Scientist at a computer

Credit: Darren Baker

A handful of newly identified compounds may be able to treat chronic myelogenous leukemia (CML) more effectively than the tyrosine kinase inhibitors (TKIs) currently on the market, new research suggests.

Investigators identified 7 molecules that exhibited the potential to be more potent than approved TKIs.

Experiments suggested that 5 of the compounds—DB07107, DB06977, ST013616, DB04200, and ST007180—were more effective at inhibiting T315I-mutant BCR-ABL than wild-type BCR-ABL.

And 2 of them—ST019342 and DB01172—were effective only against mutant BCR-ABL.

Hemanth Naick Banavath, a PhD student at Pondicherry University-India, and his colleagues detailed these results in Nature: Scientific Reports.

To identify compounds to treat CML, the investigators screened several small molecule databases and docked against wild-type and drug-resistant T315I-mutant BCR-ABL.

The team also docked the TKIs ponatinib, bosutinib, bafetinib, dasatinib, nilotinib, and imatinib.

They identified 7 lead molecules—DB07107, DB06977, ST013616, DB04200, ST007180, ST019342, and DB01172—with better binding affinity and higher binding free energy than the TKIs.

Molecular dynamics simulations showed the dynamic behavior of protein-ligand complexes.

The protein backbone and ligand backbone of DB07107, DB06977, ST013616, DB04200, ST007180, and DB01172 were stable throughout the simulation period.

But the backbone of ST019342 showed anomalous fluctuations, and DB01172 showed instability with wild-type BCR-ABL.

A hydrogen bond analysis revealed that DB01172 has 6 hydrogens on average. However, in wild-type, it has 2 to 3 hydrogens on average. The investigators said this suggests low efficacy toward wild-type BCR-ABL.

Taking these findings together, the team said they cannot recommend ST019342 and DB01172 as potential treatments for CML.

On the other hand, they can endorse DB07107, DB06977, ST013616, DB04200, and ST007180, which showed “remarkable results.”

Scientist at a computer

Credit: Darren Baker

A handful of newly identified compounds may be able to treat chronic myelogenous leukemia (CML) more effectively than the tyrosine kinase inhibitors (TKIs) currently on the market, new research suggests.

Investigators identified 7 molecules that exhibited the potential to be more potent than approved TKIs.

Experiments suggested that 5 of the compounds—DB07107, DB06977, ST013616, DB04200, and ST007180—were more effective at inhibiting T315I-mutant BCR-ABL than wild-type BCR-ABL.

And 2 of them—ST019342 and DB01172—were effective only against mutant BCR-ABL.

Hemanth Naick Banavath, a PhD student at Pondicherry University-India, and his colleagues detailed these results in Nature: Scientific Reports.

To identify compounds to treat CML, the investigators screened several small molecule databases and docked against wild-type and drug-resistant T315I-mutant BCR-ABL.

The team also docked the TKIs ponatinib, bosutinib, bafetinib, dasatinib, nilotinib, and imatinib.

They identified 7 lead molecules—DB07107, DB06977, ST013616, DB04200, ST007180, ST019342, and DB01172—with better binding affinity and higher binding free energy than the TKIs.

Molecular dynamics simulations showed the dynamic behavior of protein-ligand complexes.

The protein backbone and ligand backbone of DB07107, DB06977, ST013616, DB04200, ST007180, and DB01172 were stable throughout the simulation period.

But the backbone of ST019342 showed anomalous fluctuations, and DB01172 showed instability with wild-type BCR-ABL.

A hydrogen bond analysis revealed that DB01172 has 6 hydrogens on average. However, in wild-type, it has 2 to 3 hydrogens on average. The investigators said this suggests low efficacy toward wild-type BCR-ABL.

Taking these findings together, the team said they cannot recommend ST019342 and DB01172 as potential treatments for CML.

On the other hand, they can endorse DB07107, DB06977, ST013616, DB04200, and ST007180, which showed “remarkable results.”

Scientist at a computer

Credit: Darren Baker

A handful of newly identified compounds may be able to treat chronic myelogenous leukemia (CML) more effectively than the tyrosine kinase inhibitors (TKIs) currently on the market, new research suggests.

Investigators identified 7 molecules that exhibited the potential to be more potent than approved TKIs.

Experiments suggested that 5 of the compounds—DB07107, DB06977, ST013616, DB04200, and ST007180—were more effective at inhibiting T315I-mutant BCR-ABL than wild-type BCR-ABL.

And 2 of them—ST019342 and DB01172—were effective only against mutant BCR-ABL.

Hemanth Naick Banavath, a PhD student at Pondicherry University-India, and his colleagues detailed these results in Nature: Scientific Reports.

To identify compounds to treat CML, the investigators screened several small molecule databases and docked against wild-type and drug-resistant T315I-mutant BCR-ABL.

The team also docked the TKIs ponatinib, bosutinib, bafetinib, dasatinib, nilotinib, and imatinib.

They identified 7 lead molecules—DB07107, DB06977, ST013616, DB04200, ST007180, ST019342, and DB01172—with better binding affinity and higher binding free energy than the TKIs.

Molecular dynamics simulations showed the dynamic behavior of protein-ligand complexes.

The protein backbone and ligand backbone of DB07107, DB06977, ST013616, DB04200, ST007180, and DB01172 were stable throughout the simulation period.

But the backbone of ST019342 showed anomalous fluctuations, and DB01172 showed instability with wild-type BCR-ABL.

A hydrogen bond analysis revealed that DB01172 has 6 hydrogens on average. However, in wild-type, it has 2 to 3 hydrogens on average. The investigators said this suggests low efficacy toward wild-type BCR-ABL.

Taking these findings together, the team said they cannot recommend ST019342 and DB01172 as potential treatments for CML.

On the other hand, they can endorse DB07107, DB06977, ST013616, DB04200, and ST007180, which showed “remarkable results.”

Doctor consults with cancer

patient and her father

Credit: Rhoda Baer

A new tool can identify patients with limited cancer health literacy, according to research published in the Journal of Health Communications.

The study authors noted that cancer patients are expected to play an active role in their care by adhering to medication regimens, distinguishing between scientifically credible medical evidence and misconceptions, and communicating with their providers about treatment decisions, risks, and survival rates.

However, patients with limited cancer health literacy can struggle with these responsibilities and potentially jeopardize their health by making uninformed decisions.

So Levent Dumenci, PhD, of Virginia Commonwealth University in Richmond, and his colleagues developed a tool to assess health literacy among cancer patients.

“Before now, there were only instruments that measured a particular aspect of general health literacy,” Dr Dumenci said. “It is important to have a tool that is specific to cancer because of the complex treatment options that cancer patients face, along with the increased demand for self-care.”

To meet that need, he and his colleagues developed the Cancer Health Literacy Test (CHLT)-30. The test, which is given via a touch-screen device, includes 30

questions about cancer treatment, medication side effects, and other cancer-related issues.

Six of the questions (CHLT-6) were specifically designed to quickly identify individuals with limited cancer health literacy.

The researchers tested the CHLT-30 in 1306 African American and Caucasian patients who were treated at oncology clinics in Virginia.

The team said the test accurately measured literacy and quickly identified patients with limited cancer health literacy. Eighteen percent of cancer patients had limited literacy, with an overrepresentation of African American, undereducated, and low-income patients.

“Using this tool, it takes just 1 to 2 minutes in the doctor’s office waiting room to identify patients with limited [cancer health literacy],” Dr Dumenci said. “Then, this information can be digitally communicated to the doctors prior to seeing the patients, so that they are prepared to talk with the patients in terms they can understand. This simple change could lead to big improvements in health outcomes.”

In future studies, the researchers hope to evaluate the cancer health literacy of Hispanic patients because prior research has pointed to disparities in this population’s health literacy.

Doctor consults with cancer

patient and her father

Credit: Rhoda Baer

A new tool can identify patients with limited cancer health literacy, according to research published in the Journal of Health Communications.

