Pazopanib can be considered as a first line alternative treatment to doxorubicin in patients over age 60 with advanced, inoperable soft tissue sarcomas, based on the results of the phase 2 EPAZ study presented at the annual meeting of the American Society of Clinical Oncology.

Pazopanib outcomes compared to those with doxorubicin in the study; but unlike doxorubicin, pazopanib was not associated with neutropenia, reported Viktor Grünwald, MD, of the Medical School Hanover, Germany. “The distinct AE (adverse event) profile may be used to council patients and tailor therapy to individual needs.”

In the randomized study with a median 12-month follow up of previously untreated patients with a median age of 71 years, the incidence of grade 4 neutropenia and neutropenic fever were 56% and 10% for 39 patients given doxorubicin and 0% and 0% for 81 patients given pazopanib, respectively. Overall survival was 14.3 months and 12.3 months, a nonsignificant difference. The most frequent adverse events for doxorubicin were fatigue (64.9%), alopecia (56.8%) and nausea (48.6%), and for pazopanib they were fatigue (58%), nausea (43.2%) and diarrhea (43.2%). Similar outcomes were reported for global EORTC QLQ-C30 measures.

EPAZ included patients aged 60 years and older (median 71 years) with no prior systemic treatment for soft tissue sarcoma, progressive disease, ECOG 0-2, and adequate organ function. After 1:2 randomization, patients received either doxorubicin 75 mg/m² every 3 weeks for a total of 6 cycles or oral pazopanib 800 mg/day given continuously. ECOG 2 and liposarcoma histology were used for stratification.

Dr. Grunwald and several of his co-authors disclosed financial relationships with various drug companies including Novartis, the maker of pazopanib (Votrient). Clinical trial information: NCT01861951
 

SOURCE: Grunwald V et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11506.

Pazopanib can be considered as a first line alternative treatment to doxorubicin in patients over age 60 with advanced, inoperable soft tissue sarcomas, based on the results of the phase 2 EPAZ study presented at the annual meeting of the American Society of Clinical Oncology.

Pazopanib outcomes compared to those with doxorubicin in the study; but unlike doxorubicin, pazopanib was not associated with neutropenia, reported Viktor Grünwald, MD, of the Medical School Hanover, Germany. “The distinct AE (adverse event) profile may be used to council patients and tailor therapy to individual needs.”

In the randomized study with a median 12-month follow up of previously untreated patients with a median age of 71 years, the incidence of grade 4 neutropenia and neutropenic fever were 56% and 10% for 39 patients given doxorubicin and 0% and 0% for 81 patients given pazopanib, respectively. Overall survival was 14.3 months and 12.3 months, a nonsignificant difference. The most frequent adverse events for doxorubicin were fatigue (64.9%), alopecia (56.8%) and nausea (48.6%), and for pazopanib they were fatigue (58%), nausea (43.2%) and diarrhea (43.2%). Similar outcomes were reported for global EORTC QLQ-C30 measures.

EPAZ included patients aged 60 years and older (median 71 years) with no prior systemic treatment for soft tissue sarcoma, progressive disease, ECOG 0-2, and adequate organ function. After 1:2 randomization, patients received either doxorubicin 75 mg/m² every 3 weeks for a total of 6 cycles or oral pazopanib 800 mg/day given continuously. ECOG 2 and liposarcoma histology were used for stratification.

Dr. Grunwald and several of his co-authors disclosed financial relationships with various drug companies including Novartis, the maker of pazopanib (Votrient). Clinical trial information: NCT01861951
 

SOURCE: Grunwald V et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11506.

Pazopanib can be considered as a first line alternative treatment to doxorubicin in patients over age 60 with advanced, inoperable soft tissue sarcomas, based on the results of the phase 2 EPAZ study presented at the annual meeting of the American Society of Clinical Oncology.

Pazopanib outcomes compared to those with doxorubicin in the study; but unlike doxorubicin, pazopanib was not associated with neutropenia, reported Viktor Grünwald, MD, of the Medical School Hanover, Germany. “The distinct AE (adverse event) profile may be used to council patients and tailor therapy to individual needs.”

In the randomized study with a median 12-month follow up of previously untreated patients with a median age of 71 years, the incidence of grade 4 neutropenia and neutropenic fever were 56% and 10% for 39 patients given doxorubicin and 0% and 0% for 81 patients given pazopanib, respectively. Overall survival was 14.3 months and 12.3 months, a nonsignificant difference. The most frequent adverse events for doxorubicin were fatigue (64.9%), alopecia (56.8%) and nausea (48.6%), and for pazopanib they were fatigue (58%), nausea (43.2%) and diarrhea (43.2%). Similar outcomes were reported for global EORTC QLQ-C30 measures.

EPAZ included patients aged 60 years and older (median 71 years) with no prior systemic treatment for soft tissue sarcoma, progressive disease, ECOG 0-2, and adequate organ function. After 1:2 randomization, patients received either doxorubicin 75 mg/m² every 3 weeks for a total of 6 cycles or oral pazopanib 800 mg/day given continuously. ECOG 2 and liposarcoma histology were used for stratification.

Dr. Grunwald and several of his co-authors disclosed financial relationships with various drug companies including Novartis, the maker of pazopanib (Votrient). Clinical trial information: NCT01861951
 

SOURCE: Grunwald V et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11506.

Pexidartinib significantly improved overall response rates and functioning in patients with advanced tenosynovial giant cell tumors (TGCT), based on the final results of the ENLIVEN study, presented at the annual meeting of the American Society of Clinical Oncology in Chicago.

“Pexidartinib, a novel CSF1 receptor inhibitor, may offer a relevant treatment option for patients with TGCT, which is associated with severe morbidity or functional limitations, and for which surgery is not recommended,” said William Tap, MD, of Memorial Sloan Kettering Cancer Center, New York.

Compared with placebo in patients with advanced, symptomatic TGCT, pexidartinib significantly improved overall response rates; RECIST was 39% with pexidartinib and 0% with placebo. Tumor volume score improvement was 56% with pexidartinib and 0% with placebo. Both results were significant at P less than 0.0001.

“Importantly, these responses correlated with improved patient symptoms and function,” Dr. Tap said. “Pexidartinib was generally well tolerated with serious, nonfatal liver toxicity with increased bilirubin in 4% of patients.” The majority of other adverse events with pexidartinib (hair color changes, vomiting, fatigue, dysgeusia, and periorbital edema) were less than grade 3.

The primary treatment for these patients is surgery; there are currently no approved systemic therapies for advanced tenosynovial giant cell tumor. In previous studies by others, imatinib, evaluated in 27 patients, was associated with a 19% overall response rate (ORR). Nilotinib, evaluated in 51 patients, was associated with a 0% ORR at week 12.

ENLIVEN is a double-blind, randomized, placebo-controlled international, phase 3 study whose participants had histologically confirmed, advanced, symptomatic TGCT of greater than 2 cm. Several had previous surgeries, but further surgical resection would have been associated with the potential for worsening functional limitations or severe morbidity.

In ENLIVEN, 61 patients were randomized to pexidartinib and 59 to placebo. All had recurrent or inoperable TGCT. Patients received placebo or pexidartinib 1000 mg/day (split, BID for 2 weeks) then 800 mg/day (split BID for 22 weeks).

Nine patients in the active treatment group and 11 in the placebo group discontinued therapy. Eight patients discontinued pexidartinib due to hepatic adverse events; all serious hepatic events appeared in the first 2 months of treatment.

At 25 weeks, blinded reviews of MRI scans were performed. A partial response was seen in 12 (52%) patients and stable disease was seen in 7 (30%), based on RECIST 1.1.

Also at week 25, pexidartinib-treated patients did better on scores of functional endpoints related to range of motion, PROMIS physical function, stiffness, and BPI worst pain response. Based on functional endpoints, 9 of 61 (15%) had a complete response and 15 (25%) had a partial response, for an overall response rate of 24 (39%); P less than 0.0001.

None of the 59 patients in the placebo group had a response.

Tumor volume scores at week 25 were complete in 3 (5%) and partial in 31 (51%); overall response rate was 34 (56%); P less than 0.0001. Disease was stable in 14 (23%), progressive in 1 (2%), and not evaluable in 12 (20%). There were no complete or partial responses in the placebo group; disease was stable in 45 (76%), progressive in 2 (3%), and not evaluable in 12 (20%).

Dr. Tap disclosed consulting or advisory roles with Daiichi Sankyo, the maker of pexidartinib; as well as Adaptimmune; Blueprint Medicines; Eisai; EMD Serono; Immune Design; Janssen; Lilly; Loxo; Novartis; Plexxikon; TRACON Pharma. Clinical trial information: NCT02371369.

SOURCE: Tap W et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11502.

Pexidartinib significantly improved overall response rates and functioning in patients with advanced tenosynovial giant cell tumors (TGCT), based on the final results of the ENLIVEN study, presented at the annual meeting of the American Society of Clinical Oncology in Chicago.

“Pexidartinib, a novel CSF1 receptor inhibitor, may offer a relevant treatment option for patients with TGCT, which is associated with severe morbidity or functional limitations, and for which surgery is not recommended,” said William Tap, MD, of Memorial Sloan Kettering Cancer Center, New York.

Compared with placebo in patients with advanced, symptomatic TGCT, pexidartinib significantly improved overall response rates; RECIST was 39% with pexidartinib and 0% with placebo. Tumor volume score improvement was 56% with pexidartinib and 0% with placebo. Both results were significant at P less than 0.0001.

“Importantly, these responses correlated with improved patient symptoms and function,” Dr. Tap said. “Pexidartinib was generally well tolerated with serious, nonfatal liver toxicity with increased bilirubin in 4% of patients.” The majority of other adverse events with pexidartinib (hair color changes, vomiting, fatigue, dysgeusia, and periorbital edema) were less than grade 3.

The primary treatment for these patients is surgery; there are currently no approved systemic therapies for advanced tenosynovial giant cell tumor. In previous studies by others, imatinib, evaluated in 27 patients, was associated with a 19% overall response rate (ORR). Nilotinib, evaluated in 51 patients, was associated with a 0% ORR at week 12.

ENLIVEN is a double-blind, randomized, placebo-controlled international, phase 3 study whose participants had histologically confirmed, advanced, symptomatic TGCT of greater than 2 cm. Several had previous surgeries, but further surgical resection would have been associated with the potential for worsening functional limitations or severe morbidity.

In ENLIVEN, 61 patients were randomized to pexidartinib and 59 to placebo. All had recurrent or inoperable TGCT. Patients received placebo or pexidartinib 1000 mg/day (split, BID for 2 weeks) then 800 mg/day (split BID for 22 weeks).

Nine patients in the active treatment group and 11 in the placebo group discontinued therapy. Eight patients discontinued pexidartinib due to hepatic adverse events; all serious hepatic events appeared in the first 2 months of treatment.

At 25 weeks, blinded reviews of MRI scans were performed. A partial response was seen in 12 (52%) patients and stable disease was seen in 7 (30%), based on RECIST 1.1.

Also at week 25, pexidartinib-treated patients did better on scores of functional endpoints related to range of motion, PROMIS physical function, stiffness, and BPI worst pain response. Based on functional endpoints, 9 of 61 (15%) had a complete response and 15 (25%) had a partial response, for an overall response rate of 24 (39%); P less than 0.0001.

None of the 59 patients in the placebo group had a response.

Tumor volume scores at week 25 were complete in 3 (5%) and partial in 31 (51%); overall response rate was 34 (56%); P less than 0.0001. Disease was stable in 14 (23%), progressive in 1 (2%), and not evaluable in 12 (20%). There were no complete or partial responses in the placebo group; disease was stable in 45 (76%), progressive in 2 (3%), and not evaluable in 12 (20%).

