CORONADO, CALIF. – The use of radioactive iodine in patients with papillary thyroid cancer showed a small but statistically significant survival benefit for all tumor size categories, a long-term analysis of national data suggested.

“The incidence of papillary thyroid carcinoma is rapidly rising, but the survival advantage of radioactive iodine ablation has not been confirmed,” Dr. Paritosh Suman said at the annual meeting of the American Thyroid Association.

©Sebastian Kaulitzki/Fotolia.com

To investigate the effect of radioactive iodine (RAI) on papillary thyroid cancer mortality, Dr. Suman and his associates identified 108,565 patients from the National Cancer Data Base who were diagnosed with papillary thyroid cancer and underwent total or near total thyroidectomy between 1998 and 2006.

The investigators classified tumors into one of four groups by diameter size: 10 mm or less, 11-20 mm, 21-40 mm, and greater than 40 mm. The study researchers used Cox regression analysis to quantify the effect of radioactive iodine, adjusting for clinicopathologic, demographic, and socioeconomic variables. A total of 52% of the patients were older than 45 years, 77% were female, and 54% received RAI.

Factors predicting the use of RAI were being male, having positive margins, having cervical lymph node involvement, and having a tumor size greater than 4 cm in diameter, said Dr. Suman, an endocrinology surgery fellow at North Shore University Health System in Evanston, Ill. The 10-year overall survival rate was 90% in those who received RAI, compared with 87.4% among those who did not, for a small but statistically significant survival advantage (P < .0001).

Among patients who received RAI, the 10-year survival advantage by diameter of tumor was 3.4% for those with tumors 10 mm or less; 2.8% with 11-20 mm; 3.3% with 21-40 mm, and 5.7% with greater than 40 mm.

Age also played a factor, with a 10-year survival advantage of 0.5% for those aged 18-35 years; 1.5% for those aged 36-45 years; 0.9% for those aged 46-55 years; 0.6% for those aged 56-65 years; and 2.1% for those older than 65 years. Both men and women who received RAI had a statistically significant survival advantage at 10 years (3.9% and 1.6%, respectively).

When the researchers assessed the 10-year survival advantage by lymph node category of patients who received RAI, the rates were 2.9% for N-0, 4.2% for N-1, 5.2% for N-1A, and 5.8% for N-1B. By margin status, the 10-year survival advantage was 3.1% for negative margins, 3.6% for positive margins, 3.5% for microscopic margins, and 8.8% for gross margins.

In an analysis of all patients with very low-risk, low-risk, and high-risk papillary thyroid carcinoma according to ATA guidelines for the use of RAI, the study authors found a 10-year survival advantage of RAI in each of the three categories.

Among patients with very low-risk papillary thyroid carcinoma, the rate of 10-year survival was 92.2% among those who received RAI, compared with 89% among those who did not (hazard ratio, 0.74). Similar associations were observed in those with low-risk carcinoma (91.8% vs. 89%; HR, 0.80) and in those with high-risk carcinoma (86.2% vs. 79.2%; HR, 0.71).

“RAI is associated with a statistically significant but small overall survival advantage for most patients,” Dr. Suman said. “High-risk patients, defined by large tumor size, lymph node involvement, and gross margins, achieve the greatest benefit with RAI ablation.”

Dr. Suman reported having no relevant financial disclosures.

[email protected]

On Twitter @dougbrunk

CORONADO, CALIF. – The use of radioactive iodine in patients with papillary thyroid cancer showed a small but statistically significant survival benefit for all tumor size categories, a long-term analysis of national data suggested.

“The incidence of papillary thyroid carcinoma is rapidly rising, but the survival advantage of radioactive iodine ablation has not been confirmed,” Dr. Paritosh Suman said at the annual meeting of the American Thyroid Association.

©Sebastian Kaulitzki/Fotolia.com

To investigate the effect of radioactive iodine (RAI) on papillary thyroid cancer mortality, Dr. Suman and his associates identified 108,565 patients from the National Cancer Data Base who were diagnosed with papillary thyroid cancer and underwent total or near total thyroidectomy between 1998 and 2006.

The investigators classified tumors into one of four groups by diameter size: 10 mm or less, 11-20 mm, 21-40 mm, and greater than 40 mm. The study researchers used Cox regression analysis to quantify the effect of radioactive iodine, adjusting for clinicopathologic, demographic, and socioeconomic variables. A total of 52% of the patients were older than 45 years, 77% were female, and 54% received RAI.

Factors predicting the use of RAI were being male, having positive margins, having cervical lymph node involvement, and having a tumor size greater than 4 cm in diameter, said Dr. Suman, an endocrinology surgery fellow at North Shore University Health System in Evanston, Ill. The 10-year overall survival rate was 90% in those who received RAI, compared with 87.4% among those who did not, for a small but statistically significant survival advantage (P < .0001).

Among patients who received RAI, the 10-year survival advantage by diameter of tumor was 3.4% for those with tumors 10 mm or less; 2.8% with 11-20 mm; 3.3% with 21-40 mm, and 5.7% with greater than 40 mm.

Age also played a factor, with a 10-year survival advantage of 0.5% for those aged 18-35 years; 1.5% for those aged 36-45 years; 0.9% for those aged 46-55 years; 0.6% for those aged 56-65 years; and 2.1% for those older than 65 years. Both men and women who received RAI had a statistically significant survival advantage at 10 years (3.9% and 1.6%, respectively).

When the researchers assessed the 10-year survival advantage by lymph node category of patients who received RAI, the rates were 2.9% for N-0, 4.2% for N-1, 5.2% for N-1A, and 5.8% for N-1B. By margin status, the 10-year survival advantage was 3.1% for negative margins, 3.6% for positive margins, 3.5% for microscopic margins, and 8.8% for gross margins.

In an analysis of all patients with very low-risk, low-risk, and high-risk papillary thyroid carcinoma according to ATA guidelines for the use of RAI, the study authors found a 10-year survival advantage of RAI in each of the three categories.

Among patients with very low-risk papillary thyroid carcinoma, the rate of 10-year survival was 92.2% among those who received RAI, compared with 89% among those who did not (hazard ratio, 0.74). Similar associations were observed in those with low-risk carcinoma (91.8% vs. 89%; HR, 0.80) and in those with high-risk carcinoma (86.2% vs. 79.2%; HR, 0.71).

“RAI is associated with a statistically significant but small overall survival advantage for most patients,” Dr. Suman said. “High-risk patients, defined by large tumor size, lymph node involvement, and gross margins, achieve the greatest benefit with RAI ablation.”

Dr. Suman reported having no relevant financial disclosures.

[email protected]

On Twitter @dougbrunk

CORONADO, CALIF. – The use of radioactive iodine in patients with papillary thyroid cancer showed a small but statistically significant survival benefit for all tumor size categories, a long-term analysis of national data suggested.

“The incidence of papillary thyroid carcinoma is rapidly rising, but the survival advantage of radioactive iodine ablation has not been confirmed,” Dr. Paritosh Suman said at the annual meeting of the American Thyroid Association.

©Sebastian Kaulitzki/Fotolia.com

To investigate the effect of radioactive iodine (RAI) on papillary thyroid cancer mortality, Dr. Suman and his associates identified 108,565 patients from the National Cancer Data Base who were diagnosed with papillary thyroid cancer and underwent total or near total thyroidectomy between 1998 and 2006.

The investigators classified tumors into one of four groups by diameter size: 10 mm or less, 11-20 mm, 21-40 mm, and greater than 40 mm. The study researchers used Cox regression analysis to quantify the effect of radioactive iodine, adjusting for clinicopathologic, demographic, and socioeconomic variables. A total of 52% of the patients were older than 45 years, 77% were female, and 54% received RAI.

Factors predicting the use of RAI were being male, having positive margins, having cervical lymph node involvement, and having a tumor size greater than 4 cm in diameter, said Dr. Suman, an endocrinology surgery fellow at North Shore University Health System in Evanston, Ill. The 10-year overall survival rate was 90% in those who received RAI, compared with 87.4% among those who did not, for a small but statistically significant survival advantage (P < .0001).

Among patients who received RAI, the 10-year survival advantage by diameter of tumor was 3.4% for those with tumors 10 mm or less; 2.8% with 11-20 mm; 3.3% with 21-40 mm, and 5.7% with greater than 40 mm.

Age also played a factor, with a 10-year survival advantage of 0.5% for those aged 18-35 years; 1.5% for those aged 36-45 years; 0.9% for those aged 46-55 years; 0.6% for those aged 56-65 years; and 2.1% for those older than 65 years. Both men and women who received RAI had a statistically significant survival advantage at 10 years (3.9% and 1.6%, respectively).

When the researchers assessed the 10-year survival advantage by lymph node category of patients who received RAI, the rates were 2.9% for N-0, 4.2% for N-1, 5.2% for N-1A, and 5.8% for N-1B. By margin status, the 10-year survival advantage was 3.1% for negative margins, 3.6% for positive margins, 3.5% for microscopic margins, and 8.8% for gross margins.

In an analysis of all patients with very low-risk, low-risk, and high-risk papillary thyroid carcinoma according to ATA guidelines for the use of RAI, the study authors found a 10-year survival advantage of RAI in each of the three categories.

Among patients with very low-risk papillary thyroid carcinoma, the rate of 10-year survival was 92.2% among those who received RAI, compared with 89% among those who did not (hazard ratio, 0.74). Similar associations were observed in those with low-risk carcinoma (91.8% vs. 89%; HR, 0.80) and in those with high-risk carcinoma (86.2% vs. 79.2%; HR, 0.71).

“RAI is associated with a statistically significant but small overall survival advantage for most patients,” Dr. Suman said. “High-risk patients, defined by large tumor size, lymph node involvement, and gross margins, achieve the greatest benefit with RAI ablation.”

Dr. Suman reported having no relevant financial disclosures.

[email protected]

On Twitter @dougbrunk

One serious problem with being an advocate of correctional mental health services is that you run the risk of coming across as an apologist, a Pollyanna, or a defender of the status quo. This is true even though every week I meet someone with an addiction problem so severe that he’d be unable to voluntarily seek or stay in treatment in the community. For someone like that, an arrest can be lifesaving. But to point this out will lead people to believe that I must oppose ready access to community care, pretrial diversion, alternative sentencing, mental health courts, or anything related to alternatives to incarceration.

That isn’t the case. Many problems require more than one solution. What I oppose is the idea that the solution has to be a simple dichotomous choice between arrest and incarceration versus community care. I’ve found discussions about criminalization of people with mental illnesses to be polarizing and unproductive. There will always be people with mental illnesses in jail and prison, because – like people with diabetes, heart disease, or AIDS – they sometimes commit very serious crimes. As a care provider, my view is that a patient’s need for treatment is independent of criminal culpability. An ill person deserves appropriate and skilled health care, regardless of the treatment setting. Moving someone from an understaffed, overcrowded correctional facility to an understaffed, overcrowded state hospital hardly solves the problem.

People make the argument that money spent on corrections would be better spent elsewhere, on services for at-risk youth, or on community substance abuse and mental health programs. I agree that all these programs are needed, but what rarely gets mentioned is that when money is diverted from jails and prisons, part of that money also includes funding for inmate health care. Taking away this money is like stealing a coat from a blind beggar in the winter time. If you want to make a serious problem worse, by all means, take away what little we have.

How much money are we talking here, anyway?

By some estimates, the money spent on health care for all American prisons is about $7.7 billion per year. That includes physician and related health care professional costs, laboratory and diagnostic testing, hospitalization costs, as well as medications. Fourteen percent of that, or about $1 billion, goes to mental health care. Those costs are expected to rise as the prison population continues to age. Meanwhile, federal spending on mandatory health care programs in 2013 was about $1 trillion. When the prison health care budget represents less than 1% of health care spending nationally, this doesn’t seem to be enough to be quibbling about and certainly not enough to be cutting or diverting elsewhere.

But of course, the correctional nihilists will respond, “You get what you pay for.” Inevitably, low-cost care becomes equivalent to low-quality care in the eyes of many Americans. But if you compare American medical outcomes globally, it’s been well established that we have fallen behind many countries in life expectancy and infant mortality, despite heavy investment in a broad spectrum of services and interventions.

Let’s compare that to prison. Because of data gathered through the 2000 Federal Death in Custody Reporting Act, as well as other studies, prisons have been able to demonstrate reduced mortality, compared with age-matched men in free society, particularly for minorities. That mortality rate doubles after release. Clearly, prisons appear to be keeping people alive more efficiently and at a fraction of the cost of our community services.

This is not to imply that incarceration should be the answer to every social problem. This is my response to the naysayers and nihilists who believe that jails and prisons are so far gone they are not worth investing in. The lives of many prisoners depend on that investment.

Dr. Hanson is a forensic psychiatrist and coauthor of Shrink Rap: Three Psychiatrists Explain Their Work. The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson’s employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

One serious problem with being an advocate of correctional mental health services is that you run the risk of coming across as an apologist, a Pollyanna, or a defender of the status quo. This is true even though every week I meet someone with an addiction problem so severe that he’d be unable to voluntarily seek or stay in treatment in the community. For someone like that, an arrest can be lifesaving. But to point this out will lead people to believe that I must oppose ready access to community care, pretrial diversion, alternative sentencing, mental health courts, or anything related to alternatives to incarceration.

That isn’t the case. Many problems require more than one solution. What I oppose is the idea that the solution has to be a simple dichotomous choice between arrest and incarceration versus community care. I’ve found discussions about criminalization of people with mental illnesses to be polarizing and unproductive. There will always be people with mental illnesses in jail and prison, because – like people with diabetes, heart disease, or AIDS – they sometimes commit very serious crimes. As a care provider, my view is that a patient’s need for treatment is independent of criminal culpability. An ill person deserves appropriate and skilled health care, regardless of the treatment setting. Moving someone from an understaffed, overcrowded correctional facility to an understaffed, overcrowded state hospital hardly solves the problem.

People make the argument that money spent on corrections would be better spent elsewhere, on services for at-risk youth, or on community substance abuse and mental health programs. I agree that all these programs are needed, but what rarely gets mentioned is that when money is diverted from jails and prisons, part of that money also includes funding for inmate health care. Taking away this money is like stealing a coat from a blind beggar in the winter time. If you want to make a serious problem worse, by all means, take away what little we have.

How much money are we talking here, anyway?

By some estimates, the money spent on health care for all American prisons is about $7.7 billion per year. That includes physician and related health care professional costs, laboratory and diagnostic testing, hospitalization costs, as well as medications. Fourteen percent of that, or about $1 billion, goes to mental health care. Those costs are expected to rise as the prison population continues to age. Meanwhile, federal spending on mandatory health care programs in 2013 was about $1 trillion. When the prison health care budget represents less than 1% of health care spending nationally, this doesn’t seem to be enough to be quibbling about and certainly not enough to be cutting or diverting elsewhere.

But of course, the correctional nihilists will respond, “You get what you pay for.” Inevitably, low-cost care becomes equivalent to low-quality care in the eyes of many Americans. But if you compare American medical outcomes globally, it’s been well established that we have fallen behind many countries in life expectancy and infant mortality, despite heavy investment in a broad spectrum of services and interventions.

Let’s compare that to prison. Because of data gathered through the 2000 Federal Death in Custody Reporting Act, as well as other studies, prisons have been able to demonstrate reduced mortality, compared with age-matched men in free society, particularly for minorities. That mortality rate doubles after release. Clearly, prisons appear to be keeping people alive more efficiently and at a fraction of the cost of our community services.

This is not to imply that incarceration should be the answer to every social problem. This is my response to the naysayers and nihilists who believe that jails and prisons are so far gone they are not worth investing in. The lives of many prisoners depend on that investment.

Dr. Hanson is a forensic psychiatrist and coauthor of Shrink Rap: Three Psychiatrists Explain Their Work. The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson’s employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

One serious problem with being an advocate of correctional mental health services is that you run the risk of coming across as an apologist, a Pollyanna, or a defender of the status quo. This is true even though every week I meet someone with an addiction problem so severe that he’d be unable to voluntarily seek or stay in treatment in the community. For someone like that, an arrest can be lifesaving. But to point this out will lead people to believe that I must oppose ready access to community care, pretrial diversion, alternative sentencing, mental health courts, or anything related to alternatives to incarceration.

That isn’t the case. Many problems require more than one solution. What I oppose is the idea that the solution has to be a simple dichotomous choice between arrest and incarceration versus community care. I’ve found discussions about criminalization of people with mental illnesses to be polarizing and unproductive. There will always be people with mental illnesses in jail and prison, because – like people with diabetes, heart disease, or AIDS – they sometimes commit very serious crimes. As a care provider, my view is that a patient’s need for treatment is independent of criminal culpability. An ill person deserves appropriate and skilled health care, regardless of the treatment setting. Moving someone from an understaffed, overcrowded correctional facility to an understaffed, overcrowded state hospital hardly solves the problem.

