CHICAGO – The investigational drug CPX-351 (Vyxeos) may become the new standard of care for older patients with secondary acute myeloid leukemia (AML), based on data presented at the annual meeting of the American Society of Clinical Oncology.

CPX-351 significantly improved overall survival, event-free survival, and treatment response without an increase in 60-day mortality or in the frequency and severity of adverse events as compared to the standard 7+3 regimen of cytarabine and daunorubicin.

In a video interview, primary investigator Dr. Jeffrey Lancet of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla., discusses the data to be presented to the Food and Drug Administration for approval of the drug, and why the liposomal formulation of cytarabine and daunorubicin achieved superior results in these difficult to treat patients.

[email protected]

On Twitter @maryjodales

CHICAGO – The investigational drug CPX-351 (Vyxeos) may become the new standard of care for older patients with secondary acute myeloid leukemia (AML), based on data presented at the annual meeting of the American Society of Clinical Oncology.

CPX-351 significantly improved overall survival, event-free survival, and treatment response without an increase in 60-day mortality or in the frequency and severity of adverse events as compared to the standard 7+3 regimen of cytarabine and daunorubicin.

In a video interview, primary investigator Dr. Jeffrey Lancet of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla., discusses the data to be presented to the Food and Drug Administration for approval of the drug, and why the liposomal formulation of cytarabine and daunorubicin achieved superior results in these difficult to treat patients.

[email protected]

On Twitter @maryjodales

CHICAGO – The investigational drug CPX-351 (Vyxeos) may become the new standard of care for older patients with secondary acute myeloid leukemia (AML), based on data presented at the annual meeting of the American Society of Clinical Oncology.

CPX-351 significantly improved overall survival, event-free survival, and treatment response without an increase in 60-day mortality or in the frequency and severity of adverse events as compared to the standard 7+3 regimen of cytarabine and daunorubicin.

In a video interview, primary investigator Dr. Jeffrey Lancet of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla., discusses the data to be presented to the Food and Drug Administration for approval of the drug, and why the liposomal formulation of cytarabine and daunorubicin achieved superior results in these difficult to treat patients.

[email protected]

On Twitter @maryjodales

To improve patient care and outcomes, leading dermatologists offered their recommendations on body scrubs. Consideration must be given to:

• Almond Shower Scrub

• Gently Exfoliating Body Scrub

• Peppermint Body Scrub

• Shea Butter Ultra Rich Body Scrub

• Ultimate Man Body Scrub Soap

Cutis invites readers to send us their recommendations. Body scrubs, OTC acne treatments, and cleansing devices will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on body scrubs. Consideration must be given to:

• Almond Shower Scrub

• Gently Exfoliating Body Scrub

• Peppermint Body Scrub

• Shea Butter Ultra Rich Body Scrub

• Ultimate Man Body Scrub Soap

Cutis invites readers to send us their recommendations. Body scrubs, OTC acne treatments, and cleansing devices will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on body scrubs. Consideration must be given to:

• Almond Shower Scrub

• Gently Exfoliating Body Scrub

• Peppermint Body Scrub

• Shea Butter Ultra Rich Body Scrub

• Ultimate Man Body Scrub Soap

Cutis invites readers to send us their recommendations. Body scrubs, OTC acne treatments, and cleansing devices will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

Two tools – the Vascular Annual Meeting Mobile App and the Meeting Itinerary Planner – will make VAM 2016 a user-friendly experience.

The App

The SVS Vascular Annual Meeting Mobile App puts the entire meeting at attendees’ fingertips. It includes:

• All meeting content, including abstracts, speakers, sessions and more

• A searchable format, letting people locate sessions, abstracts, room locations and more

• Interactivity: People may network with colleagues, share photos and rate programs, take notes and use the activity feed available for each session.

 New this year is a link that lets participants access the CME and MOC sites, to take credit exams after a session ends. It also includes links to claim credits.

Download the app here.

The Itinerary Planner

The Itinerary Planner is a web-based tool that includes all VAM details, such as full and daily schedules; links to authors, abstracts and speaker bios; special events; programming for fellows/residents/students; registration information, Vascular Live details and all other VAM info.

The detailed Users will be able to build personal schedules with their own “must-attend” events and sessions by bookmarking items of interest, plus:

• View session, faculty and exhibitor information in real time.

• Search for presentations by day, type, individual or keyword.

• Add in personal meetings or events.

• Export and email their calendar to share with others.

• Access the site via mobile and traditional platforms.

Please note that schedules and agendas created on the Itinerary Planner do NOT sync with the schedule in the Mobile App.

Access the planner here.

Two tools – the Vascular Annual Meeting Mobile App and the Meeting Itinerary Planner – will make VAM 2016 a user-friendly experience.

The App

The SVS Vascular Annual Meeting Mobile App puts the entire meeting at attendees’ fingertips. It includes:

• All meeting content, including abstracts, speakers, sessions and more

• A searchable format, letting people locate sessions, abstracts, room locations and more

• Interactivity: People may network with colleagues, share photos and rate programs, take notes and use the activity feed available for each session.

 New this year is a link that lets participants access the CME and MOC sites, to take credit exams after a session ends. It also includes links to claim credits.

Download the app here.

The Itinerary Planner

The Itinerary Planner is a web-based tool that includes all VAM details, such as full and daily schedules; links to authors, abstracts and speaker bios; special events; programming for fellows/residents/students; registration information, Vascular Live details and all other VAM info.

The detailed Users will be able to build personal schedules with their own “must-attend” events and sessions by bookmarking items of interest, plus:

• View session, faculty and exhibitor information in real time.

• Search for presentations by day, type, individual or keyword.

• Add in personal meetings or events.

• Export and email their calendar to share with others.

• Access the site via mobile and traditional platforms.

Please note that schedules and agendas created on the Itinerary Planner do NOT sync with the schedule in the Mobile App.

Access the planner here.

Two tools – the Vascular Annual Meeting Mobile App and the Meeting Itinerary Planner – will make VAM 2016 a user-friendly experience.

The App

The SVS Vascular Annual Meeting Mobile App puts the entire meeting at attendees’ fingertips. It includes:

• All meeting content, including abstracts, speakers, sessions and more

• A searchable format, letting people locate sessions, abstracts, room locations and more

• Interactivity: People may network with colleagues, share photos and rate programs, take notes and use the activity feed available for each session.

 New this year is a link that lets participants access the CME and MOC sites, to take credit exams after a session ends. It also includes links to claim credits.

Download the app here.

