Cardiovascular Medicine and Surgery

Catch 22 of Submassive Pulmonary Emboli

Venous thromboembolism (including deep vein thrombosis (DVT) and pulmonary embolism [PE]) occurs in approximately 1 per 1,000 patients (Piran S, Schulman S. Thromb J. 2016;14[S1]:23) and can be fatal. Pulmonary embolus severity is classified as low risk, intermediate-risk/submassive PE, and massive PE. There is significant controversy about the management of submassive PE, which is defined as PE with right-sided heart strain (elevated troponin or B-type natriuretic peptide, right-axis deviation on ECG, or e

David J. Nagel, MD

Steering Committee Member

Olivier Axler, MD, FCCP

Vice-Chair

Chest Infections

Antibiotic Resistance

One-hundred years ago, infectious diseases caused 5 of the 10 most common causes of deaths in the United States. In 2016, only one infection remained on this list (influenza/pneumonia) (MMWR Morb Mortal Wkly Rep. 2017;66:413).

How medicine has improved with antibiotics. An unfortunate and unintended consequence of widespread antibiotic use has been the progressive resistance to these drugs. It is estimated that, if current trends continue, 10 million lives a year will be at risk from resistant organisms by 2050 (O’Neill, J. (2016). https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf).

Pathogens acquire antibiotic resistance by passing genetic material to one another through plasmids, bacteriophages, or naked DNA. Once acquired, resistance manifests via a number of mechanisms under the stress imposed by antibiotics (Levy SB, et al. Nat Med. 2004;10:S122).

Marc Feinstein, MD, FCCP

Steering Committee Member

Clinical Pulmonary Medicine

COPD and sleep-disordered breathing; A missing comorbid condition

Subjective, as well as objective, sleep complaints are common in patients with COPD (Krachman S, et al. Proc Am Thorac Soc. 2008;5[4]:536), and sleeping difficulties are ranked the third most frequent complaint (behind dyspnea and fatigue) in patients with COPD (Kinsman RA, et al. Chest. 1983;83[5]:755). Also, sleep quality is poor, and patients with moderate to severe COPD may have higher-than-expected incidence of OSA (Soler X, et al. Ann Am Thorac Soc. 2015;12[8]:1219).

Unfortunately, sleep is usually not assessed during a COPD evaluation. Up to 27% of patients with COPD without hypoxia during wakefulness can experience important desaturation during sleep, so called nocturnal oxygen desaturation (NOD) (Fletcher EC, et al. Chest. 1987;92[4]:604), that may lead to pulmonary hypertension (Chaouat A, et a

Xavier Soler, MD, PhD

Steering Committee Member

Interprofessional Team

Finding Home

Outside our internal medicine curriculum, there is no formal pulmonary training or post-masters fellowship in pulmonary medicine for Advanced Practice Providers (APPs). Because of this, APPs are left to their own devices to fill educational gaps. To perform at the level expected by the physicians I work for, journal reviews and memorizing guidelines were not going to be enough. Since there is no formal pulmonary APP society, there were no peers to reach out to either. Off to conferences I went.

At first, I found CHEST daunting. After all, it’s run by the American College of Chest “Physicians,” not Nurse Practitioners. I spent most of the first day with my nametag turned around worried I’d be found out as a nonphysician attendee who snuck in. And then the unthinkable happened, I ran into another unicorn—another APP seeking the same information, only her nametag was turned the right way. The best advice she gave was to attend the Interprofessional NetWork meeting. This was ground zero of the conference as far as I was concerned. There I found myself surrounded by RTs, RNs, NPs, PAs, and yes, even physicians.

Over the years, as I’ve gotten further involved with CHEST NetWorks, I have found from top to bottom CHEST striving to incorporate APPs and advance our education. From including us in the FCCP program, reducing conference pricing for APPs, and focusing this year’s conference theme around being team focused, CHEST is creating a home for APPs.

Corinne Preston Young, FNP, FCCP

Steering Committee Member

Cardiovascular Medicine and Surgery

Catch 22 of Submassive Pulmonary Emboli

Venous thromboembolism (including deep vein thrombosis (DVT) and pulmonary embolism [PE]) occurs in approximately 1 per 1,000 patients (Piran S, Schulman S. Thromb J. 2016;14[S1]:23) and can be fatal. Pulmonary embolus severity is classified as low risk, intermediate-risk/submassive PE, and massive PE. There is significant controversy about the management of submassive PE, which is defined as PE with right-sided heart strain (elevated troponin or B-type natriuretic peptide, right-axis deviation on ECG, or e

David J. Nagel, MD

Steering Committee Member

Olivier Axler, MD, FCCP

Vice-Chair

Chest Infections

Antibiotic Resistance

One-hundred years ago, infectious diseases caused 5 of the 10 most common causes of deaths in the United States. In 2016, only one infection remained on this list (influenza/pneumonia) (MMWR Morb Mortal Wkly Rep. 2017;66:413).

How medicine has improved with antibiotics. An unfortunate and unintended consequence of widespread antibiotic use has been the progressive resistance to these drugs. It is estimated that, if current trends continue, 10 million lives a year will be at risk from resistant organisms by 2050 (O’Neill, J. (2016). https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf).

Pathogens acquire antibiotic resistance by passing genetic material to one another through plasmids, bacteriophages, or naked DNA. Once acquired, resistance manifests via a number of mechanisms under the stress imposed by antibiotics (Levy SB, et al. Nat Med. 2004;10:S122).

Marc Feinstein, MD, FCCP

Steering Committee Member

Clinical Pulmonary Medicine

COPD and sleep-disordered breathing; A missing comorbid condition

Subjective, as well as objective, sleep complaints are common in patients with COPD (Krachman S, et al. Proc Am Thorac Soc. 2008;5[4]:536), and sleeping difficulties are ranked the third most frequent complaint (behind dyspnea and fatigue) in patients with COPD (Kinsman RA, et al. Chest. 1983;83[5]:755). Also, sleep quality is poor, and patients with moderate to severe COPD may have higher-than-expected incidence of OSA (Soler X, et al. Ann Am Thorac Soc. 2015;12[8]:1219).

Unfortunately, sleep is usually not assessed during a COPD evaluation. Up to 27% of patients with COPD without hypoxia during wakefulness can experience important desaturation during sleep, so called nocturnal oxygen desaturation (NOD) (Fletcher EC, et al. Chest. 1987;92[4]:604), that may lead to pulmonary hypertension (Chaouat A, et a

Xavier Soler, MD, PhD

Steering Committee Member

Interprofessional Team

Finding Home

Outside our internal medicine curriculum, there is no formal pulmonary training or post-masters fellowship in pulmonary medicine for Advanced Practice Providers (APPs). Because of this, APPs are left to their own devices to fill educational gaps. To perform at the level expected by the physicians I work for, journal reviews and memorizing guidelines were not going to be enough. Since there is no formal pulmonary APP society, there were no peers to reach out to either. Off to conferences I went.

At first, I found CHEST daunting. After all, it’s run by the American College of Chest “Physicians,” not Nurse Practitioners. I spent most of the first day with my nametag turned around worried I’d be found out as a nonphysician attendee who snuck in. And then the unthinkable happened, I ran into another unicorn—another APP seeking the same information, only her nametag was turned the right way. The best advice she gave was to attend the Interprofessional NetWork meeting. This was ground zero of the conference as far as I was concerned. There I found myself surrounded by RTs, RNs, NPs, PAs, and yes, even physicians.

Over the years, as I’ve gotten further involved with CHEST NetWorks, I have found from top to bottom CHEST striving to incorporate APPs and advance our education. From including us in the FCCP program, reducing conference pricing for APPs, and focusing this year’s conference theme around being team focused, CHEST is creating a home for APPs.

Corinne Preston Young, FNP, FCCP

Steering Committee Member

Cardiovascular Medicine and Surgery

Catch 22 of Submassive Pulmonary Emboli

Venous thromboembolism (including deep vein thrombosis (DVT) and pulmonary embolism [PE]) occurs in approximately 1 per 1,000 patients (Piran S, Schulman S. Thromb J. 2016;14[S1]:23) and can be fatal. Pulmonary embolus severity is classified as low risk, intermediate-risk/submassive PE, and massive PE. There is significant controversy about the management of submassive PE, which is defined as PE with right-sided heart strain (elevated troponin or B-type natriuretic peptide, right-axis deviation on ECG, or e

David J. Nagel, MD

Steering Committee Member

Olivier Axler, MD, FCCP

Vice-Chair

Chest Infections

Antibiotic Resistance

One-hundred years ago, infectious diseases caused 5 of the 10 most common causes of deaths in the United States. In 2016, only one infection remained on this list (influenza/pneumonia) (MMWR Morb Mortal Wkly Rep. 2017;66:413).

How medicine has improved with antibiotics. An unfortunate and unintended consequence of widespread antibiotic use has been the progressive resistance to these drugs. It is estimated that, if current trends continue, 10 million lives a year will be at risk from resistant organisms by 2050 (O’Neill, J. (2016). https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf).

Pathogens acquire antibiotic resistance by passing genetic material to one another through plasmids, bacteriophages, or naked DNA. Once acquired, resistance manifests via a number of mechanisms under the stress imposed by antibiotics (Levy SB, et al. Nat Med. 2004;10:S122).

Marc Feinstein, MD, FCCP

Steering Committee Member

Clinical Pulmonary Medicine

COPD and sleep-disordered breathing; A missing comorbid condition

Subjective, as well as objective, sleep complaints are common in patients with COPD (Krachman S, et al. Proc Am Thorac Soc. 2008;5[4]:536), and sleeping difficulties are ranked the third most frequent complaint (behind dyspnea and fatigue) in patients with COPD (Kinsman RA, et al. Chest. 1983;83[5]:755). Also, sleep quality is poor, and patients with moderate to severe COPD may have higher-than-expected incidence of OSA (Soler X, et al. Ann Am Thorac Soc. 2015;12[8]:1219).

Unfortunately, sleep is usually not assessed during a COPD evaluation. Up to 27% of patients with COPD without hypoxia during wakefulness can experience important desaturation during sleep, so called nocturnal oxygen desaturation (NOD) (Fletcher EC, et al. Chest. 1987;92[4]:604), that may lead to pulmonary hypertension (Chaouat A, et a

Xavier Soler, MD, PhD

Steering Committee Member

Interprofessional Team

Finding Home

Outside our internal medicine curriculum, there is no formal pulmonary training or post-masters fellowship in pulmonary medicine for Advanced Practice Providers (APPs). Because of this, APPs are left to their own devices to fill educational gaps. To perform at the level expected by the physicians I work for, journal reviews and memorizing guidelines were not going to be enough. Since there is no formal pulmonary APP society, there were no peers to reach out to either. Off to conferences I went.

