NASHVILLE, TENN. – By 2010, U.S. octogenarians with acute ischemic stroke received intravenous thrombolytic treatment about as often as younger patients, showing that a sharp, age-related disparity in thrombolytic use a decade before had disappeared, based on comprehensive national data.

The 2010 data from the Nationwide Inpatient Sample further showed that the sex-based disparity in treatment with intravenous tissue plasminogen activator (TPA) seen in 2000 resolved as well from 2000 to 2010, but other disparities worsened with declines during the period in use of TPA at rural hospitals relative to urban hospitals and at nonteaching hospitals, compared with teaching hospitals, Dr. Michelle P. Lin said at the International Stroke Conference.

Perhaps most importantly, the statistics showed a “dramatic” increase in TPA use among all age groups during the decade ending in 2010, when thrombolytic therapy was administered to 3.5%-3.9% of adult patients regardless of their age, said Dr. Lin of the department of neurology at the University of Southern California in Los Angeles. In 2000, U.S. patients received TPA at less than a third of that rate.

Low TPA use in 2000 among patients aged 80 or older in part reflected the low number of octogenarians enrolled in the trials that documented the safety and efficacy of TPA for acute ischemicstroke patients, Dr. Lin said at the International Stroke Conference, sponsored by the American Heart Association.

Data from the National Inpatient Sample included information on the treatment received by 5,932,175 patients with acute ischemic stroke at more than 1,000 U.S. hospitals during 2000-2010. The age breakdown of the nearly 6 millionpatients showed 28% were aged 18-64 years, 37% were65-79, and 35% were 80 years or older.

In 2000, medical staffs administered intravenous treatment with TPA to 1.02% of these patients aged 18-64 years, 0.92% of patients aged 65-79 years, and 0.47% of patients aged 80 or older. By 2010, the annual rates of TPA use ran 3.61% in those 18-64 years, 3.87% among those 65-79 years, and 3.55% in patients 80 years or older. In an adjusted analysis, this translated into a greater than threefold increase in TPA use among the 18- to 64-year-olds, a nearly fourfold rise in patients 65-79 years, and a nearly sevenfold jump among those 80 or older, a 24% average annual increased rate among the oldest patients, who averaged 86 years old, Dr. Lin reported.

The data also showed that among the octogenarians during 2000-2005, TPA use in women lagged behind use in men by a relative 15%, but this completely disappeared during 2006-2010, when usage rates in men and women evened out. TPA use among African Americans, Hispanics, and Asians, compared with whites, remained significantly below the rate in whites throughout the decade, although the extent of the disparity narrowed for African Americans and Asians during the second half of the decade, compared with the first half.

Dr. Lin and her associates also analyzed TPA use relative to the demographic setting of the hospital and its teaching status. During 2000-2010, the relative usage of TPA at rural hospitals, compared with urban hospitals, fell from 65% of the comparator level to 36%. Among nonteaching hospitals, the rate of TPA use dropped from 52% of the teaching hospitals’ level to 49%.

Dr. Lin said she had no relevant financial disclosures.

[email protected]
On Twitter @mitchelzoler

NASHVILLE, TENN. – By 2010, U.S. octogenarians with acute ischemic stroke received intravenous thrombolytic treatment about as often as younger patients, showing that a sharp, age-related disparity in thrombolytic use a decade before had disappeared, based on comprehensive national data.

The 2010 data from the Nationwide Inpatient Sample further showed that the sex-based disparity in treatment with intravenous tissue plasminogen activator (TPA) seen in 2000 resolved as well from 2000 to 2010, but other disparities worsened with declines during the period in use of TPA at rural hospitals relative to urban hospitals and at nonteaching hospitals, compared with teaching hospitals, Dr. Michelle P. Lin said at the International Stroke Conference.

Perhaps most importantly, the statistics showed a “dramatic” increase in TPA use among all age groups during the decade ending in 2010, when thrombolytic therapy was administered to 3.5%-3.9% of adult patients regardless of their age, said Dr. Lin of the department of neurology at the University of Southern California in Los Angeles. In 2000, U.S. patients received TPA at less than a third of that rate.

Low TPA use in 2000 among patients aged 80 or older in part reflected the low number of octogenarians enrolled in the trials that documented the safety and efficacy of TPA for acute ischemicstroke patients, Dr. Lin said at the International Stroke Conference, sponsored by the American Heart Association.

Data from the National Inpatient Sample included information on the treatment received by 5,932,175 patients with acute ischemic stroke at more than 1,000 U.S. hospitals during 2000-2010. The age breakdown of the nearly 6 millionpatients showed 28% were aged 18-64 years, 37% were65-79, and 35% were 80 years or older.

In 2000, medical staffs administered intravenous treatment with TPA to 1.02% of these patients aged 18-64 years, 0.92% of patients aged 65-79 years, and 0.47% of patients aged 80 or older. By 2010, the annual rates of TPA use ran 3.61% in those 18-64 years, 3.87% among those 65-79 years, and 3.55% in patients 80 years or older. In an adjusted analysis, this translated into a greater than threefold increase in TPA use among the 18- to 64-year-olds, a nearly fourfold rise in patients 65-79 years, and a nearly sevenfold jump among those 80 or older, a 24% average annual increased rate among the oldest patients, who averaged 86 years old, Dr. Lin reported.

The data also showed that among the octogenarians during 2000-2005, TPA use in women lagged behind use in men by a relative 15%, but this completely disappeared during 2006-2010, when usage rates in men and women evened out. TPA use among African Americans, Hispanics, and Asians, compared with whites, remained significantly below the rate in whites throughout the decade, although the extent of the disparity narrowed for African Americans and Asians during the second half of the decade, compared with the first half.

Dr. Lin and her associates also analyzed TPA use relative to the demographic setting of the hospital and its teaching status. During 2000-2010, the relative usage of TPA at rural hospitals, compared with urban hospitals, fell from 65% of the comparator level to 36%. Among nonteaching hospitals, the rate of TPA use dropped from 52% of the teaching hospitals’ level to 49%.

Dr. Lin said she had no relevant financial disclosures.

[email protected]
On Twitter @mitchelzoler

NASHVILLE, TENN. – By 2010, U.S. octogenarians with acute ischemic stroke received intravenous thrombolytic treatment about as often as younger patients, showing that a sharp, age-related disparity in thrombolytic use a decade before had disappeared, based on comprehensive national data.

The 2010 data from the Nationwide Inpatient Sample further showed that the sex-based disparity in treatment with intravenous tissue plasminogen activator (TPA) seen in 2000 resolved as well from 2000 to 2010, but other disparities worsened with declines during the period in use of TPA at rural hospitals relative to urban hospitals and at nonteaching hospitals, compared with teaching hospitals, Dr. Michelle P. Lin said at the International Stroke Conference.

