Among men younger than 65 with prostate cancer, proton beam radiotherapy (PBT) was associated with significantly lower rates of urinary toxicities than was intensity-modulated radiotherapy (IMRT), but this safety advantage came at the cost of nearly $60,000 extra per patient, results of an insurance claims study show.

The rate of a composite of urinary toxicities at 2 years among 693 men treated with PBT was 33%, compared with 42% for 3,465 men matched by propensity score who were treated with IMRT. Respective rates of erectile dysfunction were 21% vs. 28%. The mean cost for PBT, however, was nearly double that for IMRT, reported Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues.

Although PBT was better at sparing patients from urinary toxicities, it was associated with increased bowel toxicities, and a second comparison of IMRT with stereotactic body radiotherapy (SBRT) showed that SBRT, while slightly cheaper than IMRT, was associated with modest increases in some urinary toxicities, the researchers reported in a study published online in the Journal of Clinical Oncology.

“These key findings, coupled with the real-world private insurance cost reported herein, will be useful for patients selecting the most appropriate treatment and for researchers designing cost-effectiveness models to guide treatment decisions in prostate cancer,” they wrote.

The investigators combed through the MarketScan Commercial Claims and Encounters database to identify men who underwent radiation therapy for prostate cancer between 2008 and 2015. They used propensity-score matching, a technique designed to even out potential confounding factors, to compare those treated with IMRT with others treated with PBT or SBRT.

As noted, PBT was associated with significantly lower urinary toxicities and erectile dysfunction compared with IMRT (P less than .001 for each comparison), but with a higher rate of bowel toxicities at 2 years (20% vs. 15%, P = .02).

The mean cost per patient in 2015 dollars for PBT was $115,501, compared with $59,012 for IMRT.

SOURCE: Smith BD et al. J Clin Oncol. 2018 Mar 21. doi: 10.1200/JCO.2017.75.5371.

Among men younger than 65 with prostate cancer, proton beam radiotherapy (PBT) was associated with significantly lower rates of urinary toxicities than was intensity-modulated radiotherapy (IMRT), but this safety advantage came at the cost of nearly $60,000 extra per patient, results of an insurance claims study show.

The rate of a composite of urinary toxicities at 2 years among 693 men treated with PBT was 33%, compared with 42% for 3,465 men matched by propensity score who were treated with IMRT. Respective rates of erectile dysfunction were 21% vs. 28%. The mean cost for PBT, however, was nearly double that for IMRT, reported Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues.

Although PBT was better at sparing patients from urinary toxicities, it was associated with increased bowel toxicities, and a second comparison of IMRT with stereotactic body radiotherapy (SBRT) showed that SBRT, while slightly cheaper than IMRT, was associated with modest increases in some urinary toxicities, the researchers reported in a study published online in the Journal of Clinical Oncology.

“These key findings, coupled with the real-world private insurance cost reported herein, will be useful for patients selecting the most appropriate treatment and for researchers designing cost-effectiveness models to guide treatment decisions in prostate cancer,” they wrote.

The investigators combed through the MarketScan Commercial Claims and Encounters database to identify men who underwent radiation therapy for prostate cancer between 2008 and 2015. They used propensity-score matching, a technique designed to even out potential confounding factors, to compare those treated with IMRT with others treated with PBT or SBRT.

As noted, PBT was associated with significantly lower urinary toxicities and erectile dysfunction compared with IMRT (P less than .001 for each comparison), but with a higher rate of bowel toxicities at 2 years (20% vs. 15%, P = .02).

The mean cost per patient in 2015 dollars for PBT was $115,501, compared with $59,012 for IMRT.

SOURCE: Smith BD et al. J Clin Oncol. 2018 Mar 21. doi: 10.1200/JCO.2017.75.5371.

Among men younger than 65 with prostate cancer, proton beam radiotherapy (PBT) was associated with significantly lower rates of urinary toxicities than was intensity-modulated radiotherapy (IMRT), but this safety advantage came at the cost of nearly $60,000 extra per patient, results of an insurance claims study show.

The rate of a composite of urinary toxicities at 2 years among 693 men treated with PBT was 33%, compared with 42% for 3,465 men matched by propensity score who were treated with IMRT. Respective rates of erectile dysfunction were 21% vs. 28%. The mean cost for PBT, however, was nearly double that for IMRT, reported Benjamin D. Smith, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues.

Although PBT was better at sparing patients from urinary toxicities, it was associated with increased bowel toxicities, and a second comparison of IMRT with stereotactic body radiotherapy (SBRT) showed that SBRT, while slightly cheaper than IMRT, was associated with modest increases in some urinary toxicities, the researchers reported in a study published online in the Journal of Clinical Oncology.

“These key findings, coupled with the real-world private insurance cost reported herein, will be useful for patients selecting the most appropriate treatment and for researchers designing cost-effectiveness models to guide treatment decisions in prostate cancer,” they wrote.

The investigators combed through the MarketScan Commercial Claims and Encounters database to identify men who underwent radiation therapy for prostate cancer between 2008 and 2015. They used propensity-score matching, a technique designed to even out potential confounding factors, to compare those treated with IMRT with others treated with PBT or SBRT.

As noted, PBT was associated with significantly lower urinary toxicities and erectile dysfunction compared with IMRT (P less than .001 for each comparison), but with a higher rate of bowel toxicities at 2 years (20% vs. 15%, P = .02).

The mean cost per patient in 2015 dollars for PBT was $115,501, compared with $59,012 for IMRT.

SOURCE: Smith BD et al. J Clin Oncol. 2018 Mar 21. doi: 10.1200/JCO.2017.75.5371.

MAUI, HAWAII – Prolonged corticosteroid therapy for inflammatory bowel disease (IBD) was associated with a significantly increased mortality risk compared with anti–tumor necrosis factor therapy in a landmark study spotlighted by Edward V. Loftus Jr., MD, at the Gastroenterology Updates, IBD, Liver Disease meeting.

This was one of several key studies on safety issues involving IBD medications published in the past year. Others highlighted by Dr. Loftus and copanelist William J. Sandborn, MD, included a study that provided persuasive evidence that TNF inhibitors modestly increase lymphoma risk in IBD patients to a degree similar to that of thiopurines, and several reports addressing the question of whether preoperative use of vedolizumab in patients undergoing major abdominal operations for IBD boosts postoperative infection risk.
 

Mortality impact of prolonged steroids vs. anti-TNF therapy

Bruce Jancin/MDedge News

That will come as an unpleasant surprise to many physicians. There is a widespread reluctance to turn to continuous chronic immunosuppression via anti-TNF therapy in patients with challenging IBD, particularly in elderly individuals with multiple comorbid conditions. Many physicians have heard and read so much about the biologics’ risks of serious adverse events that they opt instead for multiple courses of corticosteroids for disease control. This is a serious mistake, emphasized Dr. Loftus, professor of medicine and director of the IBD Interest Group at the Mayo Clinic in Rochester, Minn.

“When you say, ‘Oh, I’ll just give that patient another prednisone taper, he doesn’t want to start taking a TNF inhibitor,’ you’re actually doing the patient harm. You’re actually affecting the patient’s life expectancy when you do that,” he declared. “The message is, yes, steroids are cheap, steroids are easy, nobody’s afraid of steroids, but you should be afraid of steroids.”

The 1,879 Crohn’s disease patients who entered the cohort as new users of anti-TNF therapy had a subsequent mortality incidence rate of 21.4 per 1,000 person-years, compared with a rate of 30.1 per 1,000 person-years in the 7,694 who entered the study period as prolonged steroid users. In a multivariate analysis accounting for 57 potential confounding factors, this translated to a highly significant 22% relative risk reduction in mortality in the patients who went with anti-TNF therapy (Am J Gastroenterol. 2018 Jan 16. doi: 10.1038/ajg.2017.479).

A similar trend was seen in the ulcerative colitis cohort. The 459 ulcerative colitis patients who entered the cohort as new anti-TNF therapy users had a mortality incidence rate of 23.0 per 1,000 person-years, compared with a rate of 30.9 in the 3,224 who received more than 3,000 mg of prednisone in the next 12 months. This represented a 14% relative risk reduction, although this favorable trend did not achieve statistical significance, perhaps because of the smaller size of the ulcerative colitis cohort.

In addition to demonstrably greater life expectancy, anti-TNF therapy offered additional benefits: a 32% reduction in the risk of major adverse cardiovascular events and a 46% lower incidence of hip fracture.

Dr. Sandborn, professor of medicine and chief of the division of gastroenterology at the University of California, San Diego, spun the study data another way: “It shows the number needed to kill is 33. So for every 33 patients you put on prolonged corticosteroids, you’re killing one extra patient by doing that. Of course, you probably blame it on their age and comorbidities, but this is it. This is the data.”

TNF blockers, thiopurines, and lymphoma

The use of thiopurines for treatment of IBD is widely recognized to be associated with a small but real increased risk of lymphoma. Now a large French national study has demonstrated for the first time that anti-TNF therapy for IBD is also associated with an increased risk that needs to be discussed with patients. And in IBD patients on combination therapy with both classes of medication, that risk jumps to 6.1-fold greater than in unexposed IBD patients (JAMA 2017 Nov 7;318[17]:1679-86).

Dr. Loftus and Dr. Sandborn urged their colleagues to keep this increased risk in perspective in counseling patients by focusing on the modest absolute increase in risk rather than the scarier-sounding relative risk. Notably, two-thirds of lymphomas in the French study occurred in patients not on thiopurines or anti-TNF agents.

“The most interesting thing to me is that we worry and worry about lymphoma, and guess what? In this study and in multiple other studies, the majority of lymphomas occurring in IBD patients have nothing to do with their medications. They’re due to the usual risk factors for lymphoma, which include age and male gender,” Dr. Loftus observed.

The French study included more than 189,000 IBD patients followed for a median of 6.7 years, during which 336 cases of lymphoma occurred. The incidence rate was 0.26 cases per 1,000 person-years in unexposed patients. The rate was significantly higher at 0.54 per 1,000 person-years in those on thiopurine monotherapy, increased to a similar extent at 0.41 cases per 1,000 person-years in patients on anti-TNF monotherapy, and 0.95 per 1,000 person-years in those on combination therapy.

In a multivariate analysis, the lymphoma risk was an adjusted 2.6-fold greater in patients exposed to thiopurine monotherapy than in unexposed patients, 2.41-fold greater in patients exposed to anti-TNF monotherapy, and 6.1-fold greater in those exposed to combination therapy.

“The point I want to make is the lymphoma rates in the thiopurine monotherapy and anti-TNF monotherapy groups are not significantly different. So the claim that’s been out there that the increased lymphoma risk in IBD patients can be completely explained by thiopurines is wrong. This study is showing us that with anti-TNF monotherapy there is still a low-level risk of lymphoma,” Dr. Loftus said.

“It is somewhat eyebrow-raising when you see that relative risk of 6.1, and that’s what patients are going to focus on, but when you counsel patients you have to redirect them to the absolute risk. You can say, ‘Even on combination therapy, your risk is 1 in 1,000,’ ” the gastroenterologist said.

