CT scan showing a stroke

Credit: Lucien Monfils

Researchers say they’ve developed a technique that can predict—with 95% accuracy—which stroke patients will benefit from tissue-type plasminogen activator (tPA) and which will suffer from intracranial hemorrhage if treated.

The team devised a method that uses standard MRI scans to measure damage to the blood-brain barrier.

If further tests confirm the method’s accuracy, the researchers say it could allow for more precise use of intravenous tPA.

“If we are able to replicate our findings in more patients, it will indicate we are able to identify which people are likely to have bad outcomes, improving the drug’s safety and also potentially allowing us to give the drug to patients who currently go untreated,” said study author Richard Leigh, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

Dr Leigh and his colleagues described their technique in Stroke.

The group’s method is a computer program that lets physicians see how much gadolinium, the contrast material injected into a patient’s vein during an MRI scan, has leaked into the brain tissue from surrounding blood vessels.

By quantifying this damage in 75 stroke patients, the researchers identified a threshold for determining how much leakage was dangerous.

Then, they applied this threshold to those 75 records to determine how well it would predict who had suffered a brain hemorrhage and who had not. The test correctly predicted the outcome with 95% accuracy.

The researchers noted that, until now, physicians haven’t been able to predict with any precision which patients are likely to suffer a drug-related bleed and which are not. In these situations, if physicians knew the extent of the damage to the blood-brain barrier, they would be able to more safely administer treatment.

Typically, physicians do a CT scan of a stroke victim to see if he or she has visible bleeding before administering tPA. Dr Leigh said his computer program, which works with an MRI scan instead, can detect subtle changes to the blood-brain barrier that are otherwise impossible to see.

If his findings hold up, Dr Leigh said, “We should probably be doing MRI scans in every stroke patient before we give tPA.”

He conceded that an MRI scan does take longer to conduct in most institutions than a CT scan. But if the benefits of getting tPA into the right patients outweigh the harms of waiting a little longer to get MRI results, physicians should consider changing their practice, according to Dr Leigh.

“If we could eliminate all intracranial hemorrhages, it would be worth it,” he said.

Dr Leigh is now analyzing data from patients who received other treatments for stroke outside the typical time window, in some cases many hours after the FDA-approved cutoff for tPA. It’s possible, he said, that some patients who come to the hospital many hours after a stroke can still benefit from tPA, the only FDA-approved treatment for ischemic stroke.

CT scan showing a stroke

Credit: Lucien Monfils

Researchers say they’ve developed a technique that can predict—with 95% accuracy—which stroke patients will benefit from tissue-type plasminogen activator (tPA) and which will suffer from intracranial hemorrhage if treated.

The team devised a method that uses standard MRI scans to measure damage to the blood-brain barrier.

If further tests confirm the method’s accuracy, the researchers say it could allow for more precise use of intravenous tPA.

“If we are able to replicate our findings in more patients, it will indicate we are able to identify which people are likely to have bad outcomes, improving the drug’s safety and also potentially allowing us to give the drug to patients who currently go untreated,” said study author Richard Leigh, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

Dr Leigh and his colleagues described their technique in Stroke.

The group’s method is a computer program that lets physicians see how much gadolinium, the contrast material injected into a patient’s vein during an MRI scan, has leaked into the brain tissue from surrounding blood vessels.

By quantifying this damage in 75 stroke patients, the researchers identified a threshold for determining how much leakage was dangerous.

Then, they applied this threshold to those 75 records to determine how well it would predict who had suffered a brain hemorrhage and who had not. The test correctly predicted the outcome with 95% accuracy.

The researchers noted that, until now, physicians haven’t been able to predict with any precision which patients are likely to suffer a drug-related bleed and which are not. In these situations, if physicians knew the extent of the damage to the blood-brain barrier, they would be able to more safely administer treatment.

Typically, physicians do a CT scan of a stroke victim to see if he or she has visible bleeding before administering tPA. Dr Leigh said his computer program, which works with an MRI scan instead, can detect subtle changes to the blood-brain barrier that are otherwise impossible to see.

If his findings hold up, Dr Leigh said, “We should probably be doing MRI scans in every stroke patient before we give tPA.”

He conceded that an MRI scan does take longer to conduct in most institutions than a CT scan. But if the benefits of getting tPA into the right patients outweigh the harms of waiting a little longer to get MRI results, physicians should consider changing their practice, according to Dr Leigh.

“If we could eliminate all intracranial hemorrhages, it would be worth it,” he said.

Dr Leigh is now analyzing data from patients who received other treatments for stroke outside the typical time window, in some cases many hours after the FDA-approved cutoff for tPA. It’s possible, he said, that some patients who come to the hospital many hours after a stroke can still benefit from tPA, the only FDA-approved treatment for ischemic stroke.

CT scan showing a stroke

Credit: Lucien Monfils

Researchers say they’ve developed a technique that can predict—with 95% accuracy—which stroke patients will benefit from tissue-type plasminogen activator (tPA) and which will suffer from intracranial hemorrhage if treated.

The team devised a method that uses standard MRI scans to measure damage to the blood-brain barrier.

If further tests confirm the method’s accuracy, the researchers say it could allow for more precise use of intravenous tPA.

“If we are able to replicate our findings in more patients, it will indicate we are able to identify which people are likely to have bad outcomes, improving the drug’s safety and also potentially allowing us to give the drug to patients who currently go untreated,” said study author Richard Leigh, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

Dr Leigh and his colleagues described their technique in Stroke.

The group’s method is a computer program that lets physicians see how much gadolinium, the contrast material injected into a patient’s vein during an MRI scan, has leaked into the brain tissue from surrounding blood vessels.

By quantifying this damage in 75 stroke patients, the researchers identified a threshold for determining how much leakage was dangerous.

Then, they applied this threshold to those 75 records to determine how well it would predict who had suffered a brain hemorrhage and who had not. The test correctly predicted the outcome with 95% accuracy.

The researchers noted that, until now, physicians haven’t been able to predict with any precision which patients are likely to suffer a drug-related bleed and which are not. In these situations, if physicians knew the extent of the damage to the blood-brain barrier, they would be able to more safely administer treatment.

Typically, physicians do a CT scan of a stroke victim to see if he or she has visible bleeding before administering tPA. Dr Leigh said his computer program, which works with an MRI scan instead, can detect subtle changes to the blood-brain barrier that are otherwise impossible to see.

If his findings hold up, Dr Leigh said, “We should probably be doing MRI scans in every stroke patient before we give tPA.”

He conceded that an MRI scan does take longer to conduct in most institutions than a CT scan. But if the benefits of getting tPA into the right patients outweigh the harms of waiting a little longer to get MRI results, physicians should consider changing their practice, according to Dr Leigh.

“If we could eliminate all intracranial hemorrhages, it would be worth it,” he said.

Dr Leigh is now analyzing data from patients who received other treatments for stroke outside the typical time window, in some cases many hours after the FDA-approved cutoff for tPA. It’s possible, he said, that some patients who come to the hospital many hours after a stroke can still benefit from tPA, the only FDA-approved treatment for ischemic stroke.

Micrograph showing AML

The US Food and Drug Administration (FDA) has granted selinexor (KPT-330) orphan designation for the treatment of acute myeloid leukemia (AML).

Selinexor is a selective inhibitor of nuclear transport that functions by binding to the nuclear export protein XPO1 (also called CRM1).

This leads to the accumulation of tumor suppressor proteins in the cell nucleus, which is thought to cause apoptosis in cancer cells while largely sparing normal cells.

The FDA grants orphan designation to promote the development of drugs that target conditions affecting 200,000 or fewer US patients annually and are expected to provide significant therapeutic advantage over existing treatments.

Selinexor’s orphan designation qualifies the drug’s developer, Karyopharm Therapeutics, Inc., for benefits that apply across all stages of development, including an accelerated approval process, 7 years of market exclusivity following marketing approval, tax credits on US clinical trials, eligibility for orphan drug grants, and a waiver of certain administrative fees.

Promising early results

Selinexor has shown promising results in a phase 1 trial of older patients with relapsed or refractory AML. The study, which was sponsored by Karyopharm, was published in Blood.

Researchers enrolled 16 patients with relapsed or refractory AML. The median age was 71 years, and the median number of prior therapeutic regimens was 2.

Patients received 8 to 10 doses of selinexor on a 4-week cycle across 2 dose levels, 16.8 mg/m² to 23 mg/m² (with additional cohorts ongoing).

The researchers reported no dose-limiting toxicity, no clinically significant cumulative toxicities, and no major organ dysfunction.