At first, I found CHEST daunting. After all, it’s run by the American College of Chest “Physicians,” not Nurse Practitioners. I spent most of the first day with my nametag turned around worried I’d be found out as a nonphysician attendee who snuck in. And then the unthinkable happened, I ran into another unicorn—another APP seeking the same information, only her nametag was turned the right way. The best advice she gave was to attend the Interprofessional NetWork meeting. This was ground zero of the conference as far as I was concerned. There I found myself surrounded by RTs, RNs, NPs, PAs, and yes, even physicians.

Over the years, as I’ve gotten further involved with CHEST NetWorks, I have found from top to bottom CHEST striving to incorporate APPs and advance our education. From including us in the FCCP program, reducing conference pricing for APPs, and focusing this year’s conference theme around being team focused, CHEST is creating a home for APPs.

Corinne Preston Young, FNP, FCCP

Steering Committee Member

Partnering with like-minded advocates and organizations strengthens our collective voice to improve patient outcomes. We choose to partner with others who share our values in creating sustainable, long-lasting change by engaging clinicians, patients, caregivers, and the public on the importance of understanding lung health.

Pulmonary Fibrosis Foundation

Allergy & Asthma Network

Over the past 2 years, our relationship with the Allergy & Asthma Network (AAN) has grown to include collaborative disease awareness campaigns, co-branded and co-created patient education materials in asthma and COPD, and an exciting expansion of the platforms we utilize to reach patients. Partnering with the AAN has allowed us to reach new audiences and bring asthma and COPD education to local communities with opportunities, including:

• A Lifetime television segment on Access Health that focuses on asthma education;
• Co-hosted asthma Twitter chats reaching thousands of clinicians and patients; and
• “The Air We Breathe,” an Atlantic Live Summit in Chicago which focused on the relationship between air quality and respiratory health.

COPD Foundation

The COPD Foundation, along with Allergy & Asthma Network, have partnered with us to support our Lung Health Experience, a lung health expo touring Oklahoma City, Nashville, Chicago, and Toronto in 2017. The Lung Health Experience focuses on bringing lung health experts to the public in a comfortable, relaxed, and fun setting. The COPD Foundation and AAN have attended these events to provide the public with educational materials on lung diseases, which support the spirometry screenings performed by local respiratory therapists. We thank the Allergy & Asthma Network and the COPD Foundation for their outstanding support.

It is with these and many other partnerships that the CHEST Foundation is able to elevate its mission to champion lung health and provide local communities with an opportunity to interact with clinicians and physicians outside of a hospital setting. These experiences and collaborations are the key to strengthening the patient and clinician conversation and bridging the gap to improve patient care and outcomes.

Partnering with like-minded advocates and organizations strengthens our collective voice to improve patient outcomes. We choose to partner with others who share our values in creating sustainable, long-lasting change by engaging clinicians, patients, caregivers, and the public on the importance of understanding lung health.

Pulmonary Fibrosis Foundation

Allergy & Asthma Network

Over the past 2 years, our relationship with the Allergy & Asthma Network (AAN) has grown to include collaborative disease awareness campaigns, co-branded and co-created patient education materials in asthma and COPD, and an exciting expansion of the platforms we utilize to reach patients. Partnering with the AAN has allowed us to reach new audiences and bring asthma and COPD education to local communities with opportunities, including:

• A Lifetime television segment on Access Health that focuses on asthma education;
• Co-hosted asthma Twitter chats reaching thousands of clinicians and patients; and
• “The Air We Breathe,” an Atlantic Live Summit in Chicago which focused on the relationship between air quality and respiratory health.

COPD Foundation

The COPD Foundation, along with Allergy & Asthma Network, have partnered with us to support our Lung Health Experience, a lung health expo touring Oklahoma City, Nashville, Chicago, and Toronto in 2017. The Lung Health Experience focuses on bringing lung health experts to the public in a comfortable, relaxed, and fun setting. The COPD Foundation and AAN have attended these events to provide the public with educational materials on lung diseases, which support the spirometry screenings performed by local respiratory therapists. We thank the Allergy & Asthma Network and the COPD Foundation for their outstanding support.

It is with these and many other partnerships that the CHEST Foundation is able to elevate its mission to champion lung health and provide local communities with an opportunity to interact with clinicians and physicians outside of a hospital setting. These experiences and collaborations are the key to strengthening the patient and clinician conversation and bridging the gap to improve patient care and outcomes.

Partnering with like-minded advocates and organizations strengthens our collective voice to improve patient outcomes. We choose to partner with others who share our values in creating sustainable, long-lasting change by engaging clinicians, patients, caregivers, and the public on the importance of understanding lung health.

Pulmonary Fibrosis Foundation

Allergy & Asthma Network

Over the past 2 years, our relationship with the Allergy & Asthma Network (AAN) has grown to include collaborative disease awareness campaigns, co-branded and co-created patient education materials in asthma and COPD, and an exciting expansion of the platforms we utilize to reach patients. Partnering with the AAN has allowed us to reach new audiences and bring asthma and COPD education to local communities with opportunities, including:

• A Lifetime television segment on Access Health that focuses on asthma education;
• Co-hosted asthma Twitter chats reaching thousands of clinicians and patients; and
• “The Air We Breathe,” an Atlantic Live Summit in Chicago which focused on the relationship between air quality and respiratory health.

COPD Foundation

The COPD Foundation, along with Allergy & Asthma Network, have partnered with us to support our Lung Health Experience, a lung health expo touring Oklahoma City, Nashville, Chicago, and Toronto in 2017. The Lung Health Experience focuses on bringing lung health experts to the public in a comfortable, relaxed, and fun setting. The COPD Foundation and AAN have attended these events to provide the public with educational materials on lung diseases, which support the spirometry screenings performed by local respiratory therapists. We thank the Allergy & Asthma Network and the COPD Foundation for their outstanding support.

It is with these and many other partnerships that the CHEST Foundation is able to elevate its mission to champion lung health and provide local communities with an opportunity to interact with clinicians and physicians outside of a hospital setting. These experiences and collaborations are the key to strengthening the patient and clinician conversation and bridging the gap to improve patient care and outcomes.

The Global Impact of Respiratory Disease – Second Edition was released by the Forum of International Respiratory Societies (FIRS) at the World Health Assembly May 25, 2017, in Geneva, Switzerland, calling attention to the global burden of lung disease and the benefits of prevention and clean air.

We often take our breathing and our respiratory health for granted, but respiratory diseases are a leading cause of death and disability in the world. Sixty-five million people suffer from COPD, and 3 million die of it each year, now making it the third leading cause of death worldwide.^1,2 Asthma affects 334 million people in the world and is the most common chronic disease of childhood.³ Pneumonia kills millions of people annually and is a leading cause of death among children under 5 years old.⁴ Over 10 million people develop TB, and 1.4 million die of it each year, making it the most common deadly infectious disease.⁵ Lung cancer kills 1.6 million people each year and is the most deadly cancer.⁶ Globally, at least 2 billion people are exposed to indoor toxic smoke, 1 billion inhale outdoor pollutant air, and 1 billion are exposed to tobacco smoke. Many of us, and the world, are naïve to these staggering realities.

The American College of Chest Physicians® (CHEST), together with FIRS, is working hard to change these realities. CHEST, and our more than 19,000 members around the world, want a better future, one that has less suffering. We want a future that enables and allows everyone to breathe freely.

The 2017 Global Impact of Respiratory Disease report objectively speaks to these issues and outlines an eight-step action plan to impact these serious concerns. It highlights the importance of prevention, control, and cure of these diseases and announces that promotion of respiratory health must be a top priority for health-care systems and decision-makers. In emphasizing that these goals are achievable, it also highlights the reality that the prevention and cure of respiratory diseases are among the most cost-effective health interventions available – a “best-buy” in the view of the World Health Organization (WHO). In addition to reducing so much suffering, investment in respiratory health will pay manifold dividends in longevity, healthy living days, and national economies.

Darcy Marciniuk, MD, FCCP, FRCPC, and Co-Chair of the Report notes, “The Global Impact of Respiratory Disease” report calls attention to the importance of respiratory health in the world. The report and these efforts are required to ensure respiratory health becomes a top priority in global decision-making.”

In addition to focusing attention to the importance of respiratory health in the world and ensuring it becomes a global priority, the 2017 Global Impact of Respiratory Disease report also includes practical information for our members. The report summarizes the current state of our understanding with the “Big 5”: COPD, asthma, pneumonia, lung cancer, and TB, as well as with the environment and clean air, sleep-disordered breathing, pulmonary hypertension, and pulmonary embolism. It highlights key controllable factors, such as a reduction in tobacco smoking and improvement in air quality, which includes reduction in second-hand tobacco smoke, smoke from indoor fire, and unhealthy public and workplace air. The report underlines the value of trained health-care professionals and the need for health-care systems and policies to support those trained professionals. Finally, it emphasizes the reality that investment in respiratory research is more than the hope for today – it is the promise and a genuine commitment for tomorrow. CHEST’s involvement in this important project is only one component of our global engagement and impact. We support and help to educate lung specialists and health-care teams, no matter where they live and work. Our journal CHEST®, and other education offerings, are used every day and in every part of the world. The American College of Chest Physicians® focuses on the prevention, diagnosis, and treatment of chest diseases by providing innovative education and advancing best patient outcomes around the globe.
 

About the Forum of International Respiratory Societies (FIRS) Formed in 2001, the Forum of International Respiratory Societies (FIRS) is composed of the leading international respiratory societies, with more than 70,000 members who devote their working lives to respiratory health and disease. The goal of FIRS is to speak with one voice in promoting respiratory health worldwide and to call for action to reduce, prevent, cure, and control the terrible burden of respiratory disease.

References

1. World Health Organization. Global surveillance, prevention and control of chronic respiratory diseases, a comprehensive approach. 2007.

2. Burney PG, Patel J, Newson R, et al. Global and regional trends in COPD mortality, 1990-2010. Eur Respir J. 2015;45(5):1239-47.

