Lab mouse

Cutting certain amino acids from the diet slows tumor growth and prolongs survival in mouse models of malignancy, according to research published in Nature.

Researchers found that removing 2 non-essential amino acids—serine and glycine (SG)—from the diet of mice slowed the development of lymphoma and intestinal cancer.

The SG-free diet also made lymphoma more susceptible to reactive oxygen species (ROS).

As chemotherapy and radiotherapy boost levels of ROS, the researchers believe an SG-free diet could make conventional cancer treatments more effective.

“Our findings suggest that restricting specific amino acids through a controlled diet plan could be an additional part of treatment for some cancer patients in future, helping to make other treatments more effective,” said study author Oliver Maddocks, PhD, of the University of Glasgow in the UK.

He and his colleagues tested the SG-free diet in mouse models of lymphoma (Eμ-Myc) and observed decreased tumor volume and lymphoma cell numbers as well as a significant improvement in survival compared to controls.

The median survival (from the time of diet change at day 60) was 192 days for mice on the SG-free diet and 59 days for mice on the control diet (P=0.0367).

To test whether increasing ROS could enhance the anticancer effects of the SG-free diet, the researchers crossed Eμ-Myc mice with mice that don’t express Tigar, a protein that can support tumor development by limiting ROS.

The researchers found that Tigar ^-/- mice on the SG-free diet had significantly better survival than Tigar ^-/- mice on the control diet (P=0.0451).

The median survival was 50.5 days for Tigar ^+/+ mice on the control diet, 80 days for Tigar ^+/+ mice on the SG-free diet, 107 days for Tigar ^-/- mice on the control diet, and 226 days for Tigar ^-/- mice on the SG-free diet.

The researchers also found the SG-free diet was less effective in cancers with an activated Kras gene (such as prostate cancer) because the faulty gene boosted the cancer cells’ ability to make their own serine and glycine. The team said this could help in selecting which tumors could be best targeted by diet therapy.

“This is a really interesting look at how cutting off the supply of nutrients essential to cancer cell growth and division could help restrain tumors,” said Emma Smith, PhD, of Cancer Research UK, which funded this study.

“The next steps are clinical trials in people to see if giving a specialized diet that lacks these amino acids is safe and helps slow tumor growth as seen in mice. We’d also need to work out which patients are most likely to benefit, depending on the characteristics of their cancer.”

Lab mouse

Cutting certain amino acids from the diet slows tumor growth and prolongs survival in mouse models of malignancy, according to research published in Nature.

Researchers found that removing 2 non-essential amino acids—serine and glycine (SG)—from the diet of mice slowed the development of lymphoma and intestinal cancer.

The SG-free diet also made lymphoma more susceptible to reactive oxygen species (ROS).

As chemotherapy and radiotherapy boost levels of ROS, the researchers believe an SG-free diet could make conventional cancer treatments more effective.

“Our findings suggest that restricting specific amino acids through a controlled diet plan could be an additional part of treatment for some cancer patients in future, helping to make other treatments more effective,” said study author Oliver Maddocks, PhD, of the University of Glasgow in the UK.

He and his colleagues tested the SG-free diet in mouse models of lymphoma (Eμ-Myc) and observed decreased tumor volume and lymphoma cell numbers as well as a significant improvement in survival compared to controls.

The median survival (from the time of diet change at day 60) was 192 days for mice on the SG-free diet and 59 days for mice on the control diet (P=0.0367).

To test whether increasing ROS could enhance the anticancer effects of the SG-free diet, the researchers crossed Eμ-Myc mice with mice that don’t express Tigar, a protein that can support tumor development by limiting ROS.

The researchers found that Tigar ^-/- mice on the SG-free diet had significantly better survival than Tigar ^-/- mice on the control diet (P=0.0451).

The median survival was 50.5 days for Tigar ^+/+ mice on the control diet, 80 days for Tigar ^+/+ mice on the SG-free diet, 107 days for Tigar ^-/- mice on the control diet, and 226 days for Tigar ^-/- mice on the SG-free diet.

The researchers also found the SG-free diet was less effective in cancers with an activated Kras gene (such as prostate cancer) because the faulty gene boosted the cancer cells’ ability to make their own serine and glycine. The team said this could help in selecting which tumors could be best targeted by diet therapy.

“This is a really interesting look at how cutting off the supply of nutrients essential to cancer cell growth and division could help restrain tumors,” said Emma Smith, PhD, of Cancer Research UK, which funded this study.

“The next steps are clinical trials in people to see if giving a specialized diet that lacks these amino acids is safe and helps slow tumor growth as seen in mice. We’d also need to work out which patients are most likely to benefit, depending on the characteristics of their cancer.”

Lab mouse

Cutting certain amino acids from the diet slows tumor growth and prolongs survival in mouse models of malignancy, according to research published in Nature.

Researchers found that removing 2 non-essential amino acids—serine and glycine (SG)—from the diet of mice slowed the development of lymphoma and intestinal cancer.

The SG-free diet also made lymphoma more susceptible to reactive oxygen species (ROS).

As chemotherapy and radiotherapy boost levels of ROS, the researchers believe an SG-free diet could make conventional cancer treatments more effective.

“Our findings suggest that restricting specific amino acids through a controlled diet plan could be an additional part of treatment for some cancer patients in future, helping to make other treatments more effective,” said study author Oliver Maddocks, PhD, of the University of Glasgow in the UK.

He and his colleagues tested the SG-free diet in mouse models of lymphoma (Eμ-Myc) and observed decreased tumor volume and lymphoma cell numbers as well as a significant improvement in survival compared to controls.

The median survival (from the time of diet change at day 60) was 192 days for mice on the SG-free diet and 59 days for mice on the control diet (P=0.0367).

To test whether increasing ROS could enhance the anticancer effects of the SG-free diet, the researchers crossed Eμ-Myc mice with mice that don’t express Tigar, a protein that can support tumor development by limiting ROS.

The researchers found that Tigar ^-/- mice on the SG-free diet had significantly better survival than Tigar ^-/- mice on the control diet (P=0.0451).

The median survival was 50.5 days for Tigar ^+/+ mice on the control diet, 80 days for Tigar ^+/+ mice on the SG-free diet, 107 days for Tigar ^-/- mice on the control diet, and 226 days for Tigar ^-/- mice on the SG-free diet.

The researchers also found the SG-free diet was less effective in cancers with an activated Kras gene (such as prostate cancer) because the faulty gene boosted the cancer cells’ ability to make their own serine and glycine. The team said this could help in selecting which tumors could be best targeted by diet therapy.

“This is a really interesting look at how cutting off the supply of nutrients essential to cancer cell growth and division could help restrain tumors,” said Emma Smith, PhD, of Cancer Research UK, which funded this study.

“The next steps are clinical trials in people to see if giving a specialized diet that lacks these amino acids is safe and helps slow tumor growth as seen in mice. We’d also need to work out which patients are most likely to benefit, depending on the characteristics of their cancer.”

Photo by Daniel Gay

A new type of hemoglobin-based oxygen carrier has shown early promise as a potential blood substitute, according to researchers.

The team created nanoparticles consisting of bovine hemoglobin coated with the polymer polydopamine (PDA).

Lab tests showed that hemoglobin-PDA nanoparticles effectively carried oxygen, caused minimal cell damage, and acted as antioxidants, scavenging for potentially damaging free radicals and reactive oxygen species (ROS).

Hong Zhou, PhD, of the Beijing Institute of Transfusion Medicine in China, and colleagues reported these results in Biomacromolecules.

Past attempts to develop chemically modified hemoglobin as a blood substitute have been hindered by the formation of methemoglobin.

Methemoglobin doesn’t bind oxygen and therefore decreases the amount of oxygen blood delivers in the body. In addition, the generation of methemoglobin produces hydrogen peroxide, which leads to cell damage.