Dr. Tap disclosed consulting or advisory roles with Daiichi Sankyo, the maker of pexidartinib; as well as Adaptimmune; Blueprint Medicines; Eisai; EMD Serono; Immune Design; Janssen; Lilly; Loxo; Novartis; Plexxikon; TRACON Pharma. Clinical trial information: NCT02371369.

SOURCE: Tap W et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11502.

Pexidartinib significantly improved overall response rates and functioning in patients with advanced tenosynovial giant cell tumors (TGCT), based on the final results of the ENLIVEN study, presented at the annual meeting of the American Society of Clinical Oncology in Chicago.

“Pexidartinib, a novel CSF1 receptor inhibitor, may offer a relevant treatment option for patients with TGCT, which is associated with severe morbidity or functional limitations, and for which surgery is not recommended,” said William Tap, MD, of Memorial Sloan Kettering Cancer Center, New York.

Compared with placebo in patients with advanced, symptomatic TGCT, pexidartinib significantly improved overall response rates; RECIST was 39% with pexidartinib and 0% with placebo. Tumor volume score improvement was 56% with pexidartinib and 0% with placebo. Both results were significant at P less than 0.0001.

“Importantly, these responses correlated with improved patient symptoms and function,” Dr. Tap said. “Pexidartinib was generally well tolerated with serious, nonfatal liver toxicity with increased bilirubin in 4% of patients.” The majority of other adverse events with pexidartinib (hair color changes, vomiting, fatigue, dysgeusia, and periorbital edema) were less than grade 3.

The primary treatment for these patients is surgery; there are currently no approved systemic therapies for advanced tenosynovial giant cell tumor. In previous studies by others, imatinib, evaluated in 27 patients, was associated with a 19% overall response rate (ORR). Nilotinib, evaluated in 51 patients, was associated with a 0% ORR at week 12.

ENLIVEN is a double-blind, randomized, placebo-controlled international, phase 3 study whose participants had histologically confirmed, advanced, symptomatic TGCT of greater than 2 cm. Several had previous surgeries, but further surgical resection would have been associated with the potential for worsening functional limitations or severe morbidity.

In ENLIVEN, 61 patients were randomized to pexidartinib and 59 to placebo. All had recurrent or inoperable TGCT. Patients received placebo or pexidartinib 1000 mg/day (split, BID for 2 weeks) then 800 mg/day (split BID for 22 weeks).

Nine patients in the active treatment group and 11 in the placebo group discontinued therapy. Eight patients discontinued pexidartinib due to hepatic adverse events; all serious hepatic events appeared in the first 2 months of treatment.

At 25 weeks, blinded reviews of MRI scans were performed. A partial response was seen in 12 (52%) patients and stable disease was seen in 7 (30%), based on RECIST 1.1.

Also at week 25, pexidartinib-treated patients did better on scores of functional endpoints related to range of motion, PROMIS physical function, stiffness, and BPI worst pain response. Based on functional endpoints, 9 of 61 (15%) had a complete response and 15 (25%) had a partial response, for an overall response rate of 24 (39%); P less than 0.0001.

None of the 59 patients in the placebo group had a response.

Tumor volume scores at week 25 were complete in 3 (5%) and partial in 31 (51%); overall response rate was 34 (56%); P less than 0.0001. Disease was stable in 14 (23%), progressive in 1 (2%), and not evaluable in 12 (20%). There were no complete or partial responses in the placebo group; disease was stable in 45 (76%), progressive in 2 (3%), and not evaluable in 12 (20%).

Dr. Tap disclosed consulting or advisory roles with Daiichi Sankyo, the maker of pexidartinib; as well as Adaptimmune; Blueprint Medicines; Eisai; EMD Serono; Immune Design; Janssen; Lilly; Loxo; Novartis; Plexxikon; TRACON Pharma. Clinical trial information: NCT02371369.

SOURCE: Tap W et al. ASCO 2018 (annual meeting of the American Society of Clinical Oncology), Abstract 11502.

PARIS – The Amplatzer Amulet left atrial appendage occlusion device reduced stroke risk by nearly 60% at 1 year in a large, real-world registry of patients with atrial fibrillation at dual high risk for stroke and bleeding, Ulf Landmesser, MD, reported at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

One of the most impressive findings was that this feat was accomplished by and large without background oral anticoagulation. Indeed, 83% of the 1,088 patients in this 61-center, 17-country study had contraindications to oral anticoagulation. Only 11% of subjects were discharged on oral anticoagulation after device implantation, while 22.5% were discharged on aspirin or clopidogrel monotherapy. By 1-3 months post implantation, 60% of patients were either on a single antiplatelet agent or no antithrombotic medication at all.

Bruce Jancin/MDedge News

“Antithrombotic therapy was individualized by the patient’s physician. There didn’t seem to be an increased risk of device-related thrombus in these patients on single antiplatelet therapy. Our data suggest that, given the high bleeding risk, single antiplatelet therapy seems to be a good option for these patients,” said Dr. Landmesser, a professor in and the chair of the department of cardiology at Charité Medical School in Berlin.

Participants in the Global Prospective Amulet Study averaged 75 years of age, and 72% had a history of major bleeding. The average CHA2DS2-VASc score was 4.2, with a HAS-BLED score of 3.3, which emphasizes the high-risk nature of study participants.

On the basis of the CHA2DS2-VASc score, the predicted 1-year ischemic stroke rate without oral anticoagulation was 6.7%, so the actual 2.9% rate represented a 57% reduction in risk. Similarly, for the composite endpoint of ischemic stroke, transient ischemic attack, or systemic embolism, the predicted rate was 9.4%, but the achieved rate was 3.8%, which represented a 60% reduction in risk.

The annualized major bleeding rate was 10.3% despite the low usage of oral anticoagulation or dual-antiplatelet therapy. However, the rate of procedure- or device-related major bleeding was only 3.2%; the other 7.1% was unrelated to Amulet and reflected the underlying high risk of the study population.

The 1-year mortality rate was 8.4%. Thirty-five deaths had cardiovascular causes, 35 were noncardiovascular, and in 18 patients, cause of death couldn’t be determined.

The device-related thrombus rate through 1 year was 1.7%; 10 of 18 cases occurred within the first 90 days.

Dr. Landmesser emphasized that this was a particularly rigorously conducted registry. A unique feature was its use of an independent echocardiography core lab to assess procedural success, as well as an independent clinical events committee to adjudicate serious adverse events. Prior studies of other left atrial appendage (LAA) occlusion devices didn’t use these measures.

The Amplatzer Amulet is a second-generation occlusion device designed for easier placement and more complete sealing than its predecessor and comes in eight sizes to address anatomic variations. At implantation, adequate LAA occlusion as defined by the echocardiography core laboratory was achieved in 99.3% of patients; at that time, 89.4% of patients had no residual flow, and another 9.9% had a residual flow of less than 3 mm. At 1-3 months of follow-up, echocardiography showed 98.4% of patients had adequate occlusion.

Session cochair Alberto Cremonesi, MD, pronounced this to be “really important data.”

“I want to stress that these device implantations were transesophageal echocardiography–guided. In my mind this is absolutely essential to your excellent long-term results,” observed Dr. Cremonesi of Maria Cecilia Hospital in Cotignola, Italy.

Asked to speculate on what outcomes might have looked like had patients been treated with an oral anticoagulant rather than the Amulet occlusion device, Dr. Landmesser predicted the major bleeding rate would have been substantially higher than 10.3%. Most of the bleeding events in the study were gastrointestinal, and the novel oral anticoagulants are known to boost the risk of GI bleeding.

But that’s speculation. He noted that two ongoing randomized trials – one in Germany, the other in Scandinavia – are randomizing high-risk patients to a LAA occlusion device or best medical care, including a novel oral anticoagulant when not contraindicated. The Scandinavian study uses the Amulet, while the German trial uses both the Amulet and the Watchman device. The primary endpoint is the ischemic stroke rate.

The Amulet registry, which will continue for a second year of follow-up, was sponsored by Abbott Laboratories, which developed the Amulet device. Dr. Landmesser reported serving as a consultant to Abbott, as well as Biotronik, Rewa, and Bayer.

[email protected]

PARIS – The Amplatzer Amulet left atrial appendage occlusion device reduced stroke risk by nearly 60% at 1 year in a large, real-world registry of patients with atrial fibrillation at dual high risk for stroke and bleeding, Ulf Landmesser, MD, reported at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

One of the most impressive findings was that this feat was accomplished by and large without background oral anticoagulation. Indeed, 83% of the 1,088 patients in this 61-center, 17-country study had contraindications to oral anticoagulation. Only 11% of subjects were discharged on oral anticoagulation after device implantation, while 22.5% were discharged on aspirin or clopidogrel monotherapy. By 1-3 months post implantation, 60% of patients were either on a single antiplatelet agent or no antithrombotic medication at all.

Bruce Jancin/MDedge News

“Antithrombotic therapy was individualized by the patient’s physician. There didn’t seem to be an increased risk of device-related thrombus in these patients on single antiplatelet therapy. Our data suggest that, given the high bleeding risk, single antiplatelet therapy seems to be a good option for these patients,” said Dr. Landmesser, a professor in and the chair of the department of cardiology at Charité Medical School in Berlin.

Participants in the Global Prospective Amulet Study averaged 75 years of age, and 72% had a history of major bleeding. The average CHA2DS2-VASc score was 4.2, with a HAS-BLED score of 3.3, which emphasizes the high-risk nature of study participants.

On the basis of the CHA2DS2-VASc score, the predicted 1-year ischemic stroke rate without oral anticoagulation was 6.7%, so the actual 2.9% rate represented a 57% reduction in risk. Similarly, for the composite endpoint of ischemic stroke, transient ischemic attack, or systemic embolism, the predicted rate was 9.4%, but the achieved rate was 3.8%, which represented a 60% reduction in risk.

The annualized major bleeding rate was 10.3% despite the low usage of oral anticoagulation or dual-antiplatelet therapy. However, the rate of procedure- or device-related major bleeding was only 3.2%; the other 7.1% was unrelated to Amulet and reflected the underlying high risk of the study population.

The 1-year mortality rate was 8.4%. Thirty-five deaths had cardiovascular causes, 35 were noncardiovascular, and in 18 patients, cause of death couldn’t be determined.

The device-related thrombus rate through 1 year was 1.7%; 10 of 18 cases occurred within the first 90 days.

Dr. Landmesser emphasized that this was a particularly rigorously conducted registry. A unique feature was its use of an independent echocardiography core lab to assess procedural success, as well as an independent clinical events committee to adjudicate serious adverse events. Prior studies of other left atrial appendage (LAA) occlusion devices didn’t use these measures.

The Amplatzer Amulet is a second-generation occlusion device designed for easier placement and more complete sealing than its predecessor and comes in eight sizes to address anatomic variations. At implantation, adequate LAA occlusion as defined by the echocardiography core laboratory was achieved in 99.3% of patients; at that time, 89.4% of patients had no residual flow, and another 9.9% had a residual flow of less than 3 mm. At 1-3 months of follow-up, echocardiography showed 98.4% of patients had adequate occlusion.

Session cochair Alberto Cremonesi, MD, pronounced this to be “really important data.”

“I want to stress that these device implantations were transesophageal echocardiography–guided. In my mind this is absolutely essential to your excellent long-term results,” observed Dr. Cremonesi of Maria Cecilia Hospital in Cotignola, Italy.

Asked to speculate on what outcomes might have looked like had patients been treated with an oral anticoagulant rather than the Amulet occlusion device, Dr. Landmesser predicted the major bleeding rate would have been substantially higher than 10.3%. Most of the bleeding events in the study were gastrointestinal, and the novel oral anticoagulants are known to boost the risk of GI bleeding.

