ACS Surgery News

LAS VEGAS – The number of hysterectomies in the United States appears to be on the decline, despite a 10% increase in minimally invasive cases.

Based on updated surveillance data, an estimated 479,229 hysterectomies were performed in the United States in 2009, of which 24% used a laparoscopic approach.

Patrice Wendling/IMNG Medical Media

By comparison, there were 518,828 hysterectomies in 2005, 14% of which were laparoscopic: 64% were abdominal and 22% were vaginal (Obstet. Gynecol. 2009;114:1041-8).

Whether this represents a real decline in hysterectomies is unclear, Dr. Sarah Cohen of Brigham and Women’s Hospital in Boston said at the 41st AAGL Global Congress.

The current analysis included oncologic cases, whereas the 2005 analysis looked only at gynecologic hysterectomies for benign disease.

On the other hand, both analyses are based on the Nationwide Inpatient Sample (NIS), which represents a 20% stratified random sample of discharges from all community hospitals in the United States. It is the largest national all-payer database of hospital discharges, but that’s where it stops.

"It’s possible that there are a number of nonsurgical options being offered to patients; however, I do think this also represents the increase in outpatient surgeries being offered, and the Nationwide Inpatient Sample databases aren’t able to account for those," she said. "Particularly, we may be underestimating laparoscopic and vaginal procedures that are being done in ambulatory settings."

Hysterectomy is the most common nonobstetric surgical procedure among women, with 600,000 typically cited as the annual number of procedures.

Dr. Cohen and her colleagues sought to verify this number using ICD-9 codes in the 2009 NIS – the most recent year available – to abstract information about any patient who underwent a hysterectomy during her hospitalization, including oncologic cases. Obstetric hysterectomies were excluded. The data were then weighted to give national estimates.

The mean patient age was 48 years, and the predominant indications were uterine fibroids (47%) and menstrual disorders (45%). Adnexal surgery occurred in 57% of cases.

Abdominal hysterectomy made up 58% of cases and vaginal hysterectomy 17% in the updated analysis, compared with 64% and 22% in the 2005 NIS, Dr. Cohen said.

In regression analysis, factors associated with laparoscopic surgery compared with abdominal surgery were younger age, white race, an indication of prolapse, menstrual disorder or endometriosis, living in an urban area, having a high income, having private insurance, and living in the Western United States.

When the regressions were repeated to compare laparoscopic with vaginal surgery, factors favoring the laparoscopic approach were age 40-49, black race, any nonprolapse indication, concomitant adnexal surgery, living in an urban area, having a high income, having private insurance, and living in the Northeastern United States.

Based on a systematic review of the literature, seven articles have been published in the past 5 years regarding hysterectomy surveillance, Dr. Cohen observed.

Although the NIS database may be incomplete, the bidirectional trends of falling overall numbers and rising laparoscopic procedures appear to be holding. An analysis of the 2003 NIS revealed 602,457 hysterectomies, with the abdominal route the most common at 66%, followed by the vaginal (22%) and laparoscopic (12%) routes (Obstet. Gynecol. 2007;110:1091-5).

Dr. Cohen said it’s critical to continue evaluating trends in hysterectomy performance, particularly with increasing outpatient minimally invasive procedures, and that he and his colleagues plan to incorporate state-level ambulatory surgery databases to capture outpatient procedures. They also will perform subgroup analyses of benign and oncologic cases, and look at factors associated with concomitant adnexal procedures.

Dr. Cohen reported no relevant financial disclosures.

LAS VEGAS – The number of hysterectomies in the United States appears to be on the decline, despite a 10% increase in minimally invasive cases.

Based on updated surveillance data, an estimated 479,229 hysterectomies were performed in the United States in 2009, of which 24% used a laparoscopic approach.

Patrice Wendling/IMNG Medical Media

By comparison, there were 518,828 hysterectomies in 2005, 14% of which were laparoscopic: 64% were abdominal and 22% were vaginal (Obstet. Gynecol. 2009;114:1041-8).

Whether this represents a real decline in hysterectomies is unclear, Dr. Sarah Cohen of Brigham and Women’s Hospital in Boston said at the 41st AAGL Global Congress.

The current analysis included oncologic cases, whereas the 2005 analysis looked only at gynecologic hysterectomies for benign disease.

On the other hand, both analyses are based on the Nationwide Inpatient Sample (NIS), which represents a 20% stratified random sample of discharges from all community hospitals in the United States. It is the largest national all-payer database of hospital discharges, but that’s where it stops.

"It’s possible that there are a number of nonsurgical options being offered to patients; however, I do think this also represents the increase in outpatient surgeries being offered, and the Nationwide Inpatient Sample databases aren’t able to account for those," she said. "Particularly, we may be underestimating laparoscopic and vaginal procedures that are being done in ambulatory settings."

Hysterectomy is the most common nonobstetric surgical procedure among women, with 600,000 typically cited as the annual number of procedures.

Dr. Cohen and her colleagues sought to verify this number using ICD-9 codes in the 2009 NIS – the most recent year available – to abstract information about any patient who underwent a hysterectomy during her hospitalization, including oncologic cases. Obstetric hysterectomies were excluded. The data were then weighted to give national estimates.

The mean patient age was 48 years, and the predominant indications were uterine fibroids (47%) and menstrual disorders (45%). Adnexal surgery occurred in 57% of cases.

Abdominal hysterectomy made up 58% of cases and vaginal hysterectomy 17% in the updated analysis, compared with 64% and 22% in the 2005 NIS, Dr. Cohen said.

In regression analysis, factors associated with laparoscopic surgery compared with abdominal surgery were younger age, white race, an indication of prolapse, menstrual disorder or endometriosis, living in an urban area, having a high income, having private insurance, and living in the Western United States.

When the regressions were repeated to compare laparoscopic with vaginal surgery, factors favoring the laparoscopic approach were age 40-49, black race, any nonprolapse indication, concomitant adnexal surgery, living in an urban area, having a high income, having private insurance, and living in the Northeastern United States.

Based on a systematic review of the literature, seven articles have been published in the past 5 years regarding hysterectomy surveillance, Dr. Cohen observed.

Although the NIS database may be incomplete, the bidirectional trends of falling overall numbers and rising laparoscopic procedures appear to be holding. An analysis of the 2003 NIS revealed 602,457 hysterectomies, with the abdominal route the most common at 66%, followed by the vaginal (22%) and laparoscopic (12%) routes (Obstet. Gynecol. 2007;110:1091-5).

Dr. Cohen said it’s critical to continue evaluating trends in hysterectomy performance, particularly with increasing outpatient minimally invasive procedures, and that he and his colleagues plan to incorporate state-level ambulatory surgery databases to capture outpatient procedures. They also will perform subgroup analyses of benign and oncologic cases, and look at factors associated with concomitant adnexal procedures.

Dr. Cohen reported no relevant financial disclosures.

LAS VEGAS – The number of hysterectomies in the United States appears to be on the decline, despite a 10% increase in minimally invasive cases.

Based on updated surveillance data, an estimated 479,229 hysterectomies were performed in the United States in 2009, of which 24% used a laparoscopic approach.

Patrice Wendling/IMNG Medical Media

By comparison, there were 518,828 hysterectomies in 2005, 14% of which were laparoscopic: 64% were abdominal and 22% were vaginal (Obstet. Gynecol. 2009;114:1041-8).

Whether this represents a real decline in hysterectomies is unclear, Dr. Sarah Cohen of Brigham and Women’s Hospital in Boston said at the 41st AAGL Global Congress.

The current analysis included oncologic cases, whereas the 2005 analysis looked only at gynecologic hysterectomies for benign disease.

On the other hand, both analyses are based on the Nationwide Inpatient Sample (NIS), which represents a 20% stratified random sample of discharges from all community hospitals in the United States. It is the largest national all-payer database of hospital discharges, but that’s where it stops.

"It’s possible that there are a number of nonsurgical options being offered to patients; however, I do think this also represents the increase in outpatient surgeries being offered, and the Nationwide Inpatient Sample databases aren’t able to account for those," she said. "Particularly, we may be underestimating laparoscopic and vaginal procedures that are being done in ambulatory settings."

Hysterectomy is the most common nonobstetric surgical procedure among women, with 600,000 typically cited as the annual number of procedures.

Dr. Cohen and her colleagues sought to verify this number using ICD-9 codes in the 2009 NIS – the most recent year available – to abstract information about any patient who underwent a hysterectomy during her hospitalization, including oncologic cases. Obstetric hysterectomies were excluded. The data were then weighted to give national estimates.

The mean patient age was 48 years, and the predominant indications were uterine fibroids (47%) and menstrual disorders (45%). Adnexal surgery occurred in 57% of cases.

Abdominal hysterectomy made up 58% of cases and vaginal hysterectomy 17% in the updated analysis, compared with 64% and 22% in the 2005 NIS, Dr. Cohen said.