People make the argument that money spent on corrections would be better spent elsewhere, on services for at-risk youth, or on community substance abuse and mental health programs. I agree that all these programs are needed, but what rarely gets mentioned is that when money is diverted from jails and prisons, part of that money also includes funding for inmate health care. Taking away this money is like stealing a coat from a blind beggar in the winter time. If you want to make a serious problem worse, by all means, take away what little we have.

How much money are we talking here, anyway?

By some estimates, the money spent on health care for all American prisons is about $7.7 billion per year. That includes physician and related health care professional costs, laboratory and diagnostic testing, hospitalization costs, as well as medications. Fourteen percent of that, or about $1 billion, goes to mental health care. Those costs are expected to rise as the prison population continues to age. Meanwhile, federal spending on mandatory health care programs in 2013 was about $1 trillion. When the prison health care budget represents less than 1% of health care spending nationally, this doesn’t seem to be enough to be quibbling about and certainly not enough to be cutting or diverting elsewhere.

But of course, the correctional nihilists will respond, “You get what you pay for.” Inevitably, low-cost care becomes equivalent to low-quality care in the eyes of many Americans. But if you compare American medical outcomes globally, it’s been well established that we have fallen behind many countries in life expectancy and infant mortality, despite heavy investment in a broad spectrum of services and interventions.

Let’s compare that to prison. Because of data gathered through the 2000 Federal Death in Custody Reporting Act, as well as other studies, prisons have been able to demonstrate reduced mortality, compared with age-matched men in free society, particularly for minorities. That mortality rate doubles after release. Clearly, prisons appear to be keeping people alive more efficiently and at a fraction of the cost of our community services.

This is not to imply that incarceration should be the answer to every social problem. This is my response to the naysayers and nihilists who believe that jails and prisons are so far gone they are not worth investing in. The lives of many prisoners depend on that investment.

Dr. Hanson is a forensic psychiatrist and coauthor of Shrink Rap: Three Psychiatrists Explain Their Work. The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson’s employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

The influence of technology on the patient-physician relationship has been the subject of many discussions and publications. While a physician facing a computer screen throughout much of the office encounter is a vision no one believes is in the best interest of either the patient or the relationship, empathy as an admired professional trait and a successful tool in medicine is gaining support among the medical establishment. The question as to whether physicians can learn empathy has been examined. The benefits (real or potential) of digital technology in revitalizing this human interaction and technology’s potential to convey empathy must be considered. I will attempt to place some of these tools in a bit of a new light.

1. Encourage patients to utilize the patient portal.

Stage 2 of meaningful use requires that 5% of Medicare patients receive information via a patient portal; this has resulted in little less than an exercise in compliance. True interaction via the portal is not taking place. The catch-22 is that the portals provided by electronic health record (EHR) vendors are the least costly, but also the least useful. Providers are not enthusiastic about portals for good reason. Clinicians are fearful that office workflow cannot accommodate the potential volume of digital interactions. They also do not have the digital tools necessary to make the portal experience as beneficial as it can be.

Notwithstanding these barriers, I believe that a physician who encourages the use of the portal with conversations focused on patients’ participation in their own care will be seen as empathetic. Stressing the fact that the patient is being given a tool that delivers information (even if it is only a lab result) portrays the provider as a partner in care. The patient portal is the starting point of introducing patients to digital health technology. If it is the portal which is closest to the patient’s care touch point, other technologies will seem less intimidating and more relevant.

2. Prescribe apps and websites.

The days of a physician’s rolling eyes at a patient’s mention of information garnered on the Internet should be over. More than 90% of physicians use reference apps to treat patients. The power of digital technology to educate patients cannot be minimized. According to the Pew Research Internet Project (2013), one in three American adults have gone online to self-diagnose. Physicians agreed with that diagnosis 41% of the time. Is this reason to tout the Internet as a clinical diagnostician? I would hope not. However, it does demonstrate that the Digital Age of health care has arrived. It cannot be ignored. In the United Kingdom, the National Health Service will begin accrediting apps to be prescribed in 2015. If one thinks of patient education and self-monitoring instructions as important for patient care, then the natural extension of digitally delivering these tools should not send shock waves across the landscape. IMS Health offers technology for the prescribing of health apps and analytics for apps. Clearly, obstacles remain for app prescribing to enter mainstream medicine, the most significant being quality assurance regarding clinical effectiveness and data privacy and security. However, there are some excellent apps from which patients can benefit. In the nutritional arena, GoMeals and Fooducate are useful, as is Alivecor ECG for symptomatic heart rhythm monitoring. There are also several good smoking cessation apps. Further, there are text messaging programs which have proved not only popular but effective, specifically the smoking cessation offering SmokefreeTXT and the prenatal care program text4baby.

3. Participate in social media.

In 2010, the American Medical Association adopted guidelines for professionalism in social media. Among 22 other interesting statistics on health care in social media, are these two: More than 40% of consumers say that information found via social media affects the way they deal with their health, and 60% of social media users are the most likely to trust social media posts and activity by doctors over any other group.

4. Have your hospital start online patient support groups.

There are relative benefits to both in-person support groups and online patient support groups. My mother was a patient at a major cancer center, and I tweeted asking whether they had an online support group, as my mother enjoyed the in-person meetings, which she could no longer attend. The hospital account, having realized the importance of such outreach, responded with the establishment of an online group the following week. This type of patient service creates a sense of health care community, which is invaluable to both patient satisfaction and provider-patient relationships.

5. Utilize mobile technologies to facilitate patient engagement via self-monitoring.

The mere suggestion of recommending an app to have a patient log their blood pressure or follow their glucose is a signal of the importance of shared management and decision making. Apps that allow a person to track their activity or food consumption are simple yet meaningful. Patients are longing for tools they can use themselves or utilize as caregivers.

Empathy can be conveyed directly as emotional support or indirectly with actions described above. It is ironic that technology, cold and inhumane in a solitary context, can be transformed and seen as empathetic if it is offered in a humanistic way.

Dr. Scher is an electrophysiologist with the Heart Group of Lancaster (Pa.) General Health. He is also director of DLS Healthcare Consulting, Harrisburg, Pa., and clinical associate professor of medicine at the Pennsylvania State University, Hershey.

The influence of technology on the patient-physician relationship has been the subject of many discussions and publications. While a physician facing a computer screen throughout much of the office encounter is a vision no one believes is in the best interest of either the patient or the relationship, empathy as an admired professional trait and a successful tool in medicine is gaining support among the medical establishment. The question as to whether physicians can learn empathy has been examined. The benefits (real or potential) of digital technology in revitalizing this human interaction and technology’s potential to convey empathy must be considered. I will attempt to place some of these tools in a bit of a new light.

1. Encourage patients to utilize the patient portal.

Stage 2 of meaningful use requires that 5% of Medicare patients receive information via a patient portal; this has resulted in little less than an exercise in compliance. True interaction via the portal is not taking place. The catch-22 is that the portals provided by electronic health record (EHR) vendors are the least costly, but also the least useful. Providers are not enthusiastic about portals for good reason. Clinicians are fearful that office workflow cannot accommodate the potential volume of digital interactions. They also do not have the digital tools necessary to make the portal experience as beneficial as it can be.

Notwithstanding these barriers, I believe that a physician who encourages the use of the portal with conversations focused on patients’ participation in their own care will be seen as empathetic. Stressing the fact that the patient is being given a tool that delivers information (even if it is only a lab result) portrays the provider as a partner in care. The patient portal is the starting point of introducing patients to digital health technology. If it is the portal which is closest to the patient’s care touch point, other technologies will seem less intimidating and more relevant.

2. Prescribe apps and websites.

The days of a physician’s rolling eyes at a patient’s mention of information garnered on the Internet should be over. More than 90% of physicians use reference apps to treat patients. The power of digital technology to educate patients cannot be minimized. According to the Pew Research Internet Project (2013), one in three American adults have gone online to self-diagnose. Physicians agreed with that diagnosis 41% of the time. Is this reason to tout the Internet as a clinical diagnostician? I would hope not. However, it does demonstrate that the Digital Age of health care has arrived. It cannot be ignored. In the United Kingdom, the National Health Service will begin accrediting apps to be prescribed in 2015. If one thinks of patient education and self-monitoring instructions as important for patient care, then the natural extension of digitally delivering these tools should not send shock waves across the landscape. IMS Health offers technology for the prescribing of health apps and analytics for apps. Clearly, obstacles remain for app prescribing to enter mainstream medicine, the most significant being quality assurance regarding clinical effectiveness and data privacy and security. However, there are some excellent apps from which patients can benefit. In the nutritional arena, GoMeals and Fooducate are useful, as is Alivecor ECG for symptomatic heart rhythm monitoring. There are also several good smoking cessation apps. Further, there are text messaging programs which have proved not only popular but effective, specifically the smoking cessation offering SmokefreeTXT and the prenatal care program text4baby.

3. Participate in social media.

In 2010, the American Medical Association adopted guidelines for professionalism in social media. Among 22 other interesting statistics on health care in social media, are these two: More than 40% of consumers say that information found via social media affects the way they deal with their health, and 60% of social media users are the most likely to trust social media posts and activity by doctors over any other group.

4. Have your hospital start online patient support groups.

There are relative benefits to both in-person support groups and online patient support groups. My mother was a patient at a major cancer center, and I tweeted asking whether they had an online support group, as my mother enjoyed the in-person meetings, which she could no longer attend. The hospital account, having realized the importance of such outreach, responded with the establishment of an online group the following week. This type of patient service creates a sense of health care community, which is invaluable to both patient satisfaction and provider-patient relationships.

5. Utilize mobile technologies to facilitate patient engagement via self-monitoring.

The mere suggestion of recommending an app to have a patient log their blood pressure or follow their glucose is a signal of the importance of shared management and decision making. Apps that allow a person to track their activity or food consumption are simple yet meaningful. Patients are longing for tools they can use themselves or utilize as caregivers.

Empathy can be conveyed directly as emotional support or indirectly with actions described above. It is ironic that technology, cold and inhumane in a solitary context, can be transformed and seen as empathetic if it is offered in a humanistic way.

Dr. Scher is an electrophysiologist with the Heart Group of Lancaster (Pa.) General Health. He is also director of DLS Healthcare Consulting, Harrisburg, Pa., and clinical associate professor of medicine at the Pennsylvania State University, Hershey.

The influence of technology on the patient-physician relationship has been the subject of many discussions and publications. While a physician facing a computer screen throughout much of the office encounter is a vision no one believes is in the best interest of either the patient or the relationship, empathy as an admired professional trait and a successful tool in medicine is gaining support among the medical establishment. The question as to whether physicians can learn empathy has been examined. The benefits (real or potential) of digital technology in revitalizing this human interaction and technology’s potential to convey empathy must be considered. I will attempt to place some of these tools in a bit of a new light.

1. Encourage patients to utilize the patient portal.

Stage 2 of meaningful use requires that 5% of Medicare patients receive information via a patient portal; this has resulted in little less than an exercise in compliance. True interaction via the portal is not taking place. The catch-22 is that the portals provided by electronic health record (EHR) vendors are the least costly, but also the least useful. Providers are not enthusiastic about portals for good reason. Clinicians are fearful that office workflow cannot accommodate the potential volume of digital interactions. They also do not have the digital tools necessary to make the portal experience as beneficial as it can be.

Notwithstanding these barriers, I believe that a physician who encourages the use of the portal with conversations focused on patients’ participation in their own care will be seen as empathetic. Stressing the fact that the patient is being given a tool that delivers information (even if it is only a lab result) portrays the provider as a partner in care. The patient portal is the starting point of introducing patients to digital health technology. If it is the portal which is closest to the patient’s care touch point, other technologies will seem less intimidating and more relevant.

2. Prescribe apps and websites.

The days of a physician’s rolling eyes at a patient’s mention of information garnered on the Internet should be over. More than 90% of physicians use reference apps to treat patients. The power of digital technology to educate patients cannot be minimized. According to the Pew Research Internet Project (2013), one in three American adults have gone online to self-diagnose. Physicians agreed with that diagnosis 41% of the time. Is this reason to tout the Internet as a clinical diagnostician? I would hope not. However, it does demonstrate that the Digital Age of health care has arrived. It cannot be ignored. In the United Kingdom, the National Health Service will begin accrediting apps to be prescribed in 2015. If one thinks of patient education and self-monitoring instructions as important for patient care, then the natural extension of digitally delivering these tools should not send shock waves across the landscape. IMS Health offers technology for the prescribing of health apps and analytics for apps. Clearly, obstacles remain for app prescribing to enter mainstream medicine, the most significant being quality assurance regarding clinical effectiveness and data privacy and security. However, there are some excellent apps from which patients can benefit. In the nutritional arena, GoMeals and Fooducate are useful, as is Alivecor ECG for symptomatic heart rhythm monitoring. There are also several good smoking cessation apps. Further, there are text messaging programs which have proved not only popular but effective, specifically the smoking cessation offering SmokefreeTXT and the prenatal care program text4baby.

3. Participate in social media.

In 2010, the American Medical Association adopted guidelines for professionalism in social media. Among 22 other interesting statistics on health care in social media, are these two: More than 40% of consumers say that information found via social media affects the way they deal with their health, and 60% of social media users are the most likely to trust social media posts and activity by doctors over any other group.

4. Have your hospital start online patient support groups.

There are relative benefits to both in-person support groups and online patient support groups. My mother was a patient at a major cancer center, and I tweeted asking whether they had an online support group, as my mother enjoyed the in-person meetings, which she could no longer attend. The hospital account, having realized the importance of such outreach, responded with the establishment of an online group the following week. This type of patient service creates a sense of health care community, which is invaluable to both patient satisfaction and provider-patient relationships.

5. Utilize mobile technologies to facilitate patient engagement via self-monitoring.

The mere suggestion of recommending an app to have a patient log their blood pressure or follow their glucose is a signal of the importance of shared management and decision making. Apps that allow a person to track their activity or food consumption are simple yet meaningful. Patients are longing for tools they can use themselves or utilize as caregivers.

Empathy can be conveyed directly as emotional support or indirectly with actions described above. It is ironic that technology, cold and inhumane in a solitary context, can be transformed and seen as empathetic if it is offered in a humanistic way.

Dr. Scher is an electrophysiologist with the Heart Group of Lancaster (Pa.) General Health. He is also director of DLS Healthcare Consulting, Harrisburg, Pa., and clinical associate professor of medicine at the Pennsylvania State University, Hershey.

BOSTON – A nonsteroidal anti-inflammatory drug and exercise may be enough to control active axial spondyloarthritis in some patients, suggest authors of draft guidelines on the management of patients with the condition.

The guidelines, not ready for prime time, have yet to be reviewed or endorsed by the American College of Rheumatology (ACR) and the Spondylitis Association of America, or the SpondyloArthritis Research and Treatment Network (SPARTAN), and are subject to change, emphasized Dr. Michael M. Ward, senior investigator at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

With that caveat in mind, Dr. Ward presented a sneak peek at the guidelines to a standing-room only crowd at the ACR annual meeting in Boston.

Some definitions

The guidelines offer recommendations on the management of patients with active and stable ankylosing spondylitis (AS) and axial spondyloarthropathies (axSpA) that are symptomatic but without radiographic evidence (nonradiographic, or nr-axSpA).

Active AS is defined as disease that causes symptoms at an unacceptably burdensome level as reported by the patient that are judged by the examining clinician to be caused by AS. The same definition also applies to nr-axSpA.

Stable disease is defined as either an asymptomatic state or symptoms that were previously bothersome but are currently at an acceptable level as reported by the patient. The patient had to have had bothersome symptoms for at least 6 months before entering the stable disease state. This definition is also applicable to stable nr-axSpA.

The investigators considered the best available evidence on the use of NSAIDs (running the gamut from aspirin to tolmetin), slow-acting antirheumatic agents such as methotrexate, glucocorticoids (prednisone and others), tumor necrosis factor (TNF) inhibitors, such as adalimumab, etanercept, and others), and non-TNF biologic agents (abatacept, rituximab, tocilizumab, and others).

Active AS

Dr. Ward presented a management flow tree for patients with active AS, starting with a strong recommendation for an NSAID, conditionally recommended to be used continuously. The authors felt, however, that there was not enough evidence to support the use of one NSAID over another. They also strongly recommended physical therapy, with less robust recommendations for active than for passive exercise and for exercises performed in water rather than on land. The latter recommendation is based on the fact that, although water-based exercises have been shown to be as good as or better than dry land exercises for relieving symptoms, water-based exercise may be impractical for many patients, Dr. Ward noted.

For patients whose disease remains active despite NSAIDs and exercise, the committee strongly recommends use of a tumor necrosis factor inhibitor (TNFi) (no specific agent preferred). If a patient on a TNFi has recurrent iritis, the guidelines have a conditional recommendation for the use of infliximab or adalimumab. For patients with inflammatory bowel disease (IBD), the authors conditionally recommend a TNFi monoclonal antibody as opposed to etanercept.

If the disease remains active on a TNFi, an alternative TNFi can be considered.