But that’s speculation. He noted that two ongoing randomized trials – one in Germany, the other in Scandinavia – are randomizing high-risk patients to a LAA occlusion device or best medical care, including a novel oral anticoagulant when not contraindicated. The Scandinavian study uses the Amulet, while the German trial uses both the Amulet and the Watchman device. The primary endpoint is the ischemic stroke rate.

The Amulet registry, which will continue for a second year of follow-up, was sponsored by Abbott Laboratories, which developed the Amulet device. Dr. Landmesser reported serving as a consultant to Abbott, as well as Biotronik, Rewa, and Bayer.

[email protected]

PARIS – The Amplatzer Amulet left atrial appendage occlusion device reduced stroke risk by nearly 60% at 1 year in a large, real-world registry of patients with atrial fibrillation at dual high risk for stroke and bleeding, Ulf Landmesser, MD, reported at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

One of the most impressive findings was that this feat was accomplished by and large without background oral anticoagulation. Indeed, 83% of the 1,088 patients in this 61-center, 17-country study had contraindications to oral anticoagulation. Only 11% of subjects were discharged on oral anticoagulation after device implantation, while 22.5% were discharged on aspirin or clopidogrel monotherapy. By 1-3 months post implantation, 60% of patients were either on a single antiplatelet agent or no antithrombotic medication at all.

Bruce Jancin/MDedge News

“Antithrombotic therapy was individualized by the patient’s physician. There didn’t seem to be an increased risk of device-related thrombus in these patients on single antiplatelet therapy. Our data suggest that, given the high bleeding risk, single antiplatelet therapy seems to be a good option for these patients,” said Dr. Landmesser, a professor in and the chair of the department of cardiology at Charité Medical School in Berlin.

Participants in the Global Prospective Amulet Study averaged 75 years of age, and 72% had a history of major bleeding. The average CHA2DS2-VASc score was 4.2, with a HAS-BLED score of 3.3, which emphasizes the high-risk nature of study participants.

On the basis of the CHA2DS2-VASc score, the predicted 1-year ischemic stroke rate without oral anticoagulation was 6.7%, so the actual 2.9% rate represented a 57% reduction in risk. Similarly, for the composite endpoint of ischemic stroke, transient ischemic attack, or systemic embolism, the predicted rate was 9.4%, but the achieved rate was 3.8%, which represented a 60% reduction in risk.

The annualized major bleeding rate was 10.3% despite the low usage of oral anticoagulation or dual-antiplatelet therapy. However, the rate of procedure- or device-related major bleeding was only 3.2%; the other 7.1% was unrelated to Amulet and reflected the underlying high risk of the study population.

The 1-year mortality rate was 8.4%. Thirty-five deaths had cardiovascular causes, 35 were noncardiovascular, and in 18 patients, cause of death couldn’t be determined.

The device-related thrombus rate through 1 year was 1.7%; 10 of 18 cases occurred within the first 90 days.

Dr. Landmesser emphasized that this was a particularly rigorously conducted registry. A unique feature was its use of an independent echocardiography core lab to assess procedural success, as well as an independent clinical events committee to adjudicate serious adverse events. Prior studies of other left atrial appendage (LAA) occlusion devices didn’t use these measures.

The Amplatzer Amulet is a second-generation occlusion device designed for easier placement and more complete sealing than its predecessor and comes in eight sizes to address anatomic variations. At implantation, adequate LAA occlusion as defined by the echocardiography core laboratory was achieved in 99.3% of patients; at that time, 89.4% of patients had no residual flow, and another 9.9% had a residual flow of less than 3 mm. At 1-3 months of follow-up, echocardiography showed 98.4% of patients had adequate occlusion.

Session cochair Alberto Cremonesi, MD, pronounced this to be “really important data.”

“I want to stress that these device implantations were transesophageal echocardiography–guided. In my mind this is absolutely essential to your excellent long-term results,” observed Dr. Cremonesi of Maria Cecilia Hospital in Cotignola, Italy.

Asked to speculate on what outcomes might have looked like had patients been treated with an oral anticoagulant rather than the Amulet occlusion device, Dr. Landmesser predicted the major bleeding rate would have been substantially higher than 10.3%. Most of the bleeding events in the study were gastrointestinal, and the novel oral anticoagulants are known to boost the risk of GI bleeding.

But that’s speculation. He noted that two ongoing randomized trials – one in Germany, the other in Scandinavia – are randomizing high-risk patients to a LAA occlusion device or best medical care, including a novel oral anticoagulant when not contraindicated. The Scandinavian study uses the Amulet, while the German trial uses both the Amulet and the Watchman device. The primary endpoint is the ischemic stroke rate.

The Amulet registry, which will continue for a second year of follow-up, was sponsored by Abbott Laboratories, which developed the Amulet device. Dr. Landmesser reported serving as a consultant to Abbott, as well as Biotronik, Rewa, and Bayer.

[email protected]

CHICAGO – The CD19–directed chimeric antigen receptor (CAR) T-cell product lisocabtagene maraleucel (liso-cel, JCAR017) produced durable responses in poor-prognosis patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), follow-up results of a phase 1 trial show.

Nearly 90% of DLBCL patients who achieved complete response as their best response on liso-cel were alive at 1 year in the study, according to investigator Jeremy S. Abramson, MD, of Massachusetts General Hospital Cancer Center in Boston.

That result is “far superior to what we would have anticipated with conventional therapies in a largely chemorefractory DLBCL population,” Dr. Abramson said at the annual meeting of the American Society of Clinical Oncology.

The new data on liso-cel come on the heels of a second approval of a CAR T-cell therapy for DLBCL, noted Caron Jacobson, MD, of Dana-Farber Cancer Institute, Boston.

Axicabtagene ciloleucel (Yescarta) was approved in October 2017 by the U.S. Food and Drug Administration for relapsed or refractory large B-cell lymphomas, including DLBCL. In May 2018, tisagenlecleucel (Kymriah) received its second FDA approval to treat relapsed or refractory large B-cell lymphomas, including DLBCL.

CAR T-cell therapy “really has transformed outcomes for a group of patients who previously had no other standard of care and who… have a relatively short overall survival,” Dr. Jacobson said.

At the meeting, Dr. Abramson presented findings on DLBCL patients in TRANSCEND NHL 001, a phase 1, multicenter, open-label study of the CD-19 targeted CAR T-cell therapy in relapsed and refractory B-cell non-Hodgkin lymphoma.

About 90% of treated DLBCL patients had one or more poor-risk disease features, such as ECOG performance status 2 and primary refractory disease, which predict poor overall survival, according to Dr. Abramson.

Dr. Abramson’s presentation focused on 102 evaluable DLBCL patients in the dose-finding and dose-expansion cohorts of the TRANSCEND study, including a subset analysis of a core group of 73 patients who met the criteria for pivotal dose cohort of the study (1 x 10⁸ cells given as a single dose).

For the full set of 102 DLBCL patients, the best overall response rate was 75%, including a best complete remission rate of 55%, according to presented data. In the core group of 73 DLBCL patients, best overall response and complete remission rates were 80% and 59%, respectively.

Investigators saw “encouraging” durable response rates at 6 months and beyond in the core DLBCL population, according to Dr. Abramson. Of patients with a complete remission at 3 months, 88% remained in complete remission at the 6-month follow-up, and 93% of those in remission at the 6-month time point were in ongoing response at a median follow-up of 8 months.

Median overall survival had not been reached in either the full or core DLBCL cohorts with a median of 12 months follow-up, he added, noting that 90% of patients who achieved complete remission as their best response remained alive at 1 year.

In terms of adverse effects, liso-cel is showing a low and manageable toxicity profile, with very low rates of severe cytokine release syndrome (CRS) and neurotoxicity at 1% and 13%, respectively, Dr. Abramson reported.

“This anti-CD19 CAR T cell has remarkable efficacy in a group of highly refractory aggressive B-cell non-Hodgkin lymphoma patients,” said Dr. Jacobson, commenting on results of the DLBCL subset.

Based on the data presented, liso-cel is “clearly competitive” with the approved CAR T-cell therapies, though she advised caution in comparing across studies. “I don’t think that there will be a randomized study of all three agents, but I do think that we’ll start to get comparative data from single institution experiences that are using all three products,” she said.

The pivotal DLBCL cohort of TRANSCEND NHL 001 has completed accrual and results will be presented at a future meeting, Dr. Abramson said.

Dr. Abramson reported disclosures related to Celgene, Genentech/Roche, Gilead Sciences, Novartis, Seattle Genetics, and Millennium.

SOURCE: Abramson JS et al. ASCO 2018. Abstract 7505.

CHICAGO – The CD19–directed chimeric antigen receptor (CAR) T-cell product lisocabtagene maraleucel (liso-cel, JCAR017) produced durable responses in poor-prognosis patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), follow-up results of a phase 1 trial show.

Nearly 90% of DLBCL patients who achieved complete response as their best response on liso-cel were alive at 1 year in the study, according to investigator Jeremy S. Abramson, MD, of Massachusetts General Hospital Cancer Center in Boston.

That result is “far superior to what we would have anticipated with conventional therapies in a largely chemorefractory DLBCL population,” Dr. Abramson said at the annual meeting of the American Society of Clinical Oncology.

The new data on liso-cel come on the heels of a second approval of a CAR T-cell therapy for DLBCL, noted Caron Jacobson, MD, of Dana-Farber Cancer Institute, Boston.

Axicabtagene ciloleucel (Yescarta) was approved in October 2017 by the U.S. Food and Drug Administration for relapsed or refractory large B-cell lymphomas, including DLBCL. In May 2018, tisagenlecleucel (Kymriah) received its second FDA approval to treat relapsed or refractory large B-cell lymphomas, including DLBCL.

CAR T-cell therapy “really has transformed outcomes for a group of patients who previously had no other standard of care and who… have a relatively short overall survival,” Dr. Jacobson said.

At the meeting, Dr. Abramson presented findings on DLBCL patients in TRANSCEND NHL 001, a phase 1, multicenter, open-label study of the CD-19 targeted CAR T-cell therapy in relapsed and refractory B-cell non-Hodgkin lymphoma.

About 90% of treated DLBCL patients had one or more poor-risk disease features, such as ECOG performance status 2 and primary refractory disease, which predict poor overall survival, according to Dr. Abramson.

Dr. Abramson’s presentation focused on 102 evaluable DLBCL patients in the dose-finding and dose-expansion cohorts of the TRANSCEND study, including a subset analysis of a core group of 73 patients who met the criteria for pivotal dose cohort of the study (1 x 10⁸ cells given as a single dose).

For the full set of 102 DLBCL patients, the best overall response rate was 75%, including a best complete remission rate of 55%, according to presented data. In the core group of 73 DLBCL patients, best overall response and complete remission rates were 80% and 59%, respectively.

Investigators saw “encouraging” durable response rates at 6 months and beyond in the core DLBCL population, according to Dr. Abramson. Of patients with a complete remission at 3 months, 88% remained in complete remission at the 6-month follow-up, and 93% of those in remission at the 6-month time point were in ongoing response at a median follow-up of 8 months.

Median overall survival had not been reached in either the full or core DLBCL cohorts with a median of 12 months follow-up, he added, noting that 90% of patients who achieved complete remission as their best response remained alive at 1 year.

In terms of adverse effects, liso-cel is showing a low and manageable toxicity profile, with very low rates of severe cytokine release syndrome (CRS) and neurotoxicity at 1% and 13%, respectively, Dr. Abramson reported.

“This anti-CD19 CAR T cell has remarkable efficacy in a group of highly refractory aggressive B-cell non-Hodgkin lymphoma patients,” said Dr. Jacobson, commenting on results of the DLBCL subset.

