Recruitment is under way for 10 hospitals to participate in a one-year mentored-implementation program related to opioid monitoring. SHM will be assigning two mentors to guide them through:

• Needs assessment
• Formal selection of data collection measures
• Data collection
• The implementation of key interventions to enhance safety for patients in the hospital who are prescribed opioid medications

The program will include monthly calls, a site visit with the SHM mentors, and a formal assessment of program implementation. Is your hospital interested in participating? Visit www.hospitalmedicine.org/RADEO to learn more and complete the form.

Recruitment is under way for 10 hospitals to participate in a one-year mentored-implementation program related to opioid monitoring. SHM will be assigning two mentors to guide them through:

• Needs assessment
• Formal selection of data collection measures
• Data collection
• The implementation of key interventions to enhance safety for patients in the hospital who are prescribed opioid medications

The program will include monthly calls, a site visit with the SHM mentors, and a formal assessment of program implementation. Is your hospital interested in participating? Visit www.hospitalmedicine.org/RADEO to learn more and complete the form.

Recruitment is under way for 10 hospitals to participate in a one-year mentored-implementation program related to opioid monitoring. SHM will be assigning two mentors to guide them through:

• Needs assessment
• Formal selection of data collection measures
• Data collection
• The implementation of key interventions to enhance safety for patients in the hospital who are prescribed opioid medications

The program will include monthly calls, a site visit with the SHM mentors, and a formal assessment of program implementation. Is your hospital interested in participating? Visit www.hospitalmedicine.org/RADEO to learn more and complete the form.

Results of a large study suggest most patients taking warfarin long-term do not maintain stable international normalized ratio (INR) values.

Researchers analyzed data from more than 3700 patients and found that 74% did not have stable INRs during the first 6 months of analysis.

Of the patients who did have stable INRs during this period, only 34% maintained stable INRs over the subsequent year.

Sean D. Pokorney, MD, of Duke University Medical Center in Durham, North Carolina, and his colleagues reported these findings in JAMA.

The researchers analyzed data from a prospective registry of patients with atrial fibrillation treated at 176 clinics. The patients were enrolled from June 2010 through August 2011 and followed for 3 years through November 2014.

Patients receiving warfarin at study entry with 3 or more INR values in the first 6 months and 6 or more in the subsequent year were included.

Of 10,132 registry patients, 6383 were not taking warfarin or had insufficient INR values and were excluded.

So there were 3749 eligible patients taking warfarin. Their average age was 75. Forty-three percent of patients were female, and 91% self-identified as white.

The patients’ median time from their first warfarin prescription to baseline was 3.9 years (range, 1.5-7.5 years). Thirty-seven percent of patients were also taking aspirin, and 5% were taking clopidogrel.

Results

INR stability was defined as 80% or more INRs in the therapeutic range (2.0-3.0).

Twenty-six percent of the patients met this definition during the first 6 months, and 34% of these patients maintained stable INRs over the subsequent year.

Ten percent of all patients had 100% of their INR values in the therapeutic range during the first 6 months. Of these patients, 37% met the definition of stability over the subsequent year.

Of the patients who had 80% or more of their INR values in the therapeutic range at baseline, 36% had 1 or more well-out-of-range INRs in the following year.

Of the patients with 100% of their baseline INR values in the therapeutic range, 33% had 1 or more well-out-of-range INRs in the subsequent year.

The researchers said these results suggest warfarin stability is difficult to predict, and this study challenges the notion that patients who have done well taking warfarin should continue taking warfarin.

Results of a large study suggest most patients taking warfarin long-term do not maintain stable international normalized ratio (INR) values.

Researchers analyzed data from more than 3700 patients and found that 74% did not have stable INRs during the first 6 months of analysis.

Of the patients who did have stable INRs during this period, only 34% maintained stable INRs over the subsequent year.

Sean D. Pokorney, MD, of Duke University Medical Center in Durham, North Carolina, and his colleagues reported these findings in JAMA.

The researchers analyzed data from a prospective registry of patients with atrial fibrillation treated at 176 clinics. The patients were enrolled from June 2010 through August 2011 and followed for 3 years through November 2014.

Patients receiving warfarin at study entry with 3 or more INR values in the first 6 months and 6 or more in the subsequent year were included.

Of 10,132 registry patients, 6383 were not taking warfarin or had insufficient INR values and were excluded.

So there were 3749 eligible patients taking warfarin. Their average age was 75. Forty-three percent of patients were female, and 91% self-identified as white.

The patients’ median time from their first warfarin prescription to baseline was 3.9 years (range, 1.5-7.5 years). Thirty-seven percent of patients were also taking aspirin, and 5% were taking clopidogrel.

Results

INR stability was defined as 80% or more INRs in the therapeutic range (2.0-3.0).

Twenty-six percent of the patients met this definition during the first 6 months, and 34% of these patients maintained stable INRs over the subsequent year.

Ten percent of all patients had 100% of their INR values in the therapeutic range during the first 6 months. Of these patients, 37% met the definition of stability over the subsequent year.

Of the patients who had 80% or more of their INR values in the therapeutic range at baseline, 36% had 1 or more well-out-of-range INRs in the following year.

Of the patients with 100% of their baseline INR values in the therapeutic range, 33% had 1 or more well-out-of-range INRs in the subsequent year.

The researchers said these results suggest warfarin stability is difficult to predict, and this study challenges the notion that patients who have done well taking warfarin should continue taking warfarin.

Results of a large study suggest most patients taking warfarin long-term do not maintain stable international normalized ratio (INR) values.

Researchers analyzed data from more than 3700 patients and found that 74% did not have stable INRs during the first 6 months of analysis.

Of the patients who did have stable INRs during this period, only 34% maintained stable INRs over the subsequent year.

Sean D. Pokorney, MD, of Duke University Medical Center in Durham, North Carolina, and his colleagues reported these findings in JAMA.

The researchers analyzed data from a prospective registry of patients with atrial fibrillation treated at 176 clinics. The patients were enrolled from June 2010 through August 2011 and followed for 3 years through November 2014.

Patients receiving warfarin at study entry with 3 or more INR values in the first 6 months and 6 or more in the subsequent year were included.

Of 10,132 registry patients, 6383 were not taking warfarin or had insufficient INR values and were excluded.

So there were 3749 eligible patients taking warfarin. Their average age was 75. Forty-three percent of patients were female, and 91% self-identified as white.

The patients’ median time from their first warfarin prescription to baseline was 3.9 years (range, 1.5-7.5 years). Thirty-seven percent of patients were also taking aspirin, and 5% were taking clopidogrel.

Results

INR stability was defined as 80% or more INRs in the therapeutic range (2.0-3.0).

Twenty-six percent of the patients met this definition during the first 6 months, and 34% of these patients maintained stable INRs over the subsequent year.

Ten percent of all patients had 100% of their INR values in the therapeutic range during the first 6 months. Of these patients, 37% met the definition of stability over the subsequent year.

Of the patients who had 80% or more of their INR values in the therapeutic range at baseline, 36% had 1 or more well-out-of-range INRs in the following year.

Of the patients with 100% of their baseline INR values in the therapeutic range, 33% had 1 or more well-out-of-range INRs in the subsequent year.

The researchers said these results suggest warfarin stability is difficult to predict, and this study challenges the notion that patients who have done well taking warfarin should continue taking warfarin.

A novel microfluidic device can be used to monitor thrombus formation and platelet function in patients receiving antiplatelet therapy, according to research published in Biomedical Microdevices.

The device is designed to mimic cellular and vascular flow conditions inside the human body.

Investigators say it demonstrates how endothelial cells contribute to hemostasis, even though it does not contain living endothelial cells.

The device contains microfluidic channels lined with chemically fixed human endothelial cells.

“It’s a bioinspired device that contains the endothelial function of a diseased patient without having actual living cells, and this greatly increases the robustness of the device,” explained study author Abhishek Jain, PhD, of Texas A&M University in College Station, Texas.

D Jain and his colleagues said their device retains the ability to modulate hemostasis under continuous flow in vitro, even after a few days of storage.

And the team successfully used the device to measure thrombus formation and platelet function in small amounts of whole blood from patients receiving antiplatelet therapy.

“Abnormal blood coagulation and platelet activation are major medical problems, and the ways we study them now are overly simplified,” said study author Donald Ingber, MD, PhD, of the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston, Massachusetts.

“Clinicians currently do not have tools to monitor hemostasis that take into account physiologically important interactions between endothelial cells and flowing blood.”

In a previous study, Dr Ingber and his colleagues showed that recreating the physicality and blood flow of vasculature within microfluidic channels allowed them to predict precise times that blood might clot, with potential applications in real-time monitoring of patients receiving anticoagulants.

The group’s new device adds another layer of complexity by embedding the functionality of the vascular endothelium within a tool that might be manufactured, stored, and shipped for clinical use.

“This is one of the first examples of how a microfluidic cell culture system could have added value in clinical diagnostics,” said study author Andries van der Meer, PhD, of University of Twente in Enschede, Netherlands.