3. International Study of Asthma and Allergies in Childhood (ISAAC). Global Asthma Report. 2014.

4. World Health Organization. Pneumonia: the forgotten killer of children. Geneva: World Health Organization; 2006.

5. World Health Organization. Global Tuberculosis Report 2016. Geneva: World Health Organization; 2016.

6. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108.

The Global Impact of Respiratory Disease – Second Edition was released by the Forum of International Respiratory Societies (FIRS) at the World Health Assembly May 25, 2017, in Geneva, Switzerland, calling attention to the global burden of lung disease and the benefits of prevention and clean air.

We often take our breathing and our respiratory health for granted, but respiratory diseases are a leading cause of death and disability in the world. Sixty-five million people suffer from COPD, and 3 million die of it each year, now making it the third leading cause of death worldwide.^1,2 Asthma affects 334 million people in the world and is the most common chronic disease of childhood.³ Pneumonia kills millions of people annually and is a leading cause of death among children under 5 years old.⁴ Over 10 million people develop TB, and 1.4 million die of it each year, making it the most common deadly infectious disease.⁵ Lung cancer kills 1.6 million people each year and is the most deadly cancer.⁶ Globally, at least 2 billion people are exposed to indoor toxic smoke, 1 billion inhale outdoor pollutant air, and 1 billion are exposed to tobacco smoke. Many of us, and the world, are naïve to these staggering realities.

The American College of Chest Physicians® (CHEST), together with FIRS, is working hard to change these realities. CHEST, and our more than 19,000 members around the world, want a better future, one that has less suffering. We want a future that enables and allows everyone to breathe freely.

The 2017 Global Impact of Respiratory Disease report objectively speaks to these issues and outlines an eight-step action plan to impact these serious concerns. It highlights the importance of prevention, control, and cure of these diseases and announces that promotion of respiratory health must be a top priority for health-care systems and decision-makers. In emphasizing that these goals are achievable, it also highlights the reality that the prevention and cure of respiratory diseases are among the most cost-effective health interventions available – a “best-buy” in the view of the World Health Organization (WHO). In addition to reducing so much suffering, investment in respiratory health will pay manifold dividends in longevity, healthy living days, and national economies.

Darcy Marciniuk, MD, FCCP, FRCPC, and Co-Chair of the Report notes, “The Global Impact of Respiratory Disease” report calls attention to the importance of respiratory health in the world. The report and these efforts are required to ensure respiratory health becomes a top priority in global decision-making.”

In addition to focusing attention to the importance of respiratory health in the world and ensuring it becomes a global priority, the 2017 Global Impact of Respiratory Disease report also includes practical information for our members. The report summarizes the current state of our understanding with the “Big 5”: COPD, asthma, pneumonia, lung cancer, and TB, as well as with the environment and clean air, sleep-disordered breathing, pulmonary hypertension, and pulmonary embolism. It highlights key controllable factors, such as a reduction in tobacco smoking and improvement in air quality, which includes reduction in second-hand tobacco smoke, smoke from indoor fire, and unhealthy public and workplace air. The report underlines the value of trained health-care professionals and the need for health-care systems and policies to support those trained professionals. Finally, it emphasizes the reality that investment in respiratory research is more than the hope for today – it is the promise and a genuine commitment for tomorrow. CHEST’s involvement in this important project is only one component of our global engagement and impact. We support and help to educate lung specialists and health-care teams, no matter where they live and work. Our journal CHEST®, and other education offerings, are used every day and in every part of the world. The American College of Chest Physicians® focuses on the prevention, diagnosis, and treatment of chest diseases by providing innovative education and advancing best patient outcomes around the globe.
 

About the Forum of International Respiratory Societies (FIRS) Formed in 2001, the Forum of International Respiratory Societies (FIRS) is composed of the leading international respiratory societies, with more than 70,000 members who devote their working lives to respiratory health and disease. The goal of FIRS is to speak with one voice in promoting respiratory health worldwide and to call for action to reduce, prevent, cure, and control the terrible burden of respiratory disease.

References

1. World Health Organization. Global surveillance, prevention and control of chronic respiratory diseases, a comprehensive approach. 2007.

2. Burney PG, Patel J, Newson R, et al. Global and regional trends in COPD mortality, 1990-2010. Eur Respir J. 2015;45(5):1239-47.

3. International Study of Asthma and Allergies in Childhood (ISAAC). Global Asthma Report. 2014.

4. World Health Organization. Pneumonia: the forgotten killer of children. Geneva: World Health Organization; 2006.

5. World Health Organization. Global Tuberculosis Report 2016. Geneva: World Health Organization; 2016.

6. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108.

The Global Impact of Respiratory Disease – Second Edition was released by the Forum of International Respiratory Societies (FIRS) at the World Health Assembly May 25, 2017, in Geneva, Switzerland, calling attention to the global burden of lung disease and the benefits of prevention and clean air.

We often take our breathing and our respiratory health for granted, but respiratory diseases are a leading cause of death and disability in the world. Sixty-five million people suffer from COPD, and 3 million die of it each year, now making it the third leading cause of death worldwide.^1,2 Asthma affects 334 million people in the world and is the most common chronic disease of childhood.³ Pneumonia kills millions of people annually and is a leading cause of death among children under 5 years old.⁴ Over 10 million people develop TB, and 1.4 million die of it each year, making it the most common deadly infectious disease.⁵ Lung cancer kills 1.6 million people each year and is the most deadly cancer.⁶ Globally, at least 2 billion people are exposed to indoor toxic smoke, 1 billion inhale outdoor pollutant air, and 1 billion are exposed to tobacco smoke. Many of us, and the world, are naïve to these staggering realities.

The American College of Chest Physicians® (CHEST), together with FIRS, is working hard to change these realities. CHEST, and our more than 19,000 members around the world, want a better future, one that has less suffering. We want a future that enables and allows everyone to breathe freely.

The 2017 Global Impact of Respiratory Disease report objectively speaks to these issues and outlines an eight-step action plan to impact these serious concerns. It highlights the importance of prevention, control, and cure of these diseases and announces that promotion of respiratory health must be a top priority for health-care systems and decision-makers. In emphasizing that these goals are achievable, it also highlights the reality that the prevention and cure of respiratory diseases are among the most cost-effective health interventions available – a “best-buy” in the view of the World Health Organization (WHO). In addition to reducing so much suffering, investment in respiratory health will pay manifold dividends in longevity, healthy living days, and national economies.

Darcy Marciniuk, MD, FCCP, FRCPC, and Co-Chair of the Report notes, “The Global Impact of Respiratory Disease” report calls attention to the importance of respiratory health in the world. The report and these efforts are required to ensure respiratory health becomes a top priority in global decision-making.”

In addition to focusing attention to the importance of respiratory health in the world and ensuring it becomes a global priority, the 2017 Global Impact of Respiratory Disease report also includes practical information for our members. The report summarizes the current state of our understanding with the “Big 5”: COPD, asthma, pneumonia, lung cancer, and TB, as well as with the environment and clean air, sleep-disordered breathing, pulmonary hypertension, and pulmonary embolism. It highlights key controllable factors, such as a reduction in tobacco smoking and improvement in air quality, which includes reduction in second-hand tobacco smoke, smoke from indoor fire, and unhealthy public and workplace air. The report underlines the value of trained health-care professionals and the need for health-care systems and policies to support those trained professionals. Finally, it emphasizes the reality that investment in respiratory research is more than the hope for today – it is the promise and a genuine commitment for tomorrow. CHEST’s involvement in this important project is only one component of our global engagement and impact. We support and help to educate lung specialists and health-care teams, no matter where they live and work. Our journal CHEST®, and other education offerings, are used every day and in every part of the world. The American College of Chest Physicians® focuses on the prevention, diagnosis, and treatment of chest diseases by providing innovative education and advancing best patient outcomes around the globe.
 

About the Forum of International Respiratory Societies (FIRS) Formed in 2001, the Forum of International Respiratory Societies (FIRS) is composed of the leading international respiratory societies, with more than 70,000 members who devote their working lives to respiratory health and disease. The goal of FIRS is to speak with one voice in promoting respiratory health worldwide and to call for action to reduce, prevent, cure, and control the terrible burden of respiratory disease.

References

1. World Health Organization. Global surveillance, prevention and control of chronic respiratory diseases, a comprehensive approach. 2007.

2. Burney PG, Patel J, Newson R, et al. Global and regional trends in COPD mortality, 1990-2010. Eur Respir J. 2015;45(5):1239-47.

3. International Study of Asthma and Allergies in Childhood (ISAAC). Global Asthma Report. 2014.

4. World Health Organization. Pneumonia: the forgotten killer of children. Geneva: World Health Organization; 2006.

5. World Health Organization. Global Tuberculosis Report 2016. Geneva: World Health Organization; 2016.

6. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108.

WASHINGTON – Making health care–related decisions for relatives in the ICU heightens an individual’s risk for psychological stress, a new study showed.

While 90% of patients admitted to the ICU lack decision capacity, only 20%-29% of the U.S. population has written advanced directives. Therefore, most often, family members are called upon to make decisions for ICU patients’ care.

Mollie Kalaycio/Frontline Medical News

[email protected]

WASHINGTON – Making health care–related decisions for relatives in the ICU heightens an individual’s risk for psychological stress, a new study showed.

While 90% of patients admitted to the ICU lack decision capacity, only 20%-29% of the U.S. population has written advanced directives. Therefore, most often, family members are called upon to make decisions for ICU patients’ care.

Mollie Kalaycio/Frontline Medical News

[email protected]

WASHINGTON – Making health care–related decisions for relatives in the ICU heightens an individual’s risk for psychological stress, a new study showed.

While 90% of patients admitted to the ICU lack decision capacity, only 20%-29% of the U.S. population has written advanced directives. Therefore, most often, family members are called upon to make decisions for ICU patients’ care.

Mollie Kalaycio/Frontline Medical News

[email protected]

Editor’s note: “Everything We Say and Do” is an informational series developed by SHM’s Patient Experience Committee to provide readers with thoughtful and actionable communication tactics that have great potential to positively impact patients’ experience of care. Each article will focus on how the contributor applies one or more of the “key communication” tactics in practice to maintain provider accountability for “everything we say and do that affects our patients’ thoughts, feelings, and well-being.”

What I say and do

I always ensure at the end of my visit with a patient and their family that they know when to expect me to return to see their child again.