Based on the data presented, liso-cel is “clearly competitive” with the approved CAR T-cell therapies, though she advised caution in comparing across studies. “I don’t think that there will be a randomized study of all three agents, but I do think that we’ll start to get comparative data from single institution experiences that are using all three products,” she said.

The pivotal DLBCL cohort of TRANSCEND NHL 001 has completed accrual and results will be presented at a future meeting, Dr. Abramson said.

Dr. Abramson reported disclosures related to Celgene, Genentech/Roche, Gilead Sciences, Novartis, Seattle Genetics, and Millennium.

SOURCE: Abramson JS et al. ASCO 2018. Abstract 7505.

CHICAGO – The CD19–directed chimeric antigen receptor (CAR) T-cell product lisocabtagene maraleucel (liso-cel, JCAR017) produced durable responses in poor-prognosis patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), follow-up results of a phase 1 trial show.

Nearly 90% of DLBCL patients who achieved complete response as their best response on liso-cel were alive at 1 year in the study, according to investigator Jeremy S. Abramson, MD, of Massachusetts General Hospital Cancer Center in Boston.

That result is “far superior to what we would have anticipated with conventional therapies in a largely chemorefractory DLBCL population,” Dr. Abramson said at the annual meeting of the American Society of Clinical Oncology.

The new data on liso-cel come on the heels of a second approval of a CAR T-cell therapy for DLBCL, noted Caron Jacobson, MD, of Dana-Farber Cancer Institute, Boston.

Axicabtagene ciloleucel (Yescarta) was approved in October 2017 by the U.S. Food and Drug Administration for relapsed or refractory large B-cell lymphomas, including DLBCL. In May 2018, tisagenlecleucel (Kymriah) received its second FDA approval to treat relapsed or refractory large B-cell lymphomas, including DLBCL.

CAR T-cell therapy “really has transformed outcomes for a group of patients who previously had no other standard of care and who… have a relatively short overall survival,” Dr. Jacobson said.

At the meeting, Dr. Abramson presented findings on DLBCL patients in TRANSCEND NHL 001, a phase 1, multicenter, open-label study of the CD-19 targeted CAR T-cell therapy in relapsed and refractory B-cell non-Hodgkin lymphoma.

About 90% of treated DLBCL patients had one or more poor-risk disease features, such as ECOG performance status 2 and primary refractory disease, which predict poor overall survival, according to Dr. Abramson.

Dr. Abramson’s presentation focused on 102 evaluable DLBCL patients in the dose-finding and dose-expansion cohorts of the TRANSCEND study, including a subset analysis of a core group of 73 patients who met the criteria for pivotal dose cohort of the study (1 x 10⁸ cells given as a single dose).

For the full set of 102 DLBCL patients, the best overall response rate was 75%, including a best complete remission rate of 55%, according to presented data. In the core group of 73 DLBCL patients, best overall response and complete remission rates were 80% and 59%, respectively.

Investigators saw “encouraging” durable response rates at 6 months and beyond in the core DLBCL population, according to Dr. Abramson. Of patients with a complete remission at 3 months, 88% remained in complete remission at the 6-month follow-up, and 93% of those in remission at the 6-month time point were in ongoing response at a median follow-up of 8 months.

Median overall survival had not been reached in either the full or core DLBCL cohorts with a median of 12 months follow-up, he added, noting that 90% of patients who achieved complete remission as their best response remained alive at 1 year.

In terms of adverse effects, liso-cel is showing a low and manageable toxicity profile, with very low rates of severe cytokine release syndrome (CRS) and neurotoxicity at 1% and 13%, respectively, Dr. Abramson reported.

“This anti-CD19 CAR T cell has remarkable efficacy in a group of highly refractory aggressive B-cell non-Hodgkin lymphoma patients,” said Dr. Jacobson, commenting on results of the DLBCL subset.

Based on the data presented, liso-cel is “clearly competitive” with the approved CAR T-cell therapies, though she advised caution in comparing across studies. “I don’t think that there will be a randomized study of all three agents, but I do think that we’ll start to get comparative data from single institution experiences that are using all three products,” she said.

The pivotal DLBCL cohort of TRANSCEND NHL 001 has completed accrual and results will be presented at a future meeting, Dr. Abramson said.

Dr. Abramson reported disclosures related to Celgene, Genentech/Roche, Gilead Sciences, Novartis, Seattle Genetics, and Millennium.

SOURCE: Abramson JS et al. ASCO 2018. Abstract 7505.

When R. Clement Darling III, MD, took to the podium at the Vascular Annual Meeting to present his presidential address, he highlighted the importance of teamwork and collaboration in training, in maintaining personal well-being, and most importantly, in patient care.

Nationwide Photographers

His talk, titled, “Looking Forward Through the Past: Changing Me to We in the Evolution of Team-based Vascular Care,” addressed these issues through a very personal lens. To make his point, Dr. Darling outlined four key take-home concepts that he had found useful “over five decades of working in an operating room as a technologist, a student and a surgeon,” and as chief of the division of vascular surgery at Albany Medical Center Hospital (N.Y.). These formed the basis of his entire address:

1. “None of us is as smart as all of us.” We learn from each other which is the foundation of team-based training.

2. The key to resilience, healing and health, whether for our patients or for ourselves, is caring and supporting each other more.

3. Failure is not an end result. It is the path to success through learning.

4. Remember the past but look to the future. The best predictor of future behavior is the past, but the future we are experiencing now, is like no other!”

Dr. Darling spoke from the heart about the importance of his colleagues and his parents, especially the role of his father as a pioneer in vascular surgery, and of the women in his life as role models.

He stressed how “one of the invaluable things I have learned is the value of failure, evaluating the past to avoid the same mistakes and the benefit of the TEAM in providing support and care.”

“Every day we’re asked to do the impossible and every day we get up, go to work. We do the best we can. We can make the best plans, treat the sickest patients and get a tremendous fulfillment for what we do in what we do. We do the right thing for the patient,” Dr. Darling explained, in summarizing the passion that he feels for vascular surgery.

“We are always willing to do and try the impossible. We’re always willing to be the last person to call when things look bleak. It brings me great glee whenever we get called to the operating room and people look around and go, ‘oh thank God, the vascular surgeon’s here.’ Our colleagues in other specialties are often afraid of blood vessels, afraid of death, afraid of complications. We thrust ourselves every day into situations where nobody else will go,” he added.

“As vascular surgeons we face failure and roadblocks daily yet still persist where others are scared to tread. Many of you have faced far worse barriers of discrimination and unreasonable arbitrary barriers, and I am constantly humbled by your ability to overcome them,” Dr. Darling said. He pointed out that: “This innate ability to focus on the problem is what makes vascular surgeons great. No problem is too complex, no detail is too small. We do the right thing despite the odds against us. We do right by the patient.”

After telling some of his own stories of “failure,” to illustrate its importance as a learning tool, Dr. Darling spoke of one person’s reception of his application to join the SVS: “When I applied for membership to the Society for Vascular Surgery, someone had written a note saying that ‘I should never be considered, nor was I deserving to be a member of the SVS, and never should I be admitted into this austere society.’”

Throughout his address, Dr. Darling re-emphasized the importance of teams and the collaborative nature of patient care. “The SVS has developed strong partnerships with the Society for Vascular Nursing, The American Venous Forum, The Society for Vascular Ultrasound, and is seeking to strengthen relationships with the regional vascular societies, VESS, the Society for Clinical Vascular Surgery, The Society for Vascular Medicine, the American Heart Association, and many others.

“The SVS is developing these relationships with the patient at the center, and with purpose, focusing on ‘shared vision,’ of specific advancements, programs, and initiatives that will advance quality of care. By tapping into this vast array of talent Vascular Surgery will become more agile, intelligent and thoughtful in our care of vascular patients,” Dr. Darling predicted.

But vascular surgeons must become comfortable with moving from the concept of “captain of the ship” to the role of team leadership, he emphasized, if they are to truly succeed in their careers and in providing optimal patient care.

“Currently, each patient coming to your service touches over 100 staff during their experience. This includes your office, vascular lab, angio suite, recovery room, hospital floor, ICU, CT scanner to name a few.” This is part of the need for the evolution from ‘captain’ to ‘leader,’ he added.

“If you have not had any formal training in leadership or team development, I strongly suggest you add this to your learning portfolio,” Dr. Darling counseled. “The SVS is addressing this through its Leadership and Diversity Committee, and you will see an expanding array of learning opportunities in the future.”

With regard to his own tenure as SVS President: “I am proud that during my year as president, the SVS has invested in several new Task Forces to address critical future issues including: Alternative Payment Models for vascular surgery; a national inpatient and outpatient vascular certification program; a focus on our own health, wellness, and potential ways to mitigate potential burnout; and Dr. Makaroun will be taking on the issues of vascular surgery valuation and workforce in the new Task Force on the Future of Vascular Surgery.”

He further discussed the role SVS is playing in helping to define the future of vascular surgery.

“As we work to strengthen our brand and identity, the SVS Executive Board has supported, and thanks, Amy Reed and Will Jordan for their leadership in the APDVS [Association of Program Directors of Vascular Surgery], and for taking the first step toward attaining a separate Vascular Residency Review Committee or RRC.” In addition, he described how “SVS is also working closely, and collaboratively, with the American Board of Surgery, and the Vascular Surgery Board, to complete the work that was begun a decade ago, and achieve an autonomous vascular surgery board that is an equal partner and stakeholder in the ABS.”

Dr. Darling then outlined one of his major concerns and interests: the exit path of senior vascular surgeons, and how this is often a tremendous waste of talent and expertise. “In the last decade of work when senior surgeons are trying to transition to non-clinical work, I think we throw away much of their intellectual skill and experience in dealing with vascular surgery problems,” he said. He urged that “as our senior surgeons leave clinical practice, we need to use their intellectual expertise and experience in a more productive way.”

The Society for Vascular Surgery is establishing pathways for leadership and pathways to train people in administration, he added.

Turning back to the extreme importance of teamwork, Dr. Darling addressed the future.

“We, physicians, nurses, PAs, technologists, staff, and administrators, need to work together, think together, to grow together, not only for our patients, but for our partners and our families. We are all part of the vascular team,” Dr. Darling said. 

When R. Clement Darling III, MD, took to the podium at the Vascular Annual Meeting to present his presidential address, he highlighted the importance of teamwork and collaboration in training, in maintaining personal well-being, and most importantly, in patient care.

Nationwide Photographers

His talk, titled, “Looking Forward Through the Past: Changing Me to We in the Evolution of Team-based Vascular Care,” addressed these issues through a very personal lens. To make his point, Dr. Darling outlined four key take-home concepts that he had found useful “over five decades of working in an operating room as a technologist, a student and a surgeon,” and as chief of the division of vascular surgery at Albany Medical Center Hospital (N.Y.). These formed the basis of his entire address:

1. “None of us is as smart as all of us.” We learn from each other which is the foundation of team-based training.

2. The key to resilience, healing and health, whether for our patients or for ourselves, is caring and supporting each other more.

3. Failure is not an end result. It is the path to success through learning.

4. Remember the past but look to the future. The best predictor of future behavior is the past, but the future we are experiencing now, is like no other!”

Dr. Darling spoke from the heart about the importance of his colleagues and his parents, especially the role of his father as a pioneer in vascular surgery, and of the women in his life as role models.

He stressed how “one of the invaluable things I have learned is the value of failure, evaluating the past to avoid the same mistakes and the benefit of the TEAM in providing support and care.”

“Every day we’re asked to do the impossible and every day we get up, go to work. We do the best we can. We can make the best plans, treat the sickest patients and get a tremendous fulfillment for what we do in what we do. We do the right thing for the patient,” Dr. Darling explained, in summarizing the passion that he feels for vascular surgery.

