Mark S. Lesney

A greater percentage of diabetic foot ulcers achieved complete closure with negative pressure wound therapy than with advanced moist wound therapy in a randomized controlled study of more than 300 patients.

There were also significantly fewer secondary amputations seen in the group undergoing negative pressure therapy, Dr. Peter A. Blume and colleagues reported.

Diabetic foot ulcers lead to nonhealing chronic wounds that are difficult to treat and are a significant risk factor for nontraumatic amputation.

Several diabetic foot ulcer treatments have been reported. All of them require integration of multiple treatment modalities, with debridement being the foundation for these therapies. Success of any particular form of treatment is dependent on the appropriate match of patient and treatment factors, according to Dr. Blume of the North American Center for Limb Preservation, New Haven, Conn., and colleagues.

The study goal was to determine whether negative pressure wound therapy (NPWT) was a better or equivalent treatment to advanced moist wound therapy (AMWT) in concurrence with debridement for treating foot ulcers in diabetic adults with adequate blood circulation.

Patients were randomly assigned to either NPWT, which used vacuum-assisted closure, or AMWT, which primarily used hydrogels and alginates. The study could not be blinded because of the distinct nature of the two therapies, according to the study investigators.

The multicenter study enrolled 342 patients with a mean age of 58 years over the period of August 2002 to August 2005; 79% of the patients were men. All patients were initially debrided as needed within 2 days of randomization and received standard off-loading therapy as needed after treatment was initiated.

Treatment was continued until ulcer closure, sufficient granulation tissue formation for healing, or until day 112. All patients were examined weekly for the first 4 weeks then every other week until day 112 or ulcer closure. Patients achieving ulcer closure were followed at 3 and 9 months (Diabetes Care 2008;31:631–6).

Complete ulcer closure was defined as skin closure (100% reepithelialization) without a draining or dressing requirement. Closure occurred in 73 of 169 (43%) of the NPWT patients, compared with 48 of 166 (29%) of the AMWT patients. In addition, significantly more NPWT patients achieved 75% closure (105 of 169, 62%), than did AMWT patients (85 of 166, 51%).

The incidence of secondary amputations was also significantly less for NPWT (4%) than for AMWT (10%).

"Although the exact mechanism of the decrease in secondary amputations remains unclear, treatment of DFUs [diabetic foot ulcers] with NPWT appears to promote significant healing," the authors concluded.

Dr. John Lantis (Saint Luke's Roosevelt Hospital, New York), a study coauthor, disclosed receiving honoraria from KCI USA, which provided the vacuum therapy system used and whose global biometrics group provided the data analysis.

ELSEVIER GLOBAL MEDICAL NEWS

A greater percentage of diabetic foot ulcers achieved complete closure with negative pressure wound therapy than with advanced moist wound therapy in a randomized controlled study of more than 300 patients.

There were also significantly fewer secondary amputations seen in the group undergoing negative pressure therapy, Dr. Peter A. Blume and colleagues reported.

Diabetic foot ulcers lead to nonhealing chronic wounds that are difficult to treat and are a significant risk factor for nontraumatic amputation.

Several diabetic foot ulcer treatments have been reported. All of them require integration of multiple treatment modalities, with debridement being the foundation for these therapies. Success of any particular form of treatment is dependent on the appropriate match of patient and treatment factors, according to Dr. Blume of the North American Center for Limb Preservation, New Haven, Conn., and colleagues.

The study goal was to determine whether negative pressure wound therapy (NPWT) was a better or equivalent treatment to advanced moist wound therapy (AMWT) in concurrence with debridement for treating foot ulcers in diabetic adults with adequate blood circulation.

Patients were randomly assigned to either NPWT, which used vacuum-assisted closure, or AMWT, which primarily used hydrogels and alginates. The study could not be blinded because of the distinct nature of the two therapies, according to the study investigators.

The multicenter study enrolled 342 patients with a mean age of 58 years over the period of August 2002 to August 2005; 79% of the patients were men. All patients were initially debrided as needed within 2 days of randomization and received standard off-loading therapy as needed after treatment was initiated.

Treatment was continued until ulcer closure, sufficient granulation tissue formation for healing, or until day 112. All patients were examined weekly for the first 4 weeks then every other week until day 112 or ulcer closure. Patients achieving ulcer closure were followed at 3 and 9 months (Diabetes Care 2008;31:631–6).

Complete ulcer closure was defined as skin closure (100% reepithelialization) without a draining or dressing requirement. Closure occurred in 73 of 169 (43%) of the NPWT patients, compared with 48 of 166 (29%) of the AMWT patients. In addition, significantly more NPWT patients achieved 75% closure (105 of 169, 62%), than did AMWT patients (85 of 166, 51%).

The incidence of secondary amputations was also significantly less for NPWT (4%) than for AMWT (10%).

"Although the exact mechanism of the decrease in secondary amputations remains unclear, treatment of DFUs [diabetic foot ulcers] with NPWT appears to promote significant healing," the authors concluded.

Dr. John Lantis (Saint Luke's Roosevelt Hospital, New York), a study coauthor, disclosed receiving honoraria from KCI USA, which provided the vacuum therapy system used and whose global biometrics group provided the data analysis.

ELSEVIER GLOBAL MEDICAL NEWS

A greater percentage of diabetic foot ulcers achieved complete closure with negative pressure wound therapy than with advanced moist wound therapy in a randomized controlled study of more than 300 patients.

There were also significantly fewer secondary amputations seen in the group undergoing negative pressure therapy, Dr. Peter A. Blume and colleagues reported.

Diabetic foot ulcers lead to nonhealing chronic wounds that are difficult to treat and are a significant risk factor for nontraumatic amputation.

Several diabetic foot ulcer treatments have been reported. All of them require integration of multiple treatment modalities, with debridement being the foundation for these therapies. Success of any particular form of treatment is dependent on the appropriate match of patient and treatment factors, according to Dr. Blume of the North American Center for Limb Preservation, New Haven, Conn., and colleagues.

The study goal was to determine whether negative pressure wound therapy (NPWT) was a better or equivalent treatment to advanced moist wound therapy (AMWT) in concurrence with debridement for treating foot ulcers in diabetic adults with adequate blood circulation.

Patients were randomly assigned to either NPWT, which used vacuum-assisted closure, or AMWT, which primarily used hydrogels and alginates. The study could not be blinded because of the distinct nature of the two therapies, according to the study investigators.

The multicenter study enrolled 342 patients with a mean age of 58 years over the period of August 2002 to August 2005; 79% of the patients were men. All patients were initially debrided as needed within 2 days of randomization and received standard off-loading therapy as needed after treatment was initiated.

Treatment was continued until ulcer closure, sufficient granulation tissue formation for healing, or until day 112. All patients were examined weekly for the first 4 weeks then every other week until day 112 or ulcer closure. Patients achieving ulcer closure were followed at 3 and 9 months (Diabetes Care 2008;31:631–6).

Complete ulcer closure was defined as skin closure (100% reepithelialization) without a draining or dressing requirement. Closure occurred in 73 of 169 (43%) of the NPWT patients, compared with 48 of 166 (29%) of the AMWT patients. In addition, significantly more NPWT patients achieved 75% closure (105 of 169, 62%), than did AMWT patients (85 of 166, 51%).

The incidence of secondary amputations was also significantly less for NPWT (4%) than for AMWT (10%).

"Although the exact mechanism of the decrease in secondary amputations remains unclear, treatment of DFUs [diabetic foot ulcers] with NPWT appears to promote significant healing," the authors concluded.

Dr. John Lantis (Saint Luke's Roosevelt Hospital, New York), a study coauthor, disclosed receiving honoraria from KCI USA, which provided the vacuum therapy system used and whose global biometrics group provided the data analysis.

ELSEVIER GLOBAL MEDICAL NEWS

Clinically significant macular edema with or without diabetic retinopathy correlates significantly with ischemic heart disease mortality in individuals with later-onset, but not earlier-onset diabetes mellitus, according to a large population study.

The researchers analyzed data on 954 younger-onset patients with diabetes and 1,295 older-onset patients, all of whom were participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), an ongoing prospective population-based cohort study initiated from August 1980 through July 1982. Younger onset was defined as diabetes diagnosed at under age 30 years (generally indicative of type 1 diabetes); the older onset group comprised those diagnosed at age 30 years and above (generally indicative of type 2 diabetes).

Clinically significant macular edema (CSME) was defined according to the Early Treatment of Diabetic Retinopathy classification protocol as the presence of retinal thickening at or within 500 mcm of the center of the macula or hard exudates at or within 500 mcm of the center of the macula, if associated with other characteristics of the disease, according to Dr. Flavio E. Hirai and his colleagues from the University of Wisconsin, Madison, and the Federal University of São Paulo, Brazil.

At baseline, CSME was 5.9% and 7.5% for the younger- and older-onset groups, respectively. After 20 years, 276 (about 29%) of individuals in the younger-onset group had died, 118 of ischemic heart disease and 18 of stroke. CSME status was not found to be associated with all-cause, ischemic heart disease, or stroke mortality. After 20 years, 1,123 (about 87%) of the older-onset group had died, with ischemic heart disease listed as a cause of death for 518 individuals, stroke for 193 individuals. CSME at baseline was significantly associated with increasing all-cause mortality in this group, adjusting for age, gender, and other risk factors (hazard ratio 1.27; 95% confidence interval). CSME was also significantly associated with ischemic heart disease in the age-gender-adjusted model (HR 1.56; 95% CI), but not with stroke mortality.

No correlations were seen between CSME and other factors such as age, diabetes duration, body mass index, nephropathy, or glycosylated hemoglobin status. However, in the older-onset group, there was a significantly higher association of ischemic heart disease mortality with CSME at baseline in those patients taking insulin (HR 1.58; 95% CI).

Diabetic retinopathy (DR) was also significantly associated with a higher risk of all-cause- and ischemic heart-disease mortality in individuals with DR alone or DR plus CSME.

“Although individuals who had CSME and DR had a 65% higher hazard of dying of ischemic heart disease compared with a 35% higher hazard among those with DR but without CSME at baseline, these differences were not statistically significant,” according to the authors (Am. J. Ophthalmol. 2008;145:700–6).

“Breakdown of the blood-retinal barrier, secondary to poor glycemic and blood pressure control, may be a risk indicator of similar microvascular disease in the heart and elsewhere,” the authors summarized.

The study was supported by a grant from the National Eye Institute; the authors indicated that they had no financial conflicts of interest.

ELSEVIER GLOBAL MEDICAL NEWS

Clinically significant macular edema with or without diabetic retinopathy correlates significantly with ischemic heart disease mortality in individuals with later-onset, but not earlier-onset diabetes mellitus, according to a large population study.

The researchers analyzed data on 954 younger-onset patients with diabetes and 1,295 older-onset patients, all of whom were participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), an ongoing prospective population-based cohort study initiated from August 1980 through July 1982. Younger onset was defined as diabetes diagnosed at under age 30 years (generally indicative of type 1 diabetes); the older onset group comprised those diagnosed at age 30 years and above (generally indicative of type 2 diabetes).

Clinically significant macular edema (CSME) was defined according to the Early Treatment of Diabetic Retinopathy classification protocol as the presence of retinal thickening at or within 500 mcm of the center of the macula or hard exudates at or within 500 mcm of the center of the macula, if associated with other characteristics of the disease, according to Dr. Flavio E. Hirai and his colleagues from the University of Wisconsin, Madison, and the Federal University of São Paulo, Brazil.