However, 4 patients experienced drug-related grade 3/4 adverse events, including hypotension (n=1), increased AST (n=1), hypokalemia (n=1), nausea (n=1), headache (n=1), and fatigue (n=1).

The most common grade 1/2 toxicities were nausea (9/17; 53%), anorexia (8/17; 47%), vomiting (6/17; 35%), fatigue (5/17; 29%), weight loss (5/17; 29%), and diarrhea (3/17; 18%). But these events were manageable.

Fourteen of the patients were evaluable for response. Two (14%) achieved a complete response with full hematologic recovery, and 2 (14%) achieved a complete response without hematologic recovery. Four patients (29%) had stable disease for more than 30 days, and 6 (43%) experienced progression.

Other trials of selinexor in AML

Karyopharm’s development plans for selinexor in AML include a number of additional studies.

In a phase 2 trial, researchers will evaluate selinexor monotherapy in older patients with AML. The study will enroll patients 60 years of age or older with relapsed or refractory AML who are ineligible for intensive chemotherapy and/or transplant.

In another study, researchers will evaluate selinexor in combination with decitabine for patients with relapsed, refractory, or newly diagnosed AML. The study will enroll up to 42 patients aged 60 or older who are ineligible for intensive chemotherapy.

Lastly, researchers are planning a study of selinexor in pediatric leukemia patients. The goal of this study is to determine the oral dosing, toxicity, and preliminary clinical activity of selinexor in pediatric patients. It will enroll up to 28 children with relapsed or refractory AML or acute lymphoblastic leukemia.

Micrograph showing AML

The US Food and Drug Administration (FDA) has granted selinexor (KPT-330) orphan designation for the treatment of acute myeloid leukemia (AML).

Selinexor is a selective inhibitor of nuclear transport that functions by binding to the nuclear export protein XPO1 (also called CRM1).

This leads to the accumulation of tumor suppressor proteins in the cell nucleus, which is thought to cause apoptosis in cancer cells while largely sparing normal cells.

The FDA grants orphan designation to promote the development of drugs that target conditions affecting 200,000 or fewer US patients annually and are expected to provide significant therapeutic advantage over existing treatments.

Selinexor’s orphan designation qualifies the drug’s developer, Karyopharm Therapeutics, Inc., for benefits that apply across all stages of development, including an accelerated approval process, 7 years of market exclusivity following marketing approval, tax credits on US clinical trials, eligibility for orphan drug grants, and a waiver of certain administrative fees.

Promising early results

Selinexor has shown promising results in a phase 1 trial of older patients with relapsed or refractory AML. The study, which was sponsored by Karyopharm, was published in Blood.

Researchers enrolled 16 patients with relapsed or refractory AML. The median age was 71 years, and the median number of prior therapeutic regimens was 2.

Patients received 8 to 10 doses of selinexor on a 4-week cycle across 2 dose levels, 16.8 mg/m² to 23 mg/m² (with additional cohorts ongoing).

The researchers reported no dose-limiting toxicity, no clinically significant cumulative toxicities, and no major organ dysfunction.

However, 4 patients experienced drug-related grade 3/4 adverse events, including hypotension (n=1), increased AST (n=1), hypokalemia (n=1), nausea (n=1), headache (n=1), and fatigue (n=1).

The most common grade 1/2 toxicities were nausea (9/17; 53%), anorexia (8/17; 47%), vomiting (6/17; 35%), fatigue (5/17; 29%), weight loss (5/17; 29%), and diarrhea (3/17; 18%). But these events were manageable.

Fourteen of the patients were evaluable for response. Two (14%) achieved a complete response with full hematologic recovery, and 2 (14%) achieved a complete response without hematologic recovery. Four patients (29%) had stable disease for more than 30 days, and 6 (43%) experienced progression.

Other trials of selinexor in AML

Karyopharm’s development plans for selinexor in AML include a number of additional studies.

In a phase 2 trial, researchers will evaluate selinexor monotherapy in older patients with AML. The study will enroll patients 60 years of age or older with relapsed or refractory AML who are ineligible for intensive chemotherapy and/or transplant.

In another study, researchers will evaluate selinexor in combination with decitabine for patients with relapsed, refractory, or newly diagnosed AML. The study will enroll up to 42 patients aged 60 or older who are ineligible for intensive chemotherapy.

Lastly, researchers are planning a study of selinexor in pediatric leukemia patients. The goal of this study is to determine the oral dosing, toxicity, and preliminary clinical activity of selinexor in pediatric patients. It will enroll up to 28 children with relapsed or refractory AML or acute lymphoblastic leukemia.

Micrograph showing AML

The US Food and Drug Administration (FDA) has granted selinexor (KPT-330) orphan designation for the treatment of acute myeloid leukemia (AML).

Selinexor is a selective inhibitor of nuclear transport that functions by binding to the nuclear export protein XPO1 (also called CRM1).

This leads to the accumulation of tumor suppressor proteins in the cell nucleus, which is thought to cause apoptosis in cancer cells while largely sparing normal cells.

The FDA grants orphan designation to promote the development of drugs that target conditions affecting 200,000 or fewer US patients annually and are expected to provide significant therapeutic advantage over existing treatments.

Selinexor’s orphan designation qualifies the drug’s developer, Karyopharm Therapeutics, Inc., for benefits that apply across all stages of development, including an accelerated approval process, 7 years of market exclusivity following marketing approval, tax credits on US clinical trials, eligibility for orphan drug grants, and a waiver of certain administrative fees.

Promising early results

Selinexor has shown promising results in a phase 1 trial of older patients with relapsed or refractory AML. The study, which was sponsored by Karyopharm, was published in Blood.

Researchers enrolled 16 patients with relapsed or refractory AML. The median age was 71 years, and the median number of prior therapeutic regimens was 2.

Patients received 8 to 10 doses of selinexor on a 4-week cycle across 2 dose levels, 16.8 mg/m² to 23 mg/m² (with additional cohorts ongoing).

The researchers reported no dose-limiting toxicity, no clinically significant cumulative toxicities, and no major organ dysfunction.

However, 4 patients experienced drug-related grade 3/4 adverse events, including hypotension (n=1), increased AST (n=1), hypokalemia (n=1), nausea (n=1), headache (n=1), and fatigue (n=1).

The most common grade 1/2 toxicities were nausea (9/17; 53%), anorexia (8/17; 47%), vomiting (6/17; 35%), fatigue (5/17; 29%), weight loss (5/17; 29%), and diarrhea (3/17; 18%). But these events were manageable.

Fourteen of the patients were evaluable for response. Two (14%) achieved a complete response with full hematologic recovery, and 2 (14%) achieved a complete response without hematologic recovery. Four patients (29%) had stable disease for more than 30 days, and 6 (43%) experienced progression.

Other trials of selinexor in AML

Karyopharm’s development plans for selinexor in AML include a number of additional studies.

In a phase 2 trial, researchers will evaluate selinexor monotherapy in older patients with AML. The study will enroll patients 60 years of age or older with relapsed or refractory AML who are ineligible for intensive chemotherapy and/or transplant.

In another study, researchers will evaluate selinexor in combination with decitabine for patients with relapsed, refractory, or newly diagnosed AML. The study will enroll up to 42 patients aged 60 or older who are ineligible for intensive chemotherapy.

Lastly, researchers are planning a study of selinexor in pediatric leukemia patients. The goal of this study is to determine the oral dosing, toxicity, and preliminary clinical activity of selinexor in pediatric patients. It will enroll up to 28 children with relapsed or refractory AML or acute lymphoblastic leukemia.

Hear from:

Michael Baggish, MD (St. Helena, California)

Rupen Baxi, MD (Royal Oak, Michigan)

Jennifer Hollings, MD (Richmond, Virginia)

Gwinnett Ladson, MD (Nashville, Tennessee)

Rich Persino, MD (McHenry, Illinois)

Teresa Tam, MD (Chicago, Illinois)

Yvonne Wolny, MD (Chicago, Illinois)

Hear from:

Michael Baggish, MD (St. Helena, California)

Rupen Baxi, MD (Royal Oak, Michigan)

Jennifer Hollings, MD (Richmond, Virginia)

Gwinnett Ladson, MD (Nashville, Tennessee)

Rich Persino, MD (McHenry, Illinois)

Teresa Tam, MD (Chicago, Illinois)

Yvonne Wolny, MD (Chicago, Illinois)

Hear from:

Michael Baggish, MD (St. Helena, California)

Rupen Baxi, MD (Royal Oak, Michigan)

Jennifer Hollings, MD (Richmond, Virginia)

Gwinnett Ladson, MD (Nashville, Tennessee)

Rich Persino, MD (McHenry, Illinois)

Teresa Tam, MD (Chicago, Illinois)

Yvonne Wolny, MD (Chicago, Illinois)

The spectrum of idiopathic ultraviolet-induced dermatoses includes the most severe variant, polymorphous light eruption (PMLE), in which erythematous papules, papulovesicles, and plaques form from a delayed type IV hypersensitivity reaction to the sun. Its milder cousins, benign summer light eruption and juvenile springtime eruption, are milder, more transient variants.