In regression analysis, factors associated with laparoscopic surgery compared with abdominal surgery were younger age, white race, an indication of prolapse, menstrual disorder or endometriosis, living in an urban area, having a high income, having private insurance, and living in the Western United States.

When the regressions were repeated to compare laparoscopic with vaginal surgery, factors favoring the laparoscopic approach were age 40-49, black race, any nonprolapse indication, concomitant adnexal surgery, living in an urban area, having a high income, having private insurance, and living in the Northeastern United States.

Based on a systematic review of the literature, seven articles have been published in the past 5 years regarding hysterectomy surveillance, Dr. Cohen observed.

Although the NIS database may be incomplete, the bidirectional trends of falling overall numbers and rising laparoscopic procedures appear to be holding. An analysis of the 2003 NIS revealed 602,457 hysterectomies, with the abdominal route the most common at 66%, followed by the vaginal (22%) and laparoscopic (12%) routes (Obstet. Gynecol. 2007;110:1091-5).

Dr. Cohen said it’s critical to continue evaluating trends in hysterectomy performance, particularly with increasing outpatient minimally invasive procedures, and that he and his colleagues plan to incorporate state-level ambulatory surgery databases to capture outpatient procedures. They also will perform subgroup analyses of benign and oncologic cases, and look at factors associated with concomitant adnexal procedures.

Dr. Cohen reported no relevant financial disclosures.

BOSTON – Everolimus given with a reduced dose of tacrolimus to liver transplant patients yielded similar rates of acute rejection, graft loss, and death, but better kidney function than standard-dose tacrolimus alone at 2 years in a randomized, open-label, multicenter, controlled trial.

These 2-year results confirm and build on the recently published results of the trial at 1 year (Am. J. Transpl. 2012;12:3008-20), lead investigator Dr. Faouzi Saliba of Paul Brousse Hospital, Villejuif, France, reported at the annual meeting of the American Association for the Study of Liver Diseases.

Since the first study was published 9 years ago documenting a cumulative incidence of chronic renal failure of 28% after 10 years of tacrolimus treatment after liver transplant (N. Engl. J. Med. 2003;349:931-40), another study has reported estimated glomerular filtration rates (eGFRs) of less than 60 mL/min per 1.73 m² (stage 3 chronic kidney failure) for 58% of liver transplant recipients after 5 years of treatment with tacrolimus (Liver Transpl. 2009:15:1083-91).

On the basis of the effectiveness of everolimus in reducing the dose of calcineurin inhibitor needed for immunosuppression without reducing efficacy in patients with de novo kidney transplantation (Am. J. Transpl. 2010;10:1401-13), Dr. Saliba and his coinvestigators conducted the current trial.

Following a 30-day run-in period in which liver transplant recipients received tacrolimus with or without mycophenolate mofetil and prednisone, the investigators randomized 719 patients to three arms: two arms with everolimus 3-8 ng/mL, tacrolimus reduced to 3-5 ng/mL, and prednisone, and a control arm with tacrolimus dosed to a standard 8-12 ng/mL plus prednisone. After 4 months, in one of the reduced-dose arms, tacrolimus was withdrawn and the everolimus dose was increased to 8-10 ng/mL (231 patients), whereas the dose of everolimus was kept constant in the other reduced-dose arm (245 patients) and the dose of tacrolimus was kept the same in the control arm (243 patients). Prednisone could be eliminated at 4 months in any arm. However, enrollment into the tacrolimus withdrawal arm was stopped at the time of conversion to everolimus alone because of a high rate of rejection episodes, and the trial’s protocol was amended to compare efficacy between only the reduced-dose and control arms.

By 2 years, the number of patients who completed the study was similar in both the reduced-dose and control arms (82% vs. 84%, respectively), and similar percentages in each group remained on the study medications at 2 years (58% vs. 68%, respectively).

In each group, recipients were mostly men (74%) and white (80%-86%), with a mean age of 54 years and mean donor age of 49 years. They had a Model for End-Stage Liver Disease score of 19, and eGFRs of about 80 mL/min per 1.73 m².

Mean levels of tacrolimus dropped from 10.5 ng/mL at randomization to 4 ng/mL at 2 years in the dose-reduction arm, compared with 10 ng/mL to 7 ng/mL in the control arm.

At 2 years in the intent-to-treat population, the groups had similar rates of the composite primary end point of treated biopsy-proven acute rejection, graft failure, and death (10.5% in the dose-reduction arm and 12.5% in the control arm). Biopsy-proven acute rejection occurred at a significantly lower rate among dose-reduced patients (6%) than among control patients (13%). All of the episodes of acute rejection in the tacrolimus dose-reduced patients were borderline or mild based on the Banff rejection activity index. However, liver biopsies at 1 and 2 years were only part of the trial’s protocol for hepatitis C virus (HCV)-infected patients. The decision to biopsy was otherwise left up to the physicians of each center.

At 1 year, there appeared to be less fibrosis in patients who received everolimus, Dr. Saliba said in response to a question from the audience. In about half of the 75 HCV-infected patients in the dose-reduction arm, liver biopsies showed less fibrosis of at least stage 1 than in patients with HCV infection in the other group. The investigators are now analyzing 2-year data, he said.

The dose-reduced group maintained significantly better eGFR than the control group, through the duration of the trial, finishing with levels of 66 vs. 78 mL/min per 1.73 m².

Several types of adverse events with an incidence of at least 10% occurred more often in the dose-reduction arm than in the control arm, including leucopenia (13% vs. 5%), peripheral edema (20% vs. 13%), and hypercholesterolemia (11% vs. 4%).

Proteinuria of less than 0.5 g/24 hours occurred in 92%-93% of the patients; none of the patients had severe proteinuria of 3 g/24 hours or more.

One audience member noted that the most important patients to study in this clinical population are those on the borderline of renal failure with low eGFR and elevated creatinine, who would benefit most from improved renal function. Dr. Saliba said that at the time of randomization, the investigators looked at levels of eGFR in each group and over the course of the 2 years, more patients in the standard-dose tacrolimus arm had worsened renal function, whereas many in the dose-reduction arm had improved or at least stable renal function, and few had worsened function.

The study was sponsored by Novartis, which manufactures everolimus. Dr. Saliba reported financial ties to Novartis and Astellas Pharma (manufacturer of tacrolimus), as well as other companies that manufacture drugs used by liver transplant patients. Several other investigators reported financial ties to companies that manufacture antirejection drugs used in liver transplant patients, including Novartis. Three study investigators are employees of Novartis.

BOSTON – Everolimus given with a reduced dose of tacrolimus to liver transplant patients yielded similar rates of acute rejection, graft loss, and death, but better kidney function than standard-dose tacrolimus alone at 2 years in a randomized, open-label, multicenter, controlled trial.

These 2-year results confirm and build on the recently published results of the trial at 1 year (Am. J. Transpl. 2012;12:3008-20), lead investigator Dr. Faouzi Saliba of Paul Brousse Hospital, Villejuif, France, reported at the annual meeting of the American Association for the Study of Liver Diseases.

Since the first study was published 9 years ago documenting a cumulative incidence of chronic renal failure of 28% after 10 years of tacrolimus treatment after liver transplant (N. Engl. J. Med. 2003;349:931-40), another study has reported estimated glomerular filtration rates (eGFRs) of less than 60 mL/min per 1.73 m² (stage 3 chronic kidney failure) for 58% of liver transplant recipients after 5 years of treatment with tacrolimus (Liver Transpl. 2009:15:1083-91).

On the basis of the effectiveness of everolimus in reducing the dose of calcineurin inhibitor needed for immunosuppression without reducing efficacy in patients with de novo kidney transplantation (Am. J. Transpl. 2010;10:1401-13), Dr. Saliba and his coinvestigators conducted the current trial.

Following a 30-day run-in period in which liver transplant recipients received tacrolimus with or without mycophenolate mofetil and prednisone, the investigators randomized 719 patients to three arms: two arms with everolimus 3-8 ng/mL, tacrolimus reduced to 3-5 ng/mL, and prednisone, and a control arm with tacrolimus dosed to a standard 8-12 ng/mL plus prednisone. After 4 months, in one of the reduced-dose arms, tacrolimus was withdrawn and the everolimus dose was increased to 8-10 ng/mL (231 patients), whereas the dose of everolimus was kept constant in the other reduced-dose arm (245 patients) and the dose of tacrolimus was kept the same in the control arm (243 patients). Prednisone could be eliminated at 4 months in any arm. However, enrollment into the tacrolimus withdrawal arm was stopped at the time of conversion to everolimus alone because of a high rate of rejection episodes, and the trial’s protocol was amended to compare efficacy between only the reduced-dose and control arms.

By 2 years, the number of patients who completed the study was similar in both the reduced-dose and control arms (82% vs. 84%, respectively), and similar percentages in each group remained on the study medications at 2 years (58% vs. 68%, respectively).