The study authors noted that cancer patients are expected to play an active role in their care by adhering to medication regimens, distinguishing between scientifically credible medical evidence and misconceptions, and communicating with their providers about treatment decisions, risks, and survival rates.

However, patients with limited cancer health literacy can struggle with these responsibilities and potentially jeopardize their health by making uninformed decisions.

So Levent Dumenci, PhD, of Virginia Commonwealth University in Richmond, and his colleagues developed a tool to assess health literacy among cancer patients.

“Before now, there were only instruments that measured a particular aspect of general health literacy,” Dr Dumenci said. “It is important to have a tool that is specific to cancer because of the complex treatment options that cancer patients face, along with the increased demand for self-care.”

To meet that need, he and his colleagues developed the Cancer Health Literacy Test (CHLT)-30. The test, which is given via a touch-screen device, includes 30

questions about cancer treatment, medication side effects, and other cancer-related issues.

Six of the questions (CHLT-6) were specifically designed to quickly identify individuals with limited cancer health literacy.

The researchers tested the CHLT-30 in 1306 African American and Caucasian patients who were treated at oncology clinics in Virginia.

The team said the test accurately measured literacy and quickly identified patients with limited cancer health literacy. Eighteen percent of cancer patients had limited literacy, with an overrepresentation of African American, undereducated, and low-income patients.

“Using this tool, it takes just 1 to 2 minutes in the doctor’s office waiting room to identify patients with limited [cancer health literacy],” Dr Dumenci said. “Then, this information can be digitally communicated to the doctors prior to seeing the patients, so that they are prepared to talk with the patients in terms they can understand. This simple change could lead to big improvements in health outcomes.”

In future studies, the researchers hope to evaluate the cancer health literacy of Hispanic patients because prior research has pointed to disparities in this population’s health literacy.

Doctor consults with cancer

patient and her father

Credit: Rhoda Baer

A new tool can identify patients with limited cancer health literacy, according to research published in the Journal of Health Communications.

The study authors noted that cancer patients are expected to play an active role in their care by adhering to medication regimens, distinguishing between scientifically credible medical evidence and misconceptions, and communicating with their providers about treatment decisions, risks, and survival rates.

However, patients with limited cancer health literacy can struggle with these responsibilities and potentially jeopardize their health by making uninformed decisions.

So Levent Dumenci, PhD, of Virginia Commonwealth University in Richmond, and his colleagues developed a tool to assess health literacy among cancer patients.

“Before now, there were only instruments that measured a particular aspect of general health literacy,” Dr Dumenci said. “It is important to have a tool that is specific to cancer because of the complex treatment options that cancer patients face, along with the increased demand for self-care.”

To meet that need, he and his colleagues developed the Cancer Health Literacy Test (CHLT)-30. The test, which is given via a touch-screen device, includes 30

questions about cancer treatment, medication side effects, and other cancer-related issues.

Six of the questions (CHLT-6) were specifically designed to quickly identify individuals with limited cancer health literacy.

The researchers tested the CHLT-30 in 1306 African American and Caucasian patients who were treated at oncology clinics in Virginia.

The team said the test accurately measured literacy and quickly identified patients with limited cancer health literacy. Eighteen percent of cancer patients had limited literacy, with an overrepresentation of African American, undereducated, and low-income patients.

“Using this tool, it takes just 1 to 2 minutes in the doctor’s office waiting room to identify patients with limited [cancer health literacy],” Dr Dumenci said. “Then, this information can be digitally communicated to the doctors prior to seeing the patients, so that they are prepared to talk with the patients in terms they can understand. This simple change could lead to big improvements in health outcomes.”

In future studies, the researchers hope to evaluate the cancer health literacy of Hispanic patients because prior research has pointed to disparities in this population’s health literacy.

Platelets for transfusion

The AABB has developed new guidelines that specify situations

in which adults should receive platelet transfusions.

The group’s

recommendations are based on results of a systematic review.

The

suggestions cover several clinical situations in which platelet

transfusions might be an option, such as therapy-induced hypoproliferative thrombocytopenia, central venous catheter placement, diagnostic lumbar puncture, and cardiac surgery.

To formulate the guidelines, researchers conducted a review of randomized clinical trials and observational studies published from 1900 through September 2014. All studies reported clinical outcomes in patients receiving prophylactic or therapeutic platelet transfusions.

Based on the collected data, the AABB now strongly recommends prophylactic platelet transfusions to reduce the risk for spontaneous bleeding in hospitalized adults with therapy-induced hypoproliferative thrombocytopenia and a platelet count of 10 x 10⁹ cells/L or less. The recommendation states that transfusing 0.5 to 1 apheresis unit is sufficient in these patients.

A weaker recommendation is that prophylactic platelet transfusions be given to patients undergoing elective central venous catheter placement who have a platelet count of less than 20 x 10⁹ cells/L.

Likewise, the AABB says prophylactic transfusions should be given to patients having elective diagnostic lumbar puncture or major elective nonneuraxial surgery who have a platelet count less than 50 x 10⁹ cells/L.

Another weak recommendation advises against routine prophylactic platelet transfusions in patients who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass.

The AABB also suggests (without recommending) that patients with perioperative bleeding and thrombocytopenia or platelet dysfunction may benefit from transfusions.

Finally, the AABB said it cannot recommend for or against platelet transfusions in patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous).

For more details, see the complete guidelines in Annals of Internal Medicine.

Platelets for transfusion

The AABB has developed new guidelines that specify situations

in which adults should receive platelet transfusions.

The group’s

recommendations are based on results of a systematic review.

The

suggestions cover several clinical situations in which platelet

transfusions might be an option, such as therapy-induced hypoproliferative thrombocytopenia, central venous catheter placement, diagnostic lumbar puncture, and cardiac surgery.

To formulate the guidelines, researchers conducted a review of randomized clinical trials and observational studies published from 1900 through September 2014. All studies reported clinical outcomes in patients receiving prophylactic or therapeutic platelet transfusions.

Based on the collected data, the AABB now strongly recommends prophylactic platelet transfusions to reduce the risk for spontaneous bleeding in hospitalized adults with therapy-induced hypoproliferative thrombocytopenia and a platelet count of 10 x 10⁹ cells/L or less. The recommendation states that transfusing 0.5 to 1 apheresis unit is sufficient in these patients.

A weaker recommendation is that prophylactic platelet transfusions be given to patients undergoing elective central venous catheter placement who have a platelet count of less than 20 x 10⁹ cells/L.

Likewise, the AABB says prophylactic transfusions should be given to patients having elective diagnostic lumbar puncture or major elective nonneuraxial surgery who have a platelet count less than 50 x 10⁹ cells/L.

Another weak recommendation advises against routine prophylactic platelet transfusions in patients who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass.

The AABB also suggests (without recommending) that patients with perioperative bleeding and thrombocytopenia or platelet dysfunction may benefit from transfusions.

Finally, the AABB said it cannot recommend for or against platelet transfusions in patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous).

For more details, see the complete guidelines in Annals of Internal Medicine.

Platelets for transfusion

The AABB has developed new guidelines that specify situations

in which adults should receive platelet transfusions.

The group’s

recommendations are based on results of a systematic review.

The

suggestions cover several clinical situations in which platelet

transfusions might be an option, such as therapy-induced hypoproliferative thrombocytopenia, central venous catheter placement, diagnostic lumbar puncture, and cardiac surgery.

To formulate the guidelines, researchers conducted a review of randomized clinical trials and observational studies published from 1900 through September 2014. All studies reported clinical outcomes in patients receiving prophylactic or therapeutic platelet transfusions.

Based on the collected data, the AABB now strongly recommends prophylactic platelet transfusions to reduce the risk for spontaneous bleeding in hospitalized adults with therapy-induced hypoproliferative thrombocytopenia and a platelet count of 10 x 10⁹ cells/L or less. The recommendation states that transfusing 0.5 to 1 apheresis unit is sufficient in these patients.

A weaker recommendation is that prophylactic platelet transfusions be given to patients undergoing elective central venous catheter placement who have a platelet count of less than 20 x 10⁹ cells/L.