Patients may experience sudden-onset, pruritic, sometimes painful papules and papulovesicles or cheilitis within 30 minutes to several hours of exposure to UV light in areas normally covered in the winter months. The rash subsides over 1-7 days (or sooner with effective topical steroid administration and strict sun avoidance) and without scarring. Occasionally, patients experience systemic flulike symptoms after sun exposure. Triggers can be UVA, UVB, or UVC. However, because most cases appear in the spring, describing these variants as benign summer light eruption is something of a misnomer.

These seasonal rashes are often underrecognized in skin of color patients, particularly those with Fitzpatrick skin types III-VI, because many practitioners assume a protective role of melanin (Photochem. Photobiol. Sci. 2013;12:65-77). A study by Kerr and Lim identified 280 patients with photodermatoses; 135 (48%) were African American, 110 (40%) were white, and 35 (12%) were other ethnicities. They noted a significantly higher proportion of African Americans with PMLE, compared with whites (J. Am. Acad. Dermatol. 2007;57:638-43). Also, Native Americans have a hereditary form of PMLE with autosomal dominant inheritance that can involve the face and is most common in patients with Fitzpatrick skin types III-VI.

For sun-sensitive patients, and especially skin of color patients, diagnosis and treatment include ruling out other photosensitive diseases such as systemic lupus, and then counseling about the importance of sun avoidance and the use of sunscreens, which include both UVA and UVB protection. Prophylactic phototherapy or photochemotherapy at the beginning of spring for several weeks may prevent flare-ups throughout the summer. PUVA (psoralen and UVA) therapy, as well as UVB phototherapy, have been successful at preventing flares in several studies. Topical steroids, antihistamines, and oral prednisone are mainstays of treatment for severe flares, alone or in combination with phototherapy. For severe cases, or those recalcitrant to first-line treatment, antimalarials, azathioprine, and thalidomide have been used with variable efficacy.

Particularly at this time of year, I always ask patients with photo-distributed rashes about their ethnicities. One can never assume ethnicity, culture, skin type, background, or even photosensitivity based on skin color alone. I have been surprised by the many patients with dark skin who may have Native American origins who present with photosensitive rashes, or the many patients with hereditary photosensitive rashes with fair skin. Our beautiful, multicultural society makes it harder to define or categorize dermatoses by skin type alone, based on the definitions we have set for skin type in our literature today.

Dr. Talakoub and Dr. Wesley are co-contributors to a monthly Aesthetic Dermatology column in Skin & Allergy News. Dr. Talakoub is in private practice at McLean (Va.) Dermatology Center. Dr. Wesley practices dermatology in Beverly Hills, Calif.

The spectrum of idiopathic ultraviolet-induced dermatoses includes the most severe variant, polymorphous light eruption (PMLE), in which erythematous papules, papulovesicles, and plaques form from a delayed type IV hypersensitivity reaction to the sun. Its milder cousins, benign summer light eruption and juvenile springtime eruption, are milder, more transient variants.

Patients may experience sudden-onset, pruritic, sometimes painful papules and papulovesicles or cheilitis within 30 minutes to several hours of exposure to UV light in areas normally covered in the winter months. The rash subsides over 1-7 days (or sooner with effective topical steroid administration and strict sun avoidance) and without scarring. Occasionally, patients experience systemic flulike symptoms after sun exposure. Triggers can be UVA, UVB, or UVC. However, because most cases appear in the spring, describing these variants as benign summer light eruption is something of a misnomer.

These seasonal rashes are often underrecognized in skin of color patients, particularly those with Fitzpatrick skin types III-VI, because many practitioners assume a protective role of melanin (Photochem. Photobiol. Sci. 2013;12:65-77). A study by Kerr and Lim identified 280 patients with photodermatoses; 135 (48%) were African American, 110 (40%) were white, and 35 (12%) were other ethnicities. They noted a significantly higher proportion of African Americans with PMLE, compared with whites (J. Am. Acad. Dermatol. 2007;57:638-43). Also, Native Americans have a hereditary form of PMLE with autosomal dominant inheritance that can involve the face and is most common in patients with Fitzpatrick skin types III-VI.

For sun-sensitive patients, and especially skin of color patients, diagnosis and treatment include ruling out other photosensitive diseases such as systemic lupus, and then counseling about the importance of sun avoidance and the use of sunscreens, which include both UVA and UVB protection. Prophylactic phototherapy or photochemotherapy at the beginning of spring for several weeks may prevent flare-ups throughout the summer. PUVA (psoralen and UVA) therapy, as well as UVB phototherapy, have been successful at preventing flares in several studies. Topical steroids, antihistamines, and oral prednisone are mainstays of treatment for severe flares, alone or in combination with phototherapy. For severe cases, or those recalcitrant to first-line treatment, antimalarials, azathioprine, and thalidomide have been used with variable efficacy.

Particularly at this time of year, I always ask patients with photo-distributed rashes about their ethnicities. One can never assume ethnicity, culture, skin type, background, or even photosensitivity based on skin color alone. I have been surprised by the many patients with dark skin who may have Native American origins who present with photosensitive rashes, or the many patients with hereditary photosensitive rashes with fair skin. Our beautiful, multicultural society makes it harder to define or categorize dermatoses by skin type alone, based on the definitions we have set for skin type in our literature today.

Dr. Talakoub and Dr. Wesley are co-contributors to a monthly Aesthetic Dermatology column in Skin & Allergy News. Dr. Talakoub is in private practice at McLean (Va.) Dermatology Center. Dr. Wesley practices dermatology in Beverly Hills, Calif.

The spectrum of idiopathic ultraviolet-induced dermatoses includes the most severe variant, polymorphous light eruption (PMLE), in which erythematous papules, papulovesicles, and plaques form from a delayed type IV hypersensitivity reaction to the sun. Its milder cousins, benign summer light eruption and juvenile springtime eruption, are milder, more transient variants.

Patients may experience sudden-onset, pruritic, sometimes painful papules and papulovesicles or cheilitis within 30 minutes to several hours of exposure to UV light in areas normally covered in the winter months. The rash subsides over 1-7 days (or sooner with effective topical steroid administration and strict sun avoidance) and without scarring. Occasionally, patients experience systemic flulike symptoms after sun exposure. Triggers can be UVA, UVB, or UVC. However, because most cases appear in the spring, describing these variants as benign summer light eruption is something of a misnomer.

These seasonal rashes are often underrecognized in skin of color patients, particularly those with Fitzpatrick skin types III-VI, because many practitioners assume a protective role of melanin (Photochem. Photobiol. Sci. 2013;12:65-77). A study by Kerr and Lim identified 280 patients with photodermatoses; 135 (48%) were African American, 110 (40%) were white, and 35 (12%) were other ethnicities. They noted a significantly higher proportion of African Americans with PMLE, compared with whites (J. Am. Acad. Dermatol. 2007;57:638-43). Also, Native Americans have a hereditary form of PMLE with autosomal dominant inheritance that can involve the face and is most common in patients with Fitzpatrick skin types III-VI.

For sun-sensitive patients, and especially skin of color patients, diagnosis and treatment include ruling out other photosensitive diseases such as systemic lupus, and then counseling about the importance of sun avoidance and the use of sunscreens, which include both UVA and UVB protection. Prophylactic phototherapy or photochemotherapy at the beginning of spring for several weeks may prevent flare-ups throughout the summer. PUVA (psoralen and UVA) therapy, as well as UVB phototherapy, have been successful at preventing flares in several studies. Topical steroids, antihistamines, and oral prednisone are mainstays of treatment for severe flares, alone or in combination with phototherapy. For severe cases, or those recalcitrant to first-line treatment, antimalarials, azathioprine, and thalidomide have been used with variable efficacy.

Particularly at this time of year, I always ask patients with photo-distributed rashes about their ethnicities. One can never assume ethnicity, culture, skin type, background, or even photosensitivity based on skin color alone. I have been surprised by the many patients with dark skin who may have Native American origins who present with photosensitive rashes, or the many patients with hereditary photosensitive rashes with fair skin. Our beautiful, multicultural society makes it harder to define or categorize dermatoses by skin type alone, based on the definitions we have set for skin type in our literature today.