In each group, recipients were mostly men (74%) and white (80%-86%), with a mean age of 54 years and mean donor age of 49 years. They had a Model for End-Stage Liver Disease score of 19, and eGFRs of about 80 mL/min per 1.73 m².

Mean levels of tacrolimus dropped from 10.5 ng/mL at randomization to 4 ng/mL at 2 years in the dose-reduction arm, compared with 10 ng/mL to 7 ng/mL in the control arm.

At 2 years in the intent-to-treat population, the groups had similar rates of the composite primary end point of treated biopsy-proven acute rejection, graft failure, and death (10.5% in the dose-reduction arm and 12.5% in the control arm). Biopsy-proven acute rejection occurred at a significantly lower rate among dose-reduced patients (6%) than among control patients (13%). All of the episodes of acute rejection in the tacrolimus dose-reduced patients were borderline or mild based on the Banff rejection activity index. However, liver biopsies at 1 and 2 years were only part of the trial’s protocol for hepatitis C virus (HCV)-infected patients. The decision to biopsy was otherwise left up to the physicians of each center.

At 1 year, there appeared to be less fibrosis in patients who received everolimus, Dr. Saliba said in response to a question from the audience. In about half of the 75 HCV-infected patients in the dose-reduction arm, liver biopsies showed less fibrosis of at least stage 1 than in patients with HCV infection in the other group. The investigators are now analyzing 2-year data, he said.

The dose-reduced group maintained significantly better eGFR than the control group, through the duration of the trial, finishing with levels of 66 vs. 78 mL/min per 1.73 m².

Several types of adverse events with an incidence of at least 10% occurred more often in the dose-reduction arm than in the control arm, including leucopenia (13% vs. 5%), peripheral edema (20% vs. 13%), and hypercholesterolemia (11% vs. 4%).

Proteinuria of less than 0.5 g/24 hours occurred in 92%-93% of the patients; none of the patients had severe proteinuria of 3 g/24 hours or more.

One audience member noted that the most important patients to study in this clinical population are those on the borderline of renal failure with low eGFR and elevated creatinine, who would benefit most from improved renal function. Dr. Saliba said that at the time of randomization, the investigators looked at levels of eGFR in each group and over the course of the 2 years, more patients in the standard-dose tacrolimus arm had worsened renal function, whereas many in the dose-reduction arm had improved or at least stable renal function, and few had worsened function.

The study was sponsored by Novartis, which manufactures everolimus. Dr. Saliba reported financial ties to Novartis and Astellas Pharma (manufacturer of tacrolimus), as well as other companies that manufacture drugs used by liver transplant patients. Several other investigators reported financial ties to companies that manufacture antirejection drugs used in liver transplant patients, including Novartis. Three study investigators are employees of Novartis.

BOSTON – Everolimus given with a reduced dose of tacrolimus to liver transplant patients yielded similar rates of acute rejection, graft loss, and death, but better kidney function than standard-dose tacrolimus alone at 2 years in a randomized, open-label, multicenter, controlled trial.

These 2-year results confirm and build on the recently published results of the trial at 1 year (Am. J. Transpl. 2012;12:3008-20), lead investigator Dr. Faouzi Saliba of Paul Brousse Hospital, Villejuif, France, reported at the annual meeting of the American Association for the Study of Liver Diseases.

Since the first study was published 9 years ago documenting a cumulative incidence of chronic renal failure of 28% after 10 years of tacrolimus treatment after liver transplant (N. Engl. J. Med. 2003;349:931-40), another study has reported estimated glomerular filtration rates (eGFRs) of less than 60 mL/min per 1.73 m² (stage 3 chronic kidney failure) for 58% of liver transplant recipients after 5 years of treatment with tacrolimus (Liver Transpl. 2009:15:1083-91).

On the basis of the effectiveness of everolimus in reducing the dose of calcineurin inhibitor needed for immunosuppression without reducing efficacy in patients with de novo kidney transplantation (Am. J. Transpl. 2010;10:1401-13), Dr. Saliba and his coinvestigators conducted the current trial.

Following a 30-day run-in period in which liver transplant recipients received tacrolimus with or without mycophenolate mofetil and prednisone, the investigators randomized 719 patients to three arms: two arms with everolimus 3-8 ng/mL, tacrolimus reduced to 3-5 ng/mL, and prednisone, and a control arm with tacrolimus dosed to a standard 8-12 ng/mL plus prednisone. After 4 months, in one of the reduced-dose arms, tacrolimus was withdrawn and the everolimus dose was increased to 8-10 ng/mL (231 patients), whereas the dose of everolimus was kept constant in the other reduced-dose arm (245 patients) and the dose of tacrolimus was kept the same in the control arm (243 patients). Prednisone could be eliminated at 4 months in any arm. However, enrollment into the tacrolimus withdrawal arm was stopped at the time of conversion to everolimus alone because of a high rate of rejection episodes, and the trial’s protocol was amended to compare efficacy between only the reduced-dose and control arms.

By 2 years, the number of patients who completed the study was similar in both the reduced-dose and control arms (82% vs. 84%, respectively), and similar percentages in each group remained on the study medications at 2 years (58% vs. 68%, respectively).

In each group, recipients were mostly men (74%) and white (80%-86%), with a mean age of 54 years and mean donor age of 49 years. They had a Model for End-Stage Liver Disease score of 19, and eGFRs of about 80 mL/min per 1.73 m².

Mean levels of tacrolimus dropped from 10.5 ng/mL at randomization to 4 ng/mL at 2 years in the dose-reduction arm, compared with 10 ng/mL to 7 ng/mL in the control arm.

At 2 years in the intent-to-treat population, the groups had similar rates of the composite primary end point of treated biopsy-proven acute rejection, graft failure, and death (10.5% in the dose-reduction arm and 12.5% in the control arm). Biopsy-proven acute rejection occurred at a significantly lower rate among dose-reduced patients (6%) than among control patients (13%). All of the episodes of acute rejection in the tacrolimus dose-reduced patients were borderline or mild based on the Banff rejection activity index. However, liver biopsies at 1 and 2 years were only part of the trial’s protocol for hepatitis C virus (HCV)-infected patients. The decision to biopsy was otherwise left up to the physicians of each center.

At 1 year, there appeared to be less fibrosis in patients who received everolimus, Dr. Saliba said in response to a question from the audience. In about half of the 75 HCV-infected patients in the dose-reduction arm, liver biopsies showed less fibrosis of at least stage 1 than in patients with HCV infection in the other group. The investigators are now analyzing 2-year data, he said.

The dose-reduced group maintained significantly better eGFR than the control group, through the duration of the trial, finishing with levels of 66 vs. 78 mL/min per 1.73 m².

Several types of adverse events with an incidence of at least 10% occurred more often in the dose-reduction arm than in the control arm, including leucopenia (13% vs. 5%), peripheral edema (20% vs. 13%), and hypercholesterolemia (11% vs. 4%).

Proteinuria of less than 0.5 g/24 hours occurred in 92%-93% of the patients; none of the patients had severe proteinuria of 3 g/24 hours or more.

One audience member noted that the most important patients to study in this clinical population are those on the borderline of renal failure with low eGFR and elevated creatinine, who would benefit most from improved renal function. Dr. Saliba said that at the time of randomization, the investigators looked at levels of eGFR in each group and over the course of the 2 years, more patients in the standard-dose tacrolimus arm had worsened renal function, whereas many in the dose-reduction arm had improved or at least stable renal function, and few had worsened function.

The study was sponsored by Novartis, which manufactures everolimus. Dr. Saliba reported financial ties to Novartis and Astellas Pharma (manufacturer of tacrolimus), as well as other companies that manufacture drugs used by liver transplant patients. Several other investigators reported financial ties to companies that manufacture antirejection drugs used in liver transplant patients, including Novartis. Three study investigators are employees of Novartis.

Survival rates remained high 1 year after implantation with the transcatheter aortic CoreValve in the postmarket ADVANCE study, initial results show.

At 1 year, overall survival was 82.1% and cardiovascular survival 88.2%. This compares with survival rates of 87.4% and 91.7% at 6 months and 95.5% and 96.6% at 30 days, principal investigator Dr. Axel Linke reported at Transcatheter Cardiovascular Therapeutics 2012.

"I think they’re outstanding," he said in an interview. "If you put it into the perspective of the PARTNER A and B cohorts [in the pivotal trial in the Sapien transcatheter valve system], our mortality rate is, in absolute values, 8 to 13% lower."

One explanation is that the 1,015-patient, postmarket ADVANCE study sought out centers experienced with transcatheter aortic valve implantation (TAVI). The 44 centers in Western Europe, Asia, and South America were required to have performed at least 40 TAVI procedures, with some German centers having done as many as 500, to be certified by a TAVI proctor and to have a heart team in place.

"Clearly, our centers were out of the learning curve," remarked Dr. Linke of the University of Leipzig (Germany) Heart Center.