At baseline, CSME was 5.9% and 7.5% for the younger- and older-onset groups, respectively. After 20 years, 276 (about 29%) of individuals in the younger-onset group had died, 118 of ischemic heart disease and 18 of stroke. CSME status was not found to be associated with all-cause, ischemic heart disease, or stroke mortality. After 20 years, 1,123 (about 87%) of the older-onset group had died, with ischemic heart disease listed as a cause of death for 518 individuals, stroke for 193 individuals. CSME at baseline was significantly associated with increasing all-cause mortality in this group, adjusting for age, gender, and other risk factors (hazard ratio 1.27; 95% confidence interval). CSME was also significantly associated with ischemic heart disease in the age-gender-adjusted model (HR 1.56; 95% CI), but not with stroke mortality.

No correlations were seen between CSME and other factors such as age, diabetes duration, body mass index, nephropathy, or glycosylated hemoglobin status. However, in the older-onset group, there was a significantly higher association of ischemic heart disease mortality with CSME at baseline in those patients taking insulin (HR 1.58; 95% CI).

Diabetic retinopathy (DR) was also significantly associated with a higher risk of all-cause- and ischemic heart-disease mortality in individuals with DR alone or DR plus CSME.

“Although individuals who had CSME and DR had a 65% higher hazard of dying of ischemic heart disease compared with a 35% higher hazard among those with DR but without CSME at baseline, these differences were not statistically significant,” according to the authors (Am. J. Ophthalmol. 2008;145:700–6).

“Breakdown of the blood-retinal barrier, secondary to poor glycemic and blood pressure control, may be a risk indicator of similar microvascular disease in the heart and elsewhere,” the authors summarized.

The study was supported by a grant from the National Eye Institute; the authors indicated that they had no financial conflicts of interest.

ELSEVIER GLOBAL MEDICAL NEWS

Clinically significant macular edema with or without diabetic retinopathy correlates significantly with ischemic heart disease mortality in individuals with later-onset, but not earlier-onset diabetes mellitus, according to a large population study.

The researchers analyzed data on 954 younger-onset patients with diabetes and 1,295 older-onset patients, all of whom were participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), an ongoing prospective population-based cohort study initiated from August 1980 through July 1982. Younger onset was defined as diabetes diagnosed at under age 30 years (generally indicative of type 1 diabetes); the older onset group comprised those diagnosed at age 30 years and above (generally indicative of type 2 diabetes).

Clinically significant macular edema (CSME) was defined according to the Early Treatment of Diabetic Retinopathy classification protocol as the presence of retinal thickening at or within 500 mcm of the center of the macula or hard exudates at or within 500 mcm of the center of the macula, if associated with other characteristics of the disease, according to Dr. Flavio E. Hirai and his colleagues from the University of Wisconsin, Madison, and the Federal University of São Paulo, Brazil.

At baseline, CSME was 5.9% and 7.5% for the younger- and older-onset groups, respectively. After 20 years, 276 (about 29%) of individuals in the younger-onset group had died, 118 of ischemic heart disease and 18 of stroke. CSME status was not found to be associated with all-cause, ischemic heart disease, or stroke mortality. After 20 years, 1,123 (about 87%) of the older-onset group had died, with ischemic heart disease listed as a cause of death for 518 individuals, stroke for 193 individuals. CSME at baseline was significantly associated with increasing all-cause mortality in this group, adjusting for age, gender, and other risk factors (hazard ratio 1.27; 95% confidence interval). CSME was also significantly associated with ischemic heart disease in the age-gender-adjusted model (HR 1.56; 95% CI), but not with stroke mortality.

No correlations were seen between CSME and other factors such as age, diabetes duration, body mass index, nephropathy, or glycosylated hemoglobin status. However, in the older-onset group, there was a significantly higher association of ischemic heart disease mortality with CSME at baseline in those patients taking insulin (HR 1.58; 95% CI).

Diabetic retinopathy (DR) was also significantly associated with a higher risk of all-cause- and ischemic heart-disease mortality in individuals with DR alone or DR plus CSME.

“Although individuals who had CSME and DR had a 65% higher hazard of dying of ischemic heart disease compared with a 35% higher hazard among those with DR but without CSME at baseline, these differences were not statistically significant,” according to the authors (Am. J. Ophthalmol. 2008;145:700–6).

“Breakdown of the blood-retinal barrier, secondary to poor glycemic and blood pressure control, may be a risk indicator of similar microvascular disease in the heart and elsewhere,” the authors summarized.

The study was supported by a grant from the National Eye Institute; the authors indicated that they had no financial conflicts of interest.

ELSEVIER GLOBAL MEDICAL NEWS

Deliberate error-seeding experiments involving a large congenital heart surgery database showed that even small levels of miscoding can substantially change mortality estimates. This was especially true for miscoding of procedure type and for operations with mortality below 10%.

Such error-driven variations in mortality estimates are especially troubling in an era when registry databases are more and more expected to form the foundation of risk analysis for various operations, and might even be used to evaluate the doctors and the institutions that perform these operations. In addition, errors in databases are not uncommon. One recent study of a carefully audited California database reported at least one diagnostically relevant error in 63% of patient records, according to Dr. Steve Gallivan and his colleagues.

Computer simulation techniques were used to create realistic analysis scenarios based on data from the Toronto Cardiovascular Surgery Database for Congenital Heart Surgery, which contains information on nearly 18,000 operations. This includes outcomes for 132 operation types from which 30 marker operations were chosen, each of which had been reported at least 100 times in the database and had nonzero mortality.

Four thought experiments were performed using the data on the marker operations. In the first experiment, the only errors introduced were random miscoding of outcomes with three scenarios: error rates of 1%, 3%, and 5%. Each of these scenarios showed considerable changes in mortality rates, especially when the true mortality rate was small (Eur. J. Cardiothorac. Surg. 2008;33:334–40).

In the second experiment, the only errors introduced comprised random omission of data at rates of 0%, 10%, or 20%, with the miscoding of outcomes fixed at 1%; these scenarios showed that random omission of data had no discernible effect on inaccuracies in mortality rate estimates. This was predicted by mathematical modeling.

In the third thought experiment, errors introduced comprised random outcome miscoding at different rates for deaths and survivors. A progressive increase in estimation error was seen when mortality rates fell, “and the scale of such overestimation is alarming for mortality rates below 10%,” according to Dr. Gallivan of University College, London, and his international colleagues.

The final thought experiment regarded introduced errors from miscoding of the operation type with no data omission or outcome miscoding. Three operations illustrated the potential dangers of such errors: ASD/secundum repair (recorded mortality rate 0.2%), TGA repair/arterial switch (mortality rate 9.0%), and the Norwood operation (mortality rate 36.3%). The assumption was made that each operation had an equal probability of being miscoded as one of the other two. As predicted from mathematical modeling, as the miscoding rate increased, the gross mortality rate for ASD/secundum repair became increasingly overestimated, the rate for TGA repair remained relatively the same, and the rate for Norwoods became increasingly underestimated, according to the authors.

“The results reported here sound a loud note of caution and perhaps it is time for a reappraisal of the clinical database structure. … There is often a somewhat misplaced belief that if one gathers a lot of data, then, if analyzed cleverly enough, they will reveal a new truth. … This view is wrongheaded; the reality is that the more data items that are collected, the more errors occur,” the authors stated. “The results we describe are alarming. Even moderate levels of error can lead to substantial inaccuracy in estimates of mortality rates and in some circumstances these inaccuracies can be gross, especially at the low mortality rates that are now prevalent in cardiothoracic surgery,” they added. “Even with … labor intensive methods, it is unlikely that errors will be completely eradicated. In view of this it is perhaps wise to adopt a more skeptical attitude to quantitative results, especially in relation to rates that are small.”

“Any data collection which is not verified in a professional way is not valid and can be misused and can be used against our profession. That's why I think that verification of data at the various levels, including the local institutional level, including the automatic and computerized level, up to visiting the sites and checking 100% of the data, is of the greatest importance,” said Dr. B. Maruszewski, one of the physicians responsible for the European Association for Cardio-Thoracic Surgery Congenital Database, in comments delivered at the paper's original presentation at the 2007 annual meeting of the European Association for Cardio-Thoracic Surgery.

As part of that discussion, Dr. Jaroslav Stark, one of the paper's authors, added, “You should collect as few data as possible, but even if your data set is only 20–25 items, it is still very important to check, because, as we have shown, a small error of 1% can increase your mortality estimates by five times.”

Deliberate error-seeding experiments involving a large congenital heart surgery database showed that even small levels of miscoding can substantially change mortality estimates. This was especially true for miscoding of procedure type and for operations with mortality below 10%.

Such error-driven variations in mortality estimates are especially troubling in an era when registry databases are more and more expected to form the foundation of risk analysis for various operations, and might even be used to evaluate the doctors and the institutions that perform these operations. In addition, errors in databases are not uncommon. One recent study of a carefully audited California database reported at least one diagnostically relevant error in 63% of patient records, according to Dr. Steve Gallivan and his colleagues.

Computer simulation techniques were used to create realistic analysis scenarios based on data from the Toronto Cardiovascular Surgery Database for Congenital Heart Surgery, which contains information on nearly 18,000 operations. This includes outcomes for 132 operation types from which 30 marker operations were chosen, each of which had been reported at least 100 times in the database and had nonzero mortality.

Four thought experiments were performed using the data on the marker operations. In the first experiment, the only errors introduced were random miscoding of outcomes with three scenarios: error rates of 1%, 3%, and 5%. Each of these scenarios showed considerable changes in mortality rates, especially when the true mortality rate was small (Eur. J. Cardiothorac. Surg. 2008;33:334–40).

In the second experiment, the only errors introduced comprised random omission of data at rates of 0%, 10%, or 20%, with the miscoding of outcomes fixed at 1%; these scenarios showed that random omission of data had no discernible effect on inaccuracies in mortality rate estimates. This was predicted by mathematical modeling.

In the third thought experiment, errors introduced comprised random outcome miscoding at different rates for deaths and survivors. A progressive increase in estimation error was seen when mortality rates fell, “and the scale of such overestimation is alarming for mortality rates below 10%,” according to Dr. Gallivan of University College, London, and his international colleagues.

The final thought experiment regarded introduced errors from miscoding of the operation type with no data omission or outcome miscoding. Three operations illustrated the potential dangers of such errors: ASD/secundum repair (recorded mortality rate 0.2%), TGA repair/arterial switch (mortality rate 9.0%), and the Norwood operation (mortality rate 36.3%). The assumption was made that each operation had an equal probability of being miscoded as one of the other two. As predicted from mathematical modeling, as the miscoding rate increased, the gross mortality rate for ASD/secundum repair became increasingly overestimated, the rate for TGA repair remained relatively the same, and the rate for Norwoods became increasingly underestimated, according to the authors.