Dr. Talakoub and Dr. Wesley are co-contributors to a monthly Aesthetic Dermatology column in Skin & Allergy News. Dr. Talakoub is in private practice at McLean (Va.) Dermatology Center. Dr. Wesley practices dermatology in Beverly Hills, Calif.

NEW YORK – Outcomes of thoracoabdominal aortic aneurysm (TAAA) repair in octogenarians vary considerably with the extent of repair. Those who undergo Extent II TAAA repair have significantly higher risks of morbidity and mortality, while Extent I, III, and IV repairs can be performed with relatively good outcomes, according to Dr. Muhammad Aftab, who presented the findings at the meeting sponsored by the American Association for Thoracic Surgery.

"Extensive TAAA repair should be performed with caution in octogenarians," says Dr. Aftab, a Fellow in cardiothoracic surgery at the Baylor College of Medicine–Texas Heart Institute, Houston. He recommends that a thorough preoperative discussion to assess the risks and benefits with the patient and his family is necessary before proceeding with surgery.

In this retrospective review of patients seen between January 2005 and September 2013, octogenarians with thoracoabdominal aortic aneurysms (TAAAs) (n = 88) were compared with a younger cohort (n = 1,179 patients, aged 70 years). Dr. Aftab found that octogenarians were threefold more likely to present with aneurysm rupture (13.6% vs. 4.6%; P less than .001) but less likely to present with aortic dissections (12.5% vs. 43.9%; P less than .001) than did the younger patients.

During surgery, the use of other types of adjunctive interventions, such as left heart bypass, cerebrospinal fluid drainage, cold renal perfusion, and visceral perfusion differed significantly among the octogenarians based on the extent of repair and clinical condition (all P less than .001). Because the octogenarians had a greater atherosclerotic burden and higher incidence of renal and mesenteric occlusive disease, they were also more likely to require renal/visceral endarterectomy, stenting, or both (57.9% vs. 33.6%; P less than.001).

Overall, octogenarians had higher rates of operative mortality (26.1% vs. 6.9%), in-hospital deaths (25% vs. 6.4%), 30-day deaths (13.6% vs. 4.8%), and adverse outcomes (36.4% vs. 15.7%; P less than .001) than did the younger group, all significant differences. The outcomes included significantly higher rates of permanent renal failure, cardiac complications, and pulmonary complications. The octogenarians had longer recovery times, as suggested by longer postoperative ICU and hospital stays. Spinal cord deficits and paraplegia were higher in the older group, but the difference was not significant.

Poor outcomes differed according to the extent of surgery, and seemed to be exacerbated for those who underwent repair of Extent II aneurysms (according to the Crawford Classification, these involve the subclavian artery and extend to the bifurcation of the aorta in the pelvis). For instance, the Extent II group had the highest risk of operative mortality (61.5%) vs. Extent I (31.6%), III (21.4%), and IV (10.7%), a significant difference. The Extent II group also had much higher rates of in-hospital and 30-day death rates. The most common causes of deaths for the Extent II octogenarians were multisystem organ failure and cardiac problems.

Adverse outcomes were also significantly much higher for the Extent II group (76.9%) than for the other groups (42.1%, 28.6%, and 21.4%). Similar patterns were found for permanent paraplegia, renal failure requiring permanent dialysis, stroke, and days spent in the ICU. Almost 85% of those who required Extent II repair needed renal/visceral endarterectomy, stenting, or both as a part of the surgical procedure.

Extent II TAAA repair was identified as an independent predictor of perioperative mortality by multivariate analysis, conferring an 11-fold increased risk of death. Aneurysm rupture and dissection were also identified as predictors of perioperative mortality while only Extent II TAAA and dissection were independent predictors of adverse outcomes.

While these problems were exacerbated in those with Extent II repairs, Extent I, III, and IV TAAA repairs may be performed with relatively low risk, according to Dr. Aftab. The results suggest that while octogenarians present more challenges than younger individuals, outcomes vary greatly according to the type of aneurysm repair.

Dr. Aftab had no relevant disclosures.

NEW YORK – Outcomes of thoracoabdominal aortic aneurysm (TAAA) repair in octogenarians vary considerably with the extent of repair. Those who undergo Extent II TAAA repair have significantly higher risks of morbidity and mortality, while Extent I, III, and IV repairs can be performed with relatively good outcomes, according to Dr. Muhammad Aftab, who presented the findings at the meeting sponsored by the American Association for Thoracic Surgery.

"Extensive TAAA repair should be performed with caution in octogenarians," says Dr. Aftab, a Fellow in cardiothoracic surgery at the Baylor College of Medicine–Texas Heart Institute, Houston. He recommends that a thorough preoperative discussion to assess the risks and benefits with the patient and his family is necessary before proceeding with surgery.

In this retrospective review of patients seen between January 2005 and September 2013, octogenarians with thoracoabdominal aortic aneurysms (TAAAs) (n = 88) were compared with a younger cohort (n = 1,179 patients, aged 70 years). Dr. Aftab found that octogenarians were threefold more likely to present with aneurysm rupture (13.6% vs. 4.6%; P less than .001) but less likely to present with aortic dissections (12.5% vs. 43.9%; P less than .001) than did the younger patients.

During surgery, the use of other types of adjunctive interventions, such as left heart bypass, cerebrospinal fluid drainage, cold renal perfusion, and visceral perfusion differed significantly among the octogenarians based on the extent of repair and clinical condition (all P less than .001). Because the octogenarians had a greater atherosclerotic burden and higher incidence of renal and mesenteric occlusive disease, they were also more likely to require renal/visceral endarterectomy, stenting, or both (57.9% vs. 33.6%; P less than.001).

Overall, octogenarians had higher rates of operative mortality (26.1% vs. 6.9%), in-hospital deaths (25% vs. 6.4%), 30-day deaths (13.6% vs. 4.8%), and adverse outcomes (36.4% vs. 15.7%; P less than .001) than did the younger group, all significant differences. The outcomes included significantly higher rates of permanent renal failure, cardiac complications, and pulmonary complications. The octogenarians had longer recovery times, as suggested by longer postoperative ICU and hospital stays. Spinal cord deficits and paraplegia were higher in the older group, but the difference was not significant.

Poor outcomes differed according to the extent of surgery, and seemed to be exacerbated for those who underwent repair of Extent II aneurysms (according to the Crawford Classification, these involve the subclavian artery and extend to the bifurcation of the aorta in the pelvis). For instance, the Extent II group had the highest risk of operative mortality (61.5%) vs. Extent I (31.6%), III (21.4%), and IV (10.7%), a significant difference. The Extent II group also had much higher rates of in-hospital and 30-day death rates. The most common causes of deaths for the Extent II octogenarians were multisystem organ failure and cardiac problems.

Adverse outcomes were also significantly much higher for the Extent II group (76.9%) than for the other groups (42.1%, 28.6%, and 21.4%). Similar patterns were found for permanent paraplegia, renal failure requiring permanent dialysis, stroke, and days spent in the ICU. Almost 85% of those who required Extent II repair needed renal/visceral endarterectomy, stenting, or both as a part of the surgical procedure.

Extent II TAAA repair was identified as an independent predictor of perioperative mortality by multivariate analysis, conferring an 11-fold increased risk of death. Aneurysm rupture and dissection were also identified as predictors of perioperative mortality while only Extent II TAAA and dissection were independent predictors of adverse outcomes.

While these problems were exacerbated in those with Extent II repairs, Extent I, III, and IV TAAA repairs may be performed with relatively low risk, according to Dr. Aftab. The results suggest that while octogenarians present more challenges than younger individuals, outcomes vary greatly according to the type of aneurysm repair.

Dr. Aftab had no relevant disclosures.

NEW YORK – Outcomes of thoracoabdominal aortic aneurysm (TAAA) repair in octogenarians vary considerably with the extent of repair. Those who undergo Extent II TAAA repair have significantly higher risks of morbidity and mortality, while Extent I, III, and IV repairs can be performed with relatively good outcomes, according to Dr. Muhammad Aftab, who presented the findings at the meeting sponsored by the American Association for Thoracic Surgery.

"Extensive TAAA repair should be performed with caution in octogenarians," says Dr. Aftab, a Fellow in cardiothoracic surgery at the Baylor College of Medicine–Texas Heart Institute, Houston. He recommends that a thorough preoperative discussion to assess the risks and benefits with the patient and his family is necessary before proceeding with surgery.