Dr Zhou and colleagues wanted to see if packaging hemoglobin in a benign envelope could prevent these problems. So the team developed a one-step method for wrapping hemoglobin—extracted from bovine red cells—in PDA.

The researchers said their simple preparation method meant the nanoparticles maintained the integrity of hemoglobin’s chemical structure without introducing any toxic reagent.

In addition, the PDA coating allowed hemoglobin to maintain its oxygen-carrying ability by preventing the formation of methemoglobin.

The researchers found the hemoglobin-PDA nanoparticles to have “excellent antioxidant capacity,” as they scavenged free radicals. The team said the ABTS+ radical scavenging rate reached 89%, and the DPPH radical scavenging rate reached 49%.

The hemoglobin-PDA nanoparticles also demonstrated antioxidant capacity by suppressing ROS generation. They reduced hydrogen peroxide-induced ROS generation in H9c2 cells.

Furthermore, the hemoglobin-PDA nanoparticles had little effect on blood constituents and cell viability.

The researchers found the nanoparticles had minimal effects on platelet aggregation, hemolysis in red blood cells, and coagulation processes.

And the nanoparticles had no significant cytotoxic effects on human umbilical vein endothelial cells.

The researchers therefore concluded that their hemoglobin-PDA nanoparticles represent “promising progress” for hemoglobin-based oxygen carriers.

Photo by Daniel Gay

A new type of hemoglobin-based oxygen carrier has shown early promise as a potential blood substitute, according to researchers.

The team created nanoparticles consisting of bovine hemoglobin coated with the polymer polydopamine (PDA).

Lab tests showed that hemoglobin-PDA nanoparticles effectively carried oxygen, caused minimal cell damage, and acted as antioxidants, scavenging for potentially damaging free radicals and reactive oxygen species (ROS).

Hong Zhou, PhD, of the Beijing Institute of Transfusion Medicine in China, and colleagues reported these results in Biomacromolecules.

Past attempts to develop chemically modified hemoglobin as a blood substitute have been hindered by the formation of methemoglobin.

Methemoglobin doesn’t bind oxygen and therefore decreases the amount of oxygen blood delivers in the body. In addition, the generation of methemoglobin produces hydrogen peroxide, which leads to cell damage.

Dr Zhou and colleagues wanted to see if packaging hemoglobin in a benign envelope could prevent these problems. So the team developed a one-step method for wrapping hemoglobin—extracted from bovine red cells—in PDA.

The researchers said their simple preparation method meant the nanoparticles maintained the integrity of hemoglobin’s chemical structure without introducing any toxic reagent.

In addition, the PDA coating allowed hemoglobin to maintain its oxygen-carrying ability by preventing the formation of methemoglobin.

The researchers found the hemoglobin-PDA nanoparticles to have “excellent antioxidant capacity,” as they scavenged free radicals. The team said the ABTS+ radical scavenging rate reached 89%, and the DPPH radical scavenging rate reached 49%.

The hemoglobin-PDA nanoparticles also demonstrated antioxidant capacity by suppressing ROS generation. They reduced hydrogen peroxide-induced ROS generation in H9c2 cells.

Furthermore, the hemoglobin-PDA nanoparticles had little effect on blood constituents and cell viability.

The researchers found the nanoparticles had minimal effects on platelet aggregation, hemolysis in red blood cells, and coagulation processes.

And the nanoparticles had no significant cytotoxic effects on human umbilical vein endothelial cells.

The researchers therefore concluded that their hemoglobin-PDA nanoparticles represent “promising progress” for hemoglobin-based oxygen carriers.

Photo by Daniel Gay

A new type of hemoglobin-based oxygen carrier has shown early promise as a potential blood substitute, according to researchers.

The team created nanoparticles consisting of bovine hemoglobin coated with the polymer polydopamine (PDA).

Lab tests showed that hemoglobin-PDA nanoparticles effectively carried oxygen, caused minimal cell damage, and acted as antioxidants, scavenging for potentially damaging free radicals and reactive oxygen species (ROS).

Hong Zhou, PhD, of the Beijing Institute of Transfusion Medicine in China, and colleagues reported these results in Biomacromolecules.

Past attempts to develop chemically modified hemoglobin as a blood substitute have been hindered by the formation of methemoglobin.

Methemoglobin doesn’t bind oxygen and therefore decreases the amount of oxygen blood delivers in the body. In addition, the generation of methemoglobin produces hydrogen peroxide, which leads to cell damage.

Dr Zhou and colleagues wanted to see if packaging hemoglobin in a benign envelope could prevent these problems. So the team developed a one-step method for wrapping hemoglobin—extracted from bovine red cells—in PDA.

The researchers said their simple preparation method meant the nanoparticles maintained the integrity of hemoglobin’s chemical structure without introducing any toxic reagent.

In addition, the PDA coating allowed hemoglobin to maintain its oxygen-carrying ability by preventing the formation of methemoglobin.

The researchers found the hemoglobin-PDA nanoparticles to have “excellent antioxidant capacity,” as they scavenged free radicals. The team said the ABTS+ radical scavenging rate reached 89%, and the DPPH radical scavenging rate reached 49%.

The hemoglobin-PDA nanoparticles also demonstrated antioxidant capacity by suppressing ROS generation. They reduced hydrogen peroxide-induced ROS generation in H9c2 cells.

Furthermore, the hemoglobin-PDA nanoparticles had little effect on blood constituents and cell viability.

The researchers found the nanoparticles had minimal effects on platelet aggregation, hemolysis in red blood cells, and coagulation processes.

And the nanoparticles had no significant cytotoxic effects on human umbilical vein endothelial cells.

The researchers therefore concluded that their hemoglobin-PDA nanoparticles represent “promising progress” for hemoglobin-based oxygen carriers.

The FP suspected contact dermatitis, but also noted that the patient had white material between his fingers and performed a potassium hydroxide (KOH) preparation. (See a video on how to perform a KOH preparation here: http://www.mdedge.com/jfponline/article/100603/dermatology/koh-preparation.) Under the microscope, the FP found budding yeast and the pseudohyphae of Candida albicans. Candida in the interdigital space is called erosio interdigitalis blastomycetica.

Patients with diabetes are at higher risk for this condition, as are those who perform “wet work.” The FP discussed the importance of hand protection with the patient and ways to better control his diabetes.

Fortunately, the patient had the next 2 days off of work so he was able to begin his treatment while avoiding the irritating environment at work. The FP recommended that the patient purchase over-the-counter clotrimazole cream to apply between his fingers. He also prescribed 0.1% triamcinolone ointment to be applied twice daily and discussed the use of protective gloves with cotton liners whenever possible.

The FP also referred the patient to Dermatology for further evaluation of the suspected contact dermatitis (including patch testing).

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Hand eczema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:597-602.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP suspected contact dermatitis, but also noted that the patient had white material between his fingers and performed a potassium hydroxide (KOH) preparation. (See a video on how to perform a KOH preparation here: http://www.mdedge.com/jfponline/article/100603/dermatology/koh-preparation.) Under the microscope, the FP found budding yeast and the pseudohyphae of Candida albicans. Candida in the interdigital space is called erosio interdigitalis blastomycetica.

Patients with diabetes are at higher risk for this condition, as are those who perform “wet work.” The FP discussed the importance of hand protection with the patient and ways to better control his diabetes.

Fortunately, the patient had the next 2 days off of work so he was able to begin his treatment while avoiding the irritating environment at work. The FP recommended that the patient purchase over-the-counter clotrimazole cream to apply between his fingers. He also prescribed 0.1% triamcinolone ointment to be applied twice daily and discussed the use of protective gloves with cotton liners whenever possible.

The FP also referred the patient to Dermatology for further evaluation of the suspected contact dermatitis (including patch testing).