The Itinerary Planner

The Itinerary Planner is a web-based tool that includes all VAM details, such as full and daily schedules; links to authors, abstracts and speaker bios; special events; programming for fellows/residents/students; registration information, Vascular Live details and all other VAM info.

The detailed Users will be able to build personal schedules with their own “must-attend” events and sessions by bookmarking items of interest, plus:

• View session, faculty and exhibitor information in real time.

• Search for presentations by day, type, individual or keyword.

• Add in personal meetings or events.

• Export and email their calendar to share with others.

• Access the site via mobile and traditional platforms.

Please note that schedules and agendas created on the Itinerary Planner do NOT sync with the schedule in the Mobile App.

Access the planner here.

Exhibits, speakers, plenaries, hands-on sessions. Networking, dinner with friends, alumni receptions, the Capitol Steps comedy act. All this and much more is on tap during the 2016 Vascular Annual Meeting slated for June 8-11, just outside Washington, D.C. Plenaries and exhibits begin June 9. Registration is open throughout the conference.

Vascular surgeons, specialists, medical professionals in related fields, device manufacturers and others will meet at the Gaylord National Resort & Convention Center in National Harbor, Maryland, just minutes away from Washington, D.C.

Thanks to popular demand, each year the annual meeting -- often called VAM -- expands a little more on Wednesday and Saturday to accommodate more events and opportunities. This year Wednesday and Saturday are filled with events and sessions that attendees won’t want to miss. Workshops ($100 fee), international events and a full day of Vascular Quality Initiative sessions will be on Wednesday. Thursday and Friday feature more plenaries, talks by vascular luminaries, receptions, breakfast and evening events. On Saturday the annual SVS business meeting, the exhibit hall and credit-worthy plenaries will be good reasons to stay through the end.

A highlight this year will be a Friday June 10 evening performance by the Capitol Steps, a comedy troupe based in D.C. known for their cutting edge, political humor. It will be open to all attendees, exhibitors and their guests.

2016 VAM offers a variety of postgraduate courses on Wednesday designed for surgeons, physicians in related specialties, trainees, interventional radiologists, physician assistants and vascular nurses, researchers, allied health professionals and medical students. Postgraduate courses are complimentary for SVS members but separate registration is required.

This year’s events offer a maximum of 30.25 AMA PRA Category 1 Credits™ with 13.25 AMA PRA Category 1 Credits™ counted toward MOC part 2. Each of the seven plenary sessions has individual self-assessments. This year, claiming your credits is easier than ever. A self-assessment exam is available on the meeting app and can be completed immediately following each session.

Registration is open through the end of the event, and may be completed online at www.vsweb.org/RegisterVAM16. There are 10 different registration fees that vary by category. For example, active members pay $650; medical students, $300; non-members $845. In addition, there are still some seats left in the hands-on workshops offered on Wednesday, June 8. Topics include Carotid Stenting, IVC Filters: Techniques in Deployment and Recovery and much more. See all topics.

The conference location, Gaylord National Resort & Convention Center, offers sweeping views of the Potomac River, Washington, D.C. and Old Town Alexandria. As the cornerstone of the new National Harbor project in Prince George’s County, Maryland, the resort includes an 18-story glass atrium overlooking the Potomac, three restaurants, including fine dining and casual, a rooftop lounge, express coffee outlet, unique shops, an indoor pool and a 20,000 square-foot spa and fitness center. The 300-acre site also features tree-lined promenades with shops and restaurants, two marinas, a Ferris wheel and much more. For a complete directory as well as an interactive map, please visit the Gaylord National Resort & Conference Center website.

The weather in Washington D.C. in early June averages a high of 83 and low of 65, Fahrenheit. Attire is business casual during the day and resort casual for hospitality events.

Click here for more 2016 VAM Information.

Exhibits, speakers, plenaries, hands-on sessions. Networking, dinner with friends, alumni receptions, the Capitol Steps comedy act. All this and much more is on tap during the 2016 Vascular Annual Meeting slated for June 8-11, just outside Washington, D.C. Plenaries and exhibits begin June 9. Registration is open throughout the conference.

Vascular surgeons, specialists, medical professionals in related fields, device manufacturers and others will meet at the Gaylord National Resort & Convention Center in National Harbor, Maryland, just minutes away from Washington, D.C.

Thanks to popular demand, each year the annual meeting -- often called VAM -- expands a little more on Wednesday and Saturday to accommodate more events and opportunities. This year Wednesday and Saturday are filled with events and sessions that attendees won’t want to miss. Workshops ($100 fee), international events and a full day of Vascular Quality Initiative sessions will be on Wednesday. Thursday and Friday feature more plenaries, talks by vascular luminaries, receptions, breakfast and evening events. On Saturday the annual SVS business meeting, the exhibit hall and credit-worthy plenaries will be good reasons to stay through the end.

A highlight this year will be a Friday June 10 evening performance by the Capitol Steps, a comedy troupe based in D.C. known for their cutting edge, political humor. It will be open to all attendees, exhibitors and their guests.

2016 VAM offers a variety of postgraduate courses on Wednesday designed for surgeons, physicians in related specialties, trainees, interventional radiologists, physician assistants and vascular nurses, researchers, allied health professionals and medical students. Postgraduate courses are complimentary for SVS members but separate registration is required.

This year’s events offer a maximum of 30.25 AMA PRA Category 1 Credits™ with 13.25 AMA PRA Category 1 Credits™ counted toward MOC part 2. Each of the seven plenary sessions has individual self-assessments. This year, claiming your credits is easier than ever. A self-assessment exam is available on the meeting app and can be completed immediately following each session.

Registration is open through the end of the event, and may be completed online at www.vsweb.org/RegisterVAM16. There are 10 different registration fees that vary by category. For example, active members pay $650; medical students, $300; non-members $845. In addition, there are still some seats left in the hands-on workshops offered on Wednesday, June 8. Topics include Carotid Stenting, IVC Filters: Techniques in Deployment and Recovery and much more. See all topics.

The conference location, Gaylord National Resort & Convention Center, offers sweeping views of the Potomac River, Washington, D.C. and Old Town Alexandria. As the cornerstone of the new National Harbor project in Prince George’s County, Maryland, the resort includes an 18-story glass atrium overlooking the Potomac, three restaurants, including fine dining and casual, a rooftop lounge, express coffee outlet, unique shops, an indoor pool and a 20,000 square-foot spa and fitness center. The 300-acre site also features tree-lined promenades with shops and restaurants, two marinas, a Ferris wheel and much more. For a complete directory as well as an interactive map, please visit the Gaylord National Resort & Conference Center website.