Dr. Sandborn said the lymphoma signal hadn’t been spotted previously because the individual registries of IBD patients on anti-TNF agents are too small to allow for identification of a small increase in risk. The French investigators overcame that limitation by tapping into the country’s national health care system.

“This is a huge dataset and I think the message is unequivocal,” Dr. Sandborn said.

Preoperative vedolizumab and postoperative infection risk

“The overall safety profile of vedolizumab is pretty good,” Dr. Loftus observed. “The one unanswered question is its safety when used within 8-12 weeks of a major abdominal operation.”

It’s a clinically relevant question because vedolizumab selectively inhibits leukocyte migration into the intestinal tract, which could provide a mechanism for impaired postoperative wound healing in patients undergoing major abdominal surgery. And sooner or later a high proportion of IBD patients have a major abdominal operation.

Dr. Loftus and his coinvestigators kicked off a controversy by reporting a 37% incidence of surgical site infections in IBD patients who received vedolizumab within 30 days of a major abdominal operation in a retrospective chart review of the Mayo Clinic experience, a postoperative infection rate strikingly higher than in their patients on anti-TNF or nonbiologic therapy (J Crohns Colitis. 2017 Feb;11[2]:185-90).

This prompted investigators at the University of Chicago to look retrospectively at their institutional experience. They reported no increased risk in IBD patients on vedolizumab (Am J Gastroenterol. 2017 Sep;112[9]:1423-9). Neither did Belgian gastroenterologists at the Catholic University of Leuven (J Crohns Colitis. 2017 Oct 27;11[11]:1353-61).

Most recently, the Mayo Clinic group along with gastroenterologists at three other U.S. centers collaborated in a multicenter retrospective review of 146 adult IBD patients who received vedolizumab within 12 weeks before major abdominal surgery and 289 who received anti-TNF therapy. In a multivariate analysis, perioperative use of vedolizumab was independently associated with a 5.8-fold increased risk of developing a surgical site infection (J Inflamm Bowel Dis. 2018 Mar 19. doi: 10.1093/ibd/izx076).

Dr. Sandborn, who like Dr. Loftus was a coauthor of the multicenter study, drew back to look at the big picture.

“Is vedolizumab really causal? I doubt it, although it’s remotely possible. But I bet vedolizumab therapy is a really good marker for sick patients, and sick patients have worse operative outcomes, so we ought to be conservative with their surgery. My read of this is this [postoperative infection risk] isn’t unique to vedolizumab. Just be careful with sick patients when you’re operating and do more conservative surgeries,” he said.

Both gastroenterologists reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.

bjancin@mdedge.com

MAUI, HAWAII – Prolonged corticosteroid therapy for inflammatory bowel disease (IBD) was associated with a significantly increased mortality risk compared with anti–tumor necrosis factor therapy in a landmark study spotlighted by Edward V. Loftus Jr., MD, at the Gastroenterology Updates, IBD, Liver Disease meeting.

This was one of several key studies on safety issues involving IBD medications published in the past year. Others highlighted by Dr. Loftus and copanelist William J. Sandborn, MD, included a study that provided persuasive evidence that TNF inhibitors modestly increase lymphoma risk in IBD patients to a degree similar to that of thiopurines, and several reports addressing the question of whether preoperative use of vedolizumab in patients undergoing major abdominal operations for IBD boosts postoperative infection risk.
 

Mortality impact of prolonged steroids vs. anti-TNF therapy

Bruce Jancin/MDedge News

That will come as an unpleasant surprise to many physicians. There is a widespread reluctance to turn to continuous chronic immunosuppression via anti-TNF therapy in patients with challenging IBD, particularly in elderly individuals with multiple comorbid conditions. Many physicians have heard and read so much about the biologics’ risks of serious adverse events that they opt instead for multiple courses of corticosteroids for disease control. This is a serious mistake, emphasized Dr. Loftus, professor of medicine and director of the IBD Interest Group at the Mayo Clinic in Rochester, Minn.

“When you say, ‘Oh, I’ll just give that patient another prednisone taper, he doesn’t want to start taking a TNF inhibitor,’ you’re actually doing the patient harm. You’re actually affecting the patient’s life expectancy when you do that,” he declared. “The message is, yes, steroids are cheap, steroids are easy, nobody’s afraid of steroids, but you should be afraid of steroids.”

The 1,879 Crohn’s disease patients who entered the cohort as new users of anti-TNF therapy had a subsequent mortality incidence rate of 21.4 per 1,000 person-years, compared with a rate of 30.1 per 1,000 person-years in the 7,694 who entered the study period as prolonged steroid users. In a multivariate analysis accounting for 57 potential confounding factors, this translated to a highly significant 22% relative risk reduction in mortality in the patients who went with anti-TNF therapy (Am J Gastroenterol. 2018 Jan 16. doi: 10.1038/ajg.2017.479).

A similar trend was seen in the ulcerative colitis cohort. The 459 ulcerative colitis patients who entered the cohort as new anti-TNF therapy users had a mortality incidence rate of 23.0 per 1,000 person-years, compared with a rate of 30.9 in the 3,224 who received more than 3,000 mg of prednisone in the next 12 months. This represented a 14% relative risk reduction, although this favorable trend did not achieve statistical significance, perhaps because of the smaller size of the ulcerative colitis cohort.

In addition to demonstrably greater life expectancy, anti-TNF therapy offered additional benefits: a 32% reduction in the risk of major adverse cardiovascular events and a 46% lower incidence of hip fracture.

Dr. Sandborn, professor of medicine and chief of the division of gastroenterology at the University of California, San Diego, spun the study data another way: “It shows the number needed to kill is 33. So for every 33 patients you put on prolonged corticosteroids, you’re killing one extra patient by doing that. Of course, you probably blame it on their age and comorbidities, but this is it. This is the data.”

TNF blockers, thiopurines, and lymphoma

The use of thiopurines for treatment of IBD is widely recognized to be associated with a small but real increased risk of lymphoma. Now a large French national study has demonstrated for the first time that anti-TNF therapy for IBD is also associated with an increased risk that needs to be discussed with patients. And in IBD patients on combination therapy with both classes of medication, that risk jumps to 6.1-fold greater than in unexposed IBD patients (JAMA 2017 Nov 7;318[17]:1679-86).

Dr. Loftus and Dr. Sandborn urged their colleagues to keep this increased risk in perspective in counseling patients by focusing on the modest absolute increase in risk rather than the scarier-sounding relative risk. Notably, two-thirds of lymphomas in the French study occurred in patients not on thiopurines or anti-TNF agents.

“The most interesting thing to me is that we worry and worry about lymphoma, and guess what? In this study and in multiple other studies, the majority of lymphomas occurring in IBD patients have nothing to do with their medications. They’re due to the usual risk factors for lymphoma, which include age and male gender,” Dr. Loftus observed.

The French study included more than 189,000 IBD patients followed for a median of 6.7 years, during which 336 cases of lymphoma occurred. The incidence rate was 0.26 cases per 1,000 person-years in unexposed patients. The rate was significantly higher at 0.54 per 1,000 person-years in those on thiopurine monotherapy, increased to a similar extent at 0.41 cases per 1,000 person-years in patients on anti-TNF monotherapy, and 0.95 per 1,000 person-years in those on combination therapy.

In a multivariate analysis, the lymphoma risk was an adjusted 2.6-fold greater in patients exposed to thiopurine monotherapy than in unexposed patients, 2.41-fold greater in patients exposed to anti-TNF monotherapy, and 6.1-fold greater in those exposed to combination therapy.

“The point I want to make is the lymphoma rates in the thiopurine monotherapy and anti-TNF monotherapy groups are not significantly different. So the claim that’s been out there that the increased lymphoma risk in IBD patients can be completely explained by thiopurines is wrong. This study is showing us that with anti-TNF monotherapy there is still a low-level risk of lymphoma,” Dr. Loftus said.

“It is somewhat eyebrow-raising when you see that relative risk of 6.1, and that’s what patients are going to focus on, but when you counsel patients you have to redirect them to the absolute risk. You can say, ‘Even on combination therapy, your risk is 1 in 1,000,’ ” the gastroenterologist said.

Dr. Sandborn said the lymphoma signal hadn’t been spotted previously because the individual registries of IBD patients on anti-TNF agents are too small to allow for identification of a small increase in risk. The French investigators overcame that limitation by tapping into the country’s national health care system.

“This is a huge dataset and I think the message is unequivocal,” Dr. Sandborn said.

Preoperative vedolizumab and postoperative infection risk

“The overall safety profile of vedolizumab is pretty good,” Dr. Loftus observed. “The one unanswered question is its safety when used within 8-12 weeks of a major abdominal operation.”

It’s a clinically relevant question because vedolizumab selectively inhibits leukocyte migration into the intestinal tract, which could provide a mechanism for impaired postoperative wound healing in patients undergoing major abdominal surgery. And sooner or later a high proportion of IBD patients have a major abdominal operation.

Dr. Loftus and his coinvestigators kicked off a controversy by reporting a 37% incidence of surgical site infections in IBD patients who received vedolizumab within 30 days of a major abdominal operation in a retrospective chart review of the Mayo Clinic experience, a postoperative infection rate strikingly higher than in their patients on anti-TNF or nonbiologic therapy (J Crohns Colitis. 2017 Feb;11[2]:185-90).

This prompted investigators at the University of Chicago to look retrospectively at their institutional experience. They reported no increased risk in IBD patients on vedolizumab (Am J Gastroenterol. 2017 Sep;112[9]:1423-9). Neither did Belgian gastroenterologists at the Catholic University of Leuven (J Crohns Colitis. 2017 Oct 27;11[11]:1353-61).

Most recently, the Mayo Clinic group along with gastroenterologists at three other U.S. centers collaborated in a multicenter retrospective review of 146 adult IBD patients who received vedolizumab within 12 weeks before major abdominal surgery and 289 who received anti-TNF therapy. In a multivariate analysis, perioperative use of vedolizumab was independently associated with a 5.8-fold increased risk of developing a surgical site infection (J Inflamm Bowel Dis. 2018 Mar 19. doi: 10.1093/ibd/izx076).

Dr. Sandborn, who like Dr. Loftus was a coauthor of the multicenter study, drew back to look at the big picture.

“Is vedolizumab really causal? I doubt it, although it’s remotely possible. But I bet vedolizumab therapy is a really good marker for sick patients, and sick patients have worse operative outcomes, so we ought to be conservative with their surgery. My read of this is this [postoperative infection risk] isn’t unique to vedolizumab. Just be careful with sick patients when you’re operating and do more conservative surgeries,” he said.

Both gastroenterologists reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.

bjancin@mdedge.com

MAUI, HAWAII – Prolonged corticosteroid therapy for inflammatory bowel disease (IBD) was associated with a significantly increased mortality risk compared with anti–tumor necrosis factor therapy in a landmark study spotlighted by Edward V. Loftus Jr., MD, at the Gastroenterology Updates, IBD, Liver Disease meeting.