“Using chemically fixed tissue that is no longer alive offers a clear, low-risk path toward further testing and product development.”

A novel microfluidic device can be used to monitor thrombus formation and platelet function in patients receiving antiplatelet therapy, according to research published in Biomedical Microdevices.

The device is designed to mimic cellular and vascular flow conditions inside the human body.

Investigators say it demonstrates how endothelial cells contribute to hemostasis, even though it does not contain living endothelial cells.

The device contains microfluidic channels lined with chemically fixed human endothelial cells.

“It’s a bioinspired device that contains the endothelial function of a diseased patient without having actual living cells, and this greatly increases the robustness of the device,” explained study author Abhishek Jain, PhD, of Texas A&M University in College Station, Texas.

D Jain and his colleagues said their device retains the ability to modulate hemostasis under continuous flow in vitro, even after a few days of storage.

And the team successfully used the device to measure thrombus formation and platelet function in small amounts of whole blood from patients receiving antiplatelet therapy.

“Abnormal blood coagulation and platelet activation are major medical problems, and the ways we study them now are overly simplified,” said study author Donald Ingber, MD, PhD, of the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston, Massachusetts.

“Clinicians currently do not have tools to monitor hemostasis that take into account physiologically important interactions between endothelial cells and flowing blood.”

In a previous study, Dr Ingber and his colleagues showed that recreating the physicality and blood flow of vasculature within microfluidic channels allowed them to predict precise times that blood might clot, with potential applications in real-time monitoring of patients receiving anticoagulants.

The group’s new device adds another layer of complexity by embedding the functionality of the vascular endothelium within a tool that might be manufactured, stored, and shipped for clinical use.

“This is one of the first examples of how a microfluidic cell culture system could have added value in clinical diagnostics,” said study author Andries van der Meer, PhD, of University of Twente in Enschede, Netherlands.

“Using chemically fixed tissue that is no longer alive offers a clear, low-risk path toward further testing and product development.”

A novel microfluidic device can be used to monitor thrombus formation and platelet function in patients receiving antiplatelet therapy, according to research published in Biomedical Microdevices.

The device is designed to mimic cellular and vascular flow conditions inside the human body.

Investigators say it demonstrates how endothelial cells contribute to hemostasis, even though it does not contain living endothelial cells.

The device contains microfluidic channels lined with chemically fixed human endothelial cells.

“It’s a bioinspired device that contains the endothelial function of a diseased patient without having actual living cells, and this greatly increases the robustness of the device,” explained study author Abhishek Jain, PhD, of Texas A&M University in College Station, Texas.

D Jain and his colleagues said their device retains the ability to modulate hemostasis under continuous flow in vitro, even after a few days of storage.

And the team successfully used the device to measure thrombus formation and platelet function in small amounts of whole blood from patients receiving antiplatelet therapy.

“Abnormal blood coagulation and platelet activation are major medical problems, and the ways we study them now are overly simplified,” said study author Donald Ingber, MD, PhD, of the Wyss Institute for Biologically Inspired Engineering at Harvard University in Boston, Massachusetts.

“Clinicians currently do not have tools to monitor hemostasis that take into account physiologically important interactions between endothelial cells and flowing blood.”

In a previous study, Dr Ingber and his colleagues showed that recreating the physicality and blood flow of vasculature within microfluidic channels allowed them to predict precise times that blood might clot, with potential applications in real-time monitoring of patients receiving anticoagulants.

The group’s new device adds another layer of complexity by embedding the functionality of the vascular endothelium within a tool that might be manufactured, stored, and shipped for clinical use.

“This is one of the first examples of how a microfluidic cell culture system could have added value in clinical diagnostics,” said study author Andries van der Meer, PhD, of University of Twente in Enschede, Netherlands.

“Using chemically fixed tissue that is no longer alive offers a clear, low-risk path toward further testing and product development.”

Solar-powered mosquito traps incorporating human odor can reduce the incidence of malaria, according to research published in The Lancet.

Researchers introduced these traps to homes on the Kenyan island of Rusinga.

The population of malaria-carrying mosquitoes declined by 42% in homes that had the traps.

And the prevalence of malaria was 30% lower among people living in houses with a trap than among those in houses without a trap.

“The objective of the trial on Rusinga Island in Lake Victoria was to investigate whether malaria mosquitoes can be captured and destroyed using traps with a lure so that the risk of new malaria infections is minimized,” explained study author Willem Takken, PhD, of Wageningen University and Research Centre in Wageningen, Netherlands.

The trial enrolled 34,041 participants. Each individual was assigned to a cluster, which consisted of 50 or 51 geographically contiguous households. There were 81 clusters in all.

The researchers installed their solar-powered, odor-baited mosquito trapping systems (SMoTS) in the various households, cluster by cluster, until all of the clusters had the traps.

During the roll-out period—between June 3, 2013, and May 16, 2015—SMoTS were installed in 4358 households.

The density of Anopheles mosquitoes was lower in the clusters with SMoTS than those without. The adjusted estimated effectiveness of the traps was 42.2%.

The densities of Anopheles funestus and Anopheles gambiae mosquitoes were lower in clusters with SMoTS than those without. The adjusted estimated effectiveness was 69.2% (P=0.005) and 10.8% (P=0.6), respectively.

The prevalence of malaria was 29.8% lower in clusters with SMoTS than those without (P<0.0001).

About 24% of people in clusters with SMoTS were positive for Plasmodium parasites (23.7%, 1552/6550), compared to about 35% of people in clusters without SMoTS (34.5%, 2002/5795).

“Ultimately, we want to eradicate malaria completely, in an environmentally friendly and sustainable manner,” Dr Takken said.

“As we use a natural lure—namely, human odor—in our approach, there is no negative impact on the environment, and it is very improbable that the mosquitoes will become ‘resistant’ to being captured. After all, the mosquitoes need their attraction to the lure in order to be able to survive.”

Dr Takken and his colleagues believe their SMoTS may also be able to combat dengue fever and the Zika virus. Aedes aegypti is a vector for these viruses, and this mosquito is attracted to the same humanized scent that attracts malaria-carrying mosquitoes.

Solar-powered mosquito traps incorporating human odor can reduce the incidence of malaria, according to research published in The Lancet.

Researchers introduced these traps to homes on the Kenyan island of Rusinga.

The population of malaria-carrying mosquitoes declined by 42% in homes that had the traps.

And the prevalence of malaria was 30% lower among people living in houses with a trap than among those in houses without a trap.

“The objective of the trial on Rusinga Island in Lake Victoria was to investigate whether malaria mosquitoes can be captured and destroyed using traps with a lure so that the risk of new malaria infections is minimized,” explained study author Willem Takken, PhD, of Wageningen University and Research Centre in Wageningen, Netherlands.

The trial enrolled 34,041 participants. Each individual was assigned to a cluster, which consisted of 50 or 51 geographically contiguous households. There were 81 clusters in all.

The researchers installed their solar-powered, odor-baited mosquito trapping systems (SMoTS) in the various households, cluster by cluster, until all of the clusters had the traps.

During the roll-out period—between June 3, 2013, and May 16, 2015—SMoTS were installed in 4358 households.

The density of Anopheles mosquitoes was lower in the clusters with SMoTS than those without. The adjusted estimated effectiveness of the traps was 42.2%.

The densities of Anopheles funestus and Anopheles gambiae mosquitoes were lower in clusters with SMoTS than those without. The adjusted estimated effectiveness was 69.2% (P=0.005) and 10.8% (P=0.6), respectively.

The prevalence of malaria was 29.8% lower in clusters with SMoTS than those without (P<0.0001).

About 24% of people in clusters with SMoTS were positive for Plasmodium parasites (23.7%, 1552/6550), compared to about 35% of people in clusters without SMoTS (34.5%, 2002/5795).

“Ultimately, we want to eradicate malaria completely, in an environmentally friendly and sustainable manner,” Dr Takken said.

“As we use a natural lure—namely, human odor—in our approach, there is no negative impact on the environment, and it is very improbable that the mosquitoes will become ‘resistant’ to being captured. After all, the mosquitoes need their attraction to the lure in order to be able to survive.”

Dr Takken and his colleagues believe their SMoTS may also be able to combat dengue fever and the Zika virus. Aedes aegypti is a vector for these viruses, and this mosquito is attracted to the same humanized scent that attracts malaria-carrying mosquitoes.

Solar-powered mosquito traps incorporating human odor can reduce the incidence of malaria, according to research published in The Lancet.

Researchers introduced these traps to homes on the Kenyan island of Rusinga.

The population of malaria-carrying mosquitoes declined by 42% in homes that had the traps.

And the prevalence of malaria was 30% lower among people living in houses with a trap than among those in houses without a trap.

“The objective of the trial on Rusinga Island in Lake Victoria was to investigate whether malaria mosquitoes can be captured and destroyed using traps with a lure so that the risk of new malaria infections is minimized,” explained study author Willem Takken, PhD, of Wageningen University and Research Centre in Wageningen, Netherlands.