“The results reported here sound a loud note of caution and perhaps it is time for a reappraisal of the clinical database structure. … There is often a somewhat misplaced belief that if one gathers a lot of data, then, if analyzed cleverly enough, they will reveal a new truth. … This view is wrongheaded; the reality is that the more data items that are collected, the more errors occur,” the authors stated. “The results we describe are alarming. Even moderate levels of error can lead to substantial inaccuracy in estimates of mortality rates and in some circumstances these inaccuracies can be gross, especially at the low mortality rates that are now prevalent in cardiothoracic surgery,” they added. “Even with … labor intensive methods, it is unlikely that errors will be completely eradicated. In view of this it is perhaps wise to adopt a more skeptical attitude to quantitative results, especially in relation to rates that are small.”

“Any data collection which is not verified in a professional way is not valid and can be misused and can be used against our profession. That's why I think that verification of data at the various levels, including the local institutional level, including the automatic and computerized level, up to visiting the sites and checking 100% of the data, is of the greatest importance,” said Dr. B. Maruszewski, one of the physicians responsible for the European Association for Cardio-Thoracic Surgery Congenital Database, in comments delivered at the paper's original presentation at the 2007 annual meeting of the European Association for Cardio-Thoracic Surgery.

As part of that discussion, Dr. Jaroslav Stark, one of the paper's authors, added, “You should collect as few data as possible, but even if your data set is only 20–25 items, it is still very important to check, because, as we have shown, a small error of 1% can increase your mortality estimates by five times.”

Deliberate error-seeding experiments involving a large congenital heart surgery database showed that even small levels of miscoding can substantially change mortality estimates. This was especially true for miscoding of procedure type and for operations with mortality below 10%.

Such error-driven variations in mortality estimates are especially troubling in an era when registry databases are more and more expected to form the foundation of risk analysis for various operations, and might even be used to evaluate the doctors and the institutions that perform these operations. In addition, errors in databases are not uncommon. One recent study of a carefully audited California database reported at least one diagnostically relevant error in 63% of patient records, according to Dr. Steve Gallivan and his colleagues.

Computer simulation techniques were used to create realistic analysis scenarios based on data from the Toronto Cardiovascular Surgery Database for Congenital Heart Surgery, which contains information on nearly 18,000 operations. This includes outcomes for 132 operation types from which 30 marker operations were chosen, each of which had been reported at least 100 times in the database and had nonzero mortality.

Four thought experiments were performed using the data on the marker operations. In the first experiment, the only errors introduced were random miscoding of outcomes with three scenarios: error rates of 1%, 3%, and 5%. Each of these scenarios showed considerable changes in mortality rates, especially when the true mortality rate was small (Eur. J. Cardiothorac. Surg. 2008;33:334–40).

In the second experiment, the only errors introduced comprised random omission of data at rates of 0%, 10%, or 20%, with the miscoding of outcomes fixed at 1%; these scenarios showed that random omission of data had no discernible effect on inaccuracies in mortality rate estimates. This was predicted by mathematical modeling.

In the third thought experiment, errors introduced comprised random outcome miscoding at different rates for deaths and survivors. A progressive increase in estimation error was seen when mortality rates fell, “and the scale of such overestimation is alarming for mortality rates below 10%,” according to Dr. Gallivan of University College, London, and his international colleagues.

The final thought experiment regarded introduced errors from miscoding of the operation type with no data omission or outcome miscoding. Three operations illustrated the potential dangers of such errors: ASD/secundum repair (recorded mortality rate 0.2%), TGA repair/arterial switch (mortality rate 9.0%), and the Norwood operation (mortality rate 36.3%). The assumption was made that each operation had an equal probability of being miscoded as one of the other two. As predicted from mathematical modeling, as the miscoding rate increased, the gross mortality rate for ASD/secundum repair became increasingly overestimated, the rate for TGA repair remained relatively the same, and the rate for Norwoods became increasingly underestimated, according to the authors.

“The results reported here sound a loud note of caution and perhaps it is time for a reappraisal of the clinical database structure. … There is often a somewhat misplaced belief that if one gathers a lot of data, then, if analyzed cleverly enough, they will reveal a new truth. … This view is wrongheaded; the reality is that the more data items that are collected, the more errors occur,” the authors stated. “The results we describe are alarming. Even moderate levels of error can lead to substantial inaccuracy in estimates of mortality rates and in some circumstances these inaccuracies can be gross, especially at the low mortality rates that are now prevalent in cardiothoracic surgery,” they added. “Even with … labor intensive methods, it is unlikely that errors will be completely eradicated. In view of this it is perhaps wise to adopt a more skeptical attitude to quantitative results, especially in relation to rates that are small.”

“Any data collection which is not verified in a professional way is not valid and can be misused and can be used against our profession. That's why I think that verification of data at the various levels, including the local institutional level, including the automatic and computerized level, up to visiting the sites and checking 100% of the data, is of the greatest importance,” said Dr. B. Maruszewski, one of the physicians responsible for the European Association for Cardio-Thoracic Surgery Congenital Database, in comments delivered at the paper's original presentation at the 2007 annual meeting of the European Association for Cardio-Thoracic Surgery.

As part of that discussion, Dr. Jaroslav Stark, one of the paper's authors, added, “You should collect as few data as possible, but even if your data set is only 20–25 items, it is still very important to check, because, as we have shown, a small error of 1% can increase your mortality estimates by five times.”

WASHINGTON — The vascular surgeon insists that revascularization was a success—and there are outcome images to prove it—but the diabetic foot becomes ischemic anyway, and the wound fails to heal.

This is an all too common scenario for physicians who care for these at-risk limbs and problem wounds. Such failures can be explained in a push-pull model of perfusion in these patients, and this model may well indicate what needs to be done for effective treatment, according to Dr. William J. Ennis.

The push-pull model essentially states that despite the "push" of restored macrocirculation from revascularization, the patient still needs the ability to "pull" blood nutrients into all parts of the limb via a functional microcirculation, said Dr. Ennis of the St. James Center for Comprehensive Wound & Disease Management in Chicago. He spoke at a meeting sponsored by George Washington University Hospital.

But creating "pull" is not an easy task, especially for patients with diabetes. In such individuals, a functional microcirculation may be a problem in its own right because of both physical and physiologic changes in their microvascular system brought on by the long-term chronic disease. In patients with poor microcirculation, successful revascularization of the larger vessels can lead to ischemic reperfusion injury in the tissues that they service. White cells stick and create reactive oxygen species that make it almost impossible for wounds to heal.

Damage models in diabetic foot wound responses after revascularization can borrow from cardiology, according to Dr. Ennis—concepts such as tissue "stunning," whereby tissue is traumatized by the reperfusion injury without being killed and remains capable of recuperating; no reflow, such as that caused by a mechanical obstruction from thrombus; or functional alterations, such as the endothelial dysfunction that is known to occur in diabetics.

It is critical to restore a microvascular "pull" as soon as possible in order for the wound to heal and, in many cases, in order for the limb to survive, according to Dr. Ennis. "It is almost silly for us to think that we can solve the entire process with a simple bypass. We may end up with a mixed pattern, persistent ischemia, and something known as no reflow. These are the patients who get bypass and nothing happens—the wound continues or the open-air site never heals…. It is so frustrating for us as wound clinicians to see a great bypass and still lose a limb. It's not uncommon, and this [microcirculatory problem] is why."

Angiogenesis agents are one option for restoring microcirculatory "pull." One such treatment may be ultrasound. Pulsatile flow in tissue pushes and pulls on the endothelium and causes nitric oxide release. Ultrasound can be used to "fake the tissue out that it is receiving pulsatile flow," according to Dr. Ennis, who along with his colleagues has studied the use of ultrasound to induce angiogenesis, pulsatile flow, and ultimately wound healing.

"We were able to show that there was a difference in angiogenesis at approximately 41/2 weeks with ultrasound therapy. … This was one of the first times we were actually able to quantify the angiogenesis response and correlate it to wound healing," he explained (Advances in Skin & Wound Care 2006;19:437–46).

The future may include novel treatments for reperfusion injury and ischemia such as bone marrow stem cell therapy, which may be available in 5–10 years, and growth factor molecules, many of which are currently being tested in phase I trials, according to Dr. Ennis.

Regardless of which treatment is chosen, it is also important for the vascular and wound-care teams to collaborate on prevention of ischemia after revascularization, Dr. Ennis stated. The certainty of appropriate return of macrovascular circulation must be confirmed, and all other barriers to blood flow need to be addressed.

Preoperatively, it may be possible to use free-radical scavengers or systemic vasodilators. Postoperatively, he advised that tissue-level perfusion be tested for adequacy of revascularization and cautioned against relying on the return of palpable pulse or flow in the bypass graft to do that.

Dr. Ennis disclosed that he was a consultant and received an honorarium from Celleration, which manufactures an ultrasound device for stimulation of wound healing.

WASHINGTON — The vascular surgeon insists that revascularization was a success—and there are outcome images to prove it—but the diabetic foot becomes ischemic anyway, and the wound fails to heal.

This is an all too common scenario for physicians who care for these at-risk limbs and problem wounds. Such failures can be explained in a push-pull model of perfusion in these patients, and this model may well indicate what needs to be done for effective treatment, according to Dr. William J. Ennis.

The push-pull model essentially states that despite the "push" of restored macrocirculation from revascularization, the patient still needs the ability to "pull" blood nutrients into all parts of the limb via a functional microcirculation, said Dr. Ennis of the St. James Center for Comprehensive Wound & Disease Management in Chicago. He spoke at a meeting sponsored by George Washington University Hospital.

But creating "pull" is not an easy task, especially for patients with diabetes. In such individuals, a functional microcirculation may be a problem in its own right because of both physical and physiologic changes in their microvascular system brought on by the long-term chronic disease. In patients with poor microcirculation, successful revascularization of the larger vessels can lead to ischemic reperfusion injury in the tissues that they service. White cells stick and create reactive oxygen species that make it almost impossible for wounds to heal.

Damage models in diabetic foot wound responses after revascularization can borrow from cardiology, according to Dr. Ennis—concepts such as tissue "stunning," whereby tissue is traumatized by the reperfusion injury without being killed and remains capable of recuperating; no reflow, such as that caused by a mechanical obstruction from thrombus; or functional alterations, such as the endothelial dysfunction that is known to occur in diabetics.

It is critical to restore a microvascular "pull" as soon as possible in order for the wound to heal and, in many cases, in order for the limb to survive, according to Dr. Ennis. "It is almost silly for us to think that we can solve the entire process with a simple bypass. We may end up with a mixed pattern, persistent ischemia, and something known as no reflow. These are the patients who get bypass and nothing happens—the wound continues or the open-air site never heals…. It is so frustrating for us as wound clinicians to see a great bypass and still lose a limb. It's not uncommon, and this [microcirculatory problem] is why."

Angiogenesis agents are one option for restoring microcirculatory "pull." One such treatment may be ultrasound. Pulsatile flow in tissue pushes and pulls on the endothelium and causes nitric oxide release. Ultrasound can be used to "fake the tissue out that it is receiving pulsatile flow," according to Dr. Ennis, who along with his colleagues has studied the use of ultrasound to induce angiogenesis, pulsatile flow, and ultimately wound healing.

"We were able to show that there was a difference in angiogenesis at approximately 41/2 weeks with ultrasound therapy. … This was one of the first times we were actually able to quantify the angiogenesis response and correlate it to wound healing," he explained (Advances in Skin & Wound Care 2006;19:437–46).