“For patients who have contraindications to TNF inhibitors, we considered the choice between adding a slow-acting drug such as sulfasalazine or pamidronate or treating with a non-TNF biologic. Of course, there are no head-to-head trials between those two options, so based on the indirect evidence that’s available, the committee voted for a conditional recommendation against the use of a non-TNF biologic in favor of a slow-acting drug in that setting,” Dr. Ward said.

If there are no contraindications to a TNF inhibitor, however, the committee strongly favored the use of a TNF inhibitor over a slow-acting agent, he emphasized.

For patients who have isolated sacroiliitis, peripheral arthritis, or enthesis, the committee provisionally recommends local injection of a glucocorticoid, with cautions to use infrequently and only if two or fewer joints are involved in peripheral arthritis, and avoidance of injection of the Achilles, patellar, or quadriceps tendons in patients with enthesitis.

For all patients, the guidelines half-heartedly recommend monitoring validated axSpA disease activity measures and C-reactive protein and erythrocyte sedimentation rate (ESR). The group also conditionally supported unsupervised back exercises, formal group or individual self-management education, and fall evaluation and counseling.

Committee members strongly felt that systemic glucocorticoids should not be used in patients with active axSpA, except in cases where a short-term course with quick taper may be helpful, such as in patients with peripheral flare, or during pregnancy or a concomitant IBD flare.

Stable AS

“For patients with stable ankylosing spondylitis who are on combination therapy, either combination therapy with NSAIDs and a TNF inhibitor, or a slow-acting drug and a TNF inhibitor, the committee voted against continuation of a combination in favor of TNF monotherapy. It’s a conditional recommendation, so there certainly would be situations where one would not want to do that, but in general the committee thought that was the preferable approach, balancing the benefits and potential risks of combination therapy against monotherapy in patients with stable AS,” Dr. Ward said.

The committee members strongly supported physical therapy in patients with stable AS and gave a conditional nod to monitoring, back exercises, group support, and fall counseling.

For patients with stable AS and advanced hip arthritis, hip replacement is strongly recommended. Recommendations for and against other special conditions include severe kyphosis (strongly against elective spine osteotomy except in specialized centers), acute iritis (strong support for an ophthalmology consultant), recurrent iritis (conditional support for at home use of a topical glucocorticoid under the supervision of an eye care provider, and use of infliximab or adalimumab over etanercept), and IBD (strong recommendation for TNFi monoclonals over etanercept and conditional endorsement of no preferred NSAID).

Active nr-axSpA

Recommendations for the treatment of nr-axSpA are essentially identical to those for treating active AS, Dr. Ward noted, except that in contrast to active AS, where the recommendation is strongly in favor of TNF inhibitors, the committee gave only a conditional recommendation for the use of a TNF inhibitor in this clinical situation.

Stable nr-axSpA

For patients with stable nr-axSpA, the recommendations are strongly in favor of NSAID use, with a conditional suggestion to use on demand. The recommendations also are conditionally against combination therapy with either an NSAID or slow-acting agent plus a TNF inhibitor, with a conditional approval for TNF inhibitor monotherapy instead. The committee strongly supported physical therapy for these patients and gave a lukewarm embrace of monitoring for disease activity, CRP, or ESR.

Dr. Ward noted that the guidelines are designed to help clinicians with treatment decisions for the typical patient with AS or nr-axSpA, and do not address the needs of all populations or all clinical circumstances or contingencies.

He also noted that for many of the questions the committee members tried to address, high-quality evidence was limited.

Dr. Ward did not mention a projected publication date for the guidelines. He had no relevant financial conflicts to disclose.

BOSTON – A nonsteroidal anti-inflammatory drug and exercise may be enough to control active axial spondyloarthritis in some patients, suggest authors of draft guidelines on the management of patients with the condition.

The guidelines, not ready for prime time, have yet to be reviewed or endorsed by the American College of Rheumatology (ACR) and the Spondylitis Association of America, or the SpondyloArthritis Research and Treatment Network (SPARTAN), and are subject to change, emphasized Dr. Michael M. Ward, senior investigator at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

With that caveat in mind, Dr. Ward presented a sneak peek at the guidelines to a standing-room only crowd at the ACR annual meeting in Boston.

Some definitions

The guidelines offer recommendations on the management of patients with active and stable ankylosing spondylitis (AS) and axial spondyloarthropathies (axSpA) that are symptomatic but without radiographic evidence (nonradiographic, or nr-axSpA).

Active AS is defined as disease that causes symptoms at an unacceptably burdensome level as reported by the patient that are judged by the examining clinician to be caused by AS. The same definition also applies to nr-axSpA.

Stable disease is defined as either an asymptomatic state or symptoms that were previously bothersome but are currently at an acceptable level as reported by the patient. The patient had to have had bothersome symptoms for at least 6 months before entering the stable disease state. This definition is also applicable to stable nr-axSpA.

The investigators considered the best available evidence on the use of NSAIDs (running the gamut from aspirin to tolmetin), slow-acting antirheumatic agents such as methotrexate, glucocorticoids (prednisone and others), tumor necrosis factor (TNF) inhibitors, such as adalimumab, etanercept, and others), and non-TNF biologic agents (abatacept, rituximab, tocilizumab, and others).

Active AS

Dr. Ward presented a management flow tree for patients with active AS, starting with a strong recommendation for an NSAID, conditionally recommended to be used continuously. The authors felt, however, that there was not enough evidence to support the use of one NSAID over another. They also strongly recommended physical therapy, with less robust recommendations for active than for passive exercise and for exercises performed in water rather than on land. The latter recommendation is based on the fact that, although water-based exercises have been shown to be as good as or better than dry land exercises for relieving symptoms, water-based exercise may be impractical for many patients, Dr. Ward noted.

For patients whose disease remains active despite NSAIDs and exercise, the committee strongly recommends use of a tumor necrosis factor inhibitor (TNFi) (no specific agent preferred). If a patient on a TNFi has recurrent iritis, the guidelines have a conditional recommendation for the use of infliximab or adalimumab. For patients with inflammatory bowel disease (IBD), the authors conditionally recommend a TNFi monoclonal antibody as opposed to etanercept.

If the disease remains active on a TNFi, an alternative TNFi can be considered.

“For patients who have contraindications to TNF inhibitors, we considered the choice between adding a slow-acting drug such as sulfasalazine or pamidronate or treating with a non-TNF biologic. Of course, there are no head-to-head trials between those two options, so based on the indirect evidence that’s available, the committee voted for a conditional recommendation against the use of a non-TNF biologic in favor of a slow-acting drug in that setting,” Dr. Ward said.

If there are no contraindications to a TNF inhibitor, however, the committee strongly favored the use of a TNF inhibitor over a slow-acting agent, he emphasized.

For patients who have isolated sacroiliitis, peripheral arthritis, or enthesis, the committee provisionally recommends local injection of a glucocorticoid, with cautions to use infrequently and only if two or fewer joints are involved in peripheral arthritis, and avoidance of injection of the Achilles, patellar, or quadriceps tendons in patients with enthesitis.

For all patients, the guidelines half-heartedly recommend monitoring validated axSpA disease activity measures and C-reactive protein and erythrocyte sedimentation rate (ESR). The group also conditionally supported unsupervised back exercises, formal group or individual self-management education, and fall evaluation and counseling.

Committee members strongly felt that systemic glucocorticoids should not be used in patients with active axSpA, except in cases where a short-term course with quick taper may be helpful, such as in patients with peripheral flare, or during pregnancy or a concomitant IBD flare.

Stable AS

“For patients with stable ankylosing spondylitis who are on combination therapy, either combination therapy with NSAIDs and a TNF inhibitor, or a slow-acting drug and a TNF inhibitor, the committee voted against continuation of a combination in favor of TNF monotherapy. It’s a conditional recommendation, so there certainly would be situations where one would not want to do that, but in general the committee thought that was the preferable approach, balancing the benefits and potential risks of combination therapy against monotherapy in patients with stable AS,” Dr. Ward said.

The committee members strongly supported physical therapy in patients with stable AS and gave a conditional nod to monitoring, back exercises, group support, and fall counseling.

For patients with stable AS and advanced hip arthritis, hip replacement is strongly recommended. Recommendations for and against other special conditions include severe kyphosis (strongly against elective spine osteotomy except in specialized centers), acute iritis (strong support for an ophthalmology consultant), recurrent iritis (conditional support for at home use of a topical glucocorticoid under the supervision of an eye care provider, and use of infliximab or adalimumab over etanercept), and IBD (strong recommendation for TNFi monoclonals over etanercept and conditional endorsement of no preferred NSAID).

Active nr-axSpA

Recommendations for the treatment of nr-axSpA are essentially identical to those for treating active AS, Dr. Ward noted, except that in contrast to active AS, where the recommendation is strongly in favor of TNF inhibitors, the committee gave only a conditional recommendation for the use of a TNF inhibitor in this clinical situation.

Stable nr-axSpA

For patients with stable nr-axSpA, the recommendations are strongly in favor of NSAID use, with a conditional suggestion to use on demand. The recommendations also are conditionally against combination therapy with either an NSAID or slow-acting agent plus a TNF inhibitor, with a conditional approval for TNF inhibitor monotherapy instead. The committee strongly supported physical therapy for these patients and gave a lukewarm embrace of monitoring for disease activity, CRP, or ESR.

Dr. Ward noted that the guidelines are designed to help clinicians with treatment decisions for the typical patient with AS or nr-axSpA, and do not address the needs of all populations or all clinical circumstances or contingencies.

He also noted that for many of the questions the committee members tried to address, high-quality evidence was limited.

Dr. Ward did not mention a projected publication date for the guidelines. He had no relevant financial conflicts to disclose.

BOSTON – A nonsteroidal anti-inflammatory drug and exercise may be enough to control active axial spondyloarthritis in some patients, suggest authors of draft guidelines on the management of patients with the condition.

The guidelines, not ready for prime time, have yet to be reviewed or endorsed by the American College of Rheumatology (ACR) and the Spondylitis Association of America, or the SpondyloArthritis Research and Treatment Network (SPARTAN), and are subject to change, emphasized Dr. Michael M. Ward, senior investigator at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

With that caveat in mind, Dr. Ward presented a sneak peek at the guidelines to a standing-room only crowd at the ACR annual meeting in Boston.

Some definitions

The guidelines offer recommendations on the management of patients with active and stable ankylosing spondylitis (AS) and axial spondyloarthropathies (axSpA) that are symptomatic but without radiographic evidence (nonradiographic, or nr-axSpA).

Active AS is defined as disease that causes symptoms at an unacceptably burdensome level as reported by the patient that are judged by the examining clinician to be caused by AS. The same definition also applies to nr-axSpA.

Stable disease is defined as either an asymptomatic state or symptoms that were previously bothersome but are currently at an acceptable level as reported by the patient. The patient had to have had bothersome symptoms for at least 6 months before entering the stable disease state. This definition is also applicable to stable nr-axSpA.

The investigators considered the best available evidence on the use of NSAIDs (running the gamut from aspirin to tolmetin), slow-acting antirheumatic agents such as methotrexate, glucocorticoids (prednisone and others), tumor necrosis factor (TNF) inhibitors, such as adalimumab, etanercept, and others), and non-TNF biologic agents (abatacept, rituximab, tocilizumab, and others).

Active AS

Dr. Ward presented a management flow tree for patients with active AS, starting with a strong recommendation for an NSAID, conditionally recommended to be used continuously. The authors felt, however, that there was not enough evidence to support the use of one NSAID over another. They also strongly recommended physical therapy, with less robust recommendations for active than for passive exercise and for exercises performed in water rather than on land. The latter recommendation is based on the fact that, although water-based exercises have been shown to be as good as or better than dry land exercises for relieving symptoms, water-based exercise may be impractical for many patients, Dr. Ward noted.

For patients whose disease remains active despite NSAIDs and exercise, the committee strongly recommends use of a tumor necrosis factor inhibitor (TNFi) (no specific agent preferred). If a patient on a TNFi has recurrent iritis, the guidelines have a conditional recommendation for the use of infliximab or adalimumab. For patients with inflammatory bowel disease (IBD), the authors conditionally recommend a TNFi monoclonal antibody as opposed to etanercept.

If the disease remains active on a TNFi, an alternative TNFi can be considered.

“For patients who have contraindications to TNF inhibitors, we considered the choice between adding a slow-acting drug such as sulfasalazine or pamidronate or treating with a non-TNF biologic. Of course, there are no head-to-head trials between those two options, so based on the indirect evidence that’s available, the committee voted for a conditional recommendation against the use of a non-TNF biologic in favor of a slow-acting drug in that setting,” Dr. Ward said.

If there are no contraindications to a TNF inhibitor, however, the committee strongly favored the use of a TNF inhibitor over a slow-acting agent, he emphasized.

For patients who have isolated sacroiliitis, peripheral arthritis, or enthesis, the committee provisionally recommends local injection of a glucocorticoid, with cautions to use infrequently and only if two or fewer joints are involved in peripheral arthritis, and avoidance of injection of the Achilles, patellar, or quadriceps tendons in patients with enthesitis.

For all patients, the guidelines half-heartedly recommend monitoring validated axSpA disease activity measures and C-reactive protein and erythrocyte sedimentation rate (ESR). The group also conditionally supported unsupervised back exercises, formal group or individual self-management education, and fall evaluation and counseling.

Committee members strongly felt that systemic glucocorticoids should not be used in patients with active axSpA, except in cases where a short-term course with quick taper may be helpful, such as in patients with peripheral flare, or during pregnancy or a concomitant IBD flare.

Stable AS

“For patients with stable ankylosing spondylitis who are on combination therapy, either combination therapy with NSAIDs and a TNF inhibitor, or a slow-acting drug and a TNF inhibitor, the committee voted against continuation of a combination in favor of TNF monotherapy. It’s a conditional recommendation, so there certainly would be situations where one would not want to do that, but in general the committee thought that was the preferable approach, balancing the benefits and potential risks of combination therapy against monotherapy in patients with stable AS,” Dr. Ward said.

The committee members strongly supported physical therapy in patients with stable AS and gave a conditional nod to monitoring, back exercises, group support, and fall counseling.

For patients with stable AS and advanced hip arthritis, hip replacement is strongly recommended. Recommendations for and against other special conditions include severe kyphosis (strongly against elective spine osteotomy except in specialized centers), acute iritis (strong support for an ophthalmology consultant), recurrent iritis (conditional support for at home use of a topical glucocorticoid under the supervision of an eye care provider, and use of infliximab or adalimumab over etanercept), and IBD (strong recommendation for TNFi monoclonals over etanercept and conditional endorsement of no preferred NSAID).

Active nr-axSpA

Recommendations for the treatment of nr-axSpA are essentially identical to those for treating active AS, Dr. Ward noted, except that in contrast to active AS, where the recommendation is strongly in favor of TNF inhibitors, the committee gave only a conditional recommendation for the use of a TNF inhibitor in this clinical situation.

Stable nr-axSpA

For patients with stable nr-axSpA, the recommendations are strongly in favor of NSAID use, with a conditional suggestion to use on demand. The recommendations also are conditionally against combination therapy with either an NSAID or slow-acting agent plus a TNF inhibitor, with a conditional approval for TNF inhibitor monotherapy instead. The committee strongly supported physical therapy for these patients and gave a lukewarm embrace of monitoring for disease activity, CRP, or ESR.

Dr. Ward noted that the guidelines are designed to help clinicians with treatment decisions for the typical patient with AS or nr-axSpA, and do not address the needs of all populations or all clinical circumstances or contingencies.

He also noted that for many of the questions the committee members tried to address, high-quality evidence was limited.

Dr. Ward did not mention a projected publication date for the guidelines. He had no relevant financial conflicts to disclose.

Daniel Pollyea, MD

Credit: University of Colorado

BARCELONA—An agent that inhibits isocitrate dehydrogenase (IDH) 1 shows the potential to transform therapy for certain patients with acute myeloid leukemia (AML), according to a speaker at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics.

The drug, known as AG-120, demonstrated clinical activity and was considered to be well-tolerated in a phase 1 study of patients with advanced, IDH1 mutant-positive AML.

Daniel Pollyea, MD, of the University of Colorado School of Medicine in Aurora, presented data on AG-120 at the symposium as abstract LBA1. The research was sponsored by Agios Pharmaceuticals, makers of AG-120.

“This is the first study in humans of an inhibitor of mutant IDH1 and the first demonstration of clinical activity of AG-120 in AML patients whose cancers have the IDH1 mutation,” Dr Pollyea said. “Although the data are early, we are encouraged to see evidence of clinical activity, as the primary objectives of phase 1 studies are to determine safety and tolerability.”

Dr Pollyea noted that mutations in IDH1 lead to a cascade of metabolic events that contribute to malignancy. Mutant IDH1 produces an excess amount of 2-hydroxyglutarate (2-HG), which prevents cells from maturing into normal, functioning cells, and this leads to malignancy.

