Doug Brunk

DENVER – Moderate alcohol consumption among renal transplant recipients is inversely associated with posttransplant diabetes and all-cause mortality, results from a large single-center study showed.

The finding contradicts the notion that renal transplant recipients should refrain from alcohol use because of possible interaction with their immunosuppressive drugs, lead investigator Dorien M. Zelle said in an interview during a poster session at the annual meeting of the American Society of Nephrology.

"After renal transplantation, patients have a lot of restrictions," said Ms. Zelle, a PhD candidate at University Medical Center Groningen, The Netherlands. "Doctors advise them not to smoke, and they have to take a lot of medications. We should not advise them against moderate alcohol consumption, because we have shown that nondrinkers are doing worse than moderate drinkers after transplantation."

She went on to note that the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Care of Kidney Transplant Recipients does mention specific alcohol restrictions for kidney transplant patients.

Ms. Zelle and her associates studied 600 renal transplant recipients who visited the medical center’s outpatient clinic between 2001 and 2003 and were at least 1 year post transplant. They filled out self-report questionnaires about their alcohol use and the researchers recorded mortality and graft failure until May 2009. Study participants were classified into one of four groups: abstainers, sporadic drinkers, moderate drinkers (range of 1 unit per week to 3 units per day), and heavy drinkers (4 or more units per day).

At baseline, the mean age of the 600 patients was 51 years and 12% had posttransplant diabetes. Nearly half (288, or 48%) were abstainers, 94 (16%) were sporadic drinkers, 210 (35%) were moderate drinkers, and 8 (1%) were heavy drinkers.

Ms. Zelle reported that during a median follow-up of 7 years, moderate drinkers had a 67% lower risk for diabetes compared with respondents in the other groups (OR = 0.33). In addition, 33 (15.7%) of the moderate drinkers died, compared with 75 (26%) of the abstainers, 23 (24.5%) of the sporadic drinkers, and 2 (25%) of the heavy drinkers.

Univariate Cox regression analysis revealed that moderate drinkers were 44% less likely to die after transplantation compared with respondents in the other groups (HR = 0.56). Adjustment for potential confounders including diabetes and smoking did not change this association.

Ms. Zelle acknowledged certain limitations of the study, including its single center design and the fact that alcohol consumption was measured at a single point in time. "It could be that some patients started drinking more or quit drinking during the course of the study," she said.

Ms. Zelle said that she had no relevant financial disclosures to make.

DENVER – Moderate alcohol consumption among renal transplant recipients is inversely associated with posttransplant diabetes and all-cause mortality, results from a large single-center study showed.

The finding contradicts the notion that renal transplant recipients should refrain from alcohol use because of possible interaction with their immunosuppressive drugs, lead investigator Dorien M. Zelle said in an interview during a poster session at the annual meeting of the American Society of Nephrology.

"After renal transplantation, patients have a lot of restrictions," said Ms. Zelle, a PhD candidate at University Medical Center Groningen, The Netherlands. "Doctors advise them not to smoke, and they have to take a lot of medications. We should not advise them against moderate alcohol consumption, because we have shown that nondrinkers are doing worse than moderate drinkers after transplantation."

She went on to note that the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Care of Kidney Transplant Recipients does mention specific alcohol restrictions for kidney transplant patients.

Ms. Zelle and her associates studied 600 renal transplant recipients who visited the medical center’s outpatient clinic between 2001 and 2003 and were at least 1 year post transplant. They filled out self-report questionnaires about their alcohol use and the researchers recorded mortality and graft failure until May 2009. Study participants were classified into one of four groups: abstainers, sporadic drinkers, moderate drinkers (range of 1 unit per week to 3 units per day), and heavy drinkers (4 or more units per day).

At baseline, the mean age of the 600 patients was 51 years and 12% had posttransplant diabetes. Nearly half (288, or 48%) were abstainers, 94 (16%) were sporadic drinkers, 210 (35%) were moderate drinkers, and 8 (1%) were heavy drinkers.

Ms. Zelle reported that during a median follow-up of 7 years, moderate drinkers had a 67% lower risk for diabetes compared with respondents in the other groups (OR = 0.33). In addition, 33 (15.7%) of the moderate drinkers died, compared with 75 (26%) of the abstainers, 23 (24.5%) of the sporadic drinkers, and 2 (25%) of the heavy drinkers.

Univariate Cox regression analysis revealed that moderate drinkers were 44% less likely to die after transplantation compared with respondents in the other groups (HR = 0.56). Adjustment for potential confounders including diabetes and smoking did not change this association.

Ms. Zelle acknowledged certain limitations of the study, including its single center design and the fact that alcohol consumption was measured at a single point in time. "It could be that some patients started drinking more or quit drinking during the course of the study," she said.

Ms. Zelle said that she had no relevant financial disclosures to make.

DENVER – Moderate alcohol consumption among renal transplant recipients is inversely associated with posttransplant diabetes and all-cause mortality, results from a large single-center study showed.

The finding contradicts the notion that renal transplant recipients should refrain from alcohol use because of possible interaction with their immunosuppressive drugs, lead investigator Dorien M. Zelle said in an interview during a poster session at the annual meeting of the American Society of Nephrology.

"After renal transplantation, patients have a lot of restrictions," said Ms. Zelle, a PhD candidate at University Medical Center Groningen, The Netherlands. "Doctors advise them not to smoke, and they have to take a lot of medications. We should not advise them against moderate alcohol consumption, because we have shown that nondrinkers are doing worse than moderate drinkers after transplantation."

She went on to note that the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Care of Kidney Transplant Recipients does mention specific alcohol restrictions for kidney transplant patients.

Ms. Zelle and her associates studied 600 renal transplant recipients who visited the medical center’s outpatient clinic between 2001 and 2003 and were at least 1 year post transplant. They filled out self-report questionnaires about their alcohol use and the researchers recorded mortality and graft failure until May 2009. Study participants were classified into one of four groups: abstainers, sporadic drinkers, moderate drinkers (range of 1 unit per week to 3 units per day), and heavy drinkers (4 or more units per day).

At baseline, the mean age of the 600 patients was 51 years and 12% had posttransplant diabetes. Nearly half (288, or 48%) were abstainers, 94 (16%) were sporadic drinkers, 210 (35%) were moderate drinkers, and 8 (1%) were heavy drinkers.

Ms. Zelle reported that during a median follow-up of 7 years, moderate drinkers had a 67% lower risk for diabetes compared with respondents in the other groups (OR = 0.33). In addition, 33 (15.7%) of the moderate drinkers died, compared with 75 (26%) of the abstainers, 23 (24.5%) of the sporadic drinkers, and 2 (25%) of the heavy drinkers.

Univariate Cox regression analysis revealed that moderate drinkers were 44% less likely to die after transplantation compared with respondents in the other groups (HR = 0.56). Adjustment for potential confounders including diabetes and smoking did not change this association.

Ms. Zelle acknowledged certain limitations of the study, including its single center design and the fact that alcohol consumption was measured at a single point in time. "It could be that some patients started drinking more or quit drinking during the course of the study," she said.

Ms. Zelle said that she had no relevant financial disclosures to make.

SAN DIEGO - Adding a simple question to the daily ICU checklist about handwashing before touching patients significantly improved handwashing compliance and was associated with a decreased rate of central line-associated bloodstream infections in a surgical intensive care unit over the course of 6 months, according to a presentation at the annual congress of the Society of Critical Care Medicine.

"If you look at how people address hand hygiene compliance overall, most of the time it's with fairly elaborate and expensive educational and marketing campaigns," Dr. Jeremy Pamplin said in an interview after the study was presented during a poster session at the congress. "Inevitably, you improve hand hygiene compliance for a while. Then the campaign goes away and you start to have fading of the compliance."

As part of a process improvement project, Dr. Pamplin, medical codirector of the 20-bed surgical/trauma ICU at Brooke Army Medical Center, Fort Sam Houston, Tex., and his associates added the following question to their daily ICU checklist: "Has anyone seen anyone else touch the patient without washing their hands in the past 24 hours?" The question was asked during multidisciplinary ICU rounds for every patient, and only "yes" or "no" answers were allowed.

If respondents answered "yes," they were asked to provide the name of the offender, which was recorded. Compliance was measured by a third-party observer and was defined as washing hands or using hand sanitizer prior to touching a patient or the patient's immediate surroundings.

Dr. Pamplin and his associates collected data for 3 months before and 3 months after this question was added to the ICU checklist. Over that period, the rate of handwashing compliance significantly increased from 69% to 89%, while the rate of central line-associated bloodstream infections decreased from 13.7/1,000 central line days to 2.7/1,000 central line days, an improvement that did not reach statistical significance.

"Before we introduced this question to our checklist, it was very rare for a provider to tell another provider, 'Hey, I didn't see you wash your hands," Dr. Pamplin said. "After we introduced this question, people started doing it because we gave leadership and emphasis to it."

This resulted in a change of culture, he continued, "so if nurses, residents, or technicians saw someone walk into the room without washing their hands, they would stop them and say, 'Hang on a second; you didn't wash your hands.' Everyone knows that hand hygiene is an important part of infection control. The hard part is remembering to do it. It's a rare circumstance that someone gets upset by another health care provider who says, 'Hey, you forgot to wash your hands.' Because we have talked about hand hygiene compliance on rounds as a team, it has elevated that component of infection control so that everyone recognizes it as being important."

Dr. Pamplin said that he had no relevant financial disclosures to make.

SAN DIEGO - Adding a simple question to the daily ICU checklist about handwashing before touching patients significantly improved handwashing compliance and was associated with a decreased rate of central line-associated bloodstream infections in a surgical intensive care unit over the course of 6 months, according to a presentation at the annual congress of the Society of Critical Care Medicine.

"If you look at how people address hand hygiene compliance overall, most of the time it's with fairly elaborate and expensive educational and marketing campaigns," Dr. Jeremy Pamplin said in an interview after the study was presented during a poster session at the congress. "Inevitably, you improve hand hygiene compliance for a while. Then the campaign goes away and you start to have fading of the compliance."

As part of a process improvement project, Dr. Pamplin, medical codirector of the 20-bed surgical/trauma ICU at Brooke Army Medical Center, Fort Sam Houston, Tex., and his associates added the following question to their daily ICU checklist: "Has anyone seen anyone else touch the patient without washing their hands in the past 24 hours?" The question was asked during multidisciplinary ICU rounds for every patient, and only "yes" or "no" answers were allowed.

If respondents answered "yes," they were asked to provide the name of the offender, which was recorded. Compliance was measured by a third-party observer and was defined as washing hands or using hand sanitizer prior to touching a patient or the patient's immediate surroundings.

Dr. Pamplin and his associates collected data for 3 months before and 3 months after this question was added to the ICU checklist. Over that period, the rate of handwashing compliance significantly increased from 69% to 89%, while the rate of central line-associated bloodstream infections decreased from 13.7/1,000 central line days to 2.7/1,000 central line days, an improvement that did not reach statistical significance.

"Before we introduced this question to our checklist, it was very rare for a provider to tell another provider, 'Hey, I didn't see you wash your hands," Dr. Pamplin said. "After we introduced this question, people started doing it because we gave leadership and emphasis to it."

This resulted in a change of culture, he continued, "so if nurses, residents, or technicians saw someone walk into the room without washing their hands, they would stop them and say, 'Hang on a second; you didn't wash your hands.' Everyone knows that hand hygiene is an important part of infection control. The hard part is remembering to do it. It's a rare circumstance that someone gets upset by another health care provider who says, 'Hey, you forgot to wash your hands.' Because we have talked about hand hygiene compliance on rounds as a team, it has elevated that component of infection control so that everyone recognizes it as being important."

Dr. Pamplin said that he had no relevant financial disclosures to make.

SAN DIEGO - Adding a simple question to the daily ICU checklist about handwashing before touching patients significantly improved handwashing compliance and was associated with a decreased rate of central line-associated bloodstream infections in a surgical intensive care unit over the course of 6 months, according to a presentation at the annual congress of the Society of Critical Care Medicine.

"If you look at how people address hand hygiene compliance overall, most of the time it's with fairly elaborate and expensive educational and marketing campaigns," Dr. Jeremy Pamplin said in an interview after the study was presented during a poster session at the congress. "Inevitably, you improve hand hygiene compliance for a while. Then the campaign goes away and you start to have fading of the compliance."

As part of a process improvement project, Dr. Pamplin, medical codirector of the 20-bed surgical/trauma ICU at Brooke Army Medical Center, Fort Sam Houston, Tex., and his associates added the following question to their daily ICU checklist: "Has anyone seen anyone else touch the patient without washing their hands in the past 24 hours?" The question was asked during multidisciplinary ICU rounds for every patient, and only "yes" or "no" answers were allowed.

If respondents answered "yes," they were asked to provide the name of the offender, which was recorded. Compliance was measured by a third-party observer and was defined as washing hands or using hand sanitizer prior to touching a patient or the patient's immediate surroundings.

Dr. Pamplin and his associates collected data for 3 months before and 3 months after this question was added to the ICU checklist. Over that period, the rate of handwashing compliance significantly increased from 69% to 89%, while the rate of central line-associated bloodstream infections decreased from 13.7/1,000 central line days to 2.7/1,000 central line days, an improvement that did not reach statistical significance.

"Before we introduced this question to our checklist, it was very rare for a provider to tell another provider, 'Hey, I didn't see you wash your hands," Dr. Pamplin said. "After we introduced this question, people started doing it because we gave leadership and emphasis to it."

This resulted in a change of culture, he continued, "so if nurses, residents, or technicians saw someone walk into the room without washing their hands, they would stop them and say, 'Hang on a second; you didn't wash your hands.' Everyone knows that hand hygiene is an important part of infection control. The hard part is remembering to do it. It's a rare circumstance that someone gets upset by another health care provider who says, 'Hey, you forgot to wash your hands.' Because we have talked about hand hygiene compliance on rounds as a team, it has elevated that component of infection control so that everyone recognizes it as being important."

Dr. Pamplin said that he had no relevant financial disclosures to make.

Major Finding: The 1-year survival rate improved significantly from 76% in the original HeartMate II trial to 85% in a commercial use trial of the device.

Data Source: A study of 1,496 patients at 83 centers who received the device between April 2008 and September 2010 for bridge to transplantation.

Disclosures: Dr. John disclosed that he received a research grant from Thoratec Corp. to conduct the study. One of the study investigators is employed by the company.

SAN DIEGO – Survival rates of patients implanted with the HeartMate II ventricular assist device have improved significantly, according to a long-term multicenter analysis designed to compare outcomes from the time of the clinical trial to those in the post–Food and Drug Administration approval period.