This was one of several key studies on safety issues involving IBD medications published in the past year. Others highlighted by Dr. Loftus and copanelist William J. Sandborn, MD, included a study that provided persuasive evidence that TNF inhibitors modestly increase lymphoma risk in IBD patients to a degree similar to that of thiopurines, and several reports addressing the question of whether preoperative use of vedolizumab in patients undergoing major abdominal operations for IBD boosts postoperative infection risk.
 

Mortality impact of prolonged steroids vs. anti-TNF therapy

Bruce Jancin/MDedge News

That will come as an unpleasant surprise to many physicians. There is a widespread reluctance to turn to continuous chronic immunosuppression via anti-TNF therapy in patients with challenging IBD, particularly in elderly individuals with multiple comorbid conditions. Many physicians have heard and read so much about the biologics’ risks of serious adverse events that they opt instead for multiple courses of corticosteroids for disease control. This is a serious mistake, emphasized Dr. Loftus, professor of medicine and director of the IBD Interest Group at the Mayo Clinic in Rochester, Minn.

“When you say, ‘Oh, I’ll just give that patient another prednisone taper, he doesn’t want to start taking a TNF inhibitor,’ you’re actually doing the patient harm. You’re actually affecting the patient’s life expectancy when you do that,” he declared. “The message is, yes, steroids are cheap, steroids are easy, nobody’s afraid of steroids, but you should be afraid of steroids.”

The 1,879 Crohn’s disease patients who entered the cohort as new users of anti-TNF therapy had a subsequent mortality incidence rate of 21.4 per 1,000 person-years, compared with a rate of 30.1 per 1,000 person-years in the 7,694 who entered the study period as prolonged steroid users. In a multivariate analysis accounting for 57 potential confounding factors, this translated to a highly significant 22% relative risk reduction in mortality in the patients who went with anti-TNF therapy (Am J Gastroenterol. 2018 Jan 16. doi: 10.1038/ajg.2017.479).

A similar trend was seen in the ulcerative colitis cohort. The 459 ulcerative colitis patients who entered the cohort as new anti-TNF therapy users had a mortality incidence rate of 23.0 per 1,000 person-years, compared with a rate of 30.9 in the 3,224 who received more than 3,000 mg of prednisone in the next 12 months. This represented a 14% relative risk reduction, although this favorable trend did not achieve statistical significance, perhaps because of the smaller size of the ulcerative colitis cohort.

In addition to demonstrably greater life expectancy, anti-TNF therapy offered additional benefits: a 32% reduction in the risk of major adverse cardiovascular events and a 46% lower incidence of hip fracture.

Dr. Sandborn, professor of medicine and chief of the division of gastroenterology at the University of California, San Diego, spun the study data another way: “It shows the number needed to kill is 33. So for every 33 patients you put on prolonged corticosteroids, you’re killing one extra patient by doing that. Of course, you probably blame it on their age and comorbidities, but this is it. This is the data.”

TNF blockers, thiopurines, and lymphoma

The use of thiopurines for treatment of IBD is widely recognized to be associated with a small but real increased risk of lymphoma. Now a large French national study has demonstrated for the first time that anti-TNF therapy for IBD is also associated with an increased risk that needs to be discussed with patients. And in IBD patients on combination therapy with both classes of medication, that risk jumps to 6.1-fold greater than in unexposed IBD patients (JAMA 2017 Nov 7;318[17]:1679-86).

Dr. Loftus and Dr. Sandborn urged their colleagues to keep this increased risk in perspective in counseling patients by focusing on the modest absolute increase in risk rather than the scarier-sounding relative risk. Notably, two-thirds of lymphomas in the French study occurred in patients not on thiopurines or anti-TNF agents.

“The most interesting thing to me is that we worry and worry about lymphoma, and guess what? In this study and in multiple other studies, the majority of lymphomas occurring in IBD patients have nothing to do with their medications. They’re due to the usual risk factors for lymphoma, which include age and male gender,” Dr. Loftus observed.

The French study included more than 189,000 IBD patients followed for a median of 6.7 years, during which 336 cases of lymphoma occurred. The incidence rate was 0.26 cases per 1,000 person-years in unexposed patients. The rate was significantly higher at 0.54 per 1,000 person-years in those on thiopurine monotherapy, increased to a similar extent at 0.41 cases per 1,000 person-years in patients on anti-TNF monotherapy, and 0.95 per 1,000 person-years in those on combination therapy.

In a multivariate analysis, the lymphoma risk was an adjusted 2.6-fold greater in patients exposed to thiopurine monotherapy than in unexposed patients, 2.41-fold greater in patients exposed to anti-TNF monotherapy, and 6.1-fold greater in those exposed to combination therapy.

“The point I want to make is the lymphoma rates in the thiopurine monotherapy and anti-TNF monotherapy groups are not significantly different. So the claim that’s been out there that the increased lymphoma risk in IBD patients can be completely explained by thiopurines is wrong. This study is showing us that with anti-TNF monotherapy there is still a low-level risk of lymphoma,” Dr. Loftus said.

“It is somewhat eyebrow-raising when you see that relative risk of 6.1, and that’s what patients are going to focus on, but when you counsel patients you have to redirect them to the absolute risk. You can say, ‘Even on combination therapy, your risk is 1 in 1,000,’ ” the gastroenterologist said.

Dr. Sandborn said the lymphoma signal hadn’t been spotted previously because the individual registries of IBD patients on anti-TNF agents are too small to allow for identification of a small increase in risk. The French investigators overcame that limitation by tapping into the country’s national health care system.

“This is a huge dataset and I think the message is unequivocal,” Dr. Sandborn said.

Preoperative vedolizumab and postoperative infection risk

“The overall safety profile of vedolizumab is pretty good,” Dr. Loftus observed. “The one unanswered question is its safety when used within 8-12 weeks of a major abdominal operation.”

It’s a clinically relevant question because vedolizumab selectively inhibits leukocyte migration into the intestinal tract, which could provide a mechanism for impaired postoperative wound healing in patients undergoing major abdominal surgery. And sooner or later a high proportion of IBD patients have a major abdominal operation.

Dr. Loftus and his coinvestigators kicked off a controversy by reporting a 37% incidence of surgical site infections in IBD patients who received vedolizumab within 30 days of a major abdominal operation in a retrospective chart review of the Mayo Clinic experience, a postoperative infection rate strikingly higher than in their patients on anti-TNF or nonbiologic therapy (J Crohns Colitis. 2017 Feb;11[2]:185-90).

This prompted investigators at the University of Chicago to look retrospectively at their institutional experience. They reported no increased risk in IBD patients on vedolizumab (Am J Gastroenterol. 2017 Sep;112[9]:1423-9). Neither did Belgian gastroenterologists at the Catholic University of Leuven (J Crohns Colitis. 2017 Oct 27;11[11]:1353-61).

Most recently, the Mayo Clinic group along with gastroenterologists at three other U.S. centers collaborated in a multicenter retrospective review of 146 adult IBD patients who received vedolizumab within 12 weeks before major abdominal surgery and 289 who received anti-TNF therapy. In a multivariate analysis, perioperative use of vedolizumab was independently associated with a 5.8-fold increased risk of developing a surgical site infection (J Inflamm Bowel Dis. 2018 Mar 19. doi: 10.1093/ibd/izx076).

Dr. Sandborn, who like Dr. Loftus was a coauthor of the multicenter study, drew back to look at the big picture.

“Is vedolizumab really causal? I doubt it, although it’s remotely possible. But I bet vedolizumab therapy is a really good marker for sick patients, and sick patients have worse operative outcomes, so we ought to be conservative with their surgery. My read of this is this [postoperative infection risk] isn’t unique to vedolizumab. Just be careful with sick patients when you’re operating and do more conservative surgeries,” he said.

Both gastroenterologists reported serving as consultants to and receiving research grants from numerous pharmaceutical companies.

bjancin@mdedge.com

SALT LAKE CITY – Hyperpolarized xenon-129 magnetic resonance imaging, or ¹²⁹Xe MRI, showed strong promise for revealing early lung ventilation deficits in pediatric hematopoietic stem cell transplant (HSCT) patients in a proof-of-concept study.

The use of hyperpolarized xenon gas in this setting remains investigational, but is emerging as a safe non-ionizing approach for mapping and quantifying regional airway obstruction in the pediatric population. It has been shown to be more sensitive to early disease than the current clinical gold standard of measuring forced expiratory volume in 1 second (FEV₁) by spirometry, Laura L. Walkup, PhD, said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The ¹²⁹Xe MRI provides regional information that spirometry cannot, allowing for a targeted approach to planned procedures such as bronchoscopy, said Dr. Walkup of Cincinnati Children’s Hospital Medical Center.

“We hypothesized that hyperpolarized ¹²⁹Xe MRI would be sensitive to lung abnormalities in the pediatric HSCT population,” she said.

Of 13 patients aged 6-13 years (mean, 10 years) who were enrolled in the study and underwent ¹²⁹XeMRI, 9 also completed spirometry successfully, and the average FEV₁ in those patients was 83% of the predicted value.

Ventilation deficits were apparent on the ¹²⁹Xe MRI imaging in 8 of the 13 subjects and varied in regional distribution. The whole-lung ¹²⁹Xe ventilation defect percentage for the HSCT group was 14%, which was significantly greater than the approximately 6% ventilation defect percentage in a cohort of age-matched controls, Dr. Walkup said, noting that ventilation deficits were seen in three of four subjects who were unable to complete reliable spirometry.

“So those are lung abnormalities that may have otherwise gone undetected,” she said, adding that hyperpolarized xenon gas also highlighted the wide individual variation in ventilation, even among cases with similar FEV₁ percentages.

The findings are notable, because pulmonary complications such as bronchiolitis obliterans are a major source of morbidity and mortality in the pediatric HSCT population, and an accurate and early diagnostic tool identifying the location and severity of suspected obstructive lung pathology following HSCT is desperately needed, she said.

The HSCT patients in the current study included four boys and nine girls. Isotopically-enriched xenon gas (86% ¹²⁹Xe) was hyperpolarized using a commercial polarizer and images were acquired during a breath hold of up to 16 seconds and up to 1 L of xenon gas. Conventional anatomic MR images also were acquired.

The ¹²⁹Xe ventilation was quantified using a less than 60% mean whole-lung ¹²⁹Xe signal threshold, and was compared to FEV₁ percentage predicted as measured via spirometry.

The procedure was well tolerated by all patients, Dr. Walkup said, noting that no patients withdrew from the study, and all were able to maintain the required breath hold.

Drops in blood oxygen saturation level did occur, but were transient and resolved within 10-30 seconds of normal breathing. Further, there were no changes in heart rate during imaging, and any side effects related to xenon, such as tingling in extremities, dizziness, or euphoria, were also quickly resolved with normal breathing, she said.

“There were no serious adverse events related to the study ... these results are in good agreement with previously published safety assessments of xenon in kids and in adults, and at our institution we routinely perform xenon imaging in children as young as age 6,” she added.

The findings, which are consistent with those seen in studies of other conditions such as cystic fibrosis, asthma, and chronic obstructive pulmonary disease, suggest that ¹²⁹Xe MRI is an emerging modality with strong translational potential for detecting early pulmonary involvement following HSCT, she said.