The weather in Washington D.C. in early June averages a high of 83 and low of 65, Fahrenheit. Attire is business casual during the day and resort casual for hospitality events.

Click here for more 2016 VAM Information.

Exhibits, speakers, plenaries, hands-on sessions. Networking, dinner with friends, alumni receptions, the Capitol Steps comedy act. All this and much more is on tap during the 2016 Vascular Annual Meeting slated for June 8-11, just outside Washington, D.C. Plenaries and exhibits begin June 9. Registration is open throughout the conference.

Vascular surgeons, specialists, medical professionals in related fields, device manufacturers and others will meet at the Gaylord National Resort & Convention Center in National Harbor, Maryland, just minutes away from Washington, D.C.

Thanks to popular demand, each year the annual meeting -- often called VAM -- expands a little more on Wednesday and Saturday to accommodate more events and opportunities. This year Wednesday and Saturday are filled with events and sessions that attendees won’t want to miss. Workshops ($100 fee), international events and a full day of Vascular Quality Initiative sessions will be on Wednesday. Thursday and Friday feature more plenaries, talks by vascular luminaries, receptions, breakfast and evening events. On Saturday the annual SVS business meeting, the exhibit hall and credit-worthy plenaries will be good reasons to stay through the end.

A highlight this year will be a Friday June 10 evening performance by the Capitol Steps, a comedy troupe based in D.C. known for their cutting edge, political humor. It will be open to all attendees, exhibitors and their guests.

2016 VAM offers a variety of postgraduate courses on Wednesday designed for surgeons, physicians in related specialties, trainees, interventional radiologists, physician assistants and vascular nurses, researchers, allied health professionals and medical students. Postgraduate courses are complimentary for SVS members but separate registration is required.

This year’s events offer a maximum of 30.25 AMA PRA Category 1 Credits™ with 13.25 AMA PRA Category 1 Credits™ counted toward MOC part 2. Each of the seven plenary sessions has individual self-assessments. This year, claiming your credits is easier than ever. A self-assessment exam is available on the meeting app and can be completed immediately following each session.

Registration is open through the end of the event, and may be completed online at www.vsweb.org/RegisterVAM16. There are 10 different registration fees that vary by category. For example, active members pay $650; medical students, $300; non-members $845. In addition, there are still some seats left in the hands-on workshops offered on Wednesday, June 8. Topics include Carotid Stenting, IVC Filters: Techniques in Deployment and Recovery and much more. See all topics.

The conference location, Gaylord National Resort & Convention Center, offers sweeping views of the Potomac River, Washington, D.C. and Old Town Alexandria. As the cornerstone of the new National Harbor project in Prince George’s County, Maryland, the resort includes an 18-story glass atrium overlooking the Potomac, three restaurants, including fine dining and casual, a rooftop lounge, express coffee outlet, unique shops, an indoor pool and a 20,000 square-foot spa and fitness center. The 300-acre site also features tree-lined promenades with shops and restaurants, two marinas, a Ferris wheel and much more. For a complete directory as well as an interactive map, please visit the Gaylord National Resort & Conference Center website.

The weather in Washington D.C. in early June averages a high of 83 and low of 65, Fahrenheit. Attire is business casual during the day and resort casual for hospitality events.

Click here for more 2016 VAM Information.

LOS ANGELES – The inpatient use of infliximab for severe ulcerative colitis does not avoid the need for colectomy in patients who fail steroid therapy, results from a single-center study demonstrated.

In an interview at the annual meeting of the American Society of Colon and Rectal Surgeons, lead study author Dr. Rachel E. Andrew, a third-year resident in the department of surgery at Penn State Hershey Medical Center in Hershey, Pa., said that despite recent interest in providing inpatient infliximab as an alternative to surgery for those with steroid-refractory disease, 82% of those who received salvage infliximab went on to undergo a total abdominal colectomy during the same admission.

“Our findings suggest that inpatient infliximab was not effective at improving the severity of colitis in these patients,” she said. “Further, infliximab was unreliable in avoiding the need for a total colectomy in this population of ulcerative colitis patients. One difference between our study and those previously published on this subject is that our study focuses on patients with a severity of colitis that resulted in their admission to a surgery service. In terms of evaluating the benefit of infliximab and providing a reliable avoidance of colectomy, we feel that this population of ulcerative colitis patients would be most appropriate to evaluate this issue. This possible difference in patient population may explain the difference in our study findings and those previously published.”

The researchers compared colectomy rates in 173 patients with severe ulcerative colitis who were admitted to the colorectal surgery service at Penn State Hershey Medical Center. Their mean age was 41 years, with 155 (90%) treated with high-dose steroids alone, and with 18 (10%) having received inpatient infliximab as salvage therapy due to a lack of response to steroids alone. Of the patients who received high-dose steroids alone, 81 (52%) required total colectomy, compared with 14 (82%) who received infliximab salvage therapy (P = .046).

The researchers observed no statistically significant differences between the two groups regarding rates of hospital readmission, superficial, deep and organ space surgical-site infections, unplanned return to the operating room, and all complication rates (P greater than .05). Among patients who required total colectomy, hospital costs were 27% higher among those who received infliximab compared with those who received high-dose steroids alone (a mean of $19,880 vs. $14,492, respectively), but because of the small sample size of the infliximab cohort this difference did not reach statistical significance.

“In our institution, salvage infliximab has not been shown to be effective,” Dr. Andrew said. “One key difference between our findings and other studies is that our study population had a high colectomy rate; 82% is much higher than the approximately 30% colectomy rate described in many reports from colleagues in gastroenterology. While there are several potential explanations for our higher rate of colectomy, including the potential concerns that surgeons might be inclined to opt for surgery more readily than non-surgical providers, it is likely that the patients in our study had more severe forms of colitis. It might be the case that there are certain severities of colitis that are beyond the ability of infliximab to salvage, which would be an important issue in selecting which patients to provide inpatient infliximab, so as to not unnecessarily delay surgery, increase hospital costs and to avoid escalating the degree of immunosuppression without a reasonable likelihood of clinical improvement.”

Dr. Andrew reported having no financial disclosures.

[email protected]

LOS ANGELES – The inpatient use of infliximab for severe ulcerative colitis does not avoid the need for colectomy in patients who fail steroid therapy, results from a single-center study demonstrated.

In an interview at the annual meeting of the American Society of Colon and Rectal Surgeons, lead study author Dr. Rachel E. Andrew, a third-year resident in the department of surgery at Penn State Hershey Medical Center in Hershey, Pa., said that despite recent interest in providing inpatient infliximab as an alternative to surgery for those with steroid-refractory disease, 82% of those who received salvage infliximab went on to undergo a total abdominal colectomy during the same admission.