Excellent outcomes have been maintained and the incidence of adverse events has trended downward with the HeartMate II, a continuous-flow left ventricular assist device (LVAD) for bridge to heart transplantation, Dr. Ranjit John said at the meeting.

A multicenter trial of the HeartMate II, manufactured by Thoratec Corp., was conducted from 2005 to 2008 and led to FDA clearance of the device for bridge to transplantation. Since FDA clearance in April 2008, more than 1,400 additional patients implanted with the device for bridge to transplantation have been tracked by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), which is funded by the National Institutes of Health.

The HeartMate II, also cleared for destination therapy, has been implanted in more than 6,000 patients worldwide, with more than 5,000 patient years of support, according to Dr. John, of the department of cardiothoracic surgery at the University of Minnesota, Minneapolis.

The original trial of the device enrolled 486 bridge to transplantation patients at 36 centers in North America between March 2005 and April 2008. The post-trial commercial use study enrolled 1,496 patients at 83 centers between April 2008 and September 2010. The study's primary end point was survival. Secondary end points included frequency of adverse events and complications, functional status as assessed by the 6-minute walk, and quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire in the original trial and the EuroQol (EQ-5D) instrument in the post trial.

Dr. John reported that the 1-year survival rate improved significantly from 76% in the original trial to 85% in post trial. “With every era of the trial, there was a stepwise incremental improvement in survival, probably from all lessons learned from the early phases of the original trial,” he commented.

The percentage of patients transplanted by 1 year decreased from 48% in the original trial to 39% in the post trial, while the percentage of patients receiving ongoing support increased from 32% in the original trial to 45% in the post trial.

The overall incidences of bleeding and infection in the post trial were 36% and 38%, respectively. Specifically, the incidence of bleeding requiring surgical reexploration was 7%, while the incidence of driveline infections was 13%.

The incidence of adverse events trended downward in the post trial, compared with the original trial. For example, the incidence of bleeding requiring reexploration was 21% in the original trial vs. 7% in the post-trial group. Similar declines were seen in the incidence of percutaneous lead infections (20% vs. 13%, respectively), right heart failure requiring right ventricular assist device (7% vs. 1%), and the need for device replacement (5% vs. 1%).

At baseline, only 13% of patients in the original trial and 16% of patients in the post trial could complete the 6-minute walk test. At 6 months, the proportion of patients who could complete the test improved to 92% and 94%, respectively.

Dr. John also reported that quality of life measures improved in up to 6 months in the original trial and up to 12 months in the post trial.

The invited discussant, Dr. Michael A. Acker, said that the results of the post trial demonstrate “that new VAD technology that utilizes continuous flow – a disruptive concept compared to pulsatile flow – can be taught, along with appropriate patient selection, and can be disseminated to a broad range of clinical centers. If similar successful dissemination occurs after the destination therapy approval, small continuous-flow pumps will constitute a paradigm shift for the treatment of end-stage heart failure.”

Dr. Acker, who heads the cardiovascular surgery division at the University of Pennsylvania Medical Center, Philadelphia, noted that the trial also demonstrates “that mandatory prospective databases such as INTERMACS are essential for monitoring outcomes and providing feedback needed to improve results.”

'With every era of the trial, there was a stepwise incremental improvement in survival.'

Source DR. JOHN

Major Finding: The 1-year survival rate improved significantly from 76% in the original HeartMate II trial to 85% in a commercial use trial of the device.

Data Source: A study of 1,496 patients at 83 centers who received the device between April 2008 and September 2010 for bridge to transplantation.

Disclosures: Dr. John disclosed that he received a research grant from Thoratec Corp. to conduct the study. One of the study investigators is employed by the company.

SAN DIEGO – Survival rates of patients implanted with the HeartMate II ventricular assist device have improved significantly, according to a long-term multicenter analysis designed to compare outcomes from the time of the clinical trial to those in the post–Food and Drug Administration approval period.

Excellent outcomes have been maintained and the incidence of adverse events has trended downward with the HeartMate II, a continuous-flow left ventricular assist device (LVAD) for bridge to heart transplantation, Dr. Ranjit John said at the meeting.

A multicenter trial of the HeartMate II, manufactured by Thoratec Corp., was conducted from 2005 to 2008 and led to FDA clearance of the device for bridge to transplantation. Since FDA clearance in April 2008, more than 1,400 additional patients implanted with the device for bridge to transplantation have been tracked by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), which is funded by the National Institutes of Health.

The HeartMate II, also cleared for destination therapy, has been implanted in more than 6,000 patients worldwide, with more than 5,000 patient years of support, according to Dr. John, of the department of cardiothoracic surgery at the University of Minnesota, Minneapolis.

The original trial of the device enrolled 486 bridge to transplantation patients at 36 centers in North America between March 2005 and April 2008. The post-trial commercial use study enrolled 1,496 patients at 83 centers between April 2008 and September 2010. The study's primary end point was survival. Secondary end points included frequency of adverse events and complications, functional status as assessed by the 6-minute walk, and quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire in the original trial and the EuroQol (EQ-5D) instrument in the post trial.

Dr. John reported that the 1-year survival rate improved significantly from 76% in the original trial to 85% in post trial. “With every era of the trial, there was a stepwise incremental improvement in survival, probably from all lessons learned from the early phases of the original trial,” he commented.

The percentage of patients transplanted by 1 year decreased from 48% in the original trial to 39% in the post trial, while the percentage of patients receiving ongoing support increased from 32% in the original trial to 45% in the post trial.

The overall incidences of bleeding and infection in the post trial were 36% and 38%, respectively. Specifically, the incidence of bleeding requiring surgical reexploration was 7%, while the incidence of driveline infections was 13%.

The incidence of adverse events trended downward in the post trial, compared with the original trial. For example, the incidence of bleeding requiring reexploration was 21% in the original trial vs. 7% in the post-trial group. Similar declines were seen in the incidence of percutaneous lead infections (20% vs. 13%, respectively), right heart failure requiring right ventricular assist device (7% vs. 1%), and the need for device replacement (5% vs. 1%).

At baseline, only 13% of patients in the original trial and 16% of patients in the post trial could complete the 6-minute walk test. At 6 months, the proportion of patients who could complete the test improved to 92% and 94%, respectively.

Dr. John also reported that quality of life measures improved in up to 6 months in the original trial and up to 12 months in the post trial.

The invited discussant, Dr. Michael A. Acker, said that the results of the post trial demonstrate “that new VAD technology that utilizes continuous flow – a disruptive concept compared to pulsatile flow – can be taught, along with appropriate patient selection, and can be disseminated to a broad range of clinical centers. If similar successful dissemination occurs after the destination therapy approval, small continuous-flow pumps will constitute a paradigm shift for the treatment of end-stage heart failure.”

Dr. Acker, who heads the cardiovascular surgery division at the University of Pennsylvania Medical Center, Philadelphia, noted that the trial also demonstrates “that mandatory prospective databases such as INTERMACS are essential for monitoring outcomes and providing feedback needed to improve results.”

'With every era of the trial, there was a stepwise incremental improvement in survival.'

Source DR. JOHN

Major Finding: The 1-year survival rate improved significantly from 76% in the original HeartMate II trial to 85% in a commercial use trial of the device.

Data Source: A study of 1,496 patients at 83 centers who received the device between April 2008 and September 2010 for bridge to transplantation.

Disclosures: Dr. John disclosed that he received a research grant from Thoratec Corp. to conduct the study. One of the study investigators is employed by the company.

SAN DIEGO – Survival rates of patients implanted with the HeartMate II ventricular assist device have improved significantly, according to a long-term multicenter analysis designed to compare outcomes from the time of the clinical trial to those in the post–Food and Drug Administration approval period.

Excellent outcomes have been maintained and the incidence of adverse events has trended downward with the HeartMate II, a continuous-flow left ventricular assist device (LVAD) for bridge to heart transplantation, Dr. Ranjit John said at the meeting.

A multicenter trial of the HeartMate II, manufactured by Thoratec Corp., was conducted from 2005 to 2008 and led to FDA clearance of the device for bridge to transplantation. Since FDA clearance in April 2008, more than 1,400 additional patients implanted with the device for bridge to transplantation have been tracked by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), which is funded by the National Institutes of Health.

The HeartMate II, also cleared for destination therapy, has been implanted in more than 6,000 patients worldwide, with more than 5,000 patient years of support, according to Dr. John, of the department of cardiothoracic surgery at the University of Minnesota, Minneapolis.

The original trial of the device enrolled 486 bridge to transplantation patients at 36 centers in North America between March 2005 and April 2008. The post-trial commercial use study enrolled 1,496 patients at 83 centers between April 2008 and September 2010. The study's primary end point was survival. Secondary end points included frequency of adverse events and complications, functional status as assessed by the 6-minute walk, and quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire in the original trial and the EuroQol (EQ-5D) instrument in the post trial.

Dr. John reported that the 1-year survival rate improved significantly from 76% in the original trial to 85% in post trial. “With every era of the trial, there was a stepwise incremental improvement in survival, probably from all lessons learned from the early phases of the original trial,” he commented.

The percentage of patients transplanted by 1 year decreased from 48% in the original trial to 39% in the post trial, while the percentage of patients receiving ongoing support increased from 32% in the original trial to 45% in the post trial.

The overall incidences of bleeding and infection in the post trial were 36% and 38%, respectively. Specifically, the incidence of bleeding requiring surgical reexploration was 7%, while the incidence of driveline infections was 13%.

The incidence of adverse events trended downward in the post trial, compared with the original trial. For example, the incidence of bleeding requiring reexploration was 21% in the original trial vs. 7% in the post-trial group. Similar declines were seen in the incidence of percutaneous lead infections (20% vs. 13%, respectively), right heart failure requiring right ventricular assist device (7% vs. 1%), and the need for device replacement (5% vs. 1%).

At baseline, only 13% of patients in the original trial and 16% of patients in the post trial could complete the 6-minute walk test. At 6 months, the proportion of patients who could complete the test improved to 92% and 94%, respectively.

Dr. John also reported that quality of life measures improved in up to 6 months in the original trial and up to 12 months in the post trial.

The invited discussant, Dr. Michael A. Acker, said that the results of the post trial demonstrate “that new VAD technology that utilizes continuous flow – a disruptive concept compared to pulsatile flow – can be taught, along with appropriate patient selection, and can be disseminated to a broad range of clinical centers. If similar successful dissemination occurs after the destination therapy approval, small continuous-flow pumps will constitute a paradigm shift for the treatment of end-stage heart failure.”

Dr. Acker, who heads the cardiovascular surgery division at the University of Pennsylvania Medical Center, Philadelphia, noted that the trial also demonstrates “that mandatory prospective databases such as INTERMACS are essential for monitoring outcomes and providing feedback needed to improve results.”

'With every era of the trial, there was a stepwise incremental improvement in survival.'

Source DR. JOHN

SAN DIEGO – Results from the latest workforce survey conducted by the Thoracic Surgery Residents Association reveal some troubling trends.

Nearly one-third of respondents who identified themselves as seeking employment (31%) reported having no job offers 10-12 weeks before completing their residency, and 17% reported education-related debt exceeding $200,000.

"We have to anticipate that continued unease regarding job availability, combined with increasing debt burden, may be a concern for potential trainees, and a possible deterrent or barrier to their matriculation into cardiothoracic surgery," Dr. Inderpal S. Sarkaria said at the annual meeting of the Society of Thoracic Surgeons.

At the same time, however, 65% of survey respondents said that they would positively recommend cardiothoracic surgery as a career to potential applicants. "I believe that the attraction and thrill of what we do as cardiothoracic surgeons is real and will always be an advantage to our specialty in attracting potential trainees," said Dr. Sarkaria, a cardiothoracic surgeon at Memorial Sloan-Kettering Cancer Center, New York.

First administered in 2006, the Thoracic Surgery Residents Association (TSRA) Workforce Survey became mandatory in 2007 as a prerequisite to taking the American Board of Surgery In-Training Examination (ABSITE), which is typically taken during the final 10-12 weeks of cardiothoracic residency. Results from a separate TSRA survey question administered during the 2009 ABSITE identified approximately 11% of general surgery residents anticipating careers in cardiothoracic surgery.

"This is encouraging and has been steady over the past few years, but it’s still far diminished from prior years," Dr. Sarkaria said. "Other surveys from the STS [Society of Thoracic Surgeons] and the American Association of Medical Colleges have identified primary concerns and factors affecting general surgery residents’ choice of specialty, such as job security/availability, ability to balance work and personal life, mentorship, and length of training."

Concerns regarding these decreased matriculation rates, he continued, "are compounded by concerns regarding an anticipated shortage of cardiothoracic surgeons over the next 1-2 decades, in which some have suggested that an additional 100 surgeons per year will need to be trained in order to overcome this."

On behalf of the TSRA executive committee, Dr. Sarkaria presented results from 299 cardiothoracic surgery residents who completed the 2010 survey, which included questions about employment, training experience, education-related debt, and determinants of career choice.

Of the 299 respondents, 228 (76%) were citizens of the United States. The majority (84%) were from 2- or 3-year residency programs, while 9% were from 6-year integrated programs. More than half (69%) were in postgraduate years 6-10.

Nearly one-third of respondents (32%) identified adult cardiac as their primary career of interest, followed by mixed cardiothoracic (23%), general thoracic (22%), congenital (11%), heart failure/lung transplant (5%), aortic (5%), and other (2%).

Among respondents who identified themselves as seeking employment, 45% reported that they had more than two job interviews by the time they completed the survey, 23% had two interviews, 15% had one interview, and 17% had no interviews. In addition, 41% reported that they had two or more firm job offers at the time they completed the survey, 28% had one job offer, and 31% had no job offer.

Dr. Sarkaria reported that there has been a steady increase in reported education-related debt between $150,000 and $200,000, from 12% in 2007 to 16% in 2010. The rate of reported education debt exceeding $200,000 increased more than twofold during the same period, from 8% in 2007 to 17% in 2010. "This may be a pertinent financial barrier or deterrent to potential trainees who are considering careers in cardiothoracic surgery," he commented.

When asked about the adequacy of their residency training, 79%-85% described their current training program as adequate and 39% anticipate additional training, primarily in congenital pediatric surgery or transplant and assisted heart devices.

The survey found that use of the Thoracic Surgery Directors Association (TSDA) curriculum "is sporadic, both on an individual and programmatic level," Dr. Sarkaria said. "When asked about the benefit of the TDSA curriculum as an adjunct to their own educational clinical curriculums, 55% say that it is a useful adjunct, while the rest are uncertain of the benefit. I think this shows an opportunity for expansion upon the innovative foundation of the TSDA curriculum to create an improved, uniform, easily accessible, and relevant central repository of knowledge."