The future may include novel treatments for reperfusion injury and ischemia such as bone marrow stem cell therapy, which may be available in 5–10 years, and growth factor molecules, many of which are currently being tested in phase I trials, according to Dr. Ennis.

Regardless of which treatment is chosen, it is also important for the vascular and wound-care teams to collaborate on prevention of ischemia after revascularization, Dr. Ennis stated. The certainty of appropriate return of macrovascular circulation must be confirmed, and all other barriers to blood flow need to be addressed.

Preoperatively, it may be possible to use free-radical scavengers or systemic vasodilators. Postoperatively, he advised that tissue-level perfusion be tested for adequacy of revascularization and cautioned against relying on the return of palpable pulse or flow in the bypass graft to do that.

Dr. Ennis disclosed that he was a consultant and received an honorarium from Celleration, which manufactures an ultrasound device for stimulation of wound healing.

WASHINGTON — The vascular surgeon insists that revascularization was a success—and there are outcome images to prove it—but the diabetic foot becomes ischemic anyway, and the wound fails to heal.

This is an all too common scenario for physicians who care for these at-risk limbs and problem wounds. Such failures can be explained in a push-pull model of perfusion in these patients, and this model may well indicate what needs to be done for effective treatment, according to Dr. William J. Ennis.

The push-pull model essentially states that despite the "push" of restored macrocirculation from revascularization, the patient still needs the ability to "pull" blood nutrients into all parts of the limb via a functional microcirculation, said Dr. Ennis of the St. James Center for Comprehensive Wound & Disease Management in Chicago. He spoke at a meeting sponsored by George Washington University Hospital.

But creating "pull" is not an easy task, especially for patients with diabetes. In such individuals, a functional microcirculation may be a problem in its own right because of both physical and physiologic changes in their microvascular system brought on by the long-term chronic disease. In patients with poor microcirculation, successful revascularization of the larger vessels can lead to ischemic reperfusion injury in the tissues that they service. White cells stick and create reactive oxygen species that make it almost impossible for wounds to heal.

Damage models in diabetic foot wound responses after revascularization can borrow from cardiology, according to Dr. Ennis—concepts such as tissue "stunning," whereby tissue is traumatized by the reperfusion injury without being killed and remains capable of recuperating; no reflow, such as that caused by a mechanical obstruction from thrombus; or functional alterations, such as the endothelial dysfunction that is known to occur in diabetics.

It is critical to restore a microvascular "pull" as soon as possible in order for the wound to heal and, in many cases, in order for the limb to survive, according to Dr. Ennis. "It is almost silly for us to think that we can solve the entire process with a simple bypass. We may end up with a mixed pattern, persistent ischemia, and something known as no reflow. These are the patients who get bypass and nothing happens—the wound continues or the open-air site never heals…. It is so frustrating for us as wound clinicians to see a great bypass and still lose a limb. It's not uncommon, and this [microcirculatory problem] is why."

Angiogenesis agents are one option for restoring microcirculatory "pull." One such treatment may be ultrasound. Pulsatile flow in tissue pushes and pulls on the endothelium and causes nitric oxide release. Ultrasound can be used to "fake the tissue out that it is receiving pulsatile flow," according to Dr. Ennis, who along with his colleagues has studied the use of ultrasound to induce angiogenesis, pulsatile flow, and ultimately wound healing.

"We were able to show that there was a difference in angiogenesis at approximately 41/2 weeks with ultrasound therapy. … This was one of the first times we were actually able to quantify the angiogenesis response and correlate it to wound healing," he explained (Advances in Skin & Wound Care 2006;19:437–46).

The future may include novel treatments for reperfusion injury and ischemia such as bone marrow stem cell therapy, which may be available in 5–10 years, and growth factor molecules, many of which are currently being tested in phase I trials, according to Dr. Ennis.

Regardless of which treatment is chosen, it is also important for the vascular and wound-care teams to collaborate on prevention of ischemia after revascularization, Dr. Ennis stated. The certainty of appropriate return of macrovascular circulation must be confirmed, and all other barriers to blood flow need to be addressed.

Preoperatively, it may be possible to use free-radical scavengers or systemic vasodilators. Postoperatively, he advised that tissue-level perfusion be tested for adequacy of revascularization and cautioned against relying on the return of palpable pulse or flow in the bypass graft to do that.

Dr. Ennis disclosed that he was a consultant and received an honorarium from Celleration, which manufactures an ultrasound device for stimulation of wound healing.

Diabetic retinopathy and coronary artery disease appear highly associated, and the severity of the retinopathy is correlated with a graded, increased risk of death from CAD or myocardial infarction, according to a literature review.

Patients with diabetic retinopathy, despite their increased risk, also appear to have significant underdiagnosis of the presence of CAD, the reviewers said.

Coronary artery bypass grafting (CABG) appears to provide better survival outcomes than percutaneous coronary intervention (PCI) when treating patients with diabetic retinopathy. In addition, CABG delivers greater survival benefits when performed before diabetic retinopathy becomes severe, according to Dr. Takayuki Ohno and colleagues from the department of cardiothoracic surgery, the University of Tokyo (Ann. Thorac. Surg. 2008;85:681–9).

The researchers included all cohort, case-controlled, cross-sectional, and experimental studies that evaluated the association of diabetic retinopathy and CAD in the Medline database published from January 1996 to July 2007. They also searched secondary sources manually. All papers were in English.

The studies reviewed showed that patients with advanced diabetic retinopathy have a poor life expectancy. In one retrospective study of 128 diabetic patients, the 5-year mortality was 45% in patients with proliferative diabetic retinopathy (PDR) and 8% for those without retinopathy. In a second prospective study of 709 patients with type 2 diabetes, the 5-year mortality was 44% for those with non-PDR (NPDR) and 1% for those with little or no retinopathy at baseline.

Mortality is primarily associated with CAD, according to other reports. For example, the Wisconsin Epidemiologic Study of Diabetic Retinopathy followed 1,370 older-onset diabetes mellitus patients for an average of 8.5 years. Researchers found the age- and sex-adjusted hazard ratios for CAD mortality were 1.50 for patients with mild NPDR, 1.93 in patients with moderate NPDR, and 2.07 in those with PDR. In that same study, 996 patients with type 1 diabetes were also followed and 20-year cumulative self-reported incidence of myocardial infarction was 6.0% for those without retinopathy, 9.5% for early NPDR, 21% for moderate to severe NPDR, and 26% for PDR.

The authors also reported studies showing that heart failure was more likely to develop in patients with diabetic retinopathy experiencing acute MI than in those patients without retinopathy. Of particular significance given these mortality and MI risks was the fact that several studies showed that approximately 20% of asymptomatic patients with diabetic retinopathy and normal resting electrocardiograms had CAD. The disease is often asymptomatic until the catastrophic events of overt heart failure or sudden death, the authors stated.

Coronary revascularization (either with CABG or PCI) is the mainstay of treatment for CAD, according to the authors, and this is of particular concern to patients with diabetic retinopathy.

Dr. Ohno and colleagues cited data from the Bypass Angioplasty Revascularization Investigation (BARI), which showed that at 5-year follow-up, there were 15 excess deaths for every 100 diabetic patients revascularized by PCI rather than CABG, 20 excess deaths at 7 years, and 22 at 10 years. They stated that, “in the real world, the presence of diabetes does not influence treatment decisions regarding revascularization in patients with stable CAD” because of the perceived benefits to patients of local anesthetic and minimal postprocedural morbidity.

But CABG alone is not enough, according to the authors. Timing is also important. They reported a retrospective study of 223 diabetic patients undergoing CABG. The 12-year survival was 82% for patients without retinopathy, 56% for patients with mild to moderate NPDR, 36% for patients with severe NPDR, and 12% for those with PDR. These data indicate that patients should be treated with CABG early before retinopathy becomes more severe, they stated.

Diabetic retinopathy should thus be considered not only as a sign for intensive monitoring of possible CAD, but also as a guide for developing an appropriate coronary revascularization study, the authors said.

Diabetic retinopathy and coronary artery disease appear highly associated, and the severity of the retinopathy is correlated with a graded, increased risk of death from CAD or myocardial infarction, according to a literature review.

Patients with diabetic retinopathy, despite their increased risk, also appear to have significant underdiagnosis of the presence of CAD, the reviewers said.

Coronary artery bypass grafting (CABG) appears to provide better survival outcomes than percutaneous coronary intervention (PCI) when treating patients with diabetic retinopathy. In addition, CABG delivers greater survival benefits when performed before diabetic retinopathy becomes severe, according to Dr. Takayuki Ohno and colleagues from the department of cardiothoracic surgery, the University of Tokyo (Ann. Thorac. Surg. 2008;85:681–9).

The researchers included all cohort, case-controlled, cross-sectional, and experimental studies that evaluated the association of diabetic retinopathy and CAD in the Medline database published from January 1996 to July 2007. They also searched secondary sources manually. All papers were in English.

The studies reviewed showed that patients with advanced diabetic retinopathy have a poor life expectancy. In one retrospective study of 128 diabetic patients, the 5-year mortality was 45% in patients with proliferative diabetic retinopathy (PDR) and 8% for those without retinopathy. In a second prospective study of 709 patients with type 2 diabetes, the 5-year mortality was 44% for those with non-PDR (NPDR) and 1% for those with little or no retinopathy at baseline.

Mortality is primarily associated with CAD, according to other reports. For example, the Wisconsin Epidemiologic Study of Diabetic Retinopathy followed 1,370 older-onset diabetes mellitus patients for an average of 8.5 years. Researchers found the age- and sex-adjusted hazard ratios for CAD mortality were 1.50 for patients with mild NPDR, 1.93 in patients with moderate NPDR, and 2.07 in those with PDR. In that same study, 996 patients with type 1 diabetes were also followed and 20-year cumulative self-reported incidence of myocardial infarction was 6.0% for those without retinopathy, 9.5% for early NPDR, 21% for moderate to severe NPDR, and 26% for PDR.

The authors also reported studies showing that heart failure was more likely to develop in patients with diabetic retinopathy experiencing acute MI than in those patients without retinopathy. Of particular significance given these mortality and MI risks was the fact that several studies showed that approximately 20% of asymptomatic patients with diabetic retinopathy and normal resting electrocardiograms had CAD. The disease is often asymptomatic until the catastrophic events of overt heart failure or sudden death, the authors stated.

Coronary revascularization (either with CABG or PCI) is the mainstay of treatment for CAD, according to the authors, and this is of particular concern to patients with diabetic retinopathy.

Dr. Ohno and colleagues cited data from the Bypass Angioplasty Revascularization Investigation (BARI), which showed that at 5-year follow-up, there were 15 excess deaths for every 100 diabetic patients revascularized by PCI rather than CABG, 20 excess deaths at 7 years, and 22 at 10 years. They stated that, “in the real world, the presence of diabetes does not influence treatment decisions regarding revascularization in patients with stable CAD” because of the perceived benefits to patients of local anesthetic and minimal postprocedural morbidity.

But CABG alone is not enough, according to the authors. Timing is also important. They reported a retrospective study of 223 diabetic patients undergoing CABG. The 12-year survival was 82% for patients without retinopathy, 56% for patients with mild to moderate NPDR, 36% for patients with severe NPDR, and 12% for those with PDR. These data indicate that patients should be treated with CABG early before retinopathy becomes more severe, they stated.