Likewise, the AABB says prophylactic transfusions should be given to patients having elective diagnostic lumbar puncture or major elective nonneuraxial surgery who have a platelet count less than 50 x 10⁹ cells/L.

Another weak recommendation advises against routine prophylactic platelet transfusions in patients who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass.

The AABB also suggests (without recommending) that patients with perioperative bleeding and thrombocytopenia or platelet dysfunction may benefit from transfusions.

Finally, the AABB said it cannot recommend for or against platelet transfusions in patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous).

For more details, see the complete guidelines in Annals of Internal Medicine.

PHILADELPHIA—The demand for blood transfusions increases substantially during high malaria transmission season, according to a study of hospitals in Tanzania.

On average, blood demand increased about 24% from low transmission season to high transmission season.

And some hospitals could not meet the increased demand. Unmet demand was highest in government hospitals, followed by faith-based institutions and private facilities.

Bakary Drammeh, DrPH, of the Centers for Disease Control and Prevention in Atlanta, Georgia, and his colleagues presented these results in a poster (SP356) at the AABB Annual Meeting 2014.

The researchers analyzed 14,706 blood prescriptions at 42 Tanzanian hospitals—21 government, 9 private, and 12 faith-based institutions.

The team assessed the number of blood prescriptions according to high and low malaria transmission periods—June-July vs August-September.

On average, there were 130 monthly blood prescriptions written per 100 beds during high malaria transmission season and 107 written during low transmission season.

There were 189 and 153 units of blood or blood components requested per 100 beds during high and low seasons, respectively. And there were 159 and 127 units issued, respectively.

Ultimately, an average of 145 units were transfused per 100 beds during high malaria transmission season, and 122 were transfused during low transmission season.

Across all 42 hospitals, total blood prescriptions increased 29% from low malaria transmission season to high transmission season.

The number of units requested increased 26%, the number of units issued increased 34%, and the number of units transfused increased 28%.

So, on average, blood demand increased 23.5% at these 42 hospitals during high malaria transmission season. And some hospitals did not have enough blood to meet demand.

The unmet blood demand was highest in government hospitals, at 25%, compared to faith-based hospitals, at 11%, and private hospitals, at 5%.

The researchers said these results suggest blood services should monitor malaria transmission surveillance reports and revise or project blood collection targets to meet the anticipated demand.

PHILADELPHIA—The demand for blood transfusions increases substantially during high malaria transmission season, according to a study of hospitals in Tanzania.

On average, blood demand increased about 24% from low transmission season to high transmission season.

And some hospitals could not meet the increased demand. Unmet demand was highest in government hospitals, followed by faith-based institutions and private facilities.

Bakary Drammeh, DrPH, of the Centers for Disease Control and Prevention in Atlanta, Georgia, and his colleagues presented these results in a poster (SP356) at the AABB Annual Meeting 2014.

The researchers analyzed 14,706 blood prescriptions at 42 Tanzanian hospitals—21 government, 9 private, and 12 faith-based institutions.

The team assessed the number of blood prescriptions according to high and low malaria transmission periods—June-July vs August-September.

On average, there were 130 monthly blood prescriptions written per 100 beds during high malaria transmission season and 107 written during low transmission season.

There were 189 and 153 units of blood or blood components requested per 100 beds during high and low seasons, respectively. And there were 159 and 127 units issued, respectively.

Ultimately, an average of 145 units were transfused per 100 beds during high malaria transmission season, and 122 were transfused during low transmission season.

Across all 42 hospitals, total blood prescriptions increased 29% from low malaria transmission season to high transmission season.

The number of units requested increased 26%, the number of units issued increased 34%, and the number of units transfused increased 28%.

So, on average, blood demand increased 23.5% at these 42 hospitals during high malaria transmission season. And some hospitals did not have enough blood to meet demand.

The unmet blood demand was highest in government hospitals, at 25%, compared to faith-based hospitals, at 11%, and private hospitals, at 5%.

The researchers said these results suggest blood services should monitor malaria transmission surveillance reports and revise or project blood collection targets to meet the anticipated demand.

PHILADELPHIA—The demand for blood transfusions increases substantially during high malaria transmission season, according to a study of hospitals in Tanzania.

On average, blood demand increased about 24% from low transmission season to high transmission season.

And some hospitals could not meet the increased demand. Unmet demand was highest in government hospitals, followed by faith-based institutions and private facilities.

Bakary Drammeh, DrPH, of the Centers for Disease Control and Prevention in Atlanta, Georgia, and his colleagues presented these results in a poster (SP356) at the AABB Annual Meeting 2014.

The researchers analyzed 14,706 blood prescriptions at 42 Tanzanian hospitals—21 government, 9 private, and 12 faith-based institutions.

The team assessed the number of blood prescriptions according to high and low malaria transmission periods—June-July vs August-September.

On average, there were 130 monthly blood prescriptions written per 100 beds during high malaria transmission season and 107 written during low transmission season.

There were 189 and 153 units of blood or blood components requested per 100 beds during high and low seasons, respectively. And there were 159 and 127 units issued, respectively.

Ultimately, an average of 145 units were transfused per 100 beds during high malaria transmission season, and 122 were transfused during low transmission season.

Across all 42 hospitals, total blood prescriptions increased 29% from low malaria transmission season to high transmission season.

The number of units requested increased 26%, the number of units issued increased 34%, and the number of units transfused increased 28%.

So, on average, blood demand increased 23.5% at these 42 hospitals during high malaria transmission season. And some hospitals did not have enough blood to meet demand.

The unmet blood demand was highest in government hospitals, at 25%, compared to faith-based hospitals, at 11%, and private hospitals, at 5%.

The researchers said these results suggest blood services should monitor malaria transmission surveillance reports and revise or project blood collection targets to meet the anticipated demand.

Clinical question

For patients undergoing any inpatient surgery, is the presence of new-onset perioperative atrial fibrillation associated with a greater long-term risk of ischemic stroke?

Bottom line

Perioperative atrial fibrillation (AF) is associated with an increased risk of ischemic stroke for patients who are hospitalized for surgery. (LOE = 2b)

Reference

Gialdini G, Nearing K, Bhave PD, et al. Perioperative atrial fibrillation and the long-term risk of ischemic stroke. JAMA 2014;312:616-622.

Study design

Cohort (retrospective)

Funding source

Government

Setting

Inpatient (any location)

Synopsis

New-onset perioperative AF is very common but its long-term association with ischemic stroke is unknown. Using administrative data, these investigators identified all adult patients who underwent inpatient surgery during a 4-year period. Patients with preexisiting AF and those with documented cerebrovascular disease were excluded. More than 1.7 million patients were included in the study, with a mean follow-up of 2 years.

Overall, perioperative AF was found in 1.4% of this population, more frequently following cardiac surgery than any other type of surgery (16% vs 0.78%; P < .001). Patients who experienced perioperative AF were also more likely to have high vascular comorbidities, such as hypertension, diabetes, and coronary artery disease. The incidence of ischemic stroke after discharge in the overall cohort was 0.81%.

After adjusting for potential confounders, including age, sex, race, and cardiovascular comorbidities, perioperative AF was independently associated with ischemic stroke both following noncardiac surgery (hazard ratio [HR] 2.0, 95% CI 1.7 - 2.3) and cardiac surgery (HR 1.3, 95% CI 1.1 - 1.6). A further analysis using a specific diagnostic code for cardioembolic stroke showed an even greater association between perioperative AF and this subset of stroke (noncardiac surgery: HR 4.9, 95% CI 3.5 - 6.7; cardiac surgery: HR 2.1, 95% CI 1.4 - 3.1).

Of note, sicker patients in this study may have had more intense cardiac monitoring following their surgeries, leading to an ascertainment bias that could overestimate the association between perioperative AF and stroke. However, a sensitivity analysis using a comorbidity index did not change the findings of the primary analysis.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

For patients undergoing any inpatient surgery, is the presence of new-onset perioperative atrial fibrillation associated with a greater long-term risk of ischemic stroke?