Why I do it

One of the biggest frustrations I hear from families pertains to the discharge process. In talking with families, they want to know the approximate time for discharge. Often, during morning rounds, we mention that the patient may be able to go home later in the day and we say that we will come in again later to check on them. However, unless we give families a time frame for when we will come back and do that check, they are left waiting without any clear expectations.

How I do it

One of our goals during morning family-centered rounds is to discuss discharge for every patient, every day. Along with discussing the possibility of going home, we try to give the family goals that they can work on throughout the day that are tied to discharge – for example, the approximate by-mouth intake for a toddler admitted for gastroenteritis and dehydration.

I also give the family an approximate time when either I or the resident team will come back to see if they have achieved this goal. This may be either late afternoon or first thing in the morning if we are planning an early-morning discharge before rounds. The families seem to find this helpful because they are not tied to the room all day waiting for the doctor to come back.

I also make sure that the families know they can contact their nurse any time if they need to see any of the doctors sooner than we planned. I let them know that a physician is here on the floor 24 hours a day and that the nurses can easily reach us at any time if they have further concerns. In my experience, this is reassuring to our families.
 

Christine Hrach is a pediatric hospitalist at Washington University School of Medicine in St. Louis.

Editor’s note: “Everything We Say and Do” is an informational series developed by SHM’s Patient Experience Committee to provide readers with thoughtful and actionable communication tactics that have great potential to positively impact patients’ experience of care. Each article will focus on how the contributor applies one or more of the “key communication” tactics in practice to maintain provider accountability for “everything we say and do that affects our patients’ thoughts, feelings, and well-being.”

What I say and do

I always ensure at the end of my visit with a patient and their family that they know when to expect me to return to see their child again.

Why I do it

One of the biggest frustrations I hear from families pertains to the discharge process. In talking with families, they want to know the approximate time for discharge. Often, during morning rounds, we mention that the patient may be able to go home later in the day and we say that we will come in again later to check on them. However, unless we give families a time frame for when we will come back and do that check, they are left waiting without any clear expectations.

How I do it

One of our goals during morning family-centered rounds is to discuss discharge for every patient, every day. Along with discussing the possibility of going home, we try to give the family goals that they can work on throughout the day that are tied to discharge – for example, the approximate by-mouth intake for a toddler admitted for gastroenteritis and dehydration.

I also give the family an approximate time when either I or the resident team will come back to see if they have achieved this goal. This may be either late afternoon or first thing in the morning if we are planning an early-morning discharge before rounds. The families seem to find this helpful because they are not tied to the room all day waiting for the doctor to come back.

I also make sure that the families know they can contact their nurse any time if they need to see any of the doctors sooner than we planned. I let them know that a physician is here on the floor 24 hours a day and that the nurses can easily reach us at any time if they have further concerns. In my experience, this is reassuring to our families.
 

Christine Hrach is a pediatric hospitalist at Washington University School of Medicine in St. Louis.

Editor’s note: “Everything We Say and Do” is an informational series developed by SHM’s Patient Experience Committee to provide readers with thoughtful and actionable communication tactics that have great potential to positively impact patients’ experience of care. Each article will focus on how the contributor applies one or more of the “key communication” tactics in practice to maintain provider accountability for “everything we say and do that affects our patients’ thoughts, feelings, and well-being.”

What I say and do

I always ensure at the end of my visit with a patient and their family that they know when to expect me to return to see their child again.

Why I do it

One of the biggest frustrations I hear from families pertains to the discharge process. In talking with families, they want to know the approximate time for discharge. Often, during morning rounds, we mention that the patient may be able to go home later in the day and we say that we will come in again later to check on them. However, unless we give families a time frame for when we will come back and do that check, they are left waiting without any clear expectations.

How I do it

One of our goals during morning family-centered rounds is to discuss discharge for every patient, every day. Along with discussing the possibility of going home, we try to give the family goals that they can work on throughout the day that are tied to discharge – for example, the approximate by-mouth intake for a toddler admitted for gastroenteritis and dehydration.

I also give the family an approximate time when either I or the resident team will come back to see if they have achieved this goal. This may be either late afternoon or first thing in the morning if we are planning an early-morning discharge before rounds. The families seem to find this helpful because they are not tied to the room all day waiting for the doctor to come back.

I also make sure that the families know they can contact their nurse any time if they need to see any of the doctors sooner than we planned. I let them know that a physician is here on the floor 24 hours a day and that the nurses can easily reach us at any time if they have further concerns. In my experience, this is reassuring to our families.
 

Christine Hrach is a pediatric hospitalist at Washington University School of Medicine in St. Louis.

SAN FRANCISCO – Most of the pediatric hoarding literature focuses on hoarding accompanied by obsessive-compulsive disorder. But, “I want to highlight that [attention-deficit/hyperactivity disorder] is across the board something that seems to come up in child hoarding behaviors quite a bit, mirroring the adult literature, which is that hoarding behavior may be much more strongly associated with ADHD than it is with OCD,” Jennifer M. Park, PhD, said at the annual conference of the Anxiety and Depression Association of America.

Multiple studies have established that the prevalence of child hoarding is 2%-3.7%. Onset is typically at age 11-15 years. The course is chronic, and it’s a condition that typically exacerbates over time.

“A lot of the adult literature has shown that hoarding behavior actually starts in childhood. In many retrospective reports, adults say, ‘I’ve had these problems ever since I was a kid,’ ” according to Dr. Park, a psychologist affiliated with Stanford (Calif.) University.

Yet childhood hoarding is not widely perceived as problematic. Indeed, many parents and clinicians view it as developmentally appropriate. That’s to a great extent because the presentation of child hoarding behavior often is very different from and less disturbing than adult hoarding for the obvious reason that parents can limit the amount of clutter in the home.

“I have a bunch of kids who have quite significant hoarding behavior, but the parents are really on top of making sure all of that is left in the closet or within the child’s playroom, or maybe a certain section of the house,” Dr. Park said. “They’re able to keep it contained.”

Also, children and young adolescents lack the resources to accumulate massive clutter. They can’t drive, and have little or no money, so they can’t go on compulsive shopping sprees. “What I have seen in the kids that I work with is they make up for that by collecting things like paper and sticks, rocks, wrappers – anything that might be free, or knickknacks they can pick up along the way,” she said.

The cognitive-behavioral model of hoarding was first described 2 decades ago. It names three main factors as key to maintaining hoarding behaviors: emotional attachment and beliefs associated with one’s possessions, often including anthropomorphization; avoidance behaviors due to severe distress at the prospect of discarding stuff; and information-processing deficits.

“The idea here is that deficits in executive function – things like planning, organization, and inhibition – these are known in an extensive literature to be really strongly associated with ADHD, and executive function deficits link well with hoarding disorder as well,” Dr. Park continued.

Dr. Park was the first author of a recent multicenter study of 431 youths aged 6-17 diagnosed with OCD. They were participants in the OCD Collaborative Genetics Study and the OCD Collaborative Genetics Association Study, during which they completed the Behavior Rating Inventory of Executive Functioning (BRIEF) and the Hoarding Rating Scale–Interview. Clinically significant levels of hoarding compulsions were identified in 113 subjects. Compared with the group with OCD but not hoarding, the OCD/hoarding group had significantly lower scores – meaning problematic deficits – on nearly all of the executive function subscales on the BRIEF, including working memory, emotional control, and planning/organization.

The two groups did not differ significantly in the prevalence of full DSM-IV ADHD. But the hoarding group had significantly more inattention and hyperactivity symptoms, and in a multivariate analysis adjusted for age, sex, and ADHD symptoms, deficits in executive function as measured on the BRIEF instrument were the strongest predictor of hoarding severity in the study population (J Psychiatr Res. 2016 Nov;82:141-8).

In another study by Dr. Park and her coinvestigators involving 99 youth diagnosed with ADHD, the severity of inattention and hyperactivity/impulsivity predicted clinically significant hoarding, whereas nonhoarding OCD symptoms did not (J Atten Disord. 2016 Jul;20[7]:617-26).

In an earlier report by other investigators on 109 children seeking treatment for an anxiety disorder, 22% of the study population proved to have elevated levels of hoarding symptoms. They scored significantly higher than the nonhoarding group on measures of obsession-compulsion, anxiety, inattention, thought problems, rule breaking, aggression, social problems, major depression, and overall functional impairment. But of note, attention problems were a significantly stronger predictor of hoarding symptoms than were OCD or anxiety symptoms (J Anxiety Disord. 2015 Dec;36:9-14).

Discussant Eric Storch, PhD, said that it’s important for clinicians and parents to start taking child hoarding seriously as a legitimate treatment target.

“We know that if you start treatment early, you’re more likely to be successful versus when you start at age 57 and the clutter is 9 or 10 on a scale of 10,” said Dr. Storch, professor of pediatrics and director of clinical research for developmental pediatrics at the University of South Florida, Tampa.

Dr. Park reported having no financial conflicts of interest regarding her presentation.

[email protected]

SAN FRANCISCO – Most of the pediatric hoarding literature focuses on hoarding accompanied by obsessive-compulsive disorder. But, “I want to highlight that [attention-deficit/hyperactivity disorder] is across the board something that seems to come up in child hoarding behaviors quite a bit, mirroring the adult literature, which is that hoarding behavior may be much more strongly associated with ADHD than it is with OCD,” Jennifer M. Park, PhD, said at the annual conference of the Anxiety and Depression Association of America.

Multiple studies have established that the prevalence of child hoarding is 2%-3.7%. Onset is typically at age 11-15 years. The course is chronic, and it’s a condition that typically exacerbates over time.

“A lot of the adult literature has shown that hoarding behavior actually starts in childhood. In many retrospective reports, adults say, ‘I’ve had these problems ever since I was a kid,’ ” according to Dr. Park, a psychologist affiliated with Stanford (Calif.) University.

Yet childhood hoarding is not widely perceived as problematic. Indeed, many parents and clinicians view it as developmentally appropriate. That’s to a great extent because the presentation of child hoarding behavior often is very different from and less disturbing than adult hoarding for the obvious reason that parents can limit the amount of clutter in the home.

“I have a bunch of kids who have quite significant hoarding behavior, but the parents are really on top of making sure all of that is left in the closet or within the child’s playroom, or maybe a certain section of the house,” Dr. Park said. “They’re able to keep it contained.”

