History buffs attending the American College of Surgeons (ACS) Clinical Congress 2016, October 16−20, in Washington, DC, should plan to participate in several events sponsored by the College’s Surgical History Group (SHG). Stop by the Archives booth in the ACS Resource Center of the Walter E. Washington Convention Center, and pick up this year’s premium, a packet of baseball-sized cards commemorating the first four ACS Presidents. Start collecting the first cards in this annual series. John A. Weigelt, MD, FACS, Milt & Lidy Lunda/Charles Aprahamian Professor of Trauma Surgery; professor and chief, division of trauma and critical care; and associate dean for quality, Medical College of Wisconsin, Milwaukee, and the 2015 recipient of the ACS Distinguished Service Award, will present a history of the Surgical Education and Self-Assessment Program at the Surgical History Group breakfast session, 7:00-8:00 am, Tuesday, October 18 in Room 204BC of the convention center. Attendees should plan to visit the more than 20 History of Surgery Posters, and attend the Panel Session, Three Pioneering African American Surgeons. Check the Program Book or meeting app for details, and find additional information about other SHG-sponsored events on the ACS website at https://www.facs.org/about-acs/archives/shg-events.

History buffs attending the American College of Surgeons (ACS) Clinical Congress 2016, October 16−20, in Washington, DC, should plan to participate in several events sponsored by the College’s Surgical History Group (SHG). Stop by the Archives booth in the ACS Resource Center of the Walter E. Washington Convention Center, and pick up this year’s premium, a packet of baseball-sized cards commemorating the first four ACS Presidents. Start collecting the first cards in this annual series. John A. Weigelt, MD, FACS, Milt & Lidy Lunda/Charles Aprahamian Professor of Trauma Surgery; professor and chief, division of trauma and critical care; and associate dean for quality, Medical College of Wisconsin, Milwaukee, and the 2015 recipient of the ACS Distinguished Service Award, will present a history of the Surgical Education and Self-Assessment Program at the Surgical History Group breakfast session, 7:00-8:00 am, Tuesday, October 18 in Room 204BC of the convention center. Attendees should plan to visit the more than 20 History of Surgery Posters, and attend the Panel Session, Three Pioneering African American Surgeons. Check the Program Book or meeting app for details, and find additional information about other SHG-sponsored events on the ACS website at https://www.facs.org/about-acs/archives/shg-events.

History buffs attending the American College of Surgeons (ACS) Clinical Congress 2016, October 16−20, in Washington, DC, should plan to participate in several events sponsored by the College’s Surgical History Group (SHG). Stop by the Archives booth in the ACS Resource Center of the Walter E. Washington Convention Center, and pick up this year’s premium, a packet of baseball-sized cards commemorating the first four ACS Presidents. Start collecting the first cards in this annual series. John A. Weigelt, MD, FACS, Milt & Lidy Lunda/Charles Aprahamian Professor of Trauma Surgery; professor and chief, division of trauma and critical care; and associate dean for quality, Medical College of Wisconsin, Milwaukee, and the 2015 recipient of the ACS Distinguished Service Award, will present a history of the Surgical Education and Self-Assessment Program at the Surgical History Group breakfast session, 7:00-8:00 am, Tuesday, October 18 in Room 204BC of the convention center. Attendees should plan to visit the more than 20 History of Surgery Posters, and attend the Panel Session, Three Pioneering African American Surgeons. Check the Program Book or meeting app for details, and find additional information about other SHG-sponsored events on the ACS website at https://www.facs.org/about-acs/archives/shg-events.

The American College of Surgeons Surgical Research Committee is accepting applications until February 24 for the 2017 Joan L. and Julius H. Jacobson II Promising Investigator Award. This award recognizes outstanding surgeons engaged in research, advancing the art and science of surgery, and demonstrating early promise of significant contributions to the practice of surgery and the safety of surgical patients.

This award is intended for surgeons who are at the “tipping point” of their research careers with a track record indicative of early promise and potential. Well-established surgeon-scientists are ineligible for the award.

For details on award criteria and nomination procedures, visit the Jacobson Promising Investigator Award website at https://www.facs.org/quality-programs/about/cqi/Jacobson.

The American College of Surgeons Surgical Research Committee is accepting applications until February 24 for the 2017 Joan L. and Julius H. Jacobson II Promising Investigator Award. This award recognizes outstanding surgeons engaged in research, advancing the art and science of surgery, and demonstrating early promise of significant contributions to the practice of surgery and the safety of surgical patients.

This award is intended for surgeons who are at the “tipping point” of their research careers with a track record indicative of early promise and potential. Well-established surgeon-scientists are ineligible for the award.

For details on award criteria and nomination procedures, visit the Jacobson Promising Investigator Award website at https://www.facs.org/quality-programs/about/cqi/Jacobson.

The American College of Surgeons Surgical Research Committee is accepting applications until February 24 for the 2017 Joan L. and Julius H. Jacobson II Promising Investigator Award. This award recognizes outstanding surgeons engaged in research, advancing the art and science of surgery, and demonstrating early promise of significant contributions to the practice of surgery and the safety of surgical patients.

This award is intended for surgeons who are at the “tipping point” of their research careers with a track record indicative of early promise and potential. Well-established surgeon-scientists are ineligible for the award.

For details on award criteria and nomination procedures, visit the Jacobson Promising Investigator Award website at https://www.facs.org/quality-programs/about/cqi/Jacobson.

BOSTON – For patients with resected brain metastases, stereotactic radiosurgery offers survival comparable with what’s seen with whole-brain radiotherapy, but with better quality of life and more effective preservation of cognitive function, investigators reported.

In the phase III N107C trial, there was no difference in overall survival between patients who were randomly assigned to undergo stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), but patients who underwent WBRT had a twofold greater decline in cognitive function, compared with patients who underwent SRS, Paul D. Brown, MD, a radiation oncologist at the Mayo Clinic in Rochester, Minn., reported at the annual meeting of the American Society for Radiation Oncology.

In a similar prospective, randomized study, Anita Mahajan, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston compared postoperative SRS after complete resection with observation alone in 128 patients, and found that although there was no difference in either distant brain metastases or overall survival, SRS was associated with significant improvements in local control.

“I think that going forward with the next patient I see with this scenario, I’m going to be a bit better informed and be able to inform my patient better of the trade-offs involved with regards to the decision of SRS vs. whole-brain radiotherapy,” commented George Rodrigues, MD, from the London (Ontario) Health Sciences Center in Canada. Dr. Rodrigues moderated a briefing during which Dr. Brown and Dr. Mahajan presented their data.

WBRT has been the standard of care for improving local control following surgical resection of brain metastases, but it does not offer a survival benefit and comes at a significant cost in side effects, including alopecia, fatigue, erythema, and, most distressing to patients, significant decline in cognitive function.

The precision of radiosurgery, on the other hand, allows the radiation dose to be concentrated on the surgical bed, limiting exposure of surrounding tissues and structures. For this reason, many centers have begun to adopt SRS for patients with resected brain metastases, but there is not level I evidence to back it up, Dr. Brown said.

WBRT vs. SRS

To rectify this situation, Dr. Brown and his colleagues at the Mayo Clinic and 47 other institutions conducted a clinical trial in 194 patients with one to four brain metastases.

Following surgical resection, the patients were stratified by age, duration of extracranial disease control, number of preoperative metastases, histology, maximum diameter of the resection cavity, and institution, and then randomly assigned to undergo either WBRT or SRS.

Patients were assessed for cognitive function (a coprimary endpoint with overall survival) at baseline and approximately every 3 months thereafter for up to 24 months. Other assessments included MRI scans, and FACT-Br (Functional Assessment of Cancer Therapy-Brain), a quality-of-life instrument.

After a median follow-up of 18.7 months, there was no difference in median overall survival, which was 11.5 months for WBRT and 11.8 months for SRS.

There was, however, a significant difference in cognitive deterioration–free survival, which was 2.8 months for WBRT vs. 3.3 months for SRS. The hazard ratio for WBRT was 2.05 (P = .0001). Cognitive deterioration–free survival rates at 6 months were 5.4% and 22.9%, respectively (P = .0012).

The declines in cognitive function were accounted for by significant differences in the Hopkins Verbal Learning Test (HVLT) domains of total and delayed recall and in the Trail Making Test (Part A).

Overall brain disease control was significantly better with WBRT than with SRS at 3 months (P = .003) and at 6 and 12 months (P less than .001 for each time point).

Surgical bed control was similar between the treatment groups at 6 and 12 months, but was significantly better with WBRT at 12 months, with surgical bed relapse occurring in 21.8% and 44.4% of patients, respectively.

Patients treated with SRS reported significantly better physical well being at 3 and 6 months (P = .002 and .014, respectively). There were 18 grade 3 or greater radiation-related adverse events among patients treated with WBRT, compared with 7 among patients treated with SRS.

SRS vs. observation

In the MD Anderson study, 45% of patients who underwent observation alone had local control of disease at 12 months, compared with 72% treated with SRS. The hazard ratio for SRS was 0.46 (P = .01). The median time to local recurrence was 7.6 months among patients on observation only, but no time point was reached for SRS-treated patients.

The evidence from the two trials suggests that “radiosurgery is a, but not the, standard of care following resection for brain metastasis,” said Vinai Gondi, MD, of the Northwestern Medicine Cancer Center in Warrenville, Ill., the invited discussant.

“While the MD Anderson trial clearly demonstrated that radiosurgery reduces the risk of surgical bed relapse, the N107C trial demonstrated a 44% risk of surgical bed relapse, a rate that is arguably too high in regards to the long survival of resected brain metastasis patients, and it also challenges and risks the resection of surgical bed relapse following radiosurgery,” he said.

The N107C trial was sponsored by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. The MD Anderson trial was funded by a Cancer Center Grant. Dr. Brown, Dr. Mahajan, and Dr. Rodrigues reported no conflicts of interest.

BOSTON – For patients with resected brain metastases, stereotactic radiosurgery offers survival comparable with what’s seen with whole-brain radiotherapy, but with better quality of life and more effective preservation of cognitive function, investigators reported.

In the phase III N107C trial, there was no difference in overall survival between patients who were randomly assigned to undergo stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), but patients who underwent WBRT had a twofold greater decline in cognitive function, compared with patients who underwent SRS, Paul D. Brown, MD, a radiation oncologist at the Mayo Clinic in Rochester, Minn., reported at the annual meeting of the American Society for Radiation Oncology.

In a similar prospective, randomized study, Anita Mahajan, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston compared postoperative SRS after complete resection with observation alone in 128 patients, and found that although there was no difference in either distant brain metastases or overall survival, SRS was associated with significant improvements in local control.

“I think that going forward with the next patient I see with this scenario, I’m going to be a bit better informed and be able to inform my patient better of the trade-offs involved with regards to the decision of SRS vs. whole-brain radiotherapy,” commented George Rodrigues, MD, from the London (Ontario) Health Sciences Center in Canada. Dr. Rodrigues moderated a briefing during which Dr. Brown and Dr. Mahajan presented their data.

WBRT has been the standard of care for improving local control following surgical resection of brain metastases, but it does not offer a survival benefit and comes at a significant cost in side effects, including alopecia, fatigue, erythema, and, most distressing to patients, significant decline in cognitive function.

The precision of radiosurgery, on the other hand, allows the radiation dose to be concentrated on the surgical bed, limiting exposure of surrounding tissues and structures. For this reason, many centers have begun to adopt SRS for patients with resected brain metastases, but there is not level I evidence to back it up, Dr. Brown said.

WBRT vs. SRS

To rectify this situation, Dr. Brown and his colleagues at the Mayo Clinic and 47 other institutions conducted a clinical trial in 194 patients with one to four brain metastases.

Following surgical resection, the patients were stratified by age, duration of extracranial disease control, number of preoperative metastases, histology, maximum diameter of the resection cavity, and institution, and then randomly assigned to undergo either WBRT or SRS.

