SAN FRANCISCO – At 5 years, the rates of disabling stroke or death were similar among patients with severe aortic stenosis and intermediate surgical risk who underwent transcatheter aortic valve replacement or surgical aortic valve replacement.

Doug Brunk/MDedge News

At the same time, patients who underwent TAVR using a transthoracic approach had poorer outcomes, compared with their counterparts who underwent SAVR, Vinod H. Thourani, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting. The findings come from an analysis of the PARTNER 2A trial, the largest randomized study ever conducted in the field of TAVR and SAVR.

In an effort to compare the key clinical outcomes, bioprosthetic valve function, and quality-of-life measures at 5 years for TAVR versus surgery, Dr. Thourani and his colleagues used data from 2,032 intermediate-risk patients with severe AS assigned to either TAVR or SAVR at 57 centers in the PARTNER 2A trial. Their mean age was 82 years, and their average Society of Thoracic Surgery risk score was 5.8%. The 2-year primary endpoint was all-cause death or disabling stroke in the intention-to-treat (ITT) population. At 5 years, the researchers analyzed all primary and secondary clinical and echo endpoints in both ITT and prespecified as-treated populations.

At 5 years, the primary endpoint of death and disabling stroke at 5 years was 47.9% in the TAVR group and 43.4% in the surgery group, a difference that did not reach statistical significance (hazard ratio, 1.09; P = .21). In the transfemoral cohort, rates of the primary endpoint were also similar between TAVR and SAVR (44.5% vs. 42%, respectively; HR, 1.02; P = .80). In the transthoracic cohort, however, the researchers observed a divergence in the primary outcome starting at year 1, such that it was higher with TAVR at 5 years, compared with SAVR (59.3% vs. 48.3%; P = .03), reported Dr. Thourani, chair of cardiac surgery at Medstar Heart and Vascular Institute, Washington.

When he and his colleagues examined freedom from aortic valve reintervention at 5 years, the hazard ratios showed some difference between TAVR and SAVR (HR, 3.93; P = .003), yet clinically the freedom from reintervention rate was very high (96.8% vs. 99.4%, respectively). “The other issue we’ve been interested in is the difference between mean aortic valve gradients between the groups,” Dr. Thourani said at the meeting. “There was no difference in mean aortic valve gradients between TAVR and SAVR at 5 years (a mean of 11.4 mm Hg vs. 10.8 mm Hg, respectively; P = .23).”

Paravalvular regurgitation (PVR) was more common in the TAVR vs. SAVR group at all follow-up times (P less than .001 in all categories). By year 5, the proportion of patients with moderate to severe PVR was 6.5% in the TAVR group vs. 0.4% in the SAVR group, respectively, while the proportion of those with mild PVR was 26.8%, compared with 5.9%.

In other findings, no difference in mortality was seen in the TAVR cohort between those with mild PVR and no or trace PVR (48.7% vs. 41.1%; P = .07). However, those with moderate to severe PVR at the end of the procedure had an increased mortality at the end of 5 years (64.8%; P = .007). “If you had none or trace PVR at baseline, there was no major difference in mortality between the two groups at 2 years,” Dr. Thourani said. “That difference was maintained at 5 years.”

The overall findings, he continued, support the notion that TAVR should be considered as an alternative to surgery in intermediate-risk patients with severe aortic stenosis. “However, in patients without acceptable transfemoral access, surgery may be the preferred alternative,” he said.

Roxana Mehran, MD,, director of interventional cardiovascular research and clinical trials at Mount Sinai School of Medicine, New York, commented that the reassurance of the same outcomes at 5 years between the two approaches “makes TAVR superior. It’s a less invasive and durable result. One of the things we have yet to figure out is the need for anticoagulation to prevent stroke in these patients. We have very little data and understanding about that.”

The PARTNER 2A study was funded by Edwards Lifesciences. Dr. Thourani has received grant or research support from and participation in steering committees for Edwards Lifesciences, Abbott Vascular, Boston Scientific, Gore Vascular, JenaValve, and Cryolife.

[email protected]

SAN FRANCISCO – At 5 years, the rates of disabling stroke or death were similar among patients with severe aortic stenosis and intermediate surgical risk who underwent transcatheter aortic valve replacement or surgical aortic valve replacement.

Doug Brunk/MDedge News

At the same time, patients who underwent TAVR using a transthoracic approach had poorer outcomes, compared with their counterparts who underwent SAVR, Vinod H. Thourani, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting. The findings come from an analysis of the PARTNER 2A trial, the largest randomized study ever conducted in the field of TAVR and SAVR.

In an effort to compare the key clinical outcomes, bioprosthetic valve function, and quality-of-life measures at 5 years for TAVR versus surgery, Dr. Thourani and his colleagues used data from 2,032 intermediate-risk patients with severe AS assigned to either TAVR or SAVR at 57 centers in the PARTNER 2A trial. Their mean age was 82 years, and their average Society of Thoracic Surgery risk score was 5.8%. The 2-year primary endpoint was all-cause death or disabling stroke in the intention-to-treat (ITT) population. At 5 years, the researchers analyzed all primary and secondary clinical and echo endpoints in both ITT and prespecified as-treated populations.

At 5 years, the primary endpoint of death and disabling stroke at 5 years was 47.9% in the TAVR group and 43.4% in the surgery group, a difference that did not reach statistical significance (hazard ratio, 1.09; P = .21). In the transfemoral cohort, rates of the primary endpoint were also similar between TAVR and SAVR (44.5% vs. 42%, respectively; HR, 1.02; P = .80). In the transthoracic cohort, however, the researchers observed a divergence in the primary outcome starting at year 1, such that it was higher with TAVR at 5 years, compared with SAVR (59.3% vs. 48.3%; P = .03), reported Dr. Thourani, chair of cardiac surgery at Medstar Heart and Vascular Institute, Washington.

When he and his colleagues examined freedom from aortic valve reintervention at 5 years, the hazard ratios showed some difference between TAVR and SAVR (HR, 3.93; P = .003), yet clinically the freedom from reintervention rate was very high (96.8% vs. 99.4%, respectively). “The other issue we’ve been interested in is the difference between mean aortic valve gradients between the groups,” Dr. Thourani said at the meeting. “There was no difference in mean aortic valve gradients between TAVR and SAVR at 5 years (a mean of 11.4 mm Hg vs. 10.8 mm Hg, respectively; P = .23).”

Paravalvular regurgitation (PVR) was more common in the TAVR vs. SAVR group at all follow-up times (P less than .001 in all categories). By year 5, the proportion of patients with moderate to severe PVR was 6.5% in the TAVR group vs. 0.4% in the SAVR group, respectively, while the proportion of those with mild PVR was 26.8%, compared with 5.9%.

In other findings, no difference in mortality was seen in the TAVR cohort between those with mild PVR and no or trace PVR (48.7% vs. 41.1%; P = .07). However, those with moderate to severe PVR at the end of the procedure had an increased mortality at the end of 5 years (64.8%; P = .007). “If you had none or trace PVR at baseline, there was no major difference in mortality between the two groups at 2 years,” Dr. Thourani said. “That difference was maintained at 5 years.”

The overall findings, he continued, support the notion that TAVR should be considered as an alternative to surgery in intermediate-risk patients with severe aortic stenosis. “However, in patients without acceptable transfemoral access, surgery may be the preferred alternative,” he said.

Roxana Mehran, MD,, director of interventional cardiovascular research and clinical trials at Mount Sinai School of Medicine, New York, commented that the reassurance of the same outcomes at 5 years between the two approaches “makes TAVR superior. It’s a less invasive and durable result. One of the things we have yet to figure out is the need for anticoagulation to prevent stroke in these patients. We have very little data and understanding about that.”

The PARTNER 2A study was funded by Edwards Lifesciences. Dr. Thourani has received grant or research support from and participation in steering committees for Edwards Lifesciences, Abbott Vascular, Boston Scientific, Gore Vascular, JenaValve, and Cryolife.

[email protected]

SAN FRANCISCO – At 5 years, the rates of disabling stroke or death were similar among patients with severe aortic stenosis and intermediate surgical risk who underwent transcatheter aortic valve replacement or surgical aortic valve replacement.

Doug Brunk/MDedge News

At the same time, patients who underwent TAVR using a transthoracic approach had poorer outcomes, compared with their counterparts who underwent SAVR, Vinod H. Thourani, MD, reported at the Transcatheter Cardiovascular Therapeutics annual meeting. The findings come from an analysis of the PARTNER 2A trial, the largest randomized study ever conducted in the field of TAVR and SAVR.

In an effort to compare the key clinical outcomes, bioprosthetic valve function, and quality-of-life measures at 5 years for TAVR versus surgery, Dr. Thourani and his colleagues used data from 2,032 intermediate-risk patients with severe AS assigned to either TAVR or SAVR at 57 centers in the PARTNER 2A trial. Their mean age was 82 years, and their average Society of Thoracic Surgery risk score was 5.8%. The 2-year primary endpoint was all-cause death or disabling stroke in the intention-to-treat (ITT) population. At 5 years, the researchers analyzed all primary and secondary clinical and echo endpoints in both ITT and prespecified as-treated populations.

At 5 years, the primary endpoint of death and disabling stroke at 5 years was 47.9% in the TAVR group and 43.4% in the surgery group, a difference that did not reach statistical significance (hazard ratio, 1.09; P = .21). In the transfemoral cohort, rates of the primary endpoint were also similar between TAVR and SAVR (44.5% vs. 42%, respectively; HR, 1.02; P = .80). In the transthoracic cohort, however, the researchers observed a divergence in the primary outcome starting at year 1, such that it was higher with TAVR at 5 years, compared with SAVR (59.3% vs. 48.3%; P = .03), reported Dr. Thourani, chair of cardiac surgery at Medstar Heart and Vascular Institute, Washington.

When he and his colleagues examined freedom from aortic valve reintervention at 5 years, the hazard ratios showed some difference between TAVR and SAVR (HR, 3.93; P = .003), yet clinically the freedom from reintervention rate was very high (96.8% vs. 99.4%, respectively). “The other issue we’ve been interested in is the difference between mean aortic valve gradients between the groups,” Dr. Thourani said at the meeting. “There was no difference in mean aortic valve gradients between TAVR and SAVR at 5 years (a mean of 11.4 mm Hg vs. 10.8 mm Hg, respectively; P = .23).”

Paravalvular regurgitation (PVR) was more common in the TAVR vs. SAVR group at all follow-up times (P less than .001 in all categories). By year 5, the proportion of patients with moderate to severe PVR was 6.5% in the TAVR group vs. 0.4% in the SAVR group, respectively, while the proportion of those with mild PVR was 26.8%, compared with 5.9%.

In other findings, no difference in mortality was seen in the TAVR cohort between those with mild PVR and no or trace PVR (48.7% vs. 41.1%; P = .07). However, those with moderate to severe PVR at the end of the procedure had an increased mortality at the end of 5 years (64.8%; P = .007). “If you had none or trace PVR at baseline, there was no major difference in mortality between the two groups at 2 years,” Dr. Thourani said. “That difference was maintained at 5 years.”

The overall findings, he continued, support the notion that TAVR should be considered as an alternative to surgery in intermediate-risk patients with severe aortic stenosis. “However, in patients without acceptable transfemoral access, surgery may be the preferred alternative,” he said.

Roxana Mehran, MD,, director of interventional cardiovascular research and clinical trials at Mount Sinai School of Medicine, New York, commented that the reassurance of the same outcomes at 5 years between the two approaches “makes TAVR superior. It’s a less invasive and durable result. One of the things we have yet to figure out is the need for anticoagulation to prevent stroke in these patients. We have very little data and understanding about that.”

The PARTNER 2A study was funded by Edwards Lifesciences. Dr. Thourani has received grant or research support from and participation in steering committees for Edwards Lifesciences, Abbott Vascular, Boston Scientific, Gore Vascular, JenaValve, and Cryolife.

