Background: Patients with thyroid cancer often have distinctive characteristics that change as the cancer progresses to stage IV and warrants varied treatment. A Surveillance, Epidemiology, and End Results-based study reported that men with thyroid cancer of follicular cell origin are more likely to present with advanced disease compared with that of female patients. This is the largest study to evaluate stage IV thyroid cancer.

Methods: A population-based study was conducted using the National Cancer Database (NCDB), which captures nearly 70% of incident cancers in the U.S. For the accession years 2000 to 2012, NCDB took epidemiologic information for a sample of 343,386 thyroid cancer cases and used data from the 2012 U.S. census. The diagnosis of stage IV disease represented 6.88% (23,613) of the total patient population. The demographics of stage IV patients were compared with patients with all other stages using the chi-square test.

Results: There was an increased incidence of stage IV thyroid cancer in Medicare, lower high school graduation rates, annual median household income < $44,000, aged ≥ 70 years, male, more comorbidities, and further distance from a treatment facility (P < .0001). Ethnicity/race had little impact on the incidence of stage IV disease. Stage IV cancer incidence is higher in males (12.14%) compared with that of females (5.15%), and stage IV patients are more likely have Medicare (14.60%) or be uninsured (8.72%) than have private insurance (4.63%). Patients with ≥ 2 comorbidities (14.23%) are more than twice as likely to have stage IV as those without comorbidities (6.77%). Medullary and anaplastic cancers (20.08%) are much more likely to be stage IV than papillary (5.76%) or follicular cancers (3.94%, P < .0001).

Conclusions: Patients with the following characteristics are more likely to present with stage IV thyroid cancer: Medicare, less education, low income, older age, male, comorbidities, far from a treatment facility, and medullary or anaplastic thyroid cancer.

Background: Patients with thyroid cancer often have distinctive characteristics that change as the cancer progresses to stage IV and warrants varied treatment. A Surveillance, Epidemiology, and End Results-based study reported that men with thyroid cancer of follicular cell origin are more likely to present with advanced disease compared with that of female patients. This is the largest study to evaluate stage IV thyroid cancer.

Methods: A population-based study was conducted using the National Cancer Database (NCDB), which captures nearly 70% of incident cancers in the U.S. For the accession years 2000 to 2012, NCDB took epidemiologic information for a sample of 343,386 thyroid cancer cases and used data from the 2012 U.S. census. The diagnosis of stage IV disease represented 6.88% (23,613) of the total patient population. The demographics of stage IV patients were compared with patients with all other stages using the chi-square test.

Results: There was an increased incidence of stage IV thyroid cancer in Medicare, lower high school graduation rates, annual median household income < $44,000, aged ≥ 70 years, male, more comorbidities, and further distance from a treatment facility (P < .0001). Ethnicity/race had little impact on the incidence of stage IV disease. Stage IV cancer incidence is higher in males (12.14%) compared with that of females (5.15%), and stage IV patients are more likely have Medicare (14.60%) or be uninsured (8.72%) than have private insurance (4.63%). Patients with ≥ 2 comorbidities (14.23%) are more than twice as likely to have stage IV as those without comorbidities (6.77%). Medullary and anaplastic cancers (20.08%) are much more likely to be stage IV than papillary (5.76%) or follicular cancers (3.94%, P < .0001).

Conclusions: Patients with the following characteristics are more likely to present with stage IV thyroid cancer: Medicare, less education, low income, older age, male, comorbidities, far from a treatment facility, and medullary or anaplastic thyroid cancer.

Background: Patients with thyroid cancer often have distinctive characteristics that change as the cancer progresses to stage IV and warrants varied treatment. A Surveillance, Epidemiology, and End Results-based study reported that men with thyroid cancer of follicular cell origin are more likely to present with advanced disease compared with that of female patients. This is the largest study to evaluate stage IV thyroid cancer.

Methods: A population-based study was conducted using the National Cancer Database (NCDB), which captures nearly 70% of incident cancers in the U.S. For the accession years 2000 to 2012, NCDB took epidemiologic information for a sample of 343,386 thyroid cancer cases and used data from the 2012 U.S. census. The diagnosis of stage IV disease represented 6.88% (23,613) of the total patient population. The demographics of stage IV patients were compared with patients with all other stages using the chi-square test.

Results: There was an increased incidence of stage IV thyroid cancer in Medicare, lower high school graduation rates, annual median household income < $44,000, aged ≥ 70 years, male, more comorbidities, and further distance from a treatment facility (P < .0001). Ethnicity/race had little impact on the incidence of stage IV disease. Stage IV cancer incidence is higher in males (12.14%) compared with that of females (5.15%), and stage IV patients are more likely have Medicare (14.60%) or be uninsured (8.72%) than have private insurance (4.63%). Patients with ≥ 2 comorbidities (14.23%) are more than twice as likely to have stage IV as those without comorbidities (6.77%). Medullary and anaplastic cancers (20.08%) are much more likely to be stage IV than papillary (5.76%) or follicular cancers (3.94%, P < .0001).

Conclusions: Patients with the following characteristics are more likely to present with stage IV thyroid cancer: Medicare, less education, low income, older age, male, comorbidities, far from a treatment facility, and medullary or anaplastic thyroid cancer.

Neither psoriatic arthritis (PsA) nor cutaneous psoriasis (PsC) is an independent predictor of poor postoperative pain or function following a total hip arthroplasty, according to the results of a case-control study by Dr. Lisa A. Mandl and her colleagues.

The study’s participants underwent surgery between May 1, 2007, and Dec. 31, 2010, in a center that performs more than 4,300 THAs annually. All subjects lived for at least 2 years after their operations. The researchers compared pre- and postoperative data from patients in the following three categories: those with PsA, those with PsC without evidence of inflammatory arthritis, and those with osteoarthritis (OA). Patients with OA comprised the control group, which excluded any patient who self-reported a history of PsA, rheumatoid arthritis, lupus erythematosus, or any other systematic rheumatic disease, or who had documentation of skin psoriasis. The researchers acquired postoperative self-report data from 47 PsA patients, 106 PsC patients, and 864 OA patients. Seventeen percent of patients submitted information on their status at 1 year, 69% at 2 years, and 14% at 3-5 years.

The primary outcomes of interest were postoperative pain and function, which were assessed via the Hip Osteoarthritis Outcome Score (HOOS), from which the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was derived.

There were no statistically significant differences in postoperative WOMAC pain or function scores between the three groups of patients (P = .78 and .96, respectively). The mean pain scores were 14.9, 6.1, and 15.8 for patients with PsA, PsC, and OA, respectively. These patients’ mean function scores were 16.3, 19.6, and 18.8 for the PsA, PsC and OA groups, respectively.

Overall levels of satisfaction with the surgery were similar among the three groups (P = .54). Ninety-three percent of the PsA patients, 79% of the PsC patients, and 84% of the OA patients were “very satisfied” with their total hip arthroplasty. Between 1% and 3% of each group reported being “very dissatisfied” with their surgery. The researchers found that extent of skin disease was not associated with worse postoperative pain or function.

“Further work needs to be done to better understand the interplay of disease activity and quality of life on the outcomes of [total hip arthroplasty] in PsA and PsC,” they wrote.

Read the report in Arthritis & Rheumatology (doi: 10.1002/art.39431).

[email protected]

Neither psoriatic arthritis (PsA) nor cutaneous psoriasis (PsC) is an independent predictor of poor postoperative pain or function following a total hip arthroplasty, according to the results of a case-control study by Dr. Lisa A. Mandl and her colleagues.

The study’s participants underwent surgery between May 1, 2007, and Dec. 31, 2010, in a center that performs more than 4,300 THAs annually. All subjects lived for at least 2 years after their operations. The researchers compared pre- and postoperative data from patients in the following three categories: those with PsA, those with PsC without evidence of inflammatory arthritis, and those with osteoarthritis (OA). Patients with OA comprised the control group, which excluded any patient who self-reported a history of PsA, rheumatoid arthritis, lupus erythematosus, or any other systematic rheumatic disease, or who had documentation of skin psoriasis. The researchers acquired postoperative self-report data from 47 PsA patients, 106 PsC patients, and 864 OA patients. Seventeen percent of patients submitted information on their status at 1 year, 69% at 2 years, and 14% at 3-5 years.

The primary outcomes of interest were postoperative pain and function, which were assessed via the Hip Osteoarthritis Outcome Score (HOOS), from which the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was derived.