Also, children and young adolescents lack the resources to accumulate massive clutter. They can’t drive, and have little or no money, so they can’t go on compulsive shopping sprees. “What I have seen in the kids that I work with is they make up for that by collecting things like paper and sticks, rocks, wrappers – anything that might be free, or knickknacks they can pick up along the way,” she said.

The cognitive-behavioral model of hoarding was first described 2 decades ago. It names three main factors as key to maintaining hoarding behaviors: emotional attachment and beliefs associated with one’s possessions, often including anthropomorphization; avoidance behaviors due to severe distress at the prospect of discarding stuff; and information-processing deficits.

“The idea here is that deficits in executive function – things like planning, organization, and inhibition – these are known in an extensive literature to be really strongly associated with ADHD, and executive function deficits link well with hoarding disorder as well,” Dr. Park continued.

Dr. Park was the first author of a recent multicenter study of 431 youths aged 6-17 diagnosed with OCD. They were participants in the OCD Collaborative Genetics Study and the OCD Collaborative Genetics Association Study, during which they completed the Behavior Rating Inventory of Executive Functioning (BRIEF) and the Hoarding Rating Scale–Interview. Clinically significant levels of hoarding compulsions were identified in 113 subjects. Compared with the group with OCD but not hoarding, the OCD/hoarding group had significantly lower scores – meaning problematic deficits – on nearly all of the executive function subscales on the BRIEF, including working memory, emotional control, and planning/organization.

The two groups did not differ significantly in the prevalence of full DSM-IV ADHD. But the hoarding group had significantly more inattention and hyperactivity symptoms, and in a multivariate analysis adjusted for age, sex, and ADHD symptoms, deficits in executive function as measured on the BRIEF instrument were the strongest predictor of hoarding severity in the study population (J Psychiatr Res. 2016 Nov;82:141-8).

In another study by Dr. Park and her coinvestigators involving 99 youth diagnosed with ADHD, the severity of inattention and hyperactivity/impulsivity predicted clinically significant hoarding, whereas nonhoarding OCD symptoms did not (J Atten Disord. 2016 Jul;20[7]:617-26).

In an earlier report by other investigators on 109 children seeking treatment for an anxiety disorder, 22% of the study population proved to have elevated levels of hoarding symptoms. They scored significantly higher than the nonhoarding group on measures of obsession-compulsion, anxiety, inattention, thought problems, rule breaking, aggression, social problems, major depression, and overall functional impairment. But of note, attention problems were a significantly stronger predictor of hoarding symptoms than were OCD or anxiety symptoms (J Anxiety Disord. 2015 Dec;36:9-14).

Discussant Eric Storch, PhD, said that it’s important for clinicians and parents to start taking child hoarding seriously as a legitimate treatment target.

“We know that if you start treatment early, you’re more likely to be successful versus when you start at age 57 and the clutter is 9 or 10 on a scale of 10,” said Dr. Storch, professor of pediatrics and director of clinical research for developmental pediatrics at the University of South Florida, Tampa.

Dr. Park reported having no financial conflicts of interest regarding her presentation.

[email protected]

SAN FRANCISCO – Most of the pediatric hoarding literature focuses on hoarding accompanied by obsessive-compulsive disorder. But, “I want to highlight that [attention-deficit/hyperactivity disorder] is across the board something that seems to come up in child hoarding behaviors quite a bit, mirroring the adult literature, which is that hoarding behavior may be much more strongly associated with ADHD than it is with OCD,” Jennifer M. Park, PhD, said at the annual conference of the Anxiety and Depression Association of America.

Multiple studies have established that the prevalence of child hoarding is 2%-3.7%. Onset is typically at age 11-15 years. The course is chronic, and it’s a condition that typically exacerbates over time.

“A lot of the adult literature has shown that hoarding behavior actually starts in childhood. In many retrospective reports, adults say, ‘I’ve had these problems ever since I was a kid,’ ” according to Dr. Park, a psychologist affiliated with Stanford (Calif.) University.

Yet childhood hoarding is not widely perceived as problematic. Indeed, many parents and clinicians view it as developmentally appropriate. That’s to a great extent because the presentation of child hoarding behavior often is very different from and less disturbing than adult hoarding for the obvious reason that parents can limit the amount of clutter in the home.

“I have a bunch of kids who have quite significant hoarding behavior, but the parents are really on top of making sure all of that is left in the closet or within the child’s playroom, or maybe a certain section of the house,” Dr. Park said. “They’re able to keep it contained.”

Also, children and young adolescents lack the resources to accumulate massive clutter. They can’t drive, and have little or no money, so they can’t go on compulsive shopping sprees. “What I have seen in the kids that I work with is they make up for that by collecting things like paper and sticks, rocks, wrappers – anything that might be free, or knickknacks they can pick up along the way,” she said.

The cognitive-behavioral model of hoarding was first described 2 decades ago. It names three main factors as key to maintaining hoarding behaviors: emotional attachment and beliefs associated with one’s possessions, often including anthropomorphization; avoidance behaviors due to severe distress at the prospect of discarding stuff; and information-processing deficits.

“The idea here is that deficits in executive function – things like planning, organization, and inhibition – these are known in an extensive literature to be really strongly associated with ADHD, and executive function deficits link well with hoarding disorder as well,” Dr. Park continued.

Dr. Park was the first author of a recent multicenter study of 431 youths aged 6-17 diagnosed with OCD. They were participants in the OCD Collaborative Genetics Study and the OCD Collaborative Genetics Association Study, during which they completed the Behavior Rating Inventory of Executive Functioning (BRIEF) and the Hoarding Rating Scale–Interview. Clinically significant levels of hoarding compulsions were identified in 113 subjects. Compared with the group with OCD but not hoarding, the OCD/hoarding group had significantly lower scores – meaning problematic deficits – on nearly all of the executive function subscales on the BRIEF, including working memory, emotional control, and planning/organization.

The two groups did not differ significantly in the prevalence of full DSM-IV ADHD. But the hoarding group had significantly more inattention and hyperactivity symptoms, and in a multivariate analysis adjusted for age, sex, and ADHD symptoms, deficits in executive function as measured on the BRIEF instrument were the strongest predictor of hoarding severity in the study population (J Psychiatr Res. 2016 Nov;82:141-8).

In another study by Dr. Park and her coinvestigators involving 99 youth diagnosed with ADHD, the severity of inattention and hyperactivity/impulsivity predicted clinically significant hoarding, whereas nonhoarding OCD symptoms did not (J Atten Disord. 2016 Jul;20[7]:617-26).

In an earlier report by other investigators on 109 children seeking treatment for an anxiety disorder, 22% of the study population proved to have elevated levels of hoarding symptoms. They scored significantly higher than the nonhoarding group on measures of obsession-compulsion, anxiety, inattention, thought problems, rule breaking, aggression, social problems, major depression, and overall functional impairment. But of note, attention problems were a significantly stronger predictor of hoarding symptoms than were OCD or anxiety symptoms (J Anxiety Disord. 2015 Dec;36:9-14).

Discussant Eric Storch, PhD, said that it’s important for clinicians and parents to start taking child hoarding seriously as a legitimate treatment target.

“We know that if you start treatment early, you’re more likely to be successful versus when you start at age 57 and the clutter is 9 or 10 on a scale of 10,” said Dr. Storch, professor of pediatrics and director of clinical research for developmental pediatrics at the University of South Florida, Tampa.

Dr. Park reported having no financial conflicts of interest regarding her presentation.

[email protected]

Sunitinib, a multityrosine kinase inhibitor approved in 2006, has been shown to significantly prolong progression-free survival and overall survival in patients with metastatic renal cell cancer (mRCC). But while some patients with metastasized RCC have reportedly achieved complete remission with sunitinib, clinical and pathologic remission has seldom been described in reports, say researchers from Jinan University in China. They discuss a patient whose colonic metastasis of RCC resolved with microwave ablation and sunitinib.

Related: Incident Chronic Kidney Disease Following Kidney Cancer Surgery

The patient, who was diagnosed with right RCC, underwent a right radical nephrectomy. A pathologic report indicated clear-cell carcinoma of the kidney. Three years later, the patient presented with recurrent upper abdominal pain. An ultrasound scan revealed cholecystitis and gall bladder stones, and she was referred for treatment to the researchers’ hospital. During exploratory laparotomy, surgeons found a hepatic flexure colonic mass “firmly adhering” to the surrounding tissue; the mass perforated the intestine and could not be radically resected. The surgeons performed an ileostomy. The patient was started on sunitinib at 50 mg/d, on a schedule of 4 weeks of therapy followed by 2 weeks off therapy. During a follow-up, they found that the cancer had spread to the liver.  Metastasectomy was not possible, so the patient’s doctors chose microwave ablation. The researchers noted that there is currently little experience with microwave ablation in treatment of liver metastasis of RCC.

A follow-up computerized tomography (CT) scan showed that the treatment was shrinking the mass in the colon. Positron emission tomography-CT imaging showed no local signs of relapse. Three years after the microwave ablation, the patient underwent ileostomy reversal, hysterectomy, right hemicolectomy, and partial ileostomy; all pathologic results were benign.

Related: Major Cancer Death Rates Are Down

In about 25% of patients, RCC metastasizes postoperatively—usually to the lungs and liver, the researchers say. Colonic metastases are rare. On the basis of the patient’s clinical features, imaging data, and pathology results, the researchers concluded that sunitinib, with microwave ablation, can prevent unresectable hepatic metastases of RCC from evolving, and sunitinib alone can achieve clinical and pathologic remission of colonic metastases of RCC.

Source:
Peng B, Gong J. Urol Case Rep. 2017;12:78-80.
doi: 10.1016/j.eucr.2016.11.024.

Sunitinib, a multityrosine kinase inhibitor approved in 2006, has been shown to significantly prolong progression-free survival and overall survival in patients with metastatic renal cell cancer (mRCC). But while some patients with metastasized RCC have reportedly achieved complete remission with sunitinib, clinical and pathologic remission has seldom been described in reports, say researchers from Jinan University in China. They discuss a patient whose colonic metastasis of RCC resolved with microwave ablation and sunitinib.