[email protected]

The FP suspected that the child had morphea because the skin was somewhat firm and thickened, and there was hypo- and hyperpigmentation.

Morphea is a localized type of scleroderma and may be seen in children. Fortunately, it does not involve the internal organs. There are no blood tests needed for the diagnosis and antinuclear antibodies should be normal. While a punch biopsy could be considered in less obvious cases in older children, it is probably unnecessary to put a 5-year-old child through the trauma of a biopsy.

The FP referred the child to a dermatologist to confirm the diagnosis and initiate treatment. Typical treatments include topical mid- to high-potency steroids and/or topical calcineurin inhibitors.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux EJ, Usatine R. Scleroderma and morphea. In: Usatine R, Smith M, Mayeaux EJ, Chumley H. eds. Color Atlas and Synopsis of Family Medicine, 3rd Edition. New York, NY: McGraw-Hill; 2019:1204-1212.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the 3rd edition of the Color Atlas and Synopsis of Family Medicine as an app by clicking on this link: https://usatinemedia.com/app/color-atlas-of-family-medicine/

The FP suspected that the child had morphea because the skin was somewhat firm and thickened, and there was hypo- and hyperpigmentation.

Morphea is a localized type of scleroderma and may be seen in children. Fortunately, it does not involve the internal organs. There are no blood tests needed for the diagnosis and antinuclear antibodies should be normal. While a punch biopsy could be considered in less obvious cases in older children, it is probably unnecessary to put a 5-year-old child through the trauma of a biopsy.

The FP referred the child to a dermatologist to confirm the diagnosis and initiate treatment. Typical treatments include topical mid- to high-potency steroids and/or topical calcineurin inhibitors.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux EJ, Usatine R. Scleroderma and morphea. In: Usatine R, Smith M, Mayeaux EJ, Chumley H. eds. Color Atlas and Synopsis of Family Medicine, 3rd Edition. New York, NY: McGraw-Hill; 2019:1204-1212.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the 3rd edition of the Color Atlas and Synopsis of Family Medicine as an app by clicking on this link: https://usatinemedia.com/app/color-atlas-of-family-medicine/

The FP suspected that the child had morphea because the skin was somewhat firm and thickened, and there was hypo- and hyperpigmentation.

Morphea is a localized type of scleroderma and may be seen in children. Fortunately, it does not involve the internal organs. There are no blood tests needed for the diagnosis and antinuclear antibodies should be normal. While a punch biopsy could be considered in less obvious cases in older children, it is probably unnecessary to put a 5-year-old child through the trauma of a biopsy.

The FP referred the child to a dermatologist to confirm the diagnosis and initiate treatment. Typical treatments include topical mid- to high-potency steroids and/or topical calcineurin inhibitors.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Mayeaux EJ, Usatine R. Scleroderma and morphea. In: Usatine R, Smith M, Mayeaux EJ, Chumley H. eds. Color Atlas and Synopsis of Family Medicine, 3rd Edition. New York, NY: McGraw-Hill; 2019:1204-1212.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the 3rd edition of the Color Atlas and Synopsis of Family Medicine as an app by clicking on this link: https://usatinemedia.com/app/color-atlas-of-family-medicine/

Trial success with a stereotactic body radiation therapy (SBRT) regimen for centrally located non–small cell lung cancer (NSCLC) can be largely replicated in real-world practice, suggests a prospective cohort study published in Clinical Oncology.

The Radiation Therapy Oncology Group (RTOG) 0813 trial established the safety and efficacy of 50 Gy or 60 Gy given in five fractions to patients with early-stage central NSCLC (J Clin Oncol. 2019;37:1316-25). But whether similar outcomes can be achieved in routine care and how the degree of tumor centrality affects outcomes remain unclear.

Investigators led by Robert Rulach, MBChB, from the Beatson West of Scotland Cancer Centre, Glasgow, analyzed outcomes for 50 patients treated with the regimen of 50-Gy in five fractions at their institution for T1-2N0M0 stage NSCLC. All had tumors that were moderately central (within 2 cm of the trachea, bronchi, or proximal bronchial tree or having a planning target volume that abutted mediastinal pleura or pericardium); one had an additional tumor that was ultracentral (having a planning target volume that abutted the trachea).

The patients had a median age of 75.1 years. Notably, the majority were medically unfit for surgery (84%) and had an Eastern Cooperative Oncology Group performance status score of 2 or worse (56%). In 60% of patients, the diagnosis was made radiographically using PET/CT imaging; in the rest, the diagnosis was biopsy proven.

Study results showed that all patients completed the radiotherapy regimen of 50 Gy in 5 fractions on alternate days as planned, without treatment delays.

Two patients (4%) died within 90 days of treatment (1 from a chest infection, 1 from an unknown cause). A single patient each experienced early grade 3 esophagitis and grade 3 late dyspnea, for an overall rate of grade 3 toxicity of 4%. None of the patients experienced grade 4 toxicity. The 90-day rate of hospital admission was 20%.

With a median follow-up of 25.2 months, 34 patients died: 18 from causes unrelated to cancer and 16 from cancer recurrence. The cohort had a median overall survival of 27.0 months and a median cancer-specific survival of 39.8 months. The 2-year overall survival rate was 67.6%.

“For patients with early stage moderately central NSCLC, SABR [stereotactic ablative body radiotherapy] using a schedule of 50 Gy/five fractions has acceptable toxicity and overall survival comparable with the published literature, despite treating a majority of patients with a performance status of 2 or worse,” the investigators concluded.

Dr. Rulach disclosed no conflicts of interest. The study did not receive any specific funding.

SOURCE: Rulach R et al. Clin Oncol. 2019 Oct 10. doi: 10.1016/j.clon.2019.09.055.

Trial success with a stereotactic body radiation therapy (SBRT) regimen for centrally located non–small cell lung cancer (NSCLC) can be largely replicated in real-world practice, suggests a prospective cohort study published in Clinical Oncology.

The Radiation Therapy Oncology Group (RTOG) 0813 trial established the safety and efficacy of 50 Gy or 60 Gy given in five fractions to patients with early-stage central NSCLC (J Clin Oncol. 2019;37:1316-25). But whether similar outcomes can be achieved in routine care and how the degree of tumor centrality affects outcomes remain unclear.

Investigators led by Robert Rulach, MBChB, from the Beatson West of Scotland Cancer Centre, Glasgow, analyzed outcomes for 50 patients treated with the regimen of 50-Gy in five fractions at their institution for T1-2N0M0 stage NSCLC. All had tumors that were moderately central (within 2 cm of the trachea, bronchi, or proximal bronchial tree or having a planning target volume that abutted mediastinal pleura or pericardium); one had an additional tumor that was ultracentral (having a planning target volume that abutted the trachea).

The patients had a median age of 75.1 years. Notably, the majority were medically unfit for surgery (84%) and had an Eastern Cooperative Oncology Group performance status score of 2 or worse (56%). In 60% of patients, the diagnosis was made radiographically using PET/CT imaging; in the rest, the diagnosis was biopsy proven.

Study results showed that all patients completed the radiotherapy regimen of 50 Gy in 5 fractions on alternate days as planned, without treatment delays.

Two patients (4%) died within 90 days of treatment (1 from a chest infection, 1 from an unknown cause). A single patient each experienced early grade 3 esophagitis and grade 3 late dyspnea, for an overall rate of grade 3 toxicity of 4%. None of the patients experienced grade 4 toxicity. The 90-day rate of hospital admission was 20%.

With a median follow-up of 25.2 months, 34 patients died: 18 from causes unrelated to cancer and 16 from cancer recurrence. The cohort had a median overall survival of 27.0 months and a median cancer-specific survival of 39.8 months. The 2-year overall survival rate was 67.6%.

“For patients with early stage moderately central NSCLC, SABR [stereotactic ablative body radiotherapy] using a schedule of 50 Gy/five fractions has acceptable toxicity and overall survival comparable with the published literature, despite treating a majority of patients with a performance status of 2 or worse,” the investigators concluded.

Dr. Rulach disclosed no conflicts of interest. The study did not receive any specific funding.

SOURCE: Rulach R et al. Clin Oncol. 2019 Oct 10. doi: 10.1016/j.clon.2019.09.055.

Trial success with a stereotactic body radiation therapy (SBRT) regimen for centrally located non–small cell lung cancer (NSCLC) can be largely replicated in real-world practice, suggests a prospective cohort study published in Clinical Oncology.

The Radiation Therapy Oncology Group (RTOG) 0813 trial established the safety and efficacy of 50 Gy or 60 Gy given in five fractions to patients with early-stage central NSCLC (J Clin Oncol. 2019;37:1316-25). But whether similar outcomes can be achieved in routine care and how the degree of tumor centrality affects outcomes remain unclear.

Investigators led by Robert Rulach, MBChB, from the Beatson West of Scotland Cancer Centre, Glasgow, analyzed outcomes for 50 patients treated with the regimen of 50-Gy in five fractions at their institution for T1-2N0M0 stage NSCLC. All had tumors that were moderately central (within 2 cm of the trachea, bronchi, or proximal bronchial tree or having a planning target volume that abutted mediastinal pleura or pericardium); one had an additional tumor that was ultracentral (having a planning target volume that abutted the trachea).

The patients had a median age of 75.1 years. Notably, the majority were medically unfit for surgery (84%) and had an Eastern Cooperative Oncology Group performance status score of 2 or worse (56%). In 60% of patients, the diagnosis was made radiographically using PET/CT imaging; in the rest, the diagnosis was biopsy proven.

Study results showed that all patients completed the radiotherapy regimen of 50 Gy in 5 fractions on alternate days as planned, without treatment delays.

Two patients (4%) died within 90 days of treatment (1 from a chest infection, 1 from an unknown cause). A single patient each experienced early grade 3 esophagitis and grade 3 late dyspnea, for an overall rate of grade 3 toxicity of 4%. None of the patients experienced grade 4 toxicity. The 90-day rate of hospital admission was 20%.

With a median follow-up of 25.2 months, 34 patients died: 18 from causes unrelated to cancer and 16 from cancer recurrence. The cohort had a median overall survival of 27.0 months and a median cancer-specific survival of 39.8 months. The 2-year overall survival rate was 67.6%.

“For patients with early stage moderately central NSCLC, SABR [stereotactic ablative body radiotherapy] using a schedule of 50 Gy/five fractions has acceptable toxicity and overall survival comparable with the published literature, despite treating a majority of patients with a performance status of 2 or worse,” the investigators concluded.

Dr. Rulach disclosed no conflicts of interest. The study did not receive any specific funding.

SOURCE: Rulach R et al. Clin Oncol. 2019 Oct 10. doi: 10.1016/j.clon.2019.09.055.

WASHINGTON – The practice of medicine needs a major reset to address the stresses that lead to clinician burnout, a condition now estimated to affect a third to a half of clinicians in the United States, according to a report from an influential federal panel.

The National Academy of Medicine (NAM) on Oct. 23 released a report, “Taking Action Against Clinician Burnout: A Systems Approach to Professional Well-Being.” The report calls for a broad and unified approach to tackling the root causes of burnout.

There must be a concerted effort by leaders of many fields of health care to create less stressful workplaces for clinicians, Pascale Carayon, PhD, cochair of the NAM committee that produced the report, said during the NAM press event.

“This is not an easy process,” said Dr. Carayon, a researcher into patient safety issues at the University of Wisconsin–Madison. “There is no single solution.”

The NAM report assigns specific tasks to many different participants in health care through a six-goal approach, as described below.

–Create positive workplaces. Leaders of health care systems should consider how their business and management decisions will affect clinicians’ jobs, taking into account the potential to add to their levels of burnout. Executives need to continuously monitor and evaluate the extent of burnout in their organizations, and report on this at least annually.

