There is at least one aspect of “Obamacare” that my mother-in-law and I can firmly agree on: Hospitals should not get paid for frequent readmissions.

The Hospital Readmission Reduction Program (HRRP), enacted by the Centers for Medicare & Medicaid Services in 2012 with the goal of penalizing hospitals for excessive readmissions, has great face validity – and noble intentions. Does it also have a potentially disastrous downside?

On one side of the coin, the HRRP has been a remarkable success. It moved the national needle significantly on readmission rates. Yes, there are some caveats about increases in observation status patients and other shifts that could account for some of the difference, but it is fairly uncontroversial that overall, there are fewer 30-day readmissions across the country following initiation of HRRP. That is perhaps encouraging evidence of the potential positive impact that policy can make to drive changes for specific targets.

However, there is also a murkier – and more controversial – side. There have been a number of studies that have suggested reductions in readmission rates may have been associated with an increase in mortality in some patient groups. You discharge a patient and hope they won’t return to the hospital, but perhaps you should be more careful what you actually wish for.

Overall, the evidence of an association between readmissions and mortality has been complicated and conflicting. Headlines have alternately raised alarm about increased deaths and then reassured that there has been no change or perhaps even some concordant improvements in mortality. Not necessarily surprising, considering that these studies are all unavoidably of observational design and use different criteria, datasets and analytic models, which then drive their seemingly conflicting results.

An article published recently in the Journal of Hospital Medicine enters into this fray. The researchers examined the potential association between changes in rates of chronic obstructive pulmonary disease (COPD) readmissions and 30-day mortality following HRRP introduction. While the initial HRRP program and subsequent analyses included patients with heart failure, acute MI, and pneumonia, the program was extended in 2014 to include patients with COPD. So, what happened in this patient group?

Through a number of statistical gymnastics, which as a nonstatistician I am having difficulty truly wrapping my head around, the researchers seem to have found a number of important insights:

• The all-cause 30-day risk-standardized readmission rate declined from 2010 to 2017.
• The all-cause 30-day risk-standardized mortality rate increased from 2010 to 2017, and the rate of increase in mortality appears to be accelerating.
• Hospitals with higher readmission rates prior to COPD readmission penalties had a lower rate of increase in mortalities.
• Hospitals that had a larger decrease in readmission rates had a larger rate of increase in mortality.

These researchers could not evaluate data at the patient level and could not adjust for changes in disease severity. However, taken together, these findings suggest that something bad may be truly happening here.

The authors of this study also point out that the associations with increased mortality have largely been seen in patients with heart failure – and now in patients with COPD – which are both chronic diseases characterized by exacerbations, as opposed to acute MI and pneumonia, which are episodic and treatable. Perhaps in those types of disease, efforts to avoid readmissions may be more universally helpful. Maybe.

Even if it is challenging for me to adjudicate the complicated methods and results of this study, I find it concerning that there is “biological plausibility” for this association. Hospitalists know exactly how this might have happened. Have you heard of the pop-up alerts that fire in the emergency department to let the physicians know that this patient was discharged within the past 30 days? You know that alert is not meant to tell you what to do, but you just might want to consider trying to discharge them or at least place them in observation – use your clinical judgment, if you know what I mean.

Within the past decade, observation units quickly cropped up all over the country, often not staffed by hospitalists nor cardiologists, where patients with decompensated heart failure, chest pain, and/or COPD, can be given Lasix and/or nebulizer treatments – at least just enough to let them walk on back out that door without a hospital admission.

At the end of the day, whether mortality rates have truly increased in the real world, this well-intentioned program seems to have serious issues. As Ashish Jha, MD, wrote in 2018, “Right now, a high-readmission, low-mortality hospital will be penalized at 6-10 times the rate of a low-readmission, high-mortality hospital. The signal from policy makers is clear – readmissions matter a lot more than mortality – and this signal needs to stop.”

Dr. Moriates is a hospitalist, the assistant dean for health care value, and an associate professor of internal medicine at Dell Medical School at University of Texas, Austin. He is also director of implementation initiatives at Costs of Care. This article first appeared on the Hospital Leader, SHM’s official blog, at hospitalleader.org.

There is at least one aspect of “Obamacare” that my mother-in-law and I can firmly agree on: Hospitals should not get paid for frequent readmissions.

The Hospital Readmission Reduction Program (HRRP), enacted by the Centers for Medicare & Medicaid Services in 2012 with the goal of penalizing hospitals for excessive readmissions, has great face validity – and noble intentions. Does it also have a potentially disastrous downside?

On one side of the coin, the HRRP has been a remarkable success. It moved the national needle significantly on readmission rates. Yes, there are some caveats about increases in observation status patients and other shifts that could account for some of the difference, but it is fairly uncontroversial that overall, there are fewer 30-day readmissions across the country following initiation of HRRP. That is perhaps encouraging evidence of the potential positive impact that policy can make to drive changes for specific targets.

However, there is also a murkier – and more controversial – side. There have been a number of studies that have suggested reductions in readmission rates may have been associated with an increase in mortality in some patient groups. You discharge a patient and hope they won’t return to the hospital, but perhaps you should be more careful what you actually wish for.

Overall, the evidence of an association between readmissions and mortality has been complicated and conflicting. Headlines have alternately raised alarm about increased deaths and then reassured that there has been no change or perhaps even some concordant improvements in mortality. Not necessarily surprising, considering that these studies are all unavoidably of observational design and use different criteria, datasets and analytic models, which then drive their seemingly conflicting results.

An article published recently in the Journal of Hospital Medicine enters into this fray. The researchers examined the potential association between changes in rates of chronic obstructive pulmonary disease (COPD) readmissions and 30-day mortality following HRRP introduction. While the initial HRRP program and subsequent analyses included patients with heart failure, acute MI, and pneumonia, the program was extended in 2014 to include patients with COPD. So, what happened in this patient group?

Through a number of statistical gymnastics, which as a nonstatistician I am having difficulty truly wrapping my head around, the researchers seem to have found a number of important insights:

• The all-cause 30-day risk-standardized readmission rate declined from 2010 to 2017.
• The all-cause 30-day risk-standardized mortality rate increased from 2010 to 2017, and the rate of increase in mortality appears to be accelerating.
• Hospitals with higher readmission rates prior to COPD readmission penalties had a lower rate of increase in mortalities.
• Hospitals that had a larger decrease in readmission rates had a larger rate of increase in mortality.

These researchers could not evaluate data at the patient level and could not adjust for changes in disease severity. However, taken together, these findings suggest that something bad may be truly happening here.

The authors of this study also point out that the associations with increased mortality have largely been seen in patients with heart failure – and now in patients with COPD – which are both chronic diseases characterized by exacerbations, as opposed to acute MI and pneumonia, which are episodic and treatable. Perhaps in those types of disease, efforts to avoid readmissions may be more universally helpful. Maybe.

Even if it is challenging for me to adjudicate the complicated methods and results of this study, I find it concerning that there is “biological plausibility” for this association. Hospitalists know exactly how this might have happened. Have you heard of the pop-up alerts that fire in the emergency department to let the physicians know that this patient was discharged within the past 30 days? You know that alert is not meant to tell you what to do, but you just might want to consider trying to discharge them or at least place them in observation – use your clinical judgment, if you know what I mean.

Within the past decade, observation units quickly cropped up all over the country, often not staffed by hospitalists nor cardiologists, where patients with decompensated heart failure, chest pain, and/or COPD, can be given Lasix and/or nebulizer treatments – at least just enough to let them walk on back out that door without a hospital admission.

At the end of the day, whether mortality rates have truly increased in the real world, this well-intentioned program seems to have serious issues. As Ashish Jha, MD, wrote in 2018, “Right now, a high-readmission, low-mortality hospital will be penalized at 6-10 times the rate of a low-readmission, high-mortality hospital. The signal from policy makers is clear – readmissions matter a lot more than mortality – and this signal needs to stop.”

Dr. Moriates is a hospitalist, the assistant dean for health care value, and an associate professor of internal medicine at Dell Medical School at University of Texas, Austin. He is also director of implementation initiatives at Costs of Care. This article first appeared on the Hospital Leader, SHM’s official blog, at hospitalleader.org.

There is at least one aspect of “Obamacare” that my mother-in-law and I can firmly agree on: Hospitals should not get paid for frequent readmissions.

The Hospital Readmission Reduction Program (HRRP), enacted by the Centers for Medicare & Medicaid Services in 2012 with the goal of penalizing hospitals for excessive readmissions, has great face validity – and noble intentions. Does it also have a potentially disastrous downside?

On one side of the coin, the HRRP has been a remarkable success. It moved the national needle significantly on readmission rates. Yes, there are some caveats about increases in observation status patients and other shifts that could account for some of the difference, but it is fairly uncontroversial that overall, there are fewer 30-day readmissions across the country following initiation of HRRP. That is perhaps encouraging evidence of the potential positive impact that policy can make to drive changes for specific targets.

However, there is also a murkier – and more controversial – side. There have been a number of studies that have suggested reductions in readmission rates may have been associated with an increase in mortality in some patient groups. You discharge a patient and hope they won’t return to the hospital, but perhaps you should be more careful what you actually wish for.

Overall, the evidence of an association between readmissions and mortality has been complicated and conflicting. Headlines have alternately raised alarm about increased deaths and then reassured that there has been no change or perhaps even some concordant improvements in mortality. Not necessarily surprising, considering that these studies are all unavoidably of observational design and use different criteria, datasets and analytic models, which then drive their seemingly conflicting results.

An article published recently in the Journal of Hospital Medicine enters into this fray. The researchers examined the potential association between changes in rates of chronic obstructive pulmonary disease (COPD) readmissions and 30-day mortality following HRRP introduction. While the initial HRRP program and subsequent analyses included patients with heart failure, acute MI, and pneumonia, the program was extended in 2014 to include patients with COPD. So, what happened in this patient group?

Through a number of statistical gymnastics, which as a nonstatistician I am having difficulty truly wrapping my head around, the researchers seem to have found a number of important insights:

• The all-cause 30-day risk-standardized readmission rate declined from 2010 to 2017.
• The all-cause 30-day risk-standardized mortality rate increased from 2010 to 2017, and the rate of increase in mortality appears to be accelerating.
• Hospitals with higher readmission rates prior to COPD readmission penalties had a lower rate of increase in mortalities.
• Hospitals that had a larger decrease in readmission rates had a larger rate of increase in mortality.

These researchers could not evaluate data at the patient level and could not adjust for changes in disease severity. However, taken together, these findings suggest that something bad may be truly happening here.

The authors of this study also point out that the associations with increased mortality have largely been seen in patients with heart failure – and now in patients with COPD – which are both chronic diseases characterized by exacerbations, as opposed to acute MI and pneumonia, which are episodic and treatable. Perhaps in those types of disease, efforts to avoid readmissions may be more universally helpful. Maybe.