Bottom line

Perioperative atrial fibrillation (AF) is associated with an increased risk of ischemic stroke for patients who are hospitalized for surgery. (LOE = 2b)

Reference

Gialdini G, Nearing K, Bhave PD, et al. Perioperative atrial fibrillation and the long-term risk of ischemic stroke. JAMA 2014;312:616-622.

Study design

Cohort (retrospective)

Funding source

Government

Setting

Inpatient (any location)

Synopsis

New-onset perioperative AF is very common but its long-term association with ischemic stroke is unknown. Using administrative data, these investigators identified all adult patients who underwent inpatient surgery during a 4-year period. Patients with preexisiting AF and those with documented cerebrovascular disease were excluded. More than 1.7 million patients were included in the study, with a mean follow-up of 2 years.

Overall, perioperative AF was found in 1.4% of this population, more frequently following cardiac surgery than any other type of surgery (16% vs 0.78%; P < .001). Patients who experienced perioperative AF were also more likely to have high vascular comorbidities, such as hypertension, diabetes, and coronary artery disease. The incidence of ischemic stroke after discharge in the overall cohort was 0.81%.

After adjusting for potential confounders, including age, sex, race, and cardiovascular comorbidities, perioperative AF was independently associated with ischemic stroke both following noncardiac surgery (hazard ratio [HR] 2.0, 95% CI 1.7 - 2.3) and cardiac surgery (HR 1.3, 95% CI 1.1 - 1.6). A further analysis using a specific diagnostic code for cardioembolic stroke showed an even greater association between perioperative AF and this subset of stroke (noncardiac surgery: HR 4.9, 95% CI 3.5 - 6.7; cardiac surgery: HR 2.1, 95% CI 1.4 - 3.1).

Of note, sicker patients in this study may have had more intense cardiac monitoring following their surgeries, leading to an ascertainment bias that could overestimate the association between perioperative AF and stroke. However, a sensitivity analysis using a comorbidity index did not change the findings of the primary analysis.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

For patients undergoing any inpatient surgery, is the presence of new-onset perioperative atrial fibrillation associated with a greater long-term risk of ischemic stroke?

Bottom line

Perioperative atrial fibrillation (AF) is associated with an increased risk of ischemic stroke for patients who are hospitalized for surgery. (LOE = 2b)

Reference

Gialdini G, Nearing K, Bhave PD, et al. Perioperative atrial fibrillation and the long-term risk of ischemic stroke. JAMA 2014;312:616-622.

Study design

Cohort (retrospective)

Funding source

Government

Setting

Inpatient (any location)

Synopsis

New-onset perioperative AF is very common but its long-term association with ischemic stroke is unknown. Using administrative data, these investigators identified all adult patients who underwent inpatient surgery during a 4-year period. Patients with preexisiting AF and those with documented cerebrovascular disease were excluded. More than 1.7 million patients were included in the study, with a mean follow-up of 2 years.

Overall, perioperative AF was found in 1.4% of this population, more frequently following cardiac surgery than any other type of surgery (16% vs 0.78%; P < .001). Patients who experienced perioperative AF were also more likely to have high vascular comorbidities, such as hypertension, diabetes, and coronary artery disease. The incidence of ischemic stroke after discharge in the overall cohort was 0.81%.

After adjusting for potential confounders, including age, sex, race, and cardiovascular comorbidities, perioperative AF was independently associated with ischemic stroke both following noncardiac surgery (hazard ratio [HR] 2.0, 95% CI 1.7 - 2.3) and cardiac surgery (HR 1.3, 95% CI 1.1 - 1.6). A further analysis using a specific diagnostic code for cardioembolic stroke showed an even greater association between perioperative AF and this subset of stroke (noncardiac surgery: HR 4.9, 95% CI 3.5 - 6.7; cardiac surgery: HR 2.1, 95% CI 1.4 - 3.1).

Of note, sicker patients in this study may have had more intense cardiac monitoring following their surgeries, leading to an ascertainment bias that could overestimate the association between perioperative AF and stroke. However, a sensitivity analysis using a comorbidity index did not change the findings of the primary analysis.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does perioperative colchicine reduce postpericardiotomy syndrome following cardiac surgery?

Bottom line

The use of colchicine in the perioperative period decreases the incidence of postpericardiotomy syndrome after cardiac surgery with a number needed to treat (NNT) of 10. However, colchicine leads to adverse effects—specifically, gastrointestinal intolerance—and may not be tolerated during the vulnerable postoperative period. Findings in this study also suggest a role for colchicine in the prevention of postoperative atrial fibrillation, but this was not a primary outcome of this study and requires further investigation. (LOE = 1b)

Reference

Imazio M, Brucato A, Ferrazzi P, et al, for the COPPS-2 Investigators. Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation. JAMA 2014;312(10):1016-1023.

Study design

Randomized controlled trial (double-blinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Postpericardiotomy syndrome is a common complication after cardiac surgery and is defined by the presence of 2 of the following 5 criteria: fever without another cause, pleuritic chest pain, friction rub, new or worsening pericardial effusion, or pleural effusion with elevation in C-reactive protein levels.

To test the theory that perioperative colchicine can prevent postpericardiotomy syndrome, these investigators randomized 360 patients undergoing cardiac surgery to receive either colchicine at 0.5 mg twice daily (once daily for those who weighed less than 70 kg) or matching placebo. The study medication was started at 48 hours to 72 hours prior to surgery and continued for 1 month following surgery. Baseline characteristics of the 2 groups were similar, with two thirds of the patients undergoing either heart valve surgery or coronary artery bypass graft surgery.

The primary analysis was by intention to treat, but a prespecified on-treatment analysis was also performed. The overall study drug discontinuation rate for this trial was high (20%). Postpericardiotomy syndrome occurred less frequently in the colchicine group than in the placebo group at 3-month follow-up (19% vs 29%; absolute difference 10%; NNT = 10).

Additionally, although no significant difference was detected in the primary analysis, the on-treatment analysis did show a decrease in postoperative atrial fibrillation in the colchicine group (27% vs 41%; absolute difference 14%; NNT = 7). Adverse events were significantly greater in the colchicine group (20% vs 12%; number needed to treat to harm = 12), mainly due to increased gastrointestinal intolerance, but there was no difference between the 2 groups in the rate of study drug discontinuation.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does perioperative colchicine reduce postpericardiotomy syndrome following cardiac surgery?

Bottom line

The use of colchicine in the perioperative period decreases the incidence of postpericardiotomy syndrome after cardiac surgery with a number needed to treat (NNT) of 10. However, colchicine leads to adverse effects—specifically, gastrointestinal intolerance—and may not be tolerated during the vulnerable postoperative period. Findings in this study also suggest a role for colchicine in the prevention of postoperative atrial fibrillation, but this was not a primary outcome of this study and requires further investigation. (LOE = 1b)

Reference

Imazio M, Brucato A, Ferrazzi P, et al, for the COPPS-2 Investigators. Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation. JAMA 2014;312(10):1016-1023.

Study design

Randomized controlled trial (double-blinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Postpericardiotomy syndrome is a common complication after cardiac surgery and is defined by the presence of 2 of the following 5 criteria: fever without another cause, pleuritic chest pain, friction rub, new or worsening pericardial effusion, or pleural effusion with elevation in C-reactive protein levels.

To test the theory that perioperative colchicine can prevent postpericardiotomy syndrome, these investigators randomized 360 patients undergoing cardiac surgery to receive either colchicine at 0.5 mg twice daily (once daily for those who weighed less than 70 kg) or matching placebo. The study medication was started at 48 hours to 72 hours prior to surgery and continued for 1 month following surgery. Baseline characteristics of the 2 groups were similar, with two thirds of the patients undergoing either heart valve surgery or coronary artery bypass graft surgery.