The trial enrolled 34,041 participants. Each individual was assigned to a cluster, which consisted of 50 or 51 geographically contiguous households. There were 81 clusters in all.

The researchers installed their solar-powered, odor-baited mosquito trapping systems (SMoTS) in the various households, cluster by cluster, until all of the clusters had the traps.

During the roll-out period—between June 3, 2013, and May 16, 2015—SMoTS were installed in 4358 households.

The density of Anopheles mosquitoes was lower in the clusters with SMoTS than those without. The adjusted estimated effectiveness of the traps was 42.2%.

The densities of Anopheles funestus and Anopheles gambiae mosquitoes were lower in clusters with SMoTS than those without. The adjusted estimated effectiveness was 69.2% (P=0.005) and 10.8% (P=0.6), respectively.

The prevalence of malaria was 29.8% lower in clusters with SMoTS than those without (P<0.0001).

About 24% of people in clusters with SMoTS were positive for Plasmodium parasites (23.7%, 1552/6550), compared to about 35% of people in clusters without SMoTS (34.5%, 2002/5795).

“Ultimately, we want to eradicate malaria completely, in an environmentally friendly and sustainable manner,” Dr Takken said.

“As we use a natural lure—namely, human odor—in our approach, there is no negative impact on the environment, and it is very improbable that the mosquitoes will become ‘resistant’ to being captured. After all, the mosquitoes need their attraction to the lure in order to be able to survive.”

Dr Takken and his colleagues believe their SMoTS may also be able to combat dengue fever and the Zika virus. Aedes aegypti is a vector for these viruses, and this mosquito is attracted to the same humanized scent that attracts malaria-carrying mosquitoes.

Preclinical research has revealed malfunctioning molecular pathways associated with cardiac anomalies in sickle cell anemia (SCA) that lead to sudden death.

Researchers used a mouse model of SCA and identified a unique “restrictive cardiomyopathy” that is superimposed on the anemia-associated heart enlargement.

They also found upregulated gene expression that fuels myocardial fibrosis and electrophysiological changes.

The researchers believe these findings, published in PNAS, will aid the development of new targeted therapies to treat cardiac dysfunction in patients with SCA.

“Sickle cell anemia is associated with significant morbidity and mortality, including a high incidence of unexplained, sudden death in young adults,” said study author Punam Malik, MD, of Cincinnati Children’s Hospital Medical Center in Ohio.

“Our findings may provide a unifying cardiac pathophysiology that explains reported cardiac abnormalities and sudden death seen in humans with SCA.”

To find pathologies specific to SCA, Dr Malik and his colleagues compared mice bred to have SCA and wild-type mice with experimentally induced chronic anemia.

The mice underwent serial comprehensive cardiac analysis, including detailed cardiac imaging (MRI), electrocardiography, and microscopic cross-section analysis of heart tissues (histopathology and electron microscopy).

The researchers said that, in the SCA mice, they observed a distinctive sickle cardiomyopathy in which restrictive physiology was superimposed on chronic anemia and predisposed the mice to sudden death.

The SCA mice had progressive left atrial enlargement and diastolic dysfunction but preserved systolic function. This restrictive physiology appeared to be caused by ischemic-scattered cardiomyocyte loss, myocardial fibrosis, and cardiac remodeling.

The researchers also conducted transcriptome analysis. This revealed that SCA mice had upregulation of genes that cause increased oxidation, hypoxia, and fibrosis in heart tissues. It also showed a downregulation of genes associated with electrophysiological function.

Finally, the team observed progressive corrected QT prolongation, arrhythmias, and ischemic changes in the SCA mice shortly before a significant number of the animals experienced sudden death.

The researchers are continuing to study the molecular mechanisms and pathways that trigger myocardial fibrosis in SCA, using a variety of knockout mice.

In addition, the successful use of noninvasive cardiac imaging techniques in this study inspired the researchers to launch a clinical trial to test these early diagnostic techniques on people with SCA. Enrollment in that study is now complete.

“It is incredibly exciting to see that this work has inspired clinical trials and other research studies,” said study author Nihal Bakeer, MD, of the Indiana Hemophilia and Thrombosis Center in Indianapolis.

“Our goal has always been [to] find the underling pathobiology of cardiac complications in sickle cell anemia and help find new diagnostics and therapeutics to decrease the morbidity and rate of sudden cardiac death in young adults with SCA.”

Preclinical research has revealed malfunctioning molecular pathways associated with cardiac anomalies in sickle cell anemia (SCA) that lead to sudden death.

Researchers used a mouse model of SCA and identified a unique “restrictive cardiomyopathy” that is superimposed on the anemia-associated heart enlargement.

They also found upregulated gene expression that fuels myocardial fibrosis and electrophysiological changes.

The researchers believe these findings, published in PNAS, will aid the development of new targeted therapies to treat cardiac dysfunction in patients with SCA.

“Sickle cell anemia is associated with significant morbidity and mortality, including a high incidence of unexplained, sudden death in young adults,” said study author Punam Malik, MD, of Cincinnati Children’s Hospital Medical Center in Ohio.

“Our findings may provide a unifying cardiac pathophysiology that explains reported cardiac abnormalities and sudden death seen in humans with SCA.”

To find pathologies specific to SCA, Dr Malik and his colleagues compared mice bred to have SCA and wild-type mice with experimentally induced chronic anemia.

The mice underwent serial comprehensive cardiac analysis, including detailed cardiac imaging (MRI), electrocardiography, and microscopic cross-section analysis of heart tissues (histopathology and electron microscopy).

The researchers said that, in the SCA mice, they observed a distinctive sickle cardiomyopathy in which restrictive physiology was superimposed on chronic anemia and predisposed the mice to sudden death.

The SCA mice had progressive left atrial enlargement and diastolic dysfunction but preserved systolic function. This restrictive physiology appeared to be caused by ischemic-scattered cardiomyocyte loss, myocardial fibrosis, and cardiac remodeling.

The researchers also conducted transcriptome analysis. This revealed that SCA mice had upregulation of genes that cause increased oxidation, hypoxia, and fibrosis in heart tissues. It also showed a downregulation of genes associated with electrophysiological function.

Finally, the team observed progressive corrected QT prolongation, arrhythmias, and ischemic changes in the SCA mice shortly before a significant number of the animals experienced sudden death.

The researchers are continuing to study the molecular mechanisms and pathways that trigger myocardial fibrosis in SCA, using a variety of knockout mice.

In addition, the successful use of noninvasive cardiac imaging techniques in this study inspired the researchers to launch a clinical trial to test these early diagnostic techniques on people with SCA. Enrollment in that study is now complete.

“It is incredibly exciting to see that this work has inspired clinical trials and other research studies,” said study author Nihal Bakeer, MD, of the Indiana Hemophilia and Thrombosis Center in Indianapolis.

“Our goal has always been [to] find the underling pathobiology of cardiac complications in sickle cell anemia and help find new diagnostics and therapeutics to decrease the morbidity and rate of sudden cardiac death in young adults with SCA.”

Preclinical research has revealed malfunctioning molecular pathways associated with cardiac anomalies in sickle cell anemia (SCA) that lead to sudden death.

Researchers used a mouse model of SCA and identified a unique “restrictive cardiomyopathy” that is superimposed on the anemia-associated heart enlargement.

They also found upregulated gene expression that fuels myocardial fibrosis and electrophysiological changes.

The researchers believe these findings, published in PNAS, will aid the development of new targeted therapies to treat cardiac dysfunction in patients with SCA.

“Sickle cell anemia is associated with significant morbidity and mortality, including a high incidence of unexplained, sudden death in young adults,” said study author Punam Malik, MD, of Cincinnati Children’s Hospital Medical Center in Ohio.

“Our findings may provide a unifying cardiac pathophysiology that explains reported cardiac abnormalities and sudden death seen in humans with SCA.”

To find pathologies specific to SCA, Dr Malik and his colleagues compared mice bred to have SCA and wild-type mice with experimentally induced chronic anemia.

The mice underwent serial comprehensive cardiac analysis, including detailed cardiac imaging (MRI), electrocardiography, and microscopic cross-section analysis of heart tissues (histopathology and electron microscopy).

The researchers said that, in the SCA mice, they observed a distinctive sickle cardiomyopathy in which restrictive physiology was superimposed on chronic anemia and predisposed the mice to sudden death.

The SCA mice had progressive left atrial enlargement and diastolic dysfunction but preserved systolic function. This restrictive physiology appeared to be caused by ischemic-scattered cardiomyocyte loss, myocardial fibrosis, and cardiac remodeling.

The researchers also conducted transcriptome analysis. This revealed that SCA mice had upregulation of genes that cause increased oxidation, hypoxia, and fibrosis in heart tissues. It also showed a downregulation of genes associated with electrophysiological function.