Even if it is challenging for me to adjudicate the complicated methods and results of this study, I find it concerning that there is “biological plausibility” for this association. Hospitalists know exactly how this might have happened. Have you heard of the pop-up alerts that fire in the emergency department to let the physicians know that this patient was discharged within the past 30 days? You know that alert is not meant to tell you what to do, but you just might want to consider trying to discharge them or at least place them in observation – use your clinical judgment, if you know what I mean.

Within the past decade, observation units quickly cropped up all over the country, often not staffed by hospitalists nor cardiologists, where patients with decompensated heart failure, chest pain, and/or COPD, can be given Lasix and/or nebulizer treatments – at least just enough to let them walk on back out that door without a hospital admission.

At the end of the day, whether mortality rates have truly increased in the real world, this well-intentioned program seems to have serious issues. As Ashish Jha, MD, wrote in 2018, “Right now, a high-readmission, low-mortality hospital will be penalized at 6-10 times the rate of a low-readmission, high-mortality hospital. The signal from policy makers is clear – readmissions matter a lot more than mortality – and this signal needs to stop.”

Dr. Moriates is a hospitalist, the assistant dean for health care value, and an associate professor of internal medicine at Dell Medical School at University of Texas, Austin. He is also director of implementation initiatives at Costs of Care. This article first appeared on the Hospital Leader, SHM’s official blog, at hospitalleader.org.

ATLANTA – Upadacitinib (Rinvoq), a selective Janus kinase 1 (JAK1) inhibitor, significantly improved the signs and symptoms of active ankylosing spondylitis, compared with placebo, in the randomized, placebo-controlled, phase 2/3 SELECT-AXIS 1 study.

Physical functioning and imaging measures also were improved with upadacitinib in the double-blind, multicenter study, Désirée van der Heijde, MD, PhD, reported at the annual meeting of the American College of Rheumatology.

The findings are notable because patients with ankylosing spondylitis (AS) who have an inadequate response or contraindication to NSAIDs have limited treatment options other than biologic disease-modifying antirheumatic drugs (bDMARDs). The JAK pathway has emerged as a potential therapeutic target in AS, and given its recent approval for the treatment of RA as well as ongoing studies of the agent for several other chronic immune-mediated inflammatory diseases, Dr. van der Heijde and colleagues sought to assess its efficacy and safety in bDMARD-naive patients with active AS.

Of 93 AS patients aged 18 years and older who were randomized to receive 15 mg of upadacitinib daily, 51.6% achieved the primary study endpoint of 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40) at week 14, compared with 25.5% of 94 patients who received placebo, said Dr. van der Heijde, professor of rheumatology at Leiden (the Netherlands) University Medical Center.

The effect was rapid, with a clear difference emerging between the treatment and placebo groups within 2 weeks, she noted.

Significant improvements were also seen with upadacitinib for several key secondary endpoints including change from baseline to week 14 in the Ankylosing Spondylitis Disease Activity Score, Spondyloarthritis Research Consortium of Canada MRI Spine, a 50% improvement of the initial Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50), ASAS partial remission, and Bath Ankylosing Spondylitis Functional Index.

SELECT-AXIS 1 patients were adults with a mean age of 45 years who were enrolled from 60 sites in 20 countries. All met modified New York criteria for AS based on central reading of radiographs, had a BASDAI score of at least 4, had a patient assessment of total back pain of 4 or greater on a 0-10 scale at screening and baseline, were naive to bDMARDs, and had either an inadequate response to at least two NSAIDs or an intolerance/contraindication to NSAIDs.

Most patients (70.6%) were men, and 76.5% were HLA-B27 positive. Mean symptom duration was 14-15 years, and mean disease duration was 7-8 years, Dr. van der Heijde said, adding that baseline disease characteristics were balanced between the two arms.

All randomized patients received their assigned treatment, and 95.7% completed the study through week 14, including 90 of 94 placebo group patients and 89 of 93 upadacitinib patients.

“Treatment was generally well tolerated,” she said.

The proportions of patients in the treatment and placebo groups, respectively, were similar with respect to adverse events leading to discontinuation (2.2% vs. 3.2%), serious adverse events (1.1% in each group), and infections (20.4% vs. 27.7%). No serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported. Also, no differences were seen between the groups in relevant laboratory abnormalities, and no new safety finding were observed in comparison with previous upadacitinib studies in other diseases, she noted.

Dr. van der Heijde concluded that “these results support further investigation of upadacitinib for the treatment of ankylosing spondyloarthritis.”

AbbVie, which markets upadacitinib, funded the study. Dr. van der Heijde disclosed financial relationships with AbbVie and 20 other pharmaceutical companies. Many other authors also reported financial relationships with industry, including AbbVie.

sworcester@mdedge.com

SOURCE: van der Heijde D et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2728.

ATLANTA – Upadacitinib (Rinvoq), a selective Janus kinase 1 (JAK1) inhibitor, significantly improved the signs and symptoms of active ankylosing spondylitis, compared with placebo, in the randomized, placebo-controlled, phase 2/3 SELECT-AXIS 1 study.

Physical functioning and imaging measures also were improved with upadacitinib in the double-blind, multicenter study, Désirée van der Heijde, MD, PhD, reported at the annual meeting of the American College of Rheumatology.

The findings are notable because patients with ankylosing spondylitis (AS) who have an inadequate response or contraindication to NSAIDs have limited treatment options other than biologic disease-modifying antirheumatic drugs (bDMARDs). The JAK pathway has emerged as a potential therapeutic target in AS, and given its recent approval for the treatment of RA as well as ongoing studies of the agent for several other chronic immune-mediated inflammatory diseases, Dr. van der Heijde and colleagues sought to assess its efficacy and safety in bDMARD-naive patients with active AS.

Of 93 AS patients aged 18 years and older who were randomized to receive 15 mg of upadacitinib daily, 51.6% achieved the primary study endpoint of 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40) at week 14, compared with 25.5% of 94 patients who received placebo, said Dr. van der Heijde, professor of rheumatology at Leiden (the Netherlands) University Medical Center.

The effect was rapid, with a clear difference emerging between the treatment and placebo groups within 2 weeks, she noted.

Significant improvements were also seen with upadacitinib for several key secondary endpoints including change from baseline to week 14 in the Ankylosing Spondylitis Disease Activity Score, Spondyloarthritis Research Consortium of Canada MRI Spine, a 50% improvement of the initial Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50), ASAS partial remission, and Bath Ankylosing Spondylitis Functional Index.

SELECT-AXIS 1 patients were adults with a mean age of 45 years who were enrolled from 60 sites in 20 countries. All met modified New York criteria for AS based on central reading of radiographs, had a BASDAI score of at least 4, had a patient assessment of total back pain of 4 or greater on a 0-10 scale at screening and baseline, were naive to bDMARDs, and had either an inadequate response to at least two NSAIDs or an intolerance/contraindication to NSAIDs.

Most patients (70.6%) were men, and 76.5% were HLA-B27 positive. Mean symptom duration was 14-15 years, and mean disease duration was 7-8 years, Dr. van der Heijde said, adding that baseline disease characteristics were balanced between the two arms.

All randomized patients received their assigned treatment, and 95.7% completed the study through week 14, including 90 of 94 placebo group patients and 89 of 93 upadacitinib patients.

“Treatment was generally well tolerated,” she said.

The proportions of patients in the treatment and placebo groups, respectively, were similar with respect to adverse events leading to discontinuation (2.2% vs. 3.2%), serious adverse events (1.1% in each group), and infections (20.4% vs. 27.7%). No serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported. Also, no differences were seen between the groups in relevant laboratory abnormalities, and no new safety finding were observed in comparison with previous upadacitinib studies in other diseases, she noted.

Dr. van der Heijde concluded that “these results support further investigation of upadacitinib for the treatment of ankylosing spondyloarthritis.”

AbbVie, which markets upadacitinib, funded the study. Dr. van der Heijde disclosed financial relationships with AbbVie and 20 other pharmaceutical companies. Many other authors also reported financial relationships with industry, including AbbVie.

sworcester@mdedge.com

SOURCE: van der Heijde D et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2728.

ATLANTA – Upadacitinib (Rinvoq), a selective Janus kinase 1 (JAK1) inhibitor, significantly improved the signs and symptoms of active ankylosing spondylitis, compared with placebo, in the randomized, placebo-controlled, phase 2/3 SELECT-AXIS 1 study.

Physical functioning and imaging measures also were improved with upadacitinib in the double-blind, multicenter study, Désirée van der Heijde, MD, PhD, reported at the annual meeting of the American College of Rheumatology.

The findings are notable because patients with ankylosing spondylitis (AS) who have an inadequate response or contraindication to NSAIDs have limited treatment options other than biologic disease-modifying antirheumatic drugs (bDMARDs). The JAK pathway has emerged as a potential therapeutic target in AS, and given its recent approval for the treatment of RA as well as ongoing studies of the agent for several other chronic immune-mediated inflammatory diseases, Dr. van der Heijde and colleagues sought to assess its efficacy and safety in bDMARD-naive patients with active AS.

Of 93 AS patients aged 18 years and older who were randomized to receive 15 mg of upadacitinib daily, 51.6% achieved the primary study endpoint of 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40) at week 14, compared with 25.5% of 94 patients who received placebo, said Dr. van der Heijde, professor of rheumatology at Leiden (the Netherlands) University Medical Center.

The effect was rapid, with a clear difference emerging between the treatment and placebo groups within 2 weeks, she noted.

Significant improvements were also seen with upadacitinib for several key secondary endpoints including change from baseline to week 14 in the Ankylosing Spondylitis Disease Activity Score, Spondyloarthritis Research Consortium of Canada MRI Spine, a 50% improvement of the initial Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50), ASAS partial remission, and Bath Ankylosing Spondylitis Functional Index.

SELECT-AXIS 1 patients were adults with a mean age of 45 years who were enrolled from 60 sites in 20 countries. All met modified New York criteria for AS based on central reading of radiographs, had a BASDAI score of at least 4, had a patient assessment of total back pain of 4 or greater on a 0-10 scale at screening and baseline, were naive to bDMARDs, and had either an inadequate response to at least two NSAIDs or an intolerance/contraindication to NSAIDs.

Most patients (70.6%) were men, and 76.5% were HLA-B27 positive. Mean symptom duration was 14-15 years, and mean disease duration was 7-8 years, Dr. van der Heijde said, adding that baseline disease characteristics were balanced between the two arms.

All randomized patients received their assigned treatment, and 95.7% completed the study through week 14, including 90 of 94 placebo group patients and 89 of 93 upadacitinib patients.

“Treatment was generally well tolerated,” she said.

The proportions of patients in the treatment and placebo groups, respectively, were similar with respect to adverse events leading to discontinuation (2.2% vs. 3.2%), serious adverse events (1.1% in each group), and infections (20.4% vs. 27.7%). No serious infections, herpes zoster, malignancy, venous thromboembolic events, or deaths were reported. Also, no differences were seen between the groups in relevant laboratory abnormalities, and no new safety finding were observed in comparison with previous upadacitinib studies in other diseases, she noted.