–Address burnout in training and in clinicians’ early years. Medical, nursing, and pharmacy schools should consider steps such as monitoring workload, implementing pass-fail grading, improving access to scholarships and affordable loans, and creating new loan repayment systems.

–Reduce administrative burden. Federal and state bodies and organizations such as the National Quality Forum should reconsider how their regulations and recommendations contribute to burnout. Organizations should seek to eliminate tasks that do not improve the care of patients.

–Improve usability and relevance of health information technology (IT). Medical organizations should develop and buy systems that are as user-friendly and easy to operate as possible. They also should look to use IT to reduce documentation demands and automate nonessential tasks.

–Reduce stigma and improve burnout recovery services. State officials and legislative bodies should make it easier for clinicians to use employee assistance programs, peer support programs, and mental health providers without the information being admissible in malpractice litigation. The report notes the recommendations from the Federation of State Medical Boards, American Medical Association, and the American Psychiatric Association on limiting inquiries in licensing applications about a clinician’s mental health. Questions should focus on current impairment rather than reach well into a clinician’s past.

–Create a national research agenda on clinician well-being. By the end of 2020, federal agencies – including the Agency for Healthcare Research and Quality, the National Institute for Occupational Safety and Health, the Health Resources and Services Administration, and the U.S. Department of Veterans Affairs – should develop a coordinated research agenda on clinician burnout, the report said.

In casting a wide net and assigning specific tasks, the NAM report seeks to establish efforts to address clinician burnout as a broad and shared responsibility. It would be too easy for different medical organizations to depict addressing burnout as being outside of their responsibilities, Christine K. Cassel, MD, the cochair of the NAM committee that produced the report, said during the press event.

WASHINGTON – The practice of medicine needs a major reset to address the stresses that lead to clinician burnout, a condition now estimated to affect a third to a half of clinicians in the United States, according to a report from an influential federal panel.

The National Academy of Medicine (NAM) on Oct. 23 released a report, “Taking Action Against Clinician Burnout: A Systems Approach to Professional Well-Being.” The report calls for a broad and unified approach to tackling the root causes of burnout.

There must be a concerted effort by leaders of many fields of health care to create less stressful workplaces for clinicians, Pascale Carayon, PhD, cochair of the NAM committee that produced the report, said during the NAM press event.

“This is not an easy process,” said Dr. Carayon, a researcher into patient safety issues at the University of Wisconsin–Madison. “There is no single solution.”

The NAM report assigns specific tasks to many different participants in health care through a six-goal approach, as described below.

–Create positive workplaces. Leaders of health care systems should consider how their business and management decisions will affect clinicians’ jobs, taking into account the potential to add to their levels of burnout. Executives need to continuously monitor and evaluate the extent of burnout in their organizations, and report on this at least annually.

–Address burnout in training and in clinicians’ early years. Medical, nursing, and pharmacy schools should consider steps such as monitoring workload, implementing pass-fail grading, improving access to scholarships and affordable loans, and creating new loan repayment systems.

–Reduce administrative burden. Federal and state bodies and organizations such as the National Quality Forum should reconsider how their regulations and recommendations contribute to burnout. Organizations should seek to eliminate tasks that do not improve the care of patients.

–Improve usability and relevance of health information technology (IT). Medical organizations should develop and buy systems that are as user-friendly and easy to operate as possible. They also should look to use IT to reduce documentation demands and automate nonessential tasks.

–Reduce stigma and improve burnout recovery services. State officials and legislative bodies should make it easier for clinicians to use employee assistance programs, peer support programs, and mental health providers without the information being admissible in malpractice litigation. The report notes the recommendations from the Federation of State Medical Boards, American Medical Association, and the American Psychiatric Association on limiting inquiries in licensing applications about a clinician’s mental health. Questions should focus on current impairment rather than reach well into a clinician’s past.

–Create a national research agenda on clinician well-being. By the end of 2020, federal agencies – including the Agency for Healthcare Research and Quality, the National Institute for Occupational Safety and Health, the Health Resources and Services Administration, and the U.S. Department of Veterans Affairs – should develop a coordinated research agenda on clinician burnout, the report said.

In casting a wide net and assigning specific tasks, the NAM report seeks to establish efforts to address clinician burnout as a broad and shared responsibility. It would be too easy for different medical organizations to depict addressing burnout as being outside of their responsibilities, Christine K. Cassel, MD, the cochair of the NAM committee that produced the report, said during the press event.

WASHINGTON – The practice of medicine needs a major reset to address the stresses that lead to clinician burnout, a condition now estimated to affect a third to a half of clinicians in the United States, according to a report from an influential federal panel.

The National Academy of Medicine (NAM) on Oct. 23 released a report, “Taking Action Against Clinician Burnout: A Systems Approach to Professional Well-Being.” The report calls for a broad and unified approach to tackling the root causes of burnout.

There must be a concerted effort by leaders of many fields of health care to create less stressful workplaces for clinicians, Pascale Carayon, PhD, cochair of the NAM committee that produced the report, said during the NAM press event.

“This is not an easy process,” said Dr. Carayon, a researcher into patient safety issues at the University of Wisconsin–Madison. “There is no single solution.”

The NAM report assigns specific tasks to many different participants in health care through a six-goal approach, as described below.

–Create positive workplaces. Leaders of health care systems should consider how their business and management decisions will affect clinicians’ jobs, taking into account the potential to add to their levels of burnout. Executives need to continuously monitor and evaluate the extent of burnout in their organizations, and report on this at least annually.

–Address burnout in training and in clinicians’ early years. Medical, nursing, and pharmacy schools should consider steps such as monitoring workload, implementing pass-fail grading, improving access to scholarships and affordable loans, and creating new loan repayment systems.

–Reduce administrative burden. Federal and state bodies and organizations such as the National Quality Forum should reconsider how their regulations and recommendations contribute to burnout. Organizations should seek to eliminate tasks that do not improve the care of patients.

–Improve usability and relevance of health information technology (IT). Medical organizations should develop and buy systems that are as user-friendly and easy to operate as possible. They also should look to use IT to reduce documentation demands and automate nonessential tasks.

–Reduce stigma and improve burnout recovery services. State officials and legislative bodies should make it easier for clinicians to use employee assistance programs, peer support programs, and mental health providers without the information being admissible in malpractice litigation. The report notes the recommendations from the Federation of State Medical Boards, American Medical Association, and the American Psychiatric Association on limiting inquiries in licensing applications about a clinician’s mental health. Questions should focus on current impairment rather than reach well into a clinician’s past.

–Create a national research agenda on clinician well-being. By the end of 2020, federal agencies – including the Agency for Healthcare Research and Quality, the National Institute for Occupational Safety and Health, the Health Resources and Services Administration, and the U.S. Department of Veterans Affairs – should develop a coordinated research agenda on clinician burnout, the report said.

In casting a wide net and assigning specific tasks, the NAM report seeks to establish efforts to address clinician burnout as a broad and shared responsibility. It would be too easy for different medical organizations to depict addressing burnout as being outside of their responsibilities, Christine K. Cassel, MD, the cochair of the NAM committee that produced the report, said during the press event.

I have always enjoyed talking with my patients from coastal Louisiana. They enjoy life, embrace their environment, and give me a perspective which is both similar and different than that of residents of New Orleans where I practice hospital medicine.

Bernhard_Staehli/Thinkstock

Their hospitalization is often a reflective moment in their lives. Lately I have been asking them about their advice to their children concerning the future of southern Louisiana in reference to sea rise, global warming, and increasing climatic events. More often than not, they have been telling their children it is time to move away.

These are a people who have strong devotion to family, but they are also practical. More than anything they would like their children to stay and preserve their heritage, but concern for their children’s future outweighs that. They have not come to this conclusion by scientific reports, but rather by what is happening before them. This group of people doesn’t alarm easily, but they see the unrelenting evidence of land loss and sea rise before them with little reason to believe it will change.

I am normally not one to speak out about climate change. Like most I have listened to the continuous alarms sounded by experts but have always assumed someone more qualified than myself should lead the efforts. But when I see the tangible effects of climate change both in my own life and the lives of my patients, I feel a sense of urgency.

12 years

Twelve years. That is the time we have to significantly reduce carbon emissions before catastrophic and potentially irreversible events will occur. This evidence is according to the authors of the landmark report by the UN Intergovernmental Panel on Climate Change released in October 2018. The report states urgent and unprecedented changes are needed to limit temperature elevations of 1.5°C and 2°C, as compared with the preindustrial era. Exceeding a 2°C elevation will likely lead to global adverse events at an unprecedented level.¹

The events forecast by the U.N. report are not abstract, particularly as they relate to public health. With high confidence, the report outlines with high specificity: increases in extreme heat, floods, crop failures, and a multitude of economic and social stressors which will affect the care of our most vulnerable patients.¹

This statement by Dr. Dana Hanson, president of the World Medical Association, summarizes the effects of climate change on the delivery of health care: “Climate change represents an inevitable massive threat to global health that will likely eclipse the major pandemics as a leading cause of death in the 21st century.”

So, what does the health care system have to do with climate change and its primary driver, carbon emissions? More than I realized, as the U.S. health care industry produces 10% of the nation’s carbon emissions.² If the U.S. health care system was a country it would be ranked seventh, ahead of the United Kingdom; 10% of all smog and 9% of all particulate-related respiratory disease can be attributed to the carbon emissions of the health care industry. This breaks down to possibly 20,000 premature deaths per year.² Our current health care industry is a significant driver of environmentally related disease and will continue to be so, unless major change occurs.

Although much of it is behind the scenes, providing health care 24/7 is a highly energy-intensive and waste-producing endeavor. Many of the innovations to reduce carbon emissions that have been seen in other industries have lagged behind in health care, as we have focused on other issues.

But the health care system is transitioning. It strives to address the whole person, including where they live, work, and play. A key component of this will be addressing our impact on the environments we serve. How can we make that argument if we don’t first address our own impact on the climate?

Carbon-neutral health care

Health care is one of the few industries that has the economic clout, the scientific basis, the community engagement, and perhaps most importantly the motivations to “first, do no harm” that could lead a national (if not a global) transformation in environmental stewardship among all industries.

Many agree that action is needed, but is essential that we set specific meaningful goals that take into account the urgency of the situation. One possible solution is to encourage every health care system to begin the process of becoming carbon neutral. Simply defined, carbon neutrality is balancing the activities that result in carbon emissions with activities that reduce carbon emissions. Carbon neutrality has become the standard by which an industry’s commitment to reducing carbon emissions is measured. The measurement is standardized and achievable, and the basic concept is understood by most. It results not only in long-term benefits to climate change, but immediate improvement of air quality in the local community. In addition, achieving carbon neutrality serves as a catalyst of new desired industries, improves employee morale, and aids in recruitment.³

So, what would a carbon-neutral health care system look like? In short, sustainability should be considered in all of its actions. Risks and benefits would be contemplated, as we do with all treatments, except now environmental risks would be brought into the equation. This includes the obvious, such as purchasing and supporting the development of renewable energy, but also transportation of patients and employees, food supply chains, and even the use of virtual visits to reduce the environmental impact of patient transportation.

I am optimistic that carbon neutrality is achievable in the health care sector. It can drive economic development and engage the community in environmental stewardship efforts. But time is of the essence and leaders for these efforts are needed now. As hospitalists, we are on the front lines of the health care system. We see the direct impact of social, economic, and environmental issues on our patients. We have credibility with both our patients and hospital administration. Among all industries, there need to be champions of environmental sustainability efforts. Hospitalists are uniquely positioned to fill that role.

My concern is that 12 years is right around the corner. We are at an inflection point on our efforts to reduce carbon emissions and that is good, but time has become our enemy. The difference between terrible and unlivable will be our, and the world’s, response to reducing carbon emissions.