Finally, the team observed progressive corrected QT prolongation, arrhythmias, and ischemic changes in the SCA mice shortly before a significant number of the animals experienced sudden death.

The researchers are continuing to study the molecular mechanisms and pathways that trigger myocardial fibrosis in SCA, using a variety of knockout mice.

In addition, the successful use of noninvasive cardiac imaging techniques in this study inspired the researchers to launch a clinical trial to test these early diagnostic techniques on people with SCA. Enrollment in that study is now complete.

“It is incredibly exciting to see that this work has inspired clinical trials and other research studies,” said study author Nihal Bakeer, MD, of the Indiana Hemophilia and Thrombosis Center in Indianapolis.

“Our goal has always been [to] find the underling pathobiology of cardiac complications in sickle cell anemia and help find new diagnostics and therapeutics to decrease the morbidity and rate of sudden cardiac death in young adults with SCA.”

The psychosocial impact of epilepsy on children and adolescents is profound, ranging from a sense of vulnerability and disempowerment to discrimination, results from a systematic review of medical literature suggest.

“Children and adolescents perceive that epilepsy forces them to relinquish their sense of privacy, bodily control, normality, freedom, and confidence to participate in school and social activities,” researchers led by Lauren Chong wrote in a study published online Aug. 10 in Pediatrics. “They are overwhelmed by the daily uncertainties attributed to the unpredictable timing and potential harm from seizures, side effects of ongoing treatment, and the impermanence of remission.”

©IvelinRadkov/Thinkstock

In an effort to describe the perspectives of children and adolescents with epilepsy, Ms. Chong of the Sydney School of Public Health at the University of Sydney, New South Wales, Australia, and her associates searched Medline and other key databases for qualitative primary studies on children’s experience of epilepsy from inception to August 2015 (Pediatrics. 2016;138[3]:e20160658. doi: 10.1542/peds.2016-0658). They used thematic synthesis to analyze their findings. The final analysis included 43 articles involving 951 children and adolescents aged 3-21 years from 21 different countries. Articles written in a language other than English were excluded.

The researchers identified six themes: loss of bodily control such as a sense of being overtaken and alertness to mortality; loss of privacy such as humiliating involuntary function and unwanted special attention; inescapable inferiority and discrimination such as vulnerability to prejudice and inability to achieve academically; therapeutic burden and futility such as financial burden and insurmountable side effects; navigating health care such as unexpected necessity of transition as well as fragmented and inconsistent care; and recontextualizing to regain normality such as distinguishing disease from identity and gaining perspective and maturity.

The researchers observed some differences in experiences and perspectives based on patient age and disease severity. For example, “feelings of loss and abnormality tended to be expressed more strongly by older adolescent patients,” they wrote. “As young adults, they were aware of the potentially serious ramifications of epilepsy on their future, including their independence, school performance, vocation, and relationships. Teenage patients were more frustrated by social limitations on partying, drinking, and sleepovers that differentiated them from their peers.” Patients with more severe disease, meanwhile, “contended with disempowerment and seemed less able to delineate epilepsy from their identity. They seemed more willing to trial therapies that may work and some, on being told they would not achieve remission, chose to disengage from the health care system, deeming further treatment or follow-up to be futile.”

Suggestions for clinical practice based on the analysis include providing access to support groups of other epilepsy sufferers or other children/adolescents with chronic disease; facilitating liaisons between clinicians, families, and school teachers, and delivering coordinated care with psychologists and psychiatrists to address psychosocial aspects of epilepsy.

“Treatment and management should address the psychosocial needs of patients regarding stigma, present lifestyle limitations, and future concerns,” the researchers wrote. “These suggestions may inform strategies for practice and research that may contribute toward the improved [quality of life], therapeutic satisfaction, and health outcomes of children and adolescents with epilepsy.”

Ms. Chong is supported by the University of Sydney Neuroscience Network Research Scholarship. Another coauthor, Allison Tong, PhD, is supported by the National Health and Medical Research Council Fellowship. The researchers reported having no financial disclosures.

[email protected]

The psychosocial impact of epilepsy on children and adolescents is profound, ranging from a sense of vulnerability and disempowerment to discrimination, results from a systematic review of medical literature suggest.

“Children and adolescents perceive that epilepsy forces them to relinquish their sense of privacy, bodily control, normality, freedom, and confidence to participate in school and social activities,” researchers led by Lauren Chong wrote in a study published online Aug. 10 in Pediatrics. “They are overwhelmed by the daily uncertainties attributed to the unpredictable timing and potential harm from seizures, side effects of ongoing treatment, and the impermanence of remission.”

©IvelinRadkov/Thinkstock

In an effort to describe the perspectives of children and adolescents with epilepsy, Ms. Chong of the Sydney School of Public Health at the University of Sydney, New South Wales, Australia, and her associates searched Medline and other key databases for qualitative primary studies on children’s experience of epilepsy from inception to August 2015 (Pediatrics. 2016;138[3]:e20160658. doi: 10.1542/peds.2016-0658). They used thematic synthesis to analyze their findings. The final analysis included 43 articles involving 951 children and adolescents aged 3-21 years from 21 different countries. Articles written in a language other than English were excluded.

The researchers identified six themes: loss of bodily control such as a sense of being overtaken and alertness to mortality; loss of privacy such as humiliating involuntary function and unwanted special attention; inescapable inferiority and discrimination such as vulnerability to prejudice and inability to achieve academically; therapeutic burden and futility such as financial burden and insurmountable side effects; navigating health care such as unexpected necessity of transition as well as fragmented and inconsistent care; and recontextualizing to regain normality such as distinguishing disease from identity and gaining perspective and maturity.

The researchers observed some differences in experiences and perspectives based on patient age and disease severity. For example, “feelings of loss and abnormality tended to be expressed more strongly by older adolescent patients,” they wrote. “As young adults, they were aware of the potentially serious ramifications of epilepsy on their future, including their independence, school performance, vocation, and relationships. Teenage patients were more frustrated by social limitations on partying, drinking, and sleepovers that differentiated them from their peers.” Patients with more severe disease, meanwhile, “contended with disempowerment and seemed less able to delineate epilepsy from their identity. They seemed more willing to trial therapies that may work and some, on being told they would not achieve remission, chose to disengage from the health care system, deeming further treatment or follow-up to be futile.”

Suggestions for clinical practice based on the analysis include providing access to support groups of other epilepsy sufferers or other children/adolescents with chronic disease; facilitating liaisons between clinicians, families, and school teachers, and delivering coordinated care with psychologists and psychiatrists to address psychosocial aspects of epilepsy.

“Treatment and management should address the psychosocial needs of patients regarding stigma, present lifestyle limitations, and future concerns,” the researchers wrote. “These suggestions may inform strategies for practice and research that may contribute toward the improved [quality of life], therapeutic satisfaction, and health outcomes of children and adolescents with epilepsy.”

Ms. Chong is supported by the University of Sydney Neuroscience Network Research Scholarship. Another coauthor, Allison Tong, PhD, is supported by the National Health and Medical Research Council Fellowship. The researchers reported having no financial disclosures.

[email protected]

The psychosocial impact of epilepsy on children and adolescents is profound, ranging from a sense of vulnerability and disempowerment to discrimination, results from a systematic review of medical literature suggest.

“Children and adolescents perceive that epilepsy forces them to relinquish their sense of privacy, bodily control, normality, freedom, and confidence to participate in school and social activities,” researchers led by Lauren Chong wrote in a study published online Aug. 10 in Pediatrics. “They are overwhelmed by the daily uncertainties attributed to the unpredictable timing and potential harm from seizures, side effects of ongoing treatment, and the impermanence of remission.”

©IvelinRadkov/Thinkstock

In an effort to describe the perspectives of children and adolescents with epilepsy, Ms. Chong of the Sydney School of Public Health at the University of Sydney, New South Wales, Australia, and her associates searched Medline and other key databases for qualitative primary studies on children’s experience of epilepsy from inception to August 2015 (Pediatrics. 2016;138[3]:e20160658. doi: 10.1542/peds.2016-0658). They used thematic synthesis to analyze their findings. The final analysis included 43 articles involving 951 children and adolescents aged 3-21 years from 21 different countries. Articles written in a language other than English were excluded.

The researchers identified six themes: loss of bodily control such as a sense of being overtaken and alertness to mortality; loss of privacy such as humiliating involuntary function and unwanted special attention; inescapable inferiority and discrimination such as vulnerability to prejudice and inability to achieve academically; therapeutic burden and futility such as financial burden and insurmountable side effects; navigating health care such as unexpected necessity of transition as well as fragmented and inconsistent care; and recontextualizing to regain normality such as distinguishing disease from identity and gaining perspective and maturity.