“The real power of the xenon MRI is the spatial information that it provides; we can use that information to plan targeted procedures like bronchoscopy and biopsies ... and since it is non-ionizing, it may be used serially to assess disease progression or response to an intervention,” Dr. Walkup said.

She noted, however, that because it is not yet approved by the Food and Drug Administration, and because it requires specialized expertise and hardware, it is available at only a handful of centers worldwide.

There is a long way to go before the technology will be widely clinically implemented, but work is ongoing at Cincinnati Children’s Hospital to determine how xenon MRI may play a role in pulmonary screening of patients, she said.

Dr. Walkup reported having no financial disclosures.

sworcester@mdedge.com

SOURCE: Walkup L et al. 2018 BMT Tandem Meetings Abstract 56.

SALT LAKE CITY – Hyperpolarized xenon-129 magnetic resonance imaging, or ¹²⁹Xe MRI, showed strong promise for revealing early lung ventilation deficits in pediatric hematopoietic stem cell transplant (HSCT) patients in a proof-of-concept study.

The use of hyperpolarized xenon gas in this setting remains investigational, but is emerging as a safe non-ionizing approach for mapping and quantifying regional airway obstruction in the pediatric population. It has been shown to be more sensitive to early disease than the current clinical gold standard of measuring forced expiratory volume in 1 second (FEV₁) by spirometry, Laura L. Walkup, PhD, said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The ¹²⁹Xe MRI provides regional information that spirometry cannot, allowing for a targeted approach to planned procedures such as bronchoscopy, said Dr. Walkup of Cincinnati Children’s Hospital Medical Center.

“We hypothesized that hyperpolarized ¹²⁹Xe MRI would be sensitive to lung abnormalities in the pediatric HSCT population,” she said.

Of 13 patients aged 6-13 years (mean, 10 years) who were enrolled in the study and underwent ¹²⁹XeMRI, 9 also completed spirometry successfully, and the average FEV₁ in those patients was 83% of the predicted value.

Ventilation deficits were apparent on the ¹²⁹Xe MRI imaging in 8 of the 13 subjects and varied in regional distribution. The whole-lung ¹²⁹Xe ventilation defect percentage for the HSCT group was 14%, which was significantly greater than the approximately 6% ventilation defect percentage in a cohort of age-matched controls, Dr. Walkup said, noting that ventilation deficits were seen in three of four subjects who were unable to complete reliable spirometry.

“So those are lung abnormalities that may have otherwise gone undetected,” she said, adding that hyperpolarized xenon gas also highlighted the wide individual variation in ventilation, even among cases with similar FEV₁ percentages.

The findings are notable, because pulmonary complications such as bronchiolitis obliterans are a major source of morbidity and mortality in the pediatric HSCT population, and an accurate and early diagnostic tool identifying the location and severity of suspected obstructive lung pathology following HSCT is desperately needed, she said.

The HSCT patients in the current study included four boys and nine girls. Isotopically-enriched xenon gas (86% ¹²⁹Xe) was hyperpolarized using a commercial polarizer and images were acquired during a breath hold of up to 16 seconds and up to 1 L of xenon gas. Conventional anatomic MR images also were acquired.

The ¹²⁹Xe ventilation was quantified using a less than 60% mean whole-lung ¹²⁹Xe signal threshold, and was compared to FEV₁ percentage predicted as measured via spirometry.

The procedure was well tolerated by all patients, Dr. Walkup said, noting that no patients withdrew from the study, and all were able to maintain the required breath hold.

Drops in blood oxygen saturation level did occur, but were transient and resolved within 10-30 seconds of normal breathing. Further, there were no changes in heart rate during imaging, and any side effects related to xenon, such as tingling in extremities, dizziness, or euphoria, were also quickly resolved with normal breathing, she said.

“There were no serious adverse events related to the study ... these results are in good agreement with previously published safety assessments of xenon in kids and in adults, and at our institution we routinely perform xenon imaging in children as young as age 6,” she added.

The findings, which are consistent with those seen in studies of other conditions such as cystic fibrosis, asthma, and chronic obstructive pulmonary disease, suggest that ¹²⁹Xe MRI is an emerging modality with strong translational potential for detecting early pulmonary involvement following HSCT, she said.

“The real power of the xenon MRI is the spatial information that it provides; we can use that information to plan targeted procedures like bronchoscopy and biopsies ... and since it is non-ionizing, it may be used serially to assess disease progression or response to an intervention,” Dr. Walkup said.

She noted, however, that because it is not yet approved by the Food and Drug Administration, and because it requires specialized expertise and hardware, it is available at only a handful of centers worldwide.

There is a long way to go before the technology will be widely clinically implemented, but work is ongoing at Cincinnati Children’s Hospital to determine how xenon MRI may play a role in pulmonary screening of patients, she said.

Dr. Walkup reported having no financial disclosures.

sworcester@mdedge.com

SOURCE: Walkup L et al. 2018 BMT Tandem Meetings Abstract 56.

SALT LAKE CITY – Hyperpolarized xenon-129 magnetic resonance imaging, or ¹²⁹Xe MRI, showed strong promise for revealing early lung ventilation deficits in pediatric hematopoietic stem cell transplant (HSCT) patients in a proof-of-concept study.

The use of hyperpolarized xenon gas in this setting remains investigational, but is emerging as a safe non-ionizing approach for mapping and quantifying regional airway obstruction in the pediatric population. It has been shown to be more sensitive to early disease than the current clinical gold standard of measuring forced expiratory volume in 1 second (FEV₁) by spirometry, Laura L. Walkup, PhD, said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The ¹²⁹Xe MRI provides regional information that spirometry cannot, allowing for a targeted approach to planned procedures such as bronchoscopy, said Dr. Walkup of Cincinnati Children’s Hospital Medical Center.

“We hypothesized that hyperpolarized ¹²⁹Xe MRI would be sensitive to lung abnormalities in the pediatric HSCT population,” she said.

Of 13 patients aged 6-13 years (mean, 10 years) who were enrolled in the study and underwent ¹²⁹XeMRI, 9 also completed spirometry successfully, and the average FEV₁ in those patients was 83% of the predicted value.

Ventilation deficits were apparent on the ¹²⁹Xe MRI imaging in 8 of the 13 subjects and varied in regional distribution. The whole-lung ¹²⁹Xe ventilation defect percentage for the HSCT group was 14%, which was significantly greater than the approximately 6% ventilation defect percentage in a cohort of age-matched controls, Dr. Walkup said, noting that ventilation deficits were seen in three of four subjects who were unable to complete reliable spirometry.

“So those are lung abnormalities that may have otherwise gone undetected,” she said, adding that hyperpolarized xenon gas also highlighted the wide individual variation in ventilation, even among cases with similar FEV₁ percentages.

The findings are notable, because pulmonary complications such as bronchiolitis obliterans are a major source of morbidity and mortality in the pediatric HSCT population, and an accurate and early diagnostic tool identifying the location and severity of suspected obstructive lung pathology following HSCT is desperately needed, she said.

The HSCT patients in the current study included four boys and nine girls. Isotopically-enriched xenon gas (86% ¹²⁹Xe) was hyperpolarized using a commercial polarizer and images were acquired during a breath hold of up to 16 seconds and up to 1 L of xenon gas. Conventional anatomic MR images also were acquired.

The ¹²⁹Xe ventilation was quantified using a less than 60% mean whole-lung ¹²⁹Xe signal threshold, and was compared to FEV₁ percentage predicted as measured via spirometry.

The procedure was well tolerated by all patients, Dr. Walkup said, noting that no patients withdrew from the study, and all were able to maintain the required breath hold.

Drops in blood oxygen saturation level did occur, but were transient and resolved within 10-30 seconds of normal breathing. Further, there were no changes in heart rate during imaging, and any side effects related to xenon, such as tingling in extremities, dizziness, or euphoria, were also quickly resolved with normal breathing, she said.

“There were no serious adverse events related to the study ... these results are in good agreement with previously published safety assessments of xenon in kids and in adults, and at our institution we routinely perform xenon imaging in children as young as age 6,” she added.

The findings, which are consistent with those seen in studies of other conditions such as cystic fibrosis, asthma, and chronic obstructive pulmonary disease, suggest that ¹²⁹Xe MRI is an emerging modality with strong translational potential for detecting early pulmonary involvement following HSCT, she said.

“The real power of the xenon MRI is the spatial information that it provides; we can use that information to plan targeted procedures like bronchoscopy and biopsies ... and since it is non-ionizing, it may be used serially to assess disease progression or response to an intervention,” Dr. Walkup said.

She noted, however, that because it is not yet approved by the Food and Drug Administration, and because it requires specialized expertise and hardware, it is available at only a handful of centers worldwide.

There is a long way to go before the technology will be widely clinically implemented, but work is ongoing at Cincinnati Children’s Hospital to determine how xenon MRI may play a role in pulmonary screening of patients, she said.

Dr. Walkup reported having no financial disclosures.

sworcester@mdedge.com

SOURCE: Walkup L et al. 2018 BMT Tandem Meetings Abstract 56.

What’s not to love about podcasts? Advice, comedy, news, and drama delivered directly to your brain. Unlike blogs or articles, you need no effort to enjoy them. Indeed, you can be actively engaged elsewhere: running, cycling, commuting, or simply loafing. The detail and richness of the sound also creates an intimate connection with the host in a way other mediums cannot. It feels like they are talking only to you.

Yet, there is a problem with podcasts: There are too many of them. If I listened continuously to the episodes in my queue it would take 6 months. I suppose I could see patients and listen at the same time. (Yes, I have a problem.) I also own far more books than I’ll ever read. Aspirational, I call it.

Martinan/Thinkstock

If, like me, you’re unable to dedicate your life to consuming podcasts, you might appreciate a few recommendations. Here’s a charcuterie board of tasty bits, carefully curated to avoid political allergies and Dunning-Kruger references.

 

1. Physicians Practice. It’s one of the oldest podcasts running and addresses a wide range of issues affecting health care professionals and the industry at large. Episodes are short (typically under 10 minutes) and address a range of issues relevant to both young and seasoned physicians With scores of podcasts from which to choose, I suggest just selecting one and jumping in. With episode titles such as “The Patient Empathy Problem Physicians Must Face” and “EHRs Not Designed with Real People in Mind, Expert Opines,” it’s easy to do.

2. UpToDate. If you’re looking for straight clinical talk buttressed with scientific evidence, then download UpToDate. Episodes typically feature interviews with one or two respected physician leaders who share their clinical findings. You can select episode topics based upon clinical specialty or simply start listening. Here is a sampling of topics: sentinel lymph node metastasis in melanoma; dexamethasone and acute pharyngitis pain in adults; management of anticoagulation for patients with nonvalvular atrial fibrillation. UpToDate states that it is entirely funded by user subscriptions and does not accept advertising or funding unrelated to subscriptions.

