The presence of competing risks and overall lower levels of provider proficiency appeared to limit the benefits of carotid artery stenting in Medicare beneficiaries, according to the results of a large retrospective cohort study of the Centers for Medicare & Medicaid Services CAS database (2005-2009).

Periprocedural mortality was more than twice the rate in this patient population than in those earlier patients those involved in the pivotal CREST and SAPPHIRE clinical trials, according to a report published online Jan. 12 in JAMA Neurology [doi:10.1001/jamaneurol.2014.3638].

“The higher risk of periprocedural complications and the burden of competing risks owing to age and comorbidity burden must be carefully considered when deciding between carotid stenosis treatments for Medicare beneficiaries,” according to Jessica J. Jalbert, Ph.D., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her colleagues.

Over 22,000 patients were assessed in the study. The mean patient age was just over 76 years, 60.5% were men, and 94% were white. Approximately half were symptomatic, 91.2% were at high surgical risk, and 97.4% had carotid stenosis of at least 70%.

Almost 80% of the patients undergoing carotid artery stenting (CAS) met the SAPPHIRE trial indications and about half met at least one of the SAPPHIRE criteria for high surgical risk.

In the mean follow-up of approximately 2 years, mortality risks exceeded one-third for patients who were 80 years of age or older (41.5% mortality risk), symptomatic (37.3% risk), at high surgical risk with symptomatic carotid stenosis of at least 50% (37.3% risk), or admitted nonelectively (36.2% risk). In addition, among asymptomatic patients, mortality after the periprocedural period exceeded one-third for patients at least 80 years old.

Of particular concern, few of these Medicare beneficiaries undergoing CAS as per the National Coverage Determinations were treated by providers with proficiency levels similar to those required in the clinical trials. This is a potential problem because lower annual volume and early operator experience are associated with increased periprocedural mortality, the authors wrote.

CAS was performed primarily by male physicians (98.4%), specializing in cardiology (52.9%), practicing within a group (79.4%), and residing in the South (42.5%). The mean number of past-year CAS procedures performed was only 13.9 for physicians and 29.8 for hospitals. This translated to more than 80% of the physicians not meeting the minimum CAS volume requirements and/or minimum complication rates of the SAPPHIRE trial, and more than 90% not meeting the requirements of the CREST trial.

“Our results may support concerns about the limited generalizability of [randomized clinical trial] findings,” the researchers stated.

“Real-world observational studies comparing CAS, carotid endarterectomy, and medical management are needed to determine the performance of carotid stenosis treatment options for Medicare beneficiaries,” Dr. Jalbert and her colleagues concluded.

The authors reported no relevant disclosures. The study was funded by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services.

[email protected]

The presence of competing risks and overall lower levels of provider proficiency appeared to limit the benefits of carotid artery stenting in Medicare beneficiaries, according to the results of a large retrospective cohort study of the Centers for Medicare & Medicaid Services CAS database (2005-2009).

Periprocedural mortality was more than twice the rate in this patient population than in those earlier patients those involved in the pivotal CREST and SAPPHIRE clinical trials, according to a report published online Jan. 12 in JAMA Neurology [doi:10.1001/jamaneurol.2014.3638].

“The higher risk of periprocedural complications and the burden of competing risks owing to age and comorbidity burden must be carefully considered when deciding between carotid stenosis treatments for Medicare beneficiaries,” according to Jessica J. Jalbert, Ph.D., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her colleagues.

Over 22,000 patients were assessed in the study. The mean patient age was just over 76 years, 60.5% were men, and 94% were white. Approximately half were symptomatic, 91.2% were at high surgical risk, and 97.4% had carotid stenosis of at least 70%.

Almost 80% of the patients undergoing carotid artery stenting (CAS) met the SAPPHIRE trial indications and about half met at least one of the SAPPHIRE criteria for high surgical risk.

In the mean follow-up of approximately 2 years, mortality risks exceeded one-third for patients who were 80 years of age or older (41.5% mortality risk), symptomatic (37.3% risk), at high surgical risk with symptomatic carotid stenosis of at least 50% (37.3% risk), or admitted nonelectively (36.2% risk). In addition, among asymptomatic patients, mortality after the periprocedural period exceeded one-third for patients at least 80 years old.

Of particular concern, few of these Medicare beneficiaries undergoing CAS as per the National Coverage Determinations were treated by providers with proficiency levels similar to those required in the clinical trials. This is a potential problem because lower annual volume and early operator experience are associated with increased periprocedural mortality, the authors wrote.

CAS was performed primarily by male physicians (98.4%), specializing in cardiology (52.9%), practicing within a group (79.4%), and residing in the South (42.5%). The mean number of past-year CAS procedures performed was only 13.9 for physicians and 29.8 for hospitals. This translated to more than 80% of the physicians not meeting the minimum CAS volume requirements and/or minimum complication rates of the SAPPHIRE trial, and more than 90% not meeting the requirements of the CREST trial.

“Our results may support concerns about the limited generalizability of [randomized clinical trial] findings,” the researchers stated.

“Real-world observational studies comparing CAS, carotid endarterectomy, and medical management are needed to determine the performance of carotid stenosis treatment options for Medicare beneficiaries,” Dr. Jalbert and her colleagues concluded.

The authors reported no relevant disclosures. The study was funded by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services.

[email protected]

The presence of competing risks and overall lower levels of provider proficiency appeared to limit the benefits of carotid artery stenting in Medicare beneficiaries, according to the results of a large retrospective cohort study of the Centers for Medicare & Medicaid Services CAS database (2005-2009).

Periprocedural mortality was more than twice the rate in this patient population than in those earlier patients those involved in the pivotal CREST and SAPPHIRE clinical trials, according to a report published online Jan. 12 in JAMA Neurology [doi:10.1001/jamaneurol.2014.3638].

“The higher risk of periprocedural complications and the burden of competing risks owing to age and comorbidity burden must be carefully considered when deciding between carotid stenosis treatments for Medicare beneficiaries,” according to Jessica J. Jalbert, Ph.D., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her colleagues.

Over 22,000 patients were assessed in the study. The mean patient age was just over 76 years, 60.5% were men, and 94% were white. Approximately half were symptomatic, 91.2% were at high surgical risk, and 97.4% had carotid stenosis of at least 70%.

Almost 80% of the patients undergoing carotid artery stenting (CAS) met the SAPPHIRE trial indications and about half met at least one of the SAPPHIRE criteria for high surgical risk.

In the mean follow-up of approximately 2 years, mortality risks exceeded one-third for patients who were 80 years of age or older (41.5% mortality risk), symptomatic (37.3% risk), at high surgical risk with symptomatic carotid stenosis of at least 50% (37.3% risk), or admitted nonelectively (36.2% risk). In addition, among asymptomatic patients, mortality after the periprocedural period exceeded one-third for patients at least 80 years old.

Of particular concern, few of these Medicare beneficiaries undergoing CAS as per the National Coverage Determinations were treated by providers with proficiency levels similar to those required in the clinical trials. This is a potential problem because lower annual volume and early operator experience are associated with increased periprocedural mortality, the authors wrote.

CAS was performed primarily by male physicians (98.4%), specializing in cardiology (52.9%), practicing within a group (79.4%), and residing in the South (42.5%). The mean number of past-year CAS procedures performed was only 13.9 for physicians and 29.8 for hospitals. This translated to more than 80% of the physicians not meeting the minimum CAS volume requirements and/or minimum complication rates of the SAPPHIRE trial, and more than 90% not meeting the requirements of the CREST trial.

“Our results may support concerns about the limited generalizability of [randomized clinical trial] findings,” the researchers stated.

“Real-world observational studies comparing CAS, carotid endarterectomy, and medical management are needed to determine the performance of carotid stenosis treatment options for Medicare beneficiaries,” Dr. Jalbert and her colleagues concluded.

The authors reported no relevant disclosures. The study was funded by the Agency for Healthcare Research and Quality, U.S. Department of Health & Human Services.

[email protected]

SAN FRANCISCO—MicroRNA-155 (miR-155) can act as an oncogenic driver in ALK− anaplastic large-cell lymphoma (ALCL) and may therefore be a therapeutic target for the disease, according to a presentation at the 7th Annual T-cell Lymphoma Forum.

Analyzing patient samples and cell lines, researchers discovered that miR-155 is highly expressed in ALK− ALCL but is nearly absent in ALK+ ALCL.

They also found evidence suggesting that miR-155 drives tumor growth in mouse models of ALK− ALCL.

Philipp Staber, MD, PhD, of the Medical University of Vienna in Austria, presented these findings at the meeting.

Dr Staber and his colleagues previously found (Merkel et al, PNAS 2010) that miR-155 was highly expressed in ALK− ALCL. So they decided to take a closer look at the phenomenon.

They assessed miR-155 expression in samples from patients with ALK+ or ALK− ALCL, as well as 6 ALCL cell lines.

miR-155 expression was significantly higher in the ALK− patient samples than in the ALK+ samples (P<0.001). And it was significantly higher (P<0.001) in the ALK− cell lines (DL-40, Mac1, and Mac2a) than in the ALK+ cell lines (K299, SR789, and SUP-M2).

Dr Staber and his colleagues then overexpressed miR-155 in ALK+ ALCL cell lines (K299 and SR789). And they observed a decrease in known target genes of miR-155—C/EBPβ, SOCS1, and SHIP1.

The researchers also observed an inverse correlation between miR-155 host gene promoter methylation and miR-155 expression in an ALCL+ cell line, which suggested that ALK activity has no direct effect on miR-155 levels.

The team treated the K299 cell line with the ALK inhibitor crizotinib at 100 nM, 200 nM, and 400 nM doses and found that miR-155 did not increase at any dose. Dr Staber noted, however, that the researchers were only able to treat cells for a maximum of 24 hours.

The group then discovered that anti-miR-155 mimics could reduce tumor growth in mouse models of ALK- ALCL. Mice were injected with Mac1 or Mac2a cells transfected with anti-miR-155, control RNA, or pre-miR-155 oligos.

In both Mac1 and Mac2 models, tumors were substantially smaller in the anti-mir-155 mice than in the pre-miR-155 mice (P=0.038 and P=0.006, respectively). But tumor growth was not significantly reduced compared to controls.

“Immunohistochemistry in these tumors shows quite a clear picture,” Dr Staber said. “The C/EBPβ target gene is overexpressed when using anti-miR-155, and [expression is decreased] with overexpression of miR-155. And the same is true for SOCS1. STAT3 signaling is increased through overexpression of miR-155.”

The researchers observed the same effect in ALK− ALCL patient samples.

Using ALK+ cell lines (K299 and SR789), the team went on to show that miR-155 suppresses IL-8 expression and induces IL-22 expression, a finding they verified in mice.