When asked about their primary determinants in deciding on a career in cardiothoracic surgery, types of cases and mentorship were the most important factors cited (41% and 32%, respectively).

When asked about when their choice of cardiothoracic surgery career was made – before, during, or after medical school (in general surgery residency) – no time point stood out. "All of these time points represent opportunities for us to improve our identification and mentorship of potential trainees, and provide the curricular flexibility allowing us to matriculate them into cardiothoracic residencies at these various educational stages," Dr. Sarkaria said.

He acknowledged certain limitations of the study, including its self-reported design. "There can certainly be variable interpretation of the questions by residents," he said. "There can also be situational/circumstantial bias at the time the resident is taking the thoracic in-service exam."

Dr. Sarkaria said that he had no relevant financial disclosures.

SAN DIEGO – Results from the latest workforce survey conducted by the Thoracic Surgery Residents Association reveal some troubling trends.

Nearly one-third of respondents who identified themselves as seeking employment (31%) reported having no job offers 10-12 weeks before completing their residency, and 17% reported education-related debt exceeding $200,000.

"We have to anticipate that continued unease regarding job availability, combined with increasing debt burden, may be a concern for potential trainees, and a possible deterrent or barrier to their matriculation into cardiothoracic surgery," Dr. Inderpal S. Sarkaria said at the annual meeting of the Society of Thoracic Surgeons.

At the same time, however, 65% of survey respondents said that they would positively recommend cardiothoracic surgery as a career to potential applicants. "I believe that the attraction and thrill of what we do as cardiothoracic surgeons is real and will always be an advantage to our specialty in attracting potential trainees," said Dr. Sarkaria, a cardiothoracic surgeon at Memorial Sloan-Kettering Cancer Center, New York.

First administered in 2006, the Thoracic Surgery Residents Association (TSRA) Workforce Survey became mandatory in 2007 as a prerequisite to taking the American Board of Surgery In-Training Examination (ABSITE), which is typically taken during the final 10-12 weeks of cardiothoracic residency. Results from a separate TSRA survey question administered during the 2009 ABSITE identified approximately 11% of general surgery residents anticipating careers in cardiothoracic surgery.

"This is encouraging and has been steady over the past few years, but it’s still far diminished from prior years," Dr. Sarkaria said. "Other surveys from the STS [Society of Thoracic Surgeons] and the American Association of Medical Colleges have identified primary concerns and factors affecting general surgery residents’ choice of specialty, such as job security/availability, ability to balance work and personal life, mentorship, and length of training."

Concerns regarding these decreased matriculation rates, he continued, "are compounded by concerns regarding an anticipated shortage of cardiothoracic surgeons over the next 1-2 decades, in which some have suggested that an additional 100 surgeons per year will need to be trained in order to overcome this."

On behalf of the TSRA executive committee, Dr. Sarkaria presented results from 299 cardiothoracic surgery residents who completed the 2010 survey, which included questions about employment, training experience, education-related debt, and determinants of career choice.

Of the 299 respondents, 228 (76%) were citizens of the United States. The majority (84%) were from 2- or 3-year residency programs, while 9% were from 6-year integrated programs. More than half (69%) were in postgraduate years 6-10.

Nearly one-third of respondents (32%) identified adult cardiac as their primary career of interest, followed by mixed cardiothoracic (23%), general thoracic (22%), congenital (11%), heart failure/lung transplant (5%), aortic (5%), and other (2%).

Among respondents who identified themselves as seeking employment, 45% reported that they had more than two job interviews by the time they completed the survey, 23% had two interviews, 15% had one interview, and 17% had no interviews. In addition, 41% reported that they had two or more firm job offers at the time they completed the survey, 28% had one job offer, and 31% had no job offer.

Dr. Sarkaria reported that there has been a steady increase in reported education-related debt between $150,000 and $200,000, from 12% in 2007 to 16% in 2010. The rate of reported education debt exceeding $200,000 increased more than twofold during the same period, from 8% in 2007 to 17% in 2010. "This may be a pertinent financial barrier or deterrent to potential trainees who are considering careers in cardiothoracic surgery," he commented.

When asked about the adequacy of their residency training, 79%-85% described their current training program as adequate and 39% anticipate additional training, primarily in congenital pediatric surgery or transplant and assisted heart devices.

The survey found that use of the Thoracic Surgery Directors Association (TSDA) curriculum "is sporadic, both on an individual and programmatic level," Dr. Sarkaria said. "When asked about the benefit of the TDSA curriculum as an adjunct to their own educational clinical curriculums, 55% say that it is a useful adjunct, while the rest are uncertain of the benefit. I think this shows an opportunity for expansion upon the innovative foundation of the TSDA curriculum to create an improved, uniform, easily accessible, and relevant central repository of knowledge."

When asked about their primary determinants in deciding on a career in cardiothoracic surgery, types of cases and mentorship were the most important factors cited (41% and 32%, respectively).

When asked about when their choice of cardiothoracic surgery career was made – before, during, or after medical school (in general surgery residency) – no time point stood out. "All of these time points represent opportunities for us to improve our identification and mentorship of potential trainees, and provide the curricular flexibility allowing us to matriculate them into cardiothoracic residencies at these various educational stages," Dr. Sarkaria said.

He acknowledged certain limitations of the study, including its self-reported design. "There can certainly be variable interpretation of the questions by residents," he said. "There can also be situational/circumstantial bias at the time the resident is taking the thoracic in-service exam."

Dr. Sarkaria said that he had no relevant financial disclosures.

SAN DIEGO – Results from the latest workforce survey conducted by the Thoracic Surgery Residents Association reveal some troubling trends.

Nearly one-third of respondents who identified themselves as seeking employment (31%) reported having no job offers 10-12 weeks before completing their residency, and 17% reported education-related debt exceeding $200,000.

"We have to anticipate that continued unease regarding job availability, combined with increasing debt burden, may be a concern for potential trainees, and a possible deterrent or barrier to their matriculation into cardiothoracic surgery," Dr. Inderpal S. Sarkaria said at the annual meeting of the Society of Thoracic Surgeons.

At the same time, however, 65% of survey respondents said that they would positively recommend cardiothoracic surgery as a career to potential applicants. "I believe that the attraction and thrill of what we do as cardiothoracic surgeons is real and will always be an advantage to our specialty in attracting potential trainees," said Dr. Sarkaria, a cardiothoracic surgeon at Memorial Sloan-Kettering Cancer Center, New York.

First administered in 2006, the Thoracic Surgery Residents Association (TSRA) Workforce Survey became mandatory in 2007 as a prerequisite to taking the American Board of Surgery In-Training Examination (ABSITE), which is typically taken during the final 10-12 weeks of cardiothoracic residency. Results from a separate TSRA survey question administered during the 2009 ABSITE identified approximately 11% of general surgery residents anticipating careers in cardiothoracic surgery.

"This is encouraging and has been steady over the past few years, but it’s still far diminished from prior years," Dr. Sarkaria said. "Other surveys from the STS [Society of Thoracic Surgeons] and the American Association of Medical Colleges have identified primary concerns and factors affecting general surgery residents’ choice of specialty, such as job security/availability, ability to balance work and personal life, mentorship, and length of training."

Concerns regarding these decreased matriculation rates, he continued, "are compounded by concerns regarding an anticipated shortage of cardiothoracic surgeons over the next 1-2 decades, in which some have suggested that an additional 100 surgeons per year will need to be trained in order to overcome this."

On behalf of the TSRA executive committee, Dr. Sarkaria presented results from 299 cardiothoracic surgery residents who completed the 2010 survey, which included questions about employment, training experience, education-related debt, and determinants of career choice.

Of the 299 respondents, 228 (76%) were citizens of the United States. The majority (84%) were from 2- or 3-year residency programs, while 9% were from 6-year integrated programs. More than half (69%) were in postgraduate years 6-10.

Nearly one-third of respondents (32%) identified adult cardiac as their primary career of interest, followed by mixed cardiothoracic (23%), general thoracic (22%), congenital (11%), heart failure/lung transplant (5%), aortic (5%), and other (2%).

Among respondents who identified themselves as seeking employment, 45% reported that they had more than two job interviews by the time they completed the survey, 23% had two interviews, 15% had one interview, and 17% had no interviews. In addition, 41% reported that they had two or more firm job offers at the time they completed the survey, 28% had one job offer, and 31% had no job offer.

Dr. Sarkaria reported that there has been a steady increase in reported education-related debt between $150,000 and $200,000, from 12% in 2007 to 16% in 2010. The rate of reported education debt exceeding $200,000 increased more than twofold during the same period, from 8% in 2007 to 17% in 2010. "This may be a pertinent financial barrier or deterrent to potential trainees who are considering careers in cardiothoracic surgery," he commented.

When asked about the adequacy of their residency training, 79%-85% described their current training program as adequate and 39% anticipate additional training, primarily in congenital pediatric surgery or transplant and assisted heart devices.

The survey found that use of the Thoracic Surgery Directors Association (TSDA) curriculum "is sporadic, both on an individual and programmatic level," Dr. Sarkaria said. "When asked about the benefit of the TDSA curriculum as an adjunct to their own educational clinical curriculums, 55% say that it is a useful adjunct, while the rest are uncertain of the benefit. I think this shows an opportunity for expansion upon the innovative foundation of the TSDA curriculum to create an improved, uniform, easily accessible, and relevant central repository of knowledge."

When asked about their primary determinants in deciding on a career in cardiothoracic surgery, types of cases and mentorship were the most important factors cited (41% and 32%, respectively).

When asked about when their choice of cardiothoracic surgery career was made – before, during, or after medical school (in general surgery residency) – no time point stood out. "All of these time points represent opportunities for us to improve our identification and mentorship of potential trainees, and provide the curricular flexibility allowing us to matriculate them into cardiothoracic residencies at these various educational stages," Dr. Sarkaria said.

He acknowledged certain limitations of the study, including its self-reported design. "There can certainly be variable interpretation of the questions by residents," he said. "There can also be situational/circumstantial bias at the time the resident is taking the thoracic in-service exam."

Dr. Sarkaria said that he had no relevant financial disclosures.

SAN DIEGO – Results from the latest workforce survey conducted by the Thoracic Surgery Residents Association reveal some troubling trends.

Nearly one-third of respondents who identified themselves as seeking employment (31%) reported having no job offers 10-12 weeks before completing their residency, and 17% reported education-related debt exceeding $200,000.

"We have to anticipate that continued unease regarding job availability, combined with increasing debt burden, may be a concern for potential trainees, and a possible deterrent or barrier to their matriculation into cardiothoracic surgery," Dr. Inderpal S. Sarkaria said at the annual meeting of the Society of Thoracic Surgeons.

At the same time, however, 65% of survey respondents said that they would positively recommend cardiothoracic surgery as a career to potential applicants. "I believe that the attraction and thrill of what we do as cardiothoracic surgeons is real and will always be an advantage to our specialty in attracting potential trainees," said Dr. Sarkaria, a cardiothoracic surgeon at Memorial Sloan-Kettering Cancer Center, New York.

First administered in 2006, the Thoracic Surgery Residents Association (TSRA) Workforce Survey became mandatory in 2007 as a prerequisite to taking the American Board of Surgery In-Training Examination (ABSITE), which is typically taken during the final 10-12 weeks of cardiothoracic residency. Results from a separate TSRA survey question administered during the 2009 ABSITE identified approximately 11% of general surgery residents anticipating careers in cardiothoracic surgery.

"This is encouraging and has been steady over the past few years, but it’s still far diminished from prior years," Dr. Sarkaria said. "Other surveys from the STS [Society of Thoracic Surgeons] and the American Association of Medical Colleges have identified primary concerns and factors affecting general surgery residents’ choice of specialty, such as job security/availability, ability to balance work and personal life, mentorship, and length of training."

Concerns regarding these decreased matriculation rates, he continued, "are compounded by concerns regarding an anticipated shortage of cardiothoracic surgeons over the next 1-2 decades, in which some have suggested that an additional 100 surgeons per year will need to be trained in order to overcome this."

On behalf of the TSRA executive committee, Dr. Sarkaria presented results from 299 cardiothoracic surgery residents who completed the 2010 survey, which included questions about employment, training experience, education-related debt, and determinants of career choice.

Of the 299 respondents, 228 (76%) were citizens of the United States. The majority (84%) were from 2- or 3-year residency programs, while 9% were from 6-year integrated programs. More than half (69%) were in postgraduate years 6-10.

Nearly one-third of respondents (32%) identified adult cardiac as their primary career of interest, followed by mixed cardiothoracic (23%), general thoracic (22%), congenital (11%), heart failure/lung transplant (5%), aortic (5%), and other (2%).

Among respondents who identified themselves as seeking employment, 45% reported that they had more than two job interviews by the time they completed the survey, 23% had two interviews, 15% had one interview, and 17% had no interviews. In addition, 41% reported that they had two or more firm job offers at the time they completed the survey, 28% had one job offer, and 31% had no job offer.

Dr. Sarkaria reported that there has been a steady increase in reported education-related debt between $150,000 and $200,000, from 12% in 2007 to 16% in 2010. The rate of reported education debt exceeding $200,000 increased more than twofold during the same period, from 8% in 2007 to 17% in 2010. "This may be a pertinent financial barrier or deterrent to potential trainees who are considering careers in cardiothoracic surgery," he commented.

When asked about the adequacy of their residency training, 79%-85% described their current training program as adequate and 39% anticipate additional training, primarily in congenital pediatric surgery or transplant and assisted heart devices.

The survey found that use of the Thoracic Surgery Directors Association (TSDA) curriculum "is sporadic, both on an individual and programmatic level," Dr. Sarkaria said. "When asked about the benefit of the TDSA curriculum as an adjunct to their own educational clinical curriculums, 55% say that it is a useful adjunct, while the rest are uncertain of the benefit. I think this shows an opportunity for expansion upon the innovative foundation of the TSDA curriculum to create an improved, uniform, easily accessible, and relevant central repository of knowledge."

When asked about their primary determinants in deciding on a career in cardiothoracic surgery, types of cases and mentorship were the most important factors cited (41% and 32%, respectively).

When asked about when their choice of cardiothoracic surgery career was made – before, during, or after medical school (in general surgery residency) – no time point stood out. "All of these time points represent opportunities for us to improve our identification and mentorship of potential trainees, and provide the curricular flexibility allowing us to matriculate them into cardiothoracic residencies at these various educational stages," Dr. Sarkaria said.

He acknowledged certain limitations of the study, including its self-reported design. "There can certainly be variable interpretation of the questions by residents," he said. "There can also be situational/circumstantial bias at the time the resident is taking the thoracic in-service exam."

Dr. Sarkaria said that he had no relevant financial disclosures.