Patients were assessed for cognitive function (a coprimary endpoint with overall survival) at baseline and approximately every 3 months thereafter for up to 24 months. Other assessments included MRI scans, and FACT-Br (Functional Assessment of Cancer Therapy-Brain), a quality-of-life instrument.

After a median follow-up of 18.7 months, there was no difference in median overall survival, which was 11.5 months for WBRT and 11.8 months for SRS.

There was, however, a significant difference in cognitive deterioration–free survival, which was 2.8 months for WBRT vs. 3.3 months for SRS. The hazard ratio for WBRT was 2.05 (P = .0001). Cognitive deterioration–free survival rates at 6 months were 5.4% and 22.9%, respectively (P = .0012).

The declines in cognitive function were accounted for by significant differences in the Hopkins Verbal Learning Test (HVLT) domains of total and delayed recall and in the Trail Making Test (Part A).

Overall brain disease control was significantly better with WBRT than with SRS at 3 months (P = .003) and at 6 and 12 months (P less than .001 for each time point).

Surgical bed control was similar between the treatment groups at 6 and 12 months, but was significantly better with WBRT at 12 months, with surgical bed relapse occurring in 21.8% and 44.4% of patients, respectively.

Patients treated with SRS reported significantly better physical well being at 3 and 6 months (P = .002 and .014, respectively). There were 18 grade 3 or greater radiation-related adverse events among patients treated with WBRT, compared with 7 among patients treated with SRS.

SRS vs. observation

In the MD Anderson study, 45% of patients who underwent observation alone had local control of disease at 12 months, compared with 72% treated with SRS. The hazard ratio for SRS was 0.46 (P = .01). The median time to local recurrence was 7.6 months among patients on observation only, but no time point was reached for SRS-treated patients.

The evidence from the two trials suggests that “radiosurgery is a, but not the, standard of care following resection for brain metastasis,” said Vinai Gondi, MD, of the Northwestern Medicine Cancer Center in Warrenville, Ill., the invited discussant.

“While the MD Anderson trial clearly demonstrated that radiosurgery reduces the risk of surgical bed relapse, the N107C trial demonstrated a 44% risk of surgical bed relapse, a rate that is arguably too high in regards to the long survival of resected brain metastasis patients, and it also challenges and risks the resection of surgical bed relapse following radiosurgery,” he said.

The N107C trial was sponsored by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. The MD Anderson trial was funded by a Cancer Center Grant. Dr. Brown, Dr. Mahajan, and Dr. Rodrigues reported no conflicts of interest.

BOSTON – For patients with resected brain metastases, stereotactic radiosurgery offers survival comparable with what’s seen with whole-brain radiotherapy, but with better quality of life and more effective preservation of cognitive function, investigators reported.

In the phase III N107C trial, there was no difference in overall survival between patients who were randomly assigned to undergo stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), but patients who underwent WBRT had a twofold greater decline in cognitive function, compared with patients who underwent SRS, Paul D. Brown, MD, a radiation oncologist at the Mayo Clinic in Rochester, Minn., reported at the annual meeting of the American Society for Radiation Oncology.

In a similar prospective, randomized study, Anita Mahajan, MD, and colleagues from the University of Texas MD Anderson Cancer Center in Houston compared postoperative SRS after complete resection with observation alone in 128 patients, and found that although there was no difference in either distant brain metastases or overall survival, SRS was associated with significant improvements in local control.

“I think that going forward with the next patient I see with this scenario, I’m going to be a bit better informed and be able to inform my patient better of the trade-offs involved with regards to the decision of SRS vs. whole-brain radiotherapy,” commented George Rodrigues, MD, from the London (Ontario) Health Sciences Center in Canada. Dr. Rodrigues moderated a briefing during which Dr. Brown and Dr. Mahajan presented their data.

WBRT has been the standard of care for improving local control following surgical resection of brain metastases, but it does not offer a survival benefit and comes at a significant cost in side effects, including alopecia, fatigue, erythema, and, most distressing to patients, significant decline in cognitive function.

The precision of radiosurgery, on the other hand, allows the radiation dose to be concentrated on the surgical bed, limiting exposure of surrounding tissues and structures. For this reason, many centers have begun to adopt SRS for patients with resected brain metastases, but there is not level I evidence to back it up, Dr. Brown said.

WBRT vs. SRS

To rectify this situation, Dr. Brown and his colleagues at the Mayo Clinic and 47 other institutions conducted a clinical trial in 194 patients with one to four brain metastases.

Following surgical resection, the patients were stratified by age, duration of extracranial disease control, number of preoperative metastases, histology, maximum diameter of the resection cavity, and institution, and then randomly assigned to undergo either WBRT or SRS.

Patients were assessed for cognitive function (a coprimary endpoint with overall survival) at baseline and approximately every 3 months thereafter for up to 24 months. Other assessments included MRI scans, and FACT-Br (Functional Assessment of Cancer Therapy-Brain), a quality-of-life instrument.

After a median follow-up of 18.7 months, there was no difference in median overall survival, which was 11.5 months for WBRT and 11.8 months for SRS.

There was, however, a significant difference in cognitive deterioration–free survival, which was 2.8 months for WBRT vs. 3.3 months for SRS. The hazard ratio for WBRT was 2.05 (P = .0001). Cognitive deterioration–free survival rates at 6 months were 5.4% and 22.9%, respectively (P = .0012).

The declines in cognitive function were accounted for by significant differences in the Hopkins Verbal Learning Test (HVLT) domains of total and delayed recall and in the Trail Making Test (Part A).

Overall brain disease control was significantly better with WBRT than with SRS at 3 months (P = .003) and at 6 and 12 months (P less than .001 for each time point).

Surgical bed control was similar between the treatment groups at 6 and 12 months, but was significantly better with WBRT at 12 months, with surgical bed relapse occurring in 21.8% and 44.4% of patients, respectively.

Patients treated with SRS reported significantly better physical well being at 3 and 6 months (P = .002 and .014, respectively). There were 18 grade 3 or greater radiation-related adverse events among patients treated with WBRT, compared with 7 among patients treated with SRS.

SRS vs. observation

In the MD Anderson study, 45% of patients who underwent observation alone had local control of disease at 12 months, compared with 72% treated with SRS. The hazard ratio for SRS was 0.46 (P = .01). The median time to local recurrence was 7.6 months among patients on observation only, but no time point was reached for SRS-treated patients.

The evidence from the two trials suggests that “radiosurgery is a, but not the, standard of care following resection for brain metastasis,” said Vinai Gondi, MD, of the Northwestern Medicine Cancer Center in Warrenville, Ill., the invited discussant.

“While the MD Anderson trial clearly demonstrated that radiosurgery reduces the risk of surgical bed relapse, the N107C trial demonstrated a 44% risk of surgical bed relapse, a rate that is arguably too high in regards to the long survival of resected brain metastasis patients, and it also challenges and risks the resection of surgical bed relapse following radiosurgery,” he said.

The N107C trial was sponsored by the National Cancer Institute and the Alliance for Clinical Trials in Oncology. The MD Anderson trial was funded by a Cancer Center Grant. Dr. Brown, Dr. Mahajan, and Dr. Rodrigues reported no conflicts of interest.

A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.

The frequency of safety monitoring for HIV pre-exposure prophylaxis (PrEP) might need to be different between age groups, according to a recent study, and pharmacological measures can monitor for toxic effects as well as adherence.

©alexskopje/ThinkStock.com

A European research group found a beneficial effect of starting antiretroviral therapy before adolescence in perinatally infected individuals, and starting young people on boosted protease inhibitors, to maximize treatment response during this transitional stage of development.

Chinese investigators found that an online social entrepreneurship testing (SET) model to promote HIV and syphilis self-testing among Chinese men who have sex with men was acceptable and feasible, and they say that the model adds a new testing platform to the current testing service system.

A review analysis found that dolutegravir 50 mg given once daily, combined with an active background drug, is a better choice than raltegravir- or efavirenz-based regimens for treatment of HIV-1 infection, in terms of both efficacy and safety.

A recent study found that HIV suppression restores lung mucosal HIV-specific CD4⁺ T-cell multifunctional immunity and CD4:CD8 balance, often resolving CD8⁺ alveolitis in active smokers.

A study in Clinical Infectious Diseases found that only the Framingham general cardiovascular Risk Score (FRS) accurately estimated the risk of cardiovascular disease risk events in HIV patients, while the American College of Cardiology/American Heart Association Pooled Cohort equations (PCE), and the Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study equation underestimated risk.

A study in AIDS Care found a high burden of mental health disorders among harder-to-reach people living with HIV/AIDS (PHA), and suggests that PHA with at least one mental health disorder diagnosis are disproportionately affected by sexual violence and stigma.

Neurocognitive declines in HIV-positive patients may vary by domains of functioning and disparities may exist across subpopulations of the seropositive aging population, according to a recent study, and these challenges may exist even in those actively engaged in HIV care.

A high rate of recent HIV infection is potentially resulting in progressive deterioration of the overall HIV epidemic among men who have sex with men in China, according to a study in Infectious Diseases of Poverty. The authors said targeted interventions to address high-risk men who have sex with men including those having multiple partners, history of recreational drug use, and syphilis or HSV-2 infection are needed.

A recent study indicated that the variability in estimates of spontaneous viral clearance of hepatitis C virus infection – between HIV-positive men who have sex with men and people who inject drugs – suggests the impact of HIV coinfection and HCV reinfection.

A study published in the journal AIDS found that despite substantially higher CD4% at initiation of antiretroviral therapy, viral suppression was significantly slower among infants than older children.

Grip strength decline is accelerated in HIV-infected men, which may signal decreased life expectancy and lower quality of life with aging, according to an analysis by the Multicenter AIDS Cohort Study.

A study in HIV Medicine found that reference curves for CD4 T-cell count response aid the evaluation of the immune response in HIV-positive patients early after antiretroviral therapy initiation that leads to viral control.

According to WHO standards, Rwanda antenatal clinic HIV serosurveillance is ready to transition to prevention of mother to child transmission (PMTCT)-based serosurveillance.

Oxidized lipoproteins may contribute to persistent immune activation in HIV patients on antiretroviral therapy, a new study found.

A French study found that the rate of patients failing to return for the results of HIV, HBV, HCV, and syphilis testing is a problem, but the use of currently available technologies, such as phone texting, might be a partial solution in conjunction with rapid tests for diagnosis.

A 12-city U.S. research project on pre-exposure prophylaxis for HIV found that young men who have sex with men may need PrEP access in youth-friendly settings with tailored adherence support and potentially augmented visit schedules.

[email protected]

On Twitter @richpizzi

A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.

The frequency of safety monitoring for HIV pre-exposure prophylaxis (PrEP) might need to be different between age groups, according to a recent study, and pharmacological measures can monitor for toxic effects as well as adherence.

©alexskopje/ThinkStock.com

A European research group found a beneficial effect of starting antiretroviral therapy before adolescence in perinatally infected individuals, and starting young people on boosted protease inhibitors, to maximize treatment response during this transitional stage of development.

Chinese investigators found that an online social entrepreneurship testing (SET) model to promote HIV and syphilis self-testing among Chinese men who have sex with men was acceptable and feasible, and they say that the model adds a new testing platform to the current testing service system.

A review analysis found that dolutegravir 50 mg given once daily, combined with an active background drug, is a better choice than raltegravir- or efavirenz-based regimens for treatment of HIV-1 infection, in terms of both efficacy and safety.

A recent study found that HIV suppression restores lung mucosal HIV-specific CD4⁺ T-cell multifunctional immunity and CD4:CD8 balance, often resolving CD8⁺ alveolitis in active smokers.

A study in Clinical Infectious Diseases found that only the Framingham general cardiovascular Risk Score (FRS) accurately estimated the risk of cardiovascular disease risk events in HIV patients, while the American College of Cardiology/American Heart Association Pooled Cohort equations (PCE), and the Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study equation underestimated risk.