It is time for bold action from us, the health care community. It is our moment and our place to lead those efforts, so let’s take advantage of both this challenge and this opportunity. Consider leading those efforts in your health care system.

Dr. Conrad is medical director of community affairs and health policy at Ochsner Health Systems in New Orleans.

References

1. Special Report on Global Warming of 1.5°C. Incheon [Republic of Korea]: Intergovernmental Panel on Climate Change. 7 Oct 2018.

2. Eckelman MJ, Sherman J. Environmental Impacts of the U.S. Health Care System and Effects on Public Health. PLoS ONE. 11(6):e0157014.

3. McCunn LJ, Gifford R. Do green offices affect employee engagement and environmental attitudes? Archit Sci Rev. 55:2;128-34. doi: 10.1080/00038628.2012.667939.
 

I have always enjoyed talking with my patients from coastal Louisiana. They enjoy life, embrace their environment, and give me a perspective which is both similar and different than that of residents of New Orleans where I practice hospital medicine.

Bernhard_Staehli/Thinkstock

Their hospitalization is often a reflective moment in their lives. Lately I have been asking them about their advice to their children concerning the future of southern Louisiana in reference to sea rise, global warming, and increasing climatic events. More often than not, they have been telling their children it is time to move away.

These are a people who have strong devotion to family, but they are also practical. More than anything they would like their children to stay and preserve their heritage, but concern for their children’s future outweighs that. They have not come to this conclusion by scientific reports, but rather by what is happening before them. This group of people doesn’t alarm easily, but they see the unrelenting evidence of land loss and sea rise before them with little reason to believe it will change.

I am normally not one to speak out about climate change. Like most I have listened to the continuous alarms sounded by experts but have always assumed someone more qualified than myself should lead the efforts. But when I see the tangible effects of climate change both in my own life and the lives of my patients, I feel a sense of urgency.

12 years

Twelve years. That is the time we have to significantly reduce carbon emissions before catastrophic and potentially irreversible events will occur. This evidence is according to the authors of the landmark report by the UN Intergovernmental Panel on Climate Change released in October 2018. The report states urgent and unprecedented changes are needed to limit temperature elevations of 1.5°C and 2°C, as compared with the preindustrial era. Exceeding a 2°C elevation will likely lead to global adverse events at an unprecedented level.¹

The events forecast by the U.N. report are not abstract, particularly as they relate to public health. With high confidence, the report outlines with high specificity: increases in extreme heat, floods, crop failures, and a multitude of economic and social stressors which will affect the care of our most vulnerable patients.¹

This statement by Dr. Dana Hanson, president of the World Medical Association, summarizes the effects of climate change on the delivery of health care: “Climate change represents an inevitable massive threat to global health that will likely eclipse the major pandemics as a leading cause of death in the 21st century.”

So, what does the health care system have to do with climate change and its primary driver, carbon emissions? More than I realized, as the U.S. health care industry produces 10% of the nation’s carbon emissions.² If the U.S. health care system was a country it would be ranked seventh, ahead of the United Kingdom; 10% of all smog and 9% of all particulate-related respiratory disease can be attributed to the carbon emissions of the health care industry. This breaks down to possibly 20,000 premature deaths per year.² Our current health care industry is a significant driver of environmentally related disease and will continue to be so, unless major change occurs.

Although much of it is behind the scenes, providing health care 24/7 is a highly energy-intensive and waste-producing endeavor. Many of the innovations to reduce carbon emissions that have been seen in other industries have lagged behind in health care, as we have focused on other issues.

But the health care system is transitioning. It strives to address the whole person, including where they live, work, and play. A key component of this will be addressing our impact on the environments we serve. How can we make that argument if we don’t first address our own impact on the climate?

Carbon-neutral health care

Health care is one of the few industries that has the economic clout, the scientific basis, the community engagement, and perhaps most importantly the motivations to “first, do no harm” that could lead a national (if not a global) transformation in environmental stewardship among all industries.

Many agree that action is needed, but is essential that we set specific meaningful goals that take into account the urgency of the situation. One possible solution is to encourage every health care system to begin the process of becoming carbon neutral. Simply defined, carbon neutrality is balancing the activities that result in carbon emissions with activities that reduce carbon emissions. Carbon neutrality has become the standard by which an industry’s commitment to reducing carbon emissions is measured. The measurement is standardized and achievable, and the basic concept is understood by most. It results not only in long-term benefits to climate change, but immediate improvement of air quality in the local community. In addition, achieving carbon neutrality serves as a catalyst of new desired industries, improves employee morale, and aids in recruitment.³

So, what would a carbon-neutral health care system look like? In short, sustainability should be considered in all of its actions. Risks and benefits would be contemplated, as we do with all treatments, except now environmental risks would be brought into the equation. This includes the obvious, such as purchasing and supporting the development of renewable energy, but also transportation of patients and employees, food supply chains, and even the use of virtual visits to reduce the environmental impact of patient transportation.

I am optimistic that carbon neutrality is achievable in the health care sector. It can drive economic development and engage the community in environmental stewardship efforts. But time is of the essence and leaders for these efforts are needed now. As hospitalists, we are on the front lines of the health care system. We see the direct impact of social, economic, and environmental issues on our patients. We have credibility with both our patients and hospital administration. Among all industries, there need to be champions of environmental sustainability efforts. Hospitalists are uniquely positioned to fill that role.

My concern is that 12 years is right around the corner. We are at an inflection point on our efforts to reduce carbon emissions and that is good, but time has become our enemy. The difference between terrible and unlivable will be our, and the world’s, response to reducing carbon emissions.

It is time for bold action from us, the health care community. It is our moment and our place to lead those efforts, so let’s take advantage of both this challenge and this opportunity. Consider leading those efforts in your health care system.

Dr. Conrad is medical director of community affairs and health policy at Ochsner Health Systems in New Orleans.

References

1. Special Report on Global Warming of 1.5°C. Incheon [Republic of Korea]: Intergovernmental Panel on Climate Change. 7 Oct 2018.

2. Eckelman MJ, Sherman J. Environmental Impacts of the U.S. Health Care System and Effects on Public Health. PLoS ONE. 11(6):e0157014.

3. McCunn LJ, Gifford R. Do green offices affect employee engagement and environmental attitudes? Archit Sci Rev. 55:2;128-34. doi: 10.1080/00038628.2012.667939.
 

I have always enjoyed talking with my patients from coastal Louisiana. They enjoy life, embrace their environment, and give me a perspective which is both similar and different than that of residents of New Orleans where I practice hospital medicine.

Bernhard_Staehli/Thinkstock

Their hospitalization is often a reflective moment in their lives. Lately I have been asking them about their advice to their children concerning the future of southern Louisiana in reference to sea rise, global warming, and increasing climatic events. More often than not, they have been telling their children it is time to move away.

These are a people who have strong devotion to family, but they are also practical. More than anything they would like their children to stay and preserve their heritage, but concern for their children’s future outweighs that. They have not come to this conclusion by scientific reports, but rather by what is happening before them. This group of people doesn’t alarm easily, but they see the unrelenting evidence of land loss and sea rise before them with little reason to believe it will change.

I am normally not one to speak out about climate change. Like most I have listened to the continuous alarms sounded by experts but have always assumed someone more qualified than myself should lead the efforts. But when I see the tangible effects of climate change both in my own life and the lives of my patients, I feel a sense of urgency.

12 years

Twelve years. That is the time we have to significantly reduce carbon emissions before catastrophic and potentially irreversible events will occur. This evidence is according to the authors of the landmark report by the UN Intergovernmental Panel on Climate Change released in October 2018. The report states urgent and unprecedented changes are needed to limit temperature elevations of 1.5°C and 2°C, as compared with the preindustrial era. Exceeding a 2°C elevation will likely lead to global adverse events at an unprecedented level.¹

The events forecast by the U.N. report are not abstract, particularly as they relate to public health. With high confidence, the report outlines with high specificity: increases in extreme heat, floods, crop failures, and a multitude of economic and social stressors which will affect the care of our most vulnerable patients.¹

This statement by Dr. Dana Hanson, president of the World Medical Association, summarizes the effects of climate change on the delivery of health care: “Climate change represents an inevitable massive threat to global health that will likely eclipse the major pandemics as a leading cause of death in the 21st century.”

So, what does the health care system have to do with climate change and its primary driver, carbon emissions? More than I realized, as the U.S. health care industry produces 10% of the nation’s carbon emissions.² If the U.S. health care system was a country it would be ranked seventh, ahead of the United Kingdom; 10% of all smog and 9% of all particulate-related respiratory disease can be attributed to the carbon emissions of the health care industry. This breaks down to possibly 20,000 premature deaths per year.² Our current health care industry is a significant driver of environmentally related disease and will continue to be so, unless major change occurs.

Although much of it is behind the scenes, providing health care 24/7 is a highly energy-intensive and waste-producing endeavor. Many of the innovations to reduce carbon emissions that have been seen in other industries have lagged behind in health care, as we have focused on other issues.

But the health care system is transitioning. It strives to address the whole person, including where they live, work, and play. A key component of this will be addressing our impact on the environments we serve. How can we make that argument if we don’t first address our own impact on the climate?

Carbon-neutral health care

Health care is one of the few industries that has the economic clout, the scientific basis, the community engagement, and perhaps most importantly the motivations to “first, do no harm” that could lead a national (if not a global) transformation in environmental stewardship among all industries.

Many agree that action is needed, but is essential that we set specific meaningful goals that take into account the urgency of the situation. One possible solution is to encourage every health care system to begin the process of becoming carbon neutral. Simply defined, carbon neutrality is balancing the activities that result in carbon emissions with activities that reduce carbon emissions. Carbon neutrality has become the standard by which an industry’s commitment to reducing carbon emissions is measured. The measurement is standardized and achievable, and the basic concept is understood by most. It results not only in long-term benefits to climate change, but immediate improvement of air quality in the local community. In addition, achieving carbon neutrality serves as a catalyst of new desired industries, improves employee morale, and aids in recruitment.³

So, what would a carbon-neutral health care system look like? In short, sustainability should be considered in all of its actions. Risks and benefits would be contemplated, as we do with all treatments, except now environmental risks would be brought into the equation. This includes the obvious, such as purchasing and supporting the development of renewable energy, but also transportation of patients and employees, food supply chains, and even the use of virtual visits to reduce the environmental impact of patient transportation.

I am optimistic that carbon neutrality is achievable in the health care sector. It can drive economic development and engage the community in environmental stewardship efforts. But time is of the essence and leaders for these efforts are needed now. As hospitalists, we are on the front lines of the health care system. We see the direct impact of social, economic, and environmental issues on our patients. We have credibility with both our patients and hospital administration. Among all industries, there need to be champions of environmental sustainability efforts. Hospitalists are uniquely positioned to fill that role.

My concern is that 12 years is right around the corner. We are at an inflection point on our efforts to reduce carbon emissions and that is good, but time has become our enemy. The difference between terrible and unlivable will be our, and the world’s, response to reducing carbon emissions.

It is time for bold action from us, the health care community. It is our moment and our place to lead those efforts, so let’s take advantage of both this challenge and this opportunity. Consider leading those efforts in your health care system.

Dr. Conrad is medical director of community affairs and health policy at Ochsner Health Systems in New Orleans.

References

1. Special Report on Global Warming of 1.5°C. Incheon [Republic of Korea]: Intergovernmental Panel on Climate Change. 7 Oct 2018.

2. Eckelman MJ, Sherman J. Environmental Impacts of the U.S. Health Care System and Effects on Public Health. PLoS ONE. 11(6):e0157014.

3. McCunn LJ, Gifford R. Do green offices affect employee engagement and environmental attitudes? Archit Sci Rev. 55:2;128-34. doi: 10.1080/00038628.2012.667939.
 