In this retrospective review of patients seen between January 2005 and September 2013, octogenarians with thoracoabdominal aortic aneurysms (TAAAs) (n = 88) were compared with a younger cohort (n = 1,179 patients, aged 70 years). Dr. Aftab found that octogenarians were threefold more likely to present with aneurysm rupture (13.6% vs. 4.6%; P less than .001) but less likely to present with aortic dissections (12.5% vs. 43.9%; P less than .001) than did the younger patients.

During surgery, the use of other types of adjunctive interventions, such as left heart bypass, cerebrospinal fluid drainage, cold renal perfusion, and visceral perfusion differed significantly among the octogenarians based on the extent of repair and clinical condition (all P less than .001). Because the octogenarians had a greater atherosclerotic burden and higher incidence of renal and mesenteric occlusive disease, they were also more likely to require renal/visceral endarterectomy, stenting, or both (57.9% vs. 33.6%; P less than.001).

Overall, octogenarians had higher rates of operative mortality (26.1% vs. 6.9%), in-hospital deaths (25% vs. 6.4%), 30-day deaths (13.6% vs. 4.8%), and adverse outcomes (36.4% vs. 15.7%; P less than .001) than did the younger group, all significant differences. The outcomes included significantly higher rates of permanent renal failure, cardiac complications, and pulmonary complications. The octogenarians had longer recovery times, as suggested by longer postoperative ICU and hospital stays. Spinal cord deficits and paraplegia were higher in the older group, but the difference was not significant.

Poor outcomes differed according to the extent of surgery, and seemed to be exacerbated for those who underwent repair of Extent II aneurysms (according to the Crawford Classification, these involve the subclavian artery and extend to the bifurcation of the aorta in the pelvis). For instance, the Extent II group had the highest risk of operative mortality (61.5%) vs. Extent I (31.6%), III (21.4%), and IV (10.7%), a significant difference. The Extent II group also had much higher rates of in-hospital and 30-day death rates. The most common causes of deaths for the Extent II octogenarians were multisystem organ failure and cardiac problems.

Adverse outcomes were also significantly much higher for the Extent II group (76.9%) than for the other groups (42.1%, 28.6%, and 21.4%). Similar patterns were found for permanent paraplegia, renal failure requiring permanent dialysis, stroke, and days spent in the ICU. Almost 85% of those who required Extent II repair needed renal/visceral endarterectomy, stenting, or both as a part of the surgical procedure.

Extent II TAAA repair was identified as an independent predictor of perioperative mortality by multivariate analysis, conferring an 11-fold increased risk of death. Aneurysm rupture and dissection were also identified as predictors of perioperative mortality while only Extent II TAAA and dissection were independent predictors of adverse outcomes.

While these problems were exacerbated in those with Extent II repairs, Extent I, III, and IV TAAA repairs may be performed with relatively low risk, according to Dr. Aftab. The results suggest that while octogenarians present more challenges than younger individuals, outcomes vary greatly according to the type of aneurysm repair.

Dr. Aftab had no relevant disclosures.

Clostridium difficile colonies

on a blood agar plate

Credit: CDC

BOSTON—Results of a phase 2 study suggest an investigational vaccine may be able to prevent Clostridium difficile infection (CDI).

The vaccine generated an immune response against C difficile toxins A and B. And adverse reactions were generally mild and of short duration.

Researchers presented these results at the 114th General Meeting of the American Society for Microbiology. The study was sponsored by Sanofi, the company developing the vaccine.

“C diff infection threatens the many people who frequently use antibiotics, as well as older hospitalized patients and residents in long-term healthcare facilities,” said study investigator Jamshid Saleh, MD of the Northern California Clinical Research Center in Redding, California.

“It would be great if we could offer patients a way to help prevent this contagious and debilitating disease versus just treating it after it happens.”

To find out if Sanofi’s vaccine would do the job, Dr Saleh and his colleagues conducted a randomized, multicenter trial split into 2 stages.

The first stage, conducted with 455 volunteers, was placebo-controlled, double-blind, and designed for dose and formulation selection. The second stage, which included 206 additional volunteers, was designed to compare the dose and formulation chosen in the first stage against 2 alternate dosing schedules.

Volunteers ranged in age from 40 to 75 years and were at risk of CDI due to impending hospitalization or residence in a long-term healthcare facility.

In stage 1, volunteers were randomized into 1 of 5 study groups: high-dose or low-dose vaccine, either with or without adjuvant, or placebo. Each formulation was administered on days 0, 7, and 30.

Researchers measured immune responses using both enzyme linked immunosorbent assay (ELISA), which assesses antitoxin A and B immunoglobulin G (IgG) concentrations, and toxin neutralization activity (TNA), which measures antitoxin A and B neutralizing activity.

Composite ELISA ranking analysis determined that the high-dose plus adjuvant vaccine formulation (group 3) generated the greatest immune response over a 60-day period. ELISA results also showed a 4-fold increase in the development of detectable antibodies for both toxins A and B.

So the researchers selected the high-dose plus adjuvant vaccine formulation for further study in stage 2 of the trial. They compared its use across 3 schedules: days 0, 7, and 30 (group 3, n=101); days 0, 7, and 180 (group 6, n=103); and days 0, 30, and 180 (group 7, n=103). The team analyzed subjects on days 0, 7, 14, 30, 60, 180, and 210.

There were increased immune responses in all vaccine groups and with each dose, according to ELISA and TNA. Overall, group 3 demonstrated the most favorable immune profile over the 30-, 60- and 180-day periods, particularly in volunteers aged 65-75 years.

The safety profile of all vaccine doses was deemed acceptable throughout the study. Reactions were monitored until day 210 and were generally grade 1, of short duration, did not lead to study discontinuation, and were not considered clinically significant.

“Sanofi Pasteur’s investigational vaccine stimulates a person’s immune system to fight C diff toxins upon exposure and, ultimately, may help prevent a future CDI from occurring,” Dr Saleh said.

“Like other toxoid vaccines—such as tetanus, diphtheria, and whooping cough—this investigational vaccine targets the symptom-causing toxins generated by C diff bacteria and could be an important public health measure to help protect individuals from CDI.”

Based on the phase 2 results, researchers started a phase 3 trial in August 2013.

Clostridium difficile colonies

on a blood agar plate

Credit: CDC

BOSTON—Results of a phase 2 study suggest an investigational vaccine may be able to prevent Clostridium difficile infection (CDI).

The vaccine generated an immune response against C difficile toxins A and B. And adverse reactions were generally mild and of short duration.

Researchers presented these results at the 114th General Meeting of the American Society for Microbiology. The study was sponsored by Sanofi, the company developing the vaccine.

“C diff infection threatens the many people who frequently use antibiotics, as well as older hospitalized patients and residents in long-term healthcare facilities,” said study investigator Jamshid Saleh, MD of the Northern California Clinical Research Center in Redding, California.

“It would be great if we could offer patients a way to help prevent this contagious and debilitating disease versus just treating it after it happens.”

To find out if Sanofi’s vaccine would do the job, Dr Saleh and his colleagues conducted a randomized, multicenter trial split into 2 stages.

The first stage, conducted with 455 volunteers, was placebo-controlled, double-blind, and designed for dose and formulation selection. The second stage, which included 206 additional volunteers, was designed to compare the dose and formulation chosen in the first stage against 2 alternate dosing schedules.

Volunteers ranged in age from 40 to 75 years and were at risk of CDI due to impending hospitalization or residence in a long-term healthcare facility.

In stage 1, volunteers were randomized into 1 of 5 study groups: high-dose or low-dose vaccine, either with or without adjuvant, or placebo. Each formulation was administered on days 0, 7, and 30.

Researchers measured immune responses using both enzyme linked immunosorbent assay (ELISA), which assesses antitoxin A and B immunoglobulin G (IgG) concentrations, and toxin neutralization activity (TNA), which measures antitoxin A and B neutralizing activity.

Composite ELISA ranking analysis determined that the high-dose plus adjuvant vaccine formulation (group 3) generated the greatest immune response over a 60-day period. ELISA results also showed a 4-fold increase in the development of detectable antibodies for both toxins A and B.

So the researchers selected the high-dose plus adjuvant vaccine formulation for further study in stage 2 of the trial. They compared its use across 3 schedules: days 0, 7, and 30 (group 3, n=101); days 0, 7, and 180 (group 6, n=103); and days 0, 30, and 180 (group 7, n=103). The team analyzed subjects on days 0, 7, 14, 30, 60, 180, and 210.