There were no statistically significant differences in postoperative WOMAC pain or function scores between the three groups of patients (P = .78 and .96, respectively). The mean pain scores were 14.9, 6.1, and 15.8 for patients with PsA, PsC, and OA, respectively. These patients’ mean function scores were 16.3, 19.6, and 18.8 for the PsA, PsC and OA groups, respectively.

Overall levels of satisfaction with the surgery were similar among the three groups (P = .54). Ninety-three percent of the PsA patients, 79% of the PsC patients, and 84% of the OA patients were “very satisfied” with their total hip arthroplasty. Between 1% and 3% of each group reported being “very dissatisfied” with their surgery. The researchers found that extent of skin disease was not associated with worse postoperative pain or function.

“Further work needs to be done to better understand the interplay of disease activity and quality of life on the outcomes of [total hip arthroplasty] in PsA and PsC,” they wrote.

Read the report in Arthritis & Rheumatology (doi: 10.1002/art.39431).

[email protected]

Neither psoriatic arthritis (PsA) nor cutaneous psoriasis (PsC) is an independent predictor of poor postoperative pain or function following a total hip arthroplasty, according to the results of a case-control study by Dr. Lisa A. Mandl and her colleagues.

The study’s participants underwent surgery between May 1, 2007, and Dec. 31, 2010, in a center that performs more than 4,300 THAs annually. All subjects lived for at least 2 years after their operations. The researchers compared pre- and postoperative data from patients in the following three categories: those with PsA, those with PsC without evidence of inflammatory arthritis, and those with osteoarthritis (OA). Patients with OA comprised the control group, which excluded any patient who self-reported a history of PsA, rheumatoid arthritis, lupus erythematosus, or any other systematic rheumatic disease, or who had documentation of skin psoriasis. The researchers acquired postoperative self-report data from 47 PsA patients, 106 PsC patients, and 864 OA patients. Seventeen percent of patients submitted information on their status at 1 year, 69% at 2 years, and 14% at 3-5 years.

The primary outcomes of interest were postoperative pain and function, which were assessed via the Hip Osteoarthritis Outcome Score (HOOS), from which the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was derived.

There were no statistically significant differences in postoperative WOMAC pain or function scores between the three groups of patients (P = .78 and .96, respectively). The mean pain scores were 14.9, 6.1, and 15.8 for patients with PsA, PsC, and OA, respectively. These patients’ mean function scores were 16.3, 19.6, and 18.8 for the PsA, PsC and OA groups, respectively.

Overall levels of satisfaction with the surgery were similar among the three groups (P = .54). Ninety-three percent of the PsA patients, 79% of the PsC patients, and 84% of the OA patients were “very satisfied” with their total hip arthroplasty. Between 1% and 3% of each group reported being “very dissatisfied” with their surgery. The researchers found that extent of skin disease was not associated with worse postoperative pain or function.

“Further work needs to be done to better understand the interplay of disease activity and quality of life on the outcomes of [total hip arthroplasty] in PsA and PsC,” they wrote.

Read the report in Arthritis & Rheumatology (doi: 10.1002/art.39431).

[email protected]

The prevalence of fibromyalgia in our clinical practices is about 2%-3%. But it may feel much higher, because some of these patients use a lot of staff and office time. Vacillations in our certainty about the diagnosis, inadequate time to differentiate new problems from the underlying one, failing to engage the patient in disease self-management, and inadequately exhausting the plethora of pharmacologic management options (however weak the data may be for each one) make care of patients with fibromyalgia challenging. Unfortunately, many of these patients are treated with chronic opioids.

So, maybe you have tried every pharmacologic option under the sun. But have you tried memantine?

Dr. Bárbara Olivan-Blázquez of the University of Zaragoza, Spain, and colleagues evaluated the efficacy of memantine for pain symptom control in fibromyalgia (Pain. 2014 Dec;155[12]:2517-25).

In this study, 63 patients with fibromyalgia were randomized to 20 mg/day of memantine or matching placebo for a total of 6 months, including an initial 1-month up-titration period. Follow-up occurred at 3 months and 6 months.

Compared with placebo, memantine decreased pain and depression at 3 months and 6 months. It also increased cognitive function and overall perceptions of function at 3 months and 6 months. More than 80% of patients completed the trial. Dizziness and headaches were the most commonly reported symptoms.

Why does it work? Memantine blocks glutamate, and glutamate may be a player in perpetuating the pain cycle for patients with fibromyalgia. Previously, memantine had been shown to be effective in other pain conditions such as complex regional pain syndrome and phantom limb pain. Memantine is well tolerated and is generically available. In my location, I was able to locate it for less than $1 per day of therapy.

So, before giving up hope or reaching for the opioid du jour, memantine may be worth a trial to decrease pain and improve function in our patients with fibromyalgia.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article. Follow him on Twitter @jonebbert.

The prevalence of fibromyalgia in our clinical practices is about 2%-3%. But it may feel much higher, because some of these patients use a lot of staff and office time. Vacillations in our certainty about the diagnosis, inadequate time to differentiate new problems from the underlying one, failing to engage the patient in disease self-management, and inadequately exhausting the plethora of pharmacologic management options (however weak the data may be for each one) make care of patients with fibromyalgia challenging. Unfortunately, many of these patients are treated with chronic opioids.

So, maybe you have tried every pharmacologic option under the sun. But have you tried memantine?

Dr. Bárbara Olivan-Blázquez of the University of Zaragoza, Spain, and colleagues evaluated the efficacy of memantine for pain symptom control in fibromyalgia (Pain. 2014 Dec;155[12]:2517-25).

In this study, 63 patients with fibromyalgia were randomized to 20 mg/day of memantine or matching placebo for a total of 6 months, including an initial 1-month up-titration period. Follow-up occurred at 3 months and 6 months.

Compared with placebo, memantine decreased pain and depression at 3 months and 6 months. It also increased cognitive function and overall perceptions of function at 3 months and 6 months. More than 80% of patients completed the trial. Dizziness and headaches were the most commonly reported symptoms.

Why does it work? Memantine blocks glutamate, and glutamate may be a player in perpetuating the pain cycle for patients with fibromyalgia. Previously, memantine had been shown to be effective in other pain conditions such as complex regional pain syndrome and phantom limb pain. Memantine is well tolerated and is generically available. In my location, I was able to locate it for less than $1 per day of therapy.

So, before giving up hope or reaching for the opioid du jour, memantine may be worth a trial to decrease pain and improve function in our patients with fibromyalgia.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article. Follow him on Twitter @jonebbert.

The prevalence of fibromyalgia in our clinical practices is about 2%-3%. But it may feel much higher, because some of these patients use a lot of staff and office time. Vacillations in our certainty about the diagnosis, inadequate time to differentiate new problems from the underlying one, failing to engage the patient in disease self-management, and inadequately exhausting the plethora of pharmacologic management options (however weak the data may be for each one) make care of patients with fibromyalgia challenging. Unfortunately, many of these patients are treated with chronic opioids.

So, maybe you have tried every pharmacologic option under the sun. But have you tried memantine?

Dr. Bárbara Olivan-Blázquez of the University of Zaragoza, Spain, and colleagues evaluated the efficacy of memantine for pain symptom control in fibromyalgia (Pain. 2014 Dec;155[12]:2517-25).

In this study, 63 patients with fibromyalgia were randomized to 20 mg/day of memantine or matching placebo for a total of 6 months, including an initial 1-month up-titration period. Follow-up occurred at 3 months and 6 months.

Compared with placebo, memantine decreased pain and depression at 3 months and 6 months. It also increased cognitive function and overall perceptions of function at 3 months and 6 months. More than 80% of patients completed the trial. Dizziness and headaches were the most commonly reported symptoms.

Why does it work? Memantine blocks glutamate, and glutamate may be a player in perpetuating the pain cycle for patients with fibromyalgia. Previously, memantine had been shown to be effective in other pain conditions such as complex regional pain syndrome and phantom limb pain. Memantine is well tolerated and is generically available. In my location, I was able to locate it for less than $1 per day of therapy.

So, before giving up hope or reaching for the opioid du jour, memantine may be worth a trial to decrease pain and improve function in our patients with fibromyalgia.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article. Follow him on Twitter @jonebbert.

Noninvasive cosmetic surgery procedures continue to increase in number, according to the American Society of Plastic Surgeons. Furthermore, these procedures are being performed in the offices of a growing number of physician specialties. As demand increases and offices become busy, there is increased delegation of these procedures to nurses, physician assistants, aestheticians, and medical assistants.