“Our findings suggest that inpatient infliximab was not effective at improving the severity of colitis in these patients,” she said. “Further, infliximab was unreliable in avoiding the need for a total colectomy in this population of ulcerative colitis patients. One difference between our study and those previously published on this subject is that our study focuses on patients with a severity of colitis that resulted in their admission to a surgery service. In terms of evaluating the benefit of infliximab and providing a reliable avoidance of colectomy, we feel that this population of ulcerative colitis patients would be most appropriate to evaluate this issue. This possible difference in patient population may explain the difference in our study findings and those previously published.”

The researchers compared colectomy rates in 173 patients with severe ulcerative colitis who were admitted to the colorectal surgery service at Penn State Hershey Medical Center. Their mean age was 41 years, with 155 (90%) treated with high-dose steroids alone, and with 18 (10%) having received inpatient infliximab as salvage therapy due to a lack of response to steroids alone. Of the patients who received high-dose steroids alone, 81 (52%) required total colectomy, compared with 14 (82%) who received infliximab salvage therapy (P = .046).

The researchers observed no statistically significant differences between the two groups regarding rates of hospital readmission, superficial, deep and organ space surgical-site infections, unplanned return to the operating room, and all complication rates (P greater than .05). Among patients who required total colectomy, hospital costs were 27% higher among those who received infliximab compared with those who received high-dose steroids alone (a mean of $19,880 vs. $14,492, respectively), but because of the small sample size of the infliximab cohort this difference did not reach statistical significance.

“In our institution, salvage infliximab has not been shown to be effective,” Dr. Andrew said. “One key difference between our findings and other studies is that our study population had a high colectomy rate; 82% is much higher than the approximately 30% colectomy rate described in many reports from colleagues in gastroenterology. While there are several potential explanations for our higher rate of colectomy, including the potential concerns that surgeons might be inclined to opt for surgery more readily than non-surgical providers, it is likely that the patients in our study had more severe forms of colitis. It might be the case that there are certain severities of colitis that are beyond the ability of infliximab to salvage, which would be an important issue in selecting which patients to provide inpatient infliximab, so as to not unnecessarily delay surgery, increase hospital costs and to avoid escalating the degree of immunosuppression without a reasonable likelihood of clinical improvement.”

Dr. Andrew reported having no financial disclosures.

[email protected]

LOS ANGELES – The inpatient use of infliximab for severe ulcerative colitis does not avoid the need for colectomy in patients who fail steroid therapy, results from a single-center study demonstrated.

In an interview at the annual meeting of the American Society of Colon and Rectal Surgeons, lead study author Dr. Rachel E. Andrew, a third-year resident in the department of surgery at Penn State Hershey Medical Center in Hershey, Pa., said that despite recent interest in providing inpatient infliximab as an alternative to surgery for those with steroid-refractory disease, 82% of those who received salvage infliximab went on to undergo a total abdominal colectomy during the same admission.

“Our findings suggest that inpatient infliximab was not effective at improving the severity of colitis in these patients,” she said. “Further, infliximab was unreliable in avoiding the need for a total colectomy in this population of ulcerative colitis patients. One difference between our study and those previously published on this subject is that our study focuses on patients with a severity of colitis that resulted in their admission to a surgery service. In terms of evaluating the benefit of infliximab and providing a reliable avoidance of colectomy, we feel that this population of ulcerative colitis patients would be most appropriate to evaluate this issue. This possible difference in patient population may explain the difference in our study findings and those previously published.”

The researchers compared colectomy rates in 173 patients with severe ulcerative colitis who were admitted to the colorectal surgery service at Penn State Hershey Medical Center. Their mean age was 41 years, with 155 (90%) treated with high-dose steroids alone, and with 18 (10%) having received inpatient infliximab as salvage therapy due to a lack of response to steroids alone. Of the patients who received high-dose steroids alone, 81 (52%) required total colectomy, compared with 14 (82%) who received infliximab salvage therapy (P = .046).

The researchers observed no statistically significant differences between the two groups regarding rates of hospital readmission, superficial, deep and organ space surgical-site infections, unplanned return to the operating room, and all complication rates (P greater than .05). Among patients who required total colectomy, hospital costs were 27% higher among those who received infliximab compared with those who received high-dose steroids alone (a mean of $19,880 vs. $14,492, respectively), but because of the small sample size of the infliximab cohort this difference did not reach statistical significance.

“In our institution, salvage infliximab has not been shown to be effective,” Dr. Andrew said. “One key difference between our findings and other studies is that our study population had a high colectomy rate; 82% is much higher than the approximately 30% colectomy rate described in many reports from colleagues in gastroenterology. While there are several potential explanations for our higher rate of colectomy, including the potential concerns that surgeons might be inclined to opt for surgery more readily than non-surgical providers, it is likely that the patients in our study had more severe forms of colitis. It might be the case that there are certain severities of colitis that are beyond the ability of infliximab to salvage, which would be an important issue in selecting which patients to provide inpatient infliximab, so as to not unnecessarily delay surgery, increase hospital costs and to avoid escalating the degree of immunosuppression without a reasonable likelihood of clinical improvement.”

Dr. Andrew reported having no financial disclosures.

[email protected]

Clinical question: What is the association between detectable cardiac troponin (cTn) levels and outcomes in persons hospitalized with acute decompensated heart failure (ADHF)?

Background: There are millions of ADHF hospitalizations per year, and all-cause mortality and readmission rates are high. Efforts to better risk-stratify such patients have included measuring cTn levels and determining risk of increased length of stay, hospital readmission, and mortality.

Study design: Systematic review and meta-analysis.

Setting: Twenty-six observational cohort studies.

Synopsis: Compared with an undetectable cTn, detectable or elevated cTn levels were associated with greater length of stay (odds ratio [OR], 1.05; 95% CI, 1.01¬–1.10) and greater in-hospital death (OR, 2.57; 95% CI, 2.27–2.91). ADHF patients with detectable or elevated cTn were also at increased risk for mortality and composite of mortality and readmission over the short, intermediate, and long term. Reviewers eventually considered the overall association of a detectable or elevated troponin with mortality and readmission as moderate (relative association measure >2.0).

Meanwhile, few studies in this analysis showed a continuous and graded relationship between cTn levels and clinical outcomes.

Limitations of the review include arbitrarily stratifying groups by the level of cTn from assays whose lower limit of detection vary. The authors also admit the various associations are likely affected by several confounders for which they could not adjust because individual participant data were unavailable.