3. Bedside Rounds. The tagline for the podcast Bedside Rounds is “Because medicine is awesome.” This is not meant to be ironic. Creator and host, Adam Rodman, MD, a global health hospitalist who divides his time between Boston (at the Beth Israel Deaconess Medical Center) and Botswana, is that eager kid in the classroom who sits in the front row just because he’s so excited to be there. Unlike UpToDate, which focuses on current advances in clinical medicine, Bedside Rounds explores both the science and art of medicine through captivating stories heavily rooted in the history of medicine. Instead of brushing the dust off of your old medical books, tune in to Bedside Rounds to hear stories such as “Bone Portraits,” which explores the history of radiation, and “Curse of the Ninth,” which explores whether or not composer Gustav Mahler, worked his heart murmur into his famous Ninth Symphony.

4. The Adventures of Memento Mori. Creator and host, D.S. Moss, has created a podcast about death, or, to be more upbeat, the quest for the meaning of life. A screenwriter/producer, Mr. Moss deep dives into all things death. But it’s not as depressing as it sounds. “Memento mori,” he explains, is Latin for being mindful that you will die. As a result, Mr. Moss has created his podcast with the goal of encouraging listeners to live a more engaged, mindful, and meaningful life. We can apply many of these lessons to our own professional and personal lives and perhaps learn some ways to help our patients cope with terminal illness and mortality. Topics range from the emotional (“Thoughts in Passing,” which features several hospice patients) to the technological (“Digital Afterlife,” which explores what our digital legacies say about us), to the scientific (“The Science of Immortality,” which explores venture capital’s movement in the science of living forever).

5. Invisibilia. Invisibilia – Latin for invisible things – is an exploration of the “unseeable forces” that shape human behavior – our beliefs, thoughts, and assumptions. Hosts Alix Spiegel and Hanna Rosin, both of National Public Radio, seamlessly weave storytelling, interviewing, and scientific data to tackle a wide range of topics such as prejudice and implicit bias in “The Culture Inside” to people’s desire for radical change in “Bubble Hopping.” Part behavioral economics, part neuroscience, part sociology, part pop culture, fully fascinating.

6. Jocko Podcast. Jocko Willink, a retired Navy SEAL and motivational author and speaker, along with Echo Charles, conduct compelling interviews with leaders from various fields including the military, sports, medicine, and the arts. Mr. Willink’s style of motivation is refreshingly honest and direct. I have taken tips from his podcasts that have helped me become a more efficient and energetic physician and leader. Two fundamental themes that run through his podcast are the value of treating people well and of living your life with discipline. It gets you a long way as a Navy SEAL, as well as a doctor. One of my personal favorites is Episode 69: “The Real Top Gun. Battlefield, Work, and Life are Identical” with Elite Marine Fighter Pilot, David Berke. If that doesn’t pique your interest, no worries; there are over 100 episodes from which to choose.

There are many, many more podcasts I’d like to recommend, but I’ll show some discipline (thanks, Jocko) and save them for next time.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@frontlinemedcom.com.

What’s not to love about podcasts? Advice, comedy, news, and drama delivered directly to your brain. Unlike blogs or articles, you need no effort to enjoy them. Indeed, you can be actively engaged elsewhere: running, cycling, commuting, or simply loafing. The detail and richness of the sound also creates an intimate connection with the host in a way other mediums cannot. It feels like they are talking only to you.

Yet, there is a problem with podcasts: There are too many of them. If I listened continuously to the episodes in my queue it would take 6 months. I suppose I could see patients and listen at the same time. (Yes, I have a problem.) I also own far more books than I’ll ever read. Aspirational, I call it.

Martinan/Thinkstock

If, like me, you’re unable to dedicate your life to consuming podcasts, you might appreciate a few recommendations. Here’s a charcuterie board of tasty bits, carefully curated to avoid political allergies and Dunning-Kruger references.

 

1. Physicians Practice. It’s one of the oldest podcasts running and addresses a wide range of issues affecting health care professionals and the industry at large. Episodes are short (typically under 10 minutes) and address a range of issues relevant to both young and seasoned physicians With scores of podcasts from which to choose, I suggest just selecting one and jumping in. With episode titles such as “The Patient Empathy Problem Physicians Must Face” and “EHRs Not Designed with Real People in Mind, Expert Opines,” it’s easy to do.

2. UpToDate. If you’re looking for straight clinical talk buttressed with scientific evidence, then download UpToDate. Episodes typically feature interviews with one or two respected physician leaders who share their clinical findings. You can select episode topics based upon clinical specialty or simply start listening. Here is a sampling of topics: sentinel lymph node metastasis in melanoma; dexamethasone and acute pharyngitis pain in adults; management of anticoagulation for patients with nonvalvular atrial fibrillation. UpToDate states that it is entirely funded by user subscriptions and does not accept advertising or funding unrelated to subscriptions.

3. Bedside Rounds. The tagline for the podcast Bedside Rounds is “Because medicine is awesome.” This is not meant to be ironic. Creator and host, Adam Rodman, MD, a global health hospitalist who divides his time between Boston (at the Beth Israel Deaconess Medical Center) and Botswana, is that eager kid in the classroom who sits in the front row just because he’s so excited to be there. Unlike UpToDate, which focuses on current advances in clinical medicine, Bedside Rounds explores both the science and art of medicine through captivating stories heavily rooted in the history of medicine. Instead of brushing the dust off of your old medical books, tune in to Bedside Rounds to hear stories such as “Bone Portraits,” which explores the history of radiation, and “Curse of the Ninth,” which explores whether or not composer Gustav Mahler, worked his heart murmur into his famous Ninth Symphony.

4. The Adventures of Memento Mori. Creator and host, D.S. Moss, has created a podcast about death, or, to be more upbeat, the quest for the meaning of life. A screenwriter/producer, Mr. Moss deep dives into all things death. But it’s not as depressing as it sounds. “Memento mori,” he explains, is Latin for being mindful that you will die. As a result, Mr. Moss has created his podcast with the goal of encouraging listeners to live a more engaged, mindful, and meaningful life. We can apply many of these lessons to our own professional and personal lives and perhaps learn some ways to help our patients cope with terminal illness and mortality. Topics range from the emotional (“Thoughts in Passing,” which features several hospice patients) to the technological (“Digital Afterlife,” which explores what our digital legacies say about us), to the scientific (“The Science of Immortality,” which explores venture capital’s movement in the science of living forever).

5. Invisibilia. Invisibilia – Latin for invisible things – is an exploration of the “unseeable forces” that shape human behavior – our beliefs, thoughts, and assumptions. Hosts Alix Spiegel and Hanna Rosin, both of National Public Radio, seamlessly weave storytelling, interviewing, and scientific data to tackle a wide range of topics such as prejudice and implicit bias in “The Culture Inside” to people’s desire for radical change in “Bubble Hopping.” Part behavioral economics, part neuroscience, part sociology, part pop culture, fully fascinating.

6. Jocko Podcast. Jocko Willink, a retired Navy SEAL and motivational author and speaker, along with Echo Charles, conduct compelling interviews with leaders from various fields including the military, sports, medicine, and the arts. Mr. Willink’s style of motivation is refreshingly honest and direct. I have taken tips from his podcasts that have helped me become a more efficient and energetic physician and leader. Two fundamental themes that run through his podcast are the value of treating people well and of living your life with discipline. It gets you a long way as a Navy SEAL, as well as a doctor. One of my personal favorites is Episode 69: “The Real Top Gun. Battlefield, Work, and Life are Identical” with Elite Marine Fighter Pilot, David Berke. If that doesn’t pique your interest, no worries; there are over 100 episodes from which to choose.

There are many, many more podcasts I’d like to recommend, but I’ll show some discipline (thanks, Jocko) and save them for next time.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@frontlinemedcom.com.

What’s not to love about podcasts? Advice, comedy, news, and drama delivered directly to your brain. Unlike blogs or articles, you need no effort to enjoy them. Indeed, you can be actively engaged elsewhere: running, cycling, commuting, or simply loafing. The detail and richness of the sound also creates an intimate connection with the host in a way other mediums cannot. It feels like they are talking only to you.

Yet, there is a problem with podcasts: There are too many of them. If I listened continuously to the episodes in my queue it would take 6 months. I suppose I could see patients and listen at the same time. (Yes, I have a problem.) I also own far more books than I’ll ever read. Aspirational, I call it.

Martinan/Thinkstock

If, like me, you’re unable to dedicate your life to consuming podcasts, you might appreciate a few recommendations. Here’s a charcuterie board of tasty bits, carefully curated to avoid political allergies and Dunning-Kruger references.

 

1. Physicians Practice. It’s one of the oldest podcasts running and addresses a wide range of issues affecting health care professionals and the industry at large. Episodes are short (typically under 10 minutes) and address a range of issues relevant to both young and seasoned physicians With scores of podcasts from which to choose, I suggest just selecting one and jumping in. With episode titles such as “The Patient Empathy Problem Physicians Must Face” and “EHRs Not Designed with Real People in Mind, Expert Opines,” it’s easy to do.

2. UpToDate. If you’re looking for straight clinical talk buttressed with scientific evidence, then download UpToDate. Episodes typically feature interviews with one or two respected physician leaders who share their clinical findings. You can select episode topics based upon clinical specialty or simply start listening. Here is a sampling of topics: sentinel lymph node metastasis in melanoma; dexamethasone and acute pharyngitis pain in adults; management of anticoagulation for patients with nonvalvular atrial fibrillation. UpToDate states that it is entirely funded by user subscriptions and does not accept advertising or funding unrelated to subscriptions.

3. Bedside Rounds. The tagline for the podcast Bedside Rounds is “Because medicine is awesome.” This is not meant to be ironic. Creator and host, Adam Rodman, MD, a global health hospitalist who divides his time between Boston (at the Beth Israel Deaconess Medical Center) and Botswana, is that eager kid in the classroom who sits in the front row just because he’s so excited to be there. Unlike UpToDate, which focuses on current advances in clinical medicine, Bedside Rounds explores both the science and art of medicine through captivating stories heavily rooted in the history of medicine. Instead of brushing the dust off of your old medical books, tune in to Bedside Rounds to hear stories such as “Bone Portraits,” which explores the history of radiation, and “Curse of the Ninth,” which explores whether or not composer Gustav Mahler, worked his heart murmur into his famous Ninth Symphony.

4. The Adventures of Memento Mori. Creator and host, D.S. Moss, has created a podcast about death, or, to be more upbeat, the quest for the meaning of life. A screenwriter/producer, Mr. Moss deep dives into all things death. But it’s not as depressing as it sounds. “Memento mori,” he explains, is Latin for being mindful that you will die. As a result, Mr. Moss has created his podcast with the goal of encouraging listeners to live a more engaged, mindful, and meaningful life. We can apply many of these lessons to our own professional and personal lives and perhaps learn some ways to help our patients cope with terminal illness and mortality. Topics range from the emotional (“Thoughts in Passing,” which features several hospice patients) to the technological (“Digital Afterlife,” which explores what our digital legacies say about us), to the scientific (“The Science of Immortality,” which explores venture capital’s movement in the science of living forever).