“IL-8 is a direct target of C/EBPβ, and C/EBPβ, as shown before, is a target of miR-155, so this makes sense,” Dr Staber said. “On the other hand, IL-22 is a strong inducer of STAT3 signaling, which is strongly induced when we increase miR-155 expression.”

Dr Staber and his colleagues concluded that these findings, when taken together, suggest that miR-155 could be a therapeutic target for ALK− ALCL.

SAN FRANCISCO—MicroRNA-155 (miR-155) can act as an oncogenic driver in ALK− anaplastic large-cell lymphoma (ALCL) and may therefore be a therapeutic target for the disease, according to a presentation at the 7th Annual T-cell Lymphoma Forum.

Analyzing patient samples and cell lines, researchers discovered that miR-155 is highly expressed in ALK− ALCL but is nearly absent in ALK+ ALCL.

They also found evidence suggesting that miR-155 drives tumor growth in mouse models of ALK− ALCL.

Philipp Staber, MD, PhD, of the Medical University of Vienna in Austria, presented these findings at the meeting.

Dr Staber and his colleagues previously found (Merkel et al, PNAS 2010) that miR-155 was highly expressed in ALK− ALCL. So they decided to take a closer look at the phenomenon.

They assessed miR-155 expression in samples from patients with ALK+ or ALK− ALCL, as well as 6 ALCL cell lines.

miR-155 expression was significantly higher in the ALK− patient samples than in the ALK+ samples (P<0.001). And it was significantly higher (P<0.001) in the ALK− cell lines (DL-40, Mac1, and Mac2a) than in the ALK+ cell lines (K299, SR789, and SUP-M2).

Dr Staber and his colleagues then overexpressed miR-155 in ALK+ ALCL cell lines (K299 and SR789). And they observed a decrease in known target genes of miR-155—C/EBPβ, SOCS1, and SHIP1.

The researchers also observed an inverse correlation between miR-155 host gene promoter methylation and miR-155 expression in an ALCL+ cell line, which suggested that ALK activity has no direct effect on miR-155 levels.

The team treated the K299 cell line with the ALK inhibitor crizotinib at 100 nM, 200 nM, and 400 nM doses and found that miR-155 did not increase at any dose. Dr Staber noted, however, that the researchers were only able to treat cells for a maximum of 24 hours.

The group then discovered that anti-miR-155 mimics could reduce tumor growth in mouse models of ALK- ALCL. Mice were injected with Mac1 or Mac2a cells transfected with anti-miR-155, control RNA, or pre-miR-155 oligos.

In both Mac1 and Mac2 models, tumors were substantially smaller in the anti-mir-155 mice than in the pre-miR-155 mice (P=0.038 and P=0.006, respectively). But tumor growth was not significantly reduced compared to controls.

“Immunohistochemistry in these tumors shows quite a clear picture,” Dr Staber said. “The C/EBPβ target gene is overexpressed when using anti-miR-155, and [expression is decreased] with overexpression of miR-155. And the same is true for SOCS1. STAT3 signaling is increased through overexpression of miR-155.”

The researchers observed the same effect in ALK− ALCL patient samples.

Using ALK+ cell lines (K299 and SR789), the team went on to show that miR-155 suppresses IL-8 expression and induces IL-22 expression, a finding they verified in mice.

“IL-8 is a direct target of C/EBPβ, and C/EBPβ, as shown before, is a target of miR-155, so this makes sense,” Dr Staber said. “On the other hand, IL-22 is a strong inducer of STAT3 signaling, which is strongly induced when we increase miR-155 expression.”

Dr Staber and his colleagues concluded that these findings, when taken together, suggest that miR-155 could be a therapeutic target for ALK− ALCL.

SAN FRANCISCO—MicroRNA-155 (miR-155) can act as an oncogenic driver in ALK− anaplastic large-cell lymphoma (ALCL) and may therefore be a therapeutic target for the disease, according to a presentation at the 7th Annual T-cell Lymphoma Forum.

Analyzing patient samples and cell lines, researchers discovered that miR-155 is highly expressed in ALK− ALCL but is nearly absent in ALK+ ALCL.

They also found evidence suggesting that miR-155 drives tumor growth in mouse models of ALK− ALCL.

Philipp Staber, MD, PhD, of the Medical University of Vienna in Austria, presented these findings at the meeting.

Dr Staber and his colleagues previously found (Merkel et al, PNAS 2010) that miR-155 was highly expressed in ALK− ALCL. So they decided to take a closer look at the phenomenon.

They assessed miR-155 expression in samples from patients with ALK+ or ALK− ALCL, as well as 6 ALCL cell lines.

miR-155 expression was significantly higher in the ALK− patient samples than in the ALK+ samples (P<0.001). And it was significantly higher (P<0.001) in the ALK− cell lines (DL-40, Mac1, and Mac2a) than in the ALK+ cell lines (K299, SR789, and SUP-M2).

Dr Staber and his colleagues then overexpressed miR-155 in ALK+ ALCL cell lines (K299 and SR789). And they observed a decrease in known target genes of miR-155—C/EBPβ, SOCS1, and SHIP1.

The researchers also observed an inverse correlation between miR-155 host gene promoter methylation and miR-155 expression in an ALCL+ cell line, which suggested that ALK activity has no direct effect on miR-155 levels.

The team treated the K299 cell line with the ALK inhibitor crizotinib at 100 nM, 200 nM, and 400 nM doses and found that miR-155 did not increase at any dose. Dr Staber noted, however, that the researchers were only able to treat cells for a maximum of 24 hours.

The group then discovered that anti-miR-155 mimics could reduce tumor growth in mouse models of ALK- ALCL. Mice were injected with Mac1 or Mac2a cells transfected with anti-miR-155, control RNA, or pre-miR-155 oligos.

In both Mac1 and Mac2 models, tumors were substantially smaller in the anti-mir-155 mice than in the pre-miR-155 mice (P=0.038 and P=0.006, respectively). But tumor growth was not significantly reduced compared to controls.

“Immunohistochemistry in these tumors shows quite a clear picture,” Dr Staber said. “The C/EBPβ target gene is overexpressed when using anti-miR-155, and [expression is decreased] with overexpression of miR-155. And the same is true for SOCS1. STAT3 signaling is increased through overexpression of miR-155.”

The researchers observed the same effect in ALK− ALCL patient samples.

Using ALK+ cell lines (K299 and SR789), the team went on to show that miR-155 suppresses IL-8 expression and induces IL-22 expression, a finding they verified in mice.

“IL-8 is a direct target of C/EBPβ, and C/EBPβ, as shown before, is a target of miR-155, so this makes sense,” Dr Staber said. “On the other hand, IL-22 is a strong inducer of STAT3 signaling, which is strongly induced when we increase miR-155 expression.”

Dr Staber and his colleagues concluded that these findings, when taken together, suggest that miR-155 could be a therapeutic target for ALK− ALCL.

Transplanting a small number of antiviral memory T cells along with donor hematopoietic stem cells can fight and may even prevent cytomegalovirus (CMV) disease in transplant recipients, according to preclinical research published in the Journal of Immunology.

To date, researchers have focused on developing anti-CMV immunotherapy with effector-phenotype CD8⁺ T cells (T_EFF cells), which attack and kill virally infected host cells.

But Christopher Snyder, PhD, of Thomas Jefferson University in Philadelphia, Pennsylvania, and his colleagues found that CMV-specific T_EFF cells divide poorly in response to CMV infection or reactivation in mouse models.

So they wondered if CMV-specific memory-phenotype CD8⁺ T cells (T_M cells)—which act more like stem cells—could help control the infection long-term.

The group showed that a small number of T_M cells were enough to produce and repeatedly replenish all of the T_EFF cells needed to fight CMV.

The infused T_M cells became major contributors to the recipient antiviral immune response, persisting for at least 3 months’ time and producing T_EFF cells at a steady stream.

To determine whether these cells have counterparts in humans, Dr Snyder and his colleagues compared the genomic fingerprints of mouse and human T_M cells that were specific for CMV. Results showed the two had similar profiles.

“This suggested that human and mouse CMV-specific memory T cells are very similar populations,” said study author Michael Quinn, an MD/PhD student at Thomas Jefferson University.

“Therefore, infusing similar cells into humans could improve on immunotherapeutic methods for controlling CMV infection. This may be a valuable approach to keep the disease from emerging in people.”

Dr Snyder added, “Our data argue for developing new clinical trials focused specifically on using these T memory cells, in order to determine if it would indeed be better than current therapeutic options.”

Transplanting a small number of antiviral memory T cells along with donor hematopoietic stem cells can fight and may even prevent cytomegalovirus (CMV) disease in transplant recipients, according to preclinical research published in the Journal of Immunology.

To date, researchers have focused on developing anti-CMV immunotherapy with effector-phenotype CD8⁺ T cells (T_EFF cells), which attack and kill virally infected host cells.

But Christopher Snyder, PhD, of Thomas Jefferson University in Philadelphia, Pennsylvania, and his colleagues found that CMV-specific T_EFF cells divide poorly in response to CMV infection or reactivation in mouse models.

So they wondered if CMV-specific memory-phenotype CD8⁺ T cells (T_M cells)—which act more like stem cells—could help control the infection long-term.

The group showed that a small number of T_M cells were enough to produce and repeatedly replenish all of the T_EFF cells needed to fight CMV.

The infused T_M cells became major contributors to the recipient antiviral immune response, persisting for at least 3 months’ time and producing T_EFF cells at a steady stream.

To determine whether these cells have counterparts in humans, Dr Snyder and his colleagues compared the genomic fingerprints of mouse and human T_M cells that were specific for CMV. Results showed the two had similar profiles.

“This suggested that human and mouse CMV-specific memory T cells are very similar populations,” said study author Michael Quinn, an MD/PhD student at Thomas Jefferson University.

“Therefore, infusing similar cells into humans could improve on immunotherapeutic methods for controlling CMV infection. This may be a valuable approach to keep the disease from emerging in people.”

Dr Snyder added, “Our data argue for developing new clinical trials focused specifically on using these T memory cells, in order to determine if it would indeed be better than current therapeutic options.”

Transplanting a small number of antiviral memory T cells along with donor hematopoietic stem cells can fight and may even prevent cytomegalovirus (CMV) disease in transplant recipients, according to preclinical research published in the Journal of Immunology.

To date, researchers have focused on developing anti-CMV immunotherapy with effector-phenotype CD8⁺ T cells (T_EFF cells), which attack and kill virally infected host cells.

But Christopher Snyder, PhD, of Thomas Jefferson University in Philadelphia, Pennsylvania, and his colleagues found that CMV-specific T_EFF cells divide poorly in response to CMV infection or reactivation in mouse models.