The programmed death-ligand 1 (PD-L1) inhibitor pembrolizumab showed manageable safety and promising clinical activity in patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to results from two early-phase studies.

The phase 1b KEYNOTE-013 study included an expansion cohort that evaluated pembrolizumab monotherapy in patients with relapsed/refractory PMBCL. Based on preliminary findings from KEYNOTE-013, the phase 2 KEYNOTE-170 study was initiated to validate these results.

Philippe Armand, MD, PhD, of Dana-Farber Cancer Institute, Boston, and colleagues reported results from 53 patients in KEYNOTE-170 and extended follow-up of 21 patients in KEYNOTE-013. Data from these two trials formed the basis of an accelerated approval by the Food and Drug Administration of pembrolizumab in patients with relapsed/refractory PMBCL in June 2018.

“Frequent amplification and translocation events occur at 9p24.1 in PMBCL, resulting in tumor expression of the programmed cell death-1 (PD-1) ligands PD-L1 and PD-L2. This suggests susceptibility of PMBCL to PD-1 blockade,” the researchers wrote in the Journal of Clinical Oncology.

KEYNOTE-170 included patients with relapsed or refractory disease who were transplant-ineligible and had failed a minimum of two prior lines of treatment. KEYNOTE-013 enrolled patients who relapsed following autologous stem cell transplantation or were ineligible for transplant.

Among patients in KEYNOTE-013 and KEYNOTE-170, the objective response rates were 48% and 45%, respectively. In total, 33% of patients in KEYNOTE-013 and 13% of patients in KEYNOTE-170 achieved a complete response. Among these patients, no disease progression was observed.

The median progression-free survival in KEYNOTE-170 was 5.5 months and 10.4 months in KEYNOTE-013. In KEYNOTE-170, median overall survival was not reached, while in KEYNOTE-013, the median overall survival was 31.4 months.

After a median follow-up time of 29.1 months in KEYNOTE-013 and 12.5 months in KEYNOTE-170, the median duration of response was not reached in either trial, the researchers reported.

With respect to safety, pembrolizumab-related grade 3 or 4 adverse events were observed in 23% and 24% of patients in KEYNOTE-170 and KEYNOTE-013, respectively. The most common adverse event in both trials was neutropenia. No deaths related to pembrolizumab were observed.

Response rates were lower in KEYNOTE-170, compared with KEYNOTE-013, but the researchers noted that longer follow-up could change these results.

“Although the small numbers allow only a tentative hypothesis, they raise the question of whether PD-1 blockade in this setting might resensitize tumors to chemotherapy, as recently suggested. If this can be further validated, it could have profound implication for the management of patients with [relapsed/refractory] PMBCL,” the researchers wrote.

The study was supported by Merck Sharp & Dohme, the Harold and Virginia Lash Foundation, the Leukemia and Lymphoma Society, and the Center for Immuno-Oncology of the Dana-Farber Cancer Institute. The authors reported financial affiliations with Merck Sharp & Dohme and several other companies.

SOURCE: Armand P et al. J Clin Oncol. 2019 Sep 10. doi: 10.1200/JCO.19.01389.

The programmed death-ligand 1 (PD-L1) inhibitor pembrolizumab showed manageable safety and promising clinical activity in patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to results from two early-phase studies.

The phase 1b KEYNOTE-013 study included an expansion cohort that evaluated pembrolizumab monotherapy in patients with relapsed/refractory PMBCL. Based on preliminary findings from KEYNOTE-013, the phase 2 KEYNOTE-170 study was initiated to validate these results.

Philippe Armand, MD, PhD, of Dana-Farber Cancer Institute, Boston, and colleagues reported results from 53 patients in KEYNOTE-170 and extended follow-up of 21 patients in KEYNOTE-013. Data from these two trials formed the basis of an accelerated approval by the Food and Drug Administration of pembrolizumab in patients with relapsed/refractory PMBCL in June 2018.

“Frequent amplification and translocation events occur at 9p24.1 in PMBCL, resulting in tumor expression of the programmed cell death-1 (PD-1) ligands PD-L1 and PD-L2. This suggests susceptibility of PMBCL to PD-1 blockade,” the researchers wrote in the Journal of Clinical Oncology.

KEYNOTE-170 included patients with relapsed or refractory disease who were transplant-ineligible and had failed a minimum of two prior lines of treatment. KEYNOTE-013 enrolled patients who relapsed following autologous stem cell transplantation or were ineligible for transplant.

Among patients in KEYNOTE-013 and KEYNOTE-170, the objective response rates were 48% and 45%, respectively. In total, 33% of patients in KEYNOTE-013 and 13% of patients in KEYNOTE-170 achieved a complete response. Among these patients, no disease progression was observed.

The median progression-free survival in KEYNOTE-170 was 5.5 months and 10.4 months in KEYNOTE-013. In KEYNOTE-170, median overall survival was not reached, while in KEYNOTE-013, the median overall survival was 31.4 months.

After a median follow-up time of 29.1 months in KEYNOTE-013 and 12.5 months in KEYNOTE-170, the median duration of response was not reached in either trial, the researchers reported.

With respect to safety, pembrolizumab-related grade 3 or 4 adverse events were observed in 23% and 24% of patients in KEYNOTE-170 and KEYNOTE-013, respectively. The most common adverse event in both trials was neutropenia. No deaths related to pembrolizumab were observed.

Response rates were lower in KEYNOTE-170, compared with KEYNOTE-013, but the researchers noted that longer follow-up could change these results.

“Although the small numbers allow only a tentative hypothesis, they raise the question of whether PD-1 blockade in this setting might resensitize tumors to chemotherapy, as recently suggested. If this can be further validated, it could have profound implication for the management of patients with [relapsed/refractory] PMBCL,” the researchers wrote.

The study was supported by Merck Sharp & Dohme, the Harold and Virginia Lash Foundation, the Leukemia and Lymphoma Society, and the Center for Immuno-Oncology of the Dana-Farber Cancer Institute. The authors reported financial affiliations with Merck Sharp & Dohme and several other companies.

SOURCE: Armand P et al. J Clin Oncol. 2019 Sep 10. doi: 10.1200/JCO.19.01389.

The programmed death-ligand 1 (PD-L1) inhibitor pembrolizumab showed manageable safety and promising clinical activity in patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to results from two early-phase studies.

The phase 1b KEYNOTE-013 study included an expansion cohort that evaluated pembrolizumab monotherapy in patients with relapsed/refractory PMBCL. Based on preliminary findings from KEYNOTE-013, the phase 2 KEYNOTE-170 study was initiated to validate these results.

Philippe Armand, MD, PhD, of Dana-Farber Cancer Institute, Boston, and colleagues reported results from 53 patients in KEYNOTE-170 and extended follow-up of 21 patients in KEYNOTE-013. Data from these two trials formed the basis of an accelerated approval by the Food and Drug Administration of pembrolizumab in patients with relapsed/refractory PMBCL in June 2018.

“Frequent amplification and translocation events occur at 9p24.1 in PMBCL, resulting in tumor expression of the programmed cell death-1 (PD-1) ligands PD-L1 and PD-L2. This suggests susceptibility of PMBCL to PD-1 blockade,” the researchers wrote in the Journal of Clinical Oncology.

KEYNOTE-170 included patients with relapsed or refractory disease who were transplant-ineligible and had failed a minimum of two prior lines of treatment. KEYNOTE-013 enrolled patients who relapsed following autologous stem cell transplantation or were ineligible for transplant.

Among patients in KEYNOTE-013 and KEYNOTE-170, the objective response rates were 48% and 45%, respectively. In total, 33% of patients in KEYNOTE-013 and 13% of patients in KEYNOTE-170 achieved a complete response. Among these patients, no disease progression was observed.

The median progression-free survival in KEYNOTE-170 was 5.5 months and 10.4 months in KEYNOTE-013. In KEYNOTE-170, median overall survival was not reached, while in KEYNOTE-013, the median overall survival was 31.4 months.

After a median follow-up time of 29.1 months in KEYNOTE-013 and 12.5 months in KEYNOTE-170, the median duration of response was not reached in either trial, the researchers reported.

With respect to safety, pembrolizumab-related grade 3 or 4 adverse events were observed in 23% and 24% of patients in KEYNOTE-170 and KEYNOTE-013, respectively. The most common adverse event in both trials was neutropenia. No deaths related to pembrolizumab were observed.

Response rates were lower in KEYNOTE-170, compared with KEYNOTE-013, but the researchers noted that longer follow-up could change these results.

“Although the small numbers allow only a tentative hypothesis, they raise the question of whether PD-1 blockade in this setting might resensitize tumors to chemotherapy, as recently suggested. If this can be further validated, it could have profound implication for the management of patients with [relapsed/refractory] PMBCL,” the researchers wrote.

The study was supported by Merck Sharp & Dohme, the Harold and Virginia Lash Foundation, the Leukemia and Lymphoma Society, and the Center for Immuno-Oncology of the Dana-Farber Cancer Institute. The authors reported financial affiliations with Merck Sharp & Dohme and several other companies.

SOURCE: Armand P et al. J Clin Oncol. 2019 Sep 10. doi: 10.1200/JCO.19.01389.

Liver abnormalities in patients with psoriatic arthritis are common and are associated with higher body mass index, more severe disease, and certain therapies, new research suggests.

Wavebreakmedia Ltd/ThinkStockPhotos.com

Patients with psoriatic arthritis (PsA) often have comorbidities such as cardiovascular disease, metabolic syndrome, inflammatory bowel disease, osteoporosis, malignancy, and ophthalmic disease, and liver disease is no exception, wrote Rattapol Pakchotanon, MD, of the department of internal medicine at Phramongkutlao Hospital and College of Medicine, Bangkok, and associates. Their report is in the Journal of Rheumatology.

In psoriasis patients, the prevalence of liver abnormalities has been 24%-36% in previous research, but research regarding liver disease in PsA has been limited.

Of 1,061 patients from the University of Toronto Psoriatic Arthritis Clinic who were included in the study, 343 (32%) had liver abnormalities, including 256 who developed a liver abnormality or disease after their first evaluation at the clinic. Liver abnormality was defined as having aspartate transaminase, alanine transaminase, or alkaline phosphatase levels 1.5 times the upper limit of normal or greater, and liver diseases included drug-induced liver injury, fatty liver, viral hepatitis, autoimmune liver disease, alcoholic liver disease, liver fibrosis, and cirrhosis.

Among the patients with PsA who developed liver abnormalities or disease after their first visit, liver abnormalities occurred after an average of 8.3 years of follow-up and at a mean age of 50.5 years. The average BMI in this group was 29.7 kg/m², and 11% of patients consumed alcohol daily. A total of 105 patients had recurrent liver abnormalities, and the rest had only one visit with an abnormality; those with transient abnormalities were significantly less likely to have evidence of liver disease (P less than .001).

The most common cause of liver disease was drug-induced hepatitis (14%) and fatty liver (13%). Alcohol-induced hepatitis occurred in 10 patients, and cirrhosis was reported in 2 patients.

In a multivariable analysis, factors found to be independently associated with liver abnormalities in PsA included BMI (odds ratio, 1.07; 95% confidence interval, 1.02-1.12; P = .007), daily alcohol intake (OR, 4.46; 95% CI, 1.30-15.28; P = .02), damaged joint count (OR, 1.04; 95% CI, 1.01-1.08; P = .01), elevated C-reactive protein (OR, 2.00; 95% CI, 1.04-3.85; P = .04), use of methotrexate or leflunomide (OR, 4.39; 95% CI, 1.67-11.54; P = .003), and use of tumor necrosis factor inhibitors (OR, 10.56; 95% CI, 3.63-30.69; P less than .0001).

“We recommend monitoring liver function tests in these high risk PsA patients,” the researchers concluded. “This is important in the management of patients with PsA as many of the therapeutic options may aggravate or even lead to liver abnormalities in this patient population.”