By comparison, some centers in the PARTNER trial of the Edwards Lifesciences Sapien valve contributed just six or seven patients and were selected based on their experience with general cardiologic intervention, he observed.

The 1-year survival rates in ADVANCE also surpass those from early registries, notably the French Aortic National CoreValve and Edwards Registry, where the initial experience with TAVI was associated with interventional mistakes, which were linked to early mortality, Dr. Linke said.

The CoreValve System has been implanted in more than 30,000 patients since its approval in the European Union in 2007, but is limited to investigational use in the United States and Japan.

No details were presented regarding mortality in various subgroups or complications such as stroke, paravalvular leaks or left bundle branch block (LBBB). A recent analysis raised concerns about LBBB, showing that one-third of 202 consecutive patients with no prior conduction disturbances developed new-onset LBBB after TAVI with a balloon-expandable valve (Sapien or Sapien XT). Although it resolved in 37.7% by hospital discharge and 57.3% at 6- to 12-month follow-up, patients with persistent LBBB had a significantly higher incidence of syncope and complete atrioventricular block requiring a permanent pacemaker (J. Am. Coll. Cardiol. 2012;60:1743-52 [doi:10.1016/j.jacc.2012.035]).

Dr. Linke said they will look at LBBB in more detailed analyses expected from ADVANCE in the coming weeks, but that there’s been no evidence of a problem with LBBB in earlier follow-up in ADVANCE or from other CoreValve users.

"Survival curves are absolutely identical up to the 6-month follow-up, so there’s no reason to believe they should be worse afterwards, although I can’t be exactly sure right now," he said, adding that in the publication, survival curves from patients with and without new-onset LBBB "started to diverge very early."

Quality of life data from ADVANCE, reported in a separate poster session at the meeting, showed significant benefits with the CoreValve, even among higher-risk patients.

Scores on the European Quality of Life–5 Dimensions (EQ-5D), which ranges from 0 (death) to 1 (perfect health), improved from 0.62 at baseline to 0.72 at 1 month, where it remained at 6 months, both highly significant differences from baseline.

On the Short Form Health Survey–12 (SF-12), scores at baseline, 1 month, and 6 months were 32.8, 39, and 39.7 for the physical component and 46.2, 48.5, and 50 for the mental component.

"Basically, whatever is gained, is gained very early from the baseline to the 1-month follow-up in the majority of the cases," said Dr. Linke.

The 322 higher-risk patients entering the study with a logistic EuroSCORE of more than 20 had significantly worse baseline health-related quality of life than did those with a EuroSCORE of 10 or less, but experienced significant improvements after TAVI on the EQ-5D at 1 month and on both components of the SF-12 at 6 months, all significant changes.

The access route used during TAVI had no impact on quality of life improvement at 6 months.

Dr. Linke reported serving as an adviser or consultant for Medtronic, which sponsored the study.

Survival rates remained high 1 year after implantation with the transcatheter aortic CoreValve in the postmarket ADVANCE study, initial results show.

At 1 year, overall survival was 82.1% and cardiovascular survival 88.2%. This compares with survival rates of 87.4% and 91.7% at 6 months and 95.5% and 96.6% at 30 days, principal investigator Dr. Axel Linke reported at Transcatheter Cardiovascular Therapeutics 2012.

"I think they’re outstanding," he said in an interview. "If you put it into the perspective of the PARTNER A and B cohorts [in the pivotal trial in the Sapien transcatheter valve system], our mortality rate is, in absolute values, 8 to 13% lower."

One explanation is that the 1,015-patient, postmarket ADVANCE study sought out centers experienced with transcatheter aortic valve implantation (TAVI). The 44 centers in Western Europe, Asia, and South America were required to have performed at least 40 TAVI procedures, with some German centers having done as many as 500, to be certified by a TAVI proctor and to have a heart team in place.

"Clearly, our centers were out of the learning curve," remarked Dr. Linke of the University of Leipzig (Germany) Heart Center.

By comparison, some centers in the PARTNER trial of the Edwards Lifesciences Sapien valve contributed just six or seven patients and were selected based on their experience with general cardiologic intervention, he observed.

The 1-year survival rates in ADVANCE also surpass those from early registries, notably the French Aortic National CoreValve and Edwards Registry, where the initial experience with TAVI was associated with interventional mistakes, which were linked to early mortality, Dr. Linke said.

The CoreValve System has been implanted in more than 30,000 patients since its approval in the European Union in 2007, but is limited to investigational use in the United States and Japan.

No details were presented regarding mortality in various subgroups or complications such as stroke, paravalvular leaks or left bundle branch block (LBBB). A recent analysis raised concerns about LBBB, showing that one-third of 202 consecutive patients with no prior conduction disturbances developed new-onset LBBB after TAVI with a balloon-expandable valve (Sapien or Sapien XT). Although it resolved in 37.7% by hospital discharge and 57.3% at 6- to 12-month follow-up, patients with persistent LBBB had a significantly higher incidence of syncope and complete atrioventricular block requiring a permanent pacemaker (J. Am. Coll. Cardiol. 2012;60:1743-52 [doi:10.1016/j.jacc.2012.035]).

Dr. Linke said they will look at LBBB in more detailed analyses expected from ADVANCE in the coming weeks, but that there’s been no evidence of a problem with LBBB in earlier follow-up in ADVANCE or from other CoreValve users.

"Survival curves are absolutely identical up to the 6-month follow-up, so there’s no reason to believe they should be worse afterwards, although I can’t be exactly sure right now," he said, adding that in the publication, survival curves from patients with and without new-onset LBBB "started to diverge very early."

Quality of life data from ADVANCE, reported in a separate poster session at the meeting, showed significant benefits with the CoreValve, even among higher-risk patients.

Scores on the European Quality of Life–5 Dimensions (EQ-5D), which ranges from 0 (death) to 1 (perfect health), improved from 0.62 at baseline to 0.72 at 1 month, where it remained at 6 months, both highly significant differences from baseline.

On the Short Form Health Survey–12 (SF-12), scores at baseline, 1 month, and 6 months were 32.8, 39, and 39.7 for the physical component and 46.2, 48.5, and 50 for the mental component.

"Basically, whatever is gained, is gained very early from the baseline to the 1-month follow-up in the majority of the cases," said Dr. Linke.

The 322 higher-risk patients entering the study with a logistic EuroSCORE of more than 20 had significantly worse baseline health-related quality of life than did those with a EuroSCORE of 10 or less, but experienced significant improvements after TAVI on the EQ-5D at 1 month and on both components of the SF-12 at 6 months, all significant changes.

The access route used during TAVI had no impact on quality of life improvement at 6 months.

Dr. Linke reported serving as an adviser or consultant for Medtronic, which sponsored the study.

Survival rates remained high 1 year after implantation with the transcatheter aortic CoreValve in the postmarket ADVANCE study, initial results show.

At 1 year, overall survival was 82.1% and cardiovascular survival 88.2%. This compares with survival rates of 87.4% and 91.7% at 6 months and 95.5% and 96.6% at 30 days, principal investigator Dr. Axel Linke reported at Transcatheter Cardiovascular Therapeutics 2012.

"I think they’re outstanding," he said in an interview. "If you put it into the perspective of the PARTNER A and B cohorts [in the pivotal trial in the Sapien transcatheter valve system], our mortality rate is, in absolute values, 8 to 13% lower."

One explanation is that the 1,015-patient, postmarket ADVANCE study sought out centers experienced with transcatheter aortic valve implantation (TAVI). The 44 centers in Western Europe, Asia, and South America were required to have performed at least 40 TAVI procedures, with some German centers having done as many as 500, to be certified by a TAVI proctor and to have a heart team in place.

"Clearly, our centers were out of the learning curve," remarked Dr. Linke of the University of Leipzig (Germany) Heart Center.

By comparison, some centers in the PARTNER trial of the Edwards Lifesciences Sapien valve contributed just six or seven patients and were selected based on their experience with general cardiologic intervention, he observed.

The 1-year survival rates in ADVANCE also surpass those from early registries, notably the French Aortic National CoreValve and Edwards Registry, where the initial experience with TAVI was associated with interventional mistakes, which were linked to early mortality, Dr. Linke said.

The CoreValve System has been implanted in more than 30,000 patients since its approval in the European Union in 2007, but is limited to investigational use in the United States and Japan.

No details were presented regarding mortality in various subgroups or complications such as stroke, paravalvular leaks or left bundle branch block (LBBB). A recent analysis raised concerns about LBBB, showing that one-third of 202 consecutive patients with no prior conduction disturbances developed new-onset LBBB after TAVI with a balloon-expandable valve (Sapien or Sapien XT). Although it resolved in 37.7% by hospital discharge and 57.3% at 6- to 12-month follow-up, patients with persistent LBBB had a significantly higher incidence of syncope and complete atrioventricular block requiring a permanent pacemaker (J. Am. Coll. Cardiol. 2012;60:1743-52 [doi:10.1016/j.jacc.2012.035]).