Diabetic retinopathy should thus be considered not only as a sign for intensive monitoring of possible CAD, but also as a guide for developing an appropriate coronary revascularization study, the authors said.

Diabetic retinopathy and coronary artery disease appear highly associated, and the severity of the retinopathy is correlated with a graded, increased risk of death from CAD or myocardial infarction, according to a literature review.

Patients with diabetic retinopathy, despite their increased risk, also appear to have significant underdiagnosis of the presence of CAD, the reviewers said.

Coronary artery bypass grafting (CABG) appears to provide better survival outcomes than percutaneous coronary intervention (PCI) when treating patients with diabetic retinopathy. In addition, CABG delivers greater survival benefits when performed before diabetic retinopathy becomes severe, according to Dr. Takayuki Ohno and colleagues from the department of cardiothoracic surgery, the University of Tokyo (Ann. Thorac. Surg. 2008;85:681–9).

The researchers included all cohort, case-controlled, cross-sectional, and experimental studies that evaluated the association of diabetic retinopathy and CAD in the Medline database published from January 1996 to July 2007. They also searched secondary sources manually. All papers were in English.

The studies reviewed showed that patients with advanced diabetic retinopathy have a poor life expectancy. In one retrospective study of 128 diabetic patients, the 5-year mortality was 45% in patients with proliferative diabetic retinopathy (PDR) and 8% for those without retinopathy. In a second prospective study of 709 patients with type 2 diabetes, the 5-year mortality was 44% for those with non-PDR (NPDR) and 1% for those with little or no retinopathy at baseline.

Mortality is primarily associated with CAD, according to other reports. For example, the Wisconsin Epidemiologic Study of Diabetic Retinopathy followed 1,370 older-onset diabetes mellitus patients for an average of 8.5 years. Researchers found the age- and sex-adjusted hazard ratios for CAD mortality were 1.50 for patients with mild NPDR, 1.93 in patients with moderate NPDR, and 2.07 in those with PDR. In that same study, 996 patients with type 1 diabetes were also followed and 20-year cumulative self-reported incidence of myocardial infarction was 6.0% for those without retinopathy, 9.5% for early NPDR, 21% for moderate to severe NPDR, and 26% for PDR.

The authors also reported studies showing that heart failure was more likely to develop in patients with diabetic retinopathy experiencing acute MI than in those patients without retinopathy. Of particular significance given these mortality and MI risks was the fact that several studies showed that approximately 20% of asymptomatic patients with diabetic retinopathy and normal resting electrocardiograms had CAD. The disease is often asymptomatic until the catastrophic events of overt heart failure or sudden death, the authors stated.

Coronary revascularization (either with CABG or PCI) is the mainstay of treatment for CAD, according to the authors, and this is of particular concern to patients with diabetic retinopathy.

Dr. Ohno and colleagues cited data from the Bypass Angioplasty Revascularization Investigation (BARI), which showed that at 5-year follow-up, there were 15 excess deaths for every 100 diabetic patients revascularized by PCI rather than CABG, 20 excess deaths at 7 years, and 22 at 10 years. They stated that, “in the real world, the presence of diabetes does not influence treatment decisions regarding revascularization in patients with stable CAD” because of the perceived benefits to patients of local anesthetic and minimal postprocedural morbidity.

But CABG alone is not enough, according to the authors. Timing is also important. They reported a retrospective study of 223 diabetic patients undergoing CABG. The 12-year survival was 82% for patients without retinopathy, 56% for patients with mild to moderate NPDR, 36% for patients with severe NPDR, and 12% for those with PDR. These data indicate that patients should be treated with CABG early before retinopathy becomes more severe, they stated.

Diabetic retinopathy should thus be considered not only as a sign for intensive monitoring of possible CAD, but also as a guide for developing an appropriate coronary revascularization study, the authors said.

WASHINGTON — Monotherapy may not be enough in the treatment of diabetic wound infections.

These infections are not caused by the planktonic or individual cellular form of mainly single-species bacteria proliferating in the wound, but rather are caused by a complex, multicell vegetative mixed-bacterial state known as a biofilm, which has to be treated as a unique and dangerous organism in its own right, if treatment is to prove effective, Dr. Randall Wolcott said at a meeting sponsored by George Washington University Hospital.

The medical biofilm concept of infection is a fairly new one, and a recent review noted that almost every bodily system is affected by a biofilm disease. He estimated that every year, more than 10 million people come down with biofilm diseases, from endocarditis to necrotizing fasciitis.

This translates to more than 500,000 people a year who die from a biofilm disease, and it is time practitioners realized that the infected diabetic foot wound is a biofilm disease as well, in order to treat it appropriately, said Dr. Wolcott of the department of microbiology and immunology at Texas Tech University, Lubbock, and the Southwest Regional Wound Care Center in that city.

He used the dramatic imagery from the science fiction movie “Terminator II,” in which a killer police officer, made of liquid metal, is first shattered into pieces and yet quickly reassembles with equal destructive capability as before.

The behavior of biofilms is similar, he pointed out. Once bacteria attach to a wounded surface, “they form a microcolony. Once they reach a critical density, they start form-sensing, and they rise up above the surface and they start forming all these complex structures. One of those structures infests itself around the vasculature and they invade the host down through the vascular system. [They also] rise up over the surface for community defenses,” he said.

This vegetative state behaves like a single organism “made of billions of billions of cells” including multiple bacterial species. A large portion of this “organism”—and he stressed treating it as such—includes gluey, sugar-protein matrices formed within the first 5 minutes of biofilm development. These protect the bacteria from harm by walling them off—not only from the host immune system, but also from many of the treatments that are used, Dr. Wolcott said.

Within 30 minutes, the biofilm is rising from the surface. It is controlled centrally by various intercellular communication molecules that act almost like hormones, and it reproduces by vegetative breaking and single-cell “seeds.” The biofilm components summon white blood cells, with their phagocytic enzymes, which actually can provide nutrients for the biofilm; this explains much of the biochemistry we see, according to Dr. Wolcott.

The bacteria give up their individuality and live for the colony, with different regions producing different proteins, just as organisms have different brain cells, liver cells, and so on. One clinically important factor is that there are portions of the biofilm where the cells upregulate gene transfer to create phenotypic and genotypic diversity to survive. This includes the potential for transferring antibiotic resistance across species.

This understanding is very new, Dr. Wolcott said. “I just got a [2007] medical microbiology text and it does not mention biofilms,” he noted, suggesting maybe that was why most of the audience might not have heard of these concepts.

However, practitioners did see biofilms in diabetic foot wounds every day without realizing it: the so-called slough that physicians routinely remove, or not, Dr. Wolcott added. Many believe slough is merely some mixture of white blood cells, protein, and deteriorated host tissue, but it is actually part of a complex biofilm—and one that will return exactly as before if even “one cell remains” still virulent, exactly as before without proper treatment.

“If I take off waxy biofilm … then I get waxy biofilm back. If I take off the fluffy biofilm I get the fluffy,” he said. “So slough really is biofilm.”

And if all these infections are really biofilms, then the next therapeutic step is to move from antibiotic monotherapies to include the use of antibiofilm agents and aggressive treatments, Dr. Wolcott said. This combined treatment is only in its infancy. It involves frequent, very aggressive debridement, coupled with biocide treatments that include heavy metal agents such as silver, gallium, and selenium. It is important to rotate treatments in order to prevent selective adaptation of the biofilm, which can happen not in weeks or months, but in days.

In his practice, he also thinks it critical to include the use of specific antibiofilm agents such as lactoferrin and xylitol, which are approved by the Food and Drug Administration for other purposes. He has even experimentally used predatory bacteriophages and various plant extracts known for their antibiofilm properties. Ultimately, “once you suppress the biofilm below a certain level … the wound starts contracting” and normal host healing can begin, he said.

Dr. Wolcott had no disclosures other than the use of materials that are not FDA approved for these indications.

WASHINGTON — Monotherapy may not be enough in the treatment of diabetic wound infections.

These infections are not caused by the planktonic or individual cellular form of mainly single-species bacteria proliferating in the wound, but rather are caused by a complex, multicell vegetative mixed-bacterial state known as a biofilm, which has to be treated as a unique and dangerous organism in its own right, if treatment is to prove effective, Dr. Randall Wolcott said at a meeting sponsored by George Washington University Hospital.

The medical biofilm concept of infection is a fairly new one, and a recent review noted that almost every bodily system is affected by a biofilm disease. He estimated that every year, more than 10 million people come down with biofilm diseases, from endocarditis to necrotizing fasciitis.

This translates to more than 500,000 people a year who die from a biofilm disease, and it is time practitioners realized that the infected diabetic foot wound is a biofilm disease as well, in order to treat it appropriately, said Dr. Wolcott of the department of microbiology and immunology at Texas Tech University, Lubbock, and the Southwest Regional Wound Care Center in that city.

He used the dramatic imagery from the science fiction movie “Terminator II,” in which a killer police officer, made of liquid metal, is first shattered into pieces and yet quickly reassembles with equal destructive capability as before.

The behavior of biofilms is similar, he pointed out. Once bacteria attach to a wounded surface, “they form a microcolony. Once they reach a critical density, they start form-sensing, and they rise up above the surface and they start forming all these complex structures. One of those structures infests itself around the vasculature and they invade the host down through the vascular system. [They also] rise up over the surface for community defenses,” he said.

This vegetative state behaves like a single organism “made of billions of billions of cells” including multiple bacterial species. A large portion of this “organism”—and he stressed treating it as such—includes gluey, sugar-protein matrices formed within the first 5 minutes of biofilm development. These protect the bacteria from harm by walling them off—not only from the host immune system, but also from many of the treatments that are used, Dr. Wolcott said.

Within 30 minutes, the biofilm is rising from the surface. It is controlled centrally by various intercellular communication molecules that act almost like hormones, and it reproduces by vegetative breaking and single-cell “seeds.” The biofilm components summon white blood cells, with their phagocytic enzymes, which actually can provide nutrients for the biofilm; this explains much of the biochemistry we see, according to Dr. Wolcott.

The bacteria give up their individuality and live for the colony, with different regions producing different proteins, just as organisms have different brain cells, liver cells, and so on. One clinically important factor is that there are portions of the biofilm where the cells upregulate gene transfer to create phenotypic and genotypic diversity to survive. This includes the potential for transferring antibiotic resistance across species.

This understanding is very new, Dr. Wolcott said. “I just got a [2007] medical microbiology text and it does not mention biofilms,” he noted, suggesting maybe that was why most of the audience might not have heard of these concepts.

However, practitioners did see biofilms in diabetic foot wounds every day without realizing it: the so-called slough that physicians routinely remove, or not, Dr. Wolcott added. Many believe slough is merely some mixture of white blood cells, protein, and deteriorated host tissue, but it is actually part of a complex biofilm—and one that will return exactly as before if even “one cell remains” still virulent, exactly as before without proper treatment.

“If I take off waxy biofilm … then I get waxy biofilm back. If I take off the fluffy biofilm I get the fluffy,” he said. “So slough really is biofilm.”

And if all these infections are really biofilms, then the next therapeutic step is to move from antibiotic monotherapies to include the use of antibiofilm agents and aggressive treatments, Dr. Wolcott said. This combined treatment is only in its infancy. It involves frequent, very aggressive debridement, coupled with biocide treatments that include heavy metal agents such as silver, gallium, and selenium. It is important to rotate treatments in order to prevent selective adaptation of the biofilm, which can happen not in weeks or months, but in days.