The primary analysis was by intention to treat, but a prespecified on-treatment analysis was also performed. The overall study drug discontinuation rate for this trial was high (20%). Postpericardiotomy syndrome occurred less frequently in the colchicine group than in the placebo group at 3-month follow-up (19% vs 29%; absolute difference 10%; NNT = 10).

Additionally, although no significant difference was detected in the primary analysis, the on-treatment analysis did show a decrease in postoperative atrial fibrillation in the colchicine group (27% vs 41%; absolute difference 14%; NNT = 7). Adverse events were significantly greater in the colchicine group (20% vs 12%; number needed to treat to harm = 12), mainly due to increased gastrointestinal intolerance, but there was no difference between the 2 groups in the rate of study drug discontinuation.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does perioperative colchicine reduce postpericardiotomy syndrome following cardiac surgery?

Bottom line

The use of colchicine in the perioperative period decreases the incidence of postpericardiotomy syndrome after cardiac surgery with a number needed to treat (NNT) of 10. However, colchicine leads to adverse effects—specifically, gastrointestinal intolerance—and may not be tolerated during the vulnerable postoperative period. Findings in this study also suggest a role for colchicine in the prevention of postoperative atrial fibrillation, but this was not a primary outcome of this study and requires further investigation. (LOE = 1b)

Reference

Imazio M, Brucato A, Ferrazzi P, et al, for the COPPS-2 Investigators. Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation. JAMA 2014;312(10):1016-1023.

Study design

Randomized controlled trial (double-blinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Postpericardiotomy syndrome is a common complication after cardiac surgery and is defined by the presence of 2 of the following 5 criteria: fever without another cause, pleuritic chest pain, friction rub, new or worsening pericardial effusion, or pleural effusion with elevation in C-reactive protein levels.

To test the theory that perioperative colchicine can prevent postpericardiotomy syndrome, these investigators randomized 360 patients undergoing cardiac surgery to receive either colchicine at 0.5 mg twice daily (once daily for those who weighed less than 70 kg) or matching placebo. The study medication was started at 48 hours to 72 hours prior to surgery and continued for 1 month following surgery. Baseline characteristics of the 2 groups were similar, with two thirds of the patients undergoing either heart valve surgery or coronary artery bypass graft surgery.

The primary analysis was by intention to treat, but a prespecified on-treatment analysis was also performed. The overall study drug discontinuation rate for this trial was high (20%). Postpericardiotomy syndrome occurred less frequently in the colchicine group than in the placebo group at 3-month follow-up (19% vs 29%; absolute difference 10%; NNT = 10).

Additionally, although no significant difference was detected in the primary analysis, the on-treatment analysis did show a decrease in postoperative atrial fibrillation in the colchicine group (27% vs 41%; absolute difference 14%; NNT = 7). Adverse events were significantly greater in the colchicine group (20% vs 12%; number needed to treat to harm = 12), mainly due to increased gastrointestinal intolerance, but there was no difference between the 2 groups in the rate of study drug discontinuation.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

SAN FRANCISCO – To reduce unnecessary transfusions, all it takes is a reminder in the electronic medical record system that they aren’t generally necessary if surgery patients have hemoglobins greater than 10 g/dL, according to investigators from Emory University in Atlanta.

A reminder in Emory’s EMR dropped transfusion rates in cardiothoracic patients without increasing negative outcomes. It also saved money and reduced the number of surgical site infections. Emory is now rolling it out systemwide (J. Am. Coll. Surg. 2014 June 25 [doi: 10.1016/j.jamcollsurg.2014.06.012]). Lead investigator Dr. Seyed Razavi explained the initiative in a video interview at the annual clinical congress of the American College of Surgeons.

[email protected]

SAN FRANCISCO – To reduce unnecessary transfusions, all it takes is a reminder in the electronic medical record system that they aren’t generally necessary if surgery patients have hemoglobins greater than 10 g/dL, according to investigators from Emory University in Atlanta.

A reminder in Emory’s EMR dropped transfusion rates in cardiothoracic patients without increasing negative outcomes. It also saved money and reduced the number of surgical site infections. Emory is now rolling it out systemwide (J. Am. Coll. Surg. 2014 June 25 [doi: 10.1016/j.jamcollsurg.2014.06.012]). Lead investigator Dr. Seyed Razavi explained the initiative in a video interview at the annual clinical congress of the American College of Surgeons.

[email protected]

SAN FRANCISCO – To reduce unnecessary transfusions, all it takes is a reminder in the electronic medical record system that they aren’t generally necessary if surgery patients have hemoglobins greater than 10 g/dL, according to investigators from Emory University in Atlanta.

A reminder in Emory’s EMR dropped transfusion rates in cardiothoracic patients without increasing negative outcomes. It also saved money and reduced the number of surgical site infections. Emory is now rolling it out systemwide (J. Am. Coll. Surg. 2014 June 25 [doi: 10.1016/j.jamcollsurg.2014.06.012]). Lead investigator Dr. Seyed Razavi explained the initiative in a video interview at the annual clinical congress of the American College of Surgeons.

[email protected]

Pedunculagin is an ellagitannin, a group of polyphenolic hydrolyzable tannins, found in various plants, including Emblica officinalis, Pimenta dioica, and several others (Arch. Pharm. Res. 2014, Feb 7. [Epub ahead of print]; Curr. Drug Targets 2012;13:1900-06). The substance is reported to exhibit anti-inflammatory, anticancer, and antimicrobial activities, and it is considered a potent dietary antioxidant (Z. Naturforsch C. 2007;62:526-36; J. Org. Chem. 1996;61:2606-12; J. Nutr. 2014;144(4 Suppl):555S-60S). Purified from the Manchurian alder (Alnus hirsuta), pedunculagin is also a novel immunomodulating agent (Skin Res. Technol. 2010;16:371-7). Pedunculagin is also one of the hydrolyzable tannins found in Punica granatum (pomegranate), fruit extracts of which have been shown by Afaq et al. to exert photochemopreventive effects against the deleterious effects of ultraviolet B radiation (Photochem. Photobiol. 2005;81:38-45). Pedunculagin was first synthesized (in 2,3- and 4,6-coupled form) in 1996 (J. Org. Chem. 1996;61:2606-12).

Anticancer and antioxidant activity

In a study of 57 tannins and related compounds, Kashiwada et al. noted in a 1992 study that pedunculagin exhibited selective cytotoxicity against melanoma cells (J. Nat. Prod. 1992;55:1033-43).

According to a 2007 report by Marzouk et al., pedunculagin is among one of several tannins identified in the leaves of Pimenta dioica, and it is among the most potent free radical scavengers, as well as one of the most cytotoxic substances against solid tumor cancer cells. Pedunculagin also was found to significantly suppress nitric oxide production and spur the proliferation of T-lymphocytes and macrophages (Z. Naturforsch C. 2007;62:526-36).

In 2012, Kähkönen et al. observed that red raspberry and cloudberry ellagitannins, including pedunculagin, acted as effective radical scavengers, substantially contributing to the antioxidant activity of the berries in lipoprotein and lipid emulsion environments (J. Agric. Food Chem. 2012;60:1167-74).

A 2014 review by Hardman summarized several studies suggesting that potent anticancer properties, including antiproliferative and antiangiogenic activities, have been linked to walnuts. She noted that pedunculagin is one of the key constituents in walnuts to which such characteristics have been attributed (J. Nutr. 2014;144(4 Suppl):555S-60S).

Potential cutaneous applications

In 2010, Lee et al. assessed the effects of pedunculagin on 2,4,6-trinitrochlorobenzene (TNCB)-induced atopic dermatitis-like lesions in NC/Nga mice. Investigators applied a cream containing 0.1% or 0.5% pedunculagin to the positive treatment group; the negative treatment group received the base cream without pedunculagin, with no topical formulations administered to a control group. The investigators found, 4 weeks after treatment, that greater and more rapid improvement in the lesions was experienced by the group that received the higher concentration of pedunculagin (Skin Res. Technol. 2010;16:371-7).