Dr. Linke said they will look at LBBB in more detailed analyses expected from ADVANCE in the coming weeks, but that there’s been no evidence of a problem with LBBB in earlier follow-up in ADVANCE or from other CoreValve users.

"Survival curves are absolutely identical up to the 6-month follow-up, so there’s no reason to believe they should be worse afterwards, although I can’t be exactly sure right now," he said, adding that in the publication, survival curves from patients with and without new-onset LBBB "started to diverge very early."

Quality of life data from ADVANCE, reported in a separate poster session at the meeting, showed significant benefits with the CoreValve, even among higher-risk patients.

Scores on the European Quality of Life–5 Dimensions (EQ-5D), which ranges from 0 (death) to 1 (perfect health), improved from 0.62 at baseline to 0.72 at 1 month, where it remained at 6 months, both highly significant differences from baseline.

On the Short Form Health Survey–12 (SF-12), scores at baseline, 1 month, and 6 months were 32.8, 39, and 39.7 for the physical component and 46.2, 48.5, and 50 for the mental component.

"Basically, whatever is gained, is gained very early from the baseline to the 1-month follow-up in the majority of the cases," said Dr. Linke.

The 322 higher-risk patients entering the study with a logistic EuroSCORE of more than 20 had significantly worse baseline health-related quality of life than did those with a EuroSCORE of 10 or less, but experienced significant improvements after TAVI on the EQ-5D at 1 month and on both components of the SF-12 at 6 months, all significant changes.

The access route used during TAVI had no impact on quality of life improvement at 6 months.

Dr. Linke reported serving as an adviser or consultant for Medtronic, which sponsored the study.

BOSTON – Prior bariatric surgery appears to be an independent risk factor for acetaminophen-related acute liver failure or injury, investigators reported at the annual meeting of the American Association for the Study of Liver Diseases.

A retrospective study of patients with acute liver failure (ALF) showed that 9 of 54 (17%) patients with ALF attributed to acetaminophen (APAP-ALF) had previously had bariatric surgery, compared with none of 47 patients with ALF from other causes, said Dr. Edward W. Holt, a researcher at the California Pacific Medical Center in San Francisco.

Although previous studies have shown associations between bariatric surgery and between alcohol abuse and APAP-ALF, they found that there were no significant differences in rates of suicidal ideation, depression, or alcohol abuse between patients who underwent bariatric surgery and those who had not, suggesting that bariatric surgery itself was a risk factor, Dr. Holt said.

"We feel that the implications of these findings are important," he said. "If validated in a larger cohort, our novel finding may identify a new group of patients at higher risk for APAP-ALF. If validated, additional warnings for patients with prior bariatric surgery may be warranted, similar to those currently in place for patients who consume three or more alcoholic drinks daily."

Possible explanations for the association include higher peak serum concentrations of ethanol after a challenge in patients who have undergone bariatric surgery, as well as higher rates of suicidal behaviors among these patients, compared with controls.

The investigators retrospectively reviewed data from their center on a prospectively identified cohort of 101 patients with acute liver failure from acetaminophen and other causes, including drug-induced, infections, lymphoma, ischemia, and heatstroke. Of the 54 patients with APAP-ALF, 8 had undergone roux-en-Y gastric bypass, and one had a duodenal switch procedure, at a mean of nearly 6 years before diagnosis of ALF.

Among the patients in the APAP-ALF group, the prevalence of bariatric surgery was 25.3-fold higher than the estimated prevalence in the general population (16.7% vs. 0.5%; estimate based on published literature and national hospital discharge data).

The patients with APAP-ALF and ALF from other causes were similar in age, but there were more women (P = .02) and whites (P less than .0001) in the APAP-ALF group, and patients in this group had significantly fewer deaths (P less than .0006) and transplants (P less than .0001).

When the researchers looked at possible risk factors for ALF, they found that patients in the ALF/other group had significantly lower frequencies of depression (P less than .001), alcohol abuse (P = .01), and acetaminophen-containing combination analgesics (P less than .0001). But when they compared patients with or without bariatric surgery, there were no significant differences in any of the variables mentioned above.

Dr. Holt noted that the study was limited by its single-center design, inability to test proposed mechanisms for the increased risk seen in patients who had undergone bariatric surgery (such as changes in glutathione levels), and the inability to perform a logistic regression analysis, as none of the patients with non-APAP ALF had undergone surgery.

In the question-and-response portion following his presentation, Dr. Holt was asked whether liver biopsies had been performed to see if patients had background steatohepatitis or fibrosis that might account for the results, and whether body mass index data were available.

He noted that the patients came primarily from his institution’s wide referral base, and they therefore did not have all the demographic or clinical information about each patient that they would have liked.

The study was internally funded. Dr. Holt reported no relevant financial disclosures.

BOSTON – Prior bariatric surgery appears to be an independent risk factor for acetaminophen-related acute liver failure or injury, investigators reported at the annual meeting of the American Association for the Study of Liver Diseases.

A retrospective study of patients with acute liver failure (ALF) showed that 9 of 54 (17%) patients with ALF attributed to acetaminophen (APAP-ALF) had previously had bariatric surgery, compared with none of 47 patients with ALF from other causes, said Dr. Edward W. Holt, a researcher at the California Pacific Medical Center in San Francisco.

Although previous studies have shown associations between bariatric surgery and between alcohol abuse and APAP-ALF, they found that there were no significant differences in rates of suicidal ideation, depression, or alcohol abuse between patients who underwent bariatric surgery and those who had not, suggesting that bariatric surgery itself was a risk factor, Dr. Holt said.

"We feel that the implications of these findings are important," he said. "If validated in a larger cohort, our novel finding may identify a new group of patients at higher risk for APAP-ALF. If validated, additional warnings for patients with prior bariatric surgery may be warranted, similar to those currently in place for patients who consume three or more alcoholic drinks daily."

Possible explanations for the association include higher peak serum concentrations of ethanol after a challenge in patients who have undergone bariatric surgery, as well as higher rates of suicidal behaviors among these patients, compared with controls.

The investigators retrospectively reviewed data from their center on a prospectively identified cohort of 101 patients with acute liver failure from acetaminophen and other causes, including drug-induced, infections, lymphoma, ischemia, and heatstroke. Of the 54 patients with APAP-ALF, 8 had undergone roux-en-Y gastric bypass, and one had a duodenal switch procedure, at a mean of nearly 6 years before diagnosis of ALF.

Among the patients in the APAP-ALF group, the prevalence of bariatric surgery was 25.3-fold higher than the estimated prevalence in the general population (16.7% vs. 0.5%; estimate based on published literature and national hospital discharge data).

The patients with APAP-ALF and ALF from other causes were similar in age, but there were more women (P = .02) and whites (P less than .0001) in the APAP-ALF group, and patients in this group had significantly fewer deaths (P less than .0006) and transplants (P less than .0001).

When the researchers looked at possible risk factors for ALF, they found that patients in the ALF/other group had significantly lower frequencies of depression (P less than .001), alcohol abuse (P = .01), and acetaminophen-containing combination analgesics (P less than .0001). But when they compared patients with or without bariatric surgery, there were no significant differences in any of the variables mentioned above.

Dr. Holt noted that the study was limited by its single-center design, inability to test proposed mechanisms for the increased risk seen in patients who had undergone bariatric surgery (such as changes in glutathione levels), and the inability to perform a logistic regression analysis, as none of the patients with non-APAP ALF had undergone surgery.

In the question-and-response portion following his presentation, Dr. Holt was asked whether liver biopsies had been performed to see if patients had background steatohepatitis or fibrosis that might account for the results, and whether body mass index data were available.

He noted that the patients came primarily from his institution’s wide referral base, and they therefore did not have all the demographic or clinical information about each patient that they would have liked.

The study was internally funded. Dr. Holt reported no relevant financial disclosures.

BOSTON – Prior bariatric surgery appears to be an independent risk factor for acetaminophen-related acute liver failure or injury, investigators reported at the annual meeting of the American Association for the Study of Liver Diseases.

A retrospective study of patients with acute liver failure (ALF) showed that 9 of 54 (17%) patients with ALF attributed to acetaminophen (APAP-ALF) had previously had bariatric surgery, compared with none of 47 patients with ALF from other causes, said Dr. Edward W. Holt, a researcher at the California Pacific Medical Center in San Francisco.

Although previous studies have shown associations between bariatric surgery and between alcohol abuse and APAP-ALF, they found that there were no significant differences in rates of suicidal ideation, depression, or alcohol abuse between patients who underwent bariatric surgery and those who had not, suggesting that bariatric surgery itself was a risk factor, Dr. Holt said.

"We feel that the implications of these findings are important," he said. "If validated in a larger cohort, our novel finding may identify a new group of patients at higher risk for APAP-ALF. If validated, additional warnings for patients with prior bariatric surgery may be warranted, similar to those currently in place for patients who consume three or more alcoholic drinks daily."