In his practice, he also thinks it critical to include the use of specific antibiofilm agents such as lactoferrin and xylitol, which are approved by the Food and Drug Administration for other purposes. He has even experimentally used predatory bacteriophages and various plant extracts known for their antibiofilm properties. Ultimately, “once you suppress the biofilm below a certain level … the wound starts contracting” and normal host healing can begin, he said.

Dr. Wolcott had no disclosures other than the use of materials that are not FDA approved for these indications.

WASHINGTON — Monotherapy may not be enough in the treatment of diabetic wound infections.

These infections are not caused by the planktonic or individual cellular form of mainly single-species bacteria proliferating in the wound, but rather are caused by a complex, multicell vegetative mixed-bacterial state known as a biofilm, which has to be treated as a unique and dangerous organism in its own right, if treatment is to prove effective, Dr. Randall Wolcott said at a meeting sponsored by George Washington University Hospital.

The medical biofilm concept of infection is a fairly new one, and a recent review noted that almost every bodily system is affected by a biofilm disease. He estimated that every year, more than 10 million people come down with biofilm diseases, from endocarditis to necrotizing fasciitis.

This translates to more than 500,000 people a year who die from a biofilm disease, and it is time practitioners realized that the infected diabetic foot wound is a biofilm disease as well, in order to treat it appropriately, said Dr. Wolcott of the department of microbiology and immunology at Texas Tech University, Lubbock, and the Southwest Regional Wound Care Center in that city.

He used the dramatic imagery from the science fiction movie “Terminator II,” in which a killer police officer, made of liquid metal, is first shattered into pieces and yet quickly reassembles with equal destructive capability as before.

The behavior of biofilms is similar, he pointed out. Once bacteria attach to a wounded surface, “they form a microcolony. Once they reach a critical density, they start form-sensing, and they rise up above the surface and they start forming all these complex structures. One of those structures infests itself around the vasculature and they invade the host down through the vascular system. [They also] rise up over the surface for community defenses,” he said.

This vegetative state behaves like a single organism “made of billions of billions of cells” including multiple bacterial species. A large portion of this “organism”—and he stressed treating it as such—includes gluey, sugar-protein matrices formed within the first 5 minutes of biofilm development. These protect the bacteria from harm by walling them off—not only from the host immune system, but also from many of the treatments that are used, Dr. Wolcott said.

Within 30 minutes, the biofilm is rising from the surface. It is controlled centrally by various intercellular communication molecules that act almost like hormones, and it reproduces by vegetative breaking and single-cell “seeds.” The biofilm components summon white blood cells, with their phagocytic enzymes, which actually can provide nutrients for the biofilm; this explains much of the biochemistry we see, according to Dr. Wolcott.

The bacteria give up their individuality and live for the colony, with different regions producing different proteins, just as organisms have different brain cells, liver cells, and so on. One clinically important factor is that there are portions of the biofilm where the cells upregulate gene transfer to create phenotypic and genotypic diversity to survive. This includes the potential for transferring antibiotic resistance across species.

This understanding is very new, Dr. Wolcott said. “I just got a [2007] medical microbiology text and it does not mention biofilms,” he noted, suggesting maybe that was why most of the audience might not have heard of these concepts.

However, practitioners did see biofilms in diabetic foot wounds every day without realizing it: the so-called slough that physicians routinely remove, or not, Dr. Wolcott added. Many believe slough is merely some mixture of white blood cells, protein, and deteriorated host tissue, but it is actually part of a complex biofilm—and one that will return exactly as before if even “one cell remains” still virulent, exactly as before without proper treatment.

“If I take off waxy biofilm … then I get waxy biofilm back. If I take off the fluffy biofilm I get the fluffy,” he said. “So slough really is biofilm.”

And if all these infections are really biofilms, then the next therapeutic step is to move from antibiotic monotherapies to include the use of antibiofilm agents and aggressive treatments, Dr. Wolcott said. This combined treatment is only in its infancy. It involves frequent, very aggressive debridement, coupled with biocide treatments that include heavy metal agents such as silver, gallium, and selenium. It is important to rotate treatments in order to prevent selective adaptation of the biofilm, which can happen not in weeks or months, but in days.

In his practice, he also thinks it critical to include the use of specific antibiofilm agents such as lactoferrin and xylitol, which are approved by the Food and Drug Administration for other purposes. He has even experimentally used predatory bacteriophages and various plant extracts known for their antibiofilm properties. Ultimately, “once you suppress the biofilm below a certain level … the wound starts contracting” and normal host healing can begin, he said.

Dr. Wolcott had no disclosures other than the use of materials that are not FDA approved for these indications.

WASHINGTON — Monotherapy may not be enough in the treatment of diabetic wound infections.

These infections are not caused by the planktonic or individual cellular form of mainly single-species bacteria proliferating in the wound, but rather are caused by a complex, multicell vegetative mixed-bacterial state known as a biofilm, which has to be treated as a unique and dangerous organism in its own right, if treatment is to prove effective, according to Dr. Randall Wolcott, of the department of microbiology and immunology at Texas Tech University, Lubbock.

The medical biofilm concept of infection is a fairly new one, and a recent review noted that almost every bodily system is affected by a biofilm disease, said Dr. Wolcott at a meeting sponsored by George Washington University Hospital.

He estimated that every year, more than 10 million people come down with biofilm diseases, from endocarditis to necrotizing fasciitis, which translates to more than 500,000 people a year who die from the disease.

And if all these infections are really biofilms, then the next therapeutic step is to move from antibiotic monotherapies to include the use of antibiofilm agents and aggressive treatments, Dr. Wolcott said.

His recommended combined treatment is only in its infancy, but it involves frequent, very aggressive debridement, coupled with biocide treatments that include heavy metal agents such as silver, gallium, and selenium. It is important to rotate treatments in order to prevent selective adaptation of the biofilm, which can happen not in weeks or months, but in days.

It is also critical to include the use of specific antibiofilm agents such as lactoferrin and xylitol, which are approved by the Food and Drug Administration for other purposes. He has even experimentally used predatory bacteriophages and various plant extracts known for their antibiofilm properties. Ultimately, "once you suppress the biofilm below a certain level … the wound starts contracting" and normal host healing can begin, he said.

This understanding is very new, and few people are being trained enough to understand it as yet. "I just got a [2007] medical microbiology text and it does not mention biofilms," he said.

However, physicians see biofilms in diabetic foot wounds every day without realizing it: the so-called slough that physicians routinely remove, or not, said Dr. Wolcott. Many physicians believe slough is merely a mixture of white blood cells, protein, and deteriorated host tissue, but it is actually part of a complex biofilm—and one that will return, if even "one cell remains" still virulent, exactly as before without proper treatment.

Once bacteria attach to a wounded surface, "they form a microcolony. Once they reach a critical density, they start form-sensing, and they rise up above the surface and they start forming all these complex structures. One of those structures infests itself around the vasculature and they invade the host down through the vascular system. [They also] rise up over the surface for community defenses," he said.

This vegetative state behaves like a single organism "made of billions of billions of cells" including multiple bacterial species. A large portion of this "organism"—and he stressed treating it as such—includes gluey, sugar-protein matrices formed within the first 5 minutes of biofilm development. These protect the bacteria from harm by walling them off—not only from the host immune system, but also from many of the treatments that are used, Dr. Wolcott said.

Within 30 minutes, the biofilm is rising from the surface. It is controlled centrally by various intercellular communication molecules that act almost like hormones, and it reproduces by vegetative breaking and single-cell "seeds."

The biofilm components summon white blood cells, with their phagocytic enzymes, which actually can provide nutrients for the biofilm; this explains much of the biochemistry we see, according to Dr. Wolcott.

The bacteria give up their individuality and live for the colony, with different regions producing different proteins. One clinically important factor is that there are portions of the biofilm where the cells upregulate gene transfer to create phenotypic and genotypic diversity to survive. This includes the potential for transferring antibiotic resistance across species.

Dr. Wolcott had no disclosures other than the use of materials that are not FDA approved for these indications.

WASHINGTON — Monotherapy may not be enough in the treatment of diabetic wound infections.

These infections are not caused by the planktonic or individual cellular form of mainly single-species bacteria proliferating in the wound, but rather are caused by a complex, multicell vegetative mixed-bacterial state known as a biofilm, which has to be treated as a unique and dangerous organism in its own right, if treatment is to prove effective, according to Dr. Randall Wolcott, of the department of microbiology and immunology at Texas Tech University, Lubbock.

The medical biofilm concept of infection is a fairly new one, and a recent review noted that almost every bodily system is affected by a biofilm disease, said Dr. Wolcott at a meeting sponsored by George Washington University Hospital.

He estimated that every year, more than 10 million people come down with biofilm diseases, from endocarditis to necrotizing fasciitis, which translates to more than 500,000 people a year who die from the disease.

And if all these infections are really biofilms, then the next therapeutic step is to move from antibiotic monotherapies to include the use of antibiofilm agents and aggressive treatments, Dr. Wolcott said.

His recommended combined treatment is only in its infancy, but it involves frequent, very aggressive debridement, coupled with biocide treatments that include heavy metal agents such as silver, gallium, and selenium. It is important to rotate treatments in order to prevent selective adaptation of the biofilm, which can happen not in weeks or months, but in days.

It is also critical to include the use of specific antibiofilm agents such as lactoferrin and xylitol, which are approved by the Food and Drug Administration for other purposes. He has even experimentally used predatory bacteriophages and various plant extracts known for their antibiofilm properties. Ultimately, "once you suppress the biofilm below a certain level … the wound starts contracting" and normal host healing can begin, he said.

This understanding is very new, and few people are being trained enough to understand it as yet. "I just got a [2007] medical microbiology text and it does not mention biofilms," he said.

However, physicians see biofilms in diabetic foot wounds every day without realizing it: the so-called slough that physicians routinely remove, or not, said Dr. Wolcott. Many physicians believe slough is merely a mixture of white blood cells, protein, and deteriorated host tissue, but it is actually part of a complex biofilm—and one that will return, if even "one cell remains" still virulent, exactly as before without proper treatment.

Once bacteria attach to a wounded surface, "they form a microcolony. Once they reach a critical density, they start form-sensing, and they rise up above the surface and they start forming all these complex structures. One of those structures infests itself around the vasculature and they invade the host down through the vascular system. [They also] rise up over the surface for community defenses," he said.

This vegetative state behaves like a single organism "made of billions of billions of cells" including multiple bacterial species. A large portion of this "organism"—and he stressed treating it as such—includes gluey, sugar-protein matrices formed within the first 5 minutes of biofilm development. These protect the bacteria from harm by walling them off—not only from the host immune system, but also from many of the treatments that are used, Dr. Wolcott said.

Within 30 minutes, the biofilm is rising from the surface. It is controlled centrally by various intercellular communication molecules that act almost like hormones, and it reproduces by vegetative breaking and single-cell "seeds."

The biofilm components summon white blood cells, with their phagocytic enzymes, which actually can provide nutrients for the biofilm; this explains much of the biochemistry we see, according to Dr. Wolcott.