Kim et al., in 2014, isolated pedunculagin and five other phenolic compounds from the leaves of Quercus mongolica (Mongolian oak). They found that pedunculagin exhibited strong in vitro inhibition against the expression of matrix metalloproteinase (MMP)-1 and increased type I procollagen in human fibroblasts exposed to UVB. The Q. mongolica constituent was also found to concentration-dependently exhibit potent scavenging activity against the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical. The investigators suggested that the ellagitannin shows promise for use in preventing and treating cutaneous aging (Arch. Pharm. Res. 2014 Feb. 7. [Epub ahead of print]).

Conclusion

Pedunculagin shows some promise as an agent that can yield dermatologic benefits. However, the body of research on this natural compound is relatively scant. More expansive follow-up work is needed to determine the extent to which pedunculagin can be reasonably incorporated into the dermatologic armamentarium.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Skin & Allergy News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy,Topix Pharmaceuticals, and Unilever.

Pedunculagin is an ellagitannin, a group of polyphenolic hydrolyzable tannins, found in various plants, including Emblica officinalis, Pimenta dioica, and several others (Arch. Pharm. Res. 2014, Feb 7. [Epub ahead of print]; Curr. Drug Targets 2012;13:1900-06). The substance is reported to exhibit anti-inflammatory, anticancer, and antimicrobial activities, and it is considered a potent dietary antioxidant (Z. Naturforsch C. 2007;62:526-36; J. Org. Chem. 1996;61:2606-12; J. Nutr. 2014;144(4 Suppl):555S-60S). Purified from the Manchurian alder (Alnus hirsuta), pedunculagin is also a novel immunomodulating agent (Skin Res. Technol. 2010;16:371-7). Pedunculagin is also one of the hydrolyzable tannins found in Punica granatum (pomegranate), fruit extracts of which have been shown by Afaq et al. to exert photochemopreventive effects against the deleterious effects of ultraviolet B radiation (Photochem. Photobiol. 2005;81:38-45). Pedunculagin was first synthesized (in 2,3- and 4,6-coupled form) in 1996 (J. Org. Chem. 1996;61:2606-12).

Anticancer and antioxidant activity

In a study of 57 tannins and related compounds, Kashiwada et al. noted in a 1992 study that pedunculagin exhibited selective cytotoxicity against melanoma cells (J. Nat. Prod. 1992;55:1033-43).

According to a 2007 report by Marzouk et al., pedunculagin is among one of several tannins identified in the leaves of Pimenta dioica, and it is among the most potent free radical scavengers, as well as one of the most cytotoxic substances against solid tumor cancer cells. Pedunculagin also was found to significantly suppress nitric oxide production and spur the proliferation of T-lymphocytes and macrophages (Z. Naturforsch C. 2007;62:526-36).

In 2012, Kähkönen et al. observed that red raspberry and cloudberry ellagitannins, including pedunculagin, acted as effective radical scavengers, substantially contributing to the antioxidant activity of the berries in lipoprotein and lipid emulsion environments (J. Agric. Food Chem. 2012;60:1167-74).

A 2014 review by Hardman summarized several studies suggesting that potent anticancer properties, including antiproliferative and antiangiogenic activities, have been linked to walnuts. She noted that pedunculagin is one of the key constituents in walnuts to which such characteristics have been attributed (J. Nutr. 2014;144(4 Suppl):555S-60S).

Potential cutaneous applications

In 2010, Lee et al. assessed the effects of pedunculagin on 2,4,6-trinitrochlorobenzene (TNCB)-induced atopic dermatitis-like lesions in NC/Nga mice. Investigators applied a cream containing 0.1% or 0.5% pedunculagin to the positive treatment group; the negative treatment group received the base cream without pedunculagin, with no topical formulations administered to a control group. The investigators found, 4 weeks after treatment, that greater and more rapid improvement in the lesions was experienced by the group that received the higher concentration of pedunculagin (Skin Res. Technol. 2010;16:371-7).

Kim et al., in 2014, isolated pedunculagin and five other phenolic compounds from the leaves of Quercus mongolica (Mongolian oak). They found that pedunculagin exhibited strong in vitro inhibition against the expression of matrix metalloproteinase (MMP)-1 and increased type I procollagen in human fibroblasts exposed to UVB. The Q. mongolica constituent was also found to concentration-dependently exhibit potent scavenging activity against the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical. The investigators suggested that the ellagitannin shows promise for use in preventing and treating cutaneous aging (Arch. Pharm. Res. 2014 Feb. 7. [Epub ahead of print]).

Conclusion

Pedunculagin shows some promise as an agent that can yield dermatologic benefits. However, the body of research on this natural compound is relatively scant. More expansive follow-up work is needed to determine the extent to which pedunculagin can be reasonably incorporated into the dermatologic armamentarium.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Skin & Allergy News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy,Topix Pharmaceuticals, and Unilever.

Pedunculagin is an ellagitannin, a group of polyphenolic hydrolyzable tannins, found in various plants, including Emblica officinalis, Pimenta dioica, and several others (Arch. Pharm. Res. 2014, Feb 7. [Epub ahead of print]; Curr. Drug Targets 2012;13:1900-06). The substance is reported to exhibit anti-inflammatory, anticancer, and antimicrobial activities, and it is considered a potent dietary antioxidant (Z. Naturforsch C. 2007;62:526-36; J. Org. Chem. 1996;61:2606-12; J. Nutr. 2014;144(4 Suppl):555S-60S). Purified from the Manchurian alder (Alnus hirsuta), pedunculagin is also a novel immunomodulating agent (Skin Res. Technol. 2010;16:371-7). Pedunculagin is also one of the hydrolyzable tannins found in Punica granatum (pomegranate), fruit extracts of which have been shown by Afaq et al. to exert photochemopreventive effects against the deleterious effects of ultraviolet B radiation (Photochem. Photobiol. 2005;81:38-45). Pedunculagin was first synthesized (in 2,3- and 4,6-coupled form) in 1996 (J. Org. Chem. 1996;61:2606-12).

Anticancer and antioxidant activity

In a study of 57 tannins and related compounds, Kashiwada et al. noted in a 1992 study that pedunculagin exhibited selective cytotoxicity against melanoma cells (J. Nat. Prod. 1992;55:1033-43).

According to a 2007 report by Marzouk et al., pedunculagin is among one of several tannins identified in the leaves of Pimenta dioica, and it is among the most potent free radical scavengers, as well as one of the most cytotoxic substances against solid tumor cancer cells. Pedunculagin also was found to significantly suppress nitric oxide production and spur the proliferation of T-lymphocytes and macrophages (Z. Naturforsch C. 2007;62:526-36).

In 2012, Kähkönen et al. observed that red raspberry and cloudberry ellagitannins, including pedunculagin, acted as effective radical scavengers, substantially contributing to the antioxidant activity of the berries in lipoprotein and lipid emulsion environments (J. Agric. Food Chem. 2012;60:1167-74).

A 2014 review by Hardman summarized several studies suggesting that potent anticancer properties, including antiproliferative and antiangiogenic activities, have been linked to walnuts. She noted that pedunculagin is one of the key constituents in walnuts to which such characteristics have been attributed (J. Nutr. 2014;144(4 Suppl):555S-60S).

Potential cutaneous applications

In 2010, Lee et al. assessed the effects of pedunculagin on 2,4,6-trinitrochlorobenzene (TNCB)-induced atopic dermatitis-like lesions in NC/Nga mice. Investigators applied a cream containing 0.1% or 0.5% pedunculagin to the positive treatment group; the negative treatment group received the base cream without pedunculagin, with no topical formulations administered to a control group. The investigators found, 4 weeks after treatment, that greater and more rapid improvement in the lesions was experienced by the group that received the higher concentration of pedunculagin (Skin Res. Technol. 2010;16:371-7).