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Hand eczema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:597-602.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP suspected contact dermatitis, but also noted that the patient had white material between his fingers and performed a potassium hydroxide (KOH) preparation. (See a video on how to perform a KOH preparation here: http://www.mdedge.com/jfponline/article/100603/dermatology/koh-preparation.) Under the microscope, the FP found budding yeast and the pseudohyphae of Candida albicans. Candida in the interdigital space is called erosio interdigitalis blastomycetica.

Patients with diabetes are at higher risk for this condition, as are those who perform “wet work.” The FP discussed the importance of hand protection with the patient and ways to better control his diabetes.

Fortunately, the patient had the next 2 days off of work so he was able to begin his treatment while avoiding the irritating environment at work. The FP recommended that the patient purchase over-the-counter clotrimazole cream to apply between his fingers. He also prescribed 0.1% triamcinolone ointment to be applied twice daily and discussed the use of protective gloves with cotton liners whenever possible.

The FP also referred the patient to Dermatology for further evaluation of the suspected contact dermatitis (including patch testing).

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Hand eczema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:597-602.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

Shunt occlusion has been a well-documented cause of shunt failure in newborns who have had systemic to pulmonary shunt placement, and little has been known about why shunts occlude. However, researchers have reported in a small retrospective study that higher postoperative hematocrit levels immediately after surgery may be predictors of shunt occlusion.

Reporting in the April 2017 issue of The Journal of Thoracic and Cardiovascular Surgery, Brett R. Anderson, MD, of New York-Presbyterian/Morgan Stanley Children’s Hospital, Columbia University Medical Center in New York, and coauthors, found that every 5-point increase in postoperative hematocrit more than doubled an infant’s odds of having early shunt occlusion (J Thorac Cardiovasc Surg. 2017;153:947-55).

“Beginning in the latter half of 2014, we noticed an increase in the incidence of early shunt occlusions in our neonatal cardiac intensive care unit,” Dr. Anderson and coauthors said. So they conducted a retrospective chart review of 80 infants who had undergone systemic to pulmonary shunt placement from January 2010 to July 2015, hypothesizing that increased hematocrit in the early postoperative period might have caused early shunt occlusion. They investigated the association between the first postoperative hematocrit and early shunt occlusion and in-hospital mortality in these patients.

Five patients (6.3%) experienced early shunt occlusion – that is, within 24 hours of placement (actually, within 10 hours of placement). Overall, 12 infants (15%) experienced shunt occlusion. The physicians at New York-Presbyterian do not administer anticoagulation in these patients during the first 12 hours after shunt placement.

The median initial postoperative hematocrit was 41.7%, with a range of 31.7%-55.8%. The survival analysis the researchers performed found that for every 5 additional percentage points, the hazard ratio for early shunt occlusion was 2.7 (P = .007) and 1.74 for any shunt occlusion (P less than .001). Incidentally, four cases of early shunt occlusion occurred in the later study period after 2014, during which the average first postoperative hematocrit was significantly higher than in the pre-2014 study period, 45.3% vs. 41.5% (P = .21), and the odds of early shunt occlusion were 16 times higher (P less than .001). Dr. Anderson and coauthors said the possible explanation for this variation was a switch to a new point-of-care analyzer in 2013.

With regard to mortality, six infants overall (7.4%) died before discharge, and four (5%) within 30 days of shunt placement. No infants with early shunt occlusion died, although two with late shunt occlusion died. Increased inotrope score and first postoperative arterial oxygen tension were the only factors associated with increased mortality. “No significant association was identified between hematocrit and 30-day mortality,” Dr. Anderson and coauthors said.

In the first 24 hours after surgery, 11 infants (13.8%) received packed red blood cell (PRBC) transfusions, seven (8.8%) received platelets, and four (5%) received fresh frozen plasma/cryoprecipitate. Higher postoperative PRBC transfusion volumes were associated with increased odds of mortality (P = .001), but none of these factors were significantly associated with early shunt occlusion.

Dr. Anderson and coauthors acknowledged that shunt occlusion is a “vexing problem” in infants with cyanotic heart disease. While other researchers studied postoperative hematocrit levels and possible associations with outcomes, including shunt occlusion and mortality, the New York-Presbyterian investigators said this is the first study of the first postoperative hematocrit.

Dr. Anderson and coauthors said their findings raise the question about the ideal perioperative prophylactic antithrombotic therapy in these patients. These researchers initiate aspirin therapy 12 hours after surgery if hemostasis is established.

As a result of this study, Dr. Anderson and coauthors instituted a number of practice changes at their center. They include:

• Cardiac anesthesiologists have been asked not to transfuse shunted neonates with hematocrit level of greater than or equal to 35%, and hematocrits are then immediately repeated when a patient returns to the cardiac ICU.

• Patients with hematocrits greater than or equal to 55% get partial exchange transfusions.

• An individualized approach for patients with lower hematocrits who are more cyanotic than expected. This includes a diagnostic echocardiogram, nitric oxide, oxygen and heparin, escalated inotropic support if necessary and sometimes a cautious approach to transfusions if symptoms do not resolve and an acute shunt occlusion if not likely.

Dr. Anderson and coauthors acknowledged limits to their study, most notably its retrospective nature and a small population at a single center, and that large investigations are needed to validate their findings.

Dr. Anderson disclosed receiving salary support from the National Center for Advancing Translational Sciences. Coauthor Jennifer M. Duchon, MDCM, MPH, receives salary support from the National Institute of Allergy and Infectious Disease. The remaining coauthors had no financial relationships to disclose.

Shunt occlusion has been a well-documented cause of shunt failure in newborns who have had systemic to pulmonary shunt placement, and little has been known about why shunts occlude. However, researchers have reported in a small retrospective study that higher postoperative hematocrit levels immediately after surgery may be predictors of shunt occlusion.

Reporting in the April 2017 issue of The Journal of Thoracic and Cardiovascular Surgery, Brett R. Anderson, MD, of New York-Presbyterian/Morgan Stanley Children’s Hospital, Columbia University Medical Center in New York, and coauthors, found that every 5-point increase in postoperative hematocrit more than doubled an infant’s odds of having early shunt occlusion (J Thorac Cardiovasc Surg. 2017;153:947-55).

“Beginning in the latter half of 2014, we noticed an increase in the incidence of early shunt occlusions in our neonatal cardiac intensive care unit,” Dr. Anderson and coauthors said. So they conducted a retrospective chart review of 80 infants who had undergone systemic to pulmonary shunt placement from January 2010 to July 2015, hypothesizing that increased hematocrit in the early postoperative period might have caused early shunt occlusion. They investigated the association between the first postoperative hematocrit and early shunt occlusion and in-hospital mortality in these patients.

Five patients (6.3%) experienced early shunt occlusion – that is, within 24 hours of placement (actually, within 10 hours of placement). Overall, 12 infants (15%) experienced shunt occlusion. The physicians at New York-Presbyterian do not administer anticoagulation in these patients during the first 12 hours after shunt placement.

The median initial postoperative hematocrit was 41.7%, with a range of 31.7%-55.8%. The survival analysis the researchers performed found that for every 5 additional percentage points, the hazard ratio for early shunt occlusion was 2.7 (P = .007) and 1.74 for any shunt occlusion (P less than .001). Incidentally, four cases of early shunt occlusion occurred in the later study period after 2014, during which the average first postoperative hematocrit was significantly higher than in the pre-2014 study period, 45.3% vs. 41.5% (P = .21), and the odds of early shunt occlusion were 16 times higher (P less than .001). Dr. Anderson and coauthors said the possible explanation for this variation was a switch to a new point-of-care analyzer in 2013.

With regard to mortality, six infants overall (7.4%) died before discharge, and four (5%) within 30 days of shunt placement. No infants with early shunt occlusion died, although two with late shunt occlusion died. Increased inotrope score and first postoperative arterial oxygen tension were the only factors associated with increased mortality. “No significant association was identified between hematocrit and 30-day mortality,” Dr. Anderson and coauthors said.