Possible explanations for the association include higher peak serum concentrations of ethanol after a challenge in patients who have undergone bariatric surgery, as well as higher rates of suicidal behaviors among these patients, compared with controls.

The investigators retrospectively reviewed data from their center on a prospectively identified cohort of 101 patients with acute liver failure from acetaminophen and other causes, including drug-induced, infections, lymphoma, ischemia, and heatstroke. Of the 54 patients with APAP-ALF, 8 had undergone roux-en-Y gastric bypass, and one had a duodenal switch procedure, at a mean of nearly 6 years before diagnosis of ALF.

Among the patients in the APAP-ALF group, the prevalence of bariatric surgery was 25.3-fold higher than the estimated prevalence in the general population (16.7% vs. 0.5%; estimate based on published literature and national hospital discharge data).

The patients with APAP-ALF and ALF from other causes were similar in age, but there were more women (P = .02) and whites (P less than .0001) in the APAP-ALF group, and patients in this group had significantly fewer deaths (P less than .0006) and transplants (P less than .0001).

When the researchers looked at possible risk factors for ALF, they found that patients in the ALF/other group had significantly lower frequencies of depression (P less than .001), alcohol abuse (P = .01), and acetaminophen-containing combination analgesics (P less than .0001). But when they compared patients with or without bariatric surgery, there were no significant differences in any of the variables mentioned above.

Dr. Holt noted that the study was limited by its single-center design, inability to test proposed mechanisms for the increased risk seen in patients who had undergone bariatric surgery (such as changes in glutathione levels), and the inability to perform a logistic regression analysis, as none of the patients with non-APAP ALF had undergone surgery.

In the question-and-response portion following his presentation, Dr. Holt was asked whether liver biopsies had been performed to see if patients had background steatohepatitis or fibrosis that might account for the results, and whether body mass index data were available.

He noted that the patients came primarily from his institution’s wide referral base, and they therefore did not have all the demographic or clinical information about each patient that they would have liked.

The study was internally funded. Dr. Holt reported no relevant financial disclosures.

SAN DIEGO – Patients who have minor elevations in serum creatinine after noncardiac surgery may be more likely to require a longer postoperative hospital stay and face a twofold increased risk of dying during that stay, preliminary data from a German study have shown.

"This is a big problem, because minor kidney dysfunction may not be noticed postoperatively," Dr. Felix Kork said in an interview during a poster session at Kidney Week 2012 "About 2% of people in general have a small increase in serum creatinine. They are at a greater risk of dying and staying longer in the hospital. Therapeutic options are needed to prevent this minor kidney dysfunction perioperatively."

Dr. Kork of the department of anesthesiology and intensive care medicine at Charité Hospital in Berlin and his associates retrospectively studied the records of 27,616 patients who underwent noncardiac surgery at Charité between 2006 and 2012. The researchers evaluated perioperative renal function by serum creatinine level.

After doing a multivariate analysis that adjusted for age, comorbidities, renal function, high-risk surgery, and postoperative admission to the ICU, the researchers observed that minor elevations in serum creatinine (defined as a range from 0.25 to 0.50 mg/dL) were independently associated with a prolonged hospital length of stay (HR for early discharge, 0.81) and a twofold increased risk of death during the postoperative hospital stay (OR, 1.99) compared with patients without an increase in serum creatinine level. Both findings were statistically significant.

"While adjusting for covariates, we also found that having received radio contrast agent before surgery is independently associated with a greater risk of mortality and hospital length of stay, whether there was kidney dysfunction after the radio contrast agent or not," Dr. Kork added. "We’re still looking into that [association]. It could be that those patients were sicker."

He acknowledged that the study’s retrospective design is a limitation. Because of this "we can only show the association between the serum creatinine increase and the outcome," he said. "We are planning a prospective study right now." Dr. Kork explained that the current study has been submitted for publication in an undisclosed journal, which will contain more detail about these findings.

Dr. Kork said that he had no relevant financial conflicts to disclose.

SAN DIEGO – Patients who have minor elevations in serum creatinine after noncardiac surgery may be more likely to require a longer postoperative hospital stay and face a twofold increased risk of dying during that stay, preliminary data from a German study have shown.

"This is a big problem, because minor kidney dysfunction may not be noticed postoperatively," Dr. Felix Kork said in an interview during a poster session at Kidney Week 2012 "About 2% of people in general have a small increase in serum creatinine. They are at a greater risk of dying and staying longer in the hospital. Therapeutic options are needed to prevent this minor kidney dysfunction perioperatively."

Dr. Kork of the department of anesthesiology and intensive care medicine at Charité Hospital in Berlin and his associates retrospectively studied the records of 27,616 patients who underwent noncardiac surgery at Charité between 2006 and 2012. The researchers evaluated perioperative renal function by serum creatinine level.

After doing a multivariate analysis that adjusted for age, comorbidities, renal function, high-risk surgery, and postoperative admission to the ICU, the researchers observed that minor elevations in serum creatinine (defined as a range from 0.25 to 0.50 mg/dL) were independently associated with a prolonged hospital length of stay (HR for early discharge, 0.81) and a twofold increased risk of death during the postoperative hospital stay (OR, 1.99) compared with patients without an increase in serum creatinine level. Both findings were statistically significant.

"While adjusting for covariates, we also found that having received radio contrast agent before surgery is independently associated with a greater risk of mortality and hospital length of stay, whether there was kidney dysfunction after the radio contrast agent or not," Dr. Kork added. "We’re still looking into that [association]. It could be that those patients were sicker."

He acknowledged that the study’s retrospective design is a limitation. Because of this "we can only show the association between the serum creatinine increase and the outcome," he said. "We are planning a prospective study right now." Dr. Kork explained that the current study has been submitted for publication in an undisclosed journal, which will contain more detail about these findings.

Dr. Kork said that he had no relevant financial conflicts to disclose.

SAN DIEGO – Patients who have minor elevations in serum creatinine after noncardiac surgery may be more likely to require a longer postoperative hospital stay and face a twofold increased risk of dying during that stay, preliminary data from a German study have shown.

"This is a big problem, because minor kidney dysfunction may not be noticed postoperatively," Dr. Felix Kork said in an interview during a poster session at Kidney Week 2012 "About 2% of people in general have a small increase in serum creatinine. They are at a greater risk of dying and staying longer in the hospital. Therapeutic options are needed to prevent this minor kidney dysfunction perioperatively."

Dr. Kork of the department of anesthesiology and intensive care medicine at Charité Hospital in Berlin and his associates retrospectively studied the records of 27,616 patients who underwent noncardiac surgery at Charité between 2006 and 2012. The researchers evaluated perioperative renal function by serum creatinine level.

After doing a multivariate analysis that adjusted for age, comorbidities, renal function, high-risk surgery, and postoperative admission to the ICU, the researchers observed that minor elevations in serum creatinine (defined as a range from 0.25 to 0.50 mg/dL) were independently associated with a prolonged hospital length of stay (HR for early discharge, 0.81) and a twofold increased risk of death during the postoperative hospital stay (OR, 1.99) compared with patients without an increase in serum creatinine level. Both findings were statistically significant.

"While adjusting for covariates, we also found that having received radio contrast agent before surgery is independently associated with a greater risk of mortality and hospital length of stay, whether there was kidney dysfunction after the radio contrast agent or not," Dr. Kork added. "We’re still looking into that [association]. It could be that those patients were sicker."

He acknowledged that the study’s retrospective design is a limitation. Because of this "we can only show the association between the serum creatinine increase and the outcome," he said. "We are planning a prospective study right now." Dr. Kork explained that the current study has been submitted for publication in an undisclosed journal, which will contain more detail about these findings.

Dr. Kork said that he had no relevant financial conflicts to disclose.

Although unraveling the human genome has been exciting and potentially beneficial, I was a bit dismayed to discover that our genes barely outnumber those of the chimpanzee and, in fact, are only 50% greater in number than those of the fruit fly. If they were able to communicate, even the most discriminating chimpanzee – and especially the humble fruit fly – would likely admit that they are several rungs below us on the animal kingdom ladder. Fortunately, it turns out that this is not the whole story.

The human microbiome project (HMP), close on the heels of the genome undertaking, has found that we have many more genes working for us than those located on the strands of our DNA. The HMP analysis reveals that each of us has more than 100 trillion microorganisms living in the many nooks and crannies of our bodies, with the highest concentration in the gastrointestinal tract. This population of microbes is incredibly diverse, and its exact composition is unique to each of us. Thus, in addition to the individuality granted to us by the genes we receive from our parents, each of us is also a distinctive and rather complex ecosystem.

Not only do these creatures live in and on us peacefully most of the time, they also add to our genetic complement. Whereas our DNA contains only 23,000 genes, these microorganisms in aggregate account for 100 times more genes, several of which transcribe proteins that are essential for our normal daily functioning. For example, they manufacture enzymes that allow digestion of complex carbohydrates that account for more than 10% of our daily calories and that would be indigestible if it were not for the contributions of this microscopic workforce. They also make a variety of vitamins (for example, folic acid, B₂, and B₁₂), and they have the capability of gearing production to one’s needs depending on diet and other circumstances. Furthermore, the microbiome likely plays a significant role in the development of our immune system.