Kim et al., in 2014, isolated pedunculagin and five other phenolic compounds from the leaves of Quercus mongolica (Mongolian oak). They found that pedunculagin exhibited strong in vitro inhibition against the expression of matrix metalloproteinase (MMP)-1 and increased type I procollagen in human fibroblasts exposed to UVB. The Q. mongolica constituent was also found to concentration-dependently exhibit potent scavenging activity against the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical. The investigators suggested that the ellagitannin shows promise for use in preventing and treating cutaneous aging (Arch. Pharm. Res. 2014 Feb. 7. [Epub ahead of print]).

Conclusion

Pedunculagin shows some promise as an agent that can yield dermatologic benefits. However, the body of research on this natural compound is relatively scant. More expansive follow-up work is needed to determine the extent to which pedunculagin can be reasonably incorporated into the dermatologic armamentarium.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002), and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Skin & Allergy News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy,Topix Pharmaceuticals, and Unilever.

CORONADO, CALIF.– In an analysis of primary treatments for all stages of differentiated thyroid carcinoma, only thyroid hormone suppressive therapy was associated with both improved overall survival and disease-free survival.

Further, when examining the degree of thyroid hormone suppressive therapy (THST), aggressive THST conferred no additional survival benefit when compared with moderate THST, even when limiting the analysis to patients with distant metastatic disease, results from a long-term analysis of registry showed.

Those are key findings from an updated analysis of data from the National Thyroid Cancer Treatment Cooperative Study Group Registry, which were presented by lead study author Dr. Aubrey Carhill during the annual meeting of the American Thyroid Association.

“To date there are no prospective studies evaluating the longitudinal outcomes of initial long-term therapies in differentiated thyroid carcinoma,” said Dr. Carhill of MD Anderson Cancer Center, Houston. “In the absence of prospective trials, there has been significant reliance on retrospective studies with limited numbers of patients and low event rates as well as significant reliance on expert opinion to guide clinical practice.”

For example, current ATA guidelines for TSH suppression suggest that in long-term follow-up of patients with differentiated thyroid cancer, “those with persistent disease should have TSH levels suppressed to undetectable levels and maintained indefinitely,” Dr. Carhill said, while disease-free, higher-risk patients “should be suppressed to low-moderate levels continued between 5 and 10 years and low-risk patients should be maintained in the low-normal range. Similar levels of evidence exist to support the use of radioactive iodine and the degree of surgical extent.”

The challenge for clinicians, she continued, becomes balancing the potential risks of more aggressive therapies, such as aggressive thyroid hormone suppression, and the risks associated with long-term thyrotoxicosis with the potential benefits of treatment. “This is not always clear, especially in patients who are at very low risk for cancer-specific mortality,” she said. “There remains a need for accurate prognostication in order to identify which patients will benefit from different treatment modalities because current staging systems have limited ability to predict response to treatment.”

Formed in 1987, the National Thyroid Treatment Cooperative Study Group is a multi-institutional effort to assess long-term management of outcomes on patients with differentiated thyroid cancer. The purpose of the present study was to provide a more current analysis of the prospectively collected data, which was last analyzed in 2001. All staging is tracked according to the registry’s staging system, which is very similar to that of the American Joint Committee on Cancer’s TNM Staging System. Therapies analyzed included total/near total thyroidectomy (T/NTT) vs. a lesser extent of surgery; radioactive iodine (RAI) vs. no RAI; and increasing degrees of THST over time.

Dr. Carhill presented findings from an analysis of the effects of initial therapies in 4,941 patients treated at 11 centers in North America between 1987 and 2012. The median length of follow-up was 6 years, which translated to 34,631 person-years of documented follow-up time. The researchers used univariate and multivariate analyses to assess overall and disease-free survival. Moderate THST was defined as TSH maintained in subnormal or normal levels, while aggressive THST was defined as that maintained in undetectable or subnormal levels.

Improved overall survival was observed in stage III patients who received RAI (risk ratio, 0.66; P = .04) and in stage IV patients who received T/NTT and RAI (RR, 0.66 and 0.70, respectively; combined P = .049). Moderate but not aggressive THST was associated with significantly improved overall survival in all stages (RR, 0.13 in stage I, 0.09 in stage II, 0.13 in stage III, and 0.33 in stage IV), as well as with improved disease-free survival (RR, 0.52 in stage I, 0.40 in stage II, 0.18 in stage III, and no RR in stage IV).

In stage I patients, RAI conferred worse disease-free survival (RR, 1.79; P = .0005). “However, further propensity analysis demonstrated that there was no difference in disease-free survival when patients were stratified according to their propensity to receive radioactive iodine,” Dr. Carhill said.

To evaluate the optimal duration of THST, the researchers examined the effect of continuing degrees of suppression beyond 1, 3, and 5 years of follow-up. After 1 and 3 years of follow-up, both initial stage and moderate TSH suppression were independently predictive of improved overall survival (RR, 0.31 and 0.29, respectively). However, after 5 years of follow-up, “although initial stage remained independently predictive, there was no further benefit with any subsequent degree of TSH suppression,” Dr. Carhill said.

The study “confirms prior registry findings of a survival benefit in high-risk groups treated with T/NTT and RAI, and there is no disease-free survival benefit in low-risk groups receiving postoperative RAI,” she concluded. “We also report for the first time that in multivariate analysis of primary treatments for DTC [differentiated thyroid cancer], in all stages, only THST was associated with both improved overall survival and disease-free survival. When examining the degree of THST, aggressive THST confers no additional survival advantage as compared with moderate THST, even in patients with distant metastatic disease, which remains particularly relevant given the risks associated with long-term thyrotoxicosis.” She acknowledged certain limitations of the study, including the potential for institutional bias. “However, we feel that this is somewhat offset due to the size of the registry cohort and the number of sites involved” Dr. Carhill said.

The registry has received support from Genzyme and Pfizer. Dr. Carhill reported having no financial disclosures.

[email protected]

On Twitter @dougbrunk

CORONADO, CALIF.– In an analysis of primary treatments for all stages of differentiated thyroid carcinoma, only thyroid hormone suppressive therapy was associated with both improved overall survival and disease-free survival.

Further, when examining the degree of thyroid hormone suppressive therapy (THST), aggressive THST conferred no additional survival benefit when compared with moderate THST, even when limiting the analysis to patients with distant metastatic disease, results from a long-term analysis of registry showed.

Those are key findings from an updated analysis of data from the National Thyroid Cancer Treatment Cooperative Study Group Registry, which were presented by lead study author Dr. Aubrey Carhill during the annual meeting of the American Thyroid Association.

“To date there are no prospective studies evaluating the longitudinal outcomes of initial long-term therapies in differentiated thyroid carcinoma,” said Dr. Carhill of MD Anderson Cancer Center, Houston. “In the absence of prospective trials, there has been significant reliance on retrospective studies with limited numbers of patients and low event rates as well as significant reliance on expert opinion to guide clinical practice.”

For example, current ATA guidelines for TSH suppression suggest that in long-term follow-up of patients with differentiated thyroid cancer, “those with persistent disease should have TSH levels suppressed to undetectable levels and maintained indefinitely,” Dr. Carhill said, while disease-free, higher-risk patients “should be suppressed to low-moderate levels continued between 5 and 10 years and low-risk patients should be maintained in the low-normal range. Similar levels of evidence exist to support the use of radioactive iodine and the degree of surgical extent.”

The challenge for clinicians, she continued, becomes balancing the potential risks of more aggressive therapies, such as aggressive thyroid hormone suppression, and the risks associated with long-term thyrotoxicosis with the potential benefits of treatment. “This is not always clear, especially in patients who are at very low risk for cancer-specific mortality,” she said. “There remains a need for accurate prognostication in order to identify which patients will benefit from different treatment modalities because current staging systems have limited ability to predict response to treatment.”

Formed in 1987, the National Thyroid Treatment Cooperative Study Group is a multi-institutional effort to assess long-term management of outcomes on patients with differentiated thyroid cancer. The purpose of the present study was to provide a more current analysis of the prospectively collected data, which was last analyzed in 2001. All staging is tracked according to the registry’s staging system, which is very similar to that of the American Joint Committee on Cancer’s TNM Staging System. Therapies analyzed included total/near total thyroidectomy (T/NTT) vs. a lesser extent of surgery; radioactive iodine (RAI) vs. no RAI; and increasing degrees of THST over time.