In this study, the researchers found that AG-120 reduced 2-HG levels in diseased cells to normal levels, allowing them to mature into normal cells.

The trial included 17 patients with relapsed and/or refractory AML, who had received a median of 2 prior treatments. Patients were scheduled to

receive AG-120 in 1 of 4 dose groups: 100 mg twice a day, 300 mg once a day, 500 mg once a day, and 800 mg once a day over continuous 28-day cycles.

Fourteen patients were evaluable for response, and 7 responded. Four patients achieved a complete response, 2 had a complete response in the marrow, and 1 had a partial response.

Responses occurred at all the dose levels tested. In the 4 patients who achieved a complete response, there was early evidence of durability, ranging from 15 days to 5 months. All responding patients remain on AG-120, and 1 patient with stable disease remains on the drug.

“AML is a devastating disease that has historically been very difficult to treat, and these findings suggest that AG-120 has the potential to transform therapy for patients with IDH1-mutant positive AML,” Dr Pollyea said.

He and his colleagues also found that AG-120 was generally well-tolerated. The majority of adverse events were grade 1 and 2. The most common of these were nausea, fatigue, and dyspnea.

Eight patients experienced serious adverse events, but these were primarily related to disease progression.

One patient experienced a dose-limiting toxicity of asymptomatic grade 3 QT prolongation at the highest dose tested to date, which improved to grade 1 with dose reduction. This patient is in complete remission and remains on AG-120.

The maximum-tolerated dose of AG-120 has not been reached.

There were 6 patient deaths, all unrelated to AG-120. Five deaths occurred after patients discontinued treatment due to progressive disease, and 1 patient died due to disease-related intracranial hemorrhage while on treatment.

Dr Pollyea and his colleagues are continuing this study with the aim of fully understanding the safety of the drug, determining the maximum-tolerated dose, and assessing its efficacy in treating AML and myelodysplastic syndromes.

Daniel Pollyea, MD

Credit: University of Colorado

BARCELONA—An agent that inhibits isocitrate dehydrogenase (IDH) 1 shows the potential to transform therapy for certain patients with acute myeloid leukemia (AML), according to a speaker at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics.

The drug, known as AG-120, demonstrated clinical activity and was considered to be well-tolerated in a phase 1 study of patients with advanced, IDH1 mutant-positive AML.

Daniel Pollyea, MD, of the University of Colorado School of Medicine in Aurora, presented data on AG-120 at the symposium as abstract LBA1. The research was sponsored by Agios Pharmaceuticals, makers of AG-120.

“This is the first study in humans of an inhibitor of mutant IDH1 and the first demonstration of clinical activity of AG-120 in AML patients whose cancers have the IDH1 mutation,” Dr Pollyea said. “Although the data are early, we are encouraged to see evidence of clinical activity, as the primary objectives of phase 1 studies are to determine safety and tolerability.”

Dr Pollyea noted that mutations in IDH1 lead to a cascade of metabolic events that contribute to malignancy. Mutant IDH1 produces an excess amount of 2-hydroxyglutarate (2-HG), which prevents cells from maturing into normal, functioning cells, and this leads to malignancy.

In this study, the researchers found that AG-120 reduced 2-HG levels in diseased cells to normal levels, allowing them to mature into normal cells.

The trial included 17 patients with relapsed and/or refractory AML, who had received a median of 2 prior treatments. Patients were scheduled to

receive AG-120 in 1 of 4 dose groups: 100 mg twice a day, 300 mg once a day, 500 mg once a day, and 800 mg once a day over continuous 28-day cycles.

Fourteen patients were evaluable for response, and 7 responded. Four patients achieved a complete response, 2 had a complete response in the marrow, and 1 had a partial response.

Responses occurred at all the dose levels tested. In the 4 patients who achieved a complete response, there was early evidence of durability, ranging from 15 days to 5 months. All responding patients remain on AG-120, and 1 patient with stable disease remains on the drug.

“AML is a devastating disease that has historically been very difficult to treat, and these findings suggest that AG-120 has the potential to transform therapy for patients with IDH1-mutant positive AML,” Dr Pollyea said.

He and his colleagues also found that AG-120 was generally well-tolerated. The majority of adverse events were grade 1 and 2. The most common of these were nausea, fatigue, and dyspnea.

Eight patients experienced serious adverse events, but these were primarily related to disease progression.

One patient experienced a dose-limiting toxicity of asymptomatic grade 3 QT prolongation at the highest dose tested to date, which improved to grade 1 with dose reduction. This patient is in complete remission and remains on AG-120.

The maximum-tolerated dose of AG-120 has not been reached.

There were 6 patient deaths, all unrelated to AG-120. Five deaths occurred after patients discontinued treatment due to progressive disease, and 1 patient died due to disease-related intracranial hemorrhage while on treatment.

Dr Pollyea and his colleagues are continuing this study with the aim of fully understanding the safety of the drug, determining the maximum-tolerated dose, and assessing its efficacy in treating AML and myelodysplastic syndromes.

Daniel Pollyea, MD

Credit: University of Colorado

BARCELONA—An agent that inhibits isocitrate dehydrogenase (IDH) 1 shows the potential to transform therapy for certain patients with acute myeloid leukemia (AML), according to a speaker at the 26th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics.

The drug, known as AG-120, demonstrated clinical activity and was considered to be well-tolerated in a phase 1 study of patients with advanced, IDH1 mutant-positive AML.

Daniel Pollyea, MD, of the University of Colorado School of Medicine in Aurora, presented data on AG-120 at the symposium as abstract LBA1. The research was sponsored by Agios Pharmaceuticals, makers of AG-120.

“This is the first study in humans of an inhibitor of mutant IDH1 and the first demonstration of clinical activity of AG-120 in AML patients whose cancers have the IDH1 mutation,” Dr Pollyea said. “Although the data are early, we are encouraged to see evidence of clinical activity, as the primary objectives of phase 1 studies are to determine safety and tolerability.”

Dr Pollyea noted that mutations in IDH1 lead to a cascade of metabolic events that contribute to malignancy. Mutant IDH1 produces an excess amount of 2-hydroxyglutarate (2-HG), which prevents cells from maturing into normal, functioning cells, and this leads to malignancy.

In this study, the researchers found that AG-120 reduced 2-HG levels in diseased cells to normal levels, allowing them to mature into normal cells.

The trial included 17 patients with relapsed and/or refractory AML, who had received a median of 2 prior treatments. Patients were scheduled to

receive AG-120 in 1 of 4 dose groups: 100 mg twice a day, 300 mg once a day, 500 mg once a day, and 800 mg once a day over continuous 28-day cycles.

Fourteen patients were evaluable for response, and 7 responded. Four patients achieved a complete response, 2 had a complete response in the marrow, and 1 had a partial response.

Responses occurred at all the dose levels tested. In the 4 patients who achieved a complete response, there was early evidence of durability, ranging from 15 days to 5 months. All responding patients remain on AG-120, and 1 patient with stable disease remains on the drug.

“AML is a devastating disease that has historically been very difficult to treat, and these findings suggest that AG-120 has the potential to transform therapy for patients with IDH1-mutant positive AML,” Dr Pollyea said.

He and his colleagues also found that AG-120 was generally well-tolerated. The majority of adverse events were grade 1 and 2. The most common of these were nausea, fatigue, and dyspnea.

Eight patients experienced serious adverse events, but these were primarily related to disease progression.

One patient experienced a dose-limiting toxicity of asymptomatic grade 3 QT prolongation at the highest dose tested to date, which improved to grade 1 with dose reduction. This patient is in complete remission and remains on AG-120.

The maximum-tolerated dose of AG-120 has not been reached.

There were 6 patient deaths, all unrelated to AG-120. Five deaths occurred after patients discontinued treatment due to progressive disease, and 1 patient died due to disease-related intracranial hemorrhage while on treatment.

Dr Pollyea and his colleagues are continuing this study with the aim of fully understanding the safety of the drug, determining the maximum-tolerated dose, and assessing its efficacy in treating AML and myelodysplastic syndromes.

Lab mice

Credit: Aaron Logan

Scientists have long known that mice are not perfect models for studying conditions in humans, but new research reveals why certain processes and systems in

mice are so different from those in humans.

As part of the mouse ENCODE project, researchers discovered that a significant number of mouse genes do not behave like their human counterparts.

This suggests scientists will need to rethink at least some roles of the lab mouse as a model organism.

“There are a substantial number of mouse genes that are regulated in ways different from similar genes in humans,” said Bing Ren, PhD, of the University of California, San Diego.

“The differences are not random. They are clustered along certain pathways, such as in genes regulating the immune system.”

The findings, part of a series of related papers being published in Nature, Science, and other journals (see below), are derived from the ongoing mouse ENCODE (Encyclopedia of DNA Elements) project.

This multi-institution effort was launched in 2007 to build a comprehensive list of functional elements of the mouse genome. It complements the earlier human ENCODE project, which published its functional catalogue in 2012.

“Both the original human and mouse genome projects gave us the sequence of genetic letters that comprise each organism but no idea how they worked or worked together to create and sustain life,” Dr Ren said.

“The human ENCODE project was designed to answer some of those questions. The mouse ENCODE project is its complement. It’s intended to provide scientists with comprehensive annotation of what mouse genes do, information that may ultimately be used for human therapeutic purposes.”

Only half of human genomic DNA aligns to mouse genomic DNA. But protein-coding genes, which provide the actionable instructions to build a living organism, are more strongly conserved across the two species.

Mice and humans share approximately 70% of the same protein-coding gene sequences, though these genes constitute just 1.5% of their respective genomes.

Dr Ren said scientists had assumed that significant conservation would occur at the deeper level of gene regulation as well, that similar genes in humans and mice would be expressed in similar ways.

Using the same high throughput technologies applied in the human ENCODE project, he and his colleagues analyzed 100 different mouse cell types and tissues.

They found that, while much conservation did exist, the expression profiles of some distinct biological pathways in mouse samples diverged considerably from human samples.

Put another way, core genomic programs were largely conserved between the species, but genes and their underlying regulatory programs had changed significantly over time. Each species had evolved to find different ways to do some of the same things.

The findings are not entirely unexpected. Dr Ren said previous studies had documented rapidly evolving transcription factors in a handful of cell types and model organisms, but the ability to more systematically discern how humans and mice differ in genomic function marks an important milestone.

“One benefit is that, while mice have proved to be substantially different than humans in some ways, we now have a better idea of where exactly they are different, where we will need to take into account those differences, perhaps finding or developing a better model, and where the mouse continues to be a very good model indeed,” Dr Ren concluded.

Visit the following links for the mouse ENCODE papers published yesterday in Nature and Science:

A comparative encyclopedia of DNA elements in the mouse genome

Conservation of trans-acting circuitry during mammalian regulatory evolution

Principles of regulatory information conservation between mouse and human

Topologically associating domains are stable units of replication-timing regulation

Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution

Related studies are set to appear in PNAS, Genome Research, Genome Biology, Nature Communications, and Blood.

Lab mice

Credit: Aaron Logan

Scientists have long known that mice are not perfect models for studying conditions in humans, but new research reveals why certain processes and systems in

mice are so different from those in humans.

As part of the mouse ENCODE project, researchers discovered that a significant number of mouse genes do not behave like their human counterparts.

This suggests scientists will need to rethink at least some roles of the lab mouse as a model organism.

“There are a substantial number of mouse genes that are regulated in ways different from similar genes in humans,” said Bing Ren, PhD, of the University of California, San Diego.

“The differences are not random. They are clustered along certain pathways, such as in genes regulating the immune system.”

The findings, part of a series of related papers being published in Nature, Science, and other journals (see below), are derived from the ongoing mouse ENCODE (Encyclopedia of DNA Elements) project.

This multi-institution effort was launched in 2007 to build a comprehensive list of functional elements of the mouse genome. It complements the earlier human ENCODE project, which published its functional catalogue in 2012.

“Both the original human and mouse genome projects gave us the sequence of genetic letters that comprise each organism but no idea how they worked or worked together to create and sustain life,” Dr Ren said.

“The human ENCODE project was designed to answer some of those questions. The mouse ENCODE project is its complement. It’s intended to provide scientists with comprehensive annotation of what mouse genes do, information that may ultimately be used for human therapeutic purposes.”

Only half of human genomic DNA aligns to mouse genomic DNA. But protein-coding genes, which provide the actionable instructions to build a living organism, are more strongly conserved across the two species.

Mice and humans share approximately 70% of the same protein-coding gene sequences, though these genes constitute just 1.5% of their respective genomes.

Dr Ren said scientists had assumed that significant conservation would occur at the deeper level of gene regulation as well, that similar genes in humans and mice would be expressed in similar ways.

Using the same high throughput technologies applied in the human ENCODE project, he and his colleagues analyzed 100 different mouse cell types and tissues.

They found that, while much conservation did exist, the expression profiles of some distinct biological pathways in mouse samples diverged considerably from human samples.

Put another way, core genomic programs were largely conserved between the species, but genes and their underlying regulatory programs had changed significantly over time. Each species had evolved to find different ways to do some of the same things.

The findings are not entirely unexpected. Dr Ren said previous studies had documented rapidly evolving transcription factors in a handful of cell types and model organisms, but the ability to more systematically discern how humans and mice differ in genomic function marks an important milestone.

“One benefit is that, while mice have proved to be substantially different than humans in some ways, we now have a better idea of where exactly they are different, where we will need to take into account those differences, perhaps finding or developing a better model, and where the mouse continues to be a very good model indeed,” Dr Ren concluded.

Visit the following links for the mouse ENCODE papers published yesterday in Nature and Science:

A comparative encyclopedia of DNA elements in the mouse genome

Conservation of trans-acting circuitry during mammalian regulatory evolution

Principles of regulatory information conservation between mouse and human

Topologically associating domains are stable units of replication-timing regulation

Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution

Related studies are set to appear in PNAS, Genome Research, Genome Biology, Nature Communications, and Blood.

Lab mice

Credit: Aaron Logan

Scientists have long known that mice are not perfect models for studying conditions in humans, but new research reveals why certain processes and systems in

mice are so different from those in humans.

As part of the mouse ENCODE project, researchers discovered that a significant number of mouse genes do not behave like their human counterparts.

This suggests scientists will need to rethink at least some roles of the lab mouse as a model organism.

“There are a substantial number of mouse genes that are regulated in ways different from similar genes in humans,” said Bing Ren, PhD, of the University of California, San Diego.

“The differences are not random. They are clustered along certain pathways, such as in genes regulating the immune system.”

The findings, part of a series of related papers being published in Nature, Science, and other journals (see below), are derived from the ongoing mouse ENCODE (Encyclopedia of DNA Elements) project.

This multi-institution effort was launched in 2007 to build a comprehensive list of functional elements of the mouse genome. It complements the earlier human ENCODE project, which published its functional catalogue in 2012.

“Both the original human and mouse genome projects gave us the sequence of genetic letters that comprise each organism but no idea how they worked or worked together to create and sustain life,” Dr Ren said.

“The human ENCODE project was designed to answer some of those questions. The mouse ENCODE project is its complement. It’s intended to provide scientists with comprehensive annotation of what mouse genes do, information that may ultimately be used for human therapeutic purposes.”

Only half of human genomic DNA aligns to mouse genomic DNA. But protein-coding genes, which provide the actionable instructions to build a living organism, are more strongly conserved across the two species.

Mice and humans share approximately 70% of the same protein-coding gene sequences, though these genes constitute just 1.5% of their respective genomes.

Dr Ren said scientists had assumed that significant conservation would occur at the deeper level of gene regulation as well, that similar genes in humans and mice would be expressed in similar ways.

Using the same high throughput technologies applied in the human ENCODE project, he and his colleagues analyzed 100 different mouse cell types and tissues.

They found that, while much conservation did exist, the expression profiles of some distinct biological pathways in mouse samples diverged considerably from human samples.

Put another way, core genomic programs were largely conserved between the species, but genes and their underlying regulatory programs had changed significantly over time. Each species had evolved to find different ways to do some of the same things.

The findings are not entirely unexpected. Dr Ren said previous studies had documented rapidly evolving transcription factors in a handful of cell types and model organisms, but the ability to more systematically discern how humans and mice differ in genomic function marks an important milestone.

“One benefit is that, while mice have proved to be substantially different than humans in some ways, we now have a better idea of where exactly they are different, where we will need to take into account those differences, perhaps finding or developing a better model, and where the mouse continues to be a very good model indeed,” Dr Ren concluded.

Visit the following links for the mouse ENCODE papers published yesterday in Nature and Science:

A comparative encyclopedia of DNA elements in the mouse genome

Conservation of trans-acting circuitry during mammalian regulatory evolution

Principles of regulatory information conservation between mouse and human

Topologically associating domains are stable units of replication-timing regulation

Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution

Related studies are set to appear in PNAS, Genome Research, Genome Biology, Nature Communications, and Blood.