Perhaps most importantly, the statistics showed a “dramatic” increase in TPA use among all age groups during the decade ending in 2010, when thrombolytic therapy was administered to 3.5%-3.9% of adult patients regardless of their age, said Dr. Lin of the department of neurology at the University of Southern California in Los Angeles. In 2000, U.S. patients received TPA at less than a third of that rate.

Low TPA use in 2000 among patients aged 80 or older in part reflected the low number of octogenarians enrolled in the trials that documented the safety and efficacy of TPA for acute ischemicstroke patients, Dr. Lin said at the International Stroke Conference, sponsored by the American Heart Association.

Data from the National Inpatient Sample included information on the treatment received by 5,932,175 patients with acute ischemic stroke at more than 1,000 U.S. hospitals during 2000-2010. The age breakdown of the nearly 6 millionpatients showed 28% were aged 18-64 years, 37% were65-79, and 35% were 80 years or older.

In 2000, medical staffs administered intravenous treatment with TPA to 1.02% of these patients aged 18-64 years, 0.92% of patients aged 65-79 years, and 0.47% of patients aged 80 or older. By 2010, the annual rates of TPA use ran 3.61% in those 18-64 years, 3.87% among those 65-79 years, and 3.55% in patients 80 years or older. In an adjusted analysis, this translated into a greater than threefold increase in TPA use among the 18- to 64-year-olds, a nearly fourfold rise in patients 65-79 years, and a nearly sevenfold jump among those 80 or older, a 24% average annual increased rate among the oldest patients, who averaged 86 years old, Dr. Lin reported.

The data also showed that among the octogenarians during 2000-2005, TPA use in women lagged behind use in men by a relative 15%, but this completely disappeared during 2006-2010, when usage rates in men and women evened out. TPA use among African Americans, Hispanics, and Asians, compared with whites, remained significantly below the rate in whites throughout the decade, although the extent of the disparity narrowed for African Americans and Asians during the second half of the decade, compared with the first half.

Dr. Lin and her associates also analyzed TPA use relative to the demographic setting of the hospital and its teaching status. During 2000-2010, the relative usage of TPA at rural hospitals, compared with urban hospitals, fell from 65% of the comparator level to 36%. Among nonteaching hospitals, the rate of TPA use dropped from 52% of the teaching hospitals’ level to 49%.

Dr. Lin said she had no relevant financial disclosures.

[email protected]
On Twitter @mitchelzoler

For patients with secondary acute myeloid leukemia, induction therapy with cytarabine in combination with amonafide L-malate did not improve complete remission rates over the standard treatment of cytarabine and daunorubicin, investigators reported online March 2 in the Journal of Clinical Oncology.

Between January 2008 and August 2010, 433 patients with previously untreated secondary AML were randomly assigned to receive an intravenous infusion of cytarabine once per day for 7 days, plus either amonafide or daunorubicin for 4 days. The complete remission rate was 46% in the amonafide-plus-cytarabine group and 45% in the daunorubicin-plus-cytarabine group (P = .81), reported Dr. Richard M. Stone of Dana-Farber Cancer Institute, Boston, and associates.

“Although amonafide does not seem to provide benefit over standard induction therapy with daunorubicin, analyses of the data from this clinical trial may provide critical background information for tests of subsequent drugs that may have promise in this important disease subgroup, such as the liposomal-encapsulated daunorubicin/cytarabine CPX-351, the nuclear export inhibitor KPT-330, or the BCL-2 antagonist ABT-199,” they concluded.

Read the complete article here: (doi:10.1200/JCO.2014.57.0952).

For patients with secondary acute myeloid leukemia, induction therapy with cytarabine in combination with amonafide L-malate did not improve complete remission rates over the standard treatment of cytarabine and daunorubicin, investigators reported online March 2 in the Journal of Clinical Oncology.

Between January 2008 and August 2010, 433 patients with previously untreated secondary AML were randomly assigned to receive an intravenous infusion of cytarabine once per day for 7 days, plus either amonafide or daunorubicin for 4 days. The complete remission rate was 46% in the amonafide-plus-cytarabine group and 45% in the daunorubicin-plus-cytarabine group (P = .81), reported Dr. Richard M. Stone of Dana-Farber Cancer Institute, Boston, and associates.

“Although amonafide does not seem to provide benefit over standard induction therapy with daunorubicin, analyses of the data from this clinical trial may provide critical background information for tests of subsequent drugs that may have promise in this important disease subgroup, such as the liposomal-encapsulated daunorubicin/cytarabine CPX-351, the nuclear export inhibitor KPT-330, or the BCL-2 antagonist ABT-199,” they concluded.

Read the complete article here: (doi:10.1200/JCO.2014.57.0952).

For patients with secondary acute myeloid leukemia, induction therapy with cytarabine in combination with amonafide L-malate did not improve complete remission rates over the standard treatment of cytarabine and daunorubicin, investigators reported online March 2 in the Journal of Clinical Oncology.

Between January 2008 and August 2010, 433 patients with previously untreated secondary AML were randomly assigned to receive an intravenous infusion of cytarabine once per day for 7 days, plus either amonafide or daunorubicin for 4 days. The complete remission rate was 46% in the amonafide-plus-cytarabine group and 45% in the daunorubicin-plus-cytarabine group (P = .81), reported Dr. Richard M. Stone of Dana-Farber Cancer Institute, Boston, and associates.

“Although amonafide does not seem to provide benefit over standard induction therapy with daunorubicin, analyses of the data from this clinical trial may provide critical background information for tests of subsequent drugs that may have promise in this important disease subgroup, such as the liposomal-encapsulated daunorubicin/cytarabine CPX-351, the nuclear export inhibitor KPT-330, or the BCL-2 antagonist ABT-199,” they concluded.

Read the complete article here: (doi:10.1200/JCO.2014.57.0952).

NASHVILLE, TENN. – When acute ischemic stroke patients undergo an emergency endovascular procedure is it best done with general anesthesia or nongeneral anesthesia?

A post hoc analysis of data collected by a Dutch randomized, controlled trial of intra-arterial therapy suggested that nongeneral anesthesia was associated with substantially better patient outcomes, and the findings convinced the Dutch investigators who ran the study to stick with nongeneral anesthesia as their default approach.

In MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) (N. Engl. J. Med. 2015;372:11-20), 216 acute ischemic stroke patients underwent intra-arterial treatment following randomization. Among these patients, 79 were treated with general anesthesia and 137 with nongeneral anesthesia. The anesthesia choice was made on a case-by-case basis by each participating interventionalist.

The study’s primary endpoint – 90-day status rated as a good function based on a modified Rankin sale score of 0-2 – occurred in 38% of the intra-arterial patients treated with nongeneral anesthesia, 23% of the intra-arterial patients treated with general anesthesia, and 19% among the control patients who received standard treatment without intra-arterial intervention.