There were increased immune responses in all vaccine groups and with each dose, according to ELISA and TNA. Overall, group 3 demonstrated the most favorable immune profile over the 30-, 60- and 180-day periods, particularly in volunteers aged 65-75 years.

The safety profile of all vaccine doses was deemed acceptable throughout the study. Reactions were monitored until day 210 and were generally grade 1, of short duration, did not lead to study discontinuation, and were not considered clinically significant.

“Sanofi Pasteur’s investigational vaccine stimulates a person’s immune system to fight C diff toxins upon exposure and, ultimately, may help prevent a future CDI from occurring,” Dr Saleh said.

“Like other toxoid vaccines—such as tetanus, diphtheria, and whooping cough—this investigational vaccine targets the symptom-causing toxins generated by C diff bacteria and could be an important public health measure to help protect individuals from CDI.”

Based on the phase 2 results, researchers started a phase 3 trial in August 2013.

Clostridium difficile colonies

on a blood agar plate

Credit: CDC

BOSTON—Results of a phase 2 study suggest an investigational vaccine may be able to prevent Clostridium difficile infection (CDI).

The vaccine generated an immune response against C difficile toxins A and B. And adverse reactions were generally mild and of short duration.

Researchers presented these results at the 114th General Meeting of the American Society for Microbiology. The study was sponsored by Sanofi, the company developing the vaccine.

“C diff infection threatens the many people who frequently use antibiotics, as well as older hospitalized patients and residents in long-term healthcare facilities,” said study investigator Jamshid Saleh, MD of the Northern California Clinical Research Center in Redding, California.

“It would be great if we could offer patients a way to help prevent this contagious and debilitating disease versus just treating it after it happens.”

To find out if Sanofi’s vaccine would do the job, Dr Saleh and his colleagues conducted a randomized, multicenter trial split into 2 stages.

The first stage, conducted with 455 volunteers, was placebo-controlled, double-blind, and designed for dose and formulation selection. The second stage, which included 206 additional volunteers, was designed to compare the dose and formulation chosen in the first stage against 2 alternate dosing schedules.

Volunteers ranged in age from 40 to 75 years and were at risk of CDI due to impending hospitalization or residence in a long-term healthcare facility.

In stage 1, volunteers were randomized into 1 of 5 study groups: high-dose or low-dose vaccine, either with or without adjuvant, or placebo. Each formulation was administered on days 0, 7, and 30.

Researchers measured immune responses using both enzyme linked immunosorbent assay (ELISA), which assesses antitoxin A and B immunoglobulin G (IgG) concentrations, and toxin neutralization activity (TNA), which measures antitoxin A and B neutralizing activity.

Composite ELISA ranking analysis determined that the high-dose plus adjuvant vaccine formulation (group 3) generated the greatest immune response over a 60-day period. ELISA results also showed a 4-fold increase in the development of detectable antibodies for both toxins A and B.

So the researchers selected the high-dose plus adjuvant vaccine formulation for further study in stage 2 of the trial. They compared its use across 3 schedules: days 0, 7, and 30 (group 3, n=101); days 0, 7, and 180 (group 6, n=103); and days 0, 30, and 180 (group 7, n=103). The team analyzed subjects on days 0, 7, 14, 30, 60, 180, and 210.

There were increased immune responses in all vaccine groups and with each dose, according to ELISA and TNA. Overall, group 3 demonstrated the most favorable immune profile over the 30-, 60- and 180-day periods, particularly in volunteers aged 65-75 years.

The safety profile of all vaccine doses was deemed acceptable throughout the study. Reactions were monitored until day 210 and were generally grade 1, of short duration, did not lead to study discontinuation, and were not considered clinically significant.

“Sanofi Pasteur’s investigational vaccine stimulates a person’s immune system to fight C diff toxins upon exposure and, ultimately, may help prevent a future CDI from occurring,” Dr Saleh said.

“Like other toxoid vaccines—such as tetanus, diphtheria, and whooping cough—this investigational vaccine targets the symptom-causing toxins generated by C diff bacteria and could be an important public health measure to help protect individuals from CDI.”

Based on the phase 2 results, researchers started a phase 3 trial in August 2013.

Blood vessels

SAN DIEGO—Taking olive oil supplements may counteract some of the adverse cardiovascular effects of air pollution, according to a new study.

“Exposure to airborne particulate matter can lead to endothelial dysfunction, a condition in which the endothelium of blood vessels does not function normally, which is a risk factor for clinical cardiovascular events and progression of atherosclerosis,” said Haiyan Tong,

MD, PhD, of the US Environmental Protection Agency.

“As olive oil and fish oil are known to have beneficial effects on endothelial dysfunction, we examined whether use of these supplements would counteract the adverse cardiovascular effects of exposure to concentrated ambient particulate matter in a controlled setting.”

Dr Tong and his colleagues presented their findings at the American Thoracic Society’s 2014 International Conference (abstract 55100).

Their study involved 42 healthy adults who were randomized to receive 3 g/day of olive oil, fish oil, or no supplements for 4 weeks. Subjects then underwent controlled, 2-hour exposures to filtered air, followed on the next day by exposure to fine/ultrafine concentrated ambient particulate matter (CAP, mean mass concentration 253±16 µg/m³) in a controlled-exposure chamber.

The researchers assessed endothelial function by sonographic measurement of flow-mediated dilation of the brachial artery before, immediately after, and 20 hours after exposure to air and CAP. They also measured blood markers of vasoconstriction and fibrinolysis.

Immediately after exposure to CAP, there were significant particulate matter mass-dependent reductions in flow-mediated dilation in the control group (-19.4±8.4% per 100 µg/m³ increase in CAP concentration relative to pre-filtered air levels) and the fish oil group (-13.7±5.3%), but the decrease in the olive oil group was not significant (-7.6±6.8%).

Tissue plasminogen activator increased immediately after CAP exposure in the olive oil group (11.6±5%), and this effect persisted for up to 20 hours.

Olive oil supplementation also ameliorated changes in blood markers associated with vasoconstriction and fibrinolysis, while fish oil supplementation had no effect on endothelial function or fibrinolysis after CAP exposure.

“Our study suggests that use of olive oil supplements may protect against the adverse vascular effects of exposure to air pollution particles,” Dr Tong said. “If these results are replicated in further studies, use of these supplements might offer a safe, low-cost, and effective means of counteracting some of the health consequences of exposure to air pollution.”

Blood vessels

SAN DIEGO—Taking olive oil supplements may counteract some of the adverse cardiovascular effects of air pollution, according to a new study.

“Exposure to airborne particulate matter can lead to endothelial dysfunction, a condition in which the endothelium of blood vessels does not function normally, which is a risk factor for clinical cardiovascular events and progression of atherosclerosis,” said Haiyan Tong,

MD, PhD, of the US Environmental Protection Agency.

“As olive oil and fish oil are known to have beneficial effects on endothelial dysfunction, we examined whether use of these supplements would counteract the adverse cardiovascular effects of exposure to concentrated ambient particulate matter in a controlled setting.”

Dr Tong and his colleagues presented their findings at the American Thoracic Society’s 2014 International Conference (abstract 55100).

Their study involved 42 healthy adults who were randomized to receive 3 g/day of olive oil, fish oil, or no supplements for 4 weeks. Subjects then underwent controlled, 2-hour exposures to filtered air, followed on the next day by exposure to fine/ultrafine concentrated ambient particulate matter (CAP, mean mass concentration 253±16 µg/m³) in a controlled-exposure chamber.

The researchers assessed endothelial function by sonographic measurement of flow-mediated dilation of the brachial artery before, immediately after, and 20 hours after exposure to air and CAP. They also measured blood markers of vasoconstriction and fibrinolysis.

Immediately after exposure to CAP, there were significant particulate matter mass-dependent reductions in flow-mediated dilation in the control group (-19.4±8.4% per 100 µg/m³ increase in CAP concentration relative to pre-filtered air levels) and the fish oil group (-13.7±5.3%), but the decrease in the olive oil group was not significant (-7.6±6.8%).

Tissue plasminogen activator increased immediately after CAP exposure in the olive oil group (11.6±5%), and this effect persisted for up to 20 hours.

Olive oil supplementation also ameliorated changes in blood markers associated with vasoconstriction and fibrinolysis, while fish oil supplementation had no effect on endothelial function or fibrinolysis after CAP exposure.

“Our study suggests that use of olive oil supplements may protect against the adverse vascular effects of exposure to air pollution particles,” Dr Tong said. “If these results are replicated in further studies, use of these supplements might offer a safe, low-cost, and effective means of counteracting some of the health consequences of exposure to air pollution.”