The study was funded in part by the Arthritis Society, the Canadian Institutes of Health Research, and the Krembil Foundation. The investigators reported that they had no conflicts of interest. Dr. Pakchotanon conducted the research while he was at the Centre for Prognosis Studies in the Rheumatic Diseases at Toronto Western Hospital.

[email protected]

SOURCE: Gladman DD et al. J Rheumatol. 2019 Oct 15. doi: 10.3899/jrheum.181312

Liver abnormalities in patients with psoriatic arthritis are common and are associated with higher body mass index, more severe disease, and certain therapies, new research suggests.

Wavebreakmedia Ltd/ThinkStockPhotos.com

Patients with psoriatic arthritis (PsA) often have comorbidities such as cardiovascular disease, metabolic syndrome, inflammatory bowel disease, osteoporosis, malignancy, and ophthalmic disease, and liver disease is no exception, wrote Rattapol Pakchotanon, MD, of the department of internal medicine at Phramongkutlao Hospital and College of Medicine, Bangkok, and associates. Their report is in the Journal of Rheumatology.

In psoriasis patients, the prevalence of liver abnormalities has been 24%-36% in previous research, but research regarding liver disease in PsA has been limited.

Of 1,061 patients from the University of Toronto Psoriatic Arthritis Clinic who were included in the study, 343 (32%) had liver abnormalities, including 256 who developed a liver abnormality or disease after their first evaluation at the clinic. Liver abnormality was defined as having aspartate transaminase, alanine transaminase, or alkaline phosphatase levels 1.5 times the upper limit of normal or greater, and liver diseases included drug-induced liver injury, fatty liver, viral hepatitis, autoimmune liver disease, alcoholic liver disease, liver fibrosis, and cirrhosis.

Among the patients with PsA who developed liver abnormalities or disease after their first visit, liver abnormalities occurred after an average of 8.3 years of follow-up and at a mean age of 50.5 years. The average BMI in this group was 29.7 kg/m², and 11% of patients consumed alcohol daily. A total of 105 patients had recurrent liver abnormalities, and the rest had only one visit with an abnormality; those with transient abnormalities were significantly less likely to have evidence of liver disease (P less than .001).

The most common cause of liver disease was drug-induced hepatitis (14%) and fatty liver (13%). Alcohol-induced hepatitis occurred in 10 patients, and cirrhosis was reported in 2 patients.

In a multivariable analysis, factors found to be independently associated with liver abnormalities in PsA included BMI (odds ratio, 1.07; 95% confidence interval, 1.02-1.12; P = .007), daily alcohol intake (OR, 4.46; 95% CI, 1.30-15.28; P = .02), damaged joint count (OR, 1.04; 95% CI, 1.01-1.08; P = .01), elevated C-reactive protein (OR, 2.00; 95% CI, 1.04-3.85; P = .04), use of methotrexate or leflunomide (OR, 4.39; 95% CI, 1.67-11.54; P = .003), and use of tumor necrosis factor inhibitors (OR, 10.56; 95% CI, 3.63-30.69; P less than .0001).

“We recommend monitoring liver function tests in these high risk PsA patients,” the researchers concluded. “This is important in the management of patients with PsA as many of the therapeutic options may aggravate or even lead to liver abnormalities in this patient population.”

The study was funded in part by the Arthritis Society, the Canadian Institutes of Health Research, and the Krembil Foundation. The investigators reported that they had no conflicts of interest. Dr. Pakchotanon conducted the research while he was at the Centre for Prognosis Studies in the Rheumatic Diseases at Toronto Western Hospital.

[email protected]

SOURCE: Gladman DD et al. J Rheumatol. 2019 Oct 15. doi: 10.3899/jrheum.181312

Liver abnormalities in patients with psoriatic arthritis are common and are associated with higher body mass index, more severe disease, and certain therapies, new research suggests.

Wavebreakmedia Ltd/ThinkStockPhotos.com

Patients with psoriatic arthritis (PsA) often have comorbidities such as cardiovascular disease, metabolic syndrome, inflammatory bowel disease, osteoporosis, malignancy, and ophthalmic disease, and liver disease is no exception, wrote Rattapol Pakchotanon, MD, of the department of internal medicine at Phramongkutlao Hospital and College of Medicine, Bangkok, and associates. Their report is in the Journal of Rheumatology.

In psoriasis patients, the prevalence of liver abnormalities has been 24%-36% in previous research, but research regarding liver disease in PsA has been limited.

Of 1,061 patients from the University of Toronto Psoriatic Arthritis Clinic who were included in the study, 343 (32%) had liver abnormalities, including 256 who developed a liver abnormality or disease after their first evaluation at the clinic. Liver abnormality was defined as having aspartate transaminase, alanine transaminase, or alkaline phosphatase levels 1.5 times the upper limit of normal or greater, and liver diseases included drug-induced liver injury, fatty liver, viral hepatitis, autoimmune liver disease, alcoholic liver disease, liver fibrosis, and cirrhosis.

Among the patients with PsA who developed liver abnormalities or disease after their first visit, liver abnormalities occurred after an average of 8.3 years of follow-up and at a mean age of 50.5 years. The average BMI in this group was 29.7 kg/m², and 11% of patients consumed alcohol daily. A total of 105 patients had recurrent liver abnormalities, and the rest had only one visit with an abnormality; those with transient abnormalities were significantly less likely to have evidence of liver disease (P less than .001).

The most common cause of liver disease was drug-induced hepatitis (14%) and fatty liver (13%). Alcohol-induced hepatitis occurred in 10 patients, and cirrhosis was reported in 2 patients.

In a multivariable analysis, factors found to be independently associated with liver abnormalities in PsA included BMI (odds ratio, 1.07; 95% confidence interval, 1.02-1.12; P = .007), daily alcohol intake (OR, 4.46; 95% CI, 1.30-15.28; P = .02), damaged joint count (OR, 1.04; 95% CI, 1.01-1.08; P = .01), elevated C-reactive protein (OR, 2.00; 95% CI, 1.04-3.85; P = .04), use of methotrexate or leflunomide (OR, 4.39; 95% CI, 1.67-11.54; P = .003), and use of tumor necrosis factor inhibitors (OR, 10.56; 95% CI, 3.63-30.69; P less than .0001).

“We recommend monitoring liver function tests in these high risk PsA patients,” the researchers concluded. “This is important in the management of patients with PsA as many of the therapeutic options may aggravate or even lead to liver abnormalities in this patient population.”

The study was funded in part by the Arthritis Society, the Canadian Institutes of Health Research, and the Krembil Foundation. The investigators reported that they had no conflicts of interest. Dr. Pakchotanon conducted the research while he was at the Centre for Prognosis Studies in the Rheumatic Diseases at Toronto Western Hospital.

[email protected]

SOURCE: Gladman DD et al. J Rheumatol. 2019 Oct 15. doi: 10.3899/jrheum.181312

The flu season is underway in the United States, and an Advisory Committee on Immunization Practices’ work group is set to assess vaccines for older adults, according to data presented at a meeting of the Centers for Disease Control and Prevention’s ACIP.

copyright Wavebreakmedia/Thinkstock

Lynette Brammer of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD) presented a surveillance update of the flu season in the United States so far. Overall, the influenza A(H3N2) viruses are predominant, although dominance varies in different regions of the country, and it is too soon to predict what strain will dominate later in the season.

“While two of the four vaccine components were updated for the Southern Hemisphere, the components selected for the 2019-2020 Northern Hemisphere vaccine, at this time, look appropriate for the season,” she said.

In other flu news, Lisa Groskopf, MD, of the NCIRD discussed the influenza work group’s plans for a meta-analysis to assess the relative benefit of different vaccines for older adults, in light of the growing variety of products available.

Currently, no preferential recommendations have been made for a specific vaccine for a particular age group. “There’s a dearth of data comparing these vaccines to one another,” said Dr. Groskopf. She added that, because vaccine effectiveness varies by season, the generalizability of effectiveness data is another challenge.

The work group’s systematic review and meta-analysis is designed to compare the high-dose inactivated influenza vaccine (HD-IIV), the adjuvanted inactivated influenza vaccine (aIIV), and the recombinant influenza vaccine (RIV). The study will include adults aged 65 years and older who receive trivalent or quadrivalent HD-IIV, aIIV, or RIV, compared with those who receive another influenza vaccine, a noninfluenza control vaccine, placebo, or no vaccine. The outcomes will include data on safety and effectiveness of the vaccines, Dr. Groskopf said.

In addition to safety and effectiveness, manufacturers such as Sanofi Pasteur continue to collect data on the success of available vaccines and develop new ones. Lee-Jah Chang, MD, of Sanofi Pasteur presented results of a noninferiority study of the company’s investigational high-dose quadrivalent influenza vaccine (QIV-HD; including two prevailing B viruses) versus the high-dose trivalent influenza vaccine (TID-HD). The study was conducted at 35 sites in the United States and included 2,670 adults aged 65 years and older.

Overall, the reactogenicity profile for patients given QIV-HD was similar to that of TID-HD, and approximately 5% of patients in the QIV group reported an immediate adverse event, Dr. Chang said. However, no related deaths or related adverse events of special interest occurred in any of the study groups.

Sanofi plans to pursue licensure of the QIV-HD vaccine, with a Center for Biologics Evaluation and Research action date of Nov. 4, 2019, said Dr. Chang. If the vaccine is licensed, it should be available for purchase by health care providers in the first quarter of 2020.

The ACIP members had no financial conflicts to disclose.

The flu season is underway in the United States, and an Advisory Committee on Immunization Practices’ work group is set to assess vaccines for older adults, according to data presented at a meeting of the Centers for Disease Control and Prevention’s ACIP.

copyright Wavebreakmedia/Thinkstock

Lynette Brammer of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD) presented a surveillance update of the flu season in the United States so far. Overall, the influenza A(H3N2) viruses are predominant, although dominance varies in different regions of the country, and it is too soon to predict what strain will dominate later in the season.

“While two of the four vaccine components were updated for the Southern Hemisphere, the components selected for the 2019-2020 Northern Hemisphere vaccine, at this time, look appropriate for the season,” she said.

In other flu news, Lisa Groskopf, MD, of the NCIRD discussed the influenza work group’s plans for a meta-analysis to assess the relative benefit of different vaccines for older adults, in light of the growing variety of products available.

Currently, no preferential recommendations have been made for a specific vaccine for a particular age group. “There’s a dearth of data comparing these vaccines to one another,” said Dr. Groskopf. She added that, because vaccine effectiveness varies by season, the generalizability of effectiveness data is another challenge.

The work group’s systematic review and meta-analysis is designed to compare the high-dose inactivated influenza vaccine (HD-IIV), the adjuvanted inactivated influenza vaccine (aIIV), and the recombinant influenza vaccine (RIV). The study will include adults aged 65 years and older who receive trivalent or quadrivalent HD-IIV, aIIV, or RIV, compared with those who receive another influenza vaccine, a noninfluenza control vaccine, placebo, or no vaccine. The outcomes will include data on safety and effectiveness of the vaccines, Dr. Groskopf said.

In addition to safety and effectiveness, manufacturers such as Sanofi Pasteur continue to collect data on the success of available vaccines and develop new ones. Lee-Jah Chang, MD, of Sanofi Pasteur presented results of a noninferiority study of the company’s investigational high-dose quadrivalent influenza vaccine (QIV-HD; including two prevailing B viruses) versus the high-dose trivalent influenza vaccine (TID-HD). The study was conducted at 35 sites in the United States and included 2,670 adults aged 65 years and older.

Overall, the reactogenicity profile for patients given QIV-HD was similar to that of TID-HD, and approximately 5% of patients in the QIV group reported an immediate adverse event, Dr. Chang said. However, no related deaths or related adverse events of special interest occurred in any of the study groups.