SAN DIEGO – Results from the latest workforce survey conducted by the Thoracic Surgery Residents Association reveal some troubling trends.

Nearly one-third of respondents who identified themselves as seeking employment (31%) reported having no job offers 10-12 weeks before completing their residency, and 17% reported education-related debt exceeding $200,000.

"We have to anticipate that continued unease regarding job availability, combined with increasing debt burden, may be a concern for potential trainees, and a possible deterrent or barrier to their matriculation into cardiothoracic surgery," Dr. Inderpal S. Sarkaria said at the annual meeting of the Society of Thoracic Surgeons.

At the same time, however, 65% of survey respondents said that they would positively recommend cardiothoracic surgery as a career to potential applicants. "I believe that the attraction and thrill of what we do as cardiothoracic surgeons is real and will always be an advantage to our specialty in attracting potential trainees," said Dr. Sarkaria, a cardiothoracic surgeon at Memorial Sloan-Kettering Cancer Center, New York.

First administered in 2006, the Thoracic Surgery Residents Association (TSRA) Workforce Survey became mandatory in 2007 as a prerequisite to taking the American Board of Surgery In-Training Examination (ABSITE), which is typically taken during the final 10-12 weeks of cardiothoracic residency. Results from a separate TSRA survey question administered during the 2009 ABSITE identified approximately 11% of general surgery residents anticipating careers in cardiothoracic surgery.

"This is encouraging and has been steady over the past few years, but it’s still far diminished from prior years," Dr. Sarkaria said. "Other surveys from the STS [Society of Thoracic Surgeons] and the American Association of Medical Colleges have identified primary concerns and factors affecting general surgery residents’ choice of specialty, such as job security/availability, ability to balance work and personal life, mentorship, and length of training."

Concerns regarding these decreased matriculation rates, he continued, "are compounded by concerns regarding an anticipated shortage of cardiothoracic surgeons over the next 1-2 decades, in which some have suggested that an additional 100 surgeons per year will need to be trained in order to overcome this."

On behalf of the TSRA executive committee, Dr. Sarkaria presented results from 299 cardiothoracic surgery residents who completed the 2010 survey, which included questions about employment, training experience, education-related debt, and determinants of career choice.

Of the 299 respondents, 228 (76%) were citizens of the United States. The majority (84%) were from 2- or 3-year residency programs, while 9% were from 6-year integrated programs. More than half (69%) were in postgraduate years 6-10.

Nearly one-third of respondents (32%) identified adult cardiac as their primary career of interest, followed by mixed cardiothoracic (23%), general thoracic (22%), congenital (11%), heart failure/lung transplant (5%), aortic (5%), and other (2%).

Among respondents who identified themselves as seeking employment, 45% reported that they had more than two job interviews by the time they completed the survey, 23% had two interviews, 15% had one interview, and 17% had no interviews. In addition, 41% reported that they had two or more firm job offers at the time they completed the survey, 28% had one job offer, and 31% had no job offer.

Dr. Sarkaria reported that there has been a steady increase in reported education-related debt between $150,000 and $200,000, from 12% in 2007 to 16% in 2010. The rate of reported education debt exceeding $200,000 increased more than twofold during the same period, from 8% in 2007 to 17% in 2010. "This may be a pertinent financial barrier or deterrent to potential trainees who are considering careers in cardiothoracic surgery," he commented.

When asked about the adequacy of their residency training, 79%-85% described their current training program as adequate and 39% anticipate additional training, primarily in congenital pediatric surgery or transplant and assisted heart devices.

The survey found that use of the Thoracic Surgery Directors Association (TSDA) curriculum "is sporadic, both on an individual and programmatic level," Dr. Sarkaria said. "When asked about the benefit of the TDSA curriculum as an adjunct to their own educational clinical curriculums, 55% say that it is a useful adjunct, while the rest are uncertain of the benefit. I think this shows an opportunity for expansion upon the innovative foundation of the TSDA curriculum to create an improved, uniform, easily accessible, and relevant central repository of knowledge."

When asked about their primary determinants in deciding on a career in cardiothoracic surgery, types of cases and mentorship were the most important factors cited (41% and 32%, respectively).

When asked about when their choice of cardiothoracic surgery career was made – before, during, or after medical school (in general surgery residency) – no time point stood out. "All of these time points represent opportunities for us to improve our identification and mentorship of potential trainees, and provide the curricular flexibility allowing us to matriculate them into cardiothoracic residencies at these various educational stages," Dr. Sarkaria said.

He acknowledged certain limitations of the study, including its self-reported design. "There can certainly be variable interpretation of the questions by residents," he said. "There can also be situational/circumstantial bias at the time the resident is taking the thoracic in-service exam."

Dr. Sarkaria said that he had no relevant financial disclosures.

SAN DIEGO – Results from the latest workforce survey conducted by the Thoracic Surgery Residents Association reveal some troubling trends.

Nearly one-third of respondents who identified themselves as seeking employment (31%) reported having no job offers 10-12 weeks before completing their residency, and 17% reported education-related debt exceeding $200,000.

"We have to anticipate that continued unease regarding job availability, combined with increasing debt burden, may be a concern for potential trainees, and a possible deterrent or barrier to their matriculation into cardiothoracic surgery," Dr. Inderpal S. Sarkaria said at the annual meeting of the Society of Thoracic Surgeons.

At the same time, however, 65% of survey respondents said that they would positively recommend cardiothoracic surgery as a career to potential applicants. "I believe that the attraction and thrill of what we do as cardiothoracic surgeons is real and will always be an advantage to our specialty in attracting potential trainees," said Dr. Sarkaria, a cardiothoracic surgeon at Memorial Sloan-Kettering Cancer Center, New York.

First administered in 2006, the Thoracic Surgery Residents Association (TSRA) Workforce Survey became mandatory in 2007 as a prerequisite to taking the American Board of Surgery In-Training Examination (ABSITE), which is typically taken during the final 10-12 weeks of cardiothoracic residency. Results from a separate TSRA survey question administered during the 2009 ABSITE identified approximately 11% of general surgery residents anticipating careers in cardiothoracic surgery.

"This is encouraging and has been steady over the past few years, but it’s still far diminished from prior years," Dr. Sarkaria said. "Other surveys from the STS [Society of Thoracic Surgeons] and the American Association of Medical Colleges have identified primary concerns and factors affecting general surgery residents’ choice of specialty, such as job security/availability, ability to balance work and personal life, mentorship, and length of training."

Concerns regarding these decreased matriculation rates, he continued, "are compounded by concerns regarding an anticipated shortage of cardiothoracic surgeons over the next 1-2 decades, in which some have suggested that an additional 100 surgeons per year will need to be trained in order to overcome this."

On behalf of the TSRA executive committee, Dr. Sarkaria presented results from 299 cardiothoracic surgery residents who completed the 2010 survey, which included questions about employment, training experience, education-related debt, and determinants of career choice.

Of the 299 respondents, 228 (76%) were citizens of the United States. The majority (84%) were from 2- or 3-year residency programs, while 9% were from 6-year integrated programs. More than half (69%) were in postgraduate years 6-10.

Nearly one-third of respondents (32%) identified adult cardiac as their primary career of interest, followed by mixed cardiothoracic (23%), general thoracic (22%), congenital (11%), heart failure/lung transplant (5%), aortic (5%), and other (2%).

Among respondents who identified themselves as seeking employment, 45% reported that they had more than two job interviews by the time they completed the survey, 23% had two interviews, 15% had one interview, and 17% had no interviews. In addition, 41% reported that they had two or more firm job offers at the time they completed the survey, 28% had one job offer, and 31% had no job offer.

Dr. Sarkaria reported that there has been a steady increase in reported education-related debt between $150,000 and $200,000, from 12% in 2007 to 16% in 2010. The rate of reported education debt exceeding $200,000 increased more than twofold during the same period, from 8% in 2007 to 17% in 2010. "This may be a pertinent financial barrier or deterrent to potential trainees who are considering careers in cardiothoracic surgery," he commented.

When asked about the adequacy of their residency training, 79%-85% described their current training program as adequate and 39% anticipate additional training, primarily in congenital pediatric surgery or transplant and assisted heart devices.

The survey found that use of the Thoracic Surgery Directors Association (TSDA) curriculum "is sporadic, both on an individual and programmatic level," Dr. Sarkaria said. "When asked about the benefit of the TDSA curriculum as an adjunct to their own educational clinical curriculums, 55% say that it is a useful adjunct, while the rest are uncertain of the benefit. I think this shows an opportunity for expansion upon the innovative foundation of the TSDA curriculum to create an improved, uniform, easily accessible, and relevant central repository of knowledge."

When asked about their primary determinants in deciding on a career in cardiothoracic surgery, types of cases and mentorship were the most important factors cited (41% and 32%, respectively).

When asked about when their choice of cardiothoracic surgery career was made – before, during, or after medical school (in general surgery residency) – no time point stood out. "All of these time points represent opportunities for us to improve our identification and mentorship of potential trainees, and provide the curricular flexibility allowing us to matriculate them into cardiothoracic residencies at these various educational stages," Dr. Sarkaria said.

He acknowledged certain limitations of the study, including its self-reported design. "There can certainly be variable interpretation of the questions by residents," he said. "There can also be situational/circumstantial bias at the time the resident is taking the thoracic in-service exam."

Dr. Sarkaria said that he had no relevant financial disclosures.

SAN DIEGO – Antimicrobial resistance continues to be a significant problem, but a few new agents have shown promise against certain pathogens.

"As clinicians, we need to look forward to new drug discovery and development, and keep an eye on the current pipeline," April D. Miller, Pharm. D., said at the annual congress of the Society of Critical Care Medicine. "We also need to think of and study new and unique strategies to preserve the agents that we currently have available."

The problem of antimicrobial resistance "lies in the bugs themselves," said Dr. Miller of the South Carolina College of Pharmacy at the University of South Carolina, Columbia. Among gram-positive organisms, she said, there are rising rates of community- and hospital-acquired methicillin-resistant Staphylococcus aureus and rising minimum inhibitory concentrations to vancomycin. There are also increasing rates of vancomycin-resistant Enterococci, and reports about the possibility of linezolid-resistant Enterococci. In addition, she said, "increases in the rate of Streptococcus pneumoniae resistance can impact ICU clinicians as patients come in from the community with resistant organisms because of inadequately treated infections."

This prompted the Infectious Diseases Society of America to launch an initiative in 2010 calling for the development of 10 new antibiotics by the year 2020. One of those new agents is telavancin, a lipoglycopeptide from Theravance that was approved in September 2009 for complicated skin and skin-structure infections and is currently marketed under the brand name Vibativ. Two other lipoglycopeptides, dalbavancin and oritavancin, are not currently available and continue to be studied.

Newer lipoglycopeptides influence cell membrane potential in addition to inhibiting cell wall synthesis by preventing polymerization and cross-linking of the cell wall, Dr. Miller said. They also feature increased protein binding. "While there are not a lot of data on what this means clinically, they do have the ability to affect their penetration into various body sites," she explained. "These new mechanisms and new binding sites afford us additional and expanded spectrums of activity."

Lipoglycopeptides also have unique pharmacokinetics compared with currently available agents. For example, the half-life of vancomycin is 6-12 hours, while that of telavancin is 7.5 hours. Both oritavancin and dalbavancin have a half-life of about 195 hours. "In clinical studies, the manufacturers are exploring once-weekly or twice-weekly dosing [of oritavancin and dalbavancin], which would be of tremendous benefit for outpatients," Dr. Miller commented. "But for ICU patients we think about the possibility of adverse reactions or dosing issues as renal function changes. That could be a real problem because of the prolonged elimination."

The phase III trial of telavancin for complicated skin and skin-structure infections found that a dose of 10 mg/kg IV daily was as effective as vancomycin 1 g IV every 12 hours (Clin. Infect. Dis. 2008;46:1683-93).

Two phase II trials of telavancin for hospital-acquired pneumonia found that a dose of 10 mg/kg IV daily was not inferior to vancomycin 1,000 mg daily. The unpublished studies involved 1,503 patients and "were good enough for FDA approval, but leave us with some lingering questions about how telavancin compares to vancomycin for hospital-acquired pneumonia," Dr. Miller said.

Among all three telavancin studies combined, a higher proportion of patients in the telavancin group experienced a 1.5-fold increase of serum creatinine from baseline, compared with their counterparts in the vancomycin group (15% vs. 7%, respectively). The proportion of adverse renal events was also higher in the telavancin group (3.1% vs. 1.1%).

Dr. Miller next discussed ceftaroline, a fourth-generation cephalosporin approved in October 2010 for acute skin and skin-structure infections as well as for community-acquired bacterial pneumonia. The drug is expected to be on the market soon under the brand name Teflaro (Forest Laboratories).

"Its spectrum of activity is quite different from that of the other cephalosporins, such that it retains activity against methicillin-susceptible Staphylococcus aureus isolates as well as isolates that are resistant to vancomycin," Dr. Miller said. "It has very good activity against Streptococcus pneumoniae, and like other cephalosporins it has minimal activity against Enterococci. It retains activity against Moraxella catarrhalis and Haemophilus influenzae, which we think about as common pathogens in community-acquired pneumonia. It has some activity against Klebsiella species, but unfortunately it doesn’t have any activity against extended-spectrum beta-lactamase producers or Pseudomonas species. So when we think about empiric coverage, there are definitely some holes with ceftaroline."

The recommended dosing of ceftaroline is 600 mg IV every 12 hours. The half-life is 1.6 hours for single doses and 2.66 hours for multiple doses.

Two phase III studies comparing ceftaroline with ceftriaxone in the treatment of community-acquired pneumonia were presented during the 2009 meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy. The studies demonstrated higher cure rates for patients in the ceftaroline group, compared with those in the ceftriaxone group (83% vs. 77%, respectively, among all study participants, and 86% vs. 69% among patients with S. pneumoniae).

Another strategy for combating antibiotic resistance involves improving ways to use available antibiotics on the market. Dr. Miller said that there are eight National Institutes of Health–funded trials aimed at this approach, including short-course therapy, narrow-spectrum therapies, combination vs. monotherapy, and pharmacodynamic dosing guidance.

Dr. Miller said that she had no relevant financial disclosures to make.

SAN DIEGO – Antimicrobial resistance continues to be a significant problem, but a few new agents have shown promise against certain pathogens.

"As clinicians, we need to look forward to new drug discovery and development, and keep an eye on the current pipeline," April D. Miller, Pharm. D., said at the annual congress of the Society of Critical Care Medicine. "We also need to think of and study new and unique strategies to preserve the agents that we currently have available."