Dr. van der Heijde concluded that “these results support further investigation of upadacitinib for the treatment of ankylosing spondyloarthritis.”

AbbVie, which markets upadacitinib, funded the study. Dr. van der Heijde disclosed financial relationships with AbbVie and 20 other pharmaceutical companies. Many other authors also reported financial relationships with industry, including AbbVie.

sworcester@mdedge.com

SOURCE: van der Heijde D et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2728.

CHARLOTTE, N.C. – Most children who undergo hemispherectomy for severe, intractable epilepsy report headaches after the procedure, according to a study presented at the annual meeting of the Child Neurology Society. Patients with headache before hemispherectomy may be at risk of increased headache frequency after the procedure. The most common type of headache reported is nonmigrainous headache.

“We recommend that hemispherectomy patients be evaluated and followed closely postoperatively and questioned regarding the presence of headache,” said William Bingaman, MD, vice-chair of the neurological institute and head of the section of epilepsy surgery at the Cleveland Clinic, and colleagues. “Patients should be assessed and treated quickly to decrease prolonged pain and suffering and increase function.”

The two main types of hemispherectomy are anatomical and functional. Anatomical hemispherectomy entails the removal of a large amount of brain mass. Functional hemispherectomy entails the removal of a smaller amount of brain mass, as well as the disconnection of the brain’s hemispheres. Most patients are seizure free or have reduced seizure frequency after hemispherectomy. Other common postoperative outcomes include changes in behavior, cognition, motor function, and speech. Many studies have explored these outcomes, but few have examined the frequency of postoperative headache in children who undergo hemispherectomy.

Dr. Bingaman and colleagues retrospectively reviewed the charts of 74 children who underwent hemispherectomy at the Cleveland Clinic during the previous 5 years. They excluded 14 patients who were too young to respond for the analysis. The investigators sent the remaining 60 patients an informative letter and followed up with a 10-minute phone questionnaire about patients’ postoperative headache symptoms.

Twenty-two (36.7%) eligible patients completed the questionnaire. Thirty-eight patients could not be reached or declined to participate. Half of the 22 respondents were male. Participants’ median age at surgery was 6.5 years. The most common types of hemispherectomy were left functional (50%) and right functional (31.8%).

Nine (39.1%) of the 22 respondents had headache before surgery, and seven (31.8%) reported a family history of headache. In all, 19 (86.4%) patients had headache after surgery, and 10 (45.5%) had headaches that began after the surgery. Of the nine patients with preoperative headache, six (66.6%) had an increase in headache frequency after surgery, two (22.2%) reported no change, and one (11.1%) had decreased headache frequency. The most common type of headache reported was tension-type headache, and migraine was the second most common.

“The cause of any posthemispherectomy headache has thus far only been attributed to hydrocephalus,” wrote Dr. Bingaman and colleagues. “The tendency of headache to worsen following stresses such as illness, stroke, trauma, etc. has been studied extensively. The pathophysiology of posthemispherectomy headache can be investigated further by classifying hemispherectomy as a type of trauma or injury, which would explain the development of postoperative headache. Previous studies on posttraumatic headache have ascribed these headaches to neuroinflammation following the injury. Additionally, posthemispherectomy headache could also be due to the buildup of debris and fluid following the operation. Future hemispherectomy patients should be treated prophylactically for headache.”

The authors did not report funding for their study or declare any disclosures.

egreb@mdedge.com

SOURCE: Pandit I et al. CNS 2019. Abstract 99.

CHARLOTTE, N.C. – Most children who undergo hemispherectomy for severe, intractable epilepsy report headaches after the procedure, according to a study presented at the annual meeting of the Child Neurology Society. Patients with headache before hemispherectomy may be at risk of increased headache frequency after the procedure. The most common type of headache reported is nonmigrainous headache.

“We recommend that hemispherectomy patients be evaluated and followed closely postoperatively and questioned regarding the presence of headache,” said William Bingaman, MD, vice-chair of the neurological institute and head of the section of epilepsy surgery at the Cleveland Clinic, and colleagues. “Patients should be assessed and treated quickly to decrease prolonged pain and suffering and increase function.”

The two main types of hemispherectomy are anatomical and functional. Anatomical hemispherectomy entails the removal of a large amount of brain mass. Functional hemispherectomy entails the removal of a smaller amount of brain mass, as well as the disconnection of the brain’s hemispheres. Most patients are seizure free or have reduced seizure frequency after hemispherectomy. Other common postoperative outcomes include changes in behavior, cognition, motor function, and speech. Many studies have explored these outcomes, but few have examined the frequency of postoperative headache in children who undergo hemispherectomy.

Dr. Bingaman and colleagues retrospectively reviewed the charts of 74 children who underwent hemispherectomy at the Cleveland Clinic during the previous 5 years. They excluded 14 patients who were too young to respond for the analysis. The investigators sent the remaining 60 patients an informative letter and followed up with a 10-minute phone questionnaire about patients’ postoperative headache symptoms.

Twenty-two (36.7%) eligible patients completed the questionnaire. Thirty-eight patients could not be reached or declined to participate. Half of the 22 respondents were male. Participants’ median age at surgery was 6.5 years. The most common types of hemispherectomy were left functional (50%) and right functional (31.8%).

Nine (39.1%) of the 22 respondents had headache before surgery, and seven (31.8%) reported a family history of headache. In all, 19 (86.4%) patients had headache after surgery, and 10 (45.5%) had headaches that began after the surgery. Of the nine patients with preoperative headache, six (66.6%) had an increase in headache frequency after surgery, two (22.2%) reported no change, and one (11.1%) had decreased headache frequency. The most common type of headache reported was tension-type headache, and migraine was the second most common.

“The cause of any posthemispherectomy headache has thus far only been attributed to hydrocephalus,” wrote Dr. Bingaman and colleagues. “The tendency of headache to worsen following stresses such as illness, stroke, trauma, etc. has been studied extensively. The pathophysiology of posthemispherectomy headache can be investigated further by classifying hemispherectomy as a type of trauma or injury, which would explain the development of postoperative headache. Previous studies on posttraumatic headache have ascribed these headaches to neuroinflammation following the injury. Additionally, posthemispherectomy headache could also be due to the buildup of debris and fluid following the operation. Future hemispherectomy patients should be treated prophylactically for headache.”

The authors did not report funding for their study or declare any disclosures.

egreb@mdedge.com

SOURCE: Pandit I et al. CNS 2019. Abstract 99.

CHARLOTTE, N.C. – Most children who undergo hemispherectomy for severe, intractable epilepsy report headaches after the procedure, according to a study presented at the annual meeting of the Child Neurology Society. Patients with headache before hemispherectomy may be at risk of increased headache frequency after the procedure. The most common type of headache reported is nonmigrainous headache.

“We recommend that hemispherectomy patients be evaluated and followed closely postoperatively and questioned regarding the presence of headache,” said William Bingaman, MD, vice-chair of the neurological institute and head of the section of epilepsy surgery at the Cleveland Clinic, and colleagues. “Patients should be assessed and treated quickly to decrease prolonged pain and suffering and increase function.”

The two main types of hemispherectomy are anatomical and functional. Anatomical hemispherectomy entails the removal of a large amount of brain mass. Functional hemispherectomy entails the removal of a smaller amount of brain mass, as well as the disconnection of the brain’s hemispheres. Most patients are seizure free or have reduced seizure frequency after hemispherectomy. Other common postoperative outcomes include changes in behavior, cognition, motor function, and speech. Many studies have explored these outcomes, but few have examined the frequency of postoperative headache in children who undergo hemispherectomy.

Dr. Bingaman and colleagues retrospectively reviewed the charts of 74 children who underwent hemispherectomy at the Cleveland Clinic during the previous 5 years. They excluded 14 patients who were too young to respond for the analysis. The investigators sent the remaining 60 patients an informative letter and followed up with a 10-minute phone questionnaire about patients’ postoperative headache symptoms.

Twenty-two (36.7%) eligible patients completed the questionnaire. Thirty-eight patients could not be reached or declined to participate. Half of the 22 respondents were male. Participants’ median age at surgery was 6.5 years. The most common types of hemispherectomy were left functional (50%) and right functional (31.8%).

Nine (39.1%) of the 22 respondents had headache before surgery, and seven (31.8%) reported a family history of headache. In all, 19 (86.4%) patients had headache after surgery, and 10 (45.5%) had headaches that began after the surgery. Of the nine patients with preoperative headache, six (66.6%) had an increase in headache frequency after surgery, two (22.2%) reported no change, and one (11.1%) had decreased headache frequency. The most common type of headache reported was tension-type headache, and migraine was the second most common.

“The cause of any posthemispherectomy headache has thus far only been attributed to hydrocephalus,” wrote Dr. Bingaman and colleagues. “The tendency of headache to worsen following stresses such as illness, stroke, trauma, etc. has been studied extensively. The pathophysiology of posthemispherectomy headache can be investigated further by classifying hemispherectomy as a type of trauma or injury, which would explain the development of postoperative headache. Previous studies on posttraumatic headache have ascribed these headaches to neuroinflammation following the injury. Additionally, posthemispherectomy headache could also be due to the buildup of debris and fluid following the operation. Future hemispherectomy patients should be treated prophylactically for headache.”

The authors did not report funding for their study or declare any disclosures.

egreb@mdedge.com

SOURCE: Pandit I et al. CNS 2019. Abstract 99.

PHILADELPHIA – Out-of-hospital cardiac arrests spike with daily counts of emissions-related particulate matter – a key contributor to urban smog – and particularly affect men and people older than age 75, according to results of a nationwide Japanese study presented at the American Heart Association scientific sessions.

Thomas321/iStock/Getty Images Plus

“Short-term exposure to particulate pollutants is a potential trigger for cardiac-origin, out-of-hospital cardiac arrest [OHCA] onset in Japan,” said Sunao Kojima, MD, a professor at Kawasaki Medical School in Kurashiki, Japan.

The study used the All-Japan Utstein Registry of OHCA throughout all 47 prefectures in Japan. The analysis then applied prefecture-specific estimates of PM2.5 – particulate matter that measures 2.5 mcm in average diameter – using a time-stratified, case-crossover design. By comparison, PM2.5 is about 1/40th the diameter of human hair (approximately 100 mcm) and about 1/12th that of cedar pollen (30 mcm).

“Increased OHCAs incidence correlated with the average increase in PM2.5 concentrations over those observed 1 day before cardiac arrest,” Dr. Kojima said.

What’s noteworthy about the Utstein registry, Dr. Kojima said, is that emergency medical service personnel in Japan are not authorized to terminate resuscitation efforts, so most OHCA patients are transported to the nearest hospital and are thus counted in the registry.

From a total count of 1.4 million EMS-assessed OHCAs from 2005 through 2016, the study focused on 103,189 bystander-witnessed events from April 2011 through 2016. The analysis further divided that population into three groups: those presenting with initial ventricular fibrillation/pulseless ventricular tachycardia (20,848); those without initial VF/pulseless VT (80,110); and those with initial cardiac rhythm of unknown origin (2,231).