Mitchel L. Zoler/Frontline Medical News

“The effect on outcome that we found with intra-arterial treatment in MR CLEAN was not observed in the subgroup of patients treated with general anesthesia,” said Dr. Olvert A. Berkhemer at the International Stroke Conference. The analysis also showed that patients in the general and nongeneral anesthesia subgroups had similar stroke severity as measured by their National Institutes of Health Stroke Scale score, said Dr. Berkhemer, a researcher at the Academic Medical Center in Amsterdam.

But U.S. stroke specialists who heard the report cautioned that unidentified confounders might explain the results, and they also expressed skepticism that the Dutch observations would deter U.S. interventionalists from continuing to use general anesthesia when they perform endovascular procedures.

“The big concern [about this analysis] is that there may have been some things about the general anesthesia patients that they did not account for. I suspect there is a huge bias, that general anesthesia patients were sicker,” said Dr. Bruce Ovbiagele, professor and chief of neurology at the Medical University of South Carolina in Charleston. “At my institution they have used nongeneral anesthesia, but I have been at other places where they usually use general anesthesia; it is variable,” Dr. Ovbiagele added.

Mitchel L. Zoler/Frontline Medical News

Dr. Berkhemer’s analysis also showed that general anesthesia linked with a delayed start to treatment, but without resulting in a significant difference in time to reperfusion. He noted that “sometimes you cannot do the procedure without general anesthesia,” and in MR CLEAN 6 of the 137 intra-arterial patients who started with nongeneral anesthesia eventually received general anesthesia because of discomfort and pain, Dr. Berkhemer said at the conference, sponsored by the American Heart Association.

He speculated that patients who did not receive general anesthesia did better because they did not undergo acute episodes of reduced blood pressure caused by the hypotensive effect of general anesthesia.

Mitchel L. Zoler/Frontline Medical News

The findings reinforced the approach already used in most of the Dutch centers that participated in MR CLEAN, where nongeneral anesthesia is preferred when possible. “In our center we always use nongeneral anesthesia, we are happy with that and we are not going to change,” said Dr. Diederik W.J. Dippel, lead investigator of MR CLEAN and professor of neurology at Erasmus University Medical Center in Rotterdam, The Netherlands. This prejudice against general anesthesia would make it hard to run a trial in The Netherlands that matched the two anesthesia approaches against each other, Dr. Dippel added.

[email protected]

On Twitter @mitchelzoler

NASHVILLE, TENN. – When acute ischemic stroke patients undergo an emergency endovascular procedure is it best done with general anesthesia or nongeneral anesthesia?

A post hoc analysis of data collected by a Dutch randomized, controlled trial of intra-arterial therapy suggested that nongeneral anesthesia was associated with substantially better patient outcomes, and the findings convinced the Dutch investigators who ran the study to stick with nongeneral anesthesia as their default approach.

In MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) (N. Engl. J. Med. 2015;372:11-20), 216 acute ischemic stroke patients underwent intra-arterial treatment following randomization. Among these patients, 79 were treated with general anesthesia and 137 with nongeneral anesthesia. The anesthesia choice was made on a case-by-case basis by each participating interventionalist.

The study’s primary endpoint – 90-day status rated as a good function based on a modified Rankin sale score of 0-2 – occurred in 38% of the intra-arterial patients treated with nongeneral anesthesia, 23% of the intra-arterial patients treated with general anesthesia, and 19% among the control patients who received standard treatment without intra-arterial intervention.

Mitchel L. Zoler/Frontline Medical News

“The effect on outcome that we found with intra-arterial treatment in MR CLEAN was not observed in the subgroup of patients treated with general anesthesia,” said Dr. Olvert A. Berkhemer at the International Stroke Conference. The analysis also showed that patients in the general and nongeneral anesthesia subgroups had similar stroke severity as measured by their National Institutes of Health Stroke Scale score, said Dr. Berkhemer, a researcher at the Academic Medical Center in Amsterdam.

But U.S. stroke specialists who heard the report cautioned that unidentified confounders might explain the results, and they also expressed skepticism that the Dutch observations would deter U.S. interventionalists from continuing to use general anesthesia when they perform endovascular procedures.

“The big concern [about this analysis] is that there may have been some things about the general anesthesia patients that they did not account for. I suspect there is a huge bias, that general anesthesia patients were sicker,” said Dr. Bruce Ovbiagele, professor and chief of neurology at the Medical University of South Carolina in Charleston. “At my institution they have used nongeneral anesthesia, but I have been at other places where they usually use general anesthesia; it is variable,” Dr. Ovbiagele added.

Mitchel L. Zoler/Frontline Medical News

Dr. Berkhemer’s analysis also showed that general anesthesia linked with a delayed start to treatment, but without resulting in a significant difference in time to reperfusion. He noted that “sometimes you cannot do the procedure without general anesthesia,” and in MR CLEAN 6 of the 137 intra-arterial patients who started with nongeneral anesthesia eventually received general anesthesia because of discomfort and pain, Dr. Berkhemer said at the conference, sponsored by the American Heart Association.

He speculated that patients who did not receive general anesthesia did better because they did not undergo acute episodes of reduced blood pressure caused by the hypotensive effect of general anesthesia.

Mitchel L. Zoler/Frontline Medical News

The findings reinforced the approach already used in most of the Dutch centers that participated in MR CLEAN, where nongeneral anesthesia is preferred when possible. “In our center we always use nongeneral anesthesia, we are happy with that and we are not going to change,” said Dr. Diederik W.J. Dippel, lead investigator of MR CLEAN and professor of neurology at Erasmus University Medical Center in Rotterdam, The Netherlands. This prejudice against general anesthesia would make it hard to run a trial in The Netherlands that matched the two anesthesia approaches against each other, Dr. Dippel added.

[email protected]

On Twitter @mitchelzoler

NASHVILLE, TENN. – When acute ischemic stroke patients undergo an emergency endovascular procedure is it best done with general anesthesia or nongeneral anesthesia?

A post hoc analysis of data collected by a Dutch randomized, controlled trial of intra-arterial therapy suggested that nongeneral anesthesia was associated with substantially better patient outcomes, and the findings convinced the Dutch investigators who ran the study to stick with nongeneral anesthesia as their default approach.

In MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) (N. Engl. J. Med. 2015;372:11-20), 216 acute ischemic stroke patients underwent intra-arterial treatment following randomization. Among these patients, 79 were treated with general anesthesia and 137 with nongeneral anesthesia. The anesthesia choice was made on a case-by-case basis by each participating interventionalist.

The study’s primary endpoint – 90-day status rated as a good function based on a modified Rankin sale score of 0-2 – occurred in 38% of the intra-arterial patients treated with nongeneral anesthesia, 23% of the intra-arterial patients treated with general anesthesia, and 19% among the control patients who received standard treatment without intra-arterial intervention.