5. Invisibilia. Invisibilia – Latin for invisible things – is an exploration of the “unseeable forces” that shape human behavior – our beliefs, thoughts, and assumptions. Hosts Alix Spiegel and Hanna Rosin, both of National Public Radio, seamlessly weave storytelling, interviewing, and scientific data to tackle a wide range of topics such as prejudice and implicit bias in “The Culture Inside” to people’s desire for radical change in “Bubble Hopping.” Part behavioral economics, part neuroscience, part sociology, part pop culture, fully fascinating.

6. Jocko Podcast. Jocko Willink, a retired Navy SEAL and motivational author and speaker, along with Echo Charles, conduct compelling interviews with leaders from various fields including the military, sports, medicine, and the arts. Mr. Willink’s style of motivation is refreshingly honest and direct. I have taken tips from his podcasts that have helped me become a more efficient and energetic physician and leader. Two fundamental themes that run through his podcast are the value of treating people well and of living your life with discipline. It gets you a long way as a Navy SEAL, as well as a doctor. One of my personal favorites is Episode 69: “The Real Top Gun. Battlefield, Work, and Life are Identical” with Elite Marine Fighter Pilot, David Berke. If that doesn’t pique your interest, no worries; there are over 100 episodes from which to choose.

There are many, many more podcasts I’d like to recommend, but I’ll show some discipline (thanks, Jocko) and save them for next time.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@frontlinemedcom.com.

How to avoid warfarin’s polypharmacy dangers. Which non-AIDS conditions hint at HIV infection? How San Francisco delivers faster HIV treatment. And red meat may fuel the rise of fatty livers.

Listen to the MDedge Daily News podcast for all the details on today’s top news.

How to avoid warfarin’s polypharmacy dangers. Which non-AIDS conditions hint at HIV infection? How San Francisco delivers faster HIV treatment. And red meat may fuel the rise of fatty livers.

Listen to the MDedge Daily News podcast for all the details on today’s top news.

How to avoid warfarin’s polypharmacy dangers. Which non-AIDS conditions hint at HIV infection? How San Francisco delivers faster HIV treatment. And red meat may fuel the rise of fatty livers.

Listen to the MDedge Daily News podcast for all the details on today’s top news.

An “unparalleled dataset” is providing high-quality information on the many factors that influence brain, cognitive, social, and emotional development in children.

The Adolescent Brain Cognitive Development (ABCD) study, involving > 7,500  children aged between  9 and 10 years and their families, is the largest long-term study of brain development and child health in the US. Interim results on about 30 terabytes of data (3 times the size of the Library of Congress collection) obtained from the first 4,500 participants will allow scientists to begin analyzing and publishing novel research, according to Nora Volkow, MD, director of the National Institute on Drug Abuse.

Researchers will be able to examine many aspects of growth and development, such as the impact of sports injuries on developmental outcomes, the relationship between screen time and brain and social development, and which brain pathways are associated with the onset and progression of mental health disorders.

The study aims to enroll 11,500 children by the end of 2018. Participants will be followed for 10 years, with data collected every 6 months through interviews and behavioral testing. Neuroimaging data, including high resolution MRI, are collected every 2 years.

An “unparalleled dataset” is providing high-quality information on the many factors that influence brain, cognitive, social, and emotional development in children.

The Adolescent Brain Cognitive Development (ABCD) study, involving > 7,500  children aged between  9 and 10 years and their families, is the largest long-term study of brain development and child health in the US. Interim results on about 30 terabytes of data (3 times the size of the Library of Congress collection) obtained from the first 4,500 participants will allow scientists to begin analyzing and publishing novel research, according to Nora Volkow, MD, director of the National Institute on Drug Abuse.

Researchers will be able to examine many aspects of growth and development, such as the impact of sports injuries on developmental outcomes, the relationship between screen time and brain and social development, and which brain pathways are associated with the onset and progression of mental health disorders.

The study aims to enroll 11,500 children by the end of 2018. Participants will be followed for 10 years, with data collected every 6 months through interviews and behavioral testing. Neuroimaging data, including high resolution MRI, are collected every 2 years.

An “unparalleled dataset” is providing high-quality information on the many factors that influence brain, cognitive, social, and emotional development in children.

The Adolescent Brain Cognitive Development (ABCD) study, involving > 7,500  children aged between  9 and 10 years and their families, is the largest long-term study of brain development and child health in the US. Interim results on about 30 terabytes of data (3 times the size of the Library of Congress collection) obtained from the first 4,500 participants will allow scientists to begin analyzing and publishing novel research, according to Nora Volkow, MD, director of the National Institute on Drug Abuse.

Researchers will be able to examine many aspects of growth and development, such as the impact of sports injuries on developmental outcomes, the relationship between screen time and brain and social development, and which brain pathways are associated with the onset and progression of mental health disorders.

The study aims to enroll 11,500 children by the end of 2018. Participants will be followed for 10 years, with data collected every 6 months through interviews and behavioral testing. Neuroimaging data, including high resolution MRI, are collected every 2 years.

Photo by Chad McNeeley

LISBON—Results of a large study revealed a higher incidence of adenovirus (AdV) infection after allogeneic hematopoietic stem cell transplant (allo-HSCT) in children than adults.

The rate of AdV infection in the 6 months after allo-HSCT was 32% in children and 6% in adults.

However, researchers believe this data may be influenced by a lack of routine AdV screening in adults.

These findings—from the AdVance study—were reported at the 44th Annual Meeting of the EBMT as abstracts OS9-7 and B043.*

Other results from AdVance were also presented at the meeting, with mortality data reported as abstract OS9-8 and hospitalization data reported as abstract B073. The AdVance study was sponsored by Chimerix, Inc.

“The robust findings of the AdVance study are extremely important for transplant clinicians, as we seek to better understand the rates and clinical outcomes of adenovirus infection and assess ways to evaluate antiviral therapies,” said study investigator Marco Zecca, MD, of Fondazione IRCCS Policlinico San Matteo in Pavia, Italy.

AdVance is a multi-center, retrospective study of 4276 allo-HSCT recipients—1738 pediatric patients and 2538 adults. The patients underwent transplants at 50 centers in Europe from January 2013 to September 2015.

Abstract OS9-7: Incidence

Thirty-two percent (n=558) of pediatric patients developed an AdV infection in the first 6 months after allo-HSCT, and 23% (n=395) developed detectable AdV viremia. Fourteen percent (n=241) had AdV viremia ≥ 1000 copies/mL, a level previously associated with negative clinical outcomes.

Meanwhile, 6% (n=141) of adults had an AdV infection in the 6 months after transplant, 3% (n=77) developed AdV viremia, and 2% (n=39) had ≥ 1000 copies /mL.

Further analysis revealed that age, donor type, and use of T-cell depletion were independent predictors of AdV viremia ≥ 1000 copies/mL.

Older age was associated with a lower risk of AdV viremia ≥ 1000 copies/mL. There was a stepwise reduction in risk with increasing age (compared to ages 0-2, P=0.104 for ages 2-12, P=0.001 for ages 13-17, and P<0.0001 for ages 18-65+).

T-cell depletion was associated with an increased risk of AdV viremia ≥ 1000 copies/mL. Compared to no T-cell depletion, there was an increased risk for depletion with antithymocyte globulin (P=0.036) or alemtuzumab (P<0.0001) and for ex vivo depletion (P=0.002).

Compared to patients who received a matched related transplant, recipients of other transplants had an increased risk of AdV viremia ≥ 1000 copies/mL. This includes matched unrelated (P=0.016), cord blood (P=0.011), haploidentical (P=0.007), and mismatched (P<0.001) transplants.

Abstract B043: Screening

Dr Zecca and his colleagues believe the difference in AdV incidence between children and adults may have been affected by a lack of routine screening in adults.

To assess the use of screening, the investigators analyzed practice surveys from physicians at centers included in the AdVance study. There were 28 survey respondents who treat pediatric patients and 14 who treat adults.

All 28 physicians treating pediatric patients said there is routine AdV screening at their center. Ninety-three percent of these doctors said they routinely screen all pediatric allo-HSCT recipients for AdV infection. The remaining 7% said they screen patients considered to be at high-risk of AdV infection.

Thirty-six percent of the physicians treating adults (5/14) said they routinely screen for AdV, and 21% (3/14) said they routinely screen all of their adult allo-HSCT recipients for AdV infection.

Of the 11 doctors who said they did not routinely screen adult allo-HSCT recipients, some said they would screen recipients with a high-risk of AdV infection, such as those with graft-versus-host disease (4/11) or those who received haploidentical, mismatched, or cord blood transplants (3/11).

*Data in the abstracts differ from the presentations.

Photo by Chad McNeeley

LISBON—Results of a large study revealed a higher incidence of adenovirus (AdV) infection after allogeneic hematopoietic stem cell transplant (allo-HSCT) in children than adults.

The rate of AdV infection in the 6 months after allo-HSCT was 32% in children and 6% in adults.

However, researchers believe this data may be influenced by a lack of routine AdV screening in adults.

These findings—from the AdVance study—were reported at the 44th Annual Meeting of the EBMT as abstracts OS9-7 and B043.*

Other results from AdVance were also presented at the meeting, with mortality data reported as abstract OS9-8 and hospitalization data reported as abstract B073. The AdVance study was sponsored by Chimerix, Inc.

“The robust findings of the AdVance study are extremely important for transplant clinicians, as we seek to better understand the rates and clinical outcomes of adenovirus infection and assess ways to evaluate antiviral therapies,” said study investigator Marco Zecca, MD, of Fondazione IRCCS Policlinico San Matteo in Pavia, Italy.

AdVance is a multi-center, retrospective study of 4276 allo-HSCT recipients—1738 pediatric patients and 2538 adults. The patients underwent transplants at 50 centers in Europe from January 2013 to September 2015.

Abstract OS9-7: Incidence

Thirty-two percent (n=558) of pediatric patients developed an AdV infection in the first 6 months after allo-HSCT, and 23% (n=395) developed detectable AdV viremia. Fourteen percent (n=241) had AdV viremia ≥ 1000 copies/mL, a level previously associated with negative clinical outcomes.

Meanwhile, 6% (n=141) of adults had an AdV infection in the 6 months after transplant, 3% (n=77) developed AdV viremia, and 2% (n=39) had ≥ 1000 copies /mL.

Further analysis revealed that age, donor type, and use of T-cell depletion were independent predictors of AdV viremia ≥ 1000 copies/mL.

Older age was associated with a lower risk of AdV viremia ≥ 1000 copies/mL. There was a stepwise reduction in risk with increasing age (compared to ages 0-2, P=0.104 for ages 2-12, P=0.001 for ages 13-17, and P<0.0001 for ages 18-65+).

T-cell depletion was associated with an increased risk of AdV viremia ≥ 1000 copies/mL. Compared to no T-cell depletion, there was an increased risk for depletion with antithymocyte globulin (P=0.036) or alemtuzumab (P<0.0001) and for ex vivo depletion (P=0.002).

Compared to patients who received a matched related transplant, recipients of other transplants had an increased risk of AdV viremia ≥ 1000 copies/mL. This includes matched unrelated (P=0.016), cord blood (P=0.011), haploidentical (P=0.007), and mismatched (P<0.001) transplants.