Finally, while acknowledging patients with chronic stable heart failure often have baseline elevated cTn levels, accounting for this in the analysis was limited.

Bottom line: A detectable or elevated level of cTn during ADHF hospitalization leads to worse outcomes both during and after discharge.

Citation: Yousufuddin M, Abdalrhim AD, Wang Z, Murad MH. Cardiac troponin in patients hospitalized with acute decompensated heart failure: a systematic review and meta-analysis [published online ahead of print February 18, 2016]. J Hosp Med. doi:10.1002/jhm.2558.

Clinical question: What is the association between detectable cardiac troponin (cTn) levels and outcomes in persons hospitalized with acute decompensated heart failure (ADHF)?

Background: There are millions of ADHF hospitalizations per year, and all-cause mortality and readmission rates are high. Efforts to better risk-stratify such patients have included measuring cTn levels and determining risk of increased length of stay, hospital readmission, and mortality.

Study design: Systematic review and meta-analysis.

Setting: Twenty-six observational cohort studies.

Synopsis: Compared with an undetectable cTn, detectable or elevated cTn levels were associated with greater length of stay (odds ratio [OR], 1.05; 95% CI, 1.01¬–1.10) and greater in-hospital death (OR, 2.57; 95% CI, 2.27–2.91). ADHF patients with detectable or elevated cTn were also at increased risk for mortality and composite of mortality and readmission over the short, intermediate, and long term. Reviewers eventually considered the overall association of a detectable or elevated troponin with mortality and readmission as moderate (relative association measure >2.0).

Meanwhile, few studies in this analysis showed a continuous and graded relationship between cTn levels and clinical outcomes.

Limitations of the review include arbitrarily stratifying groups by the level of cTn from assays whose lower limit of detection vary. The authors also admit the various associations are likely affected by several confounders for which they could not adjust because individual participant data were unavailable.

Finally, while acknowledging patients with chronic stable heart failure often have baseline elevated cTn levels, accounting for this in the analysis was limited.

Bottom line: A detectable or elevated level of cTn during ADHF hospitalization leads to worse outcomes both during and after discharge.

Citation: Yousufuddin M, Abdalrhim AD, Wang Z, Murad MH. Cardiac troponin in patients hospitalized with acute decompensated heart failure: a systematic review and meta-analysis [published online ahead of print February 18, 2016]. J Hosp Med. doi:10.1002/jhm.2558.

Clinical question: What is the association between detectable cardiac troponin (cTn) levels and outcomes in persons hospitalized with acute decompensated heart failure (ADHF)?

Background: There are millions of ADHF hospitalizations per year, and all-cause mortality and readmission rates are high. Efforts to better risk-stratify such patients have included measuring cTn levels and determining risk of increased length of stay, hospital readmission, and mortality.

Study design: Systematic review and meta-analysis.

Setting: Twenty-six observational cohort studies.

Synopsis: Compared with an undetectable cTn, detectable or elevated cTn levels were associated with greater length of stay (odds ratio [OR], 1.05; 95% CI, 1.01¬–1.10) and greater in-hospital death (OR, 2.57; 95% CI, 2.27–2.91). ADHF patients with detectable or elevated cTn were also at increased risk for mortality and composite of mortality and readmission over the short, intermediate, and long term. Reviewers eventually considered the overall association of a detectable or elevated troponin with mortality and readmission as moderate (relative association measure >2.0).

Meanwhile, few studies in this analysis showed a continuous and graded relationship between cTn levels and clinical outcomes.

Limitations of the review include arbitrarily stratifying groups by the level of cTn from assays whose lower limit of detection vary. The authors also admit the various associations are likely affected by several confounders for which they could not adjust because individual participant data were unavailable.

Finally, while acknowledging patients with chronic stable heart failure often have baseline elevated cTn levels, accounting for this in the analysis was limited.

Bottom line: A detectable or elevated level of cTn during ADHF hospitalization leads to worse outcomes both during and after discharge.

Citation: Yousufuddin M, Abdalrhim AD, Wang Z, Murad MH. Cardiac troponin in patients hospitalized with acute decompensated heart failure: a systematic review and meta-analysis [published online ahead of print February 18, 2016]. J Hosp Med. doi:10.1002/jhm.2558.

Clinical question: Which cardiovascular imaging modalities can augment triage of ED patients with chest pain?

Background: Because absolute event rates for patients with chest pain and normal initial ECG findings are not low enough to drive discharge triage decisions, and findings that patients with acute myocardial infarction (AMI) are inadvertently discharged because of less-sensitive troponin assays, there is great interest in what imaging modalities can facilitate safer triages.

Study design: Clinical guideline.

Setting: Meta-analysis of studies in multiple clinical settings.

Synopsis: This guideline adopted two pathways: an early assessment pathway, which considers imaging without the need for serial biomarker analysis, and an observational pathway, which involves serial biomarker testing.

For the early assessment pathway, when ECG and/or biomarker analysis is unequivocally positive for ischemia, all rest-imaging modalities are rarely appropriate. When the initial troponin level is equivocal, both rest single-photon emission computed tomography (SPECT) and coronary CT angiography (CCTA) are appropriate, though rest echocardiography and rest cardiovascular magnetic resonance (CMR) may be alternatives. Resting imaging may also be appropriate when chest pain resolves prior to evaluation and/or initial ECG plus troponin is non-ischemic/normal.

In the observational pathway, for patients with ECG changes and/or serial troponins unequivocally positive for AMI, only cardiac catheterization is recommended. When serial ECGs/troponins are borderline, stress-test modalities and CCTA are appropriate. When serial ECGs/ troponins are negative, outpatient testing may be appropriate.

Bottom line: Experts recommend cardiac catheterization as the imaging modality of choice for patients with an unequivocal AMI diagnosis. When ECG and/or biomarkers are equivocal or negative, outpatient evaluation may be appropriate.

Citation: Rybicki FJ, Udelson JE, Peacock WF, et al. Appropriate utilization of cardiovascular imaging in emergency department patients with chest pain: a joint document of the American College of Radiology Appropriateness Criteria Committee and the American College of Cardiology Appropriate Use Criteria Task Force. J Am Coll Radiol. 2016;(2):e1-e29. doi:10.1016/j.jacr.2015.07.007.

Short Take

Family Reflections on End-of-Life Cancer Care

In this multicenter, prospective, observational study, family members of patients with advanced-stage cancer who received aggressive care at end of life were less likely to report the overall quality of end-of-life care as “excellent” or “very good.”