The researchers observed some differences in experiences and perspectives based on patient age and disease severity. For example, “feelings of loss and abnormality tended to be expressed more strongly by older adolescent patients,” they wrote. “As young adults, they were aware of the potentially serious ramifications of epilepsy on their future, including their independence, school performance, vocation, and relationships. Teenage patients were more frustrated by social limitations on partying, drinking, and sleepovers that differentiated them from their peers.” Patients with more severe disease, meanwhile, “contended with disempowerment and seemed less able to delineate epilepsy from their identity. They seemed more willing to trial therapies that may work and some, on being told they would not achieve remission, chose to disengage from the health care system, deeming further treatment or follow-up to be futile.”

Suggestions for clinical practice based on the analysis include providing access to support groups of other epilepsy sufferers or other children/adolescents with chronic disease; facilitating liaisons between clinicians, families, and school teachers, and delivering coordinated care with psychologists and psychiatrists to address psychosocial aspects of epilepsy.

“Treatment and management should address the psychosocial needs of patients regarding stigma, present lifestyle limitations, and future concerns,” the researchers wrote. “These suggestions may inform strategies for practice and research that may contribute toward the improved [quality of life], therapeutic satisfaction, and health outcomes of children and adolescents with epilepsy.”

Ms. Chong is supported by the University of Sydney Neuroscience Network Research Scholarship. Another coauthor, Allison Tong, PhD, is supported by the National Health and Medical Research Council Fellowship. The researchers reported having no financial disclosures.

[email protected]

Congenital Zika syndrome should be added to the differential diagnosis of congenital infections and arthrogryposis (joint contractures), results from a case series study in Brazil suggest.

“Brain impairment in the presence of microcephaly is the main characteristic of a congenital Zika virus syndrome,” researchers led by Vanessa van der Linden, MD, wrote in a study published online Aug. 9 in the BMJ. “However, little is still known about this condition and its clinical spectrum, which also concerns newborns with a normal head circumference. Two studies have described the association between arthrogryposis and microcephaly in newborns presumed to have congenital Zika virus infection [See Morb Mortal Wkly. Rep. 2016;65:59-62 and Ultrasound Obstet Gynecol. 2016;47:6-7].” The authors went on to note that while arthrogryposis might be considered more of a sign than a specific disease, “it might be associated with several disorders. However, there are no reports in the literature about other congenital infections in humans associated with arthrogryposis.”

©Devonyu/Thinkstock

Dr. van der Linden, a pediatric neurologist with the Association for Assistance of Disabled Children, Recife, Brazil, and her associates retrospectively evaluated the medical records of seven patients with arthrogryposis associated with congenital infection believed to be caused by Zika virus, during the Brazilian microcephaly epidemic (BMJ. 2016;354:i3899). The main outcomes of interest were clinical, radiologic, and electromyographic findings, and likely collaboration between clinical and primary neurological abnormalities.

The researchers reported that brain images of all seven children revealed characteristics of congenital infection and arthrogryposis. Two children (29%) tested positive for IgM antibody for Zika virus in the cerebrospinal fluid, while arthrogryposis was present in the arms and legs of six children (86%) and in the legs of one child (14%). In addition, hip x-rays showed bilateral dislocation in all seven children and subluxation of the knee associated with genu valgus in three (43%). No evidence of abnormalities was seen on high-definition ultrasonography of the joints, but moderate signs of remodeling of the motor units and a reduced recruitment pattern were found on needle electromyography. Results from brain computed tomography conducted in all seven patients and magnetic resonance imaging conducted in five revealed malformations of cortical development, calcifications predominantly in the cortex and subcortical white matter, reduction in brain volume, ventriculomegaly, and hypoplasia of the brainstem and cerebellum. Spinal MRI conducted in four children showed apparent thinning of the cord and reduced ventral roots.

“Further research is needed with a larger number of cases to study the neurological abnormalities behind arthrogryposis, including histopathology of autopsy samples or tissues from stillborn babies,” the researchers concluded. “As we do not know the potential implications of congenital Zika virus infection as it evolves, children must receive orthopedic follow-up, even those with a standard first orthopedic evaluation, because they could develop musculoskeletal deformities secondary to neurological impairment, central or peripheral, or both, as these occur in patients with cerebral palsy and other chronic encephalopathies.”

The researchers reported having no financial disclosures.

[email protected]

Congenital Zika syndrome should be added to the differential diagnosis of congenital infections and arthrogryposis (joint contractures), results from a case series study in Brazil suggest.

“Brain impairment in the presence of microcephaly is the main characteristic of a congenital Zika virus syndrome,” researchers led by Vanessa van der Linden, MD, wrote in a study published online Aug. 9 in the BMJ. “However, little is still known about this condition and its clinical spectrum, which also concerns newborns with a normal head circumference. Two studies have described the association between arthrogryposis and microcephaly in newborns presumed to have congenital Zika virus infection [See Morb Mortal Wkly. Rep. 2016;65:59-62 and Ultrasound Obstet Gynecol. 2016;47:6-7].” The authors went on to note that while arthrogryposis might be considered more of a sign than a specific disease, “it might be associated with several disorders. However, there are no reports in the literature about other congenital infections in humans associated with arthrogryposis.”

©Devonyu/Thinkstock

Dr. van der Linden, a pediatric neurologist with the Association for Assistance of Disabled Children, Recife, Brazil, and her associates retrospectively evaluated the medical records of seven patients with arthrogryposis associated with congenital infection believed to be caused by Zika virus, during the Brazilian microcephaly epidemic (BMJ. 2016;354:i3899). The main outcomes of interest were clinical, radiologic, and electromyographic findings, and likely collaboration between clinical and primary neurological abnormalities.

The researchers reported that brain images of all seven children revealed characteristics of congenital infection and arthrogryposis. Two children (29%) tested positive for IgM antibody for Zika virus in the cerebrospinal fluid, while arthrogryposis was present in the arms and legs of six children (86%) and in the legs of one child (14%). In addition, hip x-rays showed bilateral dislocation in all seven children and subluxation of the knee associated with genu valgus in three (43%). No evidence of abnormalities was seen on high-definition ultrasonography of the joints, but moderate signs of remodeling of the motor units and a reduced recruitment pattern were found on needle electromyography. Results from brain computed tomography conducted in all seven patients and magnetic resonance imaging conducted in five revealed malformations of cortical development, calcifications predominantly in the cortex and subcortical white matter, reduction in brain volume, ventriculomegaly, and hypoplasia of the brainstem and cerebellum. Spinal MRI conducted in four children showed apparent thinning of the cord and reduced ventral roots.

“Further research is needed with a larger number of cases to study the neurological abnormalities behind arthrogryposis, including histopathology of autopsy samples or tissues from stillborn babies,” the researchers concluded. “As we do not know the potential implications of congenital Zika virus infection as it evolves, children must receive orthopedic follow-up, even those with a standard first orthopedic evaluation, because they could develop musculoskeletal deformities secondary to neurological impairment, central or peripheral, or both, as these occur in patients with cerebral palsy and other chronic encephalopathies.”

The researchers reported having no financial disclosures.

[email protected]

Congenital Zika syndrome should be added to the differential diagnosis of congenital infections and arthrogryposis (joint contractures), results from a case series study in Brazil suggest.

“Brain impairment in the presence of microcephaly is the main characteristic of a congenital Zika virus syndrome,” researchers led by Vanessa van der Linden, MD, wrote in a study published online Aug. 9 in the BMJ. “However, little is still known about this condition and its clinical spectrum, which also concerns newborns with a normal head circumference. Two studies have described the association between arthrogryposis and microcephaly in newborns presumed to have congenital Zika virus infection [See Morb Mortal Wkly. Rep. 2016;65:59-62 and Ultrasound Obstet Gynecol. 2016;47:6-7].” The authors went on to note that while arthrogryposis might be considered more of a sign than a specific disease, “it might be associated with several disorders. However, there are no reports in the literature about other congenital infections in humans associated with arthrogryposis.”

©Devonyu/Thinkstock

Dr. van der Linden, a pediatric neurologist with the Association for Assistance of Disabled Children, Recife, Brazil, and her associates retrospectively evaluated the medical records of seven patients with arthrogryposis associated with congenital infection believed to be caused by Zika virus, during the Brazilian microcephaly epidemic (BMJ. 2016;354:i3899). The main outcomes of interest were clinical, radiologic, and electromyographic findings, and likely collaboration between clinical and primary neurological abnormalities.

The researchers reported that brain images of all seven children revealed characteristics of congenital infection and arthrogryposis. Two children (29%) tested positive for IgM antibody for Zika virus in the cerebrospinal fluid, while arthrogryposis was present in the arms and legs of six children (86%) and in the legs of one child (14%). In addition, hip x-rays showed bilateral dislocation in all seven children and subluxation of the knee associated with genu valgus in three (43%). No evidence of abnormalities was seen on high-definition ultrasonography of the joints, but moderate signs of remodeling of the motor units and a reduced recruitment pattern were found on needle electromyography. Results from brain computed tomography conducted in all seven patients and magnetic resonance imaging conducted in five revealed malformations of cortical development, calcifications predominantly in the cortex and subcortical white matter, reduction in brain volume, ventriculomegaly, and hypoplasia of the brainstem and cerebellum. Spinal MRI conducted in four children showed apparent thinning of the cord and reduced ventral roots.