A study in AIDS Care found a high burden of mental health disorders among harder-to-reach people living with HIV/AIDS (PHA), and suggests that PHA with at least one mental health disorder diagnosis are disproportionately affected by sexual violence and stigma.

Neurocognitive declines in HIV-positive patients may vary by domains of functioning and disparities may exist across subpopulations of the seropositive aging population, according to a recent study, and these challenges may exist even in those actively engaged in HIV care.

A high rate of recent HIV infection is potentially resulting in progressive deterioration of the overall HIV epidemic among men who have sex with men in China, according to a study in Infectious Diseases of Poverty. The authors said targeted interventions to address high-risk men who have sex with men including those having multiple partners, history of recreational drug use, and syphilis or HSV-2 infection are needed.

A recent study indicated that the variability in estimates of spontaneous viral clearance of hepatitis C virus infection – between HIV-positive men who have sex with men and people who inject drugs – suggests the impact of HIV coinfection and HCV reinfection.

A study published in the journal AIDS found that despite substantially higher CD4% at initiation of antiretroviral therapy, viral suppression was significantly slower among infants than older children.

Grip strength decline is accelerated in HIV-infected men, which may signal decreased life expectancy and lower quality of life with aging, according to an analysis by the Multicenter AIDS Cohort Study.

A study in HIV Medicine found that reference curves for CD4 T-cell count response aid the evaluation of the immune response in HIV-positive patients early after antiretroviral therapy initiation that leads to viral control.

According to WHO standards, Rwanda antenatal clinic HIV serosurveillance is ready to transition to prevention of mother to child transmission (PMTCT)-based serosurveillance.

Oxidized lipoproteins may contribute to persistent immune activation in HIV patients on antiretroviral therapy, a new study found.

A French study found that the rate of patients failing to return for the results of HIV, HBV, HCV, and syphilis testing is a problem, but the use of currently available technologies, such as phone texting, might be a partial solution in conjunction with rapid tests for diagnosis.

A 12-city U.S. research project on pre-exposure prophylaxis for HIV found that young men who have sex with men may need PrEP access in youth-friendly settings with tailored adherence support and potentially augmented visit schedules.

[email protected]

On Twitter @richpizzi

A great volume of HIV and AIDS research enters the medical literature every month. It’s difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.

The frequency of safety monitoring for HIV pre-exposure prophylaxis (PrEP) might need to be different between age groups, according to a recent study, and pharmacological measures can monitor for toxic effects as well as adherence.

©alexskopje/ThinkStock.com

A European research group found a beneficial effect of starting antiretroviral therapy before adolescence in perinatally infected individuals, and starting young people on boosted protease inhibitors, to maximize treatment response during this transitional stage of development.

Chinese investigators found that an online social entrepreneurship testing (SET) model to promote HIV and syphilis self-testing among Chinese men who have sex with men was acceptable and feasible, and they say that the model adds a new testing platform to the current testing service system.

A review analysis found that dolutegravir 50 mg given once daily, combined with an active background drug, is a better choice than raltegravir- or efavirenz-based regimens for treatment of HIV-1 infection, in terms of both efficacy and safety.

A recent study found that HIV suppression restores lung mucosal HIV-specific CD4⁺ T-cell multifunctional immunity and CD4:CD8 balance, often resolving CD8⁺ alveolitis in active smokers.

A study in Clinical Infectious Diseases found that only the Framingham general cardiovascular Risk Score (FRS) accurately estimated the risk of cardiovascular disease risk events in HIV patients, while the American College of Cardiology/American Heart Association Pooled Cohort equations (PCE), and the Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study equation underestimated risk.

A study in AIDS Care found a high burden of mental health disorders among harder-to-reach people living with HIV/AIDS (PHA), and suggests that PHA with at least one mental health disorder diagnosis are disproportionately affected by sexual violence and stigma.

Neurocognitive declines in HIV-positive patients may vary by domains of functioning and disparities may exist across subpopulations of the seropositive aging population, according to a recent study, and these challenges may exist even in those actively engaged in HIV care.

A high rate of recent HIV infection is potentially resulting in progressive deterioration of the overall HIV epidemic among men who have sex with men in China, according to a study in Infectious Diseases of Poverty. The authors said targeted interventions to address high-risk men who have sex with men including those having multiple partners, history of recreational drug use, and syphilis or HSV-2 infection are needed.

A recent study indicated that the variability in estimates of spontaneous viral clearance of hepatitis C virus infection – between HIV-positive men who have sex with men and people who inject drugs – suggests the impact of HIV coinfection and HCV reinfection.

A study published in the journal AIDS found that despite substantially higher CD4% at initiation of antiretroviral therapy, viral suppression was significantly slower among infants than older children.

Grip strength decline is accelerated in HIV-infected men, which may signal decreased life expectancy and lower quality of life with aging, according to an analysis by the Multicenter AIDS Cohort Study.

A study in HIV Medicine found that reference curves for CD4 T-cell count response aid the evaluation of the immune response in HIV-positive patients early after antiretroviral therapy initiation that leads to viral control.

According to WHO standards, Rwanda antenatal clinic HIV serosurveillance is ready to transition to prevention of mother to child transmission (PMTCT)-based serosurveillance.

Oxidized lipoproteins may contribute to persistent immune activation in HIV patients on antiretroviral therapy, a new study found.

A French study found that the rate of patients failing to return for the results of HIV, HBV, HCV, and syphilis testing is a problem, but the use of currently available technologies, such as phone texting, might be a partial solution in conjunction with rapid tests for diagnosis.

A 12-city U.S. research project on pre-exposure prophylaxis for HIV found that young men who have sex with men may need PrEP access in youth-friendly settings with tailored adherence support and potentially augmented visit schedules.

[email protected]

On Twitter @richpizzi

Pre-exposure prophylaxis (PrEP) therapy is safe for HIV-uninfected women breastfeeding their infants, according to a study in PLOS Medicine.

As PrEP becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking the drugs, reported Kenneth Mugwanya, MBChB, PhD, of the University of Washington, Seattle, and his associates (PLOS Med. 2016 Sep 27. doi: 10.1371/journal.pmed.1002132).

oksun70/ThinkStock

The purpose of this small, prospective short-term trialwas to quantify drug levels in maternal blood samples, breast milk, and infant blood samples to begin to understand if PrEP is safe for use in pregnant or breastfeeding women at high risk for contracting HIV.

Antiretroviral PrEP with 300 mg tenofovir disoproxil fumarate and 200 mg emtricitabine was administered to 50 HIV-uninfected breastfeeding mothers through daily directly observed therapy for 10 consecutive days and then discontinued thereafter. All mothers were African and resided in Kenya or Uganda. Median maternal age was 25 years; 48% of infants were younger than 12 weeks and 52% were between 13 and 24 weeks of age. Across the study cohort, the median daily frequency of breastfeeding was 15 times.

Maternal blood and breast milk samples were collected and analyzed for drug concentrations at days 7 and 10 of the study. Peak concentration samples, collected 1-2 hours after PrEP administration, and trough concentration levels, collected 23-24 hours after PrEP dose, were collected on day 7 and day 10. Infant blood samples were collected only once, on day 7.

In maternal blood samples, tenofovir was detected at concentrations consistent with steady-state use (median peak concentration, 152.0 ng/mL). In breast milk, tenofovir was present in significantly lower concentrations (3.2 ng/mL). Emtricitabine was also detected at concentrations consistent with steady-state use in maternal blood samples (median peak concentration, 267.5 ng/mL); however, unlike tenofovir, emtricitabine concentration in breast milk was similar to peak plasma concentrations (212.5 ng/mL). Tenofovir was undetectable in 46 of 49 (94%) infant plasma samples. For the three infants with detectable tenofovir, the plasma concentrations were 0.9, 0.9, and 17.4 ng/mL, corresponding body weights were 6.4, 5.8, and 6.2 kg, and their maternal milk tenofovir concentrations were “modestly greater” than the median at 6.57, 3.64, and 4.05 ng/mL, respectively.

Emtricitabine, on the other hand, was detectable in 47 of 49 (96%) infant plasma samples with a median concentration of 13.2 ng/mL.

“The estimated daily tenofovir and emtricitabine doses ingested by the infant through breastfeeding were 12,500-fold and 200-fold, respectively, lower than the proposed daily pediatric dose for prophylaxis against vertical HIV acquisition. Thus, infants had low exposures to tenofovir and emtricitabine, which would not be expected to pose substantial safety risk to infants of mothers who use PrEP during breastfeeding,” Dr. Mugwanya and his associates wrote.

“These data provide evidence suggesting that this PrEP regimen can be safely used during breastfeeding, which is informative for clinical guidelines for women who are at substantial risk of HIV during pregnancy and the postpartum period,” the researchers concluded.

This study was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health. The authors did not report disclosures.

[email protected]

On Twitter @jessnicolecraig

Pre-exposure prophylaxis (PrEP) therapy is safe for HIV-uninfected women breastfeeding their infants, according to a study in PLOS Medicine.

As PrEP becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking the drugs, reported Kenneth Mugwanya, MBChB, PhD, of the University of Washington, Seattle, and his associates (PLOS Med. 2016 Sep 27. doi: 10.1371/journal.pmed.1002132).

oksun70/ThinkStock

The purpose of this small, prospective short-term trialwas to quantify drug levels in maternal blood samples, breast milk, and infant blood samples to begin to understand if PrEP is safe for use in pregnant or breastfeeding women at high risk for contracting HIV.

Antiretroviral PrEP with 300 mg tenofovir disoproxil fumarate and 200 mg emtricitabine was administered to 50 HIV-uninfected breastfeeding mothers through daily directly observed therapy for 10 consecutive days and then discontinued thereafter. All mothers were African and resided in Kenya or Uganda. Median maternal age was 25 years; 48% of infants were younger than 12 weeks and 52% were between 13 and 24 weeks of age. Across the study cohort, the median daily frequency of breastfeeding was 15 times.

Maternal blood and breast milk samples were collected and analyzed for drug concentrations at days 7 and 10 of the study. Peak concentration samples, collected 1-2 hours after PrEP administration, and trough concentration levels, collected 23-24 hours after PrEP dose, were collected on day 7 and day 10. Infant blood samples were collected only once, on day 7.

In maternal blood samples, tenofovir was detected at concentrations consistent with steady-state use (median peak concentration, 152.0 ng/mL). In breast milk, tenofovir was present in significantly lower concentrations (3.2 ng/mL). Emtricitabine was also detected at concentrations consistent with steady-state use in maternal blood samples (median peak concentration, 267.5 ng/mL); however, unlike tenofovir, emtricitabine concentration in breast milk was similar to peak plasma concentrations (212.5 ng/mL). Tenofovir was undetectable in 46 of 49 (94%) infant plasma samples. For the three infants with detectable tenofovir, the plasma concentrations were 0.9, 0.9, and 17.4 ng/mL, corresponding body weights were 6.4, 5.8, and 6.2 kg, and their maternal milk tenofovir concentrations were “modestly greater” than the median at 6.57, 3.64, and 4.05 ng/mL, respectively.

Emtricitabine, on the other hand, was detectable in 47 of 49 (96%) infant plasma samples with a median concentration of 13.2 ng/mL.

“The estimated daily tenofovir and emtricitabine doses ingested by the infant through breastfeeding were 12,500-fold and 200-fold, respectively, lower than the proposed daily pediatric dose for prophylaxis against vertical HIV acquisition. Thus, infants had low exposures to tenofovir and emtricitabine, which would not be expected to pose substantial safety risk to infants of mothers who use PrEP during breastfeeding,” Dr. Mugwanya and his associates wrote.

“These data provide evidence suggesting that this PrEP regimen can be safely used during breastfeeding, which is informative for clinical guidelines for women who are at substantial risk of HIV during pregnancy and the postpartum period,” the researchers concluded.