The bacteria give up their individuality and live for the colony, with different regions producing different proteins. One clinically important factor is that there are portions of the biofilm where the cells upregulate gene transfer to create phenotypic and genotypic diversity to survive. This includes the potential for transferring antibiotic resistance across species.

Dr. Wolcott had no disclosures other than the use of materials that are not FDA approved for these indications.

WASHINGTON — Monotherapy may not be enough in the treatment of diabetic wound infections.

These infections are not caused by the planktonic or individual cellular form of mainly single-species bacteria proliferating in the wound, but rather are caused by a complex, multicell vegetative mixed-bacterial state known as a biofilm, which has to be treated as a unique and dangerous organism in its own right, if treatment is to prove effective, according to Dr. Randall Wolcott, of the department of microbiology and immunology at Texas Tech University, Lubbock.

The medical biofilm concept of infection is a fairly new one, and a recent review noted that almost every bodily system is affected by a biofilm disease, said Dr. Wolcott at a meeting sponsored by George Washington University Hospital.

He estimated that every year, more than 10 million people come down with biofilm diseases, from endocarditis to necrotizing fasciitis, which translates to more than 500,000 people a year who die from the disease.

And if all these infections are really biofilms, then the next therapeutic step is to move from antibiotic monotherapies to include the use of antibiofilm agents and aggressive treatments, Dr. Wolcott said.

His recommended combined treatment is only in its infancy, but it involves frequent, very aggressive debridement, coupled with biocide treatments that include heavy metal agents such as silver, gallium, and selenium. It is important to rotate treatments in order to prevent selective adaptation of the biofilm, which can happen not in weeks or months, but in days.

It is also critical to include the use of specific antibiofilm agents such as lactoferrin and xylitol, which are approved by the Food and Drug Administration for other purposes. He has even experimentally used predatory bacteriophages and various plant extracts known for their antibiofilm properties. Ultimately, "once you suppress the biofilm below a certain level … the wound starts contracting" and normal host healing can begin, he said.

This understanding is very new, and few people are being trained enough to understand it as yet. "I just got a [2007] medical microbiology text and it does not mention biofilms," he said.

However, physicians see biofilms in diabetic foot wounds every day without realizing it: the so-called slough that physicians routinely remove, or not, said Dr. Wolcott. Many physicians believe slough is merely a mixture of white blood cells, protein, and deteriorated host tissue, but it is actually part of a complex biofilm—and one that will return, if even "one cell remains" still virulent, exactly as before without proper treatment.

Once bacteria attach to a wounded surface, "they form a microcolony. Once they reach a critical density, they start form-sensing, and they rise up above the surface and they start forming all these complex structures. One of those structures infests itself around the vasculature and they invade the host down through the vascular system. [They also] rise up over the surface for community defenses," he said.

This vegetative state behaves like a single organism "made of billions of billions of cells" including multiple bacterial species. A large portion of this "organism"—and he stressed treating it as such—includes gluey, sugar-protein matrices formed within the first 5 minutes of biofilm development. These protect the bacteria from harm by walling them off—not only from the host immune system, but also from many of the treatments that are used, Dr. Wolcott said.

Within 30 minutes, the biofilm is rising from the surface. It is controlled centrally by various intercellular communication molecules that act almost like hormones, and it reproduces by vegetative breaking and single-cell "seeds."

The biofilm components summon white blood cells, with their phagocytic enzymes, which actually can provide nutrients for the biofilm; this explains much of the biochemistry we see, according to Dr. Wolcott.

The bacteria give up their individuality and live for the colony, with different regions producing different proteins. One clinically important factor is that there are portions of the biofilm where the cells upregulate gene transfer to create phenotypic and genotypic diversity to survive. This includes the potential for transferring antibiotic resistance across species.

Dr. Wolcott had no disclosures other than the use of materials that are not FDA approved for these indications.

WASHINGTON — Occlusive small vessel disease in patients with diabetes does not exist, and belief in this condition has often interfered with successful treatment of the diabetic foot.

This “nonexistent disease” provides an easy explanation for wound care practitioners who have patients with a palpable pulse, but with ulcers that do not heal; it also provides an excuse for vascular surgeons who have performed what appear to be successful bypasses that still have no effect on wound healing. They can say “it's not going to work because the blood has nowhere to go,” and then withhold treatment from other patients in the future based upon this mistaken belief, according to Dr. Anton Sidawy who spoke at a meeting sponsored by Georgetown University Hospital, Washington, D.C.

“Unfortunately, this misconception caused a lot of legs to be amputated,” added Dr. Sidawy, who is chief of surgery at the Veterans Affairs Medical Center in Washington.

In 1964, researchers did a randomized study and found no differences in the presence of this so-called occlusive material between healthy patients and those with diabetes. Other researchers did arterial casts and vasodilation experiments and also found no occlusive disease. “Thus there is no more occlusion in the distal arteries and capillaries of the diabetic patient compared to nondiabetic patients,” he said.

However, there is an actual small vessel disease, Dr. Sidawy stated. It is not an occlusion—the lumen remains open—but it involves a thickening of the capillary walls that leads to a problem in the exchange of nutrients. However, the transport of oxygen is not impaired; thus, a bypass can still be of benefit.

Diabetes patients do, in fact, more frequently have occlusive disease, compared with nondiabetics, but it is not occlusion in their distal circulation; instead, it is an occlusion of the tibial arteries that Dr. Sidawy and his colleagues have come to consider to be fairly characteristic of these patients. This very anatomy allows a bypass of the occluded area all the way down to the nonoccluded feet.

One explanation of this frequency of occlusion, he pointed out, relates to the fact that diabetes patients have an independent risk for atherosclerosis, which current theories believe to be signaled by the proliferation of smooth muscle cells.

Blood vessels in type 2 diabetes patients (the most common type seen in current practice) are constantly bathed by high glucose and insulin, primarily because these patients have higher resistance to insulin, which contributes to the accumulation of both glucose and insulin in the blood.

This phenomenon led to Dr. Sidawy's group asking whether there was any interaction between this high glucose and the high insulin to cause atherosclerosis. As they amputated legs from diabetes patients and those with prediabetes, they took out the complete tibial arteries, separated the smooth muscle cells, and exposed them to different concentrations of glucose and different concentrations of insulin.

The vascular smooth muscle cells proliferated in the presence of differing concentrations of both insulin and glucose separately. Proliferation also increased more as glucose was increased up to 200 mg/dL for each level of insulin (100 ng/mL vs. 1000 ng/mL).

So glucose and insulin act together to cause the proliferation of smooth muscle cells, Dr. Sidawy said, which may help to explain some of the added risk of atherosclerosis and tibial occlusion in these patients.

Dr. Sidawy emphasized that despite factors promoting atherosclerosis in patients with diabetes, recent studies have shown that these patients may actually have better early patency rates after bypass than do nondiabetic patients, and he reiterated how successful bypasses can be at healing ulcers and saving limbs.

Dr. Sidawy reported no relevant financial relationships to disclose.

'There is no more occlusion in the distal arteries and capillaries of the diabetic patient compared to non-diabetic patients.'

WASHINGTON — Occlusive small vessel disease in patients with diabetes does not exist, and belief in this condition has often interfered with successful treatment of the diabetic foot.

This “nonexistent disease” provides an easy explanation for wound care practitioners who have patients with a palpable pulse, but with ulcers that do not heal; it also provides an excuse for vascular surgeons who have performed what appear to be successful bypasses that still have no effect on wound healing. They can say “it's not going to work because the blood has nowhere to go,” and then withhold treatment from other patients in the future based upon this mistaken belief, according to Dr. Anton Sidawy who spoke at a meeting sponsored by Georgetown University Hospital, Washington, D.C.

“Unfortunately, this misconception caused a lot of legs to be amputated,” added Dr. Sidawy, who is chief of surgery at the Veterans Affairs Medical Center in Washington.

In 1964, researchers did a randomized study and found no differences in the presence of this so-called occlusive material between healthy patients and those with diabetes. Other researchers did arterial casts and vasodilation experiments and also found no occlusive disease. “Thus there is no more occlusion in the distal arteries and capillaries of the diabetic patient compared to nondiabetic patients,” he said.

However, there is an actual small vessel disease, Dr. Sidawy stated. It is not an occlusion—the lumen remains open—but it involves a thickening of the capillary walls that leads to a problem in the exchange of nutrients. However, the transport of oxygen is not impaired; thus, a bypass can still be of benefit.

Diabetes patients do, in fact, more frequently have occlusive disease, compared with nondiabetics, but it is not occlusion in their distal circulation; instead, it is an occlusion of the tibial arteries that Dr. Sidawy and his colleagues have come to consider to be fairly characteristic of these patients. This very anatomy allows a bypass of the occluded area all the way down to the nonoccluded feet.

One explanation of this frequency of occlusion, he pointed out, relates to the fact that diabetes patients have an independent risk for atherosclerosis, which current theories believe to be signaled by the proliferation of smooth muscle cells.

Blood vessels in type 2 diabetes patients (the most common type seen in current practice) are constantly bathed by high glucose and insulin, primarily because these patients have higher resistance to insulin, which contributes to the accumulation of both glucose and insulin in the blood.

This phenomenon led to Dr. Sidawy's group asking whether there was any interaction between this high glucose and the high insulin to cause atherosclerosis. As they amputated legs from diabetes patients and those with prediabetes, they took out the complete tibial arteries, separated the smooth muscle cells, and exposed them to different concentrations of glucose and different concentrations of insulin.

The vascular smooth muscle cells proliferated in the presence of differing concentrations of both insulin and glucose separately. Proliferation also increased more as glucose was increased up to 200 mg/dL for each level of insulin (100 ng/mL vs. 1000 ng/mL).

So glucose and insulin act together to cause the proliferation of smooth muscle cells, Dr. Sidawy said, which may help to explain some of the added risk of atherosclerosis and tibial occlusion in these patients.

Dr. Sidawy emphasized that despite factors promoting atherosclerosis in patients with diabetes, recent studies have shown that these patients may actually have better early patency rates after bypass than do nondiabetic patients, and he reiterated how successful bypasses can be at healing ulcers and saving limbs.

Dr. Sidawy reported no relevant financial relationships to disclose.

'There is no more occlusion in the distal arteries and capillaries of the diabetic patient compared to non-diabetic patients.'

WASHINGTON — Occlusive small vessel disease in patients with diabetes does not exist, and belief in this condition has often interfered with successful treatment of the diabetic foot.

This “nonexistent disease” provides an easy explanation for wound care practitioners who have patients with a palpable pulse, but with ulcers that do not heal; it also provides an excuse for vascular surgeons who have performed what appear to be successful bypasses that still have no effect on wound healing. They can say “it's not going to work because the blood has nowhere to go,” and then withhold treatment from other patients in the future based upon this mistaken belief, according to Dr. Anton Sidawy who spoke at a meeting sponsored by Georgetown University Hospital, Washington, D.C.

“Unfortunately, this misconception caused a lot of legs to be amputated,” added Dr. Sidawy, who is chief of surgery at the Veterans Affairs Medical Center in Washington.

In 1964, researchers did a randomized study and found no differences in the presence of this so-called occlusive material between healthy patients and those with diabetes. Other researchers did arterial casts and vasodilation experiments and also found no occlusive disease. “Thus there is no more occlusion in the distal arteries and capillaries of the diabetic patient compared to nondiabetic patients,” he said.