So they wondered if CMV-specific memory-phenotype CD8⁺ T cells (T_M cells)—which act more like stem cells—could help control the infection long-term.

The group showed that a small number of T_M cells were enough to produce and repeatedly replenish all of the T_EFF cells needed to fight CMV.

The infused T_M cells became major contributors to the recipient antiviral immune response, persisting for at least 3 months’ time and producing T_EFF cells at a steady stream.

To determine whether these cells have counterparts in humans, Dr Snyder and his colleagues compared the genomic fingerprints of mouse and human T_M cells that were specific for CMV. Results showed the two had similar profiles.

“This suggested that human and mouse CMV-specific memory T cells are very similar populations,” said study author Michael Quinn, an MD/PhD student at Thomas Jefferson University.

“Therefore, infusing similar cells into humans could improve on immunotherapeutic methods for controlling CMV infection. This may be a valuable approach to keep the disease from emerging in people.”

Dr Snyder added, “Our data argue for developing new clinical trials focused specifically on using these T memory cells, in order to determine if it would indeed be better than current therapeutic options.”

The monoclonal IgM antibody PAT-SM6 was “well-tolerated” and showed “modest clinical activity” in patients with relapsed or refractory multiple myeloma (MM), researchers reported in haematologica.

Adverse events occurred in all 12 patients enrolled in the phase 1/2a study, but most were considered unrelated to treatment.

A third of patients, all of whom had progressive disease upon study entry, achieved stable disease after receiving PAT-SM6. The remaining patients progressed.

Leo Rasche, MD, of University Hospital Wurzburg in Germany, and his colleagues conducted this study. It was funded, in part, by Patrys Limited, the company developing PAT-SM6.

The study included 12 heavily pretreated MM patients. They had a median age of 69.5 years and a long-standing history of MM (range, 3.25 to 15.75 years). They had received a median of 3.9 prior lines of therapy (range, 2-7).

Patients received 4 escalating doses of PAT-SM6, over a period of 2 weeks, via intravenous infusions at 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 6 mg/kg.

Safety data

There were 54 treatment-emergent adverse events in all 12 patients. However, there were no dose-limiting toxicities and no deaths. The maximum tolerated dose has not been reached.

More than 80% of the adverse events were of mild to moderate intensity. Two patients (16.6%) each experienced a single serious event. One patient had acute back pain, and one had a bile duct stone. Neither of these events was considered treatment-related.

Twenty-one adverse events were considered treatment-related. This included leukopenia (66.6%), neutropenia (50%), hypertension (16.6%), catheter-related thrombophlebitis (8.3%), injection site erythema (8.3%), slight headache (8.3%), C-reactive protein increase (8.3%), and hypertriglyceridemia (8.3%).

Efficacy data

Most patients progressed following treatment, but 4 (33.3%) had stable disease. The investigators noted that stable disease is not necessarily connected with a clinical benefit, so they analyzed the 4 patients in detail.

Patient 4, who received PAT-SM6 at 1 mg/kg, entered the study with high-risk disease. The patient had 13q deletion and 1q21 gain, had received 5 prior lines of therapy, and was refractory to novel agents, including pomalidomide and bortezomib.

The patient was treatment-free for 1 month prior to receiving PAT-SM6. During treatment, there were no symptoms of active myeloma, and the patient asked to continue salvage therapy 1 week after the end of the study.

Patient 7, who received PAT-SM6 at 3 mg/kg, had been diagnosed with MM for 15 years and had received 4 prior lines of therapy.

The patient’s treatment-free interval before receiving PAT-SM6 was 30 months. After PAT-SM6, the patient was therapy-free for 4.6 months.

Patient 10, who received PAT-SM6 at 6mg/kg, had 6 prior lines of therapy, including tandem autologous stem cell transplant and several polychemotherapeutic regimens.

The patient was therapy-free for 4 months prior to receiving PAT-SM6. The patient requested salvage therapy 1 month after receiving PAT-SM6.

Patient 11, who received PAT-SM6 at 6mg/kg, had 4 prior lines of therapy and was refractory to both lenalidomide and thalidomide.

The patient’s treatment-free interval prior to PAT-SM6 was 12 months. After PAT-SM6, the patient was therapy-free for 5.2 months.

The researchers said additional trials testing PAT-SM6 in combination with other MM therapies are planned. PAT-SM6 has received orphan drug designation for MM in the US and the European Union.

The monoclonal IgM antibody PAT-SM6 was “well-tolerated” and showed “modest clinical activity” in patients with relapsed or refractory multiple myeloma (MM), researchers reported in haematologica.

Adverse events occurred in all 12 patients enrolled in the phase 1/2a study, but most were considered unrelated to treatment.

A third of patients, all of whom had progressive disease upon study entry, achieved stable disease after receiving PAT-SM6. The remaining patients progressed.

Leo Rasche, MD, of University Hospital Wurzburg in Germany, and his colleagues conducted this study. It was funded, in part, by Patrys Limited, the company developing PAT-SM6.

The study included 12 heavily pretreated MM patients. They had a median age of 69.5 years and a long-standing history of MM (range, 3.25 to 15.75 years). They had received a median of 3.9 prior lines of therapy (range, 2-7).

Patients received 4 escalating doses of PAT-SM6, over a period of 2 weeks, via intravenous infusions at 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 6 mg/kg.

Safety data

There were 54 treatment-emergent adverse events in all 12 patients. However, there were no dose-limiting toxicities and no deaths. The maximum tolerated dose has not been reached.

More than 80% of the adverse events were of mild to moderate intensity. Two patients (16.6%) each experienced a single serious event. One patient had acute back pain, and one had a bile duct stone. Neither of these events was considered treatment-related.

Twenty-one adverse events were considered treatment-related. This included leukopenia (66.6%), neutropenia (50%), hypertension (16.6%), catheter-related thrombophlebitis (8.3%), injection site erythema (8.3%), slight headache (8.3%), C-reactive protein increase (8.3%), and hypertriglyceridemia (8.3%).

Efficacy data

Most patients progressed following treatment, but 4 (33.3%) had stable disease. The investigators noted that stable disease is not necessarily connected with a clinical benefit, so they analyzed the 4 patients in detail.

Patient 4, who received PAT-SM6 at 1 mg/kg, entered the study with high-risk disease. The patient had 13q deletion and 1q21 gain, had received 5 prior lines of therapy, and was refractory to novel agents, including pomalidomide and bortezomib.

The patient was treatment-free for 1 month prior to receiving PAT-SM6. During treatment, there were no symptoms of active myeloma, and the patient asked to continue salvage therapy 1 week after the end of the study.

Patient 7, who received PAT-SM6 at 3 mg/kg, had been diagnosed with MM for 15 years and had received 4 prior lines of therapy.

The patient’s treatment-free interval before receiving PAT-SM6 was 30 months. After PAT-SM6, the patient was therapy-free for 4.6 months.

Patient 10, who received PAT-SM6 at 6mg/kg, had 6 prior lines of therapy, including tandem autologous stem cell transplant and several polychemotherapeutic regimens.

The patient was therapy-free for 4 months prior to receiving PAT-SM6. The patient requested salvage therapy 1 month after receiving PAT-SM6.

Patient 11, who received PAT-SM6 at 6mg/kg, had 4 prior lines of therapy and was refractory to both lenalidomide and thalidomide.

The patient’s treatment-free interval prior to PAT-SM6 was 12 months. After PAT-SM6, the patient was therapy-free for 5.2 months.

The researchers said additional trials testing PAT-SM6 in combination with other MM therapies are planned. PAT-SM6 has received orphan drug designation for MM in the US and the European Union.

The monoclonal IgM antibody PAT-SM6 was “well-tolerated” and showed “modest clinical activity” in patients with relapsed or refractory multiple myeloma (MM), researchers reported in haematologica.

Adverse events occurred in all 12 patients enrolled in the phase 1/2a study, but most were considered unrelated to treatment.

A third of patients, all of whom had progressive disease upon study entry, achieved stable disease after receiving PAT-SM6. The remaining patients progressed.

Leo Rasche, MD, of University Hospital Wurzburg in Germany, and his colleagues conducted this study. It was funded, in part, by Patrys Limited, the company developing PAT-SM6.

The study included 12 heavily pretreated MM patients. They had a median age of 69.5 years and a long-standing history of MM (range, 3.25 to 15.75 years). They had received a median of 3.9 prior lines of therapy (range, 2-7).

Patients received 4 escalating doses of PAT-SM6, over a period of 2 weeks, via intravenous infusions at 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 6 mg/kg.

Safety data

There were 54 treatment-emergent adverse events in all 12 patients. However, there were no dose-limiting toxicities and no deaths. The maximum tolerated dose has not been reached.

More than 80% of the adverse events were of mild to moderate intensity. Two patients (16.6%) each experienced a single serious event. One patient had acute back pain, and one had a bile duct stone. Neither of these events was considered treatment-related.

Twenty-one adverse events were considered treatment-related. This included leukopenia (66.6%), neutropenia (50%), hypertension (16.6%), catheter-related thrombophlebitis (8.3%), injection site erythema (8.3%), slight headache (8.3%), C-reactive protein increase (8.3%), and hypertriglyceridemia (8.3%).

Efficacy data

Most patients progressed following treatment, but 4 (33.3%) had stable disease. The investigators noted that stable disease is not necessarily connected with a clinical benefit, so they analyzed the 4 patients in detail.

Patient 4, who received PAT-SM6 at 1 mg/kg, entered the study with high-risk disease. The patient had 13q deletion and 1q21 gain, had received 5 prior lines of therapy, and was refractory to novel agents, including pomalidomide and bortezomib.

The patient was treatment-free for 1 month prior to receiving PAT-SM6. During treatment, there were no symptoms of active myeloma, and the patient asked to continue salvage therapy 1 week after the end of the study.

Patient 7, who received PAT-SM6 at 3 mg/kg, had been diagnosed with MM for 15 years and had received 4 prior lines of therapy.

The patient’s treatment-free interval before receiving PAT-SM6 was 30 months. After PAT-SM6, the patient was therapy-free for 4.6 months.

Patient 10, who received PAT-SM6 at 6mg/kg, had 6 prior lines of therapy, including tandem autologous stem cell transplant and several polychemotherapeutic regimens.

The patient was therapy-free for 4 months prior to receiving PAT-SM6. The patient requested salvage therapy 1 month after receiving PAT-SM6.

Patient 11, who received PAT-SM6 at 6mg/kg, had 4 prior lines of therapy and was refractory to both lenalidomide and thalidomide.

The patient’s treatment-free interval prior to PAT-SM6 was 12 months. After PAT-SM6, the patient was therapy-free for 5.2 months.