This study was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health. The authors did not report disclosures.

[email protected]

On Twitter @jessnicolecraig

Pre-exposure prophylaxis (PrEP) therapy is safe for HIV-uninfected women breastfeeding their infants, according to a study in PLOS Medicine.

As PrEP becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking the drugs, reported Kenneth Mugwanya, MBChB, PhD, of the University of Washington, Seattle, and his associates (PLOS Med. 2016 Sep 27. doi: 10.1371/journal.pmed.1002132).

oksun70/ThinkStock

The purpose of this small, prospective short-term trialwas to quantify drug levels in maternal blood samples, breast milk, and infant blood samples to begin to understand if PrEP is safe for use in pregnant or breastfeeding women at high risk for contracting HIV.

Antiretroviral PrEP with 300 mg tenofovir disoproxil fumarate and 200 mg emtricitabine was administered to 50 HIV-uninfected breastfeeding mothers through daily directly observed therapy for 10 consecutive days and then discontinued thereafter. All mothers were African and resided in Kenya or Uganda. Median maternal age was 25 years; 48% of infants were younger than 12 weeks and 52% were between 13 and 24 weeks of age. Across the study cohort, the median daily frequency of breastfeeding was 15 times.

Maternal blood and breast milk samples were collected and analyzed for drug concentrations at days 7 and 10 of the study. Peak concentration samples, collected 1-2 hours after PrEP administration, and trough concentration levels, collected 23-24 hours after PrEP dose, were collected on day 7 and day 10. Infant blood samples were collected only once, on day 7.

In maternal blood samples, tenofovir was detected at concentrations consistent with steady-state use (median peak concentration, 152.0 ng/mL). In breast milk, tenofovir was present in significantly lower concentrations (3.2 ng/mL). Emtricitabine was also detected at concentrations consistent with steady-state use in maternal blood samples (median peak concentration, 267.5 ng/mL); however, unlike tenofovir, emtricitabine concentration in breast milk was similar to peak plasma concentrations (212.5 ng/mL). Tenofovir was undetectable in 46 of 49 (94%) infant plasma samples. For the three infants with detectable tenofovir, the plasma concentrations were 0.9, 0.9, and 17.4 ng/mL, corresponding body weights were 6.4, 5.8, and 6.2 kg, and their maternal milk tenofovir concentrations were “modestly greater” than the median at 6.57, 3.64, and 4.05 ng/mL, respectively.

Emtricitabine, on the other hand, was detectable in 47 of 49 (96%) infant plasma samples with a median concentration of 13.2 ng/mL.

“The estimated daily tenofovir and emtricitabine doses ingested by the infant through breastfeeding were 12,500-fold and 200-fold, respectively, lower than the proposed daily pediatric dose for prophylaxis against vertical HIV acquisition. Thus, infants had low exposures to tenofovir and emtricitabine, which would not be expected to pose substantial safety risk to infants of mothers who use PrEP during breastfeeding,” Dr. Mugwanya and his associates wrote.

“These data provide evidence suggesting that this PrEP regimen can be safely used during breastfeeding, which is informative for clinical guidelines for women who are at substantial risk of HIV during pregnancy and the postpartum period,” the researchers concluded.

This study was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health. The authors did not report disclosures.

[email protected]

On Twitter @jessnicolecraig

ORLANDO – Transitioning patients with hemophilia from standard clotting factor concentrates to newer extended half-life products takes planning, education, and a little patience, but the payoff can be better hemostasis, a hemophilia treatment specialist said.

“Real-world experience shows us that you can maintain effective protection with less infusion with these new products, but we also know that each person should be evaluated individually when determining what their specific optimal treatment is,” said Jennifer Maahs, a hemophilia nurse practitioner at the Indiana Hemophilia and Thrombosis Center in Indianapolis.

Staff and patient education about the proper use of newer extended half-life (EHL) products is the key to success, she added in an oral session at the World Federation of Hemophilia World Congress.

The new EHL products allow for longer intervals between doses, especially with EHL recombinant factor IX used to treat hemophilia B. Prophylaxis with standard factor IX concentrates requires doses of 25-40 IU/kg twice weekly; in contrasts, EHL products can be given in various doses based on patient responses of either 50 IU/kg every 7 days, 100 IU/kg every 10 days, 25-40 IU/kg every 7 days, or 50-75 IU/kg every 14 days.

In general, the longer intervals between dosing occur in adults; young children tend to require more frequent dosing and have lower levels of factor recovery, she noted.

Extended Experience

Her center currently has more than 100 patients maintained on prolonged half-life factor VIII and factor IX products.

“We have really learned a lot of lessons along the way, and we have had to modify our approach based on these lessons,” she said. “Each patient situation is unique, and everything needs to be individualized.”

Staff review the published literature to educate themselves on the EHL products and prepare answers to expected questions from patients. Ms. Maahs suggested identifying key staff who are best equipped to answer specific questions.

“From a patient standpoint, we’ve developed a patient notification letter, so for any new product that comes out – for example a new factor VIII product – the notification gets sent out factor VIII patients, and we do that for every new product that comes out,” she said.

PK OK

Pharmacokinetic (PK) analyses may also be helpful in transitioning patients to EHL products.

To test patient responses to new products, her center tests patients for recovery from 15 minutes to 1 hour post-infusion, which will provide information about how the patient may respond to the product during a bleeding episode.

If the patient is on prophylaxis they will evaluate trough effectiveness to determine that patient’s responsiveness at the lowest level prior to the next infusion. Testing at other time points may be required based on the patient’s individual clinical history.

Center staff talk with each patient to discuss his needs and capabilities. If the patient is currently being managed with on-demand therapy, the talk may center on obstacles to utilization of prophylaxis and the patient’s desired infusion interval.

For patients currently on prophylaxis, they discuss the current regimen frequency and dose and assess how well it’s working. Staff members also provide information about alternative approaches to therapy, and ask patients specifically about their activity levels and dates of activity, compared with currently scheduled infusion days.

Patients are also educated about the reconstitution requirements for the new product, and are told to use up any remaining concentrates before switching over to the new product.

“As we move forward, within 2 to 4 weeks of starting a new therapy, we like to obtain a trough to see how their prophylaxis is working. At that time we ask how have you been doing on the new product, are you having any breakthrough bleeding, and how are you feeling about it,” Ms. Maahs said.

Weekly phone calls to the patient during the first month are also very helpful for reinforcing information about dosing regimens for bleeding episodes, reminding patients to call in if they experience a lead, and encouraging them to keep a treatment log. The phone call can also be helpful in identifying potential product-related reactions or other issues, she said.

‘Big impact’

“What’s the impact that we’ve seen? With factor IX, it has been really big. Previous on-demand patients have agreed that, ‘gosh, I’m infusing a couple of times a month anyway,’ so starting an every 14-day prophylactic regimen seems pretty reasonable,” she said.

“We’ve had infusion schedules in children change from twice weekly to once weekly and that has really decreased the burden of disease,” she added.

A few adults, however, have gone back to standard half-life products because of concerns that they would not be able to infuse when they thought they needed treatment, she noted.

The impact of the EHL factor VIII products has been smaller, although it has allowed slight increases in the dosing intervals (from every other day to every third day in children, for example), and has overall decreased the average number of monthly infusions from about 15 to about 10.

Some adolescents and young adults, who often have been on prophylaxis for all of their lives, have experienced absent or only minimal joint disease, and some have been able to extend their dosing intervals from every 4 to every 5 to 7 days, she said.

Ms. Maahs disclosed serving on advisory committees to Baxalta, Novo Nordisk, Biogen, Genentech, and CSL, and receiving honoraria related to those activities.

ORLANDO – Transitioning patients with hemophilia from standard clotting factor concentrates to newer extended half-life products takes planning, education, and a little patience, but the payoff can be better hemostasis, a hemophilia treatment specialist said.

“Real-world experience shows us that you can maintain effective protection with less infusion with these new products, but we also know that each person should be evaluated individually when determining what their specific optimal treatment is,” said Jennifer Maahs, a hemophilia nurse practitioner at the Indiana Hemophilia and Thrombosis Center in Indianapolis.

Staff and patient education about the proper use of newer extended half-life (EHL) products is the key to success, she added in an oral session at the World Federation of Hemophilia World Congress.

The new EHL products allow for longer intervals between doses, especially with EHL recombinant factor IX used to treat hemophilia B. Prophylaxis with standard factor IX concentrates requires doses of 25-40 IU/kg twice weekly; in contrasts, EHL products can be given in various doses based on patient responses of either 50 IU/kg every 7 days, 100 IU/kg every 10 days, 25-40 IU/kg every 7 days, or 50-75 IU/kg every 14 days.

In general, the longer intervals between dosing occur in adults; young children tend to require more frequent dosing and have lower levels of factor recovery, she noted.

Extended Experience

Her center currently has more than 100 patients maintained on prolonged half-life factor VIII and factor IX products.

“We have really learned a lot of lessons along the way, and we have had to modify our approach based on these lessons,” she said. “Each patient situation is unique, and everything needs to be individualized.”

Staff review the published literature to educate themselves on the EHL products and prepare answers to expected questions from patients. Ms. Maahs suggested identifying key staff who are best equipped to answer specific questions.

“From a patient standpoint, we’ve developed a patient notification letter, so for any new product that comes out – for example a new factor VIII product – the notification gets sent out factor VIII patients, and we do that for every new product that comes out,” she said.

PK OK

Pharmacokinetic (PK) analyses may also be helpful in transitioning patients to EHL products.

To test patient responses to new products, her center tests patients for recovery from 15 minutes to 1 hour post-infusion, which will provide information about how the patient may respond to the product during a bleeding episode.

If the patient is on prophylaxis they will evaluate trough effectiveness to determine that patient’s responsiveness at the lowest level prior to the next infusion. Testing at other time points may be required based on the patient’s individual clinical history.

Center staff talk with each patient to discuss his needs and capabilities. If the patient is currently being managed with on-demand therapy, the talk may center on obstacles to utilization of prophylaxis and the patient’s desired infusion interval.

For patients currently on prophylaxis, they discuss the current regimen frequency and dose and assess how well it’s working. Staff members also provide information about alternative approaches to therapy, and ask patients specifically about their activity levels and dates of activity, compared with currently scheduled infusion days.

Patients are also educated about the reconstitution requirements for the new product, and are told to use up any remaining concentrates before switching over to the new product.

“As we move forward, within 2 to 4 weeks of starting a new therapy, we like to obtain a trough to see how their prophylaxis is working. At that time we ask how have you been doing on the new product, are you having any breakthrough bleeding, and how are you feeling about it,” Ms. Maahs said.

Weekly phone calls to the patient during the first month are also very helpful for reinforcing information about dosing regimens for bleeding episodes, reminding patients to call in if they experience a lead, and encouraging them to keep a treatment log. The phone call can also be helpful in identifying potential product-related reactions or other issues, she said.

‘Big impact’

“What’s the impact that we’ve seen? With factor IX, it has been really big. Previous on-demand patients have agreed that, ‘gosh, I’m infusing a couple of times a month anyway,’ so starting an every 14-day prophylactic regimen seems pretty reasonable,” she said.

“We’ve had infusion schedules in children change from twice weekly to once weekly and that has really decreased the burden of disease,” she added.

A few adults, however, have gone back to standard half-life products because of concerns that they would not be able to infuse when they thought they needed treatment, she noted.

The impact of the EHL factor VIII products has been smaller, although it has allowed slight increases in the dosing intervals (from every other day to every third day in children, for example), and has overall decreased the average number of monthly infusions from about 15 to about 10.

Some adolescents and young adults, who often have been on prophylaxis for all of their lives, have experienced absent or only minimal joint disease, and some have been able to extend their dosing intervals from every 4 to every 5 to 7 days, she said.