“The pathways linking PM2.5 exposure with OHCA remain unknown, but several mechanisms have been suspected,” Dr. Kojima said. “A major mechanism is thought to be associated with oxidative stress and systemic inflammation.”

The average daily concentration for PM2.5 was 13.9/m³ across all of Japan, Dr. Kojima said, with the highest concentrations in western Japan (16.3/m³). A 10-mcg/m³ increase in the average PM2.5 concentrations on the day of OHCA from the previous day (lag 0-1) was associated with a 1.6% increase in OHCAs (95% confidence interval, 0.1-3.1%), he said.

“Increased PM2.5 concentrations were closely associated with OHCA incidence, even when adjusted for other pollutants, such as ozone, nitrogen dioxide, sulfur dioxide, and lag 0-1,” Dr. Kojima said.

The incidence for PM2.5-related OHCA was higher for people age 75 and older and for men, during the warm season and in the central region. In the central region, the incidence increased around 6% for every 10-mcg/m³ day-to-day increase in the average PM2.5 compared to less than 1% increases in the eastern and western regions, Dr. Kojima said.

PM2.5 levels also seemed to influence outcomes depending on the origin of the OHCA, he said. Patients with VF/pulseless VT and pulseless electrical activity had better outcomes than did those with asystole. Increased PM2.5 levels were linked with lower rates of restoration of spontaneous circulation, 1-month survival, and 1-month survival with minimal neurological impairment, he said. Patients who had chest-compression-only CPR seemed to do significantly better than did those who had chest compression with rescue breathing, he said.

“There may be room for further discussion regarding the impact of performing rescue breathing in CPR and the consequent effects of short-term PM2.5 exposure on patients with cardiac origin,” he said.

Dr. Kojima has no financial relationships to disclose. The study received funding from the Japan Ministry of the Environment, Japan Society for the Promotion of Science, and Foundation for Total Health Promotion, Japan.

SOURCE: Kojima S. AHA 2019, Session FS.AOS.F1.

PHILADELPHIA – Out-of-hospital cardiac arrests spike with daily counts of emissions-related particulate matter – a key contributor to urban smog – and particularly affect men and people older than age 75, according to results of a nationwide Japanese study presented at the American Heart Association scientific sessions.

Thomas321/iStock/Getty Images Plus

“Short-term exposure to particulate pollutants is a potential trigger for cardiac-origin, out-of-hospital cardiac arrest [OHCA] onset in Japan,” said Sunao Kojima, MD, a professor at Kawasaki Medical School in Kurashiki, Japan.

The study used the All-Japan Utstein Registry of OHCA throughout all 47 prefectures in Japan. The analysis then applied prefecture-specific estimates of PM2.5 – particulate matter that measures 2.5 mcm in average diameter – using a time-stratified, case-crossover design. By comparison, PM2.5 is about 1/40th the diameter of human hair (approximately 100 mcm) and about 1/12th that of cedar pollen (30 mcm).

“Increased OHCAs incidence correlated with the average increase in PM2.5 concentrations over those observed 1 day before cardiac arrest,” Dr. Kojima said.

What’s noteworthy about the Utstein registry, Dr. Kojima said, is that emergency medical service personnel in Japan are not authorized to terminate resuscitation efforts, so most OHCA patients are transported to the nearest hospital and are thus counted in the registry.

From a total count of 1.4 million EMS-assessed OHCAs from 2005 through 2016, the study focused on 103,189 bystander-witnessed events from April 2011 through 2016. The analysis further divided that population into three groups: those presenting with initial ventricular fibrillation/pulseless ventricular tachycardia (20,848); those without initial VF/pulseless VT (80,110); and those with initial cardiac rhythm of unknown origin (2,231).

“The pathways linking PM2.5 exposure with OHCA remain unknown, but several mechanisms have been suspected,” Dr. Kojima said. “A major mechanism is thought to be associated with oxidative stress and systemic inflammation.”

The average daily concentration for PM2.5 was 13.9/m³ across all of Japan, Dr. Kojima said, with the highest concentrations in western Japan (16.3/m³). A 10-mcg/m³ increase in the average PM2.5 concentrations on the day of OHCA from the previous day (lag 0-1) was associated with a 1.6% increase in OHCAs (95% confidence interval, 0.1-3.1%), he said.

“Increased PM2.5 concentrations were closely associated with OHCA incidence, even when adjusted for other pollutants, such as ozone, nitrogen dioxide, sulfur dioxide, and lag 0-1,” Dr. Kojima said.

The incidence for PM2.5-related OHCA was higher for people age 75 and older and for men, during the warm season and in the central region. In the central region, the incidence increased around 6% for every 10-mcg/m³ day-to-day increase in the average PM2.5 compared to less than 1% increases in the eastern and western regions, Dr. Kojima said.

PM2.5 levels also seemed to influence outcomes depending on the origin of the OHCA, he said. Patients with VF/pulseless VT and pulseless electrical activity had better outcomes than did those with asystole. Increased PM2.5 levels were linked with lower rates of restoration of spontaneous circulation, 1-month survival, and 1-month survival with minimal neurological impairment, he said. Patients who had chest-compression-only CPR seemed to do significantly better than did those who had chest compression with rescue breathing, he said.

“There may be room for further discussion regarding the impact of performing rescue breathing in CPR and the consequent effects of short-term PM2.5 exposure on patients with cardiac origin,” he said.

Dr. Kojima has no financial relationships to disclose. The study received funding from the Japan Ministry of the Environment, Japan Society for the Promotion of Science, and Foundation for Total Health Promotion, Japan.

SOURCE: Kojima S. AHA 2019, Session FS.AOS.F1.

PHILADELPHIA – Out-of-hospital cardiac arrests spike with daily counts of emissions-related particulate matter – a key contributor to urban smog – and particularly affect men and people older than age 75, according to results of a nationwide Japanese study presented at the American Heart Association scientific sessions.

Thomas321/iStock/Getty Images Plus

“Short-term exposure to particulate pollutants is a potential trigger for cardiac-origin, out-of-hospital cardiac arrest [OHCA] onset in Japan,” said Sunao Kojima, MD, a professor at Kawasaki Medical School in Kurashiki, Japan.

The study used the All-Japan Utstein Registry of OHCA throughout all 47 prefectures in Japan. The analysis then applied prefecture-specific estimates of PM2.5 – particulate matter that measures 2.5 mcm in average diameter – using a time-stratified, case-crossover design. By comparison, PM2.5 is about 1/40th the diameter of human hair (approximately 100 mcm) and about 1/12th that of cedar pollen (30 mcm).

“Increased OHCAs incidence correlated with the average increase in PM2.5 concentrations over those observed 1 day before cardiac arrest,” Dr. Kojima said.

What’s noteworthy about the Utstein registry, Dr. Kojima said, is that emergency medical service personnel in Japan are not authorized to terminate resuscitation efforts, so most OHCA patients are transported to the nearest hospital and are thus counted in the registry.

From a total count of 1.4 million EMS-assessed OHCAs from 2005 through 2016, the study focused on 103,189 bystander-witnessed events from April 2011 through 2016. The analysis further divided that population into three groups: those presenting with initial ventricular fibrillation/pulseless ventricular tachycardia (20,848); those without initial VF/pulseless VT (80,110); and those with initial cardiac rhythm of unknown origin (2,231).

“The pathways linking PM2.5 exposure with OHCA remain unknown, but several mechanisms have been suspected,” Dr. Kojima said. “A major mechanism is thought to be associated with oxidative stress and systemic inflammation.”

The average daily concentration for PM2.5 was 13.9/m³ across all of Japan, Dr. Kojima said, with the highest concentrations in western Japan (16.3/m³). A 10-mcg/m³ increase in the average PM2.5 concentrations on the day of OHCA from the previous day (lag 0-1) was associated with a 1.6% increase in OHCAs (95% confidence interval, 0.1-3.1%), he said.

“Increased PM2.5 concentrations were closely associated with OHCA incidence, even when adjusted for other pollutants, such as ozone, nitrogen dioxide, sulfur dioxide, and lag 0-1,” Dr. Kojima said.

The incidence for PM2.5-related OHCA was higher for people age 75 and older and for men, during the warm season and in the central region. In the central region, the incidence increased around 6% for every 10-mcg/m³ day-to-day increase in the average PM2.5 compared to less than 1% increases in the eastern and western regions, Dr. Kojima said.

PM2.5 levels also seemed to influence outcomes depending on the origin of the OHCA, he said. Patients with VF/pulseless VT and pulseless electrical activity had better outcomes than did those with asystole. Increased PM2.5 levels were linked with lower rates of restoration of spontaneous circulation, 1-month survival, and 1-month survival with minimal neurological impairment, he said. Patients who had chest-compression-only CPR seemed to do significantly better than did those who had chest compression with rescue breathing, he said.

“There may be room for further discussion regarding the impact of performing rescue breathing in CPR and the consequent effects of short-term PM2.5 exposure on patients with cardiac origin,” he said.

Dr. Kojima has no financial relationships to disclose. The study received funding from the Japan Ministry of the Environment, Japan Society for the Promotion of Science, and Foundation for Total Health Promotion, Japan.

SOURCE: Kojima S. AHA 2019, Session FS.AOS.F1.

Loss of pancreatic E-cadherin may interfere with normal growth and maintenance of the pancreas while contributing to multiple pathological processes, based on evidence from mouse models.

In the presence of an oncogene, E-cadherin may play a pivotal role in pancreatic tumor formation, according to lead author Yoshihiro Kaneta, of Yokohama (Japan) City University in Japan, and colleagues. These findings could lead to new treatment strategies for patients with pancreatic cancer who lack E-cadherin, they noted.

Previous studies have shown that E-cadherin is involved in tissue homeostasis, although exact mechanisms vary by organ, and have remained unclear in the pancreas, the investigators explained in Cellular and Molecular Gastroenterology and Hepatology.

According to the investigators, E-cadherin expression is up-regulated in chemically induced acute pancreatitis, while in chronic pancreatitis, which is associated with an increased risk of pancreatic adenocarcinoma, E-cadherin expression is either low or absent. Other research has pointed to a link between dysregulated E-cadherin expression and cancer progression, with a loss of E-cadherin implicated in development of diffuse-type gastric cancer; however, evidence of a similar process in pancreatic cancer has not been reported, the investigators wrote.

To determine the role of E-cadherin in pancreatic function and tumor development, the investigators conducted experiments with knockout mice lacking pancreatic E-cadherin.

For the first 2 days after birth, knockout mice were similar both phenotypically and histologically to control mice. But over time, differences became apparent. Starting at day 3, control mice were comparatively larger than knockout mice, and by day 12, knockout mice began to die, with none surviving beyond day 28. Starting at day 6, histologic changes were observed in the pancreatic tissue of knockout mice, specifically, with aberrant epithelial tubules that resembled acinar-to-ductal metaplasia (ADM). Moreover, acinar cells were dilated and lacked surface expression of E-cadherin.