The researchers said additional trials testing PAT-SM6 in combination with other MM therapies are planned. PAT-SM6 has received orphan drug designation for MM in the US and the European Union.

New research suggests vitamin A may reduce the risk of malaria in young children.

The study showed that children under 5 living in sub-Saharan Africa were 54% less likely to develop malaria if they had been given a single, large dose of vitamin A.

The finding, published in eLife, indicates that vitamin A may be able to protect children from the malaria parasite, especially if administered during the wet season, when malaria-infected mosquitos are most prevalent.

“Now, we need to test vitamin A in a randomized, controlled, clinical trial to better understand whether this could really be an effective way to prevent this disease,” said study author Maria-Graciela Hollm-Delgado, PhD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland.

Dr Hollm-Delgado and her colleagues analyzed national survey data from 4 sub-Saharan countries—Burkina Faso, Mozambique, Rwanda, and Senegal—on children between the ages of 6 months and 59 months.

The goal was to determine the risk of Plasmodium parasitemia (n=8390) and Plasmodium falciparum-specific antigenemia (n=6121) following vitamin A supplementation and vaccinations.

The researchers found the measles and polio vaccines were not associated with malaria. And Bacille Calmette Guerin vaccination was associated with an increased risk of antigenemia (relative risk [RR]=4.06) but not parasitemia.

Only vitamin A was protective against malaria. Children who received vitamin A were less likely to present with parasitemia (RR=0.46) and antigenemia (RR=0.23).

Vitamin A appeared to be more protective under certain circumstances, including when administered during the rainy season, as well as when given to older children and when more time had passed since supplementation.

The researchers aren’t certain why vitamin A would reduce the rate of malaria infection, but they suspect it is because vitamin A, which is known to boost immunity and improve the ability to fight off infection, may help the body clear out the malaria parasite more quickly.

Only 62% of children in the study had received vitamin A supplementation, even though World Health Organization guidelines recommend that all children in sub-Saharan Africa receive a single, large dose of vitamin A.

Rates were higher for many vaccinations, Dr Hollm-Delgado said, noting that the guidelines for vitamin A aren’t as specific as they are for most vaccinations.

New research suggests vitamin A may reduce the risk of malaria in young children.

The study showed that children under 5 living in sub-Saharan Africa were 54% less likely to develop malaria if they had been given a single, large dose of vitamin A.

The finding, published in eLife, indicates that vitamin A may be able to protect children from the malaria parasite, especially if administered during the wet season, when malaria-infected mosquitos are most prevalent.

“Now, we need to test vitamin A in a randomized, controlled, clinical trial to better understand whether this could really be an effective way to prevent this disease,” said study author Maria-Graciela Hollm-Delgado, PhD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland.

Dr Hollm-Delgado and her colleagues analyzed national survey data from 4 sub-Saharan countries—Burkina Faso, Mozambique, Rwanda, and Senegal—on children between the ages of 6 months and 59 months.

The goal was to determine the risk of Plasmodium parasitemia (n=8390) and Plasmodium falciparum-specific antigenemia (n=6121) following vitamin A supplementation and vaccinations.

The researchers found the measles and polio vaccines were not associated with malaria. And Bacille Calmette Guerin vaccination was associated with an increased risk of antigenemia (relative risk [RR]=4.06) but not parasitemia.

Only vitamin A was protective against malaria. Children who received vitamin A were less likely to present with parasitemia (RR=0.46) and antigenemia (RR=0.23).

Vitamin A appeared to be more protective under certain circumstances, including when administered during the rainy season, as well as when given to older children and when more time had passed since supplementation.

The researchers aren’t certain why vitamin A would reduce the rate of malaria infection, but they suspect it is because vitamin A, which is known to boost immunity and improve the ability to fight off infection, may help the body clear out the malaria parasite more quickly.

Only 62% of children in the study had received vitamin A supplementation, even though World Health Organization guidelines recommend that all children in sub-Saharan Africa receive a single, large dose of vitamin A.

Rates were higher for many vaccinations, Dr Hollm-Delgado said, noting that the guidelines for vitamin A aren’t as specific as they are for most vaccinations.

New research suggests vitamin A may reduce the risk of malaria in young children.

The study showed that children under 5 living in sub-Saharan Africa were 54% less likely to develop malaria if they had been given a single, large dose of vitamin A.

The finding, published in eLife, indicates that vitamin A may be able to protect children from the malaria parasite, especially if administered during the wet season, when malaria-infected mosquitos are most prevalent.

“Now, we need to test vitamin A in a randomized, controlled, clinical trial to better understand whether this could really be an effective way to prevent this disease,” said study author Maria-Graciela Hollm-Delgado, PhD, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland.

Dr Hollm-Delgado and her colleagues analyzed national survey data from 4 sub-Saharan countries—Burkina Faso, Mozambique, Rwanda, and Senegal—on children between the ages of 6 months and 59 months.

The goal was to determine the risk of Plasmodium parasitemia (n=8390) and Plasmodium falciparum-specific antigenemia (n=6121) following vitamin A supplementation and vaccinations.

The researchers found the measles and polio vaccines were not associated with malaria. And Bacille Calmette Guerin vaccination was associated with an increased risk of antigenemia (relative risk [RR]=4.06) but not parasitemia.

Only vitamin A was protective against malaria. Children who received vitamin A were less likely to present with parasitemia (RR=0.46) and antigenemia (RR=0.23).

Vitamin A appeared to be more protective under certain circumstances, including when administered during the rainy season, as well as when given to older children and when more time had passed since supplementation.

The researchers aren’t certain why vitamin A would reduce the rate of malaria infection, but they suspect it is because vitamin A, which is known to boost immunity and improve the ability to fight off infection, may help the body clear out the malaria parasite more quickly.

Only 62% of children in the study had received vitamin A supplementation, even though World Health Organization guidelines recommend that all children in sub-Saharan Africa receive a single, large dose of vitamin A.

Rates were higher for many vaccinations, Dr Hollm-Delgado said, noting that the guidelines for vitamin A aren’t as specific as they are for most vaccinations.

A 79-year-old man presents for a routine skin check, in the context of his 40-year history of nonmelanoma skin cancer. He grew up on a farm and then became a farmer himself, spending almost every day in the sun (usually without a hat). His skin burned easily but would take on a “tan” by the start of summer.

In the succeeding years, he developed so many skin cancers (and had them removed) that he lost count. All were basal cell or squamous cell carcinomas, predominately manifesting on his face, arms, and ears. Several required Mohs surgery for removal.

EXAMINATION
Abundant evidence of excessive sun exposure is seen on the patient’s skin: actinic keratoses on the forehead, ears, and neck, and multiple solar lentigines on the face, neck, and arms. On his left neck, below the ear, is a large, oddly pigmented, dark macular patch. Dermatoscopic examination reveals focal pigmentary clumping and streaming, which prompts the decision to perform an incisional biopsy. The darkest and most irregular part of the lesion is taken as a sample. The pathology report shows lentigo maligna.

What is lentigo maligna?

 

DISCUSSION
Lentigo maligna (LM), also known as Hutchinson freckle, is a type of melanoma in situ that is typically seen on sun-exposed skin. It has indistinct margins with predominantly brown and black coloration. LM is usually seen on older, mostly fair-skinned patients who have a history of extensive sun exposure. Its preferred sites include the face, ears, neck, and upper extremities.

LM is, by definition, entirely superficial and therefore safe. Its main significance is that it can become focally invasive to the dermis, a phenomenon termed lentigo maligna melanoma (LMM). When that occurs, the clusters of spindle-shaped atypical cells can then progress to a vertical growth phase, resulting in intravascular invasion that eventuates in metastasis.

LMs grow so slowly that they often escape detection; they are sometimes mistaken for solar lentigines (SL). They can “collide” with SLs or other benign lesions (eg, seborrheic keratoses), which can effectively camouflage them. Suspicion is usually triggered by change (color, size) in a lesion.

Biopsy is the only method of detection. In this case, the central portion of this large, oddly pigmented and bordered, multicolored patch was excised and the darkest, most irregular part of the lesion collected. This is the gold standard for biopsy of a potential melanoma. A large deep shave biopsy (“saucerization”) would have accomplished the same thing; studies show that neither process will cause metastasis. The main mistake to avoid is performing a single punch biopsy, which risks a false-negative result.

The definitive surgical approach is to remove the lesion with a 1-cm margin around it and into the underlying adipose layer. The wound can either be left to heal by secondary intention or closed primarily. Either way, this patient’s prognosis is excellent, unless the final pathology report indicates focal invasion. With a patient of this age, the LM could have been left alone—although, once discovered, LM is irresistibly compelling to treat.

TAKE-HOME LEARNING POINTS
• Lentigo maligna (LM) is a type of melanoma in situ with the potential to progress to lentigo maligna melanoma, an invasive form of early melanoma.

• LM is common on sun-exposed skin of older patients with a history of excessive sun exposure.

• Faces, ears, arms, and necks are common areas for LM to manifest.

• Biopsy of suspected melanoma should incorporate a significant portion of the darkest, most irregular part of the lesion; it can be done by incisional technique or deep saucerization.

• LM is also known as Hutchinson freckle, since it often resembles a large, irregularly bordered and pigmented freckle.

A 79-year-old man presents for a routine skin check, in the context of his 40-year history of nonmelanoma skin cancer. He grew up on a farm and then became a farmer himself, spending almost every day in the sun (usually without a hat). His skin burned easily but would take on a “tan” by the start of summer.

In the succeeding years, he developed so many skin cancers (and had them removed) that he lost count. All were basal cell or squamous cell carcinomas, predominately manifesting on his face, arms, and ears. Several required Mohs surgery for removal.

EXAMINATION
Abundant evidence of excessive sun exposure is seen on the patient’s skin: actinic keratoses on the forehead, ears, and neck, and multiple solar lentigines on the face, neck, and arms. On his left neck, below the ear, is a large, oddly pigmented, dark macular patch. Dermatoscopic examination reveals focal pigmentary clumping and streaming, which prompts the decision to perform an incisional biopsy. The darkest and most irregular part of the lesion is taken as a sample. The pathology report shows lentigo maligna.

What is lentigo maligna?

 

DISCUSSION
Lentigo maligna (LM), also known as Hutchinson freckle, is a type of melanoma in situ that is typically seen on sun-exposed skin. It has indistinct margins with predominantly brown and black coloration. LM is usually seen on older, mostly fair-skinned patients who have a history of extensive sun exposure. Its preferred sites include the face, ears, neck, and upper extremities.