The problem of antimicrobial resistance "lies in the bugs themselves," said Dr. Miller of the South Carolina College of Pharmacy at the University of South Carolina, Columbia. Among gram-positive organisms, she said, there are rising rates of community- and hospital-acquired methicillin-resistant Staphylococcus aureus and rising minimum inhibitory concentrations to vancomycin. There are also increasing rates of vancomycin-resistant Enterococci, and reports about the possibility of linezolid-resistant Enterococci. In addition, she said, "increases in the rate of Streptococcus pneumoniae resistance can impact ICU clinicians as patients come in from the community with resistant organisms because of inadequately treated infections."

This prompted the Infectious Diseases Society of America to launch an initiative in 2010 calling for the development of 10 new antibiotics by the year 2020. One of those new agents is telavancin, a lipoglycopeptide from Theravance that was approved in September 2009 for complicated skin and skin-structure infections and is currently marketed under the brand name Vibativ. Two other lipoglycopeptides, dalbavancin and oritavancin, are not currently available and continue to be studied.

Newer lipoglycopeptides influence cell membrane potential in addition to inhibiting cell wall synthesis by preventing polymerization and cross-linking of the cell wall, Dr. Miller said. They also feature increased protein binding. "While there are not a lot of data on what this means clinically, they do have the ability to affect their penetration into various body sites," she explained. "These new mechanisms and new binding sites afford us additional and expanded spectrums of activity."

Lipoglycopeptides also have unique pharmacokinetics compared with currently available agents. For example, the half-life of vancomycin is 6-12 hours, while that of telavancin is 7.5 hours. Both oritavancin and dalbavancin have a half-life of about 195 hours. "In clinical studies, the manufacturers are exploring once-weekly or twice-weekly dosing [of oritavancin and dalbavancin], which would be of tremendous benefit for outpatients," Dr. Miller commented. "But for ICU patients we think about the possibility of adverse reactions or dosing issues as renal function changes. That could be a real problem because of the prolonged elimination."

The phase III trial of telavancin for complicated skin and skin-structure infections found that a dose of 10 mg/kg IV daily was as effective as vancomycin 1 g IV every 12 hours (Clin. Infect. Dis. 2008;46:1683-93).

Two phase II trials of telavancin for hospital-acquired pneumonia found that a dose of 10 mg/kg IV daily was not inferior to vancomycin 1,000 mg daily. The unpublished studies involved 1,503 patients and "were good enough for FDA approval, but leave us with some lingering questions about how telavancin compares to vancomycin for hospital-acquired pneumonia," Dr. Miller said.

Among all three telavancin studies combined, a higher proportion of patients in the telavancin group experienced a 1.5-fold increase of serum creatinine from baseline, compared with their counterparts in the vancomycin group (15% vs. 7%, respectively). The proportion of adverse renal events was also higher in the telavancin group (3.1% vs. 1.1%).

Dr. Miller next discussed ceftaroline, a fourth-generation cephalosporin approved in October 2010 for acute skin and skin-structure infections as well as for community-acquired bacterial pneumonia. The drug is expected to be on the market soon under the brand name Teflaro (Forest Laboratories).

"Its spectrum of activity is quite different from that of the other cephalosporins, such that it retains activity against methicillin-susceptible Staphylococcus aureus isolates as well as isolates that are resistant to vancomycin," Dr. Miller said. "It has very good activity against Streptococcus pneumoniae, and like other cephalosporins it has minimal activity against Enterococci. It retains activity against Moraxella catarrhalis and Haemophilus influenzae, which we think about as common pathogens in community-acquired pneumonia. It has some activity against Klebsiella species, but unfortunately it doesn’t have any activity against extended-spectrum beta-lactamase producers or Pseudomonas species. So when we think about empiric coverage, there are definitely some holes with ceftaroline."

The recommended dosing of ceftaroline is 600 mg IV every 12 hours. The half-life is 1.6 hours for single doses and 2.66 hours for multiple doses.

Two phase III studies comparing ceftaroline with ceftriaxone in the treatment of community-acquired pneumonia were presented during the 2009 meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy. The studies demonstrated higher cure rates for patients in the ceftaroline group, compared with those in the ceftriaxone group (83% vs. 77%, respectively, among all study participants, and 86% vs. 69% among patients with S. pneumoniae).

Another strategy for combating antibiotic resistance involves improving ways to use available antibiotics on the market. Dr. Miller said that there are eight National Institutes of Health–funded trials aimed at this approach, including short-course therapy, narrow-spectrum therapies, combination vs. monotherapy, and pharmacodynamic dosing guidance.

Dr. Miller said that she had no relevant financial disclosures to make.

SAN DIEGO – Antimicrobial resistance continues to be a significant problem, but a few new agents have shown promise against certain pathogens.

"As clinicians, we need to look forward to new drug discovery and development, and keep an eye on the current pipeline," April D. Miller, Pharm. D., said at the annual congress of the Society of Critical Care Medicine. "We also need to think of and study new and unique strategies to preserve the agents that we currently have available."

The problem of antimicrobial resistance "lies in the bugs themselves," said Dr. Miller of the South Carolina College of Pharmacy at the University of South Carolina, Columbia. Among gram-positive organisms, she said, there are rising rates of community- and hospital-acquired methicillin-resistant Staphylococcus aureus and rising minimum inhibitory concentrations to vancomycin. There are also increasing rates of vancomycin-resistant Enterococci, and reports about the possibility of linezolid-resistant Enterococci. In addition, she said, "increases in the rate of Streptococcus pneumoniae resistance can impact ICU clinicians as patients come in from the community with resistant organisms because of inadequately treated infections."

This prompted the Infectious Diseases Society of America to launch an initiative in 2010 calling for the development of 10 new antibiotics by the year 2020. One of those new agents is telavancin, a lipoglycopeptide from Theravance that was approved in September 2009 for complicated skin and skin-structure infections and is currently marketed under the brand name Vibativ. Two other lipoglycopeptides, dalbavancin and oritavancin, are not currently available and continue to be studied.

Newer lipoglycopeptides influence cell membrane potential in addition to inhibiting cell wall synthesis by preventing polymerization and cross-linking of the cell wall, Dr. Miller said. They also feature increased protein binding. "While there are not a lot of data on what this means clinically, they do have the ability to affect their penetration into various body sites," she explained. "These new mechanisms and new binding sites afford us additional and expanded spectrums of activity."

Lipoglycopeptides also have unique pharmacokinetics compared with currently available agents. For example, the half-life of vancomycin is 6-12 hours, while that of telavancin is 7.5 hours. Both oritavancin and dalbavancin have a half-life of about 195 hours. "In clinical studies, the manufacturers are exploring once-weekly or twice-weekly dosing [of oritavancin and dalbavancin], which would be of tremendous benefit for outpatients," Dr. Miller commented. "But for ICU patients we think about the possibility of adverse reactions or dosing issues as renal function changes. That could be a real problem because of the prolonged elimination."

The phase III trial of telavancin for complicated skin and skin-structure infections found that a dose of 10 mg/kg IV daily was as effective as vancomycin 1 g IV every 12 hours (Clin. Infect. Dis. 2008;46:1683-93).

Two phase II trials of telavancin for hospital-acquired pneumonia found that a dose of 10 mg/kg IV daily was not inferior to vancomycin 1,000 mg daily. The unpublished studies involved 1,503 patients and "were good enough for FDA approval, but leave us with some lingering questions about how telavancin compares to vancomycin for hospital-acquired pneumonia," Dr. Miller said.

Among all three telavancin studies combined, a higher proportion of patients in the telavancin group experienced a 1.5-fold increase of serum creatinine from baseline, compared with their counterparts in the vancomycin group (15% vs. 7%, respectively). The proportion of adverse renal events was also higher in the telavancin group (3.1% vs. 1.1%).

Dr. Miller next discussed ceftaroline, a fourth-generation cephalosporin approved in October 2010 for acute skin and skin-structure infections as well as for community-acquired bacterial pneumonia. The drug is expected to be on the market soon under the brand name Teflaro (Forest Laboratories).

"Its spectrum of activity is quite different from that of the other cephalosporins, such that it retains activity against methicillin-susceptible Staphylococcus aureus isolates as well as isolates that are resistant to vancomycin," Dr. Miller said. "It has very good activity against Streptococcus pneumoniae, and like other cephalosporins it has minimal activity against Enterococci. It retains activity against Moraxella catarrhalis and Haemophilus influenzae, which we think about as common pathogens in community-acquired pneumonia. It has some activity against Klebsiella species, but unfortunately it doesn’t have any activity against extended-spectrum beta-lactamase producers or Pseudomonas species. So when we think about empiric coverage, there are definitely some holes with ceftaroline."

The recommended dosing of ceftaroline is 600 mg IV every 12 hours. The half-life is 1.6 hours for single doses and 2.66 hours for multiple doses.

Two phase III studies comparing ceftaroline with ceftriaxone in the treatment of community-acquired pneumonia were presented during the 2009 meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy. The studies demonstrated higher cure rates for patients in the ceftaroline group, compared with those in the ceftriaxone group (83% vs. 77%, respectively, among all study participants, and 86% vs. 69% among patients with S. pneumoniae).

Another strategy for combating antibiotic resistance involves improving ways to use available antibiotics on the market. Dr. Miller said that there are eight National Institutes of Health–funded trials aimed at this approach, including short-course therapy, narrow-spectrum therapies, combination vs. monotherapy, and pharmacodynamic dosing guidance.

Dr. Miller said that she had no relevant financial disclosures to make.

SAN DIEGO – An interval between neoadjuvant chemoradiation and esophagectomy that extends beyond 8 weeks is not associated with increased perioperative complications, increased pathological complete response, or change in overall survival, results from a long-term single-center study showed.

"For patients who have not yet recovered from neoadjuvant chemoradiation, it is safe to delay surgery to allow them to improve their performance status," Dr. Jae Y. Kim said at the annual meeting of the Society of Thoracic Surgeons.

Traditionally, he said, surgery has been recommended within 8 weeks after completing neoadjuvant chemoradiation for esophageal cancer, yet many patients choose to delay their surgery.

Some patients have not yet recovered from chemoradiation, while others are delayed for personal or logistical reasons, explained Dr. Kim, a thoracic surgery fellow at the University of Texas M.D. Anderson Cancer Center, Houston. "The impact of this delay on outcomes is unknown." Radiation-induced tumor necrosis increases over time, he said, and there is evidence from rectal cancer that a longer interval may increase the rate of pathological complete response. "On the other hand, there are theoretical concerns that this delay may lead to increased radiation fibrosis and cause a more difficult operation. It is also possible that a delay would allow for tumor regrowth."

In an effort to determine whether an increased interval between chemoradiation and surgery is associated with risk of major perioperative complications or overall survival, Dr. Kim and his associates conducted a retrospective study of 266 patients with esophageal cancer followed by neoadjuvant chemoradiation who were treated at M.D. Anderson in 2002-2008. They divided the patients into two groups: a "short-interval" group of 150 who underwent esophagectomy within 8 weeks of chemoradiation, and a "delayed" group of 116 who underwent esophagectomy more than 8 weeks following chemoradiation.

"Most patients were clustered around 4-11 weeks," Dr. Kim said. "No patient had surgery more than 46 weeks after completing neoadjuvant chemoradiation."

The median interval from completion of neoadjuvant therapy to surgery was 46 days in the short-interval group and 76 days in the delayed group. In both groups, more than 95% of patients were staged with PET-CT and endoscopic ultrasound.

The researchers compared the two groups in terms of perioperative complications, rate of pathological complete response, and overall survival.

The two groups were similar in 18 of 22 baseline characteristics examined, but they were different in four areas. Compared with their counterparts in the short-interval group, the patients in the delayed group were slightly older (mean age, 60 years vs. 57 years, respectively), had more coronary artery disease (17% vs. 7%), had less adenocarcinoma histology (87% vs. 97%), and weighed less (53% with a body mass index of 25 kg/m2 or greater vs. 75% of their counterparts in the short-interval group).

By any objective measure used to gauge the difficulty of the operation, the two groups were similar, including mean OR time (390 minutes in the short-interval group vs. 398 minutes in the delayed group), mean number of lymph nodes removed (21% vs. 20%), and mean estimated blood loss (505 mL vs. 478 mL).

The rates of major complications also were similar between the two groups, including perioperative mortality (2% in the short-interval group vs. 3% in the delayed group), median length of stay (11 days in each group), and rate of anastomotic leak (11% vs. 16%).

The rate of pathological complete response was similar between the two groups (21% vs. 23%).

Overall 5-year survival in the short-interval group was 46%, compared with 36% in the delayed-surgery group, a nonsignificant difference. Disease-free 5-year survival in the short-interval group was 44%, compared with 36% in the delayed group.

"The timing of surgery, both as a continuous and a dichotomous variable, was not associated" with perioperative complication or death, pathological complete response, or overall survival, Dr. Kim added.

On multivariable analysis, older age, more involved lymph nodes, and advanced pathological stage were independently associated with decreased survival.

The researchers performed a subgroup analysis of patients with adenocarcinoma histology and found that the results were similar.

Dr. Kim said that he had no relevant financial disclosures.

SAN DIEGO – An interval between neoadjuvant chemoradiation and esophagectomy that extends beyond 8 weeks is not associated with increased perioperative complications, increased pathological complete response, or change in overall survival, results from a long-term single-center study showed.

"For patients who have not yet recovered from neoadjuvant chemoradiation, it is safe to delay surgery to allow them to improve their performance status," Dr. Jae Y. Kim said at the annual meeting of the Society of Thoracic Surgeons.

Traditionally, he said, surgery has been recommended within 8 weeks after completing neoadjuvant chemoradiation for esophageal cancer, yet many patients choose to delay their surgery.

Some patients have not yet recovered from chemoradiation, while others are delayed for personal or logistical reasons, explained Dr. Kim, a thoracic surgery fellow at the University of Texas M.D. Anderson Cancer Center, Houston. "The impact of this delay on outcomes is unknown." Radiation-induced tumor necrosis increases over time, he said, and there is evidence from rectal cancer that a longer interval may increase the rate of pathological complete response. "On the other hand, there are theoretical concerns that this delay may lead to increased radiation fibrosis and cause a more difficult operation. It is also possible that a delay would allow for tumor regrowth."

In an effort to determine whether an increased interval between chemoradiation and surgery is associated with risk of major perioperative complications or overall survival, Dr. Kim and his associates conducted a retrospective study of 266 patients with esophageal cancer followed by neoadjuvant chemoradiation who were treated at M.D. Anderson in 2002-2008. They divided the patients into two groups: a "short-interval" group of 150 who underwent esophagectomy within 8 weeks of chemoradiation, and a "delayed" group of 116 who underwent esophagectomy more than 8 weeks following chemoradiation.

