brief or no discussion, or not remembering).

Between 2011 and 2016, there was minimal change in the percentage of survivors who reported not receiving detailed information on follow-up care (from 35.1% to 35.4%), late or long-term adverse effects (from 54.2% to 55.5%), lifestyle recommendations (from 58.9% to 57.8%), and emotional or social needs (from 69.2% to 68.2%), the investigators wrote. Their report is in Journal of Oncology Practice.

When analyses were restricted to only those survivors who had received cancer-directed treatment within 3 years of the survey, findings were essentially the same.

About one-quarter of survivors reported having detailed discussions about all four topics in both 2011 (24.4%) and 2016 (21.9%).

In 2016, nearly half of survivors, 47.6%, reported not having detailed discussions with their providers about a summary of their cancer treatments. (This question was not asked in 2011.)

“Despite national efforts and organizations promoting survivorship care planning and highlighting the need for improved quality of survivorship care delivery, clear gaps in quality of communication between survivors of cancer and providers persist,” Dr. Rai and colleagues said.

“Continued efforts are needed to promote communication about survivorship issues, including implementation and evaluation of targeted interventions in key survivorship care areas,” they recommended. “These interventions may consist of furnishing guidance on optimal ways to identify and address survivors’ communication needs, streamlining the flow of information across provider types, ensuring better integration of primary care providers with the survivorship care paradigm, and augmenting the use of health information technology for collection and dissemination of information across the cancer control continuum.”

Dr. Rai did not disclose any relevant conflicts of interest. The study did not receive specific funding.

SOURCE: Rai A et al. J Oncol Pract. 2019 July 2. doi: 10.1200/JOP.19.00157.

There has been little to no recent improvement in the large share of cancer patients who are not receiving detailed information about survivorship care, suggests a nationally representative cross-sectional survey.

In 2006, the Institute of Medicine issued a seminal report recommending survivorship care planning to address the special needs of this patient population, noted the investigators, led by Ashish Rai, PhD, American Cancer Society, Framingham, Mass. Other organizations have since issued guidelines and policies in this area.

For the study, Dr. Rai and colleagues analyzed data from 2,266 survivors who completed the 2011 or 2016 Medical Expenditure Panel Survey – Experiences with Cancer questionnaire. Survivors were asked whether any clinician had ever discussed various aspects of survivorship care; responses were dichotomized as having had detailed discussion versus not (brief or no discussion, or not remembering).

Between 2011 and 2016, there was minimal change in the percentage of survivors who reported not receiving detailed information on follow-up care (from 35.1% to 35.4%), late or long-term adverse effects (from 54.2% to 55.5%), lifestyle recommendations (from 58.9% to 57.8%), and emotional or social needs (from 69.2% to 68.2%), the investigators wrote. Their report is in Journal of Oncology Practice.

When analyses were restricted to only those survivors who had received cancer-directed treatment within 3 years of the survey, findings were essentially the same.

About one-quarter of survivors reported having detailed discussions about all four topics in both 2011 (24.4%) and 2016 (21.9%).

In 2016, nearly half of survivors, 47.6%, reported not having detailed discussions with their providers about a summary of their cancer treatments. (This question was not asked in 2011.)

“Despite national efforts and organizations promoting survivorship care planning and highlighting the need for improved quality of survivorship care delivery, clear gaps in quality of communication between survivors of cancer and providers persist,” Dr. Rai and colleagues said.

“Continued efforts are needed to promote communication about survivorship issues, including implementation and evaluation of targeted interventions in key survivorship care areas,” they recommended. “These interventions may consist of furnishing guidance on optimal ways to identify and address survivors’ communication needs, streamlining the flow of information across provider types, ensuring better integration of primary care providers with the survivorship care paradigm, and augmenting the use of health information technology for collection and dissemination of information across the cancer control continuum.”

Dr. Rai did not disclose any relevant conflicts of interest. The study did not receive specific funding.

SOURCE: Rai A et al. J Oncol Pract. 2019 July 2. doi: 10.1200/JOP.19.00157.

The United States continues to slowly add new cases of measles to 2019’s postelimination-record total, but California was officially removed from the outbreak list this week, according to the Centers for Disease Control and Prevention.

There were 14 new measles cases reported during the week ending July 11, bringing the total for the year to 1,123 in 28 states, the CDC reported July 15. That is the highest number of cases reported since measles was declared eliminated in 2000 and the most in a single year since 1992.

The end of outbreak-related activity in California leaves three locations still dealing with ongoing cases: Rockland County, N.Y.; New York City; and King, Pierce, and Snohomish Counties in Washington, the CDC said.

Those three jurisdictions currently report the following:

• reported four new cases from July 3 to July 11 and is up to 175 cases for the year.
• had one new case from July 1 to July 8 and is now at 564 for the year.
• reported two cases from July 1 to July 10 and is now at 10 for the year (the other two counties have a total of three cases). Clark County in Washington reported 71 cases in an earlier, unrelated outbreak.

[email protected]

The United States continues to slowly add new cases of measles to 2019’s postelimination-record total, but California was officially removed from the outbreak list this week, according to the Centers for Disease Control and Prevention.

There were 14 new measles cases reported during the week ending July 11, bringing the total for the year to 1,123 in 28 states, the CDC reported July 15. That is the highest number of cases reported since measles was declared eliminated in 2000 and the most in a single year since 1992.

The end of outbreak-related activity in California leaves three locations still dealing with ongoing cases: Rockland County, N.Y.; New York City; and King, Pierce, and Snohomish Counties in Washington, the CDC said.

Those three jurisdictions currently report the following:

• reported four new cases from July 3 to July 11 and is up to 175 cases for the year.
• had one new case from July 1 to July 8 and is now at 564 for the year.
• reported two cases from July 1 to July 10 and is now at 10 for the year (the other two counties have a total of three cases). Clark County in Washington reported 71 cases in an earlier, unrelated outbreak.

[email protected]

The United States continues to slowly add new cases of measles to 2019’s postelimination-record total, but California was officially removed from the outbreak list this week, according to the Centers for Disease Control and Prevention.

There were 14 new measles cases reported during the week ending July 11, bringing the total for the year to 1,123 in 28 states, the CDC reported July 15. That is the highest number of cases reported since measles was declared eliminated in 2000 and the most in a single year since 1992.

The end of outbreak-related activity in California leaves three locations still dealing with ongoing cases: Rockland County, N.Y.; New York City; and King, Pierce, and Snohomish Counties in Washington, the CDC said.

Those three jurisdictions currently report the following:

• reported four new cases from July 3 to July 11 and is up to 175 cases for the year.
• had one new case from July 1 to July 8 and is now at 564 for the year.
• reported two cases from July 1 to July 10 and is now at 10 for the year (the other two counties have a total of three cases). Clark County in Washington reported 71 cases in an earlier, unrelated outbreak.

[email protected]

MADRID – Two major changes that improved RA management in recent years – the introduction of potent biologic and targeted synthetic drugs to control inflammatory disease, and the treat-to-target strategy – have also produced an unanticipated snag in the care patients receive. Their persistent comorbidities and their more atypical rheumatoid manifestations often go overlooked and untreated.

The situation has been dubbed “DAS blindness,” when clinicians caring for patients with RA are so focused on a patient’s disease activity score (DAS), measured by counting their swollen and tender joints (usually 28 joints to tally the DAS28 score), that they lose sight of other important features of a RA patient’s disease such as pain and fatigue, Ruth Williams, MBChB, said in an invited talk at the European Congress of Rheumatology.

“There is so much focus on the DAS28 that people are blinded by it. Clinicians concentrate too much on the primary physical condition” of RA, “and they miss important functional, psychological, and social impacts of the disease,” said Dr. Williams, a general-practice physician who is also a long-time RA patient who works as a patient representative and RA researcher at King’s College London.

In Dr. William’s extended personal experience as an RA patient (she was first diagnosed in 1966 as a child), management of the disease changed dramatically with the relatively recent, widespread adoption of the DAS28 score in routine clinical practice in Europe and the United States, migrating from its initial use in research studies. Once her clinicians began to use the DAS28 “I felt that perhaps I wasn’t being seen anymore. It was just the biology of my disease being noted rather than me as an individual,” Dr. Williams said in an interview. Clinicians “need to discuss with patients what remission means to them, and their objectives” from treatment, because a patient’s treatment goals may go beyond just reducing the number of swollen or tender joints they total in the DAS28 assessment.

Rheumatologists also have begun to recognize this common disconnect between both the assessment and the antirheumatoid treatment that RA patients routinely receive, and the symptoms that cause problems for RA patients that are not directly tied to their inflammatory disease. Patients can present with remission-level responses in their tender and swollen joint counts and in their serum level of C-reactive protein or erythrocyte sedimentation rate but still score high on the patient global assessment (PGA) scale, a residual consequence of RA that places them out of remission range based on the 2011 “Boolean” criteria for RA remission in trials endorsed by the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) (Arthritis Rheum. 2011 Mar;63[3]:373-86).

In a review of 411 RA patients who met three of the four ACR/EULAR criteria that collectively define remission, 61% missed on the PGA measure (Ann Rheum Dis. 2012 Oct;71[10]:1702-5), noted Joan M. Bathon, MD, professor of medicine and director of rheumatology at Columbia University, New York, in a talk during the Congress. Another review of 273 RA patients who missed on one of the four criteria showed 80% missing because of their PGA score (Arthritis Res Ther. 2013;15:R221). The specific clinical features that triggered high PGAs in these patients were things like fibromyalgia, back pain, anxiety, depression, and rheumatoid activity in joints not included in the DAS28 score, Dr. Bathon noted. The PGA can have poor correlation with the other three measures, but that is a strength because it reflects different dimensions of RA that are important to patients. When the PGA is discordant with the other three measures of remission, it may not make sense to try to improve it by simply using more immunosuppressive treatment.

The solution to the dilemma of what remission target to aim for when treating to target is to apply common sense to existing guidelines and recommendations and tailor management to each patient, she concluded. “The worst thing we can do is to take criteria meant for clinical rials and for patients with average scores and apply them to every individual patient,” she said. Remission guidelines are good for large populations, “but we shouldn’t apply them to every single patient without thinking.”

A similar plea for thoughtful use of the treat-to-target model and immunomodulatory treatment came in a separate talk from Laure Gossec, MD, a professor of rheumatology at Pitie-Salpétriere Hospital and Sorbonne University in Paris.

The challenge of DAS28 is that it was a remission criteria developed by the ACR and EULAR to use in clinical trials that was coopted for use in routine practice. Despite that, Dr. Gossec believes that DAS28 largely succeeded in this transition. “The DAS28 performs well, it has good prognostic capacity and is widely used.” In her practice, Dr. Gossec relies on the DAS28 score as her primary tool to track disease status in RA patients. “It’s not perfect, but I’m familiar with it, and I work with it,” she said.