Mitchel L. Zoler/Frontline Medical News

“The effect on outcome that we found with intra-arterial treatment in MR CLEAN was not observed in the subgroup of patients treated with general anesthesia,” said Dr. Olvert A. Berkhemer at the International Stroke Conference. The analysis also showed that patients in the general and nongeneral anesthesia subgroups had similar stroke severity as measured by their National Institutes of Health Stroke Scale score, said Dr. Berkhemer, a researcher at the Academic Medical Center in Amsterdam.

But U.S. stroke specialists who heard the report cautioned that unidentified confounders might explain the results, and they also expressed skepticism that the Dutch observations would deter U.S. interventionalists from continuing to use general anesthesia when they perform endovascular procedures.

“The big concern [about this analysis] is that there may have been some things about the general anesthesia patients that they did not account for. I suspect there is a huge bias, that general anesthesia patients were sicker,” said Dr. Bruce Ovbiagele, professor and chief of neurology at the Medical University of South Carolina in Charleston. “At my institution they have used nongeneral anesthesia, but I have been at other places where they usually use general anesthesia; it is variable,” Dr. Ovbiagele added.

Mitchel L. Zoler/Frontline Medical News

Dr. Berkhemer’s analysis also showed that general anesthesia linked with a delayed start to treatment, but without resulting in a significant difference in time to reperfusion. He noted that “sometimes you cannot do the procedure without general anesthesia,” and in MR CLEAN 6 of the 137 intra-arterial patients who started with nongeneral anesthesia eventually received general anesthesia because of discomfort and pain, Dr. Berkhemer said at the conference, sponsored by the American Heart Association.

He speculated that patients who did not receive general anesthesia did better because they did not undergo acute episodes of reduced blood pressure caused by the hypotensive effect of general anesthesia.

Mitchel L. Zoler/Frontline Medical News

The findings reinforced the approach already used in most of the Dutch centers that participated in MR CLEAN, where nongeneral anesthesia is preferred when possible. “In our center we always use nongeneral anesthesia, we are happy with that and we are not going to change,” said Dr. Diederik W.J. Dippel, lead investigator of MR CLEAN and professor of neurology at Erasmus University Medical Center in Rotterdam, The Netherlands. This prejudice against general anesthesia would make it hard to run a trial in The Netherlands that matched the two anesthesia approaches against each other, Dr. Dippel added.

[email protected]

On Twitter @mitchelzoler

DAVID PRESSEL, MD, PHD, FHM, medical director of inpatient services at Nemours Children’s Health System, talks about the nature of violence in hospitals and a training program he has helped put into place at his center.

DAVID PRESSEL, MD, PHD, FHM, medical director of inpatient services at Nemours Children’s Health System, talks about the nature of violence in hospitals and a training program he has helped put into place at his center.

DAVID PRESSEL, MD, PHD, FHM, medical director of inpatient services at Nemours Children’s Health System, talks about the nature of violence in hospitals and a training program he has helped put into place at his center.

DAVID LICHTMAN, PA, a hospitalist and director of the Johns Hopkins Central Procedure Service, explains the complicated set of factors used by

individual hospitals to determine which procedures fall under the scope of their HM practitioners.

DAVID LICHTMAN, PA, a hospitalist and director of the Johns Hopkins Central Procedure Service, explains the complicated set of factors used by

individual hospitals to determine which procedures fall under the scope of their HM practitioners.

DAVID LICHTMAN, PA, a hospitalist and director of the Johns Hopkins Central Procedure Service, explains the complicated set of factors used by

individual hospitals to determine which procedures fall under the scope of their HM practitioners.

Although patients with blood clots are oftentimes not admitted to the hospital, there are some exceptions. Monal Shah, MD, physician advisor for Parkland Hospital in Dallas, Texas, and the former section head of hospital medicine at the University of Texas Southwestern Medical Center, discusses some exceptions.

Although patients with blood clots are oftentimes not admitted to the hospital, there are some exceptions. Monal Shah, MD, physician advisor for Parkland Hospital in Dallas, Texas, and the former section head of hospital medicine at the University of Texas Southwestern Medical Center, discusses some exceptions.

Although patients with blood clots are oftentimes not admitted to the hospital, there are some exceptions. Monal Shah, MD, physician advisor for Parkland Hospital in Dallas, Texas, and the former section head of hospital medicine at the University of Texas Southwestern Medical Center, discusses some exceptions.

Adam E. Fall, MD, SFHM, who recently worked as the senior regional medical director for hospital medicine at TeamHealth in Chattanooga, Tenn., discusses the importance of allowing nuance and gradation to govern patient care in the treatment of thromboembolism in an era where hospitalists can be overly reliant on electronic medical records.

Adam E. Fall, MD, SFHM, who recently worked as the senior regional medical director for hospital medicine at TeamHealth in Chattanooga, Tenn., discusses the importance of allowing nuance and gradation to govern patient care in the treatment of thromboembolism in an era where hospitalists can be overly reliant on electronic medical records.

Adam E. Fall, MD, SFHM, who recently worked as the senior regional medical director for hospital medicine at TeamHealth in Chattanooga, Tenn., discusses the importance of allowing nuance and gradation to govern patient care in the treatment of thromboembolism in an era where hospitalists can be overly reliant on electronic medical records.

David Lichtman, PA, director of the Johns Hopkins Central Procedure Service in Baltimore, Md., says bedside procedure training should be consistent and thorough, regardless of whether the trainee is a medical student, a resident, a fellow, or an established physician. He is a strong advocate for training that includes well-designed computer coursework, evaluates practitioners from start to finish, and demonstrates that they are meeting established benchmarks.

“That’s what keeps patients safe,” he says.

Experienced, capable, and proven educators are also critical.

“Let’s face it: Not everybody is a very good teacher,” he adds.

Currently, many medical residents can do rotations that will give them hands-on experience. But some physicians question why certain procedures are still being taught to internal medicine residents if the ABIM no longer requires hands-on experience. Other programs may simply lack the resources, including experienced supervisors, to provide proper training.

The demand for more training is clearly there, however. Sally Wang, MD, FHM, director of procedure education at Brigham and Women’s Hospital and a clinical instructor at Harvard Medical School in Boston, co-leads the procedures pre-course at the SHM annual meeting. She compares the logistically complicated event to throwing a wedding. It consistently sells out despite having doubled in size, to 60 slots for a basic procedure course and 60 slots for a second course that emphasizes ultrasound. At the HM14 pre-course in Las Vegas, Dr. Wang counted enough people on the waiting list to fill an additional course.

“It was mind-boggling,” she says.