Citation: Wright AA, Keating NL, Ayanian JZ, et al. Family perspectives on aggressive cancer care near the end of life. JAMA. 2016;315(3):284-292.

Clinical question: Which cardiovascular imaging modalities can augment triage of ED patients with chest pain?

Background: Because absolute event rates for patients with chest pain and normal initial ECG findings are not low enough to drive discharge triage decisions, and findings that patients with acute myocardial infarction (AMI) are inadvertently discharged because of less-sensitive troponin assays, there is great interest in what imaging modalities can facilitate safer triages.

Study design: Clinical guideline.

Setting: Meta-analysis of studies in multiple clinical settings.

Synopsis: This guideline adopted two pathways: an early assessment pathway, which considers imaging without the need for serial biomarker analysis, and an observational pathway, which involves serial biomarker testing.

For the early assessment pathway, when ECG and/or biomarker analysis is unequivocally positive for ischemia, all rest-imaging modalities are rarely appropriate. When the initial troponin level is equivocal, both rest single-photon emission computed tomography (SPECT) and coronary CT angiography (CCTA) are appropriate, though rest echocardiography and rest cardiovascular magnetic resonance (CMR) may be alternatives. Resting imaging may also be appropriate when chest pain resolves prior to evaluation and/or initial ECG plus troponin is non-ischemic/normal.

In the observational pathway, for patients with ECG changes and/or serial troponins unequivocally positive for AMI, only cardiac catheterization is recommended. When serial ECGs/troponins are borderline, stress-test modalities and CCTA are appropriate. When serial ECGs/ troponins are negative, outpatient testing may be appropriate.

Bottom line: Experts recommend cardiac catheterization as the imaging modality of choice for patients with an unequivocal AMI diagnosis. When ECG and/or biomarkers are equivocal or negative, outpatient evaluation may be appropriate.

Citation: Rybicki FJ, Udelson JE, Peacock WF, et al. Appropriate utilization of cardiovascular imaging in emergency department patients with chest pain: a joint document of the American College of Radiology Appropriateness Criteria Committee and the American College of Cardiology Appropriate Use Criteria Task Force. J Am Coll Radiol. 2016;(2):e1-e29. doi:10.1016/j.jacr.2015.07.007.

Short Take

Family Reflections on End-of-Life Cancer Care

In this multicenter, prospective, observational study, family members of patients with advanced-stage cancer who received aggressive care at end of life were less likely to report the overall quality of end-of-life care as “excellent” or “very good.”

Citation: Wright AA, Keating NL, Ayanian JZ, et al. Family perspectives on aggressive cancer care near the end of life. JAMA. 2016;315(3):284-292.

Clinical question: Which cardiovascular imaging modalities can augment triage of ED patients with chest pain?

Background: Because absolute event rates for patients with chest pain and normal initial ECG findings are not low enough to drive discharge triage decisions, and findings that patients with acute myocardial infarction (AMI) are inadvertently discharged because of less-sensitive troponin assays, there is great interest in what imaging modalities can facilitate safer triages.

Study design: Clinical guideline.

Setting: Meta-analysis of studies in multiple clinical settings.

Synopsis: This guideline adopted two pathways: an early assessment pathway, which considers imaging without the need for serial biomarker analysis, and an observational pathway, which involves serial biomarker testing.

For the early assessment pathway, when ECG and/or biomarker analysis is unequivocally positive for ischemia, all rest-imaging modalities are rarely appropriate. When the initial troponin level is equivocal, both rest single-photon emission computed tomography (SPECT) and coronary CT angiography (CCTA) are appropriate, though rest echocardiography and rest cardiovascular magnetic resonance (CMR) may be alternatives. Resting imaging may also be appropriate when chest pain resolves prior to evaluation and/or initial ECG plus troponin is non-ischemic/normal.

In the observational pathway, for patients with ECG changes and/or serial troponins unequivocally positive for AMI, only cardiac catheterization is recommended. When serial ECGs/troponins are borderline, stress-test modalities and CCTA are appropriate. When serial ECGs/ troponins are negative, outpatient testing may be appropriate.

Bottom line: Experts recommend cardiac catheterization as the imaging modality of choice for patients with an unequivocal AMI diagnosis. When ECG and/or biomarkers are equivocal or negative, outpatient evaluation may be appropriate.

Citation: Rybicki FJ, Udelson JE, Peacock WF, et al. Appropriate utilization of cardiovascular imaging in emergency department patients with chest pain: a joint document of the American College of Radiology Appropriateness Criteria Committee and the American College of Cardiology Appropriate Use Criteria Task Force. J Am Coll Radiol. 2016;(2):e1-e29. doi:10.1016/j.jacr.2015.07.007.

Short Take

Family Reflections on End-of-Life Cancer Care

In this multicenter, prospective, observational study, family members of patients with advanced-stage cancer who received aggressive care at end of life were less likely to report the overall quality of end-of-life care as “excellent” or “very good.”

Citation: Wright AA, Keating NL, Ayanian JZ, et al. Family perspectives on aggressive cancer care near the end of life. JAMA. 2016;315(3):284-292.

Ibrutinib (Imbruvica)
Photo from Janssen Biotech

The European Commission (EC) has broadened the indication for ibrutinib (Imbruvica) to include newly diagnosed patients with chronic lymphocytic leukemia (CLL).

The drug had already been approved in the European Union to treat adults with CLL who have received at least one prior therapy and adults with previously untreated CLL who have 17p deletion or TP53 mutation and are unsuitable for chemo-immunotherapy. 

Ibrutinib is now approved for all patients with CLL.

The EC is following the recommendation of the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP), which had previously sent its endorsement to the EC.

This approval also follows the decision by the US Food and Drug Administration in March to approve the expanded use of ibrutinib capsules for treatment-naïve patients with CLL.

Ibrutinib is also approved to treat adults with relapsed or refractory mantle cell lymphoma, adults with Waldenström’s macroglobulinemia who have received at least one prior therapy, and previously untreated adults with Waldenström’s macroglobulinemia who are unsuitable for chemo-immunotherapy.

RESONATE-2 trial

The expanded ibrutinib indication is based on data from the phase 3, randomized, open-label RESONATE-2 trial, published in NEJM in 2015.

Results from the RESONATE-2 study showed that ibrutinib significantly prolonged overall survival (OS) (HR=0.16, 95 percent CI 0.05 to 0.56; P=0.001).

Ninety-eight percent of patients were still alive after 2 years, compared to 85% percent for patients randomized to the chlorambucil arm. 