“These results suggested that E-cadherin was not required for pancreatic development at the embryonic stage but was required for growth and maintenance of the pancreas in the postnatal stage,” the investigators wrote.

Additional analyses revealed further differences between pancreatic tissue from knockout mice and control mice. A variety of aberrant processes were observed in knockout mice, including replacement of acini with alpha-smooth muscle actin–positive fibrotic cells, an increased number of ductal-like structures, a reduced number of amylase-positive cells, and an increased number of cytokeratin-19–positive and CD45-positive cells. Messenger RNA expression levels were also abnormal in pancreatic tissue of knockout mice, with shifts across a variety of cytokines and chemokines. These trends toward inflammation and fibrosis were described by the investigators as pancreatitis-like changes, although they observed no pancreatic intraepithelial neoplasia (PanIN), which is a precursor of pancreatic ductal adenocarcinoma.

In the presence of an oncogene, however, loss of pancreatic E-cadherin did contribute to the development of pancreatic cancer. In the presence of a Kras mutation, knockout mice began to develop PanINs and ADMs as soon as day 4. By day 7, PanINs stained partially positive for E-cadherin, showed structural abnormalities, and exhibited decreased amylase and increased cytokeratin-19. Within a similar time frame, pancreatic tissue began to adhere to the intestine, resulting in ascites and death. No metastases to other organs were observed.

Further testing showed that pancreatic stroma contained tumor cells. While DNA double-strand breaks were scarce, the investigators pointed out that chemotherapy and radiotherapy are typically responsible for DNA damage. Based on previous research linking stem cell conversion with Kras-acquired resistance, the investigators tested markers of stem cells in pancreatic tissue of knockout mice, finding that CD44, KLF4, and KLF5 were increased.

“These observations suggested that loss of E-cadherin provided tumorigenic activity to pancreatic cells and contributed to PanIN formation,” the investigators wrote.

Additional experiments with cell lines supported the above results and added further insight. Of clinical relevance, the investigators suggested that targeting Hdac1 with histone deacetylase inhibitors may be a viable treatment strategy for patients lacking pancreatic E-cadherin.

The study was funded by the Japan Society for the Promotion of Science KAKENHI grant JP17K09465 and the Yokohama City University Kamome project. The investigators declared no conflicts of interest.

SOURCE: Kaneta Y et al. Cell Mol Gastroenterol Hepatol. 2019 Sep 14. doi: 10.1016/j.jcmgh.2019.09.001.

Loss of pancreatic E-cadherin may interfere with normal growth and maintenance of the pancreas while contributing to multiple pathological processes, based on evidence from mouse models.

In the presence of an oncogene, E-cadherin may play a pivotal role in pancreatic tumor formation, according to lead author Yoshihiro Kaneta, of Yokohama (Japan) City University in Japan, and colleagues. These findings could lead to new treatment strategies for patients with pancreatic cancer who lack E-cadherin, they noted.

Previous studies have shown that E-cadherin is involved in tissue homeostasis, although exact mechanisms vary by organ, and have remained unclear in the pancreas, the investigators explained in Cellular and Molecular Gastroenterology and Hepatology.

According to the investigators, E-cadherin expression is up-regulated in chemically induced acute pancreatitis, while in chronic pancreatitis, which is associated with an increased risk of pancreatic adenocarcinoma, E-cadherin expression is either low or absent. Other research has pointed to a link between dysregulated E-cadherin expression and cancer progression, with a loss of E-cadherin implicated in development of diffuse-type gastric cancer; however, evidence of a similar process in pancreatic cancer has not been reported, the investigators wrote.

To determine the role of E-cadherin in pancreatic function and tumor development, the investigators conducted experiments with knockout mice lacking pancreatic E-cadherin.

For the first 2 days after birth, knockout mice were similar both phenotypically and histologically to control mice. But over time, differences became apparent. Starting at day 3, control mice were comparatively larger than knockout mice, and by day 12, knockout mice began to die, with none surviving beyond day 28. Starting at day 6, histologic changes were observed in the pancreatic tissue of knockout mice, specifically, with aberrant epithelial tubules that resembled acinar-to-ductal metaplasia (ADM). Moreover, acinar cells were dilated and lacked surface expression of E-cadherin.

“These results suggested that E-cadherin was not required for pancreatic development at the embryonic stage but was required for growth and maintenance of the pancreas in the postnatal stage,” the investigators wrote.

Additional analyses revealed further differences between pancreatic tissue from knockout mice and control mice. A variety of aberrant processes were observed in knockout mice, including replacement of acini with alpha-smooth muscle actin–positive fibrotic cells, an increased number of ductal-like structures, a reduced number of amylase-positive cells, and an increased number of cytokeratin-19–positive and CD45-positive cells. Messenger RNA expression levels were also abnormal in pancreatic tissue of knockout mice, with shifts across a variety of cytokines and chemokines. These trends toward inflammation and fibrosis were described by the investigators as pancreatitis-like changes, although they observed no pancreatic intraepithelial neoplasia (PanIN), which is a precursor of pancreatic ductal adenocarcinoma.

In the presence of an oncogene, however, loss of pancreatic E-cadherin did contribute to the development of pancreatic cancer. In the presence of a Kras mutation, knockout mice began to develop PanINs and ADMs as soon as day 4. By day 7, PanINs stained partially positive for E-cadherin, showed structural abnormalities, and exhibited decreased amylase and increased cytokeratin-19. Within a similar time frame, pancreatic tissue began to adhere to the intestine, resulting in ascites and death. No metastases to other organs were observed.

Further testing showed that pancreatic stroma contained tumor cells. While DNA double-strand breaks were scarce, the investigators pointed out that chemotherapy and radiotherapy are typically responsible for DNA damage. Based on previous research linking stem cell conversion with Kras-acquired resistance, the investigators tested markers of stem cells in pancreatic tissue of knockout mice, finding that CD44, KLF4, and KLF5 were increased.

“These observations suggested that loss of E-cadherin provided tumorigenic activity to pancreatic cells and contributed to PanIN formation,” the investigators wrote.

Additional experiments with cell lines supported the above results and added further insight. Of clinical relevance, the investigators suggested that targeting Hdac1 with histone deacetylase inhibitors may be a viable treatment strategy for patients lacking pancreatic E-cadherin.

The study was funded by the Japan Society for the Promotion of Science KAKENHI grant JP17K09465 and the Yokohama City University Kamome project. The investigators declared no conflicts of interest.

SOURCE: Kaneta Y et al. Cell Mol Gastroenterol Hepatol. 2019 Sep 14. doi: 10.1016/j.jcmgh.2019.09.001.

Loss of pancreatic E-cadherin may interfere with normal growth and maintenance of the pancreas while contributing to multiple pathological processes, based on evidence from mouse models.

In the presence of an oncogene, E-cadherin may play a pivotal role in pancreatic tumor formation, according to lead author Yoshihiro Kaneta, of Yokohama (Japan) City University in Japan, and colleagues. These findings could lead to new treatment strategies for patients with pancreatic cancer who lack E-cadherin, they noted.

Previous studies have shown that E-cadherin is involved in tissue homeostasis, although exact mechanisms vary by organ, and have remained unclear in the pancreas, the investigators explained in Cellular and Molecular Gastroenterology and Hepatology.

According to the investigators, E-cadherin expression is up-regulated in chemically induced acute pancreatitis, while in chronic pancreatitis, which is associated with an increased risk of pancreatic adenocarcinoma, E-cadherin expression is either low or absent. Other research has pointed to a link between dysregulated E-cadherin expression and cancer progression, with a loss of E-cadherin implicated in development of diffuse-type gastric cancer; however, evidence of a similar process in pancreatic cancer has not been reported, the investigators wrote.

To determine the role of E-cadherin in pancreatic function and tumor development, the investigators conducted experiments with knockout mice lacking pancreatic E-cadherin.

For the first 2 days after birth, knockout mice were similar both phenotypically and histologically to control mice. But over time, differences became apparent. Starting at day 3, control mice were comparatively larger than knockout mice, and by day 12, knockout mice began to die, with none surviving beyond day 28. Starting at day 6, histologic changes were observed in the pancreatic tissue of knockout mice, specifically, with aberrant epithelial tubules that resembled acinar-to-ductal metaplasia (ADM). Moreover, acinar cells were dilated and lacked surface expression of E-cadherin.

“These results suggested that E-cadherin was not required for pancreatic development at the embryonic stage but was required for growth and maintenance of the pancreas in the postnatal stage,” the investigators wrote.

Additional analyses revealed further differences between pancreatic tissue from knockout mice and control mice. A variety of aberrant processes were observed in knockout mice, including replacement of acini with alpha-smooth muscle actin–positive fibrotic cells, an increased number of ductal-like structures, a reduced number of amylase-positive cells, and an increased number of cytokeratin-19–positive and CD45-positive cells. Messenger RNA expression levels were also abnormal in pancreatic tissue of knockout mice, with shifts across a variety of cytokines and chemokines. These trends toward inflammation and fibrosis were described by the investigators as pancreatitis-like changes, although they observed no pancreatic intraepithelial neoplasia (PanIN), which is a precursor of pancreatic ductal adenocarcinoma.

In the presence of an oncogene, however, loss of pancreatic E-cadherin did contribute to the development of pancreatic cancer. In the presence of a Kras mutation, knockout mice began to develop PanINs and ADMs as soon as day 4. By day 7, PanINs stained partially positive for E-cadherin, showed structural abnormalities, and exhibited decreased amylase and increased cytokeratin-19. Within a similar time frame, pancreatic tissue began to adhere to the intestine, resulting in ascites and death. No metastases to other organs were observed.

Further testing showed that pancreatic stroma contained tumor cells. While DNA double-strand breaks were scarce, the investigators pointed out that chemotherapy and radiotherapy are typically responsible for DNA damage. Based on previous research linking stem cell conversion with Kras-acquired resistance, the investigators tested markers of stem cells in pancreatic tissue of knockout mice, finding that CD44, KLF4, and KLF5 were increased.

“These observations suggested that loss of E-cadherin provided tumorigenic activity to pancreatic cells and contributed to PanIN formation,” the investigators wrote.

Additional experiments with cell lines supported the above results and added further insight. Of clinical relevance, the investigators suggested that targeting Hdac1 with histone deacetylase inhibitors may be a viable treatment strategy for patients lacking pancreatic E-cadherin.

The study was funded by the Japan Society for the Promotion of Science KAKENHI grant JP17K09465 and the Yokohama City University Kamome project. The investigators declared no conflicts of interest.

SOURCE: Kaneta Y et al. Cell Mol Gastroenterol Hepatol. 2019 Sep 14. doi: 10.1016/j.jcmgh.2019.09.001.

SAN FRANCISCO – Transseptal catheter access for mitral valve-in-valve replacement was associated with lower mortality, compared with transapical access, and was an independent predictor of lower mortality at 1 year, in a review of 1,529 cases in the Society of Thoracic Surgeons transcatheter valve therapy registry.