Related: Incident Chronic Kidney Disease Following Kidney Cancer Surgery

The patient, who was diagnosed with right RCC, underwent a right radical nephrectomy. A pathologic report indicated clear-cell carcinoma of the kidney. Three years later, the patient presented with recurrent upper abdominal pain. An ultrasound scan revealed cholecystitis and gall bladder stones, and she was referred for treatment to the researchers’ hospital. During exploratory laparotomy, surgeons found a hepatic flexure colonic mass “firmly adhering” to the surrounding tissue; the mass perforated the intestine and could not be radically resected. The surgeons performed an ileostomy. The patient was started on sunitinib at 50 mg/d, on a schedule of 4 weeks of therapy followed by 2 weeks off therapy. During a follow-up, they found that the cancer had spread to the liver.  Metastasectomy was not possible, so the patient’s doctors chose microwave ablation. The researchers noted that there is currently little experience with microwave ablation in treatment of liver metastasis of RCC.

A follow-up computerized tomography (CT) scan showed that the treatment was shrinking the mass in the colon. Positron emission tomography-CT imaging showed no local signs of relapse. Three years after the microwave ablation, the patient underwent ileostomy reversal, hysterectomy, right hemicolectomy, and partial ileostomy; all pathologic results were benign.

Related: Major Cancer Death Rates Are Down

In about 25% of patients, RCC metastasizes postoperatively—usually to the lungs and liver, the researchers say. Colonic metastases are rare. On the basis of the patient’s clinical features, imaging data, and pathology results, the researchers concluded that sunitinib, with microwave ablation, can prevent unresectable hepatic metastases of RCC from evolving, and sunitinib alone can achieve clinical and pathologic remission of colonic metastases of RCC.

Source:
Peng B, Gong J. Urol Case Rep. 2017;12:78-80.
doi: 10.1016/j.eucr.2016.11.024.

Sunitinib, a multityrosine kinase inhibitor approved in 2006, has been shown to significantly prolong progression-free survival and overall survival in patients with metastatic renal cell cancer (mRCC). But while some patients with metastasized RCC have reportedly achieved complete remission with sunitinib, clinical and pathologic remission has seldom been described in reports, say researchers from Jinan University in China. They discuss a patient whose colonic metastasis of RCC resolved with microwave ablation and sunitinib.

Related: Incident Chronic Kidney Disease Following Kidney Cancer Surgery

The patient, who was diagnosed with right RCC, underwent a right radical nephrectomy. A pathologic report indicated clear-cell carcinoma of the kidney. Three years later, the patient presented with recurrent upper abdominal pain. An ultrasound scan revealed cholecystitis and gall bladder stones, and she was referred for treatment to the researchers’ hospital. During exploratory laparotomy, surgeons found a hepatic flexure colonic mass “firmly adhering” to the surrounding tissue; the mass perforated the intestine and could not be radically resected. The surgeons performed an ileostomy. The patient was started on sunitinib at 50 mg/d, on a schedule of 4 weeks of therapy followed by 2 weeks off therapy. During a follow-up, they found that the cancer had spread to the liver.  Metastasectomy was not possible, so the patient’s doctors chose microwave ablation. The researchers noted that there is currently little experience with microwave ablation in treatment of liver metastasis of RCC.

A follow-up computerized tomography (CT) scan showed that the treatment was shrinking the mass in the colon. Positron emission tomography-CT imaging showed no local signs of relapse. Three years after the microwave ablation, the patient underwent ileostomy reversal, hysterectomy, right hemicolectomy, and partial ileostomy; all pathologic results were benign.

Related: Major Cancer Death Rates Are Down

In about 25% of patients, RCC metastasizes postoperatively—usually to the lungs and liver, the researchers say. Colonic metastases are rare. On the basis of the patient’s clinical features, imaging data, and pathology results, the researchers concluded that sunitinib, with microwave ablation, can prevent unresectable hepatic metastases of RCC from evolving, and sunitinib alone can achieve clinical and pathologic remission of colonic metastases of RCC.

Source:
Peng B, Gong J. Urol Case Rep. 2017;12:78-80.
doi: 10.1016/j.eucr.2016.11.024.

A head-to-head comparison of 2 widely used drugs for macular edema due to central retinal vein occlusion—bevacizumab (Avastin) and aflibercept (Eylea)—found that both improved visual acuity (VA) similarly. But Eylea does it for $1,850 per dose, versus $60 per dose for Avastin.

In the Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2), National Eye Institute (NEI) researchers randomly assigned 362 patients to either Eylea or Avastin by eye injection every 4 weeks for 6 months. At 6 months, the researchers assessed VA, retinal thickness, and side effects.

On average, VA improved about 4 lines on an eye chart, from 20/100 to 20/40, more than doubling the ability to resolve fine detail, said Frederick Ferris, MD, director of the Division of Epidemiology and Clinical Applications at NEI. “For some patients it restores their ability to drive.”

Both drugs prevent the release of vascular endothelial growth factor, which causes swelling. The researchers found that macular edema declined significantly in both groups. The rates of adverse events, such as elevated intraocular pressure, were low and similar in both groups.

Retinal vein occlusion is associated with diabetes mellitus and hypertension. It is the second most common retinal vascular disease after diabetic retinopathy, according to NIH, and affects more than 16 million adults worldwide.

A head-to-head comparison of 2 widely used drugs for macular edema due to central retinal vein occlusion—bevacizumab (Avastin) and aflibercept (Eylea)—found that both improved visual acuity (VA) similarly. But Eylea does it for $1,850 per dose, versus $60 per dose for Avastin.

In the Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2), National Eye Institute (NEI) researchers randomly assigned 362 patients to either Eylea or Avastin by eye injection every 4 weeks for 6 months. At 6 months, the researchers assessed VA, retinal thickness, and side effects.

On average, VA improved about 4 lines on an eye chart, from 20/100 to 20/40, more than doubling the ability to resolve fine detail, said Frederick Ferris, MD, director of the Division of Epidemiology and Clinical Applications at NEI. “For some patients it restores their ability to drive.”

Both drugs prevent the release of vascular endothelial growth factor, which causes swelling. The researchers found that macular edema declined significantly in both groups. The rates of adverse events, such as elevated intraocular pressure, were low and similar in both groups.

Retinal vein occlusion is associated with diabetes mellitus and hypertension. It is the second most common retinal vascular disease after diabetic retinopathy, according to NIH, and affects more than 16 million adults worldwide.

A head-to-head comparison of 2 widely used drugs for macular edema due to central retinal vein occlusion—bevacizumab (Avastin) and aflibercept (Eylea)—found that both improved visual acuity (VA) similarly. But Eylea does it for $1,850 per dose, versus $60 per dose for Avastin.

In the Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2), National Eye Institute (NEI) researchers randomly assigned 362 patients to either Eylea or Avastin by eye injection every 4 weeks for 6 months. At 6 months, the researchers assessed VA, retinal thickness, and side effects.

On average, VA improved about 4 lines on an eye chart, from 20/100 to 20/40, more than doubling the ability to resolve fine detail, said Frederick Ferris, MD, director of the Division of Epidemiology and Clinical Applications at NEI. “For some patients it restores their ability to drive.”

Both drugs prevent the release of vascular endothelial growth factor, which causes swelling. The researchers found that macular edema declined significantly in both groups. The rates of adverse events, such as elevated intraocular pressure, were low and similar in both groups.

Retinal vein occlusion is associated with diabetes mellitus and hypertension. It is the second most common retinal vascular disease after diabetic retinopathy, according to NIH, and affects more than 16 million adults worldwide.

Image by Andre E.X. Brown

Patients with atrial fibrillation (AF) and renal impairment require dose reductions of non-vitamin K antagonist oral anticoagulants (NOACs).

But researchers found that 43% of these patients were potentially overdosed, and as many as 1 in 6 (13%) without renal impairment are potentially under dosed.

Failing to reduce the dose for patients with kidney disease increases their risk of bleeding, while under dosing patients without kidney disease puts them at greater risk of stroke. These inappropriate prescribing patterns may impact patient safety without providing benefit in effectiveness.

Using a large US database of de-identified, linked clinical and administrative claims information, the research team found 14,865 patients with AF who were prescribed apixaban, dabigatran, or rivaroxaban between October 1, 2020, and September 30, 2015. Of these, 1,473 had renal impairment.

All three drugs have a standard dose for most patients and a lower dose for patients with kidney issues. And their analysis revealed that 16% percent of all patients received a dose inconsistent with US Food and Drug Administration labeling.

The research team published its findings in the Journal of the American College of Cardiology.

“We conducted this study to highlight the prevalence of inappropriate dosing in routine clinical practice and the associated adverse outcomes,” said Peter Noseworthy, MD, of the Mayo Clinic in Rochester, Minnesota, and senior author of the paper.

“This study underscores the importance for physicians to be vigilant of kidney function when selecting or adjusting dose.”

Dr Noseworthy explained that overdosing is a fairly straightforward problem that can be avoided by regularly monitoring kidney function.

In the kidney-impaired patients who were potentially overdosed, the hazard ratio for the risk of major bleeding was 2.19 (95% confidence interval: 1.07 to 4.46). There was no statistically significant difference in stroke with the 3 NOACs pooled.

However, under dosing is more complex because a balance needs to be established between stroke reduction and bleeding risk, Dr Noseworthy pointed out.

Among the 13,392 patients without renal impairment and no indication for dose reduction, the hazard ratio for a higher risk of stroke was 4.87 (95% confidence interval: 1.30 to 18.26). There was no statistically significant difference in major bleeding in apixaban-treated patients nor statistically significant relationships in dabigatran- or rivaroxaban-treated patients without renal impairment.

“I think physicians often choose to reduce the dose,” Dr Noseworthy explained, “when they anticipate their patients are at a particularly high bleeding risk—independent of kidney function.”

“Dosing errors of these blood-thinning medications in patients with atrial fibrillation are common and have concerning adverse outcomes,” said Xiaoxi Yao, PhD, also of the Mayo Clinic in Rochester, Minnesota, and lead author of the paper.

Dr Yao noted that the number of patients using these drugs has increased since their introduction in 2010. Before that, the standard blood-thinning drug was warfarin, which requires constant monitoring and doctor visits.

Image by Andre E.X. Brown

Patients with atrial fibrillation (AF) and renal impairment require dose reductions of non-vitamin K antagonist oral anticoagulants (NOACs).

But researchers found that 43% of these patients were potentially overdosed, and as many as 1 in 6 (13%) without renal impairment are potentially under dosed.

Failing to reduce the dose for patients with kidney disease increases their risk of bleeding, while under dosing patients without kidney disease puts them at greater risk of stroke. These inappropriate prescribing patterns may impact patient safety without providing benefit in effectiveness.