Blood vessels

SAN DIEGO—Taking olive oil supplements may counteract some of the adverse cardiovascular effects of air pollution, according to a new study.

“Exposure to airborne particulate matter can lead to endothelial dysfunction, a condition in which the endothelium of blood vessels does not function normally, which is a risk factor for clinical cardiovascular events and progression of atherosclerosis,” said Haiyan Tong,

MD, PhD, of the US Environmental Protection Agency.

“As olive oil and fish oil are known to have beneficial effects on endothelial dysfunction, we examined whether use of these supplements would counteract the adverse cardiovascular effects of exposure to concentrated ambient particulate matter in a controlled setting.”

Dr Tong and his colleagues presented their findings at the American Thoracic Society’s 2014 International Conference (abstract 55100).

Their study involved 42 healthy adults who were randomized to receive 3 g/day of olive oil, fish oil, or no supplements for 4 weeks. Subjects then underwent controlled, 2-hour exposures to filtered air, followed on the next day by exposure to fine/ultrafine concentrated ambient particulate matter (CAP, mean mass concentration 253±16 µg/m³) in a controlled-exposure chamber.

The researchers assessed endothelial function by sonographic measurement of flow-mediated dilation of the brachial artery before, immediately after, and 20 hours after exposure to air and CAP. They also measured blood markers of vasoconstriction and fibrinolysis.

Immediately after exposure to CAP, there were significant particulate matter mass-dependent reductions in flow-mediated dilation in the control group (-19.4±8.4% per 100 µg/m³ increase in CAP concentration relative to pre-filtered air levels) and the fish oil group (-13.7±5.3%), but the decrease in the olive oil group was not significant (-7.6±6.8%).

Tissue plasminogen activator increased immediately after CAP exposure in the olive oil group (11.6±5%), and this effect persisted for up to 20 hours.

Olive oil supplementation also ameliorated changes in blood markers associated with vasoconstriction and fibrinolysis, while fish oil supplementation had no effect on endothelial function or fibrinolysis after CAP exposure.

“Our study suggests that use of olive oil supplements may protect against the adverse vascular effects of exposure to air pollution particles,” Dr Tong said. “If these results are replicated in further studies, use of these supplements might offer a safe, low-cost, and effective means of counteracting some of the health consequences of exposure to air pollution.”

Lab-on-a-chip device

Institute of Photonic Sciences

Scientists say they’ve developed a lab-on-a-chip device capable of detecting protein markers for cancer.

The device can detect very low concentrations of protein markers in the blood, enabling cancer diagnosis in its earliest stages, the team says.

Romain Quidant, PhD, of The Institute of Photonic Sciences in Barcelona, Spain, and his colleagues described the device in Nano Letters.

The lab on a chip hosts 32 sensing sites distributed across a network of 8 fluidic microchannels that enables it to conduct multiple analyses.

Gold nanoparticles lie on the surface of the chip and are chemically programed with an antibody receptor in such a way that they are capable of specifically attracting the protein markers circulating in blood.

When a drop of blood is injected into the chip, it circulates through the microchannels, and, if cancer markers are present in the blood, they will stick to the nanoparticles located on the microchannels as they pass by, setting off changes in what is known as the plasmonic resonance.

The device monitors these changes, the magnitude of which is directly related to the concentration/number of markers in the patient’s blood. In this way, it provides a direct assessment of the patient’s risk of developing cancer.

“The most fascinating finding is that we are capable of detecting extremely low concentrations of this protein in a matter of minutes, making this device an ultra-high-sensitivity, state-of-the-art, powerful instrument that will benefit early detection and treatment monitoring of cancer,” Dr Quidant said.

Lab-on-a-chip device

Institute of Photonic Sciences

Scientists say they’ve developed a lab-on-a-chip device capable of detecting protein markers for cancer.

The device can detect very low concentrations of protein markers in the blood, enabling cancer diagnosis in its earliest stages, the team says.

Romain Quidant, PhD, of The Institute of Photonic Sciences in Barcelona, Spain, and his colleagues described the device in Nano Letters.

The lab on a chip hosts 32 sensing sites distributed across a network of 8 fluidic microchannels that enables it to conduct multiple analyses.

Gold nanoparticles lie on the surface of the chip and are chemically programed with an antibody receptor in such a way that they are capable of specifically attracting the protein markers circulating in blood.

When a drop of blood is injected into the chip, it circulates through the microchannels, and, if cancer markers are present in the blood, they will stick to the nanoparticles located on the microchannels as they pass by, setting off changes in what is known as the plasmonic resonance.

The device monitors these changes, the magnitude of which is directly related to the concentration/number of markers in the patient’s blood. In this way, it provides a direct assessment of the patient’s risk of developing cancer.

“The most fascinating finding is that we are capable of detecting extremely low concentrations of this protein in a matter of minutes, making this device an ultra-high-sensitivity, state-of-the-art, powerful instrument that will benefit early detection and treatment monitoring of cancer,” Dr Quidant said.

Lab-on-a-chip device

Institute of Photonic Sciences

Scientists say they’ve developed a lab-on-a-chip device capable of detecting protein markers for cancer.

The device can detect very low concentrations of protein markers in the blood, enabling cancer diagnosis in its earliest stages, the team says.

Romain Quidant, PhD, of The Institute of Photonic Sciences in Barcelona, Spain, and his colleagues described the device in Nano Letters.

The lab on a chip hosts 32 sensing sites distributed across a network of 8 fluidic microchannels that enables it to conduct multiple analyses.

Gold nanoparticles lie on the surface of the chip and are chemically programed with an antibody receptor in such a way that they are capable of specifically attracting the protein markers circulating in blood.

When a drop of blood is injected into the chip, it circulates through the microchannels, and, if cancer markers are present in the blood, they will stick to the nanoparticles located on the microchannels as they pass by, setting off changes in what is known as the plasmonic resonance.

The device monitors these changes, the magnitude of which is directly related to the concentration/number of markers in the patient’s blood. In this way, it provides a direct assessment of the patient’s risk of developing cancer.

“The most fascinating finding is that we are capable of detecting extremely low concentrations of this protein in a matter of minutes, making this device an ultra-high-sensitivity, state-of-the-art, powerful instrument that will benefit early detection and treatment monitoring of cancer,” Dr Quidant said.

Doctor consults with cancer

patient and her father

Credit: Rhoda Baer

New research suggests a need to revisit cardiac screening guidelines for survivors of childhood cancers.

The study indicates that less frequent screening for early signs of impending congestive heart failure (CHF) may yield a similar clinical benefit as current screening recommendations.

Furthermore, some survivors might be better served by a different method of screening than the one currently used. And early treatment of patients at high risk of CHF may be beneficial.

The researchers reported these findings in the Annals of Internal Medicine.

Current CHF screening guidelines recommend that childhood cancer survivors treated with chemotherapeutic agents known to affect long-term heart health be screened as often as every year, with a schedule dependent on their level of CHF risk.

The Children’s Oncology Group (COG) recommends that survivors undergo screening by echocardiography for asymptomatic left ventricular dysfunction (ALVD). If left untreated, this clinically silent condition can progress to CHF, so clinicians typically prescribe beta blockers and ACE inhibitors to patients with signs of ALVD.

The COG recommends that patients at high risk of developing CHF be screened every year or 2 and those at low risk be screened every 2 or 5 years

“It is important to monitor survivors so we can reduce the late effects of treatment whenever possible, but we may be asking them to be tested too often, which burdens both individuals and the healthcare system,” said study author Lisa Diller, MD, of the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in Massachusetts. “We think it is worthwhile to review the current CHF screening guidelines.”

To estimate the clinical benefits and cost-effectiveness of the current heart screening guidelines, Dr Diller and her colleagues constructed a computer model of a virtual cohort of 15-year-olds who had survived cancer at least 5 years.

Using data from the Childhood Cancer Survivors Study and the Framingham Heart Study, the researchers modeled the cohort’s CHF risk and clinical progression over the course of survivors’ lifetimes. Results suggested that routine screening may prevent as many as 1 in 12 cases of CHF.

The team then used Medicare data to estimate the costs and value (expressed in cost per quality-adjusted life-year [QALY]) of different screening schedules—every 1, 2, 5, or 10 years—and methods—echocardiography vs cardiac magnetic resonance imaging (cMRI)—for the different CHF risk groups.

At a cost-effectiveness threshold of $100,000/QALY, the model’s results indicated that echocardiographic screening might not be the best value for resources invested to reduce lifetime CHF risk among survivors at low risk of developing the disease.