It’s undeniable, she acknowledged, that a high PGA often stands between a patient and remission. PGA “is hard to use to guide anti-inflammatory treatment. Many patients have high PGA scores even though they have no inflammation.” Discrepancies like this create a case for dual-treatment targets, both a low swollen and tender joint count and low PGA, as separate and equal treatment goals, Dr. Gossec said, an approach she and her associates proposed in a recent article (Arthritis Care Res. 2018 Mar;709[3]:369-78).

Dr. Williams had no disclosures. Dr. Bathon has been a consultant to AbbVie and has received research funding from Bristol-Myers Squibb and Pfizer. Dr. Gossec has been a consultant to and has received research funding from several companies.

[email protected]

MADRID – Two major changes that improved RA management in recent years – the introduction of potent biologic and targeted synthetic drugs to control inflammatory disease, and the treat-to-target strategy – have also produced an unanticipated snag in the care patients receive. Their persistent comorbidities and their more atypical rheumatoid manifestations often go overlooked and untreated.

The situation has been dubbed “DAS blindness,” when clinicians caring for patients with RA are so focused on a patient’s disease activity score (DAS), measured by counting their swollen and tender joints (usually 28 joints to tally the DAS28 score), that they lose sight of other important features of a RA patient’s disease such as pain and fatigue, Ruth Williams, MBChB, said in an invited talk at the European Congress of Rheumatology.

“There is so much focus on the DAS28 that people are blinded by it. Clinicians concentrate too much on the primary physical condition” of RA, “and they miss important functional, psychological, and social impacts of the disease,” said Dr. Williams, a general-practice physician who is also a long-time RA patient who works as a patient representative and RA researcher at King’s College London.

In Dr. William’s extended personal experience as an RA patient (she was first diagnosed in 1966 as a child), management of the disease changed dramatically with the relatively recent, widespread adoption of the DAS28 score in routine clinical practice in Europe and the United States, migrating from its initial use in research studies. Once her clinicians began to use the DAS28 “I felt that perhaps I wasn’t being seen anymore. It was just the biology of my disease being noted rather than me as an individual,” Dr. Williams said in an interview. Clinicians “need to discuss with patients what remission means to them, and their objectives” from treatment, because a patient’s treatment goals may go beyond just reducing the number of swollen or tender joints they total in the DAS28 assessment.

Rheumatologists also have begun to recognize this common disconnect between both the assessment and the antirheumatoid treatment that RA patients routinely receive, and the symptoms that cause problems for RA patients that are not directly tied to their inflammatory disease. Patients can present with remission-level responses in their tender and swollen joint counts and in their serum level of C-reactive protein or erythrocyte sedimentation rate but still score high on the patient global assessment (PGA) scale, a residual consequence of RA that places them out of remission range based on the 2011 “Boolean” criteria for RA remission in trials endorsed by the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) (Arthritis Rheum. 2011 Mar;63[3]:373-86).

In a review of 411 RA patients who met three of the four ACR/EULAR criteria that collectively define remission, 61% missed on the PGA measure (Ann Rheum Dis. 2012 Oct;71[10]:1702-5), noted Joan M. Bathon, MD, professor of medicine and director of rheumatology at Columbia University, New York, in a talk during the Congress. Another review of 273 RA patients who missed on one of the four criteria showed 80% missing because of their PGA score (Arthritis Res Ther. 2013;15:R221). The specific clinical features that triggered high PGAs in these patients were things like fibromyalgia, back pain, anxiety, depression, and rheumatoid activity in joints not included in the DAS28 score, Dr. Bathon noted. The PGA can have poor correlation with the other three measures, but that is a strength because it reflects different dimensions of RA that are important to patients. When the PGA is discordant with the other three measures of remission, it may not make sense to try to improve it by simply using more immunosuppressive treatment.

The solution to the dilemma of what remission target to aim for when treating to target is to apply common sense to existing guidelines and recommendations and tailor management to each patient, she concluded. “The worst thing we can do is to take criteria meant for clinical rials and for patients with average scores and apply them to every individual patient,” she said. Remission guidelines are good for large populations, “but we shouldn’t apply them to every single patient without thinking.”

A similar plea for thoughtful use of the treat-to-target model and immunomodulatory treatment came in a separate talk from Laure Gossec, MD, a professor of rheumatology at Pitie-Salpétriere Hospital and Sorbonne University in Paris.

The challenge of DAS28 is that it was a remission criteria developed by the ACR and EULAR to use in clinical trials that was coopted for use in routine practice. Despite that, Dr. Gossec believes that DAS28 largely succeeded in this transition. “The DAS28 performs well, it has good prognostic capacity and is widely used.” In her practice, Dr. Gossec relies on the DAS28 score as her primary tool to track disease status in RA patients. “It’s not perfect, but I’m familiar with it, and I work with it,” she said.

It’s undeniable, she acknowledged, that a high PGA often stands between a patient and remission. PGA “is hard to use to guide anti-inflammatory treatment. Many patients have high PGA scores even though they have no inflammation.” Discrepancies like this create a case for dual-treatment targets, both a low swollen and tender joint count and low PGA, as separate and equal treatment goals, Dr. Gossec said, an approach she and her associates proposed in a recent article (Arthritis Care Res. 2018 Mar;709[3]:369-78).

Dr. Williams had no disclosures. Dr. Bathon has been a consultant to AbbVie and has received research funding from Bristol-Myers Squibb and Pfizer. Dr. Gossec has been a consultant to and has received research funding from several companies.

[email protected]

MADRID – Two major changes that improved RA management in recent years – the introduction of potent biologic and targeted synthetic drugs to control inflammatory disease, and the treat-to-target strategy – have also produced an unanticipated snag in the care patients receive. Their persistent comorbidities and their more atypical rheumatoid manifestations often go overlooked and untreated.

The situation has been dubbed “DAS blindness,” when clinicians caring for patients with RA are so focused on a patient’s disease activity score (DAS), measured by counting their swollen and tender joints (usually 28 joints to tally the DAS28 score), that they lose sight of other important features of a RA patient’s disease such as pain and fatigue, Ruth Williams, MBChB, said in an invited talk at the European Congress of Rheumatology.

“There is so much focus on the DAS28 that people are blinded by it. Clinicians concentrate too much on the primary physical condition” of RA, “and they miss important functional, psychological, and social impacts of the disease,” said Dr. Williams, a general-practice physician who is also a long-time RA patient who works as a patient representative and RA researcher at King’s College London.

In Dr. William’s extended personal experience as an RA patient (she was first diagnosed in 1966 as a child), management of the disease changed dramatically with the relatively recent, widespread adoption of the DAS28 score in routine clinical practice in Europe and the United States, migrating from its initial use in research studies. Once her clinicians began to use the DAS28 “I felt that perhaps I wasn’t being seen anymore. It was just the biology of my disease being noted rather than me as an individual,” Dr. Williams said in an interview. Clinicians “need to discuss with patients what remission means to them, and their objectives” from treatment, because a patient’s treatment goals may go beyond just reducing the number of swollen or tender joints they total in the DAS28 assessment.

Rheumatologists also have begun to recognize this common disconnect between both the assessment and the antirheumatoid treatment that RA patients routinely receive, and the symptoms that cause problems for RA patients that are not directly tied to their inflammatory disease. Patients can present with remission-level responses in their tender and swollen joint counts and in their serum level of C-reactive protein or erythrocyte sedimentation rate but still score high on the patient global assessment (PGA) scale, a residual consequence of RA that places them out of remission range based on the 2011 “Boolean” criteria for RA remission in trials endorsed by the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) (Arthritis Rheum. 2011 Mar;63[3]:373-86).

In a review of 411 RA patients who met three of the four ACR/EULAR criteria that collectively define remission, 61% missed on the PGA measure (Ann Rheum Dis. 2012 Oct;71[10]:1702-5), noted Joan M. Bathon, MD, professor of medicine and director of rheumatology at Columbia University, New York, in a talk during the Congress. Another review of 273 RA patients who missed on one of the four criteria showed 80% missing because of their PGA score (Arthritis Res Ther. 2013;15:R221). The specific clinical features that triggered high PGAs in these patients were things like fibromyalgia, back pain, anxiety, depression, and rheumatoid activity in joints not included in the DAS28 score, Dr. Bathon noted. The PGA can have poor correlation with the other three measures, but that is a strength because it reflects different dimensions of RA that are important to patients. When the PGA is discordant with the other three measures of remission, it may not make sense to try to improve it by simply using more immunosuppressive treatment.

The solution to the dilemma of what remission target to aim for when treating to target is to apply common sense to existing guidelines and recommendations and tailor management to each patient, she concluded. “The worst thing we can do is to take criteria meant for clinical rials and for patients with average scores and apply them to every individual patient,” she said. Remission guidelines are good for large populations, “but we shouldn’t apply them to every single patient without thinking.”

A similar plea for thoughtful use of the treat-to-target model and immunomodulatory treatment came in a separate talk from Laure Gossec, MD, a professor of rheumatology at Pitie-Salpétriere Hospital and Sorbonne University in Paris.

The challenge of DAS28 is that it was a remission criteria developed by the ACR and EULAR to use in clinical trials that was coopted for use in routine practice. Despite that, Dr. Gossec believes that DAS28 largely succeeded in this transition. “The DAS28 performs well, it has good prognostic capacity and is widely used.” In her practice, Dr. Gossec relies on the DAS28 score as her primary tool to track disease status in RA patients. “It’s not perfect, but I’m familiar with it, and I work with it,” she said.

It’s undeniable, she acknowledged, that a high PGA often stands between a patient and remission. PGA “is hard to use to guide anti-inflammatory treatment. Many patients have high PGA scores even though they have no inflammation.” Discrepancies like this create a case for dual-treatment targets, both a low swollen and tender joint count and low PGA, as separate and equal treatment goals, Dr. Gossec said, an approach she and her associates proposed in a recent article (Arthritis Care Res. 2018 Mar;709[3]:369-78).

Dr. Williams had no disclosures. Dr. Bathon has been a consultant to AbbVie and has received research funding from Bristol-Myers Squibb and Pfizer. Dr. Gossec has been a consultant to and has received research funding from several companies.

[email protected]

ANSWER

The radiograph demonstrates no evidence of an acute fracture or soft-tissue gas to suggest an abscess. Of note, though, within the tibiotalar joint, the patient has bony destruction and settling of the articular surfaces of both the distal tibia and fibula into the talus and calcaneus.

This finding is typically associated with neuropathic arthropathy (also known as a Charcot joint). This pathologic process is typically seen in a weight-bearing joint that develops progressive degeneration from chronic loss of sensation.

ANSWER

The radiograph demonstrates no evidence of an acute fracture or soft-tissue gas to suggest an abscess. Of note, though, within the tibiotalar joint, the patient has bony destruction and settling of the articular surfaces of both the distal tibia and fibula into the talus and calcaneus.