Dr. Carhill presented findings from an analysis of the effects of initial therapies in 4,941 patients treated at 11 centers in North America between 1987 and 2012. The median length of follow-up was 6 years, which translated to 34,631 person-years of documented follow-up time. The researchers used univariate and multivariate analyses to assess overall and disease-free survival. Moderate THST was defined as TSH maintained in subnormal or normal levels, while aggressive THST was defined as that maintained in undetectable or subnormal levels.

Improved overall survival was observed in stage III patients who received RAI (risk ratio, 0.66; P = .04) and in stage IV patients who received T/NTT and RAI (RR, 0.66 and 0.70, respectively; combined P = .049). Moderate but not aggressive THST was associated with significantly improved overall survival in all stages (RR, 0.13 in stage I, 0.09 in stage II, 0.13 in stage III, and 0.33 in stage IV), as well as with improved disease-free survival (RR, 0.52 in stage I, 0.40 in stage II, 0.18 in stage III, and no RR in stage IV).

In stage I patients, RAI conferred worse disease-free survival (RR, 1.79; P = .0005). “However, further propensity analysis demonstrated that there was no difference in disease-free survival when patients were stratified according to their propensity to receive radioactive iodine,” Dr. Carhill said.

To evaluate the optimal duration of THST, the researchers examined the effect of continuing degrees of suppression beyond 1, 3, and 5 years of follow-up. After 1 and 3 years of follow-up, both initial stage and moderate TSH suppression were independently predictive of improved overall survival (RR, 0.31 and 0.29, respectively). However, after 5 years of follow-up, “although initial stage remained independently predictive, there was no further benefit with any subsequent degree of TSH suppression,” Dr. Carhill said.

The study “confirms prior registry findings of a survival benefit in high-risk groups treated with T/NTT and RAI, and there is no disease-free survival benefit in low-risk groups receiving postoperative RAI,” she concluded. “We also report for the first time that in multivariate analysis of primary treatments for DTC [differentiated thyroid cancer], in all stages, only THST was associated with both improved overall survival and disease-free survival. When examining the degree of THST, aggressive THST confers no additional survival advantage as compared with moderate THST, even in patients with distant metastatic disease, which remains particularly relevant given the risks associated with long-term thyrotoxicosis.” She acknowledged certain limitations of the study, including the potential for institutional bias. “However, we feel that this is somewhat offset due to the size of the registry cohort and the number of sites involved” Dr. Carhill said.

The registry has received support from Genzyme and Pfizer. Dr. Carhill reported having no financial disclosures.

[email protected]

On Twitter @dougbrunk

CORONADO, CALIF.– In an analysis of primary treatments for all stages of differentiated thyroid carcinoma, only thyroid hormone suppressive therapy was associated with both improved overall survival and disease-free survival.

Further, when examining the degree of thyroid hormone suppressive therapy (THST), aggressive THST conferred no additional survival benefit when compared with moderate THST, even when limiting the analysis to patients with distant metastatic disease, results from a long-term analysis of registry showed.

Those are key findings from an updated analysis of data from the National Thyroid Cancer Treatment Cooperative Study Group Registry, which were presented by lead study author Dr. Aubrey Carhill during the annual meeting of the American Thyroid Association.

“To date there are no prospective studies evaluating the longitudinal outcomes of initial long-term therapies in differentiated thyroid carcinoma,” said Dr. Carhill of MD Anderson Cancer Center, Houston. “In the absence of prospective trials, there has been significant reliance on retrospective studies with limited numbers of patients and low event rates as well as significant reliance on expert opinion to guide clinical practice.”

For example, current ATA guidelines for TSH suppression suggest that in long-term follow-up of patients with differentiated thyroid cancer, “those with persistent disease should have TSH levels suppressed to undetectable levels and maintained indefinitely,” Dr. Carhill said, while disease-free, higher-risk patients “should be suppressed to low-moderate levels continued between 5 and 10 years and low-risk patients should be maintained in the low-normal range. Similar levels of evidence exist to support the use of radioactive iodine and the degree of surgical extent.”

The challenge for clinicians, she continued, becomes balancing the potential risks of more aggressive therapies, such as aggressive thyroid hormone suppression, and the risks associated with long-term thyrotoxicosis with the potential benefits of treatment. “This is not always clear, especially in patients who are at very low risk for cancer-specific mortality,” she said. “There remains a need for accurate prognostication in order to identify which patients will benefit from different treatment modalities because current staging systems have limited ability to predict response to treatment.”

Formed in 1987, the National Thyroid Treatment Cooperative Study Group is a multi-institutional effort to assess long-term management of outcomes on patients with differentiated thyroid cancer. The purpose of the present study was to provide a more current analysis of the prospectively collected data, which was last analyzed in 2001. All staging is tracked according to the registry’s staging system, which is very similar to that of the American Joint Committee on Cancer’s TNM Staging System. Therapies analyzed included total/near total thyroidectomy (T/NTT) vs. a lesser extent of surgery; radioactive iodine (RAI) vs. no RAI; and increasing degrees of THST over time.

Dr. Carhill presented findings from an analysis of the effects of initial therapies in 4,941 patients treated at 11 centers in North America between 1987 and 2012. The median length of follow-up was 6 years, which translated to 34,631 person-years of documented follow-up time. The researchers used univariate and multivariate analyses to assess overall and disease-free survival. Moderate THST was defined as TSH maintained in subnormal or normal levels, while aggressive THST was defined as that maintained in undetectable or subnormal levels.

Improved overall survival was observed in stage III patients who received RAI (risk ratio, 0.66; P = .04) and in stage IV patients who received T/NTT and RAI (RR, 0.66 and 0.70, respectively; combined P = .049). Moderate but not aggressive THST was associated with significantly improved overall survival in all stages (RR, 0.13 in stage I, 0.09 in stage II, 0.13 in stage III, and 0.33 in stage IV), as well as with improved disease-free survival (RR, 0.52 in stage I, 0.40 in stage II, 0.18 in stage III, and no RR in stage IV).

In stage I patients, RAI conferred worse disease-free survival (RR, 1.79; P = .0005). “However, further propensity analysis demonstrated that there was no difference in disease-free survival when patients were stratified according to their propensity to receive radioactive iodine,” Dr. Carhill said.

To evaluate the optimal duration of THST, the researchers examined the effect of continuing degrees of suppression beyond 1, 3, and 5 years of follow-up. After 1 and 3 years of follow-up, both initial stage and moderate TSH suppression were independently predictive of improved overall survival (RR, 0.31 and 0.29, respectively). However, after 5 years of follow-up, “although initial stage remained independently predictive, there was no further benefit with any subsequent degree of TSH suppression,” Dr. Carhill said.

The study “confirms prior registry findings of a survival benefit in high-risk groups treated with T/NTT and RAI, and there is no disease-free survival benefit in low-risk groups receiving postoperative RAI,” she concluded. “We also report for the first time that in multivariate analysis of primary treatments for DTC [differentiated thyroid cancer], in all stages, only THST was associated with both improved overall survival and disease-free survival. When examining the degree of THST, aggressive THST confers no additional survival advantage as compared with moderate THST, even in patients with distant metastatic disease, which remains particularly relevant given the risks associated with long-term thyrotoxicosis.” She acknowledged certain limitations of the study, including the potential for institutional bias. “However, we feel that this is somewhat offset due to the size of the registry cohort and the number of sites involved” Dr. Carhill said.

The registry has received support from Genzyme and Pfizer. Dr. Carhill reported having no financial disclosures.

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On Twitter @dougbrunk

Hands-on workshop helps hospitalists gain confidence in fundamentals, learn to teach physical exam skills better

Hands-on workshop helps hospitalists gain confidence in fundamentals, learn to teach physical exam skills better

Hands-on workshop helps hospitalists gain confidence in fundamentals, learn to teach physical exam skills better