Using a large US database of de-identified, linked clinical and administrative claims information, the research team found 14,865 patients with AF who were prescribed apixaban, dabigatran, or rivaroxaban between October 1, 2020, and September 30, 2015. Of these, 1,473 had renal impairment.

All three drugs have a standard dose for most patients and a lower dose for patients with kidney issues. And their analysis revealed that 16% percent of all patients received a dose inconsistent with US Food and Drug Administration labeling.

The research team published its findings in the Journal of the American College of Cardiology.

“We conducted this study to highlight the prevalence of inappropriate dosing in routine clinical practice and the associated adverse outcomes,” said Peter Noseworthy, MD, of the Mayo Clinic in Rochester, Minnesota, and senior author of the paper.

“This study underscores the importance for physicians to be vigilant of kidney function when selecting or adjusting dose.”

Dr Noseworthy explained that overdosing is a fairly straightforward problem that can be avoided by regularly monitoring kidney function.

In the kidney-impaired patients who were potentially overdosed, the hazard ratio for the risk of major bleeding was 2.19 (95% confidence interval: 1.07 to 4.46). There was no statistically significant difference in stroke with the 3 NOACs pooled.

However, under dosing is more complex because a balance needs to be established between stroke reduction and bleeding risk, Dr Noseworthy pointed out.

Among the 13,392 patients without renal impairment and no indication for dose reduction, the hazard ratio for a higher risk of stroke was 4.87 (95% confidence interval: 1.30 to 18.26). There was no statistically significant difference in major bleeding in apixaban-treated patients nor statistically significant relationships in dabigatran- or rivaroxaban-treated patients without renal impairment.

“I think physicians often choose to reduce the dose,” Dr Noseworthy explained, “when they anticipate their patients are at a particularly high bleeding risk—independent of kidney function.”

“Dosing errors of these blood-thinning medications in patients with atrial fibrillation are common and have concerning adverse outcomes,” said Xiaoxi Yao, PhD, also of the Mayo Clinic in Rochester, Minnesota, and lead author of the paper.

Dr Yao noted that the number of patients using these drugs has increased since their introduction in 2010. Before that, the standard blood-thinning drug was warfarin, which requires constant monitoring and doctor visits.

Image by Andre E.X. Brown

Patients with atrial fibrillation (AF) and renal impairment require dose reductions of non-vitamin K antagonist oral anticoagulants (NOACs).

But researchers found that 43% of these patients were potentially overdosed, and as many as 1 in 6 (13%) without renal impairment are potentially under dosed.

Failing to reduce the dose for patients with kidney disease increases their risk of bleeding, while under dosing patients without kidney disease puts them at greater risk of stroke. These inappropriate prescribing patterns may impact patient safety without providing benefit in effectiveness.

Using a large US database of de-identified, linked clinical and administrative claims information, the research team found 14,865 patients with AF who were prescribed apixaban, dabigatran, or rivaroxaban between October 1, 2020, and September 30, 2015. Of these, 1,473 had renal impairment.

All three drugs have a standard dose for most patients and a lower dose for patients with kidney issues. And their analysis revealed that 16% percent of all patients received a dose inconsistent with US Food and Drug Administration labeling.

The research team published its findings in the Journal of the American College of Cardiology.

“We conducted this study to highlight the prevalence of inappropriate dosing in routine clinical practice and the associated adverse outcomes,” said Peter Noseworthy, MD, of the Mayo Clinic in Rochester, Minnesota, and senior author of the paper.

“This study underscores the importance for physicians to be vigilant of kidney function when selecting or adjusting dose.”

Dr Noseworthy explained that overdosing is a fairly straightforward problem that can be avoided by regularly monitoring kidney function.

In the kidney-impaired patients who were potentially overdosed, the hazard ratio for the risk of major bleeding was 2.19 (95% confidence interval: 1.07 to 4.46). There was no statistically significant difference in stroke with the 3 NOACs pooled.

However, under dosing is more complex because a balance needs to be established between stroke reduction and bleeding risk, Dr Noseworthy pointed out.

Among the 13,392 patients without renal impairment and no indication for dose reduction, the hazard ratio for a higher risk of stroke was 4.87 (95% confidence interval: 1.30 to 18.26). There was no statistically significant difference in major bleeding in apixaban-treated patients nor statistically significant relationships in dabigatran- or rivaroxaban-treated patients without renal impairment.

“I think physicians often choose to reduce the dose,” Dr Noseworthy explained, “when they anticipate their patients are at a particularly high bleeding risk—independent of kidney function.”

“Dosing errors of these blood-thinning medications in patients with atrial fibrillation are common and have concerning adverse outcomes,” said Xiaoxi Yao, PhD, also of the Mayo Clinic in Rochester, Minnesota, and lead author of the paper.

Dr Yao noted that the number of patients using these drugs has increased since their introduction in 2010. Before that, the standard blood-thinning drug was warfarin, which requires constant monitoring and doctor visits.

Photo © ASCO/Danny Morton 2017

CHICAGO—Three of 6 pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL) whose CD19 chimeric antigen receptor (CAR) T cells did not persist even after reinfusion demonstrated persistence when the PD-1 checkpoint inhibitor pembrolizumab was added to the regimen.

CAR T cells can persist for months or even years and have the potential to mediate long-term disease control.

But some patients recover their normal B cells, which is a marker of loss of functional CAR T cells. These patients are at a higher risk of disease relapse.

Investigators, therefore, undertook a pilot study to determine whether PD-1 checkpoint pathway inhibition can improve CAR T persistence in these patients.

Shannon L. Maude, MD, of the Children’s Hospital of Philadelphia and the University of Pennsylvania Perelman School of Medicine, shared some of the patient cases in this pilot study at the ASCO 2017 Annual Meeting (Abstract 103*).

The investigators hypothesized that possible anti-murine immunogenicity could be causing poor CAR T-cell persistence, since the first CAR T developed used scFv domains of murine origin.

If T-cell exhaustion caused poor CAR T-cell persistence, immune checkpoints might play a role. In this case, combination with PD-1 checkpoint blockade could improve persistence, they hypothesized.

The investigators proposed to administer a repeat CAR T-cell infusion for relapsed or refractory ALL patients with poor persistence and add pembrolizumab after retreatment if the patients still had poor persistence. Patients were offered the option of another reinfusion prior to treatment with pembrolizumab if their CAR T-cell persistence continued to be poor.

Investigators added pembrolizumab no earlier than 14 days after infusion and only after patients recovered from cytokine release syndrome (CRS).

The infusions in the pilot study were humanized CART19 (huCART19, CTL119), unless otherwise specified.

Patient 1 – Pembrolizumab for partial response

This patient had no response to the prior murine CD19 CAR infusion, but responded well to infusion with huCART19 with good CAR T-cell proliferation.

By day 28, the patient had achieved a complete response (CR) in bone marrow but had a minimal residual disease (MRD) level of 1.2%.

At 7 weeks, the patient had a CD19+ relapse with low levels of huCART19.

Investigators added pembrolizumb on day 52 after infusion, and the patient had a modest increase in huCART19.

The patient had a temporary clearance of peripheral blasts followed by disease progression.

Patient 2 – Pembrolizumab for no response

This patient had a CD19+ relapse at 12 months after prior murine CD19 CAR infusion.

The patient was treated with huCART19, had good proliferation, but a rapid drop of CART19, and no response of the disease with a CD19+ relapse.

The patient had a reinfusion of huCART19 at 6 weeks and investigators added pembrolizumab on day 14 after reinfusion.

The patient experienced good huCART19 proliferation and prolonged persistence, but by day 28 had persistent disease, this time with decreased expression of CD19+ cells.

Patient 3 – Pembrolizumab for poor persistence

 This patient had a CR with a prior murine CD19 CAR, but had poor persistence and early B cell recovery at 2 months.

The patient had a CD19+ relapse, was treated with huCART19, and had good proliferation again.

The patient achieved an MRD-negative CR, but because of short persistence and early B-cell recovery at 2 months, relapsed at 15 months.

The patient was reinfused at 17 months and pembrolizumab was added on day 14. The patient entered CR with prolonged persistence, but ultimately B-cell recovery occurred.

The patient was reinfused a third time, and pembrolizumab was added to the regimen every 3 weeks. The patient is experiencing prolonged persistence and continued B-cell aplasia.

Patient 4 – Pembrolizumab for poor persistence

This patient had achieved a CR with murine CAR19, but had a CD19+ relapse at 9 months. The patient then received huCART19, had good proliferation and achieved a CR, but had short persistence and B-cell recovery at 2 months.

The patient relapsed at 12 months and was reinfused with huCART19 at 14 months.

Pembrolizumab was added on day 14 after reinfusion, but the patient had no huCART19 proliferation, no response, and CD19+ MRD.

Patient 5 – Pembrolizumab for poor persistence

The patient responded to a prior murine CART19, but had a CD19+ relapse at 12 months.

The patient was infused with huCART19 and had good proliferation but short persistence. The patient was reinfused at 6 months, but again had short persistence.

The patient was reinfused again at 8 months because of B-cell recovery, and pembrolizumab was added on day 14 and administered every 3 weeks thereafter.

The patient is experiencing prolonged persistence and continued B-cell aplasia.

Patient 6 – Pembrolizumab for lymphomatous disease

This patient, who had widespread lymphadenopathy and M3 bone marrow, had not received prior CAR T cells and was treated for the first time with a murine CART19 for r/r ALL.

The patient had good expansion of CART19, but by day 28, PET scan showed widespread lymph node disease despite CR in the bone marrow.

The patient was given pembrolizumab on day 32 after infusion and every 2-3 weeks thereafter. After the addition of pembrolizumab, the patient had increased CART19 cells in blood and a significant decrease in PET-avid disease.

Summary

Three of six patients achieved objective clinical responses with pembrolizumab: 2 had prolonged B-cell aplasia, and another had a decrease in PET-avid lymphomatous disease.

The addition of pembrolizumab was also well tolerated by the patients, with minimal side effects of fever in 2 patients, cytopenias in 2 patients, and no instances of severe CRS.

The investigators believe the addition of checkpoint pathway inhibitors has the potential to prolong CAR T-cell persistence and warrants further investigation.

Photo © ASCO/Danny Morton 2017

CHICAGO—Three of 6 pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL) whose CD19 chimeric antigen receptor (CAR) T cells did not persist even after reinfusion demonstrated persistence when the PD-1 checkpoint inhibitor pembrolizumab was added to the regimen.

CAR T cells can persist for months or even years and have the potential to mediate long-term disease control.