This finding is typically associated with neuropathic arthropathy (also known as a Charcot joint). This pathologic process is typically seen in a weight-bearing joint that develops progressive degeneration from chronic loss of sensation.

ANSWER

The radiograph demonstrates no evidence of an acute fracture or soft-tissue gas to suggest an abscess. Of note, though, within the tibiotalar joint, the patient has bony destruction and settling of the articular surfaces of both the distal tibia and fibula into the talus and calcaneus.

This finding is typically associated with neuropathic arthropathy (also known as a Charcot joint). This pathologic process is typically seen in a weight-bearing joint that develops progressive degeneration from chronic loss of sensation.

The gut microbiota influences our biology through our mucosal immune system as well as by leading to the production of bioactive small molecules. I’ll describe how gut microbiota influences colon cancer, liver disease, the production of bioactive compounds, as well as the current status and future prospects of microbiota therapeutics.

The gut microbiota may be a factor in colon cancer. Studies have shown that bacterial biofilms are associated with right-sided colon cancers in humans. More recently, a study has shown that mucosal biofilm formation is carcinogenic in an animal model, suggesting that such biofilms may play a role in the disease pathogenesis. From the standpoint of the liver, the microbiome may be a biomarker for diseases such as cirrhosis and fibrosis in patients with nonalcoholic steatohepatitis. Therapeutically, a recent study suggests that the function of gut microbiota can be altered by introducing an engineered Escherichia coli bacterial strain to treat hyperammonemia by modifying its metabolism to overproduce arginine, thereby sequestering ammonia produced by gut bacteria into the amino acids (Sci Transl Med. 2019 Jan 16;11[475]. doi: 10.1126/scitranslmed.aau7975). Drug metabolism also can be influenced by the gut microbiota and vice versa. For example, drugs such as metformin have effects on the composition of the gut microbiota in humans. In turn, the gut microbiota and its metabolites can have an influence on hepatic drug metabolism, thereby altering xenobiotic pharmacokinetics and pharmacodynamics.

The production of bioactive small molecules by bacterial metabolism is a topic of intense interest in the microbiome field. Such small molecules have been shown to act as antibiotics, neurotransmitters, immune modulators, and ligands for host receptors. Some of these small metabolites are generated through the dietary aromatic amino acids in which the bacterial enzymatic pathways are being elucidated. Such small molecules have a myriad of functions. For example, indole propionic acid, a bacterial metabolite of tryptophan, can activate the pregnane X receptor to fortify intestinal epithelial barrier function, a pathway that may have relevance to inflammatory bowel disease.

Probiotics that are found in dietary supplements represent our currently available strategy for the prevention and/or treatment of disease through the delivery of specific live microbes. However, there are limitations to their effectiveness since none have been approved for the prevention or treatment of any disease process. Via an intensive human subject study, (Cell. 2018 Sep 6;174[6]:1388-405) investigators have shown that the mucosally associated microbiota was a better biomarker for probiotic engraftment than stool was, where the response was very personalized. It’s possible that the personalized nature of probiotic engraftment may indicate that “one size may not fit all.” There will be a technical review and guideline document published by the American Gastroenterological Association early in 2020.

Currently, the only effective therapeutic modality for the treatment of a human disease by deeply altering the composition of the gut microbiota is the use of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridium difficile infection (CDI). However, there is now early evidence that FMT might have efficacy in the treatment of a disease other than recurrent CDI, namely ulcerative colitis. Although the short-term risks for FMT are low and quantifiable and long-term risks are largely hypothetical, there is a need for caution and regulation in the practice of FMT. Indeed, long-term engraftment of bacterial strains from the donor into the recipient has been demonstrated. Ultimately, as the science in the microbiota field moves forward together with product development, more sophisticated microbiota-based therapeutics will be generated. During this interim period, the AGA and partner national societies have developed an FMT National Registry to gather information on FMT practice, assess effectiveness as well as short- and long-term safety, and promote scientific investigation.

In conclusion, the field of gut microbiome research is very dynamic and exciting with tremendous opportunities at the intersection between fabulous science and technology, clinical practice, and federal regulation involving the practice of FMT, concurrent in a significant interest in intellectual property and business.
 

Dr. Wu is the Ferdinand G. Weisbrod Professor in Gastroenterology at the University of Pennsylvania, Philadelphia. He has received research funding from Seres Therapeutics, Intercept Pharmaceuticals, and Takeda; is on the scientific advisory board for Danone and Biocodex; and does consulting for Hitachi High-Technologies. Dr. Wu made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

The gut microbiota influences our biology through our mucosal immune system as well as by leading to the production of bioactive small molecules. I’ll describe how gut microbiota influences colon cancer, liver disease, the production of bioactive compounds, as well as the current status and future prospects of microbiota therapeutics.

The gut microbiota may be a factor in colon cancer. Studies have shown that bacterial biofilms are associated with right-sided colon cancers in humans. More recently, a study has shown that mucosal biofilm formation is carcinogenic in an animal model, suggesting that such biofilms may play a role in the disease pathogenesis. From the standpoint of the liver, the microbiome may be a biomarker for diseases such as cirrhosis and fibrosis in patients with nonalcoholic steatohepatitis. Therapeutically, a recent study suggests that the function of gut microbiota can be altered by introducing an engineered Escherichia coli bacterial strain to treat hyperammonemia by modifying its metabolism to overproduce arginine, thereby sequestering ammonia produced by gut bacteria into the amino acids (Sci Transl Med. 2019 Jan 16;11[475]. doi: 10.1126/scitranslmed.aau7975). Drug metabolism also can be influenced by the gut microbiota and vice versa. For example, drugs such as metformin have effects on the composition of the gut microbiota in humans. In turn, the gut microbiota and its metabolites can have an influence on hepatic drug metabolism, thereby altering xenobiotic pharmacokinetics and pharmacodynamics.

The production of bioactive small molecules by bacterial metabolism is a topic of intense interest in the microbiome field. Such small molecules have been shown to act as antibiotics, neurotransmitters, immune modulators, and ligands for host receptors. Some of these small metabolites are generated through the dietary aromatic amino acids in which the bacterial enzymatic pathways are being elucidated. Such small molecules have a myriad of functions. For example, indole propionic acid, a bacterial metabolite of tryptophan, can activate the pregnane X receptor to fortify intestinal epithelial barrier function, a pathway that may have relevance to inflammatory bowel disease.

Probiotics that are found in dietary supplements represent our currently available strategy for the prevention and/or treatment of disease through the delivery of specific live microbes. However, there are limitations to their effectiveness since none have been approved for the prevention or treatment of any disease process. Via an intensive human subject study, (Cell. 2018 Sep 6;174[6]:1388-405) investigators have shown that the mucosally associated microbiota was a better biomarker for probiotic engraftment than stool was, where the response was very personalized. It’s possible that the personalized nature of probiotic engraftment may indicate that “one size may not fit all.” There will be a technical review and guideline document published by the American Gastroenterological Association early in 2020.

Currently, the only effective therapeutic modality for the treatment of a human disease by deeply altering the composition of the gut microbiota is the use of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridium difficile infection (CDI). However, there is now early evidence that FMT might have efficacy in the treatment of a disease other than recurrent CDI, namely ulcerative colitis. Although the short-term risks for FMT are low and quantifiable and long-term risks are largely hypothetical, there is a need for caution and regulation in the practice of FMT. Indeed, long-term engraftment of bacterial strains from the donor into the recipient has been demonstrated. Ultimately, as the science in the microbiota field moves forward together with product development, more sophisticated microbiota-based therapeutics will be generated. During this interim period, the AGA and partner national societies have developed an FMT National Registry to gather information on FMT practice, assess effectiveness as well as short- and long-term safety, and promote scientific investigation.

In conclusion, the field of gut microbiome research is very dynamic and exciting with tremendous opportunities at the intersection between fabulous science and technology, clinical practice, and federal regulation involving the practice of FMT, concurrent in a significant interest in intellectual property and business.
 

Dr. Wu is the Ferdinand G. Weisbrod Professor in Gastroenterology at the University of Pennsylvania, Philadelphia. He has received research funding from Seres Therapeutics, Intercept Pharmaceuticals, and Takeda; is on the scientific advisory board for Danone and Biocodex; and does consulting for Hitachi High-Technologies. Dr. Wu made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

The gut microbiota influences our biology through our mucosal immune system as well as by leading to the production of bioactive small molecules. I’ll describe how gut microbiota influences colon cancer, liver disease, the production of bioactive compounds, as well as the current status and future prospects of microbiota therapeutics.

The gut microbiota may be a factor in colon cancer. Studies have shown that bacterial biofilms are associated with right-sided colon cancers in humans. More recently, a study has shown that mucosal biofilm formation is carcinogenic in an animal model, suggesting that such biofilms may play a role in the disease pathogenesis. From the standpoint of the liver, the microbiome may be a biomarker for diseases such as cirrhosis and fibrosis in patients with nonalcoholic steatohepatitis. Therapeutically, a recent study suggests that the function of gut microbiota can be altered by introducing an engineered Escherichia coli bacterial strain to treat hyperammonemia by modifying its metabolism to overproduce arginine, thereby sequestering ammonia produced by gut bacteria into the amino acids (Sci Transl Med. 2019 Jan 16;11[475]. doi: 10.1126/scitranslmed.aau7975). Drug metabolism also can be influenced by the gut microbiota and vice versa. For example, drugs such as metformin have effects on the composition of the gut microbiota in humans. In turn, the gut microbiota and its metabolites can have an influence on hepatic drug metabolism, thereby altering xenobiotic pharmacokinetics and pharmacodynamics.

The production of bioactive small molecules by bacterial metabolism is a topic of intense interest in the microbiome field. Such small molecules have been shown to act as antibiotics, neurotransmitters, immune modulators, and ligands for host receptors. Some of these small metabolites are generated through the dietary aromatic amino acids in which the bacterial enzymatic pathways are being elucidated. Such small molecules have a myriad of functions. For example, indole propionic acid, a bacterial metabolite of tryptophan, can activate the pregnane X receptor to fortify intestinal epithelial barrier function, a pathway that may have relevance to inflammatory bowel disease.

Probiotics that are found in dietary supplements represent our currently available strategy for the prevention and/or treatment of disease through the delivery of specific live microbes. However, there are limitations to their effectiveness since none have been approved for the prevention or treatment of any disease process. Via an intensive human subject study, (Cell. 2018 Sep 6;174[6]:1388-405) investigators have shown that the mucosally associated microbiota was a better biomarker for probiotic engraftment than stool was, where the response was very personalized. It’s possible that the personalized nature of probiotic engraftment may indicate that “one size may not fit all.” There will be a technical review and guideline document published by the American Gastroenterological Association early in 2020.