Austin et al (Dermatol Surg. 2015;41:827-832.) performed an Internet-based survey of physician members of the American Society for Dermatologic Surgery, the American Society for Laser Medicine and Surgery, and the American Society for Aesthetic Plastic Surgery to evaluate the delegation practices among the various specialties. The survey asked for physician training, age, gender, residency, and geographic location, as well as a breakdown of how much of their practice involved cosmetic procedures. Respondents were asked if they delegate procedures, to whom do they delegate (eg, registered nurse, physician assistant, MAs), and which procedures they delegate. A point system was used to give a score based on the perceived level of education and/or training of the person delegated to perform a procedure: do not delegate (1); physician assistant or nurse practitioner (2); registered nurse (3); and MA, aesthetician, or other (4).

Respondents included 823 physicians: 521 dermatologists and 302 nondermatologists. Of the respondents, 291 of dermatologists (55.9%) and 223 of nondermatologist physicians (73.8%) delegated cosmetic procedures. Procedures most often delegated by dermatologists compared to nondermatologists included chemical peels, neuromodulator and filler injections, laser hair removal, pulsed dye laser, tattoo removal, intense pulsed light, nonablative factional laser, and sclerotherapy.

The outcome of this survey shows that delegating certain cosmetic procedures is common, with more than half of all survey respondents delegating at least 1 cosmetic procedure. Dermatologists, as a whole, delegated less frequently than nondermatologist physicians, and when they did, dermatologists delegated to higher-level providers compared to nondermatologists. Medical practices in which the focus is primarily cosmetic and in those in which the physician is older also were more likely to delegate procedures.

What’s the issue?

There is tremendous variability between states about who is competent to perform many of the noninvasive cosmetic procedures. Some state medical boards specify the type of provider and the procedures allowed, while other states have no policy. However, this rule is changing, and there are more regulations being brought before the state medical boards with the goal of ensuring patient safety. As the demand for noninvasive procedures continues to grow, there will be an increase in the number of nonphysician providers performing these procedures. Patient safety should be at the forefront of all legislation, but at the same time there should be training courses and oversight boards to allow for safe delegation. Do you see yourself delegating more of these noninvasive procedures in the future?

We want to know your views! Tell us what you think.

Noninvasive cosmetic surgery procedures continue to increase in number, according to the American Society of Plastic Surgeons. Furthermore, these procedures are being performed in the offices of a growing number of physician specialties. As demand increases and offices become busy, there is increased delegation of these procedures to nurses, physician assistants, aestheticians, and medical assistants.

Austin et al (Dermatol Surg. 2015;41:827-832.) performed an Internet-based survey of physician members of the American Society for Dermatologic Surgery, the American Society for Laser Medicine and Surgery, and the American Society for Aesthetic Plastic Surgery to evaluate the delegation practices among the various specialties. The survey asked for physician training, age, gender, residency, and geographic location, as well as a breakdown of how much of their practice involved cosmetic procedures. Respondents were asked if they delegate procedures, to whom do they delegate (eg, registered nurse, physician assistant, MAs), and which procedures they delegate. A point system was used to give a score based on the perceived level of education and/or training of the person delegated to perform a procedure: do not delegate (1); physician assistant or nurse practitioner (2); registered nurse (3); and MA, aesthetician, or other (4).

Respondents included 823 physicians: 521 dermatologists and 302 nondermatologists. Of the respondents, 291 of dermatologists (55.9%) and 223 of nondermatologist physicians (73.8%) delegated cosmetic procedures. Procedures most often delegated by dermatologists compared to nondermatologists included chemical peels, neuromodulator and filler injections, laser hair removal, pulsed dye laser, tattoo removal, intense pulsed light, nonablative factional laser, and sclerotherapy.

The outcome of this survey shows that delegating certain cosmetic procedures is common, with more than half of all survey respondents delegating at least 1 cosmetic procedure. Dermatologists, as a whole, delegated less frequently than nondermatologist physicians, and when they did, dermatologists delegated to higher-level providers compared to nondermatologists. Medical practices in which the focus is primarily cosmetic and in those in which the physician is older also were more likely to delegate procedures.

What’s the issue?

There is tremendous variability between states about who is competent to perform many of the noninvasive cosmetic procedures. Some state medical boards specify the type of provider and the procedures allowed, while other states have no policy. However, this rule is changing, and there are more regulations being brought before the state medical boards with the goal of ensuring patient safety. As the demand for noninvasive procedures continues to grow, there will be an increase in the number of nonphysician providers performing these procedures. Patient safety should be at the forefront of all legislation, but at the same time there should be training courses and oversight boards to allow for safe delegation. Do you see yourself delegating more of these noninvasive procedures in the future?

We want to know your views! Tell us what you think.

Noninvasive cosmetic surgery procedures continue to increase in number, according to the American Society of Plastic Surgeons. Furthermore, these procedures are being performed in the offices of a growing number of physician specialties. As demand increases and offices become busy, there is increased delegation of these procedures to nurses, physician assistants, aestheticians, and medical assistants.

Austin et al (Dermatol Surg. 2015;41:827-832.) performed an Internet-based survey of physician members of the American Society for Dermatologic Surgery, the American Society for Laser Medicine and Surgery, and the American Society for Aesthetic Plastic Surgery to evaluate the delegation practices among the various specialties. The survey asked for physician training, age, gender, residency, and geographic location, as well as a breakdown of how much of their practice involved cosmetic procedures. Respondents were asked if they delegate procedures, to whom do they delegate (eg, registered nurse, physician assistant, MAs), and which procedures they delegate. A point system was used to give a score based on the perceived level of education and/or training of the person delegated to perform a procedure: do not delegate (1); physician assistant or nurse practitioner (2); registered nurse (3); and MA, aesthetician, or other (4).

Respondents included 823 physicians: 521 dermatologists and 302 nondermatologists. Of the respondents, 291 of dermatologists (55.9%) and 223 of nondermatologist physicians (73.8%) delegated cosmetic procedures. Procedures most often delegated by dermatologists compared to nondermatologists included chemical peels, neuromodulator and filler injections, laser hair removal, pulsed dye laser, tattoo removal, intense pulsed light, nonablative factional laser, and sclerotherapy.

The outcome of this survey shows that delegating certain cosmetic procedures is common, with more than half of all survey respondents delegating at least 1 cosmetic procedure. Dermatologists, as a whole, delegated less frequently than nondermatologist physicians, and when they did, dermatologists delegated to higher-level providers compared to nondermatologists. Medical practices in which the focus is primarily cosmetic and in those in which the physician is older also were more likely to delegate procedures.

What’s the issue?

There is tremendous variability between states about who is competent to perform many of the noninvasive cosmetic procedures. Some state medical boards specify the type of provider and the procedures allowed, while other states have no policy. However, this rule is changing, and there are more regulations being brought before the state medical boards with the goal of ensuring patient safety. As the demand for noninvasive procedures continues to grow, there will be an increase in the number of nonphysician providers performing these procedures. Patient safety should be at the forefront of all legislation, but at the same time there should be training courses and oversight boards to allow for safe delegation. Do you see yourself delegating more of these noninvasive procedures in the future?

We want to know your views! Tell us what you think.

Intermittent pneumatic compression remains the consensus choice as the sole prophylactic agent for deep vein thrombosis in low- or moderate-risk surgical patients, according to a literature analysis published online ahead of print in September in the Journal of Vascular Surgery: Venous and Lymphatic Disorders.

Dr. Nirvana Sadaghianloo of the University of Nice (France) Sophia Antipolis and Dr. Alan Dardik of Yale University in New Haven, Conn., used the MEDLINE and Cochrane libraries to find individual studies and meta-analyses published in English since 2011 assessing the efficacy of intermittent pneumatic compression (IPC) in preventing deep vein thrombosis (DVT), which included the American College of Chest Physicians ninth edition guidelines (2012). They stated that, although the overall quality of studies regarding the use of IPC was low, IPC showed efficacy in prevention of DVT for more than 30 years (J Vasc Surg Venous Lymphat Disord. 2015 doi: 10.1016/j.jvsv.2015.07.006).

©LeeAnnWhite/thinkstockphotos.com

“IPC represents a good alternative to pharmacologic agents when the risk of thrombosis is moderate or low or when the risk of bleeding is high or may have serious consequences for the patient,” they stated.