Also, transcatheter mitral valve-in-valve (MViV) replacement, in general, is “preferable to redo mitral surgery and should be the standard of care for patients with failed surgical bioprosthesis who have favorable anatomy,” said lead investigator Mayra Guerrero, MD, an interventional cardiologist at the Mayo Clinic in Rochester, Minn, at the annual Transcatheter Cardiovascular Therapeutics meeting.

MViV replacement is a catheter-based alternative to a second open procedure for high-risk patients whose first surgically implanted mitral valve fails. The 30-day mortality tops 10% in most studies of redo operations, so the field’s been moving towards catheter treatment with the Edward Lifesciences Sapien 3 valve, which carries an indication for the procedure.

There’s been a lingering question, however, about whether it’s better to deliver the device through a hole in the atrial septum or the apex of the heart. The issue may now be resolved: “For the first time, we have found a statistical difference between the two access types” in favor of transseptal, Dr. Guerrero said at the meeting sponsored by the Cardiovascular Research Foundation.

The team compared outcomes from the 1,326 transseptal Sapien 3 cases in the registry with 203 cases that used the transapical approach from June 2015 and August 2019, linking cases with Centers of Medicare & Medicaid Services data to get a better idea of outcomes. Baseline characteristics were similar between the groups, but transapical cases tended to come earlier in the series because the field is also moving to the transseptal approach.

The procedures were technically successful – the primary safety endpoint – in 97.1% of transseptal and 94.6% of transapical patients. All-cause mortality at 1 year – the primary efficacy endpoint – was 15.8% transseptally and 21.7% transapically (hazard ratio, 0.67; 95% confidence interval, 0.47-0.97; P = .03).

Transapical cases were more likely to be converted to open surgery, and on multivariate analysis, transseptal access was an independent predictor of lower 1-year mortality.

There was good maintenance of valve performance and ejection fraction in both groups at 1 year, and similar improvements in heart failure symptoms and quality of life.

Transseptal 30-day mortality was 5% with an observed/expected ratio of 0.45 versus 8.1% transapical with an observed/expected ratio of 0.69.

“I don’t think any surgeon will disagree with this: If we don’t have to do another redo mitral valve operation, that’s a good thing. It’s one of the highest-risk procedures we do in cardiac surgery. To have an alternative that cuts that 30-day mortality down to 5% is very much positive. I think this clearly answers that this is the preferred therapy,” said cardiothoracic surgeon Michael Mack, MD, director of the cardiovascular service line at Baylor Scott & White Health System, Dallas.

The 1-year transseptal mortality of 16% is at least as good as transcatheter aortic valve replacement, but Dr. Mack and other panelists agreed that longer follow-up is needed to get a more complete picture of the procedure’s durability, especially as it begins to be used in patients who are at lower surgical risk.

aotto@mdedge.com

SAN FRANCISCO – Transseptal catheter access for mitral valve-in-valve replacement was associated with lower mortality, compared with transapical access, and was an independent predictor of lower mortality at 1 year, in a review of 1,529 cases in the Society of Thoracic Surgeons transcatheter valve therapy registry.

Also, transcatheter mitral valve-in-valve (MViV) replacement, in general, is “preferable to redo mitral surgery and should be the standard of care for patients with failed surgical bioprosthesis who have favorable anatomy,” said lead investigator Mayra Guerrero, MD, an interventional cardiologist at the Mayo Clinic in Rochester, Minn, at the annual Transcatheter Cardiovascular Therapeutics meeting.

MViV replacement is a catheter-based alternative to a second open procedure for high-risk patients whose first surgically implanted mitral valve fails. The 30-day mortality tops 10% in most studies of redo operations, so the field’s been moving towards catheter treatment with the Edward Lifesciences Sapien 3 valve, which carries an indication for the procedure.

There’s been a lingering question, however, about whether it’s better to deliver the device through a hole in the atrial septum or the apex of the heart. The issue may now be resolved: “For the first time, we have found a statistical difference between the two access types” in favor of transseptal, Dr. Guerrero said at the meeting sponsored by the Cardiovascular Research Foundation.

The team compared outcomes from the 1,326 transseptal Sapien 3 cases in the registry with 203 cases that used the transapical approach from June 2015 and August 2019, linking cases with Centers of Medicare & Medicaid Services data to get a better idea of outcomes. Baseline characteristics were similar between the groups, but transapical cases tended to come earlier in the series because the field is also moving to the transseptal approach.

The procedures were technically successful – the primary safety endpoint – in 97.1% of transseptal and 94.6% of transapical patients. All-cause mortality at 1 year – the primary efficacy endpoint – was 15.8% transseptally and 21.7% transapically (hazard ratio, 0.67; 95% confidence interval, 0.47-0.97; P = .03).

Transapical cases were more likely to be converted to open surgery, and on multivariate analysis, transseptal access was an independent predictor of lower 1-year mortality.

There was good maintenance of valve performance and ejection fraction in both groups at 1 year, and similar improvements in heart failure symptoms and quality of life.

Transseptal 30-day mortality was 5% with an observed/expected ratio of 0.45 versus 8.1% transapical with an observed/expected ratio of 0.69.

“I don’t think any surgeon will disagree with this: If we don’t have to do another redo mitral valve operation, that’s a good thing. It’s one of the highest-risk procedures we do in cardiac surgery. To have an alternative that cuts that 30-day mortality down to 5% is very much positive. I think this clearly answers that this is the preferred therapy,” said cardiothoracic surgeon Michael Mack, MD, director of the cardiovascular service line at Baylor Scott & White Health System, Dallas.

The 1-year transseptal mortality of 16% is at least as good as transcatheter aortic valve replacement, but Dr. Mack and other panelists agreed that longer follow-up is needed to get a more complete picture of the procedure’s durability, especially as it begins to be used in patients who are at lower surgical risk.

aotto@mdedge.com

SAN FRANCISCO – Transseptal catheter access for mitral valve-in-valve replacement was associated with lower mortality, compared with transapical access, and was an independent predictor of lower mortality at 1 year, in a review of 1,529 cases in the Society of Thoracic Surgeons transcatheter valve therapy registry.

Also, transcatheter mitral valve-in-valve (MViV) replacement, in general, is “preferable to redo mitral surgery and should be the standard of care for patients with failed surgical bioprosthesis who have favorable anatomy,” said lead investigator Mayra Guerrero, MD, an interventional cardiologist at the Mayo Clinic in Rochester, Minn, at the annual Transcatheter Cardiovascular Therapeutics meeting.

MViV replacement is a catheter-based alternative to a second open procedure for high-risk patients whose first surgically implanted mitral valve fails. The 30-day mortality tops 10% in most studies of redo operations, so the field’s been moving towards catheter treatment with the Edward Lifesciences Sapien 3 valve, which carries an indication for the procedure.

There’s been a lingering question, however, about whether it’s better to deliver the device through a hole in the atrial septum or the apex of the heart. The issue may now be resolved: “For the first time, we have found a statistical difference between the two access types” in favor of transseptal, Dr. Guerrero said at the meeting sponsored by the Cardiovascular Research Foundation.

The team compared outcomes from the 1,326 transseptal Sapien 3 cases in the registry with 203 cases that used the transapical approach from June 2015 and August 2019, linking cases with Centers of Medicare & Medicaid Services data to get a better idea of outcomes. Baseline characteristics were similar between the groups, but transapical cases tended to come earlier in the series because the field is also moving to the transseptal approach.

The procedures were technically successful – the primary safety endpoint – in 97.1% of transseptal and 94.6% of transapical patients. All-cause mortality at 1 year – the primary efficacy endpoint – was 15.8% transseptally and 21.7% transapically (hazard ratio, 0.67; 95% confidence interval, 0.47-0.97; P = .03).

Transapical cases were more likely to be converted to open surgery, and on multivariate analysis, transseptal access was an independent predictor of lower 1-year mortality.

There was good maintenance of valve performance and ejection fraction in both groups at 1 year, and similar improvements in heart failure symptoms and quality of life.

Transseptal 30-day mortality was 5% with an observed/expected ratio of 0.45 versus 8.1% transapical with an observed/expected ratio of 0.69.

“I don’t think any surgeon will disagree with this: If we don’t have to do another redo mitral valve operation, that’s a good thing. It’s one of the highest-risk procedures we do in cardiac surgery. To have an alternative that cuts that 30-day mortality down to 5% is very much positive. I think this clearly answers that this is the preferred therapy,” said cardiothoracic surgeon Michael Mack, MD, director of the cardiovascular service line at Baylor Scott & White Health System, Dallas.

The 1-year transseptal mortality of 16% is at least as good as transcatheter aortic valve replacement, but Dr. Mack and other panelists agreed that longer follow-up is needed to get a more complete picture of the procedure’s durability, especially as it begins to be used in patients who are at lower surgical risk.

aotto@mdedge.com

SAN ANTONIO – Endoscopic ultrasound-guided radiofrequency ablation is ready for a prime time proper definitive test in a randomized controlled trial for treatment of unresectable pancreatic tumors, Amaninder Dhaliwal, MD, declared at the annual meeting of the American College of Gastroenterology.

Bruce Jancin/MDedge News

He backed this assertion by presenting his meta-analysis of 13 published studies of endoscopic ultrasound radiofrequency ablation (EUS-RFA) therapy applied to 127 patients with unresectable pancreatic tumors. Most of the studies were small, single center, and prospective, with a mean 5.2 months of follow-up. Fifty-three percent of the patients had locally advanced unresectable pancreatic ductal adenocarcinoma and 30% had pancreatic neuroendocrine tumors, with a smattering of rarer pancreatic tumors making up the balance. The median lesion size was 28.2 mm. The majority of target lesions were located on the pancreatic head.

EUS-RFA is a relatively new approach to the treatment of unresectable pancreatic tumors. It’s a minimally invasive treatment strategy guided by high-quality, real-time imaging. The meta-analysis demonstrated that the technical and clinical success rates of the EUS-RFA procedures were high and the safety profile was impressive, especially compared to the widely used alternative of surgically assisted RFA, according to Dr. Dhaliwal, a gastroenterology fellow at the University of Nebraska, Omaha.

The patients collectively underwent 156 EUS-RFA procedures, with a 98% technical success rate. The pooled clinical success rate was 84.5% as defined by reduction in lesion size, symptomatic improvement, and radiologic evidence of necrosis on imaging the day following the procedure.

”Symptoms improved as early as the next day, including hypoglycemia in patients with insulinomas,” he said.

The 7-day early adverse event rate was 13.4%, with mild to moderate abdominal pain accounting for nearly three-quarters of such events. Notably, no perforations or infections occurred. Late adverse events consisted of two cases of jaundice, two cases of mild pancreatitis, one duodenal stricture, and one cystic fluid pocket.

All of the studies utilized specialized 18- or 19-gauge needle electrodes. The mean energy delivered was 30 watts.

“I think [these] data give us some hope that we can go forward with multicenter trials in patients with unresectable pancreatic cancer and benign lesions. These patients are very sick and have limited options,” Dr. Dhaliwal observed.