Several companies have taken notice of the pent-up demand and are offering their own courses and workshops. Joshua Lenchus, DO, RPh, FACP, SFHM, medical director of the University of Miami-Jackson Memorial Hospital’s procedure service, and others see many of these offerings as introductions only, however. At the University of Miami, he says, his rigorous, simulation-based invasive bedside procedures curriculum is mandatory for all internal medicine residents. The curriculum includes central line, thoracentesis, paracentesis, lumbar puncture, and sometimes arthrocentesis as its core procedures, though Dr. Lenchus says others can easily be added. This fall, for instance, he plans to add chest tube and arterial line placement.

He notes a dramatic reduction in central line placement and thoracentesis complications after his team began performing them to the “four pillars” of his program. Rigorous simulation-based training, strict adherence to a critical skills checklist, consistent use of ultrasound, and direct supervision can form a very effective bundle of safety measures, he says, just like a combination of seat belts, speed reduction, and other precautions can lead to fewer automobile-associated injuries and deaths. TH

David Lichtman, PA, director of the Johns Hopkins Central Procedure Service in Baltimore, Md., says bedside procedure training should be consistent and thorough, regardless of whether the trainee is a medical student, a resident, a fellow, or an established physician. He is a strong advocate for training that includes well-designed computer coursework, evaluates practitioners from start to finish, and demonstrates that they are meeting established benchmarks.

“That’s what keeps patients safe,” he says.

Experienced, capable, and proven educators are also critical.

“Let’s face it: Not everybody is a very good teacher,” he adds.

Currently, many medical residents can do rotations that will give them hands-on experience. But some physicians question why certain procedures are still being taught to internal medicine residents if the ABIM no longer requires hands-on experience. Other programs may simply lack the resources, including experienced supervisors, to provide proper training.

The demand for more training is clearly there, however. Sally Wang, MD, FHM, director of procedure education at Brigham and Women’s Hospital and a clinical instructor at Harvard Medical School in Boston, co-leads the procedures pre-course at the SHM annual meeting. She compares the logistically complicated event to throwing a wedding. It consistently sells out despite having doubled in size, to 60 slots for a basic procedure course and 60 slots for a second course that emphasizes ultrasound. At the HM14 pre-course in Las Vegas, Dr. Wang counted enough people on the waiting list to fill an additional course.

“It was mind-boggling,” she says.

Several companies have taken notice of the pent-up demand and are offering their own courses and workshops. Joshua Lenchus, DO, RPh, FACP, SFHM, medical director of the University of Miami-Jackson Memorial Hospital’s procedure service, and others see many of these offerings as introductions only, however. At the University of Miami, he says, his rigorous, simulation-based invasive bedside procedures curriculum is mandatory for all internal medicine residents. The curriculum includes central line, thoracentesis, paracentesis, lumbar puncture, and sometimes arthrocentesis as its core procedures, though Dr. Lenchus says others can easily be added. This fall, for instance, he plans to add chest tube and arterial line placement.

He notes a dramatic reduction in central line placement and thoracentesis complications after his team began performing them to the “four pillars” of his program. Rigorous simulation-based training, strict adherence to a critical skills checklist, consistent use of ultrasound, and direct supervision can form a very effective bundle of safety measures, he says, just like a combination of seat belts, speed reduction, and other precautions can lead to fewer automobile-associated injuries and deaths. TH

David Lichtman, PA, director of the Johns Hopkins Central Procedure Service in Baltimore, Md., says bedside procedure training should be consistent and thorough, regardless of whether the trainee is a medical student, a resident, a fellow, or an established physician. He is a strong advocate for training that includes well-designed computer coursework, evaluates practitioners from start to finish, and demonstrates that they are meeting established benchmarks.

“That’s what keeps patients safe,” he says.

Experienced, capable, and proven educators are also critical.

“Let’s face it: Not everybody is a very good teacher,” he adds.

Currently, many medical residents can do rotations that will give them hands-on experience. But some physicians question why certain procedures are still being taught to internal medicine residents if the ABIM no longer requires hands-on experience. Other programs may simply lack the resources, including experienced supervisors, to provide proper training.

The demand for more training is clearly there, however. Sally Wang, MD, FHM, director of procedure education at Brigham and Women’s Hospital and a clinical instructor at Harvard Medical School in Boston, co-leads the procedures pre-course at the SHM annual meeting. She compares the logistically complicated event to throwing a wedding. It consistently sells out despite having doubled in size, to 60 slots for a basic procedure course and 60 slots for a second course that emphasizes ultrasound. At the HM14 pre-course in Las Vegas, Dr. Wang counted enough people on the waiting list to fill an additional course.

“It was mind-boggling,” she says.

Several companies have taken notice of the pent-up demand and are offering their own courses and workshops. Joshua Lenchus, DO, RPh, FACP, SFHM, medical director of the University of Miami-Jackson Memorial Hospital’s procedure service, and others see many of these offerings as introductions only, however. At the University of Miami, he says, his rigorous, simulation-based invasive bedside procedures curriculum is mandatory for all internal medicine residents. The curriculum includes central line, thoracentesis, paracentesis, lumbar puncture, and sometimes arthrocentesis as its core procedures, though Dr. Lenchus says others can easily be added. This fall, for instance, he plans to add chest tube and arterial line placement.

He notes a dramatic reduction in central line placement and thoracentesis complications after his team began performing them to the “four pillars” of his program. Rigorous simulation-based training, strict adherence to a critical skills checklist, consistent use of ultrasound, and direct supervision can form a very effective bundle of safety measures, he says, just like a combination of seat belts, speed reduction, and other precautions can lead to fewer automobile-associated injuries and deaths. TH

Saad S. Kenderian

Photo courtesy of

BMT Tandem Meetings

SAN DIEGO—Researchers have developed a “biodegradable” chimeric antigen receptor (CAR) T-cell therapy that could potentially serve as a preparative regimen for acute myeloid leukemia (AML) patients undergoing allogeneic transplant.

The team created CAR T cells that target CD33 (CART33) and modified them with RNA so the cells would stop expressing CARs over time.

In mouse models of AML, the RNA-CART33 cells had an antileukemic effect and induced myeloablation.

The cells also stopped expressing CARs by the 2-week mark, which would allow for engraftment after allogeneic transplant, according to the researchers.

Saad S. Kenderian, MD, of the University of Pennsylvania in Philadelphia, presented this research at the 2015 BMT Tandem Meetings as one of the meeting’s “Best Abstracts” (abstract 1). The research was funded by Novartis.

“Allogeneic transplantation is the only potentially curative option in relapsed/refractory AML,” Dr Kenderian noted. “Outcomes are poor if patients are transplanted in residual disease  . . . , and these patients are often considered transplant-ineligible. Therefore, novel therapies are desperately needed.”

With this in mind, Dr Kenderian and his colleagues set out to develop a CAR T-cell therapy targeting CD33, which is expressed on AML blasts.