However, they also found that most recommendations suggested that, in high-risk patients, IPC plays a role primarily as an additional modality to provide additional benefit in preventing DVT when is used in combination with pharmacologic therapy. They highlighted how the choice of any thromboprophylactic agent required a systematic risk assessment as a critical prerequisite.

Overall, risk stratification was most frequently assessed by the Caprini or Rogers score for most general, abdominal-pelvic, bariatric, vascular, plastic, and gynecologic surgery patients and by the Padua Prediction Score for hospitalized medical patients. In addition, major orthopedic surgery patients and stroke patients with restricted mobility were usually considered high risk, Dr. Sadaghianloo and Dr. Dardik said.

From their assessment of the literature, they determined that “further studies are needed to assess practical clinical questions that remain unanswered, including optimal cuff length and location, sequence and duration of pressure, and whether use of IPC in an outpatient setting can be effective and achieve good compliance.”

The authors reported that they had no conflicts of interest.

[email protected]

Intermittent pneumatic compression remains the consensus choice as the sole prophylactic agent for deep vein thrombosis in low- or moderate-risk surgical patients, according to a literature analysis published online ahead of print in September in the Journal of Vascular Surgery: Venous and Lymphatic Disorders.

Dr. Nirvana Sadaghianloo of the University of Nice (France) Sophia Antipolis and Dr. Alan Dardik of Yale University in New Haven, Conn., used the MEDLINE and Cochrane libraries to find individual studies and meta-analyses published in English since 2011 assessing the efficacy of intermittent pneumatic compression (IPC) in preventing deep vein thrombosis (DVT), which included the American College of Chest Physicians ninth edition guidelines (2012). They stated that, although the overall quality of studies regarding the use of IPC was low, IPC showed efficacy in prevention of DVT for more than 30 years (J Vasc Surg Venous Lymphat Disord. 2015 doi: 10.1016/j.jvsv.2015.07.006).

©LeeAnnWhite/thinkstockphotos.com

“IPC represents a good alternative to pharmacologic agents when the risk of thrombosis is moderate or low or when the risk of bleeding is high or may have serious consequences for the patient,” they stated.

However, they also found that most recommendations suggested that, in high-risk patients, IPC plays a role primarily as an additional modality to provide additional benefit in preventing DVT when is used in combination with pharmacologic therapy. They highlighted how the choice of any thromboprophylactic agent required a systematic risk assessment as a critical prerequisite.

Overall, risk stratification was most frequently assessed by the Caprini or Rogers score for most general, abdominal-pelvic, bariatric, vascular, plastic, and gynecologic surgery patients and by the Padua Prediction Score for hospitalized medical patients. In addition, major orthopedic surgery patients and stroke patients with restricted mobility were usually considered high risk, Dr. Sadaghianloo and Dr. Dardik said.

From their assessment of the literature, they determined that “further studies are needed to assess practical clinical questions that remain unanswered, including optimal cuff length and location, sequence and duration of pressure, and whether use of IPC in an outpatient setting can be effective and achieve good compliance.”

The authors reported that they had no conflicts of interest.

[email protected]

Intermittent pneumatic compression remains the consensus choice as the sole prophylactic agent for deep vein thrombosis in low- or moderate-risk surgical patients, according to a literature analysis published online ahead of print in September in the Journal of Vascular Surgery: Venous and Lymphatic Disorders.

Dr. Nirvana Sadaghianloo of the University of Nice (France) Sophia Antipolis and Dr. Alan Dardik of Yale University in New Haven, Conn., used the MEDLINE and Cochrane libraries to find individual studies and meta-analyses published in English since 2011 assessing the efficacy of intermittent pneumatic compression (IPC) in preventing deep vein thrombosis (DVT), which included the American College of Chest Physicians ninth edition guidelines (2012). They stated that, although the overall quality of studies regarding the use of IPC was low, IPC showed efficacy in prevention of DVT for more than 30 years (J Vasc Surg Venous Lymphat Disord. 2015 doi: 10.1016/j.jvsv.2015.07.006).

©LeeAnnWhite/thinkstockphotos.com

“IPC represents a good alternative to pharmacologic agents when the risk of thrombosis is moderate or low or when the risk of bleeding is high or may have serious consequences for the patient,” they stated.

However, they also found that most recommendations suggested that, in high-risk patients, IPC plays a role primarily as an additional modality to provide additional benefit in preventing DVT when is used in combination with pharmacologic therapy. They highlighted how the choice of any thromboprophylactic agent required a systematic risk assessment as a critical prerequisite.

Overall, risk stratification was most frequently assessed by the Caprini or Rogers score for most general, abdominal-pelvic, bariatric, vascular, plastic, and gynecologic surgery patients and by the Padua Prediction Score for hospitalized medical patients. In addition, major orthopedic surgery patients and stroke patients with restricted mobility were usually considered high risk, Dr. Sadaghianloo and Dr. Dardik said.

From their assessment of the literature, they determined that “further studies are needed to assess practical clinical questions that remain unanswered, including optimal cuff length and location, sequence and duration of pressure, and whether use of IPC in an outpatient setting can be effective and achieve good compliance.”

The authors reported that they had no conflicts of interest.

[email protected]

The incidence of deep vein thrombosis (DVT) in knees undergoing routine assessment of damage was found to be low but suggests the need to interrogate the popliteal vein for evidence of thrombosis, according to Dr. Ryan M. Shulman of the joint department of medical imaging of University Health Network and Mount Sinai Hospital, Toronto, and his colleagues.

They documented the appearance and determined the prevalence of findings suspicious for popliteal vein thrombosis on magnetic resonance imaging (MRI) assessment of the knee joint by retrospectively reviewing 2,888 MRI examinations.

© Sebastian Kaulitzki/Thinkstock

MRI images were classified as showing either normal appearing popliteal vein or findings suspicious for popliteal vein thrombosis. They found 2,879 of the MRI studies as having a normal appearing popliteal vein, with 9 showing findings suspicious for popliteal vein thrombosis.

“Although the prevalence of MR findings is low (0.3%), our findings reiterate the need to interrogate the popliteal vein for evidence of thrombosis,” Dr. Shulman and his colleagues concluded.

Find the full study online the Journal of Clinical Imaging 2015 (doi: 10.1016/j.clinimag.2015.09.008).

[email protected]

The incidence of deep vein thrombosis (DVT) in knees undergoing routine assessment of damage was found to be low but suggests the need to interrogate the popliteal vein for evidence of thrombosis, according to Dr. Ryan M. Shulman of the joint department of medical imaging of University Health Network and Mount Sinai Hospital, Toronto, and his colleagues.

They documented the appearance and determined the prevalence of findings suspicious for popliteal vein thrombosis on magnetic resonance imaging (MRI) assessment of the knee joint by retrospectively reviewing 2,888 MRI examinations.

© Sebastian Kaulitzki/Thinkstock

MRI images were classified as showing either normal appearing popliteal vein or findings suspicious for popliteal vein thrombosis. They found 2,879 of the MRI studies as having a normal appearing popliteal vein, with 9 showing findings suspicious for popliteal vein thrombosis.

“Although the prevalence of MR findings is low (0.3%), our findings reiterate the need to interrogate the popliteal vein for evidence of thrombosis,” Dr. Shulman and his colleagues concluded.

Find the full study online the Journal of Clinical Imaging 2015 (doi: 10.1016/j.clinimag.2015.09.008).

[email protected]

The incidence of deep vein thrombosis (DVT) in knees undergoing routine assessment of damage was found to be low but suggests the need to interrogate the popliteal vein for evidence of thrombosis, according to Dr. Ryan M. Shulman of the joint department of medical imaging of University Health Network and Mount Sinai Hospital, Toronto, and his colleagues.

They documented the appearance and determined the prevalence of findings suspicious for popliteal vein thrombosis on magnetic resonance imaging (MRI) assessment of the knee joint by retrospectively reviewing 2,888 MRI examinations.

© Sebastian Kaulitzki/Thinkstock

MRI images were classified as showing either normal appearing popliteal vein or findings suspicious for popliteal vein thrombosis. They found 2,879 of the MRI studies as having a normal appearing popliteal vein, with 9 showing findings suspicious for popliteal vein thrombosis.

“Although the prevalence of MR findings is low (0.3%), our findings reiterate the need to interrogate the popliteal vein for evidence of thrombosis,” Dr. Shulman and his colleagues concluded.

Find the full study online the Journal of Clinical Imaging 2015 (doi: 10.1016/j.clinimag.2015.09.008).