Benzodiazepines are regularly used to treat anxiety, insomnia, and depression. Guidelines advise only short-term benzodiazepine use for elderly patients, but long-term treatment is still common. According to researchers from the University of Montreal in Canada and the University of Bordeaux in France, long-term dosing can do more harm than good for patients at risk for Alzheimer disease. Previous research has established that long-term benzodiazepine use can have deleterious effects on memory and cognition, say the researchers.

Earlier studies could not prove a connection between the drugs and dementia, because they did not have sufficient power, follow-up was too short, or because of other methodologic limitations. To counter those earlier limitations, the researchers designed their study to assess benzodiazepine treatments initiated > 5 years before the diagnosis of Alzheimer disease or dementia, when prescriptions were less likely to be motivated by prodromes.

The researchers used an administrative claims database with a long follow-up period to look at the potential dose-effect relationship. They defined exposure by 3 criteria: “ever use” (≥ 1 claim for a benzodiazepine from 5 to 10 years before the index date); cumulative dose (≤ 3 months, 3 to 6 months, or > 6 months [long-term use]); and drug elimination half-life (short- [< 20 hours] or long-acting benzodiazepines). The researchers matched 1,796 patients with 7,184 controls and followed them for ≥ 6 years before the index date.

The risk of Alzheimer disease, the study revealed, increased by 43% to 51% among people who had used benzodiazepines in the past: 894 (49.8%) people with Alzheimer disease had used benzodiazepines at some point, compared with 2,873 controls (40%). Short-term use did not differ between the 2 groups. Long-term use was more common among people with Alzheimer disease, the researchers found: 32.9% of those with Alzheimer disease compared with 21.8% of those in the control group.

Risk of Alzheimer disease increased when long-acting benzodiazepines were used. Because there is no prevention or cure for Alzheimer disease, the researchers urge focusing on duration of benzodiazepine use and other modifiable risk factors.

Source
Billioti de Gage S, Moride Y, Ducruet T, et al. BMJ. 2014;349:g5205.
doi: 10.1136/bmj.g5205.

Benzodiazepines are regularly used to treat anxiety, insomnia, and depression. Guidelines advise only short-term benzodiazepine use for elderly patients, but long-term treatment is still common. According to researchers from the University of Montreal in Canada and the University of Bordeaux in France, long-term dosing can do more harm than good for patients at risk for Alzheimer disease. Previous research has established that long-term benzodiazepine use can have deleterious effects on memory and cognition, say the researchers.

Earlier studies could not prove a connection between the drugs and dementia, because they did not have sufficient power, follow-up was too short, or because of other methodologic limitations. To counter those earlier limitations, the researchers designed their study to assess benzodiazepine treatments initiated > 5 years before the diagnosis of Alzheimer disease or dementia, when prescriptions were less likely to be motivated by prodromes.

The researchers used an administrative claims database with a long follow-up period to look at the potential dose-effect relationship. They defined exposure by 3 criteria: “ever use” (≥ 1 claim for a benzodiazepine from 5 to 10 years before the index date); cumulative dose (≤ 3 months, 3 to 6 months, or > 6 months [long-term use]); and drug elimination half-life (short- [< 20 hours] or long-acting benzodiazepines). The researchers matched 1,796 patients with 7,184 controls and followed them for ≥ 6 years before the index date.

The risk of Alzheimer disease, the study revealed, increased by 43% to 51% among people who had used benzodiazepines in the past: 894 (49.8%) people with Alzheimer disease had used benzodiazepines at some point, compared with 2,873 controls (40%). Short-term use did not differ between the 2 groups. Long-term use was more common among people with Alzheimer disease, the researchers found: 32.9% of those with Alzheimer disease compared with 21.8% of those in the control group.

Risk of Alzheimer disease increased when long-acting benzodiazepines were used. Because there is no prevention or cure for Alzheimer disease, the researchers urge focusing on duration of benzodiazepine use and other modifiable risk factors.

Source
Billioti de Gage S, Moride Y, Ducruet T, et al. BMJ. 2014;349:g5205.
doi: 10.1136/bmj.g5205.

Benzodiazepines are regularly used to treat anxiety, insomnia, and depression. Guidelines advise only short-term benzodiazepine use for elderly patients, but long-term treatment is still common. According to researchers from the University of Montreal in Canada and the University of Bordeaux in France, long-term dosing can do more harm than good for patients at risk for Alzheimer disease. Previous research has established that long-term benzodiazepine use can have deleterious effects on memory and cognition, say the researchers.

Earlier studies could not prove a connection between the drugs and dementia, because they did not have sufficient power, follow-up was too short, or because of other methodologic limitations. To counter those earlier limitations, the researchers designed their study to assess benzodiazepine treatments initiated > 5 years before the diagnosis of Alzheimer disease or dementia, when prescriptions were less likely to be motivated by prodromes.

The researchers used an administrative claims database with a long follow-up period to look at the potential dose-effect relationship. They defined exposure by 3 criteria: “ever use” (≥ 1 claim for a benzodiazepine from 5 to 10 years before the index date); cumulative dose (≤ 3 months, 3 to 6 months, or > 6 months [long-term use]); and drug elimination half-life (short- [< 20 hours] or long-acting benzodiazepines). The researchers matched 1,796 patients with 7,184 controls and followed them for ≥ 6 years before the index date.

The risk of Alzheimer disease, the study revealed, increased by 43% to 51% among people who had used benzodiazepines in the past: 894 (49.8%) people with Alzheimer disease had used benzodiazepines at some point, compared with 2,873 controls (40%). Short-term use did not differ between the 2 groups. Long-term use was more common among people with Alzheimer disease, the researchers found: 32.9% of those with Alzheimer disease compared with 21.8% of those in the control group.

Risk of Alzheimer disease increased when long-acting benzodiazepines were used. Because there is no prevention or cure for Alzheimer disease, the researchers urge focusing on duration of benzodiazepine use and other modifiable risk factors.

Source
Billioti de Gage S, Moride Y, Ducruet T, et al. BMJ. 2014;349:g5205.
doi: 10.1136/bmj.g5205.

Herman Eisen, MD

Photo courtesy of MIT

Herman Eisen, MD, a respected immunologist, has died at the age of 96.

Over a 70-year career, Dr Eisen contributed a great deal to his own field and other fields of research.

He published work describing affinity maturation, clarified the basis for certain allergic reactions, and provided new insight into multiple myeloma and other cancers.

Dr Eisen was a professor emeritus of biology at the Massachusetts Institute of Technology (MIT) and a founding member of the MIT Center for Cancer Research (now the Koch Institute for Integrative Cancer Research).

He joined MIT in 1973 and retired in 1989, but only in the official sense. As a professor emeritus, he maintained an active lab and continued to research, publish, and advise students and postdocs at MIT until his passing.

Early years

Born in 1918 in Brooklyn, New York, Dr Eisen developed a keen interest in science at an early age, when a high school chemistry class helped frame his perception of the world as a collection of atoms and molecules.

Dr Eisen began premedical studies at New York University (NYU) in 1934, but halfway through his undergraduate career, he developed tuberculosis and left school. Though this kept him out of school for one year, the illness sparked a curiosity about the immune system that would endure for the rest of his life.

Dr Eisen returned to NYU to complete his bachelor’s degree, then enrolled at the university’s medical school. He graduated with an MD in 1943 and then worked as an assistant in the pathology department at the Columbia University College of Physicians and Surgeons before going back to NYU for his residency.

Research interests

Dr Eisen had a strong interest in basic science research, particularly in trying to better understand the body’s immune system. Though career options for physician-scientists had historically been limited, the federal government began to increase its funding of biomedical research through the National Institutes of Health (NIH) following World War II.

Seizing these new opportunities, Dr Eisen became one of the first recipients of an NIH fellowship, which supported his research on sulfonamide-induced antibodies at NYU. These investigations helped him and colleague Fred Karush, PhD, determine the number of antigen-binding sites on antibodies.

After his 2-year NIH fellowship, Dr Eisen worked briefly at the Sloan Kettering Institute before returning once again to NYU as a faculty member.

Inspired by the work of his recently deceased role model, Karl Landsteiner, MD, Dr Eisen studied immune reactions of the skin. In doing so, he clarified the basis for certain allergic responses and showed that only those chemicals capable of forming covalent bonds to skin proteins could cause a characteristic itchy rash.

In 1955, Washington University in St Louis recruited Dr Eisen to join the faculty of its School of Medicine. There, he served as dermatologist-in-chief for 5 years before moving to the Department of Microbiology to serve as chair.

While at Washington University, Dr Eisen published groundbreaking research in which he described affinity maturation: the process by which activated B cells produce antibodies with an increasingly higher affinity for invading pathogens after infection. This process is fundamental to the development of potent immune responses.

“Our understanding of affinity maturation begins with Herman’s papers,” said Arup K. Chakraborty, PhD, director of MIT’s Institute for Medical Engineering and Science.

“Understanding this evolutionary process is critical for vaccine design, and affinity maturation is also mimicked in countless academic laboratories and companies to design antibody-based therapies.”

Cancer research

In response to the National Cancer Act of 1971, MIT tasked Nobel Prize-winning biology professor Salvador Luria, MD, with establishing and leading a new MIT Center for Cancer Research. Wanting to include cancer immunology as a focus of this new center, Dr Luria approached Dr Eisen about joining as a founding faculty member.

Dr Eisen accepted the role and arrived at MIT in 1973 as a professor in the Department of Biology. He brought his immunology expertise to MIT’s new cancer center to study how cancer cells evade the body’s natural immune response.

Much of his work focused on studying myeloma tumors in mice and screening their associated proteins. He found that if he used myeloma proteins from one mouse to immunize other mice from the same strain, they were resistant when challenged with cancer cells.

Dr Eisen and his lab went on to study how CD8 T cells develop into cytotoxic T cells and long-lived memory T cells. Therapeutic vaccines that exploit CD8 responses have not yet been developed for humans.

Dr Eisen was working to understand and overcome the barriers to creating effective CD8 vaccines, and his research on the subject was of particular importance to the advancement of cancer immunology.

“Herman’s lifelong pursuit of science, even to the very last day of his life, has been an inspiration to many of us,” said Jianzhu Chen, PhD, of the Koch Institute. “He was a great human being with a great attitude and a clear mind. He will be missed greatly.”

Other colleagues remember Dr Eisen not only as a respected immunologist, but as a hardworking collaborator and a man of integrity. He continued to be an active scientist and had been working with Dr Chakraborty on a paper until his passing.

“Herman was a giant in the field of immunology, with many seminal discoveries,” Dr Chakraborty said. “He was also the kindest and most generous and moral person I have known. Until the end, he was working on scientific problems with junior colleagues and students who benefited from his wisdom. I am lucky to have worked with this great scientist and wonderful human being.”

Dr Eisen was elected to the American Academy of Arts and Sciences in 1965, the National Academy of Sciences in 1969, and the Institute of Medicine of the National Academies in 1974.

He received numerous other awards and honors throughout his career, including the Behring-Heidelberger Award from the American Association of Immunologists, an Outstanding Investigator Award from the National Cancer Institute, and the Lifetime Service Award from the American Association of Immunologists, of which he served as president from 1968 to 1969.

Dr Eisen passed away on November 2. He is survived by his wife Natalie and their children, Ellen, Jane, Jim, Tom, and Matthew, as well as 12 grandchildren.

Herman Eisen, MD

Photo courtesy of MIT

Herman Eisen, MD, a respected immunologist, has died at the age of 96.

Over a 70-year career, Dr Eisen contributed a great deal to his own field and other fields of research.

He published work describing affinity maturation, clarified the basis for certain allergic reactions, and provided new insight into multiple myeloma and other cancers.

Dr Eisen was a professor emeritus of biology at the Massachusetts Institute of Technology (MIT) and a founding member of the MIT Center for Cancer Research (now the Koch Institute for Integrative Cancer Research).

He joined MIT in 1973 and retired in 1989, but only in the official sense. As a professor emeritus, he maintained an active lab and continued to research, publish, and advise students and postdocs at MIT until his passing.

Early years

Born in 1918 in Brooklyn, New York, Dr Eisen developed a keen interest in science at an early age, when a high school chemistry class helped frame his perception of the world as a collection of atoms and molecules.

Dr Eisen began premedical studies at New York University (NYU) in 1934, but halfway through his undergraduate career, he developed tuberculosis and left school. Though this kept him out of school for one year, the illness sparked a curiosity about the immune system that would endure for the rest of his life.

Dr Eisen returned to NYU to complete his bachelor’s degree, then enrolled at the university’s medical school. He graduated with an MD in 1943 and then worked as an assistant in the pathology department at the Columbia University College of Physicians and Surgeons before going back to NYU for his residency.

Research interests

Dr Eisen had a strong interest in basic science research, particularly in trying to better understand the body’s immune system. Though career options for physician-scientists had historically been limited, the federal government began to increase its funding of biomedical research through the National Institutes of Health (NIH) following World War II.

Seizing these new opportunities, Dr Eisen became one of the first recipients of an NIH fellowship, which supported his research on sulfonamide-induced antibodies at NYU. These investigations helped him and colleague Fred Karush, PhD, determine the number of antigen-binding sites on antibodies.

After his 2-year NIH fellowship, Dr Eisen worked briefly at the Sloan Kettering Institute before returning once again to NYU as a faculty member.

Inspired by the work of his recently deceased role model, Karl Landsteiner, MD, Dr Eisen studied immune reactions of the skin. In doing so, he clarified the basis for certain allergic responses and showed that only those chemicals capable of forming covalent bonds to skin proteins could cause a characteristic itchy rash.

In 1955, Washington University in St Louis recruited Dr Eisen to join the faculty of its School of Medicine. There, he served as dermatologist-in-chief for 5 years before moving to the Department of Microbiology to serve as chair.

While at Washington University, Dr Eisen published groundbreaking research in which he described affinity maturation: the process by which activated B cells produce antibodies with an increasingly higher affinity for invading pathogens after infection. This process is fundamental to the development of potent immune responses.

“Our understanding of affinity maturation begins with Herman’s papers,” said Arup K. Chakraborty, PhD, director of MIT’s Institute for Medical Engineering and Science.

“Understanding this evolutionary process is critical for vaccine design, and affinity maturation is also mimicked in countless academic laboratories and companies to design antibody-based therapies.”

Cancer research

In response to the National Cancer Act of 1971, MIT tasked Nobel Prize-winning biology professor Salvador Luria, MD, with establishing and leading a new MIT Center for Cancer Research. Wanting to include cancer immunology as a focus of this new center, Dr Luria approached Dr Eisen about joining as a founding faculty member.

Dr Eisen accepted the role and arrived at MIT in 1973 as a professor in the Department of Biology. He brought his immunology expertise to MIT’s new cancer center to study how cancer cells evade the body’s natural immune response.

Much of his work focused on studying myeloma tumors in mice and screening their associated proteins. He found that if he used myeloma proteins from one mouse to immunize other mice from the same strain, they were resistant when challenged with cancer cells.

Dr Eisen and his lab went on to study how CD8 T cells develop into cytotoxic T cells and long-lived memory T cells. Therapeutic vaccines that exploit CD8 responses have not yet been developed for humans.

Dr Eisen was working to understand and overcome the barriers to creating effective CD8 vaccines, and his research on the subject was of particular importance to the advancement of cancer immunology.

“Herman’s lifelong pursuit of science, even to the very last day of his life, has been an inspiration to many of us,” said Jianzhu Chen, PhD, of the Koch Institute. “He was a great human being with a great attitude and a clear mind. He will be missed greatly.”

Other colleagues remember Dr Eisen not only as a respected immunologist, but as a hardworking collaborator and a man of integrity. He continued to be an active scientist and had been working with Dr Chakraborty on a paper until his passing.

“Herman was a giant in the field of immunology, with many seminal discoveries,” Dr Chakraborty said. “He was also the kindest and most generous and moral person I have known. Until the end, he was working on scientific problems with junior colleagues and students who benefited from his wisdom. I am lucky to have worked with this great scientist and wonderful human being.”

Dr Eisen was elected to the American Academy of Arts and Sciences in 1965, the National Academy of Sciences in 1969, and the Institute of Medicine of the National Academies in 1974.

He received numerous other awards and honors throughout his career, including the Behring-Heidelberger Award from the American Association of Immunologists, an Outstanding Investigator Award from the National Cancer Institute, and the Lifetime Service Award from the American Association of Immunologists, of which he served as president from 1968 to 1969.

Dr Eisen passed away on November 2. He is survived by his wife Natalie and their children, Ellen, Jane, Jim, Tom, and Matthew, as well as 12 grandchildren.

Herman Eisen, MD

Photo courtesy of MIT

Herman Eisen, MD, a respected immunologist, has died at the age of 96.

Over a 70-year career, Dr Eisen contributed a great deal to his own field and other fields of research.

He published work describing affinity maturation, clarified the basis for certain allergic reactions, and provided new insight into multiple myeloma and other cancers.

Dr Eisen was a professor emeritus of biology at the Massachusetts Institute of Technology (MIT) and a founding member of the MIT Center for Cancer Research (now the Koch Institute for Integrative Cancer Research).