Median progression-free survival (PFS) was not reached for patients receiving ibrutinib versus 18.9 months for those in the chlorambucil arm. This represented a statistically significant 84% reduction in the risk of death or progression in the ibrutinib arm (HR=0.16, 95 percent CI 0.09 to 0.28; P<0.001). 

“Ibrutinib has shown remarkable improvements in overall survival, progression-free survival, and response rates compared with chlorambucil,” said Paolo Ghia, MD, PhD, one of the RESONATE-2 investigators.

The overall safety of ibrutinib in the treatment-naïve CLL patient population was consistent with previously reported studies. 

The most common adverse events for ibrutinib of any grade occurring in 20% or more of the patients were diarrhea (42%), fatigue (30%), cough (22%), and nausea (22%).

“The RESONATE-2 data indicate that ibrutinib can provide a much-needed first line treatment alternative for many patients,” Dr Ghia affirmed.

Ibrutinib is co-developed by Cilag GmbH International, a member of the Janssen Pharmaceutical Companies, and Pharmacyclics LLC, an AbbVie company. Janssen affiliates market ibrutinib in all approved countries except the US. In the US, Janssen Biotech, Inc. and Pharmacyclics co-market it.

Ibrutinib (Imbruvica)
Photo from Janssen Biotech

The European Commission (EC) has broadened the indication for ibrutinib (Imbruvica) to include newly diagnosed patients with chronic lymphocytic leukemia (CLL).

The drug had already been approved in the European Union to treat adults with CLL who have received at least one prior therapy and adults with previously untreated CLL who have 17p deletion or TP53 mutation and are unsuitable for chemo-immunotherapy. 

Ibrutinib is now approved for all patients with CLL.

The EC is following the recommendation of the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP), which had previously sent its endorsement to the EC.

This approval also follows the decision by the US Food and Drug Administration in March to approve the expanded use of ibrutinib capsules for treatment-naïve patients with CLL.

Ibrutinib is also approved to treat adults with relapsed or refractory mantle cell lymphoma, adults with Waldenström’s macroglobulinemia who have received at least one prior therapy, and previously untreated adults with Waldenström’s macroglobulinemia who are unsuitable for chemo-immunotherapy.

RESONATE-2 trial

The expanded ibrutinib indication is based on data from the phase 3, randomized, open-label RESONATE-2 trial, published in NEJM in 2015.

Results from the RESONATE-2 study showed that ibrutinib significantly prolonged overall survival (OS) (HR=0.16, 95 percent CI 0.05 to 0.56; P=0.001).

Ninety-eight percent of patients were still alive after 2 years, compared to 85% percent for patients randomized to the chlorambucil arm. 

Median progression-free survival (PFS) was not reached for patients receiving ibrutinib versus 18.9 months for those in the chlorambucil arm. This represented a statistically significant 84% reduction in the risk of death or progression in the ibrutinib arm (HR=0.16, 95 percent CI 0.09 to 0.28; P<0.001). 

“Ibrutinib has shown remarkable improvements in overall survival, progression-free survival, and response rates compared with chlorambucil,” said Paolo Ghia, MD, PhD, one of the RESONATE-2 investigators.

The overall safety of ibrutinib in the treatment-naïve CLL patient population was consistent with previously reported studies. 

The most common adverse events for ibrutinib of any grade occurring in 20% or more of the patients were diarrhea (42%), fatigue (30%), cough (22%), and nausea (22%).

“The RESONATE-2 data indicate that ibrutinib can provide a much-needed first line treatment alternative for many patients,” Dr Ghia affirmed.

Ibrutinib is co-developed by Cilag GmbH International, a member of the Janssen Pharmaceutical Companies, and Pharmacyclics LLC, an AbbVie company. Janssen affiliates market ibrutinib in all approved countries except the US. In the US, Janssen Biotech, Inc. and Pharmacyclics co-market it.

Ibrutinib (Imbruvica)
Photo from Janssen Biotech

The European Commission (EC) has broadened the indication for ibrutinib (Imbruvica) to include newly diagnosed patients with chronic lymphocytic leukemia (CLL).

The drug had already been approved in the European Union to treat adults with CLL who have received at least one prior therapy and adults with previously untreated CLL who have 17p deletion or TP53 mutation and are unsuitable for chemo-immunotherapy. 

Ibrutinib is now approved for all patients with CLL.

The EC is following the recommendation of the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP), which had previously sent its endorsement to the EC.

This approval also follows the decision by the US Food and Drug Administration in March to approve the expanded use of ibrutinib capsules for treatment-naïve patients with CLL.

Ibrutinib is also approved to treat adults with relapsed or refractory mantle cell lymphoma, adults with Waldenström’s macroglobulinemia who have received at least one prior therapy, and previously untreated adults with Waldenström’s macroglobulinemia who are unsuitable for chemo-immunotherapy.

RESONATE-2 trial

The expanded ibrutinib indication is based on data from the phase 3, randomized, open-label RESONATE-2 trial, published in NEJM in 2015.

Results from the RESONATE-2 study showed that ibrutinib significantly prolonged overall survival (OS) (HR=0.16, 95 percent CI 0.05 to 0.56; P=0.001).

Ninety-eight percent of patients were still alive after 2 years, compared to 85% percent for patients randomized to the chlorambucil arm. 

Median progression-free survival (PFS) was not reached for patients receiving ibrutinib versus 18.9 months for those in the chlorambucil arm. This represented a statistically significant 84% reduction in the risk of death or progression in the ibrutinib arm (HR=0.16, 95 percent CI 0.09 to 0.28; P<0.001). 

“Ibrutinib has shown remarkable improvements in overall survival, progression-free survival, and response rates compared with chlorambucil,” said Paolo Ghia, MD, PhD, one of the RESONATE-2 investigators.

The overall safety of ibrutinib in the treatment-naïve CLL patient population was consistent with previously reported studies. 

The most common adverse events for ibrutinib of any grade occurring in 20% or more of the patients were diarrhea (42%), fatigue (30%), cough (22%), and nausea (22%).

“The RESONATE-2 data indicate that ibrutinib can provide a much-needed first line treatment alternative for many patients,” Dr Ghia affirmed.

Ibrutinib is co-developed by Cilag GmbH International, a member of the Janssen Pharmaceutical Companies, and Pharmacyclics LLC, an AbbVie company. Janssen affiliates market ibrutinib in all approved countries except the US. In the US, Janssen Biotech, Inc. and Pharmacyclics co-market it.

Plasmodium parasite
invading an RBC
Credit: St Jude Children's
Research Hospital

Two new anti-malaria drug candidates with different mechanisms of action—a pyrazoleamide and a spiroindolone—promote an influx of sodium ions into Plasmodium parasites that have invaded red blood cells and multiply there.