[email protected]

NEW YORK – “Inject locally, treat globally” may become a new mantra for cancer immunotherapy. Dr. Ronald Levy, professor and chief of the department of oncology at Stanford (Calif.) University, discussed impressive and durable systemic results from local treatment of tumors, reviewing his group’s recent work and discussing ongoing early stage clinical trials.

In the hope of triggering an immune response that induces a systemic CD8 T-cell response, Dr. Levy and other investigators began experimenting with intralesional injections of immunotherapies, with and without adjunctive radiation or chemotherapy. The principle has been evaluated in a mouse model, in which up to 80% of mice receiving intratumoral immunotherapy were cured. Now, human trials are underway for solid tumors as well as lymphoma.

An early clinical trial involving 15 patients with recurrent low-grade B-cell lymphoma combined targeted low-dose radiation of a single tumor site with injection of CpG, immune-boosting snippets of DNA, into the same site. Looking for partial or complete regression, investigators saw promising results, though some patients who were responders didn’t see full effect until 24 weeks after injection (J Clin Oncol. 2010 Oct 1;28[28]:4324-32). The overall objective response rate was 27%, although 80% of patients (12 of 15) had stable disease or partial or complete response through a median follow-up of 33.7 months. Some individual patients had marked regression or disappearance of bulky tumors at distant sites.

CpG – motifs of cytosines and guanines – were strung together, said Dr. Levy, with a sulfur rather than a phosphate backbone to make them more stable for injection. These bits of DNA, which are present in both bacteria and vertebrates, are an agonist for toll-like receptor 9, activating B cells and dendritic cells, and then tumor-specific T-cells.

Dr. Levy and his collaborators used a two-tumor mouse model to track intralesional injection effectiveness for a variety of immunotherapies. Mice seeded with tumor cells bilaterally over the abdomen were injected with CpG and two other immune therapies at a single abdominal tumor site, and bilateral regression, if any, was tracked in comparison to systemic immunotherapy (J Clin Invest. 2013;123[6]:2447-63).

Though both treatment arms had good initial response, 70% of the systemically treated mice relapsed by 150 days after injection, compared with just 10% of those receiving intratumoral therapy (P = .002).

Of the 23 mice whose therapy consisted of intratumoral administration of CpG together with anti-CTLA4 and anti-OX40 antibodies (aCTLA4 and aOX40), 21 (91%) were alive 50 days after treatment. These mice fared better than did those receiving any other intratumoral treatment combination (P = .004, compared with CpG+aOX40; P = .03, compared with aCTLA4), suggesting a synergistic benefit to the triple combination.

Somewhat surprisingly, even murine models that also had tumor seeding into brain tissue saw marked reduction or even resolution of brain tumors, showing that the blood-brain barrier does not impede the effect within the CNS.

What didn’t work? PD-1 inhibitors were not particularly effective at provoking a systemic effect when injected into tumors. Peritumoral injection, though theoretically taking advantage of some aspects of the tumor microenvironment, also did not show global effect.

Based on the human CpG + radiation trials and the mouse experiments, the research group is proceeding with phase I and II clinical trials of CpG in combinations with aCTLA4 and aOX40. These, Dr. Levy said, were more likely to be available clinically, and human intratumoral T regulatory cells are known to express both CTLA4 and OX40.

All agents and combinations had an enhancing effect, said Dr. Levy. “We like this treatment and trial design,” he said, noting that everyone sees benefit at the local injection site, and some see global results.

Dr. Levy discussed multiple studies, and he disclosed receiving grant support from Pfizer, Dynavax, and Bristol-Myers Squibb. He also has served as a consultant to Five Prime, Kite, BeiGene, Innate Pharma, Bullet Biotech, and Immune Design.

[email protected]

NEW YORK – “Inject locally, treat globally” may become a new mantra for cancer immunotherapy. Dr. Ronald Levy, professor and chief of the department of oncology at Stanford (Calif.) University, discussed impressive and durable systemic results from local treatment of tumors, reviewing his group’s recent work and discussing ongoing early stage clinical trials.

In the hope of triggering an immune response that induces a systemic CD8 T-cell response, Dr. Levy and other investigators began experimenting with intralesional injections of immunotherapies, with and without adjunctive radiation or chemotherapy. The principle has been evaluated in a mouse model, in which up to 80% of mice receiving intratumoral immunotherapy were cured. Now, human trials are underway for solid tumors as well as lymphoma.

An early clinical trial involving 15 patients with recurrent low-grade B-cell lymphoma combined targeted low-dose radiation of a single tumor site with injection of CpG, immune-boosting snippets of DNA, into the same site. Looking for partial or complete regression, investigators saw promising results, though some patients who were responders didn’t see full effect until 24 weeks after injection (J Clin Oncol. 2010 Oct 1;28[28]:4324-32). The overall objective response rate was 27%, although 80% of patients (12 of 15) had stable disease or partial or complete response through a median follow-up of 33.7 months. Some individual patients had marked regression or disappearance of bulky tumors at distant sites.

CpG – motifs of cytosines and guanines – were strung together, said Dr. Levy, with a sulfur rather than a phosphate backbone to make them more stable for injection. These bits of DNA, which are present in both bacteria and vertebrates, are an agonist for toll-like receptor 9, activating B cells and dendritic cells, and then tumor-specific T-cells.

Dr. Levy and his collaborators used a two-tumor mouse model to track intralesional injection effectiveness for a variety of immunotherapies. Mice seeded with tumor cells bilaterally over the abdomen were injected with CpG and two other immune therapies at a single abdominal tumor site, and bilateral regression, if any, was tracked in comparison to systemic immunotherapy (J Clin Invest. 2013;123[6]:2447-63).

Though both treatment arms had good initial response, 70% of the systemically treated mice relapsed by 150 days after injection, compared with just 10% of those receiving intratumoral therapy (P = .002).

Of the 23 mice whose therapy consisted of intratumoral administration of CpG together with anti-CTLA4 and anti-OX40 antibodies (aCTLA4 and aOX40), 21 (91%) were alive 50 days after treatment. These mice fared better than did those receiving any other intratumoral treatment combination (P = .004, compared with CpG+aOX40; P = .03, compared with aCTLA4), suggesting a synergistic benefit to the triple combination.

Somewhat surprisingly, even murine models that also had tumor seeding into brain tissue saw marked reduction or even resolution of brain tumors, showing that the blood-brain barrier does not impede the effect within the CNS.

What didn’t work? PD-1 inhibitors were not particularly effective at provoking a systemic effect when injected into tumors. Peritumoral injection, though theoretically taking advantage of some aspects of the tumor microenvironment, also did not show global effect.

Based on the human CpG + radiation trials and the mouse experiments, the research group is proceeding with phase I and II clinical trials of CpG in combinations with aCTLA4 and aOX40. These, Dr. Levy said, were more likely to be available clinically, and human intratumoral T regulatory cells are known to express both CTLA4 and OX40.

All agents and combinations had an enhancing effect, said Dr. Levy. “We like this treatment and trial design,” he said, noting that everyone sees benefit at the local injection site, and some see global results.

Dr. Levy discussed multiple studies, and he disclosed receiving grant support from Pfizer, Dynavax, and Bristol-Myers Squibb. He also has served as a consultant to Five Prime, Kite, BeiGene, Innate Pharma, Bullet Biotech, and Immune Design.

[email protected]

NEW YORK – “Inject locally, treat globally” may become a new mantra for cancer immunotherapy. Dr. Ronald Levy, professor and chief of the department of oncology at Stanford (Calif.) University, discussed impressive and durable systemic results from local treatment of tumors, reviewing his group’s recent work and discussing ongoing early stage clinical trials.

In the hope of triggering an immune response that induces a systemic CD8 T-cell response, Dr. Levy and other investigators began experimenting with intralesional injections of immunotherapies, with and without adjunctive radiation or chemotherapy. The principle has been evaluated in a mouse model, in which up to 80% of mice receiving intratumoral immunotherapy were cured. Now, human trials are underway for solid tumors as well as lymphoma.

An early clinical trial involving 15 patients with recurrent low-grade B-cell lymphoma combined targeted low-dose radiation of a single tumor site with injection of CpG, immune-boosting snippets of DNA, into the same site. Looking for partial or complete regression, investigators saw promising results, though some patients who were responders didn’t see full effect until 24 weeks after injection (J Clin Oncol. 2010 Oct 1;28[28]:4324-32). The overall objective response rate was 27%, although 80% of patients (12 of 15) had stable disease or partial or complete response through a median follow-up of 33.7 months. Some individual patients had marked regression or disappearance of bulky tumors at distant sites.