“Further research is needed with a larger number of cases to study the neurological abnormalities behind arthrogryposis, including histopathology of autopsy samples or tissues from stillborn babies,” the researchers concluded. “As we do not know the potential implications of congenital Zika virus infection as it evolves, children must receive orthopedic follow-up, even those with a standard first orthopedic evaluation, because they could develop musculoskeletal deformities secondary to neurological impairment, central or peripheral, or both, as these occur in patients with cerebral palsy and other chronic encephalopathies.”

The researchers reported having no financial disclosures.

[email protected]

Case Report

A 41-year-old man with no dermatologic history presented for a skin examination. During a full-body skin examination, a lesion was identified on the right third toe that was partially visible underneath the nail plate. The patient stated that the lesion had been present for many years and did not appear to be growing but did cause occasional pain. On examination a 1-cm verrucous, hyperkeratotic, tan papule was noted at the distal end of the nail bed causing partial onycholysis (Figure 1). It was not tender to palpation.

A shave biopsy was obtained of the visible portion of the lesion, which revealed hyperkeratosis, acanthosis, and a population of dermal spindle cells in a myxoid stroma that could not be definitively identified. Special stains were nondiagnostic. The patient was referred to dermatologic surgery for rebiopsy of the lesion after removal of the nail plate. Mature bone was seen embedded in the dermis (Figure 2), and a diagnosis of subungual exostosis was made. Radiography of the digit confirmed a bony excrescence from the tuft of the toe, and the patient was referred to orthopedic surgery for definitive excision. There was no evidence of recurrence at 1-year follow-up.

Comment

Subungual exostosis is an uncommon benign bone tumor located beneath or adjacent to the nail bed on the dorsal aspect of the distal phalanx.¹ Although it can occur on any digit, 70% to 80% of cases have arisen on the distal phalanx of the hallux.² Both sexes are equally susceptible. The majority of lesions occur during the second or third decades of life and usually are asymptomatic unless there is trauma or infection. Growth of the lesion over time can cause lifting or deformity of the nail plate and can cause slight discomfort while walking if located on the great toe.³ Common differential diagnoses include osteochondroma, wart, fibroma, paronychia, myositis ossificans, and pyogenic granuloma.^3,4 Diagnosis can be confirmed with radiography, which should be performed prior to any biopsy or invasive procedure. In our patient, initial radiography could have obviated the need for 2 biopsies prior to definitive excision. Histopathologic evaluation typically reveals mature trabecular bone (Figure 2) surrounded by a fibrocartilage cap.

Subungual exostosis begins as an area of proliferating fibrous tissue with cartilaginous metaplasia located beneath or adjacent to the nail bed on the dorsal aspect of the distal phalanx.¹ This cartilage undergoes enchondral ossification and is converted to trabecular bone. As the lesion grows and matures, the cartilaginous cap blends imperceptibly with the nail bed and comes into continuity with the underlying distal phalanx.^1,3 This process continues until the lesion fuses completely with the distal phalanx.¹ Although the cause of subungual exostosis has not been clearly established, chronic irritation, trauma, and chronic infections are considered causative factors of fibrocartilaginous metaplasia.⁴

 

The most commonly accepted treatment of subungual exostosis is a localized excision. Partial or total removal of the nail has traditionally be advocated to ensure complete excision of the exostosis, a nail-sparing technique that has been shown to enhance cosmetic results.³ Incomplete excision and incomplete maturation of the lesion have been reported to be responsible for almost 50% of recurrences.³ This high recurrence rate is due to difficulty in ensuring a total excision because the gradual merging of the fibrocartilage cap with the overlying nail bed makes it impossible to develop a cleavage plane⁵; as a result, it has been suggested that excision should only be attempted after maturation of the tumor so the cleavage plane can fully develop. Other studies claim that delaying treatment can result in elevation and deformity of the nail, pain, and secondary periungual infection.³

Conclusion

Subungual exostosis is a benign bony tumor of the distal phalanx that can cause pain and onycholysis. Radiography of the affected digit is a noninvasive way to confirm the diagnosis and should be part of the initial workup of any suspicious subungual tumor. Once identified, complete removal of the exostosis by excision has been shown to be an effective treatment with few complications.

Case Report

A 41-year-old man with no dermatologic history presented for a skin examination. During a full-body skin examination, a lesion was identified on the right third toe that was partially visible underneath the nail plate. The patient stated that the lesion had been present for many years and did not appear to be growing but did cause occasional pain. On examination a 1-cm verrucous, hyperkeratotic, tan papule was noted at the distal end of the nail bed causing partial onycholysis (Figure 1). It was not tender to palpation.

A shave biopsy was obtained of the visible portion of the lesion, which revealed hyperkeratosis, acanthosis, and a population of dermal spindle cells in a myxoid stroma that could not be definitively identified. Special stains were nondiagnostic. The patient was referred to dermatologic surgery for rebiopsy of the lesion after removal of the nail plate. Mature bone was seen embedded in the dermis (Figure 2), and a diagnosis of subungual exostosis was made. Radiography of the digit confirmed a bony excrescence from the tuft of the toe, and the patient was referred to orthopedic surgery for definitive excision. There was no evidence of recurrence at 1-year follow-up.

Comment

Subungual exostosis is an uncommon benign bone tumor located beneath or adjacent to the nail bed on the dorsal aspect of the distal phalanx.¹ Although it can occur on any digit, 70% to 80% of cases have arisen on the distal phalanx of the hallux.² Both sexes are equally susceptible. The majority of lesions occur during the second or third decades of life and usually are asymptomatic unless there is trauma or infection. Growth of the lesion over time can cause lifting or deformity of the nail plate and can cause slight discomfort while walking if located on the great toe.³ Common differential diagnoses include osteochondroma, wart, fibroma, paronychia, myositis ossificans, and pyogenic granuloma.^3,4 Diagnosis can be confirmed with radiography, which should be performed prior to any biopsy or invasive procedure. In our patient, initial radiography could have obviated the need for 2 biopsies prior to definitive excision. Histopathologic evaluation typically reveals mature trabecular bone (Figure 2) surrounded by a fibrocartilage cap.

Subungual exostosis begins as an area of proliferating fibrous tissue with cartilaginous metaplasia located beneath or adjacent to the nail bed on the dorsal aspect of the distal phalanx.¹ This cartilage undergoes enchondral ossification and is converted to trabecular bone. As the lesion grows and matures, the cartilaginous cap blends imperceptibly with the nail bed and comes into continuity with the underlying distal phalanx.^1,3 This process continues until the lesion fuses completely with the distal phalanx.¹ Although the cause of subungual exostosis has not been clearly established, chronic irritation, trauma, and chronic infections are considered causative factors of fibrocartilaginous metaplasia.⁴

 

The most commonly accepted treatment of subungual exostosis is a localized excision. Partial or total removal of the nail has traditionally be advocated to ensure complete excision of the exostosis, a nail-sparing technique that has been shown to enhance cosmetic results.³ Incomplete excision and incomplete maturation of the lesion have been reported to be responsible for almost 50% of recurrences.³ This high recurrence rate is due to difficulty in ensuring a total excision because the gradual merging of the fibrocartilage cap with the overlying nail bed makes it impossible to develop a cleavage plane⁵; as a result, it has been suggested that excision should only be attempted after maturation of the tumor so the cleavage plane can fully develop. Other studies claim that delaying treatment can result in elevation and deformity of the nail, pain, and secondary periungual infection.³

Conclusion

Subungual exostosis is a benign bony tumor of the distal phalanx that can cause pain and onycholysis. Radiography of the affected digit is a noninvasive way to confirm the diagnosis and should be part of the initial workup of any suspicious subungual tumor. Once identified, complete removal of the exostosis by excision has been shown to be an effective treatment with few complications.

Case Report

A 41-year-old man with no dermatologic history presented for a skin examination. During a full-body skin examination, a lesion was identified on the right third toe that was partially visible underneath the nail plate. The patient stated that the lesion had been present for many years and did not appear to be growing but did cause occasional pain. On examination a 1-cm verrucous, hyperkeratotic, tan papule was noted at the distal end of the nail bed causing partial onycholysis (Figure 1). It was not tender to palpation.

A shave biopsy was obtained of the visible portion of the lesion, which revealed hyperkeratosis, acanthosis, and a population of dermal spindle cells in a myxoid stroma that could not be definitively identified. Special stains were nondiagnostic. The patient was referred to dermatologic surgery for rebiopsy of the lesion after removal of the nail plate. Mature bone was seen embedded in the dermis (Figure 2), and a diagnosis of subungual exostosis was made. Radiography of the digit confirmed a bony excrescence from the tuft of the toe, and the patient was referred to orthopedic surgery for definitive excision. There was no evidence of recurrence at 1-year follow-up.