LM is, by definition, entirely superficial and therefore safe. Its main significance is that it can become focally invasive to the dermis, a phenomenon termed lentigo maligna melanoma (LMM). When that occurs, the clusters of spindle-shaped atypical cells can then progress to a vertical growth phase, resulting in intravascular invasion that eventuates in metastasis.

LMs grow so slowly that they often escape detection; they are sometimes mistaken for solar lentigines (SL). They can “collide” with SLs or other benign lesions (eg, seborrheic keratoses), which can effectively camouflage them. Suspicion is usually triggered by change (color, size) in a lesion.

Biopsy is the only method of detection. In this case, the central portion of this large, oddly pigmented and bordered, multicolored patch was excised and the darkest, most irregular part of the lesion collected. This is the gold standard for biopsy of a potential melanoma. A large deep shave biopsy (“saucerization”) would have accomplished the same thing; studies show that neither process will cause metastasis. The main mistake to avoid is performing a single punch biopsy, which risks a false-negative result.

The definitive surgical approach is to remove the lesion with a 1-cm margin around it and into the underlying adipose layer. The wound can either be left to heal by secondary intention or closed primarily. Either way, this patient’s prognosis is excellent, unless the final pathology report indicates focal invasion. With a patient of this age, the LM could have been left alone—although, once discovered, LM is irresistibly compelling to treat.

TAKE-HOME LEARNING POINTS
• Lentigo maligna (LM) is a type of melanoma in situ with the potential to progress to lentigo maligna melanoma, an invasive form of early melanoma.

• LM is common on sun-exposed skin of older patients with a history of excessive sun exposure.

• Faces, ears, arms, and necks are common areas for LM to manifest.

• Biopsy of suspected melanoma should incorporate a significant portion of the darkest, most irregular part of the lesion; it can be done by incisional technique or deep saucerization.

• LM is also known as Hutchinson freckle, since it often resembles a large, irregularly bordered and pigmented freckle.

A 79-year-old man presents for a routine skin check, in the context of his 40-year history of nonmelanoma skin cancer. He grew up on a farm and then became a farmer himself, spending almost every day in the sun (usually without a hat). His skin burned easily but would take on a “tan” by the start of summer.

In the succeeding years, he developed so many skin cancers (and had them removed) that he lost count. All were basal cell or squamous cell carcinomas, predominately manifesting on his face, arms, and ears. Several required Mohs surgery for removal.

EXAMINATION
Abundant evidence of excessive sun exposure is seen on the patient’s skin: actinic keratoses on the forehead, ears, and neck, and multiple solar lentigines on the face, neck, and arms. On his left neck, below the ear, is a large, oddly pigmented, dark macular patch. Dermatoscopic examination reveals focal pigmentary clumping and streaming, which prompts the decision to perform an incisional biopsy. The darkest and most irregular part of the lesion is taken as a sample. The pathology report shows lentigo maligna.

What is lentigo maligna?

 

DISCUSSION
Lentigo maligna (LM), also known as Hutchinson freckle, is a type of melanoma in situ that is typically seen on sun-exposed skin. It has indistinct margins with predominantly brown and black coloration. LM is usually seen on older, mostly fair-skinned patients who have a history of extensive sun exposure. Its preferred sites include the face, ears, neck, and upper extremities.

LM is, by definition, entirely superficial and therefore safe. Its main significance is that it can become focally invasive to the dermis, a phenomenon termed lentigo maligna melanoma (LMM). When that occurs, the clusters of spindle-shaped atypical cells can then progress to a vertical growth phase, resulting in intravascular invasion that eventuates in metastasis.

LMs grow so slowly that they often escape detection; they are sometimes mistaken for solar lentigines (SL). They can “collide” with SLs or other benign lesions (eg, seborrheic keratoses), which can effectively camouflage them. Suspicion is usually triggered by change (color, size) in a lesion.

Biopsy is the only method of detection. In this case, the central portion of this large, oddly pigmented and bordered, multicolored patch was excised and the darkest, most irregular part of the lesion collected. This is the gold standard for biopsy of a potential melanoma. A large deep shave biopsy (“saucerization”) would have accomplished the same thing; studies show that neither process will cause metastasis. The main mistake to avoid is performing a single punch biopsy, which risks a false-negative result.

The definitive surgical approach is to remove the lesion with a 1-cm margin around it and into the underlying adipose layer. The wound can either be left to heal by secondary intention or closed primarily. Either way, this patient’s prognosis is excellent, unless the final pathology report indicates focal invasion. With a patient of this age, the LM could have been left alone—although, once discovered, LM is irresistibly compelling to treat.

TAKE-HOME LEARNING POINTS
• Lentigo maligna (LM) is a type of melanoma in situ with the potential to progress to lentigo maligna melanoma, an invasive form of early melanoma.

• LM is common on sun-exposed skin of older patients with a history of excessive sun exposure.

• Faces, ears, arms, and necks are common areas for LM to manifest.

• Biopsy of suspected melanoma should incorporate a significant portion of the darkest, most irregular part of the lesion; it can be done by incisional technique or deep saucerization.

• LM is also known as Hutchinson freckle, since it often resembles a large, irregularly bordered and pigmented freckle.

DTI Reveals Changes in Brain Connections in Early Alzheimer’s Disease
Changes in brain connections visible on MRI could represent an imaging biomarker of Alzheimer’s disease, according to a study presented at the meeting.

As many as five million Americans have Alzheimer’s disease, and this number is expected to increase to 14 million by 2050, according to the Centers for Disease Control and Prevention. Preventive treatments may be most effective before Alzheimer’s disease is diagnosed, such as when a person is experiencing mild cognitive impairment.

Previous efforts at early detection have focused on beta amyloid. For the current study, researchers looked at the brain’s structural connectome, a map of white matter tracts that carry signals between various areas of the brain.

“The structural connectome provides us with a way to characterize and measure these connections and how they change through disease or age,” said Jeffrey W. Prescott, MD, PhD, a radiology resident at Duke University Medical Center in Durham, North Carolina, and a coauthor of the study.

Dr. Prescott and colleagues analyzed data for 102 patients enrolled in a national study called the Alzheimer’s Disease Neuroimaging Initiative 2. The patients had undergone diffusion tensor imaging (DTI), which assesses the integrity of white matter tracts in the brain by measuring how easy it is for water to move along them. “Water prefers moving along the defined physical connections between regions in the brain, which makes DTI a great tool for evaluating the structural connectome,” said Dr. Prescott.

The researchers compared changes in the structural connectome with results from florbetapir PET imaging, a technique that measures the amount of beta amyloid plaque in the brain. The results showed a strong association between florbetapir uptake and decreases in the strength of the structural connectome in each of the five areas of the brain studied.

“This study ties together two of the major changes in the Alzheimer’s brain—structural tissue changes and pathologic amyloid plaque deposition—and suggests a promising role for DTI as a possible diagnostic adjunct,” said Dr. Prescott.

Based on these findings, DTI may have a role in assessing brain damage in early Alzheimer’s disease and in monitoring the effect of new therapies.

“Traditionally, Alzheimer’s disease is believed to exert its effects on thinking via damage to the brain’s gray matter, where most of the nerve cells are concentrated,” said Jeffrey R. Petrella, MD, Professor of Radiology at Duke University and senior author of the research. “This study suggests that amyloid deposition in the gray matter affects the associated white matter connections, which are essential for conducting messages across the billions of nerve cells in the brain, allowing for all aspects of mental function.”

“We suspect that as amyloid plaque load in the gray matter increases, the brain’s white matter starts to break down or malfunction and lose its ability to move water and neurochemicals efficiently,” added Dr. Prescott.

The researchers plan to continue studying this cohort of patients over time to gain a better understanding of how the disease evolves in individual patients. They also intend to incorporate functional imaging into their research to learn about how the relationship between function and structure changes with increasing amyloid burden.

Asymptomatic Atherosclerosis May Be Associated With Cognitive Impairment
A buildup of plaque in the body’s major arteries is associated with mild cognitive impairment, according to a study of approximately 2,000 adults conducted at the University of Texas (UT) Southwestern Medical Center.

“It is well established that plaque buildup in the arteries is a predictor of heart disease, but the relationship between atherosclerosis and brain health is less clear,” said Christopher D. Maroules, MD, a radiology resident at UT Southwestern Medical Center in Dallas. “Our findings suggest that atherosclerosis not only affects the heart, but also brain health.”

Researchers analyzed the test results of 1,903 participants (mean age, 44) in the Dallas Heart Study, a multiethnic population-based study of adults from Dallas County, Texas. The participants included men and women who had no symptoms of cardiovascular disease.

Study participants completed the Montreal Cognitive Assessment (MoCA), a 30-point standardized test for detecting mild cognitive impairment, and underwent MRI of the brain to measure white matter hyperintensity volume. Bright white spots known as high signal intensity areas on a brain MRI indicate abnormal changes within the white matter.

“Increased white matter hyperintensity volume is part of the normal aging process,” explained Dr. Maroules. “But excessive white matter hyperintensity volume is a marker for cognitive impairment.”

Study participants also underwent imaging exams to measure the buildup of plaque in the arteries in three distinct vascular areas of the body. They underwent MRI to measure wall thickness in the carotid arteries and in the abdominal aorta, and received CT to measure coronary artery calcium.

 

Using the results, researchers performed a statistical regression to understand the relationship between the incidence of atherosclerosis and mild cognitive impairment. After adjusting for traditional risk factors for atherosclerosis, including age, ethnicity, male sex, diabetes, hypertension, smoking, and BMI, the investigators found independent relationships between atherosclerosis in all three vascular areas of the body and cognitive health, as measured by MoCA scores, and white matter hyperintensity volume on MRI.

Individuals in the highest quartile of internal carotid wall thickness were 21% more likely to have cognitive impairment, as indicated by a low MoCA score. An increasing coronary artery calcium score was predictive of large white matter intensity volume on MRI.

“These results underscore the importance of identifying atherosclerosis in its early stages, not just to help preserve heart function, but also to preserve cognition and brain health,” said Dr. Maroules. The MRI and CT imaging techniques provide valuable prognostic information about an individual’s downstream health risks, he added.

“Plaque buildup in blood vessels throughout the body offers us a window into brain health. Imaging with CT and MRI has an important role in identifying patients who are at a higher risk for cognitive impairment.”

A Season of High School Football Without Concussion May Cause Brain Changes
Some high school football players exhibit measurable brain changes after a single season of play, even in the absence of concussion, according to a study presented at the meeting.

“This study adds to the growing body of evidence that a season of play in a contact sport can affect the brain in the absence of clinical findings,” said Christopher T. Whitlow, MD, PhD, MHA, Associate Professor of Radiology at Wake Forest School of Medicine and radiologist at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.