CpG – motifs of cytosines and guanines – were strung together, said Dr. Levy, with a sulfur rather than a phosphate backbone to make them more stable for injection. These bits of DNA, which are present in both bacteria and vertebrates, are an agonist for toll-like receptor 9, activating B cells and dendritic cells, and then tumor-specific T-cells.

Dr. Levy and his collaborators used a two-tumor mouse model to track intralesional injection effectiveness for a variety of immunotherapies. Mice seeded with tumor cells bilaterally over the abdomen were injected with CpG and two other immune therapies at a single abdominal tumor site, and bilateral regression, if any, was tracked in comparison to systemic immunotherapy (J Clin Invest. 2013;123[6]:2447-63).

Though both treatment arms had good initial response, 70% of the systemically treated mice relapsed by 150 days after injection, compared with just 10% of those receiving intratumoral therapy (P = .002).

Of the 23 mice whose therapy consisted of intratumoral administration of CpG together with anti-CTLA4 and anti-OX40 antibodies (aCTLA4 and aOX40), 21 (91%) were alive 50 days after treatment. These mice fared better than did those receiving any other intratumoral treatment combination (P = .004, compared with CpG+aOX40; P = .03, compared with aCTLA4), suggesting a synergistic benefit to the triple combination.

Somewhat surprisingly, even murine models that also had tumor seeding into brain tissue saw marked reduction or even resolution of brain tumors, showing that the blood-brain barrier does not impede the effect within the CNS.

What didn’t work? PD-1 inhibitors were not particularly effective at provoking a systemic effect when injected into tumors. Peritumoral injection, though theoretically taking advantage of some aspects of the tumor microenvironment, also did not show global effect.

Based on the human CpG + radiation trials and the mouse experiments, the research group is proceeding with phase I and II clinical trials of CpG in combinations with aCTLA4 and aOX40. These, Dr. Levy said, were more likely to be available clinically, and human intratumoral T regulatory cells are known to express both CTLA4 and OX40.

All agents and combinations had an enhancing effect, said Dr. Levy. “We like this treatment and trial design,” he said, noting that everyone sees benefit at the local injection site, and some see global results.

Dr. Levy discussed multiple studies, and he disclosed receiving grant support from Pfizer, Dynavax, and Bristol-Myers Squibb. He also has served as a consultant to Five Prime, Kite, BeiGene, Innate Pharma, Bullet Biotech, and Immune Design.

[email protected]

Patient receiving chemotherapy

Photo by Rhoda Baer

SAN DIEGO—Monitoring the microbiome during chemotherapy might help reduce infections in leukemia patients, according to research presented at ICAAC/ICC 2015.

The researchers studied buccal and fecal samples from patients with acute myeloid leukemia (AML) who were undergoing induction chemotherapy.

This revealed that decreased microbial diversity was associated with an increased risk of infection.

Jessica Galloway-Peña, PhD, of The University of Texas MD Anderson Cancer Center in Houston, and her colleagues described this work in a poster presentation at the meeting (poster B-993).

The team analyzed samples from 34 AML patients. All of the patients received prophylactic antimicrobials, and 91% received systemic antibiotics. The patients received an average of 5.4 different antibiotics for an average duration of 6.5 days.

The researchers collected buccal and fecal specimens from the patients every 96 hours over the course of induction chemotherapy. This yielded 276 buccal and 202 fecal samples—an average of 8 oral and 6 stool samples per patient.

The team used 16S rRNA V4 region sequencing to assign bacterial taxa and calculate α- and β-diversities. They had a total of 16,082,550 high-quality reads.

Analyzing these data, the researchers found that decreased microbial diversity, both at baseline and throughout induction, was associated with an increased risk of infection.

“We found the baseline microbial diversities from stool samples were significantly lower in patients that developed infections during chemotherapy compared to those that did not [P=0.006],” Dr Galloway-Peña said.

She and her colleagues also found that, overall, there was a significant decrease in oral (P=0.006) and intestinal (P<0.001) microbial diversity over the course of chemotherapy, although not all patients experienced decreases. There was a linear correlation between oral and stool microbiome changes (P=0.004).

In addition, over the course of induction, there was a significant increase (P=0.02) in the rates of bacterial domination (>30% of the microbiome dominated by 1 organism) by common causes of bacteremia, such as Streptococcus, Bacteriodes, Rothia, and Staphylococcus.

However, if patients were able to maintain a healthy microbiome overall or if they experienced an increase in microbial diversity over the induction course, they remained infection-free in the 90 days after induction.

Dr Galloway-Peña and her colleagues also assessed the role common antibiotics play in microbial diversity. And they found that carbapenems significantly decreased diversity.

There was a significant difference in oral and stool diversity when patients received carbapenems for at least 72 hours and when they did not (P=0.03). But there was no significant difference for piperacillin-tazobactam (P=1.0) or cefepime (P=0.48).

“This study shows that, in the future, doctors could use microbiome sampling in order to predict the chance of infectious complications during chemotherapy and that monitoring of a patient’s microbiome during induction chemotherapy could also predict their risk for microbial-related illness during subsequent treatments,” Dr Galloway-Peña said.

In addition, monitoring the microbiome could potentially mitigate the overuse of antimicrobials by allowing physicians to stratify patients according to their risk of developing an infection.

Patient receiving chemotherapy

Photo by Rhoda Baer

SAN DIEGO—Monitoring the microbiome during chemotherapy might help reduce infections in leukemia patients, according to research presented at ICAAC/ICC 2015.

The researchers studied buccal and fecal samples from patients with acute myeloid leukemia (AML) who were undergoing induction chemotherapy.

This revealed that decreased microbial diversity was associated with an increased risk of infection.

Jessica Galloway-Peña, PhD, of The University of Texas MD Anderson Cancer Center in Houston, and her colleagues described this work in a poster presentation at the meeting (poster B-993).

The team analyzed samples from 34 AML patients. All of the patients received prophylactic antimicrobials, and 91% received systemic antibiotics. The patients received an average of 5.4 different antibiotics for an average duration of 6.5 days.

The researchers collected buccal and fecal specimens from the patients every 96 hours over the course of induction chemotherapy. This yielded 276 buccal and 202 fecal samples—an average of 8 oral and 6 stool samples per patient.

The team used 16S rRNA V4 region sequencing to assign bacterial taxa and calculate α- and β-diversities. They had a total of 16,082,550 high-quality reads.

Analyzing these data, the researchers found that decreased microbial diversity, both at baseline and throughout induction, was associated with an increased risk of infection.

“We found the baseline microbial diversities from stool samples were significantly lower in patients that developed infections during chemotherapy compared to those that did not [P=0.006],” Dr Galloway-Peña said.

She and her colleagues also found that, overall, there was a significant decrease in oral (P=0.006) and intestinal (P<0.001) microbial diversity over the course of chemotherapy, although not all patients experienced decreases. There was a linear correlation between oral and stool microbiome changes (P=0.004).

In addition, over the course of induction, there was a significant increase (P=0.02) in the rates of bacterial domination (>30% of the microbiome dominated by 1 organism) by common causes of bacteremia, such as Streptococcus, Bacteriodes, Rothia, and Staphylococcus.

However, if patients were able to maintain a healthy microbiome overall or if they experienced an increase in microbial diversity over the induction course, they remained infection-free in the 90 days after induction.

Dr Galloway-Peña and her colleagues also assessed the role common antibiotics play in microbial diversity. And they found that carbapenems significantly decreased diversity.

There was a significant difference in oral and stool diversity when patients received carbapenems for at least 72 hours and when they did not (P=0.03). But there was no significant difference for piperacillin-tazobactam (P=1.0) or cefepime (P=0.48).

“This study shows that, in the future, doctors could use microbiome sampling in order to predict the chance of infectious complications during chemotherapy and that monitoring of a patient’s microbiome during induction chemotherapy could also predict their risk for microbial-related illness during subsequent treatments,” Dr Galloway-Peña said.

In addition, monitoring the microbiome could potentially mitigate the overuse of antimicrobials by allowing physicians to stratify patients according to their risk of developing an infection.

Patient receiving chemotherapy

Photo by Rhoda Baer

SAN DIEGO—Monitoring the microbiome during chemotherapy might help reduce infections in leukemia patients, according to research presented at ICAAC/ICC 2015.

The researchers studied buccal and fecal samples from patients with acute myeloid leukemia (AML) who were undergoing induction chemotherapy.