On the other hand, the data suggested that biennial echocardiography screening may be a high-value strategy for high-risk survivors.

The simulation’s data also suggested that cMRI may be preferable to echocardiography as a screening method, with cMRI’s greater cost per test balanced by its greater sensitivity. According to the model, cMRI-based screening of low-risk survivors every 10 years and high-risk survivors every 5 years was more cost-effective than any echocardiography-based schedule.

Lastly, the data suggested it may be most beneficial to treat high-risk survivors before signs of ALVD even appear. For instance, proactively treating all high-risk patients in the virtual cohort with ACE inhibitors and beta blockers reduced their lifetime CHF risk more than if they received an echocardiograph every 2 years.

The researchers relied on simulation modeling using the best available clinical and epidemiologic data because of the logistical obstacles to conducting a prospective, randomized, clinical trial.

They said enrolling the number of survivors needed for such a study would be challenging, given how rare childhood cancers are. Yet guidance on the health benefits associated with current recommendations is needed.

“Our findings suggest that there is a long-term benefit in screening survivors at elevated risk for CHF,” said study author Jennifer Yeh, PhD, of the Harvard School of Public Health in Boston.

“Yet less frequent screening than currently recommended may be reasonable when other factors are considered. We hope these results can help inform the ongoing discussion about screening childhood cancer survivors.”

Doctor consults with cancer

patient and her father

Credit: Rhoda Baer

New research suggests a need to revisit cardiac screening guidelines for survivors of childhood cancers.

The study indicates that less frequent screening for early signs of impending congestive heart failure (CHF) may yield a similar clinical benefit as current screening recommendations.

Furthermore, some survivors might be better served by a different method of screening than the one currently used. And early treatment of patients at high risk of CHF may be beneficial.

The researchers reported these findings in the Annals of Internal Medicine.

Current CHF screening guidelines recommend that childhood cancer survivors treated with chemotherapeutic agents known to affect long-term heart health be screened as often as every year, with a schedule dependent on their level of CHF risk.

The Children’s Oncology Group (COG) recommends that survivors undergo screening by echocardiography for asymptomatic left ventricular dysfunction (ALVD). If left untreated, this clinically silent condition can progress to CHF, so clinicians typically prescribe beta blockers and ACE inhibitors to patients with signs of ALVD.

The COG recommends that patients at high risk of developing CHF be screened every year or 2 and those at low risk be screened every 2 or 5 years

“It is important to monitor survivors so we can reduce the late effects of treatment whenever possible, but we may be asking them to be tested too often, which burdens both individuals and the healthcare system,” said study author Lisa Diller, MD, of the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in Massachusetts. “We think it is worthwhile to review the current CHF screening guidelines.”

To estimate the clinical benefits and cost-effectiveness of the current heart screening guidelines, Dr Diller and her colleagues constructed a computer model of a virtual cohort of 15-year-olds who had survived cancer at least 5 years.

Using data from the Childhood Cancer Survivors Study and the Framingham Heart Study, the researchers modeled the cohort’s CHF risk and clinical progression over the course of survivors’ lifetimes. Results suggested that routine screening may prevent as many as 1 in 12 cases of CHF.

The team then used Medicare data to estimate the costs and value (expressed in cost per quality-adjusted life-year [QALY]) of different screening schedules—every 1, 2, 5, or 10 years—and methods—echocardiography vs cardiac magnetic resonance imaging (cMRI)—for the different CHF risk groups.

At a cost-effectiveness threshold of $100,000/QALY, the model’s results indicated that echocardiographic screening might not be the best value for resources invested to reduce lifetime CHF risk among survivors at low risk of developing the disease.

On the other hand, the data suggested that biennial echocardiography screening may be a high-value strategy for high-risk survivors.

The simulation’s data also suggested that cMRI may be preferable to echocardiography as a screening method, with cMRI’s greater cost per test balanced by its greater sensitivity. According to the model, cMRI-based screening of low-risk survivors every 10 years and high-risk survivors every 5 years was more cost-effective than any echocardiography-based schedule.

Lastly, the data suggested it may be most beneficial to treat high-risk survivors before signs of ALVD even appear. For instance, proactively treating all high-risk patients in the virtual cohort with ACE inhibitors and beta blockers reduced their lifetime CHF risk more than if they received an echocardiograph every 2 years.

The researchers relied on simulation modeling using the best available clinical and epidemiologic data because of the logistical obstacles to conducting a prospective, randomized, clinical trial.

They said enrolling the number of survivors needed for such a study would be challenging, given how rare childhood cancers are. Yet guidance on the health benefits associated with current recommendations is needed.

“Our findings suggest that there is a long-term benefit in screening survivors at elevated risk for CHF,” said study author Jennifer Yeh, PhD, of the Harvard School of Public Health in Boston.

“Yet less frequent screening than currently recommended may be reasonable when other factors are considered. We hope these results can help inform the ongoing discussion about screening childhood cancer survivors.”

Doctor consults with cancer

patient and her father

Credit: Rhoda Baer

New research suggests a need to revisit cardiac screening guidelines for survivors of childhood cancers.

The study indicates that less frequent screening for early signs of impending congestive heart failure (CHF) may yield a similar clinical benefit as current screening recommendations.

Furthermore, some survivors might be better served by a different method of screening than the one currently used. And early treatment of patients at high risk of CHF may be beneficial.

The researchers reported these findings in the Annals of Internal Medicine.

Current CHF screening guidelines recommend that childhood cancer survivors treated with chemotherapeutic agents known to affect long-term heart health be screened as often as every year, with a schedule dependent on their level of CHF risk.

The Children’s Oncology Group (COG) recommends that survivors undergo screening by echocardiography for asymptomatic left ventricular dysfunction (ALVD). If left untreated, this clinically silent condition can progress to CHF, so clinicians typically prescribe beta blockers and ACE inhibitors to patients with signs of ALVD.

The COG recommends that patients at high risk of developing CHF be screened every year or 2 and those at low risk be screened every 2 or 5 years

“It is important to monitor survivors so we can reduce the late effects of treatment whenever possible, but we may be asking them to be tested too often, which burdens both individuals and the healthcare system,” said study author Lisa Diller, MD, of the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in Massachusetts. “We think it is worthwhile to review the current CHF screening guidelines.”

To estimate the clinical benefits and cost-effectiveness of the current heart screening guidelines, Dr Diller and her colleagues constructed a computer model of a virtual cohort of 15-year-olds who had survived cancer at least 5 years.

Using data from the Childhood Cancer Survivors Study and the Framingham Heart Study, the researchers modeled the cohort’s CHF risk and clinical progression over the course of survivors’ lifetimes. Results suggested that routine screening may prevent as many as 1 in 12 cases of CHF.

The team then used Medicare data to estimate the costs and value (expressed in cost per quality-adjusted life-year [QALY]) of different screening schedules—every 1, 2, 5, or 10 years—and methods—echocardiography vs cardiac magnetic resonance imaging (cMRI)—for the different CHF risk groups.

At a cost-effectiveness threshold of $100,000/QALY, the model’s results indicated that echocardiographic screening might not be the best value for resources invested to reduce lifetime CHF risk among survivors at low risk of developing the disease.

On the other hand, the data suggested that biennial echocardiography screening may be a high-value strategy for high-risk survivors.

The simulation’s data also suggested that cMRI may be preferable to echocardiography as a screening method, with cMRI’s greater cost per test balanced by its greater sensitivity. According to the model, cMRI-based screening of low-risk survivors every 10 years and high-risk survivors every 5 years was more cost-effective than any echocardiography-based schedule.

Lastly, the data suggested it may be most beneficial to treat high-risk survivors before signs of ALVD even appear. For instance, proactively treating all high-risk patients in the virtual cohort with ACE inhibitors and beta blockers reduced their lifetime CHF risk more than if they received an echocardiograph every 2 years.

The researchers relied on simulation modeling using the best available clinical and epidemiologic data because of the logistical obstacles to conducting a prospective, randomized, clinical trial.

They said enrolling the number of survivors needed for such a study would be challenging, given how rare childhood cancers are. Yet guidance on the health benefits associated with current recommendations is needed.

“Our findings suggest that there is a long-term benefit in screening survivors at elevated risk for CHF,” said study author Jennifer Yeh, PhD, of the Harvard School of Public Health in Boston.

“Yet less frequent screening than currently recommended may be reasonable when other factors are considered. We hope these results can help inform the ongoing discussion about screening childhood cancer survivors.”