In recent years, various reports have suggested the potential effects that participation in youth sports may have on the developing brain. Most of these studies have looked at brain changes as a result of concussion, however. Dr. Whitlow and colleagues set out to determine whether head impacts withstood in the course of a season of high school football produce white matter changes in the brain in the absence of clinically diagnosed concussion.

The researchers studied 24 high school football players between the ages of 16 and 18. For all games and practices, players were monitored with Head Impact Telemetry System (HITs) helmet-mounted accelerometers, which are used in youth and collegiate football to assess the frequency and severity of helmet impacts.

Risk-weighted cumulative exposure was computed from the HITs data and represented the risk of concussion over the course of the season. These data, along with the total number of impacts, were used to categorize the players as heavy hitters or light hitters. The researchers identified nine of the 24 participants as heavy hitters and 15 as light hitters. None of the players had concussion during the season.

All players underwent pre- and post-season evaluation with diffusion tensor imaging (DTI) of the brain. Diffusion tensor imaging measures fractional anisotropy, which indicates the movement of water molecules along axons. In healthy white matter, the direction of water movement is fairly uniform, and fractional anisotropy is high. When water movement is more random, fractional anisotropy values decrease, thus suggesting microstructural abnormalities.

The results showed that both groups demonstrated global increases of fractional anisotropy over time, likely reflecting the effects of brain development. However, the heavy-hitter group showed statistically significant areas of decreased fractional anisotropy post-season in specific areas of the brain, including the splenium of the corpus callosum and deep white matter tracts.

“Our study found that players experiencing greater levels of head impacts have more fractional anisotropy loss, compared with players with lower impact exposure,” said Dr. Whitlow. “Similar brain MRI changes have been previously associated with mild traumatic brain injury. However, it is unclear whether or not these effects will be associated with any negative long-term consequences.” These findings are preliminary, and more study needs to be performed, concluded Dr. Whitlow.

Mild Coronary Artery Disease Increases Risk of Cardiovascular Events
Patients with diabetes and mild coronary artery disease have the same relative risk for a heart attack or other major adverse heart event as patients with diabetes and serious single-vessel obstructive disease, according to a long-term study.

Researchers at the University of British Columbia and St. Paul’s Hospital in Vancouver analyzed data from the Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter (CONFIRM) Registry, which was developed to examine the prognostic value of cardiac computed tomography angiography (CCTA) for predicting adverse cardiac events related to coronary artery disease. The registry, which has CCTA data for 40,000 patients from 17 centers around the world, now has five-year follow-up data for 14,000 patients.

 

“The CONFIRM Registry is the largest long-term data set available and allowed us to evaluate the long-term prognostic value of CCTA in diabetic patients,” said Jonathan Leipsic, MD, vice chairman of the Department of Radiology at the University of British Columbia and study coauthor.

The researchers analyzed data for 1,823 patients with diabetes who underwent CCTA to detect and determine the extent of coronary artery disease. Men and women (median age, 61.7) in the study were categorized as having no coronary artery disease, mild disease (ie, coronary artery narrowed by less than 50%), or obstructive disease (ie, obstruction of more than 50% of the artery). Over a 5.2-year follow-up period, 246 deaths occurred, representing 13.5% of the total study group.

Major adverse cardiovascular event (MACE) data were available for 973 patients. During the follow-up period, 295 (30.3%) of the patients had a MACE, such as heart attack or a coronary revascularization.

The researchers found that both obstructive and mild, or nonobstructive, coronary artery disease, as determined by CCTA, were associated with patient deaths and MACE. Most importantly, the researchers found that the relative risk for death or MACE for a patient with mild coronary artery disease was comparable to that of patients with single vessel obstructive disease.

“Until now, two-year follow-up studies suggested that a diabetic patient with mild or nonobstructive coronary artery disease had a lower risk of major adverse cardiovascular events and death than patients with obstructive disease,” said Philipp Blanke, MD, a radiologist at the University of British Columbia and St. Paul’s Hospital and a coauthor of the study. “Our five-year follow-up data suggest that nonobstructive and obstructive coronary artery disease, as detected by cardiac CTA in diabetic patients, are both associated with higher rates of mortality.”

Researchers need a better understanding of the evolution of plaque in the arteries and of patient response to therapies, said Dr. Leipsic. “Cardiac CT angiography is helpful for identifying diabetic patients who are at higher risk for heart events and who may benefit from more aggressive therapy to help modify that risk,” he added.

Patients Prefer Direct Access to Imaging Records
Patients value direct, independent access to their medical exams, researchers reported.

Giampaolo Greco, PhD, MPH, Assistant Professor in the Department of Population Health Science and Policy at the Mount Sinai School of Medicine in New York City, and colleagues set out to evaluate patient and provider satisfaction with RSNA Image Share, an Internet-based interoperable image exchange system that gives patients ownership of their imaging exams and control over access to their imaging records. The network enables radiology sites to make results of imaging exams available for patients to incorporate in personal health record (PHR) accounts they can use to securely store, manage, and share their imaging records. Sites also can use the network to send patient imaging records to other participating sites to support better informed care.

For the study, patients undergoing radiologic exams at four academic centers were eligible to establish online PHR accounts using the RSNA Image Share network. Patients could then use their PHR accounts to maintain and share their images with selected providers, creating a detailed medical history accessible through any secure Internet connection.

Between July 2012 and August 2013, the study enrolled 2,562 patients, mean age 50.4, including a significant representation of older individuals. Older individuals have the highest healthcare utilization and often experience or perceive a significant barrier in using information technology.

The median number of exams uploaded per patient was six. Study participants were provided a brief survey to assess patient and physician experience with the exchange of images, and 502 patients completed and returned their surveys. Of these respondents, 448 patients identified the method used at the visit to share images: Internet, CDs, both Internet and CDs, or other, and 165 included a section completed by their physician.

Nearly all (96%) of the patients responded positively to having direct access to their medical images, and 78% viewed their images independently. There was no difference between Internet and CD users in satisfaction with privacy and security and timeliness of access to medical images. A greater percentage of Internet users reported being able to access their images without difficulty, compared with CD users (88.3% vs 77.5%).

DTI Reveals Changes in Brain Connections in Early Alzheimer’s Disease
Changes in brain connections visible on MRI could represent an imaging biomarker of Alzheimer’s disease, according to a study presented at the meeting.

As many as five million Americans have Alzheimer’s disease, and this number is expected to increase to 14 million by 2050, according to the Centers for Disease Control and Prevention. Preventive treatments may be most effective before Alzheimer’s disease is diagnosed, such as when a person is experiencing mild cognitive impairment.

Previous efforts at early detection have focused on beta amyloid. For the current study, researchers looked at the brain’s structural connectome, a map of white matter tracts that carry signals between various areas of the brain.

“The structural connectome provides us with a way to characterize and measure these connections and how they change through disease or age,” said Jeffrey W. Prescott, MD, PhD, a radiology resident at Duke University Medical Center in Durham, North Carolina, and a coauthor of the study.

Dr. Prescott and colleagues analyzed data for 102 patients enrolled in a national study called the Alzheimer’s Disease Neuroimaging Initiative 2. The patients had undergone diffusion tensor imaging (DTI), which assesses the integrity of white matter tracts in the brain by measuring how easy it is for water to move along them. “Water prefers moving along the defined physical connections between regions in the brain, which makes DTI a great tool for evaluating the structural connectome,” said Dr. Prescott.

The researchers compared changes in the structural connectome with results from florbetapir PET imaging, a technique that measures the amount of beta amyloid plaque in the brain. The results showed a strong association between florbetapir uptake and decreases in the strength of the structural connectome in each of the five areas of the brain studied.

“This study ties together two of the major changes in the Alzheimer’s brain—structural tissue changes and pathologic amyloid plaque deposition—and suggests a promising role for DTI as a possible diagnostic adjunct,” said Dr. Prescott.

Based on these findings, DTI may have a role in assessing brain damage in early Alzheimer’s disease and in monitoring the effect of new therapies.

“Traditionally, Alzheimer’s disease is believed to exert its effects on thinking via damage to the brain’s gray matter, where most of the nerve cells are concentrated,” said Jeffrey R. Petrella, MD, Professor of Radiology at Duke University and senior author of the research. “This study suggests that amyloid deposition in the gray matter affects the associated white matter connections, which are essential for conducting messages across the billions of nerve cells in the brain, allowing for all aspects of mental function.”

“We suspect that as amyloid plaque load in the gray matter increases, the brain’s white matter starts to break down or malfunction and lose its ability to move water and neurochemicals efficiently,” added Dr. Prescott.

The researchers plan to continue studying this cohort of patients over time to gain a better understanding of how the disease evolves in individual patients. They also intend to incorporate functional imaging into their research to learn about how the relationship between function and structure changes with increasing amyloid burden.

Asymptomatic Atherosclerosis May Be Associated With Cognitive Impairment
A buildup of plaque in the body’s major arteries is associated with mild cognitive impairment, according to a study of approximately 2,000 adults conducted at the University of Texas (UT) Southwestern Medical Center.

“It is well established that plaque buildup in the arteries is a predictor of heart disease, but the relationship between atherosclerosis and brain health is less clear,” said Christopher D. Maroules, MD, a radiology resident at UT Southwestern Medical Center in Dallas. “Our findings suggest that atherosclerosis not only affects the heart, but also brain health.”

Researchers analyzed the test results of 1,903 participants (mean age, 44) in the Dallas Heart Study, a multiethnic population-based study of adults from Dallas County, Texas. The participants included men and women who had no symptoms of cardiovascular disease.

Study participants completed the Montreal Cognitive Assessment (MoCA), a 30-point standardized test for detecting mild cognitive impairment, and underwent MRI of the brain to measure white matter hyperintensity volume. Bright white spots known as high signal intensity areas on a brain MRI indicate abnormal changes within the white matter.

“Increased white matter hyperintensity volume is part of the normal aging process,” explained Dr. Maroules. “But excessive white matter hyperintensity volume is a marker for cognitive impairment.”

Study participants also underwent imaging exams to measure the buildup of plaque in the arteries in three distinct vascular areas of the body. They underwent MRI to measure wall thickness in the carotid arteries and in the abdominal aorta, and received CT to measure coronary artery calcium.

 

Using the results, researchers performed a statistical regression to understand the relationship between the incidence of atherosclerosis and mild cognitive impairment. After adjusting for traditional risk factors for atherosclerosis, including age, ethnicity, male sex, diabetes, hypertension, smoking, and BMI, the investigators found independent relationships between atherosclerosis in all three vascular areas of the body and cognitive health, as measured by MoCA scores, and white matter hyperintensity volume on MRI.

Individuals in the highest quartile of internal carotid wall thickness were 21% more likely to have cognitive impairment, as indicated by a low MoCA score. An increasing coronary artery calcium score was predictive of large white matter intensity volume on MRI.