In the first 24 hours after surgery, 11 infants (13.8%) received packed red blood cell (PRBC) transfusions, seven (8.8%) received platelets, and four (5%) received fresh frozen plasma/cryoprecipitate. Higher postoperative PRBC transfusion volumes were associated with increased odds of mortality (P = .001), but none of these factors were significantly associated with early shunt occlusion.

Dr. Anderson and coauthors acknowledged that shunt occlusion is a “vexing problem” in infants with cyanotic heart disease. While other researchers studied postoperative hematocrit levels and possible associations with outcomes, including shunt occlusion and mortality, the New York-Presbyterian investigators said this is the first study of the first postoperative hematocrit.

Dr. Anderson and coauthors said their findings raise the question about the ideal perioperative prophylactic antithrombotic therapy in these patients. These researchers initiate aspirin therapy 12 hours after surgery if hemostasis is established.

As a result of this study, Dr. Anderson and coauthors instituted a number of practice changes at their center. They include:

• Cardiac anesthesiologists have been asked not to transfuse shunted neonates with hematocrit level of greater than or equal to 35%, and hematocrits are then immediately repeated when a patient returns to the cardiac ICU.

• Patients with hematocrits greater than or equal to 55% get partial exchange transfusions.

• An individualized approach for patients with lower hematocrits who are more cyanotic than expected. This includes a diagnostic echocardiogram, nitric oxide, oxygen and heparin, escalated inotropic support if necessary and sometimes a cautious approach to transfusions if symptoms do not resolve and an acute shunt occlusion if not likely.

Dr. Anderson and coauthors acknowledged limits to their study, most notably its retrospective nature and a small population at a single center, and that large investigations are needed to validate their findings.

Dr. Anderson disclosed receiving salary support from the National Center for Advancing Translational Sciences. Coauthor Jennifer M. Duchon, MDCM, MPH, receives salary support from the National Institute of Allergy and Infectious Disease. The remaining coauthors had no financial relationships to disclose.

Shunt occlusion has been a well-documented cause of shunt failure in newborns who have had systemic to pulmonary shunt placement, and little has been known about why shunts occlude. However, researchers have reported in a small retrospective study that higher postoperative hematocrit levels immediately after surgery may be predictors of shunt occlusion.

Reporting in the April 2017 issue of The Journal of Thoracic and Cardiovascular Surgery, Brett R. Anderson, MD, of New York-Presbyterian/Morgan Stanley Children’s Hospital, Columbia University Medical Center in New York, and coauthors, found that every 5-point increase in postoperative hematocrit more than doubled an infant’s odds of having early shunt occlusion (J Thorac Cardiovasc Surg. 2017;153:947-55).

“Beginning in the latter half of 2014, we noticed an increase in the incidence of early shunt occlusions in our neonatal cardiac intensive care unit,” Dr. Anderson and coauthors said. So they conducted a retrospective chart review of 80 infants who had undergone systemic to pulmonary shunt placement from January 2010 to July 2015, hypothesizing that increased hematocrit in the early postoperative period might have caused early shunt occlusion. They investigated the association between the first postoperative hematocrit and early shunt occlusion and in-hospital mortality in these patients.

Five patients (6.3%) experienced early shunt occlusion – that is, within 24 hours of placement (actually, within 10 hours of placement). Overall, 12 infants (15%) experienced shunt occlusion. The physicians at New York-Presbyterian do not administer anticoagulation in these patients during the first 12 hours after shunt placement.

The median initial postoperative hematocrit was 41.7%, with a range of 31.7%-55.8%. The survival analysis the researchers performed found that for every 5 additional percentage points, the hazard ratio for early shunt occlusion was 2.7 (P = .007) and 1.74 for any shunt occlusion (P less than .001). Incidentally, four cases of early shunt occlusion occurred in the later study period after 2014, during which the average first postoperative hematocrit was significantly higher than in the pre-2014 study period, 45.3% vs. 41.5% (P = .21), and the odds of early shunt occlusion were 16 times higher (P less than .001). Dr. Anderson and coauthors said the possible explanation for this variation was a switch to a new point-of-care analyzer in 2013.

With regard to mortality, six infants overall (7.4%) died before discharge, and four (5%) within 30 days of shunt placement. No infants with early shunt occlusion died, although two with late shunt occlusion died. Increased inotrope score and first postoperative arterial oxygen tension were the only factors associated with increased mortality. “No significant association was identified between hematocrit and 30-day mortality,” Dr. Anderson and coauthors said.

In the first 24 hours after surgery, 11 infants (13.8%) received packed red blood cell (PRBC) transfusions, seven (8.8%) received platelets, and four (5%) received fresh frozen plasma/cryoprecipitate. Higher postoperative PRBC transfusion volumes were associated with increased odds of mortality (P = .001), but none of these factors were significantly associated with early shunt occlusion.

Dr. Anderson and coauthors acknowledged that shunt occlusion is a “vexing problem” in infants with cyanotic heart disease. While other researchers studied postoperative hematocrit levels and possible associations with outcomes, including shunt occlusion and mortality, the New York-Presbyterian investigators said this is the first study of the first postoperative hematocrit.

Dr. Anderson and coauthors said their findings raise the question about the ideal perioperative prophylactic antithrombotic therapy in these patients. These researchers initiate aspirin therapy 12 hours after surgery if hemostasis is established.

As a result of this study, Dr. Anderson and coauthors instituted a number of practice changes at their center. They include:

• Cardiac anesthesiologists have been asked not to transfuse shunted neonates with hematocrit level of greater than or equal to 35%, and hematocrits are then immediately repeated when a patient returns to the cardiac ICU.

• Patients with hematocrits greater than or equal to 55% get partial exchange transfusions.

• An individualized approach for patients with lower hematocrits who are more cyanotic than expected. This includes a diagnostic echocardiogram, nitric oxide, oxygen and heparin, escalated inotropic support if necessary and sometimes a cautious approach to transfusions if symptoms do not resolve and an acute shunt occlusion if not likely.

Dr. Anderson and coauthors acknowledged limits to their study, most notably its retrospective nature and a small population at a single center, and that large investigations are needed to validate their findings.

Dr. Anderson disclosed receiving salary support from the National Center for Advancing Translational Sciences. Coauthor Jennifer M. Duchon, MDCM, MPH, receives salary support from the National Institute of Allergy and Infectious Disease. The remaining coauthors had no financial relationships to disclose.

A short course of prednisolone may help rheumatologists differentiate between patients with rheumatoid arthritis and osteoarthritis, a proof of concept study shows.

However, the investigators caution that a positive response to the 3-day steroid course does not confirm a diagnosis of rheumatoid arthritis (RA).

For many years, rheumatologists have been using short courses of prednisolone in unclear clinical situations to differentiate between inflammatory and non-inflammatory arthritis, according to the investigators led by Uta Kiltz, MD, from Rheumazentrum Ruhrgebiet, Herne, Germany.

A short course of prednisolone may help rheumatologists differentiate between patients with rheumatoid arthritis and osteoarthritis, a proof of concept study shows.

However, the investigators caution that a positive response to the 3-day steroid course does not confirm a diagnosis of rheumatoid arthritis (RA).

For many years, rheumatologists have been using short courses of prednisolone in unclear clinical situations to differentiate between inflammatory and non-inflammatory arthritis, according to the investigators led by Uta Kiltz, MD, from Rheumazentrum Ruhrgebiet, Herne, Germany.

A short course of prednisolone may help rheumatologists differentiate between patients with rheumatoid arthritis and osteoarthritis, a proof of concept study shows.

However, the investigators caution that a positive response to the 3-day steroid course does not confirm a diagnosis of rheumatoid arthritis (RA).

For many years, rheumatologists have been using short courses of prednisolone in unclear clinical situations to differentiate between inflammatory and non-inflammatory arthritis, according to the investigators led by Uta Kiltz, MD, from Rheumazentrum Ruhrgebiet, Herne, Germany.