“We are always willing to do and try the impossible. We’re always willing to be the last person to call when things look bleak. It brings me great glee whenever we get called to the operating room and people look around and go, ‘oh thank God, the vascular surgeon’s here.’ Our colleagues in other specialties are often afraid of blood vessels, afraid of death, afraid of complications. We thrust ourselves every day into situations where nobody else will go,” he added.

“As vascular surgeons we face failure and roadblocks daily yet still persist where others are scared to tread. Many of you have faced far worse barriers of discrimination and unreasonable arbitrary barriers, and I am constantly humbled by your ability to overcome them,” Dr. Darling said. He pointed out that: “This innate ability to focus on the problem is what makes vascular surgeons great. No problem is too complex, no detail is too small. We do the right thing despite the odds against us. We do right by the patient.”

After telling some of his own stories of “failure,” to illustrate its importance as a learning tool, Dr. Darling spoke of one person’s reception of his application to join the SVS: “When I applied for membership to the Society for Vascular Surgery, someone had written a note saying that ‘I should never be considered, nor was I deserving to be a member of the SVS, and never should I be admitted into this austere society.’”

Throughout his address, Dr. Darling re-emphasized the importance of teams and the collaborative nature of patient care. “The SVS has developed strong partnerships with the Society for Vascular Nursing, The American Venous Forum, The Society for Vascular Ultrasound, and is seeking to strengthen relationships with the regional vascular societies, VESS, the Society for Clinical Vascular Surgery, The Society for Vascular Medicine, the American Heart Association, and many others.

“The SVS is developing these relationships with the patient at the center, and with purpose, focusing on ‘shared vision,’ of specific advancements, programs, and initiatives that will advance quality of care. By tapping into this vast array of talent Vascular Surgery will become more agile, intelligent and thoughtful in our care of vascular patients,” Dr. Darling predicted.

But vascular surgeons must become comfortable with moving from the concept of “captain of the ship” to the role of team leadership, he emphasized, if they are to truly succeed in their careers and in providing optimal patient care.

“Currently, each patient coming to your service touches over 100 staff during their experience. This includes your office, vascular lab, angio suite, recovery room, hospital floor, ICU, CT scanner to name a few.” This is part of the need for the evolution from ‘captain’ to ‘leader,’ he added.

“If you have not had any formal training in leadership or team development, I strongly suggest you add this to your learning portfolio,” Dr. Darling counseled. “The SVS is addressing this through its Leadership and Diversity Committee, and you will see an expanding array of learning opportunities in the future.”

With regard to his own tenure as SVS President: “I am proud that during my year as president, the SVS has invested in several new Task Forces to address critical future issues including: Alternative Payment Models for vascular surgery; a national inpatient and outpatient vascular certification program; a focus on our own health, wellness, and potential ways to mitigate potential burnout; and Dr. Makaroun will be taking on the issues of vascular surgery valuation and workforce in the new Task Force on the Future of Vascular Surgery.”

He further discussed the role SVS is playing in helping to define the future of vascular surgery.

“As we work to strengthen our brand and identity, the SVS Executive Board has supported, and thanks, Amy Reed and Will Jordan for their leadership in the APDVS [Association of Program Directors of Vascular Surgery], and for taking the first step toward attaining a separate Vascular Residency Review Committee or RRC.” In addition, he described how “SVS is also working closely, and collaboratively, with the American Board of Surgery, and the Vascular Surgery Board, to complete the work that was begun a decade ago, and achieve an autonomous vascular surgery board that is an equal partner and stakeholder in the ABS.”

Dr. Darling then outlined one of his major concerns and interests: the exit path of senior vascular surgeons, and how this is often a tremendous waste of talent and expertise. “In the last decade of work when senior surgeons are trying to transition to non-clinical work, I think we throw away much of their intellectual skill and experience in dealing with vascular surgery problems,” he said. He urged that “as our senior surgeons leave clinical practice, we need to use their intellectual expertise and experience in a more productive way.”

The Society for Vascular Surgery is establishing pathways for leadership and pathways to train people in administration, he added.

Turning back to the extreme importance of teamwork, Dr. Darling addressed the future.

“We, physicians, nurses, PAs, technologists, staff, and administrators, need to work together, think together, to grow together, not only for our patients, but for our partners and our families. We are all part of the vascular team,” Dr. Darling said. 

When R. Clement Darling III, MD, took to the podium at the Vascular Annual Meeting to present his presidential address, he highlighted the importance of teamwork and collaboration in training, in maintaining personal well-being, and most importantly, in patient care.

Nationwide Photographers

His talk, titled, “Looking Forward Through the Past: Changing Me to We in the Evolution of Team-based Vascular Care,” addressed these issues through a very personal lens. To make his point, Dr. Darling outlined four key take-home concepts that he had found useful “over five decades of working in an operating room as a technologist, a student and a surgeon,” and as chief of the division of vascular surgery at Albany Medical Center Hospital (N.Y.). These formed the basis of his entire address:

1. “None of us is as smart as all of us.” We learn from each other which is the foundation of team-based training.

2. The key to resilience, healing and health, whether for our patients or for ourselves, is caring and supporting each other more.

3. Failure is not an end result. It is the path to success through learning.

4. Remember the past but look to the future. The best predictor of future behavior is the past, but the future we are experiencing now, is like no other!”

Dr. Darling spoke from the heart about the importance of his colleagues and his parents, especially the role of his father as a pioneer in vascular surgery, and of the women in his life as role models.

He stressed how “one of the invaluable things I have learned is the value of failure, evaluating the past to avoid the same mistakes and the benefit of the TEAM in providing support and care.”

“Every day we’re asked to do the impossible and every day we get up, go to work. We do the best we can. We can make the best plans, treat the sickest patients and get a tremendous fulfillment for what we do in what we do. We do the right thing for the patient,” Dr. Darling explained, in summarizing the passion that he feels for vascular surgery.

“We are always willing to do and try the impossible. We’re always willing to be the last person to call when things look bleak. It brings me great glee whenever we get called to the operating room and people look around and go, ‘oh thank God, the vascular surgeon’s here.’ Our colleagues in other specialties are often afraid of blood vessels, afraid of death, afraid of complications. We thrust ourselves every day into situations where nobody else will go,” he added.

“As vascular surgeons we face failure and roadblocks daily yet still persist where others are scared to tread. Many of you have faced far worse barriers of discrimination and unreasonable arbitrary barriers, and I am constantly humbled by your ability to overcome them,” Dr. Darling said. He pointed out that: “This innate ability to focus on the problem is what makes vascular surgeons great. No problem is too complex, no detail is too small. We do the right thing despite the odds against us. We do right by the patient.”

After telling some of his own stories of “failure,” to illustrate its importance as a learning tool, Dr. Darling spoke of one person’s reception of his application to join the SVS: “When I applied for membership to the Society for Vascular Surgery, someone had written a note saying that ‘I should never be considered, nor was I deserving to be a member of the SVS, and never should I be admitted into this austere society.’”

Throughout his address, Dr. Darling re-emphasized the importance of teams and the collaborative nature of patient care. “The SVS has developed strong partnerships with the Society for Vascular Nursing, The American Venous Forum, The Society for Vascular Ultrasound, and is seeking to strengthen relationships with the regional vascular societies, VESS, the Society for Clinical Vascular Surgery, The Society for Vascular Medicine, the American Heart Association, and many others.

“The SVS is developing these relationships with the patient at the center, and with purpose, focusing on ‘shared vision,’ of specific advancements, programs, and initiatives that will advance quality of care. By tapping into this vast array of talent Vascular Surgery will become more agile, intelligent and thoughtful in our care of vascular patients,” Dr. Darling predicted.

But vascular surgeons must become comfortable with moving from the concept of “captain of the ship” to the role of team leadership, he emphasized, if they are to truly succeed in their careers and in providing optimal patient care.

“Currently, each patient coming to your service touches over 100 staff during their experience. This includes your office, vascular lab, angio suite, recovery room, hospital floor, ICU, CT scanner to name a few.” This is part of the need for the evolution from ‘captain’ to ‘leader,’ he added.

“If you have not had any formal training in leadership or team development, I strongly suggest you add this to your learning portfolio,” Dr. Darling counseled. “The SVS is addressing this through its Leadership and Diversity Committee, and you will see an expanding array of learning opportunities in the future.”

With regard to his own tenure as SVS President: “I am proud that during my year as president, the SVS has invested in several new Task Forces to address critical future issues including: Alternative Payment Models for vascular surgery; a national inpatient and outpatient vascular certification program; a focus on our own health, wellness, and potential ways to mitigate potential burnout; and Dr. Makaroun will be taking on the issues of vascular surgery valuation and workforce in the new Task Force on the Future of Vascular Surgery.”

He further discussed the role SVS is playing in helping to define the future of vascular surgery.

“As we work to strengthen our brand and identity, the SVS Executive Board has supported, and thanks, Amy Reed and Will Jordan for their leadership in the APDVS [Association of Program Directors of Vascular Surgery], and for taking the first step toward attaining a separate Vascular Residency Review Committee or RRC.” In addition, he described how “SVS is also working closely, and collaboratively, with the American Board of Surgery, and the Vascular Surgery Board, to complete the work that was begun a decade ago, and achieve an autonomous vascular surgery board that is an equal partner and stakeholder in the ABS.”

Dr. Darling then outlined one of his major concerns and interests: the exit path of senior vascular surgeons, and how this is often a tremendous waste of talent and expertise. “In the last decade of work when senior surgeons are trying to transition to non-clinical work, I think we throw away much of their intellectual skill and experience in dealing with vascular surgery problems,” he said. He urged that “as our senior surgeons leave clinical practice, we need to use their intellectual expertise and experience in a more productive way.”

The Society for Vascular Surgery is establishing pathways for leadership and pathways to train people in administration, he added.

Turning back to the extreme importance of teamwork, Dr. Darling addressed the future.

“We, physicians, nurses, PAs, technologists, staff, and administrators, need to work together, think together, to grow together, not only for our patients, but for our partners and our families. We are all part of the vascular team,” Dr. Darling said. 

The parvovirus known as cutavirus appears unlikely to play a pathogenic role in primary cutaneous B- and T-cell lymphoma, based on data from 189 biopsies.

Although researchers have long suspected viruses of a role in primary cutaneous lymphomas, “all of the so-far-suspected viruses including retroviruses, herpesviruses, and polyomaviruses have failed to reveal a consistent association with both cutaneous B-cell lymphoma [CBCL] and cutaneous T-cell lymphoma [CTCL],” wrote Alexander Kreuter, MD, of the department of dermatology, venereology, and allergology at Helios St. Elisabeth Hospital Oberhausen, Germany, and his colleagues.

In a research letter published in JAMA Dermatology, the researchers analyzed 189 paraffin-embedded biopsy specimens from 130 adults with CBCL or CTCL.

Overall, cutavirus DNA was identified in 6 (3.2%) of the 189 lymphoma biopsies and in 6 (4.6%) of 130 patients. Cutavirus was identified only in male patients with mycosis fungoides, and no cutavirus was identified in patients or biopsies without mycosis fungoides, the researchers noted. Viral DNA loads in the cutavirus-positive biopsies ranged from 1.3 to 85.0 cutavirus DNA copies per beta globin gene copy.

The findings were limited by several factors, such as the lack of biopsy samples for some lymphoma subtypes and the availability of a single specimen from most patients, the researchers noted. However, the analysis of a large number of samples suggested that cutavirus is not associated with the development of most primary cutaneous lymphomas, they said.

The study was funded by the German National Reference Center for Papilloma- and Polyomaviruses. The researchers had no financial conflicts to disclose.