"Most patients were clustered around 4-11 weeks," Dr. Kim said. "No patient had surgery more than 46 weeks after completing neoadjuvant chemoradiation."

The median interval from completion of neoadjuvant therapy to surgery was 46 days in the short-interval group and 76 days in the delayed group. In both groups, more than 95% of patients were staged with PET-CT and endoscopic ultrasound.

The researchers compared the two groups in terms of perioperative complications, rate of pathological complete response, and overall survival.

The two groups were similar in 18 of 22 baseline characteristics examined, but they were different in four areas. Compared with their counterparts in the short-interval group, the patients in the delayed group were slightly older (mean age, 60 years vs. 57 years, respectively), had more coronary artery disease (17% vs. 7%), had less adenocarcinoma histology (87% vs. 97%), and weighed less (53% with a body mass index of 25 kg/m2 or greater vs. 75% of their counterparts in the short-interval group).

By any objective measure used to gauge the difficulty of the operation, the two groups were similar, including mean OR time (390 minutes in the short-interval group vs. 398 minutes in the delayed group), mean number of lymph nodes removed (21% vs. 20%), and mean estimated blood loss (505 mL vs. 478 mL).

The rates of major complications also were similar between the two groups, including perioperative mortality (2% in the short-interval group vs. 3% in the delayed group), median length of stay (11 days in each group), and rate of anastomotic leak (11% vs. 16%).

The rate of pathological complete response was similar between the two groups (21% vs. 23%).

Overall 5-year survival in the short-interval group was 46%, compared with 36% in the delayed-surgery group, a nonsignificant difference. Disease-free 5-year survival in the short-interval group was 44%, compared with 36% in the delayed group.

"The timing of surgery, both as a continuous and a dichotomous variable, was not associated" with perioperative complication or death, pathological complete response, or overall survival, Dr. Kim added.

On multivariable analysis, older age, more involved lymph nodes, and advanced pathological stage were independently associated with decreased survival.

The researchers performed a subgroup analysis of patients with adenocarcinoma histology and found that the results were similar.

Dr. Kim said that he had no relevant financial disclosures.

SAN DIEGO – An interval between neoadjuvant chemoradiation and esophagectomy that extends beyond 8 weeks is not associated with increased perioperative complications, increased pathological complete response, or change in overall survival, results from a long-term single-center study showed.

"For patients who have not yet recovered from neoadjuvant chemoradiation, it is safe to delay surgery to allow them to improve their performance status," Dr. Jae Y. Kim said at the annual meeting of the Society of Thoracic Surgeons.

Traditionally, he said, surgery has been recommended within 8 weeks after completing neoadjuvant chemoradiation for esophageal cancer, yet many patients choose to delay their surgery.

Some patients have not yet recovered from chemoradiation, while others are delayed for personal or logistical reasons, explained Dr. Kim, a thoracic surgery fellow at the University of Texas M.D. Anderson Cancer Center, Houston. "The impact of this delay on outcomes is unknown." Radiation-induced tumor necrosis increases over time, he said, and there is evidence from rectal cancer that a longer interval may increase the rate of pathological complete response. "On the other hand, there are theoretical concerns that this delay may lead to increased radiation fibrosis and cause a more difficult operation. It is also possible that a delay would allow for tumor regrowth."

In an effort to determine whether an increased interval between chemoradiation and surgery is associated with risk of major perioperative complications or overall survival, Dr. Kim and his associates conducted a retrospective study of 266 patients with esophageal cancer followed by neoadjuvant chemoradiation who were treated at M.D. Anderson in 2002-2008. They divided the patients into two groups: a "short-interval" group of 150 who underwent esophagectomy within 8 weeks of chemoradiation, and a "delayed" group of 116 who underwent esophagectomy more than 8 weeks following chemoradiation.

"Most patients were clustered around 4-11 weeks," Dr. Kim said. "No patient had surgery more than 46 weeks after completing neoadjuvant chemoradiation."

The median interval from completion of neoadjuvant therapy to surgery was 46 days in the short-interval group and 76 days in the delayed group. In both groups, more than 95% of patients were staged with PET-CT and endoscopic ultrasound.

The researchers compared the two groups in terms of perioperative complications, rate of pathological complete response, and overall survival.

The two groups were similar in 18 of 22 baseline characteristics examined, but they were different in four areas. Compared with their counterparts in the short-interval group, the patients in the delayed group were slightly older (mean age, 60 years vs. 57 years, respectively), had more coronary artery disease (17% vs. 7%), had less adenocarcinoma histology (87% vs. 97%), and weighed less (53% with a body mass index of 25 kg/m2 or greater vs. 75% of their counterparts in the short-interval group).

By any objective measure used to gauge the difficulty of the operation, the two groups were similar, including mean OR time (390 minutes in the short-interval group vs. 398 minutes in the delayed group), mean number of lymph nodes removed (21% vs. 20%), and mean estimated blood loss (505 mL vs. 478 mL).

The rates of major complications also were similar between the two groups, including perioperative mortality (2% in the short-interval group vs. 3% in the delayed group), median length of stay (11 days in each group), and rate of anastomotic leak (11% vs. 16%).

The rate of pathological complete response was similar between the two groups (21% vs. 23%).

Overall 5-year survival in the short-interval group was 46%, compared with 36% in the delayed-surgery group, a nonsignificant difference. Disease-free 5-year survival in the short-interval group was 44%, compared with 36% in the delayed group.

"The timing of surgery, both as a continuous and a dichotomous variable, was not associated" with perioperative complication or death, pathological complete response, or overall survival, Dr. Kim added.

On multivariable analysis, older age, more involved lymph nodes, and advanced pathological stage were independently associated with decreased survival.

The researchers performed a subgroup analysis of patients with adenocarcinoma histology and found that the results were similar.

Dr. Kim said that he had no relevant financial disclosures.

SAN DIEGO – An interval between neoadjuvant chemoradiation and esophagectomy that extends beyond 8 weeks is not associated with increased perioperative complications, increased pathological complete response, or change in overall survival, results from a long-term single-center study showed.

"For patients who have not yet recovered from neoadjuvant chemoradiation, it is safe to delay surgery to allow them to improve their performance status," Dr. Jae Y. Kim said at the annual meeting of the Society of Thoracic Surgeons.

Traditionally, he said, surgery has been recommended within 8 weeks after completing neoadjuvant chemoradiation for esophageal cancer, yet many patients choose to delay their surgery.

Some patients have not yet recovered from chemoradiation, while others are delayed for personal or logistical reasons, explained Dr. Kim, a thoracic surgery fellow at the University of Texas M.D. Anderson Cancer Center, Houston. "The impact of this delay on outcomes is unknown." Radiation-induced tumor necrosis increases over time, he said, and there is evidence from rectal cancer that a longer interval may increase the rate of pathological complete response. "On the other hand, there are theoretical concerns that this delay may lead to increased radiation fibrosis and cause a more difficult operation. It is also possible that a delay would allow for tumor regrowth."

In an effort to determine whether an increased interval between chemoradiation and surgery is associated with risk of major perioperative complications or overall survival, Dr. Kim and his associates conducted a retrospective study of 266 patients with esophageal cancer followed by neoadjuvant chemoradiation who were treated at M.D. Anderson in 2002-2008. They divided the patients into two groups: a "short-interval" group of 150 who underwent esophagectomy within 8 weeks of chemoradiation, and a "delayed" group of 116 who underwent esophagectomy more than 8 weeks following chemoradiation.

"Most patients were clustered around 4-11 weeks," Dr. Kim said. "No patient had surgery more than 46 weeks after completing neoadjuvant chemoradiation."

The median interval from completion of neoadjuvant therapy to surgery was 46 days in the short-interval group and 76 days in the delayed group. In both groups, more than 95% of patients were staged with PET-CT and endoscopic ultrasound.

The researchers compared the two groups in terms of perioperative complications, rate of pathological complete response, and overall survival.

The two groups were similar in 18 of 22 baseline characteristics examined, but they were different in four areas. Compared with their counterparts in the short-interval group, the patients in the delayed group were slightly older (mean age, 60 years vs. 57 years, respectively), had more coronary artery disease (17% vs. 7%), had less adenocarcinoma histology (87% vs. 97%), and weighed less (53% with a body mass index of 25 kg/m2 or greater vs. 75% of their counterparts in the short-interval group).

By any objective measure used to gauge the difficulty of the operation, the two groups were similar, including mean OR time (390 minutes in the short-interval group vs. 398 minutes in the delayed group), mean number of lymph nodes removed (21% vs. 20%), and mean estimated blood loss (505 mL vs. 478 mL).

The rates of major complications also were similar between the two groups, including perioperative mortality (2% in the short-interval group vs. 3% in the delayed group), median length of stay (11 days in each group), and rate of anastomotic leak (11% vs. 16%).

The rate of pathological complete response was similar between the two groups (21% vs. 23%).

Overall 5-year survival in the short-interval group was 46%, compared with 36% in the delayed-surgery group, a nonsignificant difference. Disease-free 5-year survival in the short-interval group was 44%, compared with 36% in the delayed group.

"The timing of surgery, both as a continuous and a dichotomous variable, was not associated" with perioperative complication or death, pathological complete response, or overall survival, Dr. Kim added.

On multivariable analysis, older age, more involved lymph nodes, and advanced pathological stage were independently associated with decreased survival.

The researchers performed a subgroup analysis of patients with adenocarcinoma histology and found that the results were similar.

Dr. Kim said that he had no relevant financial disclosures.

SAN DIEGO – An interval between neoadjuvant chemoradiation and esophagectomy that extends beyond 8 weeks is not associated with increased perioperative complications, increased pathological complete response, or change in overall survival, results from a long-term single-center study showed.

"For patients who have not yet recovered from neoadjuvant chemoradiation, it is safe to delay surgery to allow them to improve their performance status," Dr. Jae Y. Kim said at the annual meeting of the Society of Thoracic Surgeons.

Traditionally, he said, surgery has been recommended within 8 weeks after completing neoadjuvant chemoradiation for esophageal cancer, yet many patients choose to delay their surgery.

Some patients have not yet recovered from chemoradiation, while others are delayed for personal or logistical reasons, explained Dr. Kim, a thoracic surgery fellow at the University of Texas M.D. Anderson Cancer Center, Houston. "The impact of this delay on outcomes is unknown." Radiation-induced tumor necrosis increases over time, he said, and there is evidence from rectal cancer that a longer interval may increase the rate of pathological complete response. "On the other hand, there are theoretical concerns that this delay may lead to increased radiation fibrosis and cause a more difficult operation. It is also possible that a delay would allow for tumor regrowth."

In an effort to determine whether an increased interval between chemoradiation and surgery is associated with risk of major perioperative complications or overall survival, Dr. Kim and his associates conducted a retrospective study of 266 patients with esophageal cancer followed by neoadjuvant chemoradiation who were treated at M.D. Anderson in 2002-2008. They divided the patients into two groups: a "short-interval" group of 150 who underwent esophagectomy within 8 weeks of chemoradiation, and a "delayed" group of 116 who underwent esophagectomy more than 8 weeks following chemoradiation.

"Most patients were clustered around 4-11 weeks," Dr. Kim said. "No patient had surgery more than 46 weeks after completing neoadjuvant chemoradiation."

The median interval from completion of neoadjuvant therapy to surgery was 46 days in the short-interval group and 76 days in the delayed group. In both groups, more than 95% of patients were staged with PET-CT and endoscopic ultrasound.

The researchers compared the two groups in terms of perioperative complications, rate of pathological complete response, and overall survival.

The two groups were similar in 18 of 22 baseline characteristics examined, but they were different in four areas. Compared with their counterparts in the short-interval group, the patients in the delayed group were slightly older (mean age, 60 years vs. 57 years, respectively), had more coronary artery disease (17% vs. 7%), had less adenocarcinoma histology (87% vs. 97%), and weighed less (53% with a body mass index of 25 kg/m2 or greater vs. 75% of their counterparts in the short-interval group).

By any objective measure used to gauge the difficulty of the operation, the two groups were similar, including mean OR time (390 minutes in the short-interval group vs. 398 minutes in the delayed group), mean number of lymph nodes removed (21% vs. 20%), and mean estimated blood loss (505 mL vs. 478 mL).

The rates of major complications also were similar between the two groups, including perioperative mortality (2% in the short-interval group vs. 3% in the delayed group), median length of stay (11 days in each group), and rate of anastomotic leak (11% vs. 16%).

The rate of pathological complete response was similar between the two groups (21% vs. 23%).

Overall 5-year survival in the short-interval group was 46%, compared with 36% in the delayed-surgery group, a nonsignificant difference. Disease-free 5-year survival in the short-interval group was 44%, compared with 36% in the delayed group.

"The timing of surgery, both as a continuous and a dichotomous variable, was not associated" with perioperative complication or death, pathological complete response, or overall survival, Dr. Kim added.

On multivariable analysis, older age, more involved lymph nodes, and advanced pathological stage were independently associated with decreased survival.

The researchers performed a subgroup analysis of patients with adenocarcinoma histology and found that the results were similar.

Dr. Kim said that he had no relevant financial disclosures.

SAN DIEGO – An interval between neoadjuvant chemoradiation and esophagectomy that extends beyond 8 weeks is not associated with increased perioperative complications, increased pathological complete response, or change in overall survival, results from a long-term single-center study showed.

"For patients who have not yet recovered from neoadjuvant chemoradiation, it is safe to delay surgery to allow them to improve their performance status," Dr. Jae Y. Kim said at the annual meeting of the Society of Thoracic Surgeons.

Traditionally, he said, surgery has been recommended within 8 weeks after completing neoadjuvant chemoradiation for esophageal cancer, yet many patients choose to delay their surgery.

Some patients have not yet recovered from chemoradiation, while others are delayed for personal or logistical reasons, explained Dr. Kim, a thoracic surgery fellow at the University of Texas M.D. Anderson Cancer Center, Houston. "The impact of this delay on outcomes is unknown." Radiation-induced tumor necrosis increases over time, he said, and there is evidence from rectal cancer that a longer interval may increase the rate of pathological complete response. "On the other hand, there are theoretical concerns that this delay may lead to increased radiation fibrosis and cause a more difficult operation. It is also possible that a delay would allow for tumor regrowth."

In an effort to determine whether an increased interval between chemoradiation and surgery is associated with risk of major perioperative complications or overall survival, Dr. Kim and his associates conducted a retrospective study of 266 patients with esophageal cancer followed by neoadjuvant chemoradiation who were treated at M.D. Anderson in 2002-2008. They divided the patients into two groups: a "short-interval" group of 150 who underwent esophagectomy within 8 weeks of chemoradiation, and a "delayed" group of 116 who underwent esophagectomy more than 8 weeks following chemoradiation.