Sanofi plans to pursue licensure of the QIV-HD vaccine, with a Center for Biologics Evaluation and Research action date of Nov. 4, 2019, said Dr. Chang. If the vaccine is licensed, it should be available for purchase by health care providers in the first quarter of 2020.

The ACIP members had no financial conflicts to disclose.

The flu season is underway in the United States, and an Advisory Committee on Immunization Practices’ work group is set to assess vaccines for older adults, according to data presented at a meeting of the Centers for Disease Control and Prevention’s ACIP.

copyright Wavebreakmedia/Thinkstock

Lynette Brammer of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD) presented a surveillance update of the flu season in the United States so far. Overall, the influenza A(H3N2) viruses are predominant, although dominance varies in different regions of the country, and it is too soon to predict what strain will dominate later in the season.

“While two of the four vaccine components were updated for the Southern Hemisphere, the components selected for the 2019-2020 Northern Hemisphere vaccine, at this time, look appropriate for the season,” she said.

In other flu news, Lisa Groskopf, MD, of the NCIRD discussed the influenza work group’s plans for a meta-analysis to assess the relative benefit of different vaccines for older adults, in light of the growing variety of products available.

Currently, no preferential recommendations have been made for a specific vaccine for a particular age group. “There’s a dearth of data comparing these vaccines to one another,” said Dr. Groskopf. She added that, because vaccine effectiveness varies by season, the generalizability of effectiveness data is another challenge.

The work group’s systematic review and meta-analysis is designed to compare the high-dose inactivated influenza vaccine (HD-IIV), the adjuvanted inactivated influenza vaccine (aIIV), and the recombinant influenza vaccine (RIV). The study will include adults aged 65 years and older who receive trivalent or quadrivalent HD-IIV, aIIV, or RIV, compared with those who receive another influenza vaccine, a noninfluenza control vaccine, placebo, or no vaccine. The outcomes will include data on safety and effectiveness of the vaccines, Dr. Groskopf said.

In addition to safety and effectiveness, manufacturers such as Sanofi Pasteur continue to collect data on the success of available vaccines and develop new ones. Lee-Jah Chang, MD, of Sanofi Pasteur presented results of a noninferiority study of the company’s investigational high-dose quadrivalent influenza vaccine (QIV-HD; including two prevailing B viruses) versus the high-dose trivalent influenza vaccine (TID-HD). The study was conducted at 35 sites in the United States and included 2,670 adults aged 65 years and older.

Overall, the reactogenicity profile for patients given QIV-HD was similar to that of TID-HD, and approximately 5% of patients in the QIV group reported an immediate adverse event, Dr. Chang said. However, no related deaths or related adverse events of special interest occurred in any of the study groups.

Sanofi plans to pursue licensure of the QIV-HD vaccine, with a Center for Biologics Evaluation and Research action date of Nov. 4, 2019, said Dr. Chang. If the vaccine is licensed, it should be available for purchase by health care providers in the first quarter of 2020.

The ACIP members had no financial conflicts to disclose.

To the Editor:

Keratoacanthoma (KA)–type squamous cell carcinomas (SCCs) are rapidly evolving neoplasms of the epithelium that often spontaneously regress but rarely metastasize.^1,2 Keratoacanthomas are thought to ascend from the hair follicle,¹ and they clinically present as an enlarging solitary crateriform nodule with a keratin-filled center. Multiple KAs are rare²; histologically, KAs can be difficult to distinguish from conventional SCCs and are frequently treated by standard surgical excision.¹ Reactive KAs are a subtype of KA that are induced by trauma including UV exposure, electromagnetic radiation, surgical procedures, chemical peels, laser treatments, and rarely tattoos.^3-5

A 56-year-old man presented to the clinic with 3 asymptomatic enlarging papulonodules within a multicolored tattoo along the right forearm and elbow of 5 months’ duration (Figure 1). The lesions developed 1 month after the tattoo was placed and were localized to the areas of red pigment. The patient had several other tattoos. Histologic examination of the lesions revealed a well-differentiated squamous neoplasm with a crateriform invagination consistent with the superficial portion of a KA (Figures 2A–C). The specimen also revealed exogenous red pigment that was consistent with the background tattoo (Figure 2D). The patient underwent excisions of all 3 KAs, and free surgical margins were obtained.

Cipollaro¹⁰ reported the first case of a KA in a tattoo in 1973. Although there have been reports of melanoma and basal cell carcinoma occurring within tattoos, KAs and conventional SCCs are the most common cutaneous neoplasms arising in tattoos.

The pathogenesis underlying the development of malignancies in tattoos is unclear. It has been hypothesized that trauma from tattooing may play a role given the temporal relationship between tattoo placement and malignancy development.¹¹ Another theory is that tattoo pigment causes a chronic inflammatory foreign body reaction that triggers carcinogenesis.¹² Lastly, it has been postulated that tattoo pigment may alter UV light absorption in the skin that could potentially impact mutagenesis.¹¹

The most common treatment of KAs is standard surgical excision.⁴ Mohs micrographic surgery is an option if the KA is located in a cosmetically sensitive area. Although there are no reports of recurrence after excision of tattoo-related KAs, new KAs forming adjacent to a previously excised KA have been reported.¹³

Currently, tattoos are not regulated by the US Food and Drug Administration before going to market. Although many states regulate the practice of tattooing, few regulate the contents of tattoo ink, and ink is only investigated when safety issues arise.¹⁴ This case provides further evidence of an association between KAs, tattooing, and potentially carcinogenic pigments, especially in red dye, supporting the need for further research on the safety of pigment components and more regulation of tattoo ink.

To the Editor:

Keratoacanthoma (KA)–type squamous cell carcinomas (SCCs) are rapidly evolving neoplasms of the epithelium that often spontaneously regress but rarely metastasize.^1,2 Keratoacanthomas are thought to ascend from the hair follicle,¹ and they clinically present as an enlarging solitary crateriform nodule with a keratin-filled center. Multiple KAs are rare²; histologically, KAs can be difficult to distinguish from conventional SCCs and are frequently treated by standard surgical excision.¹ Reactive KAs are a subtype of KA that are induced by trauma including UV exposure, electromagnetic radiation, surgical procedures, chemical peels, laser treatments, and rarely tattoos.^3-5

A 56-year-old man presented to the clinic with 3 asymptomatic enlarging papulonodules within a multicolored tattoo along the right forearm and elbow of 5 months’ duration (Figure 1). The lesions developed 1 month after the tattoo was placed and were localized to the areas of red pigment. The patient had several other tattoos. Histologic examination of the lesions revealed a well-differentiated squamous neoplasm with a crateriform invagination consistent with the superficial portion of a KA (Figures 2A–C). The specimen also revealed exogenous red pigment that was consistent with the background tattoo (Figure 2D). The patient underwent excisions of all 3 KAs, and free surgical margins were obtained.

Cipollaro¹⁰ reported the first case of a KA in a tattoo in 1973. Although there have been reports of melanoma and basal cell carcinoma occurring within tattoos, KAs and conventional SCCs are the most common cutaneous neoplasms arising in tattoos.

The pathogenesis underlying the development of malignancies in tattoos is unclear. It has been hypothesized that trauma from tattooing may play a role given the temporal relationship between tattoo placement and malignancy development.¹¹ Another theory is that tattoo pigment causes a chronic inflammatory foreign body reaction that triggers carcinogenesis.¹² Lastly, it has been postulated that tattoo pigment may alter UV light absorption in the skin that could potentially impact mutagenesis.¹¹

The most common treatment of KAs is standard surgical excision.⁴ Mohs micrographic surgery is an option if the KA is located in a cosmetically sensitive area. Although there are no reports of recurrence after excision of tattoo-related KAs, new KAs forming adjacent to a previously excised KA have been reported.¹³

Currently, tattoos are not regulated by the US Food and Drug Administration before going to market. Although many states regulate the practice of tattooing, few regulate the contents of tattoo ink, and ink is only investigated when safety issues arise.¹⁴ This case provides further evidence of an association between KAs, tattooing, and potentially carcinogenic pigments, especially in red dye, supporting the need for further research on the safety of pigment components and more regulation of tattoo ink.

To the Editor:

Keratoacanthoma (KA)–type squamous cell carcinomas (SCCs) are rapidly evolving neoplasms of the epithelium that often spontaneously regress but rarely metastasize.^1,2 Keratoacanthomas are thought to ascend from the hair follicle,¹ and they clinically present as an enlarging solitary crateriform nodule with a keratin-filled center. Multiple KAs are rare²; histologically, KAs can be difficult to distinguish from conventional SCCs and are frequently treated by standard surgical excision.¹ Reactive KAs are a subtype of KA that are induced by trauma including UV exposure, electromagnetic radiation, surgical procedures, chemical peels, laser treatments, and rarely tattoos.^3-5

A 56-year-old man presented to the clinic with 3 asymptomatic enlarging papulonodules within a multicolored tattoo along the right forearm and elbow of 5 months’ duration (Figure 1). The lesions developed 1 month after the tattoo was placed and were localized to the areas of red pigment. The patient had several other tattoos. Histologic examination of the lesions revealed a well-differentiated squamous neoplasm with a crateriform invagination consistent with the superficial portion of a KA (Figures 2A–C). The specimen also revealed exogenous red pigment that was consistent with the background tattoo (Figure 2D). The patient underwent excisions of all 3 KAs, and free surgical margins were obtained.

Cipollaro¹⁰ reported the first case of a KA in a tattoo in 1973. Although there have been reports of melanoma and basal cell carcinoma occurring within tattoos, KAs and conventional SCCs are the most common cutaneous neoplasms arising in tattoos.

The pathogenesis underlying the development of malignancies in tattoos is unclear. It has been hypothesized that trauma from tattooing may play a role given the temporal relationship between tattoo placement and malignancy development.¹¹ Another theory is that tattoo pigment causes a chronic inflammatory foreign body reaction that triggers carcinogenesis.¹² Lastly, it has been postulated that tattoo pigment may alter UV light absorption in the skin that could potentially impact mutagenesis.¹¹

The most common treatment of KAs is standard surgical excision.⁴ Mohs micrographic surgery is an option if the KA is located in a cosmetically sensitive area. Although there are no reports of recurrence after excision of tattoo-related KAs, new KAs forming adjacent to a previously excised KA have been reported.¹³

Currently, tattoos are not regulated by the US Food and Drug Administration before going to market. Although many states regulate the practice of tattooing, few regulate the contents of tattoo ink, and ink is only investigated when safety issues arise.¹⁴ This case provides further evidence of an association between KAs, tattooing, and potentially carcinogenic pigments, especially in red dye, supporting the need for further research on the safety of pigment components and more regulation of tattoo ink.

Microbes won’t believe this shocking truth!

Pathogens can be tough little critters. Always getting into places they don’t belong, and when they get there, they can be difficult to get rid of, what with their ability to quickly evolve resistance to our best medications. If only there was some shocking new way to tackle those nasty and annoying infections.

alano design/Getty Images

Thanks to some engineers and researchers from the University of Pittsburgh, if you’ve got an infection centered on a metal implant, that shocking new treatment won’t be just a figure of speech. They ran a weak electrical current through metal dental implants infected with recurring Candida albicans infection, which damaged the cell membranes of the offending fungal pathogens but left the healthy tissue around the infection alone. That damage increased the pathogen's permeability, making it more susceptible to antimicrobial treatment.

The treatment, also known as electrochemical therapy, is great if you’ve got a recurrent infection. The dormant pathogens responsible for the recurrence, not normally susceptible to treatment, are affected by antifungals or antibiotics after the shock wakes them up. Even bacteria that have evolved drug resistance become vulnerable again after a session with Dr. Electricity.

Unfortunately, while the therapy could certainly be expanded beyond dental implants, shocking yourself when you’ve got a regular old infection probably won’t work. We know – Watt a disappointment.