Currently, the only effective therapeutic modality for the treatment of a human disease by deeply altering the composition of the gut microbiota is the use of fecal microbiota transplantation (FMT) for the treatment of recurrent Clostridium difficile infection (CDI). However, there is now early evidence that FMT might have efficacy in the treatment of a disease other than recurrent CDI, namely ulcerative colitis. Although the short-term risks for FMT are low and quantifiable and long-term risks are largely hypothetical, there is a need for caution and regulation in the practice of FMT. Indeed, long-term engraftment of bacterial strains from the donor into the recipient has been demonstrated. Ultimately, as the science in the microbiota field moves forward together with product development, more sophisticated microbiota-based therapeutics will be generated. During this interim period, the AGA and partner national societies have developed an FMT National Registry to gather information on FMT practice, assess effectiveness as well as short- and long-term safety, and promote scientific investigation.

In conclusion, the field of gut microbiome research is very dynamic and exciting with tremendous opportunities at the intersection between fabulous science and technology, clinical practice, and federal regulation involving the practice of FMT, concurrent in a significant interest in intellectual property and business.
 

Dr. Wu is the Ferdinand G. Weisbrod Professor in Gastroenterology at the University of Pennsylvania, Philadelphia. He has received research funding from Seres Therapeutics, Intercept Pharmaceuticals, and Takeda; is on the scientific advisory board for Danone and Biocodex; and does consulting for Hitachi High-Technologies. Dr. Wu made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

Many of the personnel questions I receive concern the dreaded “marginal employee” – a person who has never done anything truly heinous to merit firing, but neither anything special to merit continued employment. I advise getting rid of such people and then changing the hiring criteria that bring you marginal employees in the first place.

katleho Seisa/Getty Images

Most bad hires come about because employers do not have a clear vision of the kind of employee they want. Many office manuals do not contain detailed job descriptions. If you don’t know exactly what you are looking for, your entire selection process will be inadequate from initial screening of applicants through assessments of their skills and personalities. Many physicians compound the problem with poor interview techniques and inadequate verification.

So now is the time, before a job vacancy occurs, to reevaluate your entire hiring process.. Take a hard look at your job descriptions, and update them if necessary. A good job description lists the major responsibilities of the position, with the relative importance of each duty and the critical knowledge, skills, and education levels necessary for each function. In other words, it describes, accurately and in detail, exactly what you expect from the employee you will hire to perform that job.

Once you have a clear job description in mind (and in print), take all the time you need to find the best possible match for it. This is not a place to cut corners. Screen your candidates carefully and avoid lowering your expectations. This is the point at which it might be tempting to settle for a marginal candidate, just to get the process over with.

It also is tempting to hire the candidate that you have the “best feeling” about, even though he or she is a poor match for the job, and then try to mold the job to that person. Every doctor knows that hunches are no substitute for hard data.


Be alert for red flags in résumés: significant time gaps between jobs; positions at companies that are no longer in business, or are otherwise impossible to verify; job titles that don’t make sense, given the applicant’s qualifications.

Background checks are a dicey subject, but publicly available information can be found, cheaply or free, on multiple websites created for that purpose. Be sure to tell applicants that you will be verifying facts in their résumés; it’s usually wise to get their written consent to do so.

Many employers skip the essential step of verification; many applicants know that. (I once actually overheard a new hire say, “I won’t be here long if they check my references.” And by golly, she was right!) If a reference is reluctant to tell you anything substantive, ask, “Would you hire this person again?” You can interpret a lot from the answer – or lack of one.

Interviews often get short shrift as well. Many doctors tend to do all the talking. The purpose of an interview is to allow you to size up the prospective employee, not to deliver a lecture on the sterling attributes of your office. Important interview topics include educational background, skills, experience, and unrelated job history.

By law, you cannot ask an applicant’s age, date of birth, sex, creed, color, religion, or national origin. Other forbidden subjects include disabilities, marital status, military record, number of children (or who cares for them), addiction history, citizenship, criminal record, psychiatric history, absenteeism, or workers’ compensation.

There are acceptable alternatives to some of those questions, however: You can ask if applicants have ever gone by another name (for your background check), for example. You can ask if they are legally authorized to work in this country, and whether they will be physically able to perform the duties specified in the job description. While past addictions are off limits, you do have a right to know about current addictions to illegal substances.

Once you have hired people whose skills and personalities best fit your needs, train them well, and then give them the opportunity to succeed. “The best executive,” wrote Theodore Roosevelt, “is the one who has sense enough to pick good [people] to do what he [or she] wants done, and self-restraint enough to keep from meddling with them while they do it.”
 

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

Many of the personnel questions I receive concern the dreaded “marginal employee” – a person who has never done anything truly heinous to merit firing, but neither anything special to merit continued employment. I advise getting rid of such people and then changing the hiring criteria that bring you marginal employees in the first place.

katleho Seisa/Getty Images

Most bad hires come about because employers do not have a clear vision of the kind of employee they want. Many office manuals do not contain detailed job descriptions. If you don’t know exactly what you are looking for, your entire selection process will be inadequate from initial screening of applicants through assessments of their skills and personalities. Many physicians compound the problem with poor interview techniques and inadequate verification.

So now is the time, before a job vacancy occurs, to reevaluate your entire hiring process.. Take a hard look at your job descriptions, and update them if necessary. A good job description lists the major responsibilities of the position, with the relative importance of each duty and the critical knowledge, skills, and education levels necessary for each function. In other words, it describes, accurately and in detail, exactly what you expect from the employee you will hire to perform that job.

Once you have a clear job description in mind (and in print), take all the time you need to find the best possible match for it. This is not a place to cut corners. Screen your candidates carefully and avoid lowering your expectations. This is the point at which it might be tempting to settle for a marginal candidate, just to get the process over with.

It also is tempting to hire the candidate that you have the “best feeling” about, even though he or she is a poor match for the job, and then try to mold the job to that person. Every doctor knows that hunches are no substitute for hard data.


Be alert for red flags in résumés: significant time gaps between jobs; positions at companies that are no longer in business, or are otherwise impossible to verify; job titles that don’t make sense, given the applicant’s qualifications.

Background checks are a dicey subject, but publicly available information can be found, cheaply or free, on multiple websites created for that purpose. Be sure to tell applicants that you will be verifying facts in their résumés; it’s usually wise to get their written consent to do so.

Many employers skip the essential step of verification; many applicants know that. (I once actually overheard a new hire say, “I won’t be here long if they check my references.” And by golly, she was right!) If a reference is reluctant to tell you anything substantive, ask, “Would you hire this person again?” You can interpret a lot from the answer – or lack of one.

Interviews often get short shrift as well. Many doctors tend to do all the talking. The purpose of an interview is to allow you to size up the prospective employee, not to deliver a lecture on the sterling attributes of your office. Important interview topics include educational background, skills, experience, and unrelated job history.

By law, you cannot ask an applicant’s age, date of birth, sex, creed, color, religion, or national origin. Other forbidden subjects include disabilities, marital status, military record, number of children (or who cares for them), addiction history, citizenship, criminal record, psychiatric history, absenteeism, or workers’ compensation.

There are acceptable alternatives to some of those questions, however: You can ask if applicants have ever gone by another name (for your background check), for example. You can ask if they are legally authorized to work in this country, and whether they will be physically able to perform the duties specified in the job description. While past addictions are off limits, you do have a right to know about current addictions to illegal substances.

Once you have hired people whose skills and personalities best fit your needs, train them well, and then give them the opportunity to succeed. “The best executive,” wrote Theodore Roosevelt, “is the one who has sense enough to pick good [people] to do what he [or she] wants done, and self-restraint enough to keep from meddling with them while they do it.”
 

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

Many of the personnel questions I receive concern the dreaded “marginal employee” – a person who has never done anything truly heinous to merit firing, but neither anything special to merit continued employment. I advise getting rid of such people and then changing the hiring criteria that bring you marginal employees in the first place.

katleho Seisa/Getty Images

Most bad hires come about because employers do not have a clear vision of the kind of employee they want. Many office manuals do not contain detailed job descriptions. If you don’t know exactly what you are looking for, your entire selection process will be inadequate from initial screening of applicants through assessments of their skills and personalities. Many physicians compound the problem with poor interview techniques and inadequate verification.

So now is the time, before a job vacancy occurs, to reevaluate your entire hiring process.. Take a hard look at your job descriptions, and update them if necessary. A good job description lists the major responsibilities of the position, with the relative importance of each duty and the critical knowledge, skills, and education levels necessary for each function. In other words, it describes, accurately and in detail, exactly what you expect from the employee you will hire to perform that job.

Once you have a clear job description in mind (and in print), take all the time you need to find the best possible match for it. This is not a place to cut corners. Screen your candidates carefully and avoid lowering your expectations. This is the point at which it might be tempting to settle for a marginal candidate, just to get the process over with.

It also is tempting to hire the candidate that you have the “best feeling” about, even though he or she is a poor match for the job, and then try to mold the job to that person. Every doctor knows that hunches are no substitute for hard data.


Be alert for red flags in résumés: significant time gaps between jobs; positions at companies that are no longer in business, or are otherwise impossible to verify; job titles that don’t make sense, given the applicant’s qualifications.

Background checks are a dicey subject, but publicly available information can be found, cheaply or free, on multiple websites created for that purpose. Be sure to tell applicants that you will be verifying facts in their résumés; it’s usually wise to get their written consent to do so.

Many employers skip the essential step of verification; many applicants know that. (I once actually overheard a new hire say, “I won’t be here long if they check my references.” And by golly, she was right!) If a reference is reluctant to tell you anything substantive, ask, “Would you hire this person again?” You can interpret a lot from the answer – or lack of one.

Interviews often get short shrift as well. Many doctors tend to do all the talking. The purpose of an interview is to allow you to size up the prospective employee, not to deliver a lecture on the sterling attributes of your office. Important interview topics include educational background, skills, experience, and unrelated job history.

By law, you cannot ask an applicant’s age, date of birth, sex, creed, color, religion, or national origin. Other forbidden subjects include disabilities, marital status, military record, number of children (or who cares for them), addiction history, citizenship, criminal record, psychiatric history, absenteeism, or workers’ compensation.

There are acceptable alternatives to some of those questions, however: You can ask if applicants have ever gone by another name (for your background check), for example. You can ask if they are legally authorized to work in this country, and whether they will be physically able to perform the duties specified in the job description. While past addictions are off limits, you do have a right to know about current addictions to illegal substances.

Once you have hired people whose skills and personalities best fit your needs, train them well, and then give them the opportunity to succeed. “The best executive,” wrote Theodore Roosevelt, “is the one who has sense enough to pick good [people] to do what he [or she] wants done, and self-restraint enough to keep from meddling with them while they do it.”
 

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

A description of ulcerative colitis (UC) was first published by Wilkes in 1875. Infliximab was approved by the Food and Drug Administration for Crohn’s disease (CD) in 1998, 123 years later. However, in the following 20 years, there were eight new biologic or small-molecule agents approved for inflammatory bowel disease (IBD), with dozens more in the pipeline. These new mechanisms of action include janus kinase (JAK) inhibition, sphingosine 1 phosphate receptor 1 modulation, anti-integrins, and inhibition of the p19 subunit of interleukin-23.