He reported no financial conflicts regarding his study.

bjancin@mdedge.com

SOURCE: Dhaliwal A. ACG Abstract 30.

SAN ANTONIO – Endoscopic ultrasound-guided radiofrequency ablation is ready for a prime time proper definitive test in a randomized controlled trial for treatment of unresectable pancreatic tumors, Amaninder Dhaliwal, MD, declared at the annual meeting of the American College of Gastroenterology.

Bruce Jancin/MDedge News

He backed this assertion by presenting his meta-analysis of 13 published studies of endoscopic ultrasound radiofrequency ablation (EUS-RFA) therapy applied to 127 patients with unresectable pancreatic tumors. Most of the studies were small, single center, and prospective, with a mean 5.2 months of follow-up. Fifty-three percent of the patients had locally advanced unresectable pancreatic ductal adenocarcinoma and 30% had pancreatic neuroendocrine tumors, with a smattering of rarer pancreatic tumors making up the balance. The median lesion size was 28.2 mm. The majority of target lesions were located on the pancreatic head.

EUS-RFA is a relatively new approach to the treatment of unresectable pancreatic tumors. It’s a minimally invasive treatment strategy guided by high-quality, real-time imaging. The meta-analysis demonstrated that the technical and clinical success rates of the EUS-RFA procedures were high and the safety profile was impressive, especially compared to the widely used alternative of surgically assisted RFA, according to Dr. Dhaliwal, a gastroenterology fellow at the University of Nebraska, Omaha.

The patients collectively underwent 156 EUS-RFA procedures, with a 98% technical success rate. The pooled clinical success rate was 84.5% as defined by reduction in lesion size, symptomatic improvement, and radiologic evidence of necrosis on imaging the day following the procedure.

”Symptoms improved as early as the next day, including hypoglycemia in patients with insulinomas,” he said.

The 7-day early adverse event rate was 13.4%, with mild to moderate abdominal pain accounting for nearly three-quarters of such events. Notably, no perforations or infections occurred. Late adverse events consisted of two cases of jaundice, two cases of mild pancreatitis, one duodenal stricture, and one cystic fluid pocket.

All of the studies utilized specialized 18- or 19-gauge needle electrodes. The mean energy delivered was 30 watts.

“I think [these] data give us some hope that we can go forward with multicenter trials in patients with unresectable pancreatic cancer and benign lesions. These patients are very sick and have limited options,” Dr. Dhaliwal observed.

He reported no financial conflicts regarding his study.

bjancin@mdedge.com

SOURCE: Dhaliwal A. ACG Abstract 30.

SAN ANTONIO – Endoscopic ultrasound-guided radiofrequency ablation is ready for a prime time proper definitive test in a randomized controlled trial for treatment of unresectable pancreatic tumors, Amaninder Dhaliwal, MD, declared at the annual meeting of the American College of Gastroenterology.

Bruce Jancin/MDedge News

He backed this assertion by presenting his meta-analysis of 13 published studies of endoscopic ultrasound radiofrequency ablation (EUS-RFA) therapy applied to 127 patients with unresectable pancreatic tumors. Most of the studies were small, single center, and prospective, with a mean 5.2 months of follow-up. Fifty-three percent of the patients had locally advanced unresectable pancreatic ductal adenocarcinoma and 30% had pancreatic neuroendocrine tumors, with a smattering of rarer pancreatic tumors making up the balance. The median lesion size was 28.2 mm. The majority of target lesions were located on the pancreatic head.

EUS-RFA is a relatively new approach to the treatment of unresectable pancreatic tumors. It’s a minimally invasive treatment strategy guided by high-quality, real-time imaging. The meta-analysis demonstrated that the technical and clinical success rates of the EUS-RFA procedures were high and the safety profile was impressive, especially compared to the widely used alternative of surgically assisted RFA, according to Dr. Dhaliwal, a gastroenterology fellow at the University of Nebraska, Omaha.

The patients collectively underwent 156 EUS-RFA procedures, with a 98% technical success rate. The pooled clinical success rate was 84.5% as defined by reduction in lesion size, symptomatic improvement, and radiologic evidence of necrosis on imaging the day following the procedure.

”Symptoms improved as early as the next day, including hypoglycemia in patients with insulinomas,” he said.

The 7-day early adverse event rate was 13.4%, with mild to moderate abdominal pain accounting for nearly three-quarters of such events. Notably, no perforations or infections occurred. Late adverse events consisted of two cases of jaundice, two cases of mild pancreatitis, one duodenal stricture, and one cystic fluid pocket.

All of the studies utilized specialized 18- or 19-gauge needle electrodes. The mean energy delivered was 30 watts.

“I think [these] data give us some hope that we can go forward with multicenter trials in patients with unresectable pancreatic cancer and benign lesions. These patients are very sick and have limited options,” Dr. Dhaliwal observed.

He reported no financial conflicts regarding his study.

bjancin@mdedge.com

SOURCE: Dhaliwal A. ACG Abstract 30.

Successful deep brain stimulation of the subthalamic nucleus may have unforeseen effects on the ability to swim in some patients with Parkinson’s disease, according to findings from a case series of nine patients published in Neurology.

All nine patients in the report were experienced swimmers, including two who competed in several competition-level races. They reported losing their ability to swim after successful deep brain stimulation of the subthalamic nucleus (STN-DBS) procedures. The Neurology paper focuses on three of the patients.

All of the patients achieved good to excellent motor control and cut their L-dopa dosage by impressive amounts. But they also lost the ability to coordinate limb movement when in the water, reported Daniel Waldvogel, MD, of the University of Zurich, and associates.

“All found their ability to swim came back immediately, with improved coordination of the limbs,” when stimulation was discontinued, the team noted. But soon after the stimulation ceased, their motor symptoms also rapidly returned, leading all to resume continuous stimulation.

One possible explanation is that STN-DBS does not strongly improve dopamine levels in the supplementary motor area, which controls independent limb movements.

It “may be that DBS affects the supplementary motor area (SMA) differently than levodopa. The SMA is a main output area of the basal ganglia, with connections to the primary motor cortex and the spinal cord,” wrote Dr. Waldvogel and associates. “Functionally, the SMA is thought to be crucial for facilitating independent movements of the limbs, which is a key requirement for swimming.”

Although the SMA also partly manages gait, walking was unaffected in all nine of the patients.

The authors described three patients in more detail:

• Case 1 was a 69-year-old man who was a proficient swimmer before DBS. His Unified Parkinson’s Disease Rating Scale (UPDRS) motor score on medication fell from 28 with dyskinesia before DBS to 17 after DBS, and his levodopa-equivalent dosage declined from 1,570 mg to 920 mg. The man almost drowned after he jumped into a lake and had to be rescued by another swimmer.
• Case 4 was a 59-year-old woman who was an accomplished and competitive swimmer and had been swimming up until the DBS procedure. After DBS, her UPDRS motor score on medication fell from 9 with dyskinesia to 6, and her levodopa-equivalent dosage dropped from 825 mg to 150 mg. She had good motor outcome after DBS but lost the ability to swim. “She regularly practiced swimming with her physiotherapist, but never came close to her previous level,” the authors said.
• Case 5 was a 61-year-old woman who was a competitive swimmer, including swimming across Lake Zurich, and held a lifesaving certification. Her UPDRS motor score on medication fell from 11 with dyskinesia to 9, and her levodopa-equivalent dosage decreased from 800 mg to 180 mg. After DBS, she could swim only a quarter of a kilometer and complained of “awkward posture” during her efforts.

The phenomenon has been reported just one other time by a group from the University of Western Australia. This reported patient was a 68-year-old man with a 5-year history of medication-refractory, tremor-predominant Parkinson’s. He received DBS of the posterior subthalamic area (PSA-DBS).

The patient was a dedicated lap swimmer at his local pool. When he returned to his hobby, “he quickly realized he could not propel himself adequately and that he required assistance to get to safety. In a supervised swimming situation, he was unable to float or perform freestyle, breaststroke, or back stroke. With the stimulator turned off for 30 minutes, he regained swimming ability and lost it when the stimulator was turned on.

The Australian team noted that three similar cases presented to them, but they did not discuss those cases in the paper.

Dr. Waldvogel and coauthors wrote that they might also have unreported cases in their cohort of patients with STN-DBS.

“Our cohort of patients with PD who underwent STN-DBS at the time of this retrospective study consisted of 217 patients, but we did not assess patients systematically for their swimming skills or loss thereof,” the authors said. “Until the mechanism of the reported deterioration of the ability to swim after STN-DBS is elucidated, it is crucial that we advise patients of the potential risk of drowning and the need for a carefully supervised assessment of their swimming skills before going into deep water.”

The report received no funding, and one author disclosed financial relationships with industry.

msullivan@mdedge.com

SOURCE: Waldvogel D et al Neurology. 2019 Nov 27. doi: 10.1212/WNL.0000000000008664.

Successful deep brain stimulation of the subthalamic nucleus may have unforeseen effects on the ability to swim in some patients with Parkinson’s disease, according to findings from a case series of nine patients published in Neurology.

All nine patients in the report were experienced swimmers, including two who competed in several competition-level races. They reported losing their ability to swim after successful deep brain stimulation of the subthalamic nucleus (STN-DBS) procedures. The Neurology paper focuses on three of the patients.

All of the patients achieved good to excellent motor control and cut their L-dopa dosage by impressive amounts. But they also lost the ability to coordinate limb movement when in the water, reported Daniel Waldvogel, MD, of the University of Zurich, and associates.

“All found their ability to swim came back immediately, with improved coordination of the limbs,” when stimulation was discontinued, the team noted. But soon after the stimulation ceased, their motor symptoms also rapidly returned, leading all to resume continuous stimulation.

One possible explanation is that STN-DBS does not strongly improve dopamine levels in the supplementary motor area, which controls independent limb movements.

It “may be that DBS affects the supplementary motor area (SMA) differently than levodopa. The SMA is a main output area of the basal ganglia, with connections to the primary motor cortex and the spinal cord,” wrote Dr. Waldvogel and associates. “Functionally, the SMA is thought to be crucial for facilitating independent movements of the limbs, which is a key requirement for swimming.”

Although the SMA also partly manages gait, walking was unaffected in all nine of the patients.

The authors described three patients in more detail:

• Case 1 was a 69-year-old man who was a proficient swimmer before DBS. His Unified Parkinson’s Disease Rating Scale (UPDRS) motor score on medication fell from 28 with dyskinesia before DBS to 17 after DBS, and his levodopa-equivalent dosage declined from 1,570 mg to 920 mg. The man almost drowned after he jumped into a lake and had to be rescued by another swimmer.
• Case 4 was a 59-year-old woman who was an accomplished and competitive swimmer and had been swimming up until the DBS procedure. After DBS, her UPDRS motor score on medication fell from 9 with dyskinesia to 6, and her levodopa-equivalent dosage dropped from 825 mg to 150 mg. She had good motor outcome after DBS but lost the ability to swim. “She regularly practiced swimming with her physiotherapist, but never came close to her previous level,” the authors said.
• Case 5 was a 61-year-old woman who was a competitive swimmer, including swimming across Lake Zurich, and held a lifesaving certification. Her UPDRS motor score on medication fell from 11 with dyskinesia to 9, and her levodopa-equivalent dosage decreased from 800 mg to 180 mg. After DBS, she could swim only a quarter of a kilometer and complained of “awkward posture” during her efforts.