The researchers created a CAR from the anti-CD33 single-chain fragment variable of gemtuzumab ozogamicin, 41BB costimulation, CD3ζ signaling domain, and a lentiviral (LV) vector. They transduced T cells with this construct and expanded them in culture using anti-CD3/CD28 magnetic beads.

The team then tested these CART33 cells in NSGS mice engrafted with primary AML blasts. The mice received CART33 cells, another CAR T-cell therapy known as CART123, or control T cells.

At 4 weeks, mice that had received CART33 or CART123 cells were entirely leukemia-free, but the disease continued to progress in mice that received control T cells.

Likewise, when the experiment ended at 200 days, survival was 100% among mice that received CART33 or CART123, but all of the control mice had died. And at 200 days, CAR T cells were still circulating in the CART33- and CART123-treated mice.

Next, the researchers administered CART33 cells to HIS-NSG mice engrafted with human bone marrow and found the treatment resulted in myeloablation. There was a significant reduction of CD34-positive cells in mice that received CART33 compared to mice that received control T cells or no treatment.

“So based on our preclinical data, when we treat refractory AML with lentivirally transduced CART33, that will result in myeloablation, eradication of AML, and persistence of these CARs,” Dr Kenderian said.

“If allogeneic transplantation is performed at this aplastic stage, it will likely lead to rejection of the graft by persisting CAR therapy, which also means that elimination of CARs is necessary prior to stem cell infusion.”

So the researchers decided to create a transiently expressed, mRNA-modified CAR based on CART33. They electroporated T cells with this construct, and the cells expressed CARs for up to 6 days.

In experiments with the MOLM14 cell line, RNA-modified CART33 cells exhibited transient but comparable killing ability as LV-transduced CART33.

The researchers then tested RNA-CART33 in combination with chemotherapy in vivo. They transplanted NSG mice with MOLM14 and treated them with cyclophosphamide plus RNA-CART33 or cyclophosphamide plus control T cells.

Combination RNA-CART33 and chemotherapy prompted stronger, more durable antileukemic activity than cyclophosphamide and control T cells. Furthermore, there was a significant improvement in survival among RNA-CART33-treated mice (P=0.01).

Finally, Dr Kenderian and his colleagues tested the effect of RNA-CART33 on hematopoiesis. The team treated NSGS mice with busulfan and transplanted them with T-cell-depleted bone marrow. Following engraftment, mice received RNA-CART33 cells, LV-CART33 cells, or control T cells.

The researchers followed the mice for 2 weeks and found that both RNA-CART33 and LV-CART33 induced myeloablation. And at 14 days, LV-CART33-treated mice were still expressing CARs, but RNA-CART33-treated mice were not.

“Based on our preclinical data, if we treat refractory AML with RNA-modified CART33, that results in myeloablation, anti-AML activity, and biodegradable, non-persisting CARs,” Dr Kenderian summarized.

“If allogeneic transplantation follows at this stage, it will likely lead to engraftment. Therefore, we conclude from this study that RNA-CART33 could be incorporated in novel conditioning regimens and will be tested in pilot phase 1 studies.”

Saad S. Kenderian

Photo courtesy of

BMT Tandem Meetings

SAN DIEGO—Researchers have developed a “biodegradable” chimeric antigen receptor (CAR) T-cell therapy that could potentially serve as a preparative regimen for acute myeloid leukemia (AML) patients undergoing allogeneic transplant.

The team created CAR T cells that target CD33 (CART33) and modified them with RNA so the cells would stop expressing CARs over time.

In mouse models of AML, the RNA-CART33 cells had an antileukemic effect and induced myeloablation.

The cells also stopped expressing CARs by the 2-week mark, which would allow for engraftment after allogeneic transplant, according to the researchers.

Saad S. Kenderian, MD, of the University of Pennsylvania in Philadelphia, presented this research at the 2015 BMT Tandem Meetings as one of the meeting’s “Best Abstracts” (abstract 1). The research was funded by Novartis.

“Allogeneic transplantation is the only potentially curative option in relapsed/refractory AML,” Dr Kenderian noted. “Outcomes are poor if patients are transplanted in residual disease  . . . , and these patients are often considered transplant-ineligible. Therefore, novel therapies are desperately needed.”

With this in mind, Dr Kenderian and his colleagues set out to develop a CAR T-cell therapy targeting CD33, which is expressed on AML blasts.

The researchers created a CAR from the anti-CD33 single-chain fragment variable of gemtuzumab ozogamicin, 41BB costimulation, CD3ζ signaling domain, and a lentiviral (LV) vector. They transduced T cells with this construct and expanded them in culture using anti-CD3/CD28 magnetic beads.

The team then tested these CART33 cells in NSGS mice engrafted with primary AML blasts. The mice received CART33 cells, another CAR T-cell therapy known as CART123, or control T cells.

At 4 weeks, mice that had received CART33 or CART123 cells were entirely leukemia-free, but the disease continued to progress in mice that received control T cells.

Likewise, when the experiment ended at 200 days, survival was 100% among mice that received CART33 or CART123, but all of the control mice had died. And at 200 days, CAR T cells were still circulating in the CART33- and CART123-treated mice.

Next, the researchers administered CART33 cells to HIS-NSG mice engrafted with human bone marrow and found the treatment resulted in myeloablation. There was a significant reduction of CD34-positive cells in mice that received CART33 compared to mice that received control T cells or no treatment.

“So based on our preclinical data, when we treat refractory AML with lentivirally transduced CART33, that will result in myeloablation, eradication of AML, and persistence of these CARs,” Dr Kenderian said.

“If allogeneic transplantation is performed at this aplastic stage, it will likely lead to rejection of the graft by persisting CAR therapy, which also means that elimination of CARs is necessary prior to stem cell infusion.”

So the researchers decided to create a transiently expressed, mRNA-modified CAR based on CART33. They electroporated T cells with this construct, and the cells expressed CARs for up to 6 days.

In experiments with the MOLM14 cell line, RNA-modified CART33 cells exhibited transient but comparable killing ability as LV-transduced CART33.

The researchers then tested RNA-CART33 in combination with chemotherapy in vivo. They transplanted NSG mice with MOLM14 and treated them with cyclophosphamide plus RNA-CART33 or cyclophosphamide plus control T cells.

Combination RNA-CART33 and chemotherapy prompted stronger, more durable antileukemic activity than cyclophosphamide and control T cells. Furthermore, there was a significant improvement in survival among RNA-CART33-treated mice (P=0.01).

Finally, Dr Kenderian and his colleagues tested the effect of RNA-CART33 on hematopoiesis. The team treated NSGS mice with busulfan and transplanted them with T-cell-depleted bone marrow. Following engraftment, mice received RNA-CART33 cells, LV-CART33 cells, or control T cells.