SOURCE: Kreuter A et al. JAMA Dermatol. 2018 Jun 27. doi:10.1001/jamadermatol.2018.1628.

The parvovirus known as cutavirus appears unlikely to play a pathogenic role in primary cutaneous B- and T-cell lymphoma, based on data from 189 biopsies.

Although researchers have long suspected viruses of a role in primary cutaneous lymphomas, “all of the so-far-suspected viruses including retroviruses, herpesviruses, and polyomaviruses have failed to reveal a consistent association with both cutaneous B-cell lymphoma [CBCL] and cutaneous T-cell lymphoma [CTCL],” wrote Alexander Kreuter, MD, of the department of dermatology, venereology, and allergology at Helios St. Elisabeth Hospital Oberhausen, Germany, and his colleagues.

In a research letter published in JAMA Dermatology, the researchers analyzed 189 paraffin-embedded biopsy specimens from 130 adults with CBCL or CTCL.

Overall, cutavirus DNA was identified in 6 (3.2%) of the 189 lymphoma biopsies and in 6 (4.6%) of 130 patients. Cutavirus was identified only in male patients with mycosis fungoides, and no cutavirus was identified in patients or biopsies without mycosis fungoides, the researchers noted. Viral DNA loads in the cutavirus-positive biopsies ranged from 1.3 to 85.0 cutavirus DNA copies per beta globin gene copy.

The findings were limited by several factors, such as the lack of biopsy samples for some lymphoma subtypes and the availability of a single specimen from most patients, the researchers noted. However, the analysis of a large number of samples suggested that cutavirus is not associated with the development of most primary cutaneous lymphomas, they said.

The study was funded by the German National Reference Center for Papilloma- and Polyomaviruses. The researchers had no financial conflicts to disclose.

SOURCE: Kreuter A et al. JAMA Dermatol. 2018 Jun 27. doi:10.1001/jamadermatol.2018.1628.

The parvovirus known as cutavirus appears unlikely to play a pathogenic role in primary cutaneous B- and T-cell lymphoma, based on data from 189 biopsies.

Although researchers have long suspected viruses of a role in primary cutaneous lymphomas, “all of the so-far-suspected viruses including retroviruses, herpesviruses, and polyomaviruses have failed to reveal a consistent association with both cutaneous B-cell lymphoma [CBCL] and cutaneous T-cell lymphoma [CTCL],” wrote Alexander Kreuter, MD, of the department of dermatology, venereology, and allergology at Helios St. Elisabeth Hospital Oberhausen, Germany, and his colleagues.

In a research letter published in JAMA Dermatology, the researchers analyzed 189 paraffin-embedded biopsy specimens from 130 adults with CBCL or CTCL.

Overall, cutavirus DNA was identified in 6 (3.2%) of the 189 lymphoma biopsies and in 6 (4.6%) of 130 patients. Cutavirus was identified only in male patients with mycosis fungoides, and no cutavirus was identified in patients or biopsies without mycosis fungoides, the researchers noted. Viral DNA loads in the cutavirus-positive biopsies ranged from 1.3 to 85.0 cutavirus DNA copies per beta globin gene copy.

The findings were limited by several factors, such as the lack of biopsy samples for some lymphoma subtypes and the availability of a single specimen from most patients, the researchers noted. However, the analysis of a large number of samples suggested that cutavirus is not associated with the development of most primary cutaneous lymphomas, they said.

The study was funded by the German National Reference Center for Papilloma- and Polyomaviruses. The researchers had no financial conflicts to disclose.

SOURCE: Kreuter A et al. JAMA Dermatol. 2018 Jun 27. doi:10.1001/jamadermatol.2018.1628.

AMSTERDAM – Starting patients with newly diagnosed, peripheral spondyloarthritis (SpA) on treatment with a tumor necrosis factor (TNF) inhibitor within 12 weeks of symptom onset produced an “amazing,” long-term, complete remission that resembled cure in more than half of the 40 treated patients, a finding that now needs replication in a larger, multicenter study, Philippe Carron, MD, said at the European Congress of Rheumatology.

Ongoing research on patients in the original study cohort also showed that methotrexate is largely ineffective to help wean patients in remission on a tumor necrosis factor inhibitor off the biologic drug, said Dr. Carron, a rheumatologist at the University of Ghent (Belgium). In his group’s most recent experience with 22 patients in remission on a regimen of golimumab and methotrexate, 5 remained in remission (23%) when golimumab treatment stopped, whereas the other 17 patients had to restart golimumab (Simponi) while continuing on methotrexate after relapsing on methotrexate monotherapy, Dr. Carron reported.

Mitchel L. Zoler/MDedge News

Methotrexate has “overall weak efficacy for maintaining biological-free remission” in patients with peripheral SpA, he concluded.

But Dr. Carron remained very positive about the main finding of the CRESPA (Clinical Remission in Patients with Early Peripheral Spondyloarthritis) study, which has now shown a durable complete remission – free from arthritis, enthesitis, and dactylitis – in 21 of 40 (53%) patients who began golimumab treatment within 12 weeks of their symptom onset and then remained in remission when the golimumab was eventually stopped. These patients have now remained in complete remission for 2.4-5.8 years of follow-up, Dr. Carron said. He attributed this very durable remission while off any treatment to the rapid start of TNF-inhibitor therapy within weeks of their symptom onset.

“This is fantastic; these patients are cured. Early treatment is the most important reason why the result is so good,” but it also poses the biggest challenge for using this approach in routine practice, Dr. Carron said in an interview. “It took us 3 years to find the 60 patients” enrolled in CRESPA. “Most of the time, patients go elsewhere for treatment, and it’s several months until they see us. In many countries there are not enough rheumatologists, and patients wait 3, 4 months before we see them.” Another important feature of the intervention was that golimumab treatment continued until patients presented as completely symptom free on two consecutive clinic visits spaced about 12 weeks apart.

Dr. Carron and his associates published their initial findings from CRESPA in 2017 (Ann Rheum Dis. 2017 Aug;76[8]:1389-95), and they also have reported updates on the main results at meetings. At the 2018 EULAR Congress, Dr. Carron reported the outcomes of 31 patients in the study who entered a 2-year period of extended golimumab treatment either because they never reached complete remission or because they relapsed after stopping golimumab and so restarted the drug. Of these patients, 25 completed the full 2 years of the CRESPA extension phase on golimumab. Of those patients, 22 were in complete remission and agreed to continue; they began a tapering phase that started with receiving concurrent treatment with 15 mg/week of oral methotrexate then, after 12 weeks on methotrexate, discontinued their golimumab but continued on the methotrexate regimen.

After an average follow-up of 80 weeks in this postextension phase, 5 patients (23%) remained in remission on methotrexate monotherapy, while the other 17 patients (77%) had to restart golimumab. Of these 17 patients, 15 because of a relapse, and 2 restarted because they had to discontinue methotrexate after developing adverse effects. The median time to restarting golimumab among these 17 patients was 228 days, Dr. Carron said. In all 17 patients, remission returned within 12 weeks of restarting golimumab treatment.

[email protected]

SOURCE: Carron P et al. EULAR 2018 Congress, Abstract OP0335.

AMSTERDAM – Starting patients with newly diagnosed, peripheral spondyloarthritis (SpA) on treatment with a tumor necrosis factor (TNF) inhibitor within 12 weeks of symptom onset produced an “amazing,” long-term, complete remission that resembled cure in more than half of the 40 treated patients, a finding that now needs replication in a larger, multicenter study, Philippe Carron, MD, said at the European Congress of Rheumatology.

Ongoing research on patients in the original study cohort also showed that methotrexate is largely ineffective to help wean patients in remission on a tumor necrosis factor inhibitor off the biologic drug, said Dr. Carron, a rheumatologist at the University of Ghent (Belgium). In his group’s most recent experience with 22 patients in remission on a regimen of golimumab and methotrexate, 5 remained in remission (23%) when golimumab treatment stopped, whereas the other 17 patients had to restart golimumab (Simponi) while continuing on methotrexate after relapsing on methotrexate monotherapy, Dr. Carron reported.

Mitchel L. Zoler/MDedge News

Methotrexate has “overall weak efficacy for maintaining biological-free remission” in patients with peripheral SpA, he concluded.

But Dr. Carron remained very positive about the main finding of the CRESPA (Clinical Remission in Patients with Early Peripheral Spondyloarthritis) study, which has now shown a durable complete remission – free from arthritis, enthesitis, and dactylitis – in 21 of 40 (53%) patients who began golimumab treatment within 12 weeks of their symptom onset and then remained in remission when the golimumab was eventually stopped. These patients have now remained in complete remission for 2.4-5.8 years of follow-up, Dr. Carron said. He attributed this very durable remission while off any treatment to the rapid start of TNF-inhibitor therapy within weeks of their symptom onset.

“This is fantastic; these patients are cured. Early treatment is the most important reason why the result is so good,” but it also poses the biggest challenge for using this approach in routine practice, Dr. Carron said in an interview. “It took us 3 years to find the 60 patients” enrolled in CRESPA. “Most of the time, patients go elsewhere for treatment, and it’s several months until they see us. In many countries there are not enough rheumatologists, and patients wait 3, 4 months before we see them.” Another important feature of the intervention was that golimumab treatment continued until patients presented as completely symptom free on two consecutive clinic visits spaced about 12 weeks apart.

Dr. Carron and his associates published their initial findings from CRESPA in 2017 (Ann Rheum Dis. 2017 Aug;76[8]:1389-95), and they also have reported updates on the main results at meetings. At the 2018 EULAR Congress, Dr. Carron reported the outcomes of 31 patients in the study who entered a 2-year period of extended golimumab treatment either because they never reached complete remission or because they relapsed after stopping golimumab and so restarted the drug. Of these patients, 25 completed the full 2 years of the CRESPA extension phase on golimumab. Of those patients, 22 were in complete remission and agreed to continue; they began a tapering phase that started with receiving concurrent treatment with 15 mg/week of oral methotrexate then, after 12 weeks on methotrexate, discontinued their golimumab but continued on the methotrexate regimen.

After an average follow-up of 80 weeks in this postextension phase, 5 patients (23%) remained in remission on methotrexate monotherapy, while the other 17 patients (77%) had to restart golimumab. Of these 17 patients, 15 because of a relapse, and 2 restarted because they had to discontinue methotrexate after developing adverse effects. The median time to restarting golimumab among these 17 patients was 228 days, Dr. Carron said. In all 17 patients, remission returned within 12 weeks of restarting golimumab treatment.

[email protected]

SOURCE: Carron P et al. EULAR 2018 Congress, Abstract OP0335.

AMSTERDAM – Starting patients with newly diagnosed, peripheral spondyloarthritis (SpA) on treatment with a tumor necrosis factor (TNF) inhibitor within 12 weeks of symptom onset produced an “amazing,” long-term, complete remission that resembled cure in more than half of the 40 treated patients, a finding that now needs replication in a larger, multicenter study, Philippe Carron, MD, said at the European Congress of Rheumatology.

Ongoing research on patients in the original study cohort also showed that methotrexate is largely ineffective to help wean patients in remission on a tumor necrosis factor inhibitor off the biologic drug, said Dr. Carron, a rheumatologist at the University of Ghent (Belgium). In his group’s most recent experience with 22 patients in remission on a regimen of golimumab and methotrexate, 5 remained in remission (23%) when golimumab treatment stopped, whereas the other 17 patients had to restart golimumab (Simponi) while continuing on methotrexate after relapsing on methotrexate monotherapy, Dr. Carron reported.

Mitchel L. Zoler/MDedge News

Methotrexate has “overall weak efficacy for maintaining biological-free remission” in patients with peripheral SpA, he concluded.