Abstract B043: Screening

Dr Zecca and his colleagues believe the difference in AdV incidence between children and adults may have been affected by a lack of routine screening in adults.

To assess the use of screening, the investigators analyzed practice surveys from physicians at centers included in the AdVance study. There were 28 survey respondents who treat pediatric patients and 14 who treat adults.

All 28 physicians treating pediatric patients said there is routine AdV screening at their center. Ninety-three percent of these doctors said they routinely screen all pediatric allo-HSCT recipients for AdV infection. The remaining 7% said they screen patients considered to be at high-risk of AdV infection.

Thirty-six percent of the physicians treating adults (5/14) said they routinely screen for AdV, and 21% (3/14) said they routinely screen all of their adult allo-HSCT recipients for AdV infection.

Of the 11 doctors who said they did not routinely screen adult allo-HSCT recipients, some said they would screen recipients with a high-risk of AdV infection, such as those with graft-versus-host disease (4/11) or those who received haploidentical, mismatched, or cord blood transplants (3/11).

*Data in the abstracts differ from the presentations.

Photo by Chad McNeeley

LISBON—Results of a large study revealed a higher incidence of adenovirus (AdV) infection after allogeneic hematopoietic stem cell transplant (allo-HSCT) in children than adults.

The rate of AdV infection in the 6 months after allo-HSCT was 32% in children and 6% in adults.

However, researchers believe this data may be influenced by a lack of routine AdV screening in adults.

These findings—from the AdVance study—were reported at the 44th Annual Meeting of the EBMT as abstracts OS9-7 and B043.*

Other results from AdVance were also presented at the meeting, with mortality data reported as abstract OS9-8 and hospitalization data reported as abstract B073. The AdVance study was sponsored by Chimerix, Inc.

“The robust findings of the AdVance study are extremely important for transplant clinicians, as we seek to better understand the rates and clinical outcomes of adenovirus infection and assess ways to evaluate antiviral therapies,” said study investigator Marco Zecca, MD, of Fondazione IRCCS Policlinico San Matteo in Pavia, Italy.

AdVance is a multi-center, retrospective study of 4276 allo-HSCT recipients—1738 pediatric patients and 2538 adults. The patients underwent transplants at 50 centers in Europe from January 2013 to September 2015.

Abstract OS9-7: Incidence

Thirty-two percent (n=558) of pediatric patients developed an AdV infection in the first 6 months after allo-HSCT, and 23% (n=395) developed detectable AdV viremia. Fourteen percent (n=241) had AdV viremia ≥ 1000 copies/mL, a level previously associated with negative clinical outcomes.

Meanwhile, 6% (n=141) of adults had an AdV infection in the 6 months after transplant, 3% (n=77) developed AdV viremia, and 2% (n=39) had ≥ 1000 copies /mL.

Further analysis revealed that age, donor type, and use of T-cell depletion were independent predictors of AdV viremia ≥ 1000 copies/mL.

Older age was associated with a lower risk of AdV viremia ≥ 1000 copies/mL. There was a stepwise reduction in risk with increasing age (compared to ages 0-2, P=0.104 for ages 2-12, P=0.001 for ages 13-17, and P<0.0001 for ages 18-65+).

T-cell depletion was associated with an increased risk of AdV viremia ≥ 1000 copies/mL. Compared to no T-cell depletion, there was an increased risk for depletion with antithymocyte globulin (P=0.036) or alemtuzumab (P<0.0001) and for ex vivo depletion (P=0.002).

Compared to patients who received a matched related transplant, recipients of other transplants had an increased risk of AdV viremia ≥ 1000 copies/mL. This includes matched unrelated (P=0.016), cord blood (P=0.011), haploidentical (P=0.007), and mismatched (P<0.001) transplants.

Abstract B043: Screening

Dr Zecca and his colleagues believe the difference in AdV incidence between children and adults may have been affected by a lack of routine screening in adults.

To assess the use of screening, the investigators analyzed practice surveys from physicians at centers included in the AdVance study. There were 28 survey respondents who treat pediatric patients and 14 who treat adults.

All 28 physicians treating pediatric patients said there is routine AdV screening at their center. Ninety-three percent of these doctors said they routinely screen all pediatric allo-HSCT recipients for AdV infection. The remaining 7% said they screen patients considered to be at high-risk of AdV infection.

Thirty-six percent of the physicians treating adults (5/14) said they routinely screen for AdV, and 21% (3/14) said they routinely screen all of their adult allo-HSCT recipients for AdV infection.

Of the 11 doctors who said they did not routinely screen adult allo-HSCT recipients, some said they would screen recipients with a high-risk of AdV infection, such as those with graft-versus-host disease (4/11) or those who received haploidentical, mismatched, or cord blood transplants (3/11).

*Data in the abstracts differ from the presentations.

G. William Gary Jr.

LISBON—Data from the AdVance study revealed a “strong correlation” between adenovirus (AdV) viral load and mortality in pediatric recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT), according to researchers.

The team found that patients with the highest AdV viral burden had roughly 12 times the risk of all-cause mortality as patients with the lowest viral burden.

These findings were presented at the 44th Annual Meeting of the EBMT (abstract OS9-8).*

Other findings from AdVance were also reported at the meeting (abstracts OS9-7 and B043 as well as B073). The study was sponsored by Chimerix, Inc.

AdVance is a multi-center, retrospective study of 4276 allo-HSCT recipients, including 1738 pediatric patients. The patients underwent transplants at 50 centers in Europe from January 2013 to September 2015.

Thirty-two percent (n=558) of pediatric patients developed an AdV infection in the first 6 months after allo-HSCT. Twenty-three percent (n=395) developed detectable AdV viremia, and 14% (n=241) had AdV viremia ≥ 1000 copies/mL.

The researchers assessed AdV plasma viral burden, measured by time-averaged area under the curve (AAUC) over 16 weeks from the time of viremia ≥ 1000 copies/mL, and its correlation with all-cause mortality.

“[T]he highest mortality was observed in those with the greatest adenovirus burden,” said AdVance investigator Marco Zecca, MD, of Fondazione IRCCS Policlinico San Matteo in Pavia, Italy.

He and his colleagues divided patients into 4 quartiles according to AdV AAUC, with the third and fourth quartiles reflecting higher, more prolonged AdV viremia.

Rates of all-cause mortality at 6 months (from the first viremia ≥ 1000 copies/mL) were 52% in the fourth quartile, 10% in the third, 7% in the second, and 3% in the first quartile.

Forty percent of patients in the fourth quartile died within 2 months of transplant.

The hazard ratio for mortality was 11.7 in the fourth quartile, 2.7 in the third, and 1.5 in the second, with the first quartile as the reference.

“These data suggest that AdV AAUC is an appropriate endpoint to assess the potential benefits of antiviral therapies for the treatment of adenovirus,” Dr Zecca concluded.

*Data in the abstract differ from the presentation.

G. William Gary Jr.

LISBON—Data from the AdVance study revealed a “strong correlation” between adenovirus (AdV) viral load and mortality in pediatric recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT), according to researchers.

The team found that patients with the highest AdV viral burden had roughly 12 times the risk of all-cause mortality as patients with the lowest viral burden.

These findings were presented at the 44th Annual Meeting of the EBMT (abstract OS9-8).*

Other findings from AdVance were also reported at the meeting (abstracts OS9-7 and B043 as well as B073). The study was sponsored by Chimerix, Inc.

AdVance is a multi-center, retrospective study of 4276 allo-HSCT recipients, including 1738 pediatric patients. The patients underwent transplants at 50 centers in Europe from January 2013 to September 2015.

Thirty-two percent (n=558) of pediatric patients developed an AdV infection in the first 6 months after allo-HSCT. Twenty-three percent (n=395) developed detectable AdV viremia, and 14% (n=241) had AdV viremia ≥ 1000 copies/mL.

The researchers assessed AdV plasma viral burden, measured by time-averaged area under the curve (AAUC) over 16 weeks from the time of viremia ≥ 1000 copies/mL, and its correlation with all-cause mortality.

“[T]he highest mortality was observed in those with the greatest adenovirus burden,” said AdVance investigator Marco Zecca, MD, of Fondazione IRCCS Policlinico San Matteo in Pavia, Italy.

He and his colleagues divided patients into 4 quartiles according to AdV AAUC, with the third and fourth quartiles reflecting higher, more prolonged AdV viremia.

Rates of all-cause mortality at 6 months (from the first viremia ≥ 1000 copies/mL) were 52% in the fourth quartile, 10% in the third, 7% in the second, and 3% in the first quartile.

Forty percent of patients in the fourth quartile died within 2 months of transplant.

The hazard ratio for mortality was 11.7 in the fourth quartile, 2.7 in the third, and 1.5 in the second, with the first quartile as the reference.

“These data suggest that AdV AAUC is an appropriate endpoint to assess the potential benefits of antiviral therapies for the treatment of adenovirus,” Dr Zecca concluded.

*Data in the abstract differ from the presentation.

G. William Gary Jr.

LISBON—Data from the AdVance study revealed a “strong correlation” between adenovirus (AdV) viral load and mortality in pediatric recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT), according to researchers.

The team found that patients with the highest AdV viral burden had roughly 12 times the risk of all-cause mortality as patients with the lowest viral burden.

These findings were presented at the 44th Annual Meeting of the EBMT (abstract OS9-8).*

Other findings from AdVance were also reported at the meeting (abstracts OS9-7 and B043 as well as B073). The study was sponsored by Chimerix, Inc.

AdVance is a multi-center, retrospective study of 4276 allo-HSCT recipients, including 1738 pediatric patients. The patients underwent transplants at 50 centers in Europe from January 2013 to September 2015.

Thirty-two percent (n=558) of pediatric patients developed an AdV infection in the first 6 months after allo-HSCT. Twenty-three percent (n=395) developed detectable AdV viremia, and 14% (n=241) had AdV viremia ≥ 1000 copies/mL.

The researchers assessed AdV plasma viral burden, measured by time-averaged area under the curve (AAUC) over 16 weeks from the time of viremia ≥ 1000 copies/mL, and its correlation with all-cause mortality.

“[T]he highest mortality was observed in those with the greatest adenovirus burden,” said AdVance investigator Marco Zecca, MD, of Fondazione IRCCS Policlinico San Matteo in Pavia, Italy.

He and his colleagues divided patients into 4 quartiles according to AdV AAUC, with the third and fourth quartiles reflecting higher, more prolonged AdV viremia.

Rates of all-cause mortality at 6 months (from the first viremia ≥ 1000 copies/mL) were 52% in the fourth quartile, 10% in the third, 7% in the second, and 3% in the first quartile.

Forty percent of patients in the fourth quartile died within 2 months of transplant.

The hazard ratio for mortality was 11.7 in the fourth quartile, 2.7 in the third, and 1.5 in the second, with the first quartile as the reference.

“These data suggest that AdV AAUC is an appropriate endpoint to assess the potential benefits of antiviral therapies for the treatment of adenovirus,” Dr Zecca concluded.

*Data in the abstract differ from the presentation.

and Drug Administration

The US Food and Drug Administration (FDA) has released new information on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).