Comment

Subungual exostosis is an uncommon benign bone tumor located beneath or adjacent to the nail bed on the dorsal aspect of the distal phalanx.¹ Although it can occur on any digit, 70% to 80% of cases have arisen on the distal phalanx of the hallux.² Both sexes are equally susceptible. The majority of lesions occur during the second or third decades of life and usually are asymptomatic unless there is trauma or infection. Growth of the lesion over time can cause lifting or deformity of the nail plate and can cause slight discomfort while walking if located on the great toe.³ Common differential diagnoses include osteochondroma, wart, fibroma, paronychia, myositis ossificans, and pyogenic granuloma.^3,4 Diagnosis can be confirmed with radiography, which should be performed prior to any biopsy or invasive procedure. In our patient, initial radiography could have obviated the need for 2 biopsies prior to definitive excision. Histopathologic evaluation typically reveals mature trabecular bone (Figure 2) surrounded by a fibrocartilage cap.

Subungual exostosis begins as an area of proliferating fibrous tissue with cartilaginous metaplasia located beneath or adjacent to the nail bed on the dorsal aspect of the distal phalanx.¹ This cartilage undergoes enchondral ossification and is converted to trabecular bone. As the lesion grows and matures, the cartilaginous cap blends imperceptibly with the nail bed and comes into continuity with the underlying distal phalanx.^1,3 This process continues until the lesion fuses completely with the distal phalanx.¹ Although the cause of subungual exostosis has not been clearly established, chronic irritation, trauma, and chronic infections are considered causative factors of fibrocartilaginous metaplasia.⁴

 

The most commonly accepted treatment of subungual exostosis is a localized excision. Partial or total removal of the nail has traditionally be advocated to ensure complete excision of the exostosis, a nail-sparing technique that has been shown to enhance cosmetic results.³ Incomplete excision and incomplete maturation of the lesion have been reported to be responsible for almost 50% of recurrences.³ This high recurrence rate is due to difficulty in ensuring a total excision because the gradual merging of the fibrocartilage cap with the overlying nail bed makes it impossible to develop a cleavage plane⁵; as a result, it has been suggested that excision should only be attempted after maturation of the tumor so the cleavage plane can fully develop. Other studies claim that delaying treatment can result in elevation and deformity of the nail, pain, and secondary periungual infection.³

Conclusion

Subungual exostosis is a benign bony tumor of the distal phalanx that can cause pain and onycholysis. Radiography of the affected digit is a noninvasive way to confirm the diagnosis and should be part of the initial workup of any suspicious subungual tumor. Once identified, complete removal of the exostosis by excision has been shown to be an effective treatment with few complications.

“The licensed vaccines HPV-16/18 AS04–adjuvanted (Cervarix; GSK Vaccines) and HPV-6/11/16/18 (Gardasil; Merck) were first approved as regimen including three doses (3D) with administration over a 6-month period,” reported Thanyawee Puthanakit, MD, of Chulalongkorn University in Bangkok, and her associates. “Reduced dose schedules could make vaccination easier to implement and more affordable, creating the potential for higher vaccination coverage and improved cervical cancer protection (J Infect Dis. 2016;214:525-36).”

©jarun011/Thinkstock

The investigators enrolled girls aged 9-25 years starting in June 2011, from 33 clinical sites in Canada, Germany, Italy, Taiwan, and Thailand. The study lasted through January 2013, during which time 1,447 girls were enrolled and 1,428 were randomized into one of three cohorts: one receiving the two-dose, 6-month regimen; one receiving the two-dose, 12-month regime; and one receiving the three-dose, 6-month regimen. In the former two cohorts, girls aged 9-14 years would receive their doses at 0 months and either 6 or 12 months, depending on the cohort. In the three-dose regimen, girls aged 15-25 years received doses at 0, 1, and 6 months. At enrollment, 550 girls were randomized into the two-dose, 6-month regimen; 415 girls into the two-dose, 12-month regimen; and 482 girls into the three-dose, 6-month regimen. Follow-up occurred at 1 month after they received the final dose for all three cohorts.

Ultimately, 534 girls in the two-dose, 6-month cohort; 394 in the two-dose, 12-month cohort; and 427 in the three-dose, 6-month cohort completed the study through the 1-month follow-up. Serologic testing indicated that girls in both the two-dose cohorts were not immunologically worse off than those who were in the three-dose cohort, with seroconversion differences of 0.00 when comparing HPV-16 and HPV-18 antibodies between any two of the three regimens. Furthermore, geometric mean antibody titer ratios for HPV-16 and HPV-18 were 1.09 (95% confidence interval, 0.97-1.22) and 0.85 (95% CI, 0.76-0.95) for the 6-month two-dose regimen vs. three-dose, and 0.89 (95% CI, 0.79-1.01) and 0.75 (95% CI, 0.67-0.85) for 12-month two-dose regimen vs.three-dose, indicating little statistically significant difference.

“The flexibility around the timing of the second dose, giving the option of annual vaccination over 2 consecutive years, is an added benefit [because] reduced dose schedules of HPV vaccines may facilitate vaccination implementation and reduce cost, allowing for higher vaccination coverage and potentially more girls being protected from cervical cancer,” the investigators noted.

The study was supported by GlaxoSmithKline Biologicals SA. Dr. Puthanakit received a grant from GSK through her institution. Some of her many coauthors disclosed relationships with GSK and/or other pharmaceutical companies.

[email protected]

“The licensed vaccines HPV-16/18 AS04–adjuvanted (Cervarix; GSK Vaccines) and HPV-6/11/16/18 (Gardasil; Merck) were first approved as regimen including three doses (3D) with administration over a 6-month period,” reported Thanyawee Puthanakit, MD, of Chulalongkorn University in Bangkok, and her associates. “Reduced dose schedules could make vaccination easier to implement and more affordable, creating the potential for higher vaccination coverage and improved cervical cancer protection (J Infect Dis. 2016;214:525-36).”

©jarun011/Thinkstock

The investigators enrolled girls aged 9-25 years starting in June 2011, from 33 clinical sites in Canada, Germany, Italy, Taiwan, and Thailand. The study lasted through January 2013, during which time 1,447 girls were enrolled and 1,428 were randomized into one of three cohorts: one receiving the two-dose, 6-month regimen; one receiving the two-dose, 12-month regime; and one receiving the three-dose, 6-month regimen. In the former two cohorts, girls aged 9-14 years would receive their doses at 0 months and either 6 or 12 months, depending on the cohort. In the three-dose regimen, girls aged 15-25 years received doses at 0, 1, and 6 months. At enrollment, 550 girls were randomized into the two-dose, 6-month regimen; 415 girls into the two-dose, 12-month regimen; and 482 girls into the three-dose, 6-month regimen. Follow-up occurred at 1 month after they received the final dose for all three cohorts.

Ultimately, 534 girls in the two-dose, 6-month cohort; 394 in the two-dose, 12-month cohort; and 427 in the three-dose, 6-month cohort completed the study through the 1-month follow-up. Serologic testing indicated that girls in both the two-dose cohorts were not immunologically worse off than those who were in the three-dose cohort, with seroconversion differences of 0.00 when comparing HPV-16 and HPV-18 antibodies between any two of the three regimens. Furthermore, geometric mean antibody titer ratios for HPV-16 and HPV-18 were 1.09 (95% confidence interval, 0.97-1.22) and 0.85 (95% CI, 0.76-0.95) for the 6-month two-dose regimen vs. three-dose, and 0.89 (95% CI, 0.79-1.01) and 0.75 (95% CI, 0.67-0.85) for 12-month two-dose regimen vs.three-dose, indicating little statistically significant difference.

“The flexibility around the timing of the second dose, giving the option of annual vaccination over 2 consecutive years, is an added benefit [because] reduced dose schedules of HPV vaccines may facilitate vaccination implementation and reduce cost, allowing for higher vaccination coverage and potentially more girls being protected from cervical cancer,” the investigators noted.

The study was supported by GlaxoSmithKline Biologicals SA. Dr. Puthanakit received a grant from GSK through her institution. Some of her many coauthors disclosed relationships with GSK and/or other pharmaceutical companies.

[email protected]

“The licensed vaccines HPV-16/18 AS04–adjuvanted (Cervarix; GSK Vaccines) and HPV-6/11/16/18 (Gardasil; Merck) were first approved as regimen including three doses (3D) with administration over a 6-month period,” reported Thanyawee Puthanakit, MD, of Chulalongkorn University in Bangkok, and her associates. “Reduced dose schedules could make vaccination easier to implement and more affordable, creating the potential for higher vaccination coverage and improved cervical cancer protection (J Infect Dis. 2016;214:525-36).”