He joined MIT in 1973 and retired in 1989, but only in the official sense. As a professor emeritus, he maintained an active lab and continued to research, publish, and advise students and postdocs at MIT until his passing.

Early years

Born in 1918 in Brooklyn, New York, Dr Eisen developed a keen interest in science at an early age, when a high school chemistry class helped frame his perception of the world as a collection of atoms and molecules.

Dr Eisen began premedical studies at New York University (NYU) in 1934, but halfway through his undergraduate career, he developed tuberculosis and left school. Though this kept him out of school for one year, the illness sparked a curiosity about the immune system that would endure for the rest of his life.

Dr Eisen returned to NYU to complete his bachelor’s degree, then enrolled at the university’s medical school. He graduated with an MD in 1943 and then worked as an assistant in the pathology department at the Columbia University College of Physicians and Surgeons before going back to NYU for his residency.

Research interests

Dr Eisen had a strong interest in basic science research, particularly in trying to better understand the body’s immune system. Though career options for physician-scientists had historically been limited, the federal government began to increase its funding of biomedical research through the National Institutes of Health (NIH) following World War II.

Seizing these new opportunities, Dr Eisen became one of the first recipients of an NIH fellowship, which supported his research on sulfonamide-induced antibodies at NYU. These investigations helped him and colleague Fred Karush, PhD, determine the number of antigen-binding sites on antibodies.

After his 2-year NIH fellowship, Dr Eisen worked briefly at the Sloan Kettering Institute before returning once again to NYU as a faculty member.

Inspired by the work of his recently deceased role model, Karl Landsteiner, MD, Dr Eisen studied immune reactions of the skin. In doing so, he clarified the basis for certain allergic responses and showed that only those chemicals capable of forming covalent bonds to skin proteins could cause a characteristic itchy rash.

In 1955, Washington University in St Louis recruited Dr Eisen to join the faculty of its School of Medicine. There, he served as dermatologist-in-chief for 5 years before moving to the Department of Microbiology to serve as chair.

While at Washington University, Dr Eisen published groundbreaking research in which he described affinity maturation: the process by which activated B cells produce antibodies with an increasingly higher affinity for invading pathogens after infection. This process is fundamental to the development of potent immune responses.

“Our understanding of affinity maturation begins with Herman’s papers,” said Arup K. Chakraborty, PhD, director of MIT’s Institute for Medical Engineering and Science.

“Understanding this evolutionary process is critical for vaccine design, and affinity maturation is also mimicked in countless academic laboratories and companies to design antibody-based therapies.”

Cancer research

In response to the National Cancer Act of 1971, MIT tasked Nobel Prize-winning biology professor Salvador Luria, MD, with establishing and leading a new MIT Center for Cancer Research. Wanting to include cancer immunology as a focus of this new center, Dr Luria approached Dr Eisen about joining as a founding faculty member.

Dr Eisen accepted the role and arrived at MIT in 1973 as a professor in the Department of Biology. He brought his immunology expertise to MIT’s new cancer center to study how cancer cells evade the body’s natural immune response.

Much of his work focused on studying myeloma tumors in mice and screening their associated proteins. He found that if he used myeloma proteins from one mouse to immunize other mice from the same strain, they were resistant when challenged with cancer cells.

Dr Eisen and his lab went on to study how CD8 T cells develop into cytotoxic T cells and long-lived memory T cells. Therapeutic vaccines that exploit CD8 responses have not yet been developed for humans.

Dr Eisen was working to understand and overcome the barriers to creating effective CD8 vaccines, and his research on the subject was of particular importance to the advancement of cancer immunology.

“Herman’s lifelong pursuit of science, even to the very last day of his life, has been an inspiration to many of us,” said Jianzhu Chen, PhD, of the Koch Institute. “He was a great human being with a great attitude and a clear mind. He will be missed greatly.”

Other colleagues remember Dr Eisen not only as a respected immunologist, but as a hardworking collaborator and a man of integrity. He continued to be an active scientist and had been working with Dr Chakraborty on a paper until his passing.

“Herman was a giant in the field of immunology, with many seminal discoveries,” Dr Chakraborty said. “He was also the kindest and most generous and moral person I have known. Until the end, he was working on scientific problems with junior colleagues and students who benefited from his wisdom. I am lucky to have worked with this great scientist and wonderful human being.”

Dr Eisen was elected to the American Academy of Arts and Sciences in 1965, the National Academy of Sciences in 1969, and the Institute of Medicine of the National Academies in 1974.

He received numerous other awards and honors throughout his career, including the Behring-Heidelberger Award from the American Association of Immunologists, an Outstanding Investigator Award from the National Cancer Institute, and the Lifetime Service Award from the American Association of Immunologists, of which he served as president from 1968 to 1969.

Dr Eisen passed away on November 2. He is survived by his wife Natalie and their children, Ellen, Jane, Jim, Tom, and Matthew, as well as 12 grandchildren.

CML cells

Credit: UCSD School of Medicine

By analyzing structural changes that occur during Abl kinase activation, researchers have gained new insight into this process.

The team discovered a mechanism that links the allosteric regulation of the SH2 domain to two critical phosphorylation events.

As allosteric SH2-kinase domain interactions have proven essential for leukemogenesis caused by Bcr-Abl, the researchers believe this finding has implications for treating chronic myeloid leukemia (CML).

Oliver Hantschel, PhD, of the École polytechnique fédérale de Lausanne (EPFL) in Lausanne, Switzerland, and his colleagues described this work in Nature Communications.

The team made small, strategic mutations to Abl kinase that caused its 3D structure to change. Then, they tested each mutant version of the enzyme to see if its function would change.

The researchers built on previous studies showing that Abl kinase is indirectly controlled by the SH2 region. Normally, the SH2 region regulates the activation loop by opening and closing it. But under the Philadelphia chromosome translocation, that regulation is lost.

The team discovered that when the Philadelphia mutation takes effect, the SH2 region changes the Abl activation loop to a fully open conformation. This enables the trans-autophosphorylation of the activation loop and requires prior phosphorylation of the SH2-kinase linker.

This discovery provides the first-ever picture of the molecular events surrounding the hyperactivity of Abl kinase, the researchers said.

They also found that by disrupting the SH2-kinase interaction, it’s possible to modulate the activity of Abl kinase, which could potentially stop the growth of leukemia.

Since the SH2 region is common to other kinases, the researchers think it’s likely the effect could extend to malignancies other than CML as well, particularly those characterized by abnormal kinase activity.

Finally, the team expects this approach could overcome the problem of drug resistance in CML, as it might offer an alternative way to inhibit Abl kinase, and mutations of rapidly growing cancer cells may be less likely to occur.

CML cells

Credit: UCSD School of Medicine

By analyzing structural changes that occur during Abl kinase activation, researchers have gained new insight into this process.

The team discovered a mechanism that links the allosteric regulation of the SH2 domain to two critical phosphorylation events.

As allosteric SH2-kinase domain interactions have proven essential for leukemogenesis caused by Bcr-Abl, the researchers believe this finding has implications for treating chronic myeloid leukemia (CML).

Oliver Hantschel, PhD, of the École polytechnique fédérale de Lausanne (EPFL) in Lausanne, Switzerland, and his colleagues described this work in Nature Communications.

The team made small, strategic mutations to Abl kinase that caused its 3D structure to change. Then, they tested each mutant version of the enzyme to see if its function would change.

The researchers built on previous studies showing that Abl kinase is indirectly controlled by the SH2 region. Normally, the SH2 region regulates the activation loop by opening and closing it. But under the Philadelphia chromosome translocation, that regulation is lost.

The team discovered that when the Philadelphia mutation takes effect, the SH2 region changes the Abl activation loop to a fully open conformation. This enables the trans-autophosphorylation of the activation loop and requires prior phosphorylation of the SH2-kinase linker.

This discovery provides the first-ever picture of the molecular events surrounding the hyperactivity of Abl kinase, the researchers said.

They also found that by disrupting the SH2-kinase interaction, it’s possible to modulate the activity of Abl kinase, which could potentially stop the growth of leukemia.

Since the SH2 region is common to other kinases, the researchers think it’s likely the effect could extend to malignancies other than CML as well, particularly those characterized by abnormal kinase activity.

Finally, the team expects this approach could overcome the problem of drug resistance in CML, as it might offer an alternative way to inhibit Abl kinase, and mutations of rapidly growing cancer cells may be less likely to occur.

CML cells

Credit: UCSD School of Medicine

By analyzing structural changes that occur during Abl kinase activation, researchers have gained new insight into this process.

The team discovered a mechanism that links the allosteric regulation of the SH2 domain to two critical phosphorylation events.

As allosteric SH2-kinase domain interactions have proven essential for leukemogenesis caused by Bcr-Abl, the researchers believe this finding has implications for treating chronic myeloid leukemia (CML).

Oliver Hantschel, PhD, of the École polytechnique fédérale de Lausanne (EPFL) in Lausanne, Switzerland, and his colleagues described this work in Nature Communications.

The team made small, strategic mutations to Abl kinase that caused its 3D structure to change. Then, they tested each mutant version of the enzyme to see if its function would change.

The researchers built on previous studies showing that Abl kinase is indirectly controlled by the SH2 region. Normally, the SH2 region regulates the activation loop by opening and closing it. But under the Philadelphia chromosome translocation, that regulation is lost.

The team discovered that when the Philadelphia mutation takes effect, the SH2 region changes the Abl activation loop to a fully open conformation. This enables the trans-autophosphorylation of the activation loop and requires prior phosphorylation of the SH2-kinase linker.

This discovery provides the first-ever picture of the molecular events surrounding the hyperactivity of Abl kinase, the researchers said.

They also found that by disrupting the SH2-kinase interaction, it’s possible to modulate the activity of Abl kinase, which could potentially stop the growth of leukemia.

Since the SH2 region is common to other kinases, the researchers think it’s likely the effect could extend to malignancies other than CML as well, particularly those characterized by abnormal kinase activity.

Finally, the team expects this approach could overcome the problem of drug resistance in CML, as it might offer an alternative way to inhibit Abl kinase, and mutations of rapidly growing cancer cells may be less likely to occur.

Midfoot (Lisfranc) joint injuries are uncommon in the general population, with a reported incidence ranging from 1 per 50,000 to 1 per 60,000 per year.^1,2 The majority of these midfoot injuries result from high-velocity direct trauma involving severe disruption of the tarsometatarsal joint.^1-6 Most of the literature on Lisfranc injuries are based on cohorts that include trauma patients. On the other hand, low-velocity indirect injuries of the tarsometatarsal joint have also been associated with midfoot or Lisfranc sprains.⁷ These injuries are even less extensively studied in athletes, who may sustain them from torsion or the shoe–surface interface.⁸

Foot and ankle injuries are among the most common injuries in athletes and represent 16% to 22% of all sports injuries.⁹ Although midfoot sprains are not common in the general population, sporting activities appear to result in a higher rate of midfoot injury, especially in elite athletes. In fact, midfoot sprains comprise the second most common athlete injury to the foot, after metatarsophalangeal joint injuries.¹⁰ Football players are especially prone to midfoot sprains; incidence is 4% per year, with offensive linemen sustaining 29.2% of midfoot sprains.¹⁰ The most common mechanism of injury is an axial longitudinal force while the foot is plantarflexed and slightly rotated.^11,12

There is a paucity of literature detailing the impact of midfoot injuries on football players.^8,10,13 A study of 23 collegiate football players found that they may have initially underwent a long period of acute disability but had very minor long-term complaints resulting in residual functional disability.¹⁰ However, there are no case series detailing the impact of midfoot sprains on professional football players for whom delayed return to sport can potentially have a devastating impact on a career in terms of both acute- and long-term disability.

We conducted a study to further define the mechanism of injury, diagnosis, treatment, and outcomes among National Football League (NFL) players with midfoot sprains. In addition, we aimed to provide a qualitative analysis of diagnostic and treatment algorithms being used by NFL team physicians in their management of midfoot sprains in these high-level contact athletes.

Materials and Methods

We evaluated midfoot sprains in NFL players in 2 specific phases. In phase 1, we retrospectively reviewed prospectively collected data involving midfoot sprains in professional players from a single NFL team over a 15-year period. In phase 2, we collated diagnostic and treatment algorithms for midfoot sprains among all 32 NFL team physicians by means of a structured questionnaire. Institutional review board approval was obtained for this study at the investigators’ institution.

In phase 1, a NFL team injury database was reviewed for midfoot sprains that had been prospectively entered by a team-certified athletic trainer after consultation with the head orthopedic team physician. All injury and diagnostic modalities and treatments were then analyzed. These included player position, foot and ankle protective gear (none, tape, brace, or unknown), playing surface (grass, AstroTurf, FieldTurf, or unknown), field condition (normal, wet, hard, or unknown), onset of injury (acute, chronic, or unknown), place of injury (game or practice), time of injury in game or practice (first quarter, second quarter, third quarter, fourth quarter, or unknown), type of play (collision, tackled, tackling, blocked, blocking, running/cutting, kicking, or unknown), and mechanism of injury (direct, torsion, shearing, or unknown).

Once the diagnosis was confirmed by physical examination and radiographic findings, midfoot sprain treatment was initiated based on the following algorithm protocols. Nondisplaced sprains were treated with a period of immobilization in a cam walker with progression to weight-bearing as tolerated (grade 1). Once asymptomatic, rehabilitation was initiated, including range of motion, strengthening, and proprioception, and gradual return to play as tolerated. Injuries with subtle diastasis (2-5 mm) were typically treated with nonoperative management in the same manner as the nondisplaced sprain protocol (grade 2); however, signs of gross instability indicated the potential requirement for surgical management. Some of these injuries underwent stress-testing to determine if there was gross instability. If the injury had subtle diastasis with instability or frank (>5 mm) displacement (grade 3), then surgical management was performed with closed versus open reduction and internal fixation (ORIF). The postoperative course included no weight-bearing for 4 to 6 weeks followed by partial weight-bearing for an additional 4 to 6 weeks. After approximately 8 to 12 postoperative weeks, screw removal was performed followed by progression to full weight-bearing and a comprehensive rehabilitation program, including range of motion, strengthening, proprioception, and gradual return to play. Return to play was allowed when the athlete was asymptomatic and had normal range of motion and strength. Time lost from participation was then recorded based on the dates of injury and return to play.

To further elucidate long-term postinjury playing status, we then gathered information from the www.NFL.com historical and current player databases as previously described by Shah and colleagues.¹⁴ From this website, we documented the number of regular-season and postseason games as well as the number of seasons before and after the injury. To be included in the series, the athlete had to have been on the active roster for an NFL franchise at the time of injury. Successful return to play was defined as actual return to play in regular season or postseason NFL games after the midfoot sprain.

In phase 2, a structured electronic questionnaire was sent to all 32 NFL team physicians. The questionnaire was compiled to gather information relating to current diagnostic, treatment, and outcome algorithms in the management of midfoot sprains involving professional football players. Each questionnaire was sent by e-mail to all survey participants and included an embedded link to a secure online survey resource (REDCap Survey Software Version 1.3.9; Vanderbilt University, Nashville, Tennessee). Once the electronic questionnaire was completed by each NFL team physician, results were exported in spreadsheet format for descriptive data analysis.

The retrospective case series and NFL team physician survey data were then analyzed. A descriptive analysis was performed for all variables, including means and minimum–maximum range for quantitative variables as well as frequencies and percentages for qualitative variables. Depending on injury severity, an independent-sample t test with corresponding P values was also calculated for time lost from participation.

Results

The retrospective review of the prospectively collected NFL injury database revealed there were 15 midfoot sprains during the study period. A statistical and descriptive analysis was performed for all study parameters, including player, field, injury, and outcome-specific data. For player, field, and injury-specific data, the results are summarized in the Table.

All grade 1 midfoot sprains (7 nondisplaced) and grade 2 midfoot sprains (5 with subtle diastasis and no instability) were treated with nonoperative management. The 12 players were allowed to return to play without the need for subsequent surgery within the same season. In the evaluation of return to play, based on the severity of the midfoot sprain, there was a statistically significant (P = .047) difference in mean (SD) time lost from participation between the grade 1 sprain group, 3.1 (1.9) days, and the grade 2 sprain group, 36 (26.1) days. Overall, nonoperative treatment of either grade 1 or grade 2 midfoot sprains resulted in a mean of 11.7 days of time lost from participation. In 1 patient with a grade 2 midfoot sprain, the injury occurred toward the end of the season, and the patient was not able to return to play during the remaining 42 days of the season. However, this patient returned to play the next season and had no residual problems.

Three grade 3 injuries (midfoot sprains with frank displacement) required surgical management with ORIF. One patient returned to play the same season, in 73 days; however, the other 2 patients had injuries toward the end of the season (29 and 77 days remaining) and were not able to return to play the same season. However, both these patients returned to play the next season and had no persistent problems. In terms of complications within the same season, there were no recurrent injuries reported after successful return to play.