Ms. Maahs disclosed serving on advisory committees to Baxalta, Novo Nordisk, Biogen, Genentech, and CSL, and receiving honoraria related to those activities.

ORLANDO – Transitioning patients with hemophilia from standard clotting factor concentrates to newer extended half-life products takes planning, education, and a little patience, but the payoff can be better hemostasis, a hemophilia treatment specialist said.

“Real-world experience shows us that you can maintain effective protection with less infusion with these new products, but we also know that each person should be evaluated individually when determining what their specific optimal treatment is,” said Jennifer Maahs, a hemophilia nurse practitioner at the Indiana Hemophilia and Thrombosis Center in Indianapolis.

Staff and patient education about the proper use of newer extended half-life (EHL) products is the key to success, she added in an oral session at the World Federation of Hemophilia World Congress.

The new EHL products allow for longer intervals between doses, especially with EHL recombinant factor IX used to treat hemophilia B. Prophylaxis with standard factor IX concentrates requires doses of 25-40 IU/kg twice weekly; in contrasts, EHL products can be given in various doses based on patient responses of either 50 IU/kg every 7 days, 100 IU/kg every 10 days, 25-40 IU/kg every 7 days, or 50-75 IU/kg every 14 days.

In general, the longer intervals between dosing occur in adults; young children tend to require more frequent dosing and have lower levels of factor recovery, she noted.

Extended Experience

Her center currently has more than 100 patients maintained on prolonged half-life factor VIII and factor IX products.

“We have really learned a lot of lessons along the way, and we have had to modify our approach based on these lessons,” she said. “Each patient situation is unique, and everything needs to be individualized.”

Staff review the published literature to educate themselves on the EHL products and prepare answers to expected questions from patients. Ms. Maahs suggested identifying key staff who are best equipped to answer specific questions.

“From a patient standpoint, we’ve developed a patient notification letter, so for any new product that comes out – for example a new factor VIII product – the notification gets sent out factor VIII patients, and we do that for every new product that comes out,” she said.

PK OK

Pharmacokinetic (PK) analyses may also be helpful in transitioning patients to EHL products.

To test patient responses to new products, her center tests patients for recovery from 15 minutes to 1 hour post-infusion, which will provide information about how the patient may respond to the product during a bleeding episode.

If the patient is on prophylaxis they will evaluate trough effectiveness to determine that patient’s responsiveness at the lowest level prior to the next infusion. Testing at other time points may be required based on the patient’s individual clinical history.

Center staff talk with each patient to discuss his needs and capabilities. If the patient is currently being managed with on-demand therapy, the talk may center on obstacles to utilization of prophylaxis and the patient’s desired infusion interval.

For patients currently on prophylaxis, they discuss the current regimen frequency and dose and assess how well it’s working. Staff members also provide information about alternative approaches to therapy, and ask patients specifically about their activity levels and dates of activity, compared with currently scheduled infusion days.

Patients are also educated about the reconstitution requirements for the new product, and are told to use up any remaining concentrates before switching over to the new product.

“As we move forward, within 2 to 4 weeks of starting a new therapy, we like to obtain a trough to see how their prophylaxis is working. At that time we ask how have you been doing on the new product, are you having any breakthrough bleeding, and how are you feeling about it,” Ms. Maahs said.

Weekly phone calls to the patient during the first month are also very helpful for reinforcing information about dosing regimens for bleeding episodes, reminding patients to call in if they experience a lead, and encouraging them to keep a treatment log. The phone call can also be helpful in identifying potential product-related reactions or other issues, she said.

‘Big impact’

“What’s the impact that we’ve seen? With factor IX, it has been really big. Previous on-demand patients have agreed that, ‘gosh, I’m infusing a couple of times a month anyway,’ so starting an every 14-day prophylactic regimen seems pretty reasonable,” she said.

“We’ve had infusion schedules in children change from twice weekly to once weekly and that has really decreased the burden of disease,” she added.

A few adults, however, have gone back to standard half-life products because of concerns that they would not be able to infuse when they thought they needed treatment, she noted.

The impact of the EHL factor VIII products has been smaller, although it has allowed slight increases in the dosing intervals (from every other day to every third day in children, for example), and has overall decreased the average number of monthly infusions from about 15 to about 10.

Some adolescents and young adults, who often have been on prophylaxis for all of their lives, have experienced absent or only minimal joint disease, and some have been able to extend their dosing intervals from every 4 to every 5 to 7 days, she said.

Ms. Maahs disclosed serving on advisory committees to Baxalta, Novo Nordisk, Biogen, Genentech, and CSL, and receiving honoraria related to those activities.

Editor in Chief:

John I. Allen, MD, MBA, AGAF

In 1980, Dr. Allen completed training at the University of Minnesota, Minneapolis, and then spent 10 years on their faculty. In 1991, he joined a private gastroenterology practice in Minneapolis and helped build this single-specialty GI practice into Minnesota Gastroenterology, one of the largest GI practices in the country. In 2013, he left practice to become clinical chief of digestive diseases and professor of medicine at Yale University School of Medicine. In September, 2016, he joined the faculty at the University of Michigan Medical Center, Ann Arbor. He currently remains on the Board of Directors of Allina Health, a large integrated health system in Minnesota.

Dr. Allen has served the American Gastroenterological Association (AGA) in multiple roles. He chaired the Clinical Practice Committee and led development of most quality measures currently in Medicare’s value-based payment system. Dr. Allen serves on the GI Specialty Board of the American Board of Internal Medicine and from May 2014 until May 2015, was president of the AGA Institute.

Associate Editors:

Megan A. Adams, MD, JD, MSc

Dr. Adams is a general gastroenterologist at the Ann Arbor VA and investigator in the VA Ann Arbor Center for Clinical Management Research, with an academic appointment as a clinical lecturer in the division of gastroenterology at the University of Michigan. As a gastroenterologist, attorney, and health services/policy researcher, her primary area of interest lies in improving GI health care delivery. Her current work focuses on improving our understanding of the drivers of inappropriate use of endoscopic resources in order to devise mechanisms to deliver higher-value care. She also has expertise in medicolegal issues in gastroenterology, as well as patient safety and quality improvement. She has served various roles in the AGA over the past 4 years, including as a previous member of the Trainee and Young GI Committee and Future Leaders Program Advisory Board. She currently serves as chair-elect of the AGA Quality Measures Committee.

Ziad F. Gellad, MD, MPH

Dr. Gellad is an associate professor of medicine in the division of gastroenterology at Duke University Medical Center, Durham, N.C., and a faculty member of the Duke Clinical Research Institute. He is also a VA Career Development Awardee and holds an appointment in the Health Services Research and Development Center of Innovation at the Durham VA Medical Center. Dr. Gellad received his MD and MPH degrees from Johns Hopkins University. He completed a residency in internal medicine and a fellowship in gastroenterology at Duke University Medical Center. Dr. Gellad’s research is focused on the implementation of systems engineering methods, including discrete event simulation, to improve the value of health care delivery. He is the director of quality for the division of gastroenterology and director of clinical improvement for the department of medicine at Duke University Medical Center. He also serves as chair of the AGA Quality Measures Committee.

Kim L. Isaacs, MD, PhD, AGAF

Dr. Isaacs is professor of medicine in the division of gastroenterology and hepatology at the University of North Carolina at Chapel Hill. She is codirector of the UNC Center for Inflammatory Bowel Disease and associate program director of the gastroenterology fellowship program at the university. She received her MD and PhD at the State University of New York at Stony Brook and completed her internship, residency, and fellowship in gastroenterology at the University of North Carolina at Chapel Hill. She is active in the clinical care of patients with inflammatory bowel disease and is an investigator in numerous clinical studies in the management and treatment of gastrointestinal disorders including ulcerative colitis, pouchitis, and Crohn’s disease. She has served on the AGA’s constitution and bylaws committee and the Education and Training Committee.

Gyanprakash A. Ketwaroo MD, MSc

Dr. Ketwaroo is an assistant professor in the division of gastroenterology and hepatology at Baylor College of Medicine, Houston, and an advanced endoscopist at the Michael E. Debakey VA Medical Center in Houston. After graduating with a degree in chemical physics from Brown University, he studied at Oxford University on a Rhodes Scholarship. He attended Harvard Medical School and completed an internal medicine residency at the Massachusetts General Hospital. This was followed by gastroenterology and advanced endoscopy fellowship training at the Beth Israel Deaconess Medical Center. He is chair of the AGA Trainee and Young GI Committee. His research interests include Barrett’s esophagus, chronic pancreatitis, and advanced imaging of gastrointestinal disease.

Lawrence R. Kosinski, MD, MBA, AGAF, FACG

Dr. Kosinski has been in the practice of gastroenterology since 1984. He received his MD from Loyola University Chicago Stritch School of Medicine in 1978 and earned his MBA from Northwestern University Kellogg School of Management in 1998. He is currently one of the managing partners of the Illinois Gastroenterology Group (IGG), the largest gastroenterology practice in Illinois.

In addition to his medical practice, Dr. Kosinski is the Clinical Private Practice Councilor for the American Gastroenterological Association and serves on its Governing Board. Locally, he is a member of the Advocate Sherman Hospital Board of Directors, Elgin, Ill.

In January 2014, Dr. Kosinski started SonarMD, a technology company formed to bring the success of Project Sonar to a national presence. He serves as its president and chief medical officer.

Sonia S. Kupfer, MD

Dr. Kupfer is an adult gastroenterologist with clinical and research interests in the genetics of gastrointestinal diseases. She is an assistant professor in the section of gastroenterology and serves as director of the Gastrointestinal Cancer Risk and Prevention Clinic at the University of Chicago. She is also a member of the University of Chicago Celiac Disease Center. She graduated from Yale University and completed her medical training including chief residency and gastroenterology fellowship at the University of Chicago. She received an F32 individual training grant and an NCI K08 career development award to study colorectal cancer genetics in African Americans. She is site primary investigator on a number of National Institutes of Health–sponsored clinical trials in colorectal cancer chemoprevention and screening. She served as codirector of two national clinical cancer genetics conferences and is a core faculty member in the City of Hope cancer genetics educational program. Dr. Kupfer is active on several AGA committees and is president-elect of the Collaborative Group of the Americas on Inherited Colorectal Cancer. She has mentored numerous medical students, residents, and fellows and teaches in the medical school.

Wajahat Mehal, MD, DPhil

Dr. Mehal is a hepatologist and director of the Yale Weight Loss Program at Yale University, New Haven, Conn. He obtained his medical training and DPhil at the University of Oxford, and completed his residency, chief residency, and Howard Hughes postdoctoral fellowship at Yale University. He has an active research group working in the area of sterile liver inflammation which covers alcoholic and nonalcoholic steatohepatitis. His clinical training is in transplant hepatology, obesity medicine, and endobariatrics. His laboratory training is in immunobiology and liver fibrosis. He has published widely in areas of inflammation and liver disease.

Editor in Chief:

John I. Allen, MD, MBA, AGAF

In 1980, Dr. Allen completed training at the University of Minnesota, Minneapolis, and then spent 10 years on their faculty. In 1991, he joined a private gastroenterology practice in Minneapolis and helped build this single-specialty GI practice into Minnesota Gastroenterology, one of the largest GI practices in the country. In 2013, he left practice to become clinical chief of digestive diseases and professor of medicine at Yale University School of Medicine. In September, 2016, he joined the faculty at the University of Michigan Medical Center, Ann Arbor. He currently remains on the Board of Directors of Allina Health, a large integrated health system in Minnesota.

Dr. Allen has served the American Gastroenterological Association (AGA) in multiple roles. He chaired the Clinical Practice Committee and led development of most quality measures currently in Medicare’s value-based payment system. Dr. Allen serves on the GI Specialty Board of the American Board of Internal Medicine and from May 2014 until May 2015, was president of the AGA Institute.