©jarun011/Thinkstock

The investigators enrolled girls aged 9-25 years starting in June 2011, from 33 clinical sites in Canada, Germany, Italy, Taiwan, and Thailand. The study lasted through January 2013, during which time 1,447 girls were enrolled and 1,428 were randomized into one of three cohorts: one receiving the two-dose, 6-month regimen; one receiving the two-dose, 12-month regime; and one receiving the three-dose, 6-month regimen. In the former two cohorts, girls aged 9-14 years would receive their doses at 0 months and either 6 or 12 months, depending on the cohort. In the three-dose regimen, girls aged 15-25 years received doses at 0, 1, and 6 months. At enrollment, 550 girls were randomized into the two-dose, 6-month regimen; 415 girls into the two-dose, 12-month regimen; and 482 girls into the three-dose, 6-month regimen. Follow-up occurred at 1 month after they received the final dose for all three cohorts.

Ultimately, 534 girls in the two-dose, 6-month cohort; 394 in the two-dose, 12-month cohort; and 427 in the three-dose, 6-month cohort completed the study through the 1-month follow-up. Serologic testing indicated that girls in both the two-dose cohorts were not immunologically worse off than those who were in the three-dose cohort, with seroconversion differences of 0.00 when comparing HPV-16 and HPV-18 antibodies between any two of the three regimens. Furthermore, geometric mean antibody titer ratios for HPV-16 and HPV-18 were 1.09 (95% confidence interval, 0.97-1.22) and 0.85 (95% CI, 0.76-0.95) for the 6-month two-dose regimen vs. three-dose, and 0.89 (95% CI, 0.79-1.01) and 0.75 (95% CI, 0.67-0.85) for 12-month two-dose regimen vs.three-dose, indicating little statistically significant difference.

“The flexibility around the timing of the second dose, giving the option of annual vaccination over 2 consecutive years, is an added benefit [because] reduced dose schedules of HPV vaccines may facilitate vaccination implementation and reduce cost, allowing for higher vaccination coverage and potentially more girls being protected from cervical cancer,” the investigators noted.

The study was supported by GlaxoSmithKline Biologicals SA. Dr. Puthanakit received a grant from GSK through her institution. Some of her many coauthors disclosed relationships with GSK and/or other pharmaceutical companies.

[email protected]

SEATTLE – It’s better to place gastrostomy tubes before head and neck cancer surgery rather than after, according to a review of 184 patients.

The 73 patients in the study who got preoperative gastrostomy tubes (G-tubes) were sicker than the 111 who had G-tubes placed after surgery, with significantly higher American Society of Anesthesiologists scores, lower body mass indexes, and greater likelihoods of having both prior radiation and more extensive resections requiring flap reconstructions. They were, overall, a higher-risk population with a greater potential for bad outcomes, which is why tubes were placed preemptively.

Even so, at 6 months, the total average cost for the preop G-tube group was $39,751 versus $48,999 for the postoperative group, a savings of $9,248 per patient. The difference was driven by inpatient savings; the preop group left the hospital an average of 3.2 days sooner than their postop G-tube peers (9.4 days versus 12.6 days; P less than .001). Readmissions and other postdischarge costs were similar between the two groups, as were wound and nonwound complications.

“This data suggests that preoperative placement of G-tubes is associated with lower total health care costs. It appears there’s a potential for health care cost savings if candidates for G-tubes can be identified” before surgery and the tubes placed preoperatively, said investigator Joshua Waltonen, MD, of Wake Forest University, Winston-Salem, N.C.

That’s exactly what Wake Forest is doing now. Physicians there use a scoring system to determine how likely patients are to need G-tubes after surgery. If the risk is high, patients are counseled that putting one in beforehand is a good idea, he said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

The team previously found that risk factors include, among others, supracricoid laryngectomy, prior radiation, flap reconstruction, tracheostomy placement, and preop dysphagia and weight loss (JAMA Otolaryngol Head Neck Surg. 2014 Dec;140[12]:1198-206).

Two factors probably account for the shorter lengths of stay, Dr. Waltonen said. First, patients with preop feeding tubes go into surgery with a nutritional boost, which helps with recovery. Also, with a preop tube, patients don’t have to wait for general surgery to get around to placing one postoperatively.

Both groups were about 60 years old on average. The mean body mass index of the preop group was 23 kg/m^{2 and} 26 kg/m^{2 in the postop group} (P = .009). Almost two-thirds of preop patients had prior radiation versus a quarter of postop patients (P less than .001). Tumor and nodal stages were similar.

There was no outside funding for the work, and Dr. Waltonen had no disclosures.

[email protected]

SEATTLE – It’s better to place gastrostomy tubes before head and neck cancer surgery rather than after, according to a review of 184 patients.

The 73 patients in the study who got preoperative gastrostomy tubes (G-tubes) were sicker than the 111 who had G-tubes placed after surgery, with significantly higher American Society of Anesthesiologists scores, lower body mass indexes, and greater likelihoods of having both prior radiation and more extensive resections requiring flap reconstructions. They were, overall, a higher-risk population with a greater potential for bad outcomes, which is why tubes were placed preemptively.

Even so, at 6 months, the total average cost for the preop G-tube group was $39,751 versus $48,999 for the postoperative group, a savings of $9,248 per patient. The difference was driven by inpatient savings; the preop group left the hospital an average of 3.2 days sooner than their postop G-tube peers (9.4 days versus 12.6 days; P less than .001). Readmissions and other postdischarge costs were similar between the two groups, as were wound and nonwound complications.

“This data suggests that preoperative placement of G-tubes is associated with lower total health care costs. It appears there’s a potential for health care cost savings if candidates for G-tubes can be identified” before surgery and the tubes placed preoperatively, said investigator Joshua Waltonen, MD, of Wake Forest University, Winston-Salem, N.C.

That’s exactly what Wake Forest is doing now. Physicians there use a scoring system to determine how likely patients are to need G-tubes after surgery. If the risk is high, patients are counseled that putting one in beforehand is a good idea, he said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

The team previously found that risk factors include, among others, supracricoid laryngectomy, prior radiation, flap reconstruction, tracheostomy placement, and preop dysphagia and weight loss (JAMA Otolaryngol Head Neck Surg. 2014 Dec;140[12]:1198-206).

Two factors probably account for the shorter lengths of stay, Dr. Waltonen said. First, patients with preop feeding tubes go into surgery with a nutritional boost, which helps with recovery. Also, with a preop tube, patients don’t have to wait for general surgery to get around to placing one postoperatively.

Both groups were about 60 years old on average. The mean body mass index of the preop group was 23 kg/m^{2 and} 26 kg/m^{2 in the postop group} (P = .009). Almost two-thirds of preop patients had prior radiation versus a quarter of postop patients (P less than .001). Tumor and nodal stages were similar.

There was no outside funding for the work, and Dr. Waltonen had no disclosures.

[email protected]

SEATTLE – It’s better to place gastrostomy tubes before head and neck cancer surgery rather than after, according to a review of 184 patients.

The 73 patients in the study who got preoperative gastrostomy tubes (G-tubes) were sicker than the 111 who had G-tubes placed after surgery, with significantly higher American Society of Anesthesiologists scores, lower body mass indexes, and greater likelihoods of having both prior radiation and more extensive resections requiring flap reconstructions. They were, overall, a higher-risk population with a greater potential for bad outcomes, which is why tubes were placed preemptively.

Even so, at 6 months, the total average cost for the preop G-tube group was $39,751 versus $48,999 for the postoperative group, a savings of $9,248 per patient. The difference was driven by inpatient savings; the preop group left the hospital an average of 3.2 days sooner than their postop G-tube peers (9.4 days versus 12.6 days; P less than .001). Readmissions and other postdischarge costs were similar between the two groups, as were wound and nonwound complications.

“This data suggests that preoperative placement of G-tubes is associated with lower total health care costs. It appears there’s a potential for health care cost savings if candidates for G-tubes can be identified” before surgery and the tubes placed preoperatively, said investigator Joshua Waltonen, MD, of Wake Forest University, Winston-Salem, N.C.

That’s exactly what Wake Forest is doing now. Physicians there use a scoring system to determine how likely patients are to need G-tubes after surgery. If the risk is high, patients are counseled that putting one in beforehand is a good idea, he said at the International Conference on Head and Neck Cancer, held by the American Head and Neck Society.

The team previously found that risk factors include, among others, supracricoid laryngectomy, prior radiation, flap reconstruction, tracheostomy placement, and preop dysphagia and weight loss (JAMA Otolaryngol Head Neck Surg. 2014 Dec;140[12]:1198-206).

Two factors probably account for the shorter lengths of stay, Dr. Waltonen said. First, patients with preop feeding tubes go into surgery with a nutritional boost, which helps with recovery. Also, with a preop tube, patients don’t have to wait for general surgery to get around to placing one postoperatively.

Both groups were about 60 years old on average. The mean body mass index of the preop group was 23 kg/m^{2 and} 26 kg/m^{2 in the postop group} (P = .009). Almost two-thirds of preop patients had prior radiation versus a quarter of postop patients (P less than .001). Tumor and nodal stages were similar.

There was no outside funding for the work, and Dr. Waltonen had no disclosures.

[email protected]