This revealed that decreased microbial diversity was associated with an increased risk of infection.

Jessica Galloway-Peña, PhD, of The University of Texas MD Anderson Cancer Center in Houston, and her colleagues described this work in a poster presentation at the meeting (poster B-993).

The team analyzed samples from 34 AML patients. All of the patients received prophylactic antimicrobials, and 91% received systemic antibiotics. The patients received an average of 5.4 different antibiotics for an average duration of 6.5 days.

The researchers collected buccal and fecal specimens from the patients every 96 hours over the course of induction chemotherapy. This yielded 276 buccal and 202 fecal samples—an average of 8 oral and 6 stool samples per patient.

The team used 16S rRNA V4 region sequencing to assign bacterial taxa and calculate α- and β-diversities. They had a total of 16,082,550 high-quality reads.

Analyzing these data, the researchers found that decreased microbial diversity, both at baseline and throughout induction, was associated with an increased risk of infection.

“We found the baseline microbial diversities from stool samples were significantly lower in patients that developed infections during chemotherapy compared to those that did not [P=0.006],” Dr Galloway-Peña said.

She and her colleagues also found that, overall, there was a significant decrease in oral (P=0.006) and intestinal (P<0.001) microbial diversity over the course of chemotherapy, although not all patients experienced decreases. There was a linear correlation between oral and stool microbiome changes (P=0.004).

In addition, over the course of induction, there was a significant increase (P=0.02) in the rates of bacterial domination (>30% of the microbiome dominated by 1 organism) by common causes of bacteremia, such as Streptococcus, Bacteriodes, Rothia, and Staphylococcus.

However, if patients were able to maintain a healthy microbiome overall or if they experienced an increase in microbial diversity over the induction course, they remained infection-free in the 90 days after induction.

Dr Galloway-Peña and her colleagues also assessed the role common antibiotics play in microbial diversity. And they found that carbapenems significantly decreased diversity.

There was a significant difference in oral and stool diversity when patients received carbapenems for at least 72 hours and when they did not (P=0.03). But there was no significant difference for piperacillin-tazobactam (P=1.0) or cefepime (P=0.48).

“This study shows that, in the future, doctors could use microbiome sampling in order to predict the chance of infectious complications during chemotherapy and that monitoring of a patient’s microbiome during induction chemotherapy could also predict their risk for microbial-related illness during subsequent treatments,” Dr Galloway-Peña said.

In addition, monitoring the microbiome could potentially mitigate the overuse of antimicrobials by allowing physicians to stratify patients according to their risk of developing an infection.

Carl June, MD

Photo courtesy of the

University of Pennsylvania

NEW YORK—The 5-year follow-up of the phase 1 trial of CTL019 in relapsed or refractory chronic lymphoblastic leukemia (CLL) is allowing investigators to define more clearly who will respond to chimeric antigen receptor (CAR) T cells directed against CD19.

One thing investigators have determined is that persistence of the CARs is essential for long-term responses.

In the first 2 patients who achieved a complete remission (CR), CAR T cells persisted for more than 4 years. In addition, no patient in CR has relapsed to date.

Of the 14 patients enrolled in the trial, 4 (28%) achieved a CR, 4 (28%) achieved a partial response, and 6 (43%) had no response, for an overall response rate of 57%.

These results were recently published in Science Translational Medicine.

Carl June, MD, of the University of Pennsylvania in Philadelphia, shared some insights into the research with attendees at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

Dr June explained that CTL019 is a CD19-directed single chain variable fragment with a 4-1BB signaling module that transduces T cells with a lentiviral vector. The technology was developed at the University of Pennsylvania and subsequently licensed to Novartis.

In the phase 1 trial of CTL019 in CLL, patients who achieved complete remission have very high levels of CARs—100% of the circulating T cells—but the non-responders don’t. The CARs engrafted in non-responders but did not proliferate.

“So the biomarker correlate of success is persistence and proliferation, in CLL at least,” Dr June said.

The investigators performed IGH next-generation sequencing and found no detectable CLL clones in the complete responders, including 1 patient at 3.5 years and another at 4 years post-infusion.

“There was no clinically evident disease in these patients,” Dr June said, “and so the responses are durable.”

The team also believes that at least a subset of the cells remains functional because the patients still had B-cell aplasia.

The investigators have not observed a CD19 loss in any CLL patient who responded.

“Patients who have gone into remission stay in remission,” Dr June added.

Kinetics of delayed CR

Dr June discussed in detail Patient 10, whose response was somewhat different from the other complete responders. Patient 10 achieved a CR, but the response was delayed. It took 51 days after infusion, compared to about 10 days in the other complete responders.

Patient 10 was initially scored as a failure at the 28-day evaluation. Eventually, he had marked improvement, and, by a year, he was in CR.

He required hospitalization for tumor lysis syndrome and treatment with tocilizumab for cytokine release syndrome.

Patient 10 had a single cell that investigators surmise could have been responsible for the tumor elimination.

“In fact, on day 28, when he still had tumor, his CARs were polyclonal,” Dr June said. “So we stained and isolated his CARs by sorting, and, at time of tumor elimination, he had descendants of 1 CAR.”

Nevertheless, Patient 10’s response is durable. He is now 81 years old and remains engrafted with CAR19 cells.

Investigators hypothesize that the kinetics and CAR proliferation were so different in Patient 10 because Tet2 was disrupted by the integration of the CAR into the intronic region.

“What we don’t know is whether Tet2 was a passenger or a driver here,” Dr June observed. “Did it actually aid the function of the CAR cells or was it just a marker?”

He noted that Tet2 has been shown in acute myeloid leukemia to increase stem cell renewal, “and it may well have done that in this patient.”

Carl June, MD

Photo courtesy of the

University of Pennsylvania

NEW YORK—The 5-year follow-up of the phase 1 trial of CTL019 in relapsed or refractory chronic lymphoblastic leukemia (CLL) is allowing investigators to define more clearly who will respond to chimeric antigen receptor (CAR) T cells directed against CD19.

One thing investigators have determined is that persistence of the CARs is essential for long-term responses.

In the first 2 patients who achieved a complete remission (CR), CAR T cells persisted for more than 4 years. In addition, no patient in CR has relapsed to date.

Of the 14 patients enrolled in the trial, 4 (28%) achieved a CR, 4 (28%) achieved a partial response, and 6 (43%) had no response, for an overall response rate of 57%.

These results were recently published in Science Translational Medicine.

Carl June, MD, of the University of Pennsylvania in Philadelphia, shared some insights into the research with attendees at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

Dr June explained that CTL019 is a CD19-directed single chain variable fragment with a 4-1BB signaling module that transduces T cells with a lentiviral vector. The technology was developed at the University of Pennsylvania and subsequently licensed to Novartis.

In the phase 1 trial of CTL019 in CLL, patients who achieved complete remission have very high levels of CARs—100% of the circulating T cells—but the non-responders don’t. The CARs engrafted in non-responders but did not proliferate.

“So the biomarker correlate of success is persistence and proliferation, in CLL at least,” Dr June said.

The investigators performed IGH next-generation sequencing and found no detectable CLL clones in the complete responders, including 1 patient at 3.5 years and another at 4 years post-infusion.

“There was no clinically evident disease in these patients,” Dr June said, “and so the responses are durable.”

The team also believes that at least a subset of the cells remains functional because the patients still had B-cell aplasia.

The investigators have not observed a CD19 loss in any CLL patient who responded.

“Patients who have gone into remission stay in remission,” Dr June added.

Kinetics of delayed CR

Dr June discussed in detail Patient 10, whose response was somewhat different from the other complete responders. Patient 10 achieved a CR, but the response was delayed. It took 51 days after infusion, compared to about 10 days in the other complete responders.

Patient 10 was initially scored as a failure at the 28-day evaluation. Eventually, he had marked improvement, and, by a year, he was in CR.

He required hospitalization for tumor lysis syndrome and treatment with tocilizumab for cytokine release syndrome.

Patient 10 had a single cell that investigators surmise could have been responsible for the tumor elimination.

“In fact, on day 28, when he still had tumor, his CARs were polyclonal,” Dr June said. “So we stained and isolated his CARs by sorting, and, at time of tumor elimination, he had descendants of 1 CAR.”

Nevertheless, Patient 10’s response is durable. He is now 81 years old and remains engrafted with CAR19 cells.