When this large population of indigenous bacteria is in appropriate balance, all is well. However, when the equilibrium among species is disrupted by antibiotic therapy or other environmental influences, one or more of a long list of maladies may result. Alterations in the microbiome have been implicated as being a factor in diseases as diverse as colon and pancreatic cancer, diabetes, autism, multiple sclerosis, irritable bowel syndrome, and Clostridium difficile colitis. The latter, usually caused by antibiotic therapy, has even been treated successfully by restoring the microbiome to its normal state by means of a stool transplant from a normal donor. The relationship between the composition of the microbiome and the other disorders is less well understood but is fertile ground for further studies. Such investigations may open doors to future therapies for heretofore untreatable diseases.

Particularly fascinating is the association between the microbiome and the nutritional state. Since microbiomes play an important role in processing what we eat, it makes sense that these microscopic travelers might in part determine our body habitus. Dr. Jeffrey Gordon and his associates at Washington University, St. Louis, have investigated this intriguing prospect (Nature 2006;44:1022-3). They have shown in both animal and human studies that the composition of the microbiome is closely related to the degree of obesity or leanness of the subjects. Of the 100 or so known phyla of bacteria, only two, Bacteroidetes and Firmicutes, account for more than 90% of the microbes in our gastrointestinal tract. Obese mice and humans have a higher ratio of firmicutes to bacteroidetes than do their lean counterparts. Moreover, transplanting the microbiome from obese mice to germ-free animals results in an increase in the body fat of the latter group. Additionally, obese individuals who effectively diet over time increase their intestinal Bacteroidetes-to-Firmicutes ratio.

A common topic of discussion in Surgery News is the worldwide epidemic of obesity and its treatment with a variety of surgical procedures. It is within the realm of possibility that simply altering the microbiome of obese patients might help to resolve this affliction, which impairs the quality of life of so many.

So what is the gift that keeps on giving? It is our microbiome. For more than a century, bacteria have been considered one of the scourges of mankind. It is appropriate as the holiday season approaches that we finally acknowledge the contributions that these usually despised organisms make to our daily welfare. In turn and in the spirit of giving back, we can take some pride in the fact that we provide a warm and hospitable home for these friendly symbionts.

Dr. Rikkers is editor in chief of Surgery News.

Although unraveling the human genome has been exciting and potentially beneficial, I was a bit dismayed to discover that our genes barely outnumber those of the chimpanzee and, in fact, are only 50% greater in number than those of the fruit fly. If they were able to communicate, even the most discriminating chimpanzee – and especially the humble fruit fly – would likely admit that they are several rungs below us on the animal kingdom ladder. Fortunately, it turns out that this is not the whole story.

The human microbiome project (HMP), close on the heels of the genome undertaking, has found that we have many more genes working for us than those located on the strands of our DNA. The HMP analysis reveals that each of us has more than 100 trillion microorganisms living in the many nooks and crannies of our bodies, with the highest concentration in the gastrointestinal tract. This population of microbes is incredibly diverse, and its exact composition is unique to each of us. Thus, in addition to the individuality granted to us by the genes we receive from our parents, each of us is also a distinctive and rather complex ecosystem.

Not only do these creatures live in and on us peacefully most of the time, they also add to our genetic complement. Whereas our DNA contains only 23,000 genes, these microorganisms in aggregate account for 100 times more genes, several of which transcribe proteins that are essential for our normal daily functioning. For example, they manufacture enzymes that allow digestion of complex carbohydrates that account for more than 10% of our daily calories and that would be indigestible if it were not for the contributions of this microscopic workforce. They also make a variety of vitamins (for example, folic acid, B₂, and B₁₂), and they have the capability of gearing production to one’s needs depending on diet and other circumstances. Furthermore, the microbiome likely plays a significant role in the development of our immune system.

When this large population of indigenous bacteria is in appropriate balance, all is well. However, when the equilibrium among species is disrupted by antibiotic therapy or other environmental influences, one or more of a long list of maladies may result. Alterations in the microbiome have been implicated as being a factor in diseases as diverse as colon and pancreatic cancer, diabetes, autism, multiple sclerosis, irritable bowel syndrome, and Clostridium difficile colitis. The latter, usually caused by antibiotic therapy, has even been treated successfully by restoring the microbiome to its normal state by means of a stool transplant from a normal donor. The relationship between the composition of the microbiome and the other disorders is less well understood but is fertile ground for further studies. Such investigations may open doors to future therapies for heretofore untreatable diseases.

Particularly fascinating is the association between the microbiome and the nutritional state. Since microbiomes play an important role in processing what we eat, it makes sense that these microscopic travelers might in part determine our body habitus. Dr. Jeffrey Gordon and his associates at Washington University, St. Louis, have investigated this intriguing prospect (Nature 2006;44:1022-3). They have shown in both animal and human studies that the composition of the microbiome is closely related to the degree of obesity or leanness of the subjects. Of the 100 or so known phyla of bacteria, only two, Bacteroidetes and Firmicutes, account for more than 90% of the microbes in our gastrointestinal tract. Obese mice and humans have a higher ratio of firmicutes to bacteroidetes than do their lean counterparts. Moreover, transplanting the microbiome from obese mice to germ-free animals results in an increase in the body fat of the latter group. Additionally, obese individuals who effectively diet over time increase their intestinal Bacteroidetes-to-Firmicutes ratio.

A common topic of discussion in Surgery News is the worldwide epidemic of obesity and its treatment with a variety of surgical procedures. It is within the realm of possibility that simply altering the microbiome of obese patients might help to resolve this affliction, which impairs the quality of life of so many.

So what is the gift that keeps on giving? It is our microbiome. For more than a century, bacteria have been considered one of the scourges of mankind. It is appropriate as the holiday season approaches that we finally acknowledge the contributions that these usually despised organisms make to our daily welfare. In turn and in the spirit of giving back, we can take some pride in the fact that we provide a warm and hospitable home for these friendly symbionts.

Dr. Rikkers is editor in chief of Surgery News.

Although unraveling the human genome has been exciting and potentially beneficial, I was a bit dismayed to discover that our genes barely outnumber those of the chimpanzee and, in fact, are only 50% greater in number than those of the fruit fly. If they were able to communicate, even the most discriminating chimpanzee – and especially the humble fruit fly – would likely admit that they are several rungs below us on the animal kingdom ladder. Fortunately, it turns out that this is not the whole story.

The human microbiome project (HMP), close on the heels of the genome undertaking, has found that we have many more genes working for us than those located on the strands of our DNA. The HMP analysis reveals that each of us has more than 100 trillion microorganisms living in the many nooks and crannies of our bodies, with the highest concentration in the gastrointestinal tract. This population of microbes is incredibly diverse, and its exact composition is unique to each of us. Thus, in addition to the individuality granted to us by the genes we receive from our parents, each of us is also a distinctive and rather complex ecosystem.

Not only do these creatures live in and on us peacefully most of the time, they also add to our genetic complement. Whereas our DNA contains only 23,000 genes, these microorganisms in aggregate account for 100 times more genes, several of which transcribe proteins that are essential for our normal daily functioning. For example, they manufacture enzymes that allow digestion of complex carbohydrates that account for more than 10% of our daily calories and that would be indigestible if it were not for the contributions of this microscopic workforce. They also make a variety of vitamins (for example, folic acid, B₂, and B₁₂), and they have the capability of gearing production to one’s needs depending on diet and other circumstances. Furthermore, the microbiome likely plays a significant role in the development of our immune system.

When this large population of indigenous bacteria is in appropriate balance, all is well. However, when the equilibrium among species is disrupted by antibiotic therapy or other environmental influences, one or more of a long list of maladies may result. Alterations in the microbiome have been implicated as being a factor in diseases as diverse as colon and pancreatic cancer, diabetes, autism, multiple sclerosis, irritable bowel syndrome, and Clostridium difficile colitis. The latter, usually caused by antibiotic therapy, has even been treated successfully by restoring the microbiome to its normal state by means of a stool transplant from a normal donor. The relationship between the composition of the microbiome and the other disorders is less well understood but is fertile ground for further studies. Such investigations may open doors to future therapies for heretofore untreatable diseases.

Particularly fascinating is the association between the microbiome and the nutritional state. Since microbiomes play an important role in processing what we eat, it makes sense that these microscopic travelers might in part determine our body habitus. Dr. Jeffrey Gordon and his associates at Washington University, St. Louis, have investigated this intriguing prospect (Nature 2006;44:1022-3). They have shown in both animal and human studies that the composition of the microbiome is closely related to the degree of obesity or leanness of the subjects. Of the 100 or so known phyla of bacteria, only two, Bacteroidetes and Firmicutes, account for more than 90% of the microbes in our gastrointestinal tract. Obese mice and humans have a higher ratio of firmicutes to bacteroidetes than do their lean counterparts. Moreover, transplanting the microbiome from obese mice to germ-free animals results in an increase in the body fat of the latter group. Additionally, obese individuals who effectively diet over time increase their intestinal Bacteroidetes-to-Firmicutes ratio.