Unfortunately, the rapid increase in drugs and mechanisms of action have not come with a strong understanding of which agent is most appropriate for which patient. Recent studies have tried to address parts of this question. First, we must define what the endpoints of therapy are – endoscopy, histology, or patient-reported outcomes? Then we need to understand how to achieve these endpoints. Combined immunosuppression with infliximab and azathioprine was superior to each alone in the SONIC trial (N Engl J Med. 2010;362:1383-95). The CALM study (Lancet. 2018;390:2779-89) looked at clinical management (escalation in therapy for moderate to severe CD by Crohn’s Disease Activity Index [CDAI]) and prednisone use versus a treat-to-target (T2T) approach which responded to C-reactive protein and fecal calprotectin. The T2T approach was statistically more likely to achieve endoscopic response at week 48 (45.9% vs. 30.3%). Early immunosuppression is also more likely to reduce hospitalization and surgery rates as shown in the REACT Trial (Lancet 2015;386:1825-34). This year at Digestive Disease Week, we can also add the VARSITY trial (Abstract 416A) which was a head-to-head comparison of vedolizumab to adalimumab for UC. After induction and maintenance therapy, vedolizumab was statistically more likely to induce clinical remission at week 52 than adalimumab, suggesting vedolizumab should be preferred as the first-line biologic in moderate to severe outpatient UC, particularly given its excellent safety profile.

Ustekinumab is Food and Drug Administration approved for CD. At this year’s DDW we saw that it is effective for induction and maintenance of remission in UC (Abstract 833) as well, and also has an excellent safety profile. JAK inhibitors have shown significant efficacy for UC, and more selective agents with primarily JAK1 inhibition are in studies for CD and UC. Adverse events of interest have included herpes zoster and thromboembolic events. Research has also been focusing on out-of-the-box therapies including fecal microbiota transplant for UC, dietary interventions for induction and maintenance of remission in IBD, and allogenic mesenchymal stem cells for perianal fistulizing CD.

With all of this new therapy, are we actually modifying disease history and avoiding surgery? The answer to that seems to be “yes.” Edward L. Barnes, MD, and colleagues (Abstract 708) used an insurance dataset to show that the rate of colectomy for UC has been reduced significantly between 2007 and 2016. While this may be, in part, attributable to biologic therapy, certainly change in practice guidelines, awareness of complications such as C. difficile, and enhanced disease monitoring have also played a role. Surgery itself should not be viewed as a failure. A limited ileocecal resection is more cost effective with equal or better quality of life at 1 year, compared with infliximab therapy, per the randomized LiRIC trial (Lancet Gastroenterol Hepatol 2017;2:785-92).

Therapy is evolving at a rapid pace, while the disease itself is increasing in incidence and prevalence around the world. To truly manage this patient population, we need to have a population-based intervention (diet, predictive biomarkers, etc.) to help reduce the number of people developing IBD, and a better understanding of when and how to use the mechanisms of action we already have to achieve and maintain remission in patients with IBD.
 

Dr. Mahadevan is professor of medicine, University of California at San Francisco Center for Colitis and Crohn’s Disease. She has disclosed receiving grant or research support from Tigenix, Pfizer, Genentech, and Celgene and being a consultant for Gilead, AbbVie, Bristol-Myers Squibb, Janssen, Takeda, and Lilly. Dr. Mahadevan made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

A description of ulcerative colitis (UC) was first published by Wilkes in 1875. Infliximab was approved by the Food and Drug Administration for Crohn’s disease (CD) in 1998, 123 years later. However, in the following 20 years, there were eight new biologic or small-molecule agents approved for inflammatory bowel disease (IBD), with dozens more in the pipeline. These new mechanisms of action include janus kinase (JAK) inhibition, sphingosine 1 phosphate receptor 1 modulation, anti-integrins, and inhibition of the p19 subunit of interleukin-23.

Unfortunately, the rapid increase in drugs and mechanisms of action have not come with a strong understanding of which agent is most appropriate for which patient. Recent studies have tried to address parts of this question. First, we must define what the endpoints of therapy are – endoscopy, histology, or patient-reported outcomes? Then we need to understand how to achieve these endpoints. Combined immunosuppression with infliximab and azathioprine was superior to each alone in the SONIC trial (N Engl J Med. 2010;362:1383-95). The CALM study (Lancet. 2018;390:2779-89) looked at clinical management (escalation in therapy for moderate to severe CD by Crohn’s Disease Activity Index [CDAI]) and prednisone use versus a treat-to-target (T2T) approach which responded to C-reactive protein and fecal calprotectin. The T2T approach was statistically more likely to achieve endoscopic response at week 48 (45.9% vs. 30.3%). Early immunosuppression is also more likely to reduce hospitalization and surgery rates as shown in the REACT Trial (Lancet 2015;386:1825-34). This year at Digestive Disease Week, we can also add the VARSITY trial (Abstract 416A) which was a head-to-head comparison of vedolizumab to adalimumab for UC. After induction and maintenance therapy, vedolizumab was statistically more likely to induce clinical remission at week 52 than adalimumab, suggesting vedolizumab should be preferred as the first-line biologic in moderate to severe outpatient UC, particularly given its excellent safety profile.

Ustekinumab is Food and Drug Administration approved for CD. At this year’s DDW we saw that it is effective for induction and maintenance of remission in UC (Abstract 833) as well, and also has an excellent safety profile. JAK inhibitors have shown significant efficacy for UC, and more selective agents with primarily JAK1 inhibition are in studies for CD and UC. Adverse events of interest have included herpes zoster and thromboembolic events. Research has also been focusing on out-of-the-box therapies including fecal microbiota transplant for UC, dietary interventions for induction and maintenance of remission in IBD, and allogenic mesenchymal stem cells for perianal fistulizing CD.

With all of this new therapy, are we actually modifying disease history and avoiding surgery? The answer to that seems to be “yes.” Edward L. Barnes, MD, and colleagues (Abstract 708) used an insurance dataset to show that the rate of colectomy for UC has been reduced significantly between 2007 and 2016. While this may be, in part, attributable to biologic therapy, certainly change in practice guidelines, awareness of complications such as C. difficile, and enhanced disease monitoring have also played a role. Surgery itself should not be viewed as a failure. A limited ileocecal resection is more cost effective with equal or better quality of life at 1 year, compared with infliximab therapy, per the randomized LiRIC trial (Lancet Gastroenterol Hepatol 2017;2:785-92).

Therapy is evolving at a rapid pace, while the disease itself is increasing in incidence and prevalence around the world. To truly manage this patient population, we need to have a population-based intervention (diet, predictive biomarkers, etc.) to help reduce the number of people developing IBD, and a better understanding of when and how to use the mechanisms of action we already have to achieve and maintain remission in patients with IBD.
 

Dr. Mahadevan is professor of medicine, University of California at San Francisco Center for Colitis and Crohn’s Disease. She has disclosed receiving grant or research support from Tigenix, Pfizer, Genentech, and Celgene and being a consultant for Gilead, AbbVie, Bristol-Myers Squibb, Janssen, Takeda, and Lilly. Dr. Mahadevan made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

A description of ulcerative colitis (UC) was first published by Wilkes in 1875. Infliximab was approved by the Food and Drug Administration for Crohn’s disease (CD) in 1998, 123 years later. However, in the following 20 years, there were eight new biologic or small-molecule agents approved for inflammatory bowel disease (IBD), with dozens more in the pipeline. These new mechanisms of action include janus kinase (JAK) inhibition, sphingosine 1 phosphate receptor 1 modulation, anti-integrins, and inhibition of the p19 subunit of interleukin-23.

Unfortunately, the rapid increase in drugs and mechanisms of action have not come with a strong understanding of which agent is most appropriate for which patient. Recent studies have tried to address parts of this question. First, we must define what the endpoints of therapy are – endoscopy, histology, or patient-reported outcomes? Then we need to understand how to achieve these endpoints. Combined immunosuppression with infliximab and azathioprine was superior to each alone in the SONIC trial (N Engl J Med. 2010;362:1383-95). The CALM study (Lancet. 2018;390:2779-89) looked at clinical management (escalation in therapy for moderate to severe CD by Crohn’s Disease Activity Index [CDAI]) and prednisone use versus a treat-to-target (T2T) approach which responded to C-reactive protein and fecal calprotectin. The T2T approach was statistically more likely to achieve endoscopic response at week 48 (45.9% vs. 30.3%). Early immunosuppression is also more likely to reduce hospitalization and surgery rates as shown in the REACT Trial (Lancet 2015;386:1825-34). This year at Digestive Disease Week, we can also add the VARSITY trial (Abstract 416A) which was a head-to-head comparison of vedolizumab to adalimumab for UC. After induction and maintenance therapy, vedolizumab was statistically more likely to induce clinical remission at week 52 than adalimumab, suggesting vedolizumab should be preferred as the first-line biologic in moderate to severe outpatient UC, particularly given its excellent safety profile.

Ustekinumab is Food and Drug Administration approved for CD. At this year’s DDW we saw that it is effective for induction and maintenance of remission in UC (Abstract 833) as well, and also has an excellent safety profile. JAK inhibitors have shown significant efficacy for UC, and more selective agents with primarily JAK1 inhibition are in studies for CD and UC. Adverse events of interest have included herpes zoster and thromboembolic events. Research has also been focusing on out-of-the-box therapies including fecal microbiota transplant for UC, dietary interventions for induction and maintenance of remission in IBD, and allogenic mesenchymal stem cells for perianal fistulizing CD.

With all of this new therapy, are we actually modifying disease history and avoiding surgery? The answer to that seems to be “yes.” Edward L. Barnes, MD, and colleagues (Abstract 708) used an insurance dataset to show that the rate of colectomy for UC has been reduced significantly between 2007 and 2016. While this may be, in part, attributable to biologic therapy, certainly change in practice guidelines, awareness of complications such as C. difficile, and enhanced disease monitoring have also played a role. Surgery itself should not be viewed as a failure. A limited ileocecal resection is more cost effective with equal or better quality of life at 1 year, compared with infliximab therapy, per the randomized LiRIC trial (Lancet Gastroenterol Hepatol 2017;2:785-92).

Therapy is evolving at a rapid pace, while the disease itself is increasing in incidence and prevalence around the world. To truly manage this patient population, we need to have a population-based intervention (diet, predictive biomarkers, etc.) to help reduce the number of people developing IBD, and a better understanding of when and how to use the mechanisms of action we already have to achieve and maintain remission in patients with IBD.
 