But some patients recover their normal B cells, which is a marker of loss of functional CAR T cells. These patients are at a higher risk of disease relapse.

Investigators, therefore, undertook a pilot study to determine whether PD-1 checkpoint pathway inhibition can improve CAR T persistence in these patients.

Shannon L. Maude, MD, of the Children’s Hospital of Philadelphia and the University of Pennsylvania Perelman School of Medicine, shared some of the patient cases in this pilot study at the ASCO 2017 Annual Meeting (Abstract 103*).

The investigators hypothesized that possible anti-murine immunogenicity could be causing poor CAR T-cell persistence, since the first CAR T developed used scFv domains of murine origin.

If T-cell exhaustion caused poor CAR T-cell persistence, immune checkpoints might play a role. In this case, combination with PD-1 checkpoint blockade could improve persistence, they hypothesized.

The investigators proposed to administer a repeat CAR T-cell infusion for relapsed or refractory ALL patients with poor persistence and add pembrolizumab after retreatment if the patients still had poor persistence. Patients were offered the option of another reinfusion prior to treatment with pembrolizumab if their CAR T-cell persistence continued to be poor.

Investigators added pembrolizumab no earlier than 14 days after infusion and only after patients recovered from cytokine release syndrome (CRS).

The infusions in the pilot study were humanized CART19 (huCART19, CTL119), unless otherwise specified.

Patient 1 – Pembrolizumab for partial response

This patient had no response to the prior murine CD19 CAR infusion, but responded well to infusion with huCART19 with good CAR T-cell proliferation.

By day 28, the patient had achieved a complete response (CR) in bone marrow but had a minimal residual disease (MRD) level of 1.2%.

At 7 weeks, the patient had a CD19+ relapse with low levels of huCART19.

Investigators added pembrolizumb on day 52 after infusion, and the patient had a modest increase in huCART19.

The patient had a temporary clearance of peripheral blasts followed by disease progression.

Patient 2 – Pembrolizumab for no response

This patient had a CD19+ relapse at 12 months after prior murine CD19 CAR infusion.

The patient was treated with huCART19, had good proliferation, but a rapid drop of CART19, and no response of the disease with a CD19+ relapse.

The patient had a reinfusion of huCART19 at 6 weeks and investigators added pembrolizumab on day 14 after reinfusion.

The patient experienced good huCART19 proliferation and prolonged persistence, but by day 28 had persistent disease, this time with decreased expression of CD19+ cells.

Patient 3 – Pembrolizumab for poor persistence

 This patient had a CR with a prior murine CD19 CAR, but had poor persistence and early B cell recovery at 2 months.

The patient had a CD19+ relapse, was treated with huCART19, and had good proliferation again.

The patient achieved an MRD-negative CR, but because of short persistence and early B-cell recovery at 2 months, relapsed at 15 months.

The patient was reinfused at 17 months and pembrolizumab was added on day 14. The patient entered CR with prolonged persistence, but ultimately B-cell recovery occurred.

The patient was reinfused a third time, and pembrolizumab was added to the regimen every 3 weeks. The patient is experiencing prolonged persistence and continued B-cell aplasia.

Patient 4 – Pembrolizumab for poor persistence

This patient had achieved a CR with murine CAR19, but had a CD19+ relapse at 9 months. The patient then received huCART19, had good proliferation and achieved a CR, but had short persistence and B-cell recovery at 2 months.

The patient relapsed at 12 months and was reinfused with huCART19 at 14 months.

Pembrolizumab was added on day 14 after reinfusion, but the patient had no huCART19 proliferation, no response, and CD19+ MRD.

Patient 5 – Pembrolizumab for poor persistence

The patient responded to a prior murine CART19, but had a CD19+ relapse at 12 months.

The patient was infused with huCART19 and had good proliferation but short persistence. The patient was reinfused at 6 months, but again had short persistence.

The patient was reinfused again at 8 months because of B-cell recovery, and pembrolizumab was added on day 14 and administered every 3 weeks thereafter.

The patient is experiencing prolonged persistence and continued B-cell aplasia.

Patient 6 – Pembrolizumab for lymphomatous disease

This patient, who had widespread lymphadenopathy and M3 bone marrow, had not received prior CAR T cells and was treated for the first time with a murine CART19 for r/r ALL.

The patient had good expansion of CART19, but by day 28, PET scan showed widespread lymph node disease despite CR in the bone marrow.

The patient was given pembrolizumab on day 32 after infusion and every 2-3 weeks thereafter. After the addition of pembrolizumab, the patient had increased CART19 cells in blood and a significant decrease in PET-avid disease.

Summary

Three of six patients achieved objective clinical responses with pembrolizumab: 2 had prolonged B-cell aplasia, and another had a decrease in PET-avid lymphomatous disease.

The addition of pembrolizumab was also well tolerated by the patients, with minimal side effects of fever in 2 patients, cytopenias in 2 patients, and no instances of severe CRS.

The investigators believe the addition of checkpoint pathway inhibitors has the potential to prolong CAR T-cell persistence and warrants further investigation.

Photo © ASCO/Danny Morton 2017

CHICAGO—Three of 6 pediatric patients with relapsed or refractory acute lymphoblastic leukemia (ALL) whose CD19 chimeric antigen receptor (CAR) T cells did not persist even after reinfusion demonstrated persistence when the PD-1 checkpoint inhibitor pembrolizumab was added to the regimen.

CAR T cells can persist for months or even years and have the potential to mediate long-term disease control.

But some patients recover their normal B cells, which is a marker of loss of functional CAR T cells. These patients are at a higher risk of disease relapse.

Investigators, therefore, undertook a pilot study to determine whether PD-1 checkpoint pathway inhibition can improve CAR T persistence in these patients.

Shannon L. Maude, MD, of the Children’s Hospital of Philadelphia and the University of Pennsylvania Perelman School of Medicine, shared some of the patient cases in this pilot study at the ASCO 2017 Annual Meeting (Abstract 103*).

The investigators hypothesized that possible anti-murine immunogenicity could be causing poor CAR T-cell persistence, since the first CAR T developed used scFv domains of murine origin.

If T-cell exhaustion caused poor CAR T-cell persistence, immune checkpoints might play a role. In this case, combination with PD-1 checkpoint blockade could improve persistence, they hypothesized.

The investigators proposed to administer a repeat CAR T-cell infusion for relapsed or refractory ALL patients with poor persistence and add pembrolizumab after retreatment if the patients still had poor persistence. Patients were offered the option of another reinfusion prior to treatment with pembrolizumab if their CAR T-cell persistence continued to be poor.

Investigators added pembrolizumab no earlier than 14 days after infusion and only after patients recovered from cytokine release syndrome (CRS).

The infusions in the pilot study were humanized CART19 (huCART19, CTL119), unless otherwise specified.

Patient 1 – Pembrolizumab for partial response

This patient had no response to the prior murine CD19 CAR infusion, but responded well to infusion with huCART19 with good CAR T-cell proliferation.

By day 28, the patient had achieved a complete response (CR) in bone marrow but had a minimal residual disease (MRD) level of 1.2%.

At 7 weeks, the patient had a CD19+ relapse with low levels of huCART19.

Investigators added pembrolizumb on day 52 after infusion, and the patient had a modest increase in huCART19.

The patient had a temporary clearance of peripheral blasts followed by disease progression.

Patient 2 – Pembrolizumab for no response

This patient had a CD19+ relapse at 12 months after prior murine CD19 CAR infusion.

The patient was treated with huCART19, had good proliferation, but a rapid drop of CART19, and no response of the disease with a CD19+ relapse.

The patient had a reinfusion of huCART19 at 6 weeks and investigators added pembrolizumab on day 14 after reinfusion.

The patient experienced good huCART19 proliferation and prolonged persistence, but by day 28 had persistent disease, this time with decreased expression of CD19+ cells.

Patient 3 – Pembrolizumab for poor persistence

 This patient had a CR with a prior murine CD19 CAR, but had poor persistence and early B cell recovery at 2 months.

The patient had a CD19+ relapse, was treated with huCART19, and had good proliferation again.

The patient achieved an MRD-negative CR, but because of short persistence and early B-cell recovery at 2 months, relapsed at 15 months.

The patient was reinfused at 17 months and pembrolizumab was added on day 14. The patient entered CR with prolonged persistence, but ultimately B-cell recovery occurred.

The patient was reinfused a third time, and pembrolizumab was added to the regimen every 3 weeks. The patient is experiencing prolonged persistence and continued B-cell aplasia.

Patient 4 – Pembrolizumab for poor persistence

This patient had achieved a CR with murine CAR19, but had a CD19+ relapse at 9 months. The patient then received huCART19, had good proliferation and achieved a CR, but had short persistence and B-cell recovery at 2 months.

The patient relapsed at 12 months and was reinfused with huCART19 at 14 months.

Pembrolizumab was added on day 14 after reinfusion, but the patient had no huCART19 proliferation, no response, and CD19+ MRD.

Patient 5 – Pembrolizumab for poor persistence

The patient responded to a prior murine CART19, but had a CD19+ relapse at 12 months.

The patient was infused with huCART19 and had good proliferation but short persistence. The patient was reinfused at 6 months, but again had short persistence.

The patient was reinfused again at 8 months because of B-cell recovery, and pembrolizumab was added on day 14 and administered every 3 weeks thereafter.

The patient is experiencing prolonged persistence and continued B-cell aplasia.

Patient 6 – Pembrolizumab for lymphomatous disease

This patient, who had widespread lymphadenopathy and M3 bone marrow, had not received prior CAR T cells and was treated for the first time with a murine CART19 for r/r ALL.

The patient had good expansion of CART19, but by day 28, PET scan showed widespread lymph node disease despite CR in the bone marrow.

The patient was given pembrolizumab on day 32 after infusion and every 2-3 weeks thereafter. After the addition of pembrolizumab, the patient had increased CART19 cells in blood and a significant decrease in PET-avid disease.

Summary

Three of six patients achieved objective clinical responses with pembrolizumab: 2 had prolonged B-cell aplasia, and another had a decrease in PET-avid lymphomatous disease.

The addition of pembrolizumab was also well tolerated by the patients, with minimal side effects of fever in 2 patients, cytopenias in 2 patients, and no instances of severe CRS.

The investigators believe the addition of checkpoint pathway inhibitors has the potential to prolong CAR T-cell persistence and warrants further investigation.