WASHINGTON – Orbital atherectomy (OA) was associated with a lower risk of in-hospital mortality than rotational atherectomy (RA) in female, obese, and elderly study groups, according to data from a prospective observational study.

Each procedure was employed to treat coronary artery calcifications (CAC) in the elderly and the obese prior to percutaneous interventions (PCI).

The data comparing OA with RA in these populations were drawn from the Clinical Outcomes of Atherectomy Prior to PCI (COAP) study, for which Perwaiz M. Meraj, MD, director of structural heart and peripheral vascular disease at the North Shore-LIJ Hospital, Manhasset, N.Y., served as the senior author.

Each set of data, as well as a third set of data comparing OA to RA in female patients, was presented separately at CRT 2017, sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

In the comparison of OA to RA in the elderly, a substudy known as COAP-75, the focus was on patients 75 years of age or older who underwent either OA or RA to remove calcified coronary lesions within the context of PCI. As with the obese and female subgroups, the elderly patients in this study were drawn from 35,590 patients who underwent PCI at one of five tertiary care hospitals in a recent 5-year period.

Of the 310 elderly patients undergoing atherectomy, 117 were treated with OA and 193 with RA. The median lesion lengths and diameters were not significantly different between the two groups. Although OA was less likely to be performed through femoral access (53% vs. 68.9%; P = .005), no other measured differences in procedure were significant, with one exception: Fluoroscopy exposure was of shorter duration in the OA, versus the RA, arm (24.0 minutes vs. 29.4 minutes; P = .005).

On univariate analysis, the lower rate of in-hospital deaths for OA did not reach statistical significance (0% vs. 1.55%; P = .176), but the difference was significant on multivariate-adjusted analysis (P = .034).

There were also higher numerical rates of perforation, tamponade, heart failure, and red blood cell transfusion in the RA group, versus the OA group, but only the latter was significant (P = .002) on multivariate-adjusted analysis.

In contrast, there was a higher rate of MI among those treated with OA, rather than RA (17.1% vs. 13.5%), which was not significant on univariate analysis (P = .573) but did reach significance on adjusted-multivariate analysis (P = .008).

Overall, the authors suggested that both OA and RA are safe procedures, but the mortality reduction suggests a potential relative advantage for OA.

Similar conclusions were reached in the substudy of patients with obesity, called COAP-BMI. In that study, 222 patients were evaluated, of which 91 were treated with OA and 131 were treated with RA.

In-hospital mortality was 0% in the group treated with OA, compared with 3.05% in the group treated with RA (P = .004). The rate of in-hospital major adverse cardiovascular events was also significantly lower in the OA group (15.4% vs. 16.3%; P = .007).

“The rate of secondary outcomes for myocardial infarction and stroke were similar between groups, as were individual procedural safety endpoints, including dissection, perforation, tamponade, or heart failure,” reported Evan Shlofmitz, MD, a cardiology fellow at Northwell Health, Manhasset, N.Y., who collaborated with Dr. Meraj and presented the data at the meeting.

As with the study in the elderly, for which Dr. Shlofmitz was also a coauthor, the study in the obese is the first to compare OA and RA, he noted.

In a third substudy, called COAP-Female, OA and RA were compared in 247 women with CAC who were undergoing PCI.

Again, in-hospital mortality rates were higher in those treated with RA, compared with OA, but the difference was not significant (0.79% vs. 0%; P = .254). There were also no significant differences in any secondary outcomes, including MI, or in any procedural complications, such as rates of dissection, perforation, or major bleeding.

The only significant difference identified in the study was a lower fluoroscopy time in those treated with OA relative to RA (21.3 minutes vs. 27.6 minutes; P = .001).

Although fluoroscopy time was not a primary endpoint, “a reduction in radiation exposure has important ramifications for both patients and operators,” Dr. Shlofmitz noted. He suggested that objective data on outcomes in females is needed, because this group has been “severely underrepresented in atherectomy trials.”

Overall, the substudies reinforce a large body of evidence that atherectomy is safe and effective for achieving revascularization in patients undergoing PCI who have CAC, Dr. Shlofmitz concluded. However, the significant mortality advantage for OA relative to RA in the elderly and the obese suggests that the approaches may not be interchangeable.

Dr. Shlofmitz reported no financial relationships to disclose.

WASHINGTON – Orbital atherectomy (OA) was associated with a lower risk of in-hospital mortality than rotational atherectomy (RA) in female, obese, and elderly study groups, according to data from a prospective observational study.

Each procedure was employed to treat coronary artery calcifications (CAC) in the elderly and the obese prior to percutaneous interventions (PCI).

The data comparing OA with RA in these populations were drawn from the Clinical Outcomes of Atherectomy Prior to PCI (COAP) study, for which Perwaiz M. Meraj, MD, director of structural heart and peripheral vascular disease at the North Shore-LIJ Hospital, Manhasset, N.Y., served as the senior author.

Each set of data, as well as a third set of data comparing OA to RA in female patients, was presented separately at CRT 2017, sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

In the comparison of OA to RA in the elderly, a substudy known as COAP-75, the focus was on patients 75 years of age or older who underwent either OA or RA to remove calcified coronary lesions within the context of PCI. As with the obese and female subgroups, the elderly patients in this study were drawn from 35,590 patients who underwent PCI at one of five tertiary care hospitals in a recent 5-year period.

Of the 310 elderly patients undergoing atherectomy, 117 were treated with OA and 193 with RA. The median lesion lengths and diameters were not significantly different between the two groups. Although OA was less likely to be performed through femoral access (53% vs. 68.9%; P = .005), no other measured differences in procedure were significant, with one exception: Fluoroscopy exposure was of shorter duration in the OA, versus the RA, arm (24.0 minutes vs. 29.4 minutes; P = .005).

On univariate analysis, the lower rate of in-hospital deaths for OA did not reach statistical significance (0% vs. 1.55%; P = .176), but the difference was significant on multivariate-adjusted analysis (P = .034).

There were also higher numerical rates of perforation, tamponade, heart failure, and red blood cell transfusion in the RA group, versus the OA group, but only the latter was significant (P = .002) on multivariate-adjusted analysis.

In contrast, there was a higher rate of MI among those treated with OA, rather than RA (17.1% vs. 13.5%), which was not significant on univariate analysis (P = .573) but did reach significance on adjusted-multivariate analysis (P = .008).

Overall, the authors suggested that both OA and RA are safe procedures, but the mortality reduction suggests a potential relative advantage for OA.

Similar conclusions were reached in the substudy of patients with obesity, called COAP-BMI. In that study, 222 patients were evaluated, of which 91 were treated with OA and 131 were treated with RA.

In-hospital mortality was 0% in the group treated with OA, compared with 3.05% in the group treated with RA (P = .004). The rate of in-hospital major adverse cardiovascular events was also significantly lower in the OA group (15.4% vs. 16.3%; P = .007).

“The rate of secondary outcomes for myocardial infarction and stroke were similar between groups, as were individual procedural safety endpoints, including dissection, perforation, tamponade, or heart failure,” reported Evan Shlofmitz, MD, a cardiology fellow at Northwell Health, Manhasset, N.Y., who collaborated with Dr. Meraj and presented the data at the meeting.

As with the study in the elderly, for which Dr. Shlofmitz was also a coauthor, the study in the obese is the first to compare OA and RA, he noted.

In a third substudy, called COAP-Female, OA and RA were compared in 247 women with CAC who were undergoing PCI.

Again, in-hospital mortality rates were higher in those treated with RA, compared with OA, but the difference was not significant (0.79% vs. 0%; P = .254). There were also no significant differences in any secondary outcomes, including MI, or in any procedural complications, such as rates of dissection, perforation, or major bleeding.