Associate Editors:

Megan A. Adams, MD, JD, MSc

Dr. Adams is a general gastroenterologist at the Ann Arbor VA and investigator in the VA Ann Arbor Center for Clinical Management Research, with an academic appointment as a clinical lecturer in the division of gastroenterology at the University of Michigan. As a gastroenterologist, attorney, and health services/policy researcher, her primary area of interest lies in improving GI health care delivery. Her current work focuses on improving our understanding of the drivers of inappropriate use of endoscopic resources in order to devise mechanisms to deliver higher-value care. She also has expertise in medicolegal issues in gastroenterology, as well as patient safety and quality improvement. She has served various roles in the AGA over the past 4 years, including as a previous member of the Trainee and Young GI Committee and Future Leaders Program Advisory Board. She currently serves as chair-elect of the AGA Quality Measures Committee.

Ziad F. Gellad, MD, MPH

Dr. Gellad is an associate professor of medicine in the division of gastroenterology at Duke University Medical Center, Durham, N.C., and a faculty member of the Duke Clinical Research Institute. He is also a VA Career Development Awardee and holds an appointment in the Health Services Research and Development Center of Innovation at the Durham VA Medical Center. Dr. Gellad received his MD and MPH degrees from Johns Hopkins University. He completed a residency in internal medicine and a fellowship in gastroenterology at Duke University Medical Center. Dr. Gellad’s research is focused on the implementation of systems engineering methods, including discrete event simulation, to improve the value of health care delivery. He is the director of quality for the division of gastroenterology and director of clinical improvement for the department of medicine at Duke University Medical Center. He also serves as chair of the AGA Quality Measures Committee.

Kim L. Isaacs, MD, PhD, AGAF

Dr. Isaacs is professor of medicine in the division of gastroenterology and hepatology at the University of North Carolina at Chapel Hill. She is codirector of the UNC Center for Inflammatory Bowel Disease and associate program director of the gastroenterology fellowship program at the university. She received her MD and PhD at the State University of New York at Stony Brook and completed her internship, residency, and fellowship in gastroenterology at the University of North Carolina at Chapel Hill. She is active in the clinical care of patients with inflammatory bowel disease and is an investigator in numerous clinical studies in the management and treatment of gastrointestinal disorders including ulcerative colitis, pouchitis, and Crohn’s disease. She has served on the AGA’s constitution and bylaws committee and the Education and Training Committee.

Gyanprakash A. Ketwaroo MD, MSc

Dr. Ketwaroo is an assistant professor in the division of gastroenterology and hepatology at Baylor College of Medicine, Houston, and an advanced endoscopist at the Michael E. Debakey VA Medical Center in Houston. After graduating with a degree in chemical physics from Brown University, he studied at Oxford University on a Rhodes Scholarship. He attended Harvard Medical School and completed an internal medicine residency at the Massachusetts General Hospital. This was followed by gastroenterology and advanced endoscopy fellowship training at the Beth Israel Deaconess Medical Center. He is chair of the AGA Trainee and Young GI Committee. His research interests include Barrett’s esophagus, chronic pancreatitis, and advanced imaging of gastrointestinal disease.

Lawrence R. Kosinski, MD, MBA, AGAF, FACG

Dr. Kosinski has been in the practice of gastroenterology since 1984. He received his MD from Loyola University Chicago Stritch School of Medicine in 1978 and earned his MBA from Northwestern University Kellogg School of Management in 1998. He is currently one of the managing partners of the Illinois Gastroenterology Group (IGG), the largest gastroenterology practice in Illinois.

In addition to his medical practice, Dr. Kosinski is the Clinical Private Practice Councilor for the American Gastroenterological Association and serves on its Governing Board. Locally, he is a member of the Advocate Sherman Hospital Board of Directors, Elgin, Ill.

In January 2014, Dr. Kosinski started SonarMD, a technology company formed to bring the success of Project Sonar to a national presence. He serves as its president and chief medical officer.

Sonia S. Kupfer, MD

Dr. Kupfer is an adult gastroenterologist with clinical and research interests in the genetics of gastrointestinal diseases. She is an assistant professor in the section of gastroenterology and serves as director of the Gastrointestinal Cancer Risk and Prevention Clinic at the University of Chicago. She is also a member of the University of Chicago Celiac Disease Center. She graduated from Yale University and completed her medical training including chief residency and gastroenterology fellowship at the University of Chicago. She received an F32 individual training grant and an NCI K08 career development award to study colorectal cancer genetics in African Americans. She is site primary investigator on a number of National Institutes of Health–sponsored clinical trials in colorectal cancer chemoprevention and screening. She served as codirector of two national clinical cancer genetics conferences and is a core faculty member in the City of Hope cancer genetics educational program. Dr. Kupfer is active on several AGA committees and is president-elect of the Collaborative Group of the Americas on Inherited Colorectal Cancer. She has mentored numerous medical students, residents, and fellows and teaches in the medical school.

Wajahat Mehal, MD, DPhil

Dr. Mehal is a hepatologist and director of the Yale Weight Loss Program at Yale University, New Haven, Conn. He obtained his medical training and DPhil at the University of Oxford, and completed his residency, chief residency, and Howard Hughes postdoctoral fellowship at Yale University. He has an active research group working in the area of sterile liver inflammation which covers alcoholic and nonalcoholic steatohepatitis. His clinical training is in transplant hepatology, obesity medicine, and endobariatrics. His laboratory training is in immunobiology and liver fibrosis. He has published widely in areas of inflammation and liver disease.

Editor in Chief:

John I. Allen, MD, MBA, AGAF

In 1980, Dr. Allen completed training at the University of Minnesota, Minneapolis, and then spent 10 years on their faculty. In 1991, he joined a private gastroenterology practice in Minneapolis and helped build this single-specialty GI practice into Minnesota Gastroenterology, one of the largest GI practices in the country. In 2013, he left practice to become clinical chief of digestive diseases and professor of medicine at Yale University School of Medicine. In September, 2016, he joined the faculty at the University of Michigan Medical Center, Ann Arbor. He currently remains on the Board of Directors of Allina Health, a large integrated health system in Minnesota.

Dr. Allen has served the American Gastroenterological Association (AGA) in multiple roles. He chaired the Clinical Practice Committee and led development of most quality measures currently in Medicare’s value-based payment system. Dr. Allen serves on the GI Specialty Board of the American Board of Internal Medicine and from May 2014 until May 2015, was president of the AGA Institute.

Associate Editors:

Megan A. Adams, MD, JD, MSc

Dr. Adams is a general gastroenterologist at the Ann Arbor VA and investigator in the VA Ann Arbor Center for Clinical Management Research, with an academic appointment as a clinical lecturer in the division of gastroenterology at the University of Michigan. As a gastroenterologist, attorney, and health services/policy researcher, her primary area of interest lies in improving GI health care delivery. Her current work focuses on improving our understanding of the drivers of inappropriate use of endoscopic resources in order to devise mechanisms to deliver higher-value care. She also has expertise in medicolegal issues in gastroenterology, as well as patient safety and quality improvement. She has served various roles in the AGA over the past 4 years, including as a previous member of the Trainee and Young GI Committee and Future Leaders Program Advisory Board. She currently serves as chair-elect of the AGA Quality Measures Committee.

Ziad F. Gellad, MD, MPH

Dr. Gellad is an associate professor of medicine in the division of gastroenterology at Duke University Medical Center, Durham, N.C., and a faculty member of the Duke Clinical Research Institute. He is also a VA Career Development Awardee and holds an appointment in the Health Services Research and Development Center of Innovation at the Durham VA Medical Center. Dr. Gellad received his MD and MPH degrees from Johns Hopkins University. He completed a residency in internal medicine and a fellowship in gastroenterology at Duke University Medical Center. Dr. Gellad’s research is focused on the implementation of systems engineering methods, including discrete event simulation, to improve the value of health care delivery. He is the director of quality for the division of gastroenterology and director of clinical improvement for the department of medicine at Duke University Medical Center. He also serves as chair of the AGA Quality Measures Committee.

Kim L. Isaacs, MD, PhD, AGAF

Dr. Isaacs is professor of medicine in the division of gastroenterology and hepatology at the University of North Carolina at Chapel Hill. She is codirector of the UNC Center for Inflammatory Bowel Disease and associate program director of the gastroenterology fellowship program at the university. She received her MD and PhD at the State University of New York at Stony Brook and completed her internship, residency, and fellowship in gastroenterology at the University of North Carolina at Chapel Hill. She is active in the clinical care of patients with inflammatory bowel disease and is an investigator in numerous clinical studies in the management and treatment of gastrointestinal disorders including ulcerative colitis, pouchitis, and Crohn’s disease. She has served on the AGA’s constitution and bylaws committee and the Education and Training Committee.

Gyanprakash A. Ketwaroo MD, MSc

Dr. Ketwaroo is an assistant professor in the division of gastroenterology and hepatology at Baylor College of Medicine, Houston, and an advanced endoscopist at the Michael E. Debakey VA Medical Center in Houston. After graduating with a degree in chemical physics from Brown University, he studied at Oxford University on a Rhodes Scholarship. He attended Harvard Medical School and completed an internal medicine residency at the Massachusetts General Hospital. This was followed by gastroenterology and advanced endoscopy fellowship training at the Beth Israel Deaconess Medical Center. He is chair of the AGA Trainee and Young GI Committee. His research interests include Barrett’s esophagus, chronic pancreatitis, and advanced imaging of gastrointestinal disease.

Lawrence R. Kosinski, MD, MBA, AGAF, FACG

Dr. Kosinski has been in the practice of gastroenterology since 1984. He received his MD from Loyola University Chicago Stritch School of Medicine in 1978 and earned his MBA from Northwestern University Kellogg School of Management in 1998. He is currently one of the managing partners of the Illinois Gastroenterology Group (IGG), the largest gastroenterology practice in Illinois.

In addition to his medical practice, Dr. Kosinski is the Clinical Private Practice Councilor for the American Gastroenterological Association and serves on its Governing Board. Locally, he is a member of the Advocate Sherman Hospital Board of Directors, Elgin, Ill.

In January 2014, Dr. Kosinski started SonarMD, a technology company formed to bring the success of Project Sonar to a national presence. He serves as its president and chief medical officer.

Sonia S. Kupfer, MD

Dr. Kupfer is an adult gastroenterologist with clinical and research interests in the genetics of gastrointestinal diseases. She is an assistant professor in the section of gastroenterology and serves as director of the Gastrointestinal Cancer Risk and Prevention Clinic at the University of Chicago. She is also a member of the University of Chicago Celiac Disease Center. She graduated from Yale University and completed her medical training including chief residency and gastroenterology fellowship at the University of Chicago. She received an F32 individual training grant and an NCI K08 career development award to study colorectal cancer genetics in African Americans. She is site primary investigator on a number of National Institutes of Health–sponsored clinical trials in colorectal cancer chemoprevention and screening. She served as codirector of two national clinical cancer genetics conferences and is a core faculty member in the City of Hope cancer genetics educational program. Dr. Kupfer is active on several AGA committees and is president-elect of the Collaborative Group of the Americas on Inherited Colorectal Cancer. She has mentored numerous medical students, residents, and fellows and teaches in the medical school.

Wajahat Mehal, MD, DPhil

Dr. Mehal is a hepatologist and director of the Yale Weight Loss Program at Yale University, New Haven, Conn. He obtained his medical training and DPhil at the University of Oxford, and completed his residency, chief residency, and Howard Hughes postdoctoral fellowship at Yale University. He has an active research group working in the area of sterile liver inflammation which covers alcoholic and nonalcoholic steatohepatitis. His clinical training is in transplant hepatology, obesity medicine, and endobariatrics. His laboratory training is in immunobiology and liver fibrosis. He has published widely in areas of inflammation and liver disease.

Treatment recommendations for Waldenström macroglobulinemia have been updated based on the advice of a task force convened at the Eighth International Workshop on Waldenström Macroglobulinemia; the guidelines have been published in Blood.