A common topic of discussion in Surgery News is the worldwide epidemic of obesity and its treatment with a variety of surgical procedures. It is within the realm of possibility that simply altering the microbiome of obese patients might help to resolve this affliction, which impairs the quality of life of so many.

So what is the gift that keeps on giving? It is our microbiome. For more than a century, bacteria have been considered one of the scourges of mankind. It is appropriate as the holiday season approaches that we finally acknowledge the contributions that these usually despised organisms make to our daily welfare. In turn and in the spirit of giving back, we can take some pride in the fact that we provide a warm and hospitable home for these friendly symbionts.

Dr. Rikkers is editor in chief of Surgery News.

WASHINGTON – A daily dose of strontium ranelate was associated with a significant delay in joint space narrowing in adults with symptomatic primary knee osteoarthritis, based on data from the phase III Strontium Ranelate Knee Osteoarthritis Trial (SEKOIA).

Strontium renalate currently is not approved in the United States, but it is approved in more than 100 countries for treating osteoporosis, said Dr. Jean-Yves Reginster, who is head of the Center for Investigation in Bone and Articular Cartilage Metabolism at the University of Liège (Belgium).

Data from nonclinical studies have shown that strontium’s bone-building activity has a positive impact on cartilage as well, he noted at the annual meeting of the American College of Rheumatology.

To examine the effectiveness of strontium ranelate on the progression of knee osteoarthritis (OA), Dr. Reginster and his colleagues randomized 1,683 adults with symptomatic primary knee OA to 1 g of strontium ranelate per day (566 patients), 2 g/day (558 patients), or a placebo (559 patients). Complete data were available for 1,371 patients. The average age of the patients was 63 years, and 69% were women.

Overall, treatment with either dose of strontium was associated with a significant delay in the radiographic progression of knee OA, which was assessed by measuring the radiological joint space narrowing (JSN) of the medial tibiofemoral compartment of the knee joint.

After 1 year, joint space width decreased by 0.27 mm in the 2-g/day group, 0.23 mm in the 1-g/day group, and 0.37 mm in the placebo group. The differences between the 2-g/day and 1-g/day groups and the placebo group were 0.10 mm and 0.14 mm, respectively.

Significantly less radiological progression was noted in both strontium groups, compared with the placebo group. The percentage of patients with radiological progression (defined as joint space narrowing of at least 0.5 mm) was 26% in the 2-g/day group, 22% in the 1-g/day group, and 33% in the placebo group.

"The structural effect is translated clinically into a lower number of patients having a radiological progression over thresholds predictive of OA-related surgery," Dr. Reginster said. The findings suggest that strontium ranelate could reduce the need for knee surgery in OA patients, he added.

In addition, significantly more patients in the 2-g/day group exceeded the minimally perceptible clinical improvement (MCPI) threshold, compared with the placebo patients, on subscores of pain, stiffness, and physical function. The percentage of patients in the 1-g/day group above this threshold was not significantly higher than in the placebo group.

No significant differences in adverse events were observed among the three groups, and the incidence of serious adverse events was 17% in all groups.

The study findings also appeared online on Nov. 9 (Ann. Rheum. Dis. 2012 [doi:10.1136/annrheumdis-2012-202231]).

The study was sponsored by Servier. Dr. Reginster disclosed financial relationships with multiple companies, including Servier.

WASHINGTON – A daily dose of strontium ranelate was associated with a significant delay in joint space narrowing in adults with symptomatic primary knee osteoarthritis, based on data from the phase III Strontium Ranelate Knee Osteoarthritis Trial (SEKOIA).

Strontium renalate currently is not approved in the United States, but it is approved in more than 100 countries for treating osteoporosis, said Dr. Jean-Yves Reginster, who is head of the Center for Investigation in Bone and Articular Cartilage Metabolism at the University of Liège (Belgium).

Data from nonclinical studies have shown that strontium’s bone-building activity has a positive impact on cartilage as well, he noted at the annual meeting of the American College of Rheumatology.

To examine the effectiveness of strontium ranelate on the progression of knee osteoarthritis (OA), Dr. Reginster and his colleagues randomized 1,683 adults with symptomatic primary knee OA to 1 g of strontium ranelate per day (566 patients), 2 g/day (558 patients), or a placebo (559 patients). Complete data were available for 1,371 patients. The average age of the patients was 63 years, and 69% were women.

Overall, treatment with either dose of strontium was associated with a significant delay in the radiographic progression of knee OA, which was assessed by measuring the radiological joint space narrowing (JSN) of the medial tibiofemoral compartment of the knee joint.

After 1 year, joint space width decreased by 0.27 mm in the 2-g/day group, 0.23 mm in the 1-g/day group, and 0.37 mm in the placebo group. The differences between the 2-g/day and 1-g/day groups and the placebo group were 0.10 mm and 0.14 mm, respectively.

Significantly less radiological progression was noted in both strontium groups, compared with the placebo group. The percentage of patients with radiological progression (defined as joint space narrowing of at least 0.5 mm) was 26% in the 2-g/day group, 22% in the 1-g/day group, and 33% in the placebo group.

"The structural effect is translated clinically into a lower number of patients having a radiological progression over thresholds predictive of OA-related surgery," Dr. Reginster said. The findings suggest that strontium ranelate could reduce the need for knee surgery in OA patients, he added.

In addition, significantly more patients in the 2-g/day group exceeded the minimally perceptible clinical improvement (MCPI) threshold, compared with the placebo patients, on subscores of pain, stiffness, and physical function. The percentage of patients in the 1-g/day group above this threshold was not significantly higher than in the placebo group.

No significant differences in adverse events were observed among the three groups, and the incidence of serious adverse events was 17% in all groups.

The study findings also appeared online on Nov. 9 (Ann. Rheum. Dis. 2012 [doi:10.1136/annrheumdis-2012-202231]).

The study was sponsored by Servier. Dr. Reginster disclosed financial relationships with multiple companies, including Servier.

WASHINGTON – A daily dose of strontium ranelate was associated with a significant delay in joint space narrowing in adults with symptomatic primary knee osteoarthritis, based on data from the phase III Strontium Ranelate Knee Osteoarthritis Trial (SEKOIA).

Strontium renalate currently is not approved in the United States, but it is approved in more than 100 countries for treating osteoporosis, said Dr. Jean-Yves Reginster, who is head of the Center for Investigation in Bone and Articular Cartilage Metabolism at the University of Liège (Belgium).

Data from nonclinical studies have shown that strontium’s bone-building activity has a positive impact on cartilage as well, he noted at the annual meeting of the American College of Rheumatology.

To examine the effectiveness of strontium ranelate on the progression of knee osteoarthritis (OA), Dr. Reginster and his colleagues randomized 1,683 adults with symptomatic primary knee OA to 1 g of strontium ranelate per day (566 patients), 2 g/day (558 patients), or a placebo (559 patients). Complete data were available for 1,371 patients. The average age of the patients was 63 years, and 69% were women.

Overall, treatment with either dose of strontium was associated with a significant delay in the radiographic progression of knee OA, which was assessed by measuring the radiological joint space narrowing (JSN) of the medial tibiofemoral compartment of the knee joint.

After 1 year, joint space width decreased by 0.27 mm in the 2-g/day group, 0.23 mm in the 1-g/day group, and 0.37 mm in the placebo group. The differences between the 2-g/day and 1-g/day groups and the placebo group were 0.10 mm and 0.14 mm, respectively.

Significantly less radiological progression was noted in both strontium groups, compared with the placebo group. The percentage of patients with radiological progression (defined as joint space narrowing of at least 0.5 mm) was 26% in the 2-g/day group, 22% in the 1-g/day group, and 33% in the placebo group.

"The structural effect is translated clinically into a lower number of patients having a radiological progression over thresholds predictive of OA-related surgery," Dr. Reginster said. The findings suggest that strontium ranelate could reduce the need for knee surgery in OA patients, he added.

In addition, significantly more patients in the 2-g/day group exceeded the minimally perceptible clinical improvement (MCPI) threshold, compared with the placebo patients, on subscores of pain, stiffness, and physical function. The percentage of patients in the 1-g/day group above this threshold was not significantly higher than in the placebo group.

No significant differences in adverse events were observed among the three groups, and the incidence of serious adverse events was 17% in all groups.

The study findings also appeared online on Nov. 9 (Ann. Rheum. Dis. 2012 [doi:10.1136/annrheumdis-2012-202231]).

The study was sponsored by Servier. Dr. Reginster disclosed financial relationships with multiple companies, including Servier.