"Most patients were clustered around 4-11 weeks," Dr. Kim said. "No patient had surgery more than 46 weeks after completing neoadjuvant chemoradiation."

The median interval from completion of neoadjuvant therapy to surgery was 46 days in the short-interval group and 76 days in the delayed group. In both groups, more than 95% of patients were staged with PET-CT and endoscopic ultrasound.

The researchers compared the two groups in terms of perioperative complications, rate of pathological complete response, and overall survival.

The two groups were similar in 18 of 22 baseline characteristics examined, but they were different in four areas. Compared with their counterparts in the short-interval group, the patients in the delayed group were slightly older (mean age, 60 years vs. 57 years, respectively), had more coronary artery disease (17% vs. 7%), had less adenocarcinoma histology (87% vs. 97%), and weighed less (53% with a body mass index of 25 kg/m2 or greater vs. 75% of their counterparts in the short-interval group).

By any objective measure used to gauge the difficulty of the operation, the two groups were similar, including mean OR time (390 minutes in the short-interval group vs. 398 minutes in the delayed group), mean number of lymph nodes removed (21% vs. 20%), and mean estimated blood loss (505 mL vs. 478 mL).

The rates of major complications also were similar between the two groups, including perioperative mortality (2% in the short-interval group vs. 3% in the delayed group), median length of stay (11 days in each group), and rate of anastomotic leak (11% vs. 16%).

The rate of pathological complete response was similar between the two groups (21% vs. 23%).

Overall 5-year survival in the short-interval group was 46%, compared with 36% in the delayed-surgery group, a nonsignificant difference. Disease-free 5-year survival in the short-interval group was 44%, compared with 36% in the delayed group.

"The timing of surgery, both as a continuous and a dichotomous variable, was not associated" with perioperative complication or death, pathological complete response, or overall survival, Dr. Kim added.

On multivariable analysis, older age, more involved lymph nodes, and advanced pathological stage were independently associated with decreased survival.

The researchers performed a subgroup analysis of patients with adenocarcinoma histology and found that the results were similar.

Dr. Kim said that he had no relevant financial disclosures.

SAN DIEGO – Findings from studies recently completed or nearing completion should help better inform clinicians about the use of an anticoagulation strategy for patients with sepsis, Dr. Steven P. LaRosa said at the annual congress of the Society of Critical Care Medicine.

"There are multiple reasons why one would think that an anticoagulant drug may be effective in sepsis," said Dr. LaRosa, director of the Ocean State Clinical Coordinating Center at Rhode Island Hospital, Providence. "Cytokine release can cause the elaboration of tissue factor and the activation of the coagulation system, resulting in fibrin formation. Endogenous anticoagulants such as antithrombin and activated protein C [APC] are rapidly consumed and depleted, losing another homeostatic mechanism. Fibrinolysis is impaired through the activation of plasminogen activator inhibitor-1."

The APC drotrecogin alfa (activated) (Xigris) has been approved for severe sepsis since 2001, but its effectiveness is in question, Dr. LaRosa said. Subgroup analysis from the randomized, placebo-controlled, phase III clinical trial of Xigris versus placebo found that patients with vasopressor-dependent shock and one sign of organ hypoperfusion had a greater than 7% absolute reduction in mortality with Xigris use (Intensive Care Med. 2008;34:1935-47). This supported findings from an earlier human endotoxin challenge model of APC (Shock 2004;21:222-9). In that model, "the only real effect we saw with APC was maintenance of blood pressure in the volunteers who received APC compared with placebo," said Dr. LaRosa, who is also assistant professor of medicine at Brown University’s Alpert Medical School in Providence.

These developments led to the PROWESS-SHOCK trial, a confirmatory study that is enrolling patients with septic shock who require vasopressors despite adequate fluid resuscitation and who have associated hypoperfusion. The study was initially sized at 1,500 patients, Dr. LaRosa said, "but the size had to be increased because of a low aggregate mortality. The trial is expected to end sometime in the summer of 2011."

A study presented at a poster session by Dr. LaRosa and Dr. Andre Kalil of the same center examined all of the observational cohort studies that have been done since the approval of Xigris for sepsis. Combined, the studies enrolled more than 42,000 patients. "We saw a 17% relative risk reduction with APC, which was highly statistically significant," Dr. LaRosa reported. "So while we’re waiting for the randomized, controlled confirmatory trial, I think the observational trials do give us some assistance in deciding on the use of the drug."

Another anticoagulation strategy for sepsis patients involves the use of recombinant soluble thrombomodulin (ART-123). Manufactured by Artisan Pharma and currently available for use in Japan, ART-123 "is a thrombin scavenger and an activator of APC," Dr. LaRosa said. "It also blocks high-mobility group protein B1’s binding to the receptor for advanced glycation endoproducts, and it has multiple effects of inhibiting the complement cascade."

In a phase II, placebo-controlled trial, 234 patients received ART-123 0.06 mg/kg over 30 minutes once daily or heparin 8 U/kg per hour for 24 hours (J. Thromb. Haemost. 2007;5:31-41). They were treated for 6 days. "These were all-comers with disseminated intravascular coagulation [DIC] due to malignancy or infection," Dr. LaRosa said. "The treatment effect resided in patients with infection-induced DIC, such that they had a greater than 6% absolute reduction in mortality."

This led to a larger phase II study that enrolled 750 patients. The trial was completed in April 2010, but the results are not yet available, Dr. LaRosa said.

Another molecule starting to be targeted clinically in humans with sepsis is vascular endothelial growth factor (VEGF). This molecule "clearly increases vascular dilation and permeability, induces the expression of cell adhesion molecules, and upregulates tissue factor RNA," Dr. LaRosa said. "High levels of VEGF in humans with sepsis correlate with increased vascular permeability, poor outcome, and disease severity."

In February 2010 a multicenter trial of bevacizumab (Avastin) was launched in 20 patients with septic shock. Bevacizumab is a humanized monoclonal antibody directed against VEGF. "This drug binds to VEGF and impairs angiogenesis," he said. "It’s approved for use in breast, lung, and colon cancer. It has a long half-life, and its chief side effect is hypertension."

The patients received placebo or bevacizumab IV 10 mg/kg over the course of 90 minutes. "The estimated completion date was January 2011, so the results are not yet available," he said.

P2Y12 ADP-receptor antagonists may also play a role in the future of care for sepsis patients. A placebo-controlled, healthy human endotoxin challenge model with prasugrel was launched in November 2009 to examine coagulation activation and platelet-leukocyte interactions, Dr. LaRosa said. The trial was to be completed in June 2010, but its results have not yet been reported.

Dr. LaRosa disclosed that he has received consulting honoraria from Artisan Pharma.

SAN DIEGO – Findings from studies recently completed or nearing completion should help better inform clinicians about the use of an anticoagulation strategy for patients with sepsis, Dr. Steven P. LaRosa said at the annual congress of the Society of Critical Care Medicine.

"There are multiple reasons why one would think that an anticoagulant drug may be effective in sepsis," said Dr. LaRosa, director of the Ocean State Clinical Coordinating Center at Rhode Island Hospital, Providence. "Cytokine release can cause the elaboration of tissue factor and the activation of the coagulation system, resulting in fibrin formation. Endogenous anticoagulants such as antithrombin and activated protein C [APC] are rapidly consumed and depleted, losing another homeostatic mechanism. Fibrinolysis is impaired through the activation of plasminogen activator inhibitor-1."

The APC drotrecogin alfa (activated) (Xigris) has been approved for severe sepsis since 2001, but its effectiveness is in question, Dr. LaRosa said. Subgroup analysis from the randomized, placebo-controlled, phase III clinical trial of Xigris versus placebo found that patients with vasopressor-dependent shock and one sign of organ hypoperfusion had a greater than 7% absolute reduction in mortality with Xigris use (Intensive Care Med. 2008;34:1935-47). This supported findings from an earlier human endotoxin challenge model of APC (Shock 2004;21:222-9). In that model, "the only real effect we saw with APC was maintenance of blood pressure in the volunteers who received APC compared with placebo," said Dr. LaRosa, who is also assistant professor of medicine at Brown University’s Alpert Medical School in Providence.

These developments led to the PROWESS-SHOCK trial, a confirmatory study that is enrolling patients with septic shock who require vasopressors despite adequate fluid resuscitation and who have associated hypoperfusion. The study was initially sized at 1,500 patients, Dr. LaRosa said, "but the size had to be increased because of a low aggregate mortality. The trial is expected to end sometime in the summer of 2011."

A study presented at a poster session by Dr. LaRosa and Dr. Andre Kalil of the same center examined all of the observational cohort studies that have been done since the approval of Xigris for sepsis. Combined, the studies enrolled more than 42,000 patients. "We saw a 17% relative risk reduction with APC, which was highly statistically significant," Dr. LaRosa reported. "So while we’re waiting for the randomized, controlled confirmatory trial, I think the observational trials do give us some assistance in deciding on the use of the drug."

Another anticoagulation strategy for sepsis patients involves the use of recombinant soluble thrombomodulin (ART-123). Manufactured by Artisan Pharma and currently available for use in Japan, ART-123 "is a thrombin scavenger and an activator of APC," Dr. LaRosa said. "It also blocks high-mobility group protein B1’s binding to the receptor for advanced glycation endoproducts, and it has multiple effects of inhibiting the complement cascade."

In a phase II, placebo-controlled trial, 234 patients received ART-123 0.06 mg/kg over 30 minutes once daily or heparin 8 U/kg per hour for 24 hours (J. Thromb. Haemost. 2007;5:31-41). They were treated for 6 days. "These were all-comers with disseminated intravascular coagulation [DIC] due to malignancy or infection," Dr. LaRosa said. "The treatment effect resided in patients with infection-induced DIC, such that they had a greater than 6% absolute reduction in mortality."

This led to a larger phase II study that enrolled 750 patients. The trial was completed in April 2010, but the results are not yet available, Dr. LaRosa said.

Another molecule starting to be targeted clinically in humans with sepsis is vascular endothelial growth factor (VEGF). This molecule "clearly increases vascular dilation and permeability, induces the expression of cell adhesion molecules, and upregulates tissue factor RNA," Dr. LaRosa said. "High levels of VEGF in humans with sepsis correlate with increased vascular permeability, poor outcome, and disease severity."

In February 2010 a multicenter trial of bevacizumab (Avastin) was launched in 20 patients with septic shock. Bevacizumab is a humanized monoclonal antibody directed against VEGF. "This drug binds to VEGF and impairs angiogenesis," he said. "It’s approved for use in breast, lung, and colon cancer. It has a long half-life, and its chief side effect is hypertension."

The patients received placebo or bevacizumab IV 10 mg/kg over the course of 90 minutes. "The estimated completion date was January 2011, so the results are not yet available," he said.

P2Y12 ADP-receptor antagonists may also play a role in the future of care for sepsis patients. A placebo-controlled, healthy human endotoxin challenge model with prasugrel was launched in November 2009 to examine coagulation activation and platelet-leukocyte interactions, Dr. LaRosa said. The trial was to be completed in June 2010, but its results have not yet been reported.

Dr. LaRosa disclosed that he has received consulting honoraria from Artisan Pharma.

SAN DIEGO – Findings from studies recently completed or nearing completion should help better inform clinicians about the use of an anticoagulation strategy for patients with sepsis, Dr. Steven P. LaRosa said at the annual congress of the Society of Critical Care Medicine.

"There are multiple reasons why one would think that an anticoagulant drug may be effective in sepsis," said Dr. LaRosa, director of the Ocean State Clinical Coordinating Center at Rhode Island Hospital, Providence. "Cytokine release can cause the elaboration of tissue factor and the activation of the coagulation system, resulting in fibrin formation. Endogenous anticoagulants such as antithrombin and activated protein C [APC] are rapidly consumed and depleted, losing another homeostatic mechanism. Fibrinolysis is impaired through the activation of plasminogen activator inhibitor-1."

The APC drotrecogin alfa (activated) (Xigris) has been approved for severe sepsis since 2001, but its effectiveness is in question, Dr. LaRosa said. Subgroup analysis from the randomized, placebo-controlled, phase III clinical trial of Xigris versus placebo found that patients with vasopressor-dependent shock and one sign of organ hypoperfusion had a greater than 7% absolute reduction in mortality with Xigris use (Intensive Care Med. 2008;34:1935-47). This supported findings from an earlier human endotoxin challenge model of APC (Shock 2004;21:222-9). In that model, "the only real effect we saw with APC was maintenance of blood pressure in the volunteers who received APC compared with placebo," said Dr. LaRosa, who is also assistant professor of medicine at Brown University’s Alpert Medical School in Providence.

These developments led to the PROWESS-SHOCK trial, a confirmatory study that is enrolling patients with septic shock who require vasopressors despite adequate fluid resuscitation and who have associated hypoperfusion. The study was initially sized at 1,500 patients, Dr. LaRosa said, "but the size had to be increased because of a low aggregate mortality. The trial is expected to end sometime in the summer of 2011."

A study presented at a poster session by Dr. LaRosa and Dr. Andre Kalil of the same center examined all of the observational cohort studies that have been done since the approval of Xigris for sepsis. Combined, the studies enrolled more than 42,000 patients. "We saw a 17% relative risk reduction with APC, which was highly statistically significant," Dr. LaRosa reported. "So while we’re waiting for the randomized, controlled confirmatory trial, I think the observational trials do give us some assistance in deciding on the use of the drug."

Another anticoagulation strategy for sepsis patients involves the use of recombinant soluble thrombomodulin (ART-123). Manufactured by Artisan Pharma and currently available for use in Japan, ART-123 "is a thrombin scavenger and an activator of APC," Dr. LaRosa said. "It also blocks high-mobility group protein B1’s binding to the receptor for advanced glycation endoproducts, and it has multiple effects of inhibiting the complement cascade."

In a phase II, placebo-controlled trial, 234 patients received ART-123 0.06 mg/kg over 30 minutes once daily or heparin 8 U/kg per hour for 24 hours (J. Thromb. Haemost. 2007;5:31-41). They were treated for 6 days. "These were all-comers with disseminated intravascular coagulation [DIC] due to malignancy or infection," Dr. LaRosa said. "The treatment effect resided in patients with infection-induced DIC, such that they had a greater than 6% absolute reduction in mortality."

This led to a larger phase II study that enrolled 750 patients. The trial was completed in April 2010, but the results are not yet available, Dr. LaRosa said.

Another molecule starting to be targeted clinically in humans with sepsis is vascular endothelial growth factor (VEGF). This molecule "clearly increases vascular dilation and permeability, induces the expression of cell adhesion molecules, and upregulates tissue factor RNA," Dr. LaRosa said. "High levels of VEGF in humans with sepsis correlate with increased vascular permeability, poor outcome, and disease severity."