The task force was impaneled to review recently published and ongoing clinical trial data as well as the impact of the newly recognized mutations MYD88 and CXCR4 on treatment decisions, indications for B-cell receptor and proteasome inhibitors, and future clinical trial initiatives.

Michail Charakidis, David Joseph Russell/Wikimedia Commons/CC BY 2.0

The panel reiterated that the criteria for initiating therapy include immunoglobulin M (IgM)-related complications and/or symptoms that are related to direct involvement of the bone marrow by tumor cells, constitutional symptoms, and bulky extramedullary disease. Patients presenting with symptoms that include symptomatic hyperviscosity, moderate to severe hemolytic anemia, and symptomatic cryoglobulinemia need immediate treatment.

Close observation is recommended for the subgroup of patients who do not really fulfill the criteria for a diagnosis of Waldenström macroglobulinemia (WM), and whose laboratory findings may be the only indicator of the presence of a progressive disease.

Treatment recommendations

For symptomatic patients in the first-line setting, “anti-CD20 monoclonal antibody therapy alone or in combination with chemotherapy is an important standard of care for most patients with WM,” the authors, led by Veronique Leblond, MD, of Pitié-Salpêtrière Hôpital, Paris, wrote.

Rituximab is frequently used in WM, either as monotherapy or in combination with chemotherapeutic agents. The panel cautions that rituximab as monotherapy should be avoided in patients with high IgM levels, because of a lower chance of response and the risk of an IgM flare.

In patients with high IgM levels (typically around 4,000 mg/dL), plasmapheresis can be initiated before rituximab therapy, and plasmapheresis should always and immediately be used when symptomatic hyperviscosity is present. However, plasmapheresis alone is not an effective treatment for WM and must be followed by a rapidly acting cytoreductive regimen.

Several rituximab combinations are recommended by the panel. These include:

• Dexamethasone-rituximab-cyclophosphamide, which is an active and safe option, has a manageable toxicity, and can be considered for frail patients who need combination therapy.

• Bendamustine-rituximab is effective for front-line treatment and is well tolerated even in elderly patients who experience limited episodes of myelosuppression and infections.

Other therapeutic regimens include bortezomib-based therapy, which is recommended for patients with high IgM levels, symptomatic hyperviscosity, cryoglobulinemia or cold agglutinemia, amyloidosis, and renal impairment or in young patients who prefer to avoid alkylator or nucleoside analogue therapy.

Another option is carfilzomib-based therapy, which is an emerging “neuropathy-sparing” regimen for proteasome-inhibitor–based therapy, although it may not be the best choice for elderly patients with preexisting cardiac conditions due to potential cardiac toxicity.

Ibrutinib has been approved as a primary therapy for patients who are not candidates for chemoimmunotherapy, but the authors point out that the optimal use of this agent is still being investigated.

“The aim of the first-line treatments is to reach a high response rate with a prolonged progression-free survival,” write the authors. “The panel agrees that there is need to perform clinical trials with chemotherapy-free combinations with new compounds alone or in combination with anti-CD20 antibodies.”

For symptomatic previously treated patients

The panel also offered recommendations for previously treated symptomatic patients who have relapsed or are refractory to treatment.

Any of the interventions recommended for symptomatic, untreated patients can be considered for those who have already gone through first line therapy. Retreatment can be considered with a specific intervention if a response was achieved for 2 or more years with that therapy, although they caution that patients who have progressed on first-line ibrutinib should not use it again.

Ofatumumab is a potential option for patients who are unable to tolerate rituximab, and nucleoside analogues can be considered in fit patients who have not responded to less-toxic treatments.

Another option in this setting is everolimus, although since it is associated with considerable toxicities, the best candidates for this drug are those who have not responded to or have progressed after multiple lines of other better-tolerated regimens.

Immunomodulatory agents can also be considered, but in the context of a clinical trial only, because of their potential adverse events.

Finally, the panel also agreed that stem cell transplantation should be discussed with select patients, and while it is a feasible and effective treatment option for high-risk WM patients, it should be ideally offered at early relapse.

Investigating B-cell receptor (BCR) pathway inhibitors along with existing and novel compounds in patients in the relapsed/refractory setting should be a priority, according to the panel.

“BCR inhibitors, combined with proteasome inhibitors, would be of interest for overcoming resistance by interfering with the two key pathways that are affected by MYD88,” wrote Dr. Leblond and coauthors.

Treatment recommendations for Waldenström macroglobulinemia have been updated based on the advice of a task force convened at the Eighth International Workshop on Waldenström Macroglobulinemia; the guidelines have been published in Blood.

The task force was impaneled to review recently published and ongoing clinical trial data as well as the impact of the newly recognized mutations MYD88 and CXCR4 on treatment decisions, indications for B-cell receptor and proteasome inhibitors, and future clinical trial initiatives.

Michail Charakidis, David Joseph Russell/Wikimedia Commons/CC BY 2.0

The panel reiterated that the criteria for initiating therapy include immunoglobulin M (IgM)-related complications and/or symptoms that are related to direct involvement of the bone marrow by tumor cells, constitutional symptoms, and bulky extramedullary disease. Patients presenting with symptoms that include symptomatic hyperviscosity, moderate to severe hemolytic anemia, and symptomatic cryoglobulinemia need immediate treatment.

Close observation is recommended for the subgroup of patients who do not really fulfill the criteria for a diagnosis of Waldenström macroglobulinemia (WM), and whose laboratory findings may be the only indicator of the presence of a progressive disease.

Treatment recommendations

For symptomatic patients in the first-line setting, “anti-CD20 monoclonal antibody therapy alone or in combination with chemotherapy is an important standard of care for most patients with WM,” the authors, led by Veronique Leblond, MD, of Pitié-Salpêtrière Hôpital, Paris, wrote.

Rituximab is frequently used in WM, either as monotherapy or in combination with chemotherapeutic agents. The panel cautions that rituximab as monotherapy should be avoided in patients with high IgM levels, because of a lower chance of response and the risk of an IgM flare.

In patients with high IgM levels (typically around 4,000 mg/dL), plasmapheresis can be initiated before rituximab therapy, and plasmapheresis should always and immediately be used when symptomatic hyperviscosity is present. However, plasmapheresis alone is not an effective treatment for WM and must be followed by a rapidly acting cytoreductive regimen.

Several rituximab combinations are recommended by the panel. These include:

• Dexamethasone-rituximab-cyclophosphamide, which is an active and safe option, has a manageable toxicity, and can be considered for frail patients who need combination therapy.

• Bendamustine-rituximab is effective for front-line treatment and is well tolerated even in elderly patients who experience limited episodes of myelosuppression and infections.

Other therapeutic regimens include bortezomib-based therapy, which is recommended for patients with high IgM levels, symptomatic hyperviscosity, cryoglobulinemia or cold agglutinemia, amyloidosis, and renal impairment or in young patients who prefer to avoid alkylator or nucleoside analogue therapy.

Another option is carfilzomib-based therapy, which is an emerging “neuropathy-sparing” regimen for proteasome-inhibitor–based therapy, although it may not be the best choice for elderly patients with preexisting cardiac conditions due to potential cardiac toxicity.

Ibrutinib has been approved as a primary therapy for patients who are not candidates for chemoimmunotherapy, but the authors point out that the optimal use of this agent is still being investigated.

“The aim of the first-line treatments is to reach a high response rate with a prolonged progression-free survival,” write the authors. “The panel agrees that there is need to perform clinical trials with chemotherapy-free combinations with new compounds alone or in combination with anti-CD20 antibodies.”

For symptomatic previously treated patients

The panel also offered recommendations for previously treated symptomatic patients who have relapsed or are refractory to treatment.

Any of the interventions recommended for symptomatic, untreated patients can be considered for those who have already gone through first line therapy. Retreatment can be considered with a specific intervention if a response was achieved for 2 or more years with that therapy, although they caution that patients who have progressed on first-line ibrutinib should not use it again.

Ofatumumab is a potential option for patients who are unable to tolerate rituximab, and nucleoside analogues can be considered in fit patients who have not responded to less-toxic treatments.

Another option in this setting is everolimus, although since it is associated with considerable toxicities, the best candidates for this drug are those who have not responded to or have progressed after multiple lines of other better-tolerated regimens.

Immunomodulatory agents can also be considered, but in the context of a clinical trial only, because of their potential adverse events.

Finally, the panel also agreed that stem cell transplantation should be discussed with select patients, and while it is a feasible and effective treatment option for high-risk WM patients, it should be ideally offered at early relapse.

Investigating B-cell receptor (BCR) pathway inhibitors along with existing and novel compounds in patients in the relapsed/refractory setting should be a priority, according to the panel.

“BCR inhibitors, combined with proteasome inhibitors, would be of interest for overcoming resistance by interfering with the two key pathways that are affected by MYD88,” wrote Dr. Leblond and coauthors.

Treatment recommendations for Waldenström macroglobulinemia have been updated based on the advice of a task force convened at the Eighth International Workshop on Waldenström Macroglobulinemia; the guidelines have been published in Blood.

The task force was impaneled to review recently published and ongoing clinical trial data as well as the impact of the newly recognized mutations MYD88 and CXCR4 on treatment decisions, indications for B-cell receptor and proteasome inhibitors, and future clinical trial initiatives.

Michail Charakidis, David Joseph Russell/Wikimedia Commons/CC BY 2.0

The panel reiterated that the criteria for initiating therapy include immunoglobulin M (IgM)-related complications and/or symptoms that are related to direct involvement of the bone marrow by tumor cells, constitutional symptoms, and bulky extramedullary disease. Patients presenting with symptoms that include symptomatic hyperviscosity, moderate to severe hemolytic anemia, and symptomatic cryoglobulinemia need immediate treatment.

Close observation is recommended for the subgroup of patients who do not really fulfill the criteria for a diagnosis of Waldenström macroglobulinemia (WM), and whose laboratory findings may be the only indicator of the presence of a progressive disease.

Treatment recommendations

For symptomatic patients in the first-line setting, “anti-CD20 monoclonal antibody therapy alone or in combination with chemotherapy is an important standard of care for most patients with WM,” the authors, led by Veronique Leblond, MD, of Pitié-Salpêtrière Hôpital, Paris, wrote.

Rituximab is frequently used in WM, either as monotherapy or in combination with chemotherapeutic agents. The panel cautions that rituximab as monotherapy should be avoided in patients with high IgM levels, because of a lower chance of response and the risk of an IgM flare.

In patients with high IgM levels (typically around 4,000 mg/dL), plasmapheresis can be initiated before rituximab therapy, and plasmapheresis should always and immediately be used when symptomatic hyperviscosity is present. However, plasmapheresis alone is not an effective treatment for WM and must be followed by a rapidly acting cytoreductive regimen.

Several rituximab combinations are recommended by the panel. These include:

• Dexamethasone-rituximab-cyclophosphamide, which is an active and safe option, has a manageable toxicity, and can be considered for frail patients who need combination therapy.

• Bendamustine-rituximab is effective for front-line treatment and is well tolerated even in elderly patients who experience limited episodes of myelosuppression and infections.

Other therapeutic regimens include bortezomib-based therapy, which is recommended for patients with high IgM levels, symptomatic hyperviscosity, cryoglobulinemia or cold agglutinemia, amyloidosis, and renal impairment or in young patients who prefer to avoid alkylator or nucleoside analogue therapy.

Another option is carfilzomib-based therapy, which is an emerging “neuropathy-sparing” regimen for proteasome-inhibitor–based therapy, although it may not be the best choice for elderly patients with preexisting cardiac conditions due to potential cardiac toxicity.

Ibrutinib has been approved as a primary therapy for patients who are not candidates for chemoimmunotherapy, but the authors point out that the optimal use of this agent is still being investigated.

“The aim of the first-line treatments is to reach a high response rate with a prolonged progression-free survival,” write the authors. “The panel agrees that there is need to perform clinical trials with chemotherapy-free combinations with new compounds alone or in combination with anti-CD20 antibodies.”