Dr. Mahadevan is professor of medicine, University of California at San Francisco Center for Colitis and Crohn’s Disease. She has disclosed receiving grant or research support from Tigenix, Pfizer, Genentech, and Celgene and being a consultant for Gilead, AbbVie, Bristol-Myers Squibb, Janssen, Takeda, and Lilly. Dr. Mahadevan made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

LUGANO, Switzerland – Hot on the heels of the phase 3 ROBUST study showing that adding lenalidomide to standard chemotherapy did not improve outcomes for patients with untreated diffuse large B-cell lymphoma come results of a different study showing a significant benefit with the therapy.

Neil Osterweil/MDedge News

Although, as previously reported, adding lenalidomide (Revlimid) to standard chemotherapy for patients with newly diagnosed ABC-type diffuse large B-cell lymphoma (DLBCL) – the so-called R2-CHOP regimen – did not significantly improve either progression-free or overall survival, compared with R-CHOP alone in ROBUST, results from the randomized phase 2 ECOG-ACRIN 1412 study showed that R2-CHOP was associated with a 34% reduction in the risk of disease progression or death, compared with R-CHOP alone.

“The efficacy endpoints are consistent, with trends toward higher PET complete response rate and improved overall survival with R-squared CHOP,” Grzegorz S. Nowakowski, MD, of the Mayo Clinic, Rochester, Minn., said at the International Conference on Malignant Lymphoma.

So what’s behind the conflicting findings?

Neil Osterweil/MDedge News

The differences between the results of the two studies may be accounted for by the higher lenalidomide dose used in ECOG-ACRIN 1412, the patient populations – all comers in ECOG-ACRIN versus only patients with activated B-cell (ABC) type DLBCL in ROBUST – and by a 10-day shorter median time to treatment in ECOG-ACRIN 1412, said invited discussant Margaret A. Shipp, MD, of the Dana-Farber Cancer Institute in Boston.

The rationale for adding lenalidomide to R-CHOP came from in vitro studies showing antiproliferative and immunomodulatory action of lenalidomide against DLBCL, as well as two proof-of-concept clinical studies (REAL07 and MC078E) indicating efficacy against non-germinal center-like B (GCB) type DLBCL.

In a subanalysis of patients enrolled in MC078E, Dr. Nowakowski and colleagues found that using classification of patients by cell of origin with the NanoString Lymphoma Subtype assay, the addition of lenalidomide to R-CHOP “appears to mitigate the negative impact of an ABC molecular subtype on the outcome.”
 

ECOG-ACRIN 1412 details

Goals of the ECOG-ACRIN 1412 study were to evaluate the effect of lenalidomide both in all DLBCL subtypes and in the ABC subtype, maximize the synergy of the immunomodulator with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) while maintaining R-CHOP dose intensity, and facilitate the enrollment of patients with rapidly progressive disease.

To accomplish the last goal, the study was designed to allow enrollment based on local laboratory findings, scans, and diagnostic pathology, without required identification of the cell of origin. Built in to the design was the plan for final eligibility to be based on central pathology review. In other words, the trial design took into account the likelihood that some enrolled patients would not qualify for eligibility based on later pathology review.

The investigators enrolled 349 adults aged 18 years or older with pathologically confirmed DLBCL (regardless of the cell of origin), stage II bulky to stage IV disease, International Prognostic Index (IPI) scores of 2 or greater, and Eastern Cooperative Oncology Group performance status scores of 2 or less.

The patients were stratified by age (younger than 60 years vs. 60 years and older) and by IPI score (2/3 vs. 4/5), and then randomized to receive either six cycles of R-CHOP or R2-CHOP. Lenalidomide was given in a dose of 25 mg on days 1-10 of each cycle. In contrast, the dose used in ROBUST was 15 mg given on days 1-14 of each cycle.

In ECOG-ACRIN 1412, patients assigned to lenalidomide received mandatory neutropenia prophylaxis with granulocyte-colony stimulating factor.

The time from diagnosis to treatment was a median of 21 days, with only 61 of 280 evaluable patients starting treatment more than 31 days after diagnosis. In ROBUST, the median time to start therapy was 31 days.

Dr. Nowakowski and his colleagues had previously shown that time to treatment is an important prognostic factor in DLBCL.

The efficacy evaluation included 145 patients assigned to R2-CHOP, and 135 assigned to R-CHOP. Primary reasons for exclusion were ineligibity following central pathology review or lack of diagnostic material for review.

After a median follow-up of 2.5 years, R2-CHOP was associated with a 34% improvement in progression-free survival, the primary endpoint (hazard ratio [HR] 0.66, P = .03). The 1-year progression-free survival rates were 83% with R2-CHOP and 73% with R-CHOP. Respective 2-year progression-free survival rates were 76% and 70%.

There was no significant difference, however, in the secondary overall survival endpoints with 1-year and 2-year overall survival of 93% vs. 87% and 86% vs. 80%, respectively.

Similarly, there was no difference in rates of PET-ascertained complete response, at 72% with R2-CHOP and 67% with R-CHOP.

R2-CHOP showed greater benefit across most subgroups, including patients with lower IPI score, patients with bulky disease, patients younger than 60 years, women, and patients with shorter time to treatment. There were also nonsignificant trends hinting at better outcomes with R2-CHOP, regardless of cell of origin.

Toxicities were typical for R-CHOP, although patients on R2-CHOP had significantly higher rates of grade 3 or 4 diarrhea, febrile neutropenia, and thrombocytopenia.

In addition to the trial differences mentioned previously, the differences in outcomes might be explained by the possibility that lenalidomide activity is not restricted to ABC DLBCL, Dr. Shipp said.

“One of the things that’s important to remember about lenalidomide is that it’s an immunomodulating agent and it has also has effects on tumor-infiltrating T cells,” she said.

Differences in response to therapy may also be explained by recent findings showing genetic heterogeneity in transcription-defined ABC DLBCLs, she said.

ECOG-ACRIN 1412 was supported by the National Cancer Institute and by Celgene. Dr. Nowakowski reported consulting/advising for and research funding from Celgene and others. Dr. Shipp reported consulting/advising for Bristol-Myers Squibb, honoraria from BMS and AstraZeneca, and institutional research funding from BMS and Bayer.

SOURCE: Nowakowski GS et al. 15-ICML, Abstract 006.

LUGANO, Switzerland – Hot on the heels of the phase 3 ROBUST study showing that adding lenalidomide to standard chemotherapy did not improve outcomes for patients with untreated diffuse large B-cell lymphoma come results of a different study showing a significant benefit with the therapy.

Neil Osterweil/MDedge News

Although, as previously reported, adding lenalidomide (Revlimid) to standard chemotherapy for patients with newly diagnosed ABC-type diffuse large B-cell lymphoma (DLBCL) – the so-called R2-CHOP regimen – did not significantly improve either progression-free or overall survival, compared with R-CHOP alone in ROBUST, results from the randomized phase 2 ECOG-ACRIN 1412 study showed that R2-CHOP was associated with a 34% reduction in the risk of disease progression or death, compared with R-CHOP alone.

“The efficacy endpoints are consistent, with trends toward higher PET complete response rate and improved overall survival with R-squared CHOP,” Grzegorz S. Nowakowski, MD, of the Mayo Clinic, Rochester, Minn., said at the International Conference on Malignant Lymphoma.

So what’s behind the conflicting findings?

Neil Osterweil/MDedge News

The differences between the results of the two studies may be accounted for by the higher lenalidomide dose used in ECOG-ACRIN 1412, the patient populations – all comers in ECOG-ACRIN versus only patients with activated B-cell (ABC) type DLBCL in ROBUST – and by a 10-day shorter median time to treatment in ECOG-ACRIN 1412, said invited discussant Margaret A. Shipp, MD, of the Dana-Farber Cancer Institute in Boston.

The rationale for adding lenalidomide to R-CHOP came from in vitro studies showing antiproliferative and immunomodulatory action of lenalidomide against DLBCL, as well as two proof-of-concept clinical studies (REAL07 and MC078E) indicating efficacy against non-germinal center-like B (GCB) type DLBCL.

In a subanalysis of patients enrolled in MC078E, Dr. Nowakowski and colleagues found that using classification of patients by cell of origin with the NanoString Lymphoma Subtype assay, the addition of lenalidomide to R-CHOP “appears to mitigate the negative impact of an ABC molecular subtype on the outcome.”
 

ECOG-ACRIN 1412 details

Goals of the ECOG-ACRIN 1412 study were to evaluate the effect of lenalidomide both in all DLBCL subtypes and in the ABC subtype, maximize the synergy of the immunomodulator with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) while maintaining R-CHOP dose intensity, and facilitate the enrollment of patients with rapidly progressive disease.

To accomplish the last goal, the study was designed to allow enrollment based on local laboratory findings, scans, and diagnostic pathology, without required identification of the cell of origin. Built in to the design was the plan for final eligibility to be based on central pathology review. In other words, the trial design took into account the likelihood that some enrolled patients would not qualify for eligibility based on later pathology review.

The investigators enrolled 349 adults aged 18 years or older with pathologically confirmed DLBCL (regardless of the cell of origin), stage II bulky to stage IV disease, International Prognostic Index (IPI) scores of 2 or greater, and Eastern Cooperative Oncology Group performance status scores of 2 or less.

The patients were stratified by age (younger than 60 years vs. 60 years and older) and by IPI score (2/3 vs. 4/5), and then randomized to receive either six cycles of R-CHOP or R2-CHOP. Lenalidomide was given in a dose of 25 mg on days 1-10 of each cycle. In contrast, the dose used in ROBUST was 15 mg given on days 1-14 of each cycle.

In ECOG-ACRIN 1412, patients assigned to lenalidomide received mandatory neutropenia prophylaxis with granulocyte-colony stimulating factor.

The time from diagnosis to treatment was a median of 21 days, with only 61 of 280 evaluable patients starting treatment more than 31 days after diagnosis. In ROBUST, the median time to start therapy was 31 days.

Dr. Nowakowski and his colleagues had previously shown that time to treatment is an important prognostic factor in DLBCL.

The efficacy evaluation included 145 patients assigned to R2-CHOP, and 135 assigned to R-CHOP. Primary reasons for exclusion were ineligibity following central pathology review or lack of diagnostic material for review.

After a median follow-up of 2.5 years, R2-CHOP was associated with a 34% improvement in progression-free survival, the primary endpoint (hazard ratio [HR] 0.66, P = .03). The 1-year progression-free survival rates were 83% with R2-CHOP and 73% with R-CHOP. Respective 2-year progression-free survival rates were 76% and 70%.

There was no significant difference, however, in the secondary overall survival endpoints with 1-year and 2-year overall survival of 93% vs. 87% and 86% vs. 80%, respectively.

Similarly, there was no difference in rates of PET-ascertained complete response, at 72% with R2-CHOP and 67% with R-CHOP.

R2-CHOP showed greater benefit across most subgroups, including patients with lower IPI score, patients with bulky disease, patients younger than 60 years, women, and patients with shorter time to treatment. There were also nonsignificant trends hinting at better outcomes with R2-CHOP, regardless of cell of origin.

