Adding daratumumab to bortezomib (a protease inhibitor [PI]) and dexamethasone reduces the risk of disease progression or death by 61% in patients with multiple myeloma (MM), compared with bortezomib and dexamethasone alone, according to an interim analysis of phase 3 trial results.

Related: Multiple Myeloma: Updates on Diagnosis and Management

Daratumumab is a biologic that targets CD38, a surface protein that is highly expressed across MM cells, regardless of disease stage. “CD38 is the most important tumor antigen on myeloma plasma cells,” said Antonio Palumbo, MD, University of Torino, Italy, who presented the study findings at the 2016 American Society of Clinical Oncology Annual Meeting in June. Daratumumab has more than 1 immune-mediated mechanism of action and both direct and indirect antimyeloma activity: It depletes CD38+ immunosuppressive regulatory cells and promotes T-cell expansion and activation, all while directly killing myeloma cells.

The multinational study (CASTOR) included 498 patients with MM who had received a median of 2 prior lines of therapy: bortezomib, an immunomodulatory agent, or a PI and immunomodulatory agent. Prior treatments had been unsuccessful in one-third of patients. In this study, researchers randomly assigned 251 patients to combination treatment with daratumumab.

Related: Treating Patients With Multiple Myeloma in the VA

Daratumumab significantly increased the overall response rate (83% vs 63%) and doubled rates of complete response or better (19% vs 9%). It also doubled the rates of very good partial response (59% vs 29%). The combination therapy met the primary endpoint of improved progression-free survival at a median follow-up of 7.4 months (60.7% in the combination arm, compared with 26.9%). The treatment was unblinded after meeting the primary endpoint.

The treatment benefits of the combination regimen were maintained across clinically relevant subgroups, the researchers said. The most common adverse effects were thrombocytopenia ,sensory peripheral neuropathy, anaemia, and diarrhea.

“These compelling phase 3 results demonstrate that a regimen built on daratumumab deepens clinical responses and help to underscore its potential for multiple myeloma patients who have been previously treated,” said Dr. Palumbo.

Related: A Mysterious Massive Hemorrhage

In a discussion of the study, Paul Richardson, MD, of the Dana-Farber Cancer Institute, praised the study as “outstanding” and “potentially practice changing.” However, another panel member noted that with an added cost of more than $10,000 a month, the treatment could be out of reach for many.

Adding daratumumab to bortezomib (a protease inhibitor [PI]) and dexamethasone reduces the risk of disease progression or death by 61% in patients with multiple myeloma (MM), compared with bortezomib and dexamethasone alone, according to an interim analysis of phase 3 trial results.

Related: Multiple Myeloma: Updates on Diagnosis and Management

Daratumumab is a biologic that targets CD38, a surface protein that is highly expressed across MM cells, regardless of disease stage. “CD38 is the most important tumor antigen on myeloma plasma cells,” said Antonio Palumbo, MD, University of Torino, Italy, who presented the study findings at the 2016 American Society of Clinical Oncology Annual Meeting in June. Daratumumab has more than 1 immune-mediated mechanism of action and both direct and indirect antimyeloma activity: It depletes CD38+ immunosuppressive regulatory cells and promotes T-cell expansion and activation, all while directly killing myeloma cells.

The multinational study (CASTOR) included 498 patients with MM who had received a median of 2 prior lines of therapy: bortezomib, an immunomodulatory agent, or a PI and immunomodulatory agent. Prior treatments had been unsuccessful in one-third of patients. In this study, researchers randomly assigned 251 patients to combination treatment with daratumumab.

Related: Treating Patients With Multiple Myeloma in the VA

Daratumumab significantly increased the overall response rate (83% vs 63%) and doubled rates of complete response or better (19% vs 9%). It also doubled the rates of very good partial response (59% vs 29%). The combination therapy met the primary endpoint of improved progression-free survival at a median follow-up of 7.4 months (60.7% in the combination arm, compared with 26.9%). The treatment was unblinded after meeting the primary endpoint.

The treatment benefits of the combination regimen were maintained across clinically relevant subgroups, the researchers said. The most common adverse effects were thrombocytopenia ,sensory peripheral neuropathy, anaemia, and diarrhea.

“These compelling phase 3 results demonstrate that a regimen built on daratumumab deepens clinical responses and help to underscore its potential for multiple myeloma patients who have been previously treated,” said Dr. Palumbo.

Related: A Mysterious Massive Hemorrhage

In a discussion of the study, Paul Richardson, MD, of the Dana-Farber Cancer Institute, praised the study as “outstanding” and “potentially practice changing.” However, another panel member noted that with an added cost of more than $10,000 a month, the treatment could be out of reach for many.