The only significant difference identified in the study was a lower fluoroscopy time in those treated with OA relative to RA (21.3 minutes vs. 27.6 minutes; P = .001).

Although fluoroscopy time was not a primary endpoint, “a reduction in radiation exposure has important ramifications for both patients and operators,” Dr. Shlofmitz noted. He suggested that objective data on outcomes in females is needed, because this group has been “severely underrepresented in atherectomy trials.”

Overall, the substudies reinforce a large body of evidence that atherectomy is safe and effective for achieving revascularization in patients undergoing PCI who have CAC, Dr. Shlofmitz concluded. However, the significant mortality advantage for OA relative to RA in the elderly and the obese suggests that the approaches may not be interchangeable.

Dr. Shlofmitz reported no financial relationships to disclose.

WASHINGTON – Orbital atherectomy (OA) was associated with a lower risk of in-hospital mortality than rotational atherectomy (RA) in female, obese, and elderly study groups, according to data from a prospective observational study.

Each procedure was employed to treat coronary artery calcifications (CAC) in the elderly and the obese prior to percutaneous interventions (PCI).

The data comparing OA with RA in these populations were drawn from the Clinical Outcomes of Atherectomy Prior to PCI (COAP) study, for which Perwaiz M. Meraj, MD, director of structural heart and peripheral vascular disease at the North Shore-LIJ Hospital, Manhasset, N.Y., served as the senior author.

Each set of data, as well as a third set of data comparing OA to RA in female patients, was presented separately at CRT 2017, sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

In the comparison of OA to RA in the elderly, a substudy known as COAP-75, the focus was on patients 75 years of age or older who underwent either OA or RA to remove calcified coronary lesions within the context of PCI. As with the obese and female subgroups, the elderly patients in this study were drawn from 35,590 patients who underwent PCI at one of five tertiary care hospitals in a recent 5-year period.

Of the 310 elderly patients undergoing atherectomy, 117 were treated with OA and 193 with RA. The median lesion lengths and diameters were not significantly different between the two groups. Although OA was less likely to be performed through femoral access (53% vs. 68.9%; P = .005), no other measured differences in procedure were significant, with one exception: Fluoroscopy exposure was of shorter duration in the OA, versus the RA, arm (24.0 minutes vs. 29.4 minutes; P = .005).

On univariate analysis, the lower rate of in-hospital deaths for OA did not reach statistical significance (0% vs. 1.55%; P = .176), but the difference was significant on multivariate-adjusted analysis (P = .034).

There were also higher numerical rates of perforation, tamponade, heart failure, and red blood cell transfusion in the RA group, versus the OA group, but only the latter was significant (P = .002) on multivariate-adjusted analysis.

In contrast, there was a higher rate of MI among those treated with OA, rather than RA (17.1% vs. 13.5%), which was not significant on univariate analysis (P = .573) but did reach significance on adjusted-multivariate analysis (P = .008).

Overall, the authors suggested that both OA and RA are safe procedures, but the mortality reduction suggests a potential relative advantage for OA.

Similar conclusions were reached in the substudy of patients with obesity, called COAP-BMI. In that study, 222 patients were evaluated, of which 91 were treated with OA and 131 were treated with RA.

In-hospital mortality was 0% in the group treated with OA, compared with 3.05% in the group treated with RA (P = .004). The rate of in-hospital major adverse cardiovascular events was also significantly lower in the OA group (15.4% vs. 16.3%; P = .007).

“The rate of secondary outcomes for myocardial infarction and stroke were similar between groups, as were individual procedural safety endpoints, including dissection, perforation, tamponade, or heart failure,” reported Evan Shlofmitz, MD, a cardiology fellow at Northwell Health, Manhasset, N.Y., who collaborated with Dr. Meraj and presented the data at the meeting.

As with the study in the elderly, for which Dr. Shlofmitz was also a coauthor, the study in the obese is the first to compare OA and RA, he noted.

In a third substudy, called COAP-Female, OA and RA were compared in 247 women with CAC who were undergoing PCI.

Again, in-hospital mortality rates were higher in those treated with RA, compared with OA, but the difference was not significant (0.79% vs. 0%; P = .254). There were also no significant differences in any secondary outcomes, including MI, or in any procedural complications, such as rates of dissection, perforation, or major bleeding.

The only significant difference identified in the study was a lower fluoroscopy time in those treated with OA relative to RA (21.3 minutes vs. 27.6 minutes; P = .001).

Although fluoroscopy time was not a primary endpoint, “a reduction in radiation exposure has important ramifications for both patients and operators,” Dr. Shlofmitz noted. He suggested that objective data on outcomes in females is needed, because this group has been “severely underrepresented in atherectomy trials.”

Overall, the substudies reinforce a large body of evidence that atherectomy is safe and effective for achieving revascularization in patients undergoing PCI who have CAC, Dr. Shlofmitz concluded. However, the significant mortality advantage for OA relative to RA in the elderly and the obese suggests that the approaches may not be interchangeable.

Dr. Shlofmitz reported no financial relationships to disclose.

At 12 weeks, 77% of psoriasis patients treated with risankizumab showed a 90% or greater reduction in Psoriasis Area and Severity Index (PASI) score, compared with 40% of ustekinumab patients, in a phase II randomized trial.

The results were published April 19 in the New England Journal of Medicine.

Ustekinumab (Stelara), approved by the Food and Drug Administration in 2009, blocks interleukin-12 and interleukin-23 and has demonstrated effectiveness in psoriasis patients. However, the humanized IgG1 monoclonal antibody risankizumab goes farther and “selectively inhibits interleukin-23 by specifically targeting p19,” wrote Kim A. Papp, MD, PhD, of K. Papp Clinical Research and Probity Medical Research, Waterloo, Ont., and associates (N. Engl. J. Med. 2017;376:1551-60. doi: 10.1056/NEJMoa1607017).

To compare clinical response and safety, the researchers enrolled 166 adults aged 18-75 years with moderate to severe plaque psoriasis, in the phase II study. Patients were randomized to subcutaneous injections of risankizumab at one of three doses, or ustekinumab at one of two doses. Risankizumab patients received a single 18-mg dose at week 0, or 90-mg or 180-mg doses at weeks 0, 4, and 16. Ustekinumab patients weighing 100 kg or less received 45 mg at weeks 0, 4, and 16; those weighing more than 100 kg received 90 mg at weeks 0, 4, and 16. Demographics were similar among the treatment groups.

The primary end point was a 90% or greater reduction in the PASI score at week 12, compared with baseline.

In pooled results of the risankizumab 90-mg and 180-mg groups, 77% of patients achieved a PASI 90 at 12 weeks (73% of the 90-mg group and 81% of the 180-mg group), vs. 40% of ustekinumab patients (P less than .001). Complete clearance of lesions (PASI 100) occurred among risankizumab patients in 14% of the 18-mg group, 41% of the 90-mg group, and 48% of the 180-mg group, compared with 18% of the ustekinumab group.

Among risankizumab patients, the rates of adverse events through 48 weeks were 81% in the 180-mg group, 80% in the 90-mg group, and 69% in the 180-mg group, compared with 72% in those on ustekinumab, with nasopharyngitis the most commonly reported adverse event in all the treatment groups. The rates of serious adverse events were 12% and 15% among those in the 18-mg and 90-mg risankizumab groups, respectively; 0% among those on the 180-mg dose, and 8% among those on ustekinumab.

The study was not large or long enough to provide conclusive safety data on risankizumab, and additional studies are needed to review psoriasis lesions over a longer time period and include both placebo and active comparators, researchers noted. However, the results suggest that “the selective blockade of interleukin-23 through the inhibition of the p19 subunit rather than p40 provides a more complete inhibition of interleukin-23 activity, potentially resulting in a greater efficacy in the treatment of plaque psoriasis at the doses used,” they said.