“These results underscore the importance of identifying atherosclerosis in its early stages, not just to help preserve heart function, but also to preserve cognition and brain health,” said Dr. Maroules. The MRI and CT imaging techniques provide valuable prognostic information about an individual’s downstream health risks, he added.

“Plaque buildup in blood vessels throughout the body offers us a window into brain health. Imaging with CT and MRI has an important role in identifying patients who are at a higher risk for cognitive impairment.”

A Season of High School Football Without Concussion May Cause Brain Changes
Some high school football players exhibit measurable brain changes after a single season of play, even in the absence of concussion, according to a study presented at the meeting.

“This study adds to the growing body of evidence that a season of play in a contact sport can affect the brain in the absence of clinical findings,” said Christopher T. Whitlow, MD, PhD, MHA, Associate Professor of Radiology at Wake Forest School of Medicine and radiologist at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.

In recent years, various reports have suggested the potential effects that participation in youth sports may have on the developing brain. Most of these studies have looked at brain changes as a result of concussion, however. Dr. Whitlow and colleagues set out to determine whether head impacts withstood in the course of a season of high school football produce white matter changes in the brain in the absence of clinically diagnosed concussion.

The researchers studied 24 high school football players between the ages of 16 and 18. For all games and practices, players were monitored with Head Impact Telemetry System (HITs) helmet-mounted accelerometers, which are used in youth and collegiate football to assess the frequency and severity of helmet impacts.

Risk-weighted cumulative exposure was computed from the HITs data and represented the risk of concussion over the course of the season. These data, along with the total number of impacts, were used to categorize the players as heavy hitters or light hitters. The researchers identified nine of the 24 participants as heavy hitters and 15 as light hitters. None of the players had concussion during the season.

All players underwent pre- and post-season evaluation with diffusion tensor imaging (DTI) of the brain. Diffusion tensor imaging measures fractional anisotropy, which indicates the movement of water molecules along axons. In healthy white matter, the direction of water movement is fairly uniform, and fractional anisotropy is high. When water movement is more random, fractional anisotropy values decrease, thus suggesting microstructural abnormalities.

The results showed that both groups demonstrated global increases of fractional anisotropy over time, likely reflecting the effects of brain development. However, the heavy-hitter group showed statistically significant areas of decreased fractional anisotropy post-season in specific areas of the brain, including the splenium of the corpus callosum and deep white matter tracts.

“Our study found that players experiencing greater levels of head impacts have more fractional anisotropy loss, compared with players with lower impact exposure,” said Dr. Whitlow. “Similar brain MRI changes have been previously associated with mild traumatic brain injury. However, it is unclear whether or not these effects will be associated with any negative long-term consequences.” These findings are preliminary, and more study needs to be performed, concluded Dr. Whitlow.

Mild Coronary Artery Disease Increases Risk of Cardiovascular Events
Patients with diabetes and mild coronary artery disease have the same relative risk for a heart attack or other major adverse heart event as patients with diabetes and serious single-vessel obstructive disease, according to a long-term study.

Researchers at the University of British Columbia and St. Paul’s Hospital in Vancouver analyzed data from the Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter (CONFIRM) Registry, which was developed to examine the prognostic value of cardiac computed tomography angiography (CCTA) for predicting adverse cardiac events related to coronary artery disease. The registry, which has CCTA data for 40,000 patients from 17 centers around the world, now has five-year follow-up data for 14,000 patients.

 

“The CONFIRM Registry is the largest long-term data set available and allowed us to evaluate the long-term prognostic value of CCTA in diabetic patients,” said Jonathan Leipsic, MD, vice chairman of the Department of Radiology at the University of British Columbia and study coauthor.

The researchers analyzed data for 1,823 patients with diabetes who underwent CCTA to detect and determine the extent of coronary artery disease. Men and women (median age, 61.7) in the study were categorized as having no coronary artery disease, mild disease (ie, coronary artery narrowed by less than 50%), or obstructive disease (ie, obstruction of more than 50% of the artery). Over a 5.2-year follow-up period, 246 deaths occurred, representing 13.5% of the total study group.

Major adverse cardiovascular event (MACE) data were available for 973 patients. During the follow-up period, 295 (30.3%) of the patients had a MACE, such as heart attack or a coronary revascularization.

The researchers found that both obstructive and mild, or nonobstructive, coronary artery disease, as determined by CCTA, were associated with patient deaths and MACE. Most importantly, the researchers found that the relative risk for death or MACE for a patient with mild coronary artery disease was comparable to that of patients with single vessel obstructive disease.

“Until now, two-year follow-up studies suggested that a diabetic patient with mild or nonobstructive coronary artery disease had a lower risk of major adverse cardiovascular events and death than patients with obstructive disease,” said Philipp Blanke, MD, a radiologist at the University of British Columbia and St. Paul’s Hospital and a coauthor of the study. “Our five-year follow-up data suggest that nonobstructive and obstructive coronary artery disease, as detected by cardiac CTA in diabetic patients, are both associated with higher rates of mortality.”

Researchers need a better understanding of the evolution of plaque in the arteries and of patient response to therapies, said Dr. Leipsic. “Cardiac CT angiography is helpful for identifying diabetic patients who are at higher risk for heart events and who may benefit from more aggressive therapy to help modify that risk,” he added.

Patients Prefer Direct Access to Imaging Records
Patients value direct, independent access to their medical exams, researchers reported.

Giampaolo Greco, PhD, MPH, Assistant Professor in the Department of Population Health Science and Policy at the Mount Sinai School of Medicine in New York City, and colleagues set out to evaluate patient and provider satisfaction with RSNA Image Share, an Internet-based interoperable image exchange system that gives patients ownership of their imaging exams and control over access to their imaging records. The network enables radiology sites to make results of imaging exams available for patients to incorporate in personal health record (PHR) accounts they can use to securely store, manage, and share their imaging records. Sites also can use the network to send patient imaging records to other participating sites to support better informed care.

For the study, patients undergoing radiologic exams at four academic centers were eligible to establish online PHR accounts using the RSNA Image Share network. Patients could then use their PHR accounts to maintain and share their images with selected providers, creating a detailed medical history accessible through any secure Internet connection.

Between July 2012 and August 2013, the study enrolled 2,562 patients, mean age 50.4, including a significant representation of older individuals. Older individuals have the highest healthcare utilization and often experience or perceive a significant barrier in using information technology.

The median number of exams uploaded per patient was six. Study participants were provided a brief survey to assess patient and physician experience with the exchange of images, and 502 patients completed and returned their surveys. Of these respondents, 448 patients identified the method used at the visit to share images: Internet, CDs, both Internet and CDs, or other, and 165 included a section completed by their physician.

Nearly all (96%) of the patients responded positively to having direct access to their medical images, and 78% viewed their images independently. There was no difference between Internet and CD users in satisfaction with privacy and security and timeliness of access to medical images. A greater percentage of Internet users reported being able to access their images without difficulty, compared with CD users (88.3% vs 77.5%).

DTI Reveals Changes in Brain Connections in Early Alzheimer’s Disease
Changes in brain connections visible on MRI could represent an imaging biomarker of Alzheimer’s disease, according to a study presented at the meeting.

As many as five million Americans have Alzheimer’s disease, and this number is expected to increase to 14 million by 2050, according to the Centers for Disease Control and Prevention. Preventive treatments may be most effective before Alzheimer’s disease is diagnosed, such as when a person is experiencing mild cognitive impairment.

Previous efforts at early detection have focused on beta amyloid. For the current study, researchers looked at the brain’s structural connectome, a map of white matter tracts that carry signals between various areas of the brain.

“The structural connectome provides us with a way to characterize and measure these connections and how they change through disease or age,” said Jeffrey W. Prescott, MD, PhD, a radiology resident at Duke University Medical Center in Durham, North Carolina, and a coauthor of the study.

Dr. Prescott and colleagues analyzed data for 102 patients enrolled in a national study called the Alzheimer’s Disease Neuroimaging Initiative 2. The patients had undergone diffusion tensor imaging (DTI), which assesses the integrity of white matter tracts in the brain by measuring how easy it is for water to move along them. “Water prefers moving along the defined physical connections between regions in the brain, which makes DTI a great tool for evaluating the structural connectome,” said Dr. Prescott.

The researchers compared changes in the structural connectome with results from florbetapir PET imaging, a technique that measures the amount of beta amyloid plaque in the brain. The results showed a strong association between florbetapir uptake and decreases in the strength of the structural connectome in each of the five areas of the brain studied.

“This study ties together two of the major changes in the Alzheimer’s brain—structural tissue changes and pathologic amyloid plaque deposition—and suggests a promising role for DTI as a possible diagnostic adjunct,” said Dr. Prescott.

Based on these findings, DTI may have a role in assessing brain damage in early Alzheimer’s disease and in monitoring the effect of new therapies.

“Traditionally, Alzheimer’s disease is believed to exert its effects on thinking via damage to the brain’s gray matter, where most of the nerve cells are concentrated,” said Jeffrey R. Petrella, MD, Professor of Radiology at Duke University and senior author of the research. “This study suggests that amyloid deposition in the gray matter affects the associated white matter connections, which are essential for conducting messages across the billions of nerve cells in the brain, allowing for all aspects of mental function.”

“We suspect that as amyloid plaque load in the gray matter increases, the brain’s white matter starts to break down or malfunction and lose its ability to move water and neurochemicals efficiently,” added Dr. Prescott.

The researchers plan to continue studying this cohort of patients over time to gain a better understanding of how the disease evolves in individual patients. They also intend to incorporate functional imaging into their research to learn about how the relationship between function and structure changes with increasing amyloid burden.

Asymptomatic Atherosclerosis May Be Associated With Cognitive Impairment
A buildup of plaque in the body’s major arteries is associated with mild cognitive impairment, according to a study of approximately 2,000 adults conducted at the University of Texas (UT) Southwestern Medical Center.

“It is well established that plaque buildup in the arteries is a predictor of heart disease, but the relationship between atherosclerosis and brain health is less clear,” said Christopher D. Maroules, MD, a radiology resident at UT Southwestern Medical Center in Dallas. “Our findings suggest that atherosclerosis not only affects the heart, but also brain health.”

Researchers analyzed the test results of 1,903 participants (mean age, 44) in the Dallas Heart Study, a multiethnic population-based study of adults from Dallas County, Texas. The participants included men and women who had no symptoms of cardiovascular disease.

Study participants completed the Montreal Cognitive Assessment (MoCA), a 30-point standardized test for detecting mild cognitive impairment, and underwent MRI of the brain to measure white matter hyperintensity volume. Bright white spots known as high signal intensity areas on a brain MRI indicate abnormal changes within the white matter.