But Dr. Carron remained very positive about the main finding of the CRESPA (Clinical Remission in Patients with Early Peripheral Spondyloarthritis) study, which has now shown a durable complete remission – free from arthritis, enthesitis, and dactylitis – in 21 of 40 (53%) patients who began golimumab treatment within 12 weeks of their symptom onset and then remained in remission when the golimumab was eventually stopped. These patients have now remained in complete remission for 2.4-5.8 years of follow-up, Dr. Carron said. He attributed this very durable remission while off any treatment to the rapid start of TNF-inhibitor therapy within weeks of their symptom onset.

“This is fantastic; these patients are cured. Early treatment is the most important reason why the result is so good,” but it also poses the biggest challenge for using this approach in routine practice, Dr. Carron said in an interview. “It took us 3 years to find the 60 patients” enrolled in CRESPA. “Most of the time, patients go elsewhere for treatment, and it’s several months until they see us. In many countries there are not enough rheumatologists, and patients wait 3, 4 months before we see them.” Another important feature of the intervention was that golimumab treatment continued until patients presented as completely symptom free on two consecutive clinic visits spaced about 12 weeks apart.

Dr. Carron and his associates published their initial findings from CRESPA in 2017 (Ann Rheum Dis. 2017 Aug;76[8]:1389-95), and they also have reported updates on the main results at meetings. At the 2018 EULAR Congress, Dr. Carron reported the outcomes of 31 patients in the study who entered a 2-year period of extended golimumab treatment either because they never reached complete remission or because they relapsed after stopping golimumab and so restarted the drug. Of these patients, 25 completed the full 2 years of the CRESPA extension phase on golimumab. Of those patients, 22 were in complete remission and agreed to continue; they began a tapering phase that started with receiving concurrent treatment with 15 mg/week of oral methotrexate then, after 12 weeks on methotrexate, discontinued their golimumab but continued on the methotrexate regimen.

After an average follow-up of 80 weeks in this postextension phase, 5 patients (23%) remained in remission on methotrexate monotherapy, while the other 17 patients (77%) had to restart golimumab. Of these 17 patients, 15 because of a relapse, and 2 restarted because they had to discontinue methotrexate after developing adverse effects. The median time to restarting golimumab among these 17 patients was 228 days, Dr. Carron said. In all 17 patients, remission returned within 12 weeks of restarting golimumab treatment.

[email protected]

SOURCE: Carron P et al. EULAR 2018 Congress, Abstract OP0335.

Higher cardiorespiratory fitness at midlife appears linked to a lower risk of depression in later life. In addition, higher midlife fitness is associated with a lower risk of cardiovascular mortality when depression preceded CVD death, according to a retrospective study published in JAMA Psychiatry.

“These findings ... should encourage physicians to consider fitness and physical activity in promoting healthy aging,” wrote Benjamin L. Willis, MD, MPH, of the Cooper Institute in Dallas, and his associates.

The study included 17,989 participants from the Cooper Center Longitudinal Study and linked data from those participants with a depression diagnosis based on Medicare claims and cardiovascular disease (CVD) mortality rates based on the National Death Index.

The participants were mostly men (80.2%), and their mean age at midlife assessment was 50 years. The participants’ treadmill time at midlife was used to categorize them into age- and sex-specific quintiles, with quintile 1 representing low fitness, quintiles 2 and 3 representing moderate fitness, and quintiles 4 and 5 representing high fitness.

After 117,218 person-years of follow-up, the investigators observed 2,701 depression diagnoses, 610 deaths tied to cardiovascular disease without prior depression, and 231 deaths associated with CVD after depression.

In addition, Dr. Willis and his associates found that participants with a high level of fitness in midlife had a 16% lower risk of depression (hazard ratio, 0.84; 95% confidence interval, 0.74-0.95), compared with participants with a low level of fitness. Participants with a high level of fitness also had a 61% lower risk of death from CVD without depression (HR, 0.39; 95% CI, 0.31-0.48), compared with those who had low fitness levels. Participants with a high fitness level who received a depression diagnosis had a 56% lower risk of death from CVD (HR, 0.44; 95% CI, 0.31-0.64), compared with those who had a low level of fitness.

The researchers pointed out that cardiovascular disease mortality is higher following depression but that cardiorespiratory fitness at midlife is a modifiable risk factor for both depression and CVD mortality.

Dr. Willis and his associates cited several limitations. Among them was the unavailability of information about participants’ use of medication that could influence either the presence or absence of a depression diagnosis.

Nevertheless, they said, the results provide lessons for clinicians and patients.

“This study shows that being fit at midlife is associated with a lower risk of later-life depression and subsequent CVD mortality, even in the presence of depression,” they wrote. “These findings suggest the importance of fitness in primary prevention of heart disease and associated CVD mortality in older aging adults.”

The investigators reported no conflicts of interest.

[email protected]

SOURCE: Willis BL et al. JAMA Psychiatry. 2018 Jun 27. doi: 10.1001/jamapsychiatry.2018.1467.

Higher cardiorespiratory fitness at midlife appears linked to a lower risk of depression in later life. In addition, higher midlife fitness is associated with a lower risk of cardiovascular mortality when depression preceded CVD death, according to a retrospective study published in JAMA Psychiatry.

“These findings ... should encourage physicians to consider fitness and physical activity in promoting healthy aging,” wrote Benjamin L. Willis, MD, MPH, of the Cooper Institute in Dallas, and his associates.

The study included 17,989 participants from the Cooper Center Longitudinal Study and linked data from those participants with a depression diagnosis based on Medicare claims and cardiovascular disease (CVD) mortality rates based on the National Death Index.

The participants were mostly men (80.2%), and their mean age at midlife assessment was 50 years. The participants’ treadmill time at midlife was used to categorize them into age- and sex-specific quintiles, with quintile 1 representing low fitness, quintiles 2 and 3 representing moderate fitness, and quintiles 4 and 5 representing high fitness.

After 117,218 person-years of follow-up, the investigators observed 2,701 depression diagnoses, 610 deaths tied to cardiovascular disease without prior depression, and 231 deaths associated with CVD after depression.

In addition, Dr. Willis and his associates found that participants with a high level of fitness in midlife had a 16% lower risk of depression (hazard ratio, 0.84; 95% confidence interval, 0.74-0.95), compared with participants with a low level of fitness. Participants with a high level of fitness also had a 61% lower risk of death from CVD without depression (HR, 0.39; 95% CI, 0.31-0.48), compared with those who had low fitness levels. Participants with a high fitness level who received a depression diagnosis had a 56% lower risk of death from CVD (HR, 0.44; 95% CI, 0.31-0.64), compared with those who had a low level of fitness.

The researchers pointed out that cardiovascular disease mortality is higher following depression but that cardiorespiratory fitness at midlife is a modifiable risk factor for both depression and CVD mortality.

Dr. Willis and his associates cited several limitations. Among them was the unavailability of information about participants’ use of medication that could influence either the presence or absence of a depression diagnosis.

Nevertheless, they said, the results provide lessons for clinicians and patients.

“This study shows that being fit at midlife is associated with a lower risk of later-life depression and subsequent CVD mortality, even in the presence of depression,” they wrote. “These findings suggest the importance of fitness in primary prevention of heart disease and associated CVD mortality in older aging adults.”

The investigators reported no conflicts of interest.

[email protected]

SOURCE: Willis BL et al. JAMA Psychiatry. 2018 Jun 27. doi: 10.1001/jamapsychiatry.2018.1467.

Higher cardiorespiratory fitness at midlife appears linked to a lower risk of depression in later life. In addition, higher midlife fitness is associated with a lower risk of cardiovascular mortality when depression preceded CVD death, according to a retrospective study published in JAMA Psychiatry.

“These findings ... should encourage physicians to consider fitness and physical activity in promoting healthy aging,” wrote Benjamin L. Willis, MD, MPH, of the Cooper Institute in Dallas, and his associates.

The study included 17,989 participants from the Cooper Center Longitudinal Study and linked data from those participants with a depression diagnosis based on Medicare claims and cardiovascular disease (CVD) mortality rates based on the National Death Index.

The participants were mostly men (80.2%), and their mean age at midlife assessment was 50 years. The participants’ treadmill time at midlife was used to categorize them into age- and sex-specific quintiles, with quintile 1 representing low fitness, quintiles 2 and 3 representing moderate fitness, and quintiles 4 and 5 representing high fitness.

After 117,218 person-years of follow-up, the investigators observed 2,701 depression diagnoses, 610 deaths tied to cardiovascular disease without prior depression, and 231 deaths associated with CVD after depression.

In addition, Dr. Willis and his associates found that participants with a high level of fitness in midlife had a 16% lower risk of depression (hazard ratio, 0.84; 95% confidence interval, 0.74-0.95), compared with participants with a low level of fitness. Participants with a high level of fitness also had a 61% lower risk of death from CVD without depression (HR, 0.39; 95% CI, 0.31-0.48), compared with those who had low fitness levels. Participants with a high fitness level who received a depression diagnosis had a 56% lower risk of death from CVD (HR, 0.44; 95% CI, 0.31-0.64), compared with those who had a low level of fitness.

The researchers pointed out that cardiovascular disease mortality is higher following depression but that cardiorespiratory fitness at midlife is a modifiable risk factor for both depression and CVD mortality.

Dr. Willis and his associates cited several limitations. Among them was the unavailability of information about participants’ use of medication that could influence either the presence or absence of a depression diagnosis.

Nevertheless, they said, the results provide lessons for clinicians and patients.

“This study shows that being fit at midlife is associated with a lower risk of later-life depression and subsequent CVD mortality, even in the presence of depression,” they wrote. “These findings suggest the importance of fitness in primary prevention of heart disease and associated CVD mortality in older aging adults.”

The investigators reported no conflicts of interest.

[email protected]

SOURCE: Willis BL et al. JAMA Psychiatry. 2018 Jun 27. doi: 10.1001/jamapsychiatry.2018.1467.

AMSTERDAM – Results of the IMAGINE-RA study show no added benefit of using magnetic resonance imaging as part of a treat-to-target strategy for rheumatoid arthritis.

Sara Freeman/MDedge News

What was not known, however, was whether there was any value in specifically targeting MRI remission in patients who had already achieved clinical remission. This is what the IMAGINE-RA study set out to address. It was a 2-year trial of 200 patients with rheumatoid arthritis in clinical remission who were recruited and randomized to either an MRI or conventional treat-to-target strategy. The study involved nine rheumatology and eight radiological departments, Dr. Møller-Bisgaard said.

The protocol for the study (Trials. 2015;16:178) defined clinical remission as a DAS28-CRP of 3.2 or lower and no swollen joints. Patients had to have erosions on x-ray, be anti–cyclic citrullinated peptide positive, and be treated only with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) at the time of entry.

During the study patients were assessed every 4 months via the DAS28 or DAS28 plus MRI of the dominant hand and wrist, with radiographs of the hands and feet performed annually in both groups and MRI also performed yearly in the conventional treat-to-target group.

“Treatment was intensified in both arms if the DAS28-CRP was above 3.2, and there was at least one clinical swollen joint,” Dr. Møller-Bisgaard explained. Treatment was also intensified in the MRI group if bone marrow edema was observed. Treatment intensification involved maximal doses of csDMARDs alone or in combinations, and then addition of biologic treatments, such as a tumor necrosis factor inhibitor.

“Targeting absence of MRI bone marrow edema in addition to a conventional treat-to-target strategy in RA patients in clinical remission had no effect on the probability of achieving DAS28-CRP remission or halting radiographic progression,” she said.

However, there were some positive effects on several predefined secondary endpoints. For instance, more patients in the MRI group than in the conventional treat-to-target group achieved American College of Rheumatology/EULAR remission (49% vs. 32%; P = .017). There was a significant improvement in the number of swollen joints and a patient and physician global assessment. “There was also more improvement in HAQ [Health Assessment Questionnaire], with a difference between the groups of .14 [P less than .001], Dr. Møller-Bisgaard reported.