The researchers followed the mice for 2 weeks and found that both RNA-CART33 and LV-CART33 induced myeloablation. And at 14 days, LV-CART33-treated mice were still expressing CARs, but RNA-CART33-treated mice were not.

“Based on our preclinical data, if we treat refractory AML with RNA-modified CART33, that results in myeloablation, anti-AML activity, and biodegradable, non-persisting CARs,” Dr Kenderian summarized.

“If allogeneic transplantation follows at this stage, it will likely lead to engraftment. Therefore, we conclude from this study that RNA-CART33 could be incorporated in novel conditioning regimens and will be tested in pilot phase 1 studies.”

Saad S. Kenderian

Photo courtesy of

BMT Tandem Meetings

SAN DIEGO—Researchers have developed a “biodegradable” chimeric antigen receptor (CAR) T-cell therapy that could potentially serve as a preparative regimen for acute myeloid leukemia (AML) patients undergoing allogeneic transplant.

The team created CAR T cells that target CD33 (CART33) and modified them with RNA so the cells would stop expressing CARs over time.

In mouse models of AML, the RNA-CART33 cells had an antileukemic effect and induced myeloablation.

The cells also stopped expressing CARs by the 2-week mark, which would allow for engraftment after allogeneic transplant, according to the researchers.

Saad S. Kenderian, MD, of the University of Pennsylvania in Philadelphia, presented this research at the 2015 BMT Tandem Meetings as one of the meeting’s “Best Abstracts” (abstract 1). The research was funded by Novartis.

“Allogeneic transplantation is the only potentially curative option in relapsed/refractory AML,” Dr Kenderian noted. “Outcomes are poor if patients are transplanted in residual disease  . . . , and these patients are often considered transplant-ineligible. Therefore, novel therapies are desperately needed.”

With this in mind, Dr Kenderian and his colleagues set out to develop a CAR T-cell therapy targeting CD33, which is expressed on AML blasts.

The researchers created a CAR from the anti-CD33 single-chain fragment variable of gemtuzumab ozogamicin, 41BB costimulation, CD3ζ signaling domain, and a lentiviral (LV) vector. They transduced T cells with this construct and expanded them in culture using anti-CD3/CD28 magnetic beads.

The team then tested these CART33 cells in NSGS mice engrafted with primary AML blasts. The mice received CART33 cells, another CAR T-cell therapy known as CART123, or control T cells.

At 4 weeks, mice that had received CART33 or CART123 cells were entirely leukemia-free, but the disease continued to progress in mice that received control T cells.

Likewise, when the experiment ended at 200 days, survival was 100% among mice that received CART33 or CART123, but all of the control mice had died. And at 200 days, CAR T cells were still circulating in the CART33- and CART123-treated mice.

Next, the researchers administered CART33 cells to HIS-NSG mice engrafted with human bone marrow and found the treatment resulted in myeloablation. There was a significant reduction of CD34-positive cells in mice that received CART33 compared to mice that received control T cells or no treatment.

“So based on our preclinical data, when we treat refractory AML with lentivirally transduced CART33, that will result in myeloablation, eradication of AML, and persistence of these CARs,” Dr Kenderian said.

“If allogeneic transplantation is performed at this aplastic stage, it will likely lead to rejection of the graft by persisting CAR therapy, which also means that elimination of CARs is necessary prior to stem cell infusion.”

So the researchers decided to create a transiently expressed, mRNA-modified CAR based on CART33. They electroporated T cells with this construct, and the cells expressed CARs for up to 6 days.

In experiments with the MOLM14 cell line, RNA-modified CART33 cells exhibited transient but comparable killing ability as LV-transduced CART33.

The researchers then tested RNA-CART33 in combination with chemotherapy in vivo. They transplanted NSG mice with MOLM14 and treated them with cyclophosphamide plus RNA-CART33 or cyclophosphamide plus control T cells.

Combination RNA-CART33 and chemotherapy prompted stronger, more durable antileukemic activity than cyclophosphamide and control T cells. Furthermore, there was a significant improvement in survival among RNA-CART33-treated mice (P=0.01).

Finally, Dr Kenderian and his colleagues tested the effect of RNA-CART33 on hematopoiesis. The team treated NSGS mice with busulfan and transplanted them with T-cell-depleted bone marrow. Following engraftment, mice received RNA-CART33 cells, LV-CART33 cells, or control T cells.

The researchers followed the mice for 2 weeks and found that both RNA-CART33 and LV-CART33 induced myeloablation. And at 14 days, LV-CART33-treated mice were still expressing CARs, but RNA-CART33-treated mice were not.

“Based on our preclinical data, if we treat refractory AML with RNA-modified CART33, that results in myeloablation, anti-AML activity, and biodegradable, non-persisting CARs,” Dr Kenderian summarized.

“If allogeneic transplantation follows at this stage, it will likely lead to engraftment. Therefore, we conclude from this study that RNA-CART33 could be incorporated in novel conditioning regimens and will be tested in pilot phase 1 studies.”

Micrograph showing MM

Patients with multiple myeloma (MM) appear to have better survival if they are first diagnosed with monoclonal gammopathy of undetermined significance (MGUS), according to a study published in JAMA Oncology.

The researchers think this may be because patients with MGUS are evaluated more often for signs of progression to MM. They may therefore be diagnosed with MM and started on therapy at an earlier stage than patients who have not been diagnosed with MGUS.

However, the study did not verify that MM patients initially diagnosed with MGUS were followed more closely than their peers.

So, as authors of a related editorial pointed out, it is difficult to confirm a causal relationship between closer follow-up and better prognosis.

Sigurdur Y. Kristinsson, MD, PhD, of the University of Iceland in Reykjavik, and his colleagues conducted this study, evaluating the impact of prior knowledge of MGUS diagnosis and coexisting illnesses on MM survival.

The study included all patients diagnosed with MM in Sweden (n=14,798) from 1976 to 2005. In all, 394 patients (2.7%) had previously been diagnosed with MGUS.

Patients with prior knowledge of MGUS had better overall survival than patients with MM who didn’t know when they had MGUS—a median survival of 2.8 years and 2.1 years, respectively (hazard ratio=0.86, P<0.01).

But patients with prior knowledge of their MGUS status had more coexisting illnesses, including systemic and organ-bound autoimmune diseases (P=0.02 for both), autoimmune diseases without auto-antibodies (P<0.001), infections (P<0.001), ischemic heart disease (P<0.001), heart failure (P=0.03), cerebrovascular diseases (P=0.04), and renal diseases (P<0.001).

Low M-protein concentration at MGUS diagnosis was associated with poorer survival among MM patients with prior knowledge of MGUS. Patients who had M-protein concentrations less than 0.5 g/dL had significantly worse survival than patients with concentrations of 0.5 to 3.0 g/dL (hazard ratio=1.86, P=0.01).

The researchers said the worse survival observed in these patients may be a result of less frequent clinical follow-up.