When evaluating long-term postinjury playing status, we found that 11 (92%) of the 12 NFL players who had nonoperative treatment successfully returned to play. The only player who did not return to an NFL regular season or postseason game was an active-roster NFL player who never actually played in an NFL game before or after his midfoot sprain injury. Our series of NFL players played on average 1.9 years (range, 0-7 years) before the midfoot injury and 5.5 years (range, 0-14 years) after the midfoot injury. In terms of NFL regular-season and postseason games played, our cohort of NFL players played on average 24.0 games (range, 0-80 games) before the midfoot injury and 77.7 games (range, 0-226 games) after the midfoot injury. In fact, 10 of the 12 NFL players (83%) who had nonoperative treatment played more games and seasons after their midfoot injury.

The surveys from phase 2 were completed by all 32 NFL team physicians. When evaluating the severity of midfoot sprains, 63% of the NFL team physicians perform stress-view radiographs. To ascertain NFL team physicians’ management decisions, we evaluated midfoot sprain results according to injury severity, including amount of diastasis.

When managing midfoot sprains with no diastasis, 94% of the team physicians use immobilization, including 27 with a cam walker and 2 with a cast; however, 2 physicians (6%) use only ankle taping or an Ace bandage. Initial weight-bearing status varies among the NFL team physicians, but most (78%) choose to protect the player, including 17 non-weight-bearing, 8 partial weight-bearing, and 7 weight-bearing as tolerated. Most physicians ideally progress players to full weight-bearing by 3 weeks (12% immediately, 12% by week 1, 41% by week 2, 16% by week 3, and 19% from 4-6 weeks).

In the management of midfoot sprains with subtle diastasis, there is variation in treatment modes among the NFL team physicians, with 53% using nonoperative management (34% cam walker, 19% cast) and 47% suggesting operative management. Regardless of treatment, most physicians (97%) maintain initial non-weight-bearing restrictions. In fact, only 1 physician first recommended partial weight-bearing, which corresponded to initial treatment in a cam walker.

In terms of midfoot sprains with frank diastasis, 94% of the NFL team physicians indicated surgical management is warranted, with only 2 physicians (6%) recommending initial nonoperative management with a cam walker. Regardless of treatment, all the physicians (100%) implemented initial non-weight-bearing restrictions. Once surgical treatment was recommended, the preferred fixation method was ORIF using screws (94%) as opposed to closed reduction and internal fixation with percutaneous Kirschner wires (6%). Most of the physicians (59%) do not allow return to play until midfoot hardware is removed; however, 38% allow full participation with contact, and 3% allow partial participation with no contact. Removal of midfoot fixation is an important factor for most of the physicians before considering return to play, and 69% recommend hardware removal after 11 weeks. However, the specific timeline for hardware removal varied among these physicians, with 28% opting for removal at 11 to 12 weeks, 16% at 13 to 14 weeks, 12.5% at 7 to 8 weeks, 12.5% at 15 to 16 weeks, 12.5% at more than 16 weeks, 12.5% never, and 6% at 9 to 10 weeks.

The midfoot sprain treatment protocol (nonoperative vs operative management) based on injury severity was an important factor in considering return-to-play guidelines. When evaluating time lost from participation because of midfoot sprains, most of the NFL team physicians anticipated a period of 5 to 8 weeks when considering nonoperative management (56%) and more than 17 weeks after operative management (53%). In evaluating nonoperative management protocols, return-to-play guidelines were relatively expeditious, with 56% of the physicians estimating from 5 to 8 weeks, 22% from 1 to 4 weeks, 13% from 9 to 12 weeks, 6% from 13 to 16 weeks, and 3% longer than 20 weeks. In comparison to nonoperative management, return-to-play guidelines for operative management were prolonged, with 53% of the physicians estimating more than 20 weeks, 25% from 17 to 20 weeks, 13% from 13 to 16 weeks, and 9% from 9 to 12 weeks.

Discussion

Lisfranc and midfoot injuries remain a controversial topic in sports medicine. Several authors have argued that anatomical reduction of the tarsometatarsal joint in the setting of a Lisfranc injury yields optimal outcomes.^15,16 Some studies have also suggested that purely ligamentous Lisfranc injuries may be more of a problem than bony injuries, which may have the benefit of osseous healing.^15,17 Anatomical reduction can minimize the potential for arch collapse by maintaining the normal tarsometatarsal relationship. However, there are no long-term data to determine how midfoot arthrosis is affected by ORIF, which typically involves hardware traversing joints. Some have even argued that primary tarsometatarsal arthrodesis should be the treatment of choice, as the midfoot has limited native motion, and successful arthrodesis eliminates the potential for midfoot arthrosis.^17,18 However, we are unaware of any studies that have routinely performed arthrodesis in an athletic population.

The majority of studies on midfoot injuries have evaluated individuals involved in traumatic accidents, most commonly motor vehicle collisions. The present study suggests there may be a subset of injuries in athletes that have yet to be adequately studied. Anecdotally, the NFL team physicians surveyed in our study suggested that midfoot sprains with no or subtle displacement may be treated with nonoperative measures while yielding satisfactory clinical outcomes. These results have been quantified in return-to-play status. Our subset of athletes from an NFL team corroborates these findings, even though the series was small (15 patients). Our survey results also suggest there is considerable variation in the “optimal” management plan among the physicians treating these elite athletes. Most would agree that the nondisplaced injuries can be managed conservatively and that the severely displaced injuries should be managed operatively, but the natural history of those injuries with subtle diastasis remains unclear. When operative intervention is implemented, hardware removal versus retention must also be considered when allowing for return to play. Although one would assume that motion-related hardware failure would be possible at the tarsometatarsal joints, this concept has yet to be clearly defined in the literature.

The present study also demonstrates that most athletes with these midfoot injuries can return to play at the elite NFL level, as evidenced by their short- and long-term return to play. However, it was not possible to differentiate the specific return-to-play level related to preinjury performance level. Furthermore, this relatively short-term NFL career follow-up study was not able to elucidate the long-term consequences of these injuries. In fact, arch collapse and acquired flatfoot deformity could eventually result from this injury, and long-term outcomes would be of particular interest in patients who have subtle diastasis and who are treated nonoperatively.

Although previous studies have supported operative management for Lisfranc injuries involving subtle diastasis, more than half of the NFL team physicians surveyed in this study use nonoperative treatment for these injuries.¹⁹ Future studies should evaluate stress-imaging to define the effect of stability or latent diastasis on long-term outcomes. Nonetheless, the present study demonstrates that a large cohort of NFL team physicians supports nonoperative management for these Lisfranc injuries with subtle diastasis, even in elite athletes. Additional prospective studies are needed to provide a more rigorous injury evaluation and closer follow-up, including subjective and objective outcomes, to further define the indications for management options for midfoot sprains in this population of contact athletes.

Midfoot (Lisfranc) joint injuries are uncommon in the general population, with a reported incidence ranging from 1 per 50,000 to 1 per 60,000 per year.^1,2 The majority of these midfoot injuries result from high-velocity direct trauma involving severe disruption of the tarsometatarsal joint.^1-6 Most of the literature on Lisfranc injuries are based on cohorts that include trauma patients. On the other hand, low-velocity indirect injuries of the tarsometatarsal joint have also been associated with midfoot or Lisfranc sprains.⁷ These injuries are even less extensively studied in athletes, who may sustain them from torsion or the shoe–surface interface.⁸

Foot and ankle injuries are among the most common injuries in athletes and represent 16% to 22% of all sports injuries.⁹ Although midfoot sprains are not common in the general population, sporting activities appear to result in a higher rate of midfoot injury, especially in elite athletes. In fact, midfoot sprains comprise the second most common athlete injury to the foot, after metatarsophalangeal joint injuries.¹⁰ Football players are especially prone to midfoot sprains; incidence is 4% per year, with offensive linemen sustaining 29.2% of midfoot sprains.¹⁰ The most common mechanism of injury is an axial longitudinal force while the foot is plantarflexed and slightly rotated.^11,12

There is a paucity of literature detailing the impact of midfoot injuries on football players.^8,10,13 A study of 23 collegiate football players found that they may have initially underwent a long period of acute disability but had very minor long-term complaints resulting in residual functional disability.¹⁰ However, there are no case series detailing the impact of midfoot sprains on professional football players for whom delayed return to sport can potentially have a devastating impact on a career in terms of both acute- and long-term disability.

We conducted a study to further define the mechanism of injury, diagnosis, treatment, and outcomes among National Football League (NFL) players with midfoot sprains. In addition, we aimed to provide a qualitative analysis of diagnostic and treatment algorithms being used by NFL team physicians in their management of midfoot sprains in these high-level contact athletes.

Materials and Methods

We evaluated midfoot sprains in NFL players in 2 specific phases. In phase 1, we retrospectively reviewed prospectively collected data involving midfoot sprains in professional players from a single NFL team over a 15-year period. In phase 2, we collated diagnostic and treatment algorithms for midfoot sprains among all 32 NFL team physicians by means of a structured questionnaire. Institutional review board approval was obtained for this study at the investigators’ institution.

In phase 1, a NFL team injury database was reviewed for midfoot sprains that had been prospectively entered by a team-certified athletic trainer after consultation with the head orthopedic team physician. All injury and diagnostic modalities and treatments were then analyzed. These included player position, foot and ankle protective gear (none, tape, brace, or unknown), playing surface (grass, AstroTurf, FieldTurf, or unknown), field condition (normal, wet, hard, or unknown), onset of injury (acute, chronic, or unknown), place of injury (game or practice), time of injury in game or practice (first quarter, second quarter, third quarter, fourth quarter, or unknown), type of play (collision, tackled, tackling, blocked, blocking, running/cutting, kicking, or unknown), and mechanism of injury (direct, torsion, shearing, or unknown).

Once the diagnosis was confirmed by physical examination and radiographic findings, midfoot sprain treatment was initiated based on the following algorithm protocols. Nondisplaced sprains were treated with a period of immobilization in a cam walker with progression to weight-bearing as tolerated (grade 1). Once asymptomatic, rehabilitation was initiated, including range of motion, strengthening, and proprioception, and gradual return to play as tolerated. Injuries with subtle diastasis (2-5 mm) were typically treated with nonoperative management in the same manner as the nondisplaced sprain protocol (grade 2); however, signs of gross instability indicated the potential requirement for surgical management. Some of these injuries underwent stress-testing to determine if there was gross instability. If the injury had subtle diastasis with instability or frank (>5 mm) displacement (grade 3), then surgical management was performed with closed versus open reduction and internal fixation (ORIF). The postoperative course included no weight-bearing for 4 to 6 weeks followed by partial weight-bearing for an additional 4 to 6 weeks. After approximately 8 to 12 postoperative weeks, screw removal was performed followed by progression to full weight-bearing and a comprehensive rehabilitation program, including range of motion, strengthening, proprioception, and gradual return to play. Return to play was allowed when the athlete was asymptomatic and had normal range of motion and strength. Time lost from participation was then recorded based on the dates of injury and return to play.

To further elucidate long-term postinjury playing status, we then gathered information from the www.NFL.com historical and current player databases as previously described by Shah and colleagues.¹⁴ From this website, we documented the number of regular-season and postseason games as well as the number of seasons before and after the injury. To be included in the series, the athlete had to have been on the active roster for an NFL franchise at the time of injury. Successful return to play was defined as actual return to play in regular season or postseason NFL games after the midfoot sprain.

In phase 2, a structured electronic questionnaire was sent to all 32 NFL team physicians. The questionnaire was compiled to gather information relating to current diagnostic, treatment, and outcome algorithms in the management of midfoot sprains involving professional football players. Each questionnaire was sent by e-mail to all survey participants and included an embedded link to a secure online survey resource (REDCap Survey Software Version 1.3.9; Vanderbilt University, Nashville, Tennessee). Once the electronic questionnaire was completed by each NFL team physician, results were exported in spreadsheet format for descriptive data analysis.

The retrospective case series and NFL team physician survey data were then analyzed. A descriptive analysis was performed for all variables, including means and minimum–maximum range for quantitative variables as well as frequencies and percentages for qualitative variables. Depending on injury severity, an independent-sample t test with corresponding P values was also calculated for time lost from participation.

Results

The retrospective review of the prospectively collected NFL injury database revealed there were 15 midfoot sprains during the study period. A statistical and descriptive analysis was performed for all study parameters, including player, field, injury, and outcome-specific data. For player, field, and injury-specific data, the results are summarized in the Table.

All grade 1 midfoot sprains (7 nondisplaced) and grade 2 midfoot sprains (5 with subtle diastasis and no instability) were treated with nonoperative management. The 12 players were allowed to return to play without the need for subsequent surgery within the same season. In the evaluation of return to play, based on the severity of the midfoot sprain, there was a statistically significant (P = .047) difference in mean (SD) time lost from participation between the grade 1 sprain group, 3.1 (1.9) days, and the grade 2 sprain group, 36 (26.1) days. Overall, nonoperative treatment of either grade 1 or grade 2 midfoot sprains resulted in a mean of 11.7 days of time lost from participation. In 1 patient with a grade 2 midfoot sprain, the injury occurred toward the end of the season, and the patient was not able to return to play during the remaining 42 days of the season. However, this patient returned to play the next season and had no residual problems.

Three grade 3 injuries (midfoot sprains with frank displacement) required surgical management with ORIF. One patient returned to play the same season, in 73 days; however, the other 2 patients had injuries toward the end of the season (29 and 77 days remaining) and were not able to return to play the same season. However, both these patients returned to play the next season and had no persistent problems. In terms of complications within the same season, there were no recurrent injuries reported after successful return to play.

When evaluating long-term postinjury playing status, we found that 11 (92%) of the 12 NFL players who had nonoperative treatment successfully returned to play. The only player who did not return to an NFL regular season or postseason game was an active-roster NFL player who never actually played in an NFL game before or after his midfoot sprain injury. Our series of NFL players played on average 1.9 years (range, 0-7 years) before the midfoot injury and 5.5 years (range, 0-14 years) after the midfoot injury. In terms of NFL regular-season and postseason games played, our cohort of NFL players played on average 24.0 games (range, 0-80 games) before the midfoot injury and 77.7 games (range, 0-226 games) after the midfoot injury. In fact, 10 of the 12 NFL players (83%) who had nonoperative treatment played more games and seasons after their midfoot injury.

The surveys from phase 2 were completed by all 32 NFL team physicians. When evaluating the severity of midfoot sprains, 63% of the NFL team physicians perform stress-view radiographs. To ascertain NFL team physicians’ management decisions, we evaluated midfoot sprain results according to injury severity, including amount of diastasis.

When managing midfoot sprains with no diastasis, 94% of the team physicians use immobilization, including 27 with a cam walker and 2 with a cast; however, 2 physicians (6%) use only ankle taping or an Ace bandage. Initial weight-bearing status varies among the NFL team physicians, but most (78%) choose to protect the player, including 17 non-weight-bearing, 8 partial weight-bearing, and 7 weight-bearing as tolerated. Most physicians ideally progress players to full weight-bearing by 3 weeks (12% immediately, 12% by week 1, 41% by week 2, 16% by week 3, and 19% from 4-6 weeks).

In the management of midfoot sprains with subtle diastasis, there is variation in treatment modes among the NFL team physicians, with 53% using nonoperative management (34% cam walker, 19% cast) and 47% suggesting operative management. Regardless of treatment, most physicians (97%) maintain initial non-weight-bearing restrictions. In fact, only 1 physician first recommended partial weight-bearing, which corresponded to initial treatment in a cam walker.

In terms of midfoot sprains with frank diastasis, 94% of the NFL team physicians indicated surgical management is warranted, with only 2 physicians (6%) recommending initial nonoperative management with a cam walker. Regardless of treatment, all the physicians (100%) implemented initial non-weight-bearing restrictions. Once surgical treatment was recommended, the preferred fixation method was ORIF using screws (94%) as opposed to closed reduction and internal fixation with percutaneous Kirschner wires (6%). Most of the physicians (59%) do not allow return to play until midfoot hardware is removed; however, 38% allow full participation with contact, and 3% allow partial participation with no contact. Removal of midfoot fixation is an important factor for most of the physicians before considering return to play, and 69% recommend hardware removal after 11 weeks. However, the specific timeline for hardware removal varied among these physicians, with 28% opting for removal at 11 to 12 weeks, 16% at 13 to 14 weeks, 12.5% at 7 to 8 weeks, 12.5% at 15 to 16 weeks, 12.5% at more than 16 weeks, 12.5% never, and 6% at 9 to 10 weeks.