SOURCE: Møller-Bisgaard S et al. EULAR 2018 Congress. Abstract OP0018.

AMSTERDAM – Results of the IMAGINE-RA study show no added benefit of using magnetic resonance imaging as part of a treat-to-target strategy for rheumatoid arthritis.

Sara Freeman/MDedge News

What was not known, however, was whether there was any value in specifically targeting MRI remission in patients who had already achieved clinical remission. This is what the IMAGINE-RA study set out to address. It was a 2-year trial of 200 patients with rheumatoid arthritis in clinical remission who were recruited and randomized to either an MRI or conventional treat-to-target strategy. The study involved nine rheumatology and eight radiological departments, Dr. Møller-Bisgaard said.

The protocol for the study (Trials. 2015;16:178) defined clinical remission as a DAS28-CRP of 3.2 or lower and no swollen joints. Patients had to have erosions on x-ray, be anti–cyclic citrullinated peptide positive, and be treated only with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) at the time of entry.

During the study patients were assessed every 4 months via the DAS28 or DAS28 plus MRI of the dominant hand and wrist, with radiographs of the hands and feet performed annually in both groups and MRI also performed yearly in the conventional treat-to-target group.

“Treatment was intensified in both arms if the DAS28-CRP was above 3.2, and there was at least one clinical swollen joint,” Dr. Møller-Bisgaard explained. Treatment was also intensified in the MRI group if bone marrow edema was observed. Treatment intensification involved maximal doses of csDMARDs alone or in combinations, and then addition of biologic treatments, such as a tumor necrosis factor inhibitor.

“Targeting absence of MRI bone marrow edema in addition to a conventional treat-to-target strategy in RA patients in clinical remission had no effect on the probability of achieving DAS28-CRP remission or halting radiographic progression,” she said.

However, there were some positive effects on several predefined secondary endpoints. For instance, more patients in the MRI group than in the conventional treat-to-target group achieved American College of Rheumatology/EULAR remission (49% vs. 32%; P = .017). There was a significant improvement in the number of swollen joints and a patient and physician global assessment. “There was also more improvement in HAQ [Health Assessment Questionnaire], with a difference between the groups of .14 [P less than .001], Dr. Møller-Bisgaard reported.

SOURCE: Møller-Bisgaard S et al. EULAR 2018 Congress. Abstract OP0018.

AMSTERDAM – Results of the IMAGINE-RA study show no added benefit of using magnetic resonance imaging as part of a treat-to-target strategy for rheumatoid arthritis.

Sara Freeman/MDedge News

What was not known, however, was whether there was any value in specifically targeting MRI remission in patients who had already achieved clinical remission. This is what the IMAGINE-RA study set out to address. It was a 2-year trial of 200 patients with rheumatoid arthritis in clinical remission who were recruited and randomized to either an MRI or conventional treat-to-target strategy. The study involved nine rheumatology and eight radiological departments, Dr. Møller-Bisgaard said.

The protocol for the study (Trials. 2015;16:178) defined clinical remission as a DAS28-CRP of 3.2 or lower and no swollen joints. Patients had to have erosions on x-ray, be anti–cyclic citrullinated peptide positive, and be treated only with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) at the time of entry.

During the study patients were assessed every 4 months via the DAS28 or DAS28 plus MRI of the dominant hand and wrist, with radiographs of the hands and feet performed annually in both groups and MRI also performed yearly in the conventional treat-to-target group.

“Treatment was intensified in both arms if the DAS28-CRP was above 3.2, and there was at least one clinical swollen joint,” Dr. Møller-Bisgaard explained. Treatment was also intensified in the MRI group if bone marrow edema was observed. Treatment intensification involved maximal doses of csDMARDs alone or in combinations, and then addition of biologic treatments, such as a tumor necrosis factor inhibitor.

“Targeting absence of MRI bone marrow edema in addition to a conventional treat-to-target strategy in RA patients in clinical remission had no effect on the probability of achieving DAS28-CRP remission or halting radiographic progression,” she said.

However, there were some positive effects on several predefined secondary endpoints. For instance, more patients in the MRI group than in the conventional treat-to-target group achieved American College of Rheumatology/EULAR remission (49% vs. 32%; P = .017). There was a significant improvement in the number of swollen joints and a patient and physician global assessment. “There was also more improvement in HAQ [Health Assessment Questionnaire], with a difference between the groups of .14 [P less than .001], Dr. Møller-Bisgaard reported.

SOURCE: Møller-Bisgaard S et al. EULAR 2018 Congress. Abstract OP0018.

SAN DIEGO – Less than 30% of veterans on medication-assisted treatment for opioids had a diagnosis of opioid use disorder, and only 7% of veterans with an opioid use disorder initiated medication-assisted treatment.

Doug Brunk/MDedge News

Those are key findings from a large study that set out to assess factors associated with initiating medication-assisted treatment (MAT) among veterans seeking pain care and to characterize the cohort of veterans seeking specialty pain care who initiated MAT.

“You would expect that the percentage of people who are receiving medication-assisted treatment for opioid use disorder would be high, but it was really low,” lead study author Lisham Ashrafioun, PhD, said in an interview at the annual meeting of the College on Problems of Drug Dependence. “These findings are preliminary, but I think we need to understand a lot more about how to treat people with opioid use disorders who are receiving pain care as well.”

Dr. Ashrafioun, a research investigator at the Veteran Affairs Center of Excellence for Suicide Prevention at the Canandaigua VA Medical Center, N.Y., and his associates drew from national VA electronic medical record data to identify 219,443 veterans who initiated specialty pain services during fiscal year 2012-2014. They used procedure and billing codes to identify veterans who started using MAT for opioids within the year following initiation of pain services, and extracted data on demographics, psychiatric and medical diagnoses, and pain intensity scores.

Of the 219,443 veterans, only 2,406 had received MAT in the year following the index visit (1.1%). In addition, only 26.4% of those on MAT had an opioid use disorder and just 6.6% of those with an opioid use disorder initiated MAT.

In adjusted analyses, opioid use disorders (adjusted odds ratio, 5.71) and opioid prescriptions (aOR, 2.33) were significantly associated with greater odds of receiving MAT. Moreover, having a diagnosis of depression was associated with a greater odds of receiving MAT (aOR, 1.26), while having a diagnosis of PTSD was associated with a greater odds of not receiving it (aOR, 0.90). The researchers also found that having a diagnosis of alcohol use disorder was associated with a greater odds of not receiving MAT (aOR, 0.85), while having a diagnosis of drug use disorder was associated with a greater odds of receiving it (aOR, 1.32).

Dr. Ashrafioun, who also holds a faculty position in the department of psychiatry at the University of Rochester (N.Y.), acknowledged certain limitations of the study. For example, the sample was restricted to only those receiving specialty pain care, provider and facility variation was not accounted for, and study participants might have initiated MAT outside of the VA.

He reported having no financial disclosures.

[email protected]

SAN DIEGO – Less than 30% of veterans on medication-assisted treatment for opioids had a diagnosis of opioid use disorder, and only 7% of veterans with an opioid use disorder initiated medication-assisted treatment.

Doug Brunk/MDedge News

Those are key findings from a large study that set out to assess factors associated with initiating medication-assisted treatment (MAT) among veterans seeking pain care and to characterize the cohort of veterans seeking specialty pain care who initiated MAT.

“You would expect that the percentage of people who are receiving medication-assisted treatment for opioid use disorder would be high, but it was really low,” lead study author Lisham Ashrafioun, PhD, said in an interview at the annual meeting of the College on Problems of Drug Dependence. “These findings are preliminary, but I think we need to understand a lot more about how to treat people with opioid use disorders who are receiving pain care as well.”

Dr. Ashrafioun, a research investigator at the Veteran Affairs Center of Excellence for Suicide Prevention at the Canandaigua VA Medical Center, N.Y., and his associates drew from national VA electronic medical record data to identify 219,443 veterans who initiated specialty pain services during fiscal year 2012-2014. They used procedure and billing codes to identify veterans who started using MAT for opioids within the year following initiation of pain services, and extracted data on demographics, psychiatric and medical diagnoses, and pain intensity scores.

Of the 219,443 veterans, only 2,406 had received MAT in the year following the index visit (1.1%). In addition, only 26.4% of those on MAT had an opioid use disorder and just 6.6% of those with an opioid use disorder initiated MAT.

In adjusted analyses, opioid use disorders (adjusted odds ratio, 5.71) and opioid prescriptions (aOR, 2.33) were significantly associated with greater odds of receiving MAT. Moreover, having a diagnosis of depression was associated with a greater odds of receiving MAT (aOR, 1.26), while having a diagnosis of PTSD was associated with a greater odds of not receiving it (aOR, 0.90). The researchers also found that having a diagnosis of alcohol use disorder was associated with a greater odds of not receiving MAT (aOR, 0.85), while having a diagnosis of drug use disorder was associated with a greater odds of receiving it (aOR, 1.32).

Dr. Ashrafioun, who also holds a faculty position in the department of psychiatry at the University of Rochester (N.Y.), acknowledged certain limitations of the study. For example, the sample was restricted to only those receiving specialty pain care, provider and facility variation was not accounted for, and study participants might have initiated MAT outside of the VA.

He reported having no financial disclosures.

[email protected]

SAN DIEGO – Less than 30% of veterans on medication-assisted treatment for opioids had a diagnosis of opioid use disorder, and only 7% of veterans with an opioid use disorder initiated medication-assisted treatment.

Doug Brunk/MDedge News

Those are key findings from a large study that set out to assess factors associated with initiating medication-assisted treatment (MAT) among veterans seeking pain care and to characterize the cohort of veterans seeking specialty pain care who initiated MAT.

“You would expect that the percentage of people who are receiving medication-assisted treatment for opioid use disorder would be high, but it was really low,” lead study author Lisham Ashrafioun, PhD, said in an interview at the annual meeting of the College on Problems of Drug Dependence. “These findings are preliminary, but I think we need to understand a lot more about how to treat people with opioid use disorders who are receiving pain care as well.”

Dr. Ashrafioun, a research investigator at the Veteran Affairs Center of Excellence for Suicide Prevention at the Canandaigua VA Medical Center, N.Y., and his associates drew from national VA electronic medical record data to identify 219,443 veterans who initiated specialty pain services during fiscal year 2012-2014. They used procedure and billing codes to identify veterans who started using MAT for opioids within the year following initiation of pain services, and extracted data on demographics, psychiatric and medical diagnoses, and pain intensity scores.

Of the 219,443 veterans, only 2,406 had received MAT in the year following the index visit (1.1%). In addition, only 26.4% of those on MAT had an opioid use disorder and just 6.6% of those with an opioid use disorder initiated MAT.

In adjusted analyses, opioid use disorders (adjusted odds ratio, 5.71) and opioid prescriptions (aOR, 2.33) were significantly associated with greater odds of receiving MAT. Moreover, having a diagnosis of depression was associated with a greater odds of receiving MAT (aOR, 1.26), while having a diagnosis of PTSD was associated with a greater odds of not receiving it (aOR, 0.90). The researchers also found that having a diagnosis of alcohol use disorder was associated with a greater odds of not receiving MAT (aOR, 0.85), while having a diagnosis of drug use disorder was associated with a greater odds of receiving it (aOR, 1.32).

Dr. Ashrafioun, who also holds a faculty position in the department of psychiatry at the University of Rochester (N.Y.), acknowledged certain limitations of the study. For example, the sample was restricted to only those receiving specialty pain care, provider and facility variation was not accounted for, and study participants might have initiated MAT outside of the VA.

He reported having no financial disclosures.

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