“Increased white matter hyperintensity volume is part of the normal aging process,” explained Dr. Maroules. “But excessive white matter hyperintensity volume is a marker for cognitive impairment.”

Study participants also underwent imaging exams to measure the buildup of plaque in the arteries in three distinct vascular areas of the body. They underwent MRI to measure wall thickness in the carotid arteries and in the abdominal aorta, and received CT to measure coronary artery calcium.

 

Using the results, researchers performed a statistical regression to understand the relationship between the incidence of atherosclerosis and mild cognitive impairment. After adjusting for traditional risk factors for atherosclerosis, including age, ethnicity, male sex, diabetes, hypertension, smoking, and BMI, the investigators found independent relationships between atherosclerosis in all three vascular areas of the body and cognitive health, as measured by MoCA scores, and white matter hyperintensity volume on MRI.

Individuals in the highest quartile of internal carotid wall thickness were 21% more likely to have cognitive impairment, as indicated by a low MoCA score. An increasing coronary artery calcium score was predictive of large white matter intensity volume on MRI.

“These results underscore the importance of identifying atherosclerosis in its early stages, not just to help preserve heart function, but also to preserve cognition and brain health,” said Dr. Maroules. The MRI and CT imaging techniques provide valuable prognostic information about an individual’s downstream health risks, he added.

“Plaque buildup in blood vessels throughout the body offers us a window into brain health. Imaging with CT and MRI has an important role in identifying patients who are at a higher risk for cognitive impairment.”

A Season of High School Football Without Concussion May Cause Brain Changes
Some high school football players exhibit measurable brain changes after a single season of play, even in the absence of concussion, according to a study presented at the meeting.

“This study adds to the growing body of evidence that a season of play in a contact sport can affect the brain in the absence of clinical findings,” said Christopher T. Whitlow, MD, PhD, MHA, Associate Professor of Radiology at Wake Forest School of Medicine and radiologist at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.

In recent years, various reports have suggested the potential effects that participation in youth sports may have on the developing brain. Most of these studies have looked at brain changes as a result of concussion, however. Dr. Whitlow and colleagues set out to determine whether head impacts withstood in the course of a season of high school football produce white matter changes in the brain in the absence of clinically diagnosed concussion.

The researchers studied 24 high school football players between the ages of 16 and 18. For all games and practices, players were monitored with Head Impact Telemetry System (HITs) helmet-mounted accelerometers, which are used in youth and collegiate football to assess the frequency and severity of helmet impacts.

Risk-weighted cumulative exposure was computed from the HITs data and represented the risk of concussion over the course of the season. These data, along with the total number of impacts, were used to categorize the players as heavy hitters or light hitters. The researchers identified nine of the 24 participants as heavy hitters and 15 as light hitters. None of the players had concussion during the season.

All players underwent pre- and post-season evaluation with diffusion tensor imaging (DTI) of the brain. Diffusion tensor imaging measures fractional anisotropy, which indicates the movement of water molecules along axons. In healthy white matter, the direction of water movement is fairly uniform, and fractional anisotropy is high. When water movement is more random, fractional anisotropy values decrease, thus suggesting microstructural abnormalities.

The results showed that both groups demonstrated global increases of fractional anisotropy over time, likely reflecting the effects of brain development. However, the heavy-hitter group showed statistically significant areas of decreased fractional anisotropy post-season in specific areas of the brain, including the splenium of the corpus callosum and deep white matter tracts.

“Our study found that players experiencing greater levels of head impacts have more fractional anisotropy loss, compared with players with lower impact exposure,” said Dr. Whitlow. “Similar brain MRI changes have been previously associated with mild traumatic brain injury. However, it is unclear whether or not these effects will be associated with any negative long-term consequences.” These findings are preliminary, and more study needs to be performed, concluded Dr. Whitlow.

Mild Coronary Artery Disease Increases Risk of Cardiovascular Events
Patients with diabetes and mild coronary artery disease have the same relative risk for a heart attack or other major adverse heart event as patients with diabetes and serious single-vessel obstructive disease, according to a long-term study.

Researchers at the University of British Columbia and St. Paul’s Hospital in Vancouver analyzed data from the Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter (CONFIRM) Registry, which was developed to examine the prognostic value of cardiac computed tomography angiography (CCTA) for predicting adverse cardiac events related to coronary artery disease. The registry, which has CCTA data for 40,000 patients from 17 centers around the world, now has five-year follow-up data for 14,000 patients.

 

“The CONFIRM Registry is the largest long-term data set available and allowed us to evaluate the long-term prognostic value of CCTA in diabetic patients,” said Jonathan Leipsic, MD, vice chairman of the Department of Radiology at the University of British Columbia and study coauthor.

The researchers analyzed data for 1,823 patients with diabetes who underwent CCTA to detect and determine the extent of coronary artery disease. Men and women (median age, 61.7) in the study were categorized as having no coronary artery disease, mild disease (ie, coronary artery narrowed by less than 50%), or obstructive disease (ie, obstruction of more than 50% of the artery). Over a 5.2-year follow-up period, 246 deaths occurred, representing 13.5% of the total study group.

Major adverse cardiovascular event (MACE) data were available for 973 patients. During the follow-up period, 295 (30.3%) of the patients had a MACE, such as heart attack or a coronary revascularization.

The researchers found that both obstructive and mild, or nonobstructive, coronary artery disease, as determined by CCTA, were associated with patient deaths and MACE. Most importantly, the researchers found that the relative risk for death or MACE for a patient with mild coronary artery disease was comparable to that of patients with single vessel obstructive disease.

“Until now, two-year follow-up studies suggested that a diabetic patient with mild or nonobstructive coronary artery disease had a lower risk of major adverse cardiovascular events and death than patients with obstructive disease,” said Philipp Blanke, MD, a radiologist at the University of British Columbia and St. Paul’s Hospital and a coauthor of the study. “Our five-year follow-up data suggest that nonobstructive and obstructive coronary artery disease, as detected by cardiac CTA in diabetic patients, are both associated with higher rates of mortality.”

Researchers need a better understanding of the evolution of plaque in the arteries and of patient response to therapies, said Dr. Leipsic. “Cardiac CT angiography is helpful for identifying diabetic patients who are at higher risk for heart events and who may benefit from more aggressive therapy to help modify that risk,” he added.

Patients Prefer Direct Access to Imaging Records
Patients value direct, independent access to their medical exams, researchers reported.

Giampaolo Greco, PhD, MPH, Assistant Professor in the Department of Population Health Science and Policy at the Mount Sinai School of Medicine in New York City, and colleagues set out to evaluate patient and provider satisfaction with RSNA Image Share, an Internet-based interoperable image exchange system that gives patients ownership of their imaging exams and control over access to their imaging records. The network enables radiology sites to make results of imaging exams available for patients to incorporate in personal health record (PHR) accounts they can use to securely store, manage, and share their imaging records. Sites also can use the network to send patient imaging records to other participating sites to support better informed care.

For the study, patients undergoing radiologic exams at four academic centers were eligible to establish online PHR accounts using the RSNA Image Share network. Patients could then use their PHR accounts to maintain and share their images with selected providers, creating a detailed medical history accessible through any secure Internet connection.

Between July 2012 and August 2013, the study enrolled 2,562 patients, mean age 50.4, including a significant representation of older individuals. Older individuals have the highest healthcare utilization and often experience or perceive a significant barrier in using information technology.

The median number of exams uploaded per patient was six. Study participants were provided a brief survey to assess patient and physician experience with the exchange of images, and 502 patients completed and returned their surveys. Of these respondents, 448 patients identified the method used at the visit to share images: Internet, CDs, both Internet and CDs, or other, and 165 included a section completed by their physician.

Nearly all (96%) of the patients responded positively to having direct access to their medical images, and 78% viewed their images independently. There was no difference between Internet and CD users in satisfaction with privacy and security and timeliness of access to medical images. A greater percentage of Internet users reported being able to access their images without difficulty, compared with CD users (88.3% vs 77.5%).

Patients receiving targeted anticancer treatments are at a significant risk of developing xerosis, or abnormal dryness, according to Dr. Johannah Valentine and her associates.

In a systematic review and meta-analysis of clinical trials involving 58 targeted agents, nearly 18% of all patients developed xerosis, with 1% of patients developing high-grade xerosis. The incidence may be affected by age, concomitant medications, comorbidities, and underlying malignancies or skin conditions, and reporting may vary among physicians and institutions, the researchers said.

Patients should be counseled and treated early for this symptom to prevent suboptimal dosing and quality-of-life impairment, the investigators recommended.

Read the full article at the Journal of the American Academy of Dermatology (doi:10.1016/j.jaad.2014.12.010).

Patients receiving targeted anticancer treatments are at a significant risk of developing xerosis, or abnormal dryness, according to Dr. Johannah Valentine and her associates.

In a systematic review and meta-analysis of clinical trials involving 58 targeted agents, nearly 18% of all patients developed xerosis, with 1% of patients developing high-grade xerosis. The incidence may be affected by age, concomitant medications, comorbidities, and underlying malignancies or skin conditions, and reporting may vary among physicians and institutions, the researchers said.

Patients should be counseled and treated early for this symptom to prevent suboptimal dosing and quality-of-life impairment, the investigators recommended.

Read the full article at the Journal of the American Academy of Dermatology (doi:10.1016/j.jaad.2014.12.010).

Patients receiving targeted anticancer treatments are at a significant risk of developing xerosis, or abnormal dryness, according to Dr. Johannah Valentine and her associates.

In a systematic review and meta-analysis of clinical trials involving 58 targeted agents, nearly 18% of all patients developed xerosis, with 1% of patients developing high-grade xerosis. The incidence may be affected by age, concomitant medications, comorbidities, and underlying malignancies or skin conditions, and reporting may vary among physicians and institutions, the researchers said.

Patients should be counseled and treated early for this symptom to prevent suboptimal dosing and quality-of-life impairment, the investigators recommended.

Read the full article at the Journal of the American Academy of Dermatology (doi:10.1016/j.jaad.2014.12.010).

Patient-safety guru Peter Pronovost, MD, PhD, senior vice president for patient safety and quality at Johns Hopkins Medicine in Baltimore, talks about hospitalists’ role in improving the American healthcare system.

Patient-safety guru Peter Pronovost, MD, PhD, senior vice president for patient safety and quality at Johns Hopkins Medicine in Baltimore, talks about hospitalists’ role in improving the American healthcare system.

Patient-safety guru Peter Pronovost, MD, PhD, senior vice president for patient safety and quality at Johns Hopkins Medicine in Baltimore, talks about hospitalists’ role in improving the American healthcare system.