Toxicities were typical for R-CHOP, although patients on R2-CHOP had significantly higher rates of grade 3 or 4 diarrhea, febrile neutropenia, and thrombocytopenia.

In addition to the trial differences mentioned previously, the differences in outcomes might be explained by the possibility that lenalidomide activity is not restricted to ABC DLBCL, Dr. Shipp said.

“One of the things that’s important to remember about lenalidomide is that it’s an immunomodulating agent and it has also has effects on tumor-infiltrating T cells,” she said.

Differences in response to therapy may also be explained by recent findings showing genetic heterogeneity in transcription-defined ABC DLBCLs, she said.

ECOG-ACRIN 1412 was supported by the National Cancer Institute and by Celgene. Dr. Nowakowski reported consulting/advising for and research funding from Celgene and others. Dr. Shipp reported consulting/advising for Bristol-Myers Squibb, honoraria from BMS and AstraZeneca, and institutional research funding from BMS and Bayer.

SOURCE: Nowakowski GS et al. 15-ICML, Abstract 006.

LUGANO, Switzerland – Hot on the heels of the phase 3 ROBUST study showing that adding lenalidomide to standard chemotherapy did not improve outcomes for patients with untreated diffuse large B-cell lymphoma come results of a different study showing a significant benefit with the therapy.

Neil Osterweil/MDedge News

Although, as previously reported, adding lenalidomide (Revlimid) to standard chemotherapy for patients with newly diagnosed ABC-type diffuse large B-cell lymphoma (DLBCL) – the so-called R2-CHOP regimen – did not significantly improve either progression-free or overall survival, compared with R-CHOP alone in ROBUST, results from the randomized phase 2 ECOG-ACRIN 1412 study showed that R2-CHOP was associated with a 34% reduction in the risk of disease progression or death, compared with R-CHOP alone.

“The efficacy endpoints are consistent, with trends toward higher PET complete response rate and improved overall survival with R-squared CHOP,” Grzegorz S. Nowakowski, MD, of the Mayo Clinic, Rochester, Minn., said at the International Conference on Malignant Lymphoma.

So what’s behind the conflicting findings?

Neil Osterweil/MDedge News

The differences between the results of the two studies may be accounted for by the higher lenalidomide dose used in ECOG-ACRIN 1412, the patient populations – all comers in ECOG-ACRIN versus only patients with activated B-cell (ABC) type DLBCL in ROBUST – and by a 10-day shorter median time to treatment in ECOG-ACRIN 1412, said invited discussant Margaret A. Shipp, MD, of the Dana-Farber Cancer Institute in Boston.

The rationale for adding lenalidomide to R-CHOP came from in vitro studies showing antiproliferative and immunomodulatory action of lenalidomide against DLBCL, as well as two proof-of-concept clinical studies (REAL07 and MC078E) indicating efficacy against non-germinal center-like B (GCB) type DLBCL.

In a subanalysis of patients enrolled in MC078E, Dr. Nowakowski and colleagues found that using classification of patients by cell of origin with the NanoString Lymphoma Subtype assay, the addition of lenalidomide to R-CHOP “appears to mitigate the negative impact of an ABC molecular subtype on the outcome.”
 

ECOG-ACRIN 1412 details

Goals of the ECOG-ACRIN 1412 study were to evaluate the effect of lenalidomide both in all DLBCL subtypes and in the ABC subtype, maximize the synergy of the immunomodulator with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) while maintaining R-CHOP dose intensity, and facilitate the enrollment of patients with rapidly progressive disease.

To accomplish the last goal, the study was designed to allow enrollment based on local laboratory findings, scans, and diagnostic pathology, without required identification of the cell of origin. Built in to the design was the plan for final eligibility to be based on central pathology review. In other words, the trial design took into account the likelihood that some enrolled patients would not qualify for eligibility based on later pathology review.

The investigators enrolled 349 adults aged 18 years or older with pathologically confirmed DLBCL (regardless of the cell of origin), stage II bulky to stage IV disease, International Prognostic Index (IPI) scores of 2 or greater, and Eastern Cooperative Oncology Group performance status scores of 2 or less.

The patients were stratified by age (younger than 60 years vs. 60 years and older) and by IPI score (2/3 vs. 4/5), and then randomized to receive either six cycles of R-CHOP or R2-CHOP. Lenalidomide was given in a dose of 25 mg on days 1-10 of each cycle. In contrast, the dose used in ROBUST was 15 mg given on days 1-14 of each cycle.

In ECOG-ACRIN 1412, patients assigned to lenalidomide received mandatory neutropenia prophylaxis with granulocyte-colony stimulating factor.

The time from diagnosis to treatment was a median of 21 days, with only 61 of 280 evaluable patients starting treatment more than 31 days after diagnosis. In ROBUST, the median time to start therapy was 31 days.

Dr. Nowakowski and his colleagues had previously shown that time to treatment is an important prognostic factor in DLBCL.

The efficacy evaluation included 145 patients assigned to R2-CHOP, and 135 assigned to R-CHOP. Primary reasons for exclusion were ineligibity following central pathology review or lack of diagnostic material for review.

After a median follow-up of 2.5 years, R2-CHOP was associated with a 34% improvement in progression-free survival, the primary endpoint (hazard ratio [HR] 0.66, P = .03). The 1-year progression-free survival rates were 83% with R2-CHOP and 73% with R-CHOP. Respective 2-year progression-free survival rates were 76% and 70%.

There was no significant difference, however, in the secondary overall survival endpoints with 1-year and 2-year overall survival of 93% vs. 87% and 86% vs. 80%, respectively.

Similarly, there was no difference in rates of PET-ascertained complete response, at 72% with R2-CHOP and 67% with R-CHOP.

R2-CHOP showed greater benefit across most subgroups, including patients with lower IPI score, patients with bulky disease, patients younger than 60 years, women, and patients with shorter time to treatment. There were also nonsignificant trends hinting at better outcomes with R2-CHOP, regardless of cell of origin.

Toxicities were typical for R-CHOP, although patients on R2-CHOP had significantly higher rates of grade 3 or 4 diarrhea, febrile neutropenia, and thrombocytopenia.

In addition to the trial differences mentioned previously, the differences in outcomes might be explained by the possibility that lenalidomide activity is not restricted to ABC DLBCL, Dr. Shipp said.

“One of the things that’s important to remember about lenalidomide is that it’s an immunomodulating agent and it has also has effects on tumor-infiltrating T cells,” she said.

Differences in response to therapy may also be explained by recent findings showing genetic heterogeneity in transcription-defined ABC DLBCLs, she said.

ECOG-ACRIN 1412 was supported by the National Cancer Institute and by Celgene. Dr. Nowakowski reported consulting/advising for and research funding from Celgene and others. Dr. Shipp reported consulting/advising for Bristol-Myers Squibb, honoraria from BMS and AstraZeneca, and institutional research funding from BMS and Bayer.

SOURCE: Nowakowski GS et al. 15-ICML, Abstract 006.

Three main changes characterize the secular trends in the incidence of hepatocellular carcinoma (HCC) in the United States. First, the overall incidence and mortality rates of HCC have been rising for the past 3 decades. Second, Hispanics are disproportionately affected by the HCC increase and have recently surpassed Asian Americans as the racial/ethnic group at highest HCC risk. Third, Southern and Western states have registered higher incidence rates of HCC than did the rest of the country, with Texas having the highest rates.

There are significant racial/ethnic differences in the population distribution of HCC risk factors, notably the disproportionately high prevalence of metabolic syndrome (e.g., obesity, abdominal obesity, and diabetes) and nonalcoholic fatty liver disease (NAFLD) in Hispanics. This observation may explain some of the findings in the secular trends of HCC described above. Most, but not all, studies have reported modest increases in relative risk of HCC in persons with obesity as measured by body mass index. However, studies investigating more specific obesity measures such as obesity in early adulthood or abdominal obesity reported higher and more consistent HCC risk than did those using body mass index. Hispanics have been shown to have a higher proportion of abdominal, especially visceral fat, than African Americans. The prevalence of NAFLD in the United States has doubled over the last 2 decades, and is estimated to affect 15%-20% of adults overall, but up to 30% in adult Texas Hispanics. Recently, a large cohort study including 296,707 patients with NAFLD and an equal number of matched controls without NAFLD from 130 facilities of the Department of Veterans Affairs found that patients with NAFLD had several-fold higher HCC risk than controls. The study also reported that HCC incidence rates for patients with NAFLD ranged from 1.6 to 23.7 per 1000 person-years, with the highest risk among older Hispanic patients with cirrhosis. Approximately 20% of patients with NAFLD and HCC had no evidence of cirrhosis. Lastly, type 2 diabetes, a condition that also is disproportionately higher in Hispanics than in other racial/ethnic groups in the United States has been consistently associated with an approximately twofold increase in the risk of HCC.

Risk factors for cirrhosis and HCC in contemporary clinical practice, and to a lesser extent, in the general population have shifted from active viral hepatitis to resolved hepatitis C infection or adequately suppressed hepatitis B infection as well as alcoholic liver disease and NAFLD. The shift from uncommon risk factors that carry a considerable increased risk of cirrhosis and HCC (active hepatitis C virus, hepatitis B virus) to more common but weaker risk factors (alcohol, NAFLD) is likely to result in a larger pool of chronic liver disease patients at risk for developing cirrhosis and HCC. However, given that the relative risk of HCC is lower with these emerging risk factors, it also will become increasingly difficult to define the highest-risk groups in need of interventions or monitoring. Therefore, there is a clear need for risk-stratification tools for cirrhosis and HCC in patients with HCV and a sustained virologic response, adequate HBV suppression, alcoholic liver disease, and NAFLD.
 

Dr. El-Serag is with the section of gastroenterology and hepatology, department of medicine, Baylor College of Medicine, Houston. Dr. El-Serag made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

Three main changes characterize the secular trends in the incidence of hepatocellular carcinoma (HCC) in the United States. First, the overall incidence and mortality rates of HCC have been rising for the past 3 decades. Second, Hispanics are disproportionately affected by the HCC increase and have recently surpassed Asian Americans as the racial/ethnic group at highest HCC risk. Third, Southern and Western states have registered higher incidence rates of HCC than did the rest of the country, with Texas having the highest rates.