The midfoot sprain treatment protocol (nonoperative vs operative management) based on injury severity was an important factor in considering return-to-play guidelines. When evaluating time lost from participation because of midfoot sprains, most of the NFL team physicians anticipated a period of 5 to 8 weeks when considering nonoperative management (56%) and more than 17 weeks after operative management (53%). In evaluating nonoperative management protocols, return-to-play guidelines were relatively expeditious, with 56% of the physicians estimating from 5 to 8 weeks, 22% from 1 to 4 weeks, 13% from 9 to 12 weeks, 6% from 13 to 16 weeks, and 3% longer than 20 weeks. In comparison to nonoperative management, return-to-play guidelines for operative management were prolonged, with 53% of the physicians estimating more than 20 weeks, 25% from 17 to 20 weeks, 13% from 13 to 16 weeks, and 9% from 9 to 12 weeks.

Discussion

Lisfranc and midfoot injuries remain a controversial topic in sports medicine. Several authors have argued that anatomical reduction of the tarsometatarsal joint in the setting of a Lisfranc injury yields optimal outcomes.^15,16 Some studies have also suggested that purely ligamentous Lisfranc injuries may be more of a problem than bony injuries, which may have the benefit of osseous healing.^15,17 Anatomical reduction can minimize the potential for arch collapse by maintaining the normal tarsometatarsal relationship. However, there are no long-term data to determine how midfoot arthrosis is affected by ORIF, which typically involves hardware traversing joints. Some have even argued that primary tarsometatarsal arthrodesis should be the treatment of choice, as the midfoot has limited native motion, and successful arthrodesis eliminates the potential for midfoot arthrosis.^17,18 However, we are unaware of any studies that have routinely performed arthrodesis in an athletic population.

The majority of studies on midfoot injuries have evaluated individuals involved in traumatic accidents, most commonly motor vehicle collisions. The present study suggests there may be a subset of injuries in athletes that have yet to be adequately studied. Anecdotally, the NFL team physicians surveyed in our study suggested that midfoot sprains with no or subtle displacement may be treated with nonoperative measures while yielding satisfactory clinical outcomes. These results have been quantified in return-to-play status. Our subset of athletes from an NFL team corroborates these findings, even though the series was small (15 patients). Our survey results also suggest there is considerable variation in the “optimal” management plan among the physicians treating these elite athletes. Most would agree that the nondisplaced injuries can be managed conservatively and that the severely displaced injuries should be managed operatively, but the natural history of those injuries with subtle diastasis remains unclear. When operative intervention is implemented, hardware removal versus retention must also be considered when allowing for return to play. Although one would assume that motion-related hardware failure would be possible at the tarsometatarsal joints, this concept has yet to be clearly defined in the literature.

The present study also demonstrates that most athletes with these midfoot injuries can return to play at the elite NFL level, as evidenced by their short- and long-term return to play. However, it was not possible to differentiate the specific return-to-play level related to preinjury performance level. Furthermore, this relatively short-term NFL career follow-up study was not able to elucidate the long-term consequences of these injuries. In fact, arch collapse and acquired flatfoot deformity could eventually result from this injury, and long-term outcomes would be of particular interest in patients who have subtle diastasis and who are treated nonoperatively.

Although previous studies have supported operative management for Lisfranc injuries involving subtle diastasis, more than half of the NFL team physicians surveyed in this study use nonoperative treatment for these injuries.¹⁹ Future studies should evaluate stress-imaging to define the effect of stability or latent diastasis on long-term outcomes. Nonetheless, the present study demonstrates that a large cohort of NFL team physicians supports nonoperative management for these Lisfranc injuries with subtle diastasis, even in elite athletes. Additional prospective studies are needed to provide a more rigorous injury evaluation and closer follow-up, including subjective and objective outcomes, to further define the indications for management options for midfoot sprains in this population of contact athletes.

Midfoot (Lisfranc) joint injuries are uncommon in the general population, with a reported incidence ranging from 1 per 50,000 to 1 per 60,000 per year.^1,2 The majority of these midfoot injuries result from high-velocity direct trauma involving severe disruption of the tarsometatarsal joint.^1-6 Most of the literature on Lisfranc injuries are based on cohorts that include trauma patients. On the other hand, low-velocity indirect injuries of the tarsometatarsal joint have also been associated with midfoot or Lisfranc sprains.⁷ These injuries are even less extensively studied in athletes, who may sustain them from torsion or the shoe–surface interface.⁸

Foot and ankle injuries are among the most common injuries in athletes and represent 16% to 22% of all sports injuries.⁹ Although midfoot sprains are not common in the general population, sporting activities appear to result in a higher rate of midfoot injury, especially in elite athletes. In fact, midfoot sprains comprise the second most common athlete injury to the foot, after metatarsophalangeal joint injuries.¹⁰ Football players are especially prone to midfoot sprains; incidence is 4% per year, with offensive linemen sustaining 29.2% of midfoot sprains.¹⁰ The most common mechanism of injury is an axial longitudinal force while the foot is plantarflexed and slightly rotated.^11,12

There is a paucity of literature detailing the impact of midfoot injuries on football players.^8,10,13 A study of 23 collegiate football players found that they may have initially underwent a long period of acute disability but had very minor long-term complaints resulting in residual functional disability.¹⁰ However, there are no case series detailing the impact of midfoot sprains on professional football players for whom delayed return to sport can potentially have a devastating impact on a career in terms of both acute- and long-term disability.

We conducted a study to further define the mechanism of injury, diagnosis, treatment, and outcomes among National Football League (NFL) players with midfoot sprains. In addition, we aimed to provide a qualitative analysis of diagnostic and treatment algorithms being used by NFL team physicians in their management of midfoot sprains in these high-level contact athletes.

Materials and Methods

We evaluated midfoot sprains in NFL players in 2 specific phases. In phase 1, we retrospectively reviewed prospectively collected data involving midfoot sprains in professional players from a single NFL team over a 15-year period. In phase 2, we collated diagnostic and treatment algorithms for midfoot sprains among all 32 NFL team physicians by means of a structured questionnaire. Institutional review board approval was obtained for this study at the investigators’ institution.

In phase 1, a NFL team injury database was reviewed for midfoot sprains that had been prospectively entered by a team-certified athletic trainer after consultation with the head orthopedic team physician. All injury and diagnostic modalities and treatments were then analyzed. These included player position, foot and ankle protective gear (none, tape, brace, or unknown), playing surface (grass, AstroTurf, FieldTurf, or unknown), field condition (normal, wet, hard, or unknown), onset of injury (acute, chronic, or unknown), place of injury (game or practice), time of injury in game or practice (first quarter, second quarter, third quarter, fourth quarter, or unknown), type of play (collision, tackled, tackling, blocked, blocking, running/cutting, kicking, or unknown), and mechanism of injury (direct, torsion, shearing, or unknown).

Once the diagnosis was confirmed by physical examination and radiographic findings, midfoot sprain treatment was initiated based on the following algorithm protocols. Nondisplaced sprains were treated with a period of immobilization in a cam walker with progression to weight-bearing as tolerated (grade 1). Once asymptomatic, rehabilitation was initiated, including range of motion, strengthening, and proprioception, and gradual return to play as tolerated. Injuries with subtle diastasis (2-5 mm) were typically treated with nonoperative management in the same manner as the nondisplaced sprain protocol (grade 2); however, signs of gross instability indicated the potential requirement for surgical management. Some of these injuries underwent stress-testing to determine if there was gross instability. If the injury had subtle diastasis with instability or frank (>5 mm) displacement (grade 3), then surgical management was performed with closed versus open reduction and internal fixation (ORIF). The postoperative course included no weight-bearing for 4 to 6 weeks followed by partial weight-bearing for an additional 4 to 6 weeks. After approximately 8 to 12 postoperative weeks, screw removal was performed followed by progression to full weight-bearing and a comprehensive rehabilitation program, including range of motion, strengthening, proprioception, and gradual return to play. Return to play was allowed when the athlete was asymptomatic and had normal range of motion and strength. Time lost from participation was then recorded based on the dates of injury and return to play.

To further elucidate long-term postinjury playing status, we then gathered information from the www.NFL.com historical and current player databases as previously described by Shah and colleagues.¹⁴ From this website, we documented the number of regular-season and postseason games as well as the number of seasons before and after the injury. To be included in the series, the athlete had to have been on the active roster for an NFL franchise at the time of injury. Successful return to play was defined as actual return to play in regular season or postseason NFL games after the midfoot sprain.

In phase 2, a structured electronic questionnaire was sent to all 32 NFL team physicians. The questionnaire was compiled to gather information relating to current diagnostic, treatment, and outcome algorithms in the management of midfoot sprains involving professional football players. Each questionnaire was sent by e-mail to all survey participants and included an embedded link to a secure online survey resource (REDCap Survey Software Version 1.3.9; Vanderbilt University, Nashville, Tennessee). Once the electronic questionnaire was completed by each NFL team physician, results were exported in spreadsheet format for descriptive data analysis.

The retrospective case series and NFL team physician survey data were then analyzed. A descriptive analysis was performed for all variables, including means and minimum–maximum range for quantitative variables as well as frequencies and percentages for qualitative variables. Depending on injury severity, an independent-sample t test with corresponding P values was also calculated for time lost from participation.

Results

The retrospective review of the prospectively collected NFL injury database revealed there were 15 midfoot sprains during the study period. A statistical and descriptive analysis was performed for all study parameters, including player, field, injury, and outcome-specific data. For player, field, and injury-specific data, the results are summarized in the Table.

All grade 1 midfoot sprains (7 nondisplaced) and grade 2 midfoot sprains (5 with subtle diastasis and no instability) were treated with nonoperative management. The 12 players were allowed to return to play without the need for subsequent surgery within the same season. In the evaluation of return to play, based on the severity of the midfoot sprain, there was a statistically significant (P = .047) difference in mean (SD) time lost from participation between the grade 1 sprain group, 3.1 (1.9) days, and the grade 2 sprain group, 36 (26.1) days. Overall, nonoperative treatment of either grade 1 or grade 2 midfoot sprains resulted in a mean of 11.7 days of time lost from participation. In 1 patient with a grade 2 midfoot sprain, the injury occurred toward the end of the season, and the patient was not able to return to play during the remaining 42 days of the season. However, this patient returned to play the next season and had no residual problems.

Three grade 3 injuries (midfoot sprains with frank displacement) required surgical management with ORIF. One patient returned to play the same season, in 73 days; however, the other 2 patients had injuries toward the end of the season (29 and 77 days remaining) and were not able to return to play the same season. However, both these patients returned to play the next season and had no persistent problems. In terms of complications within the same season, there were no recurrent injuries reported after successful return to play.

When evaluating long-term postinjury playing status, we found that 11 (92%) of the 12 NFL players who had nonoperative treatment successfully returned to play. The only player who did not return to an NFL regular season or postseason game was an active-roster NFL player who never actually played in an NFL game before or after his midfoot sprain injury. Our series of NFL players played on average 1.9 years (range, 0-7 years) before the midfoot injury and 5.5 years (range, 0-14 years) after the midfoot injury. In terms of NFL regular-season and postseason games played, our cohort of NFL players played on average 24.0 games (range, 0-80 games) before the midfoot injury and 77.7 games (range, 0-226 games) after the midfoot injury. In fact, 10 of the 12 NFL players (83%) who had nonoperative treatment played more games and seasons after their midfoot injury.

The surveys from phase 2 were completed by all 32 NFL team physicians. When evaluating the severity of midfoot sprains, 63% of the NFL team physicians perform stress-view radiographs. To ascertain NFL team physicians’ management decisions, we evaluated midfoot sprain results according to injury severity, including amount of diastasis.

When managing midfoot sprains with no diastasis, 94% of the team physicians use immobilization, including 27 with a cam walker and 2 with a cast; however, 2 physicians (6%) use only ankle taping or an Ace bandage. Initial weight-bearing status varies among the NFL team physicians, but most (78%) choose to protect the player, including 17 non-weight-bearing, 8 partial weight-bearing, and 7 weight-bearing as tolerated. Most physicians ideally progress players to full weight-bearing by 3 weeks (12% immediately, 12% by week 1, 41% by week 2, 16% by week 3, and 19% from 4-6 weeks).

In the management of midfoot sprains with subtle diastasis, there is variation in treatment modes among the NFL team physicians, with 53% using nonoperative management (34% cam walker, 19% cast) and 47% suggesting operative management. Regardless of treatment, most physicians (97%) maintain initial non-weight-bearing restrictions. In fact, only 1 physician first recommended partial weight-bearing, which corresponded to initial treatment in a cam walker.

In terms of midfoot sprains with frank diastasis, 94% of the NFL team physicians indicated surgical management is warranted, with only 2 physicians (6%) recommending initial nonoperative management with a cam walker. Regardless of treatment, all the physicians (100%) implemented initial non-weight-bearing restrictions. Once surgical treatment was recommended, the preferred fixation method was ORIF using screws (94%) as opposed to closed reduction and internal fixation with percutaneous Kirschner wires (6%). Most of the physicians (59%) do not allow return to play until midfoot hardware is removed; however, 38% allow full participation with contact, and 3% allow partial participation with no contact. Removal of midfoot fixation is an important factor for most of the physicians before considering return to play, and 69% recommend hardware removal after 11 weeks. However, the specific timeline for hardware removal varied among these physicians, with 28% opting for removal at 11 to 12 weeks, 16% at 13 to 14 weeks, 12.5% at 7 to 8 weeks, 12.5% at 15 to 16 weeks, 12.5% at more than 16 weeks, 12.5% never, and 6% at 9 to 10 weeks.

The midfoot sprain treatment protocol (nonoperative vs operative management) based on injury severity was an important factor in considering return-to-play guidelines. When evaluating time lost from participation because of midfoot sprains, most of the NFL team physicians anticipated a period of 5 to 8 weeks when considering nonoperative management (56%) and more than 17 weeks after operative management (53%). In evaluating nonoperative management protocols, return-to-play guidelines were relatively expeditious, with 56% of the physicians estimating from 5 to 8 weeks, 22% from 1 to 4 weeks, 13% from 9 to 12 weeks, 6% from 13 to 16 weeks, and 3% longer than 20 weeks. In comparison to nonoperative management, return-to-play guidelines for operative management were prolonged, with 53% of the physicians estimating more than 20 weeks, 25% from 17 to 20 weeks, 13% from 13 to 16 weeks, and 9% from 9 to 12 weeks.

Discussion

Lisfranc and midfoot injuries remain a controversial topic in sports medicine. Several authors have argued that anatomical reduction of the tarsometatarsal joint in the setting of a Lisfranc injury yields optimal outcomes.^15,16 Some studies have also suggested that purely ligamentous Lisfranc injuries may be more of a problem than bony injuries, which may have the benefit of osseous healing.^15,17 Anatomical reduction can minimize the potential for arch collapse by maintaining the normal tarsometatarsal relationship. However, there are no long-term data to determine how midfoot arthrosis is affected by ORIF, which typically involves hardware traversing joints. Some have even argued that primary tarsometatarsal arthrodesis should be the treatment of choice, as the midfoot has limited native motion, and successful arthrodesis eliminates the potential for midfoot arthrosis.^17,18 However, we are unaware of any studies that have routinely performed arthrodesis in an athletic population.

The majority of studies on midfoot injuries have evaluated individuals involved in traumatic accidents, most commonly motor vehicle collisions. The present study suggests there may be a subset of injuries in athletes that have yet to be adequately studied. Anecdotally, the NFL team physicians surveyed in our study suggested that midfoot sprains with no or subtle displacement may be treated with nonoperative measures while yielding satisfactory clinical outcomes. These results have been quantified in return-to-play status. Our subset of athletes from an NFL team corroborates these findings, even though the series was small (15 patients). Our survey results also suggest there is considerable variation in the “optimal” management plan among the physicians treating these elite athletes. Most would agree that the nondisplaced injuries can be managed conservatively and that the severely displaced injuries should be managed operatively, but the natural history of those injuries with subtle diastasis remains unclear. When operative intervention is implemented, hardware removal versus retention must also be considered when allowing for return to play. Although one would assume that motion-related hardware failure would be possible at the tarsometatarsal joints, this concept has yet to be clearly defined in the literature.

The present study also demonstrates that most athletes with these midfoot injuries can return to play at the elite NFL level, as evidenced by their short- and long-term return to play. However, it was not possible to differentiate the specific return-to-play level related to preinjury performance level. Furthermore, this relatively short-term NFL career follow-up study was not able to elucidate the long-term consequences of these injuries. In fact, arch collapse and acquired flatfoot deformity could eventually result from this injury, and long-term outcomes would be of particular interest in patients who have subtle diastasis and who are treated nonoperatively.

Although previous studies have supported operative management for Lisfranc injuries involving subtle diastasis, more than half of the NFL team physicians surveyed in this study use nonoperative treatment for these injuries.¹⁹ Future studies should evaluate stress-imaging to define the effect of stability or latent diastasis on long-term outcomes. Nonetheless, the present study demonstrates that a large cohort of NFL team physicians supports nonoperative management for these Lisfranc injuries with subtle diastasis, even in elite athletes. Additional prospective studies are needed to provide a more rigorous injury evaluation and closer follow-up, including subjective and objective outcomes, to further define the indications for management options for midfoot sprains in this population of contact athletes.