The phenomenon has been reported just one other time by a group from the University of Western Australia. This reported patient was a 68-year-old man with a 5-year history of medication-refractory, tremor-predominant Parkinson’s. He received DBS of the posterior subthalamic area (PSA-DBS).

The patient was a dedicated lap swimmer at his local pool. When he returned to his hobby, “he quickly realized he could not propel himself adequately and that he required assistance to get to safety. In a supervised swimming situation, he was unable to float or perform freestyle, breaststroke, or back stroke. With the stimulator turned off for 30 minutes, he regained swimming ability and lost it when the stimulator was turned on.

The Australian team noted that three similar cases presented to them, but they did not discuss those cases in the paper.

Dr. Waldvogel and coauthors wrote that they might also have unreported cases in their cohort of patients with STN-DBS.

“Our cohort of patients with PD who underwent STN-DBS at the time of this retrospective study consisted of 217 patients, but we did not assess patients systematically for their swimming skills or loss thereof,” the authors said. “Until the mechanism of the reported deterioration of the ability to swim after STN-DBS is elucidated, it is crucial that we advise patients of the potential risk of drowning and the need for a carefully supervised assessment of their swimming skills before going into deep water.”

The report received no funding, and one author disclosed financial relationships with industry.

msullivan@mdedge.com

SOURCE: Waldvogel D et al Neurology. 2019 Nov 27. doi: 10.1212/WNL.0000000000008664.

Successful deep brain stimulation of the subthalamic nucleus may have unforeseen effects on the ability to swim in some patients with Parkinson’s disease, according to findings from a case series of nine patients published in Neurology.

All nine patients in the report were experienced swimmers, including two who competed in several competition-level races. They reported losing their ability to swim after successful deep brain stimulation of the subthalamic nucleus (STN-DBS) procedures. The Neurology paper focuses on three of the patients.

All of the patients achieved good to excellent motor control and cut their L-dopa dosage by impressive amounts. But they also lost the ability to coordinate limb movement when in the water, reported Daniel Waldvogel, MD, of the University of Zurich, and associates.

“All found their ability to swim came back immediately, with improved coordination of the limbs,” when stimulation was discontinued, the team noted. But soon after the stimulation ceased, their motor symptoms also rapidly returned, leading all to resume continuous stimulation.

One possible explanation is that STN-DBS does not strongly improve dopamine levels in the supplementary motor area, which controls independent limb movements.

It “may be that DBS affects the supplementary motor area (SMA) differently than levodopa. The SMA is a main output area of the basal ganglia, with connections to the primary motor cortex and the spinal cord,” wrote Dr. Waldvogel and associates. “Functionally, the SMA is thought to be crucial for facilitating independent movements of the limbs, which is a key requirement for swimming.”

Although the SMA also partly manages gait, walking was unaffected in all nine of the patients.

The authors described three patients in more detail:

• Case 1 was a 69-year-old man who was a proficient swimmer before DBS. His Unified Parkinson’s Disease Rating Scale (UPDRS) motor score on medication fell from 28 with dyskinesia before DBS to 17 after DBS, and his levodopa-equivalent dosage declined from 1,570 mg to 920 mg. The man almost drowned after he jumped into a lake and had to be rescued by another swimmer.
• Case 4 was a 59-year-old woman who was an accomplished and competitive swimmer and had been swimming up until the DBS procedure. After DBS, her UPDRS motor score on medication fell from 9 with dyskinesia to 6, and her levodopa-equivalent dosage dropped from 825 mg to 150 mg. She had good motor outcome after DBS but lost the ability to swim. “She regularly practiced swimming with her physiotherapist, but never came close to her previous level,” the authors said.
• Case 5 was a 61-year-old woman who was a competitive swimmer, including swimming across Lake Zurich, and held a lifesaving certification. Her UPDRS motor score on medication fell from 11 with dyskinesia to 9, and her levodopa-equivalent dosage decreased from 800 mg to 180 mg. After DBS, she could swim only a quarter of a kilometer and complained of “awkward posture” during her efforts.

The phenomenon has been reported just one other time by a group from the University of Western Australia. This reported patient was a 68-year-old man with a 5-year history of medication-refractory, tremor-predominant Parkinson’s. He received DBS of the posterior subthalamic area (PSA-DBS).

The patient was a dedicated lap swimmer at his local pool. When he returned to his hobby, “he quickly realized he could not propel himself adequately and that he required assistance to get to safety. In a supervised swimming situation, he was unable to float or perform freestyle, breaststroke, or back stroke. With the stimulator turned off for 30 minutes, he regained swimming ability and lost it when the stimulator was turned on.

The Australian team noted that three similar cases presented to them, but they did not discuss those cases in the paper.

Dr. Waldvogel and coauthors wrote that they might also have unreported cases in their cohort of patients with STN-DBS.

“Our cohort of patients with PD who underwent STN-DBS at the time of this retrospective study consisted of 217 patients, but we did not assess patients systematically for their swimming skills or loss thereof,” the authors said. “Until the mechanism of the reported deterioration of the ability to swim after STN-DBS is elucidated, it is crucial that we advise patients of the potential risk of drowning and the need for a carefully supervised assessment of their swimming skills before going into deep water.”

The report received no funding, and one author disclosed financial relationships with industry.

msullivan@mdedge.com

SOURCE: Waldvogel D et al Neurology. 2019 Nov 27. doi: 10.1212/WNL.0000000000008664.

Key clinical point: Little is known about what factors predict the progression of cognitive impairment (CI) and progression after a diagnosis of multiple sclerosis (MS).

Major finding: Twenty-two percent of patients had CI at baseline in newly diagnosed MS patients. At follow-up, only 14% of patients had CI. Cognitive changes within 1 year of follow-up could not be determined by baseline characteristics or initiation of treatment.

Study details: Demographic, clinical, and conventional MRI markers at baseline were investigated for CI and changes in 1,123 patients from a multicenter cohort study.

Disclosures: “The German National MS cohort and KKNMS are supported by grants from the German Federal Ministry for Education and Research.” Several study investigators reported received financial support and grants from pharmaceutical agencies.

Citation: Johnen A, et al. J Neurol. 2019 Feb;266(2):386-397. doi: 10.1007/s00415-018-9142-y.

Key clinical point: Little is known about what factors predict the progression of cognitive impairment (CI) and progression after a diagnosis of multiple sclerosis (MS).

Major finding: Twenty-two percent of patients had CI at baseline in newly diagnosed MS patients. At follow-up, only 14% of patients had CI. Cognitive changes within 1 year of follow-up could not be determined by baseline characteristics or initiation of treatment.

Study details: Demographic, clinical, and conventional MRI markers at baseline were investigated for CI and changes in 1,123 patients from a multicenter cohort study.

Disclosures: “The German National MS cohort and KKNMS are supported by grants from the German Federal Ministry for Education and Research.” Several study investigators reported received financial support and grants from pharmaceutical agencies.

Citation: Johnen A, et al. J Neurol. 2019 Feb;266(2):386-397. doi: 10.1007/s00415-018-9142-y.

Key clinical point: Little is known about what factors predict the progression of cognitive impairment (CI) and progression after a diagnosis of multiple sclerosis (MS).

Major finding: Twenty-two percent of patients had CI at baseline in newly diagnosed MS patients. At follow-up, only 14% of patients had CI. Cognitive changes within 1 year of follow-up could not be determined by baseline characteristics or initiation of treatment.

Study details: Demographic, clinical, and conventional MRI markers at baseline were investigated for CI and changes in 1,123 patients from a multicenter cohort study.

Disclosures: “The German National MS cohort and KKNMS are supported by grants from the German Federal Ministry for Education and Research.” Several study investigators reported received financial support and grants from pharmaceutical agencies.

Citation: Johnen A, et al. J Neurol. 2019 Feb;266(2):386-397. doi: 10.1007/s00415-018-9142-y.

Key clinical point: Better management and treatment of diabetes and anxiety in MS patients may help improve cognition.

Major finding: Of 111 patients with relapsing remitting MS (majority were women with a mean age of 50 years), 22.7% had hypertension, 10.8% had diabetes, 9.9% had depression, and 9.9% had anxiety disorders.

Study details: Patients completed a psychiatric interview, a comorbidity questionnaire, and cognitive testing. Scores were converted to age-, sex-, and education-adjusted z-scores. Links between diabetes and hypertension and the cognitive z-scores were evaluated.

Disclosures: Authors disclosed receiving research support from various organizations. One author has conducted clinical trials for Biogen Idec and Rouche. Another has served as a consultant for several pharmaceutical companies, and has also received research grants and served on speaker’s bureaus for the industry.

Citation: Marrie, RA, et al.. Mult Scler Relat Disord. 2019 Jan;27:164-170. doi: 10.1016/j.msard.2018.10.018.

Key clinical point: Better management and treatment of diabetes and anxiety in MS patients may help improve cognition.

Major finding: Of 111 patients with relapsing remitting MS (majority were women with a mean age of 50 years), 22.7% had hypertension, 10.8% had diabetes, 9.9% had depression, and 9.9% had anxiety disorders.

Study details: Patients completed a psychiatric interview, a comorbidity questionnaire, and cognitive testing. Scores were converted to age-, sex-, and education-adjusted z-scores. Links between diabetes and hypertension and the cognitive z-scores were evaluated.

Disclosures: Authors disclosed receiving research support from various organizations. One author has conducted clinical trials for Biogen Idec and Rouche. Another has served as a consultant for several pharmaceutical companies, and has also received research grants and served on speaker’s bureaus for the industry.

Citation: Marrie, RA, et al.. Mult Scler Relat Disord. 2019 Jan;27:164-170. doi: 10.1016/j.msard.2018.10.018.

Key clinical point: Better management and treatment of diabetes and anxiety in MS patients may help improve cognition.

Major finding: Of 111 patients with relapsing remitting MS (majority were women with a mean age of 50 years), 22.7% had hypertension, 10.8% had diabetes, 9.9% had depression, and 9.9% had anxiety disorders.

Study details: Patients completed a psychiatric interview, a comorbidity questionnaire, and cognitive testing. Scores were converted to age-, sex-, and education-adjusted z-scores. Links between diabetes and hypertension and the cognitive z-scores were evaluated.

Disclosures: Authors disclosed receiving research support from various organizations. One author has conducted clinical trials for Biogen Idec and Rouche. Another has served as a consultant for several pharmaceutical companies, and has also received research grants and served on speaker’s bureaus for the industry.

Citation: Marrie, RA, et al.. Mult Scler Relat Disord. 2019 Jan;27:164-170. doi: 10.1016/j.msard.2018.10.018.