The study was supported by Boehringer Ingelheim. Several study coauthors, including lead author Dr. Papp, disclosed relationships with Boehringer Ingelheim and other companies. Several authors are Boehringer Ingelheim employees.
 

[email protected]

At 12 weeks, 77% of psoriasis patients treated with risankizumab showed a 90% or greater reduction in Psoriasis Area and Severity Index (PASI) score, compared with 40% of ustekinumab patients, in a phase II randomized trial.

The results were published April 19 in the New England Journal of Medicine.

Ustekinumab (Stelara), approved by the Food and Drug Administration in 2009, blocks interleukin-12 and interleukin-23 and has demonstrated effectiveness in psoriasis patients. However, the humanized IgG1 monoclonal antibody risankizumab goes farther and “selectively inhibits interleukin-23 by specifically targeting p19,” wrote Kim A. Papp, MD, PhD, of K. Papp Clinical Research and Probity Medical Research, Waterloo, Ont., and associates (N. Engl. J. Med. 2017;376:1551-60. doi: 10.1056/NEJMoa1607017).

To compare clinical response and safety, the researchers enrolled 166 adults aged 18-75 years with moderate to severe plaque psoriasis, in the phase II study. Patients were randomized to subcutaneous injections of risankizumab at one of three doses, or ustekinumab at one of two doses. Risankizumab patients received a single 18-mg dose at week 0, or 90-mg or 180-mg doses at weeks 0, 4, and 16. Ustekinumab patients weighing 100 kg or less received 45 mg at weeks 0, 4, and 16; those weighing more than 100 kg received 90 mg at weeks 0, 4, and 16. Demographics were similar among the treatment groups.

The primary end point was a 90% or greater reduction in the PASI score at week 12, compared with baseline.

In pooled results of the risankizumab 90-mg and 180-mg groups, 77% of patients achieved a PASI 90 at 12 weeks (73% of the 90-mg group and 81% of the 180-mg group), vs. 40% of ustekinumab patients (P less than .001). Complete clearance of lesions (PASI 100) occurred among risankizumab patients in 14% of the 18-mg group, 41% of the 90-mg group, and 48% of the 180-mg group, compared with 18% of the ustekinumab group.

Among risankizumab patients, the rates of adverse events through 48 weeks were 81% in the 180-mg group, 80% in the 90-mg group, and 69% in the 180-mg group, compared with 72% in those on ustekinumab, with nasopharyngitis the most commonly reported adverse event in all the treatment groups. The rates of serious adverse events were 12% and 15% among those in the 18-mg and 90-mg risankizumab groups, respectively; 0% among those on the 180-mg dose, and 8% among those on ustekinumab.

The study was not large or long enough to provide conclusive safety data on risankizumab, and additional studies are needed to review psoriasis lesions over a longer time period and include both placebo and active comparators, researchers noted. However, the results suggest that “the selective blockade of interleukin-23 through the inhibition of the p19 subunit rather than p40 provides a more complete inhibition of interleukin-23 activity, potentially resulting in a greater efficacy in the treatment of plaque psoriasis at the doses used,” they said.

The study was supported by Boehringer Ingelheim. Several study coauthors, including lead author Dr. Papp, disclosed relationships with Boehringer Ingelheim and other companies. Several authors are Boehringer Ingelheim employees.
 

[email protected]

At 12 weeks, 77% of psoriasis patients treated with risankizumab showed a 90% or greater reduction in Psoriasis Area and Severity Index (PASI) score, compared with 40% of ustekinumab patients, in a phase II randomized trial.

The results were published April 19 in the New England Journal of Medicine.

Ustekinumab (Stelara), approved by the Food and Drug Administration in 2009, blocks interleukin-12 and interleukin-23 and has demonstrated effectiveness in psoriasis patients. However, the humanized IgG1 monoclonal antibody risankizumab goes farther and “selectively inhibits interleukin-23 by specifically targeting p19,” wrote Kim A. Papp, MD, PhD, of K. Papp Clinical Research and Probity Medical Research, Waterloo, Ont., and associates (N. Engl. J. Med. 2017;376:1551-60. doi: 10.1056/NEJMoa1607017).

To compare clinical response and safety, the researchers enrolled 166 adults aged 18-75 years with moderate to severe plaque psoriasis, in the phase II study. Patients were randomized to subcutaneous injections of risankizumab at one of three doses, or ustekinumab at one of two doses. Risankizumab patients received a single 18-mg dose at week 0, or 90-mg or 180-mg doses at weeks 0, 4, and 16. Ustekinumab patients weighing 100 kg or less received 45 mg at weeks 0, 4, and 16; those weighing more than 100 kg received 90 mg at weeks 0, 4, and 16. Demographics were similar among the treatment groups.

The primary end point was a 90% or greater reduction in the PASI score at week 12, compared with baseline.

In pooled results of the risankizumab 90-mg and 180-mg groups, 77% of patients achieved a PASI 90 at 12 weeks (73% of the 90-mg group and 81% of the 180-mg group), vs. 40% of ustekinumab patients (P less than .001). Complete clearance of lesions (PASI 100) occurred among risankizumab patients in 14% of the 18-mg group, 41% of the 90-mg group, and 48% of the 180-mg group, compared with 18% of the ustekinumab group.

Among risankizumab patients, the rates of adverse events through 48 weeks were 81% in the 180-mg group, 80% in the 90-mg group, and 69% in the 180-mg group, compared with 72% in those on ustekinumab, with nasopharyngitis the most commonly reported adverse event in all the treatment groups. The rates of serious adverse events were 12% and 15% among those in the 18-mg and 90-mg risankizumab groups, respectively; 0% among those on the 180-mg dose, and 8% among those on ustekinumab.

The study was not large or long enough to provide conclusive safety data on risankizumab, and additional studies are needed to review psoriasis lesions over a longer time period and include both placebo and active comparators, researchers noted. However, the results suggest that “the selective blockade of interleukin-23 through the inhibition of the p19 subunit rather than p40 provides a more complete inhibition of interleukin-23 activity, potentially resulting in a greater efficacy in the treatment of plaque psoriasis at the doses used,” they said.

The study was supported by Boehringer Ingelheim. Several study coauthors, including lead author Dr. Papp, disclosed relationships with Boehringer Ingelheim and other companies. Several authors are Boehringer Ingelheim employees.
 

[email protected]

Histopathology findings of cytologic atypia, architectural disorder, and pagetoid spread are common in congenital melanocytic nevi (CMN) of all sizes in children aged 0-35 months, and tend to have benign outcomes, according to a retrospective study.

Emily A. Simons, MPH, and her associates at Boston Children’s Hospital studied 197 nevi in 179 patients with an average age of 14 months (range, 4 days to 35 months); 51% were female. Of those, 80% had skin types I-II, and 90% were white. The majority of the lesions involved the head or trunk and were predominantly medium in size, and 58% had a projected adult size of 1.5-10 cm. The study was retrospective; cases had been diagnosed between 1993 and 2013.

Cytologic atypia, architectural disorder, and pagetoid spread were the most frequent features – they were present in 73% of nevi and were closely associated. Combined histologic patterns of a blue nevus, spindle and Spitz nevus, or a deep penetrating nevus were identified in 40% of CMN. Proliferative nodules occurred in 5% of nevi.

Clinical outcomes were available for 130 patients, including 26 with large CMN and 8 with proliferative nodules. The children were alive and had not been diagnosed with melanoma at a mean follow-up of a mean of 8.4 years (range, 7 months to 21.3 years), even though margins of the last excision were positive in 41% of all CMN and in 77% of large CMN.

Malignant transformation of CMN certainly should be recognized, but the morbidity of overdiagnosis also needs to be considered. “Excision of larger CMN might require serial excisions under general anesthesia, the use of tissue expanders, and grafts,” Dr. Simons and her associates said.

Among the limitations of this study were that the majority of patients were white, so the results may not translate to children with darker skin types, they noted.