The agency said it is now aware of 414 cases of BIA-ALCL, which includes 9 patients who died.

In addition, the medical literature suggests that patients with textured breast implants have a lifetime risk of developing BIA-ALCL that ranges from 1 in 3817 to 1 in 30,000.

“The FDA has been closely tracking the relationship between breast implants and a rare type of non-Hodgkin’s lymphoma since we first identified this possible association,” said Binita Ashar, MD, director of the division of surgical devices in the FDA’s Center for Devices and Radiological Health.

“We’ve been working to gather additional information to better characterize and quantify the risk so that patients and providers can have more informed discussions about breast implants. As part of that effort, we are working to update and enhance the information we have on this association, including updating the total number of known cases of BIA-ALCL and the lifetime risk of developing BIA-ALCL as reported in medical literature.”

Reports to FDA

Most of the BIA-ALCL cases reported to the FDA occurred in patients with textured implants (n=242), but 30 occurred in patients with smooth implants. In the remaining 173 cases, the implant surface was not specified.

There were more silicone implants (n=234) than saline implants (n=179), and there was 1 case in which the implant filling was not specified.

The patients’ median age was 53 (range, 24-90), and the median time from last implant to BIA-ALCL diagnosis was 8 years (range, 0-44).

Cases of BIA-ALCL were ALK-negative (n=124) or did not have ALK status specified (n=290). And they were CD30-positive (n=126) or did not have CD30 status specified (n=288).

The most common clinical presentation was seroma (n=203), followed by breast swelling/pain (n=101), peri-implant mass/lump (n=45), and capsular contracture (n=42). In some cases, more than one clinical presentation was listed, and there were 141 cases where clinical presentation was unspecified/uncertain.

Medical literature

The FDA said a “significant body of medical literature” on BIA-ALCL has been published since the agency’s 2011 report on this malignancy.

For the aforementioned lifetime risk estimates—1 case of BIA-ALCL in 3817 to 30,000 individuals with textured implants—the FDA cited 3 sources:

• BIA-ALCL Resources : By the numbers, and what they mean
• Breast Implant–Associated Anaplastic Large Cell Lymphoma in Australia and New Zealand: High-Surface-Area Textured Implants Are Associated with Increased Risk
• Breast Implants and the Risk of Anaplastic Large-Cell Lymphoma in the Breast.

Recommendations, more updates

The FDA said this updated information does not change its recommendations regarding breast implants. The agency said the decision to obtain breast implants should be made based on individual needs and with the most complete information about risks and benefits.

“We hope that this information prompts providers and patients to have important, informed conversations about breast implants and the risk of BIA-ALCL,” Dr Ashar said. “At the same time, we remain committed to working in partnership with all stakeholders to continue to study, understand, and provide updates about this important public health issue.”

The FDA is also updating the content and format of the webpage for the agency’s breast implant post-approval studies to make current information about these studies easier for patients to read and understand.

and Drug Administration

The US Food and Drug Administration (FDA) has released new information on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).

The agency said it is now aware of 414 cases of BIA-ALCL, which includes 9 patients who died.

In addition, the medical literature suggests that patients with textured breast implants have a lifetime risk of developing BIA-ALCL that ranges from 1 in 3817 to 1 in 30,000.

“The FDA has been closely tracking the relationship between breast implants and a rare type of non-Hodgkin’s lymphoma since we first identified this possible association,” said Binita Ashar, MD, director of the division of surgical devices in the FDA’s Center for Devices and Radiological Health.

“We’ve been working to gather additional information to better characterize and quantify the risk so that patients and providers can have more informed discussions about breast implants. As part of that effort, we are working to update and enhance the information we have on this association, including updating the total number of known cases of BIA-ALCL and the lifetime risk of developing BIA-ALCL as reported in medical literature.”

Reports to FDA

Most of the BIA-ALCL cases reported to the FDA occurred in patients with textured implants (n=242), but 30 occurred in patients with smooth implants. In the remaining 173 cases, the implant surface was not specified.

There were more silicone implants (n=234) than saline implants (n=179), and there was 1 case in which the implant filling was not specified.

The patients’ median age was 53 (range, 24-90), and the median time from last implant to BIA-ALCL diagnosis was 8 years (range, 0-44).

Cases of BIA-ALCL were ALK-negative (n=124) or did not have ALK status specified (n=290). And they were CD30-positive (n=126) or did not have CD30 status specified (n=288).

The most common clinical presentation was seroma (n=203), followed by breast swelling/pain (n=101), peri-implant mass/lump (n=45), and capsular contracture (n=42). In some cases, more than one clinical presentation was listed, and there were 141 cases where clinical presentation was unspecified/uncertain.

Medical literature

The FDA said a “significant body of medical literature” on BIA-ALCL has been published since the agency’s 2011 report on this malignancy.

For the aforementioned lifetime risk estimates—1 case of BIA-ALCL in 3817 to 30,000 individuals with textured implants—the FDA cited 3 sources:

• BIA-ALCL Resources : By the numbers, and what they mean
• Breast Implant–Associated Anaplastic Large Cell Lymphoma in Australia and New Zealand: High-Surface-Area Textured Implants Are Associated with Increased Risk
• Breast Implants and the Risk of Anaplastic Large-Cell Lymphoma in the Breast.

Recommendations, more updates

The FDA said this updated information does not change its recommendations regarding breast implants. The agency said the decision to obtain breast implants should be made based on individual needs and with the most complete information about risks and benefits.

“We hope that this information prompts providers and patients to have important, informed conversations about breast implants and the risk of BIA-ALCL,” Dr Ashar said. “At the same time, we remain committed to working in partnership with all stakeholders to continue to study, understand, and provide updates about this important public health issue.”

The FDA is also updating the content and format of the webpage for the agency’s breast implant post-approval studies to make current information about these studies easier for patients to read and understand.

and Drug Administration

The US Food and Drug Administration (FDA) has released new information on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).

The agency said it is now aware of 414 cases of BIA-ALCL, which includes 9 patients who died.

In addition, the medical literature suggests that patients with textured breast implants have a lifetime risk of developing BIA-ALCL that ranges from 1 in 3817 to 1 in 30,000.

“The FDA has been closely tracking the relationship between breast implants and a rare type of non-Hodgkin’s lymphoma since we first identified this possible association,” said Binita Ashar, MD, director of the division of surgical devices in the FDA’s Center for Devices and Radiological Health.

“We’ve been working to gather additional information to better characterize and quantify the risk so that patients and providers can have more informed discussions about breast implants. As part of that effort, we are working to update and enhance the information we have on this association, including updating the total number of known cases of BIA-ALCL and the lifetime risk of developing BIA-ALCL as reported in medical literature.”

Reports to FDA

Most of the BIA-ALCL cases reported to the FDA occurred in patients with textured implants (n=242), but 30 occurred in patients with smooth implants. In the remaining 173 cases, the implant surface was not specified.

There were more silicone implants (n=234) than saline implants (n=179), and there was 1 case in which the implant filling was not specified.

The patients’ median age was 53 (range, 24-90), and the median time from last implant to BIA-ALCL diagnosis was 8 years (range, 0-44).

Cases of BIA-ALCL were ALK-negative (n=124) or did not have ALK status specified (n=290). And they were CD30-positive (n=126) or did not have CD30 status specified (n=288).

The most common clinical presentation was seroma (n=203), followed by breast swelling/pain (n=101), peri-implant mass/lump (n=45), and capsular contracture (n=42). In some cases, more than one clinical presentation was listed, and there were 141 cases where clinical presentation was unspecified/uncertain.

Medical literature

The FDA said a “significant body of medical literature” on BIA-ALCL has been published since the agency’s 2011 report on this malignancy.

For the aforementioned lifetime risk estimates—1 case of BIA-ALCL in 3817 to 30,000 individuals with textured implants—the FDA cited 3 sources:

• BIA-ALCL Resources : By the numbers, and what they mean
• Breast Implant–Associated Anaplastic Large Cell Lymphoma in Australia and New Zealand: High-Surface-Area Textured Implants Are Associated with Increased Risk
• Breast Implants and the Risk of Anaplastic Large-Cell Lymphoma in the Breast.

Recommendations, more updates

The FDA said this updated information does not change its recommendations regarding breast implants. The agency said the decision to obtain breast implants should be made based on individual needs and with the most complete information about risks and benefits.

“We hope that this information prompts providers and patients to have important, informed conversations about breast implants and the risk of BIA-ALCL,” Dr Ashar said. “At the same time, we remain committed to working in partnership with all stakeholders to continue to study, understand, and provide updates about this important public health issue.”

The FDA is also updating the content and format of the webpage for the agency’s breast implant post-approval studies to make current information about these studies easier for patients to read and understand.

The FP considered several possibilities as part of the differential diagnosis: compound nevus, Spitz nevus, dysplastic nevus, fibrous papule, angiokeratoma, and amelanotic melanoma. A shave biopsy identified the lesion as a Spitz nevus.

Spitz nevi are uncommon solitary pink to black colored dome-shaped papules that usually appear in the first 2 decades of life. They have features that are histologically similar to melanoma and some may, in fact, be Spitzoid melanomas. When a Spitz nevus is suspected, the lesion should be biopsied for histopathologic diagnosis. If the diagnosis is confirmed, the typical treatment is to perform a complete excision with clear margins.

In this case, the pathologist noted that the deep margin was positive and recommended a conservative re-excision. The patient was sent to a dermatologist who fully excised the lesion with no complications.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M, Usatine R. Benign nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:945-952.

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

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

The FP considered several possibilities as part of the differential diagnosis: compound nevus, Spitz nevus, dysplastic nevus, fibrous papule, angiokeratoma, and amelanotic melanoma. A shave biopsy identified the lesion as a Spitz nevus.

Spitz nevi are uncommon solitary pink to black colored dome-shaped papules that usually appear in the first 2 decades of life. They have features that are histologically similar to melanoma and some may, in fact, be Spitzoid melanomas. When a Spitz nevus is suspected, the lesion should be biopsied for histopathologic diagnosis. If the diagnosis is confirmed, the typical treatment is to perform a complete excision with clear margins.

In this case, the pathologist noted that the deep margin was positive and recommended a conservative re-excision. The patient was sent to a dermatologist who fully excised the lesion with no complications.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M, Usatine R. Benign nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:945-952.

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

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

The FP considered several possibilities as part of the differential diagnosis: compound nevus, Spitz nevus, dysplastic nevus, fibrous papule, angiokeratoma, and amelanotic melanoma. A shave biopsy identified the lesion as a Spitz nevus.

Spitz nevi are uncommon solitary pink to black colored dome-shaped papules that usually appear in the first 2 decades of life. They have features that are histologically similar to melanoma and some may, in fact, be Spitzoid melanomas. When a Spitz nevus is suspected, the lesion should be biopsied for histopathologic diagnosis. If the diagnosis is confirmed, the typical treatment is to perform a complete excision with clear margins.

In this case, the pathologist noted that the deep margin was positive and recommended a conservative re-excision. The patient was sent to a dermatologist who fully excised the lesion with no complications.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M, Usatine R. Benign nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:945-952.

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

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