There are significant racial/ethnic differences in the population distribution of HCC risk factors, notably the disproportionately high prevalence of metabolic syndrome (e.g., obesity, abdominal obesity, and diabetes) and nonalcoholic fatty liver disease (NAFLD) in Hispanics. This observation may explain some of the findings in the secular trends of HCC described above. Most, but not all, studies have reported modest increases in relative risk of HCC in persons with obesity as measured by body mass index. However, studies investigating more specific obesity measures such as obesity in early adulthood or abdominal obesity reported higher and more consistent HCC risk than did those using body mass index. Hispanics have been shown to have a higher proportion of abdominal, especially visceral fat, than African Americans. The prevalence of NAFLD in the United States has doubled over the last 2 decades, and is estimated to affect 15%-20% of adults overall, but up to 30% in adult Texas Hispanics. Recently, a large cohort study including 296,707 patients with NAFLD and an equal number of matched controls without NAFLD from 130 facilities of the Department of Veterans Affairs found that patients with NAFLD had several-fold higher HCC risk than controls. The study also reported that HCC incidence rates for patients with NAFLD ranged from 1.6 to 23.7 per 1000 person-years, with the highest risk among older Hispanic patients with cirrhosis. Approximately 20% of patients with NAFLD and HCC had no evidence of cirrhosis. Lastly, type 2 diabetes, a condition that also is disproportionately higher in Hispanics than in other racial/ethnic groups in the United States has been consistently associated with an approximately twofold increase in the risk of HCC.

Risk factors for cirrhosis and HCC in contemporary clinical practice, and to a lesser extent, in the general population have shifted from active viral hepatitis to resolved hepatitis C infection or adequately suppressed hepatitis B infection as well as alcoholic liver disease and NAFLD. The shift from uncommon risk factors that carry a considerable increased risk of cirrhosis and HCC (active hepatitis C virus, hepatitis B virus) to more common but weaker risk factors (alcohol, NAFLD) is likely to result in a larger pool of chronic liver disease patients at risk for developing cirrhosis and HCC. However, given that the relative risk of HCC is lower with these emerging risk factors, it also will become increasingly difficult to define the highest-risk groups in need of interventions or monitoring. Therefore, there is a clear need for risk-stratification tools for cirrhosis and HCC in patients with HCV and a sustained virologic response, adequate HBV suppression, alcoholic liver disease, and NAFLD.
 

Dr. El-Serag is with the section of gastroenterology and hepatology, department of medicine, Baylor College of Medicine, Houston. Dr. El-Serag made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

Three main changes characterize the secular trends in the incidence of hepatocellular carcinoma (HCC) in the United States. First, the overall incidence and mortality rates of HCC have been rising for the past 3 decades. Second, Hispanics are disproportionately affected by the HCC increase and have recently surpassed Asian Americans as the racial/ethnic group at highest HCC risk. Third, Southern and Western states have registered higher incidence rates of HCC than did the rest of the country, with Texas having the highest rates.

There are significant racial/ethnic differences in the population distribution of HCC risk factors, notably the disproportionately high prevalence of metabolic syndrome (e.g., obesity, abdominal obesity, and diabetes) and nonalcoholic fatty liver disease (NAFLD) in Hispanics. This observation may explain some of the findings in the secular trends of HCC described above. Most, but not all, studies have reported modest increases in relative risk of HCC in persons with obesity as measured by body mass index. However, studies investigating more specific obesity measures such as obesity in early adulthood or abdominal obesity reported higher and more consistent HCC risk than did those using body mass index. Hispanics have been shown to have a higher proportion of abdominal, especially visceral fat, than African Americans. The prevalence of NAFLD in the United States has doubled over the last 2 decades, and is estimated to affect 15%-20% of adults overall, but up to 30% in adult Texas Hispanics. Recently, a large cohort study including 296,707 patients with NAFLD and an equal number of matched controls without NAFLD from 130 facilities of the Department of Veterans Affairs found that patients with NAFLD had several-fold higher HCC risk than controls. The study also reported that HCC incidence rates for patients with NAFLD ranged from 1.6 to 23.7 per 1000 person-years, with the highest risk among older Hispanic patients with cirrhosis. Approximately 20% of patients with NAFLD and HCC had no evidence of cirrhosis. Lastly, type 2 diabetes, a condition that also is disproportionately higher in Hispanics than in other racial/ethnic groups in the United States has been consistently associated with an approximately twofold increase in the risk of HCC.

Risk factors for cirrhosis and HCC in contemporary clinical practice, and to a lesser extent, in the general population have shifted from active viral hepatitis to resolved hepatitis C infection or adequately suppressed hepatitis B infection as well as alcoholic liver disease and NAFLD. The shift from uncommon risk factors that carry a considerable increased risk of cirrhosis and HCC (active hepatitis C virus, hepatitis B virus) to more common but weaker risk factors (alcohol, NAFLD) is likely to result in a larger pool of chronic liver disease patients at risk for developing cirrhosis and HCC. However, given that the relative risk of HCC is lower with these emerging risk factors, it also will become increasingly difficult to define the highest-risk groups in need of interventions or monitoring. Therefore, there is a clear need for risk-stratification tools for cirrhosis and HCC in patients with HCV and a sustained virologic response, adequate HBV suppression, alcoholic liver disease, and NAFLD.
 

Dr. El-Serag is with the section of gastroenterology and hepatology, department of medicine, Baylor College of Medicine, Houston. Dr. El-Serag made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

Chronic obstructive pulmonary disease (COPD) is often heterogeneous in its presentation and prognosis, and neither pulmonary function tests nor CT alone are always adequate to characterize a patient’s disease. Combining visual and quantitative information from these clinical tests, however, can allow physicians to more precisely subtype COPD and assess patients’ risk, a study has found.

In a paper published in CHEST, Jinkyeong Park, MD, PhD, of Dongguk University Ilsan Hospital in Goyang, South Korea, and colleagues looked at data from 9,080 subjects enrolled in the COPDGene study, an observational cohort of longtime smokers with and without COPD. By assessing visually defined patterns of emphysema with quantitative imaging features and spirometry data, the researchers identified 10 distinct subtypes of COPD (including no disease) and noted significant differences in mortality and progression among them.

Dr. Park and colleagues found that patients in the subgroups with quantitative but no visual emphysema and those with visual but not quantitative emphysema represented unique groups with mild COPD that were both at risk for progression – but with likely different underlying mechanisms. Current smokers, women, and whites were more common among subjects showing visually defined emphysema without quantitative evidence. “Many of the subjects in the visual-only emphysema subtype have areas of low lung density due to emphysema masked by smoking-induced lung inflammation,” the researchers wrote.

Overall 5-year mortality differed significantly among the groups (P less than .01) and was highest in the three groups with moderate to severe centrilobular emphysema. Patients with paraseptal and moderate to severe centrilobular emphysema showed substantial progression of emphysema over 5 years, compared with individuals with no CT abnormality (P less than .05).

“These results suggest that the combination of visual and quantitative CT features, which may reflect different underlying pathobiological processes in COPD, may provide a superior approach to classify individuals with COPD, compared to the use of visual or quantitative CT features alone,” the researchers wrote.

The study received funding from the National Heart, Lung and Blood Institute. Three of the study’s coauthors reported conflicts of interest in the form of patent applications or financial support from pharmaceutical firms. The COPDGene Project receives pharmaceutical industry and U.S. government support.

SOURCE: Park J et al. CHEST. 2019 Jul 5. doi:10:1016/j.chest.2019.06.15.

Chronic obstructive pulmonary disease (COPD) is often heterogeneous in its presentation and prognosis, and neither pulmonary function tests nor CT alone are always adequate to characterize a patient’s disease. Combining visual and quantitative information from these clinical tests, however, can allow physicians to more precisely subtype COPD and assess patients’ risk, a study has found.

In a paper published in CHEST, Jinkyeong Park, MD, PhD, of Dongguk University Ilsan Hospital in Goyang, South Korea, and colleagues looked at data from 9,080 subjects enrolled in the COPDGene study, an observational cohort of longtime smokers with and without COPD. By assessing visually defined patterns of emphysema with quantitative imaging features and spirometry data, the researchers identified 10 distinct subtypes of COPD (including no disease) and noted significant differences in mortality and progression among them.

Dr. Park and colleagues found that patients in the subgroups with quantitative but no visual emphysema and those with visual but not quantitative emphysema represented unique groups with mild COPD that were both at risk for progression – but with likely different underlying mechanisms. Current smokers, women, and whites were more common among subjects showing visually defined emphysema without quantitative evidence. “Many of the subjects in the visual-only emphysema subtype have areas of low lung density due to emphysema masked by smoking-induced lung inflammation,” the researchers wrote.

Overall 5-year mortality differed significantly among the groups (P less than .01) and was highest in the three groups with moderate to severe centrilobular emphysema. Patients with paraseptal and moderate to severe centrilobular emphysema showed substantial progression of emphysema over 5 years, compared with individuals with no CT abnormality (P less than .05).

“These results suggest that the combination of visual and quantitative CT features, which may reflect different underlying pathobiological processes in COPD, may provide a superior approach to classify individuals with COPD, compared to the use of visual or quantitative CT features alone,” the researchers wrote.

The study received funding from the National Heart, Lung and Blood Institute. Three of the study’s coauthors reported conflicts of interest in the form of patent applications or financial support from pharmaceutical firms. The COPDGene Project receives pharmaceutical industry and U.S. government support.

SOURCE: Park J et al. CHEST. 2019 Jul 5. doi:10:1016/j.chest.2019.06.15.

Chronic obstructive pulmonary disease (COPD) is often heterogeneous in its presentation and prognosis, and neither pulmonary function tests nor CT alone are always adequate to characterize a patient’s disease. Combining visual and quantitative information from these clinical tests, however, can allow physicians to more precisely subtype COPD and assess patients’ risk, a study has found.

In a paper published in CHEST, Jinkyeong Park, MD, PhD, of Dongguk University Ilsan Hospital in Goyang, South Korea, and colleagues looked at data from 9,080 subjects enrolled in the COPDGene study, an observational cohort of longtime smokers with and without COPD. By assessing visually defined patterns of emphysema with quantitative imaging features and spirometry data, the researchers identified 10 distinct subtypes of COPD (including no disease) and noted significant differences in mortality and progression among them.

Dr. Park and colleagues found that patients in the subgroups with quantitative but no visual emphysema and those with visual but not quantitative emphysema represented unique groups with mild COPD that were both at risk for progression – but with likely different underlying mechanisms. Current smokers, women, and whites were more common among subjects showing visually defined emphysema without quantitative evidence. “Many of the subjects in the visual-only emphysema subtype have areas of low lung density due to emphysema masked by smoking-induced lung inflammation,” the researchers wrote.

Overall 5-year mortality differed significantly among the groups (P less than .01) and was highest in the three groups with moderate to severe centrilobular emphysema. Patients with paraseptal and moderate to severe centrilobular emphysema showed substantial progression of emphysema over 5 years, compared with individuals with no CT abnormality (P less than .05).

“These results suggest that the combination of visual and quantitative CT features, which may reflect different underlying pathobiological processes in COPD, may provide a superior approach to classify individuals with COPD, compared to the use of visual or quantitative CT features alone,” the researchers wrote.

The study received funding from the National Heart, Lung and Blood Institute. Three of the study’s coauthors reported conflicts of interest in the form of patent applications or financial support from pharmaceutical firms. The COPDGene Project receives pharmaceutical industry and U.S. government support.

SOURCE: Park J et al. CHEST. 2019 Jul 5. doi:10:1016/j.chest.2019.06.15.