Adding daratumumab to bortezomib (a protease inhibitor [PI]) and dexamethasone reduces the risk of disease progression or death by 61% in patients with multiple myeloma (MM), compared with bortezomib and dexamethasone alone, according to an interim analysis of phase 3 trial results.

Related: Multiple Myeloma: Updates on Diagnosis and Management

Daratumumab is a biologic that targets CD38, a surface protein that is highly expressed across MM cells, regardless of disease stage. “CD38 is the most important tumor antigen on myeloma plasma cells,” said Antonio Palumbo, MD, University of Torino, Italy, who presented the study findings at the 2016 American Society of Clinical Oncology Annual Meeting in June. Daratumumab has more than 1 immune-mediated mechanism of action and both direct and indirect antimyeloma activity: It depletes CD38+ immunosuppressive regulatory cells and promotes T-cell expansion and activation, all while directly killing myeloma cells.

The multinational study (CASTOR) included 498 patients with MM who had received a median of 2 prior lines of therapy: bortezomib, an immunomodulatory agent, or a PI and immunomodulatory agent. Prior treatments had been unsuccessful in one-third of patients. In this study, researchers randomly assigned 251 patients to combination treatment with daratumumab.

Related: Treating Patients With Multiple Myeloma in the VA

Daratumumab significantly increased the overall response rate (83% vs 63%) and doubled rates of complete response or better (19% vs 9%). It also doubled the rates of very good partial response (59% vs 29%). The combination therapy met the primary endpoint of improved progression-free survival at a median follow-up of 7.4 months (60.7% in the combination arm, compared with 26.9%). The treatment was unblinded after meeting the primary endpoint.

The treatment benefits of the combination regimen were maintained across clinically relevant subgroups, the researchers said. The most common adverse effects were thrombocytopenia ,sensory peripheral neuropathy, anaemia, and diarrhea.

“These compelling phase 3 results demonstrate that a regimen built on daratumumab deepens clinical responses and help to underscore its potential for multiple myeloma patients who have been previously treated,” said Dr. Palumbo.

Related: A Mysterious Massive Hemorrhage

In a discussion of the study, Paul Richardson, MD, of the Dana-Farber Cancer Institute, praised the study as “outstanding” and “potentially practice changing.” However, another panel member noted that with an added cost of more than $10,000 a month, the treatment could be out of reach for many.

Ensuring patients have a realistic expectation of cosmetic procedures starts with good communication between the physician and patient. Dr. Emmy Graber describes how to have a happy patient and focuses on conversations with patients regarding downtime, side effects, and treatment results. She also addresses the financial consequences of cosmetic procedures.

Ensuring patients have a realistic expectation of cosmetic procedures starts with good communication between the physician and patient. Dr. Emmy Graber describes how to have a happy patient and focuses on conversations with patients regarding downtime, side effects, and treatment results. She also addresses the financial consequences of cosmetic procedures.

Ensuring patients have a realistic expectation of cosmetic procedures starts with good communication between the physician and patient. Dr. Emmy Graber describes how to have a happy patient and focuses on conversations with patients regarding downtime, side effects, and treatment results. She also addresses the financial consequences of cosmetic procedures.

Learn more by visiting www.hospitalmedicine.org/BOOST and clicking on “BOOST Results” to read the full case study.

Learn more by visiting www.hospitalmedicine.org/BOOST and clicking on “BOOST Results” to read the full case study.

Learn more by visiting www.hospitalmedicine.org/BOOST and clicking on “BOOST Results” to read the full case study.

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.

Warfarin tablets

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.

Warfarin tablets

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.

Warfarin tablets

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.

The microfluidic device

Photo courtesy of the

Wyss Institute at Harvard

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.”

The microfluidic device

Photo courtesy of the

Wyss Institute at Harvard

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.”

The microfluidic device

Photo courtesy of the

Wyss Institute at Harvard

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.”

Anopheles gambiae mosquito

Photo courtesy of the CDC

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.

Anopheles gambiae mosquito

Photo courtesy of the CDC

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.

Anopheles gambiae mosquito

Photo courtesy of the CDC

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.

Red blood cells from a mouse

with sickle cell anemia

Image courtesy of the

University of Michigan

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.”

Red blood cells from a mouse

with sickle cell anemia

Image courtesy of the

University of Michigan

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.”

Red blood cells from a mouse

with sickle cell anemia

Image courtesy of the

University of Michigan

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]