Blast from the brewing past

What separates a rich Belgian ale from its paler, mass-produced American competitors? Is it the sudsy je ne sais quoi produced by squabbling Walloons and Flemings debating the fine points of the brewing arts over open tanks? Perhaps it’s the signature warm-fermented ways of Trappist monks? Is it possible les Belges have hired the unemployed Artesians who once made Olympia Beer a household name across the American West?

SerhiiBobyk/Getty Images

Wrong, wrong, and faux. In fact, Belgium’s finest brews are driven by hybrids. Yeast hybrids. Specifically, rare and unusual forms of hybrid yeasts.

Or, as Belgian researcher and world beer hero Dr. Jan Steensels of VIB-KU Leuven Center for Microbiology explains, “Think of lions and tigers making a super-baby.”

Fearlessly, Dr. Steensels and his intrepid colleagues went hunting for these exotic creatures. They found that the yeasts behind many of Belgium’s finest brews combine the DNA of the traditional, domesticated ale yeast, Saccharomyces cerevisiae, with genetic material from wild yeasts such as Saccharomyces kudriavzevii.

The result? The mighty fermentation strengths of normal beer yeasts are paired with the stress resistance and alluring aromas of feral yeasts that survived mankind’s Medieval brewing endeavors and somehow stumbled into the modern brewery for a drink.

Dr. Steensels’ team is now using its knowledge to craft more yeasty lion-tiger super-babies. We at the Bureau of LOTME look forward to hoisting a pint of this “liger” elixir. We’re certain the brew will bear the name of ligers’ greatest cinematic fan, Napoleon Dynamite, and feature the subtle undertones of tater tots.

How can mosquitoes be even more fun?

If you’re anything like the gang at LOTME, you’ve spent quite a bit of time wondering which cliché is the best fit for a less-affluent Baltimore neighborhood.

DamrongpanThongwat/thinkstock

The answer? When it rains, it pours.

We’ll explain. By definition, a less-affluent neighborhood is, well, less affluent, and that lack of affluence has many health consequences for the people who live in those neighborhoods. Today we’re focusing on everyone’s favorite winged disease vector, the mosquito.

It was already known that low-income urban neighborhoods have more mosquitoes than other neighborhoods, and now the Journal of Medical Entomology has published a survey of 13 residential blocks in Baltimore that shows low-income neighborhoods have larger mosquitoes as well.

Trapping took place in five socioeconomically diverse Baltimore neighborhoods during June and July of 2015-2017. (In case you were wondering, the researchers used BG-Sentinel traps baited with CO₂ and a 2.0-mL Octenol Lure, which would have been our choice, too). It confirmed that lower affluence correlated with larger mosquito wing size. Wing size, the investigators said in a written statement, “is an accurate proxy for body size in mosquitoes, and body size influences traits that are important to disease transmission.”

So, it seems that larger mosquitoes are more efficient at transmitting diseases, which means more dengue fever, more Zika, more chikungunya, more eastern equine encephalitis, and more West Nile virus. To extend the original cliché a bit, when it rains in Baltimore, the poor neighborhoods get the wettest.

* Correction, 10/24/19: An earlier version of this story misstated the fungal target of the electrical therapy experiment.

Jonny Hawkins

Microbes won’t believe this shocking truth!

Pathogens can be tough little critters. Always getting into places they don’t belong, and when they get there, they can be difficult to get rid of, what with their ability to quickly evolve resistance to our best medications. If only there was some shocking new way to tackle those nasty and annoying infections.

alano design/Getty Images

Thanks to some engineers and researchers from the University of Pittsburgh, if you’ve got an infection centered on a metal implant, that shocking new treatment won’t be just a figure of speech. They ran a weak electrical current through metal dental implants infected with recurring Candida albicans infection, which damaged the cell membranes of the offending fungal pathogens but left the healthy tissue around the infection alone. That damage increased the pathogen's permeability, making it more susceptible to antimicrobial treatment.

The treatment, also known as electrochemical therapy, is great if you’ve got a recurrent infection. The dormant pathogens responsible for the recurrence, not normally susceptible to treatment, are affected by antifungals or antibiotics after the shock wakes them up. Even bacteria that have evolved drug resistance become vulnerable again after a session with Dr. Electricity.

Unfortunately, while the therapy could certainly be expanded beyond dental implants, shocking yourself when you’ve got a regular old infection probably won’t work. We know – Watt a disappointment.

Blast from the brewing past

What separates a rich Belgian ale from its paler, mass-produced American competitors? Is it the sudsy je ne sais quoi produced by squabbling Walloons and Flemings debating the fine points of the brewing arts over open tanks? Perhaps it’s the signature warm-fermented ways of Trappist monks? Is it possible les Belges have hired the unemployed Artesians who once made Olympia Beer a household name across the American West?

SerhiiBobyk/Getty Images

Wrong, wrong, and faux. In fact, Belgium’s finest brews are driven by hybrids. Yeast hybrids. Specifically, rare and unusual forms of hybrid yeasts.

Or, as Belgian researcher and world beer hero Dr. Jan Steensels of VIB-KU Leuven Center for Microbiology explains, “Think of lions and tigers making a super-baby.”

Fearlessly, Dr. Steensels and his intrepid colleagues went hunting for these exotic creatures. They found that the yeasts behind many of Belgium’s finest brews combine the DNA of the traditional, domesticated ale yeast, Saccharomyces cerevisiae, with genetic material from wild yeasts such as Saccharomyces kudriavzevii.

The result? The mighty fermentation strengths of normal beer yeasts are paired with the stress resistance and alluring aromas of feral yeasts that survived mankind’s Medieval brewing endeavors and somehow stumbled into the modern brewery for a drink.

Dr. Steensels’ team is now using its knowledge to craft more yeasty lion-tiger super-babies. We at the Bureau of LOTME look forward to hoisting a pint of this “liger” elixir. We’re certain the brew will bear the name of ligers’ greatest cinematic fan, Napoleon Dynamite, and feature the subtle undertones of tater tots.

How can mosquitoes be even more fun?

If you’re anything like the gang at LOTME, you’ve spent quite a bit of time wondering which cliché is the best fit for a less-affluent Baltimore neighborhood.

DamrongpanThongwat/thinkstock

The answer? When it rains, it pours.

We’ll explain. By definition, a less-affluent neighborhood is, well, less affluent, and that lack of affluence has many health consequences for the people who live in those neighborhoods. Today we’re focusing on everyone’s favorite winged disease vector, the mosquito.

It was already known that low-income urban neighborhoods have more mosquitoes than other neighborhoods, and now the Journal of Medical Entomology has published a survey of 13 residential blocks in Baltimore that shows low-income neighborhoods have larger mosquitoes as well.

Trapping took place in five socioeconomically diverse Baltimore neighborhoods during June and July of 2015-2017. (In case you were wondering, the researchers used BG-Sentinel traps baited with CO₂ and a 2.0-mL Octenol Lure, which would have been our choice, too). It confirmed that lower affluence correlated with larger mosquito wing size. Wing size, the investigators said in a written statement, “is an accurate proxy for body size in mosquitoes, and body size influences traits that are important to disease transmission.”

So, it seems that larger mosquitoes are more efficient at transmitting diseases, which means more dengue fever, more Zika, more chikungunya, more eastern equine encephalitis, and more West Nile virus. To extend the original cliché a bit, when it rains in Baltimore, the poor neighborhoods get the wettest.

* Correction, 10/24/19: An earlier version of this story misstated the fungal target of the electrical therapy experiment.

Jonny Hawkins

Microbes won’t believe this shocking truth!

Pathogens can be tough little critters. Always getting into places they don’t belong, and when they get there, they can be difficult to get rid of, what with their ability to quickly evolve resistance to our best medications. If only there was some shocking new way to tackle those nasty and annoying infections.

alano design/Getty Images

Thanks to some engineers and researchers from the University of Pittsburgh, if you’ve got an infection centered on a metal implant, that shocking new treatment won’t be just a figure of speech. They ran a weak electrical current through metal dental implants infected with recurring Candida albicans infection, which damaged the cell membranes of the offending fungal pathogens but left the healthy tissue around the infection alone. That damage increased the pathogen's permeability, making it more susceptible to antimicrobial treatment.

The treatment, also known as electrochemical therapy, is great if you’ve got a recurrent infection. The dormant pathogens responsible for the recurrence, not normally susceptible to treatment, are affected by antifungals or antibiotics after the shock wakes them up. Even bacteria that have evolved drug resistance become vulnerable again after a session with Dr. Electricity.

Unfortunately, while the therapy could certainly be expanded beyond dental implants, shocking yourself when you’ve got a regular old infection probably won’t work. We know – Watt a disappointment.

Blast from the brewing past

What separates a rich Belgian ale from its paler, mass-produced American competitors? Is it the sudsy je ne sais quoi produced by squabbling Walloons and Flemings debating the fine points of the brewing arts over open tanks? Perhaps it’s the signature warm-fermented ways of Trappist monks? Is it possible les Belges have hired the unemployed Artesians who once made Olympia Beer a household name across the American West?

SerhiiBobyk/Getty Images

Wrong, wrong, and faux. In fact, Belgium’s finest brews are driven by hybrids. Yeast hybrids. Specifically, rare and unusual forms of hybrid yeasts.

Or, as Belgian researcher and world beer hero Dr. Jan Steensels of VIB-KU Leuven Center for Microbiology explains, “Think of lions and tigers making a super-baby.”

Fearlessly, Dr. Steensels and his intrepid colleagues went hunting for these exotic creatures. They found that the yeasts behind many of Belgium’s finest brews combine the DNA of the traditional, domesticated ale yeast, Saccharomyces cerevisiae, with genetic material from wild yeasts such as Saccharomyces kudriavzevii.

The result? The mighty fermentation strengths of normal beer yeasts are paired with the stress resistance and alluring aromas of feral yeasts that survived mankind’s Medieval brewing endeavors and somehow stumbled into the modern brewery for a drink.

Dr. Steensels’ team is now using its knowledge to craft more yeasty lion-tiger super-babies. We at the Bureau of LOTME look forward to hoisting a pint of this “liger” elixir. We’re certain the brew will bear the name of ligers’ greatest cinematic fan, Napoleon Dynamite, and feature the subtle undertones of tater tots.

How can mosquitoes be even more fun?

If you’re anything like the gang at LOTME, you’ve spent quite a bit of time wondering which cliché is the best fit for a less-affluent Baltimore neighborhood.

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The answer? When it rains, it pours.

We’ll explain. By definition, a less-affluent neighborhood is, well, less affluent, and that lack of affluence has many health consequences for the people who live in those neighborhoods. Today we’re focusing on everyone’s favorite winged disease vector, the mosquito.

It was already known that low-income urban neighborhoods have more mosquitoes than other neighborhoods, and now the Journal of Medical Entomology has published a survey of 13 residential blocks in Baltimore that shows low-income neighborhoods have larger mosquitoes as well.

Trapping took place in five socioeconomically diverse Baltimore neighborhoods during June and July of 2015-2017. (In case you were wondering, the researchers used BG-Sentinel traps baited with CO₂ and a 2.0-mL Octenol Lure, which would have been our choice, too). It confirmed that lower affluence correlated with larger mosquito wing size. Wing size, the investigators said in a written statement, “is an accurate proxy for body size in mosquitoes, and body size influences traits that are important to disease transmission.”

So, it seems that larger mosquitoes are more efficient at transmitting diseases, which means more dengue fever, more Zika, more chikungunya, more eastern equine encephalitis, and more West Nile virus. To extend the original cliché a bit, when it rains in Baltimore, the poor neighborhoods get the wettest.

* Correction, 10/24/19: An earlier version of this story misstated the fungal target of the electrical therapy experiment.

Jonny Hawkins