Investigators hypothesize that the kinetics and CAR proliferation were so different in Patient 10 because Tet2 was disrupted by the integration of the CAR into the intronic region.

“What we don’t know is whether Tet2 was a passenger or a driver here,” Dr June observed. “Did it actually aid the function of the CAR cells or was it just a marker?”

He noted that Tet2 has been shown in acute myeloid leukemia to increase stem cell renewal, “and it may well have done that in this patient.”

Carl June, MD

Photo courtesy of the

University of Pennsylvania

NEW YORK—The 5-year follow-up of the phase 1 trial of CTL019 in relapsed or refractory chronic lymphoblastic leukemia (CLL) is allowing investigators to define more clearly who will respond to chimeric antigen receptor (CAR) T cells directed against CD19.

One thing investigators have determined is that persistence of the CARs is essential for long-term responses.

In the first 2 patients who achieved a complete remission (CR), CAR T cells persisted for more than 4 years. In addition, no patient in CR has relapsed to date.

Of the 14 patients enrolled in the trial, 4 (28%) achieved a CR, 4 (28%) achieved a partial response, and 6 (43%) had no response, for an overall response rate of 57%.

These results were recently published in Science Translational Medicine.

Carl June, MD, of the University of Pennsylvania in Philadelphia, shared some insights into the research with attendees at the inaugural CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference.

Dr June explained that CTL019 is a CD19-directed single chain variable fragment with a 4-1BB signaling module that transduces T cells with a lentiviral vector. The technology was developed at the University of Pennsylvania and subsequently licensed to Novartis.

In the phase 1 trial of CTL019 in CLL, patients who achieved complete remission have very high levels of CARs—100% of the circulating T cells—but the non-responders don’t. The CARs engrafted in non-responders but did not proliferate.

“So the biomarker correlate of success is persistence and proliferation, in CLL at least,” Dr June said.

The investigators performed IGH next-generation sequencing and found no detectable CLL clones in the complete responders, including 1 patient at 3.5 years and another at 4 years post-infusion.

“There was no clinically evident disease in these patients,” Dr June said, “and so the responses are durable.”

The team also believes that at least a subset of the cells remains functional because the patients still had B-cell aplasia.

The investigators have not observed a CD19 loss in any CLL patient who responded.

“Patients who have gone into remission stay in remission,” Dr June added.

Kinetics of delayed CR

Dr June discussed in detail Patient 10, whose response was somewhat different from the other complete responders. Patient 10 achieved a CR, but the response was delayed. It took 51 days after infusion, compared to about 10 days in the other complete responders.

Patient 10 was initially scored as a failure at the 28-day evaluation. Eventually, he had marked improvement, and, by a year, he was in CR.

He required hospitalization for tumor lysis syndrome and treatment with tocilizumab for cytokine release syndrome.

Patient 10 had a single cell that investigators surmise could have been responsible for the tumor elimination.

“In fact, on day 28, when he still had tumor, his CARs were polyclonal,” Dr June said. “So we stained and isolated his CARs by sorting, and, at time of tumor elimination, he had descendants of 1 CAR.”

Nevertheless, Patient 10’s response is durable. He is now 81 years old and remains engrafted with CAR19 cells.

Investigators hypothesize that the kinetics and CAR proliferation were so different in Patient 10 because Tet2 was disrupted by the integration of the CAR into the intronic region.

“What we don’t know is whether Tet2 was a passenger or a driver here,” Dr June observed. “Did it actually aid the function of the CAR cells or was it just a marker?”

He noted that Tet2 has been shown in acute myeloid leukemia to increase stem cell renewal, “and it may well have done that in this patient.”

Malaria-infected cell bursting

Image by Peter H. Seeberger

Researchers say they have identified a mechanism of multidrug resistance in malaria that represents a major threat to antimalarial drug policy.

The team exposed a strain of malaria parasites to artemisinin (the base compound for standard therapy) long-term and found the parasites developed widespread resistance to most other antimalarial drugs.

The group also discovered that this type of resistance cannot be detected by current assays.

Françoise Benoit-Vical, PhD, of Université de Toulouse in France, and his colleagues described this work in Emerging Infectious Diseases.

The researchers set out to study resistance mechanisms in Plasmodium falciparum parasites. So they exposed the parasites to artemisinin in vitro for 5 years.

Parasites that survived in the presence of artemisinin developed resistance to most other artemisinin-based or non-artemisinin-based antimalarial therapies, including partner molecules present in combination therapies used in endemic areas.

These parasites did not exhibit any known mutation in resistance genes. However, the researchers found the parasites could circumvent the toxic effect of the drugs by quiescence.

The parasites were able to suspend their development during exposure to antimalarial agents. As soon as they were no longer subjected to antimalarial therapy, they “woke up” and began to proliferate again.

The researchers also found that multidrug resistance based on this quiescence phenomenon cannot be detected by tests currently used to analyze parasitic resistance.

“In vitro tests carried out using the patient’s blood predict high sensitivity and, therefore, the treatment’s effectiveness, while parasites are resistant because they are quiescent,” Dr Benoit-Vical said.

“As such, it is essential to conduct research with relevant and appropriate tests in the field if the multi[drug]-resistant phenomenon that we identified in vitro is also present, in order to design therapeutic strategies accordingly.”

Malaria-infected cell bursting

Image by Peter H. Seeberger

Researchers say they have identified a mechanism of multidrug resistance in malaria that represents a major threat to antimalarial drug policy.

The team exposed a strain of malaria parasites to artemisinin (the base compound for standard therapy) long-term and found the parasites developed widespread resistance to most other antimalarial drugs.

The group also discovered that this type of resistance cannot be detected by current assays.

Françoise Benoit-Vical, PhD, of Université de Toulouse in France, and his colleagues described this work in Emerging Infectious Diseases.

The researchers set out to study resistance mechanisms in Plasmodium falciparum parasites. So they exposed the parasites to artemisinin in vitro for 5 years.

Parasites that survived in the presence of artemisinin developed resistance to most other artemisinin-based or non-artemisinin-based antimalarial therapies, including partner molecules present in combination therapies used in endemic areas.

These parasites did not exhibit any known mutation in resistance genes. However, the researchers found the parasites could circumvent the toxic effect of the drugs by quiescence.

The parasites were able to suspend their development during exposure to antimalarial agents. As soon as they were no longer subjected to antimalarial therapy, they “woke up” and began to proliferate again.

The researchers also found that multidrug resistance based on this quiescence phenomenon cannot be detected by tests currently used to analyze parasitic resistance.

“In vitro tests carried out using the patient’s blood predict high sensitivity and, therefore, the treatment’s effectiveness, while parasites are resistant because they are quiescent,” Dr Benoit-Vical said.

“As such, it is essential to conduct research with relevant and appropriate tests in the field if the multi[drug]-resistant phenomenon that we identified in vitro is also present, in order to design therapeutic strategies accordingly.”

Malaria-infected cell bursting

Image by Peter H. Seeberger

Researchers say they have identified a mechanism of multidrug resistance in malaria that represents a major threat to antimalarial drug policy.

The team exposed a strain of malaria parasites to artemisinin (the base compound for standard therapy) long-term and found the parasites developed widespread resistance to most other antimalarial drugs.

The group also discovered that this type of resistance cannot be detected by current assays.

Françoise Benoit-Vical, PhD, of Université de Toulouse in France, and his colleagues described this work in Emerging Infectious Diseases.

The researchers set out to study resistance mechanisms in Plasmodium falciparum parasites. So they exposed the parasites to artemisinin in vitro for 5 years.

Parasites that survived in the presence of artemisinin developed resistance to most other artemisinin-based or non-artemisinin-based antimalarial therapies, including partner molecules present in combination therapies used in endemic areas.

These parasites did not exhibit any known mutation in resistance genes. However, the researchers found the parasites could circumvent the toxic effect of the drugs by quiescence.

The parasites were able to suspend their development during exposure to antimalarial agents. As soon as they were no longer subjected to antimalarial therapy, they “woke up” and began to proliferate again.

The researchers also found that multidrug resistance based on this quiescence phenomenon cannot be detected by tests currently used to analyze parasitic resistance.

“In vitro tests carried out using the patient’s blood predict high sensitivity and, therefore, the treatment’s effectiveness, while parasites are resistant because they are quiescent,” Dr Benoit-Vical said.

“As such, it is essential to conduct research with relevant and appropriate tests in the field if the multi[drug]-resistant phenomenon that we identified in vitro is also present, in order to design therapeutic strategies accordingly.”