For symptomatic previously treated patients

The panel also offered recommendations for previously treated symptomatic patients who have relapsed or are refractory to treatment.

Any of the interventions recommended for symptomatic, untreated patients can be considered for those who have already gone through first line therapy. Retreatment can be considered with a specific intervention if a response was achieved for 2 or more years with that therapy, although they caution that patients who have progressed on first-line ibrutinib should not use it again.

Ofatumumab is a potential option for patients who are unable to tolerate rituximab, and nucleoside analogues can be considered in fit patients who have not responded to less-toxic treatments.

Another option in this setting is everolimus, although since it is associated with considerable toxicities, the best candidates for this drug are those who have not responded to or have progressed after multiple lines of other better-tolerated regimens.

Immunomodulatory agents can also be considered, but in the context of a clinical trial only, because of their potential adverse events.

Finally, the panel also agreed that stem cell transplantation should be discussed with select patients, and while it is a feasible and effective treatment option for high-risk WM patients, it should be ideally offered at early relapse.

Investigating B-cell receptor (BCR) pathway inhibitors along with existing and novel compounds in patients in the relapsed/refractory setting should be a priority, according to the panel.

“BCR inhibitors, combined with proteasome inhibitors, would be of interest for overcoming resistance by interfering with the two key pathways that are affected by MYD88,” wrote Dr. Leblond and coauthors.

The U.S Food and Drug Administration provided 510(k) clearance for the new Aer-O-Scope colonoscope system, according to GI View of Ramat Gan, Israel.

The Aer-O-Scope is a self-propelled, disposable colonoscope with a 360-degree view of the colon that is controlled with a joystick.

The new system, which is an improvement on the earlier Aer-O-Scope colonoscope, also FDA approved, will have two working channels in order to provide therapeutic access for standard tools to take biopsies or perform polypectomies. It uses a soft multilumen tube designed to significantly reduce pressure on the colon wall, which may increase patient safety. It is also hydrophilic and reduces the friction between bowel and scope by more than 90%. The system has a self-propelled intubation process, created with balloons and low pressure CO₂ gas. And, like all colonoscopes, the Aer-O-Scope provides insufflation, irrigation, and suction.

“The new Aer-O-Scope system with therapeutic access has many significant clinical benefits including enabling physicians to more easily, effectively, and efficiently identify and remove polyps and prevent colon cancer,” said GI View CEO Tal Simchony, PhD, in a press release. “We are now working on U.S. market introduction of the Aer-O-Scope. Postmarket studies are also in the plans.”

Colorectal cancer is one of the biggest causes of cancer death worldwide. It can be prevented by early detection and removal of polyps. Read more about Aer-O-Scope on GI View’s website.

[email protected]

The U.S Food and Drug Administration provided 510(k) clearance for the new Aer-O-Scope colonoscope system, according to GI View of Ramat Gan, Israel.

The Aer-O-Scope is a self-propelled, disposable colonoscope with a 360-degree view of the colon that is controlled with a joystick.

The new system, which is an improvement on the earlier Aer-O-Scope colonoscope, also FDA approved, will have two working channels in order to provide therapeutic access for standard tools to take biopsies or perform polypectomies. It uses a soft multilumen tube designed to significantly reduce pressure on the colon wall, which may increase patient safety. It is also hydrophilic and reduces the friction between bowel and scope by more than 90%. The system has a self-propelled intubation process, created with balloons and low pressure CO₂ gas. And, like all colonoscopes, the Aer-O-Scope provides insufflation, irrigation, and suction.

“The new Aer-O-Scope system with therapeutic access has many significant clinical benefits including enabling physicians to more easily, effectively, and efficiently identify and remove polyps and prevent colon cancer,” said GI View CEO Tal Simchony, PhD, in a press release. “We are now working on U.S. market introduction of the Aer-O-Scope. Postmarket studies are also in the plans.”

Colorectal cancer is one of the biggest causes of cancer death worldwide. It can be prevented by early detection and removal of polyps. Read more about Aer-O-Scope on GI View’s website.

[email protected]

The U.S Food and Drug Administration provided 510(k) clearance for the new Aer-O-Scope colonoscope system, according to GI View of Ramat Gan, Israel.

The Aer-O-Scope is a self-propelled, disposable colonoscope with a 360-degree view of the colon that is controlled with a joystick.

The new system, which is an improvement on the earlier Aer-O-Scope colonoscope, also FDA approved, will have two working channels in order to provide therapeutic access for standard tools to take biopsies or perform polypectomies. It uses a soft multilumen tube designed to significantly reduce pressure on the colon wall, which may increase patient safety. It is also hydrophilic and reduces the friction between bowel and scope by more than 90%. The system has a self-propelled intubation process, created with balloons and low pressure CO₂ gas. And, like all colonoscopes, the Aer-O-Scope provides insufflation, irrigation, and suction.

“The new Aer-O-Scope system with therapeutic access has many significant clinical benefits including enabling physicians to more easily, effectively, and efficiently identify and remove polyps and prevent colon cancer,” said GI View CEO Tal Simchony, PhD, in a press release. “We are now working on U.S. market introduction of the Aer-O-Scope. Postmarket studies are also in the plans.”

Colorectal cancer is one of the biggest causes of cancer death worldwide. It can be prevented by early detection and removal of polyps. Read more about Aer-O-Scope on GI View’s website.

[email protected]

A large uptick in DNA methylation occurs at the time of progression in patients with Philadelphia chromosome–positive chronic myeloid leukemia (CML), according to results from a comparative cohort study. The observation raises the possibility of new therapeutic targets for advanced disease.

Researchers led by Gerwin Heller, PhD, of the Medical University of Vienna’s Clinical Division of Oncology and Comprehensive Cancer Center, Austria, collected peripheral blood mononuclear cells from 23 patients with CML during various disease phases (chronic phase in 17, acute phase in 5, and blast crisis in 9) and from 5 healthy controls.

©Zffoto/Thinkstock

They isolated DNA and analyzed it with a novel next-generation sequencing approach, known as reduced representation bisulfite sequencing, to identify the presence and extent of methylation.

Compared with the healthy controls, patients in chronic-phase CML had 666 differentially methylated CpG (cytosine-phosphate-guanine) sites, whereas those in blast crisis had 6,912 differentially methylated CpG sites (Leukemia. 2016;30:1861-8). Some 44% of the former but 88% of the latter affected CpG sites showed increased methylation.

Among patients with chronic-phase CML who experienced progression to the accelerated phase or blast crisis, analyses identified between 344 and 897 genes that were methylated at the time of progression but had not been at the time of diagnosis.

RNA sequencing determined that many of these newly methylated genes showed downregulated expression in the samples collected during blast crisis, compared with those collected during chronic phase disease. These genes included some tumor suppressor genes (EPB41L3, PRDX2), regulators of cell proliferation (BCL11B, NDRG2, PID1), and regulators of drug metabolism (CYP1B1), among others.

Treatment of CML cells with the epigenetically active drugs azacitidine (a DNA methyltransferase inhibitor) and trichostatin A (a histone deacetylase inhibitor) led to re-expression of the CYP1B1 gene.

“Together, our results demonstrate that CpG site methylation clearly increases during CML progression and that it may provide a useful basis for revealing new targets of therapy in advanced CML,” wrote Dr. Heller and colleagues, who disclosed that one of them has received research grants from Novartis and Ariad.

“Our findings suggest that investigating the efficacy of [DNA methyltransferase inhibitors] in patients with progressed CML should be considered,” they said.

[email protected]

A large uptick in DNA methylation occurs at the time of progression in patients with Philadelphia chromosome–positive chronic myeloid leukemia (CML), according to results from a comparative cohort study. The observation raises the possibility of new therapeutic targets for advanced disease.

Researchers led by Gerwin Heller, PhD, of the Medical University of Vienna’s Clinical Division of Oncology and Comprehensive Cancer Center, Austria, collected peripheral blood mononuclear cells from 23 patients with CML during various disease phases (chronic phase in 17, acute phase in 5, and blast crisis in 9) and from 5 healthy controls.

©Zffoto/Thinkstock

They isolated DNA and analyzed it with a novel next-generation sequencing approach, known as reduced representation bisulfite sequencing, to identify the presence and extent of methylation.

Compared with the healthy controls, patients in chronic-phase CML had 666 differentially methylated CpG (cytosine-phosphate-guanine) sites, whereas those in blast crisis had 6,912 differentially methylated CpG sites (Leukemia. 2016;30:1861-8). Some 44% of the former but 88% of the latter affected CpG sites showed increased methylation.

Among patients with chronic-phase CML who experienced progression to the accelerated phase or blast crisis, analyses identified between 344 and 897 genes that were methylated at the time of progression but had not been at the time of diagnosis.

RNA sequencing determined that many of these newly methylated genes showed downregulated expression in the samples collected during blast crisis, compared with those collected during chronic phase disease. These genes included some tumor suppressor genes (EPB41L3, PRDX2), regulators of cell proliferation (BCL11B, NDRG2, PID1), and regulators of drug metabolism (CYP1B1), among others.

Treatment of CML cells with the epigenetically active drugs azacitidine (a DNA methyltransferase inhibitor) and trichostatin A (a histone deacetylase inhibitor) led to re-expression of the CYP1B1 gene.

“Together, our results demonstrate that CpG site methylation clearly increases during CML progression and that it may provide a useful basis for revealing new targets of therapy in advanced CML,” wrote Dr. Heller and colleagues, who disclosed that one of them has received research grants from Novartis and Ariad.

“Our findings suggest that investigating the efficacy of [DNA methyltransferase inhibitors] in patients with progressed CML should be considered,” they said.

[email protected]

A large uptick in DNA methylation occurs at the time of progression in patients with Philadelphia chromosome–positive chronic myeloid leukemia (CML), according to results from a comparative cohort study. The observation raises the possibility of new therapeutic targets for advanced disease.

Researchers led by Gerwin Heller, PhD, of the Medical University of Vienna’s Clinical Division of Oncology and Comprehensive Cancer Center, Austria, collected peripheral blood mononuclear cells from 23 patients with CML during various disease phases (chronic phase in 17, acute phase in 5, and blast crisis in 9) and from 5 healthy controls.

©Zffoto/Thinkstock

They isolated DNA and analyzed it with a novel next-generation sequencing approach, known as reduced representation bisulfite sequencing, to identify the presence and extent of methylation.

Compared with the healthy controls, patients in chronic-phase CML had 666 differentially methylated CpG (cytosine-phosphate-guanine) sites, whereas those in blast crisis had 6,912 differentially methylated CpG sites (Leukemia. 2016;30:1861-8). Some 44% of the former but 88% of the latter affected CpG sites showed increased methylation.

Among patients with chronic-phase CML who experienced progression to the accelerated phase or blast crisis, analyses identified between 344 and 897 genes that were methylated at the time of progression but had not been at the time of diagnosis.

RNA sequencing determined that many of these newly methylated genes showed downregulated expression in the samples collected during blast crisis, compared with those collected during chronic phase disease. These genes included some tumor suppressor genes (EPB41L3, PRDX2), regulators of cell proliferation (BCL11B, NDRG2, PID1), and regulators of drug metabolism (CYP1B1), among others.

Treatment of CML cells with the epigenetically active drugs azacitidine (a DNA methyltransferase inhibitor) and trichostatin A (a histone deacetylase inhibitor) led to re-expression of the CYP1B1 gene.

“Together, our results demonstrate that CpG site methylation clearly increases during CML progression and that it may provide a useful basis for revealing new targets of therapy in advanced CML,” wrote Dr. Heller and colleagues, who disclosed that one of them has received research grants from Novartis and Ariad.

“Our findings suggest that investigating the efficacy of [DNA methyltransferase inhibitors] in patients with progressed CML should be considered,” they said.

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