However, there is an actual small vessel disease, Dr. Sidawy stated. It is not an occlusion—the lumen remains open—but it involves a thickening of the capillary walls that leads to a problem in the exchange of nutrients. However, the transport of oxygen is not impaired; thus, a bypass can still be of benefit.

Diabetes patients do, in fact, more frequently have occlusive disease, compared with nondiabetics, but it is not occlusion in their distal circulation; instead, it is an occlusion of the tibial arteries that Dr. Sidawy and his colleagues have come to consider to be fairly characteristic of these patients. This very anatomy allows a bypass of the occluded area all the way down to the nonoccluded feet.

One explanation of this frequency of occlusion, he pointed out, relates to the fact that diabetes patients have an independent risk for atherosclerosis, which current theories believe to be signaled by the proliferation of smooth muscle cells.

Blood vessels in type 2 diabetes patients (the most common type seen in current practice) are constantly bathed by high glucose and insulin, primarily because these patients have higher resistance to insulin, which contributes to the accumulation of both glucose and insulin in the blood.

This phenomenon led to Dr. Sidawy's group asking whether there was any interaction between this high glucose and the high insulin to cause atherosclerosis. As they amputated legs from diabetes patients and those with prediabetes, they took out the complete tibial arteries, separated the smooth muscle cells, and exposed them to different concentrations of glucose and different concentrations of insulin.

The vascular smooth muscle cells proliferated in the presence of differing concentrations of both insulin and glucose separately. Proliferation also increased more as glucose was increased up to 200 mg/dL for each level of insulin (100 ng/mL vs. 1000 ng/mL).

So glucose and insulin act together to cause the proliferation of smooth muscle cells, Dr. Sidawy said, which may help to explain some of the added risk of atherosclerosis and tibial occlusion in these patients.

Dr. Sidawy emphasized that despite factors promoting atherosclerosis in patients with diabetes, recent studies have shown that these patients may actually have better early patency rates after bypass than do nondiabetic patients, and he reiterated how successful bypasses can be at healing ulcers and saving limbs.

Dr. Sidawy reported no relevant financial relationships to disclose.

'There is no more occlusion in the distal arteries and capillaries of the diabetic patient compared to non-diabetic patients.'

BALTIMORE — Patients who use lipid-lowering drugs showed a lower rate of growth of abdominal aortic aneurysms, compared with patients who did not use these drugs, said Dr. Felix J.V. Schlösser in a presentation at the Vascular Annual Meeting.

Patients with manifest arterial vascular disease or cardiovascular risk factors who were enrolled in the Second Manifestation of Arterial Disease (SMART) trial from between September 1996 and January 2005 all had measurements made of their abdominal aortic diameter, said Dr. Schlösser in an interview.

The subgroup of patients with AAA diameters measuring 30–55 mm were selected for this study, which was presented by Dr. Schlösser and his colleagues from the University Medical Center Utrecht (the Netherlands) in a session sponsored by the Peripheral Vascular Surgery Society.

The 230 patients averaged 66 years of age, and 90% were male. Mortality at 2 and 5 years was nearly 8% and slightly over 25%, respectively. A total of four AAA ruptures occurred, all of which were fatal and occurred in patients with AAA diameters larger than 50 mm. In 109 patients, AAA measurements were performed for longer than 6 months, with a median follow-up time of 3.3 years. The mean diameter of the AAA in these patients was 40.7 mm, with a median expansion rate of 2.8 mm/year. The only factor independently and significantly associated with AAA growth was the use of lipid-lowering drugs. Patients on lipid-lowering drugs had a plus or minus 30% millimeter per year-lower AAA growth rate, compared with patients who did not use these drugs. Confirmation by a randomized controlled trial is required, however. Lipid-lowering drugs could possibly become part of standard treatment regimens for AAA patients.

BALTIMORE — Patients who use lipid-lowering drugs showed a lower rate of growth of abdominal aortic aneurysms, compared with patients who did not use these drugs, said Dr. Felix J.V. Schlösser in a presentation at the Vascular Annual Meeting.

Patients with manifest arterial vascular disease or cardiovascular risk factors who were enrolled in the Second Manifestation of Arterial Disease (SMART) trial from between September 1996 and January 2005 all had measurements made of their abdominal aortic diameter, said Dr. Schlösser in an interview.

The subgroup of patients with AAA diameters measuring 30–55 mm were selected for this study, which was presented by Dr. Schlösser and his colleagues from the University Medical Center Utrecht (the Netherlands) in a session sponsored by the Peripheral Vascular Surgery Society.

The 230 patients averaged 66 years of age, and 90% were male. Mortality at 2 and 5 years was nearly 8% and slightly over 25%, respectively. A total of four AAA ruptures occurred, all of which were fatal and occurred in patients with AAA diameters larger than 50 mm. In 109 patients, AAA measurements were performed for longer than 6 months, with a median follow-up time of 3.3 years. The mean diameter of the AAA in these patients was 40.7 mm, with a median expansion rate of 2.8 mm/year. The only factor independently and significantly associated with AAA growth was the use of lipid-lowering drugs. Patients on lipid-lowering drugs had a plus or minus 30% millimeter per year-lower AAA growth rate, compared with patients who did not use these drugs. Confirmation by a randomized controlled trial is required, however. Lipid-lowering drugs could possibly become part of standard treatment regimens for AAA patients.

BALTIMORE — Patients who use lipid-lowering drugs showed a lower rate of growth of abdominal aortic aneurysms, compared with patients who did not use these drugs, said Dr. Felix J.V. Schlösser in a presentation at the Vascular Annual Meeting.

Patients with manifest arterial vascular disease or cardiovascular risk factors who were enrolled in the Second Manifestation of Arterial Disease (SMART) trial from between September 1996 and January 2005 all had measurements made of their abdominal aortic diameter, said Dr. Schlösser in an interview.

The subgroup of patients with AAA diameters measuring 30–55 mm were selected for this study, which was presented by Dr. Schlösser and his colleagues from the University Medical Center Utrecht (the Netherlands) in a session sponsored by the Peripheral Vascular Surgery Society.

The 230 patients averaged 66 years of age, and 90% were male. Mortality at 2 and 5 years was nearly 8% and slightly over 25%, respectively. A total of four AAA ruptures occurred, all of which were fatal and occurred in patients with AAA diameters larger than 50 mm. In 109 patients, AAA measurements were performed for longer than 6 months, with a median follow-up time of 3.3 years. The mean diameter of the AAA in these patients was 40.7 mm, with a median expansion rate of 2.8 mm/year. The only factor independently and significantly associated with AAA growth was the use of lipid-lowering drugs. Patients on lipid-lowering drugs had a plus or minus 30% millimeter per year-lower AAA growth rate, compared with patients who did not use these drugs. Confirmation by a randomized controlled trial is required, however. Lipid-lowering drugs could possibly become part of standard treatment regimens for AAA patients.

Future clinical trials may have to conform to several new procedural and reporting requirements in order for Medicare beneficiary participants to be eligible for reimbursement, if revisions to the Clinical Trial Policy national coverage determination are implemented.

Changes proposed by the Centers for Medicare and Medicaid Services would include:

▸ Requiring all trials to be registered on the National Institutes of Health ClinicalTrials.gov

▸ Requiring investigators to publish their results.

▸ Requiring the study to explicitly discuss inclusion criteria and relevant subpopulations (as defined by age, gender, race/ethnicity, socioeconomic, or other factors) in the study protocol.

▸ Adding Food and Drug Administration postapproval studies and coverage with evidence development (CED) to studies that would qualify under this policy.

▸ Paying for investigational clinical services if they are covered by Medicare outside the trial or required under CED through the national coverage determination (NCD) process.

▸ Expanding the agencies that can deem whether a trial has met the general policy standards to include all Department of Health and Human Services agencies, the Veterans Administration, and the Department of Defense.

The 30-day public commentary period began in April. The CMS will review all public comments and suggestions and incorporate them into the final published NCD no later than 60 days after the end of the comment period, and the revised policy will be effective with that publication.

The Clinical Trial Policy (to be renamed the Clinical Research Policy) was first developed in 2000 to allow Medicare to pay for certain items and services for Medicare beneficiaries involved in clinical trials.

Further details are available from the CMS coverage Web site at www.cms.hhs.gov/mcd/viewdraftdecisionmemo.asp?id=186

Future clinical trials may have to conform to several new procedural and reporting requirements in order for Medicare beneficiary participants to be eligible for reimbursement, if revisions to the Clinical Trial Policy national coverage determination are implemented.

Changes proposed by the Centers for Medicare and Medicaid Services would include:

▸ Requiring all trials to be registered on the National Institutes of Health ClinicalTrials.gov

▸ Requiring investigators to publish their results.

▸ Requiring the study to explicitly discuss inclusion criteria and relevant subpopulations (as defined by age, gender, race/ethnicity, socioeconomic, or other factors) in the study protocol.

▸ Adding Food and Drug Administration postapproval studies and coverage with evidence development (CED) to studies that would qualify under this policy.

▸ Paying for investigational clinical services if they are covered by Medicare outside the trial or required under CED through the national coverage determination (NCD) process.

▸ Expanding the agencies that can deem whether a trial has met the general policy standards to include all Department of Health and Human Services agencies, the Veterans Administration, and the Department of Defense.

The 30-day public commentary period began in April. The CMS will review all public comments and suggestions and incorporate them into the final published NCD no later than 60 days after the end of the comment period, and the revised policy will be effective with that publication.

The Clinical Trial Policy (to be renamed the Clinical Research Policy) was first developed in 2000 to allow Medicare to pay for certain items and services for Medicare beneficiaries involved in clinical trials.

Further details are available from the CMS coverage Web site at www.cms.hhs.gov/mcd/viewdraftdecisionmemo.asp?id=186

Future clinical trials may have to conform to several new procedural and reporting requirements in order for Medicare beneficiary participants to be eligible for reimbursement, if revisions to the Clinical Trial Policy national coverage determination are implemented.

Changes proposed by the Centers for Medicare and Medicaid Services would include:

▸ Requiring all trials to be registered on the National Institutes of Health ClinicalTrials.gov

▸ Requiring investigators to publish their results.

▸ Requiring the study to explicitly discuss inclusion criteria and relevant subpopulations (as defined by age, gender, race/ethnicity, socioeconomic, or other factors) in the study protocol.

▸ Adding Food and Drug Administration postapproval studies and coverage with evidence development (CED) to studies that would qualify under this policy.

▸ Paying for investigational clinical services if they are covered by Medicare outside the trial or required under CED through the national coverage determination (NCD) process.

▸ Expanding the agencies that can deem whether a trial has met the general policy standards to include all Department of Health and Human Services agencies, the Veterans Administration, and the Department of Defense.

The 30-day public commentary period began in April. The CMS will review all public comments and suggestions and incorporate them into the final published NCD no later than 60 days after the end of the comment period, and the revised policy will be effective with that publication.

The Clinical Trial Policy (to be renamed the Clinical Research Policy) was first developed in 2000 to allow Medicare to pay for certain items and services for Medicare beneficiaries involved in clinical trials.

Further details are available from the CMS coverage Web site at www.cms.hhs.gov/mcd/viewdraftdecisionmemo.asp?id=186