“The diagnosis of malignant melanoma should be made with great caution in this population,” they concluded, pointing out that the histopathologic features alone (cytologic atypia, architectural disorder, and pagetoid spread) “should not be interpreted as evidence for potential malignant behavior or serve as grounds for further excision.”

Read more in the Journal of the American Academy of Dermatology (2017 May;76[5]941-7).

The authors had no relevant financial disorders.

Histopathology findings of cytologic atypia, architectural disorder, and pagetoid spread are common in congenital melanocytic nevi (CMN) of all sizes in children aged 0-35 months, and tend to have benign outcomes, according to a retrospective study.

Emily A. Simons, MPH, and her associates at Boston Children’s Hospital studied 197 nevi in 179 patients with an average age of 14 months (range, 4 days to 35 months); 51% were female. Of those, 80% had skin types I-II, and 90% were white. The majority of the lesions involved the head or trunk and were predominantly medium in size, and 58% had a projected adult size of 1.5-10 cm. The study was retrospective; cases had been diagnosed between 1993 and 2013.

Cytologic atypia, architectural disorder, and pagetoid spread were the most frequent features – they were present in 73% of nevi and were closely associated. Combined histologic patterns of a blue nevus, spindle and Spitz nevus, or a deep penetrating nevus were identified in 40% of CMN. Proliferative nodules occurred in 5% of nevi.

Clinical outcomes were available for 130 patients, including 26 with large CMN and 8 with proliferative nodules. The children were alive and had not been diagnosed with melanoma at a mean follow-up of a mean of 8.4 years (range, 7 months to 21.3 years), even though margins of the last excision were positive in 41% of all CMN and in 77% of large CMN.

Malignant transformation of CMN certainly should be recognized, but the morbidity of overdiagnosis also needs to be considered. “Excision of larger CMN might require serial excisions under general anesthesia, the use of tissue expanders, and grafts,” Dr. Simons and her associates said.

Among the limitations of this study were that the majority of patients were white, so the results may not translate to children with darker skin types, they noted.

“The diagnosis of malignant melanoma should be made with great caution in this population,” they concluded, pointing out that the histopathologic features alone (cytologic atypia, architectural disorder, and pagetoid spread) “should not be interpreted as evidence for potential malignant behavior or serve as grounds for further excision.”

Read more in the Journal of the American Academy of Dermatology (2017 May;76[5]941-7).

The authors had no relevant financial disorders.

Histopathology findings of cytologic atypia, architectural disorder, and pagetoid spread are common in congenital melanocytic nevi (CMN) of all sizes in children aged 0-35 months, and tend to have benign outcomes, according to a retrospective study.

Emily A. Simons, MPH, and her associates at Boston Children’s Hospital studied 197 nevi in 179 patients with an average age of 14 months (range, 4 days to 35 months); 51% were female. Of those, 80% had skin types I-II, and 90% were white. The majority of the lesions involved the head or trunk and were predominantly medium in size, and 58% had a projected adult size of 1.5-10 cm. The study was retrospective; cases had been diagnosed between 1993 and 2013.

Cytologic atypia, architectural disorder, and pagetoid spread were the most frequent features – they were present in 73% of nevi and were closely associated. Combined histologic patterns of a blue nevus, spindle and Spitz nevus, or a deep penetrating nevus were identified in 40% of CMN. Proliferative nodules occurred in 5% of nevi.

Clinical outcomes were available for 130 patients, including 26 with large CMN and 8 with proliferative nodules. The children were alive and had not been diagnosed with melanoma at a mean follow-up of a mean of 8.4 years (range, 7 months to 21.3 years), even though margins of the last excision were positive in 41% of all CMN and in 77% of large CMN.

Malignant transformation of CMN certainly should be recognized, but the morbidity of overdiagnosis also needs to be considered. “Excision of larger CMN might require serial excisions under general anesthesia, the use of tissue expanders, and grafts,” Dr. Simons and her associates said.

Among the limitations of this study were that the majority of patients were white, so the results may not translate to children with darker skin types, they noted.

“The diagnosis of malignant melanoma should be made with great caution in this population,” they concluded, pointing out that the histopathologic features alone (cytologic atypia, architectural disorder, and pagetoid spread) “should not be interpreted as evidence for potential malignant behavior or serve as grounds for further excision.”

Read more in the Journal of the American Academy of Dermatology (2017 May;76[5]941-7).

The authors had no relevant financial disorders.

An increase in spike frequency does not help clinicians predict the outcome of surgery in patients with temporal lobe epilepsy. To reach that conclusion, researchers used scalp video monitoring data from patients who had anterior temporal lobe epilepsy to look for interictal epileptiform abnormalities, comparing patients with more than 60 spikes/hour to those with fewer spikes. They found no significant differences in seizure outcomes among patients who had undergone anterior temporal lobectomy.

Ngo L, Sperling MR, Skidmore C, Mintzer S, Nei M. Absolute spike frequency as a predictor of surgical outcome in temporal lobe epilepsy. Seizure. 2017;47:83-86.

An increase in spike frequency does not help clinicians predict the outcome of surgery in patients with temporal lobe epilepsy. To reach that conclusion, researchers used scalp video monitoring data from patients who had anterior temporal lobe epilepsy to look for interictal epileptiform abnormalities, comparing patients with more than 60 spikes/hour to those with fewer spikes. They found no significant differences in seizure outcomes among patients who had undergone anterior temporal lobectomy.

Ngo L, Sperling MR, Skidmore C, Mintzer S, Nei M. Absolute spike frequency as a predictor of surgical outcome in temporal lobe epilepsy. Seizure. 2017;47:83-86.

An increase in spike frequency does not help clinicians predict the outcome of surgery in patients with temporal lobe epilepsy. To reach that conclusion, researchers used scalp video monitoring data from patients who had anterior temporal lobe epilepsy to look for interictal epileptiform abnormalities, comparing patients with more than 60 spikes/hour to those with fewer spikes. They found no significant differences in seizure outcomes among patients who had undergone anterior temporal lobectomy.

Ngo L, Sperling MR, Skidmore C, Mintzer S, Nei M. Absolute spike frequency as a predictor of surgical outcome in temporal lobe epilepsy. Seizure. 2017;47:83-86.

Patients with refractory focal epilepsy seem to have older brains, suggests a study that used whole brain T1-weighted MRI scans to estimate the predicted brain age versus chronological age. On average, the difference between predicted brain age and chronological age in patients with refractory focal epilepsy was 4.5 years greater than the researchers observed in healthy adults. The researchers also found that an earlier onset of refractory focal epilepsy was linked to increased brain age.

Pardoe H, Cole JH, Blackmon K ,et al. Structural brain changes in medically refractory focal epilepsy resemble premature brain aging. Epilepsy Res. 2017;133:28-32.

Patients with refractory focal epilepsy seem to have older brains, suggests a study that used whole brain T1-weighted MRI scans to estimate the predicted brain age versus chronological age. On average, the difference between predicted brain age and chronological age in patients with refractory focal epilepsy was 4.5 years greater than the researchers observed in healthy adults. The researchers also found that an earlier onset of refractory focal epilepsy was linked to increased brain age.

Pardoe H, Cole JH, Blackmon K ,et al. Structural brain changes in medically refractory focal epilepsy resemble premature brain aging. Epilepsy Res. 2017;133:28-32.

Patients with refractory focal epilepsy seem to have older brains, suggests a study that used whole brain T1-weighted MRI scans to estimate the predicted brain age versus chronological age. On average, the difference between predicted brain age and chronological age in patients with refractory focal epilepsy was 4.5 years greater than the researchers observed in healthy adults. The researchers also found that an earlier onset of refractory focal epilepsy was linked to increased brain age.

Pardoe H, Cole JH, Blackmon K ,et al. Structural brain changes in medically refractory focal epilepsy resemble premature brain aging. Epilepsy Res. 2017;133:28-32.