“Our results reflect the importance of lifelong follow-up for individuals diagnosed as having MGUS, independent of risk score, and highlight the need for better risk models based on the biology of the disease,” the researchers wrote.

“Patients should receive balanced information stressing not only the overall very low risk of progression to malignant neoplasm but also the symptoms that could signal such development and the need to consult their physician.”

Authors of a related editorial—Robert A. Kyle, MD, and S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota—expressed a somewhat different viewpoint.

“It cannot be determined whether MM patients with a known MGUS in the Icelandic study were followed more closely than those in whom a MGUS was not recognized, and, hence, it is difficult to attribute a causal relationship between follow-up and better prognosis,” they wrote.

“We also need studies to address the question of the possible merits of screening for the presence of MGUS in a normal, older population. The cost, inconvenience, and anxiety produced by the awareness of potential progression of a recognized MGUS, as well as the low absolute risk of progression (0.5% to 1%), probably override the possible potential benefit of screening for MGUS.”

Micrograph showing MM

Patients with multiple myeloma (MM) appear to have better survival if they are first diagnosed with monoclonal gammopathy of undetermined significance (MGUS), according to a study published in JAMA Oncology.

The researchers think this may be because patients with MGUS are evaluated more often for signs of progression to MM. They may therefore be diagnosed with MM and started on therapy at an earlier stage than patients who have not been diagnosed with MGUS.

However, the study did not verify that MM patients initially diagnosed with MGUS were followed more closely than their peers.

So, as authors of a related editorial pointed out, it is difficult to confirm a causal relationship between closer follow-up and better prognosis.

Sigurdur Y. Kristinsson, MD, PhD, of the University of Iceland in Reykjavik, and his colleagues conducted this study, evaluating the impact of prior knowledge of MGUS diagnosis and coexisting illnesses on MM survival.

The study included all patients diagnosed with MM in Sweden (n=14,798) from 1976 to 2005. In all, 394 patients (2.7%) had previously been diagnosed with MGUS.

Patients with prior knowledge of MGUS had better overall survival than patients with MM who didn’t know when they had MGUS—a median survival of 2.8 years and 2.1 years, respectively (hazard ratio=0.86, P<0.01).

But patients with prior knowledge of their MGUS status had more coexisting illnesses, including systemic and organ-bound autoimmune diseases (P=0.02 for both), autoimmune diseases without auto-antibodies (P<0.001), infections (P<0.001), ischemic heart disease (P<0.001), heart failure (P=0.03), cerebrovascular diseases (P=0.04), and renal diseases (P<0.001).

Low M-protein concentration at MGUS diagnosis was associated with poorer survival among MM patients with prior knowledge of MGUS. Patients who had M-protein concentrations less than 0.5 g/dL had significantly worse survival than patients with concentrations of 0.5 to 3.0 g/dL (hazard ratio=1.86, P=0.01).

The researchers said the worse survival observed in these patients may be a result of less frequent clinical follow-up.

“Our results reflect the importance of lifelong follow-up for individuals diagnosed as having MGUS, independent of risk score, and highlight the need for better risk models based on the biology of the disease,” the researchers wrote.

“Patients should receive balanced information stressing not only the overall very low risk of progression to malignant neoplasm but also the symptoms that could signal such development and the need to consult their physician.”

Authors of a related editorial—Robert A. Kyle, MD, and S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota—expressed a somewhat different viewpoint.

“It cannot be determined whether MM patients with a known MGUS in the Icelandic study were followed more closely than those in whom a MGUS was not recognized, and, hence, it is difficult to attribute a causal relationship between follow-up and better prognosis,” they wrote.

“We also need studies to address the question of the possible merits of screening for the presence of MGUS in a normal, older population. The cost, inconvenience, and anxiety produced by the awareness of potential progression of a recognized MGUS, as well as the low absolute risk of progression (0.5% to 1%), probably override the possible potential benefit of screening for MGUS.”

Micrograph showing MM

Patients with multiple myeloma (MM) appear to have better survival if they are first diagnosed with monoclonal gammopathy of undetermined significance (MGUS), according to a study published in JAMA Oncology.

The researchers think this may be because patients with MGUS are evaluated more often for signs of progression to MM. They may therefore be diagnosed with MM and started on therapy at an earlier stage than patients who have not been diagnosed with MGUS.

However, the study did not verify that MM patients initially diagnosed with MGUS were followed more closely than their peers.

So, as authors of a related editorial pointed out, it is difficult to confirm a causal relationship between closer follow-up and better prognosis.

Sigurdur Y. Kristinsson, MD, PhD, of the University of Iceland in Reykjavik, and his colleagues conducted this study, evaluating the impact of prior knowledge of MGUS diagnosis and coexisting illnesses on MM survival.

The study included all patients diagnosed with MM in Sweden (n=14,798) from 1976 to 2005. In all, 394 patients (2.7%) had previously been diagnosed with MGUS.

Patients with prior knowledge of MGUS had better overall survival than patients with MM who didn’t know when they had MGUS—a median survival of 2.8 years and 2.1 years, respectively (hazard ratio=0.86, P<0.01).

But patients with prior knowledge of their MGUS status had more coexisting illnesses, including systemic and organ-bound autoimmune diseases (P=0.02 for both), autoimmune diseases without auto-antibodies (P<0.001), infections (P<0.001), ischemic heart disease (P<0.001), heart failure (P=0.03), cerebrovascular diseases (P=0.04), and renal diseases (P<0.001).

Low M-protein concentration at MGUS diagnosis was associated with poorer survival among MM patients with prior knowledge of MGUS. Patients who had M-protein concentrations less than 0.5 g/dL had significantly worse survival than patients with concentrations of 0.5 to 3.0 g/dL (hazard ratio=1.86, P=0.01).

The researchers said the worse survival observed in these patients may be a result of less frequent clinical follow-up.

“Our results reflect the importance of lifelong follow-up for individuals diagnosed as having MGUS, independent of risk score, and highlight the need for better risk models based on the biology of the disease,” the researchers wrote.

“Patients should receive balanced information stressing not only the overall very low risk of progression to malignant neoplasm but also the symptoms that could signal such development and the need to consult their physician.”

Authors of a related editorial—Robert A. Kyle, MD, and S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota—expressed a somewhat different viewpoint.

“It cannot be determined whether MM patients with a known MGUS in the Icelandic study were followed more closely than those in whom a MGUS was not recognized, and, hence, it is difficult to attribute a causal relationship between follow-up and better prognosis,” they wrote.

“We also need studies to address the question of the possible merits of screening for the presence of MGUS in a normal, older population. The cost, inconvenience, and anxiety produced by the awareness of potential progression of a recognized MGUS, as well as the low absolute risk of progression (0.5% to 1%), probably override the possible potential benefit of screening for MGUS.”