Within minutes, the increase in sodium kills the parasites, investigators believe, by changing its outer membrane and promoting division before its genome has been replicated.

Akhil Vaidya, PhD, of Drexel University College of Medicine in Philadelphia, and members of the research team published details of their findings in PLOS Pathogens.

The Plasmodium plasma membrane contains very low levels of cholesterol, which is a major lipid component of most other cell membranes. 

Saponin, a detergent that can dissolve cholesterol-containing membranes, dissolves red blood cells infected by Plasmodium and releases intact parasites into the bloodstream. The detergent is unable to destroy the parasites because their membranes have low cholesterol content.

However, when researchers exposed the parasite cell membranes to the 2 drugs, they became permeable by saponin. The researchers deemed this to be a function of the increased amount of cholesterol incorporated into the parasite membrane.

“We believe that the cholesterol makes the parasite rigid, and then the parasite can no longer pass through very small spaces in the bloodstream,” Dr Vaidya said. The parasite cannot continue its lifecycle if it cannot enter red blood cells.

Researchers also discovered that when drug exposure is short, the changes in membrane composition are reversible. The parasites regain their resistance to saponin most likely because the additional membrane cholesterol washes off.

After 2 hours of treatment with either drug, many of the parasites had fragmented nuclei and interior membranes. Researchers did not observe any sign of multiplication of the parasite genome, which is necessary to create daughter cells and precedes other cell division events.

The researchers were surprised by the findings. They had assumed that the spiroindolone, KAE609 (cipargamin), which is being investigated in clinical trials, killed parasites through a different mechanism. 

The investigators maintain that by understanding exactly how new drug candidates stop malaria, they will learn more about the parasite’s vulnerabilities and be able to determine the origin of drug resistance as soon as it arises. 

“We want to find the best ways to keep new drugs effective as long as we can,” Dr Vaidya said.

This study was funded by National Institutes of Health Grant R01-AI98413 and Medicines for Malaria Venture Grant MMV/08/0027.

Plasmodium parasite
invading an RBC
Credit: St Jude Children's
Research Hospital

Two new anti-malaria drug candidates with different mechanisms of action—a pyrazoleamide and a spiroindolone—promote an influx of sodium ions into Plasmodium parasites that have invaded red blood cells and multiply there.

Within minutes, the increase in sodium kills the parasites, investigators believe, by changing its outer membrane and promoting division before its genome has been replicated.

Akhil Vaidya, PhD, of Drexel University College of Medicine in Philadelphia, and members of the research team published details of their findings in PLOS Pathogens.

The Plasmodium plasma membrane contains very low levels of cholesterol, which is a major lipid component of most other cell membranes. 

Saponin, a detergent that can dissolve cholesterol-containing membranes, dissolves red blood cells infected by Plasmodium and releases intact parasites into the bloodstream. The detergent is unable to destroy the parasites because their membranes have low cholesterol content.

However, when researchers exposed the parasite cell membranes to the 2 drugs, they became permeable by saponin. The researchers deemed this to be a function of the increased amount of cholesterol incorporated into the parasite membrane.

“We believe that the cholesterol makes the parasite rigid, and then the parasite can no longer pass through very small spaces in the bloodstream,” Dr Vaidya said. The parasite cannot continue its lifecycle if it cannot enter red blood cells.

Researchers also discovered that when drug exposure is short, the changes in membrane composition are reversible. The parasites regain their resistance to saponin most likely because the additional membrane cholesterol washes off.

After 2 hours of treatment with either drug, many of the parasites had fragmented nuclei and interior membranes. Researchers did not observe any sign of multiplication of the parasite genome, which is necessary to create daughter cells and precedes other cell division events.

The researchers were surprised by the findings. They had assumed that the spiroindolone, KAE609 (cipargamin), which is being investigated in clinical trials, killed parasites through a different mechanism. 

The investigators maintain that by understanding exactly how new drug candidates stop malaria, they will learn more about the parasite’s vulnerabilities and be able to determine the origin of drug resistance as soon as it arises. 

“We want to find the best ways to keep new drugs effective as long as we can,” Dr Vaidya said.

This study was funded by National Institutes of Health Grant R01-AI98413 and Medicines for Malaria Venture Grant MMV/08/0027.

Plasmodium parasite
invading an RBC
Credit: St Jude Children's
Research Hospital

Two new anti-malaria drug candidates with different mechanisms of action—a pyrazoleamide and a spiroindolone—promote an influx of sodium ions into Plasmodium parasites that have invaded red blood cells and multiply there.

Within minutes, the increase in sodium kills the parasites, investigators believe, by changing its outer membrane and promoting division before its genome has been replicated.

Akhil Vaidya, PhD, of Drexel University College of Medicine in Philadelphia, and members of the research team published details of their findings in PLOS Pathogens.

The Plasmodium plasma membrane contains very low levels of cholesterol, which is a major lipid component of most other cell membranes. 

Saponin, a detergent that can dissolve cholesterol-containing membranes, dissolves red blood cells infected by Plasmodium and releases intact parasites into the bloodstream. The detergent is unable to destroy the parasites because their membranes have low cholesterol content.

However, when researchers exposed the parasite cell membranes to the 2 drugs, they became permeable by saponin. The researchers deemed this to be a function of the increased amount of cholesterol incorporated into the parasite membrane.

“We believe that the cholesterol makes the parasite rigid, and then the parasite can no longer pass through very small spaces in the bloodstream,” Dr Vaidya said. The parasite cannot continue its lifecycle if it cannot enter red blood cells.

Researchers also discovered that when drug exposure is short, the changes in membrane composition are reversible. The parasites regain their resistance to saponin most likely because the additional membrane cholesterol washes off.

After 2 hours of treatment with either drug, many of the parasites had fragmented nuclei and interior membranes. Researchers did not observe any sign of multiplication of the parasite genome, which is necessary to create daughter cells and precedes other cell division events.

The researchers were surprised by the findings. They had assumed that the spiroindolone, KAE609 (cipargamin), which is being investigated in clinical trials, killed parasites through a different mechanism. 

The investigators maintain that by understanding exactly how new drug candidates stop malaria, they will learn more about the parasite’s vulnerabilities and be able to determine the origin of drug resistance as soon as it arises. 

“We want to find the best ways to keep new drugs effective as long as we can,” Dr Vaidya said.

This study was funded by National Institutes of Health Grant R01-AI98413 and Medicines for Malaria Venture Grant MMV/08/0027.