In February 2010 a multicenter trial of bevacizumab (Avastin) was launched in 20 patients with septic shock. Bevacizumab is a humanized monoclonal antibody directed against VEGF. "This drug binds to VEGF and impairs angiogenesis," he said. "It’s approved for use in breast, lung, and colon cancer. It has a long half-life, and its chief side effect is hypertension."

The patients received placebo or bevacizumab IV 10 mg/kg over the course of 90 minutes. "The estimated completion date was January 2011, so the results are not yet available," he said.

P2Y12 ADP-receptor antagonists may also play a role in the future of care for sepsis patients. A placebo-controlled, healthy human endotoxin challenge model with prasugrel was launched in November 2009 to examine coagulation activation and platelet-leukocyte interactions, Dr. LaRosa said. The trial was to be completed in June 2010, but its results have not yet been reported.

Dr. LaRosa disclosed that he has received consulting honoraria from Artisan Pharma.

SAN DIEGO – Findings from studies recently completed or nearing completion should help better inform clinicians about the use of an anticoagulation strategy for patients with sepsis, Dr. Steven P. LaRosa said at the annual congress of the Society of Critical Care Medicine.

"There are multiple reasons why one would think that an anticoagulant drug may be effective in sepsis," said Dr. LaRosa, director of the Ocean State Clinical Coordinating Center at Rhode Island Hospital, Providence. "Cytokine release can cause the elaboration of tissue factor and the activation of the coagulation system, resulting in fibrin formation. Endogenous anticoagulants such as antithrombin and activated protein C [APC] are rapidly consumed and depleted, losing another homeostatic mechanism. Fibrinolysis is impaired through the activation of plasminogen activator inhibitor-1."

The APC drotrecogin alfa (activated) (Xigris) has been approved for severe sepsis since 2001, but its effectiveness is in question, Dr. LaRosa said. Subgroup analysis from the randomized, placebo-controlled, phase III clinical trial of Xigris versus placebo found that patients with vasopressor-dependent shock and one sign of organ hypoperfusion had a greater than 7% absolute reduction in mortality with Xigris use (Intensive Care Med. 2008;34:1935-47). This supported findings from an earlier human endotoxin challenge model of APC (Shock 2004;21:222-9). In that model, "the only real effect we saw with APC was maintenance of blood pressure in the volunteers who received APC compared with placebo," said Dr. LaRosa, who is also assistant professor of medicine at Brown University’s Alpert Medical School in Providence.

These developments led to the PROWESS-SHOCK trial, a confirmatory study that is enrolling patients with septic shock who require vasopressors despite adequate fluid resuscitation and who have associated hypoperfusion. The study was initially sized at 1,500 patients, Dr. LaRosa said, "but the size had to be increased because of a low aggregate mortality. The trial is expected to end sometime in the summer of 2011."

A study presented at a poster session by Dr. LaRosa and Dr. Andre Kalil of the same center examined all of the observational cohort studies that have been done since the approval of Xigris for sepsis. Combined, the studies enrolled more than 42,000 patients. "We saw a 17% relative risk reduction with APC, which was highly statistically significant," Dr. LaRosa reported. "So while we’re waiting for the randomized, controlled confirmatory trial, I think the observational trials do give us some assistance in deciding on the use of the drug."

Another anticoagulation strategy for sepsis patients involves the use of recombinant soluble thrombomodulin (ART-123). Manufactured by Artisan Pharma and currently available for use in Japan, ART-123 "is a thrombin scavenger and an activator of APC," Dr. LaRosa said. "It also blocks high-mobility group protein B1’s binding to the receptor for advanced glycation endoproducts, and it has multiple effects of inhibiting the complement cascade."

In a phase II, placebo-controlled trial, 234 patients received ART-123 0.06 mg/kg over 30 minutes once daily or heparin 8 U/kg per hour for 24 hours (J. Thromb. Haemost. 2007;5:31-41). They were treated for 6 days. "These were all-comers with disseminated intravascular coagulation [DIC] due to malignancy or infection," Dr. LaRosa said. "The treatment effect resided in patients with infection-induced DIC, such that they had a greater than 6% absolute reduction in mortality."

This led to a larger phase II study that enrolled 750 patients. The trial was completed in April 2010, but the results are not yet available, Dr. LaRosa said.

Another molecule starting to be targeted clinically in humans with sepsis is vascular endothelial growth factor (VEGF). This molecule "clearly increases vascular dilation and permeability, induces the expression of cell adhesion molecules, and upregulates tissue factor RNA," Dr. LaRosa said. "High levels of VEGF in humans with sepsis correlate with increased vascular permeability, poor outcome, and disease severity."

In February 2010 a multicenter trial of bevacizumab (Avastin) was launched in 20 patients with septic shock. Bevacizumab is a humanized monoclonal antibody directed against VEGF. "This drug binds to VEGF and impairs angiogenesis," he said. "It’s approved for use in breast, lung, and colon cancer. It has a long half-life, and its chief side effect is hypertension."

The patients received placebo or bevacizumab IV 10 mg/kg over the course of 90 minutes. "The estimated completion date was January 2011, so the results are not yet available," he said.

P2Y12 ADP-receptor antagonists may also play a role in the future of care for sepsis patients. A placebo-controlled, healthy human endotoxin challenge model with prasugrel was launched in November 2009 to examine coagulation activation and platelet-leukocyte interactions, Dr. LaRosa said. The trial was to be completed in June 2010, but its results have not yet been reported.

Dr. LaRosa disclosed that he has received consulting honoraria from Artisan Pharma.

SAN DIEGO – Findings from studies recently completed or nearing completion should help better inform clinicians about the use of an anticoagulation strategy for patients with sepsis, Dr. Steven P. LaRosa said at the annual congress of the Society of Critical Care Medicine.

"There are multiple reasons why one would think that an anticoagulant drug may be effective in sepsis," said Dr. LaRosa, director of the Ocean State Clinical Coordinating Center at Rhode Island Hospital, Providence. "Cytokine release can cause the elaboration of tissue factor and the activation of the coagulation system, resulting in fibrin formation. Endogenous anticoagulants such as antithrombin and activated protein C [APC] are rapidly consumed and depleted, losing another homeostatic mechanism. Fibrinolysis is impaired through the activation of plasminogen activator inhibitor-1."

The APC drotrecogin alfa (activated) (Xigris) has been approved for severe sepsis since 2001, but its effectiveness is in question, Dr. LaRosa said. Subgroup analysis from the randomized, placebo-controlled, phase III clinical trial of Xigris versus placebo found that patients with vasopressor-dependent shock and one sign of organ hypoperfusion had a greater than 7% absolute reduction in mortality with Xigris use (Intensive Care Med. 2008;34:1935-47). This supported findings from an earlier human endotoxin challenge model of APC (Shock 2004;21:222-9). In that model, "the only real effect we saw with APC was maintenance of blood pressure in the volunteers who received APC compared with placebo," said Dr. LaRosa, who is also assistant professor of medicine at Brown University’s Alpert Medical School in Providence.

These developments led to the PROWESS-SHOCK trial, a confirmatory study that is enrolling patients with septic shock who require vasopressors despite adequate fluid resuscitation and who have associated hypoperfusion. The study was initially sized at 1,500 patients, Dr. LaRosa said, "but the size had to be increased because of a low aggregate mortality. The trial is expected to end sometime in the summer of 2011."

A study presented at a poster session by Dr. LaRosa and Dr. Andre Kalil of the same center examined all of the observational cohort studies that have been done since the approval of Xigris for sepsis. Combined, the studies enrolled more than 42,000 patients. "We saw a 17% relative risk reduction with APC, which was highly statistically significant," Dr. LaRosa reported. "So while we’re waiting for the randomized, controlled confirmatory trial, I think the observational trials do give us some assistance in deciding on the use of the drug."

Another anticoagulation strategy for sepsis patients involves the use of recombinant soluble thrombomodulin (ART-123). Manufactured by Artisan Pharma and currently available for use in Japan, ART-123 "is a thrombin scavenger and an activator of APC," Dr. LaRosa said. "It also blocks high-mobility group protein B1’s binding to the receptor for advanced glycation endoproducts, and it has multiple effects of inhibiting the complement cascade."

In a phase II, placebo-controlled trial, 234 patients received ART-123 0.06 mg/kg over 30 minutes once daily or heparin 8 U/kg per hour for 24 hours (J. Thromb. Haemost. 2007;5:31-41). They were treated for 6 days. "These were all-comers with disseminated intravascular coagulation [DIC] due to malignancy or infection," Dr. LaRosa said. "The treatment effect resided in patients with infection-induced DIC, such that they had a greater than 6% absolute reduction in mortality."

This led to a larger phase II study that enrolled 750 patients. The trial was completed in April 2010, but the results are not yet available, Dr. LaRosa said.

Another molecule starting to be targeted clinically in humans with sepsis is vascular endothelial growth factor (VEGF). This molecule "clearly increases vascular dilation and permeability, induces the expression of cell adhesion molecules, and upregulates tissue factor RNA," Dr. LaRosa said. "High levels of VEGF in humans with sepsis correlate with increased vascular permeability, poor outcome, and disease severity."

In February 2010 a multicenter trial of bevacizumab (Avastin) was launched in 20 patients with septic shock. Bevacizumab is a humanized monoclonal antibody directed against VEGF. "This drug binds to VEGF and impairs angiogenesis," he said. "It’s approved for use in breast, lung, and colon cancer. It has a long half-life, and its chief side effect is hypertension."

The patients received placebo or bevacizumab IV 10 mg/kg over the course of 90 minutes. "The estimated completion date was January 2011, so the results are not yet available," he said.

P2Y12 ADP-receptor antagonists may also play a role in the future of care for sepsis patients. A placebo-controlled, healthy human endotoxin challenge model with prasugrel was launched in November 2009 to examine coagulation activation and platelet-leukocyte interactions, Dr. LaRosa said. The trial was to be completed in June 2010, but its results have not yet been reported.

Dr. LaRosa disclosed that he has received consulting honoraria from Artisan Pharma.

SAN DIEGO – Findings from studies recently completed or nearing completion should help better inform clinicians about the use of an anticoagulation strategy for patients with sepsis, Dr. Steven P. LaRosa said at the annual congress of the Society of Critical Care Medicine.

"There are multiple reasons why one would think that an anticoagulant drug may be effective in sepsis," said Dr. LaRosa, director of the Ocean State Clinical Coordinating Center at Rhode Island Hospital, Providence. "Cytokine release can cause the elaboration of tissue factor and the activation of the coagulation system, resulting in fibrin formation. Endogenous anticoagulants such as antithrombin and activated protein C [APC] are rapidly consumed and depleted, losing another homeostatic mechanism. Fibrinolysis is impaired through the activation of plasminogen activator inhibitor-1."

The APC drotrecogin alfa (activated) (Xigris) has been approved for severe sepsis since 2001, but its effectiveness is in question, Dr. LaRosa said. Subgroup analysis from the randomized, placebo-controlled, phase III clinical trial of Xigris versus placebo found that patients with vasopressor-dependent shock and one sign of organ hypoperfusion had a greater than 7% absolute reduction in mortality with Xigris use (Intensive Care Med. 2008;34:1935-47). This supported findings from an earlier human endotoxin challenge model of APC (Shock 2004;21:222-9). In that model, "the only real effect we saw with APC was maintenance of blood pressure in the volunteers who received APC compared with placebo," said Dr. LaRosa, who is also assistant professor of medicine at Brown University’s Alpert Medical School in Providence.

These developments led to the PROWESS-SHOCK trial, a confirmatory study that is enrolling patients with septic shock who require vasopressors despite adequate fluid resuscitation and who have associated hypoperfusion. The study was initially sized at 1,500 patients, Dr. LaRosa said, "but the size had to be increased because of a low aggregate mortality. The trial is expected to end sometime in the summer of 2011."

A study presented at a poster session by Dr. LaRosa and Dr. Andre Kalil of the same center examined all of the observational cohort studies that have been done since the approval of Xigris for sepsis. Combined, the studies enrolled more than 42,000 patients. "We saw a 17% relative risk reduction with APC, which was highly statistically significant," Dr. LaRosa reported. "So while we’re waiting for the randomized, controlled confirmatory trial, I think the observational trials do give us some assistance in deciding on the use of the drug."

Another anticoagulation strategy for sepsis patients involves the use of recombinant soluble thrombomodulin (ART-123). Manufactured by Artisan Pharma and currently available for use in Japan, ART-123 "is a thrombin scavenger and an activator of APC," Dr. LaRosa said. "It also blocks high-mobility group protein B1’s binding to the receptor for advanced glycation endoproducts, and it has multiple effects of inhibiting the complement cascade."

In a phase II, placebo-controlled trial, 234 patients received ART-123 0.06 mg/kg over 30 minutes once daily or heparin 8 U/kg per hour for 24 hours (J. Thromb. Haemost. 2007;5:31-41). They were treated for 6 days. "These were all-comers with disseminated intravascular coagulation [DIC] due to malignancy or infection," Dr. LaRosa said. "The treatment effect resided in patients with infection-induced DIC, such that they had a greater than 6% absolute reduction in mortality."

This led to a larger phase II study that enrolled 750 patients. The trial was completed in April 2010, but the results are not yet available, Dr. LaRosa said.

Another molecule starting to be targeted clinically in humans with sepsis is vascular endothelial growth factor (VEGF). This molecule "clearly increases vascular dilation and permeability, induces the expression of cell adhesion molecules, and upregulates tissue factor RNA," Dr. LaRosa said. "High levels of VEGF in humans with sepsis correlate with increased vascular permeability, poor outcome, and disease severity."

In February 2010 a multicenter trial of bevacizumab (Avastin) was launched in 20 patients with septic shock. Bevacizumab is a humanized monoclonal antibody directed against VEGF. "This drug binds to VEGF and impairs angiogenesis," he said. "It’s approved for use in breast, lung, and colon cancer. It has a long half-life, and its chief side effect is hypertension."

The patients received placebo or bevacizumab IV 10 mg/kg over the course of 90 minutes. "The estimated completion date was January 2011, so the results are not yet available," he said.

P2Y12 ADP-receptor antagonists may also play a role in the future of care for sepsis patients. A placebo-controlled, healthy human endotoxin challenge model with prasugrel was launched in November 2009 to examine coagulation activation and platelet-leukocyte interactions, Dr. LaRosa said. The trial was to be completed in June 2010, but its results have not yet been reported.

Dr. LaRosa disclosed that he